High-risk and silent clonal hematopoietic genotypes in patients with nonhematologic cancer.

ABSTRACT: Clonal hematopoiesis (CH) identified by somatic gene variants with variant allele fraction (VAF) ≥ 2% is associated with an increased risk of hematologic malignancy. However, CH defined by a broader set of genotypes and lower VAFs is ubiquitous in older individuals. To improve our understanding of the relationship between CH genotype and risk of hematologic malignancy, we analyzed data from 42 714 patients who underwent blood sequencing as a normal comparator for nonhematologic tumor testing using a large cancer-related gene panel. We cataloged hematologic malignancies in this cohort using natural language processing and manual curation of medical records. We found that some CH genotypes including JAK2, RUNX1, and XPO1 variants were associated with high hematologic malignancy risk. Chronic disease was predicted better than acute disease suggesting the influence of length bias. To better understand the implications of hematopoietic clonality independent of mutational function, we evaluated a set of silent synonymous and noncoding mutations. We found that silent CH, particularly when multiple variants were present or VAF was high, was associated with increased risk of hematologic malignancy. We tracked expansion of CH mutations in 26 hematologic malignancies sequenced with the same platform. JAK2 and TP53 VAF consistently expanded at disease onset, whereas DNMT3A and silent CH VAFs mostly decreased. These data inform the clinical and biological interpretation of CH in the context of nonhematologic cancer.

The Impact of Routine Vaccinations on Alzheimer's Disease Risk in Persons 65 Years and Older: A Claims-Based Cohort Study using Propensity Score Matching.

BACKGROUND: Accumulating evidence suggests that adult vaccinations can reduce the risk of developing Alzheimer's disease (AD) and Alzheimer's disease related dementias. OBJECTIVE: To compare the risk for developing AD between adults with and without prior vaccination against tetanus and diphtheria, with or without pertussis (Tdap/Td); herpes zoster (HZ); or pneumococcus. METHODS: A retrospective cohort study was performed using Optum's de-identified Clinformatics® Data Mart Database. Included patients were free of dementia during a 2-year look-back period and were≥65 years old by the start of the 8-year follow-up period. We compared two similar cohorts identified using propensity score matching (PSM), one vaccinated and another unvaccinated, with Tdap/Td, HZ, or pneumococcal vaccines. We calculated the relative risk (RR) and absolute risk reduction (ARR) for developing AD. RESULTS: For the Tdap/Td vaccine, 7.2% (n = 8,370) of vaccinated patients and 10.2% (n = 11,857) of unvaccinated patients developed AD during follow-up; the RR was 0.70 (95% CI, 0.68-0.72) and ARR was 0.03 (95% CI, 0.02-0.03). For the HZ vaccine, 8.1% (n = 16,106) of vaccinated patients and 10.7% (n = 21,417) of unvaccinated patients developed AD during follow-up; the RR was 0.75 (95% CI, 0.73-0.76) and ARR was 0.02 (95% CI, 0.02-0.02). For the pneumococcal vaccine, 7.92% (n = 20,583) of vaccinated patients and 10.9% (n = 28,558) of unvaccinated patients developed AD during follow-up; the RR was 0.73 (95% CI, 0.71-0.74) and ARR was 0.02 (95% CI, 0.02-0.03). CONCLUSION: Several vaccinations, including Tdap/Td, HZ, and pneumococcal, are associated with a reduced risk for developing AD.

The mediating role of work-family conflicts in the association between work ability and depression among Egyptian civil workers.

BACKGROUND: Work ability and work-family conflicts (total-WFCs) were associated with the risk of depression among the working population. METHODS: We recruited 3104 Egyptian civil workers between October 2019 and January 2020. The Work Ability Index (WAI), Center for Epidemiologic Studies-Depression (CES-D) and Midlife Development in the United States questionnaires were used to collect the data. Following Baron and Kenny criteria, the mediation effect of total-WFCs on the association between WAI and CES-D scores was tested by multivariable linear regression models. RESULTS: Findings revealed a high prevalence of depressive symptoms (CES-D score ≥ 16) among Egyptian civil servants (43.4%). There were negative relationships between WAI score and both CES-D score (B = -0.70, P < 0.001) and total-WFCs score (B = -0.22, P < 0.001). Moreover, WAI score was still significantly associated with CES-D score after controlling for total-WFCs score (B = -0.40, P < 0.001) that suggests partial mediation. We estimated that ~44%, 38% and 20% of the total effect of work ability on the risk of depressive symptoms were mediated by total-WFCs, family-to-work conflict and work-to-family conflict, respectively. CONCLUSIONS: Interventions aiming for mitigation total-WFCs can help improve employees' mental health and reduce the risk of impaired work ability-related depression.

Distance learning in physiotherapy education during the COVID-19 pandemic: students' satisfaction, perceived quality, and potential predictors of satisfaction.

BACKGROUND AND PURPOSE: Physiotherapy (PT) is an allied health profession that is generally taught at universities with face-to-face learning to deliver the required knowledge and practical skills of PT. The education sector has transitioned to distance learning (DL) during the COVID-19 pandemic. The study aimed to evaluate PT students' perception of quality of DL and satisfaction with DL, and identify potential predictors of student satisfaction with DL during the COVID-19 pandemic. METHODS: A cross-sectional design was used. An online survey included demographic information, and the Distance Education Learning Environments Survey (DELES) was sent to PT students in Jordan. Regression analyses were used to identify the predictors of student satisfaction with DL. RESULTS: A total of 296 students completed the survey. Most students rated the overall quality of DL as good. However, they were not satisfied with DL. Instructor support for students, personal relevance, previous experience in DL, and being a master's student were the potential predictors of DL satisfaction. CONCLUSION: PT students rated the quality of DL as good with low level of satisfaction. Students' perceptions of and satisfaction with using DL were correlated to several potential predictors that could be considered for improving the DL experience in PT education.

To study the association between various levels of cord serum albumin (CSA) and significant neonatal hyperbilirubinemia requiring interventions like phototherapy or exchange transfusion.

Introduction: Hyperbilirubinemia is most common normal physiological phenomenon in neonates affecting almost one third of newborn.it may lead to neuro disability leading to deafness and cerebral palsy which can be prevented if detected and treated as soon as possible. Albumin is produced in seventh week of intrauterine life and it can be measured by cord blood and in this study we can establish serum albumin with neonatal hyperbilirubinemia and can be treated by phototherapy or exchange transfusion. Material and Method: The study consists of 55 randomly selected eligible term neonates delivered at Rajendra Institute of Medical sciences from March 2019 to August 2020. Conclusion: In this study, in term neonates, level of serum albumin in umbilical cord less than 2.8 g/dl has no correlation with occurrence significant hyperbilirubinemia, so a level <2.8 gm/dl of serum albumin in umbilical cord blood can be used as critical value indicator in triaging predict the risk of occurring of significant hyperbilirubinemia in term neonates.level >3.4 gm/dl is considered safe in neonates who are the candidates for early discharge in the absence of other risk factors.

Risk of Alzheimer's Disease Following Influenza Vaccination: A Claims-Based Cohort Study Using Propensity Score Matching.

BACKGROUND: Prior studies have found a reduced risk of dementia of any etiology following influenza vaccination in selected populations, including veterans and patients with serious chronic health conditions. However, the effect of influenza vaccination on Alzheimer's disease (AD) risk in a general cohort of older US adults has not been characterized. OBJECTIVE: To compare the risk of incident AD between patients with and without prior influenza vaccination in a large US claims database. METHODS: Deidentified claims data spanning September 1, 2009 through August 31, 2019 were used. Eligible patients were free of dementia during the 6-year look-back period and≥65 years old by the start of follow-up. Propensity-score matching (PSM) was used to create flu-vaccinated and flu-unvaccinated cohorts with similar baseline demographics, medication usage, and comorbidities. Relative risk (RR) and absolute risk reduction (ARR) were estimated to assess the effect of influenza vaccination on AD risk during the 4-year follow-up. RESULTS: From the unmatched sample of eligible patients (n = 2,356,479), PSM produced a sample of 935,887 flu-vaccinated-unvaccinated matched pairs. The matched sample was 73.7 (SD, 8.7) years of age and 56.9% female, with median follow-up of 46 (IQR, 29-48) months; 5.1% (n = 47,889) of the flu-vaccinated patients and 8.5% (n = 79,630) of the flu-unvaccinated patients developed AD during follow-up. The RR was 0.60 (95% CI, 0.59-0.61) and ARR was 0.034 (95% CI, 0.033-0.035), corresponding to a number needed to treat of 29.4. CONCLUSION: This study demonstrates that influenza vaccination is associated with reduced AD risk in a nationwide sample of US adults aged 65 and older.

An Observational Study on Clinical and Epidemiological Profile of Pediatric Patients with Coronavirus Disease 2019 (COVID-19) Presenting With Comorbidities at RIMS, Ranchi.

Introduction: SARS COVID-19 infection leads to wide range of symptoms in comorbid pediatric patient. In view of its susceptibility affecting pediatric age groups with comorbidities and its potential to increase the mortality rate, it may have adverse effects on the outcome of such children. This study aims at better understanding of clinical profile and its outcome of pediatric population. Method: A total of 50 pediatric patients aged 1 to 17 years with comorbidities and laboratory confirmed COVID-19 that were admitted at the RIMS, Ranchi from 1st April 2020 to 31st December 2020 were studied. Result: 34 (68%) resided in the hot spot areas of the region, 8(16%) resided in the non- hot spot areas and 8(16%) had migrated from elsewhere. Higher proportion of males between 11-15 years of age were affected (64%).Our study shows that the majority of the children that were affected were of the age group 11-15 years (52%). 38(76%) of these children presented with fever as their major complaints, cough in 28(56%), sore throat in 2 (4%), diarrhea in 6(12%), vomiting in 11 (22%), breathing difficulty in 20 (50%) and 30 (60%) had other symptoms. Out of 50 patients admitted, 3 died. In our study majority of comorbid condition was thalassemia major. Conclusion: The presenting characteristics, comorbidities, and severity of illness of pediatric patients with COVID-19 were different, and milder, compared with adults.

To assess the magnitude of autism spectrum disorder in Jharkhand by M-CHAT-R as a screening tool.

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder which is a clinically heterogenous condition with a wide range of etiological factors and causing significant public health burden. If diagnosed at an earlier age, early interventions can be started this leads to functional outcome of children with ASD with respect to social, behavior and occupational sphere. Therefore, early detection and intervention are widely recommended in these children. So screening of toddlers who were identified to be "at risk" can be diagnosed using screening questionnaires by interviewing parents. Overall with this study we can conclude that, toddlers identified to be "at risk" and those diagnosed with ASD were not uncommon and M-CHAT-R is a useful screening test for the identification of "at risk" toddlers for Autism Spectrum Disorder in Jharkhand.

Steroids from Diplazium esculentum: Antiplasmodial activity and molecular docking studies to investigate their binding modes.

Diplazium esculentum is an edible fern commonly consumed by the local community in Malaysia either as food or medicine. Isolation work on the ethyl acetate extract of the stem of D. esculentum resulted in the purification of two steroids, subsequently identified as stigmasterol (compound 1) and ergosterol5,8-endoperoxide (compound 2). Upon further testing, compound 2 displayed strong inhibitory activity against the Plasmodium falciparum 3D7 (chloroquine-sensitive) strain, with an IC50 of 4.27±1.15 µM, while compound 1 was inactive. In silico data revealed that compound 2 showed good binding affinity to P. falciparum-Sarco endoplasmic reticulum calcium-dependent ATPase (PfATP6); however, compound 1 did not show an antiplasmodial effect due to the lack of a peroxide moiety in the chemical structure. Our data suggested that the antiplasmodial activity of compound 2 from D. esculentum might be due to the inhibition of PfATP6, which resulted in both in vitro and in silico inhibitory properties.

Steroids from Diplazium esculentum: Antiplasmodial activity and molecular docking studies to investigate their binding modes

@#Diplazium esculentum is an edible fern commonly consumed by the local community in Malaysia either as food or medicine. Isolation work on the ethyl acetate extract of the stem of D. esculentum resulted in the purification of two steroids, subsequently identified as stigmasterol (compound 1) and ergosterol5,8-endoperoxide (compound 2). Upon further testing, compound 2 displayed strong inhibitory activity against the Plasmodium falciparum 3D7 (chloroquine-sensitive) strain, with an IC50 of 4.27±1.15 µM, while compound 1 was inactive. In silico data revealed that compound 2 showed good binding affinity to P. falciparum-Sarco endoplasmic reticulum calcium-dependent ATPase (PfATP6); however, compound 1 did not show an antiplasmodial effect due to the lack of a peroxide moiety in the chemical structure. Our data suggested that the antiplasmodial activity of compound 2 from D. esculentum might be due to the inhibition of PfATP6, which resulted in both in vitro and in silico inhibitory properties.

Neonatal sacrococcygeal teratoma: Our 20-year experience from a tertiary care centre in North India.

Advances in diagnostic and therapeutic interventions have improved the survival of neonates with sacrococcygeal teratoma in richer countries. These changes have not yet taken place in resource-limited settings. A retrospective analysis of neonates with sacrococcygeal teratoma operated at our centre during 1997-2016 was performed. Among 44 neonates enrolled, prenatal diagnosis of sacrococcygeal teratoma was available in 25% of pregnancies. All babies except one were born vaginally. Associated congenital malformations were seen in 20% (9/44). Types of sacrococcygeal teratoma were classified as Altman type I in 12 (27.3%), 24 (54.5%) as type II, 6 (13.6%) as type III and 2 (4.5%) as type IV. Morphologically, 77% (34/44) neonates had cystic lesions. All patients were managed successfully by total excision. Histopathology confirmed mature teratoma in 43 (97.7%). After a 12-month follow-up, no recurrence was observed. An uneventful pregnancy, absence of associated congenital anomalies, cystic morphology and a mature histology are good prognostic factors.

Efficacy and Safety of Tocilizumab for Polyarticular-Course Juvenile Idiopathic Arthritis in the Open-Label Two-Year Extension of a Phase III Trial.

OBJECTIVE: To report the 2-year efficacy and safety of tocilizumab (TCZ) in patients with polyarticular-course juvenile idiopathic arthritis (JIA). METHODS: Patients ages 2-17 years with active polyarticular-course JIA, in whom treatment with methotrexate was unsuccessful, received 16 weeks of open-label intravenous TCZ in part 1 (once every 4 weeks: 8 mg/kg or 10 mg/kg for body weight [BW] <30 kg; 8 mg/kg for BW ≥30 kg). Assessments were based on the JIA-American College of Rheumatology (ACR) response (defined as percentage of improvement in ≥3 of the 6 JIA core response variables [CRVs]). Patients with at least a JIA-ACR30 response (defined as ≥30% improvement in ≥3 of the 6 JIA CRVs without worsening in >1 of the remaining JIA CRVs by >30%) at week 16 were randomly assigned (1:1) to receive TCZ or placebo in part 2. Patients remained in part 2 until either week 40 or the occurrence of JIA flare. Upon starting part 3, all patients received open-label TCZ. At week 104 of the study, efficacy was assessed using JIA-ACR50/70/90 response rates (defined as 50%, 70%, or 90% improvement, respectively), achievement of inactive disease, and the Juvenile Arthritis Disease Activity Score in 71 joints (JADAS-71). Safety was assessed in the all-exposure population per 100 patient-years of exposure. RESULTS: Overall, 188 patients entered part 1, 166 patients entered part 2, and 160 patients entered part 3. By week 104, among the 188 patients in the modified intent-to-treat group who received TCZ, JIA-ACR50/70/90 response rates were 80.3%/77.1%/59.6%, respectively, the median JADAS-71 score decreased from 3.6 at week 40 to 0.7 at week 104, 51.1% of patients had achieved inactive disease, and 31 of 66 patients who had been receiving glucocorticoids discontinued them. Adverse event (AE) and serious AE rates were 406.5 per 100 patient-years and 11.1 per 100 patient-years, respectively. The infection rate was 151.4 per 100 patient-years, and the serious infection rate was 5.2 per 100 patient-years. CONCLUSION: Patients treated with TCZ for polyarticular-course JIA showed high-level disease control for up to 2 years. The TCZ safety profile was consistent with that previously reported.

Role of 18f-fdg-pet/ct in assessment of pediatric Hodgkin's lymphoma.

AIM: To assess the prognostic role of interim 18FFDGPET/CT in pediatric patients with Hodgkin's lymphoma (PHL). METHODS: Prospective analysis of 254 Saudi patients with pathologically proven PHL, they underwent interim 18F-FDG-PET/CT after 2 cycles of ABVD with baseline study, analysis of interim 18F-FDG-PET/CT was done visually according to the Deauville score (5-point score) as well as semi-quantitative analysis using maximum standardized uptake value (SUVmax), average SUV (SUVmean2.5 and SUVmean40). The parameters were calculated as absolute values and as percentages of difference between the initial and the interim hottest residual lesion. Follow-up was done for period of 2.9 years (range, 0.9 to 5.2 years). clinical outcomes were obtained from medical records. RESULTS: two hundred and twenty out of 254 children showed PET-ve interim while 34 were still PET+ve. Univariate analysis showed that the risk stratification, qualitative analysis of interim 18F-FDG-PET/CT were significant predictors for total actuarial survival (TAS) and disease free survival (DFS). Among the semiquantitative parameters, ΔSUVmean2.5 has the highest hazard ratio. In multivariate analysis, the current study revealed that the three above factors were important prognostic factors that can predict TAS and DFS. However, visual assessment of interim PET canceled the prognostic impact of ΔSUVmean2.5. CONCLUSIONS: visual assessment of early interim 18F-FDG-PET/CT after 2 cycles of ABVD in PHL showed a very significant role in prediction ofTAS and DFS.

Influence of Lithium Vacancy Defects on Tritium Diffusion in ß-Li2TiO3.

Lithium metatitanate, Li2TiO3, is a leading candidate for application as a tritium breeding material in a future fusion reactor. Following transmutation of lithium, the tritium must escape the crystal in order to be extracted for use in the fusion plasma. The rate-limiting step to release tritium from the Li2TiO3 pebbles is diffusion through the crystal grains. In this work, the activation barriers for tritium diffusion have been calculated using density functional theory. The results show that tritium can diffuse as an interstitial with a barrier of 0.52 eV. However, when a tritium ion becomes bound to a lithium vacancy defect, the energy required to either detrap the tritium from the vacancy or for the cluster to diffuse increases to >1 eV. Overall, these results suggest that the introduction of lithium vacancies due to Li burn-up may lead to an increase in tritium retention in the pebbles.

Betta nuluhon, a new species of fighting fish from western Sabah, Malaysia (Teleostei: Osphronemidae).

Betta nuluhon, new species, is described from a hill stream habitat in western Sabah. This species is allied to both B. chini and B. balunga, and differs from rest of its congeners in the B. akarensis group in having the following combination of characters: yellow iris when live; mature males with greenish-blue iridescence on opercle when live; mature fish with distinct transverse bars on caudal fin; slender body (body depth 22.1-25.2 % SL); belly area with faint reticulate pattern (scales posteriorly rimmed with black); absence of tiny black spots on anal fin; lateral scales 29-31 (mode 30); predorsal scales 20-21 (mode 20). Notes on a fresh series of B. chini are also provided.

Dielectric properties and in vitro hemocompatibility of Nd:YAG laser-irradiated polyethylene terephthalate.

Surface properties and morphology of the biomaterial play an essential role in the polymer-material interaction. In this work, laser surface modification of polyethylene terephthalate as a polymer with distinguished mechanical properties was carried out using (neodymium-doped yttrium aluminum garnet) Nd:YAG laser (1.064 µm) with different output power (0.3, 3, and 6 W). The structural, surface, and dielectric properties of PET before and after laser irradiation have been studied using attenuation total reflection-Fourier transform infrared (ATR-FTIR), dielectric spectroscopy (DS), scanning electron microscope (SEM), and contact angle measurements. Moreover, the anticoagulant properties of the laser-irradiated PET was determined through measuring the prothrombin time (PT), partial thromboplastin time (PTT), and international normalized ratio (INR). In vitro platelet adhesion test was used to assess the platelets adhered to the surface of the samples; in addition to hematological study. It was found that contact angle (θ) measurements of laser-irradiated PET samples decreased compared to the unirradiated PET. The irradiated samples at 0.3 W have the lowest contact angle which is a clear indication that surface treatment with Nd:YAG laser brought about improving the wettability of the polymer. From the dielectric measurements, both values of permittivity and dielectric loss decrease by increasing the laser power. The electrical conductivity decreases with increasing laser power, but still in the same order 10-14 S/cm. The decrease in electrical conductivity σ may be due to the cross-linking of the polymeric matrix which led to a decrease in the total polarity and consequently decrease in electrical conductivity. The magnitude of σ obtained is highly recommended to be used for insulator purposes in addition to the main purpose that is blood contact.

Preparation and characterization of polyethylene terephthalate-chamomile oil blends with enhanced hydrophilicity and anticoagulant properties.

New blend films based on polyethylene terephthalate (PET) with different concentrations (50, 100 and 200 µL) of chamomile oil (CAO) were prepared. The effect of oil on the dielectric properties, structural and surface properties of PET was studied. The wettability of the blend films was evaluated by contact angle measurements. In vitro platelet adhesion on the surface and coagulation assessment were conducted to evaluate the behavior of the new blends for blood contact applications. Results of the study indicate that the wettability of PET-CAO blends up to 100 µL has been enhanced relative to the pure PET as indicated by the decrease in contact angle measurements. The attenuation total reflection-Fourier transform infrared spectra of the blends confirmed the presence of chamomile oil in the polymer matrix and suggested the presence of interaction between them. The permittivity ε' values decreased by increasing oil content upto 100 µL. On the other hand, the values of dielectric loss ε″ were found to increase by increasing oil content to 100 µL after which it decreased. The delay in partial thromboplastin time (PTT) of the blood would validate the anti-coagulant property of PET-CAO blends. The results demonstrated that the PET-CAO blends with concentration of 100 µL could be considered as a promising candidate material in blood contact application.

Medico-legal autopsies of homicidal deaths: A five-year retrospective study in Hospital Sungai Buloh.

INTRODUCTION: Homicide is the act of killing one human being by another, encompassing death as a result of criminal act including justifiable homicide such as judicial killing and self-defence. This study aimed to ascertain the epidemiology and patterns of injury of homicide victims. MATERIALS AND METHODS: We reviewed records of medico-legal autopsy cases performed at the Department of Forensic Medicine, Hospital Sungai Buloh, for a period of five years, from January 2012 until December 2016. Subjects' demographic data such as age, gender, nationality, ethnicity and cause of death were recorded. RESULTS: A total of 122 homicide cases were documented. 90% of the victims were 18 to 65 years old. Males contributed 80% of the subjects. An alarming 42% of the subjects comprised of non-Malaysians. Indonesian subjects contributed one-third of the non-citizen category, followed by Bangladeshis at 20.4%. Other nationalities were Burmese, Nepalese, Pakistani, Vietnamese and unspecified. Among Malaysians, 50% of the subjects were Indians, followed by Malay (31.5%) and Chinese (17.8%). Sharp and blunt force traumas were the most common injuries found, contributing 33% and 32% respectively. Asphyxiation and firearm injuries recorded an almost similar frequency, contributing 25% in combination. Other patterns included combined sharp and blunt objects (4.9%) and burns (3%). CONCLUSIONS: A large number of immigrants in the country have significantly increased the forensic casework. Sharp and blunt objects continue to be the weapon of choice due to its easy accessibility. As domestic violence including fatal spousal and child abuse continue to rise, in-depth study in the area is warranted.