bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased Expression of Vascular Endothelial Growth Factor is Associated with Hypertrophic Ligamentum Flavum in Lumbar Spinal Canal Stenosis
Authors: Jirathanathornnukul Napaphat , Limthongkul Worawat , Yingsakmongkol Wicharn , Singhatanadgige Weerasak , Parkpian Vinai , Honsawek Sittisak
Published: May 2016

Lumbar spinal canal stenosis (LSCS) is the most common spinal disorder in elderly patients, causing low back and leg pain, radiculopathy, and cauda equina syndrome. Vascular endothelial growth factor (VEGF) is a potent regulator of many cellular functions including proliferation, differentiation, wound healing, and angiogenesis. The present study aimed to investigate the pattern of VEGF expression in the ligamentum flavum (LF) of patients with LSCS. 24 patients with LSCS were recruited in this prospective study. We quantified and localized VEGF expression in LF tissues obtained during surgery. VEGF messenger RNA and protein expression in LF were determined using reverse transcription PCR (RT-PCR), and quantitative real-time PCR, immunohistochemistry, and ELISA. VEGF expression was significantly higher in the hypertrophic LF group than in the non-pathological LF group (p<0.01) as quantified by quantitative real-time PCR. Further ELISA analysis showed that the average concentration of VEGF in the hypertrophic LF was significantly elevated compared with that of controls (p<0.01). There was no correlation between the tissue VEGF expression of non-pathological LF and patient age in patients with LSCS. Moreover, the immunohistochemical study revealed that VEGF was positively stained on fibroblasts, inflammatory cells, and endothelial cells representing neovascularization within hypertrophic LF compared to the non-pathological LF of controls. The increased expression of VEGF was associated with the degenerative changes of hypertrophic LF, suggesting that VEGF could contribute to one of the mechanisms of pathogenesis in lumbar spinal stenosis.
Pancreatic Functions in Adolescents with Beta Thalassemia Major Could Predict Cardiac and Hepatic Iron Loading: Relation to T2-Star (T2*) Magnetic Resonance Imaging
Authors: Mokhtar Galila M , Ibrahim Wafaa E , Elbarbary Nancy S , Matter Randa M , Ibrahim Ahmed S , Sayed Safa M
Published: May 2016

The aim of this study is to assess the correlation between cardiac and hepatic T2* MRI findings with the endocrine and exocrine pancreatic functions in known patients with β-thalassaemia major (β-TM). A total of 50 adolescent patients with β-TM and 44 healthy controls were investigated via: serum amylase, lipase, triglyceride index, oral glucose tolerance test and T2* MRI, to assess iron content in the heart and liver. Diabetes was found in 20%, and 40% of patients had impaired fasting glucose (IFG). Cardiac T2* was less than 10 ms in 22% indicating heavy load with iron in cardiac tissues. There was a significant decrease in median serum amylase (63.5 vs 87.5 IU/L, p=0.003) and lipase (63 vs 90 IU/L, p=0.017) among patients in comparison with the control group. Patients with β-TM and diabetes had lower serum amylase (32 vs 68 IU/L), lipase (28 vs 79 IU/L), cardiac and hepatic T2* MRI (7 vs 25.5 ms; 3 vs 6 ms, p<0.001 for all) than those without diabetes. Similar results were found among patients with IFG when compared with others (p<0.001 for all). Cardiac and hepatic T2* were inversely correlated to triglyceride index (r=−0.376, p=0.014 and r=−0.475, p=0.001, respectively) and positively correlated to amylase (r=0.791 and r=0.790) and lipase (r=0.784 and r=0.783; p<0.001 for all). The endocrine and exocrine pancreatic functions might become an equivalent predictor to cardiac and hepatic iron overload, especially in countries where MRI is not available or where it is expensive. The early occurrence of these abnormalities warrants more intensive chelation therapy.
Cut-Off Values of Blood Mercury Concentration in Relation to Increased Body Mass Index and Waist Circumference in Koreans
Authors: Bae Suhyun , Park Soo-Jung , Yeum Kyung-Jin , Choi Beomhee , Kim Young-Sang , Joo Nam-Seok
Published: May 2016

Blood mercury (methyl-mercury) from environmental exposure may be related to inflammation in our body. We investigated the cut-off values of blood mercury concentration in relation to increased body mass index (BMI) and waist circumference. On the basis of data obtained from the Korea National Health and Nutrition Examination Survey (KNHANES, 2008–2012), 11,159 subjects (5543 males and 5616 females) were analyzed cross-sectionally. Partial correlation, linear regression, and analysis of covariance (according to the mercury quartile) tests were performed to evaluate the relationship between blood mercury and BMI or waist circumference. In addition, we determined the cut-off values of blood mercury concentration in relation to increased BMI and waist circumference in both genders. Mean values of blood mercury concentration were 5.07±0.07 μg/L in males and 3.59±0.04 μg/L in females. After log transformation of blood mercury, significant (p<0.001) correlation was found between blood mercury concentration and BMI or waist circumference. BMI and waist circumference showed a significant and gradual increase as mercury quartile increased in both genders. Blood mercury concentration was weakly but significantly (p<0.001) associated with BMI and waist circumference. Cut-off values of blood mercury concentration correlated with increased BMI and waist circumference were around 3.95 μg/L in males and 3.40 μg/L in females.
Prediction of Esophageal Varices and Variceal Hemorrhage in Patients with Acute Upper Gastrointestinal Bleeding
Authors: Rockey Don C , Elliott Alan , Lyles Thomas
Published: May 2016

In patients with upper gastrointestinal bleeding (UGIB), identifying those with esophageal variceal hemorrhage prior to endoscopy would be clinically useful. This retrospective study of a large cohort of patients with UGIB used logistic regression analyses to evaluate the platelet count, aspartate aminotransferase (AST) to platelet ratio index (APRI), AST to alanine aminotransferase (ALT) ratio (AAR) and Lok index (all non-invasive blood markers) as predictors of variceal bleeding in (1) all patients with UGIB and (2) patients with cirrhosis and UGIB. 2233 patients admitted for UGIB were identified; 1034 patients had cirrhosis (46%) and of these, 555 patients (54%) had acute UGIB due to esophageal varices. In all patients with UGIB, the platelet count (cut-off 122,000/mm3), APRI (cut-off 5.1), AAR (cut-off 2.8) and Lok index (cut-off 0.9) had area under the curve (AUC)s of 0.80 0.82, 0.64, and 0.80, respectively, for predicting the presence of varices prior to endoscopy. To predict varices as the culprit of bleeding, the platelet count (cut-off 69,000), APRI (cut-off 2.6), AAR (cut-off 2.5) and Lok Index (0.90) had AUCs of 0.76, 0.77, 0.57 and 0.73, respectively. Finally, in patients with cirrhosis and UGIB, logistic regression was unable to identify optimal cut-off values useful for predicting varices as the culprit bleeding lesion for any of the non-invasive markers studied. For all patients with UGIB, non-invasive markers appear to differentiate patients with varices from those without varices and to identify those with a variceal culprit lesion. However, these markers could not distinguish between a variceal culprit and other lesions in patients with cirrhosis.
Reduced Iron Parameters and Cognitive Processes in Children and Adolescents with Dm1 Compared to those with Standard Parameters
Authors: Mojs Ewa , Stanisławska–Kubiak Maia , Wójciak Rafał W , Wojciechowska Julita , Przewoźniak Sabina
Published: May 2016

Anemia in patients with diabetes is not scarce and may contribute to the complications of the disease. The risk of iron deficiency parameters in child sufferers of diabetes type 1, observed in studies, can lead to cognitive impairment. The aim of the study was to determine whether children and adolescents with diabetes type 1, in whom reduced ferric parameters are observed in control tests, may also show reduced cognitive performance. The study included 100 children with diabetes type 1 at the age of 6–17 years. During control tests, patients’ morphological blood parameters were measured: red blood cells (RBC), hemoglobin, glycosylated hemoglobin, hematocrit, RBC volume, the molar mass of hemoglobin in RBC (MCH), mean corpuscular hemoglobin in RBC and iron concentrations in serum using flame atomic absorption spectroscopy and the Wechsler Intelligence Scale for Children (WISC-R). Results in the group of children with a diabetes type 1 significantly lower concentration of three ferric parameters affect the non-verbal intelligence measured with WISC-R. The prevalence of reduced ferric parameters justifies further screening in all children with diabetes type 1 and taking up appropriate preventive measures to reduce the risk of their occurrence.
Influence of Obstructive Sleep Apnea on Ischemia-Modified Albumin Levels and Carotid Intima-Media Thickness
Authors: Karamanli Harun , Kiyici Aysel , Arik Bilal , Efe Duran , Akgedik Recep
Published: May 2016

Obstructive sleep apnea (OSA) is associated with an increased risk of atherosclerosis. Carotid intima-media thickness (CIMT) is strongly associated with the presence of significant risk factors for cardiovascular disturbances. A disturbance in the oxidative/antioxidative balance is involved in the pathogenesis of OSA and cardiovascular diseases. Ischemia-modified albumin (IMA) is suggested as a novel marker of oxidative stress; IMA can be defined as decreased binding of transitional metal ions to serum albumin in oxidative status. The purpose of this research was to evaluate the influence of OSA on IMA levels and CIMT. In total, 61 individuals with OSA with no comorbidities and 24 healthy controls with a similar body mass index and age were enrolled in this study. Serum levels of IMA, CIMT (estimated radiologically), and polysomnographic parameters, were determined and interpreted. Serum IMA levels were significantly higher in individuals with OSA compared with the control group (p=0.0003). CIMT was significantly higher in the OSA group compared with the control group (0.88± 0.26 mm vs 0.75±0.17 mm, p=0.005). The CIMT and serum IMA levels were positively correlated with the apnea-hypopnea index (r=0.35 and r=0.32, respectively), and with the oxygen desaturation index (r=0.34 and r=0.29, respectively) at baseline. Increased IMA levels and CIMT may be related to increased oxidative stress and risk of atherosclerosis in individuals with OSA.
Identification and Characterization of Human Dendritic Cell Subsets in the Steady State: A Review of Our Current Knowledge
Authors: Patel Vineet Indrajit , Metcalf Jordan Patrick
Published: May 2016

Dendritic cells (DC) are generally categorized as a group of rare antigen presenting cells that are to the crucial development of immune responses to pathogens and also of tolerance to self-antigens. Therefore, having the ability to identify DC in specific tissues and to test their functional abilities in the steady state are scientific gaps needing attention. Research on primary human DC is lacking due to their rarity and the difficulty of obtaining tissue samples. However, recent findings have shown that several different DC subsets exist, and that these subsets vary both by markers expressed and functions depending on their specific microenvironment. After discriminating from other cell types, DC can be split into myeloid and plasmacytoid fractions. While plasmacytoid DC express definite markers, CD123 and BDCA-2, myeloid DC encompass several different subsets with overlapping markers expressed. Such markers include the blood DC antigens BDCA-1 and BDCA-3, along with Langerin, CD1a and CD14. Marker specificity is further reduced when accounting for microenvironmental differences, as observed in the blood, primary lymphoid tissues, skin and lungs. The mixed leukocyte reaction (MLR) has been used to measure the strength of antigen presentation by specific DC subsets. Surface markers and MLR require standardization to enable consistent identification of and comparisons between DC subsets. To alleviate these issues, researchers have begun comparing DC subsets at the transcriptional level. This has allowed degrees of relatedness to be determined between DC in different microenvironments, and should be a continued area of focus in years to come.
Vitamin-D Status and Mineral Metabolism in Two Ethnic Populations with Sarcoidosis
Authors: Capolongo Giovanna , Xu Li Hao Richie , Accardo Mariasofia , Sanduzzi Alessandro , Stanziola Anna Agnese , Colao Annamaria , Agostini Carlo , Zacchia Miriam , Capasso Giovambattista , Adams-Huet Beverley , Moe Orson W , Maalouf Naim M , Sakhaee Khashayar , Hsia Connie C W
Published: May 2016

Vitamin-D insufficiency and sarcoidosis are more common and severe in African Americans (AA) than Caucasians. In sarcoidosis, substrate-dependent extrarenal 1,25-dihydroxyvitamin-D (1,25-(OH)2D) production is thought to contribute to hypercalciuria and hypercalcemia, and vitamin-D repletion is often avoided. However, the anti-inflammatory properties of vitamin-D may also be beneficial. We prospectively examined serum vitamin-D levels, calcium balance, and the effects of vitamin-D repletion in 86 AA and Caucasian patients with biopsy-proven active sarcoidosis from the USA (US) and Italy (IT) in university-affiliated outpatient clinics. Clinical features, pulmonary function, and calciotropic hormones were measured. 16 patients with vitamin-D deficiency and normal serum ionized calcium (Ca2+) were treated with oral ergocalciferol (50,000 IU/week) for 12 weeks. Baseline mineral parameters were similar in US (93% AA) and IT (95% Caucasian) patients irrespective of glucocorticoid treatment. Pulmonary dysfunction was less pronounced in IT patients. Nephrolithiasis (in 11% US, 17% IT patients) was associated with higher urinary calcium excretion. Vitamin-D deficiency was not more prevalent in patients compared to the respective general populations. As serum 25-hydroxyvitamin-D (25-OHD) rose postrepletion, serum 1,25-(OH)2D, γ-globulins, and the previously elevated angiotensin converting enzyme (ACE) levels declined. Asymptomatic reversible increases in Ca2+ or urinary calcium/creatinine (Ca/Cr) developed in three patients during repletion. In conclusion, Caucasian and AA patients show similar calcium and vitamin D profiles. The higher prevalence of hypercalciuria and nephrolithiasis in sarcoidosis is unrelated to endogenous vitamin-D levels. Vitamin-D repletion in sarcoidosis is generally safe, although calcium balance should be monitored. A hypothesis that 25-OHD repletion suppresses granulomatous immune activity is provided.
Mechanisms and Challenges in Translational Stroke Research
Authors: Lo Eng H , Ning MingMing
Published: May 2016

Translating basic science advances into clinical meaning has been challenging for stroke research. This does not, however, mean that the investigation of basic mechanisms is irrelevant. Translation is difficult because the underlying mechanisms are complex and ill-defined. The original focus on neuroprotection has now evolved into a broader consideration of the role of non-neuronal cells in stroke pathophysiology. The neurovascular unit may provide a conceptual framework within which interactions between neural, glial, and vascular cells comprise a basis for function and dysfunction in the central nervous system. Importantly, these cell–cell signaling pathways are also biphasic in nature, that is, mechanisms that are deleterious in the acute phase may surprisingly be required for neurovascular remodeling and plasticity during stroke recovery. Furthermore, injury-into-repair gradients are significantly influenced by a host of modifying factors and comorbidities. Rigorous dissection of these complex and recursive mechanisms should be required before they can be rationally targeted for stroke.
Genetics as a Molecular Window into Recovery, Its Treatment, and Stress Responses after Stroke
Authors: Juth Vanessa , Holman E Alison , Chan Michelle K , Cramer Steven C
Published: May 2016

Stroke remains a major source of adult disability in the USA and worldwide. Most patients show some recovery during the weeks to months following a stroke, but this is generally incomplete. An emerging branch of therapeutics targets the processes underlying this behavioral recovery from stroke toward the goal of reducing long-term disability. A key factor hampering these efforts is the very large degree of variability between stroke survivors. Available data suggest that genetic differences could explain an important fraction of the differences between subjects. The current review considers this from several angles, including genetic differences in relation to drugs that promote recovery. Genetic factors related to physiological and psychological stress responses may also be critically important to understanding recovery after stroke and its treatment. The studies reviewed provide insights into recovery and suggest directions for further research to improve clinical decision-making in this setting. Genetic differences between patients might be used to help clinical trials select specific patient subgroups, on a biological basis, in order to sharpen the precision with which new treatments are evaluated. Pharmacogenomic factors might also provide insights into inter-subject differences in treatment side effects for pharmacological prescriptions, and behavioral interventions, and others. These efforts must be conducted with the strictest ethical standards given the highly sensitive nature of genetic data. Understanding the effect of selected genetic measures could improve a clinician's ability to predict the risk and efficacy of a restorative therapy and to make maximally informed decisions, and in so doing, facilitate individual patient care.
New Insights into the Cellular and Molecular Mechanisms of Cold Storage Injury
Authors: Rauen Ursula , de Groot Herbert
Published: May 2016

Solid organ grafts, but also other biologic materials requiring storage for a few hours to a few days, are usually stored under hypothermic conditions. To decrease graft injury during cold storage, organ preservation solutions were developed many years ago. However, since then, modern biochemical and cell biologic methods have allowed further insights into the molecular and cellular mechanisms of cold storage injury, including further insights into alterations of the cellular ion homeostasis, the occurrence of a mitochondrial permeability transition, and the occurrence of free-radical-mediated hypothermic injury and cold-induced apoptosis. These new aspects of cold storage injury, which are not covered by preservation solutions in current clinical use and offer the potential for improvement of organ and tissue preservation, are presented here.
Immune Responses in Kidney Preservation and Reperfusion Injury
Authors: Kieran Niamh E. , Rabb Hamid
Published: May 2016

Organ preservation and reperfusion injury have significant detrimental effects on both short- and long-term organ function. Ischemia reperfusion injury (IRI) underlies organ transplant dysfunction, myocardial infarction, stroke, and shock. Multiple molecular pathways are engaged in reactive oxygen production, apoptosis, signaling, and tissue regeneration. There has been an increased understanding of the important role of immune and inflammatory pathways in IRI, both in humans and in experimental models. Both cellular and soluble components of the immune system are directly activated during IRI, and there is evidence that immune mediators directly contribute to organ dysfunction. Immune activation during IRI likely underlies the enhanced immunogenicity of ischemic organs, with resultant increased rejection and fibrosis. Novel human therapies targeting T and B cells for classic immune diseases can now be considered to prevent and treat IRI. Organ preservation injury and cold ischemia could well have distinct pathophysiology from warm IRI and represent an opportunity to develop improved preservation methods.
Preconditioning Strategies to Limit Graft Immunogenicity and Cold Ischemic Organ Injury
Authors: van der Woude Fokko J. , Schnuelle Peter , Yard Benito A.
Published: May 2016

During the transplant process, the graft is exposed to numerous events, which may enhance its immunogenicity. In particular, factors related to brain death, such as hemodynamic instability and systemic release of cytokines, cold preservation on harvesting, and reperfusion injury, are known to accumulate in harm, conveying a proinflammatory state to the graft before transplant. Alloimmune reactivity is initiated when the host immune system detects non-self-antigens in the context of “danger signals.” Eliminating these danger signals by modifying the graft before transplant has the potential to attenuate the alloimmune response. The molecules, which mediate danger signals, have not yet been fully identified. Free oxygen radicals and interferon-γ are important candidates. One of the most important protective mechanisms against oxidative stress is the heme oxygenase 1 system. Up-regulation of heme oxygenase 1 in grafts has been shown to prevent ischemia-reperfusion damage and improve long-term graft survival in various transplant models. The benefit of blocking the action of interferon-γ in kidney transplants is less clear because the compound plays such a complex and pivotal role in the immune response, and experimental data with interferon-γ receptor knockout mice are conflicting. It has recently become clear that catecholamines are important graft-modifying agents. Dopamine is capable of stimulating the induction of protective enzymes like heme oxygenase-1 (HO-1) rendering the organ more resistant to the insult of ischemia/reperfusion and inflammation. Retrospective clinical data suggest that treatment of brain-dead organ donors with catecholamines is associated with less rejection and a better long-term graft survival of kidneys transplanted from these donors. Catecholamines can also modulate cytokine production and prevent cold-induced damage. Other substances, such as proteoglycans and phosphatidylethanolamine-bound hyaluronic acid, may interfere with the actions of interferon-γ. Further studies of these compounds in experimental animal models and in prospective randomized clinical trials will help establish their efficacy in donor pretreatment. It is important to underscore that donor pretreatment will have great advantages for the recipient because an improved long-term graft survival could thus be achieved cost-efficiently and without great effort or side effects.
Effects of Type 2 Diabetes on the Regulation of Hepatic Glucose Metabolism
Authors: Basu Ananda , Shah Pankaj , Nielsen Michael , Basu Rita , Rizza Robert A.
Published: May 2016

Glucose production is inappropriately increased in people with type 2 diabetes both before and after food ingestion. Excessive postprandial glucose production occurs in the presence of decreased and delayed insulin secretion and lack of suppression of glucagon release. These abnormalities in hormone secretion, coupled with impaired insulin-induced suppression of glucose production and stimulation of splanchnic glucose uptake, likely account in large part for the excessive amounts of glucose that reach the systemic circulation for disposal by peripheral tissues following food ingestion. In contrast, when adequate basal insulin concentrations are present, neither glucagon-induced stimulation of glucose production nor glucose-induced suppression of glucose production differs in diabetic and nondiabetic subjects matched for gender, age, and degree of obesity. However, when insulin secretion is defective, lack of suppression of glucagon can cause substantial hyperglycemia by enhancing rates of glucose production. Therefore, normalization of hepatic glucose metabolism in people with type 2 diabetes mellitus likely will require normalization of insulin and glucagon secretion as well as hepatic insulin action.
Gluconeogenesis and Glycogenolysis in Health and Diabetes
Authors: Boden Guenther
Published: May 2016

Reviewed are data on gluconeogenesis (GNG) and glycogenolysis (GL) obtained in healthy volunteers and diabetic patients with newer, quantitative methods. Specifically addressed are effects of overnight and prolonged fasting, of acute changes in serum insulin and plasma free fatty acid (FFA) levels, as well as acute changes of combined FFA and insulin levels on GNG and GL in nondiabetic subjects and of abnormalities in GNG and GL in patients with type 1 and type 2 diabetes.
Mechanical thrombectomy for anterior circulation stroke: 5-year experience in a statewide service with differences in pretreatment time metrics across two hospitals sites
Authors: Kabra Ruchi , Phillips Timothy J , Saw Jacqui-Lyn , Phatouros Constantine C , Singh Tejinder P , Hankey Graeme J , Blacker David , Ghia Darshan , Prentice David , McAuliffe William
Published: May 2016

Objective

To audit our institutional mechanical thrombectomy (MT) outcomes for acute anterior circulation stroke and examine the influence of workflow time metrics on patient outcomes.

Methods

A database of 100 MT cases was maintained throughout May 2010—February 2015 as part of a statewide service provided across two tertiary hospitals (H1 and H2). Patient demographics, stroke and procedural details, blinded angiographic outcomes, and 90-day modified Rankin Scale (mRS) scores were recorded. The following time points in stroke treatment were recorded: stroke onset, hospital presentation, CT imaging, arteriotomy, and recanalization. Statistical analysis of outcomes, predictors of outcome, and differences between the hospitals was carried out.

Results

Thrombolysis in Cerebral Infarction (TICI) 2b/3 reperfusion was 79%. Forty-nine per cent of patients had good clinical outcomes (mRS 0–2). In a subgroup analysis of 76 patients with premorbid mRS 0–1 and first CT performed ≤4.5 h after stroke onset, 60% had good clinical outcomes. Patient and disease characteristics were matched between the two hospitals. H1 had shorter times between hospital presentation and CT (32 vs 55 min, p=0.01), CT and arteriotomy (33 vs 69 min, p=0.00), and stroke onset and recanalization (198 vs 260 min, p=0.00). These time metrics independently predicted good clinical outcome. Median days spent at home in the first 90 days was greater at H1 (61 vs 8, p=0.04) than at H2. A greater proportion of patients treated at H1 were independent (mRS 0–2) at 90 days (54% vs 42%); however, this was not statistically significant (p=0.22).

Conclusions

Outcomes similar to randomized controlled trials are attainable in ‘real-world’ settings. Workflow time metrics were independent predictors of clinical outcome, and differed between the two hospitals owing to site-specific organizational differences.
Prognostic value of TAPSE after therapy optimisation in patients with pulmonary arterial hypertension is independent of the haemodynamic effects of therapy
Authors: Ghio Stefano , Pica Silvia , Klersy Catherine , Guzzafame Eleonora , Scelsi Laura , Raineri Claudia , Turco Annalisa , Schirinzi Sandra , Visconti Luigi Oltrona
Published: May 2016

Objective

To evaluate the prognostic significance of right ventricular function assessed by echocardiography after start or escalation of targeted therapy in patients with pulmonary arterial hypertension.

Methods

Study design: longitudinal study. Setting: tertiary referral centre for pulmonary hypertension. Patients: 81 consecutive patients with pulmonary arterial hypertension (33 naive and 48 prevalent). Interventions: right heart catheterisation and echocardiography performed prior to starting or escalating targeted therapy and repeated in 55 patients after 4–12 months of therapy. Main outcome measure: survival after follow-up examinations.

Results

11 patients died and 7 were lost to follow-up during the first year; 8 patients underwent first follow-up evaluation beyond 1 year. 55 patients were re-evaluated after therapy; during the subsequent follow-up period of 25 months, 9 patients died, 7 worsened from WHO I/II to III/IV and 15 remained in WHO III/IV despite therapy. A baseline tricuspid annular plane systolic excursion (TAPSE) ≥15 mm was associated with a lower risk of death (HR=0.32; 95% CI 0.12 to 0.83, p=0.012). Attaining a TAPSE≥15 mm after therapy was associated with a significantly lower risk of death or clinical worsening (HR=0.2; 95% CI 0.1 to 0.6, p=0.002) and a lower risk of death which approached statistical significance (HR=0.3; 95% CI 0.2 to 1.1, p=0.075). Per cent changes in TAPSE were loosely related to changes in pulmonary vascular resistances after therapy (R=0.37).

Conclusions

In patients with pulmonary arterial hypertension, the evaluation of right ventricular function by TAPSE after targeted therapy is useful to predict subsequent prognosis, regardless of the haemodynamic effects of therapy.
Acquired Motility Disorders in Childhood
Authors: Milla PJ
Published: May 2016

Acquired motility
disorders in childhood cause a number of gastrointestinal symptoms
– principally, recurrent vomiting, abdominal pain and distension,
constipation and loose stools. Gastrointestinal motility
disorders result from disturbances of the control mechanisms of
gut motor activity, which may be produced by organic disease involving
enteric nerves and muscle, perturbation of the humoral
environment of the nerves and muscle, and altered central nervous
system input. In children, both congenital and acquired disease
processes may produce these pathogenetic mechanisms,
resulting in syndromes that vary in severity from chronic intestinal
pseudo‐obstruction to the irritable bowel syndrome.
Characterization of Pseudomonas aeruginosa Isolates Obtained from Patients in Canadian Hospitals: Results of the CANWARD 2007 Study
Authors: Walkty Andrew , DeCorby Melanie , Nichol Kim , McCracken Melissa , Mulvey Michael R , Karlowsky James A , Hoban Daryl J , Zhanel George G
Published: May 2016

INTRODUCTION: Pseudomonas aeruginosa is an important nosocomial
pathogen. The purpose of the present study was to evaluate the
antimicrobial susceptibility profile of P aeruginosa isolates obtained
from patients in different areas of Canadian hospitals.
METHODS: From January to December 2007 inclusive, 12 sentinel
hospitals across Canada submitted clinical isolates from patients
attending emergency rooms, medical wards, surgical wards and intensive
care units (ICUs) (the Canadian Ward Surveillance Study
[CANWARD 2007]). Each centre was asked to submit clinical isolates
(consecutive, one per patient per infection site) from blood (n=360),
respiratory (n=200), urine (n=100) and wound/intravenous (n=50)
infections. Susceptibility testing was performed using Clinical and
Laboratory Standards Institute broth microdilution methods.
Multidrug‐resistant (MDR; resistant to at least three different antimicrobial
classes) isolates were typed by pulsed‐field gel electrophoresis.
RESULTS: In total, 451 P aeruginosa isolates were collected (representing
7% of all CANWARD 2007 isolates). The rank order of antimicrobial
susceptibility was as follows (percent susceptible): amikacin
(93.1%) = piperacillin/tazobactam (93.1%) > meropenem (87.4%) >
cefepime (69.4%) > ciprofloxacin (67.2%) > gentamicin (66.1%) >
levofloxacin (60.5%). Reduced susceptibility to cefepime, meropenem
and levofloxacin was observed more frequently among ICU isolates
(P<0.05). Thirty‐four isolates (7.5%) were MDR. MDR isolates were
more likely to be obtained from patients in an ICU (P=0.003) and less
likely to come from a bloodstream source (P=0.008). Excluding colistin
(polymyxin E), amikacin and piperacillin/tazobactam, followed by
meropenem, were the most active antimicrobials evaluated versus the
MDR isolates. All of the MDR isolates were susceptible to colistin.
The majority of MDR isolates were genetically unrelated.
CONCLUSIONS: P aeruginosa is common among clinical specimens
from patients in Canadian hospitals. Of the antipseudomonal antimicrobials
evaluated, amikacin, meropenem and piperacillin/tazobactam
demonstrated the greatest in vitro activity. Isolates with reduced antimicrobial
susceptibility and MDR isolates were more often obtained
from ICU patients. All of the MDR isolates remained susceptible to
colistin.
Comparison of Community‐Associated and Health Care‐Associated Methicillin‐Resistant Staphylococcus aureus in Canada: Results from CANWARD 2007
Authors: Nichol Kimberly A , McCracken Melissa , DeCorby Melanie R , Thompson Kristjan , Mulvey Michael R , Karlowsky James A , Hoban Daryl J , Zhanel George G
Published: May 2016

BACKGROUND: Community‐associated methicillin‐resistant
Staphylococcus aureus (CA‐MRSA) differ from health care‐associated
MRSA (HA‐MRSA) in their genotypic and phenotypic characteristics.
The purpose of the present study was to compare the demographics,
antimicrobial susceptibilities and molecular epidemiology of
CA‐MRSA and HA‐MRSA in Canada.
METHODS: In 2007, 385 MRSA isolates were collected from
Canadian patients attending hospital clinics, emergency rooms, medical/
surgical wards and intensive care units. Susceptibilities to betalactams,
clarithromycin, clindamycin, daptomycin, levofloxacin,
linezolid, moxifloxacin, tigecycline, trimethoprim‐sulfamethoxazole
and vancomycin were determined by Clinical and Laboratory
Standards Institute broth microdilution. Strain typing was performed
by pulsed‐field gel electrophoresis (PFGE) and the mecA, nuc and pvl
genes were detected by polymerase chain reaction.
RESULTS: Of the 385 MRSA, 19.5% were CA‐MRSA and 79.2%
were HA‐MRSA as determined by PFGE. CA‐MRSA belonged to
PFGE types CMRSA10/USA300 (66.7%) and CMRSA7/USA400
(33.3%); PFGE types identified among HA‐MRSA included
CMRSA2/USA100/800 (81.6%), CMRSA6 (13.1%), CMRSA1/
USA600 (3.3%), CMRSA5/USA500 (1.3%), CMRSA3 (0.3%) and
CMRSA9 (0.3%). Panton‐Valentine leukocidin (PVL) was detected
in 94.7% of CA‐MRSA and 0.7% of HA‐MRSA. Resistance rates
(CA‐MRSA versus HA‐MRSA) were 61.3% versus 97.7% to levofloxacin,
73.3% versus 96.7% to clarithromycin, 12.0% versus 74.8% to
clindamycin and 0.0% versus 15.4% to trimethoprim‐sulfamethoxazole.
No MRSA were resistant to vancomycin, linezolid, tigecycline or
daptomycin.
CONCLUSIONS: CA‐MRSA represented 19.5% of all MRSA.
CA‐MRSA was significantly more susceptible to levofloxacin,
clarithromycin, clindamycin and trimethoprim‐sulfamethoxazole than
HA‐MRSA. Of CA‐MRSA, 94.7% were PVL‐positive while 99.3% of
HA‐MRSA were PVL‐negative. CA‐MRSA is an emerging pathogen
in Canadian hospitals.
Differentially Expressed miRNAs in Tumor, Adjacent, and Normal Tissues of Lung Adenocarcinoma
Authors: Tian Fei , Li Rui , Chen Zhenzhu , Shen Yanting , Lu Jiafeng , Xie Xueying , Ge Qinyu
Published: May 2016

Lung cancer is the leading cause of cancer deaths. Non-small-cell lung cancer (NSCLC) is the major type of lung cancer. The aim of this study was to characterize the expression profiles of miRNAs in adenocarcinoma (AC), one major subtype of NSCLC. In this study, the miRNAs were detected in normal, adjacent, and tumor tissues by next-generation sequencing. Then the expression levels of differential miRNAs were quantified by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). In the results, 259, 401, and 389 miRNAs were detected in tumor, adjacent, and normal tissues of pooled AC samples, respectively. In addition, for the first time we have found that miR-21-5p and miR-196a-5p were gradually upregulated from normal to adjacent to tumor tissues; miR-218-5p was gradually downregulated with 2-fold or greater change in AC tissues. These 3 miRNAs were validated by qRT-PCR. Lastly, we predicted target genes of these 3 miRNAs and enriched the potential functions and regulatory pathways. The aberrant miR-21-5p, miR-196a-5p, and miR-218-5p may become biomarkers for diagnosis and prognosis of lung adenocarcinoma. This research may be useful for lung adenocarcinoma diagnosis and the study of pathology in lung cancer.
Lovastatin Decreases the Expression of CD133 and Influences the Differentiation Potential of Human Embryonic Stem Cells
Authors: Kallas-Kivi Ade , Trei Annika , Maimets Toivo
Published: May 2016

The lipophilic statin lovastatin decreases cholesterol synthesis and is a safe and effective treatment for the prevention of cardiovascular diseases. Growing evidence points at antitumor potential of lovastatin. Therefore, understanding the molecular mechanism of lovastatin function in different cell types is critical to effective therapy design. In this study, we investigated the effects of lovastatin on the differentiation potential of human embryonic stem (hES) cells (H9 cell line). Multiparameter flow cytometric assay was used to detect changes in the expression of transcription factors characteristic of hES cells. We found that lovastatin treatment delayed NANOG downregulation during ectodermal and endodermal differentiation. Likewise, expression of ectodermal (SOX1 and OTX2) and endodermal (GATA4 and FOXA2) markers was higher in treated cells. Exposure of hES cells to lovastatin led to a minor decrease in the expression of SSEA‐3 and a significant reduction in CD133 expression. Treated cells also formed fewer embryoid bodies than control cells. By analyzing hES with and without CD133, we discovered that CD133 expression is required for proper formation of embryoid bodies. In conclusion, lovastatin reduced the heterogeneity of hES cells and impaired their differentiation potential.
Primary MALT Lymphoma of the Breast Treated with Definitive Radiation
Authors: Hissourou III Mohammad , Zia Sayyad Yaseen , Alqatari Mahfood , Strauchen James , Bakst Richard L.
Published: May 2016

We are reporting a case of a 59-year-old woman, with a family history of breast cancer, who presented with extranodal marginal zone lymphoma (MALT) of the left breast. She received definitive radiation therapy and remains without evidence of disease. Here, we present a case and review the current literature to determine the optimal treatment of this rare presentation of MALT.
Location Optimization for Square Array Antennas Using Differential Evolution Algorithm
Authors: Afacan Erkan
Published: May 2016

In recent works thinned arrays giving minimum peak sidelobe levels for planar square antenna arrays are obtained using Hadamard difference sets. In the current work thinned array configurations giving lower peak sidelobe levels than those given in the literature are obtained for square arrays of6×6,8×8,12×12, and16×16elements. Differential evolution algorithm is used in the determination of the antenna locations.
Fosfomycin: A First-Line Oral Therapy for Acute Uncomplicated Cystitis
Authors: Zhanel George G. , Walkty Andrew J. , Karlowsky James A.
Published: May 2016

Fosfomycin is a new agent to Canada approved for the treatment of acute uncomplicated cystitis (AUC) in adult women infected with susceptible isolates ofE. coliandEnterococcus faecalis. We reviewed the literature regarding the use of oral fosfomycin for the treatment of AUC. All English-language references from 1975 to October 2015 were reviewed. In Canada, fosfomycin tromethamine is manufactured as Monurol® and is available as a 3-gram single dose sachet. Fosfomycin has a unique chemical structure, inhibiting peptidoglycan synthesis at an earlier site compared toβ-lactams with no cross-resistance with other agents. Fosfomycin displays broad-spectrum activity against ESBL-producing, AmpC-producing, carbapenem-non-susceptible, and multidrug-resistant (MDR)E. coli. Resistance to fosfomycin inE. coliis rare (<1%). Fosfomycin is excreted unchanged in the urine by glomerular filtration with peak urinary concentration ~4000 µg/mL and remains at concentrations >100 µg/mL for 48 hours after a single 3-gram oral dose. No dosage adjustments are required in elderly patients, in pregnant patients, or in either renal or hepatic impairment. Fosfomycin demonstrates a favorable safety profile, and clinical trials have demonstrated efficacy in AUC that is comparable to ciprofloxacin, nitrofurantoin, and trimethoprim-sulfamethoxazole. Fosfomycin’s in vitro activity against common uropathogens, including MDR isolates, its favorable safety profile including pregnancy patients, drug interactions, and clinical trials data demonstrating efficacy in AUC, has resulted in Canadian, US, and European guidelines/authorities recommending fosfomycin as a first line agent for the treatment of AUC.
Weed Control in Corn (Zea maysL.) as Influenced by Preemergence Herbicides
Authors: Janak Travis W. , Grichar W. James
Published: May 2016

Field studies were conducted in central and south-central Texas from 2013 through 2015 to evaluate crop tolerance and efficacy of various preemergence herbicides alone and in combination for weed control in field corn. Acetochlor and pendimethalin alone,S-metolachlor plus mesotrione, and the three-way combination ofS-metolachlor plus atrazine plus mesotrione provided the most consistent control of annual grasses including browntop panicum (Panicum fasciculatumL.), Texas millet (Urochloa texanaL.), barnyardgrass (Echinochloa crus-galliL.), and sprawling signalgrass (Brachiaria reptansL.). Palmer amaranth [Amaranthus palmeri(S.) Wats.] control was at least 90% with fluthiacet-methyl plus pyroxasulfone, atrazine plus either acetochlor, alachlor, dimethenamid-P,S-metolachlor, orS-metolachlor plus mesotrione, saflufenacil plus dimethenamid-P, andS-metolachlor plus mesotrione. Hophornbeam copperleaf (Acalypha ostryifoliaL.) was difficult to control; however, acetochlor, saflufenacil or pyroxasulfone alone, saflufenacil plus dimethenamid-P, andS-metolachlor plus mesotrione provided at least 90% control. Acetochlor or saflufenacil alone, thiencarbazone-methyl plus isoxaflutole, dimethenamid-P plus atrazine, rimsulfuron plus mesotrione, and saflufenacil plus dimethenamid-P controlled common sunflower (Helianthus annuusL.) at least 90%. Corn injury was minimal (≤3%) with all herbicides. In general, corn grain yield was greatest with herbicide treatments containing more than one active ingredient compared with a single active ingredient.
Photon Conversion and Radiation Synergism in Eu/Tb Complexes Incorporated Poly Methyl Methacrylate
Authors: Xiao P. , Zhang J. J. , Wang Z. Q. , Lin H.
Published: May 2016

Green and red emissions in terbium and europium benzoic acids (TBA and EBA) incorporated poly methyl methacrylates (PMMA) are exhibited. Larger intensity parametersΩ2(11.13×10-20 cm2) andΩ4(13.15×10-20 cm2) ofEu3+indicate a high inversion asymmetrical and strong covalent environment around lanthanide (Ln) ions and maximum emission cross sectionσem-max(2.45×10-21 cm2) for the dominant transitionD50→F27ofEu3+reveals the effective photon conversion capacity in EBA incorporated PMMA. Color variation and fluorescence enhancement are validated to be originated from energy transfer and synergistic effect in TBA/EBA coincorporated PMMA system. The results indicate that Eu and Tb complexes incorporated PMMA with effective photon conversion hold great prospect in increment of lighting quality and enhancement of solar-cell efficiency employed in outer space.
Comparison of Plasma Neurosteroid and Prolactin Levels in Patients with Schizophrenia and Healthy Individuals
Authors: Riahi Forough , Izadi-mazidi Maryam , Ghaffari Ali , Yousefi Elham , Khademvatan Shahram
Published: May 2016

Background.The present study aimed to compare plasma levels of cortisol, testosterone, dehydroepiandrosterone (DHEA), and prolactin in patients with schizophrenia and healthy individuals.Method.A total of 100 patients with schizophrenia disorder (69 men and 31 women) and 190 healthy individuals (94 men and 96 women) participated in this cross-sectional study. They were tested for hormone levels and completed demographic questionnaires. Data were analyzed using multivariate analysis of variance (MANOVA) and one-way analysis of variance.Results.Serum testosterone level was significantly higher in men with schizophrenia than in healthy men. Women with schizophrenia had a significantly higher level of testosterone and lower level of prolactin compared to healthy women. There were no significant differences in hormone levels across various subtypes of schizophrenia. No significant differences also were observed in hormones levels in patients with first-episode schizophrenia disorder compared to those in patients with recurrent episodes.Conclusion.This study indicated that abnormal testosterone and prolactin levels might be associated with pathophysiology of schizophrenia disorder.
ROS, Cell Senescence, and Novel Molecular Mechanisms in Aging and Age‐Related Diseases
Authors: Davalli Pierpaola , Mitic Tijana , Caporali Andrea , Lauriola Angela , D’Arca Domenico
Published: May 2016

The aging process worsens the human body functions at multiple levels, thus causing its gradual decrease to resist stress, damage, and disease. Besides changes in gene expression and metabolic control, the aging rate has been associated with the production of high levels of Reactive Oxygen Species (ROS) and/or Reactive Nitrosative Species (RNS). Specific increases of ROS level have been demonstrated as potentially critical for induction and maintenance of cell senescence process. Causal connection between ROS, aging, age‐related pathologies, and cell senescence is studied intensely. Senescent cells have been proposed as a target for interventions to delay the aging and its related diseases or to improve the diseases treatment. Therapeutic interventions towards senescent cells might allow restoring the health and curing the diseases that share basal processes, rather than curing each disease in separate and symptomatic way. Here, we review observations on ROS ability of inducing cell senescence through novel mechanisms that underpin aging processes. Particular emphasis is addressed to the novel mechanisms of ROS involvement in epigenetic regulation of cell senescence and aging, with the aim to individuate specific pathways, which might promote healthy lifespan and improve aging.
Bifurcation Observation of Combining Spiral Gear Transmission Based on Parameter Domain Structure Analysis
Authors: Lin He , Wang Sanmin , Dowell Earl H. , Dong Jincheng
Published: May 2016

This study considers the bifurcation evolutions for a combining spiral gear transmission through parameter domain structure analysis. The system nonlinear vibration equations are created with piecewise backlash and general errors. Gill’s numerical integration algorithm is implemented in calculating the vibration equation sets. Based on cell-mapping method (CMM), two-dimensional dynamic domain planes have been developed and primarily focused on the parameters of backlash, transmission error, mesh frequency and damping ratio, and so forth. Solution demonstrates thatPeriod-doubling bifurcation happens as the mesh frequency increases; moreover nonlinear discontinuous jump breaks the periodic orbit and also turns the periodic state into chaos suddenly. In transmission error planes, three cell groups which arePeriod-1,Period-4, andChaoshave been observed, and the boundary cells are the sensitive areas to dynamic response. Considering the parameter planes which consist of damping ratio associated with backlash, transmission error, mesh stiffness, and external load, the solution domain structure reveals that the system step into chaos undergoesPeriod-doubling cascade withPeriod-2m(m: integer) periodic regions. Direct simulations to obtain the bifurcation diagram and largest Lyapunov exponent (LE) match satisfactorily with the parameter domain solutions.
Primary Diaphragmatic Dedifferentiated Liposarcoma in a Young Female Patient after Delivery
Authors: Sakata Shinya , Yoshida Chieko , Saeki Sho , Hirosako Susumu , Ichiyasu Hidenori , Kohrogi Hirotsugu
Published: May 2016

A 26-year-old woman was admitted with the chief complaint of chest pain. She had delivered her first child 9 months before admission. Computed tomography showed a bulky mass in her left chest, and histopathological analysis revealed it to be dedifferentiated liposarcoma. We initiated doxorubicin chemotherapy, and the tumor mass reduced. After that, we performed vascular embolization along with chemotherapy, but tumor size did not reduce. On the 160th day of illness, the patient died. This is the first report of a primary diaphragmatic dedifferentiated liposarcoma diagnosed after delivery. Establishment of a regimen of chemotherapy for bulky unresectable liposarcoma is necessary.