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Various functions for improving automobile seat comfort have been developed to reduce driver stress. However, how drivers respond to the seat comfort functions in real driving has not yet been studied. This experiment evaluated the effect of a seat air-conditioning system (ACS) on driver stress by tracking changes in various bio-signals during 60-min highway driving. Heart rate, heart rate variability, skin conductance, and respiration rates were quantified using non-invasive sensors from 13 drivers while varying the seat ACS condition in hot weather. Study results show that the high-frequency power of the heart rate variability, mean skin conductance level, and mean respiration rate detected the changes in the seat ACS over 60%, implying the possibility of seat comfort monitoring using the bio-signals. Further research should be conducted with various environmental or driver conditions to improve detection performance.

Monitoring driver thermal stress is an integral step for developing an automated climate control function. In this experimental study, various physiological measures for driver’s thermal stress were tracked while intentionally by altering thermal conditions of the seat with a seat air conditioning system (ACS) in summer and a seat heating system (HS) in winter. It was aimed to determine reliable physiological measures for identifying the changes in thermal status induced by the two seat climate control systems. In the first experiment, twenty experienced drivers drove a comfortable sedan for 60 minutes on a real highway while varying the intensity of the seat ACS every 10 minutes to incur ‘hot’ – ‘cool’ – ‘hot’ – ‘cool’ thermal stress. In the second experiment, a new group of eighteen drivers drove the same highway for 30 minutes while increasing the intensity of seat HS to incur ‘cold’ to ‘warm’ thermal stress. Their thermal stress status has been evaluated by heart rate variability (HRV), skin conductance (SC) level, heart rate (HR), and respiration (RES) rate, as well as subjective discomfort ratings during driving. The reliability of each physiological measure was determined by detection rate, which indicated the ratio of occurrences that the physiological measure followed the changes in thermal conditions. The thermal change by seat ACS was detected over 60% by the high-frequency power of HRV, mean SC level, and RES rate. Changes in the thermal stress by seat HS were detected over 60% by the low-frequency power of HRV and RES rate. The findings of this study suggest that monitoring the driver’s HRV and RES rate may enable the vehicle to detect the changes in the driver’s thermal stress reliably.

Prolonged smartphone use induces passive stretch of neck tissues and muscle fatigue, affecting spinal stability and pain. It is necessary to evaluate the effect of smartphone use on the reflexive response to detect the changes in neck tissues and head stability. A laboratory experiment (n=10) was conducted to investigate the reflexive response of neck muscle to perturbation after 30 minutes of smartphone use. Neck extensor muscle activation and its activation timing to perturbation were investigated before and after smartphone use. Head angle and muscle activation level were collected during smartphone use. During smartphone use, muscle activation gradually increased. After smartphone use, neck muscles showed a higher activation level and significantly delayed onset to perturbation. Smartphone use changed the reflexive response of the neck muscle. Further study is needed to investigate the association between smartphone use and neuromuscular changes to the tissues of the cervical spine.

Crowdsourced financial information platforms often allow content contributors to publish equity research anonymously. This study examines whether investors value or discount information in anonymous equity research. In the short window around research releases, we find that investors’ stock price reaction to anonymous research is muted in comparison to nonanonymous research. Consistent with credibility concerns influencing investor response, we document that this discount to anonymous research dissipates as the monitoring of content contributors intensifies and as authors develop a reputation for high‐quality reporting. In addition, we perform a content analysis on the research reports and find that the muted market reaction to anonymous equity research is robust to controlling for textual attributes of information content, further supporting our inference that investors’ are concerned about the credibility of anonymous equity research.

We explore the role of investor relations (IR) in debt markets. Using earnings announcements as a laboratory, we examine whether, when, and to what extent IR departments help credit investors assimilate information. We find that the presence of IR decreases (increases) the negative (positive) impact on CDS spreads stemming from bad (good) earnings news, suggesting that IR efforts improve information precision and reduce transparency risk. Cross-sectional analyses suggest that IR matters more when uncertainty is high and creditors are concerned about the credit risk implications of firm performance. We also find that IR firms receive higher credit ratings and fewer covenants when issuing bonds, and CDS markets react less negatively when IR firms' bond ratings are downgraded below investment grade. Because firms choose their IR activities, we show that our inferences are robust to multiple methods of addressing endogeneity. Overall, we find that IR departments are influential in debt markets.

While reperfusion of autologous blood using the Cellsaver (CS) device is routine in cardiothoracic surgery, there is a paucity of evidence-based literature regarding its use in trauma. Utility of CS was compared in these two distinct populations at a Level 1 trauma center from 2017 to 2022. CS was successfully used in 97% and 74% of cardiac and trauma cases, respectively. The proportion of blood requirements provided by CS, compared to allogenic transfusion, was also significantly higher in cardiac surgery. However, there was still net benefit for CS in trauma surgery, with median salvaged transfusion volume of one unit, in both general & orthopedic trauma. Therefore, in centers where the cost of setting up CS, both in terms of equipment and personnel, is less than the cost of one unit of blood from blood bank, use of CS in trauma operations should be considered.

Current organoid models are limited by their inability to mimic mature organ architecture and associated tissue microenvironments1,2. Here we create multilayer bladder ‘assembloids’ by reconstituting tissue stem cells with stromal components to represent an organized architecture with an epithelium surrounding stroma and an outer muscle layer. These assembloids exhibit characteristics of mature adult bladders in cell composition and gene expression at the single-cell transcriptome level, and recapitulate in vivo tissue dynamics of regenerative responses to injury. We also develop malignant counterpart tumour assembloids to recapitulate the in vivo pathophysiological features of urothelial carcinoma. Using the genetically manipulated tumour-assembloid platform, we identify tumoural FOXA1, induced by stromal bone morphogenetic protein (BMP), as a master pioneer factor that drives enhancer reprogramming for the determination of tumour phenotype, suggesting the importance of the FOXA1–BMP–hedgehog signalling feedback axis between tumour and stroma in the control of tumour plasticity. Multilayer 3D reconstitution of bladder stem cells with stromal cells enables recapitulation of the architecture and molecular functions of bladder tissue.

An increase in pedestrian accidents associated with smartphone use has been one of the main issues in road traffic safety research and administration. Recently, traffic lights and safety signs embedded in the ground have been introduced, but without sufficient scientific consideration. A laboratory experiment evaluated the visibility of an in-ground signal while varying its contrast and position. Twenty-three participants performed a signal detection task when conducting texting while walking on a treadmill. The signals were displayed randomly onto the ground one at a time at three different positions with three different contrasts levels and moved towards a participant. In results, the approaching signals were detected 1.7 m ~ 2.9 m in front of participants, and there were significant differences in the visibility between contrast levels and positions (p

STUDY DESIGN Within-subject design of an experimental study. OBJECTIVE The aim of this study was to determine the effects of smartphone use on the activity level of the lumbar erector spinae muscles and spine kinematics during walking. SUMMARY OF BACKGROUND DATA Using a smartphone while walking makes the user hold the phone steady and look downward to interact with the phone. Walking with this non-natural posture of the head and the arms may alter the spine kinematics and increase the muscular load on the low back extensor muscles. METHODS Twenty healthy young individuals participated in the laboratory experiment. Each participant walked on a treadmill in five different conditions: normal walking without using a phone, conducting one-handed browsing while walking, two-handed texting while walking, walking with one arm bound, and walking with both arms bound. Spine kinematics variables and the myoelectric activity levels of the lumbar erector spinae muscles were quantified and compared between the five walking conditions. RESULTS Participants walked with significantly (P

Walking while distracted by a smartphone has been a major safety concern for pedestrians. Visual and cognitive attention paid to the smartphone while walking with the head tilted downward would affect the ability to perceive walkway hazards and elevate risks for pedestrian accidents associated with physical contact with obstacles. A laboratory experiment was conducted to evaluate the performance of detecting ground-level visual cues during texting while walking. Forty young smartphone users performed walking trials at faster, preferred, and slower speeds for the dual-task walking on a treadmill and detected approaching cues of three contrast levels. Detection distance was quantified from the location of cue detection to the participants to assess the effects of walking speed and cue contrast on detection performance. Results show that detection distance varied from 1.7 m to 2.9 m for Low to High contrast cues and from 2.3 m to 2.5 m for Slower to Faster walking speeds, and the effects of contrast and speed were statistically significant (p 0.05). Study findings suggest that higher contrast fixtures or in-ground signals and slower walking would help smartphone users perceive walkway hazards and in-ground safety signals earlier during their distracted walking.

Concurrent use of a smartphone while walking may influence low back muscle activation patterns due to restricted arm motions, limited trunk rotation and walking with the head in a flexed position. The objective of this study was to quantitatively determine the effects of smartphone use while walking on the level of myoelectric activity of the low back extensor muscles. Fifteen asymptomatic young smartphone users who were familiar with smartphone use while walking participated in this experiment. The electromyography (EMG) of the lumbar erector spinae muscles were collected bilaterally when they were conducting three walking tasks on a treadmill: 1) walking without smartphone use (upright walking); 2) web-browsing while walking; and, 3) texting while walking. Results found that the normalized EMG of the lumbar erector spinae muscles were significantly (p

Sm-p80, the large subunit of Schistosoma mansoni calpain, is a leading candidate for a schistosomiasis vaccine. The prophylactic and antifecundity efficacy of Sm-p80 has been tested in three animal models (mouse, hamster and baboon) using a multitude of vaccine formulations and approaches. In our continual effort to enhance the vaccine efficacy, in this study, we have utilized the adjuvant, synthetic hexa-acylated lipid A derivative, glucopyranosyl lipid A (GLA) formulated in aluminum (GLA-Alum) with recombinant Sm-p80. The rSm-p80+GLA-Alum immunization regimen provided 33.33%–53.13% reduction in worm burden in the mouse model and 38% worm burden reduction in vaccinated baboons. Robust Sm-p80-specific immunoglobulin (Ig)G, IgG1, IgG2a and IgM responses were observed in all immunized animals. The rSm-p80+GLA-Alum coadministration induced a mix of T-helper (Th) cells (Th1, Th2 and Th17) responses as determined via the release of interleukin (IL)-2, IL-4, IL-18, IL-21, IL-22 and interferon-γ.

Manual pushing or pulling with a hand tool is a coordinated action by various upper extremity muscles. The objective of this experimental study was to examine the effects of horizontal and vertical hand loads on upper extremity muscle activity during concentric pushing and pulling exertions. Twenty young female participants conducted repetitive pushing and pulling trials with three horizontal loads (1 kg, 2 kg, 3 kg) and two vertical loads (0.6 kg, 1.3 kg) in a seated posture, while the myoelectric activity of seven upper extremity and shoulder muscles were quantified. Study results indicate that the shoulder flexor and extensor muscles were more strongly associated with horizontal load, and elbow flexors were more sensitive to vertical load. The empirical data from this systematic evaluation can offer initial insights for ergonomic design and evaluation of hand tools or occupational tasks that involve repetitive pushing or pulling.

Ergonomics issues while using virtual reality (VR) headsets for text-intensive applications have not been studied. Measures of neck and shoulder discomfort and simulator sickness symptoms were quantified while participants were performing a document creation task for 60 min using a VR headset and a desktop monitor. During the task with the headset, participants rotated the head 2.7 times more frequently and used the neck extensor muscles 25.9% more, in average. They also rated the neck and shoulder discomfort 60% and 17.5% higher after the task. The simulator sickness symptoms were also rated significantly higher (p < .05) for the headset condition, with more pronounced differences in the symptoms related to visual discomfort. Results indicate that the physical discomforts due to the frequent head rotations and the headset weight, and visual discomforts due to difficulty in reading texts were the main issues of the VR headset for common office tasks. Practitioner summary: Ergonomics issues associated with the use of a VR headset for conducting office productivity work tasks have been evaluated in an experiment. Study results indicate that the development in the neck physical discomfort and visual discomfort may be the main barriers to the use of current VR headsets for office works. Abbreviations: VR: virtual reality; VDT: video display terminal; EMG: electromyography; MVC: maximum voluntary contraction; SSQ: simulator sickness questionnaire; ECG: electrocardiogram; NEMG: normalised electromyography.

Current organoid models are limited by their inability to mimic mature organ architecture and associated tissue microenvironments1,2. Here, we create multi-layered normal bladder assembloids and tumour assembloids by reconstituting tissue stem cell/tumour cell-derived organoids with multiple stromal components to represent an organized tissue architecture and functionality of adult bladder, and to mimic in vivo pathophysiological features of patient-derived urothelial carcinoma, respectively. Our assembloid model will facilitate development of an innovative model system for studying tissue regeneration and tumourigenesis at molecular and cellular levels, and also provide a unique experimental tool for establishing novel personalized therapeutic options, such as new drug screening strategies that are customized for different stages and types of cancer in individual patients.

Vaccination has greatly reduced the burden of human diseases caused by infectious pathogens. Systematic development of vaccine targets requires established protocols to assess immunogenicity and efficacy of such vaccine candidates. Using a leading schistosomiasis vaccine candidate, Sm-p80, as an example, we describe standardized approaches for testing the immunogenicity and efficacy of Schistosoma mansoni vaccine targets. Unlike other parasite systems in which sterile immunity is required, the goal of S. mansoni vaccine targets is overall reduction in morbidity. Methods related to the parasitological parameters described in this chapter allow for the testing of the prophylactic (reduction in adult worm burden), anti-pathology (liver and intestine egg retention), and transmission blocking (fecal egg expulsion and egg hatching rates) efficacies for the vaccine target. The RNA sequencing approaches provide basis for identification of molecular signatures predictive of desirable outcomes for schistosomiasis vaccines.

Quantification of intratumoral heterogeneity is essential for designing effective therapeutic strategies in the age of personalized medicine. In this study, we used a piezoelectric inkjet printer to enable analysis of intratumoral heterogeneity in a bladder cancer for the first time. Patient-derived tumor organoids were dissociated into single cell suspension and used as a bioink. The individual cells were precisely allocated into a microwell plate by drop-on-demand inkjet printing without any additive or treatment, followed by culturing into organoids for further analysis. The sizes and morphologies of the organoids were observed, so as the expression of proliferation and apoptotic markers. The tumor organoids also showed heterogeneous responses against chemotherapeutic agent. Further, we quantified mRNA expression levels of representative luminal and basal genes in both type of tumor organoids. These results verify the heterogeneous expression of various genes among individual organoids. This study demonstrates that the fully automated inkjet printing technique can be used as an effective tool to sort cells for evaluating intratumoral heterogeneity.

Vaccination has greatly reduced the burden of human diseases caused by infectious pathogens. Systematic development of vaccine targets requires established protocols to assess immunogenicity and efficacy of such vaccine candidates. Using a leading schistosomiasis vaccine candidate, Sm-p80, as an example, we describe standardized approaches for testing the immunogenicity and efficacy of Schistosoma mansoni vaccine targets. Unlike other parasite systems in which sterile immunity is required, the goal of S. mansoni vaccine targets is overall reduction in morbidity. Methods related to the parasitological parameters described in this chapter allow for the testing of the prophylactic (reduction in adult worm burden), anti-pathology (liver and intestine egg retention), and transmission blocking (fecal egg expulsion and egg hatching rates) efficacies for the vaccine target. The RNA sequencing approaches provide basis for identification of molecular signatures predictive of desirable outcomes for schistosomiasis vaccines.

Crowdsourced financial information platforms often allow content contributors to publish equity research anonymously. This study examines whether investors value or discount information in anonymous equity research. In the short window around research releases, we find that investors’ stock price reaction to anonymous research is muted in comparison to non-anonymous research. Consistent with credibility concerns influencing investor response, we document that this discount to anonymous research dissipates as the monitoring of content contributors intensifies and as authors develop a reputation for high-quality reporting. In addition, we perform a content analysis on the research reports and find that the muted market reaction to anonymous equity research is robust to controlling for textual attributes of information content, further supporting our inference that investors’ are concerned about the credibility of anonymous equity research.

Schistosomiasis is of public health importance to an estimated one billion people in 79 countries. A vaccine is urgently needed. Here, we report the results of four independent, double-blind studies of an Sm-p80-based vaccine in baboons. The vaccine exhibited potent prophylactic efficacy against transmission of Schistosoma mansoni infection and was associated with significantly less egg-induced pathology, compared with unvaccinated control animals. Specifically, the vaccine resulted in a 93.45% reduction of pathology-producing female worms and significantly resolved the major clinical manifestations of hepatic/intestinal schistosomiasis by reducing the tissue egg-load by 89.95%. A 35-fold decrease in fecal egg excretion in vaccinated animals, combined with an 81.51% reduction in hatching of eggs into the snail-infective stage (miracidia), demonstrates the parasite transmission-blocking potential of the vaccine. Substantially higher Sm-p80 expression in female worms and Sm-p80-specific antibodies in vaccinated baboons appear to play an important role in vaccine-mediated protection. Preliminary analyses of RNA sequencing revealed distinct molecular signatures of vaccine-induced effects in baboon immune effector cells. This study provides comprehensive evidence for the effectiveness of an Sm-p80-based vaccine for schistosomiasis.

A 40-year-old woman with chronic gastritis who did not have alcoholism had lost 50 pounds in the past 45 days and presented with dyscoordination and diplopia. Examination showed confabulation, ophthalmoplegia, nystagmus, and appendicular ataxia. Brain MRI (Figure) showed diffusion-weighted imaging and fluid-attenuated inversion recovery abnormalities suggestive of Wernicke encephalopathy (WE). With classic triad of WE and MRI findings, IV thiamine 500 mg TID was administered for 3 days, followed by maintenance oral thiamine. The patient showed substantial improvement. Thiamine replacement therapy should be considered in patients with malnutrition or malabsorption as it is important in maintaining cellular osmotic gradients. Thiamine deficiency may lead to cytotoxic edema, especially in high metabolic demand regions such as thalami and mammillary bodies.1

Ground-level traffic lights or safety signs have been introduced recently as a prevention measure for smartphone-related pedestrian accidents. However, quantitative evaluation of smartphone users' detection performance during distracted walking has been scarce. A laboratory experiment was conducted to evaluate the performance of detecting ground-level visual cues during the concurrent use of a smartphone while walking. Thirty-eight young smartphone users performed ground-level visual cue detection trials, 1) while walking upright on a treadmill without using a smartphone; 2) when conducting one-handed browsing while walking; and, 3) when conducting two-handed texting while walking. Visual cues were presented on the ground at 24 locations by a ceiling-mounted projector, and participants were asked to respond verbally when they perceived the appearance of each cue. Study results show that the concurrent use of a smartphone decreased the detection rate significantly (p < 0.05) from 93.5 % to 76.3∼74.1 %, and increased the reaction time from 0.90 s to 1.04∼1.15 s. Among the 24 cue locations, cues that were presented closer to participants were detected significantly (p < 0.05) more often and faster than cues that were shown at further locations. The results of this laboratory-based study imply that the ground-level signals might not be detected well by smartphone users, specifically when they were conducting more demanding tasks such as texting while walking. However, the laboratory conditions were confined to a specific usage environment; therefore, future research should be focused on the situation awareness of smartphone users under various usage scenarios and more realistic environments.

In bladder, loss of mammalian Sonic Hedgehog (Shh) accompanies progression to invasive urothelial carcinoma, but the molecular mechanisms underlying this cancer-initiating event are poorly defined. Here, we show that loss of Shh results from hypermethylation of the CpG shore of the Shh gene, and that inhibition of DNA methylation increases Shh expression to halt the initiation of murine urothelial carcinoma at the early stage of progression. In full-fledged tumors, pharmacologic augmentation of Hedgehog (Hh) pathway activity impedes tumor growth, and this cancer-restraining effect of Hh signaling is mediated by the stromal response to Shh signals, which stimulates subtype conversion of basal to luminal-like urothelial carcinoma. Our findings thus provide a basis to develop subtype-specific strategies for the management of human bladder cancer., eLife digest In order to grow, cancer cells shut down or over-activate genes that normally maintain a cell’s health. The Sonic Hedgehog gene – named after a Japanese cartoon character – is associated with the cancer of several tissues, including the bladder. In 2014, researchers found that losing the Sonic Hedgehog gene, Shh for short, is necessary for bladder cancers to become aggressive: Shh signals prompt healthy cells near the tumor to inhibit the cancer cell growth, whilst aggressive bladder cancer cells turn off the Shh gene. Kim et al. – including many of the researchers involved in the 2014 work – now investigate how cancer cells switch off the Shh gene and what effect it has on bladder cancer cells and their surrounding tissue when turned back on. DNA sequencing bladder cancer cells derived from human patients showed that there were no genetic deletions or mutations within the gene. However, the sequence and nearby regions of DNA did contain methylations – a chemical modification that generally switches genes off. When mice with early stages of bladder cancer were treated with a drug that inhibits methylation, the Shh gene turned back on, the bladder cancers stopped growing and the tumors stayed at an early stage of development. When the same drug was used on mice with aggressive bladder cancer, this caused non-cancer cells in the surrounding tissue to respond to Shh and send restraining signals back to the tumor. These signals eventually stopped cancer growth and converted the tumor into a less aggressive type of bladder cancer. Additionally, Kim et al. saw that blocking methylation had the same effect on human bladder cancer cells that had been transplanted into mice. These results therefore indicate that Shh could be a new target for cancer treatments. For instance, drugs that decrease methylation and turn on the gene could be a way of managing cancer in patients with aggressive bladder cancers, which often show low activity of the gene. However, future studies are needed to understand what exactly happens within cancer cells during tumor conversion and to determine if this kind of intervention could have unintended consequences.

Sm-p80-based vaccine efficacy for Schistosoma mansoni was evaluated in a baboon model of infection and disease. The study was designed to replicate a human vaccine implementation scenario for endemic regions in which vaccine would be administered following drug treatment of infected individuals. In our study, the Sm-p80-based vaccine reduced principal pathology producing hepatic egg burdens by 38.0% and egg load in small and large intestines by 72.2% and 49.4%, respectively, in baboons. Notably, hatching rates of eggs recovered from liver and small and large intestine of vaccinated animals were significantly reduced, by 60.4%, 48.6%, and 82.3%, respectively. Observed reduction in egg maturation/hatching rates was supported by immunofluorescence and confocal microscopy showing unique differences in Sm-p80 expression in worms of both sexes and matured eggs. Vaccinated baboons had a 64.5% reduction in urine schistosome circulating anodic antigen, a parameter that reflects worm numbers/health status in infected hosts. Preliminary analyses of RNA sequencing revealed unique genes and canonical pathways associated with establishment of chronic disease, praziquantel-mediated parasite killing, and Sm-p80-mediated protection in vaccinated baboons. Overall, our study demonstrated efficacy of the Sm-p80 vaccine and provides insight into some of the epistatic interactions associated with protection.

We explore the role of investor relations (IR) in debt markets. Using earnings announcements as a laboratory, we examine whether, when, and to what extent IR departments help credit investors assimilate information. We find that the presence of IR decreases (increases) the negative (positive) impact on CDS spreads stemming from bad (good) earnings news, suggesting that IR efforts improve information precision and reduce transparency risk. Cross-sectional analyses suggest that IR matters more when uncertainty is high and creditors are concerned about the credit-risk implications of firm performance. We also find that IR firms receive higher credit ratings and fewer covenants when issuing bonds, and CDS markets react less negatively when IR firms’ bond ratings are downgraded below investment grade. Because firms choose their IR activities, we show that our inferences are robust to multiple methods of addressing endogeneity. Overall, we find that IR departments are influential in debt markets.

Peroxisome proliferator-activated receptor γ coactivator 1α (PGC1α) is a key modulator of mitochondrial biogenesis. It is a coactivator of multiple transcription factors and regulates metabolic processes. However, little is known about the expression and function of PGC1α in glioblastoma multiforme (GBM), the most prevalent and invasive type of brain tumor. The purpose of the present study was to investigate the biological function, localization and expression of PGC1α in GBM. It was observed that PGC1α expression is increased in the tumor cells, and a higher level of expression was observed in the mitochondria. Bioinformatics analyses identified that metabolic and mitochondrial genes were highly expressed in GBM cells, with a high PGC1α mRNA expression. Notably, mitochondrial function-associated genes were highly expressed in cells alongside high PGC1α expression. Collectively, the results of the present study indicate that PGC1α is associated with mitochondrial dysfunction in GBM and may have a role in tumor pathogenesis and progression.

Long-term stress during pregnancy causes neurologic deficits to offspring with altered gamma-aminobutyric acid (GABA) system in the brain. However, it is not clear how prenatal stress affects the maturing GABAergic interneurons and the resulting abnormalities in infantile seizures. Here, we showed that prenatal stress alters the maturation of GABA inhibitory system using a seizure model induced by prenatal stress. Prenatal stress with betamethasone or acute immobilization stress (AIS) on gestational day 15 increased the seizure susceptibility to N-methyl-d-aspartate-triggered spasms on postnatal day 15. The expression of GABA was lower in the prenatally stressed group, which compromise the decrease of glutamate decarboxylase 67-immunopositive cells. Prenatal stress markedly decreased the expression of K(+)/Cl(-) co-transporter (KCC2) in the cortex. GABA induced membrane depolarization demonstrated prenatal stress models had significant higher membrane depolarization compared to control. GABA increased KCC2 expression in cultured cortex-containing slices. Taken together, our results showed that prenatal stress with betamethasone or AIS altered the maturation of GABAergic progenitors and resulted in the lack of GABA input, which in turn, decreased KCC2 expression and lowered seizure threshold. We conclude that delayed GABA excitatory/inhibitory shift would render the cortical neuronal circuit more susceptible to excitatory input in prenatal stress induced seizure.

This study explores the proximal context of knowledge sharing in networked communities, and identifies relationships among variables in shaping knowledge sharing behaviors. Taking an integrative pe...

Endoplasmic reticulum (ER) stress has been implicated in neurodegenerative diseases, but its role in neuropathic pain remains unclear. In this study, we examined the ER stress and the unfolded protein response (UPR) activation in a L5 spinal nerve ligation (SNL)-induced rat neuropathic pain model. SNL-induced neuropathic pain was assessed behaviorally using the CatWalk system and histologically with microglial activation in the dorsal spinal horn. L5 SNL induced BIP upregulation in the neuron of superficial laminae of dorsal spinal horn. It also increased the level of ATF6 and intracellular localization into the nuclei in the neurons. Moreover, spliced XBP1 was also markedly elevated in the ipsilateral spinal dorsal horn. The PERK-elF2 pathway was activated in astrocytes of the spinal dorsal horn in the SNL model. In addition, electron microscopy revealed the presence of swollen cisternae in the dorsal spinal cord after SNL. Additionally, inhibition of the ATF6 pathway by intrathecal treatment with ATF6 siRNA reduced pain behaviors and BIP expression in the dorsal horn. The results suggest that ER stress might be involved in the induction and maintenance of neuropathic pain. Furthermore, a disturbance in UPR signaling may render the spinal neurons vulnerable to peripheral nerve injury or neuropathic pain stimuli.

Despite recent improvements in standard pharmacologic treatments of multiple myeloma (MM), immunotherapy may prove to be more effective due to its higher specificity and lower toxicity. Indeed, current frontline MM therapies are based on the use of drugs such as thalidomide, lenalidomide, and bortezomib, which are associated to serious side effects and undermined by the development of multidrug resistance in recurring disease. The potential for immune surveillance against tumor recurrence has been clearly exemplified by the superior effectiveness of allogeneic hematopoietic stem cell transplantation, residing in alloreactive donor T cells, compared with autologous HSCT. However, allo-HSCT has major side effects. Many of the antigens driving graft-versus-tumor activity are shared by normal host tissues. Such a setting generates graft-versus-host disease, strongly limiting complete response rates and survival. Cancer testis antigens (CTAs) are a family of proteins with testis-restricted expression that are not present, or barely present, in other tissues, but are associated with many tumors. As the testes are immunologically privileged sites lacking HLA expression, CTA are suggested to be ideal targets for immunotherapy. Here we characterized the expression of two novel MM CTA, Ropporin and AKAP4, in tumor plasma cells from patients and cell lines. Additionally, we showed that Ropporin and AKAP4 are strongly immunogenic and are therefore potential targets for effective MM vaccines. Additionally, because of their preferential expression in tumor cells, Ropporin and AKAP4 are outstanding biomarkers for tumor detection and monitoring in vivo. Similarly to other malignancies, virtually any innovative treatment for MM requires a pre-clinical assessment, which largely relies on the use of animal models to evaluate the anti-tumor potential and possible toxicities. Recently, a modified NOD strain, carrying disrupted Rag1 and the IL2-R γ chain genes (NOD-Rag1null/IL2rgnull, NRG), has been reported to tolerate higher levels of radiation compared with NOD/SCID strain and to allow for efficient engraftment of human tumors and HSC. The development of successful animal models for MM also relies on the choice of the biomarkers used to track the disease course and to identify tumor cells. Here we used the NRG strain to establish an innovative model of MM, allowing for the growth and the spread of MM cell lines and primary patients’ cells, which can be monitored by using AKAP4 as a tumor biomarker. Citation Format: Maurizio Chiriva-Internati, Eunjee Kim, Alejandro Figueroa, Lauren Littlefield, Charles Saadeh, Raymond Wade, Vijay Giridhar, Jesse Mer, Leonardo Mirandola, Yuefei Yu, Fred Hardwicke, Nicholas D'Cunha, Lukman Tijani, Diane D. Nguyen, Jose A. Figueroa, Everardo Cobos. Cancer/testis antigens for immunotherapy and detection of multiple myeloma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3535. doi:10.1158/1538-7445.AM2013-3535

Many Korean students feel quite frustrated by native speakers’ fast talk, especially in a noisy situation. In this study, it was examined how well 33 Korean university students repeat 48 recorded English sentences at normal speed, fast speed, normal speed mixed with noise, and fast speed mixed with noise. The subject’s production was scored by the percent ratios of correctly produced words to the total words in each sentence. Results showed that overall the student group correctly repeated around 65% of all the words, while the native speakers demonstrated almost perfect performances. Students achieved 69% and 61% accuracy in their repetition of content and function words, respectively. The high‐proficiency group outperformed the low‐proficiency group, particularly in their repetition of function words. Student’s accuracy of repetition remarkably dropped when both the speed and noise of normal sentences were modified. The noise condition seemed to have the strongest effect on their accuracy. Finally, it was observed that the more words a stimulus sentence had, the harder the Korean students found it to repeat correctly. Those results may be helpful for English teachers to develop better teaching materials for listening skills and to offer some criteria of proficiency level in English.