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1.
Can. j. cardiol ; 36(12): 1847-1948, Dec. 1, 2020.
Artigo em Inglês | BIGG - guias GRADE | ID: biblio-1146651

RESUMO

The Canadian Cardiovascular Society (CCS) atrial fibrillation (AF) guidelines program was developed to aid clinicians in the management of these complex patients, as well as to provide direction to policy makers and health care systems regarding related issues. The most recent comprehensive CCS AF guidelines update was published in 2010. Since then, periodic updates were published dealing with rapidly changing areas. However, since 2010 a large number of developments had accumulated in a wide range of areas, motivating the committee to complete a thorough guideline review. The 2020 iteration of the CCS AF guidelines represents a comprehensive renewal that integrates, updates, and replaces the past decade of guidelines, recommendations, and practical tips. It is intended to be used by practicing clinicians across all disciplines who care for patients with AF. The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) system was used to evaluate recommendation strength and the quality of evidence. Areas of focus include: AF classification and definitions, epidemiology, pathophysiology, clinical evaluation, screening and opportunistic AF detection, detection and management of modifiable risk factors, integrated approach to AF management, stroke prevention, arrhythmia management, sex differences, and AF in special populations. Extensive use is made of tables and figures to synthesize important material and present key concepts. This document should be an important aid for knowledge translation and a tool to help improve clinical management of this important and challenging arrhythmia.


Le programme de lignes directrices de la Société canadienne de cardiologie (SCC) en matière de fibrillation auriculaire (FA) a été élaboré pour aider les cliniciens à prendre en charge ces patients complexes, ainsi que pour orienter les décideurs politiques et les systèmes de soins de santé sur des questions connexes. La dernière édition complète des lignes directrices de la SCC en matière de FA a été publiée en 2010. Depuis lors, des mises à jour périodiques ont été publiées, traitant de domaines en évolution rapide. Cependant, en 2020, un grand nombre de développements s'y étaient ajoutés, couvrant un large éventail de domaines, ce qui a motivé le comité à créer une refonte complète des lignes directrices. L'édition 2020 des lignes directrices de la SCC en matière de FA représente un renouvellement complet qui intègre, met à jour et remplace les lignes directrices, les recommandations et les conseils pratiques des dix dernières années. Elle est destinée à être utilisée par les cliniciens praticiens de toutes les disciplines qui s'occupent de patients souffrant de FA. L'approche GRADE (Gradation des Recommandations, de l'Appréciation, du Développement et des Évaluations) a été utilisée pour évaluer la pertinence des recommandations et la qualité des résultats. Les domaines d'intérêt incluent : la classification et les définitions de la FA, son épidémiologie, sa physiopathologie, l'évaluation clinique, le dépistage de la FA, la détection et la gestion des facteurs de risque modifiables, l'approche intégrée de la gestion de la FA, la prévention des accidents vasculaires cérébraux, la gestion de l'arythmie, les différences entre les sexes et la FA dans des populations particulières. Des tableaux et figures ont été largement utilisés pour synthétiser les éléments importants et présenter les concepts clés. Ce document devrait représenter une aide importante pour l'intégration des connaissances et un outil pour aider à améliorer la gestion clinique de cette arythmie importante et difficile à traiter.


Assuntos
Humanos , Masculino , Feminino , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/terapia , Fibrilação Atrial/classificação , Fibrilação Atrial/fisiopatologia , Fibrilação Atrial/epidemiologia , Grupos de Risco , Algoritmos , Fatores Sexuais , Fatores de Risco , Procedimentos Clínicos , Acidente Vascular Cerebral/prevenção & controle
2.
Eur Rev Med Pharmacol Sci ; 24(23): 12593-12608, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33336780

RESUMO

The coronavirus disease 2019 (COVID-19) is declared as an international emergency in 2020. Its prevalence and fatality rate are rapidly increasing but the medication options are still limited for this perilous disease. The emergent outbreak of COVID-19 triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) keeps propagating globally. The present scenario has emphasized the requirement for therapeutic opportunities to relive and overcome this latest pandemic. Despite the fact, the deteriorating developments of COVID-19, there is no drug certified to have considerable effects in the medical treatment for COVID-19 patients. The COVID-19 pandemic requests for the rapid testing of new treatment approaches. Based on the evidence, hydroxychloroquine is the first medicine opted for the treatment of disease. Umifenovir, remdesivir, and fevipiravir are deemed the most hopeful antiviral agent by improving the health of infected patients. The dexamethasone is a first known steroid medicine that can save the lives of seriously ill patients, and it is shown in a randomized clinical trial by the United Kingdom that it reduced the death rate in COVID-19 patients. The current review recapitulates the existing evidence of possible therapeutic drugs, peptides, humanized antibodies, convulsant plasma, and vaccination that has revealed potential in fighting COVID-19 infections. Many randomized and controlled clinical trials are taking place to further validate these agent's safety and effectiveness in curing COVID-19.


Assuntos
Anti-Inflamatórios/uso terapêutico , Antivirais/uso terapêutico , /tratamento farmacológico , /terapia , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/uso terapêutico , Alanina/análogos & derivados , Alanina/uso terapêutico , Amidas/uso terapêutico , Antibacterianos/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Neutralizantes/uso terapêutico , Antiparasitários/uso terapêutico , Canabinoides/uso terapêutico , Cloroquina/uso terapêutico , Inativadores do Complemento/uso terapêutico , Dexametasona/uso terapêutico , Combinação de Medicamentos , Inibidores Enzimáticos/uso terapêutico , Humanos , Hidroxicloroquina/uso terapêutico , Imunização Passiva , Indóis/uso terapêutico , Interferons/uso terapêutico , Ivermectina/uso terapêutico , Lopinavir/uso terapêutico , Pirazinas/uso terapêutico , Ritonavir/uso terapêutico , Teicoplanina/uso terapêutico , Tetraciclinas/uso terapêutico , Tiazóis/uso terapêutico
3.
J Cancer Res Ther ; 16(6): 1314-1322, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33342790

RESUMO

Background: Role of hypofractionated radiotherapy (HFRT) in early breast cancer is established; comparatively, there are limited data for HFRT in locally advanced breast cancer (LABC). We report the impact of HFRT in unselected breast cancer patients in comparison with historically treated patients with conventional fractionated radiotherapy (CFRT). Patients and Methods: Records of 463 breast cancer patients treated between January 09 and July 13 with CFRT (50 Gy/25 fr) or HFRT (42.4 Gy in 16 fractions or 40 Gy in 15 fractions) in two sequential periods were retrospectively reviewed. The analysis was done in August 2018. The primary endpoint was to compare the differences in locoregional recurrence rate. Results: Of the 463 patients, 209 received CFRT and 254 received HFRT. The median age was 48 years (interquartile range: 40-56), premenopausal (CFRT: 23% vs. HFRT 39%, P = 0.005). The most common pathology was infiltrating ductal carcinoma (81%) with Grade III tumors (45%), estrogen receptor (+) was seen in 44%, triple-negative breast cancer in 34%, and Her2Neu (3+) were seen in 27%. Two hundred and fifty-four patients (54.5%) had undergone breast-conserving surgery (BCS) and 209 patients (45%) modified radical mastectomy (MRM). Nodal radiotherapy was delivered in 76% versus 64% in patients receiving CFRT versus HFRT, respectively (P = 0.005). With a median follow-up of 46 months in CFRT and 57 months in HFRT, 9/209 (4.3%) patients in CFRT and 7/254 (2.7%) in HFRT had locoregional relapse (LRR). The 4 years#39; actuarial local recurrence-free survival (LRFS) in CFRT versus HFRT was 95% versus 97% (P = 0.37). The mean estimated LRFS (local relapse-free survival) for CFRT is 113.4 months and for HFRT 94.2 months (P = 0.3). Conclusions: The risk of local recurrence among patients of breast cancer treated with HFRT after BCS or MRM was not worse when compared to CFRT.


Assuntos
Neoplasias da Mama/radioterapia , Recidiva Local de Neoplasia/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/patologia , Intervalo Livre de Doença , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Hipofracionamento da Dose de Radiação , Estudos Retrospectivos , Taxa de Sobrevida , Centros de Atenção Terciária , Adulto Jovem
4.
Br J Surg ; 107(11): e525, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32835420
5.
Biochim Biophys Acta Biomembr ; 1862(11): 183435, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32777224

RESUMO

Hsp70: J-domain protein (JDP) machines, along with the cellular protein degradation systems play a central role in regulating cellular proteostasis. An equally robust surveillance system operates at the plasma membrane too that affects proper sorting, stability as well as the turnover of membrane proteins. Although plausible, a definitive role of the Hsp70: JDP machine in regulating the stability of plasma membrane proteins is not well understood in Saccharomyces cerevisiae. Here we show that a moderate over-expression of Caj1, one of the thirteen JDPs residing in the nucleo-cytosolic compartment of S. cerevisiae reduced the cold sensitivity of tryptophan auxotrophic yeast cells by stabilizing tryptophan permeases, Tat1 and Tat2 in a J-domain dependent manner. Concomitantly, higher Caj1 levels also caused slow growth and increased plasma membrane damage at elevated temperatures possibly due to the stabilization of thermolabile plasma membrane proteins. Finally, we show that although majorly cytosolic, Caj1 also co-localizes with the membrane dye FM4-64 at the cellular periphery suggesting that Caj1 might interact with the plasma membrane. Based on the results presented in this study, we implicate the Hsp70: Caj1 chaperone machine in regulating the stability or turnover of plasma membrane proteins in budding yeast.

6.
Rev Sci Instrum ; 91(4): 044701, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32357711

RESUMO

Conventional thermionic microwave and radio frequency (RF) guns can offer high average beam current, which is important for synchrotron light and terahertz (THz) radiation source facilities, as well as for industrial applications. For example, the Advanced Photon Source at Argonne National Laboratory is a national synchrotron-radiation light source research facility that utilizes thermionic RF guns. However, these existing thermionic guns are bulky, difficult to handle and install, easily detuned, very sensitive to thermal expansion, and due for a major upgrade and replacement. In this paper, we present the design of a new, more stable, and reliable gun with optimized electromagnetic performance, improved thermal engineering, and a more robust cathode mounting technique, which is a critical step to improve the performance of existing and future light sources, industrial accelerators, and electron beam-driven THz sources. We will also present a fabricated gun prototype and show results of high-power and beam tests.

7.
Artigo em Inglês | MEDLINE | ID: mdl-32286247

RESUMO

Introduction Mental ability of children represents functioning of brain in different aspects of competency including verbal, mathematical, logical reasoning and spatial, which is of prime importance for academic performance. Objective The objective of this study was to assess the effect of yoga on general mental ability of urban residential school children. Methods Sixty-six urban school children aged 11-15 years were selected as participants. All the selected participants were staying in a residential school in Pune District. A stratified random sampling method was used to divide the students into experimental and control groups. There were 32 students in experimental group and 29 students in control group. Both experimental and control groups were assessed for general mental ability by using standard questionnaire at the baseline and at the end of 12 weeks of yoga training. The study participants of experimental group underwent yoga training for 12 weeks, for 1 h in the morning for a period of 12 weeks. The control group did not undergo any yoga training during this time period. Results The experimental group participants showed significant improvement in general mental ability as compared to control group. Conclusion The findings of this study indicate that yoga practices could improve general mental ability of urban residential school children.

8.
Domest Anim Endocrinol ; 72: 106371, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-31421986

RESUMO

High ambient temperature exhibits a retrograde effect on buffalo reproduction because of heat stress. Moreover, melatonin is known to regulate reproductive changes in seasonally reproductive animals by binding to high affinity, G protein-coupled receptors. The MTNR1A gene is a prime receptor, mediating the effect of melatonin at the neuroendocrine level to control seasonal reproduction. In sheep, the role of melatonin is well known; however, studies have not been conducted in buffalo to determine its effect during favorable and unfavorable breeding seasons. Therefore, the present study aimed to (1) determine the expression of MTNR1A, ERα, ERß, and PR gene transcripts in the ovarian follicles of buffalo during the summer and winter seasons and (2) analyze melatonin, 17ß-estradiol, and progesterone concentrations in the follicular fluid of buffalo during both seasons. Murrah buffalo ovaries were collected during both the summer (May-June) and winter (December-January) seasons. All visible ovarian follicles were allocated into one of three groups: (1) small (8-9.9 mm); (2) medium (10-11.9 mm); and (3) large (12-14 mm). Follicular fluid was aspirated from each group of follicles for hormone analyses. The granulosa cells were processed for RNA extraction. Furthermore, they were subjected to real-time quantitative PCR to analyze the expression (relative quantification) of MTNR1A, ERα, ERß, and PR in each follicular group. The expression of MTNR1A gene transcript decreased with the increasing size of the follicle and intrafollicular melatonin concentration. Expression of ERα and PR remained unaffected by the season and was similar (P > 0.05) in all groups. Expression of ERß was higher (P < 0.05) in summer than winter; nevertheless, small-sized follicles from the summer exhibited higher (P < 0.05) expressions than medium- and large-sized follicles. The overall intrafollicular melatonin concentration was positively correlated (P < 0.05) with 17ß-estradiol and progesterone concentrations. In conclusion, the decreased expression of MTNR1A and increased concentration of intrafollicular melatonin with the increasing size of the follicle indicates a probable role in folliculogenesis and ovulation in buffalo.

9.
Kathmandu Univ Med J (KUMJ) ; 18(70): 99-101, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33605247

RESUMO

Coronavirus disease 2019 (COVID-19) has become a pandemic disease globally. This extraordinary situation is posing an enormous burden on the healthcare systems worldwide and is reshaping the way in which chronic disorders are managed. Pandemic has made epilepsy care even more demanding in rural part of developing countries. We outline the adverse circumstances in epilepsy care induced by the pandemic; propose emergency management and follow up care of people with epilepsy. There is a requirement for public health systems in resource poor countries to improve awareness, implement proper strategies of triage, acute treatment, telemedicine services and virtual check-ins.


Assuntos
Epilepsia , Países em Desenvolvimento , Epilepsia/epidemiologia , Epilepsia/terapia , Humanos , Pandemias
10.
Artigo em Inglês | MEDLINE | ID: mdl-33579541

RESUMO

We designed this study to determine the efficiency and stability of anterior segmental osteotomies (ASO) without orthodontics for various dentofacial deformities. Records of patients treated with maxillary or mandibular ASO, or both, without orthodontics in the past 15 years were analysed. The assessment included postoperative analysis of patients' aesthetics and functional satisfaction using a questionnaire and grading (score 0 - 4) system, and the amount of relapse calculated from 12-month postoperative cephalograms. A total of 26 ASO subjects (age range 13- 31 years) were studied (14 maxillary, two mandibular, and 10 bimaxillary). Long-term stability was acceptable in all cases with no significant relapse (p>0.05). No major complications were encountered. All patients reported good to excellent (score=3 to 4) satisfaction following surgery. Using meticulous planning and a careful surgical technique, ASO without orthodontics is a simple, quick, safe, and stable option for the correction of dentofacial deformities.

11.
Br J Dermatol ; 181(6): e144, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31432498
12.
Vaccine ; 37(25): 3343-3351, 2019 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-31064674

RESUMO

The intracellular nature of Brucella leads to rise in oxidative stress due to bacterial invasion, particularly at the site of predilection spleen and lymph nodes. The present study aimed to evaluate the erythrocytic and tissue specific oxidative stress responses induced during oil adjuvant killed Brucella melitensis vaccination. The results of the study clearly implicated a significant increase in level of catalase, and superoxide dismutase (SOD) activity and lipid peroxidation (LPO), and total protein content in erythrocytes after vaccination. The activity of glutathione-S-transferase (GST) was unaltered during the period of experiment. The catalase activity and GSH content was significantly increased in lung and spleen tissues. The tissues GST levels increased significantly in all tissues, while tissue SOD level increased significantly only in lung tissues. Thus, it can be inferred that oil adjuvant based Brucella vaccine induces negligible signs of inflammatory pathophysiology and supports the development of significant level of protection against virulent Brucella challenge.


Assuntos
Adjuvantes Imunológicos/administração & dosagem , Antioxidantes/metabolismo , Vacina contra Brucelose/administração & dosagem , Brucelose/prevenção & controle , Estresse Oxidativo , Animais , Biomarcadores , Vacina contra Brucelose/imunologia , Brucella melitensis , Catalase/análise , Eritrócitos/metabolismo , Feminino , Peroxidação de Lipídeos , Lipídeos/administração & dosagem , Camundongos , Camundongos Endogâmicos BALB C , Superóxido Dismutase/análise , Vacinas de Produtos Inativados/administração & dosagem , Vacinas de Produtos Inativados/imunologia
13.
Indian J Surg Oncol ; 10(1): 65-71, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30948875

RESUMO

Postoperative pancreatic fistula (POPF) is the most feared complication after pancreaticoduodenectomy (PD) that leads to intra-abdominal abscess, sepsis, or bleeding and remains the single most important source of morbidity and mortality after PD. To minimize this dreaded complication, various surgical techniques and modifications of pancreaticoenteric reconstruction have been proposed. However, still POPF does occur even in experienced hands. We herein describe the outcome of 150 post PD patients who underwent duct-to-mucosa (DM) pancreaticojejunostomy (PJ) using a special technique, Blumgart's "through & through" U transpancreatic sutures. The technique is described in detail. Postoperative octreotide and metoclopramide were used in all patients for 3 days. An enhanced recovery (ERAS) protocol was followed in a subset of patients. All patients were ASA grade 1 and had adenocarcinoma of the periampullary region/pancreatic head and underwent standard pylorus resecting PD after due optimization. Eighty-eight (58.7%) patients had pancreatic duct < 3 mm and pancreatic texture was soft to very soft in 112 (74.6%) patients. There was only one International Study Group of Pancreatic Surgery (ISGPS) grade C POPF with concomitant hemorrhage. Five patients developed ISGPS grade B and two grade C, delayed gastric emptying (DGE). There was no 30-day mortality. The average length of hospital stay was 7.3 ± 4.2 days with a median of 6 days in the ERAS subset of patients. Blumgart's "through & through" DMPJ technique is very helpful in reducing the POPF and other complications even in high-risk pancreas (i.e., soft with a small pancreatic duct) and is easy to learn and perform.

14.
Benef Microbes ; 10(2): 149-154, 2019 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-30638396

RESUMO

Acute diarrhoea is one of the leading causes of mortality in infants and young children. Evidence suggests that probiotics can reduce diarrhoea duration. As the effects of probiotics are strain specific, the effect of Bacillus clausii UBBC-07, a safe probiotic strain in the treatment of acute diarrhoea in children was studied. The double blind, randomised, placebo-controlled, parallel group multicentric study was conducted at two outpatient facility sites in Lucknow, India. Children aged six months to five years suffering from acute diarrhoea, were randomly assigned to receive either probiotic (B. clausii UBBC-07) spore suspension or placebo suspension twice daily apart from oral rehydration solution (ORS). The duration of treatment was for five days with a follow -up until the 10th day. Outcomes evaluated were duration and frequency of diarrhoea, consistency of stool, fever and vomiting. The duration of diarrhoea was significantly shorter (P<0.05) in patients who received B. clausii suspension (75.66±13.23 h) than in placebo treated group (81.6±15.43 h). The average daily number of stools (frequency) was 8.67±3.42 at baseline in treatment group receiving B. clausii and 8.53±3.19 in placebo group. By day 4, there was a significant reduction (P<0.01) in frequency of stools in probiotic treated group (3.46±0.66) as compared to placebo group (4.57±1.59). Improvement in stool consistency was also observed in the probiotic treated group as compared to the placebo group. There was no effect on vomiting and duration of fever. B. clausii UBBC-07 significantly decreased the duration and frequency of diarrhoea as compared to placebo indicating effectiveness of strain in the treatment of acute diarrhoea in children and could be a safe alternative to antibiotics.


Assuntos
Bacillus clausii/crescimento & desenvolvimento , Diarreia/terapia , Probióticos/administração & dosagem , Fenômenos Químicos , Pré-Escolar , Diarreia/patologia , Método Duplo-Cego , Fezes/química , Feminino , Humanos , Índia , Lactente , Masculino , Placebos/administração & dosagem , Fatores de Tempo , Resultado do Tratamento
15.
Curr Genet ; 65(2): 561-573, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30467716

RESUMO

Spliceosome disassembly is catalyzed by the NineTeen-related (NTR) complex, which is constituted by several proteins, including Cwc23, Ntr1, and Ppr43. Cwc23 is an essential J-protein in Saccharomyces cerevisiae that recruits Ntr1, an NTC-related G-patch protein, to the spliceosome. Ntr1 interacts with Prp43, a DExD/H box RNA helicase protein, which facilitates the disassembly of spliceosomal intermediates. The interaction between Ntr1 and Prp43 is conserved and crucial for the disassembly process. However, the J-protein component of this complex is not studied in other eukaryotes. In silico analysis supported by results of yeast complementation and two-hybrid studies suggests that while Prp43 is highly conserved, both Ntr1 and Cwc23 are co-evolving components of the disassembly triad. The J-domain of Cwc23, which is otherwise dispensable for its function, is highly conserved, whereas the functionally critical C-terminus has significantly diverged in Cwc23 orthologs. Some eukaryotic orthologs of Cwc23 contain a distinct RNA recognition motif at their C-terminus and are able to bind RNA in vitro. Based on the results presented in this study, we propose that RNA-binding activity in some eukaryotic orthologs of Cwc23 might provide additional functional diversity or robustness to the J-protein/Hsp70 machine in spliceosomal remodelling processes.


Assuntos
Evolução Biológica , RNA/genética , RNA/metabolismo , Spliceossomos/metabolismo , Biologia Computacional/métodos , Bases de Dados Genéticas , Modelos Moleculares , Complexos Multiproteicos/metabolismo , Ligação Proteica , Conformação Proteica , RNA/química , Processamento de RNA , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/química , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Relação Estrutura-Atividade
17.
Indian J Endocrinol Metab ; 22(3): 362-367, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30090728

RESUMO

Background: Total thyroidectomy (TT) with a uniform technique of capsular dissection (CD) is the preferred technique worldwide. The aim of study is to analyze the impact of uniform technique of CD for done as primary surgery at an endocrine surgery training centre. Patients and Methods: Retrospective review from 1995 to 2009. Data collected from hospital records and follow-up. Results: One thousand and thirty-eight cases were included, with mean age 42.91 ± 13.48 years; male:female - 1:2.2; mean duration of goiter - 99.83 ± 105.1 months; 67.8% were euthyroid and 30.7% - hyperthyroid at initial presentation; 35.5% were malignant. Surgery includes TT alone - 77.7% and TT with lymph nodes dissection - 22.3%; sternotomy required in 1.2% and thoracotomy in 0.1%; tracheomalacia present in 3.9%; however, tracheostomy required in 4.5% and parathyroid autotransplantation in 21%; Peroperative mean gross gland weight was 124.34 ± 129.85 g. Complications include hypocalcemia (temporary - 35.9%; permanent - 1.3%); recurrent laryngeal nerve palsy (temporary - 2.7%; permanent - 91%); hemorrhage - 1.3%; and various others. Conclusion: TT with uniform technique of CD is a safe procedure. Certain risk factors may predispose to complications, which can be avoided and managed adequately if anticipated beforehand.

18.
Leuk Res ; 71: 82-88, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30025280

RESUMO

BACKGROUND: The Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) are associated with increases in janus kinase 2 (JAK2) signaling, often resulting from the JAK2 V617F mutation. LY2784544 (gandotinib) is a potent, selective, small-molecule inhibitor of JAK2 that has potential dose-dependent selectivity for the JAK2 V617F mutation and may inhibit additional JAK2 mutant isoforms in nonclinical testing. METHODS: A multicenter, single-arm, outpatient phase 2 study evaluated the efficacy, safety, and pharmacokinetics (PK) of gandotinib administered to patients (120 mg once daily) with MPNs, including polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF). Between May 2012 and March 2015, 138 patients received at least one dose of study drug. FINDINGS: Most frequent Grade 3 or 4 treatment-emergent adverse events that were considered study-drug related were anemia (11.6%), hyperuricemia (3.2%), fatigue (2.9%), diarrhea (2.2%), and thrombocytopenia (2.2%). Overall response rates (ORRs) in patients with JAK2 V617F-mutated PV, ET, and MF were 95%, 90.5%, and 9.1%, respectively, while patients with ET and MF without the JAK2 V617F mutations had ORRs of 43.7% and 0%, respectively. INTERPRETATIONS: LY2784544 demonstrated efficacy in JAK2 V617F-mutated MPNs, including in patients previously on ruxolitinib therapy, who had an ORR of 3.3%. At the 1-year visit, 44% of patients experienced a ≥50% improvement in the MPN-Symptom Assessment Form Total Symptom Score, and 26% of patients had a 50% reduction in Brief Fatigue Inventory score.


Assuntos
Antineoplásicos/uso terapêutico , Imidazóis/uso terapêutico , Policitemia Vera/tratamento farmacológico , Mielofibrose Primária/tratamento farmacológico , Pirazóis/uso terapêutico , Piridazinas/uso terapêutico , Trombocitemia Essencial/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Janus Quinase 2/genética , Masculino , Pessoa de Meia-Idade , Mutação , Transtornos Mieloproliferativos/tratamento farmacológico , Transtornos Mieloproliferativos/genética , Policitemia Vera/genética , Trombocitemia Essencial/genética
19.
3 Biotech ; 8(5): 227, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29719769

RESUMO

Barnyard (Echinochloa frumentacea) and finger (Eleusine coracana) millet growing at northwestern Himalaya were explored for the α-amylase inhibitor (α-AI). The mature seeds of barnyard millet variety PRJ1 had maximum α-AI activity which increases in different developmental stage. α-AI was purified up to 22.25-fold from barnyard millet variety PRJ1. Semi-quantitative PCR of different developmental stages of barnyard millet seeds showed increased levels of the transcript from 7 to 28 days. Sequence analysis revealed that it contained 315 bp nucleotide which encodes 104 amino acid sequence with molecular weight 10.72 kDa. The predicted 3D structure of α-AI was 86.73% similar to a bifunctional inhibitor of ragi. In silico analysis of 71 α-AI protein sequences were carried out for biochemical features, homology search, multiple sequence alignment, phylogenetic tree construction, motif, and superfamily distribution of protein sequences. Analysis of multiple sequence alignment revealed the existence of conserved regions NPLP[S/G]CRWYVV[S/Q][Q/R]TCG[V/I] throughout sequences. Superfam analysis revealed that α-AI protein sequences were distributed among seven different superfamilies.

20.
Malays Orthop J ; 12(1): 31-35, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29725510

RESUMO

Introduction: Osteoporosis (OP) is a major health problem in the older population. The aim of the study was to assess the role of serum osteoprotegerin (OPG) as a diagnostic indicator of primary osteoporosis in peri- and post-menopausal women in an Indian population. Materials and Methods: After ethical approval, 90 cases (45 cases and 45 controls) of peri- and post-menopausal females above 40 years of age presenting to our outpatient department were included in the study. It was a case controlled study conducted between July 2014 to July 2015. Based on the clinical features, t-score and radiological evidence from the DEXA scan, they were equally divided into two groups (cases and controls). Serum osteoprotegerin (OPG) levels were measured amongst cases and controls. Results: The total calcium (mg/dl) level was lower among the cases and the difference was significant (p-Value= <0.001). Similarly, alkaline phosphatase (u/l), osteoprotegerin (u/ml) levels were higher in the cases as compared to controls and the difference was significant (p-Value= <0.001). The mean osteoprotegerin level showed a slight increase with increase in severity of the grading of BMD of spine. The results suggested a cut-off value of ≥10.5 u/ml (86.7% sensitive and 80% specific with accuracy of 84.5%) between normal and osteoporosis. Conclusion: From the present study, we conclude that osteoprotegerin is a valid biomarker to diagnose postmenopausal women with low bone mineral density.

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