Periparturient blood T-lymphocyte PD-1 and CTLA-4 expression as potential predictors of new intramammary infections in dairy cows during early lactation (short communication).

BACKGROUND: The periparturient period in dairy cows is marked by immunosuppression which increases the likelihood of infectious disorders, particularly also mastitis. An in-depth understanding of peripartum leukocyte biology is vital for the implementation of highly successful post-partum disease prevention measures. Immune checkpoint molecules, such as programmed death 1 (PD-1) and cytotoxic T-lymphocyte antigen 4 (CTLA-4), are critical inhibitory receptors expressed on immune cells, particularly T cells, that drive immunosuppressive signaling pathways. However, the potential role of immune checkpoint molecules expression in T-cells on udder health has never been explored. Thus, the association between the occurrence of new postpartum intramammary infections (IMIs) and the expression of programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) on blood T-cells during the peripartum period was investigated. RESULTS: In this study, the incidence of IMIs by any pathogen in early lactation was not associated with a higher expression of PD-1 and CTLA-4 in the periparturient period. However, the incidence of IMIs by major pathogens throughout the first month of lactation was significantly associated with higher expression of PD-1 at 14 days before calving (P = 0.03) and CTLA-4 at parturition (P = 0.03) by blood T-cells. Also, the expression of CTLA-4 at D0 (P = 0.012) by T-cells was associated with the occurrence of persistent IMIs during the first month of lactation. CONCLUSIONS: To our knowledge, this is the first report to investigate the expression of PD-1 and CTLA-4 by blood T-lymphocytes during the periparturient period in dairy cows and to explore their relationship with the incidence of new IMIs in the postpartum period. Thus, a comprehensive understanding of leukocyte biology during peripartum would appear to be a prerequisite for the identification of resilient dairy cows or targets innovative (immunological) non-antibiotic approaches in the transition period.

The metabolic interplay between dietary carbohydrate and exercise and its role in acute appetite regulation in males: a randomized controlled study.

An understanding of the metabolic determinants of postexercise appetite regulation would facilitate development of adjunctive therapeutics to suppress compensatory eating behaviours and improve the efficacy of exercise as a weight-loss treatment. Metabolic responses to acute exercise are, however, dependent on pre-exercise nutritional practices, including carbohydrate intake. We therefore aimed to determine the interactive effects of dietary carbohydrate and exercise on plasma hormonal and metabolite responses and explore mediators of exercise-induced changes in appetite regulation across nutritional states. In this randomized crossover study, participants completed four 120 min visits: (i) control (water) followed by rest; (ii) control followed by exercise (30 min at ∼75% of maximal oxygen uptake); (iii) carbohydrate (75 g maltodextrin) followed by rest; and (iv) carbohydrate followed by exercise. An ad libitum meal was provided at the end of each 120 min visit, with blood sample collection and appetite assessment performed at predefined intervals. We found that dietary carbohydrate and exercise exerted independent effects on the hormones glucagon-like peptide 1 (carbohydrate, 16.8 pmol/L; exercise, 7.4 pmol/L), ghrelin (carbohydrate, -48.8 pmol/L; exercise: -22.7 pmol/L) and glucagon (carbohydrate, 9.8 ng/L; exercise, 8.2 ng/L) that were linked to the generation of distinct plasma 1 H nuclear magnetic resonance metabolic phenotypes. These metabolic responses were associated with changes in appetite and energy intake, and plasma acetate and succinate were subsequently identified as potential novel mediators of exercise-induced appetite and energy intake responses. In summary, dietary carbohydrate and exercise independently influence gastrointestinal hormones associated with appetite regulation. Future work is warranted to probe the mechanistic importance of plasma acetate and succinate in postexercise appetite regulation. KEY POINTS: Carbohydrate and exercise independently influence key appetite-regulating hormones. Temporal changes in postexercise appetite are linked to acetate, lactate and peptide YY. Postexercise energy intake is associated with glucagon-like peptide 1 and succinate levels.

Understanding plant responses to saline waterlogging: insights from halophytes and implications for crop tolerance.

MAIN CONCLUSION: Saline and wet environments stress most plants, reducing growth and yield. Halophytes adapt with ion regulation, energy maintenance, and antioxidants. Understanding these mechanisms aids in breeding resilient crops for climate change. Waterlogging and salinity are two abiotic stresses that have a major negative impact on crop growth and yield. These conditions cause osmotic, ionic, and oxidative stress, as well as energy deprivation, thus impairing plant growth and development. Although few crop species can tolerate the combination of salinity and waterlogging, halophytes are plant species that exhibit high tolerance to these conditions due to their morphological, anatomical, and metabolic adaptations. In this review, we discuss the main mechanisms employed by plants exposed to saline waterlogging, intending to understand the mechanistic basis of their ion homeostasis. We summarize the knowledge of transporters and channels involved in ion accumulation and exclusion, and how they are modulated to prevent cytosolic toxicity. In addition, we discuss how reactive oxygen species production and cell signaling enhance ion transport and aerenchyma formation, and how plants exposed to saline waterlogging can control oxidative stress. We also address the morphological and anatomical modifications that plants undergo in response to combined stress, including aerenchyma formation, root porosity, and other traits that help to mitigate stress. Furthermore, we discuss the peculiarities of halophyte plants and their features that can be leveraged to improve crop yields in areas prone to saline waterlogging. This review provides valuable insights into the mechanisms of plant adaptation to saline waterlogging thus paving the path for future research on crop breeding and management strategies.

Metabolites of non-aureus staphylococci affect the ability of Staphylococcus aureus to adhere to and internalize into bovine mammary epithelial cells.

This study investigated whether cell-free supernatants (SN) from four bovine non-aureus staphylococcal (NAS) isolates prevent Staphylococcus aureus adhesion to and internalization into bovine mammary epithelial cells (MAC-T cells) and if so, to determine whether such effects were potentially associated with the S. aureus accessory gene regulator (agr) system. Overall, we demonstrated that all SN obtained from the NAS isolates promoted adhesion of a S. aureus agr+ strain to, yet reduced the internalization into MAC-T cells, while similar effects were not observed for its agr- mutant strain. Our findings provide novel anti-virulence strategies for treating and controlling bovine S. aureus mastitis.

[Housing support after long-term psychiatric hospitalization: Resources and strategies in three experiences in Buenos Aires Province, Argentina]. / Los apoyos a la vivienda tras internaciones psiquiátricas prolongadas: recursos y estrategias en tres experiencias de la Provincia de Buenos Aires, Argentina.

INTRODUCTION: Housing is one of the main supports needed to guarantee community life of people who had long-term psychiatric hospitalizations. In Argentina, housing support experiences have been developed for decades, although their systematization is scarce. The objective of this paper is to describe three housing support experiences developed in the province of Buenos Aires, Argentina, which have continuity over time for more than 20 years. MATERIALS AND METHODS: Document analysis and interviews with workers from the three experiences were carried out, as part of a broader project on community life and neighborhood relations of people discharged after long-term psychiatric hospitalizations. The material was analyzed qualitatively, using a time dimension and a structure and functioning one which included financing, technical resources, housing devices and support provided. RESULTS: Although the types of support provided are somehow similar between the three experiences, heterogeneity in structure and functioning is observed. DISCUSSION AND CONCLUSIONS: Despite the fact that the human rights framework proposes the provision of flexible and adequate support according to the needs of people, it is worth reflection on whether the reduced systematization of experiences such as those presented is due to the difficulties of the heterogeneity mentioned, or is due to a scarce evaluation culture that obstacles the learning from those experiences.

Incidence of venous thromboembolism among patients with severe COVID-19 requiring mechanical ventilation compared to other causes of respiratory failure: a prospective cohort study.

Previous studies have suggested that COVID-19 pneumonia is associated with an increased risk of venous thromboembolism (VTE). This study aimed to investigate the incidence of VTE among mechanically ventilated adults with COVID-19 pneumonia, compared to patients with respiratory failure related to other causes. Prospective study that enrolled critically ill adults with suspected COVID-19 pneumonia between June 2, 2020 and August 11, 2020. Critically ill adults with suspected COVID-19 pneumonia who required mechanical ventilation within 24 h after hospital admission were followed until death or hospital discharge. Sequential ultrasonography screening of the lower extremities and catheter insertion sites, as well as testing for plasma biochemical markers, were performed at the intensive care unit admission, day 3, day 7, and day 14. The primary outcome was a composite of deep venous thrombosis, pulmonary embolism, and thrombosis at the central catheter insertion sites. We enrolled 70 patients, including 57 patients with COVID-19 and 13 patients without COVID-19, and all patients completed follow-up. The incidence of the primary outcome was higher among patients with COVID-19 than among patients with respiratory failure related to other etiologies (36.8% vs. 0%, p = 0.023). Multivariate regression analysis revealed that VTE was independently associated with a COVID-19 diagnosis (odds ratio: 6.28, 95% confidence interval: 1.19-68.07) and D-dimer concentration (1-ng/mL increase, odds ratio: 1.15, 95% confidence interval: 1.05-1.30). The incidence of VTE was higher among critically ill mechanically ventilated patients, relative to among patients with respiratory failure related to other causes.

Temporal and geographical comparison of bulk tank milk and water microbiota composition in Brazilian dairy farms.

This study investigated the relationship between the bacterial communities of bulk tank milk (BTM) and water used in Brazilian dairy farms. We also explored the association between BTM microbiota and its quality parameters (i.e., somatic cell count [SCC] and total bacteria count [TBC]). Water and BTM samples were collected twice for high throughput metataxonomic characterization. Milk samples were collected for SCCs, TBCs, and antimicrobial residue analysis. Water samples were submitted for physico-chemical and microbiological analyses. Overall, the BTM bacterial community was not influenced by the water microbiota. Furthermore, a higher number of Bacillus spp. and a tendency toward a higher number of Lactococcus spp. was associated with a higher TBC, and consequently could be used as an indicator of milk quality. A higher number of Streptococcus spp. and a tendency toward a higher number of Staphylococcus spp. were associated with a higher SCC. Apart from a variation on the content of the Bacillus taxa, no effect of sampling time on BTM bacterial community was observed. Finally, a negative correlation between the number of different species (richness) on BTM and SCC was found.

Thioridazine inhibits gene expression control of the cell wall signaling pathway (CWI) in the human pathogenic fungus Paracoccidioides brasiliensis.

Paracoccidioides brasiliensis is a thermodimorphic fungus associated with paracoccidioidomycosis (PCM), the most common systemic mycosis in Latin America. PCM treatment involves a long-term chemotherapeutic approach and relapses occur at an alarming frequency. Moreover, the emergence of strains with increased drug-resistance phenotypes puts constant pressure on the necessity to develop new alternatives to treat systemic mycoses. In this work, we show that the phenothiazine (PTZ) derivative thioridazine (TR) inhibits in vitro growth of P. brasiliensis yeasts at micromolar concentrations. We employed microarray hybridization to examine how TR affects gene expression in this fungus, identifying ~1800 genes that were modulated in response to this drug. Dataset evaluation showed that TR inhibits the expression of genes that control the onset of the cell wall integrity (CWI) response, hampering production of all major structural polysaccharides of the fungal cell wall (chitin, α-glucan and ß-glucan). Although TR and other PTZs have been shown to display antimicrobial activity by various mechanisms, inhibition of CWI signaling has not yet been reported for these drugs. Thus, TR may provide a novel approach to treat fungal infections by targeting cell wall biogenesis.

Utility and limitations of APRI and FIB4 to predict staging in a cohort of nonselected outpatients with hepatitis C.

BACKGROUND: Chronic hepatitis C(CHC) staging is important for therapeutic decision-making. Identification of noninvasive markers can provide alternatives to liver biopsy. AIM: To assess the value of APRI and FIB4 for CHC fibrosis staging in a cohort of nonselected outpatients from a referral center in Sao Paulo, Brazil. MATERIAL AND METHODS: Medical records of 798 adult outpatients were analyzed retrospectively. For calculations of APRI and FIB4, the original descriptions were considered, and markers were compared with degree of liver injury. RESULTS: Overall, 49.3% of participants were female, and mean age was 56.9 ± 12.5 years. Genotype 1 was predominant (71.7 vs. 23.7% genotype 3); 64% had significant fibrosis, 44% had advanced fibrosis, and 28% had cirrhosis. The areas under the receiver operating curve for significant fibrosis, advanced fibrosis, and cirrhosis, respectively, were 0.809, 0.819, and 0.815 for the APRI marker and 0.803, 0.836 and 0.852 for FIB4. Using the recommended cut off values, approximately 30-40% of the patients could not be classified. In the remainder, either APRI or FIB4 alone correctly diagnosed 80-85% of cases. Concomitant or consecutive use of both APRI and FIB4 increased the number of the cases correctly diagnosed only slightly, but also increased the number of patients not classified within the cutoff values. CONCLUSIONS: In conclusion, use of the APRI or FIB4 markers for detection of hepatic fibrosis may be a viable alternative at referral centers for treatment of CHC in low- and middle-income countries. Despite relatively good accuracy, a significant number of patients could not be assessed by these methods.

Comparative genomic analysis of coffee-infecting Xylella fastidiosa strains isolated from Brazil.

Strains of Xylella fastidiosa constitute a complex group of bacteria that develop within the xylem of many plant hosts, causing diseases of significant economic importance, such as Pierce's disease in North American grapevines and citrus variegated chlorosis in Brazil. X. fastidiosa has also been obtained from other host plants, in direct correlation with the development of diseases, as in the case of coffee leaf scorch (CLS)--a disease with potential to cause severe economic losses to the Brazilian coffee industry. This paper describes a thorough genomic characterization of coffee-infecting X. fastidiosa strains, initially performed through a microarray-based approach, which demonstrated that CLS strains could be subdivided in two phylogenetically distinct subgroups. Whole-genomic sequencing of two of these bacteria (one from each subgroup) allowed identification of ORFs and horizontally transferred elements (HTEs) that were specific to CLS-related X. fastidiosa strains. Such analyses confirmed the size and importance of HTEs as major mediators of chromosomal evolution amongst these bacteria, and allowed identification of differences in gene content, after comparisons were made with previously sequenced X. fastidiosa strains, isolated from alternative hosts. Although direct experimentation still needs to be performed to elucidate the biological consequences associated with such differences, it was interesting to verify that CLS-related bacteria display variations in genes that produce toxins, as well as surface-related factors (such as fimbrial adhesins and LPS) that have been shown to be involved with recognition of specific host factors in different pathogenic bacteria.

Shifts in plant functional groups along an aridity gradient in a tropical dry forest.

Increasing aridity associated with climate change may lead to the crossing of critical ecosystem thresholds in drylands, compromising ecosystem services for millions of people. In this context, finding tools to detect at early stages the effects of increasing aridity on ecosystems is extremely urgent to avoid irreversible damage. Here, we assess shifts in plant community functional structure along a spatial aridity gradient in tropical dryland (Brazilian Caatinga), to select the most appropriate plant functional groups as ecological indicators likely useful to predict temporal ecosystem trajectories in response to aridity. We identified seven plant functional groups based on 13 functional traits associated with plant establishment, defense, regeneration, and dispersal, whose relative abundances changed, linearly and non-linearly, with increasing aridity, showing either increasing or decreasing trends. Of particular importance is the increase in abundance of plants with high chemical defense and Crassulacean Acid Metabolism (CAM) photosynthetic pathway, with increasing aridity. We propose the use of these functional groups as early warning indicators to detect aridity impacts on these dryland ecosystems and shifts in ecosystem functioning. This information can also be used in the elaboration of mitigation and ecological restoration measures to prevent and revert current and future climate change impacts on tropical dry forests.

Effect of antihypertensive agents on sleep apnea and ambulatory blood pressure in patients with hypertension: A randomized controlled trial.

BACKGROUND: Obstructive sleep apnea (OSA) and hypertension are common conditions that may be linked through sympathetic activation and water retention. We hypothesized that diuretics, which reduce the body water content, may be more effective than amlodipine, a blood pressure (BP)-lowering agent implicated with edema, in controlling OSA in patients with hypertension. We also aimed to compare the effects of these treatments on ambulatory blood pressure monitoring (ABPM). METHODS: In a randomized, double-blind clinical trial, we compared the effects of chlorthalidone/amiloride 25/5 mg with amlodipine 10 mg on OSA measured by portable sleep monitor and BP measured by ABPM. The study included participants older than 40 who had moderate OSA (10-40 apneas/hour of sleep) and BP within the systolic range of 140-159 mmHg or diastolic range of 90-99 mmHg. RESULTS: The individuals in the experimental groups were comparable in age, gender, and other relevant characteristics. Neither the combination of diuretics nor amlodipine alone reduced the AHI after 8 weeks of treatment (AHI 26.3 with diuretics and 25.0 with amlodipine. P = 0.713). Both treatments significantly lowered office, 24-h, and nighttime ABP, but the two groups had no significant difference. CONCLUSION: Chlorthalidone associated with amiloride and amlodipine are ineffective in decreasing the frequency of sleep apnea episodes in patients with moderate OSA and hypertension. Both treatments have comparable effects in lowering both office and ambulatory blood pressure. The notion that treatments could offer benefits for both OSA and hypertension remains to be demonstrated. TRIAL REGISTRATION CLINICALTRIALS. GOV IDENTIFIER: NCT01896661.

Gene expression modulation by paraquat-induced oxidative stress conditions in Paracoccidioides brasiliensis.

Paracoccidioides brasiliensis is a thermodimorphic fungus associated with paracoccidioidomycosis (PCM), the most common systemic mycosis in Latin America. The infection is initiated by inhalation of environmentally dispersed conidia produced by the saprophytic phase of the fungus. In the lungs, P. brasiliensis assumes the parasitic yeast form and must cope with the adverse conditions imposed by cells of the host immune system, which includes a harsh environment, highly concentrated in reactive oxygen species (ROS). In this work, we used the ROS-generating agent paraquat to experimentally simulate oxidative stress conditions in order to evaluate the stress-induced modulation of gene expression in cultured P. brasiliensis yeast cells, using a microarray hybridization approach. The large-scale evaluation inherent to microarray-based analyses identified 2070 genes differentially transcribed in response to paraquat exposure, allowing an integrated visualization of the major metabolic changes that constitute the systemic defense mechanism used by the fungus to overcome the deleterious effects of ROS. These include overexpression of detoxifying agents, as well as of molecular scavengers and genes involved in maintenance of the intracellular redox potential. Particularly noteworthy was to verify that the oxidative stress resistance mechanism of P. brasiliensis also involves coordinated overexpression of a series of genes responsible for chitin-biosynthesis, suggesting that this pathway may constitute a specific regulon. Further analyses aiming at confirming and understanding the mechanisms that control such regulon may provide interesting new targets for chemotherapeutic approaches against P. brasiliensis and other pathogenic fungi.

Prognostic value of Doppler waveform analysis of common femoral vein in septic patients: a prospective cohort study.

OBJECTIVES: To assess whether there is an association between abnormal common femoral vein (CFV) Doppler waveform and intensive care unit (ICU) mortality in patients with sepsis. METHODS: Patients admitted to the ICU with sepsis were included. Pulsed-wave Doppler was performed by examining the CFV in the short axis without angle correction and in the long axis with angle correction. An abnormal CFV Doppler waveform was determined by a retrograde velocity peak (RVP) > 10 cm/s in the long axis or RVP > 50% of the antegrade velocity peak in the short axis. TAPSE < 17 mm was defined as right ventricular (RV) dysfunction. The primary outcome was ICU mortality. RESULTS: One hundred and ten patients were included. There was no association between abnormal CFV Doppler waveforms in the long (p = 0.709) and short axes (p = 0.171) and ICU mortality. TAPSE measurements were performed in 16 patients. RV dysfunction was identified in 8 (50.0%) patients. There was no association between the diagnosis of RV dysfunction based on TAPSE measurement and the identification of abnormal CFV Doppler waveforms in the long axis (p = 1.000) and in the short axis (p = 1.000). CONCLUSION: Abnormal CFV Doppler waveforms were not associated with ICU mortality in patients with sepsis. Furthermore, in the exploratory analysis, these alterations were not useful in identifying RV dysfunction in these patients.

Nitrate supply decreases fermentation and alleviates oxidative and ionic stress in nitrogen-fixing soybean exposed to saline waterlogging.

Nitrate (NO3 - ) nutrition is known to mitigate the damages caused by individual stresses of waterlogging and salinity. Here, we investigated the role of NO3 - in soybean plants exposed to these stresses in combination. Nodulated soybean cultivated under greenhouse conditions and daily fertilised with a nutrient solution without nitrogen were subjected to the following treatments: Water, NO3 - , NaCl, and NaCl+NO3 - . Then, plants were exposed to waterlogging (6days) and drainage (2days). Compared to plants exposed to isolated stress, the saline waterlogging resulted in higher concentrations of H2 O2 , O2 ˙- , and lipid peroxidation at the whole-plant level, mainly during drainage. Furthermore, saline waterlogging increased fermentation and the concentrations of Na+ and K+ in roots and leaves both during waterlogging and drainage. NO3 - supplementation led to augments in NO3 - and NO levels, and stimulated nitrate reductase activity in both organs. In addition, NO3 - nutrition alleviated oxidative stress and fermentation besides increasing the K+ /Na+ ratio in plants exposed to saline waterlogging. In conclusion, NO3 - supplementation is a useful strategy to help soybean plants overcome saline waterlogging stress. These findings are of high relevance for agriculture as soybean is an important commodity and has been cultivated in areas prone to saline waterlogging.

The bovine leukemia virus infection prolongs immunosuppression in dairy cows during the periparturient period by sustaining higher expression of immunological checkpoints in T cells.

Bovine leukemia virus (BLV) is caused by a deltaretrovirus and has been associated with immunosuppression as well as comorbidities such as bovine mastitis, the costliest disease in the dairy sector. However, no previous study has explored at the synergistic immunosuppressive effect of the peripartum period with an immunosuppressive viral disease such as BLV. Thus, our study explored the effect of BLV infection in the periparturient period on the expression of PD-1 and CTLA-4 in blood T lymphocytes, and the impact of BLV infection on the rate of new intramammary infections during the early lactation. Here, we found that BLV-infected dairy cows always had a statistically significant higher expression of CTLA-4 and PD-1 in blood T cells. Furthermore, our findings indicated that BLV infection prolongs immunosuppression in dairy cows during the periparturient period by sustaining higher expression of immunological checkpoints in T cells. In addition, BLV-infected dairy cows have a higher rate of new intramammary infections during early lactation. Thus, our study provides new insights of the immunosuppressive effect of BLV on the most critical period of the cows' life with marked detrimental effect on protective T-cell immunity and comorbidities, such as bovine mastitis.