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Compassionate conservation is based on the ethical position that actions taken to protect biodiversity should be guided by compassion for all sentient beings. Critics argue that there are 3 core reasons harming animals is acceptable in conservation programs: the primary purpose of conservation is biodiversity protection; conservation is already compassionate to animals; and conservation should prioritize compassion to humans. We used argument analysis to clarify the values and logics underlying the debate around compassionate conservation. We found that objections to compassionate conservation are expressions of human exceptionalism, the view that humans are of a categorically separate and higher moral status than all other species. In contrast, compassionate conservationists believe that conservation should expand its moral community by recognizing all sentient beings as persons. Personhood, in an ethical sense, implies the individual is owed respect and should not be treated merely as a means to other ends. On scientific and ethical grounds, there are good reasons to extend personhood to sentient animals, particularly in conservation. The moral exclusion or subordination of members of other species legitimates the ongoing manipulation and exploitation of the living worlds, the very reason conservation was needed in the first place. Embracing compassion can help dismantle human exceptionalism, recognize nonhuman personhood, and navigate a more expansive moral space.
Reconocimiento de la Calidad de Persona en los Animales dentro de la Conservación Compasiva Resumen La conservación compasiva está basada en la posición ética que parte de que las acciones tomadas para proteger a la biodiversidad deberían estar dirigidas por la compasión por todos los seres sintientes. Los críticos de esta postura argumentan que hay tres razones nucleares por las que el daño a los animales es aceptable dentro de los programas de conservación: el principal motivo de la conservación es la protección de la biodiversidad; la conservación ya es compasiva con los animales; y la conservación debería priorizar la compasión hacia los humanos. Usamos un análisis de argumentos para aclarar los valores y la lógica subyacentes al debate en torno a la conservación compasiva. Encontramos que el rechazo a la conservación compasiva es una expresión de la excepcionalidad humana, la visión de que los humanos están en un nivel categóricamente separado y de mayor moral que todas las demás especies. Por el contrario, los conservacionistas compasivos creen que la conservación debería expandir su comunidad moral al reconocer a todos los seres sintientes como personas. La calidad de persona, en un sentido ético, implica que el individuo merece respeto y no debería ser tratado solamente como un medio para otros fines. Si hablamos desde fundamentos científicos y éticos, existen muy buenas razones para extender la calidad de persona a todos los animales sintientes, particularmente en la conservación. La exclusión moral o la subordinación de los miembros de otras especies justifica la continua manipulación y explotación de los seres vivos, la justa razón por la que necesitamos de la conservación desde el principio. La aceptación de la compasión nos puede ayudar a desmantelar la excepcionalidad humana, a reconocer la calidad de persona no humana y a navegar un espacio moral más expansivo.
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Conservação dos Recursos Naturais , Pessoalidade , Animais , Biodiversidade , Empatia , Humanos , Princípios MoraisRESUMO
Some conservationists believe that free-ranging cats pose an enormous risk to biodiversity and public health and therefore should be eliminated from the landscape by any means necessary. They further claim that those who question the science or ethics behind their arguments are science deniers (merchants of doubt) seeking to mislead the public. As much as we share a commitment to conservation of biodiversity and wild nature, we believe these ideas are wrong and fuel an unwarranted moral panic over cats. Those who question the ecological or epidemiological status of cats are not science deniers, and it is a false analogy to compare them with corporate and right-wing special interests that perpetrate disinformation campaigns over issues, such as smoking and climate change. There are good conservation and public-health reasons and evidence to be skeptical that free-ranging cats constitute a disaster for biodiversity and human health in all circumstances. Further, there are significant and largely unaddressed ethical and policy issues (e.g., the ethics and efficacy of lethal management) relative to how people ought to value and coexist with cats and native wildlife. Society is better served by a collaborative approach to produce better scientific and ethical knowledge about free-ranging cats.
Pánico Moral por los Gatos Resumen Algunos conservacionistas creen que los gatos sueltos representan un riesgo enorme para la biodiversidad y la salud pública, por lo que deberían ser eliminados del paisaje a como dé lugar. Los conservacionistas además alegan que quienes cuestionan la ciencia o la ética detrás de estos argumentos son negadores de la ciencia (mercaderes de la duda) que buscan desinformar al público. Por mucho que compartamos un compromiso con la conservación de la biodiversidad y la fauna silvestre, creemos que estás ideas están equivocadas y alimentan un pánico moral injustificado por los gatos. Aquellos que cuestionan el estado ecológico o epidemiológico de los gatos no son negadores de la ciencia y es una analogía falsa compararlos con los intereses especiales de los corporativos y de la derecha política, los cuales perpetúan las campañas de desinformación de temas como el cigarro y el cambio climático. Existen razones y evidencias de conservación y salud pública para ser escépticos sobre el argumento de que los gatos sueltos constituyen un desastre para la biodiversidad y la salud humana bajo todas las circunstancias. Además, hay temas éticos y políticos que no reciben atención (p. ej.: la ética y la eficacia del manejo letal) relativos a cómo las personas deberían valorar y coexistir con los gatos y la fauna nativa. La sociedad se beneficia más con una estrategia colaborativa para producir un mejor conocimiento científico y ético sobre los gatos que viven sueltos.
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Biodiversidade , Conservação dos Recursos Naturais , Animais , Animais Selvagens , Gatos , Humanos , Princípios MoraisRESUMO
We previously determined the extent to which mutations of different Staphylococcus aureus regulatory loci impact biofilm formation as assessed under in vitro conditions. Here we extend these studies to determine the extent to which those regulatory loci that had the greatest effect on biofilm formation also impact antibiotic susceptibility. The experiments were done under in vitro and in vivo conditions using two clinical isolates of S. aureus (LAC and UAMS-1) and two functionally diverse antibiotics (daptomycin and ceftaroline). Mutation of the staphylococcal accessory regulator (sarA) or sigB was found to significantly increase susceptibilities to both antibiotics and in both strains in a manner that could not be explained by changes in the MICs. The impact of a mutation in sarA was comparable to that of a mutation in sigB and greater than the impact observed with any other mutant. These results suggest that therapeutic strategies targeting sarA and/or sigB have the greatest potential to facilitate the ability to overcome the intrinsic antibiotic resistance that defines S. aureus biofilm-associated infections.
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Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Biofilmes/efeitos dos fármacos , Cefalosporinas/farmacologia , Daptomicina/farmacologia , Fator sigma/genética , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/genética , Animais , Biofilmes/crescimento & desenvolvimento , Infecções Relacionadas a Cateter/tratamento farmacológico , Infecções Relacionadas a Cateter/microbiologia , Catéteres/microbiologia , Farmacorresistência Bacteriana/genética , Humanos , Camundongos , Testes de Sensibilidade Microbiana , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/isolamento & purificação , Staphylococcus aureus/patogenicidade , CeftarolinaRESUMO
We used in vitro and in vivo models of catheter-associated biofilm formation to compare the relative activity of antibiotics effective against methicillin-resistant Staphylococcus aureus (MRSA) in the specific context of an established biofilm. The results demonstrated that, under in vitro conditions, daptomycin and ceftaroline exhibited comparable activity relative to each other and greater activity than vancomycin, telavancin, oritavancin, dalbavancin, or tigecycline. This was true when assessed using established biofilms formed by the USA300 methicillin-resistant strain LAC and the USA200 methicillin-sensitive strain UAMS-1. Oxacillin exhibited greater activity against UAMS-1 than LAC, as would be expected, since LAC is an MRSA strain. However, the activity of oxacillin was less than that of daptomycin and ceftaroline even against UAMS-1. Among the lipoglycopeptides, telavancin exhibited the greatest overall activity. Specifically, telavancin exhibited greater activity than oritavancin or dalbavancin when tested against biofilms formed by LAC and was the only lipoglycopeptide capable of reducing the number of viable bacteria below the limit of detection. With biofilms formed by UAMS-1, telavancin and dalbavancin exhibited comparable activity relative to each other and greater activity than oritavancin. Importantly, ceftaroline was the only antibiotic that exhibited greater activity than vancomycin when tested in vivo in a murine model of catheter-associated biofilm formation. These results emphasize the need to consider antibiotics other than vancomycin, most notably, ceftaroline, for the treatment of biofilm-associated S. aureus infections, including by the matrix-based antibiotic delivery methods often employed for local antibiotic delivery in the treatment of these infections.
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Antibacterianos/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Aminoglicosídeos/farmacologia , Animais , Biofilmes/efeitos dos fármacos , Infecções Relacionadas a Cateter/tratamento farmacológico , Infecções Relacionadas a Cateter/microbiologia , Avaliação Pré-Clínica de Medicamentos/métodos , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Glicopeptídeos/farmacologia , Lipoglicopeptídeos , Staphylococcus aureus Resistente à Meticilina/patogenicidade , Camundongos , Testes de Sensibilidade Microbiana , Teicoplanina/análogos & derivados , Teicoplanina/farmacologiaRESUMO
PURPOSE: To determine factors affecting the visual outcome of eyes with endogenous Candida endophthalmitis. METHODS: Retrospective cohort study of 44 eyes from 36 patients diagnosed with candida endophthalmitis at 2 tertiary referral uveitis centers. Outcome measures included the development of retinal detachment and the occurrence of visual loss (visual acuity of <20/40) and severe visual loss (visual acuity of ≤ 20/200). RESULTS: Twenty four of 44 eyes (55%) had visual loss and 16 of 44 eyes (32%) had severe visual loss by the end of the study. Early vitrectomy significantly reduced the risk of retinal detachment (P = 0.02). Factors associated with poor visual outcome included poor presenting visual acuity (relative risk = 2.38; 95% confidence interval, 1.01-5.55; P < 0.05) and centrally located fungal lesions (relative risk = 5.01; 95% confidence interval, 1.00-2.52; P < 0.05). CONCLUSION: Candida endophthalmitis is associated with a high rate of visual loss, particularly in patients with poor presenting visual acuity or centrally located lesions. Early vitrectomy reduces the risk of retinal detachment.
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Candida/isolamento & purificação , Endoftalmite/microbiologia , Infecções Oculares Fúngicas/microbiologia , Acuidade Visual/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Endoftalmite/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Descolamento Retiniano/prevenção & controle , Estudos Retrospectivos , Fatores de Risco , VitrectomiaRESUMO
Although human interactions with cats are often even typically analyzed in the context of domesticity, with a focus on what sorts of interactions might make both people and cats "happy at home," a large number of cats in the world live, for one reason or another, beyond the bounds of domesticity. Human interactions with these more or less free-living cats raise deeply controversial questions about how both the cats and the people they interact with should be sensibly managed, and about the moral imperatives that ought to guide the management of their interactions through the laws and public policies regulating both human interactions with pets and with wildlife. We review the geography of human interactions with cats living beyond the bounds of domesticity. We acknowledge the contributions made to ideas about how to manage cats by the animal protection movement. We review the tensions that have emerged over time between advocates for the eradication of free-living cats, because of the impacts they have on native wildlife species, and those who have imagined alternatives to eradication, most notably one or another variant of trap-neuter-return (TNR). The conflict over how best to deal with cats living beyond the bounds of domesticity and their wildlife impacts raises the prospect of stalemate, and we canvass and critique possibilities for moving beyond that stalemate.
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OBJECTIVE: Tuberculosis Drug Induced Liver Injury (TB-DILI) is a common and potentially severe complication associated with anti-tuberculous treatment (ATT). Optimal liver test monitoring for standard TB medication has not been established. We describe the predictive value of pre-treatment liver tests (LTs) and at 2-weeks after initiation of ATT for the detection of TB-DILI. METHODS: Patients initiating ATT were monitored with routine LTs pre-treatment and after 2-weeks. Logistic regression models were constructed to retrospectively identify pre-treatment variables associated with 'late' TB-DILI (>2 weeks after treatment initiation) and whether pre-treatment and 2-week alanine aminotransferase (ALT) levels could predict late TB-DILI. RESULTS: 1247 patients with active tuberculosis managed at 5 sites across north west London between January 2015 and December 2018 were monitored with routine LTs. 103 cases (8.3%) of ATT-associated DILI were diagnosed. 60 cases (58.3%) of TB-DILI occurred later than 2-weeks. The risk of late TB-DILI was 2.2-fold greater for every 30â¯U/L increment in ALT pre-treatment (OR 2.16, 95% CI 1.38-3.29 p<0.001) and 2.1-fold greater for every 30â¯U/L increment in ALT gradient at 2-weeks (OR 2.06, 95% CI 1.52-2.76 p<0.001). CONCLUSION: Routine 2-week LTs capture early TB-DILI and may be valuable in predicting late TB-DILI in patients on ATT.
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Doença Hepática Induzida por Substâncias e Drogas , Tuberculose , Antituberculosos/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Humanos , Londres , Estudos Retrospectivos , Tuberculose/diagnóstico , Tuberculose/tratamento farmacológicoRESUMO
BACKGROUND: The World Health Organisation states that the chest x-ray (CXR) has a 'high sensitivity for pulmonary tuberculosis (TB)' [1] and as such, is relied on worldwide as the cornerstone of screening for active pulmonary TB (pTB). METHOD: This is a retrospective analysis of plain chest radiographs and microbiological yield in all patients who were diagnosed with pTB or intra-thoracic nodal tuberculosis (ITLN) in two London NHS Trusts. RESULTS: Between 2011 and 2017 8% of those diagnosed with pTB and 32% with ITLN TB had normal CXR appearances in the 6 weeks preceding diagnosis. DISCUSSION: Pulmomary TB was diagnosed in an additional 51 people based on CT scan and 43 people based on respiratory samples. ITLN TB was also diagnosed in a further 20 people using CT but only an extra 3 people from standard respiratory sampling. Our data suggests that CT imaging and respiratory samples should be sent on all suspected cases of pTB and ITLN TB even if the CXR is normal.
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Líquido da Lavagem Broncoalveolar/microbiologia , Mycobacterium tuberculosis/isolamento & purificação , Escarro/microbiologia , Tuberculose Pulmonar/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase/métodos , Radiografia Torácica , Estudos Retrospectivos , Sensibilidade e Especificidade , Tomografia Computadorizada por Raios X , Tuberculose Pulmonar/diagnóstico por imagem , Adulto JovemRESUMO
BACKGROUND: Colonoscopy is the gold-standard investigation for direct luminal visualization of the large bowel. Studies have shown the efficacy of computed tomography colonography (CTC) is equivalent to colonoscopy in both cancer and polyp detection. METHODS: A retrospective review of patients undergoing CTC from January 2013 to October 2014 was performed. Patient demographics, indication for investigation, computed tomography findings, optical colonoscopy findings and histology results were recorded. RESULTS: Seven hundred and fifty-eight CTC were performed. Three hundred and seventeen patients were male (42%) and 441 (58%) were female. Endoscopy was advised in 209 cases. One hundred and twenty (16%) were deemed suspicious for cancer of whom 96 (80%) had optical colonoscopy. A total of 12 colorectal cancers were detected. Potential polyps were noted in 58 cases (8%). Forty-four patients underwent endoscopy (75%) and 17 polyps confirmed (38%). Two patients had foci of invasive cancer histologically. Significant extracolonic findings were identified in 60%, including five cases of gastric carcinomas. The most common other findings were gallstones and hernias. CONCLUSION: The rate of colorectal cancer detection in this study was 2%. The rate of biopsy proven cancer was 10% following a suspicious colonogram. Endoscopic correlation was not obtained in 20% of cases of radiological suspicion. CTC is as efficacious as optical colonoscopy for colorectal cancer and polyp detection.
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Colonografia Tomográfica Computadorizada/métodos , Neoplasias Colorretais/diagnóstico , Hospitais de Distrito , Hospitais Gerais , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Colonoscopia , Diagnóstico Diferencial , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Estudos Retrospectivos , Fatores de Tempo , Adulto JovemRESUMO
BACKGROUND AND OBJECTIVES: Laparoscopic sleeve gastrectomy (LSG) has some unique complications, the most concerning of which is sleeve leak. Staple line reinforcement (SLR) has been suggested as a means of decreasing the risk of sleeve leak, but it increases the cost. However, there is little in the literature regarding the effect of standardized operative technique in reducing the complications and improving the outcomes in LSG. We sought to demonstrate that standardization of the operative procedure and perioperative care is the key to an excellent 30-day outcome and that SLR is not necessary to ensure a negligible staple line leak and bleeding rate. METHODS: A prospectively maintained database was analyzed to identify 303 consecutive patients undergoing LSG between July 2010 and November 2017. Data on patient demographics, length of hospital stay, conversion to open surgery, perioperative complications, and mortality were analyzed. Standardized operative technique and postoperative protocol were followed in all cases. SLR was not used in any case. RESULTS: Among 303 cases, there were 15 complications (5%), 5 (1.7%) of which were severe (Clavien-Dindo grade ≥3a). There were no conversions to open procedure, no staple line leaks, and no inpatient deaths in the cohort. No patient was readmitted with an early stricture. CONCLUSIONS: The use of a standardized operative and postoperative protocol led to an excellent early outcome in our LSG cases. Standardization may act to obviate the need for routine SLR techniques which are associated with a significant financial cost to both patient and hospital.
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Fístula Anastomótica/prevenção & controle , Gastrectomia/normas , Laparoscopia/normas , Obesidade Mórbida/cirurgia , Adulto , Bases de Dados Factuais , Feminino , Gastrectomia/métodos , Humanos , Laparoscopia/métodos , Masculino , Pessoa de Meia-Idade , Assistência Perioperatória/métodos , Assistência Perioperatória/normas , Grampeamento Cirúrgico/métodos , Grampeamento Cirúrgico/normas , Resultado do TratamentoRESUMO
Oesophageal adenocarcinoma following gastric band surgery has only been reported three times previously. The incidence is higher in morbidly obese patients, and its pathogenesis is correlated to reflux-induced microenvironmental changes. Bariatric surgery is transformative and its potential benefit for a substantial population is huge. Although no causal relationship with bariatric procedures has been evidenced to date, symptoms of adenocarcinoma-particularly anorexia, weight loss and dysphagia-can easily be overshadowed by alterations in eating patterns associated with weight-loss procedures. We report two cases of oesophageal adenocarcinoma in patients who had undergone a gastric banding procedure, and invite readers to consider the role that pre- and post-operative acid reflux dynamics may have precipitating neoplastic disease, and how endoscopic surveillance may play a role in prevention.
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The original Article mistakenly coded the constitutional rights of Australia as containing a governmental duty to protect the environment (blue in the figures); this has been corrected to containing no explicit mention of environmental protection (orange in the figures). The original Article also neglected to code the constitutional rights of the Cayman Islands (no data; yellow in the figures); this has been corrected to containing a governmental duty to protect the environment (blue in the figures).Although no inferences changed as a result of these errors, many values changed slightly and have been corrected. The proportion of the world's nations having constitutional rights to a healthy environment changed from 75% to 74%. The proportions of nations in different categories given in the Fig. 1 caption all changed except purple countries (3.1%): green countries changed from 47.2% to 46.9%; blue countries changed from 24.4% to 24.2%; and orange countries changed from 25.3% to 25.8%. The proportion of the global atmospheric CO2 emitted by the 144 nations changed from 72.6% to 74.4%; the proportion of the world's population represented by the 144 nations changed from 84.9% to 85%. The values of annual average CO2 emissions for blue countries changed from 363,000 Gg to 353,000 Gg and for orange countries from 195,000 Gg to 201,000 Gg. The proportion of threatened mammals endemic to a single country represented by the 144 countries changed from 91% to 84%. Figures 1-3 have been updated to show the correct values and map colours and the Supplementary Information has been updated to give the correct country codes.
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BACKGROUND: Tackling tuberculosis requires testing and treatment of latent tuberculosis in high-risk groups. The aim of this study was to estimate the predictive values of the tuberculin skin test (TST) and two interferon-γ release assays (IGRAs) for the development of active tuberculosis in high-risk groups-ie, people in recent contact with active tuberculosis cases and from high-burden countries. METHOD: In this prospective cohort study, we recruited participants from 54 centres (eg, clinics, community settings) in London, Birmingham, and Leicester in the UK. Participants were eligible if they were aged 16 years or older and at high risk for latent tuberculosis infection (ie, recent contact with someone with active tuberculosis [contacts] or a migrant who had arrived in the UK in the past 5 years from-or who frequently travelled to-a country with a high burden of tuberculosis [migrants]). Exclusion criteria included prevalent cases of tuberculosis, and participants who were treated for latent tuberculosis after a positive test result in this study. Each participant received three tests (QuantiFERON-TB Gold-In Tube, T-SPOT.TB, and a Mantoux TST). A positive TST result was reported using three thresholds: 5 mm (TST-5), 10 mm (TST-10), and greater than 5 mm in BCG-naive or 15 mm in BCG-vaccinated (TST-15) participants. Participants were followed up from recruitment to development of tuberculosis or censoring. Incident tuberculosis cases were identified by national tuberculosis databases, telephone interview, and review of medical notes. Our primary objective was to estimate the prognostic value of IGRAs compared with TST, assessed by the ratio of incidence rate ratios and predictive values for tuberculosis development. The study was registered with ClinicalTrials.gov, NCT01162265, and is now complete. FINDINGS: Between May 4, 2010, and June 1, 2015, 10â045 people were recruited, of whom 9610 were eligible for inclusion. Of this cohort, 4861 (50·6%) were contacts and 4749 (49·4%) were migrants. Participants were followed up for a median of 2·9 years (range 21 days to 5·9 years). 97 (1·0%) of 9610 participants developed active tuberculosis (77 [1·2%] of 6380 with results for all three tests). In all tests, annual incidence of tuberculosis was very low in those who tested negatively (ranging from 1·2 per 1000 person-years, 95% CI 0·6-2·0 for TST-5 to 1·9 per 1000 person-years, 95% CI 1·3-2·7, for QuantiFERON-TB Gold In-Tube). Annual incidence in participants who tested positively were highest for T-SPOT.TB (13·2 per 1000 person-years, 95% CI 9·9-17·4), TST-15 (11·1 per 1000 person-years, 8·3-14·6), and QuantiFERON-TB Gold In-Tube (10·1 per 1000 person-years, 7·4-13·4). Positive results for these tests were significantly better predictors of progression than TST-10 and TST-5 (eg, ratio of test positivity rates in those progressing to tuberculosis compared with those not progressing T-SPOT.TB vs TST-5: 1·99, 95% CI 1·68-2·34; p<0·0001). However, TST-5 identified a higher proportion of participants who progressed to active tuberculosis (64 [83%] of 77 tested) than all other tests and TST thresholds (≤75%). INTERPRETATION: IGRA-based or BCG-stratified TST strategies appear most suited to screening for potential disease progression among high-risk groups. Further work will be needed to assess country-specific cost-effectiveness of each screening test, and in the absence of highly specific diagnostic tests, cheap non-toxic treatments need to be developed that could be given to larger groups of people at potential risk. FUNDING: National Institute for Health Research Health Technology Assessment Programme 08-68-01.
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Testes de Liberação de Interferon-gama , Teste Tuberculínico , Tuberculose/diagnóstico , Adulto , Vacina BCG/imunologia , Feminino , Guias como Assunto , Humanos , Masculino , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Tuberculose/prevenção & controle , Reino UnidoRESUMO
We have previously demonstrated that spontaneous DNA synthesis in immature thymocytes of Atm-/- mice is elevated, and that treatment with the glucocorticoid dexamethasone (Dex) attenuates this increased DNA synthesis and prevents the development of thymic lymphomas. Deregulation of c-myc may drive the uncontrolled proliferation of Atm-/- thymocytes, since upregulation of c-myc parallels the elevated DNA synthesis in the cells. In this study, we show that the glucocorticoid receptor (GR) is expressed at high levels in Atm-/- thymocytes and in Atm-/- thymic lymphoma cells, although serum glucocorticoid (GC) levels in Atm-/- mice are similar to those in Atm+/+ mice. In cultured Atm-/- thymic lymphoma cells treated with Dex, GR nuclear translocation occurs, resulting in suppression of DNA synthesis and c-myc expression at both the mRNA and protein levels. Interestingly, the GR antagonist RU486 also causes GR nuclear translocation, but does not affect DNA synthesis and c-myc expression in Atm-/- thymic lymphoma cells. As expected, RU486 reverses the suppressive effects of Dex on DNA synthesis and c-myc expression. Administration of Dex to Atm-/- mice decreases the elevated c-Myc protein levels in their thymocytes. These findings suggest that GC/GR signaling plays an important role in regulating c-myc expression in Atm-/- thymocytes and thymic lymphoma cells.
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Núcleo Celular/metabolismo , Proteínas de Ligação a DNA/deficiência , Regulação Leucêmica da Expressão Gênica , Linfoma/metabolismo , Proteínas Serina-Treonina Quinases/deficiência , Proteínas Proto-Oncogênicas c-myc/biossíntese , Receptores de Glucocorticoides/metabolismo , Timo/metabolismo , Proteínas Supressoras de Tumor/deficiência , Transporte Ativo do Núcleo Celular/efeitos dos fármacos , Transporte Ativo do Núcleo Celular/genética , Animais , Antineoplásicos Hormonais/farmacologia , Proteínas Mutadas de Ataxia Telangiectasia , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Núcleo Celular/genética , DNA/biossíntese , Proteínas de Ligação a DNA/metabolismo , Dexametasona/farmacologia , Regulação Leucêmica da Expressão Gênica/efeitos dos fármacos , Regulação Leucêmica da Expressão Gênica/genética , Antagonistas de Hormônios/farmacologia , Linfoma/genética , Linfoma/patologia , Camundongos , Camundongos Knockout , Mifepristona/farmacologia , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas c-myc/genética , Receptores de Glucocorticoides/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Timo/patologia , Proteínas Supressoras de Tumor/metabolismoRESUMO
The aim of this study was to determine the current outcome of gunshots to the arteries of the lower extremity. The authors conducted a retrospective analysis of 104 patients with gunshots to the femoral (n=71) and popliteal (n=33) artery. One hundred four patients presented over the 60-month period. Ninety-six (92%) were male and eight of 104 female. Ninety-nine were gunshot injuries, five from shotguns. Nine patients had injury to the common femoral artery, 62 patients had injury to the superficial femoral artery, and 33 had popliteal artery injury. One patient died in the emergency room and another died in the postoperative period, giving an overall in-hospital mortality of two of 104 (1.9%). Forty-three of 70 femoral reconstructions had completion angiograms compared with 20 of 32 popliteal artery reconstructions (P=1). Nineteen of 63 (30%) of the completion angiograms prompted revision of the reconstruction. Of the 63 patients who had completion angiograms, two of 63 (3%) required amputation. Seven of 39 (18%) patients who did not have completion angiograms required amputation (P = 0.025). Including the primary amputation, there were 10 amputations in the 103 patients (9.7%) who survived to undergo operation. Ballistic arterial trauma of the lower limb leads to significant disability. Completion arteriography leads to revision of the reconstruction in nearly one-third of instances and significantly reduces amputation rate.
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Artéria Femoral/lesões , Artéria Poplítea/lesões , Procedimentos Cirúrgicos Vasculares/métodos , Ferimentos por Arma de Fogo/cirurgia , Angiografia , Feminino , Artéria Femoral/diagnóstico por imagem , Artéria Femoral/cirurgia , Seguimentos , Humanos , Incidência , Masculino , Artéria Poplítea/diagnóstico por imagem , Artéria Poplítea/cirurgia , Estudos Retrospectivos , África do Sul/epidemiologia , Taxa de Sobrevida , Índices de Gravidade do Trauma , Ferimentos por Arma de Fogo/diagnóstico por imagem , Ferimentos por Arma de Fogo/epidemiologiaRESUMO
All the management options for thyrotoxicosis have advantages and disadvantages. It is important to have a full discussion with the patient to ensure that a treatment option is selected that is tailored to the individual.
Assuntos
Hipertireoidismo , Antitireóideos/uso terapêutico , Humanos , Hipertireoidismo/diagnóstico , Hipertireoidismo/etiologia , Hipertireoidismo/terapia , Radioisótopos do Iodo/uso terapêutico , Compostos Radiofarmacêuticos/uso terapêutico , Abandono do Hábito de Fumar , Tireoidite/etiologia , Tireoidite/prevenção & controle , Tireotoxicose/terapiaRESUMO
The oncoprotein c-Myc is essential for thymocyte development, and its dysregulation causes lymphoid malignancies. We have demonstrated previously that spontaneous DNA synthesis in Atm(-/-) thymocytes is markedly increased over that of Atm(+/+) thymocytes and that glucocorticoid dexamethasone suppresses thymocyte DNA synthesis and prevents the ultimate development of thymic lymphoma in Atm(-/-) mice. Recently, we reported that in Atm(-/-) thymic lymphoma cells c-Myc is overexpressed compared with the levels of c-Myc in primary thymocytes from wild-type or Atm(-/-) mice. In this study, we show that c-Myc expression progressively increases with age in primary thymocytes from Atm(-/-) mice and that the upregulation of c-Myc parallels the elevated DNA synthesis in the cells, suggesting that deregulation of c-Myc may drive the uncontrolled proliferation of thymocytes in Atm(-/-) mice. Here we also demonstrate that Atm(-/-) thymocytes exhibit increased levels of hydrogen peroxide, NF-E2-related factor (Nrf-2), peroxiredoxin-1, and intracellular glutathione relative to thymocytes from Atm(+/+) mice. Importantly, reduction of hydrogen peroxide by administration of the antioxidant N-acetylcysteine to Atm(-/-) mice attenuates the elevation of Nrf-2, c-Myc, and DNA synthesis in their thymocytes, suggesting that ATM may control c-Myc and DNA synthesis during postnatal thymocyte development by preventing accumulation of reactive oxygen species.