No effect of oral sucrose or IV glucose during exercise in phosphorylase b kinase deficiency.

This case report investigated exercise metabolism and the effect of oral sucrose and intravenous glucose supplementation in a 30-year-old, mildly affected man with muscle phosphorylase b kinase (PHK) deficiency caused by a novel c.586G>A mutation in the PHKA1 gene. Only 12 patients with PHK deficiency have been reported and it is unclear to what extent patients exhibit symptoms during exercise. Carbohydrate and fat metabolism were measured during 30 min of exercise at ∼ 70% of peak oxidative capacity using stabile isotope technique and signaling proteins and enzymes in the energy pathway were analyzed by Western blot. Results were compared to four healthy subjects. These studies show that neither oral nor intravenous glucose improved exercise tolerance in this patient with PHK deficiency. Despite Western blots indicated affected metabolism on protein level, systemic substrate turnover studies showed that carbohydrate and fatty acid oxidations were normal.

[Inadequate ICU-admissions : A 12-month prospective cohort study at a German University Hospital]. / Nicht indizierte Aufnahmen auf der Intensivstation : 12-Monats-Observationsstudie an einem Universitätsklinikum.

BACKGROUND: Intensive care medicine (ICM) is increasingly utilized by a growing number of critically ill patients worldwide. The reasons for this are an increasingly ageing and multimorbid population and technological improvements in ICM. Inappropriate patient admissions to the intensive care unit (ICU) can be a threat to rational resource allocation and to patient autonomy. OBJECTIVES: In this study, the incidence, characteristics, and resource utilization of patients inappropriately admitted to ICUs are studied. METHODS: This prospective study included all consecutive patients admitted from 01 September 2012 to 31 August 2013 to the Department of Intensive Care Medicine of a German university hospital comprised of 10 ICUs and 120 beds. Inappropriate admission was defined according to category 4B of the recommendations of the Society of Critical Care Medicine (SCCM; "futility of ICU treatment" or "ICU declined by patient") and was determined in each suspected case by structured group discussions between the study team and all involved care givers including the referring team. RESULTS: In all, 66 of 6452 ICU admissions (1 %) were suspected to have been inappropriate on retrospective evaluation the day after admission. In 50 patients (0.8 %), an interdisciplinary consensus was reached on the inappropriateness of the ICU admission. Of these 50 patients, 41 (82 %) had previously declined ICU treatment in principle. This information was based on the patient's presumed wish as expressed by next of kin (56 %) or in a written advanced directive (26 %). In 9 patients (18 %), ICU treatment was considered futile. In all cases, a lack of information regarding a patient's wishes or clinical prognosis was the reason for inappropriate ICU admission. CONCLUSION: In this study, patients were regularly admitted to the ICU despite their contrary wish/directive or an unfavorable clinical condition. Although this was registered in only 1 % of all admissions, optimizing preICU admission information flow with regard to relevant exclusion criteria not only helps respect patient autonomy but also allows for more adequate resource allocation.

Phosphorylation-independent interaction between 14-3-3 protein and the plant plasma membrane H+-ATPase.

14-3-3 proteins interact with a novel phosphothreonine motif (Y(946)pTV) at the extreme C-terminal end of the plant plasma membrane H(+)-ATPase molecule. Phosphorylation-independent binding of 14-3-3 protein to the YTV motif can be induced by the fungal phytotoxin fusicoccin. The molecular basis for the phosphorylation-independent interaction between 14-3-3 and H(+)-ATPase in the presence of fusicoccin has been investigated in more detail. Fusicoccin binds to a heteromeric receptor that involves both 14-3-3 protein and H(+)-ATPase. Binding of fusicoccin is dependent upon the YTV motif in the H(+)-ATPase and, in addition, requires residues further upstream of this motif. Apparently, 14-3-3 proteins interact with the unusual epitope in H(+)-ATPase via its conserved amphipathic groove. This implies that very diverse epitopes bind to a common structure in the 14-3-3 protein.

14-3-3 proteins: eukaryotic regulatory proteins with many functions.

The enigmatically named 14-3-3 proteins have been the subject of considerable attention in recent years since they have been implicated in the regulation of diverse physiological processes, in eukaryotes ranging from slime moulds to higher plants. In plants they have roles in the regulation of the plasma membrane H+-ATPase and nitrate reductase, among others. Regulation of target proteins is achieved through binding of 14-3-3 to short, often phosphorylated motifs in the target, resulting either in its activation (e.g. H+-ATPase), inactivation (e.g. nitrate reductase) or translocation (although this function of 14-3-3 proteins has yet to be demonstrated in plants). The native 14-3-3 proteins are homo- or heterodimers and, as each monomer has a binding site, a dimer can potentially bind two targets, promoting their association. Alternatively, target proteins may have more than one 14-3-3-binding site. In this mini review, we present a synthesis of recent results from plant 14-3-3 research and, with reference to known 14-3-3-binding motifs, suggest further subjects for research.

Etiologic factors in secretory otitis.

We investigated the possible etiologic factors of secretory otitis and dysfunction of the Eustachian tube in 278 healthy 2-year-old children based on screening tympanometry and medical history. We found that catarrhalia was the most frequent etiologic factor, with acute otitis being the second most frequent factor. It was demonstrated that secretory otitis may develop without a preceding infection of the middle ear. It is probable that dysfunction of the tube plays a primary role in the development of secretory otitis. Allergy did not seem to be an etiologic factor. Antibiotic treatment does not promote the development of secretory otitis, but is probably unable to prevent it. Parental disposition could not be related to the children's ear diseases.

Tympanometry in 2-year-old children.

Screening tympanometry was performed in 278 healthy 2-year-old children (556 ears) born the first 10 days of every month in 1976 in two municipalities from Copenhagen County. A middle ear pressure between 0 and -99 mm H2O was found in 49.6%, between -100 and -199 in 19.4%, between -200 and -300 in 20.1%, and flat curves in 10.8%. The latter group also otoscopically gave evidence of middle ear effusion. The results reveal the highest incidence of tubal dysfunction and middle ear effusion for this age group in contrast to any other age group. However, a large spontaneous recovery from secretory otitis was also noted. No differences were found between sexes, right ear/left ear, the socio-economic factors, or whether the children lived in houses or apartments. Children who were nursed in public nurseries had a significantly higher incidence of secretory otitis than those nursed in private nurseries or at home.