Sex differences in clinical characteristics and their influence on clinical outcomes in an observational cohort of patients with rheumatoid arthritis

ObjectiveRheumatoid arthritis (RA) is more prevalent in women, but sex differences remain incompletely understood. This study aimed to elucidate sex differences in clinical characteristics and their potential impact on clinical outcomes in a large Korean cohort of patients with RA.MethodsIn total, 5376 RA patients from the KORean Observational study Network for Arthritis (KORONA) database were examined at baseline and for 3 consecutive years using the disease activity score 28 (DAS28), health assessment questionnaire (HAQ), and patient-reported outcomes (PROs). Within a subgroup with active disease (DAS28 ≥ 3.2) at baseline, sex impacts on clinical outcome during follow-up were analyzed using generalized estimating equation (GEE) models. The factors related to achieving clinical remission were analyzed using Cox-proportional hazard regression.ResultsAt baseline, women (n = 4574) were younger and had more erosive disease and longer disease duration than men (n = 802) with higher scores in DAS28, HAQ, and PROs. The prevalence of interstitial lung disease, cardiovascular disease, and diabetes in men was higher than that of women. In a RA subgroup with active disease at baseline, GEE analyses demonstrated that women RA significantly influenced the rate of change of DAS28 over time. In that group, men are associated with achieving DAS28 sustained remission and point remission.ConclusionsWomen with RA in Korea report higher levels of disease activity and PROs compared to men, whereas most comorbidities were more prevalent in men. The longitudinal change in disease activity and the rate of achieving clinical remission were found to be worse in women with RA.     

“It’s a tool,not a cure”: the preoperative teen perspective on bariatric surgery

BackgroundBariatric surgery is well established in adults as the most effective tool for sustained weight loss and reduction of obesity-related co-morbidities, and is an emerging option for adolescents in whom conservative approaches have failed. Narratives are vital in understanding the motivating reasons and psychosocial profiles of adolescents considering bariatric surgery during a developmental period of evolving self-concept, body image sensitivity, peer pressure, and increased opportunity for risky behaviors.ObjectivesTo explore preoperative adolescent patient perspectives on their decision to pursue bariatric surgery, anticipated physical and psychosocial effects, and preparation process.SettingsThe Hospital for Sick Children (SickKids) in Toronto, Ontario, Canada.MethodsWe conducted 14 semi-structured interviews with adolescents (16–18 yr old) 2–4 months before bariatric surgery. A theoretical thematic analysis was conducted with 3 independent reviewers (interrater reliability, Cronbach’s α= .81) and conflicts were resolved through discussion.ResultsPatients’ perspectives are captured in 4 themes: motivation for surgery, effects on health and habits, psychosocial changes, and support systems during preparation. Participants perceived surgery as a tool but not a solution for weight loss. Most were motivated for health and daily functional improvement rather than aesthetic reasons, and some anticipated improved social interactions while maintaining their self-identity. Participants were selective in sharing news of their surgery, and received varying levels of support from families, friends, and healthcare teams.ConclusionAdolescents seem generally prepared for and informed about surgery, with expectations for weight loss and psychosocial improvements, although uncertainty and contradictory thoughts were prevalent. Insights provided by these adolescent patients will help optimize bariatric surgery assessments and support from clinical teams and inform preoperative education for future patients and families.     

Mechanisms linking gut microbial metabolites to insulin resistance

Insulin resistance is the rate-limiting step in the development of metabolic diseases, including type 2 diabetes. The gut microbiota has been implicated in host energy metabolism and metabolic diseases and is recognized as a quantitatively important organelle in host metabolism, as the human gut harbors 10 trillion bacterial cells. Gut microbiota break down various nutrients and produce metabolites that play fundamental roles in host metabolism and aid in the identification of possible therapeutic targets for metabolic diseases. Therefore, understanding the various effects of bacterial metabolites in the development of insulin resistance is critical. Here, we review the mechanisms linking gut microbial metabolites to insulin resistance in various insulin-responsive tissues.     

Immunogenicity,safety and reactogenicity of ROTAVAC® in healthy infants aged 6–8 weeks in Vietnam

BackgroundROTAVAC® is derived from human 116E rotavirus (RV) neonatal strain. In this study, we evaluated the immunogenicity, safety and reactogenicity of ROTAVAC® in Vietnam.MethodWe conducted a phase IV clinical trial in healthy infants aged 6–8 weeks using the complete regimen of ROTAVAC® with three doses. Serum anti-RV IgA was measured by enzyme-linked immunosorbent assay to assess the geometric mean concentration in infants who received the complete regimen of the vaccine.ResultsA total of 360 participants were enrolled in this clinical trial. The mean age ± standard deviation at enrollment was 6.9 ± 0.6 weeks. The anti-RV IgA titer was 4.01 ± 3.74 mg/ml pre-vaccination and substantially increased to 29.27 ± 80.64 mg/ml post-vaccination. The value of logIgA significantly increased (p = 0.003) from 0.28 ± 0.79 to 1.03 ± 0.54. The proportion of participants with equal to and greater than 3-fold and 4-fold shifts in pre- to post-vaccination antibody titer (IgA) were 55.4% and 48.3%, respectively. No adverse events or serious adverse events were recorded immediately within 30 min after the administration of each dose. The most common adverse events within 14 days after each visit were fever, unusual crying and irritability. Other adverse events occurred at a low rate, and no case of intussusception was noted.ConclusionsThe complete regimen of ROTAVAC® demonstrated an immunological response with clinically acceptable safety profile. Post-completion of this study, ROTAVAC® is now a WHO-prequalified vaccine and available in Vietnam.     

Akt/PKB activation in gastric carcinomas correlates with clinicopathologic variables and prognosis

Akt/protein kinase B (PKB) plays an important role in cell survival. However, the role of Akt in the biology of gastric cancer has not been well studied. We sought to investigate the expression of Akt or phosphorylated Akt (pAkt) in human gastric carcinomas and to analyze the relationship between Akt or pAkt and the clinicopathologic parameters. The expressions of Akt and pAkt were evaluated immunohistochemically in 311 gastric carcinomas using the tissue array method. Akt expression was detected in 74% of the tumors and pAkt expression in 78%. pAkt was highly expressed in the early stage of pTNM (p=0.011). We also found an inverse association between pAkt and lymphatic invasion (p=0.01) or lymph node metastasis (p=0.008). pAkt expression was significantly correlated with a higher survival in patients with stage I carcinomas (p=0.0003). Interestingly, combined evaluation revealed that the group with pAkt-positive and lymph node-negative carcinomas showed a better prognosis than the other groups (p<0.0001). In addition, pAkt was shown to correlate positively with APC (p=0.002) and Smad4 (p<0.0001) expression. These findings suggest that pAkt expression may help to predict the clinical outcome of gastric cancer patients.     

Changes of nitric oxide synthase activity and free methylarginines contents in regenerating rat liver after partial hepatectomy

In the present study, liver regeneration rate (%) was increased up to 70% 3 days after partial hepatectomy (PH). Nitric oxide synthase (NOS) activity in liver tissue as well as serum nitrite/nitrate content had no timed response, revealing no significant difference between shamoperated and partially hepatectomized rat liver. Contents of free methylarginines in liver tissue were increased biphasically in a time-dependent manner after PH. However, those in serum did not exhibit the same patterns as in liver. Taken together, the results suggest that N^G-monomethyl-L-arginine (MMA) and N^G, N^G-dimethylarginine (DMA) play a role in inhibiting nitric oxide (NO) synthesis in regenerating rat liver because the increase of their contents was synchronized with NOS expression.     

Inhibitory effects of plant extracts on adjuvant-induced arthritis

Twenty seven plant extracts were selected on the basis of ancient literature search for rheumatoid arthritis or similar syndrome. Methanol extract of each plant was prepared and administered orally to rats everyday at a dose of 200 mg/kg/day. Experimental arthritis was induced by subplantar injection of heat-killedMycobacterium butyricum to right hind paw of rats. This treatment provoked swelling of the treated paw in two phases, acute primary swelling and secondary arthritic swelling. An inhibition of secondary swelling was considered to be antiarthritic activity. Several plant methanol extracts such asAkebia quinata (caulis),Ephedra sinica (herba) andSophorae subprostrata (radix) were found to show significant inhibitory activity against secondary swelling at the dose tested. Our results strongly suggested an antiarthritic potential of these plant extracts.     

An improved synthesis of methyl p-hydroxyphenylalkanoates

Friedel-Crafts reaction of isopropoxybenzene with methyl α-chloro-α-(methylthio)acetate1 afforded methyl α-methylthio-p-isopropoxyphenylacetate2d, which was readily converted into methyl p-isopropoxyphenylacetate3 by reductive desulfurization with zinc dust in acetic acid. Methylation of3 with sodium hydride and methyl iodide gave methyl α-(p-isopropoxyphenyl)propionate5. Methyl p-hydroxyphenylalkanoates (4, 6), useful intermediates for some medicines, were easily prepared by treatment of3 and5 with titanium tetrachloride, respectively.     

Hydrolysis kinetics of metampicillin by high performance liquid chromatography

The hydrolysis of metampicillin to ampicillin was investigated using high performance liquid chromatography. We developed the simultaneous determination of metampicillin and ampicillin using a Zorbax CN column and 5% acetonitrile and 8% methanol in 0.02 M phosphate buffer (pH 7.0) as mobile phase. Metampicillin was hydrolyzed to ampicillin with half life of 41.5 min at physiological pH and temperature. In acidic pH, metampicillin was rapidly hydrolyzed to ampicillin within a chromatographic separation.