bluuebunny/crossref_metadata_2025 huggingface dataset:
Adipokines in Patients with Cancer Anorexia and Cachexia
Authors: Smiechowska Joanna , Utech Anne , Taffet George , Hayes Teresa , Marcelli Marco , Garcia José M.
Published: May 2016

Background

Anorexia, cachexia, and insulin resistance are commonly seen in patients with cancer. Adipocyte-derived hormones or adipokines play a role in the regulation of appetite, body weight, and insulin sensitivity. However, their role in cancer-induced cachexia has not been well-established. The objective of this study was to determine the levels of adipokines and their relation to appetite, weight loss, insulin resistance, and other hormones in cancer cachexia.

Methods

We measured adiponectin, resistin, and leptin plasma levels in 21 men with cancer cachexia, 24 noncachectic cancer subjects, and 25 noncancer controls matched by age, sex, and pre-illness body weight. Body weight change, appetite scores, insulin resistance assessed by homeostasis model assessment, and other cytokines and hormones were also measured. Differences between groups were measured by analysis of covariance. Relations between variables were examined by linear regression analyses.

Results

Adiponectin levels were similarly elevated in cachectic and noncachectic cancer patients compared with noncancer controls. Leptin levels were significantly decreased in cancer cachexia and were directly associated with appetite and insulin resistance, explaining 37% and 19% of the variance seen in cancer patients, respectively. Resistin levels were not different between groups.

Conclusions

Leptin may play a role in the increased insulin resistance seen in cancer patients. However, these patients are resistant to the orexigenic effects of hypoleptinemia. Other mechanisms besides weight loss are responsible for the increased adiponectin level seen in cancer patients. It is unlikely that resistin plays a major metabolic role in this setting.
Optimum Timing of Blood Tests for Monitoring Patients with Clostridium difficile-Associated Diarrhea
Authors: Bhangu Aneel , Czapran Adam , Bhangu Sonia , Pillay Devadas
Published: May 2016

Objective

This study aimed to identify optimum timing of blood tests and suitable cutoff values when managing patients with Clostridium difficile-associated diarrhea (CDAD), in relation to early mortality.

Methods

Review of 204 patients treated as inpatients for a first episode of CDAD from January to December 2008. Differences in values during the first 7 days of CDAD for white cell count (WCC), albumin, C-reactive protein, and creatinine between those who died and survivors to 30 days were compared using Mann-Whitney U tests. Cutoff values were assessed using receiver operating characteristic curves.

Results

Overall 30-day mortality was 27% (n = 56/204). White cell counts were significantly higher in those who died on the first 3 days ( P < 0.001, P = 0.015, and P = 0.001, respectively). Median WCC in those who died was 20 × 109/L or greater on both days 1 and 2. Albumin was significantly different on day 1 only ( P = 0.003); C-reactive protein, and creatinine did not differ significantly on any day. The highest WCC in the first 3 days produced an area under the curve of 0.718 ( P < 0.001). A WCC cutoff at 20 × 109/L or greater when compared with 15 × 109 or greater had a higher positive predictive value (0.46 vs 0.34) and specificity (0.82 vs 0.60) but a lower sensitivity (0.49 vs 0.65). Mortality rates in the 2 groups were 46% and 34%, respectively.

Conclusions

White cell count in the first 3 days is the strongest serum predictor of mortality and should be routinely monitored. A WCC of 20 × 109/L or greater may be the best cutoff value to objectively identify cases at higher risk of death.
Left Ventricular Diastolic Function in Patients on Hemodialysis
Authors: Raizada Veena , Skipper Betty , Taylor Robert A. , Luo Wentao , Harford Antonia A. , Zager Philip G. , Rohrscheib Mark , Spalding Charles T.
Published: May 2016

Background

Previous studies have shown that the assessment of Doppler mitral flow velocity (DMFV) curves can be used to predict prognosis owing to left ventricular (LV) diastolic dysfunction in certain specific diseases. Our aim was to study whether the prognostic value of DMFV curves is affected by the many end-stage renal disease factors, such as chronic uremia and long-term hemodialysis (HD), which cause LV diastolic dysfunction and death.

Methods

Retrospective echo Doppler studies obtained 10 to 12 hours after HD in 90 patients (52 males; mean age, 56 years) were analyzed to determine changes in deceleration time (DT) of the early mitral filling wave ( E) and the ratio of E to the atrial velocity ( A). The study findings (n = 83) showed 2 groups of DT: long DT (DT > 240 milliseconds) and normal/short DT (DT ≤ 240 milliseconds). Continuous variables of LV size using internal dimensions, systolic function using ejection fraction, hypertrophy using wall thickness and mass, and pulmonary hypertension and E/ A were compared between the 2 groups.

Results

Patients with long DT versus normal/short DT had lower absolute and indexed LV mass ( P = 0.03 and P = 0.02, respectively) and pulmonary hypertension ( P ≤ 0.001), without a significant difference in LV systolic function or E/ A. The mortality rate, adjusted for age and sex, was lower with long DT versus normal/short DT, with a hazard ratio of death, 0.44 (95% confidence interval, 0.23-0.86, P = 0.02).

Conclusions

Our study identified characteristics of DMFV curves in patients on long-term HD, which are clearly of value in predicting outcomes and survival in these patients.
Faculty Involvement in Translational Research and Interdisciplinary Collaboration at a US Academic Medical Center
Authors: Weston Christine M. , Bass Eric B. , Ford Daniel E. , Segal Jodi B.
Published: May 2016

Background

Forty-six academic health centers have been awarded Clinical and Translational Science Awards by the National Institutes of Health to enhance health by advancing translational research.

Objective

As a recipient of a Clinical and Translational Science Award, we aimed to determine the prevalence of translational and interdisciplinary collaboration at our institution.

Design, Setting, and Participants

We surveyed all full-time faculty and postdoctoral fellows (n = 3870) in the Johns Hopkins Schools of Medicine, Public Health, Nursing and Engineering, in late 2008.

Main Outcome Measures

Outcomes included (1) the proportion of investigators involved in early (T1), late (T2), and reverse translational (RT) research; (2) barriers to translational research; (3) attitudes about translational research; (4) involvement in interdisciplinary collaboration; and (5) barriers to collaboration.

Results

With 1800 respondents, the response rate was 55% for faculty and 40% for postdoctoral fellows. Of the 1314 investigators with more than 30% of their time committed to research, 69% reported conducting 1 or more types of translational research (T1 = 79%, T2 = 36%, RT = 36%). Attitudes about translational research revealed both concern and uncertainty. Fifty-four percent of respondents described translational research as having complex regulatory requirements; 42% felt that an individual's contributions suffer from underrecognition, 39% described it as high risk, and 35% consider funding less secure for translational researchers. Collaboration across school and types of research was common. Forty-seven percent of basic scientists collaborated with a clinical investigator in the last year, and 56% of clinical investigators collaborated with a basic scientist.

Conclusions

Overall, investigators who did translational research reported a greater number of collaborators than those who did not.
Both Vascular Endothelial Growth Factor and Soluble Flt-1 are Increased in Type 2 Diabetes but not in Impaired Fasting Glucose
Authors: Nandy Debashis , Mukhopadhyay Debabrata , Basu Ananda
Published: May 2016

Objective

Inadequate vascular remodeling is contributory to increased cardiovascular events in people with type 2 diabetes mellitus (DM) and impaired fasting glucose (IFG). Vascular endothelial growth factor (VEGF) and its regulatory molecule soluble Flt-1(sFlt-1) play important roles in atherogenesis.

Research Design

We measured fasting plasma concentrations of VEGF and sFlt-1 in 11 nondiabetic (ND) (aged 46.1 ± 2.1 years; body mass index [BMI], 26.1 ± 0.9 kg/m2; glucose, 5.0 ± 0.1 mM), 15 IFG (aged 52.9 ± 1.8 years; BMI, 32.7 ± 1.3 kg/m2; glucose, 6.4 ± 0.1 mM), and 8 DM (aged 55.8 ± 3.2 years; BMI, 30.0 ± 1.0 kg/m2; glucose, 9.3 ± 0.5 mM) subjects.

Results

Plasma VEGF (42.1 ± 4.0 vs 24.2 ± 0.9 vs 29.4 ± 3.8 pg/mL, respectively) and sFlt-1 (119.4 ± 4.9 vs 58.9 ± 3.2 vs 56.7 ± 1.2 pg/mL, respectively) concentrations were higher ( P < 0.04) in DM than IFG and ND subjects. Whereas VEGF concentrations were significantly lower ( P < 0.05) in IFG than in ND subjects, sFlt-1 concentrations did not differ between the IFG and ND subjects.

Conclusions

Although plasma VEGF concentrations were higher (35%) in DM than in ND subjects, VEGF action on vascular remodeling was likely attenuated by higher sFlt-1 concentrations in DM. In contrast, IFG subjects did not have major perturbations in either VEGF or sFlt-1 levels. Further studies defining the roles of these mediators in DM and IFG are necessary to extend these observations.
Promises and Pitfalls in Erythopoietin-Mediated Tissue Protection: Are Nonerythropoietic Derivatives a Way Forward?
Authors: Hand Carla Cerami , Brines Michael
Published: May 2016

The essential biological role of erythropoietin (EPO) in maintaining erythrocyte mass has been well understood for many years. Although EPO is required for the maturation of red cells, it also has strong procoagulant effects on the vascular endothelium and platelets, which limit erythrocyte losses after hemorrhage. Like other members of the type 1 cytokine superfamily, EPO has multiple biological activities. For the past 10 years, multiple investigators have shown that EPO acts as a locally produced antagonist of proinflammatory cytokines that are generated by the innate immune response in response to infection, trauma, or metabolic stress. Specifically, EPO inhibits apoptosis of cells surrounding a locus of injury, reduces the influx of inflammatory cells, and recruits tissue-specific stem cells and endothelial progenitor cells. Available evidence suggests that these multiple, nonerythropoietic effects of EPO are mediated by a tissue protective receptor (TPR) that is distinct from the homodimeric receptor responsible for erythropoiesis. Notably, activation of the TPR requires a higher concentration of EPO than is needed for maximal erythropoiesis. Unfortunately, these higher concentrations of EPO also stimulate hematopoietic and procoagulant pathways, which can cause adverse effects and, therefore, potentially limit the clinical use of EPO for tissue protection. To circumvent these problems, the EPO molecule has been successfully modified in a variety of ways to interact only with the TPR. Early clinical experience has shown that these compounds appear to be safe, and proof of concept trials are ready to begin.
7-Year Survey after Percutaneous Dilatational Tracheotomy on a Medical Intensive Care Unit
Authors: Lebiedz Pia , Suca Annemarie , Gümüs Emel , Radke Robert M. , Kaya Elif , Hilker Ekkehard , Reinecke Holger
Published: May 2016

Purpose

Percutaneous dilatational tracheotomy (PDT) is a well-established procedure in intensive care medicine. Several reports confirm a low acute and long-term complication rate. However, dilatational tracheotomy is still often postponed even in patients that are under ventilator support for more than 2 weeks. We present a retrospective study analyzing the subjective long-term results after percutaneous tracheotomy performed at our medical intensive care unit between 2002 and 2008.

Methods

We used a modified method described by Ciaglia for tracheotomy. We selected 649 patients eligible for the survey among those who had received PDT between 2002 and 2008 and had been dismissed from hospital alive.

Results

The return rate was 38.5% with 29.8% of the questionnaires being completed by the patients; in 32 cases, relatives reported of the patients' death. No patient experienced wound infection; none needed surgical wound revision. Dysarthria was reversible in all 16 cases; 2 patients reported a persistent hoarseness that was preexisting in both cases. One patient experienced a tracheal stenosis and received a tracheal stent; one other required a permanent tracheotomy because of a nonresectable granulation tissue. The overall rate of long-term complications associated with the long-term ventilation and the PDT was 1.8%.

Conclusions

Percutaneous dilatational tracheotomy is an easily performed, cost-saving method for long-term ventilated patients with a low rate of acute and long-term complications even in old and multimorbid internal medicine patients.
“Senobi” Stretch Ameliorates Asthma Symptoms by Restoring Autonomic Nervous System Balance
Authors: Sato Kazunari , Kawamura Toshihiko , Abo Toru
Published: May 2016

The number of asthmatic patients is increasing in Japan. It is conceivable that changes in lifestyle (eg, lack of exercise and high-energy diet) may be associated with this phenomenon. The resulting factor seems to be altered activity of autonomic nervous system of these patients. When this activity was estimated by the measurement of heart rate variability, asthmatic patients (n = 11) showed a tendency for parasympathetic nerve dominance in comparison with healthy controls (n = 10). We recommend the patients engage in the “Senobi” stretch exercise, which involves stretching the arms and body upward while standing. After 1 month of regularly performing this exercise, most patients showed a decrease in the frequency of asthma rescue medication use. They also showed a recovery of forced expiratory volume in 1 second. These results suggest that the Senobi stretch is a useful exercise for asthmatic patients to perform to achieve a desirable improvement in symptoms.
Effective Antihypertensive Strategies for High-Risk Patients with Diabetic Nephropathy
Authors: Van Buren Peter Noel , Adams-Huet Beverley , Toto Robert Daniel
Published: May 2016

Aim

Clinical guidelines recommend blood pressure (BP) lowering and renin-angiotensin-aldosterone system inhibition to slow kidney disease progression in patients with diabetic nephropathy. This study's purpose was to determine whether an antihypertensive regimen including a maximally dosed angiotensin-converting enzyme inhibitor could safely achieve target BP in indigent, predominantly minority patients with this disease.

Methods

We studied 81 hypertensive adults (52% Hispanic and 31% African American) with nephropathy attributed to type 1 or 2 diabetes during the run-in period of a randomized controlled trial. The subjects received lisinopril titrated to 80 mg daily and additional antihypertensives to target a systolic BP (SBP) lower than 130 mm Hg. Blood pressure and serum potassium level were measured weekly, and a 4-gram sodium diet was prescribed. The primary outcome variable was SBP change from screening to randomization. Success in achieving SBP goal, change in urine albumin-creatinine ratio, hyperkalemia (serum potassium ≥5.5 mmol/L) and hypotension (SBP < 100 mm Hg) were also analyzed.

Results

The median SBP decreased from 144 to 133 mm Hg (median change, −9.6%.) Fifty-eight (71%) achieved goal SBP during run-in. The median UACR decreased from 206.8 to 112.7 mg/mmol (median change, −42.7%). The UACR reduction correlated with SBP reduction. Seventeen subjects experienced hyperkalemia responsive to dietary/medical management. Two subjects experienced hypotension responsive to medication adjustments.

Conclusion

A regimen using a maximally dosed angiotensin-converting enzyme inhibitor is safe and effective for achieving BP goal in high-risk, predominantly minority patients with diabetic nephropathy. Implementing this regimen necessitates close monitoring of serum potassium level.
Screening for the Metabolic Syndrome in a Public Care Hospital Clinic Population a Simple Measurement of Waist Circumference
Authors: Parish Roy C. , Huang Jian , Mansi Ishak
Published: May 2016

Background

Metabolic syndrome is a collection of anthropomorphic and metabolic derangements that, taken together, constitute a strong predictor of stroke, cardiovascular disease, type 2 diabetes, and perhaps other disorders. Diagnosing the metabolic syndrome according to presently accepted definitions requires a mixture of anthropomorphic and laboratory measurements. In indigent patient populations or locations that lack adequate laboratory facilities, a noninvasive low-cost or cost-free alternative would be beneficial as a preliminary screening measure.

Methods

To identify potential means for the diagnosis, we evaluated anthropomorphic measures individually and in combination for their predictive value against the standard classification. Receiver operator characteristic curves identified optimal cutoff values for the variables tested, and consideration of sensitivity and specificity were considered concerning the consequences of false negatives and positives.

Results

Receiver operator characteristic curves showed that only waist circumference in men gave acceptable specificity and sensitivity. Combinations of measurements did not improve on a simple measurement of waist circumference.

Conclusions

Waist circumference was a potentially useful single indicator in men but not in women. Other values and combinations were evaluated as well. Waist measurement alone may serve as sufficient screening in men in locations where laboratory facilities are lacking or funds are severely limited, as in developing countries.
Evidence that Androgens Modulate Human Thymic T Cell Output
Authors: Olsen Nancy J. , Kovacs William J.
Published: May 2016

Background

The thymus has long been recognized as a target for the actions of androgenic hormones, but it has only been recently recognized that alterations in circulating levels of gonadal steroids might affect thymic output of T cells. We had the opportunity to examine parameters of thymic cellular output in several hypogonadal men undergoing androgen replacement therapy.

Methods

Circulating naive (CD4+CD45RA+) T cells were quantitated by flow cytometric analysis of peripheral blood mononuclear cells. Cells bearing T-cell receptor excision circles were quantitated using real-time polymerase chain reaction amplification of DNA isolated from peripheral blood mononuclear cells from healthy men and from hypogonadal men before and after testosterone replacement therapy.

Results

CD4+CD45+ (naive) T cells comprised 10.5% of lymphocytes in healthy males; this proportion was greatly increased in 2 hypogonadal men (35.5% and 44.4%). One man was studied sequentially during treatment with physiologic doses of testosterone. CD4+CD45RA+ cells fell from 37.36% to 20.05% after 1 month and to 12.51% after 7 months of normalized androgen levels. In 2 hypogonadal patients, T-cell receptor excision circle levels fell by 83% and 78% after androgen replacement therapy.

Conclusions

Our observations indicate that the hypogonadal state is associated with increased thymic output of T cells and that this increase in recent thymic emigrants in peripheral blood is reversed by androgen replacement.
Familial Pycnodysostosis: Identification of a Novel Mutation in the CTSK Gene (Cathepsin K)
Authors: Toral-López Jaime , Gonzalez-Huerta Luz Maria , Sosa Blanca , Orozco Sócrates , González Hugo Peláez , Cuevas-Covarrubias Sergio A.
Published: May 2016

Background

Pycnodysostosis, an autosomal recessive skeletal dysplasia, is characterized by short stature, osteosclerosis, delayed cranial suture closure, hypoplastic mandible, acro-osteolysis, hypoplastic clavicle, and dental anomalies. The disorder is caused by CTSK gene defects, a gene localized on 1q21.

Purpose

To describe the clinical, radiological, and molecular findings in a family with pycnodysostosis.

Methods

The CTSK gene was analyzed from genomic DNA in a nonconsanguinity Mexican family with 3 affected members with pycnodysostosis and 100 healthy controls.

Results and Interpretation

We identified the novel homozygous mutation c.908G>A within exon 8 of the CTSK gene. This missense mutation leads to the substitution of the amino acid glycine at position 303 by glutamic acid (G303E) in cathepsin K protease. No genotype/phenotype correlation was present in affected members of the family with pycnodysostosis.
Lack of Association between the IL-10 Gene Polymorphisms and Features of the Metabolic Syndrome
Authors: Lu Ming-Ying , Lakkakula Bhaskar V.K.S. , Liao Yi-Chu , Tsai Pei-Chien , Yang Yi-Hsin , Juo Suh-Hang Hank
Published: May 2016

Backgrounds

Insulin resistance plays a major role in the pathogenesis of the metabolic syndrome. Inflammation is the leading cause of insulin resistance, and interleukin 10 (IL-10) is one of the anti-inflammatory cytokines. We conducted a case-control study to investigate the association between the IL-10 polymorphisms and the metabolic syndrome.

Methods

One thousand two hundred two unrelated subjects residing in southern Taiwan were retrospectively recruited from a community-based health screening program. Two hundred sixty subjects were defined as the metabolic syndrome (3-5 risk components) and 549 subjects as controls (0-1 risk component) on the basis of the Asian version of the Adult Treatment Panel III criteria. A functional IL-10 single nucleotide polymorphism (SNP; rs1800871) and 2 tagging SNPs (rs3790622, rs3021094) were genotyped by TaqMan method.

Results

We analyzed the association between the genotypes and the presence of the metabolic syndrome or metabolic traits by χ2 test and multivariant logistic regression. None of the IL-10 SNPs were found to be significantly related with the metabolic syndrome or its risk components. All the 3 SNPs were in single linkage disequilibrium block. Haplotype analysis did not yield significant association between IL-10 gene and the metabolic syndrome (global P = 0.88).

Conclusions

Because we used tagging SNPs and a modest clinical cohort, we concluded that the IL-10 gene polymorphisms may be unlikely to play an important role for the metabolic syndrome.
Inhibitory Effect of Dexamethasone on Arginine-Vasopressin Release Induced by Physical Exercise in Man
Authors: Coiro Vittorio , Volpi Riccardo , Volta Elio , Melani Andrea , Maffei Maria Ludovica , Chiodera Paolo
Published: May 2016

To establish whether glucocorticoids inhibit the arginine-vasopressin (AVP) response to physical exercise, 10 healthy men underwent bicycle ergometer tests until exhaustion (exercise control test, exercise plus dexamethasone [2 or 4 mg in an intravenous bolus]). Physiological and biochemical variables were similar in all tests. Pretreatment with dexamethasone (2 or 4 mg) partially but significantly decreased the AVP response induced by physical exercise. Our results demonstrate a partial inhibition induced by glucocorticoids of AVP neurosecretion during cycle ergometer tests.
Vascular Endothelial Growth Factor Gene Polymorphisms and Rheumatoid Arthritis
Authors: Lv Hao-zhe , Lin Tao , Xia Li-ping , Shen Hui , Zhu Xiang-yang , Zhang Jin-tao , Xiao Wei-guo , Lu Jing
Published: May 2016

Objective

To investigate polymorphisms of the vascular endothelial growth factor (VEGF) gene in patients with rheumatoid arthritis (RA) and their relationship to clinical features.

Method

A total of 198 unrelated Chinese individuals were enrolled in this study, including 98 patients with RA and 100 healthy controls. Eight different polymorphisms of the VEGF gene were analyzed using Sequenom MassArray platform.

Result

All 8 polymorphisms were in Hardy-Weinberg equilibrium in controls. The frequencies of rs833070 A allele and rs325010 C allele were elevated in the patients with RA compared with the controls. There were increased genotype frequencies in GA of rs833070, GC of rs3025030, CT of rs3025039 and decreased genotype frequencies in GG of rs833070, GG of rs3025030, CC of rs3025039 in the patients with RA compared with the controls. The frequencies of haplotype GA in rs2010963 and rs833070 were higher in the patients with RA than in the controls. There was no significant difference in the genotype or allele frequencies in the RA group sorted by complications, serum markers, or age of onset.

Conclusion

Our data suggested a trend of association between VEGF gene polymorphisms and RA, and patients who carried the haplotype GA of rs2010963 and rs833070 were more susceptible to RA. Our study was performed in a small population, and further studies in other populations are needed to confirm these results.
Association among Microalbuminuria and Oxidative Stress Biomarkers in Patients with Type 2 Diabetes
Authors: Vicentini Juliana , Valentini Juliana , Grotto Denise , Paniz Clóvis , Roehrs Miguel , Brucker Natália , Charão Mariele F. , Moro Angela M. , Tonello Raquel , Moreira Ana Paula L. , Buffon Andréia , Beck Maristela , Garcia Solange Cristina
Published: May 2016

Aim

Hyperglycemia in diabetes mellitus (DM) may be one of the most important factors responsible for the development of oxidative stress, which promotes the main complications in DM patients. Therefore, this study evaluated if the hyperglycemia could be related to oxidative stress biomarkers, lipid profile, and renal function in type 2 diabetes patients without clinic complications.

Methods

Plasmatic malondialdehyde (MDA), serum protein carbonyl (PCO), serum creatinine levels, microalbuminuria, glycated hemoglobin, and lipid profile were analyzed in 37 type 2 diabetic patients and 25 subjects with no diabetes.

Results

Serum creatinine levels were within the reference values, but microalbuminuria presented increased levels in all the patients compared with controls ( P < 0.05) and above of the reference values. The MDA, PCO, low-density lipoprotein, and triglyceride levels showed positive correlation with microalbuminuria levels. Moreover, glycated hemoglobin presented positive correlation with MDA, PCO, and microalbuminuria levels.

Conclusions

The hyperglycemia could be responsible for the increase of the microalbuminuria levels and for the oxidation process in lipids and proteins in DM patients. Therefore, we suggested that the microvascular lesion is a direct consequence from hyperglycemia and an indirect one from the increased oxidative stress. Malondialdehyde and protein carbonyl levels could be suggested as additional biochemical evaluation to verify tissue damage in type 2 DM patients.
Ethics and Technology Transfer: Patients, Patents, and Public Trust
Authors: Zucker Deborah
Published: May 2016

Universities and academic medical centers have been increasing their focus on technology transfer and research commercialization. With this shift in focus, academic-industry ties have become prevalent. These relationships can benefit academic researchers and help then to transform their research into tangible societal benefits. However, there also are concerns that these ties and the greater academic focus on commercialization might lead to conflicts of interest, especially financial conflicts of interest. This paper briefly explores some of these conflicts of interest, particularly relating to research and training. This paper also discusses some of the policies that have been, and are being, developed to try to mitigate and manage these conflicts so that academic involvement in technology transfer and commercialization can continue without jeopardizing academic work or the public's trust in them.
Renoprotection with Pituitary Adenylate Cyclase-Activating Polypeptide in Cyclosporine A-Induced Nephrotoxicity
Authors: Khan Altaf-M , Li Min , Brant Elizabeth , Maderdrut Jerome L. , Majid Dewan S.A. , Simon Eric E. , Batuman Vecihi
Published: May 2016

Background

Acute and long-term nephrotoxicity is the major dose-limiting factor for cyclosporine A (CsA). We evaluated the protective effects of pituitary adenylate cyclase-activating polypeptide (PACAP)38 on CsA-induced nephrotoxicity in human renal proximal tubule epithelial (human kidney-2) cells and in intact mice.

Methods

Confluent (human kidney-2 cells were exposed to CsA (25-50 μmol/L) in the presence or absence of PACAP38 or vasoactive intestinal peptide (10−10 to 10−6 M). For studies in vivo, male BALB/c mice (n = 5 in each group) were given a single intraperitoneal injection of CsA (5 mg/kg body weight). Treatment group received 20 μg of PACAP38 2 hours before exposure to CsA and additional doses daily for 10 days.

Results

Cyclosporine A caused oxidative injury, marked morphological alterations, apoptosis, and increased expression of transforming growth factor (TGF)-β1 in cell cultures. Pituitary adenylate cyclase-activating polypeptide 38 at 10−8 mol/L restored cell confluency, reduced TGF-β1 secretion, and preserved cell integrity. In mice, CsA caused tubular injury characterized by loss of tubular epithelial cell brush border membranes, tubular collapse, cellular necrosis, interstitial fibrosis, increased production of TGF-β1, and elevated serum creatinine (3.39 ± 0.21 vs 0.13 ± 0.02 mg/dL in controls, P < 0.01). Treatment with PACAP38 reduced TGF-β1 and tumor necrosis factor-α production in kidney, prevented epithelial-mesenchymal transition of the renal cells, and reduced serum creatinine levels to 1.01 ± 0.18 mg/dL, P < 0.01 versus CsA group.

Conclusions

Pituitary adenylate cyclase-activating polypeptide 38 ameliorated renal tubular injury, reduced oxidative injury, and inhibited the expression of TGF-β1 in CsA-exposed murine kidneys. Pituitary adenylate cyclase-activating polypeptide could be a novel renoprotective and antifibrotic agent for CsA nephrotoxicity.
Adiponectin Attenuates Hypoxia/Reoxygenation-Induced Cardiomyocyte Injury through Inhibition of Endoplasmic Reticulum Stress
Authors: Bian Yun-fei , Hao Xiao-yan , Gao Feng , Yang Hui-yu , Zang Nana , Xiao Chuan-shi
Published: May 2016

Adiponectin (APN) is a potent cardioprotective molecule. The present study aims to investigate the underlying mechanism(s) for its cardioprotective effect. We isolated primary cardiomyocytes from neonatal rats and established an in vitro model of hypoxia/reoxygenation (H/R). The cardiomyocytes were randomly divided into 6 groups: saline group (control), dithiothreitol group (5 mM dithiothreitol for 2 hours), H/R group, H/R + APN group (incubation with 30 μg/mL APN, followed by H/R), H/R + APN + SB203580 (SB) group (treatment with 30 μg/mL APN and 5 μM SB, followed by H/R), and H/R + SB group (exposure to 5 μM SB and then H/R). Cell death was detected by measuring lactate dehydrogenase release. The expression levels of hypoxia-inducible factor 1α and endoplasmic reticulum stress-related genes including GRP78, caspase-12, C/EBP homologous protein, and p38 mitogen-activated protein kinase were examined. Cardiomyocytes exposed to H/R showed a significant increase in lactate dehydrogenase leakage and hypoxia-inducible factor 1α protein levels compared with the control cells ( P < 0.05). The H/R-provoked cell death was profoundly attenuated by the pretreatment with APN alone, SB alone, or both, which was coupled with decreased expression of GRP78, caspase-12, C/EBP homologous protein, and p38 mitogen-activated protein kinase. These results provide new insights into the mechanism of APN-mediated cardioprotection, which may be partially due to inhibition of endoplasmic reticulum stress response.
Patent and License Pearls and Pitfalls for Taking an Idea to the Marketplace
Authors: Mukharji Indrani
Published: May 2016

Technology transfer is the process by which novel ideas at academic institutions emanating from research supported by public and private funds are transferred to the private sector for developing marketable products for public use and benefit. Because the primary mission of universities is education and research, technology transfer in an academic environment introduces many challenges. This field is new to most faculty members and is seldom a core mission of their academic careers. The process is also new and unfamiliar to most university administrators. However, universities are increasingly challenged to demonstrate how their research with public funds translates into public benefit. Technology transfer by universities has taken on a new dimension with a focus first on protecting the intellectual property emanating from academic research, then finding means to develop and commercialize such intellectual property for launching new products in the market for public use and benefit. The Bayh-Dole Act enacted in 1980 (Public Law 96-517) allowed universities to elect to retain title to inventions arising from their federally funded research and to grant licenses to the patents, copyrights, or trademarks deriving from these inventions. Universities are allowed to retain the royalties and to share them with the inventors. This article presents the perspectives of technology transfer professionals, specifically, what technology transfer offices do or can do to assist researchers with commercialization of the novel ideas in biomedical research. It also provides a list of successful therapeutics that stemmed from academic research. In conclusion, reference is made to some of the challenges of technology transfer.
Simvastatin Effects on Androgens, Inflammatory Mediators, and Endogenous Pituitary Gonadotropins among Patients with PCOS Undergoing IVF: Results from a Prospective, Randomized, Placebo-Controlled Clinical Trial
Authors: Rashidi Batool , Abediasl Jhila , Tehraninejad Ensiyeh , Rahmanpour Haleh , Sills Eric Scott
Published: May 2016

Objective

To evaluate effects of simvastatin on selected biochemical parameters and reproductive outcome among patients with polycystic ovary syndrome (PCOS) who undergo in vitro fertilization (IVF).

Methods

Patients with PCOS were randomized to receive either oral simvastatin, 20 mg/d (n = 32), or placebo (n = 32) in a prospective, double-blind, randomized clinical trial (NCT 005-75601) in parallel with controlled ovarian hyperstimulation for IVF. All patients were determined to be at average risk for cardiovascular disease, based on high-sensitivity C-reactive protein (hsCRP) measurement at entry. After an 8-week treatment interval concluding at periovulatory human chorionic gonadotropin administration, selected clinical and laboratory parameters were measured.

Results

Mean serum total testosterone level decreased by 25% in the simvastatin group, compared to a 10% reduction in the placebo group ( P < 0.001). A trend of lower serum luteinizing hormone levels was noted in experimental and control groups (29% vs 22%, respectively), although this difference was not significant ( P > 0.05). Neither fasting insulin nor quantitative insulin sensitivity check index were significantly impacted by simvastatin ( P > 0.05). As expected, total cholesterol was not modified among placebo patients but was significantly reduced after simvastatin ( P = 0.001). In addition, hsCRP and vascular cell adhesion protein-1 were both significantly lower after simvastatin therapy compared to controls ( P ≤ 0.005 for both). At study completion, no important change in body mass index was observed in either group ( P ≥ 0.60). Although oocyte maturation, fertilization, and clinical pregnancy rates were all higher after simvastatin, none of these improvements were statistically significant.

Conclusions

This report presents data from the first prospective, randomized, placebo-controlled clinical investigation of simvastatin in the setting of PCOS and IVF. Simvastatin seems to be compatible with gonadotropin therapy for IVF and can offer beneficial endocrine and cardiovascular effects for patients with PCOS who undergo embryo transfer. Although the observed improvements in reproductive function were mild, the reductions in hsCRP and vascular cell adhesion protein-1 after simvastatin treatment were significant, suggesting the need for further clinical trials to clarify simvastatin's impact on reproductive physiology.
Utility of Routine Hematological and Inflammation Parameters for the Diagnosis of Cancer in Involuntary Weight Loss
Authors: Baicus Cristian , Caraiola Simona , Rimbas Mihai , Patrascu Ruxandra , Baicus Anda ,   Grupul de Studiu al Scaderii Ponderale Involuntare, Baicus C. , Badea C. , Balanescu E. , Balea M. , Caraiola S. , Constantin G. , Constantinescu I. , Dimitriu L. , Georgescu D. , Ghizdavu O. , Haidar A. , Ghita M. , Iacob M. , Ionescu R.A. , Leru P. , Marian A. , Mateescu R.B. , Nanu A. , Nicolau A. , Nicolescu I. , Nitescu D. , Patrascu R. , Pompilian V. , Rimbas M. , Tanaseanu S. , Ticu G. , Ursica D. , Voiosu Th. , Voiosu R. , Baicus A.
Published: May 2016

Introduction

A quarter of patients with involuntary weight loss (IWL) have cancer. Inflammation and anemia are associated with cancer, and recent studies showed that red blood cell distribution width (RDW) is a predictor of mortality, including cancer-related death. The aim of this study was to assess the ability of routine hematological and inflammation parameters to diagnose cancer in patients with IWL.

Materials and Methods

A total of 253 consecutive patients with IWL admitted in a secondary care university hospital were included. Routine hematological and inflammatory parameters (hemoglobin level, mean corpuscular volume, RDW, serum iron level, erythrocyte sedimentation rate, C-reactive protein level, and ferritin level) were recorded for all patients. The investigative workup was not standardized, but the patients were followed up for 6 months to avoid misclassification concerning the final diagnosis.

Results

All parameters, excepting mean cellular volume, were statistically associated with cancer. The areas under the curve were 0.708 (95% confidence interval [CI], 0.627-0.790) for C-reactive protein level, 0.690 (95% CI: 0.620-0.760) for erythrocyte sedimentation rate, 0.651 (95% CI, 0.566-0.735) for serum iron level, 0.607 (95% CI, 0.526-0.687) for hemoglobin level, 0.598 (95% CI, 0.518-0.679) for ferritin level, 0.594 (95% CI, 0.517-0.671) for RDW, and 0.561 (95% CI, 0.474-0.649) for mean cellular volume. In the multivariable analysis, only erythrocyte sedimentation rate remained associated with cancer.

Conclusions

In patients with IWL, the hematological and inflammation parameters were statistically different in patients with cancer and in those without cancer. However, in clinical practice, they were modest diagnostic tests for cancer.
Relationship between Clinicopathologic Variables and Serum and Tissue Levels of Dickkopf-1 in Patients with Rectal Cancer
Authors: Kemik Ozgur , Kemik Ahu Sarbay , Sumer Aziz , Begenik Huseyin , Purisa Sevım , Tuzun Sefa , Kotan Cetın
Published: May 2016

The major biomarker for rectal cancer is the pathologic development of the tumor. In our study, we identified Dikkopf-1 (DKK1) as a novel biomarker and a therapeutic target for rectal cancer. To emphasize the biological and clinicopathologic significance, we performed tumor tissue and serum analysis of 150 rectal cancer samples with enzyme-linked immunosorbent assay. Serum DKK-1 levels are found significantly higher in controls, in poor differentiation, and depth of invasion (in pT3 and pT4), present lymph node metastasis, and TNM stage (in pT3 and pT4) according to good differentiation, depth of invasion (in pT1 and pT2), absent lymph node metastasis, and TNM stage (in pT1 and pT2; P < 0.001 and P < 0.0001, respectively). Tissue DKK-1 levels are found in patients with rectal cancer than in control tissues ( P < 0.0001). Dikkopf-1 correlated significantly with depth of invasion ( P = 0.009), lymph node metastasis ( P = 0.028), venous involvement ( P = 0.019), and advanced pTNM stage ( P = 0.001). There was no correlation between DKK-1 and age or sex ( P > 0.05). This marker is also a potential candidate for development of rectal cancer cells and cancer progression.
Effect of Infliximab Treatment on QT Intervals in Patients with Ankylosing Spondylitis
Authors: Senel Soner , Cobankara Veli , Taskoylu Ozgur , Guclu Aydin , Evrengul Harun , Kaya Mehmet Gungor
Published: May 2016

Background

Cardiovascular complications are one of the most common and the most serious extraskeletal manifestations of ankylosing spondylitis (AS). Infliximab, a monoclonal antibody against tumor necrosis factor, is widely used in the treatment of AS. QT dispersion (QTd), which relates to left ventricular function and is used as an index of cardiac dysrhythmia, may be useful as a prognostic guide. Early detection of possible cardiac involvement may not be clinically evident, whereas it may be detected by electrocardiography.

Objectives

The aim of this prospective study was to assess the effect of infliximab treatment on QT intervals in patients with AS.

Methods

Twenty-one patients (17 females and 4 males) with AS who were in the active phase of disease (Bath Ankylosing Spondylitis Disease Activity Index score >4) were enrolled in the study. Infliximab was administered intravenously at a dosage of 5 mg/kg at weeks 0, 2, and 6 and every 6 weeks thereafter. QT intervals were recorded before and after 6 months of treatment.

Results

QT corrected (QTc) for heart rate was significantly reduced in the patients with AS after 6 months of infliximab therapy (406 ± 5.5 vs 388 ± 6.6 milliseconds; P = 0.029). There was no difference in the QTc dispersion (34.3 ± 11.1 vs 34.1 ± 8.6; P = 0.171). Body mass index and lipid profile were slightly increased after the treatment, but the difference was statistically insignificant.

Conclusion

Inflammation can affect the ventricles with an unknown mechanism, and QTc may be slightly prolonged as a result in the active phase of AS. In our study, QTc was shortened under infliximab therapy by suppressing inflammation. Therefore, this effect may protect patients with AS from fatal arrhythmias and sudden cardiac death.
Statin Therapy Reduces Growth of Abdominal Aortic Aneurysms
Authors: Karrowni Wassef , Dughman Saadeddine , Hajj Georges P. , Miller Francis J.
Published: May 2016

Background

The aim of this study was to evaluate the influence of statins on the growth of small abdominal aortic aneurysms (AAAs).

Methods

We retrospectively examined AAA diameter in 211 patients who had undergone serial imaging surveillance.

Results

Patients treated with and without statins were similar regarding age, initial aneurysm size, diagnosis of diabetes and hypertension, and smoking history. Patients receiving statins had a decreased aneurysm growth rate compared with those patients not receiving statins (0.9 mm/y [interquartile range, −1.0 to +1.0] vs 3.2 mm/y [interquartile range, 2.0-4.9], P < 0.0001). This difference in the rate of growth was maintained after adjusting for potential confounding factors.

Conclusions

To date, this is the one of the largest retrospective studies demonstrating an association between statin use and decreased growth rate of AAA.
Evaluation of Oxidative Stress, the Activities of Paraoxonase and Arylesterase in Patients with Subclinical Hypothyroidism
Authors: Cebeci Egemen , Alibaz-Oner Fatma , Usta Murat , Yurdakul Selen , Erguney Mecdi
Published: May 2016

Introduction

In subclinical hypothyroidism (SH), serum lipid and lipoprotein concentrations are frequently changed. Compared with the healthy population, the levels of oxidized low-density lipoprotein cholesterol are higher, and the levels of high-density lipoprotein cholesterol are lower. In patients with SH, the mechanism of atherosclerosis may beattributed to the lipid abnormalities. There is evidence showing that oxidation plays an important role during the process of atherosclerosis. Inthis study, we evaluated the activity of paraoxonase (PON) and arylesterase (ARE) in patients with SH and investigated their relation with oxidative stress.

Methods

The study enrolled 25 patients with SH and 20 sex- and age-matched healthy controls. The patient group and the control group were compared in terms of the activity of PON and ARE and the oxidative stress index.

Results

Between 2 groups, no significant difference was found in terms of age, sex, serum levels of total cholesterol, low-density lipoprotein, and high-density lipoprotein. In the SH group, the activity of PON was significantly lower than that observed in the control group ( P < 0.05). Arylesterase activity also was significantly lower in the group with SH, compared with the control group ( P < 0.05). Oxidative stress index was found to be significantly higher in the patient group, compared with the healthy subjects ( P < 0.01). Oxidative stress index showed a strong positive correlation with the levels of thyroid stimulating hormone in all cases ( r = 0.60, P < 0.01).

Conclusions

The activity of PON and ARE were significantly decreased, and oxidative stress was increased in patients with SH. Lower activities of these 2 biomarkers indicate increased oxidative damage in SH. Atherosclerosis in SH can be attributed to increased oxidative stress.
CD200 Expression in B-Cell Chronic Lymphoproliferative Disorders
Authors: El Desoukey Nermeen Ahmed , Afify Reham Abd Aleem , Amin Dalia Gamil , Mohammed Rasha Faragaly
Published: May 2016

Background

Flow cytometry immunophenotyping (FCIP) is used for rapid, specific diagnosis of B-chronic lymphoproliferative disorders (BCLPDs). However, cases may deviate from the typical immunophenotype; therefore, there is a need for adding new marker(s) for differentiating BCLPDs. Lately, few researches highlighted CD200 expression in some BCLPDs. Our aim was to evaluate CD200 expression in different BCLPDs and whether adding CD200 to BCLPD-FCIP routine panels could improve the ability of their differential diagnosis.

Methods

We evaluated CD200 expression in 49 BCLPD patients and 26 age- and sex-matched control subjects. Flow cytometry immunophenotyping first panel included CD5, CD19, sIg, CD23, CD22, CD79b, and FMC7; for BCLPDs other than chronic lymphocytic leukemia (CLL) and mantle cell lymphoma, CD11c, CD103, CD25, and CD10 were evaluated.

Results

Using tricolor FCIP, CD200 showed high bright expression on CD5/19-positive clone in all B-CLL patients (100%), with a mean of 94% (SD, 11%); in the 2 cases of hairy cell leukemia, CD200 was brightly expressed on 96% and 99% of cells. In all other BCLPDs including mantle cell lymphoma, follicular lymphoma and splenic marginal zone lymphoma, CD200 expression (on CD19/22-positive cells) was less than 20% with a mean of 10% (SD, 8%) and a dim pattern. CD200 expression was significantly higher in CLL compared with non-Hodgkin lymphoma groups ( P < 0.001).

Conclusions

Evaluating CD200 expression has a great impact on accurate BCLPDs diagnosis and could be added to the BCLPD routine panels. The high expression of CD200 in B-cell CLL and hairy cell leukemia could open the option for targeted immune (anti-CD200) therapy.