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Unfortunately, humanity is exposed to mixed plasticizers such as bisphenol-A (BPA) and dibutyl phthalate (DBP) that are leached from the daily used plastic products. Previous studies have demonstrated their potential in pancreatic beta cell injury and diabetes induction. The study hypothesized that both compounds would affect the pancreatic alpha cells in albino rats when administered at environmentally relevant doses. Heat shock protein 60 (HSP60) and caspase-3 protein expression was also investigated as potential mechanisms. Thirty-six male Wistar albino rats were separated into four equal groups: control, BPA alone, DBP alone, and BPA + DBP combined groups. BPA and DBP were given in drinking water for 45 days in a dose of 4.5 and 0.8 µg/L, respectively. Fasting blood glucose, serum insulin, pancreatic tissue levels of malondialdehyde, and superoxide dismutase were measured. Pancreatic sections were subjected to hematoxylineosin (HE) staining, glucagon, HSP60, and caspase-3 immunohistochemistry. Although all three experimental groups showed diffuse islet cell HSP60 immunoreactivity, rats exposed to BPA alone showed α-cell-only apoptosis, indicated by HE changes and caspase-3 immunoreactivity, associated with reduced glucagon immunoreaction. However, rats exposed to DBP alone showed no changes in either α or β-cells. Both combined-exposed animals displayed α and β apoptotic changes associated with islet atrophy and reduced glucagon expression. In conclusion, the study suggested HSP60/caspase-3 interaction, caspase-3 activation, and initiation of apoptosis in α-cell only for BPA-alone exposure group, meanwhile DBP alone did not progress to apoptosis. Interestingly, both α/β cell effect was observed in the mixed group implying synergetic/additive action of both chemicals when combined.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder of fertile females. It has been reported that stevia leaf extract (SLE) has antidiabetic and antihyperlipidemic properties. Therefore, the current study hypothesized and investigated the role and mechanistic aspects of a natural sweetener; SLE in treating a rat model of letrozole-induced PCOS and to compare it with metformin. Thirty-five female Wistar albino rats were divided into 5 groups: control, PCOS-induced group (letrozole, 1 mg/kg/d, for 21 days), SLE, metformin, and combination-treated groups (300 mg/kg/d, for the next 28 days in SLE and metformin-treated groups). Vaginal smears were done. The levels of glucose, lipid, and hormonal profiles were measured in the serum meanwhile, malonyl dialdehyde (MDA), superoxide dismutase (SOD), and tumour necrosis factor (TNF-α) were measured in the ovary. Ovarian sections were subjected to hematoxylin and eosin, Masson, and immunohistochemical identification of VEGF and TGF-β followed by morphometric analysis. PCOS rats showed altered hormonal and lipid profiles, in addition to hyperglycemia. Also, the ovarian tissue levels of MDA and TNF-α were elevated, and SOD was decreased. Numerous cystic follicles, decrease/absence of corpora lutea, interstitial fibrosis with positive VEGF and TGF-β immunoreactivity were evident. SLE improved all altered parameters. SLE showed potential therapeutic merits in letrozole-induced PCOS via anti-inflammatory, antioxidant, anti-fibrotic, and angiogenesis regulating mechanisms. Its effects were almost comparable to metformin, and the combination of both has no further synergistic effect.

Additional file 1. Supplementary table 1. ROC curve analysis. Supplementary table 2. Cumulative OS and DFS.

Ovarian tumours are commonly seen in reproductive age group in women. However, when they occur at extremes of age, the suspicion of malignancy increases. The detection of dermoid cyst at 56 years of age is uncommon, hence proper imaging with CA-125 level monitoring is essential. Awareness of benign tumours or rare possibility of malignant transformation in such age is mandatory for surveillance management or planning the surgical procedure.

Development of a highly efficient and coke-resistant, nickel based nano-catalyst in the carbon dioxide reformation of methane is reported. The alumina supported Ni-based catalyst with a metal loading of 5wt% was prepared via the solution combustion synthesis (SCS) method as well as the conventional wetness impregnation method. The synthesized catalysts were thoroughly characterized by a combination of analytical techniques including high-resolution electron microscopy (HRTEM-SAED), X-ray diffraction (XRD), nitrogen physisorption (BET surface area), X-ray photoelectron spectroscopy (XPS), temperature programmed reduction (H 2 -TPR) and temperature programmed oxidation (TPO). Compared to the conventional nickel-impregnated (Ni-I) catalyst, the Ni-SCS nano-catalyst was superior in activity and stability during dry reformation of methane. Ni-SCS catalyst exhibited higher percentage conversions of methane and carbon dioxide. The percentage yields of hydrogen and carbon monoxide over Ni-SCS catalyst were also significantly higher. During the investigated period on stream for 50 h, the Ni-I catalyst deactivated severely, by contrast the Ni-SCS stayed active. It was clear from the results of elemental carbon analysis and TPO that deactivation of the Ni-I catalyst was due to severe carbon deposition, whereas the Ni-SCS catalyst exhibited minor carbon deposition. These differences in the catalytic activities and stabilities between the Ni-I and Ni-SCS catalysts were attributed to the difference in their physicochemical properties and chemical structure, as obvious from the results of the above mentioned analysis techniques. The XRD and XPS analysis revealed that the Ni-SCS nanocatalyst resulted in the formation of uniformly distributed nickel aluminates (NiAl 2 O 4 ) nano-crystallite spinels together with nickel oxide. The results of H 2 - TPR analysis clearly distinguished between NiO and NiAl 2 O 4 . H 2 -TPR affirmed the formation of NiAl 2 O 4 and NiO species on the SCS nanocatalyst but only NiO within the impregnation catalyst. In this regards the exceptionally high catalytic activity and stability of Ni-SCS nanocatalyst during dry reformation was attributed to the presence of NiAl 2 O 4 nano-crystallites structures. On the other hand, the presence of weakly associated NiO species on the Ni-I catalyst was responsible for decaying its activity due to carbon formation during the dry reformation of methane. This research work was made possible by the Qatar Shell Research and Technology Center (QSRTC) funded project QUEX-CENG-QSRTC-18/19 . Scopus

When managing coronavirus disease 2019 (COVID-19) patients, radiological imaging complements clinical evaluation and laboratory parameters. We aimed to assess the sensitivity of chest radiography findings in detecting COVID-19, describe those findings, and assess the association of positive chest radiography findings with clinical and laboratory findings. A multicentre, cross-sectional study was conducted involving all primary health care corporation-registered patients (2485 patients) enrolled over a 1-month period during the peak of the 2020 pandemic wave in Qatar. These patients had reverse transcription-polymerase chain reaction-confirmed COVID-19 and underwent chest radiography within 72 hours of the swab test. A positive result on reverse transcription-polymerase chain reaction was the gold standard for diagnosing COVID-19. The sensitivity of chest radiography was calculated. The airspace opacities were mostly distributed in the peripheral and lower lung zones, and most of the patients had bilateral involvement. Pleural effusion was detected in some cases. The risk of having positive chest X-ray findings increased with age, Southeast Asian nationality, fever, or a history of fever and diarrhoea. Patients with cardiac disease, obesity, hypertension, diabetes, and chronic kidney disease were at a higher risk of having positive chest X-ray findings. There was a statistically significant increase in the mean serum albumin, white blood cell count, neutrophil count, and serum C-reactive protein, hepatic enzymes, and total bilirubin with an increase in the radiographic severity score.

Uncertainty due to imprecise data and linguistically expressed information is inherent to real-life problems. Tactical production planning cannot neglect the presence of uncertainty due to the length of the planning horizon and the multitude of interacting factors affecting the manufacturing environment. Quantities expressed linguistically are best described by fuzzy sets to capture vagueness and to facilitate decision making in an uncertain context. This work considers developing an aggregate production plan with fuzzy demand and fuzzy cost elements. A fuzzy linear programming model is proposed that aims to minimize the total production costs and penalty costs caused by the unutilized capacity and unsatisfied demand. The proposed model is illustrated via a numerical example reflecting different cases that may occur in industry. The obtained results determine the optimum aggregate production plan while giving the decision-maker the flexibility to select the degree of satisfaction of constraints.

Background/purpose: Inguinoscrotal lesions (ISLs) are not uncommon during the first month of life. Most of the lesions are congenital. Although physical examination can detect most of the lesions, differential diagnosis is sometimes difficult. Our objective was to evaluate different patterns and spectrums of surgical causes of ISLs seen in the neonatal period.Patients and methods: This prospective observational study included neonates with surgical causes of ISL presented during the period from June 2015 to September 2016. Neonates with nonsurgical causes of ISL were excluded. All cases were subjected to management strategies that consist of physical examinations, imaging studies accordingly, and surgical repair, when needed. The approval of the ethics committee was obtained. Demographic data, presence of associated anomalies, operative data, and outcome of surgical intervention during neonatal period all were reported and analyzed.Results: There were 63 neonates with surgical causes of ISL. The spectrum of findings was as follows: 28 (44.4%) patients with hernia including complicated hernias, 18 (28.6%) patients with hydrocele, 12 (19%) patients with empty scrotum (unilateral or bilateral), three (4.8%) patients with scrotal anomalies, one patient with torsion, and one patient with hematoma.Conclusion: ISL in neonates carries a wide range of varieties. Although congenital inguinal hernia is the commonest, other causes should be kept in mind for differential diagnosis.Keywords: hydrocele, inguinoscrotal lesions, neonatal congenital inguinal hernia

Double ring infiltrometer is a simple device used to measure water infiltration rate in the soil, one of the most important hydro physical characteristics and an essential parameter for various applications including: surface irrigation and drainage projects, infiltration or water purification basins, seepage losses at canals, soil leaching at waste storage sites. However, the high spatial variability of a soil makes a single point measurement rarely representative of an entire field. Nonetheless, Double Ring Infiltration tests are tedious, time consuming and require continuous attention, hence limiting the number of tests that may be performed simultaneously on a given site. In the present research, an automated Internet of Things (IoT) double ring infiltrometer (DRI) is developed and validated in a loamy field. It consists of a DRI equipped with an ESP-32 microcontroller chip, a GPS module, a solenoid valve, a DIY conductance water level sensor, and a SD card module powered by a 12 V 11000mAh Li-ion battery charged by a 10 W solar panel. The double ring infiltrometer is designed to calculate the infiltration rate in real time, to store the data with the time stamp and geographical coordinates on an SD card or, to use a cloud service platform to upload the data over the internet. The aim is to facilitate soil infiltration mapping for precision agriculture and to build a soil infiltration inventory that could be used to continuously improve existing soil database. The system was assembled and tested at nine different locations on a loamy soil experimental field. For validation, conventional (manually operated) tests were conducted at the same time. The system proved to be reliable (R2 = 0.99), cost effective (115$) and a hassle-free solution, ideal for multiple soil infiltration measurements.

Development of a highly efficient and coke-resistant, nickel nanoparticles (Ni.NPs) based catalyst in the steam reformation reaction of methane is reported. The catalyst was prepared by dispersing Ni-nanoparticles over silica functionalized alumina support. The synthesized samples were characterized by a combination of analytical techniques of X-ray diffraction (XRD), nitrogen physisorption (BET surface area), X-ray photoelectron spectroscopy (XPS), temperature programmed reduction (H2-TPR) and temperature programmed oxidation (TPO).Characterization results revealed that functionalization of alumina resulted in improved physicochemical properties of Ni-nanoparticles catalyst compared to the conventional nickel based catalysts. More importantly, a clear improvement on the catalytic hydrogen production and resistance to coke was observed. At all temperature studied Ni.NPs catalyst exhibited high methane conversions which reached to 100% at 750 °C. Also, the Ni.NPs catalysts exhibited high H2 selectivity and excellent thermal stability.The functionalization of alumina with silica improved the dispersion of Ni nanoparticles and prevented sintering and aggregation. Ni.NPs catalyst exhibited stable catalytic activities for a period of 48 h where no carbon deposition was evidenced neither by TPO nor XPS techniques. Contrary to Ni.NPs the conventional nickel catalyst suffered from severe deactivation due to deposition of filamentous carbon on the surface. This paper was made possible by a NPRP Grant #6-290-1-059 From the Qatar National Research Fund (a member of Qatar Foundation).

In this study, the sorption behavior of synthetic (Analcime) zeolites with respect to nitrate ions has been studied in order to consider its application to purity ground water. Analcime or also can be called analcite (“weak”) is a kind of grey, white or colorless tectosilicates minerals. It is hydrated sodium aluminum silicates which exist in cubic form in crystalline. Analcime was successively synthesized from kaolinite as a raw material using the fusion with NaOH method. The conditions of hydrothermal crystallization (zeolitization) were found to be at temperature of 170 C˚, and time span between 36 h and 72 h for kaoline with the molar composition of 6Na2O: 0.75Al2O3:30SiO2. 780H2O.The synthetic materials have been characterized by X-ray diffraction (XRD), scanning electron microscope (SEM), Fourier transform infrared spectroscopy (FT-IR), thermo gravimetric (DTA/TGA) analysis and Surface area and porosity of synthesized analcime .The results indicate that the crystallization of analcime not affected by the hydrothermal reaction time. Also analcime was tested as adsorbents for the removal of nitrate ions from the ground water samples from Wadi El-Assiuti – Egypt .The adsorption capacities of nitrate ions by analcime, as a function of its concentration, were determined at room temperature by varying analcime concentration for each water samples. During the process, all the other parameters (pH and contact time) were kept constant with respect to the initial concentration of nitrate ions in the water samples. It was found analcime has good removal efficiency obtained at pH 6-7.6, adsorbent dosage 10-12 g/L, and contact time 60 min. The Langmuir constants model for NO3 − ion sorption on the adsorption isotherms is fitted well. The RL value in the present investigation was equal or less than one, indicating that the adsorption of NO3 −ion by analcime is favorable.

Purpose The objective of this study was to determine if there is a dose-response relationship between sulfonylureas and major adverse cardiovascular events (MACE). Methods We conducted a retrospective cohort study among elderly patients with no history of acute coronary syndrome or stroke who initiated gliclazide or glyburide therapy between 1998 and 2010. Gliclazide and glyburide users were evaluated separately, and a high-dimensional propensity score (HDPS) was used to match patients initiating therapy with a low or high dose. A time-dependent variable was used to further characterize exposure, which can change during follow-up. Cox proportional hazard regression models were used to compare the risk of MACE between low (reference) and high doses. Results We identified 14,213 new users of gliclazide or glyburide (mean age, 74.7 (standard deviation 6.4) years; males, 52.8%; and mean follow-up duration, 2.7 (standard deviation 2.9) years). Among gliclazide users, there was a higher risk of MACE with high compared with low dose (crude rates: 32.8 and 28.2 per 1000 person-years, respectively), but this did not reach statistical significance (HDPS-matched hazard ratio) 1.15; 95% confidence interval (0.96–1.38). For glyburide users, however, MACE occurred more frequently in the high compared with low dose (crude rates: 38.9 and 31.5 per 1000 person-years, respectively; HDPS-matched hazard ratio 1.24; 95% confidence interval 1.02–1.50). Conclusions Among new users of sulfonylureas, there appears to be a dose-response relationship between glyburide and MACE, but not for gliclazide. Copyright © 2016 John Wiley & Sons, Ltd.

Background Animal models have demonstrated that sulfonylureas increase the size of myocardial infarction; however, data in humans is scarce. This study evaluated the association between sulfonylurea use and infarct size in diabetes patients with ST-elevation myocardial infarction (STEMI). Methods Consecutive STEMI patients admitted in Edmonton, Canada between 2006 and 2011 were enrolled in a regional prospective registry program. Patients with type 2 diabetes were identified from this group and the maximum recorded troponin I (max cTnI) within the first 48h of chest pain onset was used as the primary outcome to quantify infarct size. The relationship between preadmission sulfonylurea use and max cTnI was assessed using multivariable linear regression to adjust for patient demographics, cardiovascular risk factors, clinical data on admission, ischemia time, reperfusion therapy and preadmission drugs. Results There were 560 STEMI patients with type 2 diabetes; mean (standard deviation; SD) age was 63.3 (12.8) years, 395 (70.5%) were male, 216 (38.6%) received primary percutaneous intervention, and 211 (37.7%) received thrombolysis. The max cTnI was higher in 146 sulfonylurea users compared to 414 non-sulfonylurea users (mean (SD): 49.8 (74.3) ng/mL versus 39.9 (50.4) ng/mL, respectively; adjusted between-group difference: 12.9ng/mL; 95% CI 0.3–25.5; p=0.044). Conclusion This study adds further evidence to the proposed causal relationship between sulfonylureas and adverse cardiovascular events by observing a significant difference in infarct size among type 2 diabetes patients presenting with STEMI. Clinicians should consider this association when prescribing sulfonylureas to manage patients with type 2 diabetes.

In this paper, a comparative investigation of the catalytic performances of Pd@TiO2 and Pd@CeO2, core-shells nanocatalysts supported over functionalized alumina, for application to methane oxidation is presented. The results indicated that the Pd@CeO2/SiO2.Al2O3 core-shell nanocatalyst exhibited higher activity and stability than the Pd@TiO2/SiO2.Al2O3 nanocatalyst. Complete combustion of methane over the Pd@CeO2/SiO2.Al2O3 nanocatalyst was achieved at about 400 °C. By contrast, the maximum combustion of methane over the Pd@TiO2/SiO2.Al2O3 nanocatalyst was only attained at ∼550 °C. The Pd@TiO2/SiO2.Al2O3 nanocatalyst experienced deactivation, and a transient dip in methane conversion in the temperature region between 580 °C and 750 °C was also observed. The exceptional activity of the Pd@CeO2/SiO2.Al2O3 nanocatalyst was attributed to the intimate interaction between palladium (Pd) and ceria (CeO2) and efficient oxygen back-spillover at Pd and CeO2 interface resulting from the core-shell structure. This paper was made possible by an NPRP Grant # 6-290-1-059 from the Qatar National Research Fund (a member of Qatar Foundation). The statements made herein are solely the responsibility of the authors. Scopus

Development of a highly efficient, nickel-based nano-catalyst in the carbon dioxide reformation of methane is reported. The alumina supported Ni-based catalyst with a metal loading of 5wt% was prepared via solution combustion synthesis (SCS) method and conventional wetness impregnation method. Compared to that of conventional Ni(I) catalyst, the Ni(SCS) catalyst exhibited high activity for methane conversion and superior selectivity for H 2 and CO production during dry reforming of methane. This difference in the catalytical performances of both catalysts during the dry reformation of methane was attributed to difference in morphology and chemical structures of the catalysts. The HAADF-EDS analysis of the Ni(SCS)catalyst revealed Ni was homogeneously distributed over the substrate with an average particle size of 7±2.31nm. Additionally, SAED patterns suggested that nickel was mainly observed in the NiAl 2 O 4 phase. These findings were affirmed by the XRD analysis. By contrast the Ni(I) catalyst revealed the presence of free NiO species only. Scopus

Background: Hypospadias is one of the most common congenital anomalies, occurring in Bone of 200 to one of 300 live births. Tubularized incised plate (TIP) urethroplasty or the Snodgrass procedure has gained worldwide acceptance for distal hypospadias repair because of its low complication rate and technical simplicity. Objective: We compared two refinements in TIP repair for primary distal hypospadias, namely, a subcuticular uninterrupted suturing technique and full-thickness interrupted sutures. In addition, we compared the impact of these surgical modifications on the complication rate and surgical outcome of the Snodgrass procedure. Patients and methods: Eighty boys with primary distal hypospadias were treated using the TIP procedure between January 2009 and December 2011. Patients were prospectively randomized into two equal groups on the basis of the suturing technique. A neourethra was constructed using a subcuticular uninterrupted suturing technique (group A) or using full-thickness interrupted sutures (group B). All patients were subjected to the same preoperative, operative, and follow-up protocols. Both groups were compared as regards the complication rate. Results: The age ranged between 8 and 48 months, with a mean age of 13.6 ± 6.9 months at the time of repair. The overall success rate was 90% (97.5% for group A and 82.5% for group B). Late complications in the form of a urethrocutaneous fistula, meatal stenosis, and wound dehiscence or infection developed in eight (10%) patients (one patient of group A and seven of group B). The mean follow-up duration was 8.1 ± 2.4 months (range 4–13 months). Conclusion: The subcuticular uninterrupted suturing technique seems to have a lower complication rate when compared with the use of full-thickness interrupted sutures in the repair of distal hypospadias by TIP urethroplasty. Keywords: Hypospadias, Tubularized Incised Plate, Urethroplasty

Hemodialysis (HD) catheter dysfunction compromises HD adequacy and increases the cost of patient care. Repeated administration of alteplase in HD catheters typically produces only short-term benefits. The purpose of this study was to design, implement, and evaluate the efficacy of an experimental alteplase algorithm to manage HD catheter dysfunction. This was a two-part prospective nonrandomized study. Baseline data of alteplase use and catheter exchange were collected during part 1 of the study. Part 2 consisted of the alteplase algorithm implementation and repeat collection of catheter data. Rates of alteplase use and catheter exchange per 1000 catheter-days were the primary and secondary outcomes of the study. One hundred and seventy-two catheters in 131 patients were followed prospectively during the course of the study. The adjusted relative rate (RR) of alteplase use showed no significant difference between both parts of the study, adjusted RR: 1.10, 95% confidence interval (CI) (0.73-1.65). Similarly, catheter exchange rates were not significantly different over the duration of the study (1.12 vs. 1.03 per 1000 catheter-days). However, waiting time for catheter exchange increased from 20.36 ± 14 days in part 1 to 38.42 ± 28 days in part 2 (P < 0.05). The alteplase algorithm did not significantly reduce alteplase use. This may be partially explained by repeated use of alteplase in part 2, due to longer waiting times for catheter exchange procedures.

We report on the synthesis and testing of active and stable nano-catalysts for methane oxidation. The nano-catalyst was palladium/ceria supported on alumina prepared via a one-step solution-combustion synthesis (SCS) method. As confirmed by X-ray photoelectron spectroscopy (XPS) and high-resolution transmission electron microscopy (HTEM), SCS preparative methodology resulted in segregating both Pd and Ce on the surface of the Al 2 O 3 support. Furthermore, HTEM showed that bigger Pd particles (5 nm and more) were surrounded by CeO 2 , resembling a core shell structure, while smaller Pd particles (1 nm and less) were not associated with CeO 2 . The intimate Pd-CeO 2 attachment resulted in insertion of Pd ions into the ceria lattice, and associated with the reduction of Ce 4+ into Ce 3+ ions; consequently, the formation of oxygen vacancies. XPS showed also that Pd had three oxidation states corresponding to Pd0, Pd 2+ due to PdO, and highly ionized Pd ions (Pd (2+x)+ ) which might originate from the insertion of Pd ions into the ceria lattice. The formation of intrinsic Ce 3+ ions, highly ionized (Pd2+ species inserted into the lattice of CeO 2 ) Pd ions (Pd (2+x)+ ) and oxygen vacancies is suggested to play a major role in the unique catalytic activity. The results indicated that the Pd-SCS nano-catalysts were exceptionally more active and stable than conventional catalysts. Under similar reaction conditions, the methane combustion rate over the SCS catalyst was ~18 times greater than that of conventional catalysts. Full methane conversions over the SCS catalysts occurred at around 400 C but were not shown at all with conventional catalysts. In addition, contrary to the conventional catalysts, the SCS catalysts exhibited superior activity with no sign of deactivation in the temperature range between ~400 and 800 C. 2018 by the authors. Licensee MDPI, Basel, Switzerland. Acknowledgments: This paper was made possible by an NPRP Grant #6-290-1-059 from the Qatar National Research Fund (a member of Qatar Foundation). The statements made herein are solely the responsibility of the authors. Scopus

Pipelines require periodical inspection to detect corrosion, deformation and congestion with obstacles in the network. Autonomous mobile robots are good solutions for this task. Visual information from the pipe interior associated with a location stamp is needed for inspection. In this paper, the previous designs of autonomous robots are reviewed and a new robot is developed to ensure simple design and smooth motion. Images are processed online to detect irregularity in pipe and then start capturing high resolution pictures to conserve the limited memory size. The new robot moves in pipes and provides video stream of pipe interior with location stamp. The visual information can later be processed offline to extract more information of pipeline condition to make maintenance decisions.

Objective: To compare between two methods of surgical treatment for fistula-in-ano (FIA) in infants, fistulotomy and fistulectomy, and their surgical outcome and also to review the clinical presentation and diagnosis of this condition in our tertiary center. Background: FIA occurring in infants is a relatively common condition. It is more common in boys than in girls, and 96% of cases occur in infants younger than 1 year. The surgical treatment options of these fistulas are fistulotomy or fistulectomy. Patients and methods : In this study, between January 2010 and December 2011, 36 infants with low-type FIA were treated surgically. Eighteen infants were treated by fistulotomy (group A) and 18 were treated by fistulectomy (group B). No infant had underlying illness. All cases were subjected to the same protocol of preoperative evaluation, anesthesia, and follow-up protocol. The two techniques were compared in terms of the operative time, healing time, complications, and outcome. All were reported, analyzed, and compared. Results: Male sex predominance was reported. Twentyseven infants were younger than 1 year old and the remaining patients were in their second year of life, with a mean age of 9.7± 4.9 months. The mean values of healing time were 21± 3.01 days for group A (range 17–28 days) and 26.6 ± 1.42 days for group B (range 25–30 days). There was a statistically significant difference between the two groups in both the operative time and the healing time. There was one recurrence and one granuloma in group B. One wound infection was reported in patients who underwent fistulotomy (group A). Conclusion: The treatment of FIA in infants remains controversial and it can be treated either by fistulotomy or by fistulectomy. However, there are fewer risks and shorter recovery times associated with fistulotomy as compared with fistulectomy. A future study involving nonoperative management would be required to assess other treatment options. Keywords: Fistula-in-ano, Fistulectomy, Fistulotomy

The objective of this study was to determine if there is a dose-response relationship between sulfonylureas and major adverse cardiovascular events (MACE).We conducted a retrospective cohort study among elderly patients with no history of acute coronary syndrome or stroke who initiated gliclazide or glyburide therapy between 1998 and 2010. Gliclazide and glyburide users were evaluated separately, and a high-dimensional propensity score (HDPS) was used to match patients initiating therapy with a low or high dose. A time-dependent variable was used to further characterize exposure, which can change during follow-up. Cox proportional hazard regression models were used to compare the risk of MACE between low (reference) and high doses.We identified 14,213 new users of gliclazide or glyburide (mean age, 74.7 (standard deviation 6.4) years; males, 52.8%; and mean follow-up duration, 2.7 (standard deviation 2.9) years). Among gliclazide users, there was a higher risk of MACE with high compared with low dose (crude rates: 32.8 and 28.2 per 1000 person-years, respectively), but this did not reach statistical significance (HDPS-matched hazard ratio) 1.15; 95% confidence interval (0.96-1.38). For glyburide users, however, MACE occurred more frequently in the high compared with low dose (crude rates: 38.9 and 31.5 per 1000 person-years, respectively; HDPS-matched hazard ratio 1.24; 95% confidence interval 1.02-1.50).Among new users of sulfonylureas, there appears to be a dose-response relationship between glyburide and MACE, but not for gliclazide. Copyright © 2016 John WileySons, Ltd.

Summary Background Sulfonylureas are common second-line options for management of type 2 diabetes; however, they are associated with a higher risk of cardiovascular events compared with other antidiabetic drugs. Since tissue selectivity and risk of hypoglycaemia differ among sulfonylureas, we aimed to assess whether mortality and the risk of cardiovascular events also varies. Methods We searched Medline and Embase from inception to June 11, 2014, to identify controlled studies reporting the risk of all-cause mortality, cardiovascular-related mortality, or myocardial infarction for at least two sulfonylureas. We examined differences in cardiovascular event risk among sulfonylureas with random effects models for direct pairwise comparisons and network meta-analyses to incorporate direct and indirect data. Findings 14 970 (9%) of 167 327 patients in 18 studies died: 841 (4%) of 19 334 gliclazide users, 5482 (11%) of 49 389 glimepiride users, 2106 (15%) of 14 464 glipizide users, 5296 (7%) of 77 169 glibenclamide users, 1066 (17%) of 6187 tolbutamide users, and 179 (23%) of 784 chlorpropamide users. Inconsistency was low for the network meta-analysis of all-cause mortality, and the relative risk of death compared with glibenclamide was 0·65 (95% credible interval 0·53–0·79) for gliclazide, 0·83 (0·68–1·00) for glimepiride, 0·98 (0·80–1·19) for glipizide, 1·13 (0·90–1·42) for tolbutamide, and 1·34 (0·98–1·86) for chlorpropamide. Similar associations were noted for cardiovascular-related mortality: the relative risk compared with glibenclamide was 0·60 (95% credible interval 0·45–0·84) for gliclazide, 0·79 (0·57–1·11) for glimepiride, 1·01 (0·72–1·43) for glipizide, 1·11 (0·79–1·55) for tolbutamide, and 1·45 (0·88–2·44) for chlorpropamide. Interpretation Gliclazide and glimepiride were associated with a lower risk of all-cause and cardiovascular-related mortality compared with glibenclamide. Clinicians should consider possible differences in risk of mortality when selecting a sulfonylurea. Funding None.

More than 40 years after publication of the University Group Diabetes Program trial, the cardiovascular safety of sulphonylureas is still contentious. Although several hypotheses linking sulphonylureas to adverse cardiovascular effects exist, none provide conclusive evidence. Adding to the controversy, current clinical trials and observational studies provide inconsistent, and sometimes conflicting, evidence for the cardiovascular effects of sulphonylureas. Overall, observational evidence suggests that an increased risk of adverse cardiovascular outcomes is associated with sulphonylureas; however, these data may be subject to residual confounding and bias. Although evidence from randomized controlled trials has suggested a neutral effect, the majority of these studies were not specifically designed to assess the effect of sulphonylureas on adverse cardiovascular event risk. Current ongoing large clinical trials may provide some clarity on the cardiovascular safety of sulphonylureas, but the results are not expected for several years. With the continued uncertainties concerning the cardiovascular safety of all antidiabetic drugs, a clear answer with regard to sulphonylureas is warranted. The objectives of the present article were to provide an overview of the controversy surrounding sulphonylurea-related cardiovascular effects, to discuss the limitations of the current literature, and to provide recommendations for future studies aiming to elucidate the true relationship between sulphonylureas and adverse cardiovascular effects in people with type 2 diabetes.

Aim To evaluate the association between insulin secretagogues and adverse cardiovascular sequelae in type 2 diabetes patients hospitalized for ischemic heart disease (IHD). Methods Administrative health records from Alberta, Canada between 1998 and 2010 were used to identify 2,254 gliclazide, 3,289 glyburide and 740 repaglinide users prior to an IHD-related hospitalization. Multivariable Cox regression models were used to compare the 30-day risk of a composite outcome of all-cause mortality or new onset of atrial fibrillation, stroke, heart failure or myocardial infarction according to insulin secretagogue use. Results Mean (SD) age was 76.1 (6.9) years, and 60.7% were men. The composite outcome occurred in 322 (30.2%) gliclazide users, 455 (28.1%) glyburide users and 81 (23.4%) repaglinide users within 30days of IHD hospitalization. There were no differences in risk for glyburide use (adjusted hazard ratio [aHR] 0.91; 95% confidence interval [CI] 0.78–1.05) or repaglinide use (aHR 0.80; 95% CI 0.63–1.03) compared to gliclazide. Similar results were observed in analyses for each element of the composite outcome. Conclusions In older patients with type 2 diabetes hospitalized for IHD, prior use of gliclazide, glyburide, or repaglinide appears to be associated with a similar risk of adverse cardiovascular sequelae.

Aim Sulfonylureas might increase the risk of adverse cardiovascular events; however, emerging evidence suggests there may be important differences amongst these drugs. Some, like glyburide, inhibit KATP channels in the heart and pancreas, while others, like gliclazide, are more likely to selectively inhibit KATP channels in the pancreas. We hypothesized that the risk of acute coronary syndrome (ACS) events would be higher in patients using glyburide compared with gliclazide. Methods This nested case–control study used administrative health data from Alberta, Canada. New users of glyburide or gliclazide aged ≥66 years between 1998 and 2010 were included. Cases were individuals with an ACS-related hospitalization or death. Up to four controls were matched based on birth year, sex, cohort-entry year and follow-up time. Multivariable conditional logistic regression was used to estimate adjusted odds ratios (OR), controlling for baseline drug use and co-morbidities. Results Our cohort included 7441 gliclazide and 13 884 glyburide users; 51.4% men, mean (s.d.) age 75.5 (6.6) years and mean (s.d.) duration of follow-up 5.5 (4.0) years. A total of 4239 patients had an ACS-related hospitalization or death and were matched to 16 723 controls. Compared with gliclazide use, glyburide use was associated with a higher risk (adjusted OR 1.14; 95% CI 1.06–1.23) of ACS-related hospitalization or death over 5.5 years (number needed to harm: 50). Conclusion In this observational study, glyburide use was associated with a 14% higher risk of ACS events compared with gliclazide use. Although the difference is small and probably to have implications at the population level rather than the individual patient or clinician, any causal inferences regarding sulfonylurea use and adverse cardiovascular risk should be tested in a large-scale randomized controlled trial.

To describe the use patterns of metformin-based antidiabetic regimens in patients with type 2 diabetes and to identify predictors of initiating metformin monotherapy.By using administrative databases from Alberta, Canada, we identified all metformin users ages 65 years and older between 1998 and 2010. Rates of metformin use, either alone or in combination with other antidiabetic drugs, were evaluated at 6-month intervals. All rates were direct age- and sex-standardized using the 2006 Alberta census. Trends over time were assessed using Joinpoint regression software (National Cancer Institute, USA). In addition, a cohort of new users of antidiabetic drugs was identified and multivariable logistic regression models were constructed to identify independent predictors of receiving initial treatment with metformin monotherapy.Metformin monotherapy became the most common metformin-based regimen (508 of 1000 persons in 2010). Sulfonylureas were the most prevalent add-on drug to metformin; however, their use significantly decreased from 548 of 1000 in 1998 to 182 of 1000 persons in 2010 (67% reduction; p0.001), with more patients using newer drugs, mainly thiazolidinediones (103 of 1000 persons in 2007). Combination therapy of metformin with glinides or insulin also significantly increased during the same period. Compared with patients starting sulfonylurea monotherapy, patients starting metformin monotherapy were younger, had fewer cardiovascular complications and lower healthcare use rates.In accordance with the clinical practice guidelines, patients with type 2 diabetes manage hyperglycemia mainly with metformin monotherapy and sulfonylureas are the most common add-on therapy. Older age and the presence of nephropathy, liver disease or congestive heart failure were important predictors for starting sulfonylurea monotherapy rather than metformin monotherapy.

Hemodialysis (HD) catheter dysfunction compromises HD adequacy and increases the cost of patient care. Repeated administration of alteplase in HD catheters typically produces only short-term benefits. The purpose of this study was to design, implement, and evaluate the efficacy of an experimental alteplase algorithm to manage HD catheter dysfunction. This was a two-part prospective nonrandomized study. Baseline data of alteplase use and catheter exchange were collected during part 1 of the study. Part 2 consisted of the alteplase algorithm implementation and repeat collection of catheter data. Rates of alteplase use and catheter exchange per 1000 catheter-days were the primary and secondary outcomes of the study. One hundred and seventy-two catheters in 131 patients were followed prospectively during the course of the study. The adjusted relative rate (RR) of alteplase use showed no significant difference between both parts of the study, adjusted RR: 1.10, 95% confidence interval (CI) (0.73-1.65). Similarly, catheter exchange rates were not significantly different over the duration of the study (1.12 vs. 1.03 per 1000 catheter-days). However, waiting time for catheter exchange increased from 20.36 ± 14 days in part 1 to 38.42 ± 28 days in part 2 (P0.05). The alteplase algorithm did not significantly reduce alteplase use. This may be partially explained by repeated use of alteplase in part 2, due to longer waiting times for catheter exchange procedures.

Aim Insulin secretagogues promote insulin release by binding to sulfonylurea receptors on pancreatic β-cells (SUR1). However, these drugs also bind to receptor isoforms on cardiac myocytes (SUR2A) and vascular smooth muscle (SUR2B). Binding to SUR2A/SUR2B may inhibit ischaemic preconditioning, an endogenous protective mechanism enabling cardiac tissue to survive periods of ischaemia. This study was designed to identify insulin secretagogues that selectively bind to SUR1 when given at therapeutic doses. Methods Using accepted systematic review methods, three electronic databases were searched from inception to 13 June 2011. Original studies measuring the half-maximal inhibitory concentration (IC(50)) for an insulin secretagogue on K(ATP) channels using standard electrophysiological techniques were included. Steady-state concentrations (C(SS)) were estimated from the usual oral dose and clearance values for each drug. Results Data were extracted from 27 studies meeting all inclusion criteria. IC(50) values for SUR1 were below those for SUR2A/SUR2B for all insulin secretagogues and addition of C(SS) values identified three distinct patterns. The C(SS) for gliclazide, glipizide, mitiglinide and nateglinide lie between IC(50) values for SUR1 and SUR2A/SUR2B, suggesting that these drugs bind selectively to pancreatic receptors. The C(SS) for glimepiride and glyburide (glibenclamide) was above IC(50) values for all three isoforms, suggesting these drugs are non-selective. Tolbutamide and repaglinide may have partial pancreatic receptor selectivity because IC(50) values for SUR1 and SUR2A/SUR2B overlapped somewhat, with the C(SS) in the midst of these values. Conclusions Insulin secretagogues display different tissue selectivity characteristics at therapeutic doses. This may translate into different levels of cardiovascular risk.

Delineation of structure and dynamics of proteins is a prerequisite for comprehension of their biochemical roles 'in vivo'. The 'structure-function' paradigm has been refined by the realization that a significant fraction of eukaryotic proteins have substantial disordered regions, yet are involved in critical processes within the cell. The members of myelin basic protein family (MBP) are identified as being intrinsically disordered, and participate in a diversity of important roles in the central nervous system. This thesis is devoted to the investigation of the structure and dynamics of different members of the MBP family. Solution NMR spectroscopy was used to achieve sequence-specific resonance assignments of the rmBG21 golli isoform of MBP. Chemical shift indexing revealed few small fragments having tendency towards [alpha]-helicity, which may represent putative recognition motifs. Backbone dynamics extracted from 15N spin relaxation confirmed the intrinsic disordered nature of the protein. The N-terminal golli-specific portion (residues S5--T69) and the glycine-rich segment Al26--G129 were exceptionally flexible. The N-terminal region may provide additional plasticity, or conformational adaptability, in protein-protein interactions, while the A126-G129 region may function as a hinge. SSNMR and FTIR spectroscopy were used to delineate structural propensities and dynamics of the classic 18.5 kDa isoform of MBP in association with actin microfilaments. FTIR showed induced folding of both protein partners: increase in [beta]-sheet content of actin and increases in both [alpha]-helix and [beta]-sheet content of MBP. SSNMR specifically located these elements in the terminal fragments of MBP, and in a central immunodominant epitope. SSNMR was utilised to achieve a comparative study of the central immunodominant epitope of the recombinant murine MBP C1 mimic (rmC1) and its deiminated C8 mimic (rmC8) in association with model membranes. Our measurements showed that the epitope adopted [alpha]-helical conformation in both protein variants (albeit with shorter length than was previously reported) and that the helix was less motionally restricted (as a result of its cytoplasmic exposure) in rmC8 compared to rmC1. Our studies as a whole have revealed that MBP is conformationally polymorphic, a structural state that is in consistence with its roles as a linker and signalling hub.

Background Randomized controlled trials have shown that ≤100 mg aspirin daily is not effective for primary prevention of cardiovascular events in diabetes; however, clinical and pharmacologic evidence suggests these patients need >100 mg for adequate antiplatelet activity. Although high on-treatment platelet reactivity (HTPR) could explain the lack of benefit, prevalence of HTPR in diabetes is not known. This systematic review examined the relationship between daily aspirin dose and prevalence of HTPR in patients with diabetes. Methods Three electronic databases were searched until May 2013 using database-appropriate terms for aspirin, resistance, and diabetes. Studies were included if prevalence of HTPR was reported according to daily dose and diabetes status. Patients were stratified by daily aspirin dose and the weighted mean prevalence across studies was calculated. Where appropriate, pooled relative risks (RR) were calculated using a random-effects model. Results Data were available from 31 studies that enrolled 2147 diabetic patients. Overall, prevalence of HTPR was 21.9% (95% confidence interval [CI], 15.2%-28.5%) in diabetic patients and 15.8% (95% CI, 11.4%-20.3%) in nondiabetic patients (pooled RR 1.36; 95% CI, 1.08-1.71; I 2 56%). Prevalence appeared to be dose related, with 398 (23.6%) of 1689 diabetic patients using ≤100 mg daily having HTPR compared with 64 (12.3%) of 518 diabetic patients using 101-325 mg daily (pooled RR 1.70; 95% CI, 1.07-2.72; I 2 0%). Conclusions Although these observations should be verified in a clinical trial, the possibility that 1 in 4 patients have HTPR with doses commonly used in diabetes could have significant implications on overall effectiveness of aspirin.