Protein tyrosine phosphatase-mu differentially regulates neurite outgrowth of nasal and temporal neurons in the retina.
Cell adhesion molecules play an important role in the development of the visual system. The receptor-type protein tyrosine phosphatase, PTPmu is a cell adhesion molecule that mediates cell aggregation and may signal in response to adhesion. PTPmu is expressed in the chick retina during development and promotes neurite outgrowth from retinal ganglion cell (RGC) axons in vitro (Burden-Gulley and Brady-Kalnay, 1999). The axons of RGC neurons form the optic nerve, which is the sole output from the retina to the optic tectum in the chick. In this study, we observed that PTPmu expression in RGC axons occurs as a step gradient, with temporal axons expressing the highest level of PTPmu. PTPmu expression in the optic tectum occurred as a smooth descending gradient from anterior to posterior regions during development. Because temporal RGC axons innervate anterior tectal regions, PTPmu may regulate the formation of topographic projections to the tectum. In agreement with this hypothesis, a differential response of RGC neurites to a PTPmu substrate was also observed: RGCs of temporal retina were unable to extend neurites on PTPmu compared with neurites of nasal retina. When given a choice between PTPmu and a second substrate, the growth cones of temporal neurites clustered at the PTPmu border and stalled, thus avoiding additional growth on the PTPmu substrate. In contrast, PTPmu was permissive for growth of nasal neurites. Finally, application of soluble PTPmu to retinal cultures resulted in the collapse of temporal but not nasal growth cones. Therefore, PTPmu may specifically signal to temporal RGC axons to cease their forward growth after reaching the anterior tectum, thus allowing for subsequent innervation of deeper tectal layers.


A Wnt/Calcium Signaling Cascade Regulates Neuronal Excitability and Trafficking of NMDARs.
Wnt signaling controls multiple biological process, particularly the embryonic development of metazoans. Sustained expression of Wnt signaling components in the mature mammalian CNS and their apparent deregulation in certain neuropathologies suggest that it also plays a part beyond embryonic development to regulate normal brain function. We describe a noncanonical Wnt/Ca2+ signaling cascade that regulates the electrophysiological intrinsic properties of rat neurons, resulting in sustained membrane depolarization and the mobilization of Ca2+ from internal stores. These effects require tyrosine kinase-like orphan receptor 2 (RoR2), activation of PLC, and voltage-gated Ca2+ channels. Activation of this signaling cascade then promotes surface expression of N-methyl-D-aspartate receptors (NMDARs) through a SNARE-dependent mechanism. This neuronal Wnt/Ca2+ signaling pathway represents a mechanism for Wnt ligands to regulate normal brain processes in the mature animal and provides a framework for understanding how alterations in this pathway may contribute to the etiology of psychiatric disorders where NMDARs are compromised.


Fibrous histiocytoma: a histological and statistical analysis of 155 cases.
Various salient histological features were rated from + to +++ in a semiquantitative evaluation of a series of 155 cases of fibrous histiocytoma. Relations between individual histological features, as well as between histological findings, localisation and size of lesions, and age or sex of the patient were tested statistically. Most impressive was an inverse proportional relationship between cellular and fibrillar densities: highly cellular fibrous histiocytomas chiefly showed little fiber formation. Accordingly, cases with marked fiber formation were distinguished by low cellularity. Based on this statistically significant relation, 3 subtypes could be classified on a scale of increasing fiber formation and decreasing cellular density. The majority of cases showed medium cellularity and fibrillar density, with distinct storiform (spokewheel or "whirlygig") pattern which is compatible with typical storiform histocytoma, including clincally progressive, recurrant FH and/or "dermatofibrosarcoma protuberans". The typical patient was more frequently female than male, 40 years of age with a 0.5 to 1.0 cm size tumor node in the lower extremities located in the corium, often with beginning infiltration of the subcutaneous fat tissue.


Effect of intake manifold geometry on cylinder-to-cylinder variation and tumble enhancement in gasoline direct injection engine.
In this study, the effect of intake manifold geometry on cylinder-to-cylinder variation was investigated considering the volumetric efficiency, early tumble development, turbulent kinetic energy, and spark plug gap velocity using computational fluid dynamic program, CONVERGE v2.4. The simulation model was validated based on the PIV experiment in the cylinder and Mie-scattering experiment of intake manifold, and its results agreed well with the experiment results. The curved intake manifold and straight manifold were compared. As a result, it was advantageous for cylinder-to-cylinder variation in the straight intake manifold compared to the curved intake manifold in perspective of volumetric efficiency which were a maximum deviation of 1.7% in curved manifold and 0.6% in straight manifold. And the straight manifold had an effect of the strengthening the in-cylinder flow, so that the turbulent kinetic energy near TDC was increased to maximum 11% than curved manifold. And considering the effect of manifold curve radius on in-cylinder flow intensity in straight manifold, with increasing engine speed, the in-cylinder flow intensified during compression with decreasing the intake manifold radius due to the short distance between manifold inlet and port. Especially at 2000 rpm, the tumble ratio increased 55% at intake manifold radius of 10 cm than of 7 cm at bTDC 280 deg. Therefore, for the purpose of enhancing the in-cylinder flow near spark plug timing, shortened distance between intake manifold inlet and port and increasing the manifold radius is required.


Crab: snail size-structured interactions and salt marsh predation gradients.
We studied size-structured predator-prey interactions between blue crabs (Callinectes sapidus) and marsh periwinkles (Littoraria irrorata) with a combination of field studies, laboratory experiments and individual-based modeling. Size distributions of Littoraria differed among years at the same sites in a salt marsh and could largely be explained by dominance of strong cohorts in the population. At a given site, abundance increased with elevation above tidal datum. Size-selective predation by blue crabs does not appear to be an important regulator of snail size distributions but may have a major effect on local abundance. Laboratory studies indicated that predator-prey interactions between Callinectes and Littoraria are strongly size-dependent. Crabs were generally effective at feeding on periwinkles at size ratios greater than approximately 6 (crab width: snail length). At lower size ratios crabs were far less effective at manipulating the snails, which often survived but with damaged shells. An individual-based model which incorporated information about incidence of snail shell scarring (resulting from non-lethal interactions) and snail density, predicted reduced predation rates and smaller average crab size with distance from the low tide refugium for crabs.


Electrophysiological predictors of cognitive-behavioral therapy outcome in tic disorders.
Cognitive-behavioral therapy (CBT) constitutes an empirically based treatment for tic disorders (TD), but much remains to be learned about its impact at the neural level. Therefore, we examined the electrophysiological correlates of CBT in TD patients, and we evaluated the utility of event-related potentials (ERP) as predictors of CBT outcome. ERPs were recorded during a stimulus-response compatibility (SRC) task in 26 TD patients and 26 healthy controls. Recordings were performed twice, before and after CBT in TD patients, and with a similar time interval in healthy controls. The stimulus- and response-locked lateralized readiness potentials (sLRP & rLRP) were assessed, as well as the N200 and the P300. The results revealed that before CBT, TD patients showed a delayed sLRP onset and larger amplitude of both the sLRP and rLRP peaks, in comparison with healthy controls. The CBT induced an acceleration of the sLRP onset and a reduction of the rLRP peak amplitude. Compared to healthy controls, TD patients showed a more frontal distribution of the No-Go P300, which was however not affected by CBT. Finally, a multiple linear regression analysis including the N200 and the incompatible sLRP onset corroborated a predictive model of therapeutic outcome, which explained 43% of the variance in tic reduction following CBT. The current study provided evidence that CBT can selectively normalize motor processes relative to stimulus-response compatibility in TD patients. Also, ERPs can predict the amount of tic symptoms improvement induced by the CBT and might therefore improve treatment modality allocation among TD patients.


Smartphone-Based Psychotherapeutic Interventions in Blended Care of Cancer Survivors: Nested Randomized Clinical Trial.
Cancer is related to not only physical but also mental suffering. Notably, body image disturbances are highly relevant to cancer-related changes often persisting beyond recovery from cancer. Scalable and low-barrier interventions that can be blended with face-to-face psychotherapy for cancer survivors are highly warranted. The aim of the study is to investigate whether smartphone-based bodily interventions are more effective to improve the mood of patients with cancer than smartphone-based fairy tale interventions (control intervention). We recruited patients with cancer in 2 Swiss hospitals and conducted daily, fully automated smartphone-based interventions 6 times a week for 5 consecutive weeks, blended with weekly face-to-face group body psychotherapy. We applied 2 types of smartphone-based interventions using a within-subject design, randomly assigning patients daily to either bodily interventions or fairy tales. Each intervention type was presented 3 times a week. For this secondary analysis, 3-level mixed models were estimated with mood assessed by the 3 Multidimensional Mood Questionnaire subscales for good-bad mood, wakefulness, and calmness as key indicators. In addition, the effects on experience of presence, vitality, and burden assessed with visual analog scales were investigated. Based on the data from s=732 interventions performed by 36 participants, good-bad mood improved (β=.27; 95% CI 0.062-0.483), and participants became calmer (β=.98; 95% CI 0.740-1.211) following smartphone-based interventions. Wakefulness did not significantly change from pre- to postsmartphone-based intervention (β=.17; 95% CI -0.081 to 0.412). This was true for both intervention types. There was no interaction effect of intervention type with change in good-bad mood (β=-.01; 95% CI -0.439 to 0.417), calmness (β=.22; 95% CI -0.228 to 0.728), or wakefulness (β=.14; 95% CI -0.354 to 0.644). Experience of presence (β=.34; 95% CI 0.271-0.417) and vitality (β=.35; 95% CI 0.268-0.426) increased from pre- to postsmartphone-based intervention, while experience of burden decreased (β=-0.40; 95% CI -0.481 to 0.311). Again, these effects were present for both intervention types. There were no significant interaction effects of intervention type with pre- to postintervention changes in experience of presence (β=.14; 95% CI -0.104 to 0.384), experience of vitality (β=.06; 95% CI -0.152 to 0.265), and experience of burden (β=-.16; 95% CI -0.358 to 0.017). Our results suggest that both smartphone-based audio-guided bodily interventions and fairy tales have the potential to improve the mood of cancer survivors. ClinicalTrials.gov NCT03707548; https://clinicaltrials.gov/study/NCT03707548. RR2-10.1186/s40359-019-0357-1.


Knowledge of Human Papillomavirus and Acceptability to Vaccinate in Adolescents and Young Adults of the Moroccan Population.
Human papillomavirus (HPV) infection is estimated to play an etiologic role in 99.7% of cervical cancer. Vaccines can prevent up to 70% of the cervical cancer caused by HPV 16 and 18. The present study was designed to define the knowledge of HPV and HPV vaccine acceptability among Moroccan youth. DESIGN, SETTING, PARTICIPANTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: A nationwide anonymous questionnaire with a sample of 688 adolescents (12-17 years) and 356 young adults (18-30 years) was organized, that asked about HPV, origin of cervical cancer, Papanicolaou (Pap) test, and acceptability of HPV vaccine. Data were analyzed using univariate and multivariate logistic regression methods. Overall, a low frequency (213/1044 = 20%) of HPV knowledge was observed among the studied population. A multivariate model analysis showed that age, educational level, and knowledge of the Pap test remained significantly associated factors with HPV knowledge. Additionally, only 27% (282/1044) of participants were willing to accept HPV vaccination. Highest acceptability was observed among young adults compared with adolescents (166/356 = 46.6% vs 116/688 = 16.9%). Sixty-two percent (103/165) of male participants accepted the HPV vaccine compared with only 20.4% (179/879) of female participants. Educational level, type of school, and knowledge of the Pap test were associated factors with HPV vaccine acceptability in a multivariate model analysis. The present study showed a low level of HPV knowledge and HPV vaccine acceptability among Moroccan youth. Promotion of activities and sensitization are required to maximize public awareness in the future. This objective can be achieved with the use of media, active efforts by health care providers, and introduction of sexual education in school programs.


Generation of high-valent iron-oxo porphyrin cation radicals on hemin loaded carbon nanotubes for efficient degradation of sulfathiazole.
Hemin has attracted considerable interest as an efficient catalyst recently, however, its direct application is inefficient due to severe molecular aggregation. Immobilizing hemin on various supports is a feasible approach to address this issue. In this work, a CNTs-hemin catalyst was prepared by loading hemin onto multiwalled carbon nanotubes (CNTs) through ball milling. Compared with hemin, CNTs-hemin demonstrates remarkably enhanced performance in the peroxymonosulfate system, with a 650-fold improvement of apparent rate constant, reaching 97.8% degradation of sulfathiazole in 5 min. High-valent iron-oxo porphyrin cation ((Porp)+•FeIV=O) radicals are proposed as the dominant reactive species in the CNTs-hemin/peroxymonosulfate system instead of sulfate radicals (SO4•-), hydroxyl radicals (•OH), superoxide radicals (O2•-) and singlet oxygen (1O2). More in-depth mechanisms reveal that the strong electron transfer between CNTs and hemin promotes the generation of (Porp)+•FeIV=O radicals through a heterolysis pathway. This research enriches the understanding of the catalytic mechanism of supported biomimetic catalysts for PMS activation and provides a perspective on the role of support materials for catalytic activity.


Gangliocytic paraganglioma leading to duodeno-jejunal intussusception: A case report.
The intussusception of the small bowel is rarely encountered in adult patients and is frequently associated with a lead point that is often malignant. In a 69-year-old female patient with an episode of gastrointestinal (GI) bleeding, computed tomography (CT) showed a duodenal-jejunal intussusception caused by an intraluminal mass. Open polypectomy and reduction of intussusception were performed and the diagnosis of gangliocytic paraganglioma was made at pathological evaluation. It would be important to consider neoplasms like gangliocytic paraganglioma in the setting of adult small bowel intussusception.


The 100 most-cited manuscripts in epilepsy epigenetics: a bibliometric analysis.
The top citation article reflects the developmental milestone of a given field. The purpose of this bibliometric analysis was to identify and assess the 100 most-cited (T100) articles on the epigenetics mechanism of epilepsy. The Web of Science Core Collection (WoSCC) database was used to investigate, and search terms related to epilepsy epigenetics were compiled. Results were ranked according to citation number. The publication year, citation density, authorship, journal, country, institution, manuscript type, theme, and clinical topics were further evaluated. The Web of Science search returned a total of 1231 manuscripts. The number of citations for a manuscript ranges from 739 to 75. The greatest number of manuscripts in the top 100 was published in the Human Molecular Genetics and Neurobiology of Disease (n = 4). The journal with the highest 2021 impact factor was Nature Medicine (IF = 87.244). The most-cited paper by Aid et al. reported a new nomenclature for mouse and rat BDNF gene and its expression profiles. Most manuscripts were original articles (n = 69), of which 52 (75.4%) report findings of basic scientific work. The most prevalent theme was microRNA (n = 29), and the most popular clinical topic was temporal lobe epilepsy (n = 13). The research on the epigenetics mechanism of epilepsy was in its infancy but full of potential. The developmental history and current achievements of hot themes, including microRNA, DNA methylation, and temporal lobe epilepsy, were overviewed. This bibliometric analysis provides useful information and insight for researchers when launching new projects.


Present features of gallstones in Japan. A collective review of 2,144 cases.
A collective review of 2,144 patients operated on for cholelithiasis during the last twenty-two months has shown that younger Japanese adults have predominantly cholesterol stones in their gallbladders and that elderly persons still frequently have bilirubin stones not only in their gallbladders but also in their common bile ducts. Recent westernization of dietary habits in Japan is considered to be the most probable factor causing the increased incidence of cholesterol stones. The decreased incidence of bilirubin stones is considered to be caused by the decreased incidence of biliary infection and increased intake of proteins in food.


[Bilateral lichen aureus. Report of a clinical case].
A case of Lichen aureus in a 15-year old boy is presented. The case is particularly underlined due to lesions on both legs.


Religious beliefs and practices in pregnancy and labour: an inductive qualitative study among post-partum women in Ghana.
Religiosity in health care delivery has attracted some attention in contemporary literature. The religious beliefs and practices of patients play an important role in the recovery of the patient. Pregnant women and women in labour exhibit their faith and use religious artefacts. This phenomenon is poorly understood in Ghana. The study sought to investigate the religious beliefs and practices of post-partum Ghanaian women. A descriptive phenomenological study was conducted inductively involving 13 women who were sampled purposively. Individual in-depth interviews were conducted in English, Ga, Twi and Ewe. The interviews were audio-taped and transcribed. Concurrent analysis was done employing the principles of content analysis. Ethical approval was obtained for the study and anonymity and confidentiality were ensured. Themes generated revealed religious beliefs and practices such as prayer, singing, thanksgiving at church, fellowship and emotional support. Pastors' spiritual interventions in pregnancy included prayer and revelations, reversing negative dreams, laying of hands and anointing women. Also, traditional beliefs and practices were food and water restrictions and tribal rituals. Religious artefacts used in pregnancy and labour were anointing oil, blessed water, sticker, blessed white handkerchief, blessed sand, Bible and Rosary. Family influence and secrecy were associated with the use of artefacts. Religiosity should be a key component of training health care professionals so that they can understand the religious needs of their clients and provide holistic care. We concluded that pregnant women and women in labour should be supported to exercise their religious beliefs and practices.


Skin transcriptome profiles associated with black- and white-coated regions in Boer and Macheng black crossbred goats.
To increase the current understanding of the gene-expression profiles in different skin regions associated with different coat colors and identify key genes for the regulation of color patterns in goats, we used the Illumina RNA-Seq method to compare the skin transcriptomes of the black- and white-coated regions containing hair follicles from the Boer and Macheng Black crossbred goat, which has a black head and a white body. Six cDNA libraries derived from skin samples of the white-coated region (n = 3) and black-coated region (n = 3) were constructed from three full-sib goats. On average, we obtained approximately 76.5 and 73.5 million reads for skin samples from black- and white-coated regions, respectively, of which 75.39% and 76.05% were covered in the genome database. A total of 165 differentially expressed genes (DEGs) were detected between these two color regions, among which 110 were upregulated and 55 were downregulated in the skin samples of white- vs. black-coated regions. The results of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses revealed that some of these DEGs may play an important role in controlling the pigmentation of skin or hair follicles. We identified three key DEGs, i.e., Agouti, DCT, and TYRP1, in the pathway related to melanogenesis in the different skin regions of the crossbred goat. DCT and TYRP1 were downregulated and Agouti was upregulated in the skin of the white-coated region, suggesting a lack of mature melanocytes in this region and that Agouti might play a key developmental role in color-pattern formation. All data sets (Gene Expression Omnibus) are available via public repositories. In addition, MC1R was genotyped in 200 crossbred goats with a black head and neck. Loss-of-function mutations in MC1R as well as homozygosity for the mutant alleles were widely found in this population. The MC1R gene did not seem to play a major role in determining the black head and neck in our crossbred goats. Our study provides insights into the transcriptional regulation of two distinct coat colors, which might serve as a key resource for understanding coat color pigmentation in goats. The region-specific expression of Agouti may be associated with the distribution of pigments across the body in Boer and Macheng Black crossbred goats.


Vegetative phase change and shoot maturation in plants.
As a plant shoot develops, it produces different types of leaves, buds, and internodes, and eventually acquires the capacity to produce structures involved in sexual reproduction. Morphological and anatomical traits that change in coordinated fashion at a predictable time in vegetative development allow this process to be divided into several more-or-less discrete phases; the transition between these phases is termed "vegetative phase change." Vegetative phase change is regulated by a decrease in the expression of the related microRNAs, miR156, and miR157, which act by repressing the expression of squamosa promoter binding protein/SBP-like (SBP/SPL) transcription factors. SBP/SPL proteins regulate a wide variety of processes in shoot development, including flowering time and inflorescence development. Answers to long-standing questions about the relationship between vegetative and reproductive maturation have come from genetic analyses of the transcriptional and posttranscriptional regulatory networks in which these proteins are involved. Studies conducted over several decades indicate that carbohydrates have a significant effect on phase-specific leaf traits, and recent research suggests that sugar may be the leaf signal that promotes vegetative phase change.


Archiving of mutations in HIV-1 cellular reservoirs among vertically infected adolescents is contingent with clinical stages and plasma viral load: Evidence from the EDCTP-READY study.
Globally, HIV-related adolescent deaths have increased about 50%, especially for those who are vertically infected. This could be driven by archived drug resistance mutations (DRMs) as children grow up, which might jeopardize antiretroviral therapy (ART). Our objective was to compare HIV-1 genotypic variation between plasma RNA and proviral DNA of vertically infected adolescents (aged 10-19 years) failing ART. A comparative study was conducted in 2019 among 296 adolescents with perinatal HIV infection (ALPHI) failing ART in health facilities of the Centre Region of Cameroon. The WHO clinical stage, CD4 count and plasma viral load (PVL) were measured. For those failing ART (PVL ≥ 1000 copies/mL), RNA (plasma) and proviral DNA (buffy coat) were sequenced in the pol gene at Chantal BIYA International Reference Centre (CIRCB), Yaoundé, Cameroon. HIV-1 subtypes and DRMs were interpreted using Stanford HIVdb v.8.8 and MEGA-X. Of the 30% (89/296) failing ART, 81 had both RNA and DNA sequences generated and three were excluded for APOBEC mutations: the mean age was 16 ± 3 years; female-to-male ratio was 3:5; median PVL was 46 856 copies/mL [interquartile range (IQR): 19 898-271 410]; median CD4 count was 264 cells/μL (IQR: 131-574); and 42% were at WHO clinical stage 3/4. Subtype concordance between RNA and DNA viral strains was 100%, with CRF02_AG being predominant (65%) and two potential new recombinants found (A1/G/K; F1/G). Adolescents with DRMs were significantly higher in plasma than in proviral DNA (92% vs. 86%, p < 0.0001). Prevalent DRMs by drug class (RNA vs. DNA respectively) were at position M184 (74% vs. 67%) for nucleoside reverse transcriptase inhibitors (NRTIs), K103 (63% vs. 59%) for non-NRTIs, and V82, L76 and M46 (2% vs. 2%) for protease inhibitors. A total of 35% (27/78) of adolescents had concordant DRM profiles in RNA and DNA, while 27% (21/78) had DRMs only in proviral DNA. The presence of archived DRMs was associated with advanced clinical stage 3/4 (OR = 0.14, p = 0.0003) and PVL < 5 Log (Copies/mL) (OR: 4.88, p = 0.006). Although plasma RNA remains more sensitive for detecting HIV-1 DRMs, about a quarter of ALPHI experiencing ART failure in an African setting might have archived DRMs in viral reservoirs, indicating clinically occult resistance. Thus, to ensure effective ART success, proviral DNA profiling (alongside RNA genotyping) would provide additional DRMs for adolescents with advanced clinical stages and/or moderate PVL.


Water-soluble conjugated polyelectrolyte brush encapsulated rare-earth ion doped nanoparticles with dual-upconversion properties for multicolor cell imaging.
A concise route to prepare water-soluble rare-earth ion doped upconversion nanoparticles (UCNPs) by encapsulation of grafted cationic conjugated polyelectrolyte brushes (PFNBr) is reported. Integrating two kinds of upconversion materials effectively addresses multicolor fluorescence by introducing the concept of dual-upconversion.


Irradiation and bleomycin in the treatment of inoperable vulval carcinoma.
Fifteen patients with inoperable squamous cell carcinoma of the vulva were treated with Bleomycin and irradiation. Only 2 patients were also treated with vulvectomy and bilateral lymphadenectomy 2 weeks later. One patients survived more than 4 years without signs of recurrence, another survived 2 1/2 years and 2 more 18 and 12 months respectively. The rest died less than 6 months after the treatment. Three patients developed signs of lung fibrosis. Bleomycin and irradiation may render a tumor operable, but in most cases this regime merely aims at palliation.


A genetic study of two French Guiana Amerindian populations. I. Serum proteins and red cell enzymes.
Phenotypes and gene frequencies are presented for 20 serum and erythrocyte proteins in two Amerindian populations of inner French Guiana. No genetic variability was detected in 12 of these systems. Heterozygosity was calculated for the others and the reasons for its variation are discussed.


Poor prognosis acute myelogenous leukemia: 1 - response to treatment with high dose cytarabine/mitoxantrone/ethyol @ (Amifostine).
Twenty patients with poor prognosis AML and four patients in the blastic phase of a myeloproliferative disorder were treated with two 'pulses' of therapy each consisting of two doses of high dose araC (separated by 12 h) followed by a single dose of mitoxantrone. The pulses were separated by 96 h. Amifostine was then administered tiw. The median age of the population was 68 years with 88% of patients having had either a prior MDS, MPD or toxic exposure. The acute leukemia of 58% of patients either entered a CR or reverted to preleukemic state. For patients under 70 years of age, treatment produced 62% CRs with a leukemia free decision marrow in 77%. For patients over 70 years the CR rate was 27% with 36% of patients having a leukemia free decision marrow.


Cerebrospinal fluid glutamate inversely correlates with positive symptom severity in unmedicated male schizophrenic/schizoaffective patients.
Recent hypotheses have suggested that diminished brain glutamate may be of importance in the neurochemical basis of schizophrenia. We assayed cerebrospinal fluid for glutamate and obtained clinical symptom ratings in 19 medication-free (except p.r.n. chloral hydrate) schizophrenic or schizoaffective (typically with significant schizophrenic qualities) male inpatients. Ratings of positive symptoms were significantly inversely correlated (rs = -.457, p < .05, one-tailed test) with glutamate concentrations. Hallucinatory behavior was strongly correlated (rs = -.621, p < .01, one-tailed test) with glutamate. A subset of 11 patients consented to a second lumbar puncture (LP) after treatment with haloperidol (typically 15 or 20 mg/day) for 2-4 weeks. Haloperidol treatment did not alter glutamate concentrations. No correlations were noted between glutamate and symptoms in the medicated subsample. Though approximately half the patients received chloral hydrate during the 72 hours prior to the unmedicated LP, the correlations between positive symptoms and glutamate in the patients who received no chloral hydrate prior to the LP were quite similar to those found in the overall sample. The results provide further support for the potential importance of glutamate in the neurochemical basis of schizophrenia.


Palmoplantar epidermoid cysts: two cases and brief review of the literature.
Palmoplantar epidermoid cysts can range in clinical presentation from an asymptomatic slowly enlarging mass to a painful nodule. We report two cases: an epidermoid cyst on the sole and another on the palm. This article reviews the possible etiology, diagnosis, and prognosis of palmoplantar epidermoid cysts.


Basilar membrane motion in the pigeon measured with the Mössbauer technique.
Vibration measurements were made of the basilar membrane (BM), limbi and columella footplate (CFP) of pigeon using the Mössbauer technique. Recordings were located at 0.23-1.33 mm from the basal end of the BM. The existence of a travelling wave mode, propagating from base to apex, was established for papillae in apparently good physiological condition. For these papillae the characteristic frequency (CF) of the BM isovelocity (0.08 mm X s-1) response was an exponential function of distance with a frequency mapping constant of 0.91 +/- 0.10 mm (equivalent to 0.63 +/- 0.07 mm X oct-1); BM CF at the base was 5.95 +/- 0.65 kHz. Travelling wave motion was not demonstrated for papillae in poor physiological condition; tonotopy of BM CF was still evident, although the correlation with distance was less (1.08 +/- 0.30 mm X oct-1; 4.35 +/- 0.73 kHz at the base). BM motion was linear and the isovelocity responses were less sensitive and less sharp than single unit threshold tuning curves: for papillae in good physiological condition the SPL at BM CF at 0.08 mm X s-1 was 51 +/- 6 dB SPL; Q10 dB was 1.24 +/- 0.38; high- and low-frequency slopes were 20 +/- 6 dB X oct-1 and -14 +/- 4 dB X oct-1, respectively. The response of the BM relative to the CFP for papillae in good physiological condition was reminiscent of a second order resonant system with damping constant of 0.33 +/- 0.06 and group delay at BM CF of 0.89 +/- 0.36 periods.


Dimensional variability of orthodontic slots and archwires: an analysis of torque expression and clinical implications.
The loss of third-order information in pre-adjusted brackets due to torsional play is a problem in clinical orthodontics. The aim of this study was to evaluate the impact of slot height, archwire height, width and edge bevel's radius on the torsional play for three brackets/archwire systems. Ninety brackets with a 0.022 × 0.028 in. slot with McLaughlin-Bennett-Trevisi prescription from three different manufacturers were selected, and the slot's height and depth were measured using a profile projector. Sixty stainless-steel rectangular archwires from three different manufacturers were sectioned and observed with a SEM to measure their height, width, and radius of edge bevel. The recorded data were used to calculate the theoretical torsional play between different slot-archwire combinations. One-way ANOVA was used to compare the measurements within different bracket types and among different manufacturers. Slot height was usually oversized. Archwire's height was usually undersized, but oversized wires were also observed. The radius edge bevel was the most variable parameter. A certain degree of torsional play is always present that differs from one bracket type to another of the same producer and that can even be doubled from one manufacturer to another. Due to production tolerance, differences between the nominal values and the real dimensions of any components of a slot/archwire system are common. This results in a torsional play that limits torque expression. The archwire's edge bevel plays an important role in torque expression, and clearer information should be provided by the manufacturers regarding this aspect.


Determination of the RNA secondary structure that regulates lysis gene expression in bacteriophage MS2.
The lysis gene of the RNA bacteriophage MS2 is not expressed unless translation of the overlapping coat gene takes place. To understand the molecular basis for this translational coupling the RNA secondary structure around the lysis gene start was analyzed with structure-specific enzymes and chemicals. The existence of a hairpin between nucleotides 1636 and 1707 is in agreement with the structural mapping data and also with the conservation of base-pairing in the related M12 phage. In this hairpin, the G residues in the Shine and Dalgarno region and start codon are inaccessible to RNase T1, which is consistent with the fact that ribosomal access to the lysis gene is blocked when there is no coat gene translation. Deletions or point mutations that are predicted to destabilize the hairpin give rise to lysis protein synthesis that is independent of coat gene translation. Base substitutions that are not expected to weaken the helix do not lead to independent lysis gene expression. Finally, nucleotide changes that strengthen the hairpin lead neither to uncoupled nor to coupled synthesis of the lysis protein. Structural analysis of mutant MS2 RNA shows that small changes in the stability of the secondary structure lead to substantial differences in translation initiation. The function of the hairpin structure in coupling lysis gene to coat gene translation requires that its stability is kept within narrow limits.


CD11b+ and Sca-1+ Cells Exert the Main Beneficial Effects of Systemically Administered Bone Marrow-Derived Mononuclear Cells in a Murine Model of Mixed Th2/Th17 Allergic Airway Inflammation.
Systemic administration of bone marrow-derived mononuclear cells (BMDMCs) or bone marrow-derived mesenchymal stromal cells (MSCs) reduces inflammation and airway hyperresponsiveness (AHR) in a murine model of Th2-mediated eosinophilic allergic airway inflammation. However, since BMDMCs are a heterogeneous population that includes MSCs, it is unclear whether the MSCs alone are responsible for the BMDMC effects. To determine which BMDMC population(s) is responsible for ameliorating AHR and lung inflammation in a model of mixed Th2-eosinophilic and Th17-neutrophilic allergic airway inflammation, reminiscent of severe clinical asthma, BMDMCs obtained from normal C57Bl/6 mice were serially depleted of CD45, CD34, CD11b, CD3, CD19, CD31, or Sca-1 positive cells. The different resulting cell populations were then assessed for ability to reduce lung inflammation and AHR in mixed Th2/Th17 allergic airway inflammation induced by mucosal sensitization to and challenge with Aspergillus hyphal extract (AHE) in syngeneic C56Bl/6 mice. BMDMCs depleted of either CD11b-positive (CD11b+) or Sca-1-positive (Sca-1+) cells were unable to ameliorate AHR or lung inflammation in this model. Depletion of the other cell types did not diminish the ameliorating effects of BMDMC administration. In conclusion, in the current model of allergic inflammation, CD11b+ cells (monocytes, macrophages, dendritic cells) and Sca-1+ cells (MSCs) are responsible for the beneficial effects of BMDMCs. This study shows that bone marrow-derived mononuclear cells (BMDMCs) are as effective as bone marrow-derived mesenchymal stromal cells (MSCs) in ameliorating experimental asthma. It also demonstrates that not only MSCs present in the pool of BMDMCs are responsible for BMDMCs' beneficial effects but also monocytes, which are the most important cell population to trigger these effects. All of this is in the setting of a clinically relevant model of severe allergic airways inflammation and thus provides further support for potential clinical use of cell therapy using MSCs, BMDMCs, and also adult cells such as monocytes in patients with severe asthma.


Eggshell recycling for fabrication of Pd@CaO, characterization and high-performance solar photocatalytic activity.
Recycling of waste materials into useful products is a promising strategy for environmental protection. Eggshell is one of the globally produced huge wastes. In this work, calcium oxide (CaO) nanoparticles were recycled via calcination of chicken eggshells at 1100 °C for 2 h. A novel nanocomposite, made of loading palladium nanoparticles on calcium oxide surface (Pd@CaO), is successfully fabricated through solid-solid interaction. The materials were characterized using different physicochemical techniques: Fourier-transform infrared spectroscopy (FT-IR), ultraviolet-visible spectroscopy (UV-Vis), photoluminescence (PL) analysis, ultra-high resolution field emission scanning electron microscope (FE-SEM), transmittance electron microscope (TEM), and X-ray diffraction (XRD). The study sheds light on the ability of the materials to be used for detoxification of crystal violet dye as pollutant model under solar irradiation. The effects of operational conditions, such as catalyst mass, initial dye concentration, pH, and illumination time, have been tested. The optimum conditions for crystal violet photocatalytic degradation in the presence of Pd@CaO were mild conditions. Control experiments studied the effect of sunlight in the absence of the catalyst, and the effect of the catalyst in the absence of sunlight does not provide the significant removal exhibited in the presence of catalyst under solar irradiation.


Expression of gonadotropin subunit genes following 4-nonylphenol exposure in masu salmon: effects on transcript levels and promoter activities via estrogen receptor alpha.
The 4-nonylphenol (NP) group is classified as some of the most potent endocrine disrupting chemicals (EDCs) reported to have estrogenic effects on reproductive endocrine system in vertebrates. In the present study, we investigated the effect of NP on expression of gonadotropin (GTH) subunit genes in masu salmon (Oncorhynchus masou) to clarify pituitary-based reproductive impact by EDCs. Female juvenile fish were injected with NP (a mixture of ring and chain isomers; 10 or 50 mg kg(-1) body weight) and maintained for 3 days post-injection. A semi-quantitative reverse transcription-polymerase chain reaction was used to analyze the pituitary GTHalpha, follicle-stimulating hormone beta (FSHbeta), and luteinizing hormone beta (LHbeta), and hepatic vitellogenin (VTG) mRNA levels. A low dose of NP induced the GTHalpha and LHbeta mRNA levels. High dose of NP slightly reduced FSHbeta mRNA levels in contrast to increased VTG mRNA levels. In a promoter study, NP (1-10 nM) increased the activities of luciferase reporter gene located downstream of masu salmon GTHalpha or LHbeta 5'-flanking region depending on the estrogen receptor alpha (ERalpha) in transiently transfected mammalian cells. In contrast, the luciferase activity of FSHbeta was elevated by NP in an ERalpha-independent manner. These results suggest that GTH subunit gene expression of masu salmon may be affected by EDCs at the transcription level and that the genes are useful markers for pituitary effects of xenoestrogens.


Evaluation of spatial R maximum cardiac vector changes in exercise testing: pre-exercise versus post-exercise measurements.
R wave amplitude changes during exercise have been a controversial issue as both increase and decrease in amplitude have been reported in patients with coronary arterial disease. This variability in response is attributed to change in position and heart axis on exercise. In view of this limitation, this study evaluated the change in spatial R maximum amplitude on exercise, which should not be affected by the above factors. Twenty patients with ischaemic heart disease (male 20, age 38-61 years) and 9 control subjects (male 9, age 32-65 years) were studied. Orthogonal leads, X, Y, Z were recorded using corrected Frank lead system on a stereokinematic vectorcardiograph (Tonnies). The magnitude of spatial R maximum cardiac vector increased from 0.1 to 0.6 mV in 8/9 control subjects and decreased or showed no change in 18 of the 20 patients with coronary arterial disease. In the control group, the mean value at the end of exercise (0.98 +/- 0.34 mV) was significantly less (P less than 0.01) as compared to pre-exercise value (1.09 +/- 0.2 mV). Our preliminary observations thus indicate that, with exercise, the magnitude of spatial R maximum cardiac vector decreases or shows no alteration in height in patients with coronary arterial disease whereas it increases in normal subjects.


Silver nanoparticles loaded graphene-poly-vinylpyrrolidone composites as an effective recyclable antimicrobial agent.
Silver nanoparticles (AgNPs) are often used as antibacterial agents. Here, graphene-silver nanoparticles (G-Ag) and graphene-silver nanoparticles poly-vinylpyrrolidone (G-AgPVPy) were prepared by chemical reduction and in-situ polymerization of vinylpyrrolidone (VPy). The prepared G-Ag and G-AgPVPy composites were characterized using various techniques. The size of the AgNPs on the graphene surface in the prepared G-Ag and G-AgPVPy composites was measured as ∼20 nm. The graphene sheets size in the G-Ag and G-AgPVPy composites were measured as 6.0-2.0 μm and 4.0-0.10 μm, respectively, which are much smaller than graphene sheets in graphite powder (GP) (10.0-3.0 μm). The physicochemical analysis confirmed the formation of G-Ag and G-AgPVPy composites and even the distribution of AgNPs and PVPy on the graphene sheets. The synthesized composites (G-AgPVPy, G-Ag) exhibited a broad-spectrum antibacterial potential against both Gram-negative and Gram-positive bacteria. The lowest minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values were calculated as >40 μg/mL using G-Ag and GP, while G-AgPVPy showed as 10 μg/mL against Staphylococcus aureus. Among GP, G-Ag, and G-AgPVPy, G-AgPVPy disturbs the cell permeability, damages the cell walls, and causes cell death efficiently. Also, G-AgPVPy was delivered as a significant reusable antibacterial potential candidate. The MIC value (10 μg/mL) did not change up to six subsequent MIC analysis cycles.


Assessment of clinically actionable pharmacogenetic markers to stratify anti-seizure medications.
Epilepsy treatment is challenging due to heterogeneous syndromes, different seizure types and higher inter-individual variability. Identification of genetic variants predicting drug efficacy, tolerability and risk of adverse-effects for anti-seizure medications (ASMs) is essential. Here, we assessed the clinical actionability of known genetic variants, based on their functional and clinical significance and estimated their diagnostic predictability. We performed a systematic PubMed search to identify articles with pharmacogenomic (PGx) information for forty known ASMs. Functional annotation of the identified genetic variants was performed using different in silico tools, and their clinical significance was assessed using the American College of Medical Genetics (ACMG) guidelines for variant pathogenicity, level of evidence (LOE) from PharmGKB and the United States-Food and drug administration (US- FDA) drug labelling with PGx information. Diagnostic predictability of the replicated genetic variants was evaluated by calculating their accuracy. A total of 270 articles were retrieved with PGx evidence associated with 19 ASMs including 178 variants across 93 genes, classifying 26 genetic variants as benign/ likely benign, fourteen as drug response markers and three as risk factors for drug response. Only seventeen of these were replicated, with accuracy (up to 95%) in predicting PGx outcomes specific to six ASMs. Eight out of seventeen variants have FDA-approved PGx drug labelling for clinical implementation. Therefore, the remaining nine variants promise for potential clinical actionability and can be improvised with additional experimental evidence for clinical utility.


The Role of Hysteroscopic and Robot-assisted Laparoscopic Myomectomy in the Setting of Infertility.
Fibroids, the most common gynecologic condition in women of reproductive age, have traditionally been treated with hysterectomy. As more women delay childbearing, myomectomy becomes an essential component of the gynecologist's armamentarium. Minimally invasive approaches to myomectomy have been shown to decrease morbidity and reduce care-related costs, while improving reproductive outcomes. Hysteroscopic myomectomy is a reproducible and easily learned technique for the treatment of submucosal fibroids. Robot-assisted laparoscopic myomectomy overcomes most of the technical challenges of laparoscopic myomectomy for intramural and subserosal fibroids. The combined adoption of these technologies will allow more patients with fibroids to benefit from a minimally invasive approach.


Maternal transfer of organochlorine compounds to oocytes in wild and farmed gilthead sea bream (Sparus aurata).
To investigate the transfer of lipophilic organochlorine compounds to the gonads in gilthead sea bream females, liver and oocytes from wild and farmed females, just before spawning, were analysed by gas chromatography coupled to tandem mass spectrometry after clean-up of the fatty extracts by normal phase HPLC. This analytical methodology allowed us to achieve limits of detection of around 0.1 ng/g. Data obtained show that the chemicals studied are transferred from the liver to oocytes in ratios up to 0.51. In general this means that less than a half of pollutant load is transferred from liver to oocytes. A significant correlation (p<0.05) between log K(ow) and ratios (oocytes/liver) was found. Compounds with larger Log K(ow) present lower lipid-based concentration ratios (oocytes/liver). We have inferred that the reason the fugacity model is not accomplished is specifically dependent on the vitellogenesis process, which involves the transfer of lipids from the liver to oocytes in teleostei. No significant differences (t-Student) have been found between wild and farmed females transfer ratios (oocytes/liver).


Analysis of artesunic acid and dihydroqinghaosu in blood by high-performance liquid chromatography with reductive electrochemical detection.
A new high-performance liquid chromatography (HPLC) method using reductive electrochemical detection has been developed for the analysis of the antimalarial drugs artesunic acid (ARTS) and dihydroqinghaosu (DQHS) in blood. Presently, this method has been validated to 4 micrograms/ml for ARTS and 200 ng/ml for DQHS. Pharmacokinetic studies in the rabbit show that after intravenous administration (100 mg/kg) ARTS is metabolized rapidly to DQHS and has a t1/2 of 1.7 min in blood. DQHS data were fit to non-linear regression models consisting of the sum of two exponential terms. For phases 1 and 2, t1/2 values of 3.0 +/- 0.4 and 29 +/- 2 min were calculated, respectively. In vitro studies in which ARTS was incubated with blood from various species show that rabbit blood hydrolyzes ARTS at a much greater rate than rat or human blood. Incubation of ARTS with rabbit blood in the presence or absence of diisopropylfluorophosphate suggested that this hydrolysis reaction is catalyzed by plasma and red blood cell esterases. These results suggest that future pharmacokinetic studies in both animals and man should focus on the measurement of DQHS rather than ARTS.


A review of the genera Cleigastra Macquart, Gonarcticus Becker, Gonatherus Rondani, Hexamitocera Becker, Nanna Strobl, Orthacheta Becker and Spathephilus Becker (Diptera, Scathophagidae) of Russia.
Flies of the genera Cleigastra Macquart, 1835, Gonarcticus Becker, 1894, Gonatherus Rondani, 1856, Hexamitocera Becker, 1894, Nanna Strobl, 1894, Orthacheta Becker, 1894 and Spathephilus Becker, 1894 (all Scathophagidae) of the fauna of Russia are reviewed. Key to genera, generic descriptions and keys for determination of species are given, and data on geographical distribution are summarized. One species, Nanna cryophila sp. nov., is described as new to science. One new synonymy is proposed: Nanna kamtschatkense (Hendel, 1930) = Nanna tibiella (Zetterstedt, 1838). Orthacheta cornuta (Loew, 1863) is recorded from Europe for the first time. Gonarcticus arcticus (Becker, 1907) is newly recorded from the Palaearctic Region and Russia. Additionally, Nanna flavipes (Fallén, 1819) is newly recorded from China, and Spathephilus nigriventris (Loew, 1864) is newly recorded from Kazakhstan.


Cobalt and nickel content in Hydrocharis morsus-ranae and their bioremoval from single- and binary solutions.
Aquatic macrophytes are known to remove trace metals from surrounding water. In the present study, an attempt was made to evaluate the phytofiltration capacity of Hydrocharis morsus-ranae and to show competition between cobalt (Co) and nickel (Ni) for the better understanding of metal bioaccumulation in the species. In a laboratory experiment, H. morsus-ranae was exposed to separate (single) and binary solutions of these metals: Ni 10.7, 18.7, 32.7, 57.1, and 100 (μg L-1); Co 5.33, 9.32, 16.3, 28.6, and 50.0 (μg L-1); and 10.7 Ni + 5.33 Co, 18.7 Ni + 9.32 Co, 32.7 Ni + 16.3 Co, 57.1 Ni + 28.6 Co, 100 Ni + 50.0 Co (μg L-1). The content of Co and Ni in the plant increased with the increasing concentration in the growth medium. Competition between the metals was seen during uptake in binary solutions. Ni interfered with the accumulation of Co, resulting in a lower Co content than in plants cultivated in Co solutions. A particularly high Co content (up to 155 mg kg-1 dry weight [d.w.]) and high efficiency of Ni uptake (Bioaccumulation Factor (BF) 2572-7239) makes the species a very good accumulator of these metals. The high content of both trace metals in plant tissues (up to 511 mg kg-1 d.w. Ni and 155 mg kg-1 d.w. Co) did not affect its growth, indicating tolerance of these toxicants. The plant showed excellent ability in removing Co (up to 98.6% in solution with 5.33 μg L-1 Co) and Ni (up to 91.4% in solution with 57.1 μg L-1 Ni and 28.6 μg L-1 Co) from nutrient solution. The results suggest that H. morsus-ranae may be useful for the phytoremediation of water bodies contaminated with Co and Ni.


Preventing alloimmunization using a new model for matching extensively typed red blood cells.
Alloimmunization is a well-known adverse event associated with red blood cell (RBC) transfusions, caused by phenotype incompatibilities between donor and patient RBCs that may lead to haemolytic transfusion reactions on subsequent transfusions. Alloimmunization can be prevented by transfusing fully matched RBC units. Advances in RBC genotyping render the extensive typing of both donors and patients affordable in the foreseeable future. However, the exponential increase in the variety of extensively typed RBCs asks for a software-driven selection to determine the 'best product for a given patient'. We propose the MINimize Relative Alloimmunization Risks (MINRAR) model for matching extensively typed RBC units to extensively typed patients to minimize the risk of alloimmunization. The key idea behind this model is to use antigen immunogenicity to represent the clinical implication of a mismatch. Using simulations of non-elective transfusions in Caucasian donor and patient populations, the effect on the alloimmunization rate of the MINRAR model is compared with that of a baseline model that matches antigens A, B and RhD only. Our simulations show that with the MINRAR model, even for small inventories, the expected number of alloimmunizations can be reduced by 78.3% compared with a policy of only matching on antigens A, B and RhD. Furthermore, a reduction of 93.7% can be achieved when blood is issued from larger inventories. Despite an exponential increase in phenotype variety, matching of extensively typed RBCs can be effectively implemented using our MINRAR model, effectuating a substantial reduction in alloimmunization risk without introducing additional outdating or shortages.


The proliferative activity of neurilemomas.
Twenty-one patients with neurilemomas (15 intracranial and 6 intraspinal) received a 1-hour intravenous infusion of 5-bromodeoxyuridine (BrdU), 200 mg/m2 before tumor removal, to label S-phase tumor cells. Excised tumor specimens were stained by the indirect immunoperoxidase method with anti-BrdU monoclonal antibodies to determine the BrdU labeling index, or percentage of S-phase cells. The BrdU labeling index ranged from 0.1% to 3.1% (mean, 0.9%). The BrdU labeling index was greater than 1.5% in four of the 21 tumors (three trigeminal and one spinal). One acoustic tumor in a patient with neurofibromatosis type 1 had a labeling index of 1.3%, which was the highest among the acoustic tumors. The BrdU labeling indices did not correlate with the patient's age, tumor size, or the duration of signs and symptoms. There was no significant difference between the BrdU labeling indices of Antoni type A and Antoni type B tissue. The low BrdU labeling index of most of the intracranial neurilemomas coincides well with the slow growth of these tumors. As the BrdU labeling index may reflect growth potential of individual tumors, it could be used to guide the follow-up patients with incompletely resected tumor.


A novel subtyping of intestinal metaplasia of the stomach, with special reference to the histochemical characterizations of endocrine cells.
Intestinal metaplasia of the stomach was grouped into 3 subtypes (A, B and C) according to the degree of pyloric gland involution which was judged from patterns of paradoxical Concanavalin A staining after Katsuyama and Spicer. The appearance of endocrine cells was investigated with immunohistochemical and silver methods. Type A metaplasia with slightly to moderately atrophic pyloric glands corresponded to the incomplete type in the previous classification, while Type C showing complete disappearance of pyloric glands corresponded to the complete type. Type B with severely atrophic pyloric glands was an intermediate. This subtyping reflects the cell kinetics in the intestinalized mucosa well. Regarding the endocrine cells, their total number varied in the order Type A greater than Type B greater than Type C. The selective populations of the endocrine cells including glicentin-containing cells, Grimelius-positive argyrophil cells without argentaffinity and intestinal-type enterochromaffin cells frequently formed hyperplastic foci in the intestinalized areas, where the other gut-type and proper gastric-type endocrine cells were scarcely noted. Immunoreactivity of glucagon or bovine pancreatic polypeptide were occasionally identified in a subpopulation of the glicentin-containing cells.


Growth hormone secretagogue receptor constitutive activity impairs voltage-gated calcium channel-dependent inhibitory neurotransmission in hippocampal neurons.
Presynaptic CaV 2 voltage-gated calcium channels link action potentials arriving at the presynaptic terminal to neurotransmitter release. Hence, their regulation is essential to fine tune brain circuitry. CaV 2 channels are highly sensitive to G protein-coupled receptor (GPCR) modulation. Our previous data indicated that growth hormone secretagogue receptor (GHSR) constitutive activity impairs CaV 2 channels by decreasing their surface density. We present compelling support for the impact of CaV 2.2 channel inhibition by agonist-independent GHSR activity exclusively on GABA release in hippocampal cultures. We found that this selectivity arises from a high reliance of GABA release on CaV 2.2 rather than on CaV 2.1 channels. Our data provide new information on the effects of the ghrelin-GHSR system on synaptic transmission, suggesting a putative physiological role of the constitutive signalling of a GPCR that is expressed at high levels in brain areas with restricted access to its natural agonist. Growth hormone secretagogue receptor (GHSR) displays high constitutive activity, independent of its endogenous ligand, ghrelin. Unlike ghrelin-induced GHSR activity, the physiological role of GHSR constitutive activity and the mechanisms that underlie GHSR neuronal modulation remain elusive. We previously demonstrated that GHSR constitutive activity modulates presynaptic CaV 2 voltage-gated calcium channels. Here we postulate that GHSR constitutive activity-mediated modulation of CaV 2 channels could be relevant in the hippocampus since this brain area has high GHSR expression but restricted access to ghrelin. We performed whole-cell patch-clamp in hippocampal primary cultures from E16- to E18-day-old C57BL6 wild-type and GHSR-deficient mice after manipulating GHSR expression with lentiviral transduction. We found that GHSR constitutive activity impairs CaV 2.1 and CaV 2.2 native calcium currents and that CaV 2.2 basal impairment leads to a decrease in GABA but not glutamate release. We postulated that this selective effect is related to a higher CaV 2.2 over CaV 2.1 contribution to GABA release (∼40% for CaV 2.2 in wild-type vs. ∼20% in wild-type GHSR-overexpressing cultures). This effect of GHSR constitutive activity is conserved in hippocampal brain slices, where GHSR constitutive activity reduces local GABAergic transmission of the granule cell layer (intra-granule cell inhibitory postsynaptic current (IPSC) size ∼-67 pA in wild-type vs. ∼-100 pA in GHSR-deficient mice), whereas the glutamatergic output from the dentate gyrus to CA3 remains unchanged. In summary, we found that GHSR constitutive activity impairs IPSCs both in hippocampal primary cultures and in brain slices through a CaV 2-dependent mechanism without affecting glutamatergic transmission.


Isolated superior mesenteric venous thrombophlebitis with acute appendicitis.
Isolated superior mesentericveinous thrmbophlebitis is a rarely recognised condition associated with a high morbidity. It usually develops secondary to infection in the drainage area of the portal venous system, like appendix. We report a case of neglected perforated acute appendicitis complicated by superior mesenteric venous pyelephlebitis patiant represented with a vague pain to right of umlicus, which is atypical this why cat scan was done and showed obstructed superiormesentric vein, portal vein was free with acute appendicitis. Appendicectomy and treatment with broad-spectrum antibiotics, anticoagulation, and platelets led to a full recovery. Follow-up imaging after one month revealed complete canalization of superior mesentric vein. Abdominal pain if atypical like our case report need imaging diagnosis. Modern diagnostic imaging techniques help the early diagnosis of acute phase pylephlebitis. CT can detect primary source of infection, extent of pylephlebitis, CT scan is the most reliable initially. Ultrasound scan with color flow Doppler is also a sensitive test for confirming partial patency of the portal vein and portal vein thrombosis accidentally discovered complete obliteration of superior mesenteric vein with thrombosis which remained not propagated by serial Doppler ultrasound of liver. Appropriate treatment should be initiated as soon as possible. To avoid extension to portal vein. The principal treatment for pylephlebitis is to remove the source of infection as appendicectomy. Anticoagulants must be used. Regarding the treatment of portal thrombosis, post operative use of heparin has been advocated. Cat scan play an important role in case of atypical abdominal pain.


Symptomatic Irreversible Pulpitis Induces Increased Levels of Human NLRP3 in Gingival Crevicular Fluid Compared to Saliva: A Case Control Observational Study.
The goal of this case-control observational study was to compare the levels of the human nucleotide-binding domain, leucine-rich repeat, and pyrin domain-containing-3 (NLRP3) protein in the saliva and gingival crevicular fluid (GCF) of patients with symptomatic irreversible pulpitis (SIP) and healthy controls. The 16 patients in the control group were matched with the 16 patients in the SIP group to create a total of 32 patients. In addition to saliva, GCF (n = 48) samples were collected from the involved tooth (n = 16), contralateral tooth (n = 16), and adjacent tooth (n = 16) in the SIP group. Saliva and GCF were taken from the healthy group as a baseline. An independent t-test was used for statistical analysis. The random-intercept model was used to compare the average NLRP3 levels in the SIP tooth, adjacent tooth, and contralateral tooth taking age as a covariate, and the P value was adjusted using Bonferroni correction. There were significantly higher levels of NLRP3 in the saliva of SIP patients (1.78 ± 1.14 ng/ml) compared to the healthy control (0.70 ± 0.70 ng/ml) and in the GCF of the involved tooth (5.72 ± 0.63 ng/ml) compared to healthy people (1.60 ± 0.42 ng/ml) (P < .001). In SIP patients the mean difference of NLRP3 levels between SIP and contralateral teeth was significant at 4.13 ng/ml (95% confidence interval, 3.52-4.70 P < .001) and a mean difference between adjacent teeth and contralateral teeth was significant at 3.53 ng/ml [95% confidence interval, 2.94-4.12 P < .001]. The NLRP3 in GCF and saliva had a negative association in the affected tooth but a negligible correlation in healthy controls. The NLRP3 inflammasome has the potential to be employed as a molecular diagnostic biomarker for pulpal disorders.


Starvation enhances the ability of insulin to inhibit its own secretion.
To examine whether decreased insulin secretion during starvation is related to a change in the ability of insulin to inhibit its own secretion, plasma C-peptide was measured after plasma insulin levels were acutely raised by intravenous (IV) insulin infusion in a dose of 40 and 80 mU/M2/min in obese subjects before and after a 72 hour fast. Plasma glucose concentration was maintained +/- 4% of basal levels by a variable glucose infusion. During the 80 mU infusion, at plasma insulin levels of 200 microU/mL, plasma C-peptide fell by 0.17 pmol/mL in the fed state. In the fasted state, despite basal levels that were 36% lower, C-peptide decreased by 0.21 pmol/mL. Highly significant increases in percent suppression after fasting were noted during both 40 mU and 80 mU studies. The plasma C-peptide response was related to the insulin infusion dose in both the fed and fasted state. In contrast, alpha cell suppression by insulin, as determined by plasma glucagon levels, was not altered by fasting. It is concluded that enhanced inhibitory influences of insulin on the beta cell during starvation may be a physiologically important mechanism for diminished insulin secretion during the transition from the fed to the fasting state.


[Secondary prevention after acute coronary syndrome: therapeutic goals achievement in relation with changes in guidelines].
Secondary prevention is a key strategy for reducing levels of coronary heart disease, but a gap between guidelines and practice remains. The aim of this double-part survey was to evaluate the improvement in secondary prevention one year after acute coronary syndrome (ACS) in real life, between 1999 and 2005, with respect to the change in guidelines. Two surveys of almost similar design were performed in 1999 and 2005-2006. In each survey, unselected consecutive patients suffering from ACS (n=112 hospitalized in 1998, and n=110 in 2004) were evaluated at admission, and one year after hospitalization, for the risk factors, lifestyle, and achievement of therapeutic goals recommended by the most recent guidelines. Follow-up (FU) data were obtained by mail and phone contact with patient, general practitioner and cardiologist, and medical laboratory when appropriate. At 1-year FU (n=192 survivors with FU), smoking cessation (87% in 1999 versus 89% in 2005) and obesity (13% versus 19%, respectively) did not vary significantly. Blood pressure was controlled (< 140/90 mmHg, excepted in diabetics in 2005 with less than 130/80 mmHg) in 65% versus 80% (p<0.03). The rate of patients with no or controlled diabetes mellitus decreased from 1999 to 2005 (90% versus 76%), despite more intensive treatment (insulin in 1% versus 20%).The goals for LDL cholesterol were achieved in 47% of patients in 1999 (< 3.4 mmol/L) and in 76% in 2005 (< 2.6 mmol/L) (p<0.0001). Goals for triglycerides were achieved in 86% in 1999 (< 2g/L), and in 80% in 2005 (< 1.5 g/L) (NS). Besides, 63% of patients received an hypolipemic drug in 1999 (a statin in 59%) and 91% in 2005 (a statin in 88%). Mean number of controlled risk factors was 3.96+/-1.52 in 1999 versus 4.94+/-1.83 in 2005, and prevalence of pts with more than five controlled risk factors at one year FU increased from 15 to 44% (p<0.0001). These results, drawn from unselected consecutive patients managed in real life, demonstrate an improvement in secondary prevention one year after ACS, between 1999 and 2005, despite strengthened guidelines for blood pressure, triglycerides and LDL cholesterol levels. Control of obesity and diabetes remains unoptimal.


Ciliate Biology: The Graceful Hunt of a Shape-Shifting Predator.
Even single-celled eukaryotes are capable of highly complex behaviors. A new study reveals how one unicellular predator actively manipulates and remodels its unique cytoskeletal morphology to achieve rapid shape changes and a remarkable hunting strategy.


Report Automation.
A vascular lab procedure culminates in a diagnostic report that is a combination of the data generated on the vascular lab equipment, physician interpretations, and recommendations. The transcription process can be error prone and inefficient. Computerized capture of data from the equipment and transmission into a reporting system is the definition of "automation" in this article. In this article, we describe an organized approach to collecting data generated on vascular lab equipment and delivering to reporting systems to decrease error and improve efficiency.


Clinical and epidemiological characteristics of 369 patients with pelvic fractures in Eastern Zhejiang Province of China: a retrospective study.
Data on the epidemiological characteristics and prognostic factors of patients with pelvic fractures are lacking, particularly in China. This study aimed to summarise the clinical and epidemiological characteristics of patients with pelvic fractures in eastern Zhejiang Province, China, and to identify risk factors for poor prognosis. The clinical data of 369 patients with pelvic fractures admitted to the Ningbo No. 6 Hospital between September 2020 and September 2021 were retrospectively analysed. Data on the demographic characteristics; fracture classification; injury time, cause, and site; treatment plan; and prognosis were collected using the Picture Archiving and Communication System and the Hospital Information System. Differences in constituent proportions were analysed using the chi-square test. Logistic regression analysis was used to identify factors affecting patient prognosis. Statistical significance was set at p ≤ 0.05. Among the 369 patients, there were 206 men and 163 women, at a ratio of 1.26:1, and the average age was 53.64 ± 0.78 years. More than 50% of patients were aged 41-65 years. The average length of hospital stay was 18.88 ± 1.78 days. The three most common causes of pelvic fractures were traffic accidents (51.2%), falls from height (31.44%), and flat-ground falls (14.09%). There were significant differences in the distribution of the three causes of injury depending on age (p < 0.001), sex (p < 0.001), and occupation (p < 0.0001). Most patients were manual workers (48.8%). Furthermore, most patients (n = 262, 71.0%) underwent surgical treatment for pelvic fractures. Postoperative complications occurred in 26 patients (7.05%), and infection was the main complication (73.08%). Age (p = 0.013), occupation (p = 0.034), cause of injury (p = 0.022), treatment options (p = 0.001), and complications (p < 0.0001) were independent factors affecting the prognosis of patients with pelvic fractures. One death (0.027%) occurred, which was due to severe blood loss. Age, occupation, cause of injury, treatment options and complications were factors affecting patient prognosis. In addition, changes in blood flow and prevention of infection warrant attention.


Electron-microscopical study on senile plaques in Alzheimer's disease.
The cerebral cortex taken post mortem from a case of Alzheimer's disease was examined especially with regard to the relation between blood vessels and senile plaques. Many senile plaques had central cores, composed of such matter as degenerated blood vessels and basement membranes with abundant amyloid fibrils. The components of senile plaques seemed to be degenerated neuronal and glial tissue compressed by developed basement membranes and amyloid fibrils. From this we would like to emphasize that senile plaques seem to be caused by amyloid fibrils and degenerated capillaries.


The influence of compatibility of Si-Ni decoction with metabolism in intestinal bacteria on transports of toxic diterpenoid alkaloids from processed aconite root across Caco-2 monolayers.
In traditional Chinese medicine, processed aconite root (lateral root of Aconitum carmichaelii Debx.) is used as the principle herb of the Si-Ni decoction (SND) formula due to its cardiotonic effect, while its cardiotoxicity and neurotoxicity caused by diester and monoester diterpenoid alkaloids are reduced by compatibility of dried ginger and honey-processed liquorice in SND. To investigate the detoxification of processed aconite root by compatibility of SND from the perspective of intestinal absorption with metabolism in intestinal bacteria. Decoctions of processed aconite root (AD), processed aconite root and honey-processed liquorice (ALD), and SND with the same amount of each herb were prepared, then were incubated in human intestinal bacteria juice (IBJ) in vitro for different durations. Bidirectional transmembrane transports of these decoctions and their IBJ-incubated decoctions were conducted on Caco-2 monolayers. Correlation between efflux ratios changes of benzoylmesaconine, benzoylaconine, benzoylhypaconine (monoester-diterpenoid alkaloids, MDAs) and hypaconitine (diester-diterpenoid alkaloids) from processed aconite root, and metabolic trends of compounds from honey-processed liquorice and dried ginger were also performed. The absorption of MDAs from processed aconite root was increased by combination with honey-processed liquorice in ALD, but they were decreased significantly by the addition of dried ginger in SND. Take benzoylhypaconine for example, the Papp, AP to BL soared from (3.13 ± 0.18) × 10-7 cm/s in AD to (23.32 ± 3.51) × 10-7 cm/s in ALD, while it dropped to (1.12 ± 0.17) × 10-7 cm/s in SND. When herb combined decoctions metabolised by intestinal bacteria for 12 h, the efflux ratio of benzoylhypaconine were both increased from 0.56 to 1.21 in ALD and from 1.10 to 2.61 in SND, which was correlative with the generation of davidigenin and glycyrrhetic acid (the metabolites of chalcones and pentacyclic triterpenoids from liquorice) in ALD and with the metabolism of [6]-gingerol (the major compound from dried ginger) in SND, respectively. Compatibility of SND altered the intestinal absorption of toxic MDAs and hypaconitine from processed aconite root. In SND, dried ginger rather than honey-processed liquorice played the role of detoxification of these toxic compounds in the intestinal absorption. The intestinal detoxification of SND was significantly and strongly correlative with metabolism of dried ginger and honey-processed liquorice by intestinal bacteria, simultaneously.


What is an adequate length of baseline in research and clinical practice with chronic headache?
We examined the representatives of baseline headache diary recording periods of 1, 2, 3, and 4 weeks for three kinds of headache disorder--tension, migraine, and combined migraine and tension. For research purposes at pretreatment, 2 weeks of diary recording are preferable for tension headache, while at least 3 weeks are preferred for migraine and combined headache. At follow-up, 1 week of diary recording appears adequate for all three headache types. Recommendations are also made for clinical practice.


Trans-Planckian philosophy of cosmology.
I provide some philosophical groundwork for the recently proposed 'trans-Planckian censorship' conjecture in theoretical physics. In particular, I argue that structure formation in early universe cosmology is, at least as we typically understand it, autonomous with regards to quantum gravity, the high energy physics that governs the Planck regime in our universe. Trans-Planckian censorship is then seen as a means of rendering this autonomy an empirical constraint within ongoing quantum gravity research.


Ramping up mitosis: an AMPKα2-regulated signaling network promotes mitotic progression.
In the December 23rd issue of Molecular Cell, Banko et al. (2011) describe a chemical genetic screen that identified 28 novel AMPKα2 direct substrates. A subset of these substrates comprise a signaling network by which AMPK, seemingly independent of cellular energy status, promotes mitotic progression.


Assessment of synergistic antibacterial activity of combined biosurfactants revealed by bacterial cell envelop damage.
Besides potential surface activity and some beneficial physical properties, biosurfactants express antibacterial activity. Bacterial cell membrane disrupting ability of rhamnolipid produced by Pseudomonas aeruginosa C2 and a lipopeptide type biosurfactant, BS15 produced by Bacillus stratosphericus A15 was examined against Staphylococcus aureus ATCC 25923 and Escherichia coli K8813. Broth dilution technique was followed to examine minimum inhibitory concentration (MIC) of both the biosurfactants. The combined effect of rhamnolipid and BS15 against S. aureus and E. coli showed synergistic activity by expressing fractional inhibitory concentration (FIC) index of 0.43 and 0.5. Survival curve of both the bacteria showed bactericidal activity after treating with biosurfactants at their MIC obtained from FIC index study as it killed >90% of initial population. The lesser value of MIC than minimum bactericidal concentration (MBC) of the biosurfactants also supported their bactericidal activity against both the bacteria. Membrane permeability against both the bacteria was supported by amplifying protein release, increasing of cell surface hydrophobicity, withholding capacity of crystal violet dye and leakage of intracellular materials. Finally cell membrane disruption was confirmed by scanning electron microscopy (SEM). All these experiments expressed synergism and effective bactericidal activity of the combination of rhamnolipid and BS15 by enhancing the bacterial cell membrane permeability. Such effect of the combination of rhamnolipid and BS15 could make them promising alternatives to traditional antibiotic in near future.


Immunotherapy-related adverse events in real-world patients with advanced non-small cell lung cancer on chemoimmunotherapy: a Spinnaker study sub-analysis.
The Spinnaker study evaluated survival outcomes and prognostic factors in patients with advanced non-small-cell lung cancer receiving first-line chemoimmunotherapy in the real world. This sub-analysis assessed the immunotherapy-related adverse effects (irAEs) seen in this cohort, their impact on overall survival (OS) and progression-free survival (PFS), and related clinical factors. The Spinnaker study was a retrospective multicentre observational cohort study of patients treated with first-line pembrolizumab plus platinum-based chemotherapy in six United Kingdom and one Swiss oncology centres. Data were collected on patient characteristics, survival outcomes, frequency and severity of irAEs, and peripheral immune-inflammatory blood markers, including the neutrophil-to-lymphocyte ratio (NLR) and systemic immune-inflammation index (SII). A total of 308 patients were included; 132 (43%) experienced any grade irAE, 100 (32%) Grade 1-2, and 49 (16%) Grade 3-4 irAEs. The median OS in patients with any grade irAES was significantly longer (17.5 months [95% CI, 13.4-21.6 months]) than those without (10.1 months [95% CI, 8.3-12.0 months]) (p<0.001), either if Grade 1-2 (p=0.003) or Grade 3-4 irAEs (p=0.042). The median PFS in patients with any grade irAEs was significantly longer (10.1 months [95% CI, 9.0-11.2 months]) than those without (6.1 months [95% CI, 5.2-7.1 months]) (p<0.001), either if Grade 1-2 (p=0.011) or Grade 3-4 irAEs (p=0.036). A higher rate of irAEs of any grade and specifically Grade 1-2 irAEs correlated with NLR <4 (p=0.013 and p=0.018), SII <1,440 (p=0.029 ad p=0.039), response to treatment (p=0.001 and p=0.034), a higher rate of treatment discontinuation (p<0.00001 and p=0.041), and the NHS-Lung prognostic classes (p=0.002 and p=0.008). These results confirm survival outcome benefits in patients with irAEs and suggest a higher likelihood of Grade 1-2 irAEs in patients with lower NLR or SII values or according to the NHS-Lung score.


Distinctive clinical presentation of a NF-1 patient with loss of heterozygosity of PTCH in his epithelial tumors.
Although patients with neurofibromatosis (NF) have an increased incidence of tumors, there is only one study that suggests that NF1 patients may have an increased risk for epithelial malignancies. We present a patient with known NF1 who had developed multiple epithelial tumors since early in his life. All but one of these tumors were morphologically most consistent with trichoepitheliomas. Loss of heterozygosity (LOH) for Patched 1 gene (PTCH) was demonstrated within two of the trichoepitheloma-like tumors and one tumor diagnosed as basal cell carcinoma, and the patient was show to have a PTCH gene deletion. To our knowledge, a patient presenting with both NF1 and multiple trichoepitheliomas (MTE) has not previously been reported. The dysregulation in cellular proliferation and signaling induced by decreased NF1 along with the PTCH gene mutation may explain the pattern of immunohistochemical staining within these tumors, and the rare association of NF1 with epithelial neoplasms.


Interleukin-18, CRP and procalcitonin levels in vesicoureteral reflux and reflux nephropathy.
Some patients with vesicoureteral reflux (VUR) develop reflux nephropathy (RN) and a number of them progress to chronic kidney disease (CKD). However, it is unclear to predict which patient will develop RN and/or CKD. The aim of this study is to evaluate the role of Interleukin-18 (IL-18), C-reactive protein (CRP) and procalcitonin (PCT) as an indicator of RN in VUR. Ninety-three children aged 3.5-16 years with primary VUR were enrolled. Patients were divided into two groups according to the presence of renal scarring (RS). CRP, PCT, blood urea nitrogen (BUN), serum creatinine (Scr), urinary protein (Up), creatinine (Ucr) and microalbumin (Umalb), serum and urine IL-18 levels were determined during urinary tract infection (UTI) free episode. BUN, Scr, Up/Ucr and Umalb/Ucr concentrations were higher whereas calculated creatinine clearance (Ccr) values were lower in RS (+) group compared to RS (-) group. CRP, PCT, serum and urine IL-18 levels and mean urine IL-18/Cr concentrations were similar in both groups. Serum and urine IL-18 levels did not differ according to the grade of VUR. No significant correlation was found between CRP, PCT and IL-18. Proteinuria and microalbuminuria are valuable hallmarks of RN. CRP and PCT seem not to be reliable indicators of RN in VUR patients. Moreover, serum and urine IL-18 might not predict RN.


Mode of action of human beta-defensin 3 against Staphylococcus aureus and transcriptional analysis of responses to defensin challenge.
Human beta-defensin 3 (hBD3) is a highly charged (+11) cationic defence peptide, which retains activity against staphylococci even at elevated salt concentrations. We studied the antibiotic mode of action of hBD3 against Staphylococcus aureus SG511, using whole-cell assays and analysing the transcriptional response to hBD3 treatment. hBD3 caused rapid killing and simultaneously blocked all biosynthetic pathways, however, significant depolarisation was not observed and permeabilisation of the membrane was incomplete. The transcriptional response pattern was in part similar to those of strongly cationic amphiphiles, e.g. in that anaerobic energy production was downregulated. Significantly, part of the staphylococcal cell wall stress stimulon were upregulated. The most prominent microbial counterstrategy appears to be based on the upregulation of ABC transporters possibly functioning in detoxification of the membrane environment; the transporter genes were highly upregulated in both, a short-term response and a long-term adaptation experiment. Knockout of the most highly induced transporter VraDE significantly enhanced hBD3 susceptibility. We propose that the antibiotic activity of hBD3 is based on interference with the organisation over space and time of membrane-bound multienzyme machineries such as the electron transport chain and, in particular, the cell wall biosynthesis complex rather than on formation of defined transmembrane pores.


Development of odor-guided behavior in Wistar and Sprague-Dawley rat pups.
The odor of home-cage shavings attracts Sprague-Dawley and Wistar pups 3-4 days old. Attraction increases during postnatal week one in both strains. Lemon odor repels Sprague-Dawley pups 3 and 8 days old equally, while Wistar aversion to lemon increases during the first postnatal week. Shavings from the nests of strange litters 4 or 8 days old attract Sprague-Dawley pups 4 but not 8 days old equally. Sensory changes appear to underlie Sprague-Dawley response development, while locomotor and sensory changes may mediate Wistar response ontogeny.


Vitamin D levels are not associated with ovarian reserve in a group of infertile women with a high prevalance of diminished ovarian reserve.
To determine whether a relationship exists between vitamin D (25OH-D) levels and ovarian reserve parameters (antimüllerian hormone [AMH] and FSH levels) in a large cohort of infertile women with a high prevalence of diminished ovarian reserve. Retrospective cohort study. Academically affiliated private fertility center. A total of 457 infertile women 21-50 years of age who had baseline hormone measurements. None. Statistical analyses to determine whether a relationship exists between AMH, FSH, and serum 25OH-D levels. As defined by 25OH-D <20.0 ng/mL, 74/457 patients (16.2%) had vitamin D deficiency. AMH and FSH levels did not vary between women with vitamin D deficiency and those with normal levels (0.8 ± 3.0 vs. 0.5 ± 1.6 ng/mL [P=.18] and 9.4 ± 7.2 vs. 9.2 ± 9.5 mIU/mL [P=.54], respectively). Multivariate linear regression analysis of log-transformed AMH and FSH with 25OH-D levels adjusted for age, body mass index, and seasonal variation confirmed lack of association. Receiver operating characteristic (ROC) analysis to determine if 25OH-D levels are predictive of AMH showed areas under the ROC curves (AUCs) for women <38 years of age to be 0.501, 0.554, and 0.511 for AMH threshold values of 0.5 ng/mL, 1.0 ng/mL, and 5.0 ng/mL, respectively. For women ≥38 years respective AUC values were 0.549, 0.545, and 0.557 ng/mL. Vitamin D levels were not associated with ovarian reserve in a large group of infertile women with a high prevalence of diminished ovarian reserve. Previously reported vitamin D-associated outcomes in infertility patients may, therefore, be mediated by factors other than ovarian reserve.


Purification, properties and glycoprotein nature of arylsulfatase A from sheep brain.
A simple and rapid method for the purification of arylsulfatase A (EC 220.127.116.11) from sheep brain has been developed. This includes the concanavalin A-Sepharose affinity chromatography and the pH-dependent polymerization and depolymerization of the enzyme. By these methods a homogeneous enzyme was obtained and the enzyme was purified 7180-fold. Sheep brain arylsulfatase A has been shown to be a glycoprotein containing 25% neutral sugar and 0.5% sialic acid. The constituent neutral sugars were identified as glucose and mannose.


PGE(2) induces MUC2 and MUC5AC expression in human intrahepatic biliary epithelial cells via EP4/p38MAPK activation.
MUC2 and MUC5AC overproduction is considered to be associated with hepatolithiasis and related to inflammation. However, mechanisms underlying MUC upregulation under inflammatory stimulation in human intrahepatic biliary epithelial cells (HIBECs) are not completely understood. Expression of MUC2 and MUC5AC mRNA in HIBECs was detected by real-time PCR. Expression of COX-2, EP4, and phosphorylated ERK, JNK and p38MAPK protein was detected by Western blot. Concentrations of PGE2, IL-1β and TNF-α in cell culture supernatants were measured using the Quantikine Elisa kit. COX-2 expression as well as PGE2 production in HIBECs was upregulated significantly by LPS, which was completely blocked by either TLR4 antagonist or NFκB inhibitor. Selective COX-2 inhibitor suppressed LPS-induced MUC2 and MUC5AC mRNA expression remarkably. Exogenous PGE2 increased MUC2 and MUC5AC mRNA expression in a dosage-dependent manner independent of IL-1β and TNF-α. PGE2 receptor EP4 agonist elevated MUC2 and MUC5AC expression, whereas EP4 antagonist had the opposite effect. Expression of phosphorylated p38MAPK was upregulated by exogenous PGE2, and p38MAPK inhibitor reduced MUC2 and MUC5AC expression in HIBECs. In addition, it was found that levels of PGE2, MUC2 and MUC5AC in bile samples from the hepatic ducts affected by intrahepatic stones were significantly higher than those from the unaffected hepatic ducts of patients with hepatolithiasis. Our findings indicate that PGE2 induces MUC2 and MUC5AC expression in HIBECs via EP4-p38MAPK signaling.


Predator-mediated apparent competition between two herbivores that feed on grapevines.
We have been releasing economically unimportant herbivorous mites of one species early in the season and protecting grapevines against another, more damaging herbivorous mite throughout the growing season. In this experiment, releases of economically unimportant Willamette mites alone, or of predatory mites alone, failed to reduce populations of the damaging Pacific spider mite. However, where both herbivorous Willamette mites and predatory mites were released together populations of Pacific mites were reduced. This interaction between effects of Willamette mites and predatory mites suggests that predation against Pacific mites was more effective where alternate prey (Willamette mites) were available for the predators. The "apparent competition" between Willamette mites and Pacific mites, mediated through their shared predator, can be an important force in the agroecosystem although its importance varies from year to year and vineyard to vineyard.


Effects of photoperiod on pituitary levels of three forms of GnRH and reproductive hormones in the male European sea bass (Dicentrarchus labrax, L.) during testicular differentiation and first testicular recrudescence.
Photoperiod is one of the main external cues in the control of different stages of fish development. In the present work, the effect of several photoperiods, known to delay spawning in adult fish, was investigated in juvenile male sea bass (Dicentrarchus labrax) during testicular differentiation and first testicular recrudescence. Fish were exposed to constant long (LO), expanded (EX), constant short photoperiod with long photoperiod in October (SLoct) and constant short photoperiod with long photoperiod in December (SLdec) during two consecutive years. Pituitary levels of three forms of gonadotropin-releasing hormone (GnRH) [sea bream GnRH (sbGnRH), chicken GnRH-II (cGnRH-II), and salmon GnRH (sGnRH)] were analysed and plasma levels of gonadotropin (LH), testosterone (T), and 11-ketotestosterone (11-KT) were determined in the same periods. During both periods, pituitary levels of sbGnRH were higher than cGnRH-II and sGnRH in all groups. The three GnRHs had significantly lower values in November 1995 in groups exposed to artificial photoperiods during the testicular differentiation and growth period compared to the control group. In addition, a significant effect of LO, EX, and SLoct photoperiods was observed in the LH plasma profile, showing a significant delay in the peak of LH compared to the control group. However, no significant effect of the artificial photoperiods on the pituitary content of the three GnRHs has been observed during the first testicular recrudescence. Deeper studies are needed to understand the effect of artificial photoperiods on the endocrine events occurring during both histological testicular differentiation and growth and first testicular maturation in the sea bass.


The role of a new polyclonal competitive thyroglobulin assay in the follow-up of patients with differentiated thyroid cancer with structural disease but low levels of serum thyroglobulin by immunometric and LC-MS/MS methods.
The aims of this study were to assess the role of an in-house competitive thyroglobulin assay (Tg-c) in the follow-up of metastatic differentiated thyroid carcinoma (DTC) patients who presented underestimated Tg measurements by immunometric assays (Tg-IMA) and to compare the results with IMA and LC-MS/MS Tg methods. This prospective study included 40 patients. Twenty-one with metastatic disease: 14 had Tg-IMA levels inappropriately low or undetectable (eight patients with positive and six with borderline TgAb) and seven had high Tg-IMA levels. Nineteen had an excellent response to therapy. The competitive assay employs a polyclonal antibody produced in rabbits immunized with human Tg, Tg labeled with biotin, and for the solid phase separation, a monoclonal anti-rabbit IgG antibody adsorbed to microtiter plates. All 14 patients with structural disease and underestimated levels of Tg-IMA presented detectable Tg-c levels. The median Tg-c level in the group with positive TgAb was 183 µg/L (range: 22-710 µg/L), and 58 µg/L (range 23-148 µg/L) in the borderline TgAb group. The levels of Tg-LC-MS/MS were detectable in some patients (range < 0.5-18 µg/L). All seven patients with high Tg-IMA presented also high levels of Tg-c. Only 2/19 patients with excellent response had Tg-c levels above the functional sensitivity. The competitive assay was able to detect Tg in all patients, even in the presence of serum TgAb, and may be an option in patients with underestimated Tg-IMA and relevant structural disease.


The development of a radioimmunoassay for cannabinoids in blood and urine.
Antibodies, for use in radioimmunoassay, have been raised in sheep by immunization with a conjugate of delta9-tetrahydrocannabinol hemisuccinate and bovine serum albumin. Antiserum titre and avidity were increased by successive booster doses of conjugate. The high degree of non-specific binding encountered in the radioimmunoassay of cannabinoids was reduced by the use of the solubilizing detergent Triton X-405 and by restricting protein concentration in the assay medium. Plasma samples were deproteinized with ethanol before assay, but urine was directly assayed. High avidity antibodies and high specific activity [3H]-delta9-tetrahydrocannabinol permitted the detection of 50 pg of cross-reacting cannabinoids--a sensitivity of 7-5 ng ml-1 of plasma and 1-0 ng ml-1 of urine. Whilst apparently specific for the three-ringed cannabinoid nucleus, the assay antiserum cross-reacted with several cannabinoids, both natural compounds and metabolites. Partial identification of cross-reacting cannabinoids was achieved by the use of pure compounds and by the assay of plasma and urine samples collected from rabbits given pure cannabinoids intravenously.


Do folic acid supplements reduce facial clefts?
This was a national population-based case-control study in Norway. CASE AND CONTROL SELECTION: Cases consisted of all newborn infants born from 1996-2001 who had been referred for surgical treatment of a cleft [either cleft lip with or without cleft palate (377 children) or cleft palate only (196 children)]. Controls (763) were a randomly selected at an average of four per 1000 live births (identified through the medical birth registry of Norway). Data were collected using questionnaires. Crude odds ratios (OR) were calculated and adjustments for potential confounders (diet and multivitamins, mother's education, mother's employment during early pregnancy, smoking, alcohol consumption, and year of baby's birth) were made. Folic acid supplementation during early pregnancy (400 microg/day) was associated with a reduced risk of isolated cleft lip with or without cleft palate after adjustment for multivitamins, smoking, and other potential confounding factors [adjusted OR, 0.61; 95% confidence interval (CI), 0.39-0.96]. Independent of supplements, diets rich in fruits, vegetables and other high-folate-containing foods reduced the risk somewhat (adjusted OR, 0.75; 95% CI, 0.50-1.11). The lowest risk of cleft lip was among women who ate folate-rich diets who also took folic acid supplements and multivitamins (adjusted OR, 0.36; 95% CI, 0.17-0.77). Folic acid provided no protection against cleft palate alone (adjusted OR, 1.07; 95% CI, 0.56-2.03). Folic acid supplements during early pregnancy seem to reduce the risk of isolated cleft lip (with or without cleft palate) by about a third. Other vitamins and dietary factors may provide additional benefit.


Intratumoral hemorrhage because of primary spinal mixed germ cell tumor presenting with atypical radiological features in an adult.
Germ cell tumors are known to arise in the central nervous system, usually in the intracranial regions. However, primary spinal mixed germ cell tumors are extremely rare. This is the first reported case of intratumoral hemorrhage because of a primary spinal mixed germ cell tumor consisting of germinoma and immature teratoma in the conus medullaris of an adult patient that presented with rapid changes on magnetic resonance image (MRI). We report this rare case and discuss the clinical manifestations of an intramedullary spinal mixed germ cell tumor in adult. A case report. A 42-year-old woman experienced buttock numbness, and a spinal cord tumor was observed on the conus medullaris on MRI. The patient was scheduled for an operation in 1 month, but she developed sudden-onset neurologic deterioration. Rapid progression of the tumor was observed on follow-up MRI. The tumor was removed by emergency surgery and was identified as a primary mixed germinoma and immature teratoma. The patient received adjuvant chemotherapy and radiotherapy after gross total resection. The neurologic deficit of the patient was relieved, and recurrence of the tumor was not observed 26 months after the surgery. We present this rare case and emphasize the necessity of precise diagnosis and early treatment of primary spinal germ cell tumor. Close observation on MRI is required after surgery, and adjuvant chemotherapy and radiotherapy should be considered according to the pathologic features.


Calcium sensing receptor activation in THP-1 macrophages triggers NLRP3 inflammasome and human preadipose cell inflammation.
Excess adipose tissue (AT) associates with inflammation and obesity-related diseases. We studied whether calcium-sensing receptor (CaSR)-mediated NLRP3 inflammasome activation in THP-1 macrophages elevates inflammation in LS14 preadipocytes, modeling deleterious AT cell crosstalk. THP-1 macrophages exposed to cinacalcet (CaSR activator, 2 μM, 4 h) showed elevated proinflammatory marker and NLRP3 inflammasome mRNA, pro-IL-1β protein and caspase-1 activity, whereas preincubation with CaSR negative modulators prevented these effects. The key NLRP3 inflammasome component ASC was silenced (siRNA) in THP-1 cells, and inflammasome activation was evaluated (qPCR, Western blot, caspase-1 activity) or they were further cultured to obtain conditioned medium (CoM). Exposure of LS14 preadipocytes to CoM from cinacalcet-treated THP-1 elevated LS14 proinflammatory cytokine expression, which was abrogated by THP-1 inflammasome silencing. Thus, CaSR activation elevates THP-1-induced inflammation in LS14 preadipocytes, via macrophage NLRP3 inflammasome activation. Modulating CaSR activation may prevent deleterious proinflammatory cell crosstalk in AT, a promising approach in obesity-related metabolic disorders.