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Background: Multiparametric magnetic resonance imaging (mpMRI) may allow patients with prostate cancer (PC) on active surveillance (AS) to avoid repeat prostate biopsies during monitoring. Objective: To assess the ability of mpMRI to reduce guideline-mandated biopsy and to predict grade group upgrading in patients with International Society of Urological Pathology grade group (GG) 1 or GG 2 PC using Prostate Cancer Radiological Estimation of Change in Sequential Evaluation (PRECISE) scores. The hypothesis was that the AS disqualification rate (ASDQ) rate could be reduced to 15%. Design, setting and participants: PROMM-AS was a prospective study assessing 2-yr outcomes for an mpMRI-guided AS protocol. A 12 mo after AS inclusion on the basis of MRI/transrectal ultrasound fusion-guided biopsy (FBx), all patients underwent mpMRI. For patients with stable mpMRI (PRECISE 1–3), repeat biopsy was deferred and follow-up mpMRI was scheduled for 12 mo later. Patients with mpMRI progression (PRECISE 4–5) underwent FBx. At the end of the study, follow-up FBx was indicated for all patients. Outcome measurements and statistical analysis: We calculated the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for upgrading to GG 2 in the GG 1 group, and to GG 3 in the GG 2 group on MRI. We performed regression analyses that included clinical variables. Results and limitations: The study included 101 patients with PC (60 GG 1 and 41 GG 2). Histopathological progression occurred in 31 patients, 18 in the GG 1 group and 13 in the GG 2 group. Thus, the aim of reducing the ASDQ rate to 15% was not achieved. The sensitivity, specificity, PPV, and NPV for PRECISE scoring of MRI were 94%, 64%, 81%, and 88% in the GG 1 group, and 92%, 50%, 92%, and 50%, respectively, in the GG 2 group. On regression analysis, initial prostate-specific antigen (p

Meloxicam is a non-steroidal anti-inflammatory in the oxicam group. It has been extensively used in human and veterinary medicine for their anti-inflammatory, analgesic and antipyretic activities. Meloxicam has shown high therapeutic potential for disorders such as osteoarthritis, musculoskeletal disorder, acute respiratory infection, puerperal septicemia, mastitis and mastitis–metritis–agalactia syndrome. Although meloxicam pharmacokinetic has been described for numerous species, no paper summarizes the existing literature on this field. Thus, the aim of this review was to carry out a review of the literature on the pharmacokinetics of meloxicam in different animal species and gather the data in a single review article. A comprehensive review of the available literature in the PubMed, Web of Science and Scopus databases was performed. Meloxicam shows good bioavailability after oral and parenteral administration in most animal species (85–95%), with the lowest values in sheep after oral administration. It presents a rapid distribution with a small volume of distribution, which can be attributed to relatively high ionization state of meloxicam at physiological pH and its high plasma protein binding (close to 99%). It is extensively metabolized in the liver in several inactive polar metabolites, which are excreted, like unchanged meloxicam in urine and feces. Meloxicam also shows a long elimination half-life and low clearance.

Introduction: Gibraltar Health Authority in collaboration with Dr Terri McVeigh (Geneticist at Royal Marsden NHS Foundation Trust) have implemented a cutting-edge programme to screen for patients with certain cancer types who meet criteria for Specialist-led germline testing since January 2023. This initiative aligns with NICE guidance (DG27 and DG42), NHS Long Term Plan and NHS England National Genomic Test Directory.A - Lynch Syndrome (LS) is a hereditary condition associated with increased risk of several cancer types, including colorectal, gastrointestinal and biliary tract, genitourinary system and pancreatic cancer. It is caused by a germline pathogenic variant in one of four DNA MisMatch Repair (MMR) genes; MLH1, MSH2, MSH6 and PMS2.Approximately one in 250 individuals have Lynch Syndrome; half of whom are estimated to develop colorectal cancer.B - BRCA1 and BRCA2 are 2 important tumour-suppressor genes against breast, ovarian, prostate, pancreatic and other cancers. BRCA1 gene mutations can increase a woman's risk of developing breast cancer by the age of 70 to 65–85% and ovarian cancer to 30–50%. However, BRCA2 gene mutations can increase a woman's risk of developing breast cancer by the age of 70 to 40–85% and ovarian cancer to 10–20%. This compares to the 12.5% lifetime risk of breast cancer and 2% risk of ovarian cancer for the average British woman.Approximately one in 400 individuals are estimated to carry a BRCA1/BRCA2 mutation. Materials and methods: Tissue-based samples from biopsy or surgery are identified at weekly Oncology Multi-Disciplinary Team (MDT) meeting; based on the criteria outlined by NHS England National Genomic Test Directory.These samples are air-shipped to Royal Marsden for testing; with target Turn Around Time (TAT) of 14 days from the date of sample arrival to Clinical Genomics laboratory.Strong family history of cancer, alterations on MMR or BRCA1-2 routinely prompt referral to Dr McVeigh for consideration of germline testing. Results and discussion: At 13-month landmark, a total of 94 non-breast probands have been screened as eligible for initial testing at MDT; 89 of whom have proceeded to testing. One case was taken off programme for overseas location of tissue blocks; remaining four are planned for surgery, which will provide with further material.Excluding breast cases on this first interim analysis, 11 referrals have been sent to Dr McVeigh for germline testing: four MSI-high colon cancers; four Micro-Satellite Stable (MSS) colon cancer patients aged 40 or with family history; a co-mutation in ATM/CDK12 in prostate and two BRCA2 mutations in prostate and pancreatic cancer probands. Conclusion: From 93 non-breast probands, four colon cancers are pending conclusion on LS and two are awaiting outcome on BRCA2 mutation (prostate and pancreatic) over 30,000 Gibraltarian population; which falls well below general estimates.Counselling on individual cancer risk over life time, risk-reducing surgery, chemo-prevention, tailored screening and surveillance programmes are the main aimed benefits.Hand-in-hand liaison with Royal Marsden and Clinical Nurse Specialists have been key to implement and conduct this programme successfully.Stepped processes are being audited for Quality Improvement, care excellence, patients and caregivers' satisfaction.

Coordination of growth and division in eukaryotic cells is essential for populations of proliferating cells to maintain size homeostasis, but the underlying mechanisms that govern cell size have only been investigated in a few taxa. The green alga Chlamydomonas reinhardtii (Chlamydomonas) proliferates using a multiple fission cell cycle that involves a long G1 phase followed by a rapid series of successive S and M phases (S/M) that produces 2n daughter cells. Two control points show cell-size dependence: the Commitment control point in mid-G1 phase requires the attainment of a minimum size to enable at least one mitotic division during S/M, and the S/M control point where mother cell size governs cell division number (n), ensuring that daughter distributions are uniform. tny1 mutants pass Commitment at a smaller size than wild type and undergo extra divisions during S/M phase to produce small daughters, indicating that TNY1 functions to inhibit size-dependent cell cycle progression. TNY1 encodes a cytosolic hnRNP A-related RNA binding protein and is produced once per cell cycle during S/M phase where it is apportioned to daughter cells, and then remains at constant absolute abundance as cells grow, a property known as subscaling. Altering the dosage of TNY1 in heterozygous diploids or through mis-expression increased Commitment cell size and daughter cell size, indicating that TNY1 is a limiting factor for both size control points. Epistasis placed TNY1 function upstream of the retinoblastoma tumor suppressor complex (RBC) and one of its regulators, Cyclin-Dependent Kinase G1 (CDKG1). Moreover, CDKG1 protein and mRNA were found to over-accumulate in tny1 cells suggesting that CDKG1 may be a direct target of repression by TNY1. Our data expand the potential roles of subscaling proteins outside the nucleus and imply a control mechanism that ties TNY1 accumulation to pre-division mother cell size.

Societal Impact Statement Conserving trees is fundamental to maintaining forests, which are home to about half of the global biodiversity and provide unmeasurable benefits to people. Colombia has 5868 known species of trees, 1148 of which are endemic to the country. Unfortunately, 45% of the endemic trees of Colombia are threatened with extinction, and therefore, the ecosystem services they provide might be in jeopardy. This study represents an important contribution to conservation planning for the endemic trees of a megadiverse country and highlights critical considerations for their conservation. Summary Colombia has a very rich tree flora and high levels of tree endemism. As a contribution to the “Global Tree Assessment”, we assessed 860 species to complete the Red List of the 1148 endemic trees of the country. The information is being used to support spatial conservation planning as Key Biodiversity Areas identification. To categorize the species according to the International Union for the Conservation of Nature (IUCN) Red List guidelines, we used geographic occurrences obtained from herbarium specimens. We carried out detailed analysis of habitat quantity and quality (using forest cover and human footprint maps) and documented anthropogenic threats and conservation actions. Almost half (45%) of the endemic trees were categorized as threatened. Most species had small distributions (with an extent of occurrence of less than 40,000 km2). Endemic tree occurrences were more common in the Andes and Magdalena regions, which have very high human footprint and consequently a large proportion of threatened species. The major threat to endemic trees was habitat destruction, due mainly to deforestation for livestock and crops. Many endemic trees were present in protected areas (65%), but threatened and non‐threatened species had low coverage with habitat protection, and many of their populations persist in disturbed habitats. Colombia has hundreds of threatened endemic trees, most of them in global biodiversity hotspots, with very few proactive conservation actions. It is urgent to increase the coverage of endemic tree populations in area‐based conservation strategies and to complement this with ex situ and other conservation actions.

Menbutone is a choleretic agent currently used in Europe to treat digestive disorders in livestock and dogs. Pharmacokinetic parameters were established in 4-month Holstein calves after intravenous (IV) and intramuscular (IM) administration. The drug was administered to 12 animals (10 mg/kg) for both IV and IM routes following a crossover design. Plasma samples were collected at various time points over 24 h and analyzed by reverse-phase high-performance liquid chromatography with a photodiode-array detector, following a method validated according to European Medicines Agency guidelines. Pharmacokinetic parameters were calculated using compartmental and non-compartmental methods. Menbutone followed a two-compartment open model after IV injection, with a total clearance (Cl) of 71.9 ± 13.5 mL/h/kg, an elimination half-life (t½β) of 4.53 ± 2.45 h, and a volume of distribution at steady-state (Vss) of 310.4 ± 106.4 mL/kg. Non-compartmental elimination half-life (t½λ) was 4.2 ± 1.1 h. After IM administration, drug pharmacokinetics was best described by a one-compartment open model. The peak plasma concentration (Cmax) was 15.1 ± 4.3 µg/mL; the time to reach Cmax (tmax), 1.66 ± 0.55 h; and the mean absorption time (MAT), 2.50 ± 1.42 h. Absorption was high, with a fraction of the dose absorbed (F) of 83.5 ± 22.4%. Menbutone was rapidly eliminated from plasma for both routes of administration, with a fast and high IM bioavailability.

Aim: To investigate the efficacy and tolerability of a cream (Rilastil Xerolact PB) containing a mixture of prebiotics and postbiotics, and to validate the PRURISCORE itch scale in the management of atopic dermatitis. Methods: The study is based on 396 subjects of both sexes in three age groups (i.e., infants, children, adults) suffering from mild/moderate Atopic Dermatitis, recruited from 8 European countries and followed for 3 months. Results: The product demonstrated good efficacy combined with good/very good tolerability in all age groups. In particular, SCORAD, PRURISCORE and IGA scores decreased significantly over the course of the study. The PRURISCORE was preferred to VAS by the vast majority of patients. Conclusion: Even though the role of prebiotics and postbiotics was not formally demonstrated since these substances were part of a complex formulation, it can be reasonably stated that prebiotics and postbiotics have safety and standardization features that probiotics do not have. In addition they are authorized by regulatory authorities, whereas topical probiotics are not.

Background: The Internet has become an important source for easy access to doping substances, where people and athletes may acquire, outside pharmacies and without a (medical) prescription. These online websites do not always offer quality-assured products, and are outside the regular distribution channels of medicines. The aim of this study was to estimate the availability and accessible information on the Internet about the sale of three doping substances (oxandrolone, DHEA, androstenedione).Methods: Cross-sectional exploratory study, being an observation at a point in time of the online availability of these three doping substances (WADA S1 category: anabolic agents), purchased from Spain, Puerto Rico, Canada, United States, Ukraine and Russia. The characteristics of the websites, the countries the webs sold to, the pharmaceutical forms offered and the recommendations for its use were analyzed by using a computer tool designed ad hoc.Results: There were significant differences between countries in the number of webpages that sold the products (Chi-square test, p < 0.05). Oxandrolone was available for purchase mainly when buying from Spain (27.12%) and Ukraine (26.58%), in websites dedicated to sports (77.26%). For DHEA, most of the pages offered it if the search was done from Canada (23.34%) and Russia (21.44%). Products containing androstenedione or DHEA are claimed to enhance sports performance or for sports use without providing details. Compared to the total number of websites checked, the proportion of pharmacies offering these products was low, ranging from 4.86% for DHEA to 15.79% for androstenedione.Conclusion: The three substances selected are easily available without control through the Internet. Only a small number of websites offering them were online pharmacies, and requested a prescription. Most of the doping substances are purchased from the country where they are requested. Product information described benefits for sports performance, but did not do the same with their side effects. It would be advisable for these products to be sold through pharmacies, to guarantee their quality and provide evidence-based information on their safe use, benefits and risks, and only with a prescription. Athletes should be encouraged to consult health professionals about those supplements suitable for their type of training and sports objectives.

The aim of this study was to examine whether motivation, support, basic-needs satisfaction, and social skills in physical education lessons differed among Chinese secondary students from rural areas depending on their sociodemographic profiles. Two hundred and seven students enrolled in a camp organized by a non-profit organization in Chengdu province (15.8 ± 0.8 years, 74% female and 26% male) completed validated Chinese versions of the pertinent questionnaires. Appropriate social skills were perceived higher by women that by men (z = 2.2; p = 0.014; r = 0.16). Inappropriate social skills (z = 2.9; p = 0.021; r = 0.22) were perceived higher among those students with lower annual home income (50,000 yuan or less). Perceived autonomy support (z = 2.9; p = 0.002; r = 0.20), basic-needs satisfaction (z = 2.9; p = 0.002; r = 0.20), and physical-education motivation (z = 4.2; p

Abstract Background There is a critical need for novel primary endpoints designed to detect early and subtle changes in cognition in clinical trials targeting the asymptomatic (preclinical) phase of Alzheimer’s disease (AD). The Alzheimer’s Prevention Initiative (API) Generation Program, conducted in cognitively unimpaired individuals at risk of developing AD (e.g., enriched by the apolipoprotein E (APOE) genotype), used a novel dual primary endpoints approach, whereby demonstration of treatment effect in one of the two endpoints is sufficient for trial success. The two primary endpoints were (1) time to event (TTE)—with an event defined as a diagnosis of mild cognitive impairment (MCI) due to AD and/or dementia due to AD—and (2) change from baseline to month 60 in the API Preclinical Composite Cognitive (APCC) test score. Methods Historical observational data from three sources were used to fit models to describe the TTE and the longitudinal APCC decline, both in people who do and do not progress to MCI or dementia due to AD. Clinical endpoints were simulated based on the TTE and APCC models to assess the performance of the dual endpoints versus each of the two single endpoints, with the selected treatment effect ranging from a hazard ratio (HR) of 0.60 (40% risk reduction) to 1 (no effect). Results A Weibull model was selected for TTE, and power and linear models were selected to describe the APCC score for progressors and non-progressors, respectively. Derived effect sizes in terms of reduction of the APCC change from baseline to year 5 were low (0.186 for HR = 0.67). The power for the APCC alone was consistently lower compared to the power of TTE alone (58% [APCC] vs 84% [TTE] for HR = 0.67). Also, the overall power was higher for the 80%/20% distribution (82%) of the family-wise type 1 error rate (alpha) between TTE and APCC compared to 20%/80% (74%). Conclusions Dual endpoints including TTE and a measure of cognitive decline perform better than the cognitive decline measure as a single primary endpoint in a cognitively unimpaired population at risk of AD (based on the APOE genotype). Clinical trials in this population, however, need to be large, include older age, and have a long follow-up period of at least 5 years to be able to detect treatment effects.

Abstract Background Animal models are increasingly used in Nursing science to study care approaches. Despite the scientific relevance and the ethical debate surrounding the use of experimental animals, there is a scarcity of scholarly literature exploring this topic in Nursing Schools. Aim To evaluate perceptions and attitudes of nursing students enrolled in a Pharmacology course on the use of experimental animals and implementation of alternative methods, by comparing the experience for two academic years. An interdisciplinary collaboration has also been developed. Methods A descriptive cross-sectional, quantitative study was developed. Undergraduate nursing students were enrolled in the Pharmacology subject at the University of Leon (Spain). The study was carried out in the Pharmacology facilities. Students followed a two-session practical class regarding experimental animals and alternative methods in the Pharmacology course (Degree in Nursing) in two different academic years (2019–20/2020–21). At the end of the activity, they answered a questionnaire to assess their opinions on the use of experimental animals and alternative methods in Pharmacology and the 3Rs principle. Results A comparison of the students’ perception with and without direct participation in the evaluation of promazine effects in mice was made. A total of 190 students participated in the teaching experience, providing high scores in all items (4–5 out of 5 points) regarding the teaching experience. Students became also aware of the advantages and disadvantages on the use of experimental animals, as well as the ethical considerations to bear in mind for their use and the need for alternative methods. Conclusions In the students’ opinion, the total replacement of animals by alternative techniques was very difficult, and they preferred to do the practice face-to-face. The alternative method designed was useful for the students to accept the employment of experimental animals in biomedical research and education, and know the legislation applied in the protection of animals.

Abstract Background Clinical trials have shown that erenumab is effective and well-tolerated for the preventive treatment of chronic migraine. To extend the results from clinical trials, we assessed the real-world efficacy and safety of erenumab in patients with chronic migraine from the outpatient clinic at the Danish Headache Center. Methods A 52-week, single-center, prospective, observation study of erenumab in adults with chronic migraine who are eligible for treatment with monoclonal antibodies against CGRP or its receptor in Denmark. The primary outcome was defined as proportion of patients who achieved ≥ 30% reduction in monthly migraine days (MMDs) from baseline to weeks 9–12. Results A total of 300 adult patients with chronic migraine were enrolled and received at least one dose of erenumab. At baseline, the mean (SD) number of monthly headache days was 23 ± 4.9 and mean number of MMDs was 16.8 ± 6.4. Of 300 enrolled patients, 273 (91.0%) patients completed 12 weeks of treatment, and 119 (39.7%) completed 52 weeks of treatment. The number of patients who achieved ≥ 30% reduction in MMDs from baseline to weeks 9–12 was 195 (71.4%) of 273 patients. Sustained ≥ 30% reduction in MMDs at all assessment periods throughout the 52-week treatment period was achieved by 102 (34%) of 300 patients. Adverse events occurred in 220 (73.3%) out of 300 patients. The most common adverse event was constipation. Treatment discontinuation due to lack of tolerability occurred in 41 (13.7%) patients. Conclusions Among adult patients with chronic migraine and previous failure of medications for migraine prevention, erenumab was found to be effective and well-tolerated.

Summary: Background: Anti-COVID-19 hyperimmune immunoglobulin (hIG) can provide standardized and controlled antibody content. Data from controlled clinical trials using hIG for the prevention or treatment of COVID-19 outpatients have not been reported. We assessed the safety and efficacy of subcutaneous anti-COVID-19 hyperimmune immunoglobulin 20% (C19-IG20%) compared to placebo in preventing development of symptomatic COVID-19 in asymptomatic individuals with SARS-CoV-2 infection. Methods: We did a multicentre, randomized, double-blind, placebo-controlled trial, in asymptomatic unvaccinated adults (≥18 years of age) with confirmed SARS-CoV-2 infection within 5 days between April 28 and December 27, 2021. Participants were randomly assigned (1:1:1) to receive a blinded subcutaneous infusion of 10 mL with 1 g or 2 g of C19-IG20%, or an equivalent volume of saline as placebo. The primary endpoint was the proportion of participants who remained asymptomatic through day 14 after infusion. Secondary endpoints included the proportion of individuals who required oxygen supplementation, any medically attended visit, hospitalisation, or ICU, and viral load reduction and viral clearance in nasopharyngeal swabs. Safety was assessed as the proportion of patients with adverse events. The trial was terminated early due to a lack of potential benefit in the target population in a planned interim analysis conducted in December 2021. ClinicalTrials.gov registry: NCT04847141. Findings: 461 individuals (mean age 39.6 years [SD 12.8]) were randomized and received the intervention within a mean of 3.1 (SD 1.27) days from a positive SARS-CoV-2 test. In the prespecified modified intention-to-treat analysis that included only participants who received a subcutaneous infusion, the primary outcome occurred in 59.9% (91/152) of participants receiving 1 g C19-IG20%, 64.7% (99/153) receiving 2 g, and 63.5% (99/156) receiving placebo (difference in proportions 1 g C19-IG20% vs. placebo, −3.6%; 95% CI -14.6% to 7.3%, p = 0.53; 2 g C19-IG20% vs placebo, 1.1%; −9.6% to 11.9%, p = 0.85). None of the secondary clinical efficacy endpoints or virological endpoints were significantly different between study groups. Adverse event rate was similar between groups, and no severe or life-threatening adverse events related to investigational product infusion were reported. Interpretation: Our findings suggested that administration of subcutaneous human hyperimmune immunoglobulin C19-IG20% to asymptomatic individuals with SARS-CoV-2 infection was safe but did not prevent development of symptomatic COVID-19. Funding: Grifols.

Menbutone is a drug currently approved in several European Union (EU) countries to treat digestive disorders in different animal species. The objective of this study was to establish the pharmacokinetic parameters resulting from intravenous (IV) and intramuscular (IM) administration of this drug in sheep. Menbutone was administered to 12 animals at the dose of 10 mg/kg for both IV and IM routes. Plasma samples were collected up to 24 h (15 points, IV route; 14 points, IM route). Concentrations were determined using high-performance liquid chromatography with photodiode-array (PDA) detection, following a method validated according to the EMEA/CHMP/EWP/192217/2009 guideline. Pharmacokinetic data were analyzed by non-compartmental methods. After IV administration, a total clearance (Cl) of 63.6 ± 13.6 mL/h/kg, a volume of distribution at steady-state (Vss) of 259.6 ± 52.7 mL/kg, and an elimination half-life (t½λ) of 6.08 ± 2.48 h were calculated. After IM administration, menbutone peak plasma concentration (Cmax) was 18.8 ± 1.9 μg/mL, the time to reach Cmax (tmax) 3.75 ± 0.45 h, the mean absorption time (MAT) 3.31 ± 1.36 h, and the fraction of dose absorbed (F) 103.1 ± 23.0 %. The results obtained indicate that menbutone absorption after IM administration is quick and complete.

A one-pot three-component synthesis of dihydropyrimidinones (DHPMs) via Biginelli reaction was carried out at 100 °C using benzaldehyde, ethyl acetoacetate and urea as reactants, in the presence of ethanol and free solvent, in heterogeneous catalytic medium. The Mo (30 wt%) metal oxides (Al2O3, SiO2 or MgO) used catalysts were prepared by sol-gel, impregnation and microemulsion methods and characterized by X-Ray Diffraction (XRD), Fourier Transform Infra Red (FTIR), Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), Energy Dispersive X-ray (EDX), Nitrogen Adsorption - Brunauer-Emmett-Teller (BET), and NH3-Temperature Programmed Desorption (TPD) methods. The Mo-SiO2 sample prepared by the sol-gel method exhibited the highest DHPM yield (87%), in free solvent with a reaction time of 30 min. The high efficiency, in the Biginelli reaction, of the Mo-SiO2 catalyst is due to its structural, textural and acid properties. Highly dispersed αMoO3 species of orthorhombic structure having a high contribution of strong acidic sites would be the active species in the Biginelli synthesis. Copyright © 2021 by Authors, Published by BCREC Group. This is an open access article under the CC BY-SA License (https://creativecommons.org/licenses/by-sa/4.0).

Abstract Background There is growing interest in identifying sensitive composite cognitive tests to serve as primary endpoints in preclinical Alzheimer’s disease (AD) treatment trials. We reported previously a composite cognitive test score sensitive to tracking preclinical AD decline up to 5 years prior to clinical diagnosis. Here we expand upon and refine this work, empirically deriving a composite cognitive test score sensitive to tracking preclinical AD decline up to 11 years prior to diagnosis and suitable for use as a primary endpoint in a preclinical AD trial. Methods This study used a longitudinal approach to maximize sensitivity to tracking progressive cognitive decline in people who progressed to the clinical stages of AD (n = 868) compared to those who remained cognitively unimpaired during the same time period (n = 989), thereby correcting for normal aging and practice effects. Specifically, we developed the Alzheimer’s Prevention Initiative Preclinical Composite Cognitive test (APCC) to measure very early longitudinal cognitive decline in older adults with preclinical AD. Data from three cohorts from Rush University were analyzed using a partial least squares (PLS) regression model to identify optimal composites within different time periods prior to diagnosis, up to 11 years prior to diagnosis. The mean-to-standard deviation ratio (MSDRs) is an indicator of sensitivity to change and was used to inform the final calculation of the composite score. Results The optimal composite, the APCC, is calculated: 0.26*Symbol Digit Modalities + 2.24*MMSE Orientation to Time + 2.14*MMSE Orientation to Place + 0.53*Logical Memory Delayed Recall + 1.36* Word List-Delayed Recall + 0.68*Judgment of Line Orientation + 1.39*Raven’s Progressive Matrices Matrices (subset of 9 items from A and B). The MSDR of the APCC in a population of preclinical AD individuals who eventually progress to cognitive impairment, compared to those who remained cognitively unimpaired during the same time period, was − 1.10 over 1 year. Conclusions The APCC is an empirically derived composite cognitive test score with high face validity that is sensitive to preclinical AD decline up to 11 years prior to diagnosis of the clinical stages of AD. The components of the APCC are supported by theoretical understanding of cognitive decline that occurs during preclinical AD. The APCC was used as a primary outcome in the API Generation Program trials.

Abstract Aims The objective of the present study is to assess the prognostic value of acute kidney injury (AKI) in the evolution of patients with heart failure (HF) using real‐world data. Methods and results Patients with a diagnosis of HF and with serial measurements of renal function collected throughout the study period were included. Estimated glomerular filtration rate (GFR) was calculated with the CKD‐EPI (Chronic Kidney Disease Epidemiology Collaboration). AKI was defined when a sudden drop in creatinine with posterior recovery was recorded. According to the Risk, Injury, Failure, Loss, and End‐Stage Renal Disease (RIFLE) scale, AKI severity was graded in three categories: risk [1.5‐fold increase in serum creatinine (sCr)], injury (2.0‐fold increase in sCr), and failure (3.0‐fold increase in sCr or sCr > 4.0 mg/dL). AKI incidence and risk of hospitalization and mortality after the first episode were calculated by adjusting for potential confounders. A total of 30 529 patients with HF were included. During an average follow‐up of 3.2 years, 5294 AKI episodes in 3970 patients (13.0%) and incidence of 3.3/100 HF patients/year were recorded. One episode was observed in 3161 (10.4%), two in 537 (1.8%), and three or more in 272 (0.9%). They were more frequent in women with diabetes and hypertension. The incidence increases across the GFR levels (Stages 1 to 4: risk 7.6%, 6.8%, 11.3%, and 12.5%; injury 2.1%, 2.0%, 3.3%, and 5.5%; and failure 0.9%, 0.6%. 1.4%, and 8.0%). A total of 3817 patients with acute HF admission were recorded during the follow‐up, with incidence of 38.4/100 HF patients/year, 3101 (81.2%) patients without AKI, 545 (14.3%) patients with one episode, and 171 (4.5%) patients with two or more. The number of AKI episodes [one hazard ratio (HR) 1.05 (0.98–1.13); two or more HR 2.01 (1.79–2.25)] and severity [risk HR 1.05 (0.97–1.04); injury HR 1.41 (1.24–1.60); and failure HR 1.90 (1.64–2.20)] increases the risk of hospitalization. A total of 10 560 deaths were recorded, with incidence of 9.3/100 HF patients/year, 8951 (33.7%) of subjects without AKI episodes, 1180 (11.17%) of subjects with one episode, and 429 (4.06%) with two or more episodes. The number of episodes [one HR 1.05 (0.98–1.13); two or more HR 2.01 (1.79–2.25)] and severity [risk 1.05 confidence interval (CI) (0.97–1.14), injury 1.41 (CI 1.24–1.60), and failure 1.90 (CI 1.64–2.20)] increases mortality risk. Conclusions The study demonstrated the worse prognostic value of sudden renal function decline in HF patients and pointed to those with more future risk who require review of treatment and closer follow‐up.

IntroductionThe activation of perivascular fibers and the consequent release of vasoactive peptides, including the vasoactive intestinal polypeptide (VIP), play a role in migraine pathogenesis. A 2-h infusion of VIP provoked migraine, but the mechanisms remain unknown. We investigated whether 2-h infusion of VIP caused alterations in plasma levels of the calcitonin gene-related peptide (CGRP) and whether any changes might be related to the induced migraine attacks.Materials and MethodsWe enrolled individuals with episodic migraine without aura and healthy participants to randomly receive a 2-h infusion of either VIP (8 pmol/kg/min) or placebo (sterile saline) in two randomized, placebo-controlled crossover trials. We collected clinical data and measured plasma levels of VIP and CGRP at fixed time points: at baseline (T0) and every 30 min until 180 min (T180) after the start of the infusion.ResultsBlood samples were collected from patients with migraine (n = 19) and healthy individuals (n = 12). During VIP infusion, mixed effects analysis revealed a significant increase in plasma CGRP (p = 0.027) at T30 (vs. T180, adjusted p-value = 0.039) and T60 (vs. T180, adjusted p-value = 0.027) in patients with migraine. We found no increase in plasma CGRP during VIP-induced migraine attacks (p = 0.219). In healthy individuals, there was no increase in plasma CGRP during VIP (p = 0.205) or placebo (p = 0.428) days.DiscussionPlasma CGRP was elevated in patients with migraine during a prolonged infusion of VIP, but these alterations were not associated with VIP-induced migraine attacks. Given the exploratory design of our study, further investigations are needed to clarify the role of CGRP in VIP-induced migraine.Clinical Trial RegistrationClinicalTrials.gov, identifier: NCT03989817 and NCT04260035.

Carreira esportiva compreende um conjunto de atividades esportivas que se sucedem em estágios e transições desde a iniciação até o momento que atletas decidem encerrar a sua participação no esporte de maneira voluntária ou não, buscando atingir altos níveis de performance em um ou vários eventos esportivos (Stambulova e Wylleman, 2014). É um processo caracterizado por diferentes interferências (família, colegas, treinadores, contexto, atividade) e constantes mudanças, algumas possíveis de serem planejadas e organizadas previamente sem apresentar grandes riscos ou dificuldades para a carreira de atletas (transições normativas), ou que ocorrem de maneira inesperada e provocam problemas para lidar com essas situações – como lesões e mudanças de clube (transições não normativas) (Folle et al., 2016).

Histone methylation-modifiers, such as EZH2 and KMT2D, are recurrently altered in B-cell lymphomas. To comprehensively describe the landscape of alterations affecting genes encoding histone methylation-modifiers in lymphomagenesis we investigated whole genome and transcriptome data of 186 mature B-cell lymphomas sequenced in the ICGC MMML-Seq project. Besides confirming common alterations of KMT2D (47% of cases), EZH2 (17%), SETD1B (5%), PRDM9 (4%), KMT2C (4%), and SETD2 (4%), also identified by prior exome or RNA-sequencing studies, we here found recurrent alterations to KDM4C in chromosome 9p24, encoding a histone demethylase. Focal structural variation was the main mechanism of KDM4C alterations, and was independent from 9p24 amplification. We also identified KDM4C alterations in lymphoma cell lines including a focal homozygous deletion in a classical Hodgkin lymphoma cell line. By integrating RNA-sequencing and genome sequencing data we predict that KDM4C structural variants result in loss-offunction. By functional reconstitution studies in cell lines, we provide evidence that KDM4C can act as a tumor suppressor. Thus, we show that identification of structural variants in whole genome sequencing data adds to the comprehensive description of the mutational landscape of lymphomas and, moreover, establish KDM4C as a putative tumor suppressive gene recurrently altered in subsets of B-cell derived lymphomas.

ABSTRACT The sports career is a process through which the athletes voluntarily seek to achieve high levels of sport performance, however, how the development of international elite squash athletes has occurred in different periods of their sports career is not known. This study aimed at describing and assessing the sport trajectory of Brazilian international elite squash athletes at different periods of their career, in light of dynamic elements, that is, personal engagement, quality relationships and appropriate settings. Semi-structured interviews were carried out based on the Personal Assets Framework (PAF). The interviews were applied to six athletes (three males and three females) and evaluated according to the Thematic Analysis (TA) method. The results showed that personality traits, interpersonal relationships and the sport practice settings enabled the squash players to develop their sports career. In conclusion, these three aspects when acting concurrently can favor the development of international elite squash athletes.

Cutaneous neoplasms from different cell types can exist within the same lesion. These can be classified into four subtypes which are collision tumour, combined tumour, colonization and biphenotypic tumour. The presence of a melanoma component in these tumours is very rare. Herein we present a singular case of two synchronous dineoplastic cutaneous tumours: a squamomelanocytic tumour and a collision consisting of melanoma and seborrheic keratosis. Additionally, we performed a literature review of all squamomelanocytic tumours published until date, including our case.

Introduction: Religiosity and sexuality present numerous interconnections. Little is known regarding the specific causal pathways between each religiosity dimension and sexual behavior. The objectives of this study were (1) to explore the relationship between religiosity (measured through attendance at religious services, salience, and prayer) and sexual initiation in adolescents and (2) to establish the role of sexual permissiveness as mediator of the impact produced by religiosity in sexual initiation.Methods: This study analyzes data from an ongoing school-based international study examining what young people feel and think about relationships, love, and sexuality. An anonymous, self-administered online questionnaire was developed in Spanish. A total of 4,366 students, aged 14–18, completed the questionnaire. A final sample of 2,919 questionnaires was analyzed. Two unconditional logistic regression models were fit with religiosity variables and possible confounders as independent variables (with and without permissiveness, respectively). The dependent variable was sexual initiation. A final path analysis was performed to further understand the results.Results: Our study highlights that, in predominantly Catholic and Spanish-speaking countries, the fact of attending church and praying may greatly contribute to postponing sexual relations during adolescence, even independently of their attitudes on sexual permissiveness. Conversely, the effect of salience on sexual initiation seems to be fostered only through the mediation of sexual permissiveness. Our findings point to an indirect effect of the three religiosity dimensions (and in particular, religious salience) through permissive attitudes.Conclusion: Religiosity could be a relevant factor to explain sexual initiation during adolescence.

Background: Media outlets influence social attitudes toward health habits. The analysis of tweets has become a tool for health researchers.Objective: The objective of this study was to investigate the distribution of tweets about women's health and the interest generated among Twitter users.Methods: We investigated tweets posted by 25 major U.S. media outlets about pre-menopausal and post-menopausal women's health between January 2009 and December 2019 as well as the retweets generated. In addition, we measured the sentiment analysis of these tweets as well as their potential dissemination.Results: A total of 376 tweets were analyzed. Pre-menopausal women's health accounted for most of the tweets (75.3%). Contraception was the main focus of the tweets, while a very limited number were related to infertility (1.4%). With regard to medical content, the effectiveness of contraceptive methods was the most frequent topic (46.2%). However, tweets related to side effects achieved the highest retweet-to-tweet ratio (70.3). The analysis of sentiments showed negative perceptions on tubal ligation.Conclusions: The U.S. media outlets analyzed are more interested in pre-menopausal than in post-menopausal women health and focused their content on contraception, while Twitter users showed greater interest in side effects.

Pressures are mounting for the adoption of a Global Biodiversity Framework that transforms conservation and sustainable use efforts worldwide. Underlying this challenge is the biodiversity paradox: biological diversity predominantly concentrates in the tropics, while human, institutional, and financial resources are primarily located at higher latitudes both north and south. Addressing the biodiversity paradox requires the expansion and mobilization of human, institutional and financial resources around the world. We outline a model championed by the IUCN Species Survival Commission (SSC) that builds on the Species Conservation Cycle (Assess-Plan-Act-Network-Communicate) and recognizes that most conservation action occurs at the national or local level. Various strategies are applied to this end by the partners of Reverse the Red, a global movement that ignites strategic cooperation and science-based action to ensure the survival of wild species and ecosystems. The SSC contributes to Reverse the Red through two primary strategies: National Species Specialist Groups and Centers for Species Survival. By building on existing expert networks and catalyzing efforts with established local institutions, we aim to significantly expand capacity to implement conservation action at the national level and reverse the negative trends indicated by the IUCN Red List of Threatened Species and the Red List of Ecosystems.

Purpose: To compare the surgical duration for routine phacoemulsification surgeries in residents with and without virtual simulator training. Methods: Retrospective cohort study of operative times of routine phacoemulsification cataract surgeries performed by 29 different third-year residents rotating at one academic institution. One group underwent mandatory virtual cataract surgery simulator training (SIM) in their second year of residency before starting surgeries while the other group did not undergo any simulator training (NOSIM). Outcomes measured were comparative surgical times and vitreous loss rates between groups in their third year of residency. Results: 722 surgeries were included. Surgeries in the SIM group were on average 6.7 min (min) shorter compared to the NOSIM group (P = 0.0001). Although both groups required less time for surgery over the course of the academic year, regression analysis showed that NOSIM group residents overall required 17% longer time for an uncomplicated clear corneal phacoemulsification surgery (incidence rate ratio 1.17; p = 0.0001). In the final month of their residency residents in the SIM group (32.2 ± 3 min) were 9 min faster than NOSIM peers (41.2 ± 3 min mean ± SE; p = 0.02). Vitreous loss rates were 1.4% in the SIM group and 3.6% in the NOSIM group (p = 0.06). Conclusion and Importance: Early and continuous implementation of mandatory virtual simulator surgical training before starting intraocular surgeries significantly decreases operative times in third year residents learning phacoemulsification compared to non-simulator trained peers.

Roquin targets are known to contain two types of sequence-structure motifs, the constitutive and the alternative decay elements (CDE and ADE). Here, the authors describe a linear Roquin binding element (LBE) also involved in target recognition, and show that Roquin binding affects the translation of a subset of targeted mRNAs.

Abstract The beta‐site amyloid precursor protein cleaving enzyme‐1 (BACE‐1) initiates the generation of amyloid‐β (Aβ), and the amyloid cascade leading to amyloid plaque deposition, neurodegeneration, and dementia in Alzheimer's disease (AD). Clinical failures of anti‐Aβ therapies in dementia stages suggest that treatment has to start in the early, asymptomatic disease states. The BACE‐1 inhibitor CNP520 has a selectivity, pharmacodynamics, and distribution profile suitable for AD prevention studies. CNP520 reduced brain and cerebrospinal fluid (CSF) Aβ in rats and dogs, and Aβ plaque deposition in APP‐transgenic mice. Animal toxicology studies of CNP520 demonstrated sufficient safety margins, with no signs of hair depigmentation, retina degeneration, liver toxicity, or cardiovascular effects. In healthy adults ≥ 60 years old, treatment with CNP520 was safe and well tolerated and resulted in robust and dose‐dependent Aβ reduction in the cerebrospinal fluid. Thus, long‐term, pivotal studies with CNP520 have been initiated in the Generation Program.

The pharmacokinetic interaction between a benzimidazole (albendazole, ABZ) and a choleretic drug (menbutone, MEN) was evaluated in sheep. The plasma disposition of albendazole sulfoxide (ABZSO, active metabolite) and albendazole sulfone (ABZSO2, inactive metabolite) was investigated following an oral administration of albendazole (ABZ) (5 mg/kg) alone or with menbutone (MEN) (intramuscular, 10 mg/kg). Blood samples were collected over 3 days post-treatment, and drug plasma concentrations were measured by high performance liquid chromatography (HPLC). ABZSO was measured from 0.5 to 48 h, and ABZSO2 from 2 to 60 h. No parent drug was detected at any sampling time. Mean maximum plasma concentration (Cmax) and the area under the plasma concentration-time curve (AUC) were 12.8% and 21.5% higher for ABZSO when ABZ and MEN were administered together, which indicates a significant increase in the amount absorbed. The rate of absorption was not modified, with similar values for the time to reach Cmax (tmax) (11.5 h with ABZ + MEN and 10.7 h with ABZ treatment), although no significant differences were observed for these latter pharmacokinetic parameters. Regarding ABZSO2, Cmax, AUC and tmax values were similar after both treatments (ABZ or ABZ + MEN). The results obtained indicate that co-administration of ABZ and MEN may be an interesting and practical option to increase the efficacy of this anthelmintic.

Artificial Intelligence is creating a paradigm shift in health care, with phenotyping patients through clustering techniques being one of the areas of interest. Objective: To develop a predictive model to classify heart failure (HF) patients according to their left ventricular ejection fraction (LVEF), by using available data from Electronic Health Records (EHR). Subjects and methods: 2854 subjects over 25 years old with a diagnosis of HF and LVEF, measured by echocardiography, were selected to develop an algorithm to predict patients with reduced EF using supervised analysis. The performance of the developed algorithm was tested in heart failure patients from Primary Care. To select the most influentual variables, the LASSO algorithm setting was used, and to tackle the issue of one class exceeding the other one by a large amount, we used the Synthetic Minority Oversampling Technique (SMOTE). Finally, Random Forest (RF) and XGBoost models were constructed. Results: The full XGBoost model obtained the maximum accuracy, a high negative predictive value, and the highest positive predictive value. Gender, age, unstable angina, atrial fibrillation and acute myocardial infarct are the variables that most influence EF value. Applied in the EHR dataset, with a total of 25,594 patients with an ICD-code of HF and no regular follow-up in cardiology clinics, 6170 (21.1%) were identified as pertaining to the reduced EF group. Conclusion: The obtained algorithm was able to identify a number of HF patients with reduced ejection fraction, who could benefit from a protocol with a strong possibility of success. Furthermore, the methodology can be used for studies using data extracted from the Electronic Health Records.

Abstract Background Considering the high percentage of couples in which one or both members are HIV negative, the frequency of transmission among non-regular partners and the probabilities of non-disclosure, attention should be paid to people getting a negative HIV test at the Voluntary Counseling and Testing (VCT). Research has shown that a negative HIV test may be followed by a change in sexual behaviours. In Sub-Saharan Africa, where most HIV infections occur, there are few studies that have analysed the factors associated with changes in sexual risk behaviours after a negative HIV test at the VCT clinic. The aim of this project is to evaluate the specific factors associated with changes in sexual behaviours, three months after a negative result in an HIV test, and to analyse the effect of counseling and testing on HIV-related knowledge of participants in an outpatient centre of Kinshasa (Democratic Republic of Congo). Methods and design Prospective cohort study from December 2014 until March 2016. People 15–60 year old that received VCT at Monkole Hospital (Kinshasa) were followed three months after they got a negative HIV test. In a face-to-face interview, participants replied to a baseline and a follow-up research questionnaire on HIV-related knowledge, attitudes and behaviours. At follow-up respondents were also offered a new HIV test and additional HIV counseling. Four hundred and fifteen participants completed the baseline questionnaire and 363 (87 %) came back for their 3-month follow up. Discussion This is the first longitudinal study in the DRC that evaluates the factors associated with changes in sexual behaviours after a negative HIV test at the VCT. Participants attending the VCT services within a clinical setting are a good study population as they can be good transmitters of preventive information for other people with no access to health facilities.

Preeclampsia is a disorder specific of the human being that appears after 20 weeks of pregnancy, characterized by new onset of hypertension and proteinuria. Abnormal placentation and reduced placental perfusion associated to impaired trophoblast invasion and alteration in the compliance of uterine spiral arteries are the early pathological findings that are present before the clinical manifestations of preeclampsia. Later on, the endothelial and vascular dysfunction responsible of the characteristic vasoconstriction of preeclampsia appear. Different nutritional risk factors such as a maternal deficit in the intake of calcium, protein, vitamins and essential fatty acids, have been shown to play a role in the genesis of preeclampsia, but also an excess of weight gain during pregnancy or a pre-pregnancy state of obesity and overweight, which are associated to hyperinsulinism, insulin resistance and maternal systemic inflammation, are proposed as one of the mechanism that conduce to endothelial dysfunction, hypertension, proteinuria, thrombotic responses, multi-organ damage, and high maternal mortality and morbidity. Moreover, it has been demonstrated that pregnant women that suffer preeclampsia will have an increased risk of future cardiovascular disease and related mortality in their later life. In this article we will discuss the results of studies performed in different populations that have shown an interrelationship between obesity and overweight with the presence of preeclampsia. Moreover, we will review some of the common mechanisms that explain this interrelationship, particularly the alterations in the L-arginine/nitric oxide pathway as a crucial mechanism that is common to obesity, preeclampsia and cardiovascular diseases.

Background: Functional deletion of the Scn9a (sodium voltage-gated channel alpha subunit 9) gene encoding sodium channel Nav1.7 makes humans and mice pain-free. Opioid signalling contributes to this analgesic state. We have used pharmacological and genetic approaches to identify the opioid receptors involved in this form of analgesia. We also examined the regulation of proenkephalin expression by the transcription factor Nfat5 that binds upstream of the Penk gene. Methods: We used specific µ-, δ- and κ-opioid receptor antagonists alone or in combination to examine which opioid receptors were necessary for Nav1.7 loss-associated analgesia in mouse behavioural assays of thermal pain. We also used µ- and δ-opioid receptor null mutant mice alone and in combination in behavioural assays to examine the role of these receptors in Nav1.7 knockouts pain free phenotype. Finally, we examined the levels of Penk mRNA in Nfat5-null mutant mice, as this transcription factor binds to consensus sequences upstream of the Penk gene. Results: The pharmacological block or deletion of both µ- and δ-opioid receptors was required to abolish Nav1.7-null opioid-related analgesia. κ-opioid receptor antagonists were without effect. Enkephalins encoded by the Penk gene are upregulated in Nav1.7 nulls. Deleting Nfat5, a transcription factor with binding motifs upstream of Penk, induces the same level of enkephalin mRNA expression as found in Nav1.7 nulls, but without consequent analgesia. These data confirm that a combination of events linked to Scn9a gene loss is required for analgesia. Higher levels of endogenous enkephalins, potentiated opioid receptors, diminished electrical excitability and loss of neurotransmitter release together contribute to the analgesic phenotype found in Nav1.7-null mouse and human mutants. Conclusions: These observations help explain the failure of Nav1.7 channel blockers alone to produce analgesia and suggest new routes for analgesic drug development.

This cross-sectional study assesses the association between age of sexual initiation during adolescence and a selection of well-being outcomes regarding that first relationship. High-school adolescents from El Salvador (2,686) and from Peru (3,399) replied to a paper-pencil questionnaire. Those who were sexually initiated replied to several questions regarding their age at sexual initiation, condom use, satisfaction and reasons/circumstances for that sexual relationship. Approximately 19% of participants were sexually initiated (n = 1,179). After retaining participants with valid responses and with sexual initiation ages between 13 and 17, the final sample for this paper consisted of 996 sexually initiated participants (526 Salvadorians and 470 Peruvians). Multiple logistic regression analyses showed that those who initiated sex at earlier ages had worse outcomes compared to those who initiated at older ages. Specifically, they had lower odds of having used a condom, of having good memories of that experience and of having had that first relationship because they were in love. Conversely, they had higher odds of having had that first sexual relationship as a result of peer pressure (“Most of my friends already had sex”), because of partner pressure (“I was afraid to lose him/her,” “My partner told me he/she would leave me” or “I did not know how to say no to a person who insisted”), or as a consequence of different forms of impaired autonomy (“I was under the influence of alcohol or drugs” or “As a consequence of seeing sexual images”). Results show that sex at earlier ages is associated with worse adolescent health and well-being outcomes.

INTRODUCTION:Sexual violence, an HIV determinant, is an integrated behavior in the D.R.Congo. We aimed to analyze the prevalence of forced sexual intercourse (FSI) among people receiving HIV Voluntary Counseling and Testing in a hospital in Kinshasa, and its association with socio-demographics, behaviors and HIV status. METHODOLOGY:Case-control study (2010-2012). Two-hundred and seventy-four cases with a new HIV+ test and 1,340 controls with an HIV- test were interviewed about HIV-related knowledge, attitudes and behaviors, including FSI. RESULTS:Thirty-four percent of the participants declared having had FSI (38% of women and 32% of men). Being a woman, aged 25-49 and reporting multiple sexual partners were associated with reporting FSI. For men, being single was protective against FSI; and cohabiting, having a high socioeconomic status, and alcohol consumption increased the odds. For women, being single, divorced/separated and widow was associated with reporting FSI. A significant positive association was found between FSI and an HIV positive test. CONCLUSION:Among our Congolese population, FSI was strongly associated with HIV infection and it was also associated with alcohol consumption and multiple sexual partnerships, other key HIV determinants. These behaviors need to be identified as potential risk factors of FSI during counseling interventions. Researchers, practitioners and decision-makers should work together to get violence prevention integrated into health, social and educational policies.

Glucocorticoids (GC) induce cardiometabolic risk while atherosclerosis is a chronic inflammation involving immunity. GC are immune suppressors, and the adrenocorticotrophic hormone (ACTH) has immune modulator activities. Both may act in atherothrombotic inflammation involving immune cells (IMNC). Aim. To investigate adhesion and activation surface cell markers (CDs) of peripheral IMNC in endogenous Cushing syndrome (CS) and the immune modulator role of ACTH. Material and Methods. 16 ACTH-dependent CS (ACTH-D), 10 ACTH-independent (ACTH-ID) CS, and 16 healthy controls (C) were included. Leukocytes (Leuc), monocytes (MN), lymphocytes (Lym), and neutrophils (N) were analyzed by flow cytometry for atherosclerosis previously associated with CDs. Results. Leuc, N, and MN correlated with CS (p

Es importante para la historia del arte mexicano considerar la posibilidad de una continuidad del arte fantástico, desde José Guadalupe Posada hasta la pintura figurativa de fin del siglo XX y comienzos de XXI. Mi propuesta se basa en el libro de la historiadora Ida Rodríguez Prampolini, El surrealismo y el arte fantástico de México, escrito en 1969. Para una definición más amplia e incluyente recurro a la tesis literaria del escritor mexicano Omar Nieto Arroyo, publicada en 2015. Desde esta lejanía podremos ver claramente el hilo conductor de la producción fantástica mexicana, y por ende lo más importante: la estupenda maleabilidad del género para mostrar todo tipo de conceptos. Como un ejemplo del arte fantástico de México en la actualidad presento la obra del pintor Daniel Lezama.

INTRODUÇÃO: A doença cardiovascular é a principal causa de mortalidade de pacientes em hemodiálise. Quando consideradas todas as causas de morte, aproximadamente 30% são classificadas como parada cardíaca, morte de causa desconhecida ou arritmia cardíaca. O prolongamento do tempo de despolarização e repolarização ventriculares, medido pela aferição do intervalo QT no eletrocardiograma de repouso, tem emergido como preditor de arritmias ventriculares complexas, uma importante causa de morte súbita cardíaca. OBJETIVOS: Determinar as alterações eletrocardiográficas presentes em pacientes sob hemodiálise (HD), aferir o intervalo QT e sua relação com variáveis clínicas e laboratoriais. MÉTODOS: Pacientes com idade acima de 18 anos em programa de hemodiálise foram abordados para participarem do estudo, e após anuência, foram submetidos ao exame de eletrocardiograma de 12 derivações. Dados clínicos foram revisados para avaliar a presença de comorbidades, além da aferição de medidas antropométricas e da pressão arterial. Amostras de sangue foram coletadas para determinação da hemoglobina e níveis séricos de cálcio, fósforo e de potássio. RESULTADOS: Cento e setenta e nove pacientes foram incluídos no estudo. A maioria era do sexo masculino (64,8%) e da raça branca (54,7%); a idade média foi de 58,5 ± 14,7 anos. Aproximadamente 50% dos pacientes apresentaram ao menos um distúrbio de condução elétrica. Cerca de 50% apresentaram prolongamento do intervalo QTc e experimentaram aumento significativo na frequência de hipertrofia ventricular esquerda (HVE), alterações do ritmo cardíaco, bloqueios de ramo e mais baixos índices de massa corporal (IMC), quando comparados aos pacientes com intervalo QTc normal. CONCLUSÕES: Pacientes com doença renal crônica (DRC) em hemodiálise apresentam elevada frequência de achados eletrocardiográficos anormais, incluindo alta prevalência de pacientes com intervalo QTc prolongado. O presente estudo encontrou, ainda, associação significativa entre o intervalo QTc prolongado com a presença de Diabetes e de valores mais baixos para o IMC.

Two major lineages of beetles inhabit cycad cones in the New World: weevils (Curculionoidea) in the subtribe Allocorynina, including the genera Notorhopalotria Tang and O’Brien, Parallocorynus Voss, Protocorynus O’Brien and Tang and Rhopalotria Chevrolat, and beetles in the family Erotylidae, including the genus Pharaxonotha Reitter. Analysis of the 16S ribosomal RNA (rRNA) mitochondrial gene as well as cladistic analysis of morphological characters of the weevils indicate four major radiations, with a probable origin on the cycad genus Dioon Lindl. and comparatively recent host shifts onto Zamia L. Analysis of the 16S rRNA gene for erotylid beetles indicates that an undescribed genus restricted to New World Ceratozamia Brongn. is the most early-diverging clade, and this lineage is sister to a large radiation of the genus Pharaxonotha onto Zamia, with apparent host shifts onto Dioon and Ceratozamia. Analysis of beetles are in accord with current models of continental drift in the Caribbean basin, support some proposed species groupings of cycads, but not others, and suggest that pollinator type may impact population genetic structure in their host cycads.