Unveiling DNA methylation in Alzheimer’s disease:a review of array-based human brain studies

The intricacies of Alzheimer’s disease pathogenesis are being increasingly illuminated by the exploration of epigenetic mechanisms,particularly DNA methylation.This review comprehensively surveys recent human-centered studies that investigate whole genome DNA methylation in Alzheimer’s disease neuropathology.The examination of various brain regions reveals distinctive DNA methylation patterns that associate with the Braak stage and Alzheimer’s disease progression.The entorhinal cortex emerges as a focal point due to its early histological alterations and subsequent impact on downstream regions like the hippocampus.Notably,ANK1 hypermethylation,a protein implicated in neurofibrillary tangle formation,was recurrently identified in the entorhinal cortex.Further,the middle temporal gyrus and prefrontal cortex were shown to exhibit significant hypermethylation of genes like HOXA3,RHBDF2,and MCF2L,potentially influencing neuroinflammatory processes.The complex role of BIN1 in late-onset Alzheimer’s disease is underscored by its association with altered methylation patterns.Despite the disparities across studies,these findings highlight the intricate interplay between epigenetic modifications and Alzheimer’s disease pathology.Future research efforts should address methodological variations,incorporate diverse cohorts,and consider environmental factors to unravel the nuanced epigenetic landscape underlying Alzheimer’s disease progression.

Novel insights into D-Pinitol based therapies:a link between tau hyperphosphorylation and insulin resistance

Alzheimer’s disease is a neurodegenerative disorder characterized by the amyloid accumulation in the brains of patients with Alzheimer’s disease.The pathogenesis of Alzheimer’s disease is mainly mediated by the phosphorylation and aggregation of tau protein.Among the multiple causes of tau hyperphosphorylation,brain insulin resistance has generated much attention,and inositols as insulin sensitizers,are currently considered candidates for drug development.The present narrative review revises the interactions between these three elements:Alzheimer’s disease-tau-inositols,which can eventually identify targets for new disease modifiers capable of bringing hope to the millions of people affected by this devastating disease.

A comprehensive look at the psychoneuroimmunoendocrinology of spinal cord injury and its progression: mechanisms and clinical opportunities

Spinal cord injury(SCI)is a devastating and disabling medical condition generally caused by a traumatic event(primary injury).This initial trauma is accompanied by a set of biological mechanisms directed to ameliorate neural damage but also exacerbate initial damage(secondary injury).The alterations that occur in the spinal cord have not only local but also systemic consequences and virtually all organs and tissues of the body incur important changes after SCI,explaining the progression and detrimental consequences related to this condition.Psychoneuroimmunoendocrinology(PNIE)is a growing area of research aiming to integrate and explore the interactions among the different systems that compose the human organism,considering the mind and the body as a whole.The initial traumatic event and the consequent neurological disruption trigger immune,endocrine,and multisystem dysfunction,which in turn affect the patient's psyche and well-being.In the present review,we will explore the most important local and systemic consequences of SCI from a PNIE perspective,defining the changes occurring in each system and how all these mechanisms are interconnected.Finally,potential clinical approaches derived from this knowledge will also be collectively presented with the aim to develop integrative therapies to maximize the clinical management of these patients.

Present and future of new systemic therapies for early and intermediate stages of hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is a high mortality neoplasm which usually appears on a cirrhotic liver.The therapeutic arsenal and subsequent prognostic outlook are intrinsically linked to the HCC stage at diagnosis.Notwithstanding the current deployment of treatments with curative intent(liver resection/local ablation and liver transplantation)in early and intermediate stages,a high rate of HCC recurrence persists,underscoring a pivotal clinical challenge.Emergent systemic therapies(ST),particularly immunotherapy,have demonstrate promising outcomes in terms of increase overall survival,but they are currently bound to the advanced stage of HCC.This review provides a comprehensive analysis of the literature,encompassing studies up to March 10,2024,evaluating the impact of novel ST in the early and intermediate HCC stages,specially focusing on the findings of neoadjuvant and adjuvant regimens,aimed at increasing significantly overall survival and recurrence-free survival after a treatment with curative intent.We also investigate the potential role of ST in enhancing the downstaging rate for the intermediate-stage HCC initially deemed ineligible for treatment with curative intent.Finally,we critically discuss about the current relevance of the results of these studies and the encouraging future implications of ST in the treatment schedules of early and intermediate HCC stages.

Systemic Inflammation Response Index and weight loss as prognostic factors in metastatic pancreatic cancer: A concept study from the PANTHEIA-SEOM trial

BACKGROUND The prognostic value of the Systemic Inflammation Response Index(SIRI)in advanced pancreatic cancer is recognized,but its correlation with patients´nutritional status and outcomes remains unexplored.AIM To study the prognostic significance of SIRI and weight loss in metastatic pancreatic cancer.METHODS The PANTHEIA-Spanish Society of Medical Oncology(SEOM)study is a multicentric(16 Spanish hospitals),observational,longitudinal,non-interventional initiative,promoted by the SEOM Real World-Evidence work group.This pilot study sought to analyze the association between weight loss and inflammatory status as defined by SIRI.The cohort stems from a proof-of-concept pilot study conducted at one of the coordinating centers.Patients with pathologically confirmed metastatic pancreatic adenocarcinoma,treated from January 2020 to January 2023,were included.The index was calculated using the product of neutrophil and monocyte counts,divided by lymphocyte counts,obtained within 15 days before initiation chemotherapy.This study evaluated associations between overall survival(OS),SIRI and weight loss.RESULTS A total of 50 patients were included.66%of these patients were male and the median age was 66 years.Metastasis sites:36%liver,12%peritoneal carcinomatosis,10%lung,and 42%multiple locations.Regarding the first line palliative chemotherapy treatments:50%received gemcitabine plus nab-paclitaxel;28%,modified fluorouracil,leucovorin,irinotecan and oxaliplatin,and 16%were administered gemcitabine.42%had a weight loss>5%in the three months(mo)preceding diagnosis.21 patients with a SIRI≥2.3×10^(3)/L exhibited a trend towards a lower median OS compared to those with a SIRI<2.3×10^(3)/L(4 vs 18 mo;P<0.000).Among 21 patients with>5%weight loss before diagnosis,the median OS was 6 mo,in contrast to 19 mo for those who did not experience such weight loss(P=0.003).Patients with a weight loss>5%showed higher SIRI levels.This difference was statistically significant(P<0.000).For patients with a SIRI<2.3×10^(3)/L,those who did not lose>5%of their weight had an OS of 20 mo,compared to 11 mo for those who did(P<0.001).No association was found between carbohydrate antigen 19-9 levels≥1000 U/mL and weight loss.CONCLUSION A higher SIRI was correlated with decreased survival rates in patients with metastatic pancreatic cancer and associated with weight loss.An elevated SIRI is suggested as a predictor of survival,emphasizing the need for prospective validation in the upcoming PANTHEIA-SEOM study.

Quantitative assessment of self-management in patients with nonalcoholic fatty liver disease: An unmet clinical need

In this editorial we comment on the article titled“Establishment and validation of an adherence prediction system for lifestyle interventions in non-alcoholic fatty liver disease”by Zeng et al published in a recent issue of the World Journal of Gastroenterology.Non-alcoholic fatty liver disease(NAFLD)represents one of the current challenges in hepatology and public health,due to its continuous growing prevalence and the rising incidence of NAFLD-related fibrosis,non-alcoholic steatohepatitis and cirrhosis.The only effective therapeutic strategy for this dis-ease is represented by encouraging patients to improve their lifestyle through the modification of dietary intake and increased physical exercise,but the effective application of such modifications is often limited by various factors such as lack of information,psychological barriers or poor social support.While poor adherence to a healthy lifestyle can be decisive in determining the clinical outcome,in daily practice there is a lack of quantitative instruments aimed at identifying patients with the lowest adherence to lifestyle changes and higher risk of disease progre-ssion in the course of follow-up.In this article,Zeng et al propose a quantitative scale to assess the grade of adherence of patients with NAFLD to hea-lthy lifestyle intervention,called the Exercise and Diet Adherence Scale(EDAS).This scale,consisting of 33 items divided into 6 dimensions which relates to six subjective aspects in the self-management of NAFLD,has shown a good correlation with the identification of the sub-cohort of patients with the highest reduction in caloric intake,increase in physical exercise,probability of a reduction in liver stiffness measurement and alanine aminotransferase levels.The cor-relation among clinical outcomes and specific dimensions of this scale also highlights the pivotal role of a good and confidential doctor-patient relationship and of an effective communication.There is an urgent need for practical and effective instruments to assess the grade of self-management of NAFLD patients,together with the development of multidisciplinary teams with the aim of applying structured behavioral interventions.

Omics-based biomarkers as useful tools in metabolic dysfunctionassociated steatotic liver disease clinical practice:How far are we?

Unmet needs exist in metabolic dysfunction-associated steatotic liver disease(MASLD)risk stratification.Our ability to identify patients with MASLD with advanced fibrosis and at higher risk for adverse outcomes is still limited.Incorporating novel biomarkers could represent a meaningful improvement to current risk predictors.With this aim,omics technologies have revolutionized the process of MASLD biomarker discovery over the past decades.While the research in this field is thriving,much of the publication has been haphazard,often using single-omics data and specimen sets of convenience,with many identified candidate biomarkers but lacking clinical validation and utility.If we incorporate these biomarkers to direct patients’management,it should be considered that the roadmap for translating a newly discovered omics-based signature to an actual,analytically valid test useful in MASLD clinical practice is rigorous and,therefore,not easily accomplished.This article presents an overview of this area’s current state,the conceivable opportunities and challenges of omics-based laboratory diagnostics,and a roadmap for improving MASLD biomarker research.

Shear-wave elastography to predict hepatocellular carcinoma after hepatitis C virus eradication:A systematic review and meta-analysis

BACKGROUND Direct-acting antiviral agents(DAAs)are highly effective treatment for chronic hepatitis C(CHC)with a significant rate of sustained virologic response(SVR).The achievement of SVR is crucial to prevent additional liver damage and slow down fibrosis progression.The assessment of fibrosis degree can be performed with transient elastography,magnetic resonance elastography or shear-wave elastography(SWE).Liver elastography could function as a predictor for hepato-cellular carcinoma(HCC)in CHC patients treated with DAAs.AIM To explore the predictive value of SWE for HCC development after complete clearance of hepatitis C virus(HCV).METHODS A comprehensive literature search of clinical studies was performed to identify the ability of SWE to predict HCC occurrence after HCV clearance.In accordance with the study protocol,a qualitative and quantitative analysis of the evidence was planned.RESULTS At baseline and after 12 wk of follow-up,a trend was shown towards greater liver stiffness(LS)in those who go on to develop HCC compared to those who do not[baseline LS standardized mean difference(SMD):1.15,95%confidence interval(95%CI):020-2.50;LS SMD after 12 wk:0.83,95%CI:0.33-1.98].The absence of a statistically significant difference between the mean LS in those who developed HCC or not may be related to the inability to correct for confounding factors and the absence of raw source data.There was a statist-ically significant LS SMD at 24 wk of follow-up between patients who developed HCC vs not(0.64;95%CI:0.04-1.24).CONCLUSION SWE could be a promising tool for prediction of HCC occurrence in patients treated with DAAs.Further studies with larger cohorts and standardized timing of elastographic evaluation are needed to confirm these data.

Mixed neuroendocrine non-neuroendocrine neoplasms in gastroenteropancreatic tract

Mixed neuroendocrine non-neuroendocrine neoplasms(MiNENs)are a hetero-geneous group of malignant neoplasms that can settle in the gastroenteropan-creatic tract.They are composed of a neuroendocrine(NE)and a non-NE compo-nent in at least 30%of each tumour.The non-NE component can include different histological combinations of glandular,squamous,mucinous and sarcomatoid phenotypes,and one or both of the components can be low-or high grade malignant.Recent changes in the nomenclature of these neoplasms might lead to great deal of confusion,and the lack of specific clinical trials is the main reason why their management is difficult.The review aims to clarify the definition of MiNEN and analyze available evidence about their diagnosis and treatment options according to their location and extension through careful analysis of the available data.It would be important to reach a general consensus on their diagnosis in order to construct a classification that remains stable over time and facilitates the design of clinical trials that,due to their low incidence,will require long recruitment periods.

Analysis of a passive ankle exoskeleton for reduction of metabolic costs during walking

Modern conflicts demand substantial physical and psychological exertion,often resulting in fatigue and diminished combat or operational readiness.Several exoskeletons have been developed recently to address these challenges,presenting various limitations that affect their operational or everyday usability.This article evaluates the performance of a dual-purpose passive ankle exoskeleton developed for the reduction of metabolic costs during walking,seeking to identify a force element that could be applied to the target population.Based on the 6-min walk test,twenty-nine subjects participated in the study using three different force elements.The results indicate that it is possible to reduce metabolic expenditure while using the developed exoskeleton.Additionally,the comfort and range of motion results verify the exoskeleton's suitability for use in uneven terrain and during extended periods.Nevertheless,the choice of the force element should be tailored to each user,and the control system should be adjustable to optimise the exoskeleton's performance.

Outpatient management of obscure gastrointestinal bleeding:A new perspective in high-risk patients

Mid-gastrointestinal bleeding accounts for approximately 5%-10%of all gastrointestinal bleeding cases,and vascular lesions represent the most frequent cause.The rebleeding rate for these lesions is quite high(about 42%).We hereby recommend that scheduled outpatient management of these patients could reduce the risk of rebleeding episodes.

Dynamic contrast enhanced ultrasound in differential diagnosis of hepatocellular carcinoma: A systematic review and meta-analysis

BACKGROUND Non-invasive differential diagnosis between hepatocellular carcinoma(HCC)and other liver cancer(i.e.cholangiocarcinoma or metastasis)is highly challenging and definitive diagnosis still relies on histological exam.The patterns of enhancement and wash-out of liver nodules can be used to stratify the risk of malignancy only in cirrhotic patients and HCC frequently shows atypical features.Dynamic contrast-enhanced ultrasound(DCEUS)with standardized software could help to overcome these obstacles,providing functional and quantitative parameters and potentially improving accuracy in the evaluation of tumor perfusion.AIM To explore clinical evidence regarding the application of DCEUS in the differential diagnosis of liver nodules.METHODS A comprehensive literature search of clinical studies was performed to identify the parameters of DCEUS that could relate to histological diagnosis.In accordance with the study protocol,a qualitative and quantitative analysis of the evidence was planned.RESULTS Rise time was significantly higher in HCC patients with a standardized mean difference(SMD)of 0.83(95%CI:0.48-1.18).Similarly,other statistically significant parameters were mean transit time local with a SMD of 0.73(95%CI:0.20-1.27),peak enhancement with a SMD of 0.37(95%CI:0.03-0.70),area wash-in area under the curve with a SMD of 0.47(95%CI:0.13-0.81),wash-out area under the curve with a SMD of 0.55(95%CI:0.21-0.89)and wash-in and wash-out area under the curve with SMD of 0.51(95%CI:0.17-0.85).SMD resulted not significant in fall time and wash-in rate,but the latter presented a trend towards greater values in HCC compared to intrahepatic cholangiocarcinoma.CONCLUSION DCEUS could improve non-invasive diagnosis of HCC,leading to less liver biopsy and early treatment.This quantitative analysis needs to be applied on larger cohorts to confirm these preliminary results.

Interleukin 1βreceptor and synaptic dysfunction in recurrent brain infection with Herpes simplex virus type-1

Several experimental evidence suggests a link between brain Herpes simplex virus type-1 infection and the occurrence of Alzheimer’s disease.However,the molecular mechanisms underlying this association are not completely understood.Among the molecular mediators of synaptic and cognitive dysfunction occurring after Herpes simplex virus type-1 infection and reactivation in the brain neuroinflammatory cytokines seem to occupy a central role.Here,we specifically reviewed literature reports dealing with the impact of neuroinflammation on synaptic dysfunction observed after recurrent Herpes simplex virus type-1 reactivation in the brain,highlighting the role of interleukins and,in particular,interleukin 1βas a possible target against Herpes simplex virus type-1-induced neuronal dysfunctions.

Soil resilience assessment using soil profile descriptions and Analytic Hierarchy Process in Mediterranean mountains considering diverse fire occurrences

Wildfires are complex natural phenomena that exert significant impacts on landscapes,societies,and economies.Understanding the concept of resilience is crucial in mitigating its possible negative impacts,as it involves preparing for,responding to,and recovering from wildfires.This research aims to demonstrate the utility of in situ soil profile description in assessing land use resilience using an Analytic Hierarchy Process(AHP)through an expert panel survey.The study examines a catchment located in the Balearic Islands,considering two fire occurrences(once and twice),comparing abandoned agricultural terraces and natural hillslopes.The results demonstrated that the priority ranking of variables to assess soil profile resilience against wildfires,determined by a panel of 10 experts,identified horizon depth(25.1%),slope inclination(21.5%),and hydrological connectivity(16.6%)as the most crucial factors.Other variables,such as number and size of roots,structure of pedal soil material,size class structure,and rock fragments,also contributed to resilience but to a lesser extent,with scores ranging from 5.7%to 9.6%.Analyzing the priorities established by the experts using AHP,the results showed that the least resilient soil horizon was H1 of the control hillslope,especially under high and low connectivity processes,which aligned with the loss of superficial soil horizons after one and two wildfires.Hillslopes showed greater changes in resilience after occurring wildfires compared to terraces,with the most significant alterations occurring after the second wildfire event.This study addresses a significant knowledge gap in the field by highlighting the interconnectedness of wildfires,resilience,and land use,providing insights into land management strategies for wildfire-prone regions.

Colon cancer screening:What to choose?

Colorectal cancer is one of the predominant tumors in the world,primarily generated by a progression from polyp to cancer which can last several years,giving a great opportunity to the scientific community for its prevention by screening programs that can be done with invasive and non-invasive tests.In this issue,Lopes et al show us an excellent review of screening,its options,its advantages and disadvantages.

From the mathematical model to the patient: The scientific and human aspects of artificial intelligence in gastrointestinal surgery

Recent medical literature shows that the application of artificial intelligence(AI)models in gastrointestinal pathology is an exponentially growing field,with pro-mising models that show very high performances.Regarding inflammatory bowel disease(IBD),recent reviews demonstrate promising diagnostic and prognostic AI models.However,studies are generally at high risk of bias(especially in AI models that are image-based).The creation of specific AI models that improve diagnostic performance and allow the establishment of a general prognostic fo-recast in IBD is of great interest,as it may allow the stratification of patients into subgroups and,in turn,allow the creation of different diagnostic and therapeutic protocols for these patients.Regarding surgical models,predictive models of post-operative complications have shown great potential in large-scale studies.In this work,the authors present the development of a predictive algorithm for early post-surgical complications in Crohn's disease based on a Random Forest model with exceptional predictive ability for complications within the cohort.The pre-sent work,based on logical and reasoned,clinical,and applicable aspects,lays a solid foundation for future prospective work to further develop post-surgical prognostic tools for IBD.The next step is to develop in a prospective and mul-ticenter way,a collaborative path to optimize this line of research and make it applicable to our patients.

Periodontal disease:A silent factor in the development and progression of diabetic retinopathy

The global increase in the prevalence of type 2 diabetes mellitus(T2DM)and its complications presents significant challenges to public health.Recently,periodontal disease(PD)was recognized as a factor that is likely to influence the progression of T2DM and its complications due to its potential to exacerbate systemic inflammation and oxidative stress.In this editorial,we comment on the article published by Thazhe Poyil et al in the very recent issue of the World Journal of Diabetes in 2024,which investigated the correlation between PD and diabetic retinopathy(DR)in T2DM patients,with emphasis on the association between periodontal swollen surface area,glycated hemoglobin(HbA1c),interleukin-6(IL-6),and lipoprotein(a).The findings by Thazhe Poyil et al are significant as they demonstrate a strong link between PD and DR in T2DM patients.This correlation highlights the importance of addressing periodontal health in diabetes management to potentially reduce the risk and severity of DR,a complication of diabetes.The integration of periodontal evaluation and treatment into diabetes care protocols may lead to improved glycemic control and better overall outcomes for T2DM patients.A few studies have established an interconnection between PD and diabetic complication,specifically DR,in T2DM patients,which we aim to highlight in this editorial.Emphasis was placed on the different mechanisms that suggest a bidirectional relationship between PD and T2DM,where the presence of periodontal inflammation negatively influenced glycemic control and contributed to the development and progression of DR through shared inflammatory and vascular mechanisms.This article highlights the importance of collaboration amongst diabetes specialists,ophthalmologists,periodontists,and public health professionals to advance the prevention,early detection,and treatment of PD and DR.This will improve the health and quality of life of T2DM patients.Moreover,the editorial highlights the need for further research on the specific molecular and immunological mechanisms that underlie the link between periodontitis and DR,with identification of common inflammatory biomarkers and signaling pathways.This is expected to facilitate effective direction of therapeutic objectives,thereby improving the management of diabetes and its complications through integrated care that incorporates oral health.

Minimally Invasive Surgery for Necrotizing Pancreatitis: A Case Report

Introduction: Necrotizing pancreatitis management is complex and varies significantly among clinicians. Minimally invasive approaches like transgastric necrosectomy via laparoscopy are emerging as effective treatment options. This case report underscores the technique’s efficacy, clinical outcomes, and role in reducing complications. Clinical Observation: A 59-year-old male with a history of smoking and alcoholism presented with severe abdominal pain, nausea, and vomiting. Over the following weeks, he developed symptoms including asthenia, weight loss, and melena. Diagnostic workup revealed severe anemia and Balthazar E necrotizing pancreatitis, with significant intra-abdominal fluid collections and signs of infection. After initial conservative management, the patient underwent transgastric necrosectomy via laparoscopy due to deteriorating clinical status. The procedure involved removing necrotic tissue and performing a cystogastroanastomosis and jejunostomy. Postoperative care included fasting, parenteral nutrition, broad-spectrum antibiotics, and enzymatic replacement. The patient recovered well, with reduced necrotic tissue on follow-up imaging, and was discharged twelve days post-surgery [1]. Conclusion: Transgastric necrosectomy by laparoscopy is a valuable first-line surgical option for patients with symptomatic necrotizing pancreatitis, particularly in cases without prior interventions. This minimally invasive technique helps reduce major complications and mortality, offering a less invasive alternative to traditional open necrosectomy. The multidisciplinary approach and careful postoperative management were crucial to the patient’s favorable outcome. The case highlights the potential of transgastric necrosectomy as an effective treatment strategy in managing complex pancreatitis cases, including those with associated duodenal perforation [2].

HVSR analysis of pumice sands for sediment depth characterization:A case study for Guadalajara,Mexico

The horizontal to vertical spectral ratio(HVSR)methodology is used here to characterize pumice soils and to image the three-dimensional surface geometry of Guadalajara,Mexico.Similar to other Latin American cities,Guadalajara is exposed to high seismic risk,with the particularity of being the largest urban settlement in Latin America built on pumice soils.Methodology has not yet been tested to characterize subsoil depths in pumice sands.Due to the questionable use of traditional geotechnical tests for the analysis of pumice soils,HVSR provides an alternative for its characterization without altering its fragile and porous structure.In this work,resonance frequency(F0)and peak amplitude(A0)are used to constrain the depth of the major impedance contrast that represents the interface between bedrock and pumice soil.Results were compared with borehole depths and other available geotechnical and geophysical data and show good agreement.One of the profiles estimated on the riverbanks that cross the city,reveals different subsoil thickness that could have an impact on different site responses on riverine areas to an eventual earthquake.Government and academic efforts are combined in this work to characterize depth sediments,an important parameter that impacts the regulations for construction in the city.

Microsurgical management of radicular cyst using guided tissue regeneration technique:A case report

BACKGROUND Radicular cyst is a lesion of odontogenic origin that arises from epithelial remains due to periapical periodontitis caused by inflammatory reactions generated at the apex of affected teeth with infected or necrotic pulps.The therapeutic mana gement of radicular cysts is controversial.There is only one case report of enucleation of a radicular cyst managed with microsurgery and apicoectomy,but without the use of the guided tissue regeneration(GTR)technique in the same surgical procedure.The present clinical case describes the management of a radicular cyst with microsurgical approach,performance of an apicoectomy of the tooth associated with the entity,application of GTR technique,use of a resorbable membrane of type I bovine collagen,and bovine xenograft.CASE SUMMARY A 68-year-old patient presented with a radicular cyst from an upper lateral incisor.The microsurgical management used was aimed at enucleating the chemical membrane,performing apicoectomy of the tooth along with careful and precise retrograde filling,and implementing GTR technique using a resorbable collagen membrane and bovine xenograft.The diagnosis of radicular cyst was confirmed using histopathological analysis.The patient underwent follow-up evaluations at 10 and 30 d postoperatively.At 4 months postoperative evaluation,she remained asymptomatic,and radiographs showed significant periapical healing with adequate bone formation.CONCLUSION These results suggest that microsurgical management using the GTR technique with collagen membrane and xenograft,contributes to bone regeneration.