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Background & objectives: Investment in mental health is quite meagre worldwide, including in India. The costs of new interventions must be clarified to ensure the appropriate utilization of available resources. The government of Gujarat implemented QualityRights intervention at six public mental health hospitals. This study was aimed to project the costs of scaling up of the Gujarat QualityRights intervention to understand the additional resources needed for a broader implementation. Methods: Economic costs of the QualityRights intervention were calculated using an ingredients-based approach from the health systems' perspective. Major activities within the QualityRights intervention included assessment visits, meetings, training of trainers, provision of peer support and onsite training. Results: Total costs of implementing the QualityRights intervention varied from Indian Rupees (â¹) 0.59 million to â¹ 2.59 million [1United States Dollars (US $) = â¹ 74.132] across six intervention sites at 2020 prices with 69-79 per cent of the cost being time cost. Scaling up the intervention to the entire State of Gujarat would require about two per cent increase in financial investment, or about 7.5 per cent increase in total cost including time costs over and above the costs of usual care for people with mental health conditions in public health facilities across the State. Interpretation & conclusions: The findings of this study suggest that human resources were the major cost contributor of the programme. Given the shortage of trained human resources in the mental health sector, appropriate planning during the scale-up phase of the QualityRights intervention is required to ensure all staff members receive the required training, and the treatment is not compromised during this training phase. As only about two per cent increase in financial cost can improve the quality of mental healthcare significantly, the State government can plan for its scale-up across the State.
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Atenção à Saúde , Hospitais Públicos , Humanos , Aconselhamento , Saúde Mental , Índia/epidemiologiaRESUMO
BACKGROUND: Pathological effects of dysglycemia and insulin resistance on atherosclerosis and cardiac remodeling starts as early as in the prediabetic state before the onset of overt diabetes. Activin A is a molecule with multiple functions, including an important part in glucose homeostatic mechanisms as well as inflammatory processes and is therefore being researched as a useful novel biomarker for prompt recognition of the risk of cardiovascular disease (CVD) in prediabetic individuals, thereby helping in disease prognostication and early institution of therapeutic measuresObjective: The study aimed to measure serum levels of activin A in prediabetic patients and evaluate them in comparison to normoglycemic controls. The association of activin A with carotid intima media thickness (CIMT), left ventricular diastolic dysfunction (LVDD), and homeostatic assessment of insulin resistance (HOMA-IR) was also studiedMaterials and methods: A total of 60 prediabetic cases and 60 normoglycemic control subjects [matched as per age, gender, and body mass index (BMI)] were recruited. Measurement of serum glucose levels (fasting and postprandial) and fasting insulin levels and glycated hemoglobin (HbA1c) levels were done in all the subjects. The values of HOMA-IR were computed using established formulae. Enzyme-linked immunosorbent assay (ELISA) kits were used for the evaluation of serum levels of activin A in both groups. Parameters for the two groups were compared. In the cases, CIMT (using B-mode ultrasound) and LVDD (using two-dimensional (2D) echocardiography) were measured and correlated with activin A levelsResults: Serum fasting insulin (mIU/L) was considerably higher in cases than in the controls (p < 0.001). HOMA-IR median [interquartile range (IQR)] was 4 (3.25-4.93) in some cases, and that in the control group was 1.2 (0.88-1.5) (p < 0.001). Serum activin A levels in the cases group had a median (IQR) of 263.55 (227.1-279.5) ng/mL, which was substantially greater as compared to the control group 159.9 (150.7-178.7) ng/mL (p < 0.001). A significant positive association of serum activin A levels with HOMA-IR (ρ = 0.75, p < 0.001) and CIMT (ρ = 0.50, p < 0.001) was found. In LVDD grade I and II groups, the serum levels of activin A were 257.86 (219.3-271.2) ng/mL and 269 (244.19-291.5) ng/mL, respectively (p = 0.12)Conclusion: A substantial proportion of morbidity and mortality related to dysglycemic states can be attributed to cardiovascular complications. Elevated levels of activin A in prediabetes can act as an indicator of subclinical CVD leading to early diagnosis and intervention.
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Aterosclerose , Doenças Cardiovasculares , Resistência à Insulina , Insulinas , Estado Pré-Diabético , Humanos , Espessura Intima-Media Carotídea , Doenças Cardiovasculares/complicações , Glucose , Fatores de Risco , Glicemia/análise , InsulinaRESUMO
BACKGROUND: Recognising the significant extent of poor-quality care and human rights issues in mental health, the World Health Organization launched the QualityRights initiative in 2013 as a practical tool for implementing human rights standards including the United Nations Convention on Rights of Persons with Disabilities (CRPD) at the ground level. AIMS: To describe the first large-scale implementation and evaluation of QualityRights as a scalable human rights-based approach in public mental health services in Gujarat, India. METHOD: This is a pragmatic trial involving implementation of QualityRights at six public mental health services chosen by the Government of Gujarat. For comparison, we identified three other public mental health services in Gujarat that did not receive the QualityRights intervention. RESULTS: Over a 12-month period, the quality of services provided by those services receiving the QualityRights intervention improved significantly. Staff in these services showed substantially improved attitudes towards service users (effect sizes 0.50-0.17), and service users reported feeling significantly more empowered (effect size 0.07) and satisfied with the services offered (effect size 0.09). Caregivers at the intervention services also reported a moderately reduced burden of care (effect size 0.15). CONCLUSIONS: To date, some countries are hesitant to reforming mental health services in line with the CRPD, which is partially attributable to a lack of knowledge and understanding about how this can be achieved. This evaluation shows that QualityRights can be effectively implemented even in resource-constrained settings and has a significant impact on the quality of mental health services.
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BACKGROUND: Atherosclerotic cardiovascular diseases are the leading cause of morbidity and mortality in both diabetics and prediabetics. In insulin resistant states, increased levels of various adipose derived cytokine (adipokine) have been found to have an important role in the process of atherosclerosis. One such novel adipokine is RBP4, (belonging to lipokalin family) which also by exerting an inflammatory process has a role in the pathogenesis of insulin resistance and CVD.. Early detection of all these inflammatory cytokines may immensely help us in prognosticating the pace of disease besides instituting early interventional manuevers. OBJECTIVE: The aim of the study was to compare serum levels of RBP4 in prediabetics and controls and to correlate levels of RBP4 with HOMA-IR and CIMT. METHODS: 60 prediabetic patients and 60 age, sex, BMI matched controls were employed in the case control study. In both cases and controls serum levels of fasting and postprandial blood glucose, glycated hemoglobin (HbA1c) and fasting insulin levels were measured. HOMA-IR values in both the groups were calculated using fasting glucose and insulin levels. Serum RBP4 levels were measured using ELISA. The values obtained were compared between cases and controls. CIMT was only measured in cases using B-mode ultrasonography. RESULTS: Median (IQR) of fasting plasma insulin levels (uIU/ml)in cases was 11.3 (10.175-13.505) versus that of controls which was 5.73 (4.3-7.1). HOMA-IR median (IQR) in cases and controls was 3.12 (2.73-3.595) and 1.21(0.918-1.505) respectively. Median (IQR) for RBP4 in cases was 67.4 (46.166-111.088) which was significantly higher as compared to controls 33.92 (23.902-52.45). Significant positive correlation was seen between RBP4 with both, HOMA-IR and mean CIMT with correlation coefficients of 0.3693 and 0.621 respectively. On performing univariate linear regression analysis it was found that with increase in serum RBP4 levels by 1 mg/L, HOMA-IR and mean CIMT significantly increased by 0.007 units and 0.001 mm respectively. METHODS: 60 prediabetic patients and 60 age, sex, BMI matched controls were employed in the case control study. In both cases and controls serum levels of fasting and postprandial blood glucose, glycated hemoglobin (HbA1c) and fasting insulin levels were measured. HOMA-IR values in both the groups were calculated using fasting glucose and insulin levels. Serum RBP4 levels were measured using ELISA. The values obtained were compared between cases and controls. CIMT was only measured in cases using B-mode ultrasonography. CONCLUSION: Prediabetics have been found to have more risk of cardiovascular events as compared to normoglycemics. Early assessment of the same with the use of novel biomarkers like RBP4 can be considered for early detection of atherosclerosis in prediabetic individuals. It may further help in early intervention and thus prevention from future complications.
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Aterosclerose , Resistência à Insulina , Estado Pré-Diabético , Biomarcadores , Estudos de Casos e Controles , Humanos , Estado Pré-Diabético/diagnóstico , Proteínas Plasmáticas de Ligação ao RetinolRESUMO
OBJECTIVE: The aim of the study was to compare serum levels of Transthyretin in prediabetics and controls and to correlate levels of same with HOMA-IR and mean CIMT Method: It was a case control study in which 60 prediabetic patients and 60 controls (age, sex, BMI matched) were employed. Plasma levels of glucose (fasting and postprandial), glycated hemoglobin (HbA1c), and serum levels of insulin (fasting) were measured in both cases and controls. HOMA-IR values in both the groups were calculated using fasting plasma glucose and serum insulin levels. Serum Transthyretin levels were measured using ELISA. The values obtained were compared between cases and controls. In cases, obtained serum levels of Transthyretin were correlated with HOMA-IR values and mean CIMT (measured in cases only using B-mode ultrasonography). RESULTS: Median (IQR) of serum levels of insulin (fasting in µIU/ml) in cases {11.3 (10.175-13.505)} was significantly higher than that of controls {5.73 (4.3-7.1)}. HOMA-IR median (IQR) in cases and controls was 3.12 (2.73-3.595) and 1.21(0.918- 1.505) respectively. Median (IQR) for serum levels of Transthyretin was also significantly higher in cases as compared to controls [46.74 (30.43-81.225) and 22.38 (16.628-27.89) respectively]. Significant positive correlations were observed between serum levels of Transthyretin with both HOMA-IR and mean CIMT (with correlation coefficients being 0.288 and 0.536 respectively). Univariate linear regression analysis showed that with increase in serum Transthyretin by 1 mg/ dl, mean CIMT increases by 0.001 mm. CONCLUSION: Individuals with impaired glucose tolerance have been found to have increased risk of atherosclerosis as compared to normoglycemics after excluding other risk factors. Assessment for the risk of same with the help of novel markers can help in diagnosis and intervention at an early stage and thereby preventing risk of further complications.
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Aterosclerose , Resistência à Insulina , Pré-Albumina , Estado Pré-Diabético , Aterosclerose/diagnóstico , Aterosclerose/epidemiologia , Biomarcadores , Glicemia , Estudos de Casos e Controles , Humanos , Insulina , Pré-Albumina/genética , Pré-Albumina/metabolismoRESUMO
Herein, a prolinamide-derived peptidomimetic that preferentially binds to c-MYC and BCL2 G-quadruplexes present in the promoter regions of apoptosis-related genes (c-MYC and BCL2) over other DNA quadruplexes are described. Biological assays, such as real-time quantitative reverse transcription, western blot, dual luciferase, and small interfering RNA knockdown assays, indicate that the ligand triggers a synthetic lethal interaction by simultaneously inhibiting the expression of c-MYC and BCL2 genes through their promoter G-quadruplexes. The ligand shows antiproliferative activity in MCF-7 cells that overexpress both MYC and BCL2 genes, in comparison to cells that overexpress either of the two. Moreover, the ligand induces S-phase cell-cycle arrest, DNA damage, and apoptosis in MCF-7 cells.
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Antineoplásicos/farmacologia , Regulação para Baixo/efeitos dos fármacos , Quadruplex G , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , Bibliotecas de Moléculas Pequenas/química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Feminino , Humanos , Ligantes , Prolina/análogos & derivados , Prolina/química , Regiões Promotoras Genéticas , Proteínas Proto-Oncogênicas c-bcl-2/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-myc/antagonistas & inibidores , Pontos de Checagem da Fase S do Ciclo Celular/efeitos dos fármacos , Mutações Sintéticas LetaisRESUMO
BACKGROUND: The pathophysiological effects of diabetes on the heart and the rest of the cardiovascular system begins much earlier in its precedent stage of prediabetes and one major underlying defect is insulin resistance. Heart-type fatty acid binding protein (H-FABP) is a recently studied molecule inherent to the cardiac myocytes found to rise in both coronary and non-coronary heart diseases. The utility of the molecule in prediabetes and its relationship with insulin resistance is being studied. OBJECTIVE: The aim of the study is to compare serum levels of H-FABP in prediabetics and controls and correlate them with Homeostatic model assessment - insulin resistance (HOMA-IR). METHODS: 50 prediabetic patients and 50 age, sex and BMI matched controls were employed in the case control study. Serum fasting and postprandial blood sugars, glycosylated hemoglobin (HbA1c), fasting insulin levels were measured in cases and controls. HOMA-IR index was calculated from fasting glucose and insulin values. Serum H-FABP was measured in both cases and controls using Immunoturbidimetric method with anti- H-FABP coated latex reagent kits. The values were compared between both the groups. RESULTS: The mean serum fasting insulin level among cases was 12.22mIU/ml and that of the control group was 5.37mIU/ml (p value <0.0001). HOMA- IR mean values were 3.31 ± 1.56 and 1.16 ± 0.44 in cases and controls respectively (p- <0.001). The mean serum levels of H-FABP among cases and controls were 6.38± 2.76ng/ml and 3.24 ± 2.47 ng/ml respectively (p <0.0001). The correlation between the two variables, HOMA-IR and H-FABP was also found to be strongly positive (r=0.675). Linear regression analysis showed that for 1 unit increase in HOMA-IR, H-FABP increased by 1.095 and for 1 unit increase in Fasting insulin, H-FABP increased by 0.038. CONCLUSION: Prediabetics have a higher risk of cardiovascular morbidity when compared to normoglycemics with insulin resistance being the single most important contributor. Serum H-FABP levels are elevated in prediabetes representing a marker of subclinical cardiovascular disease (CVD).
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Biomarcadores/metabolismo , Sistema Cardiovascular , Resistência à Insulina , Estado Pré-Diabético/sangue , Glicemia , Estudos de Casos e Controles , Proteína 3 Ligante de Ácido Graxo/sangue , Proteínas de Ligação a Ácido Graxo/sangue , Humanos , InsulinaRESUMO
OBJECTIVE: To assess the association of oxidative stress and serum vitamin D levels in sensory neuropathy in prediabetes. METHODS: Serum and urine levels of 8-OHdG (a marker of oxidative stress) and serum levels of vitamin D were compared in prediabetic patient having sensory neuropathy to those who did not have sensory neuropathy as determined by VPTs measured by Digital Biothesiometer and MNSI (Michigan Neuropathy Screening Instrument). RESULT: A total of 60 prediabetic cases between 35 years to 60 years were included in this study. Among all the prediabetic subjects, 43.3 % subjects had neuropathy according to VPTs measured by Biothesiometer. T-test analysis suggested that serum levels of 8-OHdG were significantly higher in subjects with neuropathy than subjects without neuropathy (1006.58 ± 511.8 vs 688.6 ± 607.3, p value = 0.035). Urinary levels of 8-OHdG were also significantly higher in subjects with neuropathy than subjects without neuropathy (699.35 ± 419.5 vs 474.57 ± 402.5, p-value = 0.04). No such significant difference however was present in serum levels of vitamin D between neuropathic and non-neuropathic prediabetics (20.13 ± 18.44 vs 16.96 ± 11.72, p value = 0.419. VPTs were found to have statistically significant positive correlation with serum 8-OHdG {, Pearson Correlation Coefficient= 0.317(R), 0.307(L); p-value=0.014(R),0.017(L)} and urine 8-OHdG levels{Pearson Correlation Coefficient= 0.288(R), 0.255(L); p-value=0.026(R), 0.049(L),}. According to MNSI physical assessment score (> or = 2), 38.3 % subjects (23 subjects) had neuropathy. MNSI score is positively correlated with serum 8-OHdG (Pearson Correlation Coefficient = 0.308; p-value = 0.017). Correlation with urine 8-OHdG was not statistically significant (Pearson Correlation Coefficient= 0.687; p value = 0.06). Correlations of MNSI scores {Pearson Correlation Coefficient=0.14, p-value=0.287} and VPTs{Pearson Correlation Coefficient= 0.058(R), 0.189(L); p-value=0.660(R), 0.148(L)} with serum vitamin D levels were not statistically significant. CONCLUSION: Oxidative stress, as confirmed by the biomarker, 8-OHdG, has a important role in the development of this sensory neuropathy.
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Doenças do Sistema Nervoso Periférico , Estado Pré-Diabético , Nefropatias Diabéticas , Humanos , Estresse Oxidativo , Vitamina D , VitaminasRESUMO
Unplanned urbanization and secondary migration has caused increased spurt in arboviral diseases especially Dengue and Chikungunya. With this exponential rise in these illness, now we are beginning to notice uncommon presentations of these common illnesses. Here we present two interesting cases: one of paraparesis and another of quadriparesis with respiratory involvement secondary to Chikungunya, although the mechanism in one is hypokalemia and the other is GBS secondary to Chikungunya. Just the magnitude of cases presenting in metros and major cities of our country warrant sensitizing the physicians about these uncommon manifestations..
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Febre de Chikungunya/diagnóstico , Febre de Chikungunya/complicações , Febre de Chikungunya/patologia , Dengue , Vírus da Dengue , Humanos , Hipopotassemia/complicações , Hipopotassemia/diagnóstico , Quadriplegia/complicações , Quadriplegia/diagnósticoRESUMO
Herein we report the design, synthesis, biophysical and biological evaluation of triazole containing prolinamide derivatives as selective c-MYC G-quadruplex binding ligands. A modular synthetic route has been devised for prolinamide derivatives using a copper(i) catalyzed azide-alkyne cycloaddition (CuAAC). The Förster resonance energy transfer (FRET) melting assay indicates that prolinamide trimers can significantly stabilize G-quadruplex structures over duplex DNA compared to prolinamide dimers. The fluorescent intercalator displacement (FID) assay shows that a trimer with prolinamide side chains at the para-position of the benzene ring can discriminate between different quadruplex structures and exhibits the highest binding affinity towards the c-MYC G-quadruplex structure. Molecular modeling studies reveal that the prolinamide trimer stacks upon the terminal G-quartet of the c-MYC G-quadruplex. Atomic force microscopy (AFM) analysis reveals that the tris-prolinamide ligand can be used to regulate the assembly of novel supramolecular nanoarchitectures. Further, in vitro cellular studies with human hepatocellular carcinoma (HepG2) cells indicate that the tris-prolinamide derivatives can inhibit cell proliferation and reduce c-MYC expression in cancer cells.
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DNA/química , DNA/metabolismo , Quadruplex G , Prolina/análogos & derivados , Proteínas Proto-Oncogênicas c-myc/genética , Desenho de Fármacos , Células Hep G2 , Humanos , Ligantes , Modelos Moleculares , Prolina/química , Prolina/metabolismo , Especificidade por Substrato , Triazóis/químicaRESUMO
Background Complex bulbar urethral strictures are a heterogeneous group, including those secondary to radiotherapy, failed previous open urethroplasty, and total bulbar necrosis following pelvic trauma. Traditional urethroplasty techniques in this group are unpredictable. We describe a novel technique of a buccal mucosa-prelaminated radial forearm free flap urethroplasty, which seeks to improve the quality of life for this group of patients. Methods Known, reliable techniques from two surgical specialties were combined to create a novel surgical solution, consisting of a radial forearm free flap prelaminated with buccal mucosa. Prospective data were collected on patient and stricture characteristics, complications, and results, including voiding flow rates, urethrography, and cystourethroscopy. Success was defined as the ability to void per urethra. The procedure was performed in four patients, previously considered unreconstructable and who were suprapubic catheter dependent. Results Microsurgical transfer was successful in all four cases. All patients were voiding per urethra and remained catheter free at a minimum of 12-month follow-up. There was no significant donor morbidity and all patients were able to return to their usual occupation. Mean voiding flow rates were 17.3 mL/s. Flexible cystoscopy revealed well-vascularized, patent neomucosa. Conclusions We demonstrate proof of concept for a novel technique of microsurgical urethroplasty. We believe this technique may have widespread application in the treatment of radiation-induced and other complex urethral strictures where traditional urethroplasty has limited success.
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Antebraço/irrigação sanguínea , Retalhos de Tecido Biológico/irrigação sanguínea , Microcirurgia , Mucosa Bucal/transplante , Estreitamento Uretral/cirurgia , Micção/fisiologia , Procedimentos Cirúrgicos Urológicos , Adulto , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Retorno ao Trabalho , Resultado do Tratamento , Estreitamento Uretral/fisiopatologia , Procedimentos Cirúrgicos Urológicos/métodosRESUMO
Dengue infection accompanied by unusual complications and manifestations has been described before. Here we report a case of dengue encephalitis who was IgM positive for dengue serology and had presented to us with only motor weakness after an acute febrile episode. Dengue presenting as encephalitis is in itself a very rare feature and that too, pure motor weakness has hardly ever been reported before.
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Dengue , Encefalite Viral , Adulto , Dengue/diagnóstico por imagem , Encefalite Viral/diagnóstico por imagem , Humanos , MasculinoRESUMO
A modular synthesis of l-proline derived peptidomimetics has been developed using the Cu(I) catalyzed Huisgen cycloaddition between an azido prolinamide with pyridine and benzene dicarboxamide containing dialkynes. Förster Resonance Energy Transfer (FRET) melting assay provided an initial indication that the pyridyl analogue can stabilize the c-KIT1 quadruplex DNA. A competitive FRET-melting assay and Fluorescent Intercalator Displacement (FID) assay suggest that the pyridyl ligand shows excellent selectivity for c-KIT1 quadruplex over duplex DNA and other investigated G-quadruplexes. Molecular docking studies indicate that the pyridyl ligand can adopt unique conformations upon binding to c-KIT1 quadruplex due to the presence of intramolecular hydrogen bonds. The pyridyl ligand can perturb cell cycle progression and induce necrotic cell death of human hepatocellular liver carcinoma HepG2 cells.
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Antineoplásicos/farmacologia , Quadruplex G , Neoplasias Hepáticas/patologia , Peptidomiméticos/química , Prolina/farmacologia , Bibliotecas de Moléculas Pequenas/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Sítios de Ligação , Ciclo Celular/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Transferência Ressonante de Energia de Fluorescência , Células Hep G2 , Humanos , Ligantes , Simulação de Acoplamento Molecular , Estrutura Molecular , Prolina/síntese química , Prolina/química , Bibliotecas de Moléculas Pequenas/síntese química , Bibliotecas de Moléculas Pequenas/química , Relação Estrutura-AtividadeAssuntos
Varicela , Herpes Zoster , Mielite Transversa , Infecção pelo Vírus da Varicela-Zoster , Aciclovir , HumanosRESUMO
Enhancer, a distal cis-regulatory element controls gene expression. Experimental prediction of enhancer elements is time-consuming and expensive. Consequently, various inexpensive deep learning-based fast methods have been developed for predicting the enhancers and determining their strength. In this paper, we have proposed a two-stage deep learning-based framework leveraging DNA structural features, natural language processing, convolutional neural network, and long short-term memory to predict the enhancer elements accurately in the genomics data. In the first stage, we extracted the features from DNA sequence data by using three feature representation techniques viz., k-mer based feature extraction along with word2vector based interpretation of underlined patterns, one-hot encoding, and the DNAshape technique. In the second stage, strength of enhancers is predicted from the extracted features using a hybrid deep learning model. The method is capable of adapting itself to varying sizes of datasets. Also, as proposed model can capture long-range sequencing patterns, the robustness of the method remains unaffected against minor variations in the genomics sequence. The method outperforms the other state-of-the-art methods at both stages in terms of performance metrics of prediction accuracy, specificity, Mathew's correlation coefficient, and area under the ROC curve. In summary, the proposed method is a reliable method for enhancer prediction.
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Benchmarking , DNA , Sequência de Bases , DNA/genética , Genômica , Processamento de Linguagem Natural , Elementos Facilitadores Genéticos/genéticaRESUMO
Background: Diabetes is a major burden globally, more commonly so in developing countries, as its complications are detected relatively late due to underdeveloped healthcare systems. These complications, when detected, are more or less irreversible, thereby leading to increased morbidity and mortality. Among these, complications related to bones (mainly osteoporosis) start fairly early (even in the prediabetes stage) but are less emphasized, nonetheless are major contributors to morbidity in diabetics due to increased fracture risk. One of the novel bone markers recently discovered is sclerostin, which helps in the assessment of the effect of hyperglycemia on bone homeostasis. Bone mineral density (BMD) by DXA scan is a good tool to assess the status of bone health but requires modern expensive radiological equipment. In this study, we wanted to see the correlation of serum levels of sclerostin to BMD so that by a simple serum investigation, early detection of poor bone quality in treatment-naive prediabetics can be done. Objective: The aim of the study was to measure serum levels of sclerostin in prediabetics, compare them with normoglycemic controls, and find the correlation of serum levels of sclerostin with BMD. Methods: 50 prediabetic patients and 50 age, sex, blood pressure, and BMI-matched controls were recruited in the study. In both the groups, serum levels of fasting blood glucose and postprandial glucose, glycated hemoglobin (HbA1c), Vitamin D, fasting insulin, and serum sclerostin levels were measured in both groups using ELISA. The obtained values were compared between the two groups. Bone mineral density is measured by DXA scan in cases and a correlation between BMD and serum levels of sclerostin was observed. Results: Serum sclerostin was significantly higher in the cases [18.22 (19.42) ng/ml] compared to the control group [11.08 (4.73) ng/ml] with a P value of 0.013. The mean of BMD in prediabetes is 1.06 g/cm2, T score is - 1.02, and Z score is - 0.59. There was a significant negative correlation between serum sclerostin levels and BMD in prediabetes (r = -0.404, P < 0.001). Conclusion: Serum levels of sclerostin are increased in prediabetes and correlate well with low BMD in prediabetes, and can therefore be used for early recognition of osteoporosis and fractures in diabetes.
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Background: Neuregulin-4 is a recently recognized adipokine acting as ligands to tyrosine kinases receptor of the Erb B family. This adipose tissue augmented endocrine factor participates in the modulation of lipid and glucose metabolism and energy homeostasis. This novel adipokine is associated with insulin resistance, dyslipidemia, obesity, oxidative stress, and inflammation. Objective: The study aimed to compare plasma levels of neuregulin-4 in newly diagnosed type 2 diabetes mellitus as compared to matched controls and to correlate with glycemic and lipid parameters. Materials and Methods: 100 newly diagnosed T2DM patients and 100 age, sex, and BMI-matched controls after fulfilling all exclusion and inclusion criteria were included in the study. Fasting and postprandial blood glucose levels, glycated hemoglobin (HbA1c), and fasting plasma insulin levels were measured in both cases and controls. HOMA-IR values in both groups were calculated using fasting glucose and insulin levels. Results: Mean levels of plasma neuregulin-4(pg/mL) in newly diagnosed T2DM were 7949.76 ± 949.76) pg/ml, which was significantly lower as compared to 9143 ±949.76) pg/ml in the control group (P-value <.0001). In the present study, a significant negative correlation was seen between plasma neuregulin-4 (pg/mL) with fasting blood sugar, postprandial blood sugar, HbA1C, and HOMA-IR with a correlation coefficient of -0.303, -0.416, -0.433, and -0.514, respectively. Moreover, a significant positive correlation was seen between plasma neuregulin-4 (pg/mL) with HDL with a correlation coefficient of 0.216. A significant negative correlation was seen between plasma neuregulin-4 (pg/mL) and LDL, with a correlation coefficient -0.208. Conclusion: Neuregulin levels are significantly lower in diabetics as compared to controls. There levels correlated inversely with HbA1C and HOMA IR.
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BACKGROUND: Ketamine is most easily and inexpensively administered by the oral route and in racemic form. Oral racemic ketamine may be an important approach to the emergency management of suicide risk in clinical settings, especially in third world countries, that have a limited range of available healthcare resources. METHODS: In a prospective, uncontrolled, open-label investigation, we studied 30 severely depressed inpatients who consented to participate in a pilot hospital service offering ketamine for management of high suicide risk. Patients sipped a solution of racemic ketamine (150 mg) across 10-15 min in 3 alternate day sessions. Patients were assessed using the Modified Scale for Suicidal Ideation (MSSI), Montgomery-Asberg Depression Rating Scale (MADRS), and Clinical Global Improvement-Severity (CGI-S) scale at baseline and 1 day after the last ketamine session. RESULTS: There was statistically and clinically significant improvement on all outcomes. Mean (standard deviation) MSSI scores dropped from 25.1(1.8) to 17.3(5.6), MADRS scores from 28.8(3.4) to 21.9(3.6), and CGI-S scores from 6.0(0.2) to 3.6(0.9). At endpoint, MSSI scores had dropped from severe to low or mild-to-moderate in 67% of patients. The 90 ketamine sessions were uneventful; the treatment was well tolerated and no patient dropped out. CONCLUSION: Oral racemic ketamine may be a useful and potentially life-saving approach to the emergency management of severely depressed patients at high risk of suicide.