The relationship of race, ethnicity, gender identity, sex assigned at birth, sexual orientation, parental education, financial hardship and comorbid mental disorders with quality of life in college students with anxiety, depression or eating disorders.

BACKGROUND: Previous studies showed that comorbidity and demographic factors added to burden on health-related quality of life (HRQoL). Only one study explored the relationship between HRQoL and comorbidity in college students with mental disorders, leaving generalizability of findings uncertain. Less is known about the association of demographics on HRQoL. This study investigated HRQoL based on demographics and comorbidity among college students with mental disorders. METHODS: Participants were students (N = 5535) across 26 U.S. colleges and universities who met criteria for depression, generalized anxiety, panic, social anxiety, post-traumatic stress, or eating disorders based on self-report measures. ANOVA and linear regressions were conducted. RESULTS: Overall, female, minoritized (gender, sexual orientation, race, or ethnicity), and lower socioeconomic status students reported lower HRQoL than male, heterosexual, White, non-Hispanic, and higher socioeconomic status peers. After accounting for comorbidity, differences in physical HRQoL based on sex assigned at birth and gender were no longer significant. For mental HRQoL, only gender and sexual orientation remained significant. A greater number of comorbidities was associated with lower HRQoL regardless of demographic group. LIMITATIONS: The non-experimental design limits causal inference. The study focused on univariable associations without examining potential interactions between demographic factors. Future research should explore structural factors like discrimination. CONCLUSION: Results suggested that increased comorbidities placed an additional burden on HRQoL and that certain demographic groups were more vulnerable to HRQoL impairment among students with mental disorders. Findings suggest the need for prevention of disorders and their comorbidity and implementing tailored interventions for specific student subgroups with increased vulnerability.

FAP Radioligand Linker Optimization Improves Tumor Dose and Tumor-to-Healthy Organ Ratios in 4T1 Syngeneic Model.

Fibroblast activation protein (FAP) has attracted considerable attention as a possible target for the radiotherapy of solid tumors. Unfortunately, initial efforts to treat solid tumors with FAP-targeted radionuclides have yielded only modest clinical responses, suggesting that further improvements in the molecular design of FAP-targeted radiopharmaceutical therapies (RPT) are warranted. In this study, we report several advances on the previously described FAP6 radioligand that increase tumor retention and accelerate healthy tissue clearance. Seven FAP6 derivatives with different linkers or albumin binders were synthesized, radiolabeled, and investigated for their effects on binding and cellular uptake. The radioligands were then characterized in 4T1 tumor-bearing Balb/c mice using both single-photon emission computed tomography (SPECT) and ex vivo biodistribution analyses to identify the conjugate with the best tumor retention and tumor-to-healthy organ ratios. The results reveal an optimized FAP6 radioligand that exhibits efficacy and safety properties that potentially justify its translation into the clinic.

Dietary Flavonoid and Subclass Intakes are not Associated with Markers of Bone Health in U.S. Adults Age 50+ Years.

BACKGROUND: Dietary flavonoid intakes have been associated with improved markers of bone health in Chinese and Scottish cohorts, but little data exist in middle aged to older adults in the United States. OBJECTIVES: The objective of our research was to assess if dietary flavonoid intakes are associated with bone mineral density (BMD), bone mineral content (BMC), and bone area of the lumbar spine and femoral neck in a nationally representative population of middle aged to older U.S. adults. We further sought to investigate if relationships of the main flavonoid subgroups (i.e., anthocyanins, flavan-3-ols, flavanones, flavones, flavonols, and isoflavones) exist, as a secondary objective. METHODS: Cross-sectional data from individuals aged 50+ years enrolled in the 2017-2018 National Health and Nutrition Examination Survey (NHANES) were used in our analyses (N = 2590). Weighted multivariate logistic regression models were used to investigate the relationship between quartiles of flavonoid intake and BMD, BMC, and bone area of the lumbar spine and femoral neck of participants. RESULTS: Mean age of participants was 63.4 ± 0.52 years and 64.1 ± 0.52 years for men and women, respectively. Average total flavonoid intake was 217 ± 19.4 mg/day and 306 ± 26.9 mg/day for men and women, respectively. Total flavonoid intakes were not significantly associated with BMD, BMC, or bone area of the femoral neck or lumbar spine in male or female participants. Flavonoid subclass intakes were also not consistently associated with improved markers of bone health. CONCLUSION: Although several limitations exist, this cross-sectional analysis of U.S. adults aged 50+ years provides contradictory evidence to the hypothesis that higher flavonoid and flavonoid subclass intakes beneficially impacts markers of bone health. Large prospective cohort investigations that better capture long-term dietary flavonoid intake and ascertain fractures the primary outcome, as well as randomized controlled trials, are needed to fully elucidate the effects flavonoids on bone health.

Overexpression of human DNA polymerase theta is a biomarker of aggressive and DNA repair-deficient papillary thyroid cancers.

BACKGROUND: DNA polymerase theta (POLQ) is an enzyme that repairs double-strand DNA breaks. POLQ is overexpressed in several cancer types, and increased expression is associated with a poor prognosis. Ablating POLQ function in vitro increases drug sensitivity to agents that cause double-strand DNA breaks, including chemotherapies and ionizing radiation. POLQ's role in thyroid cancer remains poorly understood. METHODS: Expression of POLQ and other genes of interest were analyzed in 513 papillary thyroid cancers (505 primary tumors and 8 metastatic lesions) and 59 normal thyroid samples available in the Cancer Genome Atlas. The Cancer Genome Atlas RNA and DNA sequencing data were queried with the Xena platform. The Recombination Proficiency Score was calculated to assess DNA repair efficiency. Other signaling events associated with thyroid tumorigenesis and clinical outcomes were analyzed. Univariate and multivariate analyses were performed. Treatment with the POLQ inhibitors ART558 and Novobiocin tested the effect of POLQ inhibition on in vitro thyroid cancer growth. RESULTS: POLQ expression was increased in papillary thyroid cancers compared to normal thyroid tissue (P < .05). POLQ expression levels were inversely correlated with Recombination Proficiency Score levels (P < .05). POLQ expression was highest in tall cell papillary thyroid cancers and in metastases. Higher POLQ expression was also associated with dedifferentiation, BRAF signaling, and shorter progression-free intervals (P < .05). Treatment with POLQ inhibitors decreased in vitro thyroid cancer growth (P < .05). CONCLUSION: These findings suggest that increased POLQ expression could serve as a valuable clinical marker and a potential therapeutic target in the treatment of thyroid cancer.

Evaluation and Surgical Management of Multiple Endocrine Neoplasias.

Multiple endocrine neoplasia (MEN) syndromes are rare autosomal dominant diseases that are associated with a mixture of both endocrine and non-endocrine tumors. Traditionally, there are 2 types of MEN that have unique clinical associations: MEN 1 (parathyroid hyperplasia, pancreatic neuroendocrine tumors, and pituitary tumors) and MEN 2 (medullary thyroid carcinoma and pheochromocytoma), which is further classified into MEN 2A (adds parathyroid adenomas) and 2B (adds ganglioneuromas and marfanoid habitus). Many of the endocrine tumors are resected surgically, and the pre, intra, and postoperative management strategies used must take into account the high recurrence rates asscioated with MEN tumors.

Estimated Doses to the Heart, Lungs and Oesophagus and Risks From Typical UK Radiotherapy for Early Breast Cancer During 2015-2023.

PURPOSE: Breast cancer radiotherapy can increase the risks of heart disease, lung cancer and oesophageal cancer. At present, the best dosimetric predictors of these risks are mean doses to the whole heart, lungs and oesophagus, respectively. We aimed to estimate typical doses to these organs and resulting risks from UK breast cancer radiotherapy. METHODS: A systematic review and meta-analysis was conducted of planned or delivered mean doses to the whole heart, lungs or oesophagus from UK breast cancer radiotherapy in studies published during 2015-2023. Average mean doses were summarised for combinations of laterality and clinical targets. Heart disease and lung cancer mortality risks were then estimated using established models. RESULTS: For whole heart, thirteen studies reported 2893 doses. Average mean doses were higher in left than in right-sided radiotherapy and increased with extent of clinical targets. For left-sided radiotherapy, average mean heart doses were: 2.0 Gy (range 1.2-8.0 Gy) breast/chest wall, 2.7 Gy (range 0.6-5.6 Gy) breast/chest wall with either axilla or supraclavicular nodes and 2.9 Gy (range 1.3-4.7 Gy) breast/chest wall with nodes including internal mammary. For right-sided radiotherapy, average mean heart doses were: 1.0 Gy (range 0.3-1.0 Gy) breast/chest wall and 1.2 Gy (range 1.0-1.4 Gy) breast/chest wall with either axilla or supraclavicular nodes. There were no whole heart dose estimates from right internal mammary radiotherapy. For whole lung, six studies reported 2230 doses. Average mean lung doses increased with extent of targets irradiated: 2.6 Gy (range 1.4-3.0 Gy) breast/chest wall, 3.0 Gy (range 0.9-5.1 Gy) breast/chest wall with either axilla or supraclavicular nodes and 7.1 Gy (range 6.7-10.0 Gy) breast/chest wall with nodes including internal mammary. For whole oesophagus, two studies reported 76 doses. Average mean oesophagus doses increased with extent of targets irradiated: 1.4 Gy (range 1.0-2.0 Gy) breast/chest wall with either axilla or supraclavicular nodes and 5.8 Gy (range 1.9-10.0 Gy) breast/chest wall with nodes including internal mammary. CONCLUSIONS: The typical doses to these organs may be combined with dose-response relationships to estimate radiation risks. Estimated 30-year absolute lung cancer mortality risks from modern UK breast cancer radiotherapy for patients irradiated when aged 50 years were 2-6% for long-term continuing smokers, and <1% for non-smokers. Estimated 30-year mortality risks for heart disease were <1%.

Rates and correlates of study enrolment and use of a chatbot aimed to promote mental health services use for eating disorders following online screening.

OBJECTIVE: We developed a chatbot aimed to facilitate mental health services use for eating disorders (EDs) and offered the opportunity to enrol in a research study and use the chatbot to all adult respondents to a publicly available online ED screen who screened positive for clinical/subclinical EDs and reported not currently being in treatment. We examined the rates and correlates of enrolment in the study and uptake of the chatbot. METHOD: Following screening, eligible respondents (≥18 years, screened positive for a clinical/subclinical ED, not in treatment for an ED) were shown the study opportunity. Chi-square tests and logistic regressions explored differences in demographics, ED symptoms, suicidality, weight, and probable ED diagnoses between those who enroled and engaged with the chatbot versus those who did not. RESULTS: 6747 respondents were shown the opportunity (80.0% of all adult screens). 3.0% enroled, of whom 90.2% subsequently used the chatbot. Enrolment and chatbot uptake were more common among respondents aged ≥25 years old versus those aged 18-24 and less common among respondents who reported engaging in regular dietary restriction. CONCLUSIONS: Overall enrolment was low, yet uptake was high among those that enroled and did not differ across most demographics and symptom presentations. Future directions include evaluating respondents' attitudes towards treatment-promoting tools and removing barriers to uptake.

Cost-Effectiveness of Parathyroid Cryopreservation and Autotransplantation.

Importance: Delayed autotransplantation of cryopreserved parathyroid tissue (DACP) is the only surgical treatment for permanent postoperative hypoparathyroidism. Studies suggest that only a small minority of cryopreserved samples are ultimately autotransplanted with highly variable outcomes. For these reasons, many have questioned the economic utility of the process, although, to the authors' knowledge, this has never been formally studied. Objective: To report the clinical outcomes of parathyroid cryopreservation and DACP at a large academic institution and to determine the cost-effectiveness of this treatment. Design, Setting, and Participants: An institutional review board-approved, retrospective review of patients at a single institution who underwent DACP over a 17-year period was conducted with a median follow-up of 48.2 months. A forward-looking cost-utility analysis was then performed to determine the economic utility of cryopreservation/DACP vs usual care (monitoring and supplementation). Patients who had parathyroid tissue in cryopreserved storage between August 2005 to September 2022 at a single-center, academic, quaternary care center were identified. Exposure: Parathyroid cryopreservation and DACP. Main Outcomes and Measures: Graft functionality, clinical outcomes, and cost utility using a willingness-to-pay threshold of $100 000 per quality-adjusted life-year (QALY). Results: A total of 591 patients underwent cryopreservation. Of these, 10 patients (1.7%; mean [SD] age, 45.6 [17.9] years; 6 male [60%]) underwent DACP. A minority of autografts (2 [20%]) were subsequently fully functional, one-half (5 [50%]) were partially functional, and 3 (30%) were not functional. The cost-utility model estimated that at a large academic center over 10 years, the additional cost of 591 patients undergoing cryopreservation and 10 patients undergoing autotransplantation would be $618 791.64 (2022 dollars) and would add 8.75 QALYs, resulting in a cost per marginal QALY of $70 719.04, which is less than the common willingness-to-pay threshold of $100 000/QALY. Conclusions and Relevance: The reimplantation rate of cryopreserved tissue was low (<2%), but when implanted, autografts were at least partially functional 70% of the time. In the first-ever, to the authors' knowledge, formal cost analysis for this treatment, results of the current model suggest that cryopreservation and autotransplantation were cost-effective compared with the usual care for hypoparathyroidism at a large, academic institution. It is recommended that each surgical center consider whether the economic and logistical commitments necessary for cryopreservation are worthwhile for their individual needs.

Dietary Supplement Use in Transmasculine People: Results of an Online Survey of Volunteer Adults.

INTRODUCTION: Health inequities and disparities in nutrition research exist among transmasculine people. A dearth of evidence on dietary supplement use and motivations exist, partially due to constrained collection of sex and gender identity in national surveys. OBJECTIVE: We sought to investigate common motivations and use of dietary supplements in a voluntary survey of transmasculine people. METHODS: A total of 48 participants completed an online survey detailing dietary supplement use, motivations, and demographic information. RESULTS: 64.5 and 90.0% of participants reported use of 1+ dietary supplement within the past 30-days and during some point in their lifetime, respectively. Top reported product types used included multivitamins (52%), melatonin (52%), vitamin D (46%), vitamin C (35%), fish oil (33%), B-vitamins or B-complex (31%), iron (29%), green tea (29%), biotin (25%), cranberry (23%), zinc (23%), protein powder (23%), probiotics (23%), and calcium (21%). There was no relationship between the number of supplements reported and participant age, BMI, income, or mastectomy status (p > 0.05). Participants reported top motivations being for "improving my overall health" (60.4%), "maintaining health" (54.2%), to "supplement my diet due to not getting enough from food"(41.7%), "mental health" (39.6%), and to "prevent colds, boost immune system" (33.3%). CONCLUSION: Transmasculine people in our study reported a high use of dietary supplements. Differences in the types of products and number of products used, as well as specific motivations for use likely exist within this subpopulation, however, future nationally-representative longitudinal studies are needed to fully elucidate these patterns and for informing evidence-based nutrition guidance.

Peri-operative cardiac arrest: epidemiology and clinical features of patients analysed in the 7th National Audit Project of the Royal College of Anaesthetists.

The 7th National Audit Project of the Royal College of Anaesthetists studied peri-operative cardiac arrest in the UK, a topic of importance to patients, anaesthetists and surgeons. Here we report the results of the 12-month registry, from 16 June 2021 to 15 June 2022, focusing on epidemiology and clinical features. We reviewed 881 cases of peri-operative cardiac arrest, giving an incidence of 3 in 10,000 anaesthetics (95%CI 3.0-3.5 per 10,000). Incidence varied with patient and surgical factors. Compared with denominator survey activity, patients with cardiac arrest: included more males (56% vs. 42%); were older (median (IQR) age 60.5 (40.5-80.5) vs. 50.5 (30.5-70.5) y), although the age distribution was bimodal, with infants and patients aged > 66 y overrepresented; and were notably more comorbid (73% ASA physical status 3-5 vs. 27% ASA physical status 1-2). The surgical case-mix included more weekend (14% vs. 11%), out-of-hours (19% vs. 10%), non-elective (65% vs. 30%) and major/complex cases (60% vs. 28%). Cardiac arrest was most prevalent in orthopaedic trauma (12%), lower gastrointestinal surgery (10%), cardiac surgery (9%), vascular surgery (8%) and interventional cardiology (6%). Specialities with the highest proportion of cases relative to denominator activity were: cardiac surgery (9% vs. 1%); cardiology (8% vs. 1%); and vascular surgery (8% vs. 2%). The most common causes of cardiac arrest were: major haemorrhage (17%); bradyarrhythmia (9%); and cardiac ischaemia (7%). Patient factors were judged a key cause of cardiac arrest in 82% of cases, anaesthesia in 40% and surgery in 35%.

The incidence of potentially serious complications during non-obstetric anaesthetic practice in the United Kingdom: an analysis from the 7th National Audit Project (NAP7) activity survey.

Complications and critical incidents arising during anaesthesia due to patient, surgical or anaesthetic factors, may cause harm themselves or progress to more severe events, including cardiac arrest or death. As part of the 7th National Audit Project of the Royal College of Anaesthetists, we studied a prospective national cohort of unselected patients. Anaesthetists recorded anonymous details of all cases undertaken over 4 days at their site through an online survey. Of 416 hospital sites invited to participate, 352 (85%) completed the survey. Among 24,172 cases, 1922 discrete potentially serious complications were reported during 1337 (6%) cases. Obstetric cases had a high reported major haemorrhage rate and were excluded from further analysis. Of 20,996 non-obstetric cases, 1705 complications were reported during 1150 (5%) cases. Circulatory events accounted for most complications (616, 36%), followed by airway (418, 25%), metabolic (264, 15%), breathing (259, 15%), and neurological (41, 2%) events. A single complication was reported in 851 (4%) cases, two complications in 166 (1%) cases and three or more complications in 133 (1%) cases. In non-obstetric elective surgery, all complications were 'uncommon' (10-100 per 10,000 cases). Emergency (urgent and immediate priority) surgery accounted for 3454 (16%) of non-obstetric cases but 714 (42%) of complications with severe hypotension, major haemorrhage, severe arrhythmias, septic shock, significant acidosis and electrolyte disturbances all being 'common' (100-1000 per 10,000 cases). Based on univariate analysis, complications were associated with: younger age; higher ASA physical status; male sex; increased frailty; urgency and extent of surgery; day of the week; and time of day. These data represent the rates of potentially serious complications during routine anaesthesia care and may be valuable for risk assessment and patient consent.

The Relationship of Circulating Choline and Choline-Related Metabolite Levels with Health Outcomes: A Scoping Review of Genome-Wide Association Studies and Mendelian Randomization Studies.

Choline is essential for proper liver, muscle, brain, lipid metabolism, cellular membrane composition, and repair. Understanding genetic determinants of circulating choline metabolites can help identify new determinants of choline metabolism, requirements, and their link to disease endpoints. We conducted a scoping review to identify studies assessing the association of genetic polymorphisms on circulating choline and choline-related metabolite concentrations and subsequent associations with health outcomes. This study follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement scoping review extension. Literature was searched to September 28, 2022, in 4 databases: Embase, MEDLINE, Web of Science, and the Biological Science Index. Studies of any duration in humans were considered. Any genome-wide association study (GWAS) investigating genetic variant associations with circulating choline and/or choline-related metabolites and any Mendelian randomization (MR) study investigating the association of genetically predicted circulating choline and/or choline-related metabolites with any health outcome were considered. Qualitative evidence is presented in summary tables. From 1248 total reviewed articles, 53 were included (GWAS = 27; MR = 26). Forty-two circulating choline-related metabolites were tested in association with genetic variants in GWAS studies, primarily trimethylamine N-oxide, betaine, sphingomyelins, lysophosphatidylcholines, and phosphatidylcholines. MR studies investigated associations between 52 total unique choline metabolites and 66 unique health outcomes. Of these, 47 significant associations were reported between 16 metabolites (primarily choline, lysophosphatidylcholines, phosphatidylcholines, betaine, and sphingomyelins) and 27 health outcomes including cancer, cardiovascular, metabolic, bone, and brain-related outcomes. Some articles reported significant associations between multiple choline types and the same health outcome. Genetically predicted circulating choline and choline-related metabolite concentrations are associated with a wide variety of health outcomes. Further research is needed to assess how genetic variability influences choline metabolism and whether individuals with lower genetically predicted circulating choline and choline-related metabolite concentrations would benefit from a dietary intervention or supplementation.

Decreasing exposure to thyroid radiation in an orthopaedic theatre setting: an educational intervention.

The use of personal protective equipment (PPE) can significantly reduce staff exposure to harmful radiation and infection. Fluoroscopic procedures in orthopaedic theatre can generate high levels of radiation and good adherence to PPE use is essential to reduce long term cancer risk, including thyroid cancer. To assess baseline compliance with PPE, availability of PPE in theatre and carry out an intervention to promote greater use of PPE. This was a closed-loop interventional study set in a level 1 trauma centre and an elective/rehabilitation unit. Data were collected in 40 cases pre and post-intervention from 26th May-7th July 2017. All health care practitioners present at fluoroscopic screening were observed. PPE availability was audited daily. A questionnaire was used to assess surgical and nursing knowledge/practices regarding radiation/infection safety. An educational presentation was delivered to the groups at highest risk of exposure. 39/41 questionnaires were completed (29 surgeons, 10 nurses). 41% of respondents had taken a radiation training course or felt they had adequate training. There was a significant increase in the use of thyroid guards by surgeons 13/115 (11.3%) pre-intervention to 54/117 (46.2%) post-intervention (p<0.001) and radiographers (p=0.019) post-intervention. Logistic regression showed an 89.7% increased likelihood of thyroid guard use post-intervention and a 12.7% increased chance of thyroid guard use for each extra guard available. A short educational, easily replicated session, significantly improved compliance with thyroid guards by orthopaedic surgeons.

A DNA pooling based system to detect Escherichia coli virulence factors in fecal and wastewater samples

The availability of a useful tool for simple and timely detection of the most important virulent varieties of Escherichia coli is indispensable. To this end, bacterial DNA pools which had previously been categorized were obtained from isolated colonies as well as selected in terms of utilized phenotype; the pools were assessed by two PCR Multiplex for the detection of virulent E. coli eaeA, bfpA, stx1, stx2, ipaH, ST, LT, and aatA genes, with the 16S gene used as DNA control. The system was validated with 66 fecal samples and 44 wastewater samples. At least one positive isolate was detected by a virulent gene among the 20 that were screened. The analysis of fecal samples from children younger than 6 years of age detected frequencies of 25% LT positive strains, 8.3% eae, 8.3% bfpA, 16.7% ipaH, as well as 12.5 % aatA and ST. On the other hand, wastewater samples revealed frequencies of 25.7% eaeA positive, 30.3% stx1, 15.1% LT and 19.7% aatA. This study is an initial step toward carrying out epidemiological field research that will reveal the presence of these bacterial varieties.

Actividad del virus de la encefalitis equina venezolana en el norte de Colombia, abril y mayo de 1983 / Venezuelan equine encephalitis virus activity in northern Colombia during April and May 1983

Venezuelan equine encephaltis (VEE) virus was isolated from sentinel hamsters exposed in the Rio de Oro region of Colombia, in the Lake Maracaibo drainage área near the border with Venezuela, in 1983-13 years after the first strain was isolated from the region near Tibu. Hydroxylapatite elution profiles of three isolates from the Rio de Oro region were typical of enzootic strains. Relative abundance data and past isolations suggest that culex (Melanoconion) pedroi is a probable enxootic vector at this focus. The virus was no isolated from forests near Santa Marta and Magangue in the Rio Magdalena drainage área in 1983-9 and 16 years, respectively, after the last previous isolations in those áreas. However, equine animals 2 to 10 years of age and humans 25 to 67 years of age living near the Magangue field study área were positive for VEE virus-specific neutralizing antibodies