The use of low level laser therapy in the treatment of temporomandibular joint disorders: review of the literature

Introduction: The temporomandibular disorders (TMDs) have been identified as the most important cause of pain in the facial region. The low level laser therapy (LLLT) has demonstrated to have an analgesic, anti-inflammatory and biostimulating effects. The LLLT is a noninvasive, quick and safe, non-pharmaceutical intervention that may be beneficial for patients with TMDs. However the clinical efficiency of LLLT in the treatment of this kind of disorders is controversial. Objectives: Literature review in reference to the use of LLLT in the treatment of TMDs, considering the scientific evidence level of the published studies. Material and Methods: A MEDLINE and COCHRANE database search was made for articles. The keywords used were "temporomandibular disorders" and "low level laser therapy" or "phototherapy" and by means of the Boolean operator "AND". The search provided a bank of 35 articles, and 16 relevant articles were selected to this review. These articles were critically analyzed and classified according to their level of scientific evidence. This analysis produced 3 literature review articles and 13 are clinical trials. The SORT criteria (Strength of Recommendation Taxonomy) was used to classify the articles. Results: Only one article presented an evidence level 1, twelve presented an evidence level 2, and three presented an evidence level 3. According to the principle of evidence-based dentistry, currently there is a scientific evidence level B in favor of using LLLT for treatment of TMDs. Discussion and conclusions: Publications on the use of LLLT for treatment of TMDs are limited making difficult to compare the different studies due to the great variability of the studied variables and the selected laser parameters. The great majority of the studies concluded that the results should be taken with caution due to the methodological limitations

The use of low level laser therapy in the treatment of temporomandibular joint disorders. Review of the literature

Introduction: The temporomandibular disorders (TMDs) have been identified as the most important cause of pain in the facial region. The low level laser therapy (LLLT) has demonstrated to have an analgesic, anti-inflammatory and biostimulating effects. The LLLT is a noninvasive, quick and safe, non-pharmaceutical intervention that may be beneficial for patients with TMDs. However the clinical efficiency of LLLT in the treatment of this kind of disorders is controversial. Objectives: Literature review in reference to the use of LLLT in the treatment of TMDs, considering the scientific evidence level of the published studies. Material and methods: A MEDLINE and COCHRANE database search was made for articles. The keywords used were 'temporomandibular disorders' and 'low level laser therapy' or 'phototherapy' and by means of the Boolean operator 'AND'. The search provided a bank of 35 articles, and 16 relevant articles were selected to this review. These articles were critically analyzed and classified according to their level of scientific evidence. This analysis produced 3 literature review articles and 13 are clinical trials. The SORT criteria (Strength of Recommendation Taxonomy) was used to classify the articles. Results: Only one article presented an evidence level 1, twelve presented an evidence level 2, and three presented an evidence level 3. According to the principle of evidence-based dentistry, currently there is a scientific evidence level B in favor of using LLLT for treatment of TMDs. Discussion and conclusions: Publications on the use of LLLT for treatment of TMDs are limited making difficult to compare the different studies due to the great variability of the studied variables and the selected laser parameters. The great majority of the studies concluded that the results should be taken with caution due to the methodological limitations

Crtc1 activates a transcriptional program deregulated at early Alzheimer's disease-related stages

Cognitive decline is associated with gene expression changes in the brain, but the transcriptional mechanisms underlying memory impairments in cognitive disorders, such as Alzheimer's disease (AD), are largely unknown. Here, we aimed to elucidate relevant mechanisms responsible for transcriptional changes underlying early memory loss in AD by examining pathological, behavioral, and transcriptomic changes in control and mutant β-amyloid precursor protein(APPSw,Ind) transgenic mice during aging. Genome-wide transcriptome analysis using mouse microarrays revealed deregulation of a gene network related with neurotransmission, synaptic plasticity, and learning/memory in the hippocampus of APPSw,Ind mice after spatial memory training. Specifically, APPSw,Ind mice show changes on a cAMP-responsive element binding protein(CREB)- regulated transcriptional program dependent on the CREB-regulated transcription coactivator-1 (Crtc1). Interestingly, synaptic activity and spatial memory induces Crtc1 dephosphorylation (Ser151), nuclear translocation, and Crtc1-dependent transcription in the hippocampus, and these events are impaired in APPSw,Ind mice at early pathological and cognitive decline stages. CRTC1-dependent genes and CRTC1 levels are reduced in human hippocampus at intermediate Braak III/IV pathological stages. Importantly, adeno-associated viral-mediated Crtc1 overexpression in the hippocampus efficiently reverses Aβ-induced spatial learning and memory deficits by restoring a specific subset of Crtc1 target genes. Our results reveal a critical role of Crtc1-dependent transcription on spatial memory formation and provide the first evidence that targeting brain transcriptome reverses memory loss in AD

Short-Term Environmental Enrichment Rescues Adult Neurogenesis and Memory Deficits in APPSw,Ind Transgenic Mice

Epidemiological studies indicate that intellectual activity prevents or delays the onset of Alzheimer's disease (AD). Similarly, cognitive stimulation using environmental enrichment (EE), which increases adult neurogenesis and functional integration of newborn neurons into neural circuits of the hippocampus, protects against memory decline in transgenic mouse models of AD, but the mechanisms involved are poorly understood. To study the therapeutic benefits of cognitive stimulation in AD we examined the effects of EE in hippocampal neurogenesis and memory in a transgenic mouse model of AD expressing the human mutant β-amyloid (Aβ) precursor protein (APPSw,Ind). By using molecular markers of new generated neurons (bromodeoxiuridine, NeuN and doublecortin), we found reduced neurogenesis and decreased dendritic length and projections of doublecortin-expressing cells of the dentate gyrus in young APPSw,Ind transgenic mice. Moreover, we detected a lower number of mature neurons (NeuN positive) in the granular cell layer and a reduced volume of the dentate gyrus that could be due to a sustained decrease in the incorporation of new generated neurons. We found that short-term EE for 7 weeks efficiently ameliorates early hippocampal-dependent spatial learning and memory deficits in APPSw,Ind transgenic mice. The cognitive benefits of enrichment in APPSw,Ind transgenic mice were associated with increased number, dendritic length and projections to the CA3 region of the most mature adult newborn neurons. By contrast, Aβ levels and the total number of neurons in the dentate gyrus were unchanged by EE in APPSw,Ind mice. These results suggest that promoting the survival and maturation of adult generated newborn neurons in the hippocampus may contribute to cognitive benefits in AD mouse models

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

La evaluación de las políticas municipales de juventud a partir de un sistema de indicadores

(analítico):En este artículo presentamos un sistema de indicadores (SIAPJove) para evaluar políticas municipales de juventud. El sistema ha sido creado y validado por un grupo de individuos expertos y se ha aplicado en tres municipios de Cataluña en el Estado Español, en forma de estudio de caso para comprobar su aplicabilidad y eficacia. El resultado es un instrumento con 12 ámbitos de evaluación, 32 objetivos de evaluación y 83 indicadores. Permite evaluar la situación de dichas políticas, hacer evidentes las tendencias y los cambios, valorar su nivel de eficacia y contribuir a establecer objetivos a corto y medio plazo. Asimismo, se puede utilizar como herramienta para la autoevaluación, para reflexionar sobre la propia acción y aprender de los errores y las dificultades en el desarrollo de las políticas municipales de juventud

The use of low level laser therapy in the treatment of temporomandibular joint disorders. Review of the literature

Introduction: The temporomandibular disorders (TMDs) have been identified as the most important cause of pain in the facial region. The low level laser therapy (LLLT) has demonstrated to have an analgesic, anti-inflammatory and biostimulating effects. The LLLT is a noninvasive, quick and safe, non-pharmaceutical intervention that may be beneficial for patients with TMDs. However the clinical efficiency of LLLT in the treatment of this kind of disorders is controversial. Objectives: Literature review in reference to the use of LLLT in the treatment of TMDs, considering the scientific evidence level of the published studies. Material and methods: A MEDLINE and COCHRANE database search was made for articles. The keywords used were 'temporomandibular disorders' and 'low level laser therapy' or 'phototherapy' and by means of the Boolean operator 'AND'. The search provided a bank of 35 articles, and 16 relevant articles were selected to this review. These articles were critically analyzed and classified according to their level of scientific evidence. This analysis produced 3 literature review articles and 13 are clinical trials. The SORT criteria (Strength of Recommendation Taxonomy) was used to classify the articles. Results: Only one article presented an evidence level 1, twelve presented an evidence level 2, and three presented an evidence level 3. According to the principle of evidence-based dentistry, currently there is a scientific evidence level B in favor of using LLLT for treatment of TMDs. Discussion and conclusions: Publications on the use of LLLT for treatment of TMDs are limited making difficult to compare the different studies due to the great variability of the studied variables and the selected laser parameters. The great majority of the studies concluded that the results should be taken with caution due to the methodological limitations

Soluble oligomers of amyloid-beta peptide disrupt membrane trafficking of alpha-amino-3-hydroxy-5-methylisoxazole-4 propionic acid receptor (AMPAR) contributing to early synapse dysfunction

β-Amyloid (Aβ), a peptide generated from the amyloid precursor protein, is widely believed to underlie the pathophysiology of Alzheimer disease (AD). Emerging evidences suggest that soluble Aβ oligomers adversely affect synaptic function, leading to cognitive failure associated with AD. The Aβ-induced synaptic dysfunction has been attributed to the synaptic removal of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors (AMPARs). However, the molecular mechanisms underlying the loss of AMPAR induced by Aβ at synapses are largely unknown. In this study we have examined the effect of Aβ oligomers on phosphorylated GluA1 at serine 845, a residue that plays an essential role in the trafficking of AMPARs toward extrasynaptic sites and the subsequent delivery to synapses during synaptic plasticity events. We found that Aβ oligomers reduce basal levels of Ser-845 phosphorylation and surface expression of AMPARs affecting AMPAR subunit composition. Aβ-induced GluA1 dephosphorylation and reduced receptor surface levels are mediated by an increase in calcium influx into neurons through ionotropic glutamate receptors and activation of the calcium-dependent phosphatase calcineurin. Moreover, Aβ oligomers block the extrasynaptic delivery of AMPARs induced by chemical synaptic potentiation. In addition, reduced levels of total and phosphorylated GluA1 are associated with initial spatial memory deficits in a transgenic mouse model of AD. These findings indicate that Aβ oligomers could act as a synaptic depressor affecting the mechanisms involved in the targeting of AMPARs to the synapses during early stages of the disease