Appendicular lean tissue mass and the prevalence of sarcopenia among healthy women.

Studies indicate that deficient skeletal muscle mass or sarcopenia is a major cause of disability and morbidity among the elderly. In part, due to the lack of generally applicable normal values, there is still insufficient epidemiologic data available on the frequency and severity of sarcopenia in health and under various disease-related conditions. The objectives of the present study were to (1) characterize the age- and menopause-related variations in appendicular lean tissue mass (LTM(A)), (2) provide young-normal means and estimate the age-specific prevalence of sarcopenia among healthy women. A total of 754 healthy women were included in the study of cross-sectional design. LTM(A) was estimated by dual-energy x-ray absorptiometry (DEXA). Physical characteristics and menopausal status were also registered. LTM(A) as well as height showed significant negative correlation with age with Pearson's r values of -0.43 and -0.06, respectively (P <.05). Trend of finding lower mean values with advancing age remained even when LTM(A) was adjusted for height(2) (ht(2)). Menopause did not seem to have any influence on LTM(A). Young-normal means were obtained from 216 premenopausal women aged 18 to 39 years. Prevalence rates of sarcopenia in healthy women were determined with reference to a cut-off line corresponding to LTM(A) or LTM(A)/ht(2) less than young-normal mean 2 SD and were found to be 40.2% and 12.3%, respectively, among the healthy elderly (>70 years of age). Results of the present study provide further evidence that sarcopenia exists even among otherwise healthy women with increasing age-specific prevalence. Further studies are needed (1) to estimate the prevalence of sarcopenia under various health and disease-related conditions with reference to the hereby given cut-off values and (2) to find therapeutic strategies with beneficial effects in conserving skeletal muscle mass.     

Intestinal mucosa permeability following oral insulin delivery using core shell corona nanolipoparticles

Chitosan nanoparticles (NC) have excellent capacity for protein entrapment, favorable epithelial permeability, and are regarded as promising nanocarriers for oral protein delivery. Herein, we designed and evaluated a class of core shell corona nanolipoparticles (CSC) to further improve the absorption through enhanced intestinal mucus penetration. CSC contains chitosan nanoparticles as a core component and pluronic F127-lipid vesicles as a shell with hydrophilic chain and polyethylene oxide PEO as a corona. These particles were developed by hydration of a dry pluronic F127-lipid film with NC suspensions followed by extrusion. Insulin nested inside CSC was well protected from enzymatic degradation. Compared with NC, CSC exhibited significantly higher efficiency of mucosal penetration and, consequently, higher cellular internalization of insulin in mucus secreting E12 cells. The cellular level of insulin after CSC treatment was 36-fold higher compared to treatment with free insulin, and 10-fold higher compared to NC. CSC significantly facilitated the permeation of insulin across the ileum epithelia, as demonstrated in an ex vivo study and an in vivo absorption study. CSC pharmacological studies in diabetic rats showed that the hypoglycemic effects of orally administrated CSC were 2.5-fold higher compared to NC. In conclusion, CSC is a promising oral protein delivery system to enhance the stability, intestinal mucosal permeability, and oral absorption of insulin.     

The emotional impact of the COVID-19 pandemic on individuals with progressive multiple sclerosis

Journal of Neurology - Individuals with pre-existing chronic illness have shown increased anxiety and depression due to COVID-19. Here, we examine the impact of the COVID-19 pandemic on emotional...     

Mutated Desmoglein‐2 Proteins are Incorporated into Desmosomes and Exhibit Dominant‐Negative Effects in Arrhythmogenic Right Ventricular Cardiomyopathy

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a hereditary cardiac condition associated with ventricular arrhythmias, heart failure, and sudden death. The most frequent ARVC genes encode desmosomal proteins of which mutations in desmoglein‐2 (DSG2), account for 10%–20% of cases. This study aimed to investigate how DSG2 mutations contribute to the pathogenesis of ARVC. Initial mutation analysis of DSG2 in 71 probands identified the first family reported with recessively inherited ARVC due to a missense mutation. In addition, three recognized DSG2 mutations were identified in 12 families. These results and further mutation analyses of four additional desmosomal genes indicated that ARVC caused by DSG2 mutations is often transmitted by recessive or digenic inheritance. Because desmosomal proteins are also expressed in skin tissue, keratinocytes served as a cell model to investigate DSG2 protein expression by Western blotting, 2D‐PAGE, and liquid chromatography–mass spectrometry. The results showed that heterozygous mutation carriers expressed both mutated and wild‐type DSG2 proteins. These findings were consistent with the results obtained by immunohistochemistry of endomyocardial biopsies and epidermal tissue of mutation carriers, which indicated a normal cellular distribution of DSG2. The results suggested a dominant‐negative effect of the mutated DSG2 proteins because they were incorporated into the desmosomes.     

Profiling receptor tyrosine kinase activation by using Ab microarrays

Signal transduction in mammalian cells is mediated by complex networks of interacting proteins. Understanding these networks at a circuit level requires devices to measure the amounts and activities of multiple proteins in a rapid and accurate manner. Ab microarrays have previously been applied to the quantification of labeled recombinant proteins and proteins in serum. The development of methods to analyze intracellular signaling molecules on microarrays would make Ab arrays widely useful in systems biology. Here we describe the fabrication of multiplex Ab arrays sensitive to the amounts and modification states of signal transduction proteins in crude cell lysates and the integration of these arrays with 96-well microtiter plate technology to create microarrays in microplates. We apply the Ab arrays to monitoring the activation, uptake, and signaling of ErbB receptor tyrosine kinases in human tumor cell lines. Data obtained from multicolor ratiometric microarrays correlate well with data obtained by using traditional approaches, but the arrays are faster and simpler to use. The integration of microplate and microarray methods for crude cell lysates should make it possible to identify and analyze small molecule inhibitors of signal transduction processes with unprecedented speed and precision. We demonstrate the future potential of this approach by characterizing the action of the epidermal growth factor receptor inhibitor PD153035 on cells by using Ab arrays; direct scale-up to array-based screening in 96- and 384-well plates should allow small molecules to be identified with specific inhibitory profiles against a signaling network.     

Employment status at time of first hospitalization for heart failure is associated with a higher risk of death and rehospitalization for heart failure

Aims

Employment status at time of first heart failure (HF) hospitalization may be an indicator of both self‐perceived and objective health status. In this study, we examined the association between employment status and the risk of all‐cause mortality and recurrent HF hospitalization in a nationwide cohort of patients with HF.

Methods and results

We identified all patients of working age (18–60 years) with a first HF hospitalization in the period 1997–2015 in Denmark, categorized according to whether or not they were part of the workforce at time of the index admission. The primary outcome was death from any cause and the secondary outcome was readmission for HF. Cumulative incidence curves, binomial regression and Cox regression models were used to assess outcomes. Of 25 571 patients with a first hospitalization for HF, 15 428 (60%) were part of the workforce at baseline. Patients in the workforce were significantly younger (53 vs. 55 years) more likely to be male (75% vs 64%) and less likely to have diabetes (13% vs 22%) and chronic obstructive pulmonary disease (5% vs 10%) (all P < 0.0001). Not being part of the workforce was associated with a significantly higher risk of death [hazard ratio (HR) 1.59; 95% confidence interval (CI) 1.50–1.68] and rehospitalization for HF (HR 1.09; 95% CI 1.05–1.14), in analyses adjusted for age, sex, co‐morbidities, education level, calendar time, and duration of first HF hospitalization.

Conclusion

Not being part of the workforce at time of first HF hospitalization was independently associated with increased mortality and recurrent HF hospitalization.

     

Serum levels of YKL-40 and PIIINP as prognostic markers in patients with alcoholic liver disease

BACKGROUND/AIMS: YKL-40 (growth factor) and PIIINP (N-terminal propeptide of Type III procollagen) are potential markers of liver fibrosis. The aim was to evaluate the prognostic value of serum YKL-40 and PIIINP levels in patients with alcoholic liver disease. METHODS: Three hundred and seventy patients with alcoholic liver disease were studied in a trial of malotilate with a median follow-up period of 470 days; 75 patients died; 336 patients had a liver biopsy on entry. Serum levels of YKL-40 and PIIINP were determined by radioimmunoassay (RIA). RESULTS: Serum YKL-40 and PIIINP were elevated in the patients compared to controls. Patients with steatosis or no fibrosis had the lowest serum levels of YKL-40 and PIIINP, whereas patients with alcoholic hepatitis and/or cirrhosis had the highest levels. Serum YKL-40 was associated with the presence of fibrosis, and serum PIIINP was also associated with the different grades of fibrosis. Patients with elevated serum YKL-40 or PIIINP had shorter survival than patients with normal serum levels of YKL-40 (P<0.0001) or PIIINP (P=0.044). High degree of fibrosis predicted shorter survival (P=0.004). CONCLUSIONS: Serum levels of YKL-40 and PIIINP are elevated in alcoholic patients, related to the presence of liver fibrosis and may provide prognostic information.