Modulation of Th2 responses by peptide analogues in a murine model of allergic asthma: amelioration or deterioration of the disease process depends on the Th1 or Th2 skewing characteristics of the therapeutic peptide.
Allergen-specific CD4+ Th2 cells play an important role in the immunological processes of allergic asthma. Previously we have shown that, by using the immunodominant epitope OVA323-339, peptide immunotherapy in a murine model of OVA induced allergic asthma, stimulated OVA-specific Th2 cells, and deteriorated airway hyperresponsiveness and eosinophilia. In the present study, we defined four modulatory peptide analogues of OVA323-339 with comparable MHC class II binding affinity. These peptide analogues were used for immunotherapy by s.c. injection in OVA-sensitized mice before OVA challenge. Compared with vehicle-treated mice, treatment with the Th2-skewing wild-type peptide and a Th2-skewing partial agonistic peptide (335N-A) dramatically increased airway eosinophilia upon OVA challenge. In contrast, treatment with a Th1-skewing peptide analogue (336E-A) resulted in a significant decrease in airway eosinophilia and OVA-specific IL-4 and IL-5 production. Our data show for the first time that a Th1-skewing peptide analogue of a dominant allergen epitope can modulate allergen-specific Th2 effector cells in an allergic response in vivo. Furthermore, these data suggest that the use of Th1-skewing peptides instead of wild-type peptide may improve peptide immunotherapy and may contribute to the development of a successful and safe immunotherapy for allergic patients.


Mechanisms of ErbB receptor negative regulation and relevance in cancer.
The ErbB family of receptor tyrosine kinases engages a wide variety of signaling pathways that collectively direct transcriptional programs controlling organogenesis during development and tissue maintenance in the adult. These receptors are also frequently found overexpressed or aberrantly activated in various cancers, suggesting that ErbB receptor signaling activity must be very tightly regulated. Sufficient levels of ErbB signaling are necessary to mediate tissue homeostasis, for example, but over-signaling can trigger cellular processes that contribute to cancer initiation or progression. Efforts over the last quarter century have led to a thorough understanding of the signaling pathways that are activated by these receptors and the mechanisms by which ErbB receptors engage these pathways. However, the compensatory negative regulatory mechanisms responsible for attenuating receptor activation have only more recently begun to be explored. Here we review the different known mechanisms of ErbB negative regulation, with particular emphasis on those proteins that exhibit some specificity for the ErbB family. We also describe how loss or suppression of ErbB negative regulators may contribute to tumor development, and discuss how restoration or augmentation of these pathways may represent a novel avenue for the development of ErbB-targeted therapies.


Synthesis and Characterization of Biodegradable Poly(butyl cyanoacrylate) for Drug Delivery Applications.
Poly(butyl cyanoacrylate) (PBCA) is a biodegradable and biocompatible homopolymer which is used as a carrier matrix for drug delivery systems in the pharmaceutical industry. Typically, polymerization is carried out under aqueous conditions and results in molecular weights are mostly lower than 3000 g/mol due to the instability of the high molecular weight PBCA. However, the stability of polymer excipients is a major prerequisite for drug product development in the pharmaceutical industry. In this work, a reliable polymer synthesis strategy for PBCA was designed to control the molecular weight in a nonaqueous polymerization environment. The anionic polymerization process and the impact of key synthesis parameters were investigated. The results confirmed that the previously postulated depolymerization-repolymerization process (DPRP) in the literature can be used to tailor the molecular weight of PBCA. The amount of sodium methoxide present during the polymerization proved to be the key parameter to control the DPRP and the molecular weight as desired. In addition, it was discovered that end-capping the PBCA chain suppressed the DPRP and prevented monomer release by depriving the PBCA of its living character. Thus, neat PBCA polymer with varying molecular weights determined by Advanced Polymer Chromatography™ as well as end-capped PBCA were synthesized, and the improvement of the chemical and shelf-life stability were confirmed using NMR.


Executive Function in Autism: Association with ADHD and ASD Symptoms.
There is substantial comorbidity between autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD), and there are well-documented executive functioning (EF) deficits in both populations. An important question concerns whether EF deficits in children with ASD are related to severity of ASD, ADHD, or both. We examined ADHD and ASD symptoms in relation to ratings of EF in the home and classroom. The sample comprised 64 children (55 males) diagnosed with ASD (mean age = 9.26 years; mean FSIQ = 92). Analyses indicated that parent and teacher ratings of EF (except Shift and Emotional Control) were consistently related to ADHD symptom severity, but not to ASD severity. Thus, functioning in the domains of Shift and Emotional control appear relatively spared, whereas performance in all other EF was impaired in relation to ADHD symptoms.


Trends in Tuberculosis Case Notification and Treatment Success, Haiti, 2010-2015.
Since the 2010 earthquake, tuberculosis (TB) control has been a major priority for health sector response and recovery efforts in Haiti. The goal of this study was to analyze trends in TB case notification in Haiti from the aggregate data reported by the National TB Control Program to understand the effects of such efforts. A total of 95,745 TB patients were registered for treatment in Haiti between 2010 and 2015. Three regions, the West, Artibonite, and North departments accounted for 68% of the TB cases notified during the period. Patients in the 15-34 age groups represented 53% (50,560) of all cases. Case notification rates of all forms of TB increased from 142.7/100,000 in 2010 to 153.4 in 2015, peaking at 163.4 cases/100,000 in 2013. Case notification for smear-positive pulmonary TB increased from 85.5 cases/100,000 to 105.7 cases/100,000, whereas treatment success rates remained stable at 79-80% during the period. Active TB case finding efforts in high-risk communities and the introduction of new diagnostics have contributed to increasing TB case notification trends in Haiti from 2010 to 2015. Targeted interventions and novel strategies are being implemented to reach high-risk populations and underserved communities.


Induction of sodium iodide symporter gene and molecular characterisation of HNF3 beta/FoxA2, TTF-1 and C/EBP beta in thyroid carcinoma cells.
Thyroid carcinoma cells often do not express thyroid-specific genes including sodium iodide symporter (NIS), thyroperoxidase (TPO), thyroglobulin (TG), and thyrotropin-stimulating hormone receptor (TSHR). Treatment of thyroid carcinoma cells (four papillary and two anaplastic cell lines) with histone deacetylase inhibitors (SAHA or VPA) modestly induced the expression of the NIS gene. The promoter regions of the thyroid-specific genes contained binding sites for hepatocyte nuclear factor 3 beta (HNF3 beta)/forkhead box A2 (FoxA2), thyroid transcription factor 1 (TTF-1), and CCAAT/enhancer binding protein (C/EBP beta). Quantitative reverse transcription-polymerase chain reaction (RT-PCR) showed decreased expression of HNF3 beta/FoxA2 and TTF-1 mRNA in papillary thyroid carcinoma cell lines, when compared with normal thyroid cells. Forced expression of these genes in papillary thyroid carcinoma cells inhibited their growth. Furthermore, the CpG island in the promoter region of HNF3 beta/FoxA2 was aberrantly methylated; and treatment with 5-aza-2-deoxycytidine (5-Az) induced its expression. Immunohistochemical staining showed that C/EBP beta was localised in the nucleus in normal thyroid cells but was detected in the cytoplasm in papillary thyroid carcinoma cells. Subcellular fractionation of papillary thyroid carcinoma cell lines also demonstrated high levels of expression of C/EBP beta in the cytoplasm, suggesting that a large proportion of C/EBP beta protein is inappropriately localised in the cytoplasm. In summary, these findings reveal novel abnormalities in thyroid carcinoma cells.


A retinitis pigmentosa GTPase regulator (RPGR)-deficient mouse model for X-linked retinitis pigmentosa (RP3).
The X-linked RP3 locus codes for retinitis pigmentosa GTPase regulator (RPGR), a protein of unknown function with sequence homology to the guanine nucleotide exchange factor for Ran GTPase. We created an RPGR-deficient murine model by gene knockout. In the mutant mice, cone photoreceptors exhibit ectopic localization of cone opsins in the cell body and synapses and rod photoreceptors have a reduced level of rhodopsin. Subsequently, both cone and rod photoreceptors degenerate. RPGR was found normally localized to the connecting cilia of rod and cone photoreceptors. These data point to a role for RPGR in maintaining the polarized protein distribution across the connecting cilium by facilitating directional transport or restricting redistribution. The function of RPGR is essential for the long-term maintenance of photoreceptor viability.


Cryptococcal breast abscess.
A cryptococcal abscess of the breast is uncommon and may mimic a neoplastic lesion. We describe a patient with an isolated cryptococcal infection of the breast, which was treated with oral fluconazole in combination with surgical excision. With the exception of diabetes mellitus type II, no underlying predisposing illness was identified.


Proteomics analysis of Trichoplusia ni midgut epithelial cell brush border membrane vesicles.
The insect midgut epithelium is composed of columnar, goblet, and regenerative cells. Columnar epithelial cells are the most abundant and have membrane protrusions that form the brush border membrane (BBM) on their apical side. These increase surface area available for the transport of nutrients, but also provide opportunities for interaction with xenobiotics such as pathogens, toxins and host plant allelochemicals. Recent improvements in proteomic and bioinformatics tools provided an opportunity to determine the proteome of the T. ni BBM in unprecedented detail. This study reports the identification of proteins from BBM vesicles (BBMVs) using single dimension polyacrylamide gel electrophoresis coupled with multi-dimensional protein identification technology. More than 3000 proteins were associated with the BBMV, of which 697 were predicted to possess either a signal peptide, at least one transmembrane domain or a GPI-anchor signal. Of these, bioinformatics analysis and manual curation predicted that 185 may be associated with the BBMV or epithelial cell plasma membrane. These are discussed with respect to their predicted functions, namely digestion, nutrient uptake, cell signaling, development, cell-cell interactions, and other functions. We believe this to be the most detailed proteomic analysis of the lepidopteran midgut epithelium membrane to date, which will provide information to better understand the biochemical, physiological and pathological processes taking place in the larval midgut.


A New Gal in Town: A Systematic Review of the Role of Galanin and Its Receptors in Experimental Pain.
Galanin is a neuropeptide expressed in a small percentage of sensory neurons of the dorsal root ganglia and the superficial lamina of the dorsal horn of the spinal cord. In this work, we systematically reviewed the literature regarding the role of galanin and its receptors in nociception at the spinal and supraspinal levels, as well as in chronic pain conditions. The literature search was performed in PubMed, Web of Science, Scopus, ScienceDirect, OVID, TRIP, and EMBASE using "Galanin" AND "pain" as keywords. Of the 1379 papers that were retrieved in the initial search, we included a total of 141 papers in this review. Using the ARRIVE guidelines, we verified that 89.1% of the works were of good or moderate quality. Galanin shows a differential role in pain, depending on the pain state, site of action, and concentration. Under normal settings, galanin can modulate nociceptive processing through both a pro- and anti-nociceptive action, in a dose-dependent manner. This peptide also plays a key role in chronic pain conditions and its antinociceptive action at both a spinal and supraspinal level is enhanced, reducing animals' hypersensitivity to both mechanical and thermal stimulation. Our results highlight galanin and its receptors as potential therapeutic targets in pain conditions.


[Effect of the presence of a drug in the list of supplementary drug provision on compliance to its administration by outpatients with arterial hypertension].
Aim of the study was to investigate relationship between the presence of a drug in the list of supplementary drug provision (SDP) and compliance to its consumption by outpatients with arterial hypertension as well as determination of the place of SDP in a row of other factors affecting compliance to treatment. Methods. Patients (men and women) older than 18 years with initial level of office systolic arterial pressure (AP) 140-179 mm Hg and diastolic AP up to 100 mm Hg who visited regional internist. The study was conducted at the base of 82 Moscow polyclinics with participation of 185 physicians and 5474 patients. In all patients besides general clinical examination with office AP measurement calculation of body mass index and assessment of risk factors and concomitant therapy were carried out. All patients assessed themselves their self feeling with the use of visual-analog scale (VAS). Compliance of patients to antihypertensive therapy was evaluated with the help of the Moriski - Green test. Fact of continuous use of antihypertensive drugs received by patients within framework of the SDP system was necessarily obligatory. For final analysis 4816 ambulatory cards were selected. Results. Portion of patients with low compliance to therapy was greatly than that of patients with high compliance to therapy (61.1 vs. 38.9%, respectively, p=0.00001). Inclusion into analysis of additional factor (presence of CHD) reduced contribution of SDP to compliance to 25%, but it remained as before significant (p<0.0007). However addition to these factors of other parameters such as presence of diabetes mellitus or tonometer at home completely leveled effect of SDP on compliance to therapy (p<0.12). Conclusion. Presence of drugs in the SDP list significantly elevates compliance to therapy. However SDP does not appear the only independent predictor of high compliance. If SDP is considered together with other determining factors (presence of concomitant IHD and diabete, readiness to spend money for tonometer) its role as independent factor of high compliance is diminished and loses significance.


Exogenous heat shock protein-70 inhibits cigarette smoke-induced intimal thickening.
Cigarette smoke is associated with increased carotid intimal thickening or stroke. Preliminary work showed that exposure to smoke resulted in a 4.5-fold reduction of heat shock protein-70 (HSP70) expression in spleens of mice using gene microarray analysis. In the current study, we investigated the role of extracellular HSP70 in carotid intimal thickening of mice exposed to cigarette smoke. Intimal thickening was induced by placement of a cuff around the right carotid artery of mice. Cuff injury resulted in increased HSP70 mRNA expression in carotid arteries that persisted for 21 days. Cigarette smoke exposure decreased arterial HSP70 expression and significantly increased intimal thickening compared with mice exposed to air. Treatment of mice exposed to cigarette smoke with intravenous recombinant HSP70 attenuated intimal thickening through reduced phosphorylated extracellular signal-regulated kinase (pERK) expression in the arterial wall. In vitro experiments with rat aortic smooth muscle cells confirmed that recombinant HSP70 decreases pERK and proliferating cell nuclear antigen (PCNA) expression in cells exposed to cigarette smoke extract and H(2)O(2). Our study suggests that decreased expression of arterial HSP70 is an important mechanism by which exposure to cigarette smoke augments intimal thickening. The effects of recombinant HSP70 suggest a role for extracellular HSP70.


Some fluid mechanical constraints on crystallization and recharge within sills.
The injection of hot magma into a sill can lead to heating and melting of the walls and roof of the reservoir while the injected magma cools and crystallizes. If the crystals are relatively dense, they will try to sediment from the injected magma to form a cumulate layer. In this cumulate layer, the crystals form a porous framework which traps the melt as it is built up. As the melt within the sill continually cools and precipitates dense crystals, there will be a gradual reduction in the density of the remaining silicate liquid. As a result, the melt which is progressively trapped in the pore space of the cumulate layer will become stably stratified in density. Using an idealized model of the fluid mechanical and thermodynamical principles, we explore some of the controls on the thickness and density stratification of cumulate layers following replenishment of a sill-like magma chamber. We show the balance between jamming of the crystal laden melt to form a homogeneous layer and the formation of a stratified cumulate zone depends on the cooling time scale compared to the sedimentation time scale. A key finding is that the composition and stratification in a packed crystal-melt suspension and the associated cumulate layer formed by cooling an intrusion of hot melt injected into the crust may have considerable variability, depending on the properties of the overlying roof melt and the size and hence fall speed of crystals which form in the melt. This article is part of the Theo Murphy meeting issue 'Magma reservoir architecture and dynamics'.


Systemic and local effects of metformin administration in patients with polycystic ovary syndrome (PCOS): relationship to the ovulatory response.
Several data have demonstrated the efficacy of metformin in inducing ovulation in patients with polycystic ovary syndrome (PCOS), however, the exact mechanism by which this drug acts remains unknown. The aim of the present study was to evaluate whether the efficacy of the drug in patients with PCOS is related to a systemic hormonal-metabolic improvement, or to a local action on the ovary. Twenty-four normal weight patients with PCOS, who were treated with metformin, were enrolled. Of these, 12 subjects were anovulatory (Group A1), whereas the other 12 were ovulatory but had failed to conceive (Group A2). A further 24 untreated subjects who were scheduled for laparoscopic surgery were enrolled as controls, 12 anovulatory patients with PCOS scheduled for laparoscopic myomectomy (Group B1) and a further 12 non-PCOS participants were scheduled for diagnostic laparoscopy (Group B2). Clinical assessments and biochemical evaluations in blood and antral follicular fluid were performed in each participant. In 1/12 and 9/12 participants from Groups A1 and A2, respectively, the ovarian morphology was changed, and a significant (P < 0.05) reduction in the ovarian dimensions was observed only in Group A2. In both of these groups, and without difference between them, serum androgens and indices of insulin resistance improved significantly (P < 0.05) after metformin treatment. On the other hand, significant differences (P < 0.05) between the two groups were detected with respect to the same biochemical parameters in antral follicular fluid. In Groups A1 and A2, levels of androgens and indices of insulin resistance in the antral follicular fluid were significantly (P < 0.05) better than in Group B1, but worse than in Group B2. Irrespective of its systemic effects, the efficacy of metformin in the induction of ovulation is probably due to a direct action on the ovary, and the ovulatory response to the drug seems to be related to local sensitivity or resistance to the drug.


[CSF levels and diagnostic utility of cerebrospinal fluid beta2-microglobulin].
CSF levels of beta2-microglobulin reflect immune activation and lymphoid cell turnover in CNS. There were proposed as a reliable marker of lymphoproliferative disorders in central nervous system in viral infections, inflammatory diseases, autoimmune diseases and malignancies. The aims of this study were to measure beta2-microglobulin on the automate Vidas of bioMérieux in 122 paired CSF and serum from control patients. We evaluated whether or not the elevated levels beta2-microglobulin in CSF can be a useful marker for diagnosis of lymphoproliferative disorders in 108 patients with neurological diseases. The concentrations of beta2-microglobulin in the CSF and sera from control patients were respectively 1.3 +/- 0.5 mg/L and 2 +/- 0.6 mg/L. The normal CSF to serum beta2-microglobulin ratio was 0.6 +/- 0.19. A CSF to serum beta2-microglobulin ratio greater than 1 was closely associated with intrathecal synthesis beta2-microglobulin in CNS lymphoproliferative disorders. Elevation of CSF beta2-microglobulin ratio is a sensitive marker of central nervous system disease activity by infiltrating lymphocytes in intracranial lymphomas (10/10) and paraneoplastic neurological syndromes (2/3).


Vertebrate-type and plant-type ferredoxins: crystal structure comparison and electron transfer pathway modelling.
Crystallographic analysis of a fully functional, truncated bovine adrenodoxin, Adx(4-108), has revealed the structure of a vertebrate-type [2Fe-2S] ferredoxin at high resolution. Adrenodoxin is involved in steroid hormone biosythesis in adrenal gland mitochondria by transferring electrons from adrenodoxin reductase to different cytochromes P450. Plant-type [2Fe-2S] ferredoxins interact with photosystem I and a diverse set of reductases.A systematic structural comparison of Adx(4-108) with plant-type ferredoxins which share about 20 % sequence identity yields these results. (1) The ferredoxins of both types are partitioned into a large, strictly conserved core domain bearing the [2Fe-2S] cluster and a smaller interaction domain which is structurally different for both subfamilies. (2) In both types, residues involved in interactions with reductase are located at similar positions on the molecular surface and coupled to the [2Fe-2S] cluster via structurally equivalent hydrogen bonds. (3) The accessibility of the [2Fe-2S] cluster differs between Adx(4-108) and the plant-type ferredoxins where a solvent funnel leads from the surface to the cluster. (4) All ferredoxins are negative monopoles with a clear charge separation into two compartments, and all resulting dipoles but one point into a narrow cone located in between the interaction domain and the [2Fe-2S] cluster, possibly controlling predocking movements during interactions with redox partners. (5) Model calculations suggest that FE1 is the origin of electron transfer pathways to the surface in all analyzed [2Fe-2S] ferredoxins and that additional transfer probability for electrons tunneling from the more buried FE2 to the cysteine residue in position 92 of Adx is present in some.


Expression of cluster differentiation-44 stem cell marker in grades of oral epithelial dysplasia: A preliminary study.
Oral cancer is one among the alarming diseases related to oral cavity. Its prevalence and incidence have increased in many folds, in the past decade. This has led the investigators to find the preliminary stages and related early evaluating methods to restrain it. Few clinical lesions such as leukoplakia, erythroplakia, oral submucous fibrosis and lichen planus reflected malignant changes. These premalignant disorders provided scope to assess the underlying cellular and molecular events, which shall be helpful in early detection, aggressiveness and prognosis of the patient. Forty formalin fixed, paraffin embedded blocks were utilized and evenly subdivided into Group I - control tissue, Group II - mild epithelial dysplasia, Group III - moderate epithelial dysplasia and Group IV - severe epithelial dysplasia. The study group was categorized based on the WHO classification of dysplasia 2005. Routine staining was performed to reconfirm the diagnosis of all the samples. Simultaneously, immunohistochemical staining was done with cluster differentiation-44 (CD44) antibody. Positive cells were counted on 10 representative fields with a minimum of 100 cells per field using ×20. Comparison of four groups with respective to number of positive cells was done using Kruskal-Wallis ANOVA test. Pair-wise comparison of three grades of oral epithelial dysplasia and the controls was done using Mann-Whitney U test. The mean of Group I is 745.50, Group II is 665.20, Group III is 530.10 and Group IV is 322.90. A statistically significant P = 0.00001 was ascertained on comparison of the mean between the groups. CD44, a cell membrane marker could help in cell adhesion and cell-cell interactions. Loss of CD44 expression enhances the binding of the growth factors with their principle receptors that enhances the cellular proliferation. It can be used as a prognostic marker for identifying the rate of malignant transformation in these disorders.


Developmental and contextual influences on autonomic reactivity in young children.
Studies of cardiovascular reactivity in young children have generally employed integrated, physiologically complex measures, such as heart rate and blood pressure, which are subject to the multiple influences of factors such as blood volume, hematologic status, thermoregulation, and autonomic nervous system (ANS) tone. Reactivity studies in children have rarely employed more differentiated, proximal measures of autonomic function capable of discerning the independent effects of sympathetic and parasympathetic responses. We describe 1) the development, validity, and reliability of a psychobiology protocol assessing autonomic reactivity to challenge in 3- to 8-year-old children; 2) the influences of age, gender, and study context on autonomic measures; and 3) the distributions of reactivity measures in a normative sample of children and the prevalences of discrete autonomic profiles. Preejection period (PEP) and respiratory sinus arrythmia (RSA) were measured as indices of sympathetic and parasympathetic nervous system reactivity, respectively, and autonomic profiles were created to offer summative indices of PEP and RSA response. Results confirmed the protocol's validity and reliability, and showed differences in autonomic reactivity by age and study context, but not by gender. The studies' findings offer guidelines for future research on autonomic reactivity in middle childhood and support the feasibility of examining sympathetic and parasympathetic responses to challenge in 3- to 8-year-old children.


The polio model. Does it apply to polio?
According to the polio model, severity of disease increases with age at infection. Firstborn children and people belonging to small families are generally infected later and should accordingly have a higher risk of severe polio. However, this model does contradict other explanations of severity of childhood infections including the intensive-exposure model. To evaluate the deductions from the polio model we performed a study based on medical records from 5590 historical polio cases from the county of Copenhagen 1940-1953. The relative risk (RR) of polio according to age, birth order and sibship size was evaluated using census data from 1940 and 1950. Severity of polio measured as frequency of paralysis or mortality did not show a steady increase with age, but a U-shaped curve being highest for the youngest as well as the oldest patients. The incidence of polio and paralytic polio was higher in families with several children compared with single children (RR = 1.13, 95% CI : 1.0-1.3). Furthermore, the incidence was higher in later-born children (P(trend) < 0.0001). However, as predicted from the intensive-exposure model, second-born children aged 1-4 years in two-child families had a higher risk of paralytic polio than first-born children (RR = 1.47, 95% CI : 1.1-2.0), whereas the opposite relationship was found for those aged > or = 5 years (RR = 0.65, 95% CI : 0.5-0.9). The polio model's prediction about the impact of age, sibship size and birth order on polio incidence and severity found only limited support. A model emphasizing intensity of exposure as a risk factor for severity may account better for the epidemiology of polio infection.


Facile radiolabeling optimization process via design of experiments and an intelligent optimization algorithm: Application for omeprazole radioiodination.
The major uses of radiopharmaceuticals (RP) in clinical areas are diagnosis and/or therapy. The present study aimed to utilize the application of fractional factorial design analysis (FFDA) coupled with particle swarm optimization algorithm (PSO) to assess the optimization of RP production process. In this regard, omeprazole (OMP), which is gastric parietal cell proton pump inhibitor (PPI), was radiolabeled with iodine-125 (125 I) isotope in order to be used as a radiotracer for stomach imaging. Different factors that affect radiolabeling process were studied. According to the proposed design, just 16 experimental runs of radiolabeling process were performed using the extremes of each factor. In addition, one run was executed at the mean point of each factor. Undesirable maximum radiolabeling yield (RY) of radioiodinated omeprazole (125 I-OMP) was deduced from application of FFDA (88.4%). Furthermore, after applying PSO with changing limits of one factor, the maximum RY of 125 I-OMP was found to be 93.78%. Moreover, the practically verification from optimum conditions, which obtained from PSO, was found to give an RY of 93.99%. Overall, the findings of this study confirmed the potential use of that hybrid design for optimization of radiolabeling processes.


The effect of plasma homocysteine levels on clinical outcomes of patients with acute lung injury/acute respiratory distress syndrome.
Several reports have shown that homocysteine promotes thrombosis by disturbing the procoagulant-anticoagulant balance, whereas alterations in coagulation and fibrinolysis have been suggested as important pathogenetic and prognostic determinants of mortality in acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). The objective of the study was to evaluate the effect of plasma homocysteine levels on the outcomes of patients with ALI/ARDS. Sixty-nine consecutive ventilated patients with ALI/ARDS were studied. Blood samples were drawn within 3 days of clinical recognition of ARDS. Measurement of plasma homocysteine, vitamin B12, folate, creatinine, protein C and plasminogen-activator inhibitor-1 antigen levels, and genotyping of the methylenetetrahydrofolate reductase gene C677T and A1298C polymorphisms were carried out. The primary outcomes were 28- and 90-day mortality, whereas secondary outcomes included nonpulmonary organ failure-free days, liberation from mechanical ventilation up to day 28, and ventilator-free days during the 28 days after enrollment. In the multivariable analysis, plasma homocysteine concentration adjusted for age, Acute Physiology and Chronic Health Evaluation II score, methylenetetrahydrofolate reductase C677T and A1298C polymorphisms, and levels of plasminogen-activator inhibitor-1 antigen, protein C, creatinine, vitamin B12, and folate was not found to affect significantly mortality at 28 and 90 days (P = 0.39 and P = 0.83, respectively), days without organ failure besides lungs (P = 0.38), the probability of being free from mechanical ventilation at day 28 (P = 0.63), and days without ventilation assistance (P = 0.73). Our data suggest that increased plasma homocysteine levels, either alone or in synergy with other thrombophilic risk factors, do not seem to adversely affect the prognosis in patients with ALI/ARDS.


The effects of repeated administration of various chelating agents on the removal of strontium from the mouse.
The effects of repeated ip administration of diethylenetriaminepentaacetic acid (DTPA), Kryptofix 222, 1,4,7,10,13,16-hexaoxacyclooctadecane (18-crown-6), ethylenglycol-bis-(beta-amino-ethylether)-N,N'-tetraacetic acid (EGTA), and Kryptofix 5 on the distribution and excretion of sc-injected strontium were investigated in male Swiss mice. Groups of 20 animals received 95 mg strontium nitrate/kg, and 10 min later ip treatment with one of the chelators or 0.9% saline was initiated and continued for 10 d. The animals were housed in plastic metabolism cages, and urine and feces were collected daily during the period of treatment. At the end of this period, the animals were killed and the concentration of strontium determined in their tissues. Only Kryptofix 5 and EGTA significantly increased the amount of strontium excreted into feces, whereas none of the chelators significantly enhanced the urinary elimination of strontium. Treatment with Kryptofix 5 significantly decreased the concentration of strontium in all tissues analyzed. Kryptofix 5 was the most effective agent of those tested in the removal of strontium after a single dose of strontium nitrate.


Mass and Stiffness Impact on the Middle Ear and the Cochlear Partition.
Mass and stiffness affect on the peculiar characteristics of transmission of the middle ear and the distinctive behavior of the cochlear mechanics. Applying the principle of the mass and stiffness, the band-pass characteristic transfer function of the middle ear has been explained. The greatest transfer function of the middle ear, approximately 24-29 dB, is observed at 1-2 kHz in both cat and human species. However, at lower frequencies, the transfer function was disturbed by the stiffness of the middle ear primarily due to middle ear cavity. At higher frequencies, the transfer function was disturbed by the stiffness of the middle ear primarily due to middle ear bones. Several examples, such as an acoustic reflex, otitis media, and otosclerosis are discussed. For understanding the traveling wave of the basilar membrane, different place tuning at certain stimulus frequencies, contrastingly shaped basilar membrane to the cochlear duct, and the structural and physical characteristics of the whole cochlear partition were reviewed in terms of changing width, mass, and stiffness from the base to apex. Being about ten times wider, more massive, and one hundredfold stiffer at the base than the apex, the nature of the cochlear partition to absorb high-frequency energy changes in fluid pressure declines toward the apex. Consequently, at the base of the cochlea, high frequencies stimuli are decoded while low frequencies stimuli are decoded at the apex of the cochlea. Due to these characteristics of the cochlear partition, the direction of the traveling wave was also proved to be in the fashion of base-to-apex always.


Resistance to Growth of Molds for Wood Modified with Hydrophobic Hybrid Silica Gel Containing Copper Amine Complexes.
Complexation copper with amine provides an effective strategy for fixation copper in wood, while hydrophobic modification improves the dimensional stability of wood. Thus, a combination of complexation and hydrophobization is expected to enhance the efficiency of copper-based biocides. In this study, hydrophobic hybrid silica gel containing copper amine complexes (MACu) was prepared through an in situ sol-gel process in wood using methyltriethoxysilane (MTES), 3-amino-propyltriethoxysilane (APTES), and copper chloride. The resistance to growth of molds for MACu modified wood (Populus tomentosa) was measured according to ASTM D3273-16. A leaching resistance test was carried out in accordance with AWPA E11-16. The results showed that only Aspergillus niger covered the surface of untreated wood blocks and no mold grew on the MACu surface even after the leaching test. MACu xerogel and MACu wood were further characterized by SEM-EDS, FTIR, and XPS. A possible schematic diagram of the reaction mechanism was proposed to explain the high-efficiency anti-mold performance of MACu wood.


Coordination between Surface Lattice Resonances of Poly(glycidyl Methacrylate) Line Array and Surface Plasmon Resonances of CdS Quantum on Silicon Surface.
In this work, a unique hybrid system is proposed for one-dimensional gratings comprising of poly(glycidyl methacrylate) (PGMA) brushes and CdS quantum dots (CQDs). Generally, the emission of QDs is too weak to be observed in a dry state. Plasmonic resonances of the grating structures can be used to enhance the light emission or absorption of CQDs. The interaction between PGMA plasmonic nanostructures and inorganic CQDs plays a crucial role in engineering the light harvest, notably for optoelectronic applications. Extinction measurements of the hybrid system consisting of a PGMA grating and CQDs are reported. We designed one-dimensional gratings with various resolutions to tune the absorptance peaks of grating. PGMA grating grafted from a 1.5 µm resolution of trench arrays of photoresist exhibited absorptance peak at 395 nm, close to the absorption peak of CQDs, resulting in the photoluminescence enhancement of CQDs on the grating due to high charge carriers' recombination rate. Generally, the emission of quantum dots occurs under irradiation at characteristic wavelengths. Immobilizing QDs on the grating facilitates the emission of QDs under irradiation of full-wavelength light. Furthermore, the PGMA gratings with CQDs were immersed in various solvents to change the geometries resulting the shift of absorptance peak of grating. The proposed method could be applied for sensing the nature of the surrounding media and vice versa, as well as for various media of solvents.


Highly reflective Er-doped ZnO thin-film coating for application in a UV optical ring resonator.
We achieved doping-induced optical variation in Erbium-doped ZnO (EZO) that may prove to be a promising material for use in optical ring resonators. EZO thin-film samples were deposited on n-type Si substrate via the sol-gel spin-coating technique followed by annealing in air at 500 °C. The doping-induced morphological variations of the deposited thin film were characterized using x-ray diffraction, ellipsometry, scanning electron microscopy and energy dispersive x-ray spectroscopy. Further, in order to establish the suitability of EZO for optical applications, detailed optical analysis was performed that exhibited that 1 mol% Er-doped ZnO may prove to be suitable material. Finally, a ring resonator design has been proposed using 1 mol% EZO thin film. The proposed structure was simulated using the MODE tool by Lumerical solutions. The Eigenmode Solver has been used to simulate and calculate the effective refractive index, group velocity, propagation constant β, dispersion and bending losses for a wavelength region of 200 nm to 900 nm. Simplified expressions for the free spectral range, full-width at half-maximum and quality factor have been derived and validated by the simulated data for the proposed ring resonator.


Effect of Poly-L-Lactic Acid Mesh Augmentation on Cyclic Gap Formation in Transosseous Patellar Tendon Repair: A Biomechanical Study.
No previous study has investigated poly-L-lactic acid (PLLA) surgical mesh augmentation in the repair of inferior pole patellar tendon rupture. We compared the biomechanical properties of transosseous patellar tendon repair with PLLA surgical mesh augmentation to transosseous repair without augmentation. Ten matched pairs of cadaveric knees were used. Specimens in each pair were randomized to undergo the transosseous technique alone or the transosseous technique augmented with a PLLA surgical mesh. An inferior pole patellar tendon rupture was simulated and the repair procedure was performed. Specimens were cyclically loaded for 500 cycles. Gap formation was measured using two sensors placed medial and lateral to the repair site. After cyclic loading, load to failure was determined by pulling the tendon at a constant rate until a sudden decrease in load occurred. The primary outcome measure was cyclic gap formation at the medial and lateral sensors. Compared with controls, specimens that underwent PLLA mesh-augmented repair had significantly lower medial gap formation at all testing intervals up to 500 cycles (p < 0.05) and significantly lower lateral gap formation at all testing intervals from 10 to 500 cycles (p < 0.05). Transosseous patellar tendon repair augmented with a PLLA woven mesh device provided significantly greater resistance to gap formation compared with transosseous repair alone. These results suggest that PLLA mesh augmentation of the transosseous technique is biomechanically effective for patellar tendon repair.


Sequential Localizing and Mapping: A Navigation Strategy via Enhanced Subsumption Architecture.
In this paper, we present a navigation strategy exclusively designed for social robots with limited sensors for applications in homes. The overall system integrates a reactive design based on subsumption architecture and a knowledge system with learning capabilities. The component of the system includes several modules, such as doorway detection and room localization via convolutional neural network (CNN), avoiding obstacles via reinforcement learning, passing the doorway via Canny edge's detection, building an abstract map called a Directional Semantic Topological Map (DST-Map) within the knowledge system, and other predefined layers within the subsumption architecture. The individual modules and the overall system are evaluated in a virtual environment using Webots simulator.


Sociocultural practices influencing under five nutritional status in an urban community in Osun State, Nigeria.
Three hundred and forty four preschool children from Ilare district of Ife Central Local Government Area of Osun State, Nigeria were assessed for nutritional status using selected and sensitive anthropometric techniques. The sociocultural practices of the parents were also examined. Approximately 53.8% and 54.7% of the children were identified to be malnourished and stunted respectively. The socioeconomic situation of the family was identified to have a significant influence on the child's nutritional status. Female children were observed not to be as adequately nourished as their male counterparts. However parity and food taboo had no significant influence on the child's nutritional status. The need for improvement in the socioeconomic status of the family and education of the community on the importance of female nutrition are discussed.


Curative efficacy of norfloxacin in falciparum malaria.
Fifteen patients of uncomplicated falciparum malaria from Delhi were treated with norfloxacin (10 with 400 mg, 5 with 800 mg, both twice daily) for 3 days and the response was measured according to the WHO extended in vivo test criteria. The lower dose produced S response in two, RII response in five and RIII response in three patients, while the higher dose produced S response in four and RI response in one patient. In patients with S or RI response, the parasite clearance time was 68.6 +/- 9.1 h the defervescence time being 48 h. Thus, norfloxacin did reveal in vivo activity in falciparum malaria, but a dose of 400 mg twice daily proved to be curative only in a small percentage of cases and not consistently. Nausea and bitter taste were the only side effects noted in two patients.


Insulin-like growth factor (IGF)-I and IGF binding proteins axis in diabetes mellitus.
Increasing evidence suggests an important role of the insulin-like growth factor (IGF)-IGF binding protein (IGFBP) axis in the maintenance of normal glucose and lipid metabolism. Significant changes occur in the local IGF-I-IGFBPs environment in response to the diabetic milieu. A significant reduction of serum IGF-I levels was observed in patients with type 1 diabetes mellitus (T1DM). Inversely, considerably increased serum levels of IGF-I and IGFBP-3 levels were detected in individuals with glucose intolerance including T2DM. Recently, several prospective studies indicated that baseline levels of IGF-I and IGFBPs are associated with the development of diabetes. These findings suggest that disturbances in insulin and IGF-I-IGFBP axis can affect the development of glucose intolerance including diabetes.


Synthesis and biological activity of 3-vinylthio- and 3-vinylthiomethylcephem derivatives.
The synthesis and biological properties of some 3-vinylthio- and 3-vinylthiomethylcephem derivatives are described. Both series possess potent antibacterial activity. Among them, 3-[(Z)-2-cyanovinylthiomethyl]cephem derivative was found to have an expanded antibacterial spectrum.


Social cognition in schizophrenic patients: the effect of semantic content and emotional prosody in the comprehension of emotional discourse.
The recognition of the emotion expressed during conversation relies on the integration of both semantic processing and decoding of emotional prosody. The integration of both types of elements is necessary for social interaction. No study has investigated how these processes are impaired in patients with schizophrenia during the comprehension of an emotional speech. Since patients with schizophrenia have difficulty in daily interactions, it would be of great interest to investigate how these processes are impaired. We tested the hypothesis that patients present lesser performances regarding both semantic and emotional prosodic processes during emotional speech comprehension compared with healthy participants. The paradigm is based on sentences built with emotional (anger, happiness, or sadness) semantic content uttered with or without congruent emotional prosody. The study participants had to decide with which of the emotional categories each sentence corresponded. Patients performed significantly worse than their matched controls, even in the presence of emotional prosody, showing that their ability to understand emotional semantic content was impaired. Although prosody improved performances in both groups, it benefited the patients more than the controls. Patients exhibited both impaired semantic and emotional prosodic comprehensions. However, they took greater advantage of emotional prosody adjunction than healthy participants. Consequently, focusing on emotional prosody during carrying may improve social communication.


Occupational pesticide use and self-reported olfactory impairment in US farmers.
Pesticide exposure may impair human olfaction, but empirical evidence is limited. We examined associations between occupational use of 50 specific pesticides and olfactory impairment, both self-reported, among 20 409 participants in the Agricultural Health Study, a prospective cohort of pesticide applicators (mostly farmers, 97% male). We used logistic regression models to estimate odds ratios (OR) and 95% confidence intervals (CI) for associations between pesticide use at enrolment (1993-1997) and olfactory impairment reported two decades later (2013-2016), adjusting for baseline covariates. About 10% of participants reported olfactory impairment. The overall cumulative days of any pesticide use at enrolment were associated with a higher odds of reporting olfactory impairment (OR (highest vs lowest quartile): 1.17 (95% CI: 1.02 to 1.34), p-trend = 0.003). In the analyses of 50 specific pesticides, ever-use of 20 pesticides showed modest associations with olfactory impairment, with ORs ranging from 1.11 to 1.33. Of these, higher lifetime days of use of 12 pesticides were associated with higher odds of olfactory impairment compared with never use (p-trend ≤ 0.05), including two organochlorine insecticides (dichlorodiphenyltrichloroethane and lindane), two organophosphate insecticides (diazinon and malathion), permethrin, the fungicide captan and six herbicides (glyphosate, petroleum distillates, 2,4-dichlorophenoxyacetic acid, 2,4,5-trichlorophenoxyacetic acid and metribuzin), although many of these did not exhibit clear, monotonic exposure-response patterns. Overall, we found relatively broad associations between pesticides and olfactory impairment, involving many individual pesticides and covering several chemical classes, suggesting that pesticides could affect olfaction through multiple pathways. Future epidemiological studies with objective measurement of olfaction are required to confirm these findings.


Challenging issues in tuberculosis in solid organ transplantation.
Solid organ transplant (SOT) recipients are at risk for opportunistic infections including tuberculosis. Although guidelines on the management of latent tuberculosis and active tuberculosis are available, there remain a number of clinical areas with limited guidance. We discuss challenges in the diagnosis, management, and treatment of latent and active tuberculosis in SOT candidates and recipients who reside in low-tuberculosis-prevalence areas. We discuss the diagnosis of latent tuberculosis in SOT candidates/recipients using tuberculin skin tests and interferon-γ release assays and risk stratification of SOT candidates/recipients that would identify individuals at high risk for latent tuberculosis despite negative test results. Through a careful review of posttransplant tuberculosis cases, we identify a history of treated tuberculosis in SOT recipients as a risk factor for development of posttransplant active tuberculosis. Finally, we include comparisons of recommendations by several large transplant organizations and identify areas for future research.


Can we predict mortality in patients with necrotizing fasciitis using conventional scoring systems?
This study compared the predictive accuracy of four scoring systems, namely Acute Physiology and Chronic Health Evaluation II (APACHE II), Sequential Organ Failure Assessment (SOFA), Simplified Acute Physiology Score II (SAPS II), and Mortality in Emergency Department (MEDS), for estimating prognosis in patients with necrotizing fasciitis. Seventy-four patients who presented with necrotizing fasciitis were retrospectively examined. The ability of the scoring systems to predict mortality was assessed by comparing the estimated mortality rates in mortality groups (survivors/non-survivors), and mortality rates among survivors and non-survivors with an estimated mortality of >10%, 30%, and 50% in the scoring systems were compared in pairs. Estimated mortality rates in the survivor and non-survivor groups were different for all the scoring systems. The estimated mortality rates of APACHE II and SAPS II were much closer to the actual mortality rates than the other two scoring systems. When the predicted mortality rates were analyzed as limits for a mortality risk, the predicted mortality rate by APACHE II was superior to that by SAPS II. The studied scoring systems had significantly higher predicted mortality rates in non-survivors than in survivors; however, they all underestimated the mortality rate. APACHE II and SAPS II were relatively superior for estimating mortality in patients with necrotizing fasciitis. APACHE II rather than the other scoring systems should be currently used.


Exploring the influence of high order transverse modes on the temporal dynamics in an optically pumped mode-locked semiconductor disk laser.
We quantitatively investigate the influence of high-order transverse modes on the self-mode locking (SML) in an optically pumped semiconductor laser (OPSL) with a nearly hemispherical cavity. A physical aperture is inserted into the cavity to manipulate the excitation of high-order transverse modes. Experimental measurements reveal that the laser is operated in a well-behaved SML state with the existence of the TEM(0,0) mode and the first high-order transverse mode. While more high-order transverse modes are excited, it is found that the pulse train is modulated by more beating frequencies of transverse modes. The temporal behavior becomes the random dynamics when too many high-order transverse modes are excited. We observe that the temporal trace exhibits an intermittent mode-locked state in the absence of high-order transverse modes.


Mayer-Rokitansky-Kuster-Hauser syndrome type II: A rare case.
Mayer-Rokitansky-Kuster-Hauser (MRKH) is a malformation complex comprising absent vagina and absent or rudimentary uterus. MRKH syndrome may be attributed to an initial affection of the intermediate mesoderm consequently leading (by the end of the 4(th) week of fetal life) to an alteration of the blastema of the cervicothoracicsomites and the pronephricducts. These latter subsequently induce the differentiation of the mesonephric and then the Wolffian and Mullerian ducts. There are very sparse such cases reported. We present a case of type II MRKH or Mullerian renal cervical somite association (i.e., Mullerian duct aplasia, renal dysplasia, and cervical somite anomalies).


Topical interests and the mitigation of search engine bias.
Search engines have become key media for our scientific, economic, and social activities by enabling people to access information on the web despite its size and complexity. On the down side, search engines bias the traffic of users according to their page ranking strategies, and it has been argued that they create a vicious cycle that amplifies the dominance of established and already popular sites. This bias could lead to a dangerous monopoly of information. We show that, contrary to intuition, empirical data do not support this conclusion; popular sites receive far less traffic than predicted. We discuss a model that accurately predicts traffic data patterns by taking into consideration the topical interests of users and their searching behavior in addition to the way search engines rank pages. The heterogeneity of user interests explains the observed mitigation of search engines' popularity bias.


Manipulation of p-/n-Type Thermoelectric Thin Films through a Layer-by-Layer Assembled Carbonaceous Multilayer Structure.
Recently, with the miniaturization of electronic devices, problems with regard to the size and capacity of batteries have arisen. Energy harvesting is receiving significant attention to solve these problems. In particular, the thermoelectric generator (TEG) is being studied for its ability to harvest waste heat energy. However, studies on organic TEGs conducted thus far have mostly used conductive polymers, making the application range of TEGs relatively narrow. In this study, we fabricated organic TEGs using carbonaceous nanomaterials (i.e., graphene nanoplatelet (GNP) and single-walled carbon nanotube (SWNT)) with polyelectrolytes (i.e., poly(vinyl alcohol) (PVA) and poly (diallyldimethyl ammonium chloride) (PDDA)) via layer-by-layer (LbL) coating on polymeric substrates. The thermoelectric performance of the carbonaceous multilayer structure was measured, and it was confirmed that the thermoelectric performance of the TEG in this study was not significantly different from that of the existing organic TEG fabricated using the conductive polymers. The 10 bilayer SWNT thin films with polyelectrolyte exhibited a thermopower of -14 μV·K-1 and a power factor of 25 μW·m-1K-2. Moreover, by simply changing the electrolyte, p- or n-type TEGs could be easily fabricated with carbonaceous nanomaterials via the LbL process. Also, by just changing the electrolyte, p- or n-type of TEGs could be easily fabricated with carbonaceous nanomaterials with a layer-by-layer process.


Detection and characterization of ceramide-1-phosphate phosphatase activity in rat liver plasma membrane.
A calcium-dependent ceramide (Cer) kinase was recently detected in human leukemia (HL-60) cells (Kolesnick, R.N., and Hemer, M.R. (1990) J. Biol. Chem. 265, 18803-18808) where it may function in terminating the regulatory effects of Cer, and in synaptic vesicles (Bajjalieh, S. M., Martin, T. F. J., and Floor, E. (1989) J. Biol. Chem. 264, 14354-14360). We now demonstrate that the addition of both Cer-1-phosphate (Cer-1-P) and a short-acyl chain analog of Cer-1-P,N-hexanoylsphingosine-1-phosphate (C6-Cer-1-P) to cultured cells and a variety of subcellular fractions results in rapid degradation to Cer and C6-Cer, respectively. The Cer-1-P phosphatase activity is enriched in a rat liver plasma membrane fraction and appears to be distinct from the phosphatase that hydrolyzes phosphatidic acid (PA), PA phosphohydrolase, as shown by the difference in sensitivity of Cer-1-P and PA hydrolysis to propranolol, detergent, and heat treatment. Moreover, the Km of Cer-1-P hydrolysis is 10-fold lower than the Km of PA hydrolysis in plasma membrane. PA is a noncompetitive inhibitor of Cer-1-P hydrolysis, with an inhibition constant 1-1.5-fold higher than the Km of Cer-1-P hydrolysis. In contrast, Cer-1-P does not inhibit PA hydrolysis. Finally, we describe the synthesis of a novel analog of Cer-1-P which is not hydrolyzed in vitro and in vivo and is internalized in cultured cells by endocytosis. These results are discussed in relation to the possible roles of Cer-1-P in regulating intracellular levels of Cer.


Stenting for choledocholithiasis: temporizing or therapeutic?
Maxton and colleagues report their experience using biliary endoprostheses for treatment of failed common bile duct stone clearance after sphincterotomy. Of 283 patients with choledocholithiasis referred to their tertiary facility, 85 failed to have their ducts cleared with the first ERCP. There were 21 male and 64 female subjects; mean age was 77.5 yr. Clinical presentations were jaundice (39), cholangitis (23), and biliary colic and/or abnormal liver blood tests in the remainder. The patients were characterized as "elderly and ill with either jaundice or cholangitis present in almost 75%." Follow-up data were obtained for all patients. ERCP was first performed using a duodenoscope with a 3.2-mm instrument channel. A 7-French double pigtail stent was placed in each of the 85 patients with retained stones. Subsequent ERCP were performed at 2- to 3-month intervals using a therapeutic duodenoscope (4.2-mm instrument channel). A second stent was placed if stones remained in the bile duct after repeated extraction attempts. Patients deemed too frail and elderly for frequent ERCP had their first stent left in place, with stent exchanges and attempts at stone extraction every 6-12 months. Mechanical lithotripsy was used in 23 patients, extracorporeal shock wave lithotripsy (ESWL) in 11, and dissolution therapy via nasobiliary catheter in 10. Acute illnesses resolved in 84 of 85 patients, with significant decreases in bilirubin and alkaline phosphatase levels by the second ERCP. Six patients died with temporary stents in situ, one form a respiratory arrest the day of ERCP; the other deaths were unrelated to ERCP or choledocholithiasis. Fifty of the remaining 79 patients had successful stone clearance; 68% of these required two ERCP, 20% three ERCP, 6% four ERCP, and, in another 6%, a total of five ERCP were required before their ducts were free of stones. Seven cases of cholangitis among these 50 patients were treated successfully with i.v. antibiotics, fluids, and "early" stent replacement. Twenty-six patients had long term biliary drainage with the original stents in situ over 12 months. Four of these patients were among the six deaths, all unrelated to biliary stones or ERCP. Three patients were referred for surgical stone removal. The authors conclude that placement of a single 7-French stent after failure to clear common duct stones is safe, provides affective biliary drainage, can prevent the need for urgent surgical intervention, and allows for transfer of sick patients to centers of expertise. Further attempts at bile duct clearance were successful in most cases.


Platelet expression profiling and clinical validation of myeloid-related protein-14 as a novel determinant of cardiovascular events.
Platelets participate in events that immediately precede acute myocardial infarction. Because platelets lack nuclear DNA but retain megakaryocyte-derived mRNAs, the platelet transcriptome provides a novel window on gene expression preceding acute coronary events. We profiled platelet mRNA from patients with acute ST-segment-elevation myocardial infarction (STEMI, n=16) or stable coronary artery disease (n=44). The platelet transcriptomes were analyzed and single-gene models constructed to identify candidate genes with differential expression. We validated 1 candidate gene product by performing a prospective, nested case-control study (n=255 case-control pairs) among apparently healthy women to assess the risk of future cardiovascular events (nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death) associated with baseline plasma levels of the candidate protein. Platelets isolated from STEMI and coronary artery disease patients contained 54 differentially expressed transcripts. The strongest discriminators of STEMI in the microarrays were CD69 (odds ratio 6.2, P<0.001) and myeloid-related protein-14 (MRP-14; odds ratio 3.3, P=0.002). Plasma levels of MRP-8/14 heterodimer were higher in STEMI patients (17.0 versus 8.0 microg/mL, P<0.001). In the validation study, the risk of a first cardiovascular event increased with each increasing quartile of MRP-8/14 (Ptrend<0.001) such that women with the highest levels had a 3.8-fold increase in risk of any vascular event (P<0.001). Risks were independent of standard risk factors and C-reactive protein. The platelet transcriptome reveals quantitative differences between acute and stable coronary artery disease. MRP-14 expression increases before STEMI, and increasing plasma concentrations of MRP-8/14 among healthy individuals predict the risk of future cardiovascular events.


Study on Biomarkers Related to the Treatment of Post-Stroke Depression and Alternative Medical Treatment Methods.
PSD is a syndrome that occurs after a stroke, which manifests as a series of depressive symptoms and corresponding physiological symptoms. Relevant studies have shown that the drug therapy is often accompanied by drug side effects and patient resistance. Acupuncture has attracted attention as a treatment method without adverse reactions of patients. The purpose of this study was to investigate the possible mechanism of action of acupuncture in PSD. Download depression and stroke datasets from public databases. Bioinformatics methods were used to analyze the key gene targets related to stroke and depression. Functional enrichment analysis assesses important pathways. Further screen PSD-related biological pathways and genes. After the experimental model was established, the expression differences of key genes and related pathways were compared between the model group and the control group through acupuncture treatment and qPCR verification. Depression and stroke-related genes were obtained by bioinformatics methods, and then important biological processes and biological pathways related to depression and stroke were analyzed by GO and KEGG. And further screen out the disease targets closely related to PSD. In the follow-up animal experiments, we confirmed that acupuncture can intervene on these key pathways and targets, and then play a role in the targeted therapy of diseases. The results of this study show that five genes ("NRBP1", "SIRT1", "BDNF", "MAPK3", "CREB1".) and key biological pathways such as NFkB, PI3K/AKT activation, and MAPK are the keys to the occurrence and development of PSD biomarkers, which can also be therapeutically intervened by acupuncture.


Use of Expert Consultation in a Complex Case of Neuroleptic Malignant Syndrome Requiring Electroconvulsive Therapy.
Our team at Emory University Hospital contacted experts at the National Network of Depression Centers (NNDC) for clinical guidance concerning a patient with schizophrenia hospitalized in the intensive care unit with a complex case of prolonged delirium secondary to neuroleptic malignant syndrome (NMS). Through the NNDC, leading psychiatrists across the United States with expertise in electroconvulsive therapy (ECT) provided us with treatment strategies based on experience in our area of concern. This report describes our use of ECT to treat severe NMS in this patient with schizophrenia, utilizing the recommendations made by the NNDC's ECT experts concerning electrode position, number and frequency of treatments, and selection of anesthetic induction agents. This case report highlights the utility of expert consultation in the treatment of rare diseases and provides guidance on how to treat NMS in the intensive care unit setting.


Molecular Pathogenesis, Immunopathogenesis and Novel Therapeutic Strategy Against COVID-19.
The coronavirus disease 2019 (COVID-19), is a highly contagious transmittable disease caused by a recently discovered coronavirus, pathogenic SARS-CoV-2. Followed by the emergence of highly pathogenic coronaviruses in 2003 SARS-CoV, in 2012 MERS-CoV, now in 2019 pathogenic SARS-CoV-2, is associated with a global "pandemic" situation. In humans, the effects of these viruses are correlated with viral pneumonia, severe respiratory tract infections. It is believed that interaction between angiotensin converting enzyme 2 (ACE2) cell receptor and viral Spike protein mediates the coronavirus entry into human respiratory epithelial cells and establishes the host tropism. ACE2 receptor is highly expressed in airway epithelial cells. Along with viral-receptor interaction, proteolytic cleavability of S protein has been considered as the determinant of disease severity. Several studies highlight the occurrence of impaired host immune response and expression of excessive inflammatory response especially cytokines against viral infection. The mechanisms of SARS-CoV-2 induced acute lung injury are still undefined; however, the term cytokine storm has now been recognized to be closely associated with COVID-19. The levels of inflammatory mediators from cytokine storm cause damage to the host cells. In particular, the proinflammatory cytokine IL-6 appears to be the key mediator in early phase of virus-receptor interaction; however, secreted IL-6 might not be representative of lung inflammation. Understanding the cellular, and molecular factors involved in immune dysregulation and the high virulence capacity of COVID-19 will help in potential targeted therapy against it. "Drug repurposing" and "molecular docking analysis" is considered as an attractive alternative approach in analyzing suitable drug candidates to combat SARS-CoV-2 infection. Globally, extensive research is in progress to discover a new vaccine for novel COVID-19. Moreover, our review mainly focuses on the most state-of-the-art therapeutic approach mediated by "Mannose-binding lectin (MBL)." One of the most significant molecules of innate immunity is MBL. It plays a major role in the activation of the complement system as an ante-antibody prior to the response of any particular antibody. Recombinant human MBL can be used as immunomodulators against SARS-CoV-2.


Characterization of melanocortin NDP-MSH agonist peptide fragments at the mouse central and peripheral melanocortin receptors.
The central melanocortin receptors, melanocortin-4 (MC4R) and melanocortin-3 (MC3R), are involved in the regulation of satiety and energy homeostasis. The MC4R in particular has become a pharmaceutical industry drug target due to its direct involvement in the regulation of food intake and its potential therapeutic application for the treatment of obesity-related diseases. The melanocortin receptors are stimulated by the native ligand, alpha-melanocyte stimulating hormone (alpha-MSH). The potent and enzymatically stable analogue NDP-MSH (Ac-Ser-Tyr-Ser-Nle-Glu-His-DPhe-Arg-Trp-Gly-Lys-Pro-Val-NH(2)) is a lead peptide for the identification of melanocortin amino acids important for receptor molecular recognition and stimulation. We have synthesized nine peptide fragments of NDP-MSH, deleting N- and C-terminal amino acids to determine the "minimally active" sequence of NDP-MSH. Additionally, five peptides were synthesized to study stereochemical inversion at the Phe 7 and Trp 9 positions in attempts to increase tetra- and tripeptide potencies. These peptide analogues were pharmacologically characterized at the mouse melanocortin MC1, MC3, MC4, and MC5 receptors. This study has identified the Ac-His-DPhe-Arg-Trp-NH(2) tetrapeptide as possessing 10 nM agonist activity at the brain MC4R. The tripeptide Ac-DPhe-Arg-Trp-NH(2) possessed micromolar agonist activities at the MC1R, MC4R, and MC5R but only slight stimulatory activity was observed at the MC3R (at up to 100 microM concentration). This study has also examined to importance of both N- and C-terminal NDP-MSH amino acids at the different melanocortin receptors, providing information for drug design and identification of putative ligand-receptor interactions.


Annual universal influenza vaccination: ready or not?
Influenza causes annual worldwide epidemics of respiratory disease. Currently, the United States and many other countries recommend influenza vaccination for persons who are at high risk for influenza-related complications. This commentary explores the potential benefits of a policy advocating universal annual influenza vaccination and outlines obstacles that need to be overcome to make such a recommendation feasible. The 5-year experience of a free influenza vaccination program for everyone > or =6 months of age in the Canadian province of Ontario is reviewed.


Familial infantile convulsions and paroxysmal choreoathetosis: a new neurological syndrome linked to the pericentromeric region of human chromosome 16.
Benign infantile familial convulsions is an autosomal dominant disorder characterized by nonfebrile seizures, with the first attack occurring at age 3-12 mo. It is one of the rare forms of epilepsy that are inherited as monogenic Mendelian traits, thus providing a powerful tool for mapping genes involved in epileptic syndromes. Paroxysmal choreoathetosis is an involuntary-movement disorder characterized by attacks that occur spontaneously or are induced by a variety of stimuli. Classification is still elusive, and the epileptic nature of this movement disorder has long been discussed and remains controversial. We have studied four families from northwestern France in which benign infantile convulsions was inherited as an autosomal dominant trait together with variably expressed paroxysmal choreoathetosis. The human genome was screened with microsatellite markers regularly spaced, and strong evidence of linkage for the disease gene was obtained in the pericentromeric region of chromosome 16, with a maximum two-point LOD score, for D16S3133, of 6.76 at a recombination fraction of 0. Critical recombinants narrowed the region of interest to a 10-cM interval around the centromere. Our study provides the first genetic evidence for a common basis of convulsive and choreoathetotic disorders and will help in the understanding and classification of paroxysmal neurological syndromes.


Advances in thoracoscopy: 100 years since Jacobaeus.
Thoracoscopy provides the physician a window into the pleural space, and enables the biopsy of the parietal pleura under direct visual guidance, chest tube placement and pleurodesis for recurrent pleural effusions or pneumothoraces in selected patients. In this review, we discuss the advances that have been achieved in thoracoscopy since its inception more than a century ago.


Infrared spectra and photochemistry of matrix-isolated pyrrole-2-carbaldehyde.
Monomeric pyrrole-2-carbaldehyde (P2C) was isolated in low-temperature argon and xenon matrices, and its UV-induced photochemistry was studied. The structures of the reagent as well as the reaction photoproducts were characterized by FTIR spectroscopy. Interpretation of the experimental results was assisted by theoretical calculations carried out at the MP2 and DFT (B3LYP) levels with the 6-311++G(d,p) basis set. The compound can assume two conformations, cis and trans, regarding the orientation of the N-C-C=O dihedral angle. The cis form is the conformational ground state, being more stable than the trans by ca. 15 kJ mol(-1). The relative stability of the two conformers was analyzed based on the comparison of their structures and using the natural bond orbital method. In agreement with the calculations, only the signature of the cis conformer was found in the experimental FTIR spectra of matrix-isolated P2C monomers. UV irradiation (lambda > 235 nm) readily converts the cis-P2C into the trans-P2C form, and a photostationary equilibrium is established where the [cis]/[trans] ratio is ca. 3.3:1 in both Ar and Xe. Upon prolonged irradiation, P2C slowly undergoes photolysis to [pyrrole + CO]. In matrices, pyrrole and CO form associates of different geometry, which could be characterized based on their vibrational signatures.


Award for Distinguished Scientific Early Career Contributions to Psychology: Daisy R. Singla.
The Early Career Awards, given for the first time in 1974, recognize the large number of excellent early career psychologists. Recipients of this award may not have held a doctoral degree for more than nine years. For purposes of this award, psychology has been divided into 10 areas: animal learning and behavior, comparative; developmental; health; cognition/human learning; psychopathology; behavioral and cognitive neuroscience; perception/motor performance; social; applied research; and individual differences. Five areas are considered each year, with areas rotated in two-year cycles. The areas considered in 2021 were animal learning and behavior, comparative; developmental; health; cognition/human learning; and psychopathology. Each year, panels are selected for the areas under consideration, and these panels recommend nominees to the Committee on Scientific Awards. The 2021 recipients of the APA Scientific Contribution Awards were recognized by the 2020 Board of Scientific Affairs and selected by the 2020 Committee on Scientific Awards. For innovative research in the area of global mental health with an emphasis on improving access to evidence-based psychological therapies to historically under-served populations. Daisy R. Singla has emerged as a leader in the strategy of task-sharing of interventions to non-specialist providers, and her work spans the design of culturally adapted interventions, the assessment of competencies, and the implementation of measurement-based peer supervision, in the context of large pragmatic clinical trials in real-world settings in three continents. Her work also incorporates rigorous tests of moderation and mediation in the process of reducing inequities in access to evidence-based mental health care. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


COVID Stress, socioeconomic deprivation, and intimate partner aggression during the COVID-19 pandemic.
Intimate partner aggression (IPA) is a prevalent public health concern that is associated with multiple negative consequences. Rates of IPA in the U.S. have increased since the onset of the Coronavirus Disease 2019 (COVID-19) pandemic, likely due to stress associated with the pandemic. Socioeconomic deprivation is associated with COVID-19 outcomes as well as IPA. However, whether socioeconomic deprivation interacts with COVID-19 stress in predicting IPA remains unclear. Using a sample of 510 individuals recruited via Qualtrics Research Services in April 2020, the present study tested whether socioeconomic deprivation moderates the association between COVID-19 stress and IPA perpetration and victimization. Participants completed a questionnaire battery that included measures of COVID-19 stressors and physical and psychological IPA perpetration and victimization. In addition, participants reported their residential zip codes, which were subsequently matched with scores on the Social Deprivation Index, a composite measure of seven demographic variables from the 5-year American Community Survey. Sequential generalized linear models in Mplus Version 8.7 showed that the effects of COVID-19 stress on physical IPA perpetration and psychological IPA victimization can be best understood through its interactive effects with socioeconomic deprivation. Higher COVID-19 stress was associated with higher levels of physical IPA perpetration and psychological IPA victimization when socioeconomic deprivation was low but not when socioeconomic deprivation was high. Importantly, however, overall rates of IPA were higher among individuals with higher socioeconomic deprivation than among individuals with lower socioeconomic deprivation, regardless of the amount of COVID-19 stress they experienced. The present analyses implicate COVID-19 stress as a critical correlate of IPA and show that the association between this stress and physical IPA perpetration and psychological IPA victimization may be particularly salient among individuals who live in areas of lower socioeconomic deprivation. Furthermore, our results clearly pinpoint the detrimental effects of socioeconomic deprivation more broadly, showing that individuals who live in more deprived areas tend to have high levels of IPA regardless of their level of COVID-19 stress. These findings call for public health policies at the community and societal level that target not only COVID-related stress but also the impacts of socioeconomic inequality.


An assessment of blast modelling techniques for injury biomechanics research.
Blast-induced traumatic brain injury (TBI) has been affecting combatants and civilians. The blast pressure wave is thought to have a significant contribution to blast-related TBI. Due to the limitations and difficulties of conducting blast tests on surrogates, computational modelling has been used as a key method for exploring this field. However, the blast wave modelling methods reported in current literature have drawbacks. They either cannot generate the desirable blast pressure wave history or they are unable to accurately simulate the blast wave/structure interaction. In addition, boundary conditions, which can have significant effects on model predictions, have not been described adequately. Here, we critically assess the commonly used methods for simulating blast wave propagation in air (open-field blast) and its interaction with the human body. We investigate the predicted blast wave time history, blast wave transmission, and the effects of various boundary conditions in three-dimensional (3D) models of blast prediction. We propose a suitable meshing topology, which enables accurate prediction of blast wave propagation and interaction with the human head and significantly decreases the computational cost in 3D simulations. Finally, we predict strain and strain rate in the human brain during blast wave exposure and show the influence of the blast wave modelling methods on the brain response. The findings presented here can serve as guidelines for accurately modelling blast wave generation and interaction with the human body for injury biomechanics studies and design of prevention systems.


Comprehensive proteomic profiling of plasma-derived Extracellular Vesicles from dementia with Lewy Bodies patients.
Proteins and nucleic acids contained in extracellular vesicles (EVs) are considered a feasible source of putative biomarkers for physiological and pathological conditions. Within the nervous system, not only neurons but also other brain cells are able to produce EVs, which have been involved in their physiological processes and also in the development and course of several neurodegenerative diseases. Among these, dementia with Lewy bodies (DLB) is the second cause of dementia worldwide, though most cases are missed or misdiagnosed as Alzheimer's disease (AD) due to the important clinical and pathological overlap between both diseases. In an attempt to find reliable biomarkers for DLB diagnosis, our group characterized the proteome of plasma-derived EVs from DLB patients compared to aged-matched healthy controls (HCs) using two different proteomic LC-MS/MS approaches. Remarkably, we found that gelsolin and butyrylcholinesterase were differentially identified between DLB and HCs. Further validation of these results using conventional ELISA techniques, and including an additional group of AD patients, pointed to decreased levels of gelsolin in plasma-EVs from DLB compared to HCs and to AD samples. Thus, gelsolin may be considered a possible biomarker for the differentiation between DLB and AD.


IgE-mediated hypersensitivity reaction to lignocaine - a case report.
We report a 7 year old girl who developed ipsilateral left facial swelling immediately after lignocaine injection. Skin prick test showed positive reaction to pure 2% lignocaine hydrochloride and to lignocaine oral dental gel. Specific Immunoglobulin E (Ig E) to lignocaine was detected. Lignocaine is a commonly used anaesthetic agent mainly as local anaesthesia. However type I hypersensitivity to lignocaine is rare and there have been very few cases reported in the literature.


Nanopore formation on unilamellar vesicles of long- and short-chain lipids.
The structure of unilamellar vesicles (ULVs), comprising long- and short-chain lipids, was investigated, and the formation of nanopores on the surface of the ULVs was confirmed under the condition of long- and short-chain lipids being separated. It was also revealed that the behavior of the structural phase transition from ULVs to bilayered micelles (bicelles) depends on the number of nanopores formed on the surface of the ULVs. Because both the rim structures of nanopores and bicelles are considered to be microdomains of short-chain lipids, this phase behavior was explained by considering the kinetic pathway of the growth of the rim domain. It was concluded that the phase segregation of lipids plays an essential role in the rim formation of nanopores as well as bicelles.


The Glycan Structure of T. cruzi mucins Depends on the Host. Insights on the Chameleonic Galactose.
Trypanosoma cruzi, the protozoa that causes Chagas disease in humans, is transmitted by insects from the Reduviidae family. The parasite has developed the ability to change the structure of the surface molecules, depending on the host. Among them, the mucins are the most abundant glycoproteins. Structural studies have focused on the epimastigotes and metacyclic trypomastigotes that colonize the insect, and on the mammal trypomastigotes. The carbohydrate in the mucins fulfills crucial functions, the most important of which being the accepting of sialic acid from the host, a process catalyzed by the unique parasite trans-sialidase. The sialylation of the parasite influences the immune response on infection. The O-linked sugars have characteristics that differentiate them from human mucins. One of them is the linkage to the polypeptide chain by the hexosamine, GlcNAc, instead of GalNAc. The main monosaccharide in the mucins oligosaccharides is galactose, and this may be present in three configurations. Whereas β-d-galactopyranose (β-Galp) was found in the insect and the human stages of Trypanosoma cruzi, β-d-galactofuranose (β-Galf) is present only in the mucins of some strains of epimastigotes and α-d-galactopyranose (α-Galp) characterizes the mucins of the bloodstream trypomastigotes. The two last configurations confer high antigenic properties. In this review we discuss the different structures found and we pose the questions that still need investigation on the exchange of the configurations of galactose.


Sexual dysfunction in men and women on peritoneal dialysis: Differential link with metabolic factors and quality of life perception.
Sexual function, psychosocial status and quality of life (QoL) are important dimensions, often underestimated, in dialysis treatment schedules. The aim of this study was to evaluate the prevalence of sexual dysfunction and its associations, among peritoneal dialysis (PD) patients. The Index of Female Sexual Function (IFSF), the International Index of Erectile Function (IIEF), the Hospital Anxiety and Depression Scale (HADS) and the Quality of Life EQ5D questionnaires were applied to a prevalent PD population of 57 enrolled patients. Multivariate analysis was conducted to investigate clinical independent risk factors for sexual dysfunction. Sexual dysfunction was diagnosed in 67.9% of women and 44.8% of men. In females, serum albumin, creatinine and phosphorus levels and EQ5D positively correlated with IFSF score. For males, there was a significant negative correlation between serum calcium levels and the IIEF score. On multivariate analysis, nutritional parameters remained independently associated with sexual dysfunction in women; in males, increase in calcium concentration and decrease of testosterone were main determinants. On logistic regression analysis, the risk of sexual dysfunction in global population was associated with lower values of albumin (OR=6.94) and with a lower QoL score EQ5D (OR=6.93). Sexual dysfunction is highly prevalent and strongly associated with impaired QoL of PD patients. Different clinical variables were related to sexual dysfunction in each gender, justifying an individualized preventive and therapeutic approaches.


Transient radicular irritation after spinal anaesthesia with 2% isobaric lignocaine.
A typical case of transient radicular irritation after spinal anaesthesia with 2% isobaric lignocaine is described. The definition and history of this syndrome and the implications of the use of pencil point needles with lignocaine for spinal anaesthesia are discussed.


Effect of pulmonary blood flow upon lung mechanics.
Airway pressure was continuously recorded in an isolated horizontally mounted canine heart-lung preparation during abrupt, stepwise 100-200 ml inflations to 20-25 cm water pressure, and subsequent deflations. With each change in volume there was a steep rise or fall in pressure, followed by stress relaxation to a static equilibrium airway pressure. Comparison was made between the nonperfused state and during perfusion with whole blood at 100 ml/kg dog wt per min, and left atrial pressure of 10 mm Hg. Pressure tracings were similar during deflation in the perfused and the nonperfused lung. During inflation, in the middle range of lung inflation volumes, the peak inflation and equilibrium airway pressures were greater in the nonperfused state; maximum difference of static pressures in nine preparations averaged 146% of perfused values and the average stress relaxation difference from eight of these was 276%. Lung distensibility was the same with packed red cells or plasma perfusates and was not changed by varying the perfusion rate up to 220 ml/kg per min. During cyclic ventilation, dynamic compliance was similarly greater in the perfused than in the nonperfused state in the middle range of inflation volumes. Static distention of the vascular bed produced similar results with progressive improvement in distensibility in mid-inflation range up to a hydrostatic pressure of 15 cm blood. These data suggest that the distended pulmonary vascular bed provides structural airway support which facilitates entry of gas into the terminal respiratory units at diminished pressure.


Biosynthetic Structural Proteins with Super Plasticity, Extraordinary Mechanical Performance, Biodegradability, Biocompatibility and Information Storage Ability.
Degradable bioplastics have attracted growing interest worldwide. However, it is challenging to develop bioplastics with a simple processing procedure, strong mechanical performance, good biocompatibility, and adjustable physicochemical properties. Herein, we introduced structural proteins as building blocks and developed a simple environmentally friendly approach to fabricate diverse protein-based plastics. A cost-effective and high-level production approach was developed through batch fermentation of Escherichia coli to produce the biomaterials. These bioplastics possess super plasticity, biocompatibility, biodegradability, and high resistance to organic solvents. Their structural and mechanical properties can be precisely controlled. Besides, high density information storage and hemostatic applications were realized in the bioplastic system. The customizable bioplastics have great potential for applications in numerous fields and are capable to scale up to the industrial level.


Carboxyl-terminal targeting and novel post-translational processing of JAW1, a lymphoid protein of the endoplasmic reticulum.
Jaw1 is a lymphoid-restricted protein localized to the cytoplasmic face of the endoplasmic reticulum (ER) and is a member of a recently recognized class of integral membrane proteins that contain carboxyl-terminal membrane anchors. The carboxyl-terminal 71 amino acids of the Jaw1 protein, which contain a hydrophobic membrane spanning region, are sufficient to target a heterologous protein to the ER. By discontinuous sucrose gradient ultracentrifugation, differential sedimentation was noted for the four major Jaw1 protein isoforms, with two of the forms predominantly soluble and two microsome-bound. Pulse-chase immunoprecipitations suggest a post-translational modification of two major isoforms of the protein resulting in an increase in mobility on SDS-polyacrylamide gel electrophoresis. In vitro translation studies are compatible with a post-translational processing event that results in cleavage of a short 36 amino acid lumenal domain. These findings define a carboxyl-terminal domain of the Jaw1 protein that is both necessary and sufficient for ER localization. In addition, the processing of the small lumenal domain of Jaw1 represents a novel post-translational protein modification performed by the endoplasmic reticulum.


Sphingomyelinase and ceramide suppress insulin-induced tyrosine phosphorylation of the insulin receptor substrate-1.
The sphingomyelin pathway is a newly described signal transduction pathway mediating the action of several cytokines including tumor necrosis factor-alpha (TNF). TNF was recently shown to interfere with insulin-induced tyrosine phosphorylation of the insulin receptor substrate-1 (IRS-1). In this work we examined the possible effect of direct activation of the sphingomyelin pathway on insulin-induced tyrosine phosphorylation of IRS-1. Incubation of the insulin-sensitive rat hepatoma Fao cells with bacterial sphingomyelinase (SMase) that causes membrane hydrolysis of sphingomyelin led to a time- and dose-dependent decrease in insulin-induced tyrosine phosphorylation of IRS-1. The effect was apparent after 10 min of incubation and with a dose of 10 milliunits/ml SMase. It was not associated with a decrease in insulin receptor autophosphorylation. In addition, SMase treatment interrupted the association of the 85-kDa catalytic subunit of phosphatidylinositol 3-kinase with IRS-1. A similar impact on IRS-1 tyrosine phosphorylation was observed after addition of cell-permeable ceramide analogs (C2 and C6). Comparable changes in IRS-1 tyrosine phosphorylation and electrophoretic mobility were found after exposure of cells to either TNF, SMase, or ceramide. Our findings suggest that TNF may utilize the sphingomyelin pathway in its effect on the insulin-stimulated tyrosine phosphorylation of IRS-1.


[Isolation of mouse primary hepatocytes by retrograde liver perfusion with catheterization via heart].
To explore the effects of retrograde liver perfusion with catheterization via heart on the isolation of primary mouse hepatocytes. In order to more efficiently isolate primary mouse hepatocytes, we improved the traditional two-step collagenase perfusion method. The liver perfusion catheter was inserted through right atrium and suprahepatic vena cava, and the perfusion velocity was controlled by the drip infusion with collagenase perfusate containing 10% of fetal calf serum. Total success rate of catheterization in the improved group was as high as 95%, and the success rate of first at ttempt in the improved group was significantly higher than that in the traditional group (94.7% vs. 68.8%). Liver perfusion in the improved group was symmetrical with the high yield of hepatocytes up to 1.07 x 10(6) per gram of mouse weight and 92.16% of average cell vitality, which were higher than those in the traditional group. The retrograde liver perfusion through the heart is a simple and easy-to-learn method to isolate mouse primary hepatocytes, which also could guarantee the satisfactory yield and vitality of primary hepatocytes.


Case of Olmsted Syndrome with Essential Thrombocytosis Misdiagnosed as Acrodermatitis Enteropathica.
Olmsted syndrome is a rare genodermatosis. Palmoplantar keratoderma and periorificial keratodermic plaques are the most important clinical findings. Additional findings associated with a large number of systems may accompany such as teeth, nail deformities, alopecia, mental retardation, and bone-joint anomalies. Therefore, it is difficult to make a differential diagnosis from other palmoplantar keratodermas. It also needs to be differentiated from acrodermatitis enteropathica because of periorificial plaques. The absence of regression in lesions with zinc treatment excludes this disease. We present here an Olmsted syndrome case with essential thrombocytosis for the first time.


A nickel complex of a conjugated bis-dithiocarbazate Schiff base for the photocatalytic production of hydrogen.
We report a nickel complex containing a conjugated bis-dithiocarbazate ligand that is an active catalyst for the reduction of protons into hydrogen gas. Light-driven hydrogen generation is observed from a system containing this molecular nickel catalyst coupled with a fluorescein photosensitizer and triethylamine sacrificial donor. The photocatalytic system is stable for over 70 hours, achieving 3300 turnovers with respect to catalyst. The complex is also an active electrocatalyst for proton reduction with catalysis occurring at -1.7 V vs. Fc(+)/Fc. The nickel bis-dithiocarbazate complex represents a highly active and stable catalyst for hydrogen generation.


In vitro studies on the antioxidant and protective effect of 2-substituted -8-hydroxyquinoline derivatives against H(2)O(2)-induced oxidative stress in BMSCs.
Novel 2-vinyl-8-hydroxyquinoline derivatives as potential antioxidants and regulators of H(2)O(2)-induced oxidative stress in rat bone marrow mesenchymal stem cells (MSCs) are first reported. The antiradical properties and the reducing power of these compounds were assessed using 2, 2-diphenyl-1-picrylhydrazyl (DPPH) and auto-oxidation of pyrogallol method, respectively. The activity against lipid peroxidation was determined using ammonium thiocyanate method. The results revealed that introduction of electron-donating groups at 2nd position decreased the antioxidant activities of 8-hydroxyquinoline derivatives. In addition, compound 4, the structure of which is similar to melatonin, exhibited superior antioxidant activities in scavenging DPPH free radical, O(2) free radical, and anti-LPO activities. Except for compounds 7, 12, and 15, the other compounds exhibited a stimulatory effect on MSCs growth. Using hydrogen peroxide (H(2)O(2)), we also investigated the protective efficacy of 2-vinyl-8-hydroxyquinoline derivatives against oxidative stress-induced cell death of MSCs. Cell viability assayed by MTT method indicated that exposure of MSCs cultures to hydrogen peroxide resulted in a concentration-dependent decrease in cell viability, and compounds 4 and 5 at given concentration (2.62 x 10(-3) m) could protect MSCs against H(2)O(2)-induced oxidative stress in bone mesenchymal stem cell (BMSCs).


Aurora A kinase activates YAP signaling in triple-negative breast cancer.
The Yes-associated protein (YAP) is an effector that transduces the output of the Hippo pathway to transcriptional modulation. Considering the role of YAP in cancers, this protein has emerged as a key node in malignancy development. In this study, we determined that Aurora A kinase acts as a positive regulator for YAP-mediated transcriptional machinery. Specifically, YAP associates with Aurora A predominantly in the nucleus. Activation of Aurora A can impinge on YAP activity through direct phosphorylation. Moreover, aberrant expression of YAP and Aurora A signaling is highly correlated with triple-negative breast cancer (TNBC). We herein provide evidence to establish the functional relevance of this newly discovered regulatory axis in TNBC.


Rupture of rectal varices treated with endoscopic variceal ligation.
We report here 3 cases of rectal varices treated with endoscopic variceal ligation and discuss the pathogenesis, treatment, and prognosis of rectal varices with referring to previous reports. Of the 3 patients, 2 had been diagnosed as liver cirrhosis and 1 as extrahepatic portal hypertension. All of the 3 patients had previously undergone treatment of esophagogastric varices. The rupture of rectal varices appeared to have some relationship with the treatment of esophageal varices. In previous reports, 73% of patients with ruptured rectal varices treated with endoscopic injection sclerotherapy or endoscopic variceal ligation had undergone treatments of esophageal varices. The endoscopic treatments resulted in a favorable prognosis in 2 patients. Although no fatality from endoscopic injection sclerotherapy or endoscopic variceal ligation has been reported, 1 of the present 3 cases died of liver failure.