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The value of accurate protein structural models closely conforming to the experimental data is indisputable. DREAMweb deploys an improved DREAM algorithm, DREAMv2, that incorporates a tighter bound in the constraint set of the underlying optimization approach. This reduces the artifacts while modeling the protein structure by solving the distance-geometry problem. DREAMv2 follows a bottom-up strategy of building smaller substructures for regions with a larger concentration of experimental bounds and consolidating them before modeling the rest of the protein structure. This improves secondary structure conformance in the final models consistent with experimental data. The proposed method efficiently models regions with sparse coverage of experimental data by reducing the possibility of artifacts compared to DREAM. To balance performance and accuracy, smaller substructures ( â¼ 200 $\sim 200$ atoms) are solved in this regime, allowing faster builds for the other parts under relaxed conditions. DREAMweb is accessible as an internet resource. The improvements in results are showcased through benchmarks on 10 structures. DREAMv2 can be used in tandem with any NMR-based protein structure determination workflow, including an iterative framework where the NMR assignment for the NOESY spectra is incomplete or ambiguous. DREAMweb is freely available for public use at http://pallab.cds.iisc.ac.in/DREAM/ and downloadable at https://github.com/niladriranjandas/DREAMv2.git.
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Primary growth hormone (GH) resistance or growth hormone insensitivity syndrome, also called Laron syndrome, is a hereditary disease caused by mutations in the GH receptor or in the post-receptor signaling pathway. This disorder is characterized by postnatal growth failure resembling GH deficiency. Differentiating the two conditions is necessary. We present the cases of two siblings, a 16-year-old female and a 9-year-old male, born from a consanguineous union. Both had normal birth weights with subsequent severe short stature and delayed teeth eruption, with no features suggestive of any systemic illness. Serum insulin-like growth factor 1 (IGF1) and insulin-like growth factor binding protein 3 (IGFBP3) were both low. Suspecting GH deficiency, provocative testing with clonidine was done revealing peak growth hormone >40 ng/mL in both patients. In view of low IGF1 and IGFBP3 and high GH on stimulation, IGF1 generation test was done for both siblings, with values supporting the diagnosis of GH insensitivity or Laron syndrome.
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Hormona de Crecimiento Humana , Síndrome de Laron , Masculino , Femenino , Humanos , Adolescente , Niño , Síndrome de Laron/diagnóstico , Hermanos , Hormona del Crecimiento/uso terapéutico , Hormona de Crecimiento Humana/uso terapéutico , Receptores de SomatotropinaRESUMEN
Technology-driven population expansion is closely linked to land use change. Unregulated mining, urbanization, industrialization, and forest clearing threaten land use and cover. This study used GIS and statistical methods to examine land use and cover changes in eastern India's Asansol-Durgapur Development Authority (ADDA). The Kappa coefficient was used to validate each year's LULC map accuracy. This region is changing rapidly due to industrial and urban development, which might cause environmental issues. Thus, this area is ideal for a scientific land-use change study. The central hypothesis of this study is that the LULC of an industrial area is spatially heterogeneous and that the number of hotspots is gradually increasing in response to the dynamicity of land use change over time and space. Three years (1992, 2007, and 2022) were used to determine the estimated transition rate. Hotspots of land use change were identified using autocorrelation statistics for LULC clustering using Moron's I and Gi Z statistics. The proportion of land encompassed by natural vegetation experienced a decline from 12% in 1992 to 4% in 2022. Similarly, the extent of land occupied by agricultural activities decreased from 47 to 38% during the period spanning from 1992 to 2022. The industrial and coal mining sectors experienced a modest growth rate of 1% during the period spanning from 1992 to 2022. If the current rate of land use change persists, it will gradually and consistently alter the existing landscape. This study's findings can potentially inform strategies to mitigate the adverse impacts of industrialization and urbanization on the region's natural resources.
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Minas de Carbón , Conservación de los Recursos Naturales , Conservación de los Recursos Naturales/métodos , Monitoreo del Ambiente/métodos , Bosques , Urbanización , Agricultura , IndiaRESUMEN
Complete gonadal dysgenesis with 46,XY karyotype is a clinical condition characterized by the absence of testicular tissue but with the presence of typical Müllerian structures in a phenotypically female individual. The condition presents as primary amenorrhoea or delayed puberty. Eventually, malignant neoplasms may arise. We report a case of a 16-year-old Indian male with Swyer syndrome presenting with primary amenorrhoea and with an earlier diagnosis of a malignant dysgerminoma in the right ovary.
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Disgerminoma , Disgenesia Gonadal 46 XY , Neoplasias Ováricas , Masculino , Femenino , Humanos , Adolescente , Disgerminoma/diagnóstico , Neoplasias Ováricas/complicaciones , Amenorrea/diagnóstico , Disgenesia Gonadal 46 XY/complicacionesRESUMEN
Economic development fosters a favorable ecosystem for entrepreneurs. Economic development and entrepreneurship ecosystem have positive causality with each other. Subsequently, economic development is also a useful determinant of the entrepreneurship ecosystem and vice-versa. The entrepreneurship ecosystem cannot be nurtured without financial development. However, limited studies have observed the causal association between an entrepreneurship ecosystem and financial inclusion. As financial development has a vital contribution to increasing the entrepreneurship ecosystem, this study examines the cause-and-effect relationship between entrepreneurship ecosystem and financial inclusion across countries. The regression coefficients of selected independent variables are estimated through robust empirical models. For said investigation, the global financial inclusion index and global entrepreneurship ecosystem index score were used as proxy variables for financial inclusion and entrepreneurship ecosystem, respectively in regression analysis. The empirical findings revealed that financial inclusion can be improved with an increase in entrepreneurship ecosystem, economic development, ease of doing business, employers, foreign direct investment net inflow, use of internet facilities, and wage and salaried workers. In the same way, entrepreneurship ecosystem can also be nurtured with financial inclusion, economic development, trade openness, ease of doing business, total employers, use of internet facilities and wage and salaried workers increase. The empirical results also inferred that entrepreneurship ecosystem, gross domestic per capita, foreign direct investment net inflow, ease of doing business, employer's start-up procedures to register a business and wages and salaries are important indicators to expand financial inclusion. Further, the results claimed that entrepreneurship ecosystem and financial inclusion are complementary to each other.
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INTRODUCTION AND OBJECTIVES: It is challenging to adopt a policy of ABO identical platelet transfusion in hemato-oncological patients because of the high demand. Moreover, there are no global standards for the management of ABO non-identical platelet transfusions due to limited evidence. The current study compared the impact of dose and storage duration of platelets on percent platelet recovery (PPR) at 1 h and 24 h between ABO identical and ABO non-identical platelet transfusions in hemato-oncological conditions. The other objectives were to assess the clinical efficacy and compare adverse reactions between the two groups. METHODS: A total of 130 random donor platelet transfusion episodes (81 ABO identical and 49 ABO non-identical) were evaluated in 60 eligible patients with different malignant, as well as non-malignant, hematological conditions. All analysis was performed using two-sided tests, and p-values <0.05 were considered significant. RESULTS: The PPR at 1 h and 24 h was significantly higher in ABO identical platelet transfusion. Platelet recovery and survival were not affected by the gender, dose or storage duration of platelet concentrate. Aplastic anemia and myelodysplastic syndrome (MDS) disease conditions were observed to be independent risk predictors for 1-h post-transfusion refractoriness. CONCLUSION: ABO identical platelets have higher platelet recovery and survival. Both ABO identical and ABO non-identical platelet transfusions have similar efficacy in controlling bleeding episodes up to World Health Organization (WHO) grade two. Assessment of other factors, such as platelet functional properties in the donor, anti-HLA and anti-HPA antibodies, may be needed to better understand the platelet efficacy of platelet transfusions.
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Nuclear magnetic resonance (NMR) spectroscopy can reveal conformational states of a protein in physiological conditions. However, sparsely available NMR data for a protein with large degrees of freedom can introduce structural artifacts in the built models. Currently used state-of-the-art methods deriving protein structure and conformation from NMR deploy molecular dynamics (MD) coupled with simulated annealing for building models. We provide an alternate graph-based modeling approach, where we first build substructures from NMR-derived distance-geometry constraints combined in one shot to form the core structure. The remaining molecule with inadequate data is modeled using a hybrid approach respecting the observed distance-geometry constraints. One-shot structure building is rarely undertaken for large and sparse data systems, but our data-driven bottom-up approach makes this uniquely feasible by suitable partitioning of the problem. A detailed comparison of select models with state-of-art methods reveals differences in the secondary structure regions wherein the correctness of our models is confirmed by NMR data. Benchmarking of 106 protein-folds covering 38-282 length structures shows minimal experimental-constraint violations while conforming to other structure quality parameters such as the proper folding, steric clash, and torsion angle violation based on Ramachandran plot criteria. Comparative MD studies using select protein models from a state-of-art method and ours under identical experimental parameters reveal distinct conformational dynamics that could be attributed to protein structure-function. Our work is thus useful in building enhanced NMR-evidence-based models that encapsulate the contextual secondary and tertiary structure variations present during the experimentation and expand the scope of functional inference.
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Proteínas , Conformación Proteica , Modelos Moleculares , Proteínas/química , Espectroscopía de Resonancia Magnética/métodos , Estructura Secundaria de ProteínaRESUMEN
Poverty is not only the focal issue that has drawn worldwide attention but is also an essential issue in people's livelihoods. This research examines the primary factors of poverty in the Birbhum district. Multivariate statistical techniques have been used to identify the primary determinants. Ten parameters have been identified as significant drivers of poverty, six of which are physical, viz. slope, elevation, drainage density, pond frequency, soil texture, and rainfall. The remaining four sociocultural and economic parameters are literacy, major market center, population growth, and road density. A linear relationship has been established between the explanatory and response variables where the R-square or coefficient of determination value is 0.741, and this relationship explains more than 74% of the variables. The P-value of multi-linear regression is 0.000, which validates the model and permits the data for factor analysis to extract the major determinants. Factor analysis indicates that five essential factors have been found based on their eigenvalue viz., agro-climatic factor, infrastructural and educational factors, hydrological factor, demographic factor, and pedological factors. All the p-values of the correlation matrix are < 0.05, meaning all the relationships are valid and significant. This research also demonstrates the spatial analysis of data using GIS technology. The western part of the study area has been affected by the high influence of all factors due to the presence of plateau fringe and associated low productivity. The outcomes of the research are scientifically significant and this study helps the planners, higher authorities, and social workers to eradicate poverty from this region through formulating better policies and management.
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Graves' dermopathy is one of the extra-thyroidal manifestations of Graves' disease (GD) and is characterized by the accumulation of glycosaminoglycans in the reticular dermis. In the majority of cases, pretibial myxedema is self-limiting but, in some cases, it can lead to structural and functional damage. Topical steroids with occlusive dressing remain the conventional treatment, but intralesional steroids have shown promising results. We hereby present a case of pretibial myxedema treated successfully with intralesional triamcinolone acetate.
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Objective ABO typing constitutes cell grouping and serum grouping. The discrepancy may arise in ABO typing due to a mismatch in cell grouping and serum grouping. It may be due to technical errors, missing or weak ABO antibodies (type I), weak ABO subgroups (type II), Rouleaux formation (type III), or other miscellaneous reasons (type IV). This study was carried out to determine the prevalence and cause of ABO blood group discrepancy in donor samples at our center. Methods A retrospective study of ABO blood group typing of blood donors was conducted at our center. The blood group typing was routinely performed using gel cards and a microcentrifuge system (Tulip Diagnostics(P) Ltd, Goa, India). If any discrepancy in ABO typing was noted, the test was repeated using the conventional tube technique. After sorting clerical/technical error, the causes of discrepancy were analyzed and resolved using anti-A 1 , anti-H, anti-AB, and other immunohematological tests like antibody screening and identification, saliva inhibition test, adsorption-elution studies. Results A total of 12,715 (98.6% males and 1.4% females) donor samples were tested. The number of ABO discrepancies detected were 15 (0.12%). The discrepancies were characterized as type I (6 cases; 40%), type II (1 case; 6.7%), type III (0 cases; 0%), and type IV (8 cases; 53.3%). Three cases, each of anti-M and anti-Le b , were detected in the study population. A single case of A 3 , a subgroup of A blood group, was found during the study. Conclusion The prevalence of ABO group discrepancy was 0.12% at our center. Discrepancy arising during ABO typing of blood donor must be resolved before reporting ABO blood group to minimize the recipient's chances of transfusion reaction. The serum grouping is equally crucial as cell grouping for reporting the ABO group of an individual.
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Juvenile granulosa cell tumor leading to isosexual peripheral precocious puberty is a well-known association. Here, we report a rare case of central precocious puberty secondary to granulosa cell tumor of the ovary. A five-year and five-month-old girl presented with a history of progressive enlargement of bilateral breasts and intermittent vaginal spotting, associated with growth acceleration. Elevated estradiol and suppressed serum follicle-stimulating hormone were found on investigation. Additionally, abdominal and pelvic ultrasonography was suggestive of a right ovarian mass, which proved to be a juvenile granulosa cell tumor on histopathology and immunohistochemistry, leading to a diagnosis of peripheral precocious puberty secondary to granulosa cell tumor of the ovary. One and a half years after resection of the tumor, secondary sexual characteristics progressed with regression of tumor markers, and no mass was noted on ultrasonography, leading to the suspicion of central precocious puberty. Pubertal basal luteinizing hormone (LH) and elevated triptorelin-stimulated LH confirmed the diagnosis of central precocious puberty secondary to granulosa cell tumor of the ovary.
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A male patient aged 11 years diagnosed with acute myeloid leukemia presented with complaints of fever, lethargy, and bleeding manifestations. On ordering red blood cells and platelet transfusion, his blood group was tested. Blood group discrepancy was observed in that forward grouping showed the O Rh D positive blood group and reverse grouping revealed the A Rh D positive. The patient's previous blood group record was O Rh D positive, and he had a transfusion history of O Rh D positive red blood cells and platelets in other hospital. Initial immunohematological workup results, including adsorption and heat elution, were consistent with the O Rh D-positive blood group, but further workups on follow-up after the commencement of chemotherapy showed that his original blood group was A Rh D positive, in which the A antigen expression was previously masked by the underlying disease condition of the patient. Hence, the correlation of laboratory results with clinical details and case history is an essential step in resolving such blood group discrepancies.
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Leucemia Mieloide Aguda , Sistema del Grupo Sanguíneo ABO , Tipificación y Pruebas Cruzadas Sanguíneas , Niño , Eritrocitos , Hospitales , Humanos , Leucemia Mieloide Aguda/tratamiento farmacológico , MasculinoRESUMEN
The diffusion of COVID-19 or Coronavirus since last few months is the prime matter of concern for the entire world. The government of India had declared the complete lockdown from 24th March. After the second step lockdown, now third step lockdown was declared. So, India in Lockdown 3.0 situation. Although the economy of our country has severely been affected by the impact of lockdown, this situation is good for natural healing. Major metropolitan cities of India are trying to recover from various pollution. This study, therefore, attempts to analyze the trend of air pollution before and during a lockdown situation in Kolkata metropolitan and surrounding areas. To identify air pollution trends before and during the lockdown, the non-parametric Maan-Kendall test and Sen's slope estimator have been applied in this study. This research has been done based on air quality index data of the Kolkata metropolitan region's observatory stations. The time range of the data set is from mid of February to 2nd May. The study results show that air pollution has been reduced up to 80% in almost all the stations due to strict lockdown.
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BACKGROUND AND OBJECTIVES: The United States is experiencing an epidemic of opioid-related deaths. Naloxone, the drug of choice for reversing acute opioid overdose, is not routinely prescribed for outpatient use. The aims of this project were to improve naloxone awareness, increase naloxone prescribing, and prevent opioid overdoses. METHODS: A naloxone counseling intervention was implemented in three family health centers by an interprofessional team of providers including family medicine physicians, clinical pharmacists, and social workers. An outreach letter was designed with provider input, an electronic order set was developed to facilitate prescribing, and intranasal naloxone kits were assembled for free dispensing. Providers and staff received education about opioid overdose and naloxone prescribing. Faculty and resident physicians were surveyed before and after the intervention to assess their attitudes. Patients who received naloxone kits were surveyed to assess their attitudes and use of opioids and naloxone. RESULTS: Over 16 months, 71 outreach letters were distributed and 97 naloxone kits were dispensed. The majority of kits were prescribed for illicit opioid use. Faculty and resident physician surveys indicated improved knowledge about naloxone prescribing, and increased professional satisfaction caring for patients requesting opioids. Surveyed patients endorsed high levels of comfort discussing opioid use with their primary care physician. Five successful opioid overdose reversals were reported. CONCLUSIONS: An interprofessional naloxone counseling intervention engaged patients in opioid use discussions, increased provider satisfaction, and reversed overdoses. Improving naloxone access is an essential component of comprehensive overdose prevention programs that encourage responsible opioid prescribing and use.
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Analgésicos Opioides/uso terapéutico , Consejo/métodos , Reducción del Daño , Conocimientos, Actitudes y Práctica en Salud , Naloxona/administración & dosificación , Antagonistas de Narcóticos/administración & dosificación , Participación del Paciente , Analgésicos Opioides/efectos adversos , Sobredosis de Droga/prevención & control , Humanos , Grupo de Atención al Paciente , Médicos de Atención Primaria , Pautas de la Práctica en Medicina/tendencias , Estados UnidosRESUMEN
Clindamycin hydrochloride (CLH) is a clinically important oral antibiotic with wide spectrum of antimicrobial activity that includes gram-positive aerobes (staphylococci, streptococci etc.), most anaerobic bacteria, Chlamydia and certain protozoa. The current study was focused to develop a stabilised clindamycin encapsulated poly lactic acid (PLA)/poly (D,L-lactide-co-glycolide) (PLGA) nano-formulation with better drug bioavailability at molecular level. Various nanoparticle (NPs) formulations of PLA and PLGA loaded with CLH were prepared by solvent evaporation method varying drug: polymer concentration (1:20, 1:10 and 1:5) and characterised (size, encapsulation efficiency, drug loading, scanning electron microscope, differential scanning calorimetry [DSC] and Fourier transform infrared [FTIR] studies). The ratio 1:10 was found to be optimal for a monodispersed and stable nano formulation for both the polymers. NP formulations demonstrated a significant controlled release profile extended up to 144 h (both CLH-PLA and CLH-PLGA). The thermal behaviour (DSC) studies confirmed the molecular dispersion of the drug within the system. The FTIR studies revealed the intactness as well as unaltered structure of drug. The CLH-PLA NPs showed enhanced antimicrobial activity against two pathogenic bacteria Streptococcus faecalis and Bacillus cereus. The results notably suggest that encapsulation of CLH into PLA/PLGA significantly increases the bioavailability of the drug and due to this enhanced drug activity; it can be widely applied for number of therapies.
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Fenómenos Fisiológicos Bacterianos/efectos de los fármacos , Clindamicina/administración & dosificación , Clindamicina/química , Preparaciones de Acción Retardada/administración & dosificación , Ácido Láctico/química , Nanocápsulas/química , Ácido Poliglicólico/química , Administración Oral , Antibacterianos/administración & dosificación , Antibacterianos/química , Supervivencia Celular/efectos de los fármacos , Preparaciones de Acción Retardada/síntesis química , Difusión , Sinergismo Farmacológico , Copolímero de Ácido Poliláctico-Ácido PoliglicólicoRESUMEN
There's a better way to clear secretions from a neonate's mouth and nose, and it's less likely to cause adverse effects.
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Atención Perinatal/métodos , Frecuencia Respiratoria/fisiología , Succión/métodos , Femenino , Humanos , MasculinoRESUMEN
Effect of chlorpyrifos pesticide on testicular oxidative damage was studied in Sprague-Dawley rats at varying doses. At lower doses (5 and 10 mg/kg body weight/30 days), reduction in plasma levels of testosterone and follicular stimulating hormone (FSH) and luteinizing hormone (LH) along with significant shrinkage of seminiferous tubules and drastic changes in germ cells were seen. But these adverse changes of testes were restored with the revival of serum testosterone and FSH and LH at higher doses (20 and 30 mg/kg body weight/30 days). Similarly, levels of testicular lipid peroxidation and diene conjugates were elevated whereas activities of antioxidant enzymes (superoxide dismutase, catalase and glutathione peroxidase), steroidogenic (Δ(5), 3ß-HSD and Δ(5), 17ß-HSD) enzymes and angiotensinogen-converting enzyme and glutathione content including lipid-protein content of testes were decreased at low doses. But at higher doses, reductions in level of lipid peroxidation (as revealed by malondialdehyde [MDA] value) and conjugated dienes were found and on the contrary, revivals of testicular antiperoxidative/antioxidant enzymes defense systems, angiotensinogen-converting enzyme (ACE), steroidogenic enzymes, lipid-protein and antioxidant glutathione content were observed. Therefore, the present study indicated from the results that chlorpyrifos had a dual effect at both doses on oxidative stress changes, but at higher doses, the cells were triggering its natural defense mechanism to combat the insult of lower doses of chlorpyrifos and became operative possibly through corrective measure of antioxidant enzymes defense system and pituitary gonadotropins hormones feedback mechanisms on testes.
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Cloropirifos/toxicidad , Insecticidas/toxicidad , Estrés Oxidativo , Testículo/efectos de los fármacos , Animales , Hormona Folículo Estimulante/sangre , Peroxidación de Lípido , Hormona Luteinizante/sangre , Masculino , Malondialdehído/metabolismo , Oxidorreductasas/metabolismo , Ratas , Ratas Sprague-Dawley , Espermatogénesis/efectos de los fármacos , Testículo/metabolismo , Testículo/patología , Testosterona/sangreRESUMEN
The present study examined the adverse effects of delta-9-tetrahydrocannabinol (i.p injection in albino mice) on free radical damage of testicular lipids (lipid peroxidation) at low doses and the role of antioxidant enzymes defense system at high dose and particularly at the withdrawal of the drug after applying higher dose (recovery dose). At lower doses (total doses ranging from 6 mg to 28 mg), there was a significant increase of lipid peroxidation and decrease in testicular lipid content. But the effects were slightly lowered at high dose (total dose 70 mg) and at the withdrawal of the drug (recovery dose). Similarly, marked decrease of antioxidant enzyme systems (superoxide dismutase, catalase, and glutathione peroxidase) and glutathione content were noticed at low doses. But the effects were slightly higher at high dose and at the withdrawal of the drug. Similarly, low-dose treatments caused significant shrinkage of tubular diameter and detrimental changes in seminiferous epithelium of testis resulting in lowered plasma testosterone and pituitary gonadotropins (follicular stimulating and luteinizing hormone levels. But at high dose and particularly at withdrawal of the drug, regression of seminiferous tubules and recovery of various germ cell layers of testes through the revival of testosterone hormone and pituitary gonadotropins were observed.