Clinical and genetic contributions to medical comorbidity in bipolar disorder: a study using electronic health records-linked biobank data.

Bipolar disorder is a chronic and complex polygenic disease with high rates of comorbidity. However, the independent contribution of either diagnosis or genetic risk of bipolar disorder to the medical comorbidity profile of individuals with the disease remains unresolved. Here, we conducted a multi-step phenome-wide association study (PheWAS) of bipolar disorder using phenomes derived from the electronic health records of participants enrolled in the Mayo Clinic Biobank and the Mayo Clinic Bipolar Disorder Biobank. First, we explored the conditions associated with a diagnosis of bipolar disorder by conducting a phenotype-based PheWAS followed by LASSO-penalized regression to account for correlations within the phenome. Then, we explored the conditions associated with bipolar disorder polygenic risk score (BD-PRS) using a PRS-based PheWAS with a sequential exclusion approach to account for the possibility that diagnosis, instead of genetic risk, may drive such associations. 53,386 participants (58.7% women) with a mean age at analysis of 67.8 years (SD = 15.6) were included. A bipolar disorder diagnosis (n = 1479) was associated with higher rates of psychiatric conditions, injuries and poisonings, endocrine/metabolic and neurological conditions, viral hepatitis C, and asthma. BD-PRS was associated with psychiatric comorbidities but, in contrast, had no positive associations with general medical conditions. While our findings warrant confirmation with longitudinal-prospective studies, the limited associations between bipolar disorder genetics and medical conditions suggest that shared environmental effects or environmental consequences of diagnosis may have a greater impact on the general medical comorbidity profile of individuals with bipolar disorder than its genetic risk.

Antarctic marine sediment as a source of filamentous fungi-derived antimicrobial and antitumor compounds of pharmaceutical interest.

Antarctica harbors a microbial diversity still poorly explored and of inestimable biotechnological value. Cold-adapted microorganisms can produce a diverse range of metabolites stable at low temperatures, making these compounds industrially interesting for biotechnological use. The present work investigated the biotechnological potential for antimicrobial and antitumor activity of filamentous fungi and bacteria isolated from marine sediment samples collected at Deception Island, Antarctica. A total of 89 microbial isolates were recovered from marine sediments and submitted to an initial screening for L-glutaminase with antitumoral activity and for antimicrobial metabolites. The isolates Pseudogymnoascus sp. FDG01, Pseudogymnoascus sp. FDG02, and Penicillium sp. FAD33 showed potential antiproliferative action against human pancreatic carcinoma cells while showing no toxic effect on non-tumor cells. The microbial extracts from unidentified three bacteria and four filamentous fungi showed antibacterial activity against at least one tested pathogenic bacterial strain. The isolate FDG01 inhibited four bacterial species, while the isolate FDG01 was active against Micrococcus luteus in the minimal inhibitory concentration of 0.015625 µg mL -1. The results pave the way for further optimization of enzyme production and characterization of enzymes and metabolites found and reaffirm Antarctic marine environments as a wealthy source of compounds potentially applicable in the healthcare and pharmaceutical industry.

Changes in the expression of genes encoding xanthophyl acyltransferases during the postharvest ripening of avocado (Persea americana) fruit.

BACKGROUND: Avocado fruit is rich in xanthophylls, which have been related to positive effects on human health. Xanthophyl acetyltransferases (XATs) are enzymes catalyzing the esterification of carboxylic acids to the hydroxyl group of the xanthophyll molecule. This esterification is thought to increase the lipophilic nature of the xanthophyll and its stability in a lipophilic environment. Studies on XATs in fruits are very scarce, and no studies had been carried out in avocado fruit during postharvest. The objective of this work was to investigate the changes in the expression of genes encoding XAT, during avocado fruit ripening. RESULTS: Avocado fruits were obtained from a local market and stored at 15 °C for 8 days. The fruit respiration rate, ethylene production, and fruit peel's color space parameters (L*, a*, b*) were measured during storage. Fruit mesocarp samples were taken after 1, 3, 5, and 7 days of storage and frozen with liquid nitrogen. Total RNA was extracted from fruit mesocarp, and the quantification of the two genes designated as COGE_ID: 936743791 and COGE_ID: 936800185 encoding XATs was performed with real-time quantitative reverse transcription polymerase chain reaction using actin as a reference gene. The presence of a climacteric peak and large changes in color were recorded during postharvest. The two genes studied showed a large expression after 3 days of fruit storage. CONCLUSIONS: We conclude that during the last stages of ripening in avocado fruit there was an active esterification of xanthophylls with carboxylic acids, which suggests the presence of esterified xanthophylls in the fruit mesocarp. © 2024 Society of Chemical Industry.

Impact of health insurance on the use of oral health services in the Peruvian population 2015-2019.

BACKGROUND: The high treatment cost of oral diseases is a barrier for accessing oral health services (OHS), particularly in low-income countries. Therefore, this study aimed to evaluate the impact of health insurance on the use of OHS in the Peruvian population from 2015 to 2019. METHODS: We conducted a prospective, longitudinal study of secondary data using the National Household Survey (ENAHO) 2015-2019 panel databases, which collected information from the same participants during each of the five years. The dependent variable was the use of OHS in the three months prior to the survey (yes/no). The independent variable was health insurance affiliation (four years or less/all five years). Both were measured by survey questions. Generalized estimating equation (GEE) Poisson regression models with robust standard errors were used to estimate the relative risk (RR) associated with use of OHS. RESULTS: We included 4064 individuals distributed in 1847 households, who responded to the survey during each of the five years. The adjusted GEE model showed that those who had health insurance during all five years without interruption were more likely to attend OHS than those who had insurance for four years or less (adjusted relative risk [aRR]: 1.30; 95%CI: 1.13-1.50). In addition, we carried out a sensitivity analysis by recategorizing the independent variable into three categories (never/some years/ all five years), which also showed (aRR: 1.45; 95%CI: 1.11-1.89) that participants with health insurance during all five years were more likely to have used OHS than those who never had insurance. CONCLUSION: Therefore, in the Peruvian context, health insurance affiliation was associated with greater use of OHS. The panel data used derives from a subsample of consecutive nationally representative samples, which may have led to a loss of representativeness. Furthermore, the data was collected between 2015 and 2019, prior to the onset of the COVID-19 pandemic, and insurance conditions may have changed.

Pore-forming activity of S. pneumoniae pneumolysin disrupts the paracellular localization of the epithelial adherens junction protein E-cadherin.

Streptococcus pneumoniae, a common cause of community-acquired bacterial pneumonia, can cross the respiratory epithelial barrier to cause lethal septicemia and meningitis. S. pneumoniae pore-forming toxin pneumolysin (PLY) triggers robust neutrophil (PMN) infiltration that promotes bacterial transepithelial migration in vitro and disseminated disease in mice. Apical infection of polarized respiratory epithelial monolayers by S. pneumoniae at a multiplicity of infection (MOI) of 20 resulted in recruitment of PMNs, loss of 50% of the monolayer, and PMN-dependent bacterial translocation. Reducing the MOI to 2 decreased PMN recruitment two-fold and preserved the monolayer, but apical-to-basolateral translocation of S. pneumoniae remained relatively efficient. At both MOI of 2 and 20, PLY was required for maximal PMN recruitment and bacterial translocation. Co-infection by wild-type S. pneumoniae restored translocation by a PLY-deficient mutant, indicating that PLY can act in trans. Investigating the contribution of S. pneumoniae infection on apical junction complexes in the absence of PMN transmigration, we found that S. pneumoniae infection triggered the cleavage and mislocalization of the adherens junction (AJ) protein E-cadherin. This disruption was PLY-dependent at MOI of 2 and was recapitulated by purified PLY, requiring its pore-forming activity. In contrast, at MOI of 20, E-cadherin disruption was independent of PLY, indicating that S. pneumoniae encodes multiple means to disrupt epithelial integrity. This disruption was insufficient to promote bacterial translocation in the absence of PMNs. Thus, S. pneumoniae triggers cleavage and mislocalization of E-cadherin through PLY-dependent and -independent mechanisms, but maximal bacterial translocation across epithelial monolayers requires PLY-dependent neutrophil transmigration.

Antidepressant-Associated Treatment Emergent Mania: A Meta-Analysis to Guide Risk Modeling Pharmacogenomic Targets of Potential Clinical Value.

BACKGROUND: The purpose of this study was to review the association between the SLC6A4 5-HTTLPR polymorphism and antidepressant (AD)-associated treatment emergent mania (TEM) in bipolar disorder alongside starting a discussion on the merits of developing risk stratification models to guide when not to provide AD treatment for bipolar depression. METHODS: Studies that examined the association between clinical and genetic risk factors, specifically monoaminergic transporter genetic variation, and TEM were identified. A meta-analysis was performed using the odds ratio to estimate the effect size under the Der-Simonian and Laird model. RESULTS: Seven studies, referencing the SLC6A4 5-HTTLPR polymorphism and TEM (total N = 1578; TEM+ =594, TEM- = 984), of 142 identified articles were included. The time duration between the start of the AD to emergence of TEM ranged from 4 to 12 weeks. There was a nominally significant association between the s allele of the 5-HTTLPR polymorphism and TEM (odds ratio, 1.434; 95% confidence interval, 1.001-2.055; P = 0.0493; I2 = 52%). No studies have investigated norepinephrine or dopamine transporters. CONCLUSION: Although the serotonin transporter genetic variation is commercially available in pharmacogenomic decision support tools, greater efforts, more broadly, should focus on complete genome-wide approaches to determine genetic variants that may contribute to TEM. Moreover, these data are exemplary to the merits of developing risk stratification models, which include both clinical and biological risk factors, to guide when not to use ADs in bipolar disorder. Future studies will need to validate new risk models that best inform the development of personalized medicine best practices treating bipolar depression.

Heuristics and optimal solutions to the breadth-depth dilemma.

In multialternative risky choice, we are often faced with the opportunity to allocate our limited information-gathering capacity between several options before receiving feedback. In such cases, we face a natural trade-off between breadth-spreading our capacity across many options-and depth-gaining more information about a smaller number of options. Despite its broad relevance to daily life, including in many naturalistic foraging situations, the optimal strategy in the breadth-depth trade-off has not been delineated. Here, we formalize the breadth-depth dilemma through a finite-sample capacity model. We find that, if capacity is small (∼10 samples), it is optimal to draw one sample per alternative, favoring breadth. However, for larger capacities, a sharp transition is observed, and it becomes best to deeply sample a very small fraction of alternatives, which roughly decreases with the square root of capacity. Thus, ignoring most options, even when capacity is large enough to shallowly sample all of them, is a signature of optimal behavior. Our results also provide a rich casuistic for metareasoning in multialternative decisions with bounded capacity using close-to-optimal heuristics.

Association between the Neutrophil-to-Lymphocyte Ratio and Inpatient Mortality in Hospitalized Older Veterans with COVID-19 Infection.

OBJECTIVES: Determine the association of high neutrophil-to-lymphocyte ratio (NLR) values with inpatient mortality and other outcomes in older veterans hospitalized with coronavirus disease 2019 (COVID-19). METHODS: This was a retrospective, multicenter, cohort study of hospitalized adults, with laboratory-confirmed COVID-19 infection who were studied for 1 year after discharge or until death. The NLR was categorized into tertiles, and we determined frailty status with the 31-item Veterans Affairs Frailty Index. Multivariate logistic regression and adjusted odds ratios (aORs) with 95% confidence intervals (CIs) were performed to assess the association between NLR and clinical outcomes. RESULTS: The study included 615 hospitalized adult veterans, mean age 66.12 (standard deviation 14.79) years, 93.82% (n = 577) male, 57.56% (n = 354) White, 81.0% (n = 498) non-Hispanic, median body mass index of 30.70 (interquartile range 25.64-34.99, standard deviation 7.13), and median length of stay of 8 days (interquartile range 3-15). Individuals in the middle and upper tertile groups had higher inpatient mortality (8.37%, n = 17 and 18.36%, n = 38, respectively) as compared with the lower tertile (2.93%, n = 6, P < 0.001). Compared with the lowest tertile, the middle and upper tertiles had a higher risk of inpatient mortality (aOR 3.75, 95% CI 1.38-10.21, P = 0.01, and aOR 8.13, 95% CI 3.18-20.84, P < 0.001, respectively). The highest tertile had a higher odds of intensive care unit admission (aOR 4.47, 95% CI 2.33-8.58, P < 0.001) and intensive care unit transfer (aOR 3.54, 95% CI 1.84-6.81, P < 0.001). CONCLUSIONS: The NLR score is a clinically useful tool to predict in-hospital mortality in older patients with COVID-19.

An "epitomic" analysis of the specificity of conformation-dependent, anti-Aß amyloid monoclonal antibodies.

Antibodies against Aß amyloid are indispensable research tools and potential therapeutics for Alzheimer's disease. They display several unusual properties, such as specificity for aggregated forms of the peptide, the ability to distinguish polymorphic aggregate structures, and the ability to recognize generic aggregation-related epitopes formed by unrelated amyloid sequences. Understanding the mechanisms underlying these unusual properties and the structures of their corresponding epitopes is crucial for the understanding why antibodies display different therapeutic activities and for the development of more effective therapeutic agents. Here we employed a novel "epitomic" approach to map the fine structure of the epitopes of 28 monoclonal antibodies against amyloid-beta using immunoselection of random sequences from a phage display library, deep sequencing, and pattern analysis to define the critical sequence elements recognized by the antibodies. Although most of the antibodies map to major linear epitopes in the amino terminal 1 to 14 residues of Aß, the antibodies display differences in the target sequence residues that are critical for binding and in their individual preferences for nontarget residues, indicating that the antibodies bind to alternative conformations of the sequence by different mechanisms. Epitomic analysis also identifies discontinuous, nonoverlapping sequence Aß segments that may constitute the conformational epitopes that underlie the aggregation specificity of antibodies. Aggregation-specific antibodies recognize sequences that display a significantly higher predicted propensity for forming amyloid than antibodies that recognize the monomer, indicating that the ability of random sequences to aggregate into amyloid is a critical element of their binding mechanism.

Introducing the Catalytic Amination of Silanes via Nitrene Insertion.

The direct functionalization of Si-H bonds by the nitrene insertion methodology is described. A copper(I) complex bearing a trispyrazolylborate ligand catalyzes the transfer of a nitrene group from PhI═NTs to the Si-H bond of silanes, disilanes, and siloxanes, leading to the exclusive formation of Si-NH moieties in the first example of this transformation. The process tolerates other functionalities in the substrate such as several C-H bonds and alkyne and alkene moieties directly bonded to the silicon center. Density functional theory (DFT) calculations provide a mechanistic interpretation consisting of a Si-H homolytic cleavage and subsequent rebound to the Si-centered radical.

Biomass resilience of Neotropical secondary forests.

Land-use change occurs nowhere more rapidly than in the tropics, where the imbalance between deforestation and forest regrowth has large consequences for the global carbon cycle. However, considerable uncertainty remains about the rate of biomass recovery in secondary forests, and how these rates are influenced by climate, landscape, and prior land use. Here we analyse aboveground biomass recovery during secondary succession in 45 forest sites and about 1,500 forest plots covering the major environmental gradients in the Neotropics. The studied secondary forests are highly productive and resilient. Aboveground biomass recovery after 20 years was on average 122 megagrams per hectare (Mg ha(-1)), corresponding to a net carbon uptake of 3.05 Mg C ha(-1) yr(-1), 11 times the uptake rate of old-growth forests. Aboveground biomass stocks took a median time of 66 years to recover to 90% of old-growth values. Aboveground biomass recovery after 20 years varied 11.3-fold (from 20 to 225 Mg ha(-1)) across sites, and this recovery increased with water availability (higher local rainfall and lower climatic water deficit). We present a biomass recovery map of Latin America, which illustrates geographical and climatic variation in carbon sequestration potential during forest regrowth. The map will support policies to minimize forest loss in areas where biomass resilience is naturally low (such as seasonally dry forest regions) and promote forest regeneration and restoration in humid tropical lowland areas with high biomass resilience.

The cross-sectional association of frailty with chronic past and current use of benzodiazepine drugs.

BACKGROUND: Frailty, a clinical syndrome characterized by vulnerability to stressors resulting from multisystemic loss of physiological reserve. The use of benzodiazepines in older adults has been associated with confusion, sedation, and cognitive impairment, which in turn may lead to frailty. AIMS: The purpose of this study was to determine the cross-sectional association between frailty and chronic past or current use of benzodiazepine drugs among older US Veterans. METHODS/DESIGN: This is a cross-sectional study of community-dwelling older Veterans who had determinations of frailty. Benzodiazepine prescription data were obtained via EHR. A 31-item VA Frailty Index (VA-FI) was generated at the time of the assessment. We categorized Veterans into robust (FI ≤ 0.10), pre-frail (FI 0.10-0.21), and Frail (FI ≥ 0.21). After adjusting for sociodemographic characteristics, we calculated ORs and 95% CIs using a binomial logistic regression (BLR) model to assess the cross-sectional association between benzodiazepine use and frailty. RESULTS: Population sample consisted of 17,423 Veterans, mean age 75.53 (SD = 8.03) years, 70.80% Caucasian, 97.34% male, 14,545 (83.50%) patients were non-users of benzodiazepine drugs, 2408 (13.80%) had a past use, and 470 (2.70%) were current users. In BLR, individuals with past (OR 2.51, 95% CI 2.30-2.74, p < .001) or current (OR 2.36, 95% CI 1.96-2.83, p < .001) use showed a higher association with frailty as compared to individuals who were non-users. CONCLUSIONS: The use of benzodiazepine was cross-sectionally associated with frailty in older Veterans. These results suggest that screening for frailty in patients with past or current exposure to benzodiazepine medications may be necessary for proper management.

Gap in Willingness and Access to Video Visit Use Among Older High-risk Veterans: Cross-sectional Study.

BACKGROUND: The recent shift to video care has exacerbated disparities in health care access, especially among high-need, high-risk (HNHR) adults. Developing data-driven approaches to improve access to care necessitates a deeper understanding of HNHR adults' attitudes toward telemedicine and technology access. OBJECTIVE: This study aims to identify the willingness, access, and ability of HNHR veterans to use telemedicine for health care. METHODS: WWe designed a questionnaire conducted via mail or telephone or in person. Among HNHR veterans who were identified using predictive modeling with national Veterans Affairs data, we assessed willingness to use video visits for health care, access to necessary equipment, and comfort with using technology. We evaluated physical health, including frailty, physical function, performance of activities of daily living (ADL) and instrumental ADL (IADL); mental health; and social needs, including Area Deprivation Index, transportation, social support, and social isolation. RESULTS: The average age of the 602 HNHR veteran respondents was 70.6 (SD 9.2; range 39-100) years; 99.7% (600/602) of the respondents were male, 61% (367/602) were White, 36% (217/602) were African American, 17.3% (104/602) were Hispanic, 31.2% (188/602) held at least an associate degree, and 48.2% (290/602) were confident filling medical forms. Of the 602 respondents, 327 (54.3%) reported willingness for video visits, whereas 275 (45.7%) were unwilling. Willing veterans were younger (P<.001) and more likely to have an associate degree (P=.002), be health literate (P<.001), live in socioeconomically advantaged neighborhoods (P=.048), be independent in IADLs (P=.02), and be in better physical health (P=.04). A higher number of those willing were able to use the internet and email (P<.001). Of the willing veterans, 75.8% (248/327) had a video-capable device. Those with video-capable technology were younger (P=.004), had higher health literacy (P=.01), were less likely to be African American (P=.007), were more independent in ADLs (P=.005) and IADLs (P=.04), and were more adept at using the internet and email than those without the needed technology (P<.001). Age, confidence in filling forms, general health, and internet use were significantly associated with willingness to use video visits. CONCLUSIONS: Approximately half of the HNHR respondents were unwilling for video visits and a quarter of those willing lacked requisite technology. The gap between those willing and without requisite technology is greater among older, less health literate, African American veterans; those with worse physical health; and those living in more socioeconomically disadvantaged neighborhoods. Our study highlights that HNHR veterans have complex needs, which risk being exacerbated by the video care shift. Although technology holds vast potential to improve health care access, certain vulnerable populations are less likely to engage, or have access to, technology. Therefore, targeted interventions are needed to address this inequity, especially among HNHR older adults.

Propensity Score Matching to Determine the Impact of Metformin on All-Cause Mortality in Older Veterans with Diabetes Mellitus.

OBJECTIVES: To determine whether metformin is associated with reduced all-cause mortality in older adults with diabetes mellitus as compared with insulin or sulfonylureas, and to evaluate whether the metformin cumulative exposure followed a dose-response relation. METHODS: Retrospective cohort study with propensity score matching in veterans 65 years old and older with diabetes mellitus. Patients who had new prescriptions for metformin were matched for demographic and clinical factors with patients receiving new prescriptions for insulin or sulfonylureas using propensity score matching. All-cause mortality risks were compared between metformin and insulin/sulfonylureas using multivariate Cox regression models. A similar approach was used for tertiles of cumulative metformin doses. RESULTS: A sample of 174 veterans taking metformin was matched with 174 who took insulin/sulfonylureas. Most patients were men (97.4%), White (80.45%), and their mean ± standard deviation age was 69.15 ± 7.65 years. Metformin exposure was associated with reduced risk of all-cause mortality (hazard ratio 0.57, 95% confidence interval 0.39-0.84, P = 0.005). The upper tertile of cumulative metformin exposure was associated with lower all-cause mortality in the fully adjusted model (hazard ratio 0.28, 95% confidence interval 0.10-0.77, P = 0.013). CONCLUSIONS: This propensity matching study shows that metformin exposure is associated with a lower risk of all-cause mortality. Higher metformin cumulative exposure seems to reduce the risk of all-cause mortality in older veterans with diabetes mellitus.

Two new RHD alleles with deletions spanning multiple exons.

BACKGROUND: The most common large-deletion RHD allele (RHD*01N.01) includes the entire coding sequence, intervening regions and untranslated regions. The rest of large-deletion RHD alleles reported to-date consist of single-exon deletions, such as RHD*01N.67 which includes exon 1. MATERIALS AND METHODS: Samples from two donors with RhD-negative serology yielded unclear or inconclusive results when subject to confirmatory testing on RHD genotyping arrays. To determine their RHD genotypes, genomic DNA was analyzed with a combination of allele-specific PCR, long-range PCR, Sanger sequencing, and next-generation sequencing assays. RESULTS: Allele-specific PCR failed to detect products for RHD exons 1 to 3 in one sample and RHD exons 1 to 5 in the other. A quantitative next-generation sequencing assay confirmed deletion of exons 1 to 3 and 1 to 5 respectively, and detected the absence of an RHD gene in trans in both samples. Long-range PCR and Sanger sequencing enabled identification of the breakpoints for both alleles. Both deletions start within the 5' Rhesus box (upstream of the identity region for the 1-to-3 deletion, downstream of it for the 1-to-5 deletion), and end within introns. CONCLUSIONS: Resolution of unclear or inconclusive results from targeted genotyping arrays often leads to the discovery of new alleles. The 5' Rhesus box may be a hot spot for genetic recombination events, such as the large deletions described in this report.

The cross-sectional association of frailty with past and current exposure to strong anticholinergic drugs.

BACKGROUND: Anticholinergic drugs may contribute to frailty by impairing cognitive and physical functions. Strong anticholinergic drugs in particular may have adverse effects among older adults. OBJECTIVES: Determine the association between frailty and the use of strong anticholinergic drugs among older US Veterans. METHODS: This is a cross-sectional study of community-dwelling Veterans 65 years and older who had determinations of frailty status. Prescription data for patients using strong anticholinergic medications (never/past/current) was obtained via electronic health records. A 31-item VA Frailty Index (VA-FI) was generated at the time of the assessment. We dichotomized the groups into non-frail (FI = < 0.21) and frail (FI ≥ 0.21) patients. We used binomial logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Frailty was the dependent variable and use of strong anticholinergic drugs was the independent variable. Multivariate adjustment was conducted for age, gender, race, ethnicity, marital status, and BMI. RESULTS: Population sample consisted of 17,084 Veterans who were 71.05% Caucasian, 97.34% male, and with a mean age 75.60 (SD = 8.04) years. Among the population, 9940 (58.18%) patients had no previous use of strong anticholinergic drugs, whereas 5182 (30.33%) had past exposure and 1962 (11.49%) had current exposure. In binomial logistic regression, individuals with past (OR 3.27, 95% CI 3.03-3.54, p < 0.0005) or current (OR 4.78, 95% CI 4.30-5.31, p < 0.0005) exposure showed a higher association with frailty as compared to individuals who were never exposed. CONCLUSIONS: Past and current use of strong anticholinergic drugs were associated with frailty in older Veterans. These results suggest that screening for frailty in patients with past or current exposure to strong anticholinergic medications may be necessary for proper management.

Depression but not frailty contributed to a higher risk for all-cause hospitalizations in male older veterans.

INTRODUCTION: Frailty is a state of vulnerability to stressors resulting in higher morbidity, mortality, and utilization in older adults. Depression and frailty often coexist, suggesting a bidirectional relationship that may increase the effects of each individual condition on clinical outcomes and health-care utilization in older adults. OBJECTIVE: To determine the effects of concurrent frailty and depression on all-cause hospitalizations. METHODS/DESIGN: Prospective cohort study, conducted at a Veterans Affairs (VA) Medical Center. The participants were male, community-dwelling veterans 65 years and older. From 4 January through 30 December 2016, a 46-item frailty index was generated from data obtained from the VA electronic health record. Trained staff conducted in-depth reviews of electronic health records ascertaining depression status. Patients were followed through 31 December 2017 for all-cause hospitalizations following the initial assessment of frailty. After adjusting for covariates, the association of frailty and depression with all-cause hospitalizations was determined with the Andersen-Gill model, accounting for repeated hospitalizations. RESULTS: Five hundred fifty-three male patients were part of the study, mean age 76.3 (SD = 8.2) years. One hundred eighty-one patients (32.7%) had depression diagnoses. During a median follow-up period of 530 days (interquartile range [IQR] = 245), 123 patients (22.2%) had 240 hospitalizations. Frailty status was not associated with future hospitalizations (adjusted hazard ratio [HR] = 1.61; 95% CI, 95-2.74; P > .05). Depression was associated with higher all-cause hospitalizations (adjusted HR = 1.57; 95% CI, 1.09-2.26); P = .0157). CONCLUSIONS: Depression but not frailty was significantly associated with higher rates of all-cause hospitalization. Implementing interventions that target older adults with both frailty and depression may reduce the burden of both conditions and reduce hospitalizations.

SodSAR: A Tower-Based 1-10 GHz SAR System for Snow, Soil and Vegetation Studies.

We introduce SodSAR, a fully polarimetric tower-based wide frequency (1-10 GHz) range Synthetic Aperture Radar (SAR) aimed at snow, soil and vegetation studies. The instrument is located in the Arctic Space Centre of the Finnish Meteorological Institute in Sodankylä, Finland. The system is based on a Vector Network Analyzer (VNA)-operated scatterometer mounted on a rail allowing the formation of SAR images, including interferometric pairs separated by a temporal baseline. We present the description of the radar, the applied SAR focusing technique, the radar calibration and measurement stability analysis. Measured stability of the backscattering intensity over a three-month period was observed to be better than 0.5 dB, when measuring a target with a known radar cross section. Deviations of the estimated target range were in the order of a few cm over the same period, indicating also good stability of the measured phase. Interforometric SAR (InSAR) capabilities are also discussed, and as a example, the coherence of subsequent SAR acquisitions over the observed boreal forest stand are analyzed over increasing temporal baselines. The analysis shows good conservation of coherence in particular at L-band, while higher frequencies are susceptible to loss of coherence in particular for dense vegetation. The potential of the instrument for satellite calibration and validation activities is also discussed.

Gene expression in peripheral blood in treatment-free major depression.

BACKGROUND: Peripheral gene expression of several molecular pathways has been studied in major depressive disorder (MDD) with promising results. We sought to investigate some of these genes in a treatment-free Latino sample of Mexican descent. MATERIAL AND METHODS: The sample consisted of 50 MDD treatment-free cases and 50 sex and age-matched controls. Gene expression of candidate genes of neuroplasticity (BDNF, p11, and VGF), inflammation (IL1A, IL1B, IL4, IL6, IL7, IL8, IL10, MIF, and TNFA), the canonical Wnt signaling pathway (TCF7L2, APC, and GSK3B), and mTOR, was compared in cases and controls. RNA was obtained from blood samples. We used bivariate analyses to compare subjects versus control mean mRNA quantification of target genes and lineal regression modelling to test for effects of age and body mass index on gene expression. RESULTS: Most subjects were female (66%) with a mean age of 26.7 (SD 7.9) years. Only GSK3B was differentially expressed between cases and controls at a statistically significant level (p = 0.048). TCF7L-2 showed the highest number of correlations with MDD-related traits, yet these were modest in size. DISCUSSION: GSK3B encodes a moderator of the canonical Wnt signaling pathway. It has a role in neuroplasticity, neuroprotection, depression, and other psychiatric phenotypes. We found that adding population diversity has the potential to elicit distinct peripheral gene expression markers in MDD and MDD-related traits. However, our results should only be considered as hypothesis-generating research that merits further replication in larger cohorts of similar ancestry.

Analysis of the coding sequences of clownfish reveals molecular convergence in the evolution of lifespan.

BACKGROUND: Standard evolutionary theories of aging postulate that reduced extrinsic mortality leads to evolution of longevity. Clownfishes of the genus Amphiprion live in a symbiotic relationship with sea anemones that provide protection from predators. We performed a survey and identified at least two species with a lifespan of over 20 years. Given their small size and ease of captive reproduction, clownfish lend themselves as experimental models of exceptional longevity. To identify genetic correlates of exceptional longevity, we sequenced the transcriptomes of Amphiprion percula and A. clarkii and performed a scan for positively-selected genes (PSGs). RESULTS: The PSGs that we identified in the last common clownfish ancestor were compared with PSGs detected in long-lived mole rats and short-lived killifishes revealing convergent evolution in processes such as mitochondrial biogenesis. Among individual genes, the Mitochondrial Transcription Termination Factor 1 (MTERF1), was positively-selected in all three clades, whereas the Glutathione S-Transferase Kappa 1 (GSTK1) was under positive selection in two independent clades. For the latter, homology modelling strongly suggested that positive selection targeted enzymatically important residues. CONCLUSIONS: These results indicate that specific pathways were recruited in independent lineages evolving an exceptionally extended or shortened lifespan and point to mito-nuclear balance as a key factor.