Editorial to the Special Issue "The Effect of Exercise Intensity and Psychological Intervention on Musculoskeletal Disorders".

Musculoskeletal disorders are responsible for the most prevalent form of pain, and necessitate a comprehensive approach to rehabilitation [...].

Evaluation of the diagnostic ability of oral lesions on clinical images among undergraduate dental students.

INTRODUCTION: The dentist should be able to carry out systematic oral examinations of the mucosa of patients in order to diagnose any alterations at an early stage. MATERIALS AND METHODS: An observational, analytical, prospective, and longitudinal study was carried out. 161 students were evaluated at the beginning of their clinical practice in their 4th year of dental school (September 2019), at the beginning and at the end of their 5th year of dental school (June 2021). Thirty oral lesions were projected, and the students were asked to provide an answer; if the lesions were benign, malignant, or potentially malignant, whether they should be biopsied and/or treated and a presumptive diagnosis. RESULTS: Significant improvement (p < .001) was obtained between the 2019 and 2021 results, in relation to the classification, need for biopsy and treatment of lesions. For differential diagnosis, no significant difference (p = .985) was obtained between the 2019 and 2021 responses. Malignant lesions and PMD obtained mixed results, with the best results corresponding to OSCC. DISCUSSION: In this study, a correct lesion classification by the students was over 50%. As for the OSCC, the results were superior to the rest of the images, reaching more than 95% correct. CONCLUSION: Theoretical-practical training from universities and continuing education for graduates in relation to oral mucosal pathologies should be further promoted.

Salivary biomarkers in burning mouth syndrome: A systematic review and meta-analysis.

The objective of this systematic review was to evaluate which salivary biomarkers are altered in patients with burning mouth syndrome (BMS) compared to a control group (CG). A comprehensive literature search was conducted in four databases. Case-control studies evaluating salivary biomarkers in BMS patients were included. Risk of bias was assessed using the Newcastle-Ottawa tool. RevMan was used for meta-analysis. Seventeen studies were selected. The included studies collected 54 different biomarkers. Of these biomarkers, only three (cortisol, α-amylase, and dehydroepiandrosterone) were analyzed in three or more studies. Dehydroepiandrosterone obtained contradictory results among the studies. However, cortisol and α-amylase levels were found to be higher in BMS patients. Cortisol was the only biomarker which could be included for meta-analysis. Cortisol levels were significantly higher in the BMS group compared to the CG (Mean Difference = 0.39; 95% CI [0.14-0.65]; p = 0.003). In conclusion, different studies investigated salivary biomarkers in patients with BMS compared to a CG, with controversial results. Meta-analysis, confirmed by trial-sequential analysis, showed how cortisol levels were significantly higher in BMS. Cortisol emerges as an interesting salivary biomarker in BMS, but future properly designed studies are needed to evaluate its role in diagnosis and/or response to treatment.

Association between Sleep Disorders and Sleep Quality in Patients with Temporomandibular Joint Osteoarthritis: A Systematic Review.

BACKGROUND: Osteoarthritis (OA) is a leading cause of disability, the most common form of chronic disease in the temporomandibular joint (TMJ), and the most severe disease type of temporomandibular disorders (TMD). The etiology of TMD is multifactorial, considering parafunctional habits, sleep bruxism, or sleep disturbance as common factors. Insomnia and apnea are the two most frequent forms of sleep disorders in TMD patients. Due to this, the objective of this systematic review was to highlight whether there is currently scientific evidence in the literature describing that patients with temporomandibular joint osteoarthritis (TMJ-OA) are associated with increased sleep disorders or impaired sleep quality. METHODS: This systematic review was completed in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) statement and was registered with PROSPERO prior to completion of the main search. Original observational studies that analyze the association of sleep disorders and sleep quality in patients with TMJ-OA were included in the present review. RESULTS: 770 studies were screened by abstract and title according to inclusion and exclusion criteria, and finally, 7 articles were included in the qualitative synthesis and a total of 772 patients diagnosed with TMJ-OA. CONCLUSIONS: There is insufficient evidence to indicate that patients with TMJ OA are associated with increased sleep disorders or poorer sleep quality.

Adaptation of clinical subjects in Dentistry to virtual environments during the COVID-19 pandemic in a Spanish University: A case study.

INTRODUCTION: The evolution of the pandemic has generated a crisis in all areas, also including the faculties of dentistry. We detail how the teaching guides for clinical subjects have been adapted in the Department of Clinical Dentistry at the Universidad Europea of Madrid, moving to a 100% online environment. USUAL DEVELOPMENT OF CLINICAL PRACTICES IN THE DDS DEGREE OF UEM: Students in the fourth and fifth year of DDS degree take the courses "Introduction to Clinical Practice" and "Supervised Practice." Within the framework of continuous assessment, different systems and procedures are used to evaluate knowledge, skills or competences. CURRICULAR ADAPTATION DURING THE PERIOD OF THE COVID-19 PANDEMIC: It was necessary to adapt the practical contents to virtual contents. 35% of the course (12 weeks) was adapted to a 100% online environment. Several activities were carried out that could be evaluated in real time, including lectures, clinical cases and resolution of multidisciplinary dental treatments. DEVELOPMENT OF CLINICAL PRACTICES IN HEALTH EDUCATION IN OTHER INSTITUTIONS DURING THE PANDEMIC: A narrative review was conducted to identify how this situation has been addressed in other institutions and countries; finding that similarly, it has been possible to establish monitoring of clinical practices in a virtual environment. An online questionnaire was conducted to the fourth and fifth year students of DDS degree to stablish the acceptance of the adaptation during the pandemic. CONCLUSION: Despite the limitations of online training for the development of clinical practice, a system has been established to ensure appropriate clinical training for undergraduate students in dentistry. Some of the developments were well accepted by the students.

Efficacy of botulinum toxin type A in the management of masticatory myofascial pain: A retrospective clinical study.

BACKGROUND: Muscular pain is the main cause of disability worldwide. Myofascial pain of orofacial origin is a frequent condition, the treatment of which is not always accomplished with traditional treatment. Botulinum toxin type A (BTA) is being studied for the treatment of this type of pain with contradicting results. Thus, the objective of this study was to assess the efficacy of BTA in the therapeutic management of masticatory myofascial pain (MFP). CASE DESCRIPTION: A retrospective study of 100 patients with a diagnosis of MFP was conducted. The control group (50 patients) received conventional treatment (prescription of a muscle relaxant and craniocervical physical therapy). The BTA group (50 patients) received this same treatment and the infiltration of 100 units of BTA in the masticatory musculature. Subjective and objective pain ratings and range of mandibular movements were recorded before and after the treatment. No differences were found between groups in the baseline values. Statistically significant improvements were found in both groups compared with baseline values in all studied parameters. Moreover, BTA improved the subjective pain ratings compared with the control group. The administration of BTA added to the conventional treatment does not seem to improve objective pain ratings and functional measurements, but it improves the subjective pain ratings. PRACTICAL IMPLICATIONS: The addition of BTA could be beneficial in the treatment of MFP in addition to conventional treatment, but further studies are needed to elucidate the mechanisms underlying this positive effect.

Effects of photobiomodulation with low-level laser therapy in burning mouth syndrome: A randomized clinical trial.

BACKGROUND: Photobiomodulation (PBM) has proven to be effective in different painful conditions. OBJECTIVES: To assess the effect of photobiomodulation for pain management in burning mouth syndrome (BMS) patients, besides analysing the impact on different aspects of quality of life. METHODS: A randomized, single-blind, clinical trial was performed among 20 patients with BMS. Photobiomodulation was applied in the study group (n = 10) with a dose of 12 J/cm2 during 10 sessions, comparing with a placebo group (n = 10) with the laser turned off. Pain was assessed using the visual analogue scale (VAS) before starting each treatment session, and at the 1-month and 4-month follow-up appointments. Some validated questionnaires for general health were also complete: SF-36, OHIP-14, Epworth, SCL 90-R and McGill. RESULTS: All patients (n = 10) in the study group improved their pain ending treatment and remaining among 90% (n = 9) in the 4-month follow-up. Significant improvement was found in the study group in some sections of McGill questionnaire, Epworth scale, and SCL 90-R at the end of the treatment and in the 1-month and 4-month follow-ups. CONCLUSIONS: Photobiomodulation seems to be effective in reducing pain in patients with BMS, as well as, having a positive impact on the psychological state of these patients.

General health status of a sample of patients with burning mouth syndrome: A case-control study.

BACKGROUND: The relationship of burning mouth syndrome (BMS) with possible alterations in patients' general health has been subject of study and controversy during the last years. OBJECTIVE: To analyse the general health status of patients with BMS, comparing it with a control group. METHODS: A case-control study was conducted to compare the diseases, medications, blood test alterations, disturbances in general health, oral quality of life, xerostomia, sleep quality and psychological status between a group of 20 patients with BMS and a group of 40 patients who did not suffer from this disease. RESULTS: BMS patients suffered more comorbidities and consumed more medications than controls. More mental, behavioural or neurodevelopmental disorders in BMS patients were found, consuming more drugs for nervous and cardiovascular systems, and alimentary tract and metabolism. Lower levels of iron and higher levels of folic acid were found in BMS patients compared to controls. General health status, oral health impact, sleepiness, psychological status and xerostomia levels were also significantly worsened in BMS patients than in controls. CONCLUSIONS: BMS patients presented a worsened health status over controls suffering more comorbidities, consuming more medications and showing adverse results in all the health variables analysed in this study.

Efficacy of Low-Level Laser Therapy for the Therapeutic Management of Neuropathic Orofacial Pain: A Systematic Review.

AIMS: To evaluate the efficacy of low-level laser therapy (LLLT) for the therapeutic management of neuropathic orofacial pain. METHODS: This systematic review was conducted according to PRISMA guidelines. A comprehensive search of the literature was conducted in the PubMed/MEDLINE, Scopus, and Cochrane Library databases up to March 8, 2018, using terms such as low-level laser therapy, neuropathic pain, orofacial pain, neuralgia, neuropathy, and all the entities described in section 13 of the International Classification of Headache Disorders, third edition. The primary outcome was measurement of pain intensity. RESULTS: A total of 997 studies were obtained with the initial search; 13 (8 randomized controlled trials, 2 prospective studies, and 3 case series) met the inclusion criteria and were analyzed for data extraction. Three provided data for the treatment of trigeminal neuralgia, 1 for occipital neuralgia, and 10 for burning mouth syndrome. All studies showed a reduction in pain intensity (most of them significant). The different studies analyzed LLLT alone and compared to placebo, to another treatment, or to different LLLT application protocols. CONCLUSION: LLLT seems to be effective as a treatment option for different neuropathic orofacial pain entities such as trigeminal neuralgia, occipital neuralgia, and burning mouth syndrome as a single or combined treatment. However, more quality studies assessing all outcome measures of chronic pain are needed in the medium and long terms. Furthermore, due to the lack of standardization of the application technique, more well-designed studies are required to confirm the results of this systematic review.

The peptidoglycan and biofilm matrix of Staphylococcus epidermidis undergo structural changes when exposed to human platelets.

Staphylococcus epidermidis is a bacterium frequently isolated from contaminated platelet concentrates (PCs), a blood product used to treat bleeding disorders in transfusion patients. PCs offer an accidental niche for colonization of S. epidermidis by forming biofilms and thus avoiding clearance by immune factors present in this milieu. Using biochemical and microscopy techniques, we investigated the structural changes of the peptidoglycan (PG) and the biofilm matrix of S. epidermidis biofilms formed in whole-blood derived PCs compared to biofilms grown in glucose-supplemented trypticase soy broth (TSBg). Both, the PG and the biofilm matrix are primary mechanisms of defense against environmental stress. Here we show that in PCs, the S. epidermidis biofilm matrix is mainly of a proteinaceous nature with extracellular DNA, in contrast to the predominant polysaccharide nature of the biofilm matrix formed in TSBg cultures. PG profile studies demonstrated that the PG of biofilm cells remodels during PC storage displaying fewer muropeptides variants than those observed in TSBg. The PG muropeptides contain two chemical modifications (amidation and O-acetylation) previously associated with resistance to antimicrobial agents by other staphylococci. Our study highlights two key structural features of S. epidermidis that are remodeled when exposed to human platelets and could be used as targets to reduce septic transfusions events.

Effects of Xerostom® products on xerostomia in primary Sjögren's syndrome: A randomized clinical trial.

OBJECTIVES: To assess the effects of Xerostom® toothpaste and mouthwash in primary Sjögren's syndrome (pSS) patients with xerostomia. SUBJECTS AND METHODS: A double-blinded, randomized study where patients were assigned at baseline test or control products. Patients used the products 3 times/day/28 days. We used a visual analogue scale (VAS) for xerostomia and an Oral Health Impact Profile-14 (OHIP-14), baseline and after treatment, to assess possible improvement. RESULTS: A total of 28 patients with pSS were included in this study, but only 24 finished it (all women, mean age 55.21 ± 11.87), and 13 patients received the test and 11 the control. VAS and OHIP-14 scores decreased in both groups after treatment but significant differences between groups were not found. We do not detect VAS intragroup significant differences before and after treatment in test and control groups. A significant improvement in OHIP-14 was identified in the treatment group, while no significant differences were observed in the control group. No adverse effects were present. CONCLUSIONS: Xerostom® toothpaste and mouthrinse may alleviate and improve quality of life without associated side effects, but further research with a larger number of participants and follow-up are necessary to establish the positive efficacy of these topical products in pSS patients.

Bacterial secretion of D-arginine controls environmental microbial biodiversity.

Bacteria face tough competition in polymicrobial communities. To persist in a specific niche, many species produce toxic extracellular effectors to interfere with the growth of nearby microbes. These effectors include the recently reported non-canonical D-amino acids (NCDAAs). In Vibrio cholerae, the causative agent of cholera, NCDAAs control cell wall integrity in stationary phase. Here, an analysis of the composition of the extracellular medium of V. cholerae revealed the unprecedented presence of D-Arg. Compared with other D-amino acids, D-Arg displayed higher potency and broader toxicity in terms of the number of bacterial species affected. Tolerance to D-Arg was associated with mutations in the phosphate transport and chaperone systems, whereas D-Met lethality was suppressed by mutations in cell wall determinants. These observations suggest that NCDAAs target different cellular processes. Finally, even though virtually all Vibrio species are tolerant to D-Arg, only a few can produce this D-amino acid. Indeed, we demonstrate that D-Arg may function as part of a cooperative strategy in vibrio communities to protect non-producing members from competing bacteria. Because NCDAA production is widespread in bacteria, we anticipate that D-Arg is a relevant modulator of microbial subpopulations in diverse ecosystems.

Determinants of Bacterial Morphology: From Fundamentals to Possibilities for Antimicrobial Targeting.

Bacterial morphology is extremely diverse. Specific shapes are the consequence of adaptive pressures optimizing bacterial fitness. Shape affects critical biological functions, including nutrient acquisition, motility, dispersion, stress resistance and interactions with other organisms. Although the characteristic shape of a bacterial species remains unchanged for vast numbers of generations, periodical variations occur throughout the cell (division) and life cycles, and these variations can be influenced by environmental conditions. Bacterial morphology is ultimately dictated by the net-like peptidoglycan (PG) sacculus. The species-specific shape of the PG sacculus at any time in the cell cycle is the product of multiple determinants. Some morphological determinants act as a cytoskeleton to guide biosynthetic complexes spatiotemporally, whereas others modify the PG sacculus after biosynthesis. Accumulating evidence supports critical roles of morphogenetic processes in bacteria-host interactions, including pathogenesis. Here, we review the molecular determinants underlying morphology, discuss the evidence linking bacterial morphology to niche adaptation and pathogenesis, and examine the potential of morphological determinants as antimicrobial targets.

Ultra-Sensitive, High-Resolution Liquid Chromatography Methods for the High-Throughput Quantitative Analysis of Bacterial Cell Wall Chemistry and Structure.

High-performance liquid chromatography (HPLC) analysis has been critical for determining the structural and chemical complexity of the cell wall. However this method is very time consuming in terms of sample preparation and chromatographic separation. Here we describe (1) optimized methods for peptidoglycan isolation from both Gram-negative and Gram-positive bacteria that dramatically reduce the sample preparation time, and (2) the application of the fast and highly efficient ultra-performance liquid chromatography (UPLC) technology to muropeptide separation and quantification. The advances in both analytical instrumentation and stationary-phase chemistry have allowed for evolved protocols which cut run time from hours (2-3 h) to minutes (10-20 min), and sample demands by at least one order of magnitude. Furthermore, development of methods based on organic solvents permits in-line mass spectrometry (MS) of the UPLC-resolved muropeptides. Application of these technologies to high-throughput analysis will expedite the better understanding of the cell wall biology.

Chemometric Analysis of Bacterial Peptidoglycan Reveals Atypical Modifications That Empower the Cell Wall against Predatory Enzymes and Fly Innate Immunity.

Peptidoglycan is a fundamental structure for most bacteria. It contributes to the cell morphology and provides cell wall integrity against environmental insults. While several studies have reported a significant degree of variability in the chemical composition and organization of peptidoglycan in the domain Bacteria, the real diversity of this polymer is far from fully explored. This work exploits rapid ultraperformance liquid chromatography and multivariate data analysis to uncover peptidoglycan chemical diversity in the Class Alphaproteobacteria, a group of Gram negative bacteria that are highly heterogeneous in terms of metabolism, morphology and life-styles. Indeed, chemometric analyses revealed novel peptidoglycan structures conserved in Acetobacteria: amidation at the α-(l)-carboxyl of meso-diaminopimelic acid and the presence of muropeptides cross-linked by (1-3) l-Ala-d-(meso)-diaminopimelate cross-links. Both structures are growth-controlled modifications that influence sensitivity to Type VI secretion system peptidoglycan endopeptidases and recognition by the Drosophila innate immune system, suggesting relevant roles in the environmental adaptability of these bacteria. Collectively our findings demonstrate the discriminative power of chemometric tools on large cell wall-chromatographic data sets to discover novel peptidoglycan structural properties in bacteria.

A novel peptidoglycan D,L-endopeptidase induced by Salmonella inside eukaryotic cells contributes to virulence.

Bacteria remodel peptidoglycan structure in response to environmental changes. Many enzymes are involved in peptidoglycan metabolism; however, little is known about their responsiveness in a defined environment or the modes they assist bacteria to adapt to new niches. Here, we focused in peptidoglycan enzymes that intracellular bacterial pathogens use inside eukaryotic cells. We identified a peptidoglycan enzyme induced by Salmonella enterica serovar Typhimurium in fibroblasts and epithelial cells. This enzyme, which shows γ-D-glutamyl-meso-diaminopimelic acid D,L-endopeptidase activity, is also produced by the pathogen in media with limited nutrients and in resting conditions. The enzyme, termed EcgA for endopeptidase responding to cessation of growth', is encoded in a S. Typhimurium genomic island absent in Escherichia coli. EcgA production is strictly dependent on the virulence regulator PhoP in extra- and intracellular environments. Consistent to this regulation, a mutant lacking EcgA is attenuated in the mouse typhoid model. These findings suggest that specialised peptidoglycan enzymes, such as EcgA, might facilitate Salmonella adaptation to the intracellular lifestyle. Moreover, they indicate that readjustment of peptidoglycan metabolism inside the eukaryotic cell is essential for host colonisation.

High-throughput, Highly Sensitive Analyses of Bacterial Morphogenesis Using Ultra Performance Liquid Chromatography.

The bacterial cell wall is a network of glycan strands cross-linked by short peptides (peptidoglycan); it is responsible for the mechanical integrity of the cell and shape determination. Liquid chromatography can be used to measure the abundance of the muropeptide subunits composing the cell wall. Characteristics such as the degree of cross-linking and average glycan strand length are known to vary across species. However, a systematic comparison among strains of a given species has yet to be undertaken, making it difficult to assess the origins of variability in peptidoglycan composition. We present a protocol for muropeptide analysis using ultra performance liquid chromatography (UPLC) and demonstrate that UPLC achieves resolution comparable with that of HPLC while requiring orders of magnitude less injection volume and a fraction of the elution time. We also developed a software platform to automate the identification and quantification of chromatographic peaks, which we demonstrate has improved accuracy relative to other software. This combined experimental and computational methodology revealed that peptidoglycan composition was approximately maintained across strains from three Gram-negative species despite taxonomical and morphological differences. Peptidoglycan composition and density were maintained after we systematically altered cell size in Escherichia coli using the antibiotic A22, indicating that cell shape is largely decoupled from the biochemistry of peptidoglycan synthesis. High-throughput, sensitive UPLC combined with our automated software for chromatographic analysis will accelerate the discovery of peptidoglycan composition and the molecular mechanisms of cell wall structure determination.

Structural constraints and dynamics of bacterial cell wall architecture.

The peptidoglycan wall (PG) is a unique structure which confers physical strength and defined shape to bacteria. It consists of a net-like macromolecule of peptide interlinked glycan chains overlying the cell membrane. The structure and layout of the PG dictates that the wall has to be continuously modified as bacteria go through division, morphological differentiation, and adaptive responses. The PG is poorly known in structural terms. However, to understand morphogenesis a precise knowledge of glycan strand arrangement and of local effects of the different kinds of subunits is essential. The scarcity of data led to a conception of the PG as a regular, highly ordered structure which strongly influenced growth models. Here, we review the structure of the PG to define a more realistic conceptual framework. We discuss the consequences of the plasticity of murein architecture in morphogenesis and try to define a set of minimal structural constraints that must be fulfilled by any model to be compatible with present day information.