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Background: Well baby visits (WBVs) are a cornerstone of early childhood health, but few studies have examined the correlates of WBVs for socioeconomically vulnerable infants. The study objective was to identify factors related to the number of WBVs received by Medicaid-enrolled infants in the first three years of life and to present a preliminary explanatory model. Methods: We analyzed Iowa Medicaid claims files and birth certificate data for infants born in calendar year 2000 (N = 6,085). The outcome measure was the number of well baby visits (WBVs) received by Medicaid-enrolled infants between age 1 and 41 months (range: 0 to 10). An ecological health model and existing literature were used to evaluate 12 observed factors as potential WBV correlates. We ran multiple variable linear regression models with robust standard errors (α=0.05). Results: There were a number of infant, maternal, and health system factors associated with the number of WBVs received by Medicaid-enrolled infants. Infants whose mothers had a greater number of prenatal healthcare visits (ß = 0.24 to 0.28; P = .001) or were married (ß = 0.20; P = .002) received more WBVs. Having a chronic health condition (ß = 0.51; P < .0001) and enrollment in a case management program (ß = 0.48; P < .0001) were also positively associated with WBVs. Eligibility for Medicaid through the Supplemental Security Income Program (ß = −0.70; P = .001), increased maternal age (ß = −0.27 to −0.35; P = .004), higher levels of maternal education (ß = −0.18; P = .005), maternal smoking (ß = −0.13; P = .018), and enrollment in a health maintenance organization plan (ß = −1.15; P < .0001) were negatively associated with WBVs. There was a significant interaction between enrollment in a health maintenance organization plan and enrollment in a Medicaid case management program (P = .015). Maternal race, maternal alcohol use during pregnancy, and rurality were not significantly related to the number of WBVs. Conclusions: Multiple infant, maternal, and health system variables were related to the number of WBVs received by Medicaid-enrolled infants. Additional research is needed to develop strategies to optimize access to WBVs for Medicaid-enrolled infants at risk for poor use of preventive medical care services. [ABSTRACT FROM AUTHOR]

Human activities have reorganized the earth's biota resulting in spatially disparate locales becoming more or less similar in species composition over time through the processes of biotic homogenization and biotic differentiation, respectively. Despite mounting evidence suggesting that this process may be widespread in both aquatic and terrestrial systems, past studies have predominantly focused on single taxonomic groups at a single spatial scale. Furthermore, change in pairwise similarity is itself dependent on two distinct processes, spatial turnover in species composition and changes in gradients of species richness. Most past research has failed to disentangle the effect of these two mechanisms on homogenization patterns. Here, we use recent statistical advances and collate a global database of homogenization studies (20 studies, 50 datasets) to provide the first global investigation of the homogenization process across major faunal and floral groups and elucidate the relative role of changes in species richness and turnover. We found evidence of homogenization (change in similarity ranging from -- 0.02 to 0.09) across nearly all taxonomic groups, spatial extent and grain sizes. Partitioning of change in pairwise similarity shows that overall change in community similarity is driven by changes in species richness. Our results show that biotic homogenization is truly a global phenomenon and put into question many of the ecological mechanisms invoked in previous studies to explain patterns of homogenization. [ABSTRACT FROM AUTHOR]

Fibrates, activators of the nuclear receptor PPARα, improve dyslipidemia, but their effects on insulin resistance and vascular disease are unresolved. To test the hypothesis that PPARα activation improves insulin resistance and vascular function, we determined the effects of fenofibrate in healthy adults with insulin resistance induced by short-term glucocorticoid administration. Eighteen normal weight subjects were studied in four stages: at baseline, after 21 days of fenofibrate (160 mg/day) alone, after 3 days of dexamethasone (8 mg/day) added to fenofibrate, and after 3 days of dexamethasone added to placebo (dexamethasone alone). Dexamethasone alone caused hyperinsulinemia, increased glucose, decreased glucose disposal, and reduced insulin-induced suppression of hepatic glucose production as determined by hyperinsulinemic euglycemic clamp and i creased systolic blood pressure as determined by ambulatory monitoring, features associated with an insulin-resistant state. Fenofibrate improved fasting LDL and total cholesterol in the setting of dexamethasone treatment but had no significant effect on levels of insulin or glucose, insulin-stimulated glucose disposal, or insulin suppression of glucose production during clamps, or ambulatory monitored blood pressure. In the absence of dexamethasone, fenofibrate lowered fasting triglycerides and cholesterol but unexpectedly increased systolic blood pressure by ambulatory monitoring. These data suggest that PPARα activation in humans does not correct insulin resistance induced by glucocorticoids and may adversely affect blood pressure. [ABSTRACT FROM AUTHOR]

Reports on the results of an intensive investigation of arsenic-induced skin lesions in the indigenous Atacameno people of Northern Chile. Suggestions that the population might be protected from the health effects of arsenic in drinking water due to centuries of exposure; Increased susceptibility of populations with extensive malnutrition.

Competing Interests: Declarations. Ethics approval and consent to participate: All participants provided verbal consent prior to beginning the interviews. The University of Pennsylvania’s IRB approved this research (Protocol #: 850924). Competing interests: The authors declare no competing interests.

Endogenous viral elements (EVEs) are remnants of viral genetic material endogenized into the host genome. They have, in the last decades, attracted attention for their role as potential contributors to pathogenesis, drivers of selective advantage for the host, and genomic remnants of ancient viruses. EVEs have a nuanced and complex influence on both host health and evolution, and can offer insights on the deep evolutionary history of viruses. As an emerging field of research, several factors limit a comprehensive understanding of EVEs: they are currently underestimated and periodically overlooked in studies of the host genome, transcriptome, and virome. The absence of standardized guidelines for ensuring EVE-related data availability and accessibility following the FAIR ('findable, accessible, interoperable, and reusable') principles obstructs our ability to gather and connect information. Here, we discuss challenges to the availability and accessibility of EVE-related data and propose potential solutions. We identified the biological and research focus imbalance between different types of EVEs, and their overall biological complexity as genomic loci with viral ancestry, as potential challenges that can be addressed with the development of a user-oriented identification tool. In addition, reports of EVE identification are scattered between different subfields under different keywords, and EVE sequences and associated data are not properly gathered in databases. While developing an open and dedicated database might be ideal, targeted improvements of generalist databases might provide a pragmatic solution to EVE data and metadata accessibility. The implementation of these solutions, as well as the collective effort by the EVE scientific community in discussing and setting guidelines, is now drastically needed to lead the development of EVE research and offer insights into host-virus interactions and their evolutionary history., Competing Interests: None declared., (© The Author(s) 2024. Published by Oxford University Press.)

A comprehensive understanding of molecular changes during brain aging is essential to mitigate cognitive decline and delay neurodegenerative diseases. The interpretation of mRNA alterations during brain aging is influenced by the health and age of the animal cohorts studied. Here, we carefully consider these factors and provide an in-depth investigation of mRNA splicing and dynamics in the aging mouse brain, combining short- and long-read sequencing technologies with extensive bioinformatic analyses. Our findings encompass a spectrum of age-related changes, including differences in isoform usage, decreased mRNA dynamics and a module showing increased expression of neuronal genes. Notably, our results indicate a reduced abundance of mRNA isoforms leading to nonsense-mediated RNA decay and suggest a regulatory role for RNA-binding proteins, indicating that their regulation may be altered leading to the reshaping of the aged brain transcriptome. Collectively, our study highlights the importance of studying mRNA splicing events during brain aging., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Background Blood pressure ( BP ) varies over time within individual patients and across different BP measurement techniques. The effect of different BP targets on concordance between BP measurements is unknown. The goals of this analysis are to evaluate concordance between (1) clinic and ambulatory BP , (2) clinic visit-to-visit variability and ambulatory BP variability, and (3) first and second ambulatory BP and to evaluate whether different clinic targets affect these relationships. Methods and Results The SPRINT (Systolic Blood Pressure Intervention Trial) ambulatory BP monitoring ancillary study obtained ambulatory BP readings in 897 participants at the 27-month follow-up visit and obtained a second reading in 203 participants 293±84 days afterward. There was considerable lack of agreement between clinic and daytime ambulatory systolic BP with wide limits of agreement in Bland-Altman plots of -21 to 34 mm Hg in the intensive-treatment group and -26 to 32 mm Hg in the standard-treatment group. Overall, there was poor agreement between clinic visit-to-visit variability and ambulatory BP variability with correlation coefficients for systolic and diastolic BP all <0.16. We observed a high correlation between first and second ambulatory BP ; however, the limits of agreement were wide in both the intensive group (-27 to 21 mm Hg) and the standard group (-23 to 20 mm Hg). Conclusions We found low concordance in BP and BP variability between clinic and ambulatory BP and second ambulatory BP . Results did not differ by treatment arm. These results reinforce the need for multiple BP measurements before clinical decision making.

Background Niacin is a broad-spectrum lipid-modulating drug, but its mechanism of action is unclear. Genome-wide association studies have identified multiple loci associated with blood lipid levels and lipoprotein (a). It is unknown whether these loci modulate response to niacin. Methods and Results Using data from the AIM - HIGH (Atherothrombosis Intervention in Metabolic Syndrome with Low HDL /High Triglycerides and Impact on Global Health Outcomes) trial (n=2054 genotyped participants), we determined whether genetic variations at validated loci were associated with a differential change in plasma lipids and lipoprotein (a) 1 year after randomization to either statin+placebo or statin+niacin in a variant-treatment interaction model. Nominally significant interactions ( P<0.05) were found for genetic variants in MVK , LIPC , PABPC 4, AMPD 3 with change in high-density lipoprotein cholesterol; SPTLC 3 with change in low-density lipoprotein cholesterol; TOM 1 with change in total cholesterol; PDXDC 1 and CYP 26A1 with change in triglycerides; and none for lipoprotein (a). We also investigated whether these loci were associated with cardiovascular events. The risk of coronary disease related death was higher in the minor allele carriers at the LIPC locus in the placebo group (odds ratio 2.08, 95% confidence interval 1.11-3.90, P=0.02) but not observed in the niacin group (odds ratio 0.89, 95% confidence interval 0.48-1.65, P=0.7); P-interaction =0.02. There was a greater risk for acute coronary syndrome (odds ratio 1.85, 95% confidence interval 1.16-2.77, P=0.02) and revascularization events (odds ratio 1.64, 95% confidence interval 1.2-2.22, P=0.002) in major allele carriers at the CYP 26A1 locus in the placebo group not seen in the niacin group. Conclusions Genetic variation at loci previously associated with steady-state lipid levels displays evidence for lipid response to niacin treatment. Clinical Trials Registration URL: https://www.clinicaltrials.gov . Unique identifier: NCT00120289.

Traumatic brain injury (TBI) disrupts brain communication and increases risk for post-traumatic stress disorder (PTSD). However, mechanisms by which TBI-related disruption of brain communication confers PTSD risk have not been successfully elucidated in humans. This may be in part because functional MRI (fMRI), the most common technique for measuring functional brain communication, is unreliable for characterizing individual patients. However, this unreliability can be overcome with sufficient within-individual data. Here, we examined whether relationships could be observed among TBI, structural and functional brain connectivity, and PTSD severity by collecting ∼3.5 hours of resting-state fMRI and diffusion tensor imaging (DTI) data in each of 26 United States military veterans. We observed that a TBI history was associated with decreased whole-brain resting-state functional connectivity (RSFC), while the number of lifetime TBIs was associated with reduced whole-brain fractional anisotropy (FA). Both RSFC and FA explained independent variance in PTSD severity, with RSFC mediating the TBI-PTSD relationship. Finally, we showed that large amounts of per-individual data produced highly reliable RSFC measures, and that relationships among TBI, RSFC/FA, and PTSD could not be observed with typical data quantities. These results demonstrate links among TBI, brain connectivity, and PTSD severity, and illustrate the need for precise characterization of individual patients using high-data fMRI scanning.

Background: The current US HIV treatment guidelines support initiation of antiretroviral therapy (ART) for persons with HIV for personal health benefits and prevention of HIV transmission. However, high levels of adherence to ART are critical to maximize individual and public health benefits. We examined the nonclinical barriers to ART initiation for clinically eligible individuals and the provider- and patient-related factors associated with these barriers among HIV-infected patients in Houston/Harris County, Texas., Methods: We analyzed data obtained from a probability sample of HIV medical care providers (HMCPs) in 13 outpatient facilities in Houston/Harris County, Texas surveyed between June and September 2009. We used an inductive thematic approach to code HMCP responses to an open-ended question that asked the main reasons why providers may delay initiating ART for clinically eligible patients., Results: The reasons cited by providers for delaying ART for clinically eligible patients were adherence (42.5%; 95% confidence interval [CI]: 28.5-57.8), acceptance (30%; 95% CI: 18.1-45.4), and structural concerns (27.5%; 95% CI: 16.1-42.8), with significant variations ( P < .0001) noted across patients' race/ethnicity and transmission category. HIV medical care providers with 6 to 10 years' experience in HIV care and those providing medical care for more than 100 patients monthly were about 4 times (adjusted odds ratio [aOR]: 3.80; 95% CI: 1.20-5.92; P = .039) and 10 times (aOR: 10.36; 95% CI: 1.42-22.70; P = .019) more likely to state adherence and acceptance concerns, respectively, as reasons for delaying ART for clinically eligible patients., Conclusion: Our findings highlight the fact that clinical guidelines are only a starting point for medical decision-making process and that patients themselves play an important role. HMCP access to referrals for other medical issues, support services, and treatment education may help improve adherence and patient readiness for ART, thereby avoiding systemic delays.

Background: Depression following acute coronary syndrome (ACS) constitutes a serious and debilitating problem. Approximately one in five patients will develop significant depression following ACS and less severe depressive symptoms are even more frequent. Furthermore, anxiety symptoms and sleep-wake disturbances are frequent. The objective of the MEDACIS trial is to investigate whether prophylactic treatment with melatonin has a preventive effect on depression, depressive and anxiety symptoms, sleep, and circadian disturbances following ACS., Methods/design: "The effect of MElatonin and Depressive symptoms, Anxiety, CIrcadian and Sleep disturbances in patients after acute coronary syndrome" trial (MEDACIS) is a multicenter, double-blinded, placebo-controlled, randomized clinical trial. A total of 240 patients with ACS and no depressive symptoms will be included in the trial for treatment with either 25 mg melatonin or placebo for a 12-week period. Development and severity of depressive symptoms will be evaluated using Major Depression Inventory every 2 weeks with the purpose of investigating the potential preventive effect of melatonin on depressive symptoms., Discussion: Previously, only selective serotonin reuptake inhibitors (SSRIs) have been investigated in a primary preventive setup in patients following ACS. However, SSRIs are associated with several side effects. An ideal intervention would constitute the highest degree of prevention of depressive symptoms with the lowest risk of side effects. In this regard, melatonin may have advantages due to its low toxicity as well as its proven anxiolytic and hypnotic effects., Trial Registration: ClinicalTrials.gov, Identifier: NCT02451293 . Registered on 12 May 2015. EudraCT nr. 2015-002116-32.

Magnetic resonance imaging data were acquired at ∼24 h and ∼3 months post-injury on mild traumatic brain injury (mTBI; n = 75) and orthopedic injury (n = 60) cohorts. The mTBI subjects were randomly assigned to a treatment group with atorvastatin or a non-treatment mTBI group. The treatment group was further divided into drug and placebo subgroups. FreeSurfer software package was used to compute cortical thickness based on the three dimensional T1-weighted images at both time-points. Cross-sectional analysis was carried out to compare cortical thickness between the mTBI and control groups. Longitudinal unbiased templates were generated for all subjects and cortical thickness measurements were compared between baseline and follow-up scans in the mTBI group. At baseline, significant reduction in cortical thickness was observed in the left middle temporal and the right superior parietal regions in the mTBI group, relative to the control group (p = 0.01). At follow-up, significant cortical thinning was again observed in the left middle temporal cortex in the mTBI group. Further analysis revealed significant cortical thinning only in the non-treatment group relative to the control group. In the follow-up, small regions with significant but subtle cortical thinning and thickening were seen in the frontal, temporal, and parietal lobes in the left hemisphere in the non-treatment group only. Our results indicate that cortical thickness could serve as a useful measure in identifying subtle changes in mTBI patients., Competing Interests: Author Disclosure Statement No competing financial interests exist.

Big brown bats ( Eptesicus fuscus ) overwintering outside the underground environment are not believed to play a role in the epidemiology of the disease white-nose syndrome (WNS), caused by the fungus Pseudogymnoascus destructans (Pd). Using quantitative real-time PCR (qPCR), we provide molecular evidence for Pd on four big brown bats overwintering in heated buildings in New Brunswick, Canada. Two of the affected individuals also had very mild, focal, pustular, fungal dermatitis identified microscopically. A third bat, which was qPCR Pd-negative, had similar fungal lesions. Despite determining that these fungal lesions were caused by a suspected ascomycete, the intralesional fungi were not confirmed to be Pd. These findings demonstrate that bats overwintering in heated buildings and other above-ground sites may have subclinical or preclinical WNS, or be contaminated with Pd, and could play a role in local dispersal of Pd. Our inability to determine if the ascomycetes causing pustular lesions were Pd highlights the need for ancillary diagnostic tests, such as in situ hybridization or immunohistochemistry, so that Pd can be detected directly within a lesion. As the host-pathogen relationship for Pd evolves, and where bat species are exposed to the fungus under varying temperature regimes, lesions may become less stereotypic and such tests could help define these changes.

Aims: The role of craving for alcohol as a response to alcohol treatment is not well understood. We examined daily diary ratings of craving over the course of 28 days among individuals participating in an inpatient substance abuse treatment program., Methods: Participants were alcohol dependent patients (n = 100) in the Hazelden residential treatment program who were offered and agreed to take naltrexone and an age- and gender-matched comparison group (n = 100) of alcohol-dependent patients in the same program who declined the offer of treatment with naltrexone. Changes in craving over time were compared between the two groups., Results: The naltrexone-treated group reported a more rapid decrease in craving than the usual care group., Conclusions: The change in the trajectory of craving is consistent with prior reports suggesting that craving reduction is a mechanism of naltrexone's efficacy in treating alcohol dependence. Providing naltrexone to individuals seeking treatment for alcohol dependence may accelerate a reduction in their craving, consistent with a primary target of many addiction treatment programs., Short Summary: Craving ratings by 100 residential patients taking naltrexone for alcohol dependence were compared to ratings by 100 patients who did not take naltrexone. Craving for alcohol decreased more rapidly in the patients taking naltrexone. Providing naltrexone to individuals seeking treatment for alcohol dependence may accelerate a reduction in craving, which may benefit treatment efforts., (© The Author 2016. Medical Council on Alcohol and Oxford University Press. All rights reserved.)

Background: Stereotactic body radiation therapy (SBRT) is considered the standard treatment for medically inoperable early stage lung cancer. Bronchoscopy has shown to be effective in obtaining diagnosis of peripheral lung tumors, staging the mediastinum (with endobronchial ultrasound- EBUS-), and placing fiducial markers (FMs). However, the combination of these 3 procedures in a single bronchoscopy has not been studied. The aim of this study is to describe safety and feasibility of performing diagnosis, systematic nodal staging, and placement of FMs in a single bronchoscopic procedure., Methods: Retrospective review of patients who underwent bronchoscopy with diagnosis of peripheral lung cancer, EBUS for nodal staging, and FM placement in a single procedure at Michael E. DeBakey VA Medical Center between January 2011 and July 2015., Results: Twenty-one patients met our criteria, one having 2 synchronous tumors. 95% of patients had an ASA score of at least 3. Twenty-two tumors were diagnosed with a size of 2.72±1.06 cm. Distance from pleura was 1.33±1.42 cm. Median duration of bronchoscopy was 96 minutes (range, 75 to 136 minutes). Guided-bronchoscopy provided diagnosis of lung cancer in all cases. Fluoroscopy and RP-EBUS were utilized in 21 patients, "hybrid" scope in 14, and electromagnetic navigational bronchoscopy in 3. A total of 100 lymph nodes (LN) were sampled with EBUS-TBNA, with 95% of the patients having at least 4 LN sampled. A total of 71 FM were placed for 22 tumors. All markers were retained and allowed for successful SBRT. There were no pneumothoraces and no major complications., Conclusions: Although it results in lengthy procedures, a single bronchoscopy obtaining diagnosis of peripheral lung nodules, systematic nodal staging, and FM placement can be safely performed in high-risk patients. Our "all-in-one" strategy could potentially expedite treatment, decrease complications, and reduce costs. Further prospective studies are needed to corroborate our findings.

Although most patients with mild traumatic brain injury (mTBI) recover within 3 months, a subgroup of patients experience persistent symptoms. Yet, the prevalence and predictors of persistent dysfunction in patients with mTBI remain poorly understood. In a longitudinal study, we evaluated predictors of symptomatic and cognitive dysfunction in adolescents and young adults with mTBI, compared with two control groups-patients with orthopedic injuries and healthy uninjured individuals. Outcomes were assessed at 3 months post-injury. Poor symptomatic outcome was defined as exhibiting a symptom score higher than 90% of the orthopedic control (OC) group, and poor cognitive outcome was defined as exhibiting cognitive performance poorer than 90% of the OC group. At 3 months post-injury, more than half of the patients with mTBI (52%) exhibited persistently elevated symptoms, and more than a third (36.4%) exhibited poor cognitive outcome. The rate of high symptom report in mTBI was markedly greater than that of typically developing (13%) and OC (17%) groups; the proportion of those with poor cognitive performance in the mTBI group exceeded that of typically developing controls (15.8%), but was similar to that of the OC group (34.9%). Older age at injury, female sex, and acute symptom report were predictors of poor symptomatic outcome at 3 months. Socioeconomic status was the only significant predictor of poor cognitive outcome at 3 months.

The biologically and geologically extremely diverse archipelagos of Wallacea, Australasia and Oceania have long stimulated ecologists and evolutionary biologists. Yet, few molecular phylogenetic analyses of the terrestrial fauna have been carried out to understand the evolutionary patterns. We use dense taxon and character sampling of more than 7000 bp DNA sequence data for a group of diving beetles ranging from the Holarctic throughout Asia to as far east as French Polynesia. We here show that an ecologically diverse, common and widespread (Portugal to New Zealand) arthropod supertramp species originated in the highlands of New Guinea, ca 6.0-2.7 Myr ago. The approximately 25 closely related species are narrow endemics in Australasia/Oceania. The ancestor of this clade colonized that region from Eurasia ca 9-7 Myr ago. Our finding contradicts the widely held view of local endemism as an evolutionary dead end, as we find multiple peripatric speciation events within the Pleistocene and complex colonization patterns between the Oriental and Australian zoogeographic regions, including the recolonization of Eurasia, jumping across Wallace's line and colonization of continental Australia out of New Guinea. Our study strongly highlights the importance of dispersal over water gaps in shaping biogeographic patterns.

Objective: To describe the course and predictors of glycemic control among patients with type 2 diabetes after sulfonylureas (SUs) are added to metformin (MF)., Research Design and Methods: Patients (n = 2,220) treated with MF monotherapy for >90 days before initiating MF plus SU combination therapy between January 1998 and March 2004 were studied in a retrospective analysis of electronic medical records from U.K. primary care practices using the General Practice Research Database. Median glycoslyated hemoglobin A(1c) (A1C) before and after SU initiation was described, and patient characteristics were evaluated as predictors of time until A1C > or =8.0% or glucose-lowering therapy was intensified (by starting insulin or adding a third oral agent)., Results: At 6 months post-SU initiation, median A1C resumed deteriorating at a somewhat comparable rate to that observed on MF monotherapy. Higher pre-SU A1C, younger age, female sex, shorter diabetes duration, higher serum creatinine, and being an ex-smoker predicted time until A1C > or =8.0% or glucose-lowering therapy was intensified in various analyses. Median A1C was 9.5% when therapy was intensified. A1C > or =8.0% was estimated to occur in 85% of patients 4 years after SU initiation and in 68% 4 years after initially achieving A1C <7% on MF plus SU therapy., Conclusions: In this population, glycemic control is improved following the addition of SUs to MF, but deterioration resumes as early as 6 months. The high proportion of patients remaining on MF plus SU therapy despite having A1C > or =8.0% suggests that there are significant barriers to starting insulin or adding a third agent when treatment goals are not achieved with this combination.