A study on job postures and musculoskeletal illnesses in dentists

Objectives: Musculoskeletal disorders (MSDs) compose a large part of occupational diseases in dental professionals, prevention of which is dependent on assessment and improvement of job postures by means of ergonomic interventions. This study was aimed at evaluation of ergonomic conditions of the profession of dentists and also at assessing the relationship between MSDs and conditions of work. Materials and Methods: This cross-sectional study was performed among 65 dentists using the method of Rapid Entire Body Assessment (REBA). The prevalence of MSDs was obtained by the use of the Nordic Musculoskeletal Questionnaire (NMQ). Results: In this investigation, the prevalence of MSDs for different body parts was: 75.9% for the neck, 58.6% for the shoulders, 56.9% for the upper back, 48.3% for the lower back and 44.8% for the wrist. Job analysis by the use of REBA showed that 89.6% of limbs in group A and 79.3% of limbs in group B had a score > 4. Only neck and lower back pain have significant relationship with the risk levels obtained using the REBA method. Conclusions: It can be concluded that work postures of dentists need to be improved. In addition to education, work station design, rest period during work and regular physical activities should be taken into account

Separating chemotherapy-related developmental neurotoxicity from cytotoxicity in monolayer and neurosphere cultures of human fetal brain cells

Chemotherapy-induced neurotoxicity can reduce the quality of life of patients by affecting their intelligence, senses and mobility. Ten percent of safety-related late-stage clinical failures are due to neurological side effects. Animal models are poor in predicting human neurotoxicity due to interspecies differences and most in vitro assays cannot distinguish neurotoxicity from general cytotoxicity for chemotherapeutics. We developed in vitro assays capable of quantifying the paediatric neurotoxic potential for cytotoxic drugs. Mixed cultures of human fetal brain cells were differentiated in monolayers and as 3D-neurospheres in the presence of non-neurotoxic chemotherapeutics (etoposide, teniposide) or neurotoxicants (methylmercury). The cytotoxic potency towards dividing progenitors versus differentiated neurons and astrocytes was compared using: (1) immunohistochemistry staining and cell counts in monolayers; (2) through quantitative Western blots in neurospheres; and (3) neurosphere migration assays. Etoposide and teniposide, were 5–10 times less toxic to differentiated neurons compared to the mix of all cells in monolayer cultures. In contrast, the neurotoxicant methylmercury did not exhibit selectivity and killed all cells with the same potency. In 3D neurospheres, etoposide and teniposide were 24 to 10 times less active against neurons compared to all cells. These assays can be used prioritise drugs for local drug delivery to brain tumours

Medium- and short-chain dehydrogenase/reductase gene and protein families: The MDR superfamily

The MDR superfamily with ~350-residue subunits contains the classical liver alcohol dehydrogenase (ADH), quinone reductase, leukotriene B4 dehydrogenase and many more forms. ADH is a dimeric zinc metalloprotein and occurs as five different classes in humans, resulting from gene duplications during vertebrate evolution, the first one traced to ~500 MYA (million years ago) from an ancestral formaldehyde dehydrogenase line. Like many duplications at that time, it correlates with enzymogenesis of new activities, contributing to conditions for emergence of vertebrate land life from osseous fish. The speed of changes correlates with function, as do differential evolutionary patterns in separate segments. Subsequent recognitions now define at least 40 human MDR members in the Uniprot database (corresponding to 25 genes when excluding close homologues), and in all species at least 10888 entries. Overall, variability is large, but like for many dehydrogenases, subdivided into constant and variable forms, corresponding to household and emerging enzyme activities, respectively. This review covers basic facts and describes eight large MDR families and nine smaller families. Combined, they have specific substrates in metabolic pathways, some with wide substrate specificity, and several with little known functions

In vitro models of medulloblastoma: choosing the right tool for the job

The recently-defined four molecular subgroups of medulloblastoma have required updating of our understanding of in vitro models to include molecular classification and risk stratification features from clinical practice. This review seeks to build a more comprehensive picture of the in vitro systems available for modelling medulloblastoma. The subtype classification and molecular characterisation for over 40 medulloblastoma cell-lines has been compiled, making it possible to identify the strengths and weaknesses in current model systems. Less than half (18/44) of established medulloblastoma cell-lines have been subgrouped. The majority of the subgrouped cell-lines (11/18) are Group 3 with MYC-amplification. SHH cell-lines are the next most common (4/18), half of which exhibit TP53 mutation. WNT and Group 4 subgroups, accounting for 50% of patients, remain underrepresented with 1 and 2 cell-lines respectively. In vitro modelling relies not only on incorporating appropriate tumour cells, but also on using systems with the relevant tissue architecture and phenotype as well as normal tissues. Novel ways of improving the clinical relevance of in vitro models are reviewed, focusing on 3D cell culture, extracellular matrix, co-cultures with normal cells and organotypic slices. This paper champions the establishment of a collaborative online-database and linked cell-bank to catalyse preclinical medulloblastoma research

Muscle-type creatine kinase interacts with central domains of the M-band proteins myomesin and M-protein

Muscle-type creatine kinase (MM-CK) is a member of the CK isoenzyme family with key functions in cellular energetics. MM-CK interacts in an isoform-specific manner with the M-band of sarcomeric muscle, where it serves as an efficient intramyofibrillar ATP-regenerating system for the actin-activated myosin ATPase located nearby on both sides of the M-band. Four MM-CK-specific and highly conserved lysine residues are thought to be responsible for the interaction of MM-CK with the M-band. A yeast two-hybrid screen led to the identification of MM-CK as a binding partner of a central portion of myomesin (My7-8). An interaction was observed with domains six to eight of the closely related M-protein but not with several other Ig-like domains, including an M-band domain, of titin. The observed interactions were corroborated and characterised in detail by surface plasmon resonance spectroscopy (BiaCore). In both cases, they were CK isoform-specific and the MM-CK-specific lysine residues (K8. K24, K104 and K115) are involved in this interaction. At pH 6.8, the dissociation constants for the myomesin/MM-CK and the M-protein/MM-CK binding were in the range of 50-100 nM and around 1 microM, respectively. The binding showed pronounced pH-dependence and indicates a dynamic association/dissociation behaviour, which most likely depends on the energy state of the muscle. Our data propose a simple model for the regulation of this dynamic interaction

Ponsin interacts with Nck adapter proteins: implications for a role in cytoskeletal remodelling during differentiation of skeletal muscle cells

Skeletal muscle differentiation is a complex process: It is characterised by changes in gene expression and protein composition. Simultaneously, a dramatic remodelling of the cytoskeleton and associated cell-matrix contacts, the costameres, occurs. The expression and localisation of the protein ponsin at cell-matrix contacts marks the establishment of costameres. In this report we show that skeletal muscle cells are characterised by a novel ponsin isoform, which contains a large insertion in its carboxy-terminus. This skeletal muscle-specific module binds the adapter proteins Nck1 and Nck2, and increased co-localisation of ponsin with Nck2 is observed at remodelling cell-matrix contacts of differentiating skeletal muscle cells. Since this ponsin insertion can be phosphorylated, it may adjust the interaction affinity with Nck adapter proteins. The novel ponsin isoform and its interaction with Nck1/2 provide exciting insight into the convergence of signalling pathways at the costameres, and its crucial role for skeletal muscle differentiation and re-generation