Fabrication and characterization of a novel injectable human amniotic membrane hydrogel for dentin-pulp complex regeneration.

OBJECTIVE: Injectable biomaterials that can completely fill the root canals and provide an appropriate environment will have potential application for pulp regeneration in endodontics. This study aimed to fabricate and characterize a novel injectable human amniotic membrane (HAM) hydrogel scaffold crosslinked with genipin, enabling the proliferation of Dental Pulp Stem Cells (DPSCs) and optimizing pulp regeneration. METHODS: HAM extracellular matrix (ECM) hydrogels (15, 22.5, and 30 mg/ml) crosslinked with different genipin concentrations (0, 0.1, 0.5, 1, 5, and 10 mM) were evaluated for mechanical properties, tooth discoloration, cell viability, and proliferation of DPSCs. The hydrogels were subcutaneously injected in rats to assess their immunogenicity. The hydrogels were applied in a root canal model and subcutaneously implanted in rats to determine their regenerative potential for eight weeks, and histological and immunostaining analyses were performed. RESULTS: Hydrogels crosslinked with low genipin concentration demonstrated low tooth discoloration, but 0.1 mM genipin crosslinked hydrogels were excluded due to their unfavourable mechanical properties. The degradation ratio was lower in hydrogels crosslinked with 0.5 mM genipin. The 30 mg/ml-0.5 mM crosslinked hydrogel exhibited a microporous structure, and the modulus of elasticity was 1200 PA. In vitro, cell culture showed maximum viability and proliferation in 30 mg/ml-0.5 mM crosslinked hydrogel. All groups elicited minimum immunological responses, and highly vascularized pulp-like tissue was formed in human tooth roots in both groups with/without DPSCs. SIGNIFICANCE: Genipin crosslinking improved the biodegradability of injectable HAM hydrogels and conferred higher biocompatibility. Hydrogels encapsulated with DPSCs can support stem cell viability and proliferation. In addition, highly vascularized pulp-like tissue formation by this biomaterial displayed potential for pulp regeneration.

Human amniotic membrane extracellular matrix scaffold for dental pulp regeneration in vitro and in vivo.

AIM: In order to obtain a 3-dimentional scaffold with predictable clinical results for pulp regeneration, this study aims to fabricate and characterize a porous decellularized human amniotic membrane (HAM) extracellular matrix (ECM) scaffold, and evaluate its potential to promote pulp regeneration in vitro and in vivo. METHODOLOGY: The HAM was decellularized, and its histology and DNA content were analysed to confirm decellularization. The scaffolds were synthesized with 15, 22.5 and 30 mg/ml concentrations. The porosity, pore size, phosphate-buffered saline (PBS) absorption and degradation rate of the scaffolds were assessed. In vitro experiments were performed on human dental pulp stem cells (hDPSCs) to assess their viability, proliferation, adhesion and migration on the scaffolds. The optimal group was selected for in vivo immunogenicity assessment and was also used as the cell-free or cell-loaded scaffold in root segment models to evaluate pulp regeneration. All nonparametric data were analysed with the Kruskal-Wallis test followed by Dunn's post hoc test, whilst quantitative data were analysed with one-way anova. RESULTS: Decellularization of HAM was confirmed (p < .05). The porosity of all scaffolds was more than 95%, and the pore size decreased with an increase in ECM concentration (p < .01). PBS absorption was not significantly different amongst the groups, whilst 30 mg/ml ECM scaffold had the highest degradation rate (p < .01). The hDPSCs adhered to the scaffold, whilst their proliferation rate increased over time in all groups (p < .001). Cell migration was higher in 30 mg/ml ECM scaffold (p < .05). In vivo investigation with 30 mg/ml ECM scaffold revealed mild to moderate inflammatory response. In root segments, both cell-free and cell-loaded 30 mg/ml scaffolds were replaced with newly formed, pulp-like tissue with no significant difference between groups. Immunohistochemical assessments revealed high revascularization and collagen content with no significant difference amongst the groups. CONCLUSION: The 30 mg/ml HAM ECM scaffold had optimal physical properties and better supported hDPSC migration. The HAM ECM scaffold did not interfere with formation of pulp-like tissue and revascularization within the root canal when employed as both cell-free and cell-loaded scaffold. These results highlight the potential of HAM ECM membrane for further investigations in regenerative endodontics.

The Prevalence of Hypothyroidism among Patients With ß-Thalassemia: A Systematic Review and Meta-Analysis of Cross-Sectional Studies.

As a cause of chronic blood transfusions, iron overload is an important issue in ß-thalassemia (ß-thal) patients that leads to multiple organ dysfunctions. This is an updated meta-analysis conducted to summarize the existing evidence of the prevalence of hypothyroidism (HT) among patients with transfusion-dependent (TDT) and non transfusion-dependent ß-thal (NTDT) and for the first time we meta-analyzed the relationship between ferritin level and HT. This systematic review and meta-analysis were done according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. We searched databases including Web of Science (ISI), Scopus, PubMed, Embase, and Scholar. The quality of the included studies was assessed based on the Newcastle-Ottawa scale (NOS) checklist. Meta-analysis was done using Stata statistical software. The pooled prevalence of total HT, subclinical HT, and overt HT among ß-thal patients was 13.25 [95% confidence interval (95% CI): 10.29-16.21; 11.84, 95% CI: 8.43-15.25 and 12.46, 95% CI: 1.05-23.87], respectively. The prevalence of total HT was 16.22% (95% CI: 12.36-20.08) in TDT and 7.22% (95% CI: 3.66-10.78) in NTDT patients. Serum ferritin (SF) levels were significantly lower in euthyroid compared to hypothyroid patients [standard mean difference (SMD) -2.15 (95% CI: -3.08, -1.21, p value <0.001]. The prevalence of HT was higher in TDT compared to NTDT patients. Moreover, our results showed a significant association of high serum ferritin (SF) levels with hypothyroidism in ß-thal patients. Both of these findings highlight the importance of prevention measures and timely diagnosis and management of iron overload in ß-thal patients.

The effect of a short-term physical activity after meals on gastrointestinal symptoms in individuals with functional abdominal bloating: a randomized clinical trial.

AIM: The present study aims to compare the effect of a short duration postprandial walking and prokinetic medications on bloating reported by healthy individuals. BACKGROUND: Abdominal bloating imposes significant clinical, social and economic burden on the healthcare systems; however, treatment of bloating is limited and not effective in all individuals with this symptom. Prokinetic agents are recommended in the treatment of bloating in individuals without underlying disorders traditionally. METHODS: The study participants were randomized into two groups of control and intervention. In the control group, individuals were given daily domperidone plus activated dimethicone as a prokinetic medication, while the subjects in the intervention group were asked to perform a 10-15-minutewalk after each meal. The study duration was 4 weeks, the subjects were re-visited afterwards, and their symptoms was compared before and after the study. RESULTS: This study consists of 94 individuals including 24 men and 70 women with mean age of 44.47±12.25 years with 49 participants in the control group and 45 participants in the intervention group. Both prokinetic medication use and minimal exercise after meals were associated with significant improvements in the GI tract symptoms such as belching, flatus, postprandial epigastric fullness/ bloating, gas incontinency and abdominal discomfort/pain (p-value <0.001). The changes in the score of the gastrointestinal symptoms from beginning to end of study between the two arms of study were not statistically significant except for postprandial epigastric fullness/ bloating symptoms where the intervention was superior to the use of prokinetics (p-value=0.002). CONCLUSION: This study shows that physical activity could be effective in relieving abdominal bloating symptoms. In contrast to other means of treatment proposed for abdominal bloating and its related symptoms, it needs no materials or equipment and can be easily performed by any individual.

Hematologic autoimmune disorders in the course of COVID-19: a systematic review of reported cases.

OBJECTIVE: As COVID-19 is a new emerging disease, the hematological/immunological changes that develop in the infected patients remain unknown. This study aims to systematically review the hematologic autoimmune complications in these patients. METHOD: Data from three online databases including Medline (via PubMed), Scopus and Web of Science were searched on 19 December 2020, and after excluding duplicate, irrelevant and inappropriate records, eligible documents were identified. Afterwards, information such as patients' history, presentations, paraclinical data, treatment course and outcome were extracted from the records. RESULTS: A total of 58 documents were considered to be eligible for data extraction which described 94 patients with COVID-19 who developed hematologic autoimmune disorder in their course of infection. Of these patients with COVID-19, the most common hematologic autoimmune disorder was immune thrombocytopenic purpura (55 cases) followed by autoimmune hemolytic anemia (22 cases). Other hematologic autoimmune disorders include antiphospholipid syndrome, thrombotic thrombocytopenic purpura, Evans syndrome and autoimmune neutropenia. CONCLUSION: The current study would help us to always consider an autoimmune etiology for cases with abnormal hematologic finding which further lead to an appropriate treatment of the patients, especially when the symptoms present in about 1-2 weeks after the first manifestation of the infection symptoms. Maybe, at least in this pandemic, it should be recommended to evaluate patients with unexpected and unexplained decrease in their hemoglobulin or platelet count for COVID-19. Another challenging issue is the treatment options. Given the multiorgan involvement and multifaceted nature of the infection, an individualized approach should be taken for each patient.

An Infant with Acute Bloody Diarrhea and Gastrointestinal Basidiobolomycosis: An Unusual Presentation of a Rare Disease.

Basidiobolomycosis is a fungal infection caused mainly by Basidiobolus ranarum, a filamentous fungus of the order Entomophthorales and the family Basidiobolaceae. This infection typically involves the skin and soft tissue; however, visceral organ involvement has also been reported. Here, we report a case of gastrointestinal basidiobolomycosis in a young child who presented with acute bloody diarrhea which was initially misdiagnosed as intussusception.

Percutaneous coronary intervention to treat chronic total occlusion: predictors of technical success and one-year clinical outcome.

We investigated the overall success rate of percutaneous coronary intervention (PCI) as a treatment for coronary chronic total occlusion and sought to determine the predictive factors of technical success and of one-year major adverse cardiac events (MACE). These factors have not been conclusively defined. Using data from our single-center PCI registry, we enrolled 269 consecutive patients (mean age, 56.13 ± 10.72 yr; 66.2% men) who underwent first-time PCI for chronic total occlusion (duration, ≥3 mo) from March 2006 through September 2010. We divided them into 2 groups: procedural success and procedural failure. We compared occurrences of in-hospital sequelae and one-year MACE between the groups, using multivariate models to determine predictors of technical failure and one-year clinical outcome. Successful revascularization was achieved in 221 patients (82.2%). One-year MACE occurred in 13 patients (4.8%), with a predominance of target-vessel revascularization (3.7%). The prevalence of MACE was significantly lower in the procedural-success group (1.8% vs 18.8%; P <0.001). In the multivariate model, technical failure was the only predictor of one-year MACE. The predictors of failed procedures were lesion location, multivessel disease, the occurrence of dissection, a Thrombolysis In Myocardial Infarction flow grade of 0 before PCI, the absence of tapered-stump arterial structure, and an increase in serum creatinine level or lesion length. In our retrospective, observational study, PCI was successful in a high percentage of chronic total occlusion patients and had a low prevalence of complications. This suggests its safety and effectiveness as a therapeutic option.

Mid-Term Follow-Up of Drug-Eluting Stenting for In-Stent Restenosis: Bare-Metal Stents versus Drug-Eluting Stents.

BACKGROUND: Despite major advances in percutaneous coronary intervention (PCI), in-stent restenosis (ISR) remains a therapeutic challenge. We sought to compare the mid-term clinical outcomes after treatment with repeat drug-eluting stent (DES) implantation ("DES sandwich" technique) with DES placement in the bare-metal stent (DES-in-BMS) in a "real world" setting. METHODS: We retrospectively identified and analyzed clinical and angiographic data on 194 patients previously treated with the DES who underwent repeat PCI for ISR with a DES or a BMS. ISR was defined, by visual assessment, as a luminal stenosis greater than 50% within the stent or within 5 mm of its edges. We recorded the occurrence of major adverse cardiac events (MACE), defined as cardiac death, non-fatal myocardial infarction, and the need for target vessel revascularization (TVR). RESULTS: Of the 194 study participants, 130 were men (67.0%) and the mean ± SD of age was 57.0 ± 10.4 years, ranging from 37 to 80 years. In-hospital events (death and Q-wave myocardial infarction) occurred at a similar frequency in both groups. Outcomes at twelve months were also similar between the groups with cumulative clinical MACE at one-year follow-up of 9.6% and 11.3% in the DES-in-BMS and the DES-in-DES groups, respectively (p value = 0.702). Although not significant, there was a trend toward a higher TVR rate in the intra-DES ISR group as compared to the intra-BMS ISR group (0.9% BMS vs. 5.2% DES; p value = 0.16). CONCLUSION: Our study suggests that the outcome of the patients presenting with ISR did not seem to be different between the two groups of DES-in-DES and DES-in-BMS at one-year follow-up, except for a trend toward more frequent TVR in the DES-in-DES group. Repeat DES implantation for DES restenosis could be feasible and safe with a relatively low incidence of MACE at mid-term follow-up.

Opium and risk of laryngeal cancer.

OBJECTIVES/HYPOTHESIS: The study was performed to investigate the possible association between opium dependency and laryngeal cancer. STUDY DESIGN: A hospital-based, group-matched, case-control study was presented. METHODS: Ninety-eight patients with laryngeal cancer and 312 age- and gender-matched control subjects were selected at the otorhinolaryngology ward of a referral university-affiliated hospital. Data on cigarette smoking and alcohol and opium dependency were collected before surgery through semi-structured interview. RESULTS: The crude odds ratios of laryngeal cancer were 15.07 (95% confidence interval [CI], 6.92-32.8 [P <.0001]) for cigarette smoking, 21.55 (95% CI, 10.54-44 [P <.0001]) for opium dependency, and 1.84 (95% CI, 1.008-3.38 [P <.048]) for male gender. Because of strong associations, a logistic regression model was prepared; the odds ratio for gender in the final model was 0.87 (95% CI, 0.39-1.92 [P =.11]). According to the results, it seemed that gender was not an independent risk factor for laryngeal cancer. Also, the adjusted odds ratios for smoking (5.21) (95% CI, 2.33-11.67 [P <.002]) and opium dependency (10.74) (95% CI, 5.76-20.02 [P <.002]) were lower than the crude odds ratios, but both ratios were significant. The mean patient ages were 55.1 years (SD = 12.05 y) in opium-dependent patients and 65.6 years (SD = 12.8 y) in opium-nondependent patients (P =.01). CONCLUSION: The results of the study suggest that opium dependency is not only an independent possible risk factor for laryngeal cancer but also significantly increases the likelihood of developing of the disease at a younger age.