The Prevalence of Suicidal Behavior in Autism Spectrum Disorder.
Background: Suicidal ideation (SI) and suicide attempts (SA) are common in autistic individuals, but prevalence rates have not yet been estimated with meta-analysis. Aims: This meta-analysis aims to estimate SI and SA prevalence rates in autistic individuals and identify subgroup differences based on sample characteristics and study quality. Methods: A systematic search identified 52 studies with 88,509 autistic participants reporting SI and SA. Pooled prevalence estimates were calculated using a random-effects model. Results: Pooled prevalence estimates of lifetime SI and SA were 37.2% [95% CI 25.3-50.8] and 15.3% [95% CI 9.5-23.6], respectively. For 12-month prevalence, this was 25.4% [95% CI 19.0-33.2] and 14.1% [95% CI 7.4-25.2], respectively. Subgroup analyses revealed significant differences based on age (SI), region (SI), data collection (SI), measurement scales used to define autism and suicidality (SA), and representation of the study sample (SI and SA). Heterogeneity measures were high for all outcomes (I2 = 60.3-99.1%). Limitations: The heterogeneity of the included studies may limit the generalizability of our findings. Conclusion: The high rates of suicidal problems in autistic individuals call for a systematic evaluation of suicidality in clinical practice and adequate therapeutic interventions to improve this condition.


An overview of administrative and national survey databases for use in otolaryngology research.
An emerging focus on measurement and reporting of health care quality indicators calls for a sound evidence base that otolaryngologists can use to support clinical care decisions. In addition to traditional clinical trials, practitioners are heeding results of high-quality comparative-effectiveness and health services research analyses to better understand the complexity of disease epidemiology, care variation, health care costs, and surgical utilization for common conditions. Many national publicly available data sources exist for use in clinical research that may be of benefit for the academic and clinical otolaryngologist. The strength and value of these sources vary depending on the intended use or research question. The purpose of this commentary is to introduce and provide an overview of some major national and administrative databases, highlight potential strengths and limitations of these data, and suggest applications for use in advancing the care of our patients in otolaryngology.


Projected Future Vegetation Changes for the Northwest United States and Southwest Canada at a Fine Spatial Resolution Using a Dynamic Global Vegetation Model.
Future climate change may significantly alter the distributions of many plant taxa. The effects of climate change may be particularly large in mountainous regions where climate can vary significantly with elevation. Understanding potential future vegetation changes in these regions requires methods that can resolve vegetation responses to climate change at fine spatial resolutions. We used LPJ, a dynamic global vegetation model, to assess potential future vegetation changes for a large topographically complex area of the northwest United States and southwest Canada (38.0-58.0°N latitude by 136.6-103.0°W longitude). LPJ is a process-based vegetation model that mechanistically simulates the effect of changing climate and atmospheric CO2 concentrations on vegetation. It was developed and has been mostly applied at spatial resolutions of 10-minutes or coarser. In this study, we used LPJ at a 30-second (~1-km) spatial resolution to simulate potential vegetation changes for 2070-2099. LPJ was run using downscaled future climate simulations from five coupled atmosphere-ocean general circulation models (CCSM3, CGCM3.1(T47), GISS-ER, MIROC3.2(medres), UKMO-HadCM3) produced using the A2 greenhouse gases emissions scenario. Under projected future climate and atmospheric CO2 concentrations, the simulated vegetation changes result in the contraction of alpine, shrub-steppe, and xeric shrub vegetation across the study area and the expansion of woodland and forest vegetation. Large areas of maritime cool forest and cold forest are simulated to persist under projected future conditions. The fine spatial-scale vegetation simulations resolve patterns of vegetation change that are not visible at coarser resolutions and these fine-scale patterns are particularly important for understanding potential future vegetation changes in topographically complex areas.


A comparison between two full-scale MBR and CAS municipal wastewater treatment plants: techno-economic-environmental assessment.
A holistic assessment procedure has been used in this study for comparing conventional activated sludge (CAS) and membrane bioreactor (MBR) processes for the treatment of municipal wastewater. Technical, social, administrative, economic and environmental impacts have been evaluated based on 1 year of operational data from three full-scale lines (one MBR and two CAS) working in parallel in a large municipal treatment plant. The comparative assessment evidences a slight advantage of the conventional process in the studied case, essentially due to lower costs, complexity and energy consumption. On the other hand, the MBR technology has a better social acceptance and similar overall environmental footprint. Although these results are influenced by site-specific parameters and cannot be generalized, the assessment procedure allowed identifying the most important factors affecting the final scores for each technology and the main differences between the compared technologies. Local conditions can affect the relative importance of the assessed impacts, and the use of weighting factors is proposed for better tailoring the comparative assessment to the local needs and circumstances. A sensitivity analysis on the weighted final scores demonstrated how local factors are very important and must be carefully evaluated in the decision making process.


Clinical pharmacokinetics of linezolid, a novel oxazolidinone antibacterial.
Linezolid is the first antibacterial to be approved from the oxazolidinone class. The drug has substantial antimicrobial activity against Gram-positive organisms such as streptococci, staphylococci and enterococci, including species resistant to conventional antibacterial treatment. Linezolid is fully bioavailable following oral administration when compared with intravenous administration. Maximum plasma linezolid concentrations are usually achieved between 1 and 2 hours after oral administration. Food slightly decreases the rate, but not the extent, of absorption. The distribution of linezolid is approximately equivalent to total body water, and there is low protein binding (31%) to serum albumin. The elimination half-life of linezolid is 5-7 hours, and twice-daily administration of 400-600 mg provides steady-state concentrations in the therapeutic range. Linezolid is mainly cleared by non-renal clearance to two metabolites and renal clearance of the parent compound. Approximately 50% of an administered dose appears in the urine as the two major metabolites, and approximately 35% appears as parent drug. A small degree of nonlinearity has been observed, with a 30% decrease in clearance after a 5-fold increase in dose. The nonlinearity is not relevant over the therapeutic dosage range. Plasma linezolid concentrations in elderly patients, patients with mild to moderate hepatic impairment or mild to severe renal impairment are similar to those achieved in young or healthy volunteers. Higher concentrations are observed in women as compared with men, but the difference is not sufficient to warrant an adjustment in dosage. In patients with severe renal impairment requiring haemodialysis, the exposure to the two primary metabolites was 7 to 8-fold higher than in patients with normal renal function. Therefore, linezolid should be used with caution in patients with severe renal insufficiency. A higher clearance of linezolid was found in children as compared with adults, and therefore higher daily dosages per kg bodyweight are required in children. There is no pharmacokinetic interaction when linezolid is coadministered with aztreonam, gentamicin or warfarin. Linezolid is a mild, reversible, inhibitor of monoamine oxidases A and B. Coadministration of linezolid with the adrenergic agents pseudoephedrine and phenylpropanolamine resulted in increases in blood pressure relative to these agents alone or to placebo. The degree of the change in blood pressure was within that associated with normal daily activities. No interaction was observed when linezolid was coadministered with the serotonergic agent dextromethorphan.


Effect of peritoneal fluid from endometriosis patients on sperm motion characteristics and acrosome reaction.
To determine whether peritoneal fluid from women with endometriosis contributes to infertility by impairing sperm motion and functional characteristics. Women with endometriosis (n = 20) underwent laparoscopy for infertility or pelvic pain. Patients undergoing tubal ligation served as controls (n = 14). Peritoneal fluid was aspirated from women with endometriosis, or from women undergoing laparoscopic tubal ligation. Sperm motility, motion characteristics and acrosome reaction were assessed following incubation with peritoneal fluid. Sperm motility, motion characteristics, and acrosome reaction did not differ significantly between the two groups after 3, 5, or 24 hours of incubation with peritoneal fluid. Sperm motion or functional characteristics showed no significant impairment when sperm from normal donors were incubated with peritoneal fluid from patients with endometriosis. It is unlikely that peritoneal fluid in these patients contributes to infertility.


Psychosocial work stressors as antecedents of musculoskeletal problems: a systematic review and meta-analysis of stability-adjusted longitudinal studies.
Although the relationship between psychosocial workplace conditions and musculoskeletal problems has been extensively studied, the causal impact of psychosocial workplace factors in the development of musculoskeletal problems remains unclear. The purpose of the present study was to conduct a systematic review of baseline-adjusted prospective longitudinal studies estimating the lagged effect of psychosocial risk factors on musculoskeletal problems in industrialized work settings. A literature review was conducted by searching the MEDLINE, EMBASE, and PsychINFO databases dated until August 2009. The authors classified studies into categories of psychological work stressors and musculoskeletal problems. Available effect sizes were converted to odds ratios (OR). ORs were then pooled for each stressor-problem relationship using a random-effects model. Additionally, the possibility of publication bias was assessed with the Duval and Tweedie nonparametric "trim and fill" procedure. In total, 50 primary studies fulfilled inclusion criteria. Within these studies at least five effect sizes were available for 23 of the 45 possible psychosocial work stress-musculoskeletal problems relationships, leaving 9 psychosocial variables and four musculoskeletal problem areas for analyses. Of these 23 relationships, pooled OR estimates were positive and significant ranging from 1.15 to 1.66 with the largest pooled OR estimating the relationship between highly monotonous work and lower back pain. The lagged effect of low social support on lower limb problems was the only effect size for which the statistical test for bias was significant. Most psychosocial stressors had small but significant lagged effects on the development of musculoskeletal problems. Thus, organizational interventions to minimize these stressors may be promising in reducing one risk factor for the development of employee musculoskeletal problems.


[Innovations in education for the digital student].
A significant percentage of today's teaching staff received their professional training before the revolution in information and communication technology took place. Students, by contrast, are so-called 'digital natives': they grew up surrounded by digital technology. Present day students are used to multi-tasking and expect to be facilitated in using educationalfacilities regardless of time and place. Adapting higher education to present day students' study behaviour and expectations requires reconsideration of educationalform and methods. Several types of staff can be distinguished in their attitude towards technological innovation in education. Among them are staff who are reluctant in accepting innovations. Dental schools face the challenge of finding supportfor innovations with all their teaching staff and to better adapt to the twenty-first century student. In order to introduce technological innovations successfully, students need to become involved and sufficient attention must be paid to qualifying instructors.


Bronchodilating activity of broxaterol transdermal patch and its protective effect on bronchial constriction induced by inhaled distilled water mist.
The bronchodilating activity and the ability of broxaterol transdermal patch to inhibit bronchial constriction in response to distilled water mist (UNH2O) inhalation were assessed. The study was performed in 10 asthmatic patients in clinical remission according to a placebo-controlled, double-blind, randomized crossover design. Test medications were broxaterol patch (size = 1.75 cm2; programmed delivery = 105 mcg/h) and a matched placebo patch. A spirometric examination was performed before patch application (at 8:30-9:00 a.m.) and 24 hours later. Immediately afterwards, the UNH2O inhalation test was made, consisting of 3 bronchial exposures lasting 30, 60 and 120 s respectively with 3-minute intervals between challenges. Immediately after each exposure, a spirometric examination and specific airway resistance measurements were made. The results obtained show that broxaterol patch exerts a statistically significant bronchodilating effect and has a better protective effect than placebo patch on UNH2O-induced bronchial constriction. The local tolerability of patches was very good. Slight tremors were observed in some subjects.


Leukocyte-endothelial interactions: clinical trials of anti-adhesion therapy.
This review describes efforts to develop therapies directed at leukocyte and endothelial adhesion molecules for the treatment of acute and chronic inflammatory diseases, including hemorrhagic shock. Published research and review articles and Web sites relating to the clinical use of drugs directed to leukocyte or endothelial cell adhesion molecules. The results of relevant studies of adhesion blockade are reviewed. Trials in putative clinical ischemia-reperfusion disorders, particularly traumatic shock, are emphasized. Trials are designated as positive or negative, depending on whether the primary end points established by the trial investigators were met. Blockade of leukocyte adhesion to endothelium by monoclonal antibodies or other antagonists has been demonstrated to reduce vascular and tissue injury in a wide variety of animal models of inflammatory and immune disease. Anti-adhesion therapy directed at lymphocyte trafficking has shown efficacy in several phase 2 and 3 clinical trials in inflammatory bowel disease, multiple sclerosis, and psoriasis. Despite strong preclinical data, results of phase 2 and 3 trials of neutrophil adhesion blockade in putative ischemia-reperfusion disorders-stroke, myocardial infarction, and hemorrhagic shock-have been disappointing.


[Isolated paralysis of the ramus marginalis mandibulae nervi facialis: clinical aspects, etiology, diagnosis and therapy. An overview].
Disorders of lower lip in facial expression are mostly caused by functional impairment of the marginal mandibular branch of the facial nerve. In a typical case, active exposure of the incisors of the mandible is not possible and the lip appears distorted towards the healthy side. The most frequent cause of a lesion of the marginal mandibular branch is iatrogenic injury during operations in the mandibular or parotid region. Functional disorders of the platysma, congenital hypoplasia or aplasia of the lower lip muscles, and defective healing following facial palsy may lead to a similar disorder which, however, must be differentiated from an isolated paralysis of the marginal mandibular branch. In addition to inactivation of the nerve branch on the opposite side, several surgical procedures have been described to achieve not only aesthetic, but also functional rehabilitation of lower lip expression. The present review gives an overview on the causes, clinical appearance, diagnosis, differential diagnosis, and therapy of unilateral isolated paresis of the marginal mandibular branch of the facial nerve.


Testicular seminoma associated with massive necrosis.
A 70-year-old man presented with 2 years history of a painless hard mass in the left scrotum. Both pelvic computed tomography and magnetic resonance image showed enhancement only in the wall of the tumor, indicating a benign disease, rather than a neoplastic lesion. Physical examination 3 weeks after the first presentation showed the remarkable reduction of the left testicular size. Left inguinal orchiectomy was carried out and pathological diagnosis was seminoma with extensive necrotic areas occupying mostly the tumor. Either shrinkage or enlargement of testicular size with a long history demands full investigation for malignancy.


Distinct beneficial effects of continuous vs accumulated exercise training on cardiovascular risk factors in Wistar rats.
We compared the effects of continuous exercise (CE) vs accumulated exercise (AE) training on CVD risk factors and heart of young male Wistar rats. The exercise training (ET) was performed in a swimming pool for 30-60 min/day, 5 days/week over 15 weeks. CE group performed the ET in a single long daily session (30-60 min), while AE group performed the ET at the same frequency, intensity, and duration of CE rats, but in three short bouts over the course of a day (10-20 min in three daily sessions). AE training was more efficient than CE in attenuating body and fat weight gain and inhibiting visceral adipocyte hypertrophy at the same food intake level. CE training was more efficient in improving systolic blood pressure, LDL/HDL cholesterol, and serum triglyceride. Both ET protocols increased heart function, decreased lipid peroxidation, and increased intracellular Hsp72 content in the heart. This work shows distinct beneficial effects of CE vs AE training suggesting that the prescription of one or other may be preferred to prevent the increase of a specific CVD risk factor.


Improvement of skin lesions in corticosteroid withdrawal-associated severe eczema by multicomponent traditional Chinese medicine therapy.
We recently showed that multicomponent traditional Chinese medicine (TCM) therapy had steroid-sparing effects in moderate-to-severe eczema. We sought to evaluate TCM effects in severe eczema in a 7-year-old male with refractory disease and corticosteroid withdrawal syndrome. Prior to referral, the patient had been treated since infancy with increasingly intensive standard of care, including high-dose topical and systemic corticosteroid and antibiotic therapy and was unable to tolerate further steroid treatment. The patient was administered a combination of oral and topical TCM for 17 months following discontinuation of his steroid regimen. His overall medical condition was assessed by SCORAD criteria and laboratory evaluations of serum IgE, absolute eosinophil count, and liver and kidney function tests. The patient showed rapid improvement of clinical measures of disease after starting TCM therapy, with marked improvement of sleep quality within the first week, complete resolution of itching, oozing, and erythema at 2 weeks, and a 79% and 99% decrease in his SCORAD values after one month and 3-6 months of TCM, respectively. Serum total IgE decreased by 75% (from 19,000 to 4630 (kIU/L), and absolute eosinophil counts decreased by 60% (from 1000 to 427 cells/μL) after 12 months of treatment. The patient did not require oral or topical steroids during the 17-month trial of TCM. TCM was tapered without complications. His dermatologic manifestations continued to be well-controlled 3 months after discontinuation. This case study suggests TCM should be further evaluated in controlled clinical studies of patients with severe, refractory eczema and steroid withdrawal syndrome.


[Protein Z is not an endonuclease of the recF recombination pathway in Escherichia coli K12].
A 74 kD protein was extracted from Escherichia coli cells and purified under the physiological conditions. The protein is able to catalyze the reactions of endonucleolytic degradation of plasmid DNA. The genetic determinant coding for the 74 KD protein synthesis has been localized between 17 and 27 min on Escherichia coli chromosomal map. The endonuclease previously described as a recF gene dependent "protein Z" (Krivonogov S. V., Novitskaja V. A. Mol. Gen. Genet., 1982, v, 187, p. 302) is shown to be independent of the integrity of Escherichia coli recF gene.


Dual orexin receptor antagonists show distinct effects on locomotor performance, ethanol interaction and sleep architecture relative to gamma-aminobutyric acid-A receptor modulators.
Dual orexin receptor antagonists (DORAs) are a potential treatment for insomnia that function by blocking both the orexin 1 and orexin 2 receptors. The objective of the current study was to further confirm the impact of therapeutic mechanisms targeting insomnia on locomotor coordination and ethanol interaction using DORAs and gamma-aminobutyric acid (GABA)-A receptor modulators of distinct chemical structure and pharmacological properties in the context of sleep-promoting potential. The current study compared rat motor co-ordination after administration of DORAs, DORA-12 and almorexant, and GABA-A receptor modulators, zolpidem, eszopiclone, and diazepam, alone or each in combination with ethanol. Motor performance was assessed by measuring time spent walking on a rotarod apparatus. Zolpidem, eszopiclone and diazepam [0.3-30 mg/kg administered orally (PO)] impaired rotarod performance in a dose-dependent manner. Furthermore, all three GABA-A receptor modulators potentiated ethanol- (0.25-1.5 g/kg) induced impairment on the rotarod. By contrast, neither DORA-12 (10-100 mg/kg, PO) nor almorexant (30-300 mg/kg, PO) impaired motor performance alone or in combination with ethanol. In addition, distinct differences in sleep architecture were observed between ethanol, GABA-A receptor modulators (zolpidem, eszopiclone, and diazepam) and DORA-12 in electroencephalogram studies in rats. These findings provide further evidence that orexin receptor antagonists have an improved motor side-effect profile compared with currently available sleep-promoting agents based on preclinical data and strengthen the rationale for further evaluation of these agents in clinical development.


Postsynaptic density radiation signature following space irradiation.
Introduction: The response of the brain to space radiation is an important concern for astronauts during space missions. Therefore, we assessed the response of the brain to 28Si ion irradiation (600 MeV/n), a heavy ion present in the space environment, on cognitive performance and whether the response is associated with altered DNA methylation in the hippocampus, a brain area important for cognitive performance. Methods: We determined the effects of 28Si ion irradiation on object recognition, 6-month-old mice irradiated with 28Si ions (600 MeV/n, 0.3, 0.6, and 0.9 Gy) and cognitively tested two weeks later. In addition, we determined if those effects were associated with alterations in hippocampal networks and/or hippocampal DNA methylation. Results: At 0.3 Gy, but not at 0.6 Gy or 0.9 Gy, 28Si ion irradiation impaired cognition that correlated with altered gene expression and 5 hmC profiles that mapped to specific gene ontology pathways. Comparing hippocampal DNA hydroxymethylation following proton, 56Fe ion, and 28Si ion irradiation revealed a general space radiation synaptic signature with 45 genes that are associated with profound phenotypes. The most significant categories were glutamatergic synapse and postsynaptic density. Discussion: The brain's response to space irradiation involves novel excitatory synapse and postsynaptic remodeling.


Bisphenol a diglycidyl ether (BADGE) suppresses tumor necrosis factor-alpha production as a PPARgamma agonist in the murine macrophage-like cell line, RAW 264.7.
Bisphenol A diglycidyl ether (BADGE) is a newly described peroxisome proliferator-activated receptor gamma (PPARgamma) antagonist in adipogenic cells. In contrast, in the macrophage-like cell line RAW 264.7, BADGE, like the PPARgamma agonist pioglitazone hydrochloride, not only increased promoter activity of the PPARgamma-luciferase reporter gene, but also suppressed lipopolysaccharide (LPS)-induced tumor necrosis factor-alpha (TNF-alpha) production. These results suggest that BADGE is a PPARgamma agonist in RAW 264.7 cells. Furthermore, overexpression of the coactivator p300 restored BADGE- or pioglitazone hydrochloride-suppressed promoter activity of the nuclear factor-kappa B (NF-kappaB)-luciferase reporter gene, suggesting that PPARgamma may interfere with NF-kappaB transcriptional activity via coactivator competition.


Attenuation of positive and negative affect in men and women at increased risk for hypertension: a function of endogenous barostimulation?
We hypothesized that activation of endogenous baroreflexes would be associated with reduced responsivity to affective stimuli and that this effect would be enhanced in individuals at risk for hypertension. Images from the International Affective Picture System were presented during systolic and diastolic phases of the cardiac cycle. Affective responsivity was measured using electromyographic activity, skin conductance, and ratings of arousal and valence. Compared to offspring of normotensives, individuals with a parental history of hypertension showed reduced responsivity to both positive and negative affective stimuli; however, responsivity did not differ as a function of cardiac cycle phase. Although these findings do not support a barostimulation mechanism of affective dampening, it is premature to discount the baroreflex inhibition hypothesis given the limited affective reactions elicited by visual stimuli presented in the laboratory.


Duodenal metastasis from hepatocelluar carcinoma demonstrated on FDG PET/CT imaging.
It is rare for patients with hepatocellular carcinoma (HCC) to have gastrointestinal metastasis. We report on a 67-year-old man with HCC who was first treated with liver transplantation and then received transcatheter arterial embolization for recurrence in the right hepatic lobe. He underwent whole-body FDG PET/CT imaging for survey, and a FDG-avid lesion was localized in the duodenum. Endoscopic examination revealed an ulcerative tumor in the first portion of the duodenum. Histologic examination determined metastatic HCC.


Falls and EQ-5D rated quality of life in community-dwelling seniors with concurrent chronic diseases: a cross-sectional study.
Although recommended for use in studies investigating falls in the elderly, the European Quality of Life Group instrument, EQ-5D, has not been widely used to assess the impact of falls on quality of life. The aim of this study was to investigate the association of single and frequent falls with EQ-5D rated quality of life in a sample of German community-dwelling seniors in primary care suffering a variety of concurrent chronic diseases and conditions. In a cross-sectional study, a sample of community-dwelling seniors aged ≥ 72 years was interviewed by means of a standardised telephone interview. According to the number of self-reported falls within twelve months prior to interview, participants were categorised into one of three fall categories: no fall vs. one fall vs. two or more falls within twelve months. EQ-5D values as well as other characteristics were compared across the fall categories. Adjustments for a variety of concurrent chronic diseases and conditions and further variables were made by using multiple linear regression analysis, with EQ-5D being the target variable. In total, 1,792 participants (median age 77 years; 53% female) were analysed. The EQ-5D differed between fall categories. Participants reporting no fall had a mean EQ-5D score of 81.1 (standard deviation [s.d.]: 15.4, median: 78.3), while participants reporting one fall (n = 265; 14.8%) and participants with two or more falls (n = 117; 6.5%) had mean total scores of 77.0 (s.d.: 15.8, median: 78.3; mean difference to participants without a fall: -4.1, p < 0.05) and 72.1 (s.d.: 17.6, median: 72.5; mean difference: -9.0, p < 0.05), respectively. The mean difference between participants with one fall and participants with two or more falls was -4.9 (p < 0.05). Under adjustment for a variety of chronic diseases and conditions, the mean decrease in the total EQ-5D score was about -1.0 score point for one fall and about -2.5 points for two or more falls within twelve months. In quantity, this decrease is comparable to other chronic diseases adjusted for. Among the variables with the greatest negative association with EQ-5D ratings in multivariate analysis were depression and fear of falling. The findings suggest that falls are negatively associated with EQ-5D rated quality of life independent of a variety of chronic diseases and conditions.


Prevention of ventilator-associated pneumonia: what nurses can do.
Ventilator-associated pneumonia is the second most common hospital-acquired infection in medical intensive care units in the United States. Prevention of ventilator-associated pneumonia must be regarded as one of the most important issues in critical care and it has already become one of the core intensive care unit performance measures proposed by the Intensive Care Advisory Panel of the Joint Commission on Accreditation of Healthcare Organizations. This article focuses on prevention strategies which can be applied by critical care nurses during daily care.


Computer designed and milled porcelain esthetic resin-bonded fixed partial denture.
A promising method of fabricating porcelain esthetic resin-bonded pontics is proposed. CAD-CAM crown software in the CEREC system is edited and modified to mill the replacement for a missing lower incisor out of a block of porcelain.


Preparation, Purification, and Identification of a Monoclonal Antibody Against NRP2 b1b2 Domain.
First identified as a high-affinity kinase-deficient receptor for class-3 semaphorins and vascular endothelial growth factor (VEGF) families, Neuropilin2 (NRP2) is a transmembrane non-tyrosine-kinase glycoprotein that has a vital function in neuronal patterning. Furthermore, NRP2 expression is often upregulated in cancer tissues and correlated with poor prognosis. In the present study, we report the establishment of a monoclonal antibody specific for NRP2b1b2 domain (NRP2 MAb) through hybridoma method. NRP2 MAb is measured to have a titer of 5.12 × 10(5) against NRP2b1b2 in indirect ELISA. Western blotting, flow cytometry, and immunofluorescence analysis indicate that NRP2 MAb can combine full-length NRP2 in LoVo and SW480 cells. Besides helping further understand NRP2-related pathological mechanisms and cell-signaling pathways, NRP2 MAb may act as a therapeutic agent for cancer in the future.


Xanthogranulomatous pyelonephritis--the "great imitator" justifies its name.
A case of focal xanthogranulomatous pyelonephritis (XGP) clearly imitating renal tumour is presented. The authors underline the need to include focal XGP in the preoperative differential diagnosis of a renal mass even in the absence of typical characteristics.


[Does robotic radical cystectomy affect oncological outcomes in bladder cancer patients?]
Robot-assisted surgery in urology is now being used in a wide range of procedures. In addition to reconstructive procedures, tumour surgery such as radical cystectomy is of particular importance. While studies on the perioperative quality of robotic-assisted radical cystectomy suggest a favorable impact on morbidity (and thus mortality), the question remains as to what extent the oncological quality is influenced by this procedure in terms of recurrence-free and overall survival.In this context, following a comprehensive literature review, this paper presents data from retrospective cohort comparisons of open and robotic cystectomy, registry data and single centre series on robotic and open cystectomy, and the results of prospective randomised trials.In summary, from an oncological point of view, robotic cystectomy is not inferior to open cystectomy. Overall survival, cancer-specific survival, and progression-free survival data do not differ in retrospective cohort studies, in indirect comparisons of registry data and/or large series, or in prospective studies to date. With regard to the occurrence of atypical metastases after robotic cystectomy, prospective data are currently lacking and retrospective analysis produce conflicting data. However, general oncological outcome seems not to be affected.Thus, robotic-assisted cystectomy is also from an oncological point of view a good option for patients who have an indication for radical cystectomy.


Identification and molecular phylogeny of Epulorhiza isolates from tropical orchids.
24 isolates of Epulorhiza were obtained from the roots and protocorms of orchids in Singapore. Two groups were distinguished based on morphological and cultural characteristics. Group 1 comprised 20 isolates which were identified as E. repens, while those in group 2 were identified as E. calendulina-like Rhizoctonia. The ITS-5.8S rDNA sequence identity ranged from 88-100% among isolates of E. repens and six sub-groups were further delineated. The sequence identity was 98-100% among E. calendulina-like Rhizoctonia isolates. The sequence identity between E. repens isolates and E. calendulina-like Rhizoctonia isolates ranged from 18-44%. Apparently, isolates from both groups 1 and 2 were genetically distinct. Phylogenetic analysis showed that the distribution of the isolates correlated with the sites and the hosts from which the fungi were isolated. No matching sequences have been found in the GenBank database for the ITS region of E. repens and E. calendulina-like Rhizoctonia.


Insoluble layer deposition and dilatational rheology at a microscale spherical cap interface.
The dilatational properties of insoluble monolayers are important for understanding the mechanics of biological systems and consumer products, but isolating the dilatational response of an interface is challenging due to the difficulties in separating dilatation from shear and other deformation modes. Oscillations of a microscale bubble radius are useful for generating purely dilatational flows, but the current deposition methods for insoluble layers onto fluid interfaces are not easily scaled down. In this paper, we describe a miscible solvent exchange procedure for generating insoluble layers at an air-water interface pinned at the tip of a capillary tens of micrometers in diameter. We show that the amount of surfactant adsorbed at the interface can be controlled by the initial concentration dissolved in isopropanol (the starting solvent) and the volumetric flow rate of solvent exchange. Surface pressure-area isotherms and dilatational moduli are measured concurrently for three insoluble surfactants: palmitic acid (PA), dimyristoylphosphatidylcholine (DMPC) and dipalmitoylphosphatidylcholine (DPPC). The isotherms measured on the microscale interface compare well with previous experiments performed on a Langmuir trough. However, the magnitudes of the dilatational moduli differ from those measured on either Langmuir trough or pendant drop apparatuses. Several possible reasons for the observed differences are discussed. A comparison of the dilatational modulus with the Gibbs elasticity is used to determine the presence of dilatational extra stresses at the interface. The isotherm and dilatational modulus of the insoluble component of the industrial surfactant Tween 80 are measured using this approach. The methods developed here also open the possibility for future study of the important role of finite size effects on microstructure formation and the resulting interfacial mechanics.


Predictors of early abstinence in smokers with schizophrenia.
In patients with schizophrenia, the smoking cessation rate is low and the burden of smoking-related morbidity and mortality is high. Identification of factors associated with abstinence may allow clinicians to optimize treatment prior to a smoking cessation attempt. To identify factors associated with successful smoking cessation in patients with a DSM-IV diagnosis of schizophrenia, we analyzed baseline data from 114 stable outpatient smokers with schizophrenia who participated in 1 of 2 smoking cessation trials. The outcome of interest was 4 weeks' continuous abstinence at the end of a 12-week nicotine dependence treatment intervention. Baseline factors associated with abstinence were identified with univariate methods and entered into a manual, forward-selection multivariable regression model to identify independent predictors of abstinence. The study was conducted from March 1999 to February 2004. Fourteen of 114 participants (12%) had biochemically verified 4 weeks' continuous abstinence at week 12. We included 10 noncorrelated variables with a univariate association with abstinence in a multivariable model, controlling for pharmacotherapy, age, and gender. Age at initiation of smoking and baseline variability in attentiveness, as measured by Continuous Performance Test-AX (CPT-AX) hit reaction time standard error, were independently associated with abstinence. For every year increase in age at initiation of smoking, the OR for abstinence was 1.36 (95% CI = 1.01 to 1.83), p = .048. For every millisecond decrease in the variability of the reaction time of CPT-AX, the OR for achieving abstinence was 1.55 (95% CI = 1.07 to 2.24), p = .021. Later initiation of smoking was associated with increased and baseline attentional impairment with reduced odds of abstinence. Additional research to further our understanding of the relationship between attentional impairment and cigarette smoking in schizophrenia may lead to improved nicotine dependence treatments for this group.


Evidence-based pain management and palliative care in issue four for 2007 of The Cochrane Library.
The Cochrane Library of Systematic Reviews is published quarterly. Issue 4 2007 contains 3298 complete reviews, 1755 protocols for reviews in production and 6761 one-page summaries of systematic reviews published in the general medical literature. In addition, there are citations of 522,000 randomized controlled trials and 10,000 cited papers in the Cochrane methodology register. The health technology assessment database contains 6087 citations. This edition of the Library contains 101 new reviews of which 7 have potential relevance for practitioners in pain and palliative medicine.


Regulation of water flow in the ocular lens: new roles for aquaporins.
The ocular lens is an important determinant of overall vision quality whose refractive and transparent properties change throughout life. The lens operates an internal microcirculation system that generates circulating fluxes of ions, water and nutrients that maintain the transparency and refractive properties of the lens. This flow of water generates a substantial hydrostatic pressure gradient which is regulated by a dual feedback system that uses the mechanosensitive channels TRPV1 and TRPV4 to sense decreases and increases, respectively, in the pressure gradient. This regulation of water flow (pressure) and hence overall lens water content, sets the two key parameters, lens geometry and the gradient of refractive index, which determine the refractive properties of the lens. Here we focus on the roles played by the aquaporin family of water channels in mediating lens water fluxes, with a specific focus on AQP5 as a regulated water channel in the lens. We show that in addition to regulating the activity of ion transporters, which generate local osmotic gradients that drive lens water flow, the TRPV1/4-mediated dual feedback system also modulates the membrane trafficking of AQP5 in the anterior influx pathway and equatorial efflux zone of the lens. Since both lens pressure and AQP5-mediated water permeability ( P H 2 O ${P_{{{\mathrm{H}}_{\mathrm{2}}}{\mathrm{O}}}}$ ) can be altered by changes in the tension applied to the lens surface via modulating ciliary muscle contraction we propose extrinsic modulation of lens water flow as a potential mechanism to alter the refractive properties of the lens to ensure light remains focused on the retina throughout life.


Fitness for work after surgery for lumbar disc herniation: a retrospective study.
This report retrospectively evaluates fitness for work in 3956 cases of surgery for lumbar disc herniation between 1992 and 1994. Patient records were derived from a database including all interventions of the insured population of the largest Belgian sickness fund. The datafile consisted of 126 cases of percutaneous nucleotomy (nucleotomy group), 286 cases of lumbar disc surgery with fusion (fusion group) and 3544 cases of standard lumbar disc surgery (standard group). Fitness to resume work within 12 months after intervention was obtained in about 70% of the patients in the standard and nucleotomy groups but in only 45% of the patients in the fusion group. Ten medicosocial factors were related to fitness for work as outcome measure. Incapacity for work more than 12 months after intervention was defined as a bad outcome. Logistic regression was used to test the combined relative significance of the different variables. For the standard group a long duration of work incapacity before intervention, older age, lower benefit, employment as a blue-collar worker, a long duration of hospital stay and unemployment were significantly associated with a poor outcome. Related factors for the fusion group were a long duration of work incapacity before operation, a long duration of hospital stay and unemployment. For the nucleotomy group, no factor was significantly associated with a poor outcome. For the total group, discectomy combined with fusion was significantly related to a poor outcome whereas a standard discectomy and a percutaneous nucleotomy did not differ in their impact on fitness for work.


Mechanistic insight into size-dependent activity and durability in Pt/CNT catalyzed hydrolytic dehydrogenation of ammonia borane.
We report a size-dependent activity in Pt/CNT catalyzed hydrolytic dehydrogenation of ammonia borane. Kinetic study and model calculations revealed that Pt(111) facet is the dominating catalytically active surface. There is an optimized Pt particle size of ca. 1.8 nm. Meanwhile, the catalyst durability was found to be highly sensitive to the Pt particle size. The smaller Pt particles appear to have lower durability, which could be related to more significant adsorption of B-containing species on Pt surfaces as well as easier changes in Pt particle size and shape. The insights reported here may pave the way for the rational design of highly active and durable Pt catalysts for hydrogen generation.


Assessment of Choroidal Vascularity and Choriocapillaris Blood Perfusion After Accommodation in Myopia, Emmetropia, and Hyperopia Groups Among Children.
To investigate choroidal vascularity (CV) and choriocapillaris blood perfusion before and after accommodation in myopia, emmetropia, and hyperopia groups among children. This study included 39 myopic eyes from 22 subjects, 17 emmetropic eyes from 11 subjects, and 18 hyperopic eyes from 10 subjects. All subjects were children. Choroidal thickness (CT) and CV, including total choroidal area (TCA), luminal area (LA), and stromal area (SA) were measured using swept-source optical coherence tomography (SS-OCT). Choriocapillaris luminal area (CLA) was measured using SS-OCT-angiography before and after accommodation (near reading with an additional -3 diopter lens). For baseline results, except horizontal CV (showing no significant differences between myopia and emmetropia groups), both horizontal and vertical CT and CV were significantly smaller in the myopia group than in the emmetropia or hyperopia groups. In terms of CLA, no significant differences were observed among the myopia, emmetropia, and hyperopia groups. In addition, only myopic eyes showed significant decreases in CT and CV, whereas most CT and CV of emmetropic and hyperopic eyes showed non-significant decreases after accommodation. Furthermore, accommodation induced no significant changes in CLA in the myopia, emmetropia, or hyperopia groups. Myopia had thinner baseline choroid and lower baseline choroidal blood perfusion. Furthermore, myopic eyes were more prone to choroidal thinning and blood perfusion decreases after accommodation.


Diagnostic Images of the Ocular Fundus Using a Low-Cost Portable Endoscope in Premature Patients at Risk of Developing Retinopathy of Prematurity.
The purpose of this article is to describe how fundus images are obtained using a low-cost device: the "Visual Ear Wax Cleaner Tool" portable endoscope (Soonhua Inc., China) connected to a smartphone, after installation of free applications ("Inskam" and "CameraFI") using the smartphone screen as a monitor and after medication mydriasis, local anesthesia, and blepharostat placement. With this endoscope, video recording and fundus imaging are easily performed, for the case of patients at the risk of developing retinopathy of prematurity (ROP), facilitating timely screening in order to start treatment in patients who require it. This fundus imaging technique shares certain similarities with the RetCam® (Clarity, Pleasaton California) system, which performs real-time fundus imaging providing the ability to record and document findings and capture images from the video footage, with high quality and definition, although with a smaller angle of vision. The capture of images using a smartphone allows storing and sharing the images. These are devices which are generally accessible and portable and which use simplified energy sources, requiring very simple training. The low-cost, easy-to-learn technique and quick sharing of images through communication networks make this a tool to be considered for the practice of telemedicine.


Clinical relevance of regulatory T cells monitoring in the peripheral blood of ovarian cancer patients.
Tregs play a suppressive role in the control of antitumour immunity. In this study we evaluated the relevance of prospective monitoring of peripheral blood regulatory T cells (Tregs) as a potential prognostic marker of future outcome of epithelial ovarian cancer in patients with or without a metronomic chemotherapy. 46 patients diagnosed with the ovarian cancer were enrolled in the study and divided into groups according to the stage of the disease, outcome of the surgery and treatment received. Proportions of Tregs in the peripheral blood samples were evaluated using flow cytometry. We show that the early stage of the disease and absence of the tumor residuum after radical surgery are the most important factors predicting a favourable clinical outcome in the ovarian cancer. We did not show any significant effect of consolidation chemotherapy with metronomic doses of etoposide or cyclophosphamide on the peripheral blood Tregs and on the clinical outcome. The slope of the Tregs trend line was a significant predictor of an early relapse, even after controlling for stage and tumor residuum after the surgical debulking by using the Cox proportional hazard model. This study shows that the faster kinetics of Tregs increase in the peripheral blood, expressed as the slope of the Tregs trend line, is a significant predictor of ovarian cancer early relapse hazard. However, due to its relatively low specificity, the informative value of regular monitoring of Tregs kinetics in the peripheral blood for the subsequent clinical outcome is limited.


[Mechanisms of lung oncogenesis].
Precancerous lesions of the bronchial epithelium are dysplasias and in situ carcinomas. Squamous metaplasia has not yet been considered as a true malignant state. Epithelial cells, which are able to proliferate (non terminally differentiated) in bronchial tree and alveoli, are the candidates for malignant proliferation (basal cells, mucus cells, Clara cells and type II pneumonocytes). Their initial growth is probably promoted by deregulated autocrine growth factors (EGF, GRP, IGF1), or their receptors (EGF-R). Under continuous carcinogens exposition these proliferating cells accumulate multiple genetic abnormalities affecting dominant oncogenes such as myc and ras, and recessive tumor suppressor genes such as Rb and p53. Neither the order of intervention of these genetic factors nor their correlation with premalignant states have been demonstrated.


9a: risk factor in bone marrow transplantation?
Graft-versus-host disease is a severe complication which may occur even after bone marrow transplantation between HLA identical siblings. Minor transplantation antigens have been implicated as a causal factor. Therefore the influence of the monocyte/granulocyte antigen 9a on GvHD was studied. No influence on GvHD was observed, but absence of the 9a antigen in the donor was associated with an early death of the recipient.


Transplacental Respiratory Syncytial Virus and Influenza Virus Antibody Transfer in Alaska Native and Seattle Mother-Infant Pairs.
Alaska Native (AN) infants are at risk for severe disease due to respiratory syncytial virus (RSV) and influenza. Maternal immunization protects young infants through transplacental antibody transfer. RSV- and influenza-specific transplacental antibody transfer in mother-infant pairs has not previously been evaluated in the AN population. Serum samples collected during pregnancy and at birth from AN mother-infant pairs in the Yukon-Kuskokwim Delta region (YKD) of Alaska (2000-2011; n = 75) and predominantly white pairs in Seattle, Washington (2014-2016; n = 57), were tested for RSV and influenza antibody using a microneutralization and hemagglutination inhibition assay, respectively, and compared between sites. Mean RSV antibody concentrations in pregnant women in YKD and Seattle were similar (log2 RSV antibody 10.6 vs 10.7, P = .86), but cord blood RSV antibody concentrations were significantly lower in infants born to mothers in YKD compared with Seattle (log2 RSV antibody 11.0 vs 12.2, P < .001). Maternal and cord blood influenza antibody concentrations were lower for women and infants in YKD compared with Seattle for all 4 influenza antigens tested (all P < .05). The mean cord to maternal RSV antibody transfer ratio was 1.15 (standard deviation [SD], 0.13) in mother-infant pairs in Seattle compared with 1.04 (SD, 0.08) in YKD. Mean cord blood to maternal antibody transfer ratios for influenza antigens ranged from 1.22 to 1.42 in Seattle and from 1.05 to 1.59 in YKD. Though the transplacental antibody transfer ratio was high (>1.0) for both groups, transfer ratios for RSV antibody were significantly lower in AN mother-infant pairs. Further studies are needed to elucidate the impact of lower transplacental antibody transfer on infant disease risk in rural Alaska.Alaska Native and continental US mother-infant pairs have high transplacental antibody transfer ratios (>1.0) for influenza and respiratory syncytial virus, but anti-respiratory syncytial virus antibody levels are significantly lower in Alaska Native pairs than in those from the continental US.


Reproducible, rugged, and inexpensive photocathode x-ray diode.
The photoemissive cathode type of x-ray diode (XRD) is popular for measuring time and spectrally resolved output of pulsed power experiments. Vitreous carbon XRDs currently used on the Sandia National Laboratories Z-machine were designed in the early 1980s and use materials and processes no longer available. Additionally cathodes used in the high x-ray flux and dirty vacuum environment of a machine such as Z suffer from response changes requiring recalibration. In searching for a suitable replacement cathode, we discovered very high purity vitreous-carbon planchets are commercially available for use as biological substrates in scanning electron microscope (SEM) work. After simplifying the photocathode mounting to use commercially available components, we constructed a set of 20 XRDs using SEM planchets that were then calibrated at the National Synchrotron Light Source at Brookhaven National Laboratory. We present comparisons of the reproducibility and absolute calibrations between the current vitreous-carbon XRDs and our new design.


The molecular mechanism of non-covalent inhibitor WU-04 targeting SARS-CoV-2 3CLpro and computational evaluation of its effectiveness against mainstream coronaviruses.
There is an urgent need for highly effective therapeutic agents to interrupt the continued spread of SARS-CoV-2. As a pivotal protease in the replication process of coronaviruses, the 3CLpro protein is considered as a potential target of drug development to stop the spread and infection of the virus. In this work, molecular dynamics (MD) simulations were used to elucidate the molecular mechanism of a novel and highly effective non-covalent inhibitor, WU-04, targeting the SARS-CoV-2 3CLpro protein. The difference in dynamic behavior between the apo-3CLpro and the holo-3CLpro systems suggests that the presence of WU-04 inhibits the motion amplitude of the 3CLpro protein relative to the apo-3CLpro system, thus maintaining a stable conformational binding state. The energy calculations and interaction analysis show that the hot-spot residues Q189, M165, M49, E166, and H41 and the warm-spot residues H163 and C145 have a strong binding capacity to WU-04 by forming multiple hydrogen bonds and hydrophobic interactions, which stabilizes the binding of the inhibitor. After that, the resistance of WU-04 to the six SARS-CoV-2 variants (Alpha, Beta, Gamma, Delta, Lambda, and Omicron) and two other mainstream coronavirus (SARS-CoV and MERS-CoV) 3CLpro proteins was further investigated. Excitingly, the slight difference in energy values relative to the SARS-CoV-2 system indicates that WU-04 is still highly effective against the coronaviruses, which becomes crucial evidence that WU-04 is a pan-inhibitor of the 3CLpro protein in various SARS-CoV-2 variants and other mainstream coronaviruses. The study will hopefully provide theoretical insights for the future rational design and improvement of novel non-covalent inhibitors targeting the 3CLpro protein.


The effect of silage and concentrate type on intake behavior, rumen function, and milk production in dairy cows in early and late lactation.
The objective of this experiment was to evaluate the effect of feeding total mixed rations (TMR) that differ in structural and nonstructural carbohydrates to dairy cows in early and late lactation on short-term feed intake, dry matter intake (DMI), rumen fermentation variables, and milk yield. A 5 x 5 Latin square experiment with 15 dairy cows was repeated during early and late lactation. The 5 treatments were a TMR with (all on dry matter basis) 55% roughage (a 50:50 mixture of corn silage and grass silage) and 45% concentrate (a 50:50 mixture of concentrate rich in structural carbohydrates and concentrate rich in nonstructural carbohydrates; treatment CON), a TMR with the concentrate mixture and 55% grass silage (RGS) or 55% corn silage (RCS), and a TMR with the roughage mixture and 45% of the concentrate rich in structural carbohydrates (CSC) or the concentrate rich in nonstructural carbohydrates (CNS). Meal criteria, determined using the Gaussian-Gaussian-Weibull method per animal per treatment, showed an interaction between lactation stage and treatment. Feed intake behavior variables were therefore calculated with meal criteria per treatment-lactation stage combination. Differences in feed intake behavior were more pronounced between treatments differing in roughage composition than between treatments differing in concentrate composition, probably related to larger differences in chemical composition and particle size between corn silage and grass silage than between the 2 concentrates. The number of meals was similar between treatments, but eating time was greater in RGS (227 min/d) and lesser in RCS (177 min/d) than the other treatments. Intake rate increased when the amount of grass silage decreased, whereas meal duration decreased simultaneously. These effects were in line with a decreased DMI of the RGS diet vs. the other treatments, probably related to the high neutral detergent fiber (NDF) content. However, this effect was not found in CSC, although NDF content of the TMR, fractional clearance rate of NDF, and fractional degradation rate of NDF was similar between CSC and RGS. Rumen fluid pH was lesser, and molar proportions of acetic acid and of propionic acid were lesser and greater, respectively, in RCS compared with all other diets. Milk production did not differ between treatments. There was no effect of type of concentrate on milk composition, but diet RCS resulted in a lesser milk fat content and greater milk protein content than diet RGS. Lactation stage did affect short-term feed intake behavior and DMI, although different grass silages were fed during early and late lactation. The results indicate that short-term feed intake behavior is related to DMI and therefore may be a helpful tool in optimizing DMI and milk production in high-production dairy cows.


Immunohistochemical evaluation of ERG expression in various benign and malignant tissues.
The transmembrane protease, serine 2-E twenty-six related gene (TMPRSS2-ERG) fusion leading to ERG overexpression, was detected in approximately 50% of prostate cancers (ranging from 35-70%). However, the published data on ERG expression in tumors from other organs and normal tissues were limited. In this study, we investigated the expression of ERG in TMA sections of various normal tissues (N=452) and carcinomas (N=1,129) from various organs, including 90 cases of low to intermediate-grade (L-MG) prostatic adenocarcinomas and 36 cases of high-grade (HG) prostatic adenocarcinomas, using a single immunostaining system (Dako). Also included were prostatic biopsies of radiation atypia (N=20), atrophy (N=20), and high-grade prostatic intraepithelial lesion (HGPIN) (N=18). ERG expression was detected in 44% (40/90) of L-MG prostatic adenocarcinomas; in 22% (8/36) of HG prostatic adenocarcinomas; and in 22% (4/18) of HGPIN. No ERG expression was detected in non-prostate carcinomas, normal tissues including prostate and seminal vesicles, benign prostatic tissue with radiation atypia, and atrophy. Our data demonstrate that ERG is a highly specific marker, which may have important implications in the interpretation of prostate biopsies with limited cancers. In addition, its high diagnostic specificity may be useful in identifying a prostatic primary when working on a tumor of uncertain origin. Partly presented at the United States and Canadian Academy of Pathology Annual Meeting in March 2011.


Quantification of material loss from the neck piece taper junctions of a bimodular primary hip prosthesis. A retrieval study from 27 failed Rejuvenate bimodular hip arthroplasties.
The early failure and revision of bimodular primary total hip arthroplasty prostheses requires the identification of the risk factors for material loss and wear at the taper junctions through taper wear analysis. Deviations in taper geometries between revised and pristine modular neck tapers were determined using high resolution tactile measurements. A new algorithm was developed and validated to allow the quantitative analysis of material loss, complementing the standard visual inspection currently used. The algorithm was applied to a sample of 27 retrievals (in situ from 2.9 to 38.1 months) of the withdrawn Rejuvenate modular prosthesis. The mean wear volumes on the flat distal neck piece taper was 3.35 mm(3) (0.55 to 7.57), mainly occurring in a characteristic pattern in areas with high mechanical loading. Wear volume tended to increase with time to revision (r² = 0.423, p = 0.001). Implant and patient specific data (offset, stem size, patient's mass, age and body mass index) did not correlate with the amount of material loss observed (p > 0.078). Bilaterally revised implants showed higher amounts of combined total material loss and similar wear patterns on both sides. The consistent wear pattern found in this study has not been reported previously, suggesting that the device design and materials are associated with the failure of this prosthesis.


Evaluation the possibility of vortex-induced resonance for a multistage pressure reducing valve.
A multistage pressure reducing valve is presented in this paper. The pressure reducing components are specially designed to not only control the flow rate but also effectively prevent the cavitation vibration. However, when the fluid flows through the pressure reducing components, the divergence and shedding of the vortices in the flow field seriously affect the stability of the valve and cause vortex-induced vibration. Especially, the main frequency of the vortex shedding is in the same frequency range as the modal frequency of the valve, the vortex-induced resonance of the valve occurs. It seriously affects the safety of a control system. In this paper, by monitoring the lift coefficient of the vortex cross flow in the valve, the frequency spectrum information of the lift coefficient is used as the novelty indexes to indicate vortex-induced vibration of the fluid in the valve. The main frequency and amplitude of vortex-induced vibration are obtained. The factors affecting the vortex-induced vibration of the fluid are analyzed. The results indicate that vortex-induced vibration is the most serious when the valve is opened or closed. The variation of the flow velocity and the pressure difference have obvious effects on vortex-induced vibration of the valve. The intensity of the variation affects the main frequency and amplitude of vortex-induced vibration. Using thermal-fluid-solid coupling modal analysis instead of traditional modal analysis, the modal frequency under the working state of the valve is obtained. It is compared with the main frequency of vortex shedding, and vortex-induced resonance does not occur in the multistage pressure reducing valve.


A cytochemical staining procedure for succinate dehydrogenase activity in pre-ovulatory mouse oocytes embedded in low gelling temperature agarose.
We describe a cytochemical staining procedure for succinate dehydrogenase (SDH) activity in pre-ovulatory mouse oocytes. The oocytes were embedded in low gelling temperature agarose and treated with caffeine before cytochemical staining in the presence of nitro blue tetrazolium (NBT), phenazinemethosulfate (PMS), and succinate. This resulted in intense staining of the oocytes by formazan precipitate. The level of aspecific formazan production in the absence of succinate was very low. We applied the procedure to oocytes matured in vitro and found that the location of the formazan precipitate as a result of SDH activity correlated well with the location of mitochondria. The chromatin of the cytochemically stained oocytes could subsequently be analyzed by means of the DNA-specific fluorochrome DAPI. In pre-ovulatory oocytes, we found a correlation between chromatin organization and the location of mitochondria: in oocytes with an intact germinal vesicle the mitochondria were uniformly distributed in the cytoplasm, as shown by fine grains of formazan precipitate. In oocytes with condensed chromatin the mitochondria apparently had clustered, because the formazan precipitate was more coarse in these cells.


Optimizing Immunosuppressive Regimens Among Living-Donor Renal Transplant Recipients.
We review different immunosuppressant protocols used for living-donor kidney transplant recipients at our center. Many prospective randomized studies from our center have been reported between March 1976 and 2016, with more than 2700 renal transplant procedures conducted. The first study was a prospective randomized trial of azathioprine versus cyclosporine. The second study compared triple therapy (prednisolone + azathioprine + cyclosporine) versus conventional therapy (prednisolone + azathioprine). The third study was a cost-saving study, in which 100 patients received ketoconazole along with the triple regimen. Another trial demonstrated the advantages of a microemulsion form of cyclosporine. A subsequent trial compared calcineurin inhibitor minimization versus avoidance protocols. Rescue therapies were carried out to intensify immunosuppressive regimens after repeated rejection. In addition, steroid-free regimens were evaluated during both short- and long-term treatment. A recent trial reported a step-forward avoidance protocol with a calcineurin inhibitor and a steroid-free regimen, whereas another current study is the TRANSFORM one. The rationale behind antibody therapy was tho roughly evaluated among living-donor renal trans plant recipients with different agents, including basiliximab, daclizumab, antithymocyte globulin, and alemtuzumab. Earlier studies have demonstrated the efficacy of conventional regimens without induction therapy, especially in longer follow-up. The standard triple therapy has emerged with intensified immunosuppressive and lowered dose of each drug, especially cyclosporine. In minimization studies, no significant differences were encountered regarding patient and graft survival, even in the long-term. Steroid avoidance was safe and effective. Calcineurin inhibitors and steroid-free regimens have shown comparable patient and graft survival. Induction therapy has lowered the incidence and severity of acute rejection. A better 5-year graft survival and less posttransplant complications have been achieved with steroid avoidance after induction with basiliximab. Induction therapy did not affect graft and patient survival rates despite lowered incidence and severity of acute rejections.


A hybrid CNN-LSTM model for pre-miRNA classification.
miRNAs (or microRNAs) are small, endogenous, and noncoding RNAs construct of about 22 nucleotides. Cumulative evidence from biological experiments shows that miRNAs play a fundamental and important role in various biological processes. Therefore, the classification of miRNA is a critical problem in computational biology. Due to the short length of mature miRNAs, many researchers are working on precursor miRNAs (pre-miRNAs) with longer sequences and more structural features. Pre-miRNAs can be divided into two groups as mirtrons and canonical miRNAs in terms of biogenesis differences. Compared to mirtrons, canonical miRNAs are more conserved and easier to be identified. Many existing pre-miRNA classification methods rely on manual feature extraction. Moreover, these methods focus on either sequential structure or spatial structure of pre-miRNAs. To overcome the limitations of previous models, we propose a nucleotide-level hybrid deep learning method based on a CNN and LSTM network together. The prediction resulted in 0.943 (%95 CI ± 0.014) accuracy, 0.935 (%95 CI ± 0.016) sensitivity, 0.948 (%95 CI ± 0.029) specificity, 0.925 (%95 CI ± 0.016) F1 Score and 0.880 (%95 CI ± 0.028) Matthews Correlation Coefficient. When compared to the closest results, our proposed method revealed the best results for Acc., F1 Score, MCC. These were 2.51%, 1.00%, and 2.43% higher than the closest ones, respectively. The mean of sensitivity ranked first like Linear Discriminant Analysis. The results indicate that the hybrid CNN and LSTM networks can be employed to achieve better performance for pre-miRNA classification. In future work, we study on investigation of new classification models that deliver better performance in terms of all the evaluation criteria.


A deficient TLR2 signaling promotes airway mucin production in Mycoplasma pneumoniae-infected allergic mice.
The original hygiene hypothesis suggests that early childhood respiratory infections preceding allergen exposure may decrease the prevalence of allergic diseases. We have recently demonstrated that Mycoplasma pneumoniae infection preceding allergen exposure reduced allergic responses in mice. However, the molecular mechanisms underlying the protective role of M. pneumoniae in allergic responses, particularly airway mucin production, remain unclear. Wild-type and Toll-like receptor 2 (TLR2)-deficient mice with a respiratory M. pneumoniae infection preceding allergen (ovalbumin) challenge were utilized to determine the regulatory role of TLR2-IFN-gamma signaling pathway in airway mucin expression. Furthermore, air-liquid interface cultures of mouse primary tracheal epithelial cells were performed to examine the effects of IFN-gamma on mucin expression. In wild-type mice, M. pneumoniae infection preceding allergen challenge significantly reduced airway mucins but increased IFN-gamma. In sharp contrast, in TLR2-deficient mice, M. pneumoniae preceding allergen challenge resulted in increased mucin protein without a noticeable change of IFN-gamma. In cultured mouse primary tracheal epithelial cells, IFN-gamma was shown to directly inhibit mucin expression in a dose-dependent manner. Our study demonstrates for the first time that a respiratory M. pneumoniae infection preceding allergen challenge reduces airway epithelial mucin expression in part through TLR2-IFN-gamma signaling pathway. A bacterial infection in asthmatic subjects with weakened TLR2-IFN-gamma signaling may result in an exaggerated airway mucin production.


Urinary incontinence in elite female athletes and dancers.
The aim of this study was, to determine the frequency of urinary loss in elite women athletes and dancers. Elite athletes in eight different sports, including ballet, filled in an evaluated questionnaire about urinary incontinence while participating in their sport/dancing and during daily life activities. A total of 291 women with a mean age of 22.8 years completed the questionnaire, providing a response rate of 73.9%. Overall, 151 women (51.9%) had experienced urine loss, 125 (43%) while participating in their sport and 123 (42%) during daily life. The proportion of urinary leakage in the different sports was: gymnastics 56%, ballet 43%, aerobics 40%, badminton 31%, volleyball 30%, athletics 25%, handball 21% and basketball 17%. During sport 44% had experienced leakage a few times, 46.4% now and then, and 9.6% frequently. During daily life the figures were: 61.7% a few times, 37.4% now and then, and 0.8% frequently. Of those who leaked during sport, 95.2% experienced urine loss while training versus only 51.2% during competition (P<0.001). The activity most likely to provoke leakage was jumping. Sixty per cent (91/151) occasionally wore pads or panty shields because of urine loss. Urinary leakage is common among elite athletes and dancers, particularly during training, but also during daily life activities.


Effects of manual versus voice-activated dialing during simulated driving.
We measured driving performance (lane-keeping errors, driving times, and glances away from the road scene) in a video driving simulator for 24 volunteers who each drove alone on a 10.6-km multicurved course while simultaneously placing calls on a mobile phone subscribed to a voice-activated dialing system. Driving performance also was measured for the same distance while participants manually dialed phone numbers and while they drove without dialing. There were 22% fewer lane-keeping errors (p<.01) and 56% fewer glances away from the road scene (p<.01) when they used voice-activated dialing as compared to manual dialing. Significantly longer driving times in both of the dialing conditions as compared to the No Dialing condition are discussed in terms of the hypothesis that drivers decrease driving speed to compensate for the demands of the secondary phone tasks.


Specific detection of quinoproteins by redox-cycling staining.
Quinones and related quinonoid substances catalyze redox cycling at an alkaline pH in the presence of excess glycine as reductant. With nitroblue tetrazolium and oxygen present there is concomitant reduction of the tetrazolium to formazan. This property of quinonoid compounds is used for the specific staining of quinoproteins, separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and electroblotted onto nitrocellulose. The dopa-containing vitelline proteins and the 6-hydroxydopa-containing bovine serum amine oxidase are stained with the nitroblue tetrazolium/glycinate reagent. Also, the mammalian quinoproteins, diamine oxidase and lysyl oxidase, purported to contain pyrroloquinoline quinone, tested positive in this procedure. No quinonoid components were detected in three putative pyrroloquinoline quinone-containing quinoproteins, dopamine beta-hydroxylase, lipoxygenase, and peptidylglycine-amidating monoxygenase. Redox-cycling staining therefore confirms the presence of covalently bound quinones in the copper-dependent amine oxidases, but not in two putative quinoprotein oxygenases. Clarification of the biological significance of quinolation should be facilitated by identification of quinoproteins using this approach.


Significance of tumor-cell receptors in human cancer.
Every tumor cell is equipped with an array of biologically active surface molecules, and several of these function as receptors for various ligands. They include MHC, or in the case of humans, HLA antigens, cytokine receptors, cell-adhesion molecules, growth factor receptors, Fas/Fas-ligand molecules and others. Their expressions are a subject to alterations, usually to the advantage of tumor growth and spread. Some appear on tumor cells de novo, having no counterparts on the respective normal cells. Detailed knowledge about the expression of tumor-cell receptors and their genotypes, in particular of cancerous ones, may provide information essential for the creation of tools for specific tumor immunotherapy.


Draft Genome Sequence of Taylorella equigenitalis Strain MCE529, Isolated from a Belgian Warmblood Horse.
Taylorella equigenitalis is the causative agent of contagious equine metritis (CEM), a sexually transmitted infection of horses. We herein report the genome sequence of T. equigenitalis strain MCE529, isolated in 2009 from the urethral fossa of a 15-year-old Belgian Warmblood horse in France.


Platelet-rich plasma may not provide any additional effect when associated with guided bone regeneration around dental implants in dogs.
The aim of this study was to evaluate histometrically bone healing in surgically created dehiscence-type defects around titanium implants treated with an association of platelet-rich plasma (PRP) and guided bone regeneration (GBR). Ten male adult mongrel dogs were used, from which the three low premolars (P2, P3, P4) and the first molar were extracted. Three months after teeth extraction, two implant sites were bilaterally drilled, buccal bone dehiscences were created and four titanium implants were placed. Dehiscences were randomly assigned to the following groups: (1) PRP, (2) GBR, (3) PRP+GBR and (4) control. After 3 months, the animals were sacrificed and the implants and adjacent hard tissues were processed for undecalcified sections. Bone-to-implant contact (BIC), bone density within the limits of implant threads (BW), bone density (BD) and new bone area (BA) in a zone lateral to the implant corresponding to bone defects were obtained and measured. Intergroup analysis (two-way ANOVA -alpha=5%) demonstrated that when PRP was utilized,no differences were observed for all parameters (P>0.05). However, significant differences were observed for BIC and BW toward membrane-treated groups (P<0.05). Within the limits of this study, it was concluded that PRP does not exert additional effects on bone healing in bone defects created around dental implants and treated by GBR.


Epstein-Barr virus latent membrane protein 2A preferentially signals through the Src family kinase Lyn.
Latent membrane protein 2A (LMP2A) is a viral protein expressed during Epstein-Barr virus (EBV) latency in EBV-infected B cells both in cell culture and in vivo. LMP2A has important roles in modulating B-cell receptor signal transduction and provides survival and developmental signals to B cells in vivo. Although Lyn has been shown to be important in mediating LMP2A signaling, it is still unclear if Lyn is used preferentially or if LMP2A associates promiscuously with other Src family kinase (SFK) members. To investigate the role of various SFKs in LMP2A signaling, we crossed LMP2A transgenic mice (TgE) with Lyn(-/-), Fyn(-/-), or Blk(-/-) mice. TgE Lyn(-/-) mice had a larger immunoglobulin M (IgM)-positive B-cell population than TgE mice, suggesting that the absence of Lyn prevents LMP2A from delivering survival and developmental signals to the B cells. Both TgE Fyn(-/-) and TgE Blk(-/-) mice have an IgM-negative population of splenic B cells, similar to the TgE mice. LMP2A was also transiently transfected into the human EBV-negative B-cell line BJAB to determine which SFK members associate with LMP2A. Lyn was detected in LMP2A immunoprecipitates, whereas Fyn was not. Both Lyn and Fyn were able to bind to an LMP2A mutant which contained a sequence shown previously to bind tightly to the SH2 domain of multiple SFK members. From these results, we conclude that LMP2A preferentially associates with and signals through Lyn compared to its association with other SFKs. This preferential association is due in part to the SH2 domain of Lyn associating with LMP2A.


The expression of selected genes linked to metabolic homeostasis in obese pansteatitis-suffering Mozambique tilapia, Oreochromis mossambicus (Peters).
The Oreochromis mossambicus (Peters) population inhabiting Lake Loskop, South Africa, is characterized by a high incidence of obesity and pansteatitis. We investigated potential links between the impaired health of Lake Loskop O. mossambicus and the endocrine system by assessing the expression of selected genes associated with the thyroid and adrenal endocrine axes as well as peroxisome proliferator-activated receptor gamma (pparg). Moreover, contaminant-induced thyroid and/or metabolic modulation in Lake Loskop water was evaluated using juvenile O. mossambicus in laboratory exposures. The expression of thyroid hormone receptor alpha (thra) and type 2 deiodinase (dio2) was higher in Lake Loskop O. mossambicus than fish from another population, suggesting a degree of thyroid disruption. The altered gene expression may be a consequence, rather than cause of obesity. Expression of dio2 and pparg was higher in juvenile O. mossambicus exposed to unfiltered compared to filtered lake water, and our data suggest fasting as causative factor. Micro-organism abundance can therefore be a confounding factor in studies applying molecular markers to test for thyroid modulation by environmental waters. Pansteatitis was not a significant source of variance in the expression of any of the genes investigated, suggesting that the disease is not associated with disrupted endocrine signalling.


Perspective and conception of Thai gynecologic oncologists in palliative care.
Palliative care evidently increases the quality of life among the patients with advanced cancer. However, there are very few studies on the aspects of the physicians' ideas, conceptions, or the effects of their ideas in palliative care quality, especially in Asian countries. This study aimed to evaluate the conception and perspective on palliative care in Thai gynecologic oncologists. The online survey was distributed to all certificated Thai gynecologic oncologists. The survey could be accessed via working email address, hyperlink, or QR code during May 2020 and January 2021. A 5-point Likert scale captured the perspectives and concepts of palliative care. The association between respondents' characteristics and their choices of content in palliative care, together with their decision making in specified clinical scenarios was analyzed. A total of 207 completed surveys from 320 Thai gynecologic oncologists were received (64.69% participation rate). They prospected a willingness to give the advices to both patients and their families (85.50%), and strongly agreed to introduce palliative care in any stage of cancer at the time of diagnosis (75.80%). The numbers of their palliative cases per year were 5-20 (57.97%) and the palliative care teams were available in their hospitals. They decided to offer early palliative care and do-not-resuscitate, especially for the elders, or patients with advance stages, or recurrent disease. We found that gynecologic oncologists who previously experienced a palliative care training did not show any difference in decision making in specified clinical scenarios, compared with who did not. Thai gynecologic oncologists responded to the conceptions and perspectives in palliative care. Their concepts of early and willingness to offer a palliative care especially in the elders, advanced stage, or recurrent patients were proven, regardless of the experience in palliative care training.


Distribution on Warp Maps for Alignment of Open and Closed Curves.
Alignment of curve data is an integral part of their statistical analysis, and can be achieved using modelor optimization-based approaches. The parameter space is usually the set of monotone, continuous warp maps of a domain. Infinite-dimensional nature of the parameter space encourages sampling based approaches, which require a distribution on the set of warp maps. Moreover, the distribution should also enable sampling in the presence of important landmark information on the curves which constrain the warp maps. For alignment of closed and open curves in ℝ d , d = 1, 2, 3, possibly with landmark information, we provide a constructive, point-process based definition of a distribution on the set of warp maps of [0, 1] and the unit circle S , that is, (1) simple to sample from, and (2) possesses the desiderata for decomposition of the alignment problem with landmark constraints into multiple unconstrained ones. For warp maps on [0, 1], the distribution is related to the Dirichlet process. We demonstrate its utility by using it as a prior distribution on warp maps in a Bayesian model for alignment of two univariate curves, and as a proposal distribution in a stochastic algorithm that optimizes a suitable alignment functional for higher-dimensional curves. Several examples from simulated and real datasets are provided.


MSCNE:Predict miRNA-Disease Associations Using Neural Network Based on Multi-Source Biological Information.
The important role of microRNA (miRNA) in human diseases has been confirmed by some studies. However, only using biological experiments has greater blindness, leading to higher experimental costs. In this paper a high-efficiency algorithm based on a variety of biological source information and applying a combination of a convolutional neural network (CNN) feature extractor and an extreme learning machine (ELM) classifier is proposed. Specifically, the semantic similarity of diseases, the gaussian interaction profile kernel similarity of the four biological information of miRNA, disease, long non-coding RNA (lncRNA) and environmental factors (EFs), and the similarities of miRNAs are fused together. Among them, miRNAs similarity is composed of miRNA target information, sequence information, family information, and function information. Then, the dimensionality of the data set is reduced by the autoencoder (AE). Finally, deep features are extracted through CNN, and then the association between miRNA and disease is predicted by ELM. The experimental results show that the average AUC value based on the multi-biological source information (MSCNE) model is 0.9630, which can reach higher performance than the other classic classifier, feature extractor mentioned and the other existing algorithms. The results show the MSCNE algorithm is effective to predict the correlation of miRNA-disease.


The relationship between quantitative perfusion and functional results and acquisition time with reduced administered activity for 99mTc tetrofosmin myocardial gated-SPECT.
The aim of this study was to assess the relationship between administered 99mTc tetrofosmin activity in myocardial gated-SPECT and findings of myocardial perfusion and left ventricular ejection fraction (LVEF) as markers of diagnostic outcome. Fifty-two patients with heterogeneous cardiac diseases and a clinical referral for myocardial perfusion imaging were prospectively studied. A separate-day acquisition protocol was adopted with a low fixed activity of 370 MBq, which corresponds to an average reduction of 31% with respect to the median value of 533 MBq usually administered in our laboratory. A standard acquisition with a time/frame of 25 seconds was performed (ST). Immediately after the conclusion of the first acquisition, a second acquisition was performed with a high time/frame of 33 seconds (HT), which corresponds to an increase of 31% with respect to standard time/frame adopted in our laboratory. The order of ST and HT acquisitions was randomized in individual patients. The summed stress scores (SSS), the summed rest scores (SRS), the LVEF, and the end-diastolic volume (EDV) were automatically calculated. The image quality score was significantly higher in HT than in ST. No significant differences were found in SSS, SRS, LVEF, and EDV between HT and ST SPECT. The agreement between HT and ST was 84% (kw=0.88) in the correct classification of stress images. The agreement between HT and ST was 84% (k=0.70) in the detection of ischemia and scar. The limits of agreement between the HT and the ST methods were roughly within ±3 points for SSS and SRS, ±13% for poststress LVEF, and ±18 mL for poststress EDV. Using about half of the activity recommended by the current diagnostic reference levels for separate-day myocardial perfusion imaging, the present study demonstrates that images may be obtained using ST protocol with quantitative results comparable with those from studies performed using the HT protocol, which is equivalent to an administered activity of 530 MBq. The former protocol would allow for a significant reduction of the dose to the patients as well as to the operators. Further studies are needed to confirm that this dose-sparing approach does not hamper sensitivity and specificity for coronary stenoses.


Arabidopsis isochorismate synthase functional in pathogen-induced salicylate biosynthesis exhibits properties consistent with a role in diverse stress responses.
Salicylic acid (SA) is a phytohormone best known for its role in plant defense. It is synthesized in response to diverse pathogens and responsible for the large scale transcriptional induction of defense-related genes and the establishment of systemic acquired resistance. Surprisingly, given its importance in plant defense, an understanding of the underlying enzymology is lacking. In Arabidopsis thaliana, the pathogen-induced accumulation of SA requires isochorismate synthase (AtICS1). Here, we show that AtICS1 is a plastid-localized, stromal protein using chloroplast import assays and immunolocalization. AtICS1 acts as a monofunctional isochorismate synthase (ICS), catalyzing the conversion of chorismate to isochorismate (IC) in a reaction that operates near equilibrium (K(eq) = 0.89). It does not convert chorismate directly to SA (via an IC intermediate) as does Yersinia enterocolitica Irp9. Using an irreversible coupled spectrophotometric assay, we found that AtICS1 exhibits an apparent K(m) of 41.5 mum and k(cat) = 38.7 min(-1) for chorismate. This affinity for chorismate would allow it to successfully compete with other pathogen-induced, chorismate-utilizing enzymes. Furthermore, the biochemical properties of AtICS1 indicate its activity is not regulated by light-dependent changes in stromal pH, Mg(2+), or redox and that it is remarkably active at 4 degrees C consistent with a role for SA in cold-tolerant growth. Finally, our analyses support plastidic synthesis of stress-induced SA with the requirement for one or more additional enzymes responsible for the conversion of IC to SA, because non-enzymatic conversion of IC to SA under physiological conditions was negligible.


A novel Brn3-like POU transcription factor expressed in subsets of rat sensory and spinal cord neurons.
Brn3a and Brn3b are mammalian members of the POU class of transcription factors. They are closely related to each other and to Unc86, which determines the normal development of certain cells, including mechanoreceptive sensory neurons in Caenorhabditis elegans. We screened a rat dorsal root ganglion (DRG) cDNA library at moderate stringency with a Brn3a POU-domain probe and identified a novel transcript encoding a POU protein that we have named Brn3c. Brn3c closely resembles Brn3a and Brn3b in its POU-domain and thus helps define a family of Unc86-related mammalian POU factors. Both Brn3a and Brn3c are expressed only in the central and peripheral nervous systems. In the neonatal rat, northern blots revealed a 3.6 kb Brn3a transcript in DRG, spinal cord and hindbrain, and a 2.6 kb Brn3c transcript in DRG and spinal cord. In situ hybridization showed that most DRG neurons express Brn3a whereas only a small subset of neurons expresses Brn3c. In the spinal cord, Brn3a is expressed by many dorsal horn neurons. In contrast, Brn3c is expressed by a very small number of cells in laminae 4/5 of the dorsal horn. These data suggest that Brn3-related POU factors may be involved in the development or function of particular subclasses of sensory and spinal cord neurons.


Low-grade mucoepidermoid carcinoma of salivary glands: characteristic immunohistochemical profile and evidence of striated duct differentiation.
The purpose of the present study is to determine the presence and distribution of epithelial and myoepithelial cells in mucoepidermoid carcinoma (MEC) of salivary glands and to compare them with normal salivary gland tissue and other primary carcinomas. This is in order to establish novel diagnostic criteria and to better understand MEC histogenesis. Formalin-fixed paraffin-embedded tissues from ten well-differentiated MECs, three adenoid cystic carcinomas (ACC), four acinic cell carcinomas (AC), and three epithelial-myoepithelial carcinomas (EMCC) of salivary glands were studied with immunohistochemistry using antibodies that recognise antigens indicative of epithelial and myoepithelial cell differentiation. An anti-mitochondrial antibody was also employed. Normal salivary tissue was present for comparative study in non-tumorous areas of the same section from 12 cases. MEC contained numerous keratin-positive cells. Anti mitochondrial antibody was diffusely positive in all ten of these tumours. Smooth muscle actin, h-caldesmon, and smooth muscle heavy chain myosin, which are indicative of myoepithelial cell differentiation, were negative. Rare cells in only one case were stained by calponin. Cytokeratin 14 (CK14) and anti mitochondrial antibody stained cells located mainly at the periphery of neoplastic nests and cystic spaces, while CK7 was mainly present in cells bordering gland lumina (zoning pattern). The immunohistochemical cell profile was similar to that seen in striated normal ducts. All others tumours studied showed a different immunohistochemical pattern, mostly consisting of a lack of mitochondrion-rich cells and the presence of myoepithelial cells in ACC and EMCC. Immunoreactivity in MEC for CK7, CK14 and mitochondrial antibodies appears as a peculiar pattern of staining, different from that of other salivary gland tumors; this seems helpful for diagnostic purposes. In addition, a differentiation of the "striated duct phenotype" is suggested.


Periodic Breathing and Behavioral Awakenings at High Altitude.
Objectives. To study the relationship between nocturnal periodic breathing episodes and behavioral awakenings at high altitude. Methods. Observational study. It is 6-day ascent of 4 healthy subjects from Besisahar (760 meters) to Manang (3540 meters) in Nepal in March 2012. A recording pulse oximeter was worn by each subject to measure their oxygen saturation and the presence of periodic breathing continuously through the night. An actigraph was simultaneously worn in order to determine nocturnal behavioral awakenings. There were no interventions. Results. 187-hour sleep at high altitude was analyzed, and of this, 145 hours (78%) had at least one PB event. At high altitude, 10.5% (95% CI 6.5-14.6%) of total sleep time was spent in PB while 15 out of 50 awakenings (30%, 95% CI: 18-45%) occurring at high altitudes were associated with PB (P < 0.001). Conclusions. Our data reveals a higher than expected number of behavioral awakenings associated with PB compared to what would be expected by chance. This suggests that PB likely plays a role in behavioral awakenings at high altitude.


Concentration dependent diffusion of self-propelled rods.
We examine the persistent random motion of self-propelled rods (SPR) as a function of the area fraction phi and study the effect of steric interactions on their diffusion properties. SPR of length l and width w are fabricated with a spherocylindrical head attached to a beaded chain tail, and show directed motion on a vibrated substrate. The mean square displacement (MSD) on the substrate grows linearly with time t for phi<w/l, before displaying caging as phi is increased, and stops well below the close packing limit. Direction autocorrelations decay progressively slower with phi. We describe the observed decrease of SPR propagation speed c(phi) with a tube model. Further, MSD parallel to the SPR collapse with tau=l/c(phi) and scales as (lt/tau);{2}, and MSD in the perpendicular direction grows progressively slower than l{2}t/tau with phi, consistent with dynamics inside a thinning tube.


Is low-dose methotrexate nephrotoxic? Case report and review of the literature.
Methotrexate (MTX) has become the most commonly prescribed disease-modifying anti-rheumatic drug. However, toxicity is an important drawback of MTX therapy and permanent discontinuation of MTX for adverse effects occurs in 1 patient out of 10. Although high-dose MTX is known to be nephrotoxic, data on low-dose MTX renal effects are scanty. We report an insidious and progressive deterioration of renal function during long-term low-dose MTX in a 59-year-old woman. Kidney biopsy revealed advanced kidney fibrosis with extensive interstitial and glomerular fibrosis, and vascular sclerosis. We suggest that patients on low-dose MTX therapy even alone, should be periodically monitored for creatinine levels.


RUNX2 controls human IPO8 basal transcription in Saos-2 cells.
Runt-related transcription factor 2 (RUNX2) is a vital regulatory factor that controls osteoblast-specific gene expression; however, RUNX2‑regulated genes in human mesenchymal stem cells (hMSCs) remain to be fully elucidated. In the present study, chromatin immunoprecipitation (ChIP)-on-chip analysis of RUNX2 in hMSCs demonstrated that importin 8 (IPO8) may be a novel target gene. The 5' flanking region of the IPO8 gene, which is ~3,300 bp in length, was cloned and inserted into the pGL3‑basic luciferase reporter vector. The results of dual luciferase reporter assays indicated that this segment possessed strong basal promoter activity. Furthermore, the RUNX2 binding site, which encompasses positions ‑496 to ‑501 bp, was required to achieve maximal IPO8 promoter activity in Saos‑2 human osteosarcoma cells. In addition, ChIP analysis indicated that RUNX2 uniquely binds to this specific IPO8 sequence motif. Cells with a knockdown in RUNX2 expression exhibited downregulated IPO8 transcription. Finally, synchronization of IPO8 and RUNX2 expression was observed in Saos‑2 cells cultured in osteoblast‑induction medium. Taken together, these results indicated that RUNX2 regulates IPO8 gene transcription, and may have a contributory role in osteoblast differentiation.


Impaired cardiovascular autonomic control in newly and long-term-treated patients with Parkinson's disease: involvement of L-dopa therapy.
In idiopathic Parkinson's disease (PD), autonomic dysfunction is frequent, causing orthostatic hypotension. The respective roles of disease progression and dopaminergic treatment remain unclear. In this study, we investigated the autonomic control of cardiovascular functions and its relation to L-dopa therapy in both newly diagnosed (ND) and long-term-treated (LT) patients. Study subjects were: (1) nine ND patients never having undergone treatment with L-dopa; (2) 18 LT patients who had been receiving L-dopa treatment for a long period. ND patients were investigated before L-dopa treatment and after stabilization of their L-dopa dosage. LT patients were investigated once with their regular treatment and once after a 12-h interruption of L-dopa treatment; (3) nine healthy subjects served as controls. At each test session, blood pressure (BP), heart rate (HR), plasma catecholamines, heart rate variability (HRV), and spontaneous baroreflex sensitivity were assessed in the supine and upright positions. Before receiving L-dopa medication, ND patients had reduced E/I ratios (HR response/deep breathing) and lowered HRV when compared to controls; this was evidence of early effects of the disease on autonomic HR control. Introduction of L-dopa treatment reduced BP, HR, and plasma levels of adrenaline and noradrenaline. Similar changes were found in LT patients when contrasting the short-term treatment interruption and the usual L-dopa dosage. The treatment-linked increase in plasma dopamine also correlated with the decrease in noradrenaline. These results showed that mild impairment of autonomic cardiovascular control occurred early in the course of PD. They also provided evidence that the side effects of L-dopa aggravated the impairment of the autonomic control of BP and HR.