Tag: pubmed

Eur J Neurosci. 2021 Mar 6. doi: 10.1111/ejn.15174. Online ahead of print.

ABSTRACT

Affective-motivational disturbances are highly inconsistent in animal pain models. The reproducibility of the open-field test in assessing anxiety, malaise, or disability remains controversial despite its popularity. While traumatic, persistent, or multi-regional pain models are commonly considered more effective in inducing negative affect or functional impairment, the early psychobehavioral changes before pain chronification are often underexplored. Here, we aimed to clarify the fundamental relationship between hypernociception and passive distress-like behavior using a model of transient inflammatory pain. To minimize latent confounders and increase data consistency, male C57BL/6N mice were habituated to the open-field arena 6 times before receiving the unilateral intraplantar injection of prostaglandin E2 (PGE2) or vehicle. Open-field (40-minute exploration) and nociceptive behavior were evaluated repeatedly along the course of hypernociception in both wild-type and transgenic mice with a known pronociceptive phenotype. To reduce subjectivity, multivariate open-field behavioral outcomes were analyzed by statistical modeling based on exploratory factor analyses, which yielded a 2-factor solution. Within 3 hours after PGE2 injection, mice developed significantly reduced center exploration (factor 1) and a marginally significant increase in their habituation tendency (factor 2), which were not apparent in vehicle-injected mice. The behavioral passivity generally improved as hypernociception subsided. Therefore, transient inflammatory irritation is sufficient to suppress mouse open-field exploratory activity. The apparent absence of late affective-motivational changes in some rodents with prolonged hypernociception may not imply a lack of preceding or underlying neuropsychological alterations. Procedural pain after invasive animal experiments, however small, should be assessed and adequately controlled as a potential research confounder.

PMID:33675141 | DOI:10.1111/ejn.15174

Pharm Stat. 2021 Mar 5. doi: 10.1002/pst.2109. Online ahead of print.

ABSTRACT

The purpose of assessing adverse events (AEs) in clinical studies is to evaluate what AE patterns are likely to occur during treatment. In contrast, it is difficult to specify which of these patterns occurs in each patient. To tackle this challenging issue, we constructed a new statistical model including nonnegative matrix factorization by incorporating background knowledge of AE-specific structures such as severity and drug mechanism of action. The model uses a meta-analysis framework for integrating data from multiple clinical studies because insufficient information is derived from a single trial. We demonstrated the proposed method by applying it to real data consisting of three Phase III studies, two mechanisms of action, five anticancer treatments, 3317 patients, 848 AE types, and 99,546 AEs. The extracted typical treatment-specific AE patterns coincided with medical knowledge. We also demonstrated patient-level safety profiles using the data of AEs that were observed by the end of the second cycle.

PMID:33675157 | DOI:10.1002/pst.2109

J Cachexia Sarcopenia Muscle. 2021 Mar 5. doi: 10.1002/jcsm.12693. Online ahead of print.

ABSTRACT

BACKGROUND: Muscle atrophy is a common pathology associated with disuse, such as prolonged bed rest or spaceflight, and is associated with detrimental health outcomes. There is emerging evidence that disuse atrophy may differentially affect males and females. Cellular mechanisms contributing to the development and progression of disuse remain elusive, particularly protein turnover cascades. The purpose of this study was to investigate the initial development and progression of disuse muscle atrophy in male and female mice using the well-established model of hindlimb unloading (HU).

METHODS: One hundred C57BL/6J mice (50 male and 50 female) were hindlimb suspended for 0 (control), 24, 48, 72, or 168 h to induce disuse atrophy (10 animals per group). At designated time points, animals were euthanized, and tissues (extensor digitorum longus, gastrocnemius, and soleus for mRNA analysis, gastrocnemius and extensor digitorum longus for protein synthesis rates, and tibialis anterior for histology) were collected for analysis of protein turnover mechanisms (protein anabolism and catabolism).

RESULTS: Both males and females lost ~30% of tibialis anterior cross-sectional area after 168 h of disuse. Males had no statistical difference in MHCIIB fibre area, whereas unloaded females had ~33% lower MHCIIB cross-sectional area by 168 h of unloading. Both males and females had lower fractional protein synthesis rates (FSRs) within 24-48 h of HU, and females appeared to have a greater reduction compared with males within 24 h of HU (~23% lower FSRs in males vs. 40% lower FSRs in females). Males and females exhibited differential patterns and responses in multiple markers of protein anabolism, catabolism, and myogenic capacity during the development and progression of disuse atrophy. Specifically, females had greater mRNA inductions of catabolic factors Ubc and Gadd45a (~4-fold greater content in females compared with ~2-fold greater content in males) and greater inductions of anabolic inhibitors Redd1 and Deptor with disuse across multiple muscle tissues exhibiting different fibre phenotypes.

CONCLUSIONS: These results suggest that the aetiology of disuse muscle atrophy is more complicated and nuanced than previously thought, with different responses based on muscle phenotypes and between males and females, with females having greater inductions of atrophic markers early in the development of disuse atrophy.

PMID:33675163 | DOI:10.1002/jcsm.12693

Exp Physiol. 2021 Mar 6. doi: 10.1113/EP089431. Online ahead of print.

ABSTRACT

NEW FINDINGS: What is the central question of this study? To explore the relationship between proteins in skeletal muscle and adipose tissue determined at rest and peak rates of fat oxidation in men and women. What is the main finding and its importance? Resting content of proteins in skeletal muscle involved in triglyceride hydrolysis and mitochondrial lipid transport are more strongly associated with peak fat oxidation rates than proteins related to lipid transport, or hydrolysis in adipose tissue. Whilst females display higher relative rates of fat oxidation than males, this was unexplained by the proteins measured in this study, suggesting other factors determine sex-differences in fat metabolism.

ABSTRACT: This study explored key proteins involved in fat metabolism that may associate with peak fat oxidation (PFO) and account for sexual dimorphism in exercise fuel metabolism. Thirty-six healthy adults [15 females; age 40 (11); V̇O₂ peak 42.5 (9.5) mL⋅kg BM^-1 ⋅min^-1 ; means±SD] completed two exercise tests to determine PFO via indirect calorimetry. Resting adipose tissue and/or skeletal muscle biopsies were obtained to determine the protein content of adipose tissue PLIN1, CGI-58, HSL, ATGL, ACSL1, CPT1b and oestrogen receptor α (ERα), and skeletal muscle FABPpm, ATGL, ACSL1, CTP1b and ERα. Moderate strength correlations were found between PFO (mg⋅kg FFM^-1 ⋅min^-1 ) and the protein content of ATGL [r_s = 0.41 (0.03-0.68), P<0.05] and CPT1b [r_s = 0.45 (0.09-0.71), P<0.05] in skeletal muscle. No other statistically significant bivariate correlations were consistently found. Females had a greater relative PFO compared to males: 7.1±1.9 vs 4.5±1.3 and 7.3±1.7 vs 4.8±1.2 mg⋅kg FFM^-1 ⋅min^-1 )] in the adipose tissue (n = 14) and skeletal muscle (n = 12) sub-groups, respectively (p<0.05). No statistically significant sex differences were found in the content of these proteins. The regulation of PFO may involve processes relating to intramyocellular triglyceride hydrolysis and mitochondrial fatty acid transport, and adipose tissue is likely to play a more minor role than muscle. Sex differences in fat metabolism are likely to be due to factors other than the resting content of proteins in skeletal muscle and adipose tissue relating to triglyceride hydrolysis and fatty acid transport. This article is protected by copyright. All rights reserved.

PMID:33675111 | DOI:10.1113/EP089431

J Clin Pharm Ther. 2021 Mar 6. doi: 10.1111/jcpt.13398. Online ahead of print.

ABSTRACT

WHAT IS KNOWN AND OBJECTIVE: One of the effective and consistent ways to achieve glycaemic control for patients with type 2 diabetes mellitus (T2DM) is once-daily basal insulin. But it is also associated with adverse outcomes such as hypoglycaemia. Dulaglutide, a novel long-acting GLP-1 receptor agonist, may be a more suitable therapy. The present meta-analysis aims to assess the efficacy and safety of once-weekly glucagon-like peptide-1 receptor agonist dulaglutide compared with insulin glargine for the treatment of T2DM.

METHODS: We searched PubMed, Embase and Cochrane Library from inception to December 2020. Randomized clinical trials comparing dulaglutide with insulin glargine in adults with T2DM were included. Revman5.2 software was used for meta-analysis.

RESULTS AND DISCUSSION: We included 5 studies with 3383 randomized participants. Compared with insulin glargine, dulaglutide 1.5 mg led to greater mean HbA1c reduction (MD = -0.33%, 95% CI = -0.52, -0.15) whereas dulaglutide 0.75 mg did not (MD = -0.21%, 95% CI = -0.43, 0.01). Body weight loss was seen with dulaglutide whereas weight gain was seen with insulin glargine. The risk of hypoglycaemia was lower in dulaglutide 0.75 mg and 1.5 mg groups than in insulin glargine group,whereas dulaglutide had a statistically higher gastrointestinal adverse events incidence than insulin glargine.

WHAT IS NEW AND CONCLUSIONS: Compared with insulin glargine, dulaglutide may serve as an effective alternative to provide improvement in glycaemic control with weight loss and less hypoglycaemia in patients with T2DM. It may be a more suitable therapy instead of basal insulin.

PMID:33675117 | DOI:10.1111/jcpt.13398

J Vet Intern Med. 2021 Mar 6. doi: 10.1111/jvim.16089. Online ahead of print.

ABSTRACT

BACKGROUND: Echocardiographic measurements play an important role in detecting cardiac enlargement and assessing cardiac function. In human cardiology, M-mode measurements have been widely replaced by volumetric measurements of the left ventricle (LV) using Simpson’s method of disc (SMOD). In veterinary cardiology, more large-scale studies are necessary to generate reference intervals (RIs) for SMOD LV volume measurements.

OBJECTIVE: To generate body size independent RIs for LV volume measurements in dogs.

ANIMALS: Healthy adult dogs (n = 1331) of variable size and somatotype.

METHODS: Prospective study. The SMOD was measured from the right parasternal long axis and the left apical 4-chamber view in clinically healthy dogs. The SMOD measurements were normalized to various allometric scales (kg, kg^2/3 , or kg^1/3 ). RIs for LV end-diastolic volume (LVEDV) and LV end-systolic volume (LVESV) using SMOD were estimated as prediction intervals of both a linear and an additive regression model. Additionally, after normalization to body weight, 95% RIs were determined using nonparametric methods with 2.5 and 97.5 percentiles serving as the lower and upper limits. Separate analyses were performed for 120 sighthound breeds and 1211 other breeds.

RESULTS: Echocardiographic LV volumes correlated best with weight in kilograms. The additive model proved to be more flexible and accurate than the other 2 methods to generate RIs. Separate RIs for sighthound and all other breeds are provided.

CONCLUSIONS AND CLINICAL IMPORTANCE: Body size and breed-independent RIs for LV volume measurements using SMOD were generated prospectively from a large and diverse population of dogs and are available for clinical use.

PMID:33675121 | DOI:10.1111/jvim.16089

J Am Geriatr Soc. 2021 Mar 5. doi: 10.1111/jgs.17088. Online ahead of print.

ABSTRACT

BACKGROUND: Community health centers (CHCs) are federally funded safety-net clinics that provide care to low income and medically underserved persons. The proportion of CHC patients aged ≥65 doubled in the last ten years, yet little is known about this population. We aim to describe the demographic and clinical characteristics of the older adult CHC population.

DESIGN: Cross sectional analysis.

SETTING: The nationally representative 2014 Health Center Patient Survey.

PARTICIPANTS: CHC patients ≥55 years.

MEASURES: We used descriptive statistics to characterize older adults across demographic and clinical variables. To determine differences by age, we stratified into three groups (55-64, 65-74, 75+ years). We used t-tests and chi-squared to calculate p values and survey weights to make national estimates.

RESULTS: We included 1875 older adults ≥55 years, representing over 4.2 million people. Older adults were mostly aged 55-64 (60%), female (51%), and white (60%). The majority (73%) had Medicare or Medicaid and 47% reported fair or poor health. Regardless of age, older adults had an average of three chronic conditions and 0.6 impairments in activities of daily living (ADL). Healthcare utilization was not significantly different across age groups with most taking ≥5 prescription medications (54%) and one in five reporting ≥2 emergency department visits or ≥1 hospitalization in the last year.

CONCLUSIONS: Adults 55-64 who attend CHCs have similar disease burden as adults ≥65. As the population of older adults who access CHCs grow, our findings highlight the opportunity to enhance focus on key principles of geriatric medicine, such as measurement of functional impairment for those who are <65 while also addressing underlying health disparities.

PMID:33675077 | DOI:10.1111/jgs.17088

Hepatology. 2021 Mar 5. doi: 10.1002/hep.31784. Online ahead of print.

ABSTRACT

we read with interest the paper by Wellhöner et al. (1) about the effect of eradication of hepatitis C virus (HCV) infection on the gut microbiota. The Authors report that sustained virological response (SVR) at 24/48 weeks after hepatitis C virus (HCV) treatment does not lead to statistically significant changes in the gut microbiota of cirrhotic patients, but only in those with chronic hepatitis. Unfortunately, the Authors do not state the number of these two subgroups.

PMID:33675101 | DOI:10.1002/hep.31784

Ambio. 2021 Mar 5. doi: 10.1007/s13280-021-01503-3. Online ahead of print.

ABSTRACT

Trends in aquatic food consumption were matched against farm production surveys within Hubei province and compared to official production data and statistics. Surveys showed that consumer tastes were changing to a much broader aquatic food menu as their spending power increased. Traditional aquaculture species were becoming less profitable due to reduced profit margins as input costs increased and consumption preferences changed. Consequently, many producers were diversifying their production to meet local demand. Some farmers were also de-intensifying by reducing commercial aquafeed inputs and reverting to more traditional methods of dyke-crop culture to optimise trade-offs between input costs and labour, and manage their risk more effectively. In addition, analysis of local data showed that wholesale changes were occurring to aquaculture production as environmental protection legislation took effect which reduced the growing area for carps considerably.

PMID:33675016 | DOI:10.1007/s13280-021-01503-3

Transfusion. 2021 Mar 5. doi: 10.1111/trf.16313. Online ahead of print.

ABSTRACT

BACKGROUND: Antigens from the Rh and Kell systems are recognized as the most immunogenic in clinical practice. This study evaluated the possible molecular mechanisms involved in the interaction of antigenic peptides with the DRB1 molecules, which help to explain the high frequency of anti-K and association of D + C antibodies in transfusion and incompatible pregnancy.

STUDY DESIGN AND METHODS: We included 201 patients with antibodies against antigens from the Rh and Kell systems and compare them with 174,015 controls. HLA-DRB1 genotyping and in silico analysis were performed. The NetMHCIIpan software was used to identify RhD-, RhCE-, and KEL-derived anchor peptides that bind to DRB1 molecules.

RESULTS: HLA-DRB1*15 is associated with an increased risk of D, C, E, and K alloimmunization, while the HLA-DRB1*01 and *12 alleles are overrepresented in patients with anti-C and anti-D, respectively. In silico analysis showed that three polymorphic points (60I, 68S, and 103S) common to C and D antigens can be presented by several DRB1 molecules, including DRB1*15:01. The DRB1*09:01 molecule, although not showing statistical significance, was able to interact strongly with almost all five anchor peptides from the sequence containing the polymorphic determinants of E antigen, except 217-WMFWPSVNS-225.

CONCLUSION: The DRB1*15 molecule has specific physicochemical characteristics in residues 11P and 13R in the P4 pocket that can favor the response to various antigenic peptides. Anti-K alloimmunization is unrestricted for interaction with specific DRB1 molecules, which suggests that almost all individuals in our population have DRB1 molecules capable of binding to KEL-derived anchor peptides and produce anti-K when stimulated.

PMID:33675036 | DOI:10.1111/trf.16313