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Heart transplantation is an established treatment for end-stage heart failure. Due to the increase in demand and persistent scarcity of organ, mechanical circulatory devices have played a major role in therapy for advanced heart failure. Usage of left ventricular assist device (LVAD) has gone up from 6% in 2006 to 43% in 2013 as per the United Network of Organ Sharing database. Majority of patients presenting for a heart transplantation are often bridged with an assist device prior for management of heart failure while on wait-list. On one hand, it is well established that LVADs improve survival on wait-list; on the other hand, the effect of LVAD on morbidity and survival after a heart transplantation is still unclear. In this article, we review the available literature and attempt to infer the outcomes given the risks and benefits of heart transplantation with prior LVAD patients.

This study examines associations between two measures of impulsivity and brain response to alcohol taste cues. Impulsivity is both a risk factor for and a consequence of alcohol use and misuse. Frontostriatal circuits are linked to both impulsivity and addiction-related behaviors, including response to alcohol cues. Non-treatment-seeking heavy drinkers (n = 55) completed (i) an fMRI alcohol taste cue-reactivity paradigm; (ii) the monetary choice questionnaire (MCQ), a measure of choice impulsivity where participants choose between smaller, sooner rewards and larger, delayed rewards; (iii) and the UPPS-P Impulsive Behavior Scale, a self-report measure assessing five impulsivity factors. General linear models identified associations between neural alcohol taste cue-reactivity and impulsivity, adjusting for age, gender, and smoking status. Self-reported sensation seeking was positively associated with alcohol taste cue-elicited activation in frontostriatal regions, such that individuals who reported higher sensation seeking displayed greater neural response to alcohol taste cues. Conversely, delay discounting was negatively associated with activation in frontoparietal regions, such that individuals who reported greater discounting showed less cue-elicited activation. There were no significant associations between other self-reported impulsivity subscales and alcohol taste cue-reactivity. These results indicate that sensation seeking is associated with reward responsivity, while delay discounting is associated with recruitment of self-control circuitry., (Copyright © 2019. Published by Elsevier B.V.)

The 3-dimensional implant position is critical in achieving a successful surgical and prosthetic outcome for an implant-supported restoration. In an edentulous mandibular arch, the lack of neighboring reference points and the nature of the resorptive process make ideal surgical implant placement difficult to achieve. As the edentulous mandibular ridge resorbs lingually and apically, the ideal prosthetic tooth positions often may be located facial to the ridge crest. Achieving proper implant position requires use of a guide that takes into consideration the location of the existing ridge in addition to ideal tooth position. This article describes the use of an adaptable, metal, linked implant position guide that utilizes interimplant spacing of 5 mm, 7 mm, or 9 mm between adjacent tooth positions throughout the arch to aid in keeping adjacent implants parallel and symmetrical to the contralateral side while also respecting the ideal natural tooth dimensions and occlusion. The use of the guide is demonstrated in three cases of mandibular edentulism.

Background: Despite known genetic variation across races, studies examining pharmacogenetics of a single nucleotide polymorphism (SNP) of the mu-opioid receptor gene (OPRM1) on clinical response to naltrexone have been conducted in predominantly Caucasian samples. Evidence is mixed for pharmacogenetic OPRM1 and naltrexone effects on neural responses to alcohol cues. The current study tests the pharmacogenetic effects of naltrexone and OPRM1 on neural responses to alcohol taste cues in heavy drinkers of East Asian descent., Methods: Participants (N = 41) completed two double-blinded and counterbalanced functional magnetic resonance imaging (fMRI) sessions: one after taking naltrexone (50 mg/day) for four days and one after taking placebo for four days. Following titration, participants completed an fMRI alcohol taste-cues task. Analyses tested effects of naltrexone, OPRM1, and their interaction in whole-brain and region of interest (ROI) analyses of functional activation and functional connectivity in response to alcohol versus water taste cues., Results: We found no effects of naltrexone orOPRM1 on neural activation in whole-brain and ROI analyses, which included left and right ventral striatum (VS), anterior cingulate cortex (ACC), and orbitofrontal cortex (OFC). Naltrexone increased functional connectivity between left VS and clusters in medial prefrontal cortex, posterior cingulate gyrus, as well as right VS and occipital cortex, compared to placebo., Conclusions: Naltrexone treatment enhanced functional connectivity in a key reinforcement-related pathway during alcohol versus water taste cues, corroborating neuroimaging work with other substances. Null medication and pharmacogenetics effects on functional activation add to a mixed naltrexone literature and may underscore the modest size of these effects in East Asians., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Brief interventions represent a promising psychological intervention targeting individuals with heavy alcohol use. Motivation to change represents an individual's openness to engage in a behavior change strategy and is thought to be a crucial component of brief interventions. Neuroimaging techniques provide a translational tool to investigate the neurobiological mechanisms underlying potential mediators of treatment response, including motivation to change. Therefore, this study aimed to examine the effect of a brief intervention on motivation to change drinking behavior and neural alcohol taste cue reactivity. Methods: Non-treatment-seeking heavy drinkers were randomized to receive a brief drinking intervention (n = 22) or an attention-matched control (n = 24). Three indices of motivation to change were assessed at baseline and after the intervention or control session: importance, confidence, and readiness. Immediately following the intervention or control session, participants also underwent an functional magnetic resonance imaging (fMRI) during which they completed an alcohol taste cues paradigm. Results: There was a significant effect of the brief intervention on increasing ratings of importance of changing drinking behavior, but not on ratings of confidence or readiness to change. Ratings of importance after the intervention or control session were associated with neural alcohol taste cue reactivity, but notably, this effect was only significant for participants who received the intervention. Individuals in the intervention condition showed a positive association between ratings of importance and activation in the precuneus, posterior cingulate, and insula. Conclusions: The brief drinking intervention was successful at improving one dimension of motivation to change among non-treatment-seeking heavy drinkers. The brief intervention moderated the relationship between ratings of importance and brain activation in circuitry associated with interoceptive awareness and self-reflection. Together, findings represent an initial step toward understanding the neurobiological mechanisms through which a brief intervention may improve motivation to change.

Naltrexone has been extensively studied for the treatment of alcohol use disorder. However, less is known about the effects of naltrexone on smoking outcomes in the context of alcohol use among East Asian individuals who have been suggested to differ in response to alcohol and to naltrexone. The present study is a secondary analysis that used a double-blind placebo-controlled design (n = 31) to examine the (a) effects of alcohol on basal craving for cigarettes, (b) effects of naltrexone on cigarette craving and alcohol craving during alcohol administration, and (c) relationship between craving for alcohol and cigarettes. Heavy drinking smokers of East Asian descent completed two counterbalanced intravenous alcohol administration sessions, one after taking naltrexone (50 mg) for five days and one after taking a placebo for five days. Self-reported subjective craving for cigarettes and for alcohol was recorded during each experimental session. Craving for cigarettes and alcohol increased significantly throughout the intravenous alcohol administration. A significant breath alcohol concentration (BrAC) × Medication interaction revealed that naltrexone blunted cigarette craving during alcohol administration, compared to placebo. Naltrexone significantly reduced craving for alcohol during alcohol administration in this group of heavy drinking smokers. Alcohol craving significantly predicted cigarette craving, however this effect did not vary across rising alcohol administration or by medication. These findings demonstrate that naltrexone reduces the urge to smoke and to drink during alcohol administration. Clinical studies are needed to further ascertain whether naltrexone may be of benefit to this distinct subgroup of heavy drinking smokers. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Background: Despite a rich literature on human laboratory paradigms of subjective response (SR) to alcohol, craving for alcohol, and alcohol self-administration, few studies have examined the interplay across these 3 constructs. The present study addresses this gap in the literature by examining the interplay between SR, craving, and self-administration in the human laboratory., Methods: Data were culled from a medication study (NCT02026011) in which heavy drinking participants of East Asian ancestry completed 2 double-blinded and counterbalanced experimental sessions. In each experimental session, participants received a priming dose of intravenous (IV) alcohol to a target breath alcohol concentration (BrAC) of 0.06 g/dl and measures of SR (stimulation and sedation) and alcohol craving were collected across rising BrACs. The IV alcohol challenge was immediately followed by a 1-hour alcohol self-administration period., Results: Mixed model analyses found a positive and significant relationship between the slope of stimulation and the slope of craving during the alcohol challenge. The relationship between sedation and craving, however, was not significant. The slope of craving during the alcohol challenge significantly predicted a higher number of mini-drinks consumed and lower latency to first drink. Further, mediation analyses found that craving was a significant mediator of the relationship between stimulation and total number of mini-drinks consumed, but the same pattern was not found for sedation., Conclusions: Insofar as alcohol self-administration represents the end point of interest for a host of experimental and clinical research questions, the present study suggests that alcohol craving represents a more proximal predictor of self-administration than measures of alcohol-induced stimulation. It is recommended that human laboratory models interpret measures of SR and craving in light of their relative predictive utility for drinking outcomes., (© 2019 by the Research Society on Alcoholism.)

To address the instability and repulsive interaction of carbon nanotubes (CNTs) in Li-ion batteries, mixed polymers (polyacrylonitrile and polyvinylpyrrolidone) were employed as matrix support to ensure that CNT particles remain in place during charge/discharge process and prevent particle migration. Various CNT-based anodes have been reported, but these require metal support that could result in contact resistance. Hence, free-standing CNT electrodes are an attractive option. A simple method of electrospinning polymers and calcination at 800 °C is presented with CNT loading as high as 50 wt % can be obtained without binder and acts as main active material rather than an additive as described in previous studies. The anode [pyrolyzed polymer (PP)-CNT] showed excellent performance with a high discharge specific capacity of 960 mA h/g at a current density of 200 mA/g. The capacity at a higher current density (1600 mA/g) remained greater than graphite (372 mA h/g) at 521 mA h/g and showed a high stability for 675 cycles without exhibiting any significant capacity loss with a Coulombic efficiency of >95%. A rate capability experiment showed the reversibility of PP-CNTs after subjecting them to an increasing current density and regaining >95% of the initial capacity at a low current density (200 mA/g). The high capacitive performance of the material is attributed to the high loading of CNTs and their containment within the bulk of the polymer matrix to prevent particle migration and agglomeration as well as the capacity of the nanofibers to preserve a tight proximity of the electrolyte-electrode interface., Competing Interests: The authors declare no competing financial interest.

Background: Brief interventions have empirical support for acutely reducing alcohol use among non-treatment-seeking heavy drinkers. Neuroimaging techniques allow for the examination of the neurobiological effect of behavioral interventions, probing brain systems putatively involved in clinical response to treatment. Few studies have prospectively evaluated whether psychosocial interventions attenuate neural cue reactivity that in turn reduces drinking in the same population. This study aimed to examine the effect of a brief intervention on drinking outcomes, neural alcohol cue reactivity, and the ability of neural alcohol cue reactivity to prospectively predict drinking outcomes., Methods: Non-treatment-seeking heavy drinking participants were randomized to receive a brief interview intervention (n = 22) or an attention-matched control (n = 24). Immediately following the intervention or control, participants underwent a functional magnetic resonance imaging scan comprised of the alcohol taste cues paradigm. Four weeks after the intervention (or control), participants completed a follow-up visit to report on their past-month drinking. Baseline and follow-up percent heavy drinking days (PHDD) were calculated for each participant., Results: There was no significant effect of the brief intervention on PHDD at follow-up or on modulating neural activation to alcohol relative to water taste cues. There was a significant association between neural response to alcohol taste cues and PHDD across groups (Z > 2.3, p < 0.05), such that individuals who had greater neural reactivity to alcohol taste cues in the precuneus and prefrontal cortex (PFC) had fewer PHDD at follow-up., Conclusions: This study did not find an effect of the brief intervention on alcohol use in this sample, and the intervention was not associated with differential neural alcohol cue reactivity. Nevertheless, greater activation of the precuneus and PFC during alcohol cue exposure predicted less alcohol use prospectively suggesting that these neural substrates subserve the effects of alcohol cues on drinking behavior., (© 2018 by the Research Society on Alcoholism.)

Background: Alcohol use disorder (AUD) and its associated consequences remain significant public health concerns. Given that AUD represents a spectrum of severity, treatment options represent a continuum of care, ranging from single-session brief interventions to more intensive, prolonged, and specialized treatment modalities., Objective: This qualitative literature review seeks to describe the best practices for AUD by placing a particular emphasis on identifying those practices which have received the most empirical support., Method: This review summarizes psychological and pharmacological intervention options for AUD treatment, with a focus on the relapse prevention phase of recovery. Psychological and pharmacological treatments are summarized in terms of the empirical evidence favoring each approach and the level of AUD severity for which they are most indicated., Scientific Significance: One of the broad assertions from this review is that while AUD is highly prevalent, seeking treatment for AUD is not. There are a myriad of behavioral and pharmacological treatments that have shown compelling evidence of efficacy for the treatment of AUD. In the behavioral treatment literature, cognitive behavioral therapy has received the most consistent support. Opioid antagonism (via naltrexone) has been the most widely studied pharmacotherapy and has produced moderate effect sizes. While none of the treatments reviewed herein represents a so-called silver bullet for AUD, they each have the potential to significantly improve the odds of recovery. Precision medicine, or the identification of best treatment matches for individual patients, looms as an important overarching goal for the field, although specific matches are not yet sufficiently reliable in their empirical evidence to warrant clinical dissemination.

Objective: Heavy drinking smokers experience significant difficulties with smoking cessation. Craving is closely tied to relapses during cessation attempts, and alcohol consumption increases cigarette craving among heavy drinking smokers. To date, however, few moderators of the relationship between craving and relapse have been identified. Individuals' capacity for distress tolerance predicts smoking cessation outcomes and may be connected to craving. Relatedly, pharmacotherapies like varenicline and naltrexone reduce cigarette and alcohol cravings, respectively. No studies have examined the interrelationships among distress tolerance, craving, and pharmacotherapy effects. This study therefore examines distress tolerance as a moderator of the relationship between overnight abstinence-induced cigarette craving and subsequent alcohol- and cigarette-induced changes in craving among heavy drinking smokers. This study also examines the impact of varenicline and naltrexone on these relationships., Method: A total of 120 non-treatment-seeking heavy drinking smokers were randomized and titrated to one of the following conditions: (a) placebo, (b) varenicline, (c) naltrexone, or (d) varenicline + naltrexone. Participants then completed a laboratory paradigm after overnight abstinence that included consumption of alcohol (target .06 g/dl breath alcohol concentration) and one cigarette. Craving was assessed as abstinence-induced (Time 1), alcohol-induced (Time 2), and cigarette-induced (Time 3)., Results: Within varenicline + naltrexone, low distress tolerance individuals exhibited higher increases from abstinence- to alcohol-induced cigarette craving relative to high distress tolerance individuals. Across medications, low distress tolerance individuals reported flatter decreases from abstinence- to cigarette-induced cigarette craving relative to high distress tolerance individuals., Conclusions: Distress tolerance may differentially predict alcohol-induced cigarette craving when titrated to pharmacotherapy, as well as moderate decreases in craving after cigarette consumption. Future exploration of the identified interactive effects could elucidate specific conditions in which cravings are more proximally related to abstinence-induced smoking.

Background: There is evidence that regular cannabis use has negative effects on sleep health. Relative to HIV- populations, HIV + individuals consistently report greater sleep impairments. The number of HIV + individuals reporting frequent cannabis use, often to treat sleep issues, has significantly increased recently. It is unknown, however, if HIV status moderates the association between cannabis use and sleep health. The current study, therefore, examines these associations in a sample of HIV + and HIV- adults., Methods: HIV + and HIV- (N = 107) individuals completed one laboratory visit. Participants completed a 30-day drug use history questionnaire quantifying consumption of cannabis, cigarettes, and alcohol, and a sleep health questionnaire. To verify substance use and HIV status, participants completed a urine toxicology screening and serology testing., Results: HIV + individuals demonstrated lower sleep health than HIV- individuals. Linear regressions indicated that HIV status moderated the association between total 30-day cannabis consumption and sleep health; cannabis consumption was negatively associated with sleep health in HIV-, but not HIV + individuals. This interactive effect was significant after examining cigarette/alcohol use, depression symptoms, and demographic variables as covariates., Conclusions: These results corroborate studies demonstrating an inverse relationship between sleep health and cannabis consumption. This study also suggests that factors other than cannabis may be associated with lower sleep health in HIV + individuals. Emerging studies suggest that inflammation may mediate effects of cannabis on HIV infection. Future studies examining this mechanism are warranted to understand cannabis further and sleep in HIV + individuals., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: To estimate the magnitude of the correlation between neonatal outcomes of twins and demonstrate how this information can be used in the design of randomised controlled trials (RCTs) in women with twin pregnancies., Design: Secondary analysis of data from 12 RCTs., Setting: Obstetric care in multiple countries, 2004-2012., Population or Sample: 4504 twin pairs born to women who participated in RCTs to assess treatments given during pregnancy., Methods: Intraclass correlation coefficients (ICCs) were estimated using log-binomial and linear models., Main Outcome Measures: Perinatal death, respiratory distress syndrome, bronchopulmonary dysplasia, intraventricular haemorrhage, necrotising enterocolitis, sepsis, neonatal intensive care unit admission, birthweight, low birthweight and two composite measures of adverse neonatal outcome., Results: ICCs for the composite measures of adverse neonatal outcome were all above 0.5, indicating moderate to strong correlation between adverse outcomes of twins. For individual neonatal outcomes, median ICCs across trials ranged from 0.13 to 0.79 depending on the outcome. An example illustrates how ICCs can be used in sample size calculations for RCTs in women with twin pregnancies., Conclusions: The correlation between neonatal outcomes of twins varies considerably between outcomes and may be lower than expected. Our ICC estimates can be used for designing and analysing RCTs that recruit women with twin pregnancies and for performing meta-analyses that include such RCTs. Researchers are encouraged to report ICCs for neonatal outcomes in twins in their own RCTs., Tweetable Abstract: Correlation between neonatal outcomes of twins depends on the outcome and may be lower than expected., (© 2018 Royal College of Obstetricians and Gynaecologists.)

STEAP2 is a member of the Six-Transmembrane Epithelial Antigen of the Prostate (STEAP) protein family that is proposed to function as metalloreductase. While STEAP2 shows a complex subcellular distribution pattern localizing to both secretory and endocytic pathway organelles, how such broad steady-state distribution is maintained is unknown. Similarly, whether STEAP2 undergoes any compartment-specific modulation during intracellular trafficking has not been reported. Leveraging a newly-identified monoclonal antibody that recognizes a conformation-sensitive epitope nested in the second extracellular loop of STEAP2, we demonstrate that the epitope formation was dependent on the cholesterol content of the membrane in which STEAP2 was embedded. Monitoring the STEAP2-dependent internalization of this antibody uncovered STEAP2's rapid internalization from the cell surface and their subsequence trafficking to the Golgi region and endosome-like puncta. Acute inhibition of endocytosis also increased the detectable amount of STEAP2 at the plasma membrane. Collectively, these experiments demonstrate that an intricate balance of membrane flux between the secretory and endocytic pathways underlies the characteristic broad subcellular localization of STEAP2. By using a cell-based assay that detects the metalloreductase functions of cell surface-localizing STEAP4, STEAP2's metalloreductase activities were not detectable, suggesting that its enzymatic function is suppressed at the plasma membrane. The conformational modulation of STEAP2 by the local membrane cholesterol content can therefore serve as a potential mechanism to modulate STEAP2 function in a compartment-restricted manner, by coupling a pre-existing difference in cholesterol content among different cellular membranes to a dynamic trafficking process leading to broad subcellular distribution., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Triggering receptor expressed on myeloid cells 2 (TREM2) is an immune receptor expressed on the surface of microglia, macrophages, dendritic cells, and osteoclasts. The R47H TREM2 variant is a significant risk factor for late-onset Alzheimer's disease (AD), and the molecular basis of R47H TREM2 loss of function is an emerging area of TREM2 biology. Here, we report three high-resolution structures of the extracellular ligand-binding domains (ECDs) of R47H TREM2, apo-WT, and phosphatidylserine (PS)-bound WT TREM2 at 1.8, 2.2, and 2.2 Å, respectively. The structures reveal that Arg 47 plays a critical role in maintaining the structural features of the complementarity-determining region 2 (CDR2) loop and the putative positive ligand-interacting surface (PLIS), stabilizing conformations capable of ligand interaction. This is exemplified in the PS-bound structure, in which the CDR2 loop and PLIS drive critical interactions with PS via surfaces that are disrupted in the variant. Together with in vitro and in vivo characterization, our structural findings elucidate the molecular mechanism underlying loss of ligand binding, putative oligomerization, and functional activity of R47H TREM2. They also help unravel how decreased in vitro and in vivo stability of TREM2 contribute to loss of function in disease., (© 2018 Sudom et al.)

Approximately 20-25% of regular smokers report heavy drinking. Abstinent smokers are five times as likely to experience a smoking lapse during drinking episodes. Current efforts seek to improve treatments for this subgroup of heavy-drinking smokers. This study tested the feasibility and acceptability of addressing alcohol use in a brief, single session smoking cessation intervention (SMK+A) compared to smoking cessation counseling only (SMK); these interventions were grounded in a motivational interview framework and included personalized feedback, decisional balance, quit day setting, and tailored skills building (e.g., breathing techniques, coping with urges, dealing with social pressures) to maintain abstinence. Descriptive outcomes included reported helpfulness of intervention skills, readiness to change scores, and feasibility of participant recruitment and retention. We also assessed 7-day point prevalence of smoking cessation, and smoking and drinking reduction at 1-month follow-up. Participants ( N = 22) were community-based treatment-seeking daily smokers (≥5 cigarettes/day) who were also heavy drinkers (≥14 drinks/week for men, ≥ 7 drinks/week for women; or ≥5 drinks on one episode in past week for men, ≥4 for women). Twenty five percent of interested individuals were eligible after initial phone screen, and all randomized participants were retained through follow up. All skills demonstrated high acceptability (i.e., rated between moderately and very helpful), and a significant proportion of participants in each condition reported taking action to reduce cigarette smoking and/or alcohol use at 1-month post-quit. Three participants in each condition (27.3%) attained bioverified (CO ≤ 4 parts per million and cotinine ≤ 3 ng/mL) smoking quit at follow-up. Given the modified intervention's acceptability and flexibility, larger studies may help to elucidate this intervention's effects on readiness to change, smoking cessation, and alcohol reduction.

Chemical peels belong to a group of cutaneous resurfacing procedures that are used in the treatment of photoageing, inflammatory dermatoses, epidermal proliferations, pigmentary disorders and scarring. This review describes best current practice, highlights recent advances in chemical peel technology and discusses the recommended uses for different peel types. It also presents the results of a survey of the chemical peeling practices of 30 Australian dermatologists., (© 2017 The Australasian College of Dermatologists.)

Background: Genetic variation in the endogenous opioid system has been identified as 1 potential source of individual variability in naltrexone treatment outcomes. The majority of naltrexone pharmacogenetic studies have focused on a particular single nucleotide polymorphism (SNP) of the mu-opioid receptor gene (OPRM1; rs1799971; commonly known as the Asn40Asp SNP) in Caucasian samples with decidedly mixed results. The goal of this study was to test the pharmacogenetic effects of naltrexone on subjective response to alcohol and self-administration of alcohol in individuals of East Asian descent. We hypothesized that naltrexone, compared with placebo, would potentiate the aversive and sedative effects of alcohol and reduce alcohol self-administration to a greater extent in Asp40 carriers., Methods: Participants (N = 77; Asn40Asn, n = 29; Asn40Asp, n = 34, and Asp40Asp, n = 14) completed 2 double-blinded and counterbalanced experimental sessions: one after taking naltrexone (50 mg/d) for 5 days and one after taking matched placebo for 5 days. In each experimental session, participants received a priming dose of intravenous alcohol up to the breath alcohol concentration target of 0.06 g/dl which was immediately followed by an alcohol self-administration period (1 hour)., Results: There were no pharmacogenetic effects observed for alcohol-induced stimulation, sedation, craving for alcohol, or alcohol self-administration in the laboratory. During the self-administration period, Asp40 carriers consumed fewer drinks and had a longer latency to first drink as compared to Asn40 homozygotes., Conclusions: These findings in East Asians add to the mixed literature on naltrexone pharmacogenetics from predominantly Caucasian samples and highlight the complexity of these effects and their overall limited replicability. It is plausible that a consistent pharmacogenetic effect in tightly controlled preclinical and experimental medicine models "fades" in more complex and heterogeneous settings and samples., (Copyright © 2017 by the Research Society on Alcoholism.)

A new innovative electrode material (Fe-P800) consisting of a metal complex anchored on carbon via the utilization of iron-porphyrin conjugated microporous polymer (Fe-CMP) was prepared after pyrolyzing at 800 °C. The usage of the polymer with iron-porphyrin repeating units maximized the possible formation of Fe-N x coordination within the bulk of the sample while the thermal treatment rendered the carbon framework to form a distinct arrangement between metal, nitrogen and carbon with a high surface area of 450 m 2 g -1 . The formation of the M-N-C bond, confirmed through XPS analysis, established a direct interaction between metal and carbon material. Thus, an indisputable synergistic effect was observed leading to a high capacitance of 182 F g -1 at a current density of 1 A g -1 despite its low metal loading of ∼1%. It also exhibited a highly robust cycling stability of ∼100% capacitance retention even after 5000 cycles (10 A g -1 ). In this study, a new mechanism was proposed wherein the metal (iron) center features an electron access point via its highly reversible redox reactivity, providing a shuttle effect for charge transfer to the conductive graphitic carbon matrix.

Objective: Engagement in risk behaviors, including substance use, risky sex, and violence, tends to increase throughout adolescence into young adulthood. One motivational process that may underlie risk behaviors during adolescence is negative reinforcement. Moreover, gender and internalizing symptoms (e.g., depression and anxiety) may both convey risk for negative reinforcement-based risk taking. Along these lines, the aims of the current study were to (a) examine gender differences in negative reinforcement-based risk-taking propensity and (b) examine internalizing symptoms as a moderator of the relationship between gender and negative reinforcement-based risk-taking propensity., Method: Participants included 103 youth between the ages of 18 and 21 (50.49% female, age M(SD) = 19.41(1.06)) who were recruited from a large Mid-Atlantic university between September 2013 and November 2014. Participants completed self-report assessments of internalizing symptomatology and a computerized behavioral analog assessment of negative reinforcement-based risk-taking propensity., Results: Results indicated that, overall, female older adolescents were riskier under conditions of negative reinforcement than male older adolescents. In addition, internalizing symptoms significantly moderated the relationship between gender and negative reinforcement-based risk-taking propensity such that the relationship between gender and negative reinforcement-based risk-taking propensity was nonsignificant at high levels of internalizing symptoms, and female gender was significantly positively predictive of heightened negative reinforcement-based risk-taking propensity at low levels of internalizing symptoms., Conclusions: Thus, although female youth overall were riskier, the predictive utility of gender for negative reinforcement-based risk taking may be most relevant at low levels of internalizing symptoms. Results are discussed in terms of implications for future prevention and intervention.

Pichia pastoris is a highly successful recombinant protein expression system due to its ability to quickly generate large quantities of recombinant proteins in simple media. P. pastoris has been used to successfully generate milligram quantities of many important human membrane proteins, including G-protein coupled receptors, ion channels, and transporters, which are becoming increasingly important therapeutic targets. Despite these successes, protein expression in P. pastoris is still cumbersome due to a need to change growth media from glycerol media to methanol induction media, which minimizes inhibition of the AOX1 promoter by residual glycerol. Taking advantage of this behavior of the AOX1 promoter, we developed Buffered extra-YNB Glycerol Methanol (BYGM) auto-induction media (100 mM potassium phosphate pH 6.0, 2.68% w/v YNB, 0.4% v/v glycerol, 0.5% v/v methanol, and 8 × 10 -5 % w/v biotin) which not only simplified the protein expression process, but also optimized protein expression levels in P. pastoris. We successfully used this auto-induction method to overexpress the target in both Mut S and Mut + strains. Moreover, we show that this method can facilitate screening high-expressing clones, as well as enable parallel protein production in P. pastoris., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Aims: The current study examines the relationship between alcohol dependence severity and delay discounting neural activation., Methods: Participants (N = 17; 6 female) completed measures of alcohol use and severity and a functional magnetic resonance imaging version of a delay discounting task., Results: Alcohol dependence severity was negatively associated with activation in superior frontal gyrus during impulsive relative to delayed decisions, and positively associated with activation in paracingulate gyrus and frontal pole in delayed relative to impulsive decisions., Conclusions: These results indicate that alcohol dependence severity tracks closely with dysregulations in cognitive control and reward evaluation areas during impulsive and delayed decisions, respectively. Delay discounting may be a useful construct in capturing these cognitive dysregulations as alcohol use disorders become more severe., Short Summary: Among alcohol-dependent individuals, alcohol dependence severity is associated with overactivation of ventromedial prefrontal areas during delayed and underactivation of dorsolateral prefrontal regions during impulsive reward decisions., (© The Author 2017. Medical Council on Alcohol and Oxford University Press. All rights reserved.)

Distress tolerance is associated with a range of psychopathology and risk-taking behavior. Current research suggests that the behavioral ability to persist at goal-directed behavior when distressed may be malleable. However, little is known about the contributing factors that underlie individual differences in distress tolerance. Trait urgency, or the tendency to act impulsively in the context of acute changes in affect, may predict distress tolerance because the prepotent response to avoid or remove an aversive state may undermine persistence. To date, most research has examined the role of negative urgency, a valenced subfactor of urgency, in relation to distress tolerance. However, the broad trait of urgency may be associated with a greater change in affect that precedes the inability to tolerate distress. The current study examined whether greater changes in negative affect was indeed a mediator in the relationship between trait urgency and behavioral distress tolerance. The effects of both positive and negative urgency on affect change were examined to investigate the potential contribution of the broader urgency trait. The results suggest that a greater change in negative affect over the course of a stressor mediated the association between both subfactors of urgency and distress tolerance. These findings suggest that trait urgency, regardless of valence, may be associated with experiencing greater changes in affect that ultimately undermine the ability to tolerate distress. These findings also highlight important components of distress tolerance that could inform behavioral interventions. (PsycINFO Database Record, ((c) 2017 APA, all rights reserved).)

IL-33 is a tissue-derived cytokine that induces and amplifies eosinophilic inflammation and has emerged as a promising new drug target for asthma and allergic disease. Common variants at IL33 and IL1RL1, encoding the IL-33 receptor ST2, associate with eosinophil counts and asthma. Through whole-genome sequencing and imputation into the Icelandic population, we found a rare variant in IL33 (NM&#95;001199640:exon7:c.487-1G>C (rs146597587-C), allele frequency = 0.65%) that disrupts a canonical splice acceptor site before the last coding exon. It is also found at low frequency in European populations. rs146597587-C associates with lower eosinophil counts (β = -0.21 SD, P = 2.5×10-16, N = 103,104), and reduced risk of asthma in Europeans (OR = 0.47; 95%CI: 0.32, 0.70, P = 1.8×10-4, N cases = 6,465, N controls = 302,977). Heterozygotes have about 40% lower total IL33 mRNA expression than non-carriers and allele-specific analysis based on RNA sequencing and phased genotypes shows that only 20% of the total expression is from the mutated chromosome. In half of those transcripts the mutation causes retention of the last intron, predicted to result in a premature stop codon that leads to truncation of 66 amino acids. The truncated IL-33 has normal intracellular localization but neither binds IL-33R/ST2 nor activates ST2-expressing cells. Together these data demonstrate that rs146597587-C is a loss of function mutation and support the hypothesis that IL-33 haploinsufficiency protects against asthma.

Brain size varies greatly at all taxonomic levels. Feeding ecology, life history and sexual selection have been proposed as key components in generating contemporary diversity in brain size across vertebrates. Analyses of brain size evolution have, however, been limited to lineages where males predominantly compete for mating and females choose mates. Here, we present the first original data set of brain sizes in pipefishes and seahorses (Syngnathidae) a group in which intense female mating competition occurs in many species. After controlling for the effect of shared ancestry and overall body size, brain size was positively correlated with relative snout length. Moreover, we found that females, on average, had 4.3% heavier brains than males and that polyandrous species demonstrated more pronounced (11.7%) female-biased brain size dimorphism. Our results suggest that adaptations for feeding on mobile prey items and sexual selection in females are important factors in brain size evolution of pipefishes and seahorses. Most importantly, our study supports the idea that sexual selection plays a major role in brain size evolution, regardless of on which sex sexual selection acts stronger., (© 2016 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2016 European Society For Evolutionary Biology.)

Protein folding, topogenesis and intracellular targeting of G protein-coupled receptors (GPCRs) must be precisely coordinated to ensure correct receptor localization. To elucidate how different steps of GPCR biosynthesis work together, we investigated the process of membrane topology determination and how it relates to the acquisition of cell surface trafficking competence in human GPR34. By monitoring a fused FLAG-tag and a conformation-sensitive native epitope during the expression of GPR34 mutant panel, a tri-basic motif in the first intracellular loop was identified as the key topogenic signal that dictates the orientation of transmembrane domain-1 (TM1). Charge disruption of the motif perturbed topogenic processes and resulted in the conformational epitope loss, post-translational processing alteration, and trafficking arrest in the Golgi. The placement of a cleavable N-terminal signal sequence as a surrogate topogenic determinant overcame the effects of tri-basic motif mutations and rectified the TM1 orientation; thereby restored the conformational epitope, post-translational modifications, and cell surface trafficking altogether. Progressive N-tail truncation and site-directed mutagenesis revealed that a proline-rich segment of the N-tail and all four cysteines individually located in the four separate extracellular regions must simultaneously reside in the ER lumen to muster the conformational epitope. Oxidation of all four cysteines was necessary for the epitope formation, but the cysteine residues themselves were not required for the trafficking event. The underlying biochemical properties of the conformational epitope was therefore the key to understand mechanistic processes propelled by positive-inside rule that simultaneously regulate the topogenesis and intracellular trafficking of GPR34., (Copyright © 2016 Amgen Inc. Published by Elsevier B.V. All rights reserved.)

For decades, the literature has reported persistent treatment disparities among depressed Latinos. Fortunately, treatment development and evaluation in this underserved population has expanded in recent years. This review summarizes outcomes across 36 unique depression treatment studies that reported treatment outcomes for Latinos. Results indicated that there was significant variability in the quality of RCT and type/number of cultural adaptations. The review suggested that there might a relation between cultural adaptations with treatment outcomes; future studies are warranted to confirm this association. Cognitive Behavioral Therapy was the most evaluated treatment (CBT; n=18, 50% of all evaluations), followed by Problem Solving Therapy (PST; n=4), Interpersonal Therapy (IPT; n=4), and Behavioral Activation (BA; n=3). CBT seems to fare better when compared to usual care, but not when compared to a contact-time matched control condition or active treatment. There is growing support for PST and IPT as efficacious depression interventions among Latinos. IPT shows particularly positive results for perinatal depression. BA warrants additional examination in RCT. Although scarce, telephone and in-home counseling have shown efficacy in reducing depression and increasing retention. Promotora-assisted trials require formal assessment. Limitations and future directions of the depression psychotherapy research among Latinos are discussed., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background. Syngnathid fishes produce three kinds of sounds, named click, growl and purr. These sounds are generated by different mechanisms to give a consistent signal pattern or signature which is believed to play a role in intraspecific and interspecific communication. Commonly known sounds are produced when the fish feeds (click, purr) or is under duress (growl). While there are more acoustic studies on seahorses, pipefishes have not received much attention. Here we document the differences in feeding click signals between three species of pipefishes and relate them to cranial morphology and kinesis, or the sound-producing mechanism. Methods. The feeding clicks of two species of freshwater pipefishes, Doryichthys martensii and Doryichthys deokhathoides and one species of estuarine pipefish, Syngnathoides biaculeatus, were recorded by a hydrophone in acoustic dampened tanks. The acoustic signals were analysed using time-scale distribution (or scalogram) based on wavelet transform. A detailed time-varying analysis of the spectral contents of the localized acoustic signal was obtained by jointly interpreting the oscillogram, scalogram and power spectrum. The heads of both Doryichthys species were prepared for microtomographical scans which were analysed using a 3D imaging software. Additionally, the cranial bones of all three species were examined using a clearing and double-staining method for histological studies. Results. The sound characteristics of the feeding click of the pipefish is species-specific, appearing to be dependent on three bones: the supraoccipital, 1st postcranial plate and 2nd postcranial plate. The sounds are generated when the head of the Dorichthyes pipefishes flexes backward during the feeding strike, as the supraoccipital slides backwards, striking and pushing the 1st postcranial plate against (and striking) the 2nd postcranial plate. In the Syngnathoides pipefish, in the absence of the 1st postcranial plate, the supraoccipital rubs against the 2nd postcranial plate twice as it is pulled backward and released on the return. Cranial morphology and kinesis produce acoustic signals consistent with the bone strikes that produce sharp energy spikes (discrete or merged), or stridulations between bones that produce repeated or multimodal sinusoidal waveforms. Discussion. The variable structure of the sound-producing mechanism explains the unique acoustic signatures of the three species of pipefish. The differences in cranial bone morphology, cranial kinesis and acoustic signatures among pipefishes (and seahorses) could be attributed to independent evolution within the Syngnathidae, which warrants further investigation.

Objective: To determine whether second-trimester cervical length (CL) in women with a twin pregnancy is associated with the risk of emergency Cesarean section., Methods: This was a secondary analysis of two randomized trials conducted in 57 hospitals in The Netherlands. We assessed the univariable association between risk indicators, including second-trimester CL in quartiles, and emergency Cesarean delivery using a logistic regression model. For multivariable analysis, we assessed whether adjustment for other risk indicators altered the associations found in univariable (unadjusted) analysis. Separate analyses were performed for suspected fetal distress and failure to progress in labor as indications for Cesarean section., Results: In total, 311 women with a twin pregnancy attempted vaginal delivery after 34 weeks' gestation. Emergency Cesarean delivery was performed in 111 (36%) women, of which 67 (60%) were performed owing to arrest of labor. There was no relationship between second-trimester CL and Cesarean delivery (adjusted odds ratio (aOR): 0.97 for CL 26(th) -50(th) percentiles; 0.71 for CL 51(st)  - 75(th) percentiles; and 0.92 for CL > 75(th) percentile, using CL ≤ 25(th) percentile as reference). In multivariable analysis, the only variables associated with emergency Cesarean delivery were maternal age (aOR, 1.07 (95% CI, 1.00-1.13)), body mass index (BMI) (aOR, 3.99 (95% CI, 1.07-14.9) for BMI 20-23 kg/m(2) ; 5.04 (95% CI, 1.34-19.03) for BMI 24-28 kg/m(2) ; and 3.1 (95% CI, 0.65-14.78) for BMI > 28 kg/m(2) ) and induction of labor (aOR, 1.92 (95% CI, 1.05-3.5))., Conclusion: In nulliparous women with a twin pregnancy, second-trimester CL is not associated with risk of emergency Cesarean delivery., (Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: Cervical length (CL) is associated with the risk of preterm birth (PTB) in multiple pregnancies. However, the position of CL within the pathophysiological pathway of PTB is unclear, and it is unknown which factors are predictive for CL. This study aims to investigate whether in twin pregnancies baseline maternal and obstetrical characteristics are potential indicators for CL, to improve insight in the pathophysiological pathway of PTB., Study Design: Secondary analysis of data on twin pregnancies and CL measurement between 16 and 22 weeks. A set of 10 potential indicators, known to be associated with an increased risk of PTB and/or which have a plausible mechanism resulting in a change of CL were selected. We used multivariable linear regression with backward selection to identify independent indicators for CL., Results: A total of 1,447 women with twin pregnancies were included. Mean CL was 43.7 (±8.9) mm. In multivariable analysis, age (0.27 mm/y; 95% confidence interval [CI] 0.16 to 0.39), use of assisted reproductive technologies (ART) (-1.42 mm, 95% CI -2.6 to -0.25), and having delivered at term in a previous pregnancy (1.32 mm, 95% CI 0.25 to 2.39) were significantly associated with CL., Conclusion: This study shows that in twin pregnancies, age, use of ART and having delivered term in a previous pregnancy has an association with CL., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Drag area (Ad ) is a primary factor determining aerodynamic resistance during level cycling and is therefore a key determinant of level time trial performance. However, Ad has traditionally been difficult to measure. Our purpose was to determine the value of adding field-measured Ad as a correlate of level cycling time trial performance. In the field, 19 male cyclists performed a level (22.1 km) time trial. Separately, field-determined Ad and rolling resistance were calculated for subjects along with projected frontal area assessed directly (AP ) and indirectly (Est AP ). Also, a graded exercise test was performed to determine [Formula: see text] peak, lactate threshold (LT), and economy. [Formula: see text] peak ([Formula: see text]) and power at LT were significantly correlated to power measured during the time trial (r = 0.83 and 0.69, respectively) but were not significantly correlated to performance time (r = - 0.42 and -0.45). The correlation with performance time improved significantly (p < 0.05) when these variables were normalized to Ad . Of note, Ad alone was better correlated to performance time (r = 0.85, p < 0.001) than any combination of non-normalized physiological measure. The best correlate with performance time was field-measured power output during the time trial normalized to Ad (r = - 0.92). AP only accounted for 54% of the variability in Ad . Accordingly, the correlation to performance time was significantly lower using power normalized to AP (r = - 0.75) or Est AP (r = - 0.71). In conclusion, unless normalized to Ad , level time trial performance in the field was not highly correlated to common laboratory measures. Furthermore, our field-measured Ad is easy to determine and was the single best predictor of level time trial performance.

Acoustic signals of the tiger-tail seahorse (Hippocampus comes) during feeding were studied using wavelet transform analysis. The seahorse "click" appears to be a compounded sound, comprising three acoustic components that likely come from two sound producing mechanisms. The click sound begins with a low-frequency precursor signal, followed by a sudden high-frequency spike that decays quickly, and a final, low-frequency sinusoidal component. The first two components can, respectively, be traced to the sliding movement and forceful knock between the supraorbital bone and coronet bone of the cranium, while the third one (purr) although appearing to be initiated here is produced elsewhere. The seahorse also produces a growling sound when under duress. Growling is accompanied by the highest recorded vibration at the cheek indicating another sound producing mechanism here. The purr has the same low frequency as the growl; both are likely produced by the same structural mechanism. However, growl and purr are triggered and produced under different conditions, suggesting that such "vocalization" may have significance in communication between seahorses.

Life-history variables for three incidentally captured species of seahorse (Kellogg's seahorse Hippocampus kelloggi, the hedgehog seahorse Hippocampus spinosissimus and the three-spot seahorse Hippocampus trimaculatus) were established using specimens obtained from 33 fisheries landing sites in Peninsular Malaysia. When samples were pooled by species across the peninsula, sex ratios were not significantly different from unity, and height and mass relationships were significant for all species. For two of these species, height at physical maturity (HM ) was smaller than the height at which reproductive activity (HR ) commenced: H. spinosissimus (HM = 99·6 mm, HR = 123·2 mm) and H. trimaculatus (HM = 90·5 mm, HR = 121·8 mm). For H. kelloggi, HM could not be estimated as all individuals were physically mature, while HR = 167·4 mm. It appears that all three Hippocampus spp. were, on average, caught before reproducing; height at 50% capture (HC ) was ≥HM but ≤HR . The results from this study probe the effectiveness of assessment techniques for data-poor fisheries that rely heavily on estimates of length at maturity, especially if maturity is poorly defined. Findings also question the sustainability of H. trimaculatus catches in the south-west region of Peninsular Malaysia, where landed specimens had a notably smaller mean height (86·2 mm) and markedly skewed sex ratio (6% males) compared with samples from the south-east and north-west of the peninsula., (© 2014 The Fisheries Society of the British Isles.)

Crystalline bodies (CBs) can develop in the endoplasmic reticulum (ER) of antibody-producing cells. Although this phenotype is often reported in association with plasma cell dyscrasias and other hematological disorders, the details of CB biogenesis and CB's roles in pathophysiology remain poorly understood. Using an imaging-based screening method, we identified a secretion-competent human IgG2/λ clone that develops spindle-shaped intracellular crystals in transiently-transfected HEK293 cells upon Brefeldin A treatment. When stably overexpressed from CHO cells, the IgG2/λ clone spontaneously produced spindle-shaped CBs in the ER. Some CBs were released to the extracellular space while remaining enclosed by the membranes of secretory pathway origin. Structural modeling on the variable-region did not uncover prominent surface characteristics such as charge clusters. In contrast, alterations to the constant domain-encoded properties revealed their modulatory roles in CB-inducing propensities and CB morphology. For example, deletion of the entire Fc domain changed the morphology of CBs into thin filaments. Elimination of an N-linked glycan by a N297A mutation promoted Russell body biogenesis accompanied by marked reduction in IgG secretion. Isotype class switching from the original IgG2 to IgG1 and IgG4 changed the crystal morphology from spindle-shaped to long needle and acicular shaped, respectively. The IgG3 version, in contrast, suppressed the CB formation. Either the HC or LC alone or the Fc-domain alone did not trigger CB biogenesis. An IgG's in vivo crystal morphology and crystallization propensity can thus be modulated by the properties genetically and biochemically encoded in the HC constant region., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Objective: To develop a multivariable prognostic model for the risk of preterm delivery in women with multiple pregnancy that includes cervical length measurement at 16 to 21 weeks' gestation and other variables., Methods: We used data from a previous randomized trial. We assessed the association between maternal and pregnancy characteristics including cervical length measurement at 16 to 21 weeks' gestation and time to delivery using multivariable Cox regression modelling. Performance of the final model was assessed for the outcomes of preterm and very preterm delivery using calibration and discrimination measures., Results: We studied 507 women, of whom 270 (53%) delivered < 37 weeks (preterm) and 66 (13%) < 32 weeks (very preterm). Women with cervical length < 30 mm delivered more often preterm (hazard ratio 1.9; 95% CI 0.7 to 4.8). Other independently contributing predictors were previous preterm delivery, monochorionicity, smoking, educational level, and triplet pregnancy. Prediction models for preterm and very preterm delivery had a c-index of 0.68 (95% CI 0.63 to 0.72) and 0.68 (95% CI 0.62 to 0.75), respectively, and showed good calibration., Conclusion: In women with a multiple pregnancy, the risk of preterm delivery can be assessed with a multivariable model incorporating cervical length and other predictors.

Part two of this review series evaluates the use of lasers and laser-like devices in dermatology based on published evidence and the collective experience of the senior authors. Dermatologists can laser-treat a wide range of dermatoses, including vascular, pigmentary, textural, benign proliferative and premalignant conditions. Some of these conditions include vascular malformation, haemangioma, facial telangiectases, café-au-lait macules, naevi of Ota, lentigines, acne scarring, rhytides, rhinophyma and miscellaneous skin lesions. Photodynamic therapy with lasers and intense pulsed light is addressed, with particular reference to actinic keratosis and actinic cheilitis. A treatment algorithm for acne scarring based on scar morphology and severity is comprehensively outlined. Following from part one, the various devices are matched to the corresponding dermatological conditions with representative pictorial case vignettes illustrating likely clinical outcomes as well as limitations and potential complications of the various laser and light therapies., (© 2013 The Australasian College of Dermatologists.)

The underlying reasons for why some mAb (monoclonal antibody) clones are much more inclined to induce a Russell body (RB) phenotype during immunoglobulin biosynthesis remain elusive. Although RBs are morphologically understood as enlarged globular aggregates of immunoglobulins deposited in the endoplasmic reticulum (ER), little is known about the properties of the RB-inducing mAb clones as secretory cargo and their physical behaviors in the extracellular space. To elucidate how RB-inducing propensities, secretion outputs, and the intrinsic physicochemical properties of individual mAb clones are interrelated, we used HEK293 cells to study the biosynthesis of 5 human IgG mAbs for which prominent solution behavior problems were known a priori. All 5 model mAbs with inherently high condensation propensities induced RB phenotypes both at steady state and under ER-to-Golgi transport block, and resulted in low secretion titer. By contrast, one reference mAb that readily crystallized at neutral pH in vitro produced rod-shaped crystalline bodies in the ER without inducing RBs. Another reference mAb without notable solution behavior issues did not induce RBs and was secreted abundantly. Intrinsic physicochemical properties of individual IgG clones thus directly affected the biosynthetic steps in the ER, and thereby produced distinctive cellular phenotypes and influenced IgG secretion output. The findings implicated that RB formation represents a phase separation event or a loss of colloidal stability in the secretory pathway organelles. The process of RB induction allows the cell to preemptively reduce the extracellular concentration of potentially pathogenic, highly aggregation-prone IgG clones by selectively storing them in the ER.

Central nervous system spread from prostate cancer is typically associated with raised prostate specific antigen (PSA) levels. The authors describe a unique case of a "collision tumor" of a prostatic metastasis to the pituitary, juxtaposed to a suprasellar meningioma, with normal PSA levels. This case also emphasizes the need to consider prostatic metastasis in the differential diagnosis of a pituitary mass in patients with a known prostatic cancer, despite the normal PSA levels., (Georg Thieme Verlag KG Stuttgart · New York.)

Objective: Increasingly, maternal administration of 17-α-hydroxyprogesterone caproate (17-OHPC) is utilized to prevent preterm birth, but the fetal safety of 17-OHPC is still a matter of concern. This study aimed to assess whether exposure to 17-OHPC during the second and third trimesters of pregnancy affects fetal biometry in twin gestations., Methods: This study included a subset of women with a twin pregnancy who had been previously included in a randomized clinical trial comparing the effectiveness of 17-OHPC and placebo on neonatal outcomes and preterm birth rates in multiple pregnancy. In the present study, the individual growth patterns of femur length, head circumference and abdominal circumference were compared between fetuses of women who had been randomized to receive weekly injections of either 17-OHPC (n = 52) or placebo (n = 58) at between 16-20 and 36 weeks' gestation., Results: The three biometric variables assessed developed similarly in fetuses in both the group exposed to 17-OHPC and the placebo group during the second half of pregnancy. Birth weight adjusted for parity and fetal sex was also comparable between groups., Conclusion: The use of 17-OHPC has no adverse effects on fetal biometry and birth weight in twins., (Copyright © 2013 ISUOG. Published by John Wiley & Sons Ltd.)

Lasers have been used in dermatology for nearly 50 years. Through their selective targeting of skin chromophores they have become the preferred treatment for many skin conditions, including vascular malformations, photorejuvenation and acne scars. The technology and design of lasers continue to evolve, allowing greater control of laser parameters and resulting in increased safety and efficacy for patients. Innovations have allowed the range of conditions and the skin types amenable to treatment, in both general and cosmetic dermatology, to expand over the last decade. Integrated skin cooling and laser beam fractionation, for example, have improved safety, patient tolerance and decreased downtime. Furthermore, the availability and affordability of quality devices continues to increase, allowing clinicians not only to access laser therapies more readily but also to develop their personal experience in this field. As a result, most Australian dermatologists now have access to laser therapies, either in their own practice or within referable proximity, and practical knowledge of these technologies is increasingly required and expected by patients. Non-laser energy devices utilising intense pulsed light, plasma, radiofrequency, ultrasound and cryolipolysis contribute to the modern laser practitioners' armamentarium and will also be discussed., (© 2013 The Authors. Australasian Journal of Dermatology © 2013 The Australasian College of Dermatologists.)

The growth and dependence of Prostate Cancer (PCa) on androgen stimulation led to the use of castration to reduce circulating levels of androgens and anti-androgens to directly target the androgen receptor (AR) ligand-binding domain (LBD). However, castration-resistant prostate cancer (CRPC) resistant to anti-androgens invariably develops and can be associated with AR genomic aberrations (mutations, amplification) and/or an increase in AR mRNA expression. Efforts to more effectively target the AR in CRPC led to the rational design of CYP17A1 inhibitors and more potent antiandrogens. The front-runner 2nd generation rationally-designed therapeutics targeting the AR, abiraterone and enzalutamide have been shown to improve survival and clinical outcome for CRPC patients. Several other CYP17A1 inhibitors and anti-androgens are in clinical and preclinical development. However, patients ultimately progress and current evidence suggests that this can occur through reactivation of AR signaling. Several ongoing programs aim to develop LBD independent therapeutic strategies that for example target the N terminus domain (NTD) of the AR or chaperone proteins. Rationally-designed approaches combining different strategies for targeting the AR or associated pathways also warrant clinical evaluation.

Objective. The aim of this study was to assess whether cervical length measurement (CL) could predict preterm birth (PTB) in symptomatic women with a twin pregnancy. Methods. We searched MEDLINE and EMBASE to identify studies investigating the accuracy of CL measurement in predicting PTB in symptomatic women with a twin pregnancy. We extracted data to construct two-by-two tables and used bivariate meta-analysis to generate point estimates of sensitivity and specificity. Results. Five studies (N = 226) were included. Variation in definition of PTB and cut-off points for CL was strong. One study investigated delivery within seven days, demonstrating a sensitivity of 1.0 (95% CI: 0.83-1.0) and a specificity of 0.31 (95% CI 0.2-0.43) for a CL cutoff at 25 mm. Three studies reported on predicting PTB < 37 weeks at a CL cutoff of 30 mm, with sROC point estimates of 0.76 (95% CI: 0.66 to 0.84) and 0.37 (95% CI: 0.21 to 0.56) for sensitivity and specificity, respectively. For preterm birth <34 weeks, no pooled estimates could be estimated since only 2 studies with large heterogeneity were identified. Conclusions. There is limited evidence on the accuracy of cervical length measurement testing the prediction of preterm birth in symptomatic women with a twin pregnancy, especially on the most important outcome, that is, delivery within 7 days.

Objectives: Previous studies on singleton pregnancies have indicated that progestogens may reduce the rate of cervical shortening during pregnancy. The aim of this study was to investigate whether treatment with 17-alpha hydroxyprogesterone caproate (17-OHPC) has an effect on cervical shortening in twin pregnancies., Methods: This was a secondary analysis of patients who had participated in a multicenter randomized clinical trial on the effectiveness of 17-OHPC in preventing preterm birth in multiple pregnancies (the AMPHIA-trial). We included all trial participants with a twin gestation who had undergone repeat cervical length measurements during pregnancy. We performed a separate analysis of women with repeat measurements in centers where this was standard protocol for multiple pregnancies. The rate of cervical shortening for both the 17-OHPC group and the placebo group was analyzed using a linear mixed model., Results: Of the 671 patients who participated in the trial, 282 (42%) had a twin pregnancy and underwent two or more cervical length measurements. Of these women, 140 were monitored in centers where repeat measurements were standard protocol. We observed an overall reduction of cervical length from 44.3 mm at 14-18 weeks to 30.0 mm at 30-34 weeks' gestation. In the 17-OHPC group, cervical length decreased by 1.04 mm each gestational week, while this was 1.11 mm per week for the placebo group (P = 0.6). For the overall group, each 10% decrease in cervical length led to an increase in the risk of preterm birth (hazard ratio, 1.14; 95% CI, 1.08-1.21)., Conclusion: In women with a twin pregnancy, there is progressive shortening of the cervix during pregnancy, regardless of 17-OHPC use., (Copyright © 2012 ISUOG. Published by John Wiley & Sons, Ltd.)

Prostate cancer progression can be associated with androgen receptor (AR) mutations acquired following treatment with castration and/or an antiandrogen. Abiraterone, a rationally designed inhibitor of CYP17A1 recently approved for the treatment of docetaxel-treated castration-resistant prostate cancer (CRPC), is often effective, but requires coadministration with glucocorticoids to curtail side effects. Here, we hypothesized that progressive disease on abiraterone may occur secondary to glucocorticoid-induced activation of mutated AR. We found that prednisolone plasma levels in patients with CRPC were sufficiently high to activate mutant AR. Mineralocorticoid receptor antagonists, such as spironolactone and eplerenone that are used to treat side effects related to mineralocorticoid excess, can also bind to and activate signaling through wild-type or mutant AR. Abiraterone inhibited in vitro proliferation and AR-regulated gene expression of AR-positive prostate cancer cells, which could be explained by AR antagonism in addition to inhibition of steroidogenesis. In fact, activation of mutant AR by eplerenone was inhibited by MDV3100, bicalutamide, or greater concentrations of abiraterone. Therefore, an increase in abiraterone exposure could reverse resistance secondary to activation of AR by residual ligands or coadministered drugs. Together, our findings provide a strong rationale for clinical evaluation of combined CYP17A1 inhibition and AR antagonism., (©2012 AACR)

Background: Preterm birth is the principal factor contributing to adverse outcomes in multiple pregnancies. Randomized controlled trials of progestogens to prevent preterm birth in twin pregnancies have shown no clear benefits. However, individual studies have not had sufficient power to evaluate potential benefits in women at particular high risk of early delivery (for example, women with a previous preterm birth or short cervix) or to determine adverse effects for rare outcomes such as intrauterine death., Methods/design: We propose an individual participant data meta-analysis of high quality randomized, double-blind, placebo-controlled trials of progestogen treatment in women with a twin pregnancy. The primary outcome will be adverse perinatal outcome (a composite measure of perinatal mortality and significant neonatal morbidity). Missing data will be imputed within each original study, before data of the individual studies are pooled. The effects of 17-hydroxyprogesterone caproate or vaginal progesterone treatment in women with twin pregnancies will be estimated by means of a random effects log-binomial model. Analyses will be adjusted for variables used in stratified randomization as appropriate. Pre-specified subgroup analysis will be performed to explore the effect of progestogen treatment in high-risk groups., Discussion: Combining individual patient data from different randomized trials has potential to provide valuable, clinically useful information regarding the benefits and potential harms of progestogens in women with twin pregnancy overall and in relevant subgroups.

The introduction of tyrosine kinase inhibitors (TKIs), starting with imatinib and followed by second and third generation TKIs, has significantly changed the clinical management of patients with chronic myeloid leukemia (CML). Despite their unprecedented clinical success, a proportion of patients fail to achieve complete cytogenetic remission by 12 months of treatment (primary resistance) while others experience progressive resistance after an initial response (secondary resistance). BCR-ABL1 kinase domain (KD) mutations have been detected in a proportion of patients at the time of treatment failure, and therefore their identification and monitoring plays an important role in therapeutic decisions particularly when switching TKIs. When monitoring KD mutations in a clinical laboratory, the choice of method should take into account turnaround time, cost, sensitivity, specificity, and ability to accurately quantify the size of the mutant clone. In this article, we describe in a "manual" style the methods most widely used in our laboratory to monitor KD mutations in patients with CML including direct sequencing, D-HPLC, and pyrosequencing. Advantages, disadvantages, interpretation of results, and their clinical applications are reviewed for each method., (Copyright © 2011 Wiley Periodicals, Inc.)

Objectives: To review the literature on cervical length as a predictor of preterm birth in asymptomatic women with a multiple pregnancy., Methods: We searched MEDLINE, Embase and reference lists of included articles to identify all studies that reported on the accuracy of cervical length for predicting preterm birth in asymptomatic women with a multiple pregnancy. We scored study characteristics and study quality, and extracted data in order to construct two-by-two tables cross-classifying cervical length and preterm delivery. Meta-analysis using a bivariate model was performed. Summary receiver-operating characteristics (ROC) curves were generated for various test characteristics and outcome definitions., Results: We found 21 studies reporting on 2757 women. There was a large variation in gestational age at measurement, cut-off point for cervical length and definition of preterm birth. The summary ROC curve indicated a good predictive capacity of short cervical length for preterm birth. Summary estimates of sensitivity and specificity for preterm birth before 34 weeks' gestation were 78% and 66%, respectively, for 35 mm, 41% and 87% for 30 mm, 36% and 94% for 25 mm and 30% and 94% for 20 mm., Conclusions: In women with a multiple pregnancy, second-trimester cervical length is a strong predictor of preterm birth. In the absence of effective preventive strategies, there is currently no place in clinical practice for cervical length measurement in this population. However, future studies should evaluate preventive interventions in women with multiple pregnancies and a short cervix, and cervical length should be measured in any trial studying preventive strategies in multiple pregnancies., (Copyright © 2011 ISUOG. Published by John Wiley & Sons, Ltd.)