Optimum combined MET according to tolerability with efficacy, Silodosin Tadalafil versus Silodosin Vardenafil for distal ureteric stone: a prospective, double blinded, randomized clinical trial.

OBJECTIVES: To determine the optimum combination therapy of Silodosin-Tadalafil versus Silodosin-Vardenafil in terms of both tolerability and efficacy for the management of distal ureteric stones. METHODS: This prospective, double blinded, randomized clinical trial included 140 patients with distal ureteric stones, randomized into two groups: Group I (n = 67) received Silodosin 8 mg once daily combined with Tadalafil 5 mg once daily, and Group II (n = 68) received Silodosin 8 mg once daily combined with Vardenafil 10 mg once daily. The primary outcome was the tolerability of the combination therapies, assessed through the incidence of adverse events. Secondary outcomes included stone expulsion rate, expulsion time, and the need for analgesics. RESULTS: Both combination therapies demonstrated similar efficacy, with no significant differences in stone expulsion rate (70.1% vs. 67.6%, P = 0.754), expulsion time (19 ± 3 days for both groups, P = 0.793), and analgesic requirements (P > 0.05). However, the Silodosin-Tadalafil combination showed a significantly lower occurrence of adverse events, with notable differences in headache (23.9% vs. 57.4%, P < 0.001), dizziness (32.8% vs. 60.3%, P = 0.001), and gastrointestinal upset (9% vs. 66.2%, P < 0.001), and other adverse effects. The overall occurrence of any adverse event was significantly lower in the Silodosin-Tadalafil group (88.1% vs. 98.5%, P = 0.017). CONCLUSIONS: Both Silodosin-Tadalafil and Silodosin-Vardenafil therapies are effective in managing distal ureteric stones. However, the Silodosin-Tadalafil combination is associated with a significantly lower incidence of adverse events, making it a more tolerable option for patients.

Effectiveness and safety of secukinumab updosing in patients with moderate to severe plaque psoriasis: data from the PURE registry.

Secukinumab is a fully human IgG1 antibody that selectively binds to and neutralizes the proinflammatory cytokine interleukin-17A. Secukinumab is an effective and well-tolerated treatment for plaque psoriasis. There is a limited real-word evidence for dose optimisation of secukinumab based on clinical response. PURE is a multi-national, prospective, observational study in patients with moderate to severe chronic plaque psoriasis in Canada and Latin America, assessing the real-world safety and effectiveness of secukinumab and other indicated therapies. The aim of the current snapshot analysis was to evaluate the effectiveness and safety of on-label dose and updosed secukinumab in patients with plaque psoriasis enrolled in the PURE study. At the time of analysis, 676 patients received secukinumab, of which 84.6% (n = 572) remained on the on-label dose, while 15.4% (n = 104) were updosed. With on-label secukinumab, the absolute Psoriasis Area and Severity Index (PASI) score was reduced from 13.6 at baseline to 1.2 over 36 months, with treatment persistence of 73% at 40 months. At Month 36, 73.2% of the patients receiving on-label secukinumab achieved Investigator's Global Assessment (IGA) 0/1. With updosed secukinumab (300 mg every 2 weeks, 300 mg every 3 weeks, 450 mg every 4 weeks, or 450 mg every 3 weeks), 57.9% of the patients showed improvement in the absolute PASI score at the first visit after updosing, with treatment persistence of 50% at 12 months after updosing. At Month 15, 40% of patients receiving updosed secukinumab achieved IGA 0/1. Patients with previous biologic exposure (odds ratio [OR]: 3.25; 95% confidence interval [CI]: 2.03, 5.18, p < 0.0001) were more likely to be updosed while those with a body weight < 90 kg (OR: 0.49; 95% CI [0.31, 0.77], p = 0.0019) were less likely to be updosed. Previous biologic exposure (HR [hazard ratio]: 1.47; 95% CI [1.24, 1.75], p < 0.0001) and current biologic exposure (secukinumab vs. other indicated therapies: HR 0.57; 95% CI [0.43, 0.75], p = 0.0001) were significantly associated with time to secukinumab updosing. No new or unexpected safety signals were observed with updosed secukinumab. Secukinumab updosing was efficacious and well-tolerated in patients with psoriasis who failed to respond to the approved on-label regimen, suggesting that updosing may be a useful therapeutic option for approved dose non-responders.

Predicting stone free rate after retrograde intrarenal surgery using RIRS scoring system versus Resorlu Unsal stone score (RUSS).

Background: To evaluate the predictive ability of the RIRS scoring system and the RUSS in predicting stone-free rate (SFR) after retrograde intrarenal surgery (RIRS). Methods: This prospective study was conducted on patients who underwent RIRS for kidney stones. Two scoring systems were used to determine the degree of procedure difficulty: the RIRS scoring system and the RUSS. We assessed the predictive ability of the two scoring systems utilizing receiver operating characteristic (ROC) analysis and calculated the sensitivity and specificity of each system. Additionally, we analyzed the association between the scoring systems and the stone-free outcome using a multivariate logistic regression model. Results: One hundred seventy-one patients were incorporated into this study with a mean age of 43 years, and 65.5% were male. The results showed a significant AUC of 0.868 for the RIRS score (P < 0.001, 95% CI = 0.813-0.924). The sensitivity and specificity were 72% and 93.7%, respectively. In contrast, the RUSS score revealed a non-significant unsatisfactory AUC of 0.480 (P = 0.660), with a 95% confidence interval ranging from 0.384-0.576. Conclusion: The RIRS scoring system showed a better predictive ability for SFR after RIRS than the RUSS. Additionally, RIRS was a significant predictor of SFR, controlling for age, gender, body mass index, and previous renal surgery.

Elective paraesophageal hernia repair in elderly patients: an analysis of ACS-NSQIP database for contemporary morbidity and mortality.

BACKGROUND: Elective paraesophageal hernia (PEH) repair in asymptomatic or minimally symptomatic patients ≥ 65 years of age remains controversial. The widely cited Markov Monte Carlo decision analytic model recommends watchful waiting in this group, unless the mortality rate for elective repair was to reach ≤ 0.5%; at which point, surgery would become the optimal treatment. We hypothesized that with advances in minimally invasive surgery, perioperative care, and practice specialization, that mortality threshold has been reached in the contemporary era. However, the safety net would decrease as age increases, particularly in octogenarians. METHODS: We identified 12,422 patients from the 2015-2017 ACS-NSQIP database, who underwent elective minimally invasive PEH repair, of whom 5476 (44.1%) were with age ≥ 65. Primary outcome was 30-day mortality. Secondary outcomes were length of stay (LOS), operative time, pneumonia, pulmonary embolism, unplanned intubation, sepsis, bleeding requiring transfusion, readmission, and return to OR. RESULTS: Patients age ≥ 65 had a higher 30-day mortality (0.5% vs 0.2%; p < 0.001). Subset analysis of patients age 65-80 and > 80 showed a 30-day mortality of 0.4% vs. 1.8%, respectively (p < 0.001). Independent predictors of mortality in patients ≥ 65 years were age > 80 (OR 5.23, p < 0.001) and COPD (OR 2.59, p = 0.04). Patients ≥ 65 had a slightly higher incidence of pneumonia (2% vs 1.2%; p < 0.001), unplanned intubation (0.8% vs 0.5%; p < 0.05), pulmonary embolism (0.7% vs 0.3%; p = 0.001), bleeding requiring transfusion (1% vs 0.5%; p < 0.05), and LOS (2.38 vs 1.86 days, p < 0.001) with no difference in sepsis, return to OR or readmission. CONCLUSION: This is the largest series evaluating elective PEH repair in the recent era. While morbidity and mortality do increase with age, the mortality remains below 0.5% until age 80. Our results support consideration for a paradigm shift in the management of patients < 80 years toward elective repair of PEH.

Taurine alleviates kidney injury in a thioacetamide rat model by mediating Nrf2/HO-1, NQO-1, and MAPK/NF-κB signaling pathways.

This study investigated the molecular mechanisms by which taurine exerts its reno-protective effects in thioacetamide (TAA) - induced kidney injury in rats. Rats received taurine (100 mg/kg daily, intraperitoneally) either from day 1 of TAA injection (250 mg/kg twice weekly for 6 weeks) or after 6 weeks of TAA administration. Taurine treatment, either concomitant or later as a therapy, restored kidney functions, reduced blood urea nitrogen (BUN), creatinine, and malondialdehyde (MDA), increased renal levels of superoxide dismutase (SOD), and reversed the increase of kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) caused by TAA. Taurine treatment also led to a significant rise in nuclear factor erythroid 2-related factor 2 (Nrf2), hemoxygenase-1 (HO-1), and NADPH quinone oxidoreductase-1 (NQO-1) levels, with significant suppression of extracellular signal-regulated kinase (ERK) 1/2, nuclear factor kappa B (NF-κB), and tumor necrosis factor α (TNF-α) gene expressions, and interleukin-18 (IL-18) and TNF-α protein levels compared with those in TAA kidney-injured rats. Taurine exhibited reno-protective potential in TAA-induced kidney injury through its antioxidant and anti-inflammatory effects. Taurine antioxidant activity is accredited for its effect on Nrf-2 induction and subsequent activation of HO-1 and NQO-1. In addition, taurine exerts its anti-inflammatory effect via regulating NF-κB transcription and subsequent production of pro-inflammatory mediators via mitogen-activated protein kinase (MAPK) signaling regulation.

Thymoquinone dose-dependently attenuates myocardial injury induced by isoproterenol in rats via integrated modulations of oxidative stress, inflammation, apoptosis, autophagy, and fibrosis.

As rats develop myocardial infarction (MI) like lesions when injected with large doses of isoproterenol (ISO), this investigation was designed to evaluate the dose-dependent effects of thymoquinone (TQ) on ISO-induced myocardial injury in rats. Adult male rats were divided into negative control, TQ20 (20 mg/kg/day), TQ50 (50 mg/kg/day), ISO positive control, TQ20 + ISO, and TQ50 + ISO groups. In these rats, biochemical, immunobiochemical, and histopathological studies were carried out to evaluate myocardial oxidative stress, inflammation, apoptosis, fibrosis, and autophagy, and the changes in serum cardiac biomarkers. The results showed that TQ pretreatment in ISO-administered rats produced a dose-dependent significant reduction of the myocardial infarct size, markedly reduced the ISO-induced elevation in serum cardiac markers and demonstrated several other important findings related to the cardioprotective efficacy of TQ. First, this study is the first reported research work showing that TQ treatment could increase the myocardial reduced glutathione baseline level, adding an indirect antioxidant effect to its known direct free radical scavenging effect. Second, pretreatment with TQ significantly reduced the markers of myocardial oxidative stress, inflammation, fibrosis, and apoptosis. Third, TQ acted as an autophagy enhancer ameliorating myocardial cell damage and dysfunction. Thus, the morphological and biochemical changes associated with ISO-induced myocardial injury were ameliorated with TQ pretreatment. The extent of this improvement was significantly greater in the TQ50 + ISO group than in the TQ20 + ISO group. The present study, for the first time, demonstrates these dose-dependent effects of TQ in experimentally induced myocardial injury. These findings raise the possibility that TQ may serve as a promising prophylactic cardioprotective therapy for patients who are at risk of developing myocardial injury and against the progression of existent myocardial injury as in cases of MI.

Distinct Proteins in Protein Corona of Nanoparticles Represent a Promising Venue for Endogenous Targeting - Part II: In vitro and in vivo Kinetics Study.

INTRODUCTION: Nanoparticles (NPs), upon introduction to the biological systems, become wrapped by serum and cellular proteins constituting the protein corona (PC). This PC contributes largely to the NPs' interaction with the biological systems and their subsequent functions. On the one hand, PC can decrease the efficiency of targeting by directing the NPs to the reticuloendothelial system (RES) or by masking the active targeting moieties and decreasing their ability to bind to their target receptors. On the other hand, some components of PC have offered hopes for achieving endogenous targeting. METHODS: In this study, we aimed at the investigation of the role of the PC in determining the behavior of cRGDyk peptide-unconjugated and -conjugated NPs (uNPs and cNPs) exhibiting different physicochemical properties and their interaction with melanoma on in vitro and in vivo levels. Mathematical modeling has been utilized to understand the kinetics of the interaction of NPs with the tumor cells and different organs, respectively. RESULTS: Endocytosis and exocytosis were reported to occur simultaneously for the utilized NPs. The balance was largely dependent on the NPs' physicochemical properties and the role of the PC. In addition, distinct proteins present in the PC (illustrated in the results of the PC analysis in part I) have also determined the patterns of the NPs' distribution in different organs and tissues of the vascular system, the RES system and the target tumot tissue. Vitronectin (VN) was found to mediate higher accumulation in integrin receptor-expressing melanoma cells, while complement 3 protein (C3) and clusterin (CLU), as an opsonin and dysopsonin, respectively, regulated the balance between the RES uptake and blood circulation. DISCUSSION: PC, if properly modulated by tuning NPs' physicochemical properties, can serve as a potential venue for optimum utilization of NPs in cancer therapy.

Distinct Proteins in Protein Corona of Nanoparticles Represent a Promising Venue for Endogenous Targeting - Part I: In vitro Release and Intracellular Uptake Perspective.

INTRODUCTION: Protein corona (PC) deposition on nanoparticles (NPs) in biological systems contributes to a great extent to NPs' fates; their targeting potential, the interaction with different biological systems and the subsequent functions. PC - when properly tuned - can serve as a potential avenue for optimization of NPs' use in cancer therapy. METHODS: Poly-lactic co-glycolic acid (PLGA)-based NPs exhibiting different physicochemical properties were fabricated and characterized. The PC makeup of these NPs were qualitatively and quantitatively analyzed by Western blot and Bradford assay, respectively. The effect of PC on the release of NPs' cargos and the intracellular uptake into B16F10 melanoma cells has been studied. RESULTS: The composition of NPs (polymeric PLGA NPs vs lipid-polymer hybrid NPs) and the conjugation of an active targeting ligand (cRGDyk peptide) represented the major determinants of the PC makeup of NPs. The in vitro release of the loaded cargos from the NPs depended on the PC and the presence of serum proteins in the release medium. Higher cumulative release has been recorded in the presence of proteins in the case of peptide conjugated NPs, cNPs, while the unconjugated formulations, uNPs, showed an opposite pattern. NPs intracellular uptake studies revealed important roles of distinct serum and cellular proteins on the extent of NPs' accumulation in melanoma cells. For example, the abundance of vitronectin (VN) protein from serum has been positively related to the intracellular accumulation of the NPs. CONCLUSION: Careful engineering of nanocarriers can modulate the recruitment of some proteins suggesting a potential use for achieving endogenous targeting to overcome the current limitations of targeted delivery of chemotherapeutic agents.

Total Thyroidectomy Versus Lobectomy in Small Nodules Suspicious for Papillary Thyroid Cancer: Cost-Effectiveness Analysis.

OBJECTIVES/HYPOTHESIS: Recent American Thyroid Association Guidelines recommend either near-total/total thyroidectomy or lobectomy for patients with a thyroid nodule suspicious for papillary thyroid cancer (PTC) on fine-needle aspiration (FNA) biopsy (Bethesda V). In this analysis, we aim to assess the cost-effectiveness of lobectomy in comparison to total thyroidectomy. STUDY DESIGN: Cost-effectiveness analysis. METHODS: A Markov model cost-effectiveness analysis was performed for a base case followed for 20 years postoperatively. Cost and probabilities data were retrieved from the current literature. Effectiveness was represented by quality-adjusted life year (QALY). RESULTS: Total thyroidectomy protocol produced an incremental cost of $2,681.36 and incremental effectiveness of -0.24 QALY as compared to lobectomy protocol (incremental cost-effectiveness ratio [ICER] = -$11,188.85/QALY). Sensitivity analysis demonstrated that total thyroidectomy becomes a cost-effective strategy only if the risk of stages III and IV PTC is 82.4% among patients with suspicious PTC on preoperative FNA. Lobectomy is cost effective and preferred over total thyroidectomy as long as lobectomy complications are less than 50%. CONCLUSIONS: Total thyroidectomy is not just cost prohibitive but also associated with a lower effectiveness compared to lobectomy. LEVEL OF EVIDENCE: 2c Laryngoscope, 2020.

Towards Reinforcing Healthcare 4.0: A Green Real-Time IIoT Scheduling and Nesting Architecture for COVID-19 Large-Scale 3D Printing Tasks.

With declaring the highly transmissible COVID-19 as a pandemic, an unprecedented strain on healthcare infrastructures worldwide occurred. An enormous shortage in the personal protective equipment (PPE) and the spare parts (SP) for the mechanical ventilators ensued as a consequence of the failure of the centralized global supply chains. Additive manufacturing and Industrial Internet of Things (IIoT), as the pillars of Industry 4.0, arose as the robust noncentralized alternatives. When gathered and properly managed in the IIoT, 3D Printers (3DPs) can complement and support Healthcare 4.0 to face the current and future pandemics. Thus, this paper proposes a real-time green allocation and scheduling architecture designed and dedicated particularly for the large-scale distributed 3D printing tasks (3DPTs) of both PPE and SPs. Our proposed architecture comprises; a broker (B) and a cluster manager (CM). Dynamic status check for the 3DPs and admission control for 3DPTs are among the interconnected roles of CM. CM also performs task allocation and scheduling according to our proposed Online Ascending Load-Balancing Modified Best-Fit (OALMBF) allocation algorithm and Green Real-time Nesting Priority-Based Adaptive (GRNPA) scheduling algorithm. The performance of the proposed architecture was investigated under extremely high-load environments which resulted in a success ratio and a response rate of 99.9667% and 10.9665 seconds, respectively, for the 3000 3DPTs trial. These results proved the robustness and the scalability of our architecture that surpasses its state-of-the-art counterparts. Besides respecting the real-time requirements of the 3DPTs, the proposed architecture improves the utilization of the 3DPs and guarantees an even workload distribution.

Gender disparities are present in academic rank and leadership positions despite overall equivalence in research productivity indices among senior members of American Head and Neck Society (AHNS) Fellowship Faculty.

BACKGROUND: This study aims to examine potential disparities in scholarly performance based on sex, academic rank, leadership positions, and regional distribution of faculty in accredited Head and Neck Surgery fellowships in the United States. METHODS: Online faculty listings for 37 accredited fellowships were organized according to academic rank, leadership position, sex, and institutional location. Academic productivity was measured with three bibliometric indices: h-index, m-index, and the weighted relative citation ratio. RESULTS: A total of 732 faculty members were included, of which 153 (21%) were female. Fifty-eight males (89.2%) held leadership positions, compared to seven females (10.8%). There was no significant difference in overall productivity between male and female senior faculty. There were regional differences in productivity by sex. CONCLUSIONS: Females are underrepresented in senior faculty and within three common leadership positions, although scholarly productivity for male and female senior faculty and for those in leadership positions is similar.

Thyroid surgery and obesity: Cohort study of surgical outcomes and local specific complications.

INTRODUCTION: Obesity is associated with numerous complications after elective general surgeries. The aim is to compare surgical outcomes and local specific complications in obese and non-obese patients after thyroid surgery. METHODS: Retrospective study over a 3-year period at a North American academic institution. Outcome measures were operative time, estimated blood loss, hospital length of stay, and local specific complications (hypocalcemia, recurrent laryngeal nerve injury, wound hematoma, wound seroma, and chyle leakage). RESULTS: A total of 469 patients were included (mean [SD] age, 50.11 [15.01] years; mean [SD] BMI, 30.5 [8.3] kg/m2; 207 [44.14%] obese). There was no difference in operative time (125.7 vs. 129.6, p = 0.52), estimated blood loss (16.88 vs. 14.56, p = 0.28), or hospital length of stay (0.95 vs. 0.95, p = 0.96). Overall, there was no difference in the rates of local specific complications between the two groups. CONCLUSIONS: Obesity is not associated with adverse outcomes in patients undergoing thyroid surgery.

Superior protective effects of febuxostat plus alpha-lipoic acid on renal ischemia/reperfusion-induced hepatorenal injury in rats.

A complex cascade of pathological events including oxidative stress and inflammation is involved in ischemia/reperfusion (I/R)-induced local and remote organ injuries. This study was performed to evaluate the effects of febuxostat (FEB), a selective xanthine oxidase (XO) inhibitor, and alpha-lipoic acid (ALA), a strong antioxidant, on the kidney and liver changes induced by renal I/R in rats. Renal I/R was induced in rats by clamping renal pedicles for 1 h followed by 2 h reperfusion. Fifty rats were assigned to five groups as follows: sham operated; vehicle + I/R; FEB + I/R; ALA + I/R, and (FEB + ALA) + I/R. Drug treatment was given 24 h and 1 h before I/R induction. Serum and tissue biochemical parameters and histopathological changes were examined after reperfusion. Serum creatinine, urea and uric acid levels, and alanine aminotransferase and aspartate aminotransferase activities were elevated after renal I/R. An increase in XO, myeloperoxidase, and malondialdehyde levels was observed in kidney and liver tissues with a concomitant decrease in both the glutathione level and superoxide dismutase activity. In addition, kidney and liver sections of vehicle-pretreated rats subjected to I/R exhibited a pronounced alteration in microanatomy. FEB, ALA, or FEB + ALA pretreatment attenuated the serum and tissue biochemical changes with amelioration of the histopathological changes in both the kidney and liver. The findings of this study revealed that FEB in combination with ALA had a greater protective effect than either drug alone. Thus, FEB and ALA co-administration may provide a potential superior therapeutic strategy to protect the kidney and liver against renal I/R-induced injury.

Well-differentiated thyroid cancer and robotic transaxillary surgery at a North American institution.

BACKGROUND: Recent studies from Asia have reported the safety and feasibility of robotic-assisted thyroid surgery. In the United States, several small series and case reports have been published, mostly regarding treatment of benign disease. The aim of our study is to report the safety and feasibility of robotic surgery for well-differentiated thyroid cancer patients at a North American institution. MATERIALS AND METHODS: We performed a retrospective cohort study using a prospectively collected single-center clinical database at Tulane University Medical Center. We included all well-differentiated thyroid cancer patients who underwent robotic-assisted or conventional cervical approach thyroid surgery with or without lymph node dissections at our institution from January 2015 to June 2017. Patient demographics and perioperative data were collected and analyzed. RESULTS: A total of 144 surgeries for thyroid cancer were performed; 35 (24.3%) were robotic-assisted. There were no significant differences in estimated blood loss, operative times, complication rates, specimen sizes, positive microscopic margins, number of lymph nodes removed with associated lymph node dissections, patient follow-up duration, or clinical recurrence rates between the two groups. Overall length of stay was shorter for robotic-assisted surgery, at 0.6 ± 0.9 d, versus 1.1 ± 1.2 d for conventional open surgery (P = 0.009). For robotic-assisted surgery, 19 patients (54.3%) were discharged on the day of procedure, and only one patient was admitted as inpatient to the hospital (2.9%). CONCLUSIONS: Robot-assisted thyroid surgery is a safe, feasible, and oncologically sound approach for a select group of well-differentiated thyroid cancer patients. However, long-term studies are needed.

Selective parathyroid venous sampling in primary hyperparathyroidism: A systematic review and meta-analysis.

OBJECTIVE: Minimally invasive parathyroidectomy requires accurate preoperative localization techniques. There is considerable controversy about the effectiveness of selective parathyroid venous sampling (sPVS) in primary hyperparathyroidism (PHPT) patients. The aim of this meta-analysis is to examine the diagnostic accuracy of sPVS as a preoperative localization modality in PHPT. METHODS: Studies evaluating the diagnostic accuracy of sPVS for PHPT were electronically searched in the PubMed, EMBASE, Web of Science, and Cochrane Controlled Trials Register databases. Two independent authors reviewed the studies, and revised quality assessment of diagnostic accuracy study tool was used for the quality assessment. Study heterogeneity and pooled estimates were calculated. RESULTS: Two hundred and two unique studies were identified. Of those, 12 studies were included in the meta-analysis. Pooled sensitivity, specificity, and positive likelihood ratio (PLR) of sPVS were 74%, 41%, and 1.55, respectively. The area-under-the-receiver operating characteristic curve was 0.684, indicating an average discriminatory ability of sPVS. On comparison between sPVS and noninvasive imaging modalities, sensitivity, PLR, and positive posttest probability were significantly higher in sPVS compared to noninvasive imaging modalities. Interestingly, super-selective venous sampling had the highest sensitivity, accuracy, and positive posttest probability compared to other parathyroid venous sampling techniques. CONCLUSION: This is the first meta-analysis to examine the accuracy of sPVS in PHPT. sPVS had higher pooled sensitivity when compared to noninvasive modalities in revision parathyroid surgery. However, the invasiveness of this technique does not favor its routine use for preoperative localization. Super-selective venous sampling was the most accurate among all other parathyroid venous sampling techniques. Laryngoscope, 2662-2667, 2018.

Obstructive sleep apnea and stroke.

Obstructive Sleep Apnea (OSA) is a common co-morbid condition in stroke patients. It represents a very important risk factor for stroke in addition to the other established ones such as hypertension, cardiovascular disease (CVD), hyperlipidemia, atrial fibrillation (AF), type 2 diabetes mellitus (T2DM), stress, smoking, and heavy drinking. Although in the United States the prevalence of OSA has somewhat decreased from the previous years, globally its prevalence remains constant, or in some cases, is on the rise. In this review we present the epidemiology for OSA in stroke populations and discuss the risk factors for stroke as well as the underlying pathogenetic mechanisms linking OSA, stroke and CVD. We also emphasize the more thorough evaluation and control of OSA in order to prevent the disabling side effects of a stroke, which not only compromises the physical and mental health of a person and increases the burden on families, but also adds a severe burden to national health economics. OSA should always be considered when assessing a patient with transient ischemic attacks (TIA). Work up and treatment for OSA will not only help prevent stroke with its devastating consequences, but will also help prevent CVD, and ameliorate co-morbid conditions such as diabetes and hypertension in these vulnerable populations.

Hepatorenal protection in renal ischemia/reperfusion by celecoxib and pentoxifylline.

BACKGROUND: Renal ischemia/reperfusion (I/R) is a major clinical problem. Its pathogenesis is multifactorial involving oxidative stress, cytokine overproduction, and inflammatory responses in the kidney and remote organs. This study was performed to evaluate the effects of celecoxib (CEB) and pentoxifylline (PTX) on kidney and liver changes after renal I/R in rats. MATERIALS AND METHODS: Renal ischemia was induced by clamping renal pedicles for 1 h followed by reperfusion for another 1 h. The rats were assigned to five groups: sham control, untreated I/R, CEB + I/R, PTX + I/R, and (CEB + PTX)+I/R. Drug treatment was given for 7 d before I/R. Serum and tissue biochemical and histomorphologic changes were evaluated after reperfusion. RESULTS: Renal I/R caused changes in kidney and liver histology with a significant reduction in the function of both organs. An increase in tumor necrosis factor-alpha, myeloperoxidase, and malondialdehyde levels with a decrease in glutathione content and superoxide dismutase activity was observed in kidney and liver tissues. Pretreatment with CEB, PTX, or CEB + PTX attenuated all these changes and the extent of improvement was similar in all drug-treated groups. CONCLUSIONS: This study is the first experimental work demonstrating the simultaneous nephroprotective and hepatoprotective effects of CEB and PTX after renal I/R. It seems likely that both drugs protect the kidney and liver by reducing oxidative stress, attenuating tumor necrosis factor-alpha production and inhibiting neutrophil tissue infiltration. No additive protective effects were observed in rats received the combined treatment. Thus, our results may imply a promising therapeutic approach by using CEB or PTX to protect the kidney and liver against the hazardous consequences of renal I/R.

Thymoquinone improves the kidney and liver changes induced by chronic cyclosporine A treatment and acute renal ischaemia/reperfusion in rats.

OBJECTIVES: This study was designed to evaluate the effects of chronic cyclosporine A (CsA) treatment and acute renal ischaemia/reperfusion (I/R) on the kidney and liver in thymoquinone (TQ)-treated rats. METHODS: In the CsA study, adult male rats were divided into control, CsA (25 mg/kg per day), TQ (10 mg/kg per day) and CsA + TQ groups, and rat treatment was for 28 days. In the I/R study, adult male rats were divided into sham-operated, I/R (renal ischaemia for 60 min followed by 60 min reperfusion) and TQ + I/R (TQ 10 mg/kg, 24 h and 1 h before ischaemia) groups. KEY FINDINGS: CsA treatment and renal I/R caused kidney and liver dysfunction as evaluated by histopathological changes and biochemical parameters. TQ treatment reduced elevated serum indices back to control levels and ameliorated CsA-induced kidney and liver histopathological changes. In renal and hepatic tissues, CsA and renal I/R induced significant increases in malondialdehyde levels with significant decreases in reduced glutathione levels and superoxide dismutase activities. Such changes in oxidative stress markers were counteracted by TQ treatment. CONCLUSIONS: Kidney and liver injury due to CsA or renal I/R can be significantly reduced by TQ, which resets the oxidant/antioxidant balance of the affected organs through scavenging free radicals and antilipoperoxidative effects.

Characteristics of starch-based biodegradable composites reinforced with date palm and flax fibers.

The aim of this work is to study the behavior of completely biodegradable starch-based composites containing date palm fibers in the range from 20 to 80 wt%. Hybrid composites containing date palm and flax fibers, 25 wt% each, were also examined. The composites were preheated and then hot pressed at 5 MPa and 160°C for 30 min. SEM investigation showed strong adhesion between fibers and matrix. Density measurements showed very small void fraction (less than 0.142%) for composites containing up to 50 wt% fiber content. Increasing fiber weight fraction up to 50 wt% increased the composite static tensile and flexural mechanical properties (stiffness and strength). Composite thermal stability, water uptake and biodegradation improved with increasing fiber content. The present work shows that starch-based composites with 50 wt% fibers content have the optimum mechanical properties. The hybrid composite of flax and date palm fibers, 25 wt% each, has good properties and provides a competitive eco-friendly candidate for various applications.

Impact of chronic nicotine administration on bone mineral content in young and adult rats: a comparative study.

The aim of this study was to evaluate the effects of chronic nicotine administration on bone mineral homeostasis in rapidly growing young rats in comparison to effects in adult male rats. Two doses of nicotine (3 and 4.5mg/kg/day, as nicotine hydrogen tartrate) were used and rat treatment was continued for 6 months. In this study, all nicotine-treated rats weighed less than control rats and the effect was dose-dependent. Also, rats treated with nicotine had lower femoral wet weight and showed a significant reduction in femoral mid-shaft cortical width and femoral and lumbar vertebral ash weights. These effects were associated with a significant reduction of ash calcium and phosphorus contents of the femora and lumbar vertebrae. The bone mineral-lowering effects of nicotine were more severe in the lumbar vertebral spongy bone than in the femoral compact bone and these changes were more marked in adult rats than in young rats. An additional interesting observation was that the femora of young rats treated with nicotine were significantly shorter than those of control young rats. Also, the values of the femoral ash weight per unit length were significantly decreased in nicotine-treated adult rats but not in nicotine-treated young rats. Thus, these results show that nicotine-induced changes in bone vary with age. The clinical relevance of this study is that it may provide justification to insist that all people in general and the risky young group in particular should be warned against the hazards of the negative effects of nicotine on bone.