The latency to awake from induced-obstructive sleep apnea is reduced in rats with chronic epilepsy.

OSA is known to increase the risk for SUDEP in persons with epilepsy, but the relationship between these two factors is not clear. Also, there is no study showing the acute responses to obstructive apnea in a chronic epilepsy model. Therefore, this study aimed to characterize cardiorespiratory responses to obstructive apnea and chemoreceptor stimulation in rats. In addition, we analyzed respiratory centers in the brain stem by immunohistochemistry. Epilepsy was induced with pilocarpine. About 30-60 days after the first spontaneous seizure, tracheal and thoracic balloons, and electrodes for recording the electroencephalogram, electromyogram, and electrocardiogram were implanted. Intermittent apneas were made by inflation of the tracheal balloon during wakefulness, NREM sleep, and REM sleep. During apnea, respiratory effort increased, and heart rate fell, especially with apneas made during wakefulness, both in control rats and rats with epilepsy. Latency to awake from apnea was longer with apneas made during REM than NREM, but rats with epilepsy awoke more rapidly than controls with apneas made during REM sleep. Rats with epilepsy also had less REM sleep. Cardiorespiratory responses to stimulation of carotid chemoreceptors with cyanide were similar in rats with epilepsy and controls. Immunohistochemical analysis of Phox2b, tryptophan hydroxylase, and NK1 in brain stem nuclei involved in breathing and sleep (retrotrapezoid nucleus, pre-Bötzinger complex, Bötzinger complex, and caudal raphe nuclei) revealed no differences between control rats and rats with epilepsy. In conclusion, our study showed that rats with epilepsy had a decrease in the latency to awaken from apneas during REM sleep, which may be related to neuroplasticity in some other brain regions related to respiratory control, awakening mechanisms, and autonomic modulation.

Fusarium keratitis in a Brazilian tropical semi-arid area: Clinical-epidemiological features, molecular identification and antifungal susceptibility.

BACKGROUND: Fungal keratitis is a severe eye infection that can result in blindness and visual impairment, particularly in developing countries. Fusarium spp. are the primary causative agents of this condition. Diagnosis of Fusarium keratitis (FK) is challenging, and delayed treatment can lead to serious complications. However, there is limited epidemiological data on FK, especially in tropical areas. OBJECTIVES: This study aimed to describe the clinical, laboratorial and epidemiological characteristics of FK in a tropical semi-arid region of Brazil. PATIENTS/METHODS: Adult patients with laboratory-confirmed FK diagnosed between October 2019 and March 2022 were evaluated. Fusarium isolates were characterized at molecular level and evaluated regarding antifungal susceptibility. RESULTS: A total of 226 clinical samples from patients suspected of keratitis were evaluated; fungal growth was detected in 50 samples (22.12%); out of which 42 were suggestive of Fusarium spp. (84%). Molecular analysis of a randomly selected set of 27 isolates identified F. solani species complex (n = 14); F. fujikuroi sensu lato (n = 6) and F. dimerum sensu lato (n = 7); a total of 10 haplotypes were identified among the strains. All but one Fusarium strains were inhibited by amphotericin B, natamycin and fluconazole. Most patients were male (71.42%; 30 out of 42), aged from 27 to 73 years old. Trauma was the most important risk factor for FK (40.47%; 17 out of 42). Patients were treated with antifungals, corticoids and antibiotics; keratoplasty and eye enucleation were also performed. CONCLUSIONS: The study provided insights into the characteristics of FK in tropical regions and emphasized the importance of enhanced surveillance and management strategies.

Heated environment increases blood pressure drop and postural sway during initial orthostasis in healthy subjects.

PURPOSE: We tested the hypothesis that heat stress influences the closed-loop cardio-postural control by an increased blood pressure (BP) drop and postural sway. METHODS: Fourteen healthy individuals (eight women) performed two orthostatic tests under thermal reference (TC; ~ 24 ºC) and HOT (~ 38 ºC) conditions. The center-of-pressure (COP) displacements and the electromyography (EMG) activity of the calf muscles (medial gastrocnemius and tibialis anterior) were recorded during the initial orthostasis (ORT onset) after the supine-to-stand challenge. At the same period, BP (beat-to-beat) was continuously monitored, and supine-to-stand variations (∆%) were calculated. Sublingual temperature (Tsl) was measured as a surrogate of internal temperature. RESULTS: Tsl increased in HOT compared to TC (TC 36.5 ± 0.3 vs. HOT 36.7 ± 0.3 ºC; p < 0.01). COP distance was greater in HOT compared to TC condition (TC 596.6 ± 242.4 vs. HOT 680.2 ± 249.1 mm; p < 0.01). EMG activity of the gastrocnemius decreased in HOT compared to TC condition (TC 95.5 ± 19.8 vs. HOT 78.4 ± 22.8%mV; p = 0.02). EMG of tibialis did not change between TC and HOT (TC 83.5 ± 42.9 vs. HOT 66.1 ± 31.9% mV; p = 0.29). BP showed a greater fall in HOT compared to TC condition (∆%TC - 24.5 ± 13.2 vs. ∆%HOT - 33.2 ± 20.2%; p = 0.01). CONCLUSION: Heat stress causes a greater fall in blood pressure and a reduction in musculoskeletal pump activity during orthostatic onset. These effects could be potential mechanisms that underlie augmented postural instability under a heated environment.

Artisanal mining of monazite and cassiterite in the Amazon: Potential risks of rare earth elements for the environment and human health.

Artisanal mining is intensely carried out in developing countries, including Brazil and especially in the Amazon. This method of mineral exploration generally does not employ mitigation techniques for potential damages and can lead to various environmental problems and risks to human health. The objectives of this study were to quantify the concentrations of rare earth elements (REEs) and estimate the environmental and human health risks in cassiterite and monazite artisanal mining areas in the southeastern Amazon, as well as to understand the dynamics of this risk over time after exploitation. A total of 35 samples of wastes classified as overburden and tailings in active areas, as well as in areas deactivated for one and ten years were collected. Samples were also collected in a forest area considered as a reference site. The concentrations of REEs were quantified using alkaline fusion and ICP-MS. The results were used to calculate pollution indices and environmental and human health risks. REEs showed higher concentrations in anthropized areas. Pollution and environmental risk levels were higher in areas deactivated for one year, with considerable contamination factors for Gd and Sm and significant to extreme enrichment factors for Sc. Human health risks were low (< 1) in all studied areas. The results indicate that artisanal mining of cassiterite and monazite has the potential to promote contamination and enrichment by REEs.

Energy metabolism and respirometry of lambs fed sun or shade dried hays of banana crop residues.

We aimed to evaluate the effects of different drying methods for banana residues on the energy metabolism and respirometry of growing lambs. Twenty Santa Inês x Dorper lambs were fed five experimental diets: Tifton 85 grass hay (Control), shade-dried banana leaf hay (LH Shade), shade-dried pseudostem banana hay (PH Shade), sun-dried banana leaf hay (LH Sun), and sun-dried banana pseudostem hay (PH Sun). Nutrient intake and digestibility were assessed in metabolic cages, whereas O2 consumption and CO2, methane, and heat production were measured in a respirometry chamber with animals fed at maintenance and ad libitum levels. Nutrient and energy intake was not influenced by diet. Pseudostem hay had higher apparent digestibility of dry matter (71.5%), organic matter (72.4%), and neutral detergent fiber (58.0%). However, this led to greater energy loss in the form of methane (12.1%). The banana residue hays and drying methods did not alter oxygen consumption, CO2 production, or heat production of animals fed ad libitum or during maintenance. On the other hand, the use of leaf hay resulted in a reduction of 24.7% in enteric methane production of animals fed ad libitum. The inclusion of pseudostem hay is recommended in sheep feedlot diet. This residue provided greater use of DM, however promoted a greater loss of energy in the form of methane, resulting in similar energy consumption. The drying methods did not reduce the availability of nutrients and the sun drying method is recommended, since it is a faster drying method.

Self-mutilation: a systematic review.

Self-mutilation lesions can represent a clinical diagnosis challenge for healthcare professionals, as patients do not admit to self-mutilation. This leads to failed diagnoses due to the similarity of this condition to other diseases. Searches on the subject were carried out at the PubMed, Periódicos Capes, Scopus, Science Direct and WoS databases, according to the following inclusion criteria: articles in English, Portuguese or Spanish, published from 2018 to June 2023, encompassing case reports, case series and literature reviews. Men are slight more affected by self-mutilation injuries, also presenting the most serious lesions. Self-mutilation injuries are reported globally, mostly in the Asian and American continents. Clinical presentations are varied, but morphology is, in most cases, associated to the form/instrument used for self-mutilation. Greater evidence of diagnosed mental disorders in women and underreporting of these cases in men due to low demands for specialized treatment are noted. A higher prevalence of self-mutilation lesions was verified for men, affecting a wide age range, with the highest number of cases in the USA. The most affected body areas are arms and external genitalia, mostly due to knife use. An association between self-mutilation injuries and mental disorders is clear, with most cases being previously undiagnosed.

Blocking activation of CD4-CD8- T cells modulates their cytotoxic potential and decreases the expression of inflammatory and chemotactic receptors.

CD4-CD8- (double negative - DN) T cells represent a small fraction of circulating T lymphocytes but are a major source of pro-inflammatory cytokines in patients with infectious diseases, including chronic Chagas cardiomyopathy (CCC), one of the deadliest cardiopathies known. Chagas disease is caused by an infection with the protozoan parasite Trypanosoma cruzi and can lead to either an asymptomatic form or a high-mortality cardiac disease. While circulating DN T cells represent a major inflammatory cytokine-expressing cell population in Chagas disease, their potential to be recruited to the heart and to perform cytotoxicity has not been determined. Our previous studies showed that blocking DN T cell activation decreases the expression of IFN-gamma, a cytokine involved in the severity of CCC. Here, studying a well-characterized cohort of Chagas patients with CCC or the asymptomatic form of Chagas disease (indeterminate form, IND), we evaluated the expression of cytotoxic molecules, cytokine and chemokine receptors in γδ+ and αß+ DN T cells by multiparameter flow cytometry, and investigated whether blocking the activation of DN T cells influences the expression of these molecules. We observed that DN T cells from CCC display a higher expression of granzyme A, perforin, inflammatory molecules, and inflammatory chemokine receptors than cells from IND. Messenger RNA coding for these molecules is also upregulated in the heart of CCC patients. Importantly, blocking the activation of DN T cells from CCC modulates their cytotoxic potential and the expression of inflammatory and of chemokine receptors, suggesting that targeting DN T cell activation may be a valid strategy to reduce recruitment to the heart, inflammation, cytotoxicity and, thereby diminish CCC progression and severity.

Osteoprotective effect by interleukin-4 (IL-4) on lipoprotein-induced periodontitis.

Lipoproteins are immunostimulatory bacterial components suggested to participate in inflammation-induced bone loss in periodontal disease through stimulation of osteoclast differentiation. Toll-like receptor 2 activation by Pam2CSK4 (PAM2), known to mimic bacterial lipoproteins, was previously shown to enhance periodontal bone resorption in mice. The anti-inflammatory cytokine interleukin-4 (IL-4) is a known inhibitor of RANKL-induced bone resorption in vitro. Here, we have investigated whether IL-4 could decrease PAM2-induced periodontal bone loss and osteoclastogenesis in vivo. In a model of periodontitis induced by gingival injections of PAM2 in mice, concomitant injections of IL-4 reduced bone loss. Histologically, IL-4 reduced the recruitment of inflammatory cells and the formation of TRAP+ osteoclasts stimulated by PAM2. Mouse bone marrow macrophages (BMMs) and neonatal calvarial osteoblasts were used to assess the effect of IL-4 on PAM2-induced osteoclastogenesis in vitro. In RANKL-primed BMMs stimulated by PAM2 Nfatc1, Ctsk, and Acp5 gene expression was up-regulated and resulted in robust formation of TRAP+ multinucleated osteoclasts, effects which were impaired by IL-4. These effects were mediated by impairment in PAM2-induced c-fos expression. In primary calvarial osteoblast cultures, IL-4 decreased PAM2-induced Tnfsf11 (encoding RANKL) mRNA and enhanced Tnfrsf11b (encoding OPG) expression. Our data demonstrate that the osteoprotective effect by IL-4 on lipoprotein-induced periodontal disease occurs through the inhibition of osteoclastogenesis by three mechanisms, one by acting directly on osteoclast progenitors, another by acting indirectly through decreasing the expression of osteoclast-regulating cytokines in osteoblasts and a third by decreasing inflammation.

Ascending renal infection following experimental candiduria by Candida tropicalis in immunocompromised mice.

The present study evaluated renal infection resulting from the implantation of C. tropicalis in the bladder of immunosuppressed mice. Yeasts were implanted in two manners: planktonic and via preformed biofilm on a small catheter fragment (SCF). Renal histopathology and cultures was performed 72 and 144 h after cystotomy was carried out in mice from three groups: group I contained non-contaminated mice implanted with a sterile SCF; group II mice received a sterile SCF plus a yeast suspension containing 1 × 107 yeasts/mL in a planktonic form; group III mice were implanted with a SCF containing preformed C. tropicalis biofilm. Viable yeasts were found in the kidneys of mice from both groups II and III. However, after 72 h the planktonic cells (group II) invaded more quickly than the sessile cells (group III). Over a longer period (144 h), group III exhibited a more invasive infection (50% of the animals presented renal infection and the renal fungal load was 3.2 log10 CFU/g tissue) than in group II, where yeasts were not found. C. tropicalis introduced into the bladder in two ways (in planktonic or biofilm form) were able to reach the kidney and establish a renal fungal infection, causing interstitial disorders. The data of the present study therefore support the hypothesis of an ascending pathway for renal infections by C. tropicalis. Furthermore, the biofilm resulted in a greater and progressive risk of renal infection, attributed to the slow detachment of the yeasts.

Strongyloides infection screening in transplant candidates: What is the best strategy?

BACKGROUND: The potential that Strongyloides stercoralis infection has to cause major morbidity and high mortality when the disseminated form occurs in transplant patients is of particular concern. METHODS: In this study, the objective was to observe S. stercoralis infection in patients who are candidates for transplantation by using parasitological, serological, and molecular techniques and to propose an algorithm for the detection of that infection in transplant candidates. RESULTS: By parasitological techniques, 10% of fecal samples were positive. Anti-Strongyloides antibodies immunoglobulin G were detected in 19.3% and 20.7% of patients by immunofluorescence assay and enzyme-linked immunosorbent assay, respectively. S. stercoralis DNA was observed in 17.3% of samples by conventional polymerase chain reaction and 32.7% of samples by quantitative polymerase chain reaction (qPCR). CONCLUSION: The set of results allows us to reinforce that a positive result by parasitological techniques and/or qPCR indicates that the specific treatment should be applied. However, the improvement of diagnostic techniques may suggest changes in the screening for strongyloidiasis in these patients.

[Evidence of effectiveness of hospital transition care in the elderly: rapid systematic reviewEvidencia de la eficacia de la atención transitoria prestada a las personas mayores después de la hospitalización: revisión sistemática rápida]. / Evidências de efetividade dos cuidados de transição em idosos após internação hospitalar: uma revisão sistemática rápida.

Objective: To synthesize the evidence on the effectiveness of hospital transition care in the elderly to support decision-making. Method: This rapid systematic review followed the recommendations of the Cochrane Rapid Reviews Methods Group. Studies were selected from the PubMed, EMBASE, Cochrane Library, and Virtual Health Library (BVS) databases using the following criteria: focus on the elderly as population; provision of hospital transition care as intervention; care as usual (non-transition care) as comparator; and effectiveness of the presence vs. absence of transition care as the outcome, with effectiveness defined as improvement in any evaluated parameter. Systematic reviews published in Portuguese, English, or Spanish, with or without meta-analysis, that assessed hospital transition care in elderly individuals were included. Studies lacking a description of the intervention and target population were excluded. Results: Of the 207 identified reviews, 18 were included. The studies were conducted in 21 countries, with 10 studies conducted in Europe and one in Brazil. The effectiveness of care for the elderly was demonstrated through increased adherence to medication regimens, reduced adverse events and medication-related errors, improved functional status, reduced falls, and reduced healthcare costs. Conclusions: Despite the evidence indicating the effectiveness of hospital transition care, further research is needed to develop more robust indicators of clinical improvement and integration into healthcare systems.

Objetivo: Sintetizar la evidencia sobre la eficacia de la atención transitoria prestada a las personas mayores después del alta hospitalaria con el fin de ayudar a los gerentes en la toma de decisiones. Métodos: En esta revisión sistemática rápida se siguieron las recomendaciones del Grupo Cochrane de Métodos de Revisiones Rápidas y se seleccionaron estudios en las bases de datos PubMed, EMBASE, Biblioteca Cochrane y Biblioteca Virtual de Salud. Para la selección de los estudios se consideraron los siguientes criterios: como población, personas mayores; como intervención, la prestación de atención transitoria después del alta hospitalaria; como comparador, la ausencia de atención transitoria después del alta hospitalaria; y como resultado, la eficacia del uso frente a la falta de uso de la atención transitoria, tomando como definición de eficacia la mejora de cualquier parámetro evaluado. Se incluyeron revisiones sistemáticas publicadas en español, inglés o portugués, con o sin metanálisis, en las cuales se evaluara la atención transitoria prestada a personas mayores después del alta hospitalaria y se excluyeron los estudios sin descripción de la intervención o del público destinatario correspondientes. Resultados: Se incluyeron 18 de las 207 revisiones halladas. Los estudios se habían realizado en 21 países (10 estudios en Europa y uno en Brasil). Se demostró la eficacia de la atención prestada a las personas mayores en cuanto a una mayor observancia de los tratamientos farmacológicos, una reducción del número de eventos adversos y errores en el uso de los medicamentos, una mejora del estado funcional de las personas mayores, una disminución de las caídas y un menor costo de la atención. Conclusiones: A pesar de haberse comprobado la eficacia de la atención transitoria, se necesitan nuevas investigaciones para elaborar indicadores más sólidos de la mejora clínica y de la integración en los sistemas de salud.

Heated environment offsets the cardiovascular responses to prolonged rowing exercise in competitive athletes.

Prolonged rowing exercise sessions are often prescribed considering competitive training schedules, and under hostile environments (e.g., heated ambient). The study aimed to investigate the effect of heat stress (HS) on physical performance, Lactate concentration ([Lac]), and cardiorespiratory responses during prolonged exercise sessions in competitive rowers. Twelve rowers performed preliminary exercise tests (2-km test and five-step incremental lactate test) to assess the target workload intensity corresponding to a 2.5 mmol.L-1 of [Lac]. On two separate days, participants were enrolled in two exercise sessions of 12 km in a rowing machine under HS (∼30 °C) and thermal comfort (TC 22 °C) conditions. Heart rate (HR), stroke volume (SV), cardiac output (CO), oxygen uptake (VO2), [Lac], and the rating of perceptual exertion (RPE) were obtained. From baseline, HS increased the maximum temperature of the face compared to TC. Workload and VO2 reduced while RPE increased at 9- and 12-km of rowing exercise under HS compared to TC. From baseline to the last stage of exercise, HS shifted SV downwards and HR upwards compared to TC. Consequently, CO did not change between thermal conditions (TC vs. HS). Therefore, HS provokes a cardiovascular drift during prolonged rowing in comparison to TC. The last stages of prolonged rowing sessions under HS seem to be critical to physical performance and relative perceptual of effort in rowers.

Efficacy of Carotenoid-Loaded Gelatin Nanoparticles in Reducing Plasma Cytokines and Adipocyte Hypertrophy in Wistar Rats.

The present study investigated the effect of gelatin-based nanoparticles (EPG) loaded with a carotenoid-rich crude extract (CE) on systemic and adipose tissue inflammatory response in a model with inflammation induced by a high glycemic index and high glycemic load diet (HGLI). Nanoparticles synthesized were characterized by different physical and chemical methods. The in vivo investigation evaluated Wistar rats (n = 20, 11 days, adult male with 21 weeks) subdivided into untreated (HGLI diet), conventional treatment (nutritionally adequate diet), treatment 1 (HGLI + crude extract (12.5 mg/kg)), and treatment 2 (HGLI + EPG (50 mg/kg)) groups. Dietary intake, caloric intake and efficiency, weight, inflammatory cytokines tissue concentration, visceral adipose tissue (VAT) weight, histopathological analysis, and antioxidant activity in plasma and VAT were investigated. EPG showed the same physical and chemical characteristics as previous batches (95.2 nm, smooth surface, and chemical interactions between materials). The EPG-treated group was the only group promoting negative ∆dietary intake, ∆caloric efficiency, and ∆weight. In addition, it presented a significant reduction (p < 0.05) in IL-6 and leptin levels and a greater presence of multilocular adipocytes. The results suggest that EPG can act as a nutraceutical in adjuvant therapy for treating inflammatory diseases associated with adipose tissue accumulation.

New Palladium(II) Complexes Containing Methyl Gallate and Octyl Gallate: Effect against Mycobacterium tuberculosis and Campylobacter jejuni.

This work describes the preparation, characterization and antimicrobial activity of four palladium(II) complexes, namely, [Pd(meg)(1,10-phen)] 1, [Pd(meg)(PPh3)2] 2, [Pd(og)(1,10-phen)] 3 and [Pd(og)(PPh3)2] 4, where meg = methyl gallate, og = octyl gallate, 1,10-phen = 1,10-phenanthroline and PPh3 = triphenylphosphine. As to the chemical structures, spectral and physicochemical studies of 1-4 indicated that methyl or octyl gallate coordinates a palladium(II) ion through two oxygen atoms upon deprotonation. A chelating bidentate phenanthroline or two triphenylphosphine molecules complete the coordination sphere of palladium(II) ion, depending on the complex. The metal complexes were tested against the Mycobacterium tuberculosis H37Rv strain and 2 exhibited high activity (MIC = 3.28 µg/mL). As to the tests with Campylobacter jejuni, complex 1 showed a significant effect in reducing bacterial population (greater than 7 log CFU) in planktonic forms, as well as in the biomass intensity (IBF: 0.87) when compared to peracetic acid (IBF: 1.11) at a concentration of 400 µg/mL. The effect provided by these complexes has specificity according to the target microorganism and represent a promising alternative for the control of microorganisms of public health importance.

Concentrations of iron and chromium in free-ranging common marmosets (Callithrix jacchus) from Pernambuco, Brazil.

Common marmosets (Callithrix jacchus) are widely distributed in Northeast Brazil and often inhabit urban and peri-urban forest areas close to human settlements. Given its wide territorial distribution, its proximity to human populations, and its exposure to environmental degradations originating from urbanization, common marmosets have a high potential for environmental biomonitoring. The concentrations of iron (Fe) and chromium (Cr) were quantified in the liver, hair, and bone of 22 free-ranging common marmosets' bodies from nine cities from Pernambuco State, Brazil, using inductively coupled plasma optical emission spectrometry (ICP OES). The liver showed the highest concentrations of Fe and Cr (3773.2 ± 3715.8 mg/kg and 19.4 ± 41.6 mg/kg, respectively); the lowest concentration of Fe was detected in the bone (111.6 ± 97.6 mg/kg) and of Cr in the hair (3.3 ± 1.5 mg/kg). There was a moderate positive correlation between Fe and Cr in the liver (r = 0.64) and a high negative correlation for Cr between bone and hair (r = -0.65). This study demonstrated the bioaccumulation of Fe and Cr in hair, liver, and bone in common marmosets. The highest average concentration of Fe and Cr occurred in animals from Recife, Jaboatão dos Guararapes, and Paulista, respectively, the 1st, the 2nd, and the 5th most populated cities in the state of Pernambuco. The presence of high concentrations of metals in animals from Recife and nearby cities can indicate alarming levels of environmental pollution in these locations.

Municipal solid waste management with recyclable potential in developing countries: Current scenario and future perspectives.

Municipal solid waste (MSW) is a complex challenge to be solved worldwide, intensified in developing countries since in addition to economic and environmental aspects there is also the social aspect represented by the collector individual. From an integrative bibliographic review this study longitudinally analyses the socio-productive inclusion of collectors in the municipal solid waste management (MSWM) at an international level. Aiming: (a) to identify relevant articles describing/studies on MSWM with social inclusion of scavengers around the world; (b) to analyse these articles in order to present its main characteristics; (c) to describe municipal solid waste management with recyclable potential (MSWRP) with socio-productive inclusion of collectors; (d) the study provides a more detailed summary of MSWRP management in some developing countries: Brazil, China, India, Indonesia, Mexico, Nigeria and Pakistan; and (e) to provide a framework indicating the future practices and perspectives of MSWRP. As result, this study presents the paradigms and future questions for an effective improvement of WSWM, such as: Professional Training of Scavengers, Cultural Issues, Empowerment of Scavenger, Recycling Cooperatives and Cooperativism, Policy Issues and Recycling Chain, Management Systems and Process Improvement, Quality of Services Provided, Circular Economy and Informal Sector, Health Quality and Safety at Work, Barriers and Solutions for the Inclusion of the Informal Sector, Environmental, Economic and Social Benefits.

Lipid droplets fuel SARS-CoV-2 replication and production of inflammatory mediators.

Viruses are obligate intracellular parasites that make use of the host metabolic machineries to meet their biosynthetic needs. Thus, identifying the host pathways essential for the virus replication may lead to potential targets for therapeutic intervention. The mechanisms and pathways explored by SARS-CoV-2 to support its replication within host cells are not fully known. Lipid droplets (LD) are organelles with major functions in lipid metabolism, energy homeostasis and intracellular transport, and have multiple roles in infections and inflammation. Here we described that monocytes from COVID-19 patients have an increased LD accumulation compared to SARS-CoV-2 negative donors. In vitro, SARS-CoV-2 infection were seen to modulate pathways of lipid synthesis and uptake as monitored by testing for CD36, SREBP-1, PPARγ, and DGAT-1 expression in monocytes and triggered LD formation in different human cell lines. LDs were found in close apposition with SARS-CoV-2 proteins and double-stranded (ds)-RNA in infected Vero cells. Electron microscopy (EM) analysis of SARS-CoV-2 infected Vero cells show viral particles colocalizing with LDs, suggestive that LDs might serve as an assembly platform. Pharmacological modulation of LD formation by inhibition of DGAT-1 with A922500 significantly inhibited SARS-CoV-2 replication as well as reduced production of mediators pro-inflammatory response. Taken together, we demonstrate the essential role of lipid metabolic reprograming and LD formation in SARS-CoV-2 replication and pathogenesis, opening new opportunities for therapeutic strategies to COVID-19.

Immune complexes as a tool for strongyloidiasis immunodiagnosis in kidney and liver transplant candidate.

Strongyloidiasis is a chronic and asymptomatic infection in immunocompetent patients. Immunocompromised patients, such as organ transplant candidates, can develop severe forms of this disease, and the best way to prevent progression to these forms is early diagnosis. Serological techniques using specific IgG and immune complexes (IC) detection can help in the diagnosis of these patients. This study aimed to detect specific anti-Strongyloides IC and IgG antibodies in kidney transplant (KT) and liver transplant (LT) candidates. A total of 100 blood samples was collected from transplant candidates (50 blood samples each from KT and LT candidates). Serum was obtained and analysed using enzyme-linked immunosorbent assay for IC and IgG detections. The IC levels showed frequencies of 18% and 2% in the KT and LT groups, respectively, whereas anti-Strongyloides IgG was detected in 34% and 12% of KT and LT candidates, respectively. The correlation between IC and IgG detection is poor in KT candidates, while in LT candidates, there is a significant positive correlation. The detection of IC can be an additional tool for the diagnosis of strongyloidiasis, especially when associated with the detection of specific IgG anti-Strongyloides antibodies.

Knockdown of the inducible nitric oxide synthase (NOS2) splicing variant S3 promotes autophagic cell death from nitrosative stress in SW480 human colon cancer cells.

Low levels of nitric oxide (NO) produced by constitutively expressed inducible NO synthase (NOS2) in tumor cells may be an important factor in their development. NOS2 expression is associated with high mortality rates for various cancers. Alternative splicing of NOS2 down-regulates its enzymatic activity, resulting in decreased intracellular NO concentrations. Specific probes to detect alternative splicing of NOS2 were used in two isogenic human colon cancer cell lines derived either from the primary tumor (SW480) or from a lymph node metastasis (SW620). Splicing variant of NOS2 S3, lacking exons 9, 10, and 11, was overexpressed in SW480 cells. NOS2 S3 was silenced in SW480 cells. Flow-cytometry analysis was used to estimate the intracellular NO levels and to analyze the cell cycle of the studied cell lines. Western blot analysis and quantitative real-time polymerase chain reaction (qRT-PCR) were used to determine apoptosis and autophagy markers. SW480 and SW620 cells expressed NOS2 S3. Overexpression of the NOS2 S3 in SW480 cells downregulated intracellular NO levels. SW480 cells with knocked down NOS2 S3 (referred to as S3C9 cells) had higher intracellular levels of NO compared to the wild-type SW480 cells under serum restriction. Higher NO levels resulted in the loss of viability of S3C9 cells, which was associated with autophagy. Induction of autophagy by elevated intracellular NO levels in S3C9 cells under serum restriction, suggests that autophagy operates as a cytotoxic response to nitrosative stress. The expression of NOS2 S3 plays an important role in regulating intracellular NO production and maintaining viability in SW480 cells under serum restriction. These findings may prove significant in the design of NOS2/NO-based therapies for colon cancer.

Peripheral arterial disease progression and ankle brachial index: a cohort study with newly diagnosed patients with type 2 diabetes.

BACKGROUND: Little is known about the evolution of peripheral arterial disease (PAD) since diagnosis and its association with glycemic and lipid control in patients with Type 2 Diabetes Mellitus (T2DM). OBJECTIVE: Evaluate the actual criteria to start screening PAD with ankle-brachial index (ABI) in T2DM patients and assess its progression and relationship with glycemic and lipid control since diagnosis. METHODS: We performed a 3-year prospective cohort study with two groups: group 1 (978 individuals with T2DM undergoing drug treatment) and group 2 [221 newly diagnosed drug-naive (< 3 months) patients with T2DM]. PAD diagnosis was by ABI ≤ 0.90, regardless any symptoms. RESULTS: As expected, abnormal ABI prevalence was higher in group 1 vs. Group 2 (87% vs. 60%, p < 0.001). However, abnormal ABI prevalence did not differ between patients over and under 50 years in both groups. Our drug-naive group stabilizes ABI (0.9 ± 0.1 vs 0.9 ± 0.1, p = NS) and improved glycemic and lipid control during follow-up [glycated hemoglobin (HbA1c) = 8.9 ± 2.1 vs 8.4 ± 2.3%, p < 0.05; LDL = 132 ± 45 vs 113 ± 38 mg/dL, p < 0.01, respectively]. When compared, patients who evolved with normalization or maintained normal ABI levels at the end [Group A, N = 60 (42%)] with those who decreased ABI to abnormal levels (ABI basal 1.0 ± 0.1 vs final 0.85 ± 0.1, p < 0.001) [Group B, N = 26 (18%)], an improvement in HbA1c (9 ± 2 vs 8 ± 2%, p < 0.05) and a correlation between the final HbA1c with ABI (r = - 0.3, p = 0.01) was found only in the first. In addition, a correlation was found between albuminuria variation and ABI solely in group A (r = - 0.3; p < 0.05). CONCLUSION: Our study suggests that ABI should be measured at diagnosis in T2DM patients, indicating that current criteria to select patients to screen PAD with ABI must be simplified. An improvement in albuminuria and glycemic and lipid control could be related with ABI normalization in newly diagnosed T2DM drug-naive patients.