Explore the vast range of titles available.

The four chambers of the human heart play distinct roles in the maintenance of normal cardiac function, and are differentially affected by inherited/acquired cardiovascular disease. To probe the molecular determinants of these functional differences, we examined mRNA and lncRNA expression profiles in the left (LA) and right (RA) atria, the left (LV) and right (RV) ventricles, and the interventricular septum (IVS) of non-failing human hearts (N = 8). Analysis of paired atrial and ventricular samples (n = 40) identified 5,747 mRNAs and 2,794 lncRNAs that were differentially (>1.5 fold; FDR < 0.05) expressed. The largest differences were observed in comparisons between the atrial (RA/LA) and ventricular (RV/LV/IVS) samples. In every case (e.g., LA vs LV, LA vs RV, etc.), >2,300 mRNAs and >1,200 lncRNAs, corresponding to 17–28% of the total transcripts, were differentially expressed. Heterogeneities in mRNA/lncRNA expression profiles in the LA and RA, as well as in the LV, RV and IVS, were also revealed, although the numbers of differentially expressed transcripts were substantially smaller. Gender differences in mRNA and lncRNA expression profiles were also evident in non-failing human atria and ventricles. Gene ontology classification of differentially expressed gene sets revealed chamber-specific enrichment of numerous signaling pathways.

Markov models of ion channel dynamics have evolved as experimental advances have improved our understanding of channel function. Past studies have examined limited sets of various topologies for Markov models of channel dynamics. We present a systematic method for identification of all possible Markov model topologies using experimental data for two types of native voltage-gated ion channel currents: mouse atrial sodium currents and human left ventricular fast transient outward potassium currents. Successful models identified with this approach have certain characteristics in common, suggesting that aspects of the model topology are determined by the experimental data. Incorporating these channel models into cell and tissue simulations to assess model performance within protocols that were not used for training provided validation and further narrowing of the number of acceptable models. The success of this approach suggests a channel model creation pipeline may be feasible where the structure of the model is not specified a priori .

Mutations affecting the expression of dystrophin result in progressive loss of skeletal muscle function and cardiomyopathy leading to early mortality. Interestingly, clinical studies revealed no correlation in disease severity or age of onset between cardiac and skeletal muscles, suggesting that dystrophin may play overlapping yet different roles in these two striated muscles. Since dystrophin serves as a structural and signaling scaffold, functional differences likely arise from tissue-specific protein interactions. To test this, we optimized a proteomics-based approach to purify, identify and compare the interactome of dystrophin between cardiac and skeletal muscles from as little as 50 mg of starting material. We found selective tissue-specific differences in the protein associations of cardiac and skeletal muscle full length dystrophin to syntrophins and dystrobrevins that couple dystrophin to signaling pathways. Importantly, we identified novel cardiac-specific interactions of dystrophin with proteins known to regulate cardiac contraction and to be involved in cardiac disease. Our approach overcomes a major challenge in the muscular dystrophy field of rapidly and consistently identifying bona fide dystrophin-interacting proteins in tissues. In addition, our findings support the existence of cardiac-specific functions of dystrophin and may guide studies into early triggers of cardiac disease in Duchenne and Becker muscular dystrophies.

Muscle side population (SP) cells are rare multipotent stem cells that can participate in myogenesis and muscle regeneration upon transplantation. While they have been primarily studied for the development of cell-based therapies for Duchenne muscular dystrophy, little is known regarding their non-muscle lineage choices or whether the dystrophic muscle environment affects their ability to repair muscle. Unfortunately, the study of muscle SP cells has been challenged by their low abundance and the absence of specific SP cell markers. To address these issues, we developed culture conditions for the propagation and spontaneous multi-lineage differentiation of muscle SP cells. Using this approach, we show that SP cells from wild type muscle robustly differentiate into satellite cells and form myotubes without requiring co-culture with myogenic cells. Furthermore, this myogenic activity is associated with SP cells negative for immune (CD45) and vascular (CD31) markers but positive for Pax7, Sca1, and the mesenchymal progenitor marker PDGFRα. Additionally, our studies revealed that SP cells isolated from dystrophic or cardiotoxin-injured muscle fail to undergo myogenesis. Instead, these SP cells rapidly expand giving rise to fibroblast and adipocyte progenitors (FAPs) and to their differentiated progeny, fibroblasts and adipocytes. Our findings indicate that muscle damage affects the lineage choices of muscle SP cells, promoting their differentiation along fibro-adipogenic lineages while inhibiting myogenesis. These results have implications for a possible role of muscle SP cells in fibrosis and fat deposition in muscular dystrophy. In addition, our studies provide a useful in vitro system to analyze SP cell biology in both normal and pathological conditions.

The Model for End-Stage Liver Disease Sodium Model (MELD-Na) is a validated scoring system that uses bilirubin, international normalized ratio, serum creatinine, and sodium to predict mortality in cirrhotic patients awaiting liver transplantation. The aim of this study was to identify the utility of MELD-Na to predict patient outcomes, with and without liver disease, after elective colon cancer surgery. A review of the American College of Surgeons National Surgical Quality Improvement Program database (2005 to 2010) was conducted to calculate risk-adjusted 30-day outcomes using regression modeling. A total of 10,842 patients (mean age, 68 years; 51% women) were included. MELD-Na scores were higher in men (10.2 vs 9.1, P < .001) and in open procedures (9.9 vs 9.1, P < .001). The overall complication and mortality rates were 26.3% and 3.3%, respectively. Incremental increases in MELD-Na score correlated with a 1.2% increase in mortality and a 1.1% increase in complications. On multivariate analysis, complications increased with MELD-Na score (odds ratio [OR], 1.05 per 1 point increase; 95% confidence interval [CI], 1.038 to 1.066). MELD-Na score was also associated with increased mortality (OR, 1.13; 95% CI, 1.1 to 1.16), along with ascites (OR, 5.7; 95% CI, 3.7 to 8.8) and corticosteroids (OR, 2.1; 95% CI, 1.3 to 3.3). Elevated preoperative MELD-Na score is significantly associated with worse outcomes after elective resection for colon cancer.

The dystroglycan complex contains the transmembrane protein β-dystroglycan and its interacting extracellular mucin-like protein α-dystroglycan. In skeletal muscle fibers, the dystroglycan complex plays an important structural role by linking the cytoskeletal protein dystrophin to laminin in the extracellular matrix. Mutations that affect any of the proteins involved in this structural axis lead to myofiber degeneration and are associated with muscular dystrophies and congenital myopathies. Because loss of dystrophin in Duchenne muscular dystrophy (DMD) leads to an almost complete loss of dystroglycan complexes at the myofiber membrane, it is generally assumed that the vast majority of dystroglycan complexes within skeletal muscle fibers interact with dystrophin. The residual dystroglycan present in dystrophin-deficient muscle is thought to be preserved by utrophin, a structural homolog of dystrophin that is up-regulated in dystrophic muscles. However, we found that dystroglycan complexes are still present at the myofiber membrane in the absence of both dystrophin and utrophin. Our data show that only a minority of dystroglycan complexes associate with dystrophin in wild type muscle. Furthermore, we provide evidence for at least three separate pools of dystroglycan complexes within myofibers that differ in composition and are differentially affected by loss of dystrophin. Our findings indicate a more complex role of dystroglycan in muscle than currently recognized and may help explain differences in disease pathology and severity among myopathies linked to mutations in DAPC members.

Anastomotic leak after sigmoidectomy for diverticular disease can have devastating consequences. Preservation or sacrifice of the descending colon or rectal arterial supply may affect the anastomosis. The aim of this study was to evaluate whether preservation of the inferior mesenteric artery (IMA) or superior rectal artery (SRA) was associated with a decreased anastomotic leak rate. A retrospective review of adult patients undergoing sigmoidectomies from 2 military tertiary care centers was performed, evaluating patient demographic and operative variables for their effects on anastomotic leak rate. A total of 130 patients were identified. The overall anastomotic leak rate was 5.4%. Laparoscopy was used in 41%, and stapled anastomoses were used in 91%. The IMA was sacrificed in 29% and the SRA in 37%. There were no significant differences in leak rates when the IMA or SRA was sacrificed (0% and 3.7% with the IMA and SRA sacrificed, 9.3% and 6.5% with the vessels preserved; P = .140 and P = .610, respectively). Laparoscopic technique ( P = .843), emergency surgery ( P = .29), and operative time ( P = .78) did not affect leak rate. Hand-sewn anastomoses were associated with a higher leak rate (33% vs 2%; odds ratio, 3.44; 95% confidence interval, 1.514–7.817; P < .001). IMA or SRA preservation or sacrifice was not associated with an increased leak rate from colorectal anastomoses after sigmoidectomy for diverticular disease. Stapled anastomoses were associated with a lower leak rate than hand-sewn anastomoses.

Modern 64- to 128-slice computed tomography (CT) scanners have questioned the need for routine colonoscopy after hospital admission for presumed uncomplicated diverticulitis. This is a retrospective review of all patients (>18 years) who underwent planned colonoscopy after admission for Hinchey I or II acute diverticulitis (January 2009 to January 2014). The findings on the final radiologist report were then correlated with the colonoscopy results. In total, 110 patients (mean age, 55.2 ± 16; 46.4% female) underwent a subsequent colonoscopy (median, 60 days) after admission for diverticulitis. Overall, 102 patients (92.7%) had CT findings consistent with definitive diverticulitis, 6 patients had a diagnosis suggestive of diverticulitis on CT scan, and 2 patients had masses on their admission CT scans. Within the group with definitive diverticulitis, follow-up colonoscopy identified diverticulosis in 99 (97.0%), whereas the other 3 had normal findings. Of the patients with CT scans suggestive of diverticulitis, follow-up colonoscopy showed 3 with diverticulosis, 2 with malignancies, and 1 with nonspecific inflammation. The reliability of CT scans for diverticulitis compared with colonoscopy was found to have a kappa = .829 (P < .001; 95% confidence interval, .629, 1.21). Follow-up colonoscopy should be performed when a CT scan suggests malignancy, nonspecific inflammatory findings, or the patient is otherwise due for routine screening or surveillance. In this study, there was no benefit of follow-up colonoscopy in patients with CT-confirmed diverticulitis in the absence of other concerning or indeterminate findings. •Colonoscopy after an uncomplicated episode of diverticulitis has been questioned.•Follow-up colonoscopy identified diverticulosis in the vast majority of patients.•No benefit of follow-up colonoscopy in patients with uncomplicated diverticulitis.

Pilonidal disease (PD) has a long connection with military personnel, even nicknamed “jeep disease” during World War II. The aim of this study was to identify factors associated with recurrence and complications after surgery in a military population. A retrospective cohort analysis of operative therapy for PD at a single institution from 2005 to 2011 was conducted. Patient demographics, disease characteristics, and surgical methods were assessed for the primary outcomes of recurrence and morbidity. A total of 151 patients with PD were identified, who underwent excision (45.7%), excision with primary closure (29.8%), and incision and drainage (9.9%). Overall recurrence and morbidity rates were 27.2% and 34.4%, respectively. Black race, chronic disease, wound infection, and infection and drainage were associated with recurrence (P < .05), and excision with primary closure was associated with increased complications (P < .001). PD remains a significant source of morbidity and recurrence among military personnel. Certain patient-related and disease-related factors portend a worse prognosis, with black race and operative method the strongest predictors of outcomes.

Background Detection of colorectal cancer ideally occurs at an early stage through proper screening. We sought to establish methods by which colorectal cancers are diagnosed within an equal access military health care population and evaluate the correlation between TNM stage at colorectal cancer diagnosis and diagnostic modality (i.e., symptomatic detection vs screen detection). Materials and Methods A retrospective chart review of all newly diagnosed colorectal cancer patients from January 2007 to August 2014 was conducted at the authors’ equal access military institution. We evaluated TNM stage relative to diagnosis by screen detection (fecal occult blood test, flexible sigmoidoscopy, CT colonography, colonoscopy) or symptomatic evaluation (diagnostic colonoscopy or surgery). Results Of 197 colorectal cancers diagnosed (59 % male; mean age 62 years), 50 (25 %) had stage I, 47 (24 %) had stage II, 70 (36 %) had stage III, and 30 (15 %) had stage IV disease. Twenty-five percent of colorectal cancers were detected via screen detection (3 % by fecal occult blood testing (FOBT), 0.5 % by screening CT colonography, 17 % by screening colonoscopy, and 5 % by surveillance colonoscopy). One hundred forty-eight (75 %) were diagnosed after onset of signs or symptoms. The preponderance of these was advanced-stage disease (stages III–IV), although >50 % of stage I–II disease also had signs or symptoms at diagnosis. The most common symptoms were rectal bleeding (45 %), abdominal pain (35 %), and change in stool caliber (27 %). The most common overall sign was anemia (60 %). Screening FOBT (odds ratio (OR) 8.7, 95 % confidence interval (CI) 1.0–78.3; P  = 0.05) independently predicted early diagnosis with stage I–II disease. Patient gender and ethnicity were not associated with cancer stage at diagnosis. Conclusions Despite equal access to colorectal cancer screening, diagnosis after development of symptomatic cancer remains more common. Fecal occult blood screen detection is associated with early stage at colorectal cancer diagnosis and is the focus for future initiatives.