Differential expression and functional diversification of diverse immunoglobulin domain-containing protein (DICP) family in three gynogenetic clones of gibel carp.
Diverse immunoglobulin (Ig) domain-containing protein (DICP) family is a novel bony fish-specific multi-gene family encoding diversified immune receptors. However, their function and the implication of binding partners remain unknown. In this study, we first identified 28 DICPs from three gibel carp gynogenetic clones and revealed their high variability and clone-specific feature. After crucian carp herpesvirus (CaHV) infection, these DICPs were significantly upregulated in head kidney, kidney and spleen. The up-regulation folds in clone A+, F and H were related to the susceptibility to CaHV, progressively increasing from resistant clone to susceptible clone. Overexpression of gibel carp DICPs inhibited interferon (IFN) and viperin promoter-driven luciferase activity. The additions of E. coli extracts and lipid A significantly enhanced the inhibition effect. In addition, gibel carp DICPs can interact with SHP-1 and SHP-2. These findings suggest that gible carp DICPs, as inhibitory receptors, might specifically recognize lipid A, and then interact with SHP-1 and SHP-2 to inhibit the induction of IFN and ISGs.


[Expression and assessment of double genes of tyrosine hydroxylase gene and aromatic L-amino acid decarboxylase gene in vitro].
The characteristic pathological changes of Parkinson s disease (PD) include a severe loss of dopamine neurons in the substantia nigra and a severe decrease in dopamine in the striatum. Since the expression of tyrosine hydroxylase (TH) and aromatic L-amino acid decarboxylase (AADC) in the biosynthetic pathway for dopamine are low, a promising approach to the gene therapy of PD is to augment the gene expression of the enzymes in the biosynthetic pathway for dopamine. In the present study, human TH and AADC genes were reconstructed into retrovirous vectors pLHCX and pLNCX(2) respectively. Then pLHCX/TH and pLNCX(2)/AADC were transfected into packaging cell line PA317 with liposome. PA317/TH and PA317/AADC were selected by different antibiotics. Gene expression was examined by methods of immunohistochemistry and in situ hybridization. The catalytic activity of two cloned gene enzymes was assessed in vitro by HPLC-EC. Immunocytochemical staining showed that TH and AADC were expressed efficiently in vitro. Both TH and AADC mRNA were transcripted in PA317 cell lines by using in situ hybridazation. HPLC-EC experiments revealed that the transfected cells produced a significantly higher level of dopamine and L-dopa than the untransfected cells. The two genetically modified cells could improve the production of L-dopa and dopamine in response to suitable substrate. The present results suggest that not only recombinant TH and AADC genes are successfully expressed in vitro, but also the enzymes have respective functional activities. These results have set up a way for in vivo gene therapy of PD with TH and AADC genes.


Polarization-dependence of the Raman response of free-standing strained Ce0.8Gd0.2O2 membranes.
Square-shaped Ce0.8Gd0.2O2 (GDC) membranes are prepared by microstructuring techniques from (111)-oriented, polycrystalline GDC thin films. The strain state of the membranes is investigated by micro-Raman mapping using polarized excitation light. Using circularly polarized excitation, the maps of the Raman shifts reveal circular contour lines in concordance with the quadratic shape of the membrane and with optical investigations of the residual strain distribution. In contrast, asymmetric contours of the maps of the Raman shifts exhibiting a two-fold symmetry are found when using linearly polarized excitation. The contour plots for a linear polarization perpendicular or parallel to the local curvature are rotated by 90°. This behavior is caused by the polarization dependence of three overlapping Raman modes arising from the splitting of the triply degenerate F2g mode due to strain. The contribution of their Raman intensity to the overall Raman signal depends on the measurement geometry and the polarization of the incoming and scattered light. Varying the polarization of the incoming excitation light results in different averaging of the Raman-active modes contributing to the broad Raman signal observed. These results clearly demonstrate that polarization-dependent Raman measurements have the potential to yield additional insight into the local strain distribution in free-standing oxide membranes.


[New insight in pathogenesis of podocyte disfunction in minimal change disease].
Minimal change disease (MCD) is a common pathological type of nephrotic syndrome. Its main histology is the fusion of podocyte foot process. The pathogenesis of MCD is not clear, but previously it was thought to be related to immune mechanism. In recent years more studies show that podocyte injury is the key link in the pathogenesis of MCD. In MCD mouse model and human kidney tissues, the expressions of podocyte slit membrane protein-nephrin and podocin, skeleton protein-synaptopodin are decreased, and the expression of synaptopodin is correlated with the response to hormone therapy. In addition, newest studies focused on another two potocyte associated proteins, CD80 and Angiopoietin-like-4. CD80, a T cell stimulating molecule, is expressed in potocyte. Kappa B gene sequences can be activated by external microbes, antigens through acting potocytes, which can induce the upregulation of CD80 expression, cytoskeletal protein damage and the glomerular filtration rate changes, resulting in proteinuria. Angiopoietin-like-4 can be expressed in normal potocytes, but over-expression of angiopoietin-like-4 may injure the GBM charge barrier and induce the foot process fusion, leading to MCD. However, further studies on the factors inducing CD80 and Angiopoietin-like-4 expression, and the interaction between glomerular basement membrane and the two proteins are needed. Based on the mechanism of MCD, NF-kappa B inhibitors and sialylation therapy would be a novel non-immune therapy for MCD.


Changes in corneal curvature and visual acuity in North Indian adults after pterygium excision with modified sutureless, glueless limbal-conjunctival autograft.
To identify the exact time point during after following pterygium excision with a modified technique of sutureless, glueless limbal-conjunctival autograft, when stabilization of the change in corneal curvature is achieved; correlate size of pterygium with uncorrected visual acuity and astigmatism at baseline, and assess changes in these parameters postoperatively over time. This prospective study longitudinally assessed 30 eyes of 30 north Indian adults with primary pterygium encroaching upon ≥1 mm of the cornea pre- and postoperatively at 1 week and then monthly for 4 months, recording uncorrected (UCVA) and best-corrected logMAR visual acuity, astigmatism and keratometry. Results were analyzed using ANOVA, Mauchly's test of sphericity with Greenhouse-Geisser correction, and post-hoc test using Bonferroni correction. Pearson's correlation coefficient r > 0.5 was considered clinically significant, and P < 0.05 statistically significant. Pterygium size was well correlated with pre-operative astigmatism (r = 0.867, P < 0.001) and pre-operative UCVA (r = 0.856, P < 0.001). There was mean improvement of 0.43 logMAR units of visual acuity (P < 0.00001), a mean increase of 0.79D of keratometric value for the flatter meridian (P < 0.00001) and a mean reduction of 2.00D of astigmatism (P < 0.00001). At 2-month follow-up, the keratometric value for the flatter meridian approached the final keratometric reading at 4 months such that the difference was not significant (t = 1.185, P = 0.245). There were no significant complications or recurrence during the follow-up period. Pterygium excision with modified autograft reduced corneal astigmatism and improved visual acuity comparable to classical technique. Alteration in corneal curvature stabilizes 2 months after surgery, when spectacle correction can be given to patients.


Video-assisted thoracic surgery mediastinal germ cell metastasis resection.
Thoracoscopy can be safely used for dissection of masses in the visceral mediastinum. We report the case of a 31-year-old man affected by metastatic germ cell tumour and successfully treated with a 3-port posterior approach video-assisted thoracic surgery.


Space Structure and Clustering of Categorical Data.
Learning from categorical data plays a fundamental role in such areas as pattern recognition, machine learning, data mining, and knowledge discovery. To effectively discover the group structure inherent in a set of categorical objects, many categorical clustering algorithms have been developed in the literature, among which k -modes-type algorithms are very representative because of their good performance. Nevertheless, there is still much room for improving their clustering performance in comparison with the clustering algorithms for the numeric data. This may arise from the fact that the categorical data lack a clear space structure as that of the numeric data. To address this issue, we propose, in this paper, a novel data-representation scheme for the categorical data, which maps a set of categorical objects into a Euclidean space. Based on the data-representation scheme, a general framework for space structure based categorical clustering algorithms (SBC) is designed. This framework together with the applications of two kinds of dissimilarities leads two versions of the SBC-type algorithms. To verify the performance of the SBC-type algorithms, we employ as references four representative algorithms of the k -modes-type algorithms. Experiments show that the proposed SBC-type algorithms significantly outperform the k -modes-type algorithms.


Huntington's disease accelerates epigenetic aging of human brain and disrupts DNA methylation levels.
Age of Huntington's disease (HD) motoric onset is strongly related to the number of CAG trinucleotide repeats in the huntingtin gene, suggesting that biological tissue age plays an important role in disease etiology. Recently, a DNA methylation based biomarker of tissue age has been advanced as an epigenetic aging clock. We sought to inquire if HD is associated with an accelerated epigenetic age. DNA methylation data was generated for 475 brain samples from various brain regions of 26 HD cases and 39 controls. Overall, brain regions from HD cases exhibit a significant epigenetic age acceleration effect (p=0.0012). A multivariate model analysis suggests that HD status increases biological age by 3.2 years. Accelerated epigenetic age can be observed in specific brain regions (frontal lobe, parietal lobe, and cingulate gyrus). After excluding controls, we observe a negative correlation (r=-0.41, p=5.5×10-8) between HD gene CAG repeat length and the epigenetic age of HD brain samples. Using correlation network analysis, we identify 11 co-methylation modules with a significant association with HD status across 3 broad cortical regions. In conclusion, HD is associated with an accelerated epigenetic age of specific brain regions and more broadly with substantial changes in brain methylation levels.


Detection of anti-interferon-gamma autoantibodies in subjects infected by Mycobacterium tuberculosis.
Among the cytokines involved in defensive mechanisms against Mycobacterium tuberculosis infection, special attention has been given to interferon-gamma (IFN-gamma); a local synthesis of this cytokine as well as IL-2 (type 1 cytokines) at the site of disease in patients with tuberculous pleuritis has been demonstrated. Moreover, high levels of IgG autoantibodies against IFN-gamma have been shown in several clinical situations. It has been suggested that these antibodies could serve to limit the intensity or duration of the immune response or be able to interfere with the pathophysiological effects of IFN-gamma. To investigate the potential role of anti-IFN-gamma antibodies in the course of M. tuberculosis infection. Investigation of the presence of these antibodies in sera from healthy and ill subjects infected with M. tuberculosis in relation to the extent of the disease and the presence of IFN-gamma in sera by enzyme-linked-immunosorbent assay (ELISA). In order to investigate the presence of these antibodies at the site of infection we included 12 pleural fluids from tuberculosis patients and 9 pleural fluids from other origins. In the course of M. tuberculosis infection the production of anti-IFN-gamma IgG antibodies is induced, being particularly higher in healthy skin test converters. Among tuberculosis patients, the presence of anti-IFN-gamma autoantibodies is significantly associated with detectable levels of the cytokine in sera. Levels of anti-IFN-gamma antibodies in moderately advanced and far advanced tuberculosis patients are significantly greater than in healthy individuals. These antibodies increase at the site of infection. Anti-IFN-gamma antibodies must be considered as a new element in the immune response to M. tuberculosis. It would be of great interest to investigate this point especially at the site of infection.


Effects of beta-adrenergic blockade on vasodepressor reaction in patients with vasodepressor syncope.
The mechanism of vasodepressor reaction induced by head-up tilt test in patients with vasodepressor syncope is not clearly understood. We hypothesized that an abnormal alteration of beta-adrenergic transmission could be involved in these patients. We measured plasma catecholamine concentration during tilt and density of beta-adrenoceptors and tested the effects of beta-adrenergic blockers in the prevention of the vasodepressor reaction in patients with vasodepressor syncope. Ten patients had reproducibly induced vasodepressor syncope (mean 3.1 +/- 0.3 episodes in each patient) with head-up tilt (80 degrees) for 10 minutes with isoproterenol infusion (1 to 3 micrograms/min). Syncope occurred at 6.3 +/- 1.7 minutes during tilt with isoproterenol infusion. The plasma norepinephrine concentration before administration of beta-blocker was significantly elevated during tilt compared to the supine position (0.347 +/- 0.079 ng/ml in supine position with isoproterenol vs 0.468 +/- 0.082 ng/ml at 3 minutes of tilt, p < 0.001, and vs 0.503 +/- 0.106 ng/ml at the onset of vasodepressor reaction, p < 0.005; n = 8). Plasma norepinephrine after administration of the selective beta 1-adrenergic blocker metoprolol (40 mg/day) was similarly elevated (0.282 +/- 0.071 ng/ml in supine position with isoproterenol vs 0.390 +/- 0.078 ng/ml at 3 minutes of tilt, p < 0.05, n = 6; and vs 0.547 +/- 0.152 ng/ml at the onset of vasodepressor reaction, p < 0.001, n = 3).(ABSTRACT TRUNCATED AT 250 WORDS)


Evaluating Device Design and Cleanability of Orthopedic Device Models Contaminated with a Clinically Relevant Bone Test Soil.
Reusable medical devices need to be cleaned prior to disinfection or sterilization and subsequent use to prevent infections. The cleanability of medical devices depends in part on the design of the device. This study examined how models of orthopedic medical devices of increasing complexity retain calcium phosphate bone cement, a relevant test soil for these devices. The dye Alizarin Red S and micro-computed tomography (μCT) were used to assess the amount and location of bone cement debris in a series of model orthopedic devices. Testing was performed after soiling and cleaning once, and soiling and cleaning 10 times. The color change of the dye after reacting with the bone cement was useful for indicating the presence of bone cement in these models. High-resolution μCT analysis provided the volume and location of the bone cement. Models that were more complex retained significantly more bone debris than simpler designs. Model devices repeatedly soiled and cleaned 10 times retained significantly more bone debris than those soiled and cleaned once. Significantly more bone cement was retained in the more complex lumen structures. This information may be useful in designing reusable orthopedic devices, and other complex medical devices with lumens.


[Neurologic emergencies in children].
Neuropediatric emergencies are reviewed. In particular in this topic the Authors point out the diseases in which an immediate treatment is required. Hypoxic ischemic encephalopathy, acute neonatal metabolic disease, seizures disorders and status epilepticus, meningitis, encephalitis, post viral neurological syndromes, acute hemiplegia, coma, acute endocranial hypertension are discussed with special emphasis on the possible causes and treatment.


Haplotype distribution and association of candidate genes with salt tolerance in Indian wild rice germplasm.
The association of natural genetic variations of salt-responsive candidate genes belonging to different gene families with salt-tolerance phenotype and their haplotype variation in different geographic regions. Soil salinity covers a large part of the arable land of the world and is a major factor for yield losses in salt-sensitive crops, such as rice. Different gene families that respond to salinity have been identified in rice, but limited success has been achieved in developing salt-tolerant cultivars. Therefore, 21 salt stress-responsive candidate genes belonging to different gene families were re-sequenced to analyse their genetic variation and association with salt tolerance. The average single nucleotide polymorphism (SNP) density was 16 SNPs per kbp amongst these genes. The identified nucleotide and haplotype diversity showed comparatively higher genetic variation in the transporter family genes. Linkage disequilibrium (LD) analysis showed significant associations of SNPs in BADH2, HsfC1B, MIPS1, MIPS2, MYB2, NHX1, NHX2, NHX3, P5CS1, P5CS2, PIP1, SIK1, SOS1, and SOS2 genes with the salt-tolerant phenotype. A combined analysis of SNPs in the 21 candidate genes and eight other HKT transporter genes produced two separate clusters of tolerant genotypes, carrying unique SNPs in the ion transporter and osmoticum-related genes. Haplotype network analysis showed all the major and few minor alleles distributed over distant geographic regions. Minor haplotypes may be recently evolved alleles which migrated to distant geographic regions and may represent recent expansion of Indian wild rice. The analysis of genetic variation in different gene families identified the relationship between adaptive variations and functional significance of the genes. Introgression of the identified alleles from wild relatives may enhance the salt tolerance and consequently rice production in the salinity-affected areas.


Which type of fear of cancer progression contributes to the quality of life of Romanian cancer patients during the COVID-19 pandemic?
Fear of cancer progression (FoP) is one of the most frequently reported unmet needs invoked by the majority of cancer patients, which may significantly impair the quality of life (QoL) of patients. The major objective of the present cross-sectional study was to investigate the specificities of the relationship between different dimensions and intensity of FoP and different aspects of patients' QoL during the COVID-19 pandemic in Romania. A nationwide sample of 330 participants completed a survey, including measures of demographic characteristics, medical variables, QoL, and FoP. Multivariate General Linear and Hierarchical Regression Models were conducted in order to assess the relationship between variables. Our results indicate that less than a quarter of the sample experienced low, between 63 and 70% moderate, and 15% high levels of FoP. Our results also indicate that anxiety/worry related to the possibility of progression of the disease, and loss of independence produced significant differences with large effect sizes in all the dimensions of QoL. Our results indicate that besides affective reactions, the fear of cancer survivors to lose independence, not being able to attend to their own lives, seems to be a considerable threat, especially in the context of Romanian health system which has difficulties in offering qualitative psychosocial care for cancer patients. The idea that patients will have to rely on others and may not function well independently, not being able to attend to their own lives, seems to be a considerable threat, next to the experienced affective reactions per se.


Ab initio lifetime correction to scattering states for time-dependent electronic-structure calculations with incomplete basis sets.
We propose a method for obtaining effective lifetimes of scattering electronic states for avoiding the artificial confinement of the wave function due to the use of incomplete basis sets in time-dependent electronic-structure calculations of atoms and molecules. In this method, using a fitting procedure, the lifetimes are extracted from the spatial asymptotic decay of the approximate scattering wave functions obtained with a given basis set. The method is based on a rigorous analysis of the complex-energy solutions of the Schrödinger equation. It gives lifetimes adapted to any given basis set without using any empirical parameters. The method can be considered as an ab initio version of the heuristic lifetime model of Klinkusch et al. [J. Chem. Phys. 131, 114304 (2009)]. The method is validated on H and He atoms using Gaussian-type basis sets for the calculation of high-harmonic-generation spectra.


Disrupted apical exocytosis of cargo vesicles causes enteropathy in FHL5 patients with Munc18-2 mutations.
Familial hemophagocytic lymphohistiocytosis 5 (FHL5) is an autosomal recessive disease caused by mutations in STXBP2, coding for Munc18-2, which is required for SNARE-mediated membrane fusion. FHL5 causes hematologic and gastrointestinal symptoms characterized by chronic enteropathy that is reminiscent of microvillus inclusion disease (MVID). However, the molecular pathophysiology of FHL5-associated diarrhea is poorly understood. Five FHL5 patients, including four previously unreported patients, were studied. Morphology of duodenal sections was analyzed by electron and fluorescence microscopy. Small intestinal enterocytes and organoid-derived monolayers displayed the subcellular characteristics of MVID. For the analyses of Munc18-2-dependent SNARE-protein interactions, a Munc18-2 CaCo2-KO model cell line was generated by applying CRISPR/Cas9 technology. Munc18-2 is required for Slp4a/Stx3 interaction in fusion of cargo vesicles with the apical plasma membrane. Cargo trafficking was investigated in patient biopsies, patient-derived organoids, and the genome-edited model cell line. Loss of Munc18-2 selectively disrupts trafficking of certain apical brush-border proteins (NHE3 and GLUT5), while transport of DPPIV remained unaffected. Here, we describe the molecular mechanism how the loss of function of Munc18-2 leads to cargo-selective mislocalization of brush-border components and a subapical accumulation of cargo vesicles, as it is known from the loss of polarity phenotype in MVID.


A Novel Approach to Predict Core Residues on Cancer-Related DNA-Binding Domains.
Protein-DNA interactions are involved in different cancer pathways. In particular, the DNA-binding domains of proteins can determine where and how gene regulatory regions are bound in different cell lines at different stages. Therefore, it is essential to develop a method to predict and locate the core residues on cancer-related DNA-binding domains. In this study, we propose a computational method to predict and locate core residues on DNA-binding domains. In particular, we have selected the cancer-related DNA-binding domains for in-depth studies, namely, winged Helix Turn Helix family, homeodomain family, and basic Helix-Loop-Helix family. The results demonstrate that the proposed method can predict the core residues involved in protein-DNA interactions, as verified by the existing structural data. Given its good performance, various aspects of the method are discussed and explored: for instance, different uses of prediction algorithm, different protein domains, and hotspot threshold setting.


Relationship Between Self-Perceived Health, Vitality, and Posttraumatic Growth in Liver Transplant Recipients.
Our objective was to analyze the differences in posttraumatic growth in 240 liver transplant recipients based on two factors. First, self-perceived health: better (Group 1 = G1) and worse (Group 2 = G2). Second, vitality: more (Group 3 = G3) and less (Group 4 = G4). The Posttraumatic Growth Inventory, SF-36 Health Survey (Item 2) and SF-12 Health Survey (vitality dimension) were used. Firstly, analyzing main effects recipients with better (G1) compared to worse (G2) self-perceived health, showed greater posttraumatic growth. Interaction effects were found on essential posttraumatic growth domains such as new possibilities (p = 0.040), personal strength (p = 0.027), and appreciation of life (p = 0.014). Statistically significant differences showed that among transplant recipients with worse self-perceived health (G2), those with more vitality had higher levels on abovementioned posttraumatic growth dimensions. However, in transplant recipients with better self-perceived health (G1) respective dimensions were not significantly influenced by the level of vitality. Among the recipients with less vitality (G4), those with better self-perceived health showed higher scores on abovementioned posttraumatic growth dimensions. We conclude that positive self-perceived health might compensate for a lack of vitality as well as a high level of vitality may compensate for negative self-perceived health regarding the development of crucial aspects of posttraumatic growth after liver transplantation.


Can stimulant rebound mimic pediatric bipolar disorder?
The authors describe the case of a 7-year-old girl diagnosed with attention deficit hyperactivity disorder (ADHD) who, following an unsuccessful trial of stimulant medication and subsequent mood symptoms, was diagnosed with bipolar disorder. Following a comprehensive, multidisciplinary assessment, and withdrawal of her complex medication regimen, she was rediagnosed with ADHD. She displayed a positive response to behavioral parent training and pharmacological treatment with a long-acting stimulant. The case illustrates the benefits of a comprehensive, multidisciplinary evaluation and multimodal treatment. Her dramatic response to the long-acting stimulant suggests that many of her affective symptoms were due to stimulant "rebound" versus bipolar disorder. This case highlights the complexities of differentiating severe ADHD from bipolar disorder and suggests that stimulant rebound and other iatrogenic effects should be considered during the differential diagnostic process as potential mimics of bipolar disorder.


Stroke Characteristics in a Cohort of Hmong American Patients.
Background Prior studies have indicated high rates of vascular risk factors, but little is known about stroke in Hmong. Methods and Results The institutional Get With The Guidelines (GWTG) database was used to identify patients discharged with acute ischemic stroke, intracerebral hemorrhage, or subarachnoid hemorrhage between 2010 and 2019. Hmong patients were identified using clan names and primary language. Univariate analysis was used to compare Hmong and White patients. A subarachnoid hemorrhage comparison was not conducted because of the small sample size. We identified 128 Hmong patients and 3084 White patients. Hmong patients had more prevalent hemorrhagic stroke (31% versus 15%; P<0.0016). In the acute ischemic stroke cohort, compared with White patients, Hmong patients were younger (60±13 versus 71±15 years; P<0.0001), presented to the emergency department almost 4 hours later; and had a lower thrombolysis usage rate (6% versus 14%; P=0.03496), worse lipid profile, higher hemoglobin A1C, similar stroke severity, and less frequent discharge to rehabilitation facilities. The most common ischemic stroke mechanism for Hmong patients was small-vessel disease. In the intracerebral hemorrhage cohort, Hmong patients were younger (55±13 versus 70±15 years; P<0.0001), had higher blood pressure, and had a lower rate of independent ambulation on discharge (9% versus 30%; P=0.0041). Conclusions Hmong patients with stroke were younger and had poorer risk factor control compared with White patients. There was a significant delay in emergency department arrival and low use of acute therapies among the Hmong acute ischemic stroke cohort. Larger studies are needed to confirm these observations, but action is urgently needed to close gaps in primary care and stroke health literacy.


Vaginal Vault Suspension at Hysterectomy for Prolapse - Myths and Facts, Anatomical Requirements, Fixation Techniques, Documentation and Cost Accounting.
Vaginal vault suspension during hysterectomy for prolapse is both a therapy for apical insufficiency and helps prevent recurrence. Numerous techniques exist, with different anatomical results and differing complications. The description of the different approaches together with a description of the vaginal vault suspension technique used at the Department for Urogynaecology at St. Hedwig Hospital could serve as a basis for reassessment and for recommendations by scientific associations regarding general standards.


Prophylactic antibiotics after severe trauma: more is not better.
After severe trauma, physicians frequently use multiple antibiotics for prolonged periods of time to prevent sepsis, based on intuition rather than scientific evidence. Over a 1-year period (January-December 1999) we included prospectively 112 critically injured patients who required an operation and/or chest tube insertion and stayed for more than 2 days in the intensive care unit (ICU). Of these patients, 46 received a single prophylactic antibiotic for 24 hours (group SING+SHORT), and 66 received one or more prophylactic antibiotics for more than 24 hours (group MULT+LONG), based on physician discretion. Twenty-seven outcome parameters were collected to compare the effect of the different prophylactic antibiotic regimens. The two groups were similar in regard to overall injury severity, age, gender, mechanism of injury, and physiologic condition on admission. However, more SING+SHORT patients had an abdominal operation (83% versus 62%, P = 0.02), and more MULT+LONG patients had an orthopedic operation (35% versus 15%, P = 0.03). There was no difference in sepsis (41% versus 42%, P = 1.0), organ failures (37% versus 50%, P = 0.18), mortality (7% versus 12%, P = 0.52), ICU stay (14 +/- 2.5 versus 16 +/- 2 days, P = 0.57), hospital stay (26 +/- 3 versus 28 +/- 2 days, P = 0.53), or any other outcome parameter. Independent risk factors for sepsis were blunt mechanism of trauma, Injury Severity Score > or = 25, and more than two units of blood transfused over the first 24 hours, but not the amount of prophylactic antibiotics given. In conclusion, we found that 24-hour prophylaxis with a single broad-antibiotic is as effective as prophylaxis for longer periods of time with multiple spectrum antibiotics for critically injured patients at high risk for sepsis.


Examining the Effect of Chamomile on Clinical Symptoms and Hormonal Parameters Among Patients With Polycystic Ovarian Syndrome.
Polycystic ovarian syndrome is the most common cause of infertility and endocrine disorder among women due to anovulation. The aim of the present study is to investigate the effect of chamomile on oligomenorrhea and hirsutism symptoms as well as hormonal parameters among patients suffering from polycystic ovarian syndrome. The present study is a randomized clinical trial performed on 70 patients with diagnosis of polycystic ovarian syndrome according to Rotterdam criteria referring to the infertility clinic of a university hospital. The patients were randomly assigned into intervention and control groups, with the former receiving two chamomile capsules 500 mg for three months, and the latter receiving two placebo capsules for 3 months. Both groups were evaluated in terms of laboratory parameters (FBS, LDL, and testosterone) on the third day of first and third cycles. The collected data were analyzed by SPSS 20. The mean age, body mass index, marital status, history of infertility, and pregnancy rate showed no significant difference between the two groups. In the chamomile group, clinical symptoms of hirsutism (p<0.001) and oligomenorrhea (p=0.048) decreased following the treatment, but significant difference was found between the two groups only in hirsutism symptoms (p=0.028). Regarding the parameters of FBS (p=0.06), HDL (p=0.224), cholesterol (p=0.99), triglyceride (p=0.106), testosterone (p=0.894), and LDL (p=0.61), no significant difference was observed between the two groups. Nevertheless, following the treatment, testosterone decreased in both placebo (p=0.005) and chamomile (p=0.001) groups. overall, the chamomile therapeutic regimen has relatively been able to mitigate the clinical symptoms and testosterone levels in patients suffering from polycystic ovarian syndrome. Use of chamomile plant as a simple, inexpensive, and effective measure can be suggested for improving and treating patients with PCOS after confirmation by further studies.


Congenital infantile myofibroma causing intrauterine death in a twin.
While infantile myofibromatosis is the most common mesenchymal tumour of infancy, only around 300 cases have been reported. The authors report a 33-year-old para 1 with an uncomplicated, dichorionic diamniotic twin pregnancy who was diagnosed with an intrauterine death of one twin at 36+5 weeks gestation. At caesarean section, a macerated male stillborn weighing 2.72 kg was delivered. Postmortem examination revealed a pedunculated lesion attached to the left shoulder and underlying muscle consistent with a congenital myofibroma. The cause of death was postulated to be haemorrhage from the tumour surface causing fetal anaemia.


Zinc Oxide Nanoparticles Blunt Potassium-Bromate-Induced Renal Toxicity by Reinforcing the Redox System.
Potassium bromate (PB) is a general food additive, a significant by-product during water disinfection, and a carcinogen (Class II B). The compound emits toxicity depending on the extent of its exposure and dose through consumable items. The current study targeted disclosing the ameliorative efficacy of zinc oxide nanoparticles (ZnO NPs) prepared by green technology in PB-exposed Swiss albino rats. The rats were separated into six treatment groups: control without any treatment (Group I), PB alone (Group II), ZnO alone (Group III), ZnO NP alone (Group IV), PB + ZnO (Group V), and PB + ZnO NPs (Group VI). The blood and kidney samples were retrieved from the animals after following the treatment plan and kept at -20 °C until further analysis. Contrary to the control (Group I), PB-treated rats (Group II) exhibited a prominent trend in alteration in the established kidney function markers and disturbed redox status. Further, the analysis of the tissue and nuclear DNA also reinforced the biochemical results of the same treatment group. Hitherto, Groups III and IV also showed moderate toxic insults. However, Group VI showed a significant improvement from the PB-induced toxic insults compared to Group II. Hence, the present study revealed the significant therapeutic potential of the NPs against PB-induced nephrotoxicity in vivo, pleading for their usage in medicines having nephrotoxicity as a side effect or in enhancing the safety of the industrial use of PB.


[Optimal management of blood glucose levels in neurocritical patients].
To review the most significant studies on the pathophysiology of hypoglycaemia and hyperglycaemia in neurocritical patients and the therapeutic interventions used to control them. Available evidence shows that hypoglycaemia and hyperglycaemia increase brain injury and aggravate the prognosis, but it fails to establish the most suitable levels of blood glucose. Intensive treatment with insulin, compared with more moderate regimes, has not improved the prognosis and leads to further episodes of hypoglycaemia. Hypoglycaemia must always be avoided. Intensive treatment to control hyperglycaemia does not offer any kind of advantages and increases the likelihood of hypoglycaemia; it therefore cannot be recommended in neurocritical patients. No evidence is available showing the optimal level of blood glucose or the most suitable insulin regime, although its use is generally indicated when blood glucose levels are higher than 180-200 mg/dL. The value of the pharmacological control of blood glucose levels to improve the prognosis remains uncertain.


Segmental cable modelling of electrotonic transfer properties of deep superior colliculus neurons in the cat.
A segmental cable model of tecto-reticulo-spinal neurons of cat superior colliculus was constructed, based on detailed anatomical measurements from three neurons. The calculated membrane resistance for which the model best fitted the measured input resistance was 2,300-3,000 omega cm2. Electrotonic length of dendrites fell under 0.59-1.20 and 0.52-1.05 length constants, while the mean electrotonic length for the three cells averaged 0.91, 0.79, 0.81 and 0.80, 0.70, 0.71 (for sealed-end and open-end cable termination, respectively). Dendrite-to-soma conductance ratios averaged 16.0, 10.7, 7.5 and 21.3, 14.1, 11.4 for the two different end conditions, respectively. Synaptic efficacy was estimated by the transfer of steady-state voltage or current reaching the soma from distal dendritic locations. While voltage transfer was less than 1%, almost 60% of injected current (or charge) reached the soma. Analysis of voltage transients recorded experimentally in TRSNs demonstrated considerable difference between parameters derived from either equivalent-cylinder model or segmental cable model. The obvious deviations of TRSNs both in anatomical and electrotonic respect from the assumptions of the equivalent-cylinder model indicate that the detailed cable model will give a more appropriate description of these neurons. The significance of the estimated electrotonic parameters for the particular burst generation mechanism of TRSNs is discussed.


Recent Advances and the Potential for Clinical Use of Autofluorescence Detection of Extra-Ophthalmic Tissues.
The autofluorescence (AF) characteristics of endogenous fluorophores allow the label-free assessment and visualization of cells and tissues of the human body. While AF imaging (AFI) is well-established in ophthalmology, its clinical applications are steadily expanding to other disciplines. This review summarizes clinical advances of AF techniques published during the past decade. A systematic search of the MEDLINE database and Cochrane Library databases was performed to identify clinical AF studies in extra-ophthalmic tissues. In total, 1097 articles were identified, of which 113 from internal medicine, surgery, oral medicine, and dermatology were reviewed. While comparable technological standards exist in diabetology and cardiology, in all other disciplines, comparability between studies is limited due to the number of differing AF techniques and non-standardized imaging and data analysis. Clear evidence was found for skin AF as a surrogate for blood glucose homeostasis or cardiovascular risk grading. In thyroid surgery, foremost, less experienced surgeons may benefit from the AF-guided intraoperative separation of parathyroid from thyroid tissue. There is a growing interest in AF techniques in clinical disciplines, and promising advances have been made during the past decade. However, further research and development are mandatory to overcome the existing limitations and to maximize the clinical benefits.


A local contracted treatment of single and double excitations.
Starting from localized bond or lone-pair Hartree-Fock molecular orbitals, one may define contracted doubly excited functions for each pair of bond molecular orbitals. These functions are obtained from local single- and double-configuration interaction (CISD) of moderate size. Then one may build a contracted CISD matrix for the whole molecule, spanned by the Hartree-Fock determinant and these contracted doubly excited functions, the number of which is indeed moderate, as scaling at most as the square of the number of bonds. The calculation of the off-diagonal elements of this matrix is straightforward. Its diagonalization provides an upper bound to the lowest CISD eigenvalue. The well-known size-consistency error may be overcome through self-consistent dressings such as coupled-electron pair approximations, and cutoff criteria will lead to linear scaling. Numerical tests on a series of covalent and ionic systems show that the results are very close to that of coupled-cluster calculations. Possible improvements of this already efficient algorithm are suggested.


Acute diarrhea.
Acute diarrhea can be life-threatening in the very young, the elderly and the malnourished. Osmotic diarrhea is produced by unabsorbed solutes in the intestinal lumen, while exudative diarrhea is caused by infection and inflammation. Secretory diarrhea results from enterotoxins, oversecretion of gastrointestinal hormones and the action of bile acids. Rapid intestinal transit also may cause diarrhea.


Zebrafish cyclin-dependent protein kinase-like 1 (zcdkl1): identification and functional characterization.
The cyclin-dependent protein kinase family regulates a wide range of cellular functions such as cell cycle progression, differentiation, and apoptosis. In this study, we identified a zebrafish cyclin-dependent protein kinase-like 1 protein called zebrafish cdkl1 (zcdkl1), which shared a high degree of homology and conserved synteny with mammalian orthologs. zcdkl1 exhibited abilities for phosphorylation of myelin basic protein and histone H1. RT-PCR analysis revealed that zcdkl1 was expressed starting from fertilization and continuing thereafter. In adult tissues, zcdkl1 was predominantly detected in brain, ovary, and testis, and was expressed at low levels in other tissues. At 50% epiboly stage, zcdkl1 was widely expressed. At 12 to 48 h post-fertilization, zcdkl1 was predominantly expressed in the hypochord, the medial and lateral floor plate, and the pronephric duct. Interference of zcdkl1 expression resulted in abnormalities, such as brain and eye malformation, pericardial edema, and body axis curvature. Disruption of zcdkl1 reduced neurogenin-1 in the brain and sonic hedgehog expression in the floor plate region. These deformities were apparently rescued by co-injection of zcdkl1 mRNA. Findings of this study indicate that zcdkl1 plays an essential role in zebrafish development.


Modeling human lung development and disease using pluripotent stem cells.
Directed differentiation of human pluripotent stem cells (hPSCs) into mature cells, tissues and organs holds major promise for the development of novel approaches in regenerative medicine, and provides a unique tool for disease modeling and drug discovery. Sometimes underappreciated is the fact that directed differentiation of hPSCs also provides a unique model for human development, with a number of important advantages over model organisms. Here, I discuss the importance of using human stem cell models for understanding human lung development and disease.


Phenotyping chickpeas and pigeonpeas for adaptation to drought.
The chickpea and pigeonpea are protein-rich grain legumes used for human consumption in many countries. Grain yield of these crops is low to moderate in the semi-arid tropics with large variation due to high GxE interaction. In the Indian subcontinent chickpea is grown in the post-rainy winter season on receding soil moisture, and in other countries during the cool and dry post winter or spring seasons. The pigeonpea is sown during rainy season which flowers and matures in post-rainy season. The rainy months are hot and humid with diurnal temperature varying between 25 and 35°C (maximum) and 20 and 25°C (minimum) with an erratic rainfall. The available soil water during post-rainy season is about 200-250 mm which is bare minimum to meet the normal evapotranspiration. Thus occurrence of drought is frequent and at varying degrees. To enhance productivity of these crops cultivars tolerant to drought need to be developed. ICRISAT conserves a large number of accessions of chickpea (>20,000) and pigeonpea (>15,000). However only a small proportion (<1%) has been used in crop improvement programs mainly due to non-availability of reliable information on traits of economic importance. To overcome this, core and mini core collections (10% of core, 1% of entire collection) have been developed. Using the mini core approach, trait-specific donor lines were identified for agronomic, quality, and stress related traits in both crops. Composite collections were developed both in chickpea (3000 accessions) and pigeonpea (1000 accessions), genotyped using SSR markers and genotype based reference sets of 300 accessions selected for each crop. Screening methods for different drought-tolerant traits such as early maturity (drought escape), large and deep root system, high water-use efficiency, smaller leaflets, reduced canopy temperature, carbon isotope discrimination, high leaf chlorophyll content (drought avoidance), and breeding strategies for improving drought tolerance have been discussed.


Glutamatergic dysbalance and oxidative stress in in vivo and in vitro models of psychosis based on chronic NMDA receptor antagonism.
The psychotomimetic effects of N-methyl-D-aspartate (NMDA) receptor antagonists in healthy humans and their tendency to aggravate psychotic symptoms in schizophrenic patients have promoted the notion of altered glutamatergic neurotransmission in the pathogenesis of schizophrenia. The NMDA-receptor antagonist MK-801 was chronically administered to rats (0.02 mg/kg intraperitoneally for 14 days). In one subgroup the antipsychotic haloperidol (1 mg/kg) was employed as a rescue therapy. Glutamate distribution and 3-NT (3-nitrotyrosine) as a marker of oxidative stress were assessed by immunohistochemistry in tissue sections. In parallel, the effects of MK-801 and haloperidol were investigated in primary embryonal hippocampal cell cultures from rats. Chronic NMDA-R antagonism led to a marked increase of intracellular glutamate in the hippocampus (126.1 +/- 10.4% S.E.M of control; p=0.037), while 3-NT staining intensity remained unaltered. No differences were observed in extrahippocampal brain regions. Essentially these findings could be reproduced in vitro. The combined in vivo and in vitro strategy allowed us to assess the implications of disturbed glutamate metabolism for the occurrence of oxidative stress and to investigate the effects of antipsychotics. Our data suggest that oxidative stress plays a minor role in this model than previously suggested. The same applies to apoptosis. Moreover, the effect of haloperidol seems to be mediated through yet unidentified mechanisms, unrelated to D2-antagonism. These convergent lines of evidence indicate that further research should be focused on the glutamatergic system and that our animal model may provide a tool to explore the biology of schizophrenia.


Changes of dental treatment pattern in Norway in the 1970s.
With the aim of gauging utilization rates of dental services, a series of cross-sectional studies were performed in 1973, 1975 adnd 1977. Cluster samples of 1,600 individuals covering the Norwegian population aged 15 and above were interviewed by trained interviewers using standardized questions. The percentage of respondents who reported having seen a dentist within the last 12 months increased from 58 to 64. The receipt of tooth fillings was the predominant course of treatment and was reported by 55% of the interviewees. The percentage reporting preventive services increased from 15 to 26% at the expense of those reporting "blood and vulcanite" denistry. Fifty-two percent, increasing to 53% of the interviewers, claimed to have seen a dentist on a regular basis during the last 5 years. However, this proportion was conceivably overreported. Control questions indicated that 40-45% should be considered regular treatment attenders. Change is apparently taking place in the treatment pattern. The proportion of regular treatment attenders seems to increase by 0.5-1% per year. The treatment profile is also shifting: extractions and denture services are diminishing, preventive services are gaining, while restorative dentistry stands still - for the time being.


Direct insulin and leptin action on pro-opiomelanocortin neurons is required for normal glucose homeostasis and fertility.
Circulating leptin and insulin convey information regarding energy stores to the central nervous system, particularly the hypothalamus. Hypothalamic pro-opiomelanocortin (POMC) neurons regulate energy balance and glucose homeostasis and express leptin and insulin receptors. However, the physiological significance of concomitant leptin and insulin action on POMC neurons remains to be established. Here, we show that mice lacking both leptin and insulin receptors in POMC neurons (Pomc-Cre, Lepr(flox/flox) IR(flox/flox) mice) display systemic insulin resistance, which is distinct from the single deletion of either receptor. In addition, Pomc-Cre, Lepr(flox/flox) IR(flox/flox) female mice display elevated serum testosterone levels and ovarian abnormalities, resulting in reduced fertility. We conclude that direct action of insulin and leptin on POMC neurons is required to maintain normal glucose homeostasis and reproductive function.


At how many histocompatibility loci do congenic mouse strains differ? Probability estimates and some implications.
An expression is derived for the probability that a congenic strain and its inbred partner will differ by multiple linked histocompatibility genes when the number of incompatibilities between the original donor and background strains is known and the number of backcrosses to produce the strain is specified. This probability is shown to be rather large for typical values of the pertinent variables. Potential complications in data interpretation arising from unsuspected multiple incompatibilities between a congenic pair are discussed in relation to antigenic strength, H-locus polymorphism tissue distribution of H antigens, and certain types of experiments in which the cell-mediated lympholysis assay is used.


Is the growth-hormone response to insulin due to hypoglycaemia, hyperinsulinaemia or a fall in plasma free fatty acids?
Seven normal male volunteers were given a 2 h intravenous infusion of insulin (2 mu kg-1 min-1). During the first hour, in which nomoglycaemia was maintained by glucose infusion, no detectable increase in growth hormone (GH) secretion occurred. When controlled symptomatic hypoglycaemia was produced during the second hour of the insulin infusion a brisk rise in plasma GH concentration was observed in all the subjects studied. Since it was possible that the falls in the concentration of plasma free fatty acids (FFA) occurring during infusion of insulin also acted as a stimulus to GH release the study was repeated in four subjects but normoglycaemia was maintained throughout the entire 2 h period of insulin infusion. In these experiments there was no rise in plasma GH concentration although a similar fall in plasma FFA was produced. These results clearly indicate that hypoglycaemia per se was the important stimulus to GH secretion and not hyperinsulinaemia or a lowering of plasma FFA. Furthermore there appeared to be a threshold hypoglycaemic stimulus to GH secretion. In no subject was a rise in plasma GH seen without a fall in plasma glucose greater than 1.4 mmol/l. Prolonged mild hypoglycaemia did not stimulate GH secretion.


Group cognitive-behavioral therapy versus sertraline for the treatment of children and adolescents with obsessive-compulsive disorder.
To compare the effectiveness of group cognitive-behavioral therapy (GCBT) and of sertraline in treatment-naïve children and adolescents with obsessive-compulsive disorder. Between 2000 and 2002, 40 subjects between 9 and 17 years old were randomized to receive GCBT (n = 20) or sertraline (n = 20). GCBT consisted of a manual-based 12-week cognitive-behavioral protocol adapted for groups, and treatment with sertraline involved medication intake for 12 weeks. Subjects were assessed before, during, and after treatment (at 1, 3, 6, and 9 months after treatment conclusion). Primary outcome measure was the Children's Yale-Brown Obsessive-Compulsive Scale. Repeated-measures analyses of variance were done. Both GCBT and sertraline conditions had significant improvement in obsessive-compulsive disorder symptoms as measured by the Children's Yale-Brown Obsessive-Compulsive Scale after 12 weeks of treatment. After the 9-month follow-up period, subjects in the GCBT condition had a significantly lower rate of symptom relapse than those in the sertraline group. The treatment with GCBT may be effective in decreasing obsessive-compulsive symptoms in childhood obsessive-compulsive disorder and should be considered as an alternative to either individual cognitive-behavioral therapy or a medication, such as sertraline. Results support the effectiveness and the maintenance of gains of GCBT in the treatment of youngsters with obsessive-compulsive disorder.


Genetic therapy.
Vascular gene transfer is the introduction of foreign DNA into host cells within the vessel wall. Expression of recombinant genes within vascular cells has been demonstrated in normal, injured and atherosclerotic arteries. Transfer of genes with biological activity has provided insights into the role of specific genes in normal and pathological states. The development of gene transfer as a form of vascular therapy will require safe and effective vectors and intravascular delivery systems. Viral and non-viral vectors and several delivery catheters are being evaluated to determine their clinical applicability. The current applications of vascular gene transfer to cardiovascular diseases are the prevention of restenosis following arterial injury and induction of angiogenesis in occlusive vascular disease.


A novel mouse model of advanced diabetic kidney disease.
Currently available rodent models exhibit characteristics of early diabetic nephropathy (DN) such as hyperfiltration, mesangial expansion, and albuminuria yet features of late DN (hypertension, GFR decline, tubulointerstitial fibrosis) are absent or require a significant time investment for full phenotype development. Accordingly, the aim of the present study was to develop a mouse model of advanced DN with hypertension superimposed (HD mice). Mice transgenic for human renin cDNA under the control of the transthyretin promoter (TTRhRen) were employed as a model of angiotensin-dependent hypertension. Diabetes was induced in TTRhRen mice through low dose streptozotocin (HD-STZ mice) or by intercrossing with OVE26 diabetic mice (HD-OVE mice). Both HD-STZ and HD-OVE mice displayed more pronounced increases in urinary albumin levels as compared with their diabetic littermates. Additionally, HD mice displayed renal hypertrophy, advanced glomerular scarring and evidence of tubulointerstitial fibrosis. Both HD-OVE and HD-STZ mice showed evidence of GFR decline as FITC-inulin clearance was decreased compared to hyperfiltering STZ and OVE mice. Taken together our results suggest that HD mice represent a robust model of type I DN that recapitulates key features of human disease which may be significant in studying the pathogenesis of DN and in the assessment of putative therapeutics.


Epidemiology of dermatofibrosarcoma protuberans in Alberta, Canada, from 1988 to 2007.
There have only been a few population-based, epidemiologic studies assessing dermatofibrosarcoma protuberans (DFSP). To assess the epidemiology of DFSP in Alberta, Canada, over a 20-year period. A population-based, retrospective analysis of all cases of DFSP in Alberta was conducted using data from the Alberta Cancer Registry. Sex-, age-, and anatomical location-specific incidence rates and trends were determined. The overall age-standardized incidence rate of DFSP remained stable at 0.93 per 100,000. DFSP prevalence was highest in individuals aged 20 to 39 (46.8%), followed by those aged 40 to 59 (34.0%), 60 and older (14.7%), and lastly younger than 20 (4.5%). The mean age at diagnosis was 41.1 (women) and 43.1 (men). The incidence of DFSP in men and women has shown a dramatic shift such that incidence in women has increased 3.2% per year, whereas in men it has decreased 2.7% per year. In women, DFSP incidence increased on the trunk and decreased on the upper extremities. The age-standardized incidence of DFSP observed is nearly twice as high as previously reported and has remained stable. The incidence is increasing in women and decreasing in men. DFSP primarily affects young to middle-aged adults and most commonly presents on the trunk.


[Effect of BuYangHuanWu recipe on cerebral microcirculation in gerbils with ischemia-reperfusion].
To explore the protective mechanism of BuYangHuanWu recipe on neurofunction in gerbils with cerebral ischemia- reperfusion. Gerbils (n = 48) were divided randomly into three groups: animal model group, BuYangHuanWu recipe group, and sham control group. The animal model of cerebral ischemia was established using bilateral common carotid artery occlusion followed by unclamp 45 min after occlusion. The microcirculation was observed with a Laser Doppler. The density of microvascular was measured using Tannic acid ferric chloride mordant dyeing. The BBB (blood brain barrier) permeability was assessed using evan's blue (EB) dye. The water content in brain tissues was tested with wet and dry method. The learning and memory function test was performed with a 4-PTT dry path maze. Compared with the animal model group, BuYangHuanWu recipe increased blood flow in the hippocampal region at 1 and 5 min after occlusion, inhibited hypoperfusion at 15 min after reperfusion, increased blood flow at 30, 60 and 120 min after reperfusion. Meanwhile, BuYangHuanWu recipe inhibited the increase of BBB permeability and water content in brain tissues after reperfusion (P < 0.05). BuYangHuanWu recipe also improved the scores of learning and memory function of the gerbils. BuYangHuanWu recipe protects the neurofunction in gerbils with ischemia-reperfusion through modulating cerebral microcirculation damages.


Spirograterpene A, a Tetracyclic Spiro-Diterpene with a Fused 5/5/5/5 Ring System from the Deep-Sea-Derived Fungus Penicillium granulatum MCCC 3A00475.
A novel spiro-tetracyclic diterpene, spirograterpene A (1), was isolated from the deep-sea-derived fungus Penicillium granulatum MCCC 3A00475, together with two biosynthetically related cyclopianes, conidiogenone I (2) and conidiogenone C (3). The relative configuration of 1 was elucidated by extensive spectroscopic analyses, and the absolute structure was established by the modified Mosher's method. Compound 1 is the second example of a diterpene featuring a 5/5/5/5 spirocyclic carbon skeleton. It showed modest antiallergic activity.


Phosphine-functionalized NHC Ni(ii) and Ni(0) complexes: synthesis, characterization and catalytic properties.
Two families of nickel complexes bearing chelating diphenylphosphine-functionalized NHC ligands [NiII(ArNHCPPh2)(allyl)]Cl 1a (Ar = Mes); 1b, (Ar = 2,6-iPr2-C6H3) and [Ni0(ArNHCPPh2)(alkene)] 2a (Ar = 2,6-iPr2-C6H3, alkene = styrene); 2b (Ar = 2,6-iPr2-C6H3, alkene = diethyl fumarate) have been prepared and fully characterized. VT-NMR experiments in solution reveal that the allyl derivatives 1a-b are stereochemically nonrigid. The solid-state structure of the Ni0 derivative 2b is also reported. These complexes display interesting catalytic properties in various cross-coupling reactions. The precatalyst [Ni0(ArNHCPPh2)(styrene)] 2a was found to be the most active system. The bulkiness of the N-substituent on the imidazole ring and the low oxidation state of the metal center in 2a accounted for its enhanced catalytic performance. This system catalyzed effectively the coupling of (hetero)aryl chlorides with a range of nucleophiles including Grignard reagents, boronic acids, secondary amines and indoles.


Turner syndrome with rapidly progressive puberty: a case report and literature review.
This report describes a clinically rare and atypical case of 46,X,idic(X)(q21.32)/45,X-type Turner syndrome with rapidly progressive puberty development. After 11 months of treatment with recombinant human growth hormone (rhGH), the child's height increased. After 18 months of treatment with rhGH, the child showed secondary sex characteristics. The child was followed up for 1 year after the appearance of the secondary sex characteristics, and regular menses were still present. This case indicates that modern molecular biology techniques should be used rationally to further investigate the existence of X-chromosome translocations and occult chimeras to prevent misdiagnosis.


Recurrent inner ear decompression sickness associated with a patent foramen ovale.
Isolated inner ear injuries occurring during shallow scuba dives are an uncommon manifestation of decompression sickness in recreational divers. We describe a patient who presented with the typical symptoms of inner ear involvement after 2 independent dives within the decompression limits. The diver reported symptoms of unilateral (right-sided) hearing loss, tinnitus, and vertigo after dives to 35 and 50 m. After treatment with hyperbaric oxygen, his symptoms completely resolved. To confirm the hypothesis of inner ear decompression sickness (IEDCS), we examined the patient for a right-to-left shunt by cranial Doppler ultrasound and found a patent foramen ovale. The existence of a patent foramen ovale is suspected to be a risk factor for developing neurological symptoms of decompression sickness. There was no evidence of any other risk factors, so we suggest that the relevant right-to-left shunt in our patient may have been the predisposing factor that caused the inner ear symptoms during his scuba dive.


[Left persisting, singular superior vena cava and pacemaker electrode implantation by right cephalic vein].
We are reporting on a case of a singular left upper vena cava with an outlet into the right atrium by a large sinus coronarius (that means, the right vena cava is lacking totally). In spite of the well-known anomaly of the upper vena cava, we successfully implanted a stimulating electrode by the typical access through the right vena cephalica through the right sinus coronarius into the right ventricle. Except of a thrombosis of the rightsided deep venous system of the arm, no complications were to be complained within sixteen months. We know from literature, that within four more cases this transvenous access has been used in pacemaker-therapy. Various complications have been discussed. Before definately implanting an electrode, one should secure severely, if there is any special anomaly of the upper vena cava. In case of the here described, but very rare anomaly of the vana cava, it is to be examined thoroughly, whether an implantation of a transvenous electrode is indicated or, eventually, a myocardial implantation should be preferred.


Testing vision with angular and radial multifocal designs using Adaptive Optics.
Multifocal vision corrections are increasingly used solutions for presbyopia. In the current study we have evaluated, optically and psychophysically, the quality provided by multizone radial and angular segmented phase designs. Optical and relative visual quality were evaluated using 8 subjects, testing 6 phase designs. Optical quality was evaluated by means of Visual Strehl-based-metrics (VS). The relative visual quality across designs was obtained through a psychophysical paradigm in which images viewed through 210 pairs of phase patterns were perceptually judged. A custom-developed Adaptive Optics (AO) system, including a Hartmann-Shack sensor and an electromagnetic deformable mirror, to measure and correct the eye's aberrations, and a phase-only reflective Spatial Light Modulator, to simulate the phase designs, was developed for this study. The multizone segmented phase designs had 2-4 zones of progressive power (0 to +3D) in either radial or angular distributions. The response of an "ideal observer" purely responding on optical grounds to the same psychophysical test performed on subjects was calculated from the VS curves, and compared with the relative visual quality results. Optical and psychophysical pattern-comparison tests showed that while 2-zone segmented designs (angular & radial) provided better performance for far and near vision, 3- and 4-zone segmented angular designs performed better for intermediate vision. AO-correction of natural aberrations of the subjects modified the response for the different subjects but general trends remained. The differences in perceived quality across the different multifocal patterns are, in a large extent, explained by optical factors. AO is an excellent tool to simulate multifocal refractions before they are manufactured or delivered to the patient, and to assess the effects of the native optics to their performance.


Epidemiologic Analysis Along the Mevalonate Pathway Reveals Improved Cancer Survival in Patients Who Receive Statins Alone and in Combination With Bisphosphonates.
Cohort studies report associations between statin use and improved survival in patients with cancer. We used pharmacoepidemiologic methods to evaluate the survival of patients with cancer who received statins alone or in ostensibly synergistic drug combinations. Patients with cancer who were diagnosed from 2010 to 2013 were identified in a large health care claims database. The rate of all-cause death up to 1 year after diagnosis was compared by Cox proportional hazard regression. Sensitivity analyses included age stratification, statin type and intensity, and comparison with or without bisphosphonates and dipyridamole. Among 312,907 identified patients with cancer, treatment groups included statin users (n = 65,440), nonstatin users who received medications that block cholesterol absorption (n = 9,289), and nonusers (n = 226,007). Statin use before diagnosis was associated with improved overall survival compared with no treatment (hazard ratio [HR], 0.85; 95% CI, 0.80 to 0.91) and specifically in patients with leukemia, lung, or renal cancers. Nonstatin users had increased overall survival compared with no treatment (HR, 0.73; 95% CI, 0.62 to 0.85); when stratified, this difference held true only for pancreatic cancer and leukemia. No differences were observed between statin and nonstatin groups. Bisphosphonate use alone had no effect (n = 4,528), but patients who used both statins and bisphosphonates (n = 4,090) had increased survival compared with no treatment (HR, 0.60; 95% CI, 0.45 to 0.81). The effect of the combination of dipyridamole and statin use (n = 651) was not significant compared with no treatment. This study suggests that the combination of statins with drugs that affect isoprenylation, such as bisphosphonates, improves survival in patients with cancer. Consideration of pathway-specific pharmacology allows for hypotheses testing with the pharmacoepidemiologic approach. Prospective evaluation of these findings warrants clinical investigation and preclinical mechanistic studies.


[A cross-sectional study on physically violent behavior among youth males in Chengdu, Sichuan province].
To investigate the prevalence of physically violent behavior among 18-34 years old males in Chengdu. 2 151 males aged 18-34 years was recruited in Chengdu, using a multistage stratified random sampling method. "Men's health and modern lifestyles survey questionnaire" was adopted to collect information on demography, physical violent behavior, attitude and reactions to violence. Self-reported prevalence of physical violent behavior since 15 years of age among those 18-34 year-old males was 51.8%. 17.8% of the young males reported having violent behavior in the past 5 years, but the prevalence declined progressively with age (P < 0.01). People who were religious or remained single had higher prevalence rates than those non-religious, married or having regular sex partners (P < 0.01). Prevalence seemed relatively high in students or workers at service/commercial fields, with rates as 24.5% and 20.3%. Data from our study suggested that physical violence was an important problem among young males in Chengdu. Factors as being young, single, divorced or widowed were associated with self-reported violent behavior. People who were religious, being students or working at the service/commercial fields seemed to be under high risk of carrying physical violence.


Structural requirements for recognition of the HLA-Dw14 class II epitope: a key HLA determinant associated with rheumatoid arthritis.
Although HLA genes have been shown to be associated with certain diseases, the basis for this association is unknown. Recent studies, however, have documented patterns of nucleotide sequence variation among some HLA genes associated with a particular disease. For rheumatoid arthritis, HLA genes in most patients have a shared nucleotide sequence encoding a key structural element of an HLA class II polypeptide; this sequence element is critical for the interaction of the HLA molecule with antigenic peptides and with responding T cells, suggestive of a direct role for this sequence element in disease susceptibility. We describe the serological and cellular immunologic characteristics encoded by this rheumatoid arthritis-associated sequence element. Site-directed mutagenesis of the DRB1 gene was used to define amino acids critical for antibody and T-cell recognition of this structural element, focusing on residues that distinguish the rheumatoid arthritis-associated alleles Dw4 and Dw14 from a closely related allele, Dw10, not associated with disease. Both the gain and loss of rheumatoid arthritis-associated epitopes were highly dependent on three residues within a discrete domain of the HLA-DR molecule. Recognition was most strongly influenced by the following amino acids (in order): 70 greater than 71 greater than 67. Some alloreactive T-cell clones were also influenced by amino acid variation in portions of the DR molecule lying outside the shared sequence element.


Evaluation of a one-day AIDS continuing education course.
The effectiveness of a one-day acquired immune deficiency syndrome (AIDS) continuing education course for dentists and hygienists was evaluated using pretest, posttest, and six-month follow-up questionnaires. There was a general, though not statistically significant, increase in the percentage of respondents who reported they planned to be immunized against hepatitis B, and a statistically significant increase in dentists' perceptions of the percentage of their patients at risk for AIDS. The percentage of respondents who believed the private practice setting is the preferred practice site for treating healthy patients with human immunodeficiency virus (HIV) increased, though the increase was not statistically significant. Six-month follow-up results found a significant increase in the percentage of respondents who reported being immunized against hepatitis B. Other posttest results were maintained at the six-month follow-up. These results support the contention that a traditional lecture approach in AIDS continuing dental professional education can be beneficial.


Ethosuximide, sodium valproate or lamotrigine for absence seizures in children and adolescents.
Absence seizures are brief epileptic seizures which present in childhood and adolescence. They are characterised by sudden loss of awareness and an electroencephalogram (EEG) typically shows generalised spike wave discharges at three cycles per second. Ethosuximide, valproate and lamotrigine are currently used to treat absence seizures. This review aims to determine the best choice of anticonvulsant for a child with typical absence seizures. To review the evidence for the effects of ethosuximide, valproate and lamotrigine as treatments for children and adolescents with absence seizures, when compared with placebo or each other. We searched the Cochrane Epilepsy Group's Specialised Register (March 2005), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2005), MEDLINE (1966 to March 2005) and EMBASE (1988 to March 2005). No language restrictions were imposed. In addition, we contacted Sanofi Winthrop, Glaxo Wellcome (now GlaxoSmithKline) and Parke Davis (now Pfizer), manufacturers of sodium valproate, lamotrigine and ethosuximide respectively. Randomised parallel group monotherapy or add-on trials which include a comparison of any of the following in children or adolescents with absence seizures: ethosuximide; sodium valproate; lamotrigine or placebo. Outcome measures were: (1) proportion of individuals seizure free at 1, 3, 6, 12 and 18 months post randomisation; (2) people with a 50% or greater reduction in seizure frequency; (3) normalisation of EEG and/or negative hyperventilation test and (4) adverse effects. Data were independently extracted by two review authors. Results are presented as relative risks (RR) with 95% confidence intervals (95% CI). Five small trials were found, four of them were of poor methodological quality. One trial (29 participants) compared lamotrigine with placebo using a response conditional design. Individuals taking lamotrigine were significantly more likely to be seizure free than participants taking placebo during this short trial. Another trial compared lamotrigine with sodium valproate, the study lacked power to detect the difference in efficacy. Three studies compared ethosuximide, but because of diverse study designs and populations studied, we decided not to pool results in a meta-analysis. None of these studies found a difference between valproate and ethosuximide with respect to seizure control, but confidence intervals were wide and the existence of important differences could not be excluded. Although ethosuximide, lamotrigine and valproate are commonly used to treat people with absence seizures we have insufficient evidence to inform clinical practice, and the few trials included in this review were of poor methodological quality and did not have sufficient number of participants. More trials of better quality are needed.


A microfabricated lab-on-chip with three-dimensional electrodes for microscopic observation of bioelectromagnetic effects of cells.
Electromagnetic (EM) signals are widely used in electronic instruments and biomedical systems and might have affected the human bodies surrounded by them. However, the interaction mechanism of EM signals with biological structures is poorly understood. We propose a micro-fabricated low-frequency EM stimulation lab-on-chip with three-dimensional interdigital electrodes for observation of cell lines with microscope. The field strength between the electrodes at various frequencies is estimated through simulation. An electric field strength of 4.45Vrms/m is reached in the culture medium with a 10Vpp, 10 kHz input signal. According to the simulation results, the high end of the applicable frequency range of the testbench is 3 MHz. A prototype is fabricated using full-wafer microfabrication techniques. The impedance of the prototype between 20 Hz and 30 MHz is characterized. Moreover, human cell line HEK293T is cultured in the testbench for 24 h and observed using microscope to check the biocompatibility of the electrodes. The prototype is thus applicable to long-term microscopic observation of cell lines for study of EM effect on biological structures. The 24-h cell culturing experiment with and without EM stimulation with the proposed prototype shows that the cell growth is obviously affected by a 10 kHz EM signal.


Case Report: Culture-Dependent Postures in Japanese Patients With Schizophrenia.
Cross-cultural understanding of psychiatric symptoms is important in the current globalised society. Lack of knowledge regarding culture-dependent manifestations of psychiatric illnesses may lead to misjudgement by clinicians, resulting in inappropriate treatment. We present the cases of two patients with schizophrenia who showed Japanese-culture-dependent postures (seiza and dogeza). Seiza is a Japanese style of formal floor sitting. Dogeza includes bowing and touching the forehead to the floor while sitting in a kneeling position. When patients with schizophrenia perform these postures in a clinical setting, clinicians receive plenty of information regarding the patients' clinical states, including schizophrenia-related fear/tension, accusatory auditory verbal hallucinations, and pathological guilt.


Distal gastric bypass/duodenal switch procedure, Roux-en-Y gastric bypass and biliopancreatic diversion in a community practice.
Hybrid procedures combining purely restrictive and purely malabsorptive components to achieve stable long-term weight reduction have evolved since the 1970s. In a solo surgical community-based practice over the period 1984-1997, three different hybrid procedures were utilized as primary operations in patients who had not had prior bariatric surgery. Restrospective comparison of 32 patients who underwent biliopancreatic diversion (BPD), 138 patients who underwent distal gastric bypass Roux-en-Y (RGB) and 105 patients undergoing distal gastric bypass/duodenal switch procedure (DS) with 2-4 year follow-up in 37 DS patients. Height, initial weight and initial body mass index (BMI) were similar in the three groups. The DS patients were older. Mean BMI at 2 years fell from 49 to 29 kg/m2 in both DS and RGB. Mean percentage maximum preoperative weight lost was 40% in both the DS and RGB groups. Two-year mean percentage excess weight lost in DS was 78%, compared to 74% in RGB. There were no operative deaths and no ulcers in the DS group. DS is an important new option for primary treatment of morbid obesity. It can be performed safely, with up to 4 year follow-up showing stable weight loss.


Aeroelasticity-based fluid agitation for lab-on-chips.
In this study, we report a robust agitation method for small-volume liquids. It utilizes an elastic diaphragm as the bottom of a liquid chamber, upon which an initial tension is also applied to enhance the aeroelasticity effects at small/micro scales. As a result, spontaneous vibration of the diaphragm can be induced by an external air flow, which further provides fluid agitations. The device structure is simple and can be easily fabricated at low cost. More importantly, the vibration amplitude is controllable and varies widely from several tens to several hundred micrometers depending on the applied air pressure. The resulting agitation is effective and applicable at high viscosities of up to 900 cSt. The influences of air pressure and liquid viscosity on the vibration frequency are discussed. Potential applications of this technique for solid particle agitation, focusing and fluid mixing are also demonstrated.


Using occupancy models to understand the distribution of an amphibian pathogen, Batrachochytrium dendrobatidis.
Batrachochytrium dendrobatidis is a fungal pathogen that is receiving attention around the world for its role in amphibian declines. Study of its occurrence patterns is hampered by false negatives: the failure to detect the pathogen when it is present. Occupancy models are a useful but currently underutilized tool for analyzing detection data when the probability of detecting a species is <1. We use occupancy models to evaluate hypotheses concerning the occurrence and prevalence of B. dendrobatidis and discuss how this application differs from a conventional occupancy approach. We found that the probability of detecting the pathogen, conditional on presence of the pathogen in the anuran population, was related to amphibian development stage, day of the year, elevation, and human activities. Batrachochytrium dendrobatidis was found throughout our study area but was only estimated to occur in 53.4% of 78 populations of native amphibians and 66.4% of 40 populations of nonnative Rana catesbeiana tested. We found little evidence to support any spatial hypotheses concerning the probability that the pathogen occurs in a population, but did find evidence of some taxonomic variation. We discuss the interpretation of occupancy model parameters, when, unlike a conventional occupancy application, the number of potential samples or observations is finite.


Bereavement in paediatric intensive care.
The death of a child is a very sad event in anyone's life. It also affects all staff in paediatric intensive care units in different ways at different times. The publication of standards of bereavement care in paediatric intensive care hopes to be able to assist medical and nursing staff to understand and feel more confident in this emotionally difficult area of medicine. The aim of this article is to summarize some of the major points made in the document.


Synthesis of micellar-like terpolymer nanoparticles with reductively-cleavable cross-links and evaluation of efficacy in 2D and 3D models of triple negative breast cancer.
Triple negative or basal-like breast cancer (TNBC) is characterised by aggressive progression, lack of standard therapies and poorer overall survival rates for patients. The bad prognosis, high rate of relapse and resistance against anticancer drugs have been associated with a highly abnormal loss of redox control in TNBC cells. Here, we developed docetaxel (DTX)-loaded micellar-like nanoparticles (MLNPs), designed to address the aberrant TNBC biology through the placement of redox responsive cross-links designed into a terpolymer. The MLNPs were derived from poly(ethyleneglycol)-b-poly(lactide)-co-poly(N3-α-ε-caprolactone) with a disulfide linker pendant from the caprolactone regions in order to cross-link adjacent chains. The terpolymer contained both polylactide and polycaprolactone to provide a balance of accessibility to reductive agents necessary to ensure stability in transit, but rapid micellar breakdown and concomitant drug release, when in breast cancer cells with increased levels of reducing agents. The empty MLNPs did not show any cytotoxicity in vitro in 2D monolayers of MDA-MB-231 (triple negative breast cancer), MCF7 (breast cancer) and MCF10A (normal breast epithelial cell line), whereas DTX-loaded reducible crosslinked MLNPs exhibited higher cytotoxicity against TNBC and breast cancer cells which present high intracellular levels of glutathione. Crosslinked and non-crosslinked MLNPs showed high and concentration-dependent cellular uptake in monolayers and tumour spheroids, including when assessed in co-cultures of TNBC cells and cancer-associated fibroblasts. DTX loaded crosslinked MLNPs showed the highest efficacy against 3D spheroids of TNBC, in addition the MLNPs also induced higher levels of apoptosis, as assessed by annexin V/PI assays and increased caspase 3/7 activity in MDA-MB-231 cells in comparison to cells treated with DTX-loaded un-crosslinked MLNP (used as a control) and free DTX. Taken together these data demonstrate that the terpolymer micellar-like nanoparticles with reducible crosslinks have high efficacy in both 2D and 3D in vitro cancer models by targeting the aberrant biology, i.e. loss of redox control of this type of tumour, thus may be promising and effective carrier systems for future clinical applications in TNBC.


Development and validation of a search filter to identify equity-focused studies: reducing the number needed to screen.
Health inequalities, worse health associated with social and economic disadvantage, are reported by a minority of research articles. Locating these studies when conducting an equity-focused systematic review is challenging due to a deficit in standardised terminology, indexing, and lack of validated search filters. Current reporting guidelines recommend not applying filters, meaning that increased resources are needed at the screening stage. We aimed to design and test search filters to locate studies that reported outcomes by a social determinant of health. We developed and expanded a 'specific terms strategy' using keywords and subject headings compiled from recent systematic reviews that applied an equity filter. A 'non-specific strategy' was compiled from phrases used to describe equity analyses that were reported in titles and abstracts, and related subject headings. Gold standard evaluation and validation sets were compiled. The filters were developed in MEDLINE, adapted for Embase and tested in both. We set a target of 0.90 sensitivity (95% CI; 0.84, 0.94) in retrieving 150 gold standard validation papers. We noted the reduction in the number needed to screen in a proposed equity-focused systematic review and the proportion of equity-focused reviews we assessed in the project that applied an equity filter to their search strategy. The specific terms strategy filtered out 93-95% of all records, and retrieved a validation set of articles with a sensitivity of 0.84 in MEDLINE (0.77, 0.89), and 0.87 (0.81, 0.92) in Embase. When combined (Boolean 'OR') with the non-specific strategy sensitivity was 0.92 (0.86, 0.96) in MEDLINE (Embase 0.94; 0.89, 0.97). The number needed to screen was reduced by 77% by applying the specific terms strategy, and by 59.7% (MEDLINE) and 63.5% (Embase) by applying the combined strategy. Eighty-one per cent of systematic reviews filtered studies by equity. A combined approach of using specific and non-specific terms is recommended if systematic reviewers wish to filter studies for reporting outcomes by social determinants. Future research should concentrate on the indexing standardisation for equity studies and further development and testing of both specific and non-specific terms for accurate study retrieval.


Remembering proper names as a potential exception to the better-than-average effect in younger and older adults.
People see themselves as better than average in many domains, from leadership skills to driving ability. However, many people-especially older adults-struggle to remember others' names, and many of us are aware of this struggle. Our beliefs about our memory for names may be different from other information; perhaps forgetting names is particularly salient. We asked younger and older adults to rate themselves compared with others their age on several socially desirable traits (e.g., honesty); their overall memory ability; and their specific ability to remember scientific terms, locations, and people's names. Participants demonstrated a better-than-average (BTA) effect in their ratings of most items except their ability to remember names, which both groups rated as approximately the same as others their age. Older adults' ratings of this ability were related to a measure of the social consequences of forgetting another's name, but younger adults' ratings were not. The BTA effect is present in many judgments for both younger and older adults, but people may be more attuned to memory failures when those failures involve social consequences. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


[Prognosis of prune belly syndrome].
The Prune Belly syndrome (PBS) is unfrequent. Fourteen cases have been followed in our unit during the last 20 years. Four infants (29%) died during the first months of life, because of neonatal sepsis (2 cases) or end-stage renal failure (2 cases). Among the other 10 cases, 6 (43%) had normal glomerular filtration rate at a mean age of 10 years 6 months (6 months to 15 years), 4 had chronic renal failure, including 3 cases who developed end-stage renal failure at 8, 8 years 8 months and 17 years respectively. Resection of an urethral obstruction was performed in 2 cases. This surgical indication remains widely accepted, while the current tendency is to limit ureteral surgery in PBS. Orchidopexy was performed in 4 children, 3 of them less than 6 years 6 months of age. Fertility of these early operated children remains to be established, as all adults reported in the literature remain sterile when orchidopexy was not performed or was performed after age 6.


Experience with vasal sperm aspiration.
We describe our experience with vasal aspiration of sperm in patients with azoospermia secondary to neurogenic anejaculation or obstruction of the vas deferens. We performed 15 vasal sperm aspirations on 11 patients with neurogenic anejaculation or vasal obstruction. Adequate sperm was obtained from all 15 aspirations with an average sperm count of 42 x 10[6] (range 0.5 to 252 x 10[6]) and an average motility of 73.4% (range 16 to 100%). Aspirations were performed for use with assisted reproductive techniques in 12 cases and for cryopreservation alone in 3. Following assisted reproductive techniques 6 of the 12 aspirations (50%) resulted in pregnancy. Vasal aspiration of sperm should be considered when electroejaculation fails, is not available or is contraindicated. Although the overall sperm quality and pregnancy rate are higher with vasal aspiration and in vitro fertilization than electroejaculation and intrauterine insemination, vasal aspiration is a more technically demanding and costly approach to conception.


Multivariate analyses of immune markers reveal increases in plasma EN-RAGE in first-episode psychosis patients.
Immune cells and cytokines are largely recognized as significant factors in the pathophysiology of neuropsychiatric disorders. The possible role of other blood cells such as leukocytes in events of acute psychosis is in contrast only emerging. To study blood-born markers in acute psychosis we here evaluated plasma proteins in drug-naive first-episode psychosis (FEP) patients and healthy controls using a multiplex proximity extension assay technique. We analyzed a panel of 92 immune markers and plasma samples from 60 FEP patients and 50 controls and evaluated the changes obtained using multivariate statistical methods followed by protein pathway analyses. Data showed that 11 proteins are significantly different between FEP patients and healthy controls We observed increases in pro-inflammatory proteins such as interleukin-6, oncostatin-M, and transforming growth factor-alpha in FEP patients compared with controls. Likewise, the extracellular newly identified RAGE-binding protein (EN-RAGE) that regulates the expression of various cytokines was also elevated in the plasma of FEP patients. The results indicate that neutrophil-derived EN-RAGE could play an important role during the early phase of acute psychosis by stimulating cytokines and the immune response targeting thereby likely also the brain vasculature.


Thyroid hormones in milk: physiological approach--a review.
Reported values of the concentration of thyroid hormones in milk vary substantially. There are some doubts on the specificity of methods used for their estimation. We aimed, therefore, to study the effects of mother milk on thyroid function parameters in sucklings as well as at the effect of milk secretion on maternal thyroid. According to Fukuda et al. [1980] the lactation induces a hypothyroid state in the rat (high TSH, low thyroid hormones in maternal plasma). In our study the weaning of 18-day old rats resulted in gradual decrease of T4 in suckling plasma through 24 h followed with a transient thyroid activation. Thyroidectomy of lactating rats resulted in a transient decrease of T4 in sucklings. The difference in mother milk intake achieved by different litter size also affected the thyroid function of sucklings. The pups from small size litters (more milk consumption) had low thyroid secretion rate and low plasma TSH, while the level of T4 in plasma was high under a higher growth rate and accelerated overall maturation. All these results suggest an exogenous intake of thyroid hormones in suckling rat. We found that lactation in women resulted in lower T4 and higher TSH in plasma as compared to women who had interrupted their lactation. In the next part of our study more than 80 infants were longitudinally followed and sampled at birth (cord blood), at 2, 6 and 10 weeks and at 4, 6, 9 and 12 months. Only moderate differences were found at 4 months (high rT3) in breast fed infants and 9 at months (high T3 in plasma of infants weaned during the first week of life) when the data were evaluated according to the type of feeding. Thyroid activity of human milk was tested by feeding thyroidectomized rats with a diet containing human milk. Although plasma TSH was affected by such a diet, we did not detect any T4 and T3 in plasma of thyroidectomized rats which probably refects low calculated intake of hormones with the diet. We conclude that the lactation affects the thyroid economy of maternal organisms. Maternal milk definitely affects thyroid function parameters in the rat, while the effect on infant thyroid is more difficult to demonstrate.


Identification of the regulatory proteins in human pancreatic cancers treated with Trichostatin A by 2D-PAGE maps and multivariate statistical analysis.
In this paper, principal component analysis (PCA) is applied to a spot quantity dataset comprising 435 spots detected in 18 samples belonging to two different cell lines (Paca44 and T3M4) of control (untreated) and drug-treated pancreatic ductal carcinoma cells. The aim of the study was the identification of the differences occurring between the proteomic patterns of the two investigated cell lines and the evaluation of the effect of the drug Trichostatin A on the protein content of the cells. PCA turned out to be a successful tool for the identification of the classes of samples present in the dataset. Moreover, the loadings analysis allowed the identification of the differentially expressed spots, which characterise each group of samples. The treatment of both the cell lines with Trichostatin A therefore showed an appreciable effect on the proteomic pattern of the treated samples. Identification of some of the most relevant spots was also performed by mass spectrometry.


[Scrapie of sheep and Creutzfeldt-Jakob disease in Iceland].
Scrapie of sheep and Creutzfeldt-Jakob disease (CJD) are both classified as prion diseases. The infectious agents of both diseases are closely related. The objectives of the study was to explore, whether sheep scrapie could be transmitted to humans and cause CJD. The occurrence of CJD was studied in a period of 40 years, 1960 to 2000. The first part of the study, which was started in 1980, was retrospective. Hospital records from the Department of Neurology of the National Hospital from the years 1960-1980 were scrutinised and paraffin blocks from the collection of the Department of Pathology from cases with the diagnosis CJD and some suspect cases were obtained and analysed. The latter part of the study was prospective, which gave the possibility to study codon 129 of PRNP gene and characterise the strain of the infectious agent. Information on the epidemiology of scrapie in Iceland and of the diet of Icelanders was collected. Four cases of CJD were detected in the 40 years studied, which corresponds to an incidence of 0.44 per million inhabitants, which is less than half the average incidence in 18 other European countries in the years 1997-2004. The low incidence of CJD in Iceland does not indicate that sheep scrapie can be transmitted to humans and cause CJD. If this were the case, we would have expected an higher incidence of CJD and possibly atypical cases, as the Icelandic population has been exposed to scrapie for 130 years.


The sensory system: More than just a window to the external world.
While the traditional importance of the sensory system lies in its ability to perceive external information about the world, emerging discoveries suggest that sensory perception has a greater impact on health and longevity than was previously appreciated. These effects are conserved across species. In this mini-review, we discuss the specific sensory cues that have been identified to significantly impact organismal physiology and lifespan. Ongoing work in the aging field has begun to identify the downstream molecules that mediate the broad effects of sensory signals. Candidates include FOXO, neuropeptide F (NPF), adipokinetic hormone (AKH), dopamine, serotonin, and octopamine. We then discuss the many implications that arise from our current understanding of the effects of sensory perception on health and longevity.


Expanding the Link between Out-Group Threats and In-Group Behavior: (A Reply to Kavaliers and Choleris).
In social species, groups and their members face a variety of threats from conspecific outsiders. Such out-group conflict is predicted to influence within-group behavior, with empirical work demonstrating this link in humans, primates, and birds. In our note "Out-Group Threat Promotes Within-Group Affiliation in a Cooperative Fish," appearing in The American Naturalist in February 2016, we provided experimental evidence that simulated territorial intrusions result in subsequent increases in affiliation among groupmates in a cichlid fish (Neolamprologus pulcher). Martin Kavaliers and Elena Choleris, in their comment "Out-Group Threat Responses, In-Group Bias, and Nonapeptide Involvement Are Conserved Across Vertebrates," appearing in this issue, commented on our cichlid-fish article; they consider the conserved nature of the link between out-group threat and in-group behavior and bias in vertebrates, the influence of pathogens in the process, and the potential underpinning hormonal mechanisms. Here, we provide clarification and expansion of some of the core points that are discussed in the comment by Kavaliers and Choleris.