BACKGROUND: Skin alterations are among the most prominent signs of aging, and they arise from both intrinsic and extrinsic factors that interact and mutually influence one another. The use of D-galactose as an aging model in animals has been widely employed in anti-aging research. Adipose tissue-derived mesenchymal stem cells (Ad-MSCs) are particularly promising for skin anti-aging therapy due to their capacity for effective re-epithelization and secretion of various growth factors essential for skin regeneration. Accordingly, we aimed to examine the potential utility of Ad-MSCs as a therapy for skin anti-aging. METHODS: In this study, we isolated and characterized adipose-derived mesenchymal stem cells (Ad-MSCs) from the epididymal fat of male Sprague Dawley rats. We assessed the in vitro differentiation of Ad-MSCs into epidermal progenitor cells (EPCs) using ascorbic acid and hydrocoritsone. Additionally, we induced skin aging in female Sprague Dawley rats via daily intradermal injection of D-galactose over a period of 8 weeks. Then we evaluated the therapeutic potential of intradermal transplantation of Ad-MSCs and conditioned media (CM) derived from differentiated EPCs in the D-galactose-induced aging rats. Morphological assessments, antioxidant assays, and histopathological examinations were performed to investigate the effects of the treatments. RESULTS: Our findings revealed the significant capability of Ad-MSCs to differentiate into EPCs. Notably, compared to the group that received CM treatment, the Ad-MSCs-treated group exhibited a marked improvement in morphological appearance, antioxidant levels and histological features. CONCLUSIONS These results underscore the effectiveness of Ad-MSCs in restoring skin aging as a potential therapy for skin aging.

OBJECTIVE: To determine whether resveratrol (Res) can correct osteoporosis induced in a rat model of male hypogonadism. METHODS: Thirty-two rats were randomly divided into 4 groups, 8 in each group; 1) a control sham group: underwent a similar surgical procedure for induction of orchiectomy (ORCD) without ligation of any arteries or veins or removal of the testis and epididymis; 2) a control + Res-treated group (Con+Res): underwent sham surgery similar to the control, but was then treated with Res, as described below; 3) an ORCD-induced group: bilateral ORCD surgery as described above, and 4) a ORCD+Res-treated group: bilateral ORCD surgery followed by Res treatment. Res treatment began 4 weeks after ORCD and continued for 12 weeks. After 12 weeks, bone mineral density (BMD) and bone mineral content (BMC) were measured in the tibia and femur of each rat's right hind leg. Blood levels of bone turnover indicators such as deoxypyridinoline (Dpd), N-telopeptide of type I collagen (NTX I), alkaline phosphatase (ALP), and osteocalcin (OC), as well as receptor activator of nuclear factor kappa B (RANK) and osteoprotegerin (OPG) were assessed. RESULTS: ORCD significantly decreased BMD (P<0.01) and significantly increased bone resorption, manifested by increased RANK. In addition, it inhibited serum levels of OPG and OC. Res treatment after ORCD effectively increased serum levels of bone formation markers such as OPG and OC, compared with testisectomized rats (P<0.05). CONCLUSION Res could ameliorate bone loss induced by male hypogonadism, possible via restoration of the normal balance between RANK and OPG.
Rats ; Male ; Animals ; Bone Density ; Resveratrol/pharmacology* ; Osteoporosis ; Osteoprotegerin/pharmacology* ; Bone Remodeling ; Hypogonadism ; RANK Ligand/pharmacology*

Background: Current therapies are quite unsuccessful in the management of neuropathic pain. Therefore, considering the inhibitory characteristics of GABA mediators, the present systematic review and meta-analysis aimed to determine the efficacy of GABAergic neural precursor cells on neuropathic pain management. Methods: Search was conducted on Medline, Embase, Scopus, and Web of Science databases. A search strategy was designed based on the keywords related to GABAergic cells combined with neuropathic pain. The outcomes were allodynia and hyperalgesia. The results were reported as a pooled standardized mean difference (SMD) with a 95% confidence interval (95% CI). Results: Data of 13 studies were analyzed in the present meta-analysis. The results showed that administration of GABAergic cells improved allodynia (SMD = 1.79;95% CI: 0.87, 271; P < 0.001) and hyperalgesia (SMD = 1.29; 95% CI: 0.26, 2.32; P = 0.019). Moreover, the analyses demonstrated that the efficacy of GABAergic cells in the management of allodynia and hyperalgesia is only observed in rats. Also, only genetically modified cells are effective in improving both of allodynia, and hyperalgesia. Conclusions A moderate level of pre-clinical evidence showed that transplantation of genetically-modified GABAergic cells is effective in the management of neuropathic pain. However, it seems that the transplantation efficacy of these cells is only statistically significant in improving pain symptoms in rats. Hence, caution should be exercised regarding the generalizability and the translation of the findings from rats and mice studies to large animal studies and clinical trials.

Background: The thoracic retrolaminar block (TRLB) is a relatively new regional analgesia technique that can be used as an alternative to the thoracic paravertebral block. This study aimed to evaluate the postoperative analgesia effects of ultrasound-guided TRLB in children undergoing open cardiac surgery via median sternotomy incision. Methods: Sixty-six patients aged 2–8 years were recruited. In the TRLB group, 0.25% bupivacaine 0.4 ml/kg was injected into the retrolaminar space on both sides at the level of the T4 lamina. Patients in the control group were injected with 0.9% saline. The primary outcome measure was fentanyl consumption in the first 24 h post-extubation. The secondary outcome measures were the total intraoperative fentanyl consumption, postoperative modified objective pain score (MOPS), and time to extubation. Results: The total intraoperative fentanyl requirements and fentanyl consumption in the first 24 h post-extubation were significantly lower (P < 0.001) in the TRLB group (9.3 ± 1.2; 6.9 ± 2.1 μg/kg, respectively) than in the control group (12.5 ± 1.4; 16.6 ± 2.8, respectively). The median (Q1, Q3) time to extubation was significantly shorter (P < 0.001) in the TRLB group (2 [1, 3] h) than in the control group (6 [4.5, 6] h). The MOPS was significantly lower (P < 0.05) in the TRLB group than in the control group at 0, 2, 4, 8, 12 and 16 h post-extubation. Conclusions Bilateral ultrasound-guided TRLB is effective in providing postoperative analgesia in children undergoing open cardiac surgery via median sternotomy incision.

Background: and Purpose Recent studies suggested an increased incidence of cerebral venous thrombosis (CVT) during the coronavirus disease 2019 (COVID-19) pandemic. We evaluated the volume of CVT hospitalization and in-hospital mortality during the 1st year of the COVID-19 pandemic compared to the preceding year. Methods: We conducted a cross-sectional retrospective study of 171 stroke centers from 49 countries. We recorded COVID-19 admission volumes, CVT hospitalization, and CVT in-hospital mortality from January 1, 2019, to May 31, 2021. CVT diagnoses were identified by International Classification of Disease-10 (ICD-10) codes or stroke databases. We additionally sought to compare the same metrics in the first 5 months of 2021 compared to the corresponding months in 2019 and 2020 (ClinicalTrials.gov Identifier: NCT04934020). Results: There were 2,313 CVT admissions across the 1-year pre-pandemic (2019) and pandemic year (2020); no differences in CVT volume or CVT mortality were observed. During the first 5 months of 2021, there was an increase in CVT volumes compared to 2019 (27.5%; 95% confidence interval [CI], 24.2 to 32.0; P<0.0001) and 2020 (41.4%; 95% CI, 37.0 to 46.0; P<0.0001). A COVID-19 diagnosis was present in 7.6% (132/1,738) of CVT hospitalizations. CVT was present in 0.04% (103/292,080) of COVID-19 hospitalizations. During the first pandemic year, CVT mortality was higher in patients who were COVID positive compared to COVID negative patients (8/53 [15.0%] vs. 41/910 [4.5%], P=0.004). There was an increase in CVT mortality during the first 5 months of pandemic years 2020 and 2021 compared to the first 5 months of the pre-pandemic year 2019 (2019 vs. 2020: 2.26% vs. 4.74%, P=0.05; 2019 vs. 2021: 2.26% vs. 4.99%, P=0.03). In the first 5 months of 2021, there were 26 cases of vaccine-induced immune thrombotic thrombocytopenia (VITT), resulting in six deaths. Conclusions During the 1st year of the COVID-19 pandemic, CVT hospitalization volume and CVT in-hospital mortality did not change compared to the prior year. COVID-19 diagnosis was associated with higher CVT in-hospital mortality. During the first 5 months of 2021, there was an increase in CVT hospitalization volume and increase in CVT-related mortality, partially attributable to VITT.

Objective: This study aimed to characterize a validated model for predicting oocyte retrieval in controlled ovarian stimulation (COS) and to construct model-based nomograms for assistance in clinical decision-making regarding the gonadotropin protocol and dose. Methods: This observational, retrospective, cohort study included 636 women with primary unexplained infertility and a normal menstrual cycle who were attempting assisted reproductive therapy for the first time. The enrolled women were split into an index group (n=497) for model building and a validation group (n=139). The primary outcome was absolute oocyte count. The dose-response relationship was tested using modified Poisson, negative binomial, hybrid Poisson-Emax, and linear models. The validation group was similarly analyzed, and its results were compared to that of the index group. Results: The Poisson model with the log-link function demonstrated superior predictive performance and precision (Akaike information criterion, 2,704; λ=8.27; relative standard error (λ)=2.02%). The covariate analysis included women’s age (p<0.001), antral follicle count (p<0.001), basal follicle-stimulating hormone level (p<0.001), gonadotropin dose (p=0.042), and protocol type (p=0.002 and p<0.001 for short and antagonist protocols, respectively). The estimates from 500 bootstrap samples were close to those of the original model. The validation group (n=139) showed model assessment metrics comparable to the index model. Based on the fitted model, a static nomogram was built to improve visualization. In addition, a dynamic electronic tool was created for convenience of use. Conclusion Based on our validated model, nomograms were constructed to help clinicians individualize the stimulation protocol and gonadotropin doses in COS cycles.

Objective: This study aimed to characterize a validated model for predicting oocyte retrieval in controlled ovarian stimulation (COS) and to construct model-based nomograms for assistance in clinical decision-making regarding the gonadotropin protocol and dose. Methods: This observational, retrospective, cohort study included 636 women with primary unexplained infertility and a normal menstrual cycle who were attempting assisted reproductive therapy for the first time. The enrolled women were split into an index group (n=497) for model building and a validation group (n=139). The primary outcome was absolute oocyte count. The dose-response relationship was tested using modified Poisson, negative binomial, hybrid Poisson-Emax, and linear models. The validation group was similarly analyzed, and its results were compared to that of the index group. Results: The Poisson model with the log-link function demonstrated superior predictive performance and precision (Akaike information criterion, 2,704; λ=8.27; relative standard error (λ)=2.02%). The covariate analysis included women’s age (p<0.001), antral follicle count (p<0.001), basal follicle-stimulating hormone level (p<0.001), gonadotropin dose (p=0.042), and protocol type (p=0.002 and p<0.001 for short and antagonist protocols, respectively). The estimates from 500 bootstrap samples were close to those of the original model. The validation group (n=139) showed model assessment metrics comparable to the index model. Based on the fitted model, a static nomogram was built to improve visualization. In addition, a dynamic electronic tool was created for convenience of use. Conclusion Based on our validated model, nomograms were constructed to help clinicians individualize the stimulation protocol and gonadotropin doses in COS cycles.

OBJECTIVE: Few studies have prospectively evaluated the diagnostic accuracy and temporal impact of ultrasound in the emergency department (ED) in a randomized manner. In this study, we aimed to perform a randomized, standard therapy controlled evaluation of the diagnostic accuracy and temporal impact of a standardized ultrasound strategy, versus standard care, in patients presenting to the ED with acute dyspnea.METHODS: The patients underwent a standardized ultrasound examination that was blinded to the team caring for the patient. Ultrasound results remained blinded in patients randomized to the treating team but were unblinded in the interventional cohort. Scans were performed by trained emergency physicians. The gold standard diagnosis (GSDx) was determined by two physicians blinded to the ultrasound results. The same two physicians reviewed all data >30 days after the index visit.RESULTS: Fifty-nine randomized patients were enrolled. The mean±standard deviation age was 54.4±11 years, and 37 (62%) were male. The most common GSDx was acute heart failure with reduced ejection fraction in 13 (28.3%) patients and airway diseases such as acute exacerbation of asthma or chronic obstructive pulmonary disease in 10 (21.7%). ED diagnostic accuracy, as compared to the GSDx, was 76% in the ultrasound cohort and 79% in the standard care cohort (P=0.796). Compared with the standard care cohort, the final diagnosis was obtained much faster in the ultrasound cohort (mean±standard deviation: 12±3.2 minutes vs. 270 minutes, P<0.001).CONCLUSION: A standardized ultrasound approach is equally accurate, but enables faster ED diagnosis of acute dyspnea than standard care.
Asthma ; Cohort Studies ; Diagnosis ; Diagnostic Imaging ; Dyspnea ; Emergencies ; Emergency Service, Hospital ; Heart Failure ; Humans ; Male ; Prospective Studies ; Pulmonary Disease, Chronic Obstructive ; Ultrasonography

OBJECTIVES: This paper presents a systematic review and meta-analysis of the effect of preheating on the hardness of nanofilled, nanoceramic, nanohybrid, and microhybrid resin composites. MATERIALS AND METHODS: An electronic search of papers on MEDLINE/PubMed, ScienceDirect, and EBSCOhost was performed. Only in vitro studies were included. Non-English studies, case reports, clinical trials, and review articles were excluded. A meta-analysis of the reviewed studies was conducted to quantify differences in the microhardness of the Z250 microhybrid resin composite using the Comprehensive Meta-Analysis software. RESULTS: Only 13 studies met the inclusion criteria for this systematic review. The meta-analysis showed that there were significant differences between the non-preheated and preheated modes for both the top and bottom surfaces of the specimens (p < 0.05). The microhardness of the Z250 resin composite on the top surface in the preheated mode (78.1 ± 2.9) was higher than in the non-preheated mode (67.4 ± 4.0; p < 0.001). Moreover, the microhardness of the Z250 resin composite on the bottom surface in the preheated mode (71.8 ± 3.8) was higher than in the non-preheated mode (57.5 ± 5.7, p < 0.001). CONCLUSIONS: Although the results reported in the reviewed studies showed great variability, sufficient scientific evidence was found to support the hypothesis that preheating can improve the hardness of resin composites.
Hardness ; In Vitro Techniques

Objective: To isolate and identify the polyphenolic constituents of Dypsis lutescens, and evaluate the hepatoprotective activity of the ethanolic extract of Dypsis lutescens leaves. Methods: Hepatoprotective, antioxidant and anti-inflammatory effects of two doses of Dypsis lutescens ethanolic leaf extract were investigated in five groups of six rats each administered with the ethanolic extract of Dypsis lutescens leaves. Liver function parameters were assessed, histopathological study was carried out, the anti-inflammatory mediators and the antioxidant potential in the liver tissues were evaluated. In addition, the total ethanolic extract of Dypsis lutescens leaves was subjected to different chromatographic separation techniques to yield ten phenolic compounds. The isolated compounds structures were spectroscopically elucidated. Results: Hepatoprotective activity of Dypsis lutescens ethanolic extract was estimated for the first time and showed significant activity against histopathological changes induced by D-galactosamine in liver. The extract improved the liver functions. Compared to the D-galactosamine group, the architecture of the liver in the treated groups was improved in the histopathological examination. These results proved the hepatoprotective activity of Dypsis lutescens and its ability in attenuating liver oxidative damage and inflammation. Phytochemical investigations of the total extract afforded ten compounds from the genus Dypsis. Conclusions: The alcoholic extract of Dypsis lutescens exerted potential hepatoprotective action, maintaining liver health and functions.