Akdeniz University Hospital

BACKGROUND: Hyperlipidemia has been suggested as a risk factor for stenosis of the aortic valve, but lipid-lowering studies have had conflicting results. METHODS: We conducted a randomized, double-blind trial involving 1873 patients with mild-to-moderate, asymptomatic aortic stenosis. The patients received either 40 mg of simvastatin plus 10 mg of ezetimibe or placebo daily. The primary outcome was a composite of major cardiovascular events, including death from cardiovascular causes, aortic-valve replacement, nonfatal myocardial infarction, hospitalization for unstable angina pectoris, heart failure, coronary-artery bypass grafting, percutaneous coronary intervention, and nonhemorrhagic stroke. Secondary outcomes were events related to aortic-valve stenosis and ischemic cardiovascular events. RESULTS: During a median follow-up of 52.2 months, the primary outcome occurred in 333 patients (35.3%) in the simvastatin-ezetimibe group and in 355 patients (38.2%) in the placebo group (hazard ratio in the simvastatin-ezetimibe group, 0.96; 95% confidence interval [CI], 0.83 to 1.12; P=0.59). Aortic-valve replacement was performed in 267 patients (28.3%) in the simvastatin-ezetimibe group and in 278 patients (29.9%) in the placebo group (hazard ratio, 1.00; 95% CI, 0.84 to 1.18; P=0.97). Fewer patients had ischemic cardiovascular events in the simvastatin-ezetimibe group (148 patients) than in the placebo group (187 patients) (hazard ratio, 0.78; 95% CI, 0.63 to 0.97; P=0.02), mainly because of the smaller number of patients who underwent coronary-artery bypass grafting. Cancer occurred more frequently in the simvastatin-ezetimibe group (105 vs. 70, P=0.01). CONCLUSIONS: Simvastatin and ezetimibe did not reduce the composite outcome of combined aortic-valve events and ischemic events in patients with aortic stenosis. Such therapy reduced the incidence of ischemic cardiovascular events but not events related to aortic-valve stenosis. (ClinicalTrials.gov number, NCT00092677.)

RATIONALE: Accurate, early identification of patients at risk for developing acute lung injury (ALI) provides the opportunity to test and implement secondary prevention strategies. OBJECTIVES: To determine the frequency and outcome of ALI development in patients at risk and validate a lung injury prediction score (LIPS). METHODS: In this prospective multicenter observational cohort study, predisposing conditions and risk modifiers predictive of ALI development were identified from routine clinical data available during initial evaluation. The discrimination of the model was assessed with area under receiver operating curve (AUC). The risk of death from ALI was determined after adjustment for severity of illness and predisposing conditions. MEASUREMENTS AND MAIN RESULTS: Twenty-two hospitals enrolled 5,584 patients at risk. ALI developed a median of 2 (interquartile range 1-4) days after initial evaluation in 377 (6.8%; 148 ALI-only, 229 adult respiratory distress syndrome) patients. The frequency of ALI varied according to predisposing conditions (from 3% in pancreatitis to 26% after smoke inhalation). LIPS discriminated patients who developed ALI from those who did not with an AUC of 0.80 (95% confidence interval, 0.78-0.82). When adjusted for severity of illness and predisposing conditions, development of ALI increased the risk of in-hospital death (odds ratio, 4.1; 95% confidence interval, 2.9-5.7). CONCLUSIONS: ALI occurrence varies according to predisposing conditions and carries an independently poor prognosis. Using routinely available clinical data, LIPS identifies patients at high risk for ALI early in the course of their illness. This model will alert clinicians about the risk of ALI and facilitate testing and implementation of ALI prevention strategies. Clinical trial registered with www.clinicaltrials.gov (NCT00889772).

Forty five insulin dependent diabetics were randomised to treatment with continuous subcutaneous insulin infusion (CSII), multiple insulin injections (five or six daily), or conventional twice daily insulin injections. Near normoglycaemia was obtained with CSII and multiple injections but not with conventional treatment (p less than 0.01). Hypoglycaemic coma was observed less frequently with CSII than with multiple injections and conventional treatment (p less than 0.001), but blood glucose concentrations below 2.5 mmol/l (45 mg/100 ml) were more common. After two years fewer retinal microaneurysms and haemorrhages had developed in the patients given CSII and multiple injections compared with those given conventional treatment, in whom the number had increased significantly (p less than 0.01). Motor nerve conduction velocity deteriorated in the patients given conventional treatment; in those given CSII it was unchanged during the first year but had improved after two years (p less than 0.01). Glomerular hyperfiltration was reduced with CSII, but no change occurred in urine albumin excretion rates. Long term near normoglycaemia may prevent the progression of early stages of late diabetic complications.

BACKGROUND: Urinary and sexual dysfunction are recognized complications of rectal excision for cancer. The aim of this study was to examine the frequency of such complications after mesorectal excision, shortly after this method was introduced. METHODS: Spontaneous flowmetry, residual volume of urine measurement and urodynamic examination, including cystometry and simultaneous detrusor pressure and urinary flow recording, was carried out before and 3 months after curative rectal excision. Urinary symptoms and sexual function were evaluated by means of questionnaires before and after operation. Each patient served as his or her own control. RESULTS: Forty-nine consecutive patients, 39 of whom had a total mesorectal excision (TME) and ten a partial mesorectal excision, were examined before surgery and 35 again after operation. In two patients, a weak detrusor was detected before operation. Two patients developed signs of bladder denervation after operation. Transitory moderate urinary incontinence appeared in four other women. Six of 24 men reported some reduction in erectile function and one became impotent. Two men reported retrograde ejaculation. All the complications were seen in the TME group. CONCLUSION: Mesorectal excision for rectal cancer resulted in a low frequency of serious bladder and sexual dysfunction.

TLRs constitute an essential family of pattern recognition molecules that, through direct recognition of conserved microbial components, initiate inflammatory responses following infection. In this role, TLR1 enables host responses to a variety of bacteria, including pathogenic species of mycobacteria. In this study, we report that I602S, a common single nucleotide polymorphism within TLR1, is associated with aberrant trafficking of the receptor to the cell surface and diminished responses of blood monocytes to bacterial agonists. When expressed in heterologous systems, the TLR1 602S variant, but not the TLR1 602I variant, exhibits the expected deficiencies in trafficking and responsiveness. Among white Europeans, the 602S allele represents the most common single nucleotide polymorphism affecting TLR function identified to date. Surprisingly, the 602S allele is associated with a decreased incidence of leprosy, suggesting that Mycobacterium leprae subverts the TLR system as a mechanism of immune evasion.

Abstract This study examined the longitudinal relationship between work–family interaction (WFI) in terms of the direction of influence (work-to-family vs. family-to-work) and type of effect (conflict vs. facilitation) and burnout. A sample of 2235 respondents from eight different occupational groups (lawyers, bus drivers, employees within information technology, physicians, teachers, church ministers, employees within advertisement, and nurses) supplied data at two points in time with a 2-year time interval. Building upon Hobfoll's (1989) Conservations of Resources (COR) theory, three causal models were proposed. The results of SEM-analyses revealed evidence for both a normal (WFI → burnout), a reverse (WFI ← burnout), and a reciprocal (WFI ↔ burnout) relationship. In general, there were lagged positive effects between the conflict dimensions of WFI and burnout and lagged negative effects between the facilitation dimension of WFI and burnout. One exception was a significant lagged negative effect between disengagement at Time 1 and work-to-family conflict at Time 2, suggesting that distancing oneself from job might act as a coping strategy causing lower levels of work-to-family conflict.

OBJECTIVE: The benefit of continuous on-site presence by a staff academic critical care specialist in the intensive care unit of a teaching hospital is not known. We compared the quality of care and patient/family and provider satisfaction before and after changing the staffing model from on-demand to continuous 24-hr critical care specialist presence in the intensive care unit. DESIGN: Two-year prospective cohort study of patient outcomes, processes of care, and family and provider survey of satisfaction, organization, and culture in the intensive care unit. SETTING: Intensive care unit of a teaching hospital. PATIENTS: Consecutive critically ill patients, their families, and their caregivers. INTERVENTIONS: Introduction of night-shift coverage to provide continuous 24-hr on-site, as opposed to on-demand, critical care specialist presence. MEASUREMENTS AND MAIN RESULTS: Of 2,622 patients included in the study, 1,301 were admitted before and 1,321 after the staffing model change. Baseline characteristics and adjusted intensive care unit and hospital mortality were similar between the two groups. The nonadherence to evidence-based care processes improved from 24% to 16% per patient-day after the staffing change (p = .002). The rate of intensive care unit complications decreased from 11% to 7% per patient-day (p = .023). When adjusted for predicted hospital length of stay, admission source, and do-not-resuscitate status, hospital length of stay significantly decreased during the second period (adjusted mean difference -1.4, 95% confidence interval -0.3 to -2.5 days, p = .017). The new model was considered optimal for patient care by the majority of the providers (78% vs. 38% before the intervention, p < .001). Family satisfaction was excellent during both study periods (mean score 5.87 +/- 1.7 vs. 5.95 +/- 2.0, p = .777). CONCLUSIONS: The introduction of continuous (24-hr) on-site presence by a staff academic critical care specialist was associated with improved processes of care and staff satisfaction and decreased intensive care unit complication rate and hospital length of stay.

In vivo functional imaging by means of positron emission tomography (PET) is the sole method for providing a quantitative measurement of mu-, kappa and delta-opioid receptor-mediated signalling in the central nervous system. During the last two decades, measurements of changes to the regional brain opioidergic neuronal activation--mediated by endogenously produced opioid peptides, or exogenously administered opioid drugs--have been conducted in numerous chronic pain conditions, in epilepsy, as well as by stimulant- and opioidergic drugs. Although several PET-tracers have been used clinically for depiction and quantification of the opioid receptors changes, the underlying mechanisms for regulation of changes to the availability of opioid receptors are still unclear. After a presentation of the general signalling mechanisms of the opioid receptor system relevant for PET, a critical survey of the pharmacological properties of some currently available PET-tracers is presented. Clinical studies performed with different PET ligands are also reviewed and the compound-dependent findings are summarized. An outlook is given concluding with the tailoring of tracer properties, in order to facilitate for a selective addressment of dynamic changes to the availability of a single subclass, in combination with an optimization of the quantification framework are essentials for further progress in the field of in vivo opioid receptor imaging.

This review provides a comprehensive assessment of recent progress in polypyrrole derivatives which are specially designed for electrochromic applications.

In this study, it was aimed to compare different normalization methods employed in model developing process via artificial neural networks with different sample sizes. As part of comparison of normalization methods, input variables were set as: work discipline, environmental awareness, instrumental motivation, science self-efficacy, and weekly science learning time that have been covered in PISA 2015, whereas students' Science Literacy level was defined as the output variable. The amount of explained variance and the statistics about the correct classification ratios were used in the comparison of the normalization methods discussed in the study. The dataset was analyzed in Matlab2017b software and both prediction and classification algorithms were used in the study. According to the findings of the study, adjusted min-max normalization method yielded better results in terms of the amount of explained variance in different sample sizes compared to other normalization methods; no significant difference was found in correct classification rates according to the normalization method of the data, which lacked normal distribution and the possibility of overfitting should be taken into consideration when working with small samples in the modelling process of artificial neural network. In addition, it was also found that sample size had a significant effect on both classification and prediction analyzes performed with artificial neural network methods. As a result of the study, it was concluded that with a sample size over 1000, more consistent results can be obtained in the studies performed with artificial neural networks in the field of education.

The goal of end-of-life care for dying patients is to prevent or relieve suffering as much as possible while respecting the patients' desires. However, physicians face many ethical challenges in end-of-life care. Since the decisions to be made may concern patients' family members and society as well as the patients, it is important to protect the rights, dignity, and vigor of all parties involved in the clinical ethical decision-making process. Understanding the principles underlying biomedical ethics is important for physicians to solve the problems they face in end-of-life care. The main situations that create ethical difficulties for healthcare professionals are the decisions regarding resuscitation, mechanical ventilation, artificial nutrition and hydration, terminal sedation, withholding and withdrawing treatments, euthanasia, and physician-assisted suicide. Five ethical principles guide healthcare professionals in the management of these situations.

This article deals with the investigation of free vibration and buckling behaviors of carbon nanotube (CNT)-reinforced cross-ply laminated composite plates. The plate kinematics is assumed to follow a first-order shear deformation theory (FSDT). After the coupled equations of motion and buckling are derived, the method of discrete singular convolution (DSC) is used for the numerical solution of the problems. Both the regularized Shannon’s and Lagrange’s delta kernels are used for spatial discretizing of the resulting governing equations of buckling and vibration of CNT-reinforced laminated plates. Natural frequencies and critical buckling loads are obtained for different cases. Wherever possible, the present DSC results are verified by comparing them with the existing analytical results available in the literature. Then, a detailed parametric study is performed to examine the effects of boundary conditions, CNT distributions and volume fraction, aspect ratio, length-to-width ratio, and number of layers on the frequencies and buckling loads.

Biomass-derived carbonaceous materials have been deemed to be one of the up-and-coming electrode materials for high-performance energy storage systems due to their cost-neutral abundant resources, sustainable nature, easy synthesis methods, and environmentally benign features. In this work, various graphene-like porous carbon networks (GPCs) with three-dimensional (3D) hierarchically ordered "ion highways" have been synthesized by the carbonization/activation of orange-peel wastes for use as an electrode material in high-energy supercapacitors. The porous structures and surface morphologies of the GPCs were rationally fine-tuned as a function of the activation agent ratio. The prepared GPCs offered superior specific surface area in addition to a 3D porous structure with a fine-tuned pore size distribution. The electrochemical behaviors of all the GPCs were evaluated in 6.0 M KOH aqueous electrolyte via a three-electrode electrochemical setup. Owing to their synergistic characteristics, including superior specific surface area (1150 m2 g-1), large pore volume, and fine-tuned 3D porous architecture, GPC-3.0 (synthesized with a KOH : GPC ratio of 3.0, by wt.) exhibited the best capacitive behavior amongst the studied GPCs. The 3D hierarchically ordered architecture acts like well-designed ion highways that boost electron transportation, thereby enhancing electrochemical energy storage. A coin-cell-type symmetrical supercapacitor based on GPC-3.0 was tested in both 1.0 M Na2SO4 (salt-in-water) and 12.0 m NaNO3 (water-in-salt) electrolytes. The supercapacitor cell based on the water-in-salt electrolyte offered a wide operating voltage of 2.3 V. The obtained energy density and power density values were comparable to those of commercial high-performance electrical double-layer capacitors. Such notable findings will shed light on next-generation high-rate electrochemical energy storage systems based on biomass-derived carbonaceous materials.

BACKGROUND: Alterations in the inflammatory system have been associated with schizophrenia and major depression, while bipolar disorder has been less studied. Most previous studies examined small samples, and the literature is inconsistent with regard to specific underlying immune mechanisms. In the present study, we examined markers representing different inflammatory pathways, and the aim was to investigate whether the levels of inflammatory parameters in a representative sample of bipolar disorder and schizophrenia are elevated compared to healthy controls, and to investigate whether the inflammatory profile is different between the groups. METHODS: Plasma levels of soluble tumor necrosis factor receptor 1 (sTNF-R1), interleukin-1 receptor antagonist (IL-1Ra), interleukin-6 (IL-6), high-sensitivity CRP (hs-CRP), soluble CD40L ligand (sCD40L), and von Willebrand factor (vWf) were measured with ELISA techniques in a catchment area based sample of consecutively referred patients with severe mental disorders [N = 311, comprising bipolar disorder (n = 125) and schizophrenia (n = 186)] and in healthy volunteers (n = 244). RESULTS: Plasma levels of sTNF-R1 and vWf were statistically significantly increased in both bipolar disorder and schizophrenia compared to controls (p < 0.00001), and were also increased in unmedicated patients, but there were no major differences between the two diagnostic groups. Controlling for age, gender, ethnicity, cardiovascular disorders, kidney and liver function, and other confounders did not affect the results. There were no differences in other inflammation factors between the groups. CONCLUSION: The present results indicate specific alterations of endothelium-related inflammation processes in both bipolar disorder and schizophrenia.

The spontaneous behavior of humans can be altered dramatically by repeated exposure to psychomotor stimulants. We have developed a primate model for analyzing the neurobiology underlying such drug-induced behavioral changes. We performed ethogram-based behavioral assays on squirrel monkeys given single or multiple cocaine treatments, and in the same monkeys made anatomical plots of striatal neurons that were activated to express early-gene proteins. A final cocaine challenge after chronic intermittent exposure to cocaine induced highly patterned behavioral changes in the monkeys, affecting individual behavioral motifs in distinct ways. In the striatum, the challenge dose induced striosome-predominant expression combined with intense dorsal early-gene expression, especially in the putamen. These patterns of gene expression were highly predictive of the levels of stereotypy exhibited by the monkeys in response to cocaine challenge. The total levels of expression, on the other hand, appeared to reflect increased spontaneous behavioral activation during the drug-free period after the cocaine exposure. We suggest that in the primate, compartmentally and regionally specific striatal activation patterns contribute to the striatal modulation of psychostimulant-induced behaviors. These observations in nonhuman primates raise the possibility that monitoring such basal ganglia activity patterns could help to delineate the neural mechanisms underlying drug-induced repetitive behaviors and related syndromes in which stereotypies are manifest.

Measurement of red blood cell (RBC) deformability by ektacytometry yields a set of elongation indexes (EI) measured at various shear stresses (SS) presented as SS-EI curves, or tabulated data. These are useful for detailed analysis, but may not be appropriate when a simple comparison of a global parameter between groups is required. Based on the characteristic shape of SS-EI curves, two approaches have been proposed to calculate the maximal RBC elongation index (EI(max)) and the shear stress required for one-half of this maximal deformation (SS(1/2)): (i) linear Lineweaver-Burke (LB) model; (ii) Streekstra-Bronkhorst (SB) model. Both approaches have specific assumptions and thus may be subject to the measurement conditions. Using RBC treated with various concentrations of glutaraldehyde (GA) and data obtained by ektacytometry, the two approaches have been compared for nine different ranges of SS between 0.6-75 Pa. Our results indicate that: (i) the sensitivity of both models can be affected by the SS range and limits employed; (ii) over the entire range of SS-data, a non-linear curve fitting approach to the LB model gave more consistent results than a linear approach; (iii) the LB method is better for detecting SS(1/2) differences between RBC treated with 0.001-0.005% glutaraldehyde (GA) and for a 40% mixture of rigid cells but is equally sensitive to SB for 10% rigid cells; and (iv) the LB and SB methods for EI(max) are equivalent for 0.001% and 0.003% GA and 40% rigid, with the SB better for 0.005% GA and the LB better for 10% rigid.

The accurate and precisive monitoring of aflatoxin B1 (AFB1), which is one of the most hazardous mycotoxins, especially in agricultural products, is significant for human and environmental health.

We propose a method for the automated identification of key white matter fiber tracts for neurosurgical planning, and we apply the method in a retrospective study of 18 consecutive neurosurgical patients with brain tumors. Our method is designed to be relatively robust to challenges in neurosurgical tractography, which include peritumoral edema, displacement, and mass effect caused by mass lesions. The proposed method has two parts. First, we learn a data-driven white matter parcellation or fiber cluster atlas using groupwise registration and spectral clustering of multi-fiber tractography from healthy controls. Key fiber tract clusters are identified in the atlas. Next, patient-specific fiber tracts are automatically identified using tractography-based registration to the atlas and spectral embedding of patient tractography. Results indicate good generalization of the data-driven atlas to patients: 80% of the 800 fiber clusters were identified in all 18 patients, and 94% of the 800 fiber clusters were found in 16 or more of the 18 patients. Automated subject-specific tract identification was evaluated by quantitative comparison to subject-specific motor and language functional MRI, focusing on the arcuate fasciculus (language) and corticospinal tracts (motor), which were identified in all patients. Results indicate good colocalization: 89 of 95, or 94%, of patient-specific language and motor activations were intersected by the corresponding identified tract. All patient-specific activations were within 3mm of the corresponding language or motor tract. Overall, our results indicate the potential of an automated method for identifying fiber tracts of interest for neurosurgical planning, even in patients with mass lesions.

AIM OF THE STUDY: To assess the long-term hepatitis C (HCV) treatment outcome in former injecting drug users (IDUs). MATERIALS AND METHODS: A long-term follow-up of 27 former IDUs who had been successfully treated for chronic hepatitis C was performed. These patients represented all IDUs who had obtained a sustained virological response in a Norwegian HCV treatment trial. The patients had been treated with interferon-alpha alone or in combination with ribavirin. At 5 years' follow-up the 27 IDUs were retested for HCV RNA and risk behaviour for HCV transmission after treatment was assessed. In the control group all 18 non-IDUs who had obtained a sustained virological response in the same treatment trial were included. RESULTS: At follow-up 13-82 months (median 64) after the end of treatment only one case of probable reinfection was seen among the 27 IUDs. No reoccurrence of HCV was observed in the control group. The IDU who was HCV RNA positive at follow-up had continued injecting drugs and reported frequent needle sharing. At follow-up HCV of genotype 1a was detected in contrast to genotype 1b before treatment indicating that this patient was reinfected with HCV. A return to injecting drug use occurred in 9 (33%) of 27 IDUs. CONCLUSION: The long-term outcome of HCV treatment in former IDUs was excellent. Despite frequent reinitiation of drug injection all but 1 remained HCV RNA negative.

Four trials were conducted to compare the concentrations of cottonseed hulls (CSH) and chopped hay in textured starters on calf body weight gain, intake, and efficiency. Holstein bull calves (initially 3 and 4 d old in studies 1, 2, and 3, and 59 to 60 d old in study 4) were fed ad libitum starters (geometric mean particle size of approximately 2,000 22mim; equal at 18% crude protein as-fed; digestible energy concentration declined with increasing roughage). All calves were weaned at 31 to 32 d of age. Calves were housed in individual pens bedded with straw within an unheated, curtain-sided nursery for d 0 to 56 and then grouped in pens of 6 calves for d 56 to 84. Study 1 compared textured starters containing A) 0% or B) 5% CSH for the first 56 d. On d 56 (through d 84), calves fed diet A were switched to diet C, which contained 0% CSH and 5% chopped hay; calves fed diet B were switched to diet D, which contained 5% CSH and 5% hay. Study 2 compared textured starters fed from 0 to 84 d that contained A) 0% CSH and 0% chopped hay, B) 5% CSH, C) 10% CSH, or D) 5% chopped hay. Study 3 compared textured starters fed from 0 to 56 d that contained A) 0%, B) 2.5%, and C) 5% chopped hay. Study 4 compared textured starters fed from d 56 to 84 that contained A) 5% and B) 15% chopped hay. In study 1, calves fed the diet with 5% CSH consumed less starter and were less efficient from 28 to 56 d than calves fed 0% CSH. Calves fed the diet with 0% CSH tended to have a greater average daily gain (ADG) and empty body weight ADG (EBWADG) from 28 to 84 d than calves fed the starter with 5% CSH. In study 2, EBWADG declined linearly from 0 to 28 d, and both ADG and EBWADG decreased from 28 to 56 d as CSH percentage increased in the starter. Both ADG and EBWADG responded quadratically to CSH percentage in the starter from 56 to 84 d, with calves fed the starter containing 10% CSH having the slowest ADG and EBWADG. Calves between 56 and 84 d that were fed starters with 5% roughage appeared more efficient than calves fed starters with 0 or 10% roughage. In study 3, ADG, EBWADG, starter intake, and efficiency declined linearly as hay percentage increased in the starter from 28 to 56 d. In study 4, ADG, EBWADG, and starter intake were less for calves fed starters with 15 vs. 5% hay. In conclusion, adding low-energy fibrous feeds to starters with adequate coarseness (approximately 2,000 microm) reduced ADG in weaned calves less than 3 mo old bedded on straw.