Low-pass whole genome sequencing as a cost-effective alternative to chromosomal microarray analysis for low- and middle-income countries.

Low-pass whole genome sequencing (LP-WGS) has been applied as alternative method to detect copy number variants (CNVs) in the clinical setting. Compared with chromosomal microarray analysis (CMA), the sequencing-based approach provides a similar resolution of CNV detection at a lower cost. In this study, we assessed the efficiency and reliability of LP-WGS as a more affordable alternative to CMA. A total of 1363 patients with unexplained neurodevelopmental delay/intellectual disability, autism spectrum disorders, and/or multiple congenital anomalies were enrolled. Those patients were referred from 15 nonprofit organizations and university centers located in different states in Brazil. The analysis of LP-WGS at 1x coverage (>50kb) revealed a positive testing result in 22% of the cases (304/1363), in which 219 and 85 correspond to pathogenic/likely pathogenic (P/LP) CNVs and variants of uncertain significance (VUS), respectively. The 16% (219/1363) diagnostic yield observed in our cohort is comparable to the 15%-20% reported for CMA in the literature. The use of commercial software, as demonstrated in this study, simplifies the implementation of the test in clinical settings. Particularly for countries like Brazil, where the cost of CMA presents a substantial barrier to most of the population, LP-WGS emerges as a cost-effective alternative for investigating copy number changes in cytogenetics.

Models for predicting the risk of illness in leprosy contacts in Brazil: Leprosy prediction models in Brazilian contacts.

OBJECTIVE: This study aims to develop and validate predictive models that assess the risk of leprosy development among contacts, contributing to an enhanced understanding of disease occurrence in this population. METHODS: A cohort of 600 contacts of people with leprosy treated at the National Reference Center for Leprosy and Health Dermatology at the Federal University of Uberlândia (CREDESH/HC-UFU) was followed up between 2002 and 2022. The database was divided into two parts: two-third to construct the disease risk score and one-third to validate this score. Multivariate logistic regression models were used to construct the disease score. RESULTS: Of the four models constructed, model 3, which included the variables anti-phenolic glycolipid I immunoglobulin M positive, absence of Bacillus Calmette-Guérin vaccine scar and age ≥60 years, was considered the best for identifying a higher risk of illness, with a specificity of 89.2%, a positive predictive value of 60% and an accuracy of 78%. CONCLUSIONS: Risk prediction models can contribute to the management of leprosy contacts and the systematisation of contact surveillance protocols.

Effects of cancer-induced cachexia and administration of L-glutathione on the intestinal mucosa in rat.

Walker-256 tumor is an experimental model known to promote cachexia syndrome, oxidative stress, and systemic inflammation. This study evaluated the duodenal mucosa of rats with Walker-256 tumor administered with 1% L-glutathione, intending to evaluate the damage caused by cancer-associated cachexia in the gastrointestinal tract and the effects of antioxidant administration on mucosal protection. Twenty-four 55-day-old male Wistar rats were distributed into four groups: control (C); control administered with 1% L-glutathione (C-GSH); Walker-256 tumor (W) and Walker-256 tumor administered with 1% L-glutathione (W-GSH). After 14 days of treatment, the duodenum was harvested for morphometric analysis of the mucosa, proliferation, apoptosis, immunostaining of varicosities immunoreactive (IR) to vasoactive intestinal peptide (VIP) and 5-HT-IR cells, and quantification of mast cells and goblet cells. Walker-256 tumor-bearing rats showed cachexia syndrome, mucosal atrophy, reduced cell proliferation, reduced 5-HT-IR cells, and increased goblet cells and VIPergic varicosities, which were not reversed by L-glutathione. On the other hand, L-glutathione caused a reduction of cells in apoptosis and mast cell recruitment, demonstrating a partial recovery of the damage detected in the intestinal mucosa.

The possible impacts of nano and microplastics on human health: lessons from experimental models across multiple organs.

The widespread production and use of plastics have resulted in accumulation of plastic debris in the environment, gradually breaking down into smaller particles over time. Nano-plastics (NPs) and microplastics (MPs), defined as particles smaller than 100 nanometers and 5 millimeters, respectively, raise concerns due to their ability to enter the human body through various pathways including ingestion, inhalation, and skin contact. Various investigators demonstrated that these particles may produce physical and chemical damage to human cells, tissues, and organs, disrupting cellular processes, triggering inflammation and oxidative stress, and impacting hormone and neurotransmitter balance. In addition, micro- and nano-plastics (MNPLs) may carry toxic chemicals and pathogens, exacerbating adverse effects on human health. The magnitude and nature of these effects are not yet fully understood, requiring further research for a comprehensive risk assessment. Nevertheless, evidence available suggests that accumulation of these particles in the environment and potential human uptake are causes for concern. Urgent measures to reduce plastic pollution and limit human exposure to MNPLs are necessary to safeguard human health and the environment. In this review, current knowledge regarding the influence of MNPLs on human health is summarized, including toxicity mechanisms, exposure pathways, and health outcomes across multiple organs. The critical need for additional research is also emphasized to comprehensively assess potential risks posed by degradation of MNPLs on human health and inform strategies for addressing this emerging environmental health challenge. Finally, new research directions are proposed including evaluation of gene regulation associated with MNPLs exposure.

Autonomic modulation of heart rate during physical activity in pregnant women: A systematic review of literature.

BACKGROUND: There are important physiological changes in the heart rate autonomic modulation in pregnant women and these changes may affect the way their bodies respond to exercise stimulus. The objective of this review is to verify the physical exercise influence on autonomic modulation of heart rate in pregnant women. METHODS: This study is a Systematic Review. The electronic databases used to search for the studies were Cochrane Library, MEDLINE via PUBMED, Regional Health Portal and EMBASE. Experimental studies that evaluated heart-rate variability in pregnant women practicing physical exercises were included. And articles that addressed only fetal heart-rate variability, case reports, congress abstracts, clinical trial protocols without results, preprints, and gray literature were excluded. There were no language or publication year restrictions. The descriptors used in the Search were Cardiac Chronotropism, Sympathetic Nervous System, Pregnancy, and Physical Exercise. For statistical analysis, the fixed effect model was used. RESULTS: A total of 3106 articles were found, and 12 studies were included, which 5 were nonrandomized clinical trials, 4 were randomized clinical trials, and 3 were cross-sectional studies. Three hundred and four pregnant women were included in the studies. The application of physical exercise was varied, but in general they used aerobic exercises and with increased variability of the heart rate and reflex on the autonomic modulation of heart rate. CONCLUSION: Most studies demonstrate benefits heart rate in pregnant women, but limited research makes it hard to compare specific types of exercise and larger studies are needed to identify the best exercise.

Impacts of industrial actions, protests, strikes and lockouts by health and care workers during COVID-19 and other pandemic contexts: a systematic review.

BACKGROUND: Public health emergencies of international concern (PHEICs) as the COVID-19 pandemic and others that have occurred since the early 2000s put enormous pressure on health and care systems. This is being a context for protests by health and care workers (HCWs) because of additional workload, working conditions and effects on mental and physical health. In this paper, we intended to analyze the demands of HCWs associated with industrial actions, protests, strikes and lockouts (IAPSLs) which occurred during COVID-19 pandemic and other PHEICs; to identify the impact of these grievances; and describe the relevant interventions to address these IAPSLs. METHODS: We included studies published between January 2000 and March 2022 in PubMed, Embase, Scopus, BVS/LILACS, WHO's COVID-19 Research Database, ILO, OECD, HSRM, and Google Scholar for grey literature. Eligibility criteria were HCWs as participants, IAPSLs as phenomenon of interest occurring in the context of COVID-19 and other PHEICs. GRADE CERQual was used to assess risk of bias and confidence of evidence. RESULTS: 1656 records were retrieved, and 91 were selected for full-text screening. We included 18 publications. A system-wide approach, rather than a limited approach to institutions on strike, makes it possible to understand the full impact of the strike on health and care services. PHEICs tend to aggravate already adverse working conditions of HCWs, acting as drivers for HCWs strikes, leading to staff shortages, and financial issues, both in the North and in the Global South, particularly evident in Asia and Africa. In addition, issues related to deficiencies in leadership and governance in heath sector and lack of medical products and technologies (e.g., lack of personal protective equipment) were the main drivers of strikes, each contributing 25% of the total drivers identified. CONCLUSIONS: It is necessary to focus on the preparedness of health and care systems to respond adequately to PHEICs, and this includes being prepared for HCWs' IAPSLs, talked much in the context of COVID-19 pandemic. Evidence to assist policymakers in defining strategies to respond adequately to the health and care needs of the population during IAPSLs is crucial. The main impact of strikes is on the disruption of health care services' provision. Gender inequality being a major issue among HCWs, a proper understanding of the full impact of the strike on health and care services will only be possible if gender lens is combined with a systemic approach, rather than gender-undifferentiated approaches limited to the institutions on strike.

Impacts for health and care workers of Covid-19 and other public health emergencies of international concern: living systematic review, meta-analysis and policy recommendations.

BACKGROUND: Health and care workers (HCW) faced the double burden of the SARS-CoV-2 pandemic: as members of a society affected by a public health emergency and as HWC who experienced fear of becoming infected and of infecting others, stigma, violence, increased workloads, changes in scope of practice, among others. To understand the short and long-term impacts in terms of the COVID-19 pandemic and other public health emergencies of international concern (PHEICs) on HCW and relevant interventions to address them, we designed and conducted a living systematic review (LSR). METHODS: We reviewed literature retrieved from MEDLINE-PubMed, Embase, SCOPUS, LILACS, the World Health Organization COVID-19 database, the ClinicalTrials.org and the ILO database, published from January 2000 until December 2021. We included quantitative observational studies, experimental studies, quasi-experimental, mixed methods or qualitative studies; addressing mental, physical health and well-being and quality of life. The review targeted HCW; and interventions and exposures, implemented during the COVID-19 pandemic or other PHEICs. To assess the risk of bias of included studies, we used the Johanna Briggs Institute (JBI) Critical Appraisal Tools. Data were qualitatively synthetized using meta-aggregation and meta-analysis was performed to estimate pooled prevalence of some of the outcomes. RESULTS: The 1013 studies included in the review were mainly quantitative research, cross-sectional, with medium risk of bias/quality, addressing at least one of the following: mental health issue, violence, physical health and well-being, and quality of life. Additionally, interventions to address short- and long-term impact of PHEICs on HCW included in the review, although scarce, were mainly behavioral and individual oriented, aimed at improving mental health through the development of individual interventions. A lack of interventions addressing organizational or systemic bottlenecks was noted. DISCUSSION: PHEICs impacted the mental and physical health of HCW with the greatest toll on mental health. The impact PHEICs are intricate and complex. The review revealed the consequences for health and care service delivery, with increased unplanned absenteeism, service disruption and occupation turnover that subvert the capacity to answer to the PHEICs, specifically challenging the resilience of health systems.

Stress symptoms occur in patients undergoing chemotherapy treatment independently of the level of physical activity.

The cancer patient is undergoing a set of procedures that affect the physical and psychological balance, which can generate stressful situations in the organism. In turn, physical activity helps to treat stress, promoting well-being and reducing anxiety. Our study aimed to verify the influence of physical activity practice on stress symptoms in patients undergoing oncological chemotherapy treatment. For this, we used Lipp's Inventory of Stress Symptoms (ISSL) and the International Physical Activity Questionnaire (IPAQ) in 56 patients with cancer. Our data show that 45.4% of the participants exhibited stress scores, of which, 21.8% were at near to exhaustion, and 23.6% at exhaustion. We observed that 30% of them are considered sufficiently active, 25% insufficiently active, 45% sedentary. No association was observed between physical activity and stress. These findings indicate that stress symptoms occur in patients undergoing chemotherapy treatment regardless of the level of physical activity.

Prioritization criteria in policies and management of human resources for health: a proposal for a validated methodology.

Objective: To create and validate criteria for prioritizing problems related to policies and management of the health workforce. Methods: This methodological study was divided into three stages. First, the criteria were elaborated by means of a systematized literature review. Second, the criteria were evaluated online by a committee of judges comprised of eight specialists. In the third stage, an evaluation was carried out by the target audience in a hybrid workshop. The participants evaluated the material using the Suitability Assessment of Materials instrument, adapted for the research. Results: Three prioritization criteria (relevance, window of opportunity and acceptability) and a scoring scale were developed based on the literature review. In the evaluation by the committee of judges, the approval percentage of the criteria and prioritization method was 84%. Modifications were made based on suggestions in relation to the material presented to the specialists. In the pre-test stage, the approval percentage varied by item, with six of them reaching a maximum approval of 100% (corresponding to approximately 46% of the items), four reaching 92% and three achieving 83% each, indicating positive results. Conclusions: The developed criteria were considered valid for use in the context of policies and management in the area of human resources for health.

The metabolic interplay between dietary carbohydrate and exercise and its role in acute appetite regulation in males: a randomized controlled study.

An understanding of the metabolic determinants of postexercise appetite regulation would facilitate development of adjunctive therapeutics to suppress compensatory eating behaviours and improve the efficacy of exercise as a weight-loss treatment. Metabolic responses to acute exercise are, however, dependent on pre-exercise nutritional practices, including carbohydrate intake. We therefore aimed to determine the interactive effects of dietary carbohydrate and exercise on plasma hormonal and metabolite responses and explore mediators of exercise-induced changes in appetite regulation across nutritional states. In this randomized crossover study, participants completed four 120 min visits: (i) control (water) followed by rest; (ii) control followed by exercise (30 min at ∼75% of maximal oxygen uptake); (iii) carbohydrate (75 g maltodextrin) followed by rest; and (iv) carbohydrate followed by exercise. An ad libitum meal was provided at the end of each 120 min visit, with blood sample collection and appetite assessment performed at predefined intervals. We found that dietary carbohydrate and exercise exerted independent effects on the hormones glucagon-like peptide 1 (carbohydrate, 16.8 pmol/L; exercise, 7.4 pmol/L), ghrelin (carbohydrate, -48.8 pmol/L; exercise: -22.7 pmol/L) and glucagon (carbohydrate, 9.8 ng/L; exercise, 8.2 ng/L) that were linked to the generation of distinct plasma 1 H nuclear magnetic resonance metabolic phenotypes. These metabolic responses were associated with changes in appetite and energy intake, and plasma acetate and succinate were subsequently identified as potential novel mediators of exercise-induced appetite and energy intake responses. In summary, dietary carbohydrate and exercise independently influence gastrointestinal hormones associated with appetite regulation. Future work is warranted to probe the mechanistic importance of plasma acetate and succinate in postexercise appetite regulation. KEY POINTS: Carbohydrate and exercise independently influence key appetite-regulating hormones. Temporal changes in postexercise appetite are linked to acetate, lactate and peptide YY. Postexercise energy intake is associated with glucagon-like peptide 1 and succinate levels.

Encephalopathy Caused by Human Parvovirus B19 Genotype 1 Associated with Haemophilus influenzae Meningitis in a Newborn.

Parvovirus B19 infection is associated with a wide range of clinical manifestations, from asymptomatic to severe neurological disorders. Its major clinical symptoms, fever and rash, are common to multiple viruses, and laboratory tests to detect B19 are frequently not available. Thus, the impact of B19 on public health remains unclear. We report the case of a 38-day old girl admitted to São Paulo Clinical Hospital, Brazil, with an initial diagnosis of bacterial meningitis, seizures, and acute hydrocephalus. Antibiotic therapy was maintained for one week after admission and discontinued after negative laboratory results were obtained. Nine days after symptoms onset, a cerebral spinal fluid (CSF) sample revealed persistent pleocytosis. The complete B19 complete genome was subsequently identified in her CSF by a metagenomic next-generation sequencing approach. This report highlights the possible involvement of B19 in the occurrence of acute neurological manifestations and emphasizes that its possible involvement might be better revealed by the use of metagenomic technology to detect viral agents in clinical situations of unknown or uncertain etiology.

Understanding plant responses to saline waterlogging: insights from halophytes and implications for crop tolerance.

MAIN CONCLUSION: Saline and wet environments stress most plants, reducing growth and yield. Halophytes adapt with ion regulation, energy maintenance, and antioxidants. Understanding these mechanisms aids in breeding resilient crops for climate change. Waterlogging and salinity are two abiotic stresses that have a major negative impact on crop growth and yield. These conditions cause osmotic, ionic, and oxidative stress, as well as energy deprivation, thus impairing plant growth and development. Although few crop species can tolerate the combination of salinity and waterlogging, halophytes are plant species that exhibit high tolerance to these conditions due to their morphological, anatomical, and metabolic adaptations. In this review, we discuss the main mechanisms employed by plants exposed to saline waterlogging, intending to understand the mechanistic basis of their ion homeostasis. We summarize the knowledge of transporters and channels involved in ion accumulation and exclusion, and how they are modulated to prevent cytosolic toxicity. In addition, we discuss how reactive oxygen species production and cell signaling enhance ion transport and aerenchyma formation, and how plants exposed to saline waterlogging can control oxidative stress. We also address the morphological and anatomical modifications that plants undergo in response to combined stress, including aerenchyma formation, root porosity, and other traits that help to mitigate stress. Furthermore, we discuss the peculiarities of halophyte plants and their features that can be leveraged to improve crop yields in areas prone to saline waterlogging. This review provides valuable insights into the mechanisms of plant adaptation to saline waterlogging thus paving the path for future research on crop breeding and management strategies.

Extracellular vesicles in carcinoma microenvironment.

Cancer is a significant cause of death, precluding increasing life expectancy worldwide. That is a multifactorial disease initiated by intrinsic or extrinsic factors that induce cell differentiation into cancer cells. However, cancer development, progression, and metastasis are not controlled only by cancer cells. The entire environment around these cells, named tumor microenvironment (TME), influences tumor development and spread. The tumor microenvironment is formed by cancer cells and heterogenous nonmalignant cells integrated with a complex extracellular matrix. The main cellular components of the TME are cancer-associated fibroblasts (CAFs), T lymphocytes, B cells, tumor-associated macrophages (TAMs), dendritic cells (DC), natural killer (NK) cells, tumor-associated neutrophils (TANs), Stem Cells, Endothelial Cells and their soluble secreted extracellular vesicles (EVs) that modulate cancer cells to establish and disseminate. This review provides a recent insight into the role of EVs secreted from different populations of the TME associated with the initiation and progression of carcinoma.

A loss-of-function NCSTN mutation associated with familial Dowling Degos disease and hidradenitis suppurativa.

Dowling Degos disease (DDD) is a rare autosomal dominant genodermatosis characterized by acquired, slowly progressive reticulated pigmented lesions primarily involving flexural skin areas. Mutations in KRT5, POGLUT-1 and POFUT-1 genes have been associated with DDD, and loss-of-function mutations in PSENEN, a subunit of the gamma-secretase complex, were found in patients presenting with DDD or DDD comorbid with hidradenitis suppurativa (HS). A nonsense mutation in NCSTN, another subunit of the gamma-secretase, was already described in a patient suffering from HS and DDD but whether NCSTN could be considered a novel gene for DDD is still debated. Here, we enrolled a four-generation family with HS and DDD. Through Whole Exome Sequencing (WES) we identified a novel nonsense mutation in the NCSTN gene in all the affected family members. To study the impact of this variant, we isolated outer root sheath cells from patients' hair follicles. We showed that this variant leads to a premature stop codon, activates a nonsense-mediated mRNA decay, and causes NCSTN haploinsufficiency in affected individuals. In fact, cells treated with gentamicin, a readthrough agent, had the NCSTN levels corrected. Moreover, we observed that this haploinsufficiency also affects other subunits of the gamma-secretase complex, possibly causing DDD. Our findings clearly support NCSTN as a novel DDD gene and suggest carefully investigating this co-occurrence in HS patients carrying a mutation in the NCSTN gene.

Associations of the consumption of unprocessed red meat and processed meat with the incidence of cardiovascular disease and mortality, and the dose-response relationship: A systematic review and meta-analysis of cohort studies.

OBJECTIVES: The aim of this study was to examine the associations of unprocessed red meat and processed meat consumption with cardiovascular disease (CVD) incidence and mortality, and the dose-response relationship. METHODS: Published literature was retrieved through a structured search of 10 electronic databases: MEDLINE/PubMed, Scopus, SciELO, LILACS, ScienceDirect, Web of Science, Cochrane (CENTRAL), WHOLIS, PAHO and Embase, without language or year of publication restrictions. In addition, we searched the references of published studies. This systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes: The PRISMA Statement. RESULTS: Twenty-one prospective cohort studies were included in the systematic review. The CVDs evaluated in the inserted studies were stroke, heart failure (HF) and coronary heart disease (CHD). Considering the heterogeneity found in the studies, for the meta-analysis, 9 articles were included. The results presented in the meta-analysis of the association of consumption of unprocessed red meat and CVD indicated that there was a significant association with total stroke incidence (RR 1.10; 95%; CI 1.01 to 1.19; p = 0.02). There was no association with Ischemic stroke incidence, nor CHD Mortality with consumption of unprocessed red meat. However, for Hemorrhagic Stroke Mortality the assessment in the consumption of unprocessed red meat showed an association of protection for women (RR 0.64; 95%; CI 0.45 to 0.91; p = 0.01). As for the results of the meta-analysis of the association between consumption of processed meat and CVD, they indicated that there was a significant association with total stroke incidence (RR 1.17; 95%; CI 1.08 to 1.26; p < 0.0001). There was no association with Ischemic stroke, nor with CHD Mortality with consumption of processed meat. Some studies that showed no association of risk, presented a significant linear trend dose response for the association of the consumption of unprocessed red meat (Bernstein et al. 2010; Nagao et al. 2012) or processed meat (Bernstein et al. 2012) and CVD. CONCLUSION: According to the results found in the meta-analysis, the consumption of unprocessed red meat and processed meat are associated with the incidence of stroke, however, no positive association was observed in relation to mortality from CVD. This systematic review and meta-analysis protocol was registered on the PROSPERO (number: CRD42019100914).

Trends and challenges in analytical chemistry for multi-analysis of illicit drugs employing wastewater-based epidemiology.

Wastewater-based epidemiology (WBE) for quantification of illicit drug biomarkers (IDBs) in wastewater samples is an effective tool that can provide information about drug consumption. The most commonly quantified IDBs belong to different chemical classes, including cocaine, amphetamine-type stimulants, opioids, and cannabinoids, so the different chemical properties of these molecules pose a challenge in the development of analytical methods for multi-analyte analysis. Recent workflows include the steps of sampling and storage, sample preparation using solid-phase extraction (SPE) or without extraction, and quantification of analytes employing gas or liquid chromatography coupled with mass spectrometry. The greatest difficulty is due to the fact that wastewater samples are complex chemical mixtures containing analytes with different chemical properties, often present at low concentrations. Therefore, in the development of analytical methods, there is the need to simplify and optimize the analytical workflows, reducing associated uncertainties, analysis times, and costs. The present work provides a critical bibliographic survey of studies published from the year 2020 until now, highlighting the challenges and trends of published analytical workflows for the multi-analysis of IDBs in wastewater samples, considering sampling and sample preparation, method validation, and analytical techniques.

Delayed recovery from ataxic dementia following liposuction.

A 19-year-old student developed hypoventilation and cyanosis at the end of a cosmetic liposuction procedure. She was awake, but severely abulic, disoriented, and unable to stand and walk due to severe locomotor ataxia. Neuropsychological evaluation showed psychomotor slowness, and deficits in memory encoding and retrieval, and on executive, and visuospatial and visuoperceptual tests; oral comprehension and constructional praxis were spared. ¹H-MRS showed a reduction of NAA. A year later, her cognitive and neurological exam, and NAA returned to normal, and she resumed her normal life. The severity of the acute manifestations of hypoxic encephalopathy not always entail a poor prognosis.

Influence of conditioned medium from squamous cell carcinoma of the tongue on lymphoblasts and peripheral blood mononuclear cells.

BACKGROUND: Squamous cell carcinoma (SCC) is the most common malignant neoplasm of the oral cavity and is associated with high morbidity and mortality. Attention has been given to the role of inflammatory cells in carcinogenesis because of the ability of cancer cells to subvert the immune response. However, little is known about how molecules from neoplastic cells interact with lymphoblasts and circulating immune cells. This study aimed to understand the mechanisms by which SCC cells modulate the immune response by analyzing the influence of conditioned medium derived from SCC cell lines on immune cells. METHODS: Lymphoblastic cells (CEM) and peripheral blood mononuclear cells (PBMC) were cultured in a conditioned medium derived from squamous cell carcinoma cells (SCC9 or SCC4) and analyzed for cell viability, CD4/CD8/FOXP3 profile by flow cytometry, and chemokine levels. RESULTS: Conditioned medium derived from SCC4 and SCC9 presented higher concentrations of IL-6 and IL-8 than IL-1ß, IL-10, and IFN-γ. CEM and PBMCs when cultured with conditioned medium derived from SCC4 and SCC9 reduced IL-1ß, IL-8, and IFN-γ concentrations. Conditioned medium from SCC4 increased CD4+ population in both CEM and PBMCs, while in conditioned medium from SCC9 it occurred only in PBMCs. PBMCs when cultured with both conditioned mediums increased CD8+ /FOXP3+ cells. CEM cells when cultured with conditioned medium derived from SCC4 and SCC9 reduced. CONCLUSION: Collectively, our results suggest that the products derived from squamous cell carcinoma on inflammatory cells can promote an immunosuppressed environment by reducing cell viability, changing cytokine expression, and altering the cell immunoprofile.

Implementation of policy and management interventions to improve health and care workforce capacity to address the COVID-19 pandemic response: a systematic review.

BACKGROUND: The COVID-19 pandemic highlighted pre-existing weaknesses in health and care systems and services and shortages of health and care workers (HCWs). As a result, policymakers needed to adopt measures to improve the health and care workforce (HCWF) capacity. This review aims to identify countries' range of policies and management interventions implemented to improve HCWs' capacity to address the COVID-19 pandemic response, synthesize their evidence on effectiveness, and identify gaps in the evidence. METHODS: The literature was searched in PubMed, Embase, Scopus, LILACS-BVS, WHO's COVID-19 Research Database and the ILO, OECD and HSRM websites for literature and documents published between January 2020 and March 2022. Eligibility criteria were HCWs as participants and policy and management interventions aiming to improve HCWF capacity to address the COVID-19 pandemic response. Risk of bias was assessed with Joanna Briggs Institute (JBI) Critical Appraisal Tools (CAT) and certainty of the evidence in presented outcomes with GRADE. RESULTS: The searches retrieved 3378 documents. A total of 69 were included, but only 8 presented outcomes of interventions implemented. Most of the selected documents described at least one intervention implemented by countries at the organizational environment level to increase the flexibility and capacity of the HCWF to respond to the pandemic, followed by interventions to attract and retain HCWs in safe and decent working environments. There was a lack of studies addressing social protection, human resources for health information systems, and regarding the role of community health workers and other community-based providers. Regarding the risk of bias, most of documents were rated as medium or high quality (JBI's CAT), while the evidence presented for the outcomes of interventions was classified as mostly low-certainty evidence (GRADE). CONCLUSIONS: Countries have implemented various interventions, some innovative, in response to the pandemic, and others had their processes started earlier and accelerated by the pandemic. The evidence regarding the impact and efficacy of the strategies used by countries during the pandemic still requires further research.

Protective effects of a chemically characterized extract from solanum torvum leaves on acetaminophen-induced liver injury.

Distinct parts of Solanum torvum Swartz. (Solanaceae) are popularly used for a variety of therapeutic purposes. This study determined the phytochemical composition of a phenolic fraction of S. torvum leaf aqueous extract and investigated its antioxidant and liver-protective properties. A phenolic compound-enriched fraction, or phenolic fraction (STLAE-PF) of an infusion (STLAE) of S. torvum leaves, was tested in vitro (antagonism of H2O2 in cytotoxicity and DCF assays with HepG2/C3A cells), and in vivo for antioxidant activity and protective effects against acetaminophen (APAP)-induced liver injury in mice. Thirty-eight compounds (flavonoids, esters of hydroxycinnamic acid, and chlorogenic acid isomers) were tentatively identified (high-performance liquid chromatography coupled to high-resolution electrospray mass spectrometry) in the STLAE-PF fraction. In vitro assays in HepG2/C3A cells showed that STLAE-PF and some flavonoids contained in this phenolic fraction, at noncytotoxic levels, antagonized in a concentration-dependent manner the effects of a powerful oxidant agent (H2O2). In C57BL/6 mice, oral administration of STLAE (600 and 1,200 mg/kg bw) or STLAE-PF (300 mg/kg bw) prevented the rise in serum transaminases (ALT and AST), depletion of reduced glutathione (GSH) and elevation of thiobarbituric acid reactive species (TBARs) levels in the liver caused by APAP (600 mg/kg bw, i.p.). The hepatoprotective effects of STLAE-PF (300 mg/kg bw) against APAP-caused liver injury were comparable to those of N-acetyl-cysteine (NAC 300 or 600 mg/kg bw i.p.). These findings indicate that a phenolic fraction of S. torvum leaf extract (STLAE-PF) is a new phytotherapeutic agent potentially useful for preventing/treating liver injury caused by APAP overdosing.