The scene of lung pathology during PRRSV-1 infection.

Porcine reproductive and respiratory syndrome (PRRS) is one of the most economically important infectious diseases for the pig industry worldwide. The disease was firstly reported in 1987 and became endemic in many countries. Since then, outbreaks caused by strains of high virulence have been reported several times in Asia, America and Europe. Interstitial pneumonia, microscopically characterised by thickened alveolar septa, is the hallmark lesion of PRRS. However, suppurative bronchopneumonia and proliferative and necrotising pneumonia are also observed, particularly when a virulent strain is involved. This raises the question of whether the infection by certain strains results in an overstimulation of the proinflammatory response and whether there is some degree of correlation between the strain involved and a particular pattern of lung injury. Thus, it is of interest to know how the inflammatory response is modulated in these cases due to the interplay between virus and host factors. This review provides an overview of the macroscopic, microscopic, and molecular pathology of PRRSV-1 strains in the lung, emphasising the differences between strains of different virulence.

Macrophage polarization in lymph node granulomas from cattle and pigs naturally infected with Mycobacterium tuberculosis complex.

Tuberculosis in animals is caused by members of the Mycobacterium tuberculosis complex (MTC), with the tuberculous granuloma being the main characteristic lesion. The macrophage is the main cell type involved in the development of the granuloma and presents a wide plasticity ranging from polarization to classically activated or pro-inflammatory macrophages (M1) or to alternatively activated or anti-inflammatory macrophages (M2). Thus, this study aimed to analyze macrophage polarization in granulomas from cattle and pig lymph nodes naturally infected with MTC. Tuberculous granulomas were microscopically categorized into four stages and a panel of myeloid cells (CD172a/calprotectin), M1 macrophage polarization (iNOS/CD68/CD107a), and M2 macrophage polarization (Arg1/CD163) markers were analyzed by immunohistochemistry. CD172a and calprotectin followed the same kinetics, having greater expression in late-stage granulomas in pigs. iNOS and CD68 had higher expression in cattle compared with pigs, and the expression was higher in early-stage granulomas. CD107a immunolabeling was only observed in porcine granulomas, with a higher expression in stage I granulomas. Arg1+ cells were significantly higher in pigs than in cattle, particularly in late-stage granulomas. Quantitative analysis of CD163+ cells showed similar kinetics in both species with a consistent frequency of immunolabeled cells throughout the different stages of the granuloma. Our results indicate that M1 macrophage polarization prevails in cattle during early-stage granulomas (stages I and II), whereas M2 phenotype is observed in later stages. Contrary, and mainly due to the expression of Arg1, M2 macrophage polarization is predominant in pigs in all granuloma stages.

Diagnostic performance of faecal and tissue multiplex qPCR IS900/F57 for the detection of Mycobacterium avium subspecies paratuberculosis in cattle.

Mycobacterium avium subspecies paratuberculosis (MAP) is responsible for bovine-paratuberculosis (bPTB), which causes high production losses in cattle. A cross-sectional study was conducted in 228 cattle to evaluate the validity and diagnostic utility of a multiplex real-time PCR (qPCR) on faecal and intestinal samples [ileocaecal valve (ICV) and ileocaecal lymph nodes (ICLN)], using intestinal tissue culture as a reference test. Based on the sensitivity, specificity, and likelihood ratios (LR) obtained, the diagnostic value of faecal qPCR for confirming MAP infection was moderate (sensitivity 50.3%, specificity 93.5%, positive LR 7.8), and low to rule it out (negative LR 0.5). In areas with a prevalence of >23% the credibility of positive results was higher than 70%. In the case of negative results, their credibility was higher than 90% in herds with an infection rate below 19%, so faecal qPCR would be very useful in these areas to certify the absence of infection. For post-mortem diagnosis, qPCR on ICV samples showed good diagnostic accuracy to confirm the disease (sensitivity 71.7%, specificity 93.3%, positive LR 10.8), with a credibility higher than 70% in animals from areas or herds with a prevalence of infection greater than or equal to 18%. The best strategy to rule out the disease was the parallel combination of both tissues (ICV + ICLN) (sensitivity 81.3%, specificity 89.5%, negative LR 0.2) with a credibility of over 95% in animals from areas with an infection prevalence of 0-20%. Faecal and tissues qPCR techniques can be used to monitor bPTB, the interpretation of results, according to epidemiological situation of the herd or area, are shown.

Impact of supplementation with dihydroxylated vitamin D3 on performance parameters and gut health in weaned Iberian piglets under indoor/outdoor conditions.

BACKGROUND: Vitamin D may improve innate antimicrobial response and the integrity of the intestinal mucosal barrier representing an alternative to antibiotics for improving pig health. Therefore, benefits of dietary supplementation with a product based on vitamin D3 metabolite-rich plant extracts were assessed in 252 purebred Iberian piglets for a period of 60 days. The study group received 1,25 dihydroxyvitamin D (1,25(OH)2D) (100 ppm) in the conventional feed, which already included vitamin D (2000 IU in the starter and 1000 IU in the adaptation diets, respectively). Average daily gain (ADG), feed conversion ratio (FCR) and coefficient of variation of body weight (CV-BW) were assessed along the study. Blood samples, from 18 animals of the study group and 14 animals of the control group, were collected at selected time points to determine white blood cell count, concentration of vitamin D3 and its metabolites, and IgA and IgG in serum. Histopathology, morphometry, and immunohistochemistry (IgA and FoxP3) from small intestine samples were performed on days 30 and 60 of the study from 3 animals per group and time point. RESULTS: The ADG (493 vs 444 g/day) and FCR (2.3 vs 3.02) showed an improved performance in the supplemented animals. Moreover, the lower CV-BW indicated a greater homogeneity in the treated batches (13.17 vs 26.23%). Furthermore, a mild increase of IgA and in the number of regulatory T cells in the small intestine were observed in treated pigs. CONCLUSIONS: These results highlight the benefits of this supplementation and encourage to develop further studies along other production stages.

Muscle glycogen unavailability and fat oxidation rate during exercise: Insights from McArdle disease.

Carbohydrate availability affects fat metabolism during exercise; however, the effects of complete muscle glycogen unavailability on maximal fat oxidation (MFO) rate remain unknown. Our purpose was to examine the MFO rate in patients with McArdle disease, comprising an inherited condition caused by complete blockade of muscle glycogen metabolism, compared to healthy controls. Nine patients (three women, aged 36 ± 12 years) and 12 healthy controls (four women, aged 40 ± 13 years) were studied. Several molecular markers of lipid transport/metabolism were also determined in skeletal muscle (gastrocnemius) and white adipose tissue of McArdle (Pygm p.50R*/p.50R*) and wild-type male mice. Peak oxygen uptake ( V ̇ O 2 peak ${\dot V_{{{\rm{O}}_{\rm{2}}}{\rm{peak}}}}$ ), MFO rate, the exercise intensity eliciting MFO rate (FATmax) and the MFO rate-associated workload were determined by indirect calorimetry during an incremental cycle-ergometer test. Despite having a much lower V ̇ O 2 peak ${\dot V_{{{\rm{O}}_{\rm{2}}}{\rm{peak}}}}$ (24.7 ± 4 vs. 42.5 ± 11.4 mL kg-1  min-1 , respectively; P < 0.0001), patients showed considerably higher values for the MFO rate (0.53 ± 0.12 vs. 0.33 ± 0.10 g min-1 , P = 0.001), and for the FATmax (94.4 ± 7.2 vs. 41.3 ± 9.1 % of V ̇ O 2 peak ${\dot V_{{{\rm{O}}_{\rm{2}}}{\rm{peak}}}}$ , P < 0.0001) and MFO rate-associated workload (1.33 ± 0.35 vs. 0.81 ± 0.54 W kg-1 , P = 0.020) than controls. No between-group differences were found overall in molecular markers of lipid transport/metabolism in mice. In summary, patients with McArdle disease show an exceptionally high MFO rate, which they attained at near-maximal exercise capacity. Pending more mechanistic explanations, these findings support the influence of glycogen availability on MFO rate and suggest that these patients develop a unique fat oxidation capacity, possibly as an adaptation to compensate for the inherited blockade in glycogen metabolism, and point to MFO rate as a potential limiting factor of exercise tolerance in this disease. KEY POINTS: Physically active McArdle patients show an exceptional fat oxidation capacity. Maximal fat oxidation rate occurs near-maximal exercise capacity in these patients. McArdle patients' exercise tolerance might rely on maximal fat oxidation rate capacity. Hyperpnoea might cloud substrate oxidation measurements in some patients. An animal model revealed overall no higher molecular markers of lipid transport/metabolism.

Fat Oxidation during Exercise in People with Spinal Cord Injury, and Protocols Used: A Systematic Review.

BACKGROUND: The aim of this study was to summarize evidence on energy metabolism through peak fat oxidation (PFO) and maximum fat oxidation (Fatmax), as well as to analyze the protocols used in people with spinal cord injury (SCI) and to examine the main factors related to fat oxidation ability (i.e., age, sex, level of physical activity, and level and degree of injury). METHODS: Studies to determine PFO and Fatmax using indirect calorimetry with an arm exercise protocol for SCI patients were included after a systematic search. Other endpoints included study design, sample size, control group, demographic data, level of injury, physical condition, protocol, outcomes measured, and statistical findings. RESULTS: Eight studies (n = 560) were included. The mean value of VO2peak was 1.86 L∙min-1 (range 0.75-2.60 L∙min-1) (lowest value in the tetraplegic subjects). The PFO ranged between 0.06 and 0.30 g∙min-1 (lowest rates: the non-trained subjects with cervical SCI; highest: the tetraplegic subjects). Two types of exercise protocol were found: arm cycle ergometer, and wheelchair propulsion with a computerized ergometer. Five studies used an incremental protocol (2-3 min/stage, different load increments); the rest performed tests of 20 min/stage at three intensities. CONCLUSION: There are few existing studies measuring fat oxidation in SCI, many of which used small and heterogeneous samples. PFO was lower in SCI subjects when compared with non-injured people performing lower-limb exercise; however, comparing upper-limb exercise, people with SCI showed higher values.

Comparison of the efficacy of two alveolar recruitment manoeuvres in improving the lung mechanics and the degree of atelectasis in anaesthetized healthy sheep.

The aim of the present study was to evaluate whether the application of two types of alveolar recruitment manoeuvres (ARMs) followed by a positive end-expiratory pressure (PEEP) improved lung mechanics and the degree of atelectasis caused by general anaesthesia. Twenty-one female Merino sheep were divided into three groups: sustained inflation ARM (ARMsust), stepwise ARM (AMRstep), and control (without ARM). Sheep received detomidine-morphine for premedication, propofol for induction, and isoflurane during general anaesthesia in a volume-controlled mode with 100% oxygen during the first 15 min of anaesthesia and 40% the rest of the study. The right jugular vein and metacarpal artery were catheterised for mixed venous and arterial blood sample collection, respectively. The quasistatic compliance (Cqst), oxygenation parameters, and shunt fraction (Qs/Qt) were monitored before ARM application (TpreARM), and at 10 (T10) and 60 min (T60) after ARM application. A pulmonary histopathological study was conducted on five animals from each group. A significant increase in Cqst was observed in both ARM groups at T10 compared to TpreARM (ARMsust: P = 0.001; ARMstep: P = 0.002), although only the ARMsust group showed significant differences compared to the control group. The ARMstep group presented a significant improvement in oxygenation parameters and Qs/Qt fraction (T10: 4.84 (3.26-16.48)%, P = 0.048; T60: 4.40 (4.31-14.16)%, P = 0.004) compared with TpreARM (21.48 (20.61-28.32)%). The ARMstep group had the highest percentage of alveolar area and the most homogeneous values. In conclusion, the application of a stepwise ARM followed by PEEP improved atelectasis caused by isoflurane anaesthesia in healthy sheep.

The Role of Histopathology as a Complementary Diagnostic Tool in the Monitoring of Bovine Tuberculosis.

The diagnosis of bovine tuberculosis (bTB) is based on the single intradermal tuberculin test (SIT), interferon gamma, and compulsory slaughter of reactor animals. Culture and PCR from fresh tissue are regarded as gold standard techniques for post-mortem confirmation, with the former being time-consuming and presenting moderate to low sensitivity and the latter presenting promising results. Histopathology has the advantage to identify and categorize lesions in both reactor and non-reactor animals. Therefore, this study aims to highlight the role of histopathology in the systematic diagnosis of bTB to shorten the time to disclose positive animals. Blood (212) and lymph node (681) samples were collected for serological, bacteriological, and histopathological analyses from a total of 230 cattle subjected to the Spanish bTB eradication program. Seventy-one lymph nodes and 59 cattle yielded a positive result to bacteriology, with 59 lymph nodes and 48 cattle presenting a positive result in real-time PCR from fresh tissue. Roughly 19% (40/212) of sera samples gave a positive result to ELISA. Tuberculosis-like lesions (TBLs) were observed in 11.9% (81/681) of the lymph nodes and 30.9% (71/230) of cattle. Noteworthy, TBLs were evidenced in 18 out of 83 SIT- and real-time PCR and bacteriology negative animals, with 11/18 disclosing a positive result to Ziehl-Neelsen technique and two of them to ddPCR from paraffin blocks targeting IS6110. Six out of these 11 ZN+ corresponded with mesenteric LN and were confirmed positive to paratuberculosis. Histopathology yielded a sensitivity of 91.3% (CI95 83.2-99.4%) and a specificity of 84.4% (CI95 78.6-89.3%) with good agreement (κ = 0.626) when compared with real-time PCR. Our results confirm that histopathology allows a rapid confirmation of real-time PCR and bacteriology, emphasizing its contribution to bTB control and monitoring.

Long-Term Exercise Intervention in Patients with McArdle Disease: Clinical and Aerobic Fitness Benefits.

INTRODUCTION: The long-term effects of exercise in patients with McArdle disease-the paradigm of "exercise intolerance"-are unknown. This is an important question because the severity of the disease frequently increases with time. PURPOSE: This study aimed to study the effects of a long-term exercise intervention on clinical and fitness-related outcomes in McArdle patients. METHODS: Seventeen patients (exercise group: n = 10, 6 male, 38 ± 18 yr; control: n = 7, 4 male, 38 ± 18 yr) participated in a 2-yr unsupervised intervention including moderate-intensity aerobic (cycle-ergometer exercise for 1 h) and resistance (high load-low repetition circuit) training on 5 and 2-3 d·wk -1 , respectively. Patients were assessed at baseline and postintervention. Besides safety, outcomes included clinical severity (e.g., exercise intolerance features) on a 0-3 scale (primary outcome), and aerobic fitness, gross muscle efficiency, and body composition (total/regional fat, muscle, and bone mass; secondary outcomes). RESULTS: The exercise program was safe and resulted in a reduction of 1 point (-1.0; 95% confidence interval, -1.6 to -0.5; P = 0.025) in clinical severity versus the control group, with 60% of participants in the exercise group becoming virtually asymptomatic and with no functional limitation in daily life activities. Compared with controls, the intervention induced significant and large benefits (all P < 0.05) in the workload eliciting the ventilatory threshold (both in absolute (watts, +37%) and relative units (watts per kilogram of total body mass or of lower-limb muscle mass, +44%)), peak oxygen uptake (in milliliters per kilogram per minute, +28%), and peak workload (in absolute (+27%) and relative units (+33%)). However, no significant changes were found for muscle efficiency or for any measure of body composition. CONCLUSIONS: A 2-yr unsupervised intervention including aerobic and resistance exercise is safe and induces major benefits in the clinical course and aerobic fitness of patients with McArdle disease.

The medium-term consequences of a COVID-19 lockdown on lifestyle among Spanish older people with hypertension, pulmonary disease, cardiovascular disease, musculoskeletal disease, depression, and cancer.

OBJECTIVES: This study investigated the associations of chronic diseases with changes in lifestyle and health behaviours in older people following the coronavirus disease 2019 (COVID-19) lockdown in Spain and compared the differences in changes over time. METHODS: 1,092 participants (80.3±5.6 years; 66.5% female) from 2 Spanish cohorts were included. Telephone-based questionnaires were conducted to evaluate lifestyle and health risk behaviours at the end of lockdown and 7 months post-lockdown. Participants were classified as having physician-diagnosed chronic diseases based on self-reported data. Cox proportional models adjusted for major confounders were used. RESULTS: Compared to those without the corresponding chronic diseases, older people with hypertension were less likely to report increased alcohol consumption (hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.55 to 0.99). Pulmonary diseases were associated with lower risks of increased sedentary time (HR, 0.58; 95% CI, 0.39 to 0.86) and worsened sleep quality (HR, 0.56; 95% CI, 0.36 to 0.87), while cardiovascular diseases were associated with a lower risk of decreased sedentary time (HR, 0.58; 95% CI, 0.38 to 0.88). Depression was linked to a higher likelihood of improved diet quality (HR, 1.53; 95% CI, 1.00 to 2.36). Cancer pacients were less likely to have worsened sleep quality (HR, 0.44; 95% CI, 0.22 to 0.89) but more likely to have reduced their frequency of social contact (HR, 2.05; 95% CI, 1.05 to 3.99). CONCLUSIONS: Older people with chronic diseases showed beneficial changes in lifestyle and health risk behaviours after the COVID-19 lockdown. In particular, older people with hypertension, pulmonary disease, and cancer tended to make beneficial lifestyle and health behaviour changes. However, older people with cardiovascular disease and depression engaged in more health risk behaviours.

Osteoporosis and Its Association With Cardiovascular Disease, Respiratory Disease, and Cancer: Findings From the UK Biobank Prospective Cohort Study.

OBJECTIVE: To investigate sex-specific associations of osteoporosis with incidence of and mortality from cardiovascular disease (CVD), respiratory disease, and cancer as well as with all-cause mortality. METHODS: In total, 305,072 participants (53% [161,383] women) of UK Biobank were included in this study (2007-2010). Self-reported diagnosis of osteoporosis at baseline was the exposure of interest. The outcomes were CVD, respiratory disease, chronic obstructive pulmonary disease (COPD), all cancer, and prostate and breast cancer incidence and mortality and all-cause mortality. Associations between osteoporosis and outcomes were investigated using Cox proportional hazards models. RESULTS: In men, osteoporosis was associated with a higher incident risk of all respiratory diseases (hazard ratio [HR], 1.26; 95% CI, 1.06 to 1.50) including COPD (HR, 1.82; 95% CI, 1.38 to 2.40). Men with osteoporosis also had a higher mortality risk from all causes (HR, 1.71; 95% CI, 1.38 to 2.11), CVD (HR, 1.68; 95% CI, 1.19 to 2.37), respiratory disease (HR, 2.35; 95% CI, 1.70 to 3.24), and COPD (HR, 3.64; 95% CI, 2.24 to 5.91). These associations persisted after adjustment for age, body mass index, and comorbidities. Women with osteoporosis had a higher risk of incident CVD (HR, 1.24; 95% CI, 1.97 to 1.44), respiratory disease (HR, 1.23; 95% CI, 1.13 to 1.33), and COPD (HR, 1.29; 95% CI, 1.10 to 1.52). Women with osteoporosis also had a higher mortality risk from respiratory disease (HR, 1.31; 95% CI, 1.00 to 1.72) and breast cancer (HR, 1.60; 95% CI, 1.14 to 2.26). CONCLUSION: Compared with women, men with osteoporosis had a higher risk of all-cause mortality, mortality from respiratory diseases including COPD, and cancer incidence. Osteoporosis was strongly associated with respiratory disease and COPD in both sexes, even after full adjustment for covariates, although men with osteoporosis experienced a higher risk of adverse outcomes.

PRRSV-1 induced lung lesion is associated with an imbalance between costimulatory and coinhibitory immune checkpoints.

Porcine reproductive and respiratory syndrome virus (PRRSV) induces a dysregulation on the innate and adaptive immune responses. T-cell activation requires a proper interaction and precise balance between costimulatory and coinhibitory molecules, commonly known as immune checkpoints. This study aims to evaluate the expression of immune checkpoints in lung and tracheobronchial lymph node from piglets infected with two PRRSV-1 strains of different virulence during the early stage of infection. Seventy 4-week-old piglets were grouped into three experimental groups: (i) control, (ii) 3249-infected group (low virulent strain), and (iii) Lena-infected group (virulent strain) and were euthanized at 1, 3, 6, 8, and 13 days post-infection (dpi). Lung and tracheobronchial lymph node were collected to evaluate histopathological findings, PRRSV viral load and mRNA expression of costimulatory (CD28, CD226, TNFRSF9, SELL, ICOS, and CD40) and coinhibitory (CTLA4, TIGIT, PD1/PDL1, TIM3, LAG3, and IDO1) molecules through RT-qPCR. Our findings highlight a mild increase of costimulatory molecules together with an earlier and stronger up-regulation of coinhibitory molecules in both organs from PRRSV-1-infected animals, especially in the lung from virulent Lena-infected animals. The simultaneous expression of coinhibitory immune checkpoints could work in synergy to control and limit the inflammation-induced tissue damage. Further studies should be addressed to determine the role of these molecules in later stages of PRRSV infection.

Increased Fat Oxidation During Arm Cycling Exercise in Adult Men With Spinal Cord Injury Compared With Noninjured Controls.

People with spinal cord injury (SCI) tend to be more sedentary and increase fat accumulation, which could have a negative influence on metabolic flexibility. The aim of this study was to investigate the capacity to oxidize fat in a homogenous sample of men with thoracic SCI compared with healthy noninjured men during an arm cycling incremental test. Forty-one men, 21 with SCI and 20 noninjured controls, performed an incremental arm cycling test to determine peak fat oxidation (PFO) and the intensity of exercise that elicits PFO (Fatmax). PFO was expressed in absolute values (g/min) and relative to whole-body and upper-body lean mass ([mg·min-1]·kg-1) through three different models (adjusting by cardiorespiratory fitness and fat mass). Gross mechanical efficiency was also calculated. PFO was higher in SCI than in noninjured men (0.27 ± 0.07 vs. 0.17 ± 0.07 g/min; 5.39 ± 1.30 vs. 3.29 ± 1.31 [mg·min-1]·kg-1 whole-body lean mass; 8.28 ± 2.11 vs. 5.08 ± 2.12 [mg·min-1]·kg-1 upper-body lean mass). Fatmax was found at a significantly higher percentage of VO2peak in men with SCI (33.6% ± 8.2% vs. 23.6% ± 6.4%). Differences persisted and even increased in the fully adjustment model and at any intensity. Men with SCI showed significantly higher gross mechanical efficiency at 35 and 65 W than the noninjured group. Men with SCI showed higher fat oxidation when compared with noninjured men at any intensity, even increased after full adjustment for lean mass, fat mass, and cardiorespiratory fitness. These findings suggest that SCI men could improve their metabolic flexibility and muscle mass for greater efficiency, not being affected by their fat accumulation.

Fitness vs Fatness as Determinants of Survival in Noninstitutionalized Older Adults: The EXERNET Multicenter Study.

BACKGROUND: Physical fitness and body composition are important health indicators; nevertheless, their combined pattern interrelationships and their association with mortality are poorly investigated. METHODS: This longitudinal study is part of the Spanish EXERNET-Elder project. Person-months of follow-up were calculated from the interview date, performed between June 2008 and November 2009, until the date of death or censoring on March 2018 (whichever came first). In order to be included, participants had to fulfill the following criteria: (a) be older than 65 years, (b) live independently at home, (c) not suffer dementia and/or cancer, and (d) have a body mass index above 18.5. Body fat and weight were assessed by a bioelectrical impedance analyzer. Fitness was measured with the Senior Fitness and the one-leg static balance tests. The Spanish Death Index was consulted for the death's identification. Cluster analysis was performed to identify Fat-Fit patterns and traditional cut-points and percentiles to create the Fat-Fit groups. Cox proportional hazards regression models were used to calculate the hazard ratios (HRs) of death in clustered Fat-Fit patterns and in traditional Fat-Fit groups. RESULTS: A total of 2299 older adults (76.8% of women) were included with a baseline mean age of 71.9 ± 5.2 years. A total of 196 deaths (8.7% of the sample) were identified during the 8 years of follow-up. Four clustered Fat-Fit patterns (Low fat-Fit, Medium fat-Fit, High fat-Unfit, and Low fat-Unfit) and 9 traditional Fat-Fit groups emerged. Using the Low fat-Fit pattern as the reference, significantly increased mortality was noted in High fat-Unfit (HR: 1.68, CI: 1.06-2.66) and Low fat-Unfit (HR: 2.01, CI: 1.28-3.16) groups. All the traditional Fit groups showed lower mortality risk when compared to the reference group (obese-unfit group). CONCLUSION: Physical fitness is a determinant factor in terms of survival in community-dwelling older adults, independently of adiposity levels.

Association of accelerometer-derived step volume and intensity with hospitalizations and mortality in older adults: A prospective cohort study.

PURPOSE: This study aimed to examine the associations of accelerometer-derived steps volume and intensity with hospitalizations and all-cause mortality in older adults. METHODS: This prospective cohort study involved 768 community-dwelling Spanish older adults (78.8 ± 4.9 years, mean ± SD; 53.9% females) from the Toledo Study for Healthy Aging (2012-2017). The number of steps per day and step cadence (steps/min) were derived from a hip-mounted accelerometer worn for at least 4 days at baseline. Participants were followed-up over a mean period of 3.1 years for hospitalization and 5.7 years for all-cause mortality. Cox proportional hazards regression models were used to estimate the individual and joint associations between daily steps and stepping intensity with hospitalizations and all-cause mortality. RESULTS: Included participants walked 5835 ± 3445 steps/day with an intensity of 7.3 ± 4.1 steps/min. After adjusting for age, sex, body mass index (BMI), education, income, marital status and comorbidities, higher step count (hazard ratio (HR) = 0.95, 95% confidence interval (95%CI: 0.90-1.00, and HR = 0.87, 95%CI: 0.81-0.95 per additional 1000 steps) and higher step intensity (HR = 0.95, 95%CI: 0.91-0.99, and HR = 0.89, 95%CI: 0.84-0.95 per each additional step/min) were associated with fewer hospitalizations and all-cause mortality risk, respectively. Compared to the group having low step volume and intensity, individuals in the group having high step volume and intensity had a lower risk of hospitalization (HR = 0.72, 95%CI: 0.52-0.98) and all-cause mortality (HR = 0.60, 95%CI: 0.37-0.98). CONCLUSION: Among older adults, both high step volume and step intensity were significantly associated with lower hospitalization and all-cause mortality risk. Increasing step volume and intensity may benefit older people.

Porcine reproductive and respiratory syndrome virus impacts on gut microbiome in a strain virulence-dependent fashion.

Porcine reproductive and respiratory syndrome (PRRS) is a viral disease defined by reproductive problems, respiratory distress and a negative impact on growth rate and general condition. Virulent PRRS virus (PRRSV) strains have emerged in the last years with evident knowledge gaps in their impact on the host immune response. Thus, the present study examines the impact of acute PRRS virus (PRRSV) infection, with two strains of different virulence, on selected immune parameters and on the gut microbiota composition of infected pigs using 16S rRNA compositional sequencing. Pigs were infected with a low virulent (PRRS_3249) or a virulent (Lena) PRRSV-1 strain and euthanized at 1, 3, 6, 8 or 13 days post-inoculation (dpi). Faeces were collected from each animal at the necropsy time-point. Alpha and beta diversity analyses demonstrated that infection, particularly with the Lena strain, impacted the microbiome composition from 6 dpi onwards. Taxonomic differences revealed that infected pigs had higher abundance of Treponema and Methanobrevibacter (FDR < 0.05). Differences were more considerable for Lena- than for PRRS_3249-infected pigs, showing the impact of strain virulence in the intestinal changes. Lena-infected pigs had reduced abundancies of anaerobic commensals such as Roseburia, Anaerostipes, Butyricicoccus and Prevotella (P < 0.05). The depletion of these desirable commensals was significantly correlated to infection severity measured by viraemia, clinical signs, lung lesions and immune parameters (IL-6, IFN-γ and Hp serum levels). Altogether, the results from this study demonstrate the indirect impact of PRRSV infection on gut microbiome composition in a strain virulence-dependent fashion and its association with selected immune markers.

Activation of T-bet, FOXP3, and EOMES in Target Organs From Piglets Infected With the Virulent PRRSV-1 Lena Strain.

Transcription factors (TFs) modulate genes involved in cell-type-specific proliferative and migratory properties, metabolic features, and effector functions. Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most important pathogen agents in the porcine industry; however, TFs have been poorly studied during the course of this disease. Therefore, we aimed to evaluate the expressions of the TFs T-bet, GATA3, FOXP3, and Eomesodermin (EOMES) in target organs (the lung, tracheobronchial lymph node, and thymus) and those of different effector cytokines (IFNG, TNFA, and IL10) and the Fas ligand (FASL) during the early phase of infection with PRRSV-1 strains of different virulence. Target organs from mock-, virulent Lena-, and low virulent 3249-infected animals humanely euthanized at 1, 3, 6, 8, and 13 days post-infection (dpi) were collected to analyze the PRRSV viral load, histopathological lesions, and relative quantification through reverse transcription quantitative PCR (RT-qPCR) of the TFs and cytokines. Animals belonging to both infected groups, but mainly those infected with the virulent Lena strain, showed upregulation of the TFs T-bet, EOMES, and FOXP3, together with an increase of the cytokine IFN-γ in target organs at the end of the study (approximately 2 weeks post-infection). These results are suggestive of a stronger polarization to Th1 cells and regulatory T cells (Tregs), but also CD4+ cytotoxic T lymphocytes (CTLs), effector CD8+ T cells, and γδT cells in virulent PRRSV-1-infected animals; however, their biological functionality should be the object of further studies.

Cross-sectional and prospective associations of sleep, sedentary and active behaviors with mental health in older people: a compositional data analysis from the Seniors-ENRICA-2 study.

BACKGROUND: Most studies on the effects of sleep, sedentary behavior (SB), and physical activity (PA) on mental health did not account for the intrinsically compositional nature of the time spent in several behaviors. Thus, we examined the cross-sectional and prospective associations of device-measured compositional time in sleep, SB, light PA (LPA) and moderate-to-vigorous PA (MVPA) with depression symptoms, loneliness, happiness, and global mental health in older people (≥ 65 years). METHODS: Data were taken from the Seniors-ENRICA-2 study, with assessments in 2015-2017 (wave 0) and 2018-2019 (wave 1). Time spent in sleep, SB, LPA and MVPA was assessed by wrist-worn accelerometers. Depression symptoms, loneliness, happiness, and global mental health were self-reported using validated questionnaires. Analyses were performed using a compositional data analysis (CoDA) paradigm and adjusted for potential confounders. RESULTS: In cross-sectional analyses at wave 0 (n = 2489), time-use composition as a whole was associated with depression and happiness (all p < 0.01). The time spent in MVPA relative to other behaviors was beneficially associated with depression (γ = -0.397, p < 0.001), loneliness (γ = -0.124, p = 0.017) and happiness (γ = 0.243, p < 0.001). Hypothetically, replacing 30-min of Sleep, SB or LPA with MVPA was beneficially cross-sectionally related with depression (effect size [ES] ranged -0.326 to -0.246), loneliness (ES ranged -0.118 to -0.073), and happiness (ES ranged 0.152 to 0.172). In prospective analyses (n = 1679), MVPA relative to other behaviors at baseline, was associated with favorable changes in global mental health (γ = 0.892, p = 0.049). We observed a beneficial prospective effect on global mental health when 30-min of sleep (ES = 0.521), SB (ES = 0.479) or LPA (ES = 0.755) were theoretically replaced for MVPA. CONCLUSIONS: MVPA was cross-sectionally related with reduced depression symptoms and loneliness and elevated level of happiness, and prospectively related with enhanced global mental health. Compositional isotemporal analyses showed that hypothetically replacing sleep, SB or LPA with MVPA could result in modest but significantly improvements on mental health indicators. Our findings add evidence to the emerging body of research on 24-h time-use and health using CoDA and suggest an integrated role of daily behaviors on mental health in older people.

Association of sarcopenia with incident osteoporosis: a prospective study of 168,682 UK biobank participants.

BACKGROUND: Sarcopenia often co-occurs with osteoporosis in cross-sectional studies. However, this association has rarely been studied in prospective studies. This study aimed to investigate the association between sarcopenia categories-along with its individual components-and incident osteoporosis in both middle-aged and older men and women from the UK Biobank study. METHODS: A total of 168,682 participants (48.8% women, aged 37 to 70 years at baseline) were included in this prospective study. Categories of sarcopenia (pre-sarcopenia and sarcopenia), and its individual components, were defined according to the EWGSOP2 criteria (2019). Associations with incident osteoporosis by sex were investigated using Cox-proportional hazard models adjusted for socio-demographic, lifestyle and health-related factors, and morbidity count. Associations between categories of sarcopenia and incident osteoporosis were also investigated by age-groups and subtype of osteoporosis (with and without pathological fractures). RESULTS: After a median follow-up of 7.4 years, 6296 participants were diagnosed with osteoporosis. When the analyses were adjusted for a range of relevant confounding factors, pre-sarcopenia was associated with 1.3-times higher risk of osteoporosis in men (HR: 1.30 [95% CI: 1.03 to 1.63]) but not in women, and sarcopenia was associated with 1.66-times increased osteoporosis risk in women (HR: 1.66 [95% CI: 1.33 to 2.08]) but not in men compared with people without sarcopenia or pre-sarcopenia. A similar magnitude of associations was found in osteoporosis without pathological fractures but weaker for those with pathological fractures. Within the individual components, low muscle mass (HRwomen : 1.36 [95% CI: 1.22 to 1.51] and HRmen : 3.07 [95% CI: 1.68 to 5.59]), followed by slow gait speed (HRwomen : 1.30 [95% CI: 1.17 to 1.45] and HRmen : 1.70 [95% CI: 1.43 to 2.02]), were associated with a higher risk of incident osteoporosis in both sexes. Low grip strength was associated with a higher risk of incident osteoporosis in men (HR: 1.38 [95% CI: 1.15 to 1.65]), but not in women. No significant interaction between the exposures and incident osteoporosis by age groups were identified. CONCLUSIONS: Our findings demonstrated that pre-sarcopenic men and sarcopenic women had a higher risk of developing osteoporosis even after adjustment for a large range of potential confounders. Considering that sarcopenia could be prevented, health interventions to improve physical capability may delay or prevent the onset of osteoporosis.