RESUMO
Mammalian glucose homeostasis is, in part, nutritionally programmed during early neonatal life, a critical window for the formation of synapses between hypothalamic glucoregulatory centers. Although microglia are known to prune synapses throughout the brain, their specific role in refining hypothalamic glucoregulatory circuits remains unknown. Here, we show that microglia in the mediobasal hypothalamus (MBH) of mice actively engage in synaptic pruning during early life. Microglial phagocytic activity is induced following birth, regresses upon weaning from maternal milk, and is exacerbated by feeding dams a high-fat diet while lactating. In particular, we show that microglia refine perineuronal nets (PNNs) within the neonatal MBH. Indeed, transiently depleting microglia before weaning (P6-16), but not afterward (P21-31), remarkably increased PNN abundance in the MBH. Furthermore, mice lacking microglia only from P6-16 had glucose intolerance due to impaired glucose-responsive pancreatic insulin secretion in adulthood, a phenotype not seen if microglial depletion occurred after weaning. Viral retrograde tracing revealed that this impairment is linked to a reduction in the number of neurons in specific hypothalamic glucoregulatory centers that synaptically connect to the pancreatic ß-cell compartment. These findings show that microglia facilitate synaptic plasticity in the MBH during early life through a process that includes PNN refinement, to establish hypothalamic circuits that regulate adult glucose homeostasis.
Assuntos
Adalimumab/efeitos adversos , Doença de Crohn/tratamento farmacológico , Infecção Latente/induzido quimicamente , Tuberculose Latente/diagnóstico , Tuberculose dos Linfonodos/diagnóstico , Adalimumab/uso terapêutico , Anti-Inflamatórios/efeitos adversos , Anti-Inflamatórios/uso terapêutico , Antituberculosos/administração & dosagem , Antituberculosos/uso terapêutico , Doença de Crohn/complicações , Humanos , Hospedeiro Imunocomprometido/imunologia , Tuberculose Latente/tratamento farmacológico , Tuberculose Latente/etiologia , Masculino , Pessoa de Meia-Idade , Tuberculose dos Linfonodos/tratamento farmacológico , Tuberculose dos Linfonodos/etiologiaAssuntos
Vírus da Influenza B , Influenza Humana/virologia , Estações do Ano , Antivirais/uso terapêutico , Humanos , Hospedeiro Imunocomprometido , Influenza Humana/tratamento farmacológico , Lúpus Eritematoso Sistêmico , Masculino , Oseltamivir/uso terapêutico , Viagem , Resultado do Tratamento , Adulto JovemRESUMO
Individuals 65 years or older will comprise an estimated 20.0% of the U.S. population by 2030. This study investigated the association between food insecurity and health-related quality of life (HRQoL) among an older adult population (n = 234). HRQoL was measured using Healthy Days, a validated survey tool developed by the Centers of Disease Control and Prevention. Food-insecure individuals were more likely to report ≥14 physically unhealthy days (OR = 1.49, 95% CI 0.47-4.78) and ≥14 days with activity limitations (OR = 4.07, 95% CI 0.68-24.1). Although nonsignificant, the findings highlight food insecurity as a potentially important social determinant of health throughout the life course, including at an older age.
Assuntos
Abastecimento de Alimentos , Qualidade de Vida , Idoso , Análise de Variância , Distribuição de Qui-Quadrado , Estudos Transversais , Escolaridade , Emprego , Feminino , Florida , Abastecimento de Alimentos/economia , Abastecimento de Alimentos/estatística & dados numéricos , Humanos , Renda , Modelos Logísticos , Masculino , Apoio Social , Fatores SocioeconômicosRESUMO
Dietary supplements are increasingly popular in Irish society. One of these is blue-green algae which is used with a variety health benefits in mind. A batch of Chlorella powder was found to be contaminated with Salmonella species in Ireland in 2015. This prompted additional testing of a total of 8 samples of three different products (Chlorella, Spirulina and Super Greens), for other faecal flora and antimicrobial resistance in any bacteria isolated. All 8 samples cultured enteric flora such as Enterococci, Enterobacteriaceae and Clostridium species. Antimicrobial susceptibility testing revealed one isolate with extended-spectrum ?-lactamase (ESBL) activity and one with carbapenemase activity. Clinicians caring for vulnerable patients should be aware of the potential risk of exposure to antimicrobial resistant bacteria associated with these products.
Assuntos
Chlorella/microbiologia , Suplementos Nutricionais/microbiologia , Farmacorresistência Bacteriana , Fezes/microbiologia , Spirulina , Clostridium/efeitos dos fármacos , Clostridium/isolamento & purificação , Enterobacteriaceae/efeitos dos fármacos , Enterobacteriaceae/isolamento & purificação , Enterococcus faecalis/efeitos dos fármacos , Enterococcus faecalis/isolamento & purificação , Humanos , IrlandaRESUMO
Blood and marrow transplantation (BMT) is a complex and evolving medical speciality that makes substantial demands on healthcare resources. To meet a professional responsibility to both patients and public health services, the European Society for Blood and Marrow Transplantation (EBMT) initiated and developed the Joint Accreditation Committee of the International Society for Cellular Therapy and EBMT-better known by the acronym, JACIE. Since its inception, JACIE has performed over 530 voluntary accreditation inspections (62% first time; 38% reaccreditation) in 25 countries, representing 40% of transplant centres in Europe. As well as widespread professional acceptance, JACIE has become incorporated into the regulatory framework for delivery of BMT and other haematopoietic cellular therapies in several countries. In recent years, JACIE has been validated using the EBMT registry as an effective means of quality improvement with a substantial positive impact on survival outcomes. Future directions include development of Europe-wide risk-adjusted outcome benchmarking through the EBMT registry and further extension beyond Europe, including goals to faciliate access for BMT programmes in in low- and middle-income economies (LMIEs) via a 'first-step' process.
Assuntos
Acreditação , Transfusão de Sangue , Transplante de Medula Óssea , Modelos Teóricos , Qualidade da Assistência à Saúde , Europa (Continente) , Feminino , Humanos , MasculinoRESUMO
In 2013, recommendations for a standardized practice in the prophylaxis and treatment of GvHD were adopted and published by the European Society for Blood and Marrow Transplantation and the European LeukemiaNet. One year later, all 341 European Society for Blood and Marrow Transplantation centres performing allogeneic haematopoietic stem cell transplantation were contacted for a change-control analysis and asked to fill in a questionnaire; 111 centres (33%) responded. Of these, 83% had been aware of the recommendations. Paediatric centres (P=0.004), centres with shorter programme duration (P=0.049), not JACIE (the Joint Accreditation Committee of the International Society for Cellular Therapy and the European Society for Blood and Marrow Transplantation)-accredited centres (P=0.010) and centres from middle-income countries (P=0.033) were more likely to be unaware of the recommendations. Thirty-eight per cent of the centres regarded the recommendations as relevant guidelines affecting their policies, 61% as interesting information. Thirty per cent had decided to make changes in their institutional protocols based on the recommendations. More than 80% were willing to use the recommendations for a control arm in randomized studies. This survey shows that the published recommendations had some, though insufficient, impact on the strategies and methods of allogeneic haematopoietic stem cell transplantation applied by the centres. It also identified some of the weaknesses to be addressed when releasing recommendations in the future.
Assuntos
Doença Enxerto-Hospedeiro/prevenção & controle , Fidelidade a Diretrizes , Transplante de Células-Tronco Hematopoéticas , Adolescente , Adulto , Aloenxertos , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Guias de Prática Clínica como AssuntoRESUMO
BACKGROUND: Carbapenemase-producing Enterobacteriaceae (CPE) may cause healthcare-associated infections with high mortality rates. New Delhi metallo-ß-lactamase-1 (NDM-1) is among the most recently discovered carbapenemases. AIM: To report the first outbreak of NDM-1 CPE in Ireland, including microbiological and epidemiological characteristics, and assessing the impact of infection prevention and control measures. METHODS: This was a retrospective microbiological and epidemiological review. Cases were defined as patients with a CPE-positive culture. Contacts were designated as roommates or ward mates. FINDINGS: This outbreak involved 10 patients with a median age of 71 years (range: 45-90), located in three separate but affiliated healthcare facilities. One patient was infected (the index case); the nine others were colonized. Nine NDM-1-producing Klebsiella pneumoniae, an NDM-1-producing Escherichia coli and a K. pneumoniae carbapenemase (KPC)-producing Enterobacter cloacae were detected between week 24, 2014 and week 37, 2014. Pulsed-field gel electrophoresis demonstrated similarity. NDM-1-positive isolates were meropenem resistant with minimum inhibitory concentrations (MICs) ranging from 12 to 32 µg/mL. All were tigecycline susceptible (MICs ≤1 µg/mL). One isolate was colistin resistant (MIC 4.0 µg/mL; mcr-1 gene not detected). In 2015, four further NDM-1 isolates were detected. CONCLUSION: The successful management of this outbreak was achieved via the prompt implementation of enhanced infection prevention and control practices to prevent transmission. These patients did not have a history of travel outside of Ireland, but several had frequent hospitalizations in Ireland, raising concerns regarding the possibility of increasing but unrecognized prevalence of NDM-1 and potential decline in value of travel history as a marker of colonization risk.
Assuntos
Portador Sadio/epidemiologia , Surtos de Doenças , Infecções por Enterobacteriaceae/epidemiologia , Enterobacteriaceae/enzimologia , beta-Lactamases/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Portador Sadio/microbiologia , Transmissão de Doença Infecciosa/prevenção & controle , Eletroforese em Gel de Campo Pulsado , Enterobacteriaceae/classificação , Enterobacteriaceae/genética , Enterobacteriaceae/isolamento & purificação , Infecções por Enterobacteriaceae/microbiologia , Feminino , Humanos , Controle de Infecções/métodos , Irlanda/epidemiologia , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Tipagem Molecular , Prevalência , Estudos RetrospectivosRESUMO
In October 2012, an outbreak of gentamicin-resistant, ciprofloxacin non-susceptible extended-spectrum ß-lactamase (ESBL)-producing Klebsiella pneumoniae occurred in a neonatal intensive care unit in Ireland. In order to determine whether the outbreak strain was more widely dispersed in the country, 137 isolates of K. pneumoniae with this resistance phenotype collected from 17 hospitals throughout Ireland between January 2011 and July 2013 were examined. ESBL production was confirmed phenotypically and all isolates were screened for susceptibility to 19 antimicrobial agents and for the presence of genes encoding bla TEM, bla SHV, bla OXA, and bla CTX-M; 22 isolates were also screened for bla KPC, bla NDM, bla VIM, bla IMP and bla OXA-48 genes. All isolates harboured bla SHV and bla CTX-M and were resistant to ciprofloxacin, gentamicin, nalidixic acid, amoxicillin-clavulanate, and cefpodoxime; 15 were resistant to ertapenem, seven to meropenem and five isolates were confirmed as carbapenemase producers. Pulsed-field gel electrophoresis of all isolates identified 16 major clusters, with two clusters comprising 61% of the entire collection. Multilocus sequence typing of a subset of these isolates identified a novel type, ST1236, a single locus variant of ST48. Data suggest that two major clonal groups, ST1236/ST48 (CG43) and ST15/ST14 (CG15) have been circulating in Ireland since at least January 2011.
Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla , Infecções por Klebsiella/epidemiologia , Klebsiella pneumoniae/classificação , Klebsiella pneumoniae/efeitos dos fármacos , Eletroforese em Gel de Campo Pulsado , Irlanda/epidemiologia , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/isolamento & purificaçãoRESUMO
INTRODUCTION: Patient information leaflets (PILs) are an important source of information for patients postoperatively. There are currently no nationally agreed standards by dermatologists for postoperative advice following skin surgery. AIM: To assess the common themes and areas of variation in advice given in PILs after skin surgery across all National Health Service (NHS) hospitals in England and Wales. METHODS: All acute trusts in England (n = 159) and local health boards in Wales (n = 7) were requested to provide their postoperative dermatological PILs for general sutured wound care or excision biopsy. Eight preselected parameters were assessed: minimum dressing duration, duration of pressing on a bleeding wound, postoperative analgesia, explanation of infection signs, application of petroleum jelly, scarring, whom to contact if there is a problem, and the recommended postoperative time for abstaining from active exercise. RESULTS: PILs were received from 137 different dermatology departments belonging to 127/166 (76.5%) organisations across England and Wales. Of these, 102 PILs gave a specific duration for dressings: 45/102 (44.1%) advised a minimum of 48 h, but 28/102 (27.5%) recommended leaving dressings in place until suture removal. Regarding duration of pressing on a bleeding wound, 117 PILs gave advice, with the most common recommendation being 15 min (30/117, 25.6%), followed closely by 10 min (26/117, 22.2%). Of the 137 PILs received, 125 gave advice regarding postoperative analgesia, with paracetamol alone being the most common recommendation (24/125, 19.2%). For the remaining parameters, 111/137 (81.0%) PILs described ≥ 2 signs of infection, 42/137 (30.7%) recommended the application of petroleum jelly, 65/137 (47.4%) mentioned scarring, 137/137 (100%) highlighted whom to contact if there were postoperative problems and 87/137 (63.5%) PILs gave advice regarding postoperative abstinence from active exercise. CONCLUSIONS: The advice given in dermatology postoperative PILs across England and Wales is highly variable. A nationally agreed template or set of postoperative advice should be considered to improve consistency.
Assuntos
Dor Pós-Operatória/terapia , Folhetos , Educação de Pacientes como Assunto , Cuidados Pós-Operatórios/métodos , Dermatopatias/cirurgia , Analgesia/métodos , Bandagens , Inglaterra , Letramento em Saúde , Humanos , Dor Pós-Operatória/prevenção & controle , Educação de Pacientes como Assunto/métodos , Educação de Pacientes como Assunto/normas , Medicina Estatal , País de GalesRESUMO
INTRODUCTION: Since 2000 a decline in the incidence of occupational asthma (OA) has been reported in the UK and Europe. We aimed to describe and account for trends in the incidence of OA in the West Midlands, UK using annual notification data from the SHIELD voluntary surveillance scheme over the period 1991-2011. METHODS: All notifications to the SHIELD database between January 1991 and December 2011 were identified, along with patients' demographic data, occupations, causative agents and confirmatory tests. Annual notifications were scaled to give an annual count per million workers, giving a measure of incidence, and also standardised against those of bakers' asthma. Non-parametric analyses were undertaken between annual incidence and time (years) for common causative agents using (1) a negative binomial regression univariate model and (2) a logistic regression model calculating annual reporting ORs. A step-change analysis was used to examine time points at which there were marked reductions in incidence. RESULTS: A decrease in annual incidence of OA was observed over the study period (incident rate ratio=0.945; 95% CI 0.933 to 0.957; p<0.0001), an effect that was lost after standardising for bakers' asthma. Decreases in incidence were seen for most common causative agents, with only cleaning product-related OA increasing over 21â years. Marked fall in incidence was seen in 2004 for isocyanates, and in 1995 for latex. Most notifications came from a regional specialist occupational lung disease unit, with notifications from other sites falling from 16 cases/million workers/annum in 1995 to 0 in 2004. CONCLUSIONS: Reporter fatigue and increasing under-recognition of OA are both factors which contribute to the apparent fall in incidence of OA in the West Midlands. There is a future need for interventions that enable health professionals to identify potential cases of OA in the workplace and in healthcare settings.
Assuntos
Asma Ocupacional/epidemiologia , Asma Ocupacional/prevenção & controle , Vigilância da População , Adulto , Surtos de Doenças , Inglaterra/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-IdadeRESUMO
Obtaining a reliable venous access is a limiting factor for early initiation of clotting factor prophylaxis and immune tolerance induction. To circumvent this issue, central venous access devices (CVADs) are increasingly being used. Catheter-related infections (CRIs) remain the primary complication of insertion of CVAD. Thus, newer strategies for treatment and prevention of CRI are needed. Ethanol lock therapy (ELT) has been used to treat and prevent CRI in non-bleeding disorder patients. The aim of this study was to assess the efficacy of ELT in treating and preventing CRI in bleeding disorder patients. The medical charts of patients with bleeding disorders who underwent ELT for antimicrobial resistant CRIs were reviewed and data were analysed. ELT was effective in catheter salvage in 87% of patients with antimicrobial resistant CRI by a wide variety of pathogens. Prophylactic therapy with ethanol lock was associated with catheter dysfunction especially in mediports. ELT should be considered prior to removal of catheters in bleeding disorder patients with resistant CRIs. Further studies are needed for using prophylactic ethanol lock in prevention of CRIs in bleeding disorder patients.
Assuntos
Anti-Infecciosos/administração & dosagem , Antibioticoprofilaxia , Transtornos da Coagulação Sanguínea/complicações , Infecções Relacionadas a Cateter/tratamento farmacológico , Infecções Relacionadas a Cateter/etiologia , Etanol/administração & dosagem , Transtornos da Coagulação Sanguínea/diagnóstico , Infecções Relacionadas a Cateter/prevenção & controle , Cateteres de Demora/efeitos adversos , Humanos , Masculino , Resultado do TratamentoRESUMO
BACKGROUND: Using mixed-methods research, we investigated whether the adult version of the WHOQOL-BREF was acceptable and feasible to use with adolescents (13-19), and what features might need to be changed to develop it. Differences from young adults quality of life (QoL) (20-30 years) could add justification. METHODS: Preliminary psychometric properties of the adult WHOQOL-BREF were examined in 208 adolescents and 204 young adults. Unhealthy adolescents diagnosed with acne or elevated depressive symptoms (CES-D) were compared with healthy adolescents. Cognitive interviewing used 'think aloud' techniques with six healthy adolescents during WHOQOL-BREF completion. Concepts and wording were thematically analysed for relevance, comprehension and comprehensiveness. RESULTS: Little data were missing from the WHOQOL-BREF suggesting some feasibility and acceptability to adolescents. Compared with adults, adolescents perceived greater access to information, a better home environment, worse pain, and medication dependency. Internal consistency reliability for adolescents was good (α = .89), especially psychological and environmental QoL. Content validity especially for social and environment domains was supported. Domains validly discriminated between high- and low-depressive symptoms but not acne groups. Additional new facets on autonomy, altruism and physical fitness and changed item contents are proposed. CONCLUSION: The evidence indicates that developing a new adolescent version is justifiable. Cross-cultural research should build on these preliminary findings.
Assuntos
Qualidade de Vida/psicologia , Inquéritos e Questionários , Adolescente , Adulto , Estudos de Casos e Controles , Estudos de Viabilidade , Feminino , Humanos , Masculino , Psicometria , Reprodutibilidade dos Testes , Adulto JovemRESUMO
We report the first case in Ireland of an IMI-1 carbapenemase-producing Enterobacter asburiae, which was resistant to both colistin and fosfomycin. The circumstances under which this isolate was acquired were unclear. Several reports of IMI-producing Enterobacter spp. have emerged in recent years, and colistin resistance in Enterobacteriaceae is also increasingly reported. Laboratories should be aware of the unusual antibiograms of IMI-producing isolates.
Assuntos
Antibacterianos/farmacologia , Colistina/farmacologia , Enterobacter/efeitos dos fármacos , Enterobacter/isolamento & purificação , Adulto , Antibacterianos/uso terapêutico , Colistina/uso terapêutico , Farmacorresistência Bacteriana Múltipla , Feminino , Fosfomicina/farmacologia , Fosfomicina/uso terapêutico , Humanos , Irlanda , Masculino , Testes de Sensibilidade MicrobianaRESUMO
BACKGROUND: There is a disproportionately high number of cases of work-related asthma occurring in health care occupations due to agents such as glutaraldehyde, latex and cleaning products. AIMS: To understand the causes and measure trends over time of occupational asthma (OA) in health care workers (HCWs). METHODS: We reviewed OA notifications from the Midland Thoracic Society's Surveillance Scheme of Occupational Asthma (SHIELD) database in the West Midlands, UK, from 1991 to 2011 and gathered data on occupation, causative agent and annual number of notifications. RESULTS: There were 182 cases of OA in HCWs (median annual notifications = 7; interquartile range [IQR] = 5-11), representing 5-19% of annual SHIELD notifications. The modal annual notification was 20 (in 1996); notifications have declined since then, in line with total SHIELD notifications. The majority of cases (136; 75%) occurred in nursing, operating theatre, endoscopy and radiology staff. The most frequently implicated agents were glutaraldehyde (n = 69), latex (n = 47) and cleaning products (n = 27), accounting for 79% of the 182 cases. Cleaning product-related OA was an emerging cause with 22 cases after 2001 and only 5 cases between 1991 and 2000. CONCLUSIONS: Control measures within the UK National Health Service have seen a decline in OA in HCWs due to latex and glutaraldehyde, though OA remains a problem amongst HCWs exposed to cleaning products. Continuing efforts are required to limit the number of cases in this employment sector.
Assuntos
Poluentes Ocupacionais do Ar/efeitos adversos , Asma Ocupacional/prevenção & controle , Pessoal de Saúde , Exposição Ocupacional/efeitos adversos , Asma Ocupacional/epidemiologia , Asma Ocupacional/etiologia , Detergentes/efeitos adversos , Desinfetantes/efeitos adversos , Glutaral/efeitos adversos , Pessoal de Saúde/tendências , Humanos , Látex/efeitos adversos , Reino Unido/epidemiologiaRESUMO
More than 145 European hematopoietic SCT programs have received JACIE (Joint Accreditation Committee for ISCT Europe and EBMT) accreditation since 2000, demonstrating compliance with FACT (Foundation for the Accreditation of Cell Therapy)-JACIE international standards. The association of JACIE with improved patient outcome was recently documented. However, conditions in which quality management systems were introduced and the actual benefits remain to be fully evaluated. Our study focuses on one aspect of quality management: introduction and use of indicators. Through a questionnaire sent to JACIE-accredited centers and responses from 32 programs (or 40%), we identified 293 indicators, including 224 (76%) that were introduced during the preparatory phase of JACIE accreditation. Indicators were associated with the following processes: measurement, analysis and improvement (54/293 or 18%); donor collection (49/293 or 16%); processing and storage of cell therapy products (37/293 or 12.5%); and administration of hematopoietic progenitor cells (67/293 or 23%). Mapping revealed an uneven distribution of indicators across the different subprocesses that contribute to this highly specialized medical procedure. Moreover, we found that only 101/293 indicators (34%) complied with the rules for implementation of a quality indicator, as defined by the FDX 50-171 standard. This suggests that risks to donors/recipients are unevenly monitored, leaving critical medical steps with low levels of monitoring.