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1.
Nature ; 580(7804): E9, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32322057

RESUMO

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

2.
Nature ; 569(7756): 355-360, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31092942

RESUMO

Hybrid classical-quantum algorithms aim to variationally solve optimization problems using a feedback loop between a classical computer and a quantum co-processor, while benefiting from quantum resources. Here we present experiments that demonstrate self-verifying, hybrid, variational quantum simulation of lattice models in condensed matter and high-energy physics. In contrast to analogue quantum simulation, this approach forgoes the requirement of realizing the targeted Hamiltonian directly in the laboratory, thus enabling the study of a wide variety of previously intractable target models. We focus on the lattice Schwinger model, a gauge theory of one-dimensional quantum electrodynamics. Our quantum co-processor is a programmable, trapped-ion analogue quantum simulator with up to 20 qubits, capable of generating families of entangled trial states respecting the symmetries of the target Hamiltonian. We determine ground states, energy gaps and additionally, by measuring variances of the Schwinger Hamiltonian, we provide algorithmic errors for the energies, thus taking a step towards verifying quantum simulation.

4.
Nature ; 564(7736): 439-443, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30405246

RESUMO

Stimulator of interferon genes (STING) is a receptor in the endoplasmic reticulum that propagates innate immune sensing of cytosolic pathogen-derived and self DNA1. The development of compounds that modulate STING has recently been the focus of intense research for the treatment of cancer and infectious diseases and as vaccine adjuvants2. To our knowledge, current efforts are focused on the development of modified cyclic dinucleotides that mimic the endogenous STING ligand cGAMP; these have progressed into clinical trials in patients with solid accessible tumours amenable to intratumoral delivery3. Here we report the discovery of a small molecule STING agonist that is not a cyclic dinucleotide and is systemically efficacious for treating tumours in mice. We developed a linking strategy to synergize the effect of two symmetry-related amidobenzimidazole (ABZI)-based compounds to create linked ABZIs (diABZIs) with enhanced binding to STING and cellular function. Intravenous administration of a diABZI STING agonist to immunocompetent mice with established syngeneic colon tumours elicited strong anti-tumour activity, with complete and lasting regression of tumours. Our findings represent a milestone in the rapidly growing field of immune-modifying cancer therapies.


Assuntos
Benzimidazóis/química , Benzimidazóis/farmacologia , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/imunologia , Desenho de Fármacos , Proteínas de Membrana/agonistas , Animais , Benzimidazóis/administração & dosagem , Benzimidazóis/uso terapêutico , Humanos , Ligantes , Proteínas de Membrana/imunologia , Camundongos , Modelos Moleculares , Nucleotídeos Cíclicos/metabolismo
5.
Nature ; 552(7685): 374-377, 2017 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-29211720

RESUMO

Blazars are active galactic nuclei, which are powerful sources of radiation whose central engine is located in the core of the host galaxy. Blazar emission is dominated by non-thermal radiation from a jet that moves relativistically towards us, and therefore undergoes Doppler beaming. This beaming causes flux enhancement and contraction of the variability timescales, so that most blazars appear as luminous sources characterized by noticeable and fast changes in brightness at all frequencies. The mechanism that produces this unpredictable variability is under debate, but proposed mechanisms include injection, acceleration and cooling of particles, with possible intervention of shock waves or turbulence. Changes in the viewing angle of the observed emitting knots or jet regions have also been suggested as an explanation of flaring events and can also explain specific properties of blazar emission, such as intra-day variability, quasi-periodicity and the delay of radio flux variations relative to optical changes. Such a geometric interpretation, however, is not universally accepted because alternative explanations based on changes in physical conditions-such as the size and speed of the emitting zone, the magnetic field, the number of emitting particles and their energy distribution-can explain snapshots of the spectral behaviour of blazars in many cases. Here we report the results of optical-to-radio-wavelength monitoring of the blazar CTA 102 and show that the observed long-term trends of the flux and spectral variability are best explained by an inhomogeneous, curved jet that undergoes changes in orientation over time. We propose that magnetohydrodynamic instabilities or rotation of the twisted jet cause different jet regions to change their orientation and hence their relative Doppler factors. In particular, the extreme optical outburst of 2016-2017 (brightness increase of six magnitudes) occurred when the corresponding emitting region had a small viewing angle. The agreement between observations and theoretical predictions can be seen as further validation of the relativistic beaming theory.

6.
HIV Med ; 22(6): 423-433, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33529489

RESUMO

OBJECTIVES: Dolutegravir (DTG) is widely recommended within three-drug regimens. However, similar efficacy and tolerability have also been achieved with DTG within two-drug regimens in clinical trials. This study evaluated the real-world effectiveness and discontinuations in people living with HIV-1 (PLHIV) switching to DTG with lamivudine (3TC) or rilpivirine (RPV). METHODS: This was a one-arm meta-analysis utilizing data from a systematic literature review. Data from real-world evidence studies of DTG + RPV and DTG + 3TC were extracted, pooled and analysed. The primary outcome was the proportion of patients with viral failure (VF; ≥ 50 copies/mL in two consecutive measurements and/or ≥ 1000 copies/mL in a single measurement) at week 48 (W48) and week 96 (W96). Other outcomes included virological suppression (VS; < 50 copies/mL) and discontinuations (W48 and W96). Estimates were calculated for VF, VS as per snapshot (VSS) and on treatment analysis (VSOT), and discontinuations. RESULTS: Pooled mean estimates of VF for DTG + 3TC and DTG + RPV were 0.8% [95% confidence interval (CI): 0.4-1.3] and 0.6% (95% CI: 0.0-1.6), respectively, at W48. VSS rate at W48 was 85.0% (95% CI: 82.3-87.5) for DTG + 3TC regimen and 92.4% (95% CI: 85.0-97.7) in the DTG + RPV regimen. The DTG + 3TC and DTG + RPV regimens led to discontinuations in 13.6% (95% CI: 11.1-16.2) and 7.2% (95% CI: 2.1-14.4) of patients, respectively, at W48. Similar results were observed at W96. CONCLUSIONS: Treatment with DTG + 3TC or DTG + RPV in clinical practice provides a low rate of VF and a high rate of VS when initiated in virologically suppressed PLHIV with diverse backgrounds.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Fármacos Anti-HIV/efeitos adversos , Infecções por HIV/tratamento farmacológico , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Humanos , Oxazinas/uso terapêutico , Piperazinas , Piridonas/uso terapêutico
7.
J Vector Borne Dis ; 58(4): 306-310, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35381818

RESUMO

BACKGROUND & OBJECTIVES: Malaria control strategies for a particular area largely depends on the correct identification of the mosquito species prevalent in that area. This study aimed to develop an android mobile app named 'Pictorial Indian anophelines key', which can be used to identify the 58 species of Indian female adult anophelines based on morphological characteristics. METHODS: The pre-requisite to use this app requires a minimum basic knowledge of mosquito morphological characteristics and features. The user needs to view the collected mosquito under a dissecting binocular microscope and has to select the observations on the app presented in the form of labelled picture format. The app uses a divide and conquer algorithm which narrows the selection from genus level to final identification of species. RESULTS: The app is user-friendly, quick and it accurately identifies the mosquito species in a maximum of six consecutive clicks. The result displays a complete image of identified mosquito along with its quick identification features. It can be used for both subgenus Cellia and Anopheles. INTERPRETATION & CONCLUSION: This pictorial key-based mobile app could be helpful for entomologists, malariologists, researchers, public health workers as well as students in the quick and correct identification of anopheline mosquitoes prevalent in India which in turn could be helpful in devising appropriate approaches towards malaria control and prevention. The app can be modified as per future requirements.


Assuntos
Anopheles , Malária , Aplicativos Móveis , Animais , Feminino , Humanos , Índia , Malária/diagnóstico , Malária/prevenção & controle
8.
Med J Armed Forces India ; 77(4): 397-402, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34594066

RESUMO

BACKGROUND: Our hospital began work on formulating its own critical care air transport team (CCATT) and patient transfer unit (PTU) in 2007. A total of 293 patients have been evacuated by air using the various models of the PTU from April 2008 to February 2017. This study has been undertaken to formulate a protocol for activation of CCATT for aeromedical evacuation that best suits our setup keeping in view the availability of electromedical equipment, manpower and aircrafts. METHODS: The study is a cross-sectional study involving patients who were air evacuated between January 2010 to February 2017. Statistical analysis tests were performed to compare and analyze the two scoring systems to find out the sensitivity and specificity of the two scoring systems and to find out the degree of agreement. RESULTS: The data using each scoring system were compared with actual requirement of CCATT based on recommendation of team leader of each CCATT mission and available data of each patient. It was observed that the old scoring system showed poor agreement with kappa coefficient of 0.162. The new scoring system based on modified early warning physiological score showed good agreement with kappa coefficient of 0.895. CONCLUSION: CCATT can be activated by peripheral medical echelons based on objective criteria rather than subjective ones so that optimal use of resources can be carried out not only in peace time but also during mass casualty scenarios such as natural calamities or war.

9.
Anal Bioanal Chem ; 411(16): 3477-3495, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31093696

RESUMO

The detection of computer-generated document forgeries has always been a challenging task for forensic document examiners (FDE). With the aim to support the examination processes, Schottky field emission scanning electron microscopy with energy-dispersive X-ray spectroscopy (FE-SEM-EDS) is explored as a recent tool to analyze black toners obtained from laser printers and photocopier machines. Forty samples each from the laser printer and photocopier machines are procured and studied for morphological features, elemental profile, and multivariate analysis. The acquired SEM images and spectra are evaluated to discriminate and classify the toners having a different source of origin. Multivariate analysis is applied to develop a model of classification to successfully classify the printed documents on the basis of the similarities and differences in their composition. Hierarchical cluster analysis (HCA) discriminates the printouts in the forms of groups based on their chemical composition. The laser printer and the photocopier printed documents are grouped into 11 and eight clusters, respectively, based on their elemental composition. Cross-validation is further conducted to assess the capabilities of developed principal component analysis (PCA) and linear discriminant analysis (LDA) models for the examination of printouts from unknown origin. Graphical abstract.

10.
J Postgrad Med ; 65(4): 212-218, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31204726

RESUMO

Context: Globally, around half of all under-5 deaths are attributable to undernutrition. The magnitude of child undernutrition in India is one of the highest in the world. Responsive feeding that has the potential to optimize nutrition and development depends on a "healthy mother". Objectives: The objective of this study was to find out the magnitude and determinants of maternal depression among mothers of infants who attended immunization clinic in a rural medical college in central India and observe its association with infant-feeding practices and nutritional status of infants. Study Design: This was an analytical cross-sectional study. Materials and Methods: Study was conducted among consecutively chosen 300 mothers and their infants who visited the immunization clinic of hospital during May-September, 2016. Data were collected individually by interviewing each mother, and anthropometry of her infant was done. The mothers with depression were diagnosed according to the 10-item Edinburgh Postnatal Depression Scale. Magnitude of depression has been reported using frequency and percentage, whereas association has been studied using prevalence odds ratio with 95% confidence interval (CI) and logistic regression at 0.05 significance level. Results: The magnitude of maternal depression was 19% (95% CI 14.4-23.5). Mothers with depression had significantly higher odds for not indulging in responsive feeding. Maternal education had significant association with maternal depression after adjusting for other variables. Conclusions: Burden of maternal depression is high among mothers of infants who attended immunization clinic in a rural medical college in central India and is significantly associated with nonresponsive feeding practices.


Assuntos
Depressão/fisiopatologia , Comportamento Alimentar/psicologia , Transtornos da Nutrição do Lactente/psicologia , Mães/psicologia , Estado Nutricional , Adulto , Estudos Transversais , Depressão/epidemiologia , Feminino , Humanos , Índia/epidemiologia , Lactente , Transtornos da Nutrição do Lactente/epidemiologia , Fenômenos Fisiológicos da Nutrição do Lactente , Modelos Logísticos , Masculino , Razão de Chances , Prevalência , População Rural
11.
Acta Virol ; 62(2): 179-190, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29895159

RESUMO

Considering the need for discovery of new antiviral drugs, in view to combat the issue of resistance particularly to anti-influenza drugs, a series of 2'-amino, 3'-amino and 2', 4'-dihydroxy chalcone derivatives were designed. Structure-based drug design was used to design inhibitors of influenza virus - H1N1 neuraminidase enzyme. These were further optimized by a combination of iterative medicinal chemistry principles and molecular docking. Based on the best docking scores, some chalcone derivatives were synthesized and characterized by infrared spectroscopy (IR) and proton nuclear magnetic resonance (NMR). The molecules were evaluated for their anti-influenza action against influenza A/Pune isolate/2009 (H1N1) virus by in vitro enzyme-based assay (neuraminidase inhibition assay). We have then selected few of them for multinuclear NMR studies, 31P NMR, in order to probe the molecular mechanism of their antiviral action. Reasonably good correlation between docking scores; anti-influenza activity; and 31P NMR results were observed. The computational predictions were in consensus with the experimental results. It was observed that among tested compounds, derivative 1A, viz. 2', 4'-dihydroxy-4-methoxy chalcone, showed highest activity (IC50 = 2.23 µmol/l) against the virus under study. This derivative 1A can be explored further to provide a future therapeutic option for the treatment and prophylaxis of H1N1 viral infections.


Assuntos
Antivirais/química , Inibidores Enzimáticos/química , Vírus da Influenza A Subtipo H1N1/enzimologia , Antivirais/farmacologia , Membrana Celular , Desenho de Fármacos , Inibidores Enzimáticos/farmacologia , Humanos , Vírus da Influenza A Subtipo H1N1/química , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Influenza Humana/virologia , Espectroscopia de Ressonância Magnética , Simulação de Acoplamento Molecular , Neuraminidase/química , Relação Estrutura-Atividade
12.
Acta Virol ; 62(2): 208-213, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29895163

RESUMO

The etiological agent remained unidentified in a large number of patients hospitalized for acute encephalitis syndrome (AES) in 2008-2009 in Uttar Pradesh and Bihar, north India. All patients were found to present with fever and altered sensorium, while 28%, 19% and 13% showed hepatomegaly, splenomegaly and meningeal signs, respectively. Involvement mostly of children with abnormal hepatic features prompted us to undertake an exploratory study on viral hepatitis A to determine its association, if any, with hepatic derangements. AES patients (n = 2515) and healthy children (n = 167) were investigated for the presence of serum anti-hepatitis A virus (anti-HAV) IgM and anti-Japanese encephalitis (anti-JE) virus IgM by ELISA. Cerebrospinal fluids (CSFs, n = 595) and rectal swabs (n = 182) were examined for anti-HAV IgM and/or HAV RNA. Anti-HAV IgM was detected in the sera of 14.6% patients as against 6.6% of healthy children (p = 0.0042). Anti-JE virus IgM positivity was Keywords: acute encephalitis syndrome; cerebrospinal fluid; hepatitis A virus; anti-HAV IgM; non-Japanese encephalitis.


Assuntos
Encefalopatia Aguda Febril/virologia , Vírus da Hepatite A/fisiologia , Hepatite A/virologia , Encefalopatia Aguda Febril/sangue , Encefalopatia Aguda Febril/diagnóstico , Encefalopatia Aguda Febril/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antivirais/sangue , Criança , Pré-Escolar , Ensaio de Imunoadsorção Enzimática , Feminino , Hepatite A/sangue , Hepatite A/diagnóstico , Hepatite A/epidemiologia , Vírus da Hepatite A/genética , Humanos , Índia/epidemiologia , Lactente , Masculino , Pessoa de Meia-Idade , Adulto Jovem
13.
Kathmandu Univ Med J (KUMJ) ; 16(64): 338-344, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-31729350

RESUMO

Background Integrated curriculum enhances students' learning and the retention of knowledge. At Patan Academy of Health Sciences, integrated organ system based curriculum is used with Problem Based Learning as the principle teaching learning method to foster students' learning. In addition, other approaches of integration were under taken such as integrated assessment; logical arrangement teaching learning methods (lectures and practicals); joint effort of faculty in curriculum planning and delivery; conducive environment to foster hidden curriculum. This study describes the perception of faculty and students on integration characteristics of Basic Science curriculum. Objective To measure the integration characteristics of Basic Science Curriculum. Method Tool was developed to measure integration characteristics of Basic Science Curriculum and ensure whether such planned integration has been achieved. Mixed method was used to measure the perception of the integration characteristics i) quantitatively by questionnaire survey to faculty and students ii) qualitatively by in-depth interview of students. Result Both faculty and students perceived that all the blocks in Basic Science was well integrated in the quantitative questionnaire survey. But, in the in-depth interview, students perceived integration of curriculum in organ system blocks were better integrated compared to Principle of Human Biology blocks where fundamentals of basic science disciplines were delivered. Students reflected that Problem Based Learning not only integrated Basic Science disciplines but also with clinical sciences and the social context. But, students perceived that Community Health Sciences curriculum was not so well integrated with Basic Science subjects. Conclusion Overall, this study showed that planned integration in Basic Science curriculum was successfully executed during curriculum implementation.


Assuntos
Currículo , Educação de Graduação em Medicina/métodos , Aprendizagem , Aprendizagem Baseada em Problemas/métodos , Humanos , Inquéritos e Questionários
14.
Epidemiol Infect ; 145(2): 310-315, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27780494

RESUMO

Faecal specimens collected from outbreak (n = 253) and sporadic (n = 147) cases of acute gastroenteritis that occurred in western India between 2006 and 2014 were tested for group C rotavirus (GCR) using partial VP6 gene-based RT-PCR. All specimens were tested previously for the presence of other viral and bacterial aetiological agents by conventional methods. The rate of GCR detection was 8·6% and 0·7% in outbreak and sporadic cases, respectively. GCR infections prevailed in outbreaks reported from rural areas (10·9%) compared to urban areas (1·6%). Clinical severity score of the patients with GCR infection (n = 23) indicated severe disease in the majority (70%) of cases. The age distribution analysis indicated 52·1% of GCR infections in children aged <10 years. The male:female ratio in GCR-positive patients was 2·3:1. Of the 23 GCR-positive cases, 17 (73·9%) had a sole GCR infection and six had mixed infections with other viral and/or bacterial agents. Phylogenetic analysis of nucleotide sequences classified GCR strains of the study in to I2 genotype of the VP6 gene. This is the first study to show the occurrence of GCR in gastroenteritis outbreaks in India.


Assuntos
Surtos de Doenças , Gastroenterite/epidemiologia , Genótipo , Infecções por Rotavirus/epidemiologia , Rotavirus/classificação , Rotavirus/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos Virais/genética , Proteínas do Capsídeo/genética , Criança , Pré-Escolar , Coinfecção/epidemiologia , Coinfecção/patologia , Coinfecção/virologia , Fezes/virologia , Feminino , Gastroenterite/patologia , Gastroenterite/virologia , Técnicas de Genotipagem , Humanos , Índia/epidemiologia , Lactente , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Rotavirus/isolamento & purificação , Infecções por Rotavirus/patologia , Infecções por Rotavirus/virologia , Índice de Gravidade de Doença , Distribuição por Sexo , Adulto Jovem
15.
Spinal Cord ; 55(2): 126-130, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27527240

RESUMO

STUDY DESIGN: Randomized longitudinal comparative study. OBJECTIVES: To compare the efficacy of lamotrigine and amitriptyline in the management of traumatic spinal cord injury (SCI)-induced neuropathic pain (NP). SETTING: Sawai Man Singh Medical College and Hospital, Jaipur, India. METHODS: A total of 147 individuals with NP were randomized for a 3-week trial of either amitriptyline or lamotrigine. Amitriptyline was administered orally at doses of 25, 50 and 100 mg once daily at night time, and lamotrigine was administered orally at doses of 25, 50 and 100 mg twice daily, both for 1 week by means of optional titration. Assessment of NP was done at baseline and thereafter at 1, 2 and 3 weeks using Short-form MC Gill Pain Questionnaire-2 (SFMPQ2) scores. RESULTS: There was a significant difference between the mean values of the SFMPQ2 score at baseline and those at each follow-up for amitriptyline. Similar results were seen in the lamotrigine group. When the differences in mean SFMPQ2 scores at different time frames from baseline were compared with those of the other group, values were found to be nonsignificant as seen on the Mann-Whitney U-test. CONCLUSIONS: These findings support the use of both amitriptyline and lamotrigine in the management of NP after traumatic SCI.


Assuntos
Amitriptilina/administração & dosagem , Neuralgia/tratamento farmacológico , Neuralgia/epidemiologia , Traumatismos da Medula Espinal/tratamento farmacológico , Traumatismos da Medula Espinal/epidemiologia , Triazinas/administração & dosagem , Administração Oral , Adolescente , Adulto , Anticonvulsivantes/administração & dosagem , Antidepressivos Tricíclicos/administração & dosagem , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Índia/epidemiologia , Lamotrigina , Estudos Longitudinais , Masculino , Neuralgia/diagnóstico , Medição da Dor/efeitos dos fármacos , Medição da Dor/métodos , Traumatismos da Medula Espinal/diagnóstico , Resultado do Tratamento , Adulto Jovem
16.
J Postgrad Med ; 63(2): 100-105, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28272063

RESUMO

BACKGROUND: Despite an increasing emphasis on workplace-based assessment (WPBA) during medical training, the existing assessment system largely relies on summative assessment while formative assessment is less valued. Various tools have been described for WPBA, mini-clinical evaluation exercise (mini-CEX) being one of them. Mini-CEX is well accepted in Western countries, however, reports of its use in India are scarce. We conducted this study to assess acceptability and feasibility of mini-CEX as a formative assessment tool for WPBA of surgical postgraduate students in an Indian setting. METHODS: Faculty members and 2nd year surgical residents were sensitized toward mini-CEX and requisite numbers of exercises were conducted. The difficulties during conduction of these exercises were identified, recorded, and appropriate measures were taken to address them. At the conclusion, the opinion of residents and faculty members regarding their experience with mini-CEX was taken using a questionnaire. The results were analyzed using simple statistical tools. RESULTS: Nine faculty members out of 11 approached participated in the study (81.8%). All 16 2nd year postgraduate surgical residents participated (100%). Sixty mini-CEX were conducted over 7 months. Each resident underwent 3-5 encounters. The mean time taken by the assessor for observation was 12.3 min (8-30 min) while the mean feedback time was 4.2 min (3-10 min). The faculty reported good overall satisfaction with mini-CEX and found it acceptable as a formative assessment tool. Three faculty members (33.3%) reported mini-CEX as more time-consuming while 2 (22.2%) found it difficult to carry the exercises often. All residents accepted mini-CEX and most of them reported good to high satisfaction with the exercises conducted. CONCLUSIONS: Mini-CEX is well accepted by residents and faculty as a formative assessment tool. It is feasible to utilize mini-CEX for WPBA of postgraduate students of surgery.


Assuntos
Competência Clínica/normas , Educação de Pós-Graduação em Medicina/normas , Avaliação Educacional/métodos , Feedback Formativo , Cirurgia Geral/educação , Internato e Residência/organização & administração , Local de Trabalho , Adulto , Avaliação Educacional/normas , Estudos de Viabilidade , Feminino , Grupos Focais , Humanos , Masculino , Pessoa de Meia-Idade , Observação
17.
J Radiol Prot ; 37(2): 379-389, 2017 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-28418936

RESUMO

Experiments have been carried out using the deposition-based Direct Thoron Progeny Sensors (DTPS) in a thoron experimental house. The objective was to study the thoron decay product characteristics such as the deposition velocities, spatial variability and dependence on aerosol particle concentrations. Since the deposition velocity is an important characteristic in the calibration of the DTPS, it is very important to study its dependence on aerosol concentration in a controlled environment. At low aerosol concentration (1500 particles/cm3) the mean effective deposition velocity was measured to be 0.159 ± 0.045 m h-1; at high aerosol concentration (30 000 particles/cm3) it decreased to 0.079 ± 0.009 m h-1. The deposition velocity for the attached fraction of the thoron decay products did not change with increasing aerosol concentration, showing measurement results of 0.048 ± 0.005 m h-1 and 0.043 ± 0.014 m h-1, respectively. At low particle concentration, the effective deposition velocity showed large scattering within the room at different distances from center. The attached fraction deposition velocity remained uniform at different distances from the wall. The measurements in the thoron experimental house can be used as a sensitivity test of the DTPS in an indoor environment with changing aerosol concentration. The uniform spatial distribution of thoron decay products was confirmed within the experimental house. This indicates that direct measurement of thoron decay product concentration should be carried out instead of inferring it from thoron gas concentration, which is very inhomogeneous within the experimental house.


Assuntos
Poluentes Radioativos do Ar/análise , Poluição do Ar em Ambientes Fechados/análise , Habitação , Monitoramento de Radiação/métodos , Produtos de Decaimento de Radônio/análise , Radônio/análise , Aerossóis , Movimentos do Ar , Calibragem , Exposição Ambiental , Modelos Teóricos
18.
Clin Endocrinol (Oxf) ; 85(3): 331-9, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-26998595

RESUMO

Immune checkpoint inhibitors are a new and effective class of cancer therapy, with ipilimumab being the most established drug in this category. The drugs' mechanism of action includes promoting the effector T cell response to tumours and therefore increased autoimmunity is a predictable side effect. The endocrine effects of these drugs include hypophysitis and thyroid dysfunction, with rare reports of adrenalitis. The overall incidence of hypophysitis with these medications is up to 9%. Primary thyroid dysfunction occurs in up to 15% of patients, with adrenalitis reported in approximately 1%. The mean onset of endocrine side effects is 9 weeks after initiation (range 5-36 weeks). Investigation and/or screening for hypophysitis requires biochemical and radiological assessment. Hypopituitarism is treated with replacement doses of deficient hormones. Since the endocrine effects of immune checkpoint inhibitors are classed as toxic adverse events, most authors recommend both discontinuation of the immune checkpoint inhibiting medication and 'high-dose' glucocorticoid treatment. However, this has been challenged by some authors, particularly if the endocrine effects can be managed (e.g. pituitary hormone deficiency), and the therapy is proving effective as an anticancer agent. This review describes the mechanism of action of immune checkpoint inhibitors and details the key clinical endocrine-related consequences of this novel class of immunotherapies.


Assuntos
Antineoplásicos/efeitos adversos , Doenças do Sistema Endócrino/induzido quimicamente , Hipofisite/induzido quimicamente , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/uso terapêutico , Pontos de Checagem do Ciclo Celular/imunologia , Humanos , Imunoterapia/efeitos adversos , Ipilimumab
19.
Hum Reprod ; 31(4): 854-65, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26851602

RESUMO

STUDY QUESTION: Does investigation of metabolic perturbations in endometrial tissue of women with dormant genital tuberculosis (GTB) during the window of implantation (WOI) assist in improving the understanding of endometrial receptivity? SUMMARY ANSWER: In dormant GTB cases significant alterations in endometrial tissue metabolites occur, largely related to energy metabolism and amino acid biosynthesis in dormant GTB cases. WHAT IS KNOWN ALREADY: As an intracellular pathogen, Mycobacterium tuberculosis strongly influences the metabolism of host cells causing metabolic dysregulation. It is also accepted that dormant GTB impairs the receptive status of the endometrium. Global metabolic profiling is useful for an understanding of disease progression and distinguishing between diseased and non-diseased groups. STUDY DESIGN, SIZE, DURATION: Endometrial tissue samples were collected from patients reporting at the tertiary infertility care center during the period September 2011-March 2013. Women having tested positive for GTB were considered as the study group (n = 24). Normal healthy women undergoing sterilization (n = 26) and unexplained infertile women with repeated IVF failure (n = 21) volunteered to participate as controls. PARTICIPANTS/MATERIALS, SETTING, METHODS: Endometrial tissue samples were collected 6-10 days after confirmation of ovulation. PCR and BACTEC-460 culture were used for diagnosing GTB. Proton nuclear magnetic resonance (1H NMR) spectra of tissue were recorded using a 700 MHz Bruker Avance AV III spectrometer. Following phase and baseline correction of all NMR spectra by Bruker Topspin 2.1 software, spectral peak alignment of the data was performed. Multivariate analysis was applied to all spectra and individual metabolites identified and multiple correlation analysis was performed. MAIN RESULTS AND THE ROLE OF CHANCE: Leucine, isoleucine, acetate, lactate, glutamate, glutamine, methionine, lysine, creatine, glycogen, glycine, proline and choline were found to be significantly increased (P < 0.05) in endometrial tissue of women with dormant GTB compared with unexplained infertile women with repeated implantation failure. Valine, citrate, succinate and aspartate were also observed to be significantly up-regulated (P < 0.01). Furthermore, a significant decrease in glucose (P < 0.05), threonine (P < 0.05), tyrosine (P < 0.01) and phenylalanine (P < 0.0001) was observed in women with dormant GTB. Pearson's correlation analysis between the expression of various endometrial receptivity markers and metabolites showed a significant negative correlation (-0.236 to -0.545, P < 0.05). Also, the metabolites were positively correlated with endometrial receptivity markers (0.207 to 0.618, P < 0.05). LIMITATIONS, REASONS FOR CAUTION: It is often difficult to diagnose dormant GTB because it tends to exist without any clinical signs or symptoms. In addition, the diagnosis of GTB by culture remains a challenge due to low detection rates and its paucibacillary nature. Testing for prostate-specific antigen or the Y chromosome in order to account for the possible influences of recent exposure to semen on endometrial metabolism would be important. WIDER IMPLICATIONS OF THE FINDINGS: The metabolic changes associated with the dormant tubercle infection are of potential relevance to clinicians for the treatment of dormant GTB-related infertility. STUDY FUNDING/COMPETING INTERESTS: Government of India, Indian Council of Medical Research. There are no conflicts of interest.


Assuntos
Infecções Assintomáticas , Endométrio/metabolismo , Interações Hospedeiro-Patógeno , Metabolômica/métodos , Mycobacterium tuberculosis/fisiologia , Tuberculose dos Genitais Femininos/metabolismo , Adulto , Aminoácidos/biossíntese , Biomarcadores/metabolismo , Biópsia , Endométrio/microbiologia , Endométrio/patologia , Metabolismo Energético , Feminino , Humanos , Índia , Infertilidade Feminina/etiologia , Mycobacterium tuberculosis/isolamento & purificação , Ressonância Magnética Nuclear Biomolecular , Centros de Atenção Terciária , Tuberculose dos Genitais Femininos/microbiologia , Tuberculose dos Genitais Femininos/patologia , Tuberculose dos Genitais Femininos/fisiopatologia
20.
Epidemiol Infect ; 144(13): 2709-18, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-26489400

RESUMO

During June-August 2013, 25 US states reported 631 cyclosporiasis cases including Nebraska and Iowa where a regional investigation implicated common-source imported salad mix served in two chain restaurants. At least two common-origin growing fields were likely sources of contaminated romaine lettuce. Using producer- and distributor-provided data, we conducted a grower-specific traceforward investigation to reveal exposures of ill US residents elsewhere who reported symptom onset during 11 June-1 July 2013, the time period established in the Nebraska and Iowa investigation. Romaine lettuce shipped on 2-6 June from one of these Mexico-origin growing fields likely caused cyclosporiasis in 78 persons reporting illness onsets from 11 June to 1 July in Nebraska, Texas, and Florida. Nationwide, 97% (314/324) of persons confirmed with cyclosporiasis with symptom onset from 11 June to 1 July 2013 resided in 11 central and eastern US states receiving approximately two-thirds of romaine lettuce from this field. This grower's production practices should be investigated to determine potential sources of contamination and to develop recommendations to prevent future illnesses.


Assuntos
Cyclospora/isolamento & purificação , Ciclosporíase/epidemiologia , Surtos de Doenças , Parasitologia de Alimentos , Lactuca/parasitologia , Comércio , Ciclosporíase/parasitologia , Florida/epidemiologia , Humanos , México , Nebraska/epidemiologia , Restaurantes , Texas/epidemiologia
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