Combinatorial therapies for spinal cord injury repair

Spinal cord injuries have profound detrimental effects on individuals, regardless of whether they are caused by trauma or non-traumatic events. The compromised regeneration of the spinal cord is primarily attributed to damaged neurons, inhibitory molecules, dysfunctional immune response, and glial scarring. Unfortunately, currently, there are no effective treatments available that can fully repair the spinal cord and improve functional outcomes. Nevertheless, numerous pre-clinical approaches have been studied for spinal cord injury recovery, including using biomaterials, cells, drugs, or technological-based strategies. Combinatorial treatments, which target various aspects of spinal cord injury pathophysiology, have been extensively tested in the last decade. These approaches aim to synergistically enhance repair processes by addressing various obstacles faced during spinal cord regeneration. Thus, this review intends to provide scientists and clinicians with an overview of pre-clinical combinatorial approaches that have been developed toward the solution of spinal cord regeneration as well as update the current knowledge about spinal cord injury pathophysiology with an emphasis on the current clinical management.

Secretome of polarized macrophages:potential for targeting inflammatory dynamics in spinal cord injury

Spinal cord injury(SCI)involves an initial traumatic phase,followed by secondary events such as ischemia,increased blood-spinal cord barrier permeability,ionic disruption,glutamate excitotoxicity,and metabolic alterations.A pe rsistent and exagge rated inflammato ry response within the spinal cord accompanies these events(Lima et al.,2022).The complexity and interplay of these mechanisms exacerbate the initial injury,leading to a degenerative process at the injury site.While the initial trauma is unavoidable,the secondary injury begins within minutes and can last for months,creating an optimal window for therapeutic intervention.

The Perception of Health Workers and Stakeholders Involved in the Process of Selecting Indigent in Burkina Faso

Background: Indigent selected for their health care is complex and poses enormous challenges. The actors involved have an influence on health actions and their perception is decisive for better care for the indigent. Little evidence exists on these perceptions and this paper has captured this. Methods: A case study involved 163 participants with a questionnaire and an interview guide. The quantitative responses were classified according to a measurement scale, proportions and overall indices of perception (Ip) and satisfaction (CSAT) were calculated. The relationship between variables was investigated using chi-square. Thematic analysis was used with qualitative data. The study met ethical requirements. Results: The participants had a positive perception of the selection: Ip = 0.77, but a minority (1/5) were dissatisfied with the selection. The perception of selection did not differ significantly depending on the experience of the actors. For the vast majority, the definition of indigent was satisfactory (CSAT = 91.4). The selection was done in a top down fashion and steps such as setting up committees, informing stakeholders, had shortcomings which negatively impacted the effectiveness of the selection. The needs of the participants included transparency in the indigent select process, matching the tools for selecting the indigent to the context, strengthening of local action, deconstruction of prejudices in terms of the indigent, power of actors to act, and importance for health services to reach out to the indigent. Conclusion: Considering the perception of the actors as well as their needs will improve the selection for effective care of the indigent.

Preliminary Study on Renal Ultrasound Biometry in Apparently Healthy 18 to 30-Year-Old Subjects with Normal Renal Function in Ouagadougou

Introduction: In our practice, renal measurements in patients with normal renal function usually appear to be lower compared to standards reported in reference literature. The standards are probably different in our context. Given the importance of renal biometrics in nephrological practice, we felt it necessary to carry out this preliminary study in order to identify an order of reference measurements appropriate to our context. Methods: This was a cross-sectional study that took place from 18 August to 04 November 2018 at the Yalgado Ouedrarogo University Hospital Center. The first 100 subjects aged between 18 and 30 years who met the following inclusion criteria were selected: to be black african Burkinabe and to have normal renal function. The height, width and thickness of each kidney were measured using ultra-sound scanners. For statistical tests, a value of p < 0.05 was considered statistically significant. Results: The average age was 23.9 ± 6.1 years and the sex ratio was 2.2. Mean heights, widths and renal thicknesses were 94.5 ± 14.5, 38.7 ± 10.7 and 36.3 ± 10.3 mm, and 96.7 ± 16.7, 42.7 ± 16.7 and 36.8 ± 10.8 mm respectively for right and left kidneys. The distribution of the different renal dimensions in our sample followed a normal distribution. In the particular case of the right kidney, the probability that its height was between 79.2 and 109.7 mm was 0.95 and the probability that it was less than 79.2 mm or greater than 109.7 mm was 0.05. Renal height was significantly higher in subjects with height greater than 1.70 m (p ≤ 0.02). The left kidneys were on average significantly larger than the right kidneys (p = 0.0001). Conclusions: Our study is not extrapolable to the general population of Burkina Faso. It suggests, however, that the kidneys of the apparently healthy Burkinabe subject are smaller than what is reported in anatomy reference books. Our work, which is preliminary, should be deepened through a national survey. In the meantime, we should consider, in the nephrological assessment of the Burkinabe patient, the results of the renal biometrics we report.

Factors associated with mothers’health care-seeking behaviours for childhood fever in Burkina Faso:findings from repeated cross-sectional household surveys

Introduction:Fever is one of the most frequent reasons for paediatric consultations in Burkina Faso,but health care-seeking behaviours and the factors associated with health care-seeking in the event of childhood fever are poorly documented.This study aims to analyse the health care-seeking behaviours and the factors associated with health care-seeking for childhood fever in Burkina Faso.Methods:This study used the data from the baseline and endline surveys conducted to evaluate the impact of the Performance-Based Financing program in Burkina Faso.Univariate and multivariate binary logistic regression analyses were used to identify the factors associated with appropriate healthcare-seeking for childhood fever.Odds ratios were estimated to assess the strength of associations and 95%confidence intervals(CIs)were used for significance tests.Data were cleaned,coded and analysed using Stata software version 16.1.Results:Among the children under five who had a fever,75.19%and 79.76%sought appropriate health care in 2013 and 2017,respectively.Being 24-59 months old(AOR:0.344,95%CI 0.182-0.649 in 2013 and AOR:0.208,95%CI 0.115-0.376 in 2017),living in a very wealthy household(AOR:2.014,95%CI 1.149-3.531 in 2013 and AOR:2.165,95%CI 1.223-3.834 in 2017),having a mother with a secondary or higher level of education or having made at least four antenatal care visits were significantly associated with seeking appropriate health care for childhood fever.Living in an area where the health facility is safe was also significantly associated with seeking appropriate care for childhood fevers.Conclusions:The findings underscore the need to concentrate efforts aiming at sensitizing the population(especially women of childbearing age)to improve sanitation and the use of family planning(household composition),skilled antenatal care and postnatal care to help reduce the prevalence of fever in children under five and improve the use of medical healthcare for childhood fever.

Capsule endoscopy and panendoscopy:A journey to the future of gastrointestinal endoscopy

In 2000,the small bowel capsule revolutionized the management of patients with small bowel disorders.Currently,the technological development achieved by the new models of double-headed endoscopic capsules,as miniaturized devices to evaluate the small bowel and colon[pan-intestinal capsule endoscopy(PCE)],makes this non-invasive procedure a disruptive concept for the management of patients with digestive disorders.This technology is expected to identify which patients will require conventional invasive endoscopic procedures(colonoscopy or balloon-assisted enteroscopy),based on the lesions detected by the capsule,i.e.,those with an indication for biopsies or endoscopic treatment.The use of PCE in patients with inflammatory bowel diseases,namely Crohn’s disease,as well as in patients with iron deficiency anaemia and/or overt gastrointestinal(GI)bleeding,after a non-diagnostic upper endoscopy(esophagogastroduodenoscopy),enables an effective,safe and comfortable way to identify patients with relevant lesions,who should undergo subsequent invasive endoscopic procedures.The recent development of magnetically controlled capsule endoscopy to evaluate the upper GI tract,is a further step towards the possibility of an entirely non-invasive assessment of all the segments of the digestive tract,from mouth-to-anus,meeting the expectations of the early developers of capsule endoscopy.

Alpha-1 antitrypsin deficiency and Pi^(*)Z allele as important co-factors in the development of liver fibrosis

BACKGROUND Alpha-1 antitrypsin deficiency(AATD)is a codominant autosomal hereditary condition that predisposes patients to the development of lung and/or liver disease,and Pi*Z allele is the most clinically relevant mutation.AIM To evaluate the impact of clinical parameters and AATD phenotypes,particularly the Pi*Z allele,in liver fibrosis.METHODS Cross-sectional cohort study including consecutive patients with AATD followed in Pulmonology or Hepatology consultation.RESULTS Included 69 patients,49.3%had Pi*MZ phenotype and 10.1%Pi*ZZ.An age≥55 years,age at diagnosis≥41 years and AAT at diagnosis<77 mg/dL predicted a nonalcoholic fatty liver disease fibrosis score(NFS)not excluding advanced fibrosis[area under the curve(AUC)=0.840,P<0.001;AUC=0.836,P<0.001;AUC=0.681,P=0.025].An age≥50 years and age at diagnosis≥41 years predicted a fibrosis-4 index of moderate to advanced fibrosis(AUC=0.831,P<0.001;AUC=0.795,P<0.001).Patients with hypertension,type 2 diabetes mellitus(DM),dyslipidaemia,metabolic syndrome,and regular alcohol consumption were more likely to have a NFS not excluding advanced fibrosis(P<0.001,P=0.002,P=0.008,P<0.001,P=0.033).Patients with at least one Pi*Z allele and type 2 DM were 8 times more likely to have liver stiffness measurement≥7.1 kPa(P=0.040).CONCLUSION Risk factors for liver disease in AATD included an age≥50 years,age at diagnosis≥41 years,metabolic risk factors,regular alcohol consumption,at least one Pi*Z allele,and AAT value at diagnosis<77 mg/dL.We created an algorithm for liver disease screening in AATD patients to use in primary care,selecting those to be referred to Hepatology consultation.

Study of the Mineral Element Status in Sickle Cell Patients Attending the Mixed Medicine and Sickle Cell Anemia Center “Yolo Mabanga” in Kinshasa in Democratic Republic of the Congo

Introduction: Sickle cell disease, also called sickle cell anemia, is a genotypic disorder prevalent in the black population;it is characterized by a hemolytic type anemia and can worsen following a deficiency of copper, zinc and serum iron. Methods: It was a question of evaluating the plasma status of copper and zinc by the photometric method, serum iron was measured by spectrophotometry, and finally ferritin and transferrin were measured by the immunoenzymatic method;in subjects with sickle cell disease and healthy subjects of all ages followed at the mixed medicine and sickle cell anemia center in Kinshasa (CMMASS). Results: A total of 60 subjects participated in this study. The sex ratio was 1.30;the average age of sickle cell patients was 7.4 years ± 3.8 and 27.4 years ± 5.1;for the control group, the average age was 8.2 years ± 4.2 and 29 years ± 6.7. 13.3% of children with sickle cell disease presented hypocupremia and 13.3% hypercupremia. For adults with sickle cell disease, 26.7% had hypocupremia and 13% had hypercupremia. Regarding zincemia, 67% of children and adults with sickle cell disease presented hypozincemia;60% of child subjects with sickle cell desease demonstrated hyposideremia;in adults with sickle cell desease 20% have hyposideremia and 13% have hypersideremia. Conclusion: Our results demonstrate not only the effective presence of iron overload in adult sickle cell patients, but also an iron deficiency in controls and sickle cell patients, ignoring hemolysis. .

Genetic diversity and occult hepatitis B infection in Africa: A comprehensive review

BACKGROUND Occult hepatitis B infection(OBI)is a globally prevalent infection,with its frequency being influenced by the prevalence of hepatitis B virus(HBV)infection in a particular geographic region,including Africa.OBI can be transmitted th-rough blood transfusions and organ transplants and has been linked to the development of hepatocellular carcinoma(HCC).The associated HBV genotype influences the infection.AIM To highlight the genetic diversity and prevalence of OBI in Africa.METHODS This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and involved a comprehensive search on PubMed,Google Scholar,Science Direct,and African Journals Online for published studies on the prevalence and genetic diversity of OBI in Africa.RESULTS The synthesis included 83 articles,revealing that the prevalence of OBI varied between countries and population groups,with the highest prevalence being 90.9%in patients with hepatitis C virus infection and 38%in blood donors,indicating an increased risk of HBV transmission through blood transfusions.Cases of OBI reactivation have been reported following chemotherapy.Genotype D is the predominant,followed by genotypes A and E.CONCLUSION This review highlights the prevalence of OBI in Africa,which varies across countries and population groups.The study also demonstrates that genotype D is the most prevalent.

Geographical Distribution of Arboviruses, Aedes aegypti and Aedes albopictus Vectors and Their Resistance to Insecticides in Africa: A Systematic Review

Background & Objectives: Epidemics of arboviruses such as Dengue, Chikungunya and Zika have been recorded in recent years indicating that Aedes aegypti and Aedes albopictus are both important and very active vectors in Africa. For vector control, insecticides are on the front line, unfortunately, reported resistance jeopardizes the effectiveness of this strategy. The objective of this review was to determine the geographical distribution and insecticide resistance mechanisms of Ae. aegypti and Ae. Albopictus in Africa. Methods: A systematic review of the literature in scientific databases (PubMed, Google Scholar, ScienceDirect, Hinari) allowed us to identify relevant articles on the geographical distribution of Aedes aegypti, Aedes albopictus and arboviral diseases. On the other hand, studies related to insecticides used in vector control against Aedes, associated resistances and their molecular and metabolic mechanisms. Results: A total of 94 studies met the inclusion criteria for this search. Aedes aegypti is reported in most of Africa, and Aedes albopictus in part. There is a re-emergence and outbreak of Arbovirus epidemics in West and Central Africa. The insecticides used were organochlorines, carbamates, organophosphates and pyrethroids. In Aedes, target site insensitivity and metabolic resistance would be the 2 main mechanisms of resistance to these insecticides. Interpretation & Conclusion: Resistance has been recorded in all four major classes of insecticides recommended by WHO for vector control and eradication. New vector control methods such as the use of plant extracts with larvicidal and adulticidal activities, advanced modern biotechnology techniques, and nanobiotechnology need to be developed.

Serrated pathway in colorectal carcinogenesis

Serrated adenocarcinoma is a recently described subset of colorectal cancer(CRC),which account for about10%of all CRCs and follows an alternative pathway in which serrated polyps replace the traditional adenoma as the precursor lesion to CRC.Serrated polyps form a heterogeneous group of colorectal lesions that includes hyperplastic polyps(HPs),sessile serrated adenoma(SSA),traditional serrated adenoma(TSA)and mixed polyps.HPs are the most common serrated polyp followed by SSA and TSA.This distinct histogenesis is believed to have a major influence in prevention strategies,patient prognosis and therapeutic impact.Genetically,serrated polyps exhibited also a distinct pattern,with KRAS and BRAF having an important contribution to its development.Two other molecular changes that have been implicated in the serrated pathway include microsatellite instability and the CpG island methylator phenotype.In the present review we will address the current knowledge of serrated polyps,clinical pathological features and will update the most recent findings of its molecular pathways.The understanding of their biology and malignancy potential is imperative to implement a surveillance approach in order to prevent colorectal cancer development.

Combinatorial therapies for spinal cord injury: strategies to induce regeneration

Spinal cord injury(SCI)is a condition without treatment,mainly characterized by the loss of motor and sensory function below the level of injury.This is accompanied by several complications such as cardiac and respiratory compromise,and often patients present psychological ailments associated with the drastic alteration of their normal lifestyle.SCI pathophysiology derives from a massive damage to the spinal cord tissue,which is propagated

Role of endoglin and VEGF family expression in colorectal cancer prognosis and anti-angiogenic therapies

Colorectal cancer(CRC)is one of the cancer models and most of the carcinogenic steps are presently well understood.Therefore,successful preventive measures are currently used in medical practice.However,CRC is still an important public health problem as it is the third most common cancer and the fourth most frequent cause of cancer death worldwide.Nowadays,pathologic stage is a unique and well-recognized prognostic indicator,however,more accurate indicators of the biologic behavior of CRC are expected to improve the specificity of medical treatment.Angiogenesis plays an important role in the growth and progression of cancer but its role as a prognostic factor is still controversial.Probably the most important clinical implication of tumor angiogenesis is the development of anti-angiogenic therapy.The goal of this review is to critically evaluate the role of angiogenic markers,assessed by either endoglin-related microvessel density or expression of vascular endothelial growth factor family members in the CRC setting and discuss the role of these angiogenic markers in antiangiogenic therapies.

Endoscopic retrograde cholangiopancreatography for suspected choledocholithiasis: From guidelines to clinical practice

AIM: To study the practical applicability of the American Society for Gastrointestinal Endoscopy guidelines in suspected cases of choledocholithiasis.METHODS: This was a retrospective single center study, covering a 4-year period, from January 2010 to December 2013. All patients who underwent endoscopic retrograde cholangiopancreatography(ERCP) for suspected choledocholithiasis were included. Based on the presence or absence of predictors of choledocholithiasis(clinical ascending cholangitis, common bile duct(CBD) stones on ultrasonography(US), total bilirubin > 4 mg/d L, dilated CBD on US, total bilirubin 1.8-4 mg/d L, abnormal liver function test, age > 55 years and gallstone pancreatitis), patients were stratified in low, intermediate or high risk for choledocholithiasis. For each predictor and risk group we used the χ2 to evaluate the statistical associations with the presence of choledocolithiasis at ERCP. Statistical analysis was performed using SPSS version 21.0. A P value of less than 0.05 was considered statistically significant. RESULTS: A total of 268 ERCPs were performed for suspected choledocholithiasis. Except for gallstone pancreatitis(P = 0.063), all other predictors of cho-ledocholitiasis(clinical ascending cholangitis, P = 0.001; CBD stones on US, P ≤ 0.001; total bilirubin > 4 mg/dL, P = 0.035; total bilirubin 1.8-4 mg/dL, P = 0.001; dilated CBD on US, P ≤ 0.001; abnormal liver function test, P = 0.012; age > 55 years, P = 0.002) showed a statistically significant association with the presence of choledocholithiasis at ERCP. Approximately four fifths of patients in the high risk group(79.8%, 154/193 patients) had confirmed choledocholithiasis on ERCP, vs 34.2%(25/73 patients) and 0(0/2 patients) in the intermediate and low risk groups, respectively. The definition of "high risk group" had a sensitivity of 86%, positive predictive value 79.8% and specificity 56.2% for the presence of choledocholithiasis at ERCP. CONCLUSION: The guidelines should be considered to optimize patients' selection for ERCP. For high risk patients specificity is still low, meaning that some patients perform ERCP unnecessarily.

Mesenchymal stem cells secretome:current trends and future challenges

Mesenchymal stem cells(MSCs)secretome:a good candidate for medical biotechnology?Medical biotechnology is currently defined as the application of biotechnological tools for producing multiple technologies and products to health care,becoming an important bridge between different fields,namely neuroscience,regenerative medicine,pharmacology and bio-engineering(Pham,2018).The use and manipulation of stem cells can potentially represent a medical biotechnology breakthrough that brings regenerative medicine to a new era.Actually,over the last decade,the use of stem cells has remarkably been proposed as a regenerative tool,and within it,MSCs have emerged as a promising therapeutic option.

Upper gastrointestinal bleeding risk scores： Who, when andwhy？

Upper gastrointestinal bleeding(UGIB) remains a significant cause of hospital admission. In order to stratify patients according to the risk of the compli-cations, such as rebleeding or death, and to predict the need of clinical intervention, several risk scores have been proposed and their use consistently recommended by international guidelines. The use of risk scoring systems in early assessment of patients suffering from UGIB may be useful to distinguish high-risks patients, who may need clinical intervention and hospitalization, from low risk patients with a lower chance of developing complications, in which management as outpatients can be considered. Although several scores have been published and validated for predicting different outcomes, the most frequently cited ones are the Rockall score and the Glasgow Blatchford score(GBS). While Rockall score, which incorporates clinical and endoscopic variables, has been validated to predict mortality, the GBS, which is based on clinical and laboratorial parameters, has been studied to predict the need of clinical intervention. Despite the advantages previously reported, their use in clinical decisions is still limited. This review describes the different risk scores used in the UGIB setting, highlights the most important research, explains why and when their use may be helpful, reflects on the problems that remain unresolved and guides future research with practical impact.

Finding the solution for incomplete small bowel capsule endoscopy

AIM:To evaluate whether the use of real time viewer(RTV)and administration of domperidone to patients with delayed gastric passage of the capsule could reduce the rate of incomplete examinations(IE)and improve the diagnostic yield of small bowel capsule endoscopy(SBCE).METHODS:Prospective single center interventional study,from June 2012 to February 2013.Capsule location was systematically checked one hour after ingestion using RTV.If it remained in the stomach,the patient received 10 mg domperidone per os and the location of the capsule was rechecked after 30 min.If the capsule remained in the stomach a second dose of10 mg of domperidone was administered orally.After another 30 min the position was rechecked and if the capsule remained in the stomach,it was passed into the duodenum by upper gastrointestinal(GI)endoscopy.The rate of IE and diagnostic yield of SBCE were compared with those of examinations performed before the use of RTV or domperidone in our Department(control group,January 2009-May 2012).RESULTS:Both groups were similar regarding age,sex,indication,inpatient status and surgical history.The control group included 307 patients,with 48(15.6%)IE.The RTV group included 82 patients,with3(3.7%)IE,P=0.003.In the control group,average gastric time was significantly longer in patients with IE than in patients with complete examination of the small bowel(77 min vs 26 min,P=0.003).In the RTV group,the capsule remained in the stomach one hour after ingestion in 14/82 patients(17.0%)vs 48/307(15.6%)in the control group,P=0.736.Domperidone did not significantly affect small bowel transit time(260min vs 297 min,P=0.229).The capsule detected positive findings in 39%of patients in the control group and 49%in the RTV group(P=0.081).CONCLUSION:The use of RTV and selective administration of domperidone to patients with delayed gastric passage of the capsule significantly reduces incomplete examinations,with no effect on small bowel transit time or diagnostic yield.

From regenerative strategies to pharmacological approaches:can we fine-tune treatment for Parkinson's disease?

Parkinson's disease is the second most prevalent neurodegenerative disorder worldwide.Clinically,it is characterized by severe motor complications caused by progressive degeneration of dopaminergic neurons.Current treatment is focused on mitigating the symptoms through the administration of levodopa,rather than on preventing dopaminergic neuronal damage.Therefore,the use and development of neuroprotective/disease-modifying strategies is an absolute need that can lead to promising gains on translational research of Parkinson's disease.For instance,N-acetylcysteine,a natural compound with strong antioxidant effects,has been shown to modulate oxidative stress,preventing dopamine-induced cell death.Despite the evidence of neuroprotective and modulatory effects of this drug,as far as we know,it does not induce per se any regenerative process.Therefore,it would be of interest to combine the latter with innovative therapies that induce dopaminergic neurons repair or even differentiation,as stem cell-based strategies.Stem cells secretome has been proposed as a promising therapeutic approach for Parkinson's disease,given its ability to modulate cell viability/preservation of dopaminergic neurons.Such approach represents a shift in the paradigm,showing that cell-transplantation free therapies based on the use of stem cells secretome may represent a potential alternative for regenerative medicine of Parkinson's disease.Thus,in this review,we address the current understanding of the potential combination of stem cell free-based strategies and neuroprotective/disease-modifying strategies as a new paradigm for the treatment of central nervous system neurodegenerative diseases,like Parkinson's disease.

Relationship between Fusobacterium nucleatum,inflammatory mediators and microRNAs in colorectal carcinogenesis

AIM To examine the effect of Fusobacterium nucleatum(F. nucleatum) on the microenvironment of colonic neoplasms and the expression of inflammatory mediators and microRNAs(miRNAs).METHODS Levels of F. nucleatum DNA, cytokine gene mRNA(TLR2, TLR4, NFKB1, TNF, IL1 B, IL6 and IL8), and potentially interacting miRNAs(miR-21-3p, miR-22-3p, mi R-28-5p, miR-34a-5p, miR-135b-5p) were measured by quantitative polymerase chain reaction(qPCR) TaqMan? assays in DNA and/or RNA extracted from the disease and adjacent normal fresh tissues of 27 colorectal adenoma(CRA) and 43 colorectal cancer(CRC) patients. KRAS mutations were detected by direct sequencing and microsatellite instability(MSI) status by multiplex PCR. Cytoscape v3.1.1 was used to construct the postulated miRNA:mRNA interaction network.RESULTS Overabundance of F. nucleatum in neoplastic tissue compared to matched normal tissue was detected in CRA(51.8%) and more markedly in CRC(72.1%). We observed significantly greater expression of TLR4, IL1 B, IL8, and miR-135 b in CRA lesions and TLR2, IL1 B, IL6, IL8, mi R-34 a and miR-135 b in CRC tumours compared to their respective normal tissues. Only two transcripts for miR-22 and miR-28 were exclusively downregulated in CRC tumour samples. The mRNA expression of IL1 B, IL6, IL8 and miR-22 was positively correlated with F. nucleatum quantification in CRC tumours. The mRNA expression of miR-135 b and TNF was inversely correlated. The miRNA:mRNA interaction network suggested that the upregulation of miR-34 a in CRC proceeds via a TLR2/TLR4-dependent response to F. nucleatum. Finally, KRAS mutations were more frequently observed in CRC samples infected with F. nucleatum and were associated with greater expression of miR-21 in CRA, while IL8 was upregulated in MSI-high CRC.CONCLUSION Our findings indicate that F. nucleatum is a risk factor for CRC by increasing the expression of inflammatory mediators through a possible mi RNA-mediated activation of TLR2/TLR4.

Natural orifice transluminal endoscopy surgery:A review

Minimally invasive surgery started spreading worldwide in 1987,when the first laparoscopic cholecystectomy was performed.Meanwhile,improvement of endoscopic equipment and instruments allowed gastroenterologists to attempt more aggressive endoluminal interventions,even beyond the wall barrier.The first transgastric peri-toneoscopy,in 2004,brought to light the concept of natural orifice transluminal endoscopic surgery(NOTES).The idea of incisionless surgery is attractive and has become a new goal for both surgeons and other people interested in this field of investigation.The authors present a review of all developments concerning NOTES,including animal studies and human experience.