The use of integrin binding domain loaded hydrogel (RGD) with minimally invasive surgical technique in treatment of periodontal intrabony defect: a randomized clinical and biochemical study.

BACKGROUND: Periodontal regeneration faces multiple challenges, the most important being cellular insufficiency. In an attempt to improve defect cellularity, we aimed to demonstrate enhancing cellular attraction using arginine-glycine-aspartic acid (RGD) adhesion molecule legend blended hydrogel within the intrabony defects. METHODOLOGY: Forty-five intrabony defects were selected from patients with stage III or IV - grade A or B periodontitis and divided randomly into three equal groups of 15 each: group1 (G1): received minimally invasive surgical technique (MIST) alone, group2 (G2): received MIST and placebo hydrogel injection, and group3 (G3): were treated with MIST and RGD hydrogel injection. Primary outcomes 6 months following therapy were; defect base fill (DBF) and defect width measurement (DW); secondary outcomes were clinical attachment level (CAL), pocket depth (PD), plaque index (PI), gingival index (GI), and biochemical analysis of bone morphogenetic protein (BMP-2) evaluated at 1,7,14 and 21 days following therapy. RESULTS: Significant improvements in DBF, CAL, and PD were observed in the three studied groups 6 months following therapy compared to baseline (p<0.05). A significant improvement in DBF was reported in G3 compared to G1 and 2 (p=0.005). Additionally, a significantly higher CAL gain was reported in G3 compared to that of G1 (p=0.02). Group 3 was associated with a significantly higher level of BMP-2 compared to G1 and G2 in all reported periods. CONCLUSION: RGD peptide carried on a hydrogel delivery agent and contained with a minimally invasive flap could be a reliable option in improving the outcomes of periodontal therapy.

The use of integrin binding domain loaded hydrogel (RGD) with minimally invasive surgical technique in treatment of periodontal intrabony defect: a randomized clinical and biochemical study

Abstract Periodontal regeneration faces multiple challenges, the most important being cellular insufficiency. In an attempt to improve defect cellularity, we aimed to demonstrate enhancing cellular attraction using arginine-glycine-aspartic acid (RGD) adhesion molecule legend blended hydrogel within the intrabony defects. Methodology Forty-five intrabony defects were selected from patients with stage III or IV - grade A or B periodontitis and divided randomly into three equal groups of 15 each: group1 (G1): received minimally invasive surgical technique (MIST) alone, group2 (G2): received MIST and placebo hydrogel injection, and group3 (G3): were treated with MIST and RGD hydrogel injection. Primary outcomes 6 months following therapy were; defect base fill (DBF) and defect width measurement (DW); secondary outcomes were clinical attachment level (CAL), pocket depth (PD), plaque index (PI), gingival index (GI), and biochemical analysis of bone morphogenetic protein (BMP-2) evaluated at 1,7,14 and 21 days following therapy. Results Significant improvements in DBF, CAL, and PD were observed in the three studied groups 6 months following therapy compared to baseline (p<0.05). A significant improvement in DBF was reported in G3 compared to G1 and 2 (p=0.005). Additionally, a significantly higher CAL gain was reported in G3 compared to that of G1 (p=0.02). Group 3 was associated with a significantly higher level of BMP-2 compared to G1 and G2 in all reported periods. Conclusion RGD peptide carried on a hydrogel delivery agent and contained with a minimally invasive flap could be a reliable option in improving the outcomes of periodontal therapy.

Shear bond strength of composite repair system to bilayered zirconia using different surface treatments (in vitro study) / Resistência ao cisalhamento de reparos de resina composta e zircônia bicamada usando diferentes tratamentos de superfície (estudo in vitro)

Objective: the study is aimed to evaluate the effect of different surface treatment methods on shear bond strength between composite repair system and both of zirconia core and veneering porcelain and analyze the mode of failure between composite repair and ceramic surface. Material and methods: 40 Ceramic discs were fabricated with diameter of 7mm and 3mm thickness and divided according to material into two groups, Zirconia core discs (n = 20) and veneering porcelain discs (n = 20). Specimens were thermocycled and then each group was subdivided according to surface treatment method into 4 equal sub groups (n = 5) ,control subgroup I air abrasion, subgroup II Cojet, subgroup III laser, subgroup IV combination of air abrasion and laser surface treatment. Composite blocks were built up and polymerized on the surface of the specimens and shear bond strength of composite to each specimen was tested using a universal testing machine and mode of failure was evaluated using stereomicroscope. Results: Regardless of ceramic type; there was a statistically significant difference between surface treatments. Cojet recorded the highest mean shear bond strength. Laser showed the highest prevalence of adhesive failure. Porcelain + Cojet showed the highest prevalence of cohesive failure. Conclusion: Cojet surface treatment provided superior shear bond strength regardless of the ceramic type whether zirconia or porcelain. Porcelain provided superior shear bond strength values in comparison to zirconia regardless of the surface treatment method tested. Porcelain showed higher percentage of cohesive failure that while the mode of failure in zirconia was most commonly adhesive. (AU)

Objetivo: O objetivo deste estudo foi avaliar o efeito de diferentes métodos de tratamento de superfície na resistência ao cisalhamento de reparos de resina composta e núcleos de zircônia ou cobertura de porcelana, e analisar o modo de falha entre o reparo e a superfície cerâmica. Material e métodos: 40 discos de cerâmica foram fabricados com diâmetro de 7 mm e 3 mm de espessura e divididos de acordo com o material em dois grupos, discos de zircônia (n = 20) e discos de porcelana (n = 20). As amostras foram termocicladas e, em seguida, cada grupo foi subdividido de acordo com o método de tratamento de superfície em 4 subgrupos iguais (n = 5), subgrupo I :controle (abrasão a ar); subgrupo II: Cojet; subgrupo III: laser; subgrupo IV: combinação de abrasão a ar e tratamento de superfície a laser. Blocos de resina composta foram construídos e polimerizados na superfície das amostras e a resistência ao cisalhamento do compósito para cada amostra foi testada usando uma máquina de teste universal e o modo de falha foi avaliado usando o estereomicroscópio. Resultados: Independentemente do tipo de cerâmica houve diferença estatisticamente significante entre os tratamentos de superfície. Cojet registrou a maior força média de união ao cisalhamento. O laser mostrou a maior prevalência de falha adesiva. Porcelana + Cojet apresentou a maior prevalência de falha coesiva. Conclusão: O tratamento superficial com Cojet proporcionou resistência superior ao cisalhamento, independentemente do tipo de cerâmica, seja zircônia ou porcelana. A porcelana forneceu valores superiores de resistência ao cisalhamento em comparação com a zircônia, independentemente do método de tratamento de superfície testado. A porcelana apresentou maior porcentagem de falha coesiva que enquanto o modo de falha na zircônia era mais comumente adesivo. (AU)

Re-thinking the Etiological Framework of Neurodegeneration.

Neurodegenerative diseases are among the leading causes of disability and death worldwide. The disease-related socioeconomic burden is expected to increase with the steadily increasing life expectancy. In spite of decades of clinical and basic research, most strategies designed to manage degenerative brain diseases are palliative. This is not surprising as neurodegeneration progresses "silently" for decades before symptoms are noticed. Importantly, conceptual models with heuristic value used to study neurodegeneration have been constructed retrospectively, based on signs and symptoms already present in affected patients; a circumstance that may confound causes and consequences. Hence, innovative, paradigm-shifting views of the etiology of these diseases are necessary to enable their timely prevention and treatment. Here, we outline four alternative views, not mutually exclusive, on different etiological paths toward neurodegeneration. First, we propose neurodegeneration as being a secondary outcome of a primary cardiovascular cause with vascular pathology disrupting the vital homeostatic interactions between the vasculature and the brain, resulting in cognitive impairment, dementia, and cerebrovascular events such as stroke. Second, we suggest that the persistence of senescent cells in neuronal circuits may favor, together with systemic metabolic diseases, neurodegeneration to occur. Third, we argue that neurodegeneration may start in response to altered body and brain trophic interactions established via the hardwire that connects peripheral targets with central neuronal structures or by means of extracellular vesicle (EV)-mediated communication. Lastly, we elaborate on how lifespan body dysbiosis may be linked to the origin of neurodegeneration. We highlight the existence of bacterial products that modulate the gut-brain axis causing neuroinflammation and neuronal dysfunction. As a concluding section, we end by recommending research avenues to investigate these etiological paths in the future. We think that this requires an integrated, interdisciplinary conceptual research approach based on the investigation of the multimodal aspects of physiology and pathophysiology. It involves utilizing proper conceptual models, experimental animal units, and identifying currently unused opportunities derived from human data. Overall, the proposed etiological paths and experimental recommendations will be important guidelines for future cross-discipline research to overcome the translational roadblock and to develop causative treatments for neurodegenerative diseases.

Pertuzumab and trastuzumab: the rationale way to synergy.

It has now been 15 years since the HER2-targeted monoclonal antibody trastuzumab was introduced in clinical and revolutionized the treatment of HER2-positive breast cancer patients. Despite this achievement, most patients with HER2-positive metastatic breast cancer still show progression of their disease, highlighting the need for new therapies. The continuous interest in novel targeted agents led to the development of pertuzumab, the first in a new class of agents, the HER dimerization inhibitors. Pertuzumab is a novel recombinant humanized antibody directed against extracellular domain II of HER2 protein that is required for the heterodimerization of HER2 with other HER receptors, leading to the activation of downstream signalling pathways. Pertuzumab combined with trastuzumab plus docetaxel was approved for the first-line treatment of patients with HER2-positive metastatic breast cancer and is currently used as a standard of care in this indication. In the neoadjuvant setting, the drug was granted FDA-accelerated approval in 2013. Pertuzumab is also being evaluated in the adjuvant setting. The potential of pertuzumab relies in the dual complete blockade of the HER2/3 axis when administered with trastuzumab. This paper synthetises preclinical and clinical data on pertuzumab and highlights the mechanisms underlying the synergistic activity of the combination pertuzumab-trastuzumab which are essentially due to their complementary mode of action.