Fish oil diets alter the phospholipid balance, fatty acid composition, and steroid hormone concentrations in testes of adult pigs.
The objective was to determine the effect of long-term dietary supplementation of two types of fish oil on lipid composition and steroidogenesis in adult pig testis. Twenty-four Duroc boars, aged 204.5 ± 9.4 d (body weight 128.1 ± 16.7 kg) received daily 2.5 kg of an iso-caloric basal diet supplemented with: 1) 62 g of hydrogenated animal fat (AF); 2) 60 g of menhaden oil (MO) containing 16% of eicosapentaenoic acid (EPA) and 18% of docosahexaenoic acid (DHA); or 3) 60 g of tuna oil (TO) containing 7% of EPA and 33% of DHA. After these diets were consumed for 7 mo, testicular hormones, phospholipid content, and fatty acid composition of individual phospholipids in testis were determined. Body and reproductive organ weights were not significantly affected by dietary treatments. Testicular tissue from boars fed a TO diet, followed by those receiving MO and AF diets, had the lowest level of phosphatidylethanolamine (TO < MO < AF; P < 0.01) but the highest sphingomyelin (TO > MO > AF; P < 0.01). For each phospholipid, boars fed either the MO or TO diet had increased total omega-3 fatty acids, particularly DHA (P < 0.01), by reciprocal replacement of total omega-6 fatty acids (20:4n-6, 22:5n-6). The MO diet increased EPA more than the other diets. Testicular concentrations of testosterone and estradiol were lower in boars fed a TO diet than a MO diet (P < 0.02). In conclusion, long-term dietary supplementation of fish oil, regardless of the EPA/DHA ratio, modified the fatty acid compositions in testis and affected steroid production of healthy adult boars, which may represent a promising models for future studies on fertility.


Case report of aggressive treatments for large-cell neuroendocrine carcinoma of the esophagus.
Neuroendocrine carcinoma of the esophagus is a rare and highly aggressive disease, and the biological features are poorly understood. We report a case of large-cell neuroendocrine carcinoma of the esophagus in a 73-year-old male patient with aggressive surgical treatment. Upper gastrointestinal endoscopy revealed an esophageal large mass. Histological examination of biopsy specimens indicated a neuroendocrine carcinoma. First, we performed subtotal esophagectomy with lymphadenectomy, but he experienced metastasis at the liver and rib 5 months later. Next, we performed partial hepatectomy and radiotherapy for rib metastasis, but he experienced metastasis at the left pulmonary hilar lymph node and sacral bone. Finally, we performed chemotherapy using cisplatin and irinotecan. The therapeutic strategy for large-cell NEC of the esophagus is unestablished. Thus, accumulating the therapeutic results garnered from various treatment tools is considerably important. Aggressive multimodal treatments including surgery have a possibility to gain better survival in patients with large-cell NEC of the esophagus.


Risk factors for retinopathy of prematurity in a district in South India: A prospective cohort study.
The purpose of this study was to determine the incidence, severity, and associated risk factors of retinopathy of prematurity (ROP) in a district in South India. This was a prospective, observational, cohort study involving babies at risk of ROP conducted in five Neonatal Intensive Care Units in a district in Tamil Nadu, South India. All babies with gestational age at birth of ≤36 weeks and a birth weight (BW) of ≤1900 g with a follow-up period of at least 6 months were enrolled for the study. Neonatal and maternal risk factors were assessed and univariate and multivariate logistic regression analysis performed to examine the predictors of ROP. A total of 325 infants were screened. ROP was identified in 210 eyes of 106 (32.6%) babies with severe ROP (stage ≥3 ROP) occurring in 14 (13.2%) babies. Low BW (LBW) was the only significant risk factor for ROP on multivariate logistic regression analysis. The mean BW was 1285 and 1452 g for babies with and without ROP, respectively. Treatment was indicated in 22 eyes of 14 (13.2%) infants. The incidence of ROP was fairly high and strongly associated with LBW. A relatively low incidence of severe ROP was, however, observed. More effort is, therefore, required towards the prevention of preterm births while the present gains in neonatal care should be sustained to reduce the incidence of ROP and thus childhood blindness in the country.


Idiopathic retinal dialysis.
Idiopathic retinal dialyses accounted for 1.8% of 1,789 eyes with rhegmatogenous retinal detachments diagnosed in two institutions over the 6-year period from 1972 through 1977. These detachments characteristically occur in the inferotemporal quadrant of young adult eyes and often are associated with demarcation lines, retinal cysts, peripheral microcystoid degeneration, and yellow-white vitreous opacities. This study provides additional evidence that a distinct type of retinal detachment secondary to nontraumatic retinal dialyses exists. The authors believe that these dialyses probably are secondary to a developmental abnormality of the inferotemporal periphery of the retina and vitreous base. Trauma may precipitate these dialyses but is not the primary cause.


Two Dyscalculia Subtypes With Similar, Low Comorbidity Profiles: A Mixture Model Analysis.
Several studies have aimed to identify subtypes of dyscalculia. In many of these studies, either pre-defined groups (e.g., children with reading and mathematical difficulties vs. children with isolated mathematical difficulties) were analyzed regarding their cognitive profiles (top-down approach), or clusters of children with dyscalculia (CwD) were identified based on a narrow range of cognitive and mathematical skills (data-driven or bottom-up approach). However, it has remained difficult to establish robust subtypes of dyscalculia across studies. Against this background, we conducted a mixture model analysis in order to explore and identify subtypes of dyscalculia based on a broad range of variables (intelligence, reading fluency, working memory, attention, and various mathematical skills). The total sample comprised 174 elementary school CwD (IQ > 70; mathematical abilities: percentile rank <10), which consisted of two subsamples. The first subsample was based on a diagnostic test focusing on calculation (HRT 1-4; n = 71; 46 girls, 25 boys; age: M = 9.28 years, SD = 0.94) whereas the second subsample was based on a diagnostic test with a strong focus on basic numerical capacities (ZAREKI-R; n = 103; 78 girls, 25 boys; age: M = 8.94 years, SD = 1.05). Results provided convincing evidence for the existence of two subtypes in CwD: A slightly impaired subtype and a strongly impaired subtype. Subtypes differed most strongly regarding mathematical abilities, but the analyses suggest that differences in attention could also be a key factor. Therefore, comorbid attention difficulties seem to be a relevant factor that needs to be considered when establishing subtypes. Substantial intelligence differences between dyscalculia subtypes could not be found. Differences in working memory and reading fluency were negligible. Overall, the results seemed to be robust regardless of the diagnostic test used for assessing dyscalculia. When planning interventions for CwD, the existence of a subtype with substantial attention problems should be kept in mind.


Trends Following Implementation of an Otolaryngology Hospitalist Model in a Tertiary Care Setting.
The otolaryngology hospitalist (OH) model is an emerging paradigm for inpatient and acute patient care. This study presents encounter volume before and after the implementation of an OH service. Postimplementation trends are evaluated. Retrospective administrative and clinical database review. Tertiary care university hospital. This review includes 2 distinct time frames (2008-2012, 2014-2018), representing periods before and after OH implementation. The number of billed patient encounters is compared between these 2 periods using the hospital data warehouse. Additional data is evaluated for the postimplementation period, using a clinical database. Encounter type, the reason for consultation, procedures, and requesting service/location are described. After the OH implementation, there was a 451% increase in evaluation and management encounters submitted for billing. Since the OH model inception, there was an overall increase in encounters (849-910), procedures performed (319-345), and operative cases (46-54) per year. Each inpatient consultation request generates one or more procedures on average. Common reasons for consultation include sinonasal pathology (20.3%), dysphonia/dysphagia (17.5%), and airway evaluation (15%). Critical Care (24%), Emergency Medicine (21%), and Hospital Medicine (21%) requested most of the Otolaryngology consults. Most consults were seen on the inpatient medical/surgical floor (46%), with the ICU (27%) and the Emergency Department (22%) being the next most common locations. The OH model is an evolving paradigm that is viable and offers timely, specialized care for patients in a hospital or acute care setting.


Estimation of blood gas contents from expired air under normal and pathologic conditions.
Methods of estimating arterial-venous O2 content difference, mixed venous CO2 content and tension, and average arterial CO2 content are presented. They are based on the continuous gas analysis of expired air during a prolonged expiration. The influence of CO2 storage in lung tissue and certain pathophysiologic conditions on the accuracy of these methods was systematically investigated with a comprehensive multi-chamber computer simulation of the lung. For normal levels of CO2 storage capacity, satisfactory estimates of arterial-venous O2 content difference are feasible for differences less than 8 volumes percent; with high levels of CO2 storage capacity, large errors can occur. Storage of CO2 in lung tissue causes large errors in the estimates of mixed venous CO2 content and tension, and average arterial CO2 content; reliable estimates do not appear to be feasible from analysis of expired gas. Simulated pathophysiologic conditions of interstitial pulmonary edema or atelectasis also introduce large errors. This analysis delineates the theoretic limitations of an estimation technique in clinical applications where acute respiratory dysfunctions occur.


Detection of bovine group B rotaviruses in feces by polymerase chain reaction.
A pair of primers designed from the sequence of genome segment 9 of group B rat rotavirus (IDIR) were employed to amplify genome segment 9 of a group B bovine rotavirus in a polymerase chain reaction (PCR) and to sequence the derived PCR products. A new pair of primers were synthesized from the obtained sequence data and used in a PCR detection assay for group B bovine rotavirus in fecal samples. In addition, another pair of primers were designed to produce a PCR-derived internal probe. This probe was used in a chemiluminescent hybridization to confirm the specificity and to increase the sensitivity of the assay. This assay could detect 0.1 fg of target double-stranded RNA. It was specific to group B bovine rotavirus and did not detect group B rat (IDIR) and porcine rotaviruses, group A bovine (NCDV), simian (SA-11), equine (H-2), porcine (OSU), human (DS-1), deer, and avian rotaviruses, coronavirus, or other enteric organisms tested in this study.


[Carotid artery wall perfusion of the plaque: three dimensional contrast sonographic imaging].
We usually check stenosis rate in patients through the limited directions of angiography. This can result in insufficient evaluation. The importance of the condition of the carotid artery wall in fully accpted nowadays, and ultrasound sonography is being used as a means to study it. Neovascularization in the plaque is one of the pathological factors inducing plaque hemorrhage and rupture, and this is suspected of causing carotid artery stenosis, occlusion and artery-to-artery embolism. Harmonic image is a contrast specific imaging modality, which uses the nonlinear properties of ultrasound contrast agents by transmitting at the fundamental frequency and receiving at multiples of these frequencies. Pulse inversion harmonic image (PIHI), using pulse inversion to eliminate and strengthen the harmonic frequency, is more effective than conventional harmonic imaging. We can detect tissue perfusion by contrast sonographic imaging with PIHI. The routes of vascular wall feeding are as follows: One is diffusion through the endothelium and the other is through the vasa vasorum to the outer part of the medium. So there is no neovascularization at the inner side of the carotid artery. But some plaques have neovascularization in themselves, so we have tried to detect them by the intermittent and real time contrast sonographic imaging method with PIHI. We have already reported the evaluation of neovascularization by the intermittent method and classified from type I to type IV according to the distribution of neovascular vessels in the plaque. The real time contrast sonographic imaging method with PIHI has revealed some characters of neovascularization. Furthermore NV was observed through the real time 3D CAWP by matrix array, though there are some problem for the clinical application.


Peptide inhibitors of appressorium development in Glomerella cingulata.
The phytopathogen Glomerella cingulata (anamorph: Colletotrichum gloeosporioides) infects host tissue by means of a specialised infection structure, the appressorium. The Saccharomyces cerevisiae alpha-mating factor pheromone, the Saccharomyces kluyveri alpha-mating factor pheromone and a hendecapeptide produced by G. cingulata inhibit appressorium development. The amino acid sequence of the G. cingulata peptide, GYFSYPHGNLF, is different from that of the mature pheromone peptides of other filamentous fungi. The peptide has sequence similarity with the Saccharomyces alpha-mating factor pheromones, but is unable to elicit growth arrest in S. cerevisiae.


Extracellular Vesicles and the Promise of Continuous Liquid Biopsies.
The rapid and accurate diagnosis of patients with minimally invasive procedures was once only found in science fiction. However, the discovery of extracellular vesicles (EVs) and their near ubiquity in body fluids, coupled with the advent of inexpensive next generation sequencing techniques and EV purification protocols, promises to make science fiction a reality. Purifying and sequencing the RNA content of EV from routine blood draws and urine samples are likely to enable pathologists and physicians to diagnose and track the progress of diseases in many inaccessible tissues in the near future. Here we present the evolutionary background of EV, summarize the biology of EV formation and cargo selection, and discuss the current barriers to making continuous liquid biopsies through the use of EV a science reality.


Application of a hydrogel sealant improves watertight closures of duraplasty onlay grafts in a canine craniotomy model.
The authors evaluated whether a polyethylene glycol-based hydrogel sealant system improved dural closures with collagen-based duraplasty onlay grafts. Dural defects 1.5 cm in diameter were created in 12 canines and repaired with one of two commercially available duraplasty onlay products. In six animals, hydrogel was applied onto the dural onlays, and the other six animals underwent duraplasty only. Before bone flap replacement, watertight closure was assessed. Before the animals were killed, the craniotomy was reopened, adhesions were rated by a neurosurgeon blinded to the treatment groups, and dural integrity was assessed using pressure testing. The animals that received the hydrogel sealant in addition to the duraplasty withstood intraoperative Valsalva maneuvers up to 20 cm H2O without cerebrospinal fluid (CSF) leakage. The duraplasty-only animals leaked CSF at spontaneous pressures (p = 0.0022). Postoperatively, all six duraplasty-only dogs developed CSF subcutaneous accumulations, compared with only one (16.7%) dog who underwent hydrogel application (p = 0.0152). At the time of harvesting (8 weeks after implantation), duraplasty-only dogs had extensive scarring between the bone flap and the dura mater (median adhesion score 4, range 3-4). The animals receiving hydrogel showed minimal scarring (median adhesion score 0.5, range 0-2). In hydrogel-treated dogs, the mean adhesion score was 82.6% lower than the scores in duraplasty-only animals (p = 0.0043). In animals receiving hydrogel, the mean dural leak pressure was 56.8 +/- 2.5 cm H2O compared with 9.8 +/- 3.8 cm H2O in duraplasty-only dogs (p = 0.0392). Application of the hydrogel was not associated with neurotoxicity, delayed healing, degenerative changes, or increased dura-cortex adhesions. The hydrogel sealant applied to collagen-based dural grafts significantly reduced CSF leakage and functioned as an adhesion barrier. Such technology could be an important tool for cranial surgery.


Stage-specific signals in germ line differentiation: control of Sertoli cell phagocytic activity by spermatogenic cells.
Differentiation of male germ cells requires a continuous cross-talk with their somatic support, the Sertoli cell. An in vitro model of Sertoli cells was recently provided by established cell lines which maintain Sertoli-specific characteristics, among which is a regulated phagocytic capacity. In vivo, Sertoli cells take up the residual cytoplasm expelled from the maturing sperm, a process restricted to a limited period of germinal maturation, and they also eliminate abnormally differentiated germ cells in case of hormonal deficiency. Cells of the Sertoli line efficiently take up latex beads, as well as dead cells in the cultures. A semiquantitative assay of phagocytosis was developed, based on the uptake of fluorescent latex beads. 15P-1 cultures were found to contain a minor fraction of active phagocytes. After addition of a defined fraction of germ cells, however, all the cells internalized beads as efficiently as macrophages. The inducing cell was identified as the pachytene spermatocyte, a cell type which, in vivo, is associated with Sertoli cells when they express their phagocytic potential. These inducing meiotic cells were not internalized themselves. Rather, they interacted with Sertoli cells via a surface signal that was resistant to formaldehyde fixation. The whole induction process does not involve changes in Sertoli gene expression, since it occurs even in the presence of high doses of cycloheximide. After the required initial contact, further maintenance of the activity was dependent on factor(s) secreted in the medium of the activated culture. Phagocytosis was, on the other hand, abrogated in the presence of factor(s) secreted by a distinct fraction of germ cells, enriched in the late stages (second division) of meiosis.


A comparison of the pharmacological actions of 4-aminopyridine and two of its derivatives in the monkey.
The neuromuscular, cardiovascular and central nervous system stimulating effects of 4-aminopyridine (4-AP), 2,4-diaminopyridine (2,4-DAP) and LF-14 were investigated in the monkey. All these compounds were shown to reverse the stable neuromuscular blockade produced by the intravenous infusion of pancuronium bromide. The doses producing 50% antagonism (ED50) of the pancuronium-induced neuromuscular block were 0.50, 0.54 and 0.71 mg/kg for LF-14, 2,4-DAP and 4-AP respectively. The compounds had only slight cardiovascular effects. In contrast to 4-AP, LF-14 and 2,4-DAP did not reduce the duration of ketamine/diazepam-induced anesthesia, suggesting minimal if any central nervous system effects of these two compounds.


New electrohydrodynamic flow caused by the Onsager effect.
We report a new type of electrohydrodynamic (EHD) flow generated around a circular cylinder and a spherical particle in a dielectric liquid under dc and ac electric fields. The EHD flow is observed for various combinations of dielectric liquids and polar additives. We suggest that the EHD flow is caused by a gradient of electrical conductivity produced by a nonuniform electric field and subsequent generation of free charge in the bulk liquid. Analytical and numerical analyses which are based on the leaky-dielectric model show good agreement with experimental results.


An Interrupted Time Series Evaluation of the Testing Makes Us Stronger HIV Campaign for Black Gay and Bisexual Men in the United States.
Black gay, bisexual, and other men who have sex with men (BMSM) are the subpopulation most disproportionately affected by HIV in the United States. Testing Makes Us Stronger (TMUS), a communication campaign designed to increase HIV testing rates among BMSM ages 18 to 44, was implemented in the United States from December 2011 through September 2015. We used interrupted time series analysis (ITSA) to compare pre- and post-campaign trends in monthly HIV testing events among the priority audience in six of the implementation cities from January 2011 through December 2014. In the 11 months prior to the launch of TMUS, HIV testing events among BMSM in the six campaign implementation cities decreased by nearly 35 tests per month (p = .021). After the introduction of TMUS, the number of HIV testing events among BMSM in the same cities increased by more than 6 tests per month (p = .002). ITSA represents a quasi-experimental technique for investigating campaign effects beyond underlying time trends when serial outcome data are available. Future evaluations can be further strengthened by incorporating a comparison group to account for the effects of history and maturation on pre- and post-campaign trends.


Vasculitic emergencies in the intensive care unit: a special focus on cryoglobulinemic vasculitis.
Vasculitis is characterized by the infiltration of vessel walls by inflammatory leukocytes with reactive damage and subsequent loss of vessel integrity. The clinical course of systemic vasculitis may be punctuated by acute life-threatening manifestations that require intensive care unit (ICU) admission. Furthermore, the diagnosis may be established in the ICU after admission for a severe inaugural symptom, mostly acute respiratory failure. Among the systemic vasculitides, cryoglobulinemic vasculitis (CV) has been rarely studied in an ICU setting. Severe CV-related complications may involve the kidneys, lungs, heart, gut, and/or central nervous system. The diagnosis of CV in the ICU may be delayed or completely unrecognized. A high level of suspicion is critical to obtain a timely and accurate diagnosis and to initiate appropriate treatment. We describe severe acute manifestations of CV based on six selected patients admitted to our ICU. That all six patients survived suggests the benefit of prompt ICU admission of patients with severe CV.


Assessment of carotid arterial wall elasticity in type 2 diabetes mellitus patients with microalbuminuria by real-time ultrasound elastography.
The aim of this study was to evaluate carotid arterial wall elasticity in type 2 diabetes mellitus (T2DM) with microalbuminuria by real-time ultrasound elastography. Two hundred and ten T2DM patients were divided into two groups according to levels of urinary albumin excretion (UAE): T2DM without microalbuminuria (T2DM1 group, 120) and T2DM with microalbuminuria (T2DM2 group, 90). The right common carotid arteries were examined by real-time ultrasound elastography. The strain ratio (SR, blood to arterial wall strain ratio) was calculated by dividing the strain value of the blood by that of the carotid arterial wall. The correlation between SR and general data was analyzed. The mean SR value ± SD of T2DM2 group was significantly higher than that of T2DM1 group (P < 0.05). SR was positively and significantly correlated with UAE, HbA1c, and systolic blood pressure (r = 0.456,0.435,0.235, P < 0.05 for all). The mean value ± SD of UAE, HbA1c, 2hPG, BMI, and TC of T2DM2 group was significantly higher than that of T2DM1 group (P < 0.05 for all). In conclusion, there is an association between microalbuminuria and carotid arterial wall elasticity in T2DM patients.


A Process Evaluation of the Isfahan Antibiotic Awareness Campaign: Developing Engagement on Antimicrobial Resistance.
One of the most prominent global health threats is antibiotic resistance, leading to infection treatment failure. The first Iranian antibiotic awareness week campaign was initiated to improve the prudent use and wise prescription of antibiotics. The Isfahan antibiotic awareness campaign was held from November 30 to December 6, 2019, among two targeted populations; the general population and health-care workers by Isfahan University of Medical Sciences. In this campaign held in the main squares, streets, and a city's referral hospital, various educational methods were used to aware and sensitize the general population and medical staff about antibiotics and microbial resistance. These methods include face-to-face training, brochures, advertisement posters and billboards around the city, educational videos, social media messages, retraining for medical doctors and medical specialists, and interviewing in the Islamic Republic of Iran Broadcast. Two hundred and twenty general practitioners, medical specialists, and residents participated in two retraining educational conferences in Al-Zahra Hospital, Isfahan, Iran. The mean score satisfaction of the two conferences was three from four. Nearly 2000 of the general population were under face-to-face educational programs whom after that, 83.6% had the correct answer to the questions around antimicrobial awareness. This campaign was an excellent experience as a pilot study with appealing issues. Further, activities are required to improve engagement with the target population and determine the impact of this campaign on antibiotic consumption and prescription behavior among the public and health-care professionals.


Tracking targeted bimodal nanovaccines: immune responses and routing in cells, tissue, and whole organism.
Dendritic cells (DCs) are the most potent antigen-presenting cells (APCs), involved in the induction of immunity and currently exploited for antitumor immunotherapies. An optimized noninvasive imaging modality capable of determining and quantifying DC-targeted nanoparticle (NP) trajectories could provide valuable information regarding therapeutic vaccine outcome. Here, targeted poly(d,l-lactide-co-glycolide) nanoparticles (PLGA NPs) recognizing DC receptors were equipped with superparamagnetic iron oxide particles (SPIO) or gold nanoparticles with fluorescently labeled antigen. The fluorescent label allowed for rapid analysis and quantification of DC-specific uptake of targeted PLGA NPs in comparison to uptake by other cells. Transmission electron microscopy (TEM) showed that a fraction of the encapsulated antigen reached the lysosomal compartment of DCs, where SPIO and gold were already partially released. However, part of the PLGA NPs localized within the cytoplasm, as confirmed by confocal microscopy. DCs targeted with NPs carrying SPIO or fluorescent antigen were detected within lymph nodes as early as 1 h after injection by magnetic resonance imaging (MRI). Despite the fact that targeting did not markedly affect PLGA NP biodistribution on organism and tissue level, it increased delivery of NPs to DCs residing in peripheral lymph nodes and resulted in enhanced T cell proliferation. In conclusion, two imaging agents within a single carrier allows tracking of targeted PLGA NPs at the subcellular, cellular, and organismal levels, thereby facilitating the rational design of in vivo targeted vaccination strategies.


Impact of a decade of successful antiretroviral therapy initiated at HIV-1 seroconversion on blood and rectal reservoirs.
Persistent reservoirs remain the major obstacles to achieve an HIV-1 cure. Prolonged early antiretroviral therapy (ART) may reduce the extent of reservoirs and allow for virological control after ART discontinuation. We compared HIV-1 reservoirs in a cross-sectional study using polymerase chain reaction-based techniques in blood and tissue of early-treated seroconverters, late-treated patients, ART-naïve seroconverters, and long-term non-progressors (LTNPs) who have spontaneous virological control without treatment. A decade of early ART reduced the total and integrated HIV-1 DNA levels compared with later treatment initiation, but not reaching the low levels found in LTNPs. Total HIV-1 DNA in rectal biopsies did not differ between cohorts. Importantly, lower viral transcription (HIV-1 unspliced RNA) and enhanced immune preservation (CD4/CD8), reminiscent of LTNPs, were found in early compared to late-treated patients. This suggests that early treatment is associated with some immunovirological features of LTNPs that may improve the outcome of future interventions aimed at a functional cure.


TGFβ Pathway Inhibition Redifferentiates Human Pancreatic Islet β Cells Expanded In Vitro.
In-vitro expansion of insulin-producing cells from adult human pancreatic islets could provide an abundant cell source for diabetes therapy. However, proliferation of β-cell-derived (BCD) cells is associated with loss of phenotype and epithelial-mesenchymal transition (EMT). Nevertheless, BCD cells maintain open chromatin structure at β-cell genes, suggesting that they could be readily redifferentiated. The transforming growth factor β (TGFβ) pathway has been implicated in EMT in a range of cell types. Here we show that human islet cell expansion in vitro involves upregulation of the TGFβ pathway. Blocking TGFβ pathway activation using short hairpin RNA (shRNA) against TGFβ Receptor 1 (TGFBR1, ALK5) transcripts inhibits BCD cell proliferation and dedifferentiation. Treatment of expanded BCD cells with ALK5 shRNA results in their redifferentiation, as judged by expression of β-cell genes and decreased cell proliferation. These effects, which are reproducible in cells from multiple human donors, are mediated, at least in part, by AKT-FOXO1 signaling. ALK5 inhibition synergizes with a soluble factor cocktail to promote BCD cell redifferentiation. The combined treatment may offer a therapeutically applicable way for generating an abundant source of functional insulin-producing cells following ex-vivo expansion.


Drug-induced rash: nuisance or threat?
Drug-induced rash is the most commonly reported drug reaction and occurs in a dizzying array of presentations. Changes in lean and fat body tissue, gastrointestinal acid and mucosal permeability, cardiac output, and renal and hepatic metabolism can affect drug absorption, distribution, metabolism, and elimination. Elders may develop cutaneous eruptions from drugs or biologics and be more sensitive to topical medications. Almost all medications have been associated with rash to some degree. Consultant pharmacists should be able to distinguish between the rashes that are uncomfortable from those that are potentially life-threatening. Some drug therapies tend to induce or aggravate "companion" rashes. With select medications, rash is a clinical indicator that the medication is working. Extensive or unusually painful drug-induced skin conditions are rare, but often require fast action by health care providers to direct the patient to life-saving help. Many of these rashes are associated with high mortality, severe complications, and potential chronic disability. Awareness of the drugs that are most likely to cause a rash can help consultant pharmacists work with the clinical team to arrange appropriate care.


Combination therapy for postmenopausal osteoporosis.
A number of agents have been shown to reduce the risk of fractures in patients with postmenopausal osteoporosis. However, the additional benefits of combination therapy as opposed to monotherapy are uncertain. We performed a MEDLINE search and reviewed the published randomized trials of agents used in combination. Combination therapy results in greater gains in bone mineral density than monotherapy and possibly greater effects on bone turnover. However, none of these studies are large enough or of sufficient duration to determine whether a greater reduction in fracture is achieved. Combination therapy has important cost implications and is likely to be associated with an increased prevalence of adverse events, reduced tolerability and a reduction in adherence. Furthermore, over-suppression of bone turnover as a result of combination antiresorptive therapy might have adverse effects on bone strength, particularly with long-term treatment. Thus, the use of combination therapy for treatment of osteoporosis cannot be recommended on the basis of currently available evidence.


Enhancing the Antioxidant Activities of Wines by Addition of White Rose Extract.
White rose petal extract (WRE) contains large amounts of phenolic compounds and is considered edible. In this study, red and white wines were prepared by the addition of WRE (0.10% or 0.25% (w/v)), followed by fermentation at 25°C for 15 days. The fermentation profiles, colors, sensory test results, and antioxidant activities of the wines were compared. As reported herein, the fermentation profiles of the pH, CO₂ production rate, and final ethanol concentration were not affected by the addition of WRE, but a slow consumption rate of sugar was observed in 0.25% WRE-added wine. In contrast, the total polyphenol concentrations in WRE-added wines increased significantly (p < 0.05) in a dose-dependent manner, resulting in appreciable enhancement of the antioxidant activities of the wines. Chromaticity tests showed slight changes in the redness and yellowness, but sensory tests showed that the overall flavor qualities of the WRE-added wines were acceptable to the panels. This study demonstrates that addition of WRE to wine confers beneficial health effects and this treatment results in better outcome in white wine.


Preschool child and adult lateralisation and performance in emotion and language tasks.
A total of 34 undergraduate students from the University of Alabama and 34 preschool children completed measures assessing lateralisation and competency in emotion and language processing in order to examine the developmental time course of the underlying lateralised processes. Results indicate different developmental time courses for lateralisation in dichotic words and chimeric faces tasks, and provide some support for the developmental models of Boles, Barth, and Merrill (2008) concerning the relationship between lateralisation and performance.


Avoiding negative reviewer comments: common statistical errors in anesthesia journals.
Manuscripts submitted to journals should be understandable even to those who are not experts in a particular field. Moreover, they should use publicly available materials and the results should be verifiable and reproducible. Readers and reviewers will want to check the strengths and weaknesses of the research study design, and ways to make this determination should be clear through proper analysis methods. Studies should be described in detail so as to help readers understand the results. Statistical analysis is one of the key methods by which to do this. The inappropriate application of statistical methods could be misleading to readers and clinicians. While many researchers describe their general research methods in detail, statistical methods tend to be described briefly, with certain omissions or errors or other incorrect aspects. For instance, researchers should describe whether the median or mean was used, whether parametric or nonparametric tests were used, whether the data meet the normality test, whether confounding factors were corrected, and whether stratification or matching methods were used. Statistical analysis regardless of the program should be reported correctly. The results may be less reliable if the statistical assumptions before applying the statistical method are not met. These common errors in statistical methods originate from the researcher's lack of knowledge of statistics and/or from the lack of any statistical consultation. The aim of this work is to help researchers know what is important statistically and how to present it in papers.


Update on the Crosstalk Between Adipose Tissue and Mineral Balance in General Population and Chronic Kidney Disease.
Adipose tissue is nowadays considered as a major endocrine organ, which apart from controlling lipid metabolism, displays a significant role in energy expenditure, food intake and in the regulation of various systemic physiological processes. Adipose derived pro-inflammatory cytokines and adipokines, particularly leptin and adiponectin, provide inter-communication of adipose tissue with various metabolic pathways, ultimately resulting in a complex network of interconnected organ systems. Recent clinical and experimental research has been focused on exploring the direct interaction between adipokine profile and elements of mineral metabolism, including parathormone (PTH), fibroblast growth factor-23 (FGF23) and calcitriol. The emerging crosstalk between adipose tissue and calcium and phosphorus homeostasis suggests that metabolic disorders from one system may directly affect the other and vice versa. It is current knowledge that fat metabolism disturbance, commonly encountered in obese individuals, influences the expression of calciotriopic hormones in general population, while various clinical trials attempting to successfully achieve body fat loss by modulating mineral profile have been published. In chronic kidney disease (CKD) state, there is an increasing evidence suggesting that mineral disorders, influence adipose tissue and linked endocrine function. On the contrary, the impact of disturbed fat metabolism on CKD related mineral disorders has been also evocated in clinical studies. Recognizing the pathogenetic mechanisms of communication between adipose tissue and mineral balance is critical for understanding the effects of metabolic perturbations from the one system to the other and for identifying possible therapeutic targets in case of disrupted homeostasis in one of the two connected systems. To that end, this review aims to enlighten the recent advances regarding the interplay between mineral metabolism, fat mass and adipokine profile, based on in vitro, in vivo and clinical studies, in general population and in the course of CKD.


[Application of computer aided design and rapid prototyping technology for defected maxilla restoration].
To test a new cast-making method based on computer aided design (CAD) and rapid prototyping (RP) technology for defected maxilla. Head CT data of 12 patients with defected maxilla were transmitted into a computer. Three-dimensional digital image of the patient's defected maxilla was then obtained based on Mimics 8.11 and Geomagic 7.0 and the plastic cast of the defected region was manufactured by prototyping. The obturator was made on this plastic cast that duplicated the undercut tissue of defected area. The prominent part of the obturator was made of elastic heat-curing resin and it was helpful to gain the retention through the engagement between the obturator and the tissue undercut. After the obturator was finished, the upper removable partial denture was fabricated in conventional method. The combination of these two parts was achieved using magnetic attachment. Clinical effects of obturator and removable partial denture were evaluated and the nasalance value of 5 patients before and after insertion of the obturator was measured using nanometer. The obturator and removable partial denture could be seated into place separately. They all had good retention and stability. After the obturator was seated in place, the nasalance of non-nasal and vowel text decreased from (46.53 +/- 13.86)% to (22.60 +/- 8.52)% (P < 0.001). The cast-making method based on CAD and RP technology for cast-making of defected maxilla is feasible and practical.


Analysis of Fusion Genes by NanoString System: A Role in Lung Cytology?
- Patients with non-small cell lung cancer harboring ALK receptor tyrosine kinase ( ALK), ROS proto-oncogene 1 ( ROS1), and ret proto-oncogene ( RET) gene rearrangements can benefit from specific kinase inhibitors. Detection of fusion genes is critical for determining the best treatment. Assessing rearrangements in non-small cell lung cancer remains challenging, particularly for lung cytology. - To examine the possible application of the multiplex, transcript-based NanoString system (NanoString Technologies, Seattle, Washington) in the evaluation of fusion genes in lung adenocarcinoma samples. - This study is a narrative literature review. Studies about NanoString, gene fusions, and lung adenocarcinoma were collected from PubMed (National Center for Biotechnology Information, Bethesda, Maryland). We found 7 articles about the application of the NanoString system to detect fusion genes on formalin-fixed, paraffin-embedded tumor tissues and one article evaluating the adequacy of lung cytologic specimens for NanoString gene expression analysis. - To maximize the yield of molecular tests on small lung biopsies, the NanoString nCounter system has been suggested to detect fusion genes. NanoString fusion gene assays have been successfully applied on formalin-fixed, paraffin-embedded tissues. Although there are only a few studies available, the application of NanoString assays may also be feasible in lung cytology. According to available data, the NanoString system could strengthen the routine molecular characterization of lung adenocarcinoma.


Analysis of national and single-center incidence and survival after liver transplantation for hepatoblastoma: new trends and future opportunities.
Liver transplantation (LTx) for hepatoblastoma appears to be increasing. Favorable tumor histology is increasingly linked to survival after surgical resection and could also determine posttransplantation outcomes. To evaluate national trends in tumor and LTx incidence as the basis for observations at some LTx centers, and determinants of survival after LTx for hepatoblastoma, we queried the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) registry representing 9.451% of the U.S. population (1975-2007), the United Network for Organ Sharing (UNOS, 1988-2010, n = 332), and Children's Hospital of Pittsburgh database (CHP, 1987-2011, n = 35). In the United States, hepatoblastoma cases increased 4-fold, LTx for hepatoblastoma increased 20-fold, and hepatoblastoma surpassed other unresectable liver malignancies requiring LTx by nearly 3-fold. Actuarial 5-year patient survival exceeded 75%. Recurrences in 16% were greater after segmental LTx in the total U.S. experience (P = .049). At CHP, 5 children died from recurrences (n = 4) and sepsis (n = 1). Tumors were epithelial (57%) or mixed epithelial-stromal (42%), Children's Oncology Group stage III (77%) or IV (23%). Recurrences were related to previous pulmonary metastases (P = .016), and tumor necrosis <50% (P = .013), but not to small cell undifferentiated tumor histology (P = NS). Hepatic artery thrombosis was more common after LTx for hepatoblastoma compared with nonmalignant indications (P = .0089). Thirty-three children received pre-LTx chemotherapy, 88.6% with cisplatin, and 85.7% received post-LTx chemotherapy. Outcomes after LTx for hepatoblastoma may benefit from improved detection and treatment of pretransplantation metastases, adequate tumor lysis after chemotherapy, and perioperative antithrombotic agents but are unaffected by undifferentiated tumor histology.


Improvement of glucose uptake rate and production of target chemicals by overexpressing hexose transporters and transcriptional activator Gcr1 in Saccharomyces cerevisiae.
Metabolic engineering to increase the glucose uptake rate might be beneficial to improve microbial production of various fuels and chemicals. In this study, we enhanced the glucose uptake rate in Saccharomyces cerevisiae by overexpressing hexose transporters (HXTs). Among the 5 tested HXTs (Hxt1, Hxt2, Hxt3, Hxt4, and Hxt7), overexpression of high-affinity transporter Hxt7 was the most effective in increasing the glucose uptake rate, followed by moderate-affinity transporters Hxt2 and Hxt4. Deletion of STD1 and MTH1, encoding corepressors of HXT genes, exerted differential effects on the glucose uptake rate, depending on the culture conditions. In addition, improved cell growth and glucose uptake rates could be achieved by overexpression of GCR1, which led to increased transcription levels of HXT1 and ribosomal protein genes. All genetic modifications enhancing the glucose uptake rate also increased the ethanol production rate in wild-type S. cerevisiae. Furthermore, the growth-promoting effect of GCR1 overexpression was successfully applied to lactic acid production in an engineered lactic acid-producing strain, resulting in a significant improvement of productivity and titers of lactic acid production under acidic fermentation conditions.


High-antibody-producing Chinese hamster ovary cells up-regulate intracellular protein transport and glutathione synthesis.
Chinese hamster ovary (CHO) cells are the preferred production host for therapeutic monoclonal antibodies (mAb) due to their ability to perform post-translational modifications and their successful approval history. The completion of the genome sequence for CHO cells has reignited interest in using quantitative proteomics to identify markers of good production lines. Here we applied two different proteomic techniques, iTRAQ and SWATH, for the identification of expression differences between a high- and low-antibody-producing CHO cell lines derived from the same transfection. More than 2000 proteins were quantified with 70 of them classified as differentially expressed in both techniques. Two biological processes were identified as differentially regulated by both methods: up-regulation of glutathione biosynthesis and down-regulation of DNA replication. Metabolomic analysis confirmed that the high producing cell line displayed higher intracellular levels of glutathione. SWATH further identified up-regulation of actin filament processes and intracellular transport and down regulation of several growth-related processes. These processes may be important for conferring high mAb production and as such are promising candidates for targeted engineering of high-expression cell lines.


Factors associated with fathers' involvement in infant and young child feeding and nurturing care in the urban slums of Bangladesh: A cross-sectional study.
Optimal infant and young child feeding (IYCF) and nurturing care during the first years of children's lives are crucial for ensuring their growth and development. The IYCF and nurturing practices are associated with a multifaceted interplay of context-specific factors where fathers' involvement is necessary. The aim of this study is to explore the current scenario of fathers' involvement in IYCF practices in the urban slums of Bangladesh. A cross-sectional survey among the residents of the Sat Tola slum in Dhaka, the capital of Bangladesh was conducted. To avoid social desirability bias, 361 mothers of children aged <24 months were interviewed regarding fathers' involvement. An operational definition of father's involvement was developed based on 11 criteria and then scoring was applied to classify 'Good Involvement' and associated factors were identified using multivariable logistic regression. Fathers' mean age was around 31 (SD ± 6.09) years and the majority of them (44.32%) completed primary education. Fathers had diversified occupations such as day laborer (32.41%), garment worker (22.71%), and business (14.96%). Factors that were significantly associated with the father's involvement in IYCF practices include educational status (aOR = 3.98, 95% CI = 1.91, 8.26, p < .00) and theiroccupational status (aOR = 0.34, 95% CI = 0.16, 0.70, p = .00). Fathers were more active for their first child (aOR: 1.99, 95% CI = 1.04, 3.79, p = .03). Having child in the age group of 14-20 months (aOR = 2.73, 95% CI = 1.32, 5.64, p = <.01) and wife in the age group of 21-30 years (aOR = 2.34, 95% CI = 1.20, 4.58, p = .01) were significantly associated. The study finding explored that fathers' education and occupation as well as mothers' age and education were significantly associated factors for fathers' involvement in the IYCF practices. Further longitudinal studies are recommended to establish the causal relationship between fathers' involvement with IYCF and their impact on child growth and development.


The patient-centered medical home solution to the cost-quality conundrum.
The U.S. healthcare system has been plagued by rising costs while achieving relatively poor-quality outcomes, and the situation continues to worsen. One solution is the patient-centered medical home (PCMH) model of primary care. This model focuses on care coordination and development of long-term physician-patient relationships that are expected to lead to better quality care and higher rates of patient satisfaction than have previously been achieved. Although the PCMH features a number of core principles, significant differences are seen across models. Three of the most prevalent models are those offered by the American Academy of Family Physicians, National Demonstration Project, and National Committee for Quality Assurance (NCQA). After analysis, the NCQA approach emerged as the recommended model due to its specificity and comprehensiveness. Research suggests that the PCMH, and specifically the NCQA model, can achieve both increases in quality and reductions in cost. However, this finding is tempered by the challenges inherent in implementation.


Differentiation of human myeloid leukemia cell line ML-1 induced by retinoic acid and 1,25-dihydroxyvitamin D3.
Human myeloblastic leukemia cell line ML-1 was induced to differentiate by 1 mumol/l all-trans-retinoic acid (RA) or by 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). After 4-6 days of the induction several differentiation-associated characteristics were observed: (1) Ability to stimulate respiration burst in the ML-1 induced cells as detected by nitroblue tetrazolium (NBT) test or by chemiluminescence (CL). (The percentage of the NBT-positive cells was up to 99% in the RA-induced cells and up to 85% in the 1,25(OH)2D3-induced cells.) (2) Substantially higher phagocytosis of colloid iron, latex or Staphylococcus particles was found in the induced cells. (3) The 1,25(OH)2D3-induced ML-1 cells expressed the monocytic enzyme NaF-inhibitable alpha-naphthyl butyrate esterase and the surface monocytic antigen CD-14. (4) A majority of the induced cells lost the morphological features of blast cells; while the 1,25(OH)2D3-treated cells acquired certain features of monocyte-macrophage differentiation, the RA-treated cells displayed several granulocytic characteristics. (5) Cytofluorometric DNA assay after treatment of the cells with colcemid showed that the decline observed in the growth rate of the induced cells was connected with their arrest in G1/G0 phase of the cell cycle. The obtained results indicate granulocytic differentiation of the RA-induced ML-1 cells and monocyto/macrophage differentiation of the 1,25-(OH)2-D3 induced cells.


Biometric Modeling of Gene-Environment Interplay: The Intersection of Theory and Method and Applications for Social Inequality.
For more than a decade, biometric moderation models have been used to examine whether genetic and environmental influences on individual differences might vary within the population. These quantitative Gene × Environment interaction models have the potential to elucidate not only when genetic and environmental influences on a phenotype might differ, but also why, as they provide an empirical test of several theoretical paradigms that serve as useful heuristics to explain etiology-diathesis-stress, bioecological, differential susceptibility, and social control. In the current article, we review how these developmental theories align with different patterns of findings from statistical models of gene-environment interplay. We then describe the extant empirical evidence, using work by our own research group and others, to lay out genetically informative plausible accounts of how phenotypes related to social inequality-physical health and cognition-might relate to these theoretical models.


[Galectin-1 expression in human colorectal carcinoma and its clinical significance].
To investigate the correlation between galectin-1 expression and the biological behaviors of human colorectal carcinoma. SP immunohistochemistry was used to detect the expression of galectin-1 in 158 paraffin-embedded specimens including 30 normal mucosa, 25 adenoma, 65 colorectal carcinoma and 38 metastatic tumor specimens. Real-time RT-PCR was used to detect galectin-1 mRNA expression in 32 fresh specimens of colorectal carcinoma and normal mucosa. The positive expression level of galectin-1 was significantly different between normal mucosa, adenoma, colorectal carcinomas and metastatic tumors, with positivity rate of 0, 8%, 66% and 86%, respectively (P<0.05). Galectin-1 expression in moderately or well differentiated colorectal carcinomas was significantly lower than that in poorly differentiated ones (P=0.031), and its expression in invasive carcinomas was significantly higher than that in non-invasive carcinomas (P=0.000). Galectin-1 expression in colorectal carcinomas was significantly related with lymph node metastasis (P=0.004). In poorly differentiated colorectal carcinomas, the expression of galectin-1 mRNA was about 2.27 times that in moderately or well differentiated colorectal carcinomas (P=0.00); galectin-1 mRNA expression in invasive carcinoma was 1.98 times that in non-invasive carcinoma (P=0.002). In tumors with lymph node metastasis, galectin-1 mRNA expression was 1.42 times that in tumors without metastasis (P=0.018). Galectin-1 can be involved in the development and progression of colorectal carcinoma, and may relate to the infiltration, differentiation and lymph node metastasis of colorectal carcinoma.


Formation and characterization of microemulsions containing polymeric silicone.
We have prepared microemulsions consisting of water/[40 wt % polyoxyethylene (20 mol) glycerin isostearate (abbreviated as POE-GIS) + 60 wt % random copolymer of polyoxyethylene (POE, 38 mol)/polyoxypropylene (POP, 10 mol) pentaerythritol tetramethyl ether {abbreviated as PEPTME (38/10)}]/[polyoxyethylene (POE, 19 mol)/polyoxypropylene (POP, 19 mol) polydimethylsiloxane copolymer (abbreviated as POE/POP-PDMS)] and water/[40 wt % POE-GIS + 60 wt % PEPTME (38/10)]/[95 wt % POE/POP-PDMS + 5 wt % oleic acid (abbreviated as OA)] systems and characterized them with optical observation, rheometry, and freeze-fracture transmission electron microscopy (FF-TEM) images. Bicontinuous and droplet-type O/W (oil-in-water) microemulsions are formed depending on the volume fraction of water. The bicontinuous structure observed in the oil-rich region, upon successive dilution with water, is transformed into a droplet-type microemulsion without phase separation. The prepared droplet-type microemulsion containing polymeric silicone and random copolymer PEPTME (38/10) as a cosurfactant in the water-rich region has potential applications in cosmetics.


Realizations of vascularized tissues: From in vitro platforms to in vivo grafts.
Vascularization is essential for realizing thick and functional tissue constructs that can be utilized for in vitro study platforms and in vivo grafts. The vasculature enables the transport of nutrients, oxygen, and wastes and is also indispensable to organ functional units such as the nephron filtration unit, the blood-air barrier, and the blood-brain barrier. This review aims to discuss the latest progress of organ-like vascularized constructs with specific functionalities and realizations even though they are not yet ready to be used as organ substitutes. First, the human vascular system is briefly introduced and related design considerations for engineering vascularized tissues are discussed. Second, up-to-date creation technologies for vascularized tissues are summarized and classified into the engineering and cellular self-assembly approaches. Third, recent applications ranging from in vitro tissue models, including generic vessel models, tumor models, and different human organ models such as heart, kidneys, liver, lungs, and brain, to prevascularized in vivo grafts for implantation and anastomosis are discussed in detail. The specific design considerations for the aforementioned applications are summarized and future perspectives regarding future clinical applications and commercialization are provided.


A preliminary investigation of the utilization of true metabolizable energy by chicks.
The change in carcass composition associated with intake of true metabolizable energy (TME) by young broiler chicks was investigated. The experiment comprised 17 treatments, 16 of which formed a 2 X 4 X 2 factorial design with six replications; the experimental unit was a pen of four male chicks. The factorial treatments consisted of two basal diets (lipogenic and proteogenic ), four levels of cellulose dilution (to cause a range of basal diet intakes), and two feeding periods (10 to 17 and 10 to 24 days of age). The birds were fed ad libitum, feed intake was recorded, and final carcass composition was measured. The 17th treatment comprised 24 pens of chicks killed at the start of the experiment to estimate initial carcass composition. The gross energy of carcass fat and protein was estimated by chemical and physical analysis and by regression analysis, the latter yielded estimates of 24.5 and 39.5 MJ/kg for protein and fat, respectively. Basal diet intake was reduced by more than 50% at the highest level of cellulose dilution and increased by about 60% when the feeding period was extended from 17 to 24 days. Pen weight gain and carcass composition were affected by basal diet intake. The energy retained in the carcass (MJ/W X 75 kg/day) (RE') increased in a linear manner with the intake of TME (MJ/W X 75 kg/day) ( ITME ), the slope of the line being greater for the lipogenic than for the proteogenic diet. Projected back to zero ITME ', the regression lines for pens in positive energy balance gave an estimate of .420 MJ loss, After 7 days on experiment, the energy retained as fat (RE'f) and as protein (RE'p) increased approximately linearly with ITME ', but after 14 days some curvature was apparent, the deposition of protein increasing more rapidly at the lower levels of energy input, and the deposition of fat increasing more rapidly at the higher levels of energy input. The RE'p was only slightly higher on the proteogenic diet than on the lipogenic diet, at the same level of ITME ', but the effect of basal diet on RE'f was considerable. For both diets at RE' = 0 there was gain in body protein accompanied by loss of body fat.


Low MUC4 expression is associated with survival benefit in patients with resectable pancreatic cancer receiving adjuvant gemcitabine.
Previous in vitro studies have shown that mucin 4 (MUC4) confers resistance toward gemcitabine in pancreatic cancer cells. To date, there are few clinical studies corroborating these findings. The aim of this study was to evaluate the predictive impact of MUC4 expression on survival in patients with resectable pancreatic cancer receiving adjuvant gemcitabine. MUC4 expression was investigated by immunohistochemistry in 78 tissue sections from patients with pancreatic ductal adenocarcinoma undergoing Whipple resection. The H-score was used to evaluate MUC4 expression. The Kaplan-Meier method and Cox proportional hazards regression analysis were used to assess the predictive role of MUC4 expression. The MUC4 protein was expressed in 93.6% (73/78) of pancreatic cancer tissue specimens. None of the normal control pancreatic tissues had any MUC4 expression. Low MUC4 expression (H-score ≤100) was detectable in 42 (53.8%) of tumors and high MUC4 expression (H-score >100) was detectable in 36 (46.2%) of tumors. Low expression of MUC4 was associated with favorable survival (p = .027), whereas high MUC4 expression did not correlate with survival (p = .87) in patients receiving adjuvant gemcitabine treatment. This is the first study indicating a predictive role of MUC4 expression for gemcitabine treatment in the clinical setting.


Loss of coxsackie and adenovirus receptor expression in human colorectal cancer: A potential impact on the efficacy of adenovirus-mediated gene therapy in Chinese Han population.
The coxsackie and adenovirus receptor (CAR) is considered a tumor suppressor and critical factor for the efficacy of therapeutic strategies that employ the adenovirus. However, data on CAR expression levels in colorectal cancer are conflicting and its clinical relevance remains to be elucidated. Immunohistochemistry was performed on tissue microarrays containing 251 pairs of colon cancer and adjacent normal tissue samples from Chinese Han patients to assess the expression levels of CAR. Compared with healthy mucosa, decreased CAR expression (40.6% vs. 95.6%; P<0.001) was observed in colorectal cancer samples. The CAR immunopositivity in tumor tissues was not significantly associated with gender, age, tumor size, differentiation, TNM stage, lymph node metastasis or distant metastasis in patients with colon cancer. However, expression of CAR is present in 83.3% of the tumor tissues from patient with colorectal liver metastasis, which was significantly higher than those without liver metastasis (39.6%; P=0.042). At the plasma membrane, CAR was observed in 29.5% normal mucosa samples, which was significantly higher than in colorectal cancer samples (4.0%; P<0.001). In addition, the survival analysis demonstrated that the expression level of CAR has no association with the prognosis of colorectal cancer. CAR expression was observed to be downregulated in colorectal cancer, and it exerts complex effects during colorectal carcinogenesis, potentially depending on the stage of the cancer development and progression. High CAR expression may promote liver metastasis. With regard to oncolytic therapy, CAR expression analysis should be performed prior to adenoviral oncolytic treatment to stratify Chinese Han patients for treatment.


The role of PGRN in musculoskeletal development and disease.
Progranulin (PGRN) is a growth factor that has been implicated in wound healing, inflammation, infection, tumorigenesis, and is most known for its neuroprotective and proliferative properties in neurodegenerative disease. This pleiotropic growth factor has been found to be a key player and regulator of a diverse spectrum of multi-systemic functions. Its critical anti-inflammatory role in rheumatoid arthritis and other inflammatory disease models has allowed for the propulsion of research to establish its significance in musculoskeletal diseases, including inflammatory conditions involving bone and cartilage pathology. In this review, we aim to elaborate on the emerging role of PGRN in the musculoskeletal system, reviewing its particular mechanisms described in various musculoskeletal diseases, with special focus on osteoarthritis and inflammatory joint disease patho-mechanisms and potential therapeutic applications of PGRN and its derivatives in these and other musculoskeletal diseases.


Quantifying Dynamic Changes in Plantar Pressure Gradient in Diabetics with Peripheral Neuropathy.
Diabetic foot ulcers remain one of the most serious complications of diabetes. Peak plantar pressure (PPP) and peak pressure gradient (PPG) during walking have been shown to be associated with the development of diabetic foot ulcers. To gain further insight into the mechanical etiology of diabetic foot ulcers, examination of the pressure gradient angle (PGA) has been recently proposed. The PGA quantifies directional variation or orientation of the pressure gradient during walking and provides a measure of whether pressure gradient patterns are concentrated or dispersed along the plantar surface. We hypothesized that diabetics at risk of foot ulceration would have smaller PGA in key plantar regions, suggesting less movement of the pressure gradient over time. A total of 27 participants were studied, including 19 diabetics with peripheral neuropathy and 8 non-diabetic control subjects. A foot pressure measurement system was used to measure plantar pressures during walking. PPP, PPG, and PGA were calculated for four foot regions - first toe (T1), first metatarsal head (M1), second metatarsal head (M2), and heel (HL). Consistent with prior studies, PPP and PPG were significantly larger in the diabetic group compared with non-diabetic controls in the T1 and M1 regions, but not M2 or HL. For example, PPP was 165% (P = 0.02) and PPG was 214% (P < 0.001) larger in T1. PGA was found to be significantly smaller in the diabetic group in T1 (46%, P = 0.04), suggesting a more concentrated pressure gradient pattern under the toe. The proposed PGA may improve our understanding of the role of pressure gradient on the risk of diabetic foot ulcers.


Muscone improves cardiac function in mice after myocardial infarction by alleviating cardiac macrophage-mediated chronic inflammation through inhibition of NF-κB and NLRP3 inflammasome.
Muscone is the main active monomer of traditional Chinese medicine musk. Previous studies have reported a variety of beneficial effects of muscone. However, the effects of muscone on chronic inflammation after myocardial infarction (MI) are rarely reported. This study evaluated the anti-inflammatory effects of muscone on myocardial infarction by establishing a MI model in mice. We found that muscone remarkably decreased the levels of inflammatory cytokines (IL-1β, TNF-α and IL-6), and ultimately improved cardiac function and survival rate. Furthermore, the main anti-inflammatory effect of muscone was alleviating cardiac macrophage-mediated inflammatory response in heart tissues after MI. Bone marrow-derived macrophages (BMDMs) induced with lipopolysaccharide (LPS) were used as an in vitro inflammation model to further clarify anti-inflammatory mechanisms of muscone. Muscone significantly downregulated the levels of LPS-induced inflammatory cytokines and inhibited NF-κB and NLRP3 inflammasome activation in BMDMs. Moreover, ROS and antioxidant indices in LPS-induced BMDMs were also ameliorated after muscone treatment. To sum up, our study found that muscone alleviated cardiac macrophage-mediated chronic inflammation by inhibiting NF-κB and NLRP3 inflammasome activation, thereby improving cardiac function in MI mice. Besides, the inhibitory effect of muscone on inflammation may be related to the scavenging of ROS. It is suggested that muscone may serve as a promising and effective drug for post-MI treatment.


Preparation of template free zinc oxide nanoparticles using sol-gel chemistry.
Zinc oxide (ZnO) nanoparticle has been synthesized via sol-gel chemistry using zinc acetate as a precursor with sodium hydroxide solution through microemulsion technique. X-ray diffraction (XRD) and transmission electron microscopy (TEM) studies reveal that the resultant zinc oxide nanoparticles are wurtzite type with the controlled morphology of nano triangular and half ellipsoid structures. Room temperature photoluminescence measurement of zinc oxide nanoparticles exhibits a strong green band at around 375 nm with excitation energy of 3.30 eV indicating oxygen vacancies on the surface of the nanoparticles.


Evaluation of methylprednisolone and triamcinolone for the induction and maintenance treatment of pruritus in allergic cats: a double-blinded, randomized, prospective study.
Oral triamcinolone (T) and methylprednisolone (M) have been recommended at various dosages for the control of pruritus associated with feline allergic dermatitis. The first objective was to determine effective dosages of methylprednisolone (Pfizer, New York, NY, USA) and triamcinolone (Boehringer Ingelheim Vetmedica, Inc., St Joseph, MO, USA) required to induce remission from pruritus associated with feline allergic dermatitis. The second objective was to compare efficacy of several different alternate day maintenance dosages. The third objective was to determine whether laboratory abnormalities occurred at effective dosages. Thirty-two client-owned allergic cats were randomly assigned to the M or T groups. Owners reported weekly on pruritus score and behavioural changes. Remission was defined as a pruritus score of ≤2/10, with 0 as the least and 10 as the most pruritic. Serum chemistry, complete blood count, fructosamine and urinalysis were assessed on day 0, at the end of the 7-14 day induction phase and at study completion. Mean once daily doses required for induction were 1.41 mg/kg for M and 0.18 mg/kg for T. Mean alternate day maintenance doses were 0.54 mg/kg for M and 0.08 mg/kg for T. There was a statistically significant decrease in eosinophils and increase in fructosamine for both groups from baseline to study completion. Fructosamine levels did not exceed the reference range in any case. These results suggest that triamcinolone is approximately seven times as potent as methylprednisolone, and that these dosages are efficacious and well tolerated for the control of pruritus in allergic cats.


A Novel Strategy for Efficient Agaro-Oligosaccharide Production Based on the Enzymatic Degradation of Crude Agarose in Flammeovirga pacifica WPAGA1.
To avoid conflict between biofuel and food resource production, marine macroalgae (main algal polysaccharides) have been suggested as potent feedstock for biofuel production. Flammeovirga pacifica WPAGA1, a typical marine polysaccharide-degrading bacterium, can utilize crude agarose as the sole carbon source. Transcriptomic analysis was performed to further investigate the metabolic pathway of environmental-friendly utilization of crude agarose in F. pacifica WPAGA1. All these enzymes were overexpressed in Escherichia coli BL21(DE3), and the purified enzymes were characterized in vitro. As a result, the pathway of crude agarose which is desulfurized and hydrolyzed by enzymes to produce fermentable sugar is clear. Interestingly, sole neoagarobiose (~450 mg/L) was produced from crude agarose as a feedstock using engineered E. coli BL21(DE3). This study firstly reveals the metabolic pathway of crude agarose in strain WPAGA1 and establishes a novel and environmental-friendly strategy for neoagarobiose production using crude agarose as cost-effective and non-food-based feedstock.


Late airway responses to antigen challenge in sensitized inbred rats.
We studied the magnitude and the time course of changes in pulmonary resistance (RL) after aerosol challenge with chicken ovalbumin (OA) of 15 sensitized, highly inbred Brown-Norway (BN) rats. Animals were actively sensitized and 2 wk later were challenged through the airways. Airway responses of sensitized animals were compared to those of 6 control animals challenged with sufficient methacholine (MCh) to at least double RL and to 4 unsensitized control rats challenged with OA. Ten of 15 rats in the experimental group displayed an early response (ER), defined as an increase in RL of at least 50% within 1 h of challenge. A late response (LR) was considered to have occurred when the value of RL exceeded the mean plus 2 standard deviations of all the measurements taken from 1 h after challenge to the end of the experiment. Two rats died less than 240 min after OA challenge with RL greater than 200% baseline. The remaining 13 were studied for a total duration that ranged from 390 to 720 min and of these animals 10 demonstrated LRs. Maximal RL during the LR after OA was 287 +/- 49% (SE) baseline (range, 129 to 760) versus 115 +/- 15% (75 to 176) for control animals after MCh (p less than 0.01) and 52 +/- 3% (51 to 142; p less than 0.01) for unsensitized control animals after OA. There was no correlation between the magnitude of ER and LR; 3 LRs occurred in the absence of detectable ERs. The median time to the peak of the LR was 450 min; median duration of LRs was 90 min (range, 30 to 135 min).(ABSTRACT TRUNCATED AT 250 WORDS)


Morphological and morphometric studies of the splenic antitumor immune response, elicited by liposome-covered soluble p53 kDa antigen, in chemically-induced rat colon cancer.
We evaluated the splenic morphometric changes in rats treated with carcinogen to study development of anti-cancer immune response. When liposome-covered soluble 53 kDa antigen (s53) was injected into these rats, significant tumor-suppression was seen and the percentage of tumor-free animals rose from 15.4% in non-vaccinated rats to 53.8%. In the spleens of carcinogen treated rats that did not develop tumors, activity of B lymphocytes increased significantly. This was manifested by the expansion of the germinal centers to 50.9% of the follicular area reflecting depletion of B cells, and the decrease of the mantle layer to 48.9% of the follicles. A similar picture was seen with T lymphocytes: the area of the marginal zone decreased to 55.2% of the T zone of the white pulp, and that of the periarterial lymph sheaths (PALS) to 33.6%. In tumor-bearing rats features of the immune decompensation were seen: the germinal centers increased to 96.5% of the follicular area, and the mantle layer and PALS decreased significantly. Vaccination prevented these effects, especially in tumor-bearing rats: the PALS occupies 30.4% of the white pulp and the marginal zone 56.1%, and the mantle layer occupied 58.1% of the follicular zone. Similar changes were found in vaccinated rats without tumors reflecting the compensatory character of the immune reaction in vaccinated rats. In conclusion, we found that treatment with carcinogen followed by vaccination with the s53-liposomes complex stimulated the activity of the splenic B, and to a lesser degree the T systems.


Balancing commercial and public interests.
Alarge number of randomized clinical trials with important health outcomes are completed each year. Those with favorable findings are typically reported and published rapidly, while the publication of those with unfavorable results is often delayed or given a positive "spin." This observation applies primarily to industry-sponsored trials. Our objectives are to discuss the responsibility of pharmaceutical firms to the public with respect to timely, complete, and unbiased information from all randomized clinical trials and to propose solutions for improvements. We believe that in addition to financial obligations to their shareholders, pharmaceutical companies have social responsibilities to the public and to health care providers. However, private markets do not reward or compel optimal disclosure of drug safety or inferiority information on a voluntary basis.A problem which has not previously been identified relates to non-comparability of drugs. A case report from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) illustrates how public interests may be violated due to failure to inform about drug inferiority. The current system for dissemination of relevant medical information could be improved if all involved parties collaborated fully. However, full disclosure of trial results is unlikely when research results are unfavorable to the firm. We conclude that expanded government regulations will be required for a satisfactory solution to the problem.


Towards response success prediction: An integrative approach using high-resolution fMRI and autonomic indices.
Brainstem and midbrain nuclei are closely linked to effective cognitive performance and autonomic function. In the present study, we aimed to investigate indices of successful and unsuccessful response inhibition paying particular attention to the interplay between locus coeruleus (LC), ventral tegmental area (VTA)/substantia nigra (SN) and, most importantly, peripheral markers. We aimed to get insight in the predictive value of neural and physiological signals in response inhibition. A total of 35 healthy controls were recruited from the local community and a typical task of behavioral response inhibition (Go/No-Go paradigm) was applied. We used high-resolution fMRI, advanced brainstem analyses and specifically corrected for respiratory signal and cardiac noise. Our main results characterize specific neural activation patterns during successful and unsuccessful response inhibition especially comprising the anterior cingulate as well as the medial and lateral prefrontal cortex. A significant activation of the dopaminergic nuclei (VTA/SN) was found during error processing, but not during response inhibition. Most remarkably, specific neural activation patterns (i.e., dorsal anterior cingulate cortex) as well as accompanying autonomic indices (i.e., skin conductance response (SCR)) were identified to hold predictive information on an individual's performance. In summary, the importance of the VTA/SN during error processing was shown. Furthermore, autonomic indices and specific neural activation patterns may contain valuable information to predict task performance.


Complete hydatidiform mole in women aged 40 to 49 years.
To describe the clinical course of women aged 40 to 49 presenting with complete hydatidiform mole. All cases of complete mole diagnosed at the New England Trophoblastic Disease Center were reviewed. A total of 82 patients met the study criteria. Study patients had a mean age of 44.2 years, gravidity of 4.6 and parity of 2.6. The mean hCG on presentation was 230,484 mIU/mL. Most patients presented with abnormal vaginal bleeding (77%). Of the 82 patients, 83% underwent dilation and curettage without prophylactic chemotherapy; 53% of those patients developed gestational trophoblastic neoplasia (GTN). Patients who developed GTN were significantly more likely both before and after evacuation to have higher hCG levels than those who did not. There were no GTN cases among patients receiving either prophylactic chemotherapy or upfront hysterectomy. Aggressive upfront therapy was associated with shortened time to hCG normalization and fewer lines of surgical or chemotherapeutic therapy. All women in their 40s with complete mole are at high risk for GTN and might benefit from aggressive upfront therapy. Those patients with hCG levels >175,000 mIU/mL constitute an "ultra-high-risk" group for whom prophylactic chemotherapy or hysterectomy should be especially considered.


Craniofacial dysmorphogenesis in transgenic mice.
While using transgenic mice to study the regulation of alpha-fetoprotein (AFP) it was noted that two different alpha-fetoprotein-chloramphenicol acetyl transferase (CAT) transgenes resulted in the appearance of craniofacial anomalies in 11% of the offspring derived from crosses between transgenic mice and nontransgenic mates. A total of 13 fetuses exhibited abnormalities; two are described in detail. Ninety-two percent of the affected fetuses had some form of mandibular abnormality while zygomatic and ossicular defects appeared in more than 40% of the specimens. Aglossia and aberrant musculature were also present in the most severely involved specimen. Eight of the affected fetuses were screened for the presence of the AFP-CAT plasmid and all were found to be heterozygous for the transgene. Since the probability that all 8 of the abnormal fetuses known to carry the CAT gene would have done so by chance was only 1 in 256, it may be assumed that these anomalies did not appear spontaneously, but were somehow created by the transgenic procedure. It is not known how the transgenic material led to the observed dysmorphogenetic pattern, but theoretically introduction of the AFP-CAT plasmid could have disrupted morphogenesis through the presence of the "foreign" CAT protein or a decrease in the availability of AFP. Since AFP levels were found to be normal in both the liver and the yolk sac of transgenic fetuses, it appears that the presence of CAT was responsible for the craniofacial anomalies described here.


Anaemia and depletion of iron stores as risk factors for postpartum depression: a literature review.
Iron-deficiency and anaemia are common in pregnant and postpartum women because of increasing iron demand and blood loss. Many women also enter pregnancy with pre-depleted iron stores. We reviewed the evidence linking anaemia and/or iron-deficiency to postpartum depression (PPD). We identified seventeen studies in four databases including randomized-controlled trials (RCTs) and observational studies assessing the impact of anaemia, iron-deficiency and iron supplementation on the risk of PPD. We extracted data on sample size, geographical region, obstetrical complications, measures of depression, haemoglobin, iron levels and intake of iron supplementation and critically appraised the results from the studies. Eight out of ten studies found higher risk for PPD (r - 0.19 to -0.43 and ORs 1.70-4.64) in anaemic women. Low ferritin in the postpartum period but not during pregnancy was associated with increased risk of PPD. Iron supplementation in the postpartum period decreased risk of PPD in four out of five studies, whereas it did not protect from PPD if given during pregnancy. Limitations include study heterogeneity, discrepancy of prevalence of PPD and usage of a screening tool for evaluation of PPD. Anaemia and/or iron-deficiency may contribute to PPD in at-risk women. Further studies should elucidate the association between these entities.


[A new method for the intravital assessment of the functional activity of the membrane transporters performing the efflux of antitumor preparations from the cells of solid tumor specimens].
A new method for intravital assessment of the functional activity of anticancer drug efflux transporters in intact solid tumor specimens was developed. The method is based on the well-known approach to the transporter functional evaluation by intracellular accumulation of antitumor drugs and particularly the anthracycline antibiotic doxorubicin (Dox). The main new point of the method providing investigation of intact solid tumor specimens which markedly simplified the procedure is the fact that the intratissue and intracellular accumulation of Dox is determined not by the level of the drug in the tissue but by its fluorescence decrease in the incubation medium. To assess just the intracellular content of Dox and to estimate the transporter functional activity, investigation of the influence of membrane transporter inhibitors such as verapamil (P-gp inhibitor) and sodium azide (inhibitor of all the energy-dependent ABC transporters) on the drug fluorescence decrease in the incubation medium is stipulated. The validity of such an approach was experimentally proved with the specimens of the Ehrlich solid tumor transplants in mice (a sensitive variant of the tumor and the tumor with induced drug resistance). Biopsy specimens of human breast tumors were investigated with the new method and functional activity of various efflux transporters was revealed: (1) only P-gp, (2) both P-gp and other ABC transporters, (3) only transporters different from P-gp, (4) no functional activity of efflux transporters. The main trends of the further investigation of efflux transporter functional activity in human solid tumors possible for the first time with the use of the new method are defined.


Can established cultured papilloma cells harbor bovine papillomavirus?
Papillomaviruses have been reported to be very difficult to grow in cell culture. Also, there are no descriptions of cell cultures from lesions of bovine cutaneous papillomatosis, with identification of different bovine papilloma virus (BPV) DNA sequences. In the present report, we describe primary cell cultures from samples of cutaneous lesions (warts). We investigated the simultaneous presence of different BPV DNA sequences, comparing the original lesion to different passages of the cell cultures and to peripheral blood. BPV 1, 2 and 4 DNA sequences were found in lesion samples, and respective cell cultures and peripheral blood, supporting our previous hypothesis of the possible activity of these sequences in different samples and now also showing how they can be maintained in different passages of cell cultures.


Mumps with laboratory signs of subclinical pancreatitis may cause a disturbed beta-cell function.
Mumps epidemics are followed by sporadic cases of insulin dependent diabetes mellitus (IDDM). We have studied beta-cell function in 11 subjects who had had a mumps infection. They had no clinical pancreatitis but were selected as they had abnormal pancreas iso-amylase values and/or glucosuria during the mumps virus infection. At the follow-up some years later the subjects were healthy. A few HbA1-values were noted in the upper part of the normal range. Total serum insulin values were normal, but the C-peptide values were low at first follow-up 1-3 years after infection in all but two patients. These values increased in 4/7 patients during the follow-up period but were subnormal in five subjects still 3-6 years after the infection. All five patients had HLA-DR 3 and/or 4. In 7 out of 11 patients islet cell surface antibodies could be demonstrated. Our results indicate that subclinical mumps pancreatitis may initiate a reaction towards the beta-cells recognized as subnormal C-peptide levels several years later in certain patients. This might contribute to manifest IDDM many years after infection.


Effects of preoperative aspirin on perioperative platelet activation and dysfunction in patients undergoing off-pump coronary artery bypass graft surgery: A prospective randomized study.
The benefit of aspirin use after coronary artery bypass graft surgery has been well proven. However, the effect of preoperative aspirin use in patients undergoing off-pump coronary artery bypass graft surgery (OPCAB) has not been evaluated sufficiently. To evaluate platelet function changes during OPCAB due to preoperative aspirin use, we conducted a randomized controlled trial using flow cytometry and the Multiplate® analyzer. Forty-eight patients scheduled for elective OPCAB were randomized to the aspirin continuation (100 mg/day until operative day) and discontinuation (4 days before the operative day) groups. Platelet function was measured using the platelet activation markers CD62P, CD63, and PAC-1 by flow cytometry, and platelet aggregation was measured using the Multiplate® analyzer, after the induction of anesthesia (baseline), at the end of the operation, and 24 and 48 h postoperatively. Findings of conventional coagulation assays, thromboelastography by ROTEM® assays, and postoperative bleeding-related clinical outcomes were compared between groups. No significant change in CD62P, CD63, or PAC-1 was observed at the end of the operation or 24 or 48 h postoperatively compared with baseline in either group. The area under the curve for arachidonic acid-stimulated platelet aggregation, measured by the Multiplate® analyzer, was significantly smaller in the aspirin continuation group (P < 0.01). However, chest tube drainage and intraoperative and postoperative transfusion requirements did not differ between groups. Our study showed that preoperative use of aspirin for OPCAB did not affect perioperative platelet activation, but it impaired platelet aggregation, which did not affect postoperative bleeding, by arachidonic acid.


Efficacy of oral sotalol in suppression of premature ventricular complexes and analysis of its beta-adrenergic blocking activity.
The efficacy of oral DL-sotalol in suppressing premature ventricular complexes was assessed by Holter recordings in 28 patients during short term (two weeks) and long term (two years) trials, and its beta-adrenergic blocking effects were evaluated by heart rate response to the Bruce treadmill stress test and plasma catecholamine increases upon active standing. Sotalol produced a significant decrease (more than 85%) in the number of premature ventricular complexes, during both short term (54%) of patients) and long term (39% of patients) trials. The doses employed in this study (320 mg/day) produced mild to moderate degrees of beta-adrenergic blockade as suggested by: a 20% reduction in the mean heart rate on 48 h Holter monitoring (P less than 0.0005); a 15 to 30% reduction in tachycardia induced by strenuous exercise; and a 12% reduction in standing-induced tachycardia. Under long term sotalol therapy the increase in plasma noradrenaline concentrations in response to active standing was not modified, but the increase in plasma adrenaline concentrations was greater than under baseline conditions (P less than 0.025). Both systolic and diastolic blood pressures significantly increased during long term sotalol administration (P less than 0.005 and P less than 0.025, respectively). However, blood pressure remained within the normotensive range during sotalol therapy. It was concluded that sotalol provides, at effective antiarrhythmic doses, a satisfactory level of beta-adrenergic blockade which during standing was associated with significant changes in adrenaline plasma increments.(ABSTRACT TRUNCATED AT 250 WORDS)


Transcriptome-wide analysis of jasmonate-treated BY-2 cells reveals new transcriptional regulators associated with alkaloid formation in tobacco.
Jasmonates (JAs) are well-known regulators of stress, defence, and secondary metabolism in plants, with JA perception triggering extensive transcriptional reprogramming, including both activation and/or repression of entire metabolic pathways. We performed RNA sequencing based transcriptomic profiling of tobacco BY-2 cells before and after treatment with methyl jasmonate (MeJA) to identify novel transcriptional regulators associated with alkaloid formation. A total of 107,140 unigenes were obtained through de novo assembly, and at least 33,213 transcripts (31%) encode proteins, in which 3419 transcription factors (TFs) were identified, representing 72 gene families, as well as 840 transcriptional regulators (TRs) distributed among 19 gene families. After MeJA treatment BY-2 cells, 7260 differentially expressed transcripts were characterised, which include 4443 MeJA-upregulated and 2817 MeJA-downregulated genes. Of these, 227 TFs/TRs in 36 families were specifically upregulated, and 102 TFs/TRs in 38 families were downregulated in MeJA-treated BY-2 cells. We further showed that the expression of 12 ethylene response factors and four basic helix-loop-helix factors increased at the transcriptional level after MeJA treatment in BY-2 cells and displayed specific expression patterns in nic mutants with or without MeJA treatments. Our data provide a catalogue of transcripts of tobacco BY-2 cells and benefit future study of JA-modulated regulation of secondary metabolism in tobacco.


Virgin olive oil administration improves the effect of aspirin on retinal vascular pattern in experimental diabetes mellitus.
The aim of the present study is to evaluate the possible influence of virgin olive oil (VOO) on the effect of acetylsalicylic acid (ASA) in platelet aggregation, prostanoid and NO production and retinal vascular pattern in rats with experimental type 1-like diabetes. We used 100 male Wistar rats that were distributed into five groups: (1) non-diabetic rats (NDR); (2) untreated diabetic rats (DR); (3) DR treated with ASA (2 mg/kg per d per os (p.o.)); (4) DR treated with VOO (0.5 ml/kg per d p.o.); (5) DR treated with ASA plus VOO. The duration of diabetes was 3 months, and each treatment was administered from the first day of diabetes. Variables that were quantified were platelet aggregation (I(max)), thromboxane B(2) (TxB(2)), aortic prostacyclin (6-keto-PGF(1alpha)) and NO, and the percentage of retina with horseradish peroxidase-permeable vessels (HRP-PV). Diabetic rats showed a higher I(max) (35 %) and TxB(2) (63 %) than NDR, and a lower 6-keto-PGF(1alpha), NO and HRP-PV than NDR ( - 74.6 %). ASA and VOO administration reduced these differences and prevented the percentage of HRP-PV ( - 59.7 % with ASA and - 46.7 % with VOO). The administration of ASA plus VOO showed a strong platelet inhibition (80.2 v. 23.4 % for VOO and 50.6 % for ASA+VOO, P < 0.0001), and reduced HRP-PV differences to - 31.6 % (P < 0.001 with respect to DR and P < 0.0001 with respect to DR treated with ASA). In conclusion, the administration of VOO to rats with type 1-like diabetes mellitus improves the pharmacodynamic profile of ASA, and increases its retinal anti-ischaemic effect.


Sexual dimorphism and age of Mediterranean salamanders.
We analysed sexual size dimorphism (SSD) for two Mediterranean species of the "true" salamander clade possessing distinct life histories (Salamandra algira and Mertensiella caucasica) and equilibrated the morphometric approach to individual age by using skeletochronology. For species that have a short breeding season and live at high altitudes, such as Mediterranean amphibians, the fecundity advantage hypothesis predicts female-biased SSD to maximise reproductive success. Our results showed no SSD in either species; however, morphometric data indicated a male-biased dimorphism in limb (arm and leg) dimensions in both species when compared to body size. Limb dimorphisms are likely related to the particular mating system, which involves an amplexus during spermatophore transfer. Arm length appeared sexually dimorphic during ontogeny both in viviparous S. algira and oviparous M. caucasica. A review on SSD indicated monomorphy of body size as a common lineage-specific pattern among the "true" salamander clade, but also the common presence of other traits such as sexually dimorphic limb proportions.


Individual Differences in the Resistance to Social Change and Acceptance of Inequality Predict System Legitimacy Differently Depending on the Social Structure.
We propose that individual differences in the resistance to social change and the acceptance of inequality can have divergent effects on legitimacy depending on the context. This possibility was tested in a sample of 27 European countries (N = 144 367) and across four experiments (total N = 475). Individual differences in the resistance to social change were related to higher levels of perceived legitimacy no matter the level of inequality of the society. Conversely, individual differences in the acceptance of inequality were related to higher levels of perceived legitimacy in unequal societies, but either a relationship near zero or the opposite relationship was found in more equal societies. These studies highlight the importance of distinguishing between individual differences that make up political ideology, especially when making predictions in diverse settings. © 2017 The Authors. European Journal of Personality published by John Wiley & Sons Ltd on behalf of European Association of Personality Psychology.


Dedifferentiated human ventricular cardiac myocytes express inducible nitric oxide synthase mRNA but not protein in response to IL-1, TNF, IFNgamma, and LPS.
There is evidence that nitric oxide (NO) may mediate some of the functional myocardial changes caused by bacterial LPS and inflammatory cytokines. The expression of the inflammatory or inducible NO synthase (iNOS) in human cardiac myocytes, however, has not been well characterized. Therefore, we treated cultured, dedifferentiated human ventricular cardiac myocytes with the combination of TNF-alpha (500 U/ml), IL-1beta (30U/ml), IFNgamma (100 U/ml), and LPS (E.coli 0111:B4, 10 microg/ml). Northern blot analysis revealed a approximately 4.5 kb transcript for inducible NOS (iNOS) in the stimulated human heart cells but not in untreated cells. RT-PCR confirmed that iNOS mRNA was only present in stimulated cells. However, treatment of the myocytes for up to 96 h with cytokines and LPS did not result in NO synthesis as measured by nitrite + nitrate accumulation in the culture medium, and no iNOS enzymatic activity could be detected in the cell lysates. Western blot analysis failed to detect iNOS protein. Thus, despite high and persistent levels of iNOS mRNA in cytokine-treated cells, iNOS protein was absent in this experimental model. GTP-cyclohydrolase I was induced both at the mRNA and protein levels and resulted in increased biopterin levels, indicating sufficient amounts of the cofactor tetrahydrobiopterin (BH4) were present, and that the failure to express an inducible protein was specific to iNOS. To determine if the absence of iNOS protein was due to a novel cardiac iNOS gene or modified iNOS transcript in human myocytes, we cloned an iNOS cDNA from cytokine-treated myocytes. Sequencing and expression of the clone revealed a functional iNOS cDNA with >99% identity to other human iNOS cDNA clones. When human cardiac cells were transduced with a retroviral vector carrying only the coding region of the human hepatocyte iNOS cDNA, both iNOS mRNA and protein could be detected. In conclusion, these cells derived from cultured human cardiac myocytes lacked the capacity to express an endogenous iNOS protein, the basis of which appears to be a cell-specific suppression or failure of iNOS translation.


A fast-reciprocating probe array for two-dimensional measurements in the divertor region of the Tokamak à configuration variable.
A detailed description of the construction and commissioning of the fast-moving reciprocating divertor Langmuir probe array on the Tokamak à Configuration Variable (TCV) is presented. A horizontal array of 24 Langmuir probes (12 Mach probes) combined with a fast vertical movement provides unprecedented two-dimensional measurements of the plasma properties across the entire divertor outer leg volume and up to the X-point. The L-shape probe arm has to be very compact to minimize plasma perturbations and, at the same time, has to house 24 coaxial transmission lines, withstand time-averaged heat fluxes of up to ≈30 MW/m2 and accelerations of up to 8 g, and be resilient to violent plasma disruptions. For the fast vertical motion of the probe arm, extending up to 38 cm into the TCV vacuum vessel, an assembly with a precise and powerful linear electric motor (up to 4000 N of force) was mounted in a 4 m high structure within the limited space below the TCV. The diagnostic has already performed measurements in ≈200 plasma discharges and has been hit by ≈20 disruptions without suffering any critical damage. The measurements are qualitatively and quantitatively consistent with other reference diagnostics, such as upstream electron Thomson scattering and downstream wall-embedded Langmuir probes, and are used extensively on the TCV for experimental divertor studies and for comparisons with edge transport and turbulence code results.