Risk of sarcopenia among older persons with Type 2 diabetes mellitus with different status of albuminuria: A dose-responsive association.

BACKGROUND: The association between type 2 diabetes mellitus (T2DM) and sarcopenia has been reported before, but little was known regarding associations between albuminuria status in the development of sarcopenia. This study aimed to explore the associations between albuminuria status and sarcopenia among older patients with T2DM. METHODS: This cross-sectional study recruited T2DM patients aged 65 years and older from the DM shared care center in a regional hospital who were grossly absent from functional impairment. Demographic characteristics were collected and functional assessments were performed for all participants. Urinary albumin-to-creatinine ratio (UACR) was obtained by spot urine exams, whereas UACR ≥ 30 mg/g was defined as microalbuminuria, and UACR > 300 mg/g as macroalbuminuria. Appendicular lean mass (ASM) was measured by the dual X-ray absorptiometry, and the relative appendicular muscle mass (RASM) was calculated as the ASM divided by height square (kg/m2).The definition of sarcopenia was made according to the Asian Working Group for Sarcopenia and muscle quality was defined as handgrip strength (kg) divided by RASM. RESULTS: Overall, 180 participants (mean age: 72.5±5.3 years, 53.3% males) were enrolled for study. Higher HbA1c levels and poorer renal function were significantly associated with more severe albuminuria status.Besides, sarcopenia and low handgrip strength also showed dose-responsive associations with albuminuria status, which was similar in muscle quality.The receiver operating characteristic curve determine that the UACR of 13.7 mg/g was the optimal cutoff for sarcopenia diagnosis, which was lower than the conventionally definition of microalbuminuria (<30 mg/g). CONCLUSIONS: Albuminuria status was dose-responsively associated with sarcopenia among older persons with T2DM, and the risk started to escalate from minimal albuminuria (UACR 9.18 mg/g in men and 18.4 mg/g in women). Further intervention studies are needed to evaluate potential benefits of better diabetes control in preventing sarcopenia and its outcomes.

Heparin at physiological concentration can enhance PEG-free in vitro infection with human hepatitis B virus.

Hepatitis B virus (HBV) is a blood-borne pathogen responsible for chronic hepatitis, cirrhosis, and liver cancer. The mechanism of HBV entry into hepatocytes remains to be investigated. Recently, sodium taurocholate cotransporting polypeptide (NTCP) was discovered as a major HBV receptor based on an in vitro infection system using NTCP-reconstituted HepG2 cells. However, this infection system relies on the compound polyethylene glycol (4% PEG), which is not physiologically relevant to human infection. High concentration of heparin has been commonly used as an inhibitor control for in vitro infection in the field. Surprisingly, we found that heparin at physiological concentration can enhance HBV infection in a PreS1-peptide sensitive, NTCP-dependent manner in both HepaRG and HepG2-NTCP-AS cells. O-sulfation of heparin is more important for the infection enhancement than N-sulfation. This system based on the HepG2-NTCP-AS cells can support in vitro infection with HBV genotypes B and C, as well as using serum samples from HBeAg positive and negative chronic carriers. In summary, our study provides a PEG-free infection system closely resembling human natural infection. In addition, it points to a future research direction for heparin and heparin-binding host factor(s) in the blood, which are potentially involved in viral entry. To our knowledge, this is the first soluble and circulatory host factor which can enhance HBV in vitro infection.

Lymphopenia and poor performance status as major predictors for infections among residents in long-term care facilities (LTCFs): a prospective cohort study.

The main aim of this study was to investigate the risk factors and consequence of LTCFs-acquired infections in Taiwan through a 16-month follow-up. This prospective cohort study invited residents of 10 private LTCFs in Taipei for study. For each participant, Karnofsky Performance Scale (KPS), use of feeding tube and/or urinary catheters, serum levels of albumin, total cholesterol, complete blood count, occurrence of LTCF-acquired infections, all-cause mortality were recorded. Overall, a total of 198 LTCF residents entered the study for a total of 67,395 resident-days, and 156 participants (79.8±9.7 years, 51.3% males) complete the follow-up with a total of 67,395 resident-days. During the study period, 360 LTCF-acquired infections occurred, and the incidence was estimated to be 5.34 episodes per 1000 resident-days. Subjects with LTCF-acquired infections were more likely to die than those without infections. Besides, subjects with lymphopenia and long-term use of feeding tube and/or urinary catheters were significant risk factors for LTCF-acquired infections. However, poorer functional status and occurrence of lower respiratory tract infections were significant predictive factors for all-cause mortality. In conclusion, the period prevalence of LTCF-acquired infections was higher in Taiwan than previous reports, but the incidence was similar. In addition to traditional risk factors, lymphopenia, a surrogate indicator for immunosenescence, was a significant risk factor for LTCF-acquired infections.

Ptenb mediates gastrulation cell movements via Cdc42/AKT1 in zebrafish.

Phosphatidylinositol 3-kinase (PI3 kinase) mediates gastrulation cell migration in zebrafish via its regulation of PIP(2)/PIP(3) balance. Although PI3 kinase counter enzyme PTEN has also been reported to be essential for gastrulation, its role in zebrafish gastrulation has been controversial due to the lack of gastrulation defects in pten-null mutants. To clarify this issue, we knocked down a pten isoform, ptenb by using anti-sense morpholino oligos (MOs) in zebrafish embryos and found that ptenb MOs inhibit convergent extension by affecting cell motility and protrusion during gastrulation. The ptenb MO-induced convergence defect could be rescued by a PI3-kinase inhibitor, LY294002 and by overexpressing dominant negative Cdc42. Overexpression of human constitutively active akt1 showed similar convergent extension defects in zebrafish embryos. We also observed a clear enhancement of actin polymerization in ptenb morphants under cofocal microscopy and in actin polymerization assay. These results suggest that Ptenb by antagonizing PI3 kinase and its downstream Akt1 and Cdc42 to regulate actin polymerization that is critical for proper cell motility and migration control during gastrulation in zebrafish.