Bismuth subsalicylate, probiotics, rifaximin and vaccines for the prevention of travelers' diarrhea: a systematic review and network meta-analysis.

Background: Bismuth subsalicylate (BSS), probiotics, rifaximin, and vaccines have been proposed as preventive modalities for patients with travelers' diarrhea (TD), but their comparative effectiveness for prevention has rarely been studied. We aimed to perform a systematic review and network meta-analysis to test whether one of these modalities is more effective than the others in reducing the incidence of TD. Methods: We searched Pubmed, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, and clinical registries from inception of the databases through 18 November 2023, without language restriction, for randomized controlled trials (RCTs) evaluating the efficacy of BSS, probiotics, rifaximin, and vaccines in preventing TD. The primary outcome was the incidence of TD and the safety outcome was the incidence of adverse events. The relative ratio (RR) was used to assess the effect of the modalities, and RR estimates between any two of the modalities were calculated and pooled using a frequentist network meta-analysis model. Results: Thirty-one studies (recruiting 10,879 participants) were included in the analysis. Sixteen were judged to have a low risk of bias. In the aggregate analysis, BSS and rifaximin were more effective than placebo and other treatment modalities, which was further confirmed in the individual analysis. The comparison between rifaximin and placebo achieved high confidence, while the comparisons between BSS and placebo, ETEC and probiotics, and rifaximin and vaccines achieved moderate confidence. BSS had a higher rate of adverse events compared with other treatments. Conclusion: Rifaximin had a relative lower TD incidence and lower adverse event rate, and the evidence was with moderate confidence. Systematic Review Registration: https://osf.io/dxab6, identifier.

Induction of immunogenic cell death effect of licoricidin in cervical cancer cells by enhancing endoplasmic reticulum stress-mediated high mobility group box 1 expression.

Licoricidin (LCD) is an activity compound of the roots of Glycyrrhiza uralensis, which has therapeutic efficacy, including anti-virus, anti-cancer, and enhanced immunity in Traditional Chinese Medicine. Herein, this study aimed to clarify the effect of LCD on cervical cancer cells. In the present study, we found that LCD significantly inhibited cell viability via inducing cell apoptosis and companies with cleaved-PARP protein expression and caspase-3/-9 activity. Cell viability was markedly reversed these effects by pan-caspase inhibitor Z-VAD-FMK treatment. Furthermore, we showed that LCD-induced ER (endoplasmic reticulum) stress triggers upregulating the protein level of GRP78 (Bip), CHOP, and IRE1α, and subsequently confirmed the mRNA level by quantitative real-time polymerase chain reaction. In addition, LCD exhibited the release of danger-associated molecular patterns from cervical cancer cells, such as the release of high-mobility group box 1 (HMGB1), secretion of ATP, and exposure of calreticulin (CRT) on the cell surface, which led to immunogenic cell death (ICD). These results provide a novel foundation that LCD induces ICD via triggering ER stress in human cervical cancer cells. LCD might be an ICD inducer of immunotherapy in progressive cervical cancer.

Effect of Repetitive Transcranial Magnetic Stimulation on Post-stroke Dysphagia: A Meta-analysis of Stimulation Frequency, Stimulation Site, and Timing of Outcome Measurement.

Dysphagia is one of the most frequent sequelae of stroke. It can result in various complications such as malnutrition, dehydration, aspiration pneumonia, and poor rehabilitation outcomes. Repetitive transcranial magnetic stimulation (rTMS) has been reported to improve dysphagia after a stroke; however, effective treatment protocols have not been established yet. We evaluated the effect of the following rTMS parameters on post-stroke dysphagia: stimulation frequency [high frequency (≥ 3 Hz) or low frequency (1 Hz)] and stimulation site (ipsilesional or contralesional mylohyoid cortex). Outcomes were measured immediately, at 3 weeks, and at 4 weeks after the rTMS session. The PubMed, SCOPUS, Embase, and Cochrane Library databases were systematically searched for relevant studies published between January 01, 1980, and December 13, 2021. Randomized controlled trials on the effects of rTMS on post-stroke dysphagia were included. Six studies were finally included in the analysis. The selected studies included 158 patients (rTMS group: 81 patients; sham group: 77 patients). Regarding the effect of high-frequency rTMS on the ipsilesional cortex, the standardized swallowing assessment (SSA) scores showed significant improvement after rTMS sessions immediately and at 4 weeks [immediate: P = 0.02, standard mean difference (SMD) = - 0.61, 95% confidence interval (CI) = - 1.14 to - 0.08; 4 weeks: P = 0.006, SMD = - 0.74, 95% CI = - 1.27 to - 0.21]; however, there was no significant reduction in the Penetration-Aspiration Scale (PAS) scores between the rTMS and sham groups (immediate: P = 0.43, SMD = 0.25, 95% CI = - 0.36, 0.86; 3 weeks: P = 0.39, SMD = 0.37, 95% CI = - 0.47 to 1.22). After low-frequency rTMS on the ipsilesional cortex, a significantly greater improvement in the SSA scores was found in the rTMS group than in the sham group, both immediately and at 4 weeks after rTMS sessions (immediate: P = 0.03, SMD = - 0.59, 95% CI = - 1.12 to - 0.06; 4 weeks: P = 0.001, SMD = - 0.92, 95% CI = - 1.48 to - 0.37). In addition, immediately after the rTMS sessions, the PAS scores were significantly reduced in the rTMS group than in the sham group (P = 0.047, SMD = - 0.60, 95% CI = - 1.19 to - 0.01). However, at 4 weeks after rTMS sessions, there was no significant reduction in the PAS scores in the rTMS group compared to the sham group (P = 0.48, SMD = - 0.19, 95% CI = - 0.71 to 0.33). Both high-frequency rTMS of the ipsilesional cortex and low-frequency rTMS of the contralesional cortex improved some measurements of the swallowing function in stroke patients immediately and at 4 weeks after treatment.

Impaired median nerve mobility in patients with carpal tunnel syndrome: a systematic review and meta-analysis.

OBJECTIVES: This systematic review and meta-analysis investigated the mobility of the median nerve (MN) in carpal tunnel syndrome (CTS) patients compared to healthy people. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline was followed and the electronic databases including PubMed, Scopus, EMBASE, and Cochrane Library were searched up to April 2022. All published observational studies comparing the excursion of MN between participants with and without CTS were included. The quality of research was assessed by the Newcastle-Ottawa Scale tool. The primary outcome was the excursion of the MN under dynamic examination, representing nerve mobility quantified by the standardized mean difference (SMD) for random effect meta-analysis. RESULTS: Fourteen studies were included in the qualitative review, and twelve entered the meta-analysis involving a total of 375 CTS patients and 296 healthy controls. The forest plot revealed that the mobility of the MN significantly decreased in the CTS group compared to the non-CTS control (SMD = -1.47, 95% CI: -1.91, -1.03, p < 0.001, heterogeneity 82%). In subgroup analysis, both transverse and longitudinal methods for nerve excursion showed less nerve mobility in CTS than in non-CTS. CONCLUSIONS: This meta-analysis showed that the patients with CTS exhibited less mobility of the MN than those without CTS, suggesting MN mobility as a potential CTS marker. KEY POINTS: • The patients with CTS revealed less mobility of the median nerve than those without CTS. • The mobility of the median nerve could be regarded as a potential CTS marker.

Ultrasonographic diagnosis and guided treatment of erector spinae aponeurosis enthesopathy.

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Effect of Perineural Injection with Different Dextrose Volumes on Median Nerve Size, Elasticity and Mobility in Hands with Carpal Tunnel Syndrome.

This study aimed to investigate the effect of different injectate volumes on ultrasonographic parameters and the correlation to clinical outcomes under perineural dextrose injection (PDI). In this post hoc analysis of the randomized, double-blinded, three-arm trial, ultrasound-guided PDI with either 1 mL, 2 mL, and 4 mL 5% dextrose water was administered, respectively, in 14, 14, and 17 patients. Ultrasound outcomes included mobility, shear-wave elastography (SWE), and cross-sectional area (CSA) of the median nerve; clinical outcomes were Visual Analog Scale (VAS) and Boston Carpal Tunnel Questionnaire (BCTQ) score. Outcomes were measured before injection, and after injection at the 1st, 4th, 12th, and 24th week. For ultrasound outcomes, CSA decreased significantly from baseline data at all follow-up time-points in the 2 mL group (p = 0.005) and the 4 mL group (p = 0.015). The mean change of mobility from baseline showed a greater improvement on the 4 mL group than the other groups at the 1st week post-injection. For clinical outcomes, negative correlation between the VAS and mobility at the 1st (p = 0.046) and 4th week (p = 0.031) post-injection in the 4 mL group were observed. In conclusion, PDI with higher volume yielded better nerve mobility and decreased CSA of median nerve, but no changes of nerve elasticity.

Identification of SUMO conjugation sites in the budding yeast proteome.

Post-translational modification by the small ubiquitin-like modifier (SUMO) is an important mechanism regulating protein function. Identification of SUMO conjugation sites on substrates is a challenging task. Here we employed a proteomic method to map SUMO acceptor lysines in budding yeast proteins. We report the identification of 257 lysine residues where SUMO is potentially attached. Amongst the hits, we identified already known SUMO substrates and sites, confirming the success of the approach. In addition, we tested several of the novel substrates using SUMO immunoprecipitation analysis and confirmed that the SUMO acceptor lysines identified in these proteins are indeed bona fide SUMOylation sites. We believe that the collection of SUMO sites presented here is an important resource for future functional studies of SUMOylation in yeast.

Evaluation of Taiwan's National Health Insurance policy: an importance-satisfaction analysis.

The hypothesis that policy performance affects citizens' satisfaction with public policies could be considered a well-worn topic. However, this paper shows that the extant literature has not adequately conceptualized nor addressed the relationship, which could exist between citizens' satisfaction and importance of the evaluation's indicators. The findings of most previous studies reflect elite perspectives on Taiwan's National Health Insurance (NHI) policy evaluation, and the importance of the evaluation's indicators may not be recognized by the public. In addition, previous satisfaction studies have not provided information on the level of evaluative indicator importance. This study utilized importance-satisfaction analysis to examine public preferences of the NHI policy and assigned weights for NHI policy evaluation indicators by administering a national phone survey in October 2009. A total of 1103 telephone interviews were conducted with people aged 20 years and older, comprising a sample that was representative of the Taiwanese population according to age, gender, and area of residence. Furthermore, to explore the difference between expected importance and perceived satisfaction, this study calculated a reconceptualized performance gap. To obtain the gap value for an indicator, the mean value for importance was subtracted from the mean value for satisfaction. The findings imply that public recognition and support constitute the premise for the successful operation and reform of the NHI policy. The study concludes that policy adjustment is needed in several areas where importance outweighed satisfaction, including access to medical care services and NHI efficiency. The results suggest public recognition of and satisfaction with the evaluation indicators in use and the need for policy adjustment in areas where importance outweighs satisfaction.

Metabolic flux network analysis of fermentative hydrogen production: using Clostridium tyrobutyricum as an example.

This study applies metabolic flux network analysis (MFA) to evaluate the metabolic flux of fermentative hydrogen production (FHP) with the use of Clostridium tyrobutyricum fed with either glucose or lactate/acetate as substrates. The MFA results suggest that hydraulic retention time (HRT) presents significant impact on hydrogen production from glucose. At HRT between 4 and 18 h, increase of HRT increased hydrogen production but decreased lactate production, while at HRT below 4 h decrease of HRT increased hydrogen production but decreased lactate production. The flux for lactate, butyrate and acetate seemed to affect H2 production, due presumably to their impacts on the balance of NADH, ferredoxin and ATP. It is suggested that the MFA can be a useful tool to provide valuable information for optimization and design of the fermentative hydrogen production process.

SUMOylation of the α-kleisin subunit of cohesin is required for DNA damage-induced cohesion.

BACKGROUND: Cohesion between sister chromatids is fundamental to ensure faithful chromosome segregation during mitosis and accurate repair of DNA damage postreplication. At the molecular level, cohesion establishment involves two defined events, a chromatin binding step and a chromatid entrapment event driven by posttranslational modifications on cohesin subunits. RESULTS: Here, we show that modification by the small ubiquitin-like protein (SUMO) is required for sister chromatid tethering after DNA damage. We find that all subunits of cohesin become SUMOylated upon exposure to DNA damaging agents or presence of a DNA double-strand break. We have mapped all lysine residues on cohesin's α-kleisin subunit Mcd1 (Scc1) where SUMO can conjugate. We demonstrate that Mcd1 SUMOylation-deficient alleles are still recruited to DSB-proximal regions but are defective in tethering sister chromatids and consequently fail to establish damage-induced cohesion both at DSBs and undamaged chromosomes. Moreover, we demonstrate that the bulk of Mcd1 SUMOylation in response to damage is carried out by the SUMO E3 ligase Nse2, a subunit of the related Smc5-Smc6 complex. SUMOylation occurs in cells with compromised Chk1 kinase activity, necessary for known posttranslational modifications on Mcd1, required for damage-induced cohesion. CONCLUSIONS: These findings demonstrate that SUMOylation of Mcd1 is a novel prerequisite for the establishment of DNA damage-induced cohesion at DSB-proximal regions and cohesion-associating regions (CARs) genome-wide.

The histone deacetylase Hos2 forms an Hsp42-dependent cytoplasmic granule in quiescent yeast cells.

One of many physiological adjustments in quiescent cells is spatial regulation of specific proteins and RNA important for the entry to or exit from the stationary phase. By examining the localization of epigenetic-related proteins in Saccharomyces cerevisiae, we observed the formation of a reversible cytosolic "stationary-phase granule" (SPG) by Hos2, a nuclear histone deacetylase. In the stationary phase, hos2 mutants display reduced viability. Additionally, they exhibit a significant delay when recovering from stationary phase. Hos2 SPGs also contained Hst2, a Sir2 homologue, and several stress-related proteins, including Set3, Yca1, Hsp26, Hsp42, and some known components of stress granules. However, Hos2 SPG formation does not depend on the formation of stress granules or processing bodies. The absence or presence of glucose is sufficient to trigger assembly or disassembly of Hos2 SPGs. Among the identified components of Hos2 SPGs, Hsp42 is the first and last member observed in the Hos2 SPG assembly and disassembly processes. Hsp42 is also vital for the relocalization of the other components to Hos2 SPGs, suggesting that Hsp42 plays a central role in spatial regulation of proteins in quiescent cells.

Intentional forgetting might be more effortful than remembering: an ERP study of item-method directed forgetting.

This study recorded ERPs while participants engaged in a procedure that combined semantic priming and item-method directed forgetting, aiming to investigate the issues of whether intentional forgetting demands cognitive efforts and modulates the semantic processing of to-be-remembered (TBR) and to-be-forgotten (TBF) items. Participants made lexical decisions to semantically related or unrelated prime and target words. A Remember/Forget cue, presented between the prime and target, designated the prime as TBR or TBF. When the cues were shown for 500 ms, targets preceded by Forget cues yielded a smaller P200 wave than those preceded by Remember cues. Furthermore, the topography of the N400 effect was different for targets preceded by Remember and Forget cues. The cues did not modulate the ERPs of the targets when they were shown for 1500 ms. Because P200 is sensitive to attention influence and the N400 effect reflects semantic processing, we conclude that forgetting is more effortful than remembering and that the semantic processing is different for TBR and TBF items. Nevertheless, there is a temporal limitation for the Remember/Forget cues to modulate the semantic processing and attentional resources in item-method directed forgetting.

Metabolic and energetic aspects of biohydrogen production of Clostridium tyrobutyricum: The effects of hydraulic retention time and peptone addition.

This study evaluates the microbial metabolism and energy demand in fermentative biohydrogen production using Clostridium tyrobutyricum FYa102 at different hydraulic retention times (HRT) over a period of 1-18 h. The hydrogen yield shows a positive correlation with the butyrate yield, the B/A ratio, and the Y(H2)/2(Y(HAc)+Y(HBu)) ratio, but a negative correlation with the lactate yield. A decrease in HRT, which is accompanied by an increased biomass growth, tends to decrease the B/A ratio, due presumably to a higher energy demand for microbial growth. The production of lactate at a low HRT, however, may involve an unfavorable change in e(-) equiv distribution to result in a reduced hydrogen production. Finally, the relatively high hydrogen yields observed in the bioreactor with the peptone addition may be ascribed to the utilization of peptone as an additional energy and/or amino-acid source, thus reducing the glucose demand for biomass growth during the hydrogen production process.

Microtubule damaging agents induce apoptosis in HL 60 cells and G2/M cell cycle arrest in HT 29 cells.

Microtubule damaging agents (such as paclitaxel and nocodazole (ND)) have been used in the clinical cancer chemotherapy. However, the molecular mechanisms of these agents in the induction of anti-cancer activity are still unclear. In the present study, we demonstrated that 0.2 microM podophyllotoxin (PDP) induced the occurrence of apoptosis in human leukemic (HL 60) cells and cell cycle arrest at the G2/M phase in HT 29 cells. Our results suggest that the PDP-induced G2/M arrest in HT 29 cells was through the intracellular events including (a) inhibition of normal mitotic spindle formation, (b) elevation of cyclin B1/cdc2 kinase activity, (c) concomitant increases in cdc 25 A phosphatase and cdk 7 kinase activity, and (d) down-regulation of the wee-1 protein expression. On the other hand, activations of the caspases 3, 8, and 9, Bcl-2 hyper-phosphorylation, and increased leakage of cytochrome c from mitochondria into cytosolic fraction were detected in the PDP-treated HL 60 cells. These listed intracellular events were interpreted to lead to the apoptosis observed in PDP-treated HL 60 cells. We further demonstrated that activation of c-jun N-terminal kinase (JNK) signaling pathway may play an important role in the PDP-induced Bcl-2 phosphorylation and apoptosis in HL 60 cells as evidenced by the JNK specific anti-sense oligonucleotide experiment. Our results demonstrated that the occurrence of apoptosis or G2/M cell cycle arrest induced by microtubule damaging agents in different cancer cells was through independent mechanisms. The results from the present study highlight the molecular mechanisms underlying of the PDP-induced anti-cancer activity.