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ZUSAMMENFASSUNGSynkopen bilden bei älteren Menschen häufige Sturzursachen. Die beste Sturzprophylaxe besteht in der ätiologischen Abklärung und Behandlung des Synkopenleidens. Die aktuellen Synkopenleitlinien der Deutschen Gesellschaft für Neurologie empfehlen bei Synkopenverdacht zunächst eine hypothesenorientierte Basisdiagnostik, in deren Zentrum die Anamnese mit einer sorgfältigen Exploration der verschiedenen Phasen des Ablaufes einer vorübergehenden Bewusstlosigkeit steht. Zur Basisdiagnostik gehören ferner ein 12-Kanal-EKG und Blutdruckmessungen im Liegen und im Stehen (aktiver Stehtest). Vasovagale Synkopen können bereits nach Anamnese und ohne weitere Zusatzdiagnostik diagnostiziert werden, wenn die Ohnmachten in typischen Situationen (z. B. Verletzungskontext) auftreten und ihnen Prodromi wie Wärmegefühl oder Schwitzen vorausgehen. Bei älteren Patienten bilden orthostatische Blutdruckabfälle durch eine zentrale oder periphere Schädigung des autonomen Nervensystems einen häufigen Synkopenmechanismus, weshalb der aktive Stehtest besonders beim älteren Menschen oft weitere Zusatzdiagnostik überflüssig macht.

Purpose: Epstein–Barr virus (EBV) infection and a family history of nasopharyngeal carcinoma (NPC) are associated with NPC risk. We examined the risk associated with EBV markers and their clinical utility to identify NPC susceptibles within high-risk NPC families.Experimental Design: We evaluated antibody titers against viral capsid antigen (VCA) IgA, EBV nuclear antigen-1 (EBNA1) IgA, and DNase among unaffected relatives of NPC cases from 358 multiplex families in Taiwan. Incident NPC cases were identified via linkage to the National Cancer Registry. Clinical examinations of 924 individuals were also done to identify occult, asymptomatic NPC. Baseline EBV serology was used to estimate NPC risk using rate ratios with 95% CI. Associated sensitivity/specificity and receiver operating characteristic (ROC) curves were calculated.Results: A total of 2,444 unaffected individuals with 15,519 person-years (6.5 years median follow-up) yielded 14 incident NPC cases (nearly 11 times the general population rate). The absolute rate of NPC among anti-EBV EBNA1 IgA seropositives using a standard positivity cutoff versus an optimized cutoff point defined by ROC analyses was 265/100,000 person-years with a 4.7-fold increased risk of NPC (95% CI: 1.4–16) and 166/100,000 person-years with a 6.6-fold increase (95% CI: 1.5–61), respectively. Sensitivity and specificity using the optimized positivity cutoff points were 85.7% and 51.2%, respectively. It is estimated that active evaluation of 49% of individuals from high-risk NPC families seropositive for this marker could lead to earlier detection of up to 86% of NPC cases. Risks associated with the other three EBV markers were weaker.Conclusions: Future efforts are needed to identify susceptibility markers among high-risk NPC families that maximize both sensitivity and specificity. Clin Cancer Res; 17(7); 1906–14. ©2011 AACR.

Supplementary Tables S1-S2.

The radioisotope 26Al is a key observable for nucleosynthesis in the Galaxy and the environment of the early Solar System. To properly interpret the large variety of astronomical and meteoritic data, it is crucial to understand both the nuclear reactions involved in the production of 26Al in the relevant stellar sites and the physics of such sites. These range from the winds of low- and intermediate-mass asymptotic giant branch stars; to massive and very massive stars, both their Wolf–Rayet winds and their final core-collapse supernovae (CCSN); and the ejecta from novae, the explosions that occur on the surface of a white dwarf accreting material from a stellar companion. Several reactions affect the production of 26Al in these astrophysical objects, including (but not limited to) 25Mg(p, γ)26Al, 26Al(p, γ)27Si, and 26Al(n, p/α). Extensive experimental effort has been spent during recent years to improve our understanding of such key reactions. Here we present a summary of the astrophysical motivation for the study of 26Al, a review of its production in the different stellar sites, and a timely evaluation of the currently available nuclear data. We also provide recommendations for the nuclear input into stellar models and suggest relevant, future experimental work.

This analysis examined the clinical and histopathological characteristics of white and red oral mucosal lesions and patient lifestyle behaviors to understand how the lesions changed over 19-23 years, including among patients who developed oral and pharyngeal cancer.Seventy-five individuals with red and/or white oral mucosal lesions with clinical diagnoses of smokeless tobacco lesions, leukoplakia, erythroplakia, lichen planus, ulcer, and virus-associated lesions were identified in six Veterans Affairs Medical Center Dental Clinics (VAMC) from 1996 to 2001. Biopsy results and patients' sociodemographic, medical, and tobacco/alcohol use characteristics were obtained. Study dentists used standardized forms to capture information about the lesions. Study participants were re-examined at intervals through January 2002. In 2020, a retrospective review of VAMC and public records ascertained whether participants developed oral cancer or died.The most common red or white oral mucosal lesions among the 75 study participants were leukoplakia (36.0%), smokeless tobacco lesions (26.7%), virus-associated lesions (18.7%), and lichen planus (16.0%). Lesions in 11% of participants with leukoplakia and one-third of participants with lichen planus persisted for 5 years or more. Dysplasia was present in four participants with leukoplakia. Seventeen percent of participants developed a new white or red oral mucosal lesion. Five patients (6.1%) developed oral or pharyngeal cancer, four among participants with leukoplakia (one with prior dysplasia) and one among participants with lichen planus. Four of the cancers developed 6-20 years after enrollment, and only one was at the original lesion site.The occurrence of oral and pharyngeal cancers in some study participants with white and red oral mucosal lesions many years after enrollment reinforces the need for patients, dentists, and health care systems to have better methods to identify and assess the malignant potential of oral lesions, monitor patients over time, and intercept high-risk oral lesions before they become cancerous.

Embolism as a cause of stroke is widely neglected in Moyamoya angiopathy (MMA), and recommendations for use of antiplatelet therapy (APT) vary. We examined the presence of microembolic signals (MES) during transcranial Doppler (TCD) monitoring and assessed the effects of APT on the occurrence of MES in MMA.We retrospectively analysed patients with MMA treated at our centre between 2011 and 2021. TCD was performed at first presentation and at most visits, while number of visits varied between individual patients. TCD was performed for 30 min bilaterally. Patient demographics, vascular risk factors, and antiplatelet treatment were collected from each clinic visit and ischemic and haemorrhagic episodes were captured as recorded during follow-up visits.209 patients were included in the analysis (mean age 38.7 ± 15.3, 28% male). 21 patients with 27 MES-positive TCD examinations were identified (10%). Patient characteristics were similar in MES-positive and MES-negative groups. However, recent ischemic events were detected at a significantly higher rate in MES-positive patients (42.9% vs 4.8%, p 0.001). After MES detection, change of antiplatelet drug regime was performed, leading to loss of MES in all cases. Dual APT was preferably used in the MES-positive group (p 0.001) but no significant difference of haemorrhage during follow-up-visits was observed. Reduction of APT before bypass-surgery triggered MES in four patients.APT is required in patients with MMA. MES monitoring may help to identify risk patients in need of intensified APT.

Unklare kurze Ohnmachten sollten bis zur Klarung der Ursache als TLOC („transient loss of consciousness“) bezeichnet werden. Nur TLOC durch plotzlichen Hirnperfusionsabfall werden als Synkopen bezeichnet. Entscheidende diagnostische Hinweise liefern die gezielte Exploration der verschiedenen Phasen im Ohnmachtsablauf sowie kliniknahe Methoden wie die Bestimmung von Blutdruck/Puls im Liegen und Stehen (aktiver Stehtest) und Elektrokardiographie. Am haufigsten sind die vasovagalen Synkopen, die bei jungeren Menschen uberwiegen und zumeist harmlos ablaufen. Die neurogene orthostatische Hypotension ist Ursache fur Synkopen, die kurz nach dem Hinstellen auftreten. Sie dominiert bei alteren Personen und entsteht oft durch eine Dysautonomie im Rahmen einer neurologischen Grunderkrankung wie einem Parkinson-Syndrom oder einer autonomen Neuropathie. Bei seltenen vasovagalen Synkopenauslosern wie Schlucken oder Husten sollte nach internistischen Grunderkrankungen gefahndet werden.

The coordination of lipid messenger signaling with cytoskeletal regulation is central to many organelle-specific regulatory processes. This coupling often depends on the function of multidomain scaffolds that orchestrate transient interactions among multiple signaling intermediates and regulatory proteins on organelles. The number of possible scaffold interaction partners and the ability for these interactions to occur at different timescales makes investigations of scaffold functions challenging. This work employs live cell imaging to probe how the multidomain scaffold IQ motif containing GTPase activating protein 1 (IQGAP1) coordinates the activities of proteins affecting local actin polymerization, membrane processing, and phosphoinositide signaling. Using endosomes that are confined by a local actin network as a model system, we demonstrate that IQGAP1 can transition between different actin and endosomal membrane tethered states. Fast scaffold binding/disassociation transitions are shown to be driven by interactions between C-terminal scaffold domains and Rho GTPases at the membrane. Fluctuations in these binding modes are linked to negative regulation of actin polymerization. Although this control governs core elements of IQGAP1 dynamics, actin binding by the N-terminal calponin homology domain of the scaffold is shown to help the scaffold track the temporal development of endosome membrane markers, implying actin associations bolster membrane and actin coordination. Importantly, these effects are not easily distilled purely through standard (static) co-localization analyses or traditional pathway perturbations methods and were resolved by performing dynamic correlation and multiple regression analyses of IQGAP1 scaffold mutants. Using these capabilities with pharmacological inhibition, we provide evidence that membrane tethering is dependent on the activities of the lipid kinase phosphoinositide 3-kinase in addition to the Rho GTPases Rac1 and Cdc42. Overall, these methods and results point to a scaffold tethering mechanism that allows IQGAP1 to help control the amplitude of phosphoinositide lipid messenger signaling by coordinating signaling intermediate activities with the development and disassembly of local actin cytoskeletal networks.

OBJECTIVEDespite significant improvement in spinal cord function after in utero spina bifida (SB) repair compared with traditional postnatal repair, over half of the children who undergo this procedure do not benefit completely. This lack of benefit has been attributed to closure methods of the defect, with subsequent spinal cord tethering at the repair site. Hence, a regenerative patch or material with antiinflammatory and anti-scarring properties may alleviate comorbidities with improved outcomes. The authors’ primary objective was therefore to compare cryopreserved human umbilical cord (HUC) versus acellular dermal matrix (ADM) patches for regenerative repair of in utero SB lesions in an animal model.METHODSIn vivo studies were conducted in retinoic acid–induced SB defects in fetuses of Sprague-Dawley rats. HUC or ADM patches were sutured over the SB defects at a gestational age of 20 days. Repaired SB defect tissues were harvested after 48–52 hours. Tissue sections were immunofluorescently stained for the presence of neutrophils, macrophages, keratinocytes, meningeal cells, and astrocytes and for any associated apoptosis. In vitro meningeal or keratinocyte cell coculture experiments with the ADM and HUC patches were performed. All experiments were scored quantitatively in a blinded manner.RESULTSNeutrophil counts and apoptotic cells were lower in the HUC-based repair group (n = 8) than in the ADM patch repair group (n = 7). In the HUC patch repair group, keratinocytes were present on the outer surface of the patch, meningeal cells were present on the inner surface of the patch adjacent to the neural placode, and astrocytes were noted to be absent. In the ADM patch repair group, all 3 cell types were present on both surfaces of the patch. In vitro studies showed that human meningeal cells grew preferentially on the mesenchymal side of the HUC patch, whereas keratinocytes showed tropism for the epithelial side, suggesting an inherent HUC-based cell polarity. In contrast, the ADM patch studies showed no polarity and decreased cellular infiltration.CONCLUSIONSThe HUC patch demonstrated reduced acute inflammation and apoptosis together with superior organization in regenerative cellular growth when compared with the ADM patch, and is therefore likely the better patch material for in utero SB defect repair. These properties may make the HUC biomaterial useful as a “meningeal patch” during spinal cord surgeries, thereby potentially reducing tethering and improving on spinal cord function.

This chapter describes the sensory innervation of the face and head, focusing on anatomical substrates of clinical features that characterize cranial neuralgias. It draws attention to the key role of the caudal part of the trigeminal spinal nucleus and additional roles of the hypothalamus, descending modulation, and the parasympathetic system. The chapter provides an overview of neural excitability together with reasoning of how it can lead to various manifestations of cranial neuralgias. High-throughput ‘whole-genome sequencing’ studies demonstrate that rare mutations in genes involved in a wide range of neuronal functions underlie the risk for developing trigeminal neuralgia. Although still at an early stage, this research strongly suggests that most patients have inherited protein-changing mutations in several genes and that functionally different groups of genes are associated with different clinical subtypes distinguished by sex, age of onset, and presence of neurovascular compression.

This study explored the effect of a structured therapeutic horticulture (TH) program on depression symptoms and quality of life indicators for individuals receiving inpatient electroconvulsive therapy (ECT) for major depressive disorders (MDD). Self-reported measures of depressive symptomatology (PHQ9, BDI-II) and quality of life (SF-36) were employed to compare intervention (n = 25) and control groups (n = 27), with the intervention group attending TH sessions for one-hour periods, twice per week, in addition to standard inpatient care associated with ECT received by both groups. All patients were assessed at admission, and after two weeks' time or prior to discharge, during which the intervention group participated in a minimum of four TH sessions. Sessions were led by a horticultural therapist in an accessible on-campus greenhouse. Both groups improved significantly between assessment times one and two on both measures of depression, with a statistically significant difference in change scores for the BDI-II only, favoring the control over the intervention group (16.5, s.d. 12.78 versus 9.6, s.d. 10.15; p = 0.36). Both groups improved significantly on four of eight SF-36 subscales during the same period. A statistically significant difference in change scores was found for the Role Limitations-Physical Health (RLPH) subscale, where the intervention group improved between assessment periods, whereas the control group worsened (16.0, s.d.48.8 versus -9.3, s.d. 33.4; p = .033). Although quantifying group changes or improvement for individuals receiving intensive treatment for major depressive disorders (ECT) by the addition of an adjunct therapy is difficult, this study provides a basic premise for the consideration of various therapeutic horticulture settings to achieve therapeutic benefits through TH.

BACKGROUND: Genetic variation in the catechol-O-methyltransferase (COMT) gene is associated with sensitivity to both acute experimental pain and chronic pain conditions. Four single nucleotide polymorphisms (SNPs) have traditionally been used to infer three common haplotypes designated as low, average and high pain sensitivity and are reported to affect both COMT enzymatic activity and pain sensitivity. One mechanism that may partly explain individual differences in sensitivity to pain is conditioned pain modulation (CPM). We hypothesized that variation in CPM may have a genetic basis. METHODS: We evaluated CPM in 77 healthy pain-free Caucasian subjects by applying repeated mechanical stimuli to the dominant forearm using 26-g von Frey filament as the test stimulus with immersion of the non-dominant hand in hot water as the conditioning stimulus. We assayed COMT SNP genotypes by the TaqMan method using DNA extracted from saliva. RESULTS: SNP rs4680 (val(158)met) was not associated with individual differences in CPM. However, CPM was associated with COMT low pain sensitivity haplotypes under an additive model (p = 0.004) and the effect was independent of gender. CONCLUSIONS: We show that, although four SNPs are used to infer COMT haplotypes, the low pain sensitivity haplotype is determined by SNP rs6269 (located in the 5′ regulatory region of COMT), suggesting that inherited variation in gene expression may underlie individual differences in pain modulation. Analysis of 13 global populations revealed that the COMT low pain sensitivity haplotype varies in frequency from 13% to 44% and showed that two SNPs are sufficient to distinguish all COMT haplotypes in most populations.

Background Genetic and environmental factors are important determinants of nasopharyngeal carcinoma (NPC). NPC is associated with Epstein-Barr virus (EBV) infection. Studies have reported familial aggregation of NPC, but evidence has been mixed for elevated rates of cancers other than NPC. Methods The authors reassessed their previous evaluation of familial aggregation of cancer in 348 high-risk Taiwanese multiplex families with 2 or more NPC cases enrolled between 1980 and 2003. Participants were linked to the Taiwan National Cancer Registry and National Death Registry to identify cancers. Results In all, 2590 individuals contributed 37,959 person-years over an average of 15 years of follow-up; 314 incident cancers were identified. The authors computed multiple primary standardized incidence ratios (MP-SIRs) to evaluate the overall risk and the risk of infection-associated, EBV-associated, and individual cancers. The overall MP-SIR was 1.24 (95% confidence interval [CI], 1.10-1.38). The exclusion of excess NPC risk led to an overall MP-SIR of 1.11 (95% CI, 0.98-1.25). Similarly, the risk of cancers associated with infectious agents was driven by the excess in NPC, and its exclusion led to an MP-SIR of 1.22 (95% CI, 0.99-1.48) for infection-associated cancers and to an MP-SIR of 1.18 (95% CI, 0.72-1.82) for EBV-associated cancers. The authors observed a significant excess of second cancers among NPC cases (oral cancer, mouth cancer, tongue cancer, gum cancer, nasal cavity cancer, bone cancer, and non-Hodgkin lymphoma). Conclusions This reassessment of the largest NPC multiplex family study confirms the presence of NPC coaggregation within families in Taiwan but does not provide evidence for a broader familial syndrome involving NPC and other tumors. Among NPC cases, elevated rates of secondary cancers, mostly at the, head and neck and hematopoietic cancers suggest radiation treatment effects on subsequent cancer risk.

Background Localized aggressive periodontitis (LAgP) occurs in 2% of African-American adolescents but only 0.15% of white adolescents. First molars and incisors are affected by rapid onset and progression. Methods This nonsystematic critical review evaluated published data for LAgP and chronic periodontitis (CP), focusing on potential differences in epidemiology, microbiology, immunology, genetics, and response to therapy. Results LAgP differs from CP by localization to incisors and first molars, early onset and rapid progression in adolescents and young adults, and a 10-fold higher prevalence in populations of African or Middle Eastern origin, often with strong familial aggregation. The bacterium Aggregatibacter actinomycetemcomitans and hyperresponsive neutrophils are frequently observed. Antibiotic and nonsurgical therapies are highly effective. Conclusions LAgP differs in many ways from the far more common CP that affects older adults. The substantial evidence of dissimilarities summarized in this review strongly supports the classification of LAgP as a distinct form of periodontitis. Practical Implications Classifying LAgP as a distinct subcategory of periodontitis will encourage future research and does not conflict with the newly proposed “staging and grading” system. The silent onset and rapid progression of LAgP make early diagnosis and frequent follow-up with patients essential for effective treatment.

Skeletal ciliopathies (e.g. Jeune syndrome, short rib polydactyly syndrome, Sensenbrenner syndrome) are frequently associated with cystic kidney disease and other organ manifestations, but a common molecular mechanism has remained elusive.We established two models for skeletal ciliopathies (ift80andift172) inXenopus tropicalis, which exhibited severe limb deformities, polydactyly, cystic kidneys, and ciliogenesis defects, closely matching the phenotype of affected patients.Employing data-mining and anin silicoscreen we identified candidate genes with similar molecular properties to genetically validated skeletal ciliopathy genes. Among four genes experimentally validated, CRISPR/Cas9 targeting ofttc30areplicated all aspects of the phenotypes observed in the models of genetically confirmed disease genes, including ciliary defects, limb deformations and cystic kidney disease.Our findings establish three new models for skeletal ciliopathies (ift80,ift172,ttc30a) and identify TTC30A/B as an essential node in the network of ciliary chondrodysplasia and nephronophthisis-like disease proteins implicating post-translational tubulin modifications in its pathogenesis.

International audience; This paper presents a study on electron field emission (FE) into ultrahigh vacuum (UHV) from a single, cleaned, graphene sheet where its single sheet nature has been carefully characterized and the emission zones are unambiguously the sheet edges. This definitive approach is in contrast to almost all other studies in the literature and can now guide theoretical work and applications. Our sample characterization starts with transmission electron microcopy imaging, Raman characterization, controlled mounting of individual flakes in a scanning electron microscope followed by in situ high temperature and high field treatments. Detailed FE characterization was carried out including current-voltage plots, FE microscopy, and electron energy spectroscopy during subsequent stages of sample cleaning, at room and liquid air temperatures. The full width at half maximum (FWHM) of the energy peak as well as its relative shift versus current and voltage were explored. A notable result is that the energy spectra are very narrow, ten times less than previously reported.