Background/Aims: Laryngeal symptoms are largely treated with empiric proton pump inhibitor (PPI) therapy if no apparent pathology shown on ear, nose, and throat evaluation and reflux-related etiologies are suspected. However, treatment response remains unsatisfactory. This study aimed to investigate the clinical and physiological characteristics of patients with PPI-refractory laryngeal symptoms. Methods: Patients with persistent laryngeal symptoms despite PPI treatment for ≥ 8 weeks were recruited. A multidisciplinary evaluationcomprising validated questionnaires for laryngeal symptoms (reflux symptom index [RSI]), gastroesophageal reflux disease symptoms, psychological comorbidity (5-item brief symptom rating scale [BSRS-5]) and sleep disturbance (Pittsburgh sleep quality index [PSQI]), esophagogastroduodenoscopy, ambulatory impedance-pH monitoring, and high-resolution impedance manometry were performed.Healthy asymptomatic individuals were also recruited for comparison of psychological morbidity and sleep disturbances. Results: Ninety-seven adult patients and 48 healthy volunteers were analyzed. The patients had markedly higher prevalence of psychological distress (52.6% vs 2.1%, P < 0.001) and sleep disturbance (82.5% vs 37.5%, P < 0.001) than the healthy volunteers. There were significant correlations between RSI and BSRS-5 scores, and between RSI and PSQI scores (r = 0.26, P = 0.010, and r = 0.29, P = 0.004, respectively). Fifty-eight patients had concurrent gastroesophageal reflux disease symptoms. They had more prominent sleep disturbances (89.7% vs 71.8%, P < 0.001) than those with laryngeal symptoms alone but similar reflux profiles and esophageal motility. Conclusions PPI-refractory laryngeal symptoms are mostly associated with psychological comorbidities and sleep disturbances. Recognition of these psychosocial comorbidities may help optimize management in these patients.

Background/Aims: Non-alcoholic fatty liver disease (NAFLD) is associated with the development of cardiovascular disease. While existing studies have examined cardiac remodeling in NAFLD, there has been less emphasis on the development of carotid atherosclerosis and stroke. We sought to conduct a meta-analysis to quantify the prevalence, risk factors, and degree of risk increment of carotid atherosclerosis and stroke in NAFLD. Methods: Embase and Medline were searched for articles relating to NAFLD, carotid atherosclerosis, and stroke. Proportional data was analysed using a generalized linear mixed model. Pairwise meta-analysis was conducted to obtain odds ratio or weighted mean difference for comparison between patients with and without NAFLD. Results: From pooled analysis of 30 studies involving 7,951 patients with NAFLD, 35.02% (95% confidence interval [CI], 27.36–43.53%) had carotid atherosclerosis with an odds ratio of 3.20 (95% CI, 2.37–4.32; P<0.0001). Pooled analysis of 25,839 patients with NAFLD found the prevalence of stroke to be 5.04% (95% CI, 2.74–9.09%) with an odds ratio of 1.88 (95% CI, 1.23–2.88; P=0.02) compared to non-NAFLD. The degree of steatosis assessed by ultrasonography in NAFLD was closely associated with risk of carotid atherosclerosis and stroke. Older age significantly increased the risk of developing carotid atherosclerosis, but not stroke in NAFLD. Conclusions This meta-analysis shows that a stepwise increment of steatosis of NAFLD can significantly increase the risk of carotid atherosclerosis and stroke development in NAFLD. Patients more than a third sufferred from carotid atherosclerosis and routine assessment of carotid atherosclerosis is quintessential in NAFLD.

INTRODUCTION: Disease outbreaks such as the COVID-19 pandemic significantly heighten the psychological stress of healthcare workers (HCWs). The objective of this study was to understand the factors contributing to the perceived stress levels of HCWs in a public primary care setting during the COVID-19 pandemic, including their training, protection and support (TPS), job stress (JS), and perceived stigma and interpersonal avoidance. METHODS: This cross-sectional study using an electronic self-administered questionnaire was conducted at the National Healthcare Group Polyclinics in March 2020. Data was collected anonymously. Analysis was performed using regression modelling. RESULTS: The response rate was 69.7% (n = 1,040). The mean perceived stress level of HCWs in various departments ranged from 17.2 to 20.3. Respondents who reported higher perceived stress were those who made alternative living arrangements, were more affected by the current pandemic, reported higher JS and were Muslims. Respondents who reported lower perceived stress were those who had been through the severe acute respiratory syndrome epidemic in 2003 and H1N1 pandemic in 2009 as HCWs, and those who had higher confidence in the organisation's TPS. CONCLUSION All HCWs, regardless of their scope of work, were similarly stressed by the current pandemic compared to the general population. Improving the confidence of HCWs in their training, protection and the support of personal protective equipment, and retaining experienced HCWs who can provide advice and emotional support to younger colleagues are important. Adequate psychological support for HCWs in the pandemic can be transformed into reserves of psychological resilience for future disease outbreaks.
COVID-19/epidemiology* ; Cross-Sectional Studies ; Health Personnel/psychology* ; Humans ; Influenza A Virus, H1N1 Subtype ; Pandemics ; Primary Health Care ; SARS-CoV-2 ; Stress, Psychological

Inflammation alters the neural stem cell (NSC) lineage from neuronal to astrogliogenesis. However, the underlying mechanism is elusive. Autophagy contributes to the decline in adult hippocampal neurogenesis under E. coli lipopolysaccharide (LPS) stimulation. SRY-box transcription Factor 2 (SOX2) is critical for NSC self-renewal and proliferation. In this study, we investigated the role of SOX2 in induced autophagy and hippocampal adult neurogenesis under LPS stimulation. LPS (5 ng•100 g -1 •hour -1 for 7 days) was intraperitoneally infused into male Sprague–Dawley rats (8 weeks old) to induce mild systemic inflammation. Beclin 1 and autophagy protein 12 (Atg12) were significantly upregulated concurrent with decreased numbers of Ki67- and doublecortin (DCX)-positive cells in the dentate gyrus. Synchronically, the levels of phospho(p)-mTOR, the p-mTOR/mTOR ratio, p-P85s6k, and the p-P85s6k/P85s6k ratio were suppressed. In contrast, SOX2 expression was increased. The fluorescence micrographs indicated that the colocalization of Beclin 1 and SOX2 was increased in the subgranular zone (SGZ) of the dentate gyrus. Moreover, increased S100β-positive astrocytes were colocalized with SOX2 in the SGZ. Intracerebroventricular infusion of 3-methyladenine (an autophagy inhibitor) effectively prevented the increases in Beclin 1, Atg12, and SOX2. The SOX2 + -Beclin 1 + and SOX2 + -S100β + cells were reduced. The levels of p-mTOR and p-P85s6k were enhanced. Most importantly, the number of DCX-positive cells was preserved. Altogether, these data suggest that LPS induced autophagy to inactivate the mTOR/P85s6k pathway, resulting in a decline in neural differentiation. SOX2 was upregulated to facilitate the NSC lineage, while the autophagy milieu could switch the SOX2-induced NSC lineage from neurogenesis to astrogliogenesis.

Introduction: This study aimed to determine the prevalence and factors associated with female sexual dysfunction in an outpatient clinic in Malaysia. Methods: The study was conducted among female patients aged 50 years and older who attended the outpatient clinic of a public hospital in Malaysia. A self-administered questionnaire was used that was based on the Malay version of the Female Sexual Function Index questionnaire. The predictors of female sexual dysfunction were identified using multivariate logistic regression analysis. Results: A total of 263 females were recruited in this study, with a mean age of 60.6 ± 6.7 years. The distribution of the respondents’ ethnicities was mostly Malay (42.2%), followed by Chinese (41.8%) and Indian (16.0%). The prevalence of female sexual dysfunction among participants was 68.8%. The prevalence of the subscales of female sexual dysfunction was as follows: desire (85.2%), satisfaction (74.9%), arousal (71.1%), lubrication (66.9%), pain (61.2%), and orgasm (60.8%). According to multivariate logistic regression, patients of Indian ethnicity had an increased risk of female sexual dysfunction (OR=16.60, 95% CI=2.54–108.63), and a higher frequency of sexual intercourse was correlated with a lower risk of female sexual dysfunction (OR=0.13, 95% CI=0.08–0.24). Conclusion Seven-tenths of the middle-aged female patients attending the outpatient clinic suffered from female sexual dysfunction. Indian ethnicity and having a lower frequency of sexual intercourse were predictors of female sexual dysfunction. Future intervention studies are needed to address this problem.
Prevalence ; Sexual Dysfunction, Physiological ; Women ; Ambulatory Care Facilities ; Middle Aged

The arachidonic acid (AA) metabolic pathway participates in various physiological processes as well as in the development of malignancies. We analyzed genomic alterations in AA metabolic enzymes in the Cancer Genome Atlas (TCGA) prostate cancer (PCa) dataset and found that the gene encoding soluble epoxide hydrolase (EPHX2) is frequently deleted in PCa. EPHX2 mRNA and protein expression in PCa was examined in multiple datasets by differential gene expression analysis and in a tissue microarray by immunohistochemistry. The expression data were analyzed in conjunction with clinicopathological variables. Both the mRNA and protein expression levels of EPHX2 were significantly decreased in tumors compared with normal prostate tissues and were inversely correlated with the Gleason grade and disease-free survival time. Furthermore, EPHX2 mRNA expression was significantly decreased in metastatic and recurrent PCa compared with localized and primary PCa, respectively. In addition, EPHX2 protein expression correlated negatively with Ki67 expression. In conclusion, EPHX2 deregulation is significantly correlated with the clinical characteristics of PCa progression and may serve as a prognostic marker for PCa.

INTRODUCTION: The impact of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) on the risk of malignancy (ROM) in fine-needle aspiration cytology (FNAC) per The Bethesda System for Reporting Thyroid Cytopathology has not been well reported in Singapore. METHODS: We retrospectively identified 821 thyroid nodules with preoperative FNAC from 788 patients out of 1,279 consecutive thyroidectomies performed between January 2010 and August 2016 in a tertiary general hospital in Singapore. Possible cases of NIFTP were reviewed for reclassification and the impact of NIFTP on ROM was analysed. RESULTS: The incidence of NIFTP was 1.2% (10 out of 821). If NIFTP is considered benign, ROM in Bethesda I through VI were 8.6%, 3.5%, 26.3%, 20.0%, 87.7%, 97.0% versus 8.6%, 4.2%, 28.1%, 26.7%, 89.2% and 100% if NIFTP is considered malignant. Eight patients with NIFTP had follow-up of 15 to 110 months. One had possible rib metastasis as evidenced by I131 uptake but remained free of structural or biochemical disease during a follow-up period of 110 months. None had lymph node metastasis at presentation, nor locoregional or distant recurrence. CONCLUSION Classifying NIFTP as benign decreased ROM in Bethesda II through VI, but the benignity of NIFTP requires more prospective studies to ascertain. The impact of NIFTP on ROM in our institution also appears to be lower than that reported in the Western studies.
Adenocarcinoma, Follicular/epidemiology* ; Humans ; Prospective Studies ; Retrospective Studies ; Singapore/epidemiology* ; Thyroid Neoplasms/epidemiology*

Background: Despite the lack of official COVID-19 statistics, various workplaces and occupations have been at the center of COVID-19 outbreaks. We aimed to compare legal measures and governance established for managing COVID-19 infection risks at workplaces in nine Asia and Pacific countries and to recommend key administrative measures. Methods: We collected information on legal measures and governance from both general citizens and workers regarding infection risks such as COVID-19 from industrial hygiene professionals in nine countries (Indonesia, India, Japan, Malaysia, New Zealand, Republic of the Philippines, Republic of Korea, Taiwan, and Thailand) using a structured questionnaire. Results: A governmental body overseeing public health and welfare was in charge of containing the spread and occurrence of infectious diseases under an infectious disease control and prevention act or another special act, although the name of the pertinent organizations and legislation vary among countries. Unlike in the case of other traditional hazards, there have been no specific articles or clauses describing the means of mitigating virus risk in the workplace that are legally required of employers, making it difficult to define the responsibilities of the employer. Each country maintains own legal systems regarding access to the duration, administration, and financing of paid sick leave. Many workers may not have access to paid sick leave even if it is legally guaranteed. Conclusion Specific legal measures to manage infectious disease risks, such as providing proper personal protective equipment, education, engineering control measures, and paid sick leave are recommended to be stipulated in Industrial safety and health-related acts.