Evaluation of changes in the upper airway after Twin Block treatment in patients with Class II malocclusion.
The purpose of this prospective case control study is to describe in growing patients with mandibular hypoplasia, treatment outcomes following functional therapy in terms of volumetric changes in nasopharynx and oropharynx, that is, upper and lower pharynx. We recruited 60 study participants aged between 8 and 12 years having mandibular Class II malocclusion and a reduced upper airway (UA) size, as determined by McNamara cephalometric analyses. Forty patients received Twin Block treatment, whereas the remaining 20 patients did not receive treatment, thus constituting the control group. The control group included patients who did not start treatment after their first visit but returned for a consultation one or 2 years later. All patients underwent an initial teleradiography examination of the skull and a final teleradiography examination to measure changes using McNamara cephalometric analysis of the UA. Pretreatment and posttreatment changes were assessed using Student's t test for independent samples with a significance level of 0.05. Both anatomical structures analyzed-the upper pharynx (nasopharynx) and lower pharynx (oropharynx)-showed significant increases after treatment regardless of whether the patients were boys or girls. The controls showed a decrease in UA size on average after approximately 2 years of growth. A clear relationship exists between the mandibular advancement achieved with TB treatment and an increased UA size. Therefore, the appliance is considered suitable for improving the respiratory quality of growing patients with a decreased UA size.


Circumvaginal surface electromyography in women with urinary incontinence and in healthy volunteers.
In this study we developed a probe for surface EMG investigation of the circumvaginal muscle function in women with various forms of urinary incontinence. 69 women were investigated, 20 healthy volunteers, 25 patients with stress incontinence, 11 with urge incontinence and 13 with a mixed type of incontinence. We found that the circumvaginal surface EMG activity at short lasting (2 sec) maximum contraction was significant lower in patients with incontinence compared to healthy volunteers. We also found that the ability to hold a maximum contraction during one minute was significant reduced in all the patient groups compared to controls. The results suggest that patients with stress, urge or mixed incontinence all seem to have a defective function of the circumvaginal musculature. A common aetiology for stress, urge and mixed incontinence seems to be a reasonable working hypothesis for future investigations.


Dietary inflammatory index and its association with renal function and progression of chronic kidney disease.
While evidence exists for an association between the dietary inflammatory index (DII) and cardiovascular diseases, the relation between DII and chronic kidney disease (CKD) is not known. To examine the association between DII, renal function and progression of CKD. In this cross-sectional study, dietary data from 221 subjects with diagnosed CKD were collected using a validated food frequency questionnaire. DII was calculated based on overall inflammatory effect scores. Renal function was measured by blood urea nitrogen (BUN) and serum creatinine (Cr) level as well as estimated glomerular filtration rate (eGFR). Patients in the first tertile of DII consumed higher quantities of vegetables, fruits, dairy, calcium, potassium and phosphorus and lower amounts of grains (P < 0.01 for all). We did not detect any significant trend for BUN, Cr and eGFR across tertiles of DII in crude and two adjusted models. In a fully adjusted model, an increased risk of being in the higher stage of CKD was found among those in the top tertiles of DII (odds ratio: 2.12; 95% CI: 1.05, 4.26; P for trend = 0.03). We observed that compliance with a pro-inflammatory diet in patients with CKD may be associated with disease progression.


Antioxidative activity of barley hordein and its loss by deamidation.
Barley hordein was comparable to maize zein in antioxidation under a powder model system. Various deamidated "hordein" preparations were obtained and examined for their molecular-size distribution (by Sephacryl S-100 gel filtration), hydrophobicity (by fluorescence measurement using fluorescent probes) and antioxidative activity (by the ferric thiocyanate method). Deamidation caused fragmentation of the hordein molecule and simultaneously lowered its fatty acid-binding capacity rather than its surface hydrophobicity. Then, the antioxidative activity diminished with increasing deamidation. When the fatty acid-binding capacity was plotted against the antioxidative activity, a high correlation (r2 = 0.92) was observed between these two events.


Role of oxidative stress in experimental sepsis and multisystem organ dysfunction.
Massive increase in radical species can lead to oxidative stress, promoting cell injury and death. This review focuses on experimental evidence of oxidative stress in critical illnesses, sepsis and multisystem organ dysfunction. Oxidative stress could negatively affect organ injury and thus overall survival of experimental models. Based on this experimental evidence, we could improve the rationale of supplementation of antioxidants alone or in combination with standard therapies aimed to reduce oxidative stress as novel adjunct treatment in critical care.


Genetic diagnosis of human embryos.
For all the worried talk about genetic engineering over the last two decades, it is surprising how quietly plans for the genetic diagnosis of human embryos have developed. The issues raised warrant careful examination: what needs are met through embryo diagnosis? Who bears responsibility for monitoring this technique? Under what overarching ethic should embryo diagnosis and, eventually, embryo therapy, be applied? What are the broader social implications raised by the genetic diagnosis of human embryos?


Dopamine and serotonin mediate the impact of stress on cleaner fish cooperative behavior.
Stress is known to modulate behavioral responses and rapid decision-making processes, especially under challenging contexts which often occur in social and cooperative interactions. Here, we evaluated the effects of acute stress on cooperative behavior of the Indo-Pacific cleaner wrasse (Labroides dimidiatus) and the implications of pre-treatment with monoaminergic compounds: the selective serotonin reuptake inhibitor - fluoxetine, the 5-HT1A receptor antagonist - WAY-100,635, the D1 receptor agonist - SKF-38393, and the D1 receptor antagonist - SCH-23390. We demonstrated that stress decreased the predisposal to interact and increased cortisol levels in cleaners, which are alleviated by fluoxetine and the dopaminergic D1 antagonist. Overall, our findings highlight the crucial influence of stress on cooperative behavior.


Gastric gastrointestinal stromal tumors: therapeutic strategies and long-term prognosis.
This study aimed to evaluate the clinical and prognostic characteristics of primary gastric gastrointestinal stromal tumors (GIST). Patients who underwent resection for primary gastric GIST between January 2002 and December 2017 were included. Recurrence-free survival (RFS) was calculated by Kaplan-Meier analysis, and Cox proportional hazards model was used to identify independent prognostic factors. Altogether, 653 patients were enrolled. The median patient age was 59 years (range 15-86 years). Open, laparoscopic, and endoscopic resections were performed in 394 (60.3%), 105 (16.1%), and 154 (23.6%) patients, respectively. According to the modified NIH consensus classification, 132 (20.2%), 245 (37.5%), 166 (25.4%), and 88 (13.5%) patients were categorized into very low-, low-, intermediate-, and high-risk, respectively. A total of 136 (20.8%) patients received adjuvant imatinib treatment. The median follow-up time was 78 months (range 4-219 months), and the estimated 5-year RFS rate was 93.0%. In all patients, tumor size and rupture, mitotic counts, and adjuvant imatinib treatment were independent prognostic factors. The prognosis of gastric GIST treated with endoscopic resection was not significantly different from that of laparoscopic or open resection after adjusting for covariates using propensity score matching (log-rank p = .558). Adjuvant imatinib treatment (HR = 0.151, 95%CI 0.055-0.417, p < .001) was a favorable prognostic factor for high-risk patients, but was not associated with prognosis in intermediate-risk patients. Patients with small gastric GISTs who successfully underwent endoscopic resection may have a favorable prognosis. Adjuvant imatinib treatment improve the prognosis of high-risk gastric GISTs, however, its use in intermediate-risk patients remains controversial.


Analysis of stable oxidized molecular species of glycerophospholipids following treatment of red blood cell ghosts with t-butylhydroperoxide.
A model of lipid peroxidation was employed to investigate the formation of oxidized phospholipids in red blood cell membranes after treatment with t-butylhydroperoxide (tBuOOH). On-line normal-phase HPLC/mass spectrometry (LC/MS) with electrospray ionization was used to separate phospholipid classes and analyze the distribution of the major poly-unsaturated fatty acyl groups and corresponding oxidation products. Arachidonic acid was observed primarily in plasmalogen glycerophosphoethanolamine (GPE), whereas linoleic acid was equally distributed in 1,2-diacyl-GPE and glycero-phosphocholine (GPC) lipids. The additions of one and two oxygen atoms to poly-unsaturated phospholipid molecular species were observed as the major, stable products after incubation with tBuOOH. Tandem mass spectrometry was utilized to further structurally characterize the oxidized fatty acyl groups which were identified as 5-, 8-, 9-, 11-, 12-, and 15-hydroxy-eicosatetraenoate (HETE) and 5-, 12-, and 15-hydroperoxyeicosatetraenoate (HpETE) in addition to 9- and 13-hydroxyoctadecadienoate (HODE) and 9- and 13-hydroperoxyoctadecadienoate (HpODE). Although 18:0p/20:4-GPE was the predominate phospholipid species containing arachidonic acid, the major species containing HETE and HpETE were the 1,2-diacyl-GPE with hexadecanoate as the sn-1 substituent. This result would be consistent with a differential pathway of oxidative degradation of arachidonoyl plasmalogen GPE suggesting a unique role for this plasmalogen molecular species glycerophospholipid.


Talin2 and KANK2 functionally interact to regulate microtubule dynamics, paclitaxel sensitivity and cell migration in the MDA-MB-435S melanoma cell line.
Focal adhesions (FAs) are integrin-containing, multi-protein structures that link intracellular actin to the extracellular matrix and trigger multiple signaling pathways that control cell proliferation, differentiation, survival and motility. Microtubules (MTs) are stabilized in the vicinity of FAs through interaction with the components of the cortical microtubule stabilizing complex (CMSC). KANK (KN motif and ankyrin repeat domains) family proteins within the CMSC, KANK1 or KANK2, bind talin within FAs and thus mediate actin-MT crosstalk. We previously identified in MDA-MB-435S cells, which preferentially use integrin αVβ5 for adhesion, KANK2 as a key molecule enabling the actin-MT crosstalk. KANK2 knockdown also resulted in increased sensitivity to MT poisons, paclitaxel (PTX) and vincristine and reduced migration. Here, we aimed to analyze whether KANK1 has a similar role and to distinguish which talin isoform binds KANK2. The cell model consisted of human melanoma cell line MDA-MB-435S and stably transfected clone with decreased expression of integrin αV (3αV). For transient knockdown of talin1, talin2, KANK1 or KANK2 we used gene-specific siRNAs transfection. Using previously standardized protocol we isolated integrin adhesion complexes. SDS-PAGE and Western blot was used for protein expression analysis. The immunofluorescence analysis and live cell imaging was done using confocal microscopy. Cell migration was analyzed with Transwell Cell Culture Inserts. Statistical analysis using GraphPad Software consisted of either one-way analysis of variance (ANOVA), unpaired Student's t-test or two-way ANOVA analysis. We show that KANK1 is not a part of the CMSC associated with integrin αVβ5 FAs and its knockdown did not affect the velocity of MT growth or cell sensitivity to PTX. The talin2 knockdown mimicked KANK2 knockdown i.e. led to the perturbation of actin-MT crosstalk, which is indicated by the increased velocity of MT growth and increased sensitivity to PTX and also reduced migration. We conclude that KANK2 functionally interacts with talin2 and that the mechanism of increased sensitivity to PTX involves changes in microtubule dynamics. These data elucidate a cell-type-specific role of talin2 and KANK2 isoforms and we propose that talin2 and KANK2 are therefore potential therapeutic targets for improved cancer therapy.


Methylation status of a single CpG locus 3 bases upstream of TATA-box of receptor activator of nuclear factor-kappaB ligand (RANKL) gene promoter modulates cell- and tissue-specific RANKL expression and osteoclastogenesis.
Receptor activator of nuclear factor-kappaB ligand (RANKL) expression is tissue specific and limited to certain subsets of T-lymphocytes and stromal/osteoblastic cells. Even among osteoblasts, RANKL is expressed on about 20% of osteoblasts of the normal mouse. To clarify the mechanism of population-specific RANKL expression, we analyzed the effect of CpG methylation on its transcription, mRNA and protein expression as well as on osteoclastogenesis. Subpopulations of ST2 cells were used: P9, which expresses RANKL and supports osteoclastogenesis, and P16, which does not. By sodium bisulfite mapping, the rate of CpG methylation of the -65/+350 region, especially of CpG locus no. 1 three bases upstream of the TATA-box, was higher in P16 than in P9 ST2 cells. ChIP and gel shift assay showed that methylated CpG locus no. 1 was a target of MeCP2 binding that, in turn, blocked the binding of the TATA-box binding protein to the TATA-box. In vitro methylation by SssI of the promoter construct reduced its transcriptional activity at the steady state and its response to 1alpha,25(OH)2 vitamin D3. Conversely, treatment with DNA methylase inhibitor, 5-aza-2'-deoxycytidine, significantly restored RANKL expression and osteoclastogenesis in P16 cells. Except for primary cultured osteoblasts, CpG locus no. 1 was frequently methylated in various normal mouse tissues. We propose that the methylation status of the CpG locus three bases upstream of the TATA-box modulates the control of cell- and tissue-specific expression of RANKL gene and osteoclastogenesis. The heterogeneity of stromal/ osteoblastic cells in response to bone-resorbing stimuli may be attributed, in part, to the methylation status of the RANKL gene promoter.


Measuring nurses' computer competency: an analysis of published instruments.
The rapid expansion of computer-driven technologies into multiple aspects of modern healthcare suggests that many of the important competencies of the 21st century nurse will encompass mastery of computer technology. This is a comprehensive review of the published measures of computer competence during the past 12 years. Essential knowledge, attitudes, and skills were identified and classified. Multiple competency assessment instruments of varying quality were examined. Little agreement was found regarding specific computer-focused competencies necessary for nurses. Taken as a whole, however, there is consensus that the computer-competent nurse possesses a general knowledge and understanding of computer technology, coupled with a positive attitude toward computers and software. In addition, such a nurse is skillful in computer hardware and software use and able to grasp how such technology benefits nursing and the overall healthcare environment.


Microdialysis: the Key to Physiologically Based Model Prediction of Human CNS Target Site Concentrations.
Despite the enormous research efforts that have been put into the development of central nervous system (CNS) drugs, the success rate in this area is still disappointing. To increase the successful rate in the clinical trials, first the problem of predicting human CNS drug distribution should be solved. As it is the unbound drug that equilibrates over membranes and is able to interact with targets, especially knowledge on unbound extracellular drug concentration-time profiles in different CNS compartments is important. The only technique able to provide such information in vivo is microdialysis. Also, obtaining CNS drug distribution data from human subjects is highly limited, and therefore, we have to rely on preclinical approaches combined with physiologically based pharmacokinetic (PBPK) modeling, taking unbound drug CNS concentrations into account. The next step is then to link local CNS pharmacokinetics to target interaction kinetics and CNS drug effects. In this review, system properties and small-molecule drug properties that together govern CNS drug distribution are summarized. Furthermore, the currently available approaches on prediction of CNS pharmacokinetics are discussed, including in vitro, in vivo, ex vivo, and in silico approaches, with special focus on the powerful combination of in vivo microdialysis and PBPK modeling. Also, sources of variability on drug kinetics in the CNS are discussed. Finally, remaining gaps and challenges are highlighted and future directions are suggested.


BOLD correlates of continuously fluctuating epileptic activity isolated by independent component analysis.
Combined EEG/fMRI recordings offer a promising opportunity to detect brain areas with altered BOLD signal during interictal epileptic discharges (IEDs). These areas are likely to represent the irritative zone, which is itself a reflection of the epileptogenic zone. This paper reports on the imaging findings using independent component analysis (ICA) to continuously quantify epileptiform activity in simultaneously acquired EEG and fMRI. Using ICA derived factors coding for the epileptic activity takes into account that epileptic activity is continuously fluctuating with each spike differing in amplitude, duration and maybe topography, including subthreshold epileptic activity besides clear IEDs and may thus increase the sensitivity and statistical power of combined EEG/fMRI in epilepsy. Twenty patients with different types of focal and generalized epilepsy syndromes were investigated. ICA separated epileptiform activity from normal physiological brain activity and artifacts. In 16/20 patients, BOLD correlates of epileptic activity matched the EEG sources, the clinical semiology, and, if present, the structural lesions. In clinically equivocal cases, the BOLD correlates aided to attribute proper diagnosis of the underlying epilepsy syndrome. Furthermore, in one patient with temporal lobe epilepsy, BOLD correlates of rhythmic delta activity could be employed to delineate the affected hippocampus. Compared to BOLD correlates of manually identified IEDs, the sensitivity was improved from 50% (10/20) to 80%. The ICA EEG/fMRI approach is a safe, non-invasive and easily applicable technique, which can be used to identify regions with altered hemodynamic effects related to IEDs as well as intermittent rhythmic discharges in different types of epilepsy.


Mycobacterium bovis: From Genotyping to Genome Sequencing.
Mycobacterium bovis is the main pathogen of bovine, zoonotic, and wildlife tuberculosis. Despite the existence of programs for bovine tuberculosis (bTB) control in many regions, the disease remains a challenge for the veterinary and public health sectors, especially in developing countries and in high-income nations with wildlife reservoirs. Current bTB control programs are mostly based on test-and-slaughter, movement restrictions, and post-mortem inspection measures. In certain settings, contact tracing and surveillance has benefited from M. bovis genotyping techniques. More recently, whole-genome sequencing (WGS) has become the preferential technique to inform outbreak response through contact tracing and source identification for many infectious diseases. As the cost per genome decreases, the application of WGS to bTB control programs is inevitable moving forward. However, there are technical challenges in data analyses and interpretation that hinder the implementation of M. bovis WGS as a molecular epidemiology tool. Therefore, the aim of this review is to describe M. bovis genotyping techniques and discuss current standards and challenges of the use of M. bovis WGS for transmission investigation, surveillance, and global lineages distribution. We compiled a series of associated research gaps to be explored with the ultimate goal of implementing M. bovis WGS in a standardized manner in bTB control programs.


Is there an effect of thyroid autoimmunity on the outcomes of assisted reproduction?
We aimed to evaluate the role of thyroid autoantibodies (TAA) on the outcomes of intracytoplasmic sperm injection-embryo transfer (ICSI-ET). A prospective case-control study was conducted in the in vitro fertilisation (IVF) centre of Suleymaniye Maternity Training and Research Hospital, Istanbul, Turkey between July 2013 and March 2014. A total of 49 (19.52%) TAA-positive and 202 TAA-negative patients were enrolled. Demographic characteristics and laboratory parameters were recorded. All patients underwent ICSI-ET. Thirty-one TAA-positive patients (32 cycles) and 121 TAA-negative patients (126 cycles) completed the study. Mean female age, body mass index (BMI), type of infertility, duration of infertility, antral follicle count (AFC), anti-Müllerian hormone (AMH), basal follicle stimulating hormone (bFSH), luteinising hormone (bLH), and oestradiol (bE2), prolactin and thyroid hormone profiles, male age and aetiology of infertility of both groups were similar (p > 0.05). There was no significant difference between groups in terms of duration and dose of gonadotropin (Gn) therapy, day of human chorionic Gn (hCG) administration, serum E2 and progesterone levels, number of collected oocytes, ratio of fertilisation, number of available embryos, positive pregnancy test, biochemical pregnancy, clinical pregnancy, ratio of miscarriage and ongoing pregnancy (p > 0.05). In conclusion, we failed to demonstrate a significant role of TAA on the outcomes of ICSI-ET in euthyroid patients. Further studies with larger numbers of participants are required to clarify these data.


Prevalence of atopy in an inner-city asthmatic population.
Seventy-three patients at The Mount Sinai Hospital Emergency Room were investigated to determine the prevalence of atopy in asthma in a predominantly black and Hispanic inner-city population. Serum IgE levels and radioallergosorbent tests (RASTs) to eight common inhalant allergens were measured in both the asthmatic group and a nonasthmatic emergency-room control group. The mean total IgE level for the asthma group was 263.8 IU/mL compared to 63.8 IU/mL in the control group (p = 0.032), and 60% of the asthmatics had IgE levels in the atopic range (> 100 IU/mL). Increases in IgE were associated with age under 50 years but did not reach statistical significance. Cockroach, dust mite, cat, and dog were the most common RASTs in the asthmatic group; there were no positive RASTs in the control group. There was a correlation (p = 0.04) between age (less than 50 years) and increased numbers of positive RASTs. These results are similar to those of other studies that have associated atopy with asthma in rural and suburban populations. These data demonstrate that atopy is common in the asthmatic patients seen in The Mount Sinai Hospital Emergency Room and strongly suggest that management of atopic factors should become routine in the care of adult asthmatic patients.


Total Syntheses and Anti-inflammatory Evaluations of Pongamosides A-C, Natural Furanoflavonoid Glucosides from Fruit of Pongamia pinnata (L.) Pierre.
The syntheses of three natural furanoflavonoid glucosides, including two flavone glucosides, pongamosides A (1) and B (2), and a flavonol glucoside, pongamoside C (3), were achieved for the first time in 9-15 steps from commercially available materials in overall yields ranging from 2.9% to 29%. The synthetic sequence featured a NaH-promoted BK-VK rearrangement and acid-catalyzed intramolecular cyclization to furnish the furanoflavonoid aglycone. Meanwhile, phase-transfer-catalyzed glycosylation and Schmidt's trichloroacetimidate procedure were employed to establish the pivotal O-glycosidic linkage. The anti-inflammatory activities of compounds 1-3, as well as their aglycones 5a, 5b, and 23, were determined against NO production in the LPS-stimulated RAW264.7 cells. The results indicated that the O-glycosylation may reduce the anti-inflammatory activity of furanoflavonoid in vitro.


The nutritional status of women in the first trimester of pregnancy attending an inner-city antenatal department in the UK.
We have previously found high rates of poor iron and folate status in women who had delivered a low birthweight baby (LBW) in an ethnically diverse inner-city area of the UK. However, little was known of the nutritional status in the local general obstetric population. We therefore investigated biochemical measures of nutritional status in the first trimester of the first pregnancy. Routine blood samples collected at the antenatal booking clinic were analysed for haemoglobin (Hb), serum ferritin, red cell folate (RCF) (n = 100) and erythrocyte transketolase activation coefficient (ETKAC) for thiamin status (n = 90). We found 9% of women in our sample had a low Hb level, 10% had a low serum ferritin and only one had a low RCF. This is a substantially lower number of women with biochemical deficiencies than we found previously in women three months after delivering a LBW baby. However, 34% had low thiamin status. Thiamin status was negatively correlated with gestational age at birth (r = -0.407, p < 0.001). Differences in nutritional status were observed between ethnic and socio-economic groups. Hb levels differed between ethnic (p = 0.001) and socio-economic groups (p = 0.02), with Africans and women in manual occupations/unwaged having the lowest Hb levels. RCF levels also differed between groups (p < 0.001) with Caucasians and those in non-manual occupations having highest levels. ETKAC also differed between ethnic groups (p = 0.008) with Africans having the highest level indicating a poorer status. The study highlights the need to improve nutrition particularly in ethnic minorities and low income groups who are most at risk of adverse birth outcomes such as LBW.


RNA-Seq reveals leaf cuticular wax-related genes in Welsh onion.
The waxy cuticle plays a very important role in plant resistance to various biotic and abiotic stresses and is an important characteristic of Welsh onions. Two different types of biangan Welsh onions (BG) were selected for this study: BG, a wild-type covered by wax, which forms a continuous lipid membrane on its epidermal cells, and GLBG, a glossy mutant of BG whose epidermal cells are not covered by wax. To elucidate the waxy cuticle-related gene expression changes, we used RNA-Seq to compare these two Welsh onion varieties with distinct differences in cuticular wax. The de novo assembly yielded 42,881 putative unigenes, 25.41% of which are longer than 1,000 bp. Among the high-quality unique sequences, 22,289 (52.0%) had at least one significant match to an existing gene model. A total of 798 genes, representing 1.86% of the total putative unigenes, were differentially expressed between these two Welsh onion varieties. The expression patterns of four important unigenes that are related to waxy cuticle biosynthesis were confirmed by RT-qPCR and COG class annotation, which demonstrated that these genes play an important role in defense mechanisms and lipid transport and metabolism. To our knowledge, this study is the first exploration of the Welsh onion waxy cuticle. These results may help to reveal the molecular mechanisms underlying the waxy cuticle and will be useful for waxy gene cloning, genetics and breeding as well as phylogenetic and evolutionary studies of the Welsh onion.


NATIONAL DOSE REGISTER IN FRANCE WITHIN THE NATIONAL INFORMATION SYSTEM SISERI.
Over the past decade, France has developed an electronic dose register at national level called SISERI. Institute for Radiological Protection and Nuclear Safety is in charge of the management of this information system. Besides the main purpose of being a central register of any doses measured for the individual dosimetric monitoring of all exposed workers, SISERI has been developed so as to constitute a tool for occupational physicians and radiation protection officers allowing access in real-time to the results of the individual monitoring. The SISERI information system centralises, verifies and keeps the records of all personal dosimetric results of the 370 000 workers annually monitored in France. Moreover, since the publication of a new order in 2013, employers shall declare any new workers in SISERI before the beginning of their occupation and they shall upload data concerning in particular the activity field/sector and the occupation of each worker. The enforcement of this new order is going to enrich the individual dosimetric information stored in SISERI. Thus, it is expected that more precise and accurate statistics on occupational exposure to ionising radiation in France will be established in the next few years.


Effects of ivabradine and beta-blocker therapy on dobutamine-induced ventricular arrhythmias.
Indirect evidences suggest that the If blocker ivabradine may exert an antiarrhythmic effect in ventricular myocardium in heart failure (HF) patients by inhibiting spontaneous depolarisations, but the clinical relevance of this mechanism is not known. Dobutamine (DOB) has been known to increase heart rate and the incidence of cardiac arrhythmias. In this study, we evaluated the effects of ivabradine on DOB-induced ventricular arrhythmias and compared them with those of beta-blocker (BB) therapy. Patients with decompensated HF requiring inotropic support, left ventricular ejection fraction < 35%, and in sinus rhythm were included in the study (ivabradine group - 29 patients, control group - 29 patients, BB group - 15 patients). All patients underwent Holter recording for 6 h before the initiation of DOB infusion. Following baseline recording, DOB was administered at incremental doses of 5, 10, and 15 μg/kg/min, with 6-h steps. Holter monitoring was continued during 18 h of DOB infusion and analysed for the median number of ventricular premature contractions (VPC), ventricular couplets, episodes of non-sustained ventricular tachycardia, and total ventricular arrhythmias in each step of the study protocol. The positive chronotropic effect of incremental DOB doses was blunted by beta-blockade and was totally abolished by ivabradine. The median number of VPCs, ventricular couplets, and total ventricular arrhythmias significantly increased with incremental doses of DOB in the control group (p = 0.018) and, to a lesser extent, in the ivabradine group (p = 0.015). In the BB group the absolute VPCs numbers were smaller than in the control or the ivabradine group, with the on-ivabradine VPCs numbers falling between those seen in control and BB groups. A numeric increase in VPCs with incremental DOB doses occurred in the BB group but did not reach statistical significance (p > 0.05), consistent with a protective effect of beta-blockade. Ivabradine reduced VPCs by 43% at 5 μg/kg/min DOB and by 38% at 10 μg/kg/min DOB against the control group (VPCs median 256 vs. 147 and 251 vs. 158) in the absence of significant differences at 15 μg/kg/min DOB between the control and ivabradine groups (overall p > 0.05). Thus, ivabradine administered without background beta-blockade attenuated the arrhythmogenic effect of increasing doses of DOB in the low and moderate DOB dose but not in the high DOB dose. In patients with decompensated HF, ivabradine appears to reduce the incidence of VPCs in response to low and medium DOB dose. Whether the anti-arrhythmic effect of ivabradine is additive to the anti-arrhythmic effect of beta-blockade requires further investigation; this should also determine the clinical significance of ventricular arrhythmia attenuation with ivabradine.


MnSe embedded in carbon nanofibers as advanced anode material for sodium ion batteries.
MnSe with high theoretical capacity and reversibility is considered as a promising material for the anode of sodium ion batteries. In this study, MnSe nanoparticles embedded in 1D carbon nanofibers (MnSe-NC) are successfully prepared via facile electrospinning and subsequent selenization. A carbon framework can effectively protect MnSe dispersed in it from agglomeration and can accommodate volume variation in the conversion reaction between MnSe and Na+ to guarantee cycling stability. The 1D fiber structure can increase the area of contact between electrode and electrolyte to shorten the diffusion path of Na+ and facilitate its transfer. According to the kinetic analysis, the storage process of sodium by MnSe-NC is a surface pseudocapacitive-controlled process with promising rate capability. Impressively, An MnSe-NC anode in sodium ion full cells is investigated by pairing with an Na3V2(PO4)2@rGO cathode, which exhibits a reversible capacity of 195 mA h g-1 at 0.1 A g-1.


Ectopic gallbladder with congenital biliary dilatation: a pediatric case report.
An ectopic gallbladder is a rare anomaly and can result in the misinterpretation of imaging findings and clinical confusion. Knowledge of such anomalies facilitates accurate diagnoses and prompt management. We report a pediatric case of an ectopic gallbladder concomitant with congenital biliary dilatation (CBD). A 9-year-old girl was referred to our hospital for elevated liver enzyme levels. Following physical examination and a review of medical imaging findings, she was diagnosed with Todani type IV-A CBD. We could not visualize the gallbladder by abdominal ultrasonography, CT, and MRI scans; therefore, we suspected gallbladder agenesis. A laparoscopic excision of the extrahepatic bile duct was performed to treat the CBD. Neither a gallbladder nor a cystic duct were revealed on the liver undersurface. Therefore, gallbladder agenesis was considered as a diagnosis based on preoperative imaging and intraoperative findings. However, during dissection of the hepatic hilum, a cyst-like structure was found on the ventral side of the common hepatic duct, slightly to the right, and a small additional duct that originated from the cystic structure was found. Upon incision, a small amount of bile was drained from the small duct. Thus, the cystic structure was diagnosed as an ectopic gallbladder with hypoplasia. Following the removal of the ectopic gallbladder, the extrahepatic bile duct was excised. Subsequently, laparoscopic Roux-en-Y hepaticojejunostomy was performed without any complications. Postoperative histopathological evaluations of the resected specimen revealed Rokitansky-Aschoff sinuses in the resected cystic lesion. The pathological investigations confirmed the diagnosis of an ectopic gallbladder. Following an uneventful postoperative course, the patient was discharged on day nine. To our knowledge, this is the first pediatric case report describing an ectopic gallbladder concomitant with CBD. If the gallbladder cannot be detected in a preoperative imaging examination, it is important to consider the possibility of an ectopic gallbladder.


Emerging dermatologic issues in the oncology patient.
The spectrum of skin diseases that occurs in the oncology patient differs somewhat from that seen in other immunosuppressed populations. We review the cutaneous manifestations of invasive mold infections in the leukemia/lymphoma population. Aspergillus mold infections are now the leading infectious cause of death in this population. We also review the pustular eruption caused by a new class of chemotherapy for solid malignancies. An update on cutaneous graft-versus-host disease appears elsewhere in this journal. Cutaneous squamous cell carcinomas and basal cell carcinomas occur more frequently in the chronic lymphocytic leukemia and non-Hodgkin's lymphoma population; this is discussed, as is the more aggressive clinical course of these tumors.


Lipid Nutrition and the Epidermal Barrier: The Connection Between Immune-Mediated Inflammatory Diseases and Peroxisome Proliferator-Activated Receptors, a New Therapeutic Target in Psoriasis and Atopic Dermatitis.
The authors describe peroxisome proliferator-activated receptor (PPAR) transcription factors as connectors between the enzymatic mechanisms of the epidermal barrier and the abnormal immune and inflammatory responses that characterize atopic dermatitis and psoriasis. Also described is a new connection between lipid metabolism and the epidermal barrier. A suggestion that emerges is that atopic dermatitis and psoriasis share at least 2 pathogenic mechanisms-namely, deficient expression of PPAR-#a and impaired production of interleukin-10 and interferon-γ-in spite of differences in causes and manifestations. A standardized olive oil formulation with powerful bactericidal and fungicidal effects also has the ability to increase serum levels of these 2 cytokines and regulate serum levels of high-density lipoprotein cholesterol in patients at high risk for inflammatory and cardiovascular disease, suggesting that these may be among the mechanisms responsible for the benefits observed following oral and/or topical administration in patients with atopic dermatitis or psoriasis.


Predominant immunoreactivity of Porphyromonas gingivalis heat shock protein in autoimmune diseases.
Autoimmune diseases, including atherosclerosis, diabetes mellitus and rheumatoid arthritis, can be triggered and aggravated by the pathogen-driven antigenic peptide from Porphyromonas gingivalis HSP60. P. gingivalis is the major pathogen of chronic periodontitis, which is a global epidemic prevalent in two-thirds of the adult population. The monoclonal antibody raised against peptide 19 (Pep19: TLVVNRLRGSLKICAVKAPG) from P. gingivalis HSP60 was polyreactive to the human homolog. The aim of this study was to determine if Pep19 from P. gingivalis HSP60 manifests itself as a predominant antigen in infection-triggered autoimmune diseases. Pep19 from P. gingivalis HSP60, Mycobacterium tuberculosis HSP60 and Chlamydia pneumoniae HSP60 was synthesized for comparative recognition by the sera from patients with atherosclerosis, type 2 diabetes and rheumatoid arthritis, all with ongoing periodontal disease, and by the sera of a control group of patients with periodontal disease but with no history of atherosclerosis, type 2 diabetes or rheumatoid arthritis. Of the Pep19 peptides from P. gingivalis HSP60, M. tuberculosis HSP60 and C. pneumoniae HSP60, Pep19 from P. gingivalis HSP60 was the peptide epitope predominantly and most consistently recognized by the serum samples of the four disease groups (chronic periodontitis, atherosclerosis, type 2 diabetes mellitus and rheumatoid arthritis). Seroreactivity to Pep19 of P. gingivalis HSP60, an oral pathogen, was predominant in patients with autoimmune disease with ongoing periodontal disease.


[The intervention of ginkgo biloba extract on monocrotaline-induced right ventricular hypertrophy in rats and its mechanism].
To study the protective effects of ginkgo biloba extract on the right ventricular hypertrophy. Seventy-two SD male rats were randomly divided into 3 groups: control group(CON), monocrotaline-induced right ventricular hypertrophy group (MCT) and ginkgo biloba extract treated group (EGB) (n=24 in each group). Group MCT and group EGB were intraperitoneally injected with 2%MCT at the dose of 60 mg /kg on the first day. From the second day, group MCT was injected with 2 ml 0.9% sodium chloride, and 60 mg/kg ginkgo leaf extract was administered to the stomach in group EGB. The control group was injected with 2 ml 0.9% sodium chloride on the first day. After 3 weeks, in each group,cardiac hemodynamic changes were measured, heart weight index was calculated, and myocardial pathological changes were observed by HE staining. The expression of TRPC6 was detected by real-time polymerase chain reaction (real-time -PCR) and Western blot. Compared with the control group, the right ventricular systolic pressure (RVSP) was increased significantly in the MCT group(P<0.01), the maximum or decline rate of descent (RV ±dp/dtmax) of the right ventricle pressure was increased significantly(P<0.01), while the EGB group had the same trend as all the indexes in the group MCT, but the amplitude of all indicators in group EGB were decreased significantly than those of group MCT(P<0.01), and the right ventricular hypertrophy index (RVMI) in group EGB was significantly lower than that in group MCT(P<0.01).Group MCT showed typical myocardial hypertrophy performance by HE staining, and the right ventricular myocytes in group EGB were significantly improved than that in group MCT, and the mRNA and protein expression levels of TRPC6 in the right ventricle of group MCT and group EGB were increased(P<0.01), while the EGB group was significantly lower than that of the MCT group(P<0.01). Ginkgo biloba extract may inhibit the signal pathway of CaN / NFAT in cardiac myocytes by reducing the expression of TRPC6 protein, and then play an early protective effect on myocardial hypertrophy.


Menstrual pattern following tubal sterilization.
We sought to investigate the effects of tubal sterilization over menstrual parameters and determine the timing of the detected influences. We questioned 97 voluntary patients among 301 women who had been subjected to tubal sterilization in our clinic between 1996-2006. Patients were asked via questionnaire about menstrual parameters concerning the 5 years before and after the surgery, which focused on each year separately. Statistical analyses were carried out by considering the preoperative data of patients as controls and postoperative data as the study group. Some kind of pattern change was detected in 7.6% of all patients. Hemorrhage with chunky clots of blood incidence decreased significantly by the second postoperative year (31.9%, 21.6%; P<.05). We had a significant decrease in dysmenorrhea postoperatively in the third, fourth, and fifth years (38.1%, 21.6%, 16.4%, 13.4%; P<.05). While the premenstrual syndrome was 45.3% before surgery, it was 30.9% and 24.7% postoperatively in the fourth and fifth years (P<.05). Hemorrhage and dysmenorrhea were most frequently seen after tubal sterilization. The statistically significant drop in the mean weekly coital frequency during postoperative period indicates a need for further studies, which might evaluate the reasons behind this reduction.


Cardiac function assessed by gated heart pool studies in an alcohol clinic population: a preliminary study.
The nuclear gated heart pool scan was used to assess the left ventricular ejection fraction (LVEF) in 19 patients attending the Drug and Alcohol Unit for treatment of their alcoholism. Eighteen of the patients were asymptomatic and had no signs of cardiac impairment. In 14 subjects (13 asymptomatic), the LVEF was subnormal. Repeat studies were performed in 10 of the subjects following a period of 4-9 months of reduced intake of alcohol or abstinence. The LVEF improved in four subjects, remained unchanged in four, and actually decreased in two others despite a reduction in reported alcohol intake.


A spectrally tunable microstructured optical fibre Bragg grating utilizing an infiltrated ferrofluid.
The spectral response of a Bragg grating reflector inscribed in a microstructured optical fibre is tuned by employing an infiltrated ferrofluid, while modifying the overlap of the ferrofluidic medium with the grating length. Significant spectral changes in terms of Bragg grating wavelength shift and extinction ratio were obtained under static magnetic field actuation. Spectral measurements revealed non-bidirectional propagation effects dependent upon the relative position between the ferrofluid and the grating. The actuation speed of the device was measured to be of the order of few seconds.


Pulmonary coccidioidal mycetoma.
Cavitary pulmonary disease due to coccidioidomycosis is common; however, development of both the underlying cavity and the fungus ball due to Coccidioides immitis is rare and has been reported on only five occasions. We report a case of coccidioidal mycetoma formation as a late sequelae of primary pulmonary coccidioidal pneumonia. Therapy with 2 gm of amphotericin B was unsuccessful and, because of recurrent hemoptysis, the patient required lobar resection. Endosporulating spherules, as well as septate mycelia with arthrospore formation, were found on histologic examination. The medical and surgical management, as well as the potential of such lesions to produce human to human transmission, is discussed.


[Potential therapeutic target for pulmonary arterial hypertension--osteopontin].
Microarray analysis demonstrated lung gene encoding osteopontin (OPN), a soluble secreted phosphoprotein, was significantly elevated in rats with hypoxic pulmonary arterial hypertension (PAH). Since OPN enhances vascular smooth muscle cell proliferation, we hypothesized that OPN played a role in the pathogenesis of PAH. Some patients with idiopathic PAH showed increased expression of plasma OPN and lung OPN gene. OPN overexpression in mice caused pronounced pulmonary hypertension and vascular remodeling under hypoxic conditions. A PPARgamma ligand, pioglitazone, which was reported to inhibit OPN gene expression in vitro, attenuated hypoxia-induced increase in lung OPN gene and pulmonary vascular remodeling in rats. These findings indicate that OPN may be responsible for pulmonary vascular remodeling and could be a therapeutic target for PAH.


[The importance of the long pelvis in clinical practice and medical education (author's transl)].
The importance of the long pelvis with lumbo-sacral assimilation in obstetrics is evaluated. 111 x-rays of the pelvis in cases with abnormal deliveries were evaluated and compared to the clinical data. The incidence of the long pelvis was not increased in the total group, nor in the 100 cases with abnormal deliveries. A long pelvis was present in 30.2% of the 43 breech presentations. In 4 cases with a funnel pelvis vaginal delivery occurred without difficulty. In 42 posterior vertex presentation the long pelvis appears to have a pathogenetic importance regarding the primary posterior position. The further course of the delivery was not influenced by the long pelvis. In 7 cases of low transverse arrest, 4 had a long pelvis but only 1 had a funnel pelvis to explain this abnormal position. In summary, the long pelvis even in its most severe form, the funnel pelvis, does not block the adaptation processes in the lesser pelvis. The changes in the pelvic inlet due to the lumbo-sacral assimilation have an etiologic importance on the initial presentation at the inlet such as breech presentation, military vertex presentation, brow presentation, or Roederers anomaly. However, no prognostic value for the mechanism of the delivery can be derived from the initial presentation. The delivery dose not depend on the long pelvis but on the malpresentation when delivery becomes necessary.


[Multiple hepatosplenic abscesses caused by Yersinia enterocolitica in a patient with hemochromatosis].
Yersinia enterocolitica is a gram-negative bacillus that thrives in conditions associated with iron overload. We describe an unusual case of a diabetic patient with a previously unrecognized hemochromatosis presenting with Y. enterocolitica septicemia. He was admitted because of a 10 day history of abdominal pain, fever and jaundice. Blood cultures grew Y. enterocolitica. The abdomen CT scan showed multiple liver and splenic abscesses. Antibiotic treatment with ciprofloxacin (2 months) resulted in a good clinical response. Serum iron studies showed iron overload. Liver biopsy revealed moderate fibrosis and early cirrhosis with large amounts of hemosiderin granules deposited in hepatocytes and bile duct epithelium. This report reviews the literature and highlights that iron overload must be ruled out in Yersinia septicemia patients.


Mechanisms that control antigen receptor variable region gene assembly.
The somatic assembly of antigen receptor genes--known as V(D)J recombination--is a highly regulated process at several different levels. V(D)J rearrangement is limited to stages of early B and T cell development by the lymphoid specific expression of recombinase activity. A common recombinase is apparently responsible for the rearrangement of all antigen receptor loci. Thus, the tissue specific and ordered rearrangement of each antigen receptor locus must depend on controlling their 'accessibility' to the recombinase. Here, we outline recent work that has contributed to the current understanding of mechanisms that control V(D)J rearrangement.


[Tularemia after tick bite in Vestfold].
Direct contact with rodents or their faeces is a well-known risk factor for contracting tularaemia in Norway. Both insects and ticks can act as vectors of tularaemia, but transmission by this route has not previously been described in this country. We report three cases of serologically confirmed ulceroglandular tularaemia on a small island in Southern Norway, an area in which tularaemia has not previously been known to occur. Tick bites preceded infection in two of the patients. The third patient may also have become infected through a tick or insect bite. Diagnosis was made late in all cases, causing a delay in appropriate treatment. Two of the patients were successfully treated with ciprofloxacin. Our experience and previous reports suggest that quinolones should be considered as the first choice of drugs in the treatment of tularaemia in Norway.


[Drying time for human saliva].
In a case of aggravated extortion under threat of force, the medicolegal expert was asked to give an opinion on the drying time of human saliva. Fresh traces of saliva were applied to composite stones similar to those at the scene of the crime and their drying behavior was examined in a climate test chamber. Air temperature and air humidity during the experiment corresponded to the values of the measuring station located nearest to the crime scene. After one hour and 40 minutes no salivary spots were discernible on the stones any more. Depending on various influence factors, the traces could have originated both at the time of the offence and within a time window of up to 3 hours before.


Identification of an Oxidative Stress-Related LncRNA Signature for Predicting Prognosis and Chemotherapy in Patients With Hepatocellular Carcinoma.
Background: Oxidative stress plays a critical role in oncogenesis and tumor progression. However, the prognostic role of oxidative stress-related lncRNA in hepatocellular carcinomas (HCC) has not been fully explored. Methods: We used the gene expression data and clinical data from The Cancer Genome Atlas (TCGA) database to identify oxidative stress-related differentially expressed lncRNAs (DElncRNAs) by pearson correlation analysis. A four-oxidative stress-related DElncRNA signature was constructed by LASSO regression and Cox regression analyses. The predictive signature was further validated by Kaplan-Meier (K-M) survival analysis, receiver operating characteristic (ROC) curves, nomogram and calibration plots, and principal component analysis (PCA). Single-sample gene set enrichment analysis (ssGSEA) was used to explore the relationship between the signature and immune status. Finally, the correlation between the signature and chemotherapeutic response of HCC patients was analyzed. Results: In our study, the four-DElncRNA signature was not only proved to be a robust independent prognostic factor for overall survival (OS) prediction, but also played a crucial role in the regulation of progression and chemotherapeutic response of HCC. ssGSEA showed that the signature was correlated with the infiltration level of immune cells. HCC patients in high-risk group were more sensitive to the conventional chemotherapeutic drugs including Sorafenib, lapatinib, Nilotinib, Gefitinib, Erlotinib and Dasatinib, which pave the way for targeting DElncRNA-associated treatments for HCC patients. Conclusion: Our study has originated a prognostic signature for HCC based on oxidative stress-related DElncRNAs, deepened the understanding of the biological role of four key DElncRNAs in HCC and laid a theoretical foundation for the choice of chemotherapy.


Polysilicon Microchips Functionalized with Bipyridinium-Based Cyclophanes for a Highly Efficient Cytotoxicity in Cancerous Cells.
The use of micrometric-sized vehicles could greatly improve selectivity of cytotoxic compounds as their lack of self-diffusion could maximize their retention in tissues. We have used polysilicon microparticles (SiμP) to conjugate bipyridinium-based compounds, able to induce cytotoxicity under regular intracellular conditions. Homogeneous functionalization in suspension was achieved, where the open-chain structure exhibits a more dense packing than cyclic analogues. The microparticles internalized induce high cytotoxicity per particle in cancerous HeLa cells, and the less densely packed functionalization using cyclophanes promotes higher cytotoxicity per bipy than with open-chain analogues. The self-renewing ability of the particles and their proximity to cell membranes may account for increased lipid peroxidation, achieving toxicity at much lower concentrations than that in solution and in less time, inducing highly efficient cytotoxicity in cancerous cells.


Effects of Periprocedural Tirofiban vs. Oral Antiplatelet Drug Therapy on Posterior Circulation Infarction in Patients With Acute Intracranial Atherosclerosis-Related Vertebrobasilar Artery Occlusion.
Background and purpose: Tirofiban and oral antiplatelet drugs can be used to inhibit reocclusion and restore microvascular reperfusion during endovascular treatment (EVT). This study compared recanalization rates, symptomatic intracranial hemorrhage (SICH), 90 day mortality, and functional outcomes between periprocedural tirofiban and antiplatelet therapy in patients with acute intracranial atherosclerosis-related vertebrobasilar artery occlusion. Methods: A total of 105 consecutive patients with acute intracranial atherosclerosis-related vertebrobasilar artery occlusion who underwent EVT + tirofiban + oral antiplatelet or EVT + oral antiplatelet therapy at the Beijing Tiantan Hospital between January 2012 and July 2018 were included. Baseline characteristics, procedural parameters, and functional outcomes were assessed. Results: Among the 105 patients, 74 underwent EVT + tirofiban + oral antiplatelet therapy, while 31 underwent EVT + oral antiplatelet drug therapy. EVT + tirofiban + oral antiplatelet therapy resulted in higher recanalization rates compared to EVT + oral antiplatelet drug therapy (93.24% vs. 77.42%; p = 0.038), whereas the risk for SICH, 90 day mortality, and functional independence outcomes did not differ between the groups. Logistic regression analysis revealed that EVT + tirofiban + oral antiplatelet therapy had an increased probability of higher recanalization rates (OR 0.18 [95% confidence interval (CI) 1.24-24.39]; p = 0.025). There were no differences in SICH (OR 0.00 [95% CI 0.00-Inf]; p = 0.998), 90 day mortality (OR 1.19 [95% CI 0.17-4.05]; p = 0.826), or functional independence (modified Rankin score 0 to ≤ 2) (OR 1.43 [95% CI 0.23-2.17]; p = 0.538) between the groups. Conclusions: Ninety day functional outcomes of EVT + tirofiban + oral antiplatelet therapy were not superior to those of EVT + oral antiplatelet drug therapy; however, the recanalization rate was higher and the risks for SICH and 90 day mortality were lower.


Effects of enrichment predominate over those of chronic stress on fear-related behavior in male rats.
The ability to discriminate between spatial contexts is crucial for survival. This ability can be succinctly tested in the paradigm of fear renewal. In this paradigm, a change of spatial context results in robust renewal of conditioned fear, even if the conditioned fear has been previously extinguished. Chronic stress and environmental enrichment are known to affect learning and memory in opposite directions, with the former generally being deleterious. In this study, we examined the effects of chronic stress and enrichment on fear renewal in rats. Fear was evaluated as freezing responses to an auditory conditioning stimulus initially associated with footshocks in context A; fear extinction was evaluated in a novel spatial context (B) without the conditioned stimulus, and renewal in a third context (C) with the auditory cue. Specifically, we aimed to test if environmental enrichment can oppose the effects of chronic stress on fear renewal. We exposed different groups of adult male Wistar rats (6-12 per group) to 10 days of chronic stress (immobilization for 2 h daily), 14 days of enrichment, or a combination of both. We report that chronic stress compromised fear extinction and renewal. In contrast, enrichment re-established fear renewal in chronically stressed rats. Enhanced contextual modulation of fear memories in animals experiencing environmental enrichment while stressed could reflect an adaptive response. This could allow greater flexibility to optimize vigilance in differing spatial contexts.


[Effects of anti-androgens on sexual function. Double-blind comparative studies on allylestrenol and chlormadinone acetate. Part II: Self-assessment questionnaire method].
Allylestrenol (ALE) and chlormadinone acetate (CMA) were administered to patients with prostatomegaly by the double-blind method, and a self-assessment questionnaire method developed by the authors was used to study the influence of these two antiandrogens on their sexual function. Each test drug was orally administered to 58 patients, in a daily dosage of 50 mg for 12 consecutive weeks. The questionnaires consisted of 6 categories each consisting of 5 questions, or 30 questions in total. The 6 categories were "sexual desire," "erectile capacity" and "ejaculation," which relate to the sexual function, and "living environment (including the frequency of sex)," "dysuria" and "dummy (personality)." Each question was graded into 0-10 points, and each patient was requested to circle the number which best described his status. The scores were compiled and statistically analyzed. Many patients were senile. Evaluable answers were obtained for 99 (85.3%) of the 116 patients. Factor analysis based on the preadministration scores confirmed the contents of the questionnaires to be appropriate for the objectives of the present study. Multiple regression analysis revealed a high correlation between the self-assessment scores and objective data (nocturnal penile tumescence values; NPT values) when dropout cases due to a decrease in the sexual function and non-replying cases were excluded. The self-assessment questionnaire method was concluded to be as useful an objective test method as the NPT measurement for examining the sexual function. Aggravation of the "frequency of urination during night" was conspicuous in the CMA group, and there was a significant difference (p less than 0.05) in this parameter between the two groups. Except for this parameter, dysuria was improved in both administration groups, and there was no significant difference in the efficacy of the two drugs. Both drugs tended to suppress overall sexual function, but the suppression was less severe in the ALE group. Especially the suppression was significantly (p less than 0.05) lower in the ALE group regarding the 3 parameters of "contact sexual arousal," "contact erection" and "morning erection", which are included in the category of "sexual desire" or "erectile capacity." Also, suppression of "frequency of sex" and "intensity of sexual desire" tended to be lower in the ALE group at a level of significance of p less than 0.1. Regarding questions in the category of "ejaculation," the incidence of non-replies was high in both groups, but its rate was higher in the CMA group.


Exploratory evidence for differences in GABAergic regulation of auditory processing in autism spectrum disorder.
Altered reactivity and responses to auditory input are core to the diagnosis of autism spectrum disorder (ASD). Preclinical models implicate ϒ-aminobutyric acid (GABA) in this process. However, the link between GABA and auditory processing in humans (with or without ASD) is largely correlational. As part of a study of potential biosignatures of GABA function in ASD to inform future clinical trials, we evaluated the role of GABA in auditory repetition suppression in 66 adults (n = 28 with ASD). Neurophysiological responses (temporal and frequency domains) to repetitive standard tones and novel deviants presented in an oddball paradigm were compared after double-blind, randomized administration of placebo, 15 or 30 mg of arbaclofen (STX209), a GABA type B (GABAB) receptor agonist. We first established that temporal mismatch negativity was comparable between participants with ASD and those with typical development (TD). Next, we showed that temporal and spectral responses to repetitive standards were suppressed relative to responses to deviants in the two groups, but suppression was significantly weaker in individuals with ASD at baseline. Arbaclofen reversed weaker suppression of spectral responses in ASD but disrupted suppression in TD. A post hoc analysis showed that arbaclofen-elicited shift in suppression was correlated with autistic symptomatology measured using the Autism Quotient across the entire group, though not in the smaller sample of the ASD and TD group when examined separately. Thus, our results confirm: GABAergic dysfunction contributes to the neurophysiology of auditory sensory processing alterations in ASD, and can be modulated by targeting GABAB activity. These GABA-dependent sensory differences may be upstream of more complex autistic phenotypes.


Low Energy Turnover of Physically Inactive Participants as a Determinant of Insufficient Mineral and Vitamin Intake in NHANES.
Micronutrient requirements do not scale linearly with physical activity-related energy expenditure (AEE). Inactive persons may have insufficient micronutrient intake because of low energy intake (EI). We extracted data from NHANES 2003-2006 on 4015 adults (53 ± 18 years (mean ± SD), 29 ± 6 kg/m², 48% women) with valid physical activity (accelerometry) and food intake (2 × 24 h-dietary recall) measures. Total energy expenditure (TEE) was estimated by summing the basal metabolic rate (BMR, Harris-Benedict), AEE, and 10% of TEE for the thermic effect of food, to calculate the physical activity levels (PAL = TEE/BMR). Energy intake (EI) was scaled to match TEE assuming energy balance. Adjusted food intake was then analyzed for energy and micronutrient content and compared to estimated average requirements. The NHANES population was physically insufficiently active. There were 2440 inactive (PAL < 1.4), 1469 lightly to moderately active (PAL1.4 < 1.7), 94 sufficiently active (PAL1.7 < 2.0), and 12 very active participants (PAL ≥ 2.0). The inactive vs. active had significantly lower intake for all micronutrients apart from vitamin A, B12, C, K, and copper (p < 0.05). The inactive participants had insufficient intake for 6/19 micronutrients, while the active participants had insufficient intake for 5/19 (p < 0.05) micronutrients. Multiple linear regression indicated a lower risk for insufficient micronutrient intake for participants with higher PAL and BMI (p < 0.001). Symmetrical up-scaling of PAL and EI to recommended physical activity levels reduced the frequency of micronutrient insufficiencies. It follows that prevalence of insufficient micronutrient intake from food in NHANES might be partly determined by low energy turnover from insufficient PAL.


Elastase and alkaline protease production by Pseudomonas aeruginosa strains: comparison of two procedures.
Pseudomonas aeruginosa is an opportunistic pathogen that can cause fatal infections in immunocompromised hosts. The virulence of P. aeruginosa is associated with the presence of various extracellular factors like elastase and alkaline protease. These enzymes are suggested to contribute to tissue destruction and assist bacterial invasion during infection. Therefore it seems likely that determination of these virulence factors will be an important prognostic marker in the near future especially for follow up of cystic fibrosis patients, to start antimicrobial agents that are directly or indirectly inhibit microbial growth or virulence factor production. Herein, we suggest a simple test procedure to be used in routine laboratories for estimation of elastase and alkaline protease levels and compare them with quantitative methods in the literature. We detected the amount of elastase and alkaline protease in 49 clinical P. aeruginosa isolates by comparing agar plate method and colorimetric assay. The resulting values were in the range reported in the literature and differed from one strain to another(elastase: 0-1390 mg/ml, alkaline protease: 0- 770 mg/ml). Linear relationships were found when assays compared in pairs and significant correlation coefficients were obtained(r>0.788 for alkaline protease, p<0.0001- r>0.926 for elastase, p<0.0001). Our method can be applied in laboratories regardless of the availability of technical equipment.


Method effects of the relation between family history of alcoholism and parent reports of offspring impulsive behavior.
There is an extensive, albeit inconsistent, literature on the relation between parental alcoholism and offspring impulsive behavior. The reasons for this inconsistency are likely multiple but it seems probable that method effects due to different methodological approaches might explain some of the inconsistencies. Offspring behavior is typically assessed based on informant reports. However, no specific method has been demonstrated as optimal for analyzing informant reports, and conclusions may differ depending on the method used. The present study compared findings derived from a multi-informant method proposed by Bauer et al. (2013) to other structural equation models. Participants came from Wave 7 of the Alcohol, Health and Behavior study and included mother and father reports of offspring impulsive behavior on the Health and Behavior Questionnaire (Armstrong, Goldstein, & the MacArthur Working Group on Outcome Assessment, 2003). There were 368 offspring (50% female, age range 3-17 years, meanage = 6.78, SDage = 3.07) from 205 families. The multi-informant model and the single-reporter models each provided a good fit of the data; however, findings differed based on the approach employed. Specifically, the mother-only report model found that offspring with a family history of alcoholism (FHA) were more impulsive compared to offspring without a FHA; no effect of FHA was found in the other single-reporter models. Ratings of offspring impulsive behavior were higher on the father perspective factor suggesting alcoholic fathers were biased in their reports. These findings highlight the relation between FHA and impulsive behavior varies depending on the analytic method used.


Rapid and sensitive surface-enhanced Raman spectroscopy (SERS) method combined with gold nanoparticles for determination of paraquat in apple juice.
Paraquat, a highly efficient herbicide, is widely used in agricultural practices throughout the world. However, paraquat residues in food pose a threat to human health. In order to develop a rapid and sensitive method, surface-enhanced Raman spectroscopy (SERS) coupled with gold nanoparticles was applied to analysis of paraquat in apple juice. Natural organic compounds (sugars and organic acids) in apple juice interfered with SERS measurement. Sample preparation was needed. Paraquat could be detected at concentrations as low as 0.02 and 0.1 µg mL- 1 with the weak cation-exchange solid-phase extraction (WCX-SPE) method and dilution method for sample preparation, respectively. For quantitative analysis, the R2 cv of the partial least-squares regression model with the dilution method (0.939) was not as good as with the WCX-SPE method (0.984), but the dilution method is much less costly, simpler and time saving. Satisfactory recovery values were obtained ranging from 94.73% to 114.81%, with the exception of 56.55% for the lowest concentration. This work showed that SERS combined with gold nanoparticles could determine paraquat in apple juice. As a simple, rapid and ultrasensitive method, it has great practical potential for detection of other contaminants in a variety of foods. © 2018 Society of Chemical Industry.


Adequacy of tissue oxygenation in intact dog intestine.
Changes in O2 consumption, O2 extraction, and intramural pH, resulting from a decreasing O2 delivery, were studied in the intact dog intestine. The O2 delivery was decreased by ischemia, hypoxia, and combined hypoxia-ischemia. A noninvasive approach for determining intramural pH based on the principle of tonometry was used. There was a strong correlation between the changes in intramural pH and intestinal O2 consumption as O2 delivery was decreased. Intramural pH and O2 consumption were initially maintained in the face of decreasing O2 delivery, but after a critical point they decreased. This critical point was 60.3 +/- 1.6% of base-line O2 delivery in the ischemic group and 51.3 +/- 2.7% of base line in the hypoxic-ischemic group. Despite a decrease to 36.0 +/- 5.6% of base-line O2 delivery, the intramural pH and O2 consumption did not decrease in the hypoxic group. O2 extraction increased with decreasing O2 delivery but did not plateau, indicating no diffusion limitation. The data suggest that blood flow is the major factor limiting intestinal O2 consumption. It is concluded that the noninvasive measure of intramural pH is a good marker of the adequacy of tissue oxygenation in canine intestine.


Effects of phytoestrogens on sarcoplasmic/endoplasmic reticulum calcium ATPase 2a and Ca2+ uptake into cardiac sarcoplasmic reticulum.
Phytoestrogens are naturally occurring estrogenic compounds found in plants and plant products. These compounds are also known to exert cellular effects independent of their interactions with estrogen receptors. We studied the effects of the phytoestrogens phloretin, phloridzin, genistein, and biochanin A on Ca(2+) uptake into the cardiac muscle sarcoplasmic reticulum (SR). Genistein and biochanin A did not affect SR Ca(2+) uptake. On the other hand, phloretin and phloridzin decreased the maximum velocity of SR Ca(2+) uptake but did not affect the Hill coefficient or the Ca(2+) sensitivity of uptake. Measurements of the ATPase activity of the cardiac SR Ca(2+) pump (SERCA2a) revealed direct inhibitory effects of phloretin and phloridzin on SERCA2a. Neither compound induced a detectable change in the permeability of the SR membrane to Ca(2+). These results indicate that phloretin and phloridzin inhibit cardiac SR Ca(2+) uptake by directly inhibiting SERCA2a.


Heat- and cold-inducible regulation of HSP70 expression in zebrafish ZF4 cells.
Elevated temperature induces a rapid heat shock transcription factor (HSFs)-mediated expression of heat shock (hsp) genes. The effect of cold exposure on hsp gene expression has hardly been investigated, although ectothermic animals experience both cold and heat stress. We have previously shown in zebrafish that the expression of hsf1a and a unique isoform hsf1b vary in a tissue-specific manner upon heat stress. In the current study, using a zebrafish (Danio rerio) embryonic cell line (ZF4), we have compared the effects of heat shock (28-->37 degrees C) vs. cold shock (28-->20 degrees C) on the expression of ahsf1a, zhsf1b and hsp70. Concomitantly, the suitability of the ZF4 cells as a model system was verified. The expression pattern of HSP70 proteins following heat or cold exposure is distinct, and the total HSP70 level is upregulated or stable, respectively. Moreover, heat exposure specifically increases the ratio of zhsf1a/b expression (10-fold), whereas cold exposure decreases it to one half. These data suggest that the zhsf1a/zhsf1b ratio is regulated in a temperature-dependent manner, and the ratio may be indicative of the stressor-specific HSP70 expression. Furthermore, the response in ZF4 cells upon heat shock resembles the response observed in zebrafish liver and thus, supports the use of this cell line in stress response studies.


The predictors of poor outcomes in patients with femoral artery injuries.
This study investigated the predictors of poor outcomes, including limb loss and death, in patients with femoral artery injuries. The study included 158 patients aged 2-82 (mean age 28.4 ± 16.5) with femoral arterial injury (common, deep, and superficial femoral artery) that were treated surgically between 2000 and 2010. Isolated venous injuries were excluded. Demographic and clinical data of the patients, including age, gender, admission time, pulse rate and blood pressure, hematocrit value, reason of injury, associated injury, and Mangled Extremity Severity Score (MESS) were recorded. Of the 158 patients, the death and amputation rates were 5.7% (9) and 5.1% (8), respectively. In logistic regression analysis, four variables (pulse rate, MESS, hematocrit, and bone trauma) were found to be independent predictors for poor outcomes. The Odd's ratios and confidence interval values of these variables were as follows: 7.24 (1.94-26.92), 21.75 (5.41-87.48), 5.93 (3.04-11.54) and 7.46 (2.09-9.56), respectively. The MESS value, presence of bone fracture, hematocrit, and pulse rate on admission are predictive risk factors for poor outcomes in patients with femoral artery injury. Therefore, in these patients, prompt intervention by experienced surgeons is crucial for limb salvage and decreased mortality.


Synchronous endoscopy and microsurgery: a novel strategy to approach complex ventricular lesions. Report of three cases.
Simultaneous endoscopic and microsurgical (synchronous) approaches represent a new paradigm in the treatment of complex ventricular lesions. This technique is well suited for lesions that involve multiple ventricular or cisternal compartments, have a nonlinear axis, or adhere to critical anatomical or neurovascular structures. Two distinct operative corridors, one endoscopic and the other microsurgical, are used during synchronous approaches to address such lesions, increasing the likelihood of a safe and complete resection. The authors present the cases of two children and an adult treated via synchronous approaches. All patients had multi-compartmental lesions involving the ventricles and/or cisterns. One patient presented with a suprasellar Rathke cyst with a significant third ventricular component, one with a hypothalamic hamartoma having a substantial cisternal component, and the remaining patient with a choroid plexus papilloma in the left lateral ventricle that extended from midbody to the temporal horn. In the cases of the Rathke cyst and the hamartoma, debulking in the third ventricle and controlled detachment of the lesion from the hypothalamus were undertaken using endoscopy, and simultaneous resection of the suprasellar component was performed through a subfrontal craniotomy. In the case of the choroid plexus papilloma, selective cautery of the choroidal feeding vessels and detachment from the temporal tela choroidea were performed using endoscopy, and the tumor from the ventricular body to the atrium was resected via a craniotomy. In each case the resection concluded with the intersection of endoscopic and microsurgical fields. All three patients had good outcomes. Endoscopic and microsurgical approaches can be used concurrently to treat multicompartment ventricular and/or cisternal lesions with good results. The probable advantages of this method are more complete resection and improved safety.


Peripheral neural synchrony in post-lingually deafened adult cochlear implant users.
We recently developed a noninvasive method for quantifying neural synchrony in the cochlear nerve (i.e., peripheral neural synchrony) in cochlear implant (CI) users, which allows for evaluating this important physiological phenomenon in human CI users for the first time in the literature. This paper reports this new method in detail. In addition, this study assessed how peripheral neural synchrony was correlated with temporal resolution acuity and speech perception outcomes measured in quiet and in noise in post-lingually deafened adult CI users. It tested the hypotheses that 1) the degree of peripheral neural synchrony varied among CI users, and 2) peripheral neural synchrony was an important factor for temporal resolution acuity and speech perception outcomes in noise in post-lingually deafened adult CI users. Study participants included 18 post-lingually deafened adult CI users with a Cochlear™ Nucleus® device. Two study participants were implanted bilaterally, and each ear was tested separately. For each of the 20 ears tested in this study, peripheral neural synchrony, quantified using an index named the phase locking value (PLV), was measured at four electrode locations across the electrode array (default electrodes: 3, 9, 15 and 21) based on 400 sweeps of the electrically evoked compound action potential (eCAP). The PLV is a measure of trial-by-trial phase coherence among eCAP sweeps/trials and quantifies the degree of peripheral neural synchrony. Temporal resolution acuity was evaluated by measuring the within-channel gap detection threshold (GDT) using a three-alternative, forced-choice procedure, targeting 79.4% correct on the psychometric function in a subgroup of 9 participants (10 ears). For each ear tested in these participants, GDTs were measured at two electrode locations with a large difference in PLVs. For 15 ears tested in 14 participants, speech perception performance was evaluated using Consonant-Nucleus-Consonant (CNC) word lists presented in quiet and in noise at signal-to-noise ratios (SNRs) of +10 and +5 dB. A Linear Mixed-effects Model (LMM) was used to evaluate the effect of electrode location on the PLV after controlling for the stimulation level effect. A partial correlation test was used to evaluate the association between the PLV and GDT while controlling for the effect of stimulation level on GDT. GDTs measured for electrode pairs with different PLVs were compared using a paired-samples t-test. The association between PLVs and CNC word scores measured in different conditions, as well as the association between the PLV and the degree of noise effect on CNC word scores were evaluated using Pearson product-moment correlation tests with Bonferroni correction for multiple comparisons. PLVs varied substantially across study participants and electrode locations. There was a significant correlation between the PLV and GDT, where higher PLVs were associated with lower GDTs. PLVs were not significantly correlated with CNC word scores measured in any listening condition or the effect of competing background noise presented at a SNR of +10 dB on CNC word scores. In contrast, there was a moderate, negative correlation between the PLV and the degree of noise effect on CNC word scores for a competing background noise presented at a SNR of +5 dB. This newly developed method can be used to assess peripheral neural synchrony in living CI users, a physiological phenomenon that potentially plays a vital role in determining auditory perception outcomes in electrical hearing. Poorer peripheral neural synchrony is associated with lower temporal resolution acuity and larger detrimental effect of competing background noise on speech perception performance in post-lingually deafened adult CI users.


[Analysis of the correlation between chewing side preference and disc displacement types and clinical symptoms in patients with anterior disc displacement of temporomandibular joint].
Objective: To analyze the clinical symptoms and types of disc displacement of patients with anterior disc displacement (ADD) of temporomandibular joint (TMJ) and to explore the correlation between chewing side preference (CSP) and the clinical symptoms and types of disc displacement of ADD patients. Methods: This was a cross-sectional study of the ADD patients diagnosed by clinical symptoms and MRI findings of TMJ in the Department of Stomatology, General Hospital of Chinese PLA from January 2018 to December 2019. A total of 111 ADD patients [33 males and 78 females, aged(31.0±10.9) years old] were included. The patients were divided into two groups according to whether they had CSP: non-CSP group (n=40) and CSP group (n=71). The clinical symptoms and types of ADD were observed and recorded. According to the specific side of CSP in the CSP group, the patients were further divided into the ipsilateral side and the contralateral side of CSP. The pain, TMJ sounds and the ADD types were also observed. Chi square test was used to compare the pain, TMJ sounds, limited mouth opening and ADD types of the two groups. Binary Logistic regression model was used to analyze the correlation between CSP and clinical symptoms and ADD characteristics. Results: The incidence of pain in the CSP group [89% (63/71)] was significantly higher than that in the non-CSP group [70% (28/40)] (P<0.05). In CSP patients, the incidences of pain and joint sounds on the ipsilateral side of CSP were significantly higher than that on the contralateral side (P<0.05). MRI showed that the incidence of bilateral ADD in the CSP group [58%(41/71)] was significantly higher than that in the non-CSP group [37%(15/40)] (P<0.05).There were significant differences in the incidences of no disc displacement (DD), anterior disk displacement with reduction(ADDwR) and anterior disk displacement without reduction (ADDwoR) between ipsilateral and contralateral joints of the CSP patients (P<0.05). There were no significant differences in the incidences of no DD, ADDwR and ADDwoR between left and right joints of the non-CSP patients (P>0.05). The incidence of ADDwoR in ipsilateral side of the CSP patients was significantly higher than that in contralateral side (P<0.05). Pain (OR=3.375) and the side of disc displacement (OR=2.278) in patients with ADD were positively correlated with CSP (P<0.05). Conclusions: The clinical symptoms and types of disc displacement between patients with and without CSP were significantly different. The incidences of pain and bilateral disc displacement in the CSP group were significantly higher than those in the non-CSP group. In addition, the incidences of pain, TMJ sounds and anterior disk displacement without reduction on the ipsilateral side of patients with CSP were significantly higher than those on the contralateral side. The pain symptoms and side of disc displacement were positively related to CSP.


Sub-microsecond photodissociation pathways of gas phase adenosine 5'-monophosphate nucleotide ions.
The sub-microsecond dissociation pathways for the protonated and deprotonated forms of adenosine 5'-monophosphate were probed in the gas phase using a linear time of flight spectrometer. The studies show two dissociation pathways for the AMP ions indicating dominant ergodic pathways in the photodissociation of these species. The photofragmentation was determined to be a single photon process for the AMP ions. Photodetachment of the AMP anion excited at 266 nm was not observed, leaving dissociation as the prominent pathway for relaxation of the excess energy in the biomolecule. The photofragments were analysed at the electrostatic ion storage ring (ELISA) and found to be similar to collision induced fragments in the case of anions but different in the case of cations.


[Influence of avian influenza virus NS1 protein on the expression of IP-10 in BEAS-2B cells].
To investigate the influence of avian influenza virus (AIV) NS1 protein on the expression of interferon-inducible protein 10 (IP-10). NSI gene from virus A/Anhui/1/2005 (H5N1), NS1 gene inserted with 80-84 amino acids from virus A/Anhui/1/2005 (H5N1) and NS1 gene from virus A/Puerto Rico/8/1934 (H1N1) were cloned into the eukaryotic expression vector pEGFP-N1, and transfected into BEAS-2B cells, IP-10 expression level in transfected cells was detected by flow cytometry. Compared with the control group pEGFP-N1, expression of these three different NS1 genes can down-regulate the expression of IP-10 in BEAS-2B cells, but there is no significant difference as to the lower level among them. NS1 protein of A/Anhui/1/2005 (H5N1) can down-regulate the expression level of IP-10, but this may not clarify its relationship with the virulence of AIV.


Selenium and Sulfur to Produce Allium Functional Crops.
Selenium is an element that must be considered in the nutrition of certain crops since its use allows the obtaining of biofortified crops with a positive impact on human health. The objective of this review is to present the information on the use of Se and S in the cultivation of plants of the genus Allium. The main proposal is to use Allium as specialist plants for biofortification with Se and S, considering the natural ability to accumulate both elements in different phytochemicals, which promotes the functional value of Allium. In spite of this, in the agricultural production of these species, the addition of sulfur is not realized to obtain functional foods and plants more resistant; it is only sought to cover the necessary requirements for growth. On the other hand, selenium does not appear in the agronomic management plans of most of the producers. Including S and Se fertilization as part of agronomic management can substantially improve Allium crop production. Allium species may be suitable to carry out biofortification with Se; this practice can be combined with the intensive use of S to obtain crops with higher production and sensory, nutritional, and functional quality.


Creationism and intelligent design.
Creationism, the rejection of evolution in favor of supernatural design, comes in many varieties besides the common young-earth Genesis version. Creationist attacks on science education have been evolving in the last few years through the alliance of different varieties. Instead of calls to teach "creation science," one now finds lobbying for "intelligent design" (ID). Guided by the Discovery Institute's "Wedge strategy," the ID movement aims to overturn evolution and what it sees as a pernicious materialist worldview and to renew a theistic foundation to Western culture, in which human beings are recognized as being created in the image of God. Common ID arguments involving scientific naturalism, "irreducible complexity," "complex specified information," and "icons of evolution," have been thoroughly examined and refuted. Nevertheless, from Kansas to Ohio to the U.S. Congress, ID continues lobbying to teach the controversy, and scientists need to be ready to defend good evolution education.


Extraction of bouton-like structures from neuropil calcium imaging data.
The neuropil, the plexus of axons and dendrites, plays a critical role in operating the circuit processing of the nervous system. Revealing the spatiotemporal activity pattern within the neuropil would clarify how the information flows throughout the nervous system. However, calcium imaging to examine the circuit dynamics has mainly focused on the soma population due to their discrete distribution. The development of a methodology to analyze the calcium imaging data of a densely packed neuropil would provide us with new insights into the circuit dynamics. Here, we propose a new method to decompose calcium imaging data of the neuropil into populations of bouton-like synaptic structures with a standard desktop computer. To extract bouton-like structures from calcium imaging data, we introduced a new type of modularity, a widely used quality measure in graph theory, and optimized the clustering configuration by a simulated annealing algorithm, which is established in statistical physics. To assess this method's performance, we conducted calcium imaging of the neuropil of Drosophila larvae. Based on the obtained data, we established artificial neuropil imaging datasets. We applied the decomposition procedure to the artificial and experimental calcium imaging data and extracted individual bouton-like structures successfully. Based on the extracted spatiotemporal data, we analyzed the network structure of the central nervous system of fly larvae and found it was scale-free. These results demonstrate that neuropil calcium imaging and its decomposition could provide new insight into our understanding of neural processing.


Correlates of depression in chronic dialysis patients: morbidity and mortality.
A group of 74 end-stage renal disease outpatients on dialysis completed on of seven forms of the Depression Adjective Check List (DACL) (Lubin, 1981) once a month over a 12-month period. Patient cooperation in filling out the DACL was 95%, indicating patient's acceptance of this fairly unobtrusive instrument. The distribution of usable DACL scores of 53 patients was trifurcated: high = one SD above the mean; medium +/- one SD from the mean; and low = more than one SD below the mean. A one-way ANOVA on the mean number hospitalizations during the 12-month period for each group was significant, F (2,50) = 8.11, p less than .01. The mean number of hospital admissions was highest for the high depression group and lowest for the low depression group. DACL scores of seven patients who died were significantly higher than for the 46 survivors, t (60) = 4.44, p less than .01.


Hid, Rpr and Grim negatively regulate DIAP1 levels through distinct mechanisms.
Inhibitor of apoptosis (IAP) proteins suppress apoptosis and inhibit caspases. Several IAPs also function as ubiquitin-protein ligases. Regulators of IAP auto-ubiquitination, and thus IAP levels, have yet to be identified. Here we show that Head involution defective (Hid), Reaper (Rpr) and Grim downregulate Drosophila melanogaster IAP1 (DIAP) protein levels. Hid stimulates DIAP1 polyubiquitination and degradation. In contrast to Hid, Rpr and Grim can downregulate DIAP1 through mechanisms that do not require DIAP1 function as a ubiquitin-protein ligase. Observations with Grim suggest that one mechanism by which these proteins produce a relative decrease in DIAP1 levels is to promote a general suppression of protein translation. These observations define two mechanisms through which DIAP1 ubiquitination controls cell death: first, increased ubiquitination promotes degradation directly; second, a decrease in global protein synthesis results in a differential loss of short-lived proteins such as DIAP1. Because loss of DIAP1 is sufficient to promote caspase activation, these mechanisms should promote apoptosis.


Economic impact of different strategies to use sex-sorted sperm for reproductive management in seasonal-calving, pasture-based dairy herds.
To maximize efficiency, profitability, and societal acceptance of modern dairy production, it is important to minimize the production of male dairy calves with poor beef merit. One solution involves using sex-sorted sperm (SS) to generate dairy replacements and breeding all other cows to an easy-calving, short-gestation bull with good beef merit. We used the Pasture Based Herd Dynamic Milk Model to investigate the effect of herd fertility and use of SS on farm net profit in a herd of 100 cows. This was completed by simulating herds with differing fertility performance (good, average, poor), and differing farm reproductive management [conventional semen (CONV) or SS with varying pregnancy per artificial insemination (P/AI) relative to CONV (i.e., relative P/AI 100%, 85%, and 70%)]. As an additional consideration, the method of allocating SS to cows was also examined. The first option used SS on random heifers and cows (S). The second option used SS on heifers and targeted high-fertility cows (SSel). The final option was similar to SSel, but used a fixed-time artificial insemination (AI) protocol to facilitate AI on the farm mating start date (SSync). For CONV, dairy breed semen was used for AI until 50 animals were pregnant (50% chance of a female calf), whereas for S, SSel, or SSync the target number of animals successfully conceiving with SS was set at 28 (based on assumed 90% chance of a female calf from pregnancies derived from SS). Beef breed semen was used on all other dams. The results indicated that the biggest effect on farm net profit was not based on whether or not SS was used, but instead was most affected by the overall fertility performance of the herd. Total farm profit decreased by 10% between the good and average fertility herds, and decreased by a further 12% between the average and poor fertility herds. In almost all situations, when the relative P/AI with SS was ≥85%, use of SS led to an overall increase of the farm net profit. There was an economic benefit of using either SSel or SSync compared with S for the average and poor fertility herds but not for the good fertility herd, highlighting an interaction between SS P/AI and overall herd fertility as well as management practices. If the relative P/AI with SS was <70%, the use of SS led to a decrease in profitability in all simulations except for SSync, highlighting the importance of a good management strategy for use of SS. The findings in this study indicated that SS has significant potential to help facilitate greater integration between the dairy and beef production sectors, as well as increase farm profitability when used appropriately.


[Immunohistochemical analysis of the liver using monoclonal antibodies against intermediate filaments].
The expression of some types of cytokeratin and vimentin in the liver was studied by using monoclonal antibodies to these types of intermediary filaments. Necrotic samples from livers without pathological finding were examined. A panel of 5 monoclonal antibodies, prepared in Czechoslovakia, to cytokeratins Nos. 7,8,18, and 19, as well as to vimentin was used. The findings confirmed the characteristic expression of cytokeratins 8 and 18 in hepatocytes and of cytokeratins 7, 8, 18, and 19 in epithelial cells of intrahepatic bile canaliculi, that monoclonal antibodies prepared in Czechoslovakia (LAMO, Brno and VUKEO, Brno) can be successfully used in immunochemical studies of intermediary filaments in the liver.


Citrate anticoagulation and the dynamics of thrombin generation.
Sodium citrate has been used as an anticoagulant to stabilize blood and blood products for over 100 years, presumably by sequestering Ca(++) ions in vitro. Anticoagulation of blood without chelation can be achieved by inhibition of the contact pathway by corn trypsin inhibitor (CTI). To evaluate the influence of citrate anticoagulation on the performance of blood, platelet-rich and platelet-poor plasma assays. Blood was anticoagulated in three ways: by collection into citrate, CTI and citrate with CTI. Plasma was prepared using each anticoagulation regimen. Functional analyses included calibrated automated thrombography, thromboelastography, plasma clotting, the synthetic coagulation proteome and platelet aggregation. Coagulation reactions were initiated with tissue factor-phospholipid and Ca(++) (when indicated). In all cases, citrate anticoagulation resulted in reaction dynamics significantly altered relative to blood or plasma stabilized with CTI alone. Subsequent experiments showed that calcium citrate itself impairs coagulation dynamics. Coagulation analyses using blood that has been exposed to citrate and recalcified do not yield reliable depictions of the natural dynamics of blood coagulation processes.


PLP2 drives collective cell migration via ZO-1-mediated cytoskeletal remodeling at the leading edge in human colorectal cancer cells.
Collective cell migration (CCM), in which cell-cell integrity remains preserved during movement, plays an important role in the progression of cancer. However, studies describing CCM in cancer progression are majorly focused on the effects of extracellular tissue components on moving cell plasticity. The molecular and cellular mechanisms of CCM during cancer progression remain poorly explored. Here, we report that proteolipid protein 2 (PLP2), a colonic epithelium-enriched transmembrane protein, plays a vital role in the CCM of invasive human colorectal cancer (CRC) epithelium by modulating leading-edge cell dynamics in 2D. The extracellular pool of PLP2, secreted via exosomes, was also found to contribute to the event. During CCM, the protein was found to exist in association with ZO-1 (also known as TJP1) and to be involved in the positioning of the latter at the migrating edge. PLP2-mediated positioning of ZO-1 at the leading edge further alters actin cytoskeletal organization that involves Rac1 activation. Taken together, our findings demonstrate that PLP2, via its association with ZO-1, drives CCM in CRC epithelium by modulating the leading-edge actin cytoskeleton, thereby opening up new avenues of cancer research. This article has an associated First Person interview with the first author of the paper.