bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nine-Year Effects of 3.7 Years of Intensive Glycemic Control on Cardiovascular Outcomes
Authors:   The ACCORD Study Group
Published: January 2016

OBJECTIVE
In the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, ∼4 years of intensive versus standard glycemic control in participants with type 2 diabetes and other cardiovascular risk factors had a neutral effect on the composite cardiovascular outcome, increased cardiovascular and total mortality, and reduced nonfatal myocardial infarction. Effects of the intervention during prolonged follow-up were analyzed.

RESEARCH DESIGN AND METHODS
All surviving ACCORD participants were invited to participate in the ACCORD Follow-on (ACCORDION) study, during which participants were treated according to their health care provider’s judgment. Cardiovascular and other health-related outcomes were prospectively collected and analyzed using an intention-to-treat approach according to the group to which participants were originally allocated.

RESULTS
A total of 8,601 people, representing 98% of those who did not suffer a primary outcome or death during the ACCORD trial, were monitored for a median of 8.8 years and a mean of 7.7 years from randomization. Intensive glucose lowering for a mean of 3.7 years had a neutral long-term effect on the primary composite outcome (nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death), death from any cause, and an expanded composite outcome that included all-cause death. Moreover, the risk of cardiovascular mortality noted during the active phase (hazard ratio 1.49; 95% CI 1.19, 1.87; P &lt; 0.0001) decreased (HR 1.20; 95% CI 1.03, 1.39; P = 0.02).

CONCLUSIONS
In high-risk people with type 2 diabetes monitored for 9 years, a mean of 3.7 years of intensive glycemic control had a neutral effect on death and nonfatal cardiovascular events but increased cardiovascular-related death.
Modulation of Epileptic Activity in Rats: Focus on Sleep, Physical Exercise and Nitric Oxide–mediated Neurotransmission in a Model of Homocysteine Thiolactone–induced Seizures
Authors: Hrncic Dragan , Rasic-Markovic Aleksandra , Susic Veselinka , Djuric Dragan , Stanojlovic Olivera 
Published: January 2016

ABSTRACT
Epilepsy is a chronic neurological disorder characterised by recurrent epileptic seizures. Understanding the mechanisms by which it initiates and develops, as well as its modulating factors, are of great scientific interest. Experimental models of epilepsy are useful for understanding these mechanisms.
Homocysteine, an amino acid endogenously generated in the body, together with its reactive metabolite, homocysteine thiolactone (HCT), is recognised as a risk factor for a variety of diseases. HCT-induced seizures are a model of generalised epilepsy in which the coexistence of two types of epileptic activity has been documented. Th e complex interplay between sleep and epilepsy is still only poorly understood. Additionally, the relationship between physical exercise and epilepsy is quite intriguing, especially the mechanism underlying this relationship. Th e role of nitric oxide (NO)-mediated neurotransmission in the development of epileptic activity is highly debated in the existing scientific literature .
In this review article, we described the modulation of epileptic activity in rats and focused on sleep, physical activity and NO-mediated signalling. First, we explain the characteristics of the experimental models of epileptic activity and the unique features of HCT-induced seizures. Second, the modulating eff ects of sleep and regular physical exercise training on epileptic activity, along with works from the authors, are discussed. Finally, the anticonvulsive eff ects of NO that is produced via nNOS and iNOS in HCT-induced seizures are reviewed.
Systemic Manifestations of Pseudoexfoliation
Authors: Sarenac-Vulovic Tatjana S. , Janicijevic Petrovic Mirjana A. , Vulovic Dejan D. , Pavlovic Sladjana M. , Simovic Sladjana , Zdravkovic Nemanja S. 
Published: January 2016

ABSTRACT
Objective: Th e aim of our study was to establish a correlation between pseudoexfoliation and its systemic manifestation.
Findings: Pseudoexfoliation syndrome is an agerelated systemic disorder that leads to the overproduction and accumulation of the pseudoexfoliated materials in the visceral organs and in the eye. Many vascular diseases are closely related with pseudoexfoliation manifestations. Our results indicated that there were no statistically significant diff erences (p>0.05) among patients regarding the presence of hypertension in all groups: PEX glaucoma - 45% (9 patients); PEX syndrome- 40% (8 patients); and control groups- 35% (7 patients). Ischemic heart disease was statistically significant present in the sPEX syndrome- 20% (5 patients) and PEX glaucoma- 25% (5 patients) patient groupss, in comparison with those of the control group-10%, (p<0.05). Aortic aneurism was statistically significant present in patients with PEX (syndrome-5% or glaucoma-15%), compared to those in the control group, which included no patients with aneurisms, (p<0.05). Our results indicated that a statistically significant number of patients with aneurism were in the group of patients who developed PEX glaucoma (p<0.05). Cerebrovascular diseases were detected in all groups of patients, but a significant decrease in this metric was noted in the control group- 5% (2 patients), compared with patients with PEX syndrome- 15% and PEX glaucoma-25%, (p<0.05). Hearing loss, as a concomitant sign of PEX manifestation, was recorded in all patients, but in the group with PEX (syndrome-55% or glaucoma-75%), these results showed a statistically significant increase (p<0.05) in comparison with those of patients in the control group (10%). Among the patients with PEX (syndrome and glaucoma), there were no statistically significant diff erences in the selected categories of systemic manifestations (p<0.05). Th is result indicates that the main risk for systemic manifestation is the presence of PEX and that other ocular and vascular complications are, in fact, consequences of PEX.
Conclusion: Pseudoexfoliation is strongly related to systemic vascular disturbances. A detailed examination of patients with PEX by specialists in internal disease or by neurologists should be performed. Such recommended examinations can be helpful in the prevention of diff erent vascular diseasess among patients with PEX, especially atthose in the early stages.
Susceptibility of Diabetic Heart to Catecholamine-induced Arrhythmias is Independent of Contractile Dysfunction
Authors: Adameova Adriana , Elimban Vijayan , Rodriguez-Leyva Delfin , Tappia Paramjit S. , Dhalla Naranjan S 
Published: January 2016

ABSTRACT
Background: Diabetes is associated with myocardial electrical instability and prolongation of action potential duration that result in disturbances in the rhythm of the heart.

Objective: Th is study was undertaken to examine the role of circulating catecholamines in abnormal cardiac rhythm and contractility during diff erent stages of diabetes.

Methods: Diabetes was induced in male Sprague-Dawley rats with streptozotocin (STZ; 65 mg/kg, i.v.). Epinephrine (4-128 μg/kg, i.v.) -induced arrhythmias and plasma levels of epinephrine (Epi) and norepinephrine (NE) were determined in control, 4- and 8-wk diabetic animals. Echocardiography was used to assess cardiac remodeling and contractile function.

Results: Although diabetes induced cardiac dysfunction, there were no significant differences in cardiac output, ejection fraction, left ventricle (LV) dimensions, LV fractional shortening between the 4- and 8-wk diabetic animals. Th e electrocardiogram of both diabetic groups showed deep S wave as well as changes in T wave and ST segment. In addition, prolongation of the RR interval in the 4- and 8-wk diabetic animals was seen, while prolongation of the QT and PR intervals were only seen in the 8-wk diabetic animals. Th e severity of Epi-induced ventricular arrhythmias, as assessed by arrhythmia score, was significantly lower in the 8-wk diabetic rats, as compared to the 4-wk diabetic animals. Circulating Epi levels were significantly decreased in the 8-wk diabetic rats, whereas NE levels were increased in the 4-wk diabetic rats.

Conclusions: Th e sensitivity of the diabetic heart to catecholamine- triggered arrhythmias may be dependent on circulating Epi rather than NE and thus it can be proposed that the increased incidence of sudden cardiac death in diabetics may not be associated with response to catecholamines.
The Influence of Antipsychotics on the Quality of Life of Patients with Schizophrenia in a Long-stay Psychiatric Facility
Authors: Kitic Aleksandra Petrovic , Jankovic Slobodan 
Published: January 2016

ABSTRACT
Introduction: Many factors concomitantly influence the quality of life of patients with schizophrenia in a long-stay psychiatric facility. Th e appropriate selection of antipsychotics and the intensity of their adverse effects exert a significant influence on the quality of life of these patients. Th e aim of this study was to identify the influence of antipsychotic-related factors on the quality of life of patients with schizophrenia.

Methods: Th e study included 102 beneficiaries at the Institute for Accommodation of Adults “Male Pčelice” in Kragujevac. Th e patients were interviewed on in one day using the questionnaire issued by the World Health Organization. The specified data were obtained from the health files of the beneficiaries. We performed a comparison between patients receiving only atypical antipsychotics, typical antipsychotics or a combination thereof.

Results: Th e patients who were receiving only atypical antipsychotics demonstrated better physical health quality of life scores in comparison to those who received combined antipsychotics (77.14 vs. 68.57; U = 332.0; p = 0.02). A statistically significant difference in the mental health quality of life domain was observed between groups of patients receiving various antipsychotic treatments (31.96 vs. 55.27 vs. 49.46; c2 = 7.02; p = 0.03).

Conclusion: Patients in a long-stay psychiatric facility who received atypical antipsychotics demonstrated a better quality of life in comparison to those who received typical antipsychotics, possibly due to the superior safety profile of atypical antipsychotics and a greater feeling of individual contentment.
Unfolded Protein Response Is Activated in the Hearts of Catecholaminergic Polymorphic Ventricular Tachycardia (Cpvt) Mice
Authors: Bakiu Rigers 
Published: January 2016

Abstract
Isoform 2 of calsequestrin (CSQ2) is the main calciumbinding protein of the sarcoplasmic reticulum (SR) and is expressed in both cardiac and skeletal muscle. CSQ2 acts as an SR calcium (Ca2+) sensor and regulates SR Ca2+ release via interactions with triadin, junctin, and the ryanodine receptor. Various mutations of the csq2 gene lead to altered Ca2+ release and contractile dysfunction and contribute to the development of arrhythmias and sudden cardiac death in young individuals affected by CPVT . Transgenic mice carrying one of the identified CSQ2 point mutations (R33Q) associated with CPVT were developed, and a drastic reduction in the mutated protein was observed. Following a biomolecular approach, several analyses were performed using different antibody treatments to identify when the reduction of CSQ2 begins, to unveil the mechanism involved in the reduction of CSQ2 and to verify whether other proteins are affected by the presence of the mutated protein. Th e results of this study showed that mutated CSQ2 levels decreased soon after birth, in conjunction with decreased levels of other important junctional SR proteins, including triadin (TD). Th e up-regulation of proteins associated with the unfolded protein response (UPR) was also observed, and the ATF6- dependent pathway was activated by the UPR. The presence of the R33Q mutation induced the decrease of CSQ2 via UPR activation and subsequent proteasomal degradation.
Behavioural Effects of Short-term Total Food Restriction in Rats
Authors: Selakovic Dragica , Joksimovic Jovana 
Published: January 2016

Abstract
Reducing food intake can decrease anxiety indices in rats. Th e aim of this study was to evaluate the influence of short-term (48 hours) total food restriction on the behavioural characteristics, the motor coordination and balance, of rats. Th ree-month-old male Wistar albino rats (n=20) weighing 350-400 g were divided into a control group (food and water intake ad libitum) and an experimental group (total food restriction 48 hours before testing). Behavioural studies were performed using the open field, elevated plus maze, Barnes maze, beam walking, evoked beam walking and linear locomotor tests. Th e total distance moved, the velocity, the movement and the frequency in the centre zone of the open field were significantly higher in the treated group. Th e cumulative duration in the centre zone of the open field did not significantly increase in the treated group. Th e number of entries into the open arms, the total time spent in the open arms and the total distance moved in the elevated plus maze significantly increased with no change in the velocity in the food-restricted animals. Th e 48 hours of total food restriction did not affect the Barnes maze test parameters or the parameters of the linear locomotor test. Th e velocity recorded during the beam walking test was not affected by the food restriction, but the velocity recorded during the evoked beam walking test significantly decreased in the treated group. In summary, short-term total food restriction did not produce significant changes in the physical performance of rats but did result in anxiolytic- like behaviour accompanied by food-seeking behaviour due to enhanced motivation to forage for food.
The Role of Autophagy in Immunity and Autoimmune Diseases / Uloga Autofagije U Imunskom Odgovoru I Autoimunskim Bolestima
Authors: Markovic Bojana Simovic , Vucicevic Ljubica , Bojic Sanja , Volarevic Vladislav 
Published: January 2016

ABSTRACT
Autophagy is a catabolic mechanism in the cell that involves the degradation of unnecessary or dysfunctional cellular components by the lysosomal machinery. Recent studies have indicated that autophagy is a source of autoantigens, thus highlighting its potential role in the pathogenesis of autoimmunity. There are at least three different forms of autophagy: macroautophagy, microautophagy and chaperone-mediated autophagy (CMA). The physiological role of autophagy is to maintain cellular homeostasis by removing long-lived, damaged proteins and dysfunctional organelles and by providing energy. Aberrant autophagy may contribute to chronic inflammatory diseases and autoimmune diseases.
An understanding of the complex relationships between autophagy and autophagy-related genes in each autoimmune disease creates the possibility of developing more specific and effective therapeutic strategies. Given the importance of autophagy in immune functions, this review article summarises current knowledge about the role of autophagy in the pathogenesis of autoimmune diseases.
Real-time intraoperative monitoring of brainstem auditory evoked potentials during microvascular decompression for hemifacial spasm
Authors: Joo Byung-Euk , Park Sang-Ku , Cho Kyung-Rae , Kong Doo-Sik , Seo Dae-Won , Park Kwan 
Published: January 2016

OBJECTIVE
The aim of this study was to define a new protocol for intraoperative monitoring (IOM) of brainstem auditory evoked potentials (BAEPs) during microvascular decompression (MVD) surgery to treat hemifacial spasm (HFS) and to evaluate the usefulness of this new protocol to prevent hearing impairment.

METHODS
To define the optimal stimulation rate, estimate the number of trials to be averaged, and identify useful warning criteria in IOM of BAEPs, the authors performed a preliminary study of 13 patients with HFS in 2010. They increased the stimulation rate from 10.1 Hz/sec to 100.1 Hz/sec by 10-Hz increments, and they elevated the average time from 100 times to 1000 times by 100-unit increments at a fixed stimulus rate of 43.9 Hz. After defining the optimal stimulation rate and the number of trials that needed to be averaged for IOM of BAEPs, they also identified the useful warning criteria for this protocol for MVD surgery. From January to December 2013, 254 patients with HFS underwent MVD surgery following the new IOM of BAEPs protocol. Pure-tone audiometry and speech discrimination scoring were performed before surgery and 1 week after surgery. To evaluate the usefulness of the new protocol, the authors compared the incidence of postoperative hearing impairment with the results from the group that underwent MVD surgery prior to the new protocol.

RESULTS
Through a preliminary study, the authors confirmed that it was possible to obtain a reliable wave when using a stimulation rate of 43.9 Hz/sec and averaging 400 trials. Only a Wave V amplitude loss > 50% was useful as a warning criterion when using the new protocol. A reliable BAEP could be obtained in approximately 9.1 seconds. When the new protocol was used, 2 patients (0.8%) showed no recovery of Wave V amplitude loss > 50%, and only 1 of those 2 patients (0.39%) ultimately had postoperative hearing impairment. When compared with the outcomes in the pre-protocol group, hearing impairment incidence decreased significantly among patients who underwent surgery with the new protocol (0.39% vs 4.02%, p = 0.002). There were no significant differences between the 2 surgery groups regarding other complications, including facial palsy, sixth cranial nerve palsy, and vocal cord palsy.

CONCLUSIONS
There was a significant decrease in postoperative hearing impairment after MVD for HFS when the new protocol for IOM of BAEPs was used. Real-time IOM of BAEPs, which can obtain a reliable BAEP in less than 10 seconds, is a successful new procedure for preventing hearing impairment during MVD surgery for HFS.
Differences between C3–4 and other subaxial levels of cervical disc arthroplasty: more heterotopic ossification at the 5-year follow-up
Authors: Chang Peng-Yuan , Chang Hsuan-Kan , Wu Jau-Ching , Huang Wen-Cheng , Fay Li-Yu , Tu Tsung-Hsi , Wu Ching-Lan , Cheng Henrich 
Published: January 2016

OBJECTIVE
Several large-scale clinical trials demonstrate the efficacy of 1- and 2-level cervical disc arthroplasty (CDA) for degenerative disc disease (DDD) in the subaxial cervical spine, while other studies reveal that during physiological neck flexion, the C4–5 and C5–6 discs account for more motion than the C3–4 level, causing more DDD. This study aimed to compare the results of CDA at different levels.

METHODS
After a review of the medical records, 94 consecutive patients who underwent single-level CDA were divided into the C3–4 and non-C3–4 CDA groups (i.e., those including C4–5, C5–6, and C6–7). Clinical outcomes were measured using the visual analog scale for neck and arm pain and by the Japanese Orthopaedic Association scores. Postoperative range of motion (ROM) and heterotopic ossification (HO) were determined by radiography and CT, respectively.

RESULTS
Eighty-eight patients (93.6%; mean age 45.62 ± 10.91 years), including 41 (46.6%) female patients, underwent a mean follow-up of 4.90 ± 1.13 years. There were 11 patients in the C3–4 CDA group and 77 in the non-C3–4 CDA group. Both groups had significantly improved clinical outcomes at each time point after the surgery. The mean preoperative (7.75° vs 7.03°; p = 0.58) and postoperative (8.18° vs 8.45°; p = 0.59) ROMs were similar in both groups. The C3–4 CDA group had significantly greater prevalence (90.9% vs 58.44%; p = 0.02) and higher severity grades (2.27 ± 0.3 vs 0.97 ± 0.99; p = 0.0001) of HO.

CONCLUSIONS
Although CDA at C3–4 was infrequent, the improved clinical outcomes of CDA were similar at C3–4 to that in the other subaxial levels of the cervical spine at the approximately 5-year follow-ups. In this Asian population, who had a propensity to have ossification of the posterior longitudinal ligament, there was more HO formation in patients who received CDA at the C3–4 level than in other subaxial levels of the cervical spine. While the type of artificial discs could have confounded the issue, future studies with more patients are required to corroborate the phenomenon.
Emergency room resource utilization by patients with low-back pain
Authors: Drazin Doniel , Nuño Miriam , Patil Chirag G. , Yan Kimberly , Liu John C. , Acosta Frank L. 
Published: January 2016

OBJECTIVE
The objective of this study was to determine factors associated with admission to the hospital through the emergency room (ER) for patients with a primary diagnosis of low-back pain (LBP). The authors further evaluated the impact of ER admission and patient characteristics on mortality, discharge disposition, and hospital length of stay.

METHODS
The authors conducted a retrospective analysis of patients with LBP discharged from hospitals according to the Nationwide Inpatient Sample (NIS) between 1998 and 2007. Univariate comparisons of patient characteristics according to the type of admission (ER versus non-ER) were conducted. Multivariate analysis evaluated factors associated with an ER admission, risk of mortality, and nonroutine discharge.

RESULTS
According to the NIS, approximately 183,151 patients with a primary diagnosis of LBP were discharged from US hospitals between 1998 and 2007. During this period, an average of 65% of these patients were admitted through the ER, with a significant increase from 1998 (54%) to 2005 (71%). Multivariate analysis revealed that uninsured patients (OR 2.1, 95% CI 1.7–2.6, p < 0.0001) and African American patients (OR 1.5, 95% CI 1.2–1.7, p < 0.0001) were significantly more likely to be admitted through the ER than private insurance patients or Caucasian patients, respectively. Additionally, a moderate but statistically significant increase in the likelihood of ER admission was noted for patients with more preexisting comorbidities (OR 1.1, 95% CI 1.0–1.2, p < 0.001). An 11% incremental increase in the odds of admission through the ER was observed with each year increment (OR 1.1, 95% CI 1.0–1.2, p < 0.001). Highest income patients ($45,000+) were more likely to be admitted through the ER (OR 1.3, 95% CI 1.1–1.6, p = 0.007) than the lowest income cohort. While ER admission did not impact the risk of mortality (OR 0.95, 95% CI 0.60–1.51, p = 0.84), it increased the odds of a nonroutine discharge (OR 1.39, 95% CI 1.26–1.53, p < 0.0001).

CONCLUSIONS
A significant majority of patients discharged from hospitals in the US from 1998 to 2007 with a primary diagnosis of LBP were admitted through the ER, with more patients being admitted via this route each year. These patients were less likely to be discharged directly home compared with patients with LBP who were not admitted through the ER. Uninsured and African American patients with LBP were more likely to be admitted through the ER than their counterparts, as were patients with more preexisting health problems. Interestingly, patients with LBP at the highest income levels were more likely to be admitted through hospital ERs. The findings suggest that socioeconomic factors may play a role in the utilization of ER resources by patients with LBP, which in turn appears to impact at least the short-term outcome of these patients.