Expression and purification of active shikimate dehydrogenase from Plasmodium falciparum.

Plasmodium falciparum is known to cause severe malaria, current treatment consists in artemisinin-based combination therapy, but resistance can lead to treatment failure. Knowledge concerning P. falciparum essential proteins can be used for searching new antimalarials, among these a potential candidate is shikimate dehydrogenase (SDH), an enzyme part of the shikimate pathway which is responsible for producing endogenous aromatic amino acids. SDH from P. falciparum (PfSDH) is unexplored by the scientific community, therefore, this study aims to establish the first protocol for active PfSDH expression. Putative PfSDH nucleotide sequence was used to construct an optimized expression vector pET28a+PfSDH inserted in E. coli BL21(DE3). As a result, optimal expression conditions were acquired by varying IPTG and temperature through time. Western Blot analysis was applied to verify appropriate PfSDH expression, solubilization and purification started with lysis followed by two-steps IMAC purification. Enzyme activity was measured spectrophotometrically by NADPH oxidation, optimal PfSDH expression occur at 0.1 mM IPTG for 48 hours growing at 37 °C and shaking at 200 rpm, recombinant PfSDH obtained after purification was soluble, pure and its physiological catalysis was confirmed. Thus, this study describes the first protocol for heterologous expression of PfSDH in soluble and active form.

Epigenetic Mechanisms Histone Deacetylase-Dependent Regulate the Glioblastoma Angiogenic Matrisome and Disrupt Endothelial Cell Behavior In Vitro.

Glioblastoma (GBM) is the most aggressive brain tumor and different efforts have been employed in the search for new drugs and therapeutic protocols for GBM. Epitranscriptomics has shed light on new druggable Epigenetic therapies specifically designed to modulate GBM biology and behavior such as Histone Deacetylase inhibitors (iHDAC). Although the effects of iHDAC on GBM have been largely explored, there is a lack of information on the underlaying mechanisms HDAC-dependent that modulate the repertoire of GBM secreted molecules focusing on the set of Extracellular Matrix (ECM) associated proteins, the Matrisome, that may impact the surrounding tumor microenvironment. To acquire a better comprehension of the impacts of HDAC activity on the GBM Matrisome, we studied the alterations on the Matrisome-associated ECM regulators, Core Matrisome ECM glycoproteins, ECM-affiliated proteins and Proteoglycans upon HDAC inhibition in vitro as well as their relationship with glioma pathophysiological/clinical features and angiogenesis. For this, U87MG GBM cells were treated for with iHDAC or vehicle (control) and the whole secretome was processed by Mass Spectrometry NANOLC-MS/MS. In silico analyses revealed that proteins associated to the Angiogenic Matrisome (AngioMatrix), including Decorin, ADAM10, ADAM12 and ADAM15 were differentially regulated in iHDAC versus control secretome. Interestingly, genes coding for the Matrisome proteins differentially regulated were found mutated in patients and were correlated to glioma pathophysiological/clinical features. In vitro functional assays, using HBMEC endothelial cells exposed to the secretome of control or iHDAC treated GBM cells, coupled to 2D and 3D GBM cell culture system, showed impaired migratory capacity of endothelial cells and disrupted tubulogenesis in a Fibronectin and VEGF independent fashion. Collectively, our study provides understanding of epigenetic mechanisms HDAC-dependent to key Matrisomal proteins that may contribute to identify new druggable Epigenetic therapies or gliomagenesis biomarkers with relevant implications to improve therapeutic protocols for this malignancy.

Applying machine learning random forest (RF) method in predicting the cement products with a co-processing of input materials: Optimizing the hyperparameters.

Co-processing recycled waste during cement production, i.e., using alternative materials such as secondary raw materials or secondary raw fuels, is widely practiced in developed countries. Alternative raw materials or fuels contain high concentrations of heavy metals and other hazardous chemicals, which might lead to the potential for dangerous heavy metals and hazardous chemicals to be transferred to clinker or cement products, resulting in exposure and emissions to people or the environment. Managing input materials and predicting which inputs affect the final concentration is essential to prevent potential hazards. We used the data of six heavy metals by input raw materials and input fuels of cement manufacturers in 2016-2017. The concentrations of Pb and Cu in cement were about 10-200 times and 4 to 200 times higher than other heavy metals (Cr, As, Cd, Hg), respectively. We profiled the influence of heavy metal concentration of each input material using the principal component analysis (PCA), which analyzed the leading causes of each heavy metal. The Random Forest (RF) ensemble model predicted cement heavy metal concentrations according to input materials. In the case of Cu, Cd, and Cr, the training performance showed R square values of 0.71, 0.71, and 0.92, respectively, as a result of predicting the cement heavy metal concentration according to the heavy metal concentration of each cement input material using the RF model, which is a machine learning model. The results of this study show that the RF model can be used to predict the amount and concentration of alternative raw materials and alternative fuels by controlling the concentration of heavy metals in cement through the concentration of heavy metals in the input materials.

Neutrophil to Lymphocyte Ratio and Periprosthetic Joint Infection: A Systematic Review and Meta-Analysis.

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) has shown promising results as a diagnostic tool for periprosthetic joint infection (PJI) after total joint arthroplasty. We conducted a systematic review and meta-analysis to determine the utility of NLR in the diagnosis of PJI. METHODS: We searched PubMed, Scopus, and Web of Science from inception up to 2022 and evaluated the quality of the included literature. RESULTS: Based on the 12 eligible studies, NLR levels were significantly higher in patients who had PJI compared to those who had aseptic loosening (standard mean difference (SMD) = 1.05, 95% Confidence Interval (CI) = 0.71 to 1.40, P < .001). In the subgroup analysis according to type of PJI, NLR levels were significantly higher in patients who had either acute (SMD = 1.04, 95% CI = 0.05 to 2.03, P < .001) or chronic PJI (SMD = 1.08, 95% CI = 0.55 to 1.61, P < .001), compared to those who had aseptic loosening. According to type of arthroplasty, NLR levels were significantly higher in patients who had either total knee arthroplasty (SMD = 1.81, 95% CI = 1.48 to 2.13, P < .001) or total hip arthroplasty (SMD = 1.76, 95% CI = 1.54 to 1.98, P < .001) compared to aseptic loosening. The pooled sensitivity of the 12 studies was 0.73 (95% CI, 0.65 to 0.79), and the pooled specificity was 0.75 (95% CI, 0.71 to 0.78). The pooled positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio of NLR were 2.94 (95% CI = 2.44 to 3.54), 0.35 (95% CI = 0.27 to 0.46), and 8.26 (95% CI = 5.42 to 12.58), respectively. CONCLUSION: In summary, this meta-analysis indicates that NLR is a reliable marker in the diagnosis of PJI.

Identification of Proteomic Biomarkers in Proliferative Verrucous Leukoplakia through Liquid Chromatography With Tandem Mass Spectrometry.

Proliferative verrucous leukoplakia (PVL) is an oral potentially malignant disorder associated with high risk of malignant transformation. Currently, there is no treatment available, and restrictive follow-up of patients is crucial for a better prognosis. Oral leukoplakia (OL) shares some clinical and microscopic features with PVL but exhibits different clinical manifestations and a lower rate of malignant transformation. This study aimed to investigate the proteomic profile of PVL in tissue and saliva samples to identify potential diagnostic biomarkers with therapeutic implications. Tissue and saliva samples obtained from patients with PVL were compared with those from patients with oral OL and controls. Label-free liquid chromatography with tandem mass spectrometry was employed, followed by qualitative and quantitative analyses, to identify differentially expressed proteins. Potential biomarkers were identified and further validated using immunohistochemistry. Staining intensity scan analyses were performed on tissue samples from patients with PVL, patients with OL, and controls from Brazil, Spain, and Finland. The study revealed differences in the immune system, cell cycle, DNA regulation, apoptosis pathways, and the whole proteome of PVL samples. In addition, liquid chromatography with tandem mass spectrometry analyses showed that calreticulin (CALR), receptor of activated protein C kinase 1 (RACK1), and 14-3-3 Tau-protein (YWHAQ) were highly expressed in PVL samples. Immunohistochemistry validation confirmed increased CARL expression in PVL compared with OL. Conversely, RACK1 and YWHA were highly expressed in oral potentially malignant disorder compared to the control group. Furthermore, significant differences in CALR and RACK1 expression were observed in the OL group when comparing samples with and without oral epithelial dysplasia, unlike the PVL. This research provides insights into the molecular mechanisms underlying these conditions and highlights potential targets for future diagnostic and therapeutic approaches.

Crude saliva of Amblyomma cajennense sensu stricto (Acari: Ixodidae) reduces locomotor activity and increases the hemocyte number in the females of Aedes aegypti (Diptera: Culicidae).

Aedes aegypti are vector insects of arboviruses such as dengue, Zika, and chikungunya. All available vector control methods have limited efficacy, highlighting the urgent need to find alternative ones. Evidence shows that arachnids like ticks are sources of biologically active compounds. Moreover, chemical modulation of the locomotor and immune systems of vector insects can be used to control arbovirus transmission. The present study evaluated the effectiveness of crude saliva of female Amblyomma cajennense sensu stricto (s.s.) ticks in reducing locomotor activity and inducing an immune response in Ae. aegypti females. Additionally, the study evaluated the protein constitution of tick saliva. For this purpose, the crude saliva obtained from several semi-engorged A. cajennense females was used. A volume of 0.2 nL of crude tick saliva was administered to mosquitoes by direct intrathoracic microinjection. The effect of the tick's saliva on the locomotor activity of the mosquito was observed using Flybox, a video-automated monitoring system, and the hemolymph hemocyte levels were quantified by reading slides under a light microscope. The protein concentration of the crude tick saliva was 1.27 µg/µL, and its electrophoretic profile indicates the presence of proteins with a molecular weight ranging between ∼17 and 95 kDa. Microplusins, ixodegrins, cystatin, actins, beta-actin, calponin, albumin, alpha-globulins, and hemoglobin were the main proteins identified by proteomics in the saliva of A. cajennense. The microinjected saliva had low toxicity for Ae. aegypti females and significantly reduced their locomotor activity, especially in the transition between the light and dark phases. The crude tick saliva did not change the period and rhythmicity of the circadian cycle. The tick saliva significantly increased the number of hemocytes two days after injection and reduced it after five days. These results suggest that further evaluation of the biological properties of tick saliva proteins against Ae. aegypti would be of interest.

Nitrous oxide-induced subacute combined degeneration of the cord: diagnosis and treatment.

Recreational use of nitrous oxide (N2O) has increased rapidly in recent years and is now the second most commonly used recreational drug among young people in the UK. There has been a corresponding rise in cases of nitrous oxide-induced subacute combined degeneration of the cord (N2O-SACD), a pattern of myeloneuropathy usually associated with severe vitamin B12 deficiency. This can cause serious and permanent disability in young people but, if recognised early, may be effectively treated. All neurologists should be aware of N2O-SACD and its treatment; however, there are currently no agreed guidelines. Based on our experience in East London, an area of high N2O use, we provide practical advice on its recognition, investigation and treatment.

Prognostic indicators and outcomes of hospitalised COVID-19 patients with neurological disease: An individual patient data meta-analysis.

BACKGROUND: Neurological COVID-19 disease has been reported widely, but published studies often lack information on neurological outcomes and prognostic risk factors. We aimed to describe the spectrum of neurological disease in hospitalised COVID-19 patients; characterise clinical outcomes; and investigate factors associated with a poor outcome. METHODS: We conducted an individual patient data (IPD) meta-analysis of hospitalised patients with neurological COVID-19 disease, using standard case definitions. We invited authors of studies from the first pandemic wave, plus clinicians in the Global COVID-Neuro Network with unpublished data, to contribute. We analysed features associated with poor outcome (moderate to severe disability or death, 3 to 6 on the modified Rankin Scale) using multivariable models. RESULTS: We included 83 studies (31 unpublished) providing IPD for 1979 patients with COVID-19 and acute new-onset neurological disease. Encephalopathy (978 [49%] patients) and cerebrovascular events (506 [26%]) were the most common diagnoses. Respiratory and systemic symptoms preceded neurological features in 93% of patients; one third developed neurological disease after hospital admission. A poor outcome was more common in patients with cerebrovascular events (76% [95% CI 67-82]), than encephalopathy (54% [42-65]). Intensive care use was high (38% [35-41]) overall, and also greater in the cerebrovascular patients. In the cerebrovascular, but not encephalopathic patients, risk factors for poor outcome included breathlessness on admission and elevated D-dimer. Overall, 30-day mortality was 30% [27-32]. The hazard of death was comparatively lower for patients in the WHO European region. INTERPRETATION: Neurological COVID-19 disease poses a considerable burden in terms of disease outcomes and use of hospital resources from prolonged intensive care and inpatient admission; preliminary data suggest these may differ according to WHO regions and country income levels. The different risk factors for encephalopathy and stroke suggest different disease mechanisms which may be amenable to intervention, especially in those who develop neurological symptoms after hospital admission.

O-GlcNAcylation protein disruption by Thiamet G promotes changes on the GBM U87-MG cells secretome molecular signature.

Glioblastoma (GBM) is a grade IV glioma highly aggressive and refractory to the therapeutic approaches currently in use. O-GlcNAcylation plays a key role for tumor aggressiveness and progression in different types of cancer; however, experimental evidence of its involvement in GBM are still lacking. Here, we show that O-GlcNAcylation plays a critical role in maintaining the composition of the GBM secretome, whereas inhibition of OGA activity disrupts the intercellular signaling via microvesicles. Using a label-free quantitative proteomics methodology, we identified 51 proteins in the GBM secretome whose abundance was significantly altered by activity inhibition of O-GlcNAcase (iOGA). Among these proteins, we observed that proteins related to proteasome activity and to regulation of immune response in the tumor microenvironment were consistently downregulated in GBM cells upon iOGA. While the proteins IGFBP3, IL-6 and HSPA5 were downregulated in GBM iOGA cells, the protein SQSTM1/p62 was exclusively found in GBM cells under iOGA. These findings were in line with literature evidence on the role of p62/IL-6 signaling axis in suppressing tumor aggressiveness and our experimental evidence showing a decrease in radioresistance potential of these cells. Taken together, our findings provide evidence that OGA activity may regulate the p62 and IL-6 abundance in the GBM secretome. We propose that the assessment of tumor status from the main proteins present in its secretome may contribute to the advancement of diagnostic, prognostic and even therapeutic tools to approach this relevant malignancy.

Add on yoga treatment for negative symptoms of schizophrenia: A multi-centric, randomized controlled trial.

The efficacy of antipsychotic medications in the treatment of negative symptoms of schizophrenia is modest at best. Preliminary studies suggest the beneficial effects of add on Yoga, a traditional Indian practice, in the treatment of schizophrenia. Hence, in this study, we examined the efficacy of yoga as an add-on treatment for negative symptoms of schizophrenia in a randomized, wait-list controlled design from two clinical institutes in south India. 89 patients (age - 34.20 ± 8.06 years; education - 14.22 ± 2.69 years; 28 females) were randomized into the add-on yoga or treatment as usual (TAU - wait-list control) group. Patients had a mean illness duration of 10.97 ± 7.24 years with an age at onset of 23.34 ± 5.81 years. Central block randomization was followed to ensure concealed allocation. Participants randomized to the yoga treatment group attended 12 supervised yoga training sessions over two weeks and practiced yoga sessions at home for the subsequent 10 weeks. 64 patients completed the trial. An intent to treat analysis was conducted with 89 participants using a linear mixed model. Improvement in negative symptoms was our primary outcome measure. The two groups were matched on demographic variables and baseline psychopathology severity. Participants in the add-on yoga group had significantly greater improvement in negative symptoms (SANS baseline: 49.13 ± 2.30; 12-weeks follow up: 31.55 ± 2.53) compared to the TAU group (SANS baseline: 51.22 ± 2.40; 12-weeks follow up: 45.30 ± 2.93; t = 3.36; p = 0.006; Cohen's d-0.65). The current study findings suggest the efficacy of yoga as an add-on treatment for negative symptoms of schizophrenia. The effectiveness of yoga practice as a regular clinical intervention for patients needs to be explored in future studies by integrating yoga services along with other clinical services.

Optimal SARS-CoV-2 vaccine allocation using real-time seroprevalence estimates in Rhode Island and Massachusetts

As three SARS-CoV-2 vaccines come to market in Europe and North America in the winter of 2020-2021, distribution networks will be in a race against a major epidemiological wave of SARS-CoV-2 that began in autumn 2020. Rapid and optimized vaccine allocation is critical during this time. With 95% efficacy reported for two of the vaccines, near-term public health needs require that distribution is prioritized to the elderly, health-care workers, teachers, essential workers, and individuals with co-morbidities putting them at risk of severe clinical progression. Here, we evaluate various age-based vaccine distributions using a validated mathematical model based on current epidemic trends in Rhode Island and Massachusetts. We allow for varying waning efficacy of vaccine-induced immunity, as this has not yet been measured. We account for the fact that known COVID-positive cases may not be included in the first round of vaccination. And, we account for current age-specific immune patterns in both states. We find that allocating a substantial proportion (> 75%) of vaccine supply to individuals over the age of 70 is optimal in terms of reducing total cumulative deaths through mid-2021. As we do not explicitly model other high mortality groups, this result on vaccine allocation applies to all groups at high risk of mortality if infected. Our analysis confirms that for an easily transmissible respiratory virus, allocating a large majority of vaccinations to groups with the highest mortality risk is optimal. Our analysis assumes that health systems during winter 2020-2021 have equal staffing and capacity to previous phases of the SARS-CoV-2 epidemic; we do not consider the effects of understaffed hospitals or unvaccinated medical staff. Vaccinating only seronegative individuals avoids redundancy in vaccine use on individuals that may already be immune, and will result in 1% to 2% reductions in cumulative hospitalizations and deaths by mid-2021. Assuming high vaccination coverage (> 28%) and no major relaxations in distancing, masking, gathering size, or hygiene guidelines between now and spring 2021, our model predicts that a combination of vaccination and population immunity will lead to low or near-zero transmission levels by the second quarter of 2021.

Outcomes of Bilateral Shoulder Arthroplasties: A Comparison of Bilateral Total Shoulder Arthroplasties and Bilateral Reverse Shoulder Arthroplasties.

BACKGROUND: The purpose of this study was to compare outcomes of patients who underwent bilateral total shoulder arthroplasties (TSAs) for osteoarthritis (OA) versus bilateral reverse shoulder arthroplasties (RSAs) for cuff tear arthropathy (CTA). METHODS: Inclusion criteria were patients who underwent bilateral TSAs for OA or bilateral RSAs for CTA with at least 2 years of follow-up. Twenty-six TSA patients (52 shoulders) were matched 2 to 1 with 13 RSA patients (26 shoulders) by sex, age at first surgery, and time between surgeries. Outcomes measured were shoulder range of motion (ROM), complications, and patient-reported scores. RESULTS: Preoperatively, TSA patients had significantly better forward elevation (FE) of both shoulders than RSA patients (dominant side [Dom]: 103° ± 32° vs. 81° ± 31°, p = 0.047; nondominant side [non-Dom]: 111° ± 28° vs. 70° ± 42°, p = 0.005) without significant differences in external (ER) or internal rotation (IR). Postoperatively, TSA patients had significantly better FE (Dom and non-Dom: 156° ± 12°, 156° ± 14° vs. 134° ± 24°, 137° ± 23°; p = 0.006, p = 0.019) and ER (42° ± 11°, 43° ± 10° vs. 24° ± 12°, 25° ± 10°; p < 0.001, p < 0.001) bilaterally and IR of their dominant arm (L1 vs. L4, p = 0.045). TSA patients had significantly better activities of daily living external and internal rotations (ADLEIR) scores (Dom and non-Dom: 35.3 ± 1.0, 35.5 ± 0.9 vs. 32.1 ± 2.4, 32.5 ± 2.2; p = 0.001, p = 0.001), American Shoulder and Elbow Surgeons scores (94.2 ± 8.4, 94.2 ± 8.2 vs. 84.7 ± 10.0, 84.5 ± 8.0; p = 0.015, p = 0.004), and Single Assessment Numerical Evaluation (SANE) scores (93.5 ± 7.6, 93.8 ± 11.8 vs. 80.5 ± 14.2, 82.3 ± 13.1; p = 0.014, p = 0.025), with no significant difference in visual analog scale pain scores (0.4 ± 1.0, 0.3 ± 1.0 vs. 0.7 ± 1.3, 0.8 ± 1.2) bilaterally. CONCLUSIONS: Overall, patients with bilateral TSAs and RSAs exhibited improved ROM and patient-reported outcomes. Those with bilateral TSAs had better functional outcomes than those with bilateral RSAs.

Metabolomic profiling suggests systemic signatures of premature aging induced by Hutchinson-Gilford progeria syndrome.

INTRODUCTION: Hutchinson-Gilford Progeria Syndrome (HGPS) is an extremely rare genetic disorder. HGPS children present a high incidence of cardiovascular complications along with altered metabolic processes and an accelerated aging process. No metabolic biomarker is known and the mechanisms underlying premature aging are not fully understood. OBJECTIVES: The present work aims to evaluate the metabolic alterations in HGPS using high resolution mass spectrometry. METHODS: The present study analyzed plasma from six HGPS patients of both sexes (7.7 ± 1.4 years old; mean ± SD) and eight controls (8.6 ± 2.3 years old) by LC-MS/MS in high-resolution non-targeted metabolomics (Q-Exactive Plus). Targeted metabolomics was used to validate some of the metabolites identified by the non-targeted method in a triple quadrupole (TSQ-Quantiva). RESULTS: We found several endogenous metabolites with statistical differences between control and HGPS children. Multivariate statistical analysis showed a clear separation between groups. Potential novel metabolic biomarkers were identified using the multivariate area under ROC curve (AUROC) based analysis, showing an AUC value higher than 0.80 using only two metabolites, and tending to 1.00 when increasing the number of metabolites in the AUROC model. Taken together, changed metabolic pathways involve sphingolipids, amino acids, and oxidation of fatty acids, among others. CONCLUSION: Our data show significant alterations in cellular energy use and availability, in signal transduction, and lipid metabolites, adding new insights on metabolic alterations associated with premature aging and suggesting novel putative biomarkers.

Outcomes of Bilateral Shoulder Arthroplasties: A Comparison of Bilateral Total Shoulder Arthroplasties and Bilateral Reverse Shoulder Arthroplasties

BACKGROUND: The purpose of this study was to compare outcomes of patients who underwent bilateral total shoulder arthroplasties (TSAs) for osteoarthritis (OA) versus bilateral reverse shoulder arthroplasties (RSAs) for cuff tear arthropathy (CTA). METHODS: Inclusion criteria were patients who underwent bilateral TSAs for OA or bilateral RSAs for CTA with at least 2 years of follow-up. Twenty-six TSA patients (52 shoulders) were matched 2 to 1 with 13 RSA patients (26 shoulders) by sex, age at first surgery, and time between surgeries. Outcomes measured were shoulder range of motion (ROM), complications, and patient-reported scores. RESULTS: Preoperatively, TSA patients had significantly better forward elevation (FE) of both shoulders than RSA patients (dominant side [Dom]: 103° ± 32° vs. 81° ± 31°, p = 0.047; nondominant side [non-Dom]: 111° ± 28° vs. 70° ± 42°, p = 0.005) without significant differences in external (ER) or internal rotation (IR). Postoperatively, TSA patients had significantly better FE (Dom and non-Dom: 156° ± 12°, 156° ± 14° vs. 134° ± 24°, 137° ± 23°; p = 0.006, p = 0.019) and ER (42° ± 11°, 43° ± 10° vs. 24° ± 12°, 25° ± 10°; p < 0.001, p < 0.001) bilaterally and IR of their dominant arm (L1 vs. L4, p = 0.045). TSA patients had significantly better activities of daily living external and internal rotations (ADLEIR) scores (Dom and non-Dom: 35.3 ± 1.0, 35.5 ± 0.9 vs. 32.1 ± 2.4, 32.5 ± 2.2; p = 0.001, p = 0.001), American Shoulder and Elbow Surgeons scores (94.2 ± 8.4, 94.2 ± 8.2 vs. 84.7 ± 10.0, 84.5 ± 8.0; p = 0.015, p = 0.004), and Single Assessment Numerical Evaluation (SANE) scores (93.5 ± 7.6, 93.8 ± 11.8 vs. 80.5 ± 14.2, 82.3 ± 13.1; p = 0.014, p = 0.025), with no significant difference in visual analog scale pain scores (0.4 ± 1.0, 0.3 ± 1.0 vs. 0.7 ± 1.3, 0.8 ± 1.2) bilaterally. CONCLUSIONS: Overall, patients with bilateral TSAs and RSAs exhibited improved ROM and patient-reported outcomes. Those with bilateral TSAs had better functional outcomes than those with bilateral RSAs.

Aging-related compensated hypogonadism: Role of metabolomic analysis in physiopathological and therapeutic evaluation.

Aging is a complex process that increases the risk of chronic disease development. Hormonal and metabolic alterations occur with aging, such as androgen activity decrease. Studies aim to understand the role of testosterone replacement therapy (TRT) in males, however biomarkers and the metabolic responses to TRT are not well characterized. Therefore, the present study investigated TRT effect in young adult and aged rats by metabolomics. Male Wistar rats were divided into four groups: adult and adult + testo (6months), old and old + testo (25-27months). TRT animals received daily testosterone propionate (1 mg/kg/subcutaneous). TRT changed the testicular weight index decrease induced by aging but did not change the body weight and liver weight index. Sera were analyzed by liquid chromatograph high resolution mass spectrometry (LCMS/MS). Testosterone was quantified by target LCMS/MS. A total of 126 metabolites were detected with known identification altered by TRT by non-target metabolomics analysis. Multivariate statistics shows that all groups segregated individually after principal component analysis. The treatment with testosterone induced several metabolic alterations in adult and old rats that were summarized by variable importance on projection score, metabolite interaction and pathway analysis. Aging-related hypogonadism induces a pattern of systemic metabolic alterations that can be partially reversed by TRT, however, this treatment in aged rats induces novel alterations in some metabolites that are possible new targets for monitoring in patients submitted to TRT.

Doping control analysis at the Rio 2016 Olympic and Paralympic Games.

This paper summarises the results obtained from the doping control analyses performed during the Summer XXXI Olympic Games (August 3-21, 2016) and the XV Paralympic Games (September 7-18, 2016). The analyses of all doping control samples were performed at the Brazilian Doping Control Laboratory (LBCD), a World Anti-Doping Agency (WADA)-accredited laboratory located in Rio de Janeiro, Brazil. A new facility at Rio de Janeiro Federal University (UFRJ) was built and fully operated by over 700 professionals, including Brazilian and international scientists, administrative staff, and volunteers. For the Olympic Games, 4913 samples were analysed. In 29 specimens, the presence of a prohibited substance was confirmed, resulting in adverse analytical findings (AAFs). For the Paralympic Games, 1687 samples were analysed, 12 of which were reported as AAFs. For both events, 82.8% of the samples were urine, and 17.2% were blood samples. In total, more than 31 000 analytical procedures were conducted. New WADA technical documents were fully implemented; consequently, state-of-the-art analytical toxicology instrumentation and strategies were applied during the Games, including different types of mass spectrometry (MS) analysers, peptide, and protein detection strategies, endogenous steroid profile measurements, and blood analysis. This enormous investment yielded one of the largest Olympic legacies in Brazil and South America. Copyright © 2017 John Wiley & Sons, Ltd.

Photocatalytic removal of gaseous nitrogen oxides using WO3/TiO2 particles under visible light irradiation: Effect of surface modification.

Photocatalytic nanoparticles have been receiving considerable attention for their potential use in many environmental management applications, including urban air quality control. This paper investigates the performance of surface modified WO3/TiO2 composite particles in removing gaseous nitrogen oxides (NOx) under visible light irradiation. The WO3/TiO2 composite particles were synthesized using a modified wet chemical method with different concentrations of NaOH solution used as a surface modification agent for the host TiO2 particles. The NOx removal efficiency of the WO3/TiO2 particles was evaluated using a lab-scale continuous gas flow photo-reactor with a gas contact time of 1 min. Results showed that surface modification using NaOH can enhance the photocatalytic activity of the WO3/TiO2 particles. The NOx removal efficiency of the surface modified WO3/TiO2 was greater than 90%, while that of WO3/TiO2 particles prepared by the conventional wet chemical method was ∼75%. The enhanced removal efficiency might be attributed to the formation of oxygen vacancies on the TiO2 surface, providing sites for WO3 particles to effectively bind with TiO2. However, excess amount of NaOH >3 M deteriorated the photocatalytic performance due to the increased agglomeration of the host TiO2 particles.

Gender identity and the management of the transgender patient: a guide for non-specialists.

In this review, we introduce the topic of transgender medicine, aimed at the non-specialist clinician working in the UK. Appropriate terminology is provided alongside practical advice on how to appropriately care for transgender people. We offer a brief theoretical discussion on transgenderism and consider how it relates to broader understandings of both gender and disease. In respect to epidemiology, while it is difficult to assess the exact size of the transgender population in the UK, population surveys suggest a prevalence of between 0.2 and 0.6% in adults, with rates of referrals to gender identity clinics in the UK increasing yearly. We outline the legal framework that protects the rights of transgender people, showing that is not legal for physicians to deny transgender people access to services based on their personal beliefs. Being transgender is often, although not always, associated with gender dysphoria, a potentially disabling condition in which the discordance between a person's natal sex (that assigned to them at birth) and gender identity results in distress, with high associated rates of self-harm, suicidality and functional impairment. We show that gender reassignment can be a safe and effective treatment for gender dysphoria with counselling, exogenous hormones and surgery being the mainstay of treatment. The role of the general practitioner in the management of transgender patients is discussed and we consider whether hormone therapy should be initiated in primary care in the absence of specialist advice, as is suggested by recent General Medical Council guidance.