The effect of changes in perilymphatic K+ on the vestibular evoked potential in the guinea pig

To investigate the effect on the functioning of the vestibular system of a rupture of Reissner’s membrane, artificial endolymph was injected in scala media of ten guinea pigs and vestibular evoked potentials (VsEPs), evoked by vertical acceleration pulses, were measured. Directly after injection of a sufficient volume to cause rupture, all ears showed a complete disappearance of VsEP, followed by partial recovery. To investigate the effect of perilymphatic potassium concentration on the vestibular sensory and neural structures, different concentrations of KCl were injected directly into the vestibule. The KCl injections resulted in a dose-dependent decrease of VsEP, followed by a dose-dependent slow recovery. This animal model clearly shows a disturbing effect of a higher than normal K+ concentration in perilymph on the vestibular and neural structures in the inner ear. Potassium intoxication is the most probable explanation for the observed effects. It is one of the explanations for Menière attacks

Territori di confine. La relazione con soggetti affetti da patologie neuropsichiatriche e il valore terapeutico dell'arte.

Analisi della relazione con soggetti affetti da patologie neuropsichiatriche e uso dell'arte come terapia. L'elaborato inizia considerando la relazione fra uomo, società e cultura. Dopo aver chiarito cosa si intenda per cultura, vengono prese in esame le forme artistiche di musica, teatro e scrittura evidenziandone le caratteristiche propriamente pedagogiche. Queste tre forme verranno riportate nella trattazione come mezzi per la cura e la valorizzazione di soggetti affetti da malattia di Alzheimer, patologie psichiatriche e disabilità intellettive. Il lavoro si conclude con un'analisi specifica sulla musicoterapia

Associations between lifestyle factors and an unhealthy diet

BACKGROUND: Unhealthy dietary patterns have been associated with other unhealthy lifestyle factors such as smoking and physical inactivity. Whether these associations are similar in high- and low-educated individuals is currently unknown. METHODS: We used information of the EPIC-NL cohort, a prospective cohort of 39 393 men and women, aged 20-70 years at recruitment. A lifestyle questionnaire and a validated food frequency questionnaire were administered at recruitment (1993-97). Low adherence to a Mediterranean-style diet was used to determine an unhealthy dietary pattern. Lifestyle-related factors included body mass index, waist circumference, smoking status, physical activity level, dietary supplement use and daily breakfast consumption. Multivariate logistic regression analyses were performed for the total population and by strata of educational level. RESULTS: In total 30% of the study population had an unhealthy dietary pattern: 39% in the lowest educated group and 20% in the highest educated group. Physical inactivity, a large waist circumference, no dietary supplement use and skipping breakfast were associated with an unhealthy dietary pattern in both low and high educated participants. Among low educated participants, current smokers had a greater odds of an unhealthy diet compared with never smokers: OR 1.42 (95% CI: 1.25; 1.61). This association was not observed in the high educated group. CONCLUSIONS: Most associations between lifestyle-related factors and unhealthy diet were consistent across educational levels, except for smoking. Only among low educated participants, current smokers reported an unhealthier dietary pattern in comparison to never smokers. These results can be used in the development of targeted health promotion strategies

Supersymmetric Vacua in Random Supergravity

We determine the spectrum of scalar masses in a supersymmetric vacuum of a general N=1 supergravity theory, with the Kahler potential and superpotential taken to be random functions of N complex scalar fields. We derive a random matrix model for the Hessian matrix and compute the eigenvalue spectrum. Tachyons consistent with the Breitenlohner-Freedman bound are generically present, and although these tachyons cannot destabilize the supersymmetric vacuum, they do influence the likelihood of the existence of an `uplift' to a metastable vacuum with positive cosmological constant. We show that the probability that a supersymmetric AdS vacuum has no tachyons is formally equivalent to the probability of a large fluctuation of the smallest eigenvalue of a certain real Wishart matrix. For normally-distributed matrix entries and any N, this probability is given exactly by P = exp(-2N^2|W|^2/m_{susy}^2), with W denoting the superpotential and m_{susy} the supersymmetric mass scale; for more general distributions of the entries, our result is accurate when N >> 1. We conclude that for |W| \gtrsim m_{susy}/N, tachyonic instabilities are ubiquitous in configurations obtained by uplifting supersymmetric vacua.Comment: 26 pages, 6 figure

General Aspects of Tree Level Gauge Mediation

Tree level gauge mediation (TGM) may be considered as the simplest way to communicate supersymmetry breaking: through the tree level renormalizable exchange of heavy gauge messengers. We study its general structure, in particular the general form of tree level sfermion masses and of one loop, but enhanced, gaugino masses. This allows us to set up general guidelines for model building and to identify the hypotheses underlying the phenomenological predictions. In the context of models based on the "minimal" gauge group SO(10), we show that only two "pure" embeddings of the MSSM fields are possible using $d< 120$ representations, each of them leading to specific predictions for the ratios of family universal sfermion masses at the GUT scale, $m^2_{\bar{5}} = 2 m^2_{10}$ or $m^2_{\bar{5}} = (3/4) m^2_{10}$ (in SU(5) notation). These ratios are determined by group factors and are peculiar enough to make this scheme testable at the LHC. We also discuss three possible approaches to the $\mu$-problem, one of them distinctive of TGM.Comment: 37 pages, 2 figure

Tone burst-evoked otoacoustic emissions in neonates: normative data

<p>Abstract</p> <p>Background</p> <p>Tone-burst otoacoustic emissions (TBOAEs) have not been routinely studied in pediatric populations, although tone burst stimuli have greater frequency specificity compared with click sound stimuli. The present study aimed (1) to determine an appropriate stimulus level for neonatal TBOAE measurements when the stimulus center frequency was 1 kHz, (2) to explore the characteristics of 1 kHz TBOAEs in a neonatal population.</p> <p>Methods</p> <p>A total of 395 normal neonates (745 ears) were recruited. The study consisted of two parts, reflecting the two study aims. Part I included 40 normal neonatal ears, and TBOAE measurement was performed at five stimulus levels in the range 60–80 dB peSPL, with 5 dB incremental steps. Part II investigated the characteristics of the 1 kHz TBOAE response in a large group of 705 neonatal ears, and provided clinical reference criteria based on these characteristics.</p> <p>Results</p> <p>The study provided a series of reference parameters for 1 kHz TBOAE measurement in neonates. Based on the results, a suggested stimulus level and reference criteria for 1 kHz TBOAE measures with neonates were established. In addition, time-frequency analysis of the data gave new insight into the energy distribution of the neonatal TBOAE response.</p> <p>Conclusion</p> <p>TBOAE measures may be a useful method for investigating cochlear function at specific frequency ranges in neonates. However, further studies of both TBOAE time-frequency analysis and measurements in newborns are needed.</p

Wolcott-Rallison syndrome

Wolcott-Rallison syndrome (WRS) is a rare autosomal recessive disease, characterized by neonatal/early-onset non-autoimmune insulin-requiring diabetes associated with skeletal dysplasia and growth retardation. Fewer than 60 cases have been described in the literature, although WRS is now recognised as the most frequent cause of neonatal/early-onset diabetes in patients with consanguineous parents. Typically, diabetes occurs before six months of age, and skeletal dysplasia is diagnosed within the first year or two of life. Other manifestations vary between patients in their nature and severity and include frequent episodes of acute liver failure, renal dysfunction, exocrine pancreas insufficiency, intellectual deficit, hypothyroidism, neutropenia and recurrent infections. Bone fractures may be frequent. WRS is caused by mutations in the gene encoding eukaryotic translation initiation factor 2α kinase 3 (EIF2AK3), also known as PKR-like endoplasmic reticulum kinase (PERK). PERK is an endoplasmic reticulum (ER) transmembrane protein, which plays a key role in translation control during the unfolded protein response. ER dysfunction is central to the disease processes. The disease variability appears to be independent of the nature of the EIF2AK3 mutations, with the possible exception of an older age at onset; other factors may include other genes, exposure to environmental factors and disease management. WRS should be suspected in any infant who presents with permanent neonatal diabetes associated with skeletal dysplasia and/or episodes of acute liver failure. Molecular genetic testing confirms the diagnosis. Early diagnosis is recommended, in order to ensure rapid intervention for episodes of hepatic failure, which is the most life threatening complication. WRS should be differentiated from other forms of neonatal/early-onset insulin-dependent diabetes based on clinical presentation and genetic testing. Genetic counselling and antenatal diagnosis is recommended for parents of a WRS patient with confirmed EIF2AK3 mutation. Close therapeutic monitoring of diabetes and treatment with an insulin pump are recommended because of the risk of acute episodes of hypoglycaemia and ketoacidosis. Interventions under general anaesthesia increase the risk of acute aggravation, because of the toxicity of anaesthetics, and should be avoided. Prognosis is poor and most patients die at a young age. Intervention strategies targeting ER dysfunction provide hope for future therapy and prevention

Incidence and risk factors for community-acquired acute gastroenteritis in north-west Germany in 2004

In developed countries, acute gastroenteritis (AGE) is a major source of morbidity. However, only a few studies have estimated its incidence and the associated medical burden. This population-based study determined the incidence of community-acquired AGE patients seeking medical care and the relative role of various pathogens. Stool samples from patients with AGE presenting to a general practitioner (GP), pediatrician, or specialist in internal medicine for that reason were screened for various bacterial and viral enteropathogens. A control group was established as well. Incidences were calculated by the number of positive patients divided by the general population. The study was performed in north-west Germany in 2004. The incidence of AGE patients requiring medical consultation was 4,020/100,000 inhabitants. Children (<5 years of age) were at the highest risk (13,810/100,000 inhabitants). Of the patients, 6.6% were tested positive for an enteropathogenic bacteria and 17.7% for a viral agent. The predominant pathogens were norovirus (626/100,000) and rotavirus (270/100,000). Salmonella was the most frequently detected bacteria (162/100,000). The results presented confirm AGE and, specifically, AGE of viral origin as a major public health burden in developed countries

Storage of Factor VIII Variants with Impaired von Willebrand Factor Binding in Weibel-Palade Bodies in Endothelial Cells

BACKGROUND: Point mutations resulting in reduced factor VIII (FVIII) binding to von Willebrand factor (VWF) are an important cause of mild/moderate hemophilia A. Treatment includes desmopressin infusion, which concomitantly increases VWF and FVIII plasma levels, apparently from storage pools containing both proteins. The source of these VWF/FVIII co-storage pools and the mechanism of granule biogenesis are not fully understood. METHODOLOGY/PRINCIPAL FINDINGS: We studied intracellular trafficking of FVIII variants implicated in mild/moderate hemophilia A together with VWF in HEK293 cells and primary endothelial cells. The role of VWF binding was addressed using FVIII variants displaying reduced VWF interaction. Binding studies using purified FVIII proteins revealed moderate (Arg2150His, Del2201, Pro2300Ser) to severe (Tyr1680Phe, Ser2119Tyr) VWF binding defects. Expression studies in HEK293 cells and primary endothelial cells revealed that all FVIII variants were present within VWF-containing organelles. Quantitative studies showed that the relative amount of FVIII storage was independent of various mutations. Substantial amounts of FVIII variants are co-stored in VWF-containing storage organelles, presumably by virtue of their ability to interact with VWF at low pH. CONCLUSIONS: Our data suggest that the potential of FVIII co-storage with VWF is not affected in mild/moderate hemophilia A caused by reduced FVIII/VWF interaction in the circulation. These data support the hypothesis that Weibel-Palade bodies comprise the desmopressin-releasable FVIII storage pool in vivo