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When using amikacin to treat Mycobacterium avium complex pulmonary disease (MAC-PD), a minimum inhibitory concentration resistance breakpoint of ≥64 mcg/mL is recommended. We explored whether amikacin resistance characterized by phenotypic drug susceptibility testing was associated with clinical outcomes or mutational resistance in a retrospective cohort of patients with MAC-PD. Despite little aminoglycoside exposure, amikacin resistance was common in our MAC-PD patients but was not associated with worse outcomes or rrs gene mutations.
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The uncontrolled growth and spread of cancerous cells beyond their usual boundaries into surrounding tissues characterizes cancer. In developed countries, cancer is the leading cause of death, while in underdeveloped nations, it ranks second. Using existing cancer diagnostic tools has increased early detection rates, which is crucial for effective cancer treatment. In recent decades, there has been significant progress in cancer-specific survival rates owing to advances in cancer detection and treatment. The ability to accurately identify precursor lesions is a crucial aspect of effective cancer screening programs, as it enables early treatment initiation, leading to lower long-term incidence of invasive cancer and improved overall prognosis. However, these diagnostic methods have limitations, such as high costs and technical challenges, which can make accurate diagnosis of certain deep-seated tumors difficult. To achieve accurate cancer diagnosis and prognosis, it is essential to continue developing cutting-edge technologies in molecular biology and cancer imaging.
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Detecção Precoce de Câncer , Neoplasias , Humanos , Detecção Precoce de Câncer/métodos , Neoplasias/diagnóstico , Neoplasias/terapia , Neoplasias/genética , Prognóstico , Biomarcadores Tumorais/genética , Resultado do TratamentoRESUMO
KEY MESSAGE: Mapping and fine mapping of bean anthracnose resistance genes is a continuous process. We report fine mapping of anthracnose resistance gene Co-18 which is the first anthracnose gene mapped to Pv10. The discovery of resistance gene is a major gain in the bean anthracnose pathosystem research. Among the Indian common bean landraces, KRC-5 exhibit high levels of resistance to the bean anthracnose pathogen Colletotrichum lindemuthianum. To precisely map the anthracnose resistance gene, we used a Recombinant Inbred Line (F2:9 RIL) population (KRC-5 × Jawala). The inheritance test revealed that KRC-5 carries a dominant resistance gene temporarily designated as Co-18. We discovered two RAPD markers linked to Co-18 among 287 RAPD markers. These RAPD markers were eventually developed into SCARs (Sc-OPR15 and Sc-OPF6) and flank Co-18 on chromosome Pv10 at a distance of 5.3 and 4.2 cM, respectively. At 4.0-4.1 Mb on Pv10, we detected a SNP (single-nucleotide polymorphism) signal. We synthesized 58 SSRs and 83 InDels from a pool of 135 SSRs and 1134 InDels, respectively. Five SSRs, four InDels, and two SCARs were used to generate the high-density linkage map, which led to the identification of two SSRs (SSR24 and SSR36) that are tightly linked to Co-18. These two SSRs flank the Co-18 to 178 kb genomic region with 13 candidate genes including five NLR (nucleotide-binding and leucine-rich repeat) genes. The closely linked markers SSR24 and SSR36 will be used in cloning and pyramiding of the Co-18 gene with other R genes to develop durable resistant bean varieties.
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Phaseolus , Phaseolus/genética , Cicatriz , Técnica de Amplificação ao Acaso de DNA Polimórfico , Mapeamento Cromossômico , Genes DominantesRESUMO
Microproteins, known as micropeptides, are small protein molecules encoded by short open reading frames. These recently identified molecules have been proven to be an essential part of the human proteome that participates in multiple processes, such as DNA repair, mitochondrial respiration, and regulating different signaling pathways. A growing body of studies has evidenced that microproteins exhibit dysregulated expression levels in various malignancies and contribute to tumor progression. It has been reported that microproteins interact with many proteins, such as enzymes (e.g., adenosine triphosphate synthase) and signal transducers (e.g., c-Jun), and regulate malignant cell metabolism, proliferation, and metastasis. Moreover, microproteins have been found to play a significant role in multidrug resistance in vitro and in vivo by their activity in DNA repair pathways. Considering that, this review intended to summarize the roles of microproteins in different aspects of tumorigenesis with diagnostic and therapeutic perspectives.
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Progressão da Doença , Neoplasias , Humanos , Neoplasias/metabolismo , Neoplasias/patologia , Carcinogênese/metabolismo , Carcinogênese/patologia , Animais , Transdução de Sinais , Peptídeos/metabolismo , Reparo do DNA , MicropeptídeosRESUMO
BACKGROUND: Supratentorial intraventricular tumors, encompassing lateral and third ventricular tumors, are uncommon intracranial neoplasms, typically slow-growing and benign, manifesting symptoms only upon reaching a substantial size. This study aims to identify optimal surgical approaches, assess the prevalence and characteristics of these tumors, and evaluate postoperative outcomes among pediatric and adult age groups. METHODS: A retrospective comparative study at a tertiary care hospital from January 2014 to June 2020 included 165 patients (68 pediatrics, 97 adults) meeting inclusion criteria for intraventricular tumor management. Data covered demographic factors, clinical history, neurological assessments, neuroimaging, surgical approaches, histopathological diagnoses, immunohistochemical features, adjuvant therapies, follow-up status, postoperative complications, and morbidity/mortality. RESULTS: Ventricular tumor incidence showed male preponderance in both adults (M:F = 1.2:1) and pediatrics (M:F = 3:1). Lateral ventricles were the most common location. Pediatric cases exhibited more frequent calcifications on computed tomography scans (35.6% vs. 29.5%). Grade II and III tumors were more prevalent in adults within the lateral ventricle (27.1 and 1.9%) compared with pediatrics (6.5 and 8.4%). The third ventricle predominantly featured benign lesions, with pediatric patients experiencing significantly longer hospital stays (16.12 ± 21.94 days vs. 9.58 ± 6.21 days) (p = 0.006). Adults and pediatric patients showed a significant difference in high-grade lateral ventricle tumors (p-value = 0.002*). CONCLUSIONS: Supratentorial ventricular tumors are relatively more prevalent in children than adults, presenting challenges due to size and bleeding risks. Surgical resection is the primary treatment, with a focus on the optimal approach for gross total excision to reduce recurrence risk.
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PURPOSE: This study evaluates the efficacy of SISCOS (Subtraction ictal-interictal SPECT coregistered to SPECT) in localizing the epileptogenic zone (EZ) in focal cortical dysplasia (FCD), comparing its predictive performance with MRI and post-surgical outcomes based on ILAE classification. METHODS: 84 patients with drug refractory epilepsy (DRE) who were operated and had histopathology consistent with FCD, were included in the study. All patients had undergone a complete work-up including SISCOS and MRI for EZ localization, followed by discussion in the multidisciplinary epilepsy surgery meeting prior to surgery. Ictal & interictal perfusion SPECT studies were performed with Tc-99 m Ethylene Cysteinate Dimer (Tc-99 m ECD) followed by SISCOS analysis using SPM2 and Bioimage Suite 2.6. Concordance for localization was determined by comparing with the surgical resection site and post-surgical outcomes were assessed using the ILAE classification. RESULTS: The concordance for EZ localization demonstrated by SISCOS was 73.8% and MRI was 82.1%. 52 patients (61.9%) had good surgical outcome and 31(59%) of these were FCD type 2. In patients with discordant MRI findings, SISCOS was able to provide localisation in 86% (13/15), with 69.2% showing good surgical outcomes. Sensitivity of SISCOS and MRI was 73% (95% CI = 59-84.8%) and 78% (95% CI = 67.5-90.3%) respectively with no significant difference between the two. In FCD type I, both SISCOS and MRI revealed a similar a sensitivity of 76.4% (95%CI = 50.1-93.2%). Concordant cases exhibited higher seizure-free odds ratios for both modalities. CONCLUSION: SISCOS is effective in localizing the EZ in FCD patients, comparable to MRI. Integrating SISCOS and MRI enhances lesion detection, especially in MRI discordant cases. A comprehensive diagnostic approach utilizing SISCOS and MRI can optimize the non-invasive pre-surgical assessment in DRE thereby guiding surgical decision-making in a resource-limited setting.
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A 13-year-old female patient presented with painless vision loss and proptosis for 18 months. Imaging findings were highly suggestive of a supraorbital aneurysmal bone cyst (ABC) for which she underwent complete surgical excision. Postoperatively, she developed left hemiparesis. Computed tomography angiography (CTA) revealed right complete internal carotid arterial (ICA) thrombosis. This was managed conservatively, and she improved in hemiparesis over the next 3 weeks. Histopathology report revealed osteosarcoma with secondary ABC, for which she was referred for radiotherapy. At 1.5 months follow-up, the patient's left lower limb power improved to 4 + /5. She was walking without support, and her left upper limb power was 4/5.
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Cistos Ósseos Aneurismáticos , Neoplasias Ósseas , Osteossarcoma , Adolescente , Feminino , Humanos , Cistos Ósseos Aneurismáticos/complicações , Cistos Ósseos Aneurismáticos/diagnóstico por imagem , Cistos Ósseos Aneurismáticos/cirurgia , Neoplasias Ósseas/complicações , Angiografia por Tomografia Computadorizada , ParesiaRESUMO
BACKGROUND: Intracranial mesenchymal chondrosarcoma (IMC) is a rare malignant tumor in pediatric population. IMC can present as extra- or intra-axial lesion in pediatric patients, though the former is commoner causing raised intracranial pressure (ICP). Radiological diagnosis is a challenge in these cases, as is it difficult to differentiate these from other extra-axial neoplasms due to the wide differential diagnosis in pediatric population. We aim to systematically review the literature and present a rare case of extraskeletal intracranial mesenchymal chondrosarcoma treated with safe maximal resection. METHODS: A systematic review of literature was conducted in accordance with PRISMA guidelines. PubMed and Scopus databases were queried using the search terms, "primary intracranial chondrosarcoma", "extraskeletal mesenchymal chondrosarcoma", "mesenchymal chondrosarcoma" and "pediatric". Presentation, surgical management and outcome of a 15-year-old male with an extraskeletal IMC are also described. RESULTS: The search yielded 25 articles which met the inclusion criteria. These published records consisted of 33 IMC cases with mean age at presentation of 9.81 ± 5.2 years (range 2 months to 18 years). Frontal region was the commonest locations (11, 33.3%). Most common presentation was headache (14, 42.4%). All patients underwent surgical intervention: gross total resection (20, 60.6%), subtotal resection (9, 27.3%) and no extent mentioned (4, 12.1%). No adjuvant therapy was received in 15 patients (45.5%). On latest follow-up, 11 patients (33.3%) are on remission, 5 patients (15.2%) are symptom free, 3 patients (9.1%) had recurrence, 2 patients (6.1%) had metastasis and 9 patients (27.3%) expired. CONCLUSION: IMC is a rare entity in pediatric population with imaging findings which are non-characteristic leading to its diagnostic challenge. It can masquerade as other extra-axial intracranial neoplasm (meningioma or hemangiopericytoma). Combination of clinico-radiological and pathological examination can help in accurate diagnosis. Safe Maximal resection followed by radiotherapy is the preferred treatment strategy.
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Neoplasias Encefálicas , Condrossarcoma Mesenquimal , Humanos , Condrossarcoma Mesenquimal/cirurgia , Condrossarcoma Mesenquimal/diagnóstico por imagem , Condrossarcoma Mesenquimal/patologia , Criança , Adolescente , Masculino , Neoplasias Encefálicas/cirurgia , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Lactente , Pré-EscolarRESUMO
Chemical weathering processes are becoming increasingly important in studies on carbon cycling because they are responsible for increased solute fluxes in the proglacial zone, can effectively sequester atmospheric CO2 and raise carbon budgets for lateral transport via rivers. Here, we examined the hydrochemical and hydrogeochemical processes, solute sources and factors controlling riverine pCO2 of the Alaknanda River and its tributaries for three sampling seasons, viz. pre-monsoon (May 2021), post-monsoon (October 2021) and winter (January 2022). The surface water is enriched with Ca2+ and Mg2+ as the dominant cations, while HCO3- and SO42- were the major anions. Gibbs's plot confirmed rock weathering as the leading mechanism in controlling the hydrochemistry of the basin. The chemical composition of river water was mainly regulated by the weathering of carbonate end members: dolomite, limestone and feldspar along with small inputs from silicate weathering. The mean pCO2 values in the mainstream (1702.7 µatm), Pindar (2267.9 µatm) and Mandakini (1136.1 µatm) revealed the streams were oversaturated with CO2 having a higher rate of exporting excess CO2 gas to the atmosphere. The study showed the persistence of high pCO2 closed system characteristics associated with increased suspended sediment concentration resulting from carbonate weathering, dominance of HCO3- over SO42- and thereby results in high values of C ratio. Principal component analysis of the water chemistry suggests that weathering contributes about 41%, while humans contribute about 13% of the ionic load to the river. This study is one of its kind to understand the system characteristics of Alaknanda River water.
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Dióxido de Carbono , Monitoramento Ambiental , Rios , Poluentes Químicos da Água , Rios/química , Dióxido de Carbono/análise , Poluentes Químicos da Água/análise , Índia , Estações do Ano , Ciclo do CarbonoRESUMO
A 25-year-old woman presented with 1 year of progressive orthopnoea, initially explained as bilateral diaphragmatic paresis caused by seronegative myasthenia gravis. She required assisted ventilation and received pyridostigmine and corticosteroids. She had minimal (particularly proximal) symmetrical tetraparesis with apparent bilateral diaphragmatic weakness, but had normal sensation. Further investigation suggested an overlap myositis with shrinking lung syndrome from systemic lupus erythematosus. She improved following immunosuppression with pulse corticosteroids and rituximab, and at 3 months no longer needed bilevel positive airway pressure support.
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Lúpus Eritematoso Sistêmico , Paralisia Respiratória , Humanos , Feminino , Adulto , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico , Paralisia Respiratória/etiologia , Paralisia Respiratória/diagnóstico , Diagnóstico Diferencial , Pneumopatias/etiologia , Pneumopatias/diagnósticoRESUMO
Acute haemorrhagic pancreatitis is a medical emergency and the most severe form of Acute Pancreatitis. It is characterized by severe epigastric pain that radiates to the back and is associated with vomiting. If not diagnosed and managed promptly, it may result in sudden, unexpected, unexplained deaths which fall within the medicolegal domain. In such cases, the role of an autopsy is of paramount importance to determine the cause of death. Here we report a young adult, who presented to the local hospital with vague abdominal discomfort and vomiting following alcohol intake and referred to our tertiary care center for further management. But he was received dead on arrival at our hospital. The diagnosis of acute haemorrhagic pancreatitis was made only after the post mortem examination. Awareness of the physicians about the unusual symptoms in acute haemorrhagic pancreatitis and the need for pancreas examination at autopsy of all sudden deaths is emphasised.
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Pancreatite , Humanos , Masculino , Evolução Fatal , Pancreatite/diagnóstico , Adulto , Autopsia , Doença Aguda , Adulto Jovem , Hemorragia/diagnóstico , Hemorragia/etiologiaRESUMO
BACKGROUND: Although clozapine is the most efficacious medication for treatment-refractory schizophrenia, not all patients will have an adequate response. Optimising clozapine dose using therapeutic drug monitoring could therefore maximise response. AIMS: Using individual patient data, we undertook a receiver operating characteristic (ROC) curve analysis to determine an optimal therapeutic range for clozapine levels to guide clinical practice. METHOD: We conducted a systematic review of PubMed, PsycINFO and Embase for studies that provided individual participant level data on clozapine levels and response. These data were analysed using ROC curves to determine the prediction performance of plasma clozapine levels for treatment response. RESULTS: We included data on 294 individual participants from nine studies. ROC analysis yielded an area under the curve of 0.612. The clozapine level at the point of optimal diagnostic benefit was 372 ng/mL; at this level, the response sensitivity was 57.3%, and specificity 65.7%. The interquartile range for treatment response was 223-558 ng/mL. There was no improvement in ROC performance with mixed models including patient gender, age or length of trial. Clozapine dose and clozapine concentration to dose ratio did not provide significantly meaningful prediction of response to clozapine. CONCLUSIONS: Clozapine dose should be optimised based on clozapine therapeutic levels. We found that a range between 250 and 550 ng/mL could be recommended, while noting that a level of >350 ng/mL is the most optimal for response. Although some patients may not respond without clozapine levels >550 ng/mL, the benefits should be weighed against the increased risk of adverse drug reactions.
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Antipsicóticos , Clozapina , Esquizofrenia , Humanos , Clozapina/uso terapêutico , Antipsicóticos/uso terapêutico , Curva ROC , Esquizofrenia/diagnóstico , Escalas de Graduação PsiquiátricaRESUMO
INTRODUCTION: Intracranial myeloid sarcoma is a rare extramedullary presentation of acute myeloid leukemia (AML). It can involve the meninges and ependyma presenting as extra-axial mass lesion. Rarely, it can also invade the brain parenchyma. It is commonly seen in children. It is usually misdiagnosed due to its close resemblance to other intracranial tumors (meningioma, metastasis, Ewing's sarcomas, and lymphoma). These are underdiagnosed if they precede the diagnosis of leukemia. CASE REPORT: A 7-year-old boy with isolated intracranial myeloid sarcoma who presented with raised intracranial pressure (ICP) which was successfully managed by surgical excision. CONCLUSION: Isolated intracranial myeloid sarcoma is a rare presentation of AML. Leukemia can be diagnosed early during the postoperative period and can be started on therapy timely. These patients requires regular follow-ups (clinical, laboratory and radiological) to detect relapses early.
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Neoplasias Encefálicas , Leucemia Mieloide Aguda , Neoplasias Meníngeas , Sarcoma de Ewing , Sarcoma Mieloide , Masculino , Criança , Humanos , Sarcoma Mieloide/diagnóstico por imagem , Sarcoma Mieloide/cirurgia , Leucemia Mieloide Aguda/diagnóstico por imagem , Leucemia Mieloide Aguda/patologia , Neoplasias Meníngeas/diagnóstico , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/cirurgiaRESUMO
Mesenteric vascular thrombosis, typically of the superior mesenteric artery, is a frequent occurrence in patients with hypercoagulable conditions. Isolated involvement of the celiac artery is rare. Patients with celiac artery thrombosis can present with an acute abdomen or occasionally with acid peptic symptoms. A delay in diagnosis is associated with high rates of morbidity and mortality. We present a rare case of splenic infarction with celiac trunk thrombosis in a 54-year-old patient with underlying antiphospholipid (APLA) syndrome who presented with epigastric pain that was mistaken for symptoms of acid reflux.
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Abdome Agudo , Trombose , Humanos , Pessoa de Meia-Idade , Artéria Celíaca/diagnóstico por imagem , Abdome Agudo/etiologia , Artéria Mesentérica Superior/diagnóstico por imagem , Trombose/diagnóstico por imagem , Dor Abdominal/etiologiaRESUMO
Aims: The aim of this study was to compare the immediate and long-term outcomes after high spermatic vessel ligation (HSVL) and low spermatic vessel ligation (LSVL) in a high undescended testis (UDT) model in rats. Materials and Methods: A prospective randomized controlled study was conducted on 24 male Wistar rats. The rats were randomly divided into three groups. Group A underwent a sham laparotomy and acted as the control. Group B underwent HSVL of both testicular vessels. Group C underwent LSVL of both testicular vessels. Each group was again subdivided into two subgroups. One sub-group underwent blood collection and testicular biopsy of both testes 24 h after the procedure to demonstrate immediate changes. Other subgroups underwent blood sample collection and testicular biopsy of both testes on day 50 following the procedure for hormonal changes and long-term changes. Results: All the testes in HSVL showed atrophy (100%) in the long term, whereas LSVL showed atrophy in 12.5% of testes, even though both groups showed adequate neovascularization. Testes in HSVL showed poor bleeding on incision at both 24 h and day 50. On histology, 75% of testes in HSVL showed complete necrosis, and 50% in LSVL showed partial necrosis at 24 h. On day 50, all the testes in HSVL (100%) showed complete necrosis with dystrophic calcification, whereas all the testes in LSVL showed normal histology with good maturation of seminiferous tubules. There was no significant difference in testosterone levels between both groups. Conclusions: Both immediate and long-term changes following LSVL showed an increase in blood flow to the testis after ligation through collaterals and reverses early ischemic changes to the testis. Given the higher testicular atrophic rate after HSVL, LSVL or at least low ligation can be preferred for the management of high intra-abdominal UDT.
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Background Traumatic brain injury (TBI) is a significant cause of disability and mortality globally. Information regarding clinical presentation and management of TBI patients in the district hospital settings is inadequate, especially in low- and middle-income countries. Objective This study aims to describe the demographic and clinical profiles of traumatic brain injury patients in a district hospital setting in Nepal. Method This study was done at Chautara Hospital in Sindhupalchowk district from December 2021 to June 2022. Sixty-one patients were included using non-probability sampling. The age and sex of patients, cause of injury, distance from the hospital, the severity of the injury based on the Glasgow Coma Scale, site of trauma on the head, and disposition of patients were analyzed. Result Sixty-one patients met the inclusion criteria out of which 29 were males and 32 were females. The mean age of the patients was 42.5 years. The most frequent cause was fall from height (23), and the most common injury site was the frontal region of the head (29). Most patients had a mild injury (52) followed by severe (five). Only two patients had moderate injury. Forty-two patients sustained injury within 5 kilometres of the hospital. Thirty patients were referred to higher centres for further treatment. Conclusion Falls from height is the most common cause of traumatic brain injury followed by road traffic accidents. As most of the cases are mild in severity, the availability of trained human resources and telemedicine consultation in district hospitals can substantially decrease referral to higher centres and therefore decrease the burden of traumatic brain injury patients in the higher centres.
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Lesões Encefálicas Traumáticas , Escala de Coma de Glasgow , Hospitais de Distrito , Humanos , Nepal/epidemiologia , Masculino , Lesões Encefálicas Traumáticas/epidemiologia , Lesões Encefálicas Traumáticas/terapia , Feminino , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Adolescente , Idoso , Acidentes por Quedas/estatística & dados numéricosRESUMO
Background The basic principles of research methodology are very important for the successful conduct of research. Objective To evaluate the knowledge and perceptions before and after a three-day workshop on health research methodologies conducted at a medical college in Lalitpur, Nepal. Method The pre-post study was conducted during the workshop. There were 31 participants comprising of doctors (interns and residents), medical officers and dental surgeons and faculties. A questionnaire containing two sections related to various themes of the workshop was developed to measure the respondents' knowledge and perception of different concepts. Feedback regarding each session was also obtained. The median knowledge and perception scores before and after the workshop were compared using appropriate statistical tests (p < 0.05). Result More than half of the participants, [18 (58.1%)] were of 20-30 years of age. The total knowledge scores improved significantly after the workshop. The increase in the perception scores after the workshop was also significant. Feedback was positive. The highest feedback score was for the session on critical analysis of a published article. Conclusion Knowledge and perceptions increased significantly indicating such workshops can be effective and contribute to the capacity building of the early-stage researchers.
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Pesquisa Biomédica , Humanos , Nepal , Adulto , Masculino , Feminino , Inquéritos e Questionários , Adulto Jovem , Conhecimentos, Atitudes e Prática em SaúdeRESUMO
Histone deacetylases (HDACs) have been described to have both neurotoxic and neuroprotective roles, and partly, depend on its sub-cellular distribution. HDAC inhibitors have a long history of use in the treatment of various neurological disorders including epilepsy. Key role of HDACs in GABAergic neurotransmission, synaptogenesis, synaptic plasticity and memory formation was demonstrated whereas very less is known about their role in drug-resistant epilepsy pathologies. The present study was aimed to investigate the changes in the expression of HDACs, activity and its sub-cellular distribution in mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) patients. For this study, surgically resected hippocampal tissue specimens of 28 MTLE-HS patients and 20 hippocampus from post-mortem cases were obtained. Real-time PCR was done to analyse the mRNA expression. HDAC activity and the protein levels of HDACs in cytoplasm as well as nucleus were measured spectrophotometrically. Further, sub-cellular localization of HDACs was characterized by immunofluorescence. Significant upregulation of HDAC1, HDAC2, HDAC4, HDAC5, HDAC6, HDAC10 and HDAC11 mRNA were observed in MTLE-HS. Alterations in the mRNA expression of glutamate and gamma-aminobutyric acid (GABA) receptor subunits have been also demonstrated. We observed significant increase of HDAC activity and nuclear level of HDAC1, HDAC2, HDAC5 and HDAC11 in the hippocampal samples obtained from patients with MTLE-HS. Moreover, we found altered cytoplasmic level of HDAC4, HDAC6 and HDAC10 in the hippocampal sample obtained from patients with MTLE-HS. Alterations in the level of HDACs could potentially be part of a dynamic transcription regulation associated with MTLE-HS. Changes in cytoplasmic level of HDAC4, 6 and 10 suggest that cytoplasmic substrates may play a crucial role in the pathophysiology of MTLE-HS. Knowledge regarding expression pattern and sub-cellular distribution of HDACs may help to devise specific HDACi therapy for epilepsy.
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Epilepsia do Lobo Temporal , Epilepsia , Epilepsia/patologia , Epilepsia do Lobo Temporal/metabolismo , Hipocampo/metabolismo , Histona Desacetilases/metabolismo , Humanos , Imageamento por Ressonância Magnética , Esclerose/patologiaRESUMO
PURPOSE: Calcium sensing receptor (CaSR), on the surface of normal parathyroid cells, is essential for maintaining serum calcium levels. The normal pattern of CaSR immunostaining remains undefined and is presumptively circumferential. Given the physiological variation in serum calcium, we postulated that CaSR expression could not be uniformly circumferential. Also, cytoplasmic expression has not been evaluated either in normal or pathological tissues. We studied normal parathyroid tissues derived from forensic autopsies and those rimming parathyroid adenomas for membranous and cytoplasmic CaSR immunoexpression. Results were compared with primary hyperparathyroidism (PHPT) to look for any pathogenetic implications. MATERIALS AND METHODS: We evaluated 34 normal parathyroid tissues from 11 autopsies, 30 normal rims, 45 parathyroid adenoma, 10 hyperplasia, and 7 carcinoma cases. Membranous expression was categorized complete/incomplete and weak/moderate/strong; scored using Her2/Neu and Histo-scores; predominant pattern noted. Cytoplasmic expression was categorized negative/weak/moderate/strong; predominant intensity noted. RESULTS: Normal autopsy-derived parathyroid tissues were Her2/Neu 3 + , but incomplete membranous staining predominated in 85%. Their immune-scores were significantly more than the cases (p < < 0.05). The mean histo-score of normal rims was intermediate between the two (p < < 0.05). Cytoplasmic expression was strong in all autopsy-derived tissues, weak/negative in hyperplasia (100%), moderate in 16% adenomas, and 43% carcinomas. CONCLUSIONS: Normal autopsy-derived parathyroid tissues showed strong but predominantly incomplete membranous expression. Surface CaSR expression decreased in PHPT and is probably an early event in parathyroid adenoma, seen even in normal rims. Whether there is a defect in CaSR trafficking from the cytoplasm to the cell surface in adenoma and carcinoma needs further evaluation.
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Hiperparatireoidismo Primário , Glândulas Paratireoides , Neoplasias das Paratireoides , Receptores de Detecção de Cálcio/análise , Adulto , Autopsia , Feminino , Perfilação da Expressão Gênica/métodos , Humanos , Hiperparatireoidismo Primário/metabolismo , Hiperparatireoidismo Primário/patologia , Imuno-Histoquímica , Técnicas Imunológicas/métodos , Proteínas Sensoras de Cálcio Intracelular/metabolismo , Masculino , Glândulas Paratireoides/metabolismo , Glândulas Paratireoides/patologia , Neoplasias das Paratireoides/metabolismo , Neoplasias das Paratireoides/patologiaRESUMO
Hypoglycemia presents with a spectrum of neurological manifestations ranging from lightheadedness to confusion and coma. We report here the case of a 61-year-old woman with right hemiparesis presenting within the window period for stroke thrombolysis. MRI brain showed diffusion restriction in posterior limb of left internal capsule and splenium. Patient had documented hypoglycemia of 38 mg/dL. Patient's hemiparesis resolved after glucose correction, and radiological findings completely resolved after 10 days. We present this case to highlight the rare radiological finding of simultaneous internal capsule and splenium involvement in hypoglycemic hemiparesis and the importance to rule out stroke mimics to avoid unwanted thrombolysis.