Synthesis of temporomandibular disorders management intervention outcomes for development of core outcome sets: A systematic review.

INTRODUCTION: The selection of appropriate outcomes in clinical trials and systematic reviews is a crucial factor in determining the results that are useful, reliable, and relevant for both patients and healthcare professionals. Clinicians and researchers have been encouraged to develop and apply core outcome sets (COS) to minimise the discrepancy between studies. AIM: This systematic review is the first phase of the COS development project for clinical trials in temporomandibular disorders (COS-TMD). It aims to identify and synthesise the outcomes used in the randomised controlled trials (RCT) that evaluated the effectiveness of interventions used in TMD management. MATERIALS AND METHODS: An electronic search was performed in several databases: MEDLINE (via PubMed), Scopus, Web of Science, Cochrane Library and EMBASE. The eligibility criteria comprised RCT that applied any intervention to treat temporomandibular joint disorders or masticatory muscle disorders. The identified outcomes were categorised according to domains of the Initiative on Methods, Measurement and Pain Assessment in Clinical Trials (IMMPACT). RESULTS: The electronic search resulted in 1606 studies. After removing duplicates and applying the eligibility criteria, 106 RCT were included. A total of 43 studies evaluated masticatory muscle disorders, 27 evaluated temporomandibular joint disorders, and 36 analysed mixed TMD. CONCLUSIONS: The evaluation showed significant variability in the types of outcomes and their measurement instruments. In addition, some domains such as physical and emotional functioning, participant ratings of global improvement and adverse events have been neglected when determining the effectiveness of treatments for TMD.

Screening of Galician grapevine varieties by SNPs, phenotypic traits, and phytopathology.

The genetic erosion of the European grapevine diversity in the last century has promoted the conservation of varieties in germplasm banks to prevent their disappearance. The study of these varieties is necessary as it would allow the diversification of the wine market, as well as provide a source of genes to face new pathogens or climate constraints. In this work, the grapevine varieties preserved in the "Estación de Viticultura e Enoloxía de Galicia" (EVEGA) Germplasm Bank (Ourense, Spain) were widely characterized, combining ampelography, ampelometry, agronomy, and phytopathology. Moreover, genetic characterization was carried out through the analysis of 48 single-nucleotide polymorphisms (SNPs). A Bayesian analysis based on the SNP data was carried out to define the genetic structure of the EVEGA Germplasm Bank, which allowed the differentiation of two main reconstructed panmictic populations (RPPs), confirming previous results obtained based on microsatellite markers (SSRs). A great diversity between varieties was found for almost every parameter evaluated for ampelography, ampelometry, phytopatology, phenology, and berry quality. A principal component analysis (PCA) performed with these phenotypical data allowed discrimination among some groups of varieties included in different genetic populations. This study allowed us to evaluate the grapevine diversity maintained in the EVEGA Germplasm Bank and characterize varieties of potential value for breeding programs of interest for the Galician viticulture.

The Role of Physical Frailty Independent Components on Increased Disabilities in Institutionalized Older Women.

The purpose of this study was to identify the independent components of physical frailty that most influence disability indicators in institutionalized older women. A cross-sectional study with 319 participants (81.96±7.89 years old) was performed. Disability was assessed through dynamic and static balance tests, activities of daily life and falls risk screen. Fried physical frailty protocol was used to access physical frailty. The frail subgroup displayed the weakest results for all disability indicators (p < 0.05). Regression analysis showed that in the two models tested, low physical activity levels and slowness were the physical frailty independent components that better associated with the disability indicators. More studies with larger samples will help to better understand the independent relationship of each physical frailty component with disability outcomes and assist to design a co-adjuvant treatment to reverse physical frailty.

Estudo da técnica de venografia dos dígitos de vacas / Study of Venography technique in digits of cows

O objetivo deste estudo foi descrever a técnica de venografia retrógrada podal em vacas, comparando os acessos da veia digital dorsal comum III com a digital comum II ou IV, nos membros torácicos e pélvicos, mediante a administração de dois diferentes volumes de contraste. Foram utilizados 53 membros torácicos e pélvicos de 14 vacas, com o torniquete de borracha posicionado a 5cm proximal aosparadígitos. Administraram-se 10mL do diatrizoato de meglumina em 24 membros (grupo 1), sendo 13 na veia digital dorsal comum III pelo acesso 1 (A1) e 11 na digital II ou IV no acesso 2 (A2). No grupo 2, administraram-se 20mL em 29 membros, sendo 15 pelo A1 e 19 pelo A2. Após a administração do contraste, as radiografias foram repetidas a cada 20 segundos até 120 segundos. O grau de preenchimento vascular foi maior no grupo 2, não diferindo entre membros e acessos venosos. Conclui-se que a administração de 20mL de contraste apresentou melhor preenchimento vascular e radiopacidade, não havendo diferença entre 20 e 120 segundos após a administração do contraste na qualidade radiográfica, independentemente do acesso venoso.(AU)

The aim of this study was to describe the technique of retrograde venography foot in cows, comparing the approaches of the dorsal common digital vein III with the digital commons II or IV, thoracic and pelvic by administering two different volumes of contrast members. Fifty three fore and hindlimbs of 14 cows were used, a rubber tourniquet was placed at 5cm above accessory digit. Diatrizoatemeglumine was administered at 10mL to 24 members (group 1), 13 dorsal common digital vein III for access 1 (A1), and 11 digital II or IV access 2 (A2). In group 2 20mL was administered to 29 members, 15 by 19 in A1 and A2. After contrast administration, the radiographs were repeated every 20 seconds until 120 seconds. The degree of vascular filling was greater in group 2, independent of venous access, member or moment. There was no significant difference in the degree of radiopacity of radiographic images when compared to the venous access, time and a member of both groups. We conclude that administration of 20mL of contrast showed better vascular filling and radiopacity, with no difference between 20 and 120 seconds after contrast administration in independent radiographic quality venous access.(AU)

Phylogenomics of pike cichlids (Cichlidae: Crenicichla): the rapid ecological speciation of an incipient species flock.

The rapid rise of phenotypic and ecological diversity in independent lake-dwelling groups of cichlids is emblematic of the East African Great Lakes. In this study, we show that similar ecologically based diversification has occurred in pike cichlids (Crenicichla) throughout the Uruguay River drainage of South America. We collected genomic data from nearly 500 ultraconserved element (UCEs) loci and >260 000 base pairs across 33 species, to obtain a phylogenetic hypothesis for the major species groups and to evaluate the relationships and genetic structure among five closely related, endemic, co-occurring species (the Uruguay River species flock; URSF). Additionally, we evaluated ecological divergence of the URSF based on body and lower pharyngeal jaw (LPJ) shape and gut contents. Across the genus, we recovered novel relationships among the species groups. We found strong support for the monophyly of the URSF; however, relationships among these species remain problematic, likely because of the rapid and recent evolution of this clade. Clustered co-ancestry analysis recovered most species as well delimited genetic groups. The URSF species exhibit species-specific body and LPJ shapes associated with specialized trophic roles. Collectively, our results suggest that the URSF consists of incipient species that arose via ecological speciation associated with the exploration of novel trophic roles.

Src family kinases Fyn and Lyn are constitutively activated and mediate plasmacytoid dendritic cell responses.

Plasmacytoid dendritic cells (pDC) are type I interferon-producing cells with critical functions in a number of human illnesses; however, their molecular regulation is incompletely understood. Here we show the role of Src family kinases (SFK) in mouse and human pDCs. pDCs express Fyn and Lyn and their activating residues are phosphorylated both before and after Toll-like receptor (TLR) stimulation. Fyn or Lyn genetic ablation as well as treatment with SFK inhibitors ablate pDC (but not conventional DC) responses both in vitro and in vivo. Inhibition of SFK activity not only alters TLR-ligand localization and inhibits downstream signalling events, but, independent of ex-vivo TLR stimulation, also affects constitutive phosphorylation of BCAP, an adaptor protein bridging PI3K and TLR pathways. Our data identify Fyn and Lyn as important factors that promote pDC responses, describe the mechanisms involved and highlight a tonic SFK-mediated signalling that precedes pathogen encounter, raising the possibility that small molecules targeting SFKs could modulate pDC responses in human diseases.

Long-term exercise training prevents mammary tumorigenesis-induced muscle wasting in rats through the regulation of TWEAK signalling.

AIM: Exercise training has been suggested as a non-pharmacological approach to prevent skeletal muscle wasting and improve muscle function in cancer cachexia. However, little is known about the molecular mechanisms underlying such beneficial effect. In this study, we aimed to, firstly, examine the contribution of TWEAK signalling to cancer-induced skeletal muscle wasting and, secondly, evaluate whether long-term exercise alters TWEAK signalling and prevents muscle wasting. METHODS: Female Sprague-Dawley rats were randomly assigned to control and exercise groups. Fifteen animals from each group were exposed to N-Methyl-N-nitrosourea carcinogen. Animals in exercise groups were submitted to moderate treadmill exercise for 35 weeks. After the experimental period, animals were killed and gastrocnemius muscles were harvested for morphological and biochemical analysis. RESULTS: We verified that exercise training prevented tumour-induced TWEAK/NF-κB signalling in skeletal muscle with a beneficial impact in fibre cross-sectional area and metabolism. Indeed, 35 weeks of exercise training promoted the upregulation of PGC-1α and oxidative phosphorylation complexes. This exercise-induced muscle remodelling in tumour-bearing animals was associated with less malignant mammary lesions. CONCLUSION: Data support the benefits of an active lifestyle for the prevention of muscle wasting secondary to breast cancer, highlighting TWEAK/NF- κB signalling as a potential therapeutic target for the preservation of muscle mass.

Osmoconditioning prevents the onset of microtubular cytoskeleton and activation of cell cycle and is detrimental for germination of Jatropha curcas L. seeds.

Jatropha curcas is an oilseed crop renowned for its tolerance to a diverse range of environmental stresses. In Brazil, this species is grown in semiarid regions where crop establishment requires a better understanding of the mechanisms underlying appropriate seed, seedling and plant behaviour under water restriction conditions. In this context, the objective of this study was to investigate the physiological and cytological profiles of J. curcas seeds in response to imbibition in water (control) and in polyethylene glycol solution (osmoticum). Seed germinability and reactivation of cell cycle events were assessed by means of different germination parameters and immunohistochemical detection of tubulin and microtubules, i.e. tubulin accumulation and microtubular cytoskeleton configurations in water imbibed seeds (control) and in seeds imbibed in the osmoticum. Immunohistochemical analysis revealed increasing accumulation of tubulin and appearance of microtubular cytoskeleton in seed embryo radicles imbibed in water from 48 h onwards. Mitotic microtubules were only visible in seeds imbibed in water, after radicle protrusion, as an indication of cell cycle reactivation and cell proliferation, with subsequent root development. Imbibition in osmoticum prevented accumulation of microtubules, i.e. activation of cell cycle, therefore germination could not be resumed. Osmoconditioned seeds were able to survive re-drying and could resume germination after re-imbibition in water, however, with lower germination performance, possibly due to acquisition of secondary dormancy. This study provides important insights into understanding of the physiological aspects of J. curcas seed germination in response to water restriction conditions.

Risk of Dumping Syndrome after Sleeve Gastrectomy and Roux-en-Y Gastric Bypass: Early Results of a Multicentre Prospective Study.

Background. Bariatric surgery is an important field of surgery. An important complication of bariatric surgery is dumping syndrome (DS). Aims. To evaluate the incidence of DS in patients undergoing bariatric surgery. Methods. 541 patients included from 5 nutrition and bariatric centers in France underwent either LSG or LRYGB. They were evaluated at 1 month (M1) and 6 months (M6) postoperatively by an interview and completion of a dumping syndrome questionnaire. Results. 268 patients underwent LSG (Group A) and 273 underwent LRYGB. From the LRYGB patients 229 had mechanical gastrojejunoanal anastomosis with 30 mm linear stapler (Group B) and 44 had manual (hand sewn) 15 mm gastrojejunal anastomosis (Group C). Overall incidence of DS was 8.5% at M1 and M6. In LSG group (Group A), only 4 patients (1.49%) reported episodes of DS at M1 and 3 (1.12%) at M6. In Group B, 41 patients (17.90%) reported episodes of DS at M1 and 43 (18.78%) at M6. Group C experienced one case (2.27%) of DS at M1 and none (0%) at M6. Conclusions. Patients undergoing LRYGB, especially with larger gastrojejunal anastomosis, are more prone to developing DS following surgery than patients undergoing LSG or LRYGB with calibrated manual anastomosis.

The association between the HLA-G 14-bp insertion/deletion polymorphism and type 1 diabetes.

Type 1 diabetes (T1D) is a multifactorial disease that has a strong genetic component. The HLA-G is a nonclassical HLA class I locus that is associated with immunomodulatory functions, including downregulation of innate and adaptive immune responses and induction of immune tolerance. However, there is currently limited information about the involvement of HLA-G in T1D susceptibility. This case-control study aims to investigate the T1D susceptibility association of alleles and genotypes of a widely investigated 14-bp insertion/deletion polymorphism in the HLA-G and to provide further evidence of the frequency distribution of class II HLA-DR-DQ-risk genotypes in T1D children and adolescents in the Brazilian population. The deletion allele and the homozygous deletion genotype are associated with susceptibility to T1D and the insertion allele and the heterozygous deletion/insertion genotype are associated with protection from T1D. We also confirm that genetic susceptibility to T1D is associated with the DRB1*03:01-DQA1*05:01-DQB1*02:01 and DRB1*04-DQA1*03:01-DQB1*03:02 haplotypes in Brazilian northeast region. The DR3-DQ2/DR4-DQ8 genotype conferred the highest detected risk for T1D. Our results identify a novel association of the 14-bp deletion allele and the homozygous deletion genotype with T1D development and provide additional evidence of the importance of HLA class II heterozygous DR3-DQ2/DR4-DQ8 genotype in T1D susceptibility.

Clinical and Economic Evaluation of Absorbable Staple Line Buttressing in Sleeve Gastrectomy in High-Risk Patients.

BACKGROUND: Gastric leaks and bleeding are the most important complications after laparoscopic sleeve gastrectomy (LSG). The use of absorbable membranes as staple line reinforcement may decrease this risk. On the other hand, these materials bring additional costs and their economic impact is not well known. The purpose of this study was to assess the clinical and economic performance of one of the commercially available buttressing absorbable materials when treating a high-risk population. METHODS: A retrospective, observational, and comparative study was conducted at Montpellier University Hospital, France, between July 2013 and September 2014. Patients undergoing LSG, who were at a high risk for leaks and bleeding, were included and treated according to two groups: no buttressing (July 2013 to January 2014) and buttressing (February 2014 to September 2014). Clinical and economic outcomes were measured throughout the first 6 months. RESULTS: Two hundred two patients were included in the study: 116 during the no stapling reinforcement period and 86 during the buttressing period. Baseline characteristics were similar. There was no significant difference between the two groups regarding gastric leaks. However, buttressing reduced hemorrhagic complications (0 vs 8.6 %, p = 0.005) and decreased average total hospital costs for the first hospitalization (5768 vs 6025 €, p < 0.001), as well as 6-month total inpatient cost (5944 vs. 6246 €, p < 0.001). CONCLUSIONS: Staple line reinforcement with absorbable material reduces bleeding in high-risk population. Therefore, this type of material can also result in cost-savings.

Prospective, randomized and controlled study of mesh displacement after laparoscopic inguinal repair: fixation versus no fixation of mesh.

INTRODUCTION: Repair of inguinal hernia is one of the most common elective operations performed in general surgery practice. Mesh hernia repair became the gold standard because of its low recurrence rate in comparison with non-tension-free repair. Laparoscopic approach seems to have potential advantages over open techniques, including faster recovery and reduced acute and chronic pain rate. Laparoscopic mesh fixation is usually performed using staples, which is associated with higher cost and risk for chronic pain. Recently, the role of mesh fixation has been questioned by several surgeons. AIM: To evaluate mesh displacement in patients undergoing laparoscopic inguinal hernia repair comparing mesh fixation with no fixation. METHODS: From January 2012 to May 2014, 60 consecutive patients with unilateral inguinal hernia were randomized into two groups: control group--10 patients underwent totally extraperitoneal (TEP) repair with mesh fixation; NO FIX group-50 patients underwent TEP repair with no mesh fixation. Mesh was marked with three 3-mm surgical clips at its medial inferior, medial superior and lateral inferior corners. Mesh displacement was measured by comparing an initial X-ray, performed in the immediate postoperative period, with a second X-ray obtained 30 days later. RESULTS: The mean displacement of all three clips in control group was 0.1-0.35 cm (range 0-1.2 cm), while in NO FIX group was 0.1-0.3 cm (range 0-1.3 cm). The overall displacement of control and NO FIX group did not show any difference (p = 0.50). CONCLUSION: Fixation of the mesh for TEP repair is unnecessary. TEP repair with no mesh fixation is safe and is not associated with increased risk of mesh displacement.

Arsenic-induced responses in Pityrogramma calomelanos (L.) Link: Arsenic speciation, mineral nutrition and antioxidant defenses.

Arsenic (As) hyperaccumulation trait has been described in a limited number of fern species. The physiological basis of hyperaccumulation remains unclear, especially in non-Pteris species such as Pityrogramma calomelanos. Aiming at a better understanding of As-induced responses, P. calomelanos plants were exposed to 1 mM As for 21 days and compared with control plants. Chemical analyses revealed that As accumulation was ten times higher in pinnae then in roots and stipes. In pinnae, As was present mainly as arsenite, whereas arsenate was the dominant form in stipes and roots. Arsenic promoted an increase in antioxidant enzyme activities in both fern parts and several alterations in mineral nutrition, especially with regard to P and K. A higher content of non-protein thiols was observed in pinnae of plants exposed to As, whereas As induced the increase in lipid peroxidation in roots. The results showed that Pityrogramma calomelanos shares with Pteris vittata several aspects of As metabolism. High root-shoot As translocation showed to be essential to avoid toxic effects in roots, since the root is more sensitive to the metalloid. The higher capacity of P. calomelanos to sequester arsenite in the pinna and its efficient antioxidant system maintain the reactive oxygen species at a low level, thus enhancing the continuous accumulation of As. Molecular investigations are needed to elucidate the evolution of As-tolerance mechanisms in Pteridaceae species, especially with regard to membrane transporters and ROS signaling.

Genetic polymorphisms of phase I and phase II metabolic enzymes as modulators of lung cancer susceptibility.

OBJECTIVES: Tobacco exposure remains the main etiologic factor for lung cancer (LC). Interactions between environment and individual genetic profile are particularly important for this disease. The aim of this study was to evaluate the contribution of CYP1A1*2A, CYP1A1*2C, CYP2D6*4, GSTP1, GSTM1, GSTT1 and NAT2 polymorphisms for the susceptibility to LC in a Portuguese population considering their demographic and clinical characteristics. MATERIALS AND METHODS: A total of 200 LC and 247 controls subjects from the Centre of Portugal were studied. Clinical and demographic characteristics were collected from clinical files and by individual questionnaires. Polymorphisms of CYP1A1*2A, CYP1A1*2C, CYP2D6*4, GSTP1, GSTM1, GSTT1 and NAT2 were genotyped using PCR-RFLP, PCR multiplex, ARMS and real time. RESULTS: Gender, family history of cancer, smoke cessation and alcohol consumption were independent risk factors (p < 0.05). Associations found between phases I and II genes and LC population reveal a sex dependent distribution. Logistic regression analysis demonstrates that enhanced activation by CYPs, associated by reduced or loss of function of phase II enzymes, can lead to a greater risk. GSTP1 and NAT2 polymorphisms studied have a significant contribution for the histological tumour types and the presence of metastases, at time of diagnosis, respectively, when males with smoking habits were considered. CONCLUSION: Multiple interactions between environment and individual characteristics are clearly associated to this disease. Variants of the detoxification genes may act synergistically contributing to this disease and modifying the risk posed by smoking and sex. The GSTT1*0 and GSTP1 (Ile462Val) might contribute to the malignant phenotype through different mechanisms.

Defective sarcoplasmic reticulum-mitochondria calcium exchange in aged mouse myocardium.

Mitochondrial alterations are critically involved in increased vulnerability to disease during aging. We investigated the contribution of mitochondria-sarcoplasmic reticulum (SR) communication in cardiomyocyte functional alterations during aging. Heart function (echocardiography) and ATP/phosphocreatine (NMR spectroscopy) were preserved in hearts from old mice (>20 months) with respect to young mice (5-6 months). Mitochondrial membrane potential and resting O2 consumption were similar in mitochondria from young and old hearts. However, maximal ADP-stimulated O2 consumption was specifically reduced in interfibrillar mitochondria from aged hearts. Second generation proteomics disclosed an increased mitochondrial protein oxidation in advanced age. Because energy production and oxidative status are regulated by mitochondrial Ca2+, we investigated the effect of age on mitochondrial Ca2+ uptake. Although no age-dependent differences were found in Ca2+ uptake kinetics in isolated mitochondria, mitochondrial Ca2+ uptake secondary to SR Ca2+ release was significantly reduced in cardiomyocytes from old hearts, and this effect was associated with decreased NAD(P)H regeneration and increased mitochondrial ROS upon increased contractile activity. Immunofluorescence and proximity ligation assay identified the defective communication between mitochondrial voltage-dependent anion channel and SR ryanodine receptor (RyR) in cardiomyocytes from aged hearts associated with altered Ca2+ handling. Age-dependent alterations in SR Ca2+ transfer to mitochondria and in Ca2+ handling could be reproduced in cardiomyoctes from young hearts after interorganelle disruption with colchicine, at concentrations that had no effect in aged cardiomyocytes or isolated mitochondria. Thus, defective SR-mitochondria communication underlies inefficient interorganelle Ca2+ exchange that contributes to energy demand/supply mistmach and oxidative stress in the aged heart.

Nonautonomous contact guidance signaling during collective cell migration.

Directed migration of groups of cells is a critical aspect of tissue morphogenesis that ensures proper tissue organization and, consequently, function. Cells moving in groups, unlike single cells, must coordinate their migratory behavior to maintain tissue integrity. During directed migration, cells are guided by a combination of mechanical and chemical cues presented by neighboring cells and the surrounding extracellular matrix. One important class of signals that guide cell migration includes topographic cues. Although the contact guidance response of individual cells to topographic cues has been extensively characterized, little is known about the response of groups of cells to topographic cues, the impact of such cues on cell-cell coordination within groups, and the transmission of nonautonomous contact guidance information between neighboring cells. Here, we explore these phenomena by quantifying the migratory response of confluent monolayers of epithelial and fibroblast cells to contact guidance cues provided by grooved topography. We show that, in both sparse clusters and confluent sheets, individual cells are contact-guided by grooves and show more coordinated behavior on grooved versus flat substrates. Furthermore, we demonstrate both in vitro and in silico that the guidance signal provided by a groove can propagate between neighboring cells in a confluent monolayer, and that the distance over which signal propagation occurs is not significantly influenced by the strength of cell-cell junctions but is an emergent property, similar to cellular streaming, triggered by mechanical exclusion interactions within the collective system.