Comparison of Mitochondrial Adenosine Triphosphate-Sensitive Potassium Channel High- vs Low-Affinity Sulfonylureas and Cardiovascular Outcomes in Patients With Type 2 Diabetes Treated With Metformin.

Importance: Sulfonylureas are frequently used as add-on to metformin in type 2 diabetes (T2D), and individual sulfonylurea agents carry different risks of cardiovascular disease. Sulfonylureas' different affinities to cardiac mitochondrial adenosine triphosphate-sensitive potassium (mitoKATP) channels have been speculated to account for the intraclass difference in cardiovascular risk from in vitro and ex vivo studies; however, this hypothesis has not been assessed in a general population with diabetes receiving sulfonylureas added to metformin. Objective: To compare the risk of myocardial infarction (MI), ischemic stroke, or cardiovascular death in patients with T2D treated with mitoKATP channel high-affinity sulfonylureas and low-affinity sulfonylureas as add-on to metformin. Design, Setting, and Participants: This is a new-user, active-comparator, and propensity score-matched cohort study with analysis of the Taiwanese Diabetes Mellitus Health Database from 2006, to 2017. Data analysis was performed from August 2020 to July 2021. Exposures: Cardiac mitoKATP channel high-affinity (glyburide and glipizide) and low-affinity (gliclazide and glimepiride) sulfonylureas combined with metformin. Main Outcomes and Measures: Primary outcome was major adverse cardiovascular events (MACEs), a composite of cardiovascular death or hospitalization for either MI or ischemic stroke. Secondary outcomes included individual MACE components, heart failure, arrhythmia, all-cause mortality, and severe hypoglycemia. Cox proportional hazards models were used to estimate adjusted hazard ratios (aHRs). Results: Each sulfonylurea group comprised 53 714 patients (mean [SD] age, 54.7 [12.1] years; 31 962 men [59.5%]). MitoKATP channel high-affinity sulfonylureas vs low-affinity sulfonylureas when combined with metformin were associated with an increased risk of MACE (aHR, 1.18; 95% CI, 1.03-1.34), MI (aHR, 1.34; 95% CI, 1.04-1.73), all-cause mortality (aHR, 1.27; 95% CI, 1.03-1.57), and severe hypoglycemia (aHR, 1.82; 95% CI, 1.58-2.10), but not with increased risks of ischemic stroke, cardiovascular death, arrhythmia, and heart failure. The duration analyses revealed the highest MACE risk during 1 to 90 days after initiation of mitoKATP channel high-affinity sulfonylureas (aHR, 6.06; 95% CI, 4.86-7.55). Conclusions and Relevance: Use of mitoKATP channel high-affinity sulfonylureas vs low-affinity sulfonylureas was associated with an increased MACE risk in patients with T2D concomitantly receiving metformin, suggesting that high-affinity blockage of the mitoKATP channels could account for sulfonylurea-associated MACEs.

Relationship between Ideal Cardiovascular Health and Incident Proteinuria: A 5 Year Retrospective Cohort Study.

The objective of this study was to examine whether a higher number of ideal cardiovascular health (CVH) metrics are beneficial for lowering the risk of proteinuria. This is a retrospective cohort study with an average follow-up of 5 years. Participants between 21 and 75 years old and without a history of cardiovascular disease and proteinuria were enrolled. CVH metrics, including smoking, diet, physical activity, blood pressure, body mass index (BMI), cholesterol, and fasting glucose, were assessed by questionnaires, physical examination, and blood analysis. Proteinuria was assessed by dipstick measurement. During the follow-up period, 169,366 participants were enrolled, and 1481 subjects developed proteinuria. A higher number of ideal CVH metrics was related to a lower risk of proteinuria after adjustment. Among the components of CVH metrics, ideal blood pressure (HR = 0.33, 95% CI = 0.25-0.43), fasting glucose (HR = 0.17, 95% CI = 0.12-0.22), and BMI (HR = 0.20, 95% CI = 0.15-0.27) had beneficial effects on proteinuria. Despite no significant benefit of diet score, the corresponding lower sodium intake showed a lower risk of proteinuria (HR = 0.58, 95% CI = 0.43-0.79). Incident proteinuria was inversely related to the number of ideal CVH metrics. CVH metrics may be a predictor of proteinuria, and achieving a higher number of ideal scores should be recommended as a proteinuria prevention strategy.

Arthrospira Enhances Seroclearance in Patients with Chronic Hepatitis B Receiving Nucleos(t)ide Analogue through Modulation of TNF-α/IFN-γ Profile.

Chronic hepatitis B (CHB) virus infection, causing immune dysfunction and chronic hepatitis, is one of the leading risk factors for hepatocellular cancer. We investigated how Arthrospira affected hepatitis B surface antigen (HBsAg) reduction in CHB patients under continued nucleos(t)ide analogues (NA). Sixty CHB patients who had been receiving NA for at least one year with undetectable HBV DNA were randomized into three groups: control and oral Arthrospira at 3 or 6 g daily add-on therapy groups. Patients were followed up for 6 months. Oral Arthrospira-diet mice were established to investigate the possible immunological mechanism of Arthrospira against HBV. Within 6 months, mean quantitative HBsAg (qHBsAg) decreased in the oral Arthrospira add-on therapy group. Interestingly, interferon gamma (IFN-γ) increased but TNF-α, interleukin 6 (IL-6), hepatic fibrosis, and steatosis decreased in the add-on groups. In mice, Arthrospira enhanced both innate and adaptive immune system, especially natural killer (NK) cell cytotoxicity, B cell activation, and the interleukin 2 (IL-2), IFN-γ immune response. Arthrospira may modulate IL-2- and TNF-α/IFN-γ-mediated B and T cell activation to reduce HBsAg. Also, Arthrospira has the potential to restore immune tolerance and enhance HBsAg seroclearance in CHB patients through promoting T, B, and NK cell activation.

Association Between Ideal Cardiovascular Health and Vegetarian Dietary Patterns Among Community-Dwelling Individuals.

Background: Vegetarians have been shown to have better metabolic profiles than non-vegetarians, and vegetarianism has potential beneficial effects on cardiovascular disease. However, there is a lack of studies on vegetarians that examine both metabolic profiles and lifestyle habits, such as physical activity, smoking habits, and dietary patterns, which are equally important in the context of cardiovascular disease. We explored whether a vegetarian diet is associated with both metabolic traits and lifestyle habits by assessing cardiovascular health (CVH) metrics. Methods: This was a cross-sectional study conducted in a Taiwanese population. Data collected between 2000 and 2016 were extracted from the MJ Health database. Participants aged 40 years and older without cardiovascular disease were included. CVH metrics included smoking habits, blood pressure, total cholesterol, serum glucose, body mass index, physical activity, and healthy diet score. Vegetarian participants were full-time vegetarians who did not consume meat or fish. All the data were assessed from self-report questionnaires, physical examinations, and blood analyses following standard protocol. Multiple logistic regression analysis was used to evaluate the association between vegetarianism and CVH metrics. Results: Of 46,287 eligible participants, 1,896 (4.1%) were vegetarian. Overall, vegetarians had better CVH metrics (OR = 2.09, 95% CI = 1.84-2.37) but lower healthy diet scores (OR = 0.41, 95% CI = 0.33-0.51) after adjustment. No difference in physical activity (OR = 0.86, 95% CI = 0.73-1.02) was identified between vegetarians and non-vegetarians. Additionally, vegetarians had higher whole grain intake (OR = 2.76, 95% CI = 2.28-3.35) and lower sugar-sweetened beverage consumption (OR = 1.36, 95% CI = 1.18-1.58). Conclusions: Our results suggested that vegetarians had better overall ideal CVH metrics but lower ideal healthy diet scores than non-vegetarians, which was likely due to the lack of fish consumption in this population group. When assessing CVH metrics and healthy diet scores for vegetarians, metrics and scores chosen should be suitable for use with vegetarian populations.

Relationship between ideal cardiovascular health metrics and hearing loss: A 10-year retrospective cohort study.

OBJECTIVE: The role of ideal cardiovascular health (CVH) metrics in developing hearing loss remains uncertain. Thus, our objective was to analyse the connection between hearing loss and ideal CVH metrics in a 10-year retrospective cohort. STUDY DESIGN: Retrospective cohort study. SETTING: A health management centre in Taiwan. PARTICIPANTS: Participants who underwent the first annual health check-up between 2000 and 2006 and with a follow-up check-up more than ten years later. MAIN OUTCOME MEASURES: Hearing thresholds were measured at 500 Hz, 1000 Hz, 2000 Hz and 4000 Hz. Individuals with a best ear pure-tone audiometry four-frequency average of >25 dB HL were defined as having hearing loss. The ideal CVH metrics were classified into 7 categories based on the American Heart Association's definition. The associations of hearing loss with the sum of the ideal CVH metrics and each ideal CVH metric were examined by multiple logistic regression analysis. RESULTS: The present study consisted of 6974 participants. The 10-year follow-up showed that the odds ratio (OR) of hearing loss was .74 for participants with 5-7 ideal CVH metrics (95% CI, .59-.93, p = .01) compared with those with 0-2 ideal CVH metrics. Among the CVH metrics, participants with an ideal smoking status might have reduced odds of developing hearing loss; the OR was .72 (95% CI, .58-.89, p = .003). CONCLUSIONS: Participants with an increased number of ideal CVH metrics and better performance on the smoking metric had a significantly protective effect regarding hearing loss development.

The Polymorphism at PLCB4 Promoter (rs6086746) Changes the Binding Affinity of RUNX2 and Affects Osteoporosis Susceptibility: An Analysis of Bioinformatics-Based Case-Control Study and Functional Validation.

Purpose: Genome-wide association studies have identified numerous genetic variants that are associated with osteoporosis risk; however, most of them are present in the non-coding regions of the genome and the functional mechanisms are unknown. In this study, we aimed to investigate the potential variation in runt domain transcription factor 2 (RUNX2), which is an osteoblast-specific transcription factor that normally stimulates bone formation and osteoblast differentiation, regarding variants within RUNX2 binding sites and risk of osteoporosis in postmenopausal osteoporosis (PMOP). Methods: We performed bioinformatics-based prediction by combining whole genome sequencing and chromatin immunoprecipitation sequencing to screen functional SNPs in the RUNX2 binding site using data from the database of Taiwan Biobank; Case-control studies with 651 postmenopausal women comprising 107 osteoporosis patients, 290 osteopenia patients, and 254 controls at Tri-Service General Hospital between 2015 and 2019 were included. The subjects were examined for bone mass density and classified into normal and those with osteopenia or osteoporosis by T-scoring with dual-energy X-ray absorptiometry. Furthermore, mRNA expression and luciferase reporter assay were used to provide additional evidence regarding the associations identified in the association analyses. Chi-square tests and logistic regression were mainly used for statistical assessment. Results: Through candidate gene approaches, 3 SNPs in the RUNX2 binding site were selected. A novel SNP rs6086746 in the PLCB4 promoter was identified to be associated with osteoporosis in Chinese populations. Patients with AA allele had higher risk of osteoporosis than those with GG+AG (adjusted OR = 6.89; 95% confidence intervals: 2.23-21.31, p = 0.001). Moreover, the AA genotype exhibited lower bone mass density (p < 0.05). Regarding mRNA expression, there were large differences in the correlation between PLCB4 and different RUNX2 alleles (Cohen's q = 0.91). Functionally, the rs6086746 A allele reduces the RUNX2 binding affinity, thus enhancing the suppression of PLCB4 expression (p < 0.05). Conclusions: Our results provide further evidence to support the important role of the SNP rs6086746 in the etiology of osteopenia/osteoporosis, thereby enhancing the current understanding of the susceptibility to osteoporosis. We further studied the mechanism underlying osteoporosis regulation by PLCB4.

Prediction of a Competing Endogenous RNA Co-expression Network by Comprehensive Methods in Systemic Sclerosis-Related Interstitial Lung Disease.

Systemic sclerosis (SSc) is an immune-mediated connective tissue disease characterized by fibrosis of multi-organs, and SSc-related interstitial lung disease (SSc-ILD) is a leading cause of morbidity and mortality. To explore molecular biological mechanisms of SSc-ILD, we constructed a competing endogenous RNA (ceRNA) network for prediction. Expression profiling data were obtained from the Gene Expression Omnibus (GEO) database, and differential expressed mRNAs and miRNAs analysis was further conducted between normal lung tissue and SSc lung tissue. Also, the interactions of miRNA-lncRNA, miRNA-mRNA, and lncRNA-mRNA were predicted by online databases including starBase, LncBase, miRTarBase, and LncACTdb. The ceRNA network containing 11 lncRNAs, 7 miRNAs, and 20 mRNAs were constructed. Based on hub genes and miRNAs identified by weighted correlation network analysis (WGCNA) method, three core sub-networks-SNHG16, LIN01128, RP11-834C11.4(LINC02381)/hsa-let-7f-5p/IL6, LINC01128/has-miR-21-5p/PTX3, and LINC00665/hsa-miR-155-5p/PLS1-were obtained. Combined with previous studies and enrichment analyses, the lncRNA-mediated network affected LPS-induced inflammatory and immune processes, fibrosis development, and tumor microenvironment variations. The ceRNA network, especially three core sub-networks, may be served as early biomarkers and potential targets for SSc, which also provides further insights into the occurrence, progression, and accurate treatment of SSc at the molecular level.

Two mitochondrial genomes of Taiwanese rhinoceros beetles, Oryctes rhinoceros and Eophileurus chinensis (Coleoptera: Scarabaeidae).

Two mitochondrial genomes of the dynastine beetles, Oryctes rhinoceros (Linnaeus, 1758) and Eophileurus chinensis (Faldermann, 1835), were assembled via high-throughput sequencing (HTS). Each of the mitogenomes has 37 genes, showing standard gene order and annotation as the other insects, except for the transfer genes, presenting tQ-tI-tM order. To examine their phylogenetic positions, 118 public mitogenomes of Scarabaeidae were used to infer a ML tree. Overall, our scarabaeid phylogeny reveals clear relationships with high nodal supports, and the two rhinoceros beetles are both grouped with the subfamily Dynastinae. The feeding habit of the two clades seems to represent coprophagous and phytophagous types. However, polyphyletic relationships were observed in the subfamily Melolothinae and in the tribes of Onthophagini and Oniticellini. Further systematic revision is needed.

Hypermethylation of SHISA3 DNA as a blood-based biomarker for colorectal cancer.

In Taiwan, colorectal cancer (CRC) is the second most common cancer and the cancer with the third highest mortality rate. This may be because of the difficulty of detecting the disease in the early stages, as well as the fact that colonoscopy, a typical method used in screening for CRC, causes discomfort to the recipient and is prone to technical interference. For the earlier detection of CRC, finding an easier screening method with a simpler collection procedure is essential. Thus, in the present study, plasma samples from patients with CRC were analyzed to determine the extent of methylation in SHISA3 DNA. Studies have suggested that SHISA3, a newly identified tumor suppressor, can regulate tumor growth, and that the inactivation of its DNA can be traced to epigenomic alterations in CRC. Another study reported the presence of hypermethylated SHISA3 DNA in CRC biopsy specimens. In the present study, the plasma of 30 patients with CRC and nine healthy controls was collected and analyzed for the concentration of cell-free DNA through bisulfite sequencing. The methylation rates were determined. Our results have shown that an increasing amount of cell-free DNA in the group of CRC patient's plasma compared to the healthy group. Moreover, patients with later stages of CRC had higher concentrations of cell-free DNA. Notably, the methylation rate of SHISA3 was higher in the plasma of the CRC group than in that of the healthy group. The results indicated that the presence of tumor cells does not reduce the degree of SHISA3 DNA in the peripheral blood of patients with CRC. In other words, the hypermethylation of SHISA3, which inactivates the gene, is a potential cause of tumorigenesis. Furthermore, the methylation rate of SHISA3 DNA was higher in the plasma of patients with stage II CRC than in that of those with stage I CRC. In conclusion, the combination of conventional testing and screening for SHISA3 hypermethylation in plasma could improve the rate at which CRC is detected.

Improving Interlaminar Fracture Toughness and Impact Performance of Carbon Fiber/Epoxy Laminated Composite by Using Thermoplastic Fibers.

The effects of thermoplastic polyimide (PI) and polypropylene (PP) fibers and areal density of toughened layer on interlaminar fracture toughness and impact performance of carbon fiber/epoxy (CF/EP) laminated composites were studied. Mode I interlaminar fracture toughness (GIC) was analyzed via double cantilever beam (DCB) tests. When comparing for the toughener type, PI played a positive role in enhancing the mode-I fracture toughness, while PP was not effective due to the less fiber bridge formed during composite curing. The toughening effects of areal density of PI were further investigated by end notched flexure (ENF) testing and low velocity impact testing to better understand the toughening mechanisms. The results revealed that the toughening effect reached its best effectiveness when the areal density of toughened layer was 30 g/m2. Compared with the control group, GIC and GIIC of CF/EP laminated composite were increased by 98.49% and 84.07%, and Fmax and Ee were enhanced by 92.38% and 299.08% under low velocity impact. There is no obvious delamination phenomenon on the surface of laminates after low velocity impact, indicating the improved interlaminar and impact performance of laminated composite.

Hypertension control and risk of colonic diverticulosis.

BACKGROUND: The prevalence of diverticulosis has increased in our aging population, but the risk factors for diverticulosis are not fully understood. The role of hypertension in the risk of diverticulosis remains uncertain. This study investigated whether hypertension is associated with asymptomatic colorectal diverticulosis. METHODS: This study enrolled asymptomatic patients who received a colonoscopy as part of a health check. Hypertension was defined by actual measured blood pressure. Logistic regression models were used to examine the relationship between hypertension and diverticulosis. In addition, we established three logistic regression models for covariate adjustment, and further stratified patients with hypertension into three subgroups based on their type of hypertension. RESULTS: The study group consisted of 2748 participants, including 141 participants with diverticulosis and 2607 participants without diverticulosis. After adjustments for potential covariates, the odds ratio (OR) for having diverticulosis was 1.83 (95% confidence interval, 1.21-2.75, p = 0.004) in the hypertension group compared with the group without hypertension. In subgroup analyses, hypertension without antihypertensive medication use, and hypertension despite the use of antihypertensive medication were also significantly associated with the occurrence of asymptomatic diverticulosis (OR = 1.73, p = 0.028; OR = 2.07, p = 0.013, respectively). Current normal blood pressure under antihypertensive drug therapy was not associated with diverticulosis (OR = 1.74, p = 0.092). CONCLUSIONS: Our findings suggest a positive association between hypertension and diverticulosis. Participants with poorly controlled blood pressure were found to have a higher risk of asymptomatic diverticulosis. Our study presents epidemiologic evidence for future prevention strategies against diverticulosis.

Neutrophil to lymphocyte ratio as predictor for incident hypertension: a 9-year cohort study in Taiwan.

The neutrophil-to-lymphocyte ratio (NLR) has received much attention in recent decades and has been a novel inflammatory marker. NLR has been applied in predicting the prognosis of malignancies, mortality, and chronic diseases. Additionally, hypertension, defined as systolic blood pressure ≥ 140 mm Hg or diastolic blood pressure ≥ 90 mm Hg, a previous diagnosis of hypertension, and taking any antihypertensive drug, has been one of the most common chronic diseases in Asia and is currently the most important risk factor for cardiovascular diseases worldwide. Thus, we aimed to investigate the correlation between NLR and prevalent hypertension in the Taiwanese population. From the data of routine health checkups at the General Health Promotion Center in the Tri-Service General Hospital (TSGH), a total of 6278 participants were included. The NLR value was divided into tertiles. The Cox regression model revealed that the highest NLR group tended to be hypertensive (HR = 1.28, 95% CI 1.03-1.59) after adjustment. Individuals were also divided into age-specific, BMI-specific, or sex-specific groups; compared with the lowest NLR group, elderly individuals in the highest tertile of NLR were relatively likely to be hypertensive after covariate adjustment (HR = 1.88, 95% CI 1.19-2.96). Furthermore, a male group aged more than 60 years was reported to have a significant association with hypertension (HR = 1.84, 95% CI 1.06-3.18). However, there was no significant difference in the BMI-based stratified groups, even after adjustment. Our research revealed a significant association between the NLR and incident hypertension, especially in elderly or male Taiwanese individuals.

Unravelling relationships among the shared stripes of sailors: Mitogenomic phylogeny of Limenitidini butterflies (Lepidoptera, Nymphalidae, Limenitidinae), focusing on the genera Athyma and Limenitis.

The phylogenetic relationships of the nymphalid butterfly tribe Limenitidini are best known for the genera Limenitis and Adelpha, model taxa for evolutionary processes such as Batesian mimicry and rapid adaptive radiations. Whereas these American limenitidines have received the most attention, phylogenetic relationships of their Asian relatives are still controversial and largely unexplored. Even one of the largest genera in Asia, Athyma, is polyphyletic. To clarify the phylogenetic relationships of these Asian Limenitidini, a total of 53 representatives were sampled; 37 have their mitogenomes sequenced for the first time. Our phylogenetic results confirm that mitogenomic data provides well-resolved relationships at most major levels of the phylogeny, even using different partition schemes or different inference methods. Interestingly, our results show that some Athyma taxa are embedded within the genus Limenitis, whereas the genus Tacola, previously considered to be a synonym of Athyma, needs to be recognized as a valid clade. Additionally, the other Limenitidini genera in Asia (namely Tarattia, Litinga, Sumalia, Pandita and Patsuia) are now grouped either within Athyma or Limenitis, so these genera need to be sunk. Importantly, we also show that the mainly Old World Limenitis and entirely New World Adelpha are sister groups, confirming the relevance of Asian lineages to global studies of Limenitis evolution.

Platelet-derived growth factor-AA is a substantial factor in the ability of adipose-derived stem cells and endothelial progenitor cells to enhance wound healing.

Nonhealing wounds with various forms of complications have been a major challenge for patients with different diseases, and few data are available regarding the clinical significance of platelet-derived growth factor-AA (PDGF-AA) in the enhanced wound healing with stem cells, and the precise molecular mechanism remains unclear. The study aims to investigate the role of PDGF-AA in adipose-derived stem cells (ASCs) and endothelial progenitor cells (EPCs) enhancing wound healing. In this study, ASCs and EPCs were applied to treat wounds in an animal wound model with a wound-healing assay. We knocked down PDGF-AA expression in ASCs using the PDGF-AA short hairpin RNA technique and investigated the related molecular mechanism. The wound model and wound-healing assay of the study showed that transplantation of ASCs could enhance wound healing. The results showed that the PDGF-AA knockdown ASC group had much less improvement of wound healing than other groups treated with wild-type ASCs in wound tissues. The regulation of PDGF-AA in ASCs may contribute to improve wound healing through the PI3K/Akt/eNOS signaling pathway. The data indicated that PDGF-AA might play a vital role in ASCs and EPCs enhancing wound healing, possibly by its effects on angiogenesis. It would be a potential approach using PDGF-AA for clinical treatment of chronic wounds.-Wu, L.-W., Chen, W.-L., Huang, S.-M., Chan, J. Y.-H. Platelet-derived growth factor AA is a substantial factor in the ability of adipose-derived stem cells and endothelial progenitor cells to enhance wound healing.

Mid-arm muscle circumference: A significant factor of all-cause and cancer mortalities in individuals with elevated platelet-to-lymphocyte ratio.

Platelet-to-lymphocyte ratio (PLR) is an inflammatory maker, and high PLR is associated with mortality in several diseases. The predictors of mortality in individuals with high PLR is still lacking. Our aims were to assess if mid-arm muscle circumference (MAMC) can predict all-cause mortality, cancer mortality, and cardiovascular mortality in individuals with high PLR. Adult participants from the National Health and Nutrition Examination Survey III (1988-1994) were included. All participants were divided into low PLR and high PLR groups with the cut-off point being the median PLR level, and each group was evaluated for risk factors of mortality. MAMC was divided into tertiles and the general characteristics of the study population related to MAMC were evaluated. The study included 14,221 adults with 6,701 (47.1%) male and 7,520 (52.9%) female participants. The median PLR ratio was 122. Higher levels of systolic blood pressure, total triglycerides, total cholesterol, low-density lipoprotein, C-reactive protein, uric acid, and glucose, as well as a higher age, were associated with increased risk of mortality in both groups. After adjusting for all the covariates, in the higher PLR group, the highest MAMC tertile was significantly associated with lower hazard ratios for all-cause and cancer mortalities compared with the lowest MAMC tertile. However, this association was not observed in the low PLR group. The highest MAMC tertile showed protective effects from all-cause and cancer mortalities compared with the lowest MAMC tertile in individuals with PLR ≥ 122. In conclusion, the highest MAMC tertile was significantly associated with decreasing HRs for all-cause and cancer mortalities compared with the lowest MAMC tertile in individuals with elevated PLR.

Mid-arm muscle circumference as a substantial factor against mortality among people with elevated gamma gaps.

Gamma gap is the difference in total serum proteins and albumin and an elevated gamma gap is related to infections, malignancy, and rheumatic diseases. An elevated gamma gap is also associated with higher mortality due to the correlation with inflammatory status. The study aimed to utilize mid-arm muscle circumference (MAMC) to assist in predicting all-cause mortality, cancer mortality, and cardiovascular mortality in people with elevated gamma gaps. Data were obtained from the third U.S. National Health and Nutrition Examination Survey (1988-1994), which contained 14,011 adults aged 20 to 90 years during up to 14.3 years of follow-up. The Primary analysis examined MAMC in tertiles and revealed the demographic and characteristics of the study population. Receiver operating characteristic curve analysis was used and the most suitable cut-off point of gamma gap was 3.65 g/dl. The secondary analysis employed Cox proportional hazards models stratified by age, gender and body mass index to evaluate the hazard ratios for all-cause mortality, cancer mortality, and cardiovascular mortality associated with the MAMC. As the MAMC tertiles increased in group with gamma gap ≥ 3.65 g/dl, individuals with elder age (60-90 years), normal range of body mass index (19-24.9 kg/m2), and male gender tended to have lower hazard ratios for all-cause mortality, cancer mortality, and cardiovascular mortality. These substantial findings indicate that higher MAMC may be a protective factor of all cause-mortality, cancer mortality, and cardiovascular mortality among older male with normal body mass index and elevated gamma gaps.

Does the Additional Component of Calf Circumference Refine Metabolic Syndrome in Correlating With Cardiovascular Risk?

Context: Calf circumference (CC) was a useful anthropometric tool, but there was limited study on the effect of CC on metabolic syndrome (MetS) for cardiovascular risk. Objective: The objective of our study was to determine whether adding CC as a component of MetS refined correlating MetS with cardiovascular, all-cause, and cancer mortality risks. Design, Setting, Patients, and Interventions: From the National Health and Nutrition Examination Survey data set for 1999 through 2002, we analyzed four types of MetS: (1) increased waist circumference and two or more of four MetS components (WaistMetS); (2) decreased CC and two or more of four MetS components (CalfMetS); (3) increased waist-to-calf ratio and two or more of four MetS components (WCRMetS); and (4) decreased CC and three or more of five MetS components (CC+MetS). Primary Outcome Measure: The cause-specific hazard ratios were measured as categorized by the four types of MetS. Results: For cardiovascular mortality, the adjusted hazard ratios for WaistMetS, CalfMetS, WCRMetS, and CC+MetS were 1.867, 1.871, 1.949, and 2.306, respectively (all P < 0.001). Notably, CalfMetS showed the strongest positive correlation with serum C-reactive protein levels, and WCRMetS had the strongest positive relationship with homeostasis model assessment of insulin resistance. Conclusions: Adding CC to the components of MetS correlated with higher cardiovascular and all-cause mortality risk than the traditional definition of MetS.

Investigating the mincing method for isolation of adipose-derived stem cells from pregnant women fat.

The success of stem cell application in regenerative medicine, usually require a stable source of stem or progenitor cells. Fat tissue represents a good source of stem cells because it is rich in stem cells and there are fewer ethical issues related to the use of such stem cells, unlike embryonic stem cells. Therefore, there has been increased interest in adipose-derived stem cells (ADSCs) for tissue engineering applications. Here, we aim to provide an easy processing method for isolating adult stem cells from human adipose tissue harvested from the subcutaneous fat of the abdominal wall during gynecologic surgery. We used a homogenizer to mince fat and compared the results with those obtained from the traditional cut method involving a sterile scalpel and forceps. Our results showed that our method provides another stable and quality source of stem cells that could be used in cases with a large quantity of fat. Furthermore, we found that pregnancy adipose-derived stem cells (P-ADSCs) could be maintained in vitro for extended periods with a stable population doubling and low senescence levels. P-ADSCs could also differentiate in vitro into adipogenic, osteogenic, chondrogenic, and insulin-producing cells in the presence of lineage-specific induction factors. In conclusion, like human lipoaspirates, adipose tissues obtained from pregnant women contain multipotent cells with better proliferation and showed great promise for use in both stem cell banking studies as well as in stem cell therapy.

Higher Platelet-to-Lymphocyte Ratio Increased the Risk of Sarcopenia in the Community-Dwelling Older Adults.

The platelet-to-lymphocyte ratio (PLR) has been extensively studied in oncologic diseases. However, the correlation between PLR and sarcopenia remains unknown. In this cross-sectional analysis, we enrolled 3,671 non-institutionalized individuals from the National Health and Nutrition Examination Survey (NHANES) III (1988-1994) aged ≥60 years and whose complete blood counts (CBCs), body composition measurements, and related demographic information was available. Skeletal muscle mass was assessed using a previously published equation (including age, sex, height, and bioelectrical impedance analysis). PLR values were estimated based on laboratory data. Multiple linear and logistic regression analyses, quartile-based stratified odds ratio comparisons, and trend tests were performed. Elevations in serum PLR values were significantly associated with sarcopenia status and negatively associated with skeletal muscle index. After additionally adjusting for other covariates, the significant negative correlation remained; moreover, participants with highest serum PLR values (≥155) had 2.36 times greater risk of sarcopenia than those with lowest PLR values (<90; odds ratio (OR) = 2.36; 95% confidence interval (CI): 1.21-3.31; p < 0.01). Higher PLR levels are associated with a greater risk of sarcopenia in geriatric populations. Thus, PLR as an inexpensive and easily measurable parameter can be considered as an inflammatory biomarker for sarcopenia.

Elevated serum tartrate-resistant acid phosphatase isoform 5a levels in metabolic syndrome.

BACKGROUND: Tartrate-resistant phosphatase isoform 5a is expressed in tumor-associated macrophages and is a biomarker of chronic inflammation. Herein, we correlated serum tartrate-resistant phosphatase isoform 5a levels with metabolic syndrome status and made comparisons with traditional markers of inflammation, including c-reactive protein and interleukin-6. METHODS: One hundred healthy volunteers were randomly selected, and cut-off points for metabolic syndrome related inflammatory biomarkers were determined using receiver operating characteristic curves. Linear and logistic regression models were subsequently used to correlate inflammatory markers with the risk of metabolic syndrome. RESULTS: Twenty-two participants met the criteria for metabolic syndrome, and serum tartrate-resistant phosphatase isoform 5a levels of >5.8 µg/L were associated with metabolic syndrome (c-statistics, 0.730; p = 0.001; 95% confidence interval, 0.618-0.842). In addition, 1 µg/L increases in tartrate-resistant phosphatase isoform 5a levels were indicative of a 1.860 fold increase in the risk of metabolic syndrome (p = 0.012). CONCLUSIONS: Elevated serum tartrate-resistant phosphatase isoform 5a levels are associated with the risk of metabolic syndrome, with a cut-off level of 5.8 µg/L.