7 +/- 1.9 weeks. selleck compound Baclofen was started at a postnatal age of 86.4 +/- 33.6 days. Comparison of Modified Ashworth Scale scores after initiation

of therapy to prebaclofen scores demonstrated no significant decrease in muscle tone. Results of our study show that there is no overall decrease in tone during oral baclofen therapy in hypertonic preterm neonates.”
“Strawberry (Fragariaxananassa Duch), a fruit of economic and nutritional importance, is also a model species for fleshy fruits and genomics in Rosaceae. Strawberry fruit quality at different harvest stages is a function of the fruit’s metabolite content, which results from physiological changes during fruit growth and ripening. In order to investigate strawberry fruit find more development, untargeted (GC-MS) and targeted (HPLC) metabolic profiling analyses were conducted. Principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) were employed to explore the non-polar and polar metabolite profiles from fruit samples at seven developmental stages. Different cluster patterns and a broad range of metabolites that exerted influence on cluster formation of metabolite profiles were observed. Significant changes in metabolite

levels were found in both fruits turning red and fruits over-ripening in comparison with red-ripening fruits. The levels of free amino acids decreased gradually before the red-ripening stage, but increased significantly in the over-ripening stage. Metabolite correlation and network analysis revealed the interdependencies of individual 17DMAG manufacturer metabolites and metabolic pathways. Activities of several metabolic pathways, including ester biosynthesis, the tricarboxylic acid cycle, the shikimate pathway, and amino acid metabolism, shifted during fruit growth and ripening. These results not only confirmed published metabolic data but also revealed new insights

into strawberry fruit composition and metabolite changes, thus demonstrating the value of metabolomics as a functional genomics tool in characterizing the mechanism of fruit quality formation, a key developmental stage in most economically important fruit crops.”
“We demonstrate a procedure for measuring the thermal conductivity of non-ideal thin-films with significant non-uniformity. By spatially mapping the thermal transport with time-domain thermoreflectance measurements, followed by statistical analysis, we determined the thermal conductivity of Cu composite films containing dispersed carbon nanotubes (CNTs). The thermal conductivity of the composite decreased from 188 to 60 W/m K as 1.8 wt. % of multi-walled CNTs was incorporated into nanocrystalline Cu. We compared the decreasing trend with that calculated from a scattering model to find out that the CNTs scatter the heat carriers in Cu. (C) 2011 American Institute of Physics. [doi:10.1063/1.

The effect of carbohydrates, however, may depend on the type consumed.

Objectives: By using substitution models, we aimed to investigate the risk of myocardial infarction (MI) associated

with a higher energy intake from carbohydrates and a concomitant lower energy intake from SFAs. Carbohydrates with different glycemic index (GI) values were also investigated.

Design: Our prospective cohort study NSC23766 mouse included 53,644 women and men free of MI at baseline.

Results: During a median of 12 y of follow-up, 1943 incident MI cases occurred. There was a nonsignificant inverse association between substitution of carbohydrates with low-GI values for SFAs and risk of MI [hazard ratio (HR) for MI per 5% increment of energy intake from carbohydrates: 0.88; 95% CI: 0.72, 1.07). In contrast, there was a statistically significant positive association between substitution of carbohydrates with high-GI values for

SFAs and risk of MI (HR: 1.33; 95% CI: 1.08, 1.64). There was no association for carbohydrates with medium-GI values (FIR: 0.98; 95% CI: 0.80, 1.21). No effect modification by Fludarabine sex was observed.

Conclusion: This study suggests that replacing SFAs with carbohydrates with low-GI values is associated with a lower risk of MI, whereas replacing SFAs with carbohydrates with high-GI values is associated with a higher risk of MI. J Clin Nutr 2010;91: 1764-8.”
“Introduction and hypothesis Antimuscarinic agents appear to exert their therapeutic activity in overactive bladder (OAB) via blockade of the M(3) muscarinic receptor subtype. Antimuscarinics are broadly similar in efficacy, but their safety and tolerability profiles vary, which may reflect differences in muscarinic receptor selectivity profiles.

Methods This review of available literature aims to determine whether antimuscarinic

agents with greater M3 selectivity have clinical advantages over less selective drugs.

Results Antimuscarinic agents differ widely in their propensity to cause cognitive and cardiovascular (CV) effects, which appear mainly to be related to differences in their relative selectivity for binding to non-M(3) receptors, including M(1) receptors in the brain and cardiac M(2) receptors.

Conclusions Cognitive and CV effects are especially pertinent for the OAB patient who tends to be older with various buy LY411575 comorbidities and is often taking multiple medications. Hence, it is important to consider the risk/benefit balance of antimuscarinic agents when selecting OAB treatment.”
“Background: It is generally agreed that in high transmission areas, pregnant women have acquired a partial immunity to malaria and when infected they present few or no symptoms. However, longitudinal cohort studies investigating the clinical presentation of malaria infection in pregnant women in stable endemic areas are lacking, and the few studies exploring this issue are unconclusive.

However, the crystallization mechanism of PCL does not change despite crystallization temperature and the addition of TA. The spherulitic growth rates of PCL also decrease with increasing crystallization temperature for both neat PCL and the PCL/TA blend; moreover, blending with TA reduces the spherulitic growth rate of PCL in the PCL/TA

blend. NSC-23766 It is also found that the crystal structure of PCL is not modified in the PCL/TA blend. (c) 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011″
“Purpose: To estimate the relative yield of therapeutic flexible sigmoidoscopy compared with complete optical colonoscopy for isolated left-sided polyps (>= 6 mm in diameter) identified

at screening computed tomographic (CT) colonography.

Materials and Methods: This retrospective institutional review board-approved and HIPAA-compliant study included a review of CT colonographic screening results in 6570 consecutive asymptomatic adults (3551 women, 3019 men; mean age, 56.8 years +/- 7.3 [standard deviation]). Of 887 (13.5%) patients with cases positive for nondiminutive polyps (>= 6 mm), a subset of 171 patients met the inclusion criteria (a) of having left-sided-only lesions of 6 mm or larger identified at CT colonography (rectum-to-splenic flexure) and (b) of undergoing subsequent evaluation with complete optical colonoscopy. CT colonography-optical colonoscopy concordance and https://www.selleckchem.com/products/AZD8931.html proximal-versus-distal diagnostic yield at optical colonoscopy were assessed. The 95% confidence intervals (CIs) were calculated for relevant results.

Results: From the study group of 171 patients, a total of 234 left-sided lesions of 6 mm or

larger were prospectively reported at CT colonography, of which 222 (94.9%; 95% CI: 91.3%, 97.0%) were confirmed as true-positive findings at optical colonoscopy. With optical colonoscopy, an additional 17 benign left-sided polyps of 6 mm or larger (13 small, four large) were found in 11 patients, resulting in a total left-sided yield of 239 nondiminutive lesions, including 137 small polyps (6-9 mm) and www.selleckchem.com/products/rocilinostat-acy-1215.html 102 large lesions (>= 10 mm), 160 neoplasms, 82 advanced adenomas, and seven cancers. Evaluation of the colon proximal to the splenic flexure in this cohort yielded eight small and two large benign polyps in nine patients but no proximal cancers or histologically advanced lesions.

Conclusion: For patients with left-sided-only polyps detected at CT colonography, the additional yield of complete optical colonoscopy beyond the expected reach of flexible sigmoidoscopy is very low and may not justify the added costs, potential risks, and procedural time.

TGF-beta 1 increased splicing out of exons 4 and 5 encoding a heparin binding domain. The minimal induction time for changes in splicing by TGF-beta 1 at the M1 location was 1 h, although this did change total SZP mRNA levels. Inhibition of Smad3 phosphorylation inhibited TGF-beta 1 induced splicing, and SZP protein expression. Recombinant proteins corresponding to isoforms upregulated by TGF-beta 1 had reduced binding. The SZP dimerization domain is located within exon 3.

Conclusions: In conclusion, alternative splicing of SZP is regulated by TGF-beta 1 signaling and may regulate SZP

interaction with hepariniheparan sulfate or other components in the extracellular matrix of articular cartilage by splicing out of the heparin binding domain. (C) 2010 Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International.”
“Objective: Ferroptosis inhibitor To determine the efficacy of clinical Stem Cell Compound Library computed tomographic (CT) imaging to verify postoperative electrode array placement in cochlear implant (CI) patients.

Study Design: Nine fresh cadaver heads underwent clinical CT scanning, followed by bilateral CI insertion and postoperative clinical CT scanning.

Temporal bones were removed, trimmed, and scanned using micro-CT. Specimens were then dehydrated, embedded in either methyl methacrylate or LR White resin, and sectioned with a diamond wafering saw. Histology sections were examined by 3 blinded observers to determine the position of individual electrodes relative to soft tissue structures within the cochlea. Electrodes were judged to be within the scala tympani, scala vestibuli, or in

an intermediate position between scalae.

Results: The position of the array could be estimated accurately MEK162 from clinical CT scans in all specimens using micro-CT and histology as a criterion standard. Verification using micro-CT yielded 97% agreement, and histologic analysis revealed 95% agreement with clinical CT results.

Conclusion: A composite, 3-dimensional image derived from a patient’s preoperative and postoperative CT images using a clinical scanner accurately estimates the position of the electrode array as determined by micro-CT imaging and histologic analyses. Information obtained using the CT method provides valuable insight into numerous variables of interest to patient performance such as surgical technique, array design, and processor programming and troubleshooting.”
“Annona crassiflora Mart. is a typical fruit of the Brazilian cerrado, considered to be a species of economic interest, mainly for its use in cooking, which is widespread among the inhabitants of that region, and can be found in many typical local dishes, especially sweets, jellies, liqueurs, soft drinks, ice creams and juices. Thus, the objective of this study was to determine the bioactive substance con tents and the antioxidant capacity of the lipid fraction of A.

This economic relationship resulted in the eventual domestication of Rangifer. The hypothesis of whether domestication was achieved as early as the Late Palaeolithic, and whether this required the use of domesticated dogs (Canis familiaris) as hunting, herding or transport aids, is tested via a comparative analysis using material culture-based phylogenies and ecological datasets in relation to demographic/genetic proxies. Only weak evidence for sustained niche construction

behaviours by prehistoric hunter-gatherer in southern Scandinavia is found, but this study nonetheless provides interesting insights into the likely processes of dog and reindeer domestication, and into processes of adaptation in Late Glacial foragers.”
“Background. Selleckchem ABT-263 a 31-year-old woman with an 11-year history of poorly controlled type 1 diabetes mellitus was admitted 3-MA with severe vomiting and ketoacidosis. the patient had been admitted to hospital on 14 occasions in the past 3 years for diabetic ketoacidosis precipitated by intractable vomiting, and she had been diagnosed with gastroparesis 2 years previously.

Investigations. assessment of the patient’s response to standard treatments for diabetic gastroparesis. these approaches involved tight glycemic control that included subcutaneous

insulin infusion via a pump, correction of electrolyte disturbances, use of standard antiemetic and promotility agents, somatostatin-analog treatment, intrapyloric injection

of botulinum toxin, and insertion of a percutaneous jejunal feeding tube.

Diagnosis. severe diabetic gastroparesis refractory to standard treatments.

Management. the neurokinin-receptor antagonist aprepitant was started and her vomiting stopped within 24 h. this treatment was successfully continued for 4 months until a gastric electrical stimulation device was inserted, which enabled aprepitant treatment to be withdrawn and the percutaneous jejunostomy feeding tube to be removed. this successful treatment led to a substantial improvement in the patient’s quality of life and overall glycemic control.”
“Stress migration (SM) reliability data have been treated qualitatively to define pass or fail criteria in the past. However, realistic quantitative SM analysis and lifetime estimates for CAL-101 PI3K/Akt/mTOR inhibitor products were not available due to lack of a suitable SM model. In this paper, we establish a comprehensive SM model for quantitative stress-induced-voiding (SIV) risk analysis for 32 nm technology and beyond. It was found that the SIV risk is dependent on both stress temperatures and geometric structural line widths as driving forces. Based on the new SM model, the SM lifetime can be estimated from measurable SM data and accelerated SM test methods can be designed to meet the qualification criteria. (C) 2011 American Institute of Physics. [doi:10.1063/1.

The phytotoxicity of 1,3,5-TCB is species-dependent, with Typha demonstrating

significantly higher tolerance than Phragmites. The concentration of 1,3,5-TCB causing zero growth of Phragmites was determined to be 1575 mg TCB/kg dry sediment. The concentration has to be doubled to completely inhibit the growth of BAY 73-4506 inhibitor Typha. Adverse effects of chlorinated benzenes in sediments on Typha increased with decreasing chlorine atoms. The concentrations causing zero growth of Typha are 5765 mg HCB/kg dry soil, 3157 mg 1,3,5-TCB/kg dry soil, and 1325 mg 1,4-DCB/kg dry soil. The higher toxicity of 1,4-DCB than 1,3,5-TCB and HCB in sediment was ascribed to its higher availability and easiness to be taken up by plants, The conclusion was supported by both growth rate calculations and plant height measurements. (C) 2009 Wiley Periodicals, Inc. Environ Toxicol 24: 43-48, 2009.”
“Objective.

To compare the effect of early epidural analgesia (EEA) vs. conventional epidural analgesia (CEA) on cytokine production in mother and neonate.

Methods. Healthy parturients with uncomplicated term pregnancies were randomized into two groups: EEA – parturients who would receive epidural analgesia before onset of pain and the control group, CEA – parturients who would receive epidural analgesia after onset of pain. Cytokines were measured in maternal blood at randomization Visual Analog Scale (VAS) < 30], 24 h postpartum, and in cord blood.

Results. Forty-one women were studied. Epidural was performed in EEA when VAS was 23 +/- 10 and in CEA FK228 cell line when VAS was77 +/- 10 (p < 0.0001). Background LDC000067 ic50 data were similar except for ruptured membranes at admission (EEA 15%, CEA 46.6%; p = 0.03), transient hypotension (EEA 20%, CEA 0%; p = 0.03), and meconium (EEA 25%, CEA 0%; p = 0.01). No significant differences were found in cytokine levels between groups at any time. Interleukin (IL)-6 levels changed significantly only in the control group (p = 0.046). There was significant correlation between baseline maternal IL-6 level

and cord blood level in CEA (r = 0.59, p = 0.005), while no significant correlation existed in EEA (r = 0.33, p = 0.16).

Conclusion. Although there was no significant difference in cytokine levels between the groups, EEA prevented the significant increase in IL-6 during labor and interrupted IL-6 fetal-maternal dependency.”
“The purpose of this review is to evaluate the influence of bariatric surgery on the use and pharmacokinetics of some frequently used drugs. A PubMed literature search was conducted. Literature was included on influence of bariatric surgery on pharmacoepidemiology and pharmacokinetics. Drug classes to be searched for were antidepressants, antidiabetics, statins, antihypertensive agents, corticosteroids, oral contraceptives, and thyroid drugs. A reduction in the use of medication by patients after bariatric surgery has been reported for various drug classes.

“
“We measure the lasing dynamics of single and coupled photonic crystal nanocavity array lasers fabricated in the indium gallium arsenide phosphide material system. Under short optical excitation, single cavity lasers produce pulses

as fast as 11 ps (full width at half maximum), while coupled cavity lasers show significantly longer lasing duration which is not explained by a simple rate equation model. A finite difference time domain simulation including carrier gain and diffusion suggests that asynchronous lasing across the nanocavity array extends the laser’s pulse duration. (C) 2009 American https://www.selleckchem.com/products/LY2603618-IC-83.html Institute of Physics. [DOI: 10.1063/1.3116563]“
“Objective: Anxiety disorders have been shown to undermine the quality of life of cancer patients. Unfortunately, medical professionals often neglect to screen for anxiety in their patients. The aim of the present study was to describe the prevalence of anxiety in patients awaiting diagnostic procedures in an oncology center waiting room, and to investigate possible relationships between anxiety and demographic and clinical variables.

Methods: A cross-sectional study was performed with 398 patients who completed a self-administered questionnaire this website containing

the Hospital Anxiety and Depression Scale (HADS) and the State-Trait Anxiety Inventory (STAI).

Results: Results of the HADS indicated that 38% of participants had anxiety, while data from the STAI showed that 46% had either high state or trait anxiety. The most frequently cited source of anxiety was concern over test results. selleck chemicals Age, gender, employment status, and education level were correlated with anxiety.

Conclusions: The prevalence of anxiety is high among patients awaiting diagnostic procedures. Patients in the waiting room should be routinely screened for anxiety. Careful assessment and treatment of anxiety are important

components in the care of patients with cancer. Copyright (C) 2010 John Wiley & Sons, Ltd.”
“Purpose: We identify the expression of PRL-3 in primary endometrioid endometrial cancer and metastases in relation to the clinicopathological characteristics.

Material/Methods: The study involved 30 patients with type I endometrial cancer. Twelve of them were diagnosed with metastases in various localization of abdomen. The PRL-3 expression was evaluated on the basis of immunohistochemistry results by the use of monoclonal antibody anti-PRL3 clone 3B6.

Results: The intensity of PRL-3 expression in correlation with tumor stage was statistically significant (p = 0.024). The strongest reaction was noted in cases classified as a 1a and 1b stage defined by FIGO. The strength of PRL-3 expression is significantly associated with the degree of histological tumor grade (p = 0.035).

0 and 5.5 to 10.5, respectively. Out of various kinetic models applied, the pseudo second-order kinetic equation has been found to fit well on the kinetic uptake data. The pseudo second-order rate constants buy 3-MA for adsorption have been found to be 0.982 x 10(-2), 7.24 x 10(-2), and 18.09 x 10(-2) min(-1) mg(-1) g for drug solutions with initial concentrations of 10, 20, and 30 mg respectively. The overall sorption process has been found to be governed by intraparticle diffusion The sorptive removal of drug from aqueous solution has also resulted in enhancement in bacterial growth of Escherichia coli. (C) 2010 Wiley Periodicals, Inc. J Appl Polym Sci 117: 3615-3622, 2010″
“The

most-used treatments for epilepsy worldwide are older-generation drugs such as phenytoin, carbamazepine, phenobarbital, and valproic check details acid, which have prominent enzymatic effects. Our sense of comfort with these treatments is starting to fade, however, as more and more potential long-term consequences of these drugs come to light. Epidemiologic studies demonstrate that ischemic disease of the heart and brain is more common among patients with epilepsy. Enzyme-inducing drugs are associated with elevations in a host of surrogate markers of vascular risk, suggesting that they could be responsible for increased

rates of cardiovascular and cerebrovascular disease. The enzyme-inhibiting drug valproate may have adverse consequences of its own pertaining to glucose and lipid metabolism. These effects stand in addition to those well established in the literature regarding bone metabolism, hormonal abnormalities, and drug-drug interactions. Because patients with epilepsy require medication for years, and often for life, it is difficult to justify the long-term use of these agents when there are capable alternatives. Many of the adverse effects of the older drugs appear to be rapidly reversible, prompting consideration of whether patients who are currently treated

LY3023414 with these agents should be switched to alternative therapies, even in the absence of obvious side effects. Newer medications without effects on hepatic enzymes likely do not have these chronic metabolic consequences, and we recommend their use over older-generation drugs whenever possible.”
“Objective. To compare the accuracy of 3 different electronic apex locators (EALs) in establishing the working length in recently extracted teeth.

Study design. Sixty teeth (100 canals) were soaked in an alginate model and electronically measured with 3 EALs (Dentaport ZX, Raypex 5, and Elements Diagnostic Unit and Apex Locator). The real working length was calculated as 1.0 mm short of the real length of the canal. The electronic measurements were taken following the manufacturers’ orientations within +/-0.05 mm and +/-1.0 mm using a #15 K-file attached to the holder, after canal irrigation with 1% NaOCl. Data were analyzed with Friedman test and Wilcoxon signed rank test, at a significance level of 5%.

Results.

In a series of 53 water bath tests, student Nutlin-3 purchase owned thermometers recorded similar mean values to those of a traceable (reference) digital thermometer, Cornell mercury thermometer readings were 0.2 degrees C higher. 10 individual digital thermometers were repeatedly tested

against a traceable thermometer in a water bath, one was inaccurate. In a separate experiment a trained clinician tested the effect of angle of insertion of a digital thermometer on temperature readings and the affect was <0.1 degrees C. We conclude that accurate temperature measurements using digital thermometers are only likely if the thermometer is inserted to the beginning of the window and the thermometer’s accuracy is checked periodically. (C) 2010 Elsevier Ltd. All rights reserved.”
“In this work, polymer films of low density polyethylene and ethylene-vinyl acetate copolymers containing two types of antifog additives (nonionic surfactants) were exposed to two simulated horticultural greenhouse environments, reproducing hot and cold climate conditions. The evolution of the antifog effect was visually observed and that of the additive concentration measured using Fourier transform infrared spectroscopy

(FTIR). All the films studied showed good antifog properties, but in all cases, the duration of the antifog effect was longer in the hot-climate test. From the FTIR, we can conclude that the additives Studied showed a low migration rate and, therefore, when Milciclib molecular weight the antifog effect is lost, important quantities of the additive remain in the bulk. (C) 2008 Wiley Periodicals, Inc. J Appl Polym Sci 111: 2299-2307, 2009″
“Twenty overweight/obese adolescents underwent six months of Kung Fu or placebo (Tai Chi) training, 3x.wk(-1). Outcomes included fasting insulin and insulin resistance, lipids, glucose and HbA(1c), and C-reactive protein (CRY). CRY decreased

KU-55933 chemical structure significantly (p = 0.03) in both groups over time at six months. Although insulin sensitivity did not change, HbA(1c) tended to decrease over time (p = 0.09), again with no group difference (p = 0.60). Reduced CRP was related to increased upper body strength (p = 0.01). Increased lean body mass was related to reductions in HbA(1c), insulin resistance, triglycerides, and total cholesterol. Improvements in lean body mass appear to have a potential role in favorable metabolic outcomes, independent of changes in fat mass. Further research in this area is warranted before definite conclusions can be drawn about the efficacy of martial arts training for metabolic outcomes in this cohort.”
“The effect of melatonin during in vitro maturation (IVM) on DNA damage of cumulus cells (CCs) from bovine cumulus-oocyte complexes (COCs) and embryo development was evaluated. COCs from abattoir ovaries were cultured in maturation medium (MM) with 0.5 mu g/ml FSH and 5.

Results-15 dogs were treated

by means of apicoectomy and retrograde filling following a failed or complicated orthograde root canal treatment. The mean long-term follow-up time was 15.2 months (range, 3 to 50 months). On radiographic evaluation, 10 of 15 dogs had successful resolution of the periapical disease; 5 Bcl-2 cancer dogs had no radiographic evidence of failure of endodontic treatment. All dogs were considered to have a successful clinical outcome.

Conclusions and Clinical Relevance-Surgical endodontic treatment was an effective option for salvaging endodontically diseased but periodontally healthy teeth of dogs in which orthograde treatment was unsuccessful and nonsurgical retreatment was unlikely to succeed. (J Am Vet Med Assoc 2012;241:1633-1638)”
“The content of proanthocyanidins (PA) in foods is usually determined by HPLC analysis of aqueous-organic extracts. However, the appreciable amounts of PA that remain in the residues of extraction usually are not considered for analysis. Attempts to determine these non-extractable proanthocyanidins (NEPA) by enzymatic-chemical methods have obtained partial results. The general aim of this work was the estimation of the total content of PA, including both extractable PA (EPA) and NEPA in some foods included in the USDA database. A specific procedure based on depolymerization

by HCl/BuOH treatment was used to quantify NEPA. The content TEW-7197 of NEPA in analyzed samples ranged from 11 mg/100 g for pear to 6.7 QNZ price g/100g dry weight for red grape pomace. The results showed that literature data underestimate the actual content of PA in foods. NEPA may have a significant contribution to the healthy effects associated to PA-rich foods and diets. (C) 2009 Elsevier Ltd. All rights reserved.”
“Background and Aim:

In patients with type 2 diabetes mellitus, the relationship between lowering glycated hemoglobin (HbA(1c)) and macrovascular complications is not clear and therefore lowering the level. of HbA(1c) is controversial.

Methods and Results: We searched for all, randomized controlled trials comparing the effects of intensive and standard glycemic control on vascular events in patients with type 2 diabetes mellitus. The primary endpoint was combined macrovascular complications, including cardiac events, stroke and peripheral vascular disease. Fixed and random effect models were used to analyze the results.

Eight studies were included according to selection criteria. The results showed no benefits of intensive glycemic control on macrovascular and microvascular complications (P > 0.1), but a higher rate of severe hypoglycemia (P < 0.00001) in the intensive control group when the target HbA(1c) level was <7.0%. When the target HbA(1c) level was lowered to 7.0-7.9%, intensive glycemic control showed benefits on the reduction of microvascular events (P < 0.05) without increasing the risk of severe hypoglycemia (P = 0.