Theoretical insights into the properties of amino acid ionic liquids in aqueous solution.
This report presents a systematic investigation of the interactions of water molecule(s) with a series of amino acid cations (Gly(+), Ala(+), Val(+), and Leu(+)), halogen anions (Cl(-), Br(-), BF4 (-), and PF6 (-)), and clusters (GlyCl) n (n = 1-5). The results reveal that H-bonds between amino acid ionic liquids (AAILs) and water molecules are crucial to the properties of aqueous solution of AAILs. The properties of AAIL in water solution depend on the alkyl chain of the amino acid cation, the size of the halogen anion, and the number of water molecules, which provides a certain theoretical basis for the design and application of new AAILs. A series of calculations for some different models showed that quadruple-GlyCl hydrate represents a basic unit for the Gly-water binary system, and can be employed as the simplest model for studying an AAIL-water cluster. On the basis of this model, the effects of water on the hygroscopicity, speed of solubility, viscosity, density, solution enthalpy, and polarity of the AAIL were also predicted. Most importantly, unlike traditional ILs, the novel GlyCl-type AAIL favors interaction of its cationic part, rather than its anionic part, with surrounding water molecules, thus amino acid cationic ILs expand the types of IL available, increasing the choice of ILs for different purposes. We hope that the application of this AAIL in many fields will lead to optimization of this class of compound and be of benefit to the environment. Graphical Abstract Quadruple-GlyCl hydrate represents the basic unit for a GlyCl-water binary system, which can be employed as the simplest model for studying an amino acid ionic liquid (AAIL)-water cluster. The effects of available water on some properties of AAIL are predicted. GlyCl-type AAIL is a novel IL, which prefers its cationic part over its anionic part for interaction with surrounding water molecules. The properties of AAIL in water solution can be adjusted by varying the ion used and the solvent.


Parent behavioral training for problem children: an examination of studies using multiple outcome measures.
The purpose of the present paper was to review parent training studies that have used multiple outcome measures to evaluate treatment effectiveness. Twenty-four studies were identified which used at least two of the following three measures: independent observer-collected data, parent-collected data, and parent-completed questionnaire data. A description of the instruments and procedures used with each assessment technique was presented. The results indicated that all three outcome measures have yielded positive results; however, parent-collected data and parent questionnaire data were associated with more positive outcome results than data collected by independent observers. Limitations of each assessment procedure were discussed and recommendations about which measures to use were made.


The relationship between stiffness and pain following unaccustomed eccentric exercise: the effects of gentle stretch and repeated bout.
To determine how muscle stiffness and pain which develop after eccentric exercise are affected by gentle stretching and repeated exercise. Twenty-one healthy female participants undertook eccentric exercise of the elbow flexors and changes in resting elbow flexion angle (REFA; a measure of muscle stiffness), pain on stretch scale, pain elicited by pressure (PPT pain, a measure of mechanoreceptor hypersensitivity), and upper arm girth were followed for 7 days after exercise. The effects of gentle passive stretching on pain and muscle stiffness were investigated 2 and 4 days after exercise. Eleven participants also repeated the exercise with the same arm 6 weeks after the first bout. There was a significant relationship between the pain on stretch scale and increased REFA (day 4; R2 = 0.65, p < 0.001), whereas there was no relationship between REFA and PPT pain. REFA was reduced by passive stretching and pain on stretch scale was also reduced from 3.0 (1.4, 5.1) to 0.75 (0.0, 2.0) [median (IQR), p = 0.01]. PPT pain was unaffected by the passive stretching, as was muscle swelling. Following the repeated bout, increases in REFA were much reduced, as was pain on stretch scale (p = 0.02). However, PPT pain was not significantly different between the two bouts of exercise. The results indicate that reductions in pain on stretch scale, either by gentle passive stretching or as the result of repeated exercise, are primarily due to reductions in muscle stiffness which develops after eccentric exercise, whereas mechanoreceptor hypersensitivity is relatively unaffected.


Post-awakening cortisol secretion during basic military training.
Salivary free cortisol concentrations in the first 30 min after awakening were assessed in 12 healthy army recruits at the beginning, middle and end of an 11-week intensive physical training course. To ensure strict adherence to protocol saliva collection was supervised and collected on each sampling day immediately on waking and again 15 and 30 min later. Self-rated psychological assessments of state levels of stress, arousal and fatigue were performed in the evening of each sampling day. A within-subjects repeated-measures analysis of participants who completed the course (12 of the original 20) showed a significant main effect of cortisol concentration across all three sampling points after awakening (F((2,22))=54.516, p<0.0001) and a significant main effect of weeks into the training course (F((3,33))=4.390, p=0.010). Further analysis of this effect of measurement-week revealed that at weeks 3 and 6 total cortisol secretion estimated by area under the curve was lower (F((3,33))=4.602, p=0.008) compared to the beginning and end of the course. Surprisingly self-reported stress, arousal and fatigue did not differ significantly across weeks, despite the large dropout rate (40%) and self-evident pressures of the course. We conclude that when controlling for many confounding variables, including participant adherence, post-awakening cortisol levels are sensitive to stressful challenge over a period of weeks.


Enantioselective synthesis of Garner's aldehyde by asymmetric hydroformylation.
Both enantiomers of Garner's aldehyde (3) are prepared from the same alkene 4 by catalytic asymmetric hydroformylation.


Catheter ablation of repetitive monomorphic ventricular tachycardia from left ventricular outflow tract guided by unipolar mapping.
Repetitive monomorphic ventricular tachycardia from the left ventricular outflow tract is an uncommon arrhythmia. Successful catheter ablation has been previously reported in a few cases, but a large number of applications were usually needed when an approach based on either activation mapping or pace mapping was used. In our patient, the selection of the target point for application was based exclusively on unipolar mapping criteria of the ectopic beats, resulting in a short procedure with successful outcome.


Impact of genetic variants within serotonin turnover enzymes on human cerebral monoamine oxidase A in vivo.
Variants within the monoamine oxidase A (MAO-A, MAOA) and tryptophan hydroxylase 2 (TPH2) genes, the main enzymes in cerebral serotonin (5-HT) turnover, affect risk for depression. Depressed cohorts show increased cerebral MAO-A in positron emission tomography (PET) studies. TPH2 polymorphisms might also influence brain MAO-A because availability of substrates (i.e. monoamine concentrations) were shown to affect MAO-A levels. We assessed the effect of MAOA (rs1137070, rs2064070, rs6323) and TPH2 (rs1386494, rs4570625) variants associated with risk for depression and related clinical phenomena on global MAO-A distribution volume (VT) using [11C]harmine PET in 51 participants (21 individuals with seasonal affective disorder (SAD) and 30 healthy individuals (HI)). Statistical analyses comprised general linear models with global MAO-A VT as dependent variable, genotype as independent variable and age, sex, group (individuals with SAD, HI) and season as covariates. rs1386494 genotype significantly affected global MAO-A VT after correction for age, group and sex (p < 0.05, corr.), with CC homozygotes showing 26% higher MAO-A levels. The role of rs1386494 on TPH2 function or expression is poorly understood. Our results suggest rs1386494 might have an effect on either, assuming that TPH2 and MAO-A levels are linked by their common product/substrate, 5-HT. Alternatively, rs1386494 might influence MAO-A levels via another mechanism, such as co-inheritance of other genetic variants. Our results provide insight into how genetic variants within serotonin turnover translate to the cerebral serotonin system. Clinicaltrials.gov Identifier: NCT02582398. EUDAMED Number: CIV-AT-13-01-009583.


Haemophilus influenzae septicaemia and urinary tract infection associated with nefrocalcinosis: case report.
Haemophilus influenzae is an uncommon uropathogen with fastidious growth requirements, which must be taken into consideration in the diagnostic process. We present a rare case of urosepsis with H. influenzae in a young patient with nefrocalcinosis.


The pathologic characteristics of breast cancer in China and its shift during 1999-2008: a national-wide multicenter cross-sectional image over 10 years.
In China, breast cancer is currently the most common malignancy and the sixth leading cause of cancer death in women. But, the characteristics of breast cancer in the whole population are not determined. The aim of this study was to perform a detailed study on pathologic characteristics of breast cancer representing the whole population in China during 1999-2008 and to compare the difference in invasive breast cancer between the Western and Chinese. We randomly collected 4,211 inpatient at seven hospitals in representative geographical regions of China during 1999-2008. All the hospitals had the ability of comprehensive cancer treatment. The pathologic characters including estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status were surveyed. The shift of pathologic characters was evaluated and the data from China were also compared with those of the Western, both using Chi-square test. We found as follow. (i) The median age of the patients was 48 years and showed the similar characters of Asia. (ii) Breast cancer in China showed more invasive ductal carcinoma with larger tumor size, later stage, lower ER and PR expression and higher HER2 overexpression than those in the Western (p < 0.001). (iii) Both tumor size and stage at diagnosis decreased year by year (p < 0.001). Breast cancer in China showed more aggressive behavior than those in western countries, although tumor size and stage at diagnosis decreased by year during 1999-2008. We addressed the urgent needs for employ race-specific breast cancer screen, diagnosis methods, and therapeutic models in China.


Role of plasminogen activator inhibitor-1 in glucocorticoid-induced muscle change in mice.
We recently revealed that plasminogen activator inhibitor-1 (PAI-1), a serine protease inhibitor, is involved in diabetes, osteoporosis and muscle wasting induced by glucocorticoid (GC) treatment in mice. In the present study, we investigated the detailed mechanisms by which GC induces muscle wasting through PAI-1 in vivo and in vitro. PAI-1 deficiency suppressed the mRNA levels of atrogin1 and muscle RING-Finger Protein 1 (MuRF1), ubiquitin ligases leading to muscle degradation, elevated by GC treatment in the gastrocnemius muscle of mice. In vitro study revealed that active PAI-1 treatment augmented the increase in atrogin1 mRNA levels enhanced by dexamethasone (Dex) in mouse myoblastic C2C12 cells. Moreover, a reduction in endogenous PAI-1 level by siRNA suppressed the mRNA levels of atrogin1 and MuRF1 enhanced by Dex in C2C12 cells. In contrast, a reduction in endogenous PAI-1 levels and active PAI-1 did not affect the phosphorylations of Akt and p70S6 kinase nor myogenic differentiation with or without Dex in C2C12 cells. In addition, PAI-1 deficiency blunted IGF-1 mRNA levels decreased by GC treatment in the gastrocnemius muscle of mice, although neither active PAI-1 nor a reduction in endogenous PAI-1 levels affected the levels of IGF-1 mRNA in C2C12 cells in the presence of Dex. In conclusion, our data suggest that paracrine PAI-1 is involved in GC-induced muscle wasting through the enhancement of muscle degradation in mice.


Cycloheximide prevents apomorphine-induced yawning, penile erection and genital grooming in rats.
Apomorphine (50 micrograms/kg) induced repeated episodes of yawning, penile erection and genital grooming in rats. A dose of cycloheximide, which inhibited brain protein synthesis by 50% totally prevented apomorphine-induced yawning and reduced by approximately 50% the occurrence of episodes of penile erection and genital grooming. However, this treatment failed to modify the stereotyped behaviour induced by 200 micrograms/kg of apomorphine. These results suggest that protein synthesis is required for the behavioural effects of small doses of apomorphine.


Physical basis for long-distance communication along meiotic chromosomes.
Viable gamete formation requires segregation of homologous chromosomes connected, in most species, by cross-overs. DNA double-strand break (DSB) formation and the resulting cross-overs are regulated at multiple levels to prevent overabundance along chromosomes. Meiotic cells coordinate these events between distant sites, but the physical basis of long-distance chromosomal communication has been unknown. We show that DSB hotspots up to ∼200 kb (∼35 cM) apart form clusters via hotspot-binding proteins Rec25 and Rec27 in fission yeast. Clustering coincides with hotspot competition and interference over similar distances. Without Tel1 (an ATM tumor-suppressor homolog), DSB and crossover interference become negative, reflecting coordinated action along a chromosome. These results indicate that DSB hotspots within a limited chromosomal region and bound by their protein determinants form a clustered structure that, via Tel1, allows only one DSB per region. Such a "roulette" process within clusters explains the observed pattern of crossover interference in fission yeast. Key structural and regulatory components of clusters are phylogenetically conserved, suggesting conservation of this vital regulation. Based on these observations, we propose a model and discuss variations in which clustering and competition between DSB sites leads to DSB interference and in turn produces crossover interference.


Diagnostic utility of the dexamethasone suppression test.
This article discusses the current controversy surrounding the diagnostic utility of the Dexamethasone Suppression Test, addresses the questions raised by the recent editorial by Ross in this journal, discusses the general principles behind the development of tests, and estimates their diagnostic utility. This discussion aims to clarify some aspects of the controversy. It presents an operational analysis of the Dexamethasone Suppression Test as utilized at a state hospital. This operational analysis shows that the test may be useful in distinguishing schizophrenia from psychotic depression, and mania from schizophrenia. Furthermore, it shows that the test is not useful as a screening test. These results are compared with those obtained by other investigators. The authors further show how test results can be used rationally by clinicians by so-called threshold analysis. Clinical data from a state hospital are used to illustrate this.


The impact of a context switch and context instructions on the return of verbally conditioned fear.
Repeated exposure to a conditioned stimulus can lead to a reduction of conditioned fear responses towards this stimulus (i.e., extinction). However, this reduction is often fragile and sensitive to contextual changes. In the current study, we investigated whether extinction of fear responses established through verbal threat instructions is also sensitive to contextual changes. We additionally examined whether verbal instructions can strengthen the effects of a context change. Fifty-two participants were informed that one colored rectangle would be predictive of an electrocutaneous stimulus, while another colored rectangle was instructed to be safe. Half of these participants were additionally informed that this contingency would only hold when the background of the computer screen had a particular color but not when it had another color. After these instructions, the participants went through an unannounced extinction phase that was followed by a context switch. Results indicate that extinguished verbally conditioned fear responses can return after a context switch, although only as indexed by self-reported expectancy ratings. This effect was stronger when participants were told that CS-US contingency would depend on the background color, in which case a return of fear was also observed on physiological measures of fear. Extinction was not very pronounced in this study, possibly limiting the extent to which return of fear could be observed on physiological measures. Contextual cues can impact the return of fear established via verbal instructions. Verbal instructions can further strengthen the contextual control of fear.


Gamma Knife stereotactic radiosurgery for cerebellopontine angle meningioma.
Meningiomas comprise 6-15 % of cerebellopontine angle (CPA) tumors. Surgical treatment is a real challenge because this area is occupied by several critical neurovascular elements. Currently, surgery is the first choice of treatment, however several factors may be present that necessitate choosing the alternative treatments such as Gamma Knife Stereotactic Radiosurgery (GKS). Ninety-three patients with CPA meningioma who were treated by GKS for a period of 8 years, were retrospectively reviewed. Factors affecting clinical and radiological improvement were analyzed. The median tumor volume was 6 cm3. The mean values for maximal and marginal dose were 20.2 and 13.6 Gy, respectively. The mean follow-up time was 31.5 months. Tumor control (lack of progression) was achieved in 96.8% of the patients and 55.9% of the patients showed tumor regression on follow-up MRI. The actuarial 3-year progression-free survival (PFS) rate was 96%. Clinical improvement was seen in 49.5% of the patients while 11.8% experienced worsening or new-onset symptoms. Adverse radiation effects were seen in 4.3% of the patients. A worse symptomatic outcome, male sex, a lower tumor coverage, and marginal doses <13.5 Gy were associated with worse radiologic outcomes. Worse radiologic outcomes and higher tumor volumes, especially tumor volumes ≥8.5 cc, were associated with worse symptomatic outcomes. The male sex was associated with a lower PFS. Gamma Knife radiosurgery, either primarily or post- operatively, offers a decent long-term tumor control in CPA meningioma, and is associated with an acceptable complication profile, especially in tumors with lower volumes.


Degradation of mineral-immobilized pyrene by ferrate oxidation: Role of mineral type and intermediate oxidative iron species.
Ferrate (Fe(VI)) salts like K2FeO4 are efficient green oxidants to remediate organic contaminants in water treatment. Minerals are efficient sorbents of contaminants and also excellent solid heterogeneous catalysts which might affect Fe(VI) remediation processes. By targeting the typical polycyclic aromatic hydrocarbon compound - pyrene, the application of Fe(VI) for oxidation of pyrene immobilized on three minerals, i.e., montmorillonite, kaolinite and goethite was studied for the first time. Pyrene immobilized on the three minerals was efficiently oxidized by Fe(VI), with 87%-99% of pyrene (10 μM) being degraded at pH 9.0 in the presence of a 50-fold molar excess Fe(VI). Different minerals favored different pH optima for pyrene degradation, with pH optima from neutral to alkaline following the order of montmorillonite (pH 7.0), kaolinite (pH 8.0), and goethite (pH 9.0). Although goethite revealed the highest catalytic activity on pyrene degradation by Fe(VI), the greater noneffective loss of the oxidative species by ready self-decay in the goethite system resulted in lower degradation efficiency compared to montmorillonite. Protonation and Lewis acid on montmorillonite and goethite assisted Fe(VI) oxidation of pyrene. The intermediate ferrate species (Fe(V)/Fe(IV)) were the dominant oxidative species accountable for pyrene oxidation, while the contribution of Fe(VI) species was negligible. Hydroxyl radical was involved in mineral-immobilized pyrene degradation and contributed to 11.5%-27.4% of the pyrene degradation in montmorillonite system, followed by kaolinite (10.8%-21.4%) and goethite (5.1%-12.2%) according to the hydroxyl radical quenching experiments. Cations abundant in the matrix and dissolved humic acid hampered pyrene degradation. Finally, two different degradation pathways both producing phthalic acid were identified. This study demonstrates efficient Fe(VI) oxidation of pyrene immobilized on minerals and contributes to the development of efficient environmentally friendly Fe(VI) based remediation techniques.


Brain mechanisms that underlie the effects of motivational audiovisual stimuli on psychophysiological responses during exercise.
Motivational audiovisual stimuli such as music and video have been widely used in the realm of exercise and sport as a means by which to increase situational motivation and enhance performance. The present study addressed the mechanisms that underlie the effects of motivational stimuli on psychophysiological responses and exercise performance. Twenty-two participants completed fatiguing isometric handgrip-squeezing tasks under two experimental conditions (motivational audiovisual condition and neutral audiovisual condition) and a control condition. Electrical activity in the brain and working muscles was analyzed by use of electroencephalography and electromyography, respectively. Participants were asked to squeeze the dynamometer maximally for 30s. A single-item motivation scale was administered after each squeeze. Results indicated that task performance and situational motivational were superior under the influence of motivational stimuli when compared to the other two conditions (~20% and ~25%, respectively). The motivational stimulus downregulated the predominance of low-frequency waves (theta) in the right frontal regions of the cortex (F8), and upregulated high-frequency waves (beta) in the central areas (C3 and C4). It is suggested that motivational sensory cues serve to readjust electrical activity in the brain; a mechanism by which the detrimental effects of fatigue on the efferent control of working muscles is ameliorated.


Probability density function for random photon steps in a binary (isotropic-Poisson) statistical mixture.
Monte Carlo (MC) simulations allowing to describe photons propagation in statistical mixtures represent an interest that goes way beyond the domain of optics, and can cover, e.g., nuclear reactor physics, image analysis or life science just to name a few. MC simulations are considered a "gold standard" because they give exact solutions (in the statistical sense), however, in the case of statistical mixtures their implementation is often extremely complex. For this reason, the aim of the present contribution is to propose a new approach that should allow us in the future to simplify the MC approach. This is done through an explanatory example, i.e.; by deriving the 'exact' analytical expression for the probability density function of photons' random steps (single step function, SSF) propagating in a medium represented as a binary (isotropic-Poisson) statistical mixture. The use of the SSF reduces the problem to an 'equivalent' homogeneous medium behaving exactly as the original binary statistical mixture. This will reduce hundreds MC simulations, allowing to obtain one set of wanted parameters, to only one equivalent simple MC simulation. To the best of our knowledge the analytically 'exact' SSF for a binary (isotropic-Poisson) statistical mixture has never been derived before.


BRCA1 185delAG Mutation Enhances Interleukin-1β Expression in Ovarian Surface Epithelial Cells.
Familial history remains the strongest risk factor for developing ovarian cancer (OC) and is associated with germline BRCA1 mutations, such as the 185delAG founder mutation. We sought to determine whether normal human ovarian surface epithelial (OSE) cells expressing the BRCA1 185delAG mutant, BRAT, could promote an inflammatory phenotype by investigating its impact on expression of the proinflammatory cytokine, Interleukin-1β (IL-1β). Cultured OSE cells with and without BRAT were analyzed for differential target gene expression by real-time PCR, western blot, ELISA, luciferase reporter, and siRNA assays. We found that BRAT cells expressed increased cellular and secreted levels of active IL-1β. BRAT-expressing OSE cells exhibited 3-fold enhanced IL-1β mRNA expression, transcriptionally regulated, in part, through CREB sites within the (-1800) to (-900) region of its promoter. In addition to transcriptional regulation, BRAT-mediated IL-1β expression appears dualistic through enhanced inflammasome-mediated caspase-1 cleavage and activation of IL-1β. Further investigation is warranted to elucidate the molecular mechanism(s) of BRAT-mediated IL-1β expression since increased IL-1β expression may represent an early step contributing to OC.


A Genetic Screen Links the Disease-Associated Nab2 RNA-Binding Protein to the Planar Cell Polarity Pathway in Drosophila melanogaster.
Mutations in the gene encoding the ubiquitously expressed RNA-binding protein ZC3H14 result in a non-syndromic form of autosomal recessive intellectual disability in humans. Studies in Drosophila have defined roles for the ZC3H14 ortholog, Nab2 (aka Drosophila Nab2 or dNab2), in axon guidance and memory due in part to interaction with a second RNA-binding protein, the fly Fragile X homolog Fmr1, and coregulation of shared Nab2-Fmr1 target mRNAs. Despite these advances, neurodevelopmental mechanisms that underlie defective axonogenesis in Nab2 mutants remain undefined. Nab2 null phenotypes in the brain mushroom bodies (MBs) resemble defects caused by alleles that disrupt the planar cell polarity (PCP) pathway, which regulates planar orientation of static and motile cells via a non-canonical arm of the Wnt/Wg pathway. A kinked bristle phenotype in surviving Nab2 mutant adults additionally suggests a defect in F-actin polymerization and bundling, a PCP-regulated processes. To test for Nab2-PCP genetic interactions, a collection of PCP mutant alleles was screened for modification of a rough-eye phenotype produced by Nab2 overexpression in the eye (GMR>Nab2) and, subsequently, for modification of a viability defect among Nab2 nulls. Multiple PCP alleles dominantly modify GMR>Nab2 eye roughening and a subset rescue low survival and thoracic bristle kinking in Nab2 zygotic nulls. Collectively, these genetic interactions identify the PCP pathway as a potential target of the Nab2 RNA-binding protein in developing eye and wing tissues and suggest that altered PCP signaling could contribute to neurological defects that result from loss of Drosophila Nab2 or its vertebrate ortholog ZC3H14.


Interrater reliability of an oral case presentation rating tool in a pediatric clerkship.
Composing and delivering effective oral case presentations is an important skill for medical students to learn, but the large variety of patients and presenting problems makes teaching and evaluating this skill complex. Few published tools are available for educators to use, and those that are described are not well studied. The authors describe the development of the Patient Presentation Rating tool and the study to establish its interrater reliability. Three raters reviewed 15 recorded new patient presentations delivered by 3rd-year medical students on their pediatrics clerkship. Intraclass correlation coefficients were used to determine the interrater reliability of the tool as a whole, its subsections, and each individual item. The tool was found to reliably rate the technical aspects of presenting patients as well as several aspects of clinical reasoning embedded in that process. The Patient Presentation Rating tool is a reliable instrument for evaluating medical students' oral patient presentations.


[Penile necrosis, a specific complication of prostatic artery embolization].
Endoscopic surgery is the standard treatment for benign prostatic hyperplasia (BPH) refractory to pharmacological treatments. In order to reduce invasiveness and preserve sexual function, prostatic artery embolization (PAE) has been developed. However, the technical difficulties of carrying out this procedure and the results, which have yet to be confirmed, mean that it is not currently recommended. The seriousness of the complications generated should lead to a reflection on the benefit-risk balance. The objective is to report a case of penile ischemia after embolization of the prostatic arteries. A severe complication following prostatic artery embolization (PAE) is reported with its clinical and paraclinical evaluation before and after the procedure as well as the therapeutic management. Penile necrosis following prostatic artery embolization was reported in a 75-year-old patient despite an attempt of deobstruction. Lower urinary tract symptoms worsened postoperatively, associated with glans necrosis and refractory erectile dysfunction. The place of PAE in the therapeutic arsenal of BPH needs to be confirmed. This innovative technique exposes the patient to potentially severe risks such as penile ischemia, not encountered in conventional endoscopic surgical treatment. PAE should not be included in the therapeutic armamentarium for BPH outside of clinical trials.


Screening for hyperlipoproteinemia in 10,000 Danish newborns. Follow-up studies in 522 children with elevated cord serum VLDL-LDL-cholesterol.
Among 10 440 newborns, 522 with upper 5 percentile values for very low-low density lipoprotein cholesterol in cord serum were selected for follow-up studies. Follow-up was possible in 446 of these 522 families (85%) and familial hypercholesterolemia (FH) was diagnosed in 11. In 273 of the 522 children, serum lipids were determined between the ages of 1 and 2 years and were now found to be normal, except in the 11 children with FH. Furthermore the serum lipids were compared in subgroups of these 273 children divided according to obstetric complications (i.e. low birth-weight, perinatal asphyxia and antepartum betamethasone treatment), which may cause a rise in serum lipids at birth. No differences were found between these subgroups at the age of 1--2 years.


[Endoscopic diagnosis, treatment, and follow-up of polyps of the upper gastrointestinal tract].
Polyps occur significantly less frequently in the upper gastrointestinal tract compared to the lower gastrointestinal tract. They are usually incidental findings at esophagogastroduodenoscopy. A distinction is made between epithelial lesions and subepithelial tumors. Endoscopic screening is not recommended in Germany (exception: hereditary risk groups). Polyps are sometimes symptomatic, generally in the case of advanced tumor size. In this case, or in the case of potential for malignant transformation, resection is necessary and can usually be performed endoscopically. Surgical resections are rarely necessary. Epithelial lesions are removed by means of endoscopic mucosal resection (EMR). For subepithelial tumors, advanced procedures such as endoscopic submucosal dissection (ESD), submucosal tunneling endoscopic resection (STER), or endoscopic full-thickness resection are available. These procedures should primarily be performed at centers with appropriate expertise. Endoscopic follow-up is primarily determined by the tumor entity and the resection status.


Utility of neuromuscular ultrasound in the investigation of common mononeuropathies in everyday neurophysiology practice.
In everyday clinical neurophysiology practice, mononeuropathies are evaluated primarily by traditional electrodiagnostic testing. We sought to assess the additional benefit of neuromuscular ultrasound (US) in this scenario. All consecutive mononeuropathies undergoing combined US and electrodiagnostic evaluation over a 23-mo period at a single neurophysiology practice were reviewed. Three independent examiners assessed how often US was: (a) "contributory" - enabling a definite diagnosis not made by electrophysiology alone and/or impacting on the therapeutic decision, (b) "confirmatory" of the electrodiagnostic findings, but not adding further diagnostic or therapeutic information, or (c) "negative" - missed the diagnosis. There were 385 studies included. US was "contributory" in 36%, "confirmatory" in 61% and "negative" in 3%. In this study of everyday neurophysiology practice, neuromuscular US contributed significant diagnostic or therapeutic information in over 1/3 of the investigations for common mononeuropathies. False negative US studies were uncommon in this setting.


The association between gestational weight gain and substantial weight retention 1-year postpartum.
Postpartum weight retention contributes to obesity development of women in their reproductive age. The studies about the association between gestational weight gain (GWG) and substantial weight retention are lacking. This study examined the association between GWG and substantial postpartum weight retention (SPPWR). The participants (n = 1,122) in the study were healthy, mature and fed their infants whose ages were 3, 6, 9, 12 months (2010-2012), respectively. They self-reported their socio-demographic, clinical prenatal and behaviors characteristics via questionnaires. We collected their weight data including pre-pregnancy and prior to delivery, as well as weight at 3, 6, 9, and 12 months postpartum. The major outcomes included weight retention and substantial weight gain 1 year postpartum. Of the 1,122 women, the median weight retention was 3.0 (IQR = 5.5) kg 12 months postpartum. 35.7 % of them reported substantial weight retention (≥4.55 kg). GWG categories were established as follows: inadequate weight gain (n = 366, 33 %), adequate weight gain (n = 596, 53 %), and excessive weight gain (n = 160, 14 %). Adjusted odds ratios of SPPWR were 0.59 (95 % CI 0.43, 0.81) for inadequate weight gain and 4.05 (95 % CI 2.75, 5.95) for excessive weight gain versus adequate weight gain (P < 0.001). Excessive GWG would increase the risk of substantial weight retention 1-year postpartum. The interventions to prevent postpartum obesity should consider the strategies how to attain optimal maternal GWG.


Genetic Constitution and Pathogenicity of Lolium Isolates of Magnaporthe oryzae in Comparison with Host Species-Specific Pathotypes of the Blast Fungus.
ABSTRACT Fungal isolates from gray leaf spot on perennial ryegrass (prg isolates) were characterized by DNA analyses, mating tests, and pathogenicity assays. All of the prg isolates were interfertile with Triticum isolates and clustered into the crop isolate group (CC group) on a dendrogram constructed from rDNA-internal transcribed spacer 2 sequences. Since the CC group corresponded to a newly proposed species, Magnaporthe oryzae, all of the prg isolates were designated M. oryzae. However, DNA fingerprinting with MGR586, MGR583, and Pot2 showed that the prg isolates are divided into two distinct populations, i.e., TALF isolates and WK isolates. The TALF isolates were virulent only on Lolium species, whereas the WK isolates were less specific, suggesting that gray leaf spot can be caused not only by Lolium-specific isolates but also by less specific isolates. We designated the TALF isolates as Lolium pathotype. The TALF isolates showed diverse karyotypes in spite of being uniform in DNA fingerprints, suggesting that theyare unstable in genome organization.


Early ophthalmologic features of Parkinson's disease: a review of preceding clinical and diagnostic markers.
Non-motor symptoms in Parkinson's disease are an important cause of morbidity and may even precede the onset of the motor features of the disease. Visual abnormalities are among the most frequent non-motor symptoms observed during the early stages of the disease. Some of the visual symptoms of Parkinson's disease can likely be explained by the presence of dopaminergic neurons within the retina, where the progressive loss of dopamine and the accumulation of α-synuclein within the retinal layers leads to visual dysfunction, while some are caused by abnormalities in cortical visual processing. Many of these visual symptoms can be overlooked or go unrecognized. We review the visual symptoms in Parkinson's disease, including visual-processing and ocular motility abnormalities, stereopsis deficits, and visual hallucinations, focusing on the early stages of the disease. We focus on the reciprocal influence between the visual symptoms and the progression of the disease, analyzing the influence of dopaminergic therapy on the visual abnormalities. Finally, we discuss the possible role of some of these visual symptoms as possible markers or early diagnostic signs of the disease.


Diagnosis and Management of Monogenic Diabetes in Pregnancy.
Monogenic diabetes occurs in up to 3% of people with diabetes. Mutations in over 40 different genes are responsible. The most common genes affected are HNF1A, HNF4A, GCK, and HNF1B. Additionally, other types of diabetes with a genetic aetiology include neonatal diabetes and diabetes plus syndrome. Each of these genetic subtypes has a different phenotype and requires distinctive treatments. Due to the overlap of monogenic diabetes with type 1 and 2 diabetes and even gestational diabetes, they can often be misdiagnosed. During pregnancy, individual subtypes require treatment that is different from standard diabetes care, so recognition and prompt diagnosis of monogenic diabetes are important to avoid inadequate treatment. We describe the management of monogenic diabetes for the most significant subtypes, focussing on the impact on and management in pregnancy. A genetic diagnosis of diabetes can alter long-term treatment in those with diabetes. In pregnancy and the postnatal period, this can involve specific management changes determined by the gene affected and whether there is a fetal inheritance of the gene. Where inheritance of the genotype influences the outcomes, cell-free fetal testing will hopefully soon become a diagnostic tool for early recognition of fetal mutations.


Optimized risk stratification strategy for glioma patients based on the feature genes of poor immune cell infiltration patterns.
Gliomas, originating from glial cells within the brain or spinal cord, are common central nervous system tumors with varying degrees of malignancy that influence the complexity and difficulty of treatment. The current strategies, including traditional surgery, radiotherapy, chemotherapy, and emerging immunotherapies, have yielded limited results. As such, our study aims to optimize risk stratification for a more precise treatment approach. We primarily identify feature genes associated with poor immune cell infiltration patterns through various omics algorithms and categorize glioma patients based on these genes to enhance the accuracy of patient prognosis assessment. This approach can underpin individualized treatment strategies and facilitate the discovery of new therapeutic targets. We procured datasets of gliomas and normal brain tissues from TCGA, CGGA, and GTEx databases. Clustering was conducted using the input of 287 immune cell feature genes. Hub genes linked with the poor prognosis subtype (C1) were filtered through WGCNA. The TCGA dataset served as the discovery cohort and the CGGA dataset as the external validation cohort. We constructed a prognostic model related to feature genes from poor immune cell infiltration patterns utilizing LASSO-Cox regression. Comprehensive analyses of genomic heterogeneity, tumor stemness, pathway relevance, immune infiltration patterns, treatment response, and potential drugs were conducted for different risk groups. Gene expression validation was performed using immunohistochemistry (IHC) on 98 glioma samples and 11 normal brain tissue samples. Using the filtered immune cell-related genes, glioma patients were stratified into C1 and C2 subtypes through clustering. The C1 subtype exhibited a worse prognosis, with upregulated genes primarily enriched in immune response, extracellular matrix, etc., and downregulated genes predominantly enriched in neural signal transduction and neural pathway-related aspects. Seven advanced algorithms were used to elucidate immune cell infiltration patterns of different subtypes. In addition, WGCNA identified hub genes from poor immune infiltration patterns, and a prognostic model was constructed accordingly. High-risk patients demonstrated shorter survival times and higher risk scores as compared to low-risk patients. Multivariate Cox regression analysis revealed that, after adjusting for confounding clinical factors, risk score was a vital independent predictor of overall survival (OS) (P < 0.001). The established nomogram, which combined risk scores with WHO grade and age, accurately predicted glioma patient survival rates at 1, 3, and 5 years, with AUCs of 0.908, 0.890, and 0.812, respectively. This risk score enhanced the nomogram's reliability and informed clinical decision-making. We also comprehensively analyzed genomic heterogeneity, tumor stemness, pathway relevance, immune infiltration patterns, treatment response, and potential drugs for different risk groups. In addition, we conducted preliminary validation of the potential PLSCR1 gene using IHC with a large sample of gliomas and normal brain tissues. Our optimized risk stratification strategy for glioma patients has the potential to improve the accuracy of prognosis assessment. The findings from our omics research not only enhance the understanding of the functions of feature genes related to poor immune cell infiltration patterns but also offer valuable insights for the study of glioma prognostic biomarkers and the development of individualized treatment strategies.


Di-2-pyridylketone-N1-substituted thiosemicarbazone derivatives of copper(II): Biosafe antimicrobial potential and high anticancer activity against immortalized L6 rat skeletal muscle cells.
The basic aim of this study pertains to developing antimicrobial or anticancer agents based on N, S-donor organic ligands bonded to metals. In the present investigation, di-2-pyridylketone-N1-substituted thiosemicarbazone (py2tscH-N1HR2, Chart 2) thio-ligands were reacted with copper(I) halides in organic solvents yielding copper(II) complexes of stoichiometry, [Cu(N,N,S-py2tsc-N1HR2)X] (X = I, R2 = H, 1; Me, 2; Et, 3; Ph, 4; X = Br, R2 = H, 5; Me, 6; Et, 7; Ph, 8; X = Cl, R2 = H, 9; Me, 10; Et, 11; Ph, 12); the formation of CuII probably occurs through a proton coupled electron transfer (PCET) process. Electron spin resonance, ultraviolet-visible spectroscopy and X-ray crystallography (2, 3, 5, 7, 11) supported a distorted square planar geometry of these complexes. Moderate to high antimicrobial activities of these complexes against methicillin resistant Staphylococcus aureus, Gram positive bacteria, Staphylococcus aureus and Gram negative bacteria, Klebsiella pneumoniae 1, Salmonella typhimurium 2 and one yeast Candida albicans were recorded. Complexes were found to be biosafe with 88-91% cellular viability. All complexes have shown high anticancer activity against the immortalized L6 rat skeletal muscle cell line with very low IC50 values.


Weekly pulse therapy of methotrexate improves survival compared with its daily administration in MRL/lpr mice.
The purpose of this study was to determine whether weekly pulse therapy was superior to daily administration of methotrexate in MRL/lpr mice. Oral methotrexate was given to 6-week-old MRL/lpr mice at doses of 0.3, 1.0, or 3.0 mg/kg 5 days a week or at a dose of 15.0 mg/kg once a week until 35 weeks of age. The effects of methotrexate on physical, serological, and pathological findings were assessed. The survival rate and articular destruction on X-ray films were also evaluated. Both weekly pulse therapy and daily administration of methotrexate at the same weekly dose improved nephropathy and articular destruction of MRL/lpr mice when compared with control. However, weekly pulse therapy with methotrexate prolonged the survival of MRL/lpr mice when compared with the daily administration of the same weekly dose of methotrexate and control. Methotrexate did not suppress the increase in anti-DNA antibody and rheumatoid factor. Daily administration of methotrexate reduced the red and white blood cell counts, whereas weekly pulse therapy caused little reduction. In conclusion, weekly pulse therapy was superior to daily administration of methotrexate with respect to the survival rate, possibly due to a reduction in toxicity.


Smoking related cancers and loci at chromosomes 15q25, 5p15, 6p22.1 and 6p21.33 in the Polish population.
Genetic factors associated with the risk of smoking related cancers have until recently remained elusive. Since the publication of a genome-wide association study (GWAS) on lung cancer new genetic loci have been identified that appear to be associated with disease risk. In this replication study we genotyped 14 single nucleotide polymorphisms (SNPs) located at the 5p12.3-p15.33, 6p21.3-p22.1, 6q23-q27 and 15q25.1 loci in 874 lung, 450 bladder, 418 laryngeal cancer cases and cancer-free controls, matched by year of birth and sex to the cases. Our results revealed that loci in the chromosome region 15q25.1 (rs16969968[A], rs8034191[G]) and 5p15 (rs402710[T]) are associated with lung cancer risk in the Polish population (smoking status adjusted OR = 1.45, 1.35, 0.77; p ≤ 0.0001, 0.0005, 0.002; 95%CI 1.23-1.72, 1.14-1.59, 0.66-0.91 respectively). None of the other regions analyzed herein were implicated in the risk of lung, bladder or laryngeal cancer. This study supports previous findings on lung cancer but fails to show association of SNPs located in 15q25.1 and 5p15 region with other smoking related cancers like bladder and laryngeal cancer.


Tailored Multivalent Targeting of Siglecs with Photosensitizing Liposome Nanocarriers.
The modification of surfaces with multiple ligands allows the formation of platforms for the study of multivalency in diverse processes. Herein we use this approach for the implementation of a photosensitizer (PS)-nanocarrier system that binds efficiently to siglec-10, a member of the CD33 family of siglecs (sialic acid (SA)-binding immunoglobulin-like lectins). In particular, a zinc phthalocyanine derivative bearing three SA moieties (PcSA) has been incorporated in the membrane of small unilamellar vesicles (SUVs), retaining its photophysical properties upon insertion into the SUV's membrane. The interaction of these biohybrid systems with human siglec-10-displaying supported lipid bilayers (SLBs) has shown the occurrence of weakly multivalent, superselective interactions between vesicle and SLB. The SLB therefore acts as an excellent cell membrane mimic, while the binding with PS-loaded SUVs shows the potential for targeting siglec-expressing cells with photosensitizing nanocarriers.


Discussion of "The Asymmetric Impact of COVID-19: A Novel Approach to Quantifying Financial Distress across Industries".
The COVID-19 pandemic crisis and the associated lockdown measures have exerted significantly adverse effects on corporate sectors globally. Archanskaia et al. (2023) provide a novel empirical strategy to timely assess corporate financial distress in the EU. The contribution is two-fold. First, this paper's notion of financial distress considers both the equity position and corporate indebtedness. Second, the methodology proposed in this paper allows the authors to estimate corporate financial distress in the EU at a highly granular level and link micro-level simulations to sectoral macroeconomic outcomes. The methodology employed by Archanskaia et al. (2023) consists of three steps. First, the authors apply a nowcasting model to acquire monthly industrial turnover data. Second, they feed the obtained monthly industrial turnover into a profit-generating process via an accounting identity to estimate monthly firm profits at the firm level. Third, the authors use the estimated firm profits with a snapshot of information on pre-existing liquid assets to deduce the firm-level liquidity needs and the depletion of equity through the focus period during COVID-19. These estimated results on firm equity position and indebtedness enable the authors to quantity corporate financial distress in the EU via various angles (e.g., country-level heterogeneity, industry heterogeneity, and the targeting of COVID support policies). The primary advantage of this approach is that it deals with large datasets at the granular level and produces firm-level results almost in real-time. Therefore, it can help policymaking track the effects of crises over time. However, one can quickly critique this three-step approach for its susceptibility to the usual Lucas critique. That said, since the objective here is to estimate firm-level financial distress, a large structural model being more or less aggregate in nature, though able to mitigate the Lucas critique concern, will encounter significant challenges in estimating firm-level results with the requisite level of granularity offered by the available data. Therefore, I broadly concur with the authors' position that 'the specific contribution of this paper consists in striking a better balance between the need to carry out a multi-country evaluation of the pandemic's effects on industrial activity in a strongly integrated region like the EU and the difficulty of capturing time, industry, and country variation in turnover with sufficient granularity.'


Lipoprotein composition in diabetes mellitus.
Lipoprotein cholesterol and triglyceride levels have been determined in normal and diabetic Pima Indian women aged 20-35, HDL cholesterol levels were lower, LDL cholesterol levels were higher, and the ratio of HDL cholesterol/LDL cholesterol, a reflection of lipoprotein cholesterol distribution, was lower in the diabetics compared to the normals. VLDL triglyceride levels were also elevated in the diabetics. An analysis of lipoprotein composition suggested that these changes primarily reflect changes in numbers of particles, since lipid composition and lipid/protein ratios were similar in lipoproteins isolated from normals and diabetics. The ratio of ester/free cholesterol in LDL and HDL was lower in normal Pima Indians than in a comparable group of Caucasians, although plasma LCAT activity was not significantly different. The data indicate that diabetes may be associated with shifts in distribution of LDL and HDL, as well as with increases in VLDL.


Genetic predisposition of variants in TLR2 and its co-receptors to severe malaria in Odisha, India.
Although the role of TLRs signalling in malaria pathogenesis is well established, contribution of individual TLR to clinical outcome of malaria still remains inconclusive. Given the importance of TLR2 and its co-receptors in recognising distinct structural forms of key malaria toxins and mediating innate immune response, it is essential to delineate their genetic contribution. Variants in TLR1 (I602S) and TLR6 (P249S) were genotyped by PCR-RFLP methods, and TLR2 (I/D) was genotyped by PCR in 200 samples each from uncomplicated malaria (UM) and severe malaria (SM). Further, SM was categorised into its sub-clinical groups (CM and NCSM or SOD and MODS) and analysed. The results showed the PP genotype of TLR6 (P249S) to be significantly more common in UM (P < 0.0001), whereas the 'SS' genotype was the risk factor for SM including its sub-clinical categories. The TLR1 (602S) and TLR2 (D) variants were significantly high in patients with CM; however, negative LD was observed between TLR2 and TLR6 in NCSM and MODS. Haplotype analysis showed significantly high frequency of I-I-S haplotype in all forms of subclinical SM and was associated with low parasite load in SM (P = 0.013). The haplotypes I-D-S and S-I-P were significantly high in SOD and CM, respectively. The TLR6 '249S' variant appeared to be the dominant determinant for genetic predisposition to SM and that its association with either TLR2 'D' or TLR1 '602S' modulates for CM development. The present study opens up several new avenues for their exploration and validation in future studies in different global settings for malaria.


Sensitive detection of aflatoxin B1 in foods by aptasensing-based qPCR.
In this study, a reproductive switch DNA template was designed using aptasensing principles for the accurate quantification of aflatoxins. The template transformed the aflatoxin molecule into linear DNA of 102 nt. The linear DNA was subjected to a quantitative polymerase chain reaction (qPCR) to determine its initial copy number, which was positively correlated with the aflatoxin concentration. Using aflatoxin B1 (AFB1) as a model, the established method could quantify AFB1 within the range of 10-16-10-11 Mol/mL (detection limit equals 0.03 pg/mL), with a linear correlation coefficient R2 of 0.974. Good anti-interference abilities against common food ingredients and high specificity towards other mycotoxins were demonstrated. The established method was successfully applied for the quantification of AFB1 in complex foods such as soy sauce, milk, yellow wine, and peanut butter. The design of a reproductive switch template introduces a novel approach for the sensitive detection of small-molecule toxicants in foods.


Effects of untreated bed nets on the transmission of Plasmodium falciparum, P. vivax and Wuchereria bancrofti in Papua New Guinea.
The impact of untreated bed nets on the transmission of human malaria and filariasis in a village in a hyperendemic area of Papua New Guinea was studied. In anopheline mosquitoes, the Plasmodium falciparum sporozoite antigen positivity rate, filarial infection rates and human blood indices dropped significantly after bed nets were introduced. This reduction in human-vector contact did not affect mosquito density as no significant difference in either landing rates or indoor resting catches was found. The number of bed nets in a house and ownership of dogs were factors significantly associated with a reduction in the number of indoor resting mosquitoes. However, the reduction in the P. falciparum sporozoite antigen rate in mosquitoes was not accompanied by a reduction in either malaria parasite or antibody prevalences or titres against the P. falciparum circumsporozoite protein.


[Male sex pheromones of noctuides (author's transl)].
By gaschromatographic-mass spectrometric methods 2-phenylethyl alcohol, benzylalcohol, phenylacetaldehyde and benzaldehyde were identified from scent brushes of male Noctuidae species (Lepidoptera).


Plasma aldosterone levels and aldosterone-to-renin ratios are associated with endothelial dysfunction in young to middle-aged subjects.
Small clinical studies suggested a role for aldosterone in the development of endothelial dysfunction. We investigated whether the plasma aldosterone concentration (PAC) or the aldosterone-to-renin ratio (ARR) were associated with decreased endothelial function as measured by flow-mediated dilation (FMD) of the brachial artery in the general population. Our study population comprised 972 participants from the Study of Health in Pomerania, who were not treated with antihypertensive medication. We performed age-stratified (<50 and ≥ 50 years) ordinal logistic regression analyses. FMD was categorised as decreased (1st quintile), moderate (2nd-4th quintile), or increased (5th quintile). PAC and ARR were divided into low, moderate, and high values according to age- and sex-specific tertiles. All models were re-calculated for 871 subjects with PAC and ARR within the study-specific reference ranges. Odds ratios (OR) and 95% confidence intervals (CI) are presented. Subjects <50 years with high PAC (OR 1.60; 95% CI 1.07-2.38) or ARR (OR 1.81; 95% CI 1.21-2.73) had higher odds for decreased FMD than subjects with low PAC or ARR, respectively. Similar results were obtained in analyses restricted to subjects with PAC and ARR within the reference range. High-normal PAC (OR 1.62; 95% CI 1.07-2.47) or ARR (OR 1.62; 95% CI 1.05-2.50) was associated with higher odds for decreased FMD when compared with low-normal PAC or ARR, respectively. These associations were not observed in subjects ≥ 50 years. High and high-normal PAC or ARR contribute to an impaired FMD and subsequently the progression of subclinical atherosclerosis in young to middle-aged subjects.


Pioglitazone protects against thrombosis in a mouse model of obesity and insulin resistance.
As arterial thrombosis accounts for the vast majority of cardiovascular complications in obese, insulin resistant patients, we hypothesized that improving insulin sensitivity may be effective in reducing the thrombotic response following vascular injury. We investigated the effect of the thiazolidinedione drug, pioglitazone, on the thrombotic response to injury in obese, insulin resistant mice. Insulin-resistant, obesity-prone mice (KK strain) were treated with pioglitazone, placebo, or the sulfonylurea compound, glipizide, for 2.5 weeks and then subjected to photochemical injury of the carotid artery. KK mice have a significant increase in adiposity (7 weeks: 25.6%; 15 weeks: 34.4%; P < 0.0001) and thrombotic tendency (7 weeks: 21.2 +/- 1.9 min; 15 weeks: 13.7 +/- 1.7 min; P < 0.01) with age. Pioglitazone provided significant protection from thrombosis at both time points, prolonging the time to occlusive thrombosis by 40% and 68%, at 7 and 15 weeks of age, respectively (P < 0.05). Similarly, following a diet-challenge to promote diabetes, pioglitazone provided protection from occlusive thrombus formation (Placebo: 11.3 +/- 1.0 min; Pioglitazone: 22.3 +/- 3.9 min; P < 0.05). However, despite a salient effect of glipizide on the hyperglycemia of the mice, there was no effect on the time to occlusive thrombus formation (13.2 +/- 0.9 min, n = 4) compared with placebo-treated mice. The pioglitazone protection was paralleled by significantly lower soluble P-selectin and platelet P-selectin expression providing evidence of an antiplatelet effect. We conclude that pioglitazone treatment provides protection against arterial thrombosis in an obese, insulin resistant, prothrombotic mouse model.


Pectoralis Major Myocutaneous Flap Reconstruction for the Mandibular Defects in Advanced Oral Cavity Malignancies: A Retrospective Study of 30 Cases.
To evaluate the utility of the pectoralis major myocutaneous (PMMC) flap for the reconstruction of the mandible in advanced oral cavity malignancies in the Indian population. It was a retrospective study contained 30 patients with advanced oral cancer from July 2012 to August 2016. The PMMC reconstruction was done in all the patients to repair the bony defects in segmental/hemi mandibulectomy. The patients were followed up for a mean period of 6 months in the postoperative period and the utility of the PMMC flaps were evaluated. The mean age of the patients was 45 years (range 30-63 years). The average Karnofsky performance status score was 70 and majority of the patients had history of chronic medical illness. Of the 30 PMMC flaps, partial necrosis of the skin was noticed 2 (06.66%) patients. Orocutaneous fistula was detected in 2 (06.66%) patient and 3 (10%) patients presented with wound dehiscent in the immediate postoperative period. 3 (10%) patients had recurrence of the disease. PMMC flap can be a reliable option for advanced oral malignancies, especially in patients with poor status with the coexisting chronic illness. Due to the presence of a definite vascular pedicle, ease of harvesting the flap, quick surgical procedure, and the minimal postoperative morbidities, it can be considered as a valid alternative to the free flap to repair the bony defect, especially in patients with low socioeconomic corridor like India.


Psychosis in Parkinson's disease: phenomenology, frequency, risk factors, and current understanding of pathophysiologic mechanisms.
Psychosis in Parkinson's disease refers to a combination of hallucinations and delusions occurring with a clear sensorium and a chronic course. Hallucinations may involve several sensory modalities. Complex visual hallucinations are the most common type. "Minor" hallucinatory phenomena are frequently present and include visual illusions, passage hallucinations, and sense of presence. Insight may be lost in patients with cognitive impairment. Delusions of a paranoid type are more rare than hallucinations. Both hallucinations and delusions are more frequent in Parkinson's disease patients with dementia. Pathogenesis involves complex and probably multifactorial mechanisms, including pharmacologic (dopaminergic treatment and others) and disease-related factors.


T-PALS framework to assess children who stutter with coexisting disorders: A tutorial.
The purpose of this paper is to present a tutorial on a diagnostic framework developed to assess children who stutter and exhibit co-existing disorders. While we have guidelines for treating these children, there are no specific guidelines for assessing them. We provide a rationale for the development of T-PALS with support from the literature. The T-PALS framework assesses 5 foundational key elements for the child: Temperament (T), Pragmatics (P), Articulation/phonology (A), Language (L), and Stuttering (S). Both qualitative and quantitative measures are used within each dimension. This framework is discussed with reference to using two clinical case examples. T-PALS observation data are presented as well as treatment suggestions for each case. We conclude that T-PALS may be a useful framework for both clinicians and researchers, working with children who present with stuttering and comorbid conditions. Clinicians are encouraged to reach beyond the traditional focus on solely assessing the stuttering behavior, even when that is the main concern for referral, and to consider a broader view of the child. It is hoped that this more integrative approach to assessment may yield a more holistic diagnostic picture of a dual diagnosis child from which treatment goals can be derived.


Stress distribution of single-implant-retained overdenture reinforced with a framework: A finite element analysis study.
Studies have demonstrated the effectiveness of a single-implant-retained mandibular overdenture for elderly patients with edentulism. However, due to the high concentration of stress around the housing portion of the single implant, this prosthesis tends to fracture at the anterior region more than the 2-implant-retained mandibular overdenture. The purpose of this finite-element analysis study was to evaluate the stress distribution in a single-implant-retained mandibular overdenture reinforced with a cobalt-chromium framework, to minimize the incidence of denture base fracture. Two 3-dimensional finite element models of mandibular overdentures supported by a single implant with a stud attachment were designed in SolidWorks 2013 software. The only difference between the models was the presence or absence of a cobalt-chromium framework at the denture base between canines. Subsequently, the models were imported into the mathematical analysis software ANSYS Workbench v15.0. A mesh was generated with an element size of 0.7 mm and submitted to convergence analysis before mechanical simulation. All materials were considered to be homogeneous, isotropic, and linearly elastic. A 100-N load was applied to the incisal edge of the central mandibular incisors at a 30-degree angle. Maximum principal stress was calculated for the overdenture, von Mises stress was calculated for the attachment and implant, and minimum principal stress was calculated for cortical and cancellous bone. In both models, peak stress on the overdenture was localized at the anterior intaglio surface region around the implant. However, the presence of the framework reduced the stress by almost 62% compared with the overdenture without a framework (8.7 MPa and 22.8 MPa, respectively). Both models exhibited similar stress values in the attachment, implant, and bone. A metal framework reinforcement for a single-implant-retained mandibular overdenture concentrates less stress through the anterior area of the prosthesis and could minimize the incidence of fracture.


The puzzle of intrafamilial child sexual abuse: a meta-analysis comparing intrafamilial and extrafamilial offenders with child victims.
Intrafamilial child sexual abuse is a serious social and health problem, yet explanations of sexual offending against children that emphasize antisocial tendencies and atypical sexual interests do not adequately explain intrafamilial offending. In this meta-analysis, we tested other explanations of intrafamilial child sexual abuse by examining 78 independent samples that compared a total of 6605 intrafamilial offenders to a total of 10,573 extrafamilial offenders, in studies disseminated between 1978 and 2013 (Mdn=2000). Intrafamilial offenders were significantly lower on variables reflecting antisocial tendencies (e.g., criminal history, juvenile delinquency, impulsivity, substance use, and psychopathy) and atypical sexual interests (e.g., pedophilia, other paraphilias, and excessive sexual preoccupation). Contrary to other explanations that have been proposed, intrafamilial offenders scored lower on offense-supportive attitudes and beliefs, emotional congruence with children, and interpersonal deficits; intrafamilial offenders also did not differ from extrafamilial offenders on most indicators of psychopathology. Intrafamilial offenders were, however, more likely to have experienced sexual abuse, family abuse or neglect, and poor parent-child attachments. There were too few studies to examine family dynamics - spousal relationship quality, parent-child victim relationship, and family functioning more generally - even though these factors have been frequently mentioned in the clinical and theoretical literatures. Implications for theories of intrafamilial sexual offending, treatment, and future directions for research are discussed.


Interaction of lipids with the plasma membrane of sperm cells. II. Evidence of a membrane thermotropic transition.
Cholesterol and phosphatidylcholine uptake from dipalmitoyl-phosphatidylcholine liposomes by rabbit spermatozoa showed a complex dependence on temperature in these experiments. At 5 degrees and 20 degrees C, the rate of lipid uptake correlated with temperature. However, from 20 degrees to 37 degrees C uptake did not evidently increased. The results in interpreted as evidence of a thermotropic transition in the sperm plasma membrane. Data are presented showing incorporation of these lipids, especially that of cholesterol, into sperm plasma membrane.


Rapid increase in copper concentrations in a new marina, San Diego Bay.
Concentrations of copper in water rose rapidly following the introduction of boats to a new marina in San Diego Bay. Two months after the marina reached half its capacity, a majority of water samples exceeded chronic and acute criteria for dissolved copper, and copper concentrations in several samples exceeded the highest concentrations observed in another marina that has been listed as an impaired water body. A box model suggested that a small fraction of the leached copper was sequestered in sediment. Copper concentrations in water entering the marina from the bay was more than half the chronic concentration limit, so only 50% of marina boat capacity could be accommodated without exceeding the chronic criterion more than 50% of the time. Copper concentrations in water may increase rapidly following boat introduction in small marinas, but could return to pre-introduction levels by controlling boat numbers or reducing use of copper-based paints.


Performance of skin ultrasound to measure skin involvement in different animal models of systemic sclerosis.
Animal models are widely used in systemic sclerosis (SSc) research. We set out to determine whether ultrasonography (US) could be used to assess skin fibrosis in two complementary SSc-models: the bleomycin-induced dermal fibrosis model and the tight-skin 1 mouse model. Back skin thickness was measured using a high-frequency ultrasound dedicated to the small animal. There was no significant difference in dermal thickness measured by US between mice injected with bleomycin and those treated with NaCl. These results were inconsistent with histological analyses. Mean US hypodermal thickness was significantly higher in tight-skin 1 mice as compared with Pa/Pa control subgroup (p = 0.02). Histologic and US measures of dermal and hypodermal thicknesses in this model were well correlated (r = 0.79). The intra-observer concordance was 0.96 for hypodermal thickness. US is reliable and sensitive in detecting hypodermal thickening in the tight-skin 1 mouse model. Further larger studies are warranted to better determine the place of US in SSc-research.


Bacterial fauna associating with chironomid larvae from lakes of Bengaluru city, India - A 16s rRNA gene based identification.
Chironomid larvae that inhabit in aquatic sediments play an important role as vector for bacterial pathogens. Its life cycle consists of four stages i.e. eggs, larvae, pupae and adult. In the present study we identified bacterial species associated with whole larvae of chironomids from 11 lake sediments of Bangalore region using 16s rRNA gene Sanger sequencing. We found that larvae from all lake sediments associated with bacterial species which include key pathogens. Totally we identified 65 bacterial isolates and obtained GenBank accession numbers (KX980423 - KX980487). Phylogenetic tree constructed using MEGA 7 software and tree analysis highlight the predominant bacterial community associated with larvae which include Enterobacteriaceae (43.08%; 28 isolates) and Aeromonas (24.62%; 16 isolates), Shewanella, Delftia, Bacillus (6.15%; 4 isolates each), Pseudomonas (4.62%; 3 isolates) and Exiguobacterium (3.08%; 2 isolates). Current findings state that among bacterial population Aeromonas, Enterobacter and Escherichia with serotypes are commonly associated with larvae in maximum lake points. In other hand Vibrio, Pseudomonas, Klebsiella, Shigella, Bacillus, and other bacterial species were identified moderately in all lakes. Interestingly, we identified first time Shigella Gram negative, rod shaped pathogenic organism of Enterobacteriaceae and Rheinheimera Gram negative, rod shaped organism associating chironomid larvae.


Shared decision making for patients with breast and gynecologic malignancies undergoing chemotherapy associated with persistent alopecia.
To assess patient-perceived involvement in shared decision making among those diagnosed with breast or gynecologic malignancies undergoing chemotherapy associated with persistent chemotherapy-induced alopecia (pCIA). We also sought to identify factors that influence shared decision making. We recruited patients from the Gynecologic Medical Oncology and Breast Medicine Services at a large academic center for this prospective cohort study. All patients were scheduled to start chemotherapy between June 1, 2017 and December 31, 2017. Following medical consultation, including discussion of the risk of pCIA, patients completed the 9-item Shared Decision Making Questionnaire (SDM-Q-9). Clinical and sociodemographic information was also collected. Univariate analysis was used to evaluate SDM-Q-9 total scores and their constituents for all variables. Sixty-one patients completed the survey. The median total SDM-Q-9 score was 95.6 (95% CI: 90-100). Most patients (n = 57, 93%) reported a high level of involvement (SDM-Q-9 total score > 66). There was no difference in total scores between patients with breast compared with gynecologic cancer (P > .05). By individual item, the scores for item Q1 ("My doctor made clear that a decision needs to be made") were significantly lower for Black patients and those with advanced disease (P < .05). Most patients indicated they were adequately involved in shared decision making regarding chemotherapy treatment options and their risk for pCIA. Patients from underrepresented populations and those with advanced disease may benefit from additional support from their clinicians to better address the anticipated psychosocial impacts of pCIA and facilitate the provision of optimal and equitable care.


Environmental reverberations of geopolitical risk and economic policy uncertainty resulting from the Russia-Ukraine conflict: A wavelet based approach for sectoral CO2 emissions.
After the COVID-19 pandemic, Russia invaded Ukraine in February 2022, and a natural gas crisis between the European Union (EU) and Russia has begun. These events have negatively affected humanity and resulted in economic and environmental consequences. Against this background, this study examines the impact of geopolitical risk (GPR) and economic policy uncertainty (EPU) caused by the Russia-Ukraine conflict, on sectoral carbon dioxide (CO2) emissions. To this end, the study analyzes data from January 1997 to October 2022 by using wavelet transform coherence (WTC) and time-varying wavelet causality test (TVWCT) approaches. The WTC results show that GPR and EPU reduce CO2 emissions in the residential, commercial, industrial, and electricity sectors, while GPR increases CO2 emissions in the transportation sector during the period from January 2019 to October 2022, which includes Russia-Ukraine conflict. The WTC analysis also indicates that the reduction in CO2 emissions provided by the EPU is higher than that of the GPR for several periods. According to the TVWCT, there are causal impacts of the GPR and the EPU on sectoral CO2 emissions, but the timing of the causal impacts differs between the raw and decomposed data. The results suggest that the EPU has a larger impact on reducing sectoral CO2 emissions during the Ukraine-Russia crisis and that production disruptions due to uncertainty have the greatest impact on reducing CO2 emissions in the electric power and transportation sectors.


Differential effects of ketoconazole on exposure to temsirolimus following intravenous infusion of temsirolimus.
Intravenous (i.v.) temsirolimus, a novel inhibitor of mammalian target of rapamycin, is approved for the treatment of advanced renal cell carcinoma and is being studied in patients with mantle cell lymphoma. Because temsirolimus and its primary metabolite, sirolimus, are metabolised by the cytochrome P450 3A4 pathway (CYP3A4), the potential exists for pharmacokinetic (PK) drug interactions with the numerous agents that modulate CYP3A4 isozyme activity. We investigated the effects of ketoconazole, a potent CYP3A4 inhibitor, on the PK profile of i.v. temsirolimus in healthy adults. Coadministration of 400 mg oral ketoconazole with 5 mg i.v. temsirolimus had no significant effect on temsirolimus maximum concentration (C(max)) or area under the concentration curve (AUC). However, mean AUC increased 3.1-fold and AUC(sum) (sum of temsirolimus plus sirolimus AUCs) increased 2.3-fold compared with temsirolimus alone. A single 5-mg dose of temsirolimus with ketoconazole was well tolerated, and there were no unexpected safety results. Therefore, in cancer patients receiving 25 mg i.v. temsirolimus, concomitant treatment with agents that have strong CYP3A4 inhibition potential should be avoided. If a concomitant strong CYP3A4 inhibitor is necessary, a temsirolimus dose reduction to 12.5 mg weekly should be considered.


Fluctuations in the polymerization of sickle hemoglobin. A simple analytic model.
Using the stochastic theory of chemical reactions and the theory of first passage times, a simple analytic expression is derived for the distribution of delay times that has been observed in studies of the polymerization kinetics of sickle hemoglobin under conditions where the polymerization progress curves exhibit stochastic variation. The rate of homogeneous nucleation can be readily extracted from such experiments using this expression. This work constitutes a significant addition to the rather limited number of examples where contact can be successfully made between the stochastic theory of chemical kinetics and experiment.


The relationship between infant lung function and the risk of wheeze in the preschool years.
There is evidence that perinatal lung development predicts childhood wheeze. However, very few studies have examined whether preschool wheeze is associated with lower premorbid lung function in early infancy, and as yet there is no information relating atopic and non-atopic preschool wheeze to early lung development. To examine the association between premorbid infant lung function and preschool wheeze, and to explore associations with atopic and non-atopic wheeze phenotypes. Infant lung function was measured in 147 healthy term infants aged 5-14 weeks. Rapid thoracoabdominal compression was performed during tidal breathing and at raised volume to measure maximal expiratory flow at functional residual capacity (V' max FRC) and forced expiratory volume in 0.4 sec (FEV(0.4)). Atopic status was determined by skin prick testing at 3 years and wheeze ascertained from parental questionnaires (1 and 3 years). Lower early infancy V' max FRC was associated with wheeze in both the first and third years of life (P=0.002 and 0.006, respectively). Lower early infancy FEV(0.4) was associated with wheeze in the first year (P=0.03). Compared to non-atopic children who did not wheeze, non-atopic children who wheezed in their third year of life had lower FEV(0.4) (P=0.02), while FEV(0.4) values of atopic children who wheezed were not significantly different (P=0.4). Lower premorbid infant lung function was present in infants who subsequently wheezed during the first and third years of life. Lower FEV(0.4) in early infancy was associated with non-atopic wheeze but not atopic wheeze at 3 years of age.


Stromal fibroblasts derived from mammary gland of bovine with mastitis display inflammation-specific changes.
Fibroblasts are predominant components of mammary stromal cells and play crucial roles in the development and involution of bovine mammary gland; however, whether these cells contribute to mastitis has not been demonstrated. Thus, we have undertaken biological and molecular characterization of inflammation-associated fibroblasts (INFs) extracted from bovine mammary glands with clinical mastitis and normal fibroblasts (NFs) from slaughtered dairy cows because of fractured legs during lactation. The functional contributions of INFs to normal epithelial cells were also investigated by using an in vitro co-culture model. We present evidence that the INFs were activated fibroblasts and showed inflammation-related features. Moreover, INFs significantly inhibited the proliferation and β-casein secretion of epithelial cells, as well as upregulated the expression of tumor necrosis factor-α and interleukin-8 in epithelial cells. These findings indicate that functional alterations can occur in stromal fibroblasts within the bovine mammary gland during mastitis, demonstrating the importance of stromal fibroblasts in bovine mastitis and its treatment.


[Study on Dormant Culture and Plant Regeneration via Cluster Buds of Gentiana straminea].
In order to provide scientific basis for micropropagation and cryopreservation of Gentiana straminea,plantlets were regenerated from dormant buds by cluster buds. Based on MS medium, dormant buds were inoculated in mediums containing different type and concentration of cytokinin and auxin for inducing cluster buds. 1/2MS medium with different concentration of auxin were used for inducing root. The medium of MS with 2.0 mg/L 6-BA, 0.01 mg/L NAA,30 g/L sucrose and 7 g/L agar was suitable for cluster buds' primary culture and subculture. The cluster buds inducing rate was 93. 3%. Multiple shoot clumps multiplication factor was 5.6. The medium of 1/2MS with 2.0 mg/L IAA, 0.5 mg/L IBA, 15 g/L sucrose and 7 g/L agar was suitable for root induction, its inducing rate was 93.5% with plantlets growing well. Plantlets regenerated from dormant buds of Gentiana straminea via cluster buds are established in this study.


Transcatheter aortic valve replacement through transcaval aortic access in a patient with duplicated inferior vena cava and poor iliofemoral anatomy.
Transthoracic (transapical and transaortic) access is inferior compared with femoral artery access. Percutaneous transcaval aortic access is a reasonable alternative approach that is being used in transcatheter aortic valve replacement (TAVR) in patients with poor iliofemoral anatomy. Duplicated Inferior vena cava (DIVC) is an uncommon abnormality. We report the case of 76-year-old lady with history of severe peripheral vascular disease, morbid obesity, diabetes, hypertension, hyperlipidemia and duplicated IVC that had severe symptomatic aortic stenosis. The patient had diffuse bilateral iliac disease precluding the arterial access required for TAVR. Other comorbidities made transthoracic access less desirable. We report the first successful Transcaval TAVR in a patient with DIVC.


Hypoxia and visualization of the stem cell niche.
It is widely accepted that mammalian stem cells reside in a specialized cellular and a cellular microenvironment called the niche. The niche contrary to other tissues is characterized by a low partial Oxygen pressure (ppO2). This microenvironment protects stem cells from deleterious effects of O2 on proteins and DNA, through the production of reactive oxygen species (ROS). In addition there is now solid evidence that this physiological hypoxia helps stem cells maintaining their major characteristics: multipotency and ability to differentiate and migrate from the niche to specialized tissues in order to fulfill the needs of the organism. Immuno Histological techniques can stain stem cells in situ by specific Abs (such as against CD34 and CD45 for Hematopoietic Stem Cells HSC). However, a universal marker of hypoxia is Hypoxia-Inducible Factor-1, HIF-1, which is stabilized by low ppO2 and acts as a transcription factor to regulate a vast array of genes downstream. HIF-1, together with pimonidazole, a chemical compound interacting with proteins that are reduced in a hypoxic environment, are bona fide markers of the stem cell niche.


Electrodeposited glucose oxidase/anionic clay for glucose biosensors design.
An amperometric glucose biosensor was developed using an anionic clay matrix (layered double hydroxide (LDH), Ni/Al-NO3) for the immobilization of glucose oxidase (GOx). The biofilm was prepared by electrodeposition of the clay and GOx and subsequent cross-linking with glutaraldeyde. The Pt surface modified with the Ni/Al-NO3 shows a much reduced noise, giving rise to a better signal to noise ratio for the currents relative to H2O2 oxidation, and a linear range for H2O2 determination wider than the one observed for bare Pt electrodes. Under the optimised operative conditions, the performances of the biosensor have been evaluated by measuring the steady-state currents (at +0.45 V versus SCE) to increasing concentrations of glucose in "air saturated" 0.1 M phosphate buffer (pH 7.0). Both batch and flow injection modes were explored. The response to glucose was linear up to 8.0 and 12.0 mM, and the sensitivities were 7.7+/-0.1 and 19.1+/-0.2 mA M(-1) cm(-2), respectively. The current response of the biosensors does not significantly change for 15 consecutive days in batch and for 10 days in flow, at least, if stored at 4 degrees C in phosphate buffer, when not in use. The effects of interferants and applicability to fruit juices and soft drinks analysis of the biosensor were also investigated.


Relationship between body weight and blood pressure and some metabolic parameters in psoriatic patients.
The relationship between body weight and blood pressure, total serum cholesterol, triglycerides, uric acid and glucose was investigated in 203 psoriatic patients in comparison with 904 healthy controls. In the psoriatic patients, these parameters were clearly related to their body weight. Those psoriatic patients of normal weight exhibited lower mean values of all the parameters compared with overweight psoriatic patients while they did not differ from control subjects of normal weight. Our results suggest that only overweight psoriatic patients exhibit the metabolic abnormalities frequently reported in the literature, while psoriatic patients of normal weight do not differ from the general population in this respect.


Laparoscopic versus open surgery for perihilar cholangiocarcinoma: a multicenter propensity score analysis of short- term outcomes.
Laparoscopic surgery (LS) has been increasingly applied in perihilar cholangiocarcinoma (pCCA). In this study, we intend to compare the short-term outcomes of LS versus open operation (OP) for pCCA in a multicentric practice in China. This real-world analysis included 645 pCCA patients receiving LS and OP at 11 participating centers in China between January 2013 and January 2019. A comparative analysis was performed before and after propensity score matching (PSM) in LS and OP groups, and within Bismuth subgroups. Univariate and multivariate models were performed to identify significant prognostic factors of adverse surgical outcomes and postoperative length of stay (LOS). Among 645 pCCAs, 256 received LS and 389 received OP. Reduced hepaticojejunostomy (30.89% vs 51.40%, P = 0.006), biliary plasty requirement (19.51% vs 40.16%, P = 0.001), shorter LOS (mean 14.32 vs 17.95 d, P < 0.001), and lower severe complication (CD ≥ III) (12.11% vs. 22.88%, P = 0.006) were observed in the LS group compared with the OP group. Major postoperative complications such as hemorrhage, biliary fistula, abdominal abscess, and hepatic insufficiency were similar between LS and OP (P > 0.05 for all). After PSM, the short-term outcomes of two surgical methods were similar, except for shorter LOS in LS compared with OP (mean 15.19 vs 18.48 d, P = 0.0007). A series subgroup analysis demonstrated that LS was safe and had advantages in shorting LOS. Although the complex surgical procedures, LS generally seems to be safe and feasible for experienced surgeons. NCT05402618 (date of first registration: 02/06/2022).


Purines and prostaglandins as regulators in the coronary circulation.
In the isolated rat heart perfused at constant flow a bolus injection of an adenine nucleotide reduced coronary perfusion pressure and was negatively inotropic (ATP greater than ADP greater than AMP). Adenosine had no effect on perfusion pressure or contractile force. ATP and ADP stimulated production of PGI2 from the coronary bed. Perfusion with indomethacin completely inhibited PGI2 production but had no effect on the reduction in perfusion pressure and cardiac function produced by ATP. Purinoceptors in the perfused rat heart are of the P2 type and responses produced by purinoceptor activation are not mediated by PGI2.


Respiratory disturbance during recovery from etomidate anaesthesia.
A case is described in which recovery from the administration of a single dose of etomidate was complicated by periodic episodes of unconsciousness, tremor and apnoea. Subsequent investigations did not reveal any evidence of neurological disease.


A single-center experience with eccentric syringomyelia found with pediatric Chiari I malformation.
Eccentric syringes associated with Chiari I malformation have received scant attention in the medical literature. Herein, we describe our experience and long-term outcome in patients with this finding. A retrospective analysis of a Chiari I database was performed. Patients known to have an associated syringomyelia were then further analyzed for the type of syrinx present. When an eccentric syrinx was noted, the symptoms and postoperative course of these patients were analyzed. Of well over 500 operative cases of Chiari I malformation, roughly 70 % (pre-syrinx and minimally dilated central canals were excluded) were found to have an associated syringomyelia. Of these, four patients were found to have an eccentrically positioned syrinx. Three of these cases presented with symptoms referable to the side of the eccentric syrinx. Postoperatively, cases with both a central and eccentrically located syrinx were found to have a greater decrease in the size of the central portion of their syrinx compared to the eccentrically located portion. Symptoms decreased in all patients. The minority of our patients with hindbrain-induced syringomyelia were found to have an eccentrically located syrinx. Of these, most will have symptoms localized to the abnormal fluid-filled cavity, and these may not decrease in size as much as centrally located syringes following posterior fossa decompression. However, all symptoms decreased in those operated. Based on the literature, non-hindbrain-induced syringomyelia is more likely to result in an eccentrically placed syrinx. The mechanism for this is yet to be elucidated.


Blue babies: when to intervene.
Cyanotic congenital heart disease is an important cause of morbidity and mortality in neonates, infants and children. Presently facilities for treatment for most of these cases are available in many centres in India also. The most important factor is awareness, complete correct diagnosis and timely intervention either palliative or corrective. In admixture lesions very early intervention is needed so as to avoid development of pulmonary vascular obstructive disease which develops early in these cases. Some of the patients of reduced pulmonary blood flow may need aggressive intervention in neonatal period. The patient of tetralogy of Fallot should have surgical correction before their first birthday. Due to great variation in the anatomical substrate and natural history each case needs complete meticulous evaluation. Later a plan of management keeping in view the natural history of the uncorrected lesion should be made.


Approaching a consensus: psychosocial support services for solid organ transplantation programs.
Solid organ transplantation has become an accepted treatment for individuals with end-stage organ dysfunction. Criteria are being developed in the United States to determine medical eligibility for transplant candidates and competencies for transplant centers and physicians. To date, similar criteria for psychosocial services have not been developed. We queried participants in a specialty psychosocial transplant meeting to determine their views of which psychosocial services are essential to the comprehensive care of transplant patients in the United States. There was broad based multidisciplinary support for proactive pretransplant screening to discern individual psychosocial needs; focused pretransplant interventions to improve candidacy and future compliance; and posttransplant programs that address psychosocial, rehabilitation, and financial issues. Among psychosocial providers of solid organ transplantation services, there is support for expanding routine screening and support services to individuals who are candidates for and undergo solid organ transplantation.


Acetylcholine receptor/channel molecules of insects.
Acetylcholine-gated ion channels of the nicotinic type are abundant in the nervous system of insects. The channels are permeable to Na+, K+ and probably Ca(2+), and unlike most vertebrate neuronal nicotinic acetylcholine receptors the receptor/channel molecule is blocked by alpha-bungarotoxin (alpha-Bgt). Such alpha-Bgt-sensitive receptors are present at synapses and on cell bodies of insect neurones. Single channel recordings have shown the existence of multiple conductances of nAChRs. Studies on several different insect preparations have provided evidence for more than one open state and several closed states of insect nAChRs. Functional insect nAChR channels have now been investigated in situ, following reconstitution of a purified protein in bilayers, and as a result of expressing in Xenopus oocytes messenger RNA encoding receptor subunits.


Protective efficacy of an inactivated vaccine against H9N2 avian influenza virus in ducks.
Wild ducks play an important role in the evolution of avian influenza viruses (AIVs). Domestic ducks in China are known to carry and spread H9N2 AIVs that are thought to have contributed internal genes for the recent outbreak of zoonotic H7N9 virus. In order to protect animal and public health, an effective vaccine is urgently needed to block and prevent the spread of H9N2 virus in ducks. We developed an inactivated H9N2 vaccine (with adjuvant Montanide ISA 70VG) based on an endemic H9N2 AIV and evaluated this vaccine in ducks. The results showed that the inactivated H9N2 vaccine was able to induce a strong and fast humoral immune response in vaccinated ducks. The hemagglutination inhibition titer in the sera increased fast, and reached its peak of 12.3 log2 at 5 weeks post-vaccination in immunized birds and remained at a high level for at least 37 weeks post-vaccination. Moreover, viral shedding was completely blocked in vaccinated ducks after challenge with a homologous H9N2 AIV at both 3 and 37 weeks post-vaccination. The results of this study indicate that the inactivated H9N2 vaccine induces high and prolonged immune response in vaccinated ducks and are efficacious in protecting ducks from H9N2 infection.


Multilayered non-uniform atomic force microscope piezoelectric microcantilever control and vibration analysis considering different excitation based on the modified couple stress theory.
Atomic force microscope (AFM) is one of the most powerful tools for surface scanning, force measurement, and nano-manipulation. To improve its performance, vibration and control of AFM micro-cantilever (MC) should be studied. Hysteresis, as an undesired phenomenon affecting vibration amplitude and phase, is also another important issue to be examined. In this paper, vibration analysis and control of a ZnO non-uniform multi-layered piezoelectric MC has been investigated in non-contact mode. A modified couple stress theory has been used to obtain the strain energy for modeling the MC. In order to control the amplitude, a sliding mode controller (SMC) has been utilized on AFM, due to its application in uncertain and nonlinear systems. For applying the control signal, two methods of piezo and base actuation are studied. The results are compared with proportional integral derivative (PID) control method and it is demonstrated that SMC method reduces the control input close to the surface and increases the accuracy near the surface. In addition to MC control, hysteresis amplitude and phase differences are investigated by applying the Prandtl-Ishlinskii model. Also, surface topography is studied with hysteresis. The simulations show backward phase difference and an increase in amplitude, accordingly.


Citrinin mycotoxin recognition and removal by naked magnetic nanoparticles.
Citrinin is a nephrotoxic mycotoxin which can be synthesized by Monascus mold during the fermentation process in foods. Monascus, generally described as red mold, is a red-pigmented filamentous fungus attracting a great interest for the production of natural dyes and cholesterol-lowering statins. We individuated a specie of Monascus producing high amount of natural dyes. However, this high pigmentation was correlated with the production of citrinin. Peculiar magnetic nanoparticles, synthesized in-house and called "Surface Active Maghemite Nanoparticles" (SAMNs), are proposed as an efficient and reliable mean for citrinin removal from Monascus treated foods. The nanomaterial efficiency for citrinin binding was proved on Monascus suspensions, and SAMN@citrinin complex was characterized by Mӧssbauer spectroscopy and magnetization measurements, showing that SAMNs resulted structurally and magnetically well conserved after citrinin binding. SAMNs are excellent and stable magnetic nano-carrier for toxin removal, which can be applied in food industry.


Serially Combining Epidemiological Designs Does Not Improve Overall Signal Detection in Vaccine Safety Surveillance.
Vaccine safety surveillance commonly includes a serial testing approach with a sensitive method for 'signal generation' and specific method for 'signal validation.' The extent to which serial testing in real-world studies improves or hinders overall performance in terms of sensitivity and specificity remains unknown. We assessed the overall performance of serial testing using three administrative claims and one electronic health record database. We compared type I and II errors before and after empirical calibration for historical comparator, self-controlled case series (SCCS), and the serial combination of those designs against six vaccine exposure groups with 93 negative control and 279 imputed positive control outcomes. The historical comparator design mostly had fewer type II errors than SCCS. SCCS had fewer type I errors than the historical comparator. Before empirical calibration, the serial combination increased specificity and decreased sensitivity. Type II errors mostly exceeded 50%. After empirical calibration, type I errors returned to nominal; sensitivity was lowest when the methods were combined. While serial combination produced fewer false-positive signals compared with the most specific method, it generated more false-negative signals compared with the most sensitive method. Using a historical comparator design followed by an SCCS analysis yielded decreased sensitivity in evaluating safety signals relative to a one-stage SCCS approach. While the current use of serial testing in vaccine surveillance may provide a practical paradigm for signal identification and triage, single epidemiological designs should be explored as valuable approaches to detecting signals.