Comparative analysis of the mitochondrial proteins reveals complex structural and functional relationships in Fasciola species.

Mitochondria is a cellular source of energy, appears to play an essential role in dealing with cellular stress induced by environmental stimuli. The genetic diversity of mitochondrial genes involved in oxidative phosphorylation affecting the production of cellular energy and regional adaptation to various ecological (climatic) pressures affecting amino acid sequences (variants of protein). However, little is known about the combined effect of protein changes on cell-level metabolic alterations in simultaneous exposure to various environmental conditions, including mitochondrial dysfunction and oxidative stress induction. The present study was designed to address this issue by analyzing the mitochondrial proteins in Fasciola species including Cytochrome oxidase (COX1, COX2, COX3, and CYTB) and NADH dehydrogenase (ND1, ND2, ND3, ND4, ND5, and ND6). Mitochondrial proteins were used for detailed computational investigation, using available standard bioinformatics tools to exploit structural and functional relationships. These proteins in Fasciola hepatica, Fasciola gigentica, and Fasciola jacksoni were functionally annotated using public databases. The results showed that the protein of COX1 of F. hepatica, F. gigantica, and F. jacksoni consist of 510, 513, and 517 amino acids, respectively. The alignment of proteins showed that these proteins are conserved in the same regions at ten positions in COX and CYTB proteins while at twelve locations in NADH. Three-dimensional structure of COX, CYTB, and NADH proteins were compared and showed differences in additional conserved and binding sites in COX and CYTB proteins as compared to NADH in three species of Fasciola. These results based on the amino acid diversity pattern were used to identify sites in the enzyme and the variations in mitochondrial proteins among Fasciola species. Our study provides valuable information for future experimental studies, including identification of therapeutic, diagnostic, and immunoprophylactic interests with novel mitochondrial proteins.

Study on colorectal cancer presentation, treatment and follow-up.

BACKGROUND: Colorectal carcinoma (CRC) is the second most common cancer in women and men affecting 9.7 % population worldwide. Although CRC mortality has been progressively declining since 1990 at a rate of about 3 % per year, it still remains the third most common cause of cancer deaths. OBJECTIVE: The objective of this study is to evaluate the patterns of clinical presentation, treatment options and follow-up of colorectal carcinoma. METHODOLOGY: Medical records of patients with colorectal carcinoma admitted at St. Luke's Hospital Kilkenny from January 2009 to December 2014 were included in the study. RESULTS: Out of 113, 57 were males and 28 were 75 years or older. Sixty-seven percent presented in the outpatient clinic. The main presentation symptom was bleeding per rectum (40 %), followed by abdominal pain, altered bowel habit, bowel obstruction and weight loss. Mean time delay was 4.79, 6.20 and 4.83 weeks for surgical outpatient department (SOPD), colonoscopy and surgery, respectively. Ninety-eight percent of patients underwent preoperative staging with computed tomography of thorax, abdomen and pelvis (CTTAP) and 78 % had preoperative carcinoembryonic antigen (CEA) measurement. Thirty-four percent of cancers had already metastasized to distant organs. Twenty five percent underwent a right hemicolectomy. Seventy-eight percent received a primary anastomosis. Ninety-five percent achieved a R0 resection. Sixty-two percent were given adjuvant chemotherapy. Seventy-six percent had surgery follow-up and 57 % had excellent follow-up. Cancer recurred in two patients. Thirty day mortality was 2 %. CONCLUSION: Our study shows that the mean age group at risk for colorectal cancer is 65 years (range 54-75). Still, 33 % of patients present to acute surgical assessment units with advanced disease. Though we did well in terms of operative resections, follow-up still remains a challenge.

Deficient cytokine control modulates temporomandibular joint pain in rheumatoid arthritis.

The aim was to investigate how endogenous cytokine control of tumor necrosis factor (TNF) influences temporomandibular joint (TMJ) pain in relation to the role of anti-citrullinated peptide antibodies (ACPA) in patients with rheumatoid arthritis (RA). Twenty-six consecutive patients with TMJ RA were included. Temporomandibular joint pain intensity was assessed at rest, on maximum mouth opening, on chewing, and on palpation. Mandibular movement capacity and degree of anterior open bite (a clinical sign of structural destruction of TMJ tissues) were also assessed. Systemic inflammatory activity was assessed using the Disease Activity Score in 28 joints (DAS28) for rheumatoid arthritis. Samples of TMJ synovial fluid and blood were obtained and analyzed for TNF, its soluble receptor, soluble TNF receptor II (TNFsRII), and ACPA. A high concentration of TNF in relation to the concentration of TNFsRII in TMJ synovial fluid was associated with TMJ pain on posterior palpation on maximum mouth opening. The ACPA concentration correlated significantly to the TNF concentration, but not to the TNFsRII concentration, indicating that increased inflammatory activity is mainly caused by an insufficient increase in anti-inflammatory mediators. This study indicates that TMJ pain on palpation in patients with RA is related to a deficiency in local cytokine control that contributes to increased inflammatory activity, including sensitization to mechanical stimuli over the TMJ.

Tumor necrosis factor mediates temporomandibular joint bone tissue resorption in rheumatoid arthritis.

OBJECTIVE: To investigate if TNF, IL-1 or their endogenous controls, in relation to ACPA, are associated with radiological signs of ongoing temporomandibular joint (TMJ) bone tissue resorption and disc displacement in RA patients. METHODS: Twenty-two consecutive outpatients with TMJ of RA were included. Systemic inflammatory activity was assessed by DAS28. The number of painful regions in the body and ESR, CRP, RF and ACPA were analyzed. TMJ synovial fluid and blood samples were obtained and analyzed for TNF, TNFsRII, IL-1ra, IL-1sRII and ACPA. The ratios between the mediators and their endogenous control receptors were used in the statistical analysis. Magnetic resonance imaging was performed in closed- and open-mouth positions and evaluated regarding disc position and presence of condylar and temporal erosions of the TMJ. RESULTS: A high TNF level in relation to TNFsRII in TMJ synovial fluid correlated to the degree of TMJ condylar erosion. A high IL-1ra level in relation to TNF in TMJ synovial fluid was also correlated to the degree of TMJ condylar erosion. The total degree of TMJ condylar erosion was correlated with the number of painful regions. CONCLUSION: This study indicates that TNF in TMJ synovial fluid mediates TMJ cartilage and bone tissue resorption in RA. The study also suggests that the degree of endogenous cytokine control is of importance for development of bone tissue destruction.

New control model for autonomous vehicles using integration of Model Predictive and Stanley based controllers.

In this paper, a robust control method is introduced for autonomous vehicle control in different scenarios. Dual controllers have been used in this method to ensure high performance and low errors during the vehicle's trip. The new control system is called Model Predictive and Stanley based controller (MPS), which is an integration of a model predictive controller and a Stanley controller. Each of these two controllers has its drawbacks and weaknesses. The proposed method tries to overcome these points and come up with a high-performance control system. This hybrid way of combining two of the famous controllers has the benefit of using the best part of each one and trying to enhance the other part. The MPS is tested for both path-following and vehicle control in different scenarios and on both straight and curved roads. This controller has shown high performance and flexibility to deal with different scenarios of autonomous driving. The results are compared to previous types of controllers, and the proposed system outperformed these types.

Impact of temporomandibular joint pain in rheumatoid arthritis.

To investigate the impact of temporomandibular joint (TMJ) pain on daily activities and quality of life in relation to systemic inflammatory activity in patients with rheumatoid arthritis (RA), thirty-three consecutive outpatients with RA were included. TMJ pain intensity at rest, on maximum mouth opening, and on chewing was assessed on a 0-10 numerical rating scale. TMJ palpatory tenderness, degree of anterior open bite, the impact of TMJ pain on daily activities and quality of life were also assessed. The systemic inflammatory activity was estimated by the disease activity score 28 (DAS28), blood levels of inflammatory markers and number of painful musculoskeletal regions. TMJ pain at rest, on maximum mouth opening, and on chewing as well as DAS28 was correlated with the impact of the TMJ pain on daily activities and quality of life. Partial correlations showed a significant interaction between TMJ pain on movement and DAS28 that explained the TMJ pain impact on daily activities and quality of life to a significant degree. This study indicates that both current TMJ pain intensity and systemic inflammatory activity play roles in the impact of TMJ pain on daily living and quality of life in RA.

A rare case of duodenal angiodysplasia-a case report.

Gastrointestinal bleeding can be manifested as a variety of symptoms and, often, it is difficult to classify as upper or lower gastrointestinal bleeding on mere symptomatology. This is a case report of a similar kind of patient who initially was diagnosed with fresh per rectum bleeding, subsequently diagnosed as bleeding angiodysplasia in duodenal diverticulum by a series of investigations and management including urgent oesophageal-gastroduodenoscopy (OGD), laparotomy, followed by computerized tomography-angiogram. As diagnosis was established after laparotomy, the patient was kept intubated and IR selective embolization was performed. Keeping this case report in view, it can be suggested that bleeding vascular malformation in any part duodenum should be considered as a cause of massive upper GI bleeding. Furthermore, if operative intervention is indicated, it should be preceded by OGD, not only for a therapeutic purpose but also as an adjunct for guidance for the operative plan.

Genetic Association of Beta-Myosin Heavy-Chain Gene (MYH7) with Cardiac Dysfunction.

Cardiac dysfunction accelerates the risk of heart failure, and its pathogenesis involves a complex interaction between genetic and environmental factors. Variations in myosin affect contractile abilities of cardiomyocytes and cause structural and functional abnormalities in myocardium. The study aims to find the association of MYH7 rs121913642 (c.1594 T>C) and rs121913645 (c.667G>A) variants with cardiac dysfunction in the Punjabi Pakistani population. Patients with heart failure (n = 232) and healthy controls (n = 205) were enrolled in this study. MYH7 variant genotyping was performed using tetra ARMS-PCR. MYH7 rs121913642 TC genotype was significantly more prevalent in the patient group (p < 0.001). However, MYH7 rs121913645 genotype frequencies were not significantly different between the patient and control groups (p < 0.666). Regression analysis also revealed that the rs121913642 C allele increases the risk of cardiac failure by ~2 [OR:1.98, CI: 1.31−2.98, p < 0.001] in comparison to the T allele. High levels of the cardiac enzymes cardiac troponin I (cTnI) and CK-MB were observed in patients. There was also an increase in total cholesterol, LDL cholesterol, and uric acid in patients compared to the healthy control group (p < 0.001). In conclusion, the MYH7 gene variant rs121913642 is genetically associated with cardiac dysfunction and involved in the pathogenesis of HF.

Metastasis from scapular Ewing's sarcoma presenting as sutural diastasis: An unusual presentation.

Ewing's sarcoma is a malignant non-osteogenic primary tumor of the bone. It is one of the most common primary malignant tumors of bone. Peak incidence is noticed in second decade of life with male preponderance of 1.6:1. It occurs most frequently in long bones and flat bones of pelvic girdles. In 30% cases, Ewing's sarcoma is multicentric in origin. In 14-50%, multiple metastases are present at the time of diagnosis. CNS spread is rare and isolated CNS involvement is not seen. Skull metastasis of Ewing's sarcoma is not rare compared to primary Ewing's sarcoma of the skull, but the actual frequency is unknown. We wish to report a case of "Primary Ewing's sarcoma of scapula with metastasis to Skull Vault in a Child resulting in sutural diastasis" diagnosed by clinicoradiological examination and confirmed by histopathology.