The behavioral deficits and cognitive impairment are correlated with decreased IGF-II and ERK in depressed mice induced by chronic unpredictable stress.

AIM: To investigate the behavioral deficits, cognitive impairment and possible mechanisms induced by chronic unpredictable stress (CUS) in mice of different ages. METHODS: The behaviors and cognition were tested using the open field test, tail suspension test and the Morris water maze. The changes in the insulin-like growth factor II (IGF-II) and the extracellular signal-regulated kinase (ERK) and phosphorylation (p-ERK) in the hippocampus (HP) and prefrontal cortex (PFC) were evaluated by immunohistochemistry. RESULTS: The 15-month-old mice revealed a significant decline in spontaneous behavior and the learning-memory function and showed a decrease in IGF-II and p-ERK expression levels in HP and PFC. Four weeks of CUS exposure induced significant anxiety- and depression-like behavior and learning-memory function impairment in 3- to 15-month-old mice, and reduced IGF-II and p-ERK expression levels in HP and PFC, compared with control group mice, respectively. CONCLUSIONS: The behavioral deficits and cognitive impairment induced by CUS and aging in mice could be associated with the down-regulated expression of IGF-II and p-ERK in HP and PFC. This role seems to be dependent on the intracellular ERK pathway.

Inflammasomes-dependent regulation of IL-1ß secretion induced by the virulent Mycobacterium bovis Beijing strain in THP-1 macrophages.

Mycobacterium bovis is the causative agent of tuberculosis in cattle. Infection of macrophages with M. bovis leads to the activation of the "nucleotide binding and oligomerization, leucine-rich repeat and pyrin domains-containing protein 3" (NLRP3) and "absent in melanoma 2" (AIM2) inflammasomes, which in turn triggers release of the proinflammatory cytokine interleukin-1ß (IL-1ß) that contributes to bacterial clearance and plays a crucial role in the host defense. However, NLRP3 and AIM2 inflammasome activation is influenced by several factors and how IL-1ß secretion by M. bovis-infected macrophages is regulated via the inflammasome pathway remains unclear. Here we found that IL-1ß secretion and pro-IL-1ß protein accumulation were inhibited in THP-1 macrophages upon exposure to the virulent M. bovis Beijing strain in the presence of high K(+) concentrations, cycloheximide (a protein synthesis inhibitor) and PR-619 (a deubiquitinating enzyme inhibitor). Scavenging reactive oxygen species (ROS) induced by N-acetylcysteine reduced IL-1ß release independent of the mitochondrial permeability transition. Collectively, our results suggest that IL-1ß secretion by M. bovis-infected THP-1 macrophages is reduced by high extracellular K(+) concentration, inhibition of new protein synthesis, deubiquitination, and ROS generation.

Downregulation of ß-Soluble N-Ethylmaleimide-Sensitive Factor Attachment Protein: Proteomics-Based Identification in Early-Stage Prion Disease.

Prion diseases are known as neurodegenerative diseases of the central nervous system with a long incubation period. Alzheimer's disease (AD) and prion diseases share the hallmark of severe neuronal loss, although their pathogenic mechanisms are similarly incomplete. It appears that these two neurodegenerative diseases share a complex deterioration of function involved in the onset of neuronal loss. To investigate presymptomatic biochemical changes indicative of the initial stage of prion diseases and decipher the pathophysiological mechanisms of these two neurodegenerative diseases, we performed a differential proteomic analysis on brain tissues of 263K-infected hamsters during the presymptomatic period and transgenic APPSWE, PSEN1dE9 mice (a mouse model of AD). We identified 7 differentially expressed proteins including the ß-soluble N-ethylmaleimide-sensitive factor attachment protein (ß-SNAP) by 2-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The ß-SNAP expression patterns in the brains of cases and controls were further quantified by Western blotting. ß-SNAP showed an early decrease followed by a progressive depletion. The expression of ß-SNAP was also significantly downregulated in the mouse model of AD. ß-SNAP is brain-specific and known to bind to the SNAP receptors and is therefore involved in the control of neurotransmitter release as well as in constitutive vesicular transport. Our results suggest that presynaptic failure and abnormalities in neurotransmission may be early events in the development of neuronal dysfunction.

The diagnostic and prognostic role of miR-27a in cancer.

MicroRNA-27a (miR-27a) has been reported to be abnormally expressed in patients with cancer, and it could play potential roles as a diagnostic and prognostic biomarker of cancers. However, the diagnostic and prognostic role remains unclear. Hence, this meta-analysis, based on published data, was conducted to assess the utility of miR-27a as a diagnostic and prognostic marker in various cancers. To identify eligible studies, databases: Web of Science, PubMed, and CNKI were searched, with 868 literatures obtained, 16 of which were included in the Meta-analysis. The pooled results of studies conducted with serum/plasma showed that miR-27a was a valuable diagnostic biomarker in cancers (area under curve (AUC)= 0.91, sensitivity (SEN)= 0.84, specificity (SPE)= 0.85), with the diagnostic value slightly reduced in tumor tissue samples (AUC=0.83, SEN=0.78, SPE: 0.74). Additionally, the pooled results revealed that high expression of miR-27a predicted poor prognosis of cancer in serum/plasma (hazard ratio (HR) = 0.63, PHeterogeneity = 0.278, I2= 21.50%) but not in tumor tissue (HR = 0.98, PHeterogeneity =0.577, I2= 0.0). In brief, our results suggested that miR-27a in serum/plasma or tumor tissue could act as a diagnostic biomarker, and that miR-27a in serum/plasma could predict cancer patients' survival.

A Case of Solitary Peutz-Jeghers Syndrome Leading to Chronic Small Bowel Obstruction Due to Intussusception From a Large Hamartomatous Polyp.

We report a case of a 33-year-old male who presented to the emergency department with a three-day history of severe diffuse abdominal pain associated with anorexia, nausea, and vomiting. Computed tomography (CT) imaging of the abdomen and pelvis revealed a long segment of intussusception in the proximal jejunum and a round lesion along the intussusception with punctate hyperdensities. The patient underwent a diagnostic laparoscopy converted to open small bowel resection and end-to-end anastomosis that demonstrated a pedunculated jejunal mass. The mass was removed, and the pathology revealed a hamartomatous polyp with features of Peutz-Jeghers syndrome (PJS). The patient did not have a family history, previous endoscopic findings, or physical exam findings such as mucocutaneous pigmentation that could be attributed to PJS.  Definitive diagnosis of solitary PJS-type hamartomatous polyps depends on histopathological findings. Genetic analysis for mutations of the PJS susceptible gene, STK11/LB1 located at 19p13.3, as well as loss of heterozygosity at that locus, have been used for the diagnosis of PJS. In patients with large pedunculated hamartomatous polyps, chronic intussusception can occur. If pathology reveals features of Peutz-Jeghers, but the patient lacks the characteristic mucocutaneous pigmentation, family history of PJS, or additional polyps within the GI tract, then solitary PJS may be suspected.

The Diagnostic and Prognostic Value of miR-155 in Cancers: An Updated Meta-analysis.

BACKGROUND: MicroRNA-155 has been discussed as a biomarker in cancer diagnosis and prognosis. Although relevant studies have been published, the role of microRNA-155 remains uncertain because of insufficient data. METHODS: We conducted a literature search in PubMed, Embase, and Web of Science databases to obtain relevant articles and extract data to evaluate the role of microRNA-155 in cancer diagnosis and prognosis. RESULTS: The pooled results showed that microRNA-155 presented a remarkable diagnostic value in cancers (area under the curve = 0.90, 95% confidence interval (CI 0.87-0.92; sensitivity = 0.83, 95% CI 0.79-0.87; specificity = 0.83, 95% CI 0.80-0.86), which was maintained in the subgroups stratified by ethnicity (Asian and Caucasian), cancer types (breast cancer, lung cancer, hepatocellular carcinoma, leukemia, and pancreatic ductal adenocarcinoma), sample types (plasma, serum, tissue), and sample size (n >100 and n <100). In prognosis, a combined hazard ratio (HR) showed that microRNA-155 was significantly associated with poor overall survival (HR = 1.38, 95% CI 1.25-1.54) and recurrence-free survival (HR = 2.13, 95% CI 1.65-2.76), and was boundary significant with poor progression-free survival (HR = 1.20, 95% CI 1.00-1.44), but not significant with disease-free survival (HR = 1.14, 95% CI 0.70-1.85). Subgroup analyses in overall survival showed that microRNA-155 was associated with poor overall survival in the subgroups stratified by ethnicity and sample size. However, the significant association was maintained in cancer types subgroups of leukemia, lung cancer, and oral squamous cell carcinoma, but not in colorectal cancer, hepatocellular carcinoma, and breast cancer, and was maintained in sample types subgroups of bone marrow and tissue, but not in plasma and serum. CONCLUSIONS: Results from this meta-analysis demonstrated that microRNA-155 was a valuable biomarker in cancer diagnosis and prognosis.

Small Bowel Follow-Through: Treatment for Small Bowel Obstruction or Delaying the Inevitable?

BACKGROUND: Over 400,000 patients are admitted annually for small bowel obstruction (SBO), of which 20-40% require operative intervention, representing more than 2.3 billion dollars in healthcare expenses. Recurrence of SBO increases with a longer duration of follow-up with up to 15-20% recurrence rates within a five-year period. Small bowel follow-through (SBFT) consisting of serial X-rays with oral contrast has been shown to decrease overall length of stay (LOS) in patients with adhesive SBO. The aim of this study is to determine if SBFT administered to patients with SBO decreases 30-day and up to five-year readmission rates secondary to recurrent SBO. METHODS: The institutional review board (IRB) approved a single institution retrospective study from 2010 to 2020 that included a total of 742 patients. These patients were organized into groups of those who received the SBFT <24 hours after admission (n=40), those who received the SBFT >24 hours (n=198), and the third group of patients who did not receive the SBFT (n=658). Readmission rates <30 days, 70 years along with BMI <25, 25-29.9, 30-34.9, 35-39.9, >40, as well as the number of intraabdominal surgeries, gender, and need for operative intervention during the admission were evaluated to assess for any associations with recurrence. Readmission within 30 days and up to five years were compared. RESULTS: There were no significant differences in recurrence rates between groups with SBFT <24 hours (p=0.338) or SBFT >24 hours (p=0.889) when compared to the no SBFT group. There was nearly a 48% chance of readmission for another episode of an SBO for patients who did not undergo an operative intervention. While patients who underwent operative intervention had around a 29% chance of having a subsequent episode of an SBO. This is consistent with a statistically significant decrease in one-year (p=0.027) recurrences in patients who underwent operative intervention. CONCLUSION: There was no significant difference in recurrences with gender, most BMI groups, or in groups who underwent an SBFT. Operative intervention is associated with a statistically significant decrease in recurrence rates of SBO within one year of presentation.

Effectiveness of brief mindfulness intervention for college students' problematic smartphone use: The mediating role of self-control.

BACKGROUND: Mainland China has the most smartphone users worldwide, especially among college students, while mindfulness intervention can significantly alleviate the level of problematic smartphone use. We examined the effects of a brief mindfulness intervention on problematic smartphone use and investigated if this effect is mediated by self-control. METHODS: Participants were recruited randomly from a university in Beijing of China. Forty-four college students were assigned to a mindfulness group or a control group. The mindfulness group took part in a brief (30 min) single-session mindfulness intervention. The control group was instructed to listen to a neutral news audio recording for the same duration (30 min). The Freiburg Mindfulness Inventory, Mobile Phone Addiction Tendency Scale, and Self-control Scale were used to measure state mindfulness, problematic smartphone use, and self-control of college students at pre-intervention and post-intervention, respectively. RESULTS: Two-way repeated-measures ANOVA revealed that the mindfulness group had significant improvements in state mindfulness (p = .049) and self-control (p = .012), and had significant alleviation in problematic smartphone use (p < .001) at post-intervention. In the regression model, self-control had a mediating effect between mindfulness intervention and problematic smartphone use (95% CI [0.490, 7.216]). CONCLUSIONS: A brief single-session mindfulness intervention can alleviate the level of problematic smartphone use and increase the level of state mindfulness and self-control compared to the control group. Self-control can completely mediate the efficacy of the mindfulness intervention in reducing problematic smartphone use.

The diagnostic and prognostic value of the miR-17-92 cluster in hepatocellular carcinoma: A meta-analysis.

Previous studies demonstrated that microRNAs (miRNAs) could serve as biomarkers in various cancers. This meta-analysis aimed to determine the roles of a miR-17-92 cluster in hepatocellular carcinoma (HCC). Here, eligible included studies were searched through PubMed, Embase, and Wan Fang databases up to 1st February 2022. Relevant data were extracted from each eligible study to evaluate the relationship between miRNA-17-92 cluster miRNA expression and the diagnosis and prognosis of HCC. Finally, a total of 21 studies were pooled and included in the meta-analysis, of which four articles were used for diagnostic meta-analysis and eight articles were used for prognostic meta-analysis. The pooled sensitivity, specificity, and diagnostic odds ratios (DOR) of the miR17-92 cluster for diagnosis of HCC were 0.75 [95% confidence interval (CI): 0.64-0.83], 0.73 (95% CI: 0.65-0.79), and 7.87 (95% CI: 5.36-11.54), respectively. Also, the area under the curve (AUC) for the miR-17-92 cluster when diagnosing HCC was 0.79 (95% CI: 0.76-0.83). For prognostic analysis, hazard ratios (HRs) with 95% CIs were extracted from the included studies and pooled HRs were determined to assess the associations. Patients with increased expression of miR17-92 cluster miRNA were associated with poor overall survival (OS) and recurrence-free survival (RFS) (HR=1.86, 95% CI: 1.04-3.33; HR = 4.18, 95% CI: 3.02-5.77, respectively), but not progression-free survival (PFS) (HR = 0.43, 95% CI: 0.25-0.73), while no association of the miR-17-92 cluster high-expression was detected with disease-free survival (DFS) (HR: 0.95, 95% CI: 0.21-4.34). In short, current pieces of evidence suggested that the miR-17-92 cluster may serve as a novel diagnostic and prognostic biomarker for HCC. However, given the limited study number, larger-size, multi-center, and higher-quality studies are indispensable in the future.

Effects of CYP2C19 genetic polymorphisms on the cure rates of H. pylori in patients treated with the proton pump inhibitors: An updated meta-analysis.

Background: The cure rates of Helicobacter pylori (H. pylori) treatment using a proton pump inhibitor (PPI) are gradually decreasing due to antibiotic resistance, poor compliance, high gastric acidity, and cytochrome P450 2C19 (CYP2C19) polymorphism, and the effects of PPI depend on metabolic enzymes, cytochrome P450 enzymes. The aim of this meta-analysis was to determine whether CYP2C19 polymorphisms affect H. pylori cure rates in patients treated with different proton pump inhibitors (PPIs) according to stratified analysis. Materials and methods: The literature was searched with the key words "H. pylori" and "CYP2C19" in PubMed, CNKI, and Wanfang up to 31 May 2022, and the studies were limited to clinical observational or randomized controlled trials (RCTs). Finally, seven RCTs and 29 clinical observational studies met the inclusion criteria and were used for the meta-analysis via STATA version 16. Results: The cure rates were significantly different between genotypes of homozygous extensive metabolizers (EM) and poor metabolizers (PM) (OR = 0.58, 95% CI: 0.47-0.71) and between EM and heterozygous extensive metabolizers (IM) (OR = 0.71, 95% CI: 0.59-0.86), but not between IM and PM. Moreover, there was a significantly lower H. pylori cure rate in EM subjects than that in IM subjects when treated with omeprazole (66.4% vs. 84.1%), lansoprazole (76.1% vs. 85.6%), but not rabeprazole, esomeprazole, or pantoprazole. In addition, there was a significantly lower H. pylori cure rate in EM subjects than that in IM subjects when treated with a PPIs for 7 days (77.4% vs. 82.1%), but not 14 days (85.4% vs. 90.0%). Conclusion: Carriers of CYP2C19 loss-of-function variant alleles (IM and PM) exhibit a significantly greater cure rate of H. pylori than noncarriers (EM) regardless of other factors (84.7% vs. 79.2%). In addition, pantoprazole- and rabeprazole-based quadruple therapy for H. pylori treatment is less dependent on the CYP2C19 genotype and should be prioritized in Asian populations with H. pylori.

Hemagglutinating virus of Japan envelope (HVJ-E) can enhance the immune responses of swine immunized with killed PRRSV vaccine.

Porcine reproductive and respiratory syndrome virus (PRRSV) is an economically detrimental pig pathogen that causes significant losses for the pig industry. The immunostimulatory effects of hemagglutinating virus of Japan envelope (HVJ-E) in cancer therapy and the adjuvant efficacy of HVJ-E have been previously evaluated. The objective of this study was to investigate the adjuvant effects of HVJ-E on immunization with killed PRRSV vaccine, and to evaluate the protective effects of this immunization strategy against virulent PRRSV infection in piglets. Next, the PRRSV-specific antibody response, lymphocyte proliferation, PRRSV-specific IL-2, IL-10 and IFN-γ production, and the overall protection efficacy were evaluated to assess the immune responses of the piglets. The results showed that the piglets inoculated simultaneously with killed PRRSV vaccine and HVJ-E had a significantly stronger immune response than those inoculated with killed PRRSV vaccine alone. Our results suggest that HVJ-E could be employed as an effective adjuvant to enhance the humoral and cellular responses of piglets to PRRSV.

Examining the Effects of Brief Mindfulness Training on Athletes' Flow: The Mediating Role of Resilience.

BACKGROUND: Flow is characterized by the strong concentration in competitions, eliminating irrelevant thoughts and emotions, integrating all tasks, and continuing the competition smoothly even in challenging situations. The present study was into whether or not brief mindfulness training can improve athletes' flow and further explore the mediating effect of resilience in the intervention. METHODS: The 2 (experimental conditions) × 2 (time) mixed design was used in this study. Fifty-seven student-athletes were recruited and randomly assigned into either a brief mindfulness group (n = 29) or a control group (n = 28). Before and after the intervention, every participant completed a self-report measure including mindfulness, flow, and resilience. RESULTS: Participants in the brief mindfulness group showed increased mindfulness, flow, and resilience (p < 0.001) after brief mindfulness training; when putting resilience change (B = 0.30, 95% CI [0.031, 0.564]) into the equation, the direct (95% CI [3.156, 13.583]) and indirect (95% CI [0.470, 5.048]) effects of mindfulness training were both significant. CONCLUSION: It was concluded that brief mindfulness training could significantly improve athletes' flow and resilience, and resilience partly mediated the effects of brief mindfulness training on flow.

Early Use of Small Bowel Follow Through Reduces Stay and Cost in Small Bowel Obstructions.

Background According to the Nationwide Inpatient Sample in 2011, nearly 1,500,000 admissions with over 300,000 laparotomies were performed for adhesion-related small bowel obstructions (SBOs). Small bowel follow through (SBFT) consists of serial X-rays with oral Gastrografin contrast that can diagnose obstructions requiring operative intervention. Furthermore, the contrast has a therapeutic osmotic effect which may promote transit and resolve an SBO. The aim of the study was to determine if early SBFT administration to patients with SBO decreases length of stay (LOS), hospital costs, and can identify patients who will fail non-operative management (NOM). Methodology This is a single institution retrospective study conducted from 2010 to 2019 with a total of 476 patients. We divided patients into three groups: SBFT within <24 hours of admission (n = 40), SBFT >24 hours after admission (n = 198), and did not receive SBFT (n = 238). We compared the overall LOS, hospital costs, and time from SBFT to the operating room using an analysis of variance. Results LOS significantly differed between groups with SBFT within ≤24 hours having an average LOS of 6.95 days compared to 10.65 days in the SBFT after >24 hours and 11.75 days in the no SBFT group (p = 0.005). Median time to the operating room in patients receiving SBFT was one day, which was significantly shorter than a median time of four days for no SBFT group (p = <0.05). Decreased LOS by 4.8 days equated to saving $8,657 per patient. Conclusions SBFT administered within 24 hours decreases LOS, overall costs, and time to operating room in patients who fail NOM.

Genetic Variation of Inflammatory Genes to Ischemic Stroke Risk in a Chinese Han Population.

BACKGROUND: Inflammation proteins play an important role in stroke occurrence. IL1A, IL1B, PTGS2, MMP2, and MMP9 were the mediators involved in the immune response, and the association of these genetic variations with ischemic stroke (IS) risk was still unclear. METHODS: To investigate the susceptibility of genetic variations of IL1A, IL1B, PTGS2, MMP2, and MMP9 to IS risk, we performed a case-control study involving 299 patients and 300 controls in a Chinese population. Thirteen genetic variations of investigated genes of all participants were genotyped using an improved multiplex ligase detection-reaction technique. RESULTS: No SNP in all genes showed an association with overall IS. However, in subgroup analysis, PTGS2 rs689466 (dominant model: CT vs TT - ORadjusted= 2.51, 95% CI: 1.22-5.16, p = 0.012; co-dominant model: CT/CC vs TT - ORadjusted= 2.53, 95% CI: 1.26-5.07, p = 0.009; additive model - ORadjusted= 2.26, 95% CI: 1.19-4.28, p = 0.013) and rs5275 (dominant model: GG vs AA - ORadjusted= 0.31, 95% CI: 0.12-0.80, p = 0.016; co-dominant model: GA/GG vs AA - ORadjusted= 0.45, 95% CI: 0.21-0.95, p = 0.036; additive model - ORadjusted= 0.60, 95% CI: 0.39-0.92, p = 0.020) were associated with IS type of small-vessel occlusion. CONCLUSION: Our study suggested that PTGS2 rs689466 C and rs5275 A were potentially associated with IS subtype of small-vessel occlusion. Our result should be confirmed with further large sample sized studies.

Comparison between core needle biopsy and excisional biopsy for breast neoplasm.

ABSTRACT: This study aimed to explore clinical significance of core needle biopsy (CNB) in pathological diagnosis of breast neoplasm.Seventy one breast neoplasm samples were obtained from Tongzhou Maternal and Child Health Hospital of Beijing between the years of 2006 and 2014. Forty five specimens were obtained via CNB and cases offering 26 of them received neoadjuvant chemotherapy. Pathology, histology, and immunohistochemistry results were compared between CNB specimens and excisional biopsy.Upward and downward tendencies could be observed in CNB specimens and excisional biopsy, respectively, in all items. Tumor proportion of CNB tissues was (33 + 2)/45 = 77.78%, when ductal carcinoma in situ detected by both CNB and excisional biopsy was 31/45 = 68.89%, with a consistency of (31 + 3)/45 = 75.56%. Tumor thrombus detected by both CNB and excisional biopsy was 2/45 = 4.44%. Among cases receiving neoadjuvant chemotherapy, CNB and excisional biopsy, in mitotic figure, cytological scoring and histological grading, showed a total change rate of >50% (50%-75%), while changes in duct and cellular heteromorphism were not distinct. Cases showing changes were up to 73.08%, with 8/26 = 30.77% for rise and 11/26 = 42.31% for descent.CNB could be used for preoperative diagnosis of breast neoplasm, and help to determine proper treatment regimen, thus elevating the rate of breast conserving. However, this method still has several limitations, particularly in immunohistochemical tests of human epidermal receptor protein-2. Neoadjuvant chemotherapy may influence the accuracy of CNB diagnosis.

Cellular prion protein released on exosomes from macrophages binds to Hsp70.

Prion diseases are infectious and fatal neurodegenerative disorders. The cellular prion protein (PrP(C)) converting into misfolded isoform of prion protein (PrP(Sc)) is responsible for prion disease infection. Immune system plays an important role in facilitating the spread of prion infections from the periphery to the central nervous system. Macrophages were considered associated with the transportation and replication of PrP(Sc). So, understanding the PrP(C) trafficking in macrophages is important to explore the transport mechanism for PrP(Sc). Here, we isolated exosomes from the culture medium of Ana-1 macrophage cell line and investigated the PrP(C) trafficked by exosomes and the interaction of PrP(C) with Hsp70 in secreted exosomes by western blotting, immunoelectron microscopy, and co-immunoprecipitation. The results showed that the isolated vesicles from the culture medium of macrophages were characterized by exosomes and bore PrP(C). And PrP(C) bound to Hsp70 both in intracellular environment and secreted exosomes. In contrast, PrP(C) had no interaction with marker proteins of exosomes, Tag101 and Flotillin-1. These results suggested that PrP(C) present in extracellular space might be externalized through secreted exosomes from macrophages, and Hsp70 may play roles in the process of PrP(C) released via secreted exosomes.

Sports experts' unique perception of time duration based on the processing principle of an integrated model of timing.

BACKGROUND: Duration perception is an essential part of our cognitive and behavioral system, helping us interact with the outside world. An integrated model of timing, which states that the perceived duration of a given stimulus is based on the efficiency of information extraction, was recently set forth to improve current understanding of the representation and judgment of time. However, the prediction from this model that more efficient information extraction results in longer perceived duration has not been tested. Thus, the aim of this study is to investigate whether sports experts, as a group of individuals with information extraction superiority in situations relevant to their sport skill, have longer duration perceptions when they view expertise-related stimuli compared with others with no expertise/experience. METHODS: For this study, 81 subjects were recruited based on a prior power analysis. The sports experts group had 27 athletes with years of professional training in diving; a wrestler group and a nonathlete group, with each of these groups having 27 subjects, were used as controls. All participants completed a classic duration reproduction task for subsecond and suprasecond durations with both the diving images and general images involved. RESULTS: The divers reproduced longer durations for diving stimuli compared with general stimuli under both subsecond and suprasecond time ranges, while the other samples showed the opposite pattern. Furthermore, the years of training in diving were positively correlated with the magnitude of the prolonged reproduction duration when divers viewed diving stimuli. Moreover, the diver group showed a more precise duration perception in subsecond time range for general stimuli compared with the wrestlers and nonathletes. CONCLUSION: The results suggest that sports experts perceive longer duration when viewing expertise-related stimuli compared with others with no expertise/experience.

Single-Cell-Derived Primary Rectal Carcinoma Cell Lines Reflect Intratumor Heterogeneity Associated with Treatment Response.

PURPOSE: The standard treatment of patients with locally advanced rectal cancer consists of preoperative chemoradiotherapy (CRT) followed by surgery. However, the response of individual tumors to CRT is extremely diverse, presenting a clinical dilemma. This broad variability in treatment response is likely attributable to intratumor heterogeneity (ITH). EXPERIMENTAL DESIGN: We addressed the impact of ITH on response to CRT by establishing single-cell-derived cell lines (SCDCL) from a treatment-naïve rectal cancer biopsy after xenografting. RESULTS: Individual SCDCLs derived from the same tumor responded profoundly different to CRT in vitro. Clonal reconstruction of the tumor and derived cell lines based on whole-exome sequencing revealed nine separate clusters with distinct proportions in the SCDCLs. Missense mutations in SV2A and ZWINT were clonal in the resistant SCDCL, but not detected in the sensitive SCDCL. Single-cell genetic analysis by multiplex FISH revealed the expansion of a clone with a loss of PIK3CA in the resistant SCDCL. Gene expression profiling by tRNA-sequencing identified the activation of the Wnt, Akt, and Hedgehog signaling pathways in the resistant SCDCLs. Wnt pathway activation in the resistant SCDCLs was confirmed using a reporter assay. CONCLUSIONS: Our model system of patient-derived SCDCLs provides evidence for the critical role of ITH for treatment response in patients with rectal cancer and shows that distinct genetic aberration profiles are associated with treatment response. We identified specific pathways as the molecular basis of treatment response of individual clones, which could be targeted in resistant subclones of a heterogenous tumor.

Enhanced susceptibility to chemical induction of ovarian tumors in mice with a germ line p53 mutation.

Mice with a germ line p53 mutation (p53(Ala135Val/wt)) display increased susceptibility to lung, skin, and colon carcinogenesis. Here, we show that p53(Ala135Val/wt) mice developed ovarian tumors significantly more rapidly than their wild-type littermates after 7,12-dimethylbenz(a)anthracene (DMBA) treatment. Approximately 50% of the ovarian tumors in p53(wt/wt) mice and 23% in p53(Ala135Val/wt) mice are adenocarcinomas and the remaining tumors were adenocarcinoma mixed with sarcoma or ovarian sarcomas. All of the p53(Ala135Val/wt) mice had died of ovarian tumors 25 weeks after the initial DMBA treatment, whereas >50% of p53(wt/wt) mice were still alive. These mice not only have a shortened tumor latency but also closely resemble a subset of human ovarian tumors containing the p53 mutation. Microarray and GenMAPP analyses revealed that the mutant p53 (Ala135Val) affected several cellular processes, including the cell cycle, apoptosis, and Wnt pathways. These findings indicate that a germ line p53 mutation significantly enhanced DMBA-induced ovarian tumor development and progression.

Fine mapping and candidate gene analyses of pulmonary adenoma resistance 1, a major genetic determinant of mouse lung adenoma resistance.

Pulmonary adenoma resistance 1 (Par1) is a major genetic determinant of mouse lung adenoma resistance. Although Par1 was previously mapped to mouse chromosome 11 by conventional linkage analyses, its candidate region was broad and undefined. In our present study, we generated Par1 congenic mice using two mouse strains A/J (Par1/-) and Mus spretus (Par1/+). Analyzing these congenic mice enabled us to fine map the Par1 quantitative trait loci (QTL) into a 2.0-cM (2.2 Mb) chromosomal region between genetic marker D11Mit70 and the gene Hoxb9. We then conducted systematic candidate gene screening through nucleotide polymorphism and expression analyses. Genes showing differential lung tissue expression or carrying nonsynonymous single nucleotide polymorphisms were identified and discussed. In particular, we evaluated tumor suppressor gene Tob1 for its Par1 candidacy. Our findings have narrowed the Par1 QTL region and will greatly facilitate the identification of the major genetic determinant of mouse lung adenoma resistance.