Variable Phenotypes of Knockin Mice Carrying the M712T Gne Mutation

GNE myopathy is a recessive adult onset, slowly progressive distal and proximal myopathy, caused by mutations in the GNE gene. The most frequent mutation in GNE myopathy patients is the Middle Eastern founder mutation M712T. We have generated Gne ^M712T/M712T knockin mice. A high mortality rate in the first generation due to renal failure was recorded (as previously described). However, the following Gne ^M712T/M712T offspring generations could be classified into 3 phenotypic categories: severe, mild and without apparent phenotype. By further crossing between mice with no apparent phenotype, we were able to establish a colony of Gne ^M712T/M712T knockin mice with a high- and long-term survival rate, lacking any renal phenotype. These mice did not present any muscle phenotype (clinical or pathological) for up to 18 months. No correlation was found between the expression of any of the two mRNA Gne isoforms in muscle and the mouse genotype or phenotype. However, the expression of isoform 2 mRNA was significantly higher in the kidney of Gne ^M712T/M712T kidney affected mice compared with control. In contrast, the expression of UPR markers Bip, Chop and of the spliced form of XBP1, was upregulated in muscle of Gne ^M712T/M712T mice compared with controls, but was unchanged in the affected kidney. Thus, Gne defects can affect both muscle and kidney in mouse, but probably through different mechanisms.     

Outcomes of graciloplasty in the treatment of fecal incontinence: a systematic review and meta-analysis of the literature

Techniques in Coloproctology - Patients with refractory fecal incontinence symptoms can be treated with several surgical procedures including graciloplasty. Reported outcomes and morbidity rates of...     

A structured group intervention for siblings of children with cancer

The current study describes the development and evaluation of a structured group intervention for school-aged and adolescent siblings of childhood cancer patients. Twenty-three siblings participated in a six-week program in which parallel groups of younger (ages 7–11) and older (ages 12–17) siblings were conducted. Defined topics were selected from the clinical and research literature and on the basis of a pre-intervention survey, and were addressed at each session. Methods included facilitated group discussion, art therapy techniques, role playing, and informal social interaction. Pre- and postmeasures of cancer-related knowledge, feelings and attitudes towards cancer, and overall mood state were administered. Results indicated statistically and clinically significant improvements in interpersonal problems, intrapsychic preoccupation, disease-related communication, mood, and cancer-related knowledge. Consent and attendance rates, as well as post-intervention satisfaction ratings highlight the subjective need felt by siblings and parents for direct, focused work with this population. Salient issues for siblings of pediatric cancer patients, specific techniques, group dynamics and processes, and staff and parent responses to the intervention program are discussed. The need for replicable, empirically validated interventions for family members of seriously-ill children is emphasized.     

The Autism Diagnostic Interview-Revised and the Childhood Autism Rating Scale: Differences Between Diagnostic Systems and Comparison Between Genders

Diagnoses for autism based on the Autism Diagnostic Interview-Revised (ADI-R) and the Childhood Autism Rating Scale (CARS) were examined for 83 individuals with suspected autism. Agreement between systems reached 85.7%. Participants receiving diagnosis of autism based on only one system were significantly younger in age than individuals receiving diagnoses according to both systems. Individuals who did not receive diagnosis of autism on the ADI-R had lower chronological and mental ages and lower CARS scores compared to individuals who received diagnosis of autism based on the ADI-R. Eighteen females and 18 males were matched to examine possible gender differences. No significant findings were revealed, suggesting that the symptoms of autism according to the ADI-R and CARS do not differ between males and females when matched for chronological and mental ages.     

Recombinant mapping of the familial hyperinsulinism gene to an 0.8 cM region on chromosome 11p15.1 and demonstration of a founder effect in Ashkenazi Jews

A gene for autosomal recessive familial hyperinsulinism (HI)(OMIM: 256450 [OMIM] ), a neonatal metabolic disease characterized byinappropriate insulin secretion In the presence of severe hypoglycemia,was recently mapped to a 6.6 cM interval between the markersD11S926 and D11S928 on chromosome lip In 15 families (1). inthe current study we evaluated six additional families and fivenew markers, and further localized the gene between D11S419and D11S131O. Using genotype data from CEPH Version 7 and datagenerated from this study, this region was estimated to be 0.8cM in length. Significant linkage disequilib rium between markersand the HI gene was observed over a region of 10.3 cM (11pter-D11S926-D11S1308-11pcen)for Ashkenazi Jewish chromosomes. Haplotype analysis showedthat 12 of 36 HI chromosomes, versus one of 36 non-HI chromosomes, bore a specific haplotype for D11S419-D11 S902-D11 S921(p<0.0007), strongly suggesting a founder eftect In thisethnic group.     

The impact of intracoronary thrombus aspiration on STEMI outcomes

BackgroundManual coronary thrombus aspiration was associated with improved outcomes of ST-elevation myocardial infarction (STEMI) patients. We aimed to evaluate the outcome of aspiration in a “real-world” setting of primary percutaneous coronary intervention (PPCI).Methods and materialsWe analyzed the outcome of STEMI patients who underwent PPCI (initial Thrombolysis in Myocardial Infarction flow grade 0/1), comparing patients who underwent aspiration (ASP) to those who had standard (STD) therapy. Various subgroups outcomes were further analyzed. Clinical end points included mortality and major adverse cardiovascular events (MACE) at 30 days and at 1 year.ResultsOne thousand thirty-five consecutive patients were included: 189 (18.26%) with ASP and 846 (81.74%) with STD. ASP patients were younger (58±12 vs. 61±13, P<.05) and had higher incidence of direct stenting compared to STD patients (34% vs. 16.7%, P<.05). No significant differences were noted in the outcome of ASP vs. STD at 30 days (mortality rate 4.2% vs. 4.5%, P=.9; MACE 6.9% vs. 9.8%, P=.2) and at 1 year (mortality rate 8.0% vs. 8.3%, P=.9; MACE 20.0% vs. 22.3%, P=.5). A significant advantage in favor of ASP was evident in patients with proximal culprit lesions, anterior infarcts, and right ventricular involvement.ConclusionsAlthough this was largely a negative study, when STEMI involved a large jeopardized myocardium, aspiration was associated with sustained improved clinical outcomes.