Design and feasibility testing of a novel group intervention for young women who binge drink in groups

BackgroundYoung women frequently drink alcohol in groups and binge drinking within these natural drinking groups is common. This study describes the design of a theoretically and empirically based group intervention to reduce binge drinking among young women. It also evaluates their engagement with the intervention and the acceptability of the study methods.MethodsFriendship groups of women aged 18–35 years, who had two or more episodes of binge drinking (>6 UK units on one occasion; 48g of alcohol) in the previous 30 days, were recruited from the community. A face-to-face group intervention, based on the Health Action Process Approach, was delivered over three sessions. Components of the intervention were woven around fun activities, such as making alcohol free cocktails. Women were followed up four months after the intervention was delivered. Results The target of 24 groups (comprising 97 women) was recruited. The common pattern of drinking was infrequent, heavy drinking (mean consumption on the heaviest drinking day was UK 18.1 units). Process evaluation revealed that the intervention was delivered with high fidelity and acceptability of the study methods was high. The women engaged positively with intervention components and made group decisions about cutting down. Twenty two groups set goals to reduce their drinking, and these were translated into action plans. Retention of individuals at follow up was 87%.ConclusionsThis study successfully recruited groups of young women whose patterns of drinking place them at high risk of acute harm. This novel approach to delivering an alcohol intervention has potential to reduce binge drinking among young women. The high levels of engagement with key steps in the behavior change process suggests that the group intervention should be tested in a full randomised controlled trial

Principles of genetic circuit design

Cells navigate environments, communicate and build complex patterns by initiating gene expression in response to specific signals. Engineers seek to harness this capability to program cells to perform tasks or create chemicals and materials that match the complexity seen in nature. This Review describes new tools that aid the construction of genetic circuits. Circuit dynamics can be influenced by the choice of regulators and changed with expression 'tuning knobs'. We collate the failure modes encountered when assembling circuits, quantify their impact on performance and review mitigation efforts. Finally, we discuss the constraints that arise from circuits having to operate within a living cell. Collectively, better tools, well-characterized parts and a comprehensive understanding of how to compose circuits are leading to a breakthrough in the ability to program living cells for advanced applications, from living therapeutics to the atomic manufacturing of functional materials.National Institute of General Medical Sciences (U.S.) (Grant P50 GM098792)National Institute of General Medical Sciences (U.S.) (Grant R01 GM095765)National Science Foundation (U.S.). Synthetic Biology Engineering Research Center (EEC0540879)Life Technologies, Inc. (A114510)National Science Foundation (U.S.). Graduate Research FellowshipUnited States. Office of Naval Research. Multidisciplinary University Research Initiative (Grant 4500000552

Human cytomegalovirus immediate-early 1 protein rewires upstream STAT3 to downstream STAT1 signaling switching an IL6-type to an IFNγ-like response

MN and CP were supported by the Wellcome Trust (www.wellcome.ac.uk) Institutional Strategic Support Fund and CP was supported by the Deutsche Forschungsgemeinschaft (PA 815/2-1; www.dfg.de).The human cytomegalovirus (hCMV) major immediate-early 1 protein (IE1) is best known for activating transcription to facilitate viral replication. Here we present transcriptome data indicating that IE1 is as significant a repressor as it is an activator of host gene expression. Human cells induced to express IE1 exhibit global repression of IL6- and oncostatin M-responsive STAT3 target genes. This repression is followed by STAT1 phosphorylation and activation of STAT1 target genes normally induced by IFNγ. The observed repression and subsequent activation are both mediated through the same region (amino acids 410 to 445) in the C-terminal domain of IE1, and this region serves as a binding site for STAT3. Depletion of STAT3 phenocopies the STAT1-dependent IFNγ-like response to IE1. In contrast, depletion of the IL6 receptor (IL6ST) or the STAT kinase JAK1 prevents this response. Accordingly, treatment with IL6 leads to prolonged STAT1 instead of STAT3 activation in wild-type IE1 expressing cells, but not in cells expressing a mutant protein (IE1dl410-420) deficient for STAT3 binding. A very similar STAT1-directed response to IL6 is also present in cells infected with a wild-type or revertant hCMV, but not an IE1dl410-420 mutant virus, and this response results in restricted viral replication. We conclude that IE1 is sufficient and necessary to rewire upstream IL6-type to downstream IFNγ-like signaling, two pathways linked to opposing actions, resulting in repressed STAT3- and activated STAT1-responsive genes. These findings relate transcriptional repressor and activator functions of IE1 and suggest unexpected outcomes relevant to viral pathogenesis in response to cytokines or growth factors that signal through the IL6ST-JAK1-STAT3 axis in hCMV-infected cells. Our results also reveal that IE1, a protein considered to be a key activator of the hCMV productive cycle, has an unanticipated role in tempering viral replication.Publisher PDFPeer reviewe

Early influences on cardiovascular and renal development

The hypothesis that a developmental component plays a role in subsequent disease initially arose from epidemiological studies relating birth size to both risk factors for cardiovascular disease and actual cardiovascular disease prevalence in later life. The findings that small size at birth is associated with an increased risk of cardiovascular disease have led to concerns about the effect size and the causality of the associations. However, recent studies have overcome most methodological flaws and suggested small effect sizes for these associations for the individual, but an potential important effect size on a population level. Various mechanisms underlying these associations have been hypothesized, including fetal undernutrition, genetic susceptibility and postnatal accelerated growth. The specific adverse exposures in fetal and early postnatal life leading to cardiovascular disease in adult life are not yet fully understood. Current studies suggest that both environmental and genetic factors in various periods of life may underlie the complex associations of fetal growth retardation and low birth weight with cardiovascular disease in later life. To estimate the population effect size and to identify the underlying mechanisms, well-designed epidemiological studies are needed. This review is focused on specific adverse fetal exposures, cardiovascular adaptations and perspectives for new studies. Copyrigh

Radiological manifestations and clinical findings of patients with oncologic and osteoporotic medication-related osteonecrosis of the jaw

Medication-related osteonecrosis of the jaw (MRONJ) poses a challenging form of osteomyelitis in patients undergoing antiresorptive therapies in contrast to conventional osteomyelitis. This study aimed to compare the clinical and radiological features of MRONJ between patients receiving low-dose medications for osteoporosis and those receiving high-dose medications for oncologic purposes. The clinical, panoramic radiographic, and computed tomography data of 159 patients with MRONJ (osteoporotic group, n = 120; oncologic group, n = 39) who developed the condition after using antiresorptive medications for the management of osteoporosis or bone malignancy were analyzed. The osteoporotic group was older (75.8 vs. 60.4 years, p < 0.01) and had a longer duration of medication usage than the oncologic group (58.1 vs. 28.0 months, p < 0.01). Pus discharge and swelling were more common in the osteoporotic group (p < 0.05), whereas bone exposure was more frequent in the oncologic group (p < 0.01). The mandibular cortical index (MCI) in panoramic radiographs was higher in the osteoporotic group (p < 0.01). The mean sequestra size was larger in the oncologic group than in the osteoporotic group (15.3 vs. 10.6 mm, p < 0.05). The cured rate was significantly higher in the osteoporotic group (66.3% vs. 33.3%, p < 0.01). Oncologic MRONJ exhibited distinct clinical findings including rapid disease onset, fewer purulent signs, and lower cure rates than osteoporotic MRONJ. Radiological features such as sequestrum size on CT scan, and MCI values on panoramic radiographs, may aid in differentiating MRONJ in osteoporotic and oncologic patients

Childhood emotional trauma and cyberbullying perpetration among emerging adults: a multiple mediation model of the role of problematic social media use and psychopathology

Research suggests that a small minority of social media users experience problems as a result of their online use. The purpose of the present study was to examine the association of cyberbullying perpetration and problematic social media use with childhood emotional trauma, Cluster B (narcissistic, histrionic, antisocial, and borderline) personality traits, dissociative experiences (DEs), depression, and self-esteem in a nonclinical undergraduate sample. A total of 344 university students volunteered to complete a questionnaire that included measures on the aforementioned dimensions. Thirty-eight percent of the participants had emotional neglect and 27% had emotional abuse, while 44% of them demonstrated at least one cyberbullying perpetration behavior. Results indicated that cyberbullying perpetrators had higher scores on problematic social media use, dissociative experiences, Cluster B traits, depression and childhood emotional trauma, and lower on self-esteem. Path analysis demonstrated that, while adjusting for gender and age, childhood emotional trauma was directly and indirectly associated with cyberbullying perpetration via Cluster B traits. Moreover, depression and dissociation were directly associated with problematic social media use. The findings of this study emphasize the important direct role of childhood emotional trauma and pathological personality traits on cyberbullying perpetration

Risk Prediction Model Based on Magnetic Resonance Elastography-Assessed Liver Stiffness for Predicting Posthepatectomy Liver Failure in Patients with Hepatocellular Carcinoma

BACKGROUND/AIMS: Posthepatectomy liver failure (PHLF) is a major complication that increases mortality in patients with hepatocellular carcinoma after surgical resection. The aim of this retrospective study was to evaluate the utility of magnetic resonance elastography-assessed liver stiffness (MRE-LS) for the prediction of PHLF and to develop an MRE-LS-based risk prediction model. METHODS: A total of 160 hepatocellular carcinoma patients who underwent surgical resection with available preoperative MRE-LS data were enrolled. Clinical and laboratory parameters were collected from medical records. Logistic regression analyses were conducted to identify the risk factors for PHLF and develop a risk prediction model. RESULTS: PHLF was present in 24 patients (15%). In the multivariate logistic analysis, high MRE-LS (kPa; odds ratio [OR] 1.49, 95% confidence interval [CI] 1.12 to 1.98, p=0.006), low serum albumin (-0.55; OR 3.72, 95% CI 1.15 to 12.04, p=0.028), and higher serum alpha-fetoprotein (>100 ng/mL; OR 3.53, 95% CI 1.20 to 10.40, p=0.022) were identified as independent risk factors for PHLF. A risk prediction model for PHLF was established using the multivariate logistic regression equation. The area under the receiver operating characteristic curve (AUC) of the risk prediction model was 0.877 for predicting PHLF and 0.923 for predicting grade B and C PHLF. In leave-one-out cross-validation, the risk model showed good performance, with AUCs of 0.807 for all-grade PHLF and 0. 871 for grade B and C PHLF. CONCLUSIONS: Our novel MRE-LS-based risk model had excellent performance in predicting PHLF, especially grade B and C PHLF

Milk feeding, solid feeding, and obesity risk:a review of the relationships between early life feeding practices and later adiposity

Childhood obesity is a major health issue with associated ill-health consequences during childhood and into later adolescence and adulthood. Given that eating behaviors are formed during early childhood, it is important to evaluate the relationships between early life feeding practices and later child adiposity. This review describes and evaluates recent literature exploring associations between child weight and the mode of milk feeding, the age of introducing solid foods and caregivers’ solid feeding practices. There are many inconsistencies in the literature linking early life feeding to later obesity risk and discrepancies may be related to inconsistent definitions, or a lack of control for confounding variables. This review summarizes the literature in this area and identifies the need for large scale longitudinal studies to effectively explore how early life feeding experiences may interact with each other and with nutritional provision during later childhood to predict obesity risk

Current routine practice and clinico-pathological characteristics associated with acute promyelocytic leukemia in Korea

Background: Acute promyelocytic leukemia (APL) can be life threatening, necessitating emergency therapy with prompt diagnosis by morphologic findings, immunophenotyping, cytogenetic analysis, or molecular studies. This study aimed to assess the current routine practices in APL and the clinico-pathologic features of APL. Methods: We reviewed the medical records of 48 Korean patients (25 men, 23 women; median age, 51 (20‒80) years) diagnosed with APL in 5 university hospitals between March 2007 and February 2012. Results: The WBC count at diagnosis and platelet count varied from 0.4 to 81.0 (median 2.0)×109/L and 2.7 to 124.0 (median 54.5)×109/L, respectively. The median values for prothrombin time and activated partial thromboplastin time were 14.7 (11.3‒44.1) s and 29 (24‒62) s, respectively. All but 2 patients (96%) showed a fibrin/fibrinogen degradation product value of ＞20 mg/mL. The D-dimer median value was 5,000 (686‒55,630) ng/mL. The t(15;17)(q22;q12 and PML-RARA fusion was found in all patients by chromosome analysis and/or multiplex reverse transcriptase-polymerase chain reaction (RT-PCR), with turnaround times of 8 (2‒19) d and 7 (2‒13) d, respectively. All patients received induction chemotherapy: all-trans retinoic acid (ATRA) alone (N=11, 26%), ATRA+idarubicin (N=25, 58%), ATRA+cytarabine (N=3, 7%), ATRA+idarubicin+cytarabine (N=4, 9%). Conclusion: Since APL is a medical emergency and an accurate diagnosis is a prerequisite for prompt treatment, laboratory support to implement faster diagnostic tools to confirm the presence of PML-RARA is required