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BACKGROUND: Anemia during pregnancy can complicate maternal and neonatal health and even lead to fatal consequences if not diagnosed early on. Around 99% of women who face maternal mortality are from middle or low-income countries. Early screening of anemia could facilitate improved health outcomes in pregnant women. Point of care techniques are preferred due to their ability to provide results rapidly and because they can be used by personnel with minimal or no training. Such techniques are especially useful in resource-constrained settings like rural parts of developing countries. OBJECTIVES: The aim of the study was to develop a tool using an Artificial Neural Network (ANN) to estimate hemoglobin values using color information recorded from blood sample images. Our method utilizes inexpensive consumables and a simple image acquisition setup that can be assembled easily. METHODS: This study explores a neural network model to estimate the hemoglobin content in an individual's blood sample. Blood samples were collected from 86 volunteers and the images of blood drops were obtained using an image acquisition setup designed by the team. The color intensity values calculated from the blood drop images were used as feature descriptors for the samples. The features obtained from our samples were consequently fed to the Artificial Neural Network. RESULTS: Our neural network that gives the best result has the architecture of 11 neurons in each of the 5 layers. The best model gave estimated hemoglobin levels by analyzing color of blood samples with an accuracy of ±1.8 g/dl Limits of agreement (LOA) and bias 0.03 g/dl (with mean error of 0.75 g/dl). The model was subsequently tested with a validation set prepared from an additional 65 samples. The estimated hemoglobin levels gave an accuracy of +2 g/dl to -1.9 g/dl Limits of agreement (LOA) and bias 0.06 g/dl (with mean error of 0.78 g/dl). CONCLUSION: Optimization of sensitivity and specificity has been able to achieve the sensitivity and specificity values as 95.5% and 52% respectively. These results are at par with the contemporary measurement techniques indicating that our method can be used as a workable screening technique itself.
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Anemia , Recém-Nascido , Humanos , Feminino , Gravidez , Anemia/diagnóstico por imagem , Hemoglobinas/análise , Sensibilidade e Especificidade , Programas de RastreamentoRESUMO
BACKGROUND: Hypercalcaemia is a serious complication of lung cancer. A quality improvement project (QIP) was designed based on guidance from the American College of Chest Physician and the European Respiratory Society who recommend measuring serum calcium for patients referred with suspected lung cancer. METHOD: Seventy-two patients were included in the initial data to ascertain the delay between referral to the lung cancer pathway and obtaining serum calcium levels as part of the initial work-up. New data were then collected after each intervention (including presentations at weekly respiratory multidisciplinary team meetings, posters within clinical areas and a hospital trust screensaver) to evaluate the delay. RESULTS: Initially, 11.1% (n=8) did not have serum calcium measured at any point; two of which had lung cancer (including one metastatic malignancy). Of those who had serum calcium measured, there was a median delay of 13 days between first suspicion and obtaining serum calcium. After all the interventions were put in place, patients had a median of 7 days' delay (p=0.001). CONCLUSION: This QIP design was based on continued feedback to improve the care of patients suspected of lung cancer. Although there was a significant reduction in delays post-intervention, increasing awareness in the community is suggested to maintain these improvements.
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BACKGROUND AND OBJECTIVE: In this study, we have analysed pretreatment positron-emission tomography/ computed tomography (PET/CT) images of head and neck squamous cell carcinoma (HNSCC) patients. We have used a publicly available dataset for our analysis. The clinical features of the patient, PET quantitative parameters, and textural indices from pretreatment PET-CT images are selected for the study. The main objective of the study is to use classifiers to predict the outcome for HNSCC patients and compare the performance of the model with the conventional statistical model (CoxPH). METHODS: We have applied a 40% fixed SUV threshold method for tumour delineation. Clinical features of each patient are provided in the dataset, and other features are calculated using LIFEx software. For predicting the outcome, we have implemented three classifiers - Random Forest classifier, Gradient Boosted Decision tree (GBDT) and Decision tree classifier. We have trained each model using 93 data points and test the model performance using 39 data points. The best model - GBDT is chosen based on the performance metrics. RESULTS: It is observed that typically three features: MTV (Metabolic tumour Volume), primary tumour site and GLCM_correlation are significant for prediction of survival outcome. For testing cohort, GBDT achieves a balanced accuracy of 88%, where conventional statistical model reported a balanced accuracy of 81.5%. CONCLUSIONS: The proposed classifier achieves higher accuracy than the state of the art technique. Using this classifier we can estimate the HNSCC patient's outcome, and depending upon the outcome treatment policy can be selected.
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Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Carcinoma de Células Escamosas/diagnóstico por imagem , Fluordesoxiglucose F18 , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico por imagemRESUMO
Loss of glutamatergic synapses is thought to be a key cellular pathology associated with neuropsychiatric disorders including schizophrenia (SCZ) and major depressive disorder (MDD). Genetic and cellular studies of SCZ and MDD using in vivo and in vitro systems have supported a key role for dysfunction of excitatory synapses in the pathophysiology of these disorders. Recent clinical studies have demonstrated that the estrogen, 17ß-estradiol can ameliorate many of the symptoms experienced by patients. Yet, to date, our understanding of how 17ß-estradiol exerted these beneficial effects is limited. In this study, we have tested the hypothesis that 17ß-estradiol can restore dendritic spine number in a cellular model that recapitulates the loss of synapses associated with SCZ and MDD. Ectopic expression of wildtype, mutant or shRNA-mediated knockdown of Disrupted in Schizophrenia 1 (DISC1) reduced dendritic spine density in primary cortical neurons. Acute or chronic treatment with 17ß-estradiol increased spine density to control levels in neurons with altered DISC1 levels. In addition, 17ß-estradiol reduced the extent to which ectopic wildtype and mutant DISC1 aggregated. Furthermore, 17ß-estradiol also caused the enrichment of synaptic proteins at synapses and increased the number of dendritic spines containing PSD-95 or that overlapped with the pre-synaptic marker bassoon. Taken together, our data indicates that estrogens can restore lost excitatory synapses caused by altered DISC1 expression, potentially through the trafficking of DISC1 and its interacting partners. These data highlight the possibility that estrogens exert their beneficial effects in SCZ and MDD in part by modulating dendritic spine number.
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Transtorno Depressivo Maior , Estradiol , Espinhas Dendríticas , Estradiol/farmacologia , Estrogênios , Humanos , SinapsesRESUMO
BACKGROUND: The study aimed at assessing the prevalence and clinical profile of minimal hepatic encephalopathy (MHE) in patients with cirrhosis using neuropsychological assessment and at understanding the management practices of MHE in the Indian clinical setting. METHODS: This cross-sectional, clinicoepidemiological study conducted at 20 sites enrolled liver cirrhosis patients with Grade 0 hepatic encephalopathy according to West-Haven Criteria. Patients were subjected to mini-mental state examination and those with a score of ≥24 were assessed using psychometric hepatic encephalopathy score. Short Form-36 questionnaire was administered to assess the impact on health-related quality of life. RESULTS: Of the 1260 enrolled patients, 1114 were included in the analysis. The mean age was 49.5 years and majority were males (901 [81%]). The prevalence of MHE was found to be 59.7% (665/1114) based on the psychometric hepatic encephalopathy score of ≤-5. Alcohol-related liver disease was the most common etiology (482 [43.27%]) followed by viral infection (239 [21.45%]). Past smokers as well as those currently smoking were more likely to have MHE than nonsmokers. A significant association was found between tobacco chewing, smoking, alcohol consumption, diabetes, and the presence of MHE. Multivariable analysis revealed smoking as the only parameter associated with MHE. A total of 300 (26.9%) patients were on prophylaxis with lactulose/lactitol or rifaximin. These patients were less likely to have MHE as compared to those not on prophylaxis (odds ratio, 0.67; 95% confidence interval, 0.50-0.88; P = 0.005). CONCLUSION: The disease burden of MHE is quite substantial in patients with cirrhosis with no apparent cognitive defect. Smoking, whether past or current, has significant association with the presence of MHE. Although MHE has been shown to adversely affect quality of life, prophylaxis for MHE is not routinely practiced in the Indian setting.The study has been registered under clinical trials registry of India (CTRI/2014/01/004306).
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Estrogen plays a critical role in many physiological processes and exerts profound effects on behavior by regulating neuronal excitability. While estrogen has been established to exert effects on dendritic morphology and excitatory neurotransmission its role in regulating neuronal inhibition is poorly understood. Fast synaptic inhibition in the adult brain is mediated by specialized populations of γ-c aA receptors (GABAARs) that are selectively enriched at synapses, a process dependent upon their interaction with the inhibitory scaffold protein gephyrin. Here we have assessed the role that estradiol (E2) plays in regulating the dynamics of GABAARs and stability of inhibitory synapses. Treatment of cultured cortical neurons with E2 reduced the accumulation of GABAARs and gephyrin at inhibitory synapses. However, E2 exposure did not modify the expression of either the total or the plasma membrane GABAARs or gephyrin. Mechanistically, single-particle tracking revealed that E2 treatment selectively reduced the dwell time and thereby decreased the confinement of GABAARs at inhibitory synapses. Consistent with our cell biology measurements, we observed a significant reduction in amplitude of inhibitory synaptic currents in both cultured neurons and hippocampal slices exposed to E2, while their frequency was unaffected. Collectively, our results suggest that acute exposure of neurons to E2 leads to destabilization of GABAARs and gephyrin at inhibitory synapses, leading to reductions in the efficacy of GABAergic inhibition via a postsynaptic mechanism.
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Estradiol/farmacologia , Inibição Neural/efeitos dos fármacos , Receptores de GABA-A/metabolismo , Sinapses/efeitos dos fármacos , Sinapses/metabolismo , Animais , Proteínas de Transporte/farmacologia , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Células Cultivadas , Feminino , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Masculino , Proteínas de Membrana/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Ratos , Transmissão Sináptica/efeitos dos fármacosRESUMO
We present a case of a man in his late 60s, who had spent 3-4â months of the year in rural Spain, presenting with intermittent hoarseness of voice. He had a background of asthma and bronchiectasis, and was taking inhaled corticosteroids. His dysphonia was initially managed as bronchiectasis with little improvement. Bronchoscopy revealed a cystic lesion on his left vocal fold, and tissue biopsy revealed Leishmania amastigotes. This confirmed a diagnosis of laryngeal leishmaniasis. We propose that this is likely secondary to his inhaled corticosteroid therapy. The infection was treated with a 30-day course of miltefosine, and at most recent follow-up the patient was deemed free from leishmanial infection.
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Corticosteroides/administração & dosagem , Corticosteroides/uso terapêutico , Asma/tratamento farmacológico , Doenças da Laringe/parasitologia , Leishmaniose/diagnóstico , Leishmaniose/tratamento farmacológico , Fosforilcolina/análogos & derivados , Administração por Inalação , Idoso , Antieméticos/uso terapêutico , Antiprotozoários/uso terapêutico , Broncoscopia/métodos , Disfonia/tratamento farmacológico , Disfonia/parasitologia , Disfonia/fisiopatologia , Rouquidão/tratamento farmacológico , Rouquidão/parasitologia , Rouquidão/fisiopatologia , Humanos , Doenças da Laringe/tratamento farmacológico , Doenças da Laringe/fisiopatologia , Leishmaniose/fisiopatologia , Masculino , Fosforilcolina/uso terapêutico , Proclorperazina/uso terapêutico , Espanha , Viagem , Resultado do Tratamento , Prega VocalRESUMO
We present the case of a 48-year-old man with an extensive cannabis smoking history who presented with pleuritic chest pain. A chest X-ray revealed multiple large, apical lung bullae with fluid levels, an appearance consistent with infection. Lung function tests showed moderate airflow obstruction and decreased gas transfer. The infection was treated with a prolonged course of antimicrobials, and the patient followed up by respiratory physicians.
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Candidíase/etiologia , Dor no Peito/etiologia , Pneumopatias Fúngicas/etiologia , Fumar Maconha/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Pleurais/etiologia , Tomografia Computadorizada por Raios XRESUMO
In schizophrenia, cognitive dysfunction is highly predictive of poor patient outcomes and is not responsive to current medications. Postmortem studies have suggested that cognitive deficits in schizophrenia are correlated with modifications in the number and size of inhibitory synapses. To test if these modifications lead to cognitive deficits, we have created a dominant-negative virus [adeno-associated (AAV)-DN1] that disrupts the clustering of γ-aminobutyric acid type A receptors (GABA(A)Rs) at postsynaptic inhibitory specializations. When injected into the frontal cortex of mice, AAV-DN1 impairs GABA(A)R α2 subunit and GABA transporter 1 (GAT-1) clustering, but increases GABA(A)R α1 subunit clustering on the perisomatic region, with no influence on axon-initial segment clustering. Mice expressing AAV-DN1 have prepulse inhibition deficits and impairments in working memory. Significantly, these behavioral deficits are paralleled by a reduction in electroencephalography γ-power. Collectively, our study provides functional evidence revealing that GABAergic synapses in the prefrontal cortex directly contribute to cognition and γ-power.
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Cognição/fisiologia , Dependovirus/genética , Modelos Animais de Doenças , Lobo Frontal/metabolismo , Receptores de GABA-A/metabolismo , Esquizofrenia/metabolismo , Animais , Eletroencefalografia , Proteínas da Membrana Plasmática de Transporte de GABA/metabolismo , Engenharia Genética/métodos , Vetores Genéticos/genética , Imuno-Histoquímica , Camundongos , Esquizofrenia/patologia , Transdução de Sinais/fisiologiaRESUMO
Functional α7 nicotinic acetylcholine receptors (AChRs) do not assemble efficiently in cells transfected with α7 subunits unless the cells are also transfected with the chaperone protein RIC-3. Despite the presence of RIC-3, large amounts of these subunits remain improperly assembled. Thus, additional chaperone proteins are probably required for efficient assembly of α7 AChRs. Cholinergic ligands can act as pharmacological chaperones to promote assembly of mature AChRs and upregulate the amount of functional AChRs. In addition, we have found that the chemical chaperones 4-phenylbutyric acid (PBA) and valproic acid (VPA) greatly increase the amount of functional α7 AChRs produced in a cell line expressing both α7 and RIC-3. Increased α7 AChR expression allows assay of drug action using a membrane potential-sensitive fluorescent indicator. Both PBA and VPA also increase α7 expression in the SH-SY5Y neuroblastoma cell line that endogenously expresses α7 AChRs. VPA increases expression of endogenous α7 AChRs in hippocampal neurons but PBA does not. RIC-3 is insufficient for optimal assembly of α7 AChRs, but provides assay conditions for detecting additional chaperones. Chemical chaperones are a useful pragmatic approach to express high levels of human α7 AChRs for drug selection and characterization and possibly to increase α7 expression in vivo.
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Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Multimerização Proteica , Receptor Nicotínico de Acetilcolina alfa7/metabolismo , Linhagem Celular , Membrana Celular/metabolismo , Células Cultivadas , Expressão Gênica , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Chaperonas Moleculares/metabolismo , Chaperonas Moleculares/farmacologia , Ligação Proteica , Multimerização Proteica/efeitos dos fármacos , Subunidades Proteicas/genética , Subunidades Proteicas/metabolismo , Receptor Nicotínico de Acetilcolina alfa7/química , Receptor Nicotínico de Acetilcolina alfa7/genéticaRESUMO
Omental gangrene is an infrequent cause of acute abdomen with unclear etiology. Hypercoagualable states like protein C or protein S deficiency have never been implicated in the etiology of omental gangrene. We present this case report of a patient having protein C and protein S deficiency presenting with omental gangrene and extensive porto mesenteric thrombosis.
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Mycotic aneurysm formation is a rare and potentially fatal sequela of bacteremia. We present the cases of 2 octogenarians who had surgically confirmed mycotic aneurysms that involved the ascending aorta, with contained rupture (pseudoaneurysm). Neither patient had evidence of valvular endocarditis. Patient 1, an 82-year-old man, had streptococcal bacteremia. Imaging confirmed a mycotic aneurysm of the ascending aorta, and resection was successful. Patient 2, an 83-year-old woman, had recurrent staphylococcal bacteremia and progressive widening of the mediastinum, and imaging revealed a mycotic pseudoaneurysm. She underwent surgical repair with use of a bovine pericardial patch, but she died 2 weeks later because of patch dehiscence.We did not initially suspect mycotic aneurysm in either patient. Despite the availability of accurate, noninvasive imaging techniques, strong clinical suspicion is required for the early diagnosis of mycotic aneurysm.
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Aneurisma Infectado/diagnóstico , Aneurisma Aórtico/diagnóstico , Infecções Estafilocócicas/diagnóstico , Infecções Estreptocócicas/diagnóstico , Idoso de 80 Anos ou mais , Aneurisma Infectado/microbiologia , Aneurisma Infectado/cirurgia , Aneurisma Aórtico/microbiologia , Aneurisma Aórtico/cirurgia , Aortografia/métodos , Diagnóstico Precoce , Ecocardiografia Doppler em Cores , Ecocardiografia Transesofagiana , Evolução Fatal , Feminino , Humanos , Masculino , Pericárdio/transplante , Valor Preditivo dos Testes , Recidiva , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/cirurgia , Infecções Estreptocócicas/microbiologia , Infecções Estreptocócicas/cirurgia , Deiscência da Ferida Operatória/etiologia , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Procedimentos Cirúrgicos Vasculares/efeitos adversosRESUMO
Various colonic side-effects of herbal enema have been reported in literature ranging from mild abdominal discomfort to self-limiting haemorrhagic colitis. It rarely requires blood transfusion or subtotal colectomy. We report a 57-year-old male patient developing severe ileo-colitis with persistent massive rectal bleeding immediately after herbal enema administration for the treatment of chronic constipation and was resistant to conservative management. Patient was managed successfully with emergency total laparoscopic colectomy. Post-operative recovery of the patient was excellent.
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Mechanisms that regulate early events in the biogenesis of the alpha7 nicotinic acetylcholine receptor (alpha7 AChR) are not well understood. Data presented here show that single amino acid mutations in the cytoplasmic loop of the alpha7 AChR, between position 335 and 343, abolish or attenuate expression of mature pentameric alpha7 AChRs in both human embryonic kidney tsA201 (HEK) and neuronal SH-SY5Y cells. Although the number of mature alpha7 AChRs is increased significantly in the presence of the chaperone protein resistant to inhibitors of cholineesterase-3 in HEK cells, sucrose gradient sedimentation reveals that the vast majority of alpha7 subunits are aggregated or improperly assembled. Transfection of alpha7 AChRs in SH-SY5Y cells, which endogenously express the alpha7 AChR, results in a much larger fraction of subunits assembled into mature AChRs. Thus, efficient assembly of alpha7 AChRs is influenced by several regions of the large cytoplasmic domain, as well perhaps by other parts of its structure, and requires as yet unknown factors not required by other AChR subtypes.
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Mutação/genética , Receptores Nicotínicos/genética , Receptores Nicotínicos/metabolismo , Aconitina/análogos & derivados , Aconitina/metabolismo , Sequência de Aminoácidos , Animais , Bungarotoxinas/metabolismo , Linhagem Celular , Galinhas , Expressão Gênica/genética , Humanos , Imunoprecipitação/métodos , Membranas Intracelulares/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Leucina/genética , Neuroblastoma/metabolismo , Neuroblastoma/patologia , Ligação Proteica/efeitos dos fármacos , Radioisótopos/metabolismo , Relação Estrutura-Atividade , Transfecção/métodos , Receptor Nicotínico de Acetilcolina alfa7RESUMO
The structural determinants of nicotinic acetylcholine receptor (AChR) trafficking have yet to be fully elucidated. Hydrophobic residues occur within short motifs important for endoplasmic reticulum (ER) export or endocytotic trafficking. Hence, we tested whether highly conserved hydrophobic residues, primarily leucines, in the cytoplasmic domain of the alpha4beta2 AChR subunits were required for cell surface expression of alpha4beta2 AChRs. Mutation of F350, L351, L357, and L358 to alanine in the alpha4 AChR subunit attenuates cell surface expression of mutant alpha4beta2 AChRs. Mutation of F342, L343, L349, and L350 to alanine at homologous positions in the beta2 AChR subunit abolishes cell surface expression of mutant alpha4beta2 AChRs. The hydrophobic nature of the leucine residue is a primary determinant of its function because mutation of L343 to another hydrophobic amino acid, phenylalanine, in the beta2 AChR subunit only poorly inhibits trafficking of mutant alpha4beta2 AChR to the cell surface. All mutant alpha4beta2 AChRs exhibit high-affinity binding for [3H]epibatidine. In both tsA201 cells and differentiated SH-SY5Y neural cells, wild-type alpha4beta2 AChRs colocalize with the Golgi marker giantin, whereas mutant alpha4beta2 AChRs fail to do so. The striking difference between mutant alpha4 versus mutant beta2 AChR subunits on cell surface expression of mutant alpha4beta2 AChRs points to a cooperative or regulatory role for the alpha4 AChR subunit and an obligatory role for the beta2 AChR subunit in ER export. Collectively, our results identify, for the first time, residues within AChR subunits that are essential structural determinants of alpha4beta2 AChR ER export.