Long-term Insights: Histopathological Assessment of Polyurethane Implant Capsules Over 24 Years.

BACKGROUND: Polyurethane (PU)-coated breast implants are known for their strong integration into breast tissue and the formation of capsules around them. However, capsular contracture can pose both aesthetic and clinical challenges. OBJECTIVES: The objectives of this study were to analyze the biological and morphological characteristics of the capsular tissue surrounding PU-coated implants, irrespective of their contracture status, and to assess their potential suitability as a flap in revisional breast surgery for capsular contracture. METHODS: A total of 23 tissue samples were harvested from the capsules surrounding PU-coated breast implants in 12 female patients during replacement or revisional surgery. We evaluated collagen abundance, cellular and vascular density, inflammation, collagen band types and alignment, synovial metaplasia, capsule thickness, and the expression of inflammatory biomarkers and myofibroblasts with immunohistochemical techniques. Scanning electron microscopy was employed to assess implant surface characteristics over time. RESULTS: We found a significant association of capsule contraction with longer implantation durations and greater implant surface roughness (P = .018 and P = .033, respectively). Synovial metaplasia was significantly more frequent in noncontracted capsules (P = .0049). Both capsule types consisted of paucicellular, type I collagen-rich compact fibrous tissue with low vascularization. There was a marked reduction in inflammatory cells within the foreign body granuloma. The expression of inflammatory biomarkers in the capsular tissue was negligible. CONCLUSIONS: Given the reduced levels of inflammatory and vascular components within the dense, fibrous capsular tissue, we consider them to be viable alternatives for capsular flaps in revisional surgery. This strategy has the potential to mimic the reconstruction achieved with acellular dermal matrix.

Temporal trends of persistent organic pollutant contamination in Franciscana dolphins from the Southwestern Atlantic.

Persistent organic pollutants (POPs) were analyzed in 136 blubber samples of Franciscana dolphins from Brazil (Pontoporia blainvillei), which is the most threatened dolphin in the Southwestern Atlantic. The dolphins were caught by the fishery fleet and collected from 2000 to 2018 in three regions of São Paulo state: northern São Paulo (SPN), central São Paulo (SPC), and southern São Paulo (SPS). The POPs analyzed in this study were polychlorinated biphenyls (PCBs), dichlorodiphenyltrichloroethane (DDTs), Mirex, hexachlorobenzene (HCB), chlordane compounds (CHLs), hexachlorocyclohexane isomers (HCHs), and polybrominated diphenyl ethers (PBDEs). The concentrations ranged from 36 to 7200 ng g-1 lipid weight (lw) and 113-42200 ng g-1 lw for predominant compounds DDTs and PCBs, respectively. Similar profiles of PCB congeners were observed with a predominance of hexachlorinated compounds, representing approximately 50% of the total PCB amount; the highest PCB concentrations were observed from Baixada Santista (SPC) proximate to a highly urbanized and industrial coastal area. Significant differences were observed between the sexes and maturity of dolphins, mainly for PCBs, DDTs, and Mirex. In general, POPs other than HCB in Franciscana dolphins showed downward temporal trends, matching the regulatory periods for restricting and/or banning these compounds. Although POP concentrations are declining, PCB levels remain high in small dolphins, suggesting adverse health effects on Franciscanas. As organic contaminants are one of the numerous threats Franciscanas have been vulnerable to along the Brazilian coast, we recommend monitoring POPs levels every five years to check for declining (or stabilizing) trends.

Photobiomodulation therapy increases functional capacity of patients with chronic kidney failure: randomized controlled trial.

Photobiomodulation (PBM) has been used in different populations as a strategy to attenuate muscle fatigue and improve exercise performance. Recent findings demonstrated that a single session with specific PBM doses during hemodialysis (HD) increased the upper limb muscle strength of chronic kidney failure (CKF) patients. Now, the primary objective of this study was to evaluate the chronic effect of PBM on the functional capacity of this population. Secondarily, we aimed at investigating the effects of PBM on the patients' strength, muscle thickness and echogenicity, perception of pain, fatigue, and quality of life. A randomized controlled trial was conducted in which the intervention group (IG, n = 14) received 24 sessions of PBM (810 nm, 5 diodes × 200 mW, 30 J/application site) on lower limb during HD. The control group (CG, n = 14) did not receive any physical therapy intervention, it only underwent HD sessions. As a result, there was an increase in the functional capacity (assessed through the six-minute walk test) for the IG compared with the CG [50.7 m (CI95% 15.63; 85.72), p = 0.01, large effect size, d = 1.12], as well as an improvement on lower limb muscle strength (assessed through the sit-and-stand test) [- 7.4 s (CI95% - 4.54; - 10.37), p = 0.00, large effect size, d = 1.99]. For other outcomes evaluated, no significant difference between-group was observed. Finally, PBM applied as monotherapy for 8 weeks in the lower limb improves functional capacity and muscle strength of CKF patients.

Home-based inspiratory muscle training in pediatric patients after kidney transplantation: a randomized clinical trial.

BACKGROUND: Chronic kidney disease (CKD) represents the irreversible stages of renal failure and is a growing worldwide public health issue associated with increases in morbidity, mortality, and decreased quality of life. Kidney transplantation is considered one of the best treatment options in this population. However, even after surgery, respiratory muscle strength is below normal values, and inspiratory muscle training (IMT) improves respiratory muscle function, strength, and endurance. This study aimed to evaluate the effects of IMT regarding respiratory muscle strength, functional capacity, and pulmonary function in pediatric kidney transplant recipients with CKD, and secondarily, to assess the biochemical profile of patients after intervention. METHODS: This is a randomized, double-blind, placebo-controlled trial. Patients were randomized into two groups, intervention (IG) and control (CG) and performed IMT home-based training for 6 weeks. In the IG, the load was adjusted to 40% of the maximal inspiratory pressure and in the CG was adjusted to a minimum placebo load (9 cm H2O). RESULTS: Thirty-one patients were randomly allocated to the intervention (n = 16) or control (n = 15) groups. There were no differences at baseline between groups. Increase of 35% in the maximal inspiratory pressure predicted and 26% in the maximal expiratory pressure predicted in the IG were found, compared with 5 and 4% in the CG. There was an increase in hemoglobin and hematocrit values in the IG. CONCLUSIONS: Home-based IMT provides a significant increase in respiratory muscle strength, without changes in functional capacity and pulmonary function. Benefits regarding biochemical markers (hemoglobin and hematocrit) were also observed.

Ankyloglossia Superior Associated With Moebius Syndrome: A Case Report.

Ankyloglossia superior is an exceedingly rare congenital condition that consists of a connection between the tongue and hard palate. This abnormality is considered part of the ankyloglossia superior syndrome when found with other malformations such as limb deformities, gastrointestinal malformation, and cleft palate. Ankyloglossia superior can also be associated with other known syndromes. We have presented the case of a female infant born with multiple malformations, including partial agenesis of the feet and hands, micrognathia, a lack of expression of the facial muscles, convergent strabismus, mouth opening limitation, and tongue-palate adhesion. The patient's presenting diagnosis was ankyloglossia superior associated with Moebius syndrome. Computed tomography revealed the extent of the ankyloglossia superior and the loss of integrity of the palatal shelf. Surgical release of the ankyloglossia superior was performed with the patient under general anesthesia. Multiple management challenges were encountered postoperatively. To the best of our knowledge, ankyloglossia superior presenting in conjunction with Moebius syndrome had not been formally described in a case report.

Influence of synthesis parameters on properties and characteristics of poly (urea-formaldehyde) microcapsules for self-healing applications.

Poly(urea-formaldehyde) (PUF) microcapsules filled with dicyclopentadiene (DCPD) were prepared by in situ polymerisation and the effect of synthesis parameters, such as pH of the solution and agitation rate, on microcapsules size and shell thickness was evaluated. Scanning electron microscopy (SEM) and Fourier transform infra-red spectroscopy (FTIR) were performed. Adjusted pH conditions (pH = 3.5) and agitation rate (1350 RPM) were found using a design of experiments (DOE). SEM results indicated that microcapsule size was directly affected by agitation rate, whereas shell thickness was mostly affected by pH. After obtaining adjusted synthesis conditions, microcapsules presenting mean size of 60 µm and mean shell thickness of 4 µm were embedded in an epoxy matrix for evaluating the self-healing effect. FTIR and SEM analyses in damaged samples suggested that a healing agent was delivered to the crack location.

Implication of Rho-kinase and soluble guanylyl cyclase enzymes in prostate smooth muscle dysfunction in middle-aged rats.

AIMS: Aging is highly associated with benign prostate hyperplasia (BPH). We investigated here the alterations of the contractile and relaxant machinery in prostates of middle-aged rats, focusing on the Rho-kinase, nitric oxide (NO)-soluble guanylyl cyclase (sGC), α1- and ß-adrenoceptor pathways. METHODS: Male Wistar young (3.5-month old) and middle-aged rats (10-month old) were used. Quantitative image analysis of prostates and functional assays evaluating the prostate contractions and relaxations were employed. Measurement of [3 H]-noradrenaline efflux, western blotting for α1 and ß1 sGC subunits, and cyclic nucleotide levels were carried out. RESULTS: Prostates of middle-aged rats showed significant increases in lumen and smooth muscle cells, but no alterations in the relative prostate weight were observed. In vivo, noradrenaline (10-7 -10-4 g/kg) produced greater prostatic contractions in middle-aged compared with control rats. Likewise, the in vitro contractions to phenylephrine (1 nM-100 µM) and α,ß-methylene ATP (1-10 µM) were greater in middle-aged rats. Electrical-field stimulation (EFS, 1-32 Hz) promoted higher [3 H]-noradrenaline efflux and prostate contractions in middle-aged rats. Reduced expressions of α1 and ß1 sGC subunits and diminished NO-mediated prostate relaxations in middle-age were observed. Isoproterenol-induced relaxations and cAMP levels were reduced in prostates of middle-aged rats. The Rho-kinase inhibitor fasudil (50 mg/kg, 2 weeks) normalized the prostate hypercontractility in middle-age rats. CONCLUSIONS: Prostate hypercontractility in middle-aging is associated with increased release of noradrenaline and Rho-kinase pathway, as well as with impairments of NO-sGC and ß-adrenoceptor pathways. Middle-aged rats are suitable to explore the enhanced prostatic tone in the absence of prostate overgrowth. Neurourol. Urodynam. 36:589-596, 2017. © 2016 Wiley Periodicals, Inc.

Validation of the Edinburgh Postnatal Depression Scale (EPDS) for screening of major depressive episode among adults from the general population.

BACKGROUND: Standardized questionnaires designed for the identification of depression are useful for monitoring individual as well as population mental health. The Edinburgh Postnatal Depression Scale (EPDS) has originally been developed to assist primary care health professionals to detect postnatal depression, but several authors recommend its use outside of the postpartum period. In Brazil, the use of the EPDS for screening depression outside the postpartum period and among non-selected populations has not been validated. The present study aimed to assess the validity of the EPDS as a screening instrument for major depressive episode (MDE) among adults from the general population. METHODS: This is a validation study that used a population-based sampling technique to select the participants. The study was conducted in the city of Pelotas, Brazil. Households were randomly selected by two stage conglomerates with probability proportional to size. EPDS was administered to 447 adults (≥20 years). Approximately 17 days later, participants were reinterviewed by psychiatrics and psychologists using a structured diagnostic interview (Mini International Neuropsychiatric Interview, MINI). We calculated the sensitivity and specificity of each cutoff point of EPDS, and values were plotted as a receiver operator characteristic curve. RESULTS: The best cutoff point for screening depression was ≥8, with 80.0% (64.4 - 90.9%) sensitivity and 87.0% (83.3 - 90.1%) specificity. Among women the best cutoff point was ≥8 too with values of sensitivity and specificity of 84.4% (67.2 - 94.7%) and 81.3% (75.5 - 86.1%), respectively. Among men, the best cutoff point was ≥7 (75% sensitivity and 89% specificity). CONCLUSIONS: The EPDS was shown to be suitable for screening MDE among adults in the community.

Influence of the TAS2R38 Gene Single Nucleotide Polymorphisms in Metabolism and Anthropometry in Thyroid Dysfunction.

The gene TAS2R38 single nucleotide polymorphisms (SNPs-P49A, A262V and V296I) can condition bitter tasting by PAV (proline-alanine-valine) and non-bitter-tasting by AVI (alanine-valine-isoleucine) homozygosity. We evaluated this polymorphisms association with thyroid function, metabolism and anthropometry parameters determined by: Endpoint analysis (SNPs); DXA (fat mass-%, total fat mass-kg, lean mass-kg); Standard methods (lipid metabolism parameters, HbA1c-%, glycemia-mg/dL, insulinemia-µIU/mL, HOMA-IR, uricemia-mg/dL, calcemia-mg/dL and BMI-kg/m2); ELISA (leptinemia-ng/mL); Spectrophotometry (Angiotensin Converting Enzyme activity-UI/L). Statistics: SPSS program; OR [IC95%]; p < 0.05. Sample: 114 hypothyroid, 49 hyperthyroid, and 179 controls. An association between A262V-valine-valine and hypothyroidism/hyperthyroidism was verified (OR = 2.841; IC95% [1.726-4.676]), p < 0.001/OR = 8.915; IC95% [4.286-18.543]), p < 0.001). Protector effect from thyroid dysfunction: A262V-alanine-valine (OR = 0.467; IC95% [0.289-0.757], p = 0.002/OR = 0.132; IC95% [0.056-0.309], p < 0.001) and PAV (OR = 0.456; IC95% [0.282-0.737], p = 0.001/OR = 0.101; IC95% [0.041-0.250], p < 0.001). Higher parameter values associated with genotypes were: fat-mass-% (V296I-valine-isoleucine), lean-mass (P49A-proline-proline; PVI), leptin (AVI), HbA1c (A262V-alanine-valine) and lower values in lean-Mass (AVI; PVV), leptin (A262V-alanine-alanine), HbA1c (PVV), uricemia (V296I-valine-isoleucine), glycemia (A262V-alanine-alanine; AAV) and plasma triglycerides (PVV). In conclusion, TAS2R38 influences thyroid function, body composition and metabolism. Bitter taste perception (PAV) and the genotype A262V-alanine-valine can protect from thyroid dysfunction. AVV, PVV and genotype A262V-valine-valine may confer higher predisposition for thyroid dysfunction, particularly PVV for hyperthyroidism.

Obtaining a high titer of polyclonal antibodies from rats to the SARS-CoV-2 nucleocapsid protein and its N- and C-terminal domains for diagnostic test development.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is an enveloped, plus-stranded RNA virus responsible for the Coronavirus Disease 2019 (COVID-19). Patients infected with COVID-19 may be asymptomatic or have symptoms ranging from mild manifestations to severe cases of the disease that could lead to death. The SARS-CoV-2 genome encodes 4 structural proteins, including the Spike protein (S), the Nucleocapsid protein (N), Membrane protein (M) and, the Envelope protein (E). The N protein forms a major component of the ribonucleoprotein complex within the virus particle and play a vital role in its transcription and replication. Nevertheless, the S protein was the most important protein in the development of vaccines against COVID-19. However, the decrease in number of registered immunizations against the disease and the rapid drop in neutralizing antibody titers together with looser preventive measures for virus transmission, favored the rapid appearance of new variants of concerns (VOCs) that primarily show mutations in the S protein. This fact makes the N protein a good candidate for the development of diagnostic tests, due to its stability, amino acid conservation, high immunogenicity, and the smaller likelihood of mutation. With the aim of developing a new diagnostic kit based on the N protein, we evaluated the humoral response in female Wistar rats against this target. Three constructions of the N protein were used to inoculate the animals: the full-length protein (Cfull), the N- (NTD), and the C-terminal (CTD) portion of the protein. The immunizations induced the animal's immune response, with specific polyclonal IgG antibodies against the Cfull protein and its fragments. There were not non-specific bind to the protein used as negative control. Anti-Cfull antibodies demonstrated high efficiency in binding to the NTD protein and the antibodies present in the anti-CTD and anti-NTD sera have recognized the Cfull protein, but they were not able to recognize the NTD and CTD proteins, respectively. Our results indicate an efficient protocol for obtaining high antibody titers against the N recombinant protein of SARS-CoV-2 and its fragments highlighting the Cfull protein, which can be used in the development of new diagnostic kits.

SARS-CoV-2 Rapid Antigen Test Based on a New Anti-Nucleocapsid Protein Monoclonal Antibody: Development and Real-Time Validation.

SARS-CoV-2 diagnostic tests have become an important tool for pandemic control. Among the alternatives for COVID-19 diagnosis, antigen rapid diagnostic tests (Ag-RDT) are very convenient and widely used. However, as SARS-CoV-2 variants may continuously emerge, the replacement of tests and reagents may be required to maintain the sensitivity of Ag-RDTs. Here, we describe the development and validation of an Ag-RDT during an outbreak of the Omicron variant, including the characterization of a new monoclonal antibody (anti-DTC-N 1B3 mAb) that recognizes the Nucleocapsid protein (N). The anti-DTC-N 1B3 mAb recognized the sequence TFPPTEPKKDKKK located at the C-terminus of the N protein of main SARS-CoV-2 variants of concern. Accordingly, the Ag-RDT prototypes using the anti-DTC-N 1B3 mAB detected all the SARS-CoV-2 variants-Wuhan, Alpha, Gamma, Delta, P2 and Omicron. The performance of the best prototype (sensitivity of 95.2% for samples with Ct ≤ 25; specificity of 98.3% and overall accuracy of 85.0%) met the WHO recommendations. Moreover, results from a patients' follow-up study indicated that, if performed within the first three days after onset of symptoms, the Ag-RDT displayed 100% sensitivity. Thus, the new mAb and the Ag-RDT developed herein may constitute alternative tools for COVID-19 point-of-care diagnosis and epidemiological surveillance.

Effects of the combination of low-level laser irradiation and recombinant human bone morphogenetic protein-2 in bone repair.

Low-level laser irradiation (LLLI) and recombinant human bone morphogenetic protein type 2 (rhBMP-2) have been used to stimulate bone formation. LLLI stimulates proliferation of osteoblast precursor cells and cell differentiation and rhBMP-2 recruits osteoprogenitor cells to the bone healing area. This in vivo study evaluated the effects of LLLI and rhBMP-2 on the bone healing process in rats. Critical bone defects were created in the parietal bone in 42 animals, and the animals were divided into six treatment groups: (1) laser, (2) 7 µg of rhBMP-2, (3) laser and 7 µg of rhBMP-2, (4) 7 µg of rhBMP-2/monoolein gel, (5) laser and 7 µg rhBMP-2/monoolein gel, and (6) critical bone defect controls. A gallium-aluminum-arsenide diode laser was used (wavelength 780 nm, output power 60 mW, beam area 0.04 cm(2), irradiation time 80 s, energy density 120 J/cm(2), irradiance 1.5 W/cm(2)). After 15 days, the calvarial tissues were removed for histomorphometric analysis. Group 3 defects showed higher amounts of newly formed bone (37.89%) than the defects of all the other groups (P < 0.05). The amounts of new bone in defects of groups 1 and 4 were not significantly different from each other (24.00% and 24.75%, respectively), but were significantly different from the amounts in the other groups (P < 0.05). The amounts of new bone in the defects of groups 2 and 5 were not significantly different from each other (31.42% and 31.96%, respectively), but were significantly different from the amounts in the other groups (P < 0.05). Group 6 defects had 14.10% new bone formation, and this was significantly different from the amounts in the other groups (P < 0.05). It can be concluded that LLLI administered during surgery effectively accelerated healing of critical bone defects filled with pure rhBMP-2, achieving a better result than LLLI alone or the use of rhBMP-2 alone.

Ti3C2 MXene Membranes for Gas Separation: Influence of Heat Treatment Conditions on D-Spacing and Surface Functionalization.

Two-dimensional (2D) MXene materials have recently been the focus of membrane research due to their unique properties, such as their single-atomic-layer thickness, flexibility, molecular filtration abilities and microstructural similarities with graphene, which is currently the most efficient precursor material for gas separation applications. In addition, the potential to process nanoscale channels has motivated investigations of parameters which can improve membrane permeability and selectivity. Interlayer spacing and defects, which are still challenging to control, are among the most crucial parameters for membrane performance. Herein, the effect of heat treatment on the d-spacing of MXene nanosheets and the surface functionalization of nanolayers was shown regarding its impact on the gas diffusion mechanism. The distance of the layers was reduced by a factor of over 10 from 0.345 nm to 0.024 nm, the defects were reduced, and the surface functionalization was maintained upon treatment of the Ti3C2 membrane at 500 °C under an Ar/H2 atmosphere as compared to 80 °C under vacuum. This led to a change from Knudsen diffusion to molecular sieving, as demonstrated by single-gas permeation tests at room temperature. Overall, this work shows a simple and promising way to improve H2/CO2 selectivity via temperature treatment under a controlled atmosphere.

Vascular endothelial growth factor (VEGF) and interleukin-1 receptor antagonist (IL-1Ra) as promising biomarkers for distinguishing active from latent tuberculosis in children and adolescents.

Since distinguishing pulmonary (PTB) from latent tuberculosis (LTBI) in pediatric patients remains a challenge, we aimed to investigate the efficacy of immune mediators in diagnosing PTB and LTBI in this population. In this cross-sectional study performed with children and adolescents, serum levels of 20 biomarkers were assessed and data were analyzed according to age groups. We included 65 participants (PTB, n = 28 and LTBI, n = 37). Overall, levels of TNF-α, IL-1Ra, IL-6, IL-17A, VEGF, MMP-1, and procalcitonin were significantly higher (P < 0.05) in adolescents and children <10 years-old with PTB. Also, principal component analysis (PCA) showed that immune mediators were able to distinguish PTB from LTBI. VEGF and IL-1Ra presented the highest area under the curve (AUC) values, both separately (AUC 0.890 and 0.785) and combined (AUC 0.99). Taken together, we showed that VEGF and IL-1Ra are promising biomarkers to distinguish PTB from LTBI in pediatric patients, especially in children <5 years-old.

SARS-CoV-2 Nucleocapsid Protein is Associated With Lower Testosterone Levels: An Experimental Study.

The ongoing COVID-19 pandemic represents an extra burden in the majority of public and private health systems worldwide beyond the most pessimistic expectations, driving an urgent rush to develop effective vaccines and effective medical treatments against the SARS-CoV-2 pandemic. The Nucleocapsid structural viral protein is remarkably immunogenic and hugely expressed during infection. High IgG antibodies against Nucleocapsid protein (N protein) levels were detected in the serum of COVID-19 patients, confirming its pivotal antigen role for a T lymphocyte response in a vaccine microenvironment. Currently, adverse events associated with immunizations have raised some degree of concern, irrespective of its huge benefits in dealing with disease severity and decreasing mortality and morbidity. This hitherto study evaluates histological changes in rats' testes, epididymis, prostate, and seminal vesicles and analyzes hormone levels after solely N protein inoculation. Therefore, we exposed a group of Lewis rats to weekly injections of the recombinant N protein for 28 days, while a control group was inoculated with a buffer solution. The N group revealed a more significant number of spermatozoa. Spermatozoa in the seminiferous tubules were counted in twenty 400 × microscopy fields (mean of 9.2 vs. 4.6 in the control group; p < 0,01), but significantly lower testosterone levels (mean of 125.70 ng/dl vs. 309,00 ng/dl in the control group; p < 0,05) were found. No other histological and biochemical changes were displayed. Conclusively, these data suggest testicular hormonal imbalance mediated by the SARS-CoV-2 N protein that could be linked to reported post-COVID-19 syndrome hypogonadism. More relevant research might be performed to confirm this viral antigen's deleterious mechanism in the human testicular microenvironment, particular in Leydig cell function.

Toxicity of spike fragments SARS-CoV-2 S protein for zebrafish: A tool to study its hazardous for human health?

Despite the significant increase in the generation of SARS-CoV-2 contaminated domestic and hospital wastewater, little is known about the ecotoxicological effects of the virus or its structural components in freshwater vertebrates. In this context, this study evaluated the deleterious effects caused by SARS-CoV-2 Spike protein on the health of Danio rerio, zebrafish. We demonstrated, for the first time, that zebrafish injected with fragment 16 to 165 (rSpike), which corresponds to the N-terminal portion of the protein, presented mortalities and adverse effects on liver, kidney, ovary and brain tissues. The conserved genetic homology between zebrafish and humans might be one of the reasons for the intense toxic effects followed inflammatory reaction from the immune system of zebrafish to rSpike which provoked damage to organs in a similar pattern as happen in severe cases of COVID-19 in humans, and, resulted in 78,6% of survival rate in female adults during the first seven days. The application of spike protein in zebrafish was highly toxic that is suitable for future studies to gather valuable information about ecotoxicological impacts, as well as vaccine responses and therapeutic approaches in human medicine. Therefore, besides representing an important tool to assess the harmful effects of SARS-CoV-2 in the aquatic environment, we present the zebrafish as an animal model for translational COVID-19 research.

A WNK4 gene variant relates to osteoporosis and not to hypertension in the Portuguese population.

Germline mutations in the WNK4 gene originate Gordon syndrome or pseudohypoaldosteronism type II, a familial form of hypertension with hyperkalemia and hypercalciuria. In order to elucidate the contribution of WNK4 genetic variants to hypertension and/or osteoporosis, we analyzed 271 control individuals and a cohort of 448 hypertensive and 372 osteoporosis patients from the Portuguese population. Ten genetic variants were detected in 4.3% of the population under study, none of which revealed any significant association to the hypertension phenotype. In contrast, a rare missense alteration within exon 17 in a highly conserved arginine residue showed a possible tendency for association to the osteoporosis group. Our data suggest that WNK4 polymorphism rs56116165 is a rare allelic variant in a candidate gene with a biological function in renal calcium homeostasis that may contribute to a genetic predisposition to osteoporosis.

Development and psychometric validation of Internet Gaming Disorder Scale-Short-Form (IGDS9-SF) in a Brazilian sample.

OBJECTIVES: The aim of this study was to develop and examine the psychometric properties of the IGDS9-SF in a sample of Brazilian gamers and to find the best cut-off point for this instrument using a normative and clinically diagnosed sample of gamers. METHODS: A total of 610 participants were recruited to the present study. Construct validity was assessed through Exploratory and Confirmatory Factor Analysis (EFA, CFA). Criterion-related validity was established through the associations with Game Addiction Scale (GAS) and weekly gameplay. Reliability analysis was performed using the Cronbach's alpha (α) as the indicator of internal consistency. A cut-off point was estimated using the Receiver Operating Characteristics Curve (ROC curve) where the results of a clinical assessment was used as the gold standard. RESULTS: EFA and CFA findings confirmed the single-factor structure of the IGDS9-SF. Positive correlations indicated adequate criterion-related validity, and the scale was shown to be reliable (α=0.82). Finally, the optimal cut-off point for risky gaming was found to be >16 points and for diagnosis to be >21 points. CONCLUSIONS: This study provides validity and reliability evidence for the use of the Brazilian version of the IGDS9-SF in the assessment of Internet Gaming Disorder, further supporting its usefulness as a robust psychometric tool that can be employed in clinical and research settings in Brazil.

An association between successful engraftment of osteosarcoma patient-derived xenografts and clinicopathological findings.

Although osteosarcoma is a rare disease, with a global incidence rate estimated at 5.0/million/year, it is the most frequent primary bone sarcoma in children and adolescents. In translational research, the patient-derived xenograft (PDX) model is considered an authentic in vivo model for several types of cancer, as tumorgrafts faithfully retain the biological characteristics of the primary tumors. Our goal was to investigate the association between PDX formation and clinical findings of osteosarcoma patients and the ability of the model to preserve in immunocompromized mice the characteristics of the parental tumor. A fresh sample of the patient tumor obtained from a representative biopsy or from surgical resection was implanted into nude mice. When tumor outgrowths reached ~1,500mm³, fresh PDX fragments were re-transplanted into new hosts. Engraftment in mice was obtained after a latency period of 19-225 days (median 92 days) in 40.54% of the implanted samples. We confirmed the histopathological fidelity between the patient tumor and their respective established PDXs, including the expression of biomarkers. PDX take rate was higher in surgical resection samples, in post-chemotherapy surgical samples and in samples from patients with metastatic disease at presentation. In conclusion, we have shown that the osteosarcoma PDX model reliably recapitulates the morphological aspects of the human disease after serial passage in mice. The observation that more aggressive forms of osteosarcoma, including those with metastatic disease at presentation, have a higher efficiency to generate PDXs provides a promising scenario to address several unanswered issues in clinical oncology.

Serological biomarkers for monitoring response to treatment of pulmonary and extrapulmonary tuberculosis in children and adolescents.

Key measures to halt the spread of tuberculosis (TB) include early diagnosis, effective treatment, and monitoring disease management. We sought to evaluate the use of serum immunoglobulin levels against antigens present in cell envelope of Mycobacterium tuberculosis to monitor TB treatment response in children and adolescents with pulmonary (PTB) or extrapulmonary TB (EPTB). Blood samples were collected prior to and one, two, and six months following treatment initiation. Serum immunoglobulin levels against cardiolipin, sulfatide, mycolic acid and Mce1A protein were measured by ELISA. Serum from 53 TB patients and 12 healthy participants were analyzed. After six months of successful treatment, there was a significant decrease (p < 0.0001) in IgM levels against cardiolipin, sulfatide, mycolic acid and Mce1A protein and IgG levels against Mce1A protein when compared to baseline immunoglobulin levels. There was no significant variation in antibody levels during follow-up between participants with PTB and EPTB, confirmed and unconfirmed TB diagnosis, and HIV infection status. Antibody levels in control participants without TB did not decrease during follow-up. These results suggest that immunoglobulin responses to mycobacterial cell wall products may be a useful tool to monitor treatment response in children and adolescents with PTB or EPTB.