Salicornia ramosissima Biomass as a Partial Replacement of Wheat Meal in Diets for Juvenile European Seabass (Dicentrarchus labrax).

The green tips of Salicornia ramosissima are used for human consumption, while, in a production scenario, the rest of the plant is considered a residue. This study evaluated the potential of incorporating salicornia by-products in diets for juvenile European seabass, partially replacing wheat meal, aspiring to contribute to their valorization. A standard diet and three experimental diets including salicornia in 2.5%, 5% and 10% inclusion levels were tested in triplicate. After 62 days of feeding, no significant differences between treatments were observed in fish growth performances, feeding efficiency and economic conversation ratio. Nutrient digestibility of the experimental diets was unaffected by the inclusion of salicornia when compared to a standard diet. Additionally, salicornia had significant modulatory effects on the fish muscle biochemical profiles, namely by significantly decreasing lactic acid and increasing succinic acid levels, which can potentially signal health-promoting effects for the fish. Increases in DHA levels in fish fed a diet containing 10% salicornia were also shown. Therefore, the results suggest that salicornia by-products are a viable alternative to partially replace wheat meal in diets for juvenile European seabass, contributing to the valorization of a residue and the implementation of a circular economy paradigm in halophyte farming and aquaculture.

New observations on minifascicular neuropathy with sex-dependent gonadal dysgenesis: a case series with nerve ultrasound assessment.

BACKGROUND: Gonadal dysgenesis with minifascicular neuropathy (GDMN) is a rare autosomal recessive condition associated with biallelic DHH pathogenic variants. In 46, XY individuals, this disorder is characterized by an association of minifascicular neuropathy (MFN) and gonadal dysgenesis, while in 46, XX subjects only the neuropathic phenotype is present. Very few patients with GDMN have been reported so far. We describe four patients with MFN due to a novel DHH likely pathogenic homozygous variant and the results of nerve ultrasound assessment. METHODS: This retrospective observational study included 4 individuals from 2 unrelated Brazilian families evaluated for severe peripheral neuropathy. Genetic diagnosis was performed with a peripheral neuropathy next-generation sequencing (NGS) panel based on whole exome sequencing focused analysis that included a control SRY probe to confirm genetic sex. Clinical characterization, nerve conduction velocity studies, and high-resolution ultrasound nerve evaluation were performed in all subjects. RESULTS: Molecular analysis disclosed in all subjects the homozygous DHH variant p.(Leu335Pro). Patients had a striking phenotype, with marked trophic changes of extremities, sensory ataxia, and distal anesthesia due to a sensory-motor demyelinating polyneuropathy. One 46, XY phenotypically female individual had gonadal dysgenesis. High-resolution nerve ultrasound showed typical minifascicular formation and increased nerve area in at least one of the nerves assessed in all patients. CONCLUSION: Gonadal dysgenesis with minifascicular neuropathy is a severe autosomal recessive neuropathy characterized by trophic alterations in limbs, sensory ataxia, and distal anesthesia. Nerve ultrasound studies are very suggestive of this condition and may help to avoid invasive nerve biopsies.

The effects of flavonoids in experimental sepsis: A systematic review and meta-analysis.

Sepsis is a host's dysregulated immune response to an infection associated with systemic inflammation and excessive oxidative stress, which can cause multiple organ failure and death. The literature suggests that flavonoids, a broad class of secondary plant metabolites, have numerous biological activities which can be valuable in the treatment of sepsis. This study aimed to review the effects of flavonoids on experimental sepsis, focusing mainly on survival rate, and also summarizing information on its mechanisms of action. We searched in the main databases up to November 2022 using relevant keywords, and data were extracted and analyzed qualitatively and quantitatively. Thirty-two articles met the study criteria for review and 29 for meta-analysis. Overall, 30 different flavonoids were used in the studies. The flavonoids were able to strongly inhibit inflammatory response by reducing the levels of important pro-inflammatory mediators, for example, tumor necrosis factor-alpha and interleukin-1ß, oxidative stress, and showed antibacterial and anti-apoptotic actions. The meta-analysis found an increase of 50% in survival rate of the animals treated with flavonoids. They appear to act as multi-target drugs and may be an excellent therapeutic alternative to reduce a number of the complications caused by sepsis, and consequently, to improve survival rate.

Pelagic and estuarine birds as sentinels of metal(loid)s in the South Atlantic Ocean: Ecological niches as main factors acting on bioaccumulation.

Activities related to the offshore exploration and production of oil and natural gas provide economic development and an essential energy source. However, besides the risk of petroleum hydrocarbon contamination, these activities can also be sources of metals and metalloids for marine organism contamination. In this research, we evaluated the potential use of two pelagic (black-browed albatross Thalassarche melanophris and yellow-nosed albatross T. chlororhynchos) and one estuarine bird species (neotropical cormorant Nannopterum brasilianus) as sentinels of contamination of As, Cd, Cr, Cu, Pb, Mn, Mo, Zn, Ni, Ba, V, and Hg in an area under influence of oil and gas activities. The analyses were carried out in samples collected from 2015 to 2022 from 97 individuals. A factor alert; an adaptation from the contamination factor is proposed to identify individuals with high concentrations that possibly suffered contamination by anthropogenic origin. Grouping all species, the metal(loid)s with the highest concentrations were in decreasing order: Zn > Cu > Mn > Hg > As > Cd > Mo > V > Cr > Ba > Ni > Pb. Similar concentrations were observed for V, Mn, Cr and Pb among the three species. Pelagic birds showed higher levels of concentrations for Hg, As and Cd. Based on the correlations and multivariate analysis performed, the results indicate that the ecological niche factor has greater relevance in the bioaccumulation of these elements compared to the habitat. Although some individuals showed high concentrations in part of the trace elements, suggesting exposure to anthropic sources, the direct influence of oil production and exploration activities was not observed, suggesting that activities on the continent are the primary contamination source. The results of this work highlight the role of seabirds as sentinels for metal(loid)s, contributing to the knowledge of the occurrence of contaminants in the South Atlantic Ocean.

Health-Promoting Additives Supplemented in Inert Microdiets for Whiteleg Shrimp (Penaeus vannamei) Post-Larvae: Effects on Growth, Survival, and Health Status.

Dietary additives have the potential to stimulate the whiteleg shrimp immune system, but information is scarce on their use in diets for larval/post-larval stages. The potential beneficial effects of vitamins C and E, ß-glucans, taurine, and methionine were evaluated. Four experimental microdiets were tested: a positive control diet (PC); the PC with decreased levels of vitamin C and E as negative control (NC); the PC with increased taurine and methionine levels (T + M); and the PC supplemented with ß-glucans (BG). No changes in growth performance and survival were observed. However, post-larvae shrimp fed the NC had lower relative expressions of pen-3 than those fed the PC, suggesting that lower levels of vitamins C and E may impact the shrimp immune status. Lipid peroxidation levels dropped significantly in the BG compared to the PC, indicating that ß-glucans improved the post-larvae antioxidant mechanisms. Furthermore, when compared with the NC diet, PL fed with BG showed significant increases in tGSH levels and in the relative expression of crus and pen-3, suggesting a synergistic effect between vitamins C and E and ß-glucans. Amongst the additives tested, ß-glucans seems to be the most promising even when compared to a high-quality control diet.

Exploring the Antioxidant and Genoprotective Potential of Salicornia ramosissima Incorporation in the Diet of the European Seabass (Dicentrarchus labrax).

The identification of novel feed materials as a source of functional ingredients is a topical priority in the finfish aquaculture sector. Due to the agrotechnical practices associated and phytochemical profiling, halophytes emerge as a new source of feedstuff for aquafeeds, with the potential to boost productivity and environmental sustainability. Therefore, the present study aimed to assess the potential of Salicornia ramosissima incorporation (2.5, 5, and 10%), for 2 months, in the diet of juvenile European seabass, seeking antioxidant (in the liver, gills, and blood) and genoprotective (DNA and chromosomal integrity in blood) benefits. Halophyte inclusion showed no impairments on growth performance. Moreover, a tissue-specific antioxidant improvement was apparent, namely through the GSH-related defense subsystem, but revealing multiple and complex mechanisms. A genotoxic trigger (regarded as a pro-genoprotective mechanism) was identified in the first month of supplementation. A clear protection of DNA integrity was detected in the second month, for all the supplementation levels (and the most prominent melioration at 10%). Overall, these results pointed out a functionality of S. ramosissima-supplemented diets and a promising way to improve aquaculture practices, also unraveling a complementary novel, low-value raw material, and a path to its valorization.

Educational Nursing Intervention in Reducing Hospital Readmission and the Mortality of Patients with Heart Failure: A Systematic Review and Meta-Analysis.

(1) Background: Heart failure (HF) represents a public health problem due to its high morbidity and mortality, increased consumption of health resources, prolonged hospitalization, and frequent readmissions. This study was conducted to evaluate the effectiveness of a nursing educational intervention using home visits (HV) combined with telephone contact in reducing hospital readmission and the mortality of patients with HF. (2) Methods: This is systematic review and meta-analysis of randomized controlled trials (RCTs). The databases used were CINAHL, Cochrane, PubMed and SciELO. A gray literature search included Google Scholar, OpenThesis, Clinical trials and reference lists of eligible studies. RCTs of patients diagnosed with HF were included, distributed between the control group (CG) and intervention (IG), in which the IG was submitted to the nursing intervention with HV and telephone contact in association and analyzed the result of readmission and mortality. (3) Results: The search resulted in 2528 articles and, after following steps, 11 remained for final analysis. A total of 1417 patients were analyzed and distributed: 683 in the IG and 734 in the CG. As a primary outcome, the meta-analysis identified a 36% reduction in the risk of readmission [RR 0.64, 95% CI, 0.54−0.75, p < 0.01] and a 35% reduction in mortality in the IG [RR 0.65, 95% CI, 0.50−0.85, p < 0.01]. Heterogeneity was moderate for readmission and homogeneous for mortality. (4) Conclusions: HV and telephone contact are an effective intervention strategy for nurses' educational practice.

Enhancement of the functionality of women with knee osteoarthritis by a gel formulation with Caryocar coriaceum Wittm ("Pequi") nanoencapsulated pulp fixed oil.

Osteoarthritis (OA) is a degenerative joint disease that occurs when there is a change in the mechanical and biological properties of the articular cartilage and the subchondral bone; The condition is more prevalent in women than in men. Pequi oil (PO), which is extracted from the fruits of the pequi tree (Caryocar coriaceum Wittm), is widely used in traditional medicine in the Brazilian northeast for the management of inflammation and joint pain. The aim of this study was to develop a pharmaceutical formulation containing Carbopol® hydrogel nanoencapsulated with pequi pulp fixed oil (PeONC) and evaluate its therapeutic effect on functionality and pain in women with knee osteoarthritis. The study was divided into two stages: Stage 1 - preparation and physico-chemical characterization of the pharmaceutical formulation containing PeONC, cell viability assays and skin irritability testing. Step 2 - A double-blind randomized clinical trial evaluating knee symptoms, quality of life, pressure pain, function, muscle strength and range of motion. The nanoformulation was in a gel form, with a particle size of 209.5 ± 1.06 nm, a pH of 6.23 ± 0.45, a zeta potential of - 23.1 ± 0.4 mV, a polydispersity index of 0.137 ± 0.52, and containing nanocapsules with a spherical shape a polymeric wall and an oily nucleus. The gel showed no cytotoxicity and was not irritating to human skin. The treatment with PeONC increased the strength of the knee flexor and extensor muscles and the total motion range of the knee. In addition, the treatment reduced knee instability, pain, swelling, and locking; There was also an improvement in some items of the SF-36 quality of life questionnaire such as in respect of functional capacity and social aspects. In conclusion, PeONC was found to be a stable, safe formulation with no toxicity in respect of topical use in humans. Additionally, the treatment produced an increase in muscle strength and functionality that was associated with reduced knee symptoms and improved quality of life. Our findings showed that in a group of women treated with PeONC mitigated the symptoms of knee osteoarthritis.

Nerolidol attenuates isoproterenol-induced acute myocardial infarction in rats.

Cardiovascular diseases have high morbidity and mortality rates, and their treatment is not effective in reducing the damage caused by myocardial infarction (MI). This study aimed to investigate whether nerolidol (NRD), a sesquiterpene alcohol, could attenuate MI in an isoproterenol-treated rat model. MI was induced by the administration of two doses of isoproterenol (ISO, 100 mg/kg, i.p.) with an interval of 24 h between doses.The animals were divided into four groups: control (CTR) (vehicle - NaCl 0.9% + Tween 80 0.2%), MI (ISO + vehicle), MI + NRD (50 mg/kg) and MI + NRD (100 mg/kg). An electrocardiogram was performed, and contractile parameters, cardiac enzymes, infarction size, and antioxidant parameters in the heart were measured to evaluate the effects of NRD. The ISO group showed a significant rise in ST segment, QTc, and heart rate associated with a reduction in left ventricular developed pressure (LVDP), + dP/dt, and -dP/dt. In addition, there were increases in levels of creatine kinase (CK), creatine kinase-myocardial band (CK-MB), lactate dehydrogenase (LDH), and thiobarbituric acid (TBARS); reductions in superoxide dismutase (SOD) and catalase (CAT) activities; and an increase in the infarction size. Interestingly, NRD significantly attenuated almost all the parameters of ISO-induced MI mentioned above. Our results suggest that nerolidol attenuates MI caused by ISO by a marked reduction in myocardial infarct size and suppression of oxidative stress. CK total, creatine kinase total; CK-MB, creatine kinase myocardial band; LDH, lactate dehydrogenase; SOD, superoxide dismutase; CAT, catalase. CTR (vehicle group), MI (100 mg/kg of isoproterenol), ISO + NRD 50 (50 mg/kg of nerolidol), and ISO + NRD 100 (100 mg/kg of nerolidol).

Metals and metalloids in green turtle hepatic tissue (Chelonia mydas) from Santos Basin, Brazil.

Metal and metalloid concentrations in the liver tissue of green turtles (Chelonia mydas) stranded on the Brazilian coast (n = 506) were studied using inductively coupled plasma mass spectrometry and cold vapor atomic fluorescence spectrometry. The influences of occurrence registers (date and location) and biological characteristics (sex, age, and developmental stage) were assessed, as well as the temporal influences of oil exploration and production activities. The mean concentrations of Cd, Cu, Mn, Zn, and Hg were the highest reported for the liver of C. mydas on the Brazilian coast. The mean element concentrations followed the order: Cu > Zn > Cd > Mn > As > Hg > Mo > Pb > V > Ni > Ba > Cr. Further, significant differences (p < 0.05) were observed for Hg between the sexes (males > females) and for As, Cu, Pb, Mo, and V between young individuals and older individuals (≥11 years), suggesting a relationship between the dietary shift inherent to green turtle development. These results were corroborated by the curved carapace length (CCL) data, wherein individuals residing in coastal areas (CCL > 50 cm) presented higher concentrations of Cu, Pb, Mo, Zn, Ba, and V than those in the oceanic stage (CCL < 30 cm). The opposite pattern was observed for As and Hg. The influences of spatial autocorrelation (Moran Index) at a global scale and oil production activities on the element concentrations were not observed. However, five hotspots of high metal concentrations were identified via a local spatial autocorrelation (local indicator of spatial association), existing predominantly in a region of heavy anthropic activity within the sampling area. Further, baseline element concentrations were established at the 95% confidence level. Overall, the developmental stage, which is related to feeding habits, had an expressive influence on element concentrations.

Dizziness is a predictor factor for the risk of falls in institutionalised older adults in Brazil.

Considering the small number of studies aimed at evaluating outcomes related to dizziness and falls in the older adults who live in long-term care facilities, especially in north-eastern Brazil, and considering the negative impact of these events on the quality of life of these individuals, this study purpose was to evaluate dizziness as a predictor of risk of falls in institutionalised older adults. This cross-sectional analysis of data on falls and dizziness of 187 institutionalised older adults carried out between the years 2014 and 2016. The data collection instruments used were a socioeconomic and demographic questionnaire and questionnaires for assessing variables related to falls. The different diagnostic methods were compared using the Spearman correlation, and the Dizziness variable was evaluated by means of logistic regression. Inferential statistical analysis showed a significant association between dizziness and number of morbidities (p = .03) and dizziness and a history of falls (p = .04). Spearman's correlation analysis revealed statistically significant results only for FES-I (Falls Efficacy Scale-International) (p < .01). Dizziness was a predictor of risk of falls and that it was associated with a greater number of morbidities and previous history of falls. Implementing rehabilitation practices to reduce dizziness symptoms can significantly reduce the risk of falls for institutionalised older adults.

Morphometric vertebral fracture risk in women with postsurgical hypoparathyroidism.

Introduction: Hypoparathyroidism (HP) is a rare endocrine disease and there are little data available on the risk of fragility fractures in these patients. PTH deficiency results in a positive bone balance with higher bone mass in all skeletal sites. However, whether these structural and dynamic skeletal changes have a negative impact on the fracture risk, it is not known. Methods: Aiming to investigate the risk of insufficiency vertebral fractures in HP, defined using morphometric criteria, a consecutive sampling of 44 women with chronic postsurgical HP was compared to a control group of 44 adult healthy women, matched by age with patients. Vertebral fractures were analyzed by the semiquantitative Genant's method followed by quantitative vertebral morphometry. Results: Morphometric vertebral fractures were identified in 5/44 (11.4%) patients and in 3/44 (6.8%) controls (p=0.731). Most fractures were classified as Genant II and III grades in HP patients, whereas most were Genant I in controls. A logistic regression multivariate analysis was conducted in which age, BMI and parathyroid status were the independent variables, and morphometric vertebral fracture was the dependent variable, but none of these factors was a significant predictor of fracture in this population (OR 1.01, 95% CI 0.96-1.07, p=0.634 for age; OR 2.24, 95%CI 0.47-10.50, p=0.306 for the presence/absence of HP and OR 0.92, 95% CI 0.76-1.10, p=0.369 for BMI). Conclusion: The results of this study cannot ensure a higher risk of fragility vertebral fractures in postsurgical HP patients. Instead, we only observed higher Genant grade classification of the deformed vertebrae in our sample.

Resistance training increases insulin-induced vasodilation in the mesenteric artery of healthy rats.

This study evaluated the ability of resistance training (RT) of moderate intensity to promote vascular changes in insulin-induced vasodilation in healthy animals. Wistar rats were divided into two groups: control (CON) and trained (eight weeks of training, performing 3 sets with 10 repetitions at 60% of maximum intensity). Forty-eight hours after the last session of the RT, the animals were sacrificed and vascular reactivity to insulin in the absence and presence of LY294002 (phosphatidylinositol 3-kinase inhibitors (PI3K), L-NAME (nitric oxide synthase (NOS) inhibitors) and BQ123 (endothelin A antagonist (ET-A) receptor). In addition, phenylephrine (Phe)-induced vasoconstriction in the absence and presence of L-NAME was also evaluated. The RT group showed greater vasodilation in maximal response compared to the CON group. After PI3K inhibition, vasodilation was reduced in both groups. However, when the NOS participation was evaluated, the RT group showed contraction in relation to the CON group, which was abolished by BQ123. In addition, the RT group had an increase in nitrite levels compared to the CON group. When the Phe response was evaluated, there was a reduction in tension in the RT group compared to the CON group. The results suggest that RT improves vascular reactivity.

Wound healing properties of flavonoids: A systematic review highlighting the mechanisms of action.

BACKGROUND: Flavonoids are a class of compounds with a wide variety of biological functions, being an important source of new products with pharmaceutical potential, including treatment of skin wounds. PURPOSE: This review aimed to summarize and evaluate the evidence in the literature in respect of the healing properties of flavonoids on skin wounds in animal models. STUDY DESIGN: This is a systematic review following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. METHODS: This was carried out through a specialized search of four databases: PubMed, Scopus, Web of Science and Embase. The following keyword combinations were used: "flavonoidal" OR "flavonoid" OR "flavonoidic" OR "flavonoids" AND "wound healing" as well as MeSH terms, Emtree terms and free-text words. RESULTS: Fifty-five (55) articles met the established inclusion and exclusion criteria. Flavonoids presented effects in respect of the inflammatory process, angiogenesis, re-epithelialization and oxidative stress. They were shown to be able to act on macrophages, fibroblasts and endothelial cells by mediating the release and expression of TGF-ß1, VEGF, Ang, Tie, Smad 2 and 3, and IL-10. Moreover, they were able to reduce the release of inflammatory cytokines, NFκB, ROS and the M1 phenotype. Flavonoids acted by positively regulating MMPs 2, 8, 9 and 13, and the Ras/Raf/MEK/ERK, PI3K/Akt and NO pathways. CONCLUSION: Flavonoids are useful tools in the development of therapies to treat skin lesions, and our review provides a scientific basis for future basic and translational research.

Neonatal Subpial Hemorrhage: Clinical Factors, Neuroimaging, and Outcomes in a Quaternary Care Children's Center.

BACKGROUND: Subpial hemorrhages are underrecognized, underreported, and poorly understood. The spectrum of their clinical manifestations and consequences in neonates has not been fully described. Here, we describe the demographic, clinical, and radiographic characteristics of neonates with subpial hemorrhages. METHODS: We reviewed the medical records and neuroimaging studies of neonates with subpial hemorrhage who were admitted to our neonatal intensive care unit between September 2009 and December 2020. RESULTS: Of 114 neonates with intracranial hemorrhage, 31 (27%) had subpial hemorrhage. The majority of neonates in our cohort were male (68%) and born at term (55%). The most common imaging indication was apneas and/or seizures in 58%. Common comorbid conditions included cardiorespiratory failure (42%), hypoxic-ischemic encephalopathy (26%), and coagulopathy (23%). Subpial hemorrhages were multifocal in 45% of neonates, located in the temporal lobe in 45% of neonates, and tended to be larger in neonates with coagulopathy, birth trauma, or hydrocephalus requiring neurosurgical intervention. Subpial hemorrhage was associated with another type of intracranial bleed in 77% of cases and with arterial ischemic stroke in 16% of cases. Of 17 patients with more than one year of follow-up data, 14 (82%) have developmental delay and four (24%) have epilepsy. Of 14 patients with follow-up imaging, 10 (71%) had encephalomalacia subjacent to the subpial hemorrhage. CONCLUSIONS: This is the largest cohort of neonates with subpial hemorrhages to date. Outcome data are limited by duration of follow-up and may be confounded by comorbid conditions and other concurrent hemorrhages. Further study is needed to define the spectrum of risk factors and expected neurological outcomes.

Cardiovascular effects of farnesol and its ß-cyclodextrin complex in normotensive and hypertensive rats.

Farnesol (FAR) is a sesquiterpene alcohol with a range of reported biological effects including cardioprotective, antioxidant and antiarrhythmic properties. However, due to its volatility, the use of drug incorporation systems, such as cyclodextrins, have been proposed to improve its pharmacological properties. Thus, the aim of this study was to evaluate and characterize the cardiovascular effects of FAR alone, and to investigate the antihypertensive effects of FAR complexed with ß-cyclodextrin (ßCD) in rats. Mean arterial pressure (MAP) and heart rate (HR) were measured before and after intravenous administration of FAR (0,5; 2,5; 5 and 7,5 mg/kg) in normotensive rats, and after oral acute administration (200 mg/kg) of FAR and FAR/ßCD complex in NG-nitro-L-arginine-methyl-ester (L-NAME) hypertensive rats. In normotensive animals, FAR induced dose-dependent hypotension associated with bradycardia. These effects were not affected by pre-treatment with L-NAME or indomethacin (INDO), but were partially attenuated by atropine. Pre-treatment with hexamethonium (HEXA) only affected hypotension. In the hypertensive rats, FAR/ßCD potentialized the antihypertensive effect when compared to FAR alone. Molecular docking experiments demonstrated for the first time that FAR has affinity to bind to the M3 and M2 muscarinic, and nicotinic receptors through hydrogen bonds in the same residues as known ligands. In conclusion, our results demonstrated that FAR induced hypotension associated with bradycardia, possibly through the muscarinic and nicotinic receptors. The inclusion complex with ßCD improved the antihypertensive effects of FAR, which can be relevant to improve current cardiovascular therapy using volatile natural components.

Immersive virtual reality is effective in the rehabilitation of older adults with balance disorders: A randomized clinical trial.

QUESTION: What are the effects of immersive virtual reality (IVR) training compared to conventional physiotherapy on body balance and risk of falls in older adults with balance disorders? DESIGN: A randomized controlled trial with two intervention arms, concealed allocation, per-protocol analysis, and blinded assessment. PARTICIPANTS: Thirty-seven older adults with balance disorders and risk of falling. INTERVENTION: Participants were randomized into two groups: a control group, which received balance training with conventional physiotherapy using multimodal circuit exercises, and an experimental group, which received balance training using immersive virtual reality. Both groups received 16 individual sessions, twice a week. OUTCOME MEASURES: The primary outcome was functional balance. Secondary outcomes were static balance, gait speed, functional range, dizziness symptoms, and fear of falling. Safety was ensured by assessing any adverse events during the intervention. RESULTS: After 16 sessions, in the intragroup analysis, the functional balance score in the experimental group increased by 3.00 (95% CI 1.42 to 4.57) and in the control group by 3.88 (95% CI 2.16 to 5.59). Both groups improved in assessments of sensory interaction and anterior reach. Only the experimental group presented increased mobility and reduced dizziness. After two months, there was a maintenance of gains in functional balance and a reduction of the gains in functional reach for both groups. In the intergroup comparison, there was no significant difference. CONCLUSION: Immersive Virtual Reality training proved to be effective for balance-related outcomes, although it was not superior to conventional therapy. TRIAL REGISTRATION: RBR-3tk7fw.

Insights into the actions of angiotensin-1 receptor (AT1R) inverse agonists: Perspectives and implications in COVID-19 treatment.

New coronavirus SARS-CoV-2 (COVID-19) has caused chaos in health care systems. Clinical manifestations of COVID-19 are variable, with a complex pathophysiology and as yet no specific treatment. It has been suggested that the renin-angiotensin-aldosterone system has a possible role in the severity of cases and the number of deaths. Our hypothesis is that drugs with inverse agonist effects to the angiotensin-1 receptor can be promising tools in the management of patients with COVID-19, possibly avoiding complications and the poor evolution in some cases. Any risk factors first need to be identified, and the most appropriate time to administer the drugs during the course of the infection also needs to be established. Several angiotensin receptor blockers (ARB) have a favorable profile and are important candidates for the treatment of COVID-19. In this review we discussed a set of compounds with favorable profile for COVID-19 treatment, including azilsartan, candesartan, eprosartan, EXP3174, olmesartan, telmisartan, and valsartan. They are effective as inverse agonists and could reduce the "cytokine storm" and reducing oxidative stress. As COVID-19 disease has several evolution patterns, the effectiveness of ARB therapy would be related to infection "timing", patient risk factors, previous use of ARBs, and the specific molecular effects of an ARB. However, controlled studies are needed to identify whether ARBs are beneficial in the treatment of patients with COVID-19.

Intraspecific variation of trace elements in the kelp gull (Larus dominicanus): influence of age, sex and location.

Hepatic tissue of Larus dominicanus sampled on the coastline of the state of Santa Catarina in Brazil between October 2016 and May 2018 was used to evaluate intraspecific trends and spatial distribution of essential trace elements (Mn, Co, Cu, Zn, Mo and Cr) and non-essential trace elements (As, Pb, Cd, Hg, Ba and V). Principal Component Analysis (PCA) indicated differences in the bioaccumulation of trace elements between female adults and male adults, differences to sex and age were indicated by Kruskal-Wallis test. Heat maps suggest hot spots in locals with high concentration of trace elements in liver of Larus dominicanus. In general, the concentration of trace elements were comparable with values reported in other studies carried out for this species in South America and other regions of the world. The heat maps showed to be a promising tool to identify influences of the locality on bioaccumulation of trace elements in Larus dominicanus.

New machine learning and physics-based scoring functions for drug discovery.

Scoring functions are essential for modern in silico drug discovery. However, the accurate prediction of binding affinity by scoring functions remains a challenging task. The performance of scoring functions is very heterogeneous across different target classes. Scoring functions based on precise physics-based descriptors better representing protein-ligand recognition process are strongly needed. We developed a set of new empirical scoring functions, named DockTScore, by explicitly accounting for physics-based terms combined with machine learning. Target-specific scoring functions were developed for two important drug targets, proteases and protein-protein interactions, representing an original class of molecules for drug discovery. Multiple linear regression (MLR), support vector machine and random forest algorithms were employed to derive general and target-specific scoring functions involving optimized MMFF94S force-field terms, solvation and lipophilic interactions terms, and an improved term accounting for ligand torsional entropy contribution to ligand binding. DockTScore scoring functions demonstrated to be competitive with the current best-evaluated scoring functions in terms of binding energy prediction and ranking on four DUD-E datasets and will be useful for in silico drug design for diverse proteins as well as for specific targets such as proteases and protein-protein interactions. Currently, the MLR DockTScore is available at www.dockthor.lncc.br .