Lymph node colonization induces tumor-immune tolerance to promote distant metastasis.

For many solid malignancies, lymph node (LN) involvement represents a harbinger of distant metastatic disease and, therefore, an important prognostic factor. Beyond its utility as a biomarker, whether and how LN metastasis plays an active role in shaping distant metastasis remains an open question. Here, we develop a syngeneic melanoma mouse model of LN metastasis to investigate how tumors spread to LNs and whether LN colonization influences metastasis to distant tissues. We show that an epigenetically instilled tumor-intrinsic interferon response program confers enhanced LN metastatic potential by enabling the evasion of NK cells and promoting LN colonization. LN metastases resist T cell-mediated cytotoxicity, induce antigen-specific regulatory T cells, and generate tumor-specific immune tolerance that subsequently facilitates distant tumor colonization. These effects extend to human cancers and other murine cancer models, implicating a conserved systemic mechanism by which malignancies spread to distant organs.

Systemic Immunity Is Required for Effective Cancer Immunotherapy.

Immune responses involve coordination across cell types and tissues. However, studies in cancer immunotherapy have focused heavily on local immune responses in the tumor microenvironment. To investigate immune activity more broadly, we performed an organism-wide study in genetically engineered cancer models using mass cytometry. We analyzed immune responses in several tissues after immunotherapy by developing intuitive models for visualizing single-cell data with statistical inference. Immune activation was evident in the tumor and systemically shortly after effective therapy was administered. However, during tumor rejection, only peripheral immune cells sustained their proliferation. This systemic response was coordinated across tissues and required for tumor eradication in several immunotherapy models. An emergent population of peripheral CD4 T cells conferred protection against new tumors and was significantly expanded in patients responding to immunotherapy. These studies demonstrate the critical impact of systemic immune responses that drive tumor rejection.

Exploring the impact of the PNPLA3 I148M variant on primary human hepatic stellate cells using 3D extracellular matrix models.

BACKGROUND & AIMS: The PNPLA3 rs738409 C>G (encoding for I148M) variant is a risk locus for the fibrogenic progression of chronic liver diseases, a process driven by hepatic stellate cells (HSCs). We investigated how the PNPLA3 I148M variant affects HSC biology using transcriptomic data and validated findings in 3D-culture models. METHODS: RNA sequencing was performed on 2D-cultured primary human HSCs and liver biopsies of individuals with obesity, genotyped for the PNPLA3 I148M variant. Data were validated in wild-type (WT) or PNPLA3 I148M variant-carrying HSCs cultured on 3D extracellular matrix (ECM) scaffolds from human healthy and cirrhotic livers, with/without TGFB1 or cytosporone B (Csn-B) treatment. RESULTS: Transcriptomic analyses of liver biopsies and HSCs highlighted shared PNPLA3 I148M-driven dysregulated pathways related to mitochondrial function, antioxidant response, ECM remodelling and TGFB1 signalling. Analogous pathways were dysregulated in WT/PNPLA3-I148M HSCs cultured in 3D liver scaffolds. Mitochondrial dysfunction in PNPLA3-I148M cells was linked to respiratory chain complex IV insufficiency. Antioxidant capacity was lower in PNPLA3-I148M HSCs, while reactive oxygen species secretion was increased in PNPLA3-I148M HSCs and higher in bioengineered cirrhotic vs. healthy scaffolds. TGFB1 signalling followed the same trend. In PNPLA3-I148M cells, expression and activation of the endogenous TGFB1 inhibitor NR4A1 were decreased: treatment with the Csn-B agonist increased total NR4A1 in HSCs cultured in healthy but not in cirrhotic 3D scaffolds. NR4A1 regulation by TGFB1/Csn-B was linked to Akt signalling in PNPLA3-WT HSCs and to Erk signalling in PNPLA3-I148M HSCs. CONCLUSION: HSCs carrying the PNPLA3 I148M variant have impaired mitochondrial function, antioxidant responses, and increased TGFB1 signalling, which dampens antifibrotic NR4A1 activity. These features are exacerbated by cirrhotic ECM, highlighting the dual impact of the PNPLA3 I148M variant and the fibrotic microenvironment in progressive chronic liver diseases. IMPACT AND IMPLICATIONS: Hepatic stellate cells (HSCs) play a key role in the fibrogenic process associated with chronic liver disease. The PNPLA3 genetic mutation has been linked with increased risk of fibrogenesis, but its role in HSCs requires further investigation. Here, by using comparative transcriptomics and a novel 3D in vitro model, we demonstrate the impact of the PNPLA3 genetic mutation on primary human HSCs' behaviour, and we show that it affects the cell's mitochondrial function and antioxidant response, as well as the antifibrotic gene NR4A1. Our publicly available transcriptomic data, 3D platform and our findings on NR4A1 could facilitate the discovery of targets to develop more effective treatments for chronic liver diseases.

Acquisition of elemental sulfur by sulfur-oxidising Sulfolobales.

Elemental sulfur (S8 0)-oxidising Sulfolobales (Archaea) dominate high-temperature acidic hot springs (>80°C, pH <4). However, genomic analyses of S8 0-oxidising members of the Sulfolobales reveal a patchy distribution of genes encoding sulfur oxygenase reductase (SOR), an S8 0 disproportionating enzyme attributed to S8 0 oxidation. Here, we report the S8 0-dependent growth of two Sulfolobales strains previously isolated from acidic hot springs in Yellowstone National Park, one of which associated with bulk S8 0 during growth and one that did not. The genomes of each strain encoded different sulfur metabolism enzymes, with only one encoding SOR. Dialysis membrane experiments showed that direct contact is not required for S8 0 oxidation in the SOR-encoding strain. This is attributed to the generation of hydrogen sulfide (H2S) from S8 0 disproportionation that can diffuse out of the cell to solubilise bulk S8 0 to form soluble polysulfides (Sx 2-) and/or S8 0 nanoparticles that readily diffuse across dialysis membranes. The Sulfolobales strain lacking SOR required direct contact to oxidise S8 0, which could be overcome by the addition of H2S. High concentrations of S8 0 inhibited the growth of both strains. These results implicate alternative strategies to acquire and metabolise sulfur in Sulfolobales and have implications for their distribution and ecology in their hot spring habitats.

Effect of Preoperative Home-Based Exercise Training on Quality of Life After Lung Cancer Surgery: A Multicenter Randomized Controlled Trial.

BACKGROUND: Preoperative exercise training is recommended for improvement of clinical outcomes after lung cancer (LC) surgery. However, its effectiveness in preventing postoperative decline in quality of life (QoL) remains unknown. This study investigated the effect of preoperative home-based exercise training (PHET) on QoL after LC surgery. METHODS: Patients awaiting LC resection were randomized to PHET or a control group (CG). The PHET program combined aerobic and resistance exercise, with weekly telephone supervision. Primary outcome was QoL-assessed with the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 (QLQ-C30) at baseline, before surgery, and 1 month after surgery. The secondary outcomes were hospital length of stay and physical performance. The main analysis included a factorial repeated-measures analysis of variance. Additionally, the proportion of patients experiencing clinical deterioration from baseline to post-surgery was assessed. RESULTS: The study included 41 patients (68.1 ± 9.3 years; 68.3% male) in the intention-to-treat analysis (20 PHET patients, 21 CG patients). A significant group × time interaction was observed for global QoL (p = 0.004). Between-group differences in global QoL were statistically and clinically significant before surgery (mean difference [MD], 13.5 points; 95% confidence interval [CI], 2.4-24.6; p = 0.019) and after surgery (MD, 12.4 points; 95% CI, 1.3-23.4; p = 0.029), favoring PHET. Clinical deterioration of global QoL was reported by 71.4% of the CG patients compared with 30 % of the PHET patients (p = 0.003). Between-group differences in favor of PHET were found in pain and appetite loss as well as in physical, emotional and role functions after surgery (p < 0.05). Compared with CG, PHET was superior in improving preoperative five-times sit-to-stand and postoperative exercise capacity (p < 0.05). No between-group differences in other secondary outcomes were observed. CONCLUSION: The study showed that PHET can effectively prevent the decline in QoL after LC surgery.

Alpha 1-acid glycoprotein is upregulated in severe COVID-19 patients and decreases neutrophil NETs in SARS-CoV-2 infection.

Orosomucoid, or alpha-1 acid glycoprotein (AGP), is a major acute-phase protein expressed in response to systemic injury and inflammation. AGP has been described as an inhibitor of neutrophil migration on sepsis, particularly its immunomodulation effects. AGP's biological functions in coronavirus disease 2019 (COVID-19) are not understood. We sought to investigate the role of AGP in severe COVID-19 infection patients and neutrophils infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Epidemiological data, AGP levels, and other laboratory parameters were measured in blood samples from 56 subjects hospitalized in the ICU with SARS-CoV-2 infection. To evaluate the role of AGP in NETosis in neutrophils, blood samples from health patients were collected, and neutrophils were separated and infected with SARS-CoV-2. Those neutrophils were treated with AGP or vehicle, and NETosis was analyzed by flow cytometry. AGP was upregulated in severe COVID-19 patients (p<0.05). AGP level was positively correlated with IL-6 and C-reactive protein (respectively, p=0.005, p=0.002) and negatively correlated with lactate (p=0.004). AGP treatment downregulated early and late NETosis (respectively, 35.7% and 43.5%) in neutrophils infected with SARS-CoV-2 and up-regulated IL-6 supernatant culture expression (p<0.0001). Our data showed increased AGP in COVID-19 infection and contributed to NETosis regulation and increased IL-6 production, possibly related to the Cytokine storm in COVID-19.

Neutral and Anion Species of Quinoidal Thienothiophene Diketopyrrolopyrroles Display a Common Aggregation Mode.

A comprehensive investigation of two new molecular triads incorporating the diketopyrrolopyrrole unit into a quinoidized thienothiophene skeleton, which is further end-capped with dicyanomethylene (DPP-TT-CN) or phenoxyl groups (DPP-TT-PhO), has been carried out. A combination of UV-Vis-NIR and infrared spectroelectrochemical techniques and cryogenic UV-Vis-NIR absorption spectroscopy supported by theoretical calculations has been used. The main result is the formation of similar H-aggregates in the dimerization process of the neutral molecules and of the charged anionic species. The experimental absorption spectra of the aggregated species are accurately reproduced by quantum chemical calculations using the Spano's model, including excitonic coupling for the dimeric forms and full vibronic resolution of the absorption bands. The strong excitonic coupling taking place is key to understand the electronic structure of the dimeric aggregates and has been instrumental to disentangle the type of H-aggregation. This study is of relevance to get a better understanding of the molecular aggregation of organic p-conjugated chromophores and is useful as a guideline for the refinement of the engineering of molecular materials for which supramolecular design is required.

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

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

Curved Nanographenes as Stoppers in a [2]Rotaxane with Two-Photon Excited Emission.

Heptagon-containing distorted nanographenes are used as stoppers for the capping of a [2]rotaxane through a Michael-type addition reaction to vinyl sulfone groups. These curved aromatics are bulky enough to prevent the disassembly of the rotaxane but also give emissive and nonlinear (two-photon absorption and emission) optical properties to the structure.

Morphology of nares associated with stereo-olfaction in baleen whales.

The sensory mechanisms used by baleen whales (Mysticeti) for locating ephemeral, dense prey patches in vast marine habitats are poorly understood. Baleen whales have a functional olfactory system with paired rather than single blowholes (nares), potentially enabling stereo-olfaction. Dimethyl sulfide (DMS) is an odorous gas emitted by phytoplankton in response to grazing by zooplankton. Some seabirds use DMS to locate prey, but this ability has not been demonstrated in whales. For 14 extant species of baleen whale, nares morphometrics (imagery from unoccupied aerial systems, UAS) was related to published trophic level indices using Bayesian phylogenetic mixed modelling. A significant negative relationship was found between nares width and whale trophic level (ß = -0.08, lower 95% CI = -0.13, upper 95% CI = -0.03), corresponding with a 39% increase in nares width from highest to lowest trophic level. Thus, species with nasal morphology best suited to stereo-olfaction are more zooplanktivorous. These findings provide evidence that some baleen whale species may be able to localize odorants e.g. DMS. Our results help direct future behavioural trials of olfaction in baleen whales, by highlighting the most appropriate species to study. This is a research priority, given the potential for DMS-mediated plastic ingestion by whales.

Unravelling the role of proline in glyphosate-mediated toxicity - tolerance mechanism or stress signal?

Glyphosate (GLY), the most widely used herbicide, has been regarded as an emergent environmental contaminant due to its constant and cumulative use, with potential harm to non-target organisms, such as crops, disrupting cells' redox balance. Therefore, plants need to fine-tune their antioxidant (AOX) mechanisms to thrive under GLY-contaminated environments. Proline overaccumulation is a common response in plants exposed to GLY, yet its role in GLY-induced toxicity remains unclear. Thus, this study explores whether Pro overaccumulation in response to GLY is perceived as a downstream tolerance mechanism or an early-warning stress signal. To investigate this, Arabidopsis thaliana T-DNA mutant lines for Pro biosynthetic (P5CS1) and catabolic genes (ProDH) were used and screened for their GLY susceptibility. Upon seedlings' exposure to GLY (0.75 mg L-1) for 14 days, the herbicide led to reduced biomass in all genotypes, accompanied by Pro overaccumulation. Mutants with heightened Pro levels (prodh) exhibited the greatest biomass reduction, increased lipid peroxidation (LP), and hydrogen peroxide (H2O2) levels, accompanied by a compromised performance of the AOX system. Conversely, p5cs1-4, mutants with lower Pro levels, demonstrated an enhanced AOX system activation, not only with increased levels of glutathione (GSH) and ascorbate (AsA), but also with increased activity of both ascorbate peroxidase (APX) and catalase (CAT). These findings suggest that Pro overaccumulation under GLY exposure is associated with stress sensitivity rather than tolerance, highlighting its potential as an early-warning signal for GLY toxicity in non-target plants and for detecting weed resistance.

High male sexual investment as a driver of extinction in fossil ostracods.

Sexual selection favours traits that confer advantages in the competition for mates. In many cases, such traits are costly to produce and maintain, because the costs help to enforce the honesty of these signals and cues 1 . Some evolutionary models predict that sexual selection also produces costs at the population level, which could limit the ability of populations to adapt to changing conditions and thus increase the risk of extinction2-4. Other models, however, suggest that sexual selection should increase rates of adaptation and enhance the removal of deleterious mutations, thus protecting populations against extinction3, 5, 6. Resolving the conflict between these models is not only important for explaining the history of biodiversity, but also relevant to understanding the mechanisms of the current biodiversity crisis. Previous attempts to test the conflicting predictions produced by these models have been limited to extant species and have thus relied on indirect proxies for species extinction. Here we use the informative fossil record of cytheroid ostracods-small, bivalved crustaceans with sexually dimorphic carapaces-to test how sexual selection relates to actual species extinction. We show that species with more pronounced sexual dimorphism, indicating the highest levels of male investment in reproduction, had estimated extinction rates that were ten times higher than those of the species with the lowest investment. These results indicate that sexual selection can be a substantial risk factor for extinction.

Lower limit of normal of cross-sectional area of peripheral muscles and diaphragm measurements performed with ultrasound in full-term and preterm infants.

To stratify groups of infants by gestational age and identify the lower limit of normal (LLN) of the cross-sectional area of peripheral muscles as well as diaphragmatic excursion and thickness and parasternal activation during spontaneous respiration in full-term and preterm newborns. A cross-sectional study was conducted at a neonatal unit. Preterm newborns (PTNBs) with gestational age of 28 to 366/7 weeks and full-term newborns (NBs) with gestational age of 37 to 416/7 weeks, clinically and hemodynamically stable, breathing ambient air with no signs of respiratory distress were included. NBs on oxygen therapy, those with known genetic syndromes, malformations of the nervous system and those having undergone surgery were excluded. Ultrasound was performed over the rectus femoris, tibialis anterior, and biceps brachii muscles (cross-sectional area) and diaphragm (thickness and excursion). One hundred twenty NBs were stratified based on gestational age (< 30 weeks [n = 25]; 31 to 35 weeks [n = 51]; 37 to 41 6/7 weeks [n = 44]). Significant differences were found in the cross-sectional area of the rectus femoris muscles and thigh circumference of NBs > 37 weeks compared to the other 2 groups (p < 0.05). Differences were found in diaphragm thickness and excursion between the groups with gestational age > 37 weeks and < 30 weeks. Greater activation of the parasternal muscles was found in the PTNBs. With regard to LLN, significant differences were found between the groups with gestational age > 37 weeks and < 30 weeks for all variables analyzed and between the group with gestational age > 37 weeks and other 2 groups for the cross-sectional area of the rectus femoris, diaphragmatic excursion, and diaphragm contraction velocity. Differences were found among the groups in the size of peripheral muscles as well as diaphragm thickness and excursion. Moreover, greater activation of the parasternal muscle was found in NBs with gestational age < 30 weeks. This study establishes normal values of ultrasound measures for full-term and preterm newborns.

Determinants of pregnant women's satisfaction with interactions with health providers at antenatal consultation in primary health care in Southern Mozambique in 2021: a cross-sectional study.

BACKGROUND: The Ministry of Health of Mozambique (MISAU) and the World Health Organization (WHO) recommend enhancing pregnant women's satisfaction with health care services in order to advance maternal and child health. This study aims to assess the levels and determinants of pregnant women's satisfaction regarding their interactions with antenatal care (ANC) providers, the services of which were provided at the primary health care level in southern Mozambique. METHODOLOGY: We conducted an observational, quantitative, and cross-sectional study from November 4 to December 10, 2021. A structured questionnaire was administered to pregnant women who attended ANC during that period. The characteristics of the participants were illustrated using descriptive statistics; to analyse pregnant women's satisfaction determinants, we estimated crude and adjusted odds ratios (AOR) and 95% confidence intervals (95% CI) using logistic regression models. All analyses were performed in SPSS version 24 using a 5% significance level. RESULTS: We selected 951 pregnant women with a mean age of 25 years old; 14% attained a secondary educational level, 36% were married or living in a marital relationship, and 85.9% reported being satisfied with their current ANC. Factors that reduced the odds of being satisfied were the following: an "insufficient" ANC duration (AOR = 0.173; 95% CI: 0.079, 0.381); inadequate ANC waiting area (AOR = 0.479; 95% CI: 0.265, 0.863); women's perception about the existing norm of nonattendance in case of late arrival to the ANC (AOR = 0.528; 95% CI 0.292, 0.954); the perception of the existing norm that women are obliged to give birth in same health facility where ANC occurred (AOR = 0.481; 95% CI: 0.273, 0.846); and the perception that delivered ANC is not important for foetal health (AOR = 0.030; 95% CI:0.014, 0.066). CONCLUSIONS: Most of the pregnant women mentioned being satisfied with the ANC they received. The perception of short consultation duration, inadequate waiting spaces, strict linkage rules to specific health facilities and ANC norms, the perception that the received ANC is not relevant for foetal well-being are determinants of not being satisfied with ANC, and these determinants can be addressed by reorganizing ANC and, indeed, are modifiable by the improved paced implementation of the MISAU strategies for quality maternal and child health care.

Cytomegalovirus congenital infection: long-term outcomes in a valaciclovir treated population.

OBJECTIVES: This case series aims to evaluate the long-term outcomes of congenital cytomegalovirus (CMV) infection in a population treated with valaciclovir during pregnancy. The study focuses on assessing the prevalence of long-term sequelae in infants with confirmed CMV fetal infection. METHODS: A retrospective analysis was conducted on 33 pregnancies corresponding to 34 fetus with confirmed CMV congenital infection. They were followed from November 2004 to December 2020. Valaciclovir treatment was initiated after confirmation of fetal infection, and fetal outcomes were monitored through serial ultrasounds, neurosonography, and fetal magnetic resonance imaging (MRI). Postnatal assessments included: PCR confirmation, symptoms evaluation at birth, and long-term follow-up protocols for visual, auditory, and neurodevelopmental assessment. RESULTS: Therapy was started at a median gestational age of 24 weeks. Of the 34 newborns 79.4 % were asymptomatic at birth. Median follow-up time was 6 years and 32.35 % developed long-term sequelae. Neurosensorial hearing loss (SNHL) was the predominant sequelae. In the cases which developed sequelae 54.5 % had imaging findings, and all with major findings developed long-term sequelae. CONCLUSIONS: In our treated population we had a higher asymptomatic rate at birth comparing with a non-treated population, similar to those found in previous studies. We had a long-term sequelae rate of 32.35 %, similar to recent studies on non-treated population, although we registered a slightly lower rate of SNHL. A larger multicenter studies with a longer follow-up time, where treatment is started in the first trimester, is of the utmost importance, so we can truly understand the correlation between these imaging findings, therapy and long-term sequelae.

Antifungal, molecular docking and cytotoxic effect of the essential oil of Cymbopogon citratus (DC) Stapf. and Cymbopogon nardus (L.) Rendle against Candida albicans.

Brazil is renowned for its extensive plant biodiversity, with emphasis on Cymbopogon, C. citratus and C. nardus, with broad antimicrobial potential. Candidemias caused by Candida albicans are highly prevalent in immunosuppressed individuals and are associated with infections by biofilms on medical devices. The aim of this study was to evaluate the antimicrobial potential of essential oils C. citratus and C. nardus against C. albicans in planktonic and biofilm forms. Essential oils were obtained by hydrodistillation and chemical composition evaluated by GC-FID and GC-MS. The minimum inhibitory concentration was determined by the broth microdilution method and the synergy effect of essential oils and amphotericin B were evaluated by the checkerboard test. Biofilm activity was determined by the XTT assay. Cytotoxicity assays performed with VERO cells and molecular docking were performed to predict the effect of oil interaction on the SAP-5 enzyme site. The results showed activity of essential oils against planktonic cells and biofilm of C. albicans. Furthermore, the oils had a synergistic effect, and low cytotoxicity. Molecular docking showed interaction between Cadinene, Caryophyllen oxide, Germacrene D with SAP-5. The results indicate that Cymbopogon spp. studied are anti-Candida, with potential for further application in therapy against infections caused by C. albicans.

Insights into alternative cryoprotectants to freeze sperm of domestic cats.

Globalization and habitat destruction pose a significant threat to wildlife felids. Even though conservation banks for genetic materials have been created, the sperm cryopreservation with minimal cell damage is still a great challenge. Thus, this study aimed to compare the effects of two commercial extenders with different concentrations of alternative cryoprotectants on thawed sperm quality of domestic cats. Five adult cats were anaesthetized (using a combination of 40 µg/kg medetomidine associated to 5 mg/kg ketamine), and the semen was collected by electroejaculation (electrical stimulation of 2-3 V). Semen samples were evaluated for sperm characteristics (kinetics, morphology, membrane integrity and morphometry). Subsequently, they were sorted into two aliquots and centrifuged. The aliquots were added to a commercial extender containing 3% glycerol and 2% methylformamide (extender I) or 2% glycerol and 3% methylformamide (extender II), frozen, thawed (37°C/30 s) and reevaluated. Comparatively, the sperm kinetics and membrane integrity of fresh semen were higher (p < .002) than frozen samples in extender I and II. Total and progressive motility were lowest in the thawed samples. However, the subjective analysis indicated high sperm motility, since the kinetics evaluation was impaired by the low cell number in the thawed samples. There were no differences in sperm morphology between the groups. In the sperm morphometric analysis, a significant difference (p = .04) was identified in the length of the intermediate piece in extender II samples compared with fresh and extender I. Thus, it can be concluded that although the concentrations tested did not maintain the kinetic parameters and membrane integrity of spermatozoa after thawing, the extender with a lower concentration of glycerol was less toxic for maintaining the midpiece length.

Renal biomarkers, clinical parameters, and renal Doppler velocimetry in bitches with cystic endometrial hyperplasia-pyometra complex.

Cystic endometrial hyperplasia (CEH)-pyometra complex is the most common uterine infection in adult and elderly bitches and can cause renal dysfunction. The aim of this study was to measure and compare urinary creatinine, urea, symmetric dimethylarginine (SDMA), urinary protein-creatinine ratio (UPC), measurement of systolic blood pressure (SBP), and Doppler velocimetry of renal arteries in patients with CEH-pyometra complex before and after an average of 6 months of treatment, evaluating the possibility of the changes persisting. The evaluation was conducted at two moments: M1 (at the diagnosis of CEH-pyometra, n = 36) and M2 (after an average of six months of treatment, n = 16). For the control group, eight bitches with no changes in blood tests or history of conditions underwent Doppler ultrasound evaluation of the renal arteries. At both M1 and M2, we measured creatinine, urea, and serum SDMA, UPC, SBP, and Doppler ultrasound of the renal arteries. Patients were evaluated according to the following groups: azotemic (AZO) and non-azotemic (NAZO), and open and closed cervix pyometra. The parameters were compared between animals present in both moments presented as M1R (bitches that were in M1 and M2) and M2. Statistical significance was considered when p < .05. The medians found for creatinine in M1 were as follows: 1.15 mg/dL, being 1.8 mg/dL for AZO (12/36) and 0.95 mg/dL for NAZO (24/36); and in M2: 0.85 mg/dL (16/16), being 1.15 mg/dL for AZO (4/16) and 0.8 mg/dL for NAZO (12/36). For urea, in M1 it was 36 mg/dL (32/36), with AZO being 103 mg/dL (11/32) and 33 mg/dL in NAZO (21/32); and in M2 32 mg/dL (16/ 16), being 29 mg/dL for AZO (4/36), and 31 mg/dL for NAZO (3/15). The median SDMA measured in M1R was 17 µg/dL (15/16), with AZO being 31 µg/dL (3/15), and NAZO being 16.5 µg/dL (12/15); and in M2, SDMA was 12 µg/dL (16/16), with AZO being 12.5 µg/dL (4/16), and NAZO being 12 µg/dL (12/16). The median UPC measured in M1 was 1.15 (10/36), with AZO being 0.25 (1/10), and NAZO being 1.38 (9/10); and in M2, it was 0.2 (13/16), being 0.1 in AZO (4/13), and 0.2 (9/16) in NAZO. For SBP, in M1, it was 118 mmHg (30/36), with AZO being 102 mmHg (10/30) and 133 mmHg in NAZO (20/30); and in M2 142.5 mmHg (12/16), being 155 mmHg for AZO (4/12), and 140 mg/dL for NAZO (8/12). When comparing animals with open and closed cervixes, a difference was found between SDMA measurements (p = .001). There was a distinction between PI and RI of the left and right kidneys consecutively (p = .007; p = .033; p = .019; p = .041). Correlations found in M1: SDMA × PI RIM DIR (r = 0.873; p = .002), SDMA × PSV RIM ESQ (r = 0.840; p = .004), SDMA × EDV RIM ESQ (r = 0.675; p = .046). With this study, we conclude a return to normality of renal biomarkers and clinical parameters after six months. Yet, there is a persistence of Doppler velocimetric measurements between the two moments. Thus, this parameter is not suitable for identifying and classifying chronic kidney injury in bitches with pyometra.

Effects of two external cooling strategies on physiological and perceptual responses of athletes with tetraplegia during and after exercise in the heat.

Athletes with tetraplegia may experience marked hyperthermia while exercising under environmental heat stress due to their limited ability to dissipate heat through evaporative means. This study investigated the effectiveness of two external cooling strategies (i.e., spraying water onto the body surface or using a cooling vest) on physiological and perceptual variables in tetraplegic athletes during and after an aerobic exercise session in a hot environment. Nine male wheelchair rugby players performed an incremental test to determine their maximum aerobic power output. After that, they were subjected to three experimental trials in a counter-balanced order: control (CON, no body cooling), cooling vest (CV), and water spraying (WS). During these trials, they performed 30 min of a submaximal exercise (at 65% of their maximum aerobic power) inside an environmental chamber set to maintain the dry-bulb temperature at 32 °C. The following variables were recorded at regular intervals during the exercise and for an additional 30 min following the exertion (i.e., post-exercise recovery) with the participants also exposed to 32 °C: body core temperature (TCORE), skin temperature (TSKIN), heart rate (HR), rating of perceived exertion (RPE), thermal comfort (TC), and thermal sensation (TS). While exercising in CON conditions, the tetraplegic athletes had the expected increases in TCORE, TSKIN, HR, RPE, and TC and TS scores. HR, TC, and TS decreased gradually toward pre-exercise values after the exercise, whereas TCORE and TSKIN remained stable at higher values. Using a cooling vest decreased the temperature measured only on the chest and reduced the scores of RPE, TC, and TS during and after exercise but did not influence the other physiological responses of the tetraplegic athletes. In contrast, spraying water onto the athletes' body surface attenuated the exercise-induced increase in TSKIN, led to lower HR values during recovery, and was also associated with better perception during and after exercise. We conclude that water spraying is more effective than the cooling vest in attenuating physiological strain induced by exercise-heat stress. However, although both external cooling strategies do not influence exercise hyperthermia, they improve the athletes' thermal perception and reduce perceived exertion.

Beach wrack: Discussing ecological roles, risks, and sustainable bioenergy and agricultural applications.

The equilibrium of the marine ecosystem is currently threatened by several constraints, among which climate change and anthropogenic activities stand out. Indeed, these factors favour the growth of macroalgae, which sometimes end up stranded on the beaches at the end of their life cycle, forming what is known as beach wrack. Despite its undeniable important ecological role on beaches, as it is an important source of organic matter (OM), and provides food and habitat for several invertebrates, reptiles, small mammals, and shorebirds, the overaccumulation of beach wrack is often associated with the release of greenhouse gases, negatively impacting tourist activities, and generating economic expenses for its removal. Although currently beach wrack is mainly treated as a waste, it can be used for numerous potential applications in distinct areas. This review aimed at providing a solid point of view regarding the process of wrack formation, its spatiotemporal location, as well as its importance and risks. It also contains the current advances of the research regarding sustainable alternatives to valorise this organic biomass, that range from bioenergy production to the incorporation of wrack in agricultural soils, considering a circular economy concept. Although there are some concerns regarding wrack utilisation, from its variable availability to a possible soil contamination with salts and other contaminants, this review comprises the overall beneficial effects of the incorporation of this residue particularly in the organic agricultural model, strengthening the conversion of this wasted biomass into a valuable resource.