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The dynamics of a tracer particle in a bath of quasi-hard colloidal spheres is studied by Langevin dynamics simulations and mode coupling theory (MCT); the tracer radius is varied from equal to up to seven times larger than the bath particles radius. In the simulations, two cases are considered: freely diffusing tracer (passive microrheology) and tracer pulled with a constant force (active microrheology). Both cases are connected by linear response theory for all tracer sizes. It links both the stationary and transient regimes of the pulled tracer (for low forces) with the equilibrium correlation functions; the velocity of the pulled tracer and its displacement are obtained from the velocity auto-correlation function and the mean squared displacement, respectively. The MCT calculations give insight into the physical mechanisms: At short times, the tracer rattles in its cage of neighbours, with the frequency increasing linearly with the tracer radius asymptotically. The long-time tracer diffusion coefficient from passive microrheology, which agrees with the inverse friction coefficient from the active case, arises from the transport of transverse momentum around the tracer. It can be described with the Brinkman equation for the transverse flow field obtained in extension of MCT, but cannot be recovered from the MCT kernel coupling to densities only. The dynamics of the bath particles is also studied; for the unforced tracer the dynamics is unaffected. When the tracer is pulled, the velocity field in the bath follows the prediction of the Brinkman model, but different from the case of a Newtonian fluid.
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Polymerase chain reaction (PCR) detection has become the gold standard for diagnosis and typing of enterovirus (EV) and human parechovirus (HPeV) infections. Its effectiveness depends critically on using the appropriate sample types and high assay sensitivity as viral loads in cerebrospinal fluid samples from meningitis and sepsis clinical presentation can be extremely low. This study evaluated the sensitivity and specificity of currently used commercial and in-house diagnostic and typing assays. Accurately quantified RNA transcript controls were distributed to 27 diagnostic and 12 reference laboratories in 17 European countries for blinded testing. Transcripts represented the four human EV species (EV-A71, echovirus 30, coxsackie A virus 21, and EV-D68), HPeV3, and specificity controls. Reported results from 48 in-house and 15 commercial assays showed 98% detection frequencies of high copy (1000 RNA copies/5 µL) transcripts. In-house assays showed significantly greater detection frequencies of the low copy (10 copies/5 µL) EV and HPeV transcripts (81% and 86%, respectively) compared with commercial assays (56%, 50%; P = 7 × 10-5 ). EV-specific PCRs showed low cross-reactivity with human rhinovirus C (3 of 42 tests) and infrequent positivity in the negative control (2 of 63 tests). Most or all high copy EV and HPeV controls were successfully typed (88%, 100%) by reference laboratories, but showed reduced effectiveness for low copy controls (41%, 67%). Stabilized RNA transcripts provide an effective, logistically simple and inexpensive reagent for evaluation of diagnostic assay performance. The study provides reassurance of the performance of the many in-house assay formats used across Europe. However, it identified often substantially reduced sensitivities of commercial assays often used as point-of-care tests.
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Infecções por Enterovirus/diagnóstico , Enterovirus/classificação , Parechovirus/classificação , Infecções por Picornaviridae/diagnóstico , RNA Viral/genética , Infecções por Enterovirus/virologia , Europa (Continente) , Dosagem de Genes , Humanos , Meningite Viral/diagnóstico , Tipagem Molecular , Infecções por Picornaviridae/virologia , Kit de Reagentes para Diagnóstico , Reação em Cadeia da Polimerase em Tempo Real , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
The corpus callosum has become a key area of interest for researchers in severe mental illness. Disruptions in fractional anisotropy in the callosum have been reported in schizophrenia and major depressive disorder. No change has been reported in oligodendrocyte density and overall size of the callosum in either illness, suggesting that gross morphology is unchanged, but subtler organisational disruption may exist within this structure. Using high-resolution oil immersion microscopy, we examined the cross-sectional area of the nerve fibre and the axonal myelin sheath; and using standard high-resolution light microscopy, we measured the density of myelinated axons. These measurements were made in the splenium of the corpus callosum. Measures were taken in the sagittal plane in the callosal splenium to contrast with the previous similar examination of the callosal genu. Cases of major depressive disorder had significantly decreased mean myelin cross-sectional area (p = 0.014) per axon in the splenium than in controls or schizophrenia groups. There was no significant change in the density of myelinated axons. The results suggest a clear decrease of myelin in the axons of the callosal splenium in MDD, although this type of neuropathological study is unable to clarify whether this is caused by changes during life or has a developmental origin. In contrast with increased myelin in the callosal genu, this result suggests a longitudinal change in callosal myelination in major depressive disorder not present in normal or schizophrenic brains.
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Axônios/patologia , Corpo Caloso/patologia , Transtorno Depressivo Maior/patologia , Bainha de Mielina/patologia , Bancos de Tecidos , Adulto , Corpo Caloso/diagnóstico por imagem , Transtorno Depressivo Maior/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Modular endoprostheses, so-called "tumour or megaprostheses" are mainly used for limb salvage surgery after resection of malignant soft tissue or a bone tumour. Sometimes, this type of prosthesis is also used for revision surgeries after failed primary joint arthroplasty. Despite continuously improving techniques and quality management systems, periprosthetic infection is one of the most serious complications. AIM OF THE STUDY: Review of the literature in the PubMed data base with the main focus on silver coatings in joint arthroplasty and their effect on infection rate, outcome and patients' safety. RESULTS: The current literature shows that there is a beneficial role of silver coatings in megaprostheses in terms of revision rates for septic complications, especially following tumour resection with bad soft tissue coverage or in (multimorbid) high-risk patients, compared to uncoated implants. DISCUSSION: Based on the results of previous publications examining blood or serum silver concentrations or silver levels in urine, silver coatings do not appear to have side effects, except for local argyria. Continuous monitoring of silver levels in blood or serum is still recommended, and additional long-term studies will be necessary to verify the effectiveness and safety of silver coatings.
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Membros Artificiais , Neoplasias Ósseas , Artroplastia , Neoplasias Ósseas/cirurgia , Humanos , Reoperação/métodos , PrataAssuntos
Ciências do Comportamento , Política Pública , Humanos , Política de Saúde , Organizações , Saúde PúblicaRESUMO
The aim of our study was to project the borders of the flexor retinaculum (FR) onto superficial landmarks since its insufficient splitting is the most common reason for persistence of symptoms after carpal tunnel release. In 60 hands the radial and ulnar styloid processes were linked by a horizontal line and a longitudinal line was laid through the ring finger's radial side. These were intersected resulting in the reference point "A" on the forearm. As the second basing point "B", the radial margin of the ring finger at the palmar digital crease was chosen. Measurement of the FR was carried out with regard to the reference points. The proximal margin of the FR was located at 4% of the reference line A-B starting from point A and extended up to 52% of this total length. Results indicate that splitting alongside the proximal half of line A-B divides the FR completely. Clin. Anat. 30:512-516, 2017. © 2017 Wiley Periodicals, Inc.
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Pontos de Referência Anatômicos , Síndrome do Túnel Carpal/diagnóstico por imagem , Descompressão Cirúrgica/métodos , Endoscopia , Ligamentos Articulares/anatomia & histologia , Idoso , Idoso de 80 Anos ou mais , Cadáver , Síndrome do Túnel Carpal/cirurgia , Feminino , Humanos , Ligamentos Articulares/cirurgia , Masculino , Pessoa de Meia-IdadeRESUMO
Background: Intravitreal anti-VEGF therapy is the gold standard in the treatment of neovascular age-related macular degeneration (nAMD). In recent literature, the benefit of additional photodynamic therapy (PDT) has been debated. The aim of our study was to compare the functional and structural effects of long-term combination therapy with PDT plus ranibizumab with monotherapy with ranibizumab. Material and Methods: In a retrospective study, patients suffering from nAMD were followed up for at least 42 months. Patients were assigned to group A (monotherapy with ranibizumab according to pro re nata [PRN]) or group B (combination therapy with one-time PDT plus ranibizumab according to PRN). The best-corrected visual acuity (BVCA) was evaluated at the starting and end points, together with central retinal thickness (CRT), maximal retinal thickness (MRT) and the maximal diameter of the base of the subretinal plaque in spectral-domain optical coherence tomography (SD-OCT), at the first measurement and at the end point. Results: Group A consisted of 21 eyes (17 patients) and group B consisted of 12 eyes (11 patients). The average follow-up from starting to end point was 64 months and 47 months, from the first measurement of SD-OCT to the end point. Within this period, patients in group A received 19 ± 14 intravitreal injections, and patients in group B received 22 ± 10 intravitreal injections. BCVA at the starting point was 0.31 ± 0.26 in group A and 0.31 ± 0.17 in group B. At the end point, BCVA in group A was 0.29 ± 0.25 (p = 0.405), and in group B 0.25 ± 0.20 (p = 0.142). CRT decreased in group A by 72 ± 178 µm (p = 0.024) and group B by 28 ± 98 (p = 0.1335). MRT decreased in group A by 25 ± 135 µm (p = 0.166) and in group B by 2 ± 118 µm (p = 0.421). The base of the subretinal plaque increased in group A by 32 ± 1468 µm (p = 0.242) and in group B by 748 ± 1024 (p = 0.025). Conclusion: In a long-term follow-up of 5.3 years, patients with nAMD in both groups exhibited good stabilisation of visual acuity. In both groups, retinal thickness decreased and the base of the subretinal plaque increased. With respect to SD-OCT morphological criteria, patients in group A (monotherapy) responded slightly better to therapy than patients in group B (combination group).
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Fotoquimioterapia/métodos , Ranibizumab/administração & dosagem , Tomografia de Coerência Óptica/métodos , Acuidade Visual , Degeneração Macular Exsudativa/tratamento farmacológico , Degeneração Macular Exsudativa/patologia , Idoso , Inibidores da Angiogênese/administração & dosagem , Terapia Combinada/métodos , Feminino , Humanos , Estudos Longitudinais , Masculino , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Degeneração Macular Exsudativa/diagnóstico por imagemRESUMO
The purpose of this paper is to describe the use of toxicokinetic (TK) and toxicodynamic (TD) data in setting acceptable daily exposure (ADE) values and occupational exposure limits (OELs). Use of TK data can provide a more robust exposure limit based on a rigorous evaluation of systemic internal dose. Bioavailability data assist in extrapolating across different routes of exposure to be protective for route-based differences of exposure. Bioaccumulation data enable extrapolation to chronic exposures when the point of departure (PoD) is from a short-term critical study. Applied in the context of chemical-specific adjustment factors (CSAFs), TK data partially replace traditional default adjustment factors for interspecies extrapolation (extrapolation from studies conducted in animals to humans) and intraspecies variability (to account for human population variability). Default adjustments of 10-fold each for interspecies and intraspecies extrapolation are recommended in several guidelines, although some organization recommend other values. Such default factors may overestimate variability for many APIs, while not being sufficiently protective for variability with other APIs. For this reason, the use of chemical specific TK and TD data are preferred. Making full use of existing TK and TD data reduces underlying uncertainties, increases transparency, and ensures that resulting ADEs reflect the best available science.
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Indústria Farmacêutica , Nível de Efeito Adverso não Observado , Exposição Ocupacional/prevenção & controle , Saúde Ocupacional , Preparações Farmacêuticas , Toxicocinética , Animais , Área Sob a Curva , Indústria Farmacêutica/legislação & jurisprudência , Indústria Farmacêutica/normas , Guias como Assunto , Meia-Vida , Política de Saúde , Humanos , Taxa de Depuração Metabólica , Modelos Biológicos , Exposição Ocupacional/efeitos adversos , Exposição Ocupacional/legislação & jurisprudência , Exposição Ocupacional/normas , Saúde Ocupacional/legislação & jurisprudência , Saúde Ocupacional/normas , Preparações Farmacêuticas/classificação , Preparações Farmacêuticas/normas , Formulação de Políticas , Medição de Risco , Especificidade da Espécie , Testes de ToxicidadeRESUMO
BACKGROUND: Elderly patients are under-represented in hepatitis B and C screening approaches, but may be at increased risk for advanced liver disease. We therefore screened a hospitalized elderly population. MATERIALS AND METHODS: 6011 admissions to the department of internal medicine and neurology within one year were screened for HBsAg and anti-HCV (Elecsys(®)-HBsAg and -anti-HCV). Positive anti-HCV results were confirmed with the INNO-LIA™ assay. HCV-RNA was analyzed by real-time PCR in the case of confirmed positive anti-HCV results, HBV-DNA in the confirmed HBsAg positive individuals. RESULTS: Patient´s mean age (62.4 years) was 19 years above that of the average German population. The confirmed HBsAg prevalence was 0.6â%. 34â% (nâ=â12/35) of HBsAg positive cases were newly diagnosed, three of them presented with HBV-DNA levels >â2000âIU/mL. The confirmed anti-HCV prevalence was 0.9â%. 14â% (nâ=â8/56) of anti-HCV positive patients were previously undiagnosed. HCV-RNA was positive in three of them. In newly diagnosed individuals cirrhosis was present in 1/12 of the HBsAg and in 3/8 of the anti-HCV positive individuals. Compared to non-infected controls, the following risk factors were significantly more frequent in infected patients: (i) HBsAg: sexual exposure (20â% vs. 2â%), blood transfusion before 1992 (13â% vs. 6â%), referrals from nursing homes (10â% vs. 1â%). (ii) Anti-HCV: blood transfusion before 1992 (41â% vs. 6â%), IVDU (25â% vs. 0.5â%), organ transplantation (20â% vs. 5â%), hemodialysis (11â% vs. 3â%). CONCLUSIONS: HBsAg and anti-HCV were underdiagnosed in a senescent population, however, only few cases presented with advanced liver disease. Referrals from nursing homes were at increased risk for HBV infection.
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Antígenos de Superfície da Hepatite B/sangue , Hepatite B/epidemiologia , Anticorpos Anti-Hepatite C/sangue , Hepatite C/epidemiologia , Hospitalização/estatística & dados numéricos , Programas de Rastreamento/estatística & dados numéricos , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Estudos de Coortes , Comorbidade , Feminino , Avaliação Geriátrica/métodos , Avaliação Geriátrica/estatística & dados numéricos , Alemanha/epidemiologia , Serviços de Saúde para Idosos/estatística & dados numéricos , Hepatite B/sangue , Hepatite B/diagnóstico , Antígenos de Superfície da Hepatite B/imunologia , Hepatite C/sangue , Hepatite C/diagnóstico , Anticorpos Anti-Hepatite C/imunologia , Humanos , Masculino , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Prevalência , Medição de Risco , Distribuição por Sexo , Centros de Atenção Terciária/estatística & dados numéricosRESUMO
STEEP(TM) was one of the first attachment-based early intervention programs. The program applied findings from the Minnesota Longitudinal Study on Risk and Adaptation to the development of a supportive program for young high-risk mothers and their infants. STEEP's effectiveness was evaluated first in a randomized controlled study launched in 1987. The study showed effects of the one-year intervention on important individual and parenting variables, but not on quality of mother-infant attachment. In the current German study with young mothers at risk for abuse and neglect, a two-year adaptation of STEEP was evaluated within a quasi-experimental design. STEEP mother-infant pairs (N = 78) were compared with pairs who received standard services of the German Child Welfare System (GCWS, N = 29). Compared with GCWS pairs, significantly more mother-infant pairs in the intervention group showed secure attachment patterns in Ainsworth´s Strange Situation when the infants were 12 months of age. At the end of the intervention (infant age = 24 month), attachment security scores derived from Waters' Attachment Q-Sort were in the predicted direction and showed a medium effect size, but did not reach criteria of statistical significance. At both time points, the STEEP group showed significantly fewer signs of attachment disorganization than the comparison group.
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Comportamento Materno , Relações Mãe-Filho/psicologia , Mães/educação , Apego ao Objeto , Poder Familiar/psicologia , Adolescente , Pré-Escolar , Depressão Pós-Parto/psicologia , Feminino , Alemanha , Humanos , Lactente , Estudos Longitudinais , Masculino , Apoio Social , Estresse Psicológico/psicologia , Populações Vulneráveis , Adulto JovemRESUMO
Background: To assess functional and morphological outcomes in patients with chronic recurrent neovascular age-related macular degeneration (nAMD) previously treated with ranibizumab, who were either switched from ranibizumab to aflibercept or received further ranibizumab injections. Methods: Retrospective analysis of eyes with recurrent nAMD previously treated with ranibizumab. On recurrence of the macular oedema, patients had received either 3 injections of aflibercept (2.0 mg) or ranibizumab (0.5 mg) at 4 week intervals. Patients were examined before the first injection and four weeks after the last injection. The main outcome measures included change in visual acuity (VA) in logMAR, subfoveal central retinal thickness (CRT), subretinal fluid (SRF) and height of pigment epithelial detachment (PED height), as well as the maximum height of macular subretinal fluid (SRF max) and of macular pigment epithelial detachment (PED height max) in spectral-domain optical coherence tomography (OCT). Changes in VA and OCT were compared between the two groups to investigate differences in the therapeutic effects of aflibercept and ranibizumab. Results: 60 eyes of 55 patients were included. The aflibercept group (n = 30) and the ranibizumab group (n = 30) showed no statistically significant differences in mean age (p = 0.813), number of prior injections of ranibizumab (p = 0.127) or time since last injection (p = 0.523). Mean VA logMAR improved in both groups, though only in the ranibizumab group was the difference significant (0.50 ± 0.33 to 0.44 ± 0.29 logMAR; p = 0.013; Table 1). CRT decreased in the aflibercept (p = 0.133) and ranibizumab groups (p = 0.043). PED height was reduced in both groups (aflibercept p = 0.068; ranibizumab p = 0.241). SRF, SRF max and PED height max showed statistically significant decreases in both groups. Comparison of the aflibercept and the ranibizumab groups showed no statistically significant differences between the two groups in change in VA logMAR (p = 0.680), CRT (p = 0.882), SRF (p = 0.871), PED height (p = 0.524), SRF max (p = 0.940) or PED height max (p = 0.762). Conclusions: Aflibercept and ranibizumab were similarly effective in improving visual acuity and morphological parameters of patients with recurrent nAMD after four months. There were no statistically significant differences in the therapeutic effects of the two drugs.
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Degeneração Macular/diagnóstico , Degeneração Macular/tratamento farmacológico , Ranibizumab/administração & dosagem , Receptores de Fatores de Crescimento do Endotélio Vascular/administração & dosagem , Proteínas Recombinantes de Fusão/administração & dosagem , Transtornos da Visão/prevenção & controle , Inibidores da Angiogênese/administração & dosagem , Feminino , Humanos , Degeneração Macular/patologia , Masculino , Estudos Retrospectivos , Resultado do Tratamento , Transtornos da Visão/diagnóstico , Acuidade Visual/efeitos dos fármacosRESUMO
Treatment is usually indicated for symptomatic vitreomacular traction (VMT) with or without a full thickness macular hole (FTMH) and without spontaneous resolution. Ultrastructural parameters are evaluated by SD-OCT, in order to classify the vitreoretinal interface and to estimate the success rate of treatment. The resolution rate after therapy with intravitreal Jetrea® (Ocriplasmin) is high (up to 70â%) in patients with symptomatic focal vitreomacular traction (≤ 1500 µm) with or without a macular hole (≤ 250 µm) and with no epiretinal membrane (ERM), but depends on the exact baseline analysis. All other patients with idiopathic traction retinopathy should be treated by minimal invasive pars plana vitrectomy (MIVI). Vitreoretinal surgery effectively removes traction and gives a high closure rate of a full thickness macular hole (FTMH, 90 to 100â%). It is now a very safe procedure with few side effects. Despite a low risk profile (cataract, retinal tear etc.) the indication for surgery needs to take the safety profile into account. Therefore vitrectomy is only indicated in symptomatic patients complaining of blurred vision, VA reduction and metamorphopsia. Vitrectomy is also indicated in patients whose treatment by pharmacologic vitreolysis has failed.
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Descolamento Retiniano/terapia , Perfurações Retinianas/terapia , Aderências Teciduais/terapia , Descolamento do Vítreo/terapia , Terapia Combinada/métodos , Medicina Baseada em Evidências , Fibrinolisina/administração & dosagem , Fibrinolíticos/administração & dosagem , Humanos , Fragmentos de Peptídeos/administração & dosagem , Descolamento Retiniano/complicações , Descolamento Retiniano/diagnóstico , Descolamento Retiniano/patologia , Perfurações Retinianas/complicações , Perfurações Retinianas/diagnóstico , Perfurações Retinianas/patologia , Aderências Teciduais/complicações , Aderências Teciduais/diagnóstico , Aderências Teciduais/patologia , Tomografia de Coerência Óptica/métodos , Resultado do Tratamento , Vitrectomia/métodos , Descolamento do Vítreo/complicações , Descolamento do Vítreo/patologiaRESUMO
BACKGROUND: SD-OCT is an important tool in the diagnosis of macular oedema (ME) due to retinal vein occlusion (RVO). Its high resolution makes it possible to distinguish various morphological characteristics and differences. The aim of this study is to evaluate the correlation between morphological patterns and the development of visual acuity (VA) after intravitreal treatment of ME due to RVO. METHODS: 81 patients on intravitreal treatment (dexamethasone: n = 53/ranibizumab: n = 28) due to ME associated with branch and central retinal vein occlusion ( BRVO: n = 38/CRVO: n = 43) were retrospectively reviewed. Preoperative SD-OCT images were analysed by vitreous adhesion, epiretinal membranes, foveal contour, height of intraretinal cystoid spaces, inner and outer segment integrity and presence of subretinal fluid. The influence of these patterns on VA improvement was analysed. RESULTS: In almost every morphological pattern, the data were highly variable. Therapy was effective, with a medium gain in VA of 9.51 letters ETDRS (dexamethasone: 9.62 letters/ranibizumab: 9.29 letters). The improvement in VA in patients with small intraretinal cystoid spaces (thickness ≤ 250 µm) was 19.44 letters ETDRS, compared to 7.23 letters ETDRS in patients with confluent cystoid spaces (p = 0.009). Patients with a convex fovea exhibited more pronounced reduction in central retinal thickness (CRT) (p = 0.004). CONCLUSION: Analysis of OCT has concentrated on demonstrating oedema and CRT. Our data indicate that detailed OCT morphology and the size of intraretinal cystoid spaces offer important information about VA prognosis after intravitreal therapy in ME due to RVO.
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Dexametasona/administração & dosagem , Edema Macular/patologia , Edema Macular/terapia , Ranibizumab/administração & dosagem , Oclusão da Veia Retiniana/patologia , Oclusão da Veia Retiniana/terapia , Inibidores da Angiogênese/administração & dosagem , Monitoramento de Medicamentos/métodos , Feminino , Humanos , Injeções Intravítreas , Edema Macular/etiologia , Masculino , Prognóstico , Reprodutibilidade dos Testes , Oclusão da Veia Retiniana/complicações , Estudos Retrospectivos , Sensibilidade e Especificidade , Tomografia de Coerência Óptica , Resultado do Tratamento , Acuidade Visual/efeitos dos fármacosRESUMO
INTRODUCTION: Despite numerous efforts, out-of-hospital cardiac arrest (OHCA) survival has not significantly increased in recent decades. The first telephone-assisted cardiopulmonary resuscitation (T-CPR) studies were published in the 1980s, but only in the last decade has TCPR been implemented in dispatch centers. TCPR is still not available in all dispatch centers and no national or international TCPR recommendations are available. METHODS: Studies from PubMed were identified and evaluated. Preliminary information from the European Dispatch Center Survey (EDiCeS) is also included. RESULTS: In all, 42 studies were included. TCPR is implemented in 87.6 % of those dispatch centers which have joined the not-yet published EDiCeS. According to German Resuscitation Registry data, about 10 % of OHCA patients received TCPR in 2014. Agonal breathing is the leading cause for nonrecognition of OHCA by the dispatcher. Sensitivity of OHCA recognition by the dispatcher is about 75 %, whereby 8-45 % of these patients were not in cardiac arrest. The time interval from call to first compression is 140-328 s. Instructing rescue breathing by telephone is time consuming, leads to extensive hands-off times, and often to ineffective ventilation; therefore, rescue breathing is not indicated in adults with primary cardiac arrest. Studies showed improved survival with standardized TCPR implementation. CONCLUSION: T-CPR is established in many dispatch centers. However, emergency call interrogation and TCPR vary between dispatch centers and are often performed without evaluation. International recommendations with standardized quality control are necessary and may lead to improved survival.
RESUMO
BACKGROUND: Abnormalities in the anterior inter-hemispheric connectivity have previously been implicated in major depressive disorder. Disruptions in fractional anisotropy in the callosum and fornix have been reported in schizophrenia and major depressive disorder. Oligodendrocyte density and overall size of the callosum and fornix show no alteration in either illness, suggesting that gross morphology is unchanged but more subtle organizational disruption may exist within these brain regions in mood and affective disorders. METHOD: Using high-resolution oil-immersion microscopy we examined the cross-sectional area of the nerve fibre and the axonal myelin sheath, and using standard high-resolution light microscopy we measured the density of myelinated axons. These measurements were made in the genu of the corpus callosum and the medial body of the fornix at its most dorsal point. Measures were taken in the sagittal plane in the callosal genu and in the coronal plane at the most dorsal part of the fornix body. RESULTS: Cases of major depressive disorder had significantly greater mean myelin cross-sectional area (p = 0.017) and myelin thickness (p = 0.004) per axon in the genu than in control or schizophrenia groups. There was no significant change in the density of myelinated axons, and no changes observed in the fornix. CONCLUSION: The results suggest a clear increase of myelin in the axons of the callosal genu in MDD, although this type of neuropathological study is unable to clarify whether this is caused by changes during life or has a developmental origin.
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Corpo Caloso/patologia , Transtorno Depressivo Maior/patologia , Bainha de Mielina/patologia , Fibras Nervosas Mielinizadas/patologia , Esquizofrenia/patologia , Adulto , Encéfalo/patologia , Estudos de Coortes , Depressão , Feminino , Humanos , Londres , Masculino , Microscopia de Polarização , Pessoa de Meia-Idade , Análise de Regressão , Bancos de TecidosRESUMO
Actin binding proteins (ABPs) not only set the structure of actin filament assemblies but also mediate the frequency-dependent viscoelastic moduli of cross-linked and bundled actin networks. Point mutations in the actin binding domain of those ABPs can tune the association and dissociation dynamics of the actin/ABP bond and thus modulate the network mechanics both in the linear and non-linear response regime. We here demonstrate how the exchange of a single charged amino acid in the actin binding domain of the ABP fascin triggers such a modulation of the network rheology. Whereas the overall structure of the bundle networks is conserved, the transition point from strain-hardening to strain-weakening sensitively depends on the cross-linker off-rate and the applied shear rate. Our experimental results are consistent both with numerical simulations of a cross-linked bundle network and a theoretical description of the bundle network mechanics which is based on non-affine bending deformations and force-dependent cross-link dynamics.
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Actinas/química , Proteínas de Transporte/química , Proteínas dos Microfilamentos/química , Eletricidade Estática , Actinas/metabolismo , Animais , Sítios de Ligação , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Humanos , Proteínas dos Microfilamentos/genética , Proteínas dos Microfilamentos/metabolismo , Mutação , Ligação Proteica , CoelhosRESUMO
BACKGROUND: The aim of this study was to investigate alterations in the neurosensory retinal morphology secondary to acute retinal ischaemic conditions. The observations were documented by spectral domain optical coherence tomography (SD-OCT, Heidelberg Engineering) and fundus autofluorescence (FAF) imaging. In addition, the occurrence of an additional hyperrefelctive band in the outer corneal layers is described. This observation was made during the evaluation of OCT images of patients with an acute loss of vision due to retinal ischaemia. PATIENTS/METHOD: SD-OCT images and FAF were used to observe the retinal structure of 26 subjects (36 to 96 years) with acute monocular visual impairment due to central retinal artery occlusion (CRAO), branch retinal artery occlusion (BRAO), anterior ischaemic optic neuropathy (AION) or impending central retinal vein occlusion were included. The main focus of attention was set on the transition of the outer nuclear layer (ONL) to outer plexiform layer (OPL). Furthermore measurements of the retinal thickness at the fovea, parafoveal and within the retinal layers were acquired and compared to corresponding points of the non-affected eyes. SD-OCT images were acquired with a combined SD-OCT and scanning laser ophthalmoscope (cSLO) imaging system using a linear cross hair scan and a 6 line radial scan of 6 mm length (ART mode on; average of 20 frames). RESULTS: SD-OCT revealed an additional highly reflective band located within the OPL. Morphological characteristics of this hyperdense band were a decreasing intensity with distance from the fovea, partially segmental occurrence and manifestation limited in time. FAF showed areas of increased and decreased signal intensity within the vessel arcade at the posterior pole. The regions of decreased FAF corresponded to perivenous regions and resemble the "frosted branches" sign seen in fluorescein angiography in patients with ocular ischaemia. CONCLUSIONS: The additional hyperreflective band observed in SD-OCT could represent a marker for retinal ischaemia in subjects without the presence of a complete vascular occlusion. The mid retinal localisation of the band within the OPL is situated at the locus of transition from retinal to choroidal oxygen supply where oxygen diffusion is weakest. Histopathologically the observed structure could represent activated microglial tissue induced by the hypoxia driven upregulation of inflammatory molecules aimed at ischaemia repair.
Assuntos
Angiofluoresceinografia/métodos , Isquemia/patologia , Retina/patologia , Vasos Retinianos/patologia , Retinoscopia/métodos , Tomografia de Coerência Óptica/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Aumento da Imagem/métodos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: High-dose corticosteroids are currently recommended for idiopathic sudden sensorineural hearing loss (ISSNHL) treatment. Intratympanic injections (ITI) are of growing importance, especially in cases of therapy resistance. The selection of patients for this procedure in SSNHL has not been adequately examined so far. STUDY DESIGN: A total of 77 patients with ISSNHL after ineffective systemic pretreatment underwent intratympanic administration of dexamethasone and hyaluronic acid. Improvement after treatment was determined by pure tone audiometry for both ears before and of the treated ear after ITI. RESULTS: In this study 34 female and 43 male patients with mean age of 57 years showed a pre-ITI hearing loss of 35 dB in the lower frequencies and 69 dB in the higher frequencies. The mean hearing gain was 10 dB and the response rate was 62%. Absolute hearing gain revealed significant improvements at 500 Hz, 1 kHz and 2 kHz. Under inclusion of contralateral thresholds there were hardly any differences up to 4 kHz. In a detailed analysis of responders moderate improvements could be observed even in higher frequencies. Overall, no relevant adverse events occurred. CONCLUSION: Treatment of ISSNHL resistant to systemic regimens by ITI of steroids provides an option that offers additional prospects of auditory improvement for affected patients. The presented results indicate that these modalities are also valid for patients with pancochlear ISSNHL.
Assuntos
Corticosteroides/administração & dosagem , Dexametasona/administração & dosagem , Perda Auditiva Súbita/diagnóstico , Perda Auditiva Súbita/tratamento farmacológico , Injeção Intratimpânica/métodos , Atenção Secundária à Saúde/métodos , Doença Aguda , Adjuvantes Imunológicos/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Anti-Inflamatórios/administração & dosagem , Feminino , Humanos , Ácido Hialurônico/administração & dosagem , Masculino , Pessoa de Meia-Idade , Falha de Tratamento , Resultado do TratamentoRESUMO
Small axons far outnumber larger fibers in the corticospinal tract, but the function of these small axons remains poorly understood. This is because they are difficult to identify, and therefore their physiology remains obscure. To assess the extent of the mismatch between anatomic and physiological measures, we compared conduction time and velocity in a large number of macaque corticospinal neurons with the distribution of axon diameters at the level of the medullary pyramid, using both light and electron microscopy. At the electron microscopic level, a total of 4,172 axons were sampled from 2 adult male macaque monkeys. We confirmed that there were virtually no unmyelinated fibers in the pyramidal tract. About 14% of pyramidal tract axons had a diameter smaller than 0.50 µm (including myelin sheath), most of these remaining undetected using light microscopy, and 52% were smaller than 1 µm. In the electrophysiological study, we determined the distribution of antidromic latencies of pyramidal tract neurons, recorded in primary motor cortex, ventral premotor cortex, and supplementary motor area and identified by pyramidal tract stimulation (799 pyramidal tract neurons, 7 adult awake macaques) or orthodromically from corticospinal axons recorded at the mid-cervical spinal level (192 axons, 5 adult anesthetized macaques). The distribution of antidromic and orthodromic latencies of corticospinal neurons was strongly biased toward those with large, fast-conducting axons. Axons smaller than 3 µm and with a conduction velocity below 18 m/s were grossly underrepresented in our electrophysiological recordings, and those below 1 µm (6 m/s) were probably not represented at all. The identity, location, and function of the majority of corticospinal neurons with small, slowly conducting axons remains unknown.
Assuntos
Axônios/ultraestrutura , Condução Nervosa , Tratos Piramidais/fisiologia , Tempo de Reação , Animais , Axônios/fisiologia , Macaca fascicularis , Macaca mulatta , Masculino , Fibras Nervosas Mielinizadas/fisiologia , Fibras Nervosas Mielinizadas/ultraestrutura , Tratos Piramidais/ultraestruturaRESUMO
The performance of accelerators profits from phase-space tailoring by coupling of degrees of freedom. Previously applied techniques swap the emittances among the three degrees but the set of available emittances is fixed. In contrast to these emittance exchange scenarios, the emittance transfer scenario presented here allows for arbitrarily changing the set of emittances as long as the product of the emittances is preserved. This Letter is the first experimental demonstration of transverse emittance transfer along an ion beam line. The amount of transfer is chosen by setting just one single magnetic field value. The envelope functions (beta) and slopes (alpha) of the finally uncorrelated and repartitioned beam at the exit of the transfer line do not depend on the amount of transfer.