NLRX1 Inhibits LPS-Induced Microglial Death via Inducing p62-Dependent HO-1 Expression, Inhibiting MLKL and Activating PARP-1.

The activation of microglia and the production of cytokines are key factors contributing to progressive neurodegeneration. Despite the well-recognized neuronal programmed cell death regulated by microglial activation, the death of microglia themselves is less investigated. Nucleotide-binding oligomerization domain, leucine-rich repeat-containing X1 (NLRX1) functions as a scaffolding protein and is involved in various central nervous system diseases. In this study, we used the SM826 microglial cells to understand the role of NLRX1 in lipopolysaccharide (LPS)-induced cell death. We found LPS-induced cell death is blocked by necrostatin-1 and zVAD. Meanwhile, LPS can activate poly (ADP-ribose) polymerase-1 (PARP-1) to reduce DNA damage and induce heme oxygenase (HO)-1 expression to counteract cell death. NLRX1 silencing and PARP-1 inhibition by olaparib enhance LPS-induced SM826 microglial cell death in an additive manner. Less PARylation and higher DNA damage are observed in NLRX1-silencing cells. Moreover, LPS-induced HO-1 gene and protein expression through the p62-Keap1-Nrf2 axis are attenuated by NLRX1 silencing. In addition, the Nrf2-mediated positive feedback regulation of p62 is accordingly reduced by NLRX1 silencing. Of note, NLRX1 silencing does not affect LPS-induced cellular reactive oxygen species (ROS) production but increases mixed lineage kinase domain-like pseudokinase (MLKL) activation and cell necroptosis. In addition, NLRX1 silencing blocks bafilomycin A1-induced PARP-1 activation. Taken together, for the first time, we demonstrate the role of NLRX1 in protecting microglia from LPS-induced cell death. The underlying protective mechanisms of NLRX1 include upregulating LPS-induced HO-1 expression via Nrf2-dependent p62 expression and downstream Keap1-Nrf2 axis, mediating PARP-1 activation for DNA repair via ROS- and autophagy-independent pathway, and reducing MLKL activation.

Identifying complementary and alternative medicine recommendations for anxiety treatment and care: a systematic review and critical assessment of comprehensive clinical practice guidelines.

Background: Clinical practice guidelines (CPGs) are used to guide decision-making, especially regarding complementary and alternative medicine (CAM) therapies that are unfamiliar to orthodox healthcare providers. This systematic review aimed to critically review and summarise CAM recommendations associated with anxiety management included in the existing CPGs. Methods: Seven databases, websites of six international guidelines developing institutions, and the National Centre for Complementary and Integrative Health website were systematically searched. Their reporting and methodological quality were evaluated using the Reporting Items for practice Guidelines in Healthcare checklist and the Appraisal of Guidelines for Research and Evaluation (2nd version) instrument, respectively. Results: Ten CPGs were included, with reporting rates between 51.4 and 88.6%. Seven of these were of moderate to high methodological quality. Seventeen CAM modalities were implicated, involving phytotherapeutics, mind-body practice, art therapy, and homeopathy. Applied relaxation was included in 70% CPGs, which varied in degree of support for its use in the treatment of generalised anxiety disorder. There were few recommendations for other therapies/products. Light therapy was not recommended for use in generalised anxiety disorder, and St John's wort and mindfulness were not recommended for use in social anxiety disorder in individual guidelines. Recommendations for the applicability of other therapies/products for treating a specific anxiety disorder were commonly graded as "unclear, unambiguous, or uncertain". No CAM recommendations were provided for separation anxiety disorder, specific phobia or selective mutism. Conclusion: Available guidelines are limited in providing logically explained graded CAM recommendations for anxiety treatment and care. A lack of high-quality evidence and multidisciplinary consultation during the guideline development are two major reasons. High quality and reliable clinical evidence and the engagement of a range of interdisciplinary stakeholders are needed for future CPG development and updating. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022373694, identifier CRD42022373694.

Organotypic Models for Functional Drug Testing of Human Cancers.

In the era of personalized oncology, there have been accelerated efforts to develop clinically relevant platforms to test drug sensitivities of individual cancers. An ideal assay will serve as a diagnostic companion to inform the oncologist of the various treatments that are sensitive and insensitive, thus improving outcome while minimizing unnecessary toxicities and costs. To date, no such platform exists for clinical use, but promising approaches are on the horizon that take advantage of improved techniques in creating human cancer models that encompass the entire tumor microenvironment, alongside technologies for assessing and analyzing tumor response. This review summarizes a number of current strategies that make use of intact human cancer tissues as organotypic cultures in drug sensitivity testing.

Nickel-Catalyzed Asymmetric Decarboxyarylation with NHP Esters of α-Amino Acid to Chiral Benzylamines.

A nickel-catalyzed asymmetric decarboxyarylation of NHP esters via reductive cross-coupling has been established. Utilizing the NHP of amino acid esters as radical precursors furnishes a new protocol in which structurally diverse chiral benzylamines could be accessible. This method has demonstrated excellent catalytic efficiency, high enantioselective control, mild conditions, and good functional group tolerance, thus enabling the late-stage modification of bioactive molecules and pharmaceuticals.

Pneumorrhachis with spontaneous pneumomediastinum in pediatric patients: An 11-year retrospective study in Southern Taiwan.

BACKGROUND: Although uncommon, available evidence suggests that pneumorrhachis (PR) with spontaneous pneumomediastinum (SPM) in adulthood is usually benign and self-limiting. This study aimed to review our experience and identify the risk factors of PR in pediatric patients with SPM. METHODS: Between September 2007 and September 2017, SPM in patients aged ≤18 years was retrospectively reviewed and clinical features and outcomes between SPM patients with and without PR were analyzed. RESULTS: In total, thirty consecutive occurrences of SPM in 29 patients were finally identified and classified into SPM (n = 24) and SPM plus PR (n = 6) groups. No significant differences in received interventional exams, prophylactic antibiotic administration or restriction of oral intake between the two groups were found. Both groups were treated with hospitalization predominantly; but the SPM plus PR group tended to have longer length of hospital stay (median 5.5 vs. 3 days, p = 0.08). PR was observed more frequently in patients with abnormal serum C-reactive protein (CRP) levels (>5 mg/L), identified predisposing factors, and those with more severe grade of SPM (p = 0.005, 0.001 and < 0.001, respectively). On multivariable regression analysis, the SPM plus PR group exhibited more predisposing factors than did the SPM group (coefficient: 0.514, standard error: 0.136, p < 0.001). All patients were successfully treated without morbidity and mortality. CONCLUSION: Although patients with pneumorrhachis retained a higher CRP level, more identified predisposing factors and prolonged inpatient care, conservative management without an extensive work-up would be an appropriate and favorable strategy in pediatrics with concurrent SPM and PR.

Acupuncture for comorbid depression and insomnia in perimenopause: A feasibility patient-assessor-blinded, randomized, and sham-controlled clinical trial.

Background and objective: Whilst acupuncture is widely used for treating psychosomatic diseases, there is little high-quality evidence supporting its application in comorbid perimenopausal depression (PMD) and insomnia (PMI) which are common complaints during climacteric. This feasibility, patient-assessor-blinded, randomized, sham-controlled clinical trial addresses this gap by investigating the efficacy and safety of acupuncture on depressed mood and poor sleep in women with comorbid PMD and PMI. Methods: Seventy eligible participants were randomly assigned to either real-acupuncture (RA) or sham-acupuncture (SA) groups. Either RA or SA treatment were delivered in 17 sessions over 8 weeks. The primary outcomes for mood and sleep were changes on 17-items Hamilton Depression Rating Scale (HAM-D17) and Pittsburgh Sleep Quality Index (PSQI) scores, from baseline to 16-week follow-up. Secondary outcome measures involved anxiety symptoms, perimenopausal symptoms, quality of life, participants' experience of and satisfaction with the acupuncture treatment. Blood samples were taken to measure reproductive hormone levels. Intention-To-Treat and Per-Protocol analyses were conducted with linear mixed-effects models. The James' and Bang's blinding indices were used to assess the adequacy of blinding. Results: Sixty-five participants completed all treatment sessions, and 54 and 41 participants completed the eight- and 16-week follow-ups, respectively. At post-treatment and 8-week follow-up, the RA group showed a significantly greater reduction in PSQI scores than the SA group did; although the reduction of HAM-D17 scores in RA group was significant, the change was not statistically different from that of SA. There were no significant mean differences between baseline and 16-week follow-up in either HAM-D17 or PSQI in either group. There were no significant between-group differences in serum reproductive hormone levels. All treatments were tolerable and no serious adverse events were reported, and the blinding was successful. Conclusion: Acupuncture is safe and can contribute to clinically relevant improvements in comorbid PMD and PMI, with satisfactory short-and medium-term effects. Whether the anti-depressive benefit of acupuncture is specific or non-specific remains to be determined. No evidence was found for any longer-term benefit of acupuncture compared to sham at 16 weeks. Further research is required to elucidate mechanisms underlying the short to medium term effects of acupuncture.

Elevated intramuscular adipose tissue content with a high Ishak fibrosis stage (>3) had a negative effect on liver regeneration in cirrhotic patients undergoing portal vein embolization.

This study investigated the relationship between body composition parameters and changes in future liver remnant volume (FLRV) in hepatocellular carcinoma (HCC) patients undergoing portal vein embolization (PVE) in preparation for right hepatectomy. This retrospective study enrolled 21 patients between May 2013 and October 2020. Body composition parameters, including skeletal muscle attenuation (SMA), skeletal muscle mass index (SMI), intramuscular adipose tissue content (IMAC), and visceral-to-subcutaneous adipose tissue area ratio (VSR), were measured by computed tomography (CT) prior to PVE. Liver volumetry was measured before and at least 5 weeks after PVE. The mean interval between two CT volumetries was 9.1 ± 4.9 weeks, the mean value of increase in FLRV (ΔFLRV) was 236.0 ± 118.3 cm3 , the ratio of increased FLRV (ΔFLRV%) was 55.7 ± 29.4%, and the rate of increased FLRV was 31.0 ± 18.8 (cm3 /week). Subjects with high IMAC showed significantly lower (p = 0.044) ΔFLRV% than those with normal IMAC. Furthermore, ΔFLRV% was linearly reduced (p for trend = 0.043) among those with low Ishak fibrosis stage (<3) + normal IMAC (76.1 ± 36.8%), those with low Ishak fibrosis stage (<3) + high IMAC or high Ishak fibrosis stage (>3) + normal IMAC (54.0 ± 24.1%), and those with high Ishak fibrosis stage (>3) + low IMAC (28.7 ± 1.6%) (p for trend = 0.043). Our data indicated that high IMAC with a high Ishak fibrosis stage (>3) had a significant negative effect on ΔFLRV%.

Higher pre-treatment skin sympathetic nerve activity and elevated resting heart rate after chemoradiotherapy predict worse esophageal cancer outcomes.

BACKGROUND: Chemoradiotherapy (CRT), which might affect the autonomic system, is the mainstay therapy for advanced esophageal squamous cell carcinoma (ESCC). Autonomic dysfunction has been found to possibly lead to cancer mortality in those with elevated resting heart rates (RHR). Skin sympathetic nerve activity (SKNA) is a new method of stimulating electrical signals in skin to evaluate autonomic function from sympathetic tone. In this study, we investigated the association between changes in RHR and autonomic function and ESCC mortality. METHODS: Thirty-nine stage II-IV ESCC patients receiving CRT between March 2019 and November 2020 were prospectively enrolled and carefully selected, followed up and received the same meticulous supportive care. Serial RHR was recorded every two weeks from before CRT to eight weeks after CRT and average SKNA were recorded before and four weeks after CRT. All-cause mortality was defined as primary outcome. RESULTS: We found the RHR of ESCC patients to be significantly elevated and peaking at four weeks after CRT (p < 0.001) and then to gradually decrease. Those with an elevated RHR above the cutoff level (18 beat-per-minute) at eight weeks after CRT had worse overall survival. In addition, those with higher baseline sympathetic tone (average SKNA ≥ 0.86 µV) also had poor outcome. CONCLUSIONS: Increased pre-treatment sympathetic tone and elevated RHR after CRT are alarm signs of poor ESCC outcome. Further exploration of the mechanisms underlying these associations could potentially lead to intervention strategies for reducing mortality. TRIAL REGISTRATION: This study is registered with ClinicalTrials.gov, identifier: NCT03243448.

A two-stage genome-wide association study to identify novel genetic loci associated with acute radiotherapy toxicity in nasopharyngeal carcinoma.

BACKGROUND: Genetic variants associated with acute side effects of radiotherapy in nasopharyngeal carcinoma (NPC) remain largely unknown. METHODS: We performed a two-stage genome-wide association analysis including a total of 1084 patients, where 319 individuals in the discovery stage were genotyped for 688,783 SNPs using whole genome-wide screening microarray. Significant variants were then validated in an independent cohort of 765 patients using the MassARRAY system. Gene mapping, linkage disequilibrium, genome-wide association analysis, and polygenic risk score were conducted or calculated using FUMA, LDBlockShow, PLINK, and PRSice software programs, respectively. RESULTS: Five SNPs (rs6711678, rs4848597, rs4848598, rs2091255, and rs584547) showed statistical significance after validation. Radiotherapy toxicity was more serious in mutant minor allele carriers of all five SNPs. Stratified analysis further indicated that rs6711678, rs4848597, rs4848598, and rs2091255 correlated with skin toxicity in patients of EBV positive, late stage (III and IV), receiving both concurrent chemoradiotherapy and induction/adjuvant chemotherapy, and with OR values ranging from 1.92 to 2.66. For rs584547, high occurrence of dysphagia was found in A allele carriers in both the discovery (P = 1.27 × 10- 6, OR = 1.55) and validation (P = 0.002, OR = 4.20) cohorts. Furthermore, prediction models integrating both genetic and clinical factors for skin reaction and dysphagia were established. The area under curve (AUC) value of receiver operating characteristic (ROC) curves were 0.657 (skin reaction) and 0.788 (dysphagia). CONCLUSIONS: Rs6711678, rs4848597, rs4848598, and rs2091255 on chromosome 2q14.2 and rs584547 were found to be novel risk loci for skin toxicity and dysphagia in NPC patients receiving radiotherapy. TRIAL REGISTRATION: Chinese Clinical Trial Register (registration number: ChiCTR-OPC-14005257 and CTXY-140007-2).

A zinc finger suppressor involved in stress resistance, cell wall integrity, conidiogenesis, and autophagy in the necrotrophic fungal pathogen Alternaria alternata.

The tangerine pathotype of Alternaria alternata can withstand high-level reactive oxygen species (ROS). By analyzing loss- and gain-of-function mutants, this study demonstrated that a Cys2His2 zinc finger-containing transcription regulator, A. alternata Stress Response Regulator 1 (AaSRR1), plays a negative role in resistance to peroxides and singlet-oxygen-generating compounds. AaSRR1 plays no role in cellular susceptibility or resistance to superoxide-producing compounds. AaSRR1 also negatively regulates conidiogenesis, maintenance of cell wall and membrane integrities, and chitin biosynthesis. Some wild-type hyphae displayed necrosis after exposure to 30 mM H2O2, whereas AaSRR1 deficient mutant (ΔAaSRR1) hyphae had visible granules and vacuoles. sGFP-AaATG8 proteolysis assays revealed that H2O2 and starvation could trigger autophagy formation in both wild type and ΔAaSRR1. Autophagy occurred at higher rates in ΔAaSRR1 than wild type under both conditions, particularly after H2O2 treatments, indicating that autophagy might contribute to ROS resistance. Upon exposure to H2O2 or under starvation, AaSRR1 was translocated into the nucleus, even though the expression of AaSRR1 was decreased. AaSRR1 is required for vegetative growth but is dispensable for fungal virulence as assayed on detached calamondin leaves. AaSRR1 suppressed the expression of the gene encoding a HOG1 mitogen-activated protein (MAP) kinase implicated in ROS resistance. Mutation of AaSRR1 increased catalase activity but decreased superoxide dismutase activity, leading to fewer ROS accumulation in the cytosol. Nevertheless, our results indicated that AaSRR1 is a transcription suppressor for ROS resistance. This study also revealed tradeoffs between stress responses and hyphal growth in A. alternata.

Low-Dose SARS-CoV-2 S-Trimer with an Emulsion Adjuvant Induced Th1-Biased Protective Immunity.

During the sustained COVID-19 pandemic, global mass vaccination to achieve herd immunity can prevent further viral spread and mutation. A protein subunit vaccine that is safe, effective, stable, has few storage restrictions, and involves a liable manufacturing process would be advantageous to distribute around the world. Here, we designed and produced a recombinant spike (S)-Trimer that is maintained in a prefusion state and exhibits a high ACE2 binding affinity. Rodents received different doses of S-Trimer (0.5, 5, or 20 µg) antigen formulated with aluminum hydroxide (Alum) or an emulsion-type adjuvant (SWE), or no adjuvant. After two vaccinations, the antibody response, T-cell responses, and number of follicular helper T-cells (Tfh) or germinal center (GC) B cells were assessed in mice; the protective efficacy was evaluated on a Syrian hamster infection model. The mouse studies demonstrated that adjuvating the S-Trimer with SWE induced a potent humoral immune response and Th1-biased cellular immune responses (in low dose) that were superior to those induced by Alum. In the Syrian hamster studies, when S-Trimer was adjuvanted with SWE, higher levels of neutralizing antibodies were induced against live SARS-CoV-2 from the original lineage and against the emergence of variants (Beta or Delta) with a slightly decreased potency. In addition, the SWE adjuvant demonstrated a dose-sparing effect; thus, a lower dose of S-Trimer as an antigen (0.5 µg) can induce comparable antisera and provide complete protection from viral infection. These data support the utility of SWE as an adjuvant to enhance the immunogenicity of the S-Trimer vaccine, which is feasible for further clinical testing.

Interactive Digital Game for Improving Visual-Perceptual Defects in Children With a Developmental Disability: Randomized Controlled Trial.

BACKGROUND: Visual-perceptual defects in children can negatively affect their ability to perform activities of daily living. Conventional rehabilitation training for correcting visual-perceptual defects has limited training patterns and limited interactivity, which makes motivation difficult to sustain. OBJECTIVE: We aimed to develop and evaluate an interactive digital game system for correcting visual-perceptual defects and evaluate its effectiveness. METHODS: Participants were children aged 5 to 10 years with a diagnosis of visual-perceptual defect associated with a developmental disability. The children were randomized into a digital game group who received the traditional course of rehabilitation combined with an interactive digital game intervention (n=12) and a standard rehabilitation group (n=11) who only received the traditional course of rehabilitation. Each group underwent rehabilitation once a week for 4 weeks. Overall improvement in Test of Visual Perceptual Skills 3rd edition (TVPS-3) score and overall improvement in performance in the interactive digital game were evaluated. Parents and therapists were asked to complete a satisfaction questionnaire. RESULTS: After 4 weeks, the TVPS-3 score had significantly increased (P=.002) in the digital game group (pre: mean 41.67, SD 13.88; post: 61.50, SD 21.64). In the standard rehabilitation group, the TVPS-3 score also increased, but the increase was not statistically significant (P=.58). Additionally, TVPS-3 score increases were significantly larger for the digital game group compared with those for the standard rehabilitation group (P=.005). Moreover, both parents and therapists were highly satisfied with the system. All 5 themes of satisfaction had mean scores higher than 4 in a 5-point scale questionnaire (mean 4.30, SD 0.56). CONCLUSIONS: The system has potential applications for improving visual-perceptual function in children undergoing medical rehabilitation for developmental disability. TRIAL REGISTRATION: ClinicalTrials.gov NCT05016492; http://clinicaltrials.gov/ct2/show/NCT05016492.

Protective role of casuarinin from Melastoma malabathricum against a mouse model of 5-fluorouracil-induced intestinal mucositis: Impact on inflammation and gut microbiota dysbiosis.

BACKGROUND: 5-FU-induced intestinal mucositis (FUIIM) is a common gastrointestinal side effect of chemotherapy, leading to gastric pain in clinical cancer patients. In a previous study, we demonstrated that neutrophil elastase (NE) inhibitors could alleviate FUIIM and manipulate the homeostasis of the gut microbiota. The root of Melastoma malabathricum, also called Ye-Mu-Dan, has been used as a traditional Chinese medicine for gastrointestinal disease. Water extract of the roots of M. malabathricum exhibits an inhibitory effect on NE, with an IC50 value of 9.13 µg/ml. PURPOSE: In this study, we aimed to isolate an anti-NE compound from the root of M. malabathricum and to determine the protective effect of the bioactive component on a mouse model of FUIIM with respect to tissue damage, inflammation, intestinal barrier dysfunction, and gut microbiota dysbiosis. METHODS: A water extract of the roots of M. malabathricum was prepared and its major bioactive compound, was identified using bioactivity-guided fractionation. The effects of samples on the inhibition of NE activity were evaluated using enzymatic assays. To evaluate the effects of the bioactive compound in an FUIIM animal model, male C57BL/6 mice treated with or without casuarinin (50 and 100 mg/kg/day, p.o.), and then received of 5-fluorouracil (50 mg/kg/day) intraperitoneally for 5 days to induce FUIIM. Histopathological staining was used to monitor the tissue damage, proliferation of intestinal crypts, and expression of tight junction proteins. The inflammation score was estimated by determining the levels of oxidative stress, neutrophil-related proteases, and proinflammatory cytokines in tissue and serum. The ecology of the gut microbiota was evaluated using 16S rRNA gene sequencing. RESULTS: Casuarinin had the most potent and selective effect against NE, with an IC50 value of 2.79 ± 0.07 µM. Casuarinin (100 mg/kg/day, p.o.) significantly improved 5-FU-induced body weight loss together with food intake reduction, and it also significantly reversed villus atrophy, restored the proliferative activity of the intestinal crypts, and suppressed inflammation and intestinal barrier dysfunction in the mouse model of FUIIM. Casuarinin also reversed 5-FU-induced gut microbiota dysbiosis, particularly the abundance of Actinobacteria, Candidatus Arthromitus, and Lactobacillus murinus, and the Firmicutes-to-Bacteroidetes ratio. CONCLUSION: This study firstly showed that casuarinin isolated from the root part of M. malabathricum could be used as a NE inhibitor, whereas it could improve FUIIM by modulating inflammation, intestinal barrier dysfunction, and gut microbiota dysbiosis. In summary, exploring anti-NE natural product may provide a way to find candidate for improvement of FUIIM.

Monoclonal antibody targeting the conserved region of the SARS-CoV-2 spike protein to overcome viral variants.

Most therapeutic mAbs target the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2. Unfortunately, the RBD is a hot spot for mutations in SARS-CoV-2 variants, which will lead to loss of the neutralizing function of current therapeutic mAbs. Universal mAbs for different variants are necessary. We identified mAbs that recognized the S2 region of the spike protein, which is identical in different variants. The mAbs could neutralize SARS-CoV-2 infection and protect animals from SARS-CoV-2 challenge. After cloning the variable region of the light chain and heavy chain, the variable region sequences were humanized to select a high-affinity humanized mAb, hMab5.17. hMab5.17 protected animals from SARS-CoV-2 challenge and neutralized SARS-CoV-2 variant infection. We further identified the linear epitope of the mAb, which is not mutated in any variant of concern. These data suggest that a mAb recognizing the S2 region of the spike protein will be a potential universal therapeutic mAb for COVID-19.

The experience of use of percutaneous transhepatic biliary drainages for early biliary complications after liver transplantation.

This study aimed to describe our experience and discuss the results, controversies, and the use of percutaneous transhepatic biliary drainage (PTBD) in patients with biliary complications after liver transplantation (LT). Between November 2009 and August 2020, 76 consecutive patients who underwent 77 LTs (44 deceased donor LTs and 33 living donor LTs [LDLT]) were enrolled retrospectively. Endoscopic therapy as initial approach and PTBD as rescue therapy were used for patients with biliary complications. There were 31 patients (31/76, 40.8%) with biliary complications, and two of them died (2/31, 6.5%). Clinical success rate of endoscopic therapy alone was 71.0% (22/31). The remaining nine patients received salvage PTBD and their clinical results were observed according to whether their intrahepatic bile ducts (IHBDs) was dilated (group A, n = 5) or not (group B, n = 4). In group A, the technical and long-term clinical success rates of PTBD were 100% and 20%, respectively. These five patients received PTBD ranging from 75 to 732 days after their LTs, and no procedure-related complications were encountered. In group B, the technical and long-term clinical success rates of PTBD were 50% and 25%, respectively. Three group B patients (75%) underwent PTBD within 30 days after LDLT and had lethal complications. One patient had graft laceration and survived after receiving timely re-transplantation. The other two patients died of sepsis due to PTBD-related bilioportal fistula or multiple liver abscesses. Our experience showed salvage PTBD played a limited role in biliary complications without dilated IHBDs within 1 month after LT.

Self-efficacy as a crucial psychological predictor of treatment adherence among elderly people living with HIV: analyses based on the health belief model.

Medication adherence to antiretroviral therapy (ART) among elderly people living with HIV (PLWH) is of serious concern. Our study aimed to understand the medication adherence of elderly PLWH under ART based on the health belief model (HBM). A baseline survey with a total of 529 elderly PLWH was conducted in Sichuan. Logistic and linear regression analysis, mediation analysis, and path analysis based on prior evidence were used. Only self-efficacy showed direct associations with medication adherence in the last four days (ORm = 1.37, 95%CI: 1.11, 1.70) and the last month (ORm = 1.39, 95%CI: 1.18, 1.63) in the multivariate analysis. Self-efficacy mediated the relations between perceived benefits, perceived barriers, cues to action and medication adherence. Inner relations existed within the HBM. In addition to the direct effects, perceived benefits (ß = 0.149, p = 0.031; ß = 0.093, p = 0.005), perceived barriers (ß = -0.070, p = 0.008; ß = -0.062, p = 0.012), and cues to action (ß = 0.184, p = 0.013; ß = 0.135, p = 0.014) showed indirect effects on medication adherence in the last four days and the last month, respectively. HBM may be effective in predicting medication adherence of elderly PLWH, and self-efficacy may be a crucial predictor and mediator. Efforts should be focused on how to enhance elderly PLWH's self-efficacy without neglect of other medication beliefs.

Coniochaeta elegans sp. nov., Coniochaeta montana sp. nov. and Coniochaeta nivea sp. nov., three new species of endophytes with distinctive morphology and functional traits.

A growing interest in fungi that occur within symptom-less plants and lichens (endophytes) has uncovered previously uncharacterized species in diverse biomes worldwide. In many temperate and boreal forests, endophytic Coniochaeta (Sacc.) Cooke (Coniochaetaceae, Coniochaetales, Sordariomycetes, Ascomycota) are commonly isolated on standard media, but rarely are characterized. We examined 26 isolates of Coniochaeta housed at the Gilbertson Mycological Herbarium. The isolates were collected from healthy photosynthetic tissues of conifers, angiosperms, mosses and lichens in Canada, Sweden and the United States. Their barcode sequences (nuclear ribosomal internal transcribed spacer and 5.8S; ITS rDNA) were ≤97% similar to any documented species available through GenBank. Phylogenetic analyses based on two loci (ITS rDNA and translation elongation factor 1-alpha) indicated that two isolates represented Coniochaeta cymbiformispora, broadening the ecological niche and geographic range of a species known previously from burned soil in Japan. The remaining 24 endophytes represented three previously undescribed species that we characterize here: Coniochaeta elegans sp. nov., Coniochaeta montana sp. nov. and Coniochaeta nivea sp. nov. Each has a wide host range, including lichens, bryophytes and vascular plants. C. elegans sp. nov. and C. nivea sp. nov. have wide geographic ranges. C. montana sp. nov. occurs in the Madrean biome of Arizona (USA), where it is sympatric with the other species described here. All three species display protease, chitinase and cellulase activity in vitro. Overall, this study provides insight into the ecological and evolutionary diversity of Coniochaeta and suggests that these strains may be amenable for studies of traits relevant to a horizontally transmitted, symbiotic lifestyle.

Effect of Non-lockdown Social Distancing and Testing-Contact Tracing During a COVID-19 Outbreak in Daegu, South Korea, February to April 2020: A Modeling Study.

OBJECTIVE: In Spring 2020, South Korea applied non-lockdown social distancing (avoiding mass gathering and non-essential social engagement, without restricting the movement of people who were not patients or contacts), testing-and-isolation (testing), and tracing-and-quarantine the contacts (contact tracing) to successfully control the first large-scale COVID-19 outbreak outside China. However, the relative contributions of these two interventions remain uncertain. METHODS: We constructed an SEIR model of SARS-CoV-2 transmission (disproportionately through superspreading events) and fit the model to outbreak data in Daegu, South Korea, from February to April 2020. We assessed the effect of non-lockdown social distancing (population-wide control measures) and/or testing-contact tracing (individual-specific control measures), alone or combined, in terms of the basic reproductive number (R0) and the trajectory of the epidemic. RESULTS: The point estimate for baseline R0 is 3.6 (sensitivity analyses range: 2.3 to 5.6). Combined interventions of non-lockdown social distancing and testing-contact tracing can suppress R0 to less than one and rapidly contain the epidemic, even under the worst scenario with a high baseline R0 of 5.6. In contrast, either intervention alone will fail to suppress R0. Non-lockdown social distancing alone just postpones the peak of the epidemic, while testing-contact tracing alone only flattens the curve but does not contain the outbreak. CONCLUSIONS: To successfully control a large-scale COVID-19 outbreak, both non-lockdown social distancing and testing-contact tracing must be implemented. The two interventions are synergistic.