Biostimulation with low-level laser therapy and its effects on soft and hard tissue regeneration. Literature review

Objective. Low-Level Laser Therapy encourages the healing process, reduces inflammation and pain. The aim of this study is to identify the impact of Low-Level Laser Therapy on tissue regeneration with special attention to hard tissues and to compare the effect of several wave lengths in the proliferation and differentiation of cells. Methods. The keywords used were “bone regeneration”, “laser therapy”, “photobiomodulation” OR “bio-stimulation”, “Low-Level Laser therapy” OR “LLLT”, “osteoblast proliferation” AND “differentiation”. Results. The bio-stimulation with Low-Level Laser Therapy also seems to interfere with the osseous integration of implants, by increasing its adherence on the bone-implant surfaces. Evidence has shown that Low-Level Laser Therapy influences the cellular proliferation and differentiation. Conclusions. Low-Level Laser Therapy is a promising therapy in the field of regeneration, but further studies are needed in order to define the standard protocol

The genetic history of the Southern Arc: a bridge between West Asia and Europe

By sequencing 727 ancient individuals from the Southern Arc (Anatolia and its neighbors in Southeastern Europe and West Asia) over 10,000 years, we contextualize its Chalcolithic period and Bronze Age (about 5000 to 1000 BCE), when extensive gene flow entangled it with the Eurasian steppe. Two streams of migration transmitted Caucasus and Anatolian/Levantine ancestry northward, and the Yamnaya pastoralists, formed on the steppe, then spread southward into the Balkans and across the Caucasus into Armenia, where they left numerous patrilineal descendants. Anatolia was transformed by intra–West Asian gene flow, with negligible impact of the later Yamnaya migrations. This contrasts with all other regions where Indo-European languages were spoken, suggesting that the homeland of the Indo-Anatolian language family was in West Asia, with only secondary dispersals of non-Anatolian Indo-Europeans from the steppe

Analysis of protein dynamics at active, stalled, and collapsed replication forks

Successful DNA replication and packaging of newly synthesized DNA into chromatin are essential to maintain genome integrity. Defects in the DNA template challenge genetic and epigenetic inheritance. Unfortunately, tracking DNA damage responses (DDRs), histone deposition, and chromatin maturation at replication forks is difficult in mammalian cells. Here we describe a technology called iPOND (isolation of proteins on nascent DNA) to analyze proteins at active and damaged replication forks at high resolution. Using this methodology, we define the timing of histone deposition and chromatin maturation. Class 1 histone deacetylases are enriched at replisomes and remove predeposition marks on histone H4. Chromatin maturation continues even when decoupled from replisome movement. Furthermore, fork stalling causes changes in the recruitment and phosphorylation of proteins at the damaged fork. Checkpoint kinases catalyze H2AX phosphorylation, which spreads from the stalled fork to include a large chromatin domain even prior to fork collapse and double-strand break formation. Finally, we demonstrate a switch in the DDR at persistently stalled forks that includes MRE11-dependent RAD51 assembly. These data reveal a dynamic recruitment of proteins and post-translational modifications at damaged forks and surrounding chromatin. Furthermore, our studies establish iPOND as a useful methodology to study DNA replication and chromatin maturation

Effects of non-surgical periodontal therapy on periodontal laboratory and clinical data as well as on disease activity in patients with rheumatoid arthritis.

OBJECTIVES To compare the effect of non-surgical periodontal therapy on clinical and inflammatory parameters in patients with moderate to severe chronic periodontitis (CP) and rheumatoid arthritis (RA) (RA-CP) with that in CP patients without RA. MATERIAL AND METHODS Eighteen patients with RA-CP and 18 systemically healthy patients with CP were treated with scaling and root planing (SRP) within 24 h. At baseline, and at 3 and 6 months after SRP, clinical periodontal parameters, inflammatory markers, and microorganisms in subgingival biofilm were assessed. In addition, disease activity markers of RA (DAS28, CRP, ESR) and specific antibodies (RF) were monitored in the RA-CP group. RESULTS In both groups, non-surgical therapy yielded to statistically significant improvements in all investigated clinical periodontal variables; in RA patients, a statistically significant decrease in serum-CRP was seen at 3 months. At all time-points, levels of inflammatory markers in GCF were higher in RA-CP than in CP patients. Counts of Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola decreased statistically significantly in CP but not in the RA-CP group. Changes of DAS28 correlated positively with those of P. gingivalis and negatively with the plaque index. CONCLUSIONS Within their limits, the present data suggest that (a) non-surgical periodontal therapy improves periodontal conditions in CP patients with and without RA and (b) in patients with RA, eradication of P. gingivalis in conjunction with a high level oral hygiene may transiently decrease disease activity of RA. CLINICAL RELEVANCE In patients with RA and CP, non-surgical periodontal therapy is a relevant modality not only to improve the periodontal condition but also to decrease RA activity

Links between Metabolic Syndrome and Hypertension: The Relationship with the Current Antidiabetic Drugs

Hypertension poses a significant burden in the general population, being responsible for increasing cardiovascular morbidity and mortality, leading to adverse outcomes. Moreover, the association of hypertension with dyslipidaemia, obesity, and insulin resistance, also known as metabolic syndrome, further increases the overall cardiovascular risk of an individual. The complex pathophysiological overlap between the components of the metabolic syndrome may in part explain how novel antidiabetic drugs express pleiotropic effects. Taking into consideration that a significant proportion of patients do not achieve target blood pressure values or glucose levels, more efforts need to be undertaken to increase awareness among patients and physicians. Novel drugs, such as incretin-based therapies and renal glucose reuptake inhibitors, show promising results in decreasing cardiovascular events in patients with metabolic syndrome. The effects of sodium-glucose co-transporter-2 inhibitors are expressed at different levels, including renoprotection through glucosuria, natriuresis and decreased intraglomerular pressure, metabolic effects such as enhanced insulin sensitivity, cardiac protection through decreased myocardial oxidative stress and, to a lesser extent, decreased blood pressure values. These pleiotropic effects are also observed after treatment with glucagon-like peptide-1 receptor agonists, positively influencing the cardiovascular outcomes of patients with metabolic syndrome. The initial combination of the two classes may be the best choice in patients with type 2 diabetes mellitus and multiple cardiovascular risk factors because of their complementary mechanisms of action. In addition, the novel mineralocorticoid receptor antagonists show significant cardio-renal benefits, as well as anti-inflammatory and anti-fibrotic effects. Overall, the key to better control of hypertension in patients with metabolic syndrome is to consider targeting multiple pathogenic mechanisms, using a combination of the different therapeutic agents, as well as drastic lifestyle changes. This article will briefly summarize the association of hypertension with metabolic syndrome, as well as take into account the influence of antidiabetic drugs on blood pressure control

ATR-p53 restricts homologous recombination in response to replicative stress but does not limit DNA interstrand crosslink repair in lung cancer cells.

Homologous recombination (HR) is required for the restart of collapsed DNA replication forks and error-free repair of DNA double-strand breaks (DSB). However, unscheduled or hyperactive HR may lead to genomic instability and promote cancer development. The cellular factors that restrict HR processes in mammalian cells are only beginning to be elucidated. The tumor suppressor p53 has been implicated in the suppression of HR though it has remained unclear why p53, as the guardian of the genome, would impair an error-free repair process. Here, we show for the first time that p53 downregulates foci formation of the RAD51 recombinase in response to replicative stress in H1299 lung cancer cells in a manner that is independent of its role as a transcription factor. We find that this downregulation of HR is not only completely dependent on the binding site of p53 with replication protein A but also the ATR/ATM serine 15 phosphorylation site. Genetic analysis suggests that ATR but not ATM kinase modulates p53's function in HR. The suppression of HR by p53 can be bypassed under experimental conditions that cause DSB either directly or indirectly, in line with p53's role as a guardian of the genome. As a result, transactivation-inactive p53 does not compromise the resistance of H1299 cells to the interstrand crosslinking agent mitomycin C. Altogether, our data support a model in which p53 plays an anti-recombinogenic role in the ATR-dependent mammalian replication checkpoint but does not impair a cell's ability to use HR for the removal of DSB induced by cytotoxic agents

Native and Prosthetic Simultaneously Double Valve Infective Endocarditis with Enterococcus faecalis—Case-Based Review

Infective endocarditis is a severe infective heart disease, commonly involving native or prosthetic valves. It frequently presents with univalvular involvement and simultaneous double valve or multivalvular involvement is rarely described. The third leading cause of infective endocarditis worldwide is Enterococcus faecalis, which is associated with high mortality rates despite important advances in antimicrobial therapy. It develops secondary to enterococcal bacteremia, with its origin from the gastrointestinal or genitourinary tract and predominantly affecting the elderly population with multiple comorbidities. Clinical presentation is usually less typical, and the treatment is challenging. It can be marked by antibiotic resistance, side effects, and subsequent complications. Surgical treatment can be considered if deemed appropriate. To the best of our knowledge, we present the first case-based narrative review of Enterococcus faecalis double valve endocarditis involving both the aortic native and prosthetic mitral valve, highlighting the clinical characteristics, treatment, and complications of this condition

Recognition and Management of Serotonin Toxidrome in the Emergency Department—Case Based Review

Serotonin syndrome (SS) is a clinical toxidrome with high variability in clinical practice. It develops due to increased serotonin levels in the central nervous system. With an underestimated frequency, SS can develop following an overdose, a therapeutic dose increase, or drug to drug interaction of at least one serotonergic agent. It can present with autonomic signs, neuromuscular changes and an altered mental status. However, history and clinical examination are key features to formulate the diagnosis. Treatment options consist of supportive measures, discontinuation of the offending agent and certain therapeutic agents previously reported to improve outcomes. Physicians have limited experience with SS, partially due to the lack of its identification in clinical practice. Therefore, we have integrated, in a narrative review, the case of a young male with SS following an atypical antipsychotic overdose superimposed on chronic treatment with agents previously known to produce SS