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1.
Artigo em Inglês | MEDLINE | ID: mdl-38977506

RESUMO

PURPOSE: In 2012, the UK government announced legislation changes and heightened immigration controls designed to create a 'hostile environment for illegal migration.' We measured changes in psychological distress among people from minoritised ethnic groups compared to White British controls before and throughout the implementation of these policies. METHODS: We used the UK Household Longitudinal Survey to estimate difference-in-difference models for six ethnic groups (Bangladeshi, African, Caribbean, Indian, Pakistani, and White British) in three eras: pre-policy (2009-2012); (2) transition (2012-2016); and (3) ongoing policy (2016-2020). We calculated the adjusted marginal mean psychological distress score at each era using the 12-item General Health Questionnaire (GHQ). RESULTS: In the pre-policy era, we found higher psychological distress for the Pakistani, Bangladeshi, and Caribbean groups compared to the White British group. We observed patterns consistent with increasing psychological distress during the transition era for the Pakistani and Bangladeshi groups, with further increases in the ongoing era for the Bangladeshi group. Levels of psychological distress the Indian and African groups were similar to the White British group in the pre-policy era and decreased over successive eras. A small decrease was observed in the Caribbean group across policy eras, while levels remained stable in the White British group. CONCLUSION: We found evidence that psychological distress increased among Pakistani and Bangladeshi individuals following the introduction of hostile environment policies but did not detect increased distress in other ethnic groups. This finding underscores the importance of disaggregating analyses by ethnic group to capture the distinct experiences.

2.
J Dairy Sci ; 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38825133

RESUMO

The CellCheck Dry Cow Consult (DCC) was developed by the CellCheck Technical Working Group to enable farmers to engage with their nominated vet to develop farm-specific selective dry cow therapy (SDCT) plans, where appropriate. This study evaluated the effect of the DCC on farmer decision-making around dry cow therapy, and the udder health impact of implementing SDCT, in study herds over the 2019 and 2020 dry periods. The DCC was a 3-h consult, delivered and funded as part of the Targeted Advisory Service on Animal Health (TASAH). Herds that completed a DCC were invited to register for a Dry Cow Review the following year. The combined data set for analysis across both years comprised of 439 herds and 25,357 cows. Available herd size ranged from 25 to 800. The median SCC of cows dried off with teat sealant only was 47,000 cells/ml before drying off in 2019 and 48,000 cells/ml at first milk recording in 2020, and 43,000 cells/ml before drying off in 2020 and 39,000 cells/ml at first milking recording in 2021. Following both the 2019 and 2020 dry periods, cows tended to converge toward a similar median SCC early in the following lactation, irrespective of prior dry cow treatment strategy. The uptake of SDCT was greater in Review herds, with 21% of cows receiving teat sealant only in 2020, compared with 16.3% of cows in herds participating in a Consult for the first time in 2020. At an individual cow level, in both years dry period new infection rate (NIR) was approximately 2.7% higher for cows treated with teat sealant only, than for those treated with both dry cow antibiotic tubes and teat sealant, and 1.2% higher than cows treated with antibiotic only. Regardless of treatment, there was a significant association between increasing parity and the risk of a dry period new infection. Increasing herd size had a statistically significant effect on the risk of dry period new infection rates. At a herd level, there was no statistically significant increase in NIR when SDCT was used compared with herds where blanket dry cow therapy was used. While not without risk, SDCT can be successfully implemented in Irish herds; however, constant attention to hygiene and management is essential. Though there are challenges to face, facilitating continued farmer education and engagement with professional guidance will be important.

3.
Psychol Med ; 53(6): 2553-2562, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-35094717

RESUMO

BACKGROUND: Racial and ethnic groups in the USA differ in the prevalence of posttraumatic stress disorder (PTSD). Recent research however has not observed consistent racial/ethnic differences in posttraumatic stress in the early aftermath of trauma, suggesting that such differences in chronic PTSD rates may be related to differences in recovery over time. METHODS: As part of the multisite, longitudinal AURORA study, we investigated racial/ethnic differences in PTSD and related outcomes within 3 months after trauma. Participants (n = 930) were recruited from emergency departments across the USA and provided periodic (2 weeks, 8 weeks, and 3 months after trauma) self-report assessments of PTSD, depression, dissociation, anxiety, and resilience. Linear models were completed to investigate racial/ethnic differences in posttraumatic dysfunction with subsequent follow-up models assessing potential effects of prior life stressors. RESULTS: Racial/ethnic groups did not differ in symptoms over time; however, Black participants showed reduced posttraumatic depression and anxiety symptoms overall compared to Hispanic participants and White participants. Racial/ethnic differences were not attenuated after accounting for differences in sociodemographic factors. However, racial/ethnic differences in depression and anxiety were no longer significant after accounting for greater prior trauma exposure and childhood emotional abuse in White participants. CONCLUSIONS: The present findings suggest prior differences in previous trauma exposure partially mediate the observed racial/ethnic differences in posttraumatic depression and anxiety symptoms following a recent trauma. Our findings further demonstrate that racial/ethnic groups show similar rates of symptom recovery over time. Future work utilizing longer time-scale data is needed to elucidate potential racial/ethnic differences in long-term symptom trajectories.


Assuntos
Depressão , Transtornos de Estresse Pós-Traumáticos , Humanos , Criança , Depressão/psicologia , Transtornos de Ansiedade , Ansiedade/epidemiologia , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Etnicidade/psicologia
4.
Soc Psychiatry Psychiatr Epidemiol ; 57(7): 1357-1364, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35150309

RESUMO

BACKGROUND: Schizophrenia has a significant and lasting impact on the quality of life of patients and their families and is a leading cause of disability globally. Family interventions can be beneficial and may be particularly appropriate in settings with limited resources. We conducted an exploratory trial testing the effectiveness of a multifamily group intervention, which draws on the traditions of psychoeducation and trialogue, for improving the quality of life of patients with schizophrenia in Bosnia and Herzegovina. METHODS: We conducted an exploratory, randomised controlled trial with patients with schizophrenia attending an outpatient clinic in Sarajevo. Our primary outcome was improved quality of life at 6-month follow-up. Secondary outcomes included objective social outcomes, psychiatric symptoms and psychiatric hospitalisation measured at 6 and 12 months. Experiences of participants were assessed in post-intervention interviews. RESULTS: 72 patients were randomly assigned to either one of six multifamily groups or treatment as usual. Follow-up assessments were completed with 53 patients (74%) at 6 months and 55 patients (76%) at 12 months. The intervention significantly improved quality of life at 6 months (Cohen's d = 0.78, F = 6.37, p = 0.016) and 12 months (d = 1.08, F = 17.92, p < 0.001), compared with treatment as usual. Re-hospitalisation rates at 6 months and symptom levels also improved significantly whilst changes in other secondary outcomes failed to reach statistical significance. CONCLUSION: These findings suggest multifamily groups can be effective for improving the quality of life of patients with schizophrenia in Bosnia and Herzegovina. Further research is required to assess how multifamily groups may be scaled up in similar settings with limited resources.


Assuntos
Esquizofrenia , Bósnia e Herzegóvina , Hospitalização , Humanos , Qualidade de Vida , Esquizofrenia/terapia
5.
Cancer Immunol Immunother ; 70(3): 743-753, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32918586

RESUMO

BACKGROUND: We conducted a phase 1 dose escalation study (ACTRN12618000140257 registered on 30/01/2018) to evaluate the safety, tolerability and immunogenicity of a therapeutic human papillomavirus (HPV) DNA vaccine (AMV002) in subjects previously treated for HPV-associated oropharyngeal squamous cell carcinoma (OPSCC). METHODS: Eligible subjects had to have no evidence of recurrent and/or metastatic disease at least 12 weeks following the completion of treatment. Three dosing cohorts each consisted of four subjects: group 1: 0.25 mg/dose, group 2: 1 mg/dose, group 3: 4 mg/dose. AMV002 was delivered intradermally on days 0, 28 and 56. Incidence and severity of treatment-emergent adverse events (TEAE) including local reaction at the injection site, and vaccination compliance were recorded. T cell and antibody responses to HPV16 E6 and E7 were measured by interferon gamma (IFN-γ) enzyme-linked immunosorbent spot (ELISpot) assay and enzyme-linked immunosorbent assay (ELISA). RESULTS: All subjects completed the vaccination programme and experienced mild discomfort at the injection site(s). Pre-immunisation, cell-mediated responses to HPV16 E6 and E7 were evident in all subjects, and E7-specific antibodies were detected in 11 (91.7%), reflecting previous exposure to HPV. Post-vaccination, 10 of 12 (83.3%) subjects responded to one or more of the E6 and/or E7 peptide pools, while 2 (16.7%) did not show additional vaccine-induced cell-mediated responses. Vaccination resulted in a ≥ 4-fold increase in anti-HPV16 E7 antibody titre in one subject in group 3. CONCLUSIONS: AMV002 was well tolerated at all dose levels and resulted in enhanced specific immunity to virus-derived tumour-associated antigens in subjects previously treated for HPV-associated OPSCC.


Assuntos
Alphapapillomavirus/imunologia , Neoplasias de Cabeça e Pescoço/etiologia , Neoplasias de Cabeça e Pescoço/prevenção & controle , Imunogenicidade da Vacina , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/imunologia , Vacinas contra Papillomavirus/imunologia , Anticorpos Antivirais/imunologia , Feminino , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/mortalidade , Humanos , Imunidade Celular/imunologia , Imunoglobulina G/imunologia , Masculino , Infecções por Papillomavirus/prevenção & controle , Infecções por Papillomavirus/virologia , Vacinas contra Papillomavirus/administração & dosagem , Vacinas contra Papillomavirus/efeitos adversos , Resultado do Tratamento , Vacinas de DNA/imunologia
6.
BMC Public Health ; 21(1): 1691, 2021 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-34530779

RESUMO

BACKGROUND: Public mental health (PMH) aims to improve wellbeing and prevent poor mental health at the population level. It is a global challenge and a UK priority area for action. Communities play an important role in the provision of PMH interventions. However, the evidence base concerning community-based PMH interventions is limited, meaning it is challenging to compare service provision to need. Without this, the efficient and equitable provision of services is hindered. Here, we sought to map the current range of community-based interventions for improving mental health and wellbeing currently provided in England to inform priority areas for policy and service intervention. METHOD: We adopted an established mapping exercise methodology, comparing service provision with demographic and deprivation statistics. Five local authority areas of England were selected based on differing demographics, mental health needs and wider challenging circumstances (i.e. high deprivation). Community-based interventions were identified through: 1) desk-based research 2) established professional networks 3) chain-referral sampling of individuals involved in local mental health promotion and prevention and 4) peer researchers' insight. We included all community-based, non-clinical interventions aimed at adult residents operating between July 2019 and May 2020. RESULTS: 407 interventions were identified across the five areas addressing 16 risk/protective factors for PMH. Interventions for social isolation and loneliness were most prevalent, most commonly through social activities and/or befriending services. The most common subpopulations targeted were older adults and people from minority ethnic backgrounds. Interventions focusing on broader structural and environmental determinants were uncommon. There was some evidence of service provision being tailored to local need, though this was inconsistent, meaning some at-risk groups such as men or LGBTQ+ people from minority ethnic backgrounds were missed. Interventions were not consistently evaluated. CONCLUSIONS: There was evidence of partial responsiveness to national and local prioritising. Provision was geared mainly towards addressing social and individual determinants of PMH, suggesting more integration is needed to engage wider service providers and policy-makers in PMH strategy and delivery at the community level. The lack of comprehensive evaluation of services to improve PMH needs to be urgently addressed to determine the extent of their effectiveness in communities they serve.


Assuntos
Promoção da Saúde , Saúde Mental , Idoso , Inglaterra , Exercício Físico , Humanos , Masculino , Políticas
7.
Plant Dis ; 104(3): 951-957, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31891549

RESUMO

This research was conducted to identify species causing powdery mildew on cucurbits and to determine genetic variations among isolates of the pathogen. We collected 109 isolates from six cucurbit species hosts (Cucumis melo, Cucumis sativus, Cucurbita maxima, Cucurbita moschata, Cucurbita pepo, and Lagenaria siceraria) in California, Illinois, Indiana, Michigan, New York, Texas, Washington, and Wisconsin in the United States and in Italy. By sequencing the internal transcribed spacer region of the nuclear rDNA of these 109 isolates, Podosphaera xanthii was found as the only species causing powdery mildew on cucurbits in the United States. Genotyping-by-sequencing was applied to these 109 isolates to investigate their genetic diversity, which showed a trend of isolates clustering from New York and Italy. In addition, the virulence of 36 isolates was compared and a significant difference (P < 0.0001) was found among them. Furthermore, results of the virulence tests of 28 isolates from Illinois showed significant effects of collection years, hosts, and locations on the virulence of the isolates.


Assuntos
Variação Genética , Doenças das Plantas , California , Genótipo , Illinois , Itália , Michigan , New York , Texas , Washington , Wisconsin
8.
Int J Biometeorol ; 62(4): 655-668, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29177798

RESUMO

Cucurbit downy mildew caused by the obligate oomycete, Pseudoperonospora cubensis, is considered one of the most economically important diseases of cucurbits worldwide. In the continental United States, the pathogen overwinters in southern Florida and along the coast of the Gulf of Mexico. Outbreaks of the disease in northern states occur annually via long-distance aerial transport of sporangia from infected source fields. An integrated aerobiological modeling system has been developed to predict the risk of disease occurrence and to facilitate timely use of fungicides for disease management. The forecasting system, which combines information on known inoculum sources, long-distance atmospheric spore transport and spore deposition modules, was tested to determine its accuracy in predicting risk of disease outbreak. Rainwater samples at disease monitoring sites in Alabama, Georgia, Louisiana, New York, North Carolina, Ohio, Pennsylvania and South Carolina were collected weekly from planting to the first appearance of symptoms at the field sites during the 2013, 2014, and 2015 growing seasons. A conventional PCR assay with primers specific to P. cubensis was used to detect the presence of sporangia in rain water samples. Disease forecasts were monitored and recorded for each site after each rain event until initial disease symptoms appeared. The pathogen was detected in 38 of the 187 rainwater samples collected during the study period. The forecasting system correctly predicted the risk of disease outbreak based on the presence of sporangia or appearance of initial disease symptoms with an overall accuracy rate of 66 and 75%, respectively. In addition, the probability that the forecasting system correctly classified the presence or absence of disease was ≥ 73%. The true skill statistic calculated based on the appearance of disease symptoms in cucurbit field plantings ranged from 0.42 to 0.58, indicating that the disease forecasting system had an acceptable to good performance in predicting the risk of cucurbit downy mildew outbreak in the eastern United States.


Assuntos
Modelos Teóricos , Micoses , Oomicetos , Doenças das Plantas , Chuva/microbiologia , Cucurbitaceae , Previsões , Risco , Estados Unidos
9.
Am J Transplant ; 17(9): 2326-2337, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28296000

RESUMO

Ischemia-reperfusion injury (IRI) evokes intragraft inflammatory responses, which markedly augment alloimmune responses against the graft. Understanding the mechanisms underlying these responses is fundamental to develop therapeutic regimens to prevent/ameliorate organ IRI. Here, we demonstrate that IRI results in a marked increase in mitochondrial damage and autophagy in dendritic cells (DCs). While autophagy is a survival mechanism for ischemic DCs, it also augments their production of interleukin (IL)-6. Allograft-derived dendritic cells (ADDCs) lacking autophagy-related gene 5 (Atg5) showed higher death rates posttransplantation. Transplanted ischemic hearts from CD11cCre/Atg5 conditional knockout mice showed marked reduction in intragraft expression of IL-6 compared with controls. To antagonize the effect of IL-6 locally in the heart, we synthesized novel anti-IL-6 nanoparticles with capacity for controlled release of anti-IL-6 over time. Compared with systemic delivery of anti-IL-6, localized delivery of anti-IL-6 significantly reduced chronic rejection with a markedly lower amount administered. Despite improved allograft histology, there were no changes to splenic T cell populations, illustrating the importance of local IL-6 in driving chronic rejection after IRI. These data carry potential clinical significance by identifying an innovative, targeted strategy to manipulate organs before transplantation to diminish inflammation, leading to improved long-term outcomes.


Assuntos
Anticorpos Monoclonais/farmacologia , Sistemas de Liberação de Medicamentos , Rejeição de Enxerto/prevenção & controle , Transplante de Coração/efeitos adversos , Interleucina-6/antagonistas & inibidores , Nanopartículas/administração & dosagem , Traumatismo por Reperfusão/prevenção & controle , Animais , Proteína 5 Relacionada à Autofagia/fisiologia , Células Cultivadas , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/imunologia , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/metabolismo , Sobrevivência de Enxerto/efeitos dos fármacos , Sobrevivência de Enxerto/imunologia , Inflamação/etiologia , Inflamação/metabolismo , Inflamação/prevenção & controle , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Nanopartículas/química , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/metabolismo
11.
Clin Anat ; 29(5): 547-54, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26457477

RESUMO

Charcot-Marie-Tooth 1A (CMT1A) is regarded as the most common hereditary peripheral neurodegenerative disorder. This narrative review highlights perspectives around the historically well-established and characteristic anatomical manifestations of CMT1A seen in the feet, legs and hands, in addition to a clinical diagnosis that may be confirmed by electrophysiology, genetic or molecular markers together with the presence of a typical family history. A less well-known perspective is the potential for systemic manifestations and wider complication. The condition is characterised by a progressive clinical picture with unmistakable anatomical and neurological features that have been described since the late 19th century. There remains no cure although supportive, rehabilitative, and surgical regimes may provide helpful management or amelioration of symptoms. Most recently, the emergence of a pleotherapeutic approach suggests distinct promise. Future research focused on a detailed elucidation of the underlying molecular mechanisms underpinning myelin and axonal function may eventually hold the key to successful treatment of CMT1A. Genetic modification would potentially present a cure. Clin. Anat. 29:547-554, 2016. © 2015 Wiley Periodicals, Inc.


Assuntos
Doença de Charcot-Marie-Tooth/patologia , Doença de Charcot-Marie-Tooth/terapia , Mãos/patologia , Extremidade Inferior/patologia , Humanos
12.
Am J Transplant ; 15(1): 234-41, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25534448

RESUMO

The clonal expansion of effector T cells and subsequent generation of memory T cells are critical in determining the outcome of transplantation. While cytotoxic T lymphocytes induce direct cytolysis of target cells through secretion of Granzyme-B (GrB), they also express cytoplasmic serine protease inhibitor-6 (Spi6) to protect themselves from GrB that has leaked from granules. Here, we studied the role of GrB/Spi6 axis in determining clonal expansion of alloreactive CD8-T cells and subsequent generation of memory CD8-T cells in transplantation. CD8-T cells from Spi6(-/-) mice underwent more GrB mediated apoptosis upon alloantigen stimulation in vitro and in vivo following adoptive transfer into an allogeneic host. Interestingly, while OT1.Spi6(-/-) CD8 T cells showed significantly lower clonal expansion following skin transplants from OVA mice, there was no difference in the size of the effector memory CD8-T cells long after transplantation. Furthermore, lack of Spi6 resulted in a decrease of short-lived-effector-CD8-cells but did not impact the pool of memory-precursor-effector-CD8-cells. Similar results were found in heart transplant models. Our findings suggest that the final alloreactive CD8-memory-pool-size is independent from the initial clonal-proliferation as memory precursors express low levels of GrB and therefore are independent of Spi6 for survival. These data advance our understanding of memory T cells generation in transplantation and provide basis for Spi6 based strategies to target effector T cells.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Doença Enxerto-Hospedeiro/imunologia , Transplante de Coração , Memória Imunológica/imunologia , Proteínas de Membrana/fisiologia , Serpinas/fisiologia , Transplante de Pele , Linfócitos T Citotóxicos/imunologia , Animais , Linfócitos T CD8-Positivos/patologia , Sobrevivência Celular/imunologia , Células Dendríticas/imunologia , Células Dendríticas/patologia , Doença Enxerto-Hospedeiro/patologia , Granzimas/fisiologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Linfócitos T Citotóxicos/patologia , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/patologia
13.
Phytopathology ; 105(7): 966-81, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25760519

RESUMO

Phytophthora infestans has been a named pathogen for well over 150 years and yet it continues to "emerge", with thousands of articles published each year on it and the late blight disease that it causes. This review explores five attributes of this oomycete pathogen that maintain this constant attention. First, the historical tragedy associated with this disease (Irish potato famine) causes many people to be fascinated with the pathogen. Current technology now enables investigators to answer some questions of historical significance. Second, the devastation caused by the pathogen continues to appear in surprising new locations or with surprising new intensity. Third, populations of P. infestans worldwide are in flux, with changes that have major implications to disease management. Fourth, the genomics revolution has enabled investigators to make tremendous progress in terms of understanding the molecular biology (especially the pathogenicity) of P. infestans. Fifth, there remain many compelling unanswered questions.


Assuntos
Interações Hospedeiro-Patógeno , Phytophthora infestans/fisiologia , Doenças das Plantas/história , Solanum lycopersicum/microbiologia , Solanum tuberosum/microbiologia , Genômica , História do Século XIX , História do Século XX , História do Século XXI , Doenças das Plantas/microbiologia
14.
Ann Oncol ; 25(10): 2047-2052, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25091317

RESUMO

BACKGROUND: Although advanced cutaneous squamous cell carcinoma (CSCC) is quite common, there are few prospective trials regarding its optimal management. This study evaluated the efficacy and safety of single-agent panitumumab in the treatment of patients with CSCC not suitable for local therapy. PATIENTS AND METHODS: Sixteen patients received single-agent panitumumab at a dose of 6 mg/kg repeated every 2 weeks for a minimum of three cycles and continued until progression, a maximum of nine cycles or dose-limiting toxicity. The primary end point was the best overall response rate (ORR) as assessed by Response Evaluation Criteria in Solid Tumours (RECIST version 1.1) criteria. Secondary end points included evaluation of safety, toxicity and progression-free survival (PFS). RESULTS: Between May 2010 and May 2012, 16 patients were recruited. Fourteen patients were male and the median age was 68 years. Fifteen patients had locoregionally advanced or recurrent disease with 14 patients receiving previous radiotherapy and 7 receiving previous cytotoxic chemotherapy. The best ORR [partial (PR) or complete response (CR)] was 31% (3/16 PR, 2/16 CR) with a further 6 of 16 patients achieving SD. The median PFS and overall survival were 8 and 11 months respectively. Grade 3 or 4 events were observed in five patients (four being skin toxicity) with one patient ceasing due to skin toxicity. With a median follow-up of 24 months, 10 patients died due to progressive disease, 6 are alive, one patient with no evidence of disease at the time of analysis. CONCLUSIONS: Single-agent panitumumab is safe and effective in the management of patients with advanced CSCC even in a previously extensively pre-treated cohort.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/efeitos adversos , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Intervalo Livre de Doença , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Panitumumabe , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia
15.
J Antimicrob Chemother ; 69(2): 292-302, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24072169

RESUMO

The emergence and spread of multidrug-resistant strains of Mycobacterium tuberculosis remains a major concern of tuberculosis control programmes worldwide, as treatment depends on low-efficacy, toxic compounds that often lead to poor outcomes. M. tuberculosis develops drug resistance exclusively through chromosomal mutations, in particular single-nucleotide polymorphisms. Moreover, in laboratory assays the organism exhibits a spontaneous mutation rate that is at the lower end of the bacterial spectrum. Despite this, whole-genome sequencing technology has identified unexpected genetic diversity among clinical M. tuberculosis populations. This suggests that the mycobacterial mutation rate may be modulated within the host and, in turn, implies a potential role for constitutive and/or transient mutator strains in adaptive evolution. It also raises the possibility that environmental factors might act as key mutagens during M. tuberculosis infection. Here we consider the elements that might influence the mycobacterial mutation rate in vivo and evaluate the potential roles of constitutive and transient mutator states in the generation of drug resistance mutations. In addition, we identify key research questions that will influence future efforts to develop novel therapeutic strategies for a disease that continues to impose a significant global health burden.


Assuntos
Antituberculosos , Farmacorresistência Bacteriana Múltipla/genética , Taxa de Mutação , Mycobacterium tuberculosis/genética , Tuberculose/genética , Tuberculose/microbiologia , Animais , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , Humanos , Mycobacterium tuberculosis/efeitos dos fármacos , Tuberculose/tratamento farmacológico
16.
J Chem Phys ; 141(24): 244505, 2014 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-25554165

RESUMO

We present a comprehensive simulation study on the solid-liquid phase transition of the ionic liquid 1,3-dimethylimidazolium chloride in terms of the changes in the atomic structure and their effect on the Compton profile. The structures were obtained by using ab initio molecular dynamics simulations. Chosen radial distribution functions of the liquid structure are presented and found generally to be in good agreement with previous ab initio molecular dynamics and neutron scattering studies. The main contributions to the predicted difference Compton profile are found to arise from intermolecular changes in the phase transition. This prediction can be used for interpreting future experiments.

17.
J Environ Qual ; 43(4): 1460-6, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25603093

RESUMO

Ozone (O) is implicated in the natural source inventory of ClO, a hydrophilic salt that migrates to groundwater and interferes with the uptake of iodide in mammals, including humans. Tropospheric O is elevated in many urban and some rural areas in the United States and globally. We previously showed that controlled O exposure at near-ambient concentrations (up to 114 nL L, 12-h mean) did not increase foliar ClO. Under laboratory conditions, O has been shown to oxidize Cl to ClO. Plant tissues contain Cl and exhibit responses to O invoking redox reactions. As higher levels of O are associated with stratospheric incursion and with developing megacities, we have hypothesized that exposure of vegetation to such elevated O may increase foliar ClO. This would contribute to ClO in environments without obvious point sources. At these high O concentrations (up to 204 nL L, 12-h mean; 320 nL L maximum), we demonstrated an increase in the ClO concentration in surface soil that was linearly related to the O concentration. There was no relationship of foliar ClO with O exposure or dose (stomatal uptake). Accumulation of ClO varied among species at low O, but this was not related to soil surface ClO or to foliar ClO concentrations following exposure to O. These data extend our previous conclusions to the highest levels of plausible O exposure, that tropospheric O contributes to environmental ClO through interaction with the soil but not through increased foliar ClO.

18.
Plant Dis ; 97(3): 296-306, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30722376

RESUMO

The tomato late blight pandemic of 2009 made late blight into a household term in much of the eastern United States. Many home gardeners and many organic producers lost most if not all of their tomato crop, and their experiences were reported in the mainstream press. Some CSAs (Community Supported Agriculture) could not provide tomatoes to their members. In response, many questions emerged: How did it happen? What was unusual about this event compared to previous late blight epidemics? What is the current situation in 2012 and what can be done? It's easiest to answer these questions, and to understand the recent epidemics of late blight, if one knows a bit of the history of the disease and the biology of the causal agent, Phytophthora infestans.

19.
Arch Dermatol Res ; 315(7): 2139-2143, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36369596

RESUMO

Skin and soft tissue infections (SSTIs) have high rates of morbidity and mortality worldwide but lack reliable standards for diagnostic workup. As a result, atypical infections, more prevalent among immunocompromised patients, can be missed due to deviance from classic features only to be revealed later through inconsistently performed ancillary studies. Our objectives included to evaluate the sensitivities of clinical impression, histopathology, tissue culture, and molecular and non-molecular ancillary tests in diagnosing inpatient SSTIs, as well as to qualitatively discuss the unusual features making a subset of infections "atypical." To do so, we retrospectively reviewed the histopathologic reports and charts of inpatient dermatologic consults at a single tertiary care institution over a 3-year period. We identified a total of 111 cases of SSTIs evaluated by the inpatient dermatology consultation service with concurrent skin or soft tissue biopsy, with 32.4% representing atypical infections. Among these, clinical impression suggested infection in 9(25.0%), routine histopathology in 21(58.3%), specialized stains for microorganisms in 22(68.8%), and tissue culture in 15(68.2%). Due to incomplete picture that each modality by itself creates, we conclude that clinicians and pathologists should carry a low threshold for including SSTIs in their differential diagnoses and should evaluate with skin biopsy, special stains for microorganisms, and ancillary studies, particularly in critically ill individuals who necessitate timely diagnoses.

20.
Public Health ; 126(1): 12-7, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22130477

RESUMO

OBJECTIVES: This study identified and reviewed grey literature relating to factors facilitating and inhibiting effective interventions in three areas: the promotion of mental health and well-being, the improvement of food and nutrition, and interventions seeking to increase engagement in physical activity. STUDY DESIGN: Sourcing, reviewing and analysis of relevant grey literature. METHODS: Evidence was collected from a variety of non-traditional sources. Thirty-six pieces of documentary evidence across the three areas were selected for in-depth appraisal and review. RESULTS: A variety of approaches, often short-term, were used both as interventions and outcome measures. Interventions tended to have common outcomes, enabling the identification of themes. These included improvements in participant well-being as well as identification of barriers to, and promoters of, success. Most interventions demonstrated some positive impact, although some did not. This was particularly the case for more objective measures of change, such as physiological measurements, particularly when used to evaluate short-term interventions. Objective health measurement as part of an intervention may act as a catalyst for future behaviour change. Time is an important factor that could either promote or impede the success of interventions for both participants and facilitators. Likewise, the importance of involving all stakeholders, including participants, when planning health promoting interventions was established as an important indicator of success. DISCUSSION: Despite its limited scope, this review suggests that interventions can be more efficient and effective. For example, larger-scale, longer-term interventions could be more efficient, whilst outcomes relating to the implementation and beyond could provide a clearer picture of effectiveness. Additionally, interventions and evaluations must be flexible, evolve in partnership with local communities, and reflect local need and context.


Assuntos
Exercício Físico/fisiologia , Comportamentos Relacionados com a Saúde , Promoção da Saúde , Saúde Mental , Fenômenos Fisiológicos da Nutrição , Serviços Preventivos de Saúde , Humanos , Saúde Pública , Comportamento de Redução do Risco
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