Histopathological Study of Pure Primary Nephrotic Syndrome in Adolescents and Young Moroccan Adults

Introduction: The primary nephrotic syndrome (PNS) is the most common glomerular nephropathy in children. Its diagnosis and management don’t require histopathological study. It occurs mainly in the form of minimal glomerular lesion and in most cases respond to corticosteroids. The literature on histological lesions of pure PNS in adolescents and young adults is rare. Thus, there are no criteria or recommendations regarding the indications for renal biopsy in patients aged 12-18 years. Methods: This is a retrospective study in which we encountered a total of 386 patients aged 12 to 25 years who were admitted and biopsied at the Nephrology Unit of Ibn Roshd Hospital in Casablanca during the period from January 1st, 2000 to September 30th, 2009 . Patients with pure PNS were 77 (20%), all were included in this study. Results: The average incidence of pure PNS was 7.7 cases per year. The study included 47 males (61%) and 30 females (39%). Patients were sent from all parts of Morocco and the average length of hospital stay was four days. Renal biopsies showed the following morphological lesions: minimal glomerular lesions in 61 cases (79.20%), focal segmental hyalinosis in 7 cases (9.10%), extramembranous glomerulonephritis in 7 cases (9.10%) and 2 cases of renal amyloidosis (2.6%). Conclusion: The minimal glomerular lesions were the most common cause of pure primary nephrotic syndrome in patients aged 12-25 years. Initial renal biopsy may not be indicated in this age group, and an empiric therapeutic trial with corticosteroids may be initially considered.Keywords: Glomerular Disease; Children; Nephrotic Syndrome; Renal Biops

Earth-observation-based estimation and forecasting of particulate matter impact on solar energy in Egypt

This study estimates the impact of dust aerosols on surface solar radiation and solar energy in Egypt based on Earth Observation (EO) related techniques. For this purpose, we exploited the synergy of monthly mean and daily post processed satellite remote sensing observations from the MODerate resolution Imaging Spectroradiometer (MODIS), radiative transfer model (RTM) simulations utilizing machine learning, in conjunction with 1-day forecasts from the Copernicus Atmosphere Monitoring Service (CAMS). As cloudy conditions in this region are rare, aerosols in particular dust, are the most common sources of solar irradiance attenuation, causing performance issues in the photovoltaic (PV) and concentrated solar power (CSP) plant installations. The proposed EO-based methodology is based on the solar energy nowcasting system (SENSE) that quantifies the impact of aerosol and dust on solar energy potential by using the aerosol optical depth (AOD) in terms of climatological values and day-to-day monitoring and forecasting variability from MODIS and CAMS, respectively. The forecast accuracy was evaluated at various locations in Egypt with substantial PV and CSP capacity installed and found to be within 5–12% of that obtained from the satellite observations, highlighting the ability to use such modelling approaches for solar energy management and planning (M&P). Particulate matter resulted in attenuation by up to 64–107 kWh/m2 for global horizontal irradiance (GHI) and 192–329 kWh/m2 for direct normal irradiance (DNI) annually. This energy reduction is climatologically distributed between 0.7% and 12.9% in GHI and 2.9% to 41% in DNI with the maximum values observed in spring following the frequent dust activity of Khamaseen. Under extreme dust conditions the AOD is able to exceed 3.5 resulting in daily energy losses of more than 4 kWh/m2 for a 10 MW system. Such reductions are able to cause financial losses that exceed the daily revenue values. This work aims to show EO capabilities and techniques to be incorporated and utilized in solar energy studies and applications in sun-privileged locations with permanent aerosol sources such as Egypt

PRUNE is crucial for normal brain development and mutated in microcephaly with neurodevelopmental impairment.

PRUNE is a member of the DHH (Asp-His-His) phosphoesterase protein superfamily of molecules important for cell motility, and implicated in cancer progression. Here we investigated multiple families from Oman, India, Iran and Italy with individuals affected by a new autosomal recessive neurodevelopmental and degenerative disorder in which the cardinal features include primary microcephaly and profound global developmental delay. Our genetic studies identified biallelic mutations of PRUNE1 as responsible. Our functional assays of disease-associated variant alleles revealed impaired microtubule polymerization, as well as cell migration and proliferation properties, of mutant PRUNE. Additionally, our studies also highlight a potential new role for PRUNE during microtubule polymerization, which is essential for the cytoskeletal rearrangements that occur during cellular division and proliferation. Together these studies define PRUNE as a molecule fundamental for normal human cortical development and define cellular and clinical consequences associated with PRUNE mutation

The Immune Cell Composition in Barrett's Metaplastic Tissue Resembles That in Normal Duodenal Tissue

BACKGROUND AND OBJECTIVE: Barrett's esophagus (BE) is characterized by the transition of squamous epithelium into columnar epithelium with intestinal metaplasia. The increased number and types of immune cells in BE have been indicated to be due to a Th2-type inflammatory process. We tested the alternative hypothesis that the abundance of T-cells in BE is caused by a homing mechanism that is found in the duodenum. PATIENTS AND METHODS: Biopsies from BE and duodenal tissue from 30 BE patients and duodenal tissue from 18 controls were characterized by immmunohistochemistry for the presence of T-cells and eosinophils(eos). Ex vivo expanded T-cells were further phenotyped by multicolor analysis using flowcytometry. RESULTS: The high percentage of CD4(+)-T cells (69±3% (mean±SEM/n = 17, by flowcytometry)), measured by flowcytometry and immunohistochemistry, and the presence of non-activated eosinophils found in BE by immunohistochemical staining, were not different from that found in duodenal tissue. Expanded lymphocytes from these tissues had a similar phenotype, characterized by a comparable but low percentage of αE(CD103) positive CD4(+)cells (44±5% in BE, 43±4% in duodenum of BE and 34±7% in duodenum of controls) and a similar percentage of granzyme-B(+)CD8(+) cells(44±5% in BE, 33±6% in duodenum of BE and 36±7% in duodenum of controls). In addition, a similar percentage of α4β7(+) T-lymphocytes (63±5% in BE, 58±5% in duodenum of BE and 62±8% in duodenum of controls) was found. Finally, mRNA expression of the ligand for α4β7, MAdCAM-1, was also similar in BE and duodenal tissue. No evidence for a Th2-response was found as almost no IL-4(+)-T-cells were seen. CONCLUSION: The immune cell composition (lymphocytes and eosinophils) and expression of intestinal adhesion molecule MAdCAM-1 is similar in BE and duodenum. This supports the hypothesis that homing of lymphocytes to BE tissue is mainly caused by intestinal homing signals rather than to an active inflammatory response

Prognostic significance of a complete pathological response after induction chemotherapy in operable breast cancer

Only a few papers have been published concerning the incidence and outcome of patients with a pathological complete response after cytotoxic treatment in breast cancer. The purpose of this retrospective study was to assess the outcome of patients found to have a pathological complete response in both the breast and axillary lymph nodes after neoadjuvant chemotherapy for operable breast cancer. Our goal was also to determine whether the residual pathological size of the tumour in breast could be correlated with pathological node status. Between 1982 and 2000, 451 consecutive patients were registered into five prospective phase II trials. After six cycles, 396 patients underwent surgery with axillary dissection for 277 patients (69.9%). Pathological response was evaluated according to the Chevallier's classification. At a median follow-up of 8 years, survival was analysed as a function of pathological response. A pathological complete response rate was obtained in 60 patients (15.2%) after induction chemotherapy. Breast tumour persistence was significantly related to positive axillary nodes (P=5.10−6). At 15 years, overall survival and disease-free survival rates were significantly higher in the group who had a pathological complete response than in the group who had less than a pathological complete response (P=0.047 and P=0.024, respectively). In the absence of pathological complete response and furthermore when there is a notable remaining pathological disease, axillary dissection is still important to determine a major prognostic factor and subsequently, a second non cross resistant adjuvant regimen or high dose chemotherapy could lead to a survival benefit

Long non-coding RNA RAMS11 promotes metastatic colorectal cancer progression

Colorectal cancer (CRC) is the most common gastrointestinal malignancy in the U.S.A. and approximately 50% of patients develop metastatic disease (mCRC). Despite our understanding of long non-coding RNAs (lncRNAs) in primary colon cancer, their role in mCRC and treatment resistance remains poorly characterized. Therefore, through transcriptome sequencing of normal, primary, and distant mCRC tissues we find 148 differentially expressed RNAs Associated with Metastasis (RAMS). We prioritize RAMS11 due to its association with poor disease-free survival and promotion of aggressive phenotypes in vitro and in vivo. A FDA-approved drug high-throughput viability assay shows that elevated RAMS11 expression increases resistance to topoisomerase inhibitors. Subsequent experiments demonstrate RAMS11-dependent recruitment of Chromobox protein 4 (CBX4) transcriptionally activates Topoisomerase II alpha (TOP2α). Overall, recent clinical trials using topoisomerase inhibitors coupled with our findings of RAMS11-dependent regulation of TOP2α supports the potential use of RAMS11 as a biomarker and therapeutic target for mCRC

Changes in Body Weight and Psychotropic Drugs: A Systematic Synthesis of the Literature

<div><h3>Introduction</h3><p>Psychotropic medication use is associated with weight gain. While there are studies and reviews comparing weight gain for psychotropics within some classes, clinicians frequently use drugs from different classes to treat psychiatric disorders.</p> <h3>Objective</h3><p>To undertake a systematic review of all classes of psychotropics to provide an all encompassing evidence-based tool that would allow clinicians to determine the risks of weight gain in making both intra-class and interclass choices of psychotropics.</p> <h3>Methodology and Results</h3><p>We developed a novel hierarchical search strategy that made use of systematic reviews that were already available. When such evidence was not available we went on to evaluate randomly controlled trials, followed by cohort and other clinical trials, narrative reviews, and, where necessary, clinical opinion and anecdotal evidence. The data from the publication with the highest level of evidence based on our hierarchical classification was presented. Recommendations from an expert panel supplemented the evidence used to rank these drugs within their respective classes. Approximately 9500 articles were identified in our literature search of which 666 citations were retrieved. We were able to rank most of the psychotropics based on the available evidence and recommendations from subject matter experts. There were few discrepancies between published evidence and the expert panel in ranking these drugs.</p> <h3>Conclusion</h3><p>Potential for weight gain is an important consideration in choice of any psychotropic. This tool will help clinicians select psychotropics on a case-by-case basis in order to minimize the impact of weight gain when making both intra-class and interclass choices.</p> </div