Endoscopic and External Dacryocystorhinostomy: Long Term Result from a Tertiary Center in Portugal.

Dacryocystorhinostomy is the gold-standard for distal lacrimal obstructions. This study aims to report the demography, clinical presentation, influence of agger nasi opening, uncinectomy and septoplasty, the use of silicone stent tubes, complications and success of endoscopic and external dacryocystorhinostomy over a period of 11 years. Retrospective review of clinical records, from January 2012 to December 2022, at a tertiary center in Portugal. A total of 249 procedures, 6 external and 243 endoscopic, were performed, including 39 revision cases. There was a female predominance (79.9%) with a mean age at diagnosis of 66.4 years. Recurrent acute dacryocystitis, reported by 33.3%, was associated with higher success (p = 0.053). Agger nasi opening, uncinectomy and septoplasty were performed in 17.7%, 6.0% and 15.3% respectively, although associated with higher success rates, no statistically significant difference was found. Minor complication rates for both external and endoscopic approach was 33.3% and 32.1% respectively. Functional and anatomical success was 100% and 83.3%, respectively, for external dacryocystorhinostomy, and 91.4% and 85.1%, respectively, for endoscopic dacryocystorhinostomy. Revision surgery was associated with a worse anatomical success (p = 0.05). Endoscopic dacryocystorhinostomy is an effective and safe alternative to the external approach. Minor procedures can increase the success rate, but multicentre studies need to be performed for a statistically significant result.

Dietary glycemic and energy load differentially modulates Schistosoma mansoni-induced granulomatous inflammation and response to antiparasitic chemotherapy.

The impact of diet composition and energy content on schistosomiasis evolution and treatment efficacy is still controversial. This study compared the impact of sucrose-rich diet and intermittent fasting on Schistosoma mansoni infection and praziquantel (PZQ)-based chemotherapy response in mice. BALB/c mice were infected with S. mansoni and followed for 15 weeks. The animals were randomized into nine groups receiving high glycemic load (high-sucrose diet - HSD), low caloric load (standard chow alternate-day fasting - ADF), and standard chow ad libitum (AL). Eight weeks after S. mansoni infection, these groups remained untreated or were treated with PZQ (300 mg/kg/day) for 3 days. Our results indicated that parasite load (S. mansoni eggs and parasite DNA levels), granulomatous inflammation (granulomas number and size), and liver microstructural damage (reduction in hepatocytes number, increase in nucleus-cytoplasm ratio, connective stroma expansion and fibrosis) were increased in ADF-treated animals. These animals also showed decreased eggs retention, granulomatous inflammation and collagen accumulation in the small intestine. Conversely, HSD diet and PZQ treatment attenuated all these parameters and stimulated hepatic regenerative response. PZQ also stimulated fibrosis resolution in HSD-treated mice, effect that was limited ADF-exposed mice. Our findings indicate that dietary glycemic and energy load can modulate schistosomiasis progression and the severity of hepatic and intestinal granulomatous inflammation in untreated and PZQ-treated mice. Thus, lower intestinal eggs retention may potentially be linked to worsening liver disease in ADF, while attenuation of hepatic and intestinal granulomatous inflammation is consistent with reduced parasite load in HSD- and PZQ-treated animals.

Bone cement in ossicular chain reconstruction: systematic review and meta-analysis.

OBJECTIVES: To compare the hearing outcomes of ossicular chain reconstruction using bone cement versus other materials such as prostheses and autografts. METHODS: This study included articles that compared hearing outcomes in patients with conductive hearing loss who underwent stapes revision surgery or chronic otitis media surgery. A systematic search for articles from January 2000 to February 2022 was conducted in Medline, Embase, and Cochrane Library databases. Only articles in English were included. An effective postoperative air-bone gap (ABG) was defined as ≤20 dB. A bias assessment tool was developed according to Cochrane guidelines, and the chi-square test was used to evaluate the mean age of the samples. RESULTS: Of the 418 studies that met the selection criteria, only seven were eligible for this study, consisting of 187 patients in the bone cement group and 173 in the non-bone cement group. Ossiculoplasty using bone cement yielded significantly better results, with a combined odds ratio (OR) of 2.03 (95% CI: 1.16-3.55, p = 0.01). CONCLUSIONS: The results of this study suggest that the effectiveness of bone cement in ossiculoplasty was greater than that of other materials in chronic otitis media surgery or stapes revision surgery, with a higher number of patients achieving ABG ≤20 dB.

Neonatal treatment with para-chlorophenylalanine (pCPA) induces adolescent hyperactivity associated with changes in the paraventricular nucleus Crh and Trh expressions.

Disruption of the brain serotoninergic (5-HT) system during development induces long-lasting changes in molecular profile, cytoarchitecture, and function of neurons, impacting behavioral regulation throughout life. In male and female rats, we investigate the effect of neonatal tryptophan hydroxylase (TPH) inhibition by using para-chlorophenylalanine (pCPA) on the expression of 5-HTergic system components and neuropeptides related to adolescent social play behavior regulation. We observed sex-dependent 5-HT levels decrease after pCPA-treatment in the dorsal raphe nucleus (DRN) at 17 and 35 days. Neonatal pCPA-treatment increased playing, social and locomotory behaviors assessed in adolescent rats of both sexes. The pCPA-treated rats demonstrated decreased Crh (17 days) and increased Trh (35 days) expression in the hypothalamic paraventricular nucleus (PVN). There was sex dimorphism in Htr2c (17 days) and VGF (35 days) in the prefrontal cortex, with the females expressing higher levels of it than males. Our results indicate that neonatal pCPA-treatment results in a long-lasting and sex-dependent DRN 5-HT synthesis changes, decreased Crh, and increased Trh expression in the PVN, resulting in a hyperactivity-like phenotype during adolescence. The present work demonstrates that the impairment of TPH function leads to neurobehavioral disorders related to hyperactivity and impulsivity, such as attention deficit hyperactivity disorder (ADHD).

Association Between the Length of Leukocyte Telomeres and Functional Performance of Older Adults: Observational Study.

Despite current literature pointing to a link between shortened telomeres and aging, chronic diseases, and geriatric syndromes, the precise implications of this connection remain unclear. The aim of this exploratory, cross-sectional, observational study was to investigate the association between the relative telomere length (RTL) of peripheral blood leukocyte subtypes (mononuclear cells and granulocytes) and physical performance using the Short Physical Performance Battery (SPPB) in older adults. A cohort of 95 participants was recruited, which included men and women aged over 60 years (70.48 ± 5.5 years). It was found that mononuclear cell RTL was significantly lower than that of granulocytes (p < 0.0001). Moreover, individuals with good SPPB performance exhibited lower mononuclear cell RTL compared with those with moderate or poor performance. However, no significant differences were observed in granulocyte RTL between different SPPB performance groups. The global SPPB score showed an inverse correlation with mononuclear cell RTL, but this correlation was not present with granulocyte RTL. Similarly, the SPPB sit-to-stand domain correlated with mononuclear cell RTL, but no such correlation was found with granulocyte RTL. Our findings challenge conventional expectations, suggesting that shorter mononuclear cell RTL may be associated with favorable functional capacity. The variations in RTL between mononuclear cells and granulocytes highlight their distinct biological roles and turnover rates. A history of immune responses may influence mononuclear cell RTL dynamics, while telomerase activity may protect granulocyte RTL from significant shortening. The unexpected associations observed in mononuclear cell RTL emphasize the complex interplay between immune responses, cellular aging, and functional capacity in older adults.

Hospital admission is associated with disability and late musculoskeletal pain in individuals with long COVID.

Background: The acute clinical repercussions of SARS-CoV-2 infection have been widely studied. However, the possible late repercussions of long COVID have not yet been well defined in the literature. Objectives: To identify the presence of pain and musculoskeletal disability in patients with Long COVID and also to identify predictive factors for pain intensity in this population. Methods: In this cross-sectional and retrospective observational study individuals with Long COVID symptoms were included. It was collected musculoskeletal disability measures, data from patient-related outcome measures and variables from a COVID-19 outpatient service database. Associations and sub-group analyses were performed considering the variables pain, disability and hospitalization. Linear regression was performed to identify predictive factors for pain intensity in Long COVID patients. Results: We evaluated 195 patients and most of them (57%) presented musculoskeletal pain in one area of the body. Pain sub-group presented worse disability indices and worse clinical course during hospitalization. Hospitalized patients presented worse disability indices comparing to non-hospitalized. Significant correlations were found between pain and days of non-invasive oxygen support (r = 0.21; p = 0.003); days in intensive care unit (r = 0.22; p = 0.002) and days in invasive mechanical ventilation (r = 0.35; p = 0.001). Hospitalized individuals showed a higher chance of presenting late musculoskeletal pain (OR = 1.42: 95%CI 1.09-2.04). Days in intensive care unit (ß = 0,234: P = 0,001) and days in invasive mechanical ventilation (ß = 0.764: P = 0.001) were predictors of pain intensity [F(2,192) = 18.559; R2 = 0.231; p = 0.001]. Conclusion: Individuals with Long COVID presented musculoskeletal pain and disability. Hospitalized patients showed a greater chance of having musculoskeletal pain. Days in intensive care unit and days in invasive mechanical ventilation were predictors of late musculoskeletal pain intensity.

Exploring the Fatty Acid Binding Pocket in the SARS-CoV-2 Spike Protein - Confirmed and Potential Ligands.

Severe Acute Respiratory syndrome 2 (SARS-CoV-2) is a respiratory virus responsible for coronavirus disease 19 (COVID-19) and the still ongoing and unprecedented global pandemic. The key viral protein for cell infection is the spike glycoprotein, a surface-exposed fusion protein that both recognizes and mediates entry into host cells. Within the spike glycoprotein, a fatty acid binding pocket (FABP) was confirmed, with the crystallization of linoleic acid (LA) occupying a well-defined site. Importantly, when the pocket is occupied by a fatty acid, an inactive conformation is stabilized, and cell recognition is hindered. In this review, we discuss ligands reported so far for this site, correlating their activity predicted through in silico studies with antispike experimental activity, assessed by either binding assays or cell-infection assays. LA was the first confirmed ligand, cocrystallized in a cryo-EM structure of the spike protein, resulting in increased stability of the inactive conformation of the spike protein. The next identified ligand, lifitegrast, was also experimentally confirmed as a ligand with antiviral activity, suggesting the potential for diverse chemical scaffolds to bind this site. Finally, SPC-14 was also confirmed as a ligand, although no inhibition assays were performed. In this review, we identified 20 studies describing small-molecule compounds predicted to bind the pocket in in silico studies and with confirmed binding or in vitro activity, either inhibitory activity against the spike-ACE2 interaction or antiviral activity in cell-based assays. When considering all ligands confirmed with in vitro assays, a good overall occupation of the pocket should be complemented with the ability to make direct interactions, both hydrophilic and hydrophobic, with key amino acid residues defining the pocket surface. Among the active compounds, long flexible carbon chains are recurrent, with retinoids capable of binding the FABP, although bulkier systems are also capable of affecting viral fitness. Compounds able to bind this site with high affinity have the potential to stabilize the inactive conformation of the SARS-CoV-2 spike protein and therefore reduce the virus's ability to infect new cells. Since this pocket is conserved in highly pathogenic human coronaviruses, including MERS-CoV and SARS-CoV, this effect could be exploited for the development of new antiviral agents, with broad-spectrum anticoronavirus activity.

Minimal-Resource Home Exercise Program Improves Activities of Daily Living, Perceived Health Status, and Shortness of Breath in Individuals with COPD Stages GOLD II to IV.

Home exercises (HE) with minimal resources seem to be useful in individuals with COPD. The objective was to evaluate the effects of HE, on activities of daily living (ADL), dyspnea, on the health status(CAT) and quality of life (HRQoL) of individuals with COPD GOLD II to IV. Quasi-experimental study of the effects of HE, for 2 months, 3 times a week. Individuals with COPD(n = 45) were recruited, 37 started the protocol(9 did not complete it). 28 individuals (mean age 62.04 ± 5.8 years, FEV1: 44.7 ± 2.25%, FEV1/FVC 59.8 ± 6.9%) were evaluated before and after training. We observed improvements in the ADL-Glittre (4.9 ± 1.4 vs 3.9 ± 1.1 min; mean difference: -0.9 ± 0.2 min [95%CI: -1.3 to -0.2]; p = 0.008), as well as the mMRC score(2.8 ± 1.1 vs 2.07 ± 0.81; mean difference: 0.7 ± 0.3 [95%CI: -1.20.18 to -0.2]; p = 0.009), and in the CAT (25.6 ± 4.8 vs 18.9 ± 3.1; mean difference: -6.6 ± 3.4 [95%CI: -10.6 to -1.6]; p = 0.042). Analyzing the mean change before and after the intervention, a weak correlation was observed between ADL-Glittre and mMRC (r = 0.35; [95% CI 0.09; 0.56]; p = 0.009); moderate between ADL-Glittre and CAT (r = 0.52; [95% CI 0.30; 0.69]; p < 0.001) and between ADL-Glittre and SGRQ (r = 0.50; [95% CI 0 .27; 0.67]; p < 0.001). Individuals with COPD can benefit from HE performed autonomously and with minimal resources, as this proposal improves functional capacity for ADL, health perception and dyspnea.

Non-canonical Ca2+- Akt signaling pathway mediates the antiproteolytic effects induced by oxytocin receptor stimulation in skeletal muscle.

Although it has been previously demonstrated that oxytocin (OXT) receptor stimulation can control skeletal muscle mass in vivo, the intracellular mechanisms that mediate this effect are still poorly understood. Thus, rat oxidative skeletal muscles were isolated and incubated with OXT or WAY-267,464, a non-peptide selective OXT receptor (OXTR) agonist, in the presence or absence of atosiban (ATB), an OXTR antagonist, and overall proteolysis was evaluated. The results indicated that both OXT and WAY-267,464 suppressed muscle proteolysis, and this effect was blocked by the addition of ATB. Furthermore, the WAY-induced anti-catabolic action on protein metabolism did not involve the coupling between OXTR and Gαi since it was insensitive to pertussis toxin (PTX). The decrease in overall proteolysis induced by WAY was probably due to the inhibition of the autophagic/lysosomal system, as estimated by the decrease in LC3 (an autophagic/lysosomal marker), and was accompanied by an increase in the content of Ca2+-dependent protein kinase (PKC)-phosphorylated substrates, pSer473-Akt, and pSer256-FoxO1. Most of these effects were blocked by the inhibition of inositol triphosphate receptors (IP3R), which mediate Ca2+ release from the sarcoplasmic reticulum to the cytoplasm, and triciribine, an Akt inhibitor. Taken together, these findings indicate that the stimulation of OXTR directly induces skeletal muscle protein-sparing effects through a Gαq/IP3R/Ca2+-dependent pathway and crosstalk with Akt/FoxO1 signaling, which consequently decreases the expression of genes related to atrophy, such as LC3, as well as muscle proteolysis.

Fasting increases circulating angiotensin levels and brain Agtr1a expression in male rats.

In addition to being recognised for involvement in cardiovascular control and hydromineral balance, the renin-angiotensin system (RAS) has also been associated with the neuroendocrine control of energy balance. One of the main brain sites for angiotensin II (ANG II)/type 1 receptor (AT1 R) signalling is the subfornical organ (SFO), a circumventricular organ related to the control of autonomic functions, motivated behaviours and energy metabolism. Thus, we hypothesised that circulating ANG II may act on the SFO AT1 R receptors to integrate metabolic and hydromineral balance. We evaluated whether food deprivation can modulate systemic RAS activity and Agrt1a brain expression, and if ANG II/AT1 R signalling influences the hypothalamic expression of mRNAs encoding neuropeptides and food and water ingestion in fed and fasted Wistar rats. We found a significant increase in both ANG I and ANG II plasma levels after 24 and 48 h of fasting. Expression of Agrt1a mRNA in the SFO and paraventricular nucleus (PVN) also increased after food deprivation for 48 h. Treatment of fasted rats with low doses of losartan in drinking water attenuated the decrease in glycemia and meal-associated water intake without changing the expression in PVN or arcuate nucleus of mRNAs encoding selected neuropeptides related to energy homeostasis control. These findings point to a possible role of peripheral ANG II/SFO-AT1 R signalling in the control of refeeding-induced thirst. On the other hand, intracerebroventricular losartan treatment decreased food and water intake over dark time in fed but not in fasted rats.

Factors associated with mortality in mechanically ventilated patients with severe acute respiratory syndrome due to COVID-19 evolution.

OBJECTIVES: To evaluate the factors associated with mortality in mechanically ventilated patients with acute respiratory distress syndrome due to COVID-19. METHODS: This was a retrospective, multicenter cohort study that included 425 mechanically ventilated adult patients with COVID-19 admitted to 4 intensive care units. Clinical data comprising the SOFA score, laboratory data and mechanical characteristics of the respiratory system were collected in a standardized way immediately after the start of invasive mechanical ventilation. The risk factors for death were analyzed using Cox regression to estimate the risk ratios and their respective 95%CIs. RESULTS: Body mass index (RR 1.17; 95%CI 1.11 - 1.20; p < 0.001), SOFA score (RR 1.39; 95%CI 1.31 - 1.49; p < 0.001) and driving pressure (RR 1.24; 95%CI 1.21 - 1.29; p < 0.001) were considered independent factors associated with mortality in mechanically ventilated patients with acute respiratory distress syndrome due to COVID-19. Respiratory system compliance (RR 0.92; 95%CI 0.90 - 0.93; p < 0.001) was associated with lower mortality. The comparative analysis of the survival curves indicated that patients with respiratory system compliance (< 30mL/cmH2O), a higher SOFA score (> 5 points) and higher driving pressure (> 14cmH2O) were more significantly associated with the outcome of death at 28 days and 60 days. CONCLUSION: Patients with a body mass index > 32kg/m2, respiratory system compliance < 30mL/cmH2O, driving pressure > 14cmH2O and SOFA score > 5.8 immediately after the initiation of invasive ventilatory support had worse outcomes, and independent risk factors were associated with higher mortality in this population.

Thyroid hormone induces restrictive cardiomyopathy in ß1-adrenoceptor knockout mice.

The purpose of this study was to characterize the role of ß1-AR signaling and its cross-talk between cardiac renin-angiotensin system and thyroid-hormone-induced cardiac hypertrophy. T3 was administered at 0.5 mg·kg-1·day-1 for 10 days in ß1-KOT3 and WTT3 groups, while control groups received vehicle alone. Echocardiography and myocardial histology was performed; cardiac and serum ANGI/ANGII and ANP and cardiac levels of p-PKA, p-ERK1/2, p-p38-MAPK, p-AKT, p-4EBP1, and ACE were measured. WTT3 showed decreased IVSTd and increased LVEDD versus WTsal (p < 0.05). ß1-KOT3 exhibited lower LVEDD and higher relative IVSTd versus ß1-KOsal, the lowest levels of ejection fraction, and the highest levels of cardiomyocyte diameter (p < 0.05). Cardiac ANP levels decreased in WTT3 versus ß1-KOT3 (p < 0.05). Cardiac ACE expression was increased in T3-treated groups (p < 0.05). Phosphorylated-p38 MAPK levels were higher in WTT3 versus WTsal or ß1-KOT3, p-4EBP1 was elevated in ß1-KO animals, and p-ERK1/2 was up-regulated in ß1-KOT3. These findings suggest that ß1-AR signaling is crucial for TiCH.

Estimating cardiopulmonary fitness with a new sampling technology in patients with rheumatoid arthritis-associated interstitial lung disease.

BACKGROUND AND OBJECTIVES: Although peak oxygen uptake (VO2peak ) is one of the most important measures in clinical practice, the high cost and time consumption have led to the search for simpler devices and the development of the estimating cardiopulmonary fitness (eCPF) equation. Since the lungs are one of the sites most affected by rheumatoid arthritis (RA), this study aimed to create a predictive equation for VO2peak obtained by simple sampling technology in women with RA-associated interstitial lung disease (RA-ILD). METHODS: This cross-sectional study evaluated 47 women with RA-ILD. The participants underwent the following evaluations: computed tomography (CT); evaluation of disease activity through the Clinical Disease Activity Index (CDAI); measurement of physical function using the Health Assessment Questionnaire disability index (HAQ-DI); pulmonary function testing, including spirometry, diffusing capacity for carbon monoxide (DlCO ), nitrogen single-breath washout (N2 SBW) test, and impulse oscillometry; and cardiopulmonary exercise testing (CPET) using FitMate™. RESULTS: VO2peak was correlated with age (r = -0.550, p < 0.0001), rheumatoid factor (r = -0.443, p = 0.002), anti-cyclic citrullinated peptide antibodies (r = -0.410, p = 0.004), CDAI (r = -0.462, p = 0.001), HAD-DI (r = -0.486, p = 0.0005), forced vital capacity (r = 0.491, p = 0.0004), DlCO (r = 0.621, p < 0.0001), phase III slope of N2 SBW (r = -0.647, p < 0.0001), resonance frequency (Fres , r = -0.717, p < 0.0001), integrated low-frequency reactance (r = -0.535, p = 0.0001), and the inhomogeneity of respiratory system resistance between 4 and 20 Hz (r = -0.631, p < 0.0001). In the CT examination, patients with extensive ILD had significantly lower VO2peak than patients with limited ILD (p < 0.0001). In the stepwise forward regression analysis, Fres , DlCO and age explained 61% of the VO2peak variability. CONCLUSIONS: As assessed by CPET, women with RA-ILD show reduced cardiopulmonary fitness, which can be explained at least in part by the presence of small airway disease, deterioration of pulmonary gas exchange, and advanced age. These associations of pulmonary variables with eCPF may be clinically important and support the use of the eCPF equation to improve patient outcomes.

Multicomponent oxide microspheres with designed macroporosity (MICROSCAFS®): a customized platform for chemicals immobilization.

A novel versatile, easily recoverable, and recyclable material platform is herein presented, consisting of multicomponent oxide microspheres, of silica-titania and silica-titania-hafnia composition, with tailored interconnected macroporosity (MICROSCAFS®). When functionalized or loaded with desired species, they are potential enablers of emerging applications in environmental remediation, among other fields. We combine emulsion templating for the spherical shape of the particles, with an adapted sol-gel technique involving polymerization-induced phase separation by spinodal decomposition. An advantage of our method regards the employed mix of precursors, which prevents the use of specific gelation additives and porogens and allows a high reproducibility of MICROSCAFS®. We present insight into their formation mechanism using cryo-scanning electron microscopy, and a systematic study of the effect of multiple synthesis parameters on the MICROSCAFS® size and porosity. The composition of the silicon precursors has the most significant effect on fine-tuning the pores size, ranging from the nanometer to the micron scale. Mechanical properties are correlated with morphological features. Larger macroporosity (68% open porosity, estimated by X-ray computed tomography) leads to less stiffness, higher elastic recovery, and compressibility values up to 42%. We believe this study creates a base for consistent custom MICROSCAFS® production, with a design for various future applications.

Learning hybrid locomotion skills-Learn to exploit residual actions and modulate model-based gait control.

This work has developed a hybrid framework that combines machine learning and control approaches for legged robots to achieve new capabilities of balancing against external perturbations. The framework embeds a kernel which is a model-based, full parametric closed-loop and analytical controller as the gait pattern generator. On top of that, a neural network with symmetric partial data augmentation learns to automatically adjust the parameters for the gait kernel, and also generate compensatory actions for all joints, thus significantly augmenting the stability under unexpected perturbations. Seven Neural Network policies with different configurations were optimized to validate the effectiveness and the combined use of the modulation of the kernel parameters and the compensation for the arms and legs using residual actions. The results validated that modulating kernel parameters alongside the residual actions have improved the stability significantly. Furthermore, The performance of the proposed framework was evaluated across a set of challenging simulated scenarios, and demonstrated considerable improvements compared to the baseline in recovering from large external forces (up to 118%). Besides, regarding measurement noise and model inaccuracies, the robustness of the proposed framework has been assessed through simulations, which demonstrated the robustness in the presence of these uncertainties. Furthermore, the trained policies were validated across a set of unseen scenarios and showed the generalization to dynamic walking.

Association of Multiple Cardiovascular Risk Factors with Musculoskeletal Function in Acute Coronary Syndrome Ward Inpatients.

This study explored the association of multiple risk factors with musculoskeletal function in adults hospitalized for acute coronary syndrome. Sixty-nine inpatients (55 ± 6 years; 67% male) admitted to the cardiology ward within <12 h were assessed regarding stress, smoking, alcoholism, hypertension, diabetes mellitus, and obesity. The musculoskeletal function was assessed by predicted values of handgrip strength of the dominant hand (HGS-D%) and maximal inspiratory and expiratory pressures (MIP% and MEP%, respectively). After adjustment by age and sex, drinking habits showed the strongest linear association with the total number of cardiovascular disease risk factors [standardized ß, p-value] (ß = 0.110, p < 0.001), followed by smoking load (ß = 0.028, p = 0.009). Associations were also observed for HGS-D% with mean blood pressure (ß = 0.019 [0.001; 0.037], p = 0.048); MIP% with mean blood pressure (ß = 0.025 [0.006; 0.043], p = 0.013); and MEP% with drinking habits (ß = 0.009 [0.002; 0.016], p = 0.013) and body mass index (ß = 0.008 [0.000; 0.015], p = 0.035). Peripheral and respiratory muscle strength must be interpreted in the context of its association with cardiovascular disease risk factors in adults hospitalized for acute coronary syndrome.

Positive end-expiratory pressure induced changes in airway driving pressure in mechanically ventilated COVID-19 Acute Respiratory Distress Syndrome patients.

BACKGROUND: The profile of changes in airway driving pressure (dPaw) induced by positive-end expiratory pressure (PEEP) might aid for individualized protective ventilation. Our aim was to describe the dPaw versus PEEP curves behavior in ARDS from COVID-19 patients. METHODS: Patients admitted in three hospitals were ventilated with fraction of inspired oxygen (FiO2) and PEEP initially adjusted by oxygenation-based table. Thereafter, PEEP was reduced from 20 until 6 cmH2O while dPaw was stepwise recorded and the lowest PEEP that minimized dPaw (PEEPmin_dPaw) was assessed. Each dPaw vs PEEP curve was classified as J-shaped, inverted-J-shaped, or U-shaped according to the difference between the minimum dPaw and the dPaw at the lowest and highest PEEP. In one hospital, hyperdistention and collapse at each PEEP were assessed by electrical impedance tomography (EIT). RESULTS: 184 patients (41 including EIT) were studied. 126 patients (68%) exhibited a J-shaped dPaw vs PEEP profile (PEEPmin_dPaw of 7.5 ± 1.9 cmH2O). 40 patients (22%) presented a U (PEEPmin_dPaw of 12.2 ± 2.6 cmH2O) and 18 (10%) an inverted-J profile (PEEPmin_dPaw of 14,6 ± 2.3 cmH2O). Patients with inverted-J profiles had significant higher body mass index (BMI) and lower baseline partial pressure of arterial oxygen/FiO2 ratio. PEEPmin_dPaw was associated with lower fractions of both alveolar collapse and hyperinflation. CONCLUSIONS: A PEEP adjustment procedure based on PEEP-induced changes in dPaw is feasible and may aid in individualized PEEP for protective ventilation. The PEEP required to minimize driving pressure was influenced by BMI and was low in the majority of patients.

Water deprivation induces hypoactivity in rats independently of oxytocin receptor signaling at the central amygdala.

Introduction: Vasopressin (AVP) and oxytocin (OXT) are neuropeptides produced by magnocellular neurons (MCNs) of the hypothalamus and secreted through neurohypophysis to defend mammals against dehydration. It was recently demonstrated that MCNs also project to limbic structures, modulating several behavioral responses. Methods and Results: We found that 24 h of water deprivation (WD) or salt loading (SL) did not change exploration or anxiety-like behaviors in the elevated plus maze (EPM) test. However, rats deprived of water for 48 h showed reduced exploration of open field and the closed arms of EPM, indicating hypoactivity during night time. We evaluated mRNA expression of glutamate decarboxylase 1 (Gad1), vesicular glutamate transporter 2 (Slc17a6), AVP (Avpr1a) and OXT (Oxtr) receptors in the lateral habenula (LHb), basolateral (BLA) and central (CeA) amygdala after 48 h of WD or SL. WD, but not SL, increased Oxtr mRNA expression in the CeA. Bilateral pharmacological inhibition of OXTR function in the CeA with the OXTR antagonist L-371,257 was performed to evaluate its possible role in regulating the EPM exploration or water intake induced by WD. The blockade of OXTR in the CeA did not reverse the hypoactivity response in the EPM, nor did it change water intake induced in 48-h water-deprived rats. Discussion: We found that WD modulates exploratory activity in rats, but this response is not mediated by oxytocin receptor signaling to the CeA, despite the upregulated Oxtr mRNA expression in that structure after WD for 48 h.

Factors associated with mortality in mechanically ventilated patients with severe acute respiratory syndrome due to COVID-19 evolution / Fatores associados à mortalidade em pacientes ventilados mecanicamente com síndrome respiratória aguda grave por evolução da COVID-19

ABSTRACT Objectives: To evaluate the factors associated with mortality in mechanically ventilated patients with acute respiratory distress syndrome due to COVID-19. Methods: This was a retrospective, multicenter cohort study that included 425 mechanically ventilated adult patients with COVID-19 admitted to 4 intensive care units. Clinical data comprising the SOFA score, laboratory data and mechanical characteristics of the respiratory system were collected in a standardized way immediately after the start of invasive mechanical ventilation. The risk factors for death were analyzed using Cox regression to estimate the risk ratios and their respective 95%CIs. Results: Body mass index (RR 1.17; 95%CI 1.11 - 1.20; p < 0.001), SOFA score (RR 1.39; 95%CI 1.31 - 1.49; p < 0.001) and driving pressure (RR 1.24; 95%CI 1.21 - 1.29; p < 0.001) were considered independent factors associated with mortality in mechanically ventilated patients with acute respiratory distress syndrome due to COVID-19. Respiratory system compliance (RR 0.92; 95%CI 0.90 - 0.93; p < 0.001) was associated with lower mortality. The comparative analysis of the survival curves indicated that patients with respiratory system compliance (< 30mL/cmH2O), a higher SOFA score (> 5 points) and higher driving pressure (> 14cmH2O) were more significantly associated with the outcome of death at 28 days and 60 days. Conclusion: Patients with a body mass index > 32kg/m2, respiratory system compliance < 30mL/cmH2O, driving pressure > 14cmH2O and SOFA score > 5.8 immediately after the initiation of invasive ventilatory support had worse outcomes, and independent risk factors were associated with higher mortality in this population.

RESUMO Objetivos: Avaliar os fatores associados à mortalidade em pacientes ventilados mecanicamente com síndrome o desconforto respiratório agudo por evolução da COVID-19. Métodos: Estudo de coorte retrospectiva, multicêntrica, que incluiu 425 pacientes adultos com COVID-19, ventilados mecanicamente, internados em 4 unidades de terapia intensiva. Foram coletados dados clínicos que compõem o escore SOFA, dados laboratoriais e características mecânicas do sistema respiratório, de forma padronizada, imediatamente após o início da ventilação mecânica invasiva. Os fatores de risco para óbito foram analisados por meio da regressão de Cox, para estimar as razões de risco, e seus respectivos IC95%. Resultados: Índice de massa corporal (RR de 1,17; IC95% 1,11 - 1,20; p < 0,001), escore SOFA (RR de 1,39; IC95% 1,31 - 1,49; p < 0,001) e driving pressure (RR de 1,24; IC95% 1,21 - 1,29; p < 0,001) foram considerados fatores independentes associados à mortalidade em pacientes ventilados mecanicamente com síndrome do desconforto respiratório agudo por COVID-19. Já a complacência do sistema respiratório (RR de 0,92; IC95% 0,90 - 0,93; p < 0,001) foi associada à menor mortalidade. A análise comparativa das curvas de sobrevida demonstra que pacientes com complacência do sistema respiratório (< 30mL/cmH2O), maior SOFA escore (> 5 pontos) e maior driving pressure (> 14cmH2O) apresentaram maior associação ao desfecho morte em 28 dias e 60 dias. Conclusão: Pacientes com índice de massa corporal > 32kg/m2, complacência do sistema respiratório < 30mL/cmH2O, driving pressure > 14cmH2O e SOFA escore > 5,8, imediatamente após o início da assistência ventilatória invasiva, apresentam piores desfechos no segmento, sendo fatores de risco independentes associados à maior mortalidade nessa população.

Prevalência e caracterização de acidentes domésticos e lazer de idosos em contexto comunitário: Estudo observacional transversal / Prevalence and characterization of home and leisure accidents of Community-dwelling older people: An observational cross-sectional study / Prevalencia y caracterización de los accidentes domésticos y de ocio de las personas mayores en entornos comunitarios: Un estudio observacional transversal

Resumo Enquadramento: O envelhecimento da população contribui para o aumento de acidentes domésticos, com graves consequências pessoais, familiares, sociais. Objetivos: Avaliar a prevalência e caraterísticas de acidentes domésticos em pessoas idosas clientes de unidades funcionais de um Centro de Saúde. Metodologia: Estudo observacional transversal, amostra não probabilística, por conveniência, de 139 pessoas idosas. Resultados: As quedas no domicílio são os acidentes domésticos com maior prevalência nos últimos 12 meses, em sequência de escorregamento. Observaram-se algumas associações baixas, mas estatisticamente significativas, entre o número de quedas, o risco de queda e medo de cair, e entre a idade, o risco de queda e medo de cair. Conclusão: Os resultados observados implicam medidas adequadas por parte dos enfermeiros, integrados em equipas interdisciplinares. A realização de novos estudos de cariz longitudinal, permitirá a monitorização das medidas adotadas e as adaptações necessárias para prevenir e diminuir o risco de queda, e melhorar a qualidade de vida da população envelhecida.

Abstract Background: Population aging contributes to an increase in home accidents, with serious personal, family, and social consequences. Objectives: To assess the prevalence and characteristics of home accidents in older people using functional units of a Health Center. Methodology: Cross-sectional, observational study with a non-probability convenience sample of 139 older people. Results: Falls at home are the most prevalent home accident in the past 12 months, as a consequence of slipping. Some low but statistically significant associations were observed between the number of falls, risk of falling, and fear of falling, and between age, risk of falling, and fear of falling. Conclusion: The results indicate that nurses, integrated into interdisciplinary teams, should take appropriate measures. Further longitudinal studies will allow monitoring the measures adopted and the necessary adaptations to prevent and reduce the risk of falling and improve the quality of life of the aging population.

Resumen Marco contextual: El envejecimiento de la población contribuye a aumentar los accidentes domésticos, con graves consecuencias personales, familiares y sociales. Objetivos: Evaluar la prevalencia y las características de los accidentes domésticos en las personas mayores de las unidades funcionales de un centro de salud. Metodología: Estudio observacional transversal, muestra no probabilística, por conveniencia, de 139 personas mayores. Resultados: Las caídas en el domicilio son los accidentes domésticos más frecuentes en los últimos 12 meses, después de los resbalones. Se observaron algunas asociaciones bajas pero estadísticamente significativas entre el número de caídas, el riesgo de caídas y el miedo a caerse, y entre la edad, el riesgo de caídas y el miedo a caerse. Conclusión: Los resultados observados implican que los enfermeros, integrados en equipos interdisciplinarios, toman las medidas adecuadas. Otros estudios longitudinales permitirán hacer un seguimiento de las medidas adoptadas y de los ajustes necesarios para prevenir y reducir el riesgo de caídas y mejorar la calidad de vida de la población envejecida.