Premature ovarian insufficiency: knowledge, attitudes, and quality of care offered by gynecologists.

OBJECTIVE: Premature ovarian insufficiency (POI) affects up to 3% of the global female population, influencing metabolic, cardiovascular, and reproductive health. Medical expertise in diagnosis, effects, and treatment strategies, particularly for gynecologists, is crucial for ensuring improved healthcare for women. The objective of this study is to assess the state of medical knowledge regarding the diagnosis, treatment, and follow-up of POI among Brazilian gynecologists. METHODS: A cross-sectional study was conducted using online questionnaires administered to 16,000 members of the Brazilian Federation of Gynecology and Obstetrics. RESULTS: In total, 460 questionnaires were received from gynecologists who had an average age of 44.49 ± 12.57 years and 19.37 ± 12.95 years of professional experience. Fifty-three percent of gynecologists diagnosed POI correctly, and 49% requested karyotype analysis, while fewer than 10% identified all POI etiologies. Over 90% of gynecologists understood the long-term consequences of POI for bone and cardiovascular health. Despite being a consequence of hypoestrogenism, hormone therapy was recommended only by 20% of doctors, with no more than 50% of them prescribing appropriate doses for young women. Regarding self-perception, 60% of gynecologists declared deficient knowledge regarding how to offer care and guidance to women, with hormone therapy being reported as the most important reason (47%). CONCLUSIONS: Current concepts and guidelines for POI are not adequately understood or applied in Brazilian clinical practice, leading to suboptimal care.

Scissor-assisted vs. conventional endoscopic submucosal dissection for colorectal lesions: Systematic review and meta-analysis.

OBJECTIVES: Colorectal endoscopic submucosal dissection (ESD) is a technically complex procedure. The scissor knife mechanism may potentially provide easier and safer colorectal ESD. The aim of this meta-analysis is to evaluate the efficacy and safety of scissor-assisted vs. conventional ESD for colorectal lesions. METHODS: A search strategy was conducted in MEDLINE, Embase, and Lilacs databases from January 1990 to November 2023 according to PRISMA guidelines. Fixed and random-effects models were used for statistical analysis. Heterogeneity was assessed using I2 test. Risk of bias was assessed using the ROBINS-I and RoB-2 tools. Quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation tool. RESULTS: A total of five studies (three retrospective and two randomized controlled trials, including a total of 1575 colorectal ESD) were selected. The intraoperative perforation rate was statistically lower (risk difference [RD] -0.02; 95% confidence interval [CI] -0.04 to -0.01; P = 0.001; I2 = 0%) and the self-completion rate was statistically higher (RD 0.14; 95% CI 0.06, 0.23; P = 0.0006; I2 = 0%) in the scissor-assisted group compared with the conventional ESD group. There was no statistical difference in R0 resection rate, en bloc resection rate, mean procedure time, or delayed bleeding rate between the groups. CONCLUSION: Scissor knife-assisted ESD is as effective as conventional knife-assisted ESD for colorectal lesions with lower intraoperative perforation rate and a higher self-completion rate.

Rhodococcus erythropolis ATCC 4277 behavior against different metals and its potential use in waste biomining.

Rhodococcus erythropolis bacterium is known for its remarkable resistance characteristics that can be useful in several biotechnological processes, such as bioremediation. However, there is scarce knowledge concerning the behavior of this strain against different metals. This study sought to investigate the behavior of R. erythropolis ATCC 4277 against the residue of chalcopyrite and e-waste to verify both resistive capacities to the metals present in these residues and their potential use for biomining processes. These tests were carried out in a stirred tank bioreactor for 48 h, at 24ºC, pH 7.0, using a total volume of 2.0 L containing 2.5% (v/v) of a bacterial pre-culture. The pulp density of chalcopyrite was 5% (w/w), and agitation and oxygen flow rates were set to 250 rpm and 1.5 LO2 min-1, respectively. On the other hand, we utilized a waste of computer printed circuit board (WPCB) with a pulp density of 10% (w/w), agitation at 400 rpm, and an oxygen flow rate of 3.0 LO2 min-1. Metal concentration analyses post-fermentation showed that R. erythropolis ATCC 4277 was able to leach about 38% of the Cu present in the chalcopyrite residue (in ~ 24 h), and 49.5% of Fe, 42.3% of Ni, 27.4% of Al, and 15% Cu present in WPCB (in ~ 24 h). In addition, the strain survived well in the environment containing such metals, demonstrating the potential of using this bacterium for waste biomining processes as well as in other processes with these metals.

Functional and Effective Connectivity Underlying Semantic Verbal Fluency.

Semantic verbal fluency (SVF) impairment is present in several neurological disorders. Although activation in SVF-related areas has been reported, how these regions are connected and their functional roles in the network remain divergent. We assessed SVF static and dynamic functional connectivity (FC) and effective connectivity in healthy participants using functional magnetic resonance imaging. We observed activation in the inferior frontal (IFG), middle temporal (pMTG) and angular gyri (AG), anterior cingulate (AC), insular cortex, and regions of the superior, middle, and medial frontal gyri (SFG, MFG, MidFG). Our static FC analysis showed a highly interconnected task and resting state network. Increased connectivity of AC with the pMTG and AG was observed for the task. The dynamic FC analysis provided circuits with connections similarly modulated across time and regions related to category identification, language comprehension, word selection and recovery, word generation, inhibition of speaking, speech planning, and articulatory planning of orofacial movements. Finally, the effective connectivity analysis provided a network that best explained our data, starting at the AG and going to the pMTG, from which there was a division between the ventral and dorsal streams. The SFG and MFG regions were connected and modulated by the MidFG, while the inferior regions formed the ventral stream. Therefore, we successfully assessed the SVF network, exploring regions associated with the entire processing, from category identification to word generation. The methodological approach can be helpful for further investigation of the SVF network in neurological disorders.

The Effect of Thiazide Diuretics on Urinary Prostaglandin E2 Excretion and Serum Sodium in the General Population.

CONTEXT: Thiazide-induced hyponatremia is one of the most common forms of hyponatremia, but its pathogenesis is incompletely understood. Recent clinical data suggest links with prostaglandin E2 (PGE2) and a single nucleotide polymorphism (SNP) in the prostaglandin transporter gene (SLCO2A1), but it is unknown if these findings also apply to the general population. OBJECTIVE: To study the associations between serum sodium, thiazide diuretics, urinary excretions of PGE2 and its metabolite (PGEM), and the rs34550074 SNP in SLCO2A1 in the general population. DESIGN: Prospective population-based cohort study (Rotterdam Study). SETTING: General population. PARTICIPANTS: 2,178 participants (65% female, age 64 ± 8 years). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Serum sodium levels. RESULTS: Higher urinary PGE2 excretion was associated with lower serum sodium: difference in serum sodium for each two-fold higher PGE2 -0.19 mmol/l (95%CI -0.31 to -0.06), PGEM -0.29 mmol/l (95%CI -0.41 to -0.17). This association was stronger in thiazide users (per two-fold higher PGE2 -0.73 vs. -0.12 mmol/l and PGEM -0.6 vs. -0.25 mmol/l, p for interaction < 0.05 for both). A propensity score matching analysis of thiazide vs. non-thiazide users yielded similar results. The SNP rs34550074 was not associated with lower serum sodium or higher urinary PGE2 or PGEM excretion in thiazide or non-thiazide users. CONCLUSIONS: Serum sodium is lower in people with higher urinary PGE2 and PGEM excretion and this association is stronger in thiazide users. This suggests that PGE2-mediated water reabsorption regulates serum sodium, which is relevant for the pathogenesis of hyponatremia in general and thiazide-induced hyponatremia in specific.

Calcineurin inhibitor effects on kidney electrolyte handling and blood pressure: tacrolimus versus voclosporin.

BACKGROUND AND HYPOTHESIS: Calcineurin inhibitors affect kidney electrolyte handling and blood pressure through an effect on the distal tubule. The second generation calcineurin inhibitor voclosporin causes hypomagnesemia and hypercalciuria less often than tacrolimus. This suggests different effects on the distal tubule, but this has not yet been investigated experimentally. METHODS: Rats were treated with voclosporin, tacrolimus or vehicle for 28 days. Dosing was based on a pilot experiment to achieve clinically therapeutic concentrations. Drug effects were assessed by electrolyte handling at day 18 and 28, thiazide testing at day 20, telemetric blood pressure recordings, and analysis of mRNA and protein levels of distal tubular transporters at day 28. RESULTS: Compared to vehicle, tacrolimus but not voclosporin significantly increased the fractional excretions of calcium (>4-fold), magnesium and chloride (both 1.5-fold) and caused hypomagnesemia. Tacrolimus but not voclosporin significantly reduced distal tubular transporters at mRNA and/or protein level, including the sodium-chloride cotransporter, transient receptor melastatin 6, transient receptor potential vanilloid 5, cyclin M2, sodium-calcium exchanger and calbindin-D28K. Tacrolimus but not voclosporin reduced the mRNA level and urinary excretion of epidermal growth factor. The saluretic response to hydrochlorothiazide at day 20 was similar in the voclosporin and vehicle groups, whereas it was lower in the tacrolimus group. The phosphorylated form of the sodium-chloride cotransporter was significantly higher at day 28 in rats treated with voclosporin than in those treated with tacrolimus. Tacrolimus transiently increased blood pressure, whereas voclosporin caused a gradual but persistent increase in blood pressure which was further characterized by high renin, normal aldosterone, and low endothelin-1. CONCLUSIONS: In contrast to tacrolimus, voclosporin does not cause hypercalciuria and hypomagnesemia, but similarly causes hypertension. Our data reveal differences between the distal tubular effects of tacrolimus and voclosporin and provide a pathophysiological basis for the clinically observed differences between the two calcineurin inhibitors.

Neurocognition and brain functional connectivity in a non-clinical population-based sample with psychotic experiences.

We characterized the neurocognitive profile of communed-based individuals and unaffected siblings of patients with psychosis from Brazil reporting psychotic experiences (PEs). We also analyzed associations between PEs and the intra and inter-functional connectivity (FC) in the Default Mode Network (DMN), the Fronto-Parietal Network (FPN) and the Salience Network (SN) measured by functional magnetic resonance imaging. The combined sample of communed-based individuals and unaffected siblings of patients with psychosis comprised 417 (neurocognition) and 85 (FC) volunteers who were divided as having low (<75th percentile) and high (≥75th percentile) PEs (positive, negative, and depressive dimensions) assessed by the Community Assessment of Psychic Experiences. The neurocognitive profile and the estimated current brief intellectual quotient (IQ) were assessed using the digit symbol (processing speed), arithmetic (working memory), block design (visual learning) and information (verbal learning) subtests of Wechsler Adult Intelligence Scale-third edition. Logistic regression models were performed for neurocognitive analysis. For neuroimaging, we used the CONN toolbox to assess FC between the specified regions, and ROI-to-ROI analysis. In the combined sample, high PEs (all dimensions) were related to lower processing speed performance. High negative PEs were related to poor visual learning performance and lower IQ, while high depressive PEs were associated with poor working memory performance. Those with high negative PEs presented FPN hypoconnectivity between the right and left lateral prefrontal cortex. There were no associations between PEs and the DMN and SN FC. Brazilian individuals with high PEs showed neurocognitive impairments like those living in wealthier countries. Hypoconnectivity in the FPN in a community sample with high PEs is coherent with the hypothesis of functional dysconnectivity in schizophrenia.

Designing, development and validation of an app to reduce the response time of the emergency medical services.

INTRODUCTION: Delays in prehospital care attributable to the call-taking process can often be traced back to miscommunication, including uncertainty around the call location. Geolocation applications have the potential to streamline the call-taking process by accurately identifying the caller's location. OBJECTIVE: To develop and validate an application to geolocate emergency calls and compare the response time of calls made via the application with those of conventional calls made to the Brazilian Medical Emergency System (Serviço de Atendimento Médico de Urgência-SAMU). METHODS: This study was conducted in two stages. First, a geolocating application for SAMU emergency calls (CHAMU192) was developed using a mixed methods approach based on design thinking and subsequently validated using the System Usability Scale (SUS). In the second stage, sending time of the geolocation information of the app was compared with the time taken to process information through conventional calls. For this, a hypothetical case control study was conducted with SAMU in the Maringá, Paraná, Brazil. A control group of 350 audio recordings of emergency calls from 2019 was compared to a set of test calls made through the CHAMU192 app. The CHAMU192 group consisted of 201 test calls in Maringá. In test calls, the location was obtained by GPS and sent to the SAMU communication system. Comparative analysis between groups was performed using the Mann-Whitney test. RESULTS: CHAMU192 had a SUS score of 90, corresponding to a "best imaginable" usability rating. The control group had a median response time of 35.67 seconds (26.00-48.12). The response time of the CHAMU192 group was 0.20 (0.15-0.24). CONCLUSION: The use of the CHAMU192 app by emergency medical services could significantly reduce response time. The results demonstrate the potential of app improving the quality and patient outcomes related to the prehospital emergency care services.

Post-discharge all-cause mortality in COVID-19 recovered patients hospitalized in 2020: the impact of chronic kidney disease.

In Brazil, the COVID-19 burden was substantial, and risk factors associated with higher in-hospital mortality rates have been extensively studied. However, information on short-term all-cause mortality and the factors associated with death in patients who survived the hospitalization period of acute SARS-CoV-2 infection is limited. We analyzed the six-month post-hospitalization mortality rate and possible risk factors of COVID-19 patients in a single center in Brazil. This is a retrospective cohort study focused on a six-month follow-up. The exclusion criteria were death during hospitalization, transference to another hospital, and age under 18. We collected data from the charts of all hospitalized patients from March 2020 to December 2020 with a positive RT-PCR test for SARS-CoV-2, resulting in a sample size of 106 patients. The main outcome was death after hospitalization, whereas comorbidities and demographics were evaluated as risk factors. The crude post-hospitalization death rate was 16%. The first 30 days of follow-up had the highest mortality rate. In a Cox regression model for post-hospitalization mortality, previous chronic kidney disease (HR, 4.06, 95%CI 1.46 - 11.30) and longer hospital stay (HR 1.01, 95%CI 1.00 - 1.02) were the only factors statistically associated with death. In conclusion, a high six-month all-cause mortality was observed. Within the six-month follow-up, a higher risk of death was observed for patients who had prior CKD and longer hospital stay. These findings highlight the importance of more intensive medical surveillance during this period.

Serum sclerostin is associated with recurrent kidney stone formation independent of hypercalciuria.

Background: Kidney stones are frequent in industrialized countries with a lifetime risk of 10 to 15%. A high percentage of individuals experience recurrence. Calcium-containing stones account for more than 80% of kidney stones. Diet, environmental factors, behavior, and genetic variants contribute to the development of kidney stones. Osteocytes excrete the 21 kDa glycoprotein sclerostin, which inhibits bone formation by osteoblasts. Animal data suggests that sclerostin might directly or indirectly regulate calcium excretion via the kidney. As hypercalciuria is one of the most relevant risk factors for kidney stones, sclerostin might possess pathogenic relevance in nephrolithiasis. Methods: We performed a prospective cross-sectional observational controlled study in 150 recurrent kidney stone formers (rKSF) to analyse the association of sclerostin with known stone risk factors and important modulators of calcium-phosphate metabolism. Serum sclerostin levels were determined at the first visit. As controls, we used 388 non-stone formers from a large Swiss epidemiological cohort. Results: Sclerostin was mildly increased in rKSF in comparison to controls. This finding was more pronounced in women compared to men. Logistic regression indicated an association of serum sclerostin with rKSF status. In hypercalciuric individuals, sclerostin levels were not different from normocalciuric patients. In Spearman correlation analysis we found a positive correlation between sclerostin, age, and BMI and a negative correlation with eGFR. There was a weak correlation with iPTH and intact FGF 23. In contrast, serum sclerostin levels were not associated with 25-OH Vitamin D3, 1,25-dihydroxy-Vitamin D3, urinary calcium and phosphate or other urinary lithogenic risk factors. Conclusion: This is the first prospective controlled study investigating serum sclerostin in rKSF. Sclerostin levels were increased in rKSF independent of hypercalciuria and significantly associated with the status as rKSF. It appears that mechanisms other than hypercalciuria may be involved and thus further studies are required to elucidate underlying pathways.

Post-discharge all-cause mortality in COVID-19 recovered patients hospitalized in 2020: the impact of chronic kidney disease

ABSTRACT In Brazil, the COVID-19 burden was substantial, and risk factors associated with higher in-hospital mortality rates have been extensively studied. However, information on short-term all-cause mortality and the factors associated with death in patients who survived the hospitalization period of acute SARS-CoV-2 infection is limited. We analyzed the six-month post-hospitalization mortality rate and possible risk factors of COVID-19 patients in a single center in Brazil. This is a retrospective cohort study focused on a six-month follow-up. The exclusion criteria were death during hospitalization, transference to another hospital, and age under 18. We collected data from the charts of all hospitalized patients from March 2020 to December 2020 with a positive RT-PCR test for SARS-CoV-2, resulting in a sample size of 106 patients. The main outcome was death after hospitalization, whereas comorbidities and demographics were evaluated as risk factors. The crude post-hospitalization death rate was 16%. The first 30 days of follow-up had the highest mortality rate. In a Cox regression model for post-hospitalization mortality, previous chronic kidney disease (HR, 4.06, 95%CI 1.46 - 11.30) and longer hospital stay (HR 1.01, 95%CI 1.00 - 1.02) were the only factors statistically associated with death. In conclusion, a high six-month all-cause mortality was observed. Within the six-month follow-up, a higher risk of death was observed for patients who had prior CKD and longer hospital stay. These findings highlight the importance of more intensive medical surveillance during this period.

Centros de Atenção Psicossocial e formação profissional para oferta das Práticas Integrativas e Complementares: estudo com profissionais ofertantes dos serviços / Psychosocial care centers and professional training for the provision of integrative and complementary practices: a study with professionals offering these services / Centros de Atención Psicosocial y formación profesional para oferta de las Prácticas Integradoras y Complementarias: estudio con profesionales ofertantes de los servicios

Estudos sobre a formação em Práticas Integrativas e Complementares têm se concentrado na análise curricular dos cursos da Saúde e as pesquisas abrangendo as percepções dos profissionais a respeito dos processos formativos devem ser mais elucidadas. O estudo objetiva identificar os processos de formação e capacitação dos profissionais ofertantes de Práticas Integrativas e Complementares nos Centros de Atenção Psicossocial de uma região metropolitana. Trata-se de um estudo descritivo, exploratório, de abordagem qualitativa. Realizaram-se entrevistas semiestruturadas com 45 profissionais, as quais foram posteriormente analisadas segundo a Análise de Conteúdo Temática. As pós-graduações, graduação, formações em serviço e o ensino privado foram as trajetórias adotadas pelos profissionais, revelando a existência de uma formação difusa para a oferta no cenário investigado. Esses resultados podem subsidiar o planejamento de estratégias educacionais para a ordenação dos recursos humanos em Práticas Integrativas e Complementares.

Studies of training in integrative and complementary practices have concentrated on the analysis of the curriculums of health courses and further more in-depth research into professionals' perceptions about training processes is needed. This study aimed to identify training processes and capacity building for professionals who offer integrative and complementary practices in psychosocial care centers in a metropolitan region. We conducted an exploratory descriptive study involving semi-structured interviews with 45 professionals. The interview transcripts were analyzed using content analysis. The most common routes taken by the professionals were post-graduate qualifications, degrees, in-service training and private education. The results reveal that training in this area was diffuse. Our results can inform the development of educational strategies for the organization of human resources in the area of integrative and complementary practices.

Los estudios sobre la formación en Prácticas Integradoras y Complementarias se han concentrado en el análisis curricular de los cursos de la salud y las investigaciones que incluyen las percepciones de los profesionales con relación a los procesos de formación deben elucidarse más. El objetivo del estudio es identificar los procesos de formación y capacitación de los profesionales ofertantes de Prácticas Integradoras y Complementarias en los Centros de Atención Psicosocial de una región metropolitana. Se trata de un estudio descriptivo, exploratorio, de abordaje cualitativo. Se realizaron entrevistas semiestructuradas con 45 profesionales que fueron posteriormente analizadas según el Análisis de Contenido Temático. Los postgrados, graduación, formaciones en servicio y la enseñanza privada fueron las trayectorias adoptadas por los profesionales, revelando la existencia de una formación difusa para la oferta en el escenario investigado. Esos resultados pueden subsidiar la planificación de estrategias educativas para la ordenación de los recursos humanos en las Prácticas Integradoras y Complementarias.

An electric field modeling study with meta-analysis to understand the antidepressant effects of transcranial direct current stimulation (tDCS)

Objective: Transcranial direct current stimulation (tDCS) has mixed effects for major depressive disorder (MDD) symptoms, partially owing to large inter-experimental variability in tDCS protocols and their correlated induced electric fields (E-fields). We investigated whether the E-field strength of distinct tDCS parameters was associated with antidepressant effect. Methods: A meta-analysis was performed with placebo-controlled clinical trials of tDCS enrolling MDD patients. PubMed, EMBASE, and Web of Science were searched from inception to March 10, 2023. Effect sizes of tDCS protocols were correlated with E-field simulations (SimNIBS) of brain regions of interest (bilateral dorsolateral prefrontal cortex [DLPFC] and bilateral subgenual anterior cingulate cortex [sgACC]). Moderators of tDCS responses were also investigated. Results: A total of 20 studies were included (21 datasets, 1,008 patients), using 11 distinct tDCS protocols. Results revealed a moderate effect for MDD (g = 0.41, 95%CI 0.18-0.64), while cathode position and treatment strategy were found to be moderators of response. A negative association between effect size and tDCS-induced E-field magnitude was seen, with stronger E-fields in the right frontal and medial parts of the DLPFC (targeted by the cathode) leading to smaller effects. No association was found for the left DLPFC and the bilateral sgACC. An optimized tDCS protocol is proposed. Conclusions: Our results highlight the need for a standardized tDCS protocol in MDD clinical trials. Registration number: PROSPERO CRD42022296246.

Magnetic Waves vs. Electric Shocks: A Non-Inferiority Study of Magnetic Seizure Therapy and Electroconvulsive Therapy in Treatment-Resistant Depression.

Treatment-resistant depression (TRD), characterized by the failure to achieve symptomatic remission despite multiple pharmacotherapeutic treatments, poses a significant challenge for clinicians. Electroconvulsive therapy (ECT) is an effective but limited option due to its cognitive side effects. In this context, magnetic seizure therapy (MST) has emerged as a promising alternative, offering comparable antidepressant efficacy with better cognitive outcomes. However, the clinical outcomes and cognitive effects of MST require further investigation. This double-blinded, randomized, non-inferiority study aims to compare the efficacy, tolerability, cognitive adverse effects, and neurophysiological biomarkers of MST with bilateral ECT (BT ECT) in patients with TRD. This study will employ multimodal nuclear magnetic resonance imaging (MRI) and serum neurotrophic markers to gain insight into the neurobiological basis of seizure therapy. Additionally, neurophysiological biomarkers will be evaluated as secondary outcomes to predict the antidepressant and cognitive effects of both techniques. The study design, recruitment methods, ethical considerations, eligibility criteria, interventions, and blinding procedures are described. The expected outcomes will advance the field by offering a potential alternative to ECT with improved cognitive outcomes and a better understanding of the underlying pathophysiology of depression and antidepressant therapies.

MicroRNAs Associated with the Pathophysiological Mechanisms of Gestational Diabetes Mellitus: A Systematic Review for Building a Panel of miRNAs.

miRNAs, a class of small non-coding RNAs, play a role in post-transcriptional gene expression. Therefore, this study aimed to conduct a systematic review of miRNAs associated with GDM to build a panel of miRNAs. A bibliographic search was carried out in the PubMed/Medline, Virtual Health Library (VHL), Web of Science, and EMBASE databases, selecting observational studies in English without time restriction. The protocol was registered on the PROSPERO platform (number CRD42021291791). Fifty-five studies were included in this systematic review, and 82 altered miRNAs in GDM were identified. In addition, four miRNAs were most frequently dysregulated in GDM (mir-16-5p, mir-20a-5p, mir-222-3p, and mir-330-3p). The dysregulation of these miRNAs is associated with the mechanisms of cell cycle homeostasis, growth, and proliferation of pancreatic ß cells, glucose uptake and metabolism, insulin secretion, and resistance. On the other hand, identifying miRNAs associated with GDM and elucidating its main mechanisms can assist in the characterization and definition of potential biomarkers for the diagnosis and treatment of GDM.

Ovarian cancer G protein-coupled receptor 1 deficiency exacerbates crystal deposition and kidney injury in oxalate nephropathy in female mice.

Ovarian cancer G protein-coupled receptor 1 (OGR1) (Gpr68) and G protein-coupled receptor 4 (GPR4) (Gpr4) are proton-activated G protein-coupled receptors that are stimulated upon increased extracellular acidity. These receptors have various physiological and pathophysiological roles in renal acid-base physiology, tissue inflammation, and fibrosis among others. Their function in injured renal tissue, however, remains mostly unclear. To address this, we investigated their role in crystalline nephropathy by increasing the oxalate intake of GPR4 KO and OGR1 KO mice. After 10 days of high-oxalate intake and 4 days of recovery, renal crystal content, histopathology, filtration function, and inflammation were assessed. While GPR4 deficiency did not show major alterations in disease progression, OGR1 KO mice had higher urinary calcium levels and exacerbated crystal accumulation accompanied by decreased creatinine clearance and urea excretion and a decreased presence of regulatory T (Treg) cells in kidney tissue. When lowering the severity of the kidney injury, OGR1 KO mice were more prone to develop crystalline nephropathy. In this setting, OGR1 KO mice displayed an increased activation of the immune system and a higher production of proinflammatory cytokines by T cells and macrophages. Taken together, in the acute setting of oxalate-induced nephropathy, the lack of the proton-activated G protein-coupled receptor (GPCR) GPR4 does not influence disease. OGR1 deficiency, however, increases crystal deposition leading to impaired kidney function. Thus, OGR1 may be important to limit kidney crystal deposition, which might subsequently be relevant for the pathophysiology of oxalate kidney stones or other crystallopathies.

CBIR-SAR System Using Stochastic Distance.

This article proposes a system for Content-Based Image Retrieval (CBIR) using stochastic distance for Synthetic-Aperture Radar (SAR) images. The methodology consists of three essential steps for image retrieval. First, it estimates the roughness (α^) and scale (γ^) parameters of the GI0 distribution that models SAR data in intensity. The parameters of the model were estimated using the Maximum Likelihood Estimation and the fast approach of the Log-Cumulants method. Second, using the triangular distance, CBIR-SAR evaluates the similarity between a query image and images in the database. The stochastic distance can identify the most similar regions according to the image features, which are the estimated parameters of the data model. Third, the performance of our proposal was evaluated by applying the Mean Average Precision (MAP) measure and considering clippings from three radar sensors, i.e., UAVSAR, OrbiSaR-2, and ALOS PALSAR. The CBIR-SAR results for synthetic images achieved the highest MAP value, retrieving extremely heterogeneous regions. Regarding the real SAR images, CBIR-SAR achieved MAP values above 0.833 for all polarization channels for image samples of forest (UAVSAR) and urban areas (ORBISAR). Our results confirmed that the proposed method is sensitive to the degree of texture, and hence, it relies on good estimates. They are inputs to the stochastic distance for effective image retrieval.

An electric field modeling study with meta-analysis to understand the antidepressant effects of transcranial direct current stimulation (tDCS).

OBJECTIVE: Transcranial direct current stimulation (tDCS) has mixed effects for major depressive disorder (MDD) symptoms, partially owing to large inter-experimental variability in tDCS protocols and their correlated induced electric fields (E-fields). We investigated whether the E-field strength of distinct tDCS parameters was associated with antidepressant effect. METHODS: A meta-analysis was performed with placebo-controlled clinical trials of tDCS enrolling MDD patients. PubMed, EMBASE, and Web of Science were searched from inception to March 10, 2023. Effect sizes of tDCS protocols were correlated with E-field simulations (SimNIBS) of brain regions of interest (bilateral dorsolateral prefrontal cortex [DLPFC] and bilateral subgenual anterior cingulate cortex [sgACC]). Moderators of tDCS responses were also investigated. RESULTS: A total of 20 studies were included (21 datasets, 1,008 patients), using 11 distinct tDCS protocols. Results revealed a moderate effect for MDD (g = 0.41, 95%CI 0.18-0.64), while cathode position and treatment strategy were found to be moderators of response. A negative association between effect size and tDCS-induced E-field magnitude was seen, with stronger E-fields in the right frontal and medial parts of the DLPFC (targeted by the cathode) leading to smaller effects. No association was found for the left DLPFC and the bilateral sgACC. An optimized tDCS protocol is proposed. CONCLUSION: Our results highlight the need for a standardized tDCS protocol in MDD clinical trials.

Self-made transvaginal ultrasound simulator: new training equipment in ultrasound evaluation of controlled ovarian stimulation and oocyte retrieval.

Aim: We sought to create and describe a self-made simulator designed and created for teaching purposes: a high-fidelity ultrasound phantom for demonstrating antral follicle count, ultrasound supervision of controlled of ovarian stimulation, and ultrasound-guided oocyte retrieval. Materials and methods: The uterus and ovaries of the ultrasound phantom were made from beef tongue, a male condom, latex gloves, cotton suture threads, bi-distilled water, and ultrasound gel. The components were placed in a pelvis created using three-dimensional (3D) printing. The phantom was presented to and evaluated by a group of 14 physicians pursuing a postgraduate course in reproductive medicine. Two training stations were structured: one to simulate antral follicle count and controlled ovarian stimulation and the other to simulate ultrasound-guided oocyte retrieval. Future specialists were requested to complete a feedback questionnaire evaluating the self-made simulator and the two practice stations. Results: The transvaginal ultrasound phantom was successfully created, making it possible to simulate antral follicle count, ultrasound control of ovarian hyperstimulation, and oocyte retrieval, and to capture ultrasound images. A review of the answers provided in the feedback questionnaire showed that the phantom had a good appearance and design, was realistic, helped to improve motor coordination, and could be a useful tool in the training of specialists in assisted reproduction. Conclusion: This phantom was designed to enable instruction and practice in the evaluation of ovarian follicles and ultrasound-guided oocyte retrieval in a supervised training environment. This self-made simulator is proposed as a training tool that could be included in the curricular structure of residency and postgraduate programs in reproductive medicine.

The use of immunotherapies for recurrent miscarriage: An overview of systematic reviews and meta-analysis.

Immunotherapies have been a treatment proposed for recurrent miscarriages (RMs). The use of immunotherapies remains not recommended in the management of couples with RM. This overview of systematic reviews and meta-analysis (SRs-MAs) aims to identify and evaluate the quality of SRs-MAs that studied the effectiveness of immunotherapies in the treatment of RM patients. SRs-MAs were searched in PubMed/Medline, Embase, and Web of Science. SRs-MAs were analyzed using AMSTAR-2, PRISMA 2020, Risk of Bias in Systematic (ROBIS), and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tools to evaluate the methodological quality, reporting quality, risk of bias, and evidence quality of included SRs-MAs, respectively. This review included 20 SRs-MAs that evaluated the following immunotherapies: intravenous immunoglobulin (13 publications), lymphocyte immunotherapy (6 publications), corticosteroids (3 publications), and lipid emulsion (1 publication). SRs-MAs were rated as high methodological, moderate, and critically low quality in 14 (70 %), 1 (5 %), and 5 (25 %) SRs-MAs and high reporting, moderate, and low quality in 13 (65 %), 4 (20 %), and 3 (5 %) SRs-MAs, respectively. The overall risk of bias revealed a low risk of bias for three-quarters of the SRs-MAs. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) analysis resulted in 23 outcomes, of which 4, 3, 5, and 11 results were of high, moderate, low, and very low quality, respectively. An improvement has been observed over the past few years in the quality of systematic reviews (SR)-MAs that have investigated the efficacy of intravenous immunoglobulin, lymphocyte immunotherapy, lipid emulsion therapy, and corticosteroids as a therapy for RM.