Assessment of a new undergraduate module in musculoskeletal medicine.

BACKGROUND: Despite the high prevalence of musculoskeletal disorders seen by primary care physicians, numerous studies have demonstrated deficiencies in the adequacy of musculoskeletal education at multiple stages of medical education. The aim of this study was to assess a newly developed module in musculoskeletal medicine for use at European undergraduate level (i.e., the medical-school level). METHODS: A two-week module in musculoskeletal medicine was designed to cover common musculoskeletal disorders that are typically seen in primary care. The module incorporated an integrated approach, including core lectures, bedside clinical examination, and demonstration of basic practical procedures. A previously validated examination in musculoskeletal medicine was used to assess the cognitive knowledge of ninety-two students on completion of the module. A historical control group (seventy-two students) from a prior course was used for comparison. RESULTS: The new module group (2009) performed significantly better than the historical (2006) control group in terms of score (62.3% versus 54.3%, respectively; p \u3c 0.001) and pass rate (38.4% versus 12.5%, respectively; p = 0.0002). In a subgroup analysis of the new module group, students who enrolled in the graduate entry program (an accelerated four-year curriculum consisting of students who have already completed an undergraduate university degree) were more likely to perform better in terms of average score (72.2% versus 57%, respectively; p \u3c 0.001) and pass rates (70.9% versus 21.4%, respectively; p \u3c 0.001) compared with students who had enrolled via the traditional undergraduate route. In terms of satisfaction rates, the new module group reported a significantly higher satisfaction rate than that reported by the historical control group (63% versus 15%, respectively; p \u3c 0.001). CONCLUSIONS: In conclusion, the musculoskeletal module described in this paper represents an educational advance at undergraduate (i.e., medical-school) level as demonstrated by the improvement in scores in a validated examination. As pressure on medical curricula grows to accommodate advancing medical knowledge, it is important to continue to improve, assess, and consolidate the position of musculoskeletal medicine in contemporary medical education

Palliative gastrostomy in the setting of voluminous ascites

Objective: We report the indications, methods, and complications of percutaneous gastrostomy/gastrojejunostomy (G/GJ) in patients with voluminous ascites. Methods: Following institutional review board approval, 69 patients (14 male, 55 female, mean age 58±12 years, range 32–89 years) who underwent percutaneous G/GJ with paracentesis were identified from a prospectively acquired database. Electronic medical record data extracted included diagnosis, method of G/GJ insertion, clinical course, and complications, which were graded by The Society of Interventional Radiology (SIR) criteria. Statistics were performed using Graphpad Instat. Results: Sixty-six G and three GJ catheters were placed in 62 patients with malignant and 7 patients with benign disease; 47 procedures were conducted using fluoroscopy and 22 using computed tomography (CT; 10 patients had failed fluoroscopy). Sixty-six patients had 1980±1371 mL (range, 20–5000 mL) ascites drained (more in males, p=0.01) 0.8±1.6 days (range, 0–5 days) prior to placement. Forty-one patients had significantly less ascites (1895±1426 mL; range, 100–5400 mL) drained after G/GJ (p>0.0.5). Mean survival after insertion was 43±57 days (range, 1–252 days) among 38 patients for whom data were available. Fifty-six patients had a mean postprocedure hospital stay of 8.6±8.4 days (range, 0–45 days); 3 were outpatients and 10 patients died in the hospital. Successful gastropexy was confirmed on subsequent cross-sectional imaging in 22 of 25 patients. There were 25 tube maintenance issues that included catheter displacement and leakage, one patient experienced hemorrhage, and there were two deaths. All except one patient had satisfactory gastrostomy function. Conclusion: Effective G/GJ placement is possible in most patients with voluminous ascites provided ascites is drained and gastrocutaneous fistula formation occurs. Caution is advised; placement is generally for fragile terminal patients, and fluoroscopy or CT guidance is required

Quality of Life Assessment in Spina Bifida for Children (QUALAS-C): Development and Validation of a Novel Health-related Quality of Life Instrument

Objective To develop and validate a self-reported health-related QUAlity of Life Assessment in Spina bifida for Children (QUALAS-C). Methods We drafted a 27-question pilot instrument using a patient-centered comprehensive item generation and refinement process. It was administered to a sample of children 8-12 years old with spina bifida (SB) recruited online via social media and in person at an outpatient SB clinic (January 2013-September 2014). Healthy controls were recruited at routine pediatrician visits. Validation and final questions were determined based on clinical relevance, high loadings on factor analysis, and domain psychometrics. Children with SB also completed the validated generic Kidscreen-27 instrument. Results Median age of 150 participants was 9.6 years (60.7% male, 72.7% Caucasian), similar to 46 controls (P ≥ .10). There were 97 online and 53 clinic participants (89.0% and 84.2% of eligible, respectively). Face and content validities of the 2-domain, 10-question QUALAS-C were established by patients, parents, and experts. Internal consistency and test-retest reliability was high for the Esteem & Independence and Bladder & Bowel domains (Cronbach's alpha: 0.72-0.76, ICC: 0.74-0.77). Correlations between QUALAS-C domains were low (r = 0.51), indicating that QUALAS-C can differentiate between two distinct health-related quality of life components. Correlations between QUALAS-C and Kidscreen-27 were also low (r ≤ 0.44). QUALAS-C scores were significantly lower in children with SB than without (P < .0001). Conclusion QUALAS-C is a short, valid health-related quality of life tool for children with SB. It will be useful in clinical and research settings

Radiographic abnormalities, bladder interventions, and bladder surgery in the first decade of life in children with spina bifida

Background Spina bifida (SB) patients are at increased risk for hydronephrosis, bladder storage and emptying problems, and renal failure that may require multiple bladder surgeries. Methods We retrospectively reviewed patients born with SB 2005–2009, presenting to our institution within 1 year of birth. Outcomes at 8–11 years old included final renal/bladder ultrasound (RBUS) results, clean intermittent catheterization (CIC) use, anticholinergic use, surgical interventions, and final renal function. We excluded those without follow-up past age 8 and/or no RBUS or fluoroscopic urodynamic images (FUI) within the first year of life. Imaging was independently reviewed by four pediatric urologists blinded to radiologists’ interpretation and initial findings compared with final outcomes. Results Of 98 children, 62 met inclusion criteria (48% male, 76% shunted). Median age at last follow-up was 9.6 years. Upon initial imaging, 74% had hydronephrosis (≥ SFU grade 1), decreasing to 5% at 10 years (p < 0.0001). Initially, 9% had ≥ SFU grade 3 hydronephrosis, decreasing to 2% (p = 0.13). CIC and anticholinergic use increased from 61% and 37% to 87% and 86%, respectively (p = 0.001 and p < 0.0001, respectively). With follow-up, 55% had surgical intervention and 23% had an augmentation. Of children with a serum creatinine/cystatin-C at 8–11 years old, one had confirmed chronic kidney disease (stage 2). Conclusions Despite initial high incidence of hydronephrosis, this was low grade and resolved in the first decade of life. Additionally, the 8–11-year incidence of kidney disease and upper tract changes was low due to aggressive medical management

Validation of QUALAS-T, a health-related quality of life instrument for teenagers with spina bifida

Introduction We aimed to develop and validate a self-reported QUAlity of Life Assessment in Spina bifida for Teenagers (QUALAS-T). Material and methods We drafted a 46-question pilot instrument using a patient-centered comprehensive item generation/refinement process. A group of 13–17 years olds with spina bifida (SB) was recruited online via social media and in person at SB clinics (2013–2015). Healthy controls were recruited during routine pediatrician visits. Final questions were identified based on clinical relevance, factor analysis and domain psychometrics. Teenagers with SB completed the validated generic Kidscreen-27 instrument. Results Median age of 159 participants was 15.2 years (42.0% male, 77.4% Caucasian), similar to 58 controls (p ≥ 0.06). There were 102 online and 57 clinic participants (82.8% of eligible). Patients, parents and an expert panel established face and content validity of the 2-domain, 10-question QUALAS-T. Internal consistency and test-retest reliability were high for the Family and Independence and Bladder and Bowel domains (Cronbach's alpha: 0.76–0.78, ICC: 0.72–0.75). The Bladder and Bowel domain is the same for QUALAS-T , QUALAS-A for adults and QUALAS-C for children. Correlations between QUALAS-T domains were low (r = 0.34), indicating QUALAS-T can differentiate between distinct HRQOL components. Correlations between QUALAS-T and Kidscreen-27 were also low (r ≤0.41). QUALAS-T scores were lower in teenagers with SB than without (p <0.0001). Conclusions QUALAS-T is a short, valid HRQOL tool for adolescents with SB, applicable in clinical and research settings. Since the Bladder & Bowel domains for all QUALAS versions are the same, Bladder and Bowel HRQOL can be measured on the same scale from age 8 through adulthood

An imbalance in progenitor cell populations reflects tumour progression in breast cancer primary culture models

Many factors influence breast cancer progression, including the ability of progenitor cells to sustain or increase net tumour cell numbers. Our aim was to define whether alterations in putative progenitor populations could predict clinicopathological factors of prognostic importance for cancer progression.Journal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe

Reduced mRNA abundance of the main enzymes involved in methionine metabolism in human liver cirrhosis and hepatocellular carcinoma

BACKGROUND/AIMS: It has been known for at least 50 years that alterations in methionine metabolism occur in human liver cirrhosis. However, the molecular basis of this alteration is not completely understood. In order to gain more insight into the mechanisms behind this condition, mRNA levels of methionine adenosyltransferase (MAT1A), glycine methyltransferase (GNMT), methionine synthase (MS), betaine homocysteine methyltransferase (BHMT) and cystathionine beta-synthase (CBS) were examined in 26 cirrhotic livers, five hepatocellular carcinoma (HCC) tissues and ten control livers. METHODS: The expression of the above-mentioned genes was determined by quantitative RT-PCR analysis. Methylation of MAT1A promoter was assessed by methylation-sensitive restriction enzyme digestion of genomic DNA. RESULTS: When compared to normal livers MAT1A, GNMT, BHMT, CBS and MS mRNA contents were significantly reduced in liver cirrhosis. Interestingly, MAT1A promoter was hypermethylated in the cirrhotic liver. HCC tissues also showed decreased mRNA levels of these enzymes. CONCLUSIONS: These findings establish that the abundance of the mRNA of the main genes involved in methionine metabolism is markedly reduced in human cirrhosis and HCC. Hypermethylation of MAT1A promoter could participate in its reduced expression in cirrhosis. These observations help to explain the hypermethioninemia, hyperhomocysteinemia and reduced hepatic glutathione content observed in cirrhosis

Climate sensitivity of shrub growth across the tundra biome

The tundra biome is experiencing rapid temperature increases that have been linked to a shift in tundra vegetation composition towards greater shrub dominance. Shrub expansion can amplify warming by altering the surface albedo, energy and water balance, and permafrost temperatures. To account for these feedbacks, global climate models must include realistic projections of vegetation dynamics, and in particular tundra shrub expansion, yet the mechanisms driving shrub expansion remain poorly understood. Dendroecological data consisting of multi-decadal time series of annual growth of shrub species provide a previously untapped resource to explore climate-growth relationships across the tundra biome. We analysed a dataset of approximately 42,000 annual growth records from 1821 individuals, comprising 25 species from eight genera, from 37 arctic and alpine sites. Our analyses demonstrate that the sensitivity of shrub growth to climate was (1) heterogeneous across the tundra biome, (2) greater at sites with higher soil moisture and (3) strongest for taller shrub species growing at the northern or upper elevational edge of their range. Across latitudinal gradients in the Arctic, climate sensitivity of growth was greatest at the boundary between low- and high-arctic vegetation zones, where permafrost conditions are changing and the majority of the global permafrost soil carbon pool is stored. Thus, in order to more accurately estimate feedbacks among shrub change, albedo, permafrost thaw, carbon storage and climate, the observed variation in climate-growth relationships of shrub species across the tundra biome will need to be incorporated into earth system models.JRC.H.3-Forest Resources and Climat

Protein interaction network of alternatively spliced isoforms from brain links genetic risk factors for autism

Increased risk for autism spectrum disorders (ASD) is attributed to hundreds of genetic loci. The convergence of ASD variants have been investigated using various approaches, including protein interactions extracted from the published literature. However, these datasets are frequently incomplete, carry biases and are limited to interactions of a single splicing isoform, which may not be expressed in the disease-relevant tissue. Here we introduce a new interactome mapping approach by experimentally identifying interactions between brain-expressed alternatively spliced variants of ASD risk factors. The Autism Spliceform Interaction Network reveals that almost half of the detected interactions and about 30% of the newly identified interacting partners represent contribution from splicing variants, emphasizing the importance of isoform networks. Isoform interactions greatly contribute to establishing direct physical connections between proteins from the de novo autism CNVs. Our findings demonstrate the critical role of spliceform networks for translating genetic knowledge into a better understanding of human diseases