Morphological and molecular analysis of the toxicity of pharmaceutical-derived aquatic contaminants (PPCPs)​ in zebrafish

Pharmaceutical chemicals, a subset of pharmaceuticals and personal care products (PPCPs), are aquatic contaminants of emerging concern (CECs) that have been detected at elevated concentrations in surface water globally, entering waterways primarily through sewage discharges containing unmetabolized drugs and improper drug disposal. However, the aquatic toxicity of these contaminants, especially in complex mixtures, is poorly understood; moreover, biomarker frameworks have not been largely applied to this class of contaminants. Here, the toxicity of two cardiac-specific medications, triamterene (diuretic) and gemfibrozil (fibrate), was examined both singly and in mixture concentrations in order to better understand the toxicological implications of PPCP mixtures and develop a biomarker framework. Zebrafish embryos (hpf) were exposed to single-chemical trials as well as binary mixtures. Morphometric measurements were extracted for various toxicological endpoints (eye area, length, yolk sac size, and cardiac abnormalities) and results from mixture trials were compared to single-chemical trials using the response addition model. Follow-up qPCR was conducted to inform molecular mechanisms of toxicity and identify potential biomarker responses. Gemfibrozil elicited a dose-dependent decrease in eye area and length (developmental delay), as well as an increase in yolk sac area, suggesting possible interference with lipid metabolism pathways; likewise, increased cardiac abnormalities were observed in a dose-dependent manner, indicating potential cardiotoxicity. Triamterene induced a similar dose-dependent increase in cardiac abnormalities, suggesting possible cardiotoxicity. Additive toxic effects were observed in multiple endpoints, with potential synergism evident in yolk sac and cardiotoxicity. These trends indicate that complex mixtures of PPCPs in the environment could interact in waterways to produce increased toxic effects and highlight the need for toxicity assays to take into account the effect of complex PPCP mixtures in order to more accurately predict environmental effects. This study also points to the need for increased policy regulating the disposal of pharmaceutical waste

Concomitant presentation of carpal tunnel syndrome and trigger finger

<p>Abstract</p> <p>Background</p> <p>Carpal tunnel syndrome (CTS) and trigger finger (TF) are common conditions that may occur in the same patient. The etiology of most cases is unknown. The purpose of this study was to evaluate the rate of concomitant occurrence of these two conditions at presentation and to compare the concomitant occurrence in normal and diabetic patients.</p> <p>Methods</p> <p>One-hundred and eight consecutive subjects presenting to our hand clinic with CTS and/or TF were evaluated. The existence of both of these conditions was documented through a standard history and physical examination. The definition of trigger finger was determined by tenderness over the A1 pulley, catching, clicking or locking. CTS was defined in the presence of at least two of the following: numbness and tingling in a median nerve distribution, motor and sensory nerve loss (median nerve), a positive Tinel's or Phalen's test and positive electrophysiologic studies.</p> <p>Results</p> <p>The average age of the participants was 62.2 ± 13.6 years. Sixty-seven patients presented with symptoms and signs of CTS (62%), 41 (38%) subjects with signs and symptoms of TF. Following further evaluation, 66 patients (61%) had evidence of concomitant CTS and TF. Fifty-seven patients (53% of all study patients) had diabetes. The rate of subjects with diabetes was similar among the groups (p = 0.8, Chi-square test).</p> <p>Conclusion</p> <p>CTS and TF commonly occur together at presentation though the symptoms of one condition will be more prominent. Our results support a common local mechanism that may be unrelated to the presence of diabetes. We recommend evaluation for both conditions at the time of presentation.</p

Slow Diffeomorphisms of a Manifold with Two Dimensions Torus Action

The uniform norm of the differential of the n-th iteration of a diffeomorphism is called the growth sequence of the diffeomorphism. In this paper we show that there is no lower universal growth bound for volume preserving diffeomorphisms on manifolds with an effective two dimensions torus action by constructing a set of volume-preserving diffeomorphisms with arbitrarily slow growth.Comment: 12 p

Effect of a Fruit and Vegetable Prescription Program on Children's Fruit and Vegetable Consumption.

IntroductionMost children in families with low income do not meet dietary guidance on fruit and vegetable consumption. Fruit and vegetable prescription programs improve access to and affordability of health-supporting foods for adults, but their effect on dietary behavior among children is not known. The objective of this study was to describe the extent to which exposure to a fruit and vegetable prescription program was associated with changes in consumption among participants aged 2 to 18.MethodsWe used data from a modified National Cancer Institute screener to calculate fruit and vegetable intake among 883 children who were overweight or had obesity and participated in a 4- to 6-month fruit and vegetable prescription program at federally qualified health centers during 4 years (2012-2015). Secondary analyses in 2017 included paired t tests to compare change in fruit and vegetable consumption (cups/day) between first and last visits and multivariable linear regressions, including propensity dose-adjusted models, to model this change as a function of sociodemographic and program-specific covariates, such as number of clinical visits and value of prescription redemption.ResultsWe found a dose propensity-adjusted increase of 0.32 cups (95% confidence interval, 0.19-0.45 cups) for each additional visit while holding constant the predicted number of visits and site. An equal portion of the change-score increase was attributed to vegetable consumption and fruit consumption (β = 0.16 for each).ConclusionFruit and vegetable prescription programs in clinical settings may increase fruit and vegetable consumption among children in low-income households. Future research should use a comparison group and consider including qualitative analysis of site-specific barriers and facilitators to success

Siting a Low-Level Radioactive Waste Disposal Facility in Texas Volume Four- Geologic and Hydrologic Investigations of State of Texas and University of Texas Lands

The Bureau of Economic Geology, The University of Texas at Austin, conducted preliminary investigations of the geology and hydrology of 5 areas in Culberson and Hudspeth Counties, Texas, selected by the Texas Low-Level Radioactive Waste Disposal Authority as potential sites for a low-level radioactive waste repository. This report discusses the results of those studies. Two areas in Culberson County, Texas, Site S-15 and Block 46 and adjacent regions, were investigated. The Permian Castile Formation underlies all of Site S-15 and the eastern half of Block 46. The Castile Formation displays evidence of extensive solution and local collapse and appears to contain a complex system of karst features and underground solution channels. The western half of Block 46 is underlain by the Permian Bell Canyon Formation, consisting of interbeds of sandstone and limestone. Both the Castile and subjacent Bell Canyon Formations contain prominent joint systems and local areas of normal faults. Surficial deposits are commonly composed of detritus derived from local formations and appear to be both porous and permeable. The groundwater flow in both areas is governed by karst dissolution and collapse features. The chemical and isotopic composition of groundwater indicates active recharge through the thin unsaturated zone combined with older water flowing from the west. Residence time of groundwater in the aquifers is relatively short, and numerous springs discharge from the shallow groundwater table.Bureau of Economic Geolog

Social Determinants of Health: Underreported Heterogeneity in Systematic Reviews of Caregiver Interventions.

BACKGROUND AND OBJECTIVES:Although most people have some experience as caregivers, the nature and context of care are highly variable. Caregiving, socioeconomic factors, and health are all interrelated. For these reasons, caregiver interventions must consider these factors. This review examines the degree to which caregiver intervention research has reported and considered social determinants of health. RESEARCH DESIGN AND METHODS:We examined published systematic reviews and meta-analyses of interventions for older adults with age-related chronic conditions using the PRISMA and AMSTAR 2 checklists. From 2,707 papers meeting search criteria, we identified 197 potentially relevant systematic reviews, and selected 33 for the final analysis. RESULTS:We found scant information on the inclusion of social determinants; the papers lacked specificity regarding race/ethnicity, gender, sexual identity, socioeconomic status, and geographic location. The majority of studies focused on dementia, with other conditions common in later life vastly underrepresented. DISCUSSION AND IMPLICATIONS:Significant gaps in evidence persist, particularly for interventions targeting diverse conditions and populations. To advance health equity and improve the effectiveness of interventions, research should address caregiver heterogeneity and improve assessment, support, and instruction for diverse populations. Research must identify aspects of heterogeneity that matter in intervention design, while recognizing opportunities for common elements and strategies

Bilateral visual loss due to a giant olfactory meningioma

Olfactory groove meningiomas can present as large and insidious masses in the anterior cranial base. Due to their location and minimal clinical symptoms, these tumors can go undetected until they have grown extremely large. We present a clinical case and discuss the surgical management of a 63-year-old man who presented for an initial eye examination with bilateral visual loss for over 2 years due to a giant olfactory meningioma encompassing his entire frontal lobe and compressing on his optic nerves

Association Between APOL1 Genotypes and Risk of Cardiovascular Disease in MESA (Multi-Ethnic Study of Atherosclerosis).

BACKGROUND:APOL1 genetic variants confer an increased risk for kidney disease. Their associations with cardiovascular disease (CVD) are less certain. We aimed to compare the prevalence of subclinical CVD and incidence of atherosclerotic CVD and heart failure by APOL1 genotypes among self-identified black participants of MESA (Multi-Ethnic Study of Atherosclerosis). METHODS AND RESULTS:Cross-sectional associations of APOL1 genotypes (high-risk=2 alleles; low-risk=0 or 1 allele) with coronary artery calcification, carotid-intimal media thickness, and left ventricular mass were evaluated using logistic and linear regression. Longitudinal associations of APOL1 genotypes with incident myocardial infarction, stroke, coronary heart disease, and congestive heart failure were examined using Cox regression. We adjusted for African ancestry, age, and sex. We also evaluated whether hypertension or kidney function markers explained the observed associations. Among 1746 participants with APOL1 genotyping (mean age 62&nbsp;years, 55% women, mean cystatin C-based estimated glomerular filtration rate 89&nbsp;mL/min per 1.73&nbsp;m2, 12% with albuminuria), 12% had the high-risk genotypes. We found no difference in prevalence or severity of coronary artery calcification, carotid-intimal media thickness, or left ventricular mass by APOL1 genotypes. The APOL1 high-risk group was 82% more likely to develop incident heart failure compared with the low-risk group (95% confidence interval, 1.01-3.28). Adjusting for hypertension (hazard ratio, 1.80; 95% confidence interval, 1.00-3.24) but not markers of kidney function (hazard ratio, 1.86; 95% confidence interval, 1.03-3.35) slightly attenuated this association. The APOL1 high-risk genotypes were not significantly associated with other clinical CVD outcomes. CONCLUSIONS:Among blacks without baseline CVD, the APOL1 high-risk variants may be associated with increased risk for incident heart failure but not subclinical CVD or incident clinical atherosclerotic CVD

Políticas de cambio climático en Costa Rica, integrando esfuerzos para asumir los retos

Ante el fenómeno de cambio climático, que muchos consideran el mayor reto que la humanidad ha enfrentado, las políticas públicas son cruciales. Con el fin de establecer la capacidad de Costa Rica para alcanzar los objetivos de la Estrategia Nacional de Cambio Climático, se efectúa un análisis de las políticas públicas nacionales. Se hace una ubicación general de la normativa e iniciativas internacionales para abordar el fenómeno de cambio climático, destacando la falta de concreción de instrumentos efectivos para atacar este problema. Por otra parte, se define y describe el fenómeno climático y el calentamiento global que lleva al cambio climático

Isoform-specific subcellular localization and function of protein kinase A identified by mosaic imaging of mouse brain.

Protein kinase A (PKA) plays critical roles in neuronal function that are mediated by different regulatory (R) subunits. Deficiency in either the RIβ or the RIIβ subunit results in distinct neuronal phenotypes. Although RIβ contributes to synaptic plasticity, it is the least studied isoform. Using isoform-specific antibodies, we generated high-resolution large-scale immunohistochemical mosaic images of mouse brain that provided global views of several brain regions, including the hippocampus and cerebellum. The isoforms concentrate in discrete brain regions, and we were able to zoom-in to show distinct patterns of subcellular localization. RIβ is enriched in dendrites and co-localizes with MAP2, whereas RIIβ is concentrated in axons. Using correlated light and electron microscopy, we confirmed the mitochondrial and nuclear localization of RIβ in cultured neurons. To show the functional significance of nuclear localization, we demonstrated that downregulation of RIβ, but not of RIIβ, decreased CREB phosphorylation. Our study reveals how PKA isoform specificity is defined by precise localization