Ambient oxygen levels regulate intestinal dysbiosis and GVHD severity after allogeneic stem cell transplantation.

The severity of T cell-mediated gastrointestinal (GI) diseases such as graft-versus-host disease (GVHD) and inflammatory bowel diseases correlates with a decrease in the diversity of the host gut microbiome composition characterized by loss of obligate anaerobic commensals. The mechanisms underpinning these changes in the microbial structure remain unknown. Here, we show in multiple specific pathogen-free (SPF), gnotobiotic, and germ-free murine models of GI GVHD that the initiation of the intestinal damage by the pathogenic T cells altered ambient oxygen levels in the GI tract and caused dysbiosis. The change in oxygen levels contributed to the severity of intestinal pathology in a host intestinal HIF-1α- and a microbiome-dependent manner. Regulation of intestinal ambient oxygen levels with oral iron chelation mitigated dysbiosis and reduced the severity of the GI GVHD. Thus, targeting ambient intestinal oxygen levels may represent a novel, non-immunosuppressive strategy to mitigate T cell-driven intestinal diseases.

Ancient DNA at the edge of the world: Continental immigration and the persistence of Neolithic male lineages in Bronze Age Orkney.

Orkney was a major cultural center during the Neolithic, 3800 to 2500 BC. Farming flourished, permanent stone settlements and chambered tombs were constructed, and long-range contacts were sustained. From ∼3200 BC, the number, density, and extravagance of settlements increased, and new ceremonial monuments and ceramic styles, possibly originating in Orkney, spread across Britain and Ireland. By ∼2800 BC, this phenomenon was waning, although Neolithic traditions persisted to at least 2500 BC. Unlike elsewhere in Britain, there is little material evidence to suggest a Beaker presence, suggesting that Orkney may have developed along an insular trajectory during the second millennium BC. We tested this by comparing new genomic evidence from 22 Bronze Age and 3 Iron Age burials in northwest Orkney with Neolithic burials from across the archipelago. We identified signals of inward migration on a scale unsuspected from the archaeological record: As elsewhere in Bronze Age Britain, much of the population displayed significant genome-wide ancestry deriving ultimately from the Pontic-Caspian Steppe. However, uniquely in northern and central Europe, most of the male lineages were inherited from the local Neolithic. This suggests that some male descendants of Neolithic Orkney may have remained distinct well into the Bronze Age, although there are signs that this had dwindled by the Iron Age. Furthermore, although the majority of mitochondrial DNA lineages evidently arrived afresh with the Bronze Age, we also find evidence for continuity in the female line of descent from Mesolithic Britain into the Bronze Age and even to the present day.

Preservation of the fecal microbiome is associated with reduced severity of graft-versus-host disease.

Following allogeneic hematopoietic cell transplantation (allo-HCT), the gastrointestinal (GI) tract is frequently affected by acute graft-versus-host disease (aGVHD), the pathophysiology of which is associated with a dysbiotic microbiome. Since microbial composition varies along the length of the GI tract, the authors hypothesized that microbiome features correlate with the pattern of organ involvement after allo-HCT. We evaluated 266 allo-HCT recipients from whom 1303 stool samples were profiled by 16S ribosomal gene sequencing. Patients were classified according to which organs were affected by aGVHD. In the 20 days prior to disease onset, GVHD patients had lower abundances of members of the class Clostridia, lower counts of butyrate producers, and lower ratios of strict-to-facultative (S/F) anaerobic bacteria compared with allograft recipients who were free of GVHD. GI GVHD patients showed significant reduction in microbial diversity preonset. Patients with lower GI aGVHD had lower S/F anaerobe ratios compared with those with isolated upper GI aGVHD. In the 20 days after disease onset, dysbiosis was observed only in GVHD patients with GI involvement, particularly those with lower-tract disease. Importantly, Clostridial and butyrate-producer abundance as well as S/F anaerobe ratio were predictors of longer overall survival; higher abundance of butyrate producers and higher S/F anaerobe ratio were associated with decreased risk of GVHD-related death. These findings suggest that the intestinal microbiome can serve as a biomarker for outcomes of allo-HCT patients with GVHD.

Early intestinal microbial features are associated with CD4 T-cell recovery after allogeneic hematopoietic transplant.

Low intestinal microbial diversity is associated with poor outcomes after allogeneic hematopoietic cell transplantation (HCT). Using 16S rRNA sequencing of 2067 stool samples and flow cytometry data from 2370 peripheral blood samples drawn from 894 patients who underwent allogeneic HCT, we have linked features of the early post-HCT microbiome with subsequent immune cell recovery. We examined lymphocyte recovery and microbiota features in recipients of both unmodified and CD34-selected allografts. We observed that fecal microbial diversity was an independent predictor of CD4 T-cell count 3 months after HCT in recipients of a CD34-selected allograft, who are dependent on de novo lymphopoiesis for their immune recovery. In multivariate models using clinical factors and microbiota features, we consistently observed that increased fecal relative abundance of genus Staphylococcus during the early posttransplant period was associated with worse CD4 T-cell recovery. Our observations suggest that the intestinal bacteria, or the factors they produce, can affect early lymphopoiesis and the homeostasis of allograft-derived T cells after transplantation.

Alloreactive T cells deficient of the short-chain fatty acid receptor GPR109A induce less graft-versus-host disease.

The intestinal microbiota is essential for the fermentation of dietary fiber into short-chain fatty acids (SCFA) such as butyrate, acetate, and propionate. SCFAs can bind to the G-protein-coupled receptors GPR43 and GPR109A (HCAR2), with varying affinities to promote cellular effects in metabolism or changes in immune function. We explored the role of GPR109A as the main receptor for butyrate in mouse models of allogeneic hematopoietic cell transplantation (allo-HCT) and graft-versus-host disease (GVHD). Deletion of GPR109A in allo-HCT recipients did not affect GVHD, but transplantation of T cells from GPR109A knockout (KO) (Gpr109a-/-) mice into allo-HCT recipient mice significantly reduced GVHD morbidity and mortality compared with recipients of wild-type (WT) T cells. Recipients of Gpr109a-/- T cells exhibited less GVHD-associated target organ pathology and decreased proliferation and homing of alloreactive T cells to target tissues. Although Gpr109a-/- T cells did not exhibit immune deficits at a steady state, following allo-activation, Gpr109a-/- T cells underwent increased apoptosis and were impaired mitochondrial oxidative phosphorylation, which was reversible through antioxidant treatment with N-acetylcysteine (NAC). In conclusion, we found that GPR109A expression by allo-activated T cells is essential for metabolic homeostasis and expansion, which are necessary features to induce GVHD after allo-HCT.

Upregulation of the canonical signaling pathway of interferon-gamma is associated with glioblastoma progression.

BACKGROUND: Glioblastoma is a brain malignant tumor grade IV, highly invasive. Alterations in several signaling pathways are involved in glioblastoma development. In this work, we evaluated the IFN-γ canonical signaling pathway in glioblastoma cells and its effect on cell viability and migration. METHODS: The levels of STAT1/pSTAT1, IRF1, and PD-L1 in LN-18 glioblastoma cells were analyzed using western blotting. Cell viability was evaluated by calcein-AM/propidium iodide assays, and a wound healing assay was used to study the migration of glioblastoma cells treated with IFN-γ. Our aim was to determine the expression of IFN-γ signaling elements in cell lines and tissue from glioblastoma samples and examine the relationship between these elements and the survival of glioblastoma patients. The following platforms were utilized for analysis: the CCLE (Cancer Cell Line Encyclopedia), UALCAN (University of Alabama at Birmingham Cancer data analysis Portal), GEPIA (Gene Expression Profiling Interactive Analysis), and GENT2 (Gene Expression patterns across Normal and Tumor tissues). RESULTS: Our results evidenced that IFN-γ signaling increases non-phosphorylated and phosphorylated STAT1 levels and promotes the upregulation of IRF1 and PD-L1 in glioblastoma cells. The activation of IFN-γ signaling increased cell migration without affecting the viability of glioblastoma cells. Furthermore, in silico analysis showed that the elements of IFN-γ signaling pathways (IFNGR1/IFNGR2/STAT1/IRF1) are upregulated in human glioblastoma samples. The upregulation of IFN-γ signaling was associated with shorter survival in glioblastoma patients. CONCLUSION: IFN-γ signaling pathway is upregulated in glioblastoma, displaying pro-tumor activity. Thus, IFN-γ signaling elements may be potential biomarkers and targets for treating glioblastoma.

Effective adsorption of cadmium and nickel ions in mono and bicomponent systems using eco-friendly adsorbents prepared from peanut shells.

The work investigates the potential of peanut shells, an abundant agro-industrial waste, to serve as an adsorbent precursor for the effective and simple treatment of effluents loaded with cadmium and nickel ions. Among the adsorbents prepared, carbonized peanut shell (CCarb), due to its higher adsorption capacity, proved to be the most effective compared to carbonized and activated peanut shell (CATQ). The carbonization process led to structural changes, which resulted in an increase in surface area (around 6 times more in CATQ) and pore volume (around 3 times more in CATQ). Even so, the amount of H+ acid sites due to acid activation produced unfavorable effects for adsorption. Hydroxyl, carboxyl and carbonyl groups were identified on the adsorbent surface which presented favorable charges for metal adsorption. This improvement propels the carbonized variant to the forefront, demonstrating the highest adsorption capacity and reaching equilibrium in less than 90 and 60 min for cadmium and nickel ions, respectively. In both monocomponent and bicomponent systems concentrations greater than 40 ppm signify an increase in adsorption capacity for Ni2+. The experimental data best fit the Freundlich model, showing maximum adsorption capacities of 17.04 mg g-1 for cadmium and 31.28 mg g-1 for nickel. Despite the antagonistic effect observed in the bicomponent system, this study concludes by underlining the promise of activated carbon from peanut shells to harmonize technical and environmental concerns.

Nutritional strategies cause memory damage and alter biochemical parameters without causing neuroinflammation.

Obesity results from an energy imbalance and has been considered an epidemic due to its increasing rates worldwide. It is classified as a low-grade chronic inflammatory disease and has associated comorbidities. Different nutritional strategies are used for the purpose of weight loss, highlighting low-carbohydrate (LC) diets, ketogenic diets, and intermittent fasting (IF). These strategies can lead to metabolic and behavioral changes as they stimulate different biochemical pathways. Therefore, this study evaluated memory, energy metabolism, neuroinflammation, oxidative stress, and antioxidant defense parameters in mice subjected to an LC diet, ketogenic diet (KD), or IF. Eighty male Swiss mice, 60 days old, were divided into 4 groups: control, LC, KD, or IF. Body weight was measured weekly, and food intake every 48 h. After 15 days of nutritional interventions, the animals were subjected to the behavioral object recognition test and subsequently euthanized. Then, visceral fat was removed and weighed, and the brain was isolated for inflammatory and biochemical analysis. We concluded from this study that the LC and KD strategies could damage memory, IF improves the production of adenosine triphosphate (ATP), and the LC, KD, and IF strategies do not lead to neuroinflammatory damage but present damage at the level of oxidative stress.

Annexin A1 attenuates cardiac diastolic dysfunction in mice with inflammatory arthritis.

Rheumatoid arthritis (RA) carries a twofold increased incidence of heart failure with preserved ejection fraction, accompanied by diastolic dysfunction, which can lead to death. The causes of diastolic dysfunction are unknown, and there are currently no well-characterized animal models for studying these mechanisms. Current medications for RA do not have marked beneficial cardio-protective effects. K/BxN F1 progeny and KRN control mice were analyzed over time for arthritis development, monitoring left ventricular diastolic and systolic function using echocardiography. Excised hearts were analyzed by flow cytometry, qPCR, and histology. In pharmacological experiments, K/BxN F1 mice were treated with human recombinant AnxA1 (hrAnxA1, 1 µg/mouse) or vehicle daily. K/BxN F1 mice exhibited fully developed arthritis with normal cardiac function at 4 wk; however, by week 8, all mice displayed left ventricular diastolic dysfunction with preserved ejection fraction. This dysfunction was associated with cardiac hypertrophy, myocardial inflammation and fibrosis, and inflammatory markers. Daily treatment of K/BxN F1 mice with hrAnxA1 from weeks 4 to 8 halted progression of the diastolic dysfunction. The treatment reduced cardiac transcripts of proinflammatory cytokines and profibrotic markers. At the cellular level, hrAnxA1 decreased activated T cells and increased MHC IIlow macrophage infiltration in K/BxN F1 hearts. Similar effects were obtained when hrAnxA1 was administered from week 8 to week 15. We describe an animal model of inflammatory arthritis that recapitulates the cardiomyopathy of RA. Treatment with hrAnxA1 after disease onset corrected the diastolic dysfunction through modulation of both fibroblast and inflammatory cell phenotype within the heart.

Epidemiological profile of luxations injuries with or without dental fractures in permanent teeth: A 10-years retrospective study.

BACKGROUND/AIM: This study assessed the epidemiology of luxation injuries with or without dental fractures in patients attending the outpatient clinic of a Brazilian dental school over the past decade. MATERIAL AND METHODS: We reviewed clinical records from a specialized center for dental trauma care in Brazil, focusing on patients who experienced at least one traumatic dental injury (TDI) in a permanent tooth between 2012 and 2022. The extracted data included sex, age, etiology, time between trauma occurrence and the search for initial care, TDI classification, and the need for endodontic treatment. The statistical analysis involved Pearson's chi-squared and Fisher's exact tests at a 5% significance level. RESULTS: The 366 analyzed clinical records included 166 patients (350 teeth) with luxation injuries. Men (n = 102) showed a higher prevalence of luxation injuries than women (n = 64). Extrusive luxation prevailed (n = 99 patients and 208 teeth). Patients with luxation injuries sought care promptly after dental trauma incidents (p = .02) and demonstrated a higher incidence of endodontic treatment (p < .0001) than those without luxation injuries. Lateral luxation was notably associated with traffic accidents (p < .0001). The combination of luxation injuries and tooth fractures did not correlate with a higher need for endodontic treatment (p > .05). CONCLUSIONS: Age and trauma etiology seemed to have influenced the epidemiological profile of luxation injuries. Additionally, these injuries affected the time to seek initial care and the need for endodontic treatment.

Improved nasal trumpet: "In-house" device to promote the healing of skin grafts in the anterior nasal nostril.

This technical note addresses the complexities of reconstructive surgery for malignant skin lesions in the lower nasal aperture and pericolumellar region. Traditional solutions, such as free skin grafts, face challenges in maintaining attachment to the surgical site without adequate support. Nasal packing, a common approach, obstructs the nasal opening and compromises air passage, hindering ventilation. The use of a nasal trumpet has proven beneficial in maintaining nasal patency in various cases, but it falls short of addressing the specific challenges posed by reconstructive surgery. The proposed solution involves a novel device comprising a nasal cannula, surgical sponge, and fine mesh gauze with 3% bismuth tribromophenate. This combination serves a triple purpose: the nasal cannula facilitates air passage, the surgical sponge applies controlled pressure around the nasal opening to aid graft adhesion, and the gauze with bismuth tribromophenate promotes wound healing and prevents infection. The assembled device is inserted into the nostril, anchored to the patient's skin with silk stitches. This innovative approach offers a practical solution for maintaining nasal patency, promoting graft adherence, and supporting wound healing in reconstructive surgery.

Microbiota as Predictor of Mortality in Allogeneic Hematopoietic-Cell Transplantation.

BACKGROUND: Relationships between microbiota composition and clinical outcomes after allogeneic hematopoietic-cell transplantation have been described in single-center studies. Geographic variations in the composition of human microbial communities and differences in clinical practices across institutions raise the question of whether these associations are generalizable. METHODS: The microbiota composition of fecal samples obtained from patients who were undergoing allogeneic hematopoietic-cell transplantation at four centers was profiled by means of 16S ribosomal RNA gene sequencing. In an observational study, we examined associations between microbiota diversity and mortality using Cox proportional-hazards analysis. For stratification of the cohorts into higher- and lower-diversity groups, the median diversity value that was observed at the study center in New York was used. In the analysis of independent cohorts, the New York center was cohort 1, and three centers in Germany, Japan, and North Carolina composed cohort 2. Cohort 1 and subgroups within it were analyzed for additional outcomes, including transplantation-related death. RESULTS: We profiled 8767 fecal samples obtained from 1362 patients undergoing allogeneic hematopoietic-cell transplantation at the four centers. We observed patterns of microbiota disruption characterized by loss of diversity and domination by single taxa. Higher diversity of intestinal microbiota was associated with a lower risk of death in independent cohorts (cohort 1: 104 deaths among 354 patients in the higher-diversity group vs. 136 deaths among 350 patients in the lower-diversity group; adjusted hazard ratio, 0.71; 95% confidence interval [CI], 0.55 to 0.92; cohort 2: 18 deaths among 87 patients in the higher-diversity group vs. 35 deaths among 92 patients in the lower-diversity group; adjusted hazard ratio, 0.49; 95% CI, 0.27 to 0.90). Subgroup analyses identified an association between lower intestinal diversity and higher risks of transplantation-related death and death attributable to graft-versus-host disease. Baseline samples obtained before transplantation already showed evidence of microbiome disruption, and lower diversity before transplantation was associated with poor survival. CONCLUSIONS: Patterns of microbiota disruption during allogeneic hematopoietic-cell transplantation were similar across transplantation centers and geographic locations; patterns were characterized by loss of diversity and domination by single taxa. Higher diversity of intestinal microbiota at the time of neutrophil engraftment was associated with lower mortality. (Funded by the National Cancer Institute and others.).

Impact of the COVID-19 pandemic on the mental health of frontline healthcare workers in a highly affected region in Brazil.

BACKGROUND: The COVID-19 pandemic had a major impact on the mental health of healthcare workers (HCWs), especially in low and middle-income countries, which had to face additional political, social, and economic challenges. We thus aimed to assess the prevalence of mental health outcomes and the associated factors in HCWs treating COVID-19 patients in one of the most affected regions in Brazil. METHODS: We used the Respondent-Driven Sampling method to assess the risks of COVID-19 infection and symptoms of mental disorders in nurses, nursing technicians, and physicians who worked on the frontline in the metropolitan region of Recife. 865 healthcare workers completed a survey regarding sociodemographic data, work-related risks, and symptoms of mental disorders - SRQ-20 for common mental disorders (CMD); AUDIT-C for problematic alcohol use; GAD-7 for anxiety; PHQ-9 for depression; PCL-5 for post-traumatic stress disorder (PTSD). Gile's successive sampling estimator was used to produce the weighted estimates by professional category. A Poisson regression model with robust variance was used to analyze factors associated with a positive screening for CMD. We will present the results of a cross-sectional analysis of the mental health outcomes after the first peak of COVID-19 - from August 2020 to February 2021. RESULTS: The prevalence ratios for a positive screening for CMD were 34.9% (95% CI: 27.8-41.9) in nurses, 28.6% (95% CI: 21.3-36.0) in physicians, and 26.6% (95% CI: 16.8-36.5) in nursing technicians. Nurses presented a higher prevalence of depressive symptoms (23%). Positive screening for problematic alcohol use (10.5 to14.0%), anxiety (10.4 to 13.3%), and PTSD (3.3 to 4.4%) were similar between the professional categories. The main factors associated with CMD in nurses and physicians were related to an intrinsic susceptibility to mental illness, such as previous or family history of psychiatric disorder, and female sex. Among nurse technicians, work-related factors, such as accidents with biological material, presented the strongest association with CMD. CONCLUSION: The mental health of HCWs fighting COVID-19 in Recife was severely affected. It is crucial that healthcare services provide adequate working conditions and psychological support, investing in programs to promote and protect HCWs mental health.

Summary of the first Brazilian Symposium on Human Biometeorology.

This brief background highlights Brazil as a 'climate-health hotspot', i.e. a country where climate affects local populations negatively through multiple pathways (Di Napoli et al. BMC Public Health 22(1):1-8, 2022). Knowledge gaps still need to be filled concerning the various climaterelated dimensions of tourism, vector-borne diseases, mortality and morbidity in urban centers in the country (Krüger et al. Int J Biometeorol 66(7):1297-1315, 2022). Motivated by this, the first Brazilian Symposium on Human Biometeorology (Simpósio Brasileiro de Biometeorologia Humana 2022) was organized and held at the Federal University of Rio Grande do Norte (UFRN) in Natal, northeastern Brazil, between July 4 and 8, 2022. The symposium was organized as a hybrid event by a committee composed of researchers acting in different regions of the country, and who had an ongoing research collaboration on matters related to human biometeorology. The event was partly sponsored by the ISB and partly self-supported by the organizers and institutions involved. The symposium aimed to promote the development of the research area on human biometeorology in Brazil in facing challenges imposed by a globally and locally changing climate. To achieve this, the symposium focused on five main topics of discussion: a) climate-driven diseases; b) thermal comfort, urban and architectural biometeorology; c) atmospheric pollution and health; d) climate change; e) climate, health and climate change. This summary highlights the main findings, future research directions, and policy implications in each topic from the presentations and panel discussions.

Canonical Wnt Pathway Is Involved in Chemoresistance and Cell Cycle Arrest Induction in Colon Cancer Cell Line Spheroids.

The presence of cancer stem cells (CSCs) has been associated with the induction of drug resistance and disease recurrence after therapy. 5-Fluorouracil (5FU) is widely used as the first-line treatment of colorectal cancer (CRC). However, its effectiveness may be limited by the induction of drug resistance in tumor cells. The Wnt pathway plays a key role in the development and CRC progression, but it is not clearly established how it is involved in CSCs resistance to treatment. This work aimed to investigate the role played by the canonical Wnt/ß-catenin pathway in CSCs resistance to 5FU treatment. Using tumor spheroids as a model of CSCs enrichment of CRC cell lines with different Wnt/ß-catenin contexts, we found that 5FU induces in all CRC spheroids tested cell death, DNA damage, and quiescence, but in different proportions for each one: RKO spheroids were very sensitive to 5FU, while SW480 were less susceptible, and the SW620 spheroids, the metastatic derivative of SW480 cells, displayed the highest resistance to death, high clonogenic capacity, and the highest ability for regrowth after 5FU treatment. Activating the canonical Wnt pathway with Wnt3a in RKO spheroids decreased the 5FU-induced cell death. But the Wnt/ß-catenin pathway inhibition with Adavivint alone or in combination with 5FU in spheroids with aberrant activation of this pathway produced a severe cytostatic effect compromising their clonogenic capacity and diminishing the stem cell markers expression. Remarkably, this combined treatment also induced the survival of a small cell subpopulation that could exit the arrest, recover SOX2 levels, and re-grow after treatment.

Lysophosphatidylinositol Promotes Chemotaxis and Cytokine Synthesis in Mast Cells with Differential Participation of GPR55 and CB2 Receptors.

Mast cells (MCs) are the main participants in the control of immune reactions associated with inflammation, allergies, defense against pathogens, and tumor growth. Bioactive lipids are lipophilic compounds able to modulate MC activation. Here, we explored some of the effects of the bioactive lipid lysophosphatidylinositol (LPI) on MCs. Utilizing murine bone marrow-derived mast cells (BMMCs), we found that LPI did not cause degranulation, but slightly increased FcεRI-dependent ß-hexosaminidase release. However, LPI induced strong chemotaxis together with changes in LIM kinase (LIMK) and cofilin phosphorylation. LPI also promoted modifications to actin cytoskeleton dynamics that were detected by an increase in cell size and interruptions in the continuity of the cortical actin ring. The chemotaxis and cortical actin ring changes were dependent on GPR55 receptor activation, since the specific agonist O1602 mimicked the effects of LPI and the selective antagonist ML193 prevented them. The LPI and O1602-dependent stimulation of BMMC also led to VEGF, TNF, IL-1α, and IL-1ß mRNA accumulation, but, in contrast with chemotaxis-related processes, the effects on cytokine transcription were dependent on GPR55 and cannabinoid (CB) 2 receptors, since they were sensitive to ML193 and to the specific CB2 receptor antagonist AM630. Remarkably, GPR55-dependent BMMC chemotaxis was observed towards conditioned media from distinct mouse and human cancer cells. Our data suggest that LPI induces the chemotaxis of MCs and leads to cytokine production in MC in vitro with the differential participation of GPR55 and CB2 receptors. These effects could play a significant role in the recruitment of MCs to tumors and the production of MC-derived pro-angiogenic factors in the tumor microenvironment.

Can Epigenetics Help Solve the Puzzle Between Concomitant Cardiovascular Injury and Severity of Coronavirus Disease 2019?

ABSTRACT: The ongoing coronavirus disease 2019 (COVID-19) pandemic caused by SARS-CoV-2 has significant implications in patients with concomitant cardiovascular disease (CVD) because they are the population at the greatest risk of death. The treatment of such patients and complications may represent a new challenge for the fields of cardiology and pharmacology. Thus, understanding the involvement of this viral infection in CVD might help to reduce the aggressiveness of SARS-CoV-2 in causing multiorgan infection and damage. SARS-CoV-2 disturbs the host epigenome and several epigenetic processes involved in the pathophysiology of COVID-19 that can directly affect the function and structure of the cardiovascular system (CVS). Hence, it would be relevant to identify epigenetic alterations that directly impact CVS physiology after SARS-CoV-2 infection. This could contribute to the view of this virus-induced CVS injury and direct forthcoming tackles for COVID-19 treatment to reduce mortality in patients with CVD. Targeting epigenetic marks could offer strong evidence for the development of novel antiviral therapies, especially in the context of COVID-19-related CVS damage. In this review, we address some of the main signaling pathways that are currently known as being involved in COVID-19 pathophysiology and the importance of this glint on epigenetics and some of its modifiers (epidrugs) to control the unregulated epitope activity in the context of SARS-CoV-2 infection, COVID-19, and underlying CVD.

PROPER-PRehabilitatiOn Plus Enhanced Recovery after surgery versus enhanced recovery after surgery in gynecologic oncology: a randomized clinical trial.

BACKGROUND: Prehabilitation is a process that occurs before surgery and aims to improve patient functional capacity and enhance surgical recovery. This process includes medical, nutritional, physical, and psychological interventions that may reduce the duration of hospital stay and provide postoperative physical benefits. PRIMARY OBJECTIVE: To evaluate the impact of a prehabilitation program on postoperative recovery time for patients who will undergo gynecological surgery following the Enhanced Recovery After Surgery (ERAS) guidelines. STUDY HYPOTHESIS: A multidisciplinary, preoperative prehabilitation program for patients who will undergo gynecological surgery leads to a reduction in the length of hospital stay and improves patient functional capacity. TRIAL DESIGN: Prospective, interventionist, and randomized controlled trial in a 1:1 ratio, open to multidisciplinary team and patients, blinded to surgeons and anesthesiologists. The control group will undergo ERAS standard preoperative care while the intervention group will have ERAS standard preoperative care plus prehabilitation. MAJOR INCLUSION CRITERIA: Patients scheduled to undergo gynecologic surgery performed by laparotomy with a preoperative schedule that allows prehabilitation intervention for 2 to 3 weeks. PRIMARY ENDPOINT: To compare time between surgery and the day the patient is ready for discharge in patients who underwent the prehabilitation process versus those who did not. Readiness for discharge is defined as the ability to take care of one's-self, to walk alone, and to ingest at least 75% of daily recommended calorie intake. SAMPLE SIZE: 194 participants ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: At present, 30 patients have been recruited. Accrual should be completed by 2023-24. TRIAL REGISTRATION: The study is approved by the IBCC - São Camilo Oncologia ethics committee (reference number 4.256.553) and is registered at clinicaltrials.gov (NCT04596800).

A first approach to human biometeorology research in Brazil: a systematic review and meta-analysis.

This systematic review aims to give an overview of the diversity of research areas related to human biometeorology in Brazil. The main focus of this paper addresses research trends, represented by published papers with national and international authorship, main contributions and shortcomings, as well as challenges and prospects of research in this area of study. An extensive literature search was conducted in the Scopus, Web of Science, and Science Direct databases so as to identify relevant publication output up to July 2021 related to the research area. The screening resulted in 96 studies chosen for full-text reading. Overall, results indicated a reduced amount of articles on the subject matter published internationally, with noticeable gaps in research in some regions of the country, such as the Amazon region and in the Brazilian Midwest region. Research gaps in relevant areas have been identified with limited output in the climate dimensions of tourism, vector-borne diseases, mortality and morbidity in urban centers. Such gaps should further encourage researchers to engage in research focused on those areas.

Effect of Nellore (Bos indicus) donor age on in-vitro embryo production and pregnancy rate.

The aim of this study was to evaluate the effect of age of Nellore (Bos indicus) donors on the efficiency of in vitro embryo production (IVEP) and pregnancy rate. Thirty-six donors, including 11 female calves (13 ± 0.61 months), 17 prepubertal heifers (25 ± 0.78 months) and 8 cows (83 ± 28 months), were submitted to 3 procedures of ovum pickup (OPU) on random days of the estrous cycle at intervals of 21 days. Caspase-3 and IGFBP2 were quantified in oocytes and blastocysts for the evaluation of oocyte and embryo quality. The produced embryos were vitrified (n = 445) and transferred to synchronized recipients. Cows produced a larger number of follicles (cows: 54.5 ± 6.2; calves: 20.0 ± 0.57; prepubertal heifers: 20.8 ± 0.46), total oocytes (cows: 45.97 ± 7.22; calves: 28.93 ± 6.14; prepubertal heifers: 27.21 ± 4.94) and cleaved oocytes (cows: 21.14 ± 4.22; calves: 13.09 ± 3.72; prepubertal heifers: 12.4 ± 3.19). The cleavage rate was similar between age categories; however, cows tended (p < 0.07) to produce a larger number of blastocysts (9.74 ± 2.26) per OPU than calves (5.57 ± 1.99) and prepubertal heifers tended to have a higher blastocyst yield (35.4%) than calves (27.1%) (p < .07). The expression levels of IGFBP2 and caspase-3 were higher in oocytes derived from calves compared to the other two categories. The pregnancy rate was higher in calves (43.1%) and cows (40.4%) than in prepubertal heifers (33.8%) (p = .03). Despite the larger numbers of follicles and viable oocytes in cows, the blastocyst production results and pregnancy rates obtained indicate that the use of young females as oocyte donors in IVEP is feasible and may contribute to reduce the generation interval.