RESUMO
Magnetic Johnson noise is an important consideration for many applications involving precision magnetometry, and its significance will only increase in the future with improvements in measurement sensitivity. The fluctuation-dissipation theorem can be utilized to derive analytic expressions for magnetic Johnson noise in certain situations. But when used in conjunction with commercially available finite element analysis tools, the combined approach is particularly powerful as it provides a practical means to calculate the magnetic Johnson noise arising from conductors of arbitrary geometry and permeability. In this paper, we demonstrate this method to be one of the most comprehensive approaches presently available to calculate thermal magnetic noise. In particular, its applicability is shown to not be limited to cases where the noise is evaluated at a point in space but also can be expanded to include cases where the magnetic field detector has a more general shape, such as a finite size loop, a gradiometer, or a detector that consists of a polarized atomic species trapped in a volume. Furthermore, some physics insights gained through studies made using this method are discussed.
RESUMO
Manganese hydroxido (Mn-OH) complexes supported by a tripodal N,N',Nâ³-[nitrilotris(ethane-2,1-diyl)]tris(P,P-diphenylphosphinic amido) ([poat]3-) ligand have been synthesized and characterized by spectroscopic techniques including UV-vis and electron paramagnetic resonance (EPR) spectroscopies. X-ray diffraction (XRD) methods were used to confirm the solid-state molecular structures of {Na2[MnIIpoat(OH)]}2 and {Na[MnIIIpoat(OH)]}2 as clusters that are linked by the electrostatic interactions between the sodium counterions and the oxygen atom of the ligated hydroxido unit and the phosphinic (P=O) amide groups of [poat]3-. Both clusters feature two independent monoanionic fragments in which each contains a trigonal bipyramidal Mn center that is comprised of three equatorial deprotonated amide nitrogen atoms, an apical tertiary amine, and an axial hydroxido ligand. XRD analyses of {Na[MnIIIpoat(OH)]}2 also showed an intramolecular hydrogen bonding interaction between the MnIII-OH unit and P=O group of [poat]3-. Crystalline {Na[MnIIIpoat(OH)]}2 remains as clusters with Na+---O interactions in solution and is unreactive toward external substrates. However, conductivity studies indicated that [MnIIIpoat(OH)]- generated in situ is monomeric and reactivity studies found that it is capable of cleaving C-H bonds, illustrating the importance of solution-phase speciation and its direct effect on chemical reactivity. Synopsis: Manganese-hydroxido complexes were synthesized to study the influence of H-bonds in the secondary coordination sphere and their effects on the oxidative cleavage of substrates containing C-H bonds.
Assuntos
Complexos de Coordenação , Manganês , Manganês/química , Complexos de Coordenação/química , Complexos de Coordenação/síntese química , Lipoxigenase/química , Lipoxigenase/metabolismo , Espectroscopia de Ressonância de Spin Eletrônica , Materiais Biomiméticos/química , Materiais Biomiméticos/síntese químicaRESUMO
Transient molecules in the gastrointestinal tract such as nitric oxide and hydrogen sulfide are key signals and mediators of inflammation. Owing to their highly reactive nature and extremely short lifetime in the body, these molecules are difficult to detect. Here we develop a miniaturized device that integrates genetically engineered probiotic biosensors with a custom-designed photodetector and readout chip to track these molecules in the gastrointestinal tract. Leveraging the molecular specificity of living sensors1, we genetically encoded bacteria to respond to inflammation-associated molecules by producing luminescence. Low-power electronic readout circuits2 integrated into the device convert the light emitted by the encapsulated bacteria to a wireless signal. We demonstrate in vivo biosensor monitoring in the gastrointestinal tract of small and large animal models and the integration of all components into a sub-1.4 cm3 form factor that is compatible with ingestion and capable of supporting wireless communication. With this device, diseases such as inflammatory bowel disease could be diagnosed earlier than is currently possible, and disease progression could be more accurately tracked. The wireless detection of short-lived, disease-associated molecules with our device could also support timely communication between patients and caregivers, as well as remote personalized care.
Assuntos
Biomarcadores , Técnicas Biossensoriais , Sulfeto de Hidrogênio , Inflamação , Óxido Nítrico , Animais , Biomarcadores/análise , Biomarcadores/metabolismo , Técnicas Biossensoriais/instrumentação , Técnicas Biossensoriais/métodos , Doenças Inflamatórias Intestinais/diagnóstico , Doenças Inflamatórias Intestinais/metabolismo , Modelos Animais , Trato Gastrointestinal/metabolismo , Trato Gastrointestinal/microbiologia , Cápsulas/administração & dosagem , Probióticos/metabolismo , Bactérias/metabolismo , Luminescência , Progressão da Doença , Inflamação/diagnóstico , Inflamação/metabolismo , Óxido Nítrico/análise , Óxido Nítrico/metabolismo , Sulfeto de Hidrogênio/análise , Sulfeto de Hidrogênio/metabolismo , Tecnologia sem Fio/instrumentação , Administração Oral , Tecnologia de Sensoriamento Remoto/instrumentação , Tecnologia de Sensoriamento Remoto/métodos , Fatores de Tempo , Humanos , Tamanho CorporalRESUMO
INTRODUCTION: Alzheimer's disease (AD) is a disease continuum from pathophysiologic, biomarker and clinical perspectives. With the advent of advanced technologies, diagnosing and managing patients is evolving. METHODS: A systematic literature review (SLR) of practice guidelines for mild cognitive impairment (MCI) and AD dementia was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). This systematic literature review (SLR) aimed to summarize current clinical practice guidelines for screening, testing, diagnosis, treatment and monitoring in the AD continuum. The results of this SLR were used to propose a way forward for practice guidelines given the possible introduction of biomarker-guided technology using blood- or plasma-based assays and disease-modifying treatments (DMTs) targeted for early disease. RESULTS: 53 clinical practice guidelines were identified, 15 of which were published since 2018. Screening for asymptomatic populations was not recommended. Biomarker testing was not included in routine diagnostic practice. There was no consensus on which neurocognitive tests to use to diagnose and monitor MCI or AD dementia. Pharmacologic therapies were not recommended for MCI, while cholinesterase inhibitors and memantine were recommended for AD treatment. DISCUSSION: The pre-2018 and post-2018 practice guidelines share similar recommendations for screening, diagnosis and treatment. However, once DMTs are approved, clinicians will require guidance on the appropriate use of DMTs in a clinical setting. This guidance should include strategies for identifying eligible patients and evaluating the DMT benefit-to-risk profile to facilitate shared decision-making among physicians, patients and care partners. CONCLUSION: Regular evidence-based updates of existing guidelines for the AD continuum are required over the coming decades to integrate rapidly evolving technologic and medical scientific advances and bring emerging approaches for management of early disease into clinical practice. This will pave the way toward biomarker-guided identification and targeted treatment and the realization of precision medicine for AD.
RESUMO
A series of ß-diketiminate Ni-NO complexes with a range of NO binding modes and oxidation states were studied by X-ray emission spectroscopy (XES). The results demonstrate that XES can directly probe and distinguish end-on vs side-on NO coordination modes as well as one-electron NO reduction. Density functional theory (DFT) calculations show that the transition from the NO 2s2s σ* orbital has higher intensity for end-on NO coordination than for side-on NO coordination, whereas the 2s2s σ orbital has lower intensity. XES calculations in which the Ni-N-O bond angle was fixed over the range from 80° to 176° suggest that differences in NO coordination angles of â¼10° could be experimentally distinguished. Calculations of Cu nitrite reductase (NiR) demonstrate the utility of XES for characterizing NO intermediates in metalloenzymes. This work shows the capability of XES to distinguish NO coordination modes and oxidation states at Ni and highlights applications in quantifying small molecule activation in enzymes.
RESUMO
Hot isostatic pressing (HIP) is often needed to obtain powder bed fused (PBF) Ti-6Al-4V parts with good fatigue performance. This manuscript attempts to clarify the mechanisms through which HIP treatment acts to improve high cycle fatigue performance. Several mechanisms are considered and examined against experimental data sets available in the literature. The results suggest that HIP may act most significantly by decreasing the fraction of the defect population that can initiate fatigue cracks, both by decreasing defect sizes below a threshold and by changing the microstructure that surrounds defects. Given the novelty of the latter conclusion, an electron backscatter diffraction microscopy study was performed for validation. The gained understanding provides initial guidance on the choice of optimum HIP soak parameters (Temperature-Pressure-Time) for the high cycle fatigue performance of PBF Ti-6Al-4V.
RESUMO
Linkage isomers of reduced metal-nitrosyl complexes serve as key species in nitric oxide (NO) reduction at monometallic sites to produce nitrous oxide (N2O), a potent greenhouse gas. While factors leading to extremely rare side-on nitrosyls are unclear, we describe a pair of nickel-nitrosyl linkage isomers through controlled tuning of noncovalent interactions between the nitrosyl ligands and differently encapsulated potassium cations. Furthermore, these reduced metal-nitrosyl species with N-centered spin density undergo radical coupling with free NO and provide a N-N coupled cis-hyponitrite intermediate whose protonation triggers the release of N2O. This report outlines a stepwise molecular mechanism of NO reduction to form N2O at a mononuclear metal site that provides insight into the related biological reduction of NO to N2O.
Assuntos
Óxido Nítrico/química , Óxido Nitroso/química , Modelos Moleculares , Conformação Molecular , Nitritos/química , EstereoisomerismoRESUMO
BACKGROUND: Chronic rhinosinusitis is characterised by persistent inflammation of the sinonasal mucosa. Multiple pathophysiological mechanisms are likely to exist. Previous research has focused predominantly on T-helper type cytokines to highlight the inflammatory mechanisms. However, proteins such as nuclear factor kappa B and transforming growth factor beta are increasingly recognised to have important roles in sinonasal inflammation and tissue remodelling. OBJECTIVE: This review article explores the roles of T-helper type cytokines, nuclear factor kappa B and transforming growth factor beta in the pathophysiological mechanisms of chronic rhinosinusitis. An understanding of these mechanisms will allow for better identification and classification of chronic rhinosinusitis endotypes, and, ultimately, improved therapeutic strategies.
Assuntos
Citocinas/metabolismo , NF-kappa B/metabolismo , Rinite/imunologia , Sinusite/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Fator de Crescimento Transformador beta/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Doença Crônica , Citocinas/antagonistas & inibidores , Citocinas/imunologia , Humanos , NF-kappa B/antagonistas & inibidores , NF-kappa B/imunologia , Rinite/tratamento farmacológico , Rinite/metabolismo , Rinite/patologia , Sinusite/tratamento farmacológico , Sinusite/metabolismo , Sinusite/patologia , Fator de Crescimento Transformador beta/imunologiaRESUMO
BACKGROUND: Nephrogenic pruritus (NP) is a well-known associated symptom in patients with chronic renal failure. The aim of the present study was to make a detailed dermatological analysis including distribution of excoriations and their correlation with pruritus characteristics. PATIENTS AND METHODS: Data on a total of 17 patients with NP (14 males, mean 65.4 ± SD 14.3 years) were subjected to retrospective analysis. Most of the patients developed NP after start of kidney disease; however, in 20 % of the patients, there was premonitory appearance of the symptom 18 months (median) earlier. A majority of patients reported neuropathic symptom qualities (burning, stinging). In 94.1 % of patients xerosis was present; in 58.8 %, prurigo nodularis. The latter group of patients had a longer duration of pruritus as well as up to 10 years longer duration of renal disease than those without prurigo. RESULTS: Pruritus characteristics of NP show a wide variance without a clear profile that is useful for clinical diagnosis. NP can occur premonitorily, and, if of long duration and with coexistent metabolic diseases, can develop into prurigo.
Assuntos
Prurigo/etiologia , Prurido/diagnóstico , Prurido/etiologia , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/diagnóstico , Idoso , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Neuralgia/diagnóstico , Neuralgia/etiologiaRESUMO
Caffeoylquinic acids are found in artichokes, and they are currently considered important therapeutic or preventive agents for treating Alzheimer's disease and diabetes. We transformed artichoke [the cultivated cardoon or Cynara cardunculus var. altilis DC (Asteraceae)] with the rolC gene, which is a known inducer of secondary metabolism. High-performance liquid chromatography with UV and high-resolution mass spectrometry (HPLC-UV-HRMS) revealed that the predominant metabolites synthesized in the transgenic calli were 1,5-dicaffeoylquinic acid, 3,4-dicaffeoylquinic acid, and chlorogenic acid. The rolC-transformed calli contained 1.5% caffeoylquinic acids by dry weight. The overall production of these metabolites was three times higher than that of the corresponding control calli. The enhancing effect of rolC remained stable over long-term cultivation.
Assuntos
Cynara scolymus/metabolismo , Ácido Quínico/análogos & derivados , Cinamatos/metabolismo , Cynara scolymus/citologia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Ácido Quínico/metabolismoRESUMO
BACKGROUND: There are only a few studies about the body concept of patients with chronic pruritus. We examined the body concept of this group of patients taking into account subgroup-specific differences, limitations of quality of life and the comparison to patients with eating disorders and a healthy control group. METHODS: 284 participants with chronic pruritus filled in the Frankfurt Body Concept Scale, the Hospital Anxiety and Depression Scale and the Dermatology Life Quality Index. Statistical analysis was performed using t tests, variance analysis and Pearson's correlations. RESULTS: Patients with chronic pruritus had a more negative body concept than healthy individuals but a less negative concept than patients with eating disorders. Higher levels of depression and anxiety were related to a more negative body image. CONCLUSION: The body concept of patients with chronic pruritus should be taken into consideration when planning therapy. Whether the body concept changes after successful treatment has to be examined in further studies.
Assuntos
Ansiedade/psicologia , Imagem Corporal/psicologia , Depressão/psicologia , Prurido/psicologia , Adulto , Idoso , Estudos de Casos e Controles , Doença Crônica , Estudos Transversais , Transtornos da Alimentação e da Ingestão de Alimentos/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prurido/complicações , Escalas de Graduação Psiquiátrica , Qualidade de Vida/psicologia , Índice de Gravidade de Doença , Pele/lesões , Adulto JovemRESUMO
Tourette's syndrome (TS) is a developmental disorder that has one of the highest familial recurrence rates among neuropsychiatric diseases with complex inheritance. However, the identification of definitive TS susceptibility genes remains elusive. Here, we report the first genome-wide association study (GWAS) of TS in 1285 cases and 4964 ancestry-matched controls of European ancestry, including two European-derived population isolates, Ashkenazi Jews from North America and Israel and French Canadians from Quebec, Canada. In a primary meta-analysis of GWAS data from these European ancestry samples, no markers achieved a genome-wide threshold of significance (P<5 × 10(-8)); the top signal was found in rs7868992 on chromosome 9q32 within COL27A1 (P=1.85 × 10(-6)). A secondary analysis including an additional 211 cases and 285 controls from two closely related Latin American population isolates from the Central Valley of Costa Rica and Antioquia, Colombia also identified rs7868992 as the top signal (P=3.6 × 10(-7) for the combined sample of 1496 cases and 5249 controls following imputation with 1000 Genomes data). This study lays the groundwork for the eventual identification of common TS susceptibility variants in larger cohorts and helps to provide a more complete understanding of the full genetic architecture of this disorder.
Assuntos
Colágenos Fibrilares/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo Único/genética , Síndrome de Tourette/genética , Adolescente , Adulto , Transtorno do Deficit de Atenção com Hiperatividade/etiologia , Transtorno do Deficit de Atenção com Hiperatividade/genética , Estudos de Casos e Controles , Cromossomos Humanos Par 9/genética , Feminino , Genótipo , Humanos , Cooperação Internacional , Masculino , Metanálise como Assunto , Transtorno Obsessivo-Compulsivo/etiologia , Transtorno Obsessivo-Compulsivo/genética , Síndrome de Tourette/complicações , População Branca/genética , Adulto JovemRESUMO
BACKGROUND: Prurigo nodularis Hyde (PN) is a highly pruritic condition due to a vicious circle of repeated itching and scratching. There are no representative clinical studies investigating comorbidities in a large collective of PN patients. OBJECTIVE: This pilot study aimed to investigate the exact distribution of the coexisting diseases in a large representative consecutive cohort of PN patients. METHODS: A total of 108 PN patients (36.1% male; mean age of 61.5 ± 16.7 years) were enrolled in the study. RESULTS: In 87.0% of patients, diseases underlying PN could be established (18.5% skin disease, 7.4% systemic origin, 1.8% neurological diseases, 59.3% mixed origin). Due to several possible causative co-factors, the majority of patients were classified in the group of mixed origin (59.3%). In 53.1% of these patients, at least one dermatological factor was involved in the induction of PN. Interestingly, nearly half (46.3%) of all PN patients had either an atopic predisposition or atopic dermatitis as a single cause of PN (18.5%) or as one co-factor of PN of mixed origin (27.8%). Considering the different underlying diseases, there was no significant age or gender difference. CONCLUSION: PN does not seem to represent a characteristic symptom of one disease only. Multiple pruritogenic diseases are linked to evolution and improvement of PN upon treatment. Atopic predisposition is a major factor in nearly half of PN patients. The large collective of the present study helped detect a broad range of underlying diseases and thus to provide recommendations for rational diagnostics.
Assuntos
Prurigo/etiologia , Dermatopatias/complicações , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Dermatopatias/classificaçãoRESUMO
With a prevalence of 20%, chronic pruritus is a symptom of many diseases with major impact on healthcare costs. The lack of specific therapeutic measures makes the development of new drugs and their testing in clinical trials urgent. It is not possible to measure pruritus in an objective way. For these reasons, it is necessary to have a series of standardized measures to characterize pruritus in a reliable way. Intensity scales such as the visual analog scale (VAS) are most frequently used to document the course of the symptoms. However, for assessing pruritus intensity, VAS is not an optimal instrument, although it cannot be dispensed with. The VAS should be combined with other scales in clinical studies in order to internally test the consistency of data. Other instruments for assessing intensity and course of pruritus are in the process of development. Presently scratch activity and scratch-associated lesions can be documented in a descriptive fashion. There are some studies that have employed devices to document scratch activity; however, methodological studies are not yet available. The patient-benefit index is an indispensable tool in clinical trials. A questionnaire for gathering data on the history and some pruritus-specific parameters has been developed and published. Questionnaires on patient quality of life, anxiety and depression are helpful in obtaining data on other cost-relevant parameters. A questionnaire on the quality of life, for instance, can provide important help in the assessment of the burden of the disease. The results of these questionnaires can be correlated with data on pruritus intensity scales. The relevant questionnaires have been partially digitalized so that they are available immediately as part of patient care. Additional methodological developments and studies are required in order to define a robust set of instruments for measuring pruritus in daily practice and in clinical studies.
Assuntos
Medição da Dor/normas , Dor/diagnóstico , Dor/etiologia , Exame Físico/normas , Guias de Prática Clínica como Assunto , Prurido/complicações , Prurido/diagnóstico , Dermatologia/normas , Humanos , InternacionalidadeRESUMO
As the frequency and characteristics of chronic pruritus in autoimmune dermatoses (AID) have not yet been investigated, the present study aimed at characterizing pruritus in a representative group of patients with AID. A total of 35 patients (80% women) with AID were included, divided into 3 main groups (group 1; n = 19: bullous pemphigoid (BP), pemphigus vulgaris (PV); group 2; n = 9: scleroderma (SSc), morphea (Mo); group 3; n = 7: lupus erythematosus (LE), dermatomyositis (DM). Demographic data and pruritus characteristics were obtained by standardized questionnaires and statistically evaluated by SPSS 20.0. In group 1 (BP/PV) and group 3 (LE/DM), pruritus preceded the initial diagnosis of AID (2.1 ± 7.6 years and 9.5 ± 16.0 years). Patients in group 2 (SSc/Mo) reported pruritus initially 2.8 ± 8.6 years after the initial diagnosis. In group 1 (BP/PV) significantly (p < 0.05) more excoriations and relief by scratching were observed than in groups 2 (SSc/Mo) and 3 (LE/DM). While pruritus occurred as a prodromal symptom of BP/PV and LE/DM, it was only detected once the initial diagnosis of SSc/Mo was made. In contrast to BP/PV, the other forms of AID were associated with mechanically inducible pruritus with dysesthetic qualities. All forms of AID were associated with intensive pruritus which had a significant impact on quality of life.
Assuntos
Doenças Autoimunes/diagnóstico , Doenças Autoimunes/epidemiologia , Coleta de Dados , Prurido/diagnóstico , Prurido/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença Crônica , Comorbidade , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de RiscoRESUMO
Protein equilibrium snapshot by hydrogen/deuterium exchange electrospray ionization mass spectrometry (PEPS-HDX-ESI-MS or PEPS) is a method recently introduced for estimating protein folding energies and rates. Herein we describe the basis for this method using both theory and new experiments. Benchmark experiments were conducted using ubiquitin because of the availability of reference data for folding and unfolding rates from NMR studies. A second set of experiments was also conducted to illustrate the surprising resilience of the PEPS to changes in HDX time, using staphylococcal nuclease and time frames ranging from a few seconds to several minutes. Theory suggests that PEPS experiments should be conducted at relatively high denaturant concentrations, where the protein folding/unfolding rates are slow with respect to HDX and the life times of both the closed and open states are long enough to be sampled experimentally. Upon deliberate denaturation, changes in folding/unfolding are correlated with associated changes in the ESI-MS signal upon fast HDX. When experiments are done quickly, typically within a few seconds, ESI-MS signals, corresponding to the equilibrium population of the native (closed) and denatured (open) states can both be detected. The interior of folded proteins remains largely un-exchanged. Amongst MS methods, the simultaneous detection of both states in the spectrum is unique to PEPS and provides a "snapshot" of these populations. The associated ion intensities are used to estimate the protein folding equilibrium constant (or the free energy change, ΔG). Linear extrapolation method (LEM) plots of derived ΔG values for each denaturant concentration can then be used to calculate ΔG in the absence of denaturant, ΔG(H(2)O). In accordance with the requirement for detection of signals for both the folded and unfolded states, this theoretical framework predicts that PEPS experiments work best at the middle of the denaturation curve where natured and denatured protein molecules are equilibrated at easily detectable ratios, namely 1:1. It also requires that closed and open states have lifetimes measurable in the time frame of the HDX experiment. Because both conditions are met by PEPS, these measurements can provide an accurate assessment of closed/open state populations and thus protein folding energies/rates.
RESUMO
Radionuclides from the reactor accident at the Fukushima Dai-ichi Nuclear Power Plant were observed in the surface air at stations in Hanoi, Dalat, and Ho Chi Minh City (HCMC) in Vietnam, about 4500 km southwest of Japan, during the period from March 27 to April 22, 2011. The maximum activity concentrations in the air measured at those three sites were 193, 33, and 37 µBq m(-3) for (131)I, (13)(4)Cs, and (13)(7)Cs, respectively. Peaks of radionuclide concentrations in the air corresponded to arrival of the air mass from Fukushima to Vietnam after traveling for 8 d over the Pacific Ocean. Cesium-134 was detected with the (134)Cs/(137)Cs activity ratio of about 0.85 in line with observations made elsewhere. The (131)I/(137)Cs activity ratio was observed to decrease exponentially with time as expected from radioactive decay. The ratio at Dalat, where is 1500 m high, was higher than those at Hanoi and HCMC in low lands, indicating the relative enrichment of the iodine in comparison to cesium at high altitudes. The time-integrated surface air concentrations of the Fukushima-derived radionuclides in the Southeast Asia showed exponential decrease with distance from Fukushima.
Assuntos
Poluentes Radioativos do Ar/análise , Desastres , Terremotos , Monitoramento de Radiação/estatística & dados numéricos , Liberação Nociva de Radioativos/história , Tsunamis , Radioisótopos de Césio/análise , Geografia , História do Século XXI , Radioisótopos do Iodo/análise , Japão , Liberação Nociva de Radioativos/estatística & dados numéricos , Espectrometria gama , Fatores de Tempo , VietnãRESUMO
BACKGROUND: Prurigo nodularis (PN) is a highly pruritic condition characterized by multiple hyperkeratotic nodules. Previous immunohistochemical studies demonstrated increased numbers of dermal nerve fibres. OBJECTIVES: Given that the sensation of pruritus is transmitted mainly by thin, unmyelinated epidermal nerves, the aim of our study was to investigate the intraepidermal nerve fibre (IENF) density. METHODS: Biopsies taken from lesional and nonlesional skin of 53 patients (37 women and 16 men; mean ± SD age 60·6 ± 14·9 years) with PN of diverse origin were immunostained for protein gene product 9·5. According to the guideline of the European Federation of Neurological Societies, the IENF density per millimetre was determined and compared with that in 20 healthy volunteers. RESULTS: Lesional and uninvolved PN skin biopsies showed significantly decreased IENF density (P < 0·001) regardless of patient age, origin of PN, intensity or quality of pruritus. CONCLUSIONS: Hypoplasia of epidermal sensory nerves independently of clinical parameters is a new finding in PN and suggests involvement of epidermal nerves in PN pathophysiology. To date, it cannot be ruled out that reduced IENF density is due to repeated scratching. However, the presence of hypoplasia in nonlesional PN skin suggests the presence of a subclinical small fibre neuropathy.
Assuntos
Epiderme/inervação , Fibras Nervosas/patologia , Doenças do Sistema Nervoso Periférico/patologia , Prurigo/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Condução Nervosa , Variações Dependentes do ObservadorRESUMO
Tritium is a radioactive form of hydrogen and is a by-product of energy production in Canadian Deuterium Uranium (CANDU) reactors. The release of this radioisotope into the environment is carefully managed at CANDU facilities in order to minimize radiation exposure to the public. However, under some circumstances, small accidental releases to the environment can occur. The radiation doses to humans and non-human biota from these releases are low and orders of magnitude less than doses received from naturally occurring radioisotopes or from manmade activities, such as medical imaging and air travel. There is however a renewed interest in the biological consequences of low dose tritium exposures and a new limit for tritium levels in Ontario drinking water has been proposed. The Ontario Drinking Water Advisory Council (ODWAC) issued a formal report in May 2009 in response to a request by the Minister of the Environment, concluding that the Ontario Drinking Water Quality Standard for tritium should be revised from the current 7,000 Bq/L level to a new, lower 20 Bq/L level. In response to this recommendation, an international scientific symposium was held at McMaster University to address the issues surrounding this change in direction and the validity of a new policy. Scientists, regulators, government officials, and industrial stakeholders were present to discuss the potential health risks associated with low level radiation exposure from tritium. The regulatory, economic, and social implications of the new proposed limit were also considered.The new recommendation assumed a linear-no-threshold model to calculate carcinogenic risk associated with tritium exposure, and considered tritium as a non-threshold chemical carcinogen. Both of these assumptions are highly controversial given that recent research suggests that low dose exposures have thresholds below which there are no observable detrimental effects. Furthermore, mutagenic and carcinogenic risk calculated from tritium exposure at 20 Bq/L would be orders of magnitude less than that from exposure to natural background sources of radiation. The new proposed standard would set the radiation dose limit for drinking water to 0.0003 mSv/year, which is equivalent to approximately three times the dose from naturally occurring tritium in drinking water. This new standard is incongruent with national and international standards for safe levels of radiation exposure, currently set at 1 mSv/year for the general public. Scientific research from leading authorities on the carcinogenic health effects of tritium exposure supports the notion that the current standard of 7,000 Bq/L (annual dose of 0.1 mSv) is a safe standard for human health.Policy-making for the purpose of regulating tritium levels in drinking water is a dynamic multi-stage process that is influenced by more than science alone. Ethics, economics, and public perception also play important roles in policy development; however, these factors sometimes undermine the scientific evidence that should form the basis of informed decision making. Consequently, implementing a new standard without a scientific basis may lead the public to perceive that risks from tritium have been historically underestimated. It was concluded that the new recommendation is not supported by any new scientific insight regarding negative consequences of low dose effects, and may be contrary to new data on the potential benefits of low dose effects. Given the lack of cost versus benefit analysis, this type of dramatic policy change could have detrimental effects to society from an ethical, economical, and public perception perspective.
RESUMO
BACKGROUND: Pruritus is a frequent symptom in many diseases; its prevalence in German adults is unknown. OBJECTIVE: Our purpose was to assess the prevalence, severity and health care of chronic pruritus in the German working population. METHODS: A cross-sectional observational study was conducted in employees of 144 German companies. Pruritus-specific data were obtained by standardized questions. RESULTS: 11,730 people (53.2% male, 16-70 years, mean = 43.7 years) were suitable for analysis. The point prevalence of chronic pruritus (at least 6 weeks prior to data collection) was 16.8%. The prevalence increased with age from 12.3% (16-30 years) to 20.3% (61-70 years). A quarter of the affected persons had suffered from pruritus for >5 years, 47% had never sought medical advice, and 94% had not undergone any treatment. CONCLUSIONS: Chronic pruritus is a prevalent symptom in the working age population. A high proportion of people affected are not medically treated.