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Persiste la necesidad de dirigir investigaciones científicas que permitan ampliar la comprensión de las características psicosociales y patológicas de los estudiantes adolescentes con discapacidad motora. El objetivo del presente trabajo es determinar la prevalencia de los factores sexo, edad, gravedad y causa de la discapacidad física con relación a las características psicosociales de los adolescentes con deficiencia motora de la provincia de Manabí en Ecuador. La muestra está integrada por 100 estudiantes con edades entre 11 a 19 años, de sexo femenino y masculino; todos diagnosticados con diversos grados de discapacidad motora. Durante el periodo 2018-2020 se administraron instrumentos de medición que permitieron determinar que las participantes de sexo femenino reportan conductas de autocontrol con mayor frecuencia que los participantes de sexo masculino, pero ellas reportan mayor ansiedad social que los de sexo masculino. Ellas tienen mayores percepciones de soporte emocional, amor y afecto; mientras que ellos tienen mayor participación en victimización, agresión y victimización agresiva. El grupo entre 16 y 19 años mostró mayor perseverancia, y el grupo entre 11 y 13 años presentó mayor nivel de victimización. Se concluye que los participantes que tienen discapacidad motora grave reportaron mayor autoestima y los que tienen discapacidad leve presentaron más somatización y ansiedad ante los hechos cotidianos suscitados en el plantel.

OBJECTIVE: The aim was to evaluate immunoexpression of matrix metalloproteinases (MMPs) 1, 2, 7, 9, and 26 in calcifying cystic odontogenic tumor (CCOT). STUDY DESIGN: Ten cases of CCOT were assessed by immunohistochemical expression of MMPs 1, 2, 7, 9, and 26 in the parenchyma and stroma. Metalloproteinase immunoexpressions and their distribution pattern were semiquantitatively scored. RESULTS: MMPs were expressed in the parenchyma and stroma in all cases of CCOT. Regarding the percentage of immunostained parenchymal cells, MMPs 1, 7, and 9 showed score 2 in 100% of cases. For MMP-2, there was a predominance of score 0 (90%), whereas for MMP-26 immunostaining was varied. CONCLUSIONS: The staining of these metalloproteinases, with the exception of MMP-2, suggests their contribution to tumor growth and expansion. The presence of these metalloproteinases in stromal cells reveals the active participation of these cells in the degradation of the extracellular matrix, contributing to the growth of the tumor studied. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The aim was to analyze the expression of E-cadherin and beta-catenin in ameloblastomas and tooth germs to determine their roles in cell differentiation processes and invasiveness compared with odontogenesis. STUDY DESIGN: Twenty-one ameloblastoma cases (16 solid and 5 unicystic tumors) and 5 tooth germs were submitted to the immunohistochemical detection of E-cadherin and beta-catenin. Immunoreactivity was evaluated using descriptive and semiquantitative analysis, investigating the location and intensity of staining. The Fisher exact test was performed, and P values of <.05 were considered to indicate statistical significance. RESULTS: There was no statistically significant difference in the expression of E-cadherin and beta-catenin between solid and unicystic ameloblastomas (P = .59; P = .63; respectively). The same was found when comparing solid and unicystic ameloblastomas with the tooth germs for both E-cadherin (P = .53; P = .44; respectively) and beta-catenin (P = .12; P = .16; respectively). Nuclear staining of beta-catenin was observed in only 4 cases (3 solid and 1 unicystic tumor). CONCLUSION: The results showed no differences in the expression of E-cadherin or beta-catenin between tooth germs and solid and unicystic ameloblastomas. The expression of these molecules seems mainly to be related to the process of cell differentiation. [ABSTRACT FROM AUTHOR]

Alzheimer’s disease (AD) constitutes a neurodegenerative pathology that presents mobility disorders as one of its earliest symptoms. Current smartphones integrate accelerometers that can be used to collect mobility data of Alzheimer’s patients. This paper describes a method that processes these accelerometer data and a convolutional neural network (CNN) that classifies the stage of the disease according to the mobility patterns of the patient. The method is applied in a case study with 35 Alzheimer’s patients, in which a classification success rate of 91% was obtained.

Controlled nuclear fusion aims to obtain energy by particles collision confined inside a nuclear reactor (Tokamak). These ionized particles, heavier isotopes of hydrogen, are the main elements inside of plasma that is kept at high temperatures (millions of Celsius degrees). Due to high temperatures and magnetic confinement, plasma is exposed to several sources of instabilities which require a set of procedures by the control and data acquisition systems throughout fusion experiments processes. Control and data acquisition systems often used in nuclear fusion experiments are based on the Advanced Telecommunication Computer Architecture (AdvancedTCA®) standard introduced by the Peripheral Component Interconnect Industrial Manufacturers Group (PICMG®), to meet the demands of telecommunications that require large amount of data (TB) transportation at high transfer rates (Gb/s), to ensure high availability including features such as reliability, serviceability and redundancy. For efficient plasma control, systems are required to collect large amounts of data, process it, store for later analysis, make critical decisions in real time and provide status reports either from the experience itself or the electronic instrumentation involved. Moreover, systems should also ensure the correct handling of detected anomalies and identified faults, notify the system operator of occurred events, decisions taken to acknowledge and implemented changes. Therefore, for everything to work in compliance with specifications it is required that the instrumentation includes hardware management and monitoring mechanisms for both hardware and software. These mechanisms should check the system status by reading sensors, manage events, update inventory databases with hardware system components in use and maintenance, store collected information, update firmware and installed software modules, configure and handle alarms to detect possible system failures and prevent emergency scenarios occurrences. The goal is to ensure high availability of the system and provide safety operation, experiment security and data validation for the fusion experiment. This work aims to contribute to the joint effort of the IPFN control and data acquisition group to develop a hardware management and monitoring application for control and data acquisition instrumentation especially designed for large scale tokamaks like ITER.

The achievements coming from genome analysis depend greatly on the quality of computational and processing methods. Tools for functional mRNA profiling and for gene information integration have become essential to this task. We have developed GeneBrowser as a novel approach that combines the advantages of mRNA profiling tools, at genome-scale experiments, with the features provided by data integration systems. For a given set of genes, GeneBrowser integrates bibliography information with functional annotations, using Gene Ontology, Entrez Gene, KEGG Orthology and KEGG Pathways. The result is a comprehensive and easy to use web application that helps researchers to extract knowledge from large data sets and to speed up the discovery process.

Este é um estudo, de caráter analítico-descritivo, que teve como objetivo descrever as alterações morfológicas da traquéia de pacientes intubados com cânulas de alto volume residual e baixa pressão no "cuff", mantidos em ventilação mecânica com pressão intra -"cuff" menor que a capilar da traquéia (20 a 30 mmHg), em função do tempo de intubação. A população constou de 23 pacientes adultos, internados em uma UTI, intubados por períodos entre 27 a 317 horas, e que foram a óbito, necessitando de necropsia para identificação da causa mortis. As alterações encontradas limitaram-se apenas à mucosa da traquéia, atingindo somente o epitélio de revestimento e a lâmina própria, e o tempo de intubação foi um fator determinante do agravamento das lesões na parede traqueal.

Este trabalho objetivou conhecer o grau de colonização pelo Staphylococcus aureus e a evolução do estado de portador são em alunos de um curso de Auxiliar de Enfermagem, durante a formação profissional. Participaram 42 alunos, dos quais foram colhidas amostras da cavidade nasal e mãos (direita e esquerda) em seis diferentes momentos da formação. Do total de alunos, 19 (45,2%) comportaram-se como portadores ocasionais, 12 (28,6%) como intermitentes, 6 (14,3%) como persistentes e 5 (11,9%) como não portadores, demonstrando que a colonização não aumentou com o decorrer do curso. Dos alunos, 24 (57,1%) referiram não terem desenvolvido atividades relacionadas à enfermagem antes e/ou durante o curso e 18 (42,9%) referiram exercê-las como atendentes.

Although AIDS patients in other countries are frequently diagnosed as having atypical mycobacterial infection, in Southern Brazil there is a clinical impression that Mycobacterium tuberculosis is the rule rather than the exception. We made a retrospective review of cultures for mycobacteria at our hospital in order to determine the frequency of atypical mycobacteria and Mycobacterium tuberculosis in hospitalised patients in Porto Alegre, Brazil. Mycobacterium tuberculosis was the most frequent isolate (79.9%), regardless of HIV serostatus. Only 1.5% of the cultures yielded atypical mycobacteria, all of which in AIDS patients. Mycobacterium tuberculosis was diagnosed in most of the HIV-infected patients (81.2%). We conclude that Mycobacterium tuberculosis is frequent in both HIV infected and non-HIV infected patients in this part of the country.

Abstract Background The presence of microalbuminuria can be associated with overt nephropathy and cardiovascular disease in patients with type 1 diabetes (T1D). We aimed to determine the incidence and evaluate the baseline predictors for the development of microalbuminuria in patients with T1D. Methods This study is a longitudinal cohort study of 122 normoalbuminuric patients with T1D who were receiving routine clinical care at baseline. A detailed medical history was taken, and a physical examination was performed at baseline. All of the patients were regularly examined for diabetes-associated complications. An analysis of predictors was performed using the Cox regression. Results Over 6.81 (3.59-9.75) years of follow-up, 50 (41%) of the patients developed microalbuminuria. The incidence density was 6.79/100 people per year (95% CI 5.04-8.95), and the microalbuminuria developed after 5.9 (2.44-7.76) and 11 (5-15) years of follow-up and diabetes duration, respectively. After an individual Cox regression, the baseline variables associated with the development of microalbuminuria were age, age at diagnosis, duration of diabetes, systolic and diastolic blood pressure, fasting glycemia, body mass index (BMI), total cholesterol and triglycerides levels, cholesterol/HDL ratio and a family history of type 2 diabetes.After a multivariate Cox regression, the only independent factors associated with the development of microalbuminuria were BMI [HR 1.12 (1.03-1.21)] and cholesterol/HDL ratio [HR 1.32 (1.05-1.67)]. Conclusions A higher BMI and cholesterol/HDL ratio increased the risk of developing microalbuminuria in young patients with T1D after a short follow-up. Both risk factors are modifiable and should be identified early and followed closely.

Abstract Background MicroRNAs (miRNAs) are a new class of small RNAs of approximately 22 nucleotides in length that control eukaryotic gene expression by fine tuning mRNA translation. They regulate a wide variety of biological processes, namely developmental timing, cell differentiation, cell proliferation, immune response and infection. For this reason, their identification is essential to understand eukaryotic biology. Their small size, low abundance and high instability complicated early identification, however cloning/Sanger sequencing and new generation genome sequencing approaches overcame most technical hurdles and are being used for rapid miRNA identification in many eukaryotes. Results We have applied 454 DNA pyrosequencing technology to miRNA discovery in zebrafish (Danio rerio). For this, a series of cDNA libraries were prepared from miRNAs isolated at different embryonic time points and from fully developed organs. Each cDNA library was tagged with specific sequences and was sequenced using the Roche FLX genome sequencer. This approach retrieved 90% of the 192 miRNAs previously identified by cloning/Sanger sequencing and bioinformatics. Twenty five novel miRNAs were predicted, 107 miRNA star sequences and also 41 candidate miRNA targets were identified. A miRNA expression profile built on the basis of pyrosequencing read numbers showed high expression of most miRNAs throughout zebrafish development and identified tissue specific miRNAs. Conclusion This study increases the number of zebrafish miRNAs from 192 to 217 and demonstrates that a single DNA mini-chip pyrosequencing run is effective in miRNA identification in zebrafish. This methodology also produced sufficient information to elucidate miRNA expression patterns during development and in differentiated organs. Moreover, some zebrafish miRNA star sequences were more abundant than their corresponding miRNAs, suggesting a functional role for the former in gene expression control in this vertebrate model organism.

The objective was to evaluate the biosolids as an alternative source of nutrients in the production of chrysanthemums by adding increasing doses to the cultivation substrate. The experimental design was in blocks with 6 treatments and 5 replications. The treatments consisted of the mixture (commercial substrate + biosolid) at the concentrations: 20%, 40%, 60% and 80% of biosolid + two controls (100% of biosolid and 100% of substrate). The experiment was conducted in a greenhouse for 90 days. Physiological parameters, number of flower buds, dry biomass and nutrient accumulation were evaluated. Physiological parameters were evaluated using the Infrared Gas Analyzer. The number of flower buds was evaluated by counting. Biomass was determined after drying the structures and then calculated the accumulation of nutrients. A total of 90 plants were evaluated. Concentrations of up to 40% of biosolid promoted a greater number of flower buds, dry biomass and nutrient accumulation. Concentrations above 60% lower number of buds, biomass increment and nutrient accumulation. It is concluded that the biosolid has potential as an alternative source of nutrients in the cultivation of chrysanthemums, indicating concentrations of up to 40% and the nutrient content of each batch generated must be verified., (© 2024. The Author(s).)

The safe management of sewage waste is a current concern due to population growth and waste production. Biosolids, derived from sewage sludge treatment, are globally used as organic fertilizers, aligning with Sustainable Development Goal 6 for resource recycling. However, biosafety concerns arise due to the presence of metals and microplastics in biosolids, potentially impacting soil and water. This study investigated biosolids' use for in vitro cultivation of Bowdichia virgilioides Kunth. Results indicate that while biosolids can replace traditional nutritional media, balancing their concentration is crucial for optimizing plant growth. The WPM (Wood Plat Medium) remains essential for in vitro cultivation, but substituting it with biosolids at concentrations of up to 2 g L - 1 is feasible, providing similar plant development compared to the WPM medium. However, when combined, there is a complex and challenging interaction between biosolids and the culture medium., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Oxidative stress (OS) and endoplasmic reticulum stress (ERS) are at the genesis of placental disorders observed in preeclampsia, intrauterine growth restriction, and maternal hypothyroidism. In this regard, cationic manganese porphyrins (MnPs) comprise potent redox-active therapeutics of high antioxidant and anti-inflammatory potential, which have not been evaluated in metabolic gestational diseases yet. This study evaluated the therapeutic potential of two MnPs, [MnTE-2-PyP] 5+ (MnP I) and [MnT(5-Br-3-E-Py)P]5+ (MnP II), in the fetal-placental dysfunction of hypothyroid rats. Hypothyroidism was induced by administration of 6-Propyl-2-thiouracil (PTU) and treatment with MnPs I and II 0.1 mg/kg/day started on the 8th day of gestation (DG). The fetal and placental development, and protein and/or mRNA expression of antioxidant mediators (SOD1, CAT, GPx1), hypoxia (HIF1α), oxidative damage (8-OHdG, MDA), ERS (GRP78 and CHOP), immunological (TNFα, IL-6, IL-10, IL-1β, IL-18, NLRP3, Caspase1, Gasdermin D) and angiogenic (VEGF) were evaluated in the placenta and decidua on the 18th DG using immunohistochemistry and qPCR. ROS and peroxynitrite (PRX) were quantified by fluorometric assay, while enzyme activities of SOD, GST, and catalase were evaluated by colorimetric assay. MnPs I and II increased fetal body mass in hypothyroid rats, and MnP I increased fetal organ mass. MnPs restored the junctional zone morphology in hypothyroid rats and increased placental vascularization. MnPs blocked the increase of OS and ERS mediators caused by hypothyroidism, showing similar levels of expression of HIFα, 8-OHdG, MDA, Gpx1, GRP78, and Chop to the control. Moreover, MnPs I and/or II increased the protein expression of SOD1, Cat, and GPx1 and restored the expression of IL10, Nlrp3, and Caspase1 in the decidua and/or placenta. However, MnPs did not restore the low placental enzyme activity of SOD, CAT, and GST caused by hypothyroidism, while increased the decidual and placental protein expression of TNFα. The results show that treatment with MnPs improves the fetal-placental development and the placental inflammatory state of hypothyroid rats and protects against oxidative stress and reticular stress caused by hypothyroidism at the maternal-fetal interface., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Syphilis coinfection among pregnant people living with HIV (PLH) may worsen pregnancy outcomes. We evaluated the impact of syphilis coinfection on pregnancies in south Brazil., Methods: Data were extracted from hospital records between January 1, 2008, and December 31, 2018. Preterm birth (PTB), low birth weight (LBW <2500 g), and a composite adverse infant outcome (AIO: HIV vertical transmission, loss to follow-up before HIV diagnosis, stillbirth, congenital syphilis) were evaluated among pregnancies without HIV and syphilis (PWOH + S), PLH monoinfection, syphilis monoinfection (PLS), and PLH with syphilis (PLH + S)., Results: Among 48,685 deliveries where patients were tested for HIV and syphilis, 1353 (2.8%) occurred in PLH; of these, 181 (13.4%) were HIV/syphilis coinfected (PLH + S). Among PLH, 2.4% of infants acquired HIV and 13.1% were lost to follow-up before HIV diagnosis. Among all PLS, 70.5% of infants acquired congenital syphilis. Across the cohort, 1.2% stillbirths/neonatal deaths occurred. Thirty-seven percent of PLH + S did not initiate antiretroviral therapy versus 15.4% of PLH monoinfection ( P < 0.001). Less than half (37.6%) of PLH + S had VDRL titers ≥1:16 compared with 21.7% of PLS only ( P < 0.001). Among PLH, syphilis coinfection and unknown/high VDRL titers (≥1:16) increased AIO risk more (adjusted relative risk [aRR], 3.96; 95% confidence interval [CI], 3.33-4.70) compared with low VDRL titers (≤1:8; aRR, 3.51; 95% CI, 2.90-4.25). Unsuppressed viremia (≥50 copies/mL) was associated with risk of PTB (aRR, 1.43; 95% CI, 1.07-1.92) and AIO (aRR, 1.38; 95% CI, 1.11-1.70) but not LBW. Lack of prenatal care was significant in predicting PTB and LBW in all PLH and PLS monoinfection., Conclusions: Syphilis coinfection worsens AIOs in all women and compounds negative effects of HIV infection during pregnancy. Effective syphilis treatment and HIV viral load suppression are paramount for optimal obstetric care., Competing Interests: Conflict of Interest and Sources of Funding: The authors have no competing interests or conflicts to declare., (Copyright © 2024 American Sexually Transmitted Diseases Association. All rights reserved.)

Purpose: Central and peripheral chemoreceptors are hypersensitized in patients with heart failure with reduced ejection fraction. Whether this autonomic alteration occurs in patients with heart failure with preserved ejection fraction (HFpEF) remains little known. We test the hypothesis that the central and peripheral chemoreflex control of muscle sympathetic nerve activity (MSNA) is altered in HFpEF., Methods: Patients aged 55-80 years with symptoms of heart failure, body mass index ≤ 35 kg/m 2 , left ventricular ejection fraction > 50%, left atrial volume index > 34 mL/m 2 , left ventricular early diastolic filling velocity and early diastolic tissue velocity of mitral annulus ratio (E/e' index) ≥ 13, and BNP levels > 35 pg/mL were included in the study (HFpEF, n = 9). Patients without heart failure with preserved ejection fraction (non-HFpEF, n = 9), aged-paired, were also included in the study. Peripheral chemoreceptors stimulation (10% O 2 and 90% N 2 , with CO 2 titrated) and central chemoreceptors stimulation (7% CO 2 and 93% O 2 ) were conducted for 3 min. MSNA was evaluated by microneurography technique, and forearm blood flow (FBF) by venous occlusion plethysmography., Results: During hypoxia, MSNA responses were greater (p < 0.001) and FBF responses were lower in patients with HFpEF (p = 0.006). Likewise, MSNA responses during hypercapnia were higher (p < 0.001) and forearm vascular conductance (FVC) levels were lower (p = 0.030) in patients with HFpEF., Conclusions: Peripheral and central chemoreflex controls of MSNA are hypersensitized in patients with HFpEF, which seems to contribute to the increase in MSNA in these patients. In addition, peripheral and central chemoreceptors stimulation in patients with HFpEF causes muscle vasoconstriction., (© 2024. Springer-Verlag GmbH Germany.)

It is unclear whether muscle blood flow (MBF) is altered in long-term Hodgkin lymphoma (HL) survivors. We tested the hypothesis that 1 ) MBF response during mental stress (MS) is impaired in long-term HL survivors and 2 ) aerobic exercise training combined with local strength exercise (ET) restores MBF responses during MS in these survivors. Eighteen 5-year HL survivors and 10 aged-paired healthy subjects (HC) were studied. Twenty HL survivors were randomly divided into two groups: exercise-trained (HLT, n = 10) and untrained (HLUT, n = 10). Maximal aerobic capacity was evaluated by a cardiopulmonary exercise test and forearm blood flow (FBF) by venous occlusion plethysmography. MS was elicited by Stroop color and word test. ET was conducted for 4 mo, 3/wk for 60 min each session. The aerobic exercise intensity corresponded to anaerobic threshold up to 10% below the respiratory compensation point. The strength exercises consisted of two to three sets of chest press, pulley and squat exercises, 12-15 repetitions each exercise at 30-50% of the maximal voluntary contraction. Baseline was similar in HL survivors and HC, except peak oxygen consumption (peak V̇o 2 , P = 0.013) and FBF ( P = 0.006) that were lower in the HL survivors. FBF responses during MS were lower in HL survivors ( P < 0.001). ET increased peak V̇o 2 (11.59 ± 3.07%, P = 0.002) and FBF at rest (33.74 ± 5.13%, P < 0.001) and during MS (24 ± 5.31%, P = 0.001). Further analysis showed correlation between the changes in peak V̇o 2 and the changes in FBF during MS (r = 0.711, P = 0.001). In conclusion, long-term HL survivors have impaired MBF responses during MS. ET restores MBF responses during MS. NEW & NOTEWORTHY Long-term Hodgkin lymphoma (HL) survivors have impaired muscle blood flow responses during mental stress and decreased maximal aerobic capacity. Supervised aerobic exercise training combined with local strength exercises restores muscle blood flow responses during mental stress and maximal aerobic capacity in these survivors. These findings provide evidence of safety and effectiveness of exercise training in HL survivors. Moreover, they highlight the importance of exercise training in the treatment of this set of patients.

In Brazil, acanthocephalans parasitise anurans in several biomes. In the present study, we performed an analysis of acanthocephalan infections across 175 anuran individuals from the Cerrado biome, belonging to ten species: Boana raniceps, Pithecopus hypochondrialis, Scinax fuscomarginatus, Scinax x-signatus , Leptodactylus pustulatus, Leptodactylus macrosternum, Leptodactylus vastus, Physalaemus cuvieri, Adenomera hylaedactyla , and Elachistocleis piauiensis. We also verified the specificity of the parasites using the S TD * index. Additionally, we conducted a survey of acanthocephalan infection in anurans in South America. The studied assemblage in the Brazilian Cerrado presented 57 parasitised hosts of 175 specimens (overall prevalence: 32.6%). In total, 437 acanthocephalans cystacanths were recorded, among which 286 presented the same morphotype but could not be identified, 148 belonged to the genus Centrorhynchus , and three belonged to Oncicola . Unidentified acanthocephalans had a higher prevalence in L. vastus (53.85%) and the highest intensity was in L. pustulatus (17±16). The highest prevalence of Centrorhynchus sp. was in the species S. fuscomarginatus (28.57%), while the highest intensity was observed in L. vastus (111). The taxon Oncicola sp. it had a prevalence of 3.23% and an intensity of 3 only in S. x-signatus . The highest specificity was recorded for Oncicola sp. ( S TD *= 1), whereas the lowest was found in Centrorhynchus sp. ( S TD *= 2.21). Finally, according to the survey for South America, we found ten records of acanthocephalan taxa parasitizing 58 species of anurans distributed in seven countries (Brazil with the most records).

Hypothyroidism compromises the testicular redox status and is associated with reduced sperm quality and infertility in men. In this regard, studies have demonstrated the antioxidant potential of kisspeptin in reproductive and metabolic diseases. In this study, we evaluate the effects of kisspeptin-10 (Kp10) on the testicular redox, as well as mediators of the unfolded protein response (UPR) in adult rats with hypothyroidism. Adult male Wistar rats were randomly separated into the Control ( n = 15), Hypo ( n = 13) and Hypo + Kp10 ( n = 14) groups, and hypothyroidism was induced with 6-propyl-2-thiouracil (PTU) for three months. In the last month, half of the hypothyroid animals received Kp10. Testis samples were collected for enzymatic, immunohistochemical and/or gene evaluation of mediators of oxidative stress (TBARs, lipid hydroperoxides (LOOH), ROS, peroxynitrite, SOD, CAT and GPX), endoplasmic reticulum stress (GRP78, ATF6, PERK, CHOP, HO-1 and sXBP1) and antiapoptocytes (BCL-2). Hypothyroidism increased apoptosis index, TBARS and LOOH concentrations, and reduced testicular gene expression of Sod1 , Sod2 and Gpx1 , as well as the expression of Grp78 , Atf6 , Ho1 and Chop . Treatment with Kp10, in turn, reduced testicular apoptosis and the production of peroxynitrite, while increased SOD1 and GPX ½ expression, and enzymatic activity of CAT, but did not affect the lower expression of UPR mediators caused by hypothyroidism. This study demonstrated that hypothyroidism causes oxidative stress and dysregulated the UPR pathway in rat testes and that, although Kp10 does not influence the low expression of UPR mediators, it improves the testicular redox status, configuring it as an important antioxidant factor in situations of thyroid dysfunction.

Objectives: The aim of this study was to evaluate the expression profile of sex steroid receptors and redox mediators in the uterus of domestic cats with pyometra., Methods: Twelve cats were used and divided into groups: (1) non-gestational healthy diestrus (n = 7) and (2) pyometra (n = 5). The plasma profiles of estradiol and progesterone (P 4 ) as well as uterine expression levels of estradiol alpha (ERα), progesterone (PR) and androgen (AR) receptors, of the antioxidant enzymes superoxide dismutase 1 (SOD1), catalase and glutathione peroxidase 1 (GPX1), and of the oxidative damage marker 8-hydroxy-2'-deoxyguanosine (8-OHdG) were evaluated., Results: Cats with pyometra showed higher plasma P 4 levels and increased uterine messenger RNA (mRNA) and protein expression of ERα and PR, mainly in the glandular epithelium for ERα and in stromal and myometrial cells for PR. In addition, there was an increase in 8-OHdG immunostaining and GPX1 mRNA and protein expression in cats with pyometra compared with those in non-gestational diestrus, while catalase showed a reduction in endometrial immunostaining in cats with pyometra. There were no differences in uterine AR and SOD1 expression between the groups., Conclusion and Relevance: The findings of this study showed that pyometra is associated with oxidative stress in the uterus of domestic cats and alterations of the profile of sex steroid receptors, especially ERα and PR, and of antioxidant enzymes, suggesting that changes in these mediators may play a role with the etiopathogenesis of this disease., Competing Interests: Conflict of interestThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Toxoplasmosis is a significant public health concern with limited therapeutic options. The medicines for malaria venture (MMV) developed the pandemic response box (PRB) containing 400 drug-like molecules with broad pathogen activity. The aim of this work is to evaluate PRB compounds for their anti- Toxoplasma gondii activity and identify promising candidates for further evaluation. Screening identified 42 selective compounds with half effective concentration (EC 50 ) ranging from 2.4 to 913.1 nm and half cytotoxic concentration (CC 50 ) ranging from 6 μm to >50 μm. Selectivity index (SI) values (CC 50 /EC 50 ) ranged from 11 to 17 708. Based on its in silico and in vitro profile and its commercial availability, RWJ-67657 was selected for further studies. Molecular docking analysis showed RWJ-67657 is predicted to bind to T. gondii p38 mitogen-activated protein kinase (TgMAPK). Oral administration of RWJ-67657 (20 mg kg day −1 /10 days) significantly reduced parasite burden in chronically infected mice compared to mock-treated group ( P < 0.01). These findings highlight the PRB as a promising source for anti- T. gondii compounds, with several showing favourable drug properties, including MMV1634492, MMV002731, MMV1634491, MMV1581551, MMV011565, MMV1581558, MMV1578577, MMV233495 and MMV1580482, firstly described here as anti- T. gondii agents. RWJ-67657 emerges as a valuable drug candidate for experimental chronic cerebral toxoplasmosis therapy.

Sex steroids and antioxidant enzymes modulate uterine and placental physiology. Failures in the expression, signaling, and/or secretion of these mediators are associated with female infertility and gestational problems. However, there is no data on the expression profile of receptors for sex steroids and antioxidant enzymes in the maternal-fetal interface of domestic cats. Uterus and placenta samples from non-pregnant diestrus cats and cats in mid- and late pregnancy were used to analyze the protein and gene expression of the receptors for estrogen alpha (ERα), progesterone (PR), and androgen (AR) and the antioxidant enzymes superoxide dismutase 1 (SOD1), catalase, and glutathione peroxidase 1 (GPX1) by immunohistochemistry and qPCR. Higher uterine expression of ERα, Pr, and Sod1 was observed in the pregnant cats, especially in mid-pregnancy, compared to non-pregnant diestrus cats, as well as reduced endometrial catalase immunostaining. In the placenta, the mRNA expression of Erα, Pr, Ar, and Gpx1 was higher in late pregnancy in relation to mid-pregnancy. Moreover, weak or no placental expression was observed for catalase in mid- and late pregnancy, while strong immunostaining was observed for AR in trophoblasts and decidual cells in mid-pregnancy. The findings of this study demonstrated that pregnancy in female cats increases the uterine expression of sex steroid receptors and antioxidant enzymes, and that the placental expression of these mediators varies according to gestational age., Competing Interests: Declaration of competing interest The authors have nothing to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

We evaluated whether the administration of kisspeptin-10 (Kp10) is capable of restoring gonadal function in hypothyroid male rats. Hypothyroidism was induced with 6-propyl-2-thiouracil (PTU) for three months. In the last month, half of the hypothyroid animals were treated with Kp10. Hypothyroidism reduced testicular and sex gland mass, decreased the proliferation of the seminiferous epithelium, and compromised sperm morphology, motility, and vigor. A decrease in plasma LH and testosterone levels and an increase in prolactin secretion were observed in the hypothyroid rats. Hypothyroidism reduced Kiss1 and Kiss1r protein and gene expression and Star and Cyp11a1 mRNA levels in the testis. Furthermore, it reduced Lhb, Prl, and Drd2 and increased Tshb and Gnrhr expression in the pituitary. In the hypothalamus, hypothyroidism increased Pdyn and Kiss1r while reducing Gnrh1. Kp10 treatment in hypothyroid rats restored testicular and seminal vesicle morphology, improved sperm morphology and motility, reversed high prolactin levels, and increased LH and testosterone levels. In addition, Kp10 increased testicular expression of Kiss1, Kiss1r, Fshr, and Nr5a1 and pituitary Kiss1 expression. Our findings describe the inhibitory effects of hypothyroidism on the male gonadal axis and sperm quality and demonstrate that Kp10 treatment reverses high prolactin levels and improves gonadal function and sperm quality in hypothyroid rats., (© 2023. Springer Nature Limited.)

Although current evidence suggests increased risk of obesity, insulin resistance, and metabolic alterations in patients with polycystic ovary syndrome (PCOS), especially of a hyperandrogenic phenotype, the impact of each one of these variables on muscle mass remains uncertain. In this case-control study, we evaluated clinical and hormonal characteristics related to lean body mass according to the different PCOS phenotypes. We performed clinical, metabolic, and hormonal assessments and evaluated body compartments by dual-energy X-ray absorptiometry in 133 women of reproductive age. Creatinine served as an indirect marker of lean mass. Median age was 28 (range, 17-37) years. Women with phenotypes A and B (n = 59) had higher body mass index (BMI) and metabolic syndrome prevalence than those with phenotype C (n = 23) and controls (n = 51) (p<0.005). Women with phenotypes A and B also had higher Ferriman-Gallwey score (p<0.001), insulin levels (p = 0.006), HOMA-IR (p = 0.008), testosterone (p = 0.008), free androgen index (FAI) (p<0.001), fat mass index (FMI) (p = 0.015), android-to-gynoid fat ratio (p = 0.036), and bone mineral density (BMD) at lumbar spine (p = 0.027) and total femur (p = 0.013) than controls. Median appendicular lean mass index (ALMI) was higher in phenotypes A and B than in controls (7.01 [IQR, 6.33-8.02] vs. 6.69 [IQR, 5.94-7.09], p = 0.024), but it did not differ significantly from that in phenotype C (6.60 [IQR, 6.16-7.22], p = 0.222). Even after adjusting for BMI, ALMI correlated positively with creatinine in women with phenotypes A and B (rho = 0.319, p = 0.023) but not in those with phenotype C (p = 0.238) or controls (p = 0.097). In multivariate linear regression analyses, ALMI was positively associated with insulin, FAI, FMI, and total femur BMD. The present results suggest that fasting insulin, FAI, fat mass, and total femur BMD were positively associated with increased lean mass in women with PCOS phenotypes A and B., Competing Interests: Competing interests: the authors declare that no competing interests exist., (Copyright: © 2023 Fighera et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Toxoplasmosis, caused by the obligate intracellular parasite Toxoplasma gondii, affects about one-third of the world's population and can cause severe congenital, neurological and ocular issues. Current treatment options are limited, and there are no human vaccines available to prevent transmission. Drug repurposing has been effective in identifying anti-T. gondii drugs. In this study, the screening of the COVID Box, a compilation of 160 compounds provided by the "Medicines for Malaria Venture" organization, was conducted to explore its potential for repurposing drugs to combat toxoplasmosis. The objective of the present work was to evaluate the compounds' ability to inhibit T. gondii tachyzoite growth, assess their cytotoxicity against human cells, examine their absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties, and investigate the potential of one candidate drug through an experimental chronic model of toxoplasmosis. Early screening identified 29 compounds that could inhibit T. gondii survival by over 80% while keeping human cell survival up to 50% at a concentration of 1 μM. The Half Effective Concentrations (EC50) of these compounds ranged from 0.04 to 0.92 μM, while the Half Cytotoxic Concentrations (CC50) ranged from 2.48 to over 50 μM. Almitrine was chosen for further evaluation due to its favorable characteristics, including anti-T. gondii activity at nanomolar concentrations, low cytotoxicity, and ADMET properties. Administering almitrine bismesylate (Vectarion®) orally at dose of 25 mg/kg/day for ten consecutive days resulted in a statistically significant (p < 0.001) reduction in parasite burden in the brains of mice chronically infected with T. gondii (ME49 strain). This was determined by quantifying the RNA of living parasites using real-time PCR. The presented results suggest that almitrine may be a promising drug candidate for additional experimental studies on toxoplasmosis and provide further evidence of the potential of the MMV collections as a valuable source of drugs to be repositioned for infectious diseases., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 dos Santos et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Sex steroids and antioxidant enzymes are important in female sexual development and adequate modulation of the estrous cycle, pregnancy, and fetal development. Therefore, modifications in its signaling or expression in the genital system are associated with reproductive dysfunctions. However, the spatial-temporal expression profile of receptors for sex steroids and antioxidant enzymes in the uterus of domestic cats throughout the estrous cycle needs to be studied. Cats in proestrus/estrus (N = 6), diestrus, (N = 7), and anestrus (N = 6) were used to evaluate the uterine expression of estrogen alpha (ERα), progesterone (PR), and androgen (AR) receptors and of the antioxidant enzymes superoxide dismutase 1 (SOD1), catalase and glutathione peroxidase 1 (GPX1) by immunohistochemistry and qPCR. The uterus of cats in diestrus showed lower protein and mRNA expression of ERα and PR compared to proestrus/estrus and anestrus, mainly in the luminal and glandular epithelium and myometrium, different from catalase and SOD1, which showed higher expression in diestrus in relation to other phases of the cycle. GPX1, on the other hand, showed lower uterine gene expression in diestrus compared to proestrus/estrus and anestrus. No significant differences in AR expression were observed. In conclusion, ERα and PR sex steroid receptors and antioxidant enzymes are expressed differently in the uterus of domestic cats during the estrous cycle., Competing Interests: Declaration of competing interest The authors have nothing to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Context: Proliferation, differentiation, migration and apoptosis of trophoblastic cells are influenced by hypoxia, as well as adequate modulation of oxidative stress and the unfolded protein response (UPR) pathway., Aims: We aimed to evaluate the expression profile of redox and UPR mediators in the placenta of rats throughout pregnancy., Methods: Placental expression of hypoxia-inducible factor 1α (HIF1α), 8-Hydroxy-2'-deoxyguanosine (8-OHdG), superoxide dismutase 1 (SOD1), glutathione peroxidase (GPX), catalase (Cat), activating transcription factor 6 (ATF6), protein kinase RNA-like endoplasmic reticulum kinase (PERK), 78 kD glucose-regulated protein (GRP78) and C/EBP-homologous protein (CHOP), as well as reactive oxygen species (ROS) and peroxynitrite production, were evaluated in Wistar rats on the 10th, 12th, 14th, 16th and 18th day of pregnancy (DP)., Key Results: Increased immunostaining of HIF1α was observed on the 16th and 18th DP, while 8-OHdG and ROS production were greater on the 14th DP. SOD1 and Cat had increased immunostaining on the 14th and 18th DP, while staining of GPX1/2, GRP78 and CHOP was greater on the 18th DP. With regard to gene expression, Hif1α and Sod1 showed increased mRNA expression on the 12th and 16th DP, while Gpx1 had increased expression on the 10th and 16th DP. Cat , Perk and Grp78 gene expression was greater on the 14th DP, unlike Atf6 , which showed greater expression on the 12th DP. In contrast, Chop maintained increased expression from the 12th to the 18th DP., Conclusions: The placental expression of redox and UPR mediators in rats is influenced by gestational age, with greater expression in periods of greater HIF1α and 8-OHdG expression and at the end of the pregnancy., Implications: This study provides data on the physiological modulation of redox and UPR mediators during placental development in rats.

Background: Exercise training improves physical capacity in patients with heart failure with reduced ejection fraction (HFrEF), but the mechanisms involved in this response is not fully understood. The aim of this study was to determine if physical capacity increase in patients HFrEF is associated with muscle sympathetic nerve activity (MSNA) reduction and muscle blood flow (MBF) increase., Methods: The study included 124 patients from a 17-year database, divided according to exercise training status: 1) exercise-trained (ET, n = 83) and 2) untrained (UNT, n = 41). MSNA and MBF were obtained using microneurography and venous occlusion plethysmography, respectively. Physical capacity was evaluated by cardiopulmonary exercise test. Moderate aerobic exercise was performed 3 times/wk. for 4 months., Results: Exercise training increased peak oxygen consumption (V̇O 2 , 16.1 ± 0.4 vs 18.9 ± 0.5 mL·kg -1 ·min -1 , P < 0.001), LVEF (28 ± 1 vs 30 ± 1%, P = 0.027), MBF (1.57 ± 0.06 vs 2.05 ± 0.09 mL.min -1 .100 ml -1 , P < 0.001) and muscle vascular conductance (MVC, 1.82 ± 0.07 vs 2.45 ± 0.11 units, P < 0.001). Exercise training significantly decreased MSNA (45 ± 1 vs 32 ± 1 bursts/min, P < 0.001). The logistic regression analyses showed that MSNA [(OR) 0.921, 95% CI 0.883-0.962, P < 0.001] was independently associated with peak V̇O 2 ., Conclusions: The increase in physical capacity provoked by aerobic exercise in patients with HFrEF is associated with the improvement in MSNA., Competing Interests: Declaration of Competing Interest All authors have reported that there is no relationship with industry or financial associations, which might pose a conflict of interest in connection to this article., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: COVID-19 has overwhelmed health services globally. Oral antiviral therapies are licensed worldwide, but indications and efficacy rates vary. We aimed to evaluate the safety and efficacy of oral favipiravir in patients hospitalised with COVID-19., Methods: We conducted a multicentre, open-label, randomised controlled trial of oral favipiravir in adult patients who were newly admitted to hospital with proven or suspected COVID-19 across five sites in the UK (n=2), Brazil (n=2) and Mexico (n=1). Using a permuted block design, eligible and consenting participants were randomly assigned (1:1) to receive oral favipiravir (1800 mg twice daily for 1 day; 800 mg twice daily for 9 days) plus standard care, or standard care alone. All caregivers and patients were aware of allocation and those analysing data were aware of the treatment groups. The prespecified primary outcome was the time from randomisation to recovery, censored at 28 days, which was assessed using an intention-to-treat approach. Post-hoc analyses were used to assess the efficacy of favipiravir in patients aged younger than 60 years, and in patients aged 60 years and older. The trial was registered with clinicaltrials.gov, NCT04373733., Findings: Between May 5, 2020 and May 26, 2021, we assessed 503 patients for eligibility, of whom 499 were randomly assigned to favipiravir and standard care (n=251) or standard care alone (n=248). There was no significant difference between those who received favipiravir and standard care, relative to those who received standard care alone in time to recovery in the overall study population (hazard ratio [HR] 1·06 [95% CI 0·89-1·27]; n=499; p=0·52). Post-hoc analyses showed a faster rate of recovery in patients younger than 60 years who received favipiravir and standard care versus those who had standard care alone (HR 1·35 [1·06-1·72]; n=247; p=0·01). 36 serious adverse events were observed in 27 (11%) of 251 patients administered favipiravir and standard care, and 33 events were observed in 27 (11%) of 248 patients receiving standard care alone, with infectious, respiratory, and cardiovascular events being the most numerous. There was no significant between-group difference in serious adverse events per patient (p=0·87)., Interpretation: Favipiravir does not improve clinical outcomes in all patients admitted to hospital with COVID-19, however, patients younger than 60 years might have a beneficial clinical response. The indiscriminate use of favipiravir globally should be cautioned, and further high-quality studies of antiviral agents, and their potential treatment combinations, are warranted in COVID-19., Funding: LifeArc and CW+., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Gestational diseases such as preeclampsia and gestational diabetes cause inflammasome activation and pyroptosis in the placenta and changes in placental kisspeptin levels. Although maternal hypothyroidism also reduces the kisspeptin/Kiss1R system at the maternal-fetal interface, there is still no information on whether this dysfunction causes inflammasome activation and pyroptosis in the placenta or influences the modulatory role of kisspeptin in these processes. This study aimed to evaluate whether hypothyroidism activates the inflammasome-NLRP3 pathway and pyroptosis at the maternal-fetal interface of rats and whether kisspeptin can modulate these processes. Hypothyroidism was induced in Wistar rats by the administration of propylthiouracil. Kisspeptin-10 (Kp10) treatment began on the 8th day of gestation (DG). Gene and/or protein expressions of NLRP3, Caspase 1, IL-1β, IL-18, and Gasdermin D (Gsmd) were evaluated in the deciduae and placentae at the 18th DG. Hypothyroidism increased the decidual and placental stainings of NLRP3, IL-1β, and Gasdermin D, and increased the gene expressions of Nlrp3 , Ilβ , and Il18 in the placenta and of Gsmd in the decidua. Treatment with Kp10 suppressed the increase in NLRP3/ Nlrp3 , IL-1β, Il18 , and Gasdermin D/ Gsmd caused by hypothyroidism at the maternal-fetal interface. However, Kp10 increased the placental gene expressions of Casp1 and Il1β . The findings demonstrated that maternal hypothyroidism activated the inflammasome-NLRP3 pathway and pyroptosis at the maternal-fetal interface of rats and that treatment with Kp10 was able to block these processes, thus suggesting that kisspeptin analogues may be promising in the treatment of gestational diseases that involve inflammasome activation and pyroptosis.

Background: Childbirth via cesarean delivery can prevent intrapartum vertical transmission for women who are not virally suppressed at the time of delivery. Few studies have compared cesarean delivery trends between women living with HIV and women without HIV and have examined the role of cesarean delivery in the prevention of vertical transmission in the era of potent combination antiretroviral therapy., Objective: We hypothesized that the cesarean delivery rate is high in women living with HIV compared with women without HIV and that cesarean delivery usage decreases over time among women living with HIV with advances in combined antiretroviral therapy in a country with a high national cesarean delivery rate. This study aimed (1) to evaluate cesarean delivery trends in women with and without HIV and (2) to examine its role in preventing vertical transmission among women living with HIV in a setting of free, universal combined antiretroviral therapy coverage in a retrospective cohort of nearly 56,000 deliveries at a major referral institution in a city with the highest prevalence of maternal HIV in Brazil., Study Design: Data from maternal-infant pairs from January 1, 2008, to December 31, 2018, were extracted. Cesarean delivery rates were compared using the Pearson chi-square test. Cesarean delivery predictors were evaluated by multivariate log-linear Poisson regression using a generalized estimating equations approach. HIV viral suppression was defined as a viral load of <1000 copies/ml at delivery. HIV vertical transmission was determined following national guidelines., Results: Over 11 years, 48,688 pregnancies occurred in 40,375 women; HIV seroprevalence was 2.7%; 18,886 cesarean deliveries (38.8%) were performed; 47.7% of women living with HIV and 38.6% of women without HIV underwent cesarean delivery ( P <.001). Although HIV was associated with cesarean delivery (adjusted relative risk, 1.17 [95% confidence interval, 1.05-1.29]), women living with HIV with vertical transmission achieved similar cesarean delivery rates (36.7%) as women without HIV (39.8%) in 2018. Cesarean delivery in women living with HIV with an unknown viral load at delivery (42.6%) did not increase over time. HIV vertical transmission rate was 2.2%, the highest in women living with HIV with an unknown viral load (8.4%) vs women living with HIV without vertical transmission (4.1%) and women living with HIV with vertical transmission (0.5%) ( P <.001)., Conclusion: In the HIV epicenter of Brazil, women living with HIV with vertical transmission had fewer surgical deliveries, likely because of the use of potent combination antiretroviral therapy. Nearly half of the women living with HIV with an unknown viral load did not undergo cesarean delivery, a potential missed opportunity for the prevention of HIV vertical transmission., (© 2023 The Authors.)

Objectives: The aim of this study was to explore body composition parameters and hormone levels as risk factors for low bone mass (osteopenia/osteoporosis) in postmenopausal women., Methods: We analyzed biorepository samples from 139 postmenopausal women with no clinical evidence of cardiovascular disease. Inclusion criteria were menopause occurring after 40 years of age and no use of hormone therapy in the past 3 months. Bone mineral density and body composition were assessed by dual-energy x-ray absorptiometry. Sex hormone-binding globulin (SHBG) and follicle-stimulating hormone (FSH) levels were measured in all participants. Serum estradiol was measured by gas chromatography/tandem mass spectrometry in a subset of 57 participants. Free estrogen index was calculated by dividing estradiol by SHBG × 100., Results: Body mass index (25.0 [22.5-26.5] vs 27.7 [26.6-31.9] kg/m 2 , P < 0.001), estradiol (3.0 [2.7-4.5] vs 6.0 [2.7-15.0] pg/mL, P = 0.006), waist circumference (84 ± 9 vs 93 ± 12 cm, P < 0.001), appendicular lean mass (ALM) (15.739 ± 2.129 vs 17.184 ± 2.104 kg, P = 0.001), and fat mass index (9.36 [7.29-11.43] vs 11.38 [9.95-15.33] kg/m 2 , P < 0.001) were lower in women with low bone mass by dual-energy x-ray absorptiometry. Univariate analysis showed that free estrogen index, time since menopause, SHBG, and fat mass were significant predictors of low bone mass, and ALM was a significant predictor against low bone mass. Appendicular lean mass persisted as an independent predictor against low bone mass in multivariate models with fat mass and SHBG. In turn, fat mass was no longer significant in this multivariate model after inclusion of SHBG. No association of FSH with low bone mass was observed., Conclusions: Appendicular lean mass was a significant independent predictor against low bone mass in postmenopausal women. Further prospective studies are needed to investigate whether lean mass, fat mass, and FSH have a direct effect on bone mass in postmenopausal women, adding to the consequences of hypoestrogenism in this group., Competing Interests: Financial disclosure/conflicts of interest: None reported., (Copyright © 2022 by The North American Menopause Society.)

Boana comprises a diverse genus of Neotropical treefrogs, currently rearranged into seven taxonomic species groups. Although cytogenetic studies have demonstrated diversity in its representatives, the chromosomal mapping of repetitive DNA sequences is still scarce. In this study, Boana albopunctata, Boana faber, and Boana prasina were subjected to in situ localization of different repetitive DNA units to evaluate trends of chromosomal evolution in this genus. Boana faber and B. prasina had 2n=24 chromosomes, while B. albopunctata has 2n=22 and an intra-individual variation related to the presence/absence of one B chromosome. The location of 45S rDNA sites was different in the analyzed karyotypes, corroborating with what was found in the distinct phylogenetic groups of Boana. We presented the first description of 5S rDNA in a Boana species, which showed markings resulting from transposition/translocation mechanisms. In situ localization of microsatellite loci proved to be a helpful marker for karyotype comparison in Boana, commonly with cis accumulation in the heterochromatin. On the other hand, genomic dispersion of microsatellites may be associated with hitchhiking effects during the spreading of transposable elements. The obtained results corroborated the independent diversification of these lineages of species from three distinct phylogenetic groups of Boana.

Background: Hypothyroidism causes ovarian dysfunction and infertility in women, in addition to being associated with hyperprolactinemia and reduced hypothalamic expression of kisspeptin (Kp). However, it remains unknown whether and how Kp is able to reverse the ovarian dysfunction caused by hypothyroidism. Methods: Hypothyroidism was induced in adult female Wistar rats using 6-propyl-2-thiouracil for 3 months. In the last month, half of the animals received Kp10. Blood samples were collected for dosage of free thyroxine, thyrotropin (TSH), luteinizing hormone (LH), prolactin (PRL), progesterone (P 4 ), and estradiol (E 2 ), and uteruses and ovaries were collected for histomorphometry. Body and ovarian weight and the number of corpora lutea were also evaluated. Half of the brains were evaluated by immunohistochemistry to Kp, and the other half had the arcuate nucleus of hypothalamus (ARC) and preoptic area microdissected for gene evaluation of Kiss1, Nkb, Pdyn, and Gnrh1. The pituitary gland and corpora lutea were also dissected for gene evaluation. Results: Hypothyroidism kept the animals predominantly acyclic and promoted a reduction in ovarian weight, number of corpora lutea, endometrial thickness, number of endometrial glands, and plasma LH, in addition to increasing the luteal messenger RNA (mRNA) expression of Star and Cyp11a1 and reducing 20αHsd . An increase in plasma PRL and P 4 levels was also caused by hypothyroidism. Kp immunoreactivity and Kiss1 and Nkb mRNA levels in the ARC and Kiss1 in the anteroventral periventricular nucleus of hypothalamus were reduced in hypothyroid rats. Hypothyroid animals had lower pituitary gene expression of Gnrhr , Lhb , Prl , and Drd2 , and an increase in Tshb . The treatment with Kp10 restored estrous cyclicality, plasma LH, ovarian and uterine morphology, and Cyp11a1 , 3βHsd , and 20αHsd mRNA levels in the corpora lutea. Kp10 treatment did not alter gene expression for Kiss1 or Nkb in the ARC of hypothyroid rats. Nevertheless, Kp10 increased Lhb mRNA levels and reduced Tshb in the pituitary compared with the hypothyroid group. Conclusions: The present findings characterize the inhibitory effects of hypothyroidism on the hypothalamic-pituitary-gonadal axis in female rats and demonstrate that Kp10 is able to reverse the ovarian dysfunction caused by hypothyroidism, regardless of hyperprolactinemia.

Background: Pregnancy loss is poorly understood, but infection may be a risk factor. Few studies have evaluated pregnancy loss among women living with HIV in the era of potent combination antiretroviral therapy., Objective: We hypothesize that maternal HIV and syphilis infection lead to increased risk of pregnancy loss, including both miscarriage and stillbirth. This study aimed to assess trends and possible predictors of spontaneous miscarriage and stillbirth among women living with HIV in a cohort of nearly 56,000 deliveries at a major referral institution in a city with the highest prevalence of HIV in Brazil., Study Design: Data from hospital records for women delivering from January 1, 2008 to December 31, 2018 were reviewed. Rates of stillbirth, miscarriage, and any pregnancy loss were compared using the Pearson chi-square test. Predictors of pregnancy loss were evaluated by robust univariate log-linear Poisson regression using a generalized estimating equations approach., Results: A total of 55,844 pregnancies were included in the analysis, with 54,308 pregnancies from 43,502 women without HIV and 1536 pregnancies from 1186 women living with HIV (seroprevalence of maternal HIV: 2.7%). Overall, 1130 stillbirths (2.0%) and 6558 miscarriages (11.7%) occurred. Any pregnancy loss was similar in both groups (13.8% in women without and 14.1% in women with HIV; P =.733). Stillbirth was higher among women living with HIV (3.4%) than among women without HIV (2.0%; P <.001), but there was no difference in overall miscarriage rates (10.7% in women with vs. 11.8% in women without HIV; P =.188). Women living with HIV had higher miscarriage rates between 12 and 20 weeks than women without HIV (34.8% vs 23.7%; P =.001), likely because of syphilis coinfection. Stillbirth rates were higher for women living with HIV from 2008 to 2014; however, a steady plateau was reached from 2014 to 2018, mirroring stillbirth rates in women without HIV. Maternal HIV infection did not increase the risk of miscarriage (relative risk, 0.90; 95% confidence interval, 0.77-1.05) or any pregnancy loss (relative risk, 1.00; 95% confidence interval, 0.88-1.15), but was associated with stillbirth (relative risk, 1.65; 95% confidence interval, 1.23-2.21). Maternal syphilis was associated with any pregnancy loss (relative risk, 1.24; 95% confidence interval, 1.11-1.38) and stillbirth (relative risk, 3.39; 95% confidence interval, 2.77-4.14), but not miscarriage (relative risk, 0.91; 95% confidence interval, 0.80-1.04)., Conclusion: In the era of combination antiretroviral therapy, there was no difference in miscarriage rates between women with and without HIV. HIV was associated with stillbirth risk but improved over time. Maternal syphilis was significantly associated with any pregnancy loss and stillbirth in all women. Syphilis is likely the main driver of pregnancy loss in women living with HIV in Brazil., (© 2022 The Authors.)

Maternal hypothyroidism is associated with pre-eclampsia and intrauterine growth restriction, gestational diseases involving oxidative stress (OS) and endoplasmic reticulum stress (ERS) in the placenta. However, it is not known whether hypothyroidism also causes OS and ERS at the maternal-fetal interface. The aim was to evaluate the fetal-placental development and the expression of mediators of OS and of the unfolded protein response (UPR) in the maternal-fetal interface of hypothyroid rats. Hypothyroidism was induced in Wistar rats with propylthiouracil and the fetal-placental development and placental and decidual expression of antioxidant, hypoxia, and UPR mediators were analyzed at 14 and 18 days of gestation (DG), as well the expression of 8-OHdG and MDA, and reactive oxygen species (ROS) and peroxynitrite levels. Hypothyroidism reduced fetal weight at 14 and 18 DG, in addition to increasing the percentage of fetal death and reducing the weight of the uteroplacental unit at 18 DG. At 14 DG, there was greater decidual and/or placental immunostaining of Hif1α, 8-OHdG, MDA, SOD1, GPx1/2, Grp78 and CHOP in hypothyroid rats, while there was a reduction in placental and/or decidual gene expression of Sod1, Gpx1, Atf6, Perk, Ho1, Xbp1, Grp78 and Chop in the same gestational period. At 18 DG, hypothyroidism increased the placental ROS levels and the decidual and/or placental immunostaining of HIF1α, 8-OHdG, MDA, ATF4, GRP78 and CHOP, while it reduced the immunostaining and enzymatic activity of SOD1, CAT, GST. Hypothyroidism increased the placental mRNA expression of Hifα, Nrf2, Sod2, Gpx1, Cat, Perk, Atf6 and Chop at 18 DG, while decreasing the decidual expression of Sod2, Cat and Atf6. These findings demonstrated that fetal-placental restriction in female rats with hypothyroidism is associated with hypoxia and dysregulation in placental and decidual expression of UPR mediators and antioxidant enzymes, and activation of oxidative stress and endoplasmic reticulum stress at the maternal-fetal interface., Competing Interests: Declaration of competing interest The author shave declared that no conflict interest exists., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: The effect of pneumococcal vaccination of mothers with human immunodeficiency virus (HIV) on infant responses to childhood vaccination has not been studied. We compared the immunogenicity of 10-valent pneumococcus conjugate vaccine (PCV-10) in HIV-exposed uninfected infants born to mothers who received PCV-10, 23-valent pneumococcus polysaccharide vaccine (PPV-23), or placebo during pregnancy., Methods: Antibody levels against 7 serotypes were measured at birth, before the first and second doses of PCV-10m and after completion of the 2-dose regimen in 347 infants, including 112 born to mothers who received PPV-23, 112 who received PCV-10, and 119 who received placebo during pregnancy. Seroprotection was defined by antibody levels ≥0.35 µg/mL., Results: At birth and at 8 weeks of life, antibody levels were similar in infants born to PCV-10 or PPV-23 recipients and higher than in those born to placebo recipient. After the last dose of PCV-10, infants in the maternal PCV-10 group had significantly lower antibody levels against 5 serotypes than those in the maternal PPV-23 group and against 3 serotypes than those in the maternal placebo group, and they did not have higher antibody levels against any serotype. The seroprotection rate against 7 serotypes was 50% in infants in the maternal PCV-10 group, compared with 71% in both of the maternal PPV-23 and placebo groups (P < .001)., Conclusions: Administration of PCV-10 during pregnancy was associated with decreased antibody responses to PCV-10 and seroprotection rates in infants. Considering that PCV-10 and PPV-23 had similar immunogenicity in pregnant women with HIV and that administration of PPV-23 did not affect the immunogenicity of PCV-10 in infants, PPV-23 in pregnancy may be preferred over PCV-10., Competing Interests: Potential conflicts of interest. M. M. M. P. and G. D. report provision of PCV-10 by donation from Centro de Vigilância Epidemiológica da Secretaria da Saúde do Estado de São Paulo, São Paulo, Brazil. L. L. reports that Westat was the contract research organization contracted through the National Institutes of Health (NIH) for a task order for the current study. S. I. P. reports receipt of personal fees from Merck, Sanofi, and Pfizer; investigator-initiated grants from the NIH and Pfizer and Merck Vaccines to study surveillance of invasive pneumococcal disease, host defenses against Streptococcus pneumoniae, and the impact of severe acute respiratory syndrome coronavirus 2 on nasopharyngeal microbiome; and consulting fees from Pfizer and Merck Vaccine for participation in advisory board meetings, consulting on research projects at PAI Life Sciences and EVIDERA, and participation on a data safety and monitoring board for next-generation PCVs for Sanofi Pasteur. N. C. is employed by the NIH. A. W. has received grants from the NIH, GlaxoSmithKline, Janssen and Merck; consulting fees from Merck; and payment or honoraria from Merck. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Hirsutism is defined as the presence of terminal hair with male pattern distribution in women. While in the general population, hirsutism affects around 4-11% of women, it is the main manifestation of hyperandrogenism in women with polycystic ovary syndrome (PCOS), with a prevalence estimated at 65-75%. Hirsutism in PCOS is associated with both androgen excess and individual response of the pilosebaceous unit to androgens. The modified Ferriman-Gallwey (mFG) scoring system has been widely used in clinical practice to visually score excessive terminal hair, thus standardizing hirsutism evaluation and facilitating data comparison. Although a universal mFG score cutoff would be useful for comparisons, ethnic variations, as well as skin type and other factors, should be considered when evaluating hirsutism in distinct populations. In turn, androgen levels, measured by conventional techniques, have been shown to correlate poorly with the severity of hirsutism. Indeed, while most women with PCOS and hirsutism also have higher than reference values for serum androgen levels, some of them may not present with biochemical hyperandrogenism, representing a challenge to the diagnosis of PCOS. In this article, we critically review this not uncommon condition in women with PCOS presenting with hirsutism but normal androgen levels.

Maternal hypothyroidism is associated with fetal growth restriction, placental dysfunction, and reduced kisspeptin/Kiss1R at the maternal-fetal interface. Kisspeptin affects trophoblastic migration and has antioxidant and immunomodulatory activities. This study aimed to evaluate the therapeutic potential of kisspeptin in the fetal-placental dysfunction of hypothyroid Wistar rats. Hypothyroidism was induced by daily administration of propylthiouracil. Kisspeptin-10 (Kp-10) treatment was performed every other day or daily beginning on day 8 of gestation. Feto-placental development, placental histomorphometry, and expression levels of growth factors (VEGF, PLGF, IGF1, IGF2, and GLUT1), hormonal (Dio2) and inflammatory mediators (TNFα, IL10, and IL6), markers of hypoxia (HIF1α) and oxidative damage (8-OHdG), antioxidant enzymes (SOD1, Cat, and GPx1), and endoplasmic reticulum stress mediators (ATF4, GRP78, and CHOP) were evaluated on day 18 of gestation. Daily treatment with Kp-10 increased free T3 and T4 levels and improved fetal weight. Both treatments reestablished the glycogen cell population in the junctional zone. Daily treatment with Kp-10 increased the gene expression levels of Plgf , Igf1 , and Glut1 in the placenta of hypothyroid animals, in addition to blocking the increase in 8-OHdG and increasing protein and/or mRNA expression levels of SOD1, Cat, and GPx1. Daily treatment with Kp-10 did not alter the higher protein expression levels of VEGF, HIF1α, IL10, GRP78, and CHOP caused by hypothyroidism in the junctional zone compared to control, nor the lower expression of Dio2 caused by hypothyroidism. However, in the labyrinth zone, this treatment restored the expression of VEGF and IL10 and reduced the GRP78 and CHOP immunostaining. These findings demonstrate that daily treatment with Kp-10 improves fetal development and placental morphology in hypothyroid rats, blocks placental oxidative damage, and increases the expression of growth factors and antioxidant enzymes in the placenta., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Santos, dos Anjos Cordeiro, Santos, Barbosa, Mendonça, Santos, de Macedo, de Lavor, Szawka, Serakides and Silva.)

Alterations of circulating and placental levels of kisspeptin have been associated with gestational diseases. However, there are still no studies on the placental and decidual expression of Kiss1 and its receptor Kiss1r in maternal hypothyroidism, which is the aim of this work. We demonstrate that the fetoplacental restriction caused by hypothyroidism in rats is associated with a reduction in the Kiss1r expression and reduced Kiss1 and Kiss1r mRNA levels in the decidua and/or placenta. This demonstrate that fetoplacental restriction in hypothyroid rats is linked with a suppression of the kisspeptin/Kiss1r system at the maternal-fetal interface., (Copyright © 2022 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier B.V. All rights reserved.)

Introduction: ACTG A5288 was a strategy trial conducted in diverse populations from multiple continents of people living with HIV (PLWH) failing second-line protease inhibitor (PI)-based antiretroviral therapy (ART) from 10 low- and middle-income countries (LMICs). Participants resistant to lopinavir (LPV) and/or multiple nucleotide reverse transcriptase inhibitors started on third-line regimens that included raltegravir (RAL), darunavir/ritonavir (DRV/r) and/or etravirine (ETR) according to their resistance profiles. At 48 weeks, 87% of these participants achieved HIV-1 RNA ≤200 copies/ml. We report here long-term outcomes over 144 weeks., Methods: Study participants were enrolled from 2013 to 2015, prior to the availability of dolutegravir in LMICs. "Extended Follow-up" of the study started after the last participant enrolled had reached 48 weeks and included participants still on antiretroviral (ARV) regimens containing RAL, DRV/r and/or ETR at that time. RAL, DRV/r and ETR were provided for an additional 96 weeks (giving total follow-up of ≥144 weeks), with HIV-1 RNA measured at 48 and 96 weeks and CD4 count at 96 weeks after entry into Extended Follow-up. Proportion of participants with HIV-1 RNA ≤200 copies/ml was estimated every 24 weeks, using imputation if necessary to handle the different measurement schedule in Extended Follow-up; mean CD4 count changes were estimated using loess regression., Results and Discussion: Of 257 participants (38% females), at study entry, median CD4 count was 179 cells/mm 3 , and HIV-1 RNA was 4.6 log 10 copies/ml. Median follow-up was 168 weeks (IQR: 156-204); 15 (6%) participants were lost to follow-up and 9 (4%) died. 27/246 (11%), 26/246 (11%) and 13/92 (14%) of participants who started RAL, DRV/r and ETR, respectively, discontinued these drugs; only three due to adverse events. 87%, 86%, 83% and 80% of the participants had HIV-1 RNA ≤200 copies/ml at weeks 48, 96, 144 and 168 (95% CI at week 168: 74-85%), respectively. Mean increase from study entry in CD4 count at week 168 was 265 cells/mm 3 (95% CI 247-283)., Conclusions: Third-line regimens comprising of RAL, DRV/r and/or ETR were very well tolerated and had high rates of durable virologic suppression among PLWH in LMICs who were failing on second-line PI-based ART prior to the availability of dolutegravir., (© 2022 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

Background: Reducing congenital syphilis has been the focus of Brazilian health programs for decades, yet the cases continue to increase. Although health interventions have targeted HIV screening and treatment, syphilis management continues to be challenging. Syphilis during pregnancy may enhance the HIV maternal seroconversion risk. The potential factors fueling the syphilis epidemic were evaluated in south Brazil, an area of high HIV or syphilis endemicity., Objective: We hypothesized that ineffective treatment because of a lack of partner treatment, late presentation to care, and reinfection of previously treated mothers were potential drivers of syphilis mother-to-child transmission., Study Design: Data on women diagnosed with syphilis during pregnancy between January 1, 2008 and December 31, 2018 were obtained from a large urban hospital in Porto Alegre, Brazil. The patients were stratified into effective vs ineffective treatment groups according to the World Health Organization guidelines. Crude and adjusted risk ratios for the prediction of congenital syphilis and adverse fetal or neonatal outcomes were computed using Poisson regression., Results: Nearly 56,000 pregnant women delivered over the 11-year period; 1541 (2.8%) had confirmed syphilis during pregnancy, with 934 (61%) receiving ineffective syphilis treatment because of late presentation and diagnosis, delayed treatment initiation, and loss to follow-up with no treatment recorded. Ineffective treatment was associated with maternal education, prenatal care, timing of syphilis diagnosis, venereal diseases research laboratory titers, and maternal HIV coinfection. On multivariate regression analysis, ineffective treatment (adjusted risk ratio, 4.52; 95% confidence interval, 2.35-8.69), absence of prenatal care (adjusted risk ratio, 9.31; 95% confidence interval, 3.77-23.0), syphilis diagnosis at delivery (adjusted risk ratio, 3.08; 95% confidence interval, 2.07-4.58), and maternal nontreponemal titers ≥1:64 (1.09-1.93) were associated with an increased risk of fetal loss. Ineffective treatment (adjusted risk ratio, 1.71; 95% confidence interval, 1.59-1.84), year of diagnosis 2014 to 2016 (adjusted risk ratio, 1.07; 95% confidence interval, 1.02-1.13), absence of prenatal care (adjusted risk ratio, 1.44; 95% confidence interval, 1.17-1.76), and maternal nontreponemal titers >1:4 were associated with an increased risk of congenital syphilis. Although partner treatment reduced the congenital syphilis risk (adjusted risk ratio, 0.60; 95% confidence interval, 0.55-0.66), only 31.8% of partners received treatment. Maternal HIV coinfection was not associated with an increased risk of fetal loss, low birthweight, preterm birth, congenital syphilis, or symptomatic neonatal infection., Conclusion: Public health initiatives promoting effective syphilis treatment in pregnancy, increased access to high-quality prenatal care, and partner treatment should be considered to reduce congenital syphilis., Competing Interests: The authors report no conflict of interest.