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Public health monitoring of Community Water Fluoridation (CWF) schemes requires estimates of exposure to fluoride in public water supplies (PWS). We aimed to use routine data to estimate population exposure to PWS-fluoride in England and to determine whether PWS-fluoride exposure from 2005 to 2015 could be used as a proxy for exposure for 1995-2004, when fluoride concentration data that could be linked to population health data were unavailable. We calculated annual mean water supply zone PWS-fluoride concentrations from monitoring data for 1995-2015, stratified by fluoridation scheme-flagging. We allocated annual 2005-2015 mean PWS-fluoride concentrations to small area boundaries to describe population exposure within five concentration categories (< 0.1 to ≥ 0.7 mg/L). We compared zone-level 1995-2004 and 2005-2015 mean PWS-fluoride concentrations using Spearman correlation. Most (72%) of the population received PWS with < 0.2 mg/L fluoride and 10% with ≥ 0.7 mg/L. Fluoride concentrations in 1995-2004 and 2005-2015 were similar (median 0.11 mg/L (lower quartile-upper quartile (LQ-UQ) 0.06-0.17) and 0.11 mg/L (LQ-UQ 0.07-0.17), respectively) and highly correlated (coefficient 0.93) if un-fluoridated but differed (1995-2004 median 0.78 mg/L (LQ-UQ 0.59-0.92); 2005-2015 0.84 mg/L (LQ-UQ 0.72-0.95)) and correlated weakly (coefficient 0.31) if fluoridated. Fluoride concentrations in 2005-2015 approximate those in 1995-2004 but with a greater risk of misclassification in fluoridation schemes.
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Monitoramento Ambiental , Fluoretos/análise , Inglaterra , Fluoretação , Abastecimento de ÁguaRESUMO
Background: MET exon 14 alterations are actionable oncogenic drivers. Durable responses to MET inhibitors are observed in patients with advanced MET exon 14-altered lung cancers in prospective trials. In contrast, the activity of immunotherapy, PD-L1 expression and tumor mutational burden (TMB) of these tumors and are not well characterized. Patients and methods: Patients with MET exon 14-altered lung cancers of any stage treated at two academic institutions were identified. A review of clinicopathologic and molecular features, and an analysis of response to single-agent or combination immune checkpoint inhibition were conducted. PD-L1 immunohistochemistry was carried out and TMB was calculated by estimation from targeted next-generation sequencing panels. Results: We identified 147 patients with MET exon 14-altered lung cancers. PD-L1 expression of 0%, 1%-49%, and ≥50% were 37%, 22%, and 41%, respectively, in 111 evaluable tumor samples. The median TMB of MET exon 14-altered lung cancers was lower than that of unselected non-small-cell lung cancers (NSCLCs) in both independently evaluated cohorts: 3.8 versus 5.7 mutations/megabase (P < 0.001, n = 78 versus 1769, cohort A), and 7.3 versus 11.8 mutations/megabase (P < 0.001, n = 62 versus 1100, cohort B). There was no association between PD-L1 expression and TMB (Spearman's rho=0.18, P = 0.069). In response-evaluable patients (n = 24), the objective response rate was 17% (95% CI 6% to 36%) and the median progression-free survival was 1.9 months (95% CI 1.7-2.7). Responses were not enriched in tumors with PD-L1 expression ≥50% nor high TMB. Conclusion: A substantial proportion of MET exon 14-altered lung cancers express PD-L1, but the median TMB is lower compared with unselected NSCLCs. Occasional responses to PD-1 blockade can be achieved, but overall clinical efficacy is modest.
Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Antígeno B7-H1/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Éxons/genética , Neoplasias Pulmonares/patologia , Mutação , Proteínas Proto-Oncogênicas c-met/genética , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno B7-H1/antagonistas & inibidores , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Estudos de Coortes , Feminino , Seguimentos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Imunoterapia/métodos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Masculino , Pessoa de Meia-Idade , Prognóstico , Taxa de SobrevidaRESUMO
BACKGROUND: Topical tretinoin cream is the gold standard treatment for skin ageing, particularly photoaging. The purpose of tretinoin peel was to obtain similar results, but in a shorter time, however, there have been few controlled trials on its effectiveness. OBJECTIVE: To compare efficacy and safety of tretinoin 0.05% cream and 5% as a peeling agent on photoaging and field cancerization of the forearms. METHODS: Clinical trial with therapeutic intervention, prospective, randomized (computer-generated randomization list), parallel, comparative (intrasubject) and evaluator-blinded (except for histology and immunohistochemistry), including 24 women (48 forearms) aged over 60 years who have not undergone hormone replacement and categorized as Fitzpatrick skin phototype II or III. The forearms of the participants were randomized for treatment with 0.05% tretinoin cream three nights a week, or 5% tretinoin peel every 2 weeks. The opinion of the participant, severity of photoaging, corneometry, profilometry, high-frequency ultrasound, histology (haematoxylin-eosin and Verhoeff stainings) and immunohistochemistry (p53, bcl-2, Ki67 and collagen I) were assessed. RESULTS: One participant dropped out. The mean photoaging score reduced 20% and the mean actinic keratosis (AK) count reduced 60% with no difference between treatments. Three efficacy parameters showed opposite effects between the tretinoin treatments (P < 0.05%): (i) thickness of the corneal layer decreased with 0.05% tretinoin and increased by 5%; (ii) dermis echogenicity increased by 0.05% and decreased by 5% and (iii) Ki67 expression increased by 0.05% and decreased by 5%. There was good tolerability for both regimens. CONCLUSION: Tretinoin as a cream 0.05% or peeling (5%) is safe and effective for the treatment of moderate photoaging and forearm field cancerization. The cream was superior in improving ultrasonographic parameters of ageing. Peeling was shown a superior performance in the stabilization of field cancerization.
Assuntos
Antineoplásicos/administração & dosagem , Abrasão Química , Ceratose Actínica/tratamento farmacológico , Envelhecimento da Pele/efeitos dos fármacos , Creme para a Pele/administração & dosagem , Tretinoína/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Derme/diagnóstico por imagem , Epiderme/diagnóstico por imagem , Feminino , Antebraço , Humanos , Ceratose Actínica/metabolismo , Ceratose Actínica/patologia , Antígeno Ki-67/metabolismo , Estudos Prospectivos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Método Simples-Cego , Envelhecimento da Pele/patologia , Creme para a Pele/efeitos adversos , Fenômenos Fisiológicos da Pele/efeitos dos fármacos , Tretinoína/efeitos adversos , Proteína Supressora de Tumor p53/metabolismo , UltrassonografiaRESUMO
Tap water from 497 properties using private water supplies, in an area of metalliferous and arsenic mineralisation (Cornwall, UK), was measured to assess the extent of compliance with chemical drinking water quality standards, and how this is influenced by householder water treatment decisions. The proportion of analyses exceeding water quality standards were high, with 65 % of tap water samples exceeding one or more chemical standards. The highest exceedances for health-based standards were nitrate (11 %) and arsenic (5 %). Arsenic had a maximum observed concentration of 440 µg/L. Exceedances were also high for pH (47 %), manganese (12 %) and aluminium (7 %), for which standards are set primarily on aesthetic grounds. However, the highest observed concentrations of manganese and aluminium also exceeded relevant health-based guidelines. Significant reductions in concentrations of aluminium, cadmium, copper, lead and/or nickel were found in tap waters where households were successfully treating low-pH groundwaters, and similar adventitious results were found for arsenic and nickel where treatment was installed for iron and/or manganese removal, and successful treatment specifically to decrease tap water arsenic concentrations was observed at two properties where it was installed. However, 31 % of samples where pH treatment was reported had pH < 6.5 (the minimum value in the drinking water regulations), suggesting widespread problems with system maintenance. Other examples of ineffectual treatment are seen in failed responses post-treatment, including for nitrate. This demonstrates that even where the tap waters are considered to be treated, they may still fail one or more drinking water quality standards. We find that the degree of drinking water standard exceedances warrant further work to understand environmental controls and the location of high concentrations. We also found that residents were more willing to accept drinking water with high metal (iron and manganese) concentrations than international guidelines assume. These findings point to the need for regulators to reinforce the guidance on drinking water quality standards to private water supply users, and the benefits to long-term health of complying with these, even in areas where treated mains water is widely available.
Assuntos
Água Potável/química , Purificação da Água/métodos , Arsênio/análise , Inglaterra , Monitoramento Ambiental , Água Subterrânea/análise , Concentração de Íons de Hidrogênio , Metais/análise , Nitratos/análise , Poluentes Químicos da Água/análise , Qualidade da Água/normas , Abastecimento de Água/métodosRESUMO
Influenza antigen detection assays (Sofia fluorescent immunoassay [FIA] and Veritor) yield objective results, which are potentially useful for point-of-care testing. The assays were evaluated with reverse transcriptase PCR (RT-PCR) using 411 nasopharyngeal swab specimens. Sensitivity and specificity values (percentages) of 79.0/99.0 and 64.0/99.4 for influenza A and 92.9/96.7 and 78.6/98.7 for influenza B were obtained for the Sofia and Veritor assays, respectively.
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Antígenos Virais/isolamento & purificação , Vírus da Influenza A/isolamento & purificação , Vírus da Influenza B/isolamento & purificação , Influenza Humana/diagnóstico , Influenza Humana/virologia , Nasofaringe/virologia , Humanos , Imunoensaio/métodos , Sistemas Automatizados de Assistência Junto ao Leito , Kit de Reagentes para Diagnóstico/virologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Sensibilidade e EspecificidadeAssuntos
Protetores Solares , Raios Ultravioleta , Humanos , Pele , Raios Ultravioleta/efeitos adversosRESUMO
BACKGROUND AND OBJECTIVE: Myofascial pain syndrome (MPS) is a chronic musculoskeletal disorder characterized by the presence of trigger points. Among the treatment options, botulinum toxin injections have been investigated. The aim of this paper was to provide a synthesis of the evidence on intramuscular botulinum toxin injections for upper back MPS. DATABASES AND DATA TREATMENT: A systematic review of the literature was performed on the PubMed, Scopus and Cochrane Library, using the following formula: ("botulinum") AND ("musculoskeletal") AND ("upper back pain") OR ("myofascial pain"). RESULTS: Ten studies involving 651 patients were included. Patients in the control groups received placebo (saline solution) injections, anaesthetic injections + dry needling or anaesthetic injections. The analysis of the trials revealed modest methodological quality: one "Good quality" study, one "Fair" and the other "Poor". No major complications or serious adverse events were reported. Results provided conflicting evidence and did not demonstrate the superiority of botulinum toxin over comparators. Most of the included trials were characterized by a small sample size, weak power analysis, different clinical scores used and non-comparable follow-up periods. Even if there is no conclusive evidence, the favourable safety profile and the positive results of some secondary endpoints suggest a potentially beneficial action in pain control and quality of life. CONCLUSION: The currently available studies show conflicting results. Their overall low methodological quality does not allow for solid evidence of superiority over other comparison treatments. Further insights are needed to properly profile patients who could benefit more from this peculiar injective approach. SIGNIFICANCE: The randomized controlled trials included in this review compared using botulinum toxin to treat upper back MPS with placebo or active treatments (e.g., dry needling or anaesthetics) showing mixed results overall. Despite the lack of clear evidence of superiority, our study suggests that the use of botulinum toxin should not be discouraged. Its safety profile and encouraging results in pain control, motor recovery and disability reduction make it an interesting treatment, particularly in the subset of patients with moderate to severe chronic pain and active trigger points. To support the safety and efficacy of botulinum toxin, further high-quality studies are needed.
Assuntos
Anestésicos , Toxinas Botulínicas Tipo A , Fibromialgia , Síndromes da Dor Miofascial , Humanos , Toxinas Botulínicas Tipo A/uso terapêutico , Toxinas Botulínicas Tipo A/efeitos adversos , Injeções Intramusculares , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Síndromes da Dor Miofascial/tratamento farmacológico , Fibromialgia/tratamento farmacológico , Dor nas Costas , Anestésicos/uso terapêuticoRESUMO
Objective: In this study a multi fragment humeral fracture, treated with locking plate system implant, was investigate and compared with a healthy humerus by the mining of a Finite Element (FE) analysis. Locking plate implant, in this case AxSOS 3® Titanium produced by Stryker is the preferred solution in presence of multiple fracture or osteoporosis. Methods: Loading conditions were imposed by rotating of 52,5° respect the vertical axe, both the humeri (healthy and fractured), fixing distal end, and loading the top of bones with a vertical force of 543 N (Newton). This finite element analysis aimed to compare stability of implanted humerus, implant-bone interface, stress shielding, with those related to a healthy one. A microbial adhesion analysis was also performed on the implant's material. Results: Results obtained by FE analysis confirm a good agreement of the mechanical behavior of the models tested. The maximum values of the registered stressed, are of about 45 MPa (Mega Pascal) for the intact humerus and 113 MPa for the fractured one. Displacements, confirm higher values on the fractured humerus and no viable bacteria were found after microbial adhesion analyses.Conclusion: comparison between healthy and fractured humerus showed an optimal stability of the implant, when contact surfaces optimization and screws insertion are correctly performed.
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OBJECTIVES: Carbon monoxide (CO) poisoning represents a significant public health burden. CO incidents require multiple responders, including the Health Protection Agency (HPA). However, best practice guidance does not yet exist in the UK for chemicals. Since CO is a good template for chemical incidents, the authors aimed to develop an electronic 'best practice' CO incident response toolkit which could serve as a blueprint for chemicals in general, and have compatibility with HPZone, the electronic decision support system being implemented across the HPA. STUDY DESIGN: Public health guidance development. METHODS: (1) Literature review of CO incidents, risk management, public health, toxicology and environmental guidance; (2) expert opinion; (3) synthesis of information; (4) writing the toolkit; and (5) consultation and toolkit testing. RESULTS: The draft toolkit was designed integrating a best practice algorithm, risk assessment, links to CO guidance, and template incident forms. The risk assessment model is in development but key intermediate outcomes of this were proposed case definitions for CO exposure. CONCLUSION: The toolkit has been successfully piloted and further consultation and refinement will follow. It provides a platform for the expansion of electronic decision support tools in chemical incidents management with the potential for HPZone functionality.
Assuntos
Benchmarking/métodos , Intoxicação por Monóxido de Carbono/terapia , Serviços Médicos de Emergência/métodos , Exposição Ocupacional , Saúde Pública/métodos , Algoritmos , Intoxicação por Monóxido de Carbono/diagnóstico , Sistemas de Apoio a Decisões Clínicas , Exposição Ambiental , Fidelidade a Diretrizes , Humanos , Saúde Ocupacional , Medição de Risco/métodosRESUMO
OBJECTIVE: The aim of the study was to review the available literature on the application of oxygen-ozone therapy (OOT) in the treatment of low back pain (LBP), to understand its therapeutic potential and compare it with other available treatment options. MATERIALS AND METHODS: A systematic review was performed on the PubMed and Scopus databases, with the following inclusion criteria: (1) randomized controlled trials (RCTs), (2) published in the last 20 years, (3) dealing with OOT in patients with LBP and herniated disc, (4) comparing the results of OOT with those of other treatments. The risk of bias was assessed by the Cochrane Risk of Bias tool. RESULTS: Fifteen studies involving 2597 patients in total were included. Patients in the control groups received different treatments, from oral drugs to other injections, instrumental therapy and even surgery: corticosteroids were used in 5 studies, analgesic therapy in 2 studies; placebo, microdiscectomy, laser-therapy, TENS and postural rehabilitation, percutaneous radiofrequency intradiscal thermocoagulation and psoas compartmental block were tested in the other trials. Looking at the quality of the literature, none of the studies included reached "good quality" standard, 3 were ranked as "fair" and the rest were considered "poor". Comparison of OOT results with other approaches showed that, in the majority of studies, OOT was superior to the control treatment, and also when compared to microdiscectomy, ozone showed non inferiority in terms of clinical outcomes. CONCLUSIONS: The analysis of literature revealed overall poor methodologic quality, with most studies flawed by relevant bias. However, OOT has proven to be a safe treatment with beneficial effects in pain control and functional recovery at short to medium term follow-up.
Assuntos
Dor Lombar/terapia , Oxigênio/administração & dosagem , Ozônio/administração & dosagem , Viés , Humanos , Deslocamento do Disco Intervertebral/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do TratamentoRESUMO
OBJECTIVE: At present, several strategies for preventing neuromuscular pain in Type 2 Diabetes Mellitus (T2DM) have been investigated. Recently, findings on genetic variants associated with adverse events to statin-based therapy have been reported. The study aimed at measuring whether Pharmacogenomics (PGx) profile can affect neuromuscular pain in patients carrying T2DM and cardiovascular diseases. An extensive panel of 5 polymorphisms on 4 candidate genes, previously validated as significant markers related to Sulphonylureas and Glitinides (SU-G) plus Simvastatin neuromuscular toxicity, is herein analyzed and discussed. PATIENTS AND METHODS: We genotyped 76 T2DM patients carrying cardiovascular dyscrasia undergone anti-diabetic and anti-cholesterolemic polypharmacy. 35 subjects out of the total received concurrent SU-G and Statin-based therapy. Candidate variants consisted of drug transporters, such as Solute Carrier Organic 1B1 (SLCO1B1) Val174Ala ATP-binding cassette subfamily B member (ABCB1), subfamily C member 8 (ABCC8), and drug biotransformers of Cytochrome P450 Family (CYP) including CYP2C9*2 CYP2C9*3 CYP2C8*3, and CYP3A4*22. Moreover, we also focused on an early outline evaluation of the genotyping costs and benefits. RESULTS: 6 out of 35 patients treated with SU-G plus statins (17.1% experienced adverse neuropathy events). Pharmacogenomics analysis showed a lack of any correlation between candidate gene polymorphisms and toxicity, except for the SLCO1B1 T521C allele; 14.3% of patients had a high risk for grade >2 neuromuscular pain (Odds Ratio [OR] 2.61.95% CI 0.90-7.61, p=0.03). CONCLUSIONS: The clinical polymorphism effectiveness outlined therein will be assured by diagnostic improvements suitable for driving treatment decisions. In light of our experimental results and literature data, the analysis of the SLCO1B1 T521C variant will allow clinicians to take advantage from a better treatment planned for their patients in order to minimize neuromuscular pain and maximize benefits.
Assuntos
Doenças Cardiovasculares/genética , Diabetes Mellitus Tipo 2/genética , Transportador 1 de Ânion Orgânico Específico do Fígado/genética , Dor/genética , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/tratamento farmacológico , DNA/genética , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Genótipo , Humanos , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/uso terapêutico , Masculino , Pessoa de Meia-Idade , Dor/diagnóstico , Dor/tratamento farmacológico , Medição da Dor , Farmacogenética , Polimorfismo de Nucleotídeo Único/genética , Sinvastatina/efeitos adversos , Sinvastatina/uso terapêutico , Compostos de Sulfonilureia/efeitos adversos , Compostos de Sulfonilureia/uso terapêuticoRESUMO
Cardiac screening is recommended to prevent cardiovascular death after renal transplantation. This retrospective observational study illustrates the results of application of a cardiac assessment algorithm in a series of 558 renal transplant candidates at a single center in Turin, Italy. A dipyridamole-stress sestamibi myocardial scintiscan (DMS) performed in 302/558 (54.1%) cases was positive in 52 (17.2%), negative in 200 (66.2%), borderline in 16 (5.3%), and with signs of previous necrosis in 34 (11.4%). Coronary lesions detected by angiography in 48.1% of the 52 positives were treated medically (13.5%) or by percutaneous/surgical procedure (34.6%). Coronary lesions were detected in 14.1% of asymptomatic population subgroup. The minor and major cardiovascular event rates and the cardiovascular death rate were 1.9%, 0%, and 0%, respectively, in positive DMS group (high-cardiological risk) vs. 10%, 4.5%, and 3.5% in the negatives (p > 0.5; n.s.). It is suggested that not increased cardiovascular event or deaths rates in the high-risk group reflect early coronary lesion detection and correction. Since 55.9% of cardiovascular events or deaths occurred in the negative group more than 24 months after the DMS, its mandatory repetition every two yr after a negative finding is recommended.
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Doenças Cardiovasculares/etiologia , Falência Renal Crônica/cirurgia , Transplante de Rim , Listas de Espera , Adulto , Idoso , Algoritmos , Doenças Cardiovasculares/fisiopatologia , Dipiridamol , Teste de Esforço , Feminino , Humanos , Itália , Falência Renal Crônica/complicações , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Resultado do TratamentoRESUMO
Cosmetics, personal care and biomedical products obtained by bio-based polymers and natural bioactive compounds are a new growing market. The ecological awareness is changing consumers' demands, causing consumers to look for more sustainable options, with a reduced environmental impact. The innovation of this work was to develop a natural polymer matrix (chitosan) entrapping antioxidant actives compounds such as annatto (Bixa Orellana L.) and vitamin C with potential application as sustainable anti-aging skin mask treatment. Films of chitosan (Ch) and reacetylated chitosan (RCh), exhibiting different degrees of acetylation (DAâ¯=â¯13.3 and 33.9%, respectively), were produced. The formulations of active films of chitosan (BCh) and reacetylated chitosan (BRCh) were 1% (w/w) of chitosan, 1% (w/w) of annatto powder, 5% (w/w) of vitamin C and 1% (w/w) of glycerol (as plasticizer). Reacetylated chitosan films (DAâ¯=â¯33.9%) presented higher water affinity than chitosan films (DAâ¯=â¯13.3%). The elongation of RCh and BRCh increased and the resistance decreased, as compared to Ch and BCh. The antioxidants compounds (annatto and vitamin C) of BRCh films released faster than BCh films. Thus, the BRCh films showed potential application as an anti-aging skin mask.
Assuntos
Envelhecimento/efeitos dos fármacos , Antioxidantes/química , Antioxidantes/farmacologia , Quitosana/química , Cosméticos/química , Portadores de Fármacos/química , Pele/efeitos dos fármacos , Ácido Ascórbico/química , Ácido Ascórbico/farmacologia , Bixaceae/química , Carotenoides/química , Carotenoides/farmacologia , Linhagem Celular , Quitosana/metabolismo , Cor , Portadores de Fármacos/metabolismo , Humanos , Fenômenos Mecânicos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Solubilidade , VaporRESUMO
Dust elemental levels can be expressed as concentrations (bulk samples) or surface loadings (wipe samples). Wipe sampling has not been widely adopted for elements other than lead (Pb). In this study, 433 wipe samples from 130 households in south west England - a region of widespread, natural and anthropogenic arsenic contamination linked with previous mining activities-were analysed to (i) quantify loadings of arsenic (As); (ii) assess the quality of wipe data using QA/QC criteria; (iii) estimate, using published ingestion rates, human exposure to As in dust using loadings and concentrations from 97 bulk samples and (iv) comparatively assess the performance of wipe and bulk sampling using associations with As biomonitoring data (urine, toenails and hair). Good QC performance was observed for wipes: strong agreement between field duplicates, non-detectable contamination of field blank wipes and good reference material recoveries. Arsenic loadings exceeded an existing urban background benchmark in 67 (52%) households. No exceedances of tolerable daily As intake were observed for adult exposure estimates but infant estimates exceeded for 1 household. Infant estimates calculated using bulk concentrations resulted in 4 (3%) exceedances. Neither wipe nor bulk As metrics were sufficiently better predictors of As in biospecimens. Sampling strategies, analytical protocols, exposure metrics and assessment criteria require refinement to validate dust sampling methodologies.
Assuntos
Poluição do Ar em Ambientes Fechados/análise , Arsênio/análise , Poeira/análise , Exposição Ambiental/análise , Monitoramento Ambiental/métodos , Mineração , Inglaterra , HumanosRESUMO
Periventricular heterotopia (PH) occurs when collections of neurons lay along the lateral ventricles or just beneath. Human Filamin A gene (FLNA) mutations are associated with classical X-linked bilateral periventricular nodular heterotopia (PNH), featuring contiguous heterotopic nodules, mega cisterna magna, cardiovascular malformations and epilepsy. FLNA encodes an F-actin-binding cytoplasmic phosphoprotein and is involved in early brain neurogenesis and neuronal migration. A rare, recessive form of bilateral PNH with microcephaly and severe delay is associated with mutations of the ADP-ribosylation factor guanine nucleotide-exchange factor-2 (ARFGEF2) gene, required for vesicle and membrane trafficking from the trans-Golgi. However, PH is a heterogeneous disorder. We studied clinical and brain MRI of 182 patients with PH and, based on its anatomic distribution and associated birth defects, identified 15 subtypes. Classical bilateral PNH represented the largest group (98 patients: 54%). The 14 additional phenotypes (84 patients: 46%) included PNH with Ehlers-Danlos syndrome (EDS), temporo-occipital PNH with hippocampal malformation and cerebellar hypoplasia, PNH with fronto-perisylvian or temporo-occipital polymicrogyria, posterior PNH with hydrocephalus, PNH with microcephaly, PNH with frontonasal dysplasia, PNH with limb abnormalities, PNH with fragile-X syndrome, PNH with ambiguous genitalia, micronodular PH, unilateral PNH, laminar ribbon-like and linear PH. We performed mutation analysis of FLNA in 120 patients, of whom 72 (60%) had classical bilateral PNH and 48 (40%) other PH phenotypes, and identified 25 mutations in 40 individuals. Sixteen mutations had not been reported previously. Mutations were found in 35 patients with classical bilateral PNH, in three with PNH with EDS and in two with unilateral PNH. Twenty one mutations were nonsense and frame-shift and four missense. The high prevalence of mutations causing protein truncations confirms that loss of function is the major cause of the disorder. FLNA mutations were found in 100% of familial cases with X-linked PNH (10 families: 8 with classical bilateral PNH, 1 with EDS and 1 with unilateral PH) and in 26% of sporadic patients with classical bilateral PNH. Overall, mutations occurred in 49% of individuals with classical bilateral PNH irrespective of their being familial or sporadic. However, the chances of finding a mutation were exceedingly gender biased with 93% of mutations occurring in females and 7% in males. The probability of finding FLNA mutations in other phenotypes was 4% but was limited to the minor variants of PNH with EDS and unilateral PNH. Statistical analysis considering all 42 mutations described so far identifies a hotspot region for PNH in the actin-binding domain (P < 0.05).
Assuntos
Encéfalo/anormalidades , Proteínas Contráteis/genética , Doenças Genéticas Ligadas ao Cromossomo X/genética , Proteínas dos Microfilamentos/genética , Mutação , Anormalidades Múltiplas/genética , Adolescente , Adulto , Criança , Pré-Escolar , Síndrome de Ehlers-Danlos/genética , Feminino , Filaminas , Síndrome do Cromossomo X Frágil/genética , Genótipo , Humanos , Hidrocefalia/genética , Deformidades Congênitas dos Membros/genética , Imageamento por Ressonância Magnética/métodos , Masculino , Microcefalia/genética , Pessoa de Meia-Idade , Linhagem , FenótipoRESUMO
OBJECTIVES: To investigate the effects of high ambient temperatures, including the summer 2003 heat-episode, on NHS Direct usage and its suitability as a surveillance tool in heat health warning systems. METHODS: Analyses of data on calls to NHS Direct in English Regions in the period Dec 2001-May 2004. Outcomes were daily rates of all symptomatic calls, and daily proportion of calls for selected causes (fever, vomiting, difficulty breathing, heat/sun-stroke) RESULTS: Total calls were moderately increased as environmental temperature increased; this effect was greatest in calls for young children and for fever. Total calls were moderately elevated during two summer heat episodes in 2003: calls specifically for heat/sun stroke increased acutely in response to these episodes. No association was apparent between environmental temperature and proportion of calls for vomiting and difficulty breathing. CONCLUSIONS: Calls to NHS Direct are sensitive to daily temperatures and extreme weather. NHS Direct is timely and has great potential in health surveillance. Calls for heat- and sun-stroke are now routinely monitored as part of the UK Heat-wave plan
Assuntos
Temperatura Alta/efeitos adversos , Vigilância da População , Medicina Estatal/estatística & dados numéricos , Adolescente , Adulto , Fatores Etários , Idoso , Criança , Pré-Escolar , Estudos Transversais , Dispneia/epidemiologia , Inglaterra , Febre/epidemiologia , Golpe de Calor/epidemiologia , Humanos , Lactente , Londres , Pessoa de Meia-Idade , Insolação/epidemiologia , Temperatura , Vômito/epidemiologiaRESUMO
Chronic exposure to arsenic (As) in drinking water is an established cause of cancer and other adverse health effects. Arsenic concentrations >10 µg L(-1) were previously measured in 5% of private water supplies (PWS) in Cornwall, UK. The present study investigated prolongued exposure to As by measuring biomarkers in hair and toenail samples from 212 volunteers and repeated measurements of As in drinking water from 127 households served by PWS. Strong positive Pearson correlations (rp = 0.95) indicated stability of water As concentrations over the time period investigated (up to 31 months). Drinking water As concentrations were positively correlated with toenail (rp = 0.53) and hair (rp = 0.38) As concentrations - indicative of prolonged exposure. Analysis of washing procedure solutions provided strong evidence of the effective removal of exogenous As from toenail samples. Significantly higher As concentrations were measured in hair samples from males and smokers and As concentrations in toenails were negatively associated with age. A positive association between seafood consumption and toenail As and a negative association between home-grown vegetable consumption and hair As was observed for volunteers exposed to <1 As µg L(-1) in drinking water. These findings have important implications regarding the interpretation of toenail and hair biomarkers. Substantial variation in biomarker As concentrations remained unaccounted for, with soil and dust exposure as possible explanations.
Assuntos
Arsênio/análise , Biomarcadores/análise , Água Potável/análise , Exposição Ambiental/análise , Cabelo/química , Unhas/química , Poluentes Químicos da Água/análise , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores Sexuais , Reino Unido , Abastecimento de Água , Adulto JovemRESUMO
Private water supplies (PWS) in Cornwall, South West England exceeded the current WHO guidance value and UK prescribed concentration or value (PCV) for arsenic of 10 µg/L in 5% of properties surveyed (n = 497). In this follow-up study, the first of its kind in the UK, volunteers (n = 207) from 127 households who used their PWS for drinking, provided urine and drinking water samples for total As determination by inductively coupled plasma mass spectrometry (ICP-MS) and urinary As speciation by high performance liquid chromatography ICP-MS (HPLC-ICP-MS). Arsenic concentrations exceeding 10 µg/L were found in the PWS of 10% of the volunteers. Unadjusted total urinary As concentrations were poorly correlated (Spearman's ρ = 0.36 (P < 0.001)) with PWS As largely due to the use of spot urine samples and the dominance of arsenobetaine (AB) from seafood sources. However, the osmolality adjusted sum, U-As(IMM), of urinary inorganic As species, arsenite (As(III)) and arsenate (As(V)), and their metabolites, methylarsonate (MA) and dimethylarsinate (DMA), was found to strongly correlate (Spearman's ρ: 0.62 (P < 0.001)) with PWS As, indicating private water supplies as the dominant source of inorganic As exposure in the study population of PWS users.
Assuntos
Arsênio/urina , Água Potável/análise , Exposição Ambiental/análise , Abastecimento de Água , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Demografia , Características da Família , Feminino , Geografia , Humanos , Masculino , Pessoa de Meia-Idade , Reino Unido , Adulto JovemRESUMO
INTRODUCTION: Worldwide organ shortage and the increasing age of end-stage renal disease patients demanding a graft have prompted extensive use of marginal donors. The "old-for-old" allocation has been proposed for the elderly. The aim of this study was to evaluate the results of a policy of free acceptance into the waiting list of recipients older than 65 years. METHODS: From 1987 to 2004 70 patients whose mean age was 67.4 +/- 2.8 years, underwent an extensive pretransplant evaluation including cardiac studies. Immunosuppression was based upon low-dose steroids, and cyclosporine (50%) or tacrolimus (44%). RESULTS: Patient and graft survival at 1, 3, 5, and 10 years were 85%, 78.5%, 75%, 50%, and 80%, 74%, 70%, 36%, respectively. Death occurred in 17/70 (24%), 14 of whom had a functioning graft. The causes of death were 30% cancer, 23% cardiovascular, 23% sepsis, 12% cerebrovascular hemorrhage, 12% meningitis. The acute rejection (AR) rate was 18.6%. The causes of graft loss were: 71% patient death, 4% irreversible AR, 4% vascular thrombosis, and 21% chronic allograft dysfunction. The main complications were: 52% prostatic hypertrophy, 40% urinary tract infections, 8.6% diabetes, 11% pneumonia, 10% cardiovascular diseases, 7% urological complications, 8% abdominal pathology, 6% acute pyelonephritis, 8% non-skin cancer. CONCLUSIONS: Despite the increased vulnerability of the elderly, they should not be excluded a priori from renal transplantation. Extensive pretransplant screening, mainly cardiovascular, and a tailored immunosuppression are two crucial issues. The moderate rate of AR suggests that these patients do not have an impaired immunocompetence as far as acute rejection is concerned.