Behavioral Assessment of Central Auditory Processing in Turner Syndrome.

Introduction Turner syndrome (TS) affects ∼ 1 in 2,500 live births. The presence of hearing alterations is one of the comorbidities found in this syndrome. Objective The present study aimed to evaluate the central auditory abilities in TS and to associate the alterations found with the cytogenetic pattern of the syndrome. Methods We included children and adults aged 9 to 39 years old, diagnosed with TS, with numerical or structural alterations of sex chromosomes in their karyotype. A battery of behavioral tests of central auditory processing (CAP) was performed, including a test within the modalities: monoaural low-redundancy, dichotic listening, binaural interaction, and temporal processing (resolution and ordering). We studied auditory skills in the total sample and in the sample stratified by age, divided into groups: G1 (9 to 13 years old), G2 (14 to 19 years old), and G3 (20 to 31 years old). For the association of the cytogenetic pattern, the division was T1 (chromosome monosomy X), and T2 (other TS cytogenetic patterns). Statistical analysis presented data expressed as median and interquartile range for numerical data and as frequency and percentage for categorical data. Results We found alterations in four auditory skills in the three age groups, but there was a statistically significant difference between the age groups only in the Gaps in Noise Test (GIN) ( p -value = 0.009). Regarding karyotype, a greater number of alterations in the T1 cytogenetic pattern (chromosome monosomy X) was observed in four auditory skills, but without a statistically significant difference. Conclusion The alterations found point to an impairment in CAP in TS.

Behavioral Assessment of Central Auditory Processing in Turner Syndrome

Abstract Introduction Turner syndrome (TS) affects ~ 1 in 2,500 live births. The presence of hearing alterations is one of the comorbidities found in this syndrome. Objective The present study aimed to evaluate the central auditory abilities in TS and to associate the alterations found with the cytogenetic pattern of the syndrome. Methods We included children and adults aged 9 to 39 years old, diagnosed with TS, with numerical or structural alterations of sex chromosomes in their karyotype. A battery of behavioral tests of central auditory processing (CAP) was performed, including a test within the modalities: monoaural low-redundancy, dichotic listening, binaural interaction, and temporal processing (resolution and ordering). We studied auditory skills in the total sample and in the sample stratified by age, divided into groups: G1 (9 to 13 years old), G2 (14 to 19 years old), and G3 (20 to 31 years old). For the association of the cytogenetic pattern, the division was T1 (chromosome monosomy X), and T2 (other TS cytogenetic patterns). Statistical analysis presented data expressed as median and interquartile range for numerical data and as frequency and percentage for categorical data. Results We found alterations in four auditory skills in the three age groups, but there was a statistically significant difference between the age groups only in the Gaps in Noise Test (GIN) (p-value = 0.009). Regarding karyotype, a greater number of alterations in the T1 cytogenetic pattern (chromosome monosomy X) was observed in four auditory skills, but without a statistically significant difference. Conclusion The alterations found point to an impairment in CAP in TS.

Does the Brazilian cash transfer program (bolsa familia): Protect nutritional deviations among infants and breastfeeding practices in a capital of the Central Region of Brazil?

Cash transfer programs are strategies used by countries, intended for impoverished families, which play an essential role in promoting access to public services such as health, education, and social protection. Programs may also promote food and nutrition security. The Brazilian Cash Transfer Program ("Bolsa Familia") (BFP) aims to alleviate immediate poverty and combat hunger. The aim of this study is to characterize the nutritional and breastfeeding status of children under two years old among both beneficiaries and non-beneficiaries of BFP. Data from the Brazilian Food and Nutritional Surveillance System, available in the primary healthcare service system of Goiania, Brazil, in 2013 were collected. The following variables were evaluated: sex, weight, height/length, age, and breastfeeding status. Data from 4,567 children under 24 months old were assessed, of which 2.72% (n= 124) were BFP beneficiaries. Beneficiaries had a lower odd of receiving breast milk compared to non-beneficiaries (OR= 0.46, 95% CI:0.31; 0.66, p= 0.0001). Regarding nutritional status, 18.14% (n= 790) of children were diagnosed with nutritional deviation, and overweight was the most prevalent (n=352, 8.04%). Beneficiaries presented a lower odd of developing stunting when compared to non-beneficiaries of BFP (OR= 0.44, 95% CI:0.25; 0.77, p= 0.006). Being a BFP beneficiary was a protective factor for the stunting in children under 24 months old in Goiania, Brazil. However, measures to promote and support breastfeeding should be intensified in primary healthcare service, aimed primarily at children in social vulnerability.

Los programas de transferencias en efectivo son estrategias utilizadas por los países, destinadas a familias en situación de pobreza y pobreza extrema, que juegan un papel fundamental en la promoción del acceso a los servicios públicos como salud, educación y protección social, además de promover la seguridad alimentaria y nutricional. El Programa Brasileño de Transferencias en Efectivo ("Bolsa Familia") (BFP) tiene como objetivo aliviar la pobreza inmediata y combatir el hambre. El objetivo de este estudio es caracterizar el estado nutricional y de lactancia de los niños menores de dos años, tanto beneficiarios como no beneficiarios del BFP. Se recogieron datos del Sistema de Vigilancia Alimentaria y Nutricional Brasileña, disponibles en el sistema de atención primaria de salud de Goiânia, Brasil, en 2013. Se evaluaron las siguientes variables, sexo, peso, talla, edad y estado de lactancia. Se evaluaron datos de 4.567 menores de 24 meses, de los cuales el 2.72% (n=124) eran beneficiarios del BFP. Las beneficiarias presentaron menos posibilidades de recibir leche materna en comparación con las no beneficiarias (OR= 0.46, IC95%:0,31; 0,66, p= 0,0001). En cuanto al estado nutricional, el 18,14% (n= 790) de los niños fueron diagnosticado con desviación nutricional, siendo el sobrepeso el más prevalente (n= 352, 8, 04%). Los beneficiarios presentaron menos probabilidad de desarrollar talla baja en comparación con los no beneficiarios del BFP (OR= 0.44, IC95%: 0.25; 0.77, p= 0.006). Ser beneficiario del BFP fue un factor de protección para la baja talla en menores de 24 meses en Goiania, Brasil. Sin embargo, se deben intensificar las medidas de promoción y apoyo a la lactancia materna en los servicios de atención primaria de salud, dirigidas principalmente a los niños en situación de vulnerabilidad social.

Single High Dose of Liposomal Amphotericin B in Human Immunodeficiency Virus/AIDS-Related Disseminated Histoplasmosis: A Randomized Trial.

BACKGROUND: Histoplasmosis is a major AIDS-defining illness in Latin America. Liposomal amphotericin B (L-AmB) is the drug of choice for treatment, but access is restricted due to the high drug and hospitalization costs of the conventional long regimens. METHODS: Prospective randomized multicenter open-label trial of 1- or 2-dose induction therapy with L-AmB versus control for disseminated histoplasmosis in AIDS, followed by oral itraconazole therapy. We randomized subjects to: (i) single dose 10 mg/kg of L-AmB; (ii) 10 mg/kg of L-AmB on D1, and 5 mg/kg of L-AmB on D3; (iii) 3 mg/kg of L-AmB daily for 2 weeks (control). The primary outcome was clinical response (resolution of fever and signs/symptoms attributable to histoplasmosis) at day 14. RESULTS: A total of 118 subjects were randomized, and median CD4+ counts, and clinical presentations were similar between arms. Infusion-related toxicity, kidney toxicity at multiple time-points, and frequency of anemia, hypokalemia, hypomagnesemia, and liver toxicity were similar. Day 14 clinical response was 84% for single-dose L-AmB, 69% 2-dose L-AmB, and 74% for control arm (P = .69). Overall survival on D14 was 89.0% (34/38) for single-dose L-AmB, 78.0% (29/37) for 2-dose L-AmB, and 92.1% (35/38) for control arm (P = .82). CONCLUSIONS: One day induction therapy with 10 mg/kg of L-AmB in AIDS-related histoplasmosis was safe. Although clinical response may be non-inferior to standard L-AmB therapy, a confirmatory phase III clinical trial is needed. A single induction dose would markedly reduce drug-acquisition costs (>4-fold) and markedly shorten and simplify treatment, which are key points in terms of increased access.

General Approach to Acute Myocardial Infarction with Nonobstructive Coronary Arteries (MINOCA): A Systematic Review

Abstract Background Acute myocardial infarction (AMI) without obstructive coronary arteries (MINOCA) is a medical condition of great relevance, with clinical characteristics of AMI, but without evidence of coronary artery obstruction. The mechanism involved in the pathophysiology of the disease and its possible etiologies are important objects of study due to their impact on the morbidity and mortality of affected patients. Objectives The aim of this study was to systematically review MINOCA and its characteristics, with emphasis on the clinical profile of patients, etiology, pathophysiology, diagnosis, and treatment of the syndrome. Methods Relevant articles related to MINOCA were analyzed in the PubMed and LILACS databases. In the initial search stage, 619 eligible articles were obtained, with final inclusion criteria being: original systematic reviews with clinical, epidemiological, diagnostic, or treatment data on MINOCA, published in Portuguese or English, with an abstract, and a publication date limit of September 2020. Results A total of 10 articles classified as systematic reviews that considered clinical data on MINOCA were included in this review. Conclusion After analyzing various literature, the present study provided a tool to better understand MINOCA, not only regarding its casuistry but also in grouping parameters and information that contribute to a healthy approach to this clinical situation. It was possible to identify and better outline the clinical profile of patients who presented this condition and the use of appropriate tools for correct diagnosis and ideal treatment.

Oligomeric α-Synuclein induces skin degeneration in reconstructed human epidermis.

Aged and photoaged skin exhibit fine wrinkles that are signs of epidermal inflammation and degeneration. It has been shown that healthy elderly skin expresses amyloidogenic proteins, including α-Synuclein, which are known to oligomerize and trigger inflammation and neurodegeneration. However, little is known about their putative role in skin physiology and sensitivity. To unravel this possible role, we investigated the impact of oligomeric α-Synuclein (Oα-Syn) in 2D and 3D keratinocyte human models. Exogenous Oα-Syn caused degeneration of reconstructed human epidermis (RHE) by diminishing proliferation and thickness of the stratum basale. Oα-Syn also increased NF-kB nuclear translocation in keratinocytes and triggered inflammation in the RHE, by increasing expression of interleukin-1ß and tumor necrosis factor-alpha, and the release of tumor necrosis factor-alpha in a time-dependent manner. Dexamethasone and an IL-1ß inhibitor partially diminished RHE degeneration caused by Oα-Syn. These findings suggest that Oα-Syn induces epidermal inflammation and decreases keratinocyte proliferation, and therefore might contribute to epidermal degeneration observed in human skin aging.

Efeito inibitório da via auditiva eferente na síndrome de Turner / Efferent Auditory Pathways Inhibition in Turner syndrome

RESUMO Objetivo investigar o efeito inibitório da via auditiva eferente na síndrome de Turner e relacionar com o perfil citogenético. Método estudo descritivo transversal com grupo de comparação. Amostra: Grupo estudo formado por 40 pacientes com síndrome de Turner (17,6 anos); e Grupo controle constituído por 54 indivíduos (18,9 anos), do sexo feminino sem síndrome. Os indivíduos selecionados foram submetidos à pesquisa do efeito inibitório da via auditiva eferente. Resultados A média do Efeito inibitório da via auditiva eferente no grupo estudo na orelha direita foi 0,4 dB e no grupo comparação foi de 1,9 dB, entretanto na orelha esquerda a média do efeito inibitório da via auditiva eferente foi 1,4 dB no grupo estudo e 0,8 dB no grupo comparação. O efeito inibitório da via auditiva eferente foi presente em 14 indivíduos com monossomia e em 15 com outras alterações citogenéticas. Conclusão No grupo estudo o valor do efeito inibitório da via auditiva eferente foi significantemente maior na orelha esquerda e significativamente menor que o grupo controle na direita. Não houve diferença significativa no efeito inibitório da via auditiva eferente entre os tipos de cariótipo.

ABSTRACT Purpose The goal of this study is to investigate the efferent auditory pathways inhibition in Turner's syndrome and to relate it to the cytogenetic profile. Methods This is a cross-sectional study with a comparison group. A sample with 94 participants divided into two groups: The study group was a sample of 40 patients diagnosed with Turner's syndrome (17.6 years of age). The control group was composed of 54 volunteers (18.9 years of age), female, without syndrome. The selected individuals were submitted to efferent auditory pathways inhibition research. Results The mean of the inhibitory effect of the efferent auditory pathway in the study group in the right ear was 0.4 dB and in the comparison group it was 1.9 dB, however in the left ear the mean of the inhibitory effect of the efferent auditory pathway was 1.4 dB in the study group and 0.8 dB in the comparison group. The inhibitory effect of the efferent auditory pathway was present in 14 individuals with monosomy and in 15 with other cytogenetic alterations. Conclusions In the study group, the efferent auditory pathways inhibition value was significantly higher in the left ear and significantly lower than the control group in the right ear. There was no significant difference in efferent auditory pathways inhibition of right ear and left ear between the karyotype types.

Efferent Auditory Pathways Inhibition in Turner syndrome. / Efeito inibitório da via auditiva eferente na síndrome de Turner.

PURPOSE: The goal of this study is to investigate the efferent auditory pathways inhibition in Turner's syndrome and to relate it to the cytogenetic profile. METHODS: This is a cross-sectional study with a comparison group. A sample with 94 participants divided into two groups: The study group was a sample of 40 patients diagnosed with Turner's syndrome (17.6 years of age). The control group was composed of 54 volunteers (18.9 years of age), female, without syndrome. The selected individuals were submitted to efferent auditory pathways inhibition research. RESULTS: The mean of the inhibitory effect of the efferent auditory pathway in the study group in the right ear was 0.4 dB and in the comparison group it was 1.9 dB, however in the left ear the mean of the inhibitory effect of the efferent auditory pathway was 1.4 dB in the study group and 0.8 dB in the comparison group. The inhibitory effect of the efferent auditory pathway was present in 14 individuals with monosomy and in 15 with other cytogenetic alterations. CONCLUSIONS: In the study group, the efferent auditory pathways inhibition value was significantly higher in the left ear and significantly lower than the control group in the right ear. There was no significant difference in efferent auditory pathways inhibition of right ear and left ear between the karyotype types.

OBJETIVO: investigar o efeito inibitório da via auditiva eferente na síndrome de Turner e relacionar com o perfil citogenético. MÉTODO: estudo descritivo transversal com grupo de comparação. Amostra: Grupo estudo formado por 40 pacientes com síndrome de Turner (17,6 anos); e Grupo controle constituído por 54 indivíduos (18,9 anos), do sexo feminino sem síndrome. Os indivíduos selecionados foram submetidos à pesquisa do efeito inibitório da via auditiva eferente. RESULTADOS: A média do Efeito inibitório da via auditiva eferente no grupo estudo na orelha direita foi 0,4 dB e no grupo comparação foi de 1,9 dB, entretanto na orelha esquerda a média do efeito inibitório da via auditiva eferente foi 1,4 dB no grupo estudo e 0,8 dB no grupo comparação. O efeito inibitório da via auditiva eferente foi presente em 14 indivíduos com monossomia e em 15 com outras alterações citogenéticas. CONCLUSÃO: No grupo estudo o valor do efeito inibitório da via auditiva eferente foi significantemente maior na orelha esquerda e significativamente menor que o grupo controle na direita. Não houve diferença significativa no efeito inibitório da via auditiva eferente entre os tipos de cariótipo.

Association between cytogenetic alteration and the audiometric profile of individuals with Turner syndrome / Relação entre alteração citogenética e o perfil audiométrico de indivíduos com síndrome de Turner

Abstract Introduction: Turner syndrome is a frequent genetic disorder that affects female individuals and covers a large phenotypic variability. Scientific literature suggests an association between hearing loss and Turner syndrome, but it remains a controversial topic. Objective: To associate the cytogenetic alteration with the audiometric profile of individuals with Turner syndrome. Methods: Cross-sectional study, with a hospital-based, convenience sample. Patients diagnosed with Turner syndrome were included and those with difficulty understanding the audiometry and/or other associated syndromes were excluded. The participants were studied with pure tone audiometry. Results: Of the 65 patients included, 36.9% had X chromosome monosomy and 63.0% had other alterations. Regarding the audiometry, 64.6% had normal thresholds and 35.3% had hearing impairment. Of these, 30.4% had hybrid hearing loss, 26.0% alteration at 6 and/or 8 kHz, 17.3% had conductive hearing loss, 13.0% sensorineural loss and 13.0% had mixed hearing loss. We observed that the mild degree was the most frequent one. There was no statistically significant association between the cytogenetic type of Turner syndrome and the presence or absence of hearing loss, or with the type and degree of hearing loss. Conclusion: The cytogenetic alteration in Turner syndrome was not associated with the audiometric profile, which showed variability regarding the type and degree of hearing loss.

Resumo Introdução: A síndrome de Turner é uma alteração frequente e genética que acomete indivíduos do sexo feminino e abrange grande variabilidade fenotípica. A literatura científica sugere uma relação entre perda auditiva e síndrome de Turner, porém ainda é um tema controverso. Objetivo: Relacionar a alteração citogenética com o perfil audiométrico de indivíduos com síndrome de Turner. Método: Estudo transversal, com amostra de conveniência, de base hospitalar. Foram incluídas pacientes com diagnóstico de síndrome de Turner e excluídas as com dificuldade para compreender a audiometria e/ou outras síndromes associadas. As participantes foram submetidas à audiometria tonal. Resultados: Das 65 pacientes incluídas, 36,9% apresentaram monossomia do cromossomo X e 63,0%, outras alterações. Com relação à audiometria, 64,6% apresentaram limiares dentro da normalidade e 35,3% alteração auditiva. Dessas, 30,4% apresentaram perda auditiva híbrida, 26,0% alteração em 6 e/ou 8 KHz; 17,3% perda auditiva condutiva, 13,0% perda neurossensorial e 13,0% perda auditiva mista. Observamos que o grau leve foi o mais frequente. Não foi observada associação estatiscamente significativa entre o tipo citogenético da síndrome de Turner e a presença ou não perda auditiva, ou com o tipo e grau de perda auditiva. Conclusão: A alteração citogenética na síndrome de Turner não teve associação com o perfil audiométrico, o qual apresentou variabilidade quanto ao tipo e grau da perda auditiva.

WIN 55,212-2 shows anti-inflammatory and survival properties in human iPSC-derived cardiomyocytes infected with SARS-CoV-2.

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which can infect several organs, especially impacting respiratory capacity. Among the extrapulmonary manifestations of COVID-19 is myocardial injury, which is associated with a high risk of mortality. Myocardial injury, caused directly or indirectly by SARS-CoV-2 infection, can be triggered by inflammatory processes that lead to damage to the heart tissue. Since one of the hallmarks of severe COVID-19 is the "cytokine storm", strategies to control inflammation caused by SARS-CoV-2 infection have been considered. Cannabinoids are known to have anti-inflammatory properties by negatively modulating the release of pro-inflammatory cytokines. Herein, we investigated the effects of the cannabinoid agonist WIN 55,212-2 (WIN) in human iPSC-derived cardiomyocytes (hiPSC-CMs) infected with SARS-CoV-2. WIN did not modify angiotensin-converting enzyme II protein levels, nor reduced viral infection and replication in hiPSC-CMs. On the other hand, WIN reduced the levels of interleukins six, eight, 18 and tumor necrosis factor-alpha (TNF-α) released by infected cells, and attenuated cytotoxic damage measured by the release of lactate dehydrogenase (LDH). Our findings suggest that cannabinoids should be further explored as a complementary therapeutic tool for reducing inflammation in COVID-19 patients.

Case Report: SARS-CoV-2 Mother-to-Child Transmission and Fetal Death Associated With Severe Placental Thromboembolism.

SARS-CoV-2 infection during pregnancy is not usually associated with significant adverse effects. However, in this study, we report a fetal death associated with mild COVID-19 in a 34-week-pregnant woman. The virus was detected in the placenta and in an unprecedented way in several fetal tissues. Placental abnormalities (MRI and anatomopathological study) were consistent with intense vascular malperfusion, probably the cause of fetal death. Lung histopathology also showed signs of inflammation, which could have been a contributory factor. Monitoring inflammatory response and coagulation in high-risk pregnant women with COVID-19 may prevent unfavorable outcomes, as shown in this case.

Non-permissive SARS-CoV-2 infection in human neurospheres.

Coronavirus disease 2019 (COVID-19) was initially described as a viral infection of the respiratory tract. It is now known, however, that several other organs are affected, including the brain. Neurological manifestations such as stroke, encephalitis, and psychiatric conditions have been reported in COVID-19 patients, but the neurotropic potential of the virus is still debated. Herein, we sought to investigate SARS-CoV-2 infection in human neural cells. We demonstrated that SARS-CoV-2 infection of neural tissue is non-permissive, however, it can elicit inflammatory response and cell damage. These findings add to the hypothesis that most of the neural damage caused by SARS-CoV-2 infection is due to a systemic inflammation leading to indirect harmful effects on the central nervous system despite the absence of local viral replication.

Body composition, but not insulin resistance, influences postprandial lipemia in patients with Turner's syndrome.

OBJECTIVE: The aim of the present study was to examine the influence of body composition and insulin resistance on the magnitude of postprandial lipemia in patients with Turner's syndrome receiving oral versus transdermal estrogen replacement. METHODS: Twenty-five patients with Turner's syndrome receiving oral or transdermal estrogen replacement were evaluated for body mass index, waist-to-hip and waist-to-height ratios, fasting glycemia, insulin, body composition (dual-energy X-ray absorptiometry), and postprandial lipid metabolism. For statistical analysis, we used parametric tests to compare numeric variables between the two subgroups. RESULTS: We observed no difference in postprandial triglyceride levels between patients receiving oral versus transdermal hormone replacement therapy. The postprandial triglycerides increment correlated positively with the percentage of total fat mass (p=0.02) and android fat mass (p=0.02) in the transdermal group. In the oral estrogen group, a positive correlation was observed between the increment in postprandial triglycerides and waist-to-hip (p=0.15) and waist-to-height (p=0.009) ratios. No association was observed between the estrogen replacement route and insulin resistance evaluated by the homeostatic model assessment-insulin resistance (HOMA-IR) index (p=0.19 and p=0.65 for the oral and transdermal groups, respectively). CONCLUSION: We concluded that body composition and anthropometric characteristics possibly affect the extent of postprandial lipemia independently from the route of estrogen replacement.

In vitro antiviral activity of the anti-HCV drugs daclatasvir and sofosbuvir against SARS-CoV-2, the aetiological agent of COVID-19.

BACKGROUND: Current approaches of drug repurposing against COVID-19 have not proven overwhelmingly successful and the SARS-CoV-2 pandemic continues to cause major global mortality. SARS-CoV-2 nsp12, its RNA polymerase, shares homology in the nucleotide uptake channel with the HCV orthologue enzyme NS5B. Besides, HCV enzyme NS5A has pleiotropic activities, such as RNA binding, that are shared with various SARS-CoV-2 proteins. Thus, anti-HCV NS5B and NS5A inhibitors, like sofosbuvir and daclatasvir, respectively, could be endowed with anti-SARS-CoV-2 activity. METHODS: SARS-CoV-2-infected Vero cells, HuH-7 cells, Calu-3 cells, neural stem cells and monocytes were used to investigate the effects of daclatasvir and sofosbuvir. In silico and cell-free based assays were performed with SARS-CoV-2 RNA and nsp12 to better comprehend the mechanism of inhibition of the investigated compounds. A physiologically based pharmacokinetic model was generated to estimate daclatasvir's dose and schedule to maximize the probability of success for COVID-19. RESULTS: Daclatasvir inhibited SARS-CoV-2 replication in Vero, HuH-7 and Calu-3 cells, with potencies of 0.8, 0.6 and 1.1 µM, respectively. Although less potent than daclatasvir, sofosbuvir alone and combined with daclatasvir inhibited replication in Calu-3 cells. Sofosbuvir and daclatasvir prevented virus-induced neuronal apoptosis and release of cytokine storm-related inflammatory mediators, respectively. Sofosbuvir inhibited RNA synthesis by chain termination and daclatasvir targeted the folding of secondary RNA structures in the SARS-CoV-2 genome. Concentrations required for partial daclatasvir in vitro activity are achieved in plasma at Cmax after administration of the approved dose to humans. CONCLUSIONS: Daclatasvir, alone or in combination with sofosbuvir, at higher doses than used against HCV, may be further fostered as an anti-COVID-19 therapy.

Quantitative profiling of axonal guidance proteins during the differentiation of human neurospheres.

Axon guidance is required for the establishment of brain circuits. Whether much of the molecular basis of axon guidance is known from animal models, the molecular machinery coordinating axon growth and pathfinding in humans remains to be elucidated. The use of induced pluripotent stem cells (iPSC) from human donors has revolutionized in vitro studies of the human brain. iPSC can be differentiated into neuronal stem cells which can be used to generate neural tissue-like cultures, known as neurospheres, that reproduce, in many aspects, the cell types and molecules present in the brain. Here, we analyzed quantitative changes in the proteome of neurospheres during differentiation. Relative quantification was performed at early time points during differentiation using iTRAQ-based labeling and LC-MS/MS analysis. We identified 6438 proteins, from which 433 were downregulated and 479 were upregulated during differentiation. We show that human neurospheres have a molecular profile that correlates to the fetal brain. During differentiation, upregulated pathways are related to neuronal development and differentiation, cell adhesion, and axonal guidance whereas cell proliferation pathways were downregulated. We developed a functional assay to check for neurite outgrowth in neurospheres and confirmed that neurite outgrowth potential is increased after 10 days of differentiation and is enhanced by increasing cyclic AMP levels. The proteins identified here represent a resource to monitor neurosphere differentiation and coupled to the neurite outgrowth assay can be used to functionally explore neurological disorders using human neurospheres as a model.

Association between cytogenetic alteration and the audiometric profile of individuals with Turner syndrome.

INTRODUCTION: Turner syndrome is a frequent genetic disorder that affects female individuals and covers a large phenotypic variability. Scientific literature suggests an association between hearing loss and Turner syndrome, but it remains a controversial topic. OBJECTIVE: To associate the cytogenetic alteration with the audiometric profile of individuals with Turner syndrome. METHODS: Cross-sectional study, with a hospital-based, convenience sample. Patients diagnosed with Turner syndrome were included and those with difficulty understanding the audiometry and/or other associated syndromes were excluded. The participants were studied with pure tone audiometry. RESULTS: Of the 65 patients included, 36.9% had X chromosome monosomy and 63.0% had other alterations. Regarding the audiometry, 64.6% had normal thresholds and 35.3% had hearing impairment. Of these, 30.4% had hybrid hearing loss, 26.0% alteration at 6 and/or 8kHz, 17.3% had conductive hearing loss, 13.0% sensorineural loss and 13.0% had mixed hearing loss. We observed that the mild degree was the most frequent one. There was no statistically significant association between the cytogenetic type of Turner syndrome and the presence or absence of hearing loss, or with the type and degree of hearing loss. CONCLUSION: The cytogenetic alteration in Turner syndrome was not associated with the audiometric profile, which showed variability regarding the type and degree of hearing loss.

Non-permissive SARS-CoV-2 infection in human neurospheres.

Coronavirus disease 2019 (COVID-19) was initially described as a viral infection of the respiratory tract. It is now known, however, that several other organs are affected, including the brain. Neurological manifestations such as stroke, encephalitis, and psychiatric conditions have been reported in COVID-19 patients, but the neurotropic potential of the virus is still debated. Herein, we sought to investigate SARS-CoV-2 infection in human neural cells. We demonstrated that SARS-CoV-2 infection of neural tissue is non-permissive, however, it can elicit inflammatory response and cell damage. These findings add to the hypothesis that most of the neural damage caused by SARS-CoV-2 infection is due to a systemic inflammation leading to indirect harmful effects on the central nervous system despite the absence of local viral replication.

Inhibition of SARS-CoV-2 infection in human iPSC-derived cardiomyocytes by targeting the Sigma-1 receptor disrupts cytoarchitecture and beating.

SARS-CoV-2 infects cardiac cells and causes heart dysfunction. Conditions such as myocarditis and arrhythmia have been reported in COVID-19 patients. The Sigma-1 receptor (S1R) is a ubiquitously expressed chaperone that plays a central role in cardiomyocyte function. S1R has been proposed as a therapeutic target because it may affect SARS-CoV-2 replication; however, the impact of the inhibition of S1R in human cardiomyocytes remains to be described. In this study, we investigated the consequences of S1R inhibition in iPSC-derived human cardiomyocytes (hiPSC-CM). SARS-CoV-2 infection in hiPSC-CM was productive and reduced cell survival. S1R inhibition decreased both the number of infected cells and viral particles after 48 hours. S1R inhibition also prevented the release of pro-inflammatory cytokines and cell death. Although the S1R antagonist NE-100 triggered those protective effects, it compromised cytoskeleton integrity by downregulating the expression of structural-related genes and reducing beating frequency. Our findings suggest that the detrimental effects of S1R inhibition in human cardiomyocytes' integrity may abrogate its therapeutic potential against COVID and should be carefully considered.