Bilateral vision loss at high altitude: A diagnostic dilemma.

A young male patient of 22 years inducted at 11,000 feet altitude presented with a sudden onset bilateral diminution of vision associated with easy fatiguability and generalised weakness. Fundus examination revealed preretinal haemorrhages and Roth spots both eyes, owing to which differential diagnosis of high altitude retinopathy (HAR) and haematological disorders was considered. On systemic examination, he had pallor with massive splenomegaly. Haematological investigation revealed high total leucocyte count (TLC) 2.96 lac (normal 4000-11,000/uL) with peripheral blood smear showing increase in basophils, neutrophil precursors, myelocyte bulge, anaemia with no blasts suggestive of chronic myeloid leukaemia-chronic phase. Hence, a diagnosis of chronic myeloid leukaemia (chronic phase) with no features of tumour lysis syndrome was made. Patient was started on Tab hydroxyurea 50 mg twice a daily and managed by haemato-oncologist and required no further active ophthalmological intervention.

Comprehensive analysis of non-synonymous missense SNPs of human galactose mutarotase (GALM) gene: an integrated computational approach.

Missense Non-synonymous single nucleotide polymorphisms (nsSNPs) of Galactose Mutarotase (GALM) are associated with the Novel type of Galactosemia (Galactosemia type 4) together with symptoms such as high blood galactose levels and eye cataracts. The objective of the present study was to identify deleterious nsSNPs of GALM recorded on the dbSNP database through comprehensive insilico analysis. Among the 319 missense nsSNPs reported, various insilco tools predicted R78S, R82G, A163E, P210S, Y281C, E307G and F339C as the most deleterious mutations. Structural analysis, PTM analysis and molecular dynamics simulations (MDS) were carried out to understand the effect of these mutations on the structural and physicochemical properties of the GALM protein. The residues R82G and E307G were found to be part of the binding site that resulted in decreased surface accessibility. Replacing the charged wild-type residue with a neutral mutant type affected its substrate binding. All 7 mutations were found to increase the rigidity of the protein structure, which is unfavorable during ligand binding. The mutation F339E made the protein structure more rigid than all the other mutations. Y281 is a phosphorylated site, and therefore, less significant structural changes were observed when compared to other mutations; however, it may have significant differences in the usual functioning of the protein. In summary, the structural and functional analysis of missense SNPs of GALM is important to reduce the number of potential mutations to be evaluated in vitro to understand the association with some genetic diseases.Communicated by Ramaswamy H. Sarma.

Impact of Perceived Safety and Barriers on Physical Activity Levels in Community-Dwelling Older Adults During the COVID-19 Pandemic in Singapore: A Cross-Sectional Mixed Methods Study.

This descriptive cross-sectional mixed methods study conducted in Singapore aimed to describe community-dwelling older adults' differences in physical activity (PA) based on perceived safety to exercise, barriers to PA, and preferred modes of PA during a pandemic. Out of 268 older adults, 25.4% felt unsafe to exercise during the pandemic. More participants who felt unsafe were aged 75 years and older (72.1% vs. 57.0%, p = .028) and lacked formal education (54.4% vs. 37.0%, p = .040). Barriers included difficulties exercising with masks, family concerns, and exercise center closures. Those who felt unsafe were significantly more likely to exercise at home and had significantly shorter duration of exercise and walks per week (2.72 vs. 4.50 hr, p = .002). Perceived barriers and exercise preferences should be considered when developing programs to improve older adults' PA during pandemics.

Advanced molecular therapies for neurological diseases: focus on stroke, alzheimer's disease, and parkinson's disease.

Neurological diseases (NDs) are one of the leading causes of disability and the second leading cause of death globally. Among these stroke, Alzheimer's disease (AD), and Parkinson's disease (PD) are the most common NDs. A rise in the absolute number of individuals affected with these diseases indicates that the current treatment strategies in management and prevention of these debilitating diseases are not effective sufficiently. Therefore, novel treatment strategies are being explored to cure these diseases by addressing the causative mechanisms at the molecular level. Advanced therapies like gene therapy (gene editing and gene silencing) and stem cell therapies aim to cure diseases by gene editing, gene silencing and tissue regeneration, respectively. Gene editing results in the deletion of the aberrant gene or insertion of the corrected gene which can be executed using the CRISPR/Cas gene editing tool a promising treatment strategy being explored for many other prevalent diseases. Gene silencing using siRNA silences the gene by inhibiting protein translation, thereby silencing its expression. Stem cell therapy aims to regenerate damaged cells or tissues because of their ability to divide into any type of cell in the human body. Among these approaches, gene editing and gene silencing have currently been applied in vitro and to animal models, while stem cell therapy has reached the clinical trial stage for the treatment of NDs. The current status of these strategies suggests a promising outcome in their clinical translation.

Role of tRNA-Derived Fragments in Neurological Disorders: a Review.

tRFs are small tRNA derived fragments that are emerging as novel therapeutic targets and regulatory molecules in the pathophysiology of various neurological disorders. These are derived from precursor or mature tRNA, forming different subtypes that have been reported to be involved in neurological disorders like stroke, Alzheimer's, epilepsy, Parkinson's, MELAS, autism, and Huntington's disorder. tRFs were earlier believed to be random degradation debris of tRNAs. The significant variation in the expression level of tRFs in disease conditions indicates their salient role as key players in regulation of these disorders. Various animal studies are being carried out to decipher their exact role; however, more inputs are required to transform this research knowledge into clinical application. Future investigations also call for high-throughput technologies that could help to bring out the other hidden aspects of these entities. However, studies on tRFs require further research efforts to overcome the challenges posed in quantifying tRFs, their interactions with other molecules, and the exact mechanism of function. In this review, we are abridging the current understanding of tRFs, including their biogenesis, function, relevance in clinical therapies, and potential as diagnostic and prognostic biomarkers of these neurological disorders.

Factors influencing fear of falling in community-dwelling older adults in Singapore: a cross-sectional study.

BACKGROUND: Fear of falling (FoF) has far-reaching implications including activity restriction, functional decline and reduced quality of life. It is a common consequence of falls but may be present even in non-fallers. This study aimed to determine the factors associated with FoF in a segment of Singapore's community-dwelling older adults. METHODS: This descriptive cross-sectional study recruited a convenience sample of adults aged 65 and above from 4 primary care clinics from September 2020 to March 2021. Data were collected on demographic factors, clinical factors such as multi-morbidity, falls characteristics such as history of falls, injuries, and reasons for falls and frailty as determined by the Clinical Frailty Scale (CFS). FoF was measured using the Short Falls Efficacy Scale-International (Short FES-I), cut-off score of 14 and above indicated high FoF. Logistic regression was used to determine factors associated with high FoF. RESULTS: Out of 360 older adults, 78.1% were Chinese and 59.7% females. The mean age was 78.3 years and 76 (21.1%) had a history of falls in the past six months. Almost half (43.1%) were mildly to moderately frail and most (80.6%) had multi-morbidity. The mean FoF score was 15.5 (SD 5.97) and 60.8% reported high FoF. There were statistically significant differences in age, gender, ethnicity, marital status, educational level, use of walking aid, multi-morbidity, frailty status, history of falls within six months and reason for falls between patients who had high FoF versus those who had moderate or low FoF. Logistic regression found that Malay ethnicity (OR = 5.81, 95% CI 1.77-19.13), marital status, use of walking aids (OR = 3.67, 95% CI = 1.54-8.77) and frailty were significant factors associated with high FoF. Compared to those who were never married, the odds of high FoF were significantly higher in married older adults (OR = 6.75, 95% CI 1.39 to 32.76), those who were separated or divorced (OR 10.40, 95% CI 1.13 to 95.76) and those who were widowed (OR = 7.41, 95% CI 1.51 to 36.41). Compared to well older adults, the odds of high FoF were significantly higher in pre frail older adults (OR = 6.87, 95% CI = 2.66-17.37), mildly frail older adults (OR = 18.58, 95% CI = 4.88-70.34) and moderately frail older adults (OR = 144.78, 95% CI = 13.86-1512.60). CONCLUSIONS: The study found that pre frail to moderately frail older adults as determined by CFS have significantly higher risk of high FoF. The demographic factors such as marital status and ethnicity and falls characteristics associated with FoF in this study will be helpful to develop targeted and tailored interventions for FoF.

Which Aspect of Patient-Provider Relationship Affects Acceptance and Adherence of Insulin Therapy in Type 2 Diabetes Mellitus? A Qualitative Study in Primary Care.

PURPOSE: In type 2 diabetes mellitus (T2DM), insulin therapy is often recommended to achieve the optimal control of disease, thereby preventing the onset and progression of diabetes-related complications. Despite knowing about the benefits, it has been reported that 71% of patients refuse insulin and the adherence rate ranges from 30 to 80%. Patient-provider relationship (PPR) may affect such insulin-related behaviours, but little is known about which aspect of PPR affects this. This study aimed to explore the key aspect of the patient-provider relationship that affects the initial insulin acceptance and continued adherence. PATIENTS AND METHODS: We used the grounded theory approach in this qualitative research. The study was conducted at two primary care clinics between September 2019 and January 2021. Patients with T2DM on basal or premixed insulin were recruited using maximum variation sampling. Data were collected using semi-structured in-depth interviews and transcribed verbatim for analysis using constant comparison and synthesis. RESULTS: Twenty-one participants with different levels of diabetes control and adherence were recruited. Four themes that emerged were 1) patient-provider interaction, 2) addressing the psychological fears, 3) gaining confidence in handling insulin equipment and 4) follow-up after insulin initiation. Among the subthemes, trust in doctors, provider's communication skills, patient-centred decision-making and continuity of care positively influenced insulin acceptance and adherence. Conversely, fear of being judged by the provider hindered open communication around non-adherence. Various aspects of interaction with nurses helped in alleviating patient's fear of injection and gaining confidence with the insulin equipment. CONCLUSION: Many aspects of PPR affect insulin acceptance and adherence. Among these, gaining patients' trust, effective patient-provider communication, patient-centred decision-making, and ensuring continuity of care improve both insulin acceptance and treatment adherence. Various interactions with nurses help in addressing fears surrounding injection and gaining acceptance towards insulin therapy. Patients' fear of being blamed or judged by the provider negatively affects open communication around non-adherence.

Impact of patients' beliefs about insulin on acceptance and adherence to insulin therapy: a qualitative study in primary care.

BACKGROUND: Insulin therapy forms a cornerstone of pharmacological management of diabetes mellitus (DM). However, there remains a lack of acceptance and adherence to insulin, thereby contributing to poor DM control. This study aimed to determine the impact of patients' beliefs about insulin on acceptance and adherence to insulin therapy. METHOD: This was a qualitative study using grounded theory approach. The study took place from September 2019 to January 2021 at a cluster of primary healthcare clinics in Singapore. Maximum variation sampling was used to recruit adult patients with type 2 DM on basal or premixed insulin for at least 6 months. Semistructured in-depth interviews were conducted using a topic guide and audio recorded. Data collection continued until saturation. Data analysis utilised a constant comparison procedure and a synthesis approach. RESULTS: Twenty-one participants (mean age 61 years) were interviewed for this study. Data analyses showed that there were 6 main themes that emerged. Four themes influenced both insulin acceptance and adherence. These were concerns about insulin being a lifelong treatment, physical fear of insulin injection, erroneous beliefs about insulin, and perceived fear of DM complications. Two additional themes influenced adherence to insulin therapy. These were socioeconomic concerns, and concerns about side effects of insulin. CONCLUSIONS: Patients' beliefs about insulin impact on the acceptance and adherence to insulin therapy. Health care providers need to elicit and address these beliefs during counselling to improve acceptance and adherence to insulin therapy.

Computational screening of natural compounds from Salvia plebeia R. Br. for inhibition of SARS-CoV-2 main protease.

The novel Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) has emerged to be the reason behind the COVID-19 pandemic. It was discovered in Wuhan, China and then began spreading around the world, impacting the health of millions. Efforts for treatment have been hampered as there are no antiviral drugs that are effective against this virus. In the present study, we have explored the phytochemical constituents of Salvia plebeia R. Br., in terms of its binding affinity by targeting COVID-19 main protease (Mpro) using computational analysis. Molecular docking analysis was performed using PyRx software. The ADMET and drug-likeness properties of the top 10 compounds showing binding affinity greater than or equal to - 8.0 kcal/mol were analysed using pkCSM and DruLiTo, respectively. Based on the docking studies, it was confirmed that Rutin and Plebeiosides B were the most potent inhibitors of the main protease of SARS-CoV-2 with the best binding affinities of - 9.1 kcal/mol and - 8.9 kcal/mol, respectively. Further, the two compounds were analysed by studying their biological activity using the PASS webserver. Molecular dynamics simulation analysis was performed for the selected protein-ligand complexes to confirm their stability at 300 ns. MM-PBSA provided the basis for analyzing the affinity of the phytochemicals towards Mpro by calculating the binding energy, and secondary structure analysis indicated the stability of protease structure when it is bound to Rutin and Plebeiosides B. Altogether, the study identifies Rutin and Plebeiosides B to be potent Mpro inhibitors of SARS-CoV-2. Supplementary Information: The online version contains supplementary material available at 10.1007/s42535-021-00304-z.

Assessment of microsatellite instability for screening bladder cancer in high-risk population.

AIMS: This study aims to determine the diagnostic efficacy of microsatellite markers for screening bladder cancer in population at high risk. MATERIALS AND METHODS: A population of 200 people was screened for bladder cancer using a set of microsatellite markers. Urine samples were obtained from four different types of population groups - Group 1 (healthy population group), Group 2 (current smokers with a smoking history of more than 10 years), Group 3 (bladder cancer group), and Group 4 (bladder cancer group who were former smokers with a history of more than 10 years). Polymerase chain reaction (PCR) was performed to amplify microsatellite sequences at D9S63, D9S156, and D9S283. PCR products were separated on 1.8% agarose gel and were scanned using ultraviolet transilluminator. RESULTS: In Group 2 (high-risk population group, mainly current smokers with a history of more than 10 years), microsatellite alterations were found in 36 out of 50 people. We observed microsatellite alterations in 38 out of 50 people in Group 3 (bladder cancer group) and in 39 out of 50 people in Group 4 (bladder cancer group, mainly former smokers with a history of more than 10 years). The sensitivity of this test in Group 2, Group 3, and Group 4 was found to be 72%, 76% and 78%, respectively. The specificity of this test in each group was found to be 90%. CONCLUSION: Using these set of microsatellite markers, medium sensitivity and high specificity were reported for this test. The current findings suggest that a set of microsatellite markers (D9S63, D9S156, and D9S283) can be used to detect bladder cancer in high-risk population.

Classification, Source, and Effect of Environmental Pollutants and Their Biodegradation.

Any foreign chemical substance that is unusually present within an organism or is unexpectedly found in the environment at a higher concentration than the permissible limits can be termed a xenobiotic or a pollutant. Such substances include carcinogens, drugs, food additives, hydrocarbons, dioxins, polychlorinated biphenyls, pesticides or even some natural compounds. Pollutants are known for their higher persistence and pervasiveness, and along with their transformed products, they can remain in and interact with the environment for prolonged periods. In this article, the classification of such substances based on their nature, use, physical state, pathophysiological effects, and sources is discussed. The effects of pollutants on the environment, their biotransformation in terms of bioaccumulation, and the different types of remediation such as in situ and ex situ remediation, are also presented.

Determination of non-Vitamin K oral anticoagulant (NOAC) effects using a new-generation thrombelastography TEG 6s system.

Non vitamin K oral anticoagulants (NOACs) do not require regular monitoring but information about their pharmacodynamic effect may be importantin situations like trauma, stroke oremergent surgery. Currently, no standardized point-of-care test is available to evaluate the anticoagulant effects of NOACs. We evaluated the anticoagulant effect of NOACs with the next generation point-of-care TEG assay (TEG® 6S) based on a fully-automated thrombelastography system. We used two TEG® 6S assays, the DTI assay and Anti-Factor Xa (AFXa) assay, to detect anticoagulant effects and classify NOACs. Blood from healthy volunteers (n = 26) was used to obtain a baseline reference range. Data derived from patients on factor Xa inhibitors (FXi) (rivaroxaban and apixaban) (n = 39), and direct thrombin inhibitors (DTIs) (dabigatran) (n = 25) were compared against the reference range for detection of drug effect and drug classification. TEG®6s R-time highly correlated to each NOAC. Presence of NOACs caused elongation of R-time on the AFXa assay compared to the reference range (4.3 ± 1.7 vs. 1.3 ± 0.3 min. for FXi, p < 0.001 and 3.5 ± 1.2 vs. 1.3 ± 0.3 min. for DTI, p < 0.001). R-time on the DTI assay was elongated only in presence of a DTI (3.4 ± 1.0 vs. 1.5 ± 0.2 min, p < 0.001). The cutoff for detection of a DTI effect was an R time of 1.9 min and for anti-Xa effect was 1.95 min. For detection of NOAC therapy, there was ≥92% sensitivity and ≥95% specificity. The automated TEG®6s NOAC assay may be an effective tool to identify an anticoagulant effect from NOAC therapy and facilitate care of patients with bleeding or at risk of bleeding in the event of needing emergency surgery.

Role of Bioadsorbents in Reducing Toxic Metals.

Industrialization and urbanization have led to the release of increasing amounts of heavy metals into the environment. Metal ion contamination of drinking water and waste water is a serious ongoing problem especially with high toxic metals such as lead and cadmium and less toxic metals such as copper and zinc. Several biological materials have attracted many researchers and scientists as they offer both cheap and effective removal of heavy metals from waste water. Therefore it is urgent to study and explore all possible sources of agrobased inexpensive adsorbents for their feasibility in the removal of heavy metals. The objective was to study inexpensive adsorbents like various agricultural wastes such as sugarcane bagasse, rice husk, oil palm shell, coconut shell, and coconut husk in eliminating heavy metals from waste water and their utilization possibilities based on our research and literature survey. It also shows the significance of developing and evaluating new potential biosorbents in the near future with higher adsorption capacity and greater reusable options.

Clinicopathologic Features and Outcome of Young Adults With Stage IV Colorectal Cancer.

PURPOSE: Colorectal cancer has a distinct clinicopathologic presentation in younger patients. The aim of this paper was to evaluate the outcome of younger (age below 50 y) and older patients with stage IV (advanced) colorectal cancer in the modern era of combination chemotherapy. METHODS: Cases of metastatic colorectal cancer reported in Surveillance, Epidemiology, and End Results registry (1973 to 2008) were reviewed. Demographics, tumor characteristics, and overall and cancer-specific survivals in patients below 50 and above 50 years of age were compared by Cox proportional hazard analyses. Joinpoint regression analysis was used to evaluate secular trends in 2-year survival. RESULTS: Younger patients had a greater proportion of negative clinicopathologic features (male sex, African American ethnicity, and signet ring or mucinous histology). In multivariate analysis, older age, male sex, African American ethnicity, right-sided tumors, and signet ring histology were associated with higher mortality risk. Younger patients had improved survival (hazard ratio 0.72; 95% confidence interval: 0.70-0.75) compared with older patients, whereas all patients experienced increased 2-year survival by joinpoint analysis beginning in 1999-2000. CONCLUSIONS: The results confirm decreased mortality from advanced colorectal cancer in the era of modern combination chemotherapy in younger and older patients. Younger age, non-right-sided tumors, and absence of signet ring histology significantly associate with better survival.

Reducing depression among community-dwelling older adults using life-story review: a pilot study.

A life-story review can serve as an effective intervention to express one's inner feelings and provide emotional catharsis. The research aim was to examine the effects of life-story review on depression levels in community-dwelling older adults in Singapore. This pilot experimental pre-post-follow-up study was conducted from July 2012 to February 2013. Twenty-nine older Malays aged 60 and above, with mild to moderate depression, were randomly allocated to the life-story review (intervention) group (n = 15) or the non life-story review (control) group (n = 14). Depressive symptoms were measured by the Geriatric Depression Scale-15 and collected five times over eight weeks. Generalized estimating equations were used to examine the effects of the intervention on the elders' depression levels, controlled for age, gender, medication use, existence of chronic disease, and diary writing experience. Reductions in depression scores were found in the intervention group from week 1 (Mean ± SD 5.9 ± 2.3) to week 8 (1.9 ± 1.6) compared with the control group (week 1: 5.0 ± 1.3; week 8: 3.5 ± 1.5). At week 8, the intervention group showed a significantly lower level of depression than the control group (χ(2) = 14.61, p < 0.001). This study adds to prior research supporting the use of life story review in improving depression levels in cognitively intact community dwelling older adults.

Toxicity, mechanism and health effects of some heavy metals.

Heavy metal toxicity has proven to be a major threat and there are several health risks associated with it. The toxic effects of these metals, even though they do not have any biological role, remain present in some or the other form harmful for the human body and its proper functioning. They sometimes act as a pseudo element of the body while at certain times they may even interfere with metabolic processes. Few metals, such as aluminium, can be removed through elimination activities, while some metals get accumulated in the body and food chain, exhibiting a chronic nature. Various public health measures have been undertaken to control, prevent and treat metal toxicity occurring at various levels, such as occupational exposure, accidents and environmental factors. Metal toxicity depends upon the absorbed dose, the route of exposure and duration of exposure, i.e. acute or chronic. This can lead to various disorders and can also result in excessive damage due to oxidative stress induced by free radical formation. This review gives details about some heavy metals and their toxicity mechanisms, along with their health effects.