ABI4 regulates primary seed dormancy by regulating the biogenesis of abscisic acid and gibberellins in arabidopsis.
Seed dormancy is an important economic trait for agricultural production. Abscisic acid (ABA) and Gibberellins (GA) are the primary factors that regulate the transition from dormancy to germination, and they regulate this process antagonistically. The detailed regulatory mechanism involving crosstalk between ABA and GA, which underlies seed dormancy, requires further elucidation. Here, we report that ABI4 positively regulates primary seed dormancy, while negatively regulating cotyledon greening, by mediating the biogenesis of ABA and GA. Seeds of the Arabidopsis abi4 mutant that were subjected to short-term storage (one or two weeks) germinated significantly more quickly than Wild-Type (WT), and abi4 cotyledons greened markedly more quickly than WT, while the rates of germination and greening were comparable when the seeds were subjected to longer-term storage (six months). The ABA content of dry abi4 seeds was remarkably lower than that of WT, but the amounts were comparable after stratification. Consistently, the GA level of abi4 seeds was increased compared to WT. Further analysis showed that abi4 was resistant to treatment with paclobutrazol (PAC), a GA biosynthesis inhibitor, during germination, while OE-ABI4 was sensitive to PAC, and exogenous GA rescued the delayed germination phenotype of OE-ABI4. Analysis by qRT-PCR showed that the expression of genes involved in ABA and GA metabolism in dry and germinating seeds corresponded to hormonal measurements. Moreover, chromatin immunoprecipitation qPCR (ChIP-qPCR) and transient expression analysis showed that ABI4 repressed CYP707A1 and CYP707A2 expression by directly binding to those promoters, and the ABI4 binding elements are essential for this repression. Accordingly, further genetic analysis showed that abi4 recovered the delayed germination phenotype of cyp707a1 and cyp707a2 and further, rescued the non-germinating phenotype of ga1-t. Taken together, this study suggests that ABI4 is a key factor that regulates primary seed dormancy by mediating the balance between ABA and GA biogenesis.


Patterning of pH sensitive fluorescent bipyridazine derivatives.
A pH sensitive pipeprazine substituted bipyridazine fluorophore, DPP-BPDZ was explored as a pH sensor in solution and thin film state. Greenish highly fluorescent solution of the DPP-BPDZ with fluorescence quantum yield of 0.63 showed fluorescence decrease as the acetic acid concentration of the media was increased. The fluorescence quenching was correlated linearly with the content of acetic acid dose and attributed to the protonation at the terminal piperazine group. An acid sensitive film was fabricated using a transparent polymeric host (PMMA) and the DPP-BPDZ dye molecules as a guest. The resultant bright green fluorescent film (1.4 microm thick) showed exponential decrease of the fluorescence intensity as the pH of the dipping solution was decreased. In the range of pH below 4.5, the film sensitivity to pH was higher than the pH range over 4.5. A patternable film sensor was fabricated by introducing a photo acid generator (PAG) layer on the dye layer. Fluorescence patterns was formed on the film sensor through a photo-mask by relatively weak power of UV light (0.4 mW/cm2). Fluorescent line patterns having 10 microm line width were obtained with high fluorescence contrast between the patterns.


Brain and Myocardial Mitochondria Follow Different Patterns of Dysfunction After Cardiac Arrest.
Mitochondria is often considered as the common nexus of cardiac and cerebral dysfunction after cardiac arrest. Here, our goal was to determine whether the time course of cardiac and cerebral mitochondrial dysfunction is similar after shockable versus non-shockable cardiac arrest in rabbits. Anesthetized rabbits were submitted to 10 min of no-flow by ventricular fibrillation (VF group) or asphyxia (non-shockable group). They were euthanized at the end of the no-flow period or 30 min, 120 min, or 24 h after resuscitation for in vitro evaluation of oxygen consumption and calcium retention capacity. In the brain (cortex and hippocampus), moderate mitochondrial dysfunction was evidenced at the end of the no-flow period after both causes of cardiac arrest versus baseline. It partly recovered at 30 and 120 min after cardiac arrest, with lower calcium retention capacity and higher substrate-dependant oxygen consumption after VF versus non-shockable cardiac arrest. However, after 24 h of follow-up, mitochondrial dysfunction dramatically increased after both VF and non-shockable cardiac arrest, despite greater neurological dysfunction after the latter one. In the heart, mitochondrial dysfunction was also maximal after 24 h following resuscitation, with no significant difference among the causes of the cardiac arrest. During the earlier timing of evaluation, calcium retention capacity and ADP-dependant oxygen consumption were lower and higher, respectively, after non-shockable cardiac arrest versus VF. In conclusion, the kinetics of cardiac and cerebral mitochondrial dysfunction suggests that mitochondrial function does not play a major role in the early phase of the post-resuscitation process but is only involved in the longer pathophysiological events.


Exploration of a binding mode of indole amide analogues as potent histone deacetylase inhibitors and 3D-QSAR analyses.
Docking simulations and three-dimensional quantitative structure-activity relationship (3D-QSAR) analyses were conducted on a series of indole amide analogues as potent histone deacetylase inhibitors. The studies include comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). Selected ligands were docked into the active site of human HDAC1. Based on the docking results, a novel binding mode of indole amide analogues in the human HDAC1 catalytic core is presented, and enzyme/inhibitor interactions are discussed. The indole amide group is located in the open pocket, and anchored to the protein through a pair of hydrogen bonds with Asp99 O-atom and amide NH group on ligand. Based on the binding mode, predictive 3D-QSAR models were established, which had conventional r2 and cross-validated coefficient values (r(cv)2) up to 0.982 and 0.601 for CoMFA and 0.954 and 0.598 for CoMSIA, respectively. A comparison of the 3D-QSAR field contributions with the structural features of the binding site showed good correlation between the two analyses. The results of 3D-QSAR and docking studies validate each other and provided insight into the structural requirements for activity of this class of molecules as HDAC inhibitors. The CoMFA and CoMSIA PLS contour maps and MOLCAD-generated active site electrostatic, lipophilicity, and hydrogen-bonding potential surface maps, as well as the docking studies, provided good insights into inhibitor-HDAC interactions at the molecular level. Based on these results, novel molecules with improved activity can be designed.


[Intraneural ganglion of the common peroneal nerve. A clinical case report].
A case report of an intraneural ganglion of the common peroneal nerve is presented. Problems of differential diagnosis and therapy are discussed as well as some aspects of the etiology.


BET 1: Lidocaine with propofol to reduce pain on injection.
A short review was carried out to see if mixing lidocaine with propofol is a safe and effective method in reducing the commonly reported pain at the injection site. Four relevant papers were found using the described search strategy. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these papers are tabulated. Although a promising idea, a paucity of good quality evidence suggests further needed research.


X-linked spinal muscular atrophy in mice caused by autonomous loss of ATP7A in the motor neuron.
ATP7A is a copper-transporting P-type ATPase that is essential for cellular copper homeostasis. Loss-of-function mutations in the ATP7A gene result in Menkes disease, a fatal neurodegenerative disorder resulting in seizures, hypotonia and failure to thrive, due to systemic copper deficiency. Most recently, rare missense mutations in ATP7A that do not impact systemic copper homeostasis have been shown to cause X-linked spinal muscular atrophy type 3 (SMAX3), a distal hereditary motor neuropathy. An understanding of the mechanistic and pathophysiological basis of SMAX3 is currently lacking, in part because the disease-causing mutations have been shown to confer both loss- and gain-of-function properties to ATP7A, and because there is currently no animal model of the disease. In this study, the Atp7a gene was specifically deleted in the motor neurons of mice, resulting in a degenerative phenotype consistent with the clinical features in affected patients with SMAX3, including the progressive deterioration of gait, age-dependent muscle atrophy, denervation of neuromuscular junctions and a loss of motor neuron cell bodies. Taken together, these data reveal autonomous requirements for ATP7A that reveal essential roles for copper in the maintenance and function of the motor neuron, and suggest that SMAX3 is caused by a loss of ATP7A function that specifically impacts the spinal motor neuron.


Prognosis of mucinous histology for patients with radically resected stage II and III colon cancer.
Previous studies investigating the prognostic role of mucinous histology of colorectal cancer produced conflicting results. This retrospective analysis was carried out in order to explore whether mucinous adenocarcinoma (MC) is associated with a comparatively worse prognosis than that of nonmucinous adenocarcinoma (NMC) for patients undergoing curative resection for stage II and III colon cancer. This study involved 1025 unselected patients who underwent curative surgery for sporadic colon cancer and follow-up procedures at six different oncology departments. MCs accounted for 17.4% (n=178) of tumours. Patients with MC had 5- and 8-year overall survival rates of 78.6% and 68.8%, respectively, compared with 72.3% and 63.8%, respectively, for patients with nonmucinous tumours. Multivariate analysis using the Cox proportional hazards model showed that the clinically significant prognostic factors were stage of disease and adjuvant chemotherapy. No statistically significant interaction between mucinous histology and adjuvant chemotherapy was found. For patients with stage II and III colon cancer who underwent curative surgery, mucinous histology has no significant correlation with prognosis compared with NMC. This retrospective analysis suggests a comparable benefit from adjuvant chemotherapy for MC compared with NMC.


Absence of deterioration of vascular function of the donor limb at late follow-up after radial artery harvesting.
Radial artery harvesting has been questioned because of purported long-term circulatory consequences. Previous midterm Doppler ultrasonographic results are inconsistent regarding ulnar arterial effects. Flow-mediated vasodilatation more sensitively measures response to shear stress as index of arterial reactivity and function. We contacted 231 patients who had undergone radial artery harvesting at least 10 years previously (mean follow-up, 12.9 ± 0.8 years). Subcohort of 25 volunteers (mean age, 69.2 ± 8.4 years) underwent ultrasonographic evaluation of ipsilateral (harvest) and contralateral (control) ulnar arteries. Flow-mediated vasodilatation compared changes in ulnar arterial diameters before and after occlusion. In subcohort, peak systolic velocity of harvest ulnar artery was 0.82 ± 0.15 m/s, versus 0.63 ± 0.23 m/s on control side (P < .001), with no differences in intimomedial thickness (P = .763) or presence of atherosclerotic plaques (P = .364). Baseline diameter of harvest ulnar artery was 3.0 ± 0.5 mm, versus 2.7 ± 0.6 mm on control side (P = .007). Postocclusion diameter of harvest ulnar artery was 3.2 ± 0.5 mm, versus 2.9 ± 0.6 mm on control side (P = .001). No differences were seen in preocclusion and postocclusion absolute and percentage changes in ulnar arterial diameter (Table 1). Despite increased shear stress, no deterioration in either ulnar arterial structure or functional reactivity was measured by flow-mediated vasodilatation more than 10 years after radial artery harvesting. With appropriate preoperative evaluation, radial arterial grafting for coronary artery bypass grafting is not associated with long-term donor limb vascular insufficiency.


Mistletoe for cancer? A systematic review of randomised clinical trials.
Mistletoe extracts are widely used in the treatment of cancer. The results of clinical trials are however highly inconsistent. We therefore conducted a systematic review of all randomised clinical trials of this unconventional therapy. Eight databases were searched to identify all studies that met our inclusion/exclusion criteria. Data were independently validated and extracted by 2 authors and checked by the 3rd according to predefined criteria. Statistical pooling was not possible because of the heterogeneity of the primary studies. Therefore a narrative systematic review was conducted. Ten trials could be included. Most of the studies had considerable weaknesses in terms of study design, reporting or both. Some of the weaker studies implied benefits of mistletoe extracts, particularly in terms of quality of life. None of the methodologically stronger trials exhibited efficacy in terms of quality of life, survival or other outcome measures. Rigorous trials of mistletoe extracts fail to demonstrate efficacy of this therapy.


Autophagy in rat annulus fibrosus cells: evidence and possible implications.
Programmed cell death of intervertebral disc (IVD) cells plays an important role in IVD degeneration, but the role of autophagy, a closely related cell death event, in IVD cells has not been documented. The current study was designed to investigate the effect of interleukin (IL)-1β on the occurrence of autophagy of rat annulus fibrosus (AF) cells and the interrelationship between autophagy and apoptosis. Rat AF cells were isolated and exposed, in tissue cultures with or without serum, to IL-1β in different concentrations for 24 hours. Ultrastructural analysis, flow cytometry and lysosomal activity assessment were performed after the in vitro treatment to determine the presence and levels of autophagy. The mRNA expression of autophagy-related proteins (Beclin-1, Bcl-2 and microtubule associated protein 1 light chain 3 (LC3)) were evaluated using real-time PCR. 3-methyladenine (3-MA), a PI3K inhibitor, was used to determine the interaction between autophagy and apoptosis via the suppression of autophagy. Autophagy was detected in rat AF cells under serum starvation condition by transmission electron microscopy. PCR and flow cytometry results showed that IL-1β enhanced the autophagy-induction effect of serum deprivation in a dose-dependent manner. However, IL-1β alone failed to induce autophagy in AF cells cultured without serum starvation. When autophagy was suppressed by 3-MA, the apoptosis incidence was increased. Serum supplement also partly reversed the autophagy incidence without affecting the apoptosis incidence in the same cells. IL-1β up-regulates serum deprivation-induced autophagy of AF cells in a dose-dependent manner. Autophagy may represent a protective mechanism against apoptosis in AF cells and IVD degeneration.


[Morphofunctional characteristics of secretion-producing structures of the gastric and duodenal mucosa in liquidators of aftermaths of the Chernobyl accident with peptic ulcer of the duodenum].
With the aid of the comparative structural analysis of 145 biopsy specimens of the gastric and duodenal mucosa obtained from two groups of patients with peptic ulcer of the duodenum (liquidators of effects of the Chernobyl power plant accident and those subjects comprizing the control group), particular morphological features were revealed in the liquidators. These included the following: significant decline in parameters for parietal cells (mostly nuclei), striking alterable changes in their cytoplasma; transformation of the process of glycosylation of glycoproteins in the course of mucus production with disturbances of formation, excertion of the secretion and cytoprotective properties of the mucus; increase in the proliferative activity of the epithelium with insufficiency of cytodifferentiation and functional inadequacy.


Transport of vitamin B 12 in Escherichia coli.
The uptake of (60)Co-labeled cyanocobalamin (vitamin B(12)) by cells of Escherichia coli K-12lambda was shown to consist of an initial rapid phase (complete in <1 min), followed by a slower secondary phase. Methods enabling the measurement of (60)Co-B(12) uptake after incubation times of 1 to 2 sec were used in studies on the initial rate of B(12) uptake. This initial process showed saturation kinetics, with a V(max) of 56 molecules per sec per cell and a K(m) of 5 nm, and was essentially independent of cellular energy metabolism. No inhibition was obtained with cyanide, fluoride, arsenite, or 2, 4-dinitrophenol, and an energy of activation of 3.8 kcal/mole for this initial phase of uptake was calculated from its response to temperature changes between 15 and 35 C. The inhibition by HgCl(2) (50% at 0.1 mm) but not by 1 mmN-ethylmaleimide or 1 mmp-chloromercuribenzoate was consistent with a role for a relatively inaccessible sulfhydryl residue at the initial B(12) binding site. The secondary phase of B(12) uptake was clearly dependent on the energy metabolism of the cell, and, from its response to temperature, an energy of activation of about 17 kcal/mole was calculated. Cyanide (10 mm), arsenite (10 mm), and 2, 4-dinitrophenol (0.1 mm) gave at least 70% inhibition of the rate of the secondary phase. The formation of other cobalamins, such as 5'-deoxyadenosyl cobalamin, was not an obligate part of B(12) transport. The cells were also able to take up (60)Co-labeled cobinamide cyanide.


The novel latex agglutination turbidimetric immunoassay system for simultaneous measurements of calprotectin and hemoglobin in feces.
Fecal calprotectin (Fcal) as well as the fecal immunochemical test (FIT) are useful biomarkers for detecting activity and mucosal healing in inflammatory bowel diseases. Here, we report the performance of simultaneous measurements of Fcal and FIT for ulcerative colitis (UC) patients using the newly-developed latex agglutination turbidimetric immunoassay (LATIA) system. Fcal and hemoglobin were measured by the LATIA system in 152 UC patients who underwent colonoscopy. Fcal was also quantified with a conventional enzyme-linked immunosorbent assay (ELISA). Fecal markers were evaluated in conjunction with the mucosal status of UC, which was assessed via the Mayo endoscopic subscore (MES) classification. The LATIA system could quantify calprotectin and hemoglobin simultaneously with the same fecal samples within 10 minutes. The values of the Fcal-LATIA closely correlated with those of the Fcal-ELISA (Spearman rank correlation coefficient, r=0.84; P<0.0001). The values of Fcal for each assay and the FIT all significantly correlated with the MESs (Spearman rank correlation coefficient, Fcal-LATIA: r=0.58, Fcal-ELISA: r=0.55, and FIT: r=0.72). The mucosal healing predictability (determined by an MES of 0 alone) of the Fcal-LATIA, Fcal-ELISA, and FIT-LATIA with the cutoffs determined by receiver operating characteristic curve analysis was 0.79, 0.78, and 0.92 for sensitivity, respectively, and 0.78, 0.69, and 0.73 for specificity, respectively. The performance of the novel Fcal-LATIA was equivalent to that of the conventional Fcal assay. Simultaneous measurements with FITs would promote the clinical relevance of fecal biomarkers in UC.


Early-Onset Ovarian Cancer <30 Years: What Do We Know about Its Genetic Predisposition?
Ovarian cancer (OC) is one of the leading causes of cancer-related deaths in women. Most patients are diagnosed with advanced epithelial OC in their late 60s, and early-onset adult OC diagnosed ≤30 years is rare, accounting for less than 5% of all OC cases. The most significant risk factor for OC development are germline pathogenic/likely pathogenic variants (GPVs) in OC predisposition genes (including BRCA1, BRCA2, BRIP1, RAD51C, RAD51D, Lynch syndrome genes, or BRIP1), which contribute to the development of over 20% of all OC cases. GPVs in BRCA1/BRCA2 are the most prevalent. The presence of a GPV directs tailored cancer risk-reducing strategies for OC patients and their relatives. Identification of OC patients with GPVs can also have therapeutic consequences. Despite the general assumption that early cancer onset indicates higher involvement of hereditary cancer predisposition, the presence of GPVs in early-onset OC is rare (<10% of patients), and their heritability is uncertain. This review summarizes the current knowledge on the genetic predisposition to early-onset OC, with a special focus on epithelial OC, and suggests other alternative genetic factors (digenic, oligogenic, polygenic heritability, genetic mosaicism, imprinting, etc.) that may influence the development of early-onset OC in adult women lacking GPVs in known OC predisposition genes.


The unrecognised French BSE epidemic.
In France, implementation of systematic screening programs in 2000, as a complement to the mandatory reporting of animals with clinical signs of BSE (passive surveillance), revealed certain limitations of the mandatory system. Indeed, systematic screening showed that some BSE cases were not detected by the clinical surveillance system, implying considerable BSE case under-reporting throughout the epidemic. As the most likely explanation for variant Creutzfeldt-Jakob disease (vCJD) is exposure to the aetiologic agent of BSE, it is essential to reconstruct the French BSE epidemic pattern accounting for this under-reporting. We estimated age- and year-specific incidence rates of BSE by using a back-calculation method. This approach relies on the principle that the number of clinical BSE cases is the consequence of the number of BSE-infected animals after a known incubation time, defined as the time between infection and clinical onset. We generalized this model to take into account epidemiological characteristics of BSE, such as French cattle mortality, BSE case reporting probability, and age-dependent susceptibility and/or exposure to the BSE agent. We confirmed that the average BSE incubation period is five years and that the peak risk of bovine infection occurs between 6 and 12 months of age. The results also showed that the proportion of underreporting is the most influential parameter in the model, and that BSE was substantially underreported until rapid tests were introduced. Indeed, only 103 BSE cases were detected by passive surveillance up to June 2000, while we estimated that there was 301 200 (95% confidence interval (CI) [27 600-837 600]) cattle infected by the BSE agent. Despite uncertainty over the beginning of the epidemic, we showed that the French BSE epidemic in the late 1980s was completely undetected, and only the second wave, after 1990, was observed.


Topical steroids versus systemic antifungals in the treatment of chronic paronychia: an open, randomized double-blind and double dummy study.
The involvement of Candida in the pathogenesis of chronic paronychia (CP) has never been proven, even though this condition is commonly considered a type of Candida onychomycosis. The purpose of this study was to compare the efficacy of systemic antifungals (itraconazole or terbinafine) with a topical corticosteroid (methylprednisolone aceponate) in the treatment of patients with CP. The study involved 45 adult patients with CP. Medication was given in a randomized, double-blind and double dummy manner over 3 weeks. Patients were then followed for 6 weeks. Clinical and mycologic evaluations were performed at baseline, and at weeks 3 and 9. The efficacy measures included clinical and photographic evaluation. Of 48 nails treated with methylprednisolone aceponate, 41 were improved or cured at the end of the follow-up period. The statistical analysis showed a significant difference between the number of nails improved or cured by methylprednisolone aceponate and that of nails improved or cured with terbinafine (30 out of 57) or itraconazole (29 out of 64). Presence of Candida was not strictly linked to disease activity, and Candida eradication was associated with clinical cure in only 2 of the 18 patients who carried Candida at the beginning of the study. This study shows that topical steroids are more effective than systemic antifungals in the treatment of CP, and supports the view that CP is not a type of onychomycosis but a variety of hand dermatitis caused by environmental exposure.


The complete plastome of tropical fruit Garcinia mangostana (Clusiaceae).
The complete plastome sequence of Garcinia mangostana L. (Clusiaceae) is completed in this study (NCBI acc. no. KX822787). This is a first complete plastome sequence from the Clusiaceae. The complete plastome size is 158,179 bp in length and consists of a large single copy of 86,458 bp and a small single copy of 17,703 bp, separated by two inverted repeats of 27,009 bp. The G. mangostana plastome shows four minor structural modifications including infA gene loss, rpl32 gene loss, ycf3 gene intron loss and a 363 bp inversion between trnV-UAC and atpE gene. The plastome contains 111 genes, of which 77 are protein-coding genes, 30 are tRNA genes and four are rRNA genes. The average A-T content of the plastome is 63.9%. A total of 110 simple sequence loci are identified from the genome. Phylogenetic analysis reveals that G. mangostana is a sister group of Erythroxylum novogranatense (Erythroxylaceae) with 78% bootstrap support.


Using focused ethnography to inform biomedical research infrastructure enhancement at primarily undergraduate institutions.
The National Institutes of Health (NIH) supports 24 IDeA Networks of Biomedical Research Excellence (INBRE) Programs that help develop university-based biomedical research capacity in states that historically receive low levels of extramural grant support. To assess the effectiveness of the Arkansas INBRE in meeting its biomedical research capacity-building goals, we evaluated how the context (i.e., local and institutional settings) at two undergraduate institutions impacted variability in science faculty use of program resources. Data were collected by in-depth interviews with faculty and administrators (N = 9), focused observations, a review of Arkansas INBRE databases, and internet searches. Content analysis was used to code interview transcripts and field notes, and then qualitative data were integrated with data from databases and internet searches to construct two institutional case summaries. Constant comparison was used to identify similarities and differences between the institutions that helped to explain variability in how frequently faculty used Arkansas INBRE resources, including an enrollment crisis at undergraduate institutions in the United States and the presence or absence of a robust research culture at each institution. These findings were used to suggest program improvements (e.g., classroom-based research) that could further strengthen biomedical research capacity in Arkansas. As some barriers to program effectiveness are likely found in other IDeA-eligible states, improvements suggested for the Arkansas INBRE could apply to INBRE programs elsewhere.NEW & NOTEWORTHY This article describes results from an approach to program evaluation (i.e., focused ethnography) that has not been previously used to evaluate grant mechanisms. This "experience near" approach, which involved qualitative interviews and firsthand observations, lent valuable insights into how broader and institutional contexts at two primarily undergraduate institutions hindered or facilitated use of Arkansas INBRE resources. The insights gained can be used to enhance the Arkansas INBRE, which aims to strengthen the statewide biomedical infrastructure.


Taxol for the treatment of proliferative vitreoretinopathy.
Proliferative vitreoretinopathy (PVR) results in retinal detachment and visual impairment due to fibroblastic proliferation in the vitreous and subsequent cellular contraction. The authors have used an in vitro model for PVR to evaluate the action of the antineoplastic drug, taxol, on chorioretinal fibroblast proliferation and contractility. Dose response curves obtained show taxol to be a potent inhibitor of both cellular events. Fifty percent inhibition of contraction and proliferation occurred at 2 X 10(-8)M and 3 X 10(-9)M, respectively. On the basis of this pharmacodynamic data, three dosage regimes were chosen to evaluate possible prevention of PVR in an animal model based on the intravitreal injection of cultured fibroblasts. These animals trials show that a single intravitreal dose of either 35 micrograms or 0.5 microgram taxol significantly reduces incidence and extent of PVR. The average grade of vitreoretinal traction at 28 days for 35 micrograms taxol and 250,000 cells was 0.4 (control 1.8); for 35 micrograms taxol and 700,000 cells, 1.0 (control 2.2); and for 0.5 microgram taxol and 250,000 cells, 1.0 (control 2.3). Delayed optic nerve damage was noted with the highest dose used, but a good therapeutic margin may exist. Long-term clinical histopathologic and electrophysiologic studies will be required. The authors conclude from these preliminary studies that taxol holds definite promise for the relief of traction retinal detachment and PVR.


Correlation between Serum MMP-2/-16 Levels and Inflammation in Patients with Deep Vein Thrombosis.
The aim of the study was to clarify the correlation between serum MMP-2/-16 and inflammation in patients with deep venous thrombosis (DVT). Sixty DVT patients and 60 healthy people who underwent health examinations were collected. Serum MMP-2/-16, IL-6/-8, and TNF-α were determined by ELISA. MMP-2/-16 protein levels were detected by western blot, and IL-6/-8 and TNF-α by RT-qPCR. Correlation analysis was performed on MMP-2/-16xdd, IL-6/-8, and TNF-α in DVT patients. MMP-2/-16, IL-6/-8, and TNF-α in DVT patients after treatment were lower than before treatment. Serum IL-6/-8 and TNF-α levels in DVT patients were both positively correlated with MMP-2/-16 levels. MMP-2/-16 and inflammatory factors are related to DVT development, and IL-6/-8 and TNF-α are positively correlated with MMP-2/-16.


Hypoxia: Friend or Foe for drug delivery in Pancreatic Cancer.
Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal solid tumors with an overall five-year survival rate of that has only just reached 10%. The tumor microenvironment of PDAC is characterized by desmoplasia, which consist of dense stroma of fibroblasts and inflammatory cells, resulting in a hypoxic environment due to limited oxygen diffusion through the tumor. Hypoxia contributes to the aggressive tumor biology by promoting tumor progression, malignancy, and promoting resistance to conventional and targeted therapeutic agents. In depth research in the area has identified that hypoxia modulates the tumor biology through hypoxia inducible factors (HIFs), which not only are the key determinant of pancreatic malignancy but also an important target for therapy. In this review, we summarize the recent advances in understanding hypoxia driven phenotypes, which are responsible for the highly aggressive and metastatic characteristics of pancreatic cancer, and how hypoxia can be exploited as a target for drug delivery.


[Studies on the chemical constituents of Desmodium styracifolium (Osbeck) Merr].
A new alkaloid, named desmodimine, C12H15NO4, gum, and a new natural product, named desmodilactone, C8H13NO3, mp 84-85 degrees C have been isolated from the aerial parts of Desmodium styracifolium (Osbeck) Merr. belonging Leguminosae. On the basis of spectral analysis their structures were deduced as formula I and II. In addition, lupenone (III), lupeol (IV), tritriacontane (V), stearic acid (VI), eicosanoic acid eicosyl ester (VIII) and beta-sitosterol (VII) were isolated for the first time from this plant.


Increased risk of acute pancreatitis and biliary disease observed in patients with type 2 diabetes: a retrospective cohort study.
The objective of this study was to assess the risk of acute pancreatitis in patients with type 2 diabetes compared with that in patients without diabetes. We also examined the risk of biliary disease (defined as occurrence of cholelithiasis, acute cholecystitis, or cholecystectomy), which is a major cause of pancreatitis. We conducted a retrospective cohort study using a large, geographically diverse U.S. health care claims database. Eligible patients (>or=18 years) were enrolled for at least 12 continuous months (1999-2005), with no incident events of pancreatitis or biliary disease during that 1 year baseline period. ICD-9 codes and prescription data were used to identify patients with type 2 diabetes; ICD-9 codes were also used to identify cases of pancreatitis and biliary disease. Overall, 337,067 patients with type 2 diabetes were matched on age and sex with 337,067 patients without diabetes. Incidence rates of disease and 95% CI were calculated per 100,000 person-years of exposure. The type 2 diabetic cohort had a 2.83-fold (95% CI 2.61-3.06) greater risk of pancreatitis and 1.91-fold (1.84-1.99) greater risk of biliary disease compared with the nondiabetic cohort. Relative to patients of corresponding age without diabetes, younger type 2 diabetic patients had the highest risk of pancreatitis (<45 years: incidence rate ratio [IRR] 5.26 [95% CI 4.31-6.42]; >or=45 years: 2.44 [2.23-2.66]). These data suggest that patients with type 2 diabetes may have an increased risk of acute pancreatitis and biliary disease.


Short-term treatment with 6-DMAP and demecolcine improves developmental competence of electrically or Thi/DTT-activated porcine parthenogenetic embryos.
Treatment with 6-dimethylaminopurine (6-DMAP) or demecolcine (DE) for several (at least 2) hours after artificial activation is known to improve in vitro development of porcine embryos. However, several reports have also shown that treatments with these chemicals induce apoptosis. The aim of this study was to find out whether short-term treatment with 6-DMAP and DE combined with electrical or thimerosal/dithiothreitol (Thi/DTT) activation had a beneficial effect on development of parthenogenetically activated porcine oocytes. We additionally treated embryos with 6-DMAP (2 mM) and/or DE (0.4 microg/ml) for a short time (40 min) after an electrical pulse (EP) or Thi/DTT. As a result, short-term treatment with 6-DMAP and DE successfully induced development of electrically or Thi/DTT-activated porcine parthenogenetic embryos with no significant difference in cleavage rate, blastocyst formation rate and total cell number compared with long-term treatment. To find optimal activation protocol, cleavage rate, blastocyst formation rate and total cell number were compared between EP and Thi/DTT treatments. Thi/DTT + 6-DMAP + DE showed significantly higher blastocyst formation rate (36.1 ± 3.5%) and total cell number (46.9 ± 1.0) than other groups (EP + 6-DMAP + DE, EP + Thi/DTT + 6-DMAP + DE: 23.3 ± 3.0%, 42.2 ± 1.1 and 17.2 ± 2.7%, 36.7 ± 1.5, respectively). In conclusion, this study demonstrates that short-term treatment with 6-DMAP and DE is as effective as the standard long-term treatment and Thi/DTT + 6-DMAP + DE exerts a synergistic effect.


[Inhibition of tumor neo-angiogenesis and induction of apoptosis as properties of docetaxel (taxotere)].
Paclitaxel and docetaxel are potent drugs that are effective in the treatment of malignant tumors. The cytotoxic action of these drugs is not fully understood, but it appears to be mediated mainly through mitotic arrest and subsequent apoptosis. Because no information is available on the antiangiogenesis action of docetaxel, the investigations were performed to determine whether inhibition of neoangiogenesis plays a role in docetaxel's antitumor efficacy. Four different mouse tumors, two squamous cell carcinomas (SCC-IV; SCC-VII) and two adenocarcinomas (MCA-4; MCA-29) were assayed for angiogenic activity using the in vivo i.c. angiogenesis assay. Tumor cells (5 x 10(5)) were injected i.c. into the skin flap over the abdominal wall, and the number of new blood vessels at the tumor cell injection site was determined 2, 4, 6, 8, 10 and 12 days later. The mice were treated with docetaxel (Taxotere--31.3 mg/kg i.v.) 1 or 4 days after tumor cell injection. The number of new blood vessels increased with time. Docetaxel reduced the number of newly formed blood vessels in MCAs, but not in SCCs. The reduction was associated with slower tumor growth. In a separate set of experiments we observed that docetaxel's inhibitory effect on the two MCAs was histologically associated with massive tumor cell destruction by means of both apoptosis and necrosis. This was not observed for the two SCCs. Since no reduction in blood vessels occurred in tumors unresponsive to docetaxel, the inhibition of neoangiogenesis in docetaxel-responsive tumors was likely the result of a decrease in angiogenic stimuli due to docetaxel's destruction of tumor cells.


A simple training tool for CT-guided spinal pain management.
The use of models as training tools to learn and practice medical skills has become an important part of medical education. Image-guided spinal interventions for lower back pain are probably one of the most commonly performed procedures in interventional radiology. Thus, a training model for these types of interventions would be helpful. This article presents a simple training tool for computed tomography guided spinal pain interventions. The model is described, and the potential advantages in training are discussed.


Clonal emergence of Klebsiella pneumoniae ST14 co-producing OXA-48-type and NDM carbapenemases with high rate of colistin resistance in Dubai, United Arab Emirates.
Few studies have addressed the molecular epidemiology of carbapenem-resistant Enterobacteriaceae (CRE) isolates in the Arabian Peninsula, and such investigations have been missing from Dubai, a major economical, tourism and medical centre of the region. The antibiotic susceptibility, the carbapenemase type produced, and the clonality of 89 CRE strains isolated in five major Dubai hospitals in June 2015 to June 2016 were determined. Thirty-three percent of the collection of 70 Klebsiella pneumoniae, 13 Escherichia coli and 6 other Enterobacteriaceae were extremely drug resistant, 27% were resistant to colistin, and 4.5% (4 K. pneumoniae isolates) were resistant to all antibiotics tested. The colistin resistance rate in K. pneumoniae was 31.4%. None of the isolates carried mobile colistin resistance genes. Seventy-seven isolates produced carbapenemase: 53.3% OXA-48-like, 24.7% NDM and 22.1% both OXA-48-like and NDM, respectively. Pulsed-field gel electrophoresis clustered 50% of K. pneumoniae into a 35-membered group, which showed significant association with double carbapenemase production, with extreme drug resistance, and with being isolated from Emirati patients. Members of the cluster belonged to sequence type ST14. The rate of colistin resistance in K. pneumoniae ST14 was 37.1% vs. 27.1% of K. pneumoniae isolates outside of the cluster. Two of the panresistant K. pneumoniae isolates also belonged to ST14, whereas the other two were ST15 and ST231, respectively. In conclusion, beyond the overall high colistin resistance rate in CRE, the emergence of a highly resistant clone of K. pneumoniae ST14 in all Dubai hospitals investigated is a serious problem requiring immediate attention.


A new position utilizing the effect of gravity in proximal ureteral stones, ureteroscopic lithotripsy in the reverse Trendelenburg position: a prospective, randomized, comparative study.
To evaluate the effect of the reverse Trendelenburg position in patients undergoing ureteroscopic lithotripsy for proximal ureteral stones. The study included 167 patients who underwent ureteroscopic lithotripsy for proximal ureter stones between December 2020 and September 2022. The patients were randomly assigned to one of three groups: standard lithotomy (n:55), 10° reverse Trendelenburg (n:55), and 20° reverse Trendelenburg (n:57). Preoperative information, including age, sex, body mass index (BMI), previous shock wave lithotripsy (SWL), stone side, volume, and density, distance to the ureteropelvic junction (UPJ) of the stone, and hydronephrosis degree. Stone-free status was evaluated with computed tomography (CT) at 4 weeks postoperatively. The groups were compared in respect of stone migration, stone-free rate, use of flexible ureterorenoscope, operating time, postoperative length of stay in the hospital, and complications. No statistically significant difference was determined between the groups with respect to age, sex, BMI, previous SWL, stone side, volume and density, distance to the UPJ of the stone, and hydronephrosis degree (p > 0.05 for all). Statistically significant differences were determined between the groups with respect to stone migration (p = 0.001), stone-free rate (p < 0.001), use of flexible ureterorenoscope (p = 0.01), operating time (p < 0.001), hospital length of stay (p < 0.001), postoperative fever (p = 0.002), and total complications (p = 0.01). A new patient position is presented in this study, which can be used in ureteroscopic lithotripsy performed for proximal ureteral stones. The reverse Trendelenburg position constitutes a surgical method that can be used safely and successfully in the treatment of proximal ureteral stones. NCT04894058, 05/21/2021, Prospectively registered.


[Value of antioxidants and vitamins in cardiovascular prevention and therapy].
Experimental as well as epidemiological data suggest the use of antioxidants for therapy of atherosclerosis. Feasible, however, seems only the use of antioxidant vitamins. Recent knowledge from published data seems to justify the use of low-dose supplementation in primary prevention of vascular disease. High-dose intervention in secondary prevention, despite promising results from intervention studies, needs further controlled studies, addressing optimal dose or combination therapies.


A nonlinear model for transient responses from light-adapted wolf spider eyes.
A quantitative model is proposed to test the hypothesis that the dynamics of nonlinearities in retinal action potentials from light-adapted wolf spider eyes may be due to delayed asymmetries in responses of the visual cells. For purposes of calculation, these delayed asymmetries are generated in an analogue by a time-variant resistance. It is first shown that for small incremental stimuli, the linear behavior of such a resistance describes peaking and low frequency phase lead in frequency responses of the eye to sinusoidal modulations of background illumination. It also describes the overshoots in linear step responses. It is next shown that the analogue accounts for nonlinear transient and short term DC responses to large positive and negative step stimuli and for the variations in these responses with changes in degree of light adaptation. Finally, a physiological model is proposed in which the delayed asymmetries in response are attributed to delayed rectification by the visual cell membrane. In this model, cascaded chemical reactions may serve to transduce visual stimuli into membrane resistance changes.


Suicidal Ideation among Youths at Risk of School Dropout: Impact of Student Demographics, Stressors, and Academic Self-Concept.
In the United States, suicidal ideation is an issue for high school-age youths. Research supports that youths who have learning difficulties and who are at risk of high school dropout are at greater risk for suicidal ideation. Although alternative high schools address both student academics and emotional health, they are underused, nonclinical settings for understanding and addressing suicidal ideation. This study aimed to examine the impact of student identity, external stressors, and academic self-concept on suicidal ideation among sexual and ethnic minority and underserved students enrolled in an alternative education public high school. The student sample (N = 103) completed a onetime survey comprised of the Suicidal Ideation Questionnaire-Junior, the Cultural Assessment of Risk of Suicide, the Coddington Life Events Scale for Adolescents, and the Piers Harris 2. Results of hierarchical linear regression indicated that identifying as nonheterosexual and experiencing discrimination were associated with greater student reporting of suicidal ideation. Identifying as Latino and other non-White was associated with lower reporting of suicidal ideation. Controlling for student demographics and external stressors, positive academic self-concept was associated with a lower reporting of suicidal ideation. Findings have future implications for health social work, suicide prevention and intervention, and education policy.


Using Facial Animation to Increase the Enfacement Illusion and Avatar Self-Identification.
Through avatar embodiment in Virtual Reality (VR) we can achieve the illusion that an avatar is substituting our body: the avatar moves as we move and we see it from a first person perspective. However, self-identification, the process of identifying a representation as being oneself, poses new challenges because a key determinant is that we see and have agency in our own face. Providing control over the face is hard with current HMD technologies because face tracking is either cumbersome or error prone. However, limited animation is easily achieved based on speaking. We investigate the level of avatar enfacement, that is believing that a picture of a face is one's own face, with three levels of facial animation: (i) one in which the facial expressions of the avatars are static, (ii) one in which we implement lip-sync motion and (iii) one in which the avatar presents lip-sync plus additional facial animations, with blinks, designed by a professional animator. We measure self-identification using a face morphing tool that morphs from the face of the participant to the face of a gender matched avatar. We find that self-identification on avatars can be increased through pre-baked animations even when these are not photorealistic nor look like the participant.


Plasmonic waveguides with low polarization dependence.
Plasmonic waveguides essentially support only transverse magnetic modes. A novel plasmonic waveguide consisting of hybrid plasmonic waveguides in both vertical and horizontal directions is proposed to reduce the polarization dependence. In a combined waveguide, surface plasmon polariton (SPP) modes polarized in both vertical and horizontal directions exist in the correspondingly oriented hybrid plasmonic waveguide. In an optimized structure, anticrossing mode coupling is observed between these two SPP modes with a low birefringence by finite-difference time-domain simulation. The energy flux clearly shows the polarization-selective coupling between the polarized guided modes in the feeding silicon waveguide and those in the combined waveguide. Coupling efficiency above 65% is obtained for both polarizations. The proposed plasmonic combined waveguide has a potential application in guiding and processing of light from a fiber with a random polarization state.


Femoral vein valve incompetence as a risk factor for junctional recurrence.
Background Recurrent varicose veins occur up to 80% of procedures. The sapheno-femoral junction can be involved in more than 50% of cases. A detailed pathophysiological explanation of the phenomenon is still missing. The aim of the present work is to evaluate the role of femoral vein incompetence as risk factor for sapheno-femoral junction recurrence. Methods Three-hundred-eighty-one patients presenting an incompetent great saphenous vein system and eventually also an incompetent femoral tract (C2-6EpAsdPr) underwent a great saphenous vein high ligation with flush ligation also of the incompetent tributaries along the leg, sparing the saphenous trunk. Pre-operatively, all patients underwent a sonographic evaluation assessing the superficial and deep venous systems, including a detailed analysis of the iliac-femoral vein tract above the sapheno-femoral junction. A retrospective statistical analysis assessed the recurrence risk associated with iliac-femoral vein tract incompetence. Results In a 5.5 ± 1.9 years follow-up, great saphenous vein trunk reflux recurrence was detected in 45/381 (11.8%) cases. The reflux source was found in a reconnected sapheno-femoral stump in 11/45 cases (24.5%), in the pelvic network in 8/45 cases (17.8%), in a neovascularization process in 7/45 (15.5%) and in a newly incompetent great saphenous vein tributary in 19/45 (42.2%). At the pre-operative assessment, iliac-femoral vein tract reflux was present in 7 (26.9%) of the 26 cases who developed a sapheno-femoral junction recurrence and in 25 (7%) of the 355 patients who did not demonstrate sapheno-femoral junction recurrence (odds ratio: 4.8; confidence interval 95%: 1.8-12.6; p < .003). Discussion Despite many technical diagnostic and therapeutic refinements, varicose veins recurrence remains a frequent event. The present investigation points out the association among iliac-femoral vein tract incompetence and sapheno-femoral junction recurrences after high ligation.


Rehabilitation in neuropsychiatry.
Patients with neuropsychiatric disorders may present with multiple functional deficits. A rehabilitation approach tends to focus on problems presented and involve multidisciplinary assessment and therapeutic programmes. Ideally the programme should be flexible and tailored to the needs of the individual and his or her family.


The new histopathologic classification of ANCA-associated GN and its association with renal outcomes in childhood.
A proposed histopathologic classification for ANCA-associated GN is predictive of long-term renal outcome in adult populations. This study sought to validate this system in a pediatric cohort. This was a retrospective, single-center, cohort study of 40 children diagnosed and followed until their transition to adult care at one institution between 1987 and 2012. Renal biopsy specimens were reviewed by a pathologist blinded to patient outcome and were classified using the new histopathologic classification system of focal, crescentic, mixed, and sclerotic groups. Time to the composite outcome of CKD stages 3 and 4 (determined by eGFR with repeated creatinine measures using the Schwartz equation) or ESRD (defined as dialysis dependence or transplantation) were ascertained. The study population consisted of 40 children (70% female), followed for a median of 2.4 years. The biopsy specimens were categorized as focal in 13 patients (32.5%), crescentic in 20 (50%), mixed in two (5%), and sclerotic in five (12.5%). Mixed and crescentic were combined for analyses. Survival analysis of time to the composite renal endpoint of at least 3 months of eGFR<60 ml/min per 1.73 m(2) or ESRD differed significantly among the three biopsy groups log-rank P<0.001), with an adjusted hazard ratio of 3.14 (95% confidence interval, 0.68 to 14.4) in the crescentic/mixed group and 23.6 (95% confidence interval, 3.9 to 144.2) in the sclerotic category compared with the focal category. The probability of having an eGFR>60 ml/min per 1.73 m(2) at 2 years was 100% for the focal, 56.5% for the crescentic/mixed, and 0% for the sclerotic biopsy categories. This study showed the clinical utility of this histopathologic classification system and its ability to discriminate renal outcomes among children with ANCA GN.


Pathologic calcium phosphate deposition in model systems.
Pathologic calcium phosphate deposition occurs mainly in tissues exposed to highly supersaturated body fluids such as urine and saliva. In vitro models employed to study pathologic calcification include aqueous solutions and hydrogels. Results from studies on de novo formation of various biologic calcium phosphates in aqueous solutions resembling various body fluids have been rewarding. Among others, the de novo results have shown that the formation conditions for each calcium phosphate crystal phase are quite different and are pH dependent, and yet all phases including brushite can form in neutral solutions. This is an important finding because when coupled to the facts that all calcium phosphates including brushite are more soluble in acidic solutions than in neutral ones and that, except in extreme cases of hypercalciuria and/or hyperphosphaturia, body fluid Ca and Pi are not very high, it suggests that in most cases pathologic calcification occurs in alkaline or near neutral milieus. HAP is ubiquitous because it is the most insoluble calcium phosphate crystal phase in alkaline or slightly acidic fluids. In fluids close to neutrality, whitlockite is the next favored, provided that the fluid Mg:Ca ration is neither too low nor too high. Although OCP is only slightly more soluble than whitlockite in near neutral milieus, it is favored only by low fluid Ca:Pi and Mg:Ca ratios and transforms easily to HAP. Except in very acidic milieus, brushite is the most soluble biologic calcium phosphate. Its formation is favored by acidic body fluids with high Ca x Pi or by neutral or slightly alkaline ones with very low Ca:Pi ratio or high Mg:Ca ratio.


Production and consumption of hydrogen in hot spring microbial mats dominated by a filamentous anoxygenic photosynthetic bacterium.
Microbial mats containing the filamentous anoxygenic photosynthetic bacterium Chloroflexus aggregans develop at Nakabusa hot spring in Japan. Under anaerobic conditions in these mats, interspecies interaction between sulfate-reducing bacteria as sulfide producers and C. aggregans as a sulfide consumer has been proposed to constitute a sulfur cycle; however, the electron donor utilized for microbial sulfide production at Nakabusa remains to be identified. In order to determine this electron donor and its source, ex situ experimental incubation of mats was explored. In the presence of molybdate, which inhibits biological sulfate reduction, hydrogen gas was released from mat samples, indicating that this hydrogen is normally consumed as an electron donor by sulfate-reducing bacteria. Hydrogen production decreased under illumination, indicating that C. aggregans also functions as a hydrogen consumer. Small amounts of hydrogen may have also been consumed for sulfur reduction. Clone library analysis of 16S rRNA genes amplified from the mats indicated the existence of several species of hydrogen-producing fermentative bacteria. Among them, the most dominant fermenter, Fervidobacterium sp., was successfully isolated. This isolate produced hydrogen through the fermentation of organic carbon. Dispersion of microbial cells in the mats resulted in hydrogen production without the addition of molybdate, suggesting that simultaneous production and consumption of hydrogen in the mats requires dense packing of cells. We propose a cyclic electron flow within the microbial mats, i.e., electron flow occurs through three elements: S (elemental sulfur, sulfide, sulfate), C (carbon dioxide, organic carbon) and H (di-hydrogen, protons).


The Effects of Using Pancreases Obtained from Brain-Dead Donors for Clinical Islet Transplantation in Japan.
The pool of brain-dead donors (BDDs) was increased with the revision to the relevant law in 2010, and islet transplantation from BDDs was started in 2013. The present study assessed the influence of using pancreases from BDDs on islet transplantation in Japan. The donor information registered with the secretariat of islet transplants from 2012 was reviewed, and the results of 86 clinical islet isolations performed in Japan between 2003 and 2018 with non-heart-beating donors (NHBDs) (n = 71) and BDDs (n = 15) were investigated. The number of cases for which donor information was registered with the secretariat of islet transplants increased to 1.84 cases/month from 2013 to 2018 in comparison to 1.44/month in 2012, when only NHBDs were used. The median pancreatic islet yield was 275,550 IEQ (Islet equivalents) in the NHBD group but 3,627,000 in the BDD group, which amounted to a statistically significant difference (p = 0.02). As a result, 38/71 cases (53.5%) were achieved successful islet isolation (>5000 IEQ per recipient weight (kg)) was achieved in 38/71 cases (53.5%) in the NHBD group, and 12/15 cases (80.0%) in the BDD group; thus, the rate of successful islet transplantation was higher in the BDD group. The use of pancreases from BDDs has increased the overall number of cases for which donor information is registered with the secretariat of islet transplants and has improved the performance of islet isolation, thereby increasing the probability of successfully achieving islet transplantation.


Effect of Resin Cement at Different Thicknesses on the Fatigue Shear Bond Strength to Leucite Ceramic.
This in vitro study was performed to evaluate fatigue survival by shear test in the union of leucite-reinforced feldspathic ceramic using different cement thicknesses. Leucite-reinforced glass ceramics blocks were sectioned in 2-mm thick slices where resin cylinders were cemented. The samples were distributed in two experimental groups (n = 20) according to the cement thickness (60 and 300 μm). The specimens of each group were submitted to the stepwise fatigue test in the mechanical cycling machine under shear stress state, with a frequency of 2 Hz, a step-size of 0.16 bar, starting with a load of 31 N (1.0 bar) and a lifetime of 20,000 cycles at each load step. The samples were analyzed in a stereomicroscope and scanning electron microscopy to determine the failure type. There is no significant difference between the mean values of shear bond strength according to both groups. Log-rank (p = 0.925) and Wilcoxon (p = 0.520) tests revealed a similar survival probability in both cement layer thicknesses according to the confidence interval (95%). The fracture analysis showed that the mixed failure was the most common failure type in the 300-μm thickness group (80%), while adhesive failure was predominant in the 60-μm thickness group (67%). The different cement thicknesses did not influence the leucite ceramic bonding in fatigue shear testing; however, the thicker cement layer increased the predominance of the ceramic material failure. The resin cement thicknesses bonded to leucite ceramic did not influence the long-term interfacial shear bond strength, although thicker cement layer increased the ceramic material cohesive failure. Regardless the cement layer thickness, the shear bond strength lifetime decreases under fatigue.


Bayesian predictor combination for lossless image compression.
Adaptive predictor combination (APC) is a framework for combining multiple predictors for lossless image compression and is often at the core of state-of-the-art algorithms. In this paper, a Bayesian parameter estimation scheme is proposed for APC. Extensive experiments using natural, medical, and remote sensing images of 8–16 bit/pixel have confirmed that the predictive performance is consistently better than that of APC for any combination of fixed predictors and with only a marginal increase in computational complexity. The predictive performance improves with every additional fixed predictor, a property that is not found in other predictor combination schemes studied in this paper. Analysis and simulation show that the performance of the proposed algorithm is not sensitive to the choice of hyper-parameters of the prior distributions. Furthermore, the proposed prediction scheme provides a theoretical justification for the error correction stage that is often included as part of a prediction process.


Benzodiazepine receptor increases after repeated seizures: evidence for localization to dentate granule cells.
Repeated seizures, whether induced by kindling or electroshock, result in increased numbers of benzodiazepine receptors in hippocampal formation membranes. We sought to determine the cellular constituents containing the receptor increases. Binding studies of microdissected samples localized the receptor increases to fascia dentata. [3H]Flunitrazepam autoradiographic studies showed increases of silver grain density over the granule cell and molecular layers of fascia dentata but not in other regions of hippocampal formation. Destruction of granule cells by colchicine or neonatal x-irradiation was associated with marked decrease of benzodiazepine receptor binding. Together, these results provide evidence for localization of the receptor increases to the somata and dendritic tree of the granule cells. We suggest that this cellular localization may provide a clue to the network of altered neural circuitry underlying amygdala kindling.


An Anatomically Constrained Model for Path Integration in the Bee Brain.
Path integration is a widespread navigational strategy in which directional changes and distance covered are continuously integrated on an outward journey, enabling a straight-line return to home. Bees use vision for this task-a celestial-cue-based visual compass and an optic-flow-based visual odometer-but the underlying neural integration mechanisms are unknown. Using intracellular electrophysiology, we show that polarized-light-based compass neurons and optic-flow-based speed-encoding neurons converge in the central complex of the bee brain, and through block-face electron microscopy, we identify potential integrator cells. Based on plausible output targets for these cells, we propose a complete circuit for path integration and steering in the central complex, with anatomically identified neurons suggested for each processing step. The resulting model circuit is thus fully constrained biologically and provides a functional interpretation for many previously unexplained architectural features of the central complex. Moreover, we show that the receptive fields of the newly discovered speed neurons can support path integration for the holonomic motion (i.e., a ground velocity that is not precisely aligned with body orientation) typical of bee flight, a feature not captured in any previously proposed model of path integration. In a broader context, the model circuit presented provides a general mechanism for producing steering signals by comparing current and desired headings-suggesting a more basic function for central complex connectivity, from which path integration may have evolved.


Diverse mechanisms in the generation of human beta-tubulin pseudogenes.
The sequence of two human beta-tubulin pseudogenes is described. One contains an intervening sequence but lacks sequences encoding the 55 N-terminal amino acids of the polypeptide chain. A second has no introns but has a polyadenylate signal and an oligoadenylate tract at its 3' end, and it is flanked by a short direct repeat. These sequences have arisen by different mechanisms, including one that probably involves reverse transcription of a processed messenger RNA and reintegration of the complementary DNA copy into the genome.


[Problem of cutaneous tuberculosis].
Case histories of 97 patients were analysed to study the diagnosis, differential diagnosis and incidence of recurrences of tuberculosis of the skin. A combined examination revealed Basin erythema in 57.7% of the patients, lupus vulgaris in 29.9% and papulonecrotic tuberculosis of the skin in 12.4%. Recurrences were recorded in 15.4% of the cases. Our study gives evidence that tuberculosis of the skin is diagnosed from the combined examination of the patient in which histologic study of a skin biopsy specimen is most essential. The differential diagnosis of tuberculosis of the skin makes difficult the distinction between the disseminated forms and allergic vasculitis and sarcoidosis of the skin. The relapse depends on how adequate the major and antirecurrence courses of antibacterial therapy were.


Adolescent personality moderates genetic and environmental influences on relationships with parents.
In contrast with early theories of socialization that emphasized the role of parents in shaping their children's personalities, recent empirical evidence suggests an evocative relationship between adolescent personality traits and the quality of the parent-adolescent relationship. Research using behavior genetic methods suggests that the association between personality and parenting is genetically mediated, such that the genetic effects on adolescent personality traits overlap with the genetic effects on parenting behavior. In the current study, the authors examined whether the etiology of this relationship might change depending on the adolescent's personality. Biometrical moderation models were used to test for gene- environment interaction and correlation between personality traits and measures of conflict, regard, and involvement with parents in a sample of 2,452 adolescents (M age = 17.79 years). They found significant moderation of both positive and negative qualities of the parent-adolescent relationship, such that the genetic and environmental variance in relationship quality varied as functions of the adolescent's levels of personality. These findings support the importance of adolescent personality in the development of the quality of the parent-adolescent relationship.


Role of lung perfusion scintigraphy in relation to chest computed tomography and pulmonary function in the evaluation of candidates for lung volume reduction surgery.
Lung perfusion scintigraphy is employed to evaluate patients with severe emphysema who are candidates for lung volume reduction surgery (LVRS). Our purpose was to investigate the role of scintigraphy in relation to chest computed tomography (CT) and lung function in this setting. Six observers blinded to clinical data retrospectively scored preoperative scintigrams of 70 patients undergoing bilateral video-assisted LVRS according to the distribution of lung perfusion as homogeneous, intermediately heterogeneous, or markedly heterogeneous. Heterogeneity of emphysema distribution was also assessed by chest CT. Dyspnea and pulmonary function were measured preoperatively and 3 mo postoperatively. In 42 patients with markedly heterogeneous, in 18 with intermediately heterogeneous, and in 10 with homogeneous perfusion, mean (+/- SE) FEV1 increased by 57 +/- 8% (p < 0.0001), 38 +/- 9% (p < 0.001), and 23 +/- 9% (p = NS) (p = NS for intergroup comparisons). In a multiple regression analysis, functional improvement after LVRS was more closely correlated with preoperative hyperinflation and the degree of emphysema heterogeneity estimated by chest CT than with the degree of perfusion heterogeneity assessed by scintigraphy. In 16 of 22 patients with homogeneous emphysema distribution in the chest CT scintigraphy revealed intermediately or markedly heterogeneous perfusion. We conclude that lung perfusion scintigraphy has a limited role in prediction of outcome, but it may help to identify target areas for resection in LVRS candidates with homogeneous CT morphology.


Family-centred services in The Netherlands: validating a self-report measure for paediatric service providers.
To validate the Dutch translation of the Canadian Measure of Processes of Care for Service Providers questionnaire (MPOC-SP) for use in paediatric rehabilitation settings in the Netherlands. The construct validity, content validity, face validity, and reliability of the Dutch MPOC-SP were determined. The 163 service providers that participated in the validation study represented seven children's rehabilitation centres and affiliated schools in the Netherlands (overall response rate 55.6%). In this sample 19 disciplines were represented. The MPOC-SP consists of 27 items (assessing four domains) and was designed to examine how service providers think about the quality of care they provide and to assess the extent to which these services are family centred. Fifty-three service providers filled out an additional face validity questionnaire. All items correlated best and significantly with their own scale score (r(s) 0.48-0.82, P<0.001). The Pearson's correlation coefficients were all significant and confirmed that the four scales measure different aspects of a same construct, namely family-centred service. The content validity and the face validity of the Dutch MPOC-SP were good, indicating the questionnaire measures relevant aspects of family-centred service delivery in paediatric rehabilitation settings in the Netherlands. The test-retest analyses (intraclass correlation coefficient (ICC) 0.83-0.89) and the internal consistency analyses (alpha 0.65-0.84) showed that the Dutch MPOC-SP is a reliable tool. The Dutch MPOC-SP is a reliable and valid instrument to measure the family-centredness of service delivery.


Comparison between Intravenous Sodium Valproate and Subcutaneous Sumatriptan for Treatment of Acute Migraine Attacks; Double-Blind Randomized Clinical Trial.
Sodium valproate (SV) has been approved for migraine prophylaxis and its intravenous form is used to treat acute migraine attacks. We compared the efficacy and safety of intravenous SV and subcutaneous Sumatriptan in managing acute migraine attacks. This double-blind randomized clinical trial divided 90 patients into two groups: one group received 400 mg of intravenous SV and the second group received 6 mg of subcutaneous Sumatriptan. Headache severity before treatment and half an hour, one hour, and two hours after treatment was measured based on the VNRS in the groups. Associated symptoms, i.e., photophobia, phonophobia, nausea, and vomiting, were assayed on admission and 2 hours after treatment. Side effects of the drugs were checked 2 hours after injection. Obtained data from the groups were compared. In both groups, pain decrement at the mentioned time points was significant (P<0.001), but had no significant difference (P>0.05), indicating the similar effect of both drugs on pain improvement. In the SV group, photophobia, phonophobia, nausea, and vomiting were improved significantly, while in the Sumatriptan group, only photophobia and vomiting were decreased significantly, indicating the advantage of SV in improving the associated symptoms. Nausea, vomiting, facial paresthesia, and hypotension were more significantly frequent in the Sumatriptan group than in the SV group (P<0.05). Intravenous SV (400 mg) was as effective as subcutaneous Sumatriptan in the treatment of acute migraine attacks, but with more improvement in associated symptoms and with fewer side effects. IRCT201108025943N4.


A deletion polymorphism of alpha(2)-macroglobulin gene and cerebral amyloid angiopathy.
alpha(2)-Macroglobulin may be implicated in amyloid beta protein deposition. A deletion in the exon 18 splice acceptor of the alpha(2)-macroglobulin gene (A2M) has been reported to be associated with risk for Alzheimer's disease (AD). In search of genetic risk factors for cerebral amyloid angiopathy (CAA), we investigated association of the A2M deletion polymorphism with CAA. The association between the severity of CAA and A2M deletion polymorphism was investigated in 178 autopsy cases of the elderly including 68 patients with AD. There was no significant difference in the severity of CAA between individuals with the A2M deletion allele and those without in the AD, non-AD, or total cases. Status for the epsilon4 allele of the apolipoprotein E gene did not influence the results. Our results suggest that the A2M deletion polymorphism may not be a definitive risk factor of CAA in the elderly, although further study with larger samples is necessary to confirm this.


Lung cancer in women, a different disease: survival differences by sex in Turkey.
In this study, we aimed to evaluate the effects of sex-based non-small cell lung cancer (NSCLC) varieties on survival rates. A retrospective study was performed in patients with NSCLC who were diagnosed by histological methods between the years 2000 and 2010. A chi-square test was used to compare variables. Overall survival (OS) was estimated by the Kaplan-Meier method. Of the 844 patients, 117 (13.9%) were women and 727 (86.1%) were men. Adenocarcinoma was more common in women than in men (p<0.0001). There were more women non-smokers than men (p<0.0001). There was no statistically significant difference in ECOG PS, weight loss>10%, stage, LDH, albumin and treatment between women and men. Women younger than 65 years (17.0 vs 12.0 months; p=0.03), who had adenocarcinoma histology (15.0 vs 10.0 months; p=0.006) and who had a hemoglobin level≥12 g/dL (18.0 vs 12.0 months; p=0.01) were found to have a better median OS rate than men. Median OS rates were found to be 13.0 months in females and 12.0 months in males (p=0.14). Among metastatic patients, the median OS was 11.0 months in females and 8.0 months in males (p=0.005). Among stage IIIB and stage IV patients who had first line platinum-based chemotherapy, the median OS was 17.0 months in women and 11.0 months in men (p=0.002). The response rate of chemotherapy was higher in women than in men (p=0.03). In our study, we found that survival duration is longer and chemotherapy response is better in women with NSCLC who do not have anemia or comorbidities and who are mostly non-smokers with adenocarcinomas. Further studies regarding the causes of these differences may provide clarity on this subject.


Nickel-catalyzed C-H/N-H annulation of aromatic amides with alkynes in the absence of a specific chelation system.
The Ni-catalyzed reaction of aromatic amides with alkynes in the presence of KOBu t involves C-H/N-H oxidative annulation to give 1(2H)-isoquinolinones. A key to the success of the reaction is the use of a catalytic amount of strong base, such as KOBu t . The reaction shows a high functional group compatibility. The reaction with unsymmetrical alkynes, such as 1-arylalkynes, gives the corresponding 1(2H)-isoquinolinones with a high level of regioselectivity. This discovery would lead to the development of Ni-catalyzed chelation-assisted C-H functionalization reactions without the need for a specific chelation system.


Human dendritic cells discriminate between viable and killed Toxoplasma gondii tachyzoites: dendritic cell activation after infection with viable parasites results in CD28 and CD40 ligand signaling that controls IL-12-dependent and -independent T cell production of IFN-gamma.
We studied how the interaction between human dendritic cells (DC) and Toxoplasma gondii influences the generation of cell-mediated immunity against the parasite. We demonstrate that viable, but not killed, tachyzoites of T. gondii altered the phenotype of immature DC. DC infected with viable parasites up-regulated the expression of CD40, CD80, CD86, and HLA-DR and down-regulated expression of CD115. These changes are indicative of DC activation induced by T. gondii. Viable and killed tachyzoites had contrasting effects on cytokine production. DC infected with viable T. gondii rather than DC that phagocytosed killed parasites induced secretion of high amounts of IFN-gamma by T cells from T. gondii-seronegative donors. IFN-gamma production in response to DC infected with viable parasites required CD28 and CD40 ligand (CD40L) signaling. In addition, this IFN-gamma response was dependent in part on IL-12 secretion. Production of IL-12 p70 occurred after interaction between T cells and DC infected with viable T. gondii, but not after incubation of T cells with DC plus killed tachyzoites. IL-12 synthesis was inhibited by blockade of CD40L signaling. IL-12-independent IFN-gamma production required CD80/CD86-CD28 interaction and, to a lesser extent, CD40-CD40L signaling. Taken together, T. gondii-induced activation of human DC is associated with T cell production of IFN-gamma through CD40-CD40L-dependent release of IL-12 and through CD80/CD86-CD28 and CD40-CD40L signaling that mediate IFN-gamma secretion even in the absence of bioactive IL-12.


Dexamethasone acutely suppresses the anabolic SNAT2/SLC38A2 amino acid transporter protein in L6-G8C5 rat skeletal muscle cells.
Chronic metabolic acidosis plays a role in cachexia by enhancing total proteolysis in skeletal muscle. Glucocorticoid also triggers proteolysis and plays a permissive role in the effect of acidosis. The System A amino acid transporter SNAT2/SLC38A2 is ubiquitously expressed in mammalian cells including muscle, performing Na+-dependent active import of neutral amino acids, and is strongly inhibited by low pH. Exposure of rat skeletal muscle cell line L6-G8C5 to low pH rapidly inhibits SNAT2 transport activity and enhances total proteolysis rate. Pharmacological inhibition or silencing of SNAT2 also enhances proteolysis. This study tests the hypothesis that the glucocorticoid dexamethasone (DEX), like low pH, inhibits SNAT2 activity in L6-G8C5 myotubes, thus contributing to total proteolysis. Incubation with 500 nM DEX for 4 h reduced the System A amino acid transport rate to half the rate in control cultures. This inhibition depended on glucocorticoid receptor-mediated gene transcription, but SNAT2 mRNA levels were unaffected by DEX. In contrast, the SNAT2 protein assessed by immunoblotting was significantly depleted. The co-inhibitory effects of DEX and low pH on System A transport activity were additive in stimulating total proteolysis. In keeping with this mechanism, DEX's inhibitory effect on SNAT2 transport activity was significantly blunted by the proteasome inhibitor MG132. Proof of principle was achieved in similar experiments using recombinant expression of a GFP-tagged SNAT2 fusion protein in HEK293A cells. It is concluded that DEX acutely depletes the SNAT2 transporter protein, at least partly through proteasome-dependent degradation of this functionally important transporter.


The administration of triiodothyronine to rats results in a lowering of the mitochondrial membrane potential in isolated hepatocytes.
Although thyroid status has been shown to influence the magnitude of the membrane potential in isolated rat-liver mitochondria, there is variation in the reported size and direction of the thyroid hormone-induced change relative to the normal state. Measurement of the mitochondrial membrane potential in intact hepatocytes isolated from hyperthyroid and euthyroid rats reveals that hyperthyroidism results in a decrease of approximately 30 mV in the magnitude of this potential relative to that in the euthyroid state. As well, the magnitude of the plasma membrane potential of hepatocytes from hyperthyroid rats is reduced by 6 mV compared with that in cells from euthyroid rats. The thyroid hormone-induced decrease in these potentials may reflect reported changes in the lipid composition of the membranes.


Anti-hyperlipidemic effect of methanol bark extract of Terminalia chebula in male albino Wistar rats.
Hyperlipidemia is known to be a major risk factor for the development of cardiovascular diseases (CVDs) which include atherosclerosis, coronary heart disease, and stroke. Although there are a large number of anti-hyperlipidemic drugs available, unfortunately, they all have side effects. Terminalia chebula Retz. (Combretaceae) is a plant used to treat cardiac disorders in the traditional Ayurveda medicine in India. The objective of this study was to assess the anti-hyperlipidemic properties of a methanol (MeOH) bark extract of T. chebula. Acute toxicity studies were performed according to the Organisation for Economic Cooperation and Development (OECD) guideline no. 423 using various doses (5, 50, 300, and 2000 mg/kg) of T. chebula bark. Anti-hyperlipidemic effect of MeOH bark extract of T. chebula at doses of 200, 400, and 600 mg/kg and fasting glucose levels after treatment with MeOH bark extract of T. chebula at doses of 200, 400, and 600 mg/kg were analyzed using commercially available kits. Acute toxicity studies did not show any morbidity and mortality at various doses. The MeOH extract of T. chebula bark at doses of 200, 400, and 600 mg/kg significantly lowered serum cholesterol and triglyceride levels. Moreover, the extract of T. chebula and the positive control atorvastatin-treated groups of animals showed a significant increase in the serum high-density lipoprotein (HDL) cholesterol levels in diet-induced hypercholesterolemic animals. The overall results confirm that the bark extract of T. chebula possesses significant anti-hyperlipidemic activity.


Microbiome and Metabolome Profiles Associated With Different Types of Short Bowel Syndrome: Implications for Treatment.
The gut microbiome and metabolome may significantly influence clinical outcomes in patients with short bowel syndrome (SBS). The study aimed to describe specific metagenomic/metabolomics profiles of different SBS types and to identify possible therapeutic targets. Fecal microbiome (FM), volatile organic compounds (VOCs), and bile acid (BA) spectrum were analyzed in parenteral nutrition (PN)-dependent SBS I, SBS II, and PN-independent (non-PN) SBS patients. FM in SBS I, SBS II, and non-PN SBS shared characteristic features (depletion of beneficial anaerobes, high abundance of Lactobacilaceae and Enterobacteriaceae). SBS I patients were characterized by the abundance of oxygen-tolerant microrganisms and depletion of strict anaerobes. Non-PN SBS subjects showed markers of partial FM normalization. FM dysbiosis was translated into VOC and BA profiles characteristic for each SBS cohort. A typical signature of all SBS patients comprised high saturated aldehydes and medium-chain fatty acids and reduced short-chain fatty acid (SCFA) content. Particularly, SBS I and II exhibited low protein metabolism intermediate (indole, p-cresol) content despite the hypothetical presence of relevant metabolism pathways. Distinctive non-PN SBS marker was high phenol content. SBS patients' BA fecal spectrum was enriched by chenodeoxycholic and deoxycholic acids and depleted of lithocholic acid. Environmental conditions in SBS gut significantly affect FM composition and metabolic activity. The common feature of diverse SBS subjects is the altered VOC/BA profile and the lack of important products of microbial metabolism. Strategies oriented on the microbiome/metabolome reconstitution and targeted delivery of key compounds may represent a promising therapeutic strategy in SBS patients.


Effects of molecular architecture of phospholipid polymers on surface modification of segmented polyurethanes.
To modify the surface properties of segmented polyurethane (SPU), effects of the molecular architecture of the 2-methacryloyloxyethyl phosphorylcholine (MPC) polymers on the performance of the SPU/MPC polymer membrane were investigated. We combined the random-type, block-type, and graft-type of the MPC polymers with a typical SPU, Tecoflex(®) using double solution casting procedure. The graft-type MPC polymers composed of a poly(MPC) main chain and poly(2-ethylhexyl methacrylate (EHMA)) side chains were synthesized through the combination of two different living radical polymerization techniques to regulate the density and chain length of the side chains. The SPU membranes modified with the MPC polymers were characterized using X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy. The results revealed that the MPC units were located on the SPU surface. Although the breaking strength of the SPU membranes modified with block-type poly(MPC-block-EHMA) and graft-type poly(MPC-graft-EHMA) was lower than that of SPU membranes modified with random-type poly(MPC-random-EHMA), their breaking strengths were adequate for manufacturing medical devices. On the other hand, better stability was observed in the MPC polymer layer on the SPU membrane after immersion in an aqueous medium, wherein the SPU membrane had been modified with the poly(MPC-graft-EHMA). This was because of the intermixing of the hydrophobic poly(EHMA) segments in the domain of the hard segments in the SPU membrane. After this modification, each SPU/MPC polymer membrane showed hydrophilic nature based on the MPC polymers and a dramatic suppression of protein adsorption. From these results, we concluded that the SPU membrane modified with the poly(MPC-graft-EHMA) was one of the promising polymeric biomaterials for making blood-contacting medical devices.


No mortality or pancreatic fistula after full-thickness suture pancreaticogastrostomy in 39 patients who underwent pancreaticoduodenectomy.
Pancreaticoduodenectomy is considered the standard operation for periampullary tumors. Despite major advances in pancreatic surgery, pancreatic fistula is still an important cause of morbidity and mortality after pancreaticoduodenectomy. Meticulous surgical technique and proper reconstruction of the pancreas are essential to prevent pancreatic fistula. Pancreaticogastrostomy is a safe method for reconstruction of the pancreas after pancreaticoduodenectomy. Regardless of pancreatic texture or duct diameter, the reconstruction is performed by passing full-thickness sutures through both the anterior and posterior sides of the pancreas. In this study, we report 39 cases of reconstruction with pancreaticogastrostomy after pancreaticoduodenectomy without mortality or pancreatic fistula.


Synthesis of polysubstituted cyclic 1,2-diketones enabled by iterative sulfoxide-mediated arylation.
A metal-free α-C-H functionalization of cyclic 1,2-diketones with aryl sulfoxides has been developed. This regioselective arylation involves nucleophilic substitution at the activated sulfoxide with a diosphenol, followed by [3,3]-sigmatropic rearrangement. This protocol can also be applied to the synthesis of polysubstituted cyclic 1,2-diketones with predictable structures by iterative arylations.


Air pollution studies.
The aim of this paper is to give an overview of the research in the area of air pollution, carried out exclusively at the Institute for Medical Research and Occupational Health and performed by the scientists of the Institute. For the past fifty years, air quality has been studied at work, in the ambient air of urban and industrial areas, and in various indoor environments without occupational exposure. Methods for sampling and measuring air pollutants have been introduced or developed and verified. The behaviour and the fate of air pollutants in the environment have also been investigated. Since the primary goal of the studies was to assess the extent of human exposure to air pollutants, the data were used to calculate the risk for various population groups. A dynamic model of exposure for various population groups relied on calculations of collected data, taking into account time spent in various microenvironments. This text describes the cooperation of the Institute with other institutions and agencies on the national and international level and outlines the current and prospective activities.


[Quality of operator's performance and associated physiological reactions in relation to stress-tolerance].
The purpose was to study operator's stress-resistance by correlating the results of work with its physiological effects associated with the sympathetic system reactions. Hard- and software Neurolab-200M was used to test 10 subjects in two experiments with different stressful conditions. Work efficiency was assessed by time for completion and accuracy of the "Manometers test" challenging the ability to perceive information and to take decision under severe time limitation. Heart rate per a minute, systolic and diastolic blood pressure were measured immediately before and during the test. According to the results of the experiments, two subjects demonstrated low stress-resistance when doing the operator's tests. Comparison of the physiological data of these and the rest subjects showed good agreement with the hypothesis that weak stress-resistance, unlike the strong one, is associated with less pronounced stress-induced sympathetic reactions.


Aurora A-Selective Inhibitor LY3295668 Leads to Dominant Mitotic Arrest, Apoptosis in Cancer Cells, and Shows Potent Preclinical Antitumor Efficacy.
Although Aurora A, B, and C kinases share high sequence similarity, especially within the kinase domain, they function distinctly in cell-cycle progression. Aurora A depletion primarily leads to mitotic spindle formation defects and consequently prometaphase arrest, whereas Aurora B/C inactivation primarily induces polyploidy from cytokinesis failure. Aurora B/C inactivation phenotypes are also epistatic to those of Aurora A, such that the concomitant inactivation of Aurora A and B, or all Aurora isoforms by nonisoform-selective Aurora inhibitors, demonstrates the Aurora B/C-dominant cytokinesis failure and polyploidy phenotypes. Several Aurora inhibitors are in clinical trials for T/B-cell lymphoma, multiple myeloma, leukemia, lung, and breast cancers. Here, we describe an Aurora A-selective inhibitor, LY3295668, which potently inhibits Aurora autophosphorylation and its kinase activity in vitro and in vivo, persistently arrests cancer cells in mitosis, and induces more profound apoptosis than Aurora B or Aurora A/B dual inhibitors without Aurora B inhibition-associated cytokinesis failure and aneuploidy. LY3295668 inhibits the growth of a broad panel of cancer cell lines, including small-cell lung and breast cancer cells. It demonstrates significant efficacy in small-cell lung cancer xenograft and patient-derived tumor preclinical models as a single agent and in combination with standard-of-care agents. LY3295668, as a highly Aurora A-selective inhibitor, may represent a preferred approach to the current pan-Aurora inhibitors as a cancer therapeutic agent.


Cognitive functioning of adolescent and young adult cannabis users in the Philadelphia Neurodevelopmental Cohort.
Cannabis use in youth is rising and has been linked to deficits in cognitive functioning. However, cognitive findings have primarily been based on small samples of users seeking treatment, and few studies have evaluated cognition in occasional cannabis users. Here, we examined 4,568 adolescents and young adults (ages 14-21 years) drawn from the Philadelphia Neurodevelopmental Cohort, a prospective, population-based study. Participants were classified as cannabis Non-Users (n = 3,401), Occasional Users (twice per week or less; n = 940), or Frequent Users (>3 times per week; n = 227). Mixed-model analyses examined main effects of cannabis use and interactions between age and cannabis use on cognitive functioning. There was a significant interaction between cannabis group and age such that adolescent (but not young adult) Frequent Users performed worse than Non-Users on measures of executive control (p = .002). Earlier age of cannabis use was associated with worse performance in executive control in Occasional Users (p = .04). Unexpectedly, Occasional Users exhibited better executive control, memory, and social cognition than Non-Users (ps < .05). Although mild executive control deficits in adolescent frequent users and a relation between early cannabis initiation and cognitive performance are partially consistent with prior research, cognitive deficits were not found in other hypothesized domains in this community-based sample. Moreover, occasional cannabis users displayed equivalent or even slightly better executive control, social-cognitive, and memory abilities compared with nonusers, suggesting complex relationships between cannabis use and cognition in youth. Longitudinal studies with community samples are needed to identify variables affecting risk and resilience to cognitive deficits associated with cannabis. (PsycINFO Database Record


Taste-Elicited Activity in Facial Muscle Regions in 5-8-Week-Old Infants.
The state of development of the sense of taste in humans during the first few months of life is only partially understood. Since taste plays a critical role in the feeding and nutrition of infants a better understanding of taste development during early life is required. Currently, information about the sense of taste in pre-verbal infants is obtained by analysis of videotaped facial expressions using the Baby FACS coding system. A potentially more objective faster procedure for assessing facial expressions not investigated in infants is electromyography (EMG). The method has been successfully used to study taste-elicited responses in the mid-face muscle regions of the levator labii and zygomaticus major of 6-9-year-olds and in a range of facial muscle regions in adults. Accordingly, this study aimed to investigate taste in young infants using EMG to 1) measure activity simultaneously in 4 facial muscle regions in response to 3 common tastants and 2) determine whether the activities of one or more muscle regions is needed to provide evidence of perception of a tastant by an infant. The results indicated that multiple facial muscle regions responded simultaneously but differentially to non-sweet and sweet tastants and recordings of activities from 3 or 4 regions simultaneously indicated that almost 100% of infants responded to the unpleasant tastes of quinine and citric acid, and 80% to sucrose.


Role of sphingolipids in oestrogen signalling in breast cancer cells: an update.
The signaling pathways activated by the steroid hormone oestrogen include a variety of cytoplasmic second messengers linked to a multitude of tissue-specific effects. In the last decade, sphingolipids and their membrane receptors were added to the list of oestrogen-activated mediators. Oestrogen triggers the sphingolipid signalling cascade in various tissues including breast cancer. Extensive research has shown that sphingolipids are the key regulatory molecules in growth factor networks. Sphingolipids can control the rate of cell proliferation and the differentiation outcome during malignant transformation. In this study, we summarise novel experimental evidences linking sphingolipids to oestrogen-activated effects, highlight the role of sphingolipids in cancer cells and discuss new avenues for future research at the intersection between oestrogen and sphingolipid signalling.


Anti-obesity effects of galangin, a pancreatic lipase inhibitor in cafeteria diet fed female rats.
Alpinia galanga Willd (Zingiberaceae) (AG) is a rhizomatous herb widely cultivated in shady regions of Malaysia, India, Indochina and Indonesia. It is used in southern India as a domestic remedy for the treatment of rheumatoid arthritis, cough, asthma, obesity, diabetes, etc. It was reported to have anti-obesity, hypoglycemic, hypolipidemic and antioxidant properties. A flavonol glycoside, galangin, was isolated from AG rhizomes. Based on its in vitro pancreatic lipase inhibitory effect, the study was further aimed to clarify whether galangin prevented obesity induced in female rats by feeding cafeteria diet (CD) for 6 weeks. The in vitro pancreatic lipase inhibitory effect of galangin was determined by measuring the release of oleic acid from triolein. For in vivo experiments, female albino rats were fed CD with or without 50 mg/kg galangin for 6 weeks. Body weight and food intake was measured at weekly intervals. On day 42, serum lipids levels were estimated and then the weight of liver and parametrial adipose tissue (PAT) was determined. The liver lipid peroxidation and triglyceride (TG) content was also estimated. The IC50 value of galangin for pancreatic lipase was 48.20 mg/mL. Galangin produced inhibition of increased body weight, energy intake and PAT weight induced by CD. In addition, galangin produced a significant decrease in serum lipids, liver weight, lipid peroxidation and accumulation of hepatic TGs. Galangin present in AG rhizomes produces anti-obesity effects in CD-fed rats; this may be mediated through its pancreatic lipase inhibitory, hypolipidemic and antioxidant activities.


Clinical implications of stenotrophomonas maltophilia resistant to trimethoprim-sulfamethoxazole: a study of 69 patients at 2 university hospitals.
We conducted a retrospective case study at 2 tertiary care centers to determine the clinical implications of trimethoprim-sulfamethoxazole resistant Stenotrophomonas maltophilia (TSRSM). Of 69 reviewed cases (mean age, 57 y; male gender, 70%), 40 (58%) were classified as infections associated with TSRSM (respiratory tract, 14; soft tissue, 11; bloodstream, 8; other sites, 7). Severe underlying comorbidities (86%) and previous antibiotic exposure (99%) were common. Cefotetan (susceptibility, 55%), chloramphenicol (49%) and ticarcillin-clavulanate (45%) showed the highest in vitro activity against TSRSM, but were seldom used for therapy (7%). Among the 40 infected cases, 8 developed sepsis disorders and 8 died. Only 1 death could be directly attributed to autopsy-proven TSRSM infection (pneumonia). McCabe score (p = 0.03) and organ dysfunction (p = 0.006) were associated with an increased risk of death in infected patients; exposure to appropriate therapy tended to be protective against death (p = 0.08). 22 infected patients were treated medically; an additional procedure was necessary to clear the infection in 18 cases (surgery, 13; catheter removal, 5). Isolation precautions were rarely exercised, even in the presence of panresistant isolates. In summary, TSRSM-related infections occurred in severely ill patients with extensive exposure to the health-care system, and often required invasive procedures for cure. Infections were directly associated with severe morbidity, and tended to have an indirect rather than a direct impact on mortality.