Baseline and on-treatment HBcrAg levels as predictors of HBeAg seroconversion in chronic hepatitis B patients treated with antivirals.

HBeAg seroconversion is an important treatment endpoint. We aimed to identify predictors of seroconversion using serum HBsAg and hepatitis B core-related antigen (HBcrAg) in HBeAg-positive patients treated with nucleos(t)ide analogs (NAs). Data and samples from 70 HBeAg-positive patients treated with entecavir or tenofovir between January 2007 and December 2017 were retrospectively analysed. The mean follow-up period was 11 years. The predictive power for HBeAg seroconversion of HBcrAg levels at baseline and 2 years after antiviral therapy was determined using receiver operating curve analysis. Twenty-one patients (30%) achieved HBeAg seroconversion at a mean of 28 (range, 12-84) months after antiviral treatment. The median baseline HBcrAg and HBsAg levels were 6.9(5.7-7.0) vs. 5.8(5.5-6.5) log10 U/mL (p = .006), 4.9(4.5-5.1) vs. 4.5(4.1-5.0) log10 IU/mL (p = .044) in the no seroconversion group and seroconversion group, respectively. In the multivariate analysis, the serum HBcrAg levels at baseline and 2 years after antiviral therapy were predictive factors for HBeAg seroconversion ([HR]; 0.326; [CI], 0.111-0.958; p = .042 and HR, 0.4555; CI, 0.211-0.984; p = .045). HBcrAg levels≤6.5log10 U/mL at baseline and ≤5.3log10 U/mL at 2 years after antiviral therapy had sensitivities of 53.1% and 69.8%, specificities of 95.2% and 70.6%, positive predictive values of 82.6% and 50.0%, and negative predictive values of 82.6% and 84.5%, respectively, with AUROCs of 0.712 (95%CI, 0.596-0.830) and 0.745 (95%CI, 0.599-0.891) for predicting HBeAg seroconversion. In chronic hepatitis B patients treated with NAs, HBcrAg levels≤6.5log10 U/mL at baseline and ≤5.3log10 U/mL at 2 years after antiviral therapy were useful predictive factors of HBeAg seroconversion.

The effect of a multispecies probiotic mixture on the symptoms and fecal microbiota in diarrhea-dominant irritable bowel syndrome: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: The clinical effect of probiotics on irritable bowel syndrome (IBS) is still controversial. AIMS: We aimed to evaluate the effects of a probiotic mixture on IBS symptoms and the composition of fecal microbiota in patients with diarrhea-dominant IBS (D-IBS). METHODS: Fifty patients with D-IBS were randomized into placebo or probiotic mixture (Lactobacillus acidophilus, Lactobacillus plantarum, Lactobacillus rhamnosus, Bifidobacterium breve, Bifidobacterium lactis, Bifidobacterium longum, and Streptococcus thermophilus 1.0×10 CFU) groups. Treatment was taken daily for 8 weeks. The primary outcome was adequate relief (AR) of overall IBS symptoms, which was assessed weekly for 10 weeks. A responder was defined as a patient who experienced AR for at least half of the 10-week study period. Secondary outcomes included the effects on individual symptoms, stool parameters, and IBS quality of life. The fecal flora compositions were analyzed by polymerase chain reaction denaturing gradient gel electrophoresis (DGGE). RESULTS: The proportion of AR was consistently higher in the probiotics group than in the placebo group throughout the 10-week period (P<0.05). The proportion of responders was significantly higher in the probiotics group than in the placebo group (48% vs. 12%, P=0.01). Stool consistency improved significantly in the probiotics group compared with the placebo group. Percent changes in individual symptom scores were similar in the 2 groups, but IBS quality of life improvement tended to be higher in the probiotics group. Comparison of denaturing gradient gel electrophoresis profiles of fecal flora showed that the concordance rate between bacterial compositions before and after treatment was significantly higher in the probiotics group than in the placebo group (69.5% vs. 56.5%, P=0.005). CONCLUSIONS: The probiotic mixture was effective in providing AR of overall IBS symptoms and improvement of stool consistency in D-IBS patients, although it had no significant effect on individual symptoms. The therapeutic effect of probiotics is associated with the stabilization of intestinal microbiota.

Transcriptional regulatory networks underlying the reprogramming of spermatogonial stem cells to multipotent stem cells.

Spermatogonial stem cells (SSCs) are germline stem cells located along the basement membrane of seminiferous tubules in testes. Recently, SSCs were shown to be reprogrammed into multipotent SSCs (mSSCs). However, both the key factors and biological networks underlying this reprogramming remain elusive. Here, we present transcriptional regulatory networks (TRNs) that control cellular processes related to the SSC-to-mSSC reprogramming. Previously, we established intermediate SSCs (iSSCs) undergoing the transition to mSSCs and generated gene expression profiles of SSCs, iSSCs and mSSCs. By comparing these profiles, we identified 2643 genes that were up-regulated during the reprogramming process and 15 key transcription factors (TFs) that regulate these genes. Using the TF-target relationships, we developed TRNs describing how these TFs regulate three pluripotency-related processes (cell proliferation, stem cell maintenance and epigenetic regulation) during the reprogramming. The TRNs showed that 4 of the 15 TFs (Oct4/Pou5f1, Cux1, Zfp143 and E2f4) regulated cell proliferation during the early stages of reprogramming, whereas 11 TFs (Oct4/Pou5f1, Foxm1, Cux1, Zfp143, Trp53, E2f4, Esrrb, Nfyb, Nanog, Sox2 and Klf4) regulated the three pluripotency-related processes during the late stages of reprogramming. Our TRNs provide a model for the temporally coordinated transcriptional regulation of pluripotency-related processes during the SSC-to-mSSC reprogramming, which can be further tested in detailed functional studies.

When do persuasive messages on vaccine safety steer COVID-19 vaccine acceptance and recommendations? Behavioral insights from a randomised controlled experiment in Malaysia.

IntroductionVaccine safety is a primary concern among vaccine hesitant individuals. We examined how seven persuasive messages with different frames, all focusing on vaccine safety, influenced Malaysians to accept the COVID-19 vaccine, and recommend it to individuals with different health and age profiles; i.e. healthy adults, elderly, and people with pre-existing health conditions. MethodsA randomized controlled experiment was conducted among 5,784 Malaysians who were randomly allocated into 14 experimental arms. They were exposed to one or two messages that promoted COVID-19 vaccination. Interventional messages were applied alone or in combination and compared against a control message. Outcome measures were assessed as intent to both take the vaccine and recommend it to healthy adults, elderly, and people with pre-existing health conditions, before and after message exposure. Changes in intent after message exposure were modeled and we estimate the average marginal effects with respect to changes in the predicted probability of selecting a positive intent for all four outcomes. ResultsThe average baseline proportion of participants with positive intents in each arm to take, and recommend the vaccine to healthy adults, elderly, and people with pre-existing health conditions was 61.6%, 84.9%, 72.7% and 51.4% respectively. We found that persuasive communication via several of the experimented messages improved recommendation intent to people with pre-existing health conditions, with improvements ranging between 4 to 8 percentage points. In contrast, none of the messages neither significantly improved vaccination intentions, nor recommendations to healthy adults and the elderly. Instead, we found evidence suggestive of backfiring among this group with messages using negative frames, risky choice frames, and priming descriptive norms. ConclusionPersuasive messages aimed at influencing vaccination decisions should incorporate a combination of factors linked to hesitancy. Messages intended to promote recommendation of novel health interventions to people with pre-existing health conditions should incorporate safety dimensions. Clinical Trials registration numberNCT05244356 Key Messages1. What is already known?O_LIPersuasive messages have been shown to influence COVID-19 vaccination intentions, but evidence from Low- and Middle-income countries are limited. C_LIO_LIThere are limited studies investigating the effect of persuasive messages in influencing decisions to recommend the COVID-19 vaccine, with only a single study to date which investigated effects directed at recommending the COVID-19 vaccine to a friend, but without considering the individuals health and age profile. C_LI 2. What are the new findings?O_LIPersuasive messages that focused on vaccine safety did not positively influence Malaysian adults to take the COVID-19 vaccine or recommend it to healthy adults and the elderly, while messages framed as descriptive norms, negative attribute, and risky choices, significantly backfired for some of these outcomes. C_LIO_LISeveral persuasive messages focusing on vaccine safety significantly improved intent to recommend the COVID-19 vaccine to people with pre-existing health conditions. C_LI 3. What do the new findings imply?O_LIInstead of only addressing safety, persuasive messages aimed at nudging vaccination should incorporate multiple behavioral determinants linked to vaccine acceptance. C_LIO_LIPersuasive messages that are intended to promote uptake of novel health interventions should incorporate safety dimensions as a form of assurance for others to recommend it to people with pre-existing health conditions, given that they may be perceived as more susceptible to hazards from adverse events. C_LI