Characterization of Tight Junctions and Their Disruption by UVB in Human Epidermis and Cultured Keratinocytes

It has not been confirmed whether tight junctions (TJs) function as a paracellular permeability barrier in adult human skin. To clarify this issue, we performed a TJ permeability assay using human skin obtained from abdominal plastic surgery. Occludin, a marker protein of TJs, was expressed in the granular layer, in which a subcutaneously injected paracellular tracer, Sulfo-NHS-LC-Biotin (556.59Da), was halted. Incubation with ochratoxin A decreased the expression of claudin-4, an integral membrane protein of TJs, and the diffusion of paracellular tracer was no longer prevented at the TJs. These results demonstrate that human epidermis possesses TJs that function as an intercellular permeability barrier at least against small molecules (∼550Da). UVB irradiation of human skin xenografts and human skin equivalents (HSEs) resulted in functional deterioration of TJs. Immunocytochemical staining of cultured keratinocytes showed that occludin was localized into dot-like shapes and formed a discontinuous network when exposed to UVB irradiation. Furthermore, UVB irradiation downregulated the active forms of Rac1 and atypical protein kinase C, suggesting that their inactivation caused functional deterioration of TJs. In conclusion, TJs function as a paracellular barrier against small molecules (∼550Da) in human epidermis and are functionally deteriorated by UVB irradiation

Estimating the immunogenicity of measles-rubella vaccination administered during a mass campaign in Lao People's Democratic Republic using multi-valent seroprevalence data.

Measles and rubella are important causes of morbidity and mortality globally. Despite high coverage reported for measles vaccination, outbreaks continue to occur in some countries. The reasons for these outbreaks are poorly understood. We apply Bayesian methods to multi-valent seroprevalence data for measles and rubella, collected 2 years and 3 months after a mass measles-rubella vaccination campaign in Lao PDR to estimate the immunogenicity and vaccination coverage. When the vaccination coverage was constrained to exceed 95% or 90%, consistent with officially-reported values, the immunogenicity of the measles vaccine component was unexpectedly low (75% (95% CR: 63-82%) and 79% (CR: 70-87%) respectively. The estimated immunogenicity increased after relaxing constraints on the vaccination coverage, with best-fitting values of 83% (95% CR: 73-91%) and 97% (95% CR: 90-100%) for the measles and rubella components respectively, with an estimated coverage of 83% (95% CR: 80-88%). The findings suggest that, if the vaccine coverage was as high as that reported, continuing measles outbreaks in Lao PDR, and potentially elsewhere, may be attributable to suboptimal immunogenicity attained in mass campaigns. Vaccine management in countries with high reported levels of coverage and ongoing measles outbreaks needs to be reviewed if measles elimination targets are to be achieved

Evaluation of nationwide supplementary immunization in Lao People's Democratic Republic: Population-based seroprevalence survey of anti-measles and anti-rubella IgG in children and adults, mathematical modelling and a stability testing of the vaccine.

BACKGROUND: Measles outbreaks have occurred in some countries despite supplementary immunization activities (SIA) using measles-containing vaccine with high vaccination coverage. We conducted a cross-sectional seroprevalence survey to estimate population immunity in Lao People's Democratic Republic where repeated mass immunization has failed to eliminate measles. METHODS AND FINDINGS: In this nationwide multistage cluster sampling survey conducted in 2014 based on probability proportionate to size sampling, blood samples were collected from 2,135 children and adults living in 52 randomly selected villages. Anti-measles and anti-rubella IgG were measured, and IgG prevalence was calculated. We applied mathematical modelling to estimate the number of cases of congenital rubella syndrome (CRS) in 2013 that were averted by the 2011 SIA. A stability testing was applied to the MR vaccine at 4°C, 25°C, and 35°C to examine stability differences between measles and rubella vaccine components. Measles IgG prevalence was significantly lower in the target age groups (5-21 years) of the 2011 SIA using a combination vaccine for measles and rubella vaccine (MR vaccine) than in young adults (22-39 years) (86.8% [95% CI: 83.0-90.6] vs. 99.0% [98.3-99.8]; p<0.001), whereas rubella IgG prevalence was significantly higher (88.2% [84.5-91.8] vs. 74.6% [70.7-78.5]; p<0.001). In the SIA target age groups, prevalence of measles IgG, but not rubella IgG, increased with age. CRS cases prevented in 2013 ranged from 16 [0-50] to 92 [32-180] if the force of infection had remained unchanged or had been reduced by 75%, respectively. In freeze-dried conditions, the measles vaccine component was more heat sensitive than the rubella component. CONCLUSIONS: Inconsistent IgG prevalence between measles and rubella in Lao PDR can be partly explained by different stability of the measles and rubella vaccine components under heat exposure. Suboptimal vaccine handling may cause insufficient immunogenicity for measles, which subsequently leads to an outbreak despite high SIA coverage, while direct evidence is lacking. Temperature monitoring of the vaccine should be conducted

Large Right Pulmonary Vein Is a Predictor of Atrial Fibrillation Recurrence after Pulmonary Vein Isolation in Patients with Persistent Atrial Fibrillation

Pulmonary vein isolation（PVI）is an effective treatment for atrial fibrillation（AF）. However, outcomes differ between paroxysmal AF and persistent AF. We analyzed the predictors of recurrence by examining the recurrence group after ablation. Of 372 consecutive patients with AF who underwent PVI between June 2016 and December 2018, we evaluated 250 patients（age, 67±12y, 65％ men）whose left atrium（LA）was constructed using the PENTARAY catheter（BioSense Webster, Los Angeles, CA）, a multipolar electrode catheter with a novel shape and excellent mapping capability. We measured the LA total volume（LATV）, right pulmonary vein＋antrum volume（RPAV）, left PV＋antrum volume（LPAV）, LA central volume（LACV）, and LA bipolar voltage. Of the 250 patients, 78 had persistent AF（recurrence, 20）and 172 had paroxysmal AF（recurrence, 16）. In all patients, LATV, LACV, RPAV, and LPAV were significantly larger in patients with persistent AF than those with paroxysmal AF. The mean LA bipolar voltage in patients with persistent AF was significantly lower than those with paroxysmal AF. In cases of persistent AF, RPAV was significantly larger in the recurrence group than that in the non-recurrence group（15.9±4.8 vs 13.4±5.4ml; P＜0.05）. In cases of paroxysmal AF, there were no differences in any volume between the recurrence and non-recurrence groups. In conclusion, larger right PV is a predictor of AF recurrence after PVI in patients with persistent AF. The right PV is close to the atrial septum and the septopulmonary bundle, and the expansion of RPAV reflects the disruption of these structures, which may be involved in this result

Comparison of population-based measles-rubella immunoglobulin G antibody prevalence between 2014 and 2019 in Lao People's Democratic Republic: Impacts of the national immunization program.

OBJECTIVES: We evaluated the effectiveness of the Lao People's Democratic Republic's measles-rubella immunization program using the seroprevalence from two cross-sectional surveys. METHODS: The nationwide surveys occurred in 2014 and 2019 using a multistage cluster sampling, both requiring samples from 2184 individuals from 52 randomly selected villages. Immunoglobulin G titers, measured using enzyme-linked immunosorbent assay, were considered positive at ≥120 mIU/ml (measles) and ≥10 IU/ml (rubella). We calculated the vaccination-related reduction in the force of rubella infection and the number of congenital rubella syndrome cases averted in 2019. RESULTS: We collected 2135 (women: 55.2%, mean age: 23.2 years) and 2001 (52.7%, 23.1 years) samples in 2014 and 2019, respectively. During 2014-2019, immunoglobulin G prevalence increased from 83.9% (95% confidence interval [CI]: 83.8-84.0) to 98.3% (97.7-98.8) for measles and from 75.4% (75.3-75.5) to 87.8% (86.4-89.2) for rubella. The most plausible reduction in the average force of rubella infection was 100% (95% CI: 28-100) since vaccination started, averting 78 (95% CI: 42-128) congenital rubella syndrome cases in 2019. CONCLUSION: This is the first population-based study for measles and rubella at two different time points in developing countries. Measles and rubella seroprevalence increased significantly during 2014-2019, greatly exceeding the immunity thresholds for their elimination

Symptomatic periesophageal vagal nerve injury by different energy sources during atrial fibrillation ablation

BackgroundSymptomatic gastric hypomotility (SGH) is a rare but major complication of atrial fibrillation (AF) ablation, but data on this are scarce.ObjectiveWe compared the clinical course of SGH occurring with different energy sources.MethodsThis multicenter study retrospectively collected the characteristics and clinical outcomes of patients with SGH after AF ablation.ResultsThe data of 93 patients (67.0 ± 11.2 years, 68 men, 52 paroxysmal AF) with SGH after AF ablation were collected from 23 cardiovascular centers. Left atrial (LA) ablation sets included pulmonary vein isolation (PVI) alone, a PVI plus a roof-line, and an LA posterior wall isolation in 42 (45.2%), 11 (11.8%), and 40 (43.0%) patients, respectively. LA ablation was performed by radiofrequency ablation, cryoballoon ablation, or both in 38 (40.8%), 38 (40.8%), and 17 (18.3%) patients, respectively. SGH diagnoses were confirmed at 2 (1–4) days post-procedure, and 28 (30.1%) patients required re-hospitalizations. Fasting was required in 81 (92.0%) patients for 4 (2.5–5) days; the total hospitalization duration was 11 [7–19.8] days. After conservative treatment, symptoms disappeared in 22.3% of patients at 1 month, 48.9% at 2 months, 57.6% at 3 months, 84.6% at 6 months, and 89.7% at 12 months, however, one patient required surgery after radiofrequency ablation. Symptoms persisted for &gt;1-year post-procedure in 7 patients. The outcomes were similar regardless of the energy source and LA lesion set.ConclusionsThe clinical course of SGH was similar regardless of the energy source. The diagnosis was often delayed, and most recovered within 6 months, yet could persist for over 1 year in 10%

Factors influencing basic vaccination coverage in Myanmar: secondary analysis of 2015 Myanmar demographic and health survey data

Abstract Background Immunization is one of the most effective measures for preventing disease when vaccination coverage is sufficient. Although vaccination coverage is known to be influenced by social and cultural barriers, the determinants of childhood immunization in Myanmar remain poorly understood. This study analyzed factors that influenced complete vaccination status (one dose each for Bacillus Calmette-Guérin and measles and three doses each for diphtheria-pertussis and polio) using 2015 data from the Myanmar Demographic Health and Survey. Methods Data from 12 to 23-month-old children and their mothers were extracted from the nationally representative survey results. Bivariate and multivariate analyses with survey-weighted logistic regression were performed to examine the relationships between vaccination status and various sociodemographic and medical factors. The independent variables for the analyses included area of residence, economic status, maternal age, marital status, education, literacy, employment status, antenatal care attendance, tetanus vaccination, place of delivery, postnatal evaluations, child’s sex, number of children, previous child death, decision maker(s) regarding child’s health, frequency of healthcare visits, paternal education, and paternal occupation. Results A representative sample of 904 cases were extracted for the analysis. The overall complete vaccination rate was 55.4%. In the multivariate analysis with backward step-wise selection, complete vaccination was independently associated with middle or high economic status (adjusted odds ratio [AOR]: 2.64, 95% confidence interval [CI]: 1.85–3.78), older maternal age (AOR: 2.87, 95% CI: 1.62–5.10), ≥4 antenatal care visits (AOR: 1.87, 95% CI: 1.28–2.73), and maternal tetanus vaccination before delivery (AOR: 3.26, 95% CI: 1.82–5.85). Conclusion The first Demographic and Health Survey in Myanmar revealed that only approximately one-half of 12–23-year-old children had received complete vaccination, which was lower than the estimated rate from routine administrative coverage. Our results indicate that incomplete immunization status was associated with low economic status, younger maternal age, fewer antenatal care visits, and no maternal tetanus vaccination. These findings may help improve the targeting and strategic implementation of the Expanded Programme on Immunization