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Parkinson's disease (PD) is a chronic, progressive neurodegenerative disease with unknown etiology. Some previous studies suggest that elevated serum homocysteine level is a risk factor for stroke, ischemic heart disease; atherosclerosis and neurodegenerative diseases like Parkinson's disease. Serum homocysteine level relates with Parkinson's disease through various mechanisms including gene defect, apoptosis, oxidative stress and DNA damage. Some recent studies reveal that serum homocysteine level is elevated in Parkinson's disease patient compared to healthy individuals. This study was aimed to compare the serum homocysteine level in Parkinson's disease patients and age and sex matched apparently healthy individuals. This was a case control study which was conducted in Department of Neurology and Medicine, Mymensingh Medical College Hospital, Mymensingh during November 2019 to April 2021. Total 55 cases of Parkinson's disease patients and age and sex matched 55 apparently healthy controls were enrolled in this study. Demographics and clinical data were collected using structured case record form and adopting purposive type of sampling method. Serum homocysteine level was measured in both case and control groups. The study reveals that, average age of the patients and control group was in sixth decade. Male predominance was found with male to female ratio was 1.5:1 in case group. Both groups showed almost similar demographic profiles. Twenty-nine (52.72%) patients of Parkinson's disease observed higher serum homocysteine level in contrast to only 8(14.54%) in control group. The mean serum homocysteine ±SD was 15.43±6.04µmol/L in case group and 10.04±5.31µmol/L in control group; the difference was statistically significant (p=0.001). Mean serum homocysteine levels were measured progressively higher with increased duration and advanced stages of disease. It was concluded that, serum homocysteine level is higher in Parkinson's disease patients than normal healthy individuals. In addition, there was significant positive correlation of elevated serum homocysteine with increased duration of Parkinson's disease and advanced stages of the disease.
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Homocisteína , Enfermedad de Parkinson , Humanos , Homocisteína/sangre , Enfermedad de Parkinson/sangre , Masculino , Femenino , Estudios de Casos y Controles , Persona de Mediana Edad , Anciano , Adulto , Factores de RiesgoRESUMEN
The presence of bright resonance of more than 1 mm or more cusps of the aortic valve, mitral valve or mitral annulus is termed as cardiac valve calcification. If an intense echo producing structure located at the junction of the atrioventricular groove and posterior mitral valve leaflet on Echocardiography that is Mitral annular calcification (MAC). This study was conducted to observe the association of MAC with clinical and echocardiographic findings of ischemic heart disease (IHD) and the role of trans-thoracic echocardiography to detect MAC which is a marker IHD. In this prospective, observational, case-control study, total of 100 IHD patients, 50 patients with MAC were assigned as case group and 50 patients without MAC were control group after fulfilling inclusion criteria. All the detailed history, clinical examination and relevant investigation reports of each patient were recorded in pre designed data collection sheet. MAC was detected with transthorasic echocardiography. Analysis was done to observe the association and correlation of MAC with clinical findings of IHD. Mean age of the case control was 55.16±10.73 years and control was 49.80±8.84 years. MAC was noted highest about 56.0% in between age 45 to 60 years. Eighty two percent (82.0%) of cases and 84.0% of controls were male, 18.0% of cases and 16.0% of controls were female. BMI among the MAC group 2.0% were underweight, 72.0% normal, 24.0% over weight and 2.0% were obese and among non MAC controls group 10.0% were underweight, 68.0% normal, 20.0% over weight and 2.0% were obese. Clinically among cases 14(28.0%) had Stable angina, 8(16.0%) had UA, 3(6.0%) had Non STEMI, 2(4.0%) had AMI, 2(4.0%) had Recent myocardial infarction and 21(42.0%) had OMI. Diabetes mellitus was significantly higher in the case groups (p=0.006). Significant p-value was noted in hyper-triyglyceridemia and low HDL in case group than control. Echocardiographic studies showed 52.0% of cases and 32.0% of controls had regional wall motion abnormality (RWMA). Transthorasic echocardiographically detected MAC is an independent predictor of Ischemic heart disease. The low cost, portable and radiation free nature of the ultrasound approach make MAC an attractive parameter in the ongoing search for IHD.
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Calcinosis , Ecocardiografía , Válvula Mitral , Isquemia Miocárdica , Centros de Atención Terciaria , Humanos , Masculino , Femenino , Persona de Mediana Edad , Isquemia Miocárdica/diagnóstico por imagen , Calcinosis/diagnóstico por imagen , Estudios de Casos y Controles , Ecocardiografía/métodos , Válvula Mitral/diagnóstico por imagen , Válvula Mitral/patología , Estudios Prospectivos , Enfermedades de las Válvulas Cardíacas/diagnóstico por imagen , Enfermedades de las Válvulas Cardíacas/complicaciones , Anciano , AdultoRESUMEN
Dipeptidyl peptidase-4 (DPP-4) inhibitors belong to a prominent group of pharmaceutical agents that are used in the governance of type 2 diabetes mellitus (T2DM). They exert their antidiabetic effects by inhibiting the incretin hormones like glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide which, play a pivotal role in the regulation of blood glucose homoeostasis in our body. DPP-4 inhibitors have emerged as an important class of oral antidiabetic drugs for the treatment of T2DM. Surprisingly, only a few 2D-QSAR studies have been reported on DPP-4 inhibitors. Here, fragment-based QSAR (Laplacian-modified Bayesian modelling and Recursive partitioning (RP) approaches have been utilized on a dataset of 108 DPP-4 inhibitors to achieve a deeper understanding of the association among their molecular structures. The Bayesian analysis demonstrated satisfactory ROC values for the training as well as the test sets. Meanwhile, the RP analysis resulted in decision tree 3 with 2 leaves (Tree 3: 2 leaves). This present study is an effort to get an insight into the pivotal fragments modulating DPP-4 inhibition.
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Teorema de Bayes , Diabetes Mellitus Tipo 2 , Inhibidores de la Dipeptidil-Peptidasa IV , Hipoglucemiantes , Relación Estructura-Actividad Cuantitativa , Inhibidores de la Dipeptidil-Peptidasa IV/química , Inhibidores de la Dipeptidil-Peptidasa IV/farmacología , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/química , Hipoglucemiantes/farmacología , Estructura Molecular , Dipeptidil Peptidasa 4/química , Dipeptidil Peptidasa 4/metabolismo , HumanosRESUMEN
Histone deacetylase 3 (HDAC3), a Zn2+-dependent class I HDACs, contributes to numerous disorders such as neurodegenerative disorders, diabetes, cardiovascular disease, kidney disease and several types of cancers. Therefore, the development of novel and selective HDAC3 inhibitors might be promising to combat such diseases. Here, different classification-based molecular modelling studies such as Bayesian classification, recursive partitioning (RP), SARpy and linear discriminant analysis (LDA) were conducted on a set of HDAC3 inhibitors to pinpoint essential structural requirements contributing to HDAC3 inhibition followed by molecular docking study and molecular dynamics (MD) simulation analyses. The current study revealed the importance of hydroxamate function for Zn2+ chelation as well as hydrogen bonding interaction with Tyr298 residue. The importance of hydroxamate function for higher HDAC3 inhibition was noticed in the case of Bayesian classification, recursive partitioning and SARpy models. Also, the importance of substituted thiazole ring was revealed, whereas the presence of linear alkyl groups with carboxylic acid function, any type of ester function, benzodiazepine moiety and methoxy group in the molecular structure can be detrimental to HDAC3 inhibition. Therefore, this study can aid in the design and discovery of effective novel HDAC3 inhibitors in the future.
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Teorema de Bayes , Inhibidores de Histona Desacetilasas , Histona Desacetilasas , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Relación Estructura-Actividad Cuantitativa , Histona Desacetilasas/química , Histona Desacetilasas/metabolismo , Inhibidores de Histona Desacetilasas/química , Inhibidores de Histona Desacetilasas/farmacología , Análisis Discriminante , Estructura MolecularRESUMEN
Aggregation of the amyloid ß (Aß) peptide into fibrils represents one of the major biochemical pathways underlying the development of Alzheimer's disease (AD). Extensive studies have been carried out to understand the role of fibrillar seeds on the overall kinetics of amyloid aggregation. However, the precise effect of seeds that are structurally or sequentially different from Aß on the structure of the resulting amyloid aggregates is yet to be fully understood. In this work, we use nanoscale infrared spectroscopy to probe the spectral facets of individual aggregates formed by aggregating Aß42 with antiparallel fibrillar seeds of Aß (16-22) and E22Q Aß (1-40) Dutch mutant and demonstrate that Aß can form heterotypic or mixed polymorphs that deviate significantly from its expected parallel cross ß structure. We further show that formation of heterotypic aggregates is not limited to coaggregation of Aß and its isomers, and that the former can form heterotypic fibrils with alpha synuclein and brain protein lysates. These findings highlight the complexity of Aß aggregation in AD and underscore the need to explore how Aß interacts with other brain components, which is crucial for developing better therapeutic strategies for AD.
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BACKGROUND: Apical ground-glass opacification (GGO) identified on CT angiography (CTA) performed for suspected acute stroke was developed in 2020 as a coronavirus-disease-2019 (COVID-19) diagnostic and prognostic biomarker in a retrospective study during the first wave of COVID-19. OBJECTIVE: To prospectively validate whether GGO on CTA performed for suspected acute stroke is a reliable COVID-19 diagnostic and prognostic biomarker and whether it is reliable for COVID-19 vaccinated patients. METHODS: In this prospective, pragmatic, national, multi-center validation study performed at 13 sites, we captured study data consecutively in patients undergoing CTA for suspected acute stroke from January-March 2021. Demographic and clinical features associated with stroke and COVID-19 were incorporated. The primary outcome was the likelihood of reverse-transcriptase-polymerase-chain-reaction swab-test-confirmed COVID-19 using the GGO biomarker. Secondary outcomes investigated were functional status at discharge and survival analyses at 30 and 90 days. Univariate and multivariable statistical analyses were employed. RESULTS: CTAs from 1,111 patients were analyzed, with apical GGO identified in 8.5 % during a period of high COVID-19 prevalence. GGO showed good inter-rater reliability (Fleiss κ = 0.77); and high COVID-19 specificity (93.7 %, 91.8-95.2) and negative predictive value (NPV; 97.8 %, 96.5-98.6). In subgroup analysis of vaccinated patients, GGO remained a good diagnostic biomarker (specificity 93.1 %, 89.8-95.5; NPV 99.7 %, 98.3-100.0). Patients with COVID-19 were more likely to have higher stroke score (NIHSS (mean +/- SD) 6.9 +/- 6.9, COVID-19 negative, 9.7 +/- 9.0, COVID-19 positive; p = 0.01), carotid occlusions (6.2 % negative, 14.9 % positive; p = 0.02), and larger infarcts on presentation CT (ASPECTS 9.4 +/- 1.5, COVID-19 negative, 8.6 +/- 2.4, COVID-19 positive; p = 0.00). After multivariable logistic regression, GGO (odds ratio 15.7, 6.2-40.1), myalgia (8.9, 2.1-38.2) and higher core body temperature (1.9, 1.1-3.2) were independent COVID-19 predictors. GGO was associated with worse functional outcome on discharge and worse survival after univariate analysis. However, after adjustment for factors including stroke severity, GGO was not independently predictive of functional outcome or mortality. CONCLUSION: Apical GGO on CTA performed for patients with suspected acute stroke is a reliable diagnostic biomarker for COVID-19, which in combination with clinical features may be useful in COVID-19 triage.
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COVID-19 , Angiografía por Tomografía Computarizada , Accidente Cerebrovascular , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Biomarcadores , Angiografía por Tomografía Computarizada/métodos , COVID-19/diagnóstico por imagen , Pulmón/diagnóstico por imagen , Pronóstico , Estudios Prospectivos , SARS-CoV-2 , Accidente Cerebrovascular/diagnóstico por imagenRESUMEN
A Disintegrin and Metalloproteinase 17 (ADAM17), a Zn2+-dependent metalloenzyme of the adamalysin family of the metzincin superfamily, is associated with various pathophysiological conditions including rheumatoid arthritis and cancer. However, no specific inhibitors have been marketed yet for ADAM17-related disorders. In this study, 94 quinolinyl methoxyphenyl sulphonyl-based hydroxamates as ADAM17 inhibitors were subjected to classification-based molecular modelling and binding pattern analysis to identify the significant structural attributes contributing to ADAM17 inhibition. The statistically validated classification-based models identified the importance of the P1' substituents such as the quinolinyl methoxyphenyl sulphonyl group of these compounds for occupying the S1' - S3' pocket of the enzyme. The quinolinyl function of these compounds was found to explore stable binding of the P1' substituents at the S1' - S3' pocket whereas the importance of the sulphonyl and the orientation of the P1' moiety also revealed stable binding. Based on the outcomes of the current study, four novel compounds of different classes were designed as promising ADAM17 inhibitors. These findings regarding the crucial structural aspects and binding patterns of ADAM17 inhibitors will aid the design and discovery of novel and effective ADAM17 inhibitors for therapeutic advancements of related diseases.
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Ácidos Hidroxámicos , Relación Estructura-Actividad Cuantitativa , Proteína ADAM17 , Modelos Moleculares , Ácidos Hidroxámicos/químicaRESUMEN
The European Society of Gynaecological Oncology, the European Society for Medical Oncology (ESMO) and the European Society of Pathology held a consensus conference (CC) on ovarian cancer on 15-16 June 2022 in Valencia, Spain. The CC panel included 44 experts in the management of ovarian cancer and pathology, an ESMO scientific advisor and a methodologist. The aim was to discuss new or contentious topics and develop recommendations to improve and harmonise the management of patients with ovarian cancer. Eighteen questions were identified for discussion under four main topics: (i) pathology and molecular biology, (ii) early-stage disease and pelvic mass in pregnancy, (iii) advanced stage (including older/frail patients) and (iv) recurrent disease. The panel was divided into four working groups (WGs) to each address questions relating to one of the four topics outlined above, based on their expertise. Relevant scientific literature was reviewed in advance. Recommendations were developed by the WGs and then presented to the entire panel for further discussion and amendment before voting. This manuscript focuses on the recommendation statements that reached a consensus, their voting results and a summary of evidence supporting each recommendation.
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Oncología Médica , Neoplasias Ováricas , Humanos , Femenino , Sociedades Médicas , España , Neoplasias Ováricas/genética , Neoplasias Ováricas/terapia , Biología MolecularRESUMEN
Magnesium (Mg) has important effects on vascular system and deficiency of this cation is thought to be a risk factor for cerebrovascular atherosclerosis and complications. The study was planned to find out the association of serum magnesium level with severity of neurological disability in patient with acute ischemic stroke. This cross-sectional descriptive study was conducted in the department of Neurology and Medicine at Mymensingh Medical College & Hospital, Mymensingh from June, 2018 to October, 2019. Patients with acute ischemic stroke were evaluated following informed written consent. Diagnosis was confirmed by neuroimaging of brain. Moreover, serum magnesium assay was done for each patient. Data were collected by interview, clinical examination and laboratory investigations of patients using a case record form and analysis was carried out by using the SPSS 22.0 (IBM Inc., Armonk, NY, USA). Mean age of acute ischemic stroke patients was 63.94±13.93 years with male predominance (58.30%). Majority of the respondents (70.2%) had NIH Stroke Scale (NIHSS) score 5-15 (moderate stroke), 13.1% had score 1-5 (minor stroke), 13.1% had score15-20 (Moderate to severe stroke) and 3.6% had score 21-42 (severe stroke). Mean serum magnesium level was 1.83±0.283mg/dl. Hypomagnesaemia was present in 28(33.3%) patients and it was related with higher NIHSS scoring (p<0.05). Multiple regression showed that among the risk factors, serum magnesium level was independently associated with severity of neurological disability of the acute ischemic stroke (p<0.001). In this study, the correlation coefficient between serum magnesium level and NIHSS score was found as r= - 0.667 which showed negative relationship between serum magnesium and NIHSS score. Lower serum magnesium level is associated with the severity of neurological disability of acute ischemic stroke patient. Further case-control studies are required to validate this finding.
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Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Masculino , Persona de Mediana Edad , Anciano , Femenino , Isquemia Encefálica/complicaciones , Magnesio , Estudios TransversalesRESUMEN
BACKGROUND: The study aims to understand system barriers to research participation for people with intellectual disabilities. METHODS: A mixed-methods approach examined the inclusivity of people with intellectual disabilities (IDs) in a random sample of National Institute for Health and Care Research (NIHR) studies conducted in 2019-2020. An online questionnaire (stage 1) was sent to the selected studies lead investigators. An expert by experience panel of 25 people with intellectual disabilities (IDs, stage 2), discussed the stage 1 feedback. Descriptive statistics for quantitative data and thematic analysis for qualitative data was conducted. RESULTS: Of 180 studies reviewed, 131 studies (78%) excluded people with IDs. Of these, 45 (34.3%) study researchers provided feedback. Seven (20%) of the 34 studies which included people with IDs gave feedback. Of all respondents over half felt their study had some relevance to people with IDs. A minority (7.6%) stated their study had no relevance. For a quarter of respondents (23.5%), resource issues were a challenge. Qualitative analysis of both stages produced four overarching themes of Research design and delivery, Informed consent, Resource allocation, and Knowledge and skills. CONCLUSION: Health research continues to exclude people with IDs. Researchers and experts by experience identified non-accessible research design, lack of confidence with capacity and consent processes, limited resources such as time and a need for training as barriers. Ethics committees appear reluctant to include people with cognitive deficits to 'protect' them. People with IDs want to be included in research, not only as participants but also through coproduction.
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Discapacidad Intelectual , Adulto , Humanos , Discapacidad Intelectual/psicología , Inglaterra , Encuestas y CuestionariosRESUMEN
Co2C nanoparticles (NPs) are amongst transition metal carbides whose magnetic properties have not been well explored. An earlier study (Royet al2021J. Phys.: Condens. Matter33375804) showed that a pellet made from Co2C NPs exhibits exchange bias (EB) effect below a temperature,TEB= 50 K and a spin glass (SG) feature emerges belowTSG= 5 K. In the current study we use magnetic, electrical transport, specific heat, and muon spin rotation (µSR) measurements to explore further the magnetic properties of a pellet made with 40 nm diameter pure Co2C NPs. We uncover the onset of Kondo localization at Kondo temperatureTK(= 40.1 K), which is close to the onset temperature (TEB) of the EB effect. A crossover from the Kondo-screened scenario to the Ruderman-Kittel-Kasuya-Yosida interaction-dominated regime is also observed forT
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MMP-2 is potentially contributing to several cancer progressions including leukaemias. Therefore, considering MMP-2 as a promising target, novel anticancer compounds may be designed. Here, 32 in-house arylsulfonyl L-(+) glutamines were subjected to various structure-based computational modelling approaches to recognize crucial structural attributes along with the spatial orientation for higher MMP-2 inhibition. Again, the docking-based 2D-QSAR study revealed that the Coulomb energy conferred by Tyr142 and total interaction energy conferred by Ala84 was crucial for MMP-2 inhibition. Importantly, the docking-dependent CoMFA and CoMSIA study revealed the importance of favourable steric, electrostatic, and hydrophobic substituents at the terminal phenyl ring. The MD simulation study revealed a lower fluctuation in the RMSD, RMSF, and Rg values indicating stable binding interactions of MMP-2 and these molecules. Moreover, the residual hydrogen bond and their interaction analysis disclosed crucial amino acid residues responsible for forming potential hydrogen bonding for higher MMP-2 inhibition. The results can effectively aid in the design and discovery of promising small-molecule drug-like MMP-2 inhibitors with greater anticancer potential in the future.
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Antineoplásicos , Glutamina , Metaloproteinasa 2 de la Matriz , Inhibidores de la Metaloproteinasa de la Matriz , Antineoplásicos/química , Antineoplásicos/farmacología , Simulación por Computador , Glutamina/química , Glutamina/farmacología , Inhibidores de la Metaloproteinasa de la Matriz/química , Inhibidores de la Metaloproteinasa de la Matriz/farmacología , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Relación Estructura-Actividad CuantitativaRESUMEN
Guillain-Barre syndrome (GBS) is an acute autoimmune polyradiculoneuropathy. Neutrophil-lymphocyte ratio (NLR) is a novel prognostic and inflammatory marker in patients with neurological diseases. The study was designed to observe the relation between neutrophil lymphocyte ratio and the clinical severity in patients with Guillain-Barre Syndrome (GBS). This cross-sectional descriptive study was conducted at the department of Neurology and Medicine, Mymensingh Medical College and Hospital from April 2019 to September 2020. Total 58 patients with GBS were enrolled according to the inclusion and exclusion criteria within 7 days of development of symptoms. The clinical diagnosis of GBS was done according to Ausbury and Cornblath's diagnostic criteria; moreover clinical severity was done according to Hughes and Rees scale, Medical Research Council (MRC) grade, cranial nerve involvement and autonomic involvement. After measuring complete blood count, NLR was calculated by dividing neutrophil count to lymphocyte count. Data analysis was done on SPSS 23.0. Mean age of the GBS patients was 36.21±11.55 years. Among 58 respondents 70.69% (41) were male and 29.31% (17) were female. Most of the patients had a GBS severity score of 4(62.07%) followed by 3(27.59%) and 5(10.34%). The mean NLR of the respondents was 3.22±2.25. Acute motor axonal neuropathy (AMAN) was in 48.28% respondents and their mean NLR was 3.89±0.31, 31.03% had AIDP and mean NLR was 3.28±0.46 and 20.69% had Acute motor sensory axonal neuropathy (AMSAN) and mean NLR was 4.5±0.52. The mean NLR of the MRC grade 0, 1, 2, 3 patients was 6.61±1.78, 3.39±0.92, 2.71±1.39 and 1.45±0.40 respectively. Hughes score had a positive correlation (r=0.5333 and p<0.01) and MRC grade had a negative correlation (r= - 0.76805 and p<0.01) with NLR. Severity of GBS was significantly associated with raised NLR. Increase Hughes and Rees scale and decrease MRC grade also related to increased NLR.
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Síndrome de Guillain-Barré , Humanos , Femenino , Masculino , Adulto Joven , Adulto , Persona de Mediana Edad , Síndrome de Guillain-Barré/diagnóstico , Neutrófilos , Estudios Transversales , Linfocitos , HospitalesRESUMEN
Among various matrix metalloproteinases (MMPs), overexpression of MMP9 has been established as a key player in a variety of cancers. Therefore, MMP9 has emerged as a promising biomolecule that may be targeted to design potent inhibitors as novel anticancer therapeutics. In this study, a large database containing 1,123 drug-like MMP-9 inhibitors was considered for robust classification-dependent fragment-based QSAR study through SARpy, Bayesian classification, and recursive partitioning analyses and were validated by both internal and external validation techniques. In a nutshell, all these classification-dependent techniques revealed some common structural alerts and sub-structural fingerprints responsible for modulating MMP-9 inhibition. These observations are in agreement with the interactions obtained from the ligand-bound co-crystal structures of MMP-9 justifying the robustness of the current study. Finally, based on these crucial structural fragments, some new lead compounds were designed and further validated by the binding mode of interaction analysis. Therefore, these findings may be beneficial in designing novel and potential MMP-9 inhibitors in the future as a weapon to combat several cancers.
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Metaloproteinasa 9 de la Matriz , Inhibidores de la Metaloproteinasa de la Matriz , Teorema de Bayes , Metaloproteinasa 9 de la Matriz/metabolismo , Inhibidores de la Metaloproteinasa de la Matriz/química , Inhibidores de la Metaloproteinasa de la Matriz/farmacología , Relación Estructura-Actividad CuantitativaRESUMEN
Hypertrophic cardiomyopathy (HCM) is the most prevalent genetic hereditary cardiomyopathy characterized by sudden cardiac death. Mutations in the MYBPC3 gene are often the most prevalent genetic abnormality in HCM with a prevalence ranging from 20.0 to 42.0%. The mutation spectrum is available for different countries, but such studies are lacking in the Asian population including Bangladeshi patients. A cross-sectional descriptive study was conducted for mutation analysis of the whole MYBPC3 gene on a cohort of 75 HCM Bengali Bangladeshi probands through Next Generation Sequencing at the Genetic Research Lab of Bangabandhu Sheikh Mujib Medical University from 2016 to 2019. The structural and functional impact of the mutations was further analyzed by in silico process. We analyzed the data and found 103 variants in 102 locations in the MYBPC3 gene. Variants were identified in both the coding region and the non-coding region. We found one possibly novel variant in the MYBPC3 gene. The findings of this research will help to develop a genetic database of HCM which will help in the early diagnosis and proper management of HCM patients in Bangladesh. One pathogenic splice donor variant (47356592 C >T) was found in the intronic region. Among the variants in the coding region, one missense mutation was pathogenic (NPâ000247.2: p.Asp770Asn) which was found in seven patients and another one is of conflicting interpretations of pathogenicity (NPâ000247.2: p.Ser217Gly) which was found in two patients. We have identified one in-frame deletion (NPâ000247.2: p.Ala433del) that is possible a novel variant responsible for the development of HCM.
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Cardiomiopatía Hipertrófica , Adulto , Humanos , Cardiomiopatía Hipertrófica/genética , Proteínas Portadoras/genética , Estudios Transversales , MutaciónRESUMEN
INTRODUCTION: Dementia is a global health priority, which requires the healthcare workforce to have the necessary attitudes and skills to deliver person-centred care to people with dementia. Radiographers have frequent contact with people with dementia, and undergraduate training is potentially an optimal time to deliver dementia education. Time for Dementia is an education programme in which undergraduate healthcare students visit a person with dementia and their carer over a two-year period to gain an in-depth understanding of the condition. The aim of this study was to understand undergraduate radiography students' experiences of undertaking the Time for Dementia (TFD) programme. METHODS: Two focus groups were undertaken with 14 radiography students who were half-way through the TFD programme. Data was analysed using thematic analysis. RESULTS: Three key themes were constructed from the analysis: A Holistic Learning Experience, Transferring Learning into Practice and Preparedness & Expectations. Participants discussed the value from learning directly from people with dementia and their carers, reporting an increase in their awareness and understanding of dementia as well as the impact of caring for somebody with the condition. Participants were able to identify learning to take into practice such as person-centred care, compassion, and patience. Challenges to learning were also identified. CONCLUSIONS: This study suggests that a longitudinal, experiential education programme provides radiography students with the opportunity to develop a more holistic understanding of dementia and the impact it may have on the individual and their family members. IMPLICATIONS FOR PRACTICE: Experiential dementia teaching is of value to radiography students, however preparation and learning support should fit with previous personal and teaching experience.
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Atención a la Salud , Demencia , Humanos , Estudiantes , Personal de Salud/educación , Radiografía , Demencia/diagnóstico por imagenRESUMEN
BACKGROUND: Worldwide there are concerns about the supply of nurses into health systems. Understanding and balancing the supply of and demand for healthcare professionals is crucial to efficient healthcare delivery, yet there is relatively little research that examines in detail where nursing students come from and where they go after qualification. OBJECTIVES: To investigate the demographic characteristics of applicants to nursing and midwifery programmes in England, those that are enrolled, attrition during study, and their career intentions on graduation. METHODS: A descriptive case study was conducted in south west England drawing on a complementary set of analyses of routinely collected application and enrolment data from 2017-2020. These were augmented by derivation of student deprivation indices and a follow-up study of nursing and midwifery students qualifying between May 2020 and April 2021. RESULTS: The percentage of males applying for nursing doubled and the mean age of all enrolled students (except midwifery) increased during the study period. The mean level of deprivation of applicants increased from the 51st to the 55th centile indicating widening of participation. Most applying and enrolled students originated from the same region as the nursing school and remained working there on qualification. Successively more males than females were lost from the system at each stage from application to qualification. Qualifying students most common job choice was within acute Trusts, with Medical, District nursing and surgical being the most common choices. The most important factors regarding job choice were location, the characteristics of the Trust, having been there as a student, and family considerations. CONCLUSIONS: The data provide useful information on the nursing educational pipeline. The data discussed here raise questions that would benefit from further regional and national empirical research.
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BACKGROUND: Following a European Society for Medical Oncology Women for Oncology (ESMO W4O) survey in 2016 showing severe under-representation of female oncologists in leadership roles, ESMO launched a series of initiatives to address obstacles to gender equity. A follow-up survey in October 2021 investigated progress achieved. MATERIALS AND METHODS: The W4O questionnaire 2021 expanded on the 2016 survey, with additional questions on the impact of ethnicity, sexual orientation and religion on career development. Results were analysed according to respondent gender and age. RESULTS: The survey sample was larger than in 2016 (n = 1473 versus 482), especially among men. Significantly fewer respondents had managerial or leadership roles than in 2016 (31.8% versus 51.7%). Lack of leadership development for women and unconscious bias were considered more important in 2021 than in 2016. In 2021, more people reported harassment in the workplace than in 2016 (50.3% versus 41.0%). In 2021, ethnicity, sexual orientation and religion were considered to have little or no impact on professional career opportunities, salary setting or related potential pay gap. However, gender had a significant or major impact on career development (25.5% of respondents), especially in respondents ≤40 years of age and women. As in 2016, highest ranked initiatives to foster workplace equity were promotion of work-life balance, development and leadership training and flexible working. Significantly more 2021 respondents (mainly women) supported the need for culture and gender equity education at work than in 2016. CONCLUSIONS: Gender remains a major barrier to career progression in oncology and, although some obstacles may have been reduced since 2016, we are a long way from closing the gender gap. Increased reporting of discrimination and inappropriate behaviour in the workplace is a major, priority concern. The W4O 2021 survey findings provide new evidence and highlight the areas for future ESMO interventions to support equity and diversity in oncology career development.
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Oncología Médica , Condiciones de Trabajo , Humanos , Masculino , Femenino , Factores Sexuales , Encuestas y CuestionariosRESUMEN
BACKGROUND: The Apiaceae or Umbelliferae is one of the largest families in terms of species representation in the plant kingdom. It is also a prominent family in the field of phytochemicals and pharmacology. The family is also quite prominent in the production of spices and condiments and food supplements in nutrition, aside from the potential of species in the family to induce apoptotic, antimicrobial, antitumor, and hepatoprotective activities. OBJECTIVE: This work presents a detailed structural elucidation and functional aspects of phytochemicals from the Apiaceae or Umbelliferae family. METHODS: Furthermore, the application of members of this family in traditional and modern pharmacology is emphasized. This review also highlights the linkage of phytochemicals used in the conventional system of medication for the development of novel therapeutics through a chain of pre-clinical and clinical trials. CONCLUSION: This study may represent a valuable step ahead in the clinical development of natural drugs for curing several ailments, including respiratory and virus-related diseases.