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Cardiac ventricular myocytes possess an extensive t-tubular system that facilitates the propagation of membrane potential across the cell body. It is well established that ionic currents at the restricted t-tubular space may lead to significant changes in ion concentrations, which, in turn, may affect t-tubular membrane potential. In this study, we used the whole cell patch-clamp technique to study accumulation and depletion of t-tubular potassium by measuring inward rectifier potassium tail currents (IK1,tail), and inward rectifier potassium current (IK1) "inactivation". At room temperatures and in the absence of Mg2+ ions in pipette solution, the amplitude of IK1,tail measured ~10 min after the establishment of whole cell configuration was reduced by ~18%, but declined nearly twofold in the presence of 1 mM cyanide. At ~35°C IK1,tail was essentially preserved in intact cells, but its amplitude declined by ~85% within 5 min of cell dialysis, even in the absence of cyanide. Intracellular Mg2+ ions played protective role at all temperatures. Decline of IK1,tail was accompanied by characteristic changes in its kinetics, as well as by changes in the kinetics of IK1 inactivation, a marker of depletion of t-tubular K+. The data point to remodeling of t tubules as the primary reason for the observed effects. Consistent with this, detubulation of myocytes using formamide-induced osmotic stress significantly reduced IK1,tail, as well as the inactivation of inward IK1. Overall, the data provide strong evidence that changes in t tubule volume/structure may occur on a short time scale in response to various types of stress. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) is a major complication of diabetes mellitus (DM). Inflammation is an essential component in the process of CKD progression in patients with DM. Diet is a significant determinant of systemic inflammation levels. However, the association between the dietary inflammatory index (DII) and CKD in individuals with DM remains largely unknown; therefore, the aim of this study was to explore whether the DII is linked to the prevalence of CKD in patients with DM. The research method was as follows: first, data from the National Health and Nutrition Examination Survey (NHANES) between 1999 and 2018 were obtained. There were 7,974 participants in our study. These individuals were then classified into three groups according to DII tertiles (T1-T3), with each group consisting of 2,658 participants. Logistic regression analysis was employed to examine whether there was a connection between the DII and CKD. We observed a significant association between the DII and the prevalence of CKD in individuals with DM. After full adjustment for age, sex, ethnicity, smoking, drinking, body mass index (BMI), triglyceride (TG), total cholesterol (TC), metabolic equivalents (METs), energy intake, hypoglycemic medications, hypertension, and cardiovascular disease (CVD), the group with a higher DII had a greater frequency of CKD (T2 group: OR: 1.40; 95% CI: 1.10-1.76; p = 0.006; T3 group: OR: 1.67; 95% CI: 1.29-2.17; p < 0.001). The implementation of an anti-inflammatory diet could serve as an intervention strategy for patients with DM to prevent the onset of CKD. [ABSTRACT FROM AUTHOR]

• Live, attenuated and inactivated hepatitis A vaccines are both immunogenic and show long-term duration of protection. • Live, attenuated and inactivated hepatitis A vaccines have similar per-dose safety profiles. • Use of either vaccine results in similar population immunity and low incidence of hepatitis A. In 2008, China introduced live, attenuated hepatitis A vaccine (L-HepA, licensed in 1992) and inactivated hepatitis A vaccine (I-HepA, licensed in 2002) nationwide, and is currently the only country using L-HepA in routine immunization. We assessed seropositivity and its duration following vaccination, safety, and association with hepatitis A incidence and population seroprevalence for I-HepA and L-HepA. We obtained seroprevalence data from two nationwide serosurveys (in 1992 and 2014), vaccination status from the 2014 serosurvey, and vaccine safety and disease incidence data from the national surveillance system. We compared long-term HAV seropositivity among vaccine recipients and described safety profiles of both vaccines. We categorized the 31 provinces into those predominately using I-HepA and achieving high coverage (n = 4), those predominately using L-HepA achieving high coverage (n = 4), and those predominately using L-HepA achieving lower coverage (n = 23). We compared population HAV seropositivity, coverage, and disease incidence among the three groups. One year after vaccination, seropositivity from I-HepA was significantly higher than from L-HepA (97.8% vs 90.7%), and seropositivity declined to 73.5% for L-HepA and 75.4% for I-HepA after 10 years – not significantly different by vaccine. The annual incidence of serious AEFI was <0.5/100 000 for both vaccines. Prior to licensure of either HepA vaccine, provinces that would go on to predominantly use I-HepA had lower incidences of hepatitis A and lower seropositivity levels to HAV than provinces that would go on to use L-HepA. By 2014, these differences were significantly diminished. Regardless of vaccine selection, all three province groups had lower immunity to HAV among individuals born during the 10 years prior to nationwide vaccine introduction – individuals who were 10 to 24 years old in 2014. Evidence of good immunogenicity, safety, and impact on incidence supports continued use of both I-HepA and L-HepA in the EPI system. These results may be useful for countries considering integrating HepA vaccines into their routine programs. [ABSTRACT FROM AUTHOR]

Background: Hepatitis B vaccine is an effective measure to prevent hepatitis B virus infection. Whether chronic hepatitis C virus (HCV) infection decreases humoral and cell-mediated immunity responses to hepatitis B vaccination is still controversial.Methods: Patients with chronic HCV infection who were not in treatment and healthy controls, matched at a 1:2 ratio for community, sex, and age (within 5 years), were identified from a community-based screening. All participants received 3 doses of hepatitis B vaccine. Antibody to hepatitis B surface antigen was tested 1 month after the third vaccine dose and was compared between 2 groups. Spot-forming cells (SFCs) of interferon γ and interleukin 2, 4, 5, and 6 were counted by means of enzyme-linked immunospot, and SFC counts were compared between the 2 groups.Results: The rates of nonresponse and low, normal, and high response were 3.80%, 10.13%, 45.57%, and 40.50% respectively, in the HCV group, and the corresponding rates in the healthy control group were 1.26%, 10.13%, 39.24%, and 49.37% (all P > .05). There were no significant differences in SFC counts between the 2 groups for interferon γ or interleukin 2, 4, or 5 (all P > .05).Conclusions: This study provided preliminary evidence of the good immunogenicity and safety of hepatitis B vaccination among patients in China with chronic hepatitis C who are not in treatment.Clinical Trials Registration: NCT 02898922. [ABSTRACT FROM AUTHOR]

China's hepatitis B virus (HBV) prevention policy has been evaluated through nationally representative serologic surveys conducted in 1992 and 2006. We report results of a 2014 serologic survey and reanalysis of the 1992 and 2006 surveys in the context of program policy. The 2014 survey used a 2-stage sample strategy in which townships were selected from 160 longstanding, nationally representative, county-level disease surveillance points, and persons 1-29 years of age were invited to participate. The 2014 sample size was 31,713; the response rate was 83.3%. Compared with the 1992 pre-recombinant vaccine survey, HBV surface antigen prevalence declined 46% by 2006 and by 52% by 2014. Among children <5 years of age, the decline was 97%. China's HBV prevention program, targeted toward interrupting perinatal transmission, has been highly successful and increasingly effective. However, this progress must be sustained for decades to come, and elimination of HBV transmission will require augmented strategies. [ABSTRACT FROM AUTHOR]

Background: China reduced hepatitis B virus (HBV) infection by 90% among children under 5 years old with safe and effective hepatitis B vaccines (HepB). In December 2013, this success was threatened by widespread media reports of infant deaths following HepB administration. Seventeen deaths and one case of anaphylactic shock following HBV vaccination had been reported.Methods: We conducted a telephone survey to measure parental confidence in HepB in eleven provinces at four points in time; reviewed maternal HBV status and use of HepB for newborns in birth hospitals in eight provinces before and after the event; and monitored coverage with hepatitis B vaccine and other programme vaccines in ten provinces.Results: HepB from the implicated company was suspended during the investigation, which showed that the deaths were not caused by HepB vaccination. Before the event, 85% respondents regarded domestic vaccines as safe, decreasing to 26.7% during the event. During the height of the crisis, 30% of parents reported being hesitant to vaccinate and 18.4% reported they would refuse HepB. Use of HepB in the monitored provinces decreased by 18.6%, from 53 653 doses the week before the event to 43 688 doses during the week that Biokangtai HepB was suspended. Use of HepB within the first day of life decreased by 10% among infants born to HBsAg-negative mothers, and by 6% among infants born to HBsAg-positive mothers. Vaccine refusal and HepB birth dose rates returned to baseline within 2 months; confidence increased, but remained below baseline.Conclusions: The HBV vaccine event resulted in the suspension of a safe vaccine, which was associated with a decline of parental confidence, and refusal of vaccination. Suspension of a vaccine can lead to loss of confidence that is difficult to recover. Timely and credible investigation, accompanied by proactive outreach to stakeholders and the media, may help mitigate negative impact of future coincidental adverse events following immunization. [ABSTRACT FROM AUTHOR]

Background. Endemic hepatitis B virus (HBV) infection is a serious health problem in China. Hepatitis B vaccination of infants was introduced in 1992 and was progressively expanded during the subsequent 15 years. Methods. We conducted a national serosurvey, with participants selected by multiple-stage random sampling. Demographic characteristics and hepatitis B vaccination history were collected by a questionnaire and a review of vaccination records, and serum specimens were tested for hepatitis B surface antigen, antibody to hepatitis B core antigen, and hepatitis B surface antibody by enzyme-linked immunosorbent assay. Results. Hepatitis B vaccine coverage (3 doses) increased from 30.0% for children born in 1992 to 93.4% for children born in 2005. Receipt of a timely birth dose increased from 22.2% to 82.6% for children born during this interval. Multivariate analysis showed that older age, western and rural residence, birth at home, and certain ethnicities were risk factors for undervaccination with both full vaccine series and timely birth dose. The prevalence of hepatitis B surface antigen was reduced to 2.1% among all children and 1.0% among children born after 1999. The efficacy of hepatitis B vaccination with a timely birth dose was 88.3%. Conclusions. Hepatitis B vaccine has been successfully integrated into routine infant immunization in China, now reaching most infants within 24 h after birth, and the prevalence of hepatitis B surface antigen has been greatly reduced among children born after 1992. [ABSTRACT FROM AUTHOR]

The China GAVI Project (CGP) was initiated in 2002 to provide hepatitis B (HB) vaccine to infants born in the less developed areas of China including the Western provinces and poverty counties of Middle provinces, to prevent the consequences of hepatitis B virus infection. By 2009, the project areas had raised coverage of 3 doses of HB vaccine and timely birth doses to almost 90% among infants, comparable to those in wealthier Eastern provinces, and reduced HBV prevalence to <1% among children in these areas. We estimated the impact in disease prevented by HB vaccine in China between 1992, when the vaccine was routinely recommended, and 2009, and in CGP areas for the years 2003–2009, when the CGP was active. A published model was used to estimate the burden of chronic and acute HBV infection and death prevented due to HB vaccination in China and the CGP areas using data from national serosurveys in China in 1992 and 2006, and HB vaccine coverage from surveys in 2004, 2006 and 2010. We used sigmoid modeling to estimate vaccine coverage nationally, regionally, and CGP areas. We also estimated the incremental impact of the CGP on HB vaccine coverage in those underserved areas. Our findings suggest that between 1992 and 2009, HB vaccination in China has prevented 24 million chronic HBV infections and 4.3 million future deaths due to cirrhosis, hepatocellular carcinoma and acute hepatitis. During the CGP between 2003 and 2009, an estimated 3.8 million chronic HBV infections and 680,000 deaths were prevented in CGP areas. We found that the CGP funding increased HB vaccine coverage in project areas by 4–15% for HB3 and 4–27% for timely birth dose beyond the coverage expected without the CGP. The CGP represents a highly successful public health collaboration between the national government and international partners. [ABSTRACT FROM AUTHOR]