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Sepsis is associated with marked alterations in hemodynamic responses, autonomic dysfunction and impaired vascular function. However, to our knowledge, analysis of noninvasive markers to identify greater risk of death has not yet been investigated. Thus, our aim was to explore the prognostic utility of cardiac output (CO), stroke volume (SV), indices of vagal modulation (RMSSD and SD1), total heart rate variability (HRV) indices and FMD of brachial artery (%FMD), all measured noninvasively, in the first 24 hours of the diagnosis of sepsis. 60 patients were recruited at ICU between 2015 and 2017 and followed by 28 days. CO, SV, RR intervals were measurement. Doppler ultrasound was used to assess brachial artery FMD and the hyperemic response were obtained (%FMD). Patients were divided by survivors (SG) and nonsurvivors groups (NSG). A total of 60 patients were analysed (SG = 21 and NSG = 39). Survivors were younger (41±15 years vs. 55±11 years) and used less vasoactive drugs. As expected, APACHE and SOFA scores were lower in NSG compared to SG. In addition, higher SD1, triangular index, % FMD, velocity baseline and hyperemia flow velocity as well as lower HR values were observed in the SG, compared to NSG (P<0.05). Interestingly, RMSSD and SD1 indices were independent predictors of %FMD, ΔFMD and FMDpeak. RMSSD threshold of 10.8ms and %FMD threshold of -1 were optimal at discriminatomg survivors and nonsurvivors. Noninvasive measurements of autonomic and endotelial function may be important markers of sepsis mortality, which can be easily obtained in the early stages of sepsis at the bedside.

Background Intensive care unit-acquired atrophy and weakness are associated with high mortality, a reduction in physical function, and quality of life. Passive mobilization (PM) and neuromuscular electrical stimulation were applied in comatose patients; however, evidence is inconclusive regarding atrophy and weakness prevention. Blood flow restriction (BFR) associated with PM (BFRp) or with electrical stimulation (BFRpE) was able to reduce atrophy and increase muscle mass in spinal cord-injured patients, respectively. Bulky venous return occurs after releasing BFR, which can cause unknown repercussions on the cardiovascular system. Hence, the aim of this study was to investigate the effect of BFRp and BFRpE on cardiovascular safety and applicability, neuromuscular adaptations, physical function, and quality of life in comatose patients in intensive care units (ICUs). Methods Thirty-nine patients will be assessed at baseline (T0–18 h of coma) and randomly assigned to the PM (control group), BFRp, or BFRpE groups. The training protocol will be applied in both legs alternately, twice a day with a 4-h interval until coma awake, death, or ICU discharge. Cardiovascular safety and applicability will be evaluated at the first training session (T1). At T0 and 12 h after the last session (T2), muscle thickness and quality will be assessed. Global muscle strength and physical function will be assessed 12 h after T2 and ICU and hospital discharge for those who wake up from coma. Six and 12 months after hospital discharge, physical function and quality of life will be re-assessed. Discussion In view of applicability, the data will be used to inform the design and sample size of a prospective trial to clarify the effect of BFRpE on preventing muscle atrophy and weakness and to exert the greatest beneficial effects on physical function and quality of life compared to BFRp in comatose patients in the ICU. Trial registration Universal Trial Number (UTN) Registry UTN U1111-1241-4344. Retrospectively registered on 2 October 2019. Brazilian Clinical Trials Registry (ReBec) RBR-2qpyxf . Retrospectively registered on 21 January 2020, http://ensaiosclinicos.gov.br/rg/RBR-2qpyxf/

Sepsis is a serious organ dysfunction leading to endothelial damage in critical patients. Physiologically, there is an augment of vascular diameter in response to increased vascular blood flow and shear stress stimulus. However, the pattern of vascular response in face of passive mobilization (PM), an early mobilization physical strategy, has not yet been explored in patients with sepsis. To explore patterns of vascular response to PM and associations with clinical and cardiovascular profile in patients with sepsis. Cross-sectional, single-arm study. Thirty-two patients diagnosed with sepsis were enrolled. Vascular response was assessed by flow-mediated dilation (FMD) using brachial artery ultrasound, before and after PM. The PM (to assess the response pattern) and SR (shear rate) were also calculated. PM protocol consisted of knees, hips, wrists, elbows, shoulders, dorsiflexion/plantar flexion movements 3 × 10 repetitions each (15 min). Arterial stiffness was assessed by Sphygmocor®, by analyzing the morphology and pulse wave velocity. Cardiac autonomic modulation (CAM) was assessed by analyzing heart rate variability indexes (mean HR, RMSSD, LF, HF, ApEn, SampEn, DFA). Different vascular responses were observed after PM: (1) increased vascular diameter (responders) (n = 13, %FMD = 11.89 ± 5.64) and (2) reduced vascular diameter (non-responders) (n = 19, %FMD= −7.42 ± 6.44). Responders presented a higher non-linear DFA2 index (p = 0.02). There was a positive association between FMD and DFA (r = 0.529; p = 0.03); FMD and SampEn (r = 0.633; p < 0.01). A negative association was identified between FMD and LF (Hz) (r= −0.680; p < 0.01) and IL-6 (r= −0.469; p = 0.037) and SR and CRP (r= −0.427; p = 0.03).

Leishmania RNA virus (LRV) is an important virulence factor associated with the development of mucocutaneous Leishmaniasis, a severe form of the disease. LRV-mediated disease exacerbation relies on TLR3 activation, but downstream mechanisms remain largely unexplored. Here, we combine human and mouse data to demonstrate that LRV triggers TLR3 and TRIF to induce type I IFN production, which induces autophagy. This process results in ATG5-mediated degradation of NLRP3 and ASC, thereby limiting NLRP3 inflammasome activation in macrophages. Consistent with the known restricting role of NLRP3 for Leishmania replication, the signaling pathway triggered by LRV results in increased parasite survival and disease progression. In support of this data, we find that lesions in patients infected with LRV+ Leishmania are associated with reduced inflammasome activation and the development of mucocutaneous disease. Our findings reveal the mechanisms triggered by LRV that contribute to the development of the debilitating mucocutaneous form of Leishmaniasis. NLRP3 activation by Leishmania parasites is critical to the outcome of the disease. Here the authors show that LRV, a virus infecting Leishmania strains associated with more severe human disease, enables the parasite to suppress the inflammasome by activating type 1 interferon through TLR3, which leads to autophagy-mediated NLRP3 degradation.

The SARS-CoV-2 entry into host cells is mainly mediated by the interactions between the viral spike protein (S) and the ACE-2 cell receptor, which are highly glycosylated. Therefore, carbohydrate binding agents may represent potential candidates to abrogate virus infection. Here, we evaluated the in vitro anti-SARS-CoV-2 activity of two mannose-binding lectins isolated from the Brazilian plants Canavalia brasiliensis and Dioclea violacea (ConBR and DVL). These lectins inhibited SARS-CoV-2 Wuhan-Hu-1 strain and variants Gamma and Omicron infections, with selectivity indexes (SI) of 7, 1.7, and 6.5, respectively for ConBR; and 25, 16.8, and 22.3, for DVL. ConBR and DVL inhibited over 95% of the early stages of the viral infection, with strong virucidal effect, and also protected cells from infection and presented post-entry inhibition. The presence of mannose resulted in the complete lack of anti-SARS-CoV-2 activity by ConBR and DVL, recovering virus titers. ATR-FTIR, molecular docking, and dynamic simulation between SARS-CoV-2 S and either lectins indicated molecular interactions with predicted binding energies of −85.4 and −72.0 Kcal/Mol, respectively. Our findings show that ConBR and DVL lectins possess strong activities against SARS-CoV-2, potentially by interacting with glycans and blocking virus entry into cells, representing potential candidates for the development of novel antiviral drugs.

Alzheimer’s and Parkinson’s diseases are considered the most common neurodegenerative disorders, representing a major focus of neuroscience research to understanding the cellular alterations and pathophysiological mechanisms involved. Several natural products, including flavonoids, are considered able to cross the blood-brain barrier and are known for their central nervous system-related activity. Therefore, studies are being conducted with these chemical constituents to analyze their activities in slowing down the progression of neurodegenerative diseases. The present systematic review summarizes the pharmacological effects of flavonoids in animal models for Alzheimer’s and Parkinson’s diseases. A PRISMA model for systematic review was utilized for this search. The research was conducted in the following databases: PubMed, Web of Science, BIREME, and Science Direct. Based on the inclusion criteria, 31 articles were selected and discussed in this review. The studies listed revealed that the main targets of action for Alzheimer’s disease therapy were reduction of reactive oxygen species and amyloid beta-protein production, while for Parkinson’s disease reduction of the cellular oxidative potential and the activation of mechanisms of neuronal death. Results showed that a variety of flavonoids is being studied and can be promising for the development of new drugs to treat neurodegenerative diseases. Moreover, it was possible to verify that there is a lack of translational research and clinical evidence of these promising compounds.

Data regarding the use and effect of hormonal contraceptives on bone mass acquisition during adolescence are contradictory. The present study was designed to evaluate bone metabolism in two groups of healthy adolescents using combined oral contraceptives (COC). A total of 168 adolescents were recruited from 2014 to 2020 in a non-randomized clinical trial and divided into three groups. The COC1 group used 20 μg Ethinylestradiol (EE)/150 μg Desogestrel and the COC2 group used 30 μg EE/3 mg Drospirenone over a period of two years. These groups were compared to a control group of adolescent non-COC users. The adolescents were submitted to bone densitometry by dual-energy X-ray absorptiometry and measurement of bone biomarkers, bone alkaline phosphatase (BAP), and osteocalcin (OC) at baseline and 24 months after inclusion in the study. The three groups studied were compared at the different time points by ANOVA, followed by Bonferroni's multiple comparison test. Incorporation of bone mass was greater in non-users at all sites analyzed (4.85 g in lumbar Bone mineral content (BMC)) when compared to adolescents of the COC1 and COC2 groups, with a respective increase of 2.15 g and loss of 0.43g in lumbar BMC (P = 0.001). When comparing subtotal BMC, the control increased 100.83 g, COC 1 increased 21.46 g, and COC 2 presented a reduction of 1.47 g (P = 0.005). The values of bone markers after 24 months are similar for BAP, being 30.51 U/L (± 11.6) for the control group, 34.95 U/L (± 10.8) for COC1, and 30.29 U/L for COC 2 (± 11.5) (P = 0.377). However, when we analyzed OC, we observed for control, COC 1, and COC 2 groups, respectively, 13.59 ng/mL (± 7.3), 6.44 ng/mL (± 4.6), and 9.48 ng/mL (± 5.9), with P = 0.003. Despite loss to follow-up occurring in the three groups, there were no significant differences between the variables in adolescents at baseline who remained in the study during the 24-month follow-up and those who were excluded or lost to follow-up. Bone mass acquisition was compromised in healthy adolescents using combined hormonal contraceptives when compared to controls. This negative impact seems to be more pronounced in the group that used contraceptives containing 30 μg EE. http://www.ensaiosclinicos.gov.br, RBR-5h9b3c. \"Low-dose combined oral contraceptive use is associated with lower bone mass in adolescents\".

The traffic in international animal products can become a public health hazard when legal import sanitary procedures are not followed. In Brazil, due to its extensive border area, the importation of animal products is a common practice in many areas, especially in Rio Grande do Sul, a state that borders Argentina and Uruguay. The objective of this study was to evaluate the presence of veterinary drug residues (antibiotics and antiparasitics) in animal products consumed in Rio Grande do Sul. The presence of residues of veterinary antibiotics and antiparasitics was assessed in 189 meat (beef, pork, and chicken), processed dairy, and meat product samples bought in Argentina (n = 90) and Uruguay (n = 99). Residues of these veterinary drugs were detected in 50 (26.45%) of the samples; 28 samples (14.81%) had antibiotic residues, and 22 samples (11.64%) had antiparasitic residues. Of the 50 positive samples, 40% (15 from Argentina and 5 from Uruguay) had residues above the maximum residue limits (MRLs). Of these 20 samples, 12 had antiparasitic residues above the MRLs (11 beef samples had ivermectin and 1 pork sample had ivermectin and doramectin) and 8 had antibiotic residues above the MRLs (2 pork and 2 sausage samples had doxycycline, 2 cheese samples had doxycycline and chlortetracycline, 1 poultry meat sample had chloramphenicol, and 1 cheese sample had monensin). Because of the potential toxic effects on humans and the potential for pathogens to develop antibiotic resistance, the presence of these residues above the MRLs is a potential risk to public health. The negative impact of consumption of imported animal products can be reduced by implementation of an effective surveillance system and educational campaigns for the general population.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.An amendment to this paper has been published and can be accessed via a link at the top of the paper.