A Rare Case of Achalasia Sigmoid Esophagus Obstructed by Food Bolus.
Achalasia is a primary esophageal motility disorder that involves a failure of the lower esophageal sphincter to relax in response to swallowing. Specifically, the lower esophageal sphincter becomes hypertensive, and there is an absence of peristalsis in the esophagus. The pathophysiology is thought to be due to a loss of inhibitory nerve function from an autoimmune attack that targets the esophageal myenteric nerves. As a result, these abnormalities lead to a functional obstruction at the gastroesophageal junction. In severe cases, achalasia may present as a "sigmoid esophagus," a term used to describe the dilation and distortion of the cervical esophagus. In this case report, we discuss a patient with a known history of achalasia who presented with extra-esophageal symptoms including respiratory distress and tracheal compression from an esophagus dilated with a food impaction. She was found to have a sigmoid esophagus and required direct endoscopy and removal of the food bolus. We will review the pathogenesis of achalasia as well as medical and surgical approaches to treating severe achalasia as presented through other case reports.


Tissue plasminogen activator therapy of rabbit nephrotoxic nephritis.
To study the efficacy of tissue plasminogen activator (PA) therapy to prevent deteriorating renal function in experimental proliferative glomerulonephritis we used a model of nephrotoxic nephritis induced in rabbits by injection of antiglomerular basement membrane antiserum. Saline or recombinant tissue plasminogen activator (rt-PA, 1.3 mg/kg body weight) was infused daily for 7 days starting from day 7 after the injection of antiglomerular basement membrane antiserum when the disease had been already triggered. Animals were killed on day 14. Rabbits given saline had abundant deposits of fibrin and crescents in about 67% of glomeruli. rt-PA significantly protected animals from glomerular fibrin deposition and crescent formation with respect to saline-treated animals. Renal function measured as creatinine clearance was dramatically impaired in rabbits given saline. Treatment with rt-PA ameliorated the renal function impairment of nephrotoxic nephritis. rt-PA did not produce a systemic fibrinolytic state as indicated by alpha 2-antiplasmin level measurement. These results suggest that tissue PA may have important implications in preventing renal function deterioration in humans with crescentic glomerulonephritis and fibrin depositions.


Early molecular response of marrow disease to biologic therapy is highly prognostic in neuroblastoma.
A promising treatment strategy for stage 4 neuroblastoma patients is the repeated application of anti-GD2 immunotherapy after activating myeloid effectors with granulocyte-macrophage colony-stimulating factor (GM-CSF). To use early marrow response as a prognostic marker is particularly relevant for patients not likely to benefit from this therapy. Eighty-six stage 4 neuroblastoma patients older than 1 year at diagnosis were classified in four clinical groups on protocol entry: complete remission or very good partial remission (n = 33), primary refractory (n = 33), secondary refractory (n = 10), and progressive disease (n = 10). Bone marrow samples collected before and following treatment were assayed for GD2 synthase mRNA by real-time reverse transcriptase polymerase chain reaction. Response and survival analyses were performed on posttreatment samples before the third cycle at 1.8 months from protocol entry. GD2 synthase mRNA was evident in pretreatment marrow samples of the four clinical groups (42%, 52%, 60%, and 80% of samples, respectively), with median transcript level of 10.0, 16.6, 26.5, and 87.2, respectively. This marker became negative following antibody plus GM-CSF in 77% of complete remission or very good partial remission, 45% of primary refractory, 25% of secondary refractory, and 0% of progressive disease group. Progression-free survival was statistically different between responder and nonresponder groups (P <.0001). Among patients with minimal residual disease, molecular responders had a significantly lower risk of disease progression at a median follow-up of 29.8 months (P =.0001). GD2 synthase mRNA is a sensitive response marker of neuroblastoma in the bone marrow. It is particularly useful for minimal residual disease evaluation and may potentially be useful as an early predictor of resistance to antibody plus GM-CSF immunotherapy.


Locking stand-alone cages versus anterior plate constructs in single-level fusion for degenerative cervical disease: a systematic review and meta-analysis.
To conduct a meta-analysis to compare the clinical and radiological outcomes in single-level anterior cervical discectomy and fusion (ACDF) surgery for degenerative cervical disease performed by either single-level locking stand-alone cage (LSC) or anterior plate construct (APC). We performed a comprehensive database search of Medline, PubMed, EMBASE and Cochrane Database of Systematic Reviews according to PRISMA guidelines and identified six articles that satisfied our inclusion criteria. We excluded all non-English language articles and articles which did not directly compare LSC and APC. Only papers which focussed on single-level ACDF were included in the study. There were no significant differences in blood loss, clinical outcomes (JOA, VAS, NDI scores) or radiological outcomes (cervical lordosis, segmental Cobb angle, subsidence and fusion) between the two groups. Operative time was significantly shorter in the LSC group (MD 7.2 min, 95% CI 0.3-14.1, p = 0.04). APC was associated with a statistically significant increase in dysphagia in the follow-up period (OR 6.2, 95% CI 1.0-36.6, p = 0.05). LSC and APC have similar clinical and radiological outcomes. Further blinded randomised trials are required to establish conclusive evidence in favour of LSC with regards to minimising post-operative dysphagia. We also encourage future studies to make use of formalised dysphagia outcome measures in reporting complications.


Neo-antigen specific T cell responses indicate the presence of metastases before imaging.
Non-small cell lung cancer (NSCLC) causes 19% of all Australian cancer deaths, with a 5-year survival post-resection of around 60%. Post-operative recurrence is due to metastases that were undetectable pre-operatively, or growth of microscopic locoregional residual disease. However, post-operative imaging modalities typically only detect more advanced tumours; where PET-CT has a detection limit of 6-7 mm. Detection of small deposits of lung metastatic disease is of importance in order to facilitate early and potentially more effective treatment. In this study, in a murine model of lung metastatic disease, we explore whether neo-antigen specific T cells are a sensitive marker for the detection of lung cancer after primary tumour resection. We determine lung metastatic disease by histology, and then compare detection by PET-CT and neo-antigen specific T cell frequency. Detection of lung metastatic disease within the histology positive group by PET-CT and neo-antigen specific T cell frequency were 22.9% and 92.2%, respectively. Notably, neo-antigen specific T cells in the lung draining lymph node were indicative of metastatic disease (82.8 ± 12.9 spots/105 cells; mean ± SE), compared to healthy lung control (28.5 ± 8.6 spots/105 cells; mean ± SE). Potentially, monitoring tumour neo-antigen specific T cell profiles is a highly sensitive method for determining disease recurrence.


Lobular carcinoma of the breast with hybrid myoepithelial and secretory ("myosecretory") cell differentiation.
Three cases of lobular carcinoma of the breast showing a complex morphology that included myoepithelial cell differentiation are reported. One case was a pure in situ acinar lesion, while the other 2 cases were in situ and invasive carcinomas. Three different cell types were seen in these tumors: one was the phenotype commonly seen in the garden variety of in situ lobular carcinoma (LCIS) constituted by noncohesive round to ovoid cells with round nuclei and positivity for epithelial membrane antigen (EMA), estrogen receptor (ER), and progesteron receptor (PR). E-cadherin was negative in these cells. The second type was represented by cohesive elements with irregular nuclei. These cells were immunoreactive for smooth muscle actin, calponin, keratin 14, p63, and e-cadherin. EMA, ER, and PR were consistently negative. The third type, seen in a minority of cell population of case nos. 2 and 3, consisted of cells showing at the same time EMA and smooth muscle actin in their cytoplasm. This type was defined as "hybrid myosecretory cell" to highlight contractile and secretory properties present at the same time. Cells with hybrid features probably indicate that myoepithelial and secretory cells are strictly related and the existence of a stem cell, at least for these cases, is not necessary.


Disassociation of the release of histamine and arachidonic acid metabolites from osmotically activated basophils and human lung mast cells.
Upon activation by most stimuli, basophils and human lung mast cells simultaneously release histamine and arachidonic acid metabolites. Hyperosmolar activation was examined, and both cell types were shown to release histamine but little or no leukotriene C4 or D4 (LTC4/D4) and, in the case of mast cells, little or no prostaglandin D2 (PGD2). In addition, hyperosmolar buffers were capable of preventing the formation of LTC4/LTD4 in basophils stimulated by anti-IgE when added simultaneously, or 2, 5, or 10 min after, the addition of anti-IgE. Catabolism of PGD2 and LTC4/D4 was not increased. Experiments with cell lysates demonstrated that intracellular formation, rather than secretion, was arrested in hyperosmolar buffers. We conclude that this selective inhibition of mediator production is a unique response of mast cells and basophils to osmotic activation. Although the mechanism of this selective cellular response is not clear, these in vitro observations have important therapeutic and pathophysiologic implications for the airway response to hyperosmolar stimuli.


Cost-effectiveness analysis of strategies for HER2 testing of breast cancer patients in France.
A cost-effectiveness analysis was conducted comparing diagnostic strategies for determining the HER2 status of invasive breast carcinomas, as an indication for trastuzumab at metastatic relapse. A decision tree compared five strategies distinguished by (i) the use of immunohistochemical (IHC) and/or fluorescent in situ hybridization (FISH) techniques, and (ii) the test schedule (at initial diagnosis or metastatic relapse). Most cost and effectiveness data came from a French multicentric study of 2,045 patients from eight hospitals. We were not able to select final criteria for trastuzumab effectiveness, because published data rely on IHC techniques not used in France (i.e., HercepTest). We, therefore, selected two intermediate criteria for inappropriate treatment at relapse, that is, patients with HER2-amplified tumors not receiving trastuzumab (Criterion 1) and HER2-nonamplified tumors improperly treated with trastuzumab (Criterion 2). Sensitivity analyses were then performed to assess the robustness of the results to (i) discount rate, (ii) cost of FISH, and (iii) tissue fixation technique. The strategy using IHC at diagnosis was dominated by the four other strategies. Among these approaches, the only efficient strategy for both criteria was IHC used alone at metastatic relapse; strategies using FISH, or IHC followed by FISH on IHC2+ cases were efficient for Criterion 1, whereas IHC followed by FISH on IHC2+ and 3+ cases was efficient for Criterion 2. Determining HER2 status at diagnosis, as an indication for trastuzumab at metastatic relapse, incurs substantial incremental costs, which do not appear to be justified. No other strategy can be excluded at first.


[Bases of central venous catheterization].
Central venous catheterization is a frequently performed procedure in internal medicine units. Residents in training frequently share the same questions, doubts and fears about this procedure : "Should I perform a subclavian catheterization in a patient with mild thrombopenia?"; "Which site has the lesser complication rate?"; "After how long does a catheter need to be replaced?". This mini-review of the current literature tries to answer this and other questions.


Symplekin and multiple other polyadenylation factors participate in 3'-end maturation of histone mRNAs.
Most metazoan messenger RNAs encoding histones are cleaved, but not polyadenylated at their 3' ends. Processing in mammalian cell extracts requires the U7 small nuclear ribonucleoprotein (U7 snRNP) and an unidentified heat-labile factor (HLF). We describe the identification of a heat-sensitive protein complex whose integrity is required for histone pre-mRNA cleavage. It includes all five subunits of the cleavage and polyadenylation specificity factor (CPSF), two subunits of the cleavage stimulation factor (CstF), and symplekin. Reconstitution experiments reveal that symplekin, previously shown to be necessary for cytoplasmic poly(A) tail elongation and translational activation of mRNAs during Xenopus oocyte maturation, is the essential heat-labile component. Thus, a common molecular machinery contributes to the nuclear maturation of mRNAs both lacking and possessing poly(A), as well as to cytoplasmic poly(A) tail elongation.


Anti-vascular endothelial growth factor therapy in breast cancer.
Neo-angiogenesis is a critical process for tumor growth and invasion and has become a promising target in cancer therapy. This manuscript reviews three currently relevant anti-angiogenic agents targeting the vascular endothelial growth factor system: bevacizumab, ramucirumab and sorafenib. The efficacy of anti-angiogenic drugs in adjuvant therapy or as neo-adjuvant treatment has been estimated in clinical trials of advanced breast cancer. To date, the overall observed clinical improvements are unconvincing, and further research is required to demonstrate the efficacy of anti-angiogenic drugs in breast cancer treatments. The outcomes of anti-angiogenic therapy have been highly variable in terms of tumor response. New methods are needed to identify patients who will benefit from this regimen. The development of biomarkers and molecular profiling are relevant research areas that may strengthen the ability to focus anti-angiogenic therapy towards suitable patients, thereby increase the cost-effectiveness, currently estimated to be inadequate.


Evaluation of Alveolar Bone Microstructure around Impacted Maxillary Canines Using Fractal Analysis in Dravidian Population: A Retrospective CBCT Study.
The aim of this study was to assess alveolar bone microstructure around impacted maxillary canines derived from fractal analysis. The present study was a retrospective cone-beam computed tomography (CBCT) study. In total, 61 scans (25 males, 36 females; age range - 12-28 years) were analyzed. About 64 × 64-pixel regions of interest (ROI) in the maxillary alveolar process containing trabecular bone between the premolars were selected. ImageJ software was utilized to process images and bone density was assessed by determining bone surface area (BSA) and bone marrow surface area (BMSA) for the impacted and nonimpacted sides separately. Selected fractals were plotted in a histogram using box-counting method and the results were tabulated. Paired t-tests were used to determine significant differences between the groups and gender differences. For both buccally and palatally impacted maxillary canines, BSA was increased, BMSA decreased in the region of the impacted canine and the difference was statistically significant (p <0.05) in both genders. Bone fractal dimension (FD) values were greater in the region of the impacted canine for both buccally (1.47 > 1.21) and palatally (1.53 > 1.43) displaced canines, while bone marrow FD values were greater in the region of the nonimpacted canine for both buccally (1.37 > 1.28) and palatally displaced canines (1.41 > 1.33). Females had significantly higher BMSA than males around impacted canines (p <0.05). Denser bone microstructure was noted around impacted canines when compared with fully erupted canines. No gender-related differences were noted for BSA, whereas BMSA was higher in females implying lower bone density when compared with males. Retrospective evaluation of bone microstructure surrounding unerupted/impacted canines can provide analytical information about treatment prognosis and anchorage considerations. With FD analysis of CBCT images, BSA and BMSA can be measured and bone density estimated in a reliable manner.


HIV-1 Drug Resistance in ART-Naïve Individuals in Myanmar.
Estimating the prevalence and characterizing the transmission of HIV-1 drug resistance in treatment-naïve individuals are very important in the prevention and control of HIV/AIDS. As one of the areas most affected by HIV/AIDS, few data are currently available for HIV-1 drug resistance in antiretroviral therapy (ART)-naïve individuals in Myanmar, which borders Yunnan, China. HIV-1 pol sequences from ART-naïve HIV-1-infected individuals during 2008 and 2014 in Myanmar were retrieved from our previous studies. HIV-1 transmitted drug resistance (TDR) and susceptibility to antiretroviral drugs were predicted using the Stanford HIVdb program. HIV-1 transmission cluster (TC) was determined by Cluster Picker. A total of 169 partial pol sequences from ART-naïve HIV-1 positive Burmese were analyzed. The prevalence of TDR was 20.1%. CRF01_AE and BC recombinants appeared to have a higher prevalence of TDR than other subtypes. The V179D/T was found to be very common in the China-Myanmar border region and was involved in half of the transmission clusters formed by HIV-1 drug-resistance strains in this region. Comparison showed that drug-resistance mutation profile in Myanmar was very similar to that in Dehong prefecture of Yunnan. By further phylogenetic analysis with all available sequences from the China-Myanmar border region, four HIV-1 drug-resistance-related TCs were identified. Three of them were formed by Burmese long-distance truck drivers and the Burmese staying in Yunnan, and another was formed by Burmese injection drug users staying in Myanmar and Yunnan. These results suggest a potential transmission link of HIV-1 drug resistance between Myanmar and Yunnan. Given the high prevalence of TDR in Myanmar, and the potential risk of cross-border transmission of HIV-1 drug-resistant strains between Myanmar and Yunnan, China, ongoing monitoring of HIV-1 drug resistance in ART-naïve individuals will provide a guideline for clinical antiretroviral treatment and benefit the prevention and control of HIV/AIDS in this border region.


Factors affecting uptake of cervical cancer screening among clinic attendees in Trelawny, Jamaica.
Use of the Pap test has resulted in a decline in cervical cancer mortality in developed countries. Yet, despite established cervical cancer screening programs, a significant portion of Jamaican women are not undergoing screening for cervical cancer. This study was carried out to identify factors that affect Jamaican women's decisions to screen for cervical cancer. A population survey was administered to 367 clinic-attending women 25 to 54 years of age in the Parish of Trelawny from May to July of 2005. An interviewer-administered questionnaire assessed the women's knowledge, attitudes, and practices regarding cervical cancer and cervical cancer screening. Overall, 11% of the women had never had a Pap smear and only 38% had a Pap test within the last year. Annual visits to a health provider have a strong influence on women's decisions to regularly screen for cervical cancer. Provider recommendation also positively affected initial receipt of a Pap smear as well as continued regular screening. Programs that promote annual health checkups, encourage consistent provider recommendations, and emphasize screening as a preventive measure might positively influence women's decisions to screen for cervical cancer.


Phenotype-based cell-specific metabolic modeling reveals metabolic liabilities of cancer.
Utilizing molecular data to derive functional physiological models tailored for specific cancer cells can facilitate the use of individually tailored therapies. To this end we present an approach termed PRIME for generating cell-specific genome-scale metabolic models (GSMMs) based on molecular and phenotypic data. We build >280 models of normal and cancer cell-lines that successfully predict metabolic phenotypes in an individual manner. We utilize this set of cell-specific models to predict drug targets that selectively inhibit cancerous but not normal cell proliferation. The top predicted target, MLYCD, is experimentally validated and the metabolic effects of MLYCD depletion investigated. Furthermore, we tested cell-specific predicted responses to the inhibition of metabolic enzymes, and successfully inferred the prognosis of cancer patients based on their PRIME-derived individual GSMMs. These results lay a computational basis and a counterpart experimental proof of concept for future personalized metabolic modeling applications, enhancing the search for novel selective anticancer therapies.


Variability in behavior and production among dairy cows fed under differing levels of competition.
The objective of this study was to investigate the effects of differing levels of competition for feed access on group-housed dairy cows, and on variations in behavior and productivity between individuals within each group. Eighteen lactating Holstein cows, averaging 77 ± 20 d in milk with a production of 46 ± 7 kg/d at the start of the trial, were divided into subgroups of 3 and fed a total mixed ration 3×/d. Groups were exposed to each of 3 competition levels: high (3 cows:1 feed bin), moderate (3 cows:2 feed bins), and low (3 cows:3 feed bins). Treatments were assigned in random order according to a modified Latin-square design, and each was applied for 10 d. Using an automated feed intake system, feeding behavior data (dry matter intake, feeding time, feeding rate, and meal patterns) were recorded for each cow on d 6 to 10 of each treatment period. Additional behavioral [sorting, rumination, competitive interactions (replacements), lying time] and production (milk yield and components) data were collected. Greater competition resulted in a reduction in feeding time (low = 202.6, moderate = 194.9, high = 183.6 min/d; SE = 8.84), and an increased rate of feed intake (low = 0.16, moderate = 0.18, high = 0.20 kg of dry matter/min; SE = 0.01), especially following fresh feed delivery and milking. Dry matter intake was similar across treatments (average of 29.1 kg/d). Meal length increased under high competition (low = 37.0, moderate = 36.6, high = 47.3 min/meal; SE = 5.05) due to greater non-feeding time within meals, which was approximately twice as long under high competition (low = 10.0, moderate = 10.8, high = 20.3 min/meal; SE = 3.24). Daily lying time (low = 10.2, moderate = 10.2, high = 9.5 h/d; SE = 0.51) and milk protein yield (low = 1.41, mod = 1.42, high = 1.36 kg/d; SE = 0.05) were reduced under high competition. Analysis of individual within-group variability, calculated as the daily standard deviation of each group, averaged across 5 recording days, revealed greater variability in feeding time, feeding rate, meal length, non-feeding time within meals, milk yield, milk fat composition (%), and milk fat component yield (kg/d) under high competition. These results suggest that at elevated competition levels, cows modify their feeding behavior to consume feed in a shorter period and devote a large portion of their mealtime toward waiting to gain feed access, resulting in reduced daily lying time. Furthermore, meal patterns and milk production vary greatly within groups of cows at high levels of competition for feed access.


Physical, chemical and kinetic factors affecting prion infectivity.
The mouse-adapted scrapie prion strain RML is one of the most widely used in prion research. The introduction of a cell culture-based assay of RML prions, the scrapie cell assay (SCA) allows more rapid and precise prion titration. A semi-automated version of this assay (ASCA) was applied to explore a range of conditions that might influence the infectivity and properties of RML prions. These include resistance to freeze-thaw procedures; stability to endogenous proteases in brain homogenate despite prolonged exposure to varying temperatures; distribution of infective material between pellet and supernatant after centrifugation, the effect of reducing agents and the influence of detergent additives on the efficiency of infection. Apparent infectivity is increased significantly by interaction with cationic detergents. Importantly, we have also elucidated the relationship between the duration of exposure of cells to RML prions and the transmission of infection. We established that the infection process following contact of cells with RML prions is rapid and followed an exponential time course, implying a single rate-limiting process.


Breastfeeding knowledge, attitudes, prior exposure, and intent among undergraduate students.
Understanding breastfeeding knowledge, attitudes, and exposures among nonpregnant youth who are likely to be future parents may provide significant pathways to successfully increasing breastfeeding as the normal, accepted way of feeding infants. However, based on a recent review of the literature, only 3 studies have assessed these factors in nonpregnant, young adults in the United States in the past 10 years. The objective of this study was to gather more recent data regarding breastfeeding knowledge, attitudes, and prior exposure among undergraduate university students. This was a cross-sectional survey, conducted in November 2010. A convenience sample, consisting of undergraduates in attendance in 2 sections of an introductory nutrition class at a large research university, was used for this project (N = 248). Breastfeeding knowledge was relatively good. However, overall breastfeeding attitudes were more neutral, which appeared to be explained by the belief that breastfeeding is painful, restrictive, and inconvenient, both in general and specifically for the working mother. Though support for breastfeeding in public was low, men were significantly less likely than women to believe it to be embarrassing or unacceptable. In addition, breastfeeding attitudes were more positive among older students and those who were breastfed as infants. Those who were breastfed as infants were also significantly more likely to intend to breastfeed future children. Though this sample indicates good breastfeeding knowledge, attitudes were more neutral, and support for breastfeeding in public appears low. This finding is contradictory and warrants further exploration.


How important are the influencing factors to the decision on whether to provide seafood in infant and young child feeding?
Seafood is recommended as part of a healthy, balanced introductory diet however, consumption rates are low in young children. Research has previously investigated the influences to seafood consumption in consumers and non-consumers however the importance of these factors in mothers' decisions on whether to provide seafood for their child during the early years is unknown. This study aimed to measure the importance of factors that influence mothers' decisions on providing seafood for their child during infant and young child feeding (six months to four years). A mixed method Q methodology and cognitive interview approach was used with 32 mothers in Scotland. Despite a large consensus of opinion between mothers (n = 20) on the importance of factors on their decision-making, two viewpoints emerged highlighting an importance placed on food attributes and the infant, and convenience and family-centred. This study is the first to quantify the influences on the decision to provide seafood during early years' feeding and could be used to inform and tailor seafood-based dietary promotions and interventions for parents.


Temporal dynamics of fMRI signal changes during conditioned interoceptive pain-related fear and safety acquisition and extinction.
Associative learning and memory mechanisms drive interoceptive signaling along the gut-brain axis, thus shaping affective-emotional reactions and behavior. Specifically, learning to predict potentially harmful, visceral pain is assumed to succeed within very few trials. However, the temporal dynamics of cerebellar and cerebral fMRI signal changes underlying early acquisition and extinction of learned fear signals and the concomitant evolvement of safety learning remain incompletely understood. 3 T fMRI data of healthy individuals from three studies were uniformly processed across the whole brain and the cerebellum. All studies employed differential delay conditioning (N = 94) with one visual cue (CS+) being repeatedly paired with visceral pain as unconditioned stimulus (US) while a second cue remained unpaired (CS-). During subsequent extinction (N = 51), all CS were presented without US. Behavioral results revealed increased CS+-aversiveness and CS--pleasantness after conditioning and diminished valence ratings for both CS following extinction. During early acquisition, the CS- induced linearly increasing neural activation in the insula, midcingulate cortex, hippocampus, precuneus as well as cerebral and cerebellar somatomotor regions. The comparison between acquisition and extinction phases yielded a CS--induced linear increase in the posterior cingulate cortex and precuneus during early acquisition, while there was no evidence for linear fMRI signal changes for the CS+ during acquisition and for both CS during extinction. Based on theoretical accounts of discrimination and temporal difference learning, these results suggest a gradual evolvement of learned safety cues that engage emotional arousal, memory, and cortical modulatory networks. As safety signals are presumably more difficult to learn and to discriminate from learned threat cues, the underlying temporal dynamics may reflect enhanced salience and prediction processing as well as increasing demands for attentional resources and the integration of multisensory information. Maladaptive responses to learned safety signals are a clinically relevant phenotype in multiple conditions, including chronic visceral pain, and can be exceptionally resistant to modification or extinction. Through sustained hypervigilance, safety seeking constitutes one key component in pain and stress-related avoidance behavior, calling for future studies targeting the mechanisms of safety learning and extinction to advance current cognitive-behavioral treatment approaches.


Antitumour effect of abrin on transplanted tumours in mice.
Abrin, a galactose specific lectin was purified using sepharose 4B affinity column from seeds of Abrus precatorius. It exhibited antitumour activity in mice when used at a sublethal dose of 7.5 micrograms/kg every alternate day for 10 days. Both intralesional and intraperiloneal (i.p.) administration of abrin was effective in reducing solid tumour mass development induced by Dalton's Lymphoma Ascites (DLA) and Ehrlich's Ascites Carcinoma (EAC) cells. DLA cell line was more sensitive to abrin than EAC. Abrin when injected i.p. increased the life span of ascites tumour bearing mice. Abrin when used simultaneously with tumour cells brought about maximum antitumour effect. On developed tumour masses, abrin administration brought about significant reduction in tumour volume, especially in DLA induced tumours. Prophylactic administration of abrin was found ineffective.


Optogenetic monitoring identifies phosphatidylthreonine-regulated calcium homeostasis in Toxoplasma gondii.
Toxoplasma gondii is an obligate intracellular parasite, which inflicts acute as well as chronic infections in a wide range of warm-blooded vertebrates. Our recent work has demonstrated the natural occurrence and autonomous synthesis of an exclusive lipid phosphatidylthreonine in T. gondii. Targeted gene disruption of phosphatidylthreonine synthase impairs the parasite virulence due to unforeseen attenuation of the consecutive events of motility, egress and invasion. However, the underlying basis of such an intriguing phenotype in the parasite mutant remains unknown. Using an optogenetic sensor (gene-encoded calcium indicator, GCaMP6s), we show that loss of phosphatidylthreonine depletes calcium stores in intracellular tachyzoites, which leads to dysregulation of calcium release into the cytosol during the egress phase of the mutant. Consistently, the parasite motility and egress phenotypes in the mutant can be entirely restored by ionophore-induced mobilization of calcium. Collectively, our results suggest a novel regulatory function of phosphatidylthreonine in calcium signaling of a prevalent parasitic protist. Moreover, our application of an optogenetic sensor to monitor subcellular calcium in a model intracellular pathogen exemplifies its wider utility to other entwined systems.


The host range of the male-killing symbiont Arsenophonus nasoniae in filth fly parasitioids.
The Son-killer bacterium, Arsenophonus nasoniae, infects Nasonia vitripennis (Hymenoptera: Pteromalidae), a parasitic wasp that attacks filth flies. This gammaproteobacterium kills a substantial amount of male embryos produced by an infected female. Aside from male death, the bacterium does not measurably affect the host, and how it is maintained in the host population is unknown. Interestingly, this bacterial symbiont can be transmitted both vertically (from mother to offspring) and horizontally (to unrelated Nasonia wasps developing in the same fly host). This latter mode may allow the bacterium to spread throughout the ecological community of filth flies and their parasitoids, and to colonize novel species, as well as permit its long-term persistence. We tested 11 species of filth flies and 25 species of their associated parasitoids (representing 28 populations from 16 countries) using diagnostic PCR to assess the bacterium's actual host range. In addition to 16S rRNA, two loci were targeted: the housekeeping gene infB, and a sequence with high homology to a DNA polymerase gene from a lysogenic phage previously identified from other insect symbionts. We identified infections of A. nasoniae in four species of parasitoids, representing three taxonomic families. Highly similar phage sequences were also identified in three of the four species. These results identify the symbiont as a generalist, rather than a specialist restricted solely to species of Nasonia, and also that horizontal transmission may play an important role in its maintenance.


Mental Health Nursing Education: An Instructor's View.
If you knew no one with a mental illness, what would mold your perceptions of someone with a mental illness? A movie character, a television actor, a description from a friend? Each of these explanations has been given to me by nursing students beginning their mental health nursing clinical rotation. Reconsideration of the limited amount of mental health education in nursing school is urgent. As we become more engrossed as a society in television and movies, the result appears to be a deceptive idea of what true mental illness entails. This piece shares personal insight from a mental health nursing educator and the transformation she witnesses in her students after a mental health clinical rotation.


Transanal Minimally Invasive Surgery for Local Excision of Benign and Malignant Rectal Neoplasia: Outcomes From 200 Consecutive Cases With Midterm Follow Up.
This study describes the outcomes for 200 consecutive transanal minimally invasive surgery (TAMIS) local excision (LE) for rectal neoplasia. TAMIS is an advanced transanal platform that can result in high quality LE of rectal neoplasia. Consecutive patients from July 1, 2009 to December 31, 2015 from a prospective institutional registry were analyzed. Indication for TAMIS LE was endoscopically unresectable benign lesions or histologically favorable early rectal cancers. The primary endpoints were resection quality, neoplasia recurrence, and oncologic outcomes. Kaplan-Meier survival analyses were used to describe disease-free survival (DFS) for patients with rectal adenocarcinoma that did not receive immediate salvage radical surgery. There were 200 elective TAMIS LE procedures performed in 196 patients for 90 benign and 110 malignant lesions. Overall, a 7% margin positivity and 5% fragmentation rate was observed. The mean operative time for TAMIS was 69.5 minutes (SD 37.9). Postoperative morbidity was recorded in 11% of patients, with hemorrhage (9%), urinary retention (4%), and scrotal or subcutaneous emphysema (3%) being the most common. The mean follow up was 14.4 months (SD 17.4). Local recurrence occurred in 6%, and distant organ metastasis was noted in 2%. Mean time to local recurrence for malignancy was 16.9 months (SD 13.2). Cumulative DFS for patients with rectal adenocarcinoma was 96%, 93%, and 84% at 1-, 2-, and 3-years. For carefully selected patients, TAMIS for local excision of rectal neoplasia is a valid option with low morbidity that maintains the advantages of organ preservation.


Asunaprevir (BMS-650032) for the treatment of hepatitis C virus.
Asunaprevir, a second-generation NS3 protease inhibitor of hepatitis C virus (HCV), exhibits strong antiviral activity against HCV genotypes 1 and 4, but relatively weak activity against genotypes 2 and 3. For chronic HCV infection, asunaprevir with daclatasvir as an interferon-free dual treatment achieves a sustained virologic response of nearly 90% in genotype 1b, and a triple regimen with beclabuvir achieves an sustained virologic response >90%. Asunaprevir and daclatasvir dual treatment can be safely and effectively administered to liver transplant recipients with recurrent HCV. The major drawback of asunaprevir is its low threshold to resistance, which can be overcome by combining it with other direct-acting antivirals. Further studies of asunaprevir in combination with other direct-acting antivirals for the treatment of patients with HCV genotypes 1 or 4 and renal impairment or end-stage renal disease under hemodialysis, HIV-coinfection and liver and/or kidney transplant recipients are warranted.


Boundary-Eliminated Pseudoinverse Linear Discriminant for Imbalanced Problems.
Existing learning models for classification of imbalanced data sets can be grouped as either boundary-based or nonboundary-based depending on whether a decision hyperplane is used in the learning process. The focus of this paper is a new approach that leverages the advantage of both approaches. Specifically, our new model partitions the input space into three parts by creating two additional boundaries in the training process, and then makes the final decision based on a heuristic measurement between the test sample and a subset of selected training samples. Since the original hyperplane used by the underlying original classifier will be eliminated, the proposed model is named the boundary-eliminated (BE) model. Additionally, the pseudoinverse linear discriminant (PILD) is adopted for the BE model so as to obtain a novel classifier abbreviated as BEPILD. Experiments validate both the effectiveness and the efficiency of BEPILD, compared with 13 state-of-the-art classification methods, based on 31 imbalanced and 7 standard data sets.


Effect of co-ingestion of amino acids with rice on glycaemic and insulinaemic response.
Consumption of high glycaemic index (GI) and glycaemic response (GR) food such as white rice has been implicated in the development of type 2 diabetes. Previous studies have reported the ability of individual amino acids to reduce GR of carbohydrate-rich foods. Because of the bitter flavour of amino acids, they have rarely been used to reduce GR. We now report the use of a palatable, preformed amino acid mixture in the form of essence of chicken. In all, sixteen healthy male Chinese were served 68 or 136 ml amino acid mixture together with rice, or 15 or 30 min before consumption of white rice. Postprandial blood glucose and plasma insulin concentrations were measured at fasting and every 15 min after consumption of the meal until 60 min after the consumption of the white rice. Subsequent blood samples were taken at 30-min intervals until 210 min. The co-ingestion of 68 ml of amino acid mixture with white rice produced the best results in reducing the peak blood glucose and GR of white rice without increasing the insulinaemic response. It is postulated that amino acid mixtures prime β-cell insulin secretion and peripheral tissue uptake of glucose. The use of ready-to-drink amino acid mixtures may be a useful strategy for lowering the high-GI rice diets consumed in Asia.


Gender Equality in Plastic Surgery Training: A Canadian Nationwide Cross-sectional Analysis.
Introduction: One of the important factors in achieving gender equity is ensuring equitable surgical training for all. Previous studies have shown that females get significantly lower surgical exposure than males in certain surgical specialties. Gender gap in surgical exposure has never been assessed in plastic surgery. To that end, the goal of this study was to assess if there are any differences in plastic surgery training between male and female residents. Methods: A survey was sent to all plastic surgery residency programs in Canada to assess the No. of surgeries residents operated on as a co-surgeon or primary assistant during their training. The survey also assessed career goals, level of interest in the specialty, and subjective perception of gender bias. Results: A total of 89 plastic surgery residents (59.3% participation rate) completed the survey and were included in the study. The average No. of reconstructive cases residents operated on as a co-surgeon or primary assistant was 245 ± 312 cases. There was no difference in either reconstructive or aesthetic surgery case logs between male and female residents (p > .05). However, a significantly larger proportion of females (39%) compared to males (4%) felt that their gender limited their exposure to surgical cases and led to a worsening of their overall surgical training (p < .001). Finally, a larger proportion of male residents were interested in academic careers while a larger proportion of female residents were interested in a community practice (p = .024). Conclusion: While there is no evidence of differences in the volume of logged cases between genders, female surgical residents still feel that their respective gender limits their overall surgical training. Gender inequalities in training should be addressed by residency programs.


INTRASPECIFIC AGGRESSION AND ITS EFFECT ON THE DISTRIBUTION OF ANTHOPLEURA ELEGANTISSIMA AND SOME RELATED SEA ANEMONES.
Tentacle contact between genetically different individuals of the west coast sea anemone Anthopleura elegantissima initiates in one or both individuals an elaborate behavior pattern that usually results in damage to one or both animals. This aggressive behavior may be described as progressing through five stages: (1) stimulation (or initiation) during which the tentacles of the two anemones repeatedly come into contact and then withdraw from contact; (2) inflation, during which the acrorhagi commence to become turgid; (3) the movement of application, during which the inflated acrorhagi are pushed toward the source of stimulation; (4) application of ectoderm, during which damage is inflicted on the other anemone by the application of acrorhagial ectoderm to the body of the victim; and (5) recovery, during which the anemone returns to its normal posture. The tissue of the victim to which acrorhagial ectoderm has been applied by an aggressor becomes necrotic and sloughs off within a few days. Sections of such tissue that were fixed and sectioned immediately after the application of ectoderm showed penetration of the tissue of the victim by the large atrich nematocysts in the aggressor's acrorhagial ectoderm. The aggressive response of Anthopleura elegantissima is like raptorial feeding and the shell transfer behavior of some anemones in that it is a directed behavior involving asymmetrical movements that are not repeated rhythmically. Aggression resembles the swimming behavior of Stomphia and Actinostola in that the specific sequence of movements, once initiated, continues to completion in the absence of additional or continuing stimulation. The deployment of specialized effector "organs" (the acrorhagi) bearing specialized nematocysts (the large acrorhagial atrichs), the necessity for repeated contact in initiating the response, and the functioning of aggression in intraspecific territoriality are interesting characteristics of this behavior that are unique in the repertoire of anemone behavior. For Anthopleura elegantissima the aggressive response is not directly involved either in defense against predators or capture of prey. Evidence presented here suggests that for this species the aggressive response is involved in intraspecific interaction. Pertinent evidence, presented in this and a previous paper (Francis, 1973) is as follows: (1) Within clonal groups of the aggregating form of Anthopleura elegantissima the individuals are in close contact with their neighbors and the tentacles of the adjacent animals are interlaced. In the field, adjacent clones of these anemones are isolated from each other by anemone-free spaces; and in the laboratory a group of anemones of mixed clonal origins will reaggregate into isolated uniclonal groups (Francis, 1973a). (2) The specificity of the aggressive response is directly related to that shown in the segregation and separation phenomena seen both in the laboratory and in the field. Contact between clonemates does not elicit aggression and is commonly seen both in the laboratory and in the field. Contact between non-clonemates elicits aggression and is not maintained between these anemones either in the laboratory or in the field. (3) The response of the victim of an aggressive episode is such as to affect its separation from the non-clonemate aggressor. The damaged anemone may move away from the aggressor, or sometimes it may merely lean away. In the laboratory, anemones that were severely damaged as a result of repeated aggressive episodes have been observed to relase their hold on the substratum; in the field, such animals would certainly be swept away in the surf. (4) The evidence also shows that aggression does occur at the boundary between two clonal groups. In the field, anemones collected from an interclonal border showed aggression-related damage while their clonemates that were collected from the center of the clonal groups showed no such damage. In the laboratory numerous aggressive episodes were observed over a three week period as two clonal groups that had been brought into artificially close proximity interacted at their common boundary (Francis, 1973a). This suggests that aggression is important in the formation and maintenance of anemone-free zones between adjacent non-clonemates in this species. The direct effects of the aggressive behavior of A. elegantissima would be sufficient to account for clone specific segregation and at least minimal separation between clones; and although other factors, such as the activities of associated animals and the tendency of the young anemones to move apart even in the absence of the aggressive response, may be involved, the aggressive response undoubtedly functions as part of an intraspecific territorial behavior in this species. In Actinea equina also the specificity of the aggressive response correlates with the intraspecific associations apparent in the field; these anemones are solitary and they respond aggressively to contact with any other conspecific. No work has been done on the specificity of the aggressive response in Anthopleura artemisia, however these anemones do respond aggressively to contact with conspecifics, and they have not been found living in contact with genetically different conspecifics. Anthopleura xanthogrammica apparently lacks an aggressive response while having the specialized equipment (acrorhagi bearing atrich nematocysts) used in this behavior. However, the relationship between distribution and behavior is also apparent for A. xanthogrammica since genetically different members of this species are frequently found living in close contact, With the tentacles of adjacent non-clonemates passively interlaced. Taken together, this information suggests that the aggressive response of acrorhagus-bearing anemones is presently effective in intraspecific interactions. It is suggested that the evolutionary origin of the aggressive response among acrorhagus-bearing members of the family Actiniidae is monophyletic and that the behavior may have arisen in connection with competition for space either within the species of with other anthozoan species.


Nature of the low magnetization decay on stacks of second generation superconducting tapes under crossed and rotating magnetic field experiments.
The extremely low decay factor on the trapped magnetic field by stacks of second-generation high-temperature superconducting tapes reported in Appl. Phys. Lett. 104, 232602 (2014), is in apparent contradiction with the classical results for the demagnetization of superconducting bulks and thin films, where the samples undergo a severe and progressive decay under crossed magnetic field conditions. Nevertheless, in this paper, we demonstrate how the theoretical approaches and experimental measurements on superconducting bulks, thin films, and stacks of superconducting tapes can be reconciled, not only under the crossed field configuration but also under rotating magnetic field conditions, by showing that the stacks of commercial tapes behave as a system of electrically unconnected layers preventing the deformation of profiles of current along its external contour. This study extends up to the consideration of using novel superconducting/ferromagnetic metastructures, where soft ferromagnetic films are interlayered, reporting a further reduction on the magnetization decay of about 50% in the crossed field configuration. Remarkably, after applying the same number of cycles either of rotating or crossed magnetic field to these metastructures, the difference between the magnetization decay is found to be negligible, what demonstrates their highly superior performance when compared to conventional stacks of superconducting tapes.


Identification of a new HLA-B*15 allele, HLA-B*1569.
We have identified a new HLA-B*15 allele (B*1569) by polymerase chain reaction (PCR) using sequence-specific primers (SSP) and sequence-based typing (SBT). This novel allele was found in a 67-year-old white Caucasian male and differs from HLA-B*1503 at 3 positions. The nucleotide substitutions at positions 544, 559 and 560 result in amino acid changes at codon 158 from GCC (alanine) to ACC (threonine), and at codon 163 from CTG (leucine) to ACG (threonine).


Salter-Harris type-IV displaced distal radius fracture in a 5-year-old.
Displaced Salter-Harris type-IV fractures are rare in young children and can result in articular incongruity or premature physeal arrest. We describe a 5-year-old boy who sustained a displaced left distal radial Salter-Harris type-IV fracture. The patient had normal wrist function and physeal growth at the 3-year postoperative follow-up. Our patient is by far the youngest reported child with a displaced Salter-Harris type-IV fracture of the distal radius. Prompt anatomic reduction and fixation of a displaced distal radial Salter-Harris type-IV fracture can result in excellent short-term wrist motion with maintenance of physeal function.


How common is avian hybridization on an individual level?
Hybridization among different bird species is relatively common, but the hybridization rate of individuals is not well known. Justyn et al. use data from the citizen science project eBird to assess the individual hybridization rate in birds, showing that 0.064% of individuals are hybrids. The accuracy of this new estimate is affected by potential biases introduced by birdwatchers, such as over-reporting of rare hybrids and under-reporting of difficult-to-identify hybrids.


Analysis of synthetic derivatives of peptide hormones by capillary zone electrophoresis and micellar electrokinetic chromatography with ultraviolet-absorption and laser-induced fluorescence detection.
Capillary zone electrophoresis (CZE) and micellar electrokinetic chromatography (MEKC) were used for the analysis of new synthetic derivatives of hypophysis neurohormones--vasopressin and oxytocin, and pancreatic hormone--human insulin (HI) and its octapeptide fragment, derivatized by fluorescent probe, 4-chloro-7-nitrobenzo[1,2,5]oxadiazol (NBD). The suitable composition of background electrolytes (BGEs) was selected on the basis of calculated pH dependence of effective charge of analyzed peptides. Basic ionogenic peptides were analyzed by CZE in the acidic BGE composed of 100 mM H3PO4, 50 mM Tris, pH 2.25. The ionogenic peptides with fluorescent label, NBD, were analyzed in 0.5 M acetic acid, pH 2.5. The best MEKC separation of non-ionogenic peptides was achieved in alkaline BGE, 20 mM Tris, 5 mM H3PO4, with micellar pseudophase formed by 50 mM sodium dodecylsulfate (SDS), pH 8.8. Selected characteristics (noise, detectability of substance, sensitivity of detector) of the UV-absorption detectors (single wavelength detector, multiple-wavelength photodiode array detector (PDA), both of them operating at constant wavelength 206 nm) and laser-induced fluorescence (LIF) detector (excitation/emission wavelength 488/520 nm) were determined. The detectability of peptides in the single wavelength detector was 1.3-6.0 micromol dm(-3) and in the PDA detector 1.6-3.1 micromol dm(-3). The LIF detection was more sensitive, the applied concentration of NBD derivative of insulin fragment in CZE analysis with LIF detection was three orders lower than in CZE with UV-absorption detector, and the detectability of this peptide was improved to 15.8 nmol dm(-3).


[Association between volatile organic compounds and mortality risk of stroke].
Objective: To investigate the effect of volatile organic compounds (VOCs) exposure in the atmosphere on the risk of daily death from stroke in Guangzhou. Methods: Daily average concentrations of twelve atmospheric VOCs, meteorological factors, and daily deaths for stroke and its subtypes (including ischemic and hemorrhagic stroke) in Guangzhou from 2020 to 2021 were collected. The time-series Poisson generalized additive model was established to analyze the relationship between daily average concentrations of atmospheric VOCs and daily mortality from a stroke on different lag days. The season, gender, and age group further performed stratification analysis. Results: Toluene and n-pentane were associated with a higher mortality risk from stroke and its subtypes. For each interquartile range (IQR) increment in toluene concentration at lag0- 1 days, the RRs for mortality from stroke and hemorrhagic stroke were 1.060 (95%CI: 1.036-1.085) and 1.071 (95%CI: 1.030-1.113), respectively. For each IQR increment in n-pentane concentration, the RR for mortality from ischemic stroke was 1.064 (95%CI: 1.030-1.099). The effect estimates of VOCs may be higher during the cold season and among women and people aged ≥75 years. For each IQR increment in toluene concentration, the RRs for mortality risk of stroke in the cold season and women were 1.099 (95%CI: 1.056-1.143) and 1.085 (95%CI: 1.050-1.120), respectively. For n-pentane, the RR for death risk of stroke in people aged ≥75 years old was 1.072 (95%CI: 1.036-1.109). Results of sensitivity analysis showed that the effect estimates fluctuated less when PM2.5 and O3 were separately introduced for the two-pollutant model, as well as changing the degrees of freedom for covariates. Conclusions: This study suggests that VOCs may be an independent risk factor for daily mortality from stroke. Moreover, Toluene presented the most significant health impact.


Acute myocardial infarction and left bundle branch block.
Complete left bundle branch block often masks old as well as acute myocardial infarctions. However, a diagnosis of acute myocardial infarction in the presence of complete left bundle branch block can be made when the acute injury current is large enough to modify the secondary repolarization abnormalities of left bundle branch block. Under these circumstances the classical ST-T changes of an acute infarction may evolve in serial electrocardiograms.


The Importance of Inclusion for Cardiovascular Health Promotion Programs in Delaware.
Individuals with disabilities experience greater rates of cardiovascular disease than individuals without disabilities. This increase can be attributed to decreased levels of physical activity, poor eating habits, and increased levels of diabetes, smoking, and obesity. Individuals with disabilities are often excluded from surveillance, treatment, and prevention efforts. Consequently, there is little known about their participation rates in health promotion and disease prevention programs. The aims of this investigation are (1) to examine time trends in cardiovascular disease and risk factors over a 10-year period by disability status and (2) to assess the inclusiveness of health promotion programs in Delaware. The percentage of individuals with disabilities increased from 18% in 2001 to 28% in 2011. Individuals with disabilities had higher rates of cardiovascular disease (t = 80.45; degrees of freedom [df] = 198; p < .0001) and obesity (body mass index > 30 kg/m2) than individuals without disabilities (t = 33.0; df = 198; p < .0001). They also reported less physical activity (t = 44.21; df = 198; p < .0001) and worse diet quality (t = 4.70; df = 198; p < .0001). There was a consistent lack of information about inclusion and participation of individuals with disabilities in health promotion programs. Making adaptations within cardiovascular disease prevention programs in Delaware is imperative to improving the health of individuals with disabilities. Ensuring cardiovascular disease programs are accessible and provide disability-specific trained staff will reduce barriers to participation so that all individuals can benefit.


[Hodgkin's disease--immunological aspects].
The significance of immunological aspects in lymphogranulomatosis for the pathophysiological understanding of the disease was confirmed recently. Moreover, immunologic knowledge increasingly influences diagnosis, prognosis and treatment of Hodgkin's disease. In this survey cell-markers and cell-function of subpopulations of cells, participating in the disease are described. The origin of Hodgkin's- and Reed-Sternberg-cells as well as the aetiopathogenesis of the disease are discussed.


Optimizing baseline and post-concussion assessments through identification, confirmation, and equivalence of latent factor structures: findings from the NCAA-DoD CARE Consortium.
Objective: Concussion evaluations use a multidimensional assessment to evaluate unique patient function dimensions (e.g., subjective symptoms differ from balance assessments), but the overarching latent factor structure has not been empirically substantiated. Our objective was to determine the cumulative latent factor structure of pre-injury baseline and acute (<48-h) post-concussion assessment battery outcomes, and determine measurement equivalence among common factors in collegiate student-athletes. Methods: Collegiate student-athletes at baseline (n = 21,865) and post-concussion (n = 1,537) across 25-institutions completed standardized assessments. Individual items were used from the baseline and post-concussion assessments and consisted of: Sport Concussion Assessment Tool, Brief Symptom Inventory-18, Standardized Assessment of Concussion, Balance Error Scoring System, Immediate Post-Concussion Assessment and Cognitive Test, and vestibular-ocular motor screening. Exploratory factor analysis was used on half the baseline data, and confirmatory factor analysis on the remaining baseline data and post-concussion data separately. Measurement equivalence was assessed between sex, sport contact classification, concussion history, and time. Results: A 10-factor exploratory model was established and comprised of: depression, somatic, vestibulo-ocular, headache, postural stability, neurocognition, emotional, fatigue, cognitive, consciousness clouding. The 10-factor model was confirmed at baseline and post-concussion with strong measurement equivalence between timepoints. Strong to strict measurement equivalence was observed for sex, sport contact classification, and concussion history at both timepoints separately. Conclusion: Our findings established a robust 10-factor latent factor model equivalent across timepoints and common factors among healthy and concussed collegiate athletes. Clinicians can use these findings to target specific factors while reducing redundant elements to provide efficient, comprehensive post-concussion assessments.


Machine milking of Ostfriesian and Lacaune dairy sheep: udder anatomy, milk ejection and milking characteristics.
Mammary cistern anatomy derived from ultrasound measurement, milk ejection in response to exogenous oxytocin and oxytocin release and milking characteristics with and without manual prestimulation in early (months 2-4) and late (months 5-8) lactation were investigated in Lacaune and Ostfriesian dairy ewes. Vertical ultrasound cisternal cross sections of the cisternal cavities did not differ in the two breeds, whereas the cisternal area fraction located lower than the exit into the teat channel was larger in Ostfriesian than in Lacaune sheep. The cisternal area enlarged within 1 min in response to i.v. oxytocin injection, indicating milk ejection. During milking, oxytocin concentrations in Lacaune generally increased dramatically within 0.5 min from the start of prestimulation or milking, whereas only slight or no oxytocin release was detected during milking without prestimulation in Ostfriesian ewes. Prestimulation induced oxytocin release in Ostfriesian sheep within 1-2 min after the start of milking, indicating delayed response to stimulation. Two peaked milk flow curves were observed when oxytocin release and milk ejection occurred only after removal of cisternal milk. This type of milk flow was more frequent in Ostfriesian than in Lacaune ewes and was reduced in both breeds by prestimulation, while the frequency of one peaked milk flow curves increased. During the course of lactation, milk yield, main milk fraction and milk flow rates decreased, while stripping yield was almost unchanged. Although milk yield was similar in both breeds, milk flow was lower and stripping yield was higher in Ostfriesian than in Lacaune ewes. We conclude that milk ejection in ewes occurred in response to elevated oxytocin concentrations. In Ostfriesian ewes reduced and delayed oxytocin response to teat stimulation resulted in milk ejection only during stripping. Therefore, and probably because a larger volume of the cistern was located below the teat exit in the Ostfriesian breed, stripping yield was higher in Ostfriesian than in Lacaune sheep.


Arginine residues 47 and 70 of human flap endonuclease-1 are involved in DNA substrate interactions and cleavage site determination.
Flap endonuclease-1 (FEN-1) is a critical enzyme for DNA replication and repair. Intensive studies have been carried out on its structure-specific nuclease activities and biological functions in yeast cells. However, its specific interactions with DNA substrates as an initial step of catalysis are not defined. An understanding of the ability of FEN-1 to recognize and bind a flap DNA substrate is critical for the elucidation of its molecular mechanism and for the explanation of possible pathological consequences resulting from its failure to bind DNA. Using human FEN-1 in this study, we identified two positively charged amino acid residues, Arg-47 and Arg-70 in human FEN-1, as candidates responsible for substrate binding. Mutation of the Arg-70 significantly reduced flap endonuclease activity and eliminated exonuclease activity. Mutation or protonation of Arg-47 shifted cleavage sites with flap substrate and significantly reduced the exonuclease activity. We revealed that these alterations are due to the defects in DNA-protein interactions. Although the effect of the single Arg-47 mutation on binding activities is not as severe as R70A, its double mutation with Asp-181 had a synergistic effect. Furthermore the possible interaction sites of these positively charged residues with DNA substrates were discussed based on FEN-1 cleavage patterns using different substrates. Finally data were provided to indicate that the observed negative effects of a high concentration of Mg(2+) on enzymatic activity are probably due to the competition between the arginine residues and metal ions with DNA substrate since mutants were found to be less tolerant.


Studies on the energetic metabolism of Shigella flexneri and Escherichia coli hybrids devoid of penetration ability. II. Oxygen uptake and dehydrogenase activity.
Oxygen uptake and dehydrogenase activity are studied with lac+ kcpminus hybrids of Shigella flexneri, being avirulent to the eyes of guinea pigs, because of having lost ability for penetration in epithelial cells. These strains were obtained by hybridization of the virulent strain Shigella flexneri 222 5 a with the Hfr strain Escherichia coli K-12 P4x. It is established that lac+ kcp minus hybrids are characterized by significant decrease of respiratory activity. This decrease is outlined as a tendency studying O2 uptake and is extremely well expressed studying the dehydrogenase activity. The tests being performed with these hybrids show that the loss of virulence and connected with it the loss of the ability for penetration is related to a decrease of the respiratory activity of these bacteria which supply a part of the energy needed for their viability.


Energy-consistent small-core pseudopotentials for 3d-transition metals adapted to quantum Monte Carlo calculations.
We extend our recently published set of energy-consistent scalar-relativistic Hartree-Fock pseudopotentials by the 3d-transition metal elements, scandium through zinc. The pseudopotentials do not exhibit a singularity at the nucleus and are therefore suitable for quantum Monte Carlo (QMC) calculations. The pseudopotentials and the accompanying basis sets (VnZ with n=T,Q) are given in standard Gaussian representation and their parameter sets are presented. Coupled cluster, configuration interaction, and QMC studies are carried out for the scandium and titanium atoms and their oxides, demonstrating the good performance of the pseudopotentials. Even though the choice of pseudopotential form is motivated by QMC, these pseudopotentials can also be employed in other quantum chemical approaches.


A Case of Cat Scratch Disease with Neuroretinitis in a 16-Month-Old Boy.
We report a case of neuroretinitis associated with cat scratch disease (CSD) in young children. Case report. A 16-month-old boy was admitted for a detailed examination and treatment of a fever of unknown origin. Blood tests revealed no significant findings other than a white blood cell count of 16,100/mm3 and C-reactive protein level of 9.89 mg/dL. Computed tomography revealed no relevant findings to determine the causative disease. Antibiotic therapy with cefotaxime was initiated; however, the fever did not resolve. The patient was referred to our department for further examination to detect the cause of the fever. Fundoscopy revealed neuroretinitis in the right eye. His mother reported a history of breeding cats. Cat scratch disease (CSD) was suspected based on the clinical course and fundus findings. Cefotaxime was discontinued, and azithromycin, rifampicin, and prednisolone were administered, following which the fever disappeared and fundus findings improved. Immunoglobulin G (IgG) and IgM antibodies against Bartonella henselae was positive, leading to a definitive diagnosis of CSD. Infants cannot complain of decreased visual acuity; therefore, these findings may be overlooked unless a fundus examination is performed. As in this case, the early detection of neuroretinitis by an ophthalmologist may help in the diagnosis of CSD. It is extremely difficult to capture a photograph of the fundus of an infant, and recording with a smartphone is relatively simple and useful for monitoring continuous changes. Summary. We describe a case of neuroretinitis associated with cat scratch disease (CSD) that was diagnosed on the basis of fundus findings. The findings suggest the importance of an aggressive ophthalmologic examination when CSD is suspected in young children who are unable to describe their symptoms.


Radioimmunoassay of osteocalcin with polyclonal and monoclonal antibodies.
We have developed and thoroughly validated radioimmunoassays (RIAs) for osteocalcin in plasma and serum, demonstrating independence of volume and determining the recovery of added standard and within- and between-assay precision. Antibodies were raised in rabbits and mice by immunization with either osteocalcin adsorbed to polyvinylpyrrolidone or osteocalcin conjugated to bovine serum albumin. In both species, use of the conjugated osteocalcin was more efficacious. Correlation of the results obtained when groups of plasma or serum samples were analyzed by RIAs with different antibodies (two polyclonal and one monoclonal) indicated that the normal range observed for osteocalcin concentrations in serum depends on the antibody used. These findings may account for the wide range of "normal" osteocalcin values reported by different groups.


Manipulation of electron beam propagation by hetero-dimensional graphene junctions.
We demonstrate theoretically a new mechanism for the energy-selective manipulation of electron beam by nanostructured heterodimensional graphene junctions (HDGJs). Beam splitting, collimation, and beam-guide can all be realized by designing HDGJs of different dimensionality, size and orientation. Importantly, these different functions can be combined together by predesigned patterning of multiple HDGJ units in one graphene sheet, making it feasible for large-scale integration of quantum devices. Based on transport simulations, we further suggest an method to map out the electron beam propagation path through HDGJs by scanning probe microscopy.


Dentists' attitudes towards acute pharmacological pain management in children and adolescents.
This study aimed to investigate Swedish dentists' attitudes regarding pain management strategies for treating children and adolescents. It assessed recommendations for pre- and postoperative analgesics, and use of local anaesthesia, and whether application of these strategies differs between general dental practitioners (GDPs) and specialists in paediatric dentistry (SPDs). We invited all GDPs (n = 807) in southern Sweden (Region Skåne), and all registered SPDs (n = 122) working in Sweden (929 actively practising dentists under age 65 years) to participate in a postal survey on pain management in paediatric dental care. The SPDs reported using all types of pain-reducing strategies more frequently than GDPs except local anaesthesia when extracting a permanent premolar, which SPDs and GDPs used equally often. Preoperative analgesic use was greater among SPDs than GDPs. GDPs used local anaesthesia less frequently for filling therapy in primary teeth than in permanent teeth. SPDs recommend preoperative analgesics more often than GDPs do. GDPs seem to underuse local anaesthetics when treating children and adolescents. SPDs also use pain management strategies more frequently than GDPs. Among GDPs, pain management is less frequent when treating primary teeth than permanent teeth.


High-yield induction of uterine endometrial adenocarcinomas in Donryu rats by a single intra-uterine administration of N-ethyl-N'-nitro-N-nitrosoguanidine via the vagina.
A total of 130 female Donryu rats (10-week-old) were divided into two groups; 80 animals in the experimental group were given a single intra-uterine administration of 20 mg/kg N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) dissolved in polyethylene glycol (PEG) via the vagina without laparotomy, and 50 animals in the control group received PEG alone in the same manner. Small numbers of animals in both groups were killed at 3, 6, 9 and 12 months after ENNG treatment for sequential histological and endocrinological examination, and at 12.5 experimental months (15 months of age) all survivors were killed. At the termination, endometrial adenocarcinomas were present in 49% of the experimental group, compared to 0% in the control group. Severe endometrial hyperplasias were also found only in the experimental group and sequential histological examination showed first appearance of hyperplasia at 6 months and adenocarcinoma at 9 months. No tumors other than uterine carcinomas were induced by ENNG and the carcinogen treatment did not affect the endocrine environment of rats, persistent estrus appearing at 6 months after the start and increasing with age in both groups. The estradiol-17 beta:progesterone (E:P) ratio was also increased after 6 months, with further elevation at 12 months to about 8 times higher than the level at 6 months. These results indicate that an increased E:P ratio might act as a promoter of development of endometrial proliferative lesions initiated by ENNG in this rat strain. The study indicates that the present simple method using Donryu rats provides a good animal model for endometrial adenocarcinoma development in women.


Individual differences and predictors of forgetting in old age: the role of processing speed and working memory.
The goal of the present study was to examine whether individual differences in basic cognitive abilities, processing speed, and working memory, are reliable predictors of individual differences in forgetting rates in old age. The sample for the present study comprised 364 participants aged between 65 and 80 years from the Zurich Longitudinal Study on Cognitive Aging. The impact of basic cognitive abilities on forgetting was analyzed by modeling working memory and processing speed as predictors of the amount of forgetting of 27 words, which had been learned across five trials. Forgetting was measured over a 30-minute interval by using parceling and a latent change model, in which the latent difference between recall performance after five learning trials and a delayed recall was modeled. Results implied reliable individual differences in forgetting. These individual differences in forgetting were strongly related to processing speed and working memory. Moreover, an age-related effect, which was significantly stronger for forgetting than for learning, emerged even after controlling effects of processing speed and working memory.


Psychiatric syndromes in adolescent substance abusers.
Conduct disorder, major depressive episode, and the combination of attention deficit, hyperactivity, and impulse disorder were the most prevalent diagnoses after detoxification among 57 adolescents consecutively referred to an inpatient facility for treatment of substance abuse and other concurrent psychiatric disorders.


[Therapy in severe forms of pregnancy-induced arterial hypertension].
We have studied types of hemodynamics and results of arterial hypertension intensive care in 136 pregnant women in 32-38 weeks of gestation. Stroke and cardiac indexes, general peripheral vascular resistance, mean arterial pressure, cardiac work and other hemodynamic parameters were investigated by echocardiographic method. We worked out regression equations for each type of hemodynamics. Rational regimens of arterial hypertension therapy were selected according to hemodynamics types. In the hyperkinetic type a combination of propranolol with nifedipine was used, in eukinetic type--methyldopa with nifedipine and in hypokinetic type--clonidine with nifedipine. Using individualized therapy of arterial hypertension in women with gestoses we succeeded in improving the results of intensive care as a component of preparation for anesthesia in delivery ahead of time by cesarean section as well as in normal delivery at term.


[The development of higher stomatological education in the Voronejskaia oblast].
The article considers development of stomatological education in the Voronezhskaia oblast from 1920s. The issue of development of network of dental out-patient clinics in the Voronezhskaia gubernia and problem of inadequate number of dentists are considered. The organization of training courses of dentists from feldshers and paramedical personnel and training of dental personnel in dental school are presented. The role of professor A.I. Evdokimov is demonstrated related to organization of stomatological institute and training of stomatological personnel in the Voronezhskaia oblast and organization of the Voronezhskii stomatological institute. The plans of Oblzdrav of the Central'no-Chernozemnaia oblast are reflected concerning issues of training of stomatological personnel in the stomatological institute and assignment of the first stomatologists of the Voronezhskii stomatological institute. The issues are considered concerning organization of evacuation of the stomatological institute in Krasnoyarsk, joining up of parts of the four Leningradskii medical institutes and the Voronezhskii stomatological institute into the Krasnoyarskii medical institute during the Great Patriotic War and post-war restoration of teaching of stomatology at the chair of hospital surgery in the medical institute of Voronezh. The data is presented related to organization of the stomatological faculty in the Voronezhskii N.N. Burdenko medical institute, the chairs of therapeutic, orthopedic, surgical and children stomatology. The pedagogic and scientific research activity of stomatological chairs is considered, including their publication activity and international activity. The role of stomatological faculty of the Voronezhskii N.N. Burdenko state university is demonstrated.


The Role of the WI-38 Cell Strain in Saving Lives and Reducing Morbidity.
The modern success story of vaccinations involves a historical chain of events that transformed the discovery that vaccines worked, to administering them to the population. We estimate the number of lives saved and morbidity reduction associated with the discovery of the first human cell strain used for the production of licensed human virus vaccines, known as WI-38. The diseases studied include poliomyelitis, measles, mumps, rubella, varicella (chicken pox), herpes zoster, adenovirus, rabies and Hepatitis A. The number of preventable cases and deaths in the U.S. and across the globe was assessed by holding prevalence rates and disease-specific death rates constant from 1960-2015. Results indicate that the total number of cases of poliomyelitis, measles, mumps, rubella, varicella, adenovirus, rabies and hepatitis A averted or treated with WI-38 related vaccines was 198 million in the U.S. and 4.5 billion globally (720 million in Africa; 387 million in Latin America and the Caribbean; 2.7 billion in Asia; and 455 million in Europe). The total number of deaths averted from these same diseases was approximately 450,000 in the U.S., and 10.3 million globally (1.6 million in Africa; 886 thousand in Latin America and the Caribbean; 6.2 million in Asia; and 1.0 million in Europe).


Late strut fracture in a Björk-Shiley valve prosthesis (current series).
Fracture of the short strut of the latest series of Björk-Shiley mitral valve prostheses occurred 12 months after implantation. The patient died despite emergency surgery to excise and replace the prosthesis. Björk-Shiley 29-33 mm valves with a 60 degree opening angle manufactured between February 1981 and March 1982 have a predicted strut fracture rate of 0.3% (three times greater than that of valves produced outside these dates). Unimplanted valves from this batch have now been recalled by the manufacturers.


Identification of G protein-coupled receptors for Drosophila PRXamide peptides, CCAP, corazonin, and AKH supports a theory of ligand-receptor coevolution.
G-protein coupled receptors (GPCRs) are ancient, ubiquitous sensors vital to environmental and physiological signaling throughout organismal life. With the publication of the Drosophila genome, numerous "orphan" GPCRs have become available for functional analysis. Here we characterize two groups of GPCRs predicted as receptors for peptides with a C-terminal amino acid sequence motif consisting of -PRXamide (PRXa). Assuming ligand-receptor coevolution, two alternative hypotheses were constructed and tested. The insect PRXa peptides are evolutionarily related to the vertebrate peptide neuromedin U (NMU), or are related to arginine vasopressin (AVP), both of which have PRXa motifs. Seven Drosophila GPCRs related to receptors for NMU and AVP were cloned and expressed in Xenopus oocytes for functional analysis. Four Drosophila GPCRs in the NMU group (CG14575 [corrected], CG8795, CG9918, CG8784) are activated by insect PRXa pyrokinins, (-FXPRXamide), Cap2b-like peptides (-FPRXamide), or ecdysis triggering hormones (-PRXamide). Three Drosophila GPCRs in the vasopressin receptor group respond to crustacean cardioactive peptide (CCAP), corazonin, or adipokinetic hormone (AKH), none of which are PRXa peptides. These findings support a theory of coevolution for NMU and Drosophila PRXa peptides and their respective receptors.


Laboratory animal science course in Switzerland: participants' points of view and implications for organizers.
Switzerland has implemented a mandatory training in laboratory animal science since 1999; however a comprehensive assessment of its effects has never been undertaken so far. The results from the analysis of participants in the Swiss Federation of European Laboratory Animal Science Associations (FELASA) Category B compulsory courses in laboratory animal science run in 2010, 2012, 2014 and 2016 showed that the participants fully appreciated all elements of the course. The use of live animals during the course was supported and explained by six arguments characterized with cognitive, emotional and forward-looking factors. A large majority considered that the 3R (replacement, reduction and refinement) principles were adequately applied during the course. Responses to an open question offered some ideas for improvements. This overall positive picture, however, revealed divergent answers from different subpopulations in our sample (for example, scientists with more hindsight, scientists trained in biology, or participants from Asian countries).


Differential Characteristics of HMGB2 Versus HMGB1 and their Perspectives in Ovary and Prostate Cancer.
We have summarized common and differential functions of HMGB1 and HMGB2 proteins with reference to pathological processes, with a special focus on cancer. Currently, several "omic" approaches help us compare the relative expression of these 2 proteins in healthy and cancerous human specimens, as well as in a wide range of cancer-derived cell lines, or in fetal versus adult cells. Molecules that interfere with HMGB1 functions, though through different mechanisms, have been extensively tested as therapeutic agents in animal models in recent years, and their effects are summarized. The review concludes with a discussion on the perspectives of HMGB molecules as targets in prostate and ovarian cancers.


Streptococcus suis infection.
A recent outbreak of Streptococcus suis infection associated with the slaughter, preparation or consumption of pigs in Sichuan, China has led to concerns that similar outbreaks could occur in other Asian countries. Although the pig farming industry is flourishing in Taiwan, reports of S. suis infection remain rare. We report 2 cases of S. suis meningitis successfully treated with ceftriaxone and penicillin. Previous reports of S. suis infection from the English literature are reviewed and the clinical data of cases reported in Asian and European countries are summarized. In Europe, there was good correlation between clinical disease and porcine contact, while few cases in Asia reported this association. Meningitis remained the most common presentation of infection in both areas (84.6% and 75.2%, respectively), followed by sepsis (15.4% and 18.6%, respectively), which had a higher mortality rate, particularly for splenectomized patients. Other clinical presentations included enteritis, arthritis, endocarditis, pneumonia, spondylodiscitis, endophthalmitis, uveitis and peritonitis. Deafness was a distinct sequelae (50.5% in Europe and 51.9% in Asia) after recovery from S. suis infection, especially in patients with meningitis. Not all commercial identification systems for streptococci could offer adequate speciation for S. suis. When viridans group streptococci are isolated from patients with meningitis and sepsis, prompt and correct identification of isolates to the species level should be performed, especially in areas with a high prevalence of S. suis diseases.


Research progress of cathepsin B in brain aging and Alzheimer's diseases.
Cathepsin B (CatB), a cysteine protease derived from lysosomes, was initially thought to non-selectively degrade proteins from phagocytosis and autophagy in lysosomes. However, CatB has been demonstrated to selectively degrade and specifically activate target proteins, thereby regulating the process of physiological and pathological responses. The expression, enzymatic activity, and cellular localization of CatB are significantly altered in brain aging and age-related neurodegenerative diseases. Therefore, the pathological function of CatB has attracted much attention in neuroscience research. In this review, we systematically summarize the molecular functions of CatB in brain aging and Alzheimer's disease and discuss the current problems in neuropathological studies of CatB, which lay a foundation for a comprehensive understanding of the pathogenesis of aging and Alzheimer's disease.


Emodiversity evaluation of remote workers through health monitoring based on intra-day emotion sampling.
In recent years, the widespread shift from on-site to remote work has led to a decline in employees' mental health. Consequently, this transition to remote work poses several challenges for both employees and employers. To address these challenges, there is an urgent need for techniques to detect declining mental health in employees' daily lives. Emotion-based health assessment, which examines emotional diversity (emodiversity) experienced in daily life, is a possible solution. However, the feasibility of emodiversity remains unclear, especially from the perspectives of its applicability to remote workers and countries other than Europe and the United States. This study investigated the association between subjective mental health decline and emotional factors, such as emodiversity, as well as physical conditions, in remote workers in Japan. To explore this association, we conducted a consecutive 14-day prospective observational experiment on 18 Japanese remote workers. This experiment comprised pre-and post-questionnaire surveys, physiological sensing, daytime emotion self-reports, and subjective health reports at end-of-day. In daytime emotion self-reports, we introduced smartphone-based experience sampling (also known as ecological momentary assessment), which is suitable for collecting context-dependent self-reports precisely in a recall bias-less manner. For 17 eligible participants (mean ± SD, 39.1 ± 9.1 years), we evaluated whether and how the psycho-physical characteristics, including emodiversity, changed on subjective mental health-declined experimental days after analyzing descriptive statistics. Approximately half of the experimental days (46.3 ± 18.9%) were conducted under remote work conditions. Our analysis showed that physical and emotional indices significantly decreased on mental health-declined days. Especially on high anxiety and depressive days, we found that emodiversity indicators significantly decreased (global emodiversity on anxiety conditions, 0.409 ± 0.173 vs. 0.366 ± 0.143, p = 0.041), and positive emotional experiences were significantly suppressed (61.5 ± 7.7 vs. 55.5 ± 6.4, p < 0.001). Our results indicated that the concept of emodiversity can be applicable even to Japanese remote workers, whose cultural background differs from that of individuals in Europe and the United States. Emodiversity showed significant associations with emotion dysregulation-related mental health deterioration, suggesting the potential of emodiversity as useful indicators in managing such mental health deterioration among remote workers.


Direct beneficial effect of insulin on blood rheological disorders in the microcirculation.
Under both the in vivo and in vitro conditions we investigated the insulin effect on the most significant factor disturbing the blood rheological disorders in the microcirculation, the red blood cell aggregability. The in vivo studies we carried out in the 42 insulin treated diabetic patients (diabetes mellitus type II), as well as conducted the in vitro investigations of the blood both of the diabetic patients (24) and of the healthy people (20) where the insulin was added to the blood ex vivo. The RBC aggregability in blood investigated with the "Georgian technique" was found significantly enhanced, by about 100 per cents in the diabetic patients. Under the in vivo conditions insulin administered intravenously decreased the RBC aggregability almost to the normal level in diabetic patients. In addition, in the in vitro studies we found that the insulin lowered significantly the RBC aggregability when it was significantly enhanced by addition of Dextran-500, as well as in the blood of patients with the ischemic brain infarcts. The decreasing effect on the RBC aggregability was observed even in the healthy control group where the RBC aggregability was in a normal range.


Familial gastrointestinal stromal tumors associated with dysphagia and novel type germline mutation of KIT gene.
A family with multiple gastrointestinal stromal tumors (GISTs), a new type of germline mutation of KIT gene, and dysphagia is reported. The mutation was observed at Asp-820 in tyrosine kinase (TK) II domain. Mutations in TK II domain have been found in mast cell and germ cell tumors but not in GISTs, and the present family members are the first reported cases of GISTs with TK II domain mutations, including sporadic GISTs. Because interleukin 3-dependent Ba/F3 murine lymphoid cells transfected with the mutant KIT complementary DNA grew autonomously without any growth factors and formed tumors in nude mice, the mutation was considered to be gain-of-function type. Family members with the germline KIT mutation reported dysphagia, but those without the mutation did not. The mechanism of dysphagia was examined with gastrointestinal fiberscopy, endoscopic ultrasonography, and esophageal manometry. No mechanical obstruction was found, and the esophagus was not remarkably dilated. In the family members with dysphagia, endoscopic ultrasonography at the esophagocardiac junction showed a thickened hyperechoic layer between the circular and longitudinal muscle layers, suggesting hyperplasia of interstitial cells of Cajal at the myenteric plexus layer. Manometry showed low resting lower esophageal sphincter pressure and abnormal simultaneous contractions of the esophagus without normal peristalsis. These findings indicate that the dysphagia of the present family is different from typical achalasia. This is the first report of familial dysphagia caused by germline gain-of-function mutation of the KIT gene at the TK II domain.


Expression of Asn-d-Trp-Phe-NH2 in the brain of the terrestrial slug Limax valentianus.
The tripeptide Asn-d-Trp-Phe-NH(2) (NdWFamide) is a D-amino acid-containing cardioexcitatory peptide initially isolated from Aplysia. Previously we detected NdWFamide immunoreactivity in the visceral giant cells, the largest neurons in the brain of the terrestrial slug Limax located at the dorsal surface of the visceral ganglia. In the present study, we further analyzed the morphological features of these neurons by an intracellular injection of Lucifer yellow, and found that these neurons extend neurites out of the brain through at least 5 nerve bundles. We then isolated a gene and a cDNA clone potentially encoding a NdWFamide precursor, and investigated expression at the levels of mRNA and protein in Limax. The NdWFamide gene consists of 5 exons spanning at least 17 kb of the genome, and its open reading frame extends over 3 exons. The spatial expression pattern of NdWFamide mRNA was almost identical to that of the NdWFamide peptide, with some minor discrepancies in between. Although the most remarkable expression was evident in the visceral giant cells, we also found the expression of NdWFamide mRNA and peptide in the cerebral and pedal ganglia. These results suggest the involvement of NdWFamide in the regulation of a broad area of the slug's body.


[Results of screening for hearing disorders using the Ewing test].
Late developments support that deaf children have an urgent need for rehabilitation and hence for early search for hearing defects. One of the modalities to achieve this goal is mass screening of populations. In Belgium the long established well-baby-clinics provide a commodity for these programs. As most infants attend regularly these clinics, it was evident to perform here the testing procedure. The Ewing-test was chosen as the tool for the screening. We started about 1980. In this discussion the statistics from 1984 to 1986 from one province (West-Vlaanderen) are used. It appeared that approximately 60% of the 9-month old children are screened. After two failures these children are referred to their family doctor. About 1% of the children tested have a diagnostic examination. In this group we found a lot of children with middle ear problems. Although the screening was not set up to detect these children, we think it is useful that they come under medical control. A special program was started to see if the sensitivity of the test was good. Till now we could not find any case of a deaf child that did not fail the Ewing-test.


Utilizing flat-panel detector parenchymal blood volume imaging (FD-PBV) for quantitative kidney perfusion analysis during the process of percutaneous transluminal renal angioplasty (PTRA): A case report.
Traditional digital subtraction angiography (DSA) provides lumen morphology of renal artery as indicators for vascular patency in patients with renal artery stenosis (RAS). It, however, lacks hemodynamic information toward target kidney. To solve this shortcoming, a novel technique, flat-panel detector parenchymal blood volume imaging (FD-PBV), is introduced, which is able to evaluate hemodynamic changes of target kidney intraoperatively. A 77-year-old female presented with hypertension, intermittent dizziness, nausea, and fatigue. Ninety-nine percent stenosis of left RAS was found. Percutaneous transluminal renal angioplasty was performed, along with FD-PBV acquisition protocol. Her symptoms relieved gradually after procedure. Intuitive FD-PBV maps showed her renal perfusion improved remarkably. Quantitative analysis of FD-PBV showed her kidney volume was 47.02 and 75.61 cm with average density of contrast medium (CM) 58.1 HU and 311.5 HU before and after stenting. Follow-up at 6 months showed patency of the stent and stable kidney blood perfusion. FD-PBV technique possesses a remarkable value in quantitatively assessing the changes of kidney blood perfusion and can be a useful auxiliary technique for DSA.


Mechanical properties of human tendon and their age dependence.
There are no previously published data on changes in the mechanical behaviors of human tendon from maturation in the second decade to senectitude in the seventh decade or thereafter. In this study, 44 tendons from individuals ranging in age from 16 to 88 yr were subjected to an extensive series of mechanical tests which included preconditioning, extensions at strain rates of 100 percent/s, 1 percent/s, and 0.01 percent/s, and stress relaxation with cyclic and constant extensions. Pairs of extensions at 1 percent/s were run throughout the protocol to evaluate the repeatability of tissue response. It was found that these responses changed little for any single sample within a pair of such tests; however, throughout the protocol, the peak stresses and moduli decreased. Extensions at different rates revealed a definite rate dependency of tendon responses with sample modulus being directly related to extension rate and slightly less hysteresis at 1 percent/s than at 100 percent/s or 0.01 percent/s. The load relaxation in samples subjected to either cyclic or constant extensions was generally best described by a linear function of the logarithm of time. The rate of relaxation with constant extension varied little with extension magnitude. The rate of relaxation in the cyclic tests was greater at 10 Hz than at 0.1 Hz. The results indicate that subject age has no effect on tendon modulus and a very small effect on hysteresis and relaxation. Extensive information on subject history was not available in this study for correlation with mechanical responses so that an age effect may have been masked by other variables, possibly health, diet, disease, or exercise.


Sustainable Alternatives for the Development of Thermoset Composites with Low Environmental Impact.
The current concerns of both society and the materials industries about the environmental impact of thermoset composites, as well as new legislation, have led the scientific sector to search for more sustainable alternatives to reduce the environmental impact of thermoset composites. Until now, to a large extent, sustainable reinforcements have been used to manufacture more sustainable composites and thus contribute to the reduction of pollutants. However, in recent years, new alternatives have been developed, such as thermosetting resins with bio-based content and/or systems such as recyclable amines and vitrimers that enable recycling/reuse. Throughout this review, some new bio-based thermoset systems as well as new recyclable systems and sustainable reinforcements are described, and a brief overview of the biocomposites market and its impact is shown. By way of conclusion, it should be noted that although significant improvements have been achieved, other alternatives ought to be researched.