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Diabetes and Psychiatry

Integrating Electronic Health Records and Polygenic Risk to Identify Genetically Unrelated Comorbidities of Schizophrenia That May Be Modifiable
Vessels T, Strayer N, Lee H, Choi KW, Zhang S, Han L, Morley TJ, Smoller JW, Xu Y and Ruderfer DM
Patients with schizophrenia have substantial comorbidity that contributes to reduced life expectancy of 10 to 20 years. Identifying modifiable comorbidities could improve rates of premature mortality. Conditions that frequently co-occur but lack shared genetic risk with schizophrenia are more likely to be products of treatment, behavior, or environmental factors and therefore are enriched for potentially modifiable associations.
Obesity in U.S. low-income veterans:Prevalence, clinical characteristics, and homelessness
Stefanovics EA, Potenza MN and Tsai J
Obesity is associated with lower socioeconomic status. To date, however, scarce research has examined the prevalence, comorbidity, and incremental burden of obesity in relation to medical, psychiatric, functional, and homelessness measures among low-income veterans.
Atherosclerosis and depression: is carotid intima-media thicker in patients with depression compared to matched control individuals? A systematic review and meta-analysis
Saleh C, Ilia TS, Schöpfer R, Seidl U, Deraita J, Todua-Lennigk S, Lieb J, Budincevic H, Trzcinska M, Hovhannisyan K, Boviatsis KA and Saleh FM
To investigate if there is an association between atherosclerosis and depression by using as imaging biomarker the carotid intima media thickness (cIMT), a surrogate marker for atherosclerosis.
Type 2 diabetes and health-related quality of life among older Medicare beneficiaries: The mediating role of sleep
Narcisse MR, McElfish PA, Schootman M, Selig JP, Kirkland T, McFarlane SI, Felix HC, Seixas A and Jean-Louis G
To examine mediating effects of sleep quality and duration on the association between T2D and QoL among Medicare beneficiaries 65+.
Associations Between Age at Menopause, Vascular Risk, and 3-Year Cognitive Change in the Canadian Longitudinal Study on Aging
Wood Alexander M, Wu CY, Coughlan GT, Puri T, Buckley RF, Palta P, Swardfager W, Masellis M, Galea LAM, Einstein G, Black SE and Rabin JS
Mounting evidence supports sex differences in Alzheimer disease (AD) risk. Vascular and hormonal factors may together contribute to AD risk in female adults. We investigated whether age at menopause, vascular risk, and history of hormone therapy (HT) containing estrogens together influence cognition over a 3-year follow-up period. We hypothesized that earlier menopause and elevated vascular risk would have a synergistic association with lower cognitive scores at follow-up and that HT containing estrogens would attenuate this synergistic association to preserve cognition.
Healthcare Utilization and Its Correlates in Comorbid Type 2 Diabetes Mellitus and Generalized Anxiety Disorder
Huang CJ, Lin CH, Liu TL, Lin PC, Chu CC, Wang JJ, Wei CW and Weng SF
This study investigated the healthcare utilization and medical expenditure of type 2 diabetes mellitus (T2DM) patients with generalized anxiety disorder (GAD) and identified the associated factors. The healthcare utilization and expenditure of T2DM patients with (case group) and without (control group) GAD between 2002 and 2013 were examined using the population-based Taiwan National Health Insurance Research Database. Healthcare utilization included outpatient visits and hospitalization; health expenditure included outpatient, inpatient, and total medical expenditure. Moreover, nonpsychiatric healthcare utilization and medical expenditure were distinguished from total healthcare utilization and medical expenditure. The average healthcare utilization, including outpatient visits and hospitalization, was significantly higher for the case group than for the control group (total and nonpsychiatric). The results regarding differences in average outpatient expenditure (total and nonpsychiatric), inpatient expenditure (total and nonpsychiatric), and total expenditure (total and nonpsychiatric) between the case and control groups are inconsistent. Sex, age, income, comorbidities/complications, and the diabetes mellitus complication severity index were significantly associated with outpatient visits, medical expenditure, and hospitalization in the case group (total and nonpsychiatric). Greater knowledge of factors affecting healthcare utilization and expenditure in comorbid individuals may help healthcare providers intervene to improve patient management and possibly reduce the healthcare burden in the future.
Kidney and Cardiovascular Effectiveness of Empagliflozin Compared to Dipeptidyl Peptidase-4 Inhibitors in Patients with Type 2 Diabetes
Edmonston D, Mulder H, Lydon E, Chiswell K, Lampron Z, Shay C, Marsolo K, Jones WS, Butler J, Shah RC, Chamberlain AM, Ford DE, Gordon HS, Hwang W, Chang A, Rao A, Bosworth HB and Pagidipati N
Placebo-controlled trials of sodium-glucose cotransporter-2 inhibitors (SGLT2i) demonstrate kidney and cardiovascular benefits for people with type 2 diabetes (T2D) and chronic kidney disease (CKD). We used real-world data to compare the kidney and cardiovascular effectiveness of empagliflozin to dipeptidyl peptidase-4 inhibitors (DPP4i), a commonly prescribed antiglycemic medication, in a diverse population with and without CKD. Using electronic health record data from 20 large US health systems, we leveraged propensity overlap weighting to compare outcomes for empagliflozin and DPP4i initiators with T2D between 2016 and 2020. The primary composite kidney outcome included 40% estimated glomerular filtration rate (eGFR) decline, incident end-stage kidney disease (ESKD), or all-cause mortality through 2 years or censoring. We also assessed cardiovascular and safety outcomes. Among 62,197 new users, 20,279 initiated empagliflozin, and 41,918 initiated DPP4i. Over a median follow-up of 1.1 years, empagliflozin prescription was associated with a lower risk of the primary outcome (HR 0.75, 95% CI 0.65-0.87) compared with DPP4i. Risks for mortality (HR 0.76, 95% CI 0.62-0.92) and a cardiovascular composite of stroke, myocardial infarction, or all-cause mortality (HR 0.81, 95% CI 0.70-0.95) were also lower for empagliflozin initiators. No difference in heart failure hospitalization risk between groups was observed. Genital mycotic infections were more common in patients prescribed empagliflozin (HR 1.72, 95% CI 1.58 - 1.88). Empagliflozin was associated with a lower risk of the primary outcome in patients with CKD (HR 0.68, 95% CI 0.53-0.88) and those without CKD (HR 0.79, 95% CI 0.67 - 0.94). In conclusion, initiation of empagliflozin was associated with a significantly lower risk of kidney and cardiovascular outcomes compared with DPP4i over a median of just over 1 year. The association with a lower risk for clinical outcomes was apparent even for people without known CKD at baseline.
Improving support for university students with type 1 diabetes
Stoet G, Foster E, Kerr C, Jiang L, Thornhill MA, Cyranka K, Matejko B, Sarna-Palacz D, Płonka-Stępień M and Klupa T
Dysregulation of interleukin-8 is involved in the onset and relapse of schizophrenia: An independent validation and meta-analysis
Yan J, Xia Q, Sun X, Yang P, Gao H, Pan Z, Gao J, Zhang L, Wang M, Wang K, Li C, Zhang X, Ju P and Zhu C
As a major mental health disorder, symptoms of schizophrenia (SCZ) include delusions, reduced motivation, hallucinations, reduced motivation and a variety of cognitive disabilities. Many of these symptoms are now known to be associated with abnormal regulation of the immune system. Low blood levels of cytokines and chemokines have been suggested to be one of the underlying causes of SCZ. However, their biological roles at different stages of SCZ remain unclear. Our objective was to investigate expression patterns of cytokines and chemokines at different stages of onset and relapse in SCZ patients and to conduct an analysis of their relationship to disease progression. We also aimed to identify immune features associated with different disease trajectories in patients with SCZ. Gene set enrichment analysis (GSEA) was used to interrogate the GSE27383 dataset and identify key genes associated with inflammation. These results led us to recruit 36 healthy controls, 40 patients with first-episode psychosis (FEP), and 39 patients with SCZ relapse. Meso Scale Discovery technology was used to independently validate serum levels of 35 cytokines and chemokines. This was followed by a meta-analysis to gain a more comprehensive understanding of the role of interleukin-8 (IL-8/CXCL8) in SCZ. Analysis of the GSE27383 database revealed 3596 genes with distinct expression patterns. A significant portion of these genes were identified as inflammation-related and showed remarkable enrichment in three key pathways: IL17, cytokine-cytokine receptor, and AGE-RAGE signaling in diabetic complications. We observed co-expression of CXCL8 and IL16 within these three pathways. In a subsequent analysis of independently validated samples, a notable discrepancy was detected in the inflammatory status between individuals experiencing FEP and those in relapse. In particular, expression of CXCL8 demonstrated superior predictive capability in FEP and relapsed patients. Notably, results of the meta-analysis confirmed that Chinese and European populations were consistent with the overall results (Z = 4.60, P < 0.001; Z = 3.70, P < 0.001). However, in the American subgroup, there was no significant difference in CXCL8 levels between patients with SCZ compared to healthy controls (Z = 1.09, P = 0.277). Our findings suggest that the inflammatory response in patients with SCZ differs across the different stages, with CXCL8 emerging as a potential predictive factor. Collectively, our data suggest that CXCL8 has the potential to serve as a significant immunological signature of SCZ subtypes. Trial registration: The clinical registration number for this trial is ChiCTR2100045240 (Registration Date: 2021/04/09).
Severe Maternal Morbidity and Mental Health Hospitalizations or Emergency Department Visits
Blackman A, Ukah UV, Platt RW, Meng X, Shapiro GD, Malhamé I, Ray JG, Lisonkova S, El-Chaâr D, Auger N and Dayan N
Severe maternal morbidity (SMM) can have long-term health consequences for the affected mother. The association between SMM and future maternal mental health conditions has not been well studied.
Self-reported chronic conditions and COVID-19 public health measures among Canadian adults: an analysis of the Canadian longitudinal study on aging
De Rubeis V, Griffith LE, Duncan L, Jiang Y, de Groh M and Anderson LN
During the COVID-19 pandemic, public health measures were used to reduce the spread of COVID-19; it is unknown whether people with chronic conditions differentially adhered to public health measures. The objectives of this study were to evaluate the association between chronic conditions and adherence and to explore effect modification by sex, age, and income.
Targeting GLP-1 Receptors to Reduce Nicotine Use Disorder: Preclinical and Clinical Evidence
Herman RJ and Schmidt HD
Nicotine use disorder (NUD) remains a leading cause of preventable death in the U.S. Unfortunately, current FDA-approved pharmacotherapies for smoking cessation have limited efficacy and are associated with high rates of relapse. One major barrier to long-term smoking abstinence is body weight gain during withdrawal. Nicotine withdrawal-induced body weight gain can also lead to development of chronic disease states like obesity and type II diabetes mellitus. Therefore, it is critical to identify novel pharmacotherapies for NUD that decrease relapse and nicotine withdrawal symptoms including body weight gain. Recent studies demonstrate that glucagon-like peptide-1 receptor (GLP-1R) agonists attenuate voluntary nicotine taking and seeking and prevent withdrawal-induced hyperphagia and body weight gain. Emerging evidence also suggests that GLP-1R agonists improve cognitive deficits, as well as depressive- and anxiety-like behaviors, which contribute to smoking relapse during withdrawal. While further studies are necessary to fully characterize the effects of GLP-1R agonists on NUD and understand the mechanisms by which GLP-1R agonists decrease nicotine withdrawal-mediated behaviors, the current literature supports GLP-1R-based approaches to treating NUD.
Gut microbiome predicts cognitive function and depressive symptoms in late life
Kolobaric A, Andreescu C, Jašarević E, Hong CH, Roh HW, Cheong JY, Kim YK, Shin TS, Kang CS, Kwon CO, Yoon SY, Hong SW, Aizenstein HJ, Karim HT and Son SJ
Depression in older adults with cognitive impairment increases progression to dementia. Microbiota is associated with current mood and cognition, but the extent to which it predicts future symptoms is unknown. In this work, we identified microbial features that reflect current and predict future cognitive and depressive symptoms. Clinical assessments and stool samples were collected from 268 participants with varying cognitive and depressive symptoms. Seventy participants underwent 2-year follow-up. Microbial community diversity, structure, and composition were assessed using high-resolution 16 S rRNA marker gene sequencing. We implemented linear regression to characterize the relationship between microbiome composition, current cognitive impairment, and depressive symptoms. We leveraged elastic net regression to discover features that reflect current or future cognitive function and depressive symptoms. Greater microbial community diversity associated with lower current cognition in the whole sample, and greater depression in participants not on antidepressants. Poor current cognitive function associated with lower relative abundance of Bifidobacterium, while greater GABA degradation associated with greater current depression severity. Future cognitive decline associated with lower cognitive function, lower relative abundance of Intestinibacter, lower glutamate degradation, and higher baseline histamine synthesis. Future increase in depressive symptoms associated with higher baseline depression and anxiety, lower cognitive function, diabetes, lower relative abundance of Bacteroidota, and lower glutamate degradation. Our results suggest cognitive dysfunction and depression are unique states with an overall biological effect detectable through gut microbiota. The microbiome may present a noninvasive readout and prognostic tool for cognitive and psychiatric states.
Comorbid depression among adults with heart failure in Ethiopia: a hospital-based cross-sectional study
Mulugeta H, Sinclair PM and Wilson A
Depression is a common comorbidity in adults with heart failure. It is associated with poor clinical outcomes, including decreased health-related quality of life and increased morbidity and mortality. There is a lack of data concerning the extent of this issue in Ethiopia. Consequently, this study aimed to assess the prevalence of comorbid depression and associated factors among adults living with heart failure in Ethiopia.
Income variability and incident cardiovascular disease in diabetes: a population-based cohort study
Park YM, Baek JH, Lee HS, Elfassy T, Brown CC, Schootman M, Narcisse MR, Ko SH, McElfish PA, Thomsen MR, Amick BC, Lee SS and Han K
Longitudinal change in income is crucial in explaining cardiovascular health inequalities. However, there is limited evidence for cardiovascular disease (CVD) risk associated with income dynamics over time among individuals with type 2 diabetes (T2D).
Assessing We-Disease Appraisals of Health Problems: Development and Validation of the We-Disease Questionnaire
Vogt AJ, Bartels L, Bertschi IC, Mahler F, Grotzer M, Konrad D, Leibundgut K, Rössler J, Bodenmann G and Landolt MA
In couples dealing with health problems, we-disease appraisals can influence dyadic coping strategies to alleviate distress. This study describes the development and validation of a self-report scale to assess we-disease appraisals of health problems. The newly developed We-Disease Questionnaire (WDQ) was administered in three samples: parents of children with type 1 diabetes ( = 240) or cancer ( = 125) and individuals with visual impairment and their partners ( = 216). Reliability was measured by coefficient omega. To assess construct validity, correlations with other measures of individual and dyadic adjustment were examined. Descriptive statistics across all samples were compared. A 4-item version of the WDQ demonstrated good reliability and validity and showed meaningful associations with established scales. We-disease appraisals were highest among parents of children with cancer and lowest among couples with visual impairment. The WDQ is a reliable and valid measure that can be used across different health problems.
Disordered eating in adolescents with type 1 diabetes: risk factors and screening recommendations
Chad-Friedman E, Clary L and Jhe G
Adolescents with Type 1 diabetes (T1D) are at significantly greater risk for disordered eating behaviors compared to their peers without T1D. Given that this is a dangerous and potentially lethal combination, this review aims to support pediatric medical providers in increasing competence in identification, assessment, and prevention of disordered eating behaviors in adolescents with T1D.
Assessing ChatGPT 4.0's test performance and clinical diagnostic accuracy on USMLE STEP 2 CK and clinical case reports
Shieh A, Tran B, He G, Kumar M, Freed JA and Majety P
While there is data assessing the test performance of artificial intelligence (AI) chatbots, including the Generative Pre-trained Transformer 4.0 (GPT 4) chatbot (ChatGPT 4.0), there is scarce data on its diagnostic accuracy of clinical cases. We assessed the large language model (LLM), ChatGPT 4.0, on its ability to answer questions from the United States Medical Licensing Exam (USMLE) Step 2, as well as its ability to generate a differential diagnosis based on corresponding clinical vignettes from published case reports. A total of 109 Step 2 Clinical Knowledge (CK) practice questions were inputted into both ChatGPT 3.5 and ChatGPT 4.0, asking ChatGPT to pick the correct answer. Compared to its previous version, ChatGPT 3.5, we found improved accuracy of ChatGPT 4.0 when answering these questions, from 47.7 to 87.2% (p = 0.035) respectively. Utilizing the topics tested on Step 2 CK questions, we additionally found 63 corresponding published case report vignettes and asked ChatGPT 4.0 to come up with its top three differential diagnosis. ChatGPT 4.0 accurately created a shortlist of differential diagnoses in 74.6% of the 63 case reports (74.6%). We analyzed ChatGPT 4.0's confidence in its diagnosis by asking it to rank its top three differentials from most to least likely. Out of the 47 correct diagnoses, 33 were the first (70.2%) on the differential diagnosis list, 11 were second (23.4%), and three were third (6.4%). Our study shows the continued iterative improvement in ChatGPT's ability to answer standardized USMLE questions accurately and provides insights into ChatGPT's clinical diagnostic accuracy.
Lithium versus anticonvulsants and the risk of physical disorders - Results from a comprehensive long-term nation-wide population-based study emulating a target trial
Kessing LV, Knudsen MB, Rytgaard HCW, Torp-Pedersen C and Berk M
Bipolar disorder is associated with increased rates of many physical disorders, but the effects of medication are unclear. We systematically investigated the associations between sustained use of first line maintenance agents, lithium versus lamotrigine and valproate, and the risk of physical disorders using a nation-wide population-based target trial emulation covering the entire 5.9 million inhabitants in Denmark. We identified two cohorts. Cohort 1: patients with a diagnosis of bipolar disorder prior to first purchase (N = 12.607). Cohort 2: all 156.678 adult patients who had their first ever purchase (since 1995) of either lithium, lamotrigine or valproate between 1997 and 2021 regardless of diagnosis. Main analyses investigated the effect of sustained exposure defined as exposure for all consecutive 6-months periods during a 10-year follow-up. Outcomes included a diagnosis of incident stroke, arteriosclerosis, angina pectoris, myocardial infarction, diabetes mellitus, myxedema, osteoporosis, dementia, Parkinson's disease, chronic kidney disease and cancer (including subtypes). In both Cohorts 1 and 2, there were no systematic statistically significant differences in associations between sustained use of lithium versus lamotrigine and valproate, respectively, and any physical disorder, including subtypes of disorders, except myxedema, for which exposure to lithium increased the absolute risk of myxedema with 7-10 % compared with lamotrigine or valproate. In conclusion, these analyses emulating a target trial of "real world" observational register-based data show that lithium does not increase the risk of developing any kind of physical disorders, except myxedema, which may be a result of detection bias.
Phenomewide Association Study of Health Outcomes Associated With the Genetic Correlates of 25 Hydroxyvitamin D Concentration and Vitamin D Binding Protein Concentration
Kresge HA, Blostein F, Goleva S, Albiñana C, Revez JA, Wray NR, Vilhjálmsson BJ, Zhu Z, McGrath JJ and Davis LK
While it is known that vitamin D deficiency is associated with adverse bone outcomes, it remains unclear whether low vitamin D status may increase the risk of a wider range of health outcomes. We had the opportunity to explore the association between common genetic variants associated with both 25 hydroxyvitamin D (25OHD) and the vitamin D binding protein (DBP, encoded by the gene) with a comprehensive range of health disorders and laboratory tests in a large academic medical center. We used summary statistics for 25OHD and DBP to generate polygenic scores (PGS) for 66,482 participants with primarily European ancestry and 13,285 participants with primarily African ancestry from the Vanderbilt University Medical Center Biobank (BioVU). We examined the predictive properties of PGS, and two scores related to DBP concentration with respect to 1322 health-related phenotypes and 315 laboratory-measured phenotypes from electronic health records. In those with European ancestry: (a) the PGS and PGS scores, and individual SNPs rs4588 and rs7041 were associated with both 25OHD concentration and 1,25 dihydroxyvitamin D concentrations; (b) higher PGS was associated with decreased concentrations of triglycerides and cholesterol, and reduced risks of vitamin D deficiency, disorders of lipid metabolism, and diabetes. In general, the findings for the African ancestry group were consistent with findings from the European ancestry analyses. Our study confirms the utility of PGS and two key variants within the gene (rs4588 and rs7041) to predict the risk of vitamin D deficiency in clinical settings and highlights the shared biology between vitamin D-related genetic pathways a range of health outcomes.
Molecular mechanisms linking type 2 diabetes mellitus and late-onset Alzheimer's disease: A systematic review and qualitative meta-analysis
Lemche E, Killick R, Mitchell J, Caton PW, Choudhary P and Howard JK
Research evidence indicating common metabolic mechanisms through which type 2 diabetes mellitus (T2DM) increases risk of late-onset Alzheimer's dementia (LOAD) has accumulated over recent decades. The aim of this systematic review is to provide a comprehensive review of common mechanisms, which have hitherto been discussed in separate perspectives, and to assemble and evaluate candidate loci and epigenetic modifications contributing to polygenic risk linkages between T2DM and LOAD. For the systematic review on pathophysiological mechanisms, both human and animal studies up to December 2023 are included. For the qualitative meta-analysis of genomic bases, human association studies were examined; for epigenetic mechanisms, data from human studies and animal models were accepted. Papers describing pathophysiological studies were identified in databases, and further literature gathered from cited work. For genomic and epigenomic studies, literature mining was conducted by formalised search codes using Boolean operators in search engines, and augmented by GeneRif citations in Entrez Gene, and other sources (WikiGenes, etc.). For the systematic review of pathophysiological mechanisms, 923 publications were evaluated, and 138 gene loci extracted for testing candidate risk linkages. 3 57 publications were evaluated for genomic association and descriptions of epigenomic modifications. Overall accumulated results highlight insulin signalling, inflammation and inflammasome pathways, proteolysis, gluconeogenesis and glycolysis, glycosylation, lipoprotein metabolism and oxidation, cell cycle regulation or survival, autophagic-lysosomal pathways, and energy. Documented findings suggest interplay between brain insulin resistance, neuroinflammation, insult compensatory mechanisms, and peripheral metabolic dysregulation in T2DM and LOAD linkage. The results allow for more streamlined longitudinal studies of T2DM-LOAD risk linkages.
The psychosocial outcomes of advanced hybrid closed-loop system in children and adolescents with type 1 diabetes
Jalilova A, Pilan BŞ, Demir G, Özbaran B, Balkı HG, Arslan E, Köse SG, Özen S, Darcan Ş and Gökşen D
The study was carried out to determine the psychosocial outcomes of advanced hybrid closed-loop (AHCL) systems in children and adolescents with type 1 diabetes (T1D). Single-center and cohort study with a duration 6 months consisted of 60 children and adolescents with T1D. Standard clinical procedures, including both glycemic indicators, e.g., sensor-measured time within the 70-180 mg/dL range and glycated hemoglobin (HbA1c) levels, and psychosocial metrics were used for data collection. The psychosocial metrics included the Pediatric Quality of Life Inventory (PedsQL) 3.0 Diabetes Module for both children (8-12 years) and parents; the Quality of Life for Youth scale for adolescents (13-18 years); the Strengths and Difficulties Questionnaire (SDQ); the Hypoglycemia Fear Survey for Children (HFS-C); the Revised Child Anxiety and Depression Scale (R-CADS); and AHCLS-specific DTSEQ satisfaction and expectation survey. These metrics were evaluated at the baseline and after 6 months of AHCL use. Of the 60 children and adolescents with T1D for whom the AHCL system was utilized, 41 of them, 23 female and 18 male, completed the surveys. The mean age of the 41 children and adolescents was 12.5 ± 3.2 (min. 6.7, max. 18) years. The time spent within the target glycemic range, i.e., time-in-range (TIR), improved from 76.9 ± 9% at the baseline to 80.4 ± 5% after 6 months of AHCL system use (p = 0.03). Additionally, HbA1c levels reduced from 7.1% ± 0.7% at the baseline to 6.8% ± 0.8% after 6 months of AHCL system use (p = 0.03). The most notable decline in HbA1c was observed in participants with higher baseline HbA1c levels. All patients' HFS-C and AHCL system-specific DTSEQ satisfaction and expectation survey scores were within the normal range at the baseline and remained unchanged during the follow-up period. No significant difference was found in the R-CADS scores of children and adolescents between baseline and after 6 months of AHCL system use. However, there was a significant decrease in the R-CADS scores of the parents. Patients' PedsQL scores were high both at the baseline and after 6 months. The SDQ scores were high at baseline, and there was no significant improvement at the end of 6 months.  Conclusion: This is the first study to investigate in detail the psychosocial outcomes of AHCL system use in T1D patients and their parents. Although state-of-the-art technologies such as AHCL provide patients with more flexibility in their daily lives and information about glucose fluctuations, the AHCL resulted in a TIR above the recommended target range without a change in QOL, HFS-C, SDQ, and R-CADS scores. The scores obtained from the R-CADS conducted by the parents of the children indicated that the use of pumps caused a psychological improvement in the long term, with a significant decrease in the R-CADS scores of the children and adolescents with T1D. What is Known: • Previous studies focused on clinical outcomes of AHCL systems in pediatric T1D patients, showing glycemic control improvements. • Limited attention given to psychosocial outcomes of AHCL systems in children and adolescents with T1D. • Crucial psychosocial factors like quality of life, emotional well-being, and fear of hypoglycemia underexplored in AHCL system context. What is New: • First study to comprehensively examine psychosocial outcomes of AHCL systems in pediatric T1D patients. • Study's robust methodology sets new standard for diabetes technology research and its impact on qualiy of life.
Intersectional stigma and the non-communicable disease syndemic in the context of HIV: protocol for a multisite, observational study in the USA
Friedman MR, Badri S, Bowleg L, Haberlen SA, Jones DL, Kempf MC, Konkle-Parker D, Kwait J, Martinson J, Mimiaga MJ, Plankey MW, Stosor V, Tsai AC, Turan JM, Ware D and Wu K
The increasing burden of non-communicable diseases, such as hypertension, diabetes and dyslipidaemia, presents key challenges to achieving optimal HIV care outcomes among ageing people living with HIV. These diseases are often comorbid and are exacerbated by psychosocial and structural inequities. This interaction among multiple health conditions and social factors is referred to as a syndemic. In the USA, there are substantial disparities by social position (ie, racial, ethnic and socioeconomic status) in the prevalence and/or control of non-communicable diseases and HIV. Intersecting stigmas, such as racism, classism and homophobia, may drive these health disparities by contributing to healthcare avoidance and by contributing to a psychosocial syndemic (stress, depression, violence victimisation and substance use), reducing success along the HIV and non-communicable disease continua of care. Our hypothesis is that marginalised populations experience disparities in non-communicable disease incidence, prevalence and control, mediated by intersectional stigma and the psychosocial syndemic.
Continuous alcohol withdrawal delirium and physical illness-associated delirium in a man brought to the emergency department after a disaster: A case report
Kikuchi K, Hasegawa C, Sasaki T, Sato Y, Owada T, Shindo Y, Kawamata Y, Sugawara N and Yasui-Furukori N
Risk factors for alcohol withdrawal delirium include heavy drinking, prior alcohol withdrawal delirium or convulsions, nondrug sedative use, and a history of tachycardia, withdrawal, and infections.
Outcomes of long-acting injectable antipsychotics use in pregnancy: A literature review
Pejčić AV, Stefanović SM, Milosavljević MN, Janjić VS, Folić MM, Folić ND and Milosavljević JZ
Women with a history of serious psychotic disorders are at increased risk of disease relapse during pregnancy. Long-acting injectable (LAI) antipsychotics have been widely used to improve adherence and prevent relapse in patients with various severe psychotic disorders, but there is a lack of high-quality data from previous research on the safety of LAI antipsychotics during pregnancy.
Comparing targeted memory reactivation during slow wave sleep and sleep stage 2
Carbone J, Bibian C, Born J, Forcato C and Diekelmann S
Sleep facilitates declarative memory consolidation, which is assumed to rely on the reactivation of newly encoded memories orchestrated by the temporal interplay of slow oscillations (SO), fast spindles and ripples. SO as well as the number of spindles coupled to SO are more frequent during slow wave sleep (SWS) compared to lighter sleep stage 2 (S2). But, it is unclear whether memory reactivation is more effective during SWS than during S2. To test this question, we applied Targeted Memory Reactivation (TMR) in a declarative memory design by presenting learning-associated sound cues during SWS vs. S2 in a counterbalanced within-subject design. Contrary to our hypothesis, memory performance was not significantly better when cues were presented during SWS. Event-related potential (ERP) amplitudes were significantly higher for cues presented during SWS than S2, and the density of SO and SO-spindle complexes was generally higher during SWS than during S2. Whereas SO density increased during and after the TMR period, SO-spindle complexes decreased. None of the parameters were associated with memory performance. These findings suggest that the efficacy of TMR does not depend on whether it is administered during SWS or S2, despite differential processing of memory cues in these sleep stages.
The Association Between Unintended Pregnancy and Perinatal Outcomes in Low-Risk Pregnancies: A Retrospective Registry Study in the Netherlands
van Tintelen AMG, Jansen DEMC, Bolt SH, Warmelink JC, Verhoeven CJ and Henrichs J
People with unintended pregnancies might be at increased risk of adverse perinatal outcomes due to structural factors, distress, or delayed prenatal care. Existing studies addressing this association yielded inconsistent findings. Using contemporary data from a large Dutch midwifery care registry, we investigated the association between unintended pregnancy ending in birth and neonatal outcomes, parental morbidity, and obstetric interventions. We extend previous research by exploring whether delayed initiation of prenatal care mediates these associations.
Global incidence, prevalence, years lived with disability (YLDs), disability-adjusted life-years (DALYs), and healthy life expectancy (HALE) for 371 diseases and injuries in 204 countries and territories and 811 subnational locations, 1990-2021: a systematic analysis for the Global Burden of Disease Study 2021
Detailed, comprehensive, and timely reporting on population health by underlying causes of disability and premature death is crucial to understanding and responding to complex patterns of disease and injury burden over time and across age groups, sexes, and locations. The availability of disease burden estimates can promote evidence-based interventions that enable public health researchers, policy makers, and other professionals to implement strategies that can mitigate diseases. It can also facilitate more rigorous monitoring of progress towards national and international health targets, such as the Sustainable Development Goals. For three decades, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) has filled that need. A global network of collaborators contributed to the production of GBD 2021 by providing, reviewing, and analysing all available data. GBD estimates are updated routinely with additional data and refined analytical methods. GBD 2021 presents, for the first time, estimates of health loss due to the COVID-19 pandemic.
Effects of Paradoxical Sleep Deprivation on Oxidative Parameters in the Serum and Brain of Mice Submitted to the Animal Model of Hyperglycemia
Rosa JP, Sandrini IG, Possamai-Della T, Aguiar-Geraldo JM, Machado-Laureano ML, Zugno AI, Quevedo J and Valvassori SS
The present study aimed to investigate the effects of paradoxical sleep deprivation (PSD) on behavioral and oxidative stress parameters in the brain and serum of mice submitted to the animal model of hyperglycemia induced by alloxan, mimicking the main symptom of diabetes mellitus (DM). Adults C57BL/6 male and female mice received an injection of alloxan, and ten days later, the animals were submitted to the PSD for 36hr. The animals' behavioral parameters were evaluated in the open-field test. Oxidative stress parameters [Diacetyldichlorofluorescein (DCF), Thiobarbituric acid reactive substances (TBARS), Superoxide dismutase (SOD), and Glutathione] were assessed in the frontal cortex, hippocampus, striatum, and serum. The PSD increased the male and female mice locomotion, but the alloxan's pre-administration prevented the PSD-induced hyperactivity. In addition, the male mice receiving alloxan and submitted to the PSD had elevated latency time in the first quadrant and the number of fecal boli, demonstrating increased anxiety-like behavior. The HPA-axis was hyperactivating in male and female mice pre-administered alloxan and/or PSD-submitted animals. The oxidative stress parameters were also increased in the serum of the animals administered alloxan and/or sleep-deprived mice. Despite alloxan or PSD leading to behavioral or biochemical alterations, the one did not potentiate the other in mice. However, more studies are necessary to identify the link between sleep and hyperglycemia.
Trends in Incidence of Hospitalization for Hypoglycemia and Diabetic Ketoacidosis in Individuals With Type 1 or Type 2 Diabetes With and Without Severe Mental Illness in Denmark From 1996 to 2020: A Nationwide Study
Scheuer SH, Andersen GS, Carstensen B, Diaz L, Kosjerina V, Lindekilde N, Wild SH, Jackson CA, Pouwer F, Benros ME and Jørgensen ME
To examine trends in incidence of acute diabetes complications in individuals with type 1 or type 2 diabetes with and without severe mental illness (SMI) in Denmark by age and calendar year.
The role of immuno-metabolic depression features in the effects of light therapy in patients with depression and type 2 diabetes mellitus: A randomized controlled trial
Vreijling SR, Neuhaus L, Brouwer A, Penninx BWJH, Beekman ATF, Lamers F, Jansen R and Bremmer M
Immuno-metabolic depression (IMD) is proposed to be a form of depression encompassing atypical, energy-related symptoms (AES), low-grade inflammation and metabolic dysregulations. Light therapy may alleviate AES by modulating inflammatory and metabolic pathways. We investigated whether light therapy improves clinical and biological IMD features and whether effects of light therapy on AES or depressive symptom severity are moderated by baseline IMD features. Associations between changes in symptoms and biomarkers were explored.
Adolescent gender dysphoria management: position paper from the Italian Academy of Pediatrics, the Italian Society of Pediatrics, the Italian Society for Pediatric Endocrinology and Diabetes, the Italian Society of Adolescent Medicine and the Italian Society of Child and Adolescent Neuropsychiatry
Calcaterra V, Tornese G, Zuccotti G, Staiano A, Cherubini V, Gaudino R, Fazzi EM, Barbi E, Chiarelli F, Corsello G, Esposito SMR, Ferrara P, Iughetti L, Laforgia N, Maghnie M, Marseglia G, Perilongo G, Pettoello-Mantovani M, Ruggieri M, Russo G, Salerno M, Striano P, Valerio G, Wasniewska M and
In response to the imperative need for standardized support for adolescent Gender Dysphoria (GD), the Italian Academy of Pediatrics, in collaboration with the Italian Society of Pediatrics, the Italian Society for Pediatric Endocrinology and Diabetes, Italian Society of Adolescent Medicine and Italian Society of Child and Adolescent Neuropsychiatry is drafting a position paper. The purpose of this paper is to convey the author's opinion on the topic, offering foundational information on potential aspects of gender-affirming care and emphasizing the care and protection of children and adolescents with GD.
Association of Pregnant Women's Perinatal Depression with Sociodemographic, Anthropometric and Lifestyle Factors and Perinatal and Postnatal Outcomes: A Cross-Sectional Study
Jacovides C, Papadopoulou SK, Pavlidou E, Dakanalis A, Alexatou O, Vorvolakos T, Lechouritis E, Papacosta E, Chrysafi M, Mitsiou M, Mentzelou M, Kosti RI and Giaginis C
In recent decades, the incidence of depression has gradually increased in the general population globally. Depression is also common during gestation and could result in detrimental gestational complications for both the mother and the fetus. The survey presented aimed to evaluate whether pregnant women's perinatal depression could be associated with socio-demographic, anthropometry and lifestyle factors, and perinatal and postnatal outcomes. This is a cross-sectional survey conducted on 5314 pregnant women. Socio-demographic and lifestyle factors were recorded by relevant questionnaires via face-to-face interviews. Anthropometric parameters were measured by qualified personnel. Perinatal depressive symptomatology status was evaluated by Beck's Depression Inventory (BDI-II) questionnaire. Depressive symptoms throughout gestation were found in 35.1% of the enrolled women. Perinatal depression was significantly associated with lower educational and economic level, pre-pregnancy regular smoking and reduced levels of Mediterranean diet adherence levels, a higher prevalence of gestational diabetes and preterm birth, as well as a higher incidence of delivering by caesarean section and abnormal childbirth weight. Perinatal depression was also significantly associated with a higher prevalence of maternal postpartum depression and lower prevalence of exclusive breastfeeding practices, as well as with a higher incidence of childhood asthma. Pregnant women's perinatal depression appears to be associated with various socio-demographic, anthropometry, and lifestyle characteristics and with a higher frequency of several adverse pregnancy complications. The present findings emphasize the importance of pregnant women's perinatal mental health, highlighting the need to develop and apply public strategies and policies for psychological counseling and support of future mothers to minimize probable risk factors that may trigger perinatal depression. Novel well-organized, follow-up surveys of enhanced validity are highly recommended to establish more definitive conclusions.
Diagnosis, Treatment and Long-Term Management of Vitamin B12 Deficiency in Adults: A Delphi Expert Consensus
Obeid R, Andrès E, Češka R, Hooshmand B, Guéant-Rodriguez RM, Prada GI, Sławek J, Traykov L, Ta Van B, Várkonyi T, Reiners K and The Vitamin B Consensus Panelists Group
: Vitamin B12 deficiency can cause variable symptoms, which may be irreversible if not diagnosed and treated in a timely manner. We aimed to develop a widely accepted expert consensus to guide the practice of diagnosing and treating B12 deficiency. : We conducted a scoping review of the literature published in PubMed since January 2003. Data were used to design a two-round Delphi survey to study the level of consensus among 42 experts. : The panelists agreed on the need for educational and organizational changes in the current medical practices for diagnosing and treating B12 deficiency. Recognition of clinical symptoms should receive the highest priority in establishing the diagnosis. There is agreement that the serum B12 concentration is useful as a screening marker and methylmalonic acid or homocysteine can support the diagnosis. Patient lifestyle, disease history, and medications can provide clues to the cause of B12 deficiency. Regardless of the cause of the deficiency, initial treatment with parenteral B12 was regarded as the first choice for patients with acute and severe manifestations of B12 deficiency. The use of high-dose oral B12 at different frequencies may be considered for long-term treatment. Prophylactic B12 supplementation should be considered for specific high-risk groups. : There is a consensus that clinical symptoms need to receive more attention in establishing the diagnosis of B12 deficiency. B12 laboratory markers can support the diagnosis. The severity of clinical symptoms, the causes of B12 deficiency, and the treatment goals govern decisions regarding the route and dose of B12 therapy.
Impact of Long-COVID in children: a large cohort study
Hersh Z, Weisband YL, Bogan A, Leibovich A, Obolski U, Nevo D and Gilad-Bachrach R
The impact of long-term Coronavirus disease 2019 (COVID-19) on the pediatric population is still not well understood. This study was designed to estimate the magnitude of COVID-19 long-term morbidity 3-6 months after the date of diagnosis.
Brain morphometry and estimation of aging brain in subjects with congenital untreated isolated GH deficiency
Villar-Gouy KR, Salmon CEG, Salvatori R, Kellner M, Krauss MPO, Rocha TO, de Souza EA, Batista VO, Leal ÂC, Santos LB, Melo EV, Oliveira-Santos AA, Oliveira CRP, Campos VC, Santos EG, Santana NO, Pereira FA, Amorim RS, Donato-Junior J, Filho JASB, Santos AC and Aguiar-Oliveira MH
Individuals with isolated GH deficiency (IGHD) due to a mutation in the GHRH receptor gene have a normal life expectancy and above 50 years of age, similar total cognitive performance, with better attention and executive function than controls. Our objectives were to evaluate their brain morphometry and brain aging using MRI.
Methods to predict heart failure in diabetes patients
Berezin AE, Berezina TA, Hoppe UC, Lichtenauer M and Berezin AA
Type 2 diabetes mellitus (T2DM) is one of the leading causes of cardiovascular disease and powerful predictor for new-onset heart failure (HF).
Depressive disorder and elevated risk of bell's palsy: a nationwide propensity score-weighting study
Fann LY, Wen YL, Huang YC, Cheng CC, Huang YC, Fang CC, Chen WT, Yu PY, Pan HY and Kao LT
Prior studies have reported a potential relationship between depressive disorder (DD), immune function, and inflammatory response. Some studies have also confirmed the correlation between immune and inflammatory responses and Bell's palsy. Considering that the pathophysiology of these two diseases has several similarities, this study investigates if DD raises the risk of developing Bell's palsy.
PPAR agonists as add-on treatment with metformin in management of type 2 diabetes: a systematic review and meta-analysis
Alnuaimi S, Reljic T, Abdulla FS, Memon H, Al-Ali S, Smith T, Serdarevic F, Velija Asimi Z, Kumar A and Semiz S
The combination of metformin and the peroxisome proliferator-activated receptors (PPAR) agonists offers a promising avenue for managing type 2 diabetes (T2D) through their potential complementary mechanisms of action. The results from randomized controlled trials (RCT) assessing the efficacy of PPAR agonists plus metformin versus metformin alone in T2D are inconsistent, which prompted the conduct of the systematic review and meta-analysis. We searched MEDLINE and EMBASE from inception (1966) to March 2023 to identify all RCTs comparing any PPAR agonists plus metformin versus metformin alone in T2D. Categorical variables were summarized as relative risk along with 95% confidence interval (CI). Twenty RCTs enrolling a total of 6058 patients met the inclusion criteria. The certainty of evidence ranged from moderate to very low. Pooled results show that using PPAR agonist plus metformin, as compared to metformin alone, results in lower concentrations of fasting glucose [MD = - 22.07 mg/dl (95% CI - 27.17, - 16.97), HbA1c [MD = - 0.53% (95% CI - 0.67, - 0.38)], HOMA-IR [MD = - 1.26 (95% CI - 2.16, - 0.37)], and fasting insulin [MD = - 19.83 pmol/L (95% CI - 29.54, - 10.13)] without significant increase in any adverse events. Thus, synthesized evidence from RCTs demonstrates the beneficial effects of PPAR agonist add-on treatment versus metformin alone in T2D patients. In particular, novel dual PPARα/γ agonist (tesaglitazar) demonstrate efficacy in improving glycaemic and lipid concentrations, so further RCTs should be performed to elucidate the long-term outcomes and safety profile of these novel combined and personalized therapeutic strategies in the management of T2D.PROSPERO registration no. CRD42023412603.
Disordered eating behaviors in gender-affirmative treatment seeking transgender people
Usta Sağlam NG, Zengin K, Osmanlı Shirolu S, Sulu C, Kırpınar MM and Turan Ş
This study aimed to explore disordered eating behaviors in gender-affirming treatment (GAT)-seeking transgender (TG) adults and cisgender people, in addition to analyzing the association between gender dysphoria intensity, body mass index, and disordered eating behaviors. Data were collected from 132 GAT-seeking TG people with gender dysphoria who had never received GAT (91 TG men, 41 TG women), and 153 cisgender (99 cisgender men, 54 cisgender women) participants from Turkey. The Utrecht Gender Dysphoria Scale was used to evaluate the intensity of gender dysphoria. Eating Disorder Examination Questionnaire and Questionnaire on Eating and Weight Patterns-5 were utilized to assess disordered eating. There was no difference between TG women and TG men in terms of ED psychopathology. The most prominent characteristic in all four groups was shape concern, which was significantly higher in TG men and TG women when compared to cisgender men and cisgender women. Binge eating was notably more frequent in TG men and TG women compared to cisgender men, with 11% of the TG men and 7.3% of the TG women meeting the criteria for possible binge eating disorder. Screening for disordered eating behaviors, particularly binge eating, may be recommended in routine care for TG people.
DNA methylation-based telomere length is associated with HIV infection, physical frailty, cancer, and all-cause mortality
Liang X, Aouizerat BE, So-Armah K, Cohen MH, Marconi VC, Xu K and Justice AC
Telomere length (TL) is an important indicator of cellular aging. Shorter TL is associated with several age-related diseases including coronary heart disease, heart failure, diabetes, osteoporosis, and cancer. Recently, a DNA methylation-based TL (DNAmTL) estimator has been developed as an alternative method for directly measuring TL. In this study, we examined the association of DNAmTL with cancer prevalence and mortality risk among people with and without HIV in the Veterans Aging Cohort Study Biomarker Cohort (VACS, N = 1917) and Women's Interagency HIV Study Cohort (WIHS, N = 481). We profiled DNAm in whole blood (VACS) or in peripheral blood mononuclear cells (WIHS) using an array-based method. Cancer prevalence was estimated from electronic medical records and cancer registry data. The VACS Index was used as a measure of physiologic frailty. Models were adjusted for self-reported race and ethnicity, batch, smoking status, alcohol consumption, and five cell types (CD4, CD8, NK, B cell, and monocyte). We found that people with HIV had shorter average DNAmTL than those without HIV infection [beta = -0.25, 95% confidence interval (-0.32, -0.18), p = 1.48E-12]. Greater value of VACS Index [beta = -0.002 (-0.003, -0.001), p = 2.82E-05] and higher cancer prevalence [beta = -0.07 (-0.10, -0.03), p = 1.37E-04 without adjusting age] were associated with shortened DNAmTL. In addition, one kilobase decrease in DNAmTL was associated with a 40% increase in mortality risk [hazard ratio: 0.60 (0.44, 0.82), p = 1.42E-03]. In summary, HIV infection, physiologic frailty, and cancer are associated with shortening DNAmTL, contributing to an increased risk of all-cause mortality.
Genital Surgery Outcomes Using an Individualized Algorithm for Hormone Management in Transfeminine Individuals
Herndon J, Gupta N, Davidge-Pitts C, Imhof N, Gonzalez C, Carlson S, Will M, Martinez-Jorge J, Fahradyan V, Tamire L, Lin A, Nippoldt TB and Chang AY
Transgender and gender diverse (TGD) individuals have greater access to genital surgery (GS) with improved insurance coverage and access to trained surgeons and interdisciplinary gender affirming providers.
A randomised controlled trial to evaluate the effectiveness of a culture and disease-specific, patient-centric multi-component tobacco cessation intervention package for the patients attending non-communicable disease clinics in Punjab, India
Bhatt G, Goel S, Yadav SK, Patial A, Medhi B, Grover S, Attri S, Kaur R, Singh G and Gill SS
Developing an infrastructure to support tobacco cessation through existing systems and resources is crucial for ensuring the greatest possible access to cessation services. The present study aims to evaluate the effectiveness of a newly developed multi-component cessation among tobacco users in Non- Communicable Disease (NCD) clinics, functioning under the National Programme for Prevention & Control of Cancer, Diabetes, Cardiovascular Diseases, & Stroke (NPCDCS) of the Government of India.
Putting a label on someone: impact of schizophrenia stigma on emotional mimicry, liking, and interpersonal closeness
Parisi M, Raffard S, Slangen P, Kastendieck T, Hess U, Mauersberger H, Fauviaux T and Marin L
Affiliation is both an antecedent and a consequence of emotional mimicry (i.e. imitating a counterpart's emotional expression). Thus, interacting with a disliked partner can decrease emotional mimicry, which in turn can further decrease liking. This perpetuating circle has not been investigated in the context of mental health stigma yet. The present study tested the influence of the label "schizophrenia" on liking, interpersonal closeness, and emotional mimicry. In an online experiment ( = 201), participants recruited from the general population saw several videos of actors displaying emotional expressions. Actors were described with one of four labels: "schizophrenia", "healthy", "diabetes", and a negative adjective (e.g. "hot-tempered"). Emotional mimicry was measured using OpenFace 2.2. Liking and interpersonal closeness were assessed with questionnaires. Overall, compared to other labels, participants reported less liking and interpersonal closeness to the actor with the schizophrenia label. However, no effect on emotional mimicry was found. The decreased liking of the schizophrenia actors was explained by a lack of knowledge about schizophrenia and the explicit stigma of schizophrenia. Our study contributes to the literature by highlighting the need to reduce the stigma of schizophrenia.
Subclinical Metabolic and Cardiovascular Factors and Brain White Matter Microstructural Integrity in Young Women
McBride CA, Russom Z, Bernstein IM and Dumas JA
Women who have experienced pregnancy complications, specifically preeclampsia and gestational diabetes, have well documented increased risks of cardiovascular, metabolic, and neurological disease later in life. This study examined how specific cardiovascular and metabolic risk factors for preeclampsia assessed in a non-pregnant state were associated with brain white matter microstructural integrity. This study examined sixty-two healthy women (mean age 31 ± 5 years) who received metabolic and cardiovascular assessments as well as multiple modality MRI imaging. Participants were either nulliparous (n = 31) or had a history of preterm preeclampsia (n = 31). Imaging included acquisition Diffusion Tensor Imaging (DTI) to assess white matter integrity within the brain. We hypothesized that healthy, young, non-pregnant women with cardiovascular and metabolic profiles suggesting elevated risk would have decreased white matter integrity, represented by lower Fractional Anisotropy (FA) and increased Mean Diffusivity (MD) estimates in the posterior cortical areas of the brain. We observed increased white matter degradation (lower FA and increased MD) in posterior and occipital tracts, commissural fibers, and subcortical structures in women with increased adiposity, worse measures of cardiovascular and metabolic function, including greater insulin resistance (HOMA-IR), hyperlipidemia, elevated blood pressure, and increased arterial stiffness. The relationships detected between subclinical cardiovascular and metabolic phenotypes and increased white matter disruption at a young age, outside of pregnancy, are indicative that adverse changes are detectable long before cognitive clinical presentation. This may suggest that many of the long-term cardiovascular and metabolic risks of aging are influenced by physiologic aging trajectories rather than damage caused by pregnancy complications.
Gestational age at birth and type 1 diabetes in childhood and young adulthood: a nationwide register study in Finland, Norway and Sweden
Metsälä J, Risnes K, Persson M, Veijola R, Pulakka A, Heikkilä K, Alenius S, Gissler M, Opdahl S, Sandin S and Kajantie E
Children and adults born preterm have an increased risk of type 1 diabetes. However, there is limited information on risk patterns across the full range of gestational ages, especially after extremely preterm birth (23-27 weeks of gestation). We investigated the risk of type 1 diabetes in childhood and young adulthood across the full range of length of gestation at birth.
Risk of depression and anxiety in multiple sclerosis and neuromyelitis optica spectrum disorder: A nationwide cohort study in South Korea
Kwon S, Han KD, Jung JH, Cho EB, Chung YH, Park J, Choi HL, Jeon HJ, Shin DW and Min JH
We investigated the risks of depression/anxiety in patients with multiple sclerosis (pwMS) or patients with neuromyelitis optica spectrum disorder (pwNMOSD).
Maternal diabetes and risk of attention-deficit/hyperactivity disorder in offspring in a multinational cohort of 3.6 million mother-child pairs
Chan AYL, Gao L, Hsieh MH, Kjerpeseth LJ, Avelar R, Banaschewski T, Chan AHY, Coghill D, Cohen JM, Gissler M, Harrison J, Ip P, Karlstad Ø, Lau WCY, Leinonen MK, Leung WC, Liao TC, Reutfors J, Shao SC, Simonoff E, Tan KCB, Taxis K, Tomlin A, Cesta CE, Lai EC, Zoega H, Man KKC and Wong ICK
Previous studies report an association between maternal diabetes mellitus (MDM) and attention-deficit/hyperactivity disorder (ADHD), often overlooking unmeasured confounders such as shared genetics and environmental factors. We therefore conducted a multinational cohort study with linked mother-child pairs data in Hong Kong, New Zealand, Taiwan, Finland, Iceland, Norway and Sweden to evaluate associations between different MDM (any MDM, gestational diabetes mellitus (GDM) and pregestational diabetes mellitus (PGDM)) and ADHD using Cox proportional hazards regression. We included over 3.6 million mother-child pairs between 2001 and 2014 with follow-up until 2020. Children who were born to mothers with any type of diabetes during pregnancy had a higher risk of ADHD than unexposed children (pooled hazard ratio (HR) = 1.16, 95% confidence interval (CI) = 1.08-1.24). Higher risks of ADHD were also observed for both GDM (pooled HR = 1.10, 95% CI = 1.04-1.17) and PGDM (pooled HR = 1.39, 95% CI = 1.25-1.55). However, siblings with discordant exposure to GDM in pregnancy had similar risks of ADHD (pooled HR = 1.05, 95% CI = 0.94-1.17), suggesting potential confounding by unmeasured, shared familial factors. Our findings indicate that there is a small-to-moderate association between MDM and ADHD, whereas the association between GDM and ADHD is unlikely to be causal. This finding contrast with previous studies, which reported substantially higher risk estimates, and underscores the need to reevaluate the precise roles of hyperglycemia and genetic factors in the relationship between MDM and ADHD.
Psychiatric disorders in pregnant women admitted to the high-risk obstetric service in a Colombian university clinic between 2013 and 2017
Constaín GA, Ocampo Saldarriaga MV, Franco Vásquez JGF, Naranjo LF, Restrepo Conde C, Estrada Muñoz D, Chaverra López L and Buriticá González JB
To determine the psychiatric diagnoses and treatments of patients admitted to the high-risk obstetric service who underwent a consultation with a liaison psychiatrist.
Time-varying associations of gestational and childhood triclosan with pubertal and adrenarchal outcomes in early adolescence
Laue HE, Lanphear BP, Calafat AM, Cecil KM, Chen A, Xu Y, Kalkwarf HJ, Madan JC, Karagas MR, Yolton K, Fleisch AF and Braun JM
Triclosan is an endocrine-disrupting chemical, but associations with pubertal outcomes remain unclear. We examined associations of gestational and childhood triclosan with adolescent hormone concentrations and pubertal stage.
Perturbation of the insomnia WDR90 GWAS locus pinpoints rs3752495 as a causal variant influencing distal expression of neighboring gene, PIG-Q
Sonti S, Littleton SH, Pahl MC, Zimmerman AJ, Chesi A, Palermo J, Lasconi C, Brown EB, Pippin JA, Wells AD, Doldur-Balli F, Pack AI, Gehrman PR, Keene AC and Grant SFA
Although genome wide association studies (GWAS) have identified loci for sleep-related traits, they do not directly uncover the underlying causal variants and corresponding effector genes. The majority of such variants reside in non-coding regions and are therefore presumed to impact cis-regulatory elements. Our previously reported 'variant-to-gene mapping' effort in human induced pluripotent stem cell (iPSC)-derived neural progenitor cells (NPCs), combined with validation in both Drosophila and zebrafish, implicated PIG-Q as a functionally relevant gene at the insomnia 'WDR90' GWAS locus. However, importantly that effort did not characterize the corresponding underlying causal variant. Specifically, our previous 3D genomic datasets nominated a shortlist of three neighboring single nucleotide polymorphisms (SNPs) in strong linkage disequilibrium within an intronic enhancer region of WDR90 that contacted the open PIG-Q promoter. We sought to investigate the influence of these SNPs collectively and then individually on PIG-Q modulation to pinpoint the causal "regulatory" variant. Starting with gross level perturbation, deletion of the entire region in NPCs via CRISPR-Cas9 editing and subsequent RNA sequencing revealed expression changes in specific PIG-Q transcripts. Results from individual luciferase reporter assays for each SNP in iPSCs revealed that the region with the rs3752495 risk allele induced a ~2.5-fold increase in luciferase expression. Importantly, rs3752495 also exhibited an allele specific effect, with the risk allele increasing the luciferase expression by ~2-fold versus the non-risk allele. In conclusion, our variant-to-function approach and in vitro validation implicates rs3752495 as a causal insomnia variant embedded within WDR90 while modulating the expression of the distally located PIG-Q.
The role of peer social relationships in psychological distress and quality of life among adolescents with type 1 diabetes mellitus: a longitudinal study
Luo D, Cai X, Wang H, Wang Y and Xu J
Adolescents with type 1 diabetes mellitus suffer from diabetes distress and poor health-related quality of life (HRQOL) since living with the condition that differentiates them from their peers. The present study investigated the effects of peer support and stress on diabetes distress and HRQOL and whether positive coping mediated the effects.
Antidepressant treatment and mortality in people with comorbid depression and type 2 diabetes: UK electronic health record study
Jeffery A, Walters K, Wong ICK, Osborn D and Hayes JF
Depression is associated with higher rates of premature mortality in people with physical comorbidities, such as type 2 diabetes. Conceptually, the successful treatment of depression in people with type 2 diabetes could prevent premature mortality.
Association between white matter hyperintensity and anxiety/depression
Zhou R, Cai Q, Liu C, Hui J, Kang M, Gou Y, Liu Y, Shi P, Wang B and Zhang F
Although previous studies have explored the associations of white matter hyperintensity with psychiatric disorders, the sample size is small and the conclusions are inconsistent. The present study aimed to further systematically explore the association in a larger sample. All data were extracted from the UK Biobank. First, general linear regression models and logistic regression models were used to assess the association between white matter hyperintensity volume and anxiety/depression. White matter hyperintensity has been classified into periventricular white matter hyperintensity and deep white matter hyperintensity. Anxiety was determined by General Anxiety Disorder-7 score (n = 17,221) and self-reported anxiety (n = 15,333), depression was determined by Patient Health Questionnaire-9 score (n = 17,175), and self-reported depression (n = 14,519). Moreover, we employed Cox proportional hazard models to explore the association between white matter hyperintensity volume and anxiety/depression. The covariates included in fully adjusted model are age, gender, body mass index, Townsend deprivation index, healthy physical activity, cigarette consumption, alcohol consumption, educational attainment, diabetes, hypertension, and coronary heart disease. The results of the fully adjusted model showed that white matter hyperintensity volume was significantly associated with General Anxiety Disorder-7 score (periventricular white matter hyperintensity: β = 0.152, deep white matter hyperintensity: β = 0.094) and Patient Health Questionnaire-9 score (periventricular white matter hyperintensity: β = 0.168). Logistic regression analysis results indicated that periventricular white matter hyperintensity volume (odds ratio = 1.153) was significantly associated with self-reported anxiety. After applying the Cox proportional hazard models, we found that larger white matter hyperintensity volume was associated with increased risk of depression (periventricular white matter hyperintensity: hazard ratio = 1.589, deep white matter hyperintensity: hazard ratio = 1.200), but not anxiety. In summary, our findings support a positive association between white matter hyperintensity volume and depression.
National Cohort Data Suggests an Association Between Serious Mental Illness and Audiometric Hearing Loss
Alter IL, Tucker LH, Dragon JM, Grewal MR, Saperstein A, Stroup TS, Medalia AA and Golub JS
To explore whether there is an association between serious mental illness (SMI) and hearing loss (HL) among US Hispanic adults.
Liraglutide 3.0 mg once daily for the treatment of overweight and obesity in patients hospitalised at a forensic psychiatric department: A 26-week open-label feasibility study
Sass MR, Christensen AMB, Christensen ML, Gruber E, Nerdrum H, Pedersen LM, Resch M, Jørgensen TH, Ekstrøm CT, Nielsen J, Vilsbøll T and Fink-Jensen A
Overweight and obesity constitute a major concern among patients treated at forensic psychiatric departments. The present clinical feasibility study aimed at investigating the extent to which glucagon-like peptide 1 receptor agonist (GLP-1RA) treatment with once-daily liraglutide 3.0 mg could be a feasible pharmacological treatment of these conditions in patients with schizophrenia spectrum disorders hospitalised in forensic psychiatry.
Parent, child, and adolescent lived experience using the insulin-only iLet Bionic Pancreas
Howard KR, Garza KP, Feldman M and Weissberg-Benchell J
Automated insulin delivery (AID) systems show great promise for improving glycemic outcomes and reducing disease burden for youth with type 1 diabetes (T1D). The current study examined youth and parent perspectives after using the insulin-only iLet Bionic Pancreas (BP) during the 13-week pivotal trial.
Anxiety and depression symptoms in adolescents and young adults with juvenile idiopathic arthritis: results of an outpatient screening
Milatz F, Klotsche J, Niewerth M, Sengler C, Windschall D, Kallinich T, Dressler F, Trauzeddel R, Holl RW, Foeldvari I, Brück N, Temming S, Hospach T, Warschburger P, Berendes R, Erbis G, Kuemmerle-Deschner JB, Weller-Heinemann F, Haas JP, Müller-Stierlin AS, Mutter A, Meissner T, Baumeister H and Minden K
Previous studies have shown that growing up with rheumatic conditions can fuel dissatisfaction and psychological distress, which in turn affects disease self-management and treatment adherence. Primary objective of this study was to estimate the prevalence of anxiety and depression symptoms in adolescents and young adults (AYA) with juvenile idiopathic arthritis (JIA) and to identify correlates of conspicuous screening results.
Importance of Prenatal Diagnosis of Ileal Atresia in Gestational Diabetes Cases
Chelu SC, Kundnani NR, Nistor D, Chiriac VD, Brad GF, Cerbu S, Iancu MA and Borza C
BACKGROUND Maldevelopment of the fetal bowel can result in the rare condition of intestinal atresia, which results in congenital bowel obstruction. This report describes a case of prenatal diagnosis of fetal ileal atresia at 22 weeks' gestation. CASE REPORT Here, we present a 24-year old woman who was 22 weeks into her first pregnancy when she underwent routine fetal ultrasound. She was diagnosed with gestational diabetes mellitus. Her body mass index was normal and she had normal weight gain. The ultrasonographic examination performed revealed a hyperechoic bowel and a small dilatation of the bowel. The couple was counselled for possible intestinal atresia and its postnatal implications. At 33 weeks of gestation, polyhydramnios appeared, and the intestinal distension was much more pronounced, with hyperechoic debris in the intestinal lumen (succus-entericus). After birth, surgery was performed and we concluded the patient had type II atresia, which was surgically treated. CONCLUSIONS This report has highlighted the importance of antenatal ultrasound in detecting fetal abnormalities, and has shown that rare conditions such as intestinal atresia can be accurately diagnosed and successfully managed. Surgical correction, if implemented promptly after stabilizing the general condition, can have a relatively good prognosis. Coexisting fetal ileal atresia and gestational diabetes mellitus are rare occurrences, which can make each condition even more difficult to treat.
Development and validation of a machine learning model for prediction of type 2 diabetes in patients with mental illness
Bernstorff M, Hansen L, Enevoldsen K, Damgaard J, Hæstrup F, Perfalk E, Danielsen AA and Østergaard SD
Type 2 diabetes (T2D) is approximately twice as common among individuals with mental illness compared with the background population, but may be prevented by early intervention on lifestyle, diet, or pharmacologically. Such prevention relies on identification of those at elevated risk (prediction). The aim of this study was to develop and validate a machine learning model for prediction of T2D among patients with mental illness.
[Not Available]
Kleinman RA and Selby P
Implementation of an Electronic Clinical Decision Support System for the Early Recognition and Management of Dysglycemia in an Inpatient Mental Health Setting Using CogStack: Protocol for a Pilot Hybrid Type 3 Effectiveness-Implementation Randomized Controlled Cluster Trial
Patel D, Msosa YJ, Wang T, Williams J, Mustafa OG, Gee S, Arroyo B, Larkin D, Tiedt T, Roberts A, Dobson RJB and Gaughran F
Severe mental illnesses (SMIs), including schizophrenia, bipolar affective disorder, and major depressive disorder, are associated with an increased risk of physical health comorbidities and premature mortality from conditions including cardiovascular disease and diabetes. Digital technologies such as electronic clinical decision support systems (eCDSSs) could play a crucial role in improving the clinician-led management of conditions such as dysglycemia (deranged blood sugar levels) and associated conditions such as diabetes in people with a diagnosis of SMI in mental health settings.
Evaluation of the possible impact of the fear of hypoglycemia on diabetes management in children and adolescents with type 1 diabetes mellitus and their parents: a cross-sectional study
Andreopoulou O, Kostopoulou E, Kotanidou E, Daskalaki S, Vakka A, Galli-Tsinopoulou A and Spiliotis BE
Hypoglycemia represents a significant source of anxiety for children with type 1 diabetes mellitus (T1DM) and their caretakers. Fear of hypoglycemia (FoH) was measured in children and adolescents with T1DM as well as in their parents using an established research instrument, the Hypoglycemia Fear Survey (HFS).
Genomic Loci Influencing Cue-Reactivity in Heterogeneous Stock Rats
King CP, Chitre AS, Leal-Gutiérrez JD, Tripi JA, Hughson AR, Horvath AP, Lamparelli AC, George A, Martin C, Pierre CLS, Sanches T, Bimschleger HV, Gao J, Cheng R, Nguyen KM, Holl KL, Polesskaya O, Ishiwari K, Chen H, Woods LCS, Palmer AA, Robinson TE, Flagel SB and Meyer PJ
Addiction vulnerability is associated with the tendency to attribute incentive salience to reward predictive cues; both addiction and the attribution of incentive salience are influenced by environmental and genetic factors. To characterize the genetic contributions to incentive salience attribution, we performed a genome-wide association study (GWAS) in a cohort of 1,645 genetically diverse heterogeneous stock (HS) rats. We tested HS rats in a Pavlovian conditioned approach task, in which we characterized the individual responses to food-associated stimuli ("cues"). Rats exhibited either cue-directed "sign-tracking" behavior or food-cup directed "goal-tracking" behavior. We then used the conditioned reinforcement procedure to determine whether rats would perform a novel operant response for unrewarded presentations of the cue. We found that these measures were moderately heritable (SNP heritability, = .189-.215). GWAS identified 14 quantitative trait loci (QTLs) for 11 of the 12 traits we examined. Interval sizes of these QTLs varied widely. 7 traits shared a QTL on chromosome 1 that contained a few genes () that have been associated with substance use disorders and other mental health traits in humans. Other candidate genes () in this region had coding variants and expression-QTLs in mesocorticolimbic regions of the brain. We also conducted a Phenome-Wide Association Study (PheWAS) on other behavioral measures in HS rats and found that regions containing QTLs on chromosome 1 were also associated with nicotine self-administration in a separate cohort of HS rats. These results provide a starting point for the molecular genetic dissection of incentive salience and provide further support for a relationship between attribution of incentive salience and drug abuse-related traits.
Gut bacteria-driven homovanillic acid alleviates depression by modulating synaptic integrity
Zhao M, Ren Z, Zhao A, Tang Y, Kuang J, Li M, Chen T, Wang S, Wang J, Zhang H, Wang J, Zhang T, Zeng J, Liu X, Xie G, Liu P, Sun N, Bao T, Nie T, Lin J, Liu P, Zheng Y, Zheng X, Liu T and Jia W
The gut-brain axis is implicated in depression development, yet its underlying mechanism remains unclear. We observed depleted gut bacterial species, including Bifidobacterium longum and Roseburia intestinalis, and the neurotransmitter homovanillic acid (HVA) in individuals with depression and mouse depression models. Although R. intestinalis does not directly produce HVA, it enhances B. longum abundance, leading to HVA generation. This highlights a synergistic interaction among gut microbiota in regulating intestinal neurotransmitter production. Administering HVA, B. longum, or R. intestinalis to mouse models with chronic unpredictable mild stress (CUMS) and corticosterone (CORT)-induced depression significantly improved depressive symptoms. Mechanistically, HVA inhibited synaptic autophagic death by preventing excessive degradation of microtubule-associated protein 1 light chain 3 (LC3) and SQSTM1/p62 proteins, protecting hippocampal neurons' presynaptic membrane. These findings underscore the role of the gut microbial metabolism in modulating synaptic integrity and provide insights into potential novel treatment strategies for depression.
Personality traits and the risk of urinary incontinence: Evidence from three longitudinal samples
Stephan Y, Sutin AR and Terracciano A
Urinary incontinence (UI) is a common condition with a substantial negative impact on older adults' quality of life. This study examines whether individual differences in behavioral, cognitive, and emotional traits assessed by the five major dimensions of personality are related to the risk of concurrent and incident UI.
Moderating Effect of Depression on Glycemic Control in an eHealth Intervention Among Black Youth With Type 1 Diabetes: Findings From a Multicenter Randomized Controlled Trial
Ellis D, Carcone AI, Templin T, Evans M, Weissberg-Benchell J, Buggs-Saxton C, Boucher-Berry C, Miller JL, Drossos T and Dekelbab MB
Black adolescents with type 1 diabetes (T1D) are at increased risk for suboptimal diabetes health outcomes; however, evidence-based interventions for this population are lacking. Depression affects a high percentage of youth with T1D and increases the likelihood of health problems associated with diabetes.
Association Between Triglyceride Glucose Index with Cognitive Impairment and Dementia in Adult Population: A Meta-Analysis
Han Y, Meng X and Wang D
The current understanding of the correlation between insulin resistance (IR) and cognitive dysfunction is limited. Therefore, the objective of this systematic review and meta-analysis was to assess the association between the triglyceride glucose (TyG) index, a recently suggested indicator of IR, and cognitive impairment and dementia in the adult population. Observational studies pertinent to our research were identified through comprehensive searches of the PubMed, Embase, and Web of Science databases. To account for potential heterogeneity, the random-effects models were employed to aggregate the findings. This meta-analysis included ten observational studies involving 5602409 participants. Compared to those with the low TyG index, subjects with the high TyG index were significantly associated with the risk of cognitive impairment [risk ratio (RR): 1.39, 95% confidence interval (CI): 1.22 to 1.59, p<0.001; I2=45%) and dementia (RR: 1.30, 95% CI: 1.06 to 1.60, p=0.01; I2=50%). The association was consistent for Alzheimer's disease (RR: 1.35, 95% CI: 1.04 to 1.76, p=0.03; I2=54%) and vascular dementia (RR: 1.18, 95% CI: 1.13 to 1.24, p<0.001; I2=0%). Subgroup analyses showed that the association between TyG index with cognitive impairment and dementia were stronger in cross-sectional studies than that in cohort studies (p for subgroup difference=0.02), but not significantly modified by age, sex, or diabetic status of the participants. In conclusion, a high TyG index may be associated with higher risk of cognitive impartment and dementia in adult population.
An ecological resilience model for adolescents with type 1 diabetes: a cross-sectional study
Luo D, Cai X, Wang H, Xu J, Wang Y and Li M
Highly resilient adolescents with type 1 diabetes have been proved to achieve within-target glycemic outcomes and experience high quality of life. The ecological resilience model for adolescents with type 1 diabetes was developed in this study. It aims to increase our understanding of how resilience is both positively and negatively affected by internal and environmental ecological factors.
CSF biomarkers of immune activation and Alzheimer's disease for predicting cognitive impairment risk in the elderly
Shue F, White LJ, Hendrix R, Ulrich J, Henson RL, Knight W, Martens YA, Wang N, Roy B, Starling SC, Ren Y, Xiong C, Asmann YW, Syrjanen JA, Vassilaki M, Mielke MM, Timsina J, Sung YJ, Cruchaga C, Holtzman DM, Bu G, Petersen RC, Heckman MG and Kanekiyo T
The immune system substantially influences age-related cognitive decline and Alzheimer's disease (AD) progression, affected by genetic and environmental factors. In a Mayo Clinic Study of Aging cohort, we examined how risk factors like APOE genotype, age, and sex affect inflammatory molecules and AD biomarkers in cerebrospinal fluid (CSF). Among cognitively unimpaired individuals over 65 ( = 298), we measured 365 CSF inflammatory molecules, finding age, sex, and diabetes status predominantly influencing their levels. We observed age-related correlations with AD biomarkers such as total tau, phosphorylated tau-181, neurofilament light chain (NfL), and YKL40. APOE4 was associated with lower Aβ42 and higher SNAP25 in CSF. We explored baseline variables predicting cognitive decline risk, finding age, CSF Aβ42, NfL, and REG4 to be independently correlated. Subjects with older age, lower Aβ42, higher NfL, and higher REG4 at baseline had increased cognitive impairment risk during follow-up. This suggests that assessing CSF inflammatory molecules and AD biomarkers could predict cognitive impairment risk in the elderly.
Healthcare Utilization and Direct Costs Prior to Subspecialty Care in Children with Chronic Pain Compared with Other Chronic Childhood Diseases: A Cohort Study
Gerhold K, Al-Azazi S, El-Matary W, Katz LY, Lim LS, Marks SD and Lix LM
To understand the burden associated with pediatric chronic pain (CP) on the healthcare system compared with other costly chronic diseases prior to subspecialty care.
Cold-induced FOXO1 nuclear transport aids cold survival and tissue storage
Zhang X, Ge L, Jin G, Liu Y, Yu Q, Chen W, Chen L, Dong T, Miyagishima KJ, Shen J, Yang J, Lv G, Xu Y, Yang Q, Ye L, Yi S, Li H, Zhang Q, Chen G, Liu W, Yang Y, Li W and Ou J
Cold-induced injuries severely limit opportunities and outcomes of hypothermic therapies and organ preservation, calling for better understanding of cold adaptation. Here, by surveying cold-altered chromatin accessibility and integrated CUT&Tag/RNA-seq analyses in human stem cells, we reveal forkhead box O1 (FOXO1) as a key transcription factor for autonomous cold adaptation. Accordingly, we find a nonconventional, temperature-sensitive FOXO1 transport mechanism involving the nuclear pore complex protein RANBP2, SUMO-modification of transporter proteins Importin-7 and Exportin-1, and a SUMO-interacting motif on FOXO1. Our conclusions are supported by cold survival experiments with human cell models and zebrafish larvae. Promoting FOXO1 nuclear entry by the Exportin-1 inhibitor KPT-330 enhances cold tolerance in pre-diabetic obese mice, and greatly prolongs the shelf-life of human and mouse pancreatic tissues and islets. Transplantation of mouse islets cold-stored for 14 days reestablishes normoglycemia in diabetic mice. Our findings uncover a regulatory network and potential therapeutic targets to boost spontaneous cold adaptation.
Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990-2021: a systematic analysis for the Global Burden of Disease Study 2021
Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations.
Associations between Sleep Disturbances, Personality Traits and Self-Regulation in a Sample of Healthy Adults
Zakiei A, Sadeghi-Bahmani D, Khazaie H, Lorestani Z, Sadeghi M, Korani D, Sahraei Z, Komasi S, Stanga Z, Brühl AB and Brand S
Scientific evidence and everyday experience show that sleep disturbances and self-regulation as a proxy of stress reactivity are linked. Particular personality traits such as neuroticism, internalizing and externalizing problems are also associated with sleep disturbances. Here, we combined self-regulation and personality traits and associated these variables with subjective sleep disturbances. A total of 846 adults (mean age: 33.7 years; 78.7% females) completed questionnaires covering sleep disturbances, self-regulation and personality traits. Higher scores for sleep disturbances were associated with higher scores for externalization, internalization, and instability and with lower scores for stability (all trait variables) and with poorer self-regulation (state variable). The regression model showed that higher scores for externalization and internalization (traits), and lower scores for self-regulation (state) predicted higher scores for sleep disturbance. Next, self-regulation had both a direct effect on sleep disturbance, and an indirect effect via personality traits. Sleep disturbances were related to both state (i.e., self-regulation) and trait (e.g., internalization and instability) dimensions. The current data analysis leapfrogs the state-trait dichotomy discussion and reconciles the state-and-trait approach in the prediction of poor sleep, though self-regulation appeared to have both direct and indirect effects on sleep disturbances.
Assessing the Clinical Efficacy of a Virtual Reality Tool for the Treatment of Obesity: Randomized Controlled Trial
Anastasiadou D, Herrero P, Garcia-Royo P, Vázquez-De Sebastián J, Slater M, Spanlang B, Álvarez de la Campa E, Ciudin A, Comas M, Ramos-Quiroga JA and Lusilla-Palacios P
Virtual reality (VR) interventions, based on cognitive behavioral therapy principles, have been proven effective as complementary tools in managing obesity and have been associated with promoting healthy behaviors and addressing body image concerns. However, they have not fully addressed certain underlying causes of obesity, such as a lack of motivation to change, low self-efficacy, and the impact of weight stigma interiorization, which often impede treatment adherence and long-term lifestyle habit changes. To tackle these concerns, this study introduces the VR self-counseling paradigm, which incorporates embodiment and body-swapping techniques, along with motivational strategies, to help people living with obesity effectively address some of the root causes of their condition.
Psychosocial Factors and Glycemic Control in Young Adults With Youth-Onset Type 2 Diabetes
Trief PM, Wen H, Burke B, Uschner D, Anderson BJ, Liu X, Bulger J and Weinstock RS
Youth-onset type 2 diabetes is associated with poor glycemic control and early onset of complications. Identification of psychosocial factors associated with poor glycemic control is needed to inform efficacious interventions.
Evaluation of Event-Related Potentials in Somatic Diseases - Systematic Review
Popiołek AK, Niznikiewicz MA, Borkowska A and Bieliński MK
Many somatic illnesses (e.g. hypertension, diabetes, pulmonary and cardiac diseases, hepatitis C, kidney and heart failure, HIV infection, Sjogren's disease) may impact central nervous system functions resulting in emotional, sensory, cognitive or even personality impairments. Event-related potential (ERP) methodology allows for monitoring neurocognitive processes and thus can provide a valuable window into these cognitive processes that are influenced, or brought about, by somatic disorders. The current review aims to present published studies on the relationships between somatic illness and brain function as assessed with ERP methodology, with the goal to discuss where this field of study is right now and suggest future directions.
Relative associations of behavioral and physiological risks for cardiometabolic disease with cognition in bipolar disorder during mid and later-life: findings from the UK biobank
Ringin E, Dunstan DW, Meyer D, McIntyre RS, Owen N, Berk M, Hallgren M, Rossell SL and Van Rheenen TE
Cardiometabolic disease risk factors are disproportionately prevalent in bipolar disorder (BD) and are associated with cognitive impairment. It is, however, unknown which health risk factors for cardiometabolic disease are relevant to cognition in BD. This study aimed to identify the cardiometabolic disease risk factors that are the most important correlates of cognitive impairment in BD; and to examine whether the nature of the relationships vary between mid and later life.
Artificial night light and thyroid cancer
Tselebis A, Koukkou E, Milionis C, Zabuliene L, Pachi A and Ilias I
The occurrence of thyroid cancer (TC) has increased in recent decades. Exposure to outdoor artificial light at night (ALN) is associated with an increased risk of cancer.
Eating habits and sleep quality in individuals with type 1 diabetes on continuous glucose monitoring and insulin pump
Corrado A, Scidà G, Vitale M, Caprio B, Costabile G, Annuzzi E, Della Pepa G, Lupoli R and Bozzetto L
Sleep disorders are bidirectionally linked with eating behaviors and glucose metabolism, which could be clinically relevant in type 1 diabetes (T1D). We investigated the relationship between dietary habits and sleep quality in individuals with T1D on insulin pumps and continuous glucose monitoring (CGM).
Severe Early-Onset Obesity and Diabetic Ketoacidosis due to a Novel Homozygous c.169C>T p.Arg57* Variant in Gene
Cayir A, Turkyilmaz A, Rabenstein H, Guven F, Karagoz YS, Vuralli D, Wabitsch M and Demirbilek H
Early-onset severe obesity is usually the result of an underlying genetic disorder, and several genes have recently been shown to cause syndromic and nonsyndromic forms of obesity. The " () gene encodes for a centrosomal and ciliary protein. Homozygous variants in the gene are extremely rare causes of early-onset severe monogenic obesity. Herein, we present a Turkish family with early-onset severe obesity with variable features.
Clinical Accuracy of Serum Neurofilament Light to Differentiate Frontotemporal Dementia from Primary Psychiatric Disorders is Age-Dependent
Light V, Jones SL, Rahme E, Rousseau K, de Boer S, Vermunt L, Soltaninejad M, Teunissen C, Pijnenburg Y, Ducharme S and Consortium FS
Symptoms of behavioral variant frontotemporal dementia (bvFTD) overlap with primary psychiatric disorders (PPD) making diagnosis challenging. Serum neurofilament light (sNfL) is a candidate biomarker to distinguish bvFTD from PPD, but large-scale studies in PPD are lacking.
Primary Care Clinic Approaches to Facilitating Patient Health Behavior Change in Alabama
Distler KR, Lindsey MJ, Mims MH, Taylor MA and Hollingsworth JC
Background  Non-communicable chronic diseases (NCCDs), such as cardiovascular disease, diabetes, and cancer, are the leading cause of death and disability and the leading driver of healthcare costs in the U.S. It is estimated that 80% of chronic diseases and premature deaths are attributable to modifiable lifestyle factors related to smoking and alcohol intake, poor eating patterns, and physical inactivity. Inadequate sleep also plays a significant role. Among other directives, primary care providers (PCPs) have the opportunity to contribute to preventing and treating NCCD in their patients. Comprehensive, evidence-based behavioral counseling interventions are recommended to PCPs as a first-line approach to improving outcomes. However, presumably due to a lack of PCP time, training or resources, most patients report not receiving such services. Currently, the extent to which PCPs in Alabama offer or refer patients to health behavior change (HBC) services is unknown.  Objectives  This study aims to assess the following: (1) Alabama PCPs' current approaches in facilitating patient HBC in the domains of eating patterns, physical activity, sleep, and stress and (2) the likelihood of the Alabama PCPs referring patients to virtual HBC programs, once developed by an osteopathic medical school in the state.  Methods  Data were collected from clinic personnel who were knowledgeable regarding the clinic's approach to facilitating patient HBC via scripted telephone interviews and online surveys sent via email. The clinic list utilized for the study was derived from a list of VCOM-Auburn clinical preceptors. Primary care and specialty clinics were included. Data were analyzed descriptively to determine the number of clinics that (1) provide, recommend, or refer programs, services, or resources to patients to facilitate HBC related to eating patterns, physical activity, sleep, and stress management and (2) are likely to refer patients to free virtual HBC programs, once developed by an osteopathic medical school in the state. Results  Of the 198 clinics that were contacted, 75 were excluded, 46 were "no response," 53 agreed to participate, and 50 completed the survey. Of the 50 clinics that completed the survey, 33 indicated offering resources or referrals for diet, 29 stated they offered resources or referral services for physical activity, 33 indicated offering resources or referrals for sleep, and 28 indicated offering or recommending resources for stress management to patients. Most of the clinics (29/50) felt that their patients would benefit most from a program that facilitates improvement in eating patterns, and 41/50 clinics said that they are either "somewhat" or "extremely" likely to refer patients to a free VCOM-Auburn HBC program, once available.  Conclusions Findings indicate that a significant percentage of PCP clinics are not offering HBC resources to patients and that most PCP clinics would consider referring patients to free VCOM-Auburn HBC programs, once available. Phone data were significantly different from email data. The primary limitations were a low response rate and potential response bias.
KAT7/HMGN1 signaling epigenetically induces tyrosine phosphorylation-regulated kinase 1A expression to ameliorate insulin resistance in Alzheimer's disease
Lu QS, Ma L, Jiang WJ, Wang XB and Lu M
Epidemiological studies have revealed a correlation between Alzheimer's disease (AD) and type 2 diabetes mellitus (T2D). Insulin resistance in the brain is a common feature in patients with T2D and AD. KAT7 is a histone acetyltransferase that participates in the modulation of various genes.
Inflammatory Dietary Potential Is Associated with Vitamin Depletion and Gut Microbial Dysbiosis in Early Pregnancy
Alvernaz SA, Wenzel ES, Nagelli U, Pezley LB, LaBomascus B, Gilbert JA, Maki PM, Tussing-Humphreys L and Peñalver Bernabé B
Pregnancy alters many physiological systems, including the maternal gut microbiota. Diet is a key regulator of this system and can alter the host immune system to promote inflammation. Multiple perinatal disorders have been associated with inflammation, maternal metabolic alterations, and gut microbial dysbiosis, including gestational diabetes mellitus, pre-eclampsia, preterm birth, and mood disorders. However, the effects of high-inflammatory diets on the gut microbiota during pregnancy have yet to be fully explored. We aimed to address this gap using a system-based approach to characterize associations among dietary inflammatory potential, a measure of diet quality, and the gut microbiome during pregnancy. Forty-seven pregnant persons were recruited prior to 16 weeks of gestation. Participants completed a food frequency questionnaire (FFQ) and provided fecal samples. Dietary inflammatory potential was assessed using the Dietary Inflammatory Index (DII) from the FFQ data. Fecal samples were analyzed using 16S rRNA amplicon sequencing. Differential taxon abundances with respect to the DII score were identified, and the microbial metabolic potential was predicted using PICRUSt2. Inflammatory diets were associated with decreased vitamin and mineral intake and a dysbiotic gut microbiota structure and predicted metabolism. Gut microbial compositional differences revealed a decrease in short-chain fatty acid producers such as , and an increase in predicted vitamin B12 synthesis, methylglyoxal detoxification, galactose metabolism, and multidrug efflux systems in pregnant individuals with increased DII scores. Dietary inflammatory potential was associated with a reduction in the consumption of vitamins and minerals and predicted gut microbiota metabolic dysregulation.
Prevalence, Morbidity, and Mortality of Men With Sex Chromosome Aneuploidy in the Million Veteran Program Cohort
Davis SM, Teerlink C, Lynch JA, Gorman BR, Pagadala M, Liu A, Panizzon MS, Merritt VC, Genovese G, Ross JL and Hauger RL
The reported phenotypes of men with 47,XXY and 47,XYY syndromes include tall stature, multisystem comorbidities, and poor health-related quality of life (HRQOL). However, knowledge about these sex chromosome aneuploidy (SCA) conditions has been derived from studies in the less than 15% of patients who are clinically diagnosed and also lack diversity in age and genetic ancestry.
GAUSS: a summary-statistics-based R package for accurate estimation of linkage disequilibrium for variants, Gaussian imputation, and TWAS analysis of cosmopolitan cohorts
Lee D and Bacanu SA
As the availability of larger and more ethnically diverse reference panels grows, there is an increase in demand for ancestry-informed imputation of genome-wide association studies (GWAS), and other downstream analyses, e.g. fine-mapping. Performing such analyses at the genotype level is computationally challenging and necessitates, at best, a laborious process to access individual-level genotype and phenotype data. Summary-statistics-based tools, not requiring individual-level data, provide an efficient alternative that streamlines computational requirements and promotes open science by simplifying the re-analysis and downstream analysis of existing GWAS summary data. However, existing tools perform only disparate parts of needed analysis, have only command-line interfaces, and are difficult to extend/link by applied researchers.
Relationship between functional connectivity and weight-gain risk of antipsychotics in schizophrenia
Dodd K, Legget KT, Cornier MA, Novick AM, McHugo M, Berman BD, Lawful BP and Tregellas JR
The mechanisms by which antipsychotic medications (APs) contribute to obesity in schizophrenia are not well understood. Because AP effects on functional brain connectivity may contribute to weight effects, the current study investigated how AP-associated weight-gain risk relates to functional connectivity in schizophrenia.
State-dependent central synaptic regulation by GLP-1 is essential for energy homeostasis
Wang L, Savani R, Bernabucci M, Lu Y, Singh I, Xu W, El Ouaamari A, Wheeler MB, Grill HJ, Rossi MA and Pang ZP
Central nervous system (CNS) control of metabolism plays a pivotal role in maintaining energy homeostasis. Glucagon-like peptide-1 (GLP-1, encoded by ), secreted by a distinct population of neurons located within the nucleus tractus solitarius (NTS), suppresses feeding through projections to multiple brain targets. Although GLP-1 analogs are proven clinically effective in treating type 2 diabetes and obesity, the mechanisms of GLP-1 action within the brain remain unclear. Here, we investigate the involvement of GLP-1 receptor (GLP-1R) mediated signaling in a descending circuit formed by GLP-1R neurons in the paraventricular hypothalamic nucleus (PVN) that project to dorsal vagal complex (DVC) neurons of the brain stem in mice. PVN→DVC synapses release glutamate that is augmented by GLP-1 via a presynaptic mechanism. Chemogenetic activation of PVN→DVC neurons suppresses feeding. The PVN→DVC synaptic transmission is dynamically regulated by energy states. In a state of energy deficit, synaptic strength is weaker but is more profoundly augmented by GLP-1R signaling compared to an energy-replete state. In an obese state, the dynamic synaptic strength changes in the PVN→DVC descending circuit are disrupted. Blocking PVN→DVC synaptic release or ablation of GLP-1R in the presynaptic compartment increases food intake and causes obesity, elevated blood glucose, and impaired insulin sensitivity. These findings suggest that the state-dependent synaptic plasticity in this PVN→DVC descending circuit mediated by GLP-1R signaling is an essential regulator of energy homeostasis.
Comprehensive transition of care for polycystic ovary syndrome from adolescence to adulthood
Simon SL, Phimphasone-Brady P, McKenney KM, Gulley LD, Bonny AE, Moore JM, Torres-Zegarra C and Cree MG
Polycystic ovary syndrome (PCOS) is a lifelong chronic condition that affects one in ten females and can be diagnosed in adolescence. As adolescents with PCOS transition to adulthood, counselling for lifestyle management and mental health concerns often transition from involving the family unit to increasingly individual-focused approaches. PCOS is associated with a large range of comorbidities affecting reproductive, metabolic, dermatological, and psychological health. The diagnosis and comorbidities of PCOS are influenced by pubertal hormones and need to be reassessed continuously to ensure that treatment remains appropriate for age and development. As young patients grow up, personal concerns often change, especially in relation to reproductive management. In this Review, we present prevalence rates, screening tools, and treatment recommendations for PCOS-related conditions, and we consider the diagnostic and clinical elements of optimal transition of care models that ensure continuity of comprehensive care for adolescents moving from the paediatric health-care system to the adult health-care system.
Risk factors associated with cognitive performance and cognitive impairment in older adults with type 1 diabetes: Data from the Wireless Innovation for Seniors with Diabetes Mellitus (WISDM) study
Fonseca LM, Kanapka L, Miller K, Pratley R, Rickels MR, Rizvi S, Kudva YC, Weinstock RS and Chaytor NS
Adults with type 1 diabetes (T1D) are considered at increased risk for cognitive impairment and accelerated brain aging. However, longitudinal data on cognitive impairment and dementia in this population are scarce.
The Role of Metacognition in the Prediction of Depressive and Anxiety Symptoms in Chronically Ill Patients
Kołodziejczyk A, Krawczyk J, Tkaczyszyn-Mika E, Gniewczyńska J, Ziarko M, Zozulińska-Ziółkiewicz D and Pawłowski T
Cancer, diabetes, and heart diseases are frequent causes of depression and anxiety. The study explored the metacognitive beliefs manifested by chronically ill patients and the presence of depressive or anxiety symptoms and the predictive role of metacognition in both.
Traumatic stress symptoms, mental splitting and burnout in health care professionals: a cross-sectional study
Riethof N and Bob P
Burnout syndrome usually begins with feelings of enthusiasm and idealized visualizations, and it is in contrast with subsequent disillusionment, disappointment, and symptoms which are related to chronic stress experienced later. This tendency to idealization is a parallel to the concept of "mental splitting" described by Kernberg with a pronounced "black and white" perceptual dichotomy between the early idealization and later disillusionment. This study intends examination of relationships between burnout syndrome, traumatic stress and Kernberg's concept of splitting.
Assessing cognitive impairment in home-dwelling Chinese elders aged 80+: a detailed survey of 13,000 participants focusing on demographic factors, social engagement, and disease prevalence
Bian S, Tian X, Meng F, Xu C, Zhao Y, Gao Q and Bian C
Cognitive Impairment (CI) in the elderly, encompassing conditions ranging from Mild Cognitive Impairment (MCI) to dementia, represents a growing public health concern globally. This study aims to investigate the prevalence and correlates of CI among individuals aged 80 and above.
A Systematic Guideline by the ASPN Workgroup on the Evidence, Education, and Treatment Algorithm for Painful Diabetic Neuropathy: SWEET
Sayed D, Deer TR, Hagedorn JM, Sayed A, D'Souza RS, Lam CM, Khatri N, Hussaini Z, Pritzlaff SG, Abdullah NM, Tieppo Francio V, Falowski SM, Ibrahim YM, Malinowski MN, Budwany RR, Strand NH, Sochacki KM, Shah A, Dunn TM, Nasseri M, Lee DW, Kapural L, Bedder MD, Petersen EA, Amirdelfan K, Schatman ME and Grider JS
Painful diabetic neuropathy (PDN) is a leading cause of pain and disability globally with a lack of consensus on the appropriate treatment of those suffering from this condition. Recent advancements in both pharmacotherapy and interventional approaches have broadened the treatment options for PDN. There exists a need for a comprehensive guideline for the safe and effective treatment of patients suffering from PDN.
Spatial characteristics of non-communicable diseases and their associations to social conditions in a large urban cohort in Germany-Results from the Hamburg City Health Study
Andrees V, Bei der Kellen R, Augustin M, Gallinat J, Harth V, Hoven H, Kühn S, Lautenbach A, Magnussen C, Mohr N, Twerenbold R, Schäfer I, Waschki B, Zyriax BC and Augustin J
Non-communicable diseases (NCDs) are responsible for many deaths. They are associated with several modifiable and metabolic risk factors and are therefore prone to significant regional variations on different scales. However, only few intra-urban studies examined spatial variation in NCDs and its association with social circumstances, especially in Germany. Thus, the present study aimed to identify associations of personal risk factors and local social conditions with NCDs in a large German city.
Prevalence and predictors of diabetes distress and depression in people with type 1 diabetes
AlOzairi A, Irshad M, AlKandari J, AlSaraf H and Al-Ozairi E
People living with diabetes often encounter psychosocial challenges, including diabetes distress and depression. Despite this, little research has focused on the co-occurrence of these conditions. This study aimed to explore the prevalence of depressive symptoms and diabetes distress in people with type 1 diabetes in Kuwait and to identify clinical and demographic factors associated with these conditions.
Impact of the geriatric nutritional risk index on long-term outcomes in patients undergoing hemodialysis: a meta-analysis of observational studies
Hung KC, Kao CL, Hsu CW, Yu CH, Lin CM, Chen HT, Chang YJ, Liao SW and Chen IW
This meta-analysis aimed to synthesize current evidence on the association between the Geriatric Nutritional Risk Index (GNRI) and long-term outcomes in patients undergoing hemodialysis.
Association between physical multimorbidity and common mental health disorders in rural and urban Malawian settings: Preliminary findings from Healthy Lives Malawi long-term conditions survey
Nkoka O, Munthali-Mkandawire S, Mwandira K, Nindi P, Dube A, Nyanjagha I, Mainjeni A, Malava J, Amoah AS, McLean E, Stewart RC, Crampin AC and Price AJ
In low-income Africa, the epidemiology of physical multimorbidity and associated mental health conditions is not well described. We investigated the multimorbidity burden, disease combinations, and relationship between physical multimorbidity and common mental health disorders in rural and urban Malawi using early data from 9,849 adults recruited to an on-going large cross-sectional study on long-term conditions, initiated in 2021. Multimorbidity was defined as having two or more measured (diabetes, hypertension) or self-reported (diabetes, hypertension, disability, chronic pain, HIV, asthma, stroke, heart disease, and epilepsy) conditions. Depression and anxiety symptoms were measured using the 9-item Patient Health Questionnaire (PHQ-9) and the 7-item General Anxiety Disorder scale (GAD-7) and defined by the total score (range 0-27 and 0-21, respectively). We determined age-standardized multimorbidity prevalence and condition combinations. Additionally, we used multiple linear regression models to examine the association between physical multimorbidity and depression and anxiety symptom scores. Of participants, 81% were rural dwelling, 56% were female, and the median age was 30 years (Inter Quartile Range 21-43). The age-standardized urban and rural prevalence of multimorbidity was 14.1% (95% CI, 12.5-15.8%) and 12.2% (95% CI, 11.6-12.9%), respectively. In adults with two conditions, hypertension, and disability co-occurred most frequently (18%), and in those with three conditions, hypertension, disability, and chronic pain were the most common combination (23%). Compared to adults without physical conditions, having one (B-Coefficient (B) 0.79; 95% C1 0.63-0.94%), two- (B 1.36; 95% CI 1.14-1.58%), and three- or more- physical conditions (B 2.23; 95% CI 1.86-2.59%) were associated with increasing depression score, p-trend <0.001. A comparable 'dose-response' relationship was observed between physical multimorbidity and anxiety symptom scores. While the direction of observed associations cannot be determined with these cross-sectional data, our findings highlight the burden of multimorbidity and the need to integrate mental and physical health service delivery in Malawi.
Correlation between maternal and umbilical cord 25-hydroxy-vitamin D levels over a range of values. A prospective observational study from the United Arab Emirates
Jutell M, Bhat S, Bagge ML, Isberg PE and Wiberg N
Worldwide vitamin D insufficiency is remarkably prevalent in both children and adults, including pregnant women. The total amount of the vitamin is best measured by 25-hydroxy-vitamin D (25(OH)D), which is a measurement of total serum cholecalciferol 25(OH)D3 and ergocalciferol 25(OH)D2. There is a known correlation between maternal and umbilical cord blood (UCB) 25(OH)D; however, whether specific maternal demographics or comorbidities influence the correlation remains uncertain. This prospective observational study was designed to study if maternal 25(OH)D levels, maternal age and BMI, amount of supplementation, mode of delivery, diabetes, hypertension/preeclampsia, or sunlight exposure had an impact on the correlation. Women were enrolled in the study at admission to the labor ward. If they agreed to participate, venous blood was directly collected and analyzed for 25(OH)D. The UCB was sampled after delivery from the unclamped cord and immediately analyzed for 25(OH)D. ANOVA, Fisher's exact test, Pearson's correlation, and test of the differences between correlations using Fisher's z-transformation with Bonferroni correction were used accordingly. Of the 298 women enrolled, blood from both the mother and umbilical cord was analyzed successfully for 25(OH)D in 235 cases. The crude correlation between maternal and UCB 25(OH)D was very strong over all values of 25(OH)D (r = 0.905, R2 = 0.821, p <0,001) and remained strong independently of maternal demographics or co-morbidities (r ≥ 0.803, R2 ≥ 0.644, p <0.001). For women who delivered by caesarean section in second stage the correlation was strong (r ≥ 0.633, R2 ≥ 0.4, p <0.037). Test of differences between correlations showed significant stronger correlation in women with unknown 25(OH)D3 supplementation compared to women receiving 10.000 IU/week (p = 0.02) and 20.000IU/week (p = 0.01) and that the correlation was significantly stronger for women with a BMI of 25-29.9 compared to women with a BMI of <24.9 (p = 0.004) and 30-34.9 (p = 0.002). 213 (91%) women had lower 25(OH)D compared to the neonate, with a mean difference of -13.7nmol/L (SD = 15.6). In summary, the correlation between maternal and UCB 25(OH)D is very strong throughout low to high maternal levels of 25(OH)D with lower levels in maternal blood. Typical maternal demographics and comorbidities did not affect the transition.
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