Endogenous androgens diminish food intake and activation of orexin A neurons in response to reduced glucose availability in male rats

Sex steroids modify feeding behavior and body weight regulation, and androgen reportedly augments food intake and body weight gain. To elucidate the role of endogenous androgens in the feeding regulation induced by reduced glucose availability, we examined the effect of gonadectomy (orchiectomy) on food intake and orexin A neuron’s activity in the lateral hypothalamic/perifornical area (LH/PFA) in response to reduced glucose availability (glucoprivation) induced by 2-deoxy-d-glucose (2DG) administration in male rats. Rats (7W) were bilaterally orchiectomized (ORX group) or sham operated (Sham group). Seventeen days after the surgery, food intake response to 2DG (400 mg/kg, i.v.) was measured for 4 h after the infusion. The same experiment was performed for the immunohistochemical examination of c-Fos-expressing orexin A neurons in the LH/PFA and c-Fos expression in the arcuate nucleus (Arc). Food intake induced by glucoprivation was greater in the ORX group than the Sham group, and the glucoprivation-induced food intake was inversely correlated with plasma testosterone concentration. Glucoprivation stimulated c-Fos expression of the orexin A neurons at the LH/PFA and c-Fos expression in the dorsomedial Arc. The number and percentage of c-Fos-expressing orexin A neurons in the LH/PFA and c-Fos expression in the dorsomedial Arc were significantly higher in the ORX group than the Sham group. This indicates that endogenous androgen, possibly testosterone, diminishes the food intake induced by reduced glucose availability, possibly via the attenuated activity of orexin A neuron in the LH/PFA and neurons in the dorsomedial Arc

ALOPECIA ANDROGENÉTICA FEMININA – O IMPACTO NA AUTOESTIMA

A Alopecia androgenética (AAG) é uma doença capilar crônica conhecida popularmente como calvície, que pode acometer homens e mulheres. Mesmo sendo considerada de carácter benigno, pode ter um impacto psicológico significativo, principalmente nas mulheres, devido à importância cultural e social dada aos cabelos femininos, no qual, é comum associar-se à beleza ideal. A perda dos cabelos pode afetar negativamente a autoestima e consequentemente a qualidade de vida dessa população, levando, por exemplo, à ansiedade e depressão. Existem opções de tratamento disponíveis, como o Minoxidil tópico e injetável, Finasterida oral, terapia com laser de baixa intensidade, terapias hormonais, nutracêuticos, PRP (plasma rico em plaquetas), exossomos, que são eficazes no tratamento da AAG. No entanto, muitas opções de tratamento têm efeitos colaterais, baixa eficácia ou são inacessíveis financeiramente. É importante entender suas causas e mecanismos para desenvolver melhores abordagens de tratamento, que combinados a um maior entendimento sobre as consequências psicológicas dessa condição, podem contribuir para desenvolver tratamentos holísticos com resultados mais eficazes, melhorando a qualidade de vida. Esse estudo tem como objetivo compreender melhor a AAG, seus impactos na autoestima feminina, além de revisar as técnicas utilizadas para seu tratamento, considerando possíveis combinações entre elas.Androgenetic alopecia (AGA) is a chronic hair disease popularly known as baldness, which can affect men and women. Even though it is considered benign in nature, it can have a significant psychological impact, especially on women, due to the cultural and social importance given to female hair, which is commonly associated with ideal beauty. Hair loss can negatively affect self-esteem and consequently the quality of life of this population, leading, for example, to anxiety and depression. There are treatment options available, such as topical minoxidil and low-level laser therapy, which are effective in treating AGA. However, many treatment options have side effects, low efficacy or are financially inaccessible. It is important to understand its causes and mechanisms to develop better treatment approaches, combined with a greater understanding of the psychological consequences of this condition, which can contribute to developing holistic treatments with more effective results, improving quality of life. This study aims to better understand AGA, its impacts on female self-esteem, in addition to reviewing the techniques used for its treatment, considering possible combinations between them.La alopecia androgenética (AGA) es una enfermedad capilar crónica conocida popularmente como calvicie, que puede afectar a hombres y mujeres. Aunque se considera de naturaleza benigna, puede tener un impacto psicológico significativo, especialmente en las mujeres, debido a la importancia cultural y social que se le da al cabello femenino, que comúnmente se asocia con la belleza ideal. La caída del cabello puede afectar negativamente a la autoestima y, en consecuencia, a la calidad de vida de esta población, provocando, por ejemplo, ansiedad y depresión. Hay opciones de tratamiento disponibles, como el minoxidil tópico y la terapia con láser de baja intensidad, que son eficaces para tratar el AGA. Sin embargo, muchas opciones de tratamiento tienen efectos secundarios, baja eficacia o son económicamente inaccesibles. Es importante comprender sus causas y mecanismos para desarrollar mejores enfoques de tratamiento, combinados con una mayor comprensión de las consecuencias psicológicas de esta condición, que pueden contribuir al desarrollo de tratamientos holísticos con resultados más efectivos, mejorando la calidad de vida. Este estudio tiene como objetivo comprender mejor la AGA, sus impactos en la autoestima femenina, además de revisar las técnicas utilizadas para su tratamiento, considerando posibles combinaciones entre ellas.A Alopecia androgenética (AAG) é uma doença capilar crônica conhecida popularmente como calvície, que pode acometer homens e mulheres. Mesmo sendo considerada de carácter benigno, pode ter um impacto psicológico significativo, principalmente nas mulheres, devido à importância cultural e social dada aos cabelos femininos, no qual, é comum associar-se à beleza ideal. A perda dos cabelos pode afetar negativamente a autoestima e consequentemente a qualidade de vida dessa população, levando, por exemplo, à ansiedade e depressão. Existem opções de tratamento disponíveis, como o Minoxidil tópico e injetável, Finasterida oral, terapia com laser de baixa intensidade, terapias hormonais, nutracêuticos, PRP (plasma rico em plaquetas), exossomos, que são eficazes no tratamento da AAG. No entanto, muitas opções de tratamento têm efeitos colaterais, baixa eficácia ou são inacessíveis financeiramente. É importante entender suas causas e mecanismos para desenvolver melhores abordagens de tratamento, que combinados a um maior entendimento sobre as consequências psicológicas dessa condição, podem contribuir para desenvolver tratamentos holísticos com resultados mais eficazes, melhorando a qualidade de vida. Esse estudo tem como objetivo compreender melhor a AAG, seus impactos na autoestima feminina, além de revisar as técnicas utilizadas para seu tratamento, considerando possíveis combinações entre elas

A multicenter randomized controlled trial to evaluate the efficacy and safety of nelfinavir in patients with mild COVID-19

Nelfinavir, an orally administered inhibitor of human immunodeficiency virus protease, inhibits the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro. We conducted a randomized controlled trial to evaluate the clinical efficacy and safety of nelfinavir in patients with SARS-CoV-2 infection. We included unvaccinated asymptomatic or mildly symptomatic adult patients who tested positive for SARS-CoV-2 infection within 3 days before enrollment. The patients were randomly assigned (1:1) to receive oral nelfinavir (750 mg; thrice daily for 14 days) combined with standard-of-care or standard-of-care alone. The primary endpoint was the time to viral clearance, confirmed using quantitative reverse-transcription PCR by assessors blinded to the assigned treatment. A total of 123 patients (63 in the nelfinavir group and 60 in the control group) were included. The median time to viral clearance was 8.0 (95% confidence interval [CI], 7.0 to 12.0) days in the nelfinavir group and 8.0 (95% CI, 7.0 to 10.0) days in the control group, with no significant difference between the treatment groups (hazard ratio, 0.815; 95% CI, 0.563 to 1.182; P = 0.1870). Adverse events were reported in 47 (74.6%) and 20 (33.3%) patients in the nelfinavir and control groups, respectively. The most common adverse event in the nelfinavir group was diarrhea (49.2%). Nelfinavir did not reduce the time to viral clearance in this setting. Our findings indicate that nelfinavir should not be recommended in asymptomatic or mildly symptomatic patients infected with SARS-CoV-2. The study is registered with the Japan Registry of Clinical Trials (jRCT2071200023). IMPORTANCE The anti-HIV drug nelfinavir suppresses the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro. However, its efficacy in patients with COVID-19 has not been studied. We conducted a multicenter, randomized controlled trial to evaluate the efficacy and safety of orally administered nelfinavir in patients with asymptomatic or mildly symptomatic COVID-19. Compared to standard-of-care alone, nelfinavir (750 mg, thrice daily) did not reduce the time to viral clearance, viral load, or the time to resolution of symptoms. More patients had adverse events in the nelfinavir group than in the control group (74.6% [47/63 patients] versus 33.3% [20/60 patients]). Our clinical study provides evidence that nelfinavir, despite its antiviral effects on SARS-CoV-2 in vitro, should not be recommended for the treatment of patients with COVID-19 having no or mild symptoms

Pathogenic variants in SLF2 and SMC5 cause segmented chromosomes and mosaic variegated hyperploidy

Embryonic development is dictated by tight regulation of DNA replication, cell division and differentiation. Mutations in DNA repair and replication genes disrupt this equilibrium, giving rise to neurodevelopmental disease characterized by microcephaly, short stature and chromosomal breakage. Here, we identify biallelic variants in two components of the RAD18-SLF1/2-SMC5/6 genome stability pathway, SLF2 and SMC5, in 11 patients with microcephaly, short stature, cardiac abnormalities and anemia. Patient-derived cells exhibit a unique chromosomal instability phenotype consisting of segmented and dicentric chromosomes with mosaic variegated hyperploidy. To signify the importance of these segmented chromosomes, we have named this disorder Atelís (meaning - incomplete) Syndrome. Analysis of Atelís Syndrome cells reveals elevated levels of replication stress, partly due to a reduced ability to replicate through G-quadruplex DNA structures, and also loss of sister chromatid cohesion. Together, these data strengthen the functional link between SLF2 and the SMC5/6 complex, highlighting a distinct role for this pathway in maintaining genome stability

Decline in subarachnoid haemorrhage volumes associated with the first wave of the COVID-19 pandemic

BACKGROUND: During the COVID-19 pandemic, decreased volumes of stroke admissions and mechanical thrombectomy were reported. The study\u27s objective was to examine whether subarachnoid haemorrhage (SAH) hospitalisations and ruptured aneurysm coiling interventions demonstrated similar declines. METHODS: We conducted a cross-sectional, retrospective, observational study across 6 continents, 37 countries and 140 comprehensive stroke centres. Patients with the diagnosis of SAH, aneurysmal SAH, ruptured aneurysm coiling interventions and COVID-19 were identified by prospective aneurysm databases or by International Classification of Diseases, 10th Revision, codes. The 3-month cumulative volume, monthly volumes for SAH hospitalisations and ruptured aneurysm coiling procedures were compared for the period before (1 year and immediately before) and during the pandemic, defined as 1 March-31 May 2020. The prior 1-year control period (1 March-31 May 2019) was obtained to account for seasonal variation. FINDINGS: There was a significant decline in SAH hospitalisations, with 2044 admissions in the 3 months immediately before and 1585 admissions during the pandemic, representing a relative decline of 22.5% (95% CI -24.3% to -20.7%, p\u3c0.0001). Embolisation of ruptured aneurysms declined with 1170-1035 procedures, respectively, representing an 11.5% (95%CI -13.5% to -9.8%, p=0.002) relative drop. Subgroup analysis was noted for aneurysmal SAH hospitalisation decline from 834 to 626 hospitalisations, a 24.9% relative decline (95% CI -28.0% to -22.1%, p\u3c0.0001). A relative increase in ruptured aneurysm coiling was noted in low coiling volume hospitals of 41.1% (95% CI 32.3% to 50.6%, p=0.008) despite a decrease in SAH admissions in this tertile. INTERPRETATION: There was a relative decrease in the volume of SAH hospitalisations, aneurysmal SAH hospitalisations and ruptured aneurysm embolisations during the COVID-19 pandemic. These findings in SAH are consistent with a decrease in other emergencies, such as stroke and myocardial infarction

The Constrained Maximal Expression Level Owing to Haploidy Shapes Gene Content on the Mammalian X Chromosome.

X chromosomes are unusual in many regards, not least of which is their nonrandom gene content. The causes of this bias are commonly discussed in the context of sexual antagonism and the avoidance of activity in the male germline. Here, we examine the notion that, at least in some taxa, functionally biased gene content may more profoundly be shaped by limits imposed on gene expression owing to haploid expression of the X chromosome. Notably, if the X, as in primates, is transcribed at rates comparable to the ancestral rate (per promoter) prior to the X chromosome formation, then the X is not a tolerable environment for genes with very high maximal net levels of expression, owing to transcriptional traffic jams. We test this hypothesis using The Encyclopedia of DNA Elements (ENCODE) and data from the Functional Annotation of the Mammalian Genome (FANTOM5) project. As predicted, the maximal expression of human X-linked genes is much lower than that of genes on autosomes: on average, maximal expression is three times lower on the X chromosome than on autosomes. Similarly, autosome-to-X retroposition events are associated with lower maximal expression of retrogenes on the X than seen for X-to-autosome retrogenes on autosomes. Also as expected, X-linked genes have a lesser degree of increase in gene expression than autosomal ones (compared to the human/Chimpanzee common ancestor) if highly expressed, but not if lowly expressed. The traffic jam model also explains the known lower breadth of expression for genes on the X (and the Z of birds), as genes with broad expression are, on average, those with high maximal expression. As then further predicted, highly expressed tissue-specific genes are also rare on the X and broadly expressed genes on the X tend to be lowly expressed, both indicating that the trend is shaped by the maximal expression level not the breadth of expression per se. Importantly, a limit to the maximal expression level explains biased tissue of expression profiles of X-linked genes. Tissues whose tissue-specific genes are very highly expressed (e.g., secretory tissues, tissues abundant in structural proteins) are also tissues in which gene expression is relatively rare on the X chromosome. These trends cannot be fully accounted for in terms of alternative models of biased expression. In conclusion, the notion that it is hard for genes on the Therian X to be highly expressed, owing to transcriptional traffic jams, provides a simple yet robustly supported rationale of many peculiar features of X's gene content, gene expression, and evolution

Deodorant Activity of Black Cumin Seed Essential Oil against Garlic Organosulfur Compound

The deodorant activity of black cumin (Nigella sativa L.) seed, a spice used to flavor curry and vegetable foods in Southwest Asia, against garlic (Allium sativum L.) organosulfur compounds related to human malodor was evaluated. Black cumin seed essential oil showed remarkable deodorant activity against garlic essential oil. The mode of action of this deodorant activity was presumed to be that black cumin seed essential oil covalently reacted with the organosulfur compounds in garlic. Therefore, thymoquinone, which is a major constituent in black cumin seed essential oil, and allyl mercaptan, which is one of the organosulfur compounds produced by cutting garlic, were reacted in vitro, and the products were purified and elucidated using spectroscopic data. As a result, these substances were identified as different allyl mercaptan adducts to dihydrothymoquinone. This chemical reaction was presumed to play a key role in the deodorant activity of black cumin seed essential oil

ANÁLISE DO BALANÇO SOCIAL DAS EMPRESAS DE PAPEL E CELULOSE

Não são só as empresas que compreendem a importância da Responsabilidade sócio-ambiental e a necessidade de um desenvolvimento econômico sustentável, a questão ambiental e social também vem sendo frequentemente discutida entre toda a sociedade, que deixou a passividade, se tornou ativa e vem almejando por informações transparentes com relação a essas questões. Neste sentido o Balanço Social mostra informações tanto qualitativas como quantitativas sobre como a empresa está desempenhando sua função sócio-ambiental na sociedade que está inserida. As indústrias de papel e celulose exigem o uso intensivo de energia e água e dependem totalmente de fibras naturais e recicladas, além de emitirem uma quantidade significativa de poluentes, gerando assim, impactos ambientais que podem implicar na possibilidade de alterações significantes no desempenho econômico e financeiro deste setor. Diante deste fato, esse trabalho analisou como está sendo feita a evidenciação das informações sócio-ambientais nos relatórios anuais destas empresas, segundo o modelo proposto pelo IBASE, e constatou que há deficiências na divulgação de tais informações