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PURPOSE: In patients with diabetes, unrecognised hypertension is a serious problem risk factor for the development and progression of chronic complications. The study aimed to determine the prevalence of masked hypertension in normotensive diabetic patients, the factors affecting it, and its association with diabetes complications using ambulatory blood pressure monitoring (ABPM). MATERIALS AND METHODS: A cross-sectional observational study was conducted on 150 normotensive diabetic patients. Patients were subjected to an interview and clinical examination to record demographic data, epidemiological data, and significant past history. ABPM was performed for each patient. Urine samples, echocardiogram, and ophthalmologic fundoscopy were done to check for diabetes-related complications. RESULTS: The mean age of all participants was 56.7 ± 7.8 years. A total of 93 patients (62%) were males. 99 (66%) patients had masked hypertension. A total of 85 (56.7%) were non-dippers, 49 (32.7%) were dippers, 1 (0.7%) was extreme dipper and 15 (10%) were reverse dippers. Non-dipping and reverse dipping were associated with concentric left ventricular hypertrophy LVH (p < .001). Masked hypertension was associated with concentric LVH (p = .001) and nephropathy (p =.008) whereas, nocturnal hypertension was associated with concentric LVH (p = .001) and nephropathy (p =.003). CONCLUSIONS: A single office blood pressure (BP) reading cannot rule out hypertension in patients with diabetes. Regardless of hypertension, clinicians should have all patients, especially patients with diabetes, undergo ABPM at least once. Masked hypertension, changes in nocturnal dipping and other phenomena that raise the risk of diabetes complications but cannot be measured by office BP can be measured by ABPM, and thus ABPM can provide a good prognostic benefit.
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Complicações do Diabetes , Diabetes Mellitus Tipo 2 , Hipertensão , Hipertensão Mascarada , Pressão Sanguínea/fisiologia , Monitorização Ambulatorial da Pressão Arterial , Ritmo Circadiano , Estudos Transversais , Complicações do Diabetes/complicações , Diabetes Mellitus Tipo 2/complicações , Feminino , Humanos , Hipertrofia Ventricular Esquerda/complicações , Hipertrofia Ventricular Esquerda/etiologia , Masculino , Hipertensão Mascarada/complicações , Hipertensão Mascarada/diagnóstico , Pessoa de Meia-IdadeRESUMO
Nanoparticles of iron oxide, with diameters beteween 1 to 100 nm, have notable implications for human health and well being. In the current study, we have investigated the effects of iron oxide nanoparticles (IONP) exposure on general physiology and health of adult Wistar rats. IONP used in the study had spherical shape and average size in the range of 15-20 nm. A total of eight groups of rats were repeatedly injected with 0 (control), 20, 40, and 80 mg IONP per kg body weight intraperitoneally under two different exposure schemes (sub-acute and sub-chronic). IONP exposure caused significant changes in lungs, liver, and kidney indices in both exposure schemes. Sub-acute exposure did not affect body weight gain in treated rats, but longer duration exposure was responsible for significant reduction in body weight. Mesenteries, visceral fatty tissues, and visceral peritoneal membranes demonstrated apparent accumulations of IONP in a dose and time-dependent manner. Hematological analysis showed that total RBC count, hemoglobin content, hematocrit, mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC) and mean platelet volume (MPV) were not affected by IONP exposure. Total lymphocyte count, however, was elevated in low- and mid-dose treated rats, but not in high-dose group. Serum lactate dehydrogenase (LDH) increased significantly in rats treated with mid and high doses as compared to control. Serum creatinine and blood urea nitrogen levels were also significantly altered in treated rats. Histological study found significant hepatic damage and mild spleen toxicity. Our report suggests that IONP exhibit significant toxicity in rats.
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Compostos Férricos/toxicidade , Nanopartículas/toxicidade , Animais , Nitrogênio da Ureia Sanguínea , Creatinina/sangue , Relação Dose-Resposta a Droga , L-Lactato Desidrogenase/sangue , Fígado/patologia , Masculino , Ratos Wistar , Baço/patologiaRESUMO
BACKGROUND: Core promoter controls transcription initiation. However, little is known for core promoter diversity in the human genome and its relationship with diseases. We hypothesized that as a functional important component in the genome, the core promoter in the human genome could be under evolutionary selection, as reflected by its highly diversification in order to adjust gene expression for better adaptation to the different environment. RESULTS: Applying the "Exome-based Variant Detection in Core-promoters" method, we analyzed human core-promoter diversity by using the 2682 exome data sets of 25 worldwide human populations sequenced by the 1000 Genome Project. Collectively, we identified 31,996 variants in the core promoter region (- 100 to + 100) of 12,509 human genes ( https://dbhcpd.fhs.um.edu.mo ). Analyzing the rich variation data identified highly ethnic-specific patterns of core promoter variation between different ethnic populations, the genes with highly variable core promoters, the motifs affected by the variants, and their involved functional pathways. eQTL test revealed that 12% of core promoter variants can significantly alter gene expression level. Comparison with GWAS data we located 163 variants as the GWAS identified traits associated with multiple diseases, half of these variants can alter gene expression. CONCLUSION: Data from our study reals the highly diversified nature of core promoter in the human genome, and highlights that core promoter variation could play important roles not only in gene expression regulation but also in disease predisposition.
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Regulação da Expressão Gênica , Genoma Humano , Evolução Biológica , Expressão Gênica , Humanos , Regiões Promotoras GenéticasRESUMO
BACKGROUND: The traditional medical system of Ayurveda is widely practiced in India. Using the treatment principles of Panchakarma, Ayurveda offers rehabilitation therapy for patients with stroke. Although Ayurvedic rehabilitation is popular and has proven benefits, the experiences of stroke survivors undergoing Ayurvedic rehabilitation have not yet been documented in the literature. PURPOSE: To explore the experience of stroke survivors during rehabilitation in an inpatient Ayurvedic facility. METHODS: A qualitative approach with a phenomenological method was used for the study. Semi-structured interviews were conducted with 6 patients who were post-stroke and receiving inpatient rehabilitation therapy in an Ayurvedic facility in India. Thematic analyses of the verbatim transcripts were done using Lindseth & Norberg's phenomenological methodology. RESULTS: The main themes that emerged were "aspiring for self-efficacy," "hopefulness" and "treatment acceptance," with subthemes such as "self-reliance," resilience," "finding meaning in life," "optimism," "spirituality," "therapeutic mileu" and "perceived social support." CONCLUSION: The study indicates that stroke survivors undergoing Ayurvedic rehabilitation therapy look forward to improved self-reliance and experience enhanced feelings of hope. The treatment modalities used for rehabilitation are acceptable to patients. Essentially, rehabilitation in an Ayurvedic facility provides a holistic uplift in the well-being stroke survivors.
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Ayurveda/métodos , Reabilitação do Acidente Vascular Cerebral/métodos , Acidente Vascular Cerebral/psicologia , Sobreviventes/psicologia , Humanos , Índia , Entrevistas como Assunto , Satisfação do Paciente , Pesquisa Qualitativa , Recuperação de Função Fisiológica , Reabilitação do Acidente Vascular Cerebral/psicologiaRESUMO
BRCA1 and BRCA2 play essential roles in maintaining the genome stability. Pathogenic germline mutations in these two genes disrupt their function, lead to genome instability and increase the risk of developing breast and ovarian cancers. BRCA mutations have been extensively screened in Caucasian populations, and the resulting information are used globally as the standard reference in clinical diagnosis, treatment and prevention of BRCA-related cancers. Recent studies suggest that BRCA mutations can be ethnic-specific, raising the question whether a Caucasian-based BRCA mutation information can be used as a universal standard worldwide, or whether an ethnicity-based BRCA mutation information system need to be developed for the corresponding ethnic populations. In this study, we used Chinese population as a model to test ethnicity-specific BRCA mutations considering that China has one of the latest numbers of breast cancer patients therefore BRCA mutation carriers. Through comprehensive data mining, standardization and annotation, we collected 1,088 distinct BRCA variants derived from over 30,000 Chinese individuals, one of the largest BRCA data set from a non-Caucasian population covering nearly all known BRCA variants in the Chinese population (https://dbBRCA-Chinese.fhs.umac.mo). Using this data, we performed multi-layered analyses to determine the similarities and differences of BRCA variation between Chinese and non-Chinese ethnic populations. The results show the substantial differences of BRCA data between Chinese and non-Chinese ethnicities. Our study indicates that the current Caucasian population-based BRCA data is not adequate to represent the BRCA status in non-Caucasian populations. Therefore, ethnic-based BRCA standards need to be established to serve for the non-Caucasian populations.
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Povo Asiático/genética , Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias da Mama/genética , Predisposição Genética para Doença/genética , Mutação em Linhagem Germinativa/genética , Neoplasias Ovarianas/genética , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
BACKGROUND: To evaluate the efficacy and tolerability of a poly-herbal formulation, Herbagut, for the treatment of gastrointestinal symptoms and its effect on quality of life parameters in patients presenting with self-reported, unsatisfactory bowel habits. METHODS: This was a randomised, double-blind, placebo-controlled trial. Fifty adults with self-reported unsatisfactory bowel habits, primarily characterised by chronic constipation were randomly allocated to take Herbagut or a matching placebo for 28 days. Efficacy of gastrointestinal changes was measured by the completion of a patient daily diary evaluating changes in stool type (Bristol Stool Form Scale), ease of bowel movements, and feeling of complete evacuation; and the Gastrointestinal Symptom Rating Scale (GSRS). Changes in quality of life were also examined using the World Health Organization Quality of Life - abbreviated version (WHOQOL-BREF), and the Patient Assessment of Constipation-Quality of Life (PAC-QOL). RESULTS: All participants completed the 28-day trial with no adverse events reported. Compared to the placebo, weekly bowel movements increased over time (p < .001), as did self-reported, normal bowel motions (76% vs 4%; p < .001). Self-reported incomplete evacuation was also lower in the Herbagut group compared to placebo (24% vs 76%; p = <.001). GSRS domain ratings for abdominal pain, constipation, diarrhoea, indigestion, and reflux also decreased significantly in people taking Herbagut compared to placebo (p < .001, for all domains). Moreover, quality of life significantly improved in the Herbagut group compared to placebo as indicated by significantly greater improvement in WHOQOL-BREF domain ratings for overall quality of life, social relations, environmental health, psychological health, and physical health (p < .001, for all domains); and PAC-QOL domain ratings for physical discomfort, psychosocial discomfort, worries and concerns, and life satisfaction (p < .001, for all domains). The changes were considered clinically meaningful as evidenced by their large effect sizes. CONCLUSION: Herbagut ingestion over a 28-day period resulted in improvements in several gastrointestinal symptoms and overall quality of life. Further investigation utilising larger sample sizes and diverse clinical and cultural populations are needed. TRIAL REGISTRATION: Clinical Trials Registry- India /2016/11/007479 . Registered 24 April 2015 (retrospectively registered).
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Constipação Intestinal/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Adulto , Constipação Intestinal/fisiopatologia , Defecação/efeitos dos fármacos , Método Duplo-Cego , Feminino , Trato Gastrointestinal/efeitos dos fármacos , Trato Gastrointestinal/fisiopatologia , Humanos , Índia , Masculino , Pessoa de Meia-Idade , Plantas Medicinais/química , Qualidade de VidaRESUMO
Introduction: Skeletal abnormalities in patients with post-traumatic facial deformities can generally be corrected with current craniomaxillofacial techniques. Delay in operative management secondary to associated life-threatening injuries, failure to appreciate the magnitude of the initial facial injury, inadequate operative treatment and operative complications contribute to their occurrence. Systematic evaluation of the midface, including the position of the globes, orbits, zygomatic (facial) width and occlusion, is of paramount importance. Some contour deficiencies can be camouflaged by relatively simple procedures, whereas some deformities may require osteotomies and repositioning of the displaced segments. Staged procedures need to be planned carefully so that previously diagnosed deformities are not concealed and new deformities are not created. The general goals of reconstruction are (i) to restore normal and anatomic bone alignment, (ii) to re-establish the underlying skeletal support prior to addressing soft tissue abnormalities and (iii) to replace missing tissue with like tissues. Conclusion: Restoring the normal bony architecture should be the initial consideration unless the quantity or quality of the soft tissue envelope is inadequate to protect the osseous reconstruction. The purpose of this study is to evaluate post-traumatic facial deformities and simulation and organization of all the treatment modalities in a sequential manner.
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Introduction: Mandible receives maximum impact following maxillofacial trauma. The dentate segment in particular is of importance as it has a direct bearing on the occlusive forces. The studies that have been carried out are either based on crude clinical evaluations or make use of elaborate and labor-intensive techniques. This study made use of T-scan analysis for objective identification of occlusive forces following mandibular fracture fixation. Materials and Methods: Eighty clinic-radiologically diagnosed cases of dentate segments of the mandible were considered, after random sampling method. The occlusion analysis was done by use of a T scan to obtain Relatively Occlusal Force. The procedure was repeated at 04-, 24-, 36-, and 48-weeks intervals. The data was recorded on Excel Spreadsheet (Microsoft Inc) and analysis was done using SPSS software. Results: The cases were predominantly males with a homogenous distribution of cases of age. The age versus gender distribution was more skewed in the female subgroup with a higher kurtosis value. Both evaluative (Pearson's) and inferential (paired t) tests were applied to reason the study. It was observed that the ROF values decreased in values as compared to pre-operative/post-treatment (Difference of Mean = 2.19, SE = 2.13) compared to 4 (Difference of Mean = -0.40 SE = 0.188),24 (Difference of Mean = -1.22, SE = 0.24) and 36 (Difference of Mean = -3.24, SE = 0.30) weeks, which however surpassed the pre-operative levels at 48 weeks post-operative period. This is suggestive of impending muscular imbalance in the initial periods. The surpass of 48 weeks may be due to optimal forces that were their pre-trauma. Conclusion: Mandibular fracture fixation is the most widely used and also a time-tested modality in the management of mandibular trauma. The evaluation of occlusive forces needs an understanding of their behavior following such fixation. The present study used T-scan analysis to objectify such forces and added extra insight apart from clinical evaluations of tooth contact and parafunctional movements.
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Background: Oral and maxillofacial surgery deals with wide range of oral defects, wound closure, tissue resection, and tissue reconstruction. The purpose of our study is to use amniotic membrane for closure of post surgery defect in patient of oral submucous fibrosis to utilize its growth factor and scaffold nature for effective healing and to evaluate effectiveness of amniotic membrane in treatment outcome. The objectives are to compare post-operative mouth opening, healing of amniotic membrane and buccal fat pad. Material and Method: Diagnosed patients with OSMF are divided into two surgical site Group I (n = 5patients)-Left side buccal mucosa in which resection of fibrous band with coronoidectomy followed by reconstruction of the mucosal defect with BFP. Group II-Right side buccal mucosa in which resection of fibrous band with coronoidectomy followed by reconstruction of the mucosal defect with freeze dried irradiated amniotic membrane. Result: This study suggested that in comparison to buccal fat pad flap, the HAM graft is a better option for oral reconstruction in terms of infection, graft failure, MMO, inflammation, pain. Outcome indicated that the HAM is biologically ideal graft for oral wounds and could be used as clinical alternative for various repair surgery for oral defects. Conclusion: The amniotic membrane was found easy to handle and easy to use with inherent hemostatic property which is observed in all patients. No patients had shown any evidence of any complications. Good pain control observed in patients throughout postoperative period.
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OBJECTIVE: Federated learning (FL) allows multiple distributed data holders to collaboratively learn a shared model without data sharing. However, individual health system data are heterogeneous. "Personalized" FL variations have been developed to counter data heterogeneity, but few have been evaluated using real-world healthcare data. The purpose of this study is to investigate the performance of a single-site versus a 3-client federated model using a previously described Coronavirus Disease 19 (COVID-19) diagnostic model. Additionally, to investigate the effect of system heterogeneity, we evaluate the performance of 4 FL variations. MATERIALS AND METHODS: We leverage a FL healthcare collaborative including data from 5 international healthcare systems (US and Europe) encompassing 42 hospitals. We implemented a COVID-19 computer vision diagnosis system using the Federated Averaging (FedAvg) algorithm implemented on Clara Train SDK 4.0. To study the effect of data heterogeneity, training data was pooled from 3 systems locally and federation was simulated. We compared a centralized/pooled model, versus FedAvg, and 3 personalized FL variations (FedProx, FedBN, and FedAMP). RESULTS: We observed comparable model performance with respect to internal validation (local model: AUROC 0.94 vs FedAvg: 0.95, P = .5) and improved model generalizability with the FedAvg model (P < .05). When investigating the effects of model heterogeneity, we observed poor performance with FedAvg on internal validation as compared to personalized FL algorithms. FedAvg did have improved generalizability compared to personalized FL algorithms. On average, FedBN had the best rank performance on internal and external validation. CONCLUSION: FedAvg can significantly improve the generalization of the model compared to other personalization FL algorithms; however, at the cost of poor internal validity. Personalized FL may offer an opportunity to develop both internal and externally validated algorithms.
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Teste para COVID-19 , COVID-19 , Humanos , Hospitais , Aprendizagem , Europa (Continente) , Estados UnidosRESUMO
Idiomarina sp. strain A28L was isolated from the alkaline brackish water of a high-altitude lake, Pangong Lake. Here, we present the draft genome of Idiomarina sp. strain A28L, which contains 2,591,567 bp with a G+C content of 45.5 mol% and contains 2,299 protein-coding genes and 56 structural RNAs.
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Alteromonadaceae/genética , Alteromonadaceae/isolamento & purificação , Água Doce/microbiologia , Genoma Bacteriano , Animais , Sequência de Bases , Água Doce/química , Dados de Sequência MolecularRESUMO
Rheinheimera sp. strain A13L, which has antimicrobial activity, was isolated from alkaline brackish water of the high-altitude Pangong Lake of Ladakh, India. Here we report the draft genome sequence of Rhienheimera sp. strain A13L (4,523,491 bp with a G+C content of 46.23%). The genome is predicted to contain genes for marinocine and colicin V production, which may be responsible for the antimicrobial activity of the strain.
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Chromatiaceae/genética , Chromatiaceae/isolamento & purificação , Água Doce/microbiologia , Genoma Bacteriano , Sequência de Bases , Água Doce/análise , Índia , Dados de Sequência MolecularRESUMO
A 13-year-old girl with perinatally acquired HIV infection was admitted to us with acute onset, right-sided hemiparesis of 30 days duration and right-sided myoclonic jerks of 2 days duration affecting the face, upper and lower limbs. On examination, she exhibited increased tone and a pyramidal pattern of weakness in her right upper and lower limbs, along with spontaneous multifocal myoclonic jerks in the affected area. IgG levels in the serum and cerebrospinal fluid for measles were significantly elevated. Brain MRI depicted T2-weighted-hyperintensities in the subcortical white matter. The electroencephalogram demonstrated evidence of lateralised long interval periodic discharges. This patient had no past behavioural problems or poor academic performance. This case underlines the fact that, though subacute sclerosing panencephalitis (SSPE) is a chronic disease, a rare fulminant form of SSPE might develop acutely and atypically, with an increased proclivity for HIV-infected patients.
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Infecções por HIV , Panencefalite Esclerosante Subaguda , Adolescente , Eletroencefalografia , Feminino , Infecções por HIV/complicações , Humanos , Neuroimagem , Paresia/etiologia , Panencefalite Esclerosante Subaguda/complicações , Panencefalite Esclerosante Subaguda/diagnósticoRESUMO
This 55-year-old man was admitted to the hospital with an insidious onset, progressive backward fall (due to severe truncal ataxia), dysarthria, stiffness in extremities, distal dominant muscle wasting along with behavioural changes and urinary incontinence. Clinical assessment indicated mild cognitive decline (Mini-Mental State Examination 22/27) with cerebellar, pyramidal and peripheral nerves involvement. On investigations, nerve conduction studies revealed symmetrical, sensorimotor peripheral neuropathy affecting both lower limbs. Brain and whole spine MRI revealed widespread cerebral and mild cerebellar atrophy, pons and medulla volume loss, and a normal spinal cord. Transthoracic echocardiography revealed concentric left ventricular hypertrophy. His gene analysis revealed eight GAA repeats on allele 1, and 37 GAA repeats on allele 2 in the first intron of the frataxin gene. Considering his clinical profile and genetic analysis, he was diagnosed as a case of very late-onset Friedreich's ataxia with likely compound heterozygous genotype.
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Ataxia de Friedreich , Atrofia de Múltiplos Sistemas , Alelos , Cerebelo , Ataxia de Friedreich/diagnóstico , Ataxia de Friedreich/genética , Genótipo , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Vogt-Koyanagi-Harada Disease (VKHD) is a rare systemic granulomatous autoimmune condition that affects melanocyte-rich organs including the eyes, inner ears, meninges, skin, and hair. VKHD causes chronic uveal inflammation and a loss in visual acuity in some patients. Patients generally respond well to steroid therapy. In our patient, we evidenced VKHD in the chronic recurrent stage at the time of presentation while the patient was on intermittent systemic steroid therapy. To date, no cases of VKHD have been reported in patients who were taking immunosuppressive medications. This study sheds light on the possibility that, in addition to the complex multisystem autoimmune phenomenon, other variable factors may also be implicated in the etiopathogenesis of this disease. Also, if a patient presents with subacute vision loss and an acute onset headache and encephalopathy, this differential diagnosis should be kept in mind, and the patient should be treated as soon as possible if the diagnosis is confirmed.
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Glucocorticoides/administração & dosagem , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Síndrome Uveomeningoencefálica/diagnóstico , Idoso , Diagnóstico Diferencial , Humanos , Masculino , Síndrome Uveomeningoencefálica/tratamento farmacológico , Transtornos da Visão/etiologiaRESUMO
Gaming and gambling have been studied in terms of similarity of its manifestations. There is a dearth of empirical-based evidence for the exploration of pathways to understand the shift from gaming to gambling. A 23-year-old male from a nuclear family was assessed using clinical interview for the pathways for shifting from gaming to gambling. The pathways were personality predispositions, maladaptive coping, interpersonal distress, peer pressure, variable reward anticipation, addiction characteristics in the form of craving, loss of control and use despite having consequences. These findings suggest that there is a need to create awareness among young adults about these potential causes related to transition from gaming to gambling.
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INTRODUCTION: The temporo-mandibular joint (TMJ) is a complex anatomical structure that is concerned with mastication, deglutition, and speech. Ankylosis of the TMJ occurs when the condyle gets fused to glenoid fossa by bony or fibrous tissue. It is an incapacitating problem, commonly occurring in children and is usually associated with trauma or infection. MATERIALS AND METHODS: A total of ten patients with written informed consent having TMJ ankylosis (unilateral/bilateral) fulfilling the inclusion criteria were selected for the study and were operated under general anaesthesia with arthrectomy followed by reconstruction of ramal condylar unit with SCG (Group I) or CCG (Group II). Pre-operative and post-operative evaluation assessments were done at regular intervals for maximum mouth opening, range of mandibular movements, and height of ramus. RESULTS: Statistical analysis shows that the increase in maximum mouth opening was found 1.1% higher in Group II (75.9%) as compared to Group I (74.9%). The increase in lateral excursion at affected side was found 1.3% higher in Group I (84.6%) as compared to Group II (83.3%). The increase in lateral excursion at non-affected side was found 10.3% higher in Group I (76.9%) as compared to Group II (66.7%). The increase in protrusive movement was found 17.5% higher in Group II (88.9%) as compared to Group I (71.4%). Six months post-operative height of ramus was found 10.5% higher in Group II as compared to Group I. CONCLUSION: The present study concludes the superiority of costochondral graft over sternoclavicular graft in terms of growth and function. Continued deliberation between the two grafts with larger sample size and a longer follow-up with multicentric consensus will be required to draw definitive indications of the two grafts.
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Coccydynia in adult patients is not uncommon and is frequently neglected. Coccydynia is mostly associated with fall on buttocks. In long-standing cases, coccydynia can be debilitating. Rarely coccydynia can be due to more sinister causes and surgeons should be aware of all differential diagnosis. We present a case of an elderly female who presented with a complaint of pain over coccyx which was not subsiding with conventional treatment methods. Biopsy was done and a diagnosis of sclerosing epitheloid fibrosarcoma was made. We describe an unusual case of coccydynia secondary to this tumour with the histopathology finding and surgical management.
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Ca2+ plays an important role in the physiology of bacteria. Intracellular Ca2+ concentrations are tightly maintained in the nanomolar range. Molecular mechanisms of Ca2+ uptake in bacteria remain elusive. Here we show that CtpE is responsible for Ca2+ uptake in Mycobacterium smegmatis It represents a previously uncharacterized P-type ATPase family in bacteria. Disruption of ctpE in M. smegmatis resulted in a mutant with impaired growth under Ca2+-deficient conditions. The growth defect of the mutant could be rescued by Ca2+ or by ectopic expression of ctpE from M. smegmatis or the orthologous gene (Rv0908) from Mycobacterium tuberculosis H37Rv. Radioactive transport assays revealed that CtpE is a Ca2+-specific transporter. Ca2+ deficiency increased expression of ctpE, resulting in increased 45Ca2+ accumulation in cells. ctpE is a gene that is part of an operon, which is negatively regulated by Ca2+ The ctpE mutant also showed hypersensitivity to polymyxin B, increased biofilm formation, and higher cell aggregation, indicating cell envelope defects. Our work establishes, for the first time, the presence of Ca2+ uptake pumps of the energy-dependent P-type ATPase superfamily in bacteria and also implicates that intracellular Ca2+ is essential for growth and cell envelope integrity in M. smegmatisIMPORTANCE Ca2+ is essential for gene regulation, enzymatic activity, and maintenance of structural integrity of cell walls in bacteria. Bacteria maintain intracellular calcium concentrations in a narrow range, creating a gradient with low cytoplasmic calcium concentration and high extracellular calcium concentration. Due to this steep gradient, active pumps belonging to family 2 of P-type ATPases and antiporters are used for Ca2+ efflux, whereas Ca2+ uptake is usually carried out by channels. Molecular mechanisms of Ca2+ uptake in bacteria are still elusive and are mainly limited to a nonproteinaceous channel in Escherichia coli and a pH-dependent channel protein from Bacillus subtilis Energy-dependent active transporters are not reported for Ca2+ uptake from any organism. Here we show that CtpE belonging to a family of previously uncharacterized bacterial P-type ATPases is involved in specific uptake of Ca2+ into Mycobacterium smegmatis We also demonstrate that intracellular Ca2+ obtained through CtpE is essential for growth and maintenance of cell surface properties under Ca2+-deficient conditions.
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Cálcio/metabolismo , Mycobacterium smegmatis/metabolismo , ATPases do Tipo-P/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Transporte Biológico , Membrana Celular/fisiologia , Regulação Bacteriana da Expressão Gênica , Proteínas de Membrana Transportadoras/metabolismo , Mycobacterium smegmatis/genética , Mycobacterium smegmatis/crescimento & desenvolvimento , Mycobacterium tuberculosis/genética , Óperon , ATPases do Tipo-P/genéticaRESUMO
OBJECTIVE: To present the clinical, lab profile and outcome of a series of six children who had features of meningoencephalitis (median age of 10.5 y) diagnosed as confirmed scrub typhus (ST) by using a lgM ELISA commercial kit (InBiOS International Inc. USA). METHODS: This was a prospective observational study conducted at a tertiary care hospital, over a period of 7 mo through April 2014. All the patients with undifferentiated febrile illness (aged 1-18 y) with fever of 5-21 d duration were evaluated. After thorough physical examination they were subjected to blood investigations such as complete blood count (CBC), blood culture, hepatic and kidney function tests, serum electrolytes, cerebrospinal fluid (CSF) analysis and IgM ELISA for scrub typhus, coagulogram and chest radiograph, wherever indicated. RESULTS: During this period, of the total 81 confirmed cases based on a positive scrub IgM ELISA and/or eschar, 6 (7.4 %), had neurological involvement in the form of presence of neck stiffness, altered sensorium and/or seizures and the CSF findings were suggestive of meningoencephalitis and all had evidence of multiple organ dysfunction syndrome (MODS) needing intensive care. The CECT could be performed in four patients only showing evidence of effacement of sulci and evidence of brain edema. CONCLUSIONS: This communication highlights that variable central nervous system (CNS) involvement is not uncommon in patients with scrub typhus with high mortality. CSF and neuro-radiology findings are nonspecific as these are also observed in patients with aseptic meningitis or encephalitis. Early suspection and institution of appropriate therapy without delay will lead to substantial reduction in the morbidity and mortality.