Publications by authors named "Sonia Singh"

72 Publications

Second Paediatric Strategy Forum for anaplastic lymphoma kinase (ALK) inhibition in paediatric malignancies: ACCELERATE in collaboration with the European Medicines Agency with the participation of the Food and Drug Administration.

Eur J Cancer 2021 Nov 15;157:198-213. Epub 2021 Sep 15.

Hospital for Sick Children, Toronto, Canada.

The first (2017) and sixth (2021) multistakeholder Paediatric Strategy Forums focused on anaplastic lymphoma kinase (ALK) inhibition in paediatric malignancies. ALK is an important oncogene and target in several paediatric tumours (anaplastic large cell lymphoma [ALCL], inflammatory myofibroblastic tumour [IMT], neuroblastoma and hemispheric gliomas in infants and young children) with unmet therapeutic needs. ALK tyrosine kinase inhibitors have been demonstrated to be active both in ALK fusion-kinase positive ALCL and IMT. ALK alterations differ, with fusions occurring in ALCL, IMT and gliomas, and activating mutations and amplification in neuroblastoma. While there are many ALK inhibitors in development, the number of children diagnosed with ALK driven malignancies is very small. The objectives of this ALK Forum were to (i) Describe current knowledge of ALK biology in childhood cancers; (ii) Provide an overview of the development of ALK inhibitors for children; (iii) Identify the unmet needs taking into account planned or current ongoing trials; (iv) Conclude how second/third-generation inhibitors could be evaluated and prioritised; (v) Identify lessons learnt from the experience with ALK inhibitors to accelerate the paediatric development of other anti-cancer targeted agents in the new regulatory environments. There has been progress over the last four years, with more trials of ALK inhibitors opened in paediatrics and more regulatory submissions. In January 2021, the US Food and Drug Administration approved crizotinib for the treatment of paediatric and young adult patients with relapsed or refractory ALCL and there are paediatric investigation plans (PIPs) for brigatinib and for crizotinib in ALCL and IMT. In ALCL, the current goal is to investigate the inclusion of ALK inhibitors in front-line therapy with the aim of decreasing toxicity with higher/similar efficacy compared to present first-line therapies. For IMT, the focus is to develop a joint prospective trial with one product in children, adolescents and adults, taking advantage of the common biology across the age spectrum. As approximately 50% of IMTs are ALK-positive, molecular analysis is required to identify patients to be treated with an ALK inhibitor. For neuroblastoma, crizotinib has not shown robust anti-tumour activity. A focused and sequential development of ALK inhibitors with very good central nervous system (CNS) penetration in CNS tumours with ALK fusions should be undertaken. The Forum reinforced the strong need for global academic collaboration, very early involvement of regulators with studies seeking possible registration and early academia-multicompany engagement. Innovations in study design and conduct and the use of 'real-world data' supporting development in these rare sub-groups of patients for whom randomised clinical trials are not feasible are important initiatives. A focused and sequenced development strategy, where one product is evaluated first with other products being assessed sequentially, is applicable for ALK inhibitors and other medicinal products in children.
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http://dx.doi.org/10.1016/j.ejca.2021.08.022DOI Listing
November 2021

Trends of paediatric head injury and acute care costs in Australia.

J Paediatr Child Health 2021 Sep 15. Epub 2021 Sep 15.

Department of Paediatrics, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Victoria, Australia.

Aim: Paediatric head injuries (PHI) are the most common cause of trauma-related emergency department (ED) presentations. This study sought to report the incidence of PHI in Australia, examine the temporal trends from 2014 to 2018 and estimate the patient and population-level acute care costs.

Methods: Taking a public-sector health-care perspective, we applied direct and indirect hospital costs for PHI-related ED visits and acute admissions. All costs were inflated to 2018 Australian dollars ($). The patient-level analysis was performed with data from 17 841 children <18 years old enrolled in the prospective Australasian Paediatric Head Injury Study. Mechanisms of injury were characterised by the total and average acute care costs. The population-level data of PHI-related ED presentations were obtained from the Independent Hospital Pricing Authority. Age-standardised incidence rates (IR) and incidence rate ratios (IRR) were calculated, and negative binomial regression examined the temporal trend.

Results: The age-standardised IR for PHI was 2734 per 100 000 population in 2018, with a significant increase over 5 years (IRR 1.13, 95% confidence interval (CI) 1.12-1.14; P < 0.001) and acute care costs of $154 million. Falls occurred in 70% of the study cohort, with average costs per episode of $666 (95% CI: $627-$706), accounting for 47% of acute care costs. Transportation-related injuries occurred in 4.1% of the study cohort, with average costs per episode of $8555 (95% CI: $6193-$10 917), accounting for 35% of acute care costs.

Conclusion: PHI have increased significantly in Australia and are associated with substantial acute care costs. Population-based efforts are required for road safety and injury prevention.
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http://dx.doi.org/10.1111/jpc.15699DOI Listing
September 2021

Measurement of Intersectional Microaggressions: Conceptual Barriers and Recommendations.

Perspect Psychol Sci 2021 Sep;16(5):956-971

Department of Psychology, Roosevelt University.

Since Crenshaw coined the term "intersectionality" in 1989, researchers of bias have struggled with how to capture the complexity and intricacies of intersectional identities and microaggressions experienced by individuals holding these identities within the quantitative framework that dominates psychology. Although scholarship has grown in the exploration of experiences such as racialized sexual harassment, or sexual racism within queer and trans communities, there is no strong consensus on how this might be measured systematically in ways that allow for inferences regarding the experiences of populations of interest. With an emphasis on the experiences of queer and trans people of color, this article explores intersectional identities through three main points: First, we define what is meant by intersectionality and the real-world experiences that are important for advancing an understanding of microaggressions; second, we review the existing measures and their ability to capture the breadth and depth of the lived experience of those with intersectional identities; and third, we propose a framework for the development of a more accurate and comprehensive measure of microaggressions.
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http://dx.doi.org/10.1177/1745691621991855DOI Listing
September 2021

Africanized Honey Bee Sting-Induced Stress-Related Cardiomyopathy: A Bee or Octopus Trap.

Cureus 2021 Jul 28;13(7):e16681. Epub 2021 Jul 28.

Cardiology, Eric Williams Medical Sciences Complex, Champs Fleurs, TTO.

The Africanized honey bee commonly referred to as the "killer bee," is a hybrid of the East African lowland honey bee with various European honey bees. These bees tend to be more hostile as compared to other bee species. Their stings may have devastating clinical sequelae, including cardiovascular, cerebrovascular events, and fatalities. We report the first-in-Caribbean case of a middle-aged woman who experienced stress-related, Takotsubo cardiomyopathy (also known as stress-related cardiomyopathy [SRC]) after being afflicted with innumerable Africanized honey bee stings. Key clinical message: The clinician should be cognizant of Takotsubo's cardiomyopathy as a potential sequela of Hymenoptera envenomation and anaphylaxis.
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http://dx.doi.org/10.7759/cureus.16681DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8392821PMC
July 2021

PECARN algorithms for minor head trauma: Risk stratification estimates from a prospective PREDICT cohort study.

Acad Emerg Med 2021 Oct 8;28(10):1124-1133. Epub 2021 Jul 8.

Clinical Sciences, Murdoch Children's Research Institute, Melbourne, Victoria, Australia.

Background: The Pediatric Emergency Care Applied Research Network (PECARN) head trauma clinical decision rules informed the development of algorithms that risk stratify the management of children based on their risk of clinically important traumatic brain injury (ciTBI). We aimed to determine the rate of ciTBI for each PECARN algorithm risk group in an external cohort of patients and that of ciTBI associated with different combinations of high- or intermediate-risk predictors.

Methods: This study was a secondary analysis of a large multicenter prospective data set, including patients with Glasgow Coma Scale scores of 14 or 15 conducted in Australia and New Zealand. We calculated ciTBI rates with 95% confidence intervals (CIs) for each PECARN risk category and combinations of related predictor variables.

Results: Of the 15,163 included children, 4,011 (25.5%) were aged <2 years. The frequency of ciTBI was 8.5% (95% CI = 6.0%-11.6%), 0.2% (95% CI = 0.0%-0.6%), and 0.0% (95% CI = 0.0%-0.2%) in the high-, intermediate-, and very-low-risk groups, respectively, for children <2 years and 5.7% (95% CI = 4.4%-7.2%), 0.7% (95% CI = 0.5%-1.0%), and 0.0% (95% CI = 0.0%-0.1%) in older children. The isolated high-risk predictor with the highest risk of ciTBI was "signs of palpable skull fracture" for younger children (11.4%, 95% CI = 5.3%-20.5%) and "signs of basilar skull fracture" in children ≥2 years (11.1%, 95% CI = 3.7%-24.1%). For older children in the intermediate-risk category, the presence of all four predictors had the highest risk of ciTBI (25.0%, 95% CI = 0.6%-80.6%) followed by the combination of "severe mechanism of injury" and "severe headache" (7.7%, 95% CI = 0.2%-36.0%). The very few children <2 years at intermediate risk with ciTBI precluded further analysis.

Conclusions: The risk estimates of ciTBI for each of the PECARN algorithms risk group were consistent with the original PECARN study. The risk estimates of ciTBI within the high- and intermediate-risk predictors will help further refine clinical judgment and decision making on neuroimaging.
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http://dx.doi.org/10.1111/acem.14308DOI Listing
October 2021

Isolated Right Ventricular Noncompaction Cardiomyopathy Causing Pulmonary Embolism.

J Investig Med High Impact Case Rep 2021 Jan-Dec;9:23247096211024027

University of the West Indies, St. Augustine, Trinidad and Tobago.

Ventricular noncompaction is a rare, heterogeneous cardiomyopathy characterized by marked trabeculations and deep intertrabecular spaces with clinical sequelae of heart failure, arrhythmias, and cardioembolic events. In this article, we describe a patient with isolated right ventricular noncompaction who presented with submassive pulmonary embolism, which was managed with long-term direct oral anticoagulation.
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http://dx.doi.org/10.1177/23247096211024027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8207261PMC
October 2021

Diffusion Tensor Imaging Correlates of Concussion Related Cognitive Impairment.

Front Neurol 2021 24;12:639179. Epub 2021 May 24.

Department of Neurology, University of Texas McGovern Medical School, Houston, TX, United States.

Cognitive impairment after concussion has been widely reported, but there is no reliable imaging biomarker that predicts the severity of cognitive decline post-concussion. This study tests the hypothesis that patients with a history of concussion and persistent cognitive impairment have fractional anisotropy (FA) and mean diffusivity (MD) values from diffusion tensor imaging (DTI) that are specifically associated with poor performance on the Montreal Cognitive Assessment (MoCA). Fifty-three subjects (19 females) with concussions and persistent cognitive symptoms had MR imaging and the MoCA. Imaging was analyzed by atlas-based, whole-brain DTI segmentation and FLAIR lesion segmentation. Then, we conducted a random forest-based recursive feature elimination (RFE) with 10-fold cross-validation on the entire dataset, and with partial correlation adjustment for age and lesion load. RFE showed that 11 DTI variables were found to be important predictors of MoCA scores. Partial correlation analyses, corrected for age and lesion load, showed significant correlations between MoCA scores and right fronto-temporal regions: inferior temporal gyrus MD ( = -0.62, = 0.00001), middle temporal gyrus MD ( = -0.54, = 0.0001), angular gyrus MD ( = -0.48, = 0.0008), and inferior frontal gyrus FA ( = 0.44, = 0.002). This is the first study to demonstrate a correlation between MoCA scores and DTI variables in patients with a history of concussion and persistent cognitive impairment. This kind of research will significantly increase our understanding of why certain persons have persistent cognitive changes after concussion which, in turn, may allow us to predict persistent impairment after concussion and suggest new interventions.
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http://dx.doi.org/10.3389/fneur.2021.639179DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8180854PMC
May 2021

Neuroradiology of infectious diseases.

Curr Opin Infect Dis 2021 06;34(3):228-237

Section of Infectious Diseases, UT Health McGovern Medical School, Houston, Texas, USA.

Purpose Of Review: Early diagnosis of central nervous system (CNS) infections is crucial given high morbidity and mortality. Neuroimaging in CNS infections is widely used to aid in the diagnosis, treatment and to assess the response to antibiotic and neurosurgical interventions.

Recent Findings: The Infectious Diseases Society of America (IDSA) guidelines have clear recommendations for obtaining a computerized tomography of the head (CTH) prior to lumbar puncture (LP) in suspected meningitis. In the absence of indications for imaging or in aseptic meningitis, cranial imaging is of low utility. In contrast, cranial imaging is of utmost importance in the setting of encephalitis, bacterial meningitis, ventriculitis, bacterial brain abscess, subdural empyema, epidural abscess, neurobrucellosis, neurocysticercosis, and CNS tuberculosis that can aid clinicians with the differential diagnosis, source of infection (e.g., otitis, sinusitis), assessing complications of meningitis (e.g., hydrocephalus, venous sinus thrombosis, strokes), need for neurosurgical interventions and to monitor for the response of therapy. Novel imaging techniques such as fast imaging employing steady-state acquisition (FIESTA), susceptibility-weighted imaging (SWI), and chemical exchange saturation transfer (CEST) contrast are briefly discussed.

Summary: Though the radiological findings in CNS infections are vast, certain patterns along with clinical clues from history and examination often pave the way to early diagnosis. This review reiterates the importance of obtaining cranial imaging when necessary, and the various radiological presentations of commonly encountered CNS infections.
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http://dx.doi.org/10.1097/QCO.0000000000000725DOI Listing
June 2021

Pathogenesis of COVID-19, Disease Outbreak: A Review.

Curr Pharm Biotechnol 2021 ;22(12):1591-1601

Institute of Pharmaceutical Research GLA University, 17km Stone, NH-2, Mathura-Delhi Road Mathura, Chaumuhan, Uttar Pradesh-281406, India.

Coronavirus-19 is a severe acute respiratory disorder in humans which has become a major health problem. It spreads out very rapidly throughout the world since it has been first identified in Wuhan, China (December 2019). The causative virus is known as severe acute respiratory syndrome coronavirus 2. And the World Health Organization has named this respiratory syndrome as a new epidemic disease called COVID-19. The incidence of COVID-19 continued to increase with three million confirmed infected cases and with 244,000 death cases worldwide. Until now there is no specific treatment or vaccine available against COVID- 19. The collective information about the different aspects of COVID-19 viral infection has been gathered from renowned journals, and electronic databases including Science Direct, Web of Science, Scopus and PubMed from 1990 to 2020. This manuscript has highlighted the transmission and symptoms of Covid-19. Therefore, these studies show how the SARS-CoV 2 can facilitate the debut of the virus into targeted host cells.
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http://dx.doi.org/10.2174/1389201022666210127113441DOI Listing
September 2021

PRISMA Based Systematic Review: Pharmacognostic Study of Zanthoxylum armatum DC.

Mini Rev Med Chem 2021 ;21(14):1965-1997

Institute of Pharmaceutical Research, GLA University, Mathura-281406, Uttar Pradesh, India.

Introduction: Herb, Zanthoxylum armatum DC., commonly called Indian prickly ash, and Nepal pepper (family Rutaceae), is widely utilized in the traditional medicinal system.

Objective: The current review provides requisite data for collecting descriptive information on the organoleptic, microscopical, ethnobotanical use, and phytochemicals and pharmacological properties of Z. armatum; therefore, it may help in forming a bridge between research gaps and the upcoming future findings for most of the researches.

Materials And Methods: The systematic literature survey was conducted using the PRISMA methodology. The collective information was gathered from books, renowned journals, and electronic databases including Science Direct, Web of Science, Scopus and PubMed from 1966 to 2020.

Results: Most of the bioactive metabolites are isolated and characterized till date, such as monoterpenes in essential oil and lignan components are reported to be present in the herbs. Several in vitro and in vivo pharmacological bioassays revealed the potential of Z. armatum having as possessing antimicrobial, antifungal, antibacterial, and hepatoprotective effects and so on.

Conclusion: Therefore, the current review summarizes the organoleptic, microscopy, phytochemistry and biological activities of Z. armatum, providing more emphasis on in vitro as well as in-vivo studies along with clinical research, helpful in exploring the potential efficacy of the plant.
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http://dx.doi.org/10.2174/1389557521999201230200503DOI Listing
October 2021

FDA Approval Summary: Lurbinectedin for the Treatment of Metastatic Small Cell Lung Cancer.

Clin Cancer Res 2021 May 7;27(9):2378-2382. Epub 2020 Dec 7.

Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.

On June 15, 2020, the FDA granted accelerated approval to lurbinectedin for the treatment of adult patients with metastatic small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy. Approval was granted on the basis of the clinically meaningful effects on overall response rate (ORR) and duration of response (DOR), and the safety profile observed in a multicenter, open-label, multicohort clinical trial (PM1183-B-005-14, NCT02454972), referred to as Study B-005, in patients with advanced solid tumors. The trial included a cohort of 105 patients with metastatic SCLC who had disease progression on or after platinum-based chemotherapy. The confirmed ORR determined by investigator assessment using RECIST 1.1 in the approved SCLC patient population was 35% [95% confidence interval (CI): 26-45], with a median DOR of 5.3 (95% CI: 4.1-6.4) months. The drug label includes warnings and precautions for myelosuppression, hepatotoxicity, and embryo-fetal toxicity. This is the first drug approved by the FDA in over 20 years in the second line for patients with metastatic SCLC. Importantly, this approval includes an indication for patients who have platinum-resistant disease, representing an area of particular unmet need.
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http://dx.doi.org/10.1158/1078-0432.CCR-20-3901DOI Listing
May 2021

A high-throughput screening identifies ZNF418 as a novel regulator of the ubiquitin-proteasome system and autophagy-lysosomal pathway.

Autophagy 2021 Oct 27;17(10):3124-3139. Epub 2020 Dec 27.

Institute of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

The ubiquitin-proteasome system (UPS) and autophagy-lysosomal pathway (ALP) are two major protein degradation pathways in eukaryotic cells. Initially considered as two independent pathways, there is emerging evidence that they can work in concert. As alterations of UPS and ALP function can contribute to neurodegenerative disorders, cancer and cardiac disease, there is great interest in finding targets that modulate these catabolic processes. We undertook an unbiased, total genome high-throughput screen to identify novel effectors that regulate both the UPS and ALP. We generated a stable HEK293 cell line expressing a UPS reporter (Ub-mCherry) and an ALP reporter (GFP-LC3) and screened for genes for which knockdown increased both Ub-mCherry intensity and GFP-LC3 puncta. With stringent selection, we isolated 80 candidates, including the transcription factor ZNF418 (ZFP418 in rodents). After screen validation with overexpression in HEK293 cells, we evaluated knockdown and overexpression in neonatal rat ventricular myocytes (NRVMs). Endogenous and overexpressed ZFP418 were localized in the nucleus. Subsequent experiments showed that ZFP418 negatively regulates UPS and positively regulates ALP activity in NRVMs. RNA-seq from knockdown revealed altered gene expression of numerous ubiquitinating and deubiquitinating enzymes, decreased expression of autophagy activators and initiators and increased expression of autophagy inhibitors. We found that ZPF418 activated the promoters of and , which are involved in autophagy. RNA-seq from knockdown revealed accumulation of several genes involved in cardiac development and/or hypertrophy. In conclusion, our study provides evidence that ZNF418 activates the ALP, inhibits the UPS and regulates genes associated with cardiomyocyte structure/function. ACTN2, actinin alpha 2; ALP, autophagy-lysosomal pathway; COPB1, COPI coat complex subunit beta 1; DAPK2, death associated protein kinase 2; FYCO1, FYVE and coiled-coil domain autophagy adaptor 1; HEK293, human embryonic kidney cells 293; HTS, high-throughput screen; LC3, microtubule associated protein 1 light chain 3; NRVMs, neonatal rat ventricular myocytes; RNA-seq, RNA sequencing; RPS6, ribosomal protein S6; TNNI3, troponin I, cardiac 3; UPS, ubiquitin-proteasome system; shRNA, short hairpin RNA; SQSTM1/p62, sequestosome 1; VPS28, VPS28 subunit of ESCRT-I; ZNF418/ZFP418, zinc finger protein 418.
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http://dx.doi.org/10.1080/15548627.2020.1856493DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8526018PMC
October 2021

Esophageal cancer as initial presentation of Fanconi anemia in patients with a hypomorphic variant.

Cold Spring Harb Mol Case Stud 2020 12 17;6(6). Epub 2020 Dec 17.

Laboratory of Genome Maintenance, The Rockefeller University, New York, New York, 10065 USA.

Fanconi anemia (FA) is a clinically heterogenous and genetically diverse disease with 22 known complementation groups (FA-A to FA-W), resulting from the inability to repair DNA interstrand cross-links. This rare disorder is characterized by congenital defects, bone marrow failure, and cancer predisposition. is the most commonly mutated gene in FA and a variety of mostly private mutations have been documented, including small and large indels and point and splicing variants. Genotype-phenotype associations in FA are complex, and a relationship between particular variants and the observed cellular phenotype or illness severity remains unclear. In this study, we describe two siblings with compound heterozygous variants (c.3788_3790delTCT and c.4199G > A) who both presented with esophageal squamous cell carcinoma at the age of 51. The proband came to medical attention when he developed pancytopenia after a single cycle of low-dose chemotherapy including platinum-based therapy. Other than a minor thumb abnormality, neither patient had prior findings to suggest FA, including normal blood counts and intact fertility. Patient fibroblasts from both siblings display increased chromosomal breakage and hypersensitivity to interstrand cross-linking agents as seen in typical FA. Based on our functional data demonstrating that the c.4199G > A/p.R1400H variant represents a hypomorphic allele, we conclude that the residual activity of the Fanconi anemia repair pathway accounts for lack of spontaneous bone marrow failure or infertility with the late presentation of malignancy as the initial disease manifestation. This and similar cases of adult-onset esophageal cancer stress the need for chromosome breakage testing in patients with early onset of aerodigestive tract squamous cell carcinomas before platinum-based therapy is initiated.
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http://dx.doi.org/10.1101/mcs.a005595DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7784490PMC
December 2020

Self-Emulsifying Drug Delivery System (SEDDS): An Emerging Dosage Form to Improve the Bioavailability of Poorly Absorbed Drugs.

Crit Rev Ther Drug Carrier Syst 2020 ;37(4):305-329

Institute of Pharmaceutical Research, GLA University, Mathura (U.P), India.

The main objective of drug(s) formulation is to enhance the bioavailability of the drug within the body. Some of the challenging issues associated with poorly water-soluble drugs concern solubility and bioavailability factors. To overcome these problems, new technologies, such as lipid-based drug delivery systems including micro or nano emulsifying drug delivery system, have gained importance in recent years, due to their enhanced solubility and bioavailability in the gastrointestinal tract. Such systems are incorporated or solubilized within the lipid excipients or mixed with oils or surfactants/co-solvents to facilitate the solubility and absorption rate, which can enhance the bioavailability of the targeted drug. This review provides a comprehensive summary about the properties, factors affecting formulations, excipients, formulation techniques, and characterization of self-emulsifying drug delivery systems. It also focuses on the new approaches concerned with SEDDS.
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http://dx.doi.org/10.1615/CritRevTherDrugCarrierSyst.2020033111DOI Listing
June 2021

Carissa carandas L. - phyto-pharmacological review.

J Pharm Pharmacol 2020 Dec 29;72(12):1694-1714. Epub 2020 Jul 29.

Institute of Pharmaceutical Research, GLA University, Mathura, Uttar Pradesh, India.

Objectives: Carissa carandas is an evergreen thorny shrub (Apocynaceae family), commonly, known as karonda. It has small berry-shaped fruits, used as additive in many pickles or as a spice in northern India.

Methods: The present review covers the literature survey from 1968 to 2020. The data have been collected from various journals, books, thesis and some of the electronic search via Internet-based information such as PubMed, Google Scholar, ScienceDirect, EBSCO, online electronic journals, SpringerLink, Wiley and Ayush.

Key Findings: From literature survey, it has been found that the herbal drug contains wide variety of flavonoids, phenolic acids, steroids, volatile oils, lignans, alkaloids, polysaccharides and so on. These phytochemicals exhibit a range of pharmacological activities including antioxidant, anti-inflammatory, antidiabetic, antimicrobial and antifungal properties.

Conclusions: This current review offers primary data for further research work. The in-vitro evaluations as well as in-vivo models/experiments have provided a biosynthetic observation for its various ethno-pharmacological uses and even pharmacological properties. This review would provide all valuable information which will be beneficiary to conduct some important pharmacokinetic and toxicological research works on human models with respect to ensure the effects of active ingredients in the body and even to validate its safety issues in clinical aspects.
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http://dx.doi.org/10.1111/jphp.13328DOI Listing
December 2020

Ameliorates Acetic Acid-induced Rat Gastric Ulcer.

J Diet Suppl 2021 25;18(3):278-292. Epub 2020 May 25.

Division of Pharmacology, Institute of Pharmaceutical Research, GLA University, Mathura, India.

(Roxb; Family:sapotaceae) is reported to exert preventive effect in several experimental ulcer models. However, there is no report of on gastric ulcer healing property. Thus, the present study was designed to evaluate the gastric ulcer healing activity of methanolic stem bark extract of (MH) and to derive a plausible molecular level of mechanism of action. MH was subjected to several phytochemical screening tests and standardized to quercetin by HPTLC. In the first pharmacological experiment, the standardized MH (50, 100 and 200 mg/kg) was carried out for ulcer healing activity against acetic acid (AA)-induced gastric ulcer in male rats. MH (100 and 200 mg/kg) ameliorated AA-induced rat gastric lesions. Further, MH (100 and 200 mg/kg) attenuated AA-induced changes in the levels of lipid peroxidation (LPO), reduced glutathione (GSH), oxidized glutathione (GSSG) and ratio of GSH/GSSG and activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) enzymes, and level of hame oxygenase-1 (HO-1) in stomach tissue. In the subsequent set of experiment, trigonelline (30 mg/kg; p.o.), a potent Nrf2 antagonist, significantly abrogated the gastric ulcer healing activity of MH (100 mg/kg) in AA challenged animals. Further, trigonelline attenuated the effects of MH (100 mg/kg) on the levels of LPO, GSH, GSSG and ratio of GSH/GSSG and activity of SOD, CAT, GPx and GR enzymes, and level of HO-1 in AA challenged rodents. These observations implicate the fact that MH could be a better therapeutic alternative in the management of gastric ulcer.
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http://dx.doi.org/10.1080/19390211.2020.1770393DOI Listing
September 2021

First Mildly Ill, Nonhospitalized Case of Coronavirus Disease 2019 (COVID-19) Without Viral Transmission in the United States-Maricopa County, Arizona, 2020.

Clin Infect Dis 2020 07;71(15):807-812

Maricopa County Department of Public Health, Phoenix, Arizona, USA.

Background: Coronavirus disease 2019 (COVID-19) causes a range of illness severity. Mild illness has been reported, but whether illness severity correlates with infectivity is unknown. We describe the public health investigation of a mildly ill, nonhospitalized COVID-19 case who traveled to China.

Methods: The case was a Maricopa County resident with multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive specimens collected on 22 January 2020. Contacts were persons exposed to the case on or after the day before case diagnostic specimen collection. Contacts were monitored for 14 days after last known exposure. High-risk contacts had close, prolonged case contact (≥ 10 minutes within 2 m). Medium-risk contacts wore all US Centers for Disease Control and Prevention-recommended personal protective equipment during interactions. Nasopharyngeal and oropharyngeal (NP/OP) specimens were collected from the case and high-risk contacts and tested for SARS-CoV-2.

Results: Paired case NP/OP specimens were collected for SARS-CoV-2 testing at 11 time points. In 8 pairs (73%), ≥ 1 specimen tested positive or indeterminate, and in 3 pairs (27%) both tested negative. Specimens collected 18 days after diagnosis tested positive. Sixteen contacts were identified; 11 (69%) had high-risk exposure, including 1 intimate contact, and 5 (31%) had medium-risk exposure. In total, 35 high-risk contact NP/OP specimens were collected for SARS-CoV-2 testing; all 35 pairs (100%) tested negative.

Conclusions: This report demonstrates that SARS-CoV-2 infection can cause mild illness and result in positive tests for up to 18 days after diagnosis, without evidence of transmission to close contacts. These data might inform public health strategies to manage individuals with asymptomatic infection or mild illness.
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http://dx.doi.org/10.1093/cid/ciaa374DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7184399PMC
July 2020

Dementia Diagnosis in Seven Languages: The Addenbrooke's Cognitive Examination-III in India.

Arch Clin Neuropsychol 2020 Jul;35(5):528-538

Department of Neurology, National Institute of Mental Health and Neurosciences, Bengaluru, India.

Objective: With the rising burden of dementia globally, there is a need to harmonize dementia research across diverse populations. The Addenbrooke's Cognitive Examination-III (ACE-III) is a well-established cognitive screening tool to diagnose dementia. But there have been few efforts to standardize the use of ACE-III across cohorts speaking different languages. The present study aimed to standardize and validate ACE-III across seven Indian languages and to assess the diagnostic accuracy of the test to detect dementia and mild cognitive impairment (MCI) in the context of language heterogeneity.

Methods: The original ACE-III was adapted to Indian languages: Hindi, Telugu, Kannada, Malayalam, Urdu, Tamil, and Indian English by a multidisciplinary expert group. The ACE-III was standardized for use across all seven languages. In total, 757 controls, 242 dementia, and 204 MCI patients were recruited across five cities in India for the validation study. Psychometric properties of adapted versions were examined and their sensitivity and specificity were established.

Results: The sensitivity and specificity of ACE-III in identifying dementia ranged from 0.90 to 1, sensitivity for MCI ranged from 0.86 to 1, and specificity from 0.83 to 0.93. Education but not language was found to have an independent effect on ACE-III scores. Optimum cut-off scores were established separately for low education (≤10 years of education) and high education (>10 years of education) groups.

Conclusions: The adapted versions of ACE-III have been standardized and validated for use across seven Indian languages, with high diagnostic accuracy in identifying dementia and MCI in a linguistically diverse context.
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http://dx.doi.org/10.1093/arclin/acaa013DOI Listing
July 2020

Faculty's perspective on skill assessment in undergraduate medical education: Qualitative online forum study.

J Educ Health Promot 2020 30;9:20. Epub 2020 Jan 30.

Department of Pharmacology, Christian Medical College, Ludhiana, Punjab, India.

Background: India is at the nascent stage of competency-based medical education. Faculties trained in medical education are the main driving force for change. The present study explores the perception of faculties about the current practices and problems in medical/dental/nursing undergraduate assessment, barriers to adoption of best practices, and solutions for addressing them.

Methodology: A qualitative study was designed and data collected through an asynchronous online discussion forum. A group of 31 health professionals (FAIMER fellows selected on the basis of active participation in department of medical education of respective colleges) participated in the forum. An open-ended topic guide with prompts was designed. The forum was initiated by release of discussion topics (threads) at the start of the month and remained in forum throughout the month. Researchers moderated and recorded day-to-day events. All online forum data were coded line by line and analyzed using conventional content analysis.

Results: Four categories generated were: (1) Low utility of current skill assessment system due to low validity and reliability; (2) Barrier in adopting newer assessment tool due to the absence of felt need of faculties and students, mistaken beliefs, and limited resources; (3) Poor implementation of newer assessment tools such as formatives and objective structured clinical examination with no blueprinting; and (4) Solutions proposed were regular formative assessment, criterion-based examination, quality-assured faculty development programs, and administrative support.

Conclusions: Barriers in adopting newer assessment tools are related to the faculty's perception and resource constraint. This can be addressed by quality-assured faculty development programs and effective implementation of competency-based education.
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http://dx.doi.org/10.4103/jehp.jehp_390_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7034168PMC
January 2020

Psychometric evaluation of the Functional Analytic Psychotherapy Intimacy Scale in obsessive-compulsive and related disorders.

Bull Menninger Clin 2020 26;84(2):156-179. Epub 2020 Feb 26.

Professor, Department of Psychology, Bowling Green State University, Bowling Green, Ohio.

Functional Analytic Psychotherapy (FAP) is a contextual behavioral therapy that targets specific ideographic behaviors related to interpersonal functioning and intimacy. There is a scarcity of measures specifically focused on behavioral measurement of intimacy as well as limited studies that examine intimacy in obsessive-compulsive and related disorders (OCRDs). Leonard and colleagues (2014) created the Functional Analytic Psychotherapy Intimacy Scale (FAPIS). The purpose of this study was to investigate the validity of the FAPIS in evaluating those with OCRDs. The FAPIS and other measures of intimacy were administered to 549 nonreferred adults endorsing OCRD symptoms. Several confirmatory factor analyses were conducted to assess the best fitting factor structure, and convergent validity and divergent validity were also assessed. Given the psychometric properties of the FAPIS in this sample, future research may be helpful in assessing if the FAPIS would be beneficial in measuring change related to intimacy when working with people with OCRDs.
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http://dx.doi.org/10.1521/bumc_2020_84_06DOI Listing
January 2021

Is Desmin Propensity to Aggregate Part of its Protective Function?

Cells 2020 02 20;9(2). Epub 2020 Feb 20.

Center for Research on Cardiac Intermediate Filaments, Johns Hopkins University, Baltimore, MD 21205, USA.

Desmin is the major protein component of the intermediate filaments (IFs) cytoskeleton in muscle cells, including cardiac. The accumulation of cleaved and misfolded desmin is a cellular hallmark of heart failure (HF). These desmin alterations are reversed by therapy, suggesting a causal role for the IFs in the development of HF. Though IFs are known to play a role in the protection from stress, a mechanistic model of how that occurs is currently lacking. On the other hand, the heart is uniquely suited to study the function of the IFs, due to its inherent, cyclic contraction. That is, HF can be used as a model to address how IFs afford protection from mechanical, and possibly redox, stress. In this review we provide a brief summary of the current views on the function of the IFs, focusing on desmin. We also propose a new model according to which the propensity of desmin to aggregate may have been selected during evolution as a way to dissipate excessive mechanical and possibly redox stress. According to this model, though desmin misfolding may afford protection from acute injury, the sustained or excessive accumulation of desmin aggregates could impair proteostasis and contribute to disease.
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http://dx.doi.org/10.3390/cells9020491DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072738PMC
February 2020

Open Letter to a Burned-Out Intern.

Authors:
Sonia Singh

Ann Intern Med 2020 02;172(4):289-290

Memorial Hermann Medical Group, Houston, Texas (S.S.).

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http://dx.doi.org/10.7326/M19-2668DOI Listing
February 2020

The Effect of Patient Observation on Cranial Computed Tomography Rates in Children With Minor Head Trauma.

Acad Emerg Med 2020 09 26;27(9):832-843. Epub 2020 Mar 26.

From the, Murdoch Children's Research Institute, Melbourne, Australia.

Background: Management of children with minor blunt head trauma often includes a period of observation to determine the need for cranial computed tomography (CT). Our objective was to estimate the effect of planned observation on CT use for each Pediatric Emergency Care Applied Research Network (PECARN) traumatic brain injury (TBI) risk group among children with minor head trauma.

Methods: This was a secondary analysis of a prospective observational study at 10 emergency departments (EDs) in Australia and New Zealand, including 18,471 children < 18 years old, presenting within 24 hours of blunt head trauma, with Glasgow Coma Scale scores of 14 to 15. The planned observation cohort was defined by those with planned observation and no immediate plan for cranial CT. The comparison cohort included the rest of the patients who were either not observed or for whom a decision to obtain a cranial CT was made immediately after ED assessment. The outcome clinically important TBI (ciTBI) was defined as death due to head trauma, neurosurgery, intubation for > 24 hours for head trauma, or hospitalization for ≥ 2 nights in association with a positive cranial CT scan. We estimated the odds of cranial CT use with planned observation, adjusting for patient characteristics, PECARN TBI risk group, history of seizure, time from injury, and hospital clustering, using a generalized linear model with mixed effects.

Results: The cranial CT rate in the total cohort was 8.6%, and 0.8% had ciTBI. The planned observation group had 4,945 (27%) children compared to 13,526 (73%) in the no planned observation group. Cranial CT use was significantly lower with planned observation (adjusted odds ratio [OR] = 0.2, 95% confidence interval [CI] = 0.1 to 0.1), with no difference in missed ciTBI rates. There was no difference in the odds of cranial CT use with planned observation for the group at very low risk for ciTBI (adjusted OR = 0.9, 95% CI = 0.5 to 1.4). Planned observation was associated with significantly lower cranial CT use in patients at intermediate risk (adjusted OR = 0.2, 95% CI = 0.2 to 0.3) and high risk (adjusted OR = 0.1, 95% CI = 0.0 to 0.1) for ciTBI.

Conclusions: Even in a setting with low overall cranial CT rates in children with minor head trauma, planned observation was associated with decreased cranial CT use. This strategy can be safely implemented on selected patients in the PECARN intermediate- and higher-risk groups for ciTBI.
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http://dx.doi.org/10.1111/acem.13942DOI Listing
September 2020

Hair pulling antecedents in trichotillomania: Their relationship with experiential avoidance.

Bull Menninger Clin 2020 15;84(1):35-52. Epub 2020 Jan 15.

Department of Psychology at Marquette University, Milwaukee, Wisconsin.

In this study, 285 adults who met criteria for trichotillomania (TTM) via self-report completed an online, cross-sectional survey examining antecedent phenomenological experiences pertaining to hair pulling along with measures of TTM severity and experiential avoidance (i.e., avoidance of or escape from unwanted thoughts or feelings). Results showed a heterogeneous depiction of antecedent experiences. Subsequent analyses revealed that certain antecedents were not significantly related to TTM severity but were significantly correlated with higher levels of experiential avoidance. In particular, four of five classes of antecedents (i.e., bodily sensations, physical symptoms, mental anxiety, and general uncomfortableness) were significantly related to greater experiential avoidance. The authors conclude that treatments may need to be designed to address specific private antecedents, and that this may be done through targeting experiential avoidance.
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http://dx.doi.org/10.1521/bumc_2020_84_01DOI Listing
December 2020

Breaking the cycle of recurrent fracture: implementing the first fracture liaison service (FLS) in British Columbia, Canada.

Arch Osteoporos 2019 11 27;14(1):116. Epub 2019 Nov 27.

Fraser Health Authority, Surrey, British Columbia, Canada.

Fractures occurring with very little trauma are often caused by osteoporosis and can lead to disability. This study demonstrates that a coordinator working with an orthopaedic team can significantly increase the number of individuals receiving appropriate treatments during their after-fracture care to prevent future fractures from occurring.

Purpose: Well-implemented Fracture Liaison Service (FLS) programs increase appropriate investigation and treatment for osteoporosis after low trauma fracture. This research evaluates the effectiveness of the first FLS program implemented in British Columbia (BC), Canada.

Methods: A controlled before-and-after study was conducted. The intervention was an FLS program implemented at an orthopaedic outpatient clinic at Peace Arch Hospital in BC. Eligible patients were those over the age of 50 years with a low trauma fracture of the hip, pelvis, vertebra, wrist or humerus. A nurse practitioner FLS coordinator identified, investigated and initiated treatment in patients based on their future fracture risk. The primary outcome was the percentage of all patients at high-risk to refracture, who achieved at least one of the following outcomes: (1) started on osteoporosis medication, (2) referred to an osteoporosis consultant or (3) assessed for treatment change if they were already on osteoporosis medication at the time of the fracture. Secondary outcomes included the rate of bone density testing, referral to fall prevention programs and change in health-related quality of life over 6 months.

Results: A total of 195 patients participated in the study (65 in the usual care group, 130 in the FLS group). Average age was 70.5 years (standard deviation 11.5), and 84% of participants were female. In the FLS group, 77.8% of high-risk patients achieved the primary outcome compared with 22.9% in the usual care group.

Conclusion: In BC, the implementation of an FLS program improved investigation and treatment for osteoporosis after low trauma fracture.
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http://dx.doi.org/10.1007/s11657-019-0662-6DOI Listing
November 2019

The mindful attention and awareness scale is associated with lower levels of high-frequency heart rate variability in a laboratory context.

Psychophysiology 2020 03 17;57(3):e13506. Epub 2019 Nov 17.

Department of Psychology, Bowling Green State University, Bowling Green, Ohio.

Trait mindfulness has been associated with well-being. A key component of trait mindfulness is intentional attention and awareness which is most commonly measured by the Mindful Attention and Awareness Scale (MAAS). This study investigated the relationship between the MAAS and cardiovascular (HF-HRV, heart rate) reactivity to two laboratory stressors that evoked different patterns of change in heart rate (HR). One stressor (viewing a video of a surgery) evoked HR deceleration while the other stressor (mental arithmetic) evoked HR acceleration. Undergraduate students completed the MAAS and were then exposed to the two stressors while ECG (electrocardiography) was recorded. Findings support the reliability of the stressors to induce expected differential cardiovascular responses and explicate the role of parasympathetic activation. Further, a main effect for MAAS was observed indicating that across laboratory conditions, persons scoring higher on the MAAS had lower HF-HRV relative to persons scoring lower on the MAAS. These findings suggest that higher levels of intentional attention and awareness in a laboratory context might promote parasympathetic withdrawal because these participants were more vigilant, experienced higher cognitive load, and detected more threat cues. Implications for the MAAS and cardiovascular responses to stress are discussed.
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http://dx.doi.org/10.1111/psyp.13506DOI Listing
March 2020

Re: Choosing the discount rate in an economic analysis.

Emerg Med Australas 2019 10 4;31(5):899-900. Epub 2019 Aug 4.

Center for Heathcare Policy and Research, University of California at Davis, Sacramento, California, USA.

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http://dx.doi.org/10.1111/1742-6723.13369DOI Listing
October 2019

Review article: A primer for clinical researchers in the emergency department: Part X. Understanding economic evaluation alongside emergency medicine research.

Emerg Med Australas 2019 10 24;31(5):710-714. Epub 2019 Jun 24.

Center for Heathcare Policy and Research, University of California at Davis, Sacramento, California, USA.

In this series we address research topics in emergency medicine. While traditionally there was an almost exclusive focus on the efficacy and effectiveness of interventions in emergency research, analysis of the costs and the societal impact of different approaches and pathways have become increasingly important. In this paper we will address what health economics means and discuss the different types and key features of economic evaluation relevant for clinical researchers.
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http://dx.doi.org/10.1111/1742-6723.13320DOI Listing
October 2019

A Clinical Score to Support Antiretroviral Management of HIV-exposed Infants on the Day of Birth.

Pediatr Infect Dis J 2019 09;38(9):939-943

From the Epidemiology Branch.

Background: The benefits of combination antiretroviral (ARV) prophylaxis for infants whose HIV exposure is recognized near birth have been established, and the benefits of early ARV therapy are well known. Decisions about ARVs can be supported by the probability that the child has acquired HIV.

Methods: Using 2005-2010 data from Enhanced Perinatal Surveillance of the Centers for Disease Control and Prevention, we developed a tool for use at birth to help predict HIV acquisition of HIV-exposed infants to support ARV management. A logistic regression model, fit using a fully Bayesian approach, was used to determine maternal variables predictive of infant HIV acquisition. We created a score index from these variables, established the sensitivity and specificity of each possible score, and determined the distribution of scores among infants, with and without HIV, in our study population.

Results: Multivariable analysis of data from 8740 HIV-exposed infants (176 infected and 8564 uninfected) yielded 4 maternal variables in the perinatal HIV acquisition prediction model: sexually transmitted infection, substance use, last HIV viral load before delivery and ARV use. Using the regression coefficient estimates, we rescaled each possible score to make the maximum score equal to 100. For each score, sensitivity and specificity were determined; the area under the receiver operating characteristic curve was 0.79. Median index scores for infants with HIV and without HIV were 43 (first quartile 27 and third quartile 60), and 12 (first quartile, 0 and thirs quartile, 29), respectively.

Conclusions: Decisions to begin infants on 3 ARVs-whether considered therapeutic or prophylactic-can be supported by data available on the day of birth.
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http://dx.doi.org/10.1097/INF.0000000000002374DOI Listing
September 2019

Autophagy in cardiomyopathies.

Biochim Biophys Acta Mol Cell Res 2020 03 1;1867(3):118432. Epub 2019 Mar 1.

Institute of Experimental Pharmacology and Toxicology, University Medical Center Hamburg, Hamburg, Germany; German Centre for Cardiovascular Research, Partner Site Hamburg/Kiel/Lübeck, Hamburg, Germany. Electronic address:

Autophagy (greek auto: self; phagein: eating) is a highly conserved process within eukaryotes that degrades long-lived proteins and organelles within lysosomes. Its accurate and constant operation in basal conditions ensures cellular homeostasis by degrading damaged cellular components and thereby acting not only as a quality control but as well as an energy supplier. An increasing body of evidence indicates a major role of autophagy in the regulation of cardiac homeostasis and function. In this review, we describe the different forms of mammalian autophagy, their regulations and monitoring with a specific emphasis on the heart. Furthermore, we address the role of autophagy in several forms of cardiomyopathy and the options for therapy.
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http://dx.doi.org/10.1016/j.bbamcr.2019.01.013DOI Listing
March 2020
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