Comparison of long-term outcomes of double kissing crush versus T and minimal protrusion techniques in complex bifurcation lesions: The EVOLUTE-CRUSH II registry.

BACKGROUND: Double kissing (DK)-crush and T-stenting and small protrusion (TAP) techniques are gaining popularity, but the comparison for both techniques is still lacking. This study sought to retrospectively evaluate the long-term outcomes of DK-crush and TAP techniques in patients with complex bifurcation lesions. METHODS: A total of 255 (male: 205 [80.3%], mean age: 59.56 ± 10.13 years) patients who underwent coronary bifurcation intervention at a single-center between January 2014 and May 2021 were included. Angiographic features, procedure details, and in-hospital or long-term outcomes were assessed. The primary endpoint was target lesion failure (TLF), defined as the combination of cardiac death, target vessel myocardial infarction, or clinically driven-target lesion revascularization (TLR). The regression models were adjusted applying by the inverse probability weighted (IPW) approach to reduce treatment selection bias. RESULTS: The initial management strategy was DK-crush in 152 (59.6%) patients and TAP in 103 (40.4%) cases. The SYNTAX scores (24.58 ± 7.4 vs. 24.26 ± 6.39, p = 0.846) were similar in both groups. The number of balloon (6.32 ± 1.82 vs. 3.92 ± 1.19, p < 0.001) usage was significantly higher in the DK-crush group than in the TAP group. The rates of TLF (11.8 vs. 22.3%, p = 0.025) and clinically driven TLR (6.6 vs. 15.5%, p = 0.020) were significantly lower in the DK-crush group compared to the TAP group. The long-term TLF was significantly higher in the TAP group compared to the DK-crush group (unadjusted HR: 1.974, [95% CI: 1.044-3.732], p = 0.035 and adjusted HR [IPW]: 2.498 [95% CI: 1.232-5.061], p = 0.011). CONCLUSION: The present study showed that the DK-crush technique of bifurcation treatment was associated with lower long-term TLF and TLR rates compared to the TAP technique.

Biological Variations of Seven Clinical Chemistry Analytes and Trolox Equivalent Antioxidant Capacity within Salivary Constituents.

BACKGROUND: Data on biological variation in saliva samples are quite limited. This study aimed to obtain well-defined biological variation data for seven common clinical chemistry analytes and Trolox equivalent antioxidant capacity (TEAC) in saliva. METHODS: Unstimulated whole saliva and blood samples were collected from thirty-two healthy volunteers of both genders without any history of disease or metabolic syndrome under standard conditions at six different times within three weeks. The seven clinical chemistry analytes and TEAC, analyzed by photometric methods using automated analyzers, were planned for biological variation analysis. The components of nested analysis of variance were used to perform the biological variation data analysis. RESULTS: The within-subject and between-subject biological variations (CVG and CVI, respectively) for unstimulated whole saliva samples, respectively, were determined to be 19.3% and 25.1% for α-amylase, 25.1% and 51.1% for aspartate aminotransferase, 31.0% and 22.3% for lactate dehydrogenase, 19.0% and 20.8% for uric acid, 16.6% and 23.4% for total calcium, 12.9% and 13.7% for inorganic phosphate, 13.1% and 19.7% for total protein, and 14.9% and 20.0% for TEAC. In addition, the CVI and CVG were 3.4% and 6.3% for serum TEAC. CONCLUSIONS: Considering the evidence that saliva samples can be used to diagnose and monitor oral or non-oral diseases, these biological variation data will contribute to how to use subject-based reference values or population-based reference intervals of these analytes and TEAC.

Biological variation of plasma 25-Hydroxyvitamin D3, Serum vitamin B12, folate and ferritin in Turkish healthy subject.

Biological variation (BV) plays a crucial role in determining analytical performance specifications, assessing serial measurements of individuals, and establishing the use of population-based reference intervals. Our study aimed to calculate the BV and BV-based quality goals of 25-hydroxyvitamin D3 (25-OH D3), ferritin, folate and vitamin B12 tests. We included a total of 22 apparently healthy volunteers (9 women and 13 men) aged 18-55 years in the study that we conducted in Turkey. Blood samples were collected from the participants once a week for five weeks. Serum ferritin, folate and vitamin B12 levels were measured using immunochemical method, while plasma 25-OH D3 levels were determined using the high-performance liquid chromatography method. Analysis of variance (ANOVA) was used to estimate analytical variation(CVA), within-subject BV(CVI) and between-subject BV(CVG). The individuality index (II) and reference change value (RCV) were calculated based on these data. The CVI of 25-OH D3, ferritin, folate, and vitamin B12 were found to be 1.8% (0.6%-2.5%), 16.9% (14.4%-20.2%), 10.7% (9.2%-12.7%), and 8.6% (6.8%-10.5%), respectively. CVG were 44.2% (34.3%-69.9%), 132% (87.7%-238%), 19.4% (14.4%-28.8%), and 39.6% (29.8%-59.0%) for the same biomarkers, while CVA were 3.2% (2.81%-3.71%), 3.5% (3.1%-4.1%), 4.0% (3.5%-4.6%), and 7.5% (6.6%-8.6%), respectively. The II values for 25-OH D3, ferritin, folate, and vitamin B12 were calculated as 0.04, 0.13, 0.55, and 0.22, respectively. The RCV were 10.2%, 47.8%, 31.7%, and 31.6%, respectively. Because the tests analyzed in this study exhibit high individuality, RCV should be preferred rather than population-based reference ranges in clinical interpretation of results.

What are the key success factors for strategy formulation and implementation? Perspectives of managers in the hotel industry.

This study investigates how hotel managers describe strategy and identify key success factors for its formulation and implementation. The study analyzes qualitative data collected through semi-structured interviews with property level top managers of hotels in Hong Kong. The findings show that hotel managers prioritize competition analysis and macro-environmental conditions over internal characteristics such as teamwork in strategy formulation. In the implementation phase, however, internal considerations such as employee involvement and strategic consensus are given prominence. This study provides a significant contribution by examining how top level practitioners in the industry interpret success factors in their strategic management efforts, and it highlights a largely neglected area in the hospitality and tourism management literature.

Strategy implementation research in hospitality and tourism: Current status and future potential.

To achieve their business objectives, hospitality and tourism organizations need effective implementation as well as consistent strategy formulation. However, the implementation aspect of strategy has attracted relatively less scholarly interest than strategic planning despite its critical role in achieving performance outcomes. Consequently, it is timely to provide an in-depth analysis of the strategy implementation literature. This is particularly the case in hospitality and tourism management where comprehensive literature reviews of strategy implementation have been lacking. To address the knowledge gap, the authors conduct a systematic literature review of 139 articles that appeared in 42 journals over the period 1988-2019. The items were grouped into six topic clusters with a view to generating novel research questions that have the potential to advance the field. We identify four main gaps that should be addressed and suggest prospective research directions.

Assessment of average of normals (AON) procedure for outlier-free datasets including qualitative values below limit of detection (LoD): an application within tumor markers such as CA 15-3, CA 125, and CA 19-9.

Average of normals (AON) is a quality control procedure that is sensitive only to systematic errors that can occur in an analytical process in which patient test results are used. The aim of this study was to develop an alternative model in order to apply the AON quality control procedure to datasets that include qualitative values below limit of detection (LoD). The reported patient test results for tumor markers, such as CA 15-3, CA 125, and CA 19-9, analyzed by two instruments, were retrieved from the information system over a period of 5 months, using the calibrator and control materials with the same lot numbers. The median as a measure of central tendency and the median absolute deviation (MAD) as a measure of dispersion were used for the complementary model of AON quality control procedure. The ubias values, which were determined for the bias component of the measurement uncertainty, were partially linked to the percentages of the daily median values of the test results that fall within the control limits. The results for these tumor markers, in which lower limits of reference intervals are not medically important for clinical diagnosis and management, showed that the AON quality control procedure, using the MAD around the median, can be applied for datasets including qualitative values below LoD.

Kidney Injury Molecule Levels in Type 2 Diabetes Mellitus.

BACKGROUND: This study was designed to determine the diagnostic role of urinary kidney injury molecule (KIM)-1 levels in renal damage in patients with type 2 diabetes mellitus according to the urinary albumin/creatinine ratio. METHODS: Patients with type 2 diabetes mellitus admitted to different polyclinics in our hospital enrolled in the study and were subdivided into three groups according to albumin/creatinine ratio - normalbuminuric (n: 20); microalbuminuric (n: 20); albuminuric (n: 18) - and compared with the control group. Urine albumin was analyzed using the immunoturbidimetric method (Architect C16000, Abbott Diagnostics). uKIM-1 was determined using a commercially available enzyme-linked immunosorbent assay test kit (USCN Life Science, Hankou, Wuhan, China). One-sample Kolmogorov-Smirnov test, Spearman correlation and Kruskal-Wallis non-parametric tests were performed. Post hoc comparisons were made using Bonferroni-corrected Mann-Whitney U tests. RESULTS: The differences between the controls and normalbuminuric, microalbuminuric and albuminuric groups were highly significant for KIM-1. Positive correlation was found between KIM-1 and urine microalbumin-urine microalbumin/creatinine (r = 0.479 P < 0.001; r = 0. 400, P < 0.001; respectively). CONCLUSION: In our study, KIM-1 levels were significantly different suggesting that urinary KIM-1 levels may be an early marker in patients with diabetic nephropathy. J. Clin. Lab. Anal. 00:1-6, 2016.

Monitoring the response to treatment of acute heart failure patients by ultrasonographic inferior vena cava collapsibility index.

OBJECTIVE: Our aim was to determine if N-terminal pro-brain natriuretic peptide (NT-proBNP) or sonographic measurements of inferior vena caval (IVC) diameters and collapsibility index (IVC-CI) have a role in the monitoring of acute heart failure (AHF) therapy. METHODS: Inferior vena caval diameters of 50 healthy people (control group) were measured to determine the normal values of the IVC parameters. We then prospectively enrolled patients who were admitted to the emergency department (ED) with a primary diagnosis of AHF. At presentation, IVC diameters were measured during expiration and inspiration, and blood was drawn for NT-proBNP. We repeated the measurement of the IVC parameters and collected a second blood sample 12 hours after the therapy was administered. The data were analyzed in SPSS 15.0 (IBM, Armonk, NY) using the Student t test and Mann-Whitney U test. RESULTS: A total of 97 subjects were enrolled: 47 in the patient group and 50 in the control group. The mean IVC during expiration was 2.10 ± 0.37 cm before and 1.57 ± 0.24 cm after the therapy (P < .001). The mean IVC during inspiration was 1.63 ± 0.40 cm before and 0.90 ± 0.26 cm after the therapy (P < .001). The mean IVC-CI rose from 22.80% ± 10.97% to 43.09% ± 13.63% (P < .001). After the therapy, there was no difference between the IVC-CI of the patients and controls (P = .246). There was no significant change in the mean NT-proBNP levels after the therapy. CONCLUSION: Inferior vena caval collapsibility index may be helpful in monitoring AHF patients' responses to therapy in the ED.

Vitamin D and vitamin D binding protein levels in COVID-19 intensive care unit patients: A prospective multicenter study.

Background: Vitamin D binding protein plays a crucial role in regulating vitamin D levels by carrying vitamin D and its metabolites and immunological response by binding to endotoxins and fatty acids. We aimed to compare vitamin D, DBP, and specific inflammatory markers among intensive care unit (ICU) patients with and without the COVID19 virus. Methods: This multicenter study in two training and research hospitals included 37 (13 female) COVID-19positive and 51 (34 female) COVID-19-negative ICU patients. 25(OH) vitamin D, DBP, C-reactive protein (CRP), procalcitonin (PCT), D-dimer, troponin T (TnT), interleukin 6 (IL-6) and ferritin levels, survival, mortality rates, duration of stay (ICU) were examined. Results: We observed higher ferritin and CRP levels, along with lower DBP, TnT, and D-dimer levels, in patients with COVID-19. ICU patients with COVID-19 exhibited elevated mortality rates (Odds Ratio: 3.012, 95% Confidence Interval (1.252-7.248), p=0.013). However, no statistically significant correlation was observed between mortality rates and Vitamin D or DBP levels across the ICU patient cohort. Conclusions: Vitamin D values were found to be low in all intensive care patients, regardless of their COVID-19 status. Contrary to the literature, COVID-19 patients had lower D-dimer and TNT levels than negative controls. However, COVID-19-positive ICU patients have decreased DBP. Further, DBP gene polymorphism studies are needed to explain this situation.

Predictors and outcomes of conversion to sternotomy in minimally invasive coronary artery bypass grafting.

Background: This study aims to investigate the risk factors and surgical outcomes of conversion to median sternotomy in minimally invasive direct coronary artery bypass grafting. Methods: Between January 2017 and July 2022, a total of 274 patients (246 males, 28 females; mean age: 57.0±9.6 years; range, 33 to 81 years) who underwent conventional (n=116) or robot-assisted (n=158) minimally invasive direct coronary artery bypass grafting were retrospectively analyzed. The primary outcome measure of the study was conversion to median sternotomy, and the secondary outcome measures were operative mortality, length of intensive care unit and hospital stay. Results: Conversion to median sternotomy was required in 26 (9.5%) patients. The most common cause of conversion was intramyocardial left anterior descending artery (27.0%). Among preoperative and operative characteristics, only age was statistically significant risk factor for conversion to sternotomy (odds ratio=1.06, p=0.01). Operative mortality occurred in one patient (0.36%) patient in the entire cohort. The length of intensive care unit and hospital stay was significantly longer in patients requiring conversion to median sternotomy (p=0.002 and p<0.001, respectively). There was no significant difference in other postoperative outcomes between the two groups (p>0.05). Conclusion: Intramyocardial left anterior descending artery is the most common reason for conversion to sternotomy, and older age increases the risk of conversion. Minimally invasive coronary artery bypass grafting can be performed with satisfactory results, even if it requires conversion to sternotomy.

Effect of epidural anesthesia on anastomotic leakage in colonic surgery: experimental study.

BACKGROUND: The association between the infusion of continuous epidural anesthesia and the anastomotic strength of colonic anastomosis was examined in an animal model. METHODS: Fourteen white male New Zealand rabbits were included in the study and randomly assigned to two groups. Group 1 (n=7) had continuous epidural 0.9% NaCl infusion (0.4 ml kg-1 bolus and 0.2 ml kg-1 h-1 infusion) and Group 2 (n=7) had continuous epidural 1% lidocaine infusion (0.4 ml kg-1 bolus and 0.2 ml kg-1 h-1 infusion). Infusions started at the beginning of the operation and were continued for six hours postoperatively. All experimental animals underwent right colon resection and colo-colonic anastomosis under general anesthesia. On the fourth postoperative day, relaparotomy was applied and the bursting pressures of the anastomosis (BPA) were measured in situ. Segments 1-cm long consisting of the complete suture lines were excised, and the levels of hydroxyproline and collagen were measured. RESULTS: BPAs were statistically higher in the epidural lidocaine group (median: 248 mmHg; min 117 - max 300) than in the saline group (median: 109 mmHg; min 47 - max 176) (p=0.006). There was no difference between the groups in terms of hydroxyproline and collagen levels in the sample tissues (p>0.05). CONCLUSION: We concluded that the strength of colonic anastomosis may be increased by epidural lidocaine infusion.

Detection of preanalytical errors in arterial blood gas analysis.

Introduction: Blood gas analysis (BGA) is an essential test used for years to provide vital information in critically ill patients. However, the instability of the blood gases is a problem. We aimed to evaluate time and temperature effects on blood gas stability. Materials and methods: Arterial blood was collected from 20 patients into syringes. Following BGA for baseline, syringes were divided into groups to stand at 4°C and 22°C for 30, 60, 90, 120 minutes. All were tested for pH, partial pressure of carbon dioxide (pCO2), partial pressure of oxygen (pO2), oxygen saturation (sO2), oxyhemoglobin (O2Hb), sodium, potassium, glucose, lactate, oxygen tension at 50% hemoglobin saturation (p50), and bicarbonate. A subgroup analysis was performed to detect the effect of air on results during storage. Percentage deviations were calculated and compared against the preset quality specifications for allowable total error. Results: At 4°C, pO2 was the least stable parameter. At 22°C, pO2 remained stable for 120 min, pH and glucose for 90 min, lactate and pCO2 for 60 min. Glucose and lactate were stable when chilled. Air bubbles interfered pO2 regardless of temperatures, whereas pCO2 increased significantly at 22°C after 30 min, and pH decreased after 90 min. Bicarbonate, sO2, O2Hb, sodium, and potassium were the unaffected parameters. Conclusions: Correct BGA results are essential, and arterial sample is precious. Therefore, if immediate analysis cannot be performed, up to one hour, syringes stored at room temperature will give reliable results when care is taken to minimize air within the blood gas specimen.

Barriers To Strategy Implementation In Turkey's Healthcare Industry: Hospital Manager Perspectives.

Although strategy implementation has profound implications for delivering efficient service, it has been largely neglected in the healthcare management literature. This study explores the barriers to effective implementation of strategic plans in healthcare organizations. To achieve this end, empirical data were collected from 185 hospital managers in Turkey using a survey-based methodology. A descriptive analysis was undertaken of the survey responses to determine the most important barriers to strategy implementation. The most significant barriers undermining strategy implementation efforts were found to be: low employee motivation, an exclusive focus on financial performance and lack of consensus among decision makers.

The Promise and Perils of Compound Discovery Screening with Inducible Pluripotent Cell-Derived Neurons.

Neurological diseases comprise more than a thousand ailments that adversely affect the brain and nervous system. When grouped together, these neurological conditions impact an estimated 100 million individuals in the United States and up to a billion people worldwide, making drug discovery efforts imperative. However, recent research and development efforts for these neurological diseases, including Alzheimer's disease and amyotrophic lateral sclerosis, have been exceedingly disappointing and typify the challenges associated with translating in vitro and cell-based discoveries to successful preclinical models and subsequent human clinical trials. Our viewpoint is that neuronal progenitor cells and neurons derived from inducible pluripotent stem cells afford an innovative translational bridge, with higher pathological relevancy than previous cellular models. We outline some of the opportunities and challenges associated with their evolving usage in drug discovery and development.

A three-dimensional dementia model reveals spontaneous cell cycle re-entry and a senescence-associated secretory phenotype.

A hexanucleotide repeat expansion on chromosome 9 open reading frame 72 (C9orf72) is associated with familial amyotrophic lateral sclerosis (ALS) and a subpopulation of patients with sporadic ALS and frontotemporal dementia. We used inducible pluripotent stem cells from neurotypic and C9orf72+ (C9+) ALS patients to derive neuronal progenitor cells. We demonstrated that C9+ and neurotypic neuronal progenitor cells differentiate into neurons. The C9+ neurons, however, spontaneously re-expressed cyclin D1 after 12 weeks, suggesting cell cycle re-engagement. Gene profiling revealed significant increases in senescence-associated genes in C9+ neurons. Moreover, C9+ neurons expressed high levels of mRNA for CXCL8, a chemokine overexpressed by senescent cells, while media from C9+ neurons contained significant levels of CXCL8, CXCL1, IL13, IP10, CX3CL1, and reactive oxygen species, which are components of the senescence-associated secretory phenotype. Thus, re-engagement of cell cycle-associated proteins and a senescence-associated secretory phenotype could be fundamental components of neuronal dysfunction in ALS and frontotemporal dementia.

Evaluation of insulin resistance in normoglycemic patients with coronary artery disease.

BACKGROUND: Insulin resistance is clearly associated with coronary artery disease (CAD) in diabetics. Insulin resistance may also be present in normoglycemic individuals, and some of these patients can be diagnosed as having metabolic syndrome (MS) according to various definitions. However, the relationship between hyperinsulinemia and CAD is obscure in normoglycemic individuals, especially in patients who do not meet the criteria for MS. HYPOTHESIS: This study evaluated insulin resistance in normoglycemic patients with CAD, and investigated the association of insulin resistance with inflammation and lipid levels. METHODS: Fifty-six CAD patients, and 57 age- and sex-matched controls with normal coronary arteries confirmed by conventional coronary arteries angiography were included in the study. Participants were considered for the diagnosis of MS according to criteria of the National Cholesterol Education Program (NCEPATP III) and the International Diabetes Federation (IDF). Fasting plasma glucose, insulin, lipids, and c-reactive protein (CRP) levels were studied. The homeostasis model assessment insulin resistance index (HOMA IR) was calculated. RESULTS: The ratio of subjects with MS was similar in the 2 groups. Insulin, CRP, low-density lipoprotein (LDL) cholesterol, and HOMA IR were higher in the study group than in the controls. The HOMA IR, LDL cholesterol, and serum CRP levels were determined as predictors of CAD. CONCLUSION: Our data revealed that insulin resistance and subclinical inflammation are present in normoglycemic patients with CAD. As the proportion of patients with MS was similar in the 2 groups, we suggest that HOMA IR values may provide more sensitive information than MS definitions about the association between insulin resistance and CAD in normoglycemic patients.

The renal effect of replacement fluids in controlled severe hemorrhagic shock: an experimental study.

BACKGROUND: This experimental study examined the effects of resuscitation with Ringer's lactate (RL), 6% hydroxyethyl starch (130/0.4-HES), and the combination of RL and HES on renal function in hemorrhagic shock (HS). METHODS: Twenty-four male New Zealand white rabbits weighing 2198-3435 g were divided at random into four groups. HS was constituted by maintaining the mean arterial blood pressure at 30 mmHg and blood lactate at >4 mM/L. Subsequently, Group 1 (control) was not resuscitated, while the study rabbits' resuscitation was initiated with RL (Group 2), HES (Group 3), or the combination of RL and HES (Group 4). RESULTS: In all groups, the serum creatinine and blood urea nitrogen (BUN) levels were observed to be within normal limits, while the lactate dehydrogenase and alpha-1 microglobulin levels statistically significantly increased when time points were compared with beginning values (p<0.05). Furthermore, cystatin-C levels were observed to be increased after the HS (p<0.05), but returned to the normal level after resuscitation in all the study groups. Interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha levels were increased in all the rabbits after HS (p<0.05), and there were no significant differences among the study groups after resuscitation (p>0.05). There were no differences in the histological imaging between the groups (p>0.05). CONCLUSION: The 6% HES (130/0.4) did not have any harmful effects on the kidney when it was used alone or in combination with crystalloid for resuscitation of HS in rabbits.

Additive prognostic value of NT-proBNP over TIMI risk score in intermediate-risk patients with acute coronary syndrome.

OBJECTIVES: We evaluated the prognostic value of N-terminal pro-brain natriuretic peptide (NT-proBNP) for further risk stratification of intermediate-risk patients with non-ST elevation acute coronary syndromes (NSTE-ACS). STUDY DESIGN: The study included 137 intermediate-risk patients (85 men, 52 women; mean age 62+/-11 years) with ACS, based on the TIMI risk score (scores 3 to 5). Serum NT-proBNP levels were measured 12 hours after the last anginal episode. The patients were divided into four groups according to the following NT-proBNP quartiles: 17-310 pg/ml (n=34), 313-688 pg/ml (n=35), 724-2,407 pg/ml (n=34), and 2,575-24,737 pg/ml (n=34). Primary endpoint of the study was mortality. The mean follow-up was 21.8+/-7.1 months. RESULTS: There were 27 deaths (19.7%), 14 of which were in the 4th quartile (4th vs 1st, 2nd, and 3rd quartiles: p=0.02, p=0.01, and p<0.01, respectively). The first three quartiles did not differ significantly in this respect. In Kaplan-Meier analysis, patients in the 4th quartile had the lowest cumulative survival (log rank test, 4th vs 1st, 2nd, and 3rd quartiles: p=0.041, p=0.026, and p=0.009, respectively). NT-proBNP level was significantly higher in nonsurvivors than in survivors (p=0.01). In univariate analysis, mortality was also associated with the TIMI risk score, ejection fraction, and age. Patients who died were older (65.6+/-11.9 years vs 60.7+/-11.0 years; p=0.048) and had a lower ejection fraction (46.3+/-11% vs 54.1+/-9.8%; p<0.001) than patients who survived. Mortality rates corresponding to TIMI risk scores of 3, 4, and 5 were 25.9%, 29.6%, and 44.4%, respectively (p=0.58 for TIMI 3 vs 4; p=0.001 for TIMI 3 vs 5; p=0.013 for TIMI 4 vs 5). Cox proportional hazards regression analysis showed that only TIMI risk score was an independent predictor of mortality (hazard ratio 2.3, 95% confidence interval 1.4-3.8, p=0.001). CONCLUSION: NT-proBNP has an additive predictive value over TIMI risk score in predicting long-term mortality in intermediate-risk patients with ACS.

Aberrant Neuronal Cell Cycle Re-Entry: The Pathological Confluence of Alzheimer's Disease and Brain Insulin Resistance, and Its Relation to Cancer.

Aberrant neuronal cell cycle re-entry (CCR) is a phenomenon that precedes and may mechanistically lead to a majority of the neuronal loss observed in Alzheimer's disease (AD). Recent developments concerning the regulation of aberrant neuronal CCR in AD suggest that there are potential intracellular signaling "hotspots" in AD, cancer, and brain insulin resistance, the latter of which is characteristically associated with AD. Critically, these common signaling nodes across different human diseases may represent currently untapped therapeutic opportunities for AD. Specifically, repurposing of existing US Food and Drug Administration-approved pharmacological agents, including experimental therapeutics that target the cell cycle in cancer, may be an innovative avenue for future AD-directed drug discovery and development. In this review we discuss overlapping aspects of AD, cancer, and brain insulin resistance from the perspective of neuronal CCR, and consider strategies to exploit them for prevention or therapeutic intervention of AD.

Serum hyaluronan levels in patients with knee osteoarthritis.

We examined the association between clinical parameters of disease activity and serum hyaluronic acid (HA) level in patients with knee osteoarthritis (OA). Fifty-eight patients with knee OA and 40 healthy individuals were included in this study. Demographic data were noted. The radiological evaluation was done according to Kellgren/Lawrence Grading System. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) was used in evaluating the clinical disability caused by OA. Erythrocyte sedimentation rate (ESR) and serum C-reactive protein (CRP) level were determined in laboratory evaluations. Serum HA levels (in nanogram per milliliter) of both groups were measured by enzyme-linked immunosorbent assay. The mean ages of patients in OA group and control group were 57.58 (9.55) and 43.3(10.2) years, respectively. There was a significant difference between HA levels of both groups (p=0.02). Also, there was a significant correlation between HA level and disease duration (p=0.04), ESR (p=0.001), and CRP level (p<0.001). However, there was no significant correlation between HA levels with WOMAC and radiological grade (p>0.05). There is no satisfactory amount of data regarding HA level in OA. In our study, we demonstrated that HA was in high levels in the serum of patients with OA. We suggest that serum HA levels may be used as a marker to determine the disease activity.