Mesenchymal stem cell-conditioned medium accelerates regeneration of human renal proximal tubule epithelial cells after gentamicin toxicity

Bone marrow-derived mesenchymal stem cells (MSCs) have the capacity to regenerate renal tubule epithelia and repair renal function without fusing with resident tubular cells. The goal of the present project was to investigate the role of MSCs secreted cytokines on tubule cell viability and regeneration after a toxic insult, using a conditionally immortalized human proximal tubule epithelial cell (ciPTEC) line. Gentamicin was used to induce nephrotoxicity, and cell viability and migration were studied in absence and presence of human MSC-conditioned medium (hMSC-CM) i.e. medium containing soluble factors produced and secreted by MSCs. Exposure of ciPTEC to 0–3000 μg/ml gentamicin for 24 h caused a significant dose-dependent increase in cell death. We further demonstrated that the nephrotoxic effect of 2000 μg/ml gentamicin was recovered partially by exposing cells to hMSC-CM. Moreover, exposure of ciPTEC to gentamicin (1500–3000 μg/ml) for 7 days completely attenuated the migratory capacity of the cells. In addition, following scrape-wounding, cell migration of both untreated and gentamicin-exposed cells was increased in the presence of hMSC-CM, as compared to exposures to normal medium, indicating improved cell recovery. Our data suggest that cytokines secreted by MSCs stimulate renal tubule cell regeneration after nephrotoxicity.     

The effect of overbite and overjet on clinical parameters of periodontal disease: A case control study

AimTo investigate the association of overjet and overbite with clinical parameters of periodontal disease.Material and methodsThe study was performed in Riyadh, Saudi Arabia, from March 2017 to March 2018. 600 Saudi males aged 20–30 years old were included. Participants were divided into three groups (n: 200) depending on the presence of overjet (OJ) or overbite (OB) and its relationship with periodontal disease. Periodontal parameters were assessed clinically and radiographically. One-way analysis of variance was used to test for any significant differences between groups. Tukey’s post hoc comparison test was used to evaluate correlations among parameters.ResultsOJ exceeding 8 mm was correlated with debris, calculus, and periodontal scores on mandibular anterior teeth, especially on the lingual surfaces.Both OJ and OB groups showed significantly increased PD, compared to that of the control group in measurement at the lingual (P = 0.004, 0.003) and proximal (P = 0.002, 0.002) surfaces of the lower anterior teeth. Finally, the CEJ-AB was statistically significantly higher in the OB group compared to the OJ and control groups (P = 0.091, 0.008).ConclusionThe present study found a correlation between OJ and OB and periodontal disease, as measured using specific parameters. This indicates that periodontal treatment may be insufficient unless the overjet or overbite is corrected.     

Proximal Hamstring Tendinopathy: A Systematic Review of Interventions

BackgroundProximal hamstring tendinopathy affects athletic and non-athletic populations and is associated with longstanding buttock pain. The condition is common in track and field, long distance running and field-based sports. Management options need to be evaluated to direct appropriate clinical management.Purpose/HypothesisTo evaluate surgical and non-surgical interventions used in managing proximal hamstring tendinopathy.Study designSystematic reviewMethodsElectronic databases were searched to January 2019. Studies (all designs) investigating interventions for people with proximal hamstring tendinopathy were eligible. Outcomes included symptoms, physical function, quality of life and adverse events. Studies were screened for risk of bias. Reporting quality was assessed using the Cochrane Risk of Bias Tool (Randomized Controlled Trials [RCT]) and the Joanna Briggs Institute Checklist (Case Series). Effect sizes (Standard mean difference or Standard paired difference) of 0.2, 0.5 and 0.8 were considered as small, medium and large respectively. Overall quality of evidence was rated according to GRADE guidelines.ResultsTwelve studies (2 RCTs and 10 case series) were included (n=424; males 229). RCTs examined the following interventions: platelet-rich plasma injection (n=1), autologous whole-blood injection (n=1), shockwave therapy (n=1) and multi-modal intervention (n=1). Case series included evaluation of the following interventions: platelet-rich plasma injection (n=3), surgery (n=4), corticosteroid injection (n=2), multi-modal intervention + platelet-rich plasma injection (n=1). Very low-level evidence found shockwave therapy was more effective than a multi-modal intervention, by a large effect on improving symptoms (-3.22 SMD; 95% CI -4.28, -2.16) and physical function (-2.42 SMD; 95% CI-3.33, -1.50) in the long-term. There was very low-level evidence of no difference between autologous whole-blood injection and platelet-rich plasma injection on physical function (0.17 SMD; 95% CI -0.86, 1.21) to (0.24 SMD; 95% CI -0.76, 1.24) and quality of life (-0.04 SMD; 95%CI -1.05, 0.97) in the medium-term. There was very low-quality evidence that surgery resulted in a large reduction in symptoms (-1.89 SPD; 95% CI -2.36, -1.41) to (-6.02 SPD; 95% CI -8.10, -3.94) and physical function (-4.08 SPD; 95%CI -5.53, -2.63) in the long-term.ConclusionsThere is insufficient evidence to recommend any one intervention over another. A pragmatic approach would be to initially trial approaches proven successful in other tendinopathies.Level of evidenceLevel 2a     

Elevated IL-38 Serum Levels in Newly Diagnosed Multiple Sclerosis and Systemic Sclerosis Patients

ObjectiveInterleukin (IL)-38 is a newly discovered member of the IL-1 cytokine family with a proposed anti-inflammatory profile. We studied the probable role of this cytokine in the pathogenesis of two autoimmune diseases: multiple sclerosis (MS) and systemic sclerosis (SSc).Subjects and MethodsA total of 87 MS patients and 86 SSc patients (40 new and recently untreated cases and 46 treated cases) were selected for this study. Eighty-seven and 80 age- and sex-matched healthy subjects were included as controls for MS and SSc, respectively. Clinical and paraclinical features of the patients were recorded at the time of sampling. Serum IL-38 was measured by ELISA.ResultsLevels of serum IL-38 did not significantly differ between the total MS or SSc patients compared to controls. However, levels of IL-38 were significantly higher in newly diagnosed patients of MS (206.43 ± 38.97 pg/mL, p < 0.0001) than in those previously treated (158.04 ± 39.45 pg/mL). Similarly, new/recently untreated cases of SSc patients showed increased IL-38 levels (185.19 ± 36.27 pg/mL, p = 0.001) compared to treated patients (166.82 ± 33.08 pg/mL). IL-38 levels in newly diagnosed MS patients (p = 0.007) and new/recently untreated SSc patients (p = 0.032) were significantly higher than those in healthy controls.ConclusionThe higher serum levels of IL-38 in new or recently untreated cases of MS and SSc patients than in treated patients and healthy controls suggest the possible role of this cytokine in the development of these diseases or as part of a feedback loop to attenuate the inflammatory conditions in early stages of these diseases.     

Exploiting immunology and molecular genetics for rational vaccine design against tuberculosis.

One hundred years after the Nobel Prize was awarded to Robert Koch for his work on tuberculosis (TB) and 85 years after the development of the attenuated vaccine strain, Mycobacterium bovis bacille Calmette-Guérin (BCG), by Albert Calmette and Camille Guérin, effective prevention measures against TB are still not available. However, the first decade of the 21st century will witness the implementation of clinical trials with several novel vaccine candidates. These candidates fall into two groups: (1) subunit vaccines aimed at boosting the immune response induced by a BCG prime, and (2) recombinant (r)BCG improved to replace the current BCG vaccine strain. For boosting, protein and DNA vaccines in suitable adjuvant or delivery systems, respectively, as well as recombinant viral carriers, such as recombinant modified vaccinia virus Ankara, are being tested. For rBCG prime, a vaccine strain with higher immunogenicity and a strain overexpressing a dominant antigen have been developed. These vaccine candidates will have passed phase I clinical trials before the end of 2006. The goal for the future would be to have these novel vaccine candidates tested in different combinations to facilitate the design of the most efficacious vaccination protocol.     

Development and course of heart failure after a myocardial infarction in younger and older people

Background Acute myocardial infarction （AMI） is a common cause of heart failure （HF）, which can develop soon after AMI and may persist or resolve or develop late. HF after an MI is a major source of mortality. The cumulative incidence, prevalence and resolution of HF after MI in different age groups are poorly described. This study describes the natural history of HF after AMI according to age. Methods Patients with AMI during 1998 were identified from hospital records. HF was defined as treatment of symptoms and signs of HF with loop diuretics and was considered to have resolved if loop diuretic therapy could be stopped without recurrence of symptoms. Patients were cate- gorised into those aged 〈 65 years, 65-75 years, and 〉 75 years. Results Of 896 patients, 311,297 and 288 were aged 〈 65, 65-75 and 〉75 years and of whom 24%, 57% and 82% had died respectively by December 2005. Of these deaths, 24 （8%）, 68 （23%） and 107 （37%） oc- curred during the index admission, many associated with acute HF. A further 37 （12%）, 63 （21%） and 82 （29%） developed HF that persisted until discharge, of whom 15, 44 and 62 subsequently died. After discharge, 53 （24%）, 55 （40%） and 37 （47%） patients developed I-IF for the first time, of whom 26%, 62% and 76% subsequently died. Death was preceded by the development of HF in 35 （70%）, 93 （91%） and 107 （85%） in aged 〈 65 years, 65-75 years and 〉75 years, respectively. Conclusions The risk of developing HF and of dying after an MI in- creases progressively with age. Regardless of age, most deaths after a MI are preceded by the development of HF.     

Incidence of HCC in chronic hepatitis C patients with advanced hepatic fibrosis who achieved SVR following DAAs: A prospective study

Liver cirrhosis is an important risk factor for hepatocellular carcinoma. The reported annual incidence of HCC is about 3%‐8% in CHC cirrhotic patients. Based on the Cochrane systematic review, there was no clear evidence, on the long‐term clinical effects of DAAs in patients achieving SVR, as regard liver cirrhosis‐related HCC incidence. The aim of the study was to determine the incidence of HCC in chronic hepatitis C patients genotype IV with liver cirrhosis and advanced liver fibrosis after achieving SVR following DAA treatment in a prospective large cohort of HCV patients with long follow‐up. This was a prospective observational cohort study including 2372 CHC patients with advanced liver fibrosis or cirrhosis receiving DAA therapy in outpatient clinics at the Egyptian Liver Research Institute and Hospital since January 2015. Liver fibrosis was assessed using transient elastography. Abdominal ultrasonography and AFP measurement were done at baseline and follow‐up visits every 6 months, in addition to triphasic abdominal MSCT when needed. Patients were followed up after achieving SVR12 for at least 12 months. HCC developed in 109 cases during the follow‐up period (mean 23.60 ± 8.25 months). Overall HCC incidence was 2.338/100 PY, 95% CI = 1.942‐2.814. In patients with cirrhosis, the incidence of HCC was 2.917/100 PY, 95% CI = 2.407‐3.535, while in patients with advanced liver fibrosis the incidence of HCC was 0.664/100 PY, 95% CI = 0.333‐1.326. In conclusion, the incidence of HCC was reduced in chronic hepatitis C genotype 4 patients with liver cirrhosis (F4) and advanced hepatic fibrosis (F3) who achieved SVR following DAA therapy.