Adolescent Binge Drinking Is Associated With Accelerated Decline of Gray Matter Volume.

The age- and time-dependent effects of binge drinking on adolescent brain development have not been well characterized even though binge drinking is a health crisis among adolescents. The impact of binge drinking on gray matter volume (GMV) development was examined using 5 waves of longitudinal data from the National Consortium on Alcohol and NeuroDevelopment in Adolescence study. Binge drinkers (n = 166) were compared with non-binge drinkers (n = 82 after matching on potential confounders). Number of binge drinking episodes in the past year was linked to decreased GMVs in bilateral Desikan-Killiany cortical parcellations (26 of 34 with P < 0.05/34) with the strongest effects observed in frontal regions. Interactions of binge drinking episodes and baseline age demonstrated stronger effects in younger participants. Statistical models sensitive to number of binge episodes and their temporal proximity to brain volumes provided the best fits. Consistent with prior research, results of this study highlight the negative effects of binge drinking on the developing brain. Our results present novel findings that cortical GMV decreases were greater in closer proximity to binge drinking episodes in a dose-response manner. This relation suggests a causal effect and raises the possibility that normal growth trajectories may be reinstated with alcohol abstinence.

Optimizing sleep across the menopausal transition.

Women frequently experience sleep disturbances, particularly night-time awakenings, as they transition menopause and enter postmenopause. Sleep is essential for optimal functioning and health. Persistent and distressing sleep disturbances across menopause can negatively impact daytime functioning and productivity, and increase risk for mental and physical health conditions. While multiple factors can disturb sleep, two unique factors in the context of menopause are vasomotor symptoms and the changing reproductive hormone environment. Vasomotor symptoms are associated with sleep disturbances and contribute significantly to awakenings and amount of time spent awake during the night. Even after accounting for vasomotor and depressive symptoms, lower estradiol and higher follicle stimulating hormone levels, indicative of menopause, are associated with sleep disturbance, particularly awakenings, suggesting that the hormone environment may directly affect sleep. Management strategies for clinically significant menopausal sleep disturbances include cognitive behavioral therapy for insomnia, which is effective and durable in treating menopausal insomnia. Hormone therapy alleviates sleep disturbances, particularly in the presence of disruptive vasomotor symptoms. Sleep disturbances have a significant impact on women's functioning and health, and there is a need for further research of the underlying mechanisms to advance effective preventative and treatment strategies that ensure optimal health and well-being of midlife women.

A pilot study to investigate the measurement of immunoglobulin A in Welsh Cob and Welsh Pony foals' faeces and their dam's milk.

Aims: To determine if an ELISA for measurement of IgA in equine serum could be used to measure concentrations of IgA in foal faeces and to determine correlations with concentrations in the milk of the dam.Methods: Faeces from 20 Welsh Cob and Welsh Pony foals and milk from their dams were collected within 12 hours (Day 0) and at 6 days after parturition (Day 6). On Day 6, faeces could not be collected from 2/20 foals, and milk samples could not be collected from 3/20 mares. An equine IgA ELISA validated for serum and plasma was used to measure concentrations of IgA in all samples in triplicate. The precision of the assay for each sample type was determined using modified CV.Results: IgA was not detectable in 7/20 Day 0 faecal samples and in 2/18 Day 6 faecal samples. For samples with detectable IgA, the mean modified CV was 10.5 (95% CI = 6.0-15.0)% for Day 0 faecal samples, and was 6.8 (95% CI = 4.3-9.4)% for Day 6 faecal samples. Median concentrations of IgA in faeces on Day 0 were lower than concentrations on Day 6 (0.7 mg/g vs. 37 mg/g dry matter; p = 0.003). Concentrations of IgA in milk and faeces on Day 6 were statistically correlated (r = 0.59; p = 0.006).Conclusions and clinical relevance: The IgA ELISA showed acceptable precision when used to estimate concentrations of IgA in foal faeces during the first week of life, but IgA could not be detected in 37% of meconium samples collected on Day 0. This assay may be useful for investigation of the role of maternal milk IgA in the gastrointestinal tract of neonatal foals, but further assessment of both accuracy and precision of the ELISA is required.

Cytomegalovirus: an unlikely ally in the fight against blood cancers?

Cytomegalovirus (CMV) infection is a potentially fatal complication in patients receiving haematopoietic stem cell transplantation (HSCT), but recent evidence indicates that CMV has strong anti-leukaemia effects due in part to shifts in the composition of natural killer (NK) cell subsets. NK cells are the primary mediators of the anti-leukaemia effect of allogeneic HSCT, and infusion of allogeneic NK cells has shown promise as a means of inducing remission and preventing relapse of several different haematological malignancies. The effectiveness of these treatments is limited, however, when tumours express human leucocyte antigen (HLA)-E, a ligand for the inhibitory receptor NKG2A, which is expressed by the vast majority of post-transplant reconstituted and ex-vivo expanded NK cells. It is possible to enhance NK cell cytotoxicity against HLA-Epos malignancies by increasing the proportion of NK cells expressing NKG2C (the activating receptor for HLA-E) and lacking the corresponding inhibitory receptor NKG2A. The proportion of NKG2Cpos /NKG2Aneg NK cells is typically low in healthy adults, but it can be increased by CMV infection or ex-vivo expansion of NK cells using HLA-E-transfected feeder cells and interleukin (IL)-15. In this review, we will discuss the role of CMV-driven NKG2Cpos /NKG2Aneg NK cell expansion on anti-tumour cytotoxicity and disease progression in the context of haematological malignancies, and explore the possibility of harnessing NKG2Cpos /NKG2Aneg NK cells for cancer immunotherapy.

Prevalence of Helicobacter pylori positivity in patients undergoing percutaneous coronary intervention.

BACKGROUND: The adverse effect of haemorrhagic complications after percutaneous coronary intervention (PCI) on outcome is well established with Helicobacter pylori infection known to be an important precipitant of peptic ulcer disease in patients receiving non-steroidal anti-inflammatory drug therapy. The prevalence of H. pylori positivity in patients undergoing PCI and receiving subsequent antiplatelet therapy is unknown. AIMS: We sought to determine the prevalence and features associated with H. pylori positivity in patients undergoing PCI. METHODS: All patients undergoing PCI between August 2008 and April 2009 were identified and assessed for H. pylori positivity with serological status determined by using a commercially supplied enzyme-linked immunosorbent assay. RESULTS: A total of 245 patients undergoing PCI during the study period had samples obtained for H. pylori serology. Of these, 91 were positive for H. pylori serology (37%) and 148 were negative (60%) with six samples being equivocal (3%). Of those patients positive for H. pylori, 75% were on agents at admission known to promote or precipitate gastrointestinal haemorrhage. Patients positive for H. pylori tended to be older, with increased creatinine and more likely to be receiving proton pump inhibitor therapy. CONCLUSIONS: In an unselected cohort of patients undergoing PCI in a single centre, we detected a prevalence of H. pylori positivity in 37% of patients; this denotes a potentially treatable precipitant of haemorrhage in a considerable portion of patients receiving dual antiplatelet therapy after PCI. Further prospective study is required to determine if the presence of H. pylori positivity is associated with adverse events in terms of gastrointestinal and cardiac outcomes.

Youth screen use in the ABCD® study.

Adolescent screen usage is ubiquitous and influences development and behavior. Longitudinal screen usage data coupled with psychometrically valid constructs of problematic behaviors can provide insights into these relationships. We describe methods by which the screen usage questionnaire was developed in the Adolescent Brain Cognitive Development (ABCD) Study, demonstrate longitudinal changes in screen usage via child report and describe data harmonization baseline-year 2. We further include psychometric analyses of adapted social media and video game addiction scales completed by youth. Nearly 12,000 children ages 9-10 years at baseline and their parents were included in the analyses. The social media addiction questionnaire (SMAQ) showed similar factor structure and item loadings across sex and race/ethnicities, but that item intercepts varied across both sex and race/ethnicity. The videogame addiction questionnaire (VGAQ) demonstrated the same configural, metric and scalar invariance across racial and ethnic groups, however differed across sex. Video gaming and online social activity increased over ages 9/10-11/12 (p's < 0.001). Compared with boys, girls engaged in greater social media use (p < .001) and demonstrated higher ratings on the SMAQ (p < .001). Compared with girls, boys played more video games (p < .001) and demonstrated higher ratings on the VGAQ (p < .001). Time spent playing video games increased more steeply for boys than girls from age 9/10-11/12 years (p < .001). Black youth demonstrated significantly higher SMAQ and VGAQ scores compared to all other racial/ethnic groups. These data show the importance of considering different screen modalities beyond total screen use and point towards clear demographic differences in use patterns. With these comprehensive data, ABCD is poised to address critical questions about screen usage changes across adolescence.

Ononis natrix L. Lowers the Blood Glucose Concentration in Wistar Rats with Streptozotocin-induced Diabetes Mellitus.

BACKGROUND: Practitioners of traditional medicine use the decoction of Ononis natrix L. to treat hyperglycemia. The literature offers no evidence to support the use. OBJECTIVE: To investigate the effect of the decoction of Ononis natrix L. on the blood glucose concentration in Wistar rats (Rattus norvegicus) with streptozotocin-induced diabetes mellitus. METHODS: We obtained 35 Wistar rats from the animal colony of The University of Jordan School of Medicine. We induced diabetes by a single intraperitoneal injection of streptozotocin (60 mg/kg body weight) and 23 rats (66%) survived to allocation. We randomly assigned the rats to one of four groups: negative control (1% Tween 80 in distilled water), positive control (100 mg/kg metformin), high-dose treatment (7.5 mL of the decoction), and low-dose treatment (3.5 mL of the decoction). We administered the doses twice daily by oral gavage for two weeks and measured the tailblood glucose concentration twice daily, once before the first dose and another time after the second dose. We used linear mixed-effects regression to model the change in blood glucose concentration as a function of the experimentation groups, with adjustments for pseudoreplication and temporal variation. RESULTS: The estimated mean change was 1 mmol/L (-30 to 31 mmol/L) for the negative control group, -26 mmol/L (-56 to 5 mmol/L) for the positive control group, -75 mmol/L (-108 to -42) for the low-dose treatment group, and -82 mmol/L (-111 to -53 mmol/L) for the high-dose treatment group. CONCLUSION: In conclusion, we demonstrate, for the first time, the hypoglycemic effect of Ononis natrix L. in an animal model of diabetes.

Baseline brain function in the preadolescents of the ABCD Study.

The Adolescent Brain Cognitive Development (ABCD) Study® is a 10-year longitudinal study of children recruited at ages 9 and 10. A battery of neuroimaging tasks are administered biennially to track neurodevelopment and identify individual differences in brain function. This study reports activation patterns from functional MRI (fMRI) tasks completed at baseline, which were designed to measure cognitive impulse control with a stop signal task (SST; N = 5,547), reward anticipation and receipt with a monetary incentive delay (MID) task (N = 6,657) and working memory and emotion reactivity with an emotional N-back (EN-back) task (N = 6,009). Further, we report the spatial reproducibility of activation patterns by assessing between-group vertex/voxelwise correlations of blood oxygen level-dependent (BOLD) activation. Analyses reveal robust brain activations that are consistent with the published literature, vary across fMRI tasks/contrasts and slightly correlate with individual behavioral performance on the tasks. These results establish the preadolescent brain function baseline, guide interpretation of cross-sectional analyses and will enable the investigation of longitudinal changes during adolescent development.

Substance use patterns in 9-10 year olds: Baseline findings from the adolescent brain cognitive development (ABCD) study.

BACKGROUND: The Adolescent Brain Cognitive Development ™ Study (ABCD Study®) is an open-science, multi-site, prospective, longitudinal study following over 11,800 9- and 10-year-old youth into early adulthood. The ABCD Study aims to prospectively examine the impact of substance use (SU) on neurocognitive and health outcomes. Although SU initiation typically occurs during teen years, relatively little is known about patterns of SU in children younger than 12. METHODS: This study aims to report the detailed ABCD Study® SU patterns at baseline (n = 11,875) in order to inform the greater scientific community about cohort's early SU. Along with a detailed description of SU, we ran mixed effects regression models to examine the association between early caffeine and alcohol sipping with demographic factors, externalizing symptoms and parental history of alcohol and substance use disorders (AUD/SUD). PRIMARY RESULTS: At baseline, the majority of youth had used caffeine (67.6 %) and 22.5 % reported sipping alcohol (22.5 %). There was little to no reported use of other drug categories (0.2 % full alcohol drink, 0.7 % used nicotine, <0.1 % used any other drug of abuse). Analyses revealed that total caffeine use and early alcohol sipping were associated with demographic variables (p's<.05), externalizing symptoms (caffeine p = 0002; sipping p = .0003), and parental history of AUD (sipping p = .03). CONCLUSIONS: ABCD Study participants aged 9-10 years old reported caffeine use and alcohol sipping experimentation, but very rare other SU. Variables linked with early childhood alcohol sipping and caffeine use should be examined as contributing factors in future longitudinal analyses examining escalating trajectories of SU in the ABCD Study cohort.

Slow virus kidney disease of mice.

Preliminary observations based on organ weight differential, renal function, and glomerular lesions in mice infected neonatally with lymphocytic choriomeningitis indicate the presence of a slow virus-induced kidney disease of mice. This condition is accompanied by a marked decrease in the size of the kidneys, with progressive diminution of renal function, as shown by measurements of creatinine and urea clearance.

Extracellular recordings from human retinal ganglion cells.

Ganglion cells were studied in the isolated retina, with extracellular recordings. Activity was found similar to that seen in the retinas of other animal species.

Alkaline hydrogen peroxide treatment unlocks energy in agricultural by-products.

Lignocellulosic residues (wheat straw, corncobs, and cornstalks) were treated with a dilute alkaline solution of hydrogen peroxide and suspended in cattle rumen in situ to measure microbial degradation. The rate and extent of dry matter disappearance were markedly increased as a result of the treatment. Results in vivo indicate that this treatment increases the fermentability of wheat straw structural carbohydrates such that this agricultural by-product may be considered an acceptable energy source for the ruminant animal. Treatment of wheat straw allowed more complete bacterial colonization and more rapid degradation of the cell wall.

Identification of a juvenile hormone-like compound in a crustacean.

Juvenile hormone (JH) has central roles in the regulation of insect development and reproduction but has not previously been identified in other arthropod classes. The hemolymph of a crustacean, Libinia emarginata (Leach), has now been analyzed for JH-like compounds. Samples contained 0.003 to 0.030 nanogram of JH III per milliliter and 10 to 50 nanograms of methyl farnesoate per milliliter; methyl farnesoate is a compound structurally related to JH III that has JH bioactivity. Several tissues were examined for synthesis and secretion of JH-like compounds. Of these tissues, only the mandibular organs produced and secreted JH III and methyl farnesoate. However, microchemical analysis revealed that this JH III was racemic, and thus likely an artifactual oxidation product of methyl farnesoate. Secretion of methyl farnesoate was related to reproduction in females, with the highest rates observed in Libinia near the end of the ovarian cycle when oocyte growth and vitellogenesis are greatest. These results indicate that JH-like compounds such as methyl farnesoate have regulatory roles in crustaceans.

HPV test by Hybrid Capture II for the diagnosis of HR-HPV persistent infection.

INTRODUCTION: Persistent high-risk HPV (HR-HPV) infection is associated with a greater risk of cervical cancer. PATIENTS AND METHODS: Statistical data on the prevalence of HR-HPV infections in the Algerian population is lacking. We conducted a prospective study of 300 women aged between 25 and 50 years, screened for cervical cancer from 2012 to 2015 in Sidi Bel Abbès, a western region of Algeria. We aimed to assess the reliability of the repeated use of the HC II test (three longitudinal HPV tests 9 months apart from each other) in diagnosing the persistence of HR-HPV infection. RESULTS: The prevalence of HR-HPV infection was 7.33% and infected women were aged 37.9±3years. For 90.9% of HR-HPV-positive patients, the infection persisted for a mean of 18.5months [95% CI: 16.9-22.1months]. Among these patients, 55.55% developed CIN1 and 11.11% developed CIN2. The sensitivity of the HC II test was 81.74% [95% CI: 71.3-89.6] and its positive predictive value associated with abnormal cervical biopsy was 27.49% [95% CI: 16.0-33.33]. CONCLUSION: Repeating the HC II test is a good predictor for identifying women at high risk of cervical cancer.

In vitro activity of bleomycin, tallysomycin S10b, and liblomycin against fresh human tumor cells.

The objective of this study was to compare the relative in vitro cytotoxicity of bleomycin to that of two newer-generation analogues, tallysomycin S10b and liblomycin. The latter compound is of particular interest as it has recently been shown in preclinical studies to be free of a potential to cause pulmonary injury and yet to possess only a minor potential to produce myelotoxicity. Using the adhesive tumor cell culture system, we evaluated the activity of these three drugs against a panel of 13 human tumors of various types. The range of concentrations chosen was determined and normalized using a nonleukemic permanent mouse hematopoietic progenitor cell line. Those drug concentrations achieving 90% inhibition of growth (IC90) against the murine cell line were: 6.11 microM bleomycin; 7.53 microM tallysomycin S10b; and 0.6 microM liblomycin. When tested against fresh human tumors at equally myelotoxic IC90 concentrations, bleomycin and tallysomycin S10b (nonmyelotoxic compounds) both achieved 90% growth inhibition of all tumors, while liblomycin (a myelotoxic compound) produced an IC90 inhibition in 69% of all tumors. A comparison of drug IC90 values against individual fresh tumors indicated a correlation between bleomycin and its structurally related analogue tallysomycin S10b. No such correlation, however, was seen with liblomycin in comparison to either bleomycin or tallysomycin S10b. The relative activity of liblomycin versus that of bleomycin and tallysomycin S10b varied with individual tumors tested. The response rate of liblomycin, a myelotoxic compound within this normalized range, appears promising. These data represent the first comparison of liblomycin to bleomycin against a spectrum of fresh human tumors using a stem cell assay technique.

cis-Diamminedichloroplatinum(II)-induced sister chromatid exchange: an indicator of sensitivity and heterogeneity in primary human tumor cell cultures.

The effect of cis-diamminedichloroplatinum(II) (cPt) on sister chromatid exchange (SCE) induction was determined in 13 human primary tumor cell cultures. Primary cultures were derived from surgical specimens of solid tumors composed of a variety of histologies. Three to 16 days after biopsy, depending on the growth rate, cultures were treated with graded concentrations of cPt for 1 h and the SCE assay was performed. SCE dose-response curves (SCEs induced per chromosome versus cPt concentration) showed a wide range in cPt sensitivities that was not dependent on histology. SCE frequency histograms showed that several of the primary cultures contained both cPt-sensitive and -resistant cells. For six of the cultures, the SCEs induced per chromosome at 15 microM cPt were plotted versus the IC90 determined from a survival assay. A line fit to those points yielded a correlation coefficient of -0.74. These results show a relationship between the activity of cPt in the SCE assay and in the survival assay, which suggests that SCE analysis may be useful for predicting cPt sensitivity. In addition, characterization of cellular heterogeneity in cPt sensitivity using the SCE assay may provide additional information useful in the prediction of tumor response to treatment.

Antitumor activity against human tumor samples of cis-diamminedichloroplatinum(II) and analogues at equivalent in vitro myelotoxic concentrations.

We compared the antitumor activity of cis-diamminedichloroplatinum(II) (cisplatin; CDDP) with three CDDP analogues: cis-diammine-1,1-cyclobutanedicarboxylateplatinum(II) (CBDCA), N-methyliminodiacetato-1,2-diamino(cyclohexane)platinum(II) (MIDP), and N-(2-hydroxyethyl)-iminodiacetato-1,2-diamino(cyclohexane)platinum (II) (HIDP). Fresh human tumor samples in the adhesive tumor culture system were utilized for this comparison. The equitoxic concentrations of all four drugs were derived based on their inhibitory activity against human bone marrow samples. For these normalized concentrations, CDDP proved to have a higher cytotoxic activity than its analogues. CBDCA's in vitro activity had a significant correlation with CDDP activity (r = 0.67) in vitro. However, the structurally similar substances MIDP and HIDP demonstrated a much greater degree of association (r = 0.90). Our data suggest that CBDCA, HIDP, and MIDP have overall less activity than CDDP when tested at equitoxic in vitro concentrations. Close association between CDDP and CBDCA also reflects known clinical experience with these two drugs, suggesting the method of comparison used here is probably appropriate. These conclusions, however, must be validated by clinical trials.

Drug and radiation sensitivity measurements of successful primary monolayer culturing of human tumor cells using cell-adhesive matrix and supplemented medium.

The limitations of the agar suspension culture method for primary culturing of human tumor cells prompted development of a monolayer system optimized for cell adhesion and growth. This method grew 83% of fresh human tumor cell biopsy specimens, cultured and not contaminated, from a heterogeneous group of 396 tumors including lung cancer (93 of 114, 82%); melanoma (54 of 72, 75%); sarcoma (46 of 59, 78%); breast cancer (35 of 39, 90%); ovarian cancer (16 of 21, 76%); and a miscellaneous group consisting of gastrointestinal, genitourinary, mesothelioma, and unknown primaries (78 of 91, 86%). Cell growth was characterized morphologically with Papanicolaoustained coverslip cultures and cytogenetically with Giemsastained metaphase spreads. Morphological features such as nuclear pleomorphism, chromatin condensation, basophilic cytoplasm, and melanin pigmentation were routinely seen. Aneuploid metaphases were seen in 90% of evaluable cultures, with 15 of 28 showing 70% or more aneuploid metaphases. Colony-forming efficiency ranged between 0.01 and 1% of viable tumor cells, with a median efficiency of 0.2%. This culture system uses a low inoculum of 25,000 viable cells per well which permitted chemosensitivity testing of nine drugs at four doses in duplicate from 2.2 X 10(6) viable tumor cells and radiation sensitivity testing at five doses in quadruplicate from 0.6 X 10(6) cells. Cultures were analyzed for survival by computerized image analysis of crystal violet-stained cells. Drug sensitivity studies showed variability in sensitivity and in survival curve shape with exponential cell killing for cisplatin, Adriamycin, and etoposide, and shouldered survival curves for 5-fluorouracil frequently seen. Radiation sensitivity studies also showed variability in both sensitivity and survival curve shape. Many cultures showed exponential cell killing, although others had shouldered survival curves. This method for growing cells from primary human biopsy specimens is more efficient than the agar culture method, enables easier and better biological analysis of the actual cells grown, and permits improved characterization of drug and radiation survival curves.

Biological effect of epidermal growth factor on the in vitro growth of human tumors.

The effect of epidermal growth factor (EGF) on the in vitro growth of 186 malignant human tumor specimens (45 melanomas, 32 sarcomas, and 56 lung, 16 gynecological, 14 breast, 12 genitourinary, and 11 gastrointestinal carcinomas) was evaluated in the cellular adhesive matrix human tumor culture system supplemented with transferrin, insulin, hydrocortisone, and estradiol. EGF increased tumor growth by at least 50% in 81% of the 186 tumors and by over 100% in 54%. The enhanced growth induced by EGF was related to an accelerated cellular division independent of tumor type and not to an increase in the actual number of clonogenic units. The drug concentrations of cell cycle-independent Adriamycin and cisplatin needed to achieve a 90% tumor cell kill were not altered by the responsiveness of the tumor to EGF.

Involvement of chromosome 7 in primary lung tumor and nonmalignant normal lung tissue.

By using the newly developed adhesive tumor cell culture system, we analyzed the chromosomal constitutions of primary lung tumor and nonmalignant normal lung tissue from 10 previously untreated patients with non-small cell lung cancer. Chromosomal analyses were successfully carried out in banded chromosome preparations from 10 tumor and 8 normal lung tissue samples. All analyzed tumor and normal lung tissue samples had a predominantly normal diploid chromosome number. However, there was at least one structural or numerical alteration in every tumor and lung tissue sample analyzed. Chromosomes 1, 3, 4, 6, 7, 8, 9, 12, 15, and 20 were more often involved in rearrangement. The most consistent finding was trisomy 7; 4 patients had trisomy 7 in both tumor and normal lung tissue, and another 2 had this anomaly in tumor tissue only. Of the 4 patients without trisomy 7, 2 had a homogeneously staining region in the short arm of chromosome 7 in tumor tissue. Phytohemagglutinin-stimulated peripheral blood lymphocytes from 7 patients, including 5 patients with trisomy 7 in tumor tissue, did not show trisomy 7. These cytogenetic data suggest that chromosome 7 may be associated with lung cancer development and that trisomy 7 may be the hallmark of premalignant changes, at least in a subgroup of patients with non-small cell lung cancer.