Molecular mechanisms controlling the phenotype and the EMT/MET dynamics of hepatocyte

The complex spatial and paracrine relationships between the various liver histotypes are essential for proper functioning of the hepatic parenchymal cells. Only within a correct tissue organization, in fact, they stably maintain their identity and differentiated phenotype. The loss of histotype identity, which invariably occurs in the primary hepatocytes in culture, or in vivo in particular pathological conditions (fibrosis and tumors), is mainly due to the phenomenon of epithelial-to-mesenchymal transition (EMT). The EMT process, that occurs in the many epithelial cells, appears to be driven by a number of general, non- tissue-specific, master transcriptional regulators. The reverse process, the mesenchymal-to epithelial transition (MET), as yet much less characterized at a molecular level, restores specific epithelial identities, and thus, must include tissue-specific master elements. In this review, we will summarize the so far unveiled events of EMT/MET occurring in liver cells. In particular, we will focus on hepatocyte and describe the pivotal role in the control of EMT/MET dynamics exerted by a tissue-specific molecular mini-circuitry. Recent evidence, indeed, highlighted as two transcriptional factors, the master gene of EMT Snail, and the master gene of hepatocyte differentiation HNF4α, exhorting a direct reciprocal repression, act as pivotal elements in determining opposite cellular outcomes. The different balances between these two master regulators, further integrated by specific microRNAs, in fact, were found responsible for the EMT/METs dynamics as well as for the preservation of both hepatocyte and stem/precursor cells identity and differentiation. Overall these findings impact the maintenance of stem cells and differentiated cells both in in vivo EMT/MET physio-pathological processes as well as in culture.The complex spatial and paracrine relationships between the various liver histotypes are essential for proper functioning of the hepatic parenchymal cells. Only within a correct tissue organization, in fact, they stably maintain their identity and differentiated phenotype. The loss of histotype identity, which invariably occurs in the primary hepatocytes in culture, or in vivo in particular pathological conditions (fibrosis and tumors), is mainly due to the phenomenon of epithelial-to-mesenchymal transition (EMT). The EMT process, that occurs in the many epithelial cells, appears to be driven by a number of general, non- tissue-specific, master transcriptional regulators. The reverse process, the mesenchymal-to epithelial transition (MET), as yet much less characterized at a molecular level, restores specific epithelial identities, and thus, must include tissue-specific master elements. In this review, we will summarize the so far unveiled events of EMT/MET occurring in liver cells. I

Influence of culture on pain comorbidity in women with and without temporomandibular disorder-pain

Evidence on cultural differences in prevalence and impact of common chronic pain conditions, comparing individuals with temporomandibular disorders (TMD) versus individuals without TMD, is limited. The aim was to assess cross-cultural comorbid pain conditions in women with chronic TMD pain. Consecutive women patients (n = 122) with the index condition of chronic TMD pain diagnosed per the research diagnostic criteria for TMD and TMD-free controls (n = 121) matched for age were recruited in Saudi Arabia, Italy and Sweden. Self-report questionnaires assessed back, chest, stomach and head pain for prevalence, pain intensity and interference with daily activities. Logistic regression was used for binary variables, and ancova was used for parametric data analysis, adjusting for age and education. Back pain was the only comorbid condition with a different prevalence across cultures; Swedes reported a lower prevalence compared to Saudis (P 50% due to back pain compared to Italians or Swedes (P < 0·01). Headache was the most common comorbid condition in all three cultures. The total number of comorbid conditions did not differ cross-culturally but were reported more by TMD-pain cases than TMD-free controls (P < 0·01). For both back and head pain, higher average pain intensities (P < 0·01) and interference with daily activities (P < 0·01) were reported by TMD-pain cases, compared to TMD-free controls. Among TMD-pain cases, Italians reported the highest pain-related disability (P < 0·01). Culture influences the associated comorbidity of common pain conditions. The cultural influence on pain expression is reflected in different patterns of physical representation

Delayed-onset muscle soreness does not influence occlusal sensitivity and position sense of the mandible

Masticatory muscle-pain patients often complain about sensorimotor changes, but the effects of pain on the psychophysical properties remain unclear. This study aimed to investigate the effects of delayed-onset muscle soreness (DOMS) on the jaw's position sense (PS) and occlusal sensitivity (OS). In all, 12 participants underwent intense concentric–eccentric jaw exercises. Self-reported muscle fatigue and pain, pain-free maximum mouth opening (MMO), pain pressure thresholds (PPTs) at right and left masseter and right and left anterior temporalis, maximum voluntary bite force (MVBF), PS and OS were recorded before, immediately after, 24 h, 48 h and 1 week after the exercises. Data were analysed with repeated measures anova. Pain and fatigue increased significantly after the exercises, while fatigue also increased 24 h afterwards. Time and site had a significant effect for PPTs, not for MVBF. MMO decreased significantly 24 h after the exercises. OS and PS did not change significantly. Experimentally induced DOMS does not influence the psychophysical properties of the masticatory system

Incidence of temporomandibular joint clicking in adolescents with and without unilateral posterior cross-bite: a 10-year follow-up study

Among different malocclusions, posterior cross-bite is thought to have a strong impact on the correct functioning of the masticatory system. The association between unilateral posterior cross-bite (UPCB) and temporomandibular joint (TMJ) clicking, however, remains still controversial. The aim of this study was to investigate whether the presence of UCPB during early adolescence increases the risk of reporting TMJ clicking after a long-term follow-up. A longitudinal survey design was carried out in a group of 12-year-old young adolescents, who were examined at baseline for TMJ clicking sounds and unilateral posterior cross-bite. After 10 years, 519 subjects could be reached by a telephone survey. Standardised questions were used to collect self-reported TMJ sounds and to determine whether participants had received an orthodontic treatment. Logistic regression analysis revealed a significant association between unilateral posterior cross-bite and subjectively reported TMJ clicking (odds ratio = 6·0; 95% confidence limits = 3·4-10·8; P < 0·0001). The incidence of TMJ clicking was 12%. At a ten-year follow-up, self-reports of TMJ clicking were significantly associated with the presence of UPCB at baseline, but not with the report of having received an orthodontic treatment. Within the limitation of this study, the presence of unilateral posterior cross-bite in young adolescents may increase the risk of reporting TMJ sounds at a 10-year follow-up. The provision of an orthodontic treatment, however, does not appear to reduce the risk of reporting TMJ sounds

Perspectives on next steps in classification of oro-facial pain - part 1: role of ontology

The purpose of this study was to review existing principles of oro-facial pain classifications and to specify design recommendations for a new system that would reflect recent insights in biomedical classification systems, terminologies and ontologies. The study was initiated by a symposium organised by the International RDC/TMD Consortium Network in March 2013, to which the present authors contributed. The following areas are addressed: problems with current classification approaches, status of the ontological basis of pain disorders, insufficient diagnostic aids and biomarkers for pain disorders, exploratory nature of current pain terminology and classification systems, and problems with prevailing classification methods from an ontological perspective. Four recommendations for addressing these problems are as follows: (i) develop a hypothesis-driven classification structure built on principles that ensure to our best understanding an accurate description of the relations among all entities involved in oro-facial pain disorders; (ii) take into account the physiology and phenomenology of oro-facial pain disorders to adequately represent both domains including psychosocial entities in a classification system; (iii) plan at the beginning for field-testing at strategic development stages; and (iv) consider how the classification system will be implemented. Implications in relation to the specific domains of psychosocial factors and biomarkers for inclusion into an oro-facial pain classification system are described in two separate papers

Treatment of Palatally Displaced Canines Using Miniscrews for Direct or Indirect Anchorage: A Three-Dimensional Prospective Cohort Study on Tooth Movement Speed

Palatally impacted canines are usually challenging to treat in terms of both biomechanics and possible side effects. Different therapeutic approaches have been reported with or without the use of temporary anchorage devices, including the canine-first approach. Two groups of patients with palatally impacted canines were compared, observing their canine movement measured on consecutive CBCTs after three months of treatment. In the control group, impacted canines were treated with direct anchorage on miniscrews, and in the test group with indirect anchorage using a miniscrew-supported transpalatal arch. The primary outcome was the canine movement speed; the secondary outcome was the change in the root length of adjacent teeth. The median monthly apex speed was 1.05 mm in the control group (IR [0.74, 1.64]) and 0.72 mm in the test group (IR [0.27, 1.30]). The median monthly cusp displacement was 1.89 mm in the control group (IR [1.04, 2.84]) and 1.08 mm in the test group (IR [0.81, 1.91]). Approximately 50% of teeth adjacent to an impacted canine underwent a negative root length change of less than 1 mm in the majority of cases, but no significant differences were found in root length changes between groups. No statistically significant differences in the reported speeds were found, and no miniscrew failures were observed in either group

Class II functional orthopaedic treatment: a systematic review of systematic reviews

This Systematic Review (SR) aims to assess the quality of SRs and Meta-Analyses (MAs) on functional orthopaedic treatment of Class II malocclusion and to summarise and rate the reported effects. Electronic and manual searches were conducted until June 2014. SRs and MAs focusing on the effects of functional orthopaedic treatment of Class II malocclusion in growing patients were included. The methodological quality of the included papers was assessed using the AMSTAR (Assessment of Multiple Systematic Reviews). The design of the primary studies included in each SR was assessed with Level of Research Design scoring. The evidence of the main outcomes was summarised and rated according to a scale of statements. 14 SRs fulfilled the inclusion criteria. The appliances evaluated were as follows: Activator (2 studies), Twin Block (4 studies), headgear (3 studies), Herbst (2 studies), Jasper Jumper (1 study), Bionator (1 study) and Fränkel-2 (1 study). Four studies reviewed several functional appliances, as a group. The mean AMSTAR score was 6 (ranged 2-10). Six SRs included only controlled clinical trials (CCTs), three SRs included only randomised controlled trials (RCTs), four SRs included both CCTs and RCTs and one SR included also expert opinions. There was some evidence of reduction of the overjet, with different appliances except from headgear; there was some evidence of small maxillary growth restrain with Twin Block and headgear; there was some evidence of elongation of mandibular length, but the clinical relevance of this results is still questionable; there was insufficient evidence to determine an effect on soft tissues

Web-based randomised controlled trials in orthodontics

Randomised controlled trials (RCT) are considered the best source of scientific evidence--the gold standard--when evaluating the efficacy of orthodontic treatments. Frequently, RCT are planned as multicentre trials, with the intention of increasing statistical power and raising the precision of outcome estimates. The management of large-scale RCT, however, requires even more thorough organisation than conventional RCT. Indeed, the need for high accuracy and standardisation in data collection, research aids, secretarial skills, staff and patient training, and organisational meetings, make these studies time-consuming, expensive and, in general, relatively complex to carry out well. A website was developed to support a large scale-orthodontic RCT which aimed to evaluate the efficacy of a functional appliance(www.ortodonzia.unina.it). Websites such as this can increase the quality of data collection, simplify the randomisation process, speed up data collection, and improve trial monitoring. Web-based RCT have the potential to help globalise orthodontic research and also increase our rate of acquisition of evidence in orthodontics