Rare Choristoma of the Tarsal Conjunctiva: Critical Inspection Prevents Unnecessary Mutilation

We report a case of a 26-year-old male patient with an incidental finding of a flesh-colored tumor with few vellus hairs on its surface, located on the fornix and the tarsal conjunctiva of the left lower eyelid. Histology of the biopsy showed a choristoma consisting of abundant vellus hairs, sebaceous glands, and sparse lacrimal gland tissue. Recognition of conjunctival vellus hairs is significant and raises the suspected diagnosis of choristoma, which can be confirmed by a small sample biopsy. A complete excision is unnecessary and possible surgical complications can be prevented. Choristomas of the tarsal conjunctiva are very rare and, to our knowledge, this is the first histological documentation of a choristoma containing vellus hair located on the tarsal conjunctiva. In addition, we review the histopathological findings of choristomas and their differential diagnoses. Keywords: Case report; Choristoma; Hamartoma; Tarsal choristoma; Vellus hai

What are the social outcomes of climate policies? A systematic map and review of the ex-post literature

It is critical to ensure climate and energy policies are just, equitable and beneficial for communities, both to sustain public support for decarbonisation and address multifaceted societal challenges. Our objective in this article is to examine the diverse social outcomes that have resulted from climate policies, in varying contexts worldwide, over the past few decades. We review 203 ex-post climate policy assessments that analyse social outcomes in the literature. We systematically and comprehensively map out this work, identifying articles on carbon, energy and transport taxes, feed-in-tariffs, subsidies, direct procurement policies, large renewable deployment projects, and other regulatory and market-based interventions. We code each article in terms of their studied social outcomes and effects, with a focus on electricity access, energy affordability, community cohesion, employment, distributional and equity issues, livelihoods and poverty, procedural justice, subjective well-being and drudgery. Our analysis finds that climate and energy policies often fall short of delivering positive social outcomes. Nonetheless, across country contexts and policy types there are manifold examples of climate policymaking that does deliver on both social and climate goals. This requires attending to distributive and procedural justice in policy design, and making use of appropriate mechanisms to ensure that policy costs and benefits are fairly shared. We emphasize the need to further advance ex-post policy assessments and learn about what policies work for a just transition

Accuracy of genotype imputation and genomic predictions in a two-generation farmed Atlantic salmon population using highdensity and low-density SNP panels

Made available in DSpace on 2018-12-11T16:52:25Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-04-01The objectives of this study were: (i) to assess genotype imputation accuracy in different scenarios using genome-wide single nucleotide polymorphisms (SNP) data from a population comprising two generations of farmed Atlantic salmon and (ii) to assess the accuracy of genomic predictions for a quantitative trait (body weight) using the imputed genotypes. The pedigree consisted of 53 parents and 1069 offspring genotyped using a high-density SNP panel (50 K). Two groups were created: Group A: 90% of the offspring were included into training and 10% into validation sets; Group B: 10% of the offspring were included into training and 90% into validation sets. Different scenarios of available genotypic information from relatives were tested for the two groups previously described. Imputation was performed using three in silico low-density panels (0.5, 3 and 6 K) with all markers except the markers present on the low-density panel masked in the validation sets. The accuracy of genomic selection was tested using the scenarios that resulted in the best and the worst imputation accuracy for the three low density panels and were compared to accuracy obtained from pedigree-based best linear unbiased prediction (PBLUP) and genomic predictions using the 50 K SNP panel. In general, imputation accuracy ranged from 0.74 to 0.98 depending on scenario. For the best scenario with the highest number of animals in reference population (Group A), the accuracy of imputation ranged from 0.95 to 0.98 depending on the low-density panel used. For the best scenario with the lowest number of animals in reference population (Group B), the accuracy of imputation ranged from 0.94 to 0.98 depending on the low-density panel used. In general, the number of SNPs in the low-density panels had a greater influence on the accuracy of imputation than the size of the reference set. The accuracies of genomic predictions using imputed genotypes, ranging from 0.71 to 0.73, outperformed PBLUP (0.66) and were identical or very similar to the use of all true genotype data (0.73). The high imputation and genomic prediction accuracy suggest that the imputation of genotypes from low density (0.5 to 3 K) to high density (50 K) could be a cost-effective strategy for the feasibility of the practical implementation of genomic selection in Atlantic salmon.Facultad de Ciencias Veterinarias y Pecuarias Universidad de Chile, Av. Santa Rosa 11735School of Agricultural and Veterinarian Sciences São Paulo State University (UNESP), Jaboticabal, Via de Acesso Prof. Paulo Donato CastellaneAquainnovo, Cardonal S/NThe Roslin Institute and Royal (Dick) School of Veterinary Studies University of EdinburghNúcleo Milenio INVASALSchool of Agricultural and Veterinarian Sciences São Paulo State University (UNESP), Jaboticabal, Via de Acesso Prof. Paulo Donato Castellan

Histone deacetylase adaptation in single ventricle heart disease and a young animal model of right ventricular hypertrophy.

BackgroundHistone deacetylase (HDAC) inhibitors are promising therapeutics for various forms of cardiac diseases. The purpose of this study was to assess cardiac HDAC catalytic activity and expression in children with single ventricle (SV) heart disease of right ventricular morphology, as well as in a rodent model of right ventricular hypertrophy (RVH).MethodsHomogenates of right ventricle (RV) explants from non-failing controls and children born with a SV were assayed for HDAC catalytic activity and HDAC isoform expression. Postnatal 1-day-old rat pups were placed in hypoxic conditions, and echocardiographic analysis, gene expression, HDAC catalytic activity, and isoform expression studies of the RV were performed.ResultsClass I, IIa, and IIb HDAC catalytic activity and protein expression were elevated in the hearts of children born with a SV. Hypoxic neonatal rats demonstrated RVH, abnormal gene expression, elevated class I and class IIb HDAC catalytic activity, and protein expression in the RV compared with those in the control.ConclusionsThese data suggest that myocardial HDAC adaptations occur in the SV heart and could represent a novel therapeutic target. Although further characterization of the hypoxic neonatal rat is needed, this animal model may be suitable for preclinical investigations of pediatric RV disease and could serve as a useful model for future mechanistic studies

Narrow band imaging for the detection of gastric intestinal metaplasia and dysplasia during surveillance endoscopy

Background: Surveillance of premalignant gastric lesions relies mainly on random biopsy sampling. Narrow band imaging (NBI) may enhance the accuracy of endoscopic surveillance of intestinal metaplasia (IM) and dysplasia. We aimed to compare the yield of NBI to white light endoscopy (WLE) in the surveillance of patients with IM and dysplasia. Methods: Patients with previously identified gastric IM or dysplasia underwent a surveillance endoscopy. Both WLE and NBI were performed in all patients during a single procedure. The sensitivity of WLE and NBI for the detection of premalignant lesions was calculated by correlating endoscopic findings to histological diagnosis. Results: Forty-three patients (28 males and 15 females, mean age 59 years) were included. IM was diagnosed in 27 patients; 20 were detected by NBI and WLE, four solely by NBI and three by random biopsies only. Dysplasia was detected in seven patients by WLE and NBI and in two patients by random biopsies only. Sixty-eight endoscopically detected lesions contained IM: 47 were detected by WLE and NBI, 21 by NBI only. Nine endoscopically detected lesions demonstrated dysplasia: eight were detected by WLE and NBI, one was detected by NBI only. The sensitivity, specificity, positive and negative predictive values for detection of premalignant lesions were 71, 58, 65 and 65% for NBI and 51, 67, 62 and 55% for WLE, respectively. Conclusions: NBI increases the diagnostic yield for detection of advanced premalignant gastric lesions compared to routine WLE

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

COVID-19 severity and mortality in patients with CLL: an update of the international ERIC and Campus CLL study

Patients with chronic lymphocytic leukemia (CLL) may be more susceptible to Coronavirus disease 2019 (COVID-19) due to age, disease, and treatment-related immunosuppression. We aimed to assess risk factors of outcome and elucidate the impact of CLL-directed treatments on the course of COVID-19. We conducted a retrospective, international study, collectively including 941 patients with CLL and confirmed COVID-19. Data from the beginning of the pandemic until March 16, 2021, were collected from 91 centers. The risk factors of case fatality rate (CFR), disease severity, and overall survival (OS) were investigated. OS analysis was restricted to patients with severe COVID-19 (definition: hospitalization with need of oxygen or admission into an intensive care unit). CFR in patients with severe COVID-19 was 38.4%. OS was inferior for patients in all treatment categories compared to untreated (p < 0.001). Untreated patients had a lower risk of death (HR = 0.54, 95% CI:0.41–0.72). The risk of death was higher for older patients and those suffering from cardiac failure (HR = 1.03, 95% CI:1.02–1.04; HR = 1.79, 95% CI:1.04–3.07, respectively). Age, CLL-directed treatment, and cardiac failure were significant risk factors of OS. Untreated patients had a better chance of survival than those on treatment or recently treated

The evolving landscape of COVID‐19 and post‐COVID condition in patients with chronic lymphocytic leukemia: A study by ERIC, the European research initiative on CLL

In this retrospective international multicenter study, we describe the clinical characteristics and outcomes of patients with chronic lymphocytic leukemia (CLL) and related disorders (small lymphocytic lymphoma and high-count monoclonal B lymphocytosis) infected by SARS-CoV-2, including the development of post-COVID condition. Data from 1540 patients with CLL infected by SARS-CoV-2 from January 2020 to May 2022 were included in the analysis and assigned to four phases based on cases disposition and SARS-CoV-2 variants emergence. Post-COVID condition was defined according to the WHO criteria. Patients infected during the most recent phases of the pandemic, though carrying a higher comorbidity burden, were less often hospitalized, rarely needed intensive care unit admission, or died compared to patients infected during the initial phases. The 4-month overall survival (OS) improved through the phases, from 68% to 83%, p = .0015. Age, comorbidity, CLL-directed treatment, but not vaccination status, emerged as risk factors for mortality. Among survivors, 6.65% patients had a reinfection, usually milder than the initial one, and 16.5% developed post-COVID condition. The latter was characterized by fatigue, dyspnea, lasting cough, and impaired concentration. Infection severity was the only risk factor for developing post-COVID. The median time to resolution of the post-COVID condition was 4.7 months. OS in patients with CLL improved during the different phases of the pandemic, likely due to the improvement of prophylactic and therapeutic measures against SARS-CoV-2 as well as the emergence of milder variants. However, mortality remained relevant and a significant number of patients developed post-COVID conditions, warranting further investigations

Mitochondria and Energetic Depression in Cell Pathophysiology

Mitochondrial dysfunction is a hallmark of almost all diseases. Acquired or inherited mutations of the mitochondrial genome DNA may give rise to mitochondrial diseases. Another class of disorders, in which mitochondrial impairments are initiated by extramitochondrial factors, includes neurodegenerative diseases and syndromes resulting from typical pathological processes, such as hypoxia/ischemia, inflammation, intoxications, and carcinogenesis. Both classes of diseases lead to cellular energetic depression (CED), which is characterized by decreased cytosolic phosphorylation potential that suppresses the cell’s ability to do work and control the intracellular Ca2+ homeostasis and its redox state. If progressing, CED leads to cell death, whose type is linked to the functional status of the mitochondria. In the case of limited deterioration, when some amounts of ATP can still be generated due to oxidative phosphorylation (OXPHOS), mitochondria launch the apoptotic cell death program by release of cytochrome c. Following pronounced CED, cytoplasmic ATP levels fall below the thresholds required for processing the ATP-dependent apoptotic cascade and the cell dies from necrosis. Both types of death can be grouped together as a mitochondrial cell death (MCD). However, there exist multiple adaptive reactions aimed at protecting cells against CED. In this context, a metabolic shift characterized by suppression of OXPHOS combined with activation of aerobic glycolysis as the main pathway for ATP synthesis (Warburg effect) is of central importance. Whereas this type of adaptation is sufficiently effective to avoid CED and to control the cellular redox state, thereby ensuring the cell survival, it also favors the avoidance of apoptotic cell death. This scenario may underlie uncontrolled cellular proliferation and growth, eventually resulting in carcinogenesis