The Correlation between Methadone Dosages among Pairs of Heroin Users in Romantic Relationships and among Pairs of Heroin Users Who Are Siblings

This study explores whether an individual’s methadone dose is influenced by the level of another individual’s dose as a function of their relationship. Thirty-four subjects were recruited in this study; 16 subjects were in a partner relationship and 18 subjects were siblings. Multiple regression analysis revealed that the dose of one member of the dyad was a predictor of the dose of the other member of the dyad. Mean difference in dose was negatively associated with the correlation coefficient in sibling dyads but not partner dyads. Analysis of the dose curves showed that all partner dyads demonstrated a “collinearity pattern” or “coexistence pattern,” but a “distinct trend pattern” was only noted in sibling dyads. Our results suggest that there is a relationship between the methadone doses of members of a dyad and that this phenomenon is more remarkable in partnership dyads than sibling dyads.     

Nucleos(t)ide analogues for hepatitis B virus: Strategies for long-term success

Nucleoside and nucleotide analogues are potent HBV suppressors, but these agents rarely eradicate HBV. Therefore, the durability of viral response is a problem, and long-term therapy is usually required to ensure maintained HBV suppression. Studies have shown that long-term therapy starting with lamivudine may significantly improve survival, reduce the risk of liver-related major complications, and prevent the development of cirrhosis and HCC in chronic hepatitis B patients. However, drug resistance is a critical challenge during long-term nucleos(t)ide analogue maintenance therapy. The emergence of these mutants is characterized by an increasing level of serum HBV DNA, elevation of ALT level, and even hepatitis flare or decompensation. The prevention and proper management of drug resistance are crucial to ensure long-term success. To start treatment in the right patients at the right time with the right drug is essential in minimizing the problem of drug resistance. Each of these agents has a different profile of resistant mutations. In choosing a direct antiviral agent to initiate therapy, resistance profile is a crucial factor to consider, apart from potency and cost. In the case of drug resistance emerging, timely institution of a drug without cross-resistance may rescue the adverse effects of drug resistance and ensure the long-term success of nucleos(t)ide analogue therapy. To develop strategies for enhancing the therapeutic response and shortening the duration of therapy is an ultimate goal to avoid the problems of drug resistance.⁶⁸

• nucleos(t)ide analogues for hepatitis B virus (HBV) are highly effective in suppressing HBV replication but rarely eliminate the virus

• long-term therapy is usually required

• emergence of drug-resistant HBV mutations is a critical challenge

• to treat the right patient at the right time with the drug with highest genetic barrier to drug resistance is essential to minimize the problem with drug resistance

• the strategy of on-treatment adjustment based on level of suppression of HBV DNA needs to be clarified

• studies are needed to find the optimal combination therapy for both better therapeutic efficacy and less drug resistance

• oral antiviral agents able to attack cccDNA are urgently needed

CDw60 glycolipid antigens of human leukocytes: structural characterization and cellular distribution

Monoclonal CDw60 antibodies recognize glycolipid antigens with restricted surface expression on human leukocytes. They allow us to define new functional subpopulations of T lymphocytes and are able to induce costimulatory signals. In this report, we describe the molecular composition of CDw60 glycolipid antigens derived from different human leukocyte subpopulations. The glycolipids were isolated and their structures were identified by immunochemical methods. All molecules containing the CDw60 determinant were found in the disialoganglioside fraction. They were O-acetylated derivatives of the gangliosides II3 (Neu5Ac)2-LacCer (GD3), IV3 (Neu5Ac)2-nLc4Cer (DSPG), and VI3 (Neu5Ac)2- nLc6Cer (DSnHC), respectively. The most common CDw60 glycolipid antigen in human leukocytes was 9-O-acetyl GD3. In a comparison of various cell types, the highest concentration of 9-O-acetyl GD3 on a per cell basis was determined in granulocytes and in blood T lymphocytes, whereas B lymphocytes, thymus cells, and monocytes contained considerably smaller amounts of this molecule. Polar CDw60 antigens such as 9-O-acetyl DSPG and 9-O-acetyl DSnHC were only detected in granulocytes.     

Non-apnea sleep disorder and its risk for all kinds of injuries: A 14-year follow-up for a nationwide population-based retrospective study

Non-apnea sleep disorder (NASD) increases the risk of motor vehicle accidents. However, systemic review of NASD and its risk for all causes of injury is lacking. The aim of the present study was to provide a detailed demographic data on NASD and all causes of injury in a 14-year follow up.Our study utilized outpatient and inpatient data from the Longitudinal Health Insurance Database between 2000 and 2013 in Taiwan. We enrolled 989,753 individuals aged ≥20 years who were diagnosed with NASD as outpatients ≥3 times or inpatients ≥1 time. We matched the study cohort with a comparison cohort by age, index date and comorbidities at a ratio of 1:4. We used Cox proportional hazards regression to analyze the association of NASD and the cause of injury.In this 14-year follow up study, patients with NASD had 12.96% increased risk of injury compared to that of the control cohort. Fall was the first place of the cause of injury with 670.26 per 10⁵ PYs. In the stratified age group, patients aged ≧65 years had the highest risk of injury (adjusted HR= 1.381; P < .001). Kaplan–Meier analysis showed that the incidence of injury between the with- and without-NASD cohorts started from the first year and persisted until the end of the follow-up.Our study demonstrates that NASD patients were associated with higher risk of all causes of injuries, with falling being the most prevalent diagnosis. The general public should be more aware of this neglected issue of NASD.     

Effects of diallyl trisulfide on induction of apoptotic death in murine leukemia WEHI‐3 cells in vitro and alterations of the immune responses in normal and leukemic mice in vivo

Diallyl trisulfide (DATS), a chemopreventive dietary constituent and extracted from garlic, has been shown to against cultured many types of human cancer cell liens but the fate of apoptosis in murine leukemia cells in vitro and immune responses in leukemic mice remain elusive. Herein, we clarified the actions of DATS on growth inhibition of murine leukemia WEHI‐3 cells in vitro and used WEHI‐3 cells to generate leukemic mice in vivo, following to investigate the effects of DATS in animal model. In in vitro study, DATS induced apoptosis of WEHI‐3 cells through the G0/G1 phase arrest and induction of caspase‐3 activation. In in vivo study DATS decreased the weight of spleen of leukemia mice but did not affect the spleen weight of normal mice. DATS promoted the immune responses such as promotions of the macrophage phagocytosis and NK cell activities in WEHI‐3 leukemic and normal mice. However, DATS only promotes NK cell activities in normal mice. DATS increases the surface markers of CD11b and Mac‐3 in leukemia mice but only promoted CD3 in normal mice. In conclusion, the present study indicates that DATS induces cell death through induction of apoptosis in mice leukemia WHEI‐3 cells. DATS also promotes immune responses in leukemia and normal mice in vivo. © 2014 Wiley Periodicals, Inc. Environ Toxicol 30: 1343–1353, 2015.