Trio-based whole exome sequencing in patients with ectopic posterior pituitary.

Introduction: Ectopic posterior pituitary (EPP) is a rare congenital abnormality, sometimes associated with other midline defects, such as pituitary stalk interruption syndrome (PSIS), in which thin or absent pituitary stalk and anterior pituitary hypoplasia are combined to EPP. Most cases are sporadic, with few reports of familial cases, and many congenital hypopituitarism (CH) cases remain unsolved. Objective: To search for candidate genes associated with this condition, we performed trio-based whole-exome sequencing (WES) on patients with EPP, including two familial cases. Methods: This study included subjects with EPP and PSIS diagnosed by a simple MRI protocol (FAST1.2). We performed two distinct analyses in the trio-based WES. We looked for previously described genes associated with pituitary development. Next, we investigated the whole exome for variants inherited in a pattern consistent with a monogenic etiology. Results: Ten families were evaluated; eight were composed of a child with EPP and healthy parents, one has two affected siblings, and one family has a son and mother with EPP. When analyzing the previously described candidate variants associated with pituitary development, we found variants in GLI2 and FGFR1 in three families. We also found six other variants of interest in three patients: KMT2A, GALR3, RTN4R, SEMA3A, NIPBL, and DSCAML1. Conclusion: The analysis allowed us to find previously reported and not reported GLI2 variants, all inherited from healthy parents, which reinforces the incomplete penetrance pattern of GLI2 variants in the development of EPP and draws attention to possible future functional studies of those variants that have a recurrent expression in CH. We also found novel FGFR1 and SEMA3A variants that suggest an oligogenic mechanism in PSIS and EPP, as seen in patients with hypogonadotropic hypogonadism. We report the first case of a patient with Wiedemann-Steiner syndrome and PSIS, suggesting that the KMT2A gene may be related to pituitary development. Furthermore, the trios' analysis allowed us to find five other variants of interest. Future investigations may clarify the roles of these variants in the etiology of EPP and PSIS.

High-resolution mapping of urban Aedes aegypti immature abundance through breeding site detection based on satellite and street view imagery.

Identification of Aedes aegypti breeding hotspots is essential for the implementation of targeted vector control strategies and thus the prevention of several mosquito-borne diseases worldwide. Training computer vision models on satellite and street view imagery in the municipality of Rio de Janeiro, we analyzed the correlation between the density of common breeding grounds and Aedes aegypti infestation measured by ovitraps on a monthly basis between 2019 and 2022. Our findings emphasized the significance (p ≤ 0.05) of micro-habitat proxies generated through object detection, allowing to explain high spatial variance in urban abundance of Aedes aegypti immatures. Water tanks, non-mounted car tires, plastic bags, potted plants, and storm drains positively correlated with Aedes aegypti egg and larva counts considering a 1000 m mosquito flight range buffer around 2700 ovitrap locations, while dumpsters, small trash bins, and large trash bins exhibited a negative association. This complementary application of satellite and street view imagery opens the pathway for high-resolution interpolation of entomological surveillance data and has the potential to optimize vector control strategies. Consequently it supports the mitigation of emerging infectious diseases transmitted by Aedes aegypti, such as dengue, chikungunya, and Zika, which cause thousands of deaths each year.

Sperm-borne miR-34c-5p and miR-191-3p as markers for sperm motility and embryo developmental competence.

BACKGROUND: Sperm-borne microRNAs play a pivotal role in influencing essential cellular processes during fertilization, impacting the quality of embryo development. Dysregulated microRNA profiles have been associated with compromised embryonic development and increased incidences of pregnancy loss. OBJECTIVE: This study aimed to investigate the potential associations between the abundance of miR-34c-5p and miR-191-3p in human spermatozoa with sperm quality, as well as with embryo quality and metabolic performance during in vitro development. MATERIALS AND METHODS: Thirteen couples who underwent a total of 13 cycles participated in this study. The sperm quality was assessed using conventional methods following World Health Organization guidelines. Quantitative polymerase chain reaction was employed to measure microRNA abundance in spermatozoa. Embryos were categorized as good, lagging, or bad based on morphokinetic evaluation. Evaluation of embryo metabolic performance involved tracking changes in specific metabolites within the cultured media using nuclear magnetic resonance spectroscopy. Statistical analysis was conducted to explore the correlation between microRNA abundance in human spermatozoa and all other collected data. RESULTS: Our findings revealed a negative correlation between the abundance of miR-34c-5p (but not miR-191-3p) and total sperm motility, potentially mediated by the modulation of key signaling pathways. Additionally, higher levels of miR-34c-5p in spermatozoa were strongly associated with the consumption or release of key metabolites by developing embryos, particularly those linked with lipid and glucose metabolism, suggesting enhanced metabolic performance, while miR-191-3p was mostly associated with glucose consumption. Concurrently, only miR-34c-5p content in spermatozoa correlated with higher embryo quality. DISCUSSION AND CONCLUSION: This study provides evidence suggesting that the abundance of miR-34c-5p in spermatozoa is correlated not only with total sperm motility but also with markers of embryo developmental competence, highlighting the potential significance of this sperm microRNA content as a biomarker in assisted reproduction.

The new era of artificial intelligence in neuroradiology: current research and promising tools.

Radiology has a number of characteristics that make it an especially suitable medical discipline for early artificial intelligence (AI) adoption. These include having a well-established digital workflow, standardized protocols for image storage, and numerous well-defined interpretive activities. The more than 200 commercial radiologic AI-based products recently approved by the Food and Drug Administration (FDA) to assist radiologists in a number of narrow image-analysis tasks such as image enhancement, workflow triage, and quantification, corroborate this observation. However, in order to leverage AI to boost efficacy and efficiency, and to overcome substantial obstacles to widespread successful clinical use of these products, radiologists should become familiarized with the emerging applications in their particular areas of expertise. In light of this, in this article we survey the existing literature on the application of AI-based techniques in neuroradiology, focusing on conditions such as vascular diseases, epilepsy, and demyelinating and neurodegenerative conditions. We also introduce some of the algorithms behind the applications, briefly discuss a few of the challenges of generalization in the use of AI models in neuroradiology, and skate over the most relevant commercially available solutions adopted in clinical practice. If well designed, AI algorithms have the potential to radically improve radiology, strengthening image analysis, enhancing the value of quantitative imaging techniques, and mitigating diagnostic errors.

A radiologia tem uma série de características que a torna uma disciplina médica especialmente adequada à adoção precoce da inteligência artificial (IA), incluindo um fluxo de trabalho digital bem estabelecido, protocolos padronizados para armazenamento de imagens e inúmeras atividades interpretativas bem definidas. Tal adequação é corroborada pelos mais de 200 produtos radiológicos comerciais baseados em IA recentemente aprovados pelo Food and Drug Administration (FDA) para auxiliar os radiologistas em uma série de tarefas restritas de análise de imagens, como quantificação, triagem de fluxo de trabalho e aprimoramento da qualidade das imagens. Entretanto, para o aumento da eficácia e eficiência da IA, além de uma utilização clínica bem-sucedida dos produtos que utilizam essa tecnologia, os radiologistas devem estar atualizados com as aplicações em suas áreas específicas de atuação. Assim, neste artigo, pesquisamos na literatura existente aplicações baseadas em IA em neurorradiologia, mais especificamente em condições como doenças vasculares, epilepsia, condições desmielinizantes e neurodegenerativas. Também abordamos os principais algoritmos por trás de tais aplicações, discutimos alguns dos desafios na generalização no uso desses modelos e introduzimos as soluções comercialmente disponíveis mais relevantes adotadas na prática clínica. Se cautelosamente desenvolvidos, os algoritmos de IA têm o potencial de melhorar radicalmente a radiologia, aperfeiçoando a análise de imagens, aumentando o valor das técnicas de imagem quantitativas e mitigando erros de diagnóstico.

Bacterial diversity in semen from stallions in three European countries evaluated by 16S sequencing.

The microbiome plays a significant role in shaping the health and functioning of the systems it inhabits. The seminal microbiome of stallions has implications for the health of the reproductive tract, sperm quality during preservation and antibiotic use in semen extenders. Diverse bacteria are present on the external genital tract and a mix of commensal microorganisms populates various parts of the reproductive tract, influencing the seminal bacterial content. Other sources of bacteria include the environment, semen collection equipment, and personnel. The bacterial load can adversely affect sperm quality and fertility, particularly in artificial insemination, where semen is extended and stored before use. Antibiotics are frequently used to inhibit bacterial growth, but their effectiveness varies depending on the bacterial strains present. The aim of this study was to assess the bacterial diversity in semen from 37 healthy stallions across three European nations (Germany, Portugal, and Sweden) using 16S sequencing. Semen samples were collected from individual stallions at three AI centers; DNA extraction, sequencing, and bioinformatic analysis were performed. Differences in bacterial diversity among the stallions were seen; although bacterial phyla were shared across the regions, differences were observed at the genus level. Climate, husbandry practices, and individual variability likely contribute to these differences. These findings underscore the importance of tailoring antibiotic strategies for semen preservation based on regional bacterial profiles. The study presents a comprehensive approach to understanding the intricacies of the stallion seminal microbiome and its potential implications for reproductive technologies and animal health.

The new era of artificial intelligence in neuroradiology: current research and promising tools / A nova era da inteligência artificial em neurorradiologia: pesquisa atual e ferramentas promissoras

Abstract Radiology has a number of characteristics that make it an especially suitable medical discipline for early artificial intelligence (AI) adoption. These include having a well-established digital workflow, standardized protocols for image storage, and numerous well-defined interpretive activities. The more than 200 commercial radiologic AI-based products recently approved by the Food and Drug Administration (FDA) to assist radiologists in a number of narrow image-analysis tasks such as image enhancement, workflow triage, and quantification, corroborate this observation. However, in order to leverage AI to boost efficacy and efficiency, and to overcome substantial obstacles to widespread successful clinical use of these products, radiologists should become familiarized with the emerging applications in their particular areas of expertise. In light of this, in this article we survey the existing literature on the application of AI-based techniques in neuroradiology, focusing on conditions such as vascular diseases, epilepsy, and demyelinating and neurodegenerative conditions. We also introduce some of the algorithms behind the applications, briefly discuss a few of the challenges of generalization in the use of AI models in neuroradiology, and skate over the most relevant commercially available solutions adopted in clinical practice. If well designed, AI algorithms have the potential to radically improve radiology, strengthening image analysis, enhancing the value of quantitative imaging techniques, and mitigating diagnostic errors.

Resumo A radiologia tem uma série de características que a torna uma disciplina médica especialmente adequada à adoção precoce da inteligência artificial (IA), incluindo um fluxo de trabalho digital bem estabelecido, protocolos padronizados para armazenamento de imagens e inúmeras atividades interpretativas bem definidas. Tal adequação é corroborada pelos mais de 200 produtos radiológicos comerciais baseados em IA recentemente aprovados pelo Food and Drug Administration (FDA) para auxiliar os radiologistas em uma série de tarefas restritas de análise de imagens, como quantificação, triagem de fluxo de trabalho e aprimoramento da qualidade das imagens. Entretanto, para o aumento da eficácia e eficiência da IA, além de uma utilização clínica bem-sucedida dos produtos que utilizam essa tecnologia, os radiologistas devem estar atualizados com as aplicações em suas áreas específicas de atuação. Assim, neste artigo, pesquisamos na literatura existente aplicações baseadas em IA em neurorradiologia, mais especificamente em condições como doenças vasculares, epilepsia, condições desmielinizantes e neurodegenerativas. Também abordamos os principais algoritmos por trás de tais aplicações, discutimos alguns dos desafios na generalização no uso desses modelos e introduzimos as soluções comercialmente disponíveis mais relevantes adotadas na prática clínica. Se cautelosamente desenvolvidos, os algoritmos de IA têm o potencial de melhorar radicalmente a radiologia, aperfeiçoando a análise de imagens, aumentando o valor das técnicas de imagem quantitativas e mitigando erros de diagnóstico.

Metabolomics Integration in Assisted Reproductive Technologies for Enhanced Embryo Selection beyond Morphokinetic Analysis.

Embryo quality evaluation during in vitro development is a crucial factor for the success of assisted reproductive technologies (ARTs). However, the subjectivity inherent in the morphological evaluation by embryologists can introduce inconsistencies that impact the optimal embryo choice for transfer. To provide a more comprehensive evaluation of embryo quality, we undertook the integration of embryo metabolomics alongside standardized morphokinetic classification. The culture medium of 55 embryos (derived from 21 couples undergoing ICSI) was collected at two timepoints (days 3 and 5). Samples were split into Good (n = 29), Lagging (n = 19), and Bad (n = 10) according to embryo morphokinetic evaluation. Embryo metabolic performance was assessed by monitoring the variation in specific metabolites (pyruvate, lactate, alanine, glutamine, acetate, formate) using 1H-NMR. Adjusted metabolite differentials were observed during the first 3 days of culture and found to be discriminative of embryo quality at the end of day 5. Pyruvate, alanine, glutamine, and acetate were major contributors to this discrimination. Good and Lagging embryos were found to export and accumulate pyruvate and glutamine in the first 3 days of culture, while Bad embryos consumed them. This suggests that Bad embryos have less active metabolic activity than Good and Lagging embryos, and these two metabolites are putative biomarkers for embryo quality. This study provides a more comprehensive evaluation of embryo quality and can lead to improvements in ARTs by enabling the selection of the best embryos. By combining morphological assessment and metabolomics, the selection of high-quality embryos with the potential to result in successful pregnancies may become more accurate and consistent.

Chronic Coronary Syndrome: Medical Therapy or Myocardial Revascularization?

Abstract The best therapeutic strategy for chronic coronary syndrome (CCS) is still controversial. The lack of contemporaneity of medical treatment in many randomized clinical trials prior to the large-scale use of statins, antiplatelet agents, anti-diabetic drugs with cardiovascular protection, and changes in life habits with well-established goals limits the applicability of such studies in current clinical practice. Medical treatment is the only therapeutic option capable of reducing atherosclerotic damage and, therefore, of acting effectively in preventing the progression of this disease. The purpose of this brief review is to critically analyze the main contemporary studies that confront medical treatment with myocardial revascularization in CCS.

Extra-pituitary midline structural abnormalities associated with ectopic posterior pituitary detected on a new rapid MRI protocol (FAST1.2)

ABSTRACT Objective: Test if the MRI FAST1.2 protocol can detect extra-pituitary midline structural brain abnormalities in patients with ectopic posterior pituitary (EPP), and highlighting their radiological-laboratory correlations. Subjects and methods: Cross-sectional study of patients with EPP and control group. All individuals were submitted to FAST1.2, which combines the FAST1 protocol developed by our group with 3D T2DRIVE imaging. Results: We evaluated 36 individuals with EPP and 78 as control group. Pituitary stalk (PS) was identified in 7/36 patients in EPP group by FAST1, and in 24/36 patients in FAST1.2 (p < 0.001). FAST1 failed to detect PS in one individual in the control group, while the FAST1.2 defined the PS in all individuals. In EPP group, eleven had interhypothalamic adhesion (IHA), three septo-optic dysplasia, and one cerebellar malformation. We didn't observe higher frequency of panhypopituitarism or developmental delay in patients with IHA. In control group, three had pars intermedia cysts, one hydrocephalus, and one hypothalamic hamartoma. Conclusions: FAST1.2 allows confident recognition of midline structural abnormalities, including the pituitary stalk and IHA, thereby making MRI acquisition faster and with no need for contrast administration. IHA could be associated with defects in neuronal migration, as occur in patients with EPP, with no clinical significance.

Neurological imaging findings in hospitalized COVID-19 patients: a retrospective observational study in two Brazilian reference centers / Achados de neuroimagem em pacientes hospitalizados por COVID-19: um estudo retrospectivo e observacional em dois serviços brasileiros de referência

ABSTRACT Background: A variety of neurological manifestations have been attributed to COVID-19. Objective: To investigate the occurrence of neurological symptoms and neuroimaging findings in patients hospitalized in two Brazilian reference centers. Methods: We performed a retrospective cohort study of patients who had laboratory-confirmed COVID-19 presenting in two hospitals in Brazil between March 4 and July 7, 2020, who underwent brain imaging. Results: We recorded 1,359 patients with laboratory-confirmed COVID-19. Brain imaging was performed in 250 (18.4%) patients with neurological symptoms, and nine of them (3.6%) had acute or subacute ischemic stroke neuroimaging findings. Six of the nine patients initially presented with respiratory symptoms while the other three patients presented to the emergency room with acute stroke signs. Conclusions: We described the neuroimaging findings of patients infected with COVID-19 who presented with neurological symptoms in two major hospitals in Brazil. We reinforce the importance of being aware of cerebrovascular complications, both in severe hospitalized patients and in patients who present to the emergency room with acute neurological symptoms, even in the elderly.

RESUMO Introdução: Diversas manifestações neurológicas têm sido atribuídas à COVID-19. Objetivo: Investigar a ocorrência de sintomas neurológicos e achados de neuroimagem em pacientes internados em dois centros de referência brasileiros. Métodos: Estudo retrospectivo que avaliou pacientes internados em dois hospitais no Brasil entre 4 de março e 7 de julho de 2020, com confirmação laboratorial de infecção pelo COVID-19 e que foram submetidos a tomografia computadorizada ou ressonância magnética do crânio em razão de sintomas neurológicos. Resultados: Obtivemos 1.359 pacientes com confirmação laboratorial de infecção pelo COVID-19. Deles, 250 (18,4%) apresentaram sintomas neurológicos e foram submetidos a exames de imagem do crânio e nove (3,6%) demonstraram achados de neuroimagem compatíveis com acidente vascular cerebral (AVC) isquêmico agudo ou subagudo. Em seis dos nove pacientes, observaram-se inicialmente tosse e dispneia graves, enquanto outros três chegaram ao pronto-socorro com sinais de AVC agudo. Conclusões: Foram descritos os achados de neuroimagem em pacientes infectados com COVID-19 em dois grandes centros de referência brasileiros. Reforçamos a importância de estar atento aos quadros neurológicos, especialmente de AVC, tanto em pacientes graves hospitalizados quanto em pacientes que chegam ao pronto-socorro com sintomas neurológicos agudos, mesmo em idosos.

Predictive Value of Myocardial injury in Patients with COVID-19 Admitted to a Quaternary Hospital in the City of Rio de Janeiro

Abstract Background In Brazil the factors involved in the risk of death in patients with COVID-19 have not been well established. Objective To analyze whether elevations of high-sensitivity troponin I (hTnI) levels influence the mortality of patients with COVID-19. Methods Clinical and laboratory characteristics of hospitalized patients with COVID-19 were collected upon hospital admission. Univariate and binary logistic regression analyzes were performed to assess the factors that influence mortality. P-value<0.05 was considered significant. Results This study analyzed192 patients who received hospital admission between March 16 and June 2, 2020 and who were discharged or died by July 2, 2020. The mean age was 70±15 years, 80 (41.7%) of whom were women. In comparison to those who were discharged, the 54 (28.1%) who died were older (79±12 vs 66±15years; P=0.004), and with a higher Charlson´s index (5±2 vs 3±2; P=0.027). More patients, aged≥60years (P <0.0001), Charlson´s index>1 (P=0.004), lung injury>50% in chest computed tomography (P=0.011), with previous coronary artery disease (P=0.037), hypertension (P=0.033), stroke (P=0.008), heart failure (P=0.002), lymphocytopenia (P=0.024), high D-dimer (P=0.024), high INR (P=0.003), hTnI (P<0.0001), high creatinine (P<0.0001), invasive mechanical ventilation (P<0.0001), renal replacement therapy (P<0.0001), vasoactive amine (P<0.0001), and transfer to the ICU (P=0.001), died when compared to those who were discharged. In logistic regression analysis, elevated hTnI levels (OR=9.504; 95% CI=1.281-70.528; P=0.028) upon admission, and the need for mechanical ventilation during hospitalization (OR=46.691; 95% CI=2.360-923.706; P=0.012) increased the chance of in-hospital mortality. Conclusion This study suggests that in COVID-19 disease, myocardial injury upon hospital admission is a harbinger of poor prognosis.

Current uses of intracranial vessel wall imaging for clinical practice: a high-resolution MR technique recently available / Usos atuais do estudo de parede vascular intracraniana na prática clínica: uma técnica de RM de alta resolução recentemente disponível

ABSTRACT Intracranial vessel wall imaging plays an increasing role in diagnosing intracranial vascular diseases. With the growing demand and subsequent increased use of this technique in clinical practice, radiologists and neurologists should be aware of the choices in imaging parameters and how they affect image quality, clinical indications, methods of assessment, and limitations in the interpretation of these images. Due to the improvement of the MRI techniques, the possibility of accurate and direct evaluation of the abnormalities in the arterial vascular wall (vessel wall imaging) has evolved, adding substantial data to diagnosis when compared to the indirect evaluation based on conventional flow analyses. Herein, the authors proposed a comprehensive approach of this technique reinforcing appropriated clinical settings to better use intracranial vessel wall imaging.

RESUMO O estudo angiográfico intracraniano não invasivo está sendo amplamente utilizado no diagnóstico de doenças vasculares intracranianas. Com a crescente demanda e o aumento subsequente do uso dessa técnica na prática clínica, radiologistas e neurologistas devem estar cientes das opções nos parâmetros de imagem e como estes afetam a qualidade da imagem, as indicações clínicas, os métodos de avaliação e as limitações na interpretação dessas imagens. Devido ao aprimoramento das técnicas de imagem por RM, a possibilidade de avaliação precisa e direta das anormalidades na parede vascular arterial (vessel wall imaging) evoluiu, agregando dados substanciais ao diagnóstico quando comparados à avaliação indireta baseada em análises de fluxo convencionais. Neste artigo, os autores discorrem sobre a avaliação e interpretação dos achados de imagem desta nova técnica e suas aplicações clínicas.