bluuebunny/crossref_metadata_2025 huggingface dataset:
A Phase 1 Study of the PARP Inhibitor Veliparib in Combination with Temozolomide in Acute Myeloid Leukemia
Authors: Gojo Ivana , Beumer Jan H. , Pratz Keith W. , McDevitt Michael A. , Baer Maria R. , Blackford Amanda L. , Smith B. Douglas , Gore Steven D. , Carraway Hetty E. , Showel Margaret M. , Levis Mark J. , Dezern Amy E. , Gladstone Douglas E. , Ji Jiuping Jay , Wang Lihua , Kinders Robert J. , Pouquet Marie , Ali-Walbi Ismail , Rudek Michelle A. , Poh Weijie , Herman James G. , Karnitz Larry M. , Kaufmann Scott H. , Chen Alice , Karp Judith E.
Published: August 2016

Purpose: In preclinical studies, the PARP inhibitor veliparib enhanced the antileukemic action of temozolomide through potentiation of DNA damage. Accordingly, we conducted a phase 1 study of temozolomide with escalating doses of veliparib in patients with relapsed, refractory acute myeloid leukemia (AML) or AML arising from aggressive myeloid malignancies.

Experimental Design: Patients received veliparib [20–200 mg once a day on day 1 and twice daily on days 4–12 in cycle 1 (days 1–8 in cycle ≥2)] and temozolomide [150–200 mg/m2 daily on days 3–9 in cycle 1 (days 1–5 in cycle ≥2)] every 28 to 56 days. Veliparib pharmacokinetics and pharmacodynamics [ability to inhibit poly(ADP-ribose) polymer (PAR) formation and induce H2AX phosphorylation] were assessed. Pretreatment levels of MGMT and PARP1 protein, methylation of the MGMT promoter, and integrity of the Fanconi anemia pathway were also examined.

Results: Forty-eight patients were treated at seven dose levels. Dose-limiting toxicities were oral mucositis and esophagitis lasting >7 days. The MTD was veliparib 150 mg twice daily with temozolomide 200 mg/m2 daily. The complete response (CR) rate was 17% (8/48 patients). Veliparib exposure as well as inhibition of PAR polymer formation increased dose proportionately. A veliparib-induced increase in H2AX phosphorylation in CD34+ cells was observed in responders. Three of 4 patients with MGMT promoter methylation achieved CR.

Conclusions: Veliparib plus temozolomide is well tolerated, with activity in advanced AML. Further evaluation of this regimen and of treatment-induced phosphorylation of H2AX and MGMT methylation as potential response predictors appears warranted. Clin Cancer Res; 23(3); 697–706. ©2016 AACR.
Cyclin-Dependent Kinase 14 Promotes Cell Proliferation, Migration and Invasion in Ovarian Cancer by Inhibiting Wnt Signaling Pathway
Authors: Ou-Yang Jun , Huang Li-Hong , Sun Xiang-Xiu
Published: August 2016

Objective: The study aimed to investigate cyclin-dependent kinase 14 (CDK14) and its co-function with Wnt signaling pathway on cell proliferation, migration and invasion in ovarian cancer. Methods: CDK14 expressions were detected by quantitative real-time polymerase chain reaction. The expressions c-Myc, cyclinD1, PFTK1, ki67 and OGT were examined by Western blot. MTT assay was applied to observe cell proliferation after transfection of pEGFP-N1/CDK14-siRNA and pEGFP-N1 into SKOV3 cells, and scratch test and Transwell assay to observe invasion and migration ability. Transfected tumor model in nude mice was established. Results: CDK14 was upregulated in the ovarian cancer tissues and cell lines (both p < 0.05). Expressions of downstream molecules in Wnt signaling pathway as well as the proliferation, invasion and migration ability of the SKOV3 cells were reduced when CDK14 was inhibited (all p < 0.05). The expression of β-catenin in the nucleus was also decreased when CDK14 was inhibited (p < 0.05). In the transfected tumor model of nude mice, the results showed, compared with the pEGFP-N1 group and blank control group, that the expressions of c-Myc, cyclinD1, PFTK1, ki67 and OGT in the pEGFP-N1/CDK14-siRNA group in the transplantation tumor tissues decreased significantly (all p < 0.05). Conclusion: CDK14 suppression-mediated Wnt signaling pathway can inhibit cell proliferation, invasion and migration in ovarian cancer.
Association of Intestinal Microbiota with Metabolic Markers and Dietary Habits in Patients with Type 2 Diabetes
Authors: Yamaguchi Yoshiharu , Adachi Kazunori , Sugiyama Tomoya , Shimozato Akihiro , Ebi Masahide , Ogasawara Naotaka , Funaki Yasushi , Goto Chiho , Sasaki Makoto , Kasugai Kunio
Published: August 2016

Background/Aims: Evidence suggests that intestinal microbiota, along with factors such as diet and host genetics, contributes to obesity, metabolic dysfunction and diabetes. Therefore, we examined the relationship between gut microbiota, blood metabolic markers, dietary habits and fecal short-chain fatty acids (SCFAs) in patients with type 2 diabetes mellitus (T2DM). Methods: Dietary habits, blood and fecal samples from 59 T2DM patients were recruited, and the association of intestinal microbiota with metabolic markers and dietary habits was analyzed. Results: Total energy intake was 1,692 ± 380 kcal/day. Carbohydrate, fat and protein intakes were 57.5 ± 5.2, 23.2 ± 5.3 and 13.2 ± 2.2%, respectively. Dietary habits - high carbohydrate, fat, and protein intake - were associated with increased counts of Clostridium clusters IV and XI and decreased counts of Bifidobacterium spp., order Lactobacillales and Clostridium cluster IV. Protein intake was negatively correlated with fecal acetate and total SCFAs. Total SCFAs, propionate and acetate were negatively correlated with blood insulin levels and the homeostasis model of insulin resistance. Conclusion: Diets low in protein and carbohydrates favor a healthy gut microbiome and improve glucose tolerance in T2DM patients, although further elucidation of the role of the gut microbiome could lead to better therapies and prophylaxes.
Symptomatic Primary Selective Immunoglobulin M Deficiency with Nonprotective Pneumococcal Titers Responsive to Subcutaneous Immunoglobulin Treatment
Authors: Patel Shiven S. , Fergeson Jennifer E. , Glaum Mark C. , Lockey Richard F.
Published: August 2016

Selective immunoglobulin M deficiency (SIgMD) is a rare disorder with varying clinical features. The prevalence of SIgMD is 0.03-3%. Patients may be asymptomatic or else present with recurrent infection, autoimmunity, atopic disease and/or malignancy. About 50% of patients with symptomatic SIgMD also have impaired antibody responses to the pneumococcal polysaccharide vaccine. We report on an adult who presented with symptomatic SIgMD with impaired pneumococcal polysaccharide antibody responses and lymphopenia, who experienced a significant clinical improvement in the frequency of infections after subcutaneous immunoglobulin replacement therapy.
Real-Life Study for the Diagnosis of House Dust Mite Allergy - The Value of Recombinant Allergen-Based IgE Serology
Authors: Becker Sven , Schlederer Thomas , Kramer Matthias F. , Haack Mareike , Vrtala Susanne , Resch Yvonne , Lupinek Christian , Valenta Rudolf , Gröger Moritz
Published: August 2016

Background:Dermatophagoides pteronyssinus is one of the most important perennial allergen sources worldwide. Molecular diagnostics using the commercially available major allergens (Der p 1 and Der p 2) in combination with Der p 10 do not detect house dust mite (HDM) sensitization in a number of cases when used alone. The objective was to evaluate the IgE reactivity profiles of these patients using an experimental immunoassay biochip. Methods: Sera of HDM-allergic patients (positive skin prick test, CAP class ≥1 for allergen extract, and positive intranasal provocation) were tested for IgE antibodies against Der p 1, Der p 2, and Der p 10 by ImmunoCAP fluorescence enzyme immunoassay. Negatively tested sera were examined by an experimental chip containing 13 microarrayed HDM allergens. Results: Of 97 patients tested, 16 showed negative results to Der p 1, Der p 2, and Der p 10. MeDALL chip evaluation revealed 5 patients monosensitized to Der p 23, and 11 patients were negative for all HDM MeDALL chip components. Seven sera were available for further testing, and 3 of them showed IgE reactivity to dot-blotted nDer p 1, and 2 reacted with high-molecular weight components (>100 kDa) in nitrocellulose-blotted HDM extract when tested with 125I-labeled anti-IgE in a RAST-based assay. The HDM extract-specific IgE levels of the 11 patients were <3.9 kU/l. Conclusions: Recombinant allergen-based IgE serology is of great value when conventional IgE diagnostics fails. Der p 23 is an important HDM allergen, especially when major allergens are negative. Therefore, it would be desirable to have Der p 23 commercially available. Further research concerning the prevalence and clinical significance of different HDM allergens is needed.
Oliguria and Biomarkers of Acute Kidney Injury: Star Struck Lovers or Strangers in the Night?
Authors: Lehner Georg F. , Forni Lui G. , Joannidis Michael
Published: August 2016

Oliguria is a common phenomenon that is found in hospitalized patients . Although a rapid reduction in urine excretion rate may reflect a precipitous fall in the glomerular filtration rate, in many cases it may not. Given the common physiological finding of oliguria, we explore the relationship between the functional biomarker of renal injury (oliguria) with the increasing number of markers of renal injury to see if this combination may aid in risk stratification.
Delayed Viral Clearance after 6-Week Treatment with Peginterferon Plus Ribavirin in a Patient with Chronic Hepatitis C Virus Genotype 1b
Authors: Sato Akira , Ishii Toshiya , Adachi Kayo , Takahashi Hideaki , Sano Fumiaki , Matsumoto Nobuyuki
Published: August 2016

Following interferon-based therapy for chronic hepatitis C, the negativity of hepatitis C virus RNA is essential to achieve viral clearance at the end of treatment. We report a case of clearance of chronic hepatitis C virus infection following early discontinuation (at 6 weeks) of peginterferon plus ribavirin therapy, without negativity for hepatitis C virus RNA during the treatment period. The patient was a 76-year-old Japanese male infected with hepatitis C virus genotype 1b and TT of IL28B rs8099917. Hepatitis C virus RNA remained positive at persistently low levels for more than 2 months after the cessation of therapy and became negative at 7 months after the discontinuation of therapy. Spontaneous clearance of hepatitis C virus RNA can occur following antiviral failure in patients with persistently low viral loads, and virological follow-up is therefore necessary in chronic hepatitis C virus infection, even after antiviral failure.
Accumulation of Advanced Glycation End Products Involved in Inflammation and Contributing to Severe Preeclampsia, in Maternal Blood, Umbilical Blood and Placental Tissues
Authors: Chen Weiping , Zhang Yan , Yue Chongyu , Ye Yuanhua , Chen Pingpin , Peng Wei , Wang Yufang
Published: August 2016

Objective: To investigate the expression of advanced glycation end products (AGEs) and the receptor for AGE (RAGEs) in maternal blood, umbilical blood and placental tissues in women with severe preeclampsia (sPE) as well as any association with inflammatory processes. Methods: The expressions of AGEs, RAGE, tumor necrosis factor-alpha (TNF)-α and vascular cell adhesion molecule-1 (VCAM)-1 in placental tissues were measured using immunohistochemistry. The levels of AGEs, RAGE, TNF-α and VCAM-1 in maternal blood, umbilical blood and placental extracts were assessed using enzyme-linked immunosorbent assays. Placental RAGE, TNF-α and VCAM-1 mRNA expression levels were determined by PCR. Placental AGEs, RAGE, TNF-α and VCAM-1 protein levels were determined by western blotting. Results: The levels of AGEs, TNF-α and VCAM-1 in the maternal tissues and umbilical blood were significantly higher in the sPE group than in the normal pregnancy (NP) controls (p < 0.05). The serum level of sRAGE in the umbilical blood was lower in the sPE group than in the NP controls (p < 0.05), while sRAGE was higher in the maternal blood of sPE than in the NP (p < 0.05). The maternal serum levels of AGEs were positively correlated with that of TNF-α and VCAM-1 in the maternal blood. There were no correlations between the levels of RAGE, TNF-α or VCAM-1 in maternal blood or umbilical serum. There were no correlations between the levels of sRAGE and TNF-α or VCAM-1 in maternal blood or umbilical serum. The levels of AGEs were positively correlated with those of TNF-α and VCAM-1 in placental lysates. Conclusion: AGEs and RAGE appear to act as important mediators in regulating the inflammatory pathways of preeclampsia.
The Promise of Mineralocorticoid Antagonism in Acute Kidney Injury
Authors: Chandrashekar Kiran B. , Lopez-Ruiz Arnaldo , Juncos Luis A.
Published: August 2016

Acute kidney injury (AKI) is a major cause of morbidity and mortality in hospitalized patients. Despite substantial progress being made in understanding the mechanisms contributing to the pathophysiology of AKI, we have so far been unsuccessful in devising adequate therapeutic strategies against the disease. A growing body of evidence suggests that the activation of mineralocorticoid receptors (MRs) may contribute to the exacerbation of AKI. Indeed, several studies have demonstrated the potential of MR antagonists in preventing and treating certain forms of experimental AKI. However, the main drawback of these medications is their side-effect profile. This has been addressed with the development of newer nonsteroidal MR antagonists, which have a comparable therapeutic profile without the side effects. This mini review aims at providing a brief overview of the rationale, potential benefits and challenges associated with the use of MR antagonists, particularly the novel nonsteroidal MR blockers, as therapy against AKI.
Ulcerated Giant Dermatofibroma following Routine Childhood Vaccination in a Young Boy
Authors: Ng Michelle S.Y. , Foong Alice Y.W. , Koh Mark J.A.
Published: August 2016

Introduction: The development of cutaneous neoplasms at immunization sites following vaccination is uncommon, and only few have been reported in the literature worldwide. We report an unusual case of an ulcerated giant dermatofibroma that developed as a chronic nonhealing plaque in the immunization scar of a young boy after vaccination. Case Report: A 13-month-old Chinese boy presented with an unusual skin reaction on the vaccination site at the right anterolateral thigh following a routine intramuscular injection of ‘5-in-1’ (diphtheria, tetanus, pertussis, polio and Haemophilus influenzae B) vaccine at 4 months of age. The immunization site developed a slightly raised papule with a central punctum that progressively grew in size, ulcerated and showed occasional bleeding over a span of 9 months. On follow-up, the lesion showed a chronic granulomatous reaction with surrounding induration and a central scarring. The right inguinal lymph node was palpable. Ultrasound of the lesion showed only nonspecific focal skin thickening. An incisional skin biopsy with careful histopathological evaluation revealed microscopic features consistent with an ulcerated giant dermatofibroma. Conclusion: Neoplastic development in immunization scars following vaccination is a rare occurrence and, hence, makes this case a diagnostic challenge. A high index of suspicion is crucial in atypical presentations of a common skin lesion, as typified by this case. Careful history taking and clinicopathological correlation of clinical findings with gross and microscopic findings along with targeted immunohistological staining is often essential to aid early diagnosis.
Team Reading (Peer Review) of Suspicious/Positive Slides for Continuous Quality Improvement in Cervical-Vaginal Cytology: A Comparison between Methods and Indicators
Authors: Placidi Antonio , Capparucci Paola , Di Luzio Antonella , Manca Gabriella , Mania Eloisa , Filippini Tommaso , Giorgi Rossi Paolo
Published: August 2016

Aim: In 2013, the Local Health Unit Roma 2 ex C screening laboratory introduced a new set of indicators for quality assurance. We compare 2 sets of indicators based on routine multiple readings (peer review) for their ability to identify problems in single-reader accuracy. Methods: All suspect slides were blindly reviewed by all the cytologists of the laboratory. The standard set of indicators includes interreader Cohen's kappa, positivity rate and atypical squamous cell of undetermined significance/squamous intraepithelial lesion (ASC-US/SIL) ratio. The new set included sensitivity for cervical intraepithelial neoplasia of grade 2 or worse (CIN2+), positive predictive value (PPV) and percentage of positive high-risk (HR)-HPV cases among ASC-US. In order to estimate sensitivity and PPV, we considered all women for whom there was a consensus of negative cytology, negative HR-HPV test, negative colposcopy or negative histology true negative. Results: Kappa values ranged from 0.521 to 0.753, with narrow 95% confidence intervals (CIs). Positivity rate ranged from 73.9 to 85.7 and the ASC-US/SIL ratio from 0.61 to 0.81. Sensitivity for CIN2+ at the low-grade SIL threshold ranged from 85.8 to 94.2, PPV ranged from 14.8 to 19.4, and both had a broad 95% CI. Readers with low sensitivity did not show low kappa values. The percentage proportion of HR-HPV-positives (HR-HPV+) among ASC-US ranged from 39.9 to 43.8% with a narrow 95% CI. Conclusion: The proportion of HR-HPV+ among ASC-US cases is a powerful indicator to address in training.
Epidemiology of Parkinson's Disease: A Population-Based Study in Primary Care in Italy
Authors: Pupillo Elisabetta , Cricelli Claudio , Mazzoleni Francesco , Cricelli Iacopo , Pasqua Alessandro , Pecchioli Serena , Lapi Francesco , Beghi Ettore
Published: August 2016

Background: There are no studies on prevalence, incidence and comorbidities of Parkinson's disease (PD) in the Italian population. Methods: The database of 700 Italian general practitioners (population, 923,356) was investigated. All patients with International Classification of Diseases Ninth Revision - Clinical Modification (ICD-9-CM) diagnosis of PD during the period 2002-2012 were included. Parkinsonisms were excluded. Clinical conditions preceding PD were identified through ICD-9-CM codes. The Charlson Comorbidity Index was used. PD crude and standardized prevalence and annual incidence were calculated. Crude and adjusted hazard ratios were calculated for comorbidities. Results: A total of 2,204 patients (1,140 men, 1,064 women, age 22-95 years) were included. The crude prevalence of PD was 239/100,000. Prevalence increased exponentially with age. Standardized prevalence was 233 (95% CI 232-235). One hundred ninety-four patients were newly diagnosed, giving a crude incidence of 22/100,000 and a standardized incidence of 23.1/100,000 (95% CI 22.9-23.2). Incidence increased steadily until age 75-84 years and then decreased. Older age, cardiovascular and gastrointestinal disorders, diabetes, and restless-legs syndrome were associated with increased PD risk and smoking and hypersomnia with decreased PD risk. The Charlson Comorbidity Index was associated with PD risk with a documented gradient. Conclusions: Prevalence and incidence of PD in Italy are in line with studies with the highest case ascertainment. PD risk varies with the number and type of comorbidities.
Comparisons of the Tono-Pen® and Goldmann Applanation Tonometer in the Measurement of Intraocular Pressure of Primary Open Angle Glaucoma Patients in a Hospital Population in Southwest Nigeria
Authors: Onochie Chizoba , Okoye Obiekwe , Ogunro Adunola , Aribaba Tade , Hassan Kunle , Onakoya Adeola
Published: August 2016

Objective: The aim of this study was to compare intraocular pressure (IOP) measured with the Tono-Pen® to that measured using the Goldmann applanation tonometer (GAT) in patients with primary open angle glaucoma attending a glaucoma clinic. Subjects and Methods: A comparative clinic-based observational study was conducted involving 75 patients (39 men and 36 women) attending a glaucoma clinic in Southwest Nigeria. A pretested structured questionnaire was used to collect sociodemographic data. The Tono-Pen and the GAT were used to measure the IOP in each patient. Central corneal thickness (CCT) was measured with an ultrasonic pachymeter, and the corrected GAT value was calculated for each patient. The Tono-Pen readings were compared with the uncorrected and corrected GAT readings. Descriptive and comparative analyses were performed. Values for p < 0.05 were considered statistically significant. Results: The mean age of the participants was 60.39 ± 16.71 years. The mean IOP using the Tono-Pen was 21.1 ± 6.8 mm Hg versus the mean uncorrected GAT value of 17.1 ± 6.9 mm Hg and the corrected GAT value of 18.9 ± 7.5 mm Hg. The mean CCT was 510.5 ± 29.6 µm. The mean differences between the Tono-Pen reading and uncorrected and corrected GAT readings were 3.9 ± 2.6 and 2.1 ± 3.5 mm Hg, respectively. Gender (Tono-Pen vs. GAT; p = 0.981 vs. 0.437) and corneal thickness (p = 0.057) did not significantly affect the IOP value. Of the 75 patients, 68 (90.7%) preferred the Tono-Pen to the GAT. Conclusion: In this study, the Tono-Pen gave a higher value for IOP than the uncorrected and corrected GAT values. Gender and corneal thickness did not significantly affect the measurements. Most patients found the Tono-Pen more acceptable than the GAT.
Postnatal Loss of Kindlin-2 Leads to Progressive Heart Failure
Authors: Zhang Zhiyuan , Mu Yongxin , Veevers Jennifer , Peter Angela K. , Manso Ana Maria , Bradford William H. , Dalton Nancy D. , Peterson Kirk L. , Knowlton Kirk U. , Ross Robert S. , Zhou Xinmin , Chen Ju
Published: August 2016

Background—

The striated muscle costamere, a multiprotein complex at the boundary between the sarcomere and the sarcolemma, plays an integral role in maintaining striated muscle structure and function. Multiple costamere-associated proteins, such as integrins and integrin-interacting proteins, have been identified and shown to play an increasingly important role in the pathogenesis of human cardiomyopathy. Kindlin-2 is an adaptor protein that binds to the integrin β cytoplasmic tail to promote integrin activation. Genetic deficiency of Kindlin-2 results in embryonic lethality, and knockdown of the Kindlin-2 homolog in
Caenorhabditis elegans
and
Danio rerio
suggests that it has an essential role in integrin function and normal muscle structure and function. The precise role of Kindlin-2 in the mammalian cardiac myocyte remains to be determined.

Methods and Results—

The current studies were designed to investigate the role of Kindlin-2 in the mammalian heart. We generated a series of cardiac myocyte–specific Kindlin-2 knockout mice with excision of the Kindlin-2 gene in either developing or adult cardiac myocytes. We found that mice lacking Kindlin-2 in the early developing heart are embryonic lethal. We demonstrate that deletion of Kindlin-2 at late gestation or in adult cardiac myocytes resulted in heart failure and premature death, which were associated with enlargement of the heart and extensive fibrosis. In addition, integrin β1D protein expression was significantly downregulated in the adult heart.

Conclusions—

Kindlin-2 is required to maintain integrin β1D protein stability. Postnatal loss of Kindlin-2 from cardiac myocytes leads to progressive heart failure, showing the importance of costameric proteins like Kindlin-2 for homeostasis of normal heart function.
Moderate Physical Activity in Healthy Adults Is Associated With Cardiac Remodeling
Authors: Dawes Timothy J.W. , Corden Ben , Cotter Sorcha , de Marvao Antonio , Walsh Roddy , Ware James S. , Cook Stuart A. , O’Regan Declan P.
Published: August 2016

Background—

Cardiac mass and volumes are often elevated in athletes, but it is not known whether moderate physical activity is also associated with cardiac dilatation and hypertrophy in a healthy adult population.

Methods and Results—

In total, 1096 adults (54% female, median age 39 years) without cardiovascular disease or cardiomyopathy-associated genetic variants underwent cardiac magnetic resonance imaging to determine biventricular volumes and function. Physical activity was assessed using a validated activity questionnaire. The relationship between cardiac parameters and activity was assessed using multiple linear regression adjusting for age, sex, race, and systolic blood pressure. Logistic regression was performed to determine the effect of activity on the likelihood of subjects having cardiac dilatation or hypertrophy according to standard cardiac magnetic resonance normal ranges. Increasing physical activity was associated with greater left ventricular (LV) mass (β=0.23;
P
<0.0001) and elevated LV and right ventricular volumes (LV: β=0.26,
P
<0.0001; right ventricular: β=0.26,
P
<0.0001). Physical activity had a larger effect on cardiac parameters than systolic blood pressure (0.06≤β≤0.21) and a similar effect to age (−0.20≤β≤−0.31). Increasing physical activity was a risk factor for meeting imaging criteria for LV hypertrophy (adjusted odds ratio 2.1;
P
<0.0001), LV dilatation (adjusted odds ratio 2.2;
P
<0.0001), and right ventricular dilatation (adjusted odds ratio 2.2;
P
<0.0001).

Conclusions—

Exercise-related cardiac remodeling is not confined to athletes, and there is a risk of overdiagnosing cardiac dilatation or hypertrophy in a proportion of active, healthy adults.
Noninvasive Contrast-Enhanced Ultrasound Molecular Imaging Detects Myocardial Inflammatory Response in Autoimmune Myocarditis
Authors: Steinl David C. , Xu Lifen , Khanicheh Elham , Ellertsdottir Elin , Ochoa-Espinosa Amanda , Mitterhuber Martina , Glatz Katharina , Kuster Gabriela M. , Kaufmann Beat A.
Published: August 2016

Background—

Cardiac tests for diagnosing myocarditis lack sensitivity or specificity. We hypothesized that contrast-enhanced ultrasound molecular imaging could detect myocardial inflammation and the recruitment of specific cellular subsets of the inflammatory response in murine myocarditis.

Methods and Results—

Microbubbles (MB) bearing antibodies targeting lymphocyte CD4 (MB
CD4
), endothelial P-selectin (MB
PSel
), or isotype control antibody (MB
Iso
) and MB with a negative electric charge for targeting of leukocytes (MB
Lc
) were prepared. Attachment of MB
CD4
was validated in vitro using murine spleen CD4+ T cells. Twenty-eight mice were studied after the induction of autoimmune myocarditis by immunization with α-myosin-peptide; 20 mice served as controls. Contrast-enhanced ultrasound molecular imaging of the heart was performed. Left ventricular function was assessed by conventional and deformation echocardiography, and myocarditis severity graded on histology. Animals were grouped into no myocarditis, moderate myocarditis, and severe myocarditis. In vitro, attachment of MB
CD4
to CD4+ T cells was significantly greater than of MB
Iso
. Of the left ventricular ejection fraction or strain and strain rate readouts, only longitudinal strain was significantly different from control animals in severe myocarditis. In contrast, contrast-enhanced ultrasound molecular imaging showed increased signals for all targeted MB versus MB
Iso
both in moderate and severe myocarditis, and MB
CD4
signal correlated with CD4+ T-lymphocyte infiltration in the myocardium.

Conclusions—

Contrast-enhanced ultrasound molecular imaging can detect endothelial inflammation and leukocyte infiltration in myocarditis in the absence of a detectable decline in left ventricular performance by functional imaging. In particular, imaging of CD4+ T cells involved in autoimmune responses could be helpful in diagnosing myocarditis.
Orthostatic Hypotension in the ACCORD (Action to Control Cardiovascular Risk in Diabetes) Blood Pressure Trial
Authors: Fleg Jerome L. , Evans Gregory W. , Margolis Karen L. , Barzilay Joshua , Basile Jan N. , Bigger J. Thomas , Cutler Jeffrey A. , Grimm Richard , Pedley Carolyn , Peterson Kevin , Pop-Busui Rodica , Sperl-Hillen JoAnn , Cushman William C.
Published: August 2016

Orthostatic hypotension (OH) is associated with hypertension and diabetes mellitus. However, in populations with both hypertension and diabetes mellitus, its prevalence, the effect of intensive versus standard systolic blood pressure (BP) targets on incident OH, and its prognostic significance are unclear. In 4266 participants in the ACCORD (Action to Control Cardiovascular Risk in Diabetes) BP trial, seated BP was measured 3×, followed by readings every minute for 3 minutes after standing. Orthostatic BP change, calculated as the minimum standing minus the mean seated systolic BP and diastolic BP, was assessed at baseline, 12 months, and 48 months. The relationship between OH and clinical outcomes (total and cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, heart failure hospitalization or death and the primary composite outcome of nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death) was assessed using proportional hazards analysis. Consensus OH, defined by orthostatic decline in systolic BP ≥20 mm Hg or diastolic BP ≥10 mm Hg, occurred at ≥1 time point in 20% of participants. Neither age nor systolic BP treatment target (intensive, <120 mm Hg versus standard, <140 mm Hg) was related to OH incidence. Over a median follow-up of 46.9 months, OH was associated with increased risk of total death (hazard ratio, 1.61; 95% confidence interval, 1.11–2.36) and heart failure death/hospitalization (hazard ratio, 1.85, 95% confidence interval, 1.17–2.93), but not with the primary outcome or other prespecified outcomes. In patients with type 2 diabetes mellitus and hypertension, OH was common, not associated with intensive versus standard BP treatment goals, and predicted increased mortality and heart failure events.
Surgical Valvotomy Versus Balloon Valvuloplasty for Congenital Aortic Valve Stenosis: A Systematic Review and Meta‐Analysis
Authors: Hill Garick D. , Ginde Salil , Rios Rodrigo , Frommelt Peter C. , Hill Kevin D.
Published: August 2016

Background

Optimal initial treatment for congenital aortic valve stenosis in children remains unclear between balloon aortic valvuloplasty (
BAV
) and surgical aortic valvotomy (
SAV
).

Methods and Results

We performed a contemporary systematic review and meta‐analysis to compare survival in children with congenital aortic valve stenosis. Secondary outcomes included frequency of at least moderate regurgitation at hospital discharge as well as rates of aortic valve replacement and reintervention. Single‐ and dual‐arm studies were identified by a search of PubMed (Medline), Embase, and the Cochrane database. Overall 2368 patients from 20 studies were included in the analysis, including 1835 (77%) in the
BAV
group and 533 (23%) in the
SAV
group. There was no difference between
SAV
and
BAV
in hospital mortality (
OR
=0.98, 95%
CI
0.5–2.0,
P
=0.27, I
2
=22%) or frequency of at least moderate aortic regurgitation at discharge (
OR
=0.58, 95%
CI
0.3–1.3,
P
=0.09, I
2
=54%). Kaplan–Meier analysis showed no difference in long‐term survival or freedom from aortic valve replacement but significantly more reintervention in the
BAV
group (10‐year freedom from reintervention of 46% [95%
CI
40–52] for
BAV
versus 73% [95%
CI
68–77] for
SAV
,
P
<0.001). Results were unchanged in a sensitivity analysis restricted to infants (<1 year of age).

Conclusions

Although higher rates of reintervention suggest improved outcomes with
SAV
, indications for reintervention may vary depending on initial intervention. When considering the benefits of a less‐invasive approach, and clinical equipoise with respect to more clinically relevant outcomes, these findings support the need for a randomized controlled trial.
Neotropical osmylids (Neuroptera, Osmylidae): Three new species of Isostenosmylus Krüger, 1913, new distributional records, redescriptions, checklist and key for the Neotropical species
Authors: MARTINS CALEB CALIFRE , ARDILA-CAMACHO ADRIAN , ASPÖCK ULRIKE
Published: August 2016

Osmylidae is a small family of Neuroptera with a worldwide distribution. Only four subfamilies and five genera of Osmylidae have been reported to date for the Neotropical region, with a total of 16 species, whilst 200 species are known in the world. In this study three new species are described—Isostenosmylus bifurcatus n. sp., I. irroratus n. sp. and I. julianae n. sp. Moreover, species of Gumilla Navás, 1912 and Paryphosmylus Krüger, 1913 are redescribed; additionally one larva of Isostenosmylus sp. and the female of Isostenosmylus fasciatus Kimmins, 1940 are described. Images of type specimens of Neotropical species of Osmylidae are provided. New records of known species are reported and a distribution map is presented. An updated checklist and a key for Neotropical species of Osmylidae are provided.
Identifying the Self-Anticipated Reoffending Risk Factors of Incarcerated Male Repeat Offenders in Hong Kong
Authors: Chan Heng Choon (Oliver) , Lo T. Wing , Zhong Lena Y.
Published: August 2016

Recidivism research on Hong Kong’s incarcerated population is limited, and little is known about the reoffending risk of incarcerated repeat offenders. The purpose of this study is to identify the reoffending risk of a sample of incarcerated male offenders with previous incarceration record based on their anticipation of reoffending. Using a self-reported methodological design, 351 incarcerated violent and nonviolent offenders are sampled. A number of self-anticipated reoffending risk factors are identified. The offenders’ age, illicit drug use, pro-offending attitudes, negative self-perception, familial detachment, deviant peer influence, poor prosocial attachment, and domestic and community criminogenic exposures are found to have significant predictive effects on their self-anticipated reoffending risk. Implications for intervention strategies with emphasis on these risk factors are discussed.
Males Perform Better in Identifying Voices During Menstruation Than Females
Authors: Wang Xue , Xu Xin , Liu Yangyang
Published: August 2016

The objective of the present study is to investigate gender differences in the ability to identify females’ voice during menstruation. In Study 1, 55 male participants ( M age = 19.6 years, SD = 1.0) were asked to listen to vocal samples from women during both ovulation and menstruation and to identify which recordings featured menstruating women. The results showed that the accuracy of men’s responses ( M = 56.73%, SD = 0.21) was significantly higher than 50%. In Study 2, 118 female students ( M age = 19.4 years, SD = 1.6) completed the same task. The results indicated that the accuracy of women’s performance was nearly 50%. These preliminary findings suggest that men are better able to identify women’s voices during menstruation than women. Future work could consider several significant variables for the purpose of validating the results.
Impact of the DSM-V Attention Deficit Hyperactivity Disorder Criteria for Diagnosing Children With High IQ
Authors: Thongseiratch Therdpong , Worachotekamjorn Juthamas
Published: August 2016

This study compared the number of attention deficit hyperactivity disorder (ADHD) cases defined by Diagnostic and Statistical Manual (DSM)-IV versus DSM-V criterion in children who have learning or behavioral problems with high IQ. The medical records of children ≤15 years of age who presented with learning or behavioral problems and underwent a Wechsler Intelligence Scale for Children (WISC)-III IQ test at the Pediatric Outpatient Clinic unit between 2010 and 2015 were reviewed. Information on DSM-IV and DSM-V criteria for ADHD were derived from computer-based medical records. Twenty-eight children who had learning or behavioral problems were identified to have a full-scale IQ ≥120. Sixteen of these high-IQ children met the DSM-IV criteria diagnosis for ADHD. Applying the extension of the age-of-onset criterion from 7 to 12 years in DSM-V led to an increase of three cases, all of which were the inattentive type ADHD. Including the pervasive developmental disorder criterion led to an increase of one case. The total number of ADHD cases also increased from 16 to 20 in this group. The data supported the hypothesis that applying the extension of the age-of-onset ADHD criterion and enabling the diagnosis of children with pervasive developmental disorders will increase the number of ADHD diagnoses among children with high IQ.
An Integrative Review of the Quality and Outcomes of Diabetes Education Programs for Children and Adolescents
Authors: Colson Sébastien , Côté José , Gentile Stéphanie , Hamel Valérie , Sapuppo Cédric , Ramirez-Garcia Pilar , Reynaud Rachel , Lagouanelle-Simeoni Marie-Claude
Published: August 2016

Purpose

The purpose of this study was twofold: (1) to describe the content of recent diabetes education programs and their outcomes in terms of glycemic control, disease management, and psychosocial criteria for children and adolescents with type 1 diabetes and (2) to gauge the match between these programs and the recommendations of the International Society for Pediatric and Adolescent Diabetes (ISPAD).

Methods

The integrative review was carried out according to the Cochrane recommendations. Thirteen databases were searched for evaluations of education programs published from 2009 to 2014. Program characteristics and outcomes were described. Quality of studies was assessed, and program match with ISPAD recommendations was gauged.

Results

Of 2528 studies found, 43 covering 36 education programs intended for youth with type 1 diabetes were retained for review. Nine of these centered on self-care competencies, 18 on psychosocial competencies, and 9 on both types of competency (mixed program). Programs varied widely in terms of organization, procedure, and content. Glycemic control was an indicator assessed in the majority of programs, but only half of these (for the most part, self-care programs) reported positive findings in this regard. Few programs seemed to affect psychosocial indicators. An online mixed program, which was the program that best met the ISPAD recommendations, proved to have an influence on glycemic control and several psychosocial criteria.

Conclusions

Various avenues can be considered to improve participant engagement in education programs and to align these programs more closely with international recommendations. Further research is required to enhance knowledge in this field.
Desperate Housewives? Differences in Work Satisfaction Between Stay-At-Home and Employed Mothers, 1972-2012
Authors: Cranney Stephen , Miles Andrew
Published: August 2016

Stay-at-home and employed mothers have been the subject of a wide range of both academic and popular discourse about roles, satisfaction, and meaning. However, no literature has examined time trends in relative satisfaction with being a stay-at-home versus a working mother. Here, we use pooled, yearly data from the General Social Survey to examine trends in how satisfied stay-at-home mothers are with their work relative to employed mothers. We find that stay-at-home mothers used to report less satisfaction with their work than employed mothers, but this gap became statistically nonsignificant around the same time trends in which societal attitudes toward gender roles began to shift. These changes are widespread across different socioeconomic and ideological groups, and do not appear to be attributable to sociodemographic composition changes.
Student Identity and Aversions to Science
Authors: Brooks Catherine F.
Published: August 2016

Biodiversity informatics (BDI) is a science focused on biodiversity data management, and BDI courses cast students’ attention to matters related to the physical environment, global change, translating data collections across multiple sciences, and also to the translation needed to bring BDI findings from the scholarly community to the public. Even as students learn about science communication in BDI courses, they struggle to translate their studies into their own identities and lives. Based on an examination of student talk in a course on BDI and Science Communication, this research illustrates how students linguistically frame science and their science identity. The data show that obstacles barring the taking up of a science identity are plentiful, and that those barriers often relate to issues of identity and language. Interventions for addressing this translational problem, the disruptions to sharing scientific information, are discussed.
Preclinical anaylses of [18F]cEFQ as a PET tracer for imaging metabotropic glutamate receptor type 1 (mGluR1)
Authors: Lee Boeun , Kim Yu Kyeong , Lee Ji Youn , Kim Young Joo , Lee Yun-Sang , Lee Dong Soo , Chung June-Key , Jeong Jae Min
Published: August 2016

Metabotropic glutamate receptor type 1 (mGluR1) is related with various neurological and psychiatric diseases, such as anxiety, depression, epilepsy, Parkinson’s disease, and neuropathic pain. Hence, mGluR1 is an important target for drug development and imaging. We synthesized [18F]cEFQ (3-ethyl-2-[18F]fluoroquinolin-6-yl cis-(4-methoxycyclohexyl)methanone) as a PET tracer for selective mGluR1 imaging and evaluated its properties in rodents. A chloroquinoline precursor was labeled by a nucleophilic substitution reaction, and the resulting [18F]cEFQ was obtained with high radiochemical purity (>99%) and specific activity (63-246 GBq/µmol). The log D value was 3.24, and the initial brain uptake at 10 min was over 4% of injected dose per gram in BALB/c mice. According to PET/CT and autoradiography in SD rats, [18F]cEFQ showed wide distribution in the whole brain and the highest uptake in the cerebellum. Pre-treatment with unlabeled cEFQ or the mGluR1-specific antagonist JNJ16259685 blocked the uptake of [18F]cEFQ. However, the uptake was not blocked by pre-treatment with the mGluR5-specific antagonist ABP688. The trans isomer [18F]tEFQ did not show high uptake in the mGluR1-rich region. [18F]cEFQ was straightforwardly prepared using a chloro-derivative precursor. Its feasibility as a specific and selective PET agent for imaging mGluR1 was proved by in vitro and in vivo experiments using rodents.
Pro-atherogenic mediators and subclinical atherogenesis are related to epicardial adipose tissue thickness in patients with cardiovascular risk
Authors: Peraza-Zaldívar Juan A , Suárez-Cuenca Juan A , Aceves-Millán Rocío , Ixcamparij-Rosales Carlos , Amezcua Lilia , Pérez-Cabeza de Vaca Rebeca , Guerrero-Celis Nuria , Melchor-López Alberto , Mondragón-Terán Paul , Alcaráz-Estrada Sofía L
Published: August 2016

Objective

To evaluate the relationship between pro-atherogenic biomarkers and epicardial adipose tissue (EAT) thickness in patients with cardiovascular risk factors.

Methods

Plasma nitric oxide (NO), soluble intercellular adhesion molecule-1 and malondialdehyde (MDA) levels, EAT thickness, flow-mediated dilation (FMD) and carotid intima media thickness (CIMT) were determined in patients aged >18 years who were referred for echocardiography for heart ischemia or non-ischemic diseases. Cardiovascular risk factors (Framingham score [FS] ≥ 20) were weighted.

Results

Hypertension, dyslipidaemia and type 2 diabetes mellitus were prevalent (≥55% of 40 patients). Patients with FS ≥ 20 ( n = 21) showed significantly higher EAT and CIMT values. Globally, MDA, CIMT, age, waist circumference, high-density lipoprotein cholesterol (HDL-C) and FS were associated with EAT thickness. EAT was significantly associated with NO in patients with FS ≥ 20. Significant differences in EAT thickness were found between patients stratified by NO value, FMD, age, smoking status, dyslipidaemia, type 2 diabetes mellitus and FS. An EAT-associated atherogenic risk (CIMT ≥ 1 mm) model was statistically significant when MDA and type 2 diabetes mellitus were included.

Conclusion

EAT thickness was associated with MDA, CIMT, age, waist circumference, HDL-C and FS globally, but with NO only in patients with FS≥20. EAT may be used to identify vascular damage stage, possibly influenced by MDA and type 2 diabetes mellitus.
Predictors of Intimate Partner Homicide in a Sample of Portuguese Male Domestic Offenders
Authors: Cunha Olga Soares , Gonçalves Rui Abrunhosa
Published: August 2016

Intimate partner homicide (IPH) is a major social problem, and it is important to determine the predictors of this violent behavior. The purpose of this study was to examine the differences between intimate partner violence (IPV) and IPH and to identify the variables that predict IPH. The sample was composed of 35 perpetrators of IPH, who were compared with 137 perpetrators of IPV. The data were collected using the Spousal Abuse Risk Assessment. The data suggest that IPH presents different dynamics from IPV. Being older, exhibiting suicidal and/or homicidal ideation/intent, and the use of weapons and/or credible threats of death substantially increase a man’s risk of committing IPH. Inversely, not being single, violating conditional release, and being victimized in childhood decrease the likelihood of committing IPH. These findings reinforce the assumption that IPV and IPH have both commonalities and differences and challenge the view that IPV and IPH are different phenomena and that intimate partner murder is an inexplicable event. Implications for preventing IPV and IPH are discussed.
‘Vulnerable’ girls, education and non-governmental organisation sponsorship programmes in Kampala
Authors: Óskarsdóttir Selma Sif Ísfeld , Baldursdóttir Sigríður , Einarsdóttir Jónína
Published: August 2016

Many non-governmental organisations exclusively sponsor education of ‘vulnerable’ girls who are seen as poor, oppressed and sexually abused. Based on fieldwork conducted in Kampala, Uganda, in 2012, we explore the views of sponsored girls, non-governmental organisation staff and educators on ‘vulnerability’ and scholarship programmes. Educators and non-governmental organisation staff agreed the sponsored girls were at risk of having relationships with ‘sugar daddies’ and becoming pregnant. Although the girls acknowledged their lives had been tough, they did not see themselves as ‘vulnerable’. While western representations of Third World women identified by Mohanty mostly apply for ‘vulnerable’ girls, the sponsorship programmes might change the girls’ self-image.
I Don’t Care Much as Long as I Am Also on Facebook
Authors: Nongpong Santika , Charoensukmongkol Peerayuth
Published: August 2016

This research investigated the impacts of social media use while being with a partner on the perception of relationship problems experienced by the other partner. The results from the partial least squares regression indicated that individuals who perceived that their partners used social media excessively tended to report a higher perception of lack of caring, loneliness, and jealousy. However, only lack of caring was found to be the key reason that significantly explained the intention to break up. In addition, the analysis of the moderating effect revealed interesting evidence showing that the perception of relationship problems associated with social media use of own partners appeared to be more severe for the respondents who reported that they used social media less intensively than their partners. Conversely, for the respondents who reported that they used social media to a greater degree than their partners, the impacts on the perceived relationship problems were significantly lessened.
Understanding the Experiences of Husbands in Step-Couples
Authors: Gold Joshua M.
Published: August 2016

The literature on stepfamily functioning pays far more attention to issues of stepparenting than issues of marital success. However, the marital bond is equally important to support stepparenting success and provide the couple with a solid foundation for the family once the stepchildren have departed. To date, any literature concerning stepfamily marriage seems concentrated on the experience of wives in stepfamilies, relegating the experiences of husbands to an afterthought. In an attempt to redress this oversight, this article provides insights into the challenges facing husbands in stepfamilies, with implications for clinicians seeking to strengthen the marital relationship in stepfamilies.