Chronic melatonin treatment improves obesity by inducing uncoupling of skeletal muscle SERCA-SLN mediated by CaMKII/AMPK/PGC1α pathway and mitochondrial biogenesis in female and male Zücker diabetic fatty rats.

Melatonin acute treatment limits obesity of young Zücker diabetic fatty (ZDF) rats by non-shivering thermogenesis (NST). We recently showed melatonin chronically increases the oxidative status of vastus lateralis (VL) in both obese and lean adult male animals. The identification of VL skeletal muscle-based NST by uncoupling of sarcoendoplasmic reticulum Ca2+-ATPase (SERCA)- sarcolipin (SLN) prompted us to investigate whether melatonin is a SERCA-SLN calcium futile cycle uncoupling and mitochondrial biogenesis enhancer. Obese ZDF rats and lean littermates (ZL) of both sexes were subdivided into two subgroups: control (C) and 12 weeks orally melatonin treated (M) (10 mg/kg/day). Compared to the control groups, melatonin decreased the body weight gain and visceral fat in ZDF rats of both sexes. Melatonin treatment in both sex obese rats restored the VL muscle skin temperature and sensitized the thermogenic effect of acute cold exposure. Moreover, melatonin not only raised SLN protein levels in the VL of obese and lean rats of both sexes; also, the SERCA activity. Melatonin treatment increased the SERCA2 expression in obese and lean rats (both sexes), with no effects on SERCA1 expression. Melatonin increased the expression of thermogenic genes and proteins (PGC1-α, PPARγ, and NRF1). Furthermore, melatonin treatment enhanced the expression ratio of P-CaMKII/CaMKII and P-AMPK/AMPK. In addition, it rose mitochondrial biogenesis. These results provided the initial evidence that chronic oral melatonin treatment triggers the CaMKII/AMPK/PGC1α axis by upregulating SERCA2-SLN-mediated NST in ZDF diabetic rats of both sexes. This may further contribute to the body weight control and metabolic benefits of melatonin.

Adapting evaluation method of skills acquisition in basic cardiopulmonary resuscitation among year 5 and year 6 primary school pupils during the COVID-19 lockdown: a pilot study.

OBJECTIVE: This longitudinal descriptive study aimed to evaluate cognitive skills acquisition in basic Cardiopulmonary Resuscitation (bCPR) among a group of Year 5 and Year 6 primary school pupils. The study made use of online tools due to the impossibility of conventional methods during the COVID-19 lockdown. MATERIALS AND METHODS: Pupils received formal training in bCPR. Training was imparted uniformly by a teacher at the school (qualified in Basic Life Support -BLS- and Advanced Life Support -ALS- training by the CPR National Plan). The skills acquired (those proposed as essential for bCPR training by the European Resuscitation Council) were evaluated fifteen weeks later. Skills acquisition was evaluated by means of an online questionnaire developed specifically for the study. RESULTS: In all the cognitive skills included in bCPR training, the acquisition level achieved was over 65%. Acquisition of knowledge of the anatomical areas at which cardiac massage must be applied and the means of emergency systems activation was high, while 25.5% of pupils knew the order in which maneuvers should be performed. Pupils' self-confidence and self-perception of their capacity to act when faced with a real CPR situation increased significantly. CONCLUSIONS: Primary school pupils learned all the cognitive skills involved in bCPR, showing high levels of skills acquisition and positive self-perception of their capacity to apply them.

Pseudomembranous oral candidiasis resolved with a mouthwash containing 0.05% chlorhexidine + 0.05% cetylpyridinium chloride.

A 50-year-old woman was referred to the clinic reporting oral discomfort during the previous month and plaques of a white removable slough. Diagnosis of pseudomembranous oral candidiasis was clinically confirmed. When the tongue and palatal mucosa were wiped with gauze, the soft yellowish-white slough detached revealing the erythematous surface beneath. The patient also presented paranoid schizophrenia and severe depression, pulmonary emphysema, and two vertebral hernias. She was a smoker (10 cigarettes per day) with xerostomia that was being treated with: bupropion, reboxetine, quetiapine, trazadone clotiapine, pregabalin, fentanyl (patches), and alprazolam. To minimize the risk of potential drug interactions, a mouthwash containing 0.05% chlorhexidine + 0.05% cetylpyridinium chloride was prescribed three times a day for two weeks. At the end of the two weeks, the candidiasis had abated.

Disease-Modifying Antirheumatic Drugs (DMARDs) and drug interactions in dentistry.

OBJECTIVE: Rheumatoid arthritis is a chronic autoimmune disease. Treatment aims to reduce and improve its signs and symptoms. Hence, Disease-Modifying Antirheumatic Drugs (DMARDs) are the treatment of choice. The objective of this study was to identify potential interactions between DMARDs and the drugs most frequently prescribed in dentistry in order to avoid adverse reactions. MATERIALS AND METHODS: This literature review sets out to define possible adverse reactions provoked by pharmacological interactions between DMARDs and the drugs commonly prescribed in dentistry. A search was conducted in PubMed by searching the names of drugs used in dentistry, "drug interactions," "rheumatoid arthritis," and "dentistry", "hydroxychloroquine", "leflunomide", "methotrexate", "sulfasalazine", "adalimumab", "anakinra", "etanercept", "abatacept", "infliximab" and "rituximab". RESULTS: It was found that most DMARDs show potential interactions with many drugs used in dentistry, including various antibiotics, analgesics, anesthetics, antifungals, and corticosteroids. CONCLUSIONS: It is clinically important for oral health clinicians to be aware of possible drug interactions between DMARDs and the drugs commonly prescribed in dentistry to prevent potential adverse reactions and avoid endangering the patient.

Remdesivir-COVID-19: drug interactions in dentistry.

OBJECTIVE: Remdesivir is a nucleotide analogue prodrug that inhibits viral RNA polymerases. It has been recognized recently as a promising antiviral drug against a wide array of RNA viruses (including SARS/MERS-CoV5). We aimed at determining which drugs used in dentistry interact with Remdesivir in order to avoid adverse reactions that may worsen the condition of patients with COVID-19. MATERIALS AND METHODS: A literature review was conducted to identify potential drug interactions between remdesivir (used in the treatment of COVID-19) and drugs prescribed in dentistry. The search was made in the databases PubMed and MEDLINE and official websites using key terms remdesivir, drug interactions and dentistry for articles published up to 31st July 2020. RESULTS: According to the articles reviewed, a total of 279 drugs interact with Remdesivir. Two major interactions have been reported, 277 moderate drug interactions, and one with alcohol/food. The drug interactions involving drugs prescribed in dentistry are all moderate drug interactions and are (according to drug group): (1) antibiotics: azithromycin, clavulanate, doxycycline, erythromycin, levofloxacin; (2) antifungals: clotrimazole, fluconazole, itraconazole, ketoconazole; (3) non-steroidal anti-inflammatories (NAIDS): celecoxib diclofenac, etodolac, flurbiprofen, ibuprofen, ketoprofen, ketorolac, mefenamic acid, naproxen, piroxicam. CONCLUSIONS: It is clinically necessary for oral health professionals to be aware of possible drug interactions that may occur between remdesivir and drugs commonly prescribed in dentistry in order to prevent adverse reactions that may even endanger the life of a patient with COVID-19.

Pharmacogenomics in medication-related osteonecrosis of the jaw: a systematic literature review.

OBJECTIVE: Medication-related osteonecrosis of the jaw (ONJ) is an adverse, severe and debilitating effect, which although infrequent, affects patients with osteoporosis or neoplasm who take bisphosphonates, antiresorptive drugs, and/or antiangiogenic drugs. Its etiopathogenesis is unknown, although genetic causes have been postulated. MATERIALS AND METHODS: This review analyzed articles published to date that have studied genetic factors associated with ONJ. Fifteen case-control studies were included, published between 2008 and 2018. RESULTS: Five set out to determine genetic causes by means of genome-centered techniques, while ten do so by investigating gene-centered variants. Nine works found statistically significant associations between one or various single nucleotide polymorphisms (SNPs) and the appearance of ONJ. None of the studies coincided as to which genes present some association. CONCLUSIONS: The review observed the moderate impact of genetic factors on the appearance of ONJ. It also showed the heterogeneity of the studies that have investigated ONJ to date. In future studies, involving international and interhospital collaboration will be necessary to recruit sample sizes of sufficient size, elaborate adequate study designs, obtain clear results, and advance our understanding of ONJ and make it possible to single out individual patients at risk.

Resolution of a case of denosumab-related osteonecrosis of the jaw after tooth extraction.

Denosumab is an antiresorptive drug that blocks osteoclast maturation, function and survival, improving bone mineral density and reducing the probability of fracture. It has adverse effects and can be the cause of hypocalcemia and osteonecrosis of the jaw. This report describes the case of a 59-year-old woman with hypothyroidism, antecedents of breast cancer, two strokes, and severe bone osteoporosis. Extraction of tooth 3.6 was performed, and within a month she was administered with a denosumab injection. One month later maxillary osteonecrosis appeared in the lingual distal area of the extraction site. Four months later the case was resolved by means of non-surgical treatment.

WITHDROWN: Effect of smoking habit on crestal bone height in maxillary sinus augmentation with bone grafts.

In relation to the article with reference "Carreño-Carreño J, Gómez-Moreno G, Aguilar-Salvatierra A, Menéndez-López-Mateos C, Piattelli A, Menéndez-Núñez M. Effect of smoking habit on crestal bone height in maxillary sinus augmentation with bone grafts. Med Oral Patol Oral Cir Bucal. (2018), doi:10.4317/medoral.22439", published in Oral Medicine Oral Pathology and Oral Surgery in the modality "AHEAD OF PRINT - article in press", the authors mention that "The study was conducted according to the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) Statement". However, and based on the opinion of several expert reviewers who have re-evaluated the article, it is considered that although "there has not been plagiarism", these STROBE criteria are not adequately met. In addition, the mentioned article is very similar to two articles that have already been published by the same authors in Clinical Oral Implants Research. The sample is the same; many data are repeated; and the only difference is the inclusion of a variable (smoking), which does not exert a significant effect. This outcome therefore would not justify publication of the paper in the journal. Retraction of the article is therefore decided.

Comparing student and staff perceptions of the "Educational Climate" in Spanish Dental Schools using the Dundee Ready Education Environment Measure.

OBJECTIVE: To compare the perceptions of students and teachers of the "Educational Climate" (EC) in Spanish public dental schools. METHODS: A group of 1064 students and 354 teachers from six Spanish public dental schools responded to the DREEM questionnaire. This has 50 items grouped into five subscales: perception of learning (Learning); perception of teachers (Teachers); academic self-perceptions (Academic); perception of the atmosphere in the faculty (Atmosphere); and social self-perceptions (Social). The DREEM scale provides results for each item, each subscale and the overall EC. RESULTS: The EC scores were 123.2 (61.6%) for the students and 134.1 (67.0%) for the teachers (P<.001). The scores of the students and teachers for the subscales were, respectively: 27.9 (58.1%) and 30.2 (63.0 %) for Learning (P<.001); 26.8 (60.9%) and 32.6 (74.1%) for Teachers (P<.001); 20.7 (64.7%) and 20.5 (64.0%) for Academic (P=.333); 29.9 (62.3%) and 33.7 (70.3%) for Atmosphere (P<.001); and 17.9 (64.0%) and 16.9 (60.5%) for Social (P<.001). The students identified six problematic items (12.0 %) compared to only two (4.0 %) highlighted by the teachers. CONCLUSION: The students and teachers considered the EC to be "more positive than negative" in Spanish public dental schools; and the different subscales to be "positive and acceptable." The teachers did, however, evaluate the EC, and specifically the learning-teaching process, more positively than their students, identifying fewer problematic educational aspects. Both groups agreed on the need to: improve support systems for students who suffer from stress and reduce teaching based on "factual learning."

Drug-related oral malodour (halitosis): a literature review.

Dry mouth (xerostomia), is a fairly common, well-researched condition, which is an indirect cause of oral malodour. This systematic literature review looked into another cause of bad breath: adverse drug reactions in the orofacial region causing halitosis. The study focused on extraoral halitosis, and its subdivisions, particularly blood borne halitosis in which malodourous compounds in the blood stream are carried to the lungs, passively diffused across the pulmonary alveolar membrane to enter the breath. An electronic search was conducted in various databases. Inclusion criteria were: editorials, case control studies, retrospective studies and randomized double-blind studies published in English between 1983 and March 2017. The search identified a total of 23 articles. According to these, drug-related halitosis may be caused by nine medications. Dimethyl sulfoxide, cysteamine and suplatast tosilate are metabolised to dimethyl sulfide, a malodourous compound that is stable in blood and is transported into the breath. Disulfiram is reduced to carbon disulfide, also a stable compound in blood. Nitric oxide reacts with foul-smelling volatile organosulfur compounds. The degradation of penicillamine raises the pH level, favouring the growth of gram-negative bacteria in the oral cavity producing halitosis. Chloral hydrate, phenothiazine, and paraldehyde could not be related to halitosis. The analysis showed that halitosis can be caused by medication but does not correlate to any specific disease or specific form of drug therapy. The pharmacological compounds identified as causes of halitosis are administered to treat a broad spectrum of diseases, or in therapeutic regimes.

Periodontal and biochemical bone metabolism assessment on a chronic oral anticoagulation population treated with dicoumarins.

BACKGROUND: The aim is to evaluate periodontal alteration and biochemical markers associated with bone turnover in chronic oral with dicoumarins anticoagulant treatment patients. MATERIAL AND METHODS: 80 patients treated with oral anticoagulants were divided into 2 cohort: Group A (n=36) 6 month to 1 year with anticoagulant treatment and Group B (n=44) > 2 years with anticoagulant treatment. Clinical evaluation included: Clinical attachment level (CAL), plaque index (PI) and gingival index (GI). Analytically biochemical parameters of bone remodeling (calcium and phosphorus), formation (total acid phosphatase, alkaline phosphatase and osteocalcin) and resorption (tartrate-resistant acid phosphatase and beta-crosslaps) were evaluated. RESULTS: High values of PI (67-100%) especially in men and in Group B were observed. Men with anticoagulation treatment length showed an increased GI (49.167 vs 78.083) while Group B women showed a decreased GI in comparison with Group A (59.389 vs 42.120). Women presented a greater average CAL than men as well as Group B vs Group A but without statistical significance. All biochemical markers were decreased respect to values of general population. Osteocalcin in GroupB women showed a statistically significant outcome vs GroupA (p=0.004). Acid phosphatase (total and tartrate-resistant) has a slight increase in Group B women versus Group A, and Beta-crosslap showed lower values in Group A men than Group B and slightly lower in Group A women versus Group B, without statistical significance. CONCLUSIONS: Patients showed a slight to moderate degree of periodontal affectation, especially gingivitis related to bacterial plaque. Periodontal disorders tended to be more severe in Group B. While bone remodeling showed an overall decrease with greater affectation of bone neoformation phenomena, bone destruction tended to recover and normalize in time.

Bisphosphonate-associated osteonecrosis of the jaw 2 years after teeth extractions: a case report solved with non-invasive treatment.

Bisphosphonates are a type of drugs known to inhibit bone resorption through complex interventions. Their primary mechanism of action is aimed at the cellular level, inhibiting osteoclast activity and, thus, bone resorption. Bisphosphonates are, therefore, very widely used, with many patients receiving continuous treatment for years. But it is well known that these drugs can produce osteonecrosis of the jaw and this is their principal risk. A 75-year-old woman received dental treatment before starting intravenous BP therapy for a breast cancer. She started intravenous bisphosphonate treatment with monthly protocol and after two years the patient presented a wound compatible with osteonecrosis of the jaw.

Psychometric validation of the Spanish version of the Dundee Ready Education Environment Measure applied to dental students.

AIM: To carry out a psychometric evaluation of the Spanish-language version of the Dundee Ready Education Environment Measure (DREEM) applied to dental students. METHODS: A total of 1,391 students from nine Spanish public schools of dentistry responded to the DREEM questionnaire. To analyse the reliability of the DREEM questionnaire, the internal consistency was assessed and a 'test-retest' carried out. Validity was evaluated through analysis of item response rate, floor and ceiling effects, corrected item-total and item-subscale correlations and factor structure. A confirmatory factor analysis was performed to analyse the structure of the original DREEM scale. RESULTS: Cronbach's alpha coefficient for the 'Educational Climate' (EC) global scale was 0.92. In the subscales, the 'observed' Cronbach's alpha coefficients ranged between 0.57 and 0.79 and were higher than the 'expected' ones; except for the Social subscale. In the DREEM questionnaire, all of the corrected correlation coefficients between the items and the EC global scale, and the items and their corresponding subscales, were >0.2; except for items 50 and 17. All goodness-of-fit indices of confirmatory factor analysis showed acceptable values (close to one or zero, depending on the case), and there was consistency in the results. CONCLUSIONS: The Spanish-language version of the DREEM questionnaire is a reliable and valid instrument for analysing the EC for dental students and its factor structure is supported by the data. Although our findings indicate that the DREEM may be as culturally independent as was originally stated, more research should be directed at verifying the factor structure in various languages and cultural environments.

Analysis of the 'Educational Climate' in Spanish Public Schools of Dentistry using the Dundee Ready Education Environment Measure: a multicenter study.

AIM: To analyse the 'Educational Climate' (EC) of dental students in Spain. METHODS: The study group consisted of 1391 students from nine Spanish Public Schools of Dentistry, who responded to the questionnaire based on 'Dundee Ready Education Environment Measure' (DREEM). This questionnaire has 50 items that are grouped into five domains: Learning, Teachers, Academic, Atmosphere and Social. RESULTS: The global score on the EC was 123.1 (interpretation: 'EC more positive than negative'). The scores obtained in the different domains were: 28.0 in Learning (interpretation: 'a generally positive perception of learning'), 26.8 in Teachers (interpretation: 'teachers are going in the right direction'), 20.8 in Academic (interpretation: 'feeling more on the positive side'), 29.7 in Atmosphere (interpretation: 'a generally positive atmosphere') and 17.7 in Social (interpretation: 'social perception acceptable'). In seven items (14%), an average of <2 was detected, showing that there are some educational problem areas. Regarding the EC in the different Schools of Dentistry, an average of >100 was achieved in all of them, although there were two centres that showed significantly higher values of EC. CONCLUSIONS: Spanish dental students felt that their EC was more positive than negative and considered that the different domains were positive and acceptable. However, they pointed out the existence of several educational problem areas associated with the development of a traditional curriculum. Accordingly, and in parallel with the implementation of an innovative curriculum in all Spanish Dental Schools in the coming years, immediate educational goals must address the problem areas identified, thereby further promoting a more positive perception of EC.

Femtosecond laser microstructuring of zirconia dental implants.

This study evaluated the suitability of femtosecond laser for microtexturizing cylindrical zirconia dental implants surface. Sixty-six cylindrical zirconia implants were used and divided into three groups: Control group (with no laser modification), Group A (microgropored texture), and Group B (microgrooved texture). Scanning electron microscopy observation of microgeometries revealed minimal collateral damage of the original surface surrounding the treated areas. Optical interferometric profilometry showed that ultrafast laser ablation increased surface roughness (R(a), R(q), R(z), and R(t)) significantly for both textured patterns from 1.2 x to 6 x-fold when compared with the control group (p < 0.005). With regard to chemical composition, microanalysis revealed a significant decrease of the relative content of contaminants like carbon (Control 19.7% ± 0.8% > Group B 8.4% ± 0.42% > Group A 1.6% ± 0.35%) and aluminum (Control 4.3% ± 0.9% > Group B 2.3% ± 0.3% > Group A 1.16% ± 0.2%) in the laser-treated surfaces (p < 0.005). X-ray diffraction and Raman spectra analysis were carried out to investigate any change in the crystalline structure induced by laser processing. The original predominant tetragonal phase of zirconia was preserved, whereas the traces of monoclinic phase present in the treated surfaces were reduced (Control 4.32% > Group A 1.94% > Group B 1.72%) as the surfaces were processed with ultrashort laser pulses. We concluded that femtosecond laser microstructuring offers an interesting alternative to conventional surface treatments of zirconia implants as a result of its precision and minimal damage of the surrounding areas.

Melatonin in diseases of the oral cavity.

BACKGROUND: Melatonin is the principal secretory product of the pineal gland. It has immunomodulatory and antioxidant activities, stimulates the proliferation of collagen and osseous tissue and acts as a protector against cellular degeneration associated with aging and toxin exposure. Arising out of its antioxidant actions, melatonin protects against inflammatory processes and cellular damage caused by the toxic derivates of oxygen. As a result of these actions, melatonin may be useful as a co-adjuvant in the treatment of certain conditions of the oral cavity. METHODS: An extensive review of the scientific literature was carried out using PubMed, Science Direct, ISI Web of Knowledge and the Cochrane base. RESULTS: Melatonin, which is released into the saliva, may have important implications for oral diseases. Melatonin may have beneficial effects in certain oral pathologies including periodontal diseases, herpes viral infections and Candida, local inflammatory rocesses, xerostomia, oral ulcers and oral cancer. CONCLUSIONS: Melatonin may play a role in protecting the oral cavity from tissue damage caused by oxidative stress. The experimental evidence suggests that melatonin may have utility in the treatment of several common diseases of the oral cavity. However, more specific studies are necessary to extend the therapeutic possibilities to other oral diseases.

Melatonin expression in periodontal disease.

BACKGROUND AND OBJECTIVE: It was the purpose of this study to examine the relationship between periodontal diseases and melatonin level. MATERIAL AND METHODS: Forty-six patients with periodontal disease, together with 26 age- and gender-matched healthy controls, were included. Periodontal status was assessed using the Community Periodontal Index. Plasma and salivary melatonin levels were determined using specific commercial radioimmunoassays, whereas lymphocyte subpopulations (e.g. CD3, CD4, CD8, C19 and natural killer cells) were analyzed using flow cytometry. RESULTS: Patients with periodontal disease had significantly (p < 0.001) lower plasma (9.46 +/- 3.18 pg/mL) and saliva (2.55 +/- 0.99 pg/mL) melatonin levels than healthy control patients (14.33 +/- 4.05 and 4.22 +/- 0.87 pg/mL, respectively). A biphasic relationship was observed between plasma melatonin levels and Community Periodontal Indices. The plasma melatonin level was reduced in patients with a lower Community Periodontal Index value (1 or 2) and increased in patients with a higher Community Periodontal Index value (3 or 4). Salivary melatonin parallels the changes of plasma melatonin. The higher the Community Periodontal Index, the older the patient and the higher the total lymphocyte counts. CD4 concentrations also increased as the disease worsened. CONCLUSION: The results obtained from this study suggest that melatonin could act as a protective function in fighting periodontal infection. However, further studies in this area are encouraged.

Superficies bioactivas en implantología: una nueva perspectiva / Bioactive surfaces in implantology: a new perspective

Actualmente, tras años de investigación en implantología, en los cuales se han realizado muchos trabajos, en donde se han estudiado diferentes tipos de superficies de implantes, lisas y rugosas, en un intento de mejorar, tanto en el tiempo como en la calidad , la osteointegración, se ha concluido que los implantes de superficie rugosa con un intervalo de rugosidad entre 1,0-2,0 nm, son los que parecen dar una mejor respuesta ósea y mejores resultados clínicos, pero desde un punto de vista exclusivamente mecánico. Hoy en día las investigaciones se centran en el desarrollo de superficies denominadas bioactivas, las cuales son capaces de interaccionar con el hueso que rodea al implante, como ocurre cuando el implante es revestido con carbonato cálcico o bien con flúor. Pero sabemos que dentro del metabolismo óseo, juegan importantes papeles, moléculas, como son la melatonina y la hormona del crecimiento entre otras, las cuales deben de ser tenidas en cuenta a la hora de hablar de osteointegración. Se realiza una breve descripción de la fisiología de ambas moléculas y se valora su aplicación al concepto de superficie bioactiva en implantología (AU)

At present, after years of investigation in implantology, in which there have been realized a lot of works, with different types of surfaces of implants, smooth and rough, in an attempt of improving, both in the time and in the quality, the osteointegration, one has concluded that the implants of rough surface with an interval of rugosity between 1.0-2.0 nm, are those who seem to give a better bone response and better clinical results, but from an exclusively mechanical point of view. Nowadays the investigations centre on the development of named bioactive surfaces, which are capable to react with the bone around the implant, since it happens when the implant is redressed in carbonate cálcico or in fluorine. But we know that inside the bone metabolism, there are another important molecules: the melatonin and the hormone of the growth between others, which must be born in mind at the time of speaking of osteointegration. There is realized a brief description of the physiology of both molecules and his application is valued to the concept of bioactive surface in implantology (AU)