Overweight and obesity in children: known facts and new trends

The prevalence of overweight and obesity in children is increasing. A growing number of children are thus suffering from complications of obesity. Contributing factors can be found on an individual level as well as in the familial and social environment of affected children. Currently there is no single evidence-based treatment strategy available. Studies from family practice are scarce. Multimodal, long-term, easily accessible treatments as offered in family practice are promising and likely to be cost-effective. The sustainability of these changes in behavior still needs to be demonstrated.

'New perspectives on well-known issues': patients' experiences and perceptions of safety in Swiss hospitals

Patients' reports of safety-related events and perceptions of safety can be a valuable source for hospitals. Patients of eight acute care hospitals in Switzerland were surveyed for safety-related events and concerns for safety. In workshops with hospitals areas for improvement were analyzed and priorities for change identified. To evaluate the benefit of the approach, semi-structured interviews were conducted with hospital risk managers. 3,983 patients returned the survey (55% response rate). 21.4% reported at least one definite safety event, and the mean number of 'definite' incidents per patient was 0.31 (95% CI=0.29 to 0.34). 3.2% were very concerned and 14.7% were somewhat concerned about medical errors and safety. Having experienced a safety-related event, younger age, length of stay, poor health and a poor education increased the probability of reporting concerns. With some exceptions, results confirmed the hospitals' a priori expectations regarding the strengths and weaknesses of their institutions. Risk managers emphasized the usability of results for their work and the special value of referring to the patient's perspective at their home institutions. A considerable fraction of patients subjectively experiences safety-related events and is concerned about safety. Patient-generated data introduced a new quality into the discussion of safety issues within hospitals, and some expected that patients' experiences and concerns could affect patient volumes. Though the study is limited by the short time horizon and the lack of follow-up, the results suggest that the described approach is feasible and can serve as a supplemental tool for risk identification and management.

Interhemispheric connections shape subjective experience of bistable motion

The right and left visual hemifields are represented in different cerebral hemispheres and are bound together by connections through the corpus callosum. Much has been learned on the functions of these connections from split-brain patients [1-4], but little is known about their contribution to conscious visual perception in healthy humans. We used diffusion tensor imaging and functional magnetic resonance imaging to investigate which callosal connections contribute to the subjective experience of a visual motion stimulus that requires interhemispheric integration. The "motion quartet" is an ambiguous version of apparent motion that leads to perceptions of either horizontal or vertical motion [5]. Interestingly, observers are more likely to perceive vertical than horizontal motion when the stimulus is presented centrally in the visual field [6]. This asymmetry has been attributed to the fact that, with central fixation, perception of horizontal motion requires integration across hemispheres whereas perception of vertical motion requires only intrahemispheric processing [7]. We are able to show that the microstructure of individually tracked callosal segments connecting motion-sensitive areas of the human MT/V5 complex (hMT/V5+; [8]) can predict the conscious perception of observers. Neither connections between primary visual cortex (V1) nor other surrounding callosal regions exhibit a similar relationship.

[Geneva, France, pharmacist. An outline on a little-known French-Genovoise pharmacopoeia]

In the time of the French occupation of Geneva and the formation of a << Départment du Léman >> from 1798 to 1813, the physician Louis Odier published a Manual of practical medicine destined for the Health officers of the Departement. This work encloses at its end a short pharmacopoeia, till today practically unknown in the pharmaceutical bibliography, which is described here. An analysis shows that this formulary does not belong to the popular literature but is corresponding, with some exceptions, to the other similar pharmacopoeal works of the Enlightenment.

Objective response to radiation therapy and long-term survival of patients with WHO grade II astrocytic gliomas with known LOH 1p/19q status

BACKGROUND: WHO grade II gliomas are often approached by radiation therapy (RT). However, little is known about tumor response and its potential impact on long-term survival. PATIENTS AND METHODS: Patients subjected to RT were selected from the own database of WHO grade II gliomas diagnosed between 1991 and 2000. The volumetric tumor response after RT was assessed based on magnetic resonance imaging and graded according to standard criteria as complete, partial (PR, >or= 50%), or minor (MR, 25% to <50%). RESULTS: There were 24 astrocytomas and three oligoastrocytomas. 21 patients (78%) were dead at follow-up (mean survival 74 months). None of the patients had chemotherapy. Objective response occurred in 14 patients (52%, five PR and nine MR) but was not associated with overall survival. The vast majority of the tumors had no loss of heterozygosity (LOH) 1p and/or 19q (86%). CONCLUSION: Approximately 50% of patients with astrocytic WHO grade II gliomas respond to RT despite the absence of LOH for 1p/19q. The potential predictive factors for response and the impact of response on overall survival remain unclear.

In vitro fracture strength and thermal shock resistance of metal-ceramic crowns with cast and machined AuTi frameworks

STATEMENT OF PROBLEM: AuTi alloys with 1.6% to 1.7% (wt%) Ti provide sufficient bond strength to veneering ceramics, but the strength of entire metal-ceramic restorations fabricated from these alloys is not known. However, this information is important to assess the clinical performance of such materials. PURPOSE: This in vitro study evaluated the fracture strength and thermal shock resistance of metal-ceramic crowns with AuTi frameworks produced by milling or casting. MATERIAL AND METHODS: Frameworks of the alloy Au-1.7Ti-0.1Ir (wt%) (Esteticor Vision) were produced by milling or casting (test groups). A high-gold alloy (Esteticor Special) was used as the control. The frameworks were veneered with ceramic (VMK 95). Specimens (n=7) were loaded until fracture. Loads at failure (N) were recorded and the mean values statistically evaluated using 1-way analysis of variance and a post hoc Dunnett test (alpha=.05). To assess the crazing resistance of the veneering ceramic, 6 additional crowns of each group were subjected to a thermal shock test. Fractured surfaces were documented by scanning electron microscopy. Coefficients of thermal expansion of the materials used were measured (n=2) to assess the thermal compatibility between alloys and ceramic. RESULTS: The mean fracture strength of the crowns with machined AuTi frameworks (1294 +/- 236 N) was significantly lower (P=.012) than that of the cast AuTi frameworks (1680 +/- 150 N), but statistically not different than the high-gold alloy (1449 +/- 159 N). Bonding failure to the AuTi alloy predominantly occurred at the alloy-oxide interface. For the high-gold alloy, more ceramic residues were observed. In the thermal shock test, crowns with milled AuTi frameworks showed significantly higher thermal shock resistance compared to the other groups. The coefficients of thermal expansion (Esteticor Vision cast: 14.5 microm/m.K; Esteticor Vision milled: 14.3 microm/m.K; Esteticor Special cast: 13.7 microm/m.K) did not correlate with the results of the thermal shock test. CONCLUSION: The in vitro fracture strength of crowns with milled AuTi frameworks is lower than that obtained with cast AuTi frameworks, but comparable to those crowns produced with a high-gold alloy.

Predictive value of known and novel alleles of CYP2B6 for efavirenz plasma concentrations in HIV-infected individuals

To assess the association of CYP2B6 allelic diversity with efavirenz (EFV) pharmacokinetics, we performed extensive genotyping of 15 relevant single nucleotide polymorphism in 169 study participants, and full resequencing of CYP2B6 in individuals with abnormal EFV plasma levels. Seventy-seven (45.5%) individuals carried a known (CYP2B6*6, *11, *15, or *18) or new loss/diminished-function alleles. Resequencing defined two new loss-of-function alleles: allele *27 (marked by 593T>C [M198T]), that results in 85% decrease in enzyme activity and allele *28 (marked by 1132C>T), that results in protein truncation at arginine 378. Median AUC levels were 188.5 microg h/ml for individuals homozygous for a loss/diminished-function allele, 58.6 microg h/ml for carriers, and 43.7 microg h/ml for noncarriers (P<0.0001). Individuals with a poor metabolizer genotype had a likelihood ratio of 35 (95% CI, 11-110) of presenting very high EFV plasma levels. CYP2B6 poor metabolizer genotypes explain to a large extent EFV pharmacokinetics and identify individuals at risk of extremely elevated EFV plasma levels.

Little-known Swiss contributions to the description, diagnosis, and surgery of lumbar disc disease before the Mixter and Barr era

The understanding of lumbar spine pathologies made substantial progress at the turn of the twentieth century. The authors review the original publication of Otto Veraguth in 1929 reporting on the successful resection of a herniated lumbar disc, published exclusively in the German language. His early report is put into the historical context, and its impact on the understanding of pathologies of the intervertebral disc (IVD) is estimated. The Swiss surgeon and Nobel Prize laureate Emil Theodor Kocher was among the first physicians to describe the traumatic rupture of the IVD in 1896. As early as 1909 Oppenheim and Krause published 2 case reports on surgery for a herniated lumbar disc. Goldthwait was the first physician to delineate the etiopathogenes is between annulus rupture, symptoms of sciatica, and neurological signs in his publication of 1911. Further publications by Middleton and Teacher in 1911 and Schmorl in 1929 added to the understanding of lumbar spinal pathologies. In 1929, the Swiss neurologist Veraguth (surgery performed by Hans Brun) and the American neurosurgeon Walter Edward Dandy both published their early experiences with the surgical therapy of a herniated lumbar disc. Veraguth's contribution, however, has not been appreciated internationally to date. The causal relationship between lumbar disc pathology and sciatica remained uncertain for some years to come. The causal relationship was not confirmed until Mixter and Barr's landmark paper in 1934 describing the association of sciatica and lumbar disc herniation, after which the surgical treatment became increasingly popular. Veraguth was among the first physicians to report on the clinical course of a patient with successful resection of a herniated lumbar disc. His observations should be acknowledged in view of the limited experience and literature on this ailment at that time.

Design, synthesis and pharmacological characterization of analogs of 2-aminoethyl diphenylborinate (2-APB), a known store-operated calcium channel blocker, for inhibition of TRPV6-mediated calcium transport

2-Aminoethyl diphenylborinate (2-APB) is a known modulator of the IP3 receptor, the calcium ATPase SERCA, the calcium release-activated calcium channel Orai and TRP channels. More recently, it was shown that 2-APB is an efficient inhibitor of the epithelial calcium channel TRPV6 which is overexpressed in prostate cancer. We have conducted a structure-activity relationship study of 2-APB congeners to understand their inhibitory mode of action on TRPV6. Whereas modifying the aminoethyl moiety did not significantly change TRPV6 inhibition, substitution of the phenyl rings of 2-APB did. Our data show that the diaryl borinate moiety is required for biological activity and that the substitution pattern of the aryl rings can influence TRPV6 versus SOCE inhibition. We have also discovered that 2-APB is hydrolyzed and transesterified within minutes in solution.