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1.
PLoS Biol ; 20(3): e3001548, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35239649

RESUMO

Commitment to cell division at the end of G1 phase, termed Start in the budding yeast Saccharomyces cerevisiae, is strongly influenced by nutrient availability. To identify new dominant activators of Start that might operate under different nutrient conditions, we screened a genome-wide ORF overexpression library for genes that bypass a Start arrest caused by absence of the G1 cyclin Cln3 and the transcriptional activator Bck2. We recovered a hypothetical gene YLR053c, renamed NRS1 for Nitrogen-Responsive Start regulator 1, which encodes a poorly characterized 108 amino acid microprotein. Endogenous Nrs1 was nuclear-localized, restricted to poor nitrogen conditions, induced upon TORC1 inhibition, and cell cycle-regulated with a peak at Start. NRS1 interacted genetically with SWI4 and SWI6, which encode subunits of the main G1/S transcription factor complex SBF. Correspondingly, Nrs1 physically interacted with Swi4 and Swi6 and was localized to G1/S promoter DNA. Nrs1 exhibited inherent transactivation activity, and fusion of Nrs1 to the SBF inhibitor Whi5 was sufficient to suppress other Start defects. Nrs1 appears to be a recently evolved microprotein that rewires the G1/S transcriptional machinery under poor nitrogen conditions.


Assuntos
Fase G1/genética , Regulação Fúngica da Expressão Gênica , Nitrogênio/metabolismo , Fase S/genética , Proteínas de Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/genética , Sequência de Aminoácidos , Divisão Celular/genética , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Immunoblotting , Ligação Proteica , RNA-Seq/métodos , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Homologia de Sequência de Aminoácidos , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
2.
Epilepsy Behav ; 154: 109753, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38636109

RESUMO

PURPOSE: To use a qualitative research approach to explore adults' experience of living with non-epileptic attack disorder. OBJECTIVE: The objective was to explore the experience of adults (18 years+) with a confirmed diagnosis of non-epileptic attack disorder (NEAD) across the trajectory of the disorder. The topics investigated included the onset of symptoms, the experience of non-epileptic attacks, the diagnostic process and living with NEAD. METHOD: Twelve people diagnosed with NEAD who attended a tertiary hospital neurology department took part in semi-structured interviews. The data generated were analysed using reflexive thematic analysis. RESULTS: Eleven women and one man with median age of 25 years took part. Three themes were developed: mind-body (dis)connect, a stigmatised diagnosis and a role for containment. Adults spoke about their experience of nonepileptic attacks, the diagnostic and management process and the impact of both nonepileptic attacks and the NEAD diagnosis on their lives. CONCLUSIONS: Adults' experience's within the healthcare system across the trajectory of NEAD influenced their own understanding and trust in their NEAD experience, how they shared this with others in their social and work lives and how they managed their NEAD symptoms on a daily basis. The research suggests the need for a consistent, timely implementation of a rule-in diagnostic approach and multi-disciplinary management of NEAD. It is recommended that lessons be taken from theoretical models including the common-sense model and a modified version of the reattribution model to support the de-stigmatisation of this diagnosis to inform psychoeducation and professionally facilitated peer-support groups.


Assuntos
Convulsões , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Pesquisa Qualitativa
3.
Telemed J E Health ; 30(4): 1020-1025, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38064483

RESUMO

Background: We evaluated the impact of electronic consultation (eConsult) in reducing the environmental pollutants associated with health care delivery. Methods: A retrospective analysis of the eConsult data between July 2018 and December 2022 was extracted from the electronic health record (Epic). Travel time and mileage from the patient home to the academic medical center (AMC) were calculated along with fuel expenditure and greenhouses gas savings. Projected savings through the end of the decade were forecast using a random walk model. Results: A total of 15,499 eConsults were submitted to AMC specialist providers from community primary care providers. Completed eConsults (n = 11,590) eliminated the need for a face-to-face visit with a specialist provider, eliminating mileage, fuel, time, and pollutants associated with face to face visits. In-state travel distance saved was 310,858 miles, travel time saved was 5,491 h, with an associated fuel reduction of 13,575 gallons and $56,893 savings. This reduced greenhouse gas emissions by 128 metric tons of carbon dioxide, 0.022 tons of nitrogen oxide, 0.005 tons of methane, and 0.001 tons of nitrous oxide. Out of state travel distance saved was 188,346 miles with 2,842 h reduced travel time, and associated fuel reduction of 8,225 gallons and of $34,118. Reduced greenhouse gas emissions were equivalent to 77 metric tons of carbon dioxide, 0.0132 tons of nitrogen oxide, 0.0033 tons of methane, and 0.0007 tons of nitrous oxide. Conclusion: This study indicates that medical care provided through telehealth modalities reduces the environmental impact of pollutants associated with face to face visits.


Assuntos
Poluentes Ambientais , Gases de Efeito Estufa , Consulta Remota , Telemedicina , Humanos , Poluentes Ambientais/análise , Gases de Efeito Estufa/análise , Óxido Nitroso/análise , Estudos Retrospectivos , Dióxido de Carbono/análise , Encaminhamento e Consulta , Centros Médicos Acadêmicos , Viagem , Metano/análise
4.
J Nurs Care Qual ; 39(2): 151-158, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37729000

RESUMO

BACKGROUND: The progression of patients through a hospital from admission to discharge can be slowed by delays in patient discharge, increasing pressure on health care staff. We designed and piloted the Discharge Today tool, with the goal of improving the efficiency of patient discharge; however, adoption remained low. PURPOSE: To close this implementation gap, we deployed and evaluated a 4-part implementation strategy bundle. METHODS: We measured the success of implementation by evaluating validated implementation outcomes using both quantitative and qualitative methods, grounded in Normalization Process Theory. RESULTS: The implementation strategies used were effective for increasing use of the Discharge Today tool by hospital medicine physicians and advanced practice providers during both the active and passive implementation periods. CONCLUSIONS: While the implementation strategies used were effective, qualitative findings indicate that limitations in the functionality of the tool, alongside inconsistent use of the tool across clinical staff, continued to inhibit adoption.


Assuntos
Medicina Hospitalar , Alta do Paciente , Humanos , Pacientes Internados , Hospitalização , Atenção à Saúde
5.
J Med Virol ; 95(2): e28492, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36633204

RESUMO

Mammalian orthoreovirus (MRV) infects many mammalian species including humans, bats, and domestic animals. To determine the prevalence of MRV in bats in the United States, we screened more than 900 bats of different species collected during 2015-2019 by a real-time reverse-transcription polymerase chain reaction assay; 4.4% bats tested MRV-positive and 13 MRVs were isolated. Sequence and phylogenetic analysis revealed that these isolates belonged to four different strains/genotypes of viruses in Serotypes 1 or 2, which contain genes similar to those of MRVs detected in humans, bats, bovine, and deer. Further characterization showed that these four MRV strains replicated efficiently on human, canine, monkey, ferret, and swine cell lines. The 40/Bat/USA/2018 strain belonging to the Serotype 1 demonstrated the ability to infect and transmit in pigs without prior adaptation. Taken together, this is evidence for different genotypes and serotypes of MRVs circulating in US bats, which can be a mixing vessel of MRVs that may spread to other species, including humans, resulting in cross-species infections.


Assuntos
Quirópteros , Cervos , Orthoreovirus de Mamíferos , Orthoreovirus , Animais , Cães , Humanos , Bovinos , Estados Unidos , Suínos , Orthoreovirus de Mamíferos/genética , Filogenia , Furões
6.
Hum Genet ; 141(3-4): 965-979, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34633540

RESUMO

Otosclerosis is a bone disorder of the otic capsule and common form of late-onset hearing impairment. Considered a complex disease, little is known about its pathogenesis. Over the past 20 years, ten autosomal dominant loci (OTSC1-10) have been mapped but no genes identified. Herein, we map a new OTSC locus to a 9.96 Mb region within the FOX gene cluster on 16q24.1 and identify a 15 bp coding deletion in Forkhead Box L1 co-segregating with otosclerosis in a Caucasian family. Pre-operative phenotype ranges from moderate to severe hearing loss to profound sensorineural loss requiring a cochlear implant. Mutant FOXL1 is both transcribed and translated and correctly locates to the cell nucleus. However, the deletion of 5 residues in the C-terminus of mutant FOXL1 causes a complete loss of transcriptional activity due to loss of secondary (alpha helix) structure. FOXL1 (rs764026385) was identified in a second unrelated case on a shared background. We conclude that FOXL1 (rs764026385) is pathogenic and causes autosomal dominant otosclerosis and propose a key inhibitory role for wildtype Foxl1 in bone remodelling in the otic capsule. New insights into the molecular pathology of otosclerosis from this study provide molecular targets for non-invasive therapeutic interventions.


Assuntos
Otosclerose , Fatores de Transcrição Forkhead/genética , Humanos , Otosclerose/genética
7.
MMWR Morb Mortal Wkly Rep ; 71(18): 619-627, 2022 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-35511716

RESUMO

Human rabies is an acute, progressive encephalomyelitis that is nearly always fatal once symptoms begin. Several measures have been implemented to prevent human rabies in the United States, including vaccination of targeted domesticated and wild animals, avoidance of behaviors that might precipitate an exposure (e.g., provoking high-risk animals), awareness of the types of animal contact that require postexposure prophylaxis (PEP), and use of proper personal protective equipment when handling animals or laboratory specimens. PEP is widely available in the United States and highly effective if administered after an exposure occurs. A small subset of persons has a higher level of risk for being exposed to rabies virus than does the general U.S. population; these persons are recommended to receive preexposure prophylaxis (PrEP), a series of human rabies vaccine doses administered before an exposure occurs, in addition to PEP after an exposure. PrEP does not eliminate the need for PEP; however, it does simplify the rabies PEP schedule (i.e., eliminates the need for rabies immunoglobulin and decreases the number of vaccine doses required for PEP). As rabies epidemiology has evolved and vaccine safety and efficacy have improved, Advisory Committee on Immunization Practices (ACIP) recommendations to prevent human rabies have changed. During September 2019-November 2021, the ACIP Rabies Work Group considered updates to the 2008 ACIP recommendations by evaluating newly published data, reviewing frequently asked questions, and identifying barriers to adherence to previous ACIP rabies vaccination recommendations. Topics were presented and discussed during six ACIP meetings. The following modifications to PrEP are summarized in this report: 1) redefined risk categories; 2) fewer vaccine doses in the primary vaccination schedule; 3) flexible options for ensuring long-term protection, or immunogenicity; 4) less frequent or no antibody titer checks for some risk groups; 5) a new minimum rabies antibody titer (0.5 international units [IUs]) per mL); and 6) clinical guidance, including for ensuring effective vaccination of certain special populations.


Assuntos
Profilaxia Pré-Exposição , Vacina Antirrábica , Raiva , Comitês Consultivos , Animais , Humanos , Imunização , Esquemas de Imunização , Imunoglobulinas/uso terapêutico , Raiva/epidemiologia , Raiva/prevenção & controle , Estados Unidos/epidemiologia , Vacinação
8.
Mol Cell Probes ; 64: 101833, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35691598

RESUMO

DNA-based immunization has been previously shown to be an efficient approach to induce robust immunity against infectious diseases in animals and humans. The advantages of DNA vaccines are simplicity of their construction and production, low cost, high stability, and ability to elicit a full spectrum of immune responses to target antigens. The goals of this study were (i) to assess the antibody immune response to rabies virus glycoproteins (rGPs) in rabbits and guinea pigs after intramuscular immunization with pTargeT and pVAC2-mcs mammalian expression vectors encoding either the wild-type (WT) or codon-optimized (cOPT) rGP genes; and (ii) to prepare in-house rabbit anti-rGP polyclonal antibody reagents suitable for in Single Radial Immunodiffusion (SRID) and Indirect Fluorescent Antibody (IFA) assays. The maximum antibody responses against rabies virus in rabbits and guinea pigs were observed after immunization series with 500 µg/dose of pVAC2-mcs vector encoding either the WT or cOPT rGP genes adjuvanted with Emulsigen-D. No significant difference in the anti-rabies virus neutralizing antibody titers was observed in rabbits immunized with the WT and cOPT rGPs. The in-house rabbit anti-rGP polyclonal antibody reagents reacted comparable to the current reference reagents in SRID and IFA assays. The results of the study demonstrated that the DNA immunization of animals with the WT or cOPT rGPs is a promising approach to either induction of high anti-rabies virus neutralizing antibody titers in vivo or for production of polyclonal antibody reagents against rabies.


Assuntos
Vírus da Raiva , Vacinas de DNA , Animais , Anticorpos Neutralizantes , Anticorpos Antivirais , DNA , Glicoproteínas/genética , Cobaias , Imunidade Humoral , Indicadores e Reagentes , Mamíferos/genética , Plasmídeos/genética , Coelhos , Vírus da Raiva/genética , Vacinas de DNA/genética
9.
BMC Pregnancy Childbirth ; 22(1): 660, 2022 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-36002798

RESUMO

BACKGROUND: New mothers experience BF challenges but have limited evidence-based technology-enabled support. OBJECTIVES: 1) Determine if using the Mother's Milk Messaging™ app improved aspects of breastfeeding and breastfeeding rates and 2) Describe engagement as well as themes from the qualitative feedback on the app. METHOD: Randomized Controlled Trial National sample of primiparous, singleton mothers recruited online and then randomized using stratification by language into three arms: 1) BF text messages plus app; 2) BF text messages, app and physician-moderated private Facebook (FB) group; 3) Attention control group who received injury prevention texts. Exclusive breastfeeding rates as primary outcome and knowledge/attitude, confidence, and social support as secondary outcomes. We determined engagement through analysis of app usage metrics. We conducted and content-coded interviews with participants to learn more about app usage and BF experience. Due to the nature of the intervention participants could not be blinded. RESULTS: There were a total of 346 participants in the trial, with 227 in the Intervention (n = 154 group 1 and n = 156 group 2) and 119 in the control group. Because of minimal Facebook activity, the two intervention groups 1 and 2 were combined. There were no differences in breastfeeding exclusivity and duration. (NS). Women in the intervention arm reported significantly higher confidence with breastfeeding and perceived social support to the control group (p < .05). Greater than 80% registered the app and those that engaged with the app had higher scores with time. Mothers appreciated receiving text messages and videos with reliable information. No harm was reported in this study. CONCLUSION: MMM increased confidence with breastfeeding and with gathering social supports. Exclusively BF was high in all participants. Mothers perceived it as useful and dependable especially the texting.


Assuntos
Aplicativos Móveis , Envio de Mensagens de Texto , Aleitamento Materno , Feminino , Humanos , Leite Humano , Mães
10.
BMC Public Health ; 22(1): 1627, 2022 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-36038838

RESUMO

BACKGROUND: Australian Aboriginal and Torres Strait Islander women are at very high risk of violence but there is little evidence about the age at which their higher exposure to violence commences. The aim of this study was to investigate violence inflicted on Aboriginal girls during childhood and adolescence, relative to Aboriginal boys and non-Aboriginal girls. METHODS: This was a retrospective cohort study using de-identified administrative data for NT residents aged 0-17 years. This study used linked hospital and child protection data to investigate hospitalization for injury caused by assault and substantiated child maltreatment involving violence (physical and sexual abuse). RESULTS: The incidence of assault hospitalization and substantiated physical/sexual abuse was much higher for Aboriginal than non-Aboriginal adolescents but similar for girls and boys to about age ten, then increased much more for Aboriginal girls than boys. In the 14-17 age-group, assault hospitalization incidence was 125% higher for Aboriginal girls than boys but 56% lower for non-Aboriginal girls than boys. 4.6% of Aboriginal girls were hospitalized (30.9% more than once) for assault between twelfth and eighteenth birthdays, compared to 3.4% of Aboriginal boys and 0.3% of non-Aboriginal girls. The incidence of assault hospitalization during adolescence was over three times higher for Aboriginal children who had substantiated child maltreatment during childhood. CONCLUSION: The very high levels of violence suffered by Aboriginal women commence in the pre-teen years. Non-Aboriginal girls are 'protected' from the rising levels of violence that boys experience as they progress through adolescence, but Aboriginal girls are not afforded such protection.


Assuntos
Maus-Tratos Infantis , Havaiano Nativo ou Outro Ilhéu do Pacífico , Adolescente , Criança , Feminino , Humanos , Masculino , Northern Territory/epidemiologia , Estudos Retrospectivos , Violência
11.
J Med Internet Res ; 24(4): e32825, 2022 04 22.
Artigo em Inglês | MEDLINE | ID: mdl-35451978

RESUMO

BACKGROUND: Sleep disturbances and poor health-related quality of life (HRQoL) are common in people with rheumatoid arthritis (RA). Sleep disturbances, such as less total sleep time, more waking periods after sleep onset, and higher levels of nonrestorative sleep, may be a driver of HRQoL. However, understanding whether these sleep disturbances reduce HRQoL has, to date, been challenging because of the need to collect complex time-varying data at high resolution. Such data collection is now made possible by the widespread availability and use of mobile health (mHealth) technologies. OBJECTIVE: This mHealth study aimed to test whether sleep disturbance (both absolute values and variability) causes poor HRQoL. METHODS: The quality of life, sleep, and RA study was a prospective mHealth study of adults with RA. Participants completed a baseline questionnaire, wore a triaxial accelerometer for 30 days to objectively assess sleep, and provided daily reports via a smartphone app that assessed sleep (Consensus Sleep Diary), pain, fatigue, mood, and other symptoms. Participants completed the World Health Organization Quality of Life-Brief (WHOQoL-BREF) questionnaire every 10 days. Multilevel modeling tested the relationship between sleep variables and the WHOQoL-BREF domains (physical, psychological, environmental, and social). RESULTS: Of the 268 recruited participants, 254 were included in the analysis. Across all WHOQoL-BREF domains, participants' scores were lower than the population average. Consensus Sleep Diary sleep parameters predicted the WHOQoL-BREF domain scores. For example, for each hour increase in the total time asleep physical domain scores increased by 1.11 points (ß=1.11, 95% CI 0.07-2.15) and social domain scores increased by 1.65 points. These associations were not explained by sociodemographic and lifestyle factors, disease activity, medication use, anxiety levels, sleep quality, or clinical sleep disorders. However, these changes were attenuated and no longer significant when pain, fatigue, and mood were included in the model. Increased variability in total time asleep was associated with poorer physical and psychological domain scores, independent of all covariates. There was no association between actigraphy-measured sleep and WHOQoL-BREF. CONCLUSIONS: Optimizing total sleep time, increasing sleep efficiency, decreasing sleep onset latency, and reducing variability in total sleep time could improve HRQoL in people with RA.


Assuntos
Artrite Reumatoide , Transtornos do Sono-Vigília , Telemedicina , Adulto , Artrite Reumatoide/complicações , Fadiga , Humanos , Dor , Estudos Prospectivos , Qualidade de Vida/psicologia , Sono , Inquéritos e Questionários
12.
J Med Internet Res ; 23(9): e28797, 2021 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-34528888

RESUMO

BACKGROUND: Although patient portals are widely used for health promotion, little is known about the use of palliative care and end-of-life (PCEOL) portal tools available for patients and caregivers. OBJECTIVE: This study aims to identify and assess the user perspectives of PCEOL portal tools available to patients and caregivers described and evaluated in the literature. METHODS: We performed a scoping review of the academic literature directed by the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) extension for Scoping Review and searched three databases. Sources were included if they reported the development or testing of a feature, resource, tool, or intervention; focused on at least one PCEOL domain defined by the National Coalition for Hospice and Palliative Care; targeted adults with serious illness or caregivers; and were offered via a patient portal tethered to an electronic medical record. We independently screened the titles and abstracts (n=796) for eligibility. Full-text (84/796, 10.6%) sources were reviewed. We abstracted descriptions of the portal tool name, content, targeted population, and reported user acceptability for each tool from included sources (n=19). RESULTS: In total, 19 articles describing 12 tools were included, addressing the following PCEOL domains: ethical or legal (n=5), physical (n=5), and psychological or psychiatric (n=2). No tools for bereavement or hospice care were identified. Studies have reported high acceptability of tools among users; however, few sources commented on usability among older adults. CONCLUSIONS: PCEOL patient portal tools are understudied. As medical care increasingly moves toward virtual platforms, future research should investigate the usability and acceptability of PCEOL patient portal resources and evaluate their impact on health outcomes.


Assuntos
Cuidados Paliativos na Terminalidade da Vida , Portais do Paciente , Assistência Terminal , Idoso , Cuidadores , Humanos , Cuidados Paliativos
13.
Health Promot Pract ; 22(6): 850-862, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-32698702

RESUMO

One crucial factor that leads to disparities in smoking cessation between groups with higher and lower socioeconomic status is more prevalent socioenvironmental smoking cues in low-income communities. Little is known about how these cues influence socioeconomically disadvantaged smokers in real-world scenarios and how to design interventions, especially mobile phone-based interventions, to counteract the impacts of various types of smoking cues. We interviewed 15 current smokers living in low-income communities and scanned their neighborhoods to explore smoking-related experiences and identify multilevel cues that may trigger them to smoke. Findings suggest four major types of smoking cues influence low-income smokers-internal, habitual, social, and environmental. We propose an ecological model of smoking cues to inform the design of mobile health (mHealth) interventions for smoking cessation. We suggest that user-triggered strategies will be most useful to address internal cues; server-triggered strategies will be most suitable in changing perceived social norms of smoking and routine smoking activities to address social and habitual cues; and context-triggered strategies will be most effective for counteracting environmental cues. The pros and cons of each approach are discussed regarding their cost-effectiveness, the potential to provide personalized assistance, and scale.


Assuntos
Fumantes , Telemedicina , Sinais (Psicologia) , Humanos , Projetos Piloto , Fumar
14.
Pediatr Res ; 87(2): 277-281, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31330527

RESUMO

Vaccine-preventable infections (VPIs) are a common and serious complication following transplantation. One in six pediatric solid organ transplant recipients is hospitalized with a VPI in the first 5 years following transplant and these hospitalizations result in significant morbidity, mortality, graft injury, and cost. Immunizations are a minimally invasive, cost-effective approach to reducing the incidence of VPIs. Despite published recommendations for transplant candidates to receive all age-appropriate immunizations, under-immunization remains a significant problem, with the majority of transplant recipients not up-to-date on age-appropriate immunizations at the time of transplant. This is extremely concerning as the rate for non-medical vaccine exemptions in the United States (US) is increasing, decreasing the reliability of herd immunity to protect patients undergoing transplant from VPIs. There is an urgent need to better understand barriers to vaccinating this population of high-risk children and to develop effective interventions to overcome these barriers and improve immunization rates. Strengthened national policies requiring complete age-appropriate immunization for non-emergent transplant candidates, along with improved multi-disciplinary immunization practices and tools to facilitate and ensure complete immunization delivery to this high-risk population, are needed to ensure that we do everything possible to prevent infectious complications in pediatric transplant recipients.


Assuntos
Hospedeiro Imunocomprometido , Imunossupressores/uso terapêutico , Infecções Oportunistas/prevenção & controle , Transplante de Órgãos/tendências , Pediatria/tendências , Vacinação/tendências , Doenças Preveníveis por Vacina/prevenção & controle , Fatores Etários , Humanos , Imunossupressores/efeitos adversos , Incidência , Infecções Oportunistas/epidemiologia , Infecções Oportunistas/imunologia , Transplante de Órgãos/efeitos adversos , Medição de Risco , Fatores de Risco , Doenças Preveníveis por Vacina/epidemiologia , Doenças Preveníveis por Vacina/imunologia
15.
MMWR Morb Mortal Wkly Rep ; 69(38): 1374-1377, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32970659

RESUMO

Although canine rabies virus variant (CRVV) was successfully eliminated from the United States after approximately 6 decades of vaccination campaigns, licensing requirements, and stray animal control, dogs remain the principal source of human rabies infections worldwide. A rabies vaccination certificate is required for dogs entering the United States from approximately 100 countries with endemic CRVV, including Egypt (1). On February 25, 2019, rabies was diagnosed in a dog imported from Egypt, representing the third canine rabies case imported from Egypt in 4 years (2,3). This dog and 25 others were imported by a pet rescue organization in the Kansas City metropolitan area on January 29. Upon entry into the United States, all 26 dogs had certificates of veterinary inspection, rabies vaccination certificates, and documentation of serologic conversion from a government-affiliated rabies laboratory in Egypt. CDC confirmed that the dog was infected with a CRVV that circulates in Egypt, underscoring the continued risk for CRVV reintroduction and concern regarding the legitimacy of vaccine documentation of dogs imported from countries considered at high risk for CRVV. Vaccination documentation of dogs imported from these countries should be critically evaluated before entry into the United States is permitted, and public health should be consulted upon suspicion of questionable documents.


Assuntos
Doenças Transmissíveis Importadas/veterinária , Doenças do Cão/diagnóstico , Raiva/veterinária , Animais , Doenças Transmissíveis Importadas/diagnóstico , Cães , Egito , Kansas , Raiva/diagnóstico
16.
Nature ; 502(7470): 232-6, 2013 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-23934107

RESUMO

The blood system is maintained by a small pool of haematopoietic stem cells (HSCs), which are required and sufficient for replenishing all human blood cell lineages at millions of cells per second throughout life. Megakaryocytes in the bone marrow are responsible for the continuous production of platelets in the blood, crucial for preventing bleeding--a common and life-threatening side effect of many cancer therapies--and major efforts are focused at identifying the most suitable cellular and molecular targets to enhance platelet production after bone marrow transplantation or chemotherapy. Although it has become clear that distinct HSC subsets exist that are stably biased towards the generation of lymphoid or myeloid blood cells, we are yet to learn whether other types of lineage-biased HSC exist or understand their inter-relationships and how differently lineage-biased HSCs are generated and maintained. The functional relevance of notable phenotypic and molecular similarities between megakaryocytes and bone marrow cells with an HSC cell-surface phenotype remains unclear. Here we identify and prospectively isolate a molecularly and functionally distinct mouse HSC subset primed for platelet-specific gene expression, with enhanced propensity for short- and long-term reconstitution of platelets. Maintenance of platelet-biased HSCs crucially depends on thrombopoietin, the primary extrinsic regulator of platelet development. Platelet-primed HSCs also frequently have a long-term myeloid lineage bias, can self-renew and give rise to lymphoid-biased HSCs. These findings show that HSC subtypes can be organized into a cellular hierarchy, with platelet-primed HSCs at the apex. They also demonstrate that molecular and functional priming for platelet development initiates already in a distinct HSC population. The identification of a platelet-primed HSC population should enable the rational design of therapies enhancing platelet output.


Assuntos
Plaquetas/citologia , Diferenciação Celular , Células-Tronco Hematopoéticas/citologia , Animais , Linhagem da Célula/genética , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Transplante de Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas/metabolismo , Linfócitos/citologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL
17.
Clin Infect Dis ; 66(3): 387-395, 2018 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-29020321

RESUMO

Background: Lack of access to rabies immunoglobulin (RIG) contributes to high rabies mortality. A recombinant human monoclonal antibody (SII RMAb) was tested in a postexposure prophylaxis (PEP) regimen in comparison with a human RIG (HRIG)-containing PEP regimen. Methods: This was a phase 2/3, randomized, single-blind, noninferiority study conducted in 200 participants with World Health Organization category III suspected rabies exposures. Participants received either SII RMAb or HRIG (1:1 ratio) in wounds and, if required, intramuscularly on day 0, along with 5 doses of rabies vaccine intramuscualarly on days 0, 3, 7, 14 and 28. The primary endpoint was the ratio of the day 14 geometric mean concentration (GMC) of rabies virus neutralizing activity (RVNA) as measured by rapid fluorescent focus inhibition test for SII RMAb recipients relative to HRIG recipients. Results: One hundred ninety-nine participants received SII RMAb (n = 101) or HRIG (n = 98) and at least 1 dose of vaccine. The day 14 GMC ratio of RVNA for the SII RMAb group relative to the HRIG group was 4.23 (96.9018% confidence interval [CI], 2.59-6.94) with a GMC of of 24.90 IU/mL (95% CI, 18.94-32.74) for SII RMAb recipients and 5.88 IU/mL (95% CI, 4.11-8.41) for HRIG recipients. The majority of local injection site and systemic adverse reactions reported from both groups were mild to moderate in severity. Conclusions: A PEP regimen containing SII RMAb was safe and demonstrated noninferiority to HRIG PEP in RVNA production. The novel monoclonal potentially offers a safe and potent alternative for the passive component of PEP and could significantly improve the management of bites from suspected rabid animals. Clincical Trials Registration: CTRI/2012/05/002709.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/administração & dosagem , Profilaxia Pós-Exposição/métodos , Raiva/prevenção & controle , Adulto , Anticorpos Antivirais/sangue , Mordeduras e Picadas/virologia , Feminino , Humanos , Injeções Intramusculares , Masculino , Pessoa de Meia-Idade , Vacina Antirrábica/administração & dosagem , Vírus da Raiva , Método Simples-Cego
19.
Matern Child Health J ; 22(11): 1589-1597, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29936658

RESUMO

Objective This qualitative study explored parent and patient navigator perspectives of home visitation as part of a childhood obesity program in a low-income, largely Latino population. Methods Three patient navigators and 25 parents who participated in a home-based, childhood obesity program participated in focus groups or interviews. Emergent themes were identified through content analysis of qualitative data. Results Three overall themes were identified. Patient navigators and parents perceived: (1) enabling characteristics of home-based program delivery which facilitated family participation and/or behavior change (i.e., convenience, increased accountability, inclusion of household members, delivery in a familiar, intimate setting, and individualized pace and content); (2) logistic and cultural challenges to home-based delivery which reduced family participation and program reach (i.e., difficulties scheduling visits, discomfort with visitors in the home, and confusion about the patient navigator's role); and (3) remediable home-based delivery challenges which could be ameliorated by additional study staff (e.g., supervision of children, safety concerns) or through organized group sessions. Both patient navigators and participating parents discussed an interest in group classes with separate, supervised child-targeted programming and opportunities to engage with other families for social support. Conclusions for Practice A home visitation program delivering a pediatric obesity prevention curriculum in Denver was convenient and held families accountable, but posed scheduling difficulties and raised safety concerns. Conducting home visits in pairs, adding obesity prevention curriculum to existing home visiting programs, or pairing the convenience of home visits with group classes may be future strategies to explore.


Assuntos
Exercício Físico , Hispânico ou Latino/estatística & dados numéricos , Visita Domiciliar , Avaliação de Processos e Resultados em Cuidados de Saúde , Poder Familiar , Navegação de Pacientes/organização & administração , Obesidade Infantil/etnologia , Obesidade Infantil/terapia , Índice de Massa Corporal , Pré-Escolar , Colorado , Dieta , Feminino , Hispânico ou Latino/psicologia , Humanos , Masculino , Sobrepeso/etnologia , Sobrepeso/terapia , Avaliação de Programas e Projetos de Saúde , Pesquisa Qualitativa
20.
Risk Anal ; 38(4): 839-852, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28768045

RESUMO

In the 1930s, Heinrich established one of the most prominent and enduring accident prevention theories when he concluded that high severity occupational safety and health (OSH) incidents are preceded by numerous lower severity incidents and near misses. Seventy-five years of theory expansion/interpretation includes two fundamental tenets: (1) the ratio of lower to higher severity incidents exists in the form of a "safety-triangle" and (2) similar causes underlie both high and low severity events. Although used extensively to inform public policy and establishment-level health and safety priorities, recent research challenges the validity of the two tenets. This study explored the validity of the first tenet, the existence of the safety triangle. The advantage of the current study is the use of a detailed, establishment-specific data set that evaluated over 25,000 establishments over a 13-year time period, allowing three specific questions to be explored: (1) Are an increased number of lower severity incidents at an establishment significantly associated with the probability of a fatal event over time? (2) At the establishment level, do the effects of OSH incidents on the probability of a fatality over time decrease as the degree of severity decreases-thereby taking the form of a triangle? and (3) Do distinct methods for delineating incidents by severity affect the existence of the safety triangle form? The answer to all three questions was yes with the triangle form being dependent upon how severity was delineated. The implications of these findings in regard to Heinrich's theory and OSH policy and management are discussed.

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