Age and dietary restriction modulate mitochondrial quality in quadriceps femoris muscle of male mice.

Dietary restriction (DR) is a potential intervention for ameliorating ageing-related damages. Mitochondrial quality control is the key mechanism for regulating cellular functions in skeletal muscle. This study aimed to explore the effect of age and DR on the homeostasis of mitochondrial quality control in skeletal muscle. To study the effect of age on mitochondrial homeostasis, young (3 months old) male C57BL/6J mice were fed ad libitum (AL) until 7 (Young), 14 (Middle), and 19 months (Aged) of age. For the DR intervention, 60% of AL intake was given to the mice at 3 months of age until they reached 19 months of age (16 months). The quadriceps femoris muscle was collected for further analysis. Significant changes in the skeletal muscle were noticed during the transition between middle age and the elderly stages. An accumulation of collagen was observed in the muscle after middle age. Compared with the Middle muscle, Aged muscle displayed a greater expression of VDAC, and lower expressions of mitochondrial dynamic proteins and OXPHOS proteins. The DR intervention attenuated collagen content and elongated the sarcomere length in the skeletal muscle during ageing. In addition, DR adjusted the abnormalities in mitochondrial morphology in the Aged muscle. DR downregulated VDAC expression, but upregulated OPA1 and DRP1 expressions. Taken together, greater pathological changes were noticed in the skeletal muscle during ageing, especially in the transition between middle age and the elderly, whereas early-onset DR attenuated the muscular ageing via normalising partial functions of mitochondria.

Weight regain, but not weight loss exacerbates hepatic fibrosis during multiple weight cycling events in male mice.

PURPOSE: Weight cycling is a phenomenon characterized by fluctuating body weight that is commonly observed in individuals employing intentional weight loss methods. Despite its prevalence, the impact of weight cycling on health remains equivocal. The current investigation aimed to examine the effects of weight cycling on liver health. METHODS: The weight cycling model was established by switching the feeding method of mice between ad libitum (AL) and restricted intake (DR or 60% of AL) of the breeding diet to cause weight gain and weight loss, respectively. The weight cycling model comprised two and a half cycles, with one group terminating the experience during the weight-gain period (S-AL) and the other during the weight-loss period (S-DR). Liver tissue was collected to investigate morphology alterations, apoptosis, lipid metabolism, and mitochondrial homeostasis. RESULTS: The results demonstrated that the termination point of weight cycling affected body weight and hepatic steatosis. All parameters examined in the S-DR mice exhibited a comparable trend to those observed in the DR mice. Notably, S-AL mice showed a significant increase in lipid metabolism-related proteins in the liver compared to AL-fed mice, along with reduced lipid droplets. Moreover, hepatic apoptosis and fibrosis were exacerbated in the S-AL mice compared to AL mice, whereas mitochondrial fusion, biogenesis, and mitophagy were decreased in the S-AL mice. CONCLUSION: Weight cycling ending in weight gain exacerbated hepatic fibrosis, potentially by inducing apoptosis or disrupting mitochondrial homeostasis. Conversely, weight cycling ending in weight loss demonstrated beneficial effects on hepatic health.

Estimating genetic parameters of digital behavior traits and their relationship with production traits in purebred pigs.

BACKGROUND: With the introduction of digital phenotyping and high-throughput data, traits that were previously difficult or impossible to measure directly have become easily accessible, offering the opportunity to enhance the efficiency and rate of genetic gain in animal production. It is of interest to assess how behavioral traits are indirectly related to the production traits during the performance testing period. The aim of this study was to assess the quality of behavior data extracted from day-wise video recordings and estimate the genetic parameters of behavior traits and their phenotypic and genetic correlations with production traits in pigs. Behavior was recorded for 70 days after on-test at about 10 weeks of age and ended at off-test for 2008 female purebred pigs, totaling 119,812 day-wise records. Behavior traits included time spent eating, drinking, laterally lying, sternally lying, sitting, standing, and meters of distance traveled. A quality control procedure was created for algorithm training and adjustment, standardizing recording hours, removing culled animals, and filtering unrealistic records. RESULTS: Production traits included average daily gain (ADG), back fat thickness (BF), and loin depth (LD). Single-trait linear models were used to estimate heritabilities of the behavior traits and two-trait linear models were used to estimate genetic correlations between behavior and production traits. The results indicated that all behavior traits are heritable, with heritability estimates ranging from 0.19 to 0.57, and showed low-to-moderate phenotypic and genetic correlations with production traits. Two-trait linear models were also used to compare traits at different intervals of the recording period. To analyze the redundancies in behavior data during the recording period, the averages of various recording time intervals for the behavior and production traits were compared. Overall, the average of the 55- to 68-day recording interval had the strongest phenotypic and genetic correlation estimates with the production traits. CONCLUSIONS: Digital phenotyping is a new and low-cost method to record behavior phenotypes, but thorough data cleaning procedures are needed. Evaluating behavioral traits at different time intervals offers a deeper insight into their changes throughout the growth periods and their relationship with production traits, which may be recorded at a less frequent basis.

Pigs lacking the SRCR5 domain of CD163 protein demonstrate heritable resistance to the PRRS virus and no changes in animal performance from birth to maturity.

Porcine reproductive and respiratory syndrome (PRRS) is one of the world's most persistent viral pig diseases, with a significant economic impact on the pig industry. PRRS affects pigs of all ages, causing late-term abortions and stillbirths in sows, respiratory disease in piglets, and increased susceptibility to secondary bacterial infection with a high mortality rate. PRRS disease is caused by a positive single-stranded RNA PRRS virus (PRRSV), which has a narrow host-cell tropism limited to monocyte-macrophage lineage cells. Several studies demonstrated that the removal of CD163 protein or, as a minimum, its scavenger receptor cysteine-rich domain 5 (SRCR5) precludes the viral genome release, conferring resistance to PRRSV in live animals. Today, very limited information exists about the impact of such edits on animal performance from birth to maturity in pigs. Using CRISPR-Cas9 with dual-guide RNAs and non-homologous end joining (NHEJ), first-generation (E0) pigs were produced with a deletion of exon 7 in the CD163 gene. The selected pigs were bred to produce the next three generations of pigs to establish multiple lines of pigs homozygous for the edited allele, thereby confirming that the CD163 gene with removed exon 7 was stable during multiple breeding cycles. The pigs were evaluated relative to non-edited pigs from birth to maturity, including any potential changes in meat composition and resistance to PRRSV. This study demonstrates that removing the SRCR5 domain from the CD163 protein confers resistance to PRRSV and, relative to unedited pigs, resulted in no detected differences in meat composition and no changes in the growth rate, health, and ability to farrow. Together, these results support the targeted use of gene editing in livestock animals to address significant diseases without adversely impacting the health and well-being of the animals or the food products derived from them.

The influence of prior use of inhaled corticosteroids on COVID-19 outcomes: A systematic review and meta-analysis.

The influence of inhaled corticosteroids (ICS) on COVID-19 outcomes remains uncertain. To address this, we conducted a systematic review and meta-analysis, analyzing 30 studies, to investigate the impact of ICS on patients with COVID-19. Our study focused on various outcomes, including mortality risk, hospitalization, admission to the intensive care unit (ICU), mechanical ventilation (MV) utilization, and length of hospital stay. Additionally, we conducted a subgroup analysis to assess the effect of ICS on patients with chronic obstructive pulmonary disease (COPD) and asthma. Our findings suggest that the prior use of ICS did not lead to significant differences in mortality risk, ICU admission, hospitalization, or MV utilization between individuals who had used ICS previously and those who had not. However, in the subgroup analysis of patients with COPD, prior ICS use was associated with a lower risk of mortality compared to non-users (OR, 0.95; 95% CI, 0.90-1.00). Overall, while the use of ICS did not significantly affect COVID-19 outcomes in general, it may have beneficial effects specifically for patients with COPD. Nevertheless, more research is needed to establish a definitive conclusion on the role of ICS in COVID-19 treatment. PROSPERO registration number: CRD42021279429.

Early Identification of Sepsis-Induced Acute Kidney Injury by Using Monocyte Distribution Width, Red-Blood-Cell Distribution, and Neutrophil-to-Lymphocyte Ratio.

Sepsis-induced acute kidney injury (AKI) is a common complication in patients with severe illness and leads to increased risks of mortality and chronic kidney disease. We investigated the association between monocyte distribution width (MDW), red-blood-cell volume distribution width (RDW), neutrophil-to-lymphocyte ratio (NLR), sepsis-related organ-failure assessment (SOFA) score, mean arterial pressure (MAP), and other risk factors and sepsis-induced AKI in patients presenting to the emergency department (ED). This retrospective study, spanning 1 January 2020, to 30 November 2020, was conducted at a university-affiliated teaching hospital. Patients meeting the Sepsis-2 consensus criteria upon presentation to our ED were categorized into sepsis-induced AKI and non-AKI groups. Clinical parameters (i.e., initial SOFA score and MAP) and laboratory markers (i.e., MDW, RDW, and NLR) were measured upon ED admission. A logistic regression model was developed, with sepsis-induced AKI as the dependent variable and laboratory parameters as independent variables. Three multivariable logistic regression models were constructed. In Model 1, MDW, initial SOFA score, and MAP exhibited significant associations with sepsis-induced AKI (area under the curve [AUC]: 0.728, 95% confidence interval [CI]: 0.668-0.789). In Model 2, RDW, initial SOFA score, and MAP were significantly correlated with sepsis-induced AKI (AUC: 0.712, 95% CI: 0.651-0.774). In Model 3, NLR, initial SOFA score, and MAP were significantly correlated with sepsis-induced AKI (AUC: 0.719, 95% CI: 0.658-0.780). Our novel models, integrating MDW, RDW, and NLR with initial SOFA score and MAP, can assist with the identification of sepsis-induced AKI among patients with sepsis presenting to the ED.

Genetic parameters for pelvic organ prolapse in purebred and crossbred sows.

This study aimed to investigate genetic parameters for sow pelvic organ prolapse in purebred and crossbred herds. Pelvic organ prolapse was recorded as normal or prolapsed on the individual sow level across 32 purebred and 8 crossbred farms. In total, 75,162 purebred Landrace sows from a single maternal line were recorded between 2018 and 2023, while 18,988 commercial two-way crossbred (Landrace x Large White) sows were available between 2020 and 2023. There were 5,122,005 animals included in the pedigree. The prolapse in purebreds and crossbreds was considered two different traits in the model. Pedigrees of the crossbred sows were determined based on genotypes through parentage assignment. The average incidence rates were 1.81% and 3.93% for purebreds and crossbreds, respectively. The bivariate model incorporated fixed effects of parity group and region with random effects of contemporary group (farm and mating year and month at the first parity), additive genetic, and residual. Genetic parameter estimates were obtained using BLUPF90+ with the AIREML option. The estimated additive variance was larger in crossbreds than in purebreds. Estimates of heritability in the observed scale were 0.09 (0.006) for purebreds and 0.11 (0.014) for crossbreds, with a genetic correlation of 0.83 using a linear model. Results suggested that including data from crossbreds with higher incidence rate is beneficial and selection to reduce the prolapse incidence in purebred sow herds would also benefit commercial crossbred sow herds.

Cooperation between PRMT1 and PRMT6 drives lung cancer health disparities among Black/African American men.

Lung cancer is the third most common cancer with Black/AA men showing higher risk and poorer outcomes than NHW men. Lung cancer disparities are multifactorial, driven by tobacco exposure, inequities in care access, upstream health determinants, and molecular determinants including biological and genetic factors. Elevated expressions of protein arginine methyltransferases (PRMTs) correlating with poorer prognosis have been observed in many cancers. Most importantly, our study shows that PRMT6 displays higher expression in lung cancer tissues of Black/AA men compared to NHW men. In this study, we investigated the underlying mechanism of PRMT6 and its cooperation with PRMT1 to form a heteromer as a driver of lung cancer. Disrupting PRMT1/PRMT6 heteromer by a competitive peptide reduced proliferation in non-small cell lung cancer cell lines and patient-derived organoids, therefore, giving rise to a more strategic approach in the treatment of Black/AA men with lung cancer and to eliminate cancer health disparities.

Correlating Reiff scores with clinical, functional, and prognostic factors: characterizing noncystic fibrosis bronchiectasis severity: validation from a nationwide multicenter study in Taiwan.

BACKGROUND: Our study aimed to confirm a simplified radiological scoring system, derived from a modified Reiff score, to evaluate its relationship with clinical symptoms and predictive outcomes in Taiwanese patients with noncystic fibrosis bronchiectasis (NCFB). METHODS: This extensive multicenter retrospective study, performed in Taiwan, concentrated on patients diagnosed with NCFB verified through high-resolution computed tomography (HRCT) scans. We not only compared the clinical features of various types of bronchiectasis (cylindrical, varicose, and cystic). Furthermore, we established relationships between the severity of clinical factors, including symptom scores, pulmonary function, pseudomonas aeruginosa colonization, exacerbation and admission rates, and HRCT parameters using modified Reiff scores. RESULTS: Data from 2,753 patients were classified based on HRCT patterns (cylindrical, varicose, and cystic) and severity, assessed by modified Reiff scores (mild, moderate, and severe). With increasing HRCT severity, a significant correlation was found with decreased forced expiratory volume in the first second (FEV1) (p < 0.001), heightened clinical symptoms (p < 0.001), elevated pathogen colonization (pseudomonas aeruginosa) (p < 0.001), and an increased annual hospitalization rate (p < 0.001). In the following multivariate analysis, elderly age, pseudomonas aeruginosa pneumonia, and hospitalizations per year emerged as the only independent predictors of mortality. CONCLUSION: Based on our large cohort study, the simplified CT scoring system (Reiff score) can serve as a useful adjunct to clinical factors in predicting disease severity and prognosis among Taiwanese patients with NCFB.

Clinical Predictors of Nontuberculous Mycobacteria Lung Disease and Coisolates of Potential Pathogenic Microorganisms in Noncystic Fibrosis Bronchiectasis.

Background: In bronchiectasis, nontuberculous mycobacteria (NTM) lung disease (NTM-LD) is a well-known coexisting infection. However, microorganism coisolates and clinical NTM-LD predictors are poorly studied. Methods: Patients with bronchiectasis diagnosed by means of computed tomography between January 2017 and June 2020 were screened, using the date of computed tomography as the index date. Those with a major bronchiectasis diagnosis in ≥2 follow-up visits after the index date were enrolled in the study, and NTM-LD occurrence and its association with pneumonia and hospitalization within 1 year were analyzed. Results: Of the 2717 participants, 79 (2.9%) had NTM-LD diagnosed. The factors associated with NTM-LD included hemoptysis, postinfectious bronchiectasis, a tree-in-bud score ≥2, a modified Reiff score ≥4, and chronic obstructive pulmonary disease (adjusted odds ratios, 1.80, 2.36, 1.78, 2.95, and 0.51, respectively). Compared with patients in the non-NTM group, those with NTM-LD had higher rates of hospitalization (15.9% vs 32.9%; P < .001) and pneumonia (9.8% vs 20.3%; P = .003). Pseudomonas aeruginosa was the most common microorganism in those with NTM-LD and those in the non-NTM group (10.1% vs 7.8%; P = .40). However, compared with those in the non-NTM group, Acinetobacter baumannii and Escherichia coli were more prevalent in patients with NTM-LD (0.7% vs 3.8% [P = .03%] and 1.0% vs 3.8% [P = .05], respectively). Conclusions: Postinfectious bronchiectasis with hemoptysis, higher radiological involvement, and a tree-in-bud pattern were associated with NTM-LD risk. The rate of A baumannii and E coli coisolation was higher in bronchiectasis populations with NTM-LD.