Photoresponsive New Polysiloxanes with 4‐Substituted Azobenzene Side‐Groups. Synthesis,Characterization and Kinetics of the Reversible Trans‐Cis‐Trans Isomerization

New polydimethylsiloxanes with p‐substituted azobenzene side‐groups were synthesized. Thin films and solutions exhibit a photochemical trans‐cis isomerization of the azobenzene groups, followed by their cis‐trans thermal relaxation in the dark. In films, relaxation rates were found to be 100–1 000 times slower than the rates of photoisomerization, the former being very sensitive to the electron‐acceptor character of the substituents. in solution, the rates of cis‐trans relaxation are lower than those obtained for the solid state. This is ascribed to the dipolar intramolecular interactions between cis chromophores, which are favored in solution.

     

A genome scan in 260 inflammatory bowel disease-affected relative pairs

We report genome-wide linkage results using model-free linkage analysis (Allegro) of 358 autosomal microsatellites in 260 new inflammatory bowel disease-affected relative pairs from 139 Caucasian families, including 108 Crohn's disease-affected relative pairs and 72 ulcerative colitis-affected relative pairs. Our results provide confirmatory evidence for linkage between the IBD2 locus and the inflammatory bowel disease phenotype (lod = 2.12 at GATA91H06) and ulcerative colitis phenotype (lod = 1.44 at GATA91H06), but not the Crohn's disease phenotype. We also find confirmatory evidence for linkage between the IBD3 locus and Crohn's disease (lod = 2.26 at D6S2439) but not ulcerative colitis or inflammatory bowel disease. We find nominal evidence for linkage of inflammatory bowel disease to loci on chromosome 6q (lod = 2.21 between D6S2436/D6S305), 8q (lod = 1.57 between D8S1113/D8S1136), 15q (lod = 2.02 between D15S652/D15S816), and 22 (lod = 1.50 at D22S689); of Crohn's disease to loci on chromosome 5q approximately 50 centiMorgans centromeric from IBD5 (lod = 1.69 at D5S1501) and 15q (lod = 1.82 at D15S652); and of ulcerative colitis to a locus on chromosome 2q (lod = 2.19 between D2S1776/D2S1391). The inflammatory bowel disease linkage peak on chromosome 6q is located in the same general region that showed nominal evidence for linkage to IBD in a Belgian genome scan, and the ulcerative colitis linkage peak on chromosome 2q is located in the same general region that showed nominal evidence for linkage to the inflammatory bowel disease, Crohn's disease, or ulcerative colitis phenotypes in four other European/North American genome scans.     

Dynamic MR imaging of outlet obstruction

The outlet obstruction syndrome encompasses all pelvic floor abnormalities which are responsible for an incomplete evacuation of fecal contents from the rectum. It has been estimated that outlet obstruction may be observed in half of constipated patients. A detailed clinical examination still represents the cornerstone of the diagnosis of these patients. However, there is general agreement that a reliable evaluation of the different pelvic floor abnormalities and the treatment decision highly depend on the imaging assessment. Traditionally, conventional defecography has played an important role in the radiological assessment of these patients but the technique is limited by its projectional nature and its inability to detect soft-tissue structures. Dynamic pelvic MR imaging using either closed-configuration or open-configuration MR systems is a rapidly evolving technique which has been gaining increased interest over the last years. The free selection of imaging planes, the good temporal resolution, and the excellent soft-tissue contrast have transformed this method into the preferred imaging modality in the evaluation of patients with pelvic floor dysfunction including rectocele, enterocele, internal rectal prolapse, and anismus.     

Changes in arterial stiffness following dialysis in relation to overhydration and to endothelial function

Introduction

Cardiovascular (CV) morbidity and mortality are greatly enhanced in patients with chronic kidney disease, partly due to increased arterial stiffness.

Material and method

The study included 63 stable HD patients. Stiffness parameters were evaluated by applanation tonometry before the mid-week HD sessions. Pre-HD bioimpedance parameters were measured. A phase angle <six degrees was previously reported as abnormal, reflecting extracellular overhydration. Fluid status was evaluated echocardiographic by measuring the inferior vena cava (IVC) diameter. Endothelium-dependent and endothelium-independent vascular reactivity were assessed by changes in Alx following sublingual nitroglycerin and inhaled salbutamol.

Results

PWV directly correlated with patients?? age and dialysis vintage. Patients with a phase angle <6°, were significantly overhydrated (larger IVC, increased ECW, and lower ICW), had stiffer arteries and greater left ventricle mass (LVM), compared with those with a phase angle >6°. Overhydration increases arterial stiffness, but has no influence on either EID or ED vascular reactivity.

Conclusion

In hemodialysis, volume overload is an important contributor to increased arterial stiffness and modifies cardiovascular status especially by LV hypertrophy. Achieving normohydration may significantly ameliorate cardiac abnormalities and arterial stiffness and may impact major clinical events and CV mortality.     

Structural basis for dynamic mechanism of proton-coupled symport by the peptide transporter POT

Proton-dependent oligopeptide transporters (POTs) are major facilitator superfamily (MFS) proteins that mediate the uptake of peptides and peptide-like molecules, using the inwardly directed H⁺ gradient across the membrane. The human POT family transporter peptide transporter 1 is present in the brush border membrane of the small intestine and is involved in the uptake of nutrient peptides and drug molecules such as β-lactam antibiotics. Although previous studies have provided insight into the overall structure of the POT family transporters, the question of how transport is coupled to both peptide and H⁺ binding remains unanswered. Here we report the high-resolution crystal structures of a bacterial POT family transporter, including its complex with a dipeptide analog, alafosfalin. These structures revealed the key mechanistic and functional roles for a conserved glutamate residue (Glu310) in the peptide binding site. Integrated structural, biochemical, and computational analyses suggested a mechanism for H⁺-coupled peptide symport in which protonated Glu310 first binds the carboxyl group of the peptide substrate. The deprotonation of Glu310 in the inward open state triggers the release of the bound peptide toward the intracellular space and salt bridge formation between Glu310 and Arg43 to induce the state transition to the occluded conformation.     

The Telegraph nail for proximal humeral fractures: a prospective four-year study

Proximal humeral fractures in 67 patients older than 50 years treated with the Telegraph nail (FH Orthopedics, Heimsbrunn, France) were monitored for 4 years to assess the fracture pattern (weighted Constant score), ranges of motion, and patient satisfaction. The outcome was best in patients with extraarticular surgical neck fractures (mean weighted Constant score, 93.5%); scores were 85% and 77.5%, respectively, for valgus impacted fractures and intraarticular displaced or dislocated fractures. Some or all of the hardware was removed in 21 patients (31%). Two required implant removed for mechanical problems related to screw positioning or migration; 8 were revised because proximal migration of the implant resulted in subacromial impingement. Avascular necrosis occurred in 18% of valgus impacted fractures and in 37.5% of displaced articular or dislocated fractures. Secondary migration of the tuberosities occurred in 6 (all 4-part fractures). The Telegraph nail provides a reproducible and satisfactory outcome for surgical neck and valgus impacted fractures in older patients. The outcome was less satisfactory for unstable articular or dislocated fractures.     

Quantifying the amount of missing information in genetic association studies

Many genetic analyses are done with incomplete information; for example, unknown phase in haplotype-based association studies. Measures of the amount of available information can be used for efficient planning of studies and/or analyses. In particular, the linkage disequilibrium (LD) between two sets of markers can be interpreted as the amount of information one set of markers contains for testing allele frequency differences in the second set, and measuring LD can be viewed as quantifying information in a missing data problem. We introduce a framework for measuring the association between two sets of variables; for example, genotype data for two distinct groups of markers, or haplotype and genotype data for a given set of polymorphisms. The goal is to quantify how much information is in one data set, e.g. genotype data for a set of SNPs, for estimating parameters that are functions of frequencies in the second data set, e.g. haplotype frequencies, relative to the ideal case of actually observing the complete data, e.g. haplotypes. In the case of genotype data on two mutually exclusive sets of markers, the measure determines the amount of multi-locus LD, and is equal to the classical measure r(2), if the sets consist each of one bi-allelic marker. In general, the measures are interpreted as the asymptotic ratio of sample sizes necessary to achieve the same power in case-control testing. The focus of this paper is on case-control allele/haplotype tests, but the framework can be extended easily to other settings like regressing quantitative traits on allele/haplotype counts, or tests on genotypes or diplotypes. We highlight applications of the approach, including tools for navigating the HapMap database [The International HapMap Consortium, 2003], and genotyping strategies for positional cloning studies.     

Clostridium difficile infections: what is new?

C. difficile is the most common infectious cause of healthcare-associated diarrhea but now is increasingly recognized as a cause of diarrhea in outpatients and persons without apparent health care contacts. Emergence and spread of new epidemic clones of C. difficile 027 (PCR-ribotype) and 078/126 (toxinotype) with increase toxin production, an aditional binary toxin and high level resistance to fluoroquinolones and increasing incidence of more rapidly progressive severe disease, require prompt clinical recognition and new tools to predict severity and to prevent recurrences. Although antibiotics are effective at inhibiting C. difficile and treating symptoms, these drugs could not reestablish normal bowel flora and the rate of recurrences is 25%. During the past years we assisted to an impressive search for new and more effective therapy that shoud be save, with low potential for the development of resistance, with low levels of systemic absorbtion and high levels of active drug in the colon and should be associated with a low rate of recurrence after treatment. By consequence, different approaches to the management of recurrent infections have been studied such as new antibiotics (fidaxomicin), human monoclonal antibodies against C. difficile toxins A and B, intravenous human immunoglobulin, active immunization, and probiotic therapy.