Thrombosis in VEXAS syndrome.

VEXAS syndrome, an autoinflammatory syndrome due to a Ubiquitin Like Modifier Activating Enzyme 1 (UBA1) somatic mutation, has a high thrombotic burden. We report a case of a 69-year-old male that was diagnosed with VEXAS syndrome who developed venous thromboembolism (VTE). Review of literature of existing VEXAS syndrome cases showed a high thrombotic burden, with the reported incidence of VTE (36.4%) being markedly higher than arterial thrombosis (1.6%), with deep vein thrombosis being more common than pulmonary embolism. Somatic mutation in the UBA1 gene results in decreased ubiquitylation which is a key driver in the development of thrombosis in VEXAS syndrome, due to chronic inflammation and cytokine release from abnormal crosstalk between the intrinsic effector mechanism of innate immune cells, platelets and endothelium resulting in dysregulated haemostasis and endothelial dysfunction. Targeting endothelial dysfunction and reducing inflammatory milieu causing hypercoagulability with immunosuppressants and immunomodulatory agents, together with anticoagulation may be the strategy to prevent recurrent thrombotic events.

Assessment of respiratory dust exposure and lung functions among workers in textile mill (Thamine), Myanmar: a cross-sectional study.

BACKGROUND: Airborne dusts are being potentially harmful for workers in occupational environment. Exposure to respirable dust is the most important concern in textile workers for the widespread of occupational lung diseases, especially more serious in developing countries. The aim of the study was to assess the respirable dust exposure and associated factors of lung functions among textile workers. METHODS: A cross-sectional study was carried out at a textile mill (Thamine), Yangon Region, from April to December, 2018 and a total of 207 textile workers were randomly selected by using a multistage sampling procedure. Data were collected by using a structured questionnaire for respiratory symptoms, an air sampling pump for assessment of respirable dust exposure, and a spirometer for testing the lung functions. Logistic regression analysis was performed to assess the associated factors of lung functions. Odds ratios with a 95% confidence interval were computed for strength of associations at the significance level of α ≤ 0.05. RESULTS: The mean (± standard deviation, SD) respirable dust exposure was 3.3 mg/m3 (± 0.69) and the prevalence of increased respirable dust exposure (> 3 mg/m3) was 50.7%. The level of respirable dust exposure was highest in the textile workers involving at twisting department. The means (± SD) spirometry values were FVC 82.8% (± 17.8), FEV1 83.6% (± 18.5), and FEV1/FVC 0.9 (± 0.1). Overall magnitude of reduced lung functions was 40.1%, and the prevalence of reduced FVC, FEV1, and FEV1/FVC were 36.7, 34.3 and 3.9% respectively. The current working at twisting department, > 5 years of service duration, respiratory symptoms and increased respirable dust exposure were associated with reduction in FVC and FEV1. CONCLUSIONS: The current working department, service duration, respiratory symptoms and exposure to respirable dust were predictors of lung functions in textile workers. An adequate ventilation, good work practices, hygienic workplace, safety and health training regarding potential health effects, and periodically assessment of lung functions are the critical elements for control of respirable dust exposure and reduction of occupational lung diseases.

Psychometric Cognitive Decline Precedes the Advent of Subjective Cognitive Decline in the Evolution of Alzheimer's Disease.

BACKGROUND: We have described the clinical stages of the brain aging and Alzheimer's disease (AD) continuum. In terms of the pre-dementia stages of AD, we introduced the terminology "mild cognitive impairment" (MCI) for the first pre-dementia stage and "subjective cognitive decline" (SCD) for the pre-MCI stage. We now report the characteristics of a pre-SCD condition eventuating in likely AD. OBJECTIVE: The aim of this study was to characterize a pre-SCD condition eventuating in AD. METHOD: Sixty healthy persons with "no cognitive decline" (NCD) were recruited and 47 were followed (mean baseline age, 64.1 ± 8.9 years; mean follow-up time, 6.7 ± 3.1 years). Outcome was determined at the final assessment prior to 2002 as "decliner," if SCD or worse, or "nondecliner" if NCD. RESULTS: After controlling for age, gender, years of education, and follow-up time, there was a between-group difference in the decline rate (p < 0.001). Also, after controlling for demographic variables and follow-up time, the combinatorial psychometric score was lower at baseline in the future decliners (p = 0.035). Of the 9 psychometric variables, after controlling for demographic variables and follow-up time, 3 were significantly lower at baseline in future decliners. Since AD is known to be age related and all subjects in this study were otherwise healthy, we also did an analysis without controlling for age. The combinatorial psychometric score was highly significantly better at baseline in the future nondecliners than in the future decliners (p = 0.008). CONCLUSION: This is ostensibly the first study to link psychometric cognitive decline to the subsequent SCD stage of eventual AD.

Nitric oxide suppresses aluminum-induced programmed cell death in peanut (Arachis hypoganea L.) root tips by improving mitochondrial physiological properties.

Aluminum (Al) stress alters nitric oxide (NO) and induces programmed cell death (PCD) in plants. Recent study has shown that NO inhibits Al-induced PCD. However, the mechanism of NO inhibiting Al-induced PCD has not been revealed yet. Here, we investigated the behavior of mitochondria during Al-induced PCD suppressed by NO in peanut. Seedlings of peanut was grown hydroponically in a controllable growth room. The mitochondrial physiological parameters were determined spectrophotometrically. The expression of AhANT and AhHsp70 was determined by quantitative RT-PCR. Al-induced cell death rapidly in peanut root tips is mitochondria-dependent PCD. There was a significantly negative relationship between PCD and mitochondrial NO/H2O2 level. Compared with Al treatment alone, the addition of NO donor sodium nitroprusside (SNP) increased the ratio of NO/H2O2, down-regulated AhANT expression and inhibited the opening of mitochondrial permeability transition pore (MPTP), up-regulated AhHsp70 expression and increased mitochondrial inner membrane potential (ΔΨm), reduced cytochrome c (Cyt c) release from mitochondria and caspase 3-like protease activity, while the effect of NO specific scavenger cPTIO supplement was opposite. NO suppresses Al-induce PCD in peanut root tips by improving mitochondrial physiological properties.

Adherence to COVID-19 preventive measures among residents in selected townships, Yangon Region, Myanmar: a community-based cross-sectional study.

BACKGROUND: To fight the current coronavirus disease (COVID-19) pandemic, many countries have implemented various mitigation measures to contain the spread of the disease. By engaging with health service providers, the community's participation in adherence to preventive measures is certainly required in the implementation of COVID-19 mitigation strategies. Therefore, this study aimed to assess the level of adherence to COVID-19 preventive measures and its associated factors among the residents, Yangon Region, Myanmar. METHODS: A community-based cross-sectional study was carried out among 636 residents in Yangon Region, Myanmar, from October to December 2021. A multistage non-probability sampling method, purposively selected for three townships in Yangon Region and convenience sampling for 212 participants from each township, was applied and the data were collected by face-to-face interviews using structured and pretested questionnaires. Data were entered, coded, and analyzed using IBM SPSS version 25.0. Simple and multiple logistic regression analysis were performed to identify the significant variables of adherence to COVID-19 preventive measures. RESULTS: As a level of adherence to COVID-19 preventive measures, the proportion of residents who had good adherence was 39.3% (95% CI 35.5-43.2%), moderate adherence was 37.6% (95% CI 33.8-41.5%), and poor adherence was 23.1% (95% CI 19.9-26.6%). The age group of 31-40 years (AOR: 3.13, 95% CI 1.62-6.05), 30 years and younger (AOR: 3.22, 95% CI 1.75-5.92), Burmese ethnicity (AOR: 2.52, 95% CI 1.44-4.39), own business (AOR: 3.19, 95% CI 1.15-8.87), high school education level and below (AOR: 1.64, 95% CI 1.02-2.69), less than 280.90 USD of monthly family income (AOR: 1.51, 95% CI 1.01-2.29), low knowledge about COVID-19 (AOR: 1.90, 95% CI 1.26-2.88) were significantly associated with poor adherence to COVID-19 preventive measures. CONCLUSIONS: In this study, nearly one-fourth of the residents were experiencing poor adherence to COVID-19 preventive measures. Therefore, building up the risk communication through the community using widely used mainstream media, the continuation of disease surveillance and announcement of updated information or advice for the public to increase awareness towards COVID-19, and enforcement to follow the recommended directions and regulations of health institutions are vital to consider for improving the adherence to preventive measures against COVID-19 among the residents.

Clinical Audit of Manipulation of Paediatric Forearm Fractures in the Emergency Department at a District General Hospital: A Quality Improvement Project.

Background Early reduction of paediatric forearm fractures under procedural analgesia has the benefit of avoiding admission and general anaesthesia. In addition to lowering the risks of treatment and reducing the number of treatment episodes, this approach also reduces the psychological stresses on the child and the parents. British Orthopaedic Association Standards for Trauma and Orthopaedics (BOAST) and Getting It Right First Time (GIRFT) guidelines recommend that all units managing paediatric fractures should have protocols to facilitate procedural analgesia for manipulation of forearm fractures. A recent standard operating procedure has been created for this purpose and has outlined local standards to adhere to. Regular audits of paediatric manipulations in the emergency department must be undertaken in line with GIRFT recommendations. The aim is to identify potential barriers to implementation, which can be improved, and to ensure that a high standard of care is delivered.  Aim The aim of this study was to assess the effects of the introduction of local guidelines on the manipulation of paediatric fractures in the emergency department, to assess the adherence of the emergency/orthopaedic departments with these guidelines, and to assess the outcome of all childhood forearm manipulations at University Hospitals Dorset (UHD), to help guide further practice. Material and methods This was a retrospective and prospective study in which the patients admitted to Poole Hospital, Poole, United Kingdom were identified according to the criteria and were analyzed in three separate groups in terms of pre-implementation and post-implementation. Patients were gathered from the orthopaedic on-call trauma lists. All paediatric patients who had a forearm fracture were included (including those who were not manipulated). The first group was the surveillance group in which a clinical audit was completed to review if any of the paediatric patients with forearm fractures were being manipulated in accident and emergency (A&E). The second group included the patients for whom the first standard operating procedure documentation was initiated with the intention of improving the service provided and reduce the number of paediatric forearm fractures going to theatre for simple manipulation and prevent a general anaesthetic. The third group was to review the established pathway and to see which areas of the pathway needed focus to make it better and more in line with the flow of patients through the emergency department. These plan, do, study, act (PDSA) cycles took place from March 2022 to March 2023. Paediatric patients with open or neurovascular damage were excluded from the cohort. The findings and the data were analysed in Microsoft Excel (Microsoft Corporation, Redmond, Washington, United States) and presented through regional meetings to discuss the progress and potential changes in making the pathway by involving all the stakeholders, i.e., the emergency department, orthopaedic department, and theatre managers. Results  An overall reduction was seen in paediatric forearm fractures going to theatre. Almost 30% of the forearm fractures were attended to in the emergency department, identification of factors that affect the numbers was quantified, and improvement in documentation throughout the PDSA cycles was observed.

Transcutaneous bilirubin-based screening reduces the need for blood exchange transfusion in Myanmar newborns: A single-center, retrospective study.

Background: Neonatal hyperbilirubinemia is a significant health problem in Myanmar. We introduced transcutaneous bilirubin (TcB) measurements in 2017 and developed an hour-specific TcB nomogram for early detection and treatment of hyperbilirubinemia in Myanmar neonates. This study aimed to evaluate whether our screening method for hyperbilirubinemia decreased the requirement of blood exchange therapy (ET). Methods: This retrospective cohort study was conducted at the Central Women's Hospital, Yangon. Two groups were included as follows: group 1 (control group; comprising infants born in 2016 and screened on the basis of Kramer's rule), and group 2 (intervention group; comprising infants born in 2019 and screened by TcB measurement using a nomogram). The number of ETs was analyzed based on causes of hyperbilirubinemia and number of days after birth. Results: Groups 1 and 2 comprised 12,968 and 10,090 infants, respectively. Forty-six and two infants in Groups 1 and 2, respectively, required an ET. The odds ratio for ET was 18.0 (Group 1 to Group 2; 95% confidence interval [CI]: 4.8-67.1; p = 0.000). Serum bilirubin values at the time ET was administered were significantly higher in Group 1 than those in Group 2 (median: 23.0 and 16.8, respectively). Conclusion: The management of hyperbilirubinemia using our screening method (TcB Nomogram) can effectively reduce the need for ET in neonates in Myanmar.

Genomic Tracking of SARS-CoV-2 Variants in Myanmar.

In December 2019, the COVID-19 disease started in Wuhan, China. The WHO declared a pandemic on 12 March 2020, and the disease started in Myanmar on 23 March 2020. In December 2020, different variants were brought worldwide, threatening global health. To counter those threats, Myanmar started the COVID-19 variant surveillance program in late 2020. Whole genome sequencing was done six times between January 2021 and March 2022. Among them, 83 samples with a PCR threshold cycle of less than 25 were chosen. Then, we used MiSeq FGx for sequencing and Illumina DRAGEN COVIDSeq pipeline, command line interface, GISAID, and MEGA version 7 for data analysis. In January 2021, no variant was detected. The second run, during the rise of cases in June 2021, showed Alpha, Delta, and Kappa variants. The third and the fourth runs in August and December showed only a Delta variant. Omicron and Delta variants were detected during the fifth run in January 2022. The sixth run in March 2022 showed only Omicron BA.2. Amino acid mutation at the receptor binding domain of Spike glycoprotein started since the second run coupling with high transmission, recurrence, and vaccine escape. We also found the mutation at the primer targets used in current RT-PCR platforms, but there was no mutation at the existing antiviral drug targets. The occurrence of multiple variants and mutations claimed vigilance at ports of entry and preparedness for effective control measures. Genomic surveillance with the observation of evolutionary data is required to predict imminent threats of the current disease and diagnose emerging infectious diseases.

Assessment of depressive symptoms in patients with COVID-19 during the second wave of epidemic in Myanmar: A cross-sectional single-center study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) pandemic has had a great impact on every aspect of society. All countries launched preventive measures such as quarantine, lockdown, and physical distancing to control the disease spread. These restrictions might effect on daily life and mental health. This study aimed to assess the prevalence and associated factors of depressive symptoms in patients with COVID-19 at the Treatment Center. METHODS: A cross-sectional telephone survey was carried out at Hmawbi COVID-19 Treatment Center, Myanmar from December 2020 to January 2021. A total of 142 patients with COVID-19 who met the criteria were invited to participate in the study. A pre-tested Center for Epidemiologic Studies Depression Scale (CES-D) was used as a tool for depressive symptoms assessment. Data were analyzed by using binary logistic regression to identify associated factors of depressive symptoms. Adjusted odds ratio (AOR) with a 95% confidence interval (CI) was computed to determine the level of significance with a p < 0.05. RESULTS: The prevalence of depressive symptoms in patients with COVID-19 was 38.7%, with the means (± standard deviation, SD) subscale of somatic symptom, negative effect, and anhedonia were 4.64 (±2.53), 2.51 (± 2.12), and 5.01 (± 3.26), respectively. The patients with 40 years and older (AOR: 2.99, 95% CI: 1.36-6.59), < 4 of household size (AOR: 3.45, 95% CI: 1.46-8.15), ≤ 400,000 kyats of monthly family income (AOR: 2.38, 95% CI: 1.02-5.54) and infection to family members (AOR: 4.18, 95% CI: 1.74-10.07) were significant associated factors of depressive symptoms. CONCLUSION: The high prevalence of depressive symptoms, approximately 40%, was found in patients with COVID-19 in the Treatment Center. Establishments of psychosocial supports, providing psychoeducation, enhancing the social contact with family and friends, and using credible source of information related COVID-19 would be integral parts of mental health services in COVID-19 pandemic situation.

Nitric oxide acts as an antioxidant and inhibits programmed cell death induced by aluminum in the root tips of peanut (Arachis hypogaea L.).

Aluminum (Al) causes programmed cell death (PCD) in plants. Our previous studies have confirmed that nitric oxide (NO) inhibits Al-induced PCD in the root tips of peanut. However, the mechanism by which NO inhibits Al-induced PCD is unclear. Here the effects of NO on mitochondrial reactive oxygen species (ROS), malondialdehyde (MDA), activities of superoxide dismutase (SOD) and ascorbate peroxidase (APX), expression of alternative oxidase (AhAOX) and cytochrome oxidase (AhCOX) were investigated in peanut (Arachis hypogaea L.) root tips treated with Al. The results showed that Al stress induced rapid accumulation of H2O2 and MDA and increased the ratio of SOD/APX. The up-regulation of AhAOX and AhCOX expressions was not enough to inhibit PCD occurrence. Sodium nitroprusside (SNP, a NO donor) decreased the ratio of SOD/APX and eliminated excess H2O2 and MDA, thereby inhibiting Al-induced PCD in the root tips of peanut. The expression of AhAOX and AhCOX was significantly enhanced in Al-induced PCD treated with SNP. But cPTIO (a NO specific scavenger) supply had the opposite effect. Taken together, these results suggested that lipid peroxidation induced by higher levels of H2O2 was an important cause of Al-induced PCD. NO-mediated inhibition of Al-induced PCD was related to a significant elimination of H2O2 accumulation by decreasing the ratio of SOD/APX and up-regulating the expression of AhAOX and AhCOX.

Two Year Outcomes, Cognitive and Behavioral Markers of Decline in Healthy, Cognitively Normal Older Persons with Global Deterioration Scale Stage 2 (Subjective Cognitive Decline with Impairment).

BACKGROUND: Little is known with respect to behavioral markers of subjective cognitive decline (SCD), a condition initially described in association with Global Deterioration Scale (GDS) stage 2. OBJECTIVE: Two-year interval behavioral markers were investigated herein. METHODS: Subjects from a published 7-year outcome study of GDS stage 2 subjects were selected. This study had demonstrated a hazard ratio of 4.5 for progression of GDS stage 2, in comparison with GDS stage 1 (no subjective or objective cognitive decline) subjects, after controlling for demographic and temporal variables. Because GDS 2 subjects have previously demonstrated impairment in comparison with healthy persons free of complaints, we herein suggest the terminology "SCD(I)" for these persons. 98 SCD(I) persons, 63 women and 35 men, mean baseline age, 67.12±8.75 years, with a mean educational background of 15.55±2.60 years, and mean baseline MMSE scores of 28.9±1.24 were followed for 2.13±0.30 years. RESULTS: Observed annual decline on the GDS was 6.701% per annum, very close to a 1986 published estimate. At follow up, the MMSE, and 7 of 8 psychometric tests did not decline significantly. Of 21 Hamilton Depression Scale items, 2 improved and the remainder were unchanged. Anxieties declined from multiple perspectives. The Brief Cognitive Rating Scale (BCRS) declined significantly (p < 0.001), with component declines in Remote memory (p < 0.01), and Functioning/self-care (p = 0.01). CONCLUSION: SCD(I) persons decline at an annual rate of approximately 6.7% /year from several recent studies. The BCRS assessments and the Digit Symbol Substitution Test can be sensitive measures for future studies of progression mitigation.

Analysis of Mitochondrial Markers of Programmed Cell Death.

Mitochondria play a crucial role in programmed cell death (PCD) in plants. In most cases of mitochondria-dependent PCD, cytochrome c (Cyt c) released from mitochondria due to the opening of mitochondrial permeability transition pore (MPTP) and the activation of caspase-like proteases. Here we describe the analytic methods of mitochondrial markers of PCD including mitochondria isolation, mitochondrial membrane permeability, mitochondrial inner membrane potential, Cytc release, ATP, and mitochondrial reactive oxygen species (ROS).

Microscopic investigation of the memory effect found in micropatterned nematic liquid crystal cells.

Isotropic untreated indium-tin-oxide layers can cause memory alignment of nematic liquid crystals. We have demonstrated an experimental method to characterize this effect by using a micropatterned surface. We tried to imprint a high tilt on an indium-tin-oxide substrate surface. We also investigated microscopic switching behavior of a memory-induced nematic liquid crystal cell by means of a vertical field effect.

Nitric oxide inhibits aluminum-induced programmed cell death in peanut (Arachis hypoganea L.) root tips.

It had been reported that Aluminum (Al) stress altered nitric oxide (NO) concentration and induced programmed cell death (PCD) in plants. However, the relationship between NO and PCD occurrence under Al stress is unclear. The results showed that cell death induced by Al was significant negative correlation with the inhibition of Al on root elongation growth in peanut. AlCl3 at 100µmolL-1 induced DNA ladder, chromatin condensation, typical apoptotic chromatin condensation staining with DAPI, apoptosis related gene Hrs203j expression and caspase3-like protease activation in peanut root tip cells, and showed that Al-induced cell death in peanut root tip cells was a typical PCD. Exogenous NO donor sodium nitroprusside (SNP) at 200µmolL-1 inhibited Al-induced PCD occurrence, but NO specific scavenger cPTIO aggravated PCD production. It suggests that NO is a negative regulator of Al-induced PCD in peanut root tips.

Aluminum induces rapidly mitochondria-dependent programmed cell death in Al-sensitive peanut root tips.

BACKGROUND: Although many studies suggested that aluminum (Al) induced programmed cell death (PCD) in plants, the mechanism of Al-induced PCD and its effects in Al tolerance is limited. This study was to investigate the mechanism and type of Al induced PCD and the relationship between PCD and Al tolerance. RESULTS: In this study, two genotypes of peanut 99-1507 (Al tolerant) and ZH2 (Al sensitive) were used to investigate Al-induced PCD. Peanut root growth inhibition induced by AlCl3 was concentration and time-dependent in two peanut varieties. AlCl3 at 100 µM could induce rapidly peanut root tip PCD involved in DNA cleavage, typical apoptotic chromatin condensation staining with DAPI, apoptosis related gene Hrs203j expression and cytochrome C (Cyt c) release from mitochondria to cytosol. Caspase3-like protease was activated by Al; it was higher in ZH2 than in 99-1507. Al increased the opening of mitochondrial permeability transition pore (MPTP), decreased inner membrane potential (ΔΨm) of mitochondria. Compared with the control, Al stress increased O2•- and H2O2 production in mitochondria. Reactive oxygen species (ROS) burst was produced at Al treatment for 4 h. CONCLUSIONS: Al-induced PCD is earlier and faster in Al-sensitive peanut cultivar than in Al-tolerant cultivar. There is a negative relationship between PCD and Al resistance. Mitochondria- dependence PCD was induced by Al and ROS was involved in this process. The mechanism can be explained by the model of acceleration of senescence under Al stress.

Staging: relevance for trial design in vascular burden of the brain.

Cerebrovascular small vessel disease is now believed to be the major source of vascular burden of the brain. Cerebrovascular small vessel disease and Alzheimer's disease appear to represent pathophysiologic and clinical continua, rather than dichotomous entities. It appears that common etiopathologic mechanisms underlie the clinical presentation of both of these conditions. Therefore, the staging procedures that have been developed for the clinical continuum of age-associated memory impairment, mild cognitive impairment, and the progressive dementia of Alzheimer's disease appear to be applicable for the same continua in cerebrovascular small vessel disease. Although temporal and prognostic aspects have been studied for the Alzheimer's-related portions of this clinical staging continuum, they remain to be elucidated for cerebrovascular small vessel disease.