Low Calf Circumference is Associated with Prolonged Hospital Stay in Older Patients with Solid Tumors: A Secondary Analysis of a Cohort Study.

BACKGROUND: Older patients with cancer present intense loss of muscle mass (MM). Calf circumference (CC) is a simple measurement that assesses MM. This study analyzed the accuracy and association between low CC and negative outcomes in older patients with solid tumors. METHODS: A secondary analysis of a prospective cohort study of inpatients with cancer was conducted. Low CC was defined as CC ≤34 cm in males and ≤33 cm in females. The CC was adjusted for body mass index by reducing 3 or 7 cm for BMI (in kg/m2) of 25-29.9 and 30-39.9, respectively. Accuracy tests and regression analyses were performed to evaluate the criterion validity of low CC for predicting length of stay (LOS) and readmission. RESULTS: A total of 248 inpatients were evaluated (69.7 [standard deviation (SD) 7.2]; 59.7% men). Among them, 31% had a low CC. A low CC (crude and adjusted for BMI) showed poor performance in predicting LOS and readmission. In the adjusted analysis, older patients with low CC had a 2.45-fold increased risk of LOS ≥ 4 days. CONCLUSION: Low CC did not perform well in predicting negative outcomes in older patients with solid tumors. However, low CC was positively associated with LOS.

Infectivity of Wild-Bird Origin Influenza A Viruses in Minnesota Wetlands across Seasons.

The environmental tenacity of influenza A viruses (IAVs) in the environment likely plays a role in their transmission; IAVs are able to remain infectious in aquatic habitats and may have the capacity to seed outbreaks when susceptible wild bird hosts utilize these same environments months or even seasons later. Here, we aimed to assess the persistence of low-pathogenicity IAVs from naturally infected ducks in Northwestern Minnesota through a field experiment. Viral infectivity was measured using replicate samples maintained in distilled water in a laboratory setting as well as in filtered water from four natural water bodies maintained in steel perforated drums (hereafter, mesocosms) within the field from autumn 2020 to spring 2021. There was limited evidence for the extended persistence of IAVs held in mesocosms; from 65 initial IAV-positive samples, only six IAVs persisted to at least 202 days in the mesocosms compared to 17 viruses persisting at least this long when held under temperature-controlled laboratory settings in distilled water. When accounting for the initial titer of samples, viruses detected at a higher concentration at the initiation of the experiment persisted longer than those with a lower starting titer. A parallel experimental laboratory model was used to further explore the effects of water type on viral persistence, and the results supported the finding of reduced tenacity of IAVs held in mesocosms compared to distilled water. The results of this investigation provide evidence that many factors, including temperature and physicochemical properties, impact the duration of viral infectivity in natural settings, further extending our understanding of the potential and limitations of environmental-based methodologies to recover infectious IAVs.

Molecular sexing of birds using quantitative PCR (qPCR) of sex-linked genes and logistic regression models.

The ability to sex individuals is an important component of many behavioural and ecological investigations and provides information for demographic models used in conservation and species management. However, many birds are difficult to sex using morphological characters or traditional molecular sexing methods. In this study, we developed probabilistic models for sexing birds using quantitative PCR (qPCR) data. First, we quantified distributions of gene copy numbers at a set of six sex-linked genes, including the sex-determining gene DMRT1, for individuals across 17 species and seven orders of birds (n = 150). Using these data, we built predictive logistic models for sex identification and tested their performance with independent samples from 51 species and 13 orders (n = 209). Models using the two loci most highly correlated with sex had greater accuracy than models using the full set of sex-linked loci, across all taxonomic levels of analysis. Sex identification was highly accurate when individuals to be assigned were of species used in model building. Our analytical approach was widely applicable across diverse neognath bird lineages spanning millions of years of evolutionary divergence. Unlike previous methods, our probabilistic framework incorporates uncertainty around qPCR measurements as well as biological variation within species into decision-making rules. We anticipate that this method will be useful for sexing birds, including those of high conservation concern and/or subsistence value, that have proven difficult to sex using traditional approaches. Additionally, the general analytical framework presented in this paper may also be applicable to other organisms with sex chromosomes.

Identifying genetic differences between bipolar disorder and major depression through multiple GWAS.

Background: Accurate diagnosis of bipolar disorder (BD) is difficult in clinical practice, with an average delay between symptom onset and diagnosis of about 7 years. A key reason is that the first manic episode is often preceded by a depressive one, making it difficult to distinguish BD from unipolar major depressive disorder (MDD). Aims: Here, we use genome-wide association analyses (GWAS) to identify differential genetic factors and to develop predictors based on polygenic risk scores that may aid early differential diagnosis. Methods: Based on individual genotypes from case-control cohorts of BD and MDD shared through the Psychiatric Genomics Consortium, we compile case-case-control cohorts, applying a careful merging and quality control procedure. In a resulting cohort of 51,149 individuals (15,532 BD cases, 12,920 MDD cases and 22,697 controls), we perform a variety of GWAS and polygenic risk scores (PRS) analyses. Results: While our GWAS is not well-powered to identify genome-wide significant loci, we find significant SNP-heritability and demonstrate the ability of the resulting PRS to distinguish BD from MDD, including BD cases with depressive onset. We replicate our PRS findings, but not signals of individual loci in an independent Danish cohort (iPSYCH 2015 case-cohort study, N=25,966). We observe strong genetic correlation between our case-case GWAS and that of case-control BD. Conclusions: We find that MDD and BD, including BD with a depressive onset, are genetically distinct. Further, our findings support the hypothesis that Controls - MDD - BD primarily lie on a continuum of genetic risk. Future studies with larger and richer samples will likely yield a better understanding of these findings and enable the development of better genetic predictors distinguishing BD and, importantly, BD with depressive onset from MDD.

Animal models of Lyme carditis. Understanding how to study a complex disease.

Lyme carditis, a well-established manifestation of Lyme disease, has been studied in animal models to improve understanding of its pathogenesis. This review synthesizes existing literature on these models and associated disease mechanisms. Searches in MEDLINE, Embase, BIOSIS, and Web of Science yielded 53 articles (47 mice models and 6 other animal models). Key findings include: 1) Onset of carditis correlates with spirochete localization in the heart; 2) Carditis occurs within 10 days of infection, progressing to peak inflammation within 30 days; 3) Infiltrates were predominantly composed of Mac-1+ macrophages and were associated with increases in TNF-α, IL-1 and IL-12 cytokines; 4) Resolution of inflammation was primarily mediated by lymphocytes; 5) Immune system is a double-edged sword: it can play a role in the progression and severity of carditis, but can also have a protective effect. Animal models offer valuable insights into the evolution and pathophysiologic mechanisms of Lyme carditis.

Safety Assessment of Alkane Diols as Used in Cosmetics.

The Expert Panel for Cosmetic Ingredient Safety (Panel) assessed the safety of 10 alkane diol ingredients as used in cosmetics. The alkane diols are structurally related to each other as small diols, and most are reported to function in cosmetics as solvents. The Panel reviewed the relevant data for these ingredients, and concluded that seven alkane diols are safe in cosmetics in the present practices of use and concentration described in this safety assessment, but that the available data are insufficient to make a determination of safety for three ingredients, namely 1,4-Butanediol, 2,3-Butanediol, and Octanediol.

Safety Assessment of Zinc Salts as Used in Cosmetics.

The Expert Panel for Cosmetic Ingredient Safety (Panel) assessed the safety of 27 inorganic and organometallic zinc salts as used in cosmetic formulations; these salts are specifically of the 2+ (II) oxidation state cation of zinc. These ingredients included in this report have various reported functions in cosmetics, including hair conditioning agents, skin conditioning agents, cosmetic astringents, cosmetic biocides, preservatives, oral care agents, buffering agents, bulking agents, chelating agents, and viscosity increasing agents. The Panel reviewed the relevant data for these ingredients, and concluded that these 27 ingredients are safe in cosmetics in the present practices of use and concentration described in this safety assessment when formulated to be non-irritating.

Multi-ancestry genome-wide association study of major depression aids locus discovery, fine mapping, gene prioritization and causal inference.

Most genome-wide association studies (GWAS) of major depression (MD) have been conducted in samples of European ancestry. Here we report a multi-ancestry GWAS of MD, adding data from 21 cohorts with 88,316 MD cases and 902,757 controls to previously reported data. This analysis used a range of measures to define MD and included samples of African (36% of effective sample size), East Asian (26%) and South Asian (6%) ancestry and Hispanic/Latin American participants (32%). The multi-ancestry GWAS identified 53 significantly associated novel loci. For loci from GWAS in European ancestry samples, fewer than expected were transferable to other ancestry groups. Fine mapping benefited from additional sample diversity. A transcriptome-wide association study identified 205 significantly associated novel genes. These findings suggest that, for MD, increasing ancestral and global diversity in genetic studies may be particularly important to ensure discovery of core genes and inform about transferability of findings.

Screening and Management Recommendations for Type 2 Diabetes in Women With Breast Cancer.

Breast cancer increases the risk of type 2 diabetes 1.07- to 4.27-fold, depending on patient and treatment characteristics, such as postmenopausal status, hormone therapy, and treatment with adjuvant chemotherapy. We evaluated the current evidence and considered the role of increased screening for type 2 diabetes in this at-risk population. This narrative review was conducted using Embase and MEDLINE databases. Keywords including diabetes and breast cancer were used. Articles were limited to those published in English between 2000 and 2022. It appears that the increased risk of diabetes begins at or just after breast cancer diagnosis, and remains elevated for at least 10 to 15 years, with greatest risk in the first 2 years after diagnosis. Subsets of patients with breast cancer appear to be at higher risk of developing type 2 diabetes, including those who were treated with adjuvant chemotherapy or hormone therapy. Further investigation is needed to develop specific screening recommendations for this population. If screening is performed with a glycated hemoglobin test during breast cancer treatment, then hemoglobin should be measured at the same time given the association of breast cancer therapy with anemia. Presence of breast cancer should not be a major factor when choosing among available antihyperglycemic agents. Overall, patients with breast cancer appear to be at an increased risk of developing type 2 diabetes. This increased risk suggests the need for further investigation to develop specific screening recommendations for this at-risk population.

Molecular detection and characterization of highly pathogenic H5N1 clade 2.3.4.4b avian influenza viruses among hunter-harvested wild birds provides evidence for three independent introductions into Alaska.

We detected and characterized highly pathogenic avian influenza viruses among hunter-harvested wild waterfowl inhabiting western Alaska during September-October 2022 using a molecular sequencing pipeline applied to RNA extracts derived directly from original swab samples. Genomic characterization of 10 H5 clade 2.3.4.4b avian influenza viruses detected with high confidence provided evidence for three independent viral introductions into Alaska. Our results highlight the utility and some potential limits of applying molecular processing approaches directly to RNA extracts from original swab samples for viral research and monitoring.

Attitudes Toward Utilization of Minimally Invasive Cosmetic Procedures in Black Women: Results of a Cross-sectional Survey.

This cross-sectional study was designed to better understand perceptions of beauty, antiaging, and cosmetic procedures among young Black women, particularly social media users. An in-depth questionnaire was developed and administered via social media platforms to Black women in the United States (N=352). Study participants were asked about their top cosmetic skin concerns, prior and current usage of minimally invasive cosmetic procedures, and their attitudes toward obtaining such procedures in the future. Attitudes regarding beauty and self-perceived aging also were obtained to better understand how this demographic views beauty with regard to aging. All results were further stratified by age. Our findings suggest that perceptions of antiaging, particularly with regard to sunscreen use, are changing among younger Black women.

Adipose tissue eQTL meta-analysis reveals the contribution of allelic heterogeneity to gene expression regulation and cardiometabolic traits.

Complete characterization of the genetic effects on gene expression is needed to elucidate tissue biology and the etiology of complex traits. Here, we analyzed 2,344 subcutaneous adipose tissue samples and identified 34K conditionally distinct expression quantitative trait locus (eQTL) signals in 18K genes. Over half of eQTL genes exhibited at least two eQTL signals. Compared to primary signals, non-primary signals had lower effect sizes, lower minor allele frequencies, and less promoter enrichment; they corresponded to genes with higher heritability and higher tolerance for loss of function. Colocalization of eQTL with conditionally distinct genome-wide association study signals for 28 cardiometabolic traits identified 3,605 eQTL signals for 1,861 genes. Inclusion of non-primary eQTL signals increased colocalized signals by 46%. Among 30 genes with ≥2 pairs of colocalized signals, 21 showed a mediating gene dosage effect on the trait. Thus, expanded eQTL identification reveals more mechanisms underlying complex traits and improves understanding of the complexity of gene expression regulation.

Proteome-Wide Association Studies for Blood Lipids and Comparison with Transcriptome-Wide Association Studies.

Blood lipid traits are treatable and heritable risk factors for heart disease, a leading cause of mortality worldwide. Although genome-wide association studies (GWAS) have discovered hundreds of variants associated with lipids in humans, most of the causal mechanisms of lipids remain unknown. To better understand the biological processes underlying lipid metabolism, we investigated the associations of plasma protein levels with total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL), and low-density lipoprotein cholesterol (LDL) in blood. We trained protein prediction models based on samples in the Multi-Ethnic Study of Atherosclerosis (MESA) and applied them to conduct proteome-wide association studies (PWAS) for lipids using the Global Lipids Genetics Consortium (GLGC) data. Of the 749 proteins tested, 42 were significantly associated with at least one lipid trait. Furthermore, we performed transcriptome-wide association studies (TWAS) for lipids using 9,714 gene expression prediction models trained on samples from peripheral blood mononuclear cells (PBMCs) in MESA and 49 tissues in the Genotype-Tissue Expression (GTEx) project. We found that although PWAS and TWAS can show different directions of associations in an individual gene, 40 out of 49 tissues showed a positive correlation between PWAS and TWAS signed p-values across all the genes, which suggests a high-level consistency between proteome-lipid associations and transcriptome-lipid associations.

Exploring attitudes of healthcare professionals towards those with fibromyalgia: A Q-methodological approach.

Fibromyalgia remains a difficult condition to diagnose and treat. Research suggests that this leads to frustrating experiences for service users and healthcare professionals. This has led to negative healthcare professional attitudes towards working with those with fibromyalgia. The research to date reports negative attitudes and predominantly investigates attitudes of primary care physicians. This study explores the attitudes of a range of healthcare professionals towards those diagnosed with fibromyalgia. Using Q-methodology, 27 healthcare professionals completed a sorting task and questionnaire to prioritise statements relating to a range of different attitudes towards service users. All participants significantly loaded onto three factors that explained a total of 64% of the data variance. Factor 1 reflected the attitude 'Service users with fibromyalgia are no different to other service users and I enjoy working with them'. Factor 2 reflected the attitude 'Service users with fibromyalgia are inaccurate informants of their own condition due to lack of understanding of their condition and are not likely to engage in treatments'. Factor 3 reflected the attitude 'Service users with fibromyalgia are trustworthy with a lot of clinical problems [but I lack confidence in specialist skills to support them]'. Contrary to the current literature, there appears to be supportive attitudes from healthcare professionals towards service users diagnosed with fibromyalgia. Increased specialised training, clinical exposure to working with fibromyalgia and reflective practice spaces were identified as elements that could improve healthcare professional attitudes.

Metabolome-wide Mendelian randomization characterizes heterogeneous and shared causal effects of metabolites on human health.

Metabolites are small molecules that are useful for estimating disease risk and elucidating disease biology. Nevertheless, their causal effects on human diseases have not been evaluated comprehensively. We performed two-sample Mendelian randomization to systematically infer the causal effects of 1,099 plasma metabolites measured in 6,136 Finnish men from the METSIM study on risk of 2,099 binary disease endpoints measured in 309,154 Finnish individuals from FinnGen. We identified evidence for 282 causal effects of 70 metabolites on 183 disease endpoints (FDR<1%). We found 25 metabolites with potential causal effects across multiple disease domains, including ascorbic acid 2-sulfate affecting 26 disease endpoints in 12 disease domains. Our study suggests that N-acetyl-2-aminooctanoate and glycocholenate sulfate affect risk of atrial fibrillation through two distinct metabolic pathways and that N-methylpipecolate may mediate the causal effect of N6, N6-dimethyllysine on anxious personality disorder. This study highlights the broad causal impact of plasma metabolites and widespread metabolic connections across diseases.

Complementarity of nutritional assessment tools to predict prolonged hospital stay and readmission in older patients with solid tumors: A secondary analysis of a cohort study.

OBJECTIVE: The aim of this study was to investigate the complementarity of five nutritional risk screening tools (Nutritional Risk Screening 2002 [NRS-2002], Malnutrition Screening Tool [MST], Malnutrition Universal Screening Tool [MUST], Mini-Nutritional Assessment-Short Form [MNA-SF], and Patient-Generated Subjective Global Assessment SF [PG-SGA SF]) combined with three malnutrition diagnostic tools (SGA, PG-SGA, and Global Leadership Initiative on Malnutrition [GLIM]) and their ability to predict poor clinical outcomes in older patients with cancer. METHODS: Using data collected within 48 h of hospital admission, we conducted a prospective cohort study on nutritional risk (NRS-2002, MST, MUST, MNA-SF, and PG-SGA SF) and the presence of malnutrition (SGA, PG-SGA, and GLIM). Patients were grouped according to their nutritional risk and malnutrition status. Accuracy tests and logistic regression analysis were used to evaluate the ability of the combined tools to predict hospital length of stay and readmission. We evaluated 248 older patients (69.7 ± 7.2 y of age, 59.7% men; 27.4% with gastrointestinal tumors). The median length of stay was 4 d (3-9 d), and 65.3% of patients remained hospitalized for ≥ 4 d. RESULTS: The NRS-2002 combined with SGA and MST combined with SGA and GLIM had the highest specificity (> 80%) for predicting hospitalization. Nutritional risk assessed by MNA-SF and malnutrition assessed by PG-SGA were associated with 2.48- and 6.04-fold increased likelihood of hospitalization (≥ 4 d) and readmission (60 d), respectively. CONCLUSION: Concomitant application of MNA-SF (specific for older patients) with PG-SGA (specific for patients with cancer) might enhance the ability to predict length of stay and readmission in hospitalized older patients with solid tumors.

Accuracy of the GLIM Criteria and SGA Compared to PG-SGA for the Diagnosis of Malnutrition and Its Impact on Prolonged Hospitalization: A Prospective Study in Patients with Cancer.

BACKGROUND: Early assessment of malnutrition in cancer patients is essential. This study analyzed the accuracy of the Global Leadership Initiative on Malnutrition (GLIM) and the Subjective Global Assessment (SGA), in diagnosing malnutrition, considering the Patient Generated-SGA (PG-SGA) as a reference, and the impact of malnutrition on hospital days. METHODS: We conducted a prospective cohort study in 183 patients with gastrointestinal, head and neck, and lung cancer. Malnutrition was assessed within 48 h, of hospital admission according to the SGA, PG-SGA, and GLIM. Accuracy tests and regression analysis were performed to assess the criterion validity of the GLIM and SGA for diagnosing malnutrition. RESULTS: Malnutrition was diagnosed in 57.3% (SGA), 86.3% (PG-SGA), and 74.9% (GLIM) of the inpatients. The median of hospitalization was 6 (3-11) days, with 47% hospitalized > 6 day. The SGA presented the best accuracy (AUC = 0.832) than the GLIM (AUC = 0.632) compared to PG-SGA. Patients diagnosed with malnutrition by SGA, GLIM, and PG-SGA remained hospitalized for 2.13, 3.19, and 4.56 day more than well-nourished patients, respectively. CONCLUSION: Compared to PG-SGA, the SGA presents good accuracy and adequate specificity (>80%). Malnutrition evaluated by SGA, PG-SGA, and GLIM was associated with more days of hospitalization.

Resident Trainee Access and Barriers to Routine Health Services in the Military Health System.

OBJECTIVE: Resident physician wellness has been a highly contentious topic in graduate medical education over the past 2 decades. Physicians, including residents and attending physicians, are more likely than other professionals to work through illness and delay necessary healthcare screening appointments. Potential reasons for underutilization of health care include-unpredictable work hours, limited time, concerns about confidentiality, poor support from training programs, and apprehension about the impact on their peers. The goal of this study was to evaluate access to health care amongst resident physicians within a large military training facility. DESIGN: This is an observational study using Department of Defense approved software to distribute an anonymous ten question survey on routine health care practices of residents. The survey was distributed to a total of 240 active-duty military resident physicians at a large tertiary military medical center. RESULTS: One hundred seventy-eight residents completed the survey with a 74% response rate. Residents from 15 specialty areas responded. Compared to male counterparts', female residents were more likely to miss routine scheduled health care appointments to include, behavioral health appointments (54.2% vs 28%, p < 0.01). Female residents were more likely to report that attitudes toward missing clinical duties for health care appointments impacted their decision to start or add to their family more than male coresidents (32.3% vs 18.3%, p = 0.03). Surgical residents are also more likely to miss routine screening appointments or scheduled follow ups than residents in nonsurgical training programs; (84.0-88% compared to 52.4%-62.8%) respectively. CONCLUSIONS: Resident health and wellness have long been an issue, with resident physical and mental health being negatively impacted during residency. Our study notes that residents in the military system also face barriers accessing routine health care. Female surgical residents being the demographic most significantly impacted. Our survey highlights cultural attitudes in military graduate medical education regarding the prioritization of personal health, and the negative impact that can have on residents' utilization of care. Our survey also raises concerns particularly amongst female surgical residents, that these attitudes may impact career advancement, as well as influence their decision to start or add to their families.

Environmental antimicrobial resistance gene detection from wild bird habitats using two methods: A commercially available culture-independent qPCR assay and culture of indicator bacteria followed by whole-genome sequencing.

OBJECTIVES: A variety of methods have been developed to detect antimicrobial resistance (AMR) in different environments to better understand the evolution and dissemination of this public health threat. Comparisons of results generated using different AMR detection methods, such as quantitative PCR (qPCR) and whole-genome sequencing (WGS), are often imperfect, and few studies have analysed samples in parallel to evaluate differences. In this study, we compared bacterial culture and WGS to a culture-independent commercially available qPCR assay to evaluate the concordance between methods and the utility of each in answering research questions regarding the presence and epidemiology of AMR in wild bird habitats. METHODS: We first assessed AMR gene detection using qPCR in 45 bacterial isolates from which we had existing WGS data. We then analysed 52 wild bird faecal samples and 9 spatiotemporally collected water samples using culture-independent qPCR and WGS of phenotypically resistant indicator bacterial isolates. RESULTS: Overall concordance was strong between qPCR and WGS of bacterial isolates, although concordance differed among antibiotic classes. Analysis of wild bird faecal and water samples revealed that more samples were determined to be positive for AMR via qPCR than via culture and WGS of bacterial isolates, although qPCR did not detect AMR genes in two samples from which phenotypically resistant isolates were found. CONCLUSIONS: Both qPCR and culture followed by sequencing may be effective approaches for characterising AMR genes harboured by wild birds, although data streams produced using these different tools may have advantages and disadvantages that should be considered given the application and sample matrix.

Leave No Trace? Ecological and anthropogenic determinants of antibiotic resistant bacteria in a recreational alpine environment.

Antibiotic resistant bacteria (ARB) have been detected in remote environments, but the degree to which their presence is due to anthropogenic contamination remains unclear. Here, anthropogenic and ecological determinants of ARB were characterized in remote and highly visited areas of Rocky Mountain National Park in the United States. Soil and water samples were collected from 29 sites once a month for three months and measured for bacteria resistant to seven antibiotics with flow cytometry. A novel index of the likelihood of human presence (HPI) was generated for estimating human impact on ARB abundance. The HPI accounted for 44% of variation in ARB abundance in water samples (p < 0.0001) and 51% of variation in soil samples (p < 0.00001). Human presence index was illustrated as a reliable predictor of ARB abundance despite a tendency to underpredict at higher levels of human impact. Ecological determinants such as temperature, elevation, slope, and aspect were also found to be significantly associated with ARB abundance. These findings suggest that human presence drives the abundance of ARB in Rocky Mountain National Park, but ecological variables play a significant role in their presence and dispersal.