Context and Objective: Obesity is associated with activation of the TNF-α system, increased inflammatory markers, and insulin resistance. Although studies in rodents suggest that attenuation of TNF ...activity improves glucose homeostasis, the effect of prolonged inhibition of TNF-α with etanercept on inflammation and glucose homeostasis in a human model of obesity is not known.
Design and Participants: Forty obese subjects with features of metabolic syndrome were randomized to etanercept or placebo, 50 mg twice weekly for 3 months, followed by 50 mg once weekly for 3 months.
Outcome Measures: Subjects underwent oral glucose tolerance testing and measurement of serum inflammatory biomarkers and adipokines. Subcutaneous fat biopsy was performed in a subset for measurement of adipokine and TNF-α mRNA expression.
Results: Visceral adiposity was significantly associated with serum concentrations of TNF receptor 1 (TNFR1), TNFR2, and vascular cell adhesion molecule-1 and adipose tissue expression of TNF-α and SOCS-3 (all P < 0.05). Insulin resistance as assessed by homeostasis model assessment was significantly associated with TNFR1, C-reactive protein, IL-6, and soluble intracellular adhesion molecule-1 (sICAM-1) (all P < 0.05). Etanercept significantly improved fasting glucose (treatment effect vs. placebo over 6 months, −10.8 ± 4.4%, P = 0.02). Etanercept also increased the ratio of high molecular weight adiponectin to total adiponectin (+22.1 ± 9.2% vs. placebo, P = 0.02), and decreased levels of sICAM-1 (−11 ± 2% vs. placebo, P < 0.0001). In contrast, body composition, lipids, C-reactive protein, and IL-6 were unchanged after 6 months.
Conclusions: Prolonged therapy with etanercept improved fasting glucose, increased the ratio of high molecular weight to total adiponectin, and decreased sICAM-1 in obese subjects with abnormal glucose homeostasis and significant subclinical inflammation.
Etanercept treatment decreases fasting glucose and increases the ratio of HMW:total adiponectin in obesity, without any effect on body composition or lipids.
Tuberculosis causes significant morbidity and mortality worldwide, especially in sub-Saharan Africa. DC-SIGN, encoded by CD209, is a receptor capable of binding and internalizing Mycobacterium ...tuberculosis. Previous studies have reported that the CD209 promoter single nucleotide polymorphism (SNP)-336A/G exerts an effect on CD209 expression and is associated with human susceptibility to dengue, HIV-1 and tuberculosis in humans. The present study investigates the role of the CD209 -336A/G variant in susceptibility to tuberculosis in a large sample of individuals from sub-Saharan Africa.
A total of 2,176 individuals enrolled in tuberculosis case-control studies from four sub-Saharan Africa countries were genotyped for the CD209 -336A/G SNP (rs4804803). Significant overall protection against pulmonary tuberculosis was observed with the -336G allele when the study groups were combined (n = 914 controls vs. 1262 cases, Mantel-Haenszel 2 x 2 chi(2) = 7.47, P = 0.006, odds ratio = 0.86, 95%CI 0.77-0.96). In addition, the patients with -336GG were associated with a decreased risk of cavitory tuberculosis, a severe form of tuberculosis disease (n = 557, Pearson's 2x2 chi(2) = 17.34, P = 0.00003, odds ratio = 0.42, 95%CI 0.27-0.65). This direction of association is opposite to a previously observed result in a smaller study of susceptibility to tuberculosis in a South African Coloured population, but entirely in keeping with the previously observed protective effect of the -336G allele.
This study finds that the CD209 -336G variant allele is associated with significant protection against tuberculosis in individuals from sub-Saharan Africa and, furthermore, cases with -336GG were significantly less likely to develop tuberculosis-induced lung cavitation. Previous in vitro work demonstrated that the promoter variant -336G allele causes down-regulation of CD209 mRNA expression. Our present work suggests that decreased levels of the DC-SIGN receptor may therefore be protective against both clinical tuberculosis in general and cavitory tuberculosis disease in particular. This is consistent with evidence that Mycobacteria can utilize DC-SIGN binding to suppress the protective pro-inflammatory immune response.
To protect the ceria electrolyte from reduction at the anode side, a thin film of yttria-stabilized zirconia (YSZ) is introduced as an electronic blocking layer to anode-supported gadolinia-doped ...ceria (GDC) electrolyte solid oxide fuel cells (SOFCs). Thin films of YSZ/GDC bilayer electrolyte are deposited onto anode substrates using a simple and cost-effective wet ceramic co-sintering process. A single cell, consisting of a YSZ (∼3
μm)/GDC (∼7
μm) bilayer electrolyte, a La
0.8Sr
0.2Co
0.2Fe
0.8O
3–GDC composite cathode and a Ni–YSZ cermet anode is tested in humidified hydrogen and air. The cell exhibited an open-circuit voltage (OCV) of 1.05
V at 800
°C, compared with 0.59
V for a single cell with a 10-μm GDC film but without a YSZ film. This indicates that the electronic conduction through the GDC electrolyte is successfully blocked by the deposited YSZ film. In spite of the desirable OCVs, the present YSZ/GDC bilayer electrolyte cell achieved a relatively low peak power density of 678
mW
cm
−2 at 800
°C. This is attributed to severe mass transport limitations in the thick and low-porosity anode substrate at high current densities.
By 2050, it is predicted that six million hip fractures will occur each year of which the majority will happen in Asia. Malaysia is not spared from this predicted rise and its rate of increase will ...be one of the highest in this region. Much of this is driven by our unprecedented growth in the number of older people. Characteristics of individuals with hip fractures in Malaysia mirror what has been reported in other countries. They will be older multimorbid people who were already at risk of falls and fractures. Outcomes were poor with at least a quarter do not survive beyond 12 months and in those that do survive have limitation in their mobility and activities of daily living. Reviewing how these fractures are managed and incorporating new models of care, such as orthogeriatric care, could address these poor outcomes. Experts have warned of the devastating impact of hip fracture in Malaysia and that prompt action is urgently required. Despite that, there remains no national agenda to highlight the need to improve musculoskeletal health in the country.
Keratoconus (KC) is an ectatic corneal disease characterized by progressive thinning and irregular astigmatism, and a leading indication for corneal transplantation. KC-associated changes have been ...demonstrated for the entire cornea, but the pathological thinning and mechanical weakening is usually localized. We performed quantitative proteomics using Sequential Windowed Acquisition of All Theoretical Fragment Ion Mass Spectrometry (SWATH-MS) to analyze epithelial and stromal changes between the topographically-abnormal cone and topographically-normal non-cone regions of advanced KC corneas, compared to age-matched normal corneas. Expression of 20 epithelial and 14 stromal proteins was significantly altered (≥2 or ≤0.5-fold) between cone and non-cone in all 4 KC samples. Ingenuity pathway analysis illustrated developmental and metabolic disorders for the altered epithelial proteome with mitochondrion as the significant gene ontology (GO) term. The differential stromal proteome was related to cellular assembly, tissue organization and connective tissue disorders with endoplasmic reticulum protein folding as the significant GO term. Validation of selected protein expression was performed on archived KC, non-KC and normal corneal specimens by immunohistochemistry. This is the first time to show that KC-associated proteome changes were not limited to the topographically-thinner and mechanically-weakened cone but also non-cone region with normal topography, indicating a peripheral involvement in KC development.
To determine susceptibility genes for high myopia in Singaporean Chinese.
A meta-analysis of 2 genome-wide association (GWA) datasets in Chinese and a follow-up replication cohort in Japanese.
Two ...independent datasets of Singaporean Chinese individuals aged 10 to 12 years (Singapore Cohort Study of the Risk factors for Myopia SCORM: cases = 65, controls = 238) and more than 21 years (Singapore Prospective Study Program SP2: cases = 222, controls = 435) for GWA studies, and a Japanese dataset aged more than 20 years (cases = 959, controls = 2128) for replication.
Genomic DNA samples from SCORM and SP2 were genotyped using various Illumina Beadarray platforms (>HumanHap 500). Single-locus association tests were conducted for each dataset with meta-analysis using pooled z-scores. The top-ranked genetic markers were examined for replication in the Japanese dataset. Fisher P was calculated for the combined analysis of all 3 cohorts.
High myopia, defined by spherical equivalent (SE) ≤ -6.00 diopters (D); controls defined by SE between -0.50 and +1.00 D.
Two SNPs (rs12716080 and rs6885224) in the gene CTNND2 on chromosome 5p15 ranked top in the meta-analysis of our Chinese datasets (meta P = 1.14 × 10(-5) and meta P = 1.51 × 10(-5), respectively) with strong supporting evidence in each individual dataset analysis (max P = 1.85 × 10(-4) in SCORM: max P = 8.8 × 10(-3) in SP2). Evidence of replication was observed in the Japanese dataset for rs6885224 (P = 0.035, meta P of 3 datasets: 7.84 × 10(-6)).
This study identified a strong association of CTNND2 for high myopia in Asian datasets. The CTNND2 gene maps to a known high myopia linkage region on chromosome 5p15.
Nanoparticles appear to be one of the most promising agents that offer efficacy in angiogenesis-related disease therapy. The objective of this research is to systematically review studies that have ...probed into the effect of nanoparticles on angiogenesis. Selected inclusion criteria were used to extract articles, references that were cited in the initial search were sought to identify more potential articles, and articles that did not meet the inclusion criteria and duplicates were discarded. The spherical shape was shown to be the most common shape employed to investigate the role of nanoparticles in angiogenesis therapy. The size of nanoparticles appears to play a crucial role for efficacy on angiogenesis, in which 20 nm emerged as the preferred size. Gold nanoparticles exhibit the most promise as an antiangiogenesis agent, and the toxicity was adjustable based on the dosages applied.
People with pulmonary fibrosis often experience a protracted time to diagnosis, high symptom burden and limited disease information. This review aimed to identify the supportive care needs reported ...by people with pulmonary fibrosis and their caregivers.
A systematic review was conducted according to PRISMA guidelines. Studies that investigated the supportive care needs of people with pulmonary fibrosis or their caregivers were included. Supportive care needs were extracted and mapped to eight pre-specified domains using a framework synthesis method.
A total of 35 studies were included. The most frequently reported needs were in the domain of information/education, including information on supplemental oxygen, disease progression and prognosis, pharmacological treatments and end-of-life planning. Psychosocial/emotional needs were also frequently reported, including management of anxiety, anger, sadness and fear. An additional domain of "access to care" was identified that had not been specified
; this included access to peer support, psychological support, specialist centres and support for families of people with pulmonary fibrosis.
People with pulmonary fibrosis report many unmet needs for supportive care, particularly related to insufficient information and lack of psychosocial support. These data can inform the development of comprehensive care models for people with pulmonary fibrosis and their loved ones.
The relationship between vitamin D deficiency with dental caries, periodontitis and oral cancer is controversial.
This review aimed to systematically evaluate the published literature and summarise ...the available evidence about the impact of vitamin D deficiency (VDD) on the oral diseases mentioned above.
PubMed, Web of Science, Scopus and ScienceDirect databases were used. The search terms included were vitamin D, caries, periodontitis, and oral cancer. All papers published between January 2017 and November 2022 were included. The PRISMA process was used for the screening and selection studies.
Initially, 3001 studies were identified. However, after evaluating 46 full-text articles that explored the link between VDD and caries, periodontitis, and oral cancer, only 32 studies met the inclusion criteria for this systematic review. Among these, 15 studies focused on caries, 16 on periodontitis, and only one on oral cancer. Regarding study quality and risk of bias, 25 out of the 32 studies were deemed to have low risk. A total of 12 studies on periodontitis showed the impact of VDD.
The review highlights that most evidence suggests an association between VDD and periodontitis. However, findings concerning the association between VDD and dental caries were controversial. Thus, further research is required to clarify the impacts of VDD on caries and oral cancer.
•A pioneering study exploring self-regulatory practices amongst motorcycle riders.•Motorcycle riders were found to be at risk of crash involvement and riding cessation.•Behavioural and psychological ...factors were important contributors to self-regulation.•Interventions should be customised to cater for populations with mixed travel modes.
The ability to drive longer and safely are crucial for many older adults. There is a growing evidence on self-regulatory practices amongst older drivers in developed countries, but limited studies are conducted in developing countries. This study aimed to explore self-regulatory practices amongst older Malaysian car drivers and motorcycle riders.
A cross-sectional study was conducted amongst older adults aged 60 years and above residing in two states located in the west coast of Peninsular Malaysia using a self-administered questionnaire. Stepwise regressions were performed to identify for key factors associated with driving/riding self-regulation and crash involvement. Multilevel modelling was conducted to examine the clustering effect of respondents recruited from the two states.
Six-hundred and thirty-seven respondents completed the questionnaire, with over three-quarters of them still driving/riding at the time of data collection. Physical fitness, behavioural and psychological changes experienced with advancing age were important motivators towards self-regulation. Motorcycle riders were found to be at a higher risk of crash involvement, and they were more prone to cease riding compared to car drivers.
Self-regulatory practices amongst older car drivers and motorcycle riders were found to be different. As such, there is a need to customise evidenced-based approaches to cater for specific age groups and road users, particularly in a developing country like Malaysia, where motorcycle is often considered as an affordable mode of transport and is largely involved in road traffic crashes.
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