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1.
Cell ; 187(11): 2838-2854.e17, 2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-38744282

RESUMEN

Retrospective lineage reconstruction of humans predicts that dramatic clonal imbalances in the body can be traced to the 2-cell stage embryo. However, whether and how such clonal asymmetries arise in the embryo is unclear. Here, we performed prospective lineage tracing of human embryos using live imaging, non-invasive cell labeling, and computational predictions to determine the contribution of each 2-cell stage blastomere to the epiblast (body), hypoblast (yolk sac), and trophectoderm (placenta). We show that the majority of epiblast cells originate from only one blastomere of the 2-cell stage embryo. We observe that only one to three cells become internalized at the 8-to-16-cell stage transition. Moreover, these internalized cells are more frequently derived from the first cell to divide at the 2-cell stage. We propose that cell division dynamics and a cell internalization bottleneck in the early embryo establish asymmetry in the clonal composition of the future human body.


Asunto(s)
Blastómeros , Linaje de la Célula , Embrión de Mamíferos , Femenino , Humanos , Blastómeros/citología , Blastómeros/metabolismo , División Celular , Embrión de Mamíferos/citología , Embrión de Mamíferos/metabolismo , Desarrollo Embrionario , Estratos Germinativos/citología , Estratos Germinativos/metabolismo , Masculino , Animales , Ratones
2.
Clin Infect Dis ; 79(2): 555-561, 2024 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-38630638

RESUMEN

BACKGROUND: Outbreaks of vaccine-preventable diseases (VPDs) in healthcare workers (HCWs) can result in morbidity and mortality and cause significant disruptions to healthcare services, patients, and visitors as well as an added burden on the healthcare system. This scoping review aimed to describe the epidemiology of VPD outbreaks in HCWs caused by diseases that are prevented by the 10 vaccines recommended by the World Health Organization for HCWs. METHODS: In April 2022, CINAHL, MEDLINE, Global Health, and EMBASE were searched for all articles reporting on VPD outbreaks in HCWs since the year 2000. Articles were included regardless of language and study type. Clinical and epidemiological characteristics of VPD outbreaks were described. RESULTS: Our search found 9363 articles, of which 216 met the inclusion criteria. Studies describing 6 of the 10 VPDs were found: influenza, measles, varicella, tuberculosis, pertussis, and rubella. Most articles (93%) were from high- and upper-middle-income countries. While most outbreaks occurred in hospitals, several influenza outbreaks were reported in long-term-care facilities. Based on available data, vaccination rates among HCWs were rarely reported. CONCLUSIONS: We describe several VPD outbreaks in HCWs from 2000 to April 2022. The review emphasizes the need to understand the factors influencing outbreaks in HCWs and highlights the importance of vaccination among HCWs.


Asunto(s)
Brotes de Enfermedades , Personal de Salud , Vacunación , Enfermedades Prevenibles por Vacunación , Humanos , Personal de Salud/estadística & datos numéricos , Brotes de Enfermedades/prevención & control , Enfermedades Prevenibles por Vacunación/epidemiología , Enfermedades Prevenibles por Vacunación/prevención & control , Vacunación/estadística & datos numéricos , Gripe Humana/epidemiología , Gripe Humana/prevención & control
3.
Clin Immunol ; 260: 109914, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38286173

RESUMEN

OBJECTIVE: To investigate CD36 in ANCA-associated vasculitis (AAV), a condition characterized by monocyte/macrophage activation and vascular damage. METHODS: CD36 expression was assessed in AAV patients and healthy controls (HC). The impact of palmitic acid (PA) stimulation on multinucleate giant cell (MNGC) formation, macrophage, and endothelial cell activation, with or without CD36 knockdown, was examined. RESULTS: CD36 was overexpressed on AAV patients' monocytes compared to HC, regardless of disease activity. AAV patients exhibited elevated soluble CD36 levels in serum and plasma and PR3-ANCA patients' monocytes demonstrated increased MNGC formation following PA stimulation compared to HC. PA stimulation of macrophages or endothelial cells resulted in heightened CD36 expression, cell activation, increased macrophage migration inhibitory factor (MIF) production, and c-Myc expression, with attenuation upon CD36 knockdown. CONCLUSION: CD36 participates in macrophage and endothelial cell activation and MNGC formation, features of AAV pathogenesis. AAV treatment may involve targeting CD36 or MIF.


Asunto(s)
Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos , Anticuerpos Anticitoplasma de Neutrófilos , Humanos , Anticuerpos Anticitoplasma de Neutrófilos/metabolismo , Células Endoteliales/patología , Macrófagos/patología , Células Gigantes , Citoplasma/patología
4.
Zoo Biol ; 2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38874018

RESUMEN

Asian hornbills have limited ex situ breeding success, yet these species are some of the most threatened of birds, in need of managed breeding programs. To optimize breeding and increase the sustainability of such populations, it is necessary to assess and improve their husbandry and welfare. Evidence to improve reproduction can be gathered through global husbandry surveys. A survey was sent out to all European Association of Zoos and Aquaria and Association of Zoos and Aquarium holders of the wreathed hornbill (Rhyticeros undulatus) and Papuan hornbill (R. plicatus) to determine predictors for ex situ breeding success. This research found that pairs that have spent more years together (p = .016) and that adding additional proteins to the diet (p = .006) are two significant predictors of breeding success for wreathed- and Papuan hornbill pairs. This paper found a general trend that successful hornbill pairs prefer nest boxes that are situated outside (p = .054). The behaviors of calling to each other and sitting in close proximity showed a general trend and were observed more frequently in successful pairs and, therefore, could be good indicators of bonded pairs. We recommend that ex situ institutions allow their hornbill pairs time to form strong bonds, and that pair compatibility is monitored regularly to ensure that such interactions are positive and not consistently negative. An increase in the percentage of dietary proteins, prior and during the breeding season appears to stimulate pairs to breed. If the management and husbandry alterations presented in this study are implemented, the sustainability of Rhyticeros hornbill populations may be enhanced.

5.
Infect Immun ; 91(12): e0031123, 2023 Dec 12.
Artículo en Inglés | MEDLINE | ID: mdl-37909750

RESUMEN

Pulmonary host defense is critical for the control of lung infection and inflammation. An increased expression and activity of Toll-like receptor 4 (TLR4) induce phagocytic uptake/clearance and inflammation against Gram-negative bacteria. In this study, we addressed the mechanistic aspect of the immunomodulatory activity of the TLR4-interacting SPA4 peptide (amino acid sequence GDFRYSDGTPVNYTNWYRGE) against Escherichia coli. Binding of the SPA4 peptide to bacteria and direct anti-bacterial effects were investigated using flow cytometric, microscopic, and bacteriological methods. The bacterial uptake and inflammatory cytokine response were studied in dendritic cells expressing endogenous basal level of TLR4 or overexpressing TLR4. The subcellular distribution and co-localization of TLR4 and bacteria were investigated by immunocytochemistry. Furthermore, we studied the cellular expression and co-localization of endoplasmic reticulum (ER) molecules (calnexin and ER membrane protein complex subunit 1; EMC1) with lysosomal-associated membrane protein 1 (LAMP1) in cells infected with E. coli and treated with the SPA4 peptide. Simultaneously, the expression of histone H2A protein was quantitated by immunoblotting. Our results demonstrate no binding or direct killing of the bacteria by SPA4 peptide. Instead, it induces the uptake and localization of E. coli in the phagolysosomes for lysis and simultaneously suppresses the secreted levels of TNF-α. Overexpression of TLR4 further augments the pro-phagocytic and anti-inflammatory activity of SPA4 peptide. A time-dependent change in subcellular distribution of TLR4 and an increased co-localization of TLR4 with E. coli in SPA4 peptide-treated cells suggest an enhanced recognition and internalization of bacteria in conjugation with TLR4. Furthermore, an increased co-localization of calnexin and EMC1 with LAMP1 indicates the involvement of ER in pro-phagocytic activity of SPA4 peptide. Simultaneous reduction in secreted amounts of TNF-α coincides with suppressed histone H2A protein expression in the SPA4 peptide-treated cells. These results provide initial insights into the plausible role of ER and histones in the TLR4-immunomodulatory activity of SPA4 peptide against Gram-negative bacteria.


Asunto(s)
Escherichia coli , Receptor Toll-Like 4 , Humanos , Receptor Toll-Like 4/metabolismo , Escherichia coli/metabolismo , Histonas , Factor de Necrosis Tumoral alfa/metabolismo , Calnexina/metabolismo , Inflamación/metabolismo , Retículo Endoplásmico/metabolismo , Lipopolisacáridos/farmacología
6.
Rheumatology (Oxford) ; 62(2): 583-595, 2023 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-35731132

RESUMEN

OBJECTIVES: Sex is well known to influence risk, severity and treatment outcomes of RA, although the underlying causes are uncertain. The aim of this research was to examine whether factors influencing female sex hormones (reproductive status and exogenous sex hormone use) are associated with the efficacy of DMARDs. METHODS: Individual participant data were pooled from five phase 3 clinical trials where RA patients were treated with tocilizumab and/or conventional synthetic DMARDs. The primary outcome was the time to first remission according to the Simplified Disease Activity Index. The relationship between menopausal status or use of exogenous sex hormones and the time of first remission was assessed via Cox proportional analysis. Analysed data included sex, baseline menopausal status (premenopausal, perimenopausal, early postmenopausal and postmenopausal), participant age, body mass index, race, number of previous DMARDs and baseline disease activity. RESULTS: Analysis included 4474 female patients, of whom 2817 (62.9%) were postmenopausal, 202 (4.5%) were early postmenopausal, 1021 (22.8%) were premenopausal and 414 (9.2%) were perimenopausal. Of these, 221 (7.8%), 13 (6.4%), 255 (25%) and 47 (11.4%), respectively, were taking exogenous sex hormones. In the pooled analysis, perimenopausal status was associated with reduced remission compared with premenopausal status [adjusted HR 0.78 (95% CI 0.61, 0.99)]. Sex hormone use was associated with significantly higher remission [adjusted HR 1.20 (95% CI 1.01, 1.43)]. CONCLUSION: Perimenopausal women were less likely to achieve remission compared with premenopausal RA patients. The use of exogenous sex hormones appeared to be associated with more frequent remission in female RA patients, particularly those who were perimenopausal and early postmenopausal, although further research is required to confirm and identify the drivers for this observation and how it interacts with menopausal status.


Asunto(s)
Antirreumáticos , Artritis Reumatoide , Hormonas Esteroides Gonadales , Femenino , Humanos , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Antirreumáticos/efectos adversos , Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Hormonas Esteroides Gonadales/efectos adversos , Posmenopausia/efectos de los fármacos , Perimenopausia/efectos de los fármacos
7.
Med J Aust ; 218(11): 528-541, 2023 06 19.
Artículo en Inglés | MEDLINE | ID: mdl-37248802

RESUMEN

Vaccination in pregnancy is the best strategy to reduce complications from influenza or pertussis infection in infants who are too young to be protected directly from vaccination. Pregnant women are also at risk of influenza complications preventable through antenatal vaccination. Both vaccines are funded under the National Immunisation Program for pregnant women in Australia, but coverage is not routinely reported nationally. We reviewed all reported Australian maternal influenza and pertussis vaccine coverage data for the period 2016-2021, to identify gaps and information needs. Maternal influenza vaccine coverage was suboptimal at < 58% for 2016-2018, with higher coverage of 62-75% reported in two states (Victoria and Western Australia) for 2019-2021. Maternal pertussis vaccine coverage from 2016 was generally higher than for influenza at > 70%, with the highest jurisdictional coverage of 89% reported in Western Australia in 2020. Vaccination rates were often suboptimal among First Nations pregnant women and up to 20% lower than among non-First Nations Australian women; while data were limited, coverage was low among culturally and linguistically diverse women and among women of lower socio-economic status. Jurisdictional perinatal data collections were the best source of information on antenatal vaccine coverage but were only available for a minority of the population; a nationally consistent systematic approach is lacking. Timely and comprehensive data are needed to provide feedback to improve maternal vaccination coverage, particularly among groups with higher risk and/or low uptake, and as new vaccines are recommended, including COVID-19 vaccination.


Asunto(s)
COVID-19 , Vacunas contra la Influenza , Gripe Humana , Complicaciones Infecciosas del Embarazo , Tos Ferina , Lactante , Femenino , Embarazo , Humanos , Vacunas contra la Influenza/uso terapéutico , Vacuna contra la Tos Ferina , Gripe Humana/epidemiología , Gripe Humana/prevención & control , Vacunas contra la COVID-19 , Mujeres Embarazadas , Vacunación , Tos Ferina/epidemiología , Tos Ferina/prevención & control , Complicaciones Infecciosas del Embarazo/epidemiología , Complicaciones Infecciosas del Embarazo/prevención & control , Encuestas y Cuestionarios , Victoria
8.
J Paediatr Child Health ; 59(4): 686-693, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36807943

RESUMEN

AIM: Uptake of COVID-19 vaccines for children aged 5-11 years old in Australia has plateaued. Persuasive messaging is an efficient and adaptable potential intervention to promote vaccine uptake, but evidence for its effectiveness is varied and dependent on context and cultural values. This study aimed to test persuasive messages to promote COVID-19 vaccines for children in Australia. METHODS: A parallel, online, randomised control experiment was conducted between 14 and 21 January 2022. Participants were Australian parents of a child aged 5-11 years who had not vaccinated their child with a COVID-19 vaccine. After providing demographic details and level of vaccine hesitancy, parents viewed either the control message or one of four intervention texts emphasising (i) personal health benefits; (ii) community health benefits; (iii) non-health benefits; or (iv) personal agency. The primary outcome was parents' intention to vaccinate their child. RESULTS: The analysis included 463 participants, of whom 58.7% (272/463) were hesitant about COVID-19 vaccines for children. Intention to vaccinate was higher in the community health (7.8%, 95% confidence interval (CI) -5.3% to 21.0%) and non-health (6.9%, 95% CI -6.4% to 20.3%) groups, and lower in the personal agency group (-3.9, 95% CI -17.7 to 9.9) compared to control, but these differences did not reach statistical significance. The effects of the messages among hesitant parents were similar to the overall study population. CONCLUSION: Short, text-based messages alone are unlikely to influence parental intention to vaccinate their child with the COVID-19 vaccine. Multiple strategies tailored for the target audience should also be utilised.


Asunto(s)
COVID-19 , Vacunas , Niño , Preescolar , Humanos , Australia , COVID-19/prevención & control , Vacunas contra la COVID-19 , Conocimientos, Actitudes y Práctica en Salud , Intención , Padres , Vacunación
9.
Ecotoxicol Environ Saf ; 249: 114345, 2023 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-36508834

RESUMEN

Fuel spills are a major source of contamination in terrestrial environments in Antarctica. Little is known of the effects of hydrocarbon contaminants in fuels on Antarctic terrestrial biota, and how these change as fuel ages within soil. In this study we investigate the sensitivity of juveniles of the endemic Antarctic nematode Plectus murrayi to diesel-spiked soil. Toxicity tests were conducted on soil elutriates, and changes in concentrations of hydrocarbons, polar compounds and PAHs were assessed as the spiked soil was artificially aged at 3 °C over a 45-week period, representing multiple summer seasons of fuel degradation. Nematodes were most sensitive to elutriates made from freshly spiked soils (LC50 419 µg/L TPH and 156 µg/L TPH-SG), with a subsequent decline in toxicity observed in the first 6 weeks of laboratory ageing (LC50 2945 µg/L TPH and 694 µg/L TPH-SG). Effects were still evident up to 45 weeks (lowest observed effect concentration 2123 µg/L TPH) despite hydrocarbons being depleted from soils with ageing (84 % loss) and elutriates becoming dominated by polar metabolites (95 % polar). Nematode sensitivity throughout the ageing period showed evidence of a relationship between LC50 and the proportions of the lighter carbon range fraction of TPH in elutriates, the F2 fraction (C10-14). This study is the first to estimate the sensitivity of Antarctic terrestrial fauna to diesel and provides novel data on the dynamics of fuel chemistry under Antarctic conditions and how this influences toxicity. Findings contribute to predicting ecological risk at existing diesel fuel spill sites in Antarctica, to the derivation of site-specific remediation targets, and to environmental guidelines to assess ecosystem health.


Asunto(s)
Nematodos , Contaminantes del Suelo , Animales , Regiones Antárticas , Ecosistema , Suelo/química , Hidrocarburos/toxicidad , Contaminantes del Suelo/toxicidad , Contaminantes del Suelo/química
10.
J Clin Psychol ; 79(4): 1192-1207, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36459614

RESUMEN

OBJECTIVE: Previous research has documented associations between trauma and interpersonal problems. We examined the impact of trauma on interpersonal problems among depressed patients seeking treatment in a community mental health setting. METHODS: A total of 453 patients seeking treatment and screened for a comparative effectiveness study of therapies for depression were included. We conducted analyses relating the 32-item inventory of interpersonal problems (IIP-32) to trauma measures. RESULTS: 99.1% of the sample experienced a traumatic event. There were significant associations between the total number of traumas, the number of sexually and physically assaultive traumas, and both gender and race. The number of sexually assaultive traumas was significantly related to the IIP-32 "too caring" subscale (simple r = 0.167, p < 0.001). Controlling for demographics and other IIP-32 subscales, the total number of traumas remained significantly related to the IIP-32 "too caring" domain (partial r = 0.163, p < 0.001). CONCLUSIONS: Traumatic events are prevalent among community populations and these experiences are associated with certain interpersonal problems. Trauma and interpersonal problems are key issues for the treatment of patients in the community mental health setting.


Asunto(s)
Relaciones Interpersonales , Salud Mental , Humanos , Estados Unidos
11.
Zoo Biol ; 42(3): 343-356, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36642934

RESUMEN

As global wildlife populations continue to decline, the health and sustainability of ex situ populations in zoos and aquariums have become increasingly important. However, the majority of managed ex situ populations are not meeting sustainability criteria and are not viable in the long term. Historically, ex situ flamingo (Phoenicopteriformes) populations have shown low rates of reproductive success and improvements are needed for long-term viability. Both flock size and environmental suitability have previously been shown to be important determinants of ex situ flamingo reproductive success in a limited number of sites in some species. Here we combined current and historic globally shared zoological records for four of the six extant species of flamingo (Phoeniconaias minor, Phoenicopterus chilensis, Phoenicopterus roseus, and Phoenicopterus ruber) to analyze how flock size, structure, and climatic variables have influenced reproductive success in ex situ flamingo populations at 540 zoological institutions from 1990 to 2019. Flock size had a strong nonlinear relationship with reproductive success for all species, with flock sizes of 41-100 birds necessary to achieve ca. 50% probability of reproduction. Additionally, an even sex ratio and the introduction of new individuals to a flock both increased ex situ reproductive success in some cases, while climatic variables played a limited role. We demonstrate the conservation management potential from globally shared zoological data and provide species-specific management recommendations to increase the reproductive success of global ex situ flamingo populations: minimum flock sizes should be increased, and we encourage greater collaboration between individual institutions and regional associations in exchanging birds between flocks.


Asunto(s)
Animales Salvajes , Animales de Zoológico , Animales , Aves , Reproducción
12.
J Clin Immunol ; 41(1): 194-204, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33403466

RESUMEN

Influenza is a potential cause of severe disease in the immunocompromised. Patients with hypogammaglobulinemia, in spite of adequate replacement therapy, are at risk of significant morbidity and adverse outcomes. A seasonal vaccine is the primary prophylactic countermeasure to limit disease. The aim of this study was to evaluate the attitude, knowledge, and influenza vaccine uptake among Irish patients receiving immunoglobulin replacement therapy (IgRT), as well as uptake in co-habitants. Fifty-seven percent of patients receiving IgRT at a regional immunology referral center completed a questionnaire evaluation. Seventy-six percent of IgRT patients received the influenza vaccine for the 2019 season. Ninety-eight percent recognized that influenza could be prevented with vaccination, and 81% deemed it a safe treatment. Ninety-three percent correctly identified that having a chronic medical condition, independent of age, was an indication for vaccination. Despite excellent compliance and knowledge, many were not aware that vaccination was recommended for co-habitants, and only 24% had full vaccine coverage at home. Those who received advice regarding vaccination of household members had higher rates of uptake at home. This study demonstrates awareness and adherence to seasonal influenza vaccine recommendations among patients receiving IgRT. Over three quarters felt adequately informed, the majority stating physicians as their information source. We identified an easily modifiable knowledge gap regarding vaccination of household members. This data reveals a need to emphasize the importance of vaccination for close contacts of at-risk patients, to maintain optimal immunity and health outcome.


Asunto(s)
Conocimientos, Actitudes y Práctica en Salud , Vacunas contra la Influenza/inmunología , Gripe Humana/epidemiología , Gripe Humana/prevención & control , Adulto , Agammaglobulinemia/complicaciones , Agammaglobulinemia/tratamiento farmacológico , Agammaglobulinemia/epidemiología , Agammaglobulinemia/etiología , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Inmunoglobulinas Intravenosas/administración & dosificación , Vacunas contra la Influenza/administración & dosificación , Gripe Humana/complicaciones , Masculino , Persona de Mediana Edad , Vigilancia en Salud Pública , Vacunación , Adulto Joven
13.
J Pediatr ; 239: 39-49.e9, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34181989

RESUMEN

OBJECTIVES: To describe the features and frequency of respiratory syncytial virus (RSV)-associated severe acute neurologic disease in children. STUDY DESIGN: We performed a systematic review of the literature to identify reports of severe acute neurologic complications associated with acute RSV infection in children aged <15 years (PROSPERO Registration CRD42019125722). Main outcomes included neurologic, clinical, and demographic features of cases and the frequency of disease. We aggregated available case data from the published literature and from the Australian Acute Childhood Encephalitis (ACE) study. RESULTS: We identified 87 unique studies from 26 countries describing a spectrum of RSV-associated severe acute neurologic syndromes including proven encephalitis, acute encephalopathy, complex seizures, hyponatremic seizures, and immune-mediated disorders. The frequency of RSV infection in acute childhood encephalitis/encephalopathy was 1.2%-6.5%. We aggregated data from 155 individual cases with RSV-associated severe acute neurologic complications; median age was 11.0 months (IQR 2.0-21.5), most were previously healthy (71/104, 68%). Seizure was the most frequently reported neurologic feature (127/150, 85%). RSV was detected in the central nervous system of 12 cases. Most children recovered (81/122, 66%); however, some reports described partial recovery (33/122, 27%) and death (8/122, 7%). CONCLUSIONS: RSV-associated neurologic complications have been widely reported, but there is substantial heterogeneity in the design and quality of existing studies. The findings from our study have implications for the investigation, management, and prevention of RSV-associated neurologic complications. Further, this systematic review can inform the design of future studies aiming to quantify the burden of childhood RSV-associated neurologic disease.


Asunto(s)
Enfermedades del Sistema Nervioso/epidemiología , Infecciones por Virus Sincitial Respiratorio/epidemiología , Adolescente , Niño , Preescolar , Pruebas Diagnósticas de Rutina/estadística & datos numéricos , Femenino , Humanos , Incidencia , Lactante , Masculino , Virus Sincitial Respiratorio Humano/aislamiento & purificación
14.
Mol Psychiatry ; 25(7): 1469-1476, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-31427754

RESUMEN

Depression affects all aspects of an individual's life but evidence relating to the causal effects on health is limited. We used information from 337,536 UK Biobank participants and performed hypothesis-free phenome-wide association analyses between major depressive disorder (MDD) genetic risk score (GRS) and 925 disease outcomes. GRS-disease outcome associations passing the multiple-testing corrected significance threshold (P < 1.9 × 10-3) were followed by Mendelian randomisation (MR) analyses to test for causality. MDD GRS was associated with 22 distinct diseases in the phenome-wide discovery stage, with the strongest signal observed for MDD diagnosis and related co-morbidities including anxiety and sleep disorders. In inverse-variance weighted MR analyses, MDD was associated with several inflammatory and haemorrhagic gastrointestinal diseases, including oesophagitis (OR 1.32, 95% CI 1.18-1.48), non-infectious gastroenteritis (OR 1.25, 95% CI 1.06-1.48), gastrointestinal haemorrhage (OR 1.26, 95% CI 1.11-1.43) and intestinal E.coli infections (OR 3.24, 95% CI 1.74-6.02). Signals were also observed for symptoms/disorders of the urinary system (OR 1.36, 95% CI 1.19-1.56), asthma (OR 1.23, 95% CI 1.06-1.44), and painful respiration (OR 1.28, 95% CI 1.14-1.44). MDD was associated with disorders of lipid metabolism (OR 1.22, 95% CI 1.12-1.34) and ischaemic heart disease (OR 1.30, 95% CI 1.15-1.47). Sensitivity analyses excluding pleiotropic variants provided consistent associations. Our study indicates a causal link between MDD and a broad range of diseases, suggesting a notable burden of co-morbidity. Early detection and management of MDD is important, and treatment strategies should be selected to also minimise the risk of related co-morbidities.


Asunto(s)
Bases de Datos Factuales , Trastorno Depresivo Mayor/diagnóstico , Trastorno Depresivo Mayor/psicología , Análisis de la Aleatorización Mendeliana , Fenotipo , Adulto , Anciano , Trastorno Depresivo Mayor/genética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reino Unido
15.
Pharmacol Res ; 173: 105887, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34536550

RESUMEN

Rheumatoid arthritis (RA) is a common autoimmune inflammatory disease affecting 0.5-1% of adults worldwide. Achieving long term remission or low disease activity is possible through early diagnosis, rapid initiation of disease modifying anti-rheumatic drugs (DMARDs) and implementation of a treat to target approach. Initial DMARD therapy usually involves methotrexate (MTX), either alone or in combination with other agents, however 40% of RA patients do not respond adequately, putting them at risk of disease progression and unnecessary exposure to MTX related adverse effects. Early predictors of MTX response would therefore enable a more personalized treatment strategy, ensuring timely access to MTX for those likely to respond and importantly, early initiation of alternative treatment for those in which MTX is unlikely to be efficacious. Predicting response to treatment will most likely require consideration of the clinical characteristics of the patient and interrogation of a number of factors including genetic, epigenetic, cell free DNA (cfDNA) and microRNA (miRNA), all of which can be investigated through blood derived liquid biopsies. This review will summarize the existing literature examining the use of epigenetic factors, cfDNA and miRNA as response predictors among RA patients treated with MTX.


Asunto(s)
Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/genética , Metotrexato/uso terapéutico , Antirreumáticos/farmacología , Ácidos Nucleicos Libres de Células , Epigénesis Genética , Humanos , Biopsia Líquida , Metotrexato/farmacología , MicroARNs , Resultado del Tratamiento
16.
Pediatr Transplant ; 25(2): e13855, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33022813

RESUMEN

For patients with bone marrow failure syndromes (BMFS) who may tolerate gradual donor engraftment and achieve adequate disease control with stable mixed chimerism, RIC regimens may be preferable to myeloablative regimens. We performed a retrospective analysis of outcomes for patients who underwent HSCT at our institution between 2009 and 2017 for BMFS using an irradiation-free RIC regimen. Fourteen pediatric patients with BMFS received fludarabine (30 mg/m2 IV daily × 3), thiotepa (5 mg/kg IV every 12 hours × 2), and melphalan (70 mg/m2 IV daily × 2) prior to HSCT. Our cohort included the following diagnoses: SAA (n = 7), CAMT (n = 4), SCN (n = 1), DBA (n = 1), and non-Fanconi congenital BMF (n = 1). Seven patients underwent a MSD transplant; seven underwent an unrelated donor transplant. All patients are alive with median follow-up of 1112 days (range 455-2549 days). The median time to neutrophil engraftment was 16 days (range 10-26 days). All were transfusion independent by day + 100. The highest grade of aGVHD was grade 2; 8 (57%) did not develop aGVHD. Four (28.5%) developed extensive cGVHD, 4 (28.5%) developed limited cGVHD, and 6 (43%) did not develop cGVHD. No patients developed SOS. None died from GVHD or infectious complications. HSCT with RIC with fludarabine, thiotepa, and melphalan for BMFS was effective with a tolerable safety profile. Probability of OS at 100 days and 1 year was 100%.


Asunto(s)
Trastornos de Fallo de la Médula Ósea/terapia , Trasplante de Células Madre Hematopoyéticas , Agonistas Mieloablativos/uso terapéutico , Acondicionamiento Pretrasplante/métodos , Adolescente , Niño , Preescolar , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Enfermedad Injerto contra Huésped/prevención & control , Humanos , Lactante , Masculino , Estudios Retrospectivos , Resultado del Tratamiento , Adulto Joven
17.
Psychother Res ; 31(7): 909-920, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-33377425

RESUMEN

To examine the association between adherence and competence in cognitive therapy (CT) techniques and change in positive compensatory skills and depressive symptoms within a community mental health setting.Adherence ratings were available for 97 individuals receiving CT for major depressive disorder. Assessments of adherence and competence were rated on one early session of CT. Compensatory skills were measured using the Ways of Responding Community Version at baseline and months 1, 2, and 5. Symptom severity was evaluated using the Hamilton Rating Scale for Depression at baseline and months 1, 2, 4, and 5.In mixed effects models, adherence was significantly associated with linear change in positive compensatory skills from baseline to month 5 (F [1, 76] = 8.05, p=.006, r=.31). Competence was also significantly associated with change in positive compensatory skills from baseline to month 5 (F [1, 78] = 5.1, p=.027, r=.25). High adherence was associated with improvements in HAM-D scores from baseline to month 5 (F [1, 78] = 5.1, p=.027, r=.25).Results support the hypothesis that use of CT techniques is associated with change in compensatory skills in a community mental health setting.


Asunto(s)
Terapia Cognitivo-Conductual , Trastorno Depresivo Mayor , Terapia Psicoanalítica , Cognición , Trastorno Depresivo Mayor/terapia , Humanos , Salud Mental , Resultado del Tratamiento
18.
Environ Sci Technol ; 54(1): 306-315, 2020 01 07.
Artículo en Inglés | MEDLINE | ID: mdl-31657908

RESUMEN

Robust environmental assessments and contaminant monitoring in Antarctic near-shore marine environments need new techniques to overcome challenges presented by a highly dynamic environment. This study outlines an approach for contaminant monitoring and risk assessment in Antarctic marine conditions using diffusive gradients in thin-films (DGT) coupled to regionally specific ecotoxicology data and environmental quality standards. This is demonstrated in a field study where DGT samplers were deployed in the near-shore marine environment of East Antarctica around the operational Casey station and the abandoned Wilkes station to measure the time-averaged biologically available fraction of metal contaminants. The incorporation of DGT-labile concentrations to reference toxicity mixture models for three Antarctic organisms predicted low toxic effects (<5% effect to the growth or development of each organism). The comparison of metal concentrations to the Australian and New Zealand default water quality guideline values (WQGVs) showed no marine site exceeding the WQGVs for 95% species protection. However, all sites exceeded the 99% WQGVs due to copper concentrations that are likely of geogenic origin (i.e., not from anthropogenic sources). This study provides evidence supporting the use of the DGT technique to monitor contaminants and assess their environmental risk in the near-shore marine environment of Antarctica.


Asunto(s)
Monitoreo del Ambiente , Contaminantes Químicos del Agua , Regiones Antárticas , Australia , Metales , Nueva Zelanda
19.
BMC Public Health ; 20(1): 1253, 2020 Aug 17.
Artículo en Inglés | MEDLINE | ID: mdl-32807124

RESUMEN

BACKGROUND: Acceptance of vaccines is an important predictor of vaccine uptake. This has public health implications as those who are not vaccinated are at a higher risk of infection from vaccine preventable diseases. We aimed to examine how parental attitudes and beliefs towards childhood vaccination were measured in questionnaires through a systematic review of the literature. METHODS: We systematically reviewed the literature to identify primary research studies using tools to measure vaccine attitudes and beliefs, published between January 2012 and May 2018. Studies were included if they involved a quantitative survey of the attitudes and beliefs of parents about vaccinations recommended for children. We undertook a synthesis of the results with a focus on evaluating the tools used to measure hesitancy. RESULTS: A total of 116 studies met the inclusion criteria, 99 used a cross sectional study design, 5 used a case control study design, 4 used a pre-post study design and 8 used mixed methods study designs. Sample sizes of included studies ranged from 49 to 12,259. The most commonly used tool was the Parent Attitudes about Childhood Vaccines (PACV) Survey (n = 7). The most common theoretical framework used was the Health Belief Model (n = 25). Questions eliciting vaccination attitudes and beliefs varied widely. CONCLUSIONS: There was heterogeneity in the types of questionnaires used in studies investigating attitudes and beliefs about vaccination in parents. Methods to measure parental attitudes and beliefs about vaccination could be improved with validated and standardised yet flexible instruments. The use of a standard set of questions should be encouraged in this area of study.


Asunto(s)
Salud Infantil , Conocimientos, Actitudes y Práctica en Salud , Padres/psicología , Aceptación de la Atención de Salud , Vacunación/psicología , Estudios de Casos y Controles , Niño , Preescolar , Estudios Transversales , Cultura , Femenino , Humanos , Masculino , Encuestas y Cuestionarios
20.
J Med Internet Res ; 22(5): e16763, 2020 05 13.
Artículo en Inglés | MEDLINE | ID: mdl-32401220

RESUMEN

BACKGROUND: Internet search engines are increasingly being utilized as the first port of call for medical information by the public. The prevalence of allergies in developed countries has risen steadily over time. There exists significant variability in the quality of health-related information available on the web. Inaccurately diagnosed and mismanaged allergic disease has major downstream effects on patients, general practitioners, and regional allergy services. OBJECTIVE: This study aimed to verify whether Ireland has a relatively high rate of web-based allergy-related searches, to establish the proportion of medically accurate web pages encountered by the public, and to compare current search results localized to Dublin, Ireland with urban centers elsewhere. METHODS: Google Trends was used to evaluate regional interest of allergy-related search terms over a 10-year period using terms "allergy," "allergy test," "food allergy," and "food intolerance." These terms were then inputted into Google search, localizing them to cities in Ireland, the United Kingdom, and the United States. Output for each search was reviewed by two independent clinicians and deemed rational or nonevidence based, as per current best practice guidelines. Searches localized to Dublin were initially completed in 2015 and repeated in 2019 to assess for changes in the quality of search results over time. RESULTS: Ireland has a persistently high demand for web-based information relating to allergy and ranks first worldwide for "allergy test," second for "food allergy" and "food intolerance," and seventh for "allergy" over the specified 10-year timeframe. Results for each of the four subsearches in Dublin (2015) showed that over 60% of websites promoted nonevidence-based diagnostics. A marginal improvement in scientifically robust information was seen in 2019, but results for "allergy test" and "food intolerance" continued to promote alternative testing 57% (8/14) of the time. This strongly contrasted with results localized to Southampton and Rochester, where academic and hospital-affiliated web pages predominantly featured. Government-funded Department of Health websites did not feature in the top five results for Dublin searches "allergy testing," "food allergy," or "food intolerance" in either 2015 or 2019. CONCLUSIONS: The Irish public demonstrates a keen interest in seeking allergy-related information on the web. The proportion of evidence-based websites encountered by the Irish public is considerably lower than that encountered by patients in other urban centers. Factors contributing to this are the lack of a specialist register for allergy in Ireland, inadequate funding for allergy centers currently in operation, and insufficient promotion by the health service of their web-based health database, which contains useful patient-oriented information on allergy. Increased funding of clinical allergology services will more meaningfully impact the health of patients if there is a parallel investment by the health service in information and communication technology consultancy to amplify their presence on the web.


Asunto(s)
Hipersensibilidad/epidemiología , Internet/instrumentación , Motor de Búsqueda , Humanos , Irlanda/epidemiología
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