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1.
BMC Pregnancy Childbirth ; 19(1): 41, 2019 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-30674286

RESUMO

BACKGROUND: Inadequately treated, preeclampsia and eclampsia (PE/E) may rapidly lead to severe complications in both mothers and neonates, and are estimated to cause 60,000 global maternal deaths annually. Simulation-based training on obstetric and neonatal emergency management has demonstrated promising results in low- and middle-income countries. However, the impact of simulation training on use of evidence-based practices for PE/E diagnosis and management in low-resource settings remains unknown. METHODS: This study was based on a statewide, high fidelity in-situ simulation training program developed by PRONTO International and implemented in collaboration with CARE India on PE/E management in Bihar, India. Using a mixed methods approach, we evaluated changes over time in nurse mentees' use of evidence-based practices during simulated births at primary health clinics. We compared the proportion and efficiency of evidence-based practices completed during nurse mentees' first and last participation in simulated PE/E cases. Twelve semi-structured interviews with nurse mentors explored barriers and enablers to high quality PE/E care in Bihar. RESULTS: A total of 39 matched first and last simulation videos, paired by facility, were analyzed. Videos occurred a median of 62 days apart and included 94 nurses from 33 primary health centers. Results showed significant increases in the median number of 'key history questions asked,' (1.0 to 2.0, p = 0.03) and 'key management steps completed,' (2.0 to 3.0, p = 0.03). The time from BP measured to magnesium sulfate given trended downwards by 3.2 min, though not significantly (p = 0.06). Key barriers to high quality PE/E care included knowledge gaps, resource shortages, staff hierarchy between physicians and nurses, and poor relationships with patients. Enablers included case-based and simulation learning, promotion of teamwork and communication, and effective leadership. CONCLUSION: Simulation training improved the use of evidence-based practices in PE/E simulated cases and has the potential to increase nurse competency in diagnosing and managing complex maternal complications such as PE/E. However, knowledge gaps, resource limitations, and interpersonal barriers must be addressed in order to improve care. Teamwork, communication, and leadership are key mechanisms to facilitate high quality PE/E care in Bihar.


Assuntos
Eclampsia/enfermagem , Tutoria/métodos , Tocologia/educação , Papel do Profissional de Enfermagem , Pré-Eclâmpsia/enfermagem , Treinamento por Simulação/métodos , Adulto , Competência Clínica , Feminino , Humanos , Índia , Assistência Perinatal/métodos , Gravidez , Adulto Jovem
2.
J Proteome Res ; 17(8): 2611-2622, 2018 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-29939029

RESUMO

Earthworms ( Eisenia fetida) are vital members of the soil environment. Because of their sensitivity to many contaminants, monitoring earthworm metabolism may be a useful indicator of environmental stressors. Here, metabolic profiles of exposure to five chloroacetanilide herbicides and one enantiomer (acetochlor, alachlor, butachlor, racemic metolachlor, S-metolachlor, and propachlor) are observed in earthworm coelomic fluid using proton nuclear magnetic resonance spectroscopy (NMR) and gas chromatography-mass spectrometry (GC-MS). Multiblocked-orthogonal partial least-squares-discriminant analysis (MB-OPLS-DA) and univariate analysis were used to identify metabolic perturbations in carnitine biosynthesis, carbohydrate metabolism, lipid metabolism, nitrogen metabolism, and the tricarboxylic acid cycle. Intriguingly, stereospecific metabolic responses were observed between racemic metolachlor and S-metolachlor exposed worms. These findings support the utility of coelomic fluid in monitoring metabolic perturbations induced by chloroacetanilide herbicides in nontarget organisms and reveal specificity in the metabolic impacts of herbicide analogues in earthworms.


Assuntos
Acetamidas/metabolismo , Líquidos Corporais/química , Herbicidas/metabolismo , Oligoquetos/química , Animais , Líquidos Corporais/metabolismo , Carnitina/biossíntese , Metabolismo Energético , Monitoramento Ambiental/métodos , Cromatografia Gasosa-Espectrometria de Massas , Oligoquetos/metabolismo , Espectroscopia de Prótons por Ressonância Magnética
3.
BMC Pregnancy Childbirth ; 18(1): 420, 2018 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-30359240

RESUMO

BACKGROUND: Globally, an estimated 275,000 maternal deaths, 2.7 million neonatal deaths, and 2.6 million third trimester stillbirths occurred in 2015. Major improvements could be achieved by providing effective care in low- and middle-income countries, where the majority of these deaths occur. Mentoring programs have become a popular modality to improve knowledge and skills among providers in low-resource settings. Thus, a detailed understanding of interrelated factors affecting care provision and mentorship is necessary both to improve the quality of care and to maximize the impact of mentoring programs. METHODS: In partnership with the Government of Bihar, CARE India and PRONTO International implemented simulation-enhanced mentoring in 320 primary health clinics (PHC) across the state of Bihar, India from 2015 to 2017, within the context of the AMANAT mobile nurse mentoring program. Between June and August 2016, we conducted semi-structured interviews with 20 AMANAT nurse mentors to explore barriers and facilitators to optimal care provision and to implementation of simulation-enhanced mentorship in PHCs in Bihar. Data were analyzed using the thematic content approach. RESULTS: Mentors identified numerous factors affecting care provision and mentorship, many of which were interdependent. Such barriers included human resource shortages, nurse-nurse hierarchy, distance between labor and training rooms, cultural norms, and low skill level and resistance to change among mentees. In contrast, physical resource shortages, doctor-nurse hierarchy, corruption, and violence against providers posed barriers to care provision alone. Facilitators included improved skills and confidence among providers, inclusion of doctors in training, increased training frequency, establishment of strong mentor-mentee relationships, administrative support, and nursing supervision and feedback. CONCLUSIONS: This study has identified many interrelated factors affecting care provision and mentorship in Bihar. The mentoring program was not designed to address several barriers, including resource shortages, facility infrastructure, corruption, and cultural norms. These require government support, community awareness, and other systemic changes. Programs may be adapted to address some barriers beyond knowledge and skill deficiencies, notably hierarchy, violence against providers, and certain cultural taboos. An in-depth understanding of barriers and facilitators is essential to enable the design of targeted interventions to improve maternal and neonatal survival in Bihar and related contexts.


Assuntos
Serviços Médicos de Emergência/estatística & dados numéricos , Mentores/estatística & dados numéricos , Assistência Perinatal/estatística & dados numéricos , Atenção Primária à Saúde/estatística & dados numéricos , Treinamento por Simulação/métodos , Adulto , Atitude do Pessoal de Saúde , Atenção à Saúde/estatística & dados numéricos , Emergências , Feminino , Humanos , Índia , Recém-Nascido , Enfermeiras e Enfermeiros/estatística & dados numéricos , Gravidez , Avaliação de Programas e Projetos de Saúde , Pesquisa Qualitativa
4.
BMC Pregnancy Childbirth ; 18(1): 385, 2018 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-30268110

RESUMO

BACKGROUND: In India, the neonatal mortality rate is nearly double the Sustainable Development Goal target with more than half of neonatal deaths occurring in only four states, one of which is Bihar. Evaluations of immediate neonatal care and neonatal resuscitation skills in Bihar have demonstrated a need for significant improvement. However, barriers to evidence based practices in clinical care remain incompletely characterized. METHODS: To better understand such barriers, semi-structured interviews were conducted with 18 nurses who participated as mentors in the AMANAT maternal and child health quality improvement project, implemented by CARE India and the Government of Bihar. Nurse-mentors worked in primary health centers throughout Bihar facilitating PRONTO International emergency obstetric and neonatal simulations for nurse-mentees in addition to providing direct supervision of clinical care. Interviews focused on mentors' perceptions of barriers to evidence based practices in immediate neonatal care and neonatal resuscitation faced by mentees employed at Bihar's rural primary health centers. Data was analyzed using the thematic content approach. RESULTS: Mentors identified numerous interacting logistical, cultural, and structural barriers to care. Logistical barriers included poor facility layout, supply issues, human resource shortages, and problems with the local referral system. Cultural barriers included norms such as male infant preference, traditional clinical practices, hierarchy in the labor room, and interpersonal relations amongst staff as well as with patients' relatives. Poverty was described as an overarching structural barrier. CONCLUSION: Interacting logistical, cultural and structural barriers affect all aspects of immediate neonatal care and resuscitation in Bihar. These barriers must be addressed in any intervention focused on improving providers' clinical skills. Strategic local partnerships are vital to addressing such barriers and to contextualizing skills-based trainings developed in Western contexts to achieve the desired impact of reducing neonatal mortality.


Assuntos
Reanimação Cardiopulmonar/enfermagem , Bem-Estar do Lactente/estatística & dados numéricos , Serviços de Saúde Materna/normas , Mentores/estatística & dados numéricos , Assistência Perinatal/métodos , Barreiras de Comunicação , Feminino , Promoção da Saúde , Humanos , Índia , Lactente , Recém-Nascido , Masculino , Gravidez
5.
BMC Pediatr ; 18(1): 291, 2018 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-30176831

RESUMO

BACKGROUND: Globally, neonatal mortality accounts for nearly half of under-five mortality, and intrapartum related events are a leading cause. Despite the rise in neonatal resuscitation (NR) training programs in low- and middle-income countries, their impact on the quality of NR skills amongst providers with limited formal medical education, particularly those working in rural primary health centers (PHCs), remains incompletely understood. METHODS: This study evaluates the impact of PRONTO International simulation training on the quality of NR skills in simulated resuscitations and live deliveries in rural PHCs throughout Bihar, India. Further, it explores barriers to performance of key NR skills. PRONTO training was conducted within CARE India's AMANAT intervention, a maternal and child health quality improvement project. Performance in simulations was evaluated using video-recorded assessment simulations at weeks 4 and 8 of training. Performance in live deliveries was evaluated in real time using a mobile-phone application. Barriers were explored through semi-structured interviews with simulation facilitators. RESULTS: In total, 1342 nurses participated in PRONTO training and 226 NR assessment simulations were matched by PHC and evaluated. From week 4 to 8 of training, proper neck extension, positive pressure ventilation (PPV) with chest rise, and assessment of heart rate increased by 14%, 19%, and 12% respectively (all p ≤ 0.01). No difference was noted in stimulation, suction, proper PPV rate, or time to completion of key steps. In 252 live deliveries, identification of non-vigorous neonates, use of suction, and use of PPV increased by 21%, 25%, and 23% respectively (all p < 0.01) between weeks 1-3 and 4-8. Eighteen interviews revealed individual, logistical, and cultural barriers to key NR skills. CONCLUSION: PRONTO simulation training had a positive impact on the quality of key skills in simulated and live resuscitations throughout Bihar. Nevertheless, there is need for ongoing improvement that will likely require both further clinical training and addressing barriers that go beyond the scope of such training. In settings where clinical outcome data is unreliable, data triangulation, the process of synthesizing multiple data sources to generate a better-informed evaluation, offers a powerful tool for guiding this process.


Assuntos
Reanimação Cardiopulmonar/educação , Enfermeiros Obstétricos/educação , Síndrome do Desconforto Respiratório do Recém-Nascido/terapia , Serviços de Saúde Rural , Treinamento por Simulação , Competência Clínica , Parto Obstétrico , Frequência Cardíaca , Humanos , Índia , Recém-Nascido , Tutoria , Atenção Primária à Saúde , Avaliação de Programas e Projetos de Saúde , Melhoria de Qualidade , Taxa Respiratória
6.
Acta Paediatr ; 2018 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-29603791

RESUMO

AIM: Kangaroo mother care (KMC) is a safe and effective method of reducing neonatal mortality in resource-limited settings, but there has been a lack of data on the duration of skin-to-skin contact (SSC) in busy, low-resource newborn units. Previous studies of intermittent KMC suggest the duration of SSC ranged from 10 minutes to 17 hours per day. METHODS: This was an observational study of newborn infants born weighing less than 2000 g, which collected quantitative data on SSC over the first week after birth. The study took place in July 2016 in the newborn unit of a low-resource facility in Uganda. RESULTS: The mean daily duration of SSC over the first week after birth was three hours. This differed significantly from the World Health Organization recommendation of at least 20 hours of SSC per day. SSC was provided by mothers most of the time (73.5%), but other family members also took part, especially on the day of birth. CONCLUSION: Our study found a disappointingly low daily duration of SSC in this Ugandan newborn unit. However, advocacy and community education of SSC may help to decrease the stigma of KMC, improve overall acceptance and reduce the age at SSC initiation.

7.
J Paediatr Child Health ; 54(3): 260-266, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29080284

RESUMO

AIM: There are 2.7 million neonatal deaths annually, 75% of which occur in sub-Saharan Africa and South Asia. Effective treatment of hypoxaemia through tailored oxygen therapy could reduce neonatal mortality and prevent oxygen toxicity. METHODS: We undertook a two-part prospective study of neonates admitted to a neonatal unit in Nairobi, Kenya, between January and December 2015. We determined the prevalence of hypoxaemia and explored associations of clinical risk factors and signs of respiratory distress with hypoxaemia and mortality. After staff training on oxygen saturation (SpO2 ) target ranges, we enrolled a consecutive sample of neonates admitted for oxygen and measured SpO2 at 0, 6, 12, 18 and 24 h post-admission. We estimated the proportion of neonates outside the target range (≥34 weeks: ≥92%; <34 weeks: 89-93%) with 95% confidence intervals (CIs). RESULTS: A total of 477 neonates were enrolled. Prevalence of hypoxaemia was 29.2%. Retractions (odds ratio (OR) 2.83, 95% CI 1.47-5.47), nasal flaring (OR 2.68, 95% CI 1.51-4.75), and grunting (OR 2.47, 95% CI 1.27-4.80) were significantly associated with hypoxaemia. Nasal flaring (OR 2.85, 95% CI 1.25-6.54), and hypoxaemia (OR 3.06, 95% CI 1.54-6.07) were significantly associated with mortality; 64% of neonates receiving oxygen were out of range at ≥2 time points and 43% at ≥3 time points. CONCLUSION: There is a high prevalence of hypoxaemia at admission and a strong association between hypoxaemia and mortality in this Kenyan neonatal unit. Many neonates had out of range SpO2 values while receiving oxygen. Further research is needed to test strategies aimed at improving the accuracy of oxygen provision in low-resource settings.


Assuntos
Hipóxia/terapia , Doenças do Recém-Nascido/terapia , Oximetria , Oxigenoterapia , Feminino , Recursos em Saúde , Maternidades , Humanos , Hipóxia/epidemiologia , Hipóxia/mortalidade , Recém-Nascido , Doenças do Recém-Nascido/mortalidade , Quênia , Masculino , Razão de Chances , Oxigênio/sangue , Prevalência , Estudos Prospectivos
9.
BMC Pregnancy Childbirth ; 17(1): 252, 2017 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-28754111

RESUMO

BACKGROUND: As the global under-five mortality rate declines, an increasing percentage is attributable to early neonatal mortality. A quarter of early neonatal deaths are due to perinatal asphyxia. However, neonatal resuscitation (NR) simulation training in low-resource settings, where the majority of neonatal deaths occur, has achieved variable success. In Bihar, India, the poorest region in South Asia, there is tremendous need for a new approach to reducing neonatal morality. METHODS: This analysis aims to assess the impact of a novel in-situ simulation training program, developed by PRONTO International and implemented in collaboration with CARE India, on NR skills of nurses in Bihar. Skills were evaluated by clinical complexity of the simulated scenario, which ranged from level 1, requiring NR without a maternal complication, to level 3, requiring simultaneous management of neonatal and maternal complications. A total of 658 nurses at 80 facilities received training 1 week per month for 8 months. Simulations were video-recorded and coded for pre-defined clinical skills using Studiocode™. RESULTS: A total of 298 NR simulations were analyzed. As simulation complexity increased, the percentage of simulations in which nurses completed key steps of NR did not change, even with only 1-2 providers in the simulation. This suggests that with PRONTO training, nurses were able to maintain key skills despite higher clinical demands. As simulation complexity increased from level 1 to 3, time to completion of key NR steps decreased non-significantly. Median time to infant drying decreased by 7.5 s (p = 0.12), time to placing the infant on the warmer decreased by 21.7 s (p = 0.27), and time to the initiation of positive pressure ventilation decreased by 20.8 s (p = 0.12). Nevertheless, there remains a need for improvement in absolute time elapsed between delivery and completion of key NR tasks. CONCLUSIONS: PRONTO simulation training enabled nurses in Bihar to maintain core NR skills in simulation despite demands for higher-level triage and management. Although further evaluation of the PRONTO methodology is necessary to understand the full scope of its impact, this analysis highlights the importance of conducting and evaluating simulation training in low-resource settings based on simultaneous care of the mother-infant dyad.


Assuntos
Mortalidade Infantil/tendências , Bem-Estar do Lactente/estatística & dados numéricos , Tocologia/educação , Assistência Perinatal/métodos , Treinamento por Simulação/métodos , Adulto , Competência Clínica , Feminino , Humanos , Índia , Lactente , Pobreza , Gravidez , Serviços de Saúde Rural , Adulto Jovem
11.
Soft Matter ; 10(48): 9651-6, 2014 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-25366572

RESUMO

An anionic self-folding deep cavitand is capable of immobilizing unmodified proteins and enzymes at a supported lipid bilayer interface, providing a simple, soft bioreactive surface that allows enzymatic function under mild conditions. The adhesion is based on complementary charge interactions, and the hosts are capable of binding enzymes such as trypsin at the bilayer interface: the catalytic activity is retained upon adhesion, allowing selective reactions to be performed at the membrane surface.


Assuntos
Éteres Cíclicos/química , Bicamadas Lipídicas/química , Proteínas/química , Resorcinóis/química , Sequência de Aminoácidos , Ânions/química , Dados de Sequência Molecular , Ligação Proteica , Proteínas/metabolismo , Eletricidade Estática
12.
Antibiotics (Basel) ; 13(1)2024 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-38247636

RESUMO

Salmonella is a major foodborne pathogen and a leading cause of gastroenteritis in humans and animals. Salmonella is highly pathogenic and encompasses more than 2600 characterized serovars. The transmission of Salmonella to humans occurs through the farm-to-fork continuum and is commonly linked to the consumption of animal-derived food products. Among these sources, poultry and poultry products are primary contributors, followed by beef, pork, fish, and non-animal-derived food such as fruits and vegetables. While antibiotics constitute the primary treatment for salmonellosis, the emergence of antibiotic resistance and the rise of multidrug-resistant (MDR) Salmonella strains have highlighted the urgency of developing antibiotic alternatives. Effective infection management necessitates a comprehensive understanding of the pathogen's epidemiology and transmission dynamics. Therefore, this comprehensive review focuses on the epidemiology, sources of infection, risk factors, transmission dynamics, and the host range of Salmonella serotypes. This review also investigates the disease characteristics observed in both humans and animals, antibiotic resistance, pathogenesis, and potential strategies for treatment and control of salmonellosis, emphasizing the most recent antibiotic-alternative approaches for infection control.

13.
Subst Use Misuse ; 48(5): 415-9, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23461625

RESUMO

Google Inc.'s digitized book library can be searched based on key words and phrases over a five-century time frame. Application of the Ngram Viewer to drug literature was assessed for its utility as a research tool. The results appear promising as a method for noting changes in the popularity of specific drugs over time, historical epidemiology of drug use and misuse, and adoption and regulation of drug technologies.


Assuntos
Bases de Dados Factuais , Uso de Medicamentos/tendências , Armazenamento e Recuperação da Informação/métodos , Internet , Ferramenta de Busca , Uso de Medicamentos/estatística & dados numéricos , Literatura Moderna , Uso Indevido de Medicamentos sob Prescrição/estatística & dados numéricos , Uso Indevido de Medicamentos sob Prescrição/tendências
14.
Subst Use Misuse ; 48(1-2): 82-8, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23050592

RESUMO

This study examines the types of tobacco- and smoking-related websites that are available on the Internet. The search terms used were nicotine, tobacco, and cigarette. These terms were searched in the engines Google and Yahoo as well as video-sharing website YouTube and analyzed based on the search engine results pages (SERPs) that were produced. The results returned the following categories of websites: health information and news, smoking cessation, product ads/sales, history of tobacco and smoking, prosmoking/pleasure, smoking prevention/control, and miscellaneous. Results showed fluctuations in the number of search engine results by search term and date. There also was variable quality and availability of informative resources for Internet users due to lack of quality control criteria and regulation.


Assuntos
Serviços de Informação/estatística & dados numéricos , Internet/estatística & dados numéricos , Nicotiana , Fumar , Humanos , Nicotina , Controle de Qualidade , Ferramenta de Busca , Abandono do Hábito de Fumar , Uso de Tabaco
15.
J Am Coll Health ; : 1-9, 2023 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-37167594

RESUMO

Objective: This study focused on purpose as a key mechanism of posttraumatic growth for university student survivors of sexual assault. Participants: An online survey was completed by 278 participants of various ethnic, racial and gender backgrounds, recruited through email, social media, department subject pools, and Amazon Mechanical Turk. Methods: Researchers used mixed methods, concurrent triangulation approach in which quantitative and qualitative data were collected simultaneously with closed and open-ended questions. Results: Hierarchical multiple regression demonstrated that age, purpose in life, high magnitude stressors, and trauma history were significantly related to posttraumatic growth. Emergent themes described the impacts of sexual assault, how sexual assault impacts purpose, and ways in which purpose impacted posttraumatic growth. Conclusion: Results confirmed the association of purpose with posttraumatic growth as well as other key impacts of trauma that should be investigated further. Next steps include evaluating therapeutic interventions focused on purpose.

16.
Ann Work Expo Health ; 67(7): 801-804, 2023 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-37253159

RESUMO

This commentary addresses the post-COVID-19 syndrome and its implications for workers' health. Post-COVID-19 syndrome consists of a set of physiological and psychological symptoms resulting from SARS-CoV-2 (COVID-19) infection, which occur continuously for several weeks or months. Therefore, it is an affectation that has multiple consequences for the recovery of people's health, and compromises the ability to perform daily activities, including work, whether in person or remotely. Although several studies have been published so far, and several long-term consequences on people's health have been demonstrated, most have not adequately delved into the implications for the health of workers, their families, and the socioeconomic cost for governments. The aim of this paper is to highlight this public health issue and to encourage more specialized research.


Assuntos
COVID-19 , Exposição Ocupacional , Humanos , SARS-CoV-2 , Síndrome de COVID-19 Pós-Aguda , Saúde Pública
17.
Dement Neuropsychol ; 16(4): 384-387, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36530763

RESUMO

The Mini-Mental State Examination (MMSE) was created by Marshal Folstein et al. in 1975 as an instrument for brief (5-10 min) assessment of mental status in hospitalized patients. It is considered the most widely used test for standardized cognitive assessment in the clinical setting, especially with the elderly population. It has countless translations in different languages, and according to the different international (PubMed) and regional (SciELO, Redalyc, and Dialnet) scientific databases, it has been widely used by the scientific community. This article describes the historical evolution of the MMSE, highlights its evaluative properties, and provides bibliometric data on its impact on scientific publications, with a special focus on Ibero-America.


El Mini-mental State Examination (MMSE) fue creado por Marshal Folstein et al. en 1975 como un instrumento para la evaluación breve (5-10 minutos) del estado mental de pacientes hospitalizados. Se lo considera la prueba más utilizada para la evaluación cognitiva estandarizada en el ámbito clínico, especialmente con la población adulta mayor. Tiene innumerables traducciones a diferentes idiomas y de acuerdo con las diferentes bases de datos científicas internacionales (PudMed) y regionales (Scielo, Redalyc y Dialnet) se puede constatar que ha sido ampliamente utilizada por la comunidad científica. En este trabajo se describe la evolución histórica del MMSE, se destacan sus propiedades evaluativas y se indican datos bibliométricos acerca de su impacto en las publicaciones científicas, con especial énfasis en IberoAmérica.

18.
Nat Commun ; 13(1): 4785, 2022 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-35970853

RESUMO

Ivosidenib, an inhibitor of isocitrate dehydrogenase 1 (IDH1) R132C and R132H variants, is approved for the treatment of acute myeloid leukaemia (AML). Resistance to ivosidenib due to a second site mutation of IDH1 R132C, leading to IDH1 R132C/S280F, has emerged. We describe biochemical, crystallographic, and cellular studies on the IDH1 R132C/S280F and R132H/S280F variants that inform on the mechanism of second-site resistance, which involves both modulation of inhibitor binding at the IDH1 dimer-interface and alteration of kinetic properties, which enable more efficient 2-HG production relative to IDH1 R132C and IDH1 R132H. Importantly, the biochemical and cellular results demonstrate that it should be possible to overcome S280F mediated resistance in AML patients by using alternative inhibitors, including some presently in phase 2 clinical trials.


Assuntos
Resistencia a Medicamentos Antineoplásicos , Isocitrato Desidrogenase , Leucemia Mieloide Aguda , Resistencia a Medicamentos Antineoplásicos/genética , Glicina/análogos & derivados , Glicina/uso terapêutico , Humanos , Isocitrato Desidrogenase/antagonistas & inibidores , Isocitrato Desidrogenase/genética , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Mutação , Piridinas/uso terapêutico
19.
Subst Use Misuse ; 46(13): 1628-41, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21895517

RESUMO

Antidepressant medications have been the fastest growing category of use of pharmaceutical products over the past decade. Selected Internet web sites providing information on antidepressant medications were identified and assessed using code of conduct criteria for posting health information on the Internet as developed by the Health on the Internet Foundation. Thirteen representative web sites were evaluated. Degree of compliance with each of the eight criterion varied by site, though all 13 sites met the criterion for legality of content and conduct on their web site. WebMD and FamilyDoctor.org met most of the criteria, while pharmaceutical company sites tended to meet the fewest criteria.


Assuntos
Informação de Saúde ao Consumidor/normas , Fidelidade a Diretrizes , Internet , Antidepressivos/uso terapêutico , Informação de Saúde ao Consumidor/métodos , Serviços de Informação sobre Medicamentos/normas , Humanos
20.
Microorganisms ; 9(3)2021 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-33800760

RESUMO

Fruits and vegetables are high in nutrients that are essential for a healthy lifestyle. However, they also harbor an extensive array of microorganisms such as bacteria, which can be beneficial, neutral, or pathogenic. Foodborne pathogens can contaminate produce at any stage from the farm to the consumer's table. Appropriate washing techniques using sanitizers can reduce the risk of pathogen contamination. Issues related to maintaining concentration, efficacy, and other problems have been a challenge for the food industry and, when left unresolved, have led to different outbreaks of foodborne illnesses. In this study, the efficacy of a lytic bacteriophage cocktail was examined for its ability to infect and reduce the contamination of Escherichia coli O157:H7 (E. coli O157:H7), in media with a high organic load, using a microplate technique. The study was conducted for 3 h to determine if the bacteriophage cocktail could reduce the pathogen in the presence of a high organic load. A significant (p < 0.05) reduction in the population of E. coli O157:H7 was observed, representing a 99.99% pathogen reduction at the end of 3 h. Fresh spinach leaves were washed in sterile potable or organic water (~9000 ppm organic load) containing E. coli O157:H7 and a bacteriophage cocktail to study the effectiveness of bacteriophages against the foodborne pathogen. Results indicated that the bacteriophage significantly (p < 0.05) reduced the contamination of E. coli O157:H7 in both situations. The study also demonstrated the bacteriophages' ability to infect and reduce the pathogen in an organic-rich environment. This characteristic differs from commercially available sanitizers that have demonstrated a tendency to bind with the available organic load. Thus, these studies highlight the advantage of employing bacteriophages during produce wash to eliminate foodborne pathogen contamination on fruits and vegetables.

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