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Liver cirrhosis and hepatocellular carcinoma (HCC) are highly prevalent in Australia's Northern Territory. Contributing factors include high levels of alcohol consumption, viral hepatitis and metabolic syndrome. Rural Aboriginal residents form a significant proportion of the Central Australian population and present a challenge to traditional models of liver care. HCC surveillance and variceal screening are core components of liver cirrhosis management.To assess participation in HCC and variceal surveillance programmes in a Central Australian liver cirrhosis patient cohort.Retrospective cohort study of patients with liver cirrhosis presenting to Alice Springs Hospital, Australia between January 1, 2012 and December 31, 2017. Demographic data, disease severity, attendance at hepatology clinics, participation in variceal and/or HCC surveillance programmes was recorded. Regression analyses were conducted to assess factors associated with two independent outcomes: Participation in HCC and variceal surveillance.Of 193 patients were identified. 82 patients (42.4%) were female. 154 patients (80%) identified as Aboriginal. Median Model for End-stage Liver Disease Score at diagnosis was 11. Alcohol was the most common cause of cirrhosis. Aboriginal patients were younger than non-Aboriginal patients (48.4 yearsHCC or variceal surveillance programmes had less uptake amongst Aboriginal patients. Greater emphasis needs to be placed on eliminating cultural obstacles to accessing hepatology services.

Data sharing: The PHOSP-COVID study protocol, consent form, definition, and derivation of clinical characteristics and outcomes, training materials, regulatory documents, information about requests for data access, and other relevant study materials are available online. UK Biobank information can be released once necessary approvals have been obtained. Other data (eg, the R code and protocol) will be made available on reasonable request to the corresponding author. Copyright © 2023 The Author(s). Background: Sleep disturbance is common following hospital admission both for COVID-19 and other causes. The clinical associations of this for recovery after hospital admission are poorly understood despite sleep disturbance contributing to morbidity in other scenarios. We aimed to investigate the prevalence and nature of sleep disturbance after discharge following hospital admission for COVID-19 and to assess whether this was associated with dyspnoea. Methods: CircCOVID was a prospective multicentre cohort substudy designed to investigate the effects of circadian disruption and sleep disturbance on recovery after COVID-19 in a cohort of participants aged 18 years or older, admitted to hospital for COVID-19 in the UK, and discharged between March, 2020, and October, 2021. Participants were recruited from the Post-hospitalisation COVID-19 study (PHOSP-COVID). Follow-up data were collected at two timepoints: an early time point 2–7 months after hospital discharge and a later time point 10–14 months after hospital discharge. Sleep quality was assessed subjectively using the Pittsburgh Sleep Quality Index questionnaire and a numerical rating scale. Sleep quality was also assessed with an accelerometer worn on the wrist (actigraphy) for 14 days. Participants were also clinically phenotyped, including assessment of symptoms (ie, anxiety [Generalised Anxiety Disorder 7-item scale questionnaire], muscle function [SARC-F questionnaire], dyspnoea [Dyspnoea-12 questionnaire] and measurement of lung function), at the early timepoint after discharge. Actigraphy results were also compared to a matched UK Biobank cohort (non-hospitalised individuals and recently hospitalised individuals). Multivariable linear regression was used to define associations of sleep disturbance with the primary outcome of breathlessness and the other clinical symptoms. PHOSP-COVID is registered on the ISRCTN Registry (ISRCTN10980107). Findings: 2320 of 2468 participants in the PHOSP-COVID study attended an early timepoint research visit a median of 5 months (IQR 4–6) following discharge from 83 hospitals in the UK. Data for sleep quality were assessed by subjective measures (the Pittsburgh Sleep Quality Index questionnaire and the numerical rating scale) for 638 participants at the early time point. Sleep quality was also assessed using device-based measures (actigraphy) a median of 7 months (IQR 5–8 months) after discharge from hospital for 729 participants. After discharge from hospital, the majority (396 [62%] of 638) of participants who had been admitted to hospital for COVID-19 reported poor sleep quality in response to the Pittsburgh Sleep Quality Index questionnaire. A comparable proportion (338 [53%] of 638) of participants felt their sleep quality had deteriorated following discharge after COVID-19 admission, as assessed by the numerical rating scale. Device-based measurements were compared to an age-matched, sex-matched, BMI-matched, and time from discharge-matched UK Biobank cohort who had recently been admitted to hospital. Compared to the recently hospitalised matched UK Biobank cohort, participants in our study slept on average 65 min (95% CI 59 to 71) longer, had a lower sleep regularity index (–19%; 95% CI –20 to –16), and a lower sleep efficiency (3·83 percentage points; 95% CI 3·40 to 4·26). Similar results were obtained when comparisons were made with the non-hospitalised UK Biobank cohort. Overall sleep quality (unadjusted effect estimate 3·94; 95% CI 2·78 to 5·10), deterioration in sleep quality following hospital admission (3·00; 1·82 to 4·28), and sleep regularity (4·38; 2·10 to 6·65) were associated with higher dyspnoea scores. Poor sleep quality, deterioration in sleep quality, and sleep regularity were also associated with impaired lung function, as assessed by forced vital capacity. Depending on the sleep metric, anxiety mediated 18–39% of the effect of sleep disturbance on dyspnoea, while muscle weakness mediated 27–41% of this effect. Interpretation: Sleep disturbance following hospital admission for COVID-19 is associated with dyspnoea, anxiety, and muscle weakness. Due to the association with multiple symptoms, targeting sleep disturbance might be beneficial in treating the post-COVID-19 condition. Funding: UK Research and Innovation, National Institute for Health Research, and Engineering and Physical Sciences Research Council. UK Research and Innovation, National Institute for Health Research, and Engineering and Physical Sciences Research Council.

Data sharing statement This is an Open Access article under the CC BY 4.0 license The ISARIC4C protocol, data sharing and publication policy are available at https://isaric4c.net. ISARIC4C's Independent Data and Material Access Committee welcomes applications for access to data and materials (https://isaric4c.net). The PHOSP-COVID protocol, consent form, definition and derivation of clinical characteristics and outcomes, training materials, regulatory documents, information about requests for data access, and other relevant study materials are available online: https://phosp.org/resource/. Access to these materials can be granted by contacting phosp@leicester.ac.uk and Phospcontracts@leicester.ac.uk. All data used in this study is available within ODAP and accessible under reasonable request. Data access criteria and information about how to request access is available online: https://phosp.org/resource/. If criteria are met and a request is made, access can be gained by signing the eDRIS user agreement. Supplementary data are available online at https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(22)00584-9/fulltext#supplementaryMaterial . Copyright © 2022 The Author(s). Background: Most studies of immunity to SARS-CoV-2 focus on circulating antibody, giving limited insights into mucosal defences that prevent viral replication and onward transmission. We studied nasal and plasma antibody responses one year after hospitalisation for COVID-19, including a period when SARS-CoV-2 vaccination was introduced. Methods: In this follow up study, plasma and nasosorption samples were prospectively collected from 446 adults hospitalised for COVID-19 between February 2020 and March 2021 via the ISARIC4C and PHOSP-COVID consortia. IgA and IgG responses to NP and S of ancestral SARS-CoV-2, Delta and Omicron (BA.1) variants were measured by electrochemiluminescence and compared with plasma neutralisation data. Findings: Strong and consistent nasal anti-NP and anti-S IgA responses were demonstrated, which remained elevated for nine months (p < 0.0001). Nasal and plasma anti-S IgG remained elevated for at least 12 months (p < 0.0001) with plasma neutralising titres that were raised against all variants compared to controls (p < 0.0001). Of 323 with complete data, 307 were vaccinated between 6 and 12 months; coinciding with rises in nasal and plasma IgA and IgG anti-S titres for all SARS-CoV-2 variants, although the change in nasal IgA was minimal (1.46-fold change after 10 months, p = 0.011) and the median remained below the positive threshold determined by pre-pandemic controls. Samples 12 months after admission showed no association between nasal IgA and plasma IgG anti-S responses (R = 0.05, p = 0.18), indicating that nasal IgA responses are distinct from those in plasma and minimally boosted by vaccination. Interpretation: The decline in nasal IgA responses 9 months after infection and minimal impact of subsequent vaccination may explain the lack of long-lasting nasal defence against reinfection and the limited effects of vaccination on transmission. These findings highlight the need to develop vaccines that enhance nasal immunity. Funding: This study has been supported by ISARIC4C and PHOSP-COVID consortia. ISARIC4C is supported by grants from the National Institute for Health and Care Research and the Medical Research Council. Liverpool Experimental Cancer Medicine Centre provided infrastructure support for this research. The PHOSP-COVD study is jointly funded by UK Research and Innovation and National Institute of Health and Care Research. The funders were not involved in the study design, interpretation of data or the writing of this manuscript. This work is supported by the following grants: The PHOSP-COVD study is jointly funded by UK Research and Innovation and National Institute for Health and Care Research (grant references: MR/V027859/1 and COV0319). ISARIC4C is supported by grants from the National Institute for Health and Care Research (award CO-CIN-01) and the Medical Research Council (grant MC_PC_19059) Liverpool Experimental Cancer Medicine Centre provided infrastructure support for this research (grant reference: C18616/A25153). Other grants which have supported this work include: the UK Coronavirus Immunology Consortium [funder reference:1257927], the Imperial Biomedical Research Centre (NIHR Imperial BRC, grant IS-BRC-1215-20013), the Health Protection Research Unit (HPRU) in Respiratory Infections at Imperial College London and NIHR HPRU in Emerging and Zoonotic Infections at University of Liverpool, both in partnership with Public Health England, [NIHR award 200907], Wellcome Trust and Department for International Development [215091/Z/18/Z], Health Data Research UK (HDR UK) [grant code: 2021.0155], Medical Research Council [grant code: MC_UU_12014/12], and NIHR Clinical Research Network for providing infrastructure support for this research. FL is supported by an MRC clinical training fellowship [award MR/W000970/1]. LPH is supported by Oxford NIHR Biomedical Research Centre. AART is supported by a BHF Intermediate Clinical Fellowship (FS/18/13/33281). SLRJ receives support from UKRI, GCRF, Rosetrees Trust, BHIVA, EDCTP, Globvac. JDC has grants from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Gilead Sciences, Grifols, Novartis and Insmed. RAE holds a NIHR Clinician Scientist Fellowship (CS-2016-16-020). AH is currently supported by UK Research and Innovation. NIHR and NIHR Manchester BRC. BR receives support from BHF Oxford Centre of Research Excellence, NIHR Oxford BRC and MRC. SJD is funded by an NIHR Global Research Professorship [NIHR300791]. DW is supported by an NIHR Advanced Fellowship. AH has received support from MRC and the Coronavirus Immunology Consortium (MR/V028448/1). LVW has received support from UKRI, GSK/Asthma + Lung UK and NIHR for this study. MGS has received support from NIHR UK, MRC UK and Health Protection Research Unit in Emerging & Zoonotic Infections, University of Liverpool. JKB is supported by the Wellcome Trust (223164/Z/21/Z) and UKRI (MC_PC_20004, MC_PC_19025, MC_PC_1905, MRNO2995X/1, and MC_PC_20029). PJMO is supported by a NIHR Senior Investigator Award [award 201385]. LT is supported by the Wellcome Trust [clinical career development fellowship grant number 205228/Z/16/Z], the Centre of Excellence in Infectious Diseases Research (CEIDR) and the Alder Hey Charity.

When people think about hazards, the types that easily come to their mind include natural hazards, such as earthquakes, tornados, and tsunamis, and manmade ones, such as plane crashes, bomb explosions, and exposure to toxic industrial chemicals. Disease outbreaks are a source of hazards that are often overlooked, and the largely forgotten smallpox was an example of such disease. This article provides a review of the emergency management practices that curtailed the potentially devastating spread of smallpox at Meschede, Germany in 1970. Lessons that can be transferred to the COVID-19 pandemic are also discussed.

A 64-year-old man presented with painless sequential bilateral vision loss, consistent with optic neuropathy, over the span of months. The significant decline in his visual function was out of proportion to the appearance of the optic nerves (which were not pale) or changes in his retinal nerve fiber layer thickness on optical coherence tomography. Neuroimaging revealed only mild T2 signal abnormality and faint enhancement in the left optic nerve. Extensive workup for potential infectious, metabolic, inflammatory, and ischemic etiologies was unremarkable. Empiric treatment with intravenous steroids did not slow or ameliorate the vision loss. Ultimately, genetic analysis revealed a missense m.11778Ggt;A mutation in mitochondrial MT-ND4 gene, consistent with Leber hereditary optic neuropathy. Initiation of multivitamin supplements and idebenone unfortunately did not result in recovery of vision.

Lassa fever is a disease that is not well-known worldwide, particularly due to the inability of the multimammate rat, the primary vector of the Lassa virus, to breed in temperate regions. The aim of this review is to provide an overview of the disease and its modus operandi while also providing information about trends in the past decade, as well as proven strategies that have been used to manage its spread.

Data sharing statement: PHOSP-COVID: The protocol, consent form, definition and derivation of clinical characteristics and outcomes, training materials, regulatory documents, requests for data access and other relevant study materials are available online at https://www.phosp.org. COVIDENCE UK: De-identified participant data will be made available upon reasonable request to the corresponding author. Supplementary data is available online at: https://www.sciencedirect.com/science/article/pii/S2666776223000546?via%3Dihub#appsec1 . Copyright © 2023 The Author(s). Background: The risk factors for recovery from COVID-19 dyspnoea are poorly understood. We investigated determinants of recovery from dyspnoea in adults with COVID-19 and compared these to determinants of recovery from non-COVID-19 dyspnoea. Methods: We used data from two prospective cohort studies: PHOSP-COVID (patients hospitalised between March 2020 and April 2021 with COVID-19) and COVIDENCE UK (community cohort studied over the same time period). PHOSP-COVID data were collected during hospitalisation and at 5-month and 1-year follow-up visits. COVIDENCE UK data were obtained through baseline and monthly online questionnaires. Dyspnoea was measured in both cohorts with the Medical Research Council Dyspnoea Scale. We used multivariable logistic regression to identify determinants associated with a reduction in dyspnoea between 5-month and 1-year follow-up. Findings: We included 990 PHOSP-COVID and 3309 COVIDENCE UK participants. We observed higher odds of improvement between 5-month and 1-year follow-up among PHOSP-COVID participants who were younger (odds ratio 1.02 per year, 95% CI 1.01–1.03), male (1.54, 1.16–2.04), neither obese nor severely obese (1.82, 1.06–3.13 and 4.19, 2.14–8.19, respectively), had no pre-existing anxiety or depression (1.56, 1.09–2.22) or cardiovascular disease (1.33, 1.00–1.79), and shorter hospital admission (1.01 per day, 1.00–1.02). Similar associations were found in those recovering from non-COVID-19 dyspnoea, excluding age (and length of hospital admission). Interpretation: Factors associated with dyspnoea recovery at 1-year post-discharge among patients hospitalised with COVID-19 were similar to those among community controls without COVID-19. Funding: PHOSP-COVID is supported by a grant from the MRC-UK Research and Innovation and the Department of Health and Social Care through the National Institute for Health Research (NIHR) rapid response panel to tackle COVID-19. The views expressed in the publication are those of the author(s) and not necessarily those of the National Health Service (NHS), the NIHR or the Department of Health and Social Care. COVIDENCE UK is supported by the UK Research and Innovation, the National Institute for Health Research, and Barts Charity. The views expressed are those of the authors and not necessarily those of the funders. PHOSP-COVID: This study would not be possible without all the participants who have given their time and support. We thank all the participants and their families. We thank the many research administrators, health-care and social-care professionals who contributed to setting up and delivering the study at all of the 65 NHS trusts/Health boards and 25 research institutions across the UK, as well as all the supporting staff at the NIHR Clinical Research Network, Health Research Authority, Research Ethics Committee, Department of Health and Social Care, Public Health Scotland, and Public Health England, and support from the ISARIC Coronavirus Clinical Characterisation Consortium. We thank Kate Holmes at the NIHR Office for Clinical Research Infrastructure (NOCRI) for her support in coordinating the charities group. The PHOSP-COVID industry framework was formed to provide advice and support in commercial discussions, and we thank the Association of the British Pharmaceutical Industry as well NOCRI for coordinating this. We are very grateful to all the charities that have provided insight to the study: Action Pulmonary Fibrosis, Alzheimer's Research UK, Asthma + Lung UK, British Heart Foundation, Diabetes UK, Cystic Fibrosis Trust, Kidney Research UK, MQ Mental Health, Muscular Dystrophy UK, Stroke Association Blood Cancer UK, McPin Foundations, and Versus Arthritis. We thank the NIHR Leicester Biomedical Research Centre patient and public involvement group and Long Covid Support. COVIDENCE UK: We thank all participants of COVIDENCE UK, and the following organisations who supported study recruitment: Asthma UK/British Lung Foundation, the British Heart Foundation, the British Obesity Society, Cancer Research UK, Diabetes UK, Future Publishing, Kidney Care UK, Kidney Wales, Mumsnet, the National Kidney Federation, the National Rheumatoid Arthritis Society, the North West London Health Research Register (DISCOVER), Primary Immunodeficiency UK, the Race Equality Foundation, SWM Health, the Terence Higgins Trust, and Vasculitis UK.

The visual system uses ON and OFF pathways to signal luminance increments and decrements. Increasing evidence suggests that ON and OFF pathways have different signaling properties and serve specialized visual functions. However, it is still unclear the contribution of ON and OFF pathways to visual behavior. Therefore, we examined the effects on optomotor response and the retinal dopamine system in nob mice with ON pathway dysfunction and Vsx1(−/−) mice with partial OFF pathway dysfunction. Spatial frequency and contrast sensitivity thresholds were determined, and values were compared to age-matched wild-type controls. Retinas were collected immediately after visual testing to measure levels of dopamine and its metabolite, DOPAC. At 4 weeks of age, we found that nob mice had significantly reduced spatial frequency (19%) and contrast sensitivity (60%) thresholds compared to wild-type mice. Vsx1(−/−) mice also exhibited reductions in optomotor responses (3% in spatial frequency; 18% in contrast sensitivity) at 4 weeks, although these changes were significantly smaller than those found in nob mice. Furthermore, nob mice had significantly lower DOPAC levels (53%) and dopamine turnover (41%) compared to controls while Vsx1(−/−) mice displayed a transient increase in DOPAC levels at 4 weeks of age (55%). Our results show that dysfunction of ON pathways leads to reductions in contrast sensitivity, spatial frequency threshold, and retinal dopamine and DOPAC levels whereas partial loss of the OFF pathway has minimal effect. We conclude that ON pathways play a critical role in visual reflexes and retinal dopamine signaling, highlighting a potential association for future investigations.

IntroductionPrevention of nosocomial transmission was a priority for NHS hospital teams during the SARS-COV-2 pandemic. However, infection control policies were developed in the face of uncertainty about duration of infectivity, routes of transmission, and safety of shared admission spaces. We retrospectively reviewed all hospital admissions to the University Hospitals of Leicester (UHL) respiratory department, which managed more than 30% of UHL patients with a diagnosis of COVID-19 between March 2020 and March 2021to determine the proportion of cases with laboratory evidence of healthcare associated infection (HCAI) and mortality within 28 days of PCR conversionMethodsThis was a retrospective cohort study performed using a bespoke database collating COVID-19 throat swab (TS) PCR results for UHL (COVTRACK). Nosocomial transmission was identified by demonstrating PCR conversions during admission and categorized into definite (conversion time > 14 days) or probable (conversion time 8–14 days). In depth records based analysis was undertaken for patients admitted to respiratory medicine (RM) and deceased within 28 days after conversion.ResultsOut of 10485 patients admitted to the Respiratory Department at UHL, 2054 (19.6%) were COVID-19 spell positive, including 57 with probable (41) or definite HCAI (16). 23 patients (7 with definite HCAI) died within 28 days of PCR conversion (0.22%, of total admitted, 1.1% of COVID19 positive), with 21 (91%) deaths in the 2nd wave. Compared with non-COVID admissions not acquiring nosocomial infection, HCAI was significantly associated with older age (mean difference (95%CI) 11.5 (7.5–15.5) years), length of stay (median LOS 18 Vs 1 day) and multiple ward occupancy (median 3 vs 1 ward);all analyses p

Purpose: Previous studies demonstrated that systemic treatment with tauroursodeoxycholic acid (TUDCA) is protective in in vivo mouse models of retinal degeneration and in culture models of hyperglycemia. This study tested the hypothesis that TUDCA will preserve visual and retinal function in a mouse model of early diabetic retinopathy (DR). Methods: Adult C57BL/6J mice were treated with streptozotocin (STZ) and made diabetic at 8–10 weeks of age. Control and diabetic mice were treated with vehicle or TUDCA starting 1 or 3 weeks after induction of diabetes, and were assessed bimonthly for visual function via an optomotor response and monthly for retinal function via scotopic electroretinograms. Results: Diabetic mice showed significantly reduced spatial frequency and contrast sensitivity thresholds compared to control mice, while diabetic mice treated early with TUDCA showed preservation at all timepoints. A-wave, b-wave, and oscillatory potential 2 (OP2) amplitudes decreased in diabetic mice. Diabetic mice also exhibited delays in a-wave and OP2-implicit times. Early TUDCA treatment ameliorated a-wave, b-wave, and OP2 deficits. Late TUDCA treatment showed reduced preservation effects compared to early treatment. Conclusions: Early TUDCA treatment preserved visual function in an STZ-mouse model of Type I diabetes. These data add to a growing body of preclinical research that may support testing whether TUDCA may be an effective early clinical intervention against declining visual function caused by diabetic retinopathy.

Several months into the coronavirus disease 2019 (COVID-19) pandemic, there is growing concern over an increase in the incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-linked Kawasaki-like disease in the pediatric population. The pediatric patients presented to the emergency room with impending shock in the setting of an atypical Kawasaki picture. On May 14, 2020, the CDC Health Alert Network released a case definition for this evolving syndrome and named it multi-system inflammatory syndrome in children (MIS-C). We report three cases of MIS-C associated with SAR-COV2 who presented to our emergency room. Persistent fever was present in all three patients and mucocutaneous and gastrointestinal symptoms were the most common associations. All three patients were found to have antibodies to COVID-19. MIS-C is a similar but distinct entity as compared to Kawasaki disease. High inflammatory markers are supportive of the diagnosis, and cardiac evaluation is crucial in MIS-C. High suspicion for the diagnosis and low threshold for workup will prevent delayed treatment.

Introduction Alzheimer’s disease is associated with low bone mineral density. Various studies have linked early-onset Alzheimer's disease with bone health. In this study, we will determine the association between bone health and recently diagnosed Alzheimer's disease in the local population. Methods This case-control study was conducted at the neurology unit from April 2019 to Sept 2019. One hundred and fifty (150) Alzheimer’s patients with recently (within the last six months) confirmed diagnoses, based on clinical symptoms, mental status, and computed tomography (CT) scan, were included from the neurology outpatient department. The gender and age-matched 150 healthy participants were included in the study as the reference group. Various parameters of bone health and mental status were measured. Results Participants with Alzheimer’s had a significantly lower level of serum vitamin D (15.2 ± 4.2 ng/mL vs. 27.5 ± 8.1 ng/mL, p-value: < 0.0001) and lower level of serum osteocalcin (4.3 ± 1.7 ng/L vs. 5.6 ± 2.0 ng/L, p-value: < 0.0001). Participants with Alzheimer’s disease had more people with T-score ≤ -2.5 as compared to the general population (52.0% vs. 16.6%, p-value

Introduction: Leptin, a satiety hormone, has the ability to inhibit hunger and is thus, a regulator of body weight. Leptin is also elevated in cardiovascular events such as acute myocardial infarction (AMI) and hence is considered as modifiable risk factors for AMI. The purpose of this study is therefore to investigate the correlation of leptin with AMI. Methodology: In this retrospective study, data of patients were taken from the database between January 2017 to December 2019 from a cardiovascular unit of tertiary care hospital in Pakistan. Patients were divided into two groups, based on participants who had suffered from AMI and other groups who had not suffered an AMI. Leptin levels were compared for both groups. Age, body mass index (BMI), and smoking history were noted in a self-structured questionnaire. In addition, mean blood pressure and cholesterol levels were also noted for both groups. Results: Leptin was significantly higher in patients with first time AMI (29.21 ± 9.21 ng/mL vs. 11.23 ± 3.12 ng/mL: p-value

Introduction Stress is a phenomenon elicited in response to certain triggers that may be external or internal. Stress has been identified as a risk factor for various diseases, including cardiovascular disease. In this study, we aim to find an association between psychological stress and cardiovascular disease in the local setting Methods This case-control study was conducted in a tertiary care hospital in Pakistan from June 2019 to December 2019. One hundred and seventeen (117) patients with myocardial infarction and unstable angina were enrolled in the case group. One hundred and ten (110) patient's attendants were enrolled in the study as controlled. Results The risk of a cardiovascular event was higher in patients with a history of social isolation (OR, 2.47), marital stress (OR, 2.28), work stress (OR, 3.2), childhood abuse (OR, 2.78), or trauma (OR, 2.67). Conclusion Psychological stress is an important risk for cardiovascular disease, which is often overlooked. Efforts should be made to include questions related to psychological stress in the history-taking of patients at risk of a cardiovascular event and the management plan should include psychological counseling.

Setting Several projects involving accelerated or active case finding (ACF) of tuberculosis (TB) cases are being implemented in Myanmar. However, there is a concern that patients detected using ACF have poorer TB treatment outcomes than those detected using passive case finding (PCF). Objective To assess differences in the demographics, clinical profile and treatment outcomes of patients detected using ACF and PCF. Design Retrospective cohort study of TB patients diagnosed and enrolled for treatment during 2014-2016. Results Of 16 048 patients enrolled, 2226 (16%) were detected using ACF; the treatment success rate (cured and completed) was 88%. A higher proportion of cases detected using ACF were aged 55 years, human immunodeficiency virus (HIV) negative and sputum smear-positive pulmonary TB. After adjusting for differences in demographic and clinical characteristics, we found that treatment outcomes in patients detected using ACF and PCF were not significantly different (adjusted relative risk [aRR] 0.89, 95%CI 0.78-1.00). Male sex, age  55 years, patients with a previous history of TB and HIV positivity were independently associated with unsuccessful outcomes. Conclusion ACF detected a significant proportion of TB cases in study townships; treatment outcomes in cases detected using ACF and those detected using PCF were similar. More tailored interventions are needed to improve treatment outcomes in patients at a higher risk of unsuccessful treatment outcomes.

What is spirituality? There have been and will continue to be so many differential definitions and explanations regarding this vitally important concept and questions over our present, past and future seconds, minutes, hours, days, weeks, months, years, centuries and millennia and there is no way to fully and finally document these heartfelt endeavors right here and right now as indicated in this present installation.

Background In a wide range of industries, noise-induced hearing loss remains one of the most prevalent occupational problems. This study aimed to assess the noise exposure level and associated factors of hearing loss among textile workers in Yangon Region, Myanmar. Methods A cross-sectional study was conducted at a Textile mill (Thamine), Yangon Region, from April to December 2018. In total, 226 workers who were randomly selected from 3 weaving sections participated in face-to-face interviews using a structured questionnaire. A digital sound level meter and pure-tone audiometer were used for the assessment of noise exposure level and hearing loss, respectively. Logistic regression analysis was performed to assess the associated factors of hearing loss. Results In total workers, 66.4% were exposed to ≥85 dB(A) of noise exposure, and the prevalence of hearing loss was 25.7%. Age ≥35 years, below high school education, hearing difficulty, tinnitus, hypertension, > 9 years of service duration in a textile mill were positively associated with hearing loss. After adjusting confounding factors, age ≥35 years (adjusted odds ratio = 6.90, 95% confidence interval = 3.45-13.82) and tinnitus (adjusted odds ratio = 2.88, 95% confidence interval = 1.13-7.37) were persistently associated with hearing loss. Conclusion Providing occupational hazard education and enforcement of occupational safety regulations should be taken to decrease the noise exposure level. The regular audiometry test should be conducted for assessment of hearing threshold shift. The employer needs to implement a hearing conservation program in workplace when noise exposure reaches or exceeds 85 dB(A) for 8 hours.

The purpose of this study was to determine the efficacy of a Peruvian botanical formulation for treating disorders of hepatic function and gastric mucosal integrity. The formulation A4+ (Sabell Corporation) contains extracts of Curcuma longa rhizome, Cordia lutea flower, and Annona muricata leaf. Individually these plants have been used as traditional remedies for liver disease. We report the efficacy of A4+ and its components using a variety of in vitro and in vivo disease models. The methods used included tests for antioxidant, anti-inflammatory, and antiviral activity as well as mouse models of liver disease, including Concanavalin A-induced immune-mediated hepatitis and a bile duct ligation model for evaluating sickness behaviour associated with liver disease. Rat models were used to evaluate the gastric mucosal protective property of A4+ following indomethacin challenge and to evaluate its anti-inflammatory action in an “air pouch” model. In all tests, A4+ proved to be more effective than placebo. A4+ was antioxidant and anti-inflammatory and diminished Hepatitis C virus replication in vitro. In animal models, A4+ was shown to protect the liver from immune-mediated hepatitis, improve behavioural function in animals with late stage liver disease, and protect the rat gastric mucosa from ulceration following NSAID exposure. We conclude that A4+ ameliorated many aspects of liver injury, inhibited hepatitis C virus replication, and protected the gastric mucosa from NSAIDs. These varied beneficial properties appear to result from positive interactions between the three constituent herbs.

There is a paradigm-shift in the workplace from a production mentality to a service-oriented mentality. As a result, there is a greater need on employees to expend emotional labor in dealing with the challenges of meeting the demands of a service-oriented economy. This present study discussed the impact that expending emotional labor has on the health of employees in the workplace. Literature was retrieved from MEDLINE/PubMed, Excerpta Medica/EMBASE, Scopus and Thomson Reuters’ Web of Science databases. Studies were selected if they were published between 2013 and 2018, written in English and had the terms “emotional labor” or “emotional labour” in their titles. An overview of the different effects of emotional labor on the health of employees in different sectors of the economy revealed effects ranging from burnout and fatigue to dysmenorrhea, disruptions in sleep patterns and suicidal tendencies. The effects of emotional labor on the health of members of the population who belong to the working class can be attributed to reciprocal determinism where environmental influences in the form of clients, supervisors, or organizational culture put employees in a position where they had to develop the habit of engaging emotional labor to cope with environmental stresses.

Testing and implementation of Human-Robot Collaboration (HRC) could be dangerous due to the high-speed movements and massive forces generated by industrial robots. Wherever humans and industrial robots share a common workplace, accidents are likely to happen and always unpredictable. This has hindered the development of human robot collaborative strategies as well as the ability of authorities to pass regulations on how humans and robots should work together in close proximities. This paper presents the use of a Virtual Reality digital twin of a physical layout as a mechanism to understand human reactions to both predictable and unpredictable robot motions. A set of established metrics as well as a newly developed Kinetic Energy Ratio metric are used to analyse human reactions and validate the effectiveness of the Virtual Reality environment. It is the aim that Virtual Reality digital twins could inform the safe implementation of Human-Robot Collaborative strategies in factories of the future.

This article will discuss the vital role of body, mind, and spirit in the context of Traditional Chinese Medicine and the treatment of Post-concussion Syndrome (PCS) and Post-traumatic Stress Disorder (PTSD), as proven by practical evidence as a result of Aung Vital Energetic Alignment therapies. It will also discuss the role of the meridian and chakra systems, as well as means for utilizing these systems to improve patients’ quality of life in such contexts. In certain difficult cases, when acupuncture is not invoking a response in patients, other treatment modalities should be considered; namely, the treatment modality of Aung Vital Energetic Alignment. In this article, Dr. Aung describes how he discovered the role of treating the body, mind, and spirit as a practitioner and how firsthand experience in treating all aspects of personhood has resulted in his self-discovery of realignment therapies. This chapter discusses alternative treatment modalities for PCS and PTSD using Aung Vital Energetic Alignment acupuncture (i.e. AVEA protocol). It will also discuss natural forms of therapy, such as tree-hugging, which provides natural realignment, as well as the utilization of seven chakra phonation, concentration, meditation and Qi Gong exercises as a means for addressing PCS and PTSD. This chapter will also describe treatment modalities for addressing pediatric and neonatal malalignments via acu-touch treatments to ensure the well-being, intelligence and intuitional progression in infants for preventative purposes. Starting from infancy, correctly-aligned pediatric patients will mature influence society as individuals who display optimal intellectual and intuitive health, so as to be a positive and productive force in the universe.

Diabetic retinopathy is a leading cause of vision loss. Treatment options for early retinopathy are sparse. Exercise protects dying photoreceptors in models of retinal degeneration, thereby preserving vision. We tested the protective effects of exercise on retinal and cognitive deficits in a type 1 diabetes model and determined whether the TrkB pathway mediates this effect. Hyperglycaemia was induced in Long Evans rats via streptozotocin injection (STZ; 100 mg/kg). Following confirmed hyperglycaemia, both control and diabetic rats underwent treadmill exercise for 30 min, 5 days/week at 0 m/min (inactive groups) or 15 m/min (active groups) for 8 weeks. A TrkB receptor antagonist (ANA-12), or vehicle, was injected 2.5 h before exercise training. We measured spatial frequency and contrast sensitivity using optokinetic tracking biweekly post-STZ; retinal function using electroretinography at 4 and 8 weeks; and cognitive function and exploratory behaviour using Y-maze at 8 weeks. Retinal neurotrophin-4 was measured using ELISA. Compared with non-diabetic controls, diabetic rats showed significantly reduced spatial frequency and contrast sensitivity, delayed electroretinogram oscillatory potential and flicker implicit times and reduced cognitive function and exploratory behaviour. Exercise interventions significantly delayed the appearance of all deficits, except for exploratory behaviour. Treatment with ANA-12 significantly reduced this protection, suggesting a TrkB-mediated mechanism. Despite this, no changes in retinal neurotrohin-4 were observed with diabetes or exercise. Exercise protected against early visual and cognitive dysfunction in diabetic rats, suggesting that exercise interventions started after hyperglycaemia diagnosis may be a beneficial treatment. The translational potential is high, given that exercise treatment is non-invasive, patient controlled and inexpensive.

Visual experience during the critical period modulates visual development such that deprivation causes visual impairments while stimulation induces enhancements. This study aimed to determine whether visual stimulation in the form of daily optomotor response (OMR) testing during the mouse critical period (1) improves aspects of visual function, (2) involves retinal mechanisms and (3) is mediated by brain derived neurotrophic factor (BDNF) and dopamine (DA) signaling pathways. We tested spatial frequency thresholds in C57BL/6J mice daily from postnatal days 16 to 23 (P16 to P23) using OMR testing. Daily OMR-treated mice were compared to littermate controls that were placed in the OMR chamber without moving gratings. Contrast sensitivity thresholds, electroretinograms (ERGs), visual evoked potentials, and pattern ERGs were acquired at P21. To determine the role of BDNF signaling, a TrkB receptor antagonist (ANA-12) was systemically injected 2 hours prior to OMR testing in another cohort of mice. BDNF immunohistochemistry was performed on retina and brain sections. Retinal DA levels were measured using high-performance liquid chromatography. Daily OMR testing enhanced spatial frequency thresholds and contrast sensitivity compared to controls. OMR-treated mice also had improved rod-driven ERG oscillatory potential response times, greater BDNF immunoreactivity in the retinal ganglion cell layer, and increased retinal DA content compared to controls. VEPs and pattern ERGs were unchanged. Systemic delivery of ANA-12 attenuated OMR-induced visual enhancements. Daily OMR testing during the critical period leads to general visual function improvements accompanied by increased DA and BDNF in the retina, with this process being requisitely mediated by TrkB activation. These results suggest that novel combination therapies involving visual stimulation and using both behavioral and molecular approaches may benefit degenerative retinal diseases or amblyopia.

Purpose Electroretinograms (ERGs) are abnormal in diabetic retinas before the appearance of vascular lesions, providing a possible biomarker for diabetic vision loss. Previously, we reported that decreased retinal dopamine (DA) levels in diabetic rodents contributed to early visual and retinal dysfunction. In the current study, we examined whether oscillatory potentials (OPs) could serve as a potential marker for detecting early inner retinal dysfunction due to retinal DA deficiency. Methods Retinal function was tested with dark-adapted ERGs, taken at 3, 4, and 5 weeks after diabetes induction with streptozotocin. Electrical responses were analyzed and correlations were made with previously reported retinal DA levels. The effect of restoring systemic DA levels or removing DA from the retina in diabetic mice on OPs was assessed using L-3,4-dihydroxyphenylalanine (L-DOPA) treatments and retina-specific tyrosine hydroxylase (Th) knockout mice (rTHKO), respectively. Results Diabetic animals had significantly delayed OPs compared to control animals in response to dim, but not bright, flash stimuli. L-DOPA treatment preserved OP implicit time in diabetic mice. Diabetic rTHKO mice had further delayed OPs compared to diabetic mice with normal retinal Th, with L-DOPA treatment also providing benefit. Decreasing retinal DA levels significantly correlated with increasing OP delays mediated by rod pathways. Conclusions Our data suggest that inner retinal dysfunction in early-stage diabetes is mediated by rod-pathway deficits and DA deficiencies. OP delays may be used to determine the earliest functional deficits in diabetic retinopathy and to establish an early treatment window for DA therapies that may prevent progressive vision loss.

Molecular nutrition is relatively recent research discipline that aims to decipher molecular effects of nutrition at the cellular level and identify mechanisms underlying potential impact on health, protective or deleterious. The development and the use of holistic “omics” approach in the last decade or two have revealed the complexity of action of different nutrients at the molecular level. These nutrigenomic studies have shown that nutrients can impact transcriptional and post transcriptional regulation of gene expression, by impacting expression of mRNA, non-coding RNAs (both short and long) and proteins, but also modulate epigenetic profile of the cells. The capacity of nutrients to exert these nutrigenomic effects can be related to the their ability to bind to cell signaling proteins, modulate their activity and consequently that of transcription factors. The feature article gives a rapid overview of molecular mechanisms impacted by different nutrients.

During the Sino-Japanese conflict of the 1920s, Japanese botanist Ichiro Ohga was presented single-seeded fruit of Nelumbo nucifera var. China Antique collected by a local farmer from a dry lakebed in Northeast China (then, “Manchuria”). Ohga studied the fruit and published his findings. Years later, we tested the germination of Nelumbo fruit from the same locality. The oldest seed sprouted, having a germination time of ~3 days, was radiocarbon dated to be ~1300 years old. These cold- and drought-tolerant seeds exhibited shoot-before-root emergence and a primary green plumule capable of “dim-light” photosynthesis. Such traits and the notable long-term viability of the fruit spurred the interest of Ray Ming, University of Illinois that has now led to the sequencing of the Nelumbo genome. Analyses of this genome may provide insight into the biochemistry of Nelumbo on wax-biosynthesis genes, and application of aging-related thermostable proteins to the extension of seed-life and improvement of food quality of economic crops. Here, we review the history of these long-lived Nelumbo fruit, and their occurrence, discovery, collection, propagation, and methods of seedling care. The robust impermeable wax- and suberin-covered pericarp is a major factor contributing to their remarkable longevity. New findings are presented on the modern and 459- and 464-year-old pericarp anatomy, impermeability to water, and whole fruit and pericarp mechanical properties, and comparison of the mode of fruit weight-gain during imbibition and germination time relative to fruit maturity.

Reactive oxygen species (ROS) can induce oxidative injury via iron interactions (i.e. Fenton chemistry and hydroxyl radical formation). Our prior work suggested that American ginseng berry extract and ginsenoside Re were highly cardioprotective against oxidant stress. To extend this study, we evaluated the protective effect of protopanaxadiol-type ginsenoside Rb1 (gRb1) on H(2)O(2)-induced oxidative injury in cardiomyocytes and explored the ROS-mediated intracellular signaling mechanism. Cultured embryonic chick cardiomyocytes (4-5 day) were used. Cell death was assessed by propidium iodide and lactate dehydrogenase release. Pretreatment with gRb1 (0.01, 0.1, or 1 μM) for 2 h and concurrent treatment with H(2)O(2) (0.5 mM) for 2 h resulted in a dose-dependent reduction of cell death, 36.6 ± 2.9% (n = 12, p0.05), 30.5 ± 5.1% (n = 12, p0.05) and 28.6 ± 3.1% (n = 12, p0.01) respectively, compared to H(2)O(2)-exposed cells (48.2 ± 3.3%, n = 12). This cardioprotective effect of gRb1 was associated with attenuated intracellular ROS generation as measured by 6-carboxy-2', 7'-dichlorodihydrofluorescein diacetate, preserved the mitochondrial membrane potential as determined using JC-1. In the ESR study, gRb1 exhibited the scavenging DPPH and hydroxyl radical activities. Furthermore, our data showed the increased JNK phosphorylation (p-JNK) in H(2)O(2)-exposed cells was suppressed by the pretreatment with gRb 1 (1 μM) (p0.01). Co-treatment of gRb1 with a specific inhibitor of JNK SP600125 (10 μM) further reduced the p-JNK and enhanced the cell survival after H(2)O(2) exposure. Collectively, our results suggest that gRb1 conferred cardioprotection that was mediated via attenuating ROS and suppressing ROS-induced JNK activation.

Oplopanax horridus or devil’s club is a herbal medicine distributed in North America. The constituents and pharmacological activities of O. horridus (OPH) are largely unknown. In this study, we assayed OPH stem and berry extracts using high performance liquid chromatography (HPLC). The anticancer potentials of extracts on different human cancer cell lines (SW-480, HCT-116, HT-29, MCF-7 and NSCLC) were determined by MTS method. The effect of stem extract on cancer cell cycle, expression of cyclin A, and apoptosis were assayed using flow cytometry. HPLC data showed that the composition of OPH stem extract is more complicated than the berry extract. The wavelength of maximum absorption of the major constituent in stem and berry is 196.0 nm and 201.9 nm, respectively. Compared to the berry extract, the stem extract showed significant potent antiproliferative effect on all the studied cell lines. The stem extract at 0.1 mg/ml arrested cancer cells in S- and G2/M-phases, and significantly induced expression of cyclin A. After treatment with 0.1 mg/ml of stem extract for 72 h, apoptotic cells were increased to 45.2%, while control was 9.6%. The cell cycle arrest and induction of apoptosis may play a critical role in cancer chemoprevention by Oplopanax horridus stem extract.

This study aims to identify the wave characteristics in Sabah waters to compare its characteristics at five different waters and to determine the effects of the Northeast monsoon (NEM) and Southwest monsoon (SWM) to the east coast and west coast of Sabah waters. Monthly wave observation data of wave height, wave period and wave power between 1991 to 1998 covering areas waters off Labuan, Kota Kinabalu, Kudat, Sandakan and Tawau was collected from the Meteorological Department. The wave height and wave period were analysed directly from the data provided while wave power was calculated according to the wave power equation. The wave data at different area were analysed through the probability density function (p.d.t) and the cumulative probability density function (c.p.d.t). The range of wave heights in coastal waters surrounding Sabah is found to be between 0.5 m to 2 m. Both wave characteristics in Sandakan and Tawau waters appeared to have similar trend compared to that in Labuan, Kota Kinabalu and Kudat. Higher ranged wave heights and wave power occurred in the west coast of Sabah during the NEM. However, the wave period is almost the same for the east coast and west coast during both monsoonal seasons. The findings of this study will be useful for navigation purpose and coastal zone management activities.

Problem statement: A widely held belief that climate change has impacts on sustainable fish catch leads us to find out how these effects influence fish landings in Sabah, Malaysia, especially for the west and east coasts, based upon monsoonal periods. Correlation of fish landings with rainfall suggests that local fish landing is believed to be sensitive to the effects of climate change. Approach: Rainfall, temperature, wind, the Southern Oscillation Index (SOI) and fish landings time series for 3 specific regions (Kota Kinabalu (KK), Tawau and Sandakan) have been studied using available local data for the last 9 years. Results: Results indicated significant fish landing variations due to the fluctuation of these meteorological parameters, for example, ~20% reduction is found during Northeast (NE) monsoon at KK. Heavy rainfall correlates well with high fish landings when fish landings lead rainfall by 1 month. Fish landings and temperature were also highly correlated. Fish landings leads wind stress by 1-2 months with 99% certainty and it is high when the wind direction is between 150-200° from north (approximately for South Easterlies and South Westerlies). Conclusion: The results confirmed that fish landing is low during NE monsoon period. In regard to the effect of El Nino Southern Oscillation (ENSO), low or negative SOI indicates high fish landings.

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