Background/Aims: Distal mean nocturnal baseline impedance (MNBI) measuring via pH-impedance may be valuable in diagnosing patients with suspected laryngopharyngeal reflux (LPR). However, its wide adoption is hindered by cost and invasiveness. This study investigates whether baseline impedance measured during high-resolution impedance manometry (HRIM-BI) can predict pathological MNBI. Methods: A cross-sectional study in Taiwan included 74 subjects suspected of LPR, who underwent HRIM (MMS) and pH-impedance testing (Diversatek), after stopping proton pump inhibitors for more than 7 days. Subjects with grade C or D esophagitis or Barrett’s esophagus were excluded. The cohort was divided into 2 groups: those with concomitant typical reflux symptoms (CTRS, n = 28) and those with isolated LPR symptoms (ILPRS, n = 46). HRIM-BI measurements focused on both distal and proximal esophagi. Pathological MNBI was identified as values below 2065 Ω, measured 3 cm above the lower esophageal sphincter. Results: In all subjects, distal HRIM-BI values correlated weakly with distal MNBI(r = 0.34-0.39, P < 0.005). However, in patients with ILPRS, distal HRIM-BI corelated moderately with distal MNBI(r = 0.43-0.48, P < 0.005). The areas under the receiver operating characteristic curve was 0.78 (P = 0.001) with a sensitivity of 0.83 and a specificity of 0.68. No correlation exists between distal HRIM-BI and distal MNBI in patients with CTRS, and between proximal HRIM-BI and proximal MNBI in both groups. Conclusions Distal HRIM-BI from HRIM may potentially predict pathological MNBI in patients with ILPRS, but not in those with CTRS. Future outcome studies linked to the metric are warranted.

Background/Aims: Distal mean nocturnal baseline impedance (MNBI) measuring via pH-impedance may be valuable in diagnosing patients with suspected laryngopharyngeal reflux (LPR). However, its wide adoption is hindered by cost and invasiveness. This study investigates whether baseline impedance measured during high-resolution impedance manometry (HRIM-BI) can predict pathological MNBI. Methods: A cross-sectional study in Taiwan included 74 subjects suspected of LPR, who underwent HRIM (MMS) and pH-impedance testing (Diversatek), after stopping proton pump inhibitors for more than 7 days. Subjects with grade C or D esophagitis or Barrett’s esophagus were excluded. The cohort was divided into 2 groups: those with concomitant typical reflux symptoms (CTRS, n = 28) and those with isolated LPR symptoms (ILPRS, n = 46). HRIM-BI measurements focused on both distal and proximal esophagi. Pathological MNBI was identified as values below 2065 Ω, measured 3 cm above the lower esophageal sphincter. Results: In all subjects, distal HRIM-BI values correlated weakly with distal MNBI(r = 0.34-0.39, P < 0.005). However, in patients with ILPRS, distal HRIM-BI corelated moderately with distal MNBI(r = 0.43-0.48, P < 0.005). The areas under the receiver operating characteristic curve was 0.78 (P = 0.001) with a sensitivity of 0.83 and a specificity of 0.68. No correlation exists between distal HRIM-BI and distal MNBI in patients with CTRS, and between proximal HRIM-BI and proximal MNBI in both groups. Conclusions Distal HRIM-BI from HRIM may potentially predict pathological MNBI in patients with ILPRS, but not in those with CTRS. Future outcome studies linked to the metric are warranted.

Background/Aims: Distal mean nocturnal baseline impedance (MNBI) measuring via pH-impedance may be valuable in diagnosing patients with suspected laryngopharyngeal reflux (LPR). However, its wide adoption is hindered by cost and invasiveness. This study investigates whether baseline impedance measured during high-resolution impedance manometry (HRIM-BI) can predict pathological MNBI. Methods: A cross-sectional study in Taiwan included 74 subjects suspected of LPR, who underwent HRIM (MMS) and pH-impedance testing (Diversatek), after stopping proton pump inhibitors for more than 7 days. Subjects with grade C or D esophagitis or Barrett’s esophagus were excluded. The cohort was divided into 2 groups: those with concomitant typical reflux symptoms (CTRS, n = 28) and those with isolated LPR symptoms (ILPRS, n = 46). HRIM-BI measurements focused on both distal and proximal esophagi. Pathological MNBI was identified as values below 2065 Ω, measured 3 cm above the lower esophageal sphincter. Results: In all subjects, distal HRIM-BI values correlated weakly with distal MNBI(r = 0.34-0.39, P < 0.005). However, in patients with ILPRS, distal HRIM-BI corelated moderately with distal MNBI(r = 0.43-0.48, P < 0.005). The areas under the receiver operating characteristic curve was 0.78 (P = 0.001) with a sensitivity of 0.83 and a specificity of 0.68. No correlation exists between distal HRIM-BI and distal MNBI in patients with CTRS, and between proximal HRIM-BI and proximal MNBI in both groups. Conclusions Distal HRIM-BI from HRIM may potentially predict pathological MNBI in patients with ILPRS, but not in those with CTRS. Future outcome studies linked to the metric are warranted.

Patients with a history of cardiovascular disease (CVD) who contract coronavirus disease 2019 (COVID-19) tend to have a worse prognosis and more severe cardiovascular side effects.COVID-19 vaccines, which are intended to prevent COVID-19, may also potentially reduce the severity and complications (including cardiovascular sequelae) of COVID-19, especially in patients with a history of CVD. However, there have also been reports of cardiovascular side effects from COVID-19 vaccines of various brands and types. The purpose of this study is to review the benefits and harms of COVID-19 vaccines in relation to CVD. In this thorough review of the most current evidence on the benefits and harms of COVID-19 vaccines, we present information about the characteristics of cardiovascular complications. Most of the evidence focuses on myocarditis or pericarditis, which are most strongly associated with mRNA vaccines and predominantly occur in young males within days of receiving the second dose. Meanwhile, post-vaccination myocardial infarction is more common in older males, and the first dose of adenoviral vector vaccines appears to play a greater role in this complication. This information may guide us in formulating alternative options and implementing targeted surveillance. Gaining more knowledge about the potential benefits and harms of COVID-19 vaccines will improve our ability to make informed decisions and judgments about the balance of these factors.

A 51-year-old woman presented with metachronous tumor development in bilateral breasts, thyroid, and endometrium. Additional signs and symptoms fulfilled the National Comprehensive Cancer Network criteria for Cowden syndrome. Immunohistochemistry showed loss of PTEN expression in all tumors. Single nucleotide variants, 647 germline variants (including one each in PTEN and MSH3), and 21 somatic mutations within exons were detected in all tumors after whole-exome sequencing. There were 0, 11, and 46 specific somatic mutations in bilateral breasts, thyroid, and endometrial cancers, respectively.Although PTEN mutation is key to the development of Cowden syndrome, DNA repair dysfunction might be the initial driver of mutations. Fewer mutations were required to induce initial bilateral breast carcinomas, with subsequent thyroid and endometrial carcinomas requiring more mutations for induction. When genetic screening is unavailable, breast cancer patients with clinical manifestations of Cowden syndrome must be carefully assessed for secondary malignancies, such as thyroid and endometrial carcinomas.

Circadian disruption is being increasingly recognized as a critical factor in the development and progression of Parkinson’s disease (PD). This review aims to provide an in-depth overview of the relationship between circadian disruption and PD by exploring the molecular, cellular, and behavioral aspects of this interaction. This review will include a comprehensive understanding of how the clock gene system and transcription–translation feedback loops function and how they are diminished in PD. The article also discusses the role of clock genes in the regulation of circadian rhythms, as well as the impact of clock gene dysregulation on mitochondrial function, oxidative stress, and neuroinflammation, including the microbiota-gut-brain axis, which have all been proposed as being crucial mechanisms in the pathophysiology of PD. Finally, this review highlights potential therapeutic strategies targeting the clock gene system and circadian rhythm for the treatment of PD.

INTRODUCTIONProblem-based learning (PBL), a pedagogic concept using a student-centred approach and problem-solving through small group discussions, has been adopted in varying degrees for years at all 11 medical institutes in Taiwan. Much evidence has shown that a number of factors can seriously affect student performance in PBL courses, such as the design of PBL scenarios, the tutors' character and students' attitudes and efforts.

MATERIALS AND METHODSThe aim of this study was to examine how the personal characters or knowledge base of Taiwanese medical students influence their performance in a hybrid-PBL curriculum. A total of 309 (234 male, 75 female) high-school entry undergraduate medical students participated in this survey. Self-assessed personal traits were presented in a 44-item questionnaire with a Big Five factor structure. Knowledge base was assessed by students' score point average (SPA) based on their previous 4-year education in medical school. Peer-assessed performance of students in the PBL curriculum was carried out using a well-developed, reliable and validated evaluation form.

RESULTSEach student's peer-evaluated PBL performance can be divided into 5 principal components, which included control-lead, assist-coordinate, written organisation and compromise- comply (Eigen value >1). The consistency and reliability of the Big Five questionnaire on personal traits was analysed and discordant items were deleted (Cronbach's alpha = 0.72 to 0.86 after deletion). The relationship between the personal traits, knowledge base and PBL performance, as analysed by simple regression, showed that "extraversion" and "openness to experience" were positively related to the "assist-coordinate" characteristic in PBL performance, and "conscientiousness" was positively related to the "control-lead" characteristic in PBL performance. The SPA was positively related to the "assist-coordinate" or "control-lead" characteristic in PBL performance. The "agreeableness" was negatively correlated with the "control-lead" characteristic in PBL performance. After stepwise regression between the Big Five and each component of PBL performance, only the correlation between conscientiousness and control/lead, and between extraversion and assist/coordinate remained significant.

CONCLUSIONKnowledge and personality characteristics appear to be associated with student performance in a hybrid-PBL curriculum. The implications of this study on the future development and application of this assessment tool in medical schools are presented.

Educational Measurement ; Female ; Humans ; Male ; Mental Competency ; psychology ; Problem-Based Learning ; methods ; Retrospective Studies ; Students, Medical ; psychology ; Surveys and Questionnaires ; Taiwan

OBJECTIVETo investigate the inhibitory activities of norcantharidin (NCTD), a demethylated analogue of cantharidin, on Hep3B cells (a human hepatoma cell line) with deficiency of p53.

METHODSThe survival rate of the Hep3B cells after treating with NCTD was measured by MTT assay. Cell cycle of treated cells was analyzed by flow cytometry, and DNA fragmentation was observed by electrophoresis. The influence of inhibitors for various caspases and anti-death receptors antibodies on the NCTD-induced apoptosis in the cells was determined.

RESULTSNCTD treatment resulted in growth inhibition of Hep3B cells in a dose- and time-dependent manner. Cell cycle analysis of the cells after treatment with NCTD for 48 h shows that NCTD induced G(2)M phase arrest occurs at low concentration ([Symbol: see text] 25 μmol/L) but G(0)G(1) phase arrest at high concentration (50 μmol/L). The addition of both caspase-3 and caspase-10 inhibitors completely inhibited DNA fragmentation. Addition of anti-TRAIL/DR5 antibody significantly inhibited DNA fragmentation.

CONCLUSIONNCTD may inhibit the proliferation of Hep3B cells by arresting cell cycle at G(2)M or G(0)G(1) phase, and induce cells apoptosis via TRAIL/DR5 signal transduction through activation of caspase-3 and caspase-10 by a p53-independent pathway.

Antibodies, Neoplasm ; pharmacology ; Antibodies, Neutralizing ; pharmacology ; Apoptosis ; drug effects ; Bridged Bicyclo Compounds, Heterocyclic ; pharmacology ; Carcinoma, Hepatocellular ; enzymology ; pathology ; Caspase 10 ; metabolism ; Caspase 3 ; metabolism ; Caspase Inhibitors ; pharmacology ; Cell Cycle Checkpoints ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; DNA Fragmentation ; drug effects ; Humans ; Immunohistochemistry ; Liver Neoplasms ; enzymology ; pathology ; Receptors, TNF-Related Apoptosis-Inducing Ligand ; metabolism ; Signal Transduction ; drug effects ; TNF-Related Apoptosis-Inducing Ligand ; metabolism ; Tumor Suppressor Protein p53 ; metabolism