Modulation of the miR-122/Sirt-6/ACE2 axis on experimentally-induced myocardial infarction.

Myocardial infarction (MI) is a progressive myocardial necrosis that can lead to a number of life-threatening complications. MiRNAs have a crucial role in the pathogenesis of many cardiovascular diseases. Remarkably, miR-122 targets the sirtuin-6 (Sirt-6) gene, which is an essential regulator of cardiovascular function and is considered a partial angiotensin converting enzyme 2 (ACE2) activator. Modulation of this axis is supposed to contribute to MI pathogenesis. The current study aims to investigate the cardioprotective effects of xanthenone through targeting the miR-122/Sirt-6/ACE2 axis on experimentally-induced MI in rats. Xanthenone was administered for 14 days and isoprenaline was injected in the last 2 days of the experiment. Xanthenone treatment resulted in a significant downregulation of miR-122, which further upregulated Sirt-6 and thus activated the adenosine monophosphate-activated protein kinase (AMPK). AMPK increases ACE2 levels and results in a decrease in the level of its substrate angiotensin II resulting in the normalization of the inflammatory cytokines and the cardiac biomarkers. Finally, by targeting the miR-122/Sirt-6/AMPK/ACE2 axis, xanthenone has the potential to be a promising cardioprotective agent against MI.

Impact of total marrow/lymphoid irradiation dose to the intestine on graft-versus-host disease in allogeneic hematopoietic stem cell transplantation for hematologic malignancies.

Background and purpose: Graft-versus-host disease (GvHD) is a leading cause of non-relapse mortality in patients undergoing allogeneic hematopoietic stem cell transplantation. The Perugia Bone Marrow Transplantation Unit designed a new conditioning regimen with total marrow/lymphoid irradiation (TMLI) and adaptive immunotherapy. The present study investigated the impact of radiotherapy (RT) doses on the intestine on the incidence of acute GvHD (aGvHD) in transplant recipients, analyzing the main dosimetric parameters. Materials and methods: Between August 2015 and April 2021, 50 patients with hematologic malignancies were enrolled. All patients underwent conditioning with TMLI. Dosimetric parameters (for the whole intestine and its segments) were assessed as risk factors for aGvHD. The RT dose that was received by each intestinal area with aGvHD was extrapolated from the treatment plan for each patient. Doses were compared with those of the whole intestine minus the affected area. Results: Eighteen patients (36%) developed grade ≥2 aGvHD (G2 in 5, G3 in 11, and G4 in 2). Median time to onset was 41 days (range 23-69 days). The skin was involved in 11 patients, the intestine in 16, and the liver in 5. In all 50 TMLI patients, the mean dose to the whole intestine was 7.1 Gy (range 5.07-10.92 Gy). No patient developed chronic GvHD (cGvHD). No dosimetric variable emerged as a significant risk factor for aGvHD. No dosimetric parameter of the intestinal areas with aGvHD was associated with the disease. Conclusion: In our clinical setting and data sample, we have found no clear evidence that current TMLI dosages to the intestine were linked to the development of aGvHD. However, due to some study limitations, this investigation should be considered as a preliminary assessment. Findings need to be confirmed in a larger cohort and in preclinical models.

Total marrow irradiation reduces organ damage and enhances tissue repair with the potential to increase the targeted dose of bone marrow in both young and old mice.

Total body irradiation (TBI) is a commonly used conditioning regimen for hematopoietic stem cell transplant (HCT), but dose heterogeneity and long-term organ toxicity pose significant challenges. Total marrow irradiation (TMI), an evolving radiation conditioning regimen for HCT can overcome the limitations of TBI by delivering the prescribed dose targeted to the bone marrow (BM) while sparing organs at risk. Recently, our group demonstrated that TMI up to 20 Gy in relapsed/refractory AML patients was feasible and efficacious, significantly improving 2-year overall survival compared to the standard treatment. Whether such dose escalation is feasible in elderly patients, and how the organ toxicity profile changes when switching to TMI in patients of all ages are critical questions that need to be addressed. We used our recently developed 3D image-guided preclinical TMI model and evaluated the radiation damage and its repair in key dose-limiting organs in young (~8 weeks) and old (~90 weeks) mice undergoing congenic bone marrow transplant (BMT). Engraftment was similar in both TMI and TBI-treated young and old mice. Dose escalation using TMI (12 to 16 Gy in two fractions) was well tolerated in mice of both age groups (90% survival ~12 Weeks post-BMT). In contrast, TBI at the higher dose of 16 Gy was particularly lethal in younger mice (0% survival ~2 weeks post-BMT) while old mice showed much more tolerance (75% survival ~13 weeks post-BMT) suggesting higher radio-resistance in aged organs. Histopathology confirmed worse acute and chronic organ damage in mice treated with TBI than TMI. As the damage was alleviated, the repair processes were augmented in the TMI-treated mice over TBI as measured by average villus height and a reduced ratio of relative mRNA levels of amphiregulin/epidermal growth factor (areg/egf). These findings suggest that organ sparing using TMI does not limit donor engraftment but significantly reduces normal tissue damage and preserves repair capacity with the potential for dose escalation in elderly patients.

An efficient rectangular optimization method for sparse orthogonal collimator based small animal irradiation.

Objective.Intensity-modulated radiotherapy (IMRT) is widely used in clinical radiotherapy, treating varying malignancies with conformal doses. As the test field for clinical translation, preclinical small animal experiments need to mimic the human radiotherapy condition, including IMRT. However, small animal IMRT is a systematic challenge due to the lack of corresponding hardware and software for miniaturized targets.Approach.The sparse orthogonal collimators (SOC) based on the direct rectangular aperture optimization (RAO) substantially simplified the hardware for miniaturization. This study investigates and evaluates a significantly improved RAO algorithm for complex mouse irradiation using SOC. Because the Kronecker product representation of the rectangular aperture is the main limitation of the computational performance, we reformulated matrix multiplication in the data fidelity term using multiplication with small matrices instead of the Kronecker product of the dose loading matrices. Solving the optimization problem was further accelerated using the Fast Iterative Shrinkage-Thresholding Algorithm (FISTA).Main results.Four mouse cases, including a liver, a brain tumor, a concave U-target, and a complex total marrow irradiation (TMI) case, were included in this study with manually delineated targets and OARs. Seven coplanar-field SOC IMRT (sIMRT) plans were compared with idealistic fluence map based IMRT (iIMRT) plans. For the first three cases with simpler and smaller targets, the differences between sIMRT plans and iIMRT plans in the planning target volumes (PTV) statistics are within 1%. For the TMI case, the sIMRT plans are superior in reducing hot spots (also termedDmax) of PTV, kidneys, lungs, heart, and bowel by 20.5%, 31.5%, 24.67%, 20.13%, and 17.78%, respectively. On average, in four cases in this study, the sIMRT plan conformity is comparable to that of the iIMRT's with lightly increased R50 and Integral Dose by 2.23% and 2.78%.Significance.The significantly improved sIMRT optimization method allows fast plan creation in under 1 min for smaller targets and makes complex TMI planning feasible while achieving comparable dosimetry to idealistic IMRT with fluence map optimization.

Development and characterization of a preclinical total marrow irradiation conditioning-based bone marrow transplant model for sickle cell disease.

Sickle cell disease (SCD) is a serious global health problem, and currently, the only curative option is hematopoietic stem cell transplant (HCT). However, myeloablative total body irradiation (TBI)-based HCT is associated with high mortality/morbidity in SCD patients. Therefore, reduced-intensity (2-4 Gy) total body radiation (TBI) is currently used as a conditioning regimen resulting in mixed chimerism with the rescue of the SCD disease characteristic features. However, donor chimerism gradually reduces in a few years, resulting in a relapse of the SCD features, and organ toxicities remained the primary concern for long-term survivors. Targeted marrow irradiation (TMI) is a novel technique developed to deliver radiation to the desired target while sparing vital organs and is successfully used for HCT in refractory/relapsed patients with leukemia. However, it is unknown if TMI will be an effective treatment for a hematological disorder like SCD without adverse effects seen on TBI. Therefore, we examined preclinical feasibility to determine the tolerated dose escalation, its impact on donor engraftment, and reduction in organ damage using our recently developed TMI in the humanized homozygous Berkley SCD mouse model (SS). We show that dose-escalated TMI (8:2) (8 Gy to the bone marrow and 2 Gy to the rest of the body) is tolerated with reduced organ pathology compared with TBI (4:4)-treated mice. Furthermore, with increased SCD control (AA) mice (25 million) donor BM cells, TMI (8:2)-treated mice show successful long-term engraftment while engraftment failed in TBI (2:2)-treated mice. We further evaluated the benefit of dose-escalated TMI and donor cell engraftment in alleviating SCD features. The donor engraftment in SCD mice completely rescues SCD disease features including recovery in RBCs, hematocrit, platelets, and reduced reticulocytes. Moreover, two-photon microscopy imaging of skull BM of transplanted SCD mice shows reduced vessel density and leakiness compared to untreated control SCD mice, indicating vascular recovery post-BMT.

Feasibility of a Novel Sparse Orthogonal Collimator-Based Preclinical Total Marrow Irradiation for Enhanced Dosimetric Conformality.

Total marrow irradiation (TMI) has significantly improved radiation conditioning for hematopoietic cell transplantation in hematologic diseases by reducing conditioning-induced toxicities and improving survival outcomes in relapsed/refractory patients. Recently, preclinical three-dimensional image-guided TMI has been developed to enhance mechanistic understanding of the role of TMI and to support the development of experimental therapeutics. However, a dosimetric comparison between preclinical and clinical TMI reveals that the preclinical TMI treatment lacks the ability to reduce the dose to some of the vital organs that are very close to the skeletal system and thus limits the ability to evaluate radiobiological relevance. To overcome this limit, we introduce a novel Sparse Orthogonal Collimator (SOC)-based TMI and evaluate its ability to enhance dosimetric conformality. The SOC-TMI-based dose modulation technique significantly improves TMI treatment planning by reducing radiation exposures to critical organs that are close to the skeletal system that leads to reducing the gap between clinical and preclinical TMI.

Implication of miR-122, miR-483, and miR-335 Expression Levels as Potential Signatures in HCV-Related Hepatocellular Carcinoma (HCC) in Egyptian Patients.

Hepatocellular carcinoma (HCC) is the second most common cause of cancer-related deaths worldwide with chronic hepatitis C virus (HCV) infection as a major risk factor of HCC. Circulating microRNAs are deregulated in HCC and are candidate biomarkers. The aim of this study was to explore the expression profile of miRNA-122, miR-483, and miR-335 in the serum of HCV-related hepatocellular carcinoma (HCC). 90 HCV-related hepatocellular carcinoma (HCC) patients, 90 non-malignant HCV patients, and 60 healthy controls were included. Serum microRNAs were measured by a qRT-PCR custom array. The expression levels of miR-122 and miR-483 were upregulated in HCC patients, while the miR-335 expression level was downregulated versus controls and HCV groups. Receiver-operating characteristic (ROC) curve analysis was created to examine miRNAs. miR-483 presented the best diagnostic potential because it showed the highest diagnostic accuracy for distinguishing HCV-related HCC patients from controls (AUC = 0.98) with 100% sensitivity. Moreover, there was obvious prognostic power in distinguishing HCV from HCC (AUC = 0.95) with 88% sensitivity. In conclusion, studied microRNAs (miR-122, miR-483, and miR-335) could serve as potential non-invasive early diagnostic biomarkers for HCC, and we identified a panel of three serum microRNAs with high accuracy in HCC diagnosis. Additional studies are required to confirm this panel and test its prognostic significance.

Circulating microRNA-944 and its target gene EPHA7 as a potential biomarker for colorectal cancer.

MicroRNAs (miRNAs) have critical roles in colorectal cancer (CRC) tumorigenesis and development. It has been reported that Eph receptor A7 (EphA7) was a potential target of miR-944 which is transcriptionally activated in cancer. The aim of this study was to explore the expression profile of miR-944 and its target gene EPHA7 in the serum of Egyptian CRC patients. 150 CRC patients, 50 adenomatous polyps (AP) patients, and 100 healthy controls were included. Serum miR-944 was downregulated (0.304 ± 0.0512) while serum EPHA7 was upregulated (3.163 ± 0.610) in CRC and AP patients versus controls and discriminated aganst these groups by Receiver operating characteristic curve (ROC) analysis. miR-944 presented the highest diagnostic accuracy for CRC patients from control (AUC = 0.90). Moreover obvious prognostic power in distinguishing AP from CRC (AUC = 0.87). In conclusion, miR-944 and EPHA7 are potential genetic markers of CRC predisposition and novel potential non-invasive diagnostic biomarkers for CRC.

Dasatinib ameliorates thioacetamide-induced liver fibrosis: modulation of miR-378 and miR-17 and their linked Wnt/ß-catenin and TGF-ß/smads pathways.

Hepatic stellate cells activation (HSCs) plays a crucial role in the pathogenesis of liver fibrosis. Specific microRNAs have been suggested to affect the activation of HSCs via various signalling pathways including TGF-ß/smads and Wnt/ß-catenin pathways. Dasatinib is a multitarget inhibitor of many tyrosine kinases has recently studied for its anti-fibrotic effects in a variety of fibrous diseases. This study investigated the role of modulation of miRNA-378 and miRNA-17 in the pathogenesis of liver fibrosis through altering Wnt/ß-catenin and TGF-ß/smads pathways and evaluated the beneficial effect of the tyrosine kinase inhibitor, dasatinib, in thioacetamide-induced liver fibrosis model in mice. Treatment with dasatinib down-regulated miRNA-17 expression, leading to the restoration of WiF-1 and smad-7 which cause the inhibition of both Wnt/ß-catenin and TGF-ß/smads signalling. In addition, it upregulated miRNA-378 leading to the decrease of Wnt-10 which contributes to the suppression of activated HSCs.

The Hepatoprotective Effect of Piperine Against Thioacetamide-Induced Liver Fibrosis in Mice: The Involvement of miR-17 and TGF-ß/Smads Pathways.

Liver fibrosis is characterized by a series of events including activation of quiescent hepatic stellate cells (HSCs) into proinflammatory, contractile, and fibrogenic myofibroblasts, which is the primary trigger for the fibrogenesis process. HSC activation involves many signaling pathways such as the TGF-ß/smads pathway. Specific microRNAs have been identified to play a crucial role in the activation of HSCs via various signaling pathways. Piperine has recently been studied as a promising anti-fibrotic agent against pancreatic fibrosis through altering the TGF-ß1/Smad pathway. Hence, the current study evaluated the beneficial effects of piperine in thioacetamide-induced liver fibrosis in mice through the modulation of miRNA-17 and TGF-ß/smads pathways. Mice were allocated into three groups randomly. Thioacetamide was used to induce liver fibrosis for 6 weeks. Starting from the fourth week of the experiment, mice were treated with piperine daily for 21 days. Piperine treatment resulted in a significant downregulation of miRNA-17 expression, leading to the restoration of smad-7 accompanied with marked inhibition of TGF-ß/smads signaling with further suppression of the activated HSCs and collagen deposition in the hepatocytes. In conclusion, piperine has the potential to be a promising therapeutic drug for the treatment of liver fibrosis through inhibiting the TGF-ß/smads pathway.

The Impact of Single Nucleotide Polymorphism in the Long Non-coding MEG3 Gene on MicroRNA-182 and MicroRNA-29 Expression Levels in the Development of Breast Cancer in Egyptian Women.

Early-stage detection of BC is a critical factor for effective treatment of the disease and can increase the survival rate of BC patients. Long non-coding RNAs can act as miRNA decoys by sequestering miRNAs, thus acting as competing endogenous RNAs and leading to re-expression of miRNA target genes. Maternally expressed 3 (MEG3) is LncRNA and it was reported to be tumor suppressor in breast cancer. The study aims to investigate the effect of MEG3 SNP (rs7158663 G/A) and its association with breast cancer risk in the Egyptian population. In addition, demonstrate the consequence of the MEG3 polymorphism on the expression levels of MEG3, miR-182, and miRNA-29. MEG3 rs7158663 G/A was genotyped and serum MEG3, miRNA-182, and miRNA-29 were measured in 180 breast cancer, 120 FA, and 150 controls by the qPCR. Frequencies of MEG3 rs7158663 GA/AA genotype and A allele were significantly higher in BC patients compared to the controls results showed that serum MEG3 levels were significantly lower, according to the presence of the A allele in different study groups while the expression of miR-182 and miRNA 29 were significantly elevated. MEG3, miR-182, and miRNA-29 are key genes involved in the development of BC, are considered as a novel potential non-invasive diagnostic biomarker for BC.

The role of mirabegron in relieving double-J stent-related discomfort: a randomized controlled clinical trial.

INTRODUCTION: The aim of this study was to investigate the effect of 50 mg mirabegron once daily in relieving ureteral double-J (DJ) stent-related discomfort after ureteroscopy (URS) or retrograde intrarenal surgery (RIRS). MATERIAL AND METHODS: A total of 210 patients who underwent DJ ureteral stent insertion after URS or RIRS were randomized 1:1 to receive either no treatment (Group B) or mirabegron 50 mg once daily (Group A) during the stenting period. At time of stent removal, all patients were evaluated for stent-related symptoms using the Arabic translated and validated ureteral stent symptom questionnaire (USSQ). The severity of stent-related symptoms (SRS) was compared between the two groups. RESULTS: The mean age was 46.6 ±8.2 years in Group A and 44.7 ±9.4 (26-64) years in the control group (p = 0.13). The stone characteristics, stent size, and position were similar in both groups. Compared to the control group, the mirabegron group had significantly lower daytime frequency, nocturia and urgency (p = 0.028, p = 0.008 and p = 0.012, respectively). As for stent-related pain, Group A had significantly less flank and abdominal pain (p = 0.007 and p = 0.001, respectively). The mirabegron versus control group showed significant difference in mean analgesics use and quality of life (QoL) scores during the stenting period (p = 0.005 and p = 0.003, respectively). Three patients (2.9%) in Group A encountered minor adverse effects (two experienced dry mouth and one presented with constipation). CONCLUSIONS: For patients with indwelling DJ stent, postoperative mirabegron 50 mg use was effective and well-tolerated for the treatment of lower urinary tract symptoms and stent-related pain.

Real-world outcomes of patients with locally advanced or metastatic epithelioid sarcoma.

BACKGROUND: Limited data are available on the real-world effectiveness and safety of systemic therapies for advanced (surgically unresectable and/or metastatic) epithelioid sarcoma (ES). METHODS: A retrospective medical records review was conducted in patients with advanced ES who were initiating first-line or ≥2 lines of systemic therapy (2000-2017) at 5 US cancer centers. The real-world overall response rate (rwORR), the duration of response (rwDOR), the disease control rate (rwDCR) (defined as stable disease for ≥32 weeks or any duration of response), and progression-free survival (rwPFS) were assessed by radiology reports. Overall survival (OS), rwDOR, and rwPFS were estimated from the time therapy was initiated using the Kaplan-Meier method. Serious adverse events were assessed. RESULTS: Of 74 patients (median age at diagnosis, 33 years; range, 10.6-76.3 years), 72% were male, and 85% had metastatic disease. The median number of lines of therapy was 2 (range, 1-7 lines of therapy), and 46 patients (62%) received ≥2 lines of systemic therapy. First-line regimens were usually anthracycline-based (54%) or gemcitabine-based (24%). For patients receiving first-line systemic therapy, the rwORR was 15%, the rwDCR was 20%, the median rwDOR was 3.3 months (95% CI, 2.1-5.2 months), the median rwPFS was 2.5 months (95% CI, 1.7, 6.9 months), and the median OS was 15.2 months (95% CI, 11.4-21.7 months). For those who received ≥2 lines of systemic therapy, the rwORR was 9%, the rwDCR was 20%, the median rwDOR was 4.5 months (95% CI, 0.7-5.6 months), and the median rwPFS was 6.0 months (95% CI, 3.2-7.4 months). Over one-half of patients (51.4%) experienced an adverse event, most frequently febrile neutropenia (14%), pain (10%), anemia, dyspnea, fever, thrombocytopenia, or transaminitis (5% each). CONCLUSIONS: Systemic therapies demonstrate limited efficacy in patients with advanced ES and have associated toxicities.

Long-term outcome of non-stented tubularized incised plate urethroplasty for distal hypospadias repair: a complication analysis.

INTRODUCTION: Although it is apparently simpler to perform unstented tubularized incised plate (TIP) repair for distal hypospadias repair, consensus on feasibility of the use of unstented repair is still a matter of debate. Evidence reporting that unstented repair outcome is comparable to stented repair, especially in the long-term, is still weak due to reporting outcome inconsistencies, different study designs, inclusion of more than one technique, and inherent variability in meatal locations. Thus, we need a continuous and evolving assessment of the outcome of unstented repair to compile adequate evidence on the advantage of unstented TIP repair in distal hypospadias entity. The aim of this article was to review our long-term results with tubularized incised plate urethroplasty for distal hypospadias repair without a postoperative stent to determine its outcome which might justify its use. MATERIAL AND METHODS: After a review of 154 patients with distal penile hypospadias, who underwent repair in Minia Urology & Nephrology University Hospital in the period between June 2015 and February 2018, we excluded cases who underwent MAGPI repair, redo cases and patients who failed to complete follow-up. We chose 72 patients who had only 1st time TIP repair and whom we could contact. A total of 44 out of 72 cases with stented repair were assigned to Group A, while 28 cases with unstented repair were assigned to Group B. Success was assessed based on Hypospadias Objective Penile Evaluation (HOPE) score by three separate senior pediatric urology consultants, independent of the surgeon and in the absence of high post-void residual urine (PVR). Average rate was calculated to be compared between both study groups. RESULTS: There was no statistically significant difference regarding preoperative meatal location and age at repair and short-term complications. In the long-term; there was no statistically significant difference between the occurrence of urethrocutanous fistula (UCF, 4 vs 2 cases in Group A & B, respectively) and complete disruption (2 cases in each group) with need for redo repair. Results of total mean of HOPE score calculated showed no statistically significant differences between study groups and also failed to showed statistical significance on individual domains of HOPE score. CONCLUSIONS: Unstented TIP repair showed a similar outcome to stented TIP repair of distal hypospadias especially in the long-term despite a more troublesome early postoperative period.

Applications of Office-Based 445 nm Blue Laser Transnasal Flexible Laser Surgery: A Case Series and Review of Practice.

BACKGROUND: The recent introduction of 445 nm blue laser to office-based laryngology presents potential advantages. These include a desirable combination of cutting and photoangiolytic qualities and a lightweight, shock-resistant design. Despite its increasing use, current evidence is limited to experimental data and case reports. OBJECTIVES: The authors present a case series and overview of office blue laser transnasal flexible laser surgery (TNFLS), considering indications, patient selection, safety, technique, and surgical outcomes. We also review the safety and relevance of TNFLS to the ongoing coronavirus pandemic. METHODS: Retrospective case series and narrative review. Our primary outcome measure was preoperative and postoperative Voice Handicap Index (VHI-10) score. Complications were documented by nature and severity. RESULTS: Thirty-six cases of office blue laser TNFLS were performed. A statistically significant improvement in VHI-10 score was demonstrated in cases of recurrent respiratory papillomatosis (RRP) and benign laryngeal lesions causing dysphonia (P < 0.01 and 0.045). Blue laser also proved effective in assisting office biopsy procedures. A minor and self-limiting complication was reported. CONCLUSIONS: Office blue laser TNFLS is safe and effective in the treatment of RRP and a range of benign laryngeal lesions. Future research should compare the efficacy and safety of blue laser with potassium titanyl phosphate laser in office-based treatment of these conditions. Further assessment of the cutting qualities of blue laser, initially in the theater environment, is necessary to refine our understanding of future applications.

Prevention of stone retropulsion during ureteroscopy: Limitations in resources invites revival of old techniques.

OBJECTIVE: To compare a modified technique using the Dormia basket vs Stone Cone for stone entrapment to avoid proximal stone migration during ureteroscopic pneumatic lithotripsy of ureteric stones. PATIENTS AND METHODS: Our study included all patients with ureteric stones of <15 mm who underwent ureteroscopic pneumatic lithotripsy from January 2015 to September 2018. The study had two arms that were conducted over two consecutive periods; the first included 72 patients in whom we used the Stone Cone (Group 1) and the second included 86 patients in whom we started to use a Dormia basket with a modification (Group 2) to guard against proximal stone migration. RESULTS: Both groups were comparable for gender, age, and stone characteristics. Lower ureteric stones were the most prevalent as they represented 62.5% and 60.5% in groups 1 and 2, respectively; while upper ureteric stones were respectively found in 16.7% and 17.4%. Chemical stone analysis revealed that calcium oxalate stones were most predominant accounting for 51.3% and 51.1% in groups 1 and 2, respectively. Most of the stones were radio-opaque stones representing 57% and 58.1% in groups 1 and 2, respectively. There was a significant difference in operative time, with a mean (SD) operative time was 50.9 (11.2) in Group 1 vs 58.3 (12.4) min in Group 2 (P < 0.001). The success rate, defined as no retropulsion of stone fragments, was 97.7% in Group 2 vs 91.7% in Group 1 (P < 0.01). Complications were minor and comparable between the groups. There was no difference in hospital stay between the groups, but the cost assessment favoured Group 2. CONCLUSION: We found that our modified-basket stone entrapment technique compared favourably with the Stone Cone to guard against stone retropulsion during ureteroscopic pneumatic lithotripsy. Our modification to the basket was found to be feasible, efficient, safe, reproducible and cost-effective in preventing proximal stone migration. This procedure is particularly suitable in cost-limited environments.

Dietary sodium butyrate ameliorated the blood stress biomarkers, heat shock proteins, and immune response of Nile tilapia (Oreochromis niloticus) exposed to heat stress.

The present study investigated the effects of sodium butyrate (SB) on the growth performance, histomorphology, immune response, and stress related markers of Nile tilapia subjected to heat stress. SB was incorporated at 0, 0.5, 1, 1.5, and 2 g per kg diet and fed to fish for 8 weeks. The obtained results revealed significantly improved growth performance with a decreased feed conversion ratio in the fish fed SB (P < 0.05). In the anterior, middle, and distal parts of the intestine, villus length and width and internal villi distance as well as the number of goblet cells were increased in the fish fed SB (P < 0.05). The blood total protein, hemoglobin, and white and red blood cell counts showed a significant quadratic influence (P < 0.05). The survival rate for Nile tilapia exposed to heat stress for 48 h revealed that the SB fed groups had noticeably higher survival rates. Dietary SB significantly increased the phagocytic index and lysozyme and phagocytic activities both before and after heat stress (P < 0.05). After heat stress, blood glucose decreased significantly with SB feeding at 0.5, 1, or 1.5 g per kg diet, while cortisol was reduced in fish fed 1.5 or 2 g per kg diet (P < 0.05). Additionally, in fish fed SB, superoxide dismutase (SOD), catalase, and glutathione peroxidase activities were significantly increased both before and after heat stress, while malondialdehyde was decreased by SB feeding (P < 0.05). Liver heat shock protein 70 and SOD gene expression were significantly upregulated in fish fed on SB at 1 g per kg diet (P < 0.05). Thus, supplementation with SB at 1-2 g per kg diet can be used effectively in tilapia diets for improving growth, feed efficiency, and immune response as well as for tolerance to heat stress.

Prospective comparative study between the effect of CIDEX® OPA and STERRAD NX on the durability of digital flexible ureteroscope.

PURPOSE: We compared the effect of chemical disinfection (CIDEX® OPA) and low-temperature hydrogen peroxide gas plasma (STERRAD NX) on two brand new digital flexible ureteroscope (DFU) (Flex-Xc) using subjective and objective parameters. METHODS: Over 11-month period, all flexible ureteroscopic procedures that fulfill the inclusion criteria were done by two brand new flexible ureteroscopes and were prospectively evaluated. Intraoperative data included total operative time, laser power and duration, stone criteria and subjective evaluation of the procedure as well as visibility and maneuverability scores were reported. The end point of the study was when the scope was deemed by the surgeon as unable to perform the procedure; when leak test is positive. RESULTS: A total of 88 patients were randomized either for the first flexible ureteroscope disinfected using Cidex® OPA (n = 59, 67%) or second ureteroscope sterilized with Sterrad NX (n = 29, 33%). Intraoperative, the first DFU was significantly used with a total operative time of approximately 49 h compared to the second one (p < 0.001). In the same context, laser power parameters were significantly different among the two groups (p = 0.003). The subjective evaluation of the procedure, maneuverability, visibility scores, laser duration, stone burden and post-operative infection rate were statistically insignificant between both groups. At the end point of the study, the deflection in up and downward directions for both DFU were measured. CONCLUSIONS: The durability and longevity of the DFU is strongly related to the sterilization method. Our findings suggest that CIDEX® OPA should prioritize Sterrad in sterilization of DFU.

Outcome of early experience of Miniperc technique in pediatric age group.

BACKGROUND: The aim of this study is to report our experience with the Miniperc technique for treatment of renal stone in pediatric age group. MATERIALS AND METHODS: From August 2012 to January 2015, 34 patients aged <15 years with renal stones <3 cm underwent Miniperc technique were included in our study. The procedure was done through 14 Fr sheath using 8/9.8 Fr semi-rigid ureteroscope, holmium laser, and pneumatic lithotriptor for stone fragmentation. Stone-free rate (SFR), operative time, hospital stay, and complication rate were evaluated. RESULTS: A total of 34 Miniperc techniques were performed on children with a mean age of 8.8 ± 3.7 years. Stone size varied from 18 to 30 mm (mean 23 mm). Mean operative time was 50 min. The mean hospital stay was 48±12 hours. The overall SFR was 82.4% which increased after secondary procedures to 94%. Two postoperative complications recorded in the form of sepsis and bleeding that required no blood transfusion. CONCLUSION: Our initial experience concluded that Miniperc technique is a safe and effective treatment option for renal stones in pediatric population.

The Protective Effect of Korean Red Ginseng Against Rotenone-Induced Parkinson's Disease in Rat Model: Modulation of Nuclear Factor-κß and Caspase-3.

OBJECTIVE: Korean red ginseng was reported to have many biological effects like the antioxidant and the anti-inflammatory activities. Oxidative stress and neuro-inflammation play major roles in the pathogenesis of Parkinson's disease (PD). The current study aimed to investigate the protective effects of ginseng on rotenone-induced PD in rats. METHODS: Rats were randomly allocated into 4 groups: normal rats, rotenone control, ginseng+rotenone and ginseng only treated rats. The severity of PD was evaluated through locomotor activity perceived in the open field test, histological examination and immunohistochemical detection of amyloid-ß in brain tissues, in addition to the biochemical assessment of tyrosine hydroxylase activity in brain tissues. Moreover, the following parameters were investigated for studying the possible mechanisms of ginseng neuroprotective effect: nuclear factor-κß (NF-κß), tumor necrosis factor-alpha (TNF-α), caspase- 3, lipid peroxides and reduced glutathione (GSH). RESULTS: Ginseng exhibited potent neuroprotective effect that was reflected upon the histopathological examination, marked improvement in the locomotor activity and through its ability to suppress the amyloid- ß deposition in the cortex and striatum along with significant increase in the tyrosine hydroxylase activity. Ginseng successfully inhibited the NF-κß inflammatory pathway in brain tissues beside the inhibition of other oxidative stress and inflammatory mediators. Furthermore, it exhibited antiapoptotic effect via the inhibition of caspase-3 expression. CONCLUSION: Ginseng could be a promising treatment in PD. It can suppress dopaminergic neuron degeneration through variable mechanisms mainly via inhibition of NF-κß pathway in addition to inhibition of oxidative stress and apoptosis.