It has previously been thought that there was a steep Cretaceous and Cenozoic radiation of marine invertebrates. This pattern can be replicated with a new data set of fossil occurrences representing ...3.5 million specimens, but only when older analytical protocols are used. Moreover, analyses that employ sampling standardization and more robust counting methods show a modest rise in diversity with no clear trend after the mid-Cretaceous. Globally, locally, and at both high and low latitudes, diversity was less than twice as high in the Neogene as in the mid-Paleozoic. The ratio of global to local richness has changed little, and a latitudinal diversity gradient was present in the early Paleozoic.
1. Litter decomposition recycles nutrients and causes large fluxes of carbon dioxide into the atmosphere. It is typically assumed that climate, litter quality and decomposer communities determine ...litter decay rates, yet few comparative studies have examined their relative contributions in tropical forests. 2. We used a short-term litterbag experiment to quantify the effects of litter quality, placement and mesofaunal exclusion on decomposition in 23 tropical forests in 14 countries. Annual precipitation varied among sites (760-5797 mm). At each site, two standard substrates (Raphia farinifera and Laurus nobilis) were decomposed in fine- and coarse-mesh litterbags both above and below ground for approximately 1 year. 3. Decomposition was rapid, with >95% mass loss within a year at most sites. Litter quality, placement and mesofaunal exclusion all independently affected decomposition, but the magnitude depended upon site. Both the average decomposition rate at each site and the ratio of above- to below-ground decay increased linearly with annual precipitation, explaining 60-65% of among-site variation. Excluding mesofauna had the largest impact on decomposition, reducing decomposition rates by half on average, but the magnitude of decrease was largely independent of climate. This suggests that the decomposer community might play an important role in explaining patterns of decomposition among sites. Which litter type decomposed fastest varied by site, but was not related to climate. 4. Synthesis. A key goal of ecology is to identify general patterns across ecological communities, as well as relevant site-specific details to understand local dynamics. Our pan-tropical study shows that certain aspects of decomposition, including average decomposition rates and the ratio of above- to below-ground decomposition are highly correlated with a simple climatic index: mean annual precipitation. However, we found no relationship between precipitation and effects of mesofaunal exclusion or litter type, suggesting that site-specific details may also be required to understand how these factors affect decomposition at local scales.
Pheochromocytomas are neural crest-derived tumors that arise from inherited or sporadic mutations in at least six independent genes. The proteins encoded by these multiple genes regulate distinct ...functions. We show here a functional link between tumors with VHL mutations and those with disruption of the genes encoding for succinate dehydrogenase (SDH) subunits B (SDHB) and D (SDHD). A transcription profile of reduced oxidoreductase is detected in all three of these tumor types, together with an angiogenesis/hypoxia profile typical of VHL dysfunction. The oxidoreductase defect, not previously detected in VHL-null tumors, is explained by suppression of the SDHB protein, a component of mitochondrial complex II. The decrease in SDHB is also noted in tumors with SDHD mutations. Gain-of-function and loss-of-function analyses show that the link between hypoxia signals (via VHL) and mitochondrial signals (via SDH) is mediated by HIF1 alpha . These findings explain the shared features of pheochromocytomas with VHL and SDH mutations and suggest an additional mechanism for increased HIF1 alpha activity in tumors.
Two patients experienced compression of a coronary artery bypass graft or native coronary artery by mediastinal drains placed after cardiac surgery. Both events were identified in the catheterization ...laboratory and resolved after removal of the drains. One patient required concomitant percutaneous thrombectomy of the bypass graft. Although both patients' cardiac function was initially severely impaired, neither patient had permanent cardiac damage and both were successfully discharged home.
To evaluate associations of mood, anxiety, stress-/trauma-related, and psychotic disorders, both treated and untreated, with duration of unsuppressed HIV viral load (VL) among persons living with HIV ...(PLWH).
The DC Cohort, an observational clinical cohort of PLWH followed from 2011 to 2018 at 14 sites in Washington, DC.
Among PLWH ≥18 years old who received primary care at their HIV clinic, we determined in a time-updated manner whether participants had diagnoses and pharmacologic prescriptions for mood, anxiety, stress-/trauma-related, and/or psychotic disorders. Associations between psychiatric disorders/treatments and the proportion of subsequent days with VL ≥200 copies/mL were assessed using multivariable Poisson regression with generalized estimating equations.
Among 5904 participants (median age 51; 70% men; 82% Black), 45% had ≥1 psychiatric disorder, including 38% with mood disorders (50% treated), 18% with anxiety or stress-/trauma-related disorders (64% treated), and 4% with psychotic disorders (52% treated). Untreated major depressive disorder (adjusted rate ratio = 1.17; 95% confidence interval: 1.00 to 1.37), untreated other/unspecified depressive disorder (1.23; 1.01 to 1.49), untreated bipolar disorder (1.39; 1.15 to 1.69), and treated bipolar disorder (1.25; 1.02 to 1.53) (vs. no mood disorder) predicted more time with VL ≥200 copies/mL. Treated anxiety disorders (vs. no anxiety disorder) predicted less time (0.78; 0.62 to 0.99). Associations were weaker and nonsignificant for treated depressive disorders (vs. no mood disorder) and untreated anxiety disorders (vs. no anxiety disorder).
PLWH with depressive and bipolar disorders, particularly when untreated, spent more time with unsuppressed VL than PLWH without a mood disorder. Treatment of mood disorders may be important for promoting sustained viral suppression.
Statin coverage has been examined among HIV-infected patients using Adult Treatment Panel III (ATP III) and American College of Cardiology/American Heart Association (ACC/AHA) guidelines, although ...not with newer National Lipid Association (NLA) guidelines. We investigated statin eligibility, prescribing practices, and therapeutic responses using these three guidelines. Sociodemographic, clinical, and laboratory data were collected between 2011 and 2016 for HIV-infected outpatients enrolled in the DC Cohort, a multi-center, prospective, observational study in Washington, DC. This analysis included patients aged ≥21 years receiving primary care at their HIV clinic site with ≥1 cholesterol result available. Of 3312 patients (median age 52; 79% black), 52% were eligible for statins based on ≥1 guideline, including 45% (NLA), 40% (ACC/AHA), and 30% (ATP III). Using each guideline, 49% (NLA), 56% (ACC/AHA), and 73% (ATP III) of eligible patients were prescribed statins. Predictors of new prescriptions included older age (aHR = 1.16 1.08-1.26/5 years), body mass index ≥30 (aHR = 1.50 1.07-2.11), and diabetes (aHR = 1.35 1.03-1.79). Hepatitis C coinfection was inversely associated with statin prescriptions (aHR = 0.67 0.45-1.00). Among 216 patients with available cholesterol results pre-/post-prescription, 53% achieved their NLA cholesterol goal after 6 months. Hepatitis C coinfection was positively associated (aHR = 1.87 1.06-3.32), and depression (aHR = 0.56 0.35-0.92) and protease inhibitor use (aHR = 0.61 0.40-0.93) were inversely associated, with NLA goal achievement. Half of patients were eligible for statins based on current US guidelines, with the highest proportion eligible based on NLA guidelines, yet, fewer received prescriptions and achieved treatment goals. Greater compliance with recommended statin prescribing practices may reduce cardiovascular disease risk among HIV-infected individuals.
To explore reasons for the disproportionate metabolic and cardiovascular disease burdens among older HIV-infected persons, we investigated whether associations of CD4 count and HIV viral load (VL) ...with non-high-density lipoprotein cholesterol (non-HDL-C) and high-density lipoprotein cholesterol HDL-C differed by age. Longitudinal clinical and laboratory data were collected between 2011 and 2016 for HIV-infected outpatients in the DC Cohort study. Using data for patients aged ≥21 years with ≥1 cholesterol result and contemporaneous CD4/VL results, we created multivariable linear regression models with generalized estimating equations. Among 3,912 patients, the median age was 50 years, 78% were male, 76% were non-Hispanic black, 93% were using antiretroviral therapy, 8% had a CD4 count <200 cells/μL, and 18% had an HIV VL ≥200 copies/mL. Overall, CD4 count <200 (vs. >500) cells/μL and VL ≥200 copies/mL were associated with lower non-HDL-C concentrations (p < .01), but associations were more positive with increasing age (CD4-age/VL-age interactions, p < .01). CD4 count <200 cells/μL was associated with lower non-HDL-C among patients aged <50 years β = -7.8 mg/dL (95% confidence interval, CI: -13.2 to -2.4) but higher non-HDL-C among patients aged 60-69 years β = +8.1 mg/dL (95% CI: 0.02-16.2). VL ≥200 copies/mL was associated with lower non-HDL-C among patients aged <50 years β = -3.3 mg/dL (95% CI: -6.7 to 0.1) but higher non-HDL-C among patients aged ≥70 years β = +16.0 mg/dL (95% CI: -1.4 to 33.3), although precision was reduced in age-stratified analyses. Although no age differences were detected for HDL-C, VL ≥200 copies/mL was more strongly associated with lower HDL-C concentrations when CD4 count was <200 cells/μL β = -7.0 mg/dL (95% CI: -9.7 to -4.3) versus 200-500 cells/μL β = -4.2 (95% CI: -5.9 to -2.6) or >500 cells/μL β = -2.2 (95% CI: -3.7 to -0.8) (CD4-VL interaction, p < .01). We detected a novel age-modified relationship between immunosuppression and viremia and atherogenic cholesterol patterns. These findings may contribute to our understanding of the high risk of dyslipidemia observed among persons aging with HIV.
Abstract
We conducted a retrospective analysis of 38 children and youth with human immunodeficiency virus (aged 0–19 years) in the United States and report an increased rate of change of BMI-for-age ...z score after initiating integrase strand transfer inhibitors (+0.19 z score units/year 95% confidence interval, .01–.37; P = .036) for a median follow-up of 527.5 days.
Children and youth with HIV in the United States (n=38) have an increased rate of change of BMI-for-age z-score (+0.19 z-score units/year) after initiating integrase strand transfer inhibitors for a median follow-up of 527.5 days.
Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is characterized by respiratory distress, multiorgan dysfunction, and, in some cases, ...death. The pathological mechanisms underlying COVID-19 respiratory distress and the interplay with aggravating risk factors have not been fully defined. Lung autopsy samples from 18 patients with fatal COVID-19, with symptom onset-to-death times ranging from 3 to 47 days, and antemortem plasma samples from 6 of these cases were evaluated using deep sequencing of SARS-CoV-2 RNA, multiplex plasma protein measurements, and pulmonary gene expression and imaging analyses. Prominent histopathological features in this case series included progressive diffuse alveolar damage with excessive thrombosis and late-onset pulmonary tissue and vascular remodeling. Acute damage at the alveolar-capillary barrier was characterized by the loss of surfactant protein expression with injury to alveolar epithelial cells, endothelial cells, respiratory epithelial basal cells, and defective tissue repair processes. Other key findings included impaired clot fibrinolysis with increased concentrations of plasma and lung plasminogen activator inhibitor-1 and modulation of cellular senescence markers, including p21 and sirtuin-1, in both lung epithelial and endothelial cells. Together, these findings further define the molecular pathological features underlying the pulmonary response to SARS-CoV-2 infection and provide important insights into signaling pathways that may be amenable to therapeutic intervention.
Abstract
Integrase inhibitors (INSTIs) are recommended by expert panels as initial therapy for people with HIV. Because there can be disparities in prescribing and uptake of novel and/or recommended ...therapies, this analysis assessed potential INSTI prescribing disparities using a combined data set from the Johns Hopkins HIV Clinical Cohort and the DC Cohort. We performed multivariable logistic regression to identify factors associated with ever being prescribed an INSTI. Disparities were noted, including clinic location, age, and being transgender. Identifying disparities may allow clinicians to focus their attention on these individuals and ensure that therapy decisions are grounded in valid clinical reasons.
We assessed INSTI prescribing disparities using Johns Hopkins HIV Clinical Cohort/DC Cohort data. Disparities were noted, including clinic location, age, and being transgender. Clinicians should focus their attention on these individuals and make therapy decisions grounded in valid clinical reasons.
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