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José William Zucchi,1 Estefânia Aparecida Thomé Franco,1 Thomas Schreck,2 Maria Helena Castro e Silva,3 Sandro Rogerio dos Santos Migliorini,3 Thaís Garcia,1 Gustavo Augusto Ferreira Mota,1 Bruna Evelyn Bueno de Morais,1 Luiz Henrique Soares Machado,1 Ana Natália Ribeiro Batista,1 Sergio Alberto Rupp de Paiva,1 Irma de Godoy,1 Suzana Erico Tanni1 1Pulmonology Division of Botucatu Medical School, São Paulo State University (UNESP), Botucatu, Brazil; 2Ostbayerische Technische Hochschule Regensburg (OTH Regensburg), Faculty of Business Studies, Regensburg, German; 3Pulmonology Division of Federal University of Triângulo Mineiro, Uberaba, BrazilCorrespondence: José William Zucchi Email jwzucchi@hotmail.comBackground: Chronic obstructive pulmonary disease (COPD) has a functional definition. However, differences in clinical characteristics and systemic manifestations make COPD a heterogeneous disease and some manifestations have been associated with different risks of acute exacerbations, hospitalizations, and death.Objective: Therefore, the objective of the study was to evaluate possible clinical clusters in COPD at two study centers in Brazil and identify the associated exacerbation and mortality rate during 1 year of follow-up.Methods: We included patients with COPD and all underwent an evaluation composed of the Charlson Index, body mass index (BMI), current pharmacological treatment, smoking history (packs-year), history of exacerbations/hospitalizations in the last year, spirometry, six-minute walking test (6MWT), quality of life questionnaires, dyspnea, and hospital anxiety and depression scale. Blood samples were also collected for measurements of C-reactive protein (CRP), blood gases, laboratory analysis, and blood count. For the construction of the clusters, 13 continuous variables of clinical importance were considered: hematocrit, CRP, triglycerides, low density lipoprotein, absolute number of peripheral eosinophils, age, pulse oximetry, BMI, forced expiratory volume in the first second, dyspnea, 6MWD, total score of the Saint George Respiratory Questionnaire and packs-year of smoking. We used the Ward and K-means methods and determined the best silhouette value to identify similarities of individuals within the cluster (cohesion) in relation to the other clusters (separation). The number of clusters was determined by the heterogeneity values of the cluster, which in this case was determined as four clusters.Results: We evaluated 301 COPD patients and identified four different groups of COPD patients. The first cluster (203 patients) was characterized by fewer symptoms and lower functional severity of the disease, the second cluster by higher values of peripheral eosinophils, the third cluster by more systemic inflammation and the fourth cluster by greater obstructive severity and worse gas exchange. Cluster 2 had an average of 959± 3 peripheral eosinophils, cluster 3 had a higher prevalence of nutritional depletion (46.1%), and cluster 4 had a higher BODE index. Regarding the associated comorbidities, we found that only obstructive sleep apnea syndrome and pulmonary thromboembolism were more prevalent in cluster 4. Almost 50% of all patients presented an exacerbation during 1 year of follow-up. However, it was higher in cluster 4, with 65% of all patients having at least one exacerbation. The mortality rate was statistically higher in cluster 4, with 26.9%, vs 9.6% in cluster 1.Conclusion: We could identify four clinical different clusters in these COPD populations, that were related to different clinical manifestations, comorbidities, exacerbation, and mortality rate. We also identified a specific cluster with higher values of peripheral eosinophils.Keywords: COPD, eosinophils, cluster analysis, COPD phenotype, lung function

BACKGROUND & AIMS: Determining the caloric expenditure of overweight (Body mass index - BMI from 25-29.9 kg/m(2)) or obese (BMI> or =30 kg/m(2)) patients is a difficult task. The importance of the measurement using indirect calorimetry (IC) is to avoid the administration of an inadequate caloric load, which can increase clinical morbidity. The aim of this study was to compare the resting energy expenditure (REE) obtained by IC with that estimated by the Harris-Benedict (HB) and the Ireton-Jones (IJ) equations and a fixed amount of 21 kcal/kg of body weight, using actual, average and adjusted weights. METHODS: A total of 71 IC measurements were prospectively performed in 44 patients using the 'DELTATRAC II' calorimeter. In 53 of the measurements the patients were on mechanical ventilation and 18 were performed using the canopy, in the fasting state and 24h after achieving calculated caloric requirements. RESULTS: The best REE prediction value in the fasting state was obtained with the HB equation using the actual body weight (HB/ABW), 1873+/-484 kcal/day (p=0.49) when compared to the REE of 1798+/-495 kcal/day measured by IC. After achieving caloric needs, the best REE prediction values were using the HB/ABW equation, 1873+/-484 kcal/day (p=0.56) and the IJ equation with the adjusted body weight, 2103+/-580 kcal/day (p=0.19) when compared to 1948+/-507 kcal/day measured by IC. Although, when the above results were plotted on the Bland and Altman limits of agreement test their average bias were low, but the ranges of their absolute values from the observed average agreement were large, > or =531 kcal. CONCLUSION: From these data we can conclude that even though the average values obtained with the equations utilized to predict the REE for this population, showed good correlation with those by IC, as they had the best comparative absolute results, however they demonstrated an unacceptable variability when matched to the measured REE values. [ABSTRACT FROM AUTHOR]

We sought to identify and understand the health care needs of young people living with HIV/AIDS, particularly in terms of their psychosocial well-being. We conducted a qualitative analysis of HIV-positive young people and their caregivers, focusing on the implications of an HIV diagnosis for health care needs. Stigma was a recurrent issue that arose in the interviews conducted with the respondents, and it was evident that youths had been denied many rights related to health. We concluded that young people living with HIV need comprehensive care based on a human rights approach. In this regard, we offer some practical recommendations for health programs. [ABSTRACT FROM AUTHOR]

Background: High-risk pregnancies and birth defects are often greater within communities of color where resources for a healthy pregnancy are generally lacking. Infant and maternal mortality, preterm birth, and instances of increased developmental and physical defects are related to environmental exposures (e.g., pesticides, lead in water, wildfire smoke), dietary additives, and lack of access to adequate healthcare. More frequently people of color and other under-served groups, are affected by historical inequality and unconscious bias. Compounding these disparities, research into these issues and efforts to address them are poorly supported., Methods: The speakers in this symposium presented evidence for health disparities within communities of color to foster research aimed at identifying toxic levels of potentially hazardous dietary chemicals, or exposures in the pediatric population can focus on addressing the current inadequacy of translating scientific findings into enforceable policies., Results: The disparities discussed within this symposium highlighted key areas in desperate need of policy reform. In the United States, regulatory exposure levels have been established for lead exposures but frequently exceed these limits without mitigation. Neural tube defects can be prevented by a simple dietary solution such as fortification of staple foods with folic acid. Recent literature on gender as a social determinant of health has determined women suffer more negative health consequences due to social attitudes., Conclusions: Ultimately, this symposium provided an understanding of the experience of disadvantaged and marginalized persons during pregnancy, illustrated the disparities that exist in reproductive health, and described the need to address and prevent them., (© 2024 Wiley Periodicals LLC.)

Alzheimer's disease (AD) is a progressive neurodegenerative condition and the primary form of dementia among elderly people. The amyloidogenic hypothesis is the main theory that explains this phenomenon and describes the extracellular accumulation of amyloid beta (Aβ) peptides. Model organisms such as Drosophila melanogaster have been utilized to improve the understanding of this disease and its treatment. This study evaluated the effects of peptide and metabolic fractions of Brazilian kefir on a strain of D. melanogaster that expresses human Aβ peptide 1-42 in the eye. The parameters assessed included ommatidial organization, vacuole area, retinal thickness, and Aβ peptide quantification. The present study revealed that the fractions, particularly the peptidic fraction, significantly reduced the vacuole area and increased the retina thickness in treated flies, indicating an improvement in neurodegeneration phenotype. The peptidic fraction was also found to alter Aβ aggregation dynamics, inhibiting Aβ fibril formation, as revealed by dynamic light scattering. This study demonstrated that kefir fractions, particularly the peptidic fraction < 10 kDa, have the potential to regulate Aβ aggregation and alleviate neurodegeneration in a Drosophila melanogaster AD-like model. These findings suggest that kefir fractions could be viable for the bioprospection of novel drug prototypes for AD treatment, providing valuable insights into strategies targeting Aβ aggregation and neurodegeneration in AD., (© 2024. The Author(s).)

This study analyzed a recently developed bone substitute biomaterial made of chitosan-xanthanhydroxyapatite-graphene oxide (CXHAG). The CXHAG particles underwent in vitro structural and morphological characterization, and in vivo testing with or without osteogenic conditioned medium from mesenchymal stem cells. Aim: The aim of this study was to determine whether the CXHAG novel biomaterial, supplemented with conditioned medium from mesenchymal stem cells, could be useful for bone regeneration. Materials and Method: For the in vitro study, cells were incubated with 20mg of CXHAG granules for 24 hours and a MTT assay was performed to tests for cytotoxicity. For the in vivo study, critical size calvarial bone defects were created in twenty-five rats. One animal had the defect unfilled (Control Group-CG) and was euthanized after 42 days. Twelve rats received the CXHAG particles (Group 1-G1) and the other twelve received the CXHAG particles supplemented with the conditioned medium (Group 2-G2). All G1/G2 grafts were covered with a CXHAG membrane. G1/G2 animals were euthanized after 14 days (T1) or 42 days (T2). The specimens were processed and histologically evaluated. Results: SEM analysis of the CXHAG particles showed granules of 300-400μm, with a rough irregular surface. They were not cytotoxic to dental pulp stem cells in vitro. The CG specimen showed loose immature connective tissue and no bone formation at the center of the defect. G1 and G2 presented remnant biomaterial particles at both time points, but only G2 had bone formation at the enter of the defect. Conclusions: The conditioned medium had a positive effect on bone regeneration in rat calvarial critical size defects when associated with the novel bone substitute biomaterial., Competing Interests: The authors declare no conflicts of interest concerning the publication of this article, (SAIO.)

Background: Kefir is a complex microbial community that plays a critical role in the fermentation and production of bioactive peptides, and has health-improving properties. The composition of kefir can vary by geographic localization and weather, and this paper focuses on a Brazilian sample and continues previous work that has successful anti-Alzheimer properties. In this study, we employed shotgun metagenomics and peptidomics approaches to characterize Brazilian kefir further., Results: We successfully assembled the novel genome of Lactobacillus kefiranofaciens (LkefirU) and conducted a comprehensive pangenome analysis to compare it with other strains. Furthermore, we performed a peptidome analysis, revealing the presence of bioactive peptides encrypted by L. kefiranofaciens in the Brazilian kefir sample, and utilized in silico prospecting and molecular docking techniques to identify potential anti-Alzheimer peptides, targeting β-amyloid (fibril and plaque), BACE, and acetylcholinesterase. Through this analysis, we identified two peptides that show promise as compounds with anti-Alzheimer properties., Conclusions: These findings not only provide insights into the genome of L. kefiranofaciens but also serve as a promising prototype for the development of novel anti-Alzheimer compounds derived from Brazilian kefir., (© 2024. The Author(s).)

Open access new approach methods (NAM) in the US EPA ToxCast program and NTP Integrated Chemical Environment (ICE) were used to investigate activities of four neurotoxic pesticides: endosulfan, fipronil, propyzamide and carbaryl. Concordance of in vivo regulatory points of departure (POD) adjusted for interspecies extrapolation (AdjPOD) to modelled human Administered Equivalent Dose (AED Human ) was assessed using 3-compartment or Adult/Fetal PBTK in vitro to in vivo extrapolation. Model inputs were from Tier 1 (High throughput transcriptomics: HTTr, high throughput phenotypic profiling: HTPP) and Tier 2 (single target: ToxCast) assays. HTTr identified gene expression signatures associated with potential neurotoxicity for endosulfan, propyzamide and carbaryl in non-neuronal MCF-7 and HepaRG cells. The HTPP assay in U-2 OS cells detected potent effects on DNA endpoints for endosulfan and carbaryl, and mitochondria with fipronil (propyzamide was inactive). The most potent ToxCast assays were concordant with specific components of each chemical mode of action (MOA). Predictive adult IVIVE models produced fold differences (FD) < 10 between the AED Human and the measured in vivo AdjPOD. The 3-compartment model was concordant (i.e., smallest FD) for endosulfan, fipronil and carbaryl, and PBTK was concordant for propyzamide. The most potent AED Human predictions for each chemical showed HTTr, HTPP and ToxCast were mainly concordant with in vivo AdjPODs but assays were less concordant with MOAs. This was likely due to the cell types used for testing and/or lack of metabolic capabilities and pathways available in vivo . The Fetal PBTK model had larger FDs than adult models and was less predictive overall., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Alzheimer's disease (AD) is considered the leading cause of dementia in the elderly worldwide. It results in progressive memory loss and impairment of cognitive and motor skills, leading to a high degree of disability and dependence. The development of AD is associated with the accumulation of senile plaques in the brain, caused by the amyloidogenic pathway of the disease. Several genetic and biochemical events are linked to AD development, with oxidative stress being one of them. Due to the scarcity of drugs aimed at treating AD, antioxidant compounds are increasingly studied as therapeutic targets for the disease. In this study, we investigate the antioxidant and anti-Alzheimer potential of the Tetragonisca angustula (Jataí) pollen extract in a Drosophila melanogaster Alzheimer's model. For this purpose, we utilized a D. melanogaster AD-like model, which expresses genes related to the amyloidogenic pathway of Alzheimer's disease. We explored the floral origin of the collected pollen, conducted phytochemical prospecting, and evaluated its antioxidant capacity in vitro. In vivo experiments involved assessing the survival and climbing ability of the D. melanogaster AD-like model with various concentrations of the pollen extract. Our findings revealed that the pollen extract of Tetragonisca angustula exhibits a significant antioxidant response and high concentrations of important phytochemicals, such as flavonoids and polyphenols. Furthermore, it enhanced the survival rate of D. melanogaster, and across all concentrations tested, it improved the climbing ability of the flies after 15 days of treatment with methanolic pollen extract. Additionally, the pollen extract reduced the neurodegeneration index in histopathological analysis. Thus, our study demonstrates the potential of Tetragonisca angustula pollen as an important subject for further investigation, aiming to isolate molecules that could potentially serve as therapeutic targets for Alzheimer's disease., (© 2024. The Author(s).)

Background: Graft-versus-host disease (GVHD) is an immune system reaction that occurs in patients with a history of hematopoietic stem cell transplantation (HSCT), in which the grafted donor's cells attack those of the host. The objective of this systematic review was to present a study on oral squamous cell carcinoma (OSSC) that developed from GVHD areas in patients undergoing HSCT., Material and Methods: An electronic search was conducted in the databases PUBMED, WEB OF SCIENCE, SCOPUS, MEDLINE and SCIENCE DIRECT, according to PRISMA guidelines., Results: Of the 1582 results, 23 articles were included, resulting in 81 cases. The most common underlying disease for performing the transplant was Myeloid Leukemia (55.6%). The mean age was 39 years, with a predilection for males (64.2%). The tongue was the site of GVHD that most frequently underwent transformation to SCC (59.3%). The average time between transplantation and the development of GVHD was of approximately of 8 months, while the average period of development between transplantation and the development of OSCC was of approximately of 111 months. The most common treatment to GVHD was cyclosporine associated with corticosteroids., Conclusions: OSCCs arising from areas of GVHD present a different evolution from conventional oral carcinomas, since they affect younger patients, smoking and alcohol are not important etiological factors and finally because they present good prognosis, but further studies with larger number cases followed are needed to confirm our findings.

Mpox is caused by a zoonotic orthopoxvirus capable of infecting several animal species, including humans. The analysis of cases in the current outbreak showed that, differently from what happens in the classical disease, mpox has mostly affected men who have sex with men (MSM) and bisexuals, including a high proportion of people living with HIV/AIDS. The role of the immune system in fighting mpox has been discussed in literature and experts believe that immunity conferred by natural infection may be lifelong, advocating against the possibility of reinfection by monkeypox virus. This report presents a MSM couple living with HIV with cycles of mpox lesions after two different risk exposures. The clinical course of both cases, as well as the temporal and anatomical relationship between the second cycle of monkeypox virus lesions and the second exposure, suggests the occurrence of reinfection. The genomic surveillance of monkeypox virus, a better understanding of its interaction with the human host, and knowledge of the postinfection and postvaccine protection correlation are more relevant at this moment, when we observe an intersection of the mpox multicountry outbreak with the HIV/AIDS epidemic, considering the immunosenescence and other immune system issues caused by HIV.

Functionalization of calcium phosphates with biomimetic peptides is a promising strategy to increase cellular response for bone tissue repair. In this work, biphasic calcium phosphate pellets were functionalized with the hydroxyapatite-binding peptide pVTK by dropping a suspension of the peptide on the pellet surface. The bioactivity tests were performed in vitro by using McCoy culture medium. Cytotoxicity tests were also performed to assess cell viability. The material was characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy with field emission gun (FEG-SEM). The results showed that functionalization with the biomimetic peptide was most effective in inducing precipitation of bone-like apatite on the pellets surface, when compared to the control groups (two positive control groups and one negative control group). Cytotoxicity tests showed that all samples are biocompatible but the pellets with peptide showed the highest values of cell viability., Competing Interests: Declaration of competing interest I hereby declare that there is no financial interest involved in the submission of the study entitled “Biomineralization of Calcium Phosphates Functionalized with Hydroxyapatite-Binding Peptide”., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objectives: The impact of Covid-19 infection on pregnancy and perinatal outcomes is not fully known. To describe the risk factors and perinatal outcome of pregnant women with suspected COVID-19 infection., Methods: We evaluated medical records of women with suspected or confirmed SARS-CoV-2 infection who received health care services at the University Hospital of São Bernardo do Campo from March 1 to July 31, 2020, and personal, clinical, and laboratory data of these women and their newborns., Results: Of the 219 women identified, 29% were asymptomatic. Considering the total population, 26% and 17% had obesity and hypertensive syndrome, respectively. Fever measured in the emergency room was the main reason for hospitalization. The presence or not of flu-like symptoms did not impact on perinatal outcomes. Pregnant women requiring hospitalization had newborns with lower birth weight (p < 0.01), shorter length (p = 0.02), and smaller head circumference (p = 0.03), and, in these cases, a higher number of cesarean section deliveries was observed., Conclusion: COVID-19 infection did not affect the prognosis of pregnancy and newborns. However, the worst clinical outcome, requiring hospitalization, had an impact on the anthropometric measurements of newborns., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

In vitro maturation (IVM) is one of the most important steps in in vitro embryo production (IVEP). It is a complicated procedure in which nuclear and cytoplasmatic changes in oocytes appear. In order to carry out the in vitro maturation procedure correctly, it is necessary to provide the oocytes with as close to a natural (in vivo) environment as possible. Many factors contribute to the overall poor quality of in vitro-matured oocytes. One important factor may be oxidative stress (OS). The generation of oxidants, such as reactive oxygen species, is common under culture conditions. The solution for OC treatment and prevention is antioxidants. In the last 5 years, many studies have examined different antioxidants and their effects on in vitro maturation of oocytes and embryo production. The aim of this systematic review was to present the achievements of scientific research in the last five years, in which the effects of many antioxidants were tested on bovine oocyte maturation and embryo production.

Purpose: To determine the epidemiological profile of women who inserted copper intrauterine device (Cu-IUD), subdermal etonogestrel implant (ENG), tubal ligation (TL), depot medroxyprogesterone acetate (DMPA) or did not choose a contraceptive method (NCM) in the immediate postpartum period and compare the contraceptive effectiveness of Cu-IUD and DPMA with non-MAC., Methods: We analyzed the epidemiological profile of women who inserted copper intrauterine device (Cu-IUD), subdermal etonogestrel implant (ENG), tubal ligation (TL), depot medroxyprogesterone acetate (DMPA) or did not choose a contraceptive method (NCM) in the immediate postpartum. The data was collected by electronic medical records of postpartum women assisted at the University Hospital of São Bernardo do Campo (HMU-SBC) from January 2016 to December 2020. Also, we compared the contraceptive effectiveness of Cu-IUD and DPMA with non-MAC by identifying women who returned for second delivery during the study period and analyzing the contraceptive method chosen in the first hospitalization. Then the pregnancies interval and the sociodemographic characteristics were analyzed according to contraceptive method type., Results: Data from 20,896 women were collected, of which 8,183 (39%) opted for Cu-IUD, 559 (2.5%) DPMA, and 10,989 (52.5%) chose not to use contraception at the time of hospital discharge. When comparing these groups, women in the DPMA were younger (26.5 ± 7.3, p  < 0.05), and NCM showed women with a lower number of pregnancies (2.2 ± 1.3, p  < 0.05). Subjects in the TL group (4.6%) had the higher number of pregnancies (3.8 ± 1.2, p  < 0.05), and ENG group, the highest number of miscarriages (1.6 ± 1.3, p  < 0.05). Of those women who returned pregnant, 5.5% belonged to the DPMA group, 6% to the NCM group, and 2.3% to the Cu-IUD., Conclusions: Women who opted for Cu-IUD insertion were younger, had more pregnancies and vaginal delivery when compared to those who did not choose a method. Of those women who returned, the minority opted for Cu-IUD compared to those that opted for DPMA or no method., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Steiner, Mendes, Strufaldi, Carneiro, Giovanelli and da Silva.)

Background: Nutritional status and growth curves can affect cognitive development, increase the risk of infection, and contribute to the development of chronic diseases. Its etiology is related to food, socioeconomic, and maternal conditions. However, to date, no data on these parameters exist in the state of Goiás, Brazil., Objective: To compare the nutritional status and growth curves of children and adolescents in the city of Goiânia, Goiás, Brazil., Design and Setting: This was a cross-sectional study. A total of 529 individuals were recruited from a primary health center in the municipality., Methods: To assess nutritional status, the sample was divided into three categories: 3-4, 5-10, and 11-19 years, with z-score classification considering body mass index for age. The classification of growth curves was performed considering the median height values for age, assuming two references: (a) young Brazilian population and (b) one recommended for international use. The independent sample T-test was used to compare anthropometric variables., Results: The results showed that the classification of eutrophics represents a predominant percentage between both sexes (men: 03-04 = 55.4%; 05-10 = 57.6%; 11-19 = 53.5 % and women: 03-04 = 53.5%; 05-10 = 63.9%; 11-19 = 56.9%), and growth curves showed differences in specific periods in both sexes., Conclusions: It can be concluded that children and adolescents from the city of Goiânia present as predominance the eutrophic nutritional status, followed by the risk of overweight, underweight, obesity, and malnutrition of both sexes.

This study investigates the role of eugenol (EUG) on CS-induced acute lung injury (ALI) and how this compound is able to modulate macrophage activity. C57BL/6 mice were exposed to 12 cigarettes/day/5days and treated 15 min/day/5days with EUG. Rat alveolar macrophages (RAMs) were exposed to CSE (5%) and treated with EUG. In vivo, EUG reduced morphological changes inflammatory cells, oxidative stress markers, while, in vitro, it induced balance in the oxidative stress and reduced the pro-inflammatory cytokine release while increasing the anti-inflammatory one. These results suggest that eugenol reduced CS-induced ALI and acted as a modulator of macrophage activity.

Objectives: To describe the presence of anti-SARS-CoV-2 IgA and IgG in the blood and colostrum of women with COVID-19 infection during pregnancy and associate the presence of anti-SARS-CoV-2 IgA in colostrum with clinical symptoms of their newborns., Methods: A cross-sectional study was developed with 165 participants with COVID-19 infection during pregnancy and their newborns., Data Collected: characteristics COVID-19 infection in pregnant women, gestational age, and clinical symptoms in their newborns (fever, hypothermia, respiratory distress, hypotonia, hypoactivity, hypoglycemia, cyanosis, vomiting/regurgitation, abdominal distention, and jaundice). Maternal blood and colostrum samples were collected postpartum to to detect the presence of IgA and IgG anti-SARS-CoV-2., Results: The median interval between COVID-19 diagnosis and delivery was 37.5 days (IQ = 12.0, 73.0 days). Clinical symptoms during hospitalization were observed in 55 newborns (33.3%), and two (1.6%) tested RT-PCR positive for COVID-19. Positive colostrum for anti-SARS-CoV-2 IgA was found in 117 (70.9%) women. The presence of anti-SARS-CoV-2 IgA in colostrum was associated independently with lower clinical symptoms in their newborns (OR = 0.42; 95% CI 0.202 to 0.84; p = 0.015)., Conclusions for Practice: The presence of anti-SARS-CoV-2 IgA in colostrum was detected in more than two-thirds of the women evaluated and was associated with a lower frequency of clinical symptoms in their newborns., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The blood-brain barrier (BBB) is a tightly and actively regulated vascular barrier. Answering fundamental biological and translational questions about the BBB with currently available approaches is hampered by a trade-off between accessibility and biological validity. We report an approach combining micropipette-based local perfusion of capillaries in acute brain slices with multiphoton microscopy. Micro-perfusion offers control over the luminal solution and allows application of molecules and drug delivery systems, whereas the bath solution defines the extracellular milieu in the brain parenchyma. Here we show, that this combination allows monitoring of BBB transport at the cellular level, visualization of BBB permeation of cells and molecules in real-time and resolves subcellular details of the neurovascular unit. In combination with electrophysiology, it permits comparison of drug effects on neuronal activity following luminal versus parenchymal application. We further apply micro-perfusion to the human and mouse BBB of epileptic hippocampi highlighting its utility for translational research and analysis of therapeutic strategies., (© 2023. The Author(s).)

Maintaining an appropriate balance between excitation and inhibition is critical for neuronal information processing. Cortical neurons can cell-autonomously adjust the inhibition they receive to individual levels of excitatory input, but the underlying mechanisms are unclear. We describe that Ste20-like kinase (SLK) mediates cell-autonomous regulation of excitation-inhibition balance in the thalamocortical feedforward circuit, but not in the feedback circuit. This effect is due to regulation of inhibition originating from parvalbumin-expressing interneurons, while inhibition via somatostatin-expressing interneurons is unaffected. Computational modeling shows that this mechanism promotes stable excitatory-inhibitory ratios across pyramidal cells and ensures robust and sparse coding. Patch-clamp RNA sequencing yields genes differentially regulated by SLK knockdown, as well as genes associated with excitation-inhibition balance participating in transsynaptic communication and cytoskeletal dynamics. These data identify a mechanism for cell-autonomous regulation of a specific inhibitory circuit that is critical to ensure that a majority of cortical pyramidal cells participate in information coding., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Knowledge about viral characteristics, mechanisms of entry into the host cell and multiplication/dissemination can help in the control and treatment of viral pathologies. Several nutritional factors linked to the host may favour viral multiplication and their control, may lead to new prophylactic alternatives and/or antiviral therapies. The objective of this review is to discuss the relationship between the amino acid L-lysine and the control of viral infections, aiming at a possible therapeutic property. This research used databases such as PubMed, Web of Science, Scielo, Medline and Google Scholar, as well as searching for references cited by journals. The time frame covered the period between 1964 and January 2022. The observed studies have shown that the usual antiviral therapies are not able to interfere with the viruses in their latent state; however, they can interfere with the adhesion and fusion of viral particles or the production of proteins, which play an important role in viral epidemiology and control, particularly in the initial moment and in reactivation. Lysine is an amino acid that can interfere mainly in the formation of capsid proteins and DNA by a competitive antagonism with amino acid arginine, which is an essential amino acid for some viruses, and also by promoting the increase of arginase, increasing the catabolism of arginine. Although there is evidence of the importance of L-lysine in viral control, more studies are needed, with a view to new antiviral therapies., (© 2022 British Pharmacological Society.)

Alzheimer's disease (AD) is characterized by progressive, irreversible loss of memory and cognitive function. Drosophila melanogaster and other animal models are used to study several diseases, in order to elucidate unknown mechanisms and develop potential therapies. Molecular studies require biological samples and, for neuropathologies such as AD biopsy of the human brain, are invasive and potentially damaging. The solution is to use animal models, such as D. melanogaster, which is a model organism that can replace mammalian organisms in such studies. In this study, we evaluated the climbing ability and differential gene expression during AD progression due to the amylodoigenic pathway using RNA-seq, and we performed an in silico analysis of a fruit fly AD-like GFP (Green Fluorescent Protein) model with GFP expression in the pan-neural elav driver. A total of 1388 genes were differentially expressed in all analyzed groups. The main pathways related to those Differentially Expressed Genes (DEGs) during aging and AD progression were evaluated using the fly genes and human orthologs, in order to link genomic information to higher-order functional information with gene pathway mapping. We identified pathways present in all analyzed groups, such as metabolic pathways, ribosomal pathways, proteasome pathways and immune system pathways. Some of the genes were validated by qPCR. Knockdown of CG17754 gene by RNAi promoted degeneration in the fly eye, validating these findings in vivo. The identification of similarities in molecular pathways between the transgenic fly AD-like GFP model and mammals related to AD provides new insights into the use of this fly in screening novel anti-AD drugs., (Copyright © 2022 Japan Neuroscience Society and Elsevier B.V. All rights reserved.)

Alzheimer's disease (AD) is the most common form of dementia in the elderly, affecting cognitive, intellectual, and motor functions. Different hypotheses explain AD's mechanism, such as the amyloidogenic hypothesis. Moreover, this disease is multifactorial, and several studies have shown that gut dysbiosis and oxidative stress influence its pathogenesis. Knowing that kefir is a probiotic used in therapies to restore dysbiosis and that the bioactive peptides present in it have antioxidant properties, we explored its biotechnological potential as a source of molecules capable of modulating the amyloidogenic pathway and reducing oxidative stress, contributing to the treatment of AD. For that, we used Drosophila melanogaster model for AD (AD-like flies). Identification of bioactive peptides in the kefir sample was made by proteomic and peptidomic analyses, followed by in vitro evaluation of antioxidant and acetylcholinesterase inhibition potential. Flies were treated and their motor performance, brain morphology, and oxidative stress evaluated. Finally, we performed molecular docking between the peptides found and the main pathology-related proteins in the flies. The results showed that the fraction with the higher peptide concentration was positive for the parameters evaluated. In conclusion, these results revealed these kefir peptide-rich fractions have therapeutic potential for AD., (© 2022. The Author(s).)

The aim of this study was to compare two different maximal intensity exercise modality training protocols of similar durations on muscle strength, cardiorespiratory fitness, and lower limb composition in recreationally trained men. Twenty-five trained men (28.9 ± 5.6 years) were randomly divided into Cycle ergometer (4 sets of 30 seconds sprints) and Leg press (4 sets of 10-12 repetitions to momentary failure). Both groups trained three times a week for 5 weeks. Before and after the training period, the participants performed a 10-repetition maximum (10RM) test for knee extension, an incremental exercise test on a treadmill for time to exhaustion (TTE) and peak oxygen consumption ( V ˙ O 2peak ) and underwent dual energy X-ray absorptiometry to assess lower limb composition. Knee extension 10RM and TTE increased in both groups with no statistically significant between group ( p = 0.614 and p = 0.210). Only cycle ergometer group increased V ˙ O 2peak ( p = 0,012). For all lower limb composition outcomes, changes were minimal. The results suggest that 5 weeks of effort and duration matched exercise protocols using cycle ergometer training or leg press may produce similar strength adaptations.