Biodegradation of an injectable treated dentin matrix hydrogel as a novel pulp capping agent for dentin regeneration.

BACKGROUND: A novel injectable mixture termed treated dentin matrix hydrogel (TDMH) has been introduced for restoring dentin defect in DPC. However, no study evaluated its physiological biodegradation. Therefore, the present study aimed to assess scaffold homogeneity, mechanical properties and biodegradability in vitro and in vivo and the regenerated dentin induced by TDMH as a novel pulp capping agent in human permanent teeth. METHODS: Three TDMH discs were weighted, and dry/wet ratios were calculated in four slices from each disc to evaluate homogeneity. Hydrogel discs were also analyzed in triplicate to measure the compressive strength using a universal testing machine. The in vitro degradation behavior of hydrogel in PBS at 37 °C for 2 months was also investigated by monitoring the percent weight change. Moreover, 20 intact fully erupted premolars were included for assessment of TDMH in vivo biodegradation when used as a novel injectable pulp capping agent. The capped teeth were divided into four equal groups according to extraction interval after 2-, 8-, 12- and 16-weeks, stained with hematoxylin-eosin for histological and histomorphometric evaluation. Statistical analysis was performed using F test (ANOVA) and post hoc test (p = 0.05). RESULTS: No statistical differences among hydrogel slices were detected with (p = 0.192) according to homogeneity. TDMH compression modulus was (30.45 ± 1.11 kPa). Hydrogel retained its shape well up to 4 weeks and after 8 weeks completely degraded. Histological analysis after 16 weeks showed a significant reduction in TDMH area and a simultaneous significant increase in the new dentin area. The mean values of TDMH were 58.8% ± 5.9 and 9.8% ± 3.3 at 2 and 16 weeks, while the new dentin occupied 9.5% ± 2.8 at 2 weeks and 82.9% ± 3.8 at 16 weeks. CONCLUSIONS: TDMH was homogenous and exhibited significant stability and almost completely recovered after excessive compression. TDMH generally maintained their bulk geometry throughout 7 weeks. The in vivo response to TDMH was characterized by extensive degradation of the hydrogel and dentin matrix particles and abundant formation of new dentin. The degradation rate of TDMH matched the rate of new dentin formation. TRIAL REGISTRATION: PACTR201901866476410: 30/1/2019.

Past and Future Perspectives for Hepatitis B and C in Pakistan.

Background Hepatitis B and C are viral infections of the liver transmitted by blood contamination. These infections are endemic in Pakistan and put a tremendous burden on its healthcare system. We conducted this study to assess the prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections in Gujranwala, Pakistan, from 2010 to 2015 and determine the trend of future infections for a prediction of the disease burden by 2030 so policymakers can make informed decisions. Methods We conducted a retrospective cross-sectional study of 66,308 healthy blood donor samples at District Headquarters Teaching Hospital in Gujranwala from January 2010 to December 2015. Samples were screened for HBV and HCV using the kit method, and data were analyzed using IBM SPSS Statistics for Windows, version 20.0 (IBM Corp., Armonk, NY). We applied a least squares regression to our results to predict HBV and HCV incidence in 2030. Results A total of 715 samples (1.08%) were positive for HBV and 1,846 samples (2.78%) were positive for HCV. Our projections indicate that 3.25% of patients in Pakistan will be positive for HBV, and 6.36% will be positive for HBC by 2030. Conclusion We found an unexpectedly greater burden of HBV and HCV in the recent past than at current levels. The predicted percentages of future burden over the next decade were alarmingly high. These data necessitate implementing preventive and therapeutic measures by policymakers to reduce the disease burden and mortality in Pakistan.

Solving text clustering problem using a memetic differential evolution algorithm.

The text clustering is considered as one of the most effective text document analysis methods, which is applied to cluster documents as a consequence of the expanded big data and online information. Based on the review of the related work of the text clustering algorithms, these algorithms achieved reasonable clustering results for some datasets, while they failed on a wide variety of benchmark datasets. Furthermore, the performance of these algorithms was not robust due to the inefficient balance between the exploitation and exploration capabilities of the clustering algorithm. Accordingly, this research proposes a Memetic Differential Evolution algorithm (MDETC) to solve the text clustering problem, which aims to address the effect of the hybridization between the differential evolution (DE) mutation strategy with the memetic algorithm (MA). This hybridization intends to enhance the quality of text clustering and improve the exploitation and exploration capabilities of the algorithm. Our experimental results based on six standard text clustering benchmark datasets (i.e. the Laboratory of Computational Intelligence (LABIC)) have shown that the MDETC algorithm outperformed other compared clustering algorithms based on AUC metric, F-measure, and the statistical analysis. Furthermore, the MDETC is compared with the state of art text clustering algorithms and obtained almost the best results for the standard benchmark datasets.

An improved adaptive memetic differential evolution optimization algorithms for data clustering problems.

The performance of data clustering algorithms is mainly dependent on their ability to balance between the exploration and exploitation of the search process. Although some data clustering algorithms have achieved reasonable quality solutions for some datasets, their performance across real-life datasets could be improved. This paper proposes an adaptive memetic differential evolution optimisation algorithm (AMADE) for addressing data clustering problems. The memetic algorithm (MA) employs an adaptive differential evolution (DE) mutation strategy, which can offer superior mutation performance across many combinatorial and continuous problem domains. By hybridising an adaptive DE mutation operator with the MA, we propose that it can lead to faster convergence and better balance the exploration and exploitation of the search. We would also expect that the performance of AMADE to be better than MA and DE if executed separately. Our experimental results, based on several real-life benchmark datasets, shows that AMADE outperformed other compared clustering algorithms when compared using statistical analysis. We conclude that the hybridisation of MA and the adaptive DE is a suitable approach for addressing data clustering problems and can improve the balance between global exploration and local exploitation of the optimisation algorithm.

Identification and electrophysiological characterization of early left atrial structural remodeling as a predictor for atrial fibrillation recurrence after pulmonary vein isolation.

BACKGROUND: Voltage-guided substrate ablation following pulmonary vein isolation (PVI) improves atrial fibrillation (AF) ablation outcomes. However, by setting an upper voltage cutoff of 0.5 mV during sinus rhythm (SR) to guided substrate ablation using electroanatomic voltage mapping (EAVM), mildly affected low-voltage area (maLVA) may be undetected. We sought to determine the optimal bipolar voltage cutoff to identify maLVA, its electrogram complexity, and the implication on ablation outcome. METHODS AND RESULTS: Left atrial (LA) EAVMs were obtained in patients without AF and structural heart disease (control) to devise a voltage cutoff to identify maLVA. Subsequently, we investigated 100 patients without low-voltage area (LVA) of < 0.5 mV who underwent PVI alone. In our 6 control cohorts, 95% of LA regional bipolar voltage was > 1.17 mV. maLVA, defined as <1.1 mV, was present in 43% of AF patients, associated with higher prevalence of abnormal electrograms (44.1% vs. 4.4%, P < 0.001). During a median of 2.4 years, patients with maLVA had higher recurrence rate (Log-rank P < 0.001), and maLVA was an independent predictor for recurrence in a multivariate analysis (hazard ratio [HR] 3.944; 95% confidence interval [CI] 1.292-12.042; P = 0.016). CONCLUSIONS: A control-derived LA voltage cutoff of <1.1 mV for EAVM in SR reveals maLVA, harboring abnormal electrograms, as an independent predictor for recurrences after PVI alone in patients without LVA (< 0.5 mV). Adjunctive maLVA-guided substrate ablation targeting mildly remodeled and potentially arrhythmogenic LA substrate may further improve the long-term outcome of AF ablation.

Gender differences control the susceptibility to ER stress-induced acute kidney injury.

Endoplasmic reticulum (ER) stress contributes to acute kidney injury induced by several causes. Kidney dysfunction was shown to be influenced by gender differences. In this study we observed differences in the severity of kidney injury between male and female mice in response to tunicamycin, an ER stress agent. Tunicamycin-treated male mice showed a severe decline in kidney function and extensive kidney damage of proximal tubules in the kidney outer cortex (S1 and S2 segments). Interestingly, female tunicamycin-treated mice did not show a decline in kidney function, and their kidneys showed damage localized primarily to proximal tubules in the inner cortex (S3 segment). Protein markers of ER stress, glucose-regulated protein, and X-box binding protein 1 were also more elevated in male mice. Similarly, the induction of apoptosis was higher in tunicamycin-treated male mice, as measured by the activation of Bax and caspase-3. Testosterone administered to female mice before tunicamycin resulted in a phenotype similar to male mice with a comparable decline in renal function, tissue morphology, and induction of ER stress markers. We conclude that kidneys of male mice are much more susceptible to ER stress-induced acute kidney injury than those of females. Moreover, this sexual dimorphism could provide an interesting model to study the relation between kidney function and injury to a specific nephron segment.

Altered systemic hemodynamic and baroreflex response to angiotensin II in postural tachycardia syndrome.

BACKGROUND: Postural tachycardia syndrome (POTS) is characterized by excessive orthostatic tachycardia and significant functional disability. We have previously found that patients with POTS have increases in plasma angiotensin II (Ang II) that are twice as high as healthy subjects despite normal blood pressures (BPs). In this study, we assess systemic and renal hemodynamic and functional responses to Ang II infusion in patients with POTS compared with healthy controls. METHODS AND RESULTS: Following a 3-day sodium-controlled diet, we infused Ang II (3 ng/kg per minute) for 1 hour in patients with POTS (n=15) and healthy controls (n=13) in the supine position. All study subjects were women with normal BP. Ages were similar for patients with POTS and controls (mean±SEM, 30±2 versus 26±1 years; P=0.11). We measured the changes from baseline mean arterial pressure, renal plasma flow, plasma renin activity, aldosterone, urine sodium, and baroreflex sensitivity in both groups. In response to Ang II infusion, patients with POTS had a blunted increase compared with controls in mean arterial pressure (10±1 versus 14±1 mm Hg, P=0.01) and diastolic BP (9±1 versus 13±1 mm Hg, P=0.01) but not systolic BP (13±2 versus 15±2 mm Hg, P=0.40). Renal plasma flow decreased similarly with Ang II infusion in patients with POTS versus controls (-166±20 versus -181±17 mL/min per 1.73 kg/m(2), P=0.58). Postinfusion, the decrease in plasma renin activity (-0.9±0.2 versus -0.6±0.2 ng/mL per hour, P=0.43) and the increase in aldosterone (17±1 versus 15±2 pg/mL, P=0.34) were similar in both groups. The decrease in urine sodium excretion was similar in patients with POTS and controls (-49±12 versus -60±16 mEq/g creatinine, P=0.55). The spontaneous baroreflex sensitivity at baseline was significantly lower in patients with POTS compared with controls (10.1±1.2 versus 16.8±1.5 ms/mm Hg, P=0.003), and it was further reduced with Ang II infusion. CONCLUSIONS: Patients with POTS have blunted vasopressor response to Ang II and impaired baroreflex function. This impaired vasoconstrictive response might be exaggerated with upright posture and may contribute to the subsequent orthostatic tachycardia that is the hallmark of this disorder. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00962949.

Dysautonomia: perioperative implications.

Severe autonomic failure occurs in approximately 1 in 1,000 people. Such patients are remarkable for the striking and sometimes paradoxic responses they manifest to a variety of physiologic and pharmacologic stimuli. Orthostatic hypotension is often the finding most commonly noted by physicians, but a myriad of additional and less understood findings also occur. These findings include supine hypertension, altered drug sensitivity, hyperresponsiveness of blood pressure to hypo/hyperventilation, sleep apnea, and other neurologic disturbances. In this article the authors will review the clinical pathophysiology that underlies autonomic failure, with a particular emphasis on those aspects most relevant to the care of such patients in the perioperative setting. Strategies used by clinicians in diagnosis and treatment of these patients, and the effect of these interventions on the preoperative, intraoperative, and postoperative care that these patients undergo is a crucial element in the optimized management of care in these patients.

Abnormalities of angiotensin regulation in postural tachycardia syndrome.

BACKGROUND: Postural tachycardia syndrome (POTS) is a disorder characterized by excessive orthostatic tachycardia and significant functional disability. We previously reported that POTS patients have low blood volume and inappropriately low plasma renin activity (PRA) and aldosterone. In this study, we sought to more fully characterize the renin-angiotensin-aldosterone system (RAAS) to gain a better understanding of the pathophysiology of POTS. OBJECTIVE: The purpose of this study was to prospectively assess the plasma levels of angiotensin (Ang) peptides and their relationship to other RAAS components in patients with POTS compared with healthy controls. METHODS: Heart rate, PRA, Ang I, Ang II, Ang (1-7), and aldosterone were measured in POTS patients (n = 38) and healthy controls (n = 13) while they were consuming a sodium-controlled diet. RESULTS: POTS patients had larger orthostatic increases in heart rate than did controls (52 ± 3 [mean ± SEM] bpm vs 27 ± 6 bpm, P = .001). Plasma Ang II was significantly higher in POTS patients (43 ± 3 pg/mL vs 28 ± 3 pg/mL, P = .006), whereas plasma Ang I and angiotensin 1-7 [Ang-(1-7)] were similar between groups. Despite the twofold increase of Ang II, POTS patients trended to lower PRA levels than did controls (0.9 ± 0.1 ng/mL/h vs 1.6 ± 0.5 ng/mL/h, P = .268) and lower aldosterone levels (4.6 ± 0.8 pg/mL vs 10.0 ± 3.0 pg/mL, P = .111). Estimated angiotensin-converting enzyme-2 (ACE2) activity was significantly lower in POTS patients than in controls (0.25 ± 0.02 vs 0.33 ± 0.03, P = .038). CONCLUSION: Some patients with POTS have inappropriately high plasma Ang II levels, with low estimated ACE2 activity. We propose that these abnormalities in Ang regulation may play a key role in the pathophysiology of POTS in some patients.