Aneuploidy facilitates dysplastic and tumorigenic phenotypes in the Drosophila gut

Aneuploidy has been strongly linked to cancer development, and published evidence has suggested that aneuploidy can have an oncogenic or a tumor suppressor role depending on the tissue context. Using the Drosophila midgut as a model, we have recently described that adult intestinal stem cells (ISCs), do not activate programmed cell death upon aneuploidy induction, leading to an increase in ISC proliferation rate, and tissue dysplasia. How aneuploidy impacts ISCs in intestinal tumorigenic models remains to be investigated, and it represents a very important biological question to address since data from multiple in vivo models suggests that the cellular impact of aneuploidy is highly dependent on the cellular and tissue context. Using manipulation of different genetic pathways such as EGFR, JAK-STAT and Notch that cause dysplastic phenotypes in the Drosophila gut, we found that concomitant aneuploidy induction by impairment of the Spindle Assembly Checkpoint (SAC) consistently leads to a more severe progression of intestinal dysplasia or tumorigenesis. This is characterized by an accumulation of progenitor cells, high tissue cell density and higher stem cell proliferation rates, revealing an additive or synergistic effect depending on the misregulated pathway in which aneuploidy was induced. Thus, our data suggests that in the Drosophila gut, both dysplasia and tumorigenic phenotypes can be fueled by inducing genomic instability of resident stem cells.This work was funded by National Funds through FCT – Fundação para a Ciência e a Tecnologia, I.P., under the project UIDB/04293/2020

Ocular neuromyotonia

Ocular neuromyotonia is a rare, albeit treatable, ocular motor disorder, characterised by recurrent brief episodes of diplopia due to tonic extraocular muscle contraction. Ephaptic transmission in a chronically damaged ocular motor nerve is the possible underlying mechanism. It usually improves with carbamazepine. A 53-year-old woman presented with a 4-month history of recurrent episodes of binocular vertical diplopia (up to 40/day), either spontaneously or after sustained downward gaze. Between episodes she had a mild left fourth nerve palsy. Sustained downward gaze consistently triggered downward left eye tonic deviation, lasting around 1 min. MR scan of the brain was normal. She improved on starting carbamazepine but developed a rash that necessitated stopping the drug. Switching to lacosamide controlled her symptoms.info:eu-repo/semantics/publishedVersio

Evidences of the fractional kinetics in temperature region: Evolution of extreme points in ibuprofen

Based on a new approach presented in detail in this paper one can find new evidences of existence of the fractional kinetics not only in the frequency range. One can find rather general principles of detection of different collective motions in temperature region. These principles can be expressed in terms of an algorithm (defined in the paper as an approach). This approach includes some steps that help to separate a couple of the neighboring collective motions (expressed in the frequency range as a linear combination of two power-law exponents) from each other and establish the temperature evolution of the extreme point that follows to the generalized Vogel-Fulcher-Tamman (VFT)-equation. This experimentally confirmed fact gives new evidences for supporting of the theory of dielectric relaxation based on the fractional kinetics on the frequency/temperature domain. As an example for verification of this new approach the ibuprofen complex permittivity data measured in the wide frequency/temperature range were chosen. The reason of such selection was the following. It helps to compare the conventional study of this complex substance recently published in [1] and use possibilities of the developed approach that can add some new features to the picture obtained in the frame of the conventional treatment. We suppose that possibilities presented by new approach will be extremely useful for detection of different collective motions in other substances studied by the method of broadband dielectric spectroscopy (BDS). © 2009 Elsevier B.V. All rights reserved

High-risk features and predictors of unexplained syncope in the young SCD-SOS cohort

Introduction: The Sudden Cardiac Death-Screening of Risk FactOrS survey included a 12-lead ECG plus a digital-based questionnaire and aimed to screen for warning signs of diseases that may course with sudden cardiac death in children and young adults. We aimed to estimate the prevalence of unexplained syncope (US) and characterize its high-risk features and predictors in this cohort. // Methods &Results: We determined the most probable etiology of transient loss of consciousness (TLOC) episodes based on clinical criteria. US was an exclusion diagnosis and we analyzed its potential clinical and ECG predictors. Among 11,878 individuals, with a mean age of 21±6 (range 6-40) years-old, the cumulative incidence of TLOC was 26.5%, 76.2% corresponding to females. Reflex syncope was present in 66.4%, orthostatic hypotension in 8.2% and 14.8% of the individuals had US. Unexplained syncope was independently associated with age <18years-old (OR 1.695; 95%CI 1.26-2.29,p=0.001), male gender (OR 1.642; 95%CI 1.22-2.22,p=0.001), participation in competitive sports (OR 1.644;95%CI 1.01-2.66,p=0.043), syncope during exertion and/or palpitations preceding syncope (OR 2.556; 95%CI 1.92-3.40,p<0.001), syncope after exertion (OR 2.662; 95%CI 1.73-4.10,p<0.001), fever context (OR 9.606; 95%CI 4.13-22.34,p<0.001), isolated previous syncopal episode (OR 2.780; 95%CI 0.2.06-3.75,p<0.001) and history of palpitations requiring medical care (OR 1.945; 95%CI 1.14-3.31,p=0.014). We found no ECG predictors of US in this population. // Conclusions: The cumulative incidence of TLOC in children and young adults is high and remains unexplained in an important proportion of individuals. We identified eight clinical characteristics that may be useful for the risk stratification of individuals evaluated in a non-acute setting

Next generation sequencing techniques in neurological diseases: redefining clinical and molecular associations.

The development of next-generation sequencing technologies has allowed for the identification of several new genes and genetic factors in human genetics. Common results from the application of these technologies have revealed unexpected presentations for mutations in known disease genes. In this review, we summarize the major contributions of exome sequencing to the study of neurodegenerative disorders and other neurological conditions and discuss the interface between Mendelian and complex neurological diseases with a particular focus on pleiotropic events

Technological and Sustainable Perception on the Advancements of Prefabrication in Construction Industry

The construction industry has experienced phenomenal growth because of technological advancements in the past couple of decades. Prefabrication constitutes a sizeable share of this industry and is being adopted all over the world. The method of casting construction elements in a controlled environment and assembling them on-site has revolutionised the industry. Research on various aspects of the technology is ongoing around the world, and an impressive number of articles have been published. However, the prefab technology, materials used, and terminology have varied across locations, which may have hindered the method’s wider acceptability. By evaluating technical articles published between 1991 and 2022, this report analyses the present body of knowledge regarding prefab technology, its evolution, sustainability, and stakeholder views. This technology effectively contributes around 40% in time saving, 27% in cost reduction, 30% in reduced carbon emissions, and 84% in on-site wastage reduction. It also increases quality, gives a dependable alternative for meeting mass construction targets, is energy efficient, and provides environmentally conscious options. This paper contributes to the body of knowledge by providing a snapshot of the prefab industry spanning three decades, detailing a wide range of factors affecting the industry

O Valor Prognóstico do Ponto Ótimo Cardiorrespiratório após Prova de Esforço Cardiorrespiratória Submáxima na Insuficiência Cardíaca

Introduction: Peak oxygen consumption (pVO2) is a key parameter for assessing the prognosis of heart failure with reduced ejection fraction (HFrEF). However, it is less reliable when the cardiopulmonary exercise test (CPET) is not maximal. Objective: To compare the prognostic power of various exercise parameters in submaximal CPET. Methods: Adult patients with HFrEF undergoing CPET in a tertiary center were prospectively assessed. Submaximal CPET was defined as a respiratory exchange ratio ≤1.10. Patients were followed for one year for the primary endpoint of cardiac death and urgent heart transplantation (HT). Various CPET parameters were analyzed as potential predictors of the combined endpoint and their prognostic power (area under the curve [AUC]) was compared using the Hanley-McNeil test. Results: CPET was performed in 442 HFrEF patients (mean age 56±12 years, 80% male), of whom 290 (66%) had a submaximal CPET. Seventeen patients (6%) reached the primary endpoint. The cardiorespiratory optimal point (COP) had the highest AUC value (0.989, p<0.001), and significantly higher prognostic power than other tested parameters, with pVO2 presenting an AUC of 0.753 (p=0.001). COP ≥36 had significantly lower survival free of HT during follow-up (p<0.001) and presented a sensitivity of 100% and a specificity of 89% for the primary endpoint. Conclusion: COP had the highest prognostic power of all parameters analyzed in a submaximal CPET. This parameter can help stratify HFrEF patients who are physiologically unable to reach a maximal level of exercise.info:eu-repo/semantics/publishedVersio

Biological treatment of effluent containing textile dyes

Colour removal of textile dyes from effluent was evaluated using a laboratory upflow anaerobic sludge blanket reactor. Several commercial dyes were selected to study the effect of dye structure on colour removal. The anaerobic reactor was fed with glucose, an easily biodegradable organic matter and selected individual dyes. Results show that some of the dyes are readily reduced under anaerobic conditions even at high concentration of 700 mg/l. The average removal efficiency for acid dyes using this method was between 80 and 90% and that observed for the direct used was 81%. Laboratory experiments using the anaerobic reactor with disperse dyes, such as an anthraquinone based dye, were unsuccessful even at low concentrations of 35 mg/l. Additional experiments were conducted to evaluate the toxicity of a selected disperse dye to an anaerobic environment. Results indicate that the purified dye is more toxic to the biomass than the commercial one

Life Cycle Assessment of a Sustainable Prefabricated Housing System: A Cradle-to-Site Approach Based on a Small-Scale Experimental Model

India is in need of rapid construction technology with sustainability and environmentally friendly aspects. Prefabrication is a well-known technique that lowers carbon emissions and reduces environmental impacts. Life cycle assessment (LCA) evaluates these impacts of developed product/process. A new-age construction product was designed from a locally available agro-industrial waste called co-fired ash (CFA). Expanded polystyrene beads, fly ash, and crushed sand were also used in designing lightweight (LW) sustainable prefabricated panels. The effect of incorporating sustainable alternates into the mix designs is to be studied. An experimental small-scale model house was erected and LCA for the same was carried out with cradle-to-site approach. Based on the inventory, the environmental impact was assessed for four different indicators: acidification potential (AP), eutrophication potential (EP), global warming potential (GWP), and ozone depletion potential (ODP) were evaluated. Carbon emissions of the respective CFA-based concrete and LW prefabricated mix were found to be 0.162 kgCO2e/kg and 0.268 kgCO2e/kg, respectively. The impact of energy required during production, transport, and indirect emissions were found to contribute 3%, 3%, and 94%, respectively, to the proposed prefabricated system. Comprehensively, the phase involving mixing of LW mix contributed majorly towards all the impact indicators followed by mould preparation and material transport. The presented data helps the academia to quantify and recognise the possibilities to enhance their products’ performance

An AARS variant as the likely cause of Swedish type hereditary diffuse leukoencephalopathy with spheroids

Swedish type Hereditary Diffuse Leukoencephalopathy with Spheroids (HDLS-S) is a severe adult-onset leukoencephalopathy with the histopathological hallmark of neuraxonal degeneration with spheroids, described in a large family with a dominant inheritance pattern. The initial stage of the disease is dominated by frontal lobe symptoms that develop into a rapidly advancing encephalopathy with pyramidal, deep sensory, extrapyramidal and optic tract symptoms. Median survival is less than 10 years. Recently, pathogenic mutations in CSF1R were reported in a clinically and histologically similar leukoencephalopathy segregating in several families. Still, the cause of HDLS-S remained elusive since its initial description in 1984, with no CSF1R mutations identified in the family. Here we update the original findings associated with HDLS-S after a systematic and recent assessment of several family members. We also report the results from exome sequencing analyses indicating the p.Cys152Phe variant in the alanyl tRNA synthetase (AARS) gene as the probable cause of this disease. The variant affects an amino acid located in the aminoacylation domain of the protein and does not cause differences in splicing or expression in the brain. Brain pathology in one case after 10 years of disease duration showed the end stage of the disease to be characterized by widespread liquefaction of the white matter leaving only some macrophages and glial cells behind the centrifugally progressing front. These results point to AARS as a candidate gene for rapidly progressing adult-onset CSF1R-negative leukoencephalopathies