Cancer and Psychiatry

There are substantial challenges in studying human transgenerational epigenetic outcomes resulting from environmental conditions. The task requires specialized methods and tools that incorporate specific knowledge of multigenerational relationship combinations of probands and their ancestors, phenotype data for individuals, environmental information of ancestors and their descendants, which can span historical to present datasets, and informative environmental data that chronologically aligns with ancestors and descendants over space and time. As a result, there are few epidemiologic studies of potential transgenerational effects in human populations, thus limiting the knowledge of ancestral environmental conditions and the potential impacts we face with modern human health outcomes. In an effort to overcome some of the challenges in studying human transgenerational effects, we present two transgenerational study designs: transgenerational space-time cluster detection and transgenerational case-control study design. Like other epidemiological methods, these methods determine whether there are statistical associations between phenotypic outcomes (e.g., adverse health outcomes) among probands and the shared environments and environmental factors facing their ancestors. When the ancestor is a paternal grandparent, a statistically significant association provides some evidence that a transgenerational inheritable factor may be involved. Such results may generate useful hypotheses that can be explored using epigenomic data to establish conclusive evidence of transgenerational heritable effects. Both methods are proband-centric: They are designed around the phenotype of interest in the proband generation for case selection and family pedigree creation. In the examples provided, we incorporate at least three generations of paternal lineage in both methods to observe a potential transgenerational effect.

Cancer survivors experience barriers to primary healthcare (PHC) services. The aim was to explore reactions to and opinions about perceived challenges associated with PHC access and quality among cancer survivors in Sweden, including how they have acted to adapt to challenges.

Electronic (e-)cigarettes may help adult cigarette smokers achieve cigarette cessation, depending on patterns of e-cigarette use. Among cigarette smokers who do not use e-cigarettes, it is unclear if and how a-priori intentions for use are related to uptake patterns. Longitudinal studies have focused on established e-cigarette users or adolescent and young adult populations exclusively.

Neuropsychiatric symptoms in N-methyl-d-aspartate receptor encephalitis (NMDARE) have led some to pursue empiric trials of electroconvulsive therapy (ECT). A scoping review identified 39 patients diagnosed with NMDARE undergoing ECT. Separately, a retrospective cohort was reviewed to characterize 21 patients. Clinical improvement was attributed to ECT in 49% of patients in the scoping review and 19% of patients in the retrospective cohort; timing of immunotherapies was a confounding factor. Worsening of clinical course following ECT was reported in 28% of patients in the scoping review and 38% of patient in the retrospective review. There is currently insufficient data supporting a beneficial effect of ECT in NMDARE.

Caregivers of adults with cancer often report significant distress yet remain difficult to engage in supportive services. While the field of Psychosomatic Medicine has continued to identify important markers of physiologic stress, and demonstrated disruption in these markers in caregiver populations, no research has investigated whether biomarker information on caregivers' reaction to stress could impact their willingness to address their ongoing distress.

Research into the shared and distinct brain dysfunctions in patients with schizophrenia (SCZ) and major depressive disorder (MDD) has been increasing. However, few studies have explored the application of functional near-infrared spectroscopy (fNIRS) in investigating brain dysfunction and enhancing diagnostic methodologies in these two conditions.

Coronavirus disease 2019 (COVID-19) is a respiratory infection that considerably impacts both physical and mental health. In particular, the prolonged nature of psychological issues associated with COVID-19 has become a concern. However, evidence based on longitudinal studies investigating the changes in fear of COVID-19 has been limited, posing a public health challenge.

In recent decades, there has been increasing biomedical and public understanding of the role of autoimmunity in neuropsychiatric illness. Popular media have highlighted patients with psychiatric illnesses who were eventually diagnosed with autoimmune neuropsychiatric illnesses such as anti N-methyl-D-aspartate receptor encephalitis. Coverage of these cases has often drawn attention to the effects of misdiagnosis or delayed diagnosis of such diseases in psychiatric patients. Autoimmune encephalitis can have varied presentations and often involves evaluation and management from multiple medical specialties. As a result, there remains considerable uncertainty regarding how courts might gauge the legal standard of care with regard to psychiatric workup of new-onset psychiatric symptoms, and the degree to which autoimmune encephalitis must be considered. In this article we provide a brief overview of autoimmune encephalitis and autoimmune psychosis, including current diagnostic approaches to these conditions. We review case law regarding the standard of care for psychiatric disorders caused by general medical conditions. Finally, we provide a medicolegal perspective on the responsibilities of psychiatrists and other mental health professionals in the evaluation of possible autoimmune encephalitis.

Metabolic Syndrome (MetS) is a constellation of risk factors including abdominal obesity, high triglycerides, low HDL cholesterol (HDL-C), elevated blood pressure, and elevated fasting glucose. In Spain, according to WHO criteria, the MetS prevalence is shown to be 32% in men and 29% in women. The role of dietary habits is one of the main therapeutic strategies for the management of MetS but the most effective dietary pattern has not been established yet. This study aimed to analyze the effect of on body composition, serum lipids, and MetS components of a high-MUFA and high-fiber diet (HMFD). A case-control study was performed considering 40 cohabiting women. Participants were randomly assigned to HMFD group or high mono-unsaturated diet (HMD) group to receive one of the two proposed dietary interventions. All data (serum lipids, blood pressure, height, weight, body composition, and waist circumference) were collected fasting at baseline, 55, 98, and 132 days. The HMFD group showed higher decrease in waist circumference than in the HMD group. LDL-C dropped in both groups. Triglycerides in the HMFD group dropped during the intervention, but once the intervention was over, they returned to baseline values. The mean systolic blood pressure was lower in HMFD group. A HMFD from a weekly consumption of processed meat (Torrezno de Soria) deeply fried in extra virgin olive oil in combination with vegetables logged in a Mediterranean diet can improve MetS risk factors in healthy overweight women.

Polymorphisms in IL1B play a significant role in depression, multiple inflammatory-associated disorders, and susceptibility to infection. Functional non-synonymous SNPs (nsSNPs) result in changes in the encoded amino acids, potentially leading to structural and functional alterations in the mutant proteins. So far, most genetic studies have concentrated on SNPs located in the IL1B promoter region, without addressing nsSNPs and their association with multifactorial diseases. Therefore, this study aimed to explore the impact of deleterious nsSNPs retrieved from the dbSNP database on the structure and functions of the IL1B protein.

Sepsis constitutes a condition that involves life-threatening organ dysfunction induced by severe infection. This nested case-control study investigated risk factors for severe sepsis and whether antipsychotic use is associated with severe sepsis risk in patients with schizophrenia, a topic that has not been comprehensively explored in previous studies.

Glycophagy has evolved from an alternative glycogen degradation pathway into a multifaceted pivot to regulate cellular metabolic hemostasis in peripheral tissues. However, the pattern of glycophagy in the brain and its potential therapeutic impact on ischemic stroke remain unknown. Here, we observed that the dysfunction of astrocytic glycophagy was caused by the downregulation of the GABA type A receptor-associated protein like 1 (GABARAPL1) during reperfusion in ischemic stroke patients and mice. PI3K-Akt pathway activation is involved in driving GABARAPL1 downregulation during cerebral reperfusion. Moreover, glycophagy dysfunction-induced glucosamine deficiency suppresses the nuclear translocation of specificity protein 1 and TATA binding protein, the transcription factors for GABARAPL1, by decreasing their O-GlcNAcylation levels, and accordingly feedback inhibits GABARAPL1 in astrocytes during reperfusion. Restoring astrocytic glycophagy by overexpressing GABARAPL1 decreases DNA damage and oxidative injury in astrocytes and improves the survival of surrounding neurons during reperfusion. In addition, a hypocaloric diet in the acute phase after cerebral reperfusion can enhance astrocytic glycophagic flux and accelerate neurological recovery. In summary, glycophagy in the brain links autophagy, metabolism, and epigenetics together, and glycophagy dysfunction exacerbates reperfusion injury after ischemic stroke.

The geriatric failure to thrive, a controversial French concept not present in the international literature, was first characterized by Jean Carrié in 1956. It is described as a process of aging and physical and psychological decline associated with advanced age, manifesting as a pronounced overall deterioration. In this case report, we present the case of an 88-year-old patient, admitted to a general medicine service for geriatric failure to thrive, whose management eventually leads to the diagnosis of endocarditis with digestive cancer complicated by a characterized depressive episode. This case prompts us to consider the geriatric failure to thrive with extreme caution and challenges the legitimacy of such a diagnosis in the context of an aging population and the progress of medical sciences.

Medial temporal lobe atrophy has been linked to decline in neuropsychological measures of explicit memory function. While the hippocampus has long been identified as a critical structure in learning and memory processes, less is known about contributions of the amygdala to these functions. We sought to investigate the relationship between amygdala volume and memory functioning in a clinical sample of older adults with and without cognitive impairment.

Engagement in physical activity (PA) is often associated with better sleep quality and less pain severity among patients diagnosed with breast cancer. However, less research has focused on whether patients' PA prior to breast surgery, including their perceived decrease in PA level, is associated with worse preoperative sleep quality, and subsequently, greater postoperative pain. This longitudinal study investigated whether patients' preoperative PA was associated with their postoperative pain. We also explored whether preoperative sleep disturbance partially mediated the relationship between preoperative PA and postoperative pain.

The Ras-induced ERK pathway (Raf-MEK-ERK signaling cascade) regulates a variety of cellular responses including cell proliferation, survival, and migration. Activating mutations in RAS genes, particularly in the KRAS gene, constitutively activate the ERK pathway, resulting in tumorigenesis, cancer cell invasion, and metastasis. DA-Raf1 (DA-Raf) is a splicing isoform of A-Raf and contains the Ras-binding domain but lacks the kinase domain. Consequently, DA-Raf antagonizes the Ras-ERK pathway in a dominant-negative manner and can serve as a tumor suppressor that targets mutant Ras protein-induced tumorigenesis. We show here that MEK inhibitors and DA-Raf interfere with the in vitro collective cell migration and invasion of human KRAS-mutant carcinoma cell lines, the lung adenocarcinoma A549, colorectal carcinoma HCT116, and pancreatic carcinoma MIA PaCa-2 cells. DA-Raf expression was silenced in these cancer cell lines. All these cell lines had high collective migration abilities and invasion properties in Matrigel, compared with nontumor cells. Their migration and invasion abilities were impaired by suppressing the ERK pathway with the MEK inhibitors U0126 and trametinib, an approved anticancer drug. Expression of DA-Raf in MIA PaCa-2 cells reduced the ERK activity and hindered the migration and invasion abilities. Therefore, DA-Raf may function as an invasion suppressor protein in the KRAS-mutant cancer cells by blocking the Ras-ERK pathway when DA-Raf expression is induced in invasive cancer cells.

Symptoms of cancer-related fatigue (CRF) can have a significant impact on patients' quality of life and treatment adherence. We aimed to investigate the relationship between CRF and multiple psychosocial and somatic indicators within a large mixed cancer sample.

Human spaceflight has historically been managed by government agencies, such as the NASA Twins Study, but new commercial spaceflight opportunities have opened spaceflight to a broader population. In 2021, the SpaceX Inspiration4 mission launched the first-ever all civilian crew to low Earth orbit, which included the youngest American astronaut (age 29), novel in-flight experimental technologies (handheld ultrasound imaging, smartwatch wearables, and immune profiling), ocular alignment measurements, and new protocols for in-depth, multi-omic molecular and cellular profiling. Here we report the primary findings from the 3-day spaceflight mission, which induced a broad range of physiological and stress responses, neurovestibular changes indexed by ocular misalignment, and altered neurocognitive functioning, some of which match long-term spaceflight, but almost all of which did not differ from baseline (pre-flight) after return to Earth. Overall, these preliminary civilian spaceflight data suggest that short-duration missions do not pose a significant health risk, and moreover present a rich opportunity to measure the earliest phases of adaptation to spaceflight in the human body at anatomical, cellular, physiologic, and cognitive levels. Finally, these methods and results lay the foundation for an open, rapidly expanding biomedical database for astronauts, which can inform countermeasure development for both private and government-sponsored space missions.

Chimeric antigen receptor (CAR) T-cell therapy provides promising outcomes in relapsed/refractory B acute lymphoblastic leukemia (ALL), yet still carries high toxicity rates and relatively poor long-term survival. Efficacy has yet to be demonstrated in other diagnoses while toxicity and risk profiles remain formidable. To date, treatment-related symptom burden is gleaned from clinical trial toxicity reports; the patient perspective remains understudied.

Allogeneic hematopoietic stem cell transplantation (HSCT) survivors experience significant psychological distress and low levels of positive psychological well-being, which can undermine patient-reported outcomes (PROs), such as quality of life (QoL). Hence, we conducted a pilot randomized clinical trial to assess the feasibility and preliminary efficacy of a telephone-delivered positive psychology intervention (Positive Affect for the Transplantation of Hematopoietic stem cells intervention [PATH]) for improving well-being in HSCT survivors.

Determining whether patients' unrealistic expectations of chemotherapy as a cure were associated with their perception of the disclosure of incurability.

Nearly one fifth of patients with venous thromboembolism (VTE) have cancer. When both of these conditions occur, especially in cases of cerebral vein thrombosis (CVT), patient management is often challenging. The aim of this study was to compare the characteristics and event courses in patients affected by CVT with and without cancer. Consecutive patients with CVT from the ACTION-CVT cohort study were included if cancer status was reported. Risk factors as well as the clinical and radiological characteristics of patients were compared. Univariable and multivariable analyses were performed to assess variables associated with cancer. Kaplan-Meier method and log-rank test, logistic regression analysis, and propensity score matching were used to investigate any association between cancer-related CVT and study outcomes (primary outcome at 3-months: recurrent VTE or major hemorrhage; recurrent VTE; major hemorrhage; recanalization status; all-cause-death). Overall, 1,023 patients with CVT were included, of which 6.5% had cancer. Older age (adjusted odds ratio [aOR] 1.28 per decade increase; 95% confidence interval [CI] 1.08-1.52) and absence of headache (aOR 0.47; 95% CI 0.27-0.84) were independently associated with cancer. Patients with cancer had a higher risk of recurrent VTE or major hemorrhage (aOR 3.87; 95% CI 2.09-7.16), all-cause-death (aOR 7.56 95% CI 3.24-17.64), and major hemorrhage (aOR 3.70 95% CI 1.76-7.80). Recanalization rates, partial or complete, was not significantly different. CVT patients with cancer were more likely to be older, have no referred headache, and have worse outcomes compared to CVT patients without cancer.

Qualitative research has explored how some testicular cancer survivors (TCS) experience the psychological impacts of diagnosis and treatment. More research into the impacts of testicular cancer (TC) on adolescent and young adults (AYA) is needed due to the critical period of identity development. The present study aimed to explore how AYA with TC appraise and make sense of their experience and to develop a greater understanding of psychosexual identity development in AYA TCS.

Mentoring is vital to career development in academic medicine, and communication underlies all aspects of the mentoring relationship. Although training research mentors has been shown to be effective, few academic medicine faculties have received training in how to mentor. The investigators developed a novel intervention, the Mentor Communication Skills Training for Oncology Faculty ("Comskil Mentor Training") and examined feasibility and preliminary efficacy.

In 2013, afatinib was approved for non-small-cell lung cancer with subsequent indication expansion. We investigated published afatinib clinical trials to assess risk and benefit profiles for the drug in its approved indication of non-small-cell lung cancer as well as in off-label uses. Previous literature demonstrates excessive patient burden and limited benefit as afatinib has spread into more indications. A trial analysis is needed to establish efficacy and risk.

This Committee Report provides methodological, interpretive, and reporting guidance for researchers who use measures of heart rate (HR) and heart rate variability (HRV) in psychophysiological research. We provide brief summaries of best practices in measuring HR and HRV via electrocardiographic and photoplethysmographic signals in laboratory, field (ambulatory), and brain-imaging contexts to address research questions incorporating measures of HR and HRV. The Report emphasizes evidence for the strengths and weaknesses of different recording and derivation methods for measures of HR and HRV. Along with this guidance, the Report reviews what is known about the origin of the heartbeat and its neural control, including factors that produce and influence HRV metrics. The Report concludes with checklists to guide authors in study design and analysis considerations, as well as guidance on the reporting of key methodological details and characteristics of the samples under study. It is expected that rigorous and transparent recording and reporting of HR and HRV measures will strengthen inferences across the many applications of these metrics in psychophysiology. The prior Committee Reports on HR and HRV are several decades old. Since their appearance, technologies for human cardiac and vascular monitoring in laboratory and daily life (i.e., ambulatory) contexts have greatly expanded. This Committee Report was prepared for the Society for Psychophysiological Research to provide updated methodological and interpretive guidance, as well as to summarize best practices for reporting HR and HRV studies in humans.

Tapentadol is a drug of choice for neuropathic cancer pain. questionnaire quickly determines neuropathic pain component. The aim of this study is to determine the correlation between neuropathic malignant pain component by applying tapentadol antidolorose pharmacotherapy in combination with palliative radiotherapy of osseous neuropathic metastatic changes in breast cancer patients before and after palliative radiotherapy. The first patients group comprised 30 patients with primary breast cancer and proved painful bone secondary deposits with neuropathy for which tapentadol was prescribed, and they underwent palliative radiotherapy. The second group comprised 30 patients with primary breast cancer and proved painful bone metastases with neuropathy treated only with palliative antidolorose radiotherapy. : After two-months-follow up, tapentadol group patients had lower DN4 score values (Z=2,021; p=0.043). Significantly lower number of tapentadol group patients was without neuropathic pain after a three-month-follow up (χ ²=5,711; p=0.017). Significantly greater number of tapentadol group patients had best ECOG score 0 ( χ² =7,486; p=0.023). There was statistically significant positive correlation between tapentadol dose and DN4 score in patients after a month (ρ=0,471; p=0.009) and three months after the radiotherapy completion (ρ=0,610; p<0.001). Tapentadol is an opioid analgesic efficient for neuropathy relief in these patients and DN4 questionnaire is an efficient pharmacotherapy tool.

To assess sex-specific differences in the association between pre-transfusion haemoglobin values and early neurodevelopmental function.

There are limited data available, particularly in low- and middle-income countries (LMICs), on the long-term quality of life (QoL) and family functioning of primary caregivers of children and young people (CYPs) affected by primary brain tumors (PBTs). This study aimed to assess the factors associated with the mean change in QoL and family functioning scores of primary caregivers of CYP patients with PBTs 12 months posttreatment.

Cigarette smoking prevalence has declined slower among women than men, and smoking-related pulmonary disease (PD) has risen dramatically among women. Given these trends, there is a critical need to understand and mitigate PD risk among women who smoke. The purpose of this narrative review and commentary is to highlight important evidence from the literature on smoking and PD among women.

Young adult (YA) cancer survivors are a growing, yet underserved population who often face significant and long-lasting cancer-related physical (e.g., pain, fatigue) and emotional (e.g., psychological distress) symptoms. Post-treatment symptoms can persist, disrupting YA's abilities to complete goals consistent with their developmental stage (e.g., completing their education, achieving autonomy and independence, building their careers, establishing peer and romantic relationships, building their families). While symptom management has been identified as a significant issue in YA's transitions to survivorship, the symptom management needs of this population largely go unmet.

Caring for a person with a cancer diagnosis is challenging, especially for nursing students at the beginning of their professional careers. Although there has been previous research on the experiences of students in oncology units, there have been none to date on their experiences in a psycho-oncology unit. In this qualitative study, we evaluated the experiences of nursing students practicing in a psycho-oncology unit.

Establishing cost-effective informal care services for lonely older adults living at home in developing countries can be an innovative approach for improving their well-being. This study investigated the effectiveness of an informal home care support intervention program (HoSIP) reducing the loneliness and improving quality of life of lonely community-dwelling older adults.

Insomnia and repetitive negative thinking (RNT) are both prevalent among cancer survivors, yet little work has investigated their interrelationship. To explore the hypothesis that RNT and insomnia are related, we conducted secondary analyses on data from a pilot clinical trial of cognitive behavioral therapy for insomnia (CBT-I) for cancer survivors.

Understanding the shared and divergent mechanisms across antidepressant (AD) classes and probiotics is critical for improving treatment for mood disorders. Here we examine the transcriptomic effects of bupropion (NDRI), desipramine (SNRI), fluoxetine (SSRI) and a probiotic formulation (Lacidofil®) on 10 regions across the mammalian brain. These treatments massively alter gene expression (on average, 2211 differentially expressed genes (DEGs) per region-treatment combination), highlighting the biological complexity of AD and probiotic action. Intersection of DEG sets against neuropsychiatric GWAS loci, sex-specific transcriptomic portraits of major depressive disorder (MDD), and mouse models of stress and depression reveals significant similarities and differences across treatments. Interestingly, molecular responses in the infralimbic cortex, basolateral amygdala and locus coeruleus are region-specific and highly similar across treatments, whilst responses in the Raphe, medial preoptic area, cingulate cortex, prelimbic cortex and ventral dentate gyrus are predominantly treatment-specific. Mechanistically, ADs concordantly downregulate immune pathways in the amygdala and ventral dentate gyrus. In contrast, protein synthesis, metabolism and synaptic signaling pathways are axes of variability among treatments. We use spatial transcriptomics to further delineate layer-specific molecular pathways and DEGs within the prefrontal cortex. Our study reveals complex AD and probiotics action on the mammalian brain and identifies treatment-specific cellular processes and gene targets associated with mood disorders.

To investigate gender-specific factors associated with case complexity in a population-based sample of middle-aged and older adults using a holistic approach to complexity.

Drug-resistant epilepsy (DRE) affects about one-third of people with epilepsy (PWE). Our study aims to estimate the DRE prevalence and its predictive factors in Morocco. A cross-sectional study was conducted over 18 months. PWE with clinical diagnosis of epilepsy, and with an antiseizure treatment duration >12 months were examined in the neurology, neurosurgery, psychiatry, and pediatrics departments, of different sampled clinical sectors for the Casablanca-Settat region. Sociodemographic and clinical data were collected using a questionnaire during consultations. Antiseizure multi-therapy, a seizure freedom duration <12 months, compliance, and adequate posology were the determining factors for classifying DRE. Data were analyzed using Statistical Package for Social Sciences (SPSS) software, version 21.0. Statistical significance was set at p < 0.05 and logistic regression was performed to determine the predictive factors. In our sample of 446 PWE, the median age is 25 years (IQR: 11.75-44.00). The DRE estimated prevalence was 29.4 %. Pseudo-resistant epilepsy (PRE) was 18.0 %. Multivariate logistic regression analysis reports that single marital status (ORa = 1.94; CI95%: 1.02-3.71), comorbidities and concomitant affections (ORa = 2.14; CI95%: 1.27-3.59), structural etiology (ORa = 1.96; CI95%: 1.16-3.30), pre-ictal aura (ORa = 1.90; CI95%: 1.09-3.29), inter-ictal EEG abnormalities (ORa = 2.45; CI95%: 1.24-4.84) and allopathic treatment use (ORa = 2.10; CI95%: 1.30-3.39) are the predictive factors for DRE. We report an alarming DRE prevalence. Associated factors found may contribute to the prognosis and early management. PWE awareness, facilitating healthcare access and the development of epilepsy surgery are the key points to limit DRE in Morocco and prevent its various complications, especially for the pediatric population.

Treatment of locally advanced rectal cancer (LARC) involves neoadjuvant chemoradiotherapy plus total mesorectal excision and adjuvant chemotherapy. However, total neoadjuvant therapy (TNT) protocols (ie, preoperative chemotherapy in addition to radiotherapy) may allow better adherence and early treatment of distant micrometastases and may increase pathological complete response (pCR) rates.

Stroke is the leading cause of adult-onset disability. Although clinical factors influence stroke outcome, there is a significant variability among individuals that may be attributed to genetics and epigenetics, including DNA methylation (DNAm). We aimed to study the association between DNAm and stroke prognosis.

Thyroid carcinoma ranks as the 9th most prevalent global cancer, accounting for 586,202 cases and 43,636 deaths in 2020. Computerized image analysis, utilizing artificial intelligence algorithms, emerges as a potential tool for tumor evaluation.

Patients with cancer-related pain are at high risk for aberrant drug use behaviors (ADB), including self-escalation, diversion and concurrent illicit substance or opioid misuse; however, limited evidence is available to guide opioid prescribing for patients with life-limiting illness and concurrent or suspected ADB. We sought to characterize how specialists evaluate for and manage these high-risk behaviors in patients with cancer-related pain.

By analyzing 15,000 samples from 348 mammalian species, we derive DNA methylation (DNAm) predictors of maximum life span ( = 0.89), gestation time ( = 0.96), and age at sexual maturity ( = 0.85). Our maximum life-span predictor indicates a potential innate longevity advantage for females over males in 17 mammalian species including humans. The DNAm maximum life-span predictions are not affected by caloric restriction or partial reprogramming. Genetic disruptions in the somatotropic axis such as growth hormone receptors have an impact on DNAm maximum life span only in select tissues. Cancer mortality rates show no correlation with our epigenetic estimates of life-history traits. The DNAm maximum life-span predictor does not detect variation in life span between individuals of the same species, such as between the breeds of dogs. Maximum life span is determined in part by an epigenetic signature that is an intrinsic species property and is distinct from the signatures that relate to individual mortality risk.

Communication in oncology was challenging long before the emergence of the US 21st Century Cures Act. Before 2021, a growing body of evidence had demonstrated the benefits of patients' access to and review of the clinical notes in their charts (open notes); however, studies examining the benefits of immediate access to test results were scarce until the implementation of the Cures Act's Information Blocking Rule. Individuals grappling with cancer today now possess immediate access to their laboratory results, imaging scans, diagnostic tests, and progress notes as mandated by law. To many clinicians, the implementation of the Cures Act felt sudden and presented new challenges and concerns for oncologists surrounding patients' potential emotional reactions to medical notes or lack of control over the careful delivery of potentially life-changing information. Despite data that show most patients want immediate access to information in their records before it is communicated directly by a health care professional, surveys of oncologists showed trepidation. In this chapter, perspectives from a patient with cancer, an oncologist, and a cancer psychiatrist (in that order) are shared to illuminate the adjustments made in clinician-patient communication amid the era of nearly instantaneous results within the electronic health record.

National consensus recommendations have recently been developed to standardize colorectal tumour localization and documentation during colonoscopy. In this qualitative semi-structured interview study, we identified and contrast the perceived barriers and facilitators to using these new recommendations according to gastroenterologists and surgeons in a large central Canadian city. Interviews were analyzed according to the Consolidated Framework for Implementation Research (CFIR) through directed content analysis. Solutions were categorized using the Expert Recommendations for Implementing Change (ERIC) framework. Eleven gastroenterologists and ten surgeons participated. Both specialty groups felt that the new recommendations were clearly written, adequately addressed current care practice tensions, and offered a relative advantage versus existing practices. The new recommendations appeared appropriately complex, applicable to most participants, and could be trialed and adapted prior to full implementation. Major barriers included a lack of relevant external or internal organizational incentives, non-existing formal feedback processes, and a lack of individual familiarity with the evidence behind some recommendations. With application of the ERIC framework, common barriers could be addressed through accessing new funding, altering incentive structures, changing record systems, educational interventions, identifying champions, promoting adaptability, and employing audit/feedback processes. Future research is needed to test strategies for feasibility and effectiveness.

Annual lung cancer screening (LCS) with low dose CT reduces lung cancer mortality. LCS is underutilized. Black people who smoke tobacco have high risk of lung cancer but are less likely to be screened than are White people. This study reports provider recommendation and patient completion of LCS and colorectal cancer screening (CRCS) among patients by race to assess for utilization of LCS.

In the United States, women with schizophrenia face challenges in receiving gynecologic care, but little is known about how cervical cancer screening rates vary across time or states in a publicly insured population. We hypothesized that women Medicaid beneficiaries with schizophrenia would be less likely to receive cervical cancer screening across the United States compared with a control population, and that women with schizophrenia and other markers of vulnerability would be least likely to receive screening.

Non-communicable chronic diseases (NCDs) have become a major global health concern. They constitute the leading cause of disabilities, increased morbidity, mortality, and socio-economic disasters worldwide. Medical condition-specific digital biomarker (DB) panels have emerged as valuable tools to manage NCDs. DBs refer to the measurable and quantifiable physiological, behavioral, and environmental parameters collected for an individual through innovative digital health technologies, including wearables, smart devices, and medical sensors. By leveraging digital technologies, healthcare providers can gather real-time data and insights, enabling them to deliver more proactive and tailored interventions to individuals at risk and patients diagnosed with NCDs. Continuous monitoring of relevant health parameters through wearable devices or smartphone applications allows patients and clinicians to track the progression of NCDs in real time. With the introduction of digital biomarker monitoring (DBM), a new quality of primary and secondary healthcare is being offered with promising opportunities for health risk assessment and protection against health-to-disease transitions in vulnerable sub-populations. DBM enables healthcare providers to take the most cost-effective targeted preventive measures, to detect disease developments early, and to introduce personalized interventions. Consequently, they benefit the quality of life (QoL) of affected individuals, healthcare economy, and society at large. DBM is instrumental for the paradigm shift from reactive medical services to 3PM approach promoted by the European Association for Predictive, Preventive, and Personalized Medicine (EPMA) involving 3PM experts from 55 countries worldwide. This position manuscript consolidates multi-professional expertise in the area, demonstrating clinically relevant examples and providing the roadmap for implementing 3PM concepts facilitated through DBs.

This study aims to explore the common genetic basis between respiratory diseases and to identify shared molecular and biological mechanisms.

Vaping products are diverse with a wide variety of features, and popular products change rapidly. This study examined the features and types of vaping products that people who smoke and/or vape perceive contribute to the health harms of vaping.

Strong opioids are the cornerstone in the treatment of cancer-related pain.

Senescence is a cellular state linked to ageing and age-onset disease across many mammalian species. Acutely, senescent cells promote wound healing and prevent tumour formation; but they are also pro-inflammatory, thus chronically exacerbate tissue decline. Whereas senescent cells are active targets for anti-ageing therapy, why these cells form in vivo, how they affect tissue ageing and the effect of their elimination remain unclear. Here we identify naturally occurring senescent glia in ageing Drosophila brains and decipher their origin and influence. Using Activator protein 1 (AP1) activity to screen for senescence, we determine that senescent glia can appear in response to neuronal mitochondrial dysfunction. In turn, senescent glia promote lipid accumulation in non-senescent glia; similar effects are seen in senescent human fibroblasts in culture. Targeting AP1 activity in senescent glia mitigates senescence biomarkers, extends fly lifespan and health span, and prevents lipid accumulation. However, these benefits come at the cost of increased oxidative damage in the brain, and neuronal mitochondrial function remains poor. Altogether, our results map the trajectory of naturally occurring senescent glia in vivo and indicate that these cells link key ageing phenomena: mitochondrial dysfunction and lipid accumulation.

Black individuals in the United States (US) have a higher incidence of and mortality from colorectal cancer (CRC) compared to other racial groups, and CRC is the second leading cause of death among Hispanic/Latino populations in the US. Patient navigation is an evidence-based approach to narrow inequities in cancer screening among Black and Hispanic/Latino patients. Despite this, limited healthcare systems have implemented patient navigation for screening at scale.

The main objectives of the current paper were to examine the feasibility, acceptability, and adherence of a remotely delivered intervention consisting of mindfulness-based stress reduction plus prenatal sleep classes (MBSR+PS) compared with treatment as usual (TAU).

Methamphetamine use disorder (MUD) is a chronic, relapsing disease that is characterized by repeated drug use despite negative consequences and for which there are currently no FDA-approved cessation therapeutics. Repeated methamphetamine (METH) use induces long-term gene expression changes in brain regions associated with reward processing and drug-seeking behavior, and recent evidence suggests that methamphetamine-induced neuroinflammation may also shape behavioral and molecular responses to the drug. Microglia, the resident immune cells in the brain, are principal drivers of neuroinflammatory responses and contribute to the pathophysiology of substance use disorders. Here, we investigated transcriptional and morphological changes in dorsal striatal microglia in response to methamphetamine-taking and during methamphetamine abstinence, as well as their functional contribution to drug-taking behavior. We show that methamphetamine self-administration induces transcriptional changes associated with protein folding, mRNA processing, immune signaling, and neurotransmission in dorsal striatal microglia. Importantly, many of these transcriptional changes persist through abstinence, a finding supported by morphological analyses. Functionally, we report that microglial ablation increases methamphetamine-taking, possibly involving neuroimmune and neurotransmitter regulation. In contrast, microglial depletion during abstinence does not alter methamphetamine-seeking. Taken together, these results suggest that methamphetamine induces both short and long-term changes in dorsal striatal microglia that contribute to altered drug-taking behavior and may provide valuable insights into the pathophysiology of MUD.

Prior regional Cerebral Blood Flow (rCBF) studies in Major Depressive Disorder (MDD) have been limited by small, highly selective, non-representative samples that have yielded variable and poorly replicated findings. The aim of this study was to compare rCBF measures in a large, more representative community sample of adults with MDD and healthy control participants. This is a cross-sectional, retrospective multi-site cohort study in which clinical data from 338 patients 18-65 years of age with a primary diagnosis of MDD were retrieved from a central database for 8 privately owned, private-pay outpatient psychiatric centers across the United States. Two Tc-HMPAO SPECT brain scans, one at rest and one during performance of a continuous performance task, were acquired as a routine component of their initial clinical evaluation. In total, 103 healthy controls, 18-65 years old and recruited from the community were also assessed and scanned. Depressed patients had significantly higher rCBF in frontal, anterior cingulate, and association cortices, and in basal ganglia, thalamus, and cerebellum, after accounting for significantly higher overall CBF. Depression severity associated positively with rCBF in the basal ganglia, hippocampus, cerebellum, and posterior white matter. Elevated rCBF was especially prominent in women and older patients. Elevated rCBF likely represents pathogenic hypermetabolism in MDD, with its magnitude in direct proportion to depression severity. It is brain-wide, with disproportionate increases in cortical and subcortical attentional networks. Hypermetabolism may be a reasonable target for novel therapeutics in MDD.

This study aims to investigate the association between fear of cancer recurrence (FCR) and death anxiety (DA) among Chinese cancer patients, while considering the mediating effects of experiential avoidance (EA) and meaning in life (MIL).

Vietnam is experiencing a growing burden of cancer, including among people living with HIV. Stigma acts as a sociocultural barrier to the prevention and treatment of both conditions. This study investigates how cultural notions of "respected personhood" (or "what matters most") influence manifestations of HIV-related stigma and cancer stigma in Hanoi, Vietnam.

In 2017, the U.S. Food and Drug Administration (FDA) announced a regulatory plan to reduce the nicotine content of cigarettes. This study examines the association of exposure to industry-sponsored corrective statements on perceptions of the addictiveness of low-nicotine cigarettes relative to typical cigarettes within the general US population.

Effective communication about cancer diagnosis and prognosis in sub-Saharan African oncology settings is often challenged by the cancer-related shame and stigma patients and families experience. Enhancing empathic communication between health care providers, including physicians and nurses, and oncology patients and their families can not only reduce cancer stigma but also improve patient engagement, treatment satisfaction, and quality of life. To reduce lung cancer stigma, we adapted an evidence-based empathic communication skills training intervention to reduce patients' experience of stigma in Nigeria and conducted a pilot study examining the feasibility and acceptability of the empathic communication skills training. Thirty health care providers, recruited from University College Hospital, Ibadan, and Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife, participated in a 2.25-hour didactic and experiential training session. Participant surveys were completed before and after the training. Overall, participants reported highly favorable training evaluations, with at least 85% of health care providers agreeing or strongly agreeing to survey items assessing training relevance, novelty, clarity, and facilitator effectiveness. Self-efficacy to communicate empathically with patients increased significantly from before-training (Mean [SD] = 3.93 [0.28]) to after-training (Mean [SD] = 4.55 [0.15]; t29 = 3.51, P < .05). Significant improvements were observed in health care provider reports of empathy toward lung cancer survivors and attitude toward lung cancer care as well as significant reductions in lung cancer blame were noted. The empathic communication skills training was feasible, well received by oncology clinicians in Nigeria, and demonstrated improvements in health care provider-reported outcomes from before- to after-training.

Persons with HIV-associated Kaposi's sarcoma (KS) experience three co-existing stigmatizing health conditions: skin disease, HIV, and cancer, which contribute to a complex experience of stigmatization and to delays in diagnosis and treatment. Despite the importance of stigma among these patients, there are few proven stigma-reduction strategies for HIV-associated malignancies. Using qualitative methods, we explore how people with HIV-associated KS in western Kenya between August 2022 and 2023 describe changes in their stigma experience after participation in a multicomponent navigation strategy, which included 1) physical navigation and care coordination, 2) video-based education with motivational survivor stories, 3) travel stipend, 4) health insurance enrollment assistance, 5) health insurance stipend, and 6) peer mentorship. A purposive sample of persons at different stages of chemotherapy treatment were invited to participate. Participants described how a multicomponent navigation strategy contributed to increased knowledge and awareness, a sense of belonging, hope to survive, encouragement, and social support, which served as stigma mitigators, likely counteracting the major drivers of intersectional stigma in HIV-associated KS.

The present study sought to determine the prevalence of chronic non-cancer pain (CNCP) among older adult inpatients with polypharmacy. It also aimed to analyse prescription patterns and assess the therapy adequacy and patient complexity for those with and without CNCP.

To fully explore the potential of F-labeled l-fluoroalanine for imaging cancer and other chronic diseases, a simple and mild radiosynthesis method has been established to produce optically pure l-3-[F]fluoroalanine (l-[F]FAla), using a serine-derivatized, five-membered-ring sulfamidate as the radiofluorination precursor. A deuterated analogue, l-3-[F]fluoroalanine-d (l-[F]FAla-d), was also prepared to improve metabolic stability. Both l-[F]FAla and l-[F]FAla-d were rapidly taken up by 9L/lacZ, MIA PaCa-2, and U87MG cells and were shown to be substrates for the alanine-serine-cysteine (ASC) amino acid transporter. The ability of l-[F]FAla, l-[F]FAla-d, and the d-enantiomer, d-[F]FAla-d, to image tumors was evaluated in U87MG tumor-bearing mice. Despite the significant bone uptake was observed for both l-[F]FAla and l-[F]FAla-d, the latter had enhanced tumor uptake compared to l-[F]FAla, and d-[F]FAla-d was not specifically taken up by the tumors. The enhanced tumor uptake of l-[F]FAla-d compared with its nondeuterated counterpart, l-[F]FAla, warranted the further biological investigation of this radiotracer as a potential cancer imaging agent.

This narrative review examines recent research on end of life (EOL) care for people with dementia and comorbid cancer, highlighting the complexity and challenge of providing effective EOL care for this group and areas of interest for future research.

Normal cells coordinate proliferation and differentiation by precise tuning of gene expression based on the dynamic shifts of the epigenome throughout the developmental timeline. Although non-mutational epigenetic reprogramming is an emerging hallmark of cancer, the epigenomic shifts that occur during the transition from normal to malignant cells remain elusive. Here, we capture the epigenomic changes that occur during tumorigenesis in a prototypic embryonal brain tumor, medulloblastoma. By comparing the epigenomes of the different stages of transforming cells in mice, we identify nuclear factor I family of transcription factors, known to be cell fate determinants in development, as oncogenic regulators in the epigenomes of precancerous and cancerous cells. Furthermore, genetic and pharmacological inhibition of NFIB validated a crucial role of this transcription factor by disrupting the cancer epigenome in medulloblastoma. Thus, this study exemplifies how epigenomic changes contribute to tumorigenesis via non-mutational mechanisms involving developmental transcription factors.

Sleep problems constitute a common and heterogeneous complaint in pediatric palliative care (PPC), where they often contribute to disease morbidity and cause additional distress to children and adolescents and their families already facing the burden of life-threatening and life-limiting conditions. Despite the significant impact of sleep problems, clinical evidence is lacking. The application of general pediatric sleep recommendations appears insufficient to address the unique challenges of the PPC dimension in terms of disease variability, duration, comorbidities, complexity of needs, and particular features of sleep problems related to hospice care. Therefore, we initiated an international project aimed at establishing a multidisciplinary consensus.

Psilocybin-assisted psychotherapy (PAP) is a promising treatment option for depression, with randomized controlled trials (RCTs) providing preliminary support for its safety and efficacy. However, there is a lack of consistency across existing treatment protocols and psychotherapeutic approaches. The objective of this review is to summarize and compare current psychotherapy methods of PAP in treating depression and distress in life-threatening illnesses. We sought to comprehensively summarize published psychotherapy protocols from clinical trials to provide insights for future practices.

This case report delves into the rare occurrence of hyperventilation syndrome (HVS) with hypocalcemia in an 18-year-old female diagnosed with autism spectrum disorder (ASD). The rare occurrence highlights the importance of recognizing the potential association between HVS, hypocalcemia, and ASD, emphasizing the need for comprehensive evaluation and management strategies in individuals with ASD presenting with unusual symptoms. Despite ongoing psychotherapeutic treatment, the patient's clinical examination revealed ASD-related communication anomalies. Treatment with Escitalopram resolved panic attacks but left residual anxiety. During an emergency room visit for menstrual-related abdominal pain, a hyperventilation crisis ensued, leading to respiratory alkalosis and hypocalcemia. Swift intervention, including closed mask ventilation and electrolyte infusion, successfully alleviated symptoms. Follow-up assessments indicated normal thyroid function and vitamin D levels. The case highlights the necessity for clinicians to consider electrolyte imbalances in anxiety attacks among ASD patients, emphasizing the importance of timely management for patient safety. The intricate interplay between hyperventilation syndrome, anxiety, and hypocalcemia in ASD patients is explored, offering valuable insights for the nuanced understanding and comprehensive assessment of such cases.

To examine the psychiatric and physical health burden of obstructive respiratory disease in a nationally representative sample of U.S. Veterans.

Compared to other occupations, physicians are more susceptible to depression and suicide. Suicide among physicians in some countries reached up to 1.5- to threefold higher than the general population. However, this rate was not homogenous in all countries. Most of the Egyptian studies were related to the stressful pandemic event, but the actual prevalence of depression among physicians is still under research. To the best of the researcher's knowledge, no other study has been conducted to evaluate the risk of suicide among Egyptian physicians.

Cigarette smoking accounts for >30% of the socioeconomic gap in life expectancy. Flavored restrictions claim to promote equity; however, no previous studies have compared the effect of cigarette and e-cigarette flavor restrictions among individuals who smoke with lower and higher socioeconomic status (SES).

Prostate cancer is projected to be the most common cancer among people living with HIV; however, incidence of prostate cancer has been reported to be lower in men with HIV compared to men without HIV with little evidence to explain this difference. We describe prostate cancer incidence by HIV status in Medicaid beneficiaries, allowing for comparison of men with and without HIV who are similar with respect to socioeconomic characteristics and access to healthcare.

In their recent Viewpoint article, Beidas et al. (2023) argue that researchers should test psychosocial interventions in the contexts in which they are meant to be delivered and that they can accelerate the deployment of these interventions by advancing directly from pilot trials to effectiveness and implementation studies without conducting efficacy trials. In this commentary, we argue that this is a well-intended but problematic approach and that there is a more productive strategy for translational behavioral intervention research. The commentary discusses issues concerning intervention development, refinement, and optimization; pilot and efficacy testing of interventions; the contexts in which interventions are delivered; clinical practice guidelines; and quick versus programmatic answers to significant clinical research questions. Testing psychosocial interventions in the contexts in which they are meant to be delivered is a complex task for interventions that are designed to be used in a wide variety of contexts. Nevertheless, interventions can be tested in the contexts in which they are meant to be delivered without sacrificing programmatic intervention development or safety and efficacy testing. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Chemotherapy is notorious for causing behavioral side effects (e.g., cognitive decline). Notably, the gut microbiome has recently been reported to communicate with the brain to affect behavior, including cognition. Thus, the aim of this clinical longitudinal observational study was to determine whether chemotherapy-induced disruption of the gut microbial community structure relates to cognitive decline and circulating inflammatory signals. Fecal samples, blood, and cognitive measures were collected from 77 patients with breast cancer before, during, and after chemotherapy. Chemotherapy altered the gut microbiome community structure and increased circulating TNF-α. Both the chemotherapy-induced changes in microbial relative abundance and decreased microbial diversity were related to elevated circulating pro-inflammatory cytokines TNF-α and IL-6. Participants reported subjective cognitive decline during chemotherapy, which was not related to changes in the gut microbiome or inflammatory markers. In contrast, a decrease in overall objective cognition was related to a decrease in microbial diversity, independent of circulating cytokines. Stratification of subjects, via a reliable change index based on 4 objective cognitive tests, identified objective cognitive decline in 35% of the subjects. Based on a differential microbial abundance analysis, those characterized by cognitive decline had unique taxonomic shifts (Faecalibacterium, Bacteroides, Fusicatenibacter, Erysipelotrichaceae UCG-003, and Subdoligranulum) over chemotherapy treatment compared to those without cognitive decline. Taken together, gut microbiome change was associated with cognitive decline during chemotherapy, independent of chemotherapy-induced inflammation. These results suggest that microbiome-related strategies may be useful for predicting and preventing behavioral side effects of chemotherapy.

This study aimed to estimate the population-attributable fraction (PAF) of psychiatric and physical disorders for suicide among older adults, focusing on sex- and age-specific factors.

Paraneoplastic encephalitis (PE) represents a rare but significant complication in patients with testicular cancer (TC). Given the paucity of comprehensive literature on this topic, our review seeks to consolidate current knowledge and provide evidence-based recommendations for the diagnosis, prognosis, and management of PE in the context of TC.

This study aimed to develop a patient-centered survivorship care plan (SCP) for US military Veteran bladder cancer (BC) survivors in accordance with the National Academy of Medicine recommendation that survivors receive an SCP at treatment completion. BC, which differentially impacts older men, is a costly and highly recurrent cancer associated with invasive procedures and long-term surveillance. Veteran BC survivors may face challenges navigating the patient-to-survivor transition due to their age and comorbidities.

Identifying health care utilization and costs associated with active and passive smoking during pregnancy could help improve health management strategies.

Turning Point Analysis (TPA) is a methodological approach that allows scholars to retrospectively capture change over time by identifying instances of critical change (i.e., turning points) encountered across a given time period. While TPA has been used to examine time as a variable in health and illness experiences, the use of the method in behavioral medicine scholarship may be limited by the lack of understanding of TPA procedures and applicability.

We assessed adults' perceived relative harm and addictiveness of products using FDA-authorized modified risk tobacco products (MRTP) claims and associations with intentions to use MRTPs.

Although many symptoms of post-COVID syndrome have been described, a comprehensive evaluation of their prevalence is lacking. We aimed to describe symptoms at 16 months from hospitalization for COVID-19.

The translation of evidence-based interventions into practice settings remains challenging. Implementation science aims to bridge the evidence-to-practice gap by understanding multilevel contexts and tailoring evidence-based interventions accordingly. Engaging community partners who possess timely, local knowledge is crucial for this process to be successful. The Disparities Elimination through Coordinated Interventions to Prevent and Control Heart and Lung Disease Risk (DECIPHeR) Alliance aims to address cardiopulmonary health disparities by engaging diverse community partners to improve the implementation of evidence-based interventions. The goal of the Community Engagement Subcommittee is to strengthen community engagement practice across DECIPHeR. This paper presents the subcommittee's "Why We Engage Communities" statement that outlines why community engagement is critical for implementation science. The paper also provides case examples of DECIPHeR community engagement activities.

Angelman syndrome (AS) is a neurogenetic disorder caused by mutations or deletions in the maternally-inherited allele, leading to a loss of UBE3A protein expression in neurons. The paternally-inherited allele is epigenetically silenced in neurons during development by a noncoding transcript (). The absence of neuronal UBE3A results in severe neurological symptoms, including speech and language impairments, intellectual disability, and seizures. While no cure exists, therapies aiming to restore UBE3A function-either by gene addition or by targeting -are under development. Progress in developing these treatments relies heavily on inferences drawn from mouse studies about the function of UBE3A in the human brain. To aid translational efforts and to gain an understanding of UBE3A and biology with greater relevance to human neurodevelopmental contexts, we investigated UBE3A and expression in the developing brain of the rhesus macaque, a species that exhibits complex social behaviors, resembling aspects of human behavior to a greater degree than mice. Combining immunohistochemistry and hybridization, we mapped UBE3A and regional and cellular expression in normal prenatal, neonatal, and adolescent rhesus macaque brains. We show that key hallmarks of UBE3A biology, well-known in rodents, are also present in macaques, and suggest paternal silencing in neurons-but not glial cells-in the macaque brain, with onset between gestational day 48 and 100. These findings support proposals that early-life, perhaps even prenatal, intervention is optimal for overcoming the maternal allele loss of linked to AS.

Intrinsic, expansile pontine tumors typically occur in the pediatric population. These tumors characteristically present as diffuse intrinsic pontine glioma (DIPG), which is now considered as diffuse midline glioma (DMG), H3K27-mutated of the pons. DIPG has limited treatment options and a poor prognosis, and the value of tissue diagnosis from an invasive biopsy remains controversial. This study presents the case of a 19-year-old female with clinical and imaging hallmarks of DIPG, who underwent a biopsy of a tumor in the region of the right middle cerebellar peduncle. Her lesional cells were negative for H3K27M alterations and had low-grade histologic features. Next-generation sequencing revealed a frameshift mutation in the gene as the likely driver mutation. These features suggest a diagnosis of a low-grade glioma associated with loss of function, with far-reaching consequences regarding both treatment strategy and prognosis. This case provides support for the utility of diagnostic tissue biopsy in cases of suspected DIPG.

Protein kinase C (PKC) plays a key role in modulating the activities of the innate immune cells of the central nervous system (CNS). A delicate balance between pro-inflammatory and regenerative activities by microglia and CNS-associated macrophages is necessary for the proper functioning of the CNS. Thus, a maladaptive activation of these CNS innate immune cells results in neurodegeneration and demyelination associated with various neurologic disorders, such as multiple sclerosis (MS) and Alzheimer's disease. Prior studies have demonstrated that modulation of PKC activity by bryostatin-1 (bryo-1) and its analogs (bryologs) attenuates the pro-inflammatory processes by microglia/CNS macrophages and alleviates the neurologic symptoms in experimental autoimmune encephalomyelitis (EAE), an MS animal model. Here, we demonstrate that (2S,5S)-(E,E)-8-(5-(4-(trifluoromethyl)phenyl)-2,4-pentadienoylamino)benzolactam (TPPB), a structurally distinct PKC modulator, has a similar effect to bryo-1 on CNS innate immune cells both and , attenuating neuroinflammation and resulting in CNS regeneration and repair. This study identifies a new structural class of PKC modulators, which can therapeutically target CNS innate immunity as a strategy to treat neuroinflammatory and neurodegenerative disorders.

Family health history (FHx) is an important tool in assessing one's risk towards specific health conditions. However, user experience of FHx collection tools is rarely studied. ItRunsInMyFamily.com (ItRuns) was developed to assess FHx and hereditary cancer risk. This study reports a quantitative user experience analysis of ItRuns.

Insomnia is one of the most common symptoms among breast cancer patients, which can be present throughout all stages of breast cancer. As a non-pharmacological alternative treatment, acupuncture has been suggested to improve sleep situations in patients with cancer suffering from insomnia. However, there is a lack of well-designed, high-quality clinical evidence regarding the efficacy of acupuncture in the treatment of breast cancer-related insomnia. This study is conducted to evaluate the efficacy and safety of acupuncture treatment for breast cancer-related insomnia.

PREVENT is a multi-centre prospective cohort study in the UK and Ireland that aims to examine midlife risk factors for dementia and identify and describe the earliest indices of disease development. The PREVENT dementia programme is one of the original epidemiological initiatives targeting midlife as a critical window for intervention in neurodegenerative conditions. This paper provides an overview of the study protocol and presents the first summary results from the initial baseline data to describe the cohort. Participants in the PREVENT cohort provide demographic data, biological samples (blood, saliva, urine and optional cerebrospinal fluid), lifestyle and psychological questionnaires, undergo a comprehensive cognitive test battery and are imaged using multi-modal 3-T MRI scanning, with both structural and functional sequences. The PREVENT cohort governance structure is described, which includes a steering committee, a scientific advisory board and core patient and public involvement groups. A number of sub-studies that supplement the main PREVENT cohort are also described. The PREVENT cohort baseline data include 700 participants recruited between 2014 and 2020 across five sites in the UK and Ireland (Cambridge, Dublin, Edinburgh, London and Oxford). At baseline, participants had a mean age of 51.2 years (range 40-59, SD ± 5.47), with the majority female ( = 433, 61.9%). There was a near equal distribution of participants with and without a parental history of dementia (51.4% versus 48.6%) and a relatively high prevalence of APOEɛ4 carriers ( = 264, 38.0%). Participants were highly educated (16.7 ± 3.44 years of education), were mainly of European Ancestry ( = 672, 95.9%) and were cognitively healthy as measured by the Addenbrookes Cognitive Examination-III (total score 95.6 ± 4.06). Mean white matter hyperintensity volume at recruitment was 2.26 ± 2.77 ml (median = 1.39 ml), with hippocampal volume being 8.15 ± 0.79 ml. There was good representation of known dementia risk factors in the cohort. The PREVENT cohort offers a novel data set to explore midlife risk factors and early signs of neurodegenerative disease. Data are available open access at no cost via the Alzheimer's Disease Data Initiative platform and Dementia Platforms UK platform pending approval of the data access request from the PREVENT steering group committee.

Primary brain neoplasms are associated with elevated mortality and morbidity rates. Brain tumour surgery aims to achieve maximal tumour resection while minimizing damage to healthy brain tissue. Research on Neuromodulation Induced Cortical Prehabilitation (NICP) has highlighted the potential, before neurosurgery, of establishing new brain connections and transfer functional activity from one area of the brain to another. Nonetheless, the neural mechanisms underlying these processes, particularly in the context of space-occupying lesions, remain unclear. A patient with a left frontotemporoinsular tumour underwent a prehabilitation protocol providing 20 sessions of inhibitory non-invasive neuromodulation (rTMS and multichannel tDCS) over a language network coupled with intensive task training. Prehabilitation resulted in an increment of the distance between the tumour and the language network. Furthermore, enhanced functional connectivity within the language circuit was observed. The present innovative case-study exposed that inhibition of the functional network area surrounding the space-occupying lesion promotes a plastic change in the network's spatial organization, presumably through the establishment of novel functional pathways away from the lesion's site. While these outcomes are promising, prudence dictates the need for larger studies to confirm and generalize these findings.

The coronavirus disease (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has detrimental effects on physical and mental health. Patients with severe mental illness are at higher risk of contracting the virus due to social determinants of health. Vulnerable populations include the elderly, people with pre-existing conditions, and those exposed to SARS-CoV-2. Unfortunately, only a few countries have updated vaccination strategies to prioritize patients with mental illnesses. Therefore, we aimed to explore whether individuals with mental disorders are prioritized in vaccine allocation strategies in different world regions. They are often neglected in policymaking but are highly vulnerable to the threatening complications of COVID-19.

The e-cigarette market is large and diverse. Traditional smoking cessation trials involving a control group and a 6-month observation period are an inefficient methodology for testing the multiple treatment options e-cigarettes provide for harm reduction in cigarette smokers. We determined when product substitution occurred in the e-cigarette provision arm of an e-cigarette substitution trial for cigarette smokers who were not interested in quitting.

Highly active antiretroviral therapy (HAART) helps improve some measures of accelerated epigenetic aging in persons living with HIV (PLWH), but its overall impact on the epigenome is not fully understood. In this study, we analyzed the DNA methylation profiles of PLWH ( = 187) shortly before and approximately 2-3 years after they started HAART, as well as matched seronegative (SN) controls ( = 187), taken at two time intervals. Our aim was to identify specific CpGs and biologic pathways associated with HIV infection and initiation of HAART. Additionally, we attempted to identify epigenetic changes associated with HAART initiation that were independent of HIV-associated changes, using matched HIV seronegative (SN) controls (matched on age, hepatitis C status, and interval between visits) to identify CpGs that did not differ between PLWH and SN pre-HAART but were significantly associated with HAART initiation while being unrelated to HIV viral load. Epigenome-wide association studies (EWAS) on >850,000 CpG sites were performed using pre- and post-HAART samples from PLWH. The results were then annotated using the Genomic Regions Enrichment of Annotations Tool (GREAT). When only pre- and post-HAART visits in PLWH were compared, gene ontologies related to immune function and diseases related to immune function were significant, though with less significance for PLWH with detectable HIV viral loads (>50 copies/mL) at the post-HAART visit. To specifically elucidate the effects of HAART separately from HIV-induced methylation changes, we performed EWAS of HAART while also controlling for HIV viral load, and found gene ontologies associated with transplant rejection, transplant-related diseases, and other immunologic signatures. Additionally, we performed a more focused analysis that examined CpGs reaching genome-wide significance ( < 1 × 10) from the viral load-controlled EWAS that did not differ between all PLWH and matched SN controls pre-HAART. These CpGs were found to be near genes that play a role in retroviral drug metabolism, diffuse large B cell lymphoma proliferation, and gastric cancer metastasis. Overall, this study provides insight into potential biological functions associated with DNA methylation changes induced by HAART initiation in persons living with HIV.

Autophagy mediates the degradation of intracellular macromolecules and organelles within lysosomes. There are three types of autophagy: macroautophagy, microautophagy, and chaperone-mediated autophagy. Heat shock protein 70.1 (Hsp70.1) exhibits dual functions as a chaperone protein and a lysosomal membrane stabilizer. Since chaperone-mediated autophagy participates in the recycling of ∼30% cytosolic proteins, its disorder causes cell susceptibility to stress conditions. Cargo proteins destined for degradation such as amyloid precursor protein and tau protein are trafficked by Hsp70.1 from the cytosol into lysosomes. Hsp70.1 is composed of an N-terminal nucleotide-binding domain (NBD) and a C-terminal domain that binds to cargo proteins, termed the substrate-binding domain (SBD). The NBD and SBD are connected by the interdomain linker L, which modulates the allosteric structure of Hsp70.1 in response to ADP/ATP binding. After the passage of the Hsp70.1-cargo complex through the lysosomal limiting membrane, high-affinity binding of the positive-charged SBD with negative-charged bis(monoacylglycero)phosphate (BMP) at the internal vesicular membranes activates acid sphingomyelinase to generate ceramide for stabilizing lysosomal membranes. As the integrity of the lysosomal limiting membrane is critical to ensure cargo protein degradation within the acidic lumen, the disintegration of the lysosomal limiting membrane is lethal to cells. After the intake of high-fat diets, however, β-oxidation of fatty acids in the mitochondria generates reactive oxygen species, which enhance the oxidation of membrane linoleic acids to produce 4-hydroxy-2-nonenal (4-HNE). In addition, 4-HNE is produced during the heating of linoleic acid-rich vegetable oils and incorporated into the body via deep-fried foods. This endogenous and exogenous 4-HNE synergically causes an increase in its serum and organ levels to induce carbonylation of Hsp70.1 at Arg469, which facilitates its conformational change and access of activated μ-calpain to L. Therefore, the cleavage of Hsp70.1 occurs prior to its influx into the lysosomal lumen, which leads to lysosomal membrane permeabilization/rupture. The resultant leakage of cathepsins is responsible for lysosomal cell death, which would be one of the causative factors of lifestyle-related diseases.

Of all psychiatric disorders, schizophrenia is associated with the highest risk of all-cause mortality. This study aimed to investigate independent risk factors for all-cause mortality in patients with chronic schizophrenia. In addition, the possible causal inter-relationships among these independent risk factors and all-cause mortality were also explored.