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With the development of in vitro technologies, embryos can be produced using oocytes retrieved directly from the ovaries, i.e., regardless of ovulation. This has allowed the use of different animal categories as oocyte donors, including prepubertal cattle. The advantages of using this strategy to shorten the generation interval and accelerate genetic gain over time were soon recognized, and the first offspring generated using oocytes collected from calves were born in the early 1990s. Nevertheless, embryo production from calves and prepubertal heifers remains a challenge. The oocytes collected before puberty present low in vitro developmental potential, and the subsequent blastocyst rates are consistently lower than those from pubertal females. The acquisition of developmental competence by the oocytes occurs progressively throughout the prepubertal period, which can be subdivided into an early, intermediate, and late prepubertal (or peripubertal) phases, each characterized by different physiological and endocrine features. Therefore, embryo yield increases with age but will only achieve its maximum after puberty. The most common strategy to improve oocyte developmental potential before puberty is the use of gonadotrophic stimulation prior to oocyte retrieval. The results with superstimulation, however, vary among studies, depending on the source, dose, and length of FSH treatment, as well as the age and breed of the donors. The use of calves and prepubertal heifers as oocyte donors should also consider the possible impacts of the oocyte retrieval technique (LOPU or OPU) and the use of exogenous hormones on their subsequent fertility and productive life.
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The aim of this study was to evaluate the superestimulatory and superovulatory responses of cattle treated with corifollitropin-alpha, a long-acting human recombinant FSH (rhFSH). In the first and second experiments, we used Nelore (Bos indicus) heifers previously submitted to follicular wave suppression by active immunization against GnRH. In Experiment 1 (a dose-response study), heifers (n = 20) were randomly allocated into five groups, which received placebo (saline) or a single sc dose of 7.5, 15.0, 22.5 or 30.0 µg rhFSH. The heifers were subjected to daily ovarian scan and blood sampling during 11 days. We observed group, time, and group x time effects (P<0.0001) for both average follicle size and circulating FSH concentrations, with a strong correlation (R = 0.82, P<0.0001) between the area under curve (AUC) for both parameters. The peak concentration of FSH 24h after treatment and average follicle size at all timepoints, however, were similar (P>0.05) between groups 22.5 and 30.0 µg. In Experiment 2, heifers (n = 18) were allocated into three groups, which received (0h) either placebo (control), 25 µg rhFSH or 130 mg pFSH (Folltropin). There was no difference (P>0.05) in average follicle size at any moment, as well as in intrafollicular E2 at 120h or in plasma P4 seven days later between groups rhFSH and pFSH. In Experiment 3, cycling Nelore heifers (n = 20) were subjected to a wave synchronization protocol and superovulated (day 0) using a standard pFSH protocol (120 mg split in eight decreasing im doses) or with a single sc injection of 20 µg rhFSH. The number of follicles >7 mm on day 4 did not differ (P=0.4370). Heifers receiving rhFSH had greater average follicle size on day 4 (P=0.0005), ovulation rate (P<0.0001), and number of CL (P=0.0155), as well as a trend towards a greater number of ova (P=0.07) and viable embryos (P=0.0590). In Experiment 4, superovulation was induced with a single sc injection of 25 µg rhFSH in Girolando and Nelore cows and heifers (n = 20). None of the embryo yield endpoints differed between the two breeds (P>0.05). In conclusion, cattle superstimulation and superovulation can be successfully induced with a single dose of a long-acting rhFSH (corifollitropin-alpha).
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Relação Dose-Resposta a Droga , Hormônio Foliculoestimulante Humano , Ovário , Superovulação , Bovinos , Animais , Feminino , Superovulação/efeitos dos fármacos , Hormônio Foliculoestimulante Humano/administração & dosagem , Hormônio Foliculoestimulante Humano/farmacologia , Ovário/efeitos dos fármacos , Meia-Vida , Gravidez , Hormônio Foliculoestimulante/farmacologia , Hormônio Foliculoestimulante/administração & dosagem , Folículo Ovariano/efeitos dos fármacos , Proteínas Recombinantes/farmacologia , Proteínas Recombinantes/administração & dosagem , HumanosRESUMO
BACKGROUND: Adopting advanced digital technologies as diagnostic support tools in healthcare is an unquestionable trend accelerated by the COVID-19 pandemic. However, their accuracy in suggesting diagnoses remains controversial and needs to be explored. We aimed to evaluate and compare the diagnostic accuracy of two free accessible internet search tools: Google and ChatGPT 3.5. METHODS: To assess the effectiveness of both medical platforms, we conducted evaluations using a sample of 60 clinical cases related to urological pathologies. We organized the urological cases into two distinct categories for our analysis: (i) prevalent conditions, which were compiled using the most common symptoms, as outlined by EAU and UpToDate guidelines, and (ii) unusual disorders, identified through case reports published in the 'Urology Case Reports' journal from 2022 to 2023. The outcomes were meticulously classified into three categories to determine the accuracy of each platform: "correct diagnosis", "likely differential diagnosis", and "incorrect diagnosis". A group of experts evaluated the responses blindly and randomly. RESULTS: For commonly encountered urological conditions, Google's accuracy was 53.3%, with an additional 23.3% of its results falling within a plausible range of differential diagnoses, and the remaining outcomes were incorrect. ChatGPT 3.5 outperformed Google with an accuracy of 86.6%, provided a likely differential diagnosis in 13.3% of cases, and made no unsuitable diagnosis. In evaluating unusual disorders, Google failed to deliver any correct diagnoses but proposed a likely differential diagnosis in 20% of cases. ChatGPT 3.5 identified the proper diagnosis in 16.6% of rare cases and offered a reasonable differential diagnosis in half of the cases. CONCLUSION: ChatGPT 3.5 demonstrated higher diagnostic accuracy than Google in both contexts. The platform showed satisfactory accuracy when diagnosing common cases, yet its performance in identifying rare conditions remains limited.
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Ferramenta de Busca , Humanos , COVID-19/diagnóstico , Internet , Doenças Urológicas/diagnóstico , SARS-CoV-2 , Diagnóstico DiferencialRESUMO
Delayed initiation of effective antifibrotic therapy in patients with interstitial lung diseases (ILD) may influence the progression and outcome of the disease. This study analyzes the differences in the journey of patients with ILD in the Brazilian and Mexican health systems. An evaluative study was conducted in reference centers for interstitial lung diseases in Brazil and Mexico with a panel of four specialists. The patient's journey in both countries begins when the patient seeks medical care after observing a chronic respiratory symptom. In both countries, due to diagnostic complexity, these patients arrive at ILD referral centers at an advanced stage of the disease. Once diagnosis is established, the treatment onset differs between Mexico and Brazil. In Brazil, access to antifibrotic drugs through the public health system has been a significant challenge, and their cost makes them unaffordable for most people. This situation forces medical specialists to provide only supportive care to patients until these drugs can be accessed. In Mexico, antifibrotics have been available in health sectors since 2018. Brazil and Mexico have several similarities regarding the initial journey of the patient due to diagnosis difficulties. Still, the outcome tends to be different due to a difference in access to treatment with antifibrotics. For this reason, advancing health policies that ensure proper treatment for patients with ILD is crucial for the sustainability and reliability of the health system.
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Diagnóstico Precoce , Acessibilidade aos Serviços de Saúde , Doenças Pulmonares Intersticiais , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/terapia , Doenças Pulmonares Intersticiais/tratamento farmacológico , Humanos , Brasil , MéxicoRESUMO
Blood-brain barrier (BBB) models derived from human stem cells are powerful tools to improve our understanding of cerebrovascular diseases and to facilitate drug development for the human brain. Yet providing stem cell-derived endothelial cells with the right signaling cues to acquire BBB characteristics while also retaining their vascular identity remains challenging. Here, we show that the simultaneous activation of cyclic AMP and Wnt/ß-catenin signaling and inhibition of the TGF-ß pathway in endothelial cells robustly induce BBB properties in vitro. To target this interaction, we present a small-molecule cocktail named cARLA, which synergistically enhances barrier tightness in a range of BBB models across species. Mechanistically, we reveal that the three pathways converge on Wnt/ß-catenin signaling to mediate the effect of cARLA via the tight junction protein claudin-5. We demonstrate that cARLA shifts the gene expressional profile of human stem cell-derived endothelial cells toward the in vivo brain endothelial signature, with a higher glycocalyx density and efflux pump activity, lower rates of endocytosis, and a characteristic endothelial response to proinflammatory cytokines. Finally, we illustrate how cARLA can improve the predictive value of human BBB models regarding the brain penetration of drugs and targeted nanoparticles. Due to its synergistic effect, high reproducibility, and ease of use, cARLA has the potential to advance drug development for the human brain by improving BBB models across laboratories.
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Barreira Hematoencefálica , Células Endoteliais , Barreira Hematoencefálica/metabolismo , Humanos , Células Endoteliais/metabolismo , Animais , Via de Sinalização Wnt , Claudina-5/metabolismo , Claudina-5/genética , AMP Cíclico/metabolismo , Camundongos , Células-Tronco/metabolismo , Células-Tronco/citologia , Junções Íntimas/metabolismo , beta Catenina/metabolismoRESUMO
BACKGROUND: The worst outcomes linked to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been attributed to the cytokine storm, which contributes significantly to the immunopathogenesis of the disease. The mammalian target of rapamycin (mTOR) pathway is essential for orchestrating innate immune cell defense including cytokine production and is dysregulated in severe Coronavirus Disease 2019 (COVID-19) individuals. The individual genetic background might play a role in the exacerbated immune response. OBJECTIVE: In this study, we aimed to investigate the association between MTOR genetic variants and COVID-19 outcomes. METHODS: This study enrolled groups of individuals with severe (n = 285) and mild (n = 207) COVID-19 from Brazilian states. The MTOR variants, rs1057079 and rs2536, were genotyped. A logistic regression analysis and Kaplan-Meier survival curves were performed. We applied a genotyping risk score to estimate the cumulative contribution of the risk alleles. Tumor necrosis factor (TNF) and interleukin-6 (IL-6) plasma levels were also measured. RESULTS: The T allele of the MTOR rs1057079 variant was associated with a higher likelihood of developing the most severe form of COVID-19. In addition, higher levels of IL-6 and COVID-19 death was linked to the T allele of the rs2536 variant. These variants exhibited a cumulative risk when inherited collectively. CONCLUSIONS: These results show a potential pathogenetic role of MTOR gene variants and may be useful for predicting severe outcomes following COVID-19 infection, resulting in a more effective allocation of health resources.
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COVID-19 , Variação Genética , Serina-Treonina Quinases TOR , Humanos , COVID-19/genética , COVID-19/imunologia , COVID-19/mortalidade , COVID-19/patologia , Gravidade do Paciente , Estudos de Casos e Controles , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Análise de Sobrevida , Citocinas/sangue , Serina-Treonina Quinases TOR/genéticaRESUMO
Introduction: The aim of this study was to evaluate potential effects of diflubenzuron on the production and quality of gametes, and on in vitro embryo production (IVEP) outcomes, in cattle. Methods: Two experiments were performed, the first to evaluate effects on semen, and the second on cumulus-oocyte complexes (COC) and on IVEP. Nelore (Bos taurus indicus) bulls (n = 14) or heifers (n = 16) were allocated into control (CG) or treatment (DIF) groups. All groups received a mineral mix supplement added (DIF) or not (CG) with diflubenzuron (30 mg/head/day), during 8 weeks. Animals were weighed and blood samples were collected throughout the experimental period. Every other week, bulls were subjected to semen collection and heifers to transvaginal ultrasound-guided follicle aspiration sessions. Semen underwent physical and morphological evaluation, and samples were stored for further computer-assisted sperm analysis. The COC recovered were evaluated according to morphology and those classified as viable were sent to an IVEP laboratory. Results: Diflubenzuron had no effect (P > 0.05) on average body weight or in any blood hematological or biochemical endpoints, regardless of gender. In experiment 1, there was no difference (P > 0.05) between DIF and CG groups for sperm concentration, morphology, or kinetics. In experiment 2, there was also no effect of diflubenzuron on the number of total, viable, or grade I oocytes, as well as on cleavage or blastocyst rates (P > 0.05). Discussion: In summary, the oral administration of diflubenzuron, within the recommended dose, has no short-term negative effects on sperm production and quality or on oocyte yield and developmental potential in vitro, in cattle.
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PURPOSE: To identify systemic and/or ophthalmologic predictors of proliferative sickle retinopathy. METHODS: Cross-sectional study comparing clinical, laboratory, and structural choriorretinal aspects between sickle cell disease patients with and without proliferative retinopathy. Patients underwent complete systemic and ophthalmologic evaluation. Enhanced depth spectral domain optical coherence tomography with choroidal binarization and optic coherence tomography angiography were performed and choriorretinal vascular components were compared. RESULTS: Forty-five eyes from 45 sickle cell patients were included. Ninety-one percent of patients were diagnosed with sickle cell retinopathy, 29% with proliferative retinopathy. Mean corpuscular volume, lactate dehydrogenase, and percentage of fetal hemoglobin were reduced in the subgroup of patients with proliferative retinopathy when compared with patients without proliferative retinopathy (p ≤ 0.001; p = 0.04; p ≤ 0.001, respectively). The best predictor of proliferative retinopathy was mean corpuscular volume (AUC = 0.842; p = 0.001), followed by the percentage of fetal hemoglobin (AUC = 0.763, p = 0.009) and lactate dehydrogenase (AUC curve = 0.706; p = 0.039). No differences were found between groups in the quantitative analysis of retinal vascularization using OCTA and choroidal vascularization using OCT (p ≥ 0.05). CONCLUSION: Fetal hemoglobin and mean corpuscular volume may be good predictors of proliferative sickle retinopathy. The association between proliferative retinopathy and reduced levels of lactate dehydrogenase and mean corpuscular volume points to hypoxia and not hemolysis as a possible driving force in its pathophysiology.
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Identifying individuals and factors associated with severe cases of COVID-19 is crucial as the pandemic continues to spread globally. Effective biomarkers for predicting severe cases are essential for optimizing clinical management, therapy, and preventing unfavorable outcomes. This exploratory observational study aimed to investigate the expression of dysregulated immune response genes (ARG1, NOS2, ITGA4, and SELPLG) in total leukocytes, plasmatic levels of P-selectin and PSGL-1, and their clinical associations in patients with mild and severe COVID-19. Data from 117 confirmed COVID-19 patients (severe = 58, mild = 59) were collected upon admission. Gene expression was measured using RT-qPCR, and plasma protein levels assessed with ELISA assay. The severe COVID-19 patient group had a higher median age of 62.0 (p = 0.0001), a higher proportion of black individuals (86.2%, p < 0.0001), and more males (65.5%, p = 0.007). The neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) were significantly higher in the severe COVID-19 patient group (p < 0.0001), indicating ongoing systemic inflammation. Severe COVID-19 patients also exhibited increased expression of ARG1 (p < 0.05) and SELPLG (p < 0.0001) genes, as well as higher concentrations of soluble P-selectin (p < 0.005) and PSGL-1 (p < 0.05) proteins. Multivariate analysis revealed that NLR, PLR, the expression of SELPLG and sPSGL-1 were independent predictors of COVID-19 severity. In conclusion, this study suggests that biomarkers of endothelial dysfunction and dysregulated leukocyte responses are associated with COVID-19 severity, serving as promising predictive tools for optimizing clinical management and patient monitoring.
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COVID-19 , Doenças Vasculares , Masculino , Humanos , Selectina-P/metabolismo , COVID-19/metabolismo , Contagem de Plaquetas , Biomarcadores , Neutrófilos/metabolismo , Imunidade , Estudos RetrospectivosRESUMO
OBJECTIVE: To evaluate handgrip strength (HGS) as a diagnostic tool for frailty risk in elderly patients with asthma, as well as to investigate the prevalence of frailty in this population. METHODS: This was a cross-sectional study including 96 patients ≥ 60 years of age diagnosed with moderate to severe asthma and treated at a tertiary referral center in Brazil. We measured HGS using a calibrated hydraulic hand dynamometer. We used a frailty scale and the AUC to assess the diagnostic accuracy of the HGS test. RESULTS: The median age of participants was 67 years. Most (78%) were women and non-White (91%) of low socioeconomic status. HGS identified those at risk for frailty, with an AUC of 71.6% (61.5-80.4%; p < 0.002), as well as a sensitivity of 73.58% and a specificity of 67.53%, on the basis of a cutoff of ≤ 19 kgf. CONCLUSIONS: HGS appears to be a simple, reliable tool for clinicians to determine frailty risk in older asthma patients in a point-of-care setting.
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Asma , Fragilidade , Humanos , Feminino , Idoso , Masculino , Força da Mão , Fragilidade/diagnóstico , Estudos Transversais , Brasil/epidemiologia , Asma/diagnósticoRESUMO
AIM: Preventive approaches to oral health diseases, mainly dental caries, require individual and collective policies. Thus, this review was conducted to identify the primary prevention methods of dental caries in adults to improve oral health at the clinical and community levels. METHODS: This review followed the PICO strategy with the research question: "What are the methods of primary prevention of dental caries, in adults, for improving and maintaining oral health integrating clinical and community-based strategies?" Electronic screening was carried out by two independent reviewers in five databases (MedLine/PubMed, SciELO, Web of Science, Cochrane Library, and LILACS) to find relevant publications between 2015-2022. We applied eligibility criteria for selection of the articles. The following MeSH terms were used: "Primary Prevention"; "Adult"; "Oral Health"; "Dental Caries"; "Fluorides, Topical"; "Fluoride Varnishes"; "Pit and Fissure Sealants"; "Preventive Dentistry". Although the term "Prevention strategy" is not a MeSH descriptor, several correlated terms appeared and were used in the search engines: "Preventative Care", "Disease Prevention, Primary", and "Prevention, Primary". The tool provided by the JBI organization (Joanna Briggs Institute) was used to assess the quality of the included studies. RESULTS: Nine studies were included. Overall, it was found that the main primary prevention methods applied in dentistry in adults are the application of pit and fissure sealants, topical application of fluoride performed in the dental clinic, use of fluoridated toothpaste, mouthwash with chlorhexidine at home, use of xylitol, the recommendation for regular appointments with the dentist, and the need to inform patients about the saliva buffer capacity and adoption of a non-cariogenic diet. For that purpose, preventive policies should be taken to prevent dental caries. These include three major challenges: providing the adult population with more knowledge regarding their oral health, empowering patients through adopting healthy lifestyles, and developing new preventive strategies and awareness campaigns aimed at the adult population to promote proper oral health habits. CONCLUSIONS: A small number of studies were found whose participants were adult patients. There was some consistency regarding primary prevention methods in our studies. However, good quality randomized control studies are still required to define the best intervention strategies for adult caries prevention.
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Crotalus venom has broad biological activity, including neurotoxic, myotoxic, hematologic, and cytotoxic compounds that induce severe systemic repercussions. We evaluated the pathophysiological and clinical significance of Crotalus durissus cascavella (Cdc) venom-induced pulmonary impairment in mice. We conducted a randomized experimental study, involving 72 animals intraperitoneally inoculated with saline solution in the control group (CG), as well as venom in the experimental group (EG). The animals were euthanized at predetermined intervals (1 h, 3 h, 6 h, 12 h, 24 h, and 48 h), and lung fragments were collected for H&E and Masson histological analysis. The CG did not present inflammatory alterations in pulmonary parenchyma. In the EG, interstitial and alveolar swelling, necrosis, septal losses followed by alveolar distensions, and areas of atelectasis in the pulmonary parenchyma were observed after three hours. The EG morphometric analysis presented pulmonary inflammatory infiltrates at all time intervals, being more significant at three and six (p = 0.035) and six and 12 h (p = 0.006). The necrosis zones were significant at intervals of one and 24 h (p = 0.001), one and 48 h (p = 0.001), and three and 48 h (p = 0.035). Crotalus durissus cascavella venom induces a diffuse, heterogeneous, and acute inflammatory injury in the pulmonary parenchyma, with potential clinical implications for respiratory mechanics and gas exchange. The early recognition and prompt treatment of this condition are essential to prevent further lung injury and to improve outcomes.
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Relevância Clínica , Venenos de Crotalídeos , Animais , Camundongos , Venenos de Crotalídeos/toxicidade , Crotalus , Modelos Animais de Doenças , Pulmão , NecroseRESUMO
ABSTRACT Objective: To evaluate handgrip strength (HGS) as a diagnostic tool for frailty risk in elderly patients with asthma, as well as to investigate the prevalence of frailty in this population. Methods: This was a cross-sectional study including 96 patients ≥ 60 years of age diagnosed with moderate to severe asthma and treated at a tertiary referral center in Brazil. We measured HGS using a calibrated hydraulic hand dynamometer. We used a frailty scale and the AUC to assess the diagnostic accuracy of the HGS test. Results: The median age of participants was 67 years. Most (78%) were women and non-White (91%) of low socioeconomic status. HGS identified those at risk for frailty, with an AUC of 71.6% (61.5-80.4%; p < 0.002), as well as a sensitivity of 73.58% and a specificity of 67.53%, on the basis of a cutoff of ≤ 19 kgf. Conclusions: HGS appears to be a simple, reliable tool for clinicians to determine frailty risk in older asthma patients in a point-of-care setting.
RESUMO Objetivo: Avaliar a força de preensão manual (FPM) como ferramenta diagnóstica de risco de fragilidade em pacientes idosos com asma e investigar a prevalência de fragilidade nessa população. Métodos: Estudo transversal com 96 pacientes com idade ≥ 60 anos e diagnóstico de asma moderada a grave, atendidos em um centro terciário de referência no Brasil. Medimos a FPM com um dinamômetro hidráulico manual calibrado. Usamos uma escala de fragilidade e a ASC para avaliar a precisão diagnóstica do teste de FPM. Resultados: A mediana da idade dos participantes foi de 67 anos. A maioria eram mulheres (78%) não brancas (91%) cujo nível socioeconômico era baixo. O ponto de corte de FPM ≤ 19 kgf identificou os participantes que apresentavam risco de fragilidade, com ASC = 71,6% (61,5-80,4%; p < 0,002), sensibilidade = 73,58% e especificidade = 67,53%. Conclusões: A FPM parece ser uma ferramenta simples e confiável para determinar, no próprio local de atendimento médico, o risco de fragilidade em pacientes idosos com asma.
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Background and aim: COVID-19 is a respiratory disease caused by the new coronavirus SARS-CoV-2, for which the first cases were reported in China, by December 2019. The spectrum of clinical presentations is wide, ranging from asymptomatic cases to a severe acute respiratory syndrome, sometimes with multiple systems involvement. Viral infections, including those related to respiratory virus, may cause hearing loss and, by extent, considering its pathophysiology, tinnitus. A systematic review on inner ear related symptoms in patients with COVID-19 reported 4.5% occurrence rate of tinnitus, with high variance of prevalence between the studies. Our aim is to further explore the relationship between COVID-19 and tinnitus. For this purpose we analyzed a sample of people who had suffered from a COVID-19 infection in the city of Volta Redonda, Brazil. In detail, we compared those with new onset tinnitus during or after the COVID-19 infection with those without tinnitus and those with tinnitus onset before the COVID-19 infection. Methods: Fifty-seven patients over 18 years old and previously diagnosed with COVID-19 confirmed by a RT-PCR test were included. Patients were subdivided in three groups: no tinnitus (NT), tinnitus that already existed before COVID-19 (chronic tinnitus, CT) and tinnitus that arose during or after COVID-19 (post-COVID-19 tinnitus, PCT). Data concerning COVID-19 symptoms, drugs prescribed for COVID-19, tinnitus characteristics, comorbidities and other otological symptoms were collected. For all the patients, tonal audiometry and otoacoustic emissions were performed. Tinnitus patients fulfilled the Tinnitus Handicap Inventory (THI) and visual-analog scales (VAS) for loudness and distress. Patients with CT answered a simple question about the worsening of their tinnitus after COVID-19. Results: PCT was reported by 19.3% of the patients, while 22.8% reported CT. No statistical difference was found between CT and PCT concerning hearing function, tinnitus characteristics and tinnitus distress. There was also no statistically significant difference between PCT and NT with respect to COVID-19 symptoms and pharmacological COVID-19 treatment. Patients with CT reported worsening of their tinnitus after COVID-19. Conclusion: As with other viral infections, inner ear symptoms may be associated with COVID-19. In our sample patients with tinnitus onset before COVID-19 and those with tinnitus onset during or after COVID-19 did not differ significantly in their clinical characteristics and their hearing function, suggesting that tinnitus occurring in the context of a COVID-19 infection is not related to a unique pathophysiological mechanism. The comparison of COVID-19 patients, who developed tinnitus with those who did not develop tinnitus did not reveal any differences in COVID-19 symptoms or COVID-19 treatment. Thus, there was no hint, that a specific expression of COVID-19 is closely related to post COVID-19 tinnitus onset. Although some drugs used to treat tinnitus are known to damage the inner ear cells (especially hydroxychloroquine), we did not see any relationship between the intake of these drugs and tinnitus onset, eventually due to the short prescription time and low doses. Among those patients who had tinnitus before COVID-19 30,8% reported worsening after COVID-19. Overall, tinnitus emerging in the context of a COVID-19 infection seems not to differ from tinnitus unrelated to COVID-19. For further exploring the relationship of tinnitus and COVID-19, large population based studies are warranted.
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The purpose of this study was to characterize the reproductive physiology, oocyte competence, and chromatin compaction in Nelore calves in the early-prepubertal period (EPP) and the intermediate-prepubertal period (IPP). Calves aged 2-5 (EPP) and 8-11 months old (IPP) were assigned to Trial 1 (morpho-physiological-endocrine evaluations, n = 8) or Trial 2 (oocyte donors, n = 8) vs. the respective control groups of cows (n = 8, each). All morphological endpoints, except the antral follicle count, increased from the EPP to the IPP. The EPP LH-FSH plasma concentrations were similar to cows, whereas LH was lower and FSH was higher in the IPP than in cows. . Cows produced more Grade I (12.9% vs. 4.1% and 1.7%) and fewer Grade III COC (30.1% vs. 44.5% and 49.0%) than the EPP and IPP calves, respectively. The IPP calves' oocyte diameter was similar to those from cows but greater than those from EPP females (124.8 ± 8.5 and 126.0 ± 7.5 µm vs. 121.3 ± 7.5 µm, respectively). The expression of the chromatin compaction-related gene HDAC3 was downregulated in calves. The proportion of the blastocyst rate to the controls was lower in EPP than in IPP calves (43.7% vs. 78.7%, respectively). Progressive oocyte competence was found during the prepubertal period, which can help to decide whether to recover oocytes from calves.