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The variety of available mitochondrial quantification tools makes it difficult to select the most reliable and accurate quantification tool. Here, we performed elaborate analyses on five open source ImageJ tools. Excessive clustering of mitochondrial structures was observed in four tools, caused by the global thresholding applied by these tools. The Mitochondrial Analyzer, which uses adaptive thresholding, outperformed the other examined tools, with accurate structural segregation and identification. Additionally, we showed that the Mitochondrial Analyzer successfully identifies mitochondrial morphology differences. Based on the observed performance, we consider the Mitochondrial Analyzer the best open source tool for mitochondrial network morphology quantification.Mitochondria fuel placental activity, with mitochondrial dysfunction implicated in several perinatal complications. We investigated placental mtDNA mutational load using NextGen sequencing in relation to birthweight and gestational length among 358 mother-newborn pairs. We found that higher heteroplasmy, especially in the hypervariable displacement loop region, was associated with shorter gestational length. Results were similar among male and female pregnancies, but stronger in magnitude among females. With regard to growth, we observed that higher mutational load was associated with lower birthweight-for-gestational age (BWGA) among females, but higher BWGA among males. These findings support potential sex-differential fetal biological strategies for coping with increased heteroplasmies.Protein aggregation has two aspects, namely, mechanistic and kinetics. Understanding protein aggregation kinetics is critical for prediction of progression of diseases caused by amyloidosis, accumulation of aggregates in biotherapeutics during storage and engineering commercial nano-biomaterials. In this work, we have collected experimentally determined absolute protein aggregation rates and developed an SVM based regression model to predict absolute rates of protein and peptide aggregation near-physiological conditions. The regression model achieved a correlation coefficient of 0.72 with MAE of 0.91 (natural log of kapp, where kapp is in hour-1) using leave-one-out cross-validation on a dataset of 82 non-redundant proteins/peptides. The model accounts for the experimental conditions (such as temperature, pH, ionic and protein concentration) and sequence-based properties. The amino acid sequence features revealed by this model as being important for aggregation kinetics, are also associated with the aggregation mechanism. In particular, inherent aggregation propensity of the protein/peptide sequence and number of aggregation prone regions (APRs) unpunctuated by the gatekeeping residues, were found to play important roles in the prediction of the absolute aggregation rates. This analysis shows that mechanism and kinetics of protein aggregation are coupled via common sequence attributes. The aggregation kinetic prediction method developed in this work is available at https//web.iitm.ac.in/bioinfo2/absolurate-pred/index.html.
Primary dysmenorrhea affects 60% of adolescent girls between 14 and 19 years of age and higher rates of depression and absenteeism are found in these young women. Having developed a sense of coherence (SOC) protects against depression associated with and improves the experience of primary dysmenorrhea. The aim of the study was to describe the association between primary dysmenorrhea and SOC. MéTHODS A multicentric and cross-sectional study was performed on 247 high school girls from Finistère (France).
Sixty point seven per cent of high school girls suffer from primary dysmenorrhea average VAS greater than or equal to 4 out of 10 with an improvement in pain by analgesics if severe pain (greater than 7 out of 10) to eliminate secondary dysmenorrhea (3.6% suspected). Thirty five point six per cent do not present dysmenorrhea (VAS between 0 and 3). This study shows that having a high SOC reduces menstrual pain (P=0.014). The main treatments used are not those recommended by Clinical practice guidelines.
Interventions based on Comprehensive Sexuality Education, medical consultations respecting salutogenic model would provide a better quality of life for adolescent girls by promoting the development of psycho-social skills.
Interventions based on Comprehensive Sexuality Education, medical consultations respecting salutogenic model would provide a better quality of life for adolescent girls by promoting the development of psycho-social skills.Urban sewage is a source of major contamination in aquatic systems and contributes to environmental and human health disturbances. This study investigates the effects of sewage-polluted waters from Iguaçu River on the health of juvenile Oreochromis niloticus. Two hundred four specimens were exposed to riverine water in four groups no diluted, 25 and 50 % diluted water and a control group without tested water for 72 days. Biological samples were obtained for histopathological, neurotoxicity, antioxidant defenses, genotoxicity, metallothionines expression and polycyclic aromatic hydrocarbons (PAHs) metabolites. The results showed histopathological alterations in liver and gills, genotoxic alteration in erythrocytes, reduction of acetylcholinesterase activity in brain and muscle, activation of antioxidant defenses in the liver, recruitment of metals by metallothionein and the detection of PAHs metabolites in bile. These results demonstrate that juveniles of O. niloticus are susceptible to Iguaçu River exposure water and they can be used as indicator of water quality.
The rate and trend of transfusion transmissible infections (TTIs) in blood donations from 2012 to 2017 at the Bamenda Regional Hospital Blood Service (BRHBS), Cameroon was assessed.
A six-year retrospective study was conducted by reviewing the records of donors. Blood was screened for HIV, hepatitis B, hepatitis C and syphilis. Data was analyzed using IBM SPSS Statistics version 21. Differences in seropositivity rates for the four TTIs were analyzed using Chi
test or Fisher's exact test where appropriate. Associations between sociodemographic characteristics and the TTIs markers were assessed using multiple logistic regression analysis.
A total of 12,115 blood donations was included in the study and of these, the overall seropositivity rate of the four conventional TTIs markers was 10.5% (n=1,273). Of the seropositive cases, 23.8% (n=303) showed reactivity with at least two of the markers combined. When the markers were assessed individually, HBsAg recorded the highest seropositivity rate (4.7%), followed by anti-HIV and anti-syphilis (2.2%), and then by anti-HCV (1.7%). A significant decrease in the trend of the combined serological markers, HBsAg and anti-syphilis was observed over the years (P≤0.05).
There is a decrease in seropositivity rates of TTIs markers in this blood service. Ongoing efforts toward the prevention of these infections is encouraged and should be intensified to improve blood safety.
There is a decrease in seropositivity rates of TTIs markers in this blood service. Ongoing efforts toward the prevention of these infections is encouraged and should be intensified to improve blood safety.DARC (Detection of Apoptosing Retinal Cells) is a retinal imaging technology that has been developed within the last 2 decades from basic laboratory science to Phase 2 clinical trials. It uses ANX776 (fluorescently labelled Annexin A5) to identify stressed and apoptotic cells in the living eye. During its development, DARC has undergone biochemistry optimisation, scale-up and GMP manufacture and extensive preclinical evaluation. NSC-724772 Initially tested in preclinical glaucoma and optic neuropathy models, it has also been investigated in Alzheimer, Parkinson's and Diabetic models, and used to assess efficacy of therapies. Progression to clinical trials has not been speedy. Intravenous ANX776 has to date been found to be safe and well-tolerated in 129 patients, including 16 from Phase 1 and 113 from Phase 2. Results on glaucoma and AMD patients have been recently published, and suggest DARC with an AI-aided algorithm can be used to predict disease activity. New analyses of DARC in GA prediction are reported here. Although further studies are needed to validate these findings, it appears there is potential of the technology to be used as a biomarker. Much larger clinical studies will be needed before it can be considered as a diagnostic, although the relatively non-invasive nature of the nasal as opposed to intravenous administration would widen its acceptability in the future as a screening tool. This review describes DARC development and its progression into Phase 2 clinical trials from lab-based research. It discusses hypotheses, potential challenges, and regulatory hurdles in translating technology.Tractional deformations of the fovea mainly arise from an anomalous posterior vitreous detachment and contraction of epiretinal membranes, and also occur in eyes with cystoid macular edema or high myopia. Traction to the fovea may cause partial- and full-thickness macular defects. Partial-thickness defects are foveal pseudocysts, macular pseudoholes, and tractional, degenerative, and outer lamellar holes. The morphology of the foveal defects can be partly explained by the shape of Müller cells and the location of tissue layer interfaces of low mechanical stability. Because Müller cells and astrocytes provide the structural scaffold of the fovea, they are active players in mediating tractional alterations of the fovea, in protecting the fovea from such alterations, and in the regeneration of the foveal structure. Tractional and degenerative lamellar holes are characterized by a disruption of the Müller cell cone in the foveola. After detachment or disruption of the cone, Müller cells of the foveal walls support the structural stability of the foveal center. After tractional elevation of the inner layers of the foveal walls, possibly resulting in foveoschisis, Müller cells transmit tractional forces from the inner to the outer retina leading to central photoreceptor layer defects and a detachment of the neuroretina from the retinal pigment epithelium. This mechanism plays a role in the widening of outer lameller and full-thickness macular holes, and contributes to visual impairment in eyes with macular disorders caused by conractile epiretinal membranes. Müller cells of the foveal walls may seal holes in the outer fovea and mediate the regeneration of the fovea after closure of full-thickness holes. The latter is mediated by the formation of temporary glial scars whereas persistent glial scars impede regular foveal regeneration. Further research is required to improve our understanding of the roles of glial cells in the pathogenesis and healing of tractional macular disorders.
The dynamics of viral reservoir decay and naïve CD4 T-cell recovery between immunological non-responders (INR) and complete responders (CR) during long-term antiretroviral treatment (ART) are not fully known.
Twenty-eight chronic HIV-infected individuals on 5-year ART were divided into two groups INR (CD4 counts ≤350 cells/μL, n=13) and CR (CD4 counts ≥500 cells/μL, n=15). The levels of HIV DNA and cell-associated HIV RNA (CA-RNA), CD4 counts, naïve CD4 counts and their correlations were analyzed at baseline, years 1, 3 and 5 of ART between the two groups. Expression of PD-1 on CD4 T-cells was quantified by flow cytometry. Linear mixed effect models were used to estimate the change procession in repeated measurements over 5years. Slopes of the above-mentioned indicators were estimated using participant-specific linear regressions, respectively.
INR maintained higher levels of HIV DNA and CA-RNA with higher percentages of PD-1
CD4 T-cells compared with CR during 5-year ART, concurrent with lower naïve CD4 T-cells.
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