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The efficacy of endoscopic resection in early-stage esophageal squamous cell carcinoma has not been defined.We queried the National Cancer Database to identify patients presenting with cT1N0M0 esophageal squamous cell cancer between 2004 and 2017. Transitive match methods were used to 1:1:1 propensity match patients undergoing endoscopic resection to patients undergoing esophagectomy and those undergoing definitive chemoradiotherapy. Kaplan Meier method was used to compare 5-year overall survival profiles for matched cohorts.301 patients (19%) underwent endoscopic resection; 497 (32%) esophagectomy; 767 (49%) chemoradiation. On comparison of matched cohorts, patients undergoing chemoradiation demonstrated lower rates of survival than those undergoing esophagectomy (32% vs. 59%, p 0.0001) while those undergoing endoscopic resection demonstrated rates comparable to patients undergoing esophagectomy (53% vs. 59%, p = 0.77).For cT1N0M0 esophageal squamous cell cancer, endoscopic resection is associated with rates of survival similar to those following esophagectomy and better than those following definitive chemoradiation.

Human-aided invasion of alien species across the world sometimes leads to economic, health or environmental burdens. During invasion process, species encounter new environments and partially escape some ecological constrains they faced in their native range, while they face new ones. The Asian tiger mosquitoAedes albopictusis one of the most iconic invasive species that was introduced in every inhabited continent over a short period of time due to international trade. It has also been shown to be infected by a prevalent and yet disregarded gregarine entomoparasiteAscogregarina taiwanensis. In this study, we aimed at deciphering the global dynamics ofAs. taiwanensisinfection in naturalAe. albopictuspopulations and we further explored factors shaping its distribution. We showed thatAe. albopictuspopulations are highly colonized by severalAs. taiwanesisgenotypes but recently introduced ones are escaping the parasite. We further performed experiments to explain such pattern. First, we hypothesized that founder effects (i.e.population establishment by a small number of individuals) may influence the parasite dynamics. This was confirmed since experimental increase in mosquitoes’ density improves the parasite horizontal transmission to larvae. Furthermore,Ae. albopictuslarvae do not exhibit density dependent prophylaxis to control the parasite meaning that infection is not mitigated when larval density increases. Secondly, we hypothesized that unparasitized mosquitoes were more prompt to found new populations through active flight dispersal. This was, however, unlikely since parasitized mosquitoes tend to be more active than their unparasitized relatives. Finally, we hypothesized that mosquito passive dispersal (i.e.often mediated by human-aided transportation of dried eggs) affects the parasite infectiveness. Our results support this hypothesis since parasite infection decreases over time when dry eggs are stored. This study highlights the importance of global trade on parasitism escape in one of the most invasive vector species on earth.

Latines have higher rates of eating disorders characterized by binge eating compared to their non-Latine white counterparts, yet culturally and socially relevant factors related to binge eating in Latines have been largely understudied. The purpose of the current study was to examine how discrimination and acculturative stress were associated with binge eating in a nationally representative sample of Latines. An additional aim was to test the extent to which family cohesion and social support could buffer against the effects of discrimination and acculturative stress on binge eating.Participants (56% female, N = 2550) were Latines enrolled in the National Latino and Asian American Study. Structural equation modeling using 1000 re-sampled data sets built from machine learning iterative sampling procedures was used to examine the effects of discrimination, acculturative stress, family cohesion, and social support on binge eating.Results indicated that only discrimination was significantly associated with binge eating. Neither the direct effect of acculturative stress, interaction of family cohesion and acculturative stress, interaction of social cohesion and acculturative stress, nor the interaction of social support and discrimination were significantly associated with binge eating.This study highlights the need for mental-health providers to understand and assess discrimination among Latines presenting with concerns of binge eating. Treatments that effectively provide coping strategies to manage discriminatory experiences and reduce binge eating could improve both effectiveness of treatment and retention rates for Latine individuals with binge eating.This study examined the association of discrimination, acculturative stress, family cohesion, and social support with binge eating in Latines. Only discrimination was significantly associated with binge eating, highlighting the importance for providers to assess discrimination among Latines with binge-eating concerns and to improve equity, inclusion, and belonging at a societal level. Modifying existing treatments to address coping with discrimination could improve the effectiveness for Latines with binge-eating concerns.

Studies evaluating endoscopic resection for early-stage (cT1N0M0) esophageal adenocarcinoma include small numbers of patients with T1b tumors. The role of endoscopic resection in esophageal adenocarcinoma remains incompletely defined.We queried the National Cancer Database to identify patients presenting with esophageal adenocarcinoma between 2010 and 2017. Those treated with neoadjuvant chemoradiotherapy and endoscopic ablation were excluded. Patients undergoing endoscopic resection for cT1a and cT1b tumors were separately 1:1 propensity matched for relevant demographic and tumor factors to those undergoing esophagectomy for disease of like clinical stage. The Kaplan-Meier method was used to compare 5-year overall survival for matched cohorts.A total of 3,157 patients met the inclusion criteria. Of these patients, 2,024 (64.1%) had cT1a and 1133 (35.9%) had cT1b disease. Among those with cT1a tumors, 461 (22.8%) underwent esophagectomy, 1,357 (67.0%) endoscopic resection, and 206 (10.2%) treatment with chemoradiotherapy alone. Among those with cT1b tumors, 649 (57.3%) underwent esophagectomy, 293 (25.9%) endoscopic resection, and 191 (16.8%) chemoradiotherapy. On unadjusted comparison, patients treated for esophageal adenocarcinoma with chemoradiotherapy had a lower rate of overall survival than those treated with endoscopic resection or esophagectomy (26.1% vs 73.1% vs 75.5%, P.001). On comparison of matched cohorts, patients undergoing endoscopic resection for cT1b tumors demonstrated lower rates of overall survival than those undergoing esophagectomy (60.6% vs 74.1%, P = .0013), whereas those undergoing endoscopic resection for cT1a tumors demonstrated rates of overall survival statistically similar to those undergoing esophagectomy (77.8% vs 80.2%, P = .75).Esophagectomy is associated with improved overall survival relative to endoscopic resection in patients presenting with cT1bN0M0 but not in those with cT1a esophageal adenocarcinoma.

Although bony defects of the tegmen surface are relatively common, the majority of dehiscences are asymptomatic. For those who experience symptoms, there is a wide spectrum of relatively benign manifestations such as hearing loss and otorrhea to potentially more serious but rare sequelae such as epilepsy and meningitis. Surgical management of tegmen dehiscences (TDs) can help prevent these symptoms. In this manuscript, we present one of the largest reported single team experiences of using a temporal craniotomy with middle cranial fossa approach and temporalis fascia graft in the treatment of tegmen defects.We retrospectively reviewed every case of a TD surgically repaired by the same neurosurgeon/otolaryngologist team at Loyola University Medical Center from May 2015 to January 2022. In our chart review, we identified 44 patients with 48 cases of tegmen defect repair. We analyzed patient characteristics, operative details, and postoperative outcomes.44 patients met inclusion criteria for the presence of TD (mean age 55 years, 55% male, and average body mass index 35.6). 89% of these patients had no clear etiology for the dehiscence. Commonly reported symptoms were hearing loss (89%) and CSF otorrhea (82%). The least reported presenting signs and symptoms were seizures (5%) and meningitis (2%). Most defects were repaired with both temporalis fascial and calvarial bone grafts (63%), while a minority were treated with temporalis fascia only (33%), temporalis fascia with muscle (2%), or fascia lata (2%). Every patient in our sample experienced resolution of CSF otorrhea after tegmen repair and 81% of the sample reported subjective hearing improvements after surgery. 6% of our sample had post-operative infections and 8% of patients underwent repeat unilateral surgery for a surgical complication.Craniotomy for middle fossa approach using autologous temporalis fascial grafts is a safe and effective method for the treatment of TD. These procedures should be performed by experienced and multidisciplinary teams.

Communicating one's mindset means transmitting complex relationships between concepts and emotions. Using cognitive network science, we reconstruct the mindset around suicide as communicated in 139 genuine suicide notes. Despite their negative context, suicide notes are surprisingly positively valenced and their ending statements are markedly more emotional, i.e. elicit deeper fear/sadness but also stronger joy/trust and anticipation, than their main body. By using emotional states from the Emotional Recall Task, we "open the lid" of suicidal narratives and compare their emotional backbone against emotion recall in mentally healthy individuals. Supported by psychological literature, we introduce emotional complexity as an affective analogue of structural balance theory, measuring how elementary cycles (closed triads) of emotion co-occurrences mix positive, negative and neutral states in narratives and recollections. Both authors of suicide notes and healthy individuals exhibit less complexity and more emotional coherence than expected by chance. However, suicide narratives display higher complexity, i.e. a lower level of coherently valenced triads, than healthy individuals recalling the same states. Entropy measures identified a similar tendency for suicide letters to shift more frequently between contrasting emotional states. Our results demonstrate that suicide notes possess highly contrastive narratives of emotions, more complex than expected by null models and healthy populations.

Widespread messages use metaphoric language and imagery to prompt recipients to interpret health-related concepts in terms of dissimilar, familiar concepts (e.g., "fight the war on cancer"). When do these messages work? According to Conceptual Metaphor Theory, thinking metaphorically involves looking past concepts' superficial differences to identify their similarities at a structural level. Thus, we hypothesized that when people's general construal mindset is oriented to focus on information's abstract meaning, not its concrete details, they would process a metaphor's target health concept in ways that correspond to the dissimilar concept. Accordingly, after priming an abstract, but not concrete, construal mindset: framing sun exposure as enemy confrontation (vs. literally) increased cancer risk perceptions and sun-safe intentions (Study 1; N=186); and framing smoking cessation as an arduous journey (vs. literally) increased appreciation of quitting difficulties and interest in cessation tools (Study 2; N=244). We discuss practical and theoretical implications for improving health communication.

ObjectiveTo examine the impact of central nervous system (CNS) stimulants on the growth of children with attention-deficit/hyperactivity disorder (ADHD), and to assess the efficacy and feasibility of weight recovery interventions on growth.MethodA total of 230 children aged 5 to 12 years with ADHD with no history of chronic CNS stimulant use were randomly assigned to receive daily CNS stimulants (78%, primarily osmotic release oral system-methylphenidate [OROS-MPH]) or behavioral treatment (22%) for 30 months. After 6 months, children evidencing a decline in body mass index (BMI) of >0.5 z-units were randomized to 1 of 3 weight recovery treatments (WRTs): monthly monitoring of height/weight (MON) plus continued daily medication; drug holidays (DH) with medication limited to school days; or daily caloric supplementation (CS) with a 150-kcal supplement plus daily medication.ResultsBefore WRT assignment, medication was associated with significant reductions in standardized weight and height (p values&nbsp

Inflammation has been implicated in the pathogenesis and maintenance of depressive symptoms. The role of inflammation in depressive symptomatology may be complex, varying within endophenotypes and across the lifespan. Aging is associated with myriad changes in the structure and function of the brain. Yet, little attention has been given to the role of inflammation in depressive symptoms within a lifespan developmental framework. In this study, we examined whether the association between inflammation and depressive symptom domains varied by age. Participants were a community sample of individuals (N= 2,077, Range = 30–84) who participated in the Biomarker projects of the MIDUS2, MIDUS Refresher, or the MIDJA study. Inflammation was indexed by two inflammatory markers consistently implicated in depressed individuals, interleukin 6 (IL-6) and C-reactive protein (CRP), measured in blood. Depressive symptom domains, including depressed affect, anhedonia, somatic complaints, and interpersonal problems, were reportedviathe Center for Epidemiologic Studies—Depression Scale (CES-D). Inflammatory markers were associated with more somatic complaints, more interpersonal problems, and less anhedonia. Age moderated the relationship between inflammatory markers and two depressive symptom subscales. Specifically, the positive association between inflammation and somatic complaints and the negative association between inflammation and anhedonia increased with age. These observations offer preliminary evidence from a large community sample that aging may be an important context for the role of inflammatory signaling in different aspects of psychological and behavioral well-being.

Understanding the cognitive and emotional perceptions of people who commit suicide is one of the most sensitive scientific challenges. There are circumstances where people feel the need to leave something written, an artifact where they express themselves, registering their last words and feelings. These suicide notes are of utmost importance for better understanding the psychology of suicidal ideation. This work gives structure to the linguistic content of suicide notes, revealing interconnections between cognitive and emotional states of people who committed suicide. We build upon cognitive network science, psycholinguistics and semantic frame theory to introduce a network representation of the mindset expressed in suicide notes. Our cognitive network representation enables the quantitative analysis of the language in suicide notes through structural balance theory, semantic prominence and emotional profiling. Our results indicate that the emotional syntax connecting positively- and negatively-valenced terms gives rise to a degree of structural balance that is significantly higher than null models where the affective structure was randomized. We show that suicide notes are affectively compartmentalized such that positive concepts tend to cluster together and dominate the overall network structure. A key positive concept is "love", which integrates information relating the self to others in ways that are semantically prominent across suicide notes. The emotions populating the semantic frame of "love" combine joy and trust with anticipation and sadness, which connects with psychological theories about meaning-making and narrative psychology. Our results open new ways for understanding the structure of genuine suicide notes informing future research for suicide prevention., Significantly revised version (in particular balance analysis); 22 pages (with SI); 5 figures; 2 tables

Adolescence is a common period for eating disorder (ED) onset. The availability of psychometrically sound measures of ED psychopathology enables clinicians to accurately assess symptoms and monitor treatment outcomes continuously from adolescence and adulthood. The purpose of this study was to assess if the Eating Pathology Symptoms Inventory (EPSI) is invariant across adolescents and adults. Participants (N = 29,821) were adolescent (n = 5250) and adult (n = 24,571) users of the Recovery Record (RR) mobile phone application who provided EPSI responses through the application. Measurement invariance testing was conducted to assess invariance of the EPSI Body Dissatisfaction, Restricting, Excessive Exercise, Purging, Cognitive Restraint, and Binge Eating scales across adolescents (age 13 through 17) and adults (age 18 and older). Findings indicated that all EPSI factors administered in the RR app replicated in both adolescent and adult users. The EPSI factor structure was largely equivalent in adolescents and adults, demonstrating evidence for configural and metric invariance, as well as some evidence for scalar invariance. Our results indicated that EPSI scales measured the same constructs across development. Clinicians and researchers may benefit from utilizing the EPSI to measure ED psychopathology in adolescents and for continued progress monitoring into adulthood.

Previous research has failed to find differences in eating disorder and general psychopathology and impairment between people with sub- and full-threshold bulimia nervosa (BN). The purpose of the current study was to test the validity of the distinction between sub- and full-threshold BN and to determine the frequency of objective binge episodes and inappropriate compensatory behaviors that would best distinguish between sub- and full-BN. Community-recruited adults (83.5% female) with current sub-threshold (n = 105) or full-threshold BN (n = 99) completed assessments of eating-disorder psychopathology, clinical impairment, internalizing problems, and drug and alcohol misuse. Receiver operating characteristic curve analysis was used to evaluate whether eating-disorder psychopathology, clinical impairment, internalizing problems, and drug and alcohol misuse could empirically discriminate between sub- and full-threshold BN. The frequency of binge episodes and inappropriate compensatory behaviors (AUC = 0.94) was “highly accurate” in discriminating between sub- and full-threshold BN; however, only objective binge episodes was a significant predictor of BN status. Internalizing symptoms (AUC = 0.71) were “moderately accurate” at distinguishing between sub- and full-BN. Neither clinical impairment (AUC = 0.60) nor drug (AUC = 0.56) or alcohol misuse (AUC = 0.52) discriminated between groups. Results suggested that 11 episodes of binge eating and 17 episodes of inappropriate compensatory behaviors optimally distinguished between sub- and full-BN. Overall, results provided mixed support for the distinction between sub- and full-threshold BN. Future research to clarify the most meaningful way to discriminate between sub- and full-threshold is warranted to improve the criterion-related validity of the diagnostic system.

There has been a paradigm shift in higher education towards the utilisation of problem-based learning sessions instead of the traditional lecture format which is considered obsolete by detractors and simply convenient by its advocates. This move coincides with research highlighting that active learning strategies promote profound rather than superficial learning, encourage critical thinking and increase student attainment. However, there are limited studies quantifying the attainment of undergraduate students presented with varied pedagogical techniques, and still fewer that assess student perceptions of their own learning. Over four different teaching sessions (two lectures and two problem-based learning), n=94 students completed a 10 question questionnaire comprised of Likeart style questions assessing how advantageous they perceived the teaching strategy implemented to be to their own learning. In addition, n=64 of the students also completed short quizzes at the completion of three out of four of the sessions (one lecture, two problem-based learning sessions) assessing their knowledge of the content covered. There was no significant difference in attainment (quiz score) between the two delivery methods (p = 0.113), however there was a significant difference between individual sessions (p

Conceptual metaphor theory offers a perspective on how and when people find meaning in life. Whereas life’s meaning can be difficult to grasp, metaphor compares life to a relatively more concrete a...

// Xinhua Chen 1, * , Yiling Chen 2, * , Jianwen Jiang 1 , Liming Wu 1 , Shengyong Yin 1 , Xudong Miao 3 , Robert J. Swanson 4 and Shusen Zheng 1 1 Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University, Zhejiang, 310003, China 2 The Department of Anatomy, Tianjin Medical University, Tianjin, 300070, China 3 The Department of Orthopedics, The Second Affiliated Hospital, Zhejiang University, Zhejiang, 310003, China 4 Anatomical Sciences Department, College of Osteopathic Medicine, Liberty University, Lynchburg, VA, 24515, USA * These authors have contributed equally to this work Correspondence to: Shusen Zheng, email: shusenzheng@zju.edu.cn Xudong Miao, email: mxd5172@163.com Robert J. Swanson, email: rjswanson@liberty.edu Keywords: nano-pulse stimulation (NPS), nanosecond pulsed electric field (nsPEF), non-thermal, ablation, palliative therapy Abbreviations: nsPEF: nanosecond pulsed electric field; ALP: alkaline phosphatase; NPS: nano-pulse stimulation Received: December 16, 2016 Accepted: March 26, 2017 Published: April 18, 2017 ABSTRACT Background: Nanosecond pulsed electric field (nsPEF), which is also termed as nano-pulse stimulation (NPS), has the potential of stimulating immune responses toward cancer cells. The current study investigates its local and systemic antitumor efficacy in vivo in late stage tumors with lung metastasis. Method: The 12 canines with spontaneous osteosarcomas and 12 nude mice transplanted with human hepatocellular carcinoma were divided randomly and were given NPS treatment, surgery or no treatment control. Nanosecond pulsed electric field was delivered with puncture electrodes at 40 kV/cm with 500 pulses at 1 Hz. The survival time, tumor volume, serum alkaline phosphatase (ALP), joint capsule damage and lung metastasis were followed up. The efficacy was compared with control. Results: Nanosecond pulsed electric field reduced primary tumor volume and extended the survival significantly compared to the control group ( P

Time seems to speed up as one ages, and it affects how people find meaning in life and plan their future. What creates this perception? We examine the role of “chunking” – mentally bundling individual moments of experience under broad categories. With age, people group experiences into progressively bigger chunks (e.g., work, family). Consequently, fewer things seem to have occurred in a given period, so it seems to have passed faster in retrospect. Supporting this account, three studies (overall N = 324) show that people led to chunk (vs. not chunk) their past year perceived it as passing faster. The effect of chunking emerged reliably across converging operations and specifically accelerated the chunked period, not other periods. Furthermore, chunking increased the appeal of nostalgia, suggesting that processes that accelerate time instigate a compensatory urge to reflect on momentous occasions of one’s life. Implications for the “self across time” are discussed.

According to terror management theory, cultural worldviews function to mitigate mortality concerns. Looking closer, we observe that any specific cultural meaning system, such as national or religious identification, rests on nonspecific, domain-general conceptions of the world as structured—that is, simple, clear, consistent, and marked by a coherent relation of parts. If nonspecific structure provides the epistemic foundation for death-denying worldviews, then people would be expected to compensate for mortality concerns by projecting structure on their social and physical environments, even when no objective structure exists. Supporting this hypothesis, several studies show that mortality salience (MS) increases diverse tendencies to seek and prefer well-structured interpretations of social stimuli. For example, MS increases attraction to clear-cut stereotypes and predictable behavior, and it decreases liking for disordered time tables and visually chaotic artworks. Studies furthermore show that individuals disposed to prefer well-structured knowledge (typically measured with the Personal Need for Structure Scale) are especially likely to respond to MS by affirming nonspecific epistemic structure. This chapter reviews select findings from this emerging literature. Discussion looks across findings for ways to understand the deep-seated motives that drive people to project structure on the world and their lives.

This study investigated the role of milk fat globule-epidermal growth factor-factor 8 (MFGE8) in TGF-β-induced epithelial–mesenchymal transition (EMT) of endometrial epithelial cells. These were in vitro studies using human endometrial epithelial cells and mouse blastocysts. We investigated the ability of TGF-β to induce EMT in endometrial epithelial cells (HEC-1A) by assessment of cytological phenotype (by light and atomic force microscopy), changes in expression of the markers of cell adhesion/differentiation E- and N-cadherin, and of the transcription factor Snail (by immunofluorescence and immunoblotting), and competence to support embryo attachment in a mouse blastocyst outgrowth assay. We also studied the effects of E-cadherin expression in cells transfected by retroviral shRNA vectors specifically silencing MFGE8. Results demonstrated that TGF-β induced EMT as demonstrated by phenotypic cell changes, by a switch of cadherin expression as well as by upregulation of the expression of the mesenchymal markers Snail and Vimentin. Upon MFGE8 knockdown, these processes were interfered with, suggesting that MFGE8 and TGF-β together may participate in regulation of EMT. This study demonstrated for the first time that endometrial MFGE8 modulates TGF-β-induced EMT in human endometrium cells.

Many studies have been dedicated to hypertension and hypercholesterolemia, as they are the primary conditions that influence the unfolded protein response (UPR). However, the concurrent effects of these two factors are unknown. Our research used spontaneously hypertensive rats (SHR) fed a cholesterol enriched diet (CED) as model of atherosclerosis formation to discover what effect the simultaneous actions of hypertension and hypercholesterolemia have on the UPR. The combination of hypertension and consumption of a CED (not the CED alone) caused the formation of early atherosclerotic features. Both increased expression of the CCAAT-enhancer-binding protein (CHOP) and the insulin induced gene 1 (INSIG1), which is the target gene of the sterol regulatory element-binding protein 1-c (SREBP1-c), and decreased expression of the spliced x-box binding protein1 (sXBP1) mRNA were observed in the SHR fed a CED. Cholesterol overload strongly suppressed glucose regulated protein 78 (GRP78), glucose regulated protein 94 (GRP 94), and the expression of CHOP and INSIG1 mRNA in both normotensive and hypertensive rats. Unlike other UPR factors, the sXBP1 mRNA expression was strongly downregulated in SHR fed a normal diet but upregulated in those fed a CED. The changes to UPR in the SHR fed a CED were associated with improvement of the initially impaired heart function of the rats.

Twenty-two scientists met at Krobielowice, Poland, to discuss the impact of the social environment, spatial proximity, migration, poverty, but also psychological factors such as body perception and satisfaction, and social stressors such as elite sports, and teenage pregnancies, on child and adolescent growth. The data analysis included linear mixed effects models with different random effects, Monte Carlo analyses, and network simulations. The work stressed the importance of the peer group, but also included historic material, some considerations about body proportions, and growth in chronic liver, and congenital heart disease.

The perception that God controls one's life can bolster motivation to pursue personal goals, but it can also have no impact and even squelch motivation. To better understand how religious beliefs impact self-regulation, the current research built on Compensatory Control Theory's claim that perceiving the environment as predictable (vs. unpredictable) strengthens commitment to long-term goals. Perceiving God's intervention as following an understandable logic, which implies a predictable environment, increased self-reported and behavioral commitment to save money (Studies 1–3), excel academically (Study 4), and improve physical health (Study 5). In contrast, perceiving God as intervening in mysterious ways, which implies that worldly affairs are under control yet unpredictable, did not increase goal commitment. Exploratory mediational analyses focused on self-efficacy, response efficacy, and confidence in God's control. A meta-analysis (Study 6) yielded a reliable effect whereby belief in divine control supports goal pursuit specifically when it signals the predictability of one's environment.

To identify the secreted proteins of murine embryos grown in vitro. Two-cell mouse embryos (n = 432) were randomly allocated to culture to the blastocyst stage in protein-free and in protein-supplemented (3 % BSA) media. Proteins were separated by SDS-PAGE; bands were visualized by coomassie staining, followed by in-gel trypsin digestion and liquid chromatography-tandem mass spectrometry. RT-PCR and confocal microscopy were used to confirm gene/protein expression in blastocysts. Of all individually identified proteins, 34 and 23 were found in embryos cultured without and with BSA, respectively, and 20 were common. Identified proteins having an N-terminal secretory sequence or transmembrane domains located on the extracellular backbone were postulated as secreted proteins. Gene and protein expression for two selected molecules were confirmed. Functional analysis revealed over-represented processes related to lipid metabolism, cyclase activity, and cell adhesion/membrane functions. This study provided evidence to further characterize secreted proteins by mouse embryos grown from the 2-cell to the blastocyst stage in vitro. Because of homology between murine and human, these results may provide information to be translated to the clinical setting.

Horses are stabled overnight for a number of practical reasons; however, there is little research quantifying nocturnal equine behavioral patterns or the extent to which different environments influence nocturnal behavior. The aim of this study was to establish whether differences in duration of sleep and ingestive behaviors were apparent for horses bedded on straw (group 1) or shavings (group 2). Ten geldings of mixed breed (mean age: 7.3 ± 3.53 years) bedded on either shavings (n = 5) or straw (n = 5) were observed between 7 pm and 7 am. Duration of behaviors according to a predefined ethogram was recorded in minutes using a video recorder and continuous focal sampling. Mann–Whitney U tests were used to identify whether any significant differences in duration of ingestion and sleep behaviors occurred for horses bedded on straw compared with shavings. Of the total observation period, group 1 spent, on average, 29.3% of their time budget engaged in recumbent behaviors, compared with 12.2% for group 2. However, no significant differences in duration were established between horses bedded on straw or shavings for standing sleep, sternal recumbency, and lateral recumbency behaviors ( P > 0.05). Ingestive behaviors occupied approximately one-third of the time budget, with no significant difference ( P > 0.05) observed between groups. On average, group 1 spent a longer proportion of the observation period ingesting bedding (8.1%) compared with group 2 (1%). Duration of bedding ingestion appeared to peak between 1 am and 7 am for both groups. Although not quantified, general observations revealed horses were motivated to alternate between eating hay and bedding in both groups, owing to the prevalence of bedding ingestion. The results indicate that straw bedding facilitates the display of ingestive and sleep behaviors, whereas horses bedded on shavings spent a greater proportion of their nocturnal time budget engaged in "other" behaviors. Further research is required to investigate the extent to which different types of bedding material enrich the environment of horses that are stabled overnight.

Objective To compare educational, occupational, legal, emotional, substance use disorder, and sexual behavior outcomes in young adults with persistent and desistent attention-deficit/hyperactivity disorder (ADHD) symptoms and a local normative comparison group (LNCG) in the Multimodal Treatment Study of Children with ADHD (MTA). Method Data were collected 12, 14, and 16 years postbaseline (mean age 24.7 years at 16 years postbaseline) from 476 participants with ADHD diagnosed at age 7 to 9 years, and 241 age- and sex-matched classmates. Probands were subgrouped on persistence versus desistence of DSM-5 symptom count. Orthogonal comparisons contrasted ADHD versus LNCG and symptom-persistent (50%) versus symptom-desistent (50%) subgroups. Functional outcomes were measured with standardized and demographic instruments. Results Three patterns of functional outcomes emerged. Post−secondary education, times fired/quit a job, current income, receiving public assistance, and risky sexual behavior showed the most common pattern: the LNCG group fared best, symptom-persistent ADHD group worst, and symptom-desistent ADHD group between, with the largest effect sizes between LNCG and symptom-persistent ADHD. In the second pattern, seen with emotional outcomes (emotional lability, neuroticism, anxiety disorder, mood disorder) and substance use outcomes, the LNCG and symptom-desistent ADHD group did not differ, but both fared better than the symptom-persistent ADHD group. In the third pattern, noted with jail time (rare), alcohol use disorder (common), and number of jobs held, group differences were not significant. The ADHD group had 10 deaths compared to one death in the LNCG. Conclusion Adult functioning after childhood ADHD varies by domain and is generally worse when ADHD symptoms persist. It is important to identify factors and interventions that promote better functional outcomes.

The female reproductive system is described from its gross anatomical, histological, and physiological perspectives. The gross and microscopic anatomical structures described in this chapter ainclude (1) the primary reproductive gland, that is, the ovary; (2) the secondary reproductive glands, that is, bulbourethral, cervical, and vestibular; and (3) the tubular structures developing from the paramesonephric ducts (Mullerian ducts), that is, fallopian (uterian or ovarian) tubes, uterus, and vagina. The physiology of the female reproductive system describes how these various anatomical structures interact in a normal reproductively fertile adult woman. This function necessarily includes the reproductive portion of the hypothalamus and pituitary (hypophysis) gland.

This chapter presents an overview of the processes of fertilization, gestation, and parturition. Fertilization in humans is a well-orchestrated, highly specific set of events between an ovum and a spermatozoon. These events have begun to be elucidated in great detail over the past few decades.

A recent study has shown that nanosecond pulsed electric fields (nsPEF) can affect the intracellular structures of melanoma within weeks. nsPEF is a non-drug, non-thermal treatment using ultrashort, intense pulsed electric fields with nanosecond durations. In the current study we followed up melanoma histopathology and metastasis with tissue micro-array 5 months post-nsPEF. After nsPEF treatment, tumor growth, tumor histology, metastasis, peri-tumor vessel and micro-vessel density were examined for the effect of nsPEF treatment on melanoma in vivo. The 17 nsPEF-treated mice were tumor-free for 169 days, significantly longer than those 19 control mice bearing melanoma without nsPEF. Histopathology follow-up showed that melanoma did not recur to the primary injection place after complete elimination. Compared with the control tumor, nsPEF-treated tumors present decreased micro-vessel density in a time-course manner in this survival study. Treatment with nsPEF caused continuous histopathological changes in melanomas, eliminated melanoma without recurrence at the primary site and prolonged animal survival time by inhibiting tumor blood supply and leading to tumor infarction. Thus, nsPEF could be applied in a non-ionizing therapeutic approach, without other agents, to locally treat tumors within a defined boundary.

Darko Turic1, James Swanson2, Edmund Sonuga-Barke1,31Institute for Disorders of Impulse and Attention, School of Psychology, University of Southampton, UK; 2Child Development Center, University of California, Irvine, California, US; 3Department of Experimental, Clinical and Health Psychology, Ghent University, BelgiumAbstract: Attention deficit/hyperactivity disorder (ADHD) is a common and potentially very impairing neuropsychiatric disorder of childhood. Statistical genetic studies of twins have shown ADHD to be highly heritable, with the combination of genes and gene by environment interactions accounting for around 80% of phenotypic variance. The initial molecular genetic studies where candidates were selected because of the efficacy of dopaminergic compounds in the treatment of ADHD were remarkably successful and provided strong evidence for the role of DRD4 and DAT1 variants in the pathogenesis of ADHD. However, the recent application of noncandidate gene strategies (eg, genome-wide association scans) has failed to identify additional genes with substantial genetic main effects, and the effects for DRD4 and DAT1 have not been replicated. This is the usual pattern observed for most other physical and mental disorders evaluated with current state-of-the-art methods. In this paper we discuss future strategies for genetic studies in ADHD, highlighting both the pitfalls and possible solutions relating to candidate gene studies, genome-wide studies, defining the phenotype, and statistical approaches.Keywords: dopamine, ADHD, pharmacogenetics, candidate gene

Many effective anti-cancer strategies target apoptosis and angiogenesis mechanisms. Applications of non-ionizing, nanosecond pulsed electric fields (nsPEFs) induce apoptosis in vitro and eliminate cancer in vivo; however in vivo mechanisms require closer analysis. These studies investigate nsPEF-induced apoptosis and anti-angiogenesis examined by fluorescent microscopy, immunoblots, and morphology. Six hours after treatment with one hundred 300 ns pulses at 40 kV/cm, cells transiently expressed active caspases indicating that caspase-mediated mechanisms. Three hours after treatment transient peaks in Histone 2AX phosphorylation coincided with terminal deoxynucleotidyl transferase dUTP nick end labeling positive cells and pyknotic nuclei, suggesting caspase-independent mechanisms on nuclei/DNA. Large DNA fragments, but not 180 bp fragmentation ladders, were observed, suggesting incomplete apoptosis. Nevertheless, tumor weight and volume decreased and tumors disappeared. One week after treatment, vessel numbers, vascular endothelial growth factor (VEGF), platelet derived endothelial cell growth factor (PD-ECGF), CD31, CD35 and CD105 were decreased, indicating anti-angiogenesis. The nsPEFs activate multiple melanoma therapeutic targets, which is consistent with successes of nsPEF applications for tumor treatment in vivo as a new cancer therapeutic modality.

Nanosecond pulsed electric fields (nsPEFs) can affect the intracellular structures of cells in vitro. This study shows the direct effects of nsPEFs on tumor growth, tumor volume, and histological characteristics of normal skin and B16-F10 melanoma in SKH-1 mice. A melanoma model was set up by injecting B16-F10 into female SKH-1 mice. After a 100-pulse treatment with an nsPEF (40-kV/cm field strength; 300-ns duration; 30-ns rise time; 2-Hz repetition rate), tumor growth and histology were studied using transillumination, light microscopy with hematoxylin and eosin stain and transmission electron microscopy. Melanin and iron within the melanoma tumor were also detected with specific stains. After nsPEF treatment, tumor development was inhibited with decreased volumes post-nsPEF treatment compared with control tumors (P< 0.05). The nsPEF-treated tumor volume was reduced significantly compared with the control group (P < 0.01). Hematoxylin and eosin stain and transmission electron microscopy showed morphological changes and nuclear shrinkage in the tumor. Fontana–Masson stain indicates that nsPEF can externalize the melanin. Iron stain suggested nsPEF caused slight hemorrhage in the treated tissue. Histology confirmed that repeated applications of nsPEF disrupted the vascular network. nsPEF treatment can significantly disrupt the vasculature, reduce subcutaneous murine melanoma development, and produce tumor cell contraction and nuclear shrinkage while concurrently, but not permanently, damaging peripheral healthy skin tissue in the treated area, which we attribute to the highly localized electric fields surrounding the needle electrodes.

Objective: To review and provide details about the primary and secondary findings from the Multimodal Treatment study of ADHD (MTA) published during the past decade as three sets of articles. Method: In the second of a two part article, we provide additional background and detail required by the complexity of the MTA to address confusion and controversy about the findings outlined in part I (the Executive Summary). Results: We present details about the gold standard used to produce scientific evidence, the randomized clinical trial (RCT), which we applied to evaluate the long-term effects of two well-established unimodal treatments, Medication Management (MedMGT) and behavior therapy (Beh), the multimodal combination (Comb), and treatment “as usual” in the community (CC). For each of the first three assessment points defined by RCT methods and included in intent-to-treat analyses, we discuss our definition of evidence from the MTA, interpretation of the serial presentations of findings at each assessment point with a different definition of long-term varying from weeks to years, and qualification of the interim conclusions about long-term effects of treatments for ADHD based on many exploratory analyses described in additional published articles. Conclusions: Using a question and answer format, we discuss the possible clinical relevance of the MTA and present some practical suggestions based on current knowledge and uncertainties facing families, clinicians, and investigators regarding the long-term use of stimulant medication and behavioral therapy in the treatment of children with ADHD. (J. of Att. Dis. 2008; 12(1) 15-43)

This study applies stochastic frontier analysis to test the monopoly union model. This approach allows the use of a wider data set than has been previously employed. We fit a stochastic cost frontier to data from the U.S. manufacturing sector that includes exogenous sources of potential inefficiency including unionization. Our findings suggest that over the 1972–1982 time period, more heavily unionized industries in the U.S. manufacturing sector were more likely to operate off their labor demand curve. This result is inconsistent with the monopoly union model predictions.

The hamster is a useful model of human reproductive biology because its oocytes are similar to those in humans in terms of size and structural stability. In the present study we evaluated fecundity rate, ovarian follicular numbers, ova production, mitochondrial number, structure and function, and cytoplasmic lamellae (CL) in young (2–4 months) and old (12–18 months) Syrian hamsters (Mesocricetus auratus). Young hamsters had higher fertilisation rates and larger litters than old hamsters (100 vs 50% and 9.3 ± 0.6 vs 5.5 ± 0.6, respectively). Ovarian tissue from superovulated animals showed a 46% decrease in preantral follicles in old versus young hamsters. There was a 39% reduction in MII oocyte number in old versus young hamsters. Young ova had no collapsed CL, whereas old ova were replete with areas of collapsed, non-luminal CL. Eighty-nine per cent of young ova were expanded against the zona pellucida with a clear indentation at the polar body, compared with 58.64% for old ova; the remaining old ova had increased perivitelline space with no polar body indentation. Higher reactive oxygen species levels and lower mitochondrial membrane potentials were seen in ova from old versus young hamsters. A significant decrease in mitochondrial number (36%) and lower frequency of clear mitochondria (31%) were observed in MII oocytes from old versus young hamster. In conclusion, the results of the present study support the theory of oocyte depletion during mammalian aging, and suggest that morphological changes of mitochondria and CL in oocytes may be contributing factors in the age-related decline in fertility rates.

Context:Hip and pelvic injuries are often associated with direct trauma, but spe-cific fractures to the acetabulum are rare. The signs and symptoms of an acetabular fracture can mimic those of conditions that are more common at the hip area, and therefore the specificity of the diagnostic testing is crucial.Objective:To present the case of a female Division I college field-hockey player who developed a superomedial acetabular fracture.Background:The athlete’s initial complaint of intolerable hip pain decreased after a 3-week rest period but persisted with passive internal and external hip rotation. Additional diagnostic testing was needed to differentiate the various pathologies that were associated with her symptoms.Conclusions:Clinicians should be aware of the potential differential diagnoses of the hip and should investigate all potential possibilities even though they might not coincide with the initial injury.

Leukemia inhibitory factor (LIF) enhances in vitro murine preimplantation development in a time- and dose-dependent fashion. Knockout experiments have demonstrated that endometrial LIF is essential for in vivo murine implantation. We assessed the impact of LIF and an anti-LIF polyclonal antibody (pab) on in vivo development and developed a novel and successful nonsurgical method of embryo transfer for this species, a transcervical blastocyst transfer technique. The objectives of this study were to evaluate the effects of LIF and the anti-LIF pab on 1) implantation, resorption, pregnancy, and viability rates and 2) the overall structural and skeletal development. Two-cell embryos were recovered from superovulated mated donors, cultured to the expanded blastocyst stage, and transferred transcervically into pseudopregnant recipients. Exposure to 5000 U/ml LIF resulted in significant increases in implantation, pregnancy, and viability rates compared with controls. A similar dose of pab produced overall inhibitory effects with a significant decrease in implantation rate. Paradoxically, lower pab doses resulted in significantly increased viability rates. Exposure to LIF had no effect on fetoplacental development. However, pab treatments had variable but significant negative effects on placental length, ossification of the exoccipital bone, and vertebral space width compared with controls. Exposure of murine blastocysts to LIF at the time of transcervical transfer resulted in pronounced positive effects on implantation and pregnancy rates without affecting fetal development. A similar pab dose dramatically reduced implantation and pregnancy rates; at high and low doses, pab produced deleterious effects on placental and skeletal development.

Objective Recent results from the Multimodal Treatment Study of Attention-Deficit/Hyperactivity Disorder (ADHD; MTA) have demonstrated impairments in several functioning domains in adults with childhood ADHD. The childhood predictors of these adult functional outcomes are not adequately understood. The objective of the present study was to determine the effects of childhood demographic, clinical, and family factors on adult functional outcomes in individuals with and without childhood ADHD from the MTA cohort. Method Regressions were used to determine associations of childhood factors (age range 7–10 years) of family income, IQ, comorbidity (internalizing, externalizing, and total number of non-ADHD diagnoses), parenting styles, parental education, number of household members, parental marital problems, parent–child relationships, and ADHD symptom severity with adult outcomes (mean age 25 years) of occupational functioning, educational attainment, emotional functioning, sexual behavior, and justice involvement in participants with (n = 579) and without (n = 258) ADHD. Results Predictors of adult functional outcomes in ADHD included clinical factors such as baseline ADHD severity, IQ, and comorbidity; demographic factors such as family income, number of household members and parental education; and family factors such as parental monitoring and parental marital problems. Predictors of adult outcomes were generally comparable for children with and without ADHD. Conclusion Childhood ADHD symptoms, IQ, and household income levels are important predictors of adult functional outcomes. Management of these areas early on, through timely treatments for ADHD symptoms, and providing additional support to children with lower IQ and from households with low incomes, could assist in improving adult functioning.

Background In human oocytes, as in other mammalian ova, there is a significant variation in the pregnancy potential, with approximately 20% of oocyte-sperm meetings resulting in pregnancies. This frequency of successful fertilization decreases as the oocytes age. This low proportion of fruitful couplings appears to be influenced by changes in mitochondrial structure and function. In this study, we have examined mitochondrial biogenesis in both hamster (Mesocricetus auratus) and mouse (Mus musculus) ova as models for understanding the effects of aging on mitochondrial structure and energy production within the mammalian oocyte. Methodology/Principal Findings Individual metaphase II oocytes from a total of 25 young and old mice and hamsters were collected from ovarian follicles after hormone stimulation and prepared for biochemical or structural analysis. Adenosine triphosphate levels and mitochondrial DNA number were determined within individual oocytes from young and old animals. In aged hamsters, oocyte adenosine triphosphate levels and mitochondrial DNA molecules were reduced 35.4% and 51.8%, respectively. Reductions of 38.4% and 44% in adenosine triphosphate and mitochondrial genomes, respectively, were also seen in aged mouse oocytes. Transmission electron microscopic (TEM) analysis showed that aged rodent oocytes had significant alterations in mitochondrial and cytoplasmic lamellae structure. Conclusions/Significance In both mice and hamsters, decreased adenosine triphosphate in aged oocytes is correlated with a similar decrease in mtDNA molecules and number of mitochondria. Mitochondria in mice and hamsters undergo significant morphological change with aging including mitochondrial vacuolization, cristae alterations, and changes in cytoplasmic lamellae.