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Global warming caused by increased greenhouse gas (GHG) emissions has a direct impact on human health. Gastrointestinal (GI) endoscopy contributes significantly to GHG emissions due to energy consumption, reprocessing of endoscopes and accessories, production of equipment, safe disposal of biohazardous waste, and travel by patients. Moreover, GHGs are also generated in histopathology through tissue processing and the production of biopsy specimen bottles. The reduction in unnecessary surveillance endoscopies and biopsies is a practical approach to decrease GHG emissions without affecting disease outcomes. This narrative review explores the role of precision medicine in GI endoscopy, such as image‐enhanced endoscopy and artificial intelligence, with a focus on decreasing unnecessary endoscopic procedures and biopsies in the surveillance and diagnosis of premalignant lesions in the esophagus, stomach, and colon. This review offers strategies to minimize unnecessary endoscopic procedures and biopsies, decrease GHG emissions, and maintain high‐quality patient care, thereby contributing to sustainable healthcare practices. [ABSTRACT FROM AUTHOR]

Summary: Background: One‐week triple therapy with vonoprazan is endorsed by Japanese guidelines as an alternative to proton pump inhibitor (PPI)‐based triple therapy for first‐line Helicobacter pylori eradication. This contrasts with Western guidelines recommending 2‐week PPI‐based triple therapy. Aim: To verify the non‐inferiority of 1‐week vonoprazan‐based triple therapy versus 2‐week PPI‐based triple therapy as first‐line H. pylori eradication in a multiracial Asian cohort. Methods: Randomised controlled trial of treatment‐naïve patients with H. pylori infection assigned 1:1 to either 7 days amoxicillin 1 g + clarithromycin 500 mg + vonoprazan 20 mg twice per day or 14 days amoxicillin 1 g + clarithromycin 500 mg + omeprazole OR esomeprazole OR rabeprazole 20 mg twice/day. Subjects were randomly assigned to each PPI 1:1:1 Demographics, H. pylori resistance, CYP 2C19 genotype, eradication success and safety profiles were compared between groups. Results: Between June 2019 and June 2021, 252 of 1097 subjects screened were randomised. 244 (age [SD] 51.7 [14.6]) received vonoprazan‐ (n = 119) or PPI‐based (n = 125) triple therapy. Eradication rates by intention‐to‐treat analysis were 87.4% (vonoprazan‐based triple therapy) versus 88.0% (PPI‐based triple therapy. By per protocol analysis: 96.3% (vonoprazan‐based triple therapy) versus 94.0% (PPI‐based triple therapy). Clarithromycin resistance predicted treatment failure on multivariate analysis: RR 11.4; 95% CI [1.4–96.3], p = 0.025. No significant differences in CYP 2C19 genotypes or adverse events occurred between groups. Conclusion: One‐week vonoprazan‐based triple therapy achieved comparable efficacy to 2‐week PPI‐based triple therapy and was well tolerated. [ABSTRACT FROM AUTHOR]

Background and Aim: Artificial intelligence has been extensively studied to assist clinicians in polyp detection, but such systems usually require expansive processing power, making them prohibitively expensive and hindering wide adaption. The current study used a fast object detection algorithm, known as the YOLOv3 algorithm, to achieve real‐time polyp detection on a laptop. In addition, we evaluated and classified the causes of false detections to further improve accuracy. Methods: The YOLOv3 algorithm was trained and validated with 6038 and 2571 polyp images, respectively. Videos from live colonoscopies in a tertiary center and those obtained from public databases were used for the training and validation sets. The algorithm was tested on 10 unseen videos from the CVC‐Video ClinicDB dataset. Only bounding boxes with an intersection over union area of > 0.3 were considered positive predictions. Results: Polyp detection rate in our study was 100%, with the algorithm able to detect every polyp in each video. Sensitivity, specificity, and F1 score were 74.1%, 85.1%, and 83.3, respectively. The algorithm achieved a speed of 61.2 frames per second (fps) on a desktop RTX2070 GPU and 27.2 fps on a laptop GTX2060 GPU. Nearly a quarter of false negatives happened when the polyps were at the corner of an image. Image blurriness accounted for approximately 3% and 9% of false positive and false negative detections, respectively. Conclusion: The YOLOv3 algorithm can achieve real‐time poly detection with high accuracy and speed on a desktop GPU, making it low cost and accessible to most endoscopy centers worldwide. [ABSTRACT FROM AUTHOR]

Background and Aim: Gastrointestinal (GI) lesions may have subtle morphological changes. Linked color imaging (LCI) combines narrow‐band wavelength light and white light imaging (WLI) in appropriate balance to enhance lesion detection. We compared the detection rates of upper GI lesions using LCI and WLI. Method: Patients were randomized in a 1:1 ratio to receive tandem gastroscopy with WLI inspection followed by LCI, or vice versa. Endoscopic examination was performed using the EG‐L590ZW gastroscope and the LASEREO endoscope system (Fujifilm Co., Tokyo, Japan). Histology was reported by a specialist GI pathologist blinded to the technique of lesion detection and was used as the gold standard for diagnosis. Results: Ninety patients (mean age 66.8 years, 51.5% male patients) were randomized to either LCI examination first followed by WLI (LCI‐WLI), or vice versa (WLI‐LCI). An 18.9% of gastroscopies in the study were for surveillance of previously known gastric cancer precursors. Ten patients (11.1%) had a history of Helicobacter pylori infection. There was no significant difference in the time taken for examination under LCI (311 ± 96 s) and WLI (342 ± 86 s) (P = 0.700). LCI detection rates were higher than WLI detection rates for gastric cancer precursors such as atrophic gastritis (2.19% vs 0.55%) (P < 0.01) and intestinal metaplasia (19.73% vs 7.67%) (P < 0.01). Both sensitivity (82.74% vs 50.96%) and specificity (98.71% vs 96.10%) of LCI were higher than WLI for detection of upper GI lesions. Conclusions: Linked color imaging had better detection rates, sensitivity, and specificity for detection of upper GI lesions compared with WLI. [ABSTRACT FROM AUTHOR]

We introduce the tensor auto‐regressive (TAR) model for modeling time series data, which is found to be robust to model misspecification, seasonality, and nonlinear trends. We develop a parameter estimation algorithm for the proposed model by using the 𝑡‐product, which allows us to model a three‐dimensional block of parameters. We use the fast Fourier transform, which allows for efficient and parallelizable computation. We use a combination of simulated data and an empirical application to: (i) validate the model, including seasonal and geometric trends, model misspecification analysis, and bootstrapping to compute standard errors; (ii) present model selection results; and (iii) demonstrate the performance of the proposed model against benchmarking and competitive forecasting methods. Our results indicate that our model performs well against comparable methods and is robust and computationally efficient. [ABSTRACT FROM AUTHOR]

Background: There is converging evidence that mental disorders are more optimally conceptualized in a hierarchical framework (i.e., the Hierarchical Taxonomy of Psychopathology, HiTOP) that transcends the categorical boundaries of the Diagnostic and Statistical Manual of Mental Disorders (DSM). However, the majority of this evidence comes from studies that draw upon predominantly European American or Caucasian populations. Whether a hierarchical conceptualization of mental disorders generalizes across racial‐ethnic groups, including for African American (AA) populations, is unclear. Methods: We tested multidimensional and bifactor models of 15 DSM diagnoses and psychiatric traits in two groups, including AA (n = 3,088) and European American (EA; n = 5,147) youths aged 8–21 from the Philadelphia Neurodevelopmental Cohort (PNC). We also conducted multigroup confirmatory factor analyses to test for factorial invariance between the best fitting AA and EA multidimensional and bifactor models. Results: In the multidimensional model tests, a three‐factor model, specifying internalizing, externalizing, and thought dimensions, emerged as the best fitting model for AAs and EAs. In the bifactor model tests, a three‐factor model (i.e., internalizing, externalizing, and thought dimensions) that also specified a general factor emerged as the optimal for both AAs and EAs. The general factor accounted for a significant proportion of the covariation between the secondary factors and the individual disorders and traits. Furthermore, both models were factorially invariant, indicating no significant difference in the factor structure of mental disorders between AAs and EAs in PNC. Conclusions: Results suggest that the hierarchical factor structure of mental disorders may be racial‐ethnically robust. This finding has implications for etiological and epidemiological studies focused on racial‐ethnic subgroup comparisons, particularly with respect to identifying similarities and differences in prevalence rates or sociodemographic risk factors for mental disorders. [ABSTRACT FROM AUTHOR]

However, there are uncertainties regarding how to optimize EUS-TA to ensure sufficient tissue samples for CGP as different analytical platforms require different amount of tissue samples for successful CGP. Thus, endoscopic ultrasound-guided tissue-acquisition (EUS-TA) not only plays a central role in diagnosis but is also essential for providing adequate tissue samples for CGP in the absence of surgical resected specimens. Comprehensive genomic profiling (CGP) of tumor tissues by next-generation sequencing (NGS) can identify significant mutated genes that may lead to genome-matched therapy and better prognosis. [Extracted from the article]

Interestingly, a separate selection of 62 matched pairs of patients also showed that the median dissection time was faster in the U-ESD group compared to patients undergoing C-ESD [10.9 (7.5-16.5) mm SP 2 sp /min I vs i 6.9 (4.7-11.9) mm SP 2 sp /min; I P i < 0.001]. A key advantage of underwater endoscopic mucosal resection is the rapid dissipation of thermal energy during the application of electrocautery for resection of polyps. Underwater endoscopic mucosal resection has gained attention in the literature[1] for its efficacy and ease of use in the resection of intermediate[2] and large[3] colorectal polyps. [Extracted from the article]

Background: Children with ADHD frequently engage in higher rates of externalizing behaviors in adulthood relative to children without. However, externalizing behaviors vary across development. Little is known about how this risk unfolds across development. Phenotypic and polygenic models of childhood ADHD were used to predict individual differences in adult externalizing trajectories. Supportive parenting, school connectedness, and peer closeness were then examined as causal mechanisms. Methods: Data were from the National Longitudinal Study of Adolescent to Adult Health (N = 7,674). Externalizing behavior was measured using data from age 18 to 32 and modeled using latent class growth analysis. Child ADHD was measured using retrospective self‐report (phenotypic model) and genome‐wide polygenic risk scores (polygenic model). Multiple mediation models examined the direct and indirect effects of the phenotypic and polygenic models (separately) on externalizing trajectories through the effects of adolescent supportive parenting, school connectedness, and peer closeness. Results: Phenotypic and polygenic models of ADHD were associated with being in the High Decreasing (3.2% of sample) and Moderate (16.1%) adult externalizing trajectories, but not the severe Low Increasing trajectory (2.6%), relative to the Normal trajectory (78.2%). Associations between both models of ADHD on the High Decreasing and Moderate trajectories were partially mediated through the effects of school connectedness, but not supportive parenting or peer closeness. Conclusions: Findings shed light on how childhood ADHD affects downstream psychosocial processes that then predict specific externalizing outcomes in adulthood. They also reinforce the importance of fostering a strong school environment for adolescents with (and without) ADHD, as this context plays a critical role in shaping the development of externalizing behaviors in adulthood. [ABSTRACT FROM AUTHOR]

Existing methodologies to produce human neural stem cells and neurons from embryonic stem cells frequently involve multistep processes and the use of complex and expensive media components, cytokines or small molecules. Here, we report a simple technique to generate human neuroepithelial progenitors and neurons by periodic mechanical dissection and adherent‐cell depletion on regular cell‐culture grade plastic surfaces. This neural induction technique does not employ growth factors, small molecules or peptide inhibitors, apart from those present in serum‐free supplements. Suggestive of their central nervous system origin, we found that neural progenitors formed by this technique expressed radial glia markers, and, when differentiated, expressed TUBB3, RBFOX3 (NeuN) and serotonin, but not markers for peripheral neurons. With these data, we postulate that incorporation of periodic mechanical stimuli and plastic surface‐mediated cell selection could improve and streamline existing human neuron production protocols. [ABSTRACT FROM AUTHOR]

Ceftaroline, the active form of the prodrug ceftaroline fosamil, is approved for use in adults with community-acquired bacterial pneumonia (CABP) or acute bacterial skin and skin structure infections (ABSSSI) in the United States and for similar indications in Europe. Pharmacokinetic (PK) data from 5 pediatric (birth to <18 years) studies of ceftaroline fosamil were combined with PK data from adults to update a population PK model for ceftaroline and ceftaroline fosamil. This model, based on a data set including 305 children, was used to conduct simulations to estimate ceftaroline exposures and percentage of time that free drug concentrations were above the minimum inhibitory concentration (% fT>MIC) for pediatric dose regimens. With dose regimens of 8 mg/kg every 8 hours (q8h) in children aged 2 months to <2 years and 12 mg/kg (up to a maximum of 400 mg) q8h in children aged 2 years to <18 years or 600 mg q12h in children aged 12 to <18 years, >90% of children were predicted to achieve a target of 36% fT>MIC at an MIC of 2 mg/L, and >97% were predicted to achieve 44% fT>MIC at an MIC of 1 mg/L. Thus, high PK/pharmacodynamic target attainment would be maintained in children for targets associated with 1-log kill of Staphylococcus aureus and Streptococcus pneumoniae. The predicted ceftaroline exposures for these dose regimens were similar to those in adults given 600 mg q12h ceftaroline fosamil. This work contributed to the approval of dose regimens for children aged 2 months to <18 years by the FDA and EMA, which are presented. [ABSTRACT FROM AUTHOR]

Excessive power supply noise (PSN) such as IR drop can cause yield loss when testing very large scale integration chips. However, simulation of circuit timing with PSN is not an easy task. In this study, the authors predict circuit timing for all test patterns using three machine learning techniques, neural network (NN), support vector regression (SVR), and least‐square boosting (LSBoost). To reduce the huge dimension of raw data, they propose four feature extractions: input/output transition (IOT), flip‐flop transition in window (FFTW), switching activity in window (SAW), and terminal FF transition of long paths (PATH). SAW and FFTW are physical‐aware features while PATH is a timing‐aware feature. Their experimental results on leon3mp benchmark circuit (638 K gates, 2 K test patterns) show that, compared with the simple IOT method, SAW effectively reduced the dimension by up to 472 times, without significant impact on prediction accuracy [correlation coefficient = 0.79]. Their results show that NN has best prediction accuracy and SVR has the least under‐prediction. LSBoost uses the least memory. The proposed method is more than six orders of magnitude faster than traditional circuit simulation tools. [ABSTRACT FROM AUTHOR]

Background Heavy episodic drinking is developmentally normative among adolescents and young adults, but is linked to adverse consequences in later life, such as drug and alcohol dependence. Genetic and peer influences are robust predictors of heavy episodic drinking in youth, but little is known about the interplay between polygenic risk and peer influences as they impact developmental patterns of heavy episodic drinking. Methods Data were from a multisite prospective study of alcohol use among adolescents and young adults with genome-wide association data ( n = 412). Generalized linear mixed models were used to characterize the initial status and slopes of heavy episodic drinking between age 15 and 28. Polygenic risk scores (PRS) were derived from a separate genome-wide association study for alcohol dependence and examined for their interaction with substance use among the adolescents' closest friends in predicting the initial status and slopes of heavy episodic drinking. Results Close friend substance use was a robust predictor of adolescent heavy episodic drinking, even after controlling for parental knowledge and peer substance use in the school. PRS were predictive of the initial status and early patterns of heavy episodic drinking in males, but not in females. No interaction was detected between PRS and close friend substance use for heavy episodic drinking trajectories in either males or females. Conclusions Although substance use among close friends and genetic influences play an important role in predicting heavy episodic drinking trajectories, particularly during the late adolescent to early adult years, we found no evidence of interaction between these influences after controlling for other social processes, such as parental knowledge and broader substance use among other peers outside of close friends. The use of longitudinal models and accounting for multiple social influences may be crucial for future studies focused on uncovering gene-environment interplay. Clinical implications are also discussed. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Needle knife precut sphincterotomy (PS) during endoscopic retrograde cholangiopancreatography (ERCP) has been associated with a high risk of post-ERCP pancreatitis (PEP). This study aimed to examine the effect of no prophylaxis, somatostatin, rectal diclofenac and pancreatic duct (PD) stenting in reducing rates of PEP in patients who underwent early PS. METHODS: This was a retrospective comparative study and the study period was from January 2006 to December 2015. A standardized approach to early PS was used: (i) inadvertent guidewire cannulation of the PD>thrice; (ii) impacted bile duct stone; (iii) inability to achieve deep cannulation within 10 min. PEP prophylactic measures included: (i) none when there was minimal papilla trauma; (ii) somatostatin infusion; (iii) rectal diclofenac; (iv) PD stent. The difference in rates of PEP between the different strategies was analysed. RESULTS: During the study period, PS was performed in 191 ERCP patients (mean age 66 years; 56.5% males). The ERCP success rate after PS was 93.2% (178/191). Overall the PEP rate was 3.1% (6/191) and the severity in all cases was mild. PEP occurred in 6.1% of patients with PD cannulation but not in those without (P = 0.016). PEP rates were 1.8%, 7.3%, 1.8% and 0% in control, somatostatin, diclofenac and PD stenting groups, respectively (P = 0.209). CONCLUSIONS: There was no significant difference in PEP rates after early PS whether or not prophylactic measures were adopted if there was minimal papilla trauma. A trend towards lower PEP rates was observed in patients who had either rectal diclofenac or PD stenting, compared to somatostatin. [ABSTRACT FROM AUTHOR]

This study presents a systematic defect diagnosis to identify 'culprit physical features' that are potentially responsible for yield loss. A 'single location in‐a‐cluster' technique is proposed to diagnose multiple defects that may not be diagnosed by traditional 'single location at‐a‐time' technique. A statistics technique, 'analysis of variance', is conducted to reduce noise from random defects. Simulations on five ISCAS'89 circuit demonstrate the effectiveness of the authors' techniques. An experiment on an industrial design manufactured in 55 nm technology discovered a suspected culprit physical feature. [ABSTRACT FROM AUTHOR]

In this work, a novel lithium-sulfur battery was developed comprising Li2S as the cathode, lithium metal as the anode and polysulfide-based solution as the electrolyte. The electrochemical performances of these Li2S-based cells strongly depended upon the nature of the electrolytes. In the presence of the conventional electrolyte that consisted of lithium bis(trifluoromethanesulfonyl)- imide (LiTFSI) salt dissolved in a solvent combination of dimethoxyethane (DME)/1,3-dioxolane (DOL), the Li/Li2S cells showed sluggish kinetics, which translated into poor cycling and capacity retention. However, when using small amounts of polysulfides in the electrolyte along with a shuttle inhibitor the Li2S cathode was efficiently activated in the cell with the generation of over 1000 mAhg-1 capacity and good cycle life. [ABSTRACT FROM AUTHOR]

A physiologically-based pharmacokinetic model was developed for the disposition of 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) in 2 fish species-fathead minnow and medaka. The model was developed based on the empirical data on disposition of dioxins in fish tissues, as well as existing knowledge on the mechanisms of uptake, distribution, storage, and elimination of dioxins in various species (other than fish). The present study examined the applicability of mechanisms known to occur in other species for fish and concluded that the same mechanisms defined for disposition of 2,3,7,8-TCDD in (mostly) rodents can be applicable for the 2 fish species examined as well. Parameter values for the model were selected and/or calibrated using available databases. Model compartments included the gill, kidney, liver, and other richly-perfused tissues, as well as fat and other slowly-perfused tissues. The model was calibrated using 2 independent datasets for exposure of fathead minnow and medaka to 2,3,7,8-TCDD in water. The initial values of the model parameters were selected from several sources, and calibrated to represent the 2 exposure datasets. With very few exceptions, the estimated parameter values for the 2 species were comparable, and the final predictions were in strong agreement with the observations. The model developed in the present study can therefore be used in the prediction of the body burden of 2,3,7,8-TCDD in fathead minnow and medaka. Uncertainty in the model prediction as a result of variability in input parameters is discussed for the parameters with the highest impacts on the model outcome. Environ Toxicol Chem 2014;33:1064-1071. © 2014 SETAC [ABSTRACT FROM AUTHOR]

ABSTRACT A liquid chromatography tandem mass spectrometry (LC/MS/MS) method was developed and validated for the determination of five total tobacco-specific N-nitrosamines (TSNA), including free and conjugated forms in urine. The limits of detection for 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol, N′-nitrosonornicotine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, N′-nitrosoanatabine and N′-nitrosoanabasine were 0.6, 0.6, 10.0, 0.4 and 0.4 pg/mL, respectively, with a linear calibration range of up to 20,000 pg/mL. Intra- and inter-day precision for TSNA measurements ranged from 0.82 to 3.67% and from 2.04 to 7.73% respectively. For total TSNAs, the β-glucuronidase amount was optimized for hydrolysis time and yield. Different liquid chromatography columns and mobile phases with different pH conditions were evaluated. The validated method was then applied to 50 smoker and 30 nonsmoker urine samples. Our results suggest that this sensitive and relatively simple analytical method is suitable for application to epidemiological investigations of health risks associated with the exposure to tobacco smoke or secondhand smoke in both smokers and nonsmokers. Published 2013. This article is a U.S. Government work and is in the public domain in the USA. [ABSTRACT FROM AUTHOR]

Interleukin 17A IL-17A is a crucial immunomodulator in various chronic immunological diseases including rheumatoid arthritis and inflammatory bowel disease. The cytokine has also been demonstrated to control the pathogenesis of the Mycobacterium tuberculosis by dysregulating production of cytokines and chemokines and promoting granuloma formation. Whether IL-17A regulates innate defence mechanisms of macrophages in response to mycobacterial infection remains to be elucidated. In the current report, we investigated the effects of IL-17A on modulating the intracellular survival of Mycobacterium bovis bacillus Calmette-Guérin ( BCG) in RAW264.7 murine macrophages. We observed that IL-17A pre-treatment for 24 hr was able to synergistically enhance BCG-induced nitric oxide ( NO) production and inducible nitric oxide synthase expression in dose- and time-dependent manners. We further delineated the mechanisms involved in this synergistic reaction. IL-17A was found to specifically enhanced BCG-induced phosphorylation of Jun N-terminal kinase ( JNK), but not of extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein kinase. By using a specific JNK inhibitor (SP600125), we found that the production of NO in BCG-infected macrophages was significantly suppressed. Taken together, we confirmed the involvement of the JNK pathway in IL-17A-enhanced NO production in BCG-infected macrophages. We further demonstrated that IL-17A significantly enhanced the clearance of intracellular BCG by macrophages through an NO-dependent killing mechanism. In conclusion, our study revealed an anti-mycobacterial role of IL-17A through priming the macrophages to produce NO in response to mycobacterial infection. [ABSTRACT FROM AUTHOR]

To overcome the cycling instability and inefficiency that are inherent to lithium–sulfur batteries, a conceptually new approach is adopted based on mitigating the sulfur loss by creating a dynamic equilibrium between the dissolution and precipitation of lithium polysulfides at the electrode interface. Novel lithium polysulfide electrolytes that play a major role in self‐healing lithium–sulfur batteries are developed. [ABSTRACT FROM AUTHOR]

Synthetic progestins such as levonorgestrel (LNG) are used in combination with testosterone (T) in male contraceptive clinical trials to suppress gonadotropins secretion, but whether progestins have additional direct effects on the testis are not known. This study aimed to examine the effect of a potent progestin, (LNG), alone or in combination with testosterone (T) on spermatogenesis in adult rats, and to evaluate the functional role of the progesterone receptors (PRs) in the testis. In comparison with a low dose of LNG treatment in adult rats for 4 weeks, T and T + LNG treatment decreased testicular sperm count to 64.1 and 40.2% of control levels respectively. LNG induced germ cell apoptosis at stages I-IV and XII-XTV; T increased apoptosis at stages VII-VIII; LNG + T treatment induced greater germ cell apoptosis at a wider range of seminiferous epithelial stages. RT-PCR and Western Blots showed that PR was present in testes and up-regulated during suppression of spermatogenesis induced by testicular hormonal deprivation. PR knockout (PRKO) mice had larger testes, greater sperm production, increased numbers of Sertoli and Leydig cells. Suppression of gonadotropin and intratesticular T by GnRH-antagonist treatment induced PR promoter driven LacZ expression in Leydig cells of PRKO mice. This suggests that GnRH-antagonist treatment while inducing germ cell apoptosis also up-regulates PR. We conclude that (i) LNG + T induced greater suppression of spermatogenesis through increase in germ cell apoptosis involving a wider range of seminiferous epithelial stages than either treatment alone, (ii) up-regulation of PR was associated with inhibition of spermatogenesis, (iii) PR knockout mice showed increased sperm production suggesting that testicular PR activated events play a physiological and pharmacological inhibitory role in the testis. These data support the hypothesis that in addition to its known suppressive effects on gonadotropins, progestins may have direct inhibitory actions on the testis. [ABSTRACT FROM AUTHOR]

Background: Although the association of the dopamine transporter (DAT1) gene and attention-deficit/hyperactivity disorder (ADHD) has been widely studied, far less is known about its potential interaction with environmental risk factors. Given that maltreatment is a replicated risk factor for ADHD, we explored the interaction between DAT1 and maltreatment with ADHD symptoms defined dimensionally and using latent class analysis (LCA). Method: We tested the association of the 40 base-pair variable number of tandem repeats polymorphism in DAT1, maltreatment, and their interaction in 2,488 boys and girls from the National Longitudinal Study of Adolescent Health. Results: In boys, ADHD symptoms were optimally defined by four classes (Combined, Hyperactive/Impulsive, Inattentive, and Normal), whereas in girls, ADHD symptoms were defined by three classes (Combined, Combined-Mild, Normal). A significant DAT1 × maltreatment interaction revealed that maltreated girls homozygous for the 10-repeat allele had more symptoms of ADHD, and were also 2.5 times more likely to be classified in the Combined ADHD group than in the Normal Group. Conclusions: The underlying structure of ADHD symptoms differed between boys and girls and DAT1 interacted with maltreatment to predict ADHD symptoms and ADHD status derived from LCA. Interactive exchanges between maltreatment and DAT1 for ADHD symptoms, and their implications for intervention, are discussed. [ABSTRACT FROM AUTHOR]

Although multiple dimensions of negative parenting behavior are associated with childhood conduct problems ( CP), there is relatively little research on whether the association is equally robust in boys and girls. To improve the specificity of current models of negative parenting and offspring CP, we explored the potential moderating role of child sex in a sample of 179 5- to 10-year-old ethnically diverse boys and girls with and without attention-deficit/hyperactivity disorder ( ADHD) who were assessed using multiple methods (i.e., rating scales, semistructured interviews) and informants (i.e., parents, teachers). Controlling for children's age, race-ethnicity, and ADHD diagnostic status (i.e., ADHD vs. non- ADHD), inconsistent discipline was positively associated with offspring aggression and rule-breaking behavior, whereas harsh punishment was positively associated with aggression, rule-breaking behavior, and oppositional defiant disorder symptoms. Furthermore, child sex significantly moderated the association of inconsistent discipline and aggression and rule-breaking behavior, such that inconsistent discipline was positively associated with CP for boys, but not for girls. Given the centrality of negative parenting to theories of and efficacious interventions for aggression and CP, we discuss these findings within a developmental psychopathology framework and consider their implications for intervention. Aggr. Behav. 38:239-251, 2012. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Summary 1. As parasites can dramatically reduce the fitness of their hosts, there should be strong selection for hosts to evolve and maintain defence mechanisms against their parasites. One way in which hosts may protect themselves against parasitism is through altered behaviours, but such defences have been much less studied than other forms of parasite resistance. 2. We studied whether monarch butterflies ( Danaus plexippus L.) use altered behaviours to protect themselves and their offspring against the protozoan parasite Ophryocystis elektroscirrha (, Journal of Protozoology, 17, p. 300). In particular, we studied whether (i) monarch larvae can avoid contact with infectious parasite spores; (ii) infected larvae preferentially consume therapeutic food plants when given a choice or increase the intake of such plants in the absence of choice; and (iii) infected female butterflies preferentially lay their eggs on medicinal plants that make their offspring less sick. 3. We found that monarch larvae were unable to avoid infectious parasite spores. Larvae were also not able to preferentially feed on therapeutic food plants or increase the ingestion of such plants. However, infected female butterflies preferentially laid their eggs on food plants that reduce parasite growth in their offspring. 4. Our results suggest that animals may use altered behaviours as a protection against parasites and that such behaviours may be limited to a single stage in the host-parasite life cycle. Our results also suggest that animals may use altered behaviours to protect their offspring instead of themselves. Thus, our study indicates that an inclusive fitness approach should be adopted to study behavioural defences against parasites. [ABSTRACT FROM AUTHOR]

Soluble growth factors play an important role in the coordination and integration of cell proliferation, differentiation, fate determination, and morphogenesis during development of multicellular organisms. Fibroblast growth factors (FGFs) are a large family of polypeptide growth factors that are present in organisms ranging from nematodes to humans. RNA alternative splicing of FGFs and their receptors further enhances the complexity of this ligand-receptor system. The mouse Fgf8 gene produces eight splice variants, which encode isoform proteins with different N-termini and distinct receptor-binding affinity and biological activity. In this article, we review the roles of Fgf8 in vertebrate development and summarize the recent findings on the in vivo function of different Fgf8 splice variants. We propose that multiple Fgf8 isoform proteins act in concert to regulate the overall function of Fgf8 and account for the diverse and essential role of Fgf8 during vertebrate development. J. Cell. Physiol. 226: 1722-1726, 2011. © 2010 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

The human immunodeficiency virus (HIV) Tat protein has multiple regulatory roles, including trans-activation of the HIV genome and regulation of immune signalling processes, including kinase activation and cytokine expression. We recently demonstrated that HIV-1 Tat induces the expression of interleukin (IL)-10 via p38 mitogen-activated protein kinase (MAPK) activation. We further delineated that the Tat-responsive element of the IL-10 promoter was located within 625 to 595 bp upstream from the transcription start site. Using electrophoretic mobility shift assays, the transcription factors Ets-1 and Sp-1 were shown to bind to the IL-10 promoter to activate transcription of the gene. Furthermore, sequential deletional mutations of the Ets-1- and Sp-1-binding sites in the −625/−595 region reduced the DNA binding and transcription activity of the IL-10 promoter. Our results also showed that both the Tat-induced and Ets-1-regulated IL-10 promoter-driven luciferase activity can be abrogated by inhibitors of the p38 MAPK activity. In conclusion, the coordinated activities of p38 MAPK and the transcription factors, Ets-1 and Sp-1, may play an important role in the HIV-1 Tat-induced IL-10 transcription. [ABSTRACT FROM AUTHOR]

Objectives: To develop an anatomically and functionally based approach to endoscopic intranasal ethmoidectomy; to develop such an approach using the salient features of the anterior-to-posterior (AP) and posterior-to-anterior (PA) intranasal sinus operations; to assess the safety of this form of ethmoidectomy in a patient population. Study Design: Retrospective chart review of patients undergoing ethmoidectomy by the authors or by residents under their direct supervision. Setting: University teaching hospital. Results: Two thousand three hundred and forty-four patients underwent either unilateral or bilateral ethmoidectomies between April 1992 and August 2005. A complication rate of 0.34% was observed. Conclusions: Combining an AP approach to conserve sinus anatomy with a PA approach to avoid surgery directed toward the skull base provides a functional and safe procedure, as demonstrated by the reported results. [ABSTRACT FROM AUTHOR]

Abstract: HIV Tat has been known to have multiple regulatory roles including replication of HIV and modulation of cellular kinases. We investigated whether signaling kinase PKR plays a critical role in mediating Tat-induced cytokine dysregulation. We showed Tat induction of IL-10 dysregulation is associated with PKR activation. To examine the mechanism involved, inhibition of PKR activity abrogated the Tat-induced cytokine induction. We next identified that the MAP kinases including ERK-1/2 and p38 are downstream of PKR in these Tat-induced pathways. Thus, PKR may play a critical role in mediating the subversive effects of HIV Tat resulting in IL-10 induction. [Copyright &y& Elsevier]

Background: Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS) has been described as a specific sequela of allogeneic HPC transplantation (HPCT). Nevertheless, because multiple transplant-related sequela can cause the characteristic clinical features of TTP-HUS, the diagnosis is difficult.Study Design and Methods: All English-language articles describing patients with TTP-HUS following HPCT were identified. Articles reporting five or more total patients, including at least one patient diagnosed with TTP-HUS following allogeneic HPCT, were reviewed. All articles describing autopsies of patients diagnosed with TTP-HUS following allogeneic HPCT were also reviewed.Results: Thirty-five articles reporting 5 or more total patients described 447 patients diagnosed with TTP-HUS following allogeneic HPCT. The frequency of diagnosis of TTP-HUS following allogeneic HPCT varied by 125-fold (0.5%-63.6%). Twenty-eight different sets of diagnostic criteria were described in the 35 articles; 25 articles included both RBC fragmentation and increased serum LDH. Many risk factors described as correlating with the diagnosis of TTP-HUS also predict greater risk for multiple transplant-related complications. Benefit of plasma exchange treatment could not be documented. Survival information was reported for 379 patients, 232 (61%) died, and reported mortality rates varied from 0 to 100 percent. Autopsies have been reported for 35 patients who were diagnosed with TTP-HUS following allogeneic HPCT; none had systemic thrombotic microangiopathy, the diagnostic abnormality of TTP-HUS; and infection (19 patients) was the most commonly reported cause of death.Conclusions: The clinical features of TTP-HUS following allogeneic HPCT may be caused by common transplant-related complications; the benefit from plasma exchange treatment is uncertain. [ABSTRACT FROM AUTHOR]

The traditional quantity discount problem is analyzed from the perspective of game theory, including both noncooperative and cooperative models. For the noncooperative case, the Stackelberg equilibrium is derived. For the cooperative case, the Pareto Optimality criteriaare used to find a group of optimal strategies. Both scenarios are illustrated through an example which quantifies the benefits resulting from cooperation between the buyer and the seller for game-theoretic solutions using geometric programming. [ABSTRACT FROM AUTHOR]

Objectives: To display time-series firing rate and recruitment data for multiple, simultaneously active motoneurons activating human laryngeal muscles. These data provide specific information about how laryngeal muscle force is being controlled by the central nervous system at the level of the lower motoneuron., Methods: A quadrifilar needle electrode was used to record multi-channel myoelectric signals from thyroarytenoid muscle of normal subjects during tasks ranging from quiet breathing to a short sentence. Motor unit action potentials of the signal space were identified and tracked throughout task productions using pattern recognition and Precision Decomposition software., Results: We present the first recordings and analyses of multiple motor unit activations in the larynx. The firing times and mean firing rates are plotted for each identified motor unit, which reveal recruitment and decruitment information and the database from which common firing statistics across motor units may be derived., Conclusions: This study provides new information about neuromuscular physiology of the larynx. Specifically, the results reveal the ordered recruitment and firing patterns of multiple motor units and the existence of common drive from the central nervous system. The technique may prove fundamental to understanding various neuromuscular pathologies such as laryngeal spasm and to assist clinical prognosis of laryngeal paresis and the diagnosis of certain neurogenic disorders.