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Temporal patterns of food consumption and their association with cardiovascular risk in rotating shift workers
Selingardi SA, Ribeiro SMLT, Freitas SN, Pimenta FAP, Machado-Coelho GLL, Oliveira FLP, Neto RMDN and Menezes-Júnior LAA
We aimed to evaluate the association of temporal patterns of food consumption with cardiovascular disease (CVD) risk.
Implementation of nutritional screening tools, nutritional assessment tools, and diagnostic criteria for malnutrition in convalescent rehabilitation wards: A nationwide survey
Nishioka S, Takayama M, Okamoto T and Miyai I
The utilization of recommended nutritional assessment measures in rehabilitation settings remains unclear. This study explored methods for identifying nutritional disorders using data from a nationwide survey conducted in convalescent rehabilitation wards.
Standardising and simplifying the Global Leadership Initiative on Malnutrition (GLIM) for its more general application
Kurik G, Kelly-Bissue C, Lõhmus A, Muhhamedjanov K, Ilves N and Forbes A
Malnutrition is present in 20-50% of hospital patients but its recognition is often neither timely nor complete. The Global Leadership Initiative on Malnutrition (GLIM) aims to improve this, but its successful implementation may be compromised by its dependence on (a choice of) prior screening tools and difficulties in consistent assessment of muscle mass.
Nutrition-related predictors of complications and length of hospital stay following total pelvic exenteration surgery
Watt A, Kaushik V, Harris C, Yeung CH, Lam YN and Osland E
Pelvic exenteration (PE) surgery is now a widely accepted procedure that is increasingly being performed worldwide but has significant morbidity. Although nutrition status, body mass index (BMI) and postoperative nutrition support practices are modifiable risk factors, few studies have examined the relationship of these with clinical outcomes following PE. The aim of this study was therefore to investigate the impact of these factors on postoperative complications and length of hospital stay (LOHS) following PE.
Reduced trunk muscle mass in patients with stroke is associated with reduced balance function recovery
Sato K and Ogawa T
Skeletal muscles are essential for postural retention and balance function. However, the relationship between trunk muscle mass (TMM) and balance function has not yet been clarified. This study aimed to examine the impact of TMM on the change in balance function in patients with stroke from admission to a rehabilitation hospital to discharge.
Human milk proteins differentiate over the sex of newborns and across stages of lactation
Bernardes-Loch RM, Ribeiro AC, Ramírez-López CJ, Loch Gomes RA, Barros E, Filomeno Fontes EA and Baracat-Pereira MC
Human milk (HM) is a complete food that meets the nutritional and energy demands of the newborns. It contains numerous bioactive components, including functional proteins. Variations in HM energy and lipid content have already been reported related to the newborn's sex, but differences between protein profiles are still scarce. This work aimed to identify differences between HM proteins produced by mothers of female and male newborns, in the lactation stages of colostrum and mature milk, and the metabolic pathways involved.
The association between the 'at risk of developing undernutrition' category of the Short Nutritional Assessment Questionnaire 65+ and incident undernutrition in community-dwelling older adults
van Beek SW, Wijnhoven HA and Visser M
Screening tools like the Short Nutritional Assessment Questionnaire 65+ (SNAQ) have been developed for the early recognition of undernutrition in older adults. The SNAQ screens for being undernourished (red), being 'at risk of developing undernutrition' (i.e. 'at risk', orange), or 'not at risk' (green). This study investigated whether community-dwelling older adults 'at risk' (orange) are more likely to develop undernutrition during a 3-year follow-up compared to those 'not at risk' (green).
Inflammation, but not skeletal muscle index, is associated with coronavirus disease 2019 mortality in patients with cancer
Souza NC, Saraiva DDCA, Murad LB, Murad LD, do Amaral Paes TC, Feijó PM, Rodrigues VD, de Pinho NB, Barreto AB, Tostes NF, Couto ADS and Martucci RB
Patients with cancer and coronavirus disease 2019 (COVID-19) have characteristics that can cause the most severe forms of the disease and higher mortality. We aimed to assess the association between computed tomography (CT)-derived muscle abnormalities, anthropometric parameters, inflammation, and mortality in patients with cancer and COVID-19.
A leaky gut contributes to postural imbalance in male patients with chronic obstructive pulmonary disease
Qaisar R, Hussain S, Karim A, Muhammad T, Ustrana S, Azhar Hussain M and Ahmad F
Patients with chronic obstructive pulmonary disease (COPD) frequently exhibit an inability to maintain postural balance. However, the contribution of increased intestinal permeability or leaky gut to the postural imbalance in COPD is not known.
Family caregivers' better nutritional status is associated with care recipients' better nutritional status
Koponen S, Nykänen I, Savela RM, Välimäki T, Suominen AL and Schwab U
A high proportion of older care recipients (CRs) face malnutrition and risk of malnutrition, affecting their functional abilities and posing challenges for caregiving. The aim of this study was to assess the risk for malnutrition among older CRs and the associated characteristics of both CRs and family caregivers (FCs) with nutritional status of CRs.
Prognostic value of body composition in patients with digestive tract cancers: A prospective cohort study of 8,267 adults from China
Han J, Liu X, Wang J, Tang M, Xu J, Tan S, Liu X and Wu G
The characterization and prognostic value of body composition parameter/phenotype based on computed tomography (CT) in patients with digestive tract cancers remain incomplete. This study aimed to investigate the relationship between parameter/phenotype and clinical outcomes in patients with digestive tract cancers.
Association of the muscle mass phenotype as assessed by a grading system with the quality of life of patients with incurable cancer in palliative care
Wiegert EVM, Oliveira LC, Rosa KSDC and Calixto-Lima L
Loss of muscle mass (MM) is common in advanced stages of cancer, with an impact on worsening quality of life (QoL). In the current study the relationship of a previously proposed simple grade system to assess MM phenotypes with QoL was investigated to strengthen its clinical significance.
Pulmonary rehabilitation: A cohort study assessing the effectiveness of a multi-professional nutrition intervention
Holst M, Geisler L, Mikkelsen S, Rasmussen HH, Jørgensen BG and Beck AM
Limited benefit of pulmonary exercise rehabilitation has been associated with fulfilment of energy and protein requirements.
Plasma metabolomics changes comparing daytime to overnight infusions of home parenteral nutrition in adult patients with short bowel syndrome: Secondary analysis of a clinical trial
Dashti HS, Sevilla-Gonzalez M, Mogensen KM, Winkler MF and Compher C
Home parenteral nutrition (HPN) is often cycled nocturnally and is expected to result in glucose intolerance and sleep disruption partly due to circadian misalignment. This study aimed to define the metabolic response when HPN is cycled during the daytime compared to overnight.
Association of serum vitamin D and the risk of cardiovascular diseases among diabetic patients: A systematic review and meta-analysis
Iqhrammullah M, Gusti N, Andika FF and Abdullah A
The emerging role of vitamin D has drawn the attention of researchers around the world, including its involvement in cardiovascular complications among individuals with diabetes.
Evaluation of the effectiveness of curcumin and piperine co-supplementation on inflammatory factors, cardiac biomarkers, atrial fibrillation, and clinical outcomes after coronary artery bypass graft surgery
Tehrani SD, Hosseini A, Shahzamani M, Heidari Z, Askari G, Majeed M, Sahebkar A and Bagherniya M
Coronary artery bypass graft (CABG) is one of the preferred treatments for patients with heart problems, especially in individuals with other comorbidities and when multiple arteries are narrowed. This study aimed to assess the effects of administrating curcumin-piperine on patients who underwent CABG surgery.
Habitual coffee and tea consumption and risk of cataract: A prospective cohort study from the UK Biobank
Qi J, Zhang K, Zhang P, Chen C, Zhao C, Lu Y and Zhu X
To study the association of habitual coffee and tea consumption with the risk of cataract.
Effect of calcium supplementation on reversing metformin-based inhibition of vitamin B bioavailability in healthy adults using a [C] cyanocobalamin tracer - A pilot study
Muralidharan J, Romould GG, Kashyap S, Pasanna R, Sivadas A, Sachdev HS, Kurpad AV and Devi S
Metformin is a widely prescribed first line drug for the treatment of type 2 diabetes mellitus (DM). Studies have shown that the use of metformin is often associated with a decrease in vitamin B (B) levels in patients with DM. Few studies have shown that this effect could be mitigated with calcium supplementation. In the present study, we quantified the effect of metformin, and metformin co-administered with calcium on B absorption using a novel stable isotope [C] cyanocobalamin tracer.
Malnutrition and cachexia are associated with poor CAR T-cell therapy outcomes including survival
Cucchiaro B, Davies NA, Weekes CE, O'Reilly M, Roddie C and Slee A
Chimeric Antigen Receptor (CAR) T-cell therapy has emerged as a revolutionary treatment for patients with refractory or relapsed B-cell malignancies. However, a significant proportion of patients experience negative outcomes, including severe inflammatory toxicities and relapse. Cachexia and malnutrition are known secondary syndromes in many cancer patients, attributed to the effects of active malignancy, systemic inflammation, and cumulative treatment burden; however, further research is required to accurately characterise these issues in CAR T-cell patients. The aims of this service evaluation were to explore the changes in nutritional status (malnutrition and cachexia) in CAR T-cell therapy patients and the potential impact on patient outcomes including survival. Additionally, we describe the utilisation of dietetic resources in this specific patient population in a London tertiary referral centre.
Maternal gluten, cereal, and dietary fiber intake during pregnancy and lactation and the risk of islet autoimmunity and type 1 diabetes in the child
Hakola L, Lund-Blix NA, Takkinen HM, Tapanainen H, Niinistö S, Korhonen TE, Stene LC, Hyöty H, Toppari J, Ilonen J, Knip M, Veijola R, Virtanen SM and
Maternal gluten intake in relation to child's risk of type 1 diabetes has been studied in few prospective studies considering the diet during pregnancy but none during lactation. Our aim was to study whether gluten, cereals, or dietary fiber in maternal diet during pregnancy and lactation is associated with the risk of islet autoimmunity or type 1 diabetes in the offspring.
An integrated diabetes and mental health intervention for people with type 1 diabetes and severe disordered eating: a prospective proof-of-concept cohort study
Ismail K, Turner D, Brown J, Rosenthal M, Ayis S, Oliver N, Liu YF, Harrison A, Garrett C, Hopkins D, Treasure J, Valabhji J, Thomas S and Stadler M
[Epidemiological characteristics of spontaneous subarachnoid hemorrhage cases in Shandong province]
Zhang BY, Zhang JY, Chu J, Lu ZL, Xu XH, Yu XH, Guo XL, Xu AQ and Ma JX
To investigate the characteristics and trends of spontaneous subarachnoid hemorrhage (SAH) in Shandong province. In this study, SAH incidence data of residents from 2012 to 2021 were collected from the chronic disease monitoring information management system of Shandong province, including the basic information of outpatient, emergency or inpatient cases and out-of-hospital deaths (name, gender, ID number, address, etc.) and disease diagnosis information (disease diagnosis, date of onset, date of diagnosis, etc.). The crude incidence rate and age-standardized incidence rate were used as indicators to describe the incidence of SAH in different gender, age groups and regions (urban and rural areas). Joinpoint regression was used to analyze the variation of incidence rate and age by year. The rate difference decomposition method was used to estimate the contribution of population aging to the increase of SAH incidence. Global and local spatial autocorrelation analysis was performed using DeoDa 1.12 software. From 2012 to 2021, a total of 11 629 cases of SAH were reported from 19 provincial monitoring sites in Shandong province. Among them, 54.11% (6 293 cases) were female and 91.87% (10 684 cases) were≥45 years old. The reported crude incidence rate increased from 5.26/100 000 to 9.50/100 000, with an average annual increase of 7.75% (=7.30, <0.001), and the standardized incidence rate also showed an upward trend (=3.92, =0.004). The crude incidence rate of women was higher than that of men in all years (all values<0.05), and the standardized incidence rate of women was higher than that of men in all years except in 2012 and 2021 (all values<0.05). In 2012, the crude incidence and standardized incidence of urban residents were lower than those in rural areas (<0.05); from 2013 to 2017, the urban incidence was higher than that in rural areas; and after 2018, the rural incidence exceeded the urban incidence again (all values<0.05). The median age of onset of SAH increased from 61.9 years in 2012 to 67.2 years in 2021. The age of onset of SAH in men was lower than that in women in all years (all <0.05), and there was no significant difference between urban and rural residents in most years (>0.05). The incidence of SAH increased with age (<0.001), with a low incidence reported in residents aged<45 years and a rapid increase in residents aged≥45 years. According to the seasonal decomposition, the incidence of SAH had three small peaks in January, March to May and October to November. From 2013 to 2021, the contribution of aging population to the increase of crude incidence of SAH increased from 27.86% to 43.68%. The global spatial autocorrelation analysis showed that the incidence of SAH was in an obvious spatial aggregation distribution (Moran's >0, <0.05). Local spatial autocorrelation analysis showed that the counties with high incidence were mainly concentrated in Dezhou City in northwest Shandong Province and Heze city in southwest Shandong province. The crude incidence rate of SAH in Shandong province is increasing, with spatial clustering and seasonal clustering. Residents aged 45 years and older, female residents, and rural residents are at high risk of developing SAH, so targeted prevention and control measures should be taken for high-incidence seasons, high-risk groups, and high-incidence clustered areas.
First-Strike Rapid Predictive Dosimetry and Dose Response for Lu-PSMA Therapy in Metastatic Castration-Resistant Prostate Cancer
Kao YH, Falzone N, Pearson M and Sivaratnam D
We devised and clinically validated a schema of rapid personalized predictive dosimetry for Lu-PSMA-I&T in metastatic castration-resistant prostate cancer. It supersedes traditional empiric prescription by providing clinically meaningful predicted absorbed doses for first-strike optimization. Prostate-specific membrane antigen PET was conceptualized as a simulation study that captures the complex dosimetric interplay between tumor, marrow, and kidneys at a single time point. Radiation principles of fractionation, heterogeneity, normal-organ constraints (marrow, kidney), absorbed dose, and dose rate were introduced. We created a predictive calculator in the form of a free, open-source, and user-friendly spreadsheet that can be completed within minutes. Our schema achieves speed and accuracy by sampling tissue radioconcentrations (kBq/cm) to be analyzed in conjunction with clinical input from the user that reflect dosimetric preconditions. The marrow-absorbed dose constraint was 0.217 Gy (dose rate, ≤0.0147 Gy/h) per fraction with an interfraction interval of at least 6 wk. Our first 10 patients were analyzed. The first-strike mean tumor-absorbed dose threshold for any prostate-specific antigen (PSA) response was more than 10 Gy (dose rate, >0.1 Gy/h). The metastasis with the lowest first-strike tumor-absorbed dose correlated the best with the percentage decrease of PSA; its threshold to achieve hypothetical zero PSA was 20 Gy or more. Each patient's PSA doubling time can be used to personalize their unique absorbed dose-response threshold. The predicted mean first-strike prescription constrained by marrow-absorbed dose rate per fraction was 11.0 ± 4.0 GBq. Highly favorable conditions (tumor sink effect) were dosimetrically expressed as the combination of tumor-to-normal-organ ratios of more than 150 for marrow and more than 4 for kidney. Our schema obviates the traditional role of the SUV as a predictive parameter. Our rapid schema is feasible to implement in any busy real-world theranostics unit and exceeds today's best practice standards. Our dosimetric thresholds and predictive parameters can radiobiologically rationalize each patient's first-strike prescription down to a single becquerel. Favorable tumor-to-normal-organ ratios can be prospectively exploited by predictive dosimetry to optimize the first-strike prescription. The scientific framework of our schema may be applied to other systemic radionuclide therapies.
[Risk factors for progression to chronic kidney disease in patients with cardiac valve replacement surgery-associated acute kidney injury]
Fan XG, You ZZ, Wang S, Huo S, Zhu MY, Yan L, Gu Y and Shao FM
To explore the risk factors for progression to chronic kidney disease (CKD) in patients with cardiac valve replacement surgery-associated acute kidney injury (AKI). A retrospective, nested case-control study was conducted at Fuwai Central China Cardiovascular Hospital. The study subjects were patients who underwent cardiac valve replacement surgery from January 1, 2018 to December 31, 2020, with a baseline estimated glomerular filtration rate (eGFR)>60 ml·min·(1.73 m) and postoperative complication of AKI. The patients were followed up for 90 days after discharge from hospital. The endpoint event was defined as progression to CKD 90 days after the occurrence of cardiac valve replacement surgery-associated AKI. The patients were divided into CKD group and non-CKD group based on whether they experienced endpoint event. The baseline clinical data were compared between the two groups. The measurement data with non-normal distribution was represented as (,). Logistic regression model was used to analyze the risk factors of endpoint event. The receiver-operating characteristic (ROC) curve was drawn to evaluate the performance for predicting CKD in cardiac valve replacement surgery-associated AKI patients. A total of 149 cardiac valve replacement surgery-associated AKI patients (86 males and 63 females) were included in the study, aged (59.0±10.2) years. There were 27 patients (18.1%) who progressed to new-onset CKD 90 days after the occurrence of cardiac valve replacement surgery-associated AKI. Compared with non-CKD group, patients in CKD group had older age [66 (58, 70) vs 59 (53, 64) years], lower baseline eGFR [76.3 (65.8, 98.5) vs 92.7 (78.5, 101.6) ml·min·(1.73 m)], higher proportion of preoperative hypertension [51.9% (14/27) vs 27.9% (34/122)] and serum creatinine at discharge [136 (101, 165) vs 86 (65, 104) μmol/L], and the differences were statistically significant (all <0.05). The multivariate logistic regression analysis results revealed that older age (=1.063, 95%: 1.001-1.129, =0.047), preoperative hypertension (=3.070, 95%: 1.105-8.532, =0.031) and higher serum creatinine at discharge (=1.026, 95%:1.013-1.038, <0.001) were risk factors for progression to CKD in patients with cardiac valve replacement surgery-associated AKI. The clinical risk model including age, preoperative hypertension, preoperative baseline eGFR, and serum creatinine at discharge produced a moderate performance for predicting progression to CKD in patients with cardiac valve replacement surgery-associated AKI [the area under the curve (AUC)=0.865, 95% 0.790-0.940, <0.001]. Older age, preoperative hypertension and higher serum creatinine at discharge are risk factors for progression to CKD in patients with cardiac valve replacement surgery-associated AKI.
[Efficacy and safety of flexible ureteral lithotripsy for upper urinary tract calculi in patients aged 80 years and older]
Tang RH, Wang HR, Song LQ, Liu JY, Pang C and Wang JL
To assess the efficacy and safety of flexible ureteral lithotripsy (FURL) for treating upper urinary tract calculi in patients ≥80 years. This study retrospectively analyzed the clinical data of 297 elderly patients who underwent FURL for unilateral upper urinary tract calculi at Beijing Hospital from January 2019 to September 2023. Patients were divided into elderly group (≥80 years) and low-middle aged group (≥60-<80 years). Propensity score matching (PSM) was used to match preoperative clinical data of patients. After PSM, the basic, perioperative and postoperative data of the two groups were compared. After PSM, 116 patients were enrolled, including 58 patients in each group. The age [ (, )] of elderly group was 83.0 (81.0, 86.0) years, which included 29 males. The age of low-middle aged group was 69.5 (64.8, 74.0) years, which included 33 males. The duration of postoperative hospitalization [ (, )] in elderly group was longer than that in low-middle aged group [2 (1, 3) d vs 1 (1, 2) d, =0.002]. Serious postoperative complications occurred in 3 cases in the elderly group and 1 case in the low-middle aged group, respectively, without surgical intervention. There was no significant statistical difference in stone-free rate (SFR) [79.3% (46/58) vs 84.5% (49/58)], operation time [ (, ), 70.0 (48.3, 100.0) vs 65.0 (46.5, 101.2) min] and postoperative complication rate [25.9% (15/58) vs 22.4% (13/58)] between two groups (all >0.05). In the treatment of upper urinary tract calculi in patients ≥80 years, the SFR, operation time and postoperative complication rate of FURL are comparable to those in low-middle aged elderly patients. FURL has good safety and effectiveness in the treatment of upper urinary tract calculi in patients ≥80 years.
[Relationship between bioelectrical impedance analysis-derived fluid status and nutritional indicators and the prognosis in patients undergoing maintenance hemodialysis]
Li T, Wu BY, Chen FY, Liu K and Mao HJ
To explore the relationship between bioelectrical impedance analysis (BIA)-derived fluid status and nutritional indicators and the prognosis in patients undergoing maintenance hemodialysis (MHD). A retrospective cohort study was conducted. The clinical data of MHD patients in Jiangsu Province Hospital between January 2014 and December 2016 were analyzed. BIA data of healthy volunteers in Gulou District, Nanjing City, collected between April and October 2022, were used to determine the cut-off value of body cell mass index (BCMI). Referring to previous research, using 0.15 as the cut-off value for the ratio of overhydration and extracellular water (OH/ECW). The data were transformed into binary variables based on these cut-off values to categorize patients into different groups. Kaplan-Meier analysis was used to plot survival curves, and the Cox proportional hazards model was performed to analyze risk factors for all-cause mortality. A total of 706 MHD patients (407 males and 299 females) were included, aged (54±15) years. MHD patients were classified into four groups based on whether BCMI was<5.4 kg/m and OH/ECW was≥0.15, which included non-overhydration and non-malnutrition group, overhydration group, malnutrition group, and overhydration and malnutrition group, with 269, 186, 151, and 100 patients, respectively. During a median follow-up of [(, )] 33 (26, 37) months, 162 patients died. Kaplan-Meier analysis showed that the median survival periods of the four groups were 52 months (95%: 41-54 months), 46 months (95%: 44-49 months), 37 months (95%: 34-40 months), and 34 months (95%: 30-38 months), respectively, with a statistically significant difference (<0.001). The 1-year survival rates were 95.5%, 93.5%, 92.1%, and 88.0% (<0.001), respectively, and the 2-year mortality rates were 92.6%, 87.1%, 83.4%, and 77.0% (<0.001), respectively. Multivariate Cox regression analysis showed that compared with non-overhydration and non-malnutrition group, the risk of all-cause mortality increased by 1.18 times in the malnutrition group (=2.18, 95%: 1.29-3.71, =0.004), and by 1.59 times in the overhydration and malnutrition group (=2.59, 95%: 1.48-4.54, =0.001). BIA-derived fluid status and nutritional indicators are associated with the prognosis of MHD patients. Compared with patients without fluid overload and malnutrition, patients with malnutrition and fluid overload have an increased risk of all-cause mortality.
[The value of midnight 1 mg dexamethasone suppression test combined with ACTH stimulation test in the diagnosis of primary aldosteronism subtypes]
Qiu P, Zhang L, Jiang DY, Zang L, Guo QH, Lyu ZH and Mu YM
To explore the value of the midnight 1 mg dexamethasone suppression test combined with adrenocorticotropic hormone (ACTH) stimulation test in the diagnosis of primary aldosteronism (PA) subtypes. A cross-sectional study Clinical data of patients diagnosed with PA at the First Medical Center of Chinese PLA General Hospital from January 2020 to September 2022, who completed the midnight 1 mg dexamethasone suppression test combined with ACTH stimulation test, were analysed retrospectively. The clinical characteristics and trial results of patients with aldosterone-producing adenoma (APA) and idiopathic hyper aldosteronism (IHA)were compared. The efficacy of the midnight 1 mg dexamethasone suppression test combined with ACTH stimulation test in distinguishing APA and IHA was evaluated by drawing receiver operating characteristic (ROC) curves, and the cut-off value of the diagnostic indicator was determined with the maximum Youden index. A total of 82 patients with PA were included, including 43 males and 39 females, aged (50.8±11.4) years old. They were divided into APA group (=49) and IHA group (=33) based on PA subtype. There was no statistically significant difference in body mass index, systolic and diastolic blood pressure between the two groups (all >0.05). The blood potassium and orthostatic renin levels in the APA group were lower than those in the IHA group, and the differences were statistically significant (all P<0.001). The orthostatic plasma aldosterone concentration (PAC), orthostatic aldosterone to renin ratio (ARR), PAC before and after captopril challenge test(CCT), ARR after CCT, PAC before and after saline infusion test (SIT), and the proportion of unilateral lesions in the APA group were all higher than those in the IHA group, and the differences were statistically significant (all <0.001). After the midnight 1 mg dexamethasone suppression test combined with ACTH stimulation test (30, 60, 90, 120 min), the PAC and PAC/cortisol levels in the APA group were significantly higher than those in the IHA group (all <0.05). The PAC at 90 min showed the highest diagnostic capability according to the area under the ROC(AUC) (0.930,95%:0.874-0.986), and the Youden index was the highest at a PAC cut-off value of 39.05 ng/dl(0.766). The sensitivity and specificity for distinguishing APA from IHA were 91.8% and 84.8%, respectively. The midnight 1 mg dexamethasone suppression test with ACTH stimulation test could be useful for differentiating the subtypes of PA. Among them, the PAC and PAC/cortisol at 90 min showed best diagnostic efficacy.
[Exploration of the clinical transformation application of the artificial intelligence diagnosis system for bladder cancer based on cystoscopy]
Wu SX, Chen X, Hong GB, Xu SZ and Lin TX
This study aims to explore the possibility and bottleneck of clinical translation for an artificial intelligence (AI) diagnosis system for bladder cancer based on cystoscopy.We retrospectively collected videos of 101 bladder cancer patients from January to November 2023, at Sun Yat-sen Memorial Hospital, Sun Yat-sen University. Among these patients, with a median age of 63 years and 81.0% were male. The bladder cancer AI diagnosis system was utilized for diagnosis, and the accuracy of diagnoses from the videos was assessed. Additionally, a surgical evaluation scale was formulated to evaluate the quality of the videos, simulating clinical usage.The final test results showed a system sensitivity of 97.8%, a positive predictive value of 81.7%, specificity of 54.2%, and a negative predictive value of 92.3%. Furthermore, the surgical evaluation scale scores ranged from 3.96 to 4.69, indicating the feasibility of clinical application for this system.This study further quantitatively validated the accuracy of an artificial intelligence system using cystoscopy videos and assessed the potential for clinical application.
[Analysis of MTHFR gene variants in fifteen children with hyperhomocysteinemia]
Liu F, Liang LL, Qiu WJ, Zhang HW, Zhan X, Xu F, Zhang Y, Zhang JM, Yang SH and Han LS
The clinical manifestations, biochemical and metabolic data, genetic variations and treatment data of children with MTHFR gene variant induced hyperhomocysteinemia admitted to Hangzhou Children's Hospital and Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from November 2015 to September 2021 were analysed retrospectively. A total of 15 pediatric patients were included, including 10 males and 5 females, with onset ages ranging from 6 days to 18 years old and confirmed ages ranging from 40 days to 18 years old. One confirmed case was detected through neonatal screening, and the remaining 14 cases were all diagnosed through genetic diagnosis after onset. The main clinical manifestations were feeding difficulties, hypotonia, epilepsy, developmental delay. All patients had elevated levels of blood homocysteine, with blood homocysteine levels before and after treatment being (151.46±57.44) μmol/L and (69.96±32.88) μmol/L, significantly decreased after treatment compared with before treatment, with a statistically significant difference (<0.001). The blood methionine level before the treatment was 9.40 (6.20, 11.96) μmol/L, normal or slightly decreased compared to the reference range. The methionine level returned to normal after treatment. A total of 19 MTHFR gene variants were detected, with 6 being unreported variants and 13 being known variants. c.1316C>T (p.L439P) was the most common variant(16.6%,5/30). All the patients had varied neurological damages, with 7 patients improved after metabolic therapy by carnitine and folinic acid, 8 patients experiencing developmental delay, and 1 patient experiencing frequent epilepsy. The clinical manifestations of MTHFR gene variation-related hyperhomocysteinemia are complex and variable. Early-onset and homozygous variants often have a poor prognosis. Blood homocysteine, blood amino acid analysis, serum total homocysteine assay and gene testing are helpful for early diagnosis.
[Effects of tumor location and mismatch repair on clinicopathological features and survival for non-metastatic colon cancer: A retrospective, single center, cohort study]
Sun Z, Zhou WX, Li KX, Wu B, Lin GL, Qiu HZ, Niu BZ, Sun XY, Lu JY, Xu L and Xiao Y
To analyze the differences in clinicopathological features of colon cancers and survival between patients with right- versus left-sided colon cancers. This was a retrospective cohort study. Information on patients with colon cancer from January 2016 to August 2020 was collected from the prospective registry database at Peking Union Medical College Hospital . Primary tumors located in the cecum, ascending colon, and proximal two-thirds of the transverse colon were defined as right-sided colon cancers (RCCs), whereas primary tumors located in the distal third of the transverse colon, descending colon, or sigmoid colon were defined as left-sided colon cancers (LCCs). Clinicopathological features were compared using the χ test or Mann-Whitney test. Survival was estimated by Kaplan-Meier curves and the log-rank test. Factors that differed significantly between the two groups were identified by multivariate survival analyses performed with the Cox proportional hazards function. One propensity score matching was performed to eliminate the effects of confounding factors. The study cohort comprised 856 patients, with TNM Stage I disease, 391 (45.7%) with Stage II, and 336 (39.3%) with Stage III, including 442 (51.6%) with LCC and 414 (48.4%) with RCC and 129 (15.1%). Defective mismatch repair (dMMR) was identified in 139 patients (16.2%). Compared with RCC, the proportion of men (274/442 [62.0%] vs. 224/414 [54.1%], χ=5.462, =0.019), body mass index (24.2 [21.9, 26.6] kg/m vs. 23.2 [21.3, 25.5] kg/m, =78,789.0, <0.001), and well/moderately differentiated cancer (412/442 [93.2%] vs. 344/414 [83.1%], χ=22.266, <0.001) were higher in the LCC than the RCC group. In contrast, the proportion of dMMR (40/442 [9.0%] vs. 99/414 [23.9%], χ=34.721, <0.001) and combined vascular invasion (106/442[24.0%] vs. 125/414[30.2%], χ=4.186, =0.041) were lower in the LCC than RCC group. The median follow-up time for all patients was 48 (range 33, 59) months. The log-rank test revealed no significant differences in disease-free survival (DFS) (=0.668) or overall survival (OS) (=0.828) between patients with LCC versus RCC. Cox proportional hazards model showed that dMMR was significantly associated with a longer DFS (HR=0.419, 95%CI: 0.204‒0.862, =0.018), whereas a higher proportion of T3-4 (HR=2.178, 95%CI: 1.089‒4.359, =0.028), N+ (HR=2.126, 95%CI: 1.443‒3.133, <0.001), and perineural invasion (HR=1.835, 95%CI: 1.115‒3.020, =0.017) were associated with poor DFS. Tumor location was not associated with DFS or OS (all >0.05). Subsequent analysis showed that RCC patients with dMMR had longer DFS than did RCC patients with pMMR (HR=0.338, 95%CI: 0.146‒0.786, =0.012). However, the difference in OS between the two groups was not statistically significant (HR=0.340, 95%CI:0.103‒1.119, =0.076). After propensity score matching for independent risk factors for DFS, the log-rank test revealed no significant differences in DFS (=0.343) or OS (=0.658) between patients with LCC versus RCC, whereas patient with dMMR had better DFS (=0.047) and OS (=0.040) than did patients with pMMR. Tumor location is associated with differences in clinicopathological features; however, this has no impact on survival. dMMR status is significantly associated with longer survival: this association may be stronger in RCC patients.
[Chinese expert consensus for resection margin in rectal cancer surgery (2024 edition)]
Colorectal cancer is the second most common malignant tumor in China, with rectal cancer accounting for approximately 50% of all cases. While neoadjuvant therapy is essential for diagnosis and treatment, proctectomy with radical resection remains indispensable. Especially for middle and low rectal cancer, the length of the distal resection margin is critical for prognosis, organ preservation, and postoperative quality of life. However, determining a "safe" margin to ensure the radical resection (R0) while maximizing the function of the anal sphincter poses a significant challenge for surgeons. Aiming at this, we conducted a comprehensive review of authoritative guidelines and literature domestically and internationally. We divided the issues related to resection margin in proctectomy into three chapters: (1) the concept and definition of the resection margin; (2) the evaluation of the resection margin in preoperative, intra-operative, and post-operative stages; and (3) radical resection of rectal cancer after neoadjuvant therapy. With the help of the Delphi method, the expert group voted twice for 14 recommendations and finally established the "Chinese Expert Consensus for Resection Margin in Rectal Cancer Surgery (2024 version)". This consensus serves as a valuable reference for clinicians to carry out proctectomy of rectal cancer, which can improve patient's quality of life without affecting their prognosis.
[Retrospective study of role of neoadjuvant rectal scores in evaluating the 10-year disease-free survival of patients with locally advanced rectal cancer undergoing neoadjuvant chemoradiotherapy followed by surgery]
Zhang WL, Zhou C, Wang WF, Li WH, He JH, Lu ZH, Wu XJ, Lin JZ and Peng JH
To investigate the correlation between the neoadjuvant rectal (NAR) score and long-term survival in patients with locally advanced rectal cancer who have undergone neoadjuvant chemoradiotherapy. Clinical and pathological data of 487 patients diagnosed with rectal adenocarcinoma from October 2004 to April 2014 at Sun Yat-sen University Cancer Center who had received neoadjuvant chemoradiotherapy were retrospectively analyzed and the impact of NAR score on prognosis studied. Disease-free-survival (DFS) was calculated by the Kaplan-Meier method and survivals compared using the log-rank test. Cox models were used for univariate and multivariate analyses. Receiver operating characteristic curves were utilized to evaluate the predictive capability of NAR and tumor regression grade scores for the risk of 10-year postoperative recurrence and metastasis. The Delong test was employed to compare the diagnostic performance of the two scores. Of the 487 patients included in the study, 166 were men (34.1%). The median age was 56 years (interquartile range [IQR]: 46-63). All patients completed adequate preoperative chemoradiotherapy and underwent R0 resection.The median interval between the end of chemoradiotherapy and surgery was 51 days (IQR: 44-58). Post-chemoradiotherapy downstaging occurred in 329 patients (67.6%). Tumor regression grades (TRGs) were 1-2 in 246 patients (50.5%) and 3-4 in 241 patients (49.5%). A total of 394 patients (80.9%) received postoperative chemotherapy. NAR scores were <8 in 182 patients (37.4%), 8-16 in 180 (37.0%), and >16 in 125 (25.6%). The median follow-up time was 111.5 months (IQR: 70.7-133.7 months). One hundred and thirteen patients died of rectal cancer, among whom 13 patients developed local recurrence, 88 patients developed distant metastasis, and 12 patients had unknown recurrence patterns. The 10-year DFS and overall survival rate of f the whole group were 68.9% and 71.5% respectively. The 10-year DFS rates for patients with NAR scores <8, 8-16, and >16 were 85.1%, 80.5%, and 66.4%, respectively (<0.001). Multivariate analyses revealed that the Dixon operation (HR=0.606, 95%CI: 0.408-0.902, =0.014), and >16 (HR=2.569, 95%CI: 1.559-4.233, 0.001) were independent predictors of the 10-year DFS of patients with locally advanced rectal cancer (<0.05 for all). In the entire patient cohort, the AUC of the receiver operating characteristic curve for NAR score predicting 10-year recurrence and metastasis was 0.67 (95%CI: 0.62-0.72), whereas the AUC for TRG score was 0.54 (95%CI: 0.49-0.60). The two scores differed significantly in accuracy (=-4.06, <0.001), the NAR score being a significantly better predictor of risk of 10-year recurrence and metastasis than the TRG score. The NAR score is a reliable predictor of 10-year DFS in patients with locally advanced rectal cancer who have undergone neoadjuvant chemoradiotherapy followed by curative surgery.
[Multivariate analysis and construction and validation of a nomogram model from data of 1610 patients with non-tumor-related anastomotic stenosis after rectal cancer surgery]
Qiu KM, Jian W, Zheng JX, Feng MY, Liu XM, Lu DS and Yan J
To assess the risk factors affecting development of non-tumor- related anastomotic stenosis after rectal cancer and to construct a nomogram prediction model. This was a retrospective study of data of patients who had undergone excision with one-stage intestinal anastomosis for rectal cancer between January 2003 and September 2018 in Nanfang Hospital of Southern Medical University. The exclusion criteria were as follows: (1) pathological examination of the operative specimen revealed residual tumor on the incision margin of the anastomosis; (2) pathological examination of postoperative colonoscopy specimens revealed tumor recurrence at the anastomotic stenosis, or postoperative imaging evaluation and tumor marker monitoring indicated tumor recurrence; (3) follow-up time <3 months; and (4) simultaneous multiple primary cancers. Univariate analysis using the χ or Fisher's exact test was performed to assess the study patients' baseline characteristics and variables such as tumor-related factors and surgical approach (<0.05). Multivariate analysis using binary logistic regression was then performed to identify independent risk factors for development of non-tumor-related anastomotic stenosis after rectal cancer. Finally, a nomogram model for predicting non-tumor-related anastomotic stenosis after rectal cancer surgery was constructed using R software. The reliability and accuracy of this prediction model was evaluated using internal validation and calculation of the area under the curve of the model's receiver characteristic curve (ROC). The study cohort comprised 1,610 patients, including 1,008 men and 602 women of median age 59 (50, 67) years and median body mass index 22.4 (20.2, 24.5) kg/m². Non-tumor-related anastomotic stenosis developed in 121 (7.5%) of these patients. The incidence of non-tumor-related anastomotic stenosis in patients who had undergone neoadjuvant chemotherapy, neoadjuvant radiotherapy, and surgery alone was 11.2% (10/89), 26.4% (47/178), and 4.8% (64/1,343), respectively. Neoadjuvant treatment (neoadjuvant chemotherapy: OR=2.455, 95%CI: 1.148-5.253, =0.021; neoadjuvant chemoradiotherapy, OR=3.882, 95%CI: 2.425-6.216, <0.001), anastomotic leakage (OR=7.960, 95%CI: 4.550-13.926, <0.001), open laparotomy (OR=3.412, 95%CI: 1.772-6.571, <0.001), and tumor location (distance of tumor from the anal verge 5-10 cm: OR=2.381, 95%CI:1.227-4.691, <0.001; distance of tumor from the anal verge <5 cm: OR=5.985,95% CI: 3.039-11.787, <0.001) were identified as independent risk factors for non-tumor-related anastomotic stenosis. Thereafter, a nomogram prediction model incorporating the four identified risk factors for development of anastomotic stenosis after rectal cancer was developed. The area under the curve of the model ROC was 0.815 (0.773-0.857, <0.001), and the C-index of the predictive model was 0.815, indicating that the model's calibration curve fitted well with the ideal curve. Non-tumor-related anastomotic stenosis after rectal cancer surgery is significantly associated with neoadjuvant treatment, anastomotic leakage, surgical procedure, and tumor location. A nomogram based on these four factors demonstrated good discrimination and calibration, and would therefore be useful for screening individuals at risk of anastomotic stenosis after rectal cancer surgery.
[Application of D-type stoma repair in parastomal hernia after permanent sigmoidostomy]
Fu YY, Zhou JJ, Zhang CK, Sun LH, Wang W, Ren J, Wang LH, Tang D, Ma Y and Wang DR
[Influence of neoadjuvant chemoradiotherapy on peritoneal wound healing after abdominoperineal resection]
Wang G, Yao X, Wu YJ, Tao KX and Gao JB
To study the influence of neoadjuvant chemoradiotherapy on peritoneal wound recovery after abdominoperineal resection (APR). This was a retrospective cohort study of data of 219 patients who had been pathologically diagnosed with low rectal cancer and undergone APR in the Union Hospital of Tongji Medical College of Huazhong University of Science and Technology between January 2018 and December 2021. Of these patients, 158 had undergone surgery without any pre-surgical treatment (surgery group), 35 had undergone surgery after neoadjuvant chemotherapy (neoadjuvant chemotherapy group), and 26 had undergone surgery after neoadjuvant chemoradiotherapy (neoadjuvant chemoradiotherapy group). The primary outcome was perineal wound complications occurring within 30 days. The status of wound healing was classified into the following three levels: Level A: abnormal wound seepage that improved after wound discharge; Level B: wound infection and dehiscence; and Level C: Level B plus fever. The patients' general condition, tumor status, perianal wound healing level, and intra- and post-operative recovery were recorded. None of the study patients had any complications during surgery. The duration of surgery was 240.0 (180.0-300.0) minutes, 240.0 (225.0-270.0) minutes and 270.0 (240.0-356.2) minutes in the surgery, neoadjuvant chemotherapy, and neoadjuvant chemoradiotherapy groups, respectively (=6.508, =0.039). The rates of perineal wound complications were 34.6% (9/26) and (22.9%, 8/35)in the neoadjuvant chemoradiotherapy group and the neoadjuvant chemotherapy group, being significantly higher than that in the surgery group (10.1%, 16/158). After adjusting for patient age and sex using a logistic regression model, the risk of complications was still higher in the neoadjuvant chemoradiotherapy than in the surgery group (OR=4.6, 95%CI: 1.7-12.7; OR=2.6, 95%CI: 1.0-6.8), these differences being statistically significant (both <0.05). The duration of hospital stay was 9.5 (7.0-12.0) days, 10.0 (8.0-17.0) days and 11.5 (9.0-19.5) days for patients in the surgery, neoadjuvant chemotherapy, and neoadjuvant chemoradiotherapy groups, respectively (=0.569, =0.752). However, after adjusting for patient age and sex by using a generalized linear model, hospital stay was longer in the neoadjuvant chemoradiotherapy than in the surgery group (β [95% CI]: 4.4 [0.5-8.4], =0.028). After surgery, 155 of 219 patients required further adjuvant chemotherapy. A higher proportion of patients with than without wound complications did not attend for follow-up (32.2% [10/31] vs. 16.1% [20/124]); this difference is statistically significant (χ=4.133, =0.023). In patients with low rectal cancer, neoadjuvant radiotherapy may be associated with an increased risk of perineal wound infection and non-healing.
[Application of double transanal drainage tube in prevention of anastomotic leakage after laparoscopic anterior resection in patients with rectal cancer]
Sun SW, Zheng XY, Yu JT, Su C, Wang L, Liu CY, Sun C, Ju PF and Zhang HH
[Clinical application of modified abdominal transverse incision in colorectal cancer surger]
Ge XC, Li ZQ, Zhang JH and Xin Q
The evidence base for ICS/formoterol maintenance and reliever therapy in severe asthma
Beasley R, Noble J and Weatherall M
[Report on the application of endoscopic intermuscular dissection for diagnostic resection of early rectal cancer]
Fan DJ, Huang LY, Qi JW, Wu QN, Kong XH and Li CJ
This report presents the initial outcomes of endoscopic intermuscular dissection (EID), a novel technique introduced by our team for the diagnostic resection of early rectal cancer, focusing on the postoperative status of the vertical margins. On January 26, 2024, a patient with early rectal cancer (cT1-2N0M0) underwent Endoscopic Intermuscular Dissection. The EID procedure consists of six steps: (1) mucosal incision; (2) submucosal dissection; (3) superficial muscular layer incision; (4) intermuscular dissection; (5) complete tumor removal; (6) wound management. The patient was a 70-year-old male with rectal cancer (cT1-2N0M0). The tumor was located on the left anterior wall of the rectum, approximately 9 cm from the anal margin, and measured 20mm in size. The dissection rate was 2.68 mm²/minute, and the total duration of the surgery was 109 minutes. The patient was successfully discharged on the fifth day after surgery. Pathological examination of the post-endoscopic surgery specimen revealed pT1b, with negative vertical margins. Follow-up after more than one month showed good recovery with no complications such as bleeding, perforation, infection, or stricture occurring. Colonoscopy indicated the presence of a granulation tissue suggestive of inflammation. Endoscopic Intermuscular Dissection for the diagnostic resection of early rectal cancer is potentially safe and may achieve negative vertical margins.
Analysis of the impact of material properties on tabletability by principal component analysis and partial least squares regression
Mareczek L, Riehl C, Harms M and Reichl S
Principal component analysis (PCA) and partial least squares regression (PLS) were combined in this study to identify key material descriptors determining tabletability in direct compression and roller compaction. An extensive material library including 119 material descriptors and tablet tensile strengths of 44 powders and roller compacted materials with varying drug loads was generated to systematically elucidate the impact of different material descriptors, raw API and filler properties as well as process route on tabletability. A PCA model was created which highlighted correlations between different powder descriptors and respective characterization methods and, thus, can enable reduction of analyses to save resources to a certain extent. Subsequently, PLS models were established to identify key material attributes for tabletability such as density and particle size but also surface energy, work of cohesion and wall friction, which were for the first time demonstrated by PLS as highly relevant for tabletability in roller compaction and direct compression. Further, PLS based on extensive material characterization enabled the prediction of tabletability of materials unknown to the model. Thus, this study highlighted how PCA and PLS are useful tools to elucidate the correlations between powder and tabletability, which will enable more robust prediction of manufacturability in formulation development.
Hypogonadotropic hypogonadism with Zinner syndrome: a coincidence or a consequence?
Shah R, Mukherjee S, Bhadada SK and Walia R
This case report describes a man in his 20s presenting with bilateral crypto-orchidism, micropenis and underdeveloped secondary sexual characteristics. The patient also exhibited hyposmia, eunuchoid stature and gynecomastia. Biochemical investigations revealed low levels of testosterone, luteinising hormone and follicle-stimulating hormone. Hence, he was diagnosed with Kallmann syndrome. Imaging studies showed an absent right kidney and cystic dilatation of the distal ureteric bud, seminal vesicle and absent/hypoplastic ejaculatory duct. The association of hypogonadotropic hypogonadism with Zinner syndrome, a rare condition characterised by renal agenesis, seminal vesicle cyst and ejaculatory duct obstruction, was noted.
Improving medication safety in both adults and children: what will it take?
Bates DW and Sakuma M
Construction of an in vitro simulated one compartment extravascular administration model and its comparison with classic in vitro administration model in copper chloride induced HepG2 cell death
Yan L, Fu D, Chen J, Hao M, Fu J, Yao B, Hao W and Zhao P
In this study, we designed an in vitro administration device based on compartment model theory and utilized it to construct an in vitro simulated one compartment extravascular administration model of copper chloride. Within the C range of 3.91-1000.00 μM, the measured concentration-time curves of the simulated one compartment extravascular administration model almost coincide with the corresponding theoretical curves. The measured values of toxicokinetic parameters, including k, T, k, T, T, C, CL, and AUC are close to the corresponding theoretical values. The fitting coefficients are >0.9990. In simulated one compartment extravascular administration and classic in vitro administration, copper chloride dose-dependently induced HepG2 cell death. When C/administration concentration is equal, classic in vitro administration induces a higher cell death rate than simulated one compartment extravascular administration. However, there is no significant difference in inducing cell death between the two administration models when area under the curve is equal. In conclusion, the device designed in this study can be used to in vitro simulate one compartment extravascular administration, making in vitro toxicity testing more similar to in vivo scenarios. There are differences in copper chloride induced HepG2 cell death between simulated one compartment extravascular administration and classic in vitro administration.
Misidentification of as species: potential pitfalls in the diagnosis of brucellosis
Howley F, Abukhodair S, de Barra E, O'Connell K and McNally C
We describe a case of brucellosis in a man in his 20s, who presented to the emergency department with a 1-month history of fevers, dry cough and knee pain. Blood cultures were positive after 55 hours and was identified on matrix-assisted laser desorption/ionisation time of flight (MALDI-TOF) mass spectrometry. spp are Gram-negative organisms that are phylogenetically related to spp but commercially available MALDI-TOF libraries cannot distinguish between the two genera. Further positive blood cultures for combined with characteristic growth patterns for spp led to targeted questioning of the patient regarding potential exposure risks, which revealed a history of consumption of unpasteurised camel milk in the Middle East 3 months earlier. Treatment of brucellosis was initiated and subsequent whole genome sequencing identified the blood culture isolate as confirming the diagnosis of brucellosis. This case highlights the challenges in the diagnosis of brucellosis in low-incidence settings.
Cannabidiol protects mouse hippocampal neurons from neurotoxicity induced by amyloid β-peptide
Del Carmen Barboza Salgado K, de Freitas Nascimento RG, Coelho PJFN, Oliveira LAM and de Oliveira Pinto Coelho Nogueira K
Alzheimer's disease (AD), the most prevalent form of dementia worldwide, is a significant health concern, according to the World Health Organization (WHO). The neuropathological diagnostic criteria for AD are based on the deposition of amyloid-β peptide (Aβ) and the formation of intracellular tau protein tangles. These proteins are associated with several overlapping neurodegenerative mechanisms, including oxidative stress, mitochondrial dysfunction, lipid peroxidation, reduced neuronal viability, and cell death. In this context, our study focuses on the potential therapeutic use of cannabidiol (CBD), a non-psychotropic cannabinoid with antioxidant and anti-inflammatory effects. We aim to evaluate CBD's neuroprotective role, particularly in protecting hippocampal neurons from Aβ-induced toxicity. Our findings indicate that CBD significantly improves cell viability and decreases levels of lipid peroxidation and oxidative stress. The results demonstrate that CBD possesses a robust potential to rescue cells from induced neurotoxicity through its antioxidant properties. Additionally, the neuroprotective effect of CBD may be associated with the modulation of the endocannabinoid system. These findings suggest that CBD could be a promising compound for adjuvant treatments in neurodegenerative processes triggered by amyloid-β peptide.
H3K18 lactylation accelerates liver fibrosis progression through facilitating SOX9 transcription
Wu S, Li J and Zhan Y
Liver fibrosis is a significant health concern globally due to its association with severe liver conditions like cirrhosis and liver cancer. Histone lactylation has been implicated in the progression of hepatic fibrosis, but its specific role in liver fibrosis, particularly regarding H3K18 lactylation, remained unclear. To investigate this, we established in vivo and in vitro models of liver fibrosis using carbon tetrachloride (CCl4) injection in rats and stimulation of hepatic stellate cells (HSCs) with TGF-β1, respectively. We found that histone lactylation, particularly H3K18 lactylation, was upregulated in both CCl4-induced rats and TGF-β1-activated HSCs, indicating its potential involvement in liver fibrosis. Further experiments revealed that lactate dehydrogenase A (LDHA) knockdown inhibited H3K18 lactylation and had a beneficial effect on liver fibrosis by suppressing HSC proliferation, migration, and extracellular matrix (ECM) deposition. This suggests that H3K18 lactylation promotes liver fibrosis progression. Chromatin immunoprecipitation (ChIP) and luciferase reporter assays demonstrated that H3K18 lactylation facilitated the transcription of SOX9, a transcription factor associated with fibrosis. Importantly, overexpression of SOX9 counteracted the effects of LDHA silencing on activated HSCs, indicating that SOX9 is downstream of H3K18 lactylation in promoting liver fibrosis. In summary, this study uncovers a novel mechanism by which H3K18 lactylation contributes to liver fibrosis by activating SOX9 transcription. This finding opens avenues for exploring new therapeutic strategies for hepatic fibrosis targeting histone lactylation pathways.
Palmitic acid induces β-cell ferroptosis by activating ceramide signaling pathway
Guo M, Huang X, Zhang J, Huang Y, Tang Y, Wen H, Xu Y, Zhang S, Wei X, Sun S and Zhu Q
Individuals with type 2 diabetes mellitus frequently display heightened levels of palmitic acid (PA) in their serum, which may lead to β-cell damage. The involvement of ferroptosis, a form of oxidative cell death in lipotoxic β-cell injury remains uncertain. Here, we have shown that PA induces intracellular lipid peroxidation, increases intracellular Fe content and decreases intracellular glutathione peroxidase 4 (GPX4) expression. Furthermore, PA causes distinct changes in pancreatic islets and INS-1 cells, such as mitochondrial atrophy and increased membrane density. Furthermore, the presence of the ferroptosis inhibitor has a significant mitigating effect on PA-induced β-cell damage. Mechanistically, PA increased ceramide content and c-Jun N-terminal kinase (JNK) phosphorylation. The ceramide synthase inhibitor effectively attenuated PA-induced β-cell damage and GPX4/Fe abnormalities, while inhibiting JNK phosphorylation. Additionally, the JNK inhibitor SP600125 improved PA-induced cell damage. In conclusion, by promoting ceramide synthesis, PA inhibited GPX4 expression and increased intracellular Fe to induce β-cell ferroptosis. Moreover, JNK may be a downstream mechanism of ceramide-triggered lipotoxic ferroptosis in β-cells.
STIM1 Mediates Methamphetamine-Induced Neuronal Autophagy and Apoptosis
Tian Q, Zhou J, Xu Z, Wang B, Liao J, Duan K, Li X, Huang E and Xie WB
Methamphetamine (METH) is a widely abused amphetamine-type psychoactive drug that causes serious health problems. Previous studies have demonstrated that METH can induce neuron autophagy and apoptosis in vivo and in vitro. However, the molecular mechanisms underlying METH-induced neuron autophagy and apoptosis remain poorly understood. Stromal interacting molecule 1 (STIM1) was hypothesized to be involved in METH-induced neuron autophagy and apoptosis. Therefore, the expression of STIM1 protein was measured and the effect of blocking STIM1 expression with siRNA was investigated in cultured neuronal cells, and the hippocampus and striatum of mice exposed to METH. Furthermore, intracellular calcium concentration and endoplasmic reticulum (ER) stress-related proteins were determined in vitro and in vivo in cells treated with METH. The results suggested that STIM1 mediates METH-induced neuron autophagy by activating the p-Akt/p-mTOR pathway. METH exposure also resulted in increased expression of Orai1, which was reversed after STIM1 silencing. Moreover, the disruption of intracellular calcium homeostasis induced ER stress and up-regulated the expression of pro-apoptotic protein CCAAT/enhancer-binding protein homologous protein (CHOP), resulting in classic mitochondria apoptosis. METH exposure can cause neuronal autophagy and apoptosis by increasing the expression of STIM1 protein; thus, STIM1 may be a potential gene target for therapeutics in METH-caused neurotoxicity.
Improving quality of care by standardising patient data collection in electronic medical records in an oncology department in Spain
Alonso-Jáudenes Curbera G, Gómez-Randulfe Rodríguez MI, Alonso de Castro B, Silva Díaz S, Parajó Vázquez I, Gratal P, López López R and García Campelo R
Evaluation of quality of care in oncology is key in ensuring patients receive adequate treatment. American Society of Clinical Oncology's (ASCO) Quality Oncology Practice Initiative (QOPI) Certification Program (QCP) is an international initiative that evaluates quality of care in outpatient oncology practices.
Paediatric oral electrical burn
Chen HA, Yu YC and Chang CJ
Perspectives from the leadership of
van der Burg SH and Lotze MT
Epigenomic partitioning of a polygenic risk score for asthma reveals distinct genetically driven disease pathways
Stikker B, Trap L, Sedaghati-Khayat B, de Bruijn MJW, van Ijcken WFJ, de Roos E, Ikram A, Hendriks RW, Brusselle G, van Rooij J and Stadhouders R
Individual differences in susceptibility to develop asthma, a heterogeneous chronic inflammatory lung disease, are poorly understood. It remains debated whether genetics can predict asthma risk and how genetic variants modulate the complex pathophysiology of asthma.
Global herpes zoster burden in adults with asthma: a systematic review and meta-analysis
Mortimer KJ, Cruz AA, Sepúlveda-Pachón IT, Jorga A, Vroling H and Williams C
Asthma is a common respiratory disease, which may be associated with an increased risk of herpes zoster (HZ), often a debilitating disease associated with severe pain. This was the first systematic review with the objective of summarizing evidence on HZ burden in adults with asthma.
[A case of multiple primary hepatoid adenocarcinoma in the intestine]
Xie LF, Jia J, Liu Y and Li XY
Sex differences in asthma control, lung function and exacerbations: the ATLANTIS study
Kole TM, Muiser S, Kraft M, Siddiqui S, Fabbri LM, Rabe KF, Papi A, Brightling C, Singh D, van der Molen T, Nawijn MC, Kerstjens HAM and van den Berge M
Asthma is a heterogeneous disease with a prevalence and severity that differs between male and female patients.
Stealing Survival: Iron Acquisition Strategies of Mycobacterium tuberculosis
Shankar G and Akhter Y
Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), faces iron scarcity within the host due to immune defenses. This review explores the importance of iron for Mtb and its strategies to overcome iron restriction. We discuss how the host limits iron as an innate immune response and how Mtb utilizes various iron acquisition systems, particularly the siderophore-mediated pathway. The review delves into the structure and biosynthesis of mycobactin, a key siderophore in Mtb, and the regulation of its production. We explore the potential of targeting siderophore biosynthesis and uptake as a novel therapeutic approach for TB. Finally, we summarize current knowledge on Mtb's iron acquisition and highlight promising directions for future research to exploit this pathway for developing new TB interventions.
Re-vitalizing Wastewater: Nutrient Recovery and carbon capture through Microbe-Algae synergy using Omics-Biology
Malla MA, Ansari FA, Bux F and Kumari S
Increasing amounts of wastewater is the most pervasive and challenging environmental problem globally. Conventional treatment methods are costly and entail huge energy and carbon consumption and greenhouse gas emissions. Owing to their unique ability of carbon capturing and resource recovery, microalgae-microbiome based treatment is a potential approach and is widely used for carbon-neutral wastewater treatment. Microalgae-bacteria synergy (i.e., the functionally beneficial microbial synthetic communities) performs better and enhances carbon-sequestration and nutrient recovery from wastewater treatment plants. This review presents a comprehensive information regarding the potential of microalgae-microbiome as a sustainable agent for wastewater and discusses synergistic approaches for effective nutrient removal. Moreover, this review discusses, the role of omics-biology and Insilco approaches in unravelling and understanding the algae-microbe synergism and their response toward wastewater treatment. Finally, it discusses various microbiome engineering approaches for developing the effective microalgae-bacteria partners for carbon sequestration and nutrient recovery from wastewater, and summarizes future research perspectives on microalgae-microbiome based bioremediation.
Perinatal exposure to perfluorooctane sulfonate and the risk of hepatic inflammation in rat offspring: Perturbation of gut-liver crosstalk
Liu Y, Yu G, Medsker H, Luo T, Meng X, Wang C, Feng L and Zhang J
Perfluorooctane sulfonate (PFOS) exposure is associated with harmful hepatic outcomes. Growing evidence indicates that crosstalk between the gut microbiome, immune system, and liver plays a vital role in the pathogenesis of liver diseases. However, the underlying mechanism is not fully understood. In the present study, we aimed to investigate the effects of PFOS exposure during pregnancy and lactation on hepatic inflammation in rat offspring. Features of hepatic inflammation and increased levels of aspartate-amino transferase (AST) were found in pups on postnatal day 28 (PND28) in PFOS-exposed groups. Gut microbiota analysis identified Chitinophaga, Ralstonia, and Alloprevotella as the key genera in distinguishing the PFOS-exposed group from the control group. Metabolic and transcriptomic analyses found that PFOS exposure resulted in 48 differentially expressed metabolites (DEMs) in the serum, 62 DEMs in the liver, and 289 differentially expressed genes (DEGs) in the liver of PND28 pups. The immune response is significantly enriched in PFOS-exposed liver on PND28; multi-omics analysis indicated that PFOS might lead to immune response perturbation by disturbing the metabolic profiling in the liver. The changed gut microbiota was significantly related to the serum level of the liver function index. Specifically, Alloprevotella, Chitinophage, Ruminococcus, and Allobaculum were significantly associated with the metabolic abundance changes of 4-Hydroxydebrisoquine, L-Norvaline, and Eremopetasinorol, and the gene expression changes of Acat211, Msmol, Idi1, Sqle, and Gadd45b in the liver. These findings suggest that early-life PFOS exposure may be associated with adverse hepatic inflammation in young offspring via disruption of the gut-liver crosstalk, which may provide mechanistic clues for clarifying the hepatotoxicity in offspring associated with perinatal PFOS exposure.
Clinical remission with biologic therapies in severe asthma: a matter of definition
, McDowell PJ, McDowell R, Busby J, Eastwood MC, Patel PH, Jackson DJ, Mansur A, Patel M, Burhan H, Doe S, Chaudhuri R, Gore R, Dodd JW, Subramanian D, Brown T and Heaney LG
Severe non-hepatic hyperammonaemic encephalopathy in an immunocompromised adolescent with enterocolitis
Borrie AE, Pike M, Villeneuve S and Verma N
Non-hepatic causes of hyperammonaemia are uncommon relative to hepatic aetiologies. An adolescent female was admitted to the hospital with a diagnosis of very severe aplastic anaemia. During her treatment with immunosuppressive therapy, she developed neutropenic enterocolitis, pseudomonal bacteraemia and hyperammonaemia. A combination of intermittent haemodialysis and high-volume continuous veno-venous haemodiafiltration (CVVHDF) was required to manage the hyperammonaemia. Despite a thorough investigation, there were no hepatic, metabolic or genetic aetiologies identified that explained the hyperammonaemia. The hyperammonaemia resolved only after the surgical resection of her inflamed colon, following which she was successfully weaned off from the renal support. This is a novel case report of hyperammonaemia of non-hepatic origin secondary to widespread inflammation of the colon requiring surgical resection in an immunocompromised patient. This case also highlights the role of high-volume CVVHDF in augmenting haemodialysis in the management of severe refractory hyperammonaemia.
ANCA negative pulmonary vasculitis: a challenging diagnosis
Zhang Y, Mayor K and Mahdi A
A man in his 40s with end-stage kidney disease due to IgA nephropathy and receiving peritoneal dialysis presented with a 1-week history of breathlessness, cough and nosebleeds. CT scan of the chest revealed ground glass changes while blood tests indicated elevated inflammatory markers and a negative vasculitis screen. This included negative ANCA and anti-GBM antibodies. Initial treatment for suspected atypical pneumonia with antibiotics yielded no clinical improvement.Over the course of the admission, his symptoms progressively worsened, leading to oxygen dependency with a FiO2 of 40% and episodes of haemoptysis. Suspicions of pulmonary vasculitis arose due to clinical deterioration, prompting consultation with a tertiary vasculitis centre. It was subsequently concluded that the clinical and radiological findings correlated with ANCA-negative pulmonary vasculitis or a rare case of IgA-associated pulmonary capillaritis. Treatment with methylprednisolone and rituximab led to significant improvement, allowing rapid oxygen withdrawal. The patient was discharged with a tapering prednisolone regimen.
A Qualitative Examination of a Reminiscence Intervention for Older Adults Using Three-Dimensional (3D) Printed Objects
Anderson KA, Berg-Weger M, Olofinboba O and Plocher T
Reminiscence has been found to be an effective therapy for older adults and researchers and practitioners have identified a range of benefits, from cognitive stimulation to the reconciliation of past experiences. In this qualitative study, the authors explore the experiences of older adults engaged in a technology-enhanced form of reminiscence therapy (RT) using three-dimensional (3D) printed objects from peoples' past. Content analysis of individual interviews with seven participants ( = 7) revealed three themes: (1) positive experiences with the RT intervention; (2) reflections on the use of 3D printed objects; and (3) the development of relationships between participants and researchers. These findings suggest that RT using 3D printed objects can be effective, but only if objects are accurate and if it suits participants' personalities. Researchers and practitioners may find that the use of 3D printed objects can enhance their RT interventions and thereby enrich the lives of older adults.
Brachial plexopathy as a complication of axillary artery aneurysm in a case of Takayasu arteritis
Siddiqui A, Vijayvergia P, Kishor K and Kumar P
Takayasu arteritis is an inflammatory disease of unknown aetiology affecting large vessels. Medium vessel involvement is also well documented; however, neuropathy as a presenting manifestation is rare. In this case report, a young woman in her 20s presented with an 8-month history of intermittent claudication in the right upper limb progressing to rest pain with allodynia in C5-C8 distribution and painless right axillary mass. On examination, she had absent pulses in the right radial, brachial and subclavian artery with audible bruit in the right subclavian and abdominal aorta. CT angiogram showed features suggestive of Takayasu arteritis with a partially thrombosed aneurysm arising from the right axillary artery leading to compression of the right brachial plexus. This patient received treatment with methotrexate and oral corticosteroids. At 3 months follow-up, there was a reduction in the size of the aneurysm, resolution of compressive symptoms and normalisation of inflammatory markers.
Precision Medicine to Redefine Insulin Secretion and Monogenic Diabetes-Randomized Controlled Trial (PRISM-RCT) in Chinese patients with young-onset diabetes: design, methods and baseline characteristics
O CK, Fan YN, Fan B, Lim C, Lau ESH, Tsoi STF, Wan R, Lai WY, Poon EW, Ho J, Ho CCY, Fung C, Lee EK, Wong SY, Wang M, Ozaki R, Cheung E, Ma RCW, Chow E, Kong APS, Luk A and Chan JCN
We designed and implemented a patient-centered, data-driven, holistic care model with evaluation of its impacts on clinical outcomes in patients with young-onset type 2 diabetes (T2D) for which there is a lack of evidence-based practice guidelines.
Junior doctors offer prime minister "final chance" to avoid pre-election strike
Iacobucci G
Social media: Add tobacco-style warnings to protect children, says US surgeon general
Tanne JH
GPs unable to find new posts despite shortages, says royal college
O'Dowd A
GP who confronted Rishi Sunak received "hundreds" of supportive messages from doctors
Feinmann J
Exploring the minimal important difference in the treatment of paediatric obsessive-compulsive disorder using selective serotonin reuptake inhibitors
Cohen SE, Denys DAJP, Mattila TK, Storosum BWC, de Boer A and Zantvoord JB
Consultant who submitted false job references is struck off
Dyer C
Use of a Sengstaken-Blakemore tube in a lifesaving non-variceal oesophageal bleed from pseudoaneurysms of the superior and inferior thyroid arteries
Ng DCY and Lim KT
Assessing the use of sodium-glucose cotransporter 2 inhibitor in patients with type 2 diabetes mellitus and chronic kidney disease in tertiary care: a SwissDiab Study
Hösli PS, Renström F, Laimer M, Cavelti-Weder C, Gastaldi G, Lehmann R and Brändle M
The overall aim of this study was to evaluate the implementation of sodium-glucose cotransporter 2 inhibitors (SGLT2i) among patients in tertiary care with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD).
Synthesis and characterization of Pyrus communis fruit extract synthesized ZnO NPs and assessed their anti-diabetic and anti-microbial potential
Elankathirselvan K, Fathima H A, K P and Al-Ansari MM
The fruit Pyrus communis, owing to its presence of phenolics and flavonoids, was chosen for its nanoparticle's reducing and stabilizing properties. Furthermore, the zinc metal may be nano-absorbed by the human body. As a result, the study involves synthesizing zinc oxide nanoparticles (ZnO NPs) from P. communis fruit extract using the green method. The synthesized nanoparticle was examined with a UV-visible spectrophotometer, Fourier Transform Infrared Spectroscopy (FTIR), Scanning Electron Microscopy (SEM), and Dynamic Light Scattering (DLS). When absorption studies were performed with a UV-visible spectrophotometer, the nanoparticle exhibited a blue shift. The FTIR spectrum revealed the molecular groups present in both the fruit extract and metal. In the SEM analysis, the ZnO NPs appeared as spherical particles, agglomerated together, and of nano-size. The larger size of the ZnO NPs in DLS can be attributed to their ability to absorb water. After characterization, nanoparticles were tested for anti-diabetic (α-amylase and yeast glucose uptake activity) and anti-microbial properties. The α-amylase inhibition percentage was 46.46 ± 0.15% for 100 μg/mL, which was comparable to the acarbose inhibition percentage of 50.58 ± 0.67% at the same concentration. The yeast glucose uptake activity was 64.24 ± 0.80% at 20 mM glucose concentration, which was comparable to the standard of 78.03 ± 0.80. The nanoparticle was more effective against Gram-negative bacteria Shigella sp. and Salmonella typhi than against Gram-positive bacteria Bacillus cereus and Streptococcus pneumoniae.
Viscoelastic testing guided coagulation management in factor VII deficiency for spinal anaesthesia and caesarean section
Yoon U, Haley S, Huffnagle S and Huffnagle J
The risks and benefits of spinal anaesthesia must be assessed in patients with coagulation disorders. A woman in her 20s with congenital factor VII (FVII) deficiency (31%) was admitted at 38 weeks for caesarean delivery. A rotational thromboelastometry (ROTEM) analysis showed normal coagulation and spinal anaesthesia was performed safely. A repeated ROTEM analysis after haemostasis and uterine closure showed normal coagulation without fibrinolysis. No prophylactic FVII was administered, resulting in a cost savings of US$12 884. FVII level did not predict bleeding or fibrinolysis and FVII and tranexamic acid were not indicated.
Bizarre parosteal osteochondromatous proliferation (Nora lesion) involving the spine: a case report and systematic review
Chen C, Wei B, Liu S, Shao Z and Chen S
Bizarre parosteal osteochondromatous proliferation (BPOP), also termed Nora lesion, is a rare, benign tumor most often located in the hands and feet. We herein present the second reported case of BPOP affecting the spine, an uncommon location. One year after surgical excision, the patient was pain-free and showed no evidence of recurrence. We reviewed a total of 323 cases of BPOP among 101 articles, providing the first systematic update on the latest knowledge of BPOP. The age of patients with BPOP ranges from 3 months to 87 years, peaking in the second and third decades of life. The hands are the most common location of BPOP (58.39%), followed by the feet (20.81%). Imaging features play a key role in the diagnosis of BPOP, but histopathologic diagnosis remains the gold standard. Differential diagnosis of BPOP should be based on the epidemiologic and clinical features as well as clinical examination findings. Surgical resection is the most extensively used treatment for BPOP. Recurrence is common (37.44%) and can be treated with re-excision. This article can deepen our understanding of BPOP and will be helpful for the diagnosis and treatment of BPOP in clinical practice.
Can the Cartilaginous Thickness Determine the Risk of Malignancy in Pelvic Cartilaginous Tumors, and How Accurate is the Preoperative Biopsy of These Tumors?
Laitinen MK, Parry MC, Morris GV, Kurisunkal V, Stevenson JD and Jeys LM
Peripheral osteochondral tumors are common, and the management of tumors presenting in the pelvis is challenging and a controversial topic. Some have suggested that cartilage cap thickness may indicate malignant potential, but this supposition is not well validated.
Coastal aquatic pollutants degradation using ZnCoO nanorods
Gnanasekaran L, Ramalingam G, Suresh R, Nangan S, Zielińska-Jurek A, Chen WH and Soto-Moscoso M
Water pollution has caused problems in coastal areas, rivers, lakes, and other important water sources around the world as a result of inappropriate waste management. Meanwhile, these pollutants are harmful to humans and aquatic life. Textile dye effluent methyl orange (MO) was used in this work for dye degradation studies employing nanocomposites. As a result, the importance of synthesizing pure ZnO and CoO nanoparticles with composites of ZnCoO (zinc cobaltite) nanorods in three various proportions (90:10, 75:25, and 50:50) is emphasized in this study. Many advanced approaches were used to assess the various features of these materials, including size and shape. Fourier transform infrared (FT-IR) spectroscopy was used to determine the vibrational modes of the materials. The absorption measurements were then carried out using UV-vis spectroscopic techniques, and the photocatalytic breakdown of MO was done under visible light irradiation. The findings revealed that pure materials were inadequate for visible light activity, resulting in decreased degradation efficiencies. Spinel cobaltite structures have potential degradation efficiency under visible light, while ZnCoO (50:50) catalyst has superior degradation efficiency of 59.8% over MO. The crystallite size, morphology, functional group, absorption wavelength, and band gap all play important roles in enhancing the material's photocatalytic activity under visible light. Meanwhile, ZnCoO spinel structures are crucial for increasing charge carriers and reducing electron-hole recombination. As a result, zinc cobaltite minerals are widely used in industrial dye degradation applications.
Bio-fabrication of calcium oxide nanoparticles from Coccinia grandis as a potential photocatalyst for dye degradation with antimicrobial activity
Brindhadevi K, M R, Albeshr MF and Pallath N
In the current study, Coccinia grandis fruit extract was used to synthesize calcium oxide nanoparticles (CaO NPs) in an economical and environmentally friendly manner. UV-Vis spectroscopy and Fourier transform infrared spectroscopy revealed that the phytoconstituents found in Coccinia grandis fruit extract facilitated the production of CaO NPs by acting as better stabilizing, biodegradable, and reducing agents. The synthesized CG-CaO NPs were also tested for photocatalytic activity in the breakdown of selective dyes such as methyl red, methyl orange, and methylene blue in the presence of sunlight. The degradation percentage was determined by analyzing the color removal rates for all dye components. After 6 h of reaction, the IC values for methyl red, methyl orange, as well as methylene blue dyes were 73, 107, and 133, respectively. The CG-CaO NPs were further evaluated for their antimicrobial activity against specific bacteria and fungi using the agar-well diffusion method. 200 μg mL CG-CaO NPs inhibited Aspergillus niger, Escherichia coli, Salmonella typhi, Streptococcus mutans, and Staphylococcus aureus at zones of 13, 14, 16, 14, and 15 mM, respectively. Further checkerboard assay confirmed the antagonism effect with gentamicin. Also, Artemia salina toxicity assay showed that the LD50 value of CaO NPs was 400 μg/mL of CaO NPs. The findings confirm that Coccinia grandis-mediated CG-CaO NPs can be used effectively in antimicrobial and environmental settings.
Long-term discontinuation of warfarin in a patient with HeartMate 3 left ventricular assist device without thromboembolic events
Dharuman Y, Doss M, Risteski P and Popov AF
The gold standard therapy for end-stage heart failure is cardiac transplantation. However, in the face of a donor shortage, a mechanical assist device such as the left ventricular assist device HeartMate 3 (Abbott Laboratories, Abbott Park, IL, USA) serves as bridging therapy to transplantation and/or destination therapy. Current guidelines recommend anticoagulation with a vitamin K antagonist in combination with low-dose aspirin. We herein report a challenging anticoagulation regimen in a patient with a HeartMate 3 in whom systemic anticoagulation with warfarin was not feasible for 4 years because of low compatibility and a rare X-factor deficiency. This is a rare hematological disorder, estimated to affect approximately 1 in every 500,000 to 1,000,000 people in the general population. The patient finally received a modified anticoagulation regimen involving the combination of rivaroxaban and clopidogrel without warfarin. Under this regimen, the patient remained free of thromboembolic complications for 4 years with placement of the left ventricular assist device. This case illustrates that under specific circumstances, long-term absence of warfarin therapy is feasible in patients with a HeartMate 3.
Exploring Spatiotemporal Patterns of Algal Cell Density in Lake Dianchi with Explainable Machine Learning
Tao Y, Ren J, Zhu H, Li J and Cui H
The escalating global occurrence of algal blooms poses a growing threat to ecosystem services. In this study, the spatiotemporal heterogeneity of water quality parameters was leveraged to partition Lake Dianchi into three clusters. Considering water quality parameters and both the delayed and instantaneous effects of meteorological factors, ensemble learning, and quasi-Monte Carlo methods were employed to predict daily algal cell density (AD) between January 2021 and January 2024. Consistently, superior predictive accuracy across all three clusters was exhibited by the Stacking-Elastic-Net regularization model. Furthermore, the minimum combination of drivers that achieved near-optimal accuracy for each cluster was identified, striking a balance between accuracy and cost. The ranking of the effect of drivers on AD varied by cluster, while the delayed effect of meteorological factors on AD generally outweighed their instantaneous effect for all clusters. Additionally, the heterogeneous or homogeneous thresholds and responses between drivers and AD were explored. These findings could serve as a scientific and cost-effective basis for government agencies to develop regional sustainable strategies for managing water quality.
Exposure to Residential Greenness, Perceived Stress, and Depressive Symptoms in a North American Preconception Cohort
Reimer CJ, Willis MD, Wesselink AK, Hystad P, Campbell EJ, Hatch EE, Kirwa K, Gradus JL, Vinceti M, Wise LA and Jimenez MP
/Aims: Studies suggest that greater exposure to natural vegetation (i.e., greenness) is associated with better mental health. However, there is limited research on greenness and mental health in the preconception period, a critical window of exposure in the life course. We investigated the associations of residential greenness with perceived stress and depressive symptoms using cross-sectional data from a cohort of pregnancy planners.
Mediation of FOXA2/IL-6/IL-6R/STAT3 signaling pathway mediates benzo[a]pyrene-induced airway epithelial mesenchymal transformation in asthma
Tang L, Chen B, Wang B, Xu J, Yan H, Shan Y and Zhao X
Benzo[a]pyrene (BaP), a toxic pollutant, increases the incidence and severity of asthma. However, the molecular mechanisms underlying the effects of BaP in asthma remain unclear. In terms of research methods, we used BaP to intervene in the animal model of asthma and the human bronchial epithelial (16HBE) cells, and the involved mechanisms were found from the injury, inflammation, and airway epithelial to mesenchymal transition (EMT) in asthma. We also constructed small interfering RNAs and overexpression plasmids to knockdown/overexpress IL-6R and FOXA2 in 16HBE cells and a serotype 9 adeno-associated viral vector for lung tissue overexpression of FOXA2 in mice to determine the mechanism of action of BaP-exacerbated asthma airway EMT. We observed that BaP aggravated inflammatory cell infiltration into the lungs, reduced the Penh value, increased collagen fibres in the lung tissue, and increased serum IgE levels in asthmatic mice. After BaP intervention, the expression of FOXA2 in the lung tissue of asthmatic mice decreased, the production and secretion of IL-6 were stimulated, and STAT3 phosphorylation and nuclear translocation increased, leading to changes in EMT markers. However, EMT decreased after increasing FOXA2 expression and decreasing that of IL-6R and was further enhanced after low FOXA2 expression. Our results revealed that BaP exacerbated airway epithelial cell injury and interfered with FOXA2, activating the IL-6/IL-6R/STAT3 signaling pathway to promote airway EMT in asthma. These findings provide toxicological evidence for the mechanism underlying the contribution of BaP to the increased incidence of asthma and its exacerbations.
Biochar derived from animal and plant facilitates synergistic transformation of heavy metals and phosphorus in sewage sludge composting
Zhao M, Zhong S, Zhou X and Yu Z
This study investigated the influence of plant-derived biochar (PB) and animal-derived biochar (AB) on behavior of heavy metals and phosphorus fractions during sewage sludge composting. PB was highly effective in reducing the bioavailability of Zn and Cu by 39% and 50%, respectively, while AB decreased the bioavailability of Pb (30%) and Cd (12%). Both biochar increased available phosphorus by over 38%. Acid extractable and bioavailable Pb in AB, and water-soluble, oxidizable and total Zn, acid extractable and oxidizable Cu in PB were positively correlated with moderately resistant organic phosphorus (MROP). Besides, in AB, Cd had strong and positive correlation with highly resistant organic phosphorus (HROP). This suggested biochar facilitated the formation of stable organometallic complexes through binding metal ions to phosphorus fractions, with notable differences based on biochar source. FT-IR showed biochar promoted humification, with PB enhancing carboxyl and polysaccharide formation, while AB encouraged quinone and aryl ether structures. These surface functional groups on the biochar likely contributed to heavy metals and phosphorus binding through chelation, adsorption, and electron shuttling.
Trace elements alone or in mixtures associated with unconventional natural gas exploitation affect rat fetal steroidogenesis and testicular development in vitro
Baalbaki G, Lim V, Gillet AP, Verner MA, Vaillancourt C, Caron-Beaudoin E and Delbes G
Biomonitoring studies have shown that pregnant women living in regions of unconventional natural gas (UNG) exploitation have higher levels of trace elements. Whether developmental endocrine disruption can be expected at these exposure levels during pregnancy is unclear. In this study, we aimed to test the impact of five trace elements alone or in mixtures using in vitro cell- and tissue-based assays relevant to endocrine disruption and development. Manganese, aluminum, strontium, barium, and cobalt were tested at concentrations including those representatives of human fetal exposure. Using transactivation assays, none of the tested elements nor their mixture altered the human estrogen receptor 1 or androgen receptor genomic signalling. In the rat fetal testis assay, an organ culture system, cobalt (5 μg/l), barium (500 μg/l) and strontium (500 μg/l) significantly increased testosterone secretion. Cobalt and strontium were associated with hyperplasia and/or hypertrophy of fetal Leydig cells. Mixing the five elements at concentrations where none had an effect individually stimulated testosterone secretion by the rat fetal testis paralleled by the significant increase of 3β-hydroxysteroid dehydrogenase protein level in comparison to the vehicle control. The mechanisms involved may be specific to the fetal testis as no effect was observed in the steroidogenic H295R cells. Our data suggest that some trace elements in mixture at concentrations representative of human fetal exposure can impact testis development and function. This study highlights the potential risk posed by UNG operations, especially for the most vulnerable populations, pregnant individuals, and their fetus.
Evidence of size-dependent toxicity of polystyrene nano- and microplastics in sea cucumber Apostichopus japonicus (Selenka, 1867) during the intestinal regeneration
Liu J, Chen Y, Song Y, Xu D, Gu Y, Wang J, Song W, Sun B, Jiang Z and Xia B
Microplastics are ubiquitous pollutants in the global marine environment. However, few studies have adequately explored the different toxic mechanisms of microplastics (MPs) and nanoplastics (NPs) in aquatic organisms. The sea cucumber, Apostichopus japonicus, is a key organism in the marine benthic ecosystem due to its crucial roles in biogeochemical cycles and food web. This study investigated the bioaccumulation and adverse effects of polystyrene micro- and nanoplastics (PS-M/NPs) of different sizes (20 μm, 1 μm and 80 nm) in the regenerated intestine of A. japonicus using multi-omics analysis. The results showed that after 30-day exposure at the concentration of 0.1 mg L, PS-MPs and PS-NPs accumulated to 155.41-175.04 μg g and 337.95 μg g, respectively. This excessive accumulation led to increased levels of antioxidases (SOD, CAT, GPx and T-AOC) and reduced activities of immune enzymes (AKP, ACP and T-NOS), indicating oxidative damage and compromised immunity in the regenerated intestine. PS-NPs had more profound negative impacts on cell proliferation and differentiation compared to PS-MPs. Transcriptomic analysis revealed that PS-NPs primarily affected pathways related to cellular components, e.g., ribosome, and oxidative phosphorylation. In comparison, PS-MPs had greater influences on actin-related organization and organic compound metabolism. In the PS-M/NPs-treated groups, differentially expressed metabolites were mainly amino acids, fatty acids, glycerol phospholipid, and purine nucleosides. Additionally, microbial community reconstruction in the regenerated intestine was severely disrupted by the presence of PS-M/NPs. In the PS-NPs group, Burkholderiaceae abundance significantly increased while Rhodobacteraceae abundance decreased. Correlation analyses demonstrated that intestinal regeneration of A. japonicus was closely linked to its enteric microorganisms. These microbiota-host interactions were notably affected by different PS-M/NPs, with PS-NPs exposure causing the most remarkable disruption of mutual symbiosis. The multi-omic approaches used here provide novel insights into the size-dependent toxicity of PS-M/NPs and highlight their detrimental effects on invertebrates in M/NPs-polluted marine benthic ecosystems.
Randomized Clinical Trial to Compare Three Fluoride Varnishes in Preventing Early Childhood Caries
Manchanda S, Liu P, Sardana D, Peng S, Lo EC and Yiu CK
To compare the effectiveness of two 5% sodium fluoride (NaF) varnishes containing casein phosphopeptide amorphous calcium phosphate (CPP-ACP) (Clinpro White) or tricalcium phosphate (TCP) (MI Varnish ) to the conventional 5% NaF varnish (Duraphat®) in preventing early childhood caries (ECC) in high-risk preschool children.
Posterior two-unit cantilevered zirconia resin-bonded fixed partial dentures: A 3-year prospective single-arm clinical trial
Lam WYH, Lim TW, Yon MJY, Chau JMH, Lai GCH, Wang DCP and Botelho MG
To evaluate the longevity of cantilevered zirconia-based resin-bonded fixed partial dentures (RBFPDs) in replacing missing posterior teeth, as well as the quality of life and patient satisfaction experienced by those receiving zirconia RBFPDs.
Cohort profile: understanding health service system needs for people with intellectual disability using linked data in New South Wales, Australia
Reppermund S, Srasuebkul P, Vajdic CM, Pearson S, Moorin RE and Trollor JN
This cohort profile describes one of the largest linked datasets in the world concerning the health of people with intellectual disability. The cohort comprises a retrospective group of 100,089 individuals with intellectual disability who received disability and/or health services in New South Wales, Australia. Of these participants, 34% were female, with a median age at cohort entry of 3 years (interquartile range, 0 to 19 years). A separate comparator cohort included 455,677 individuals, matched by 5-year age group, sex, and residential postcode at a 5:1 ratio. Initial results indicate that between 2001 and 2018, people with intellectual disability experienced more than double the rate of hospitalisations (538 versus 235 per 1000 person-years), as well as markedly higher rates of emergency department presentations (707 versus 379 per 1000 person-years) and use of ambulatory mental health services (1012 versus 157 per 1000 person-years), relative to the comparator cohort. The largest disparities in hospital admissions were for mental disorders, dialysis, and diseases of the nervous system and sense organs. Furthermore, individuals with intellectual disability had more than double the rate of dispensed medications found in the comparator cohort. Of these medications, 46.6% were for the treatment of nervous system conditions, as opposed to 24.7% for the comparator cohort. The mean age at death was 52 years (standard deviation [SD], 19 years) for people with intellectual disability and 64 years (SD, 22 years) for the comparator participants.
Uterus Transplantation: A Future Issue for the French Legislator?
Bérar A, Marcucci L and Bouvet R
Uterus transplantation (UT) is a surgical procedure that seeks to correct absolute uterine infertility. As such, it is coupled with assisted reproductive technologies (ART). Currently performed as an investigational procedure in France, this technique could be subject to a legal framework in the future. Given its specificities, the French legislator will need to state their position on several matters. Regarding the donor, they will need to determine whether the benefits for the infertile woman justify exposure of a living person to the risks of the removal procedure. If necessary, they will have full freedom to set the criteria for selecting the living donor based on age, the existence or not of past pregnancies or the nature of the donor-recipient relationship. On the other side, the conditions for becoming a recipient should be consistent with the existing rules for ART. Other considerations could include age and past pregnancies again. Lastly, the legislator will also need to address the possible desire for UT without the endpoint of pregnancy.
Motivations for completing pulmonary rehabilitation - A qualitative analysis
Harvey J, Ingram K, Edwards G, Jenkins TO, Gardener G, Patel S, Man WD and Barker RE
Previous studies have focused on demographic factors that might predict non-completion of pulmonary rehabilitation (PR). We aimed to identify key modifiable factors that promote completion of PR. A mixed methods survey was offered to participants completing a discharge assessment following PR. Descriptive statistics and inductive thematic analysis were used to analyse the survey responses, with investigator triangulation. 62 of 187 (33%) patients attending a PR discharge assessment between November 2022 and April 2023 returned the anonymised survey. Desire to improve health and wellbeing was the main reason for both initially committing to a course and for continuing with PR past transient thoughts of leaving. The positive impact of staff was the second most common reason. The enjoyment of the PR programme, being held accountable to attend classes, and the importance of other group members were other key themes identified. In conclusion, our findings suggest PR services need to implement strategies which ensure regular promotion and reinforcement of the health benefits of PR as well as implementation of PR modalities which best monopolise on the positive impact skilled staff have on motivating patients to complete PR.
[The temporary polyclinic in the Olympic Village]
Bourgninaud M, Le Van P and de La Brière A
The Olympic and Paralympic Games are a sporting event that welcomes more than ten thousand top-level athletes. These athletes require daily care before and after training and competition, but are also prone to serious injuries. The polyclinic, set up in the athletes' village, will provide a wide range of high-quality care for the various delegations. Urgent care will be provided by the hospitals of the Assistance publique-Hôpitaux de Paris, which are responsible for the administration of the polyclinic.
Exploring the relationship between oxidative stress status and inflammatory markers during primary Sjögren's syndrome: A new approach for patient monitoring
Benchabane S, Sour S, Zidi S, Hadjimi Z, Nabila L, Acheli D, Bouzenad A, Belguendouz H and Touil-Boukoffa C
Primary Sjögren's syndrome (pSS) is a chronic inflammatory disease primarily affects exocrine glands dysfunction. Oxidative stress (OS) is a phenomenon occurring as a result of an imbalance between the generation of free radicals and antioxidant defense system. Hence, we aimed to establish the status of OS and inflammatory response according to the pSS disease activity index. In this context, we investigated malondialdehyde (MDA), and antioxidant enzymes during pSS. The possible association between MDA and nitric oxide (NO) levels and between MDA and some pro-inflammatory cytokines (IL-1β, IL-6, TNF-α, and IL-33).
[Athletes' sleep]
Chennaoui M
Sport and sleep are linked: practising sport favours good sleep, and sufficient sleep favours performance. Sleep deprivation increases the risk of injury and slows recovery from injury.
Increased plasma levels of N-terminal pro-B-type natriuretic peptide as biomarker for the diagnosis of cardioembolic ischaemic stroke
García-Carmona JA, Conesa-García E, Vidal-Mena D, González-Morales M, Ramos-Arenas V, Sánchez-Vizcaíno-Buendía C, Soria-Torrecillas JJ, Pérez-Vicente JA and García-de-Guadiana-Romualdo L
Despite comprehensive study, the aetiology of stroke is not identified in 35% of cases.
[Water quality and athletes' health: One hundred years on, swimming is once again possible in the Seine]
Mauger M
A great deal of work has been undertaken to ensure that certain swimming events (open water and triathlon) at the Olympic and Paralympic Games can be held in the Seine under sanitary conditions that respect the health of the athletes. They will be the first to take the plunge in this river, but the aim is to speed up the process of making it possible for the people of Ile-de-France to swim in it too, as well as in the Marne.
[Nursing care for top-level athletes at Insep]
Dounias I, Huard M and Morel C
At the Institut national du sport, de l'expertise et de la performance, the aim of the nursing team of three nurses who have been working there since 2014, 2022 and 2023 is to provide the best possible support for these top athletes. Their work is divided into several tasks: medical surveillance, prevention, stress and hypoxia tests and day-to-day care.
[From immersion to inclusion, a learning experience]
Bizié H, Jaouën A, Quelhas I, Valle A and Coquet F
As part of their training, volunteer nursing students from the Gers healthcare training institute were invited to take part in a sports exchange with a handibasket team. The main aim of the project was to change their perceptions of disability. Here, four of the students share their experiences and the benefits of the experience.
[Nutrition and mental health in athletes]
Grimaud É
In the world of top-level sport, optimising athletic performance does not rely solely on physical training. Taking into account the intestine-brain axis offers new ways of optimising sports preparation, partly thanks to the role of the intestinal microbiota on performance and well-being.
Preliminary outcomes of endovascular treatment of moyamoya disease
Li XY, Tian YY, Li CH, Wang JW, Li H, Liu JF and Gao BL
This study aimed to investigate the effectiveness and safety of endovascular revascularisation of intracranial artery occlusion and stenosis in moyamoya disease using stent angioplasty.
[Caregiver-patient communication: A complex process]
Forest B
Caregiver-client communication is a process influenced by many specific elements arising from the context, the content and the form of the message, but also from the inner life of the patient and the caregiver. All these specific factors have an impact on the transmission and reception of the message.
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