The Emerging Role of Gut Microbiota in Age-Related Macular Degeneration.
Age-related macular degeneration (AMD) is a progressive, degenerative retinal disease that is a leading cause of blindness globally. Although multiple risk factors have been identified regarding disease incidence and progression, including smoking, genetics, and diet, the understanding of AMD pathogenesis remains unclear. As such, primary prevention is lacking, and current treatments have limited efficacy. More recently, the gut microbiome has emerged as an influential player in various ocular pathologies. As mediators of metabolism and immune regulation, perturbations in gut microbiota may impart significant effects distally on the neuroretina and its adjacent tissues, termed the gut-retina axis. In this review, key studies over the past several decades are summarized, both in humans and in animal models, which shed insight on the relationships between the gut microbiome and retinal biology and their implications for AMD. The literature linking gut dysbiosis with AMD is examined, along with preclinical animal models and techniques apt for studying the role of gut microbiota in AMD pathogenesis, which include interactions with systemic inflammation, immune regulation, chorioretinal gene expression, and diet. As understanding of the gut-retina axis continues to advance, so too will the possibility for more accessible and effective prevention and therapy of this vision-threatening condition.


Analyzing modal behavior of guided waves using high order eigenvalue derivatives.
This paper presents a mode-tracing approach for elastic guided waves based on analytically computed derivatives and includes a study of interesting phenomena in the dispersion curve representation. Numerical simulation is done by means of the Scaled Boundary Finite Element Method (SBFEM). Two approaches are used to identify the characteristics of the resulting wave modes: Taylor approximation and Padé approximation. Higher order differentials of the underlying eigenvalue problem are the basis for these approaches. Remarkable phenomena in potentially critical frequency regions are identified and the tracing approach is adapted to these regions. Additionally, a stabilization of the solution process is suggested.


Clock mutation lengthens the circadian period without damping rhythms in individual SCN neurons.
Spontaneous discharges of individual neurons in the suprachiasmatic nucleus (SCN) of Clock mutant mice were recorded for over 5 days in organotypic slice cultures and dispersed cell cultures using a multi-electrode dish. Circadian rhythms with periods of about 27 hours were detected in 77% of slice cultures and 15% of dispersed cell cultures derived from Clock/Clock homozygotes. These findings indicate that the Clock mutation lengthens the circadian period but does not abolish the circadian oscillation, and suggest an important role of intercellular communication in the expression of circadian rhythm in the SCN.


Ultra-selective carbon nanotubes for photoacoustic imaging of inflamed atherosclerotic plaques.
Disruption of vulnerable atherosclerotic plaques often leads to myocardial infarction and stroke, the leading causes of morbidity and mortality in the United States. A diagnostic method that detects high-risk atherosclerotic plaques at early stages could prevent these sequelae. The abundance of immune cells in the arterial wall, especially inflammatory Ly-6Chi monocytes and foamy macrophages, is indicative of plaque inflammation, and may be associated with plaque vulnerability. Hence, we sought to develop a new method that specifically targets these immune cells to offer clinically-relevant diagnostic information about cardiovascular disease. We combine ultra-selective nanoparticle targeting of Ly-6Chi monocytes and foamy macrophages with clinically-viable photoacoustic imaging (PAI) in order to precisely and specifically image inflamed plaques ex vivo in a mouse model that mimics human vulnerable plaques histopathologically. Within the plaques, high-dimensional single-cell flow cytometry (13-parameter) showed that our nanoparticles were almost-exclusively taken up by the Ly-6Chi monocytes and foamy macrophages that heavily infiltrate plaques. PAI identified inflamed atherosclerotic plaques that display ~6-fold greater signal compared to controls (P<0.001) six hours after intravenous injection of ultra-selective carbon nanotubes, with in vivo corroboration via optical imaging. Our highly selective strategy may provide a targeted, non-invasive imaging strategy to accurately identify and diagnose inflamed atherosclerotic lesions.


Decreased hepatic 5-HT1A receptors during liver regeneration and neoplasia in rats.
In the present study we investigated the role of 5-hydroxytryptamine (5-HT) and 5-HT1A receptor during liver regeneration after partial hepatectomy (PH) and N-nitrosodiethylamine (NDEA) induced hepatocellular carcinoma in male Wistar rats. 5-HT content was significantly increased during liver regeneration after PH and NDEA induced hepatocellular carcinoma. Scatchard analysis using 8-OH-DPAT, a 5-HT1A specific agonist showed a decreased receptor during liver regeneration after PH and NDEA induced hepatocellular carcinoma. 5-HT when added alone to primary hepatocyte culture did not increase DNA synthesis but was able to increase the EGF mediated DNA synthesis and inhibit the TGF beta 1 mediated DNA synthesis suppression in vitro. This confirmed the co-mitogenic activity of 5-HT. 8-OH-DPAT at a concentration of 10(-4) M inhibited the basal and EGF-mediated DNA synthesis in primary hepatocyte cultures. It also suppressed the TGF beta 1-mediated DNA synthesis suppression. This clearly showed that activated 5-HT1A receptor inhibited hepatocyte DNA synthesis. Our results suggest that decreased hepatic 5-HT1A receptor function during hepatocyte regeneration and neoplasia has clinical significance in the control of cell proliferation.


Postpartum depression, a direct and mediating risk factor for preschool wheeze in girls.
Postpartum depression affects over 1 in 10 child-bearing women. A growing body of evidence links maternal distress during the key developmental stages of infants with poor health outcomes, including wheeze and asthma. We sought to investigate whether postpartum depression had an independent association with the development of wheeze in preschool-aged children. A second a priori objective was to ascertain whether postpartum depression functioned as a mediating factor for associations between wheeze, and prenatal distress and nutrition. Data from the Community Perinatal Care Trial on maternal postpartum depression (Edinburgh Postnatal Depression Scale), the dependent variable, wheeze at age 3, and possible confounding factors were obtained for 791 women and their children in Calgary, Canada. Adjusted gender-specific logistic regression analyses were performed to test the association between postpartum depression and child wheeze, which was independent of maternal distress and vitamin use during pregnancy, pre/postnatal smoking, preterm birth, exclusive breastfeeding duration, daycare attendance, and maternal education. The potential mediating effects of postpartum depression were investigated in a path analysis. Wheeze at age 3 was almost 5 times more likely in girls of mothers who experienced postpartum depression. Results from a path analysis suggested that postpartum depression has a direct effect on wheeze (beta-coefficient=0.135, P < 0.05), and also mediates the effects of prenatal distress and vitamin use on wheeze in preschool girls. In boys, only prenatal smoking was a statistically significant predictor of wheeze, mainly through the effects of postnatal smoking. Postpartum depression may be a risk factor for preschool wheeze among girls in a low risk population, directly and indirectly through prenatal distress and vitamin use. Interventions which target postpartum depression and promote a healthy pregnancy may also reduce the risk of wheeze in children.


Computerized axial tomography for the diagnosis of cerebral cysticercosis.
Computerized Axial Tomography (CAT) has proved extremely useful for the diagnosis of cerebral cysticercosis. The calcified small, multiple, and scattered cysts provide a typical image on CAT. The collection of non-calcified cysts in the subarachnoid spaces (racemose form) or in the ventricles may produce areas of low density similar to that of the cerebrospinal fluid. The dilatation of the ventricular system, extreme degrees of hydrocephalus, areas of cerebral atrophy, and other related changes induced by the cysts in the subarachnoid spaces are also clearly shown in the CAT. Four personal cases are reported.


Recombinant production of the insecticidal scorpion toxin BjαIT in Escherichia coli.
Scorpion long-chain insect neurotoxins have important potential application value in agricultural pest control. The difficulty of obtaining natural toxins is the major obstacle preventing analyses of their insecticidal activity against more agricultural insect pests. Here we cloned the insect neurotoxin BjαIT gene into the pET32 expression vector and expressed the resulting thioredoxin (Trx)-BjαIT fusion protein in Escherichia coli. Soluble Trx-BjαIT was expressed at a high level when induced at 18 °C with 0.1 mM isopropyl β-d-1-thiogalactopyranoside, and it was purified by Ni2+-nitriloacetic acid affinity chromatography. After cleaving the Trx tag with recombinant enterokinase, the digestion products were purified by CM Sepharose FF ion-exchange chromatography, and 1.5 mg of purified recombinant BjαIT (rBjαIT) was obtained from 100 ml of induced bacterial cells. Injecting rBjαIT induced obvious neurotoxic symptoms and led to death in locust (Locusta migratoria) larvae. Dietary toxicity was not observed in locusts. The results demonstrate that active rBjαIT could be obtained efficiently from an E. coli expression system, which is helpful for determining its insecticidal activity against agricultural insect pests.


Chromatin Immunostaining of Plant Nuclei.
Recent evidence has demonstrated that specific epigenetic changes are also related to plant growth and development. Immunostaining enables the detection and characterization of chromatin modification, e.g., histone H4 acetylation (H4K5ac), histone H3 methylation (H3K4me2 and H3K9me2), and DNA methylation (5mC) with unique and specific patterns in plant tissues. Here we describe experimental procedures to determine the histone H3 methylation (H3K4me2 and H3K9me2) patterns in 3D-chromatin in whole roots tissue and 2D-chromatin in single nuclei in rice. To analyze both iron and salinity treatments, we show how to test for changes to the epigenetic chromatin landscape using heterochromatin (H3K9me2) and euchromatin (H3K4me) markers for chromatin immunostaining, especially in the proximal meristem region. To elucidate the epigenetic impact of environmental stress and external plant growth regulators, we demonstrate how to apply a combination of salinity, auxin, and abscisic acid treatments. The results of these experiments provide insights into the epigenetic landscape during rice root growth and development.


The role of polymeric nanofibers on the mechanical behavior of polymethyl methacrylate resin.
This study aimed to synthesize and characterize non-woven acrylonitrile butadiene styrene (ABS), polyamide-6 (P6), and polystyrene (PS) nanofibers, and evaluate their effects on the flexural strength and fracture resistance of fiber-modified polymethyl methacrylate (PMMA) resin. ABS, P6, and PS polymer solutions were prepared and electrospun into fiber mats, which were characterized by means of morphological, chemical, physical, and mechanical analyses. The fiber mats were then used to modify a thermally-activated PMMA resin, resulting in four testing groups: one unmodified group (control) and three fiber-modified groups incorporated with ABS, P6, or PS fiber mats. Flexural strength, work of fracture, and fractographic analysis were performed for all groups. Data were analyzed using Kruskal-Wallis or ANOVA tests (α = 0.05). The fiber diameter decreased, respectively, as follows: ABS > P6 > PS. Only the P6 fiber mats demonstrated a crystalline structure. Wettability was similar among the distinct fiber mats, although tensile strength was significantly greater for P6, followed by ABS, and then PS mats. Flexural strength of the fiber-modified PMMA resins was similar to the control, except for the weaker P6-based material. The work of fracture seemed to be greater and lower when the P6 and PS fibers were used, respectively. The fiber-modified groups exhibited a rougher pattern in the fractured surfaces when compared to the control, which may suggest that the presence of fibers deviates the direction of crack propagation, making the fracture mechanism of the PMMA resin more dynamic. While the neat PMMA showed a typical brittle response, the fiber-modified PMMA resins demonstrated a ductile response, combined with voids, suggesting large shear deformation during fracture. Altogether, despite the lack of direct reinforcement in the mechanical strength of the PMMA resin, the use of electrospun fibers showed promising application for the improvement of fracture behavior of PMMA resins, turning them into more compliant materials, although this effect may depend on the fiber composition.


Reconsidering pluripotency tests: do we still need teratoma assays?
The induction of teratoma in mice by the transplantation of stem cells into extra-uterine sites has been used as a read-out for cellular pluripotency since the initial description of this phenomenon in 1954. Since then, the teratoma assay has remained the assay of choice to demonstrate pluripotency, gaining prominence during the recent hype surrounding human stem cell research. However, the scientific significance of the teratoma assay has been debated due to the fact that transplanted cells are exposed to a non-physiological environment. Since many mice are used for a result that is heavily questioned, it is time to reconsider the teratoma assay from an ethical point of view. Candidate alternatives to the teratoma assay comprise the directed differentiation of pluripotent stem cells into organotypic cells, differentiation of cells in embryoid bodies, the analysis of pluripotency-associated biomarkers with high correlation to the teratoma forming potential of stem cells, predictive epigenetic footprints, or a combination of these technologies. Each of these assays is capable of addressing one or more aspects of pluripotency, however it is essential that these assays are validated to provide an accepted robust, reproducible alternative. In particular, the rapidly expanding number of human induced pluripotent stem cell lines, requires the development of simple, affordable standardized in vitro and in silico assays to reduce the number of animal experiments performed.


Change in circulating microRNA profile of obese children indicates future risk of adult diabetes.
Childhood obesity increases susceptibility to type 2 diabetes (T2D) in adults. Circulating microRNAs (miRNAs) in serum have been proposed as potential diagnostic biomarkers, and they may contribute to the progression toward T2D. Here, we investigated the possibility of predicting the future risk of adult T2D in obese children by using circulating miRNAs. We performed miRNA high-throughput sequencing to screen relevant circulating miRNAs in obese children. The expression patterns of targeted miRNAs were further explored in obese children and adults with T2D. To investigate the underlying contributions of these miRNAs to the development of T2D, we detected the impacts of the candidate miRNAs on preadipocyte proliferation, insulin secretion by pancreatic β-cell, and glucose uptake by skeletal muscle cells. Three miRNAs (miR-486, miR-146b and miR-15b), whose expression in the circulation was most dramatically augmented in obese children and adult T2D patients, were selected for further investigation. Of these 3 miRNAs, miR-486 was implicated in accelerating preadipocyte proliferation and myotube glucose intolerance, miR-146b and miR-15b were engaged in the suppression of high concentration glucose-induced pancreatic insulin secretion, and they all contributed to the pathological processes of obesity and T2D. Our results provide a better understanding of the role of circulating miRNAs, particularly miR-486, miR-146b and miR-15b, in predicting the future risk of T2D in obese children.


Design, fabrication and application of self-spiraling pattern-driven 4D-printed actuator.
Self-spiraling actuators are widely found in nature and have high research and actuator-application value in self-lock and self-assembly. Four-dimensional (4D) printing is a new generation additive manufacturing of smart materials and has shown great potential for the fabrication of multi-functional and customized structures. The microarchitecture design of a bilayer actuator could bring flexible and diversified self-spiraling behaviors and more possibilities for practical application by combing 4D printing. This work investigates the stimuli effects of fiber patterns and fabrication parameters on self-spiraling behaviors of the bilayer actuator via both experimental and theoretical methods. This work may potentially provide pattern design guidance for 4D-printed self-spiraling actuators to meet different application requirements.


Evaluation of Drug Utilization Patterns during Initial Treatment in the Emergency Room: A Retroprospective Pharmacoepidemiological Study.
Background. We assessed the prescribing trends, average number of drugs per prescription, and cost per prescription during the initial contact of the patient with the physician in emergency room. Methods. This retro-prospective study was conducted over a period of six months. Medical records of two hundred patients were reviewed for prescribing patterns. Results. 52 different types of drugs (996 drugs) were prescribed in total 200 prescriptions during the mean time spent in emergency room of 2.8 ± 1.4 hours. The average number of drugs per prescription was 4.2 ± 1.2. 95% of drugs were prescribed by trade name. Average drugs cost per prescription was 784 ± 134 rupees (17USD). Conclusion. Polypharmacy remains the main form of irrational prescribing. Prescribing patterns of drugs were knowledge based rather than WHO criteria for rational use of drugs.


Helcococcus ovis isolated from a goat with purulent bronchopneumonia and pulmonary abscesses.
The current study describes the recovery of Helcococcus ovis from an adult female Verata breed goat that was euthanized because of respiratory problems and emaciation. At necropsy, the affected animal showed a purulent bronchopneumonia with scattered pulmonary abscesses and fibrous pleural adhesions. A Gram-positive, catalase-negative, coccus-shaped bacterium was isolated from the lung tissue and confirmed as H. ovis by 16S ribosomal RNA gene sequencing.


Changes in pro-inflammatory markers and leucine concentrations in response to Nordic Walking training combined with vitamin D supplementation in elderly women.
Mechanisms underpinning age-related decreases in muscle strength and muscle mass relate to chronic inflammation. Physical activity induces an anti-inflammatory effect, but it is modulated by additional factors. We hypothesized that vitamin D, which has also anti-inflammatory activity will modify adaptation to exercise and reduce inflammation in elderly women. Twenty-seven women aged 67 ± 8 years were included and divided into groups with baseline vitamin D concentration more than 20 ng mL-1 (MVD) and less than 20 ng mL-1 (LVD). Both groups performed 1 h Nordic Walking (NW) training combined with vitamin D supplementation for 12 weeks. Serum concentrations of inflammation markers, branched amino acids, vitamin D, muscle strength and balance were assessed at the baseline and three days after intervention. The training caused the significant decrease in concentration of pro-inflammatory proteins HMGB1 (30 ± 156%; 90% CI) and IL-6 (-10 ± 66%; 90% CI) in MVD group. This effects in group MVD were moderate, indicating vitamin D as one of the modifiers of these exercise-induced changes. Rise of myokine irisin induced by exercise correlated inversely with HMGB1 and the correlation was more pronounced at the baseline as well as after training among MVD participants. Although the intervention caused the leucine level to rise, a comparison of the recorded response between groups and the adjusted effect indicated that the effect was 20% lower in the LVD group. Overall the applied training program was effective in reducing HMGB1 concentration. This drop was accompanied by the rise of myokine irisin and better uptake of leucine among women with higher baseline vitamin D.


Bullet Embolism into the Common Iliac Artery from a Gunshot Wound to the Heart.
We describe the management of bullet embolism from a penetrating cardiac injury, including the clinical, radiographic, and operative considerations in this challenging trauma scenario. Bullet embolism represents a rare but complex subset of ballistic penetrating trauma, and highlights the importance of radiographic correlation with intraoperative findings.


Use and cost of disease-modifying therapies by Sonya Slifka Study participants: has anything really changed since 2000 and 2009?
Disease-modifying therapies benefit individuals with relapsing forms of multiple sclerosis, but their utility remains unclear for those without relapses. To determine disease-modifying therapy use and costs in 2009, compare use in 2009 and 2000, and examine compliance with evidence-based guidelines. We determined the extent and characteristics of disease-modifying therapy use by participants in the Sonya Slifka Longitudinal Multiple Sclerosis Study (Slifka) in 2000 (n=2156) and 2009 (n=2361) and estimated out-of-pocket and total (payer) costs for 2009. Two multivariable logistic regressions predicted disease-modifying therapy use. Disease-modifying therapy use increased from 55.3% in 2000 to 61.5% in 2009. In 2009, disease-modifying therapy use was reported by 76.5% of participants with relapsing-remitting multiple sclerosis, 73.2% with progressive-relapsing multiple sclerosis, 62.5% with secondary progressive multiple sclerosis, and 41.8% with primary progressive multiple sclerosis. Use was significantly associated with relapsing-remitting multiple sclerosis, shorter duration of illness, one to two relapses per year, non-ambulatory symptoms, using a cane, younger age, higher family income, and having health insurance. Average annual costs in 2009 were US$939-3101 for patients and US$16,302-18,928 for payers. Use rates were highest for individuals with relapsing-remitting multiple sclerosis, but substantial for those with progressive courses although clinical trials have not demonstrated significant benefits for them.


MLL translocations, histone modifications and leukaemia stem-cell development.
Translocations that involve the mixed lineage leukaemia (MLL) gene identify a unique group of acute leukaemias, and often predict a poor prognosis. The MLL gene encodes a DNA-binding protein that methylates histone H3 lysine 4 (H3K4), and positively regulates gene expression including multiple Hox genes. Leukaemogenic MLL translocations encode MLL fusion proteins that have lost H3K4 methyltransferase activity. A key feature of MLL fusion proteins is their ability to efficiently transform haematopoietic cells into leukaemia stem cells. The link between a chromatin modulator and leukaemia stem cells provides support for epigenetic landscapes as an important part of leukaemia and normal stem-cell development.


Sodium-losing nephropathy and nephrocalcinosis after transplantation.
Severe, prolonged sodium-wasting (up to 38% FENa) occurred in a man after he received a cadaveric-donor kidney. Posttransplantation supplementation with large amounts of saline and/or salt tablets was mandatory. Fludrocortisone had no clinically apparent effect. Plasma renin activity and plasma aldosterone concentration were markedly increased. As chronic rejection progressed, the syndrome ameliorated. Renal biopsy showed cellular rejection and nephrocalcinosis.


Enhancement of aldose reductase activity by modification of an active site lysine: a possible mechanism for in vivo activation.
Reaction of aldose reductase (ALR2) from pig muscle with pyridoxal 5'-phosphate (pyridoxal-P) and other lysine modifying reagents resulted in activation of the enzyme. The activation by pyridoxal-P showed pH and concentration dependence that was prevented by incubation with NADPH and various cofactor analogues but not by the aldehyde substrate. Spectral analysis of the reaction showed characteristic peaks associated with Schiff's base formation between a lysine amino group and the aldehyde of pyridoxal-P. Subsequent reduction produced spectra characteristic of a phosphopyridoxyllysine bond. Phosphopyridoxyllysine was isolated by amino acid analysis of modified ALR2. Determination of the stoichiometry of bound phosphopyridoxyllysine indicated one mole of pyridoxal-P per mole of enzyme under conditions that produced maximal activation. A single [3H]phosphopyridoxyllysine containing peptide was isolated by high performance liquid chromatography after enzymatic cleavage of the modified enzyme. This 34 residue peptide exhibited considerable sequence homology to the region comprising residues 242 to 275 of human liver ALR1 and a similar region in rat lens ALR2, human muscle ALR2 and human placental ALR2. The activation of ALR2 via formation of a Schiff's base suggests a possible mechanism of activation of the enzyme in vivo by glucose.


201Tl for the differential diagnosis of cold thyroid nodules.
We used 201Tl-chloride for studying and differentiating thyroid areas shown to be 'cold' in previous 131I or 99mTc scanning. We investigated sixteen thyroid neoplasms that were removed surgically shortly afterwards. We found an intense intranodular accumulation of 301T1 in five scintigraphs shown to be of histologically malignant neoplasms, and an intense accumulation also in one of those shown to be histologically benign. We did not detect any 201Tl-chloride accumulation in two cases of thyroiditis; one of these had shown an intense accumulation in a previous 131Cs scintigram.


[Evaluation of Doppler sonographic criteria for the differentiation of hepatocellular carcinomas and regenerative nodules in patients with liver cirrhosis].
In order to improve the differentiation between hepatocellular carcinomas and regenerative nodules in patients with liver cirrhosis, Doppler-sonographic criteria for the tumours were evaluated. Patients with histologically proven hepatocellular carcinoma (n = 35) and regenerative nodules (n = 10) were investigated by B-mode sonography as well as fundamental and echo-enhanced power-Doppler sonography focusing on specific properties of the tumours. The results were correlated to the histological findings. Hepatocellular carcinomas and regenerative nodules showed a different contrast behaviour with echo-enhanced power-Doppler sonography. The following features of hepatocellular carcinomas were frequently found: peritumoural signal detection in the early arterial phase, chaotic and centripetal contrast enhancement in the arterial phase, hypervascularization in the capillary phase, and loss of portalvenous blood flow. Hepatocellular carcinomas and regenerative nodules display different vascularization patterns in the echo-enhanced power-Doppler sonography. These characteristics can be useful for their differential diagnosis.


Inhibition of phosphorylated STAT3 by cucurbitacin I enhances chemoradiosensitivity in medulloblastoma-derived cancer stem cells.
CD133 (PROM1) is a potential marker for cancer stem cells (CSCs), including those found in brain tumors. Recently, medulloblastoma (MB)-derived CD133-positive cells were found to have CSC-like properties and were proposed to be important contributors to tumorigenicity, cancer progression, and chemoradioresistance. However, the biomolecular pathways and therapeutic targets specific to MB-derived CSCs remain unresolved. In the present study, we isolated CD133(+) cells from MB cell lines and determined that they showed increased tumorigenicity, radioresistance, and higher expression of both embryonic stem cell-related and drug resistance-related genes compared to CD133(-) cells. Bioinformatics analysis suggested that the STAT3 pathway might be important in MB and CD133(+) cells. To evaluate the effects of inhibiting the STAT3 pathway, MB-derived CD133(+/-) cells were treated with the potent STAT3 inhibitor, cucurbitacin I. Treatment with cucurbitacin I significantly suppressed the CSC-like properties and stemness gene signature of MB-derived CD133(+) cells. Furthermore, cucurbitacin I treatment increased the apoptotic sensitivity of MB-derived CD133(+) cells to radiation and chemotherapeutic drugs. Notably, cucurbitacin I demonstrated synergistic effects with ionizing radiation to inhibit tumorigenicity in MB-CD133(+)-inoculated mice. These results indicate that the STAT3 pathway plays a key role in mediating CSC properties in MB-derived CD133(+) cells. Targeting STAT3 with cucurbitacin I may therefore represent a novel therapeutic approach for treating malignant brain tumors.


Quantifying patch-specific seed dispersal and local population dynamics to estimate population spread of an endangered plant species.
Habitat loss and fragmentation impose high extinction risk upon endangered plant species globally. For many endangered plant species, as the remnant habitats become smaller and more fragmented, it is vital to estimate the population spread rate of small patches in order to effectively manage and preserve them for potential future range expansion. However, population spread rate has rarely been quantified at the patch level to inform conservation strategies and management decisions. To close this gap, we quantify the patch-specific seed dispersal and local population dynamics of Minuartia smejkalii, which is a critically endangered plant species endemic in the Czech Republic and is of urgent conservation concern. Želivka and Hrnčíře, Czechia. We conducted demographic analyses using population projection matrices with long-term demographic data and used an analytic mechanistic dispersal model to simulate seed dispersal. We then used information on local population dynamics and seed dispersal to estimate the population spread rate and compared the relative contributions of seed dispersal and population growth rate to the population spread rate. We found that although both seed dispersal and population growth rate in M. smejkalii were critically limited, the population spread rate depended more strongly on the maximal dispersal distance than on the population growth rate. We recommend conservationists to largely increase the dispersal distance of M. smejkalii. Generally, efforts made to increase seed dispersal ability could largely raise efficiency and effectiveness of conservation actions for critically endangered plant species.


Cholestatic jaundice in neonates: How common is biliary atresia? Experience at an Australian tertiary centre.
To (i) review the aetiologies of neonatal cholestasis among term and preterm neonates at a single tertiary centre in Australia; (ii) identify clinical variables associated with biliary atresia (BA) and non-BA aetiology of neonatal cholestasis; (iii) investigate the utility of hepatobiliary scintigraphy in predicting BA among term and preterm neonates. A retrospective cohort study of neonates born and investigated for cholestasis at two co-located neonatal and children facilities from January 2013 to December 2017. Of the 139 neonates with cholestasis, BA and intestinal-failure-associated liver-disease was the most common cause of neonatal cholestasis in term (18%) and preterm (66%) cohorts, respectively. Incidence of BA was higher in term (1:6) than preterm (1:50) neonates (OR 10.29; 95% CI 2.06-49.97, P = 0.0024). Higher birthweight, acholic stool, absent or abnormal gallbladder on ultrasound was significantly associated with BA while gestational age ≤32 weeks, total parenteral nutrition ≥14 days and low albumin were associated with non-BA aetiology of cholestasis. In diagnosing BA, non-draining hepatobiliary scintigraphy demonstrated a lower specificity (73% vs. 90%) and lower positive predictive value (25% vs. 78%) in preterm compared to term neonates. Aetiology of cholestasis among preterm neonates differs from those in term neonates and currently existing diagnostic algorithm for neonatal cholestasis may need to be modified for preterm cohort, taking into account the prevalence for each aetiology, potential predictors and cost-efficiency.


2-deoxy-D-Glucose Synergizes with Doxorubicin or L-Buthionine Sulfoximine to Reduce Adhesion and Migration of Breast Cancer Cells.
Cancer metastasis depends on cell motility which is driven by cycles of actin polymerization and depolymerization. Reactive oxygen species (ROS) and metabolic oxidative stress have long been associated with cancer. ROS play a vital role in regulating actin dynamics that are sensitive to oxidative modification. The current work aimed at studying the effects of sub-lethal metabolic oxidative stress on actin cytoskeleton, focal adhesion and cell migration. T47D human breast cancer cells were treated with 2-deoxy- D-glucose (2DG), L-buthionine sulfoximine (BSO), or doxorubicin (DOX), individually or in combination, and changes in intracellular total glutathione and malondialdehyde (MDA) levels were measured. The expression of three major antioxidant enzymes was studied by immunoblotting, and cells were stained with fluorescent- phalloidin to evaluate changes in F-actin organization. In addition, cell adhesion and degradation ability were measured. Cell migration was studied using wound healing and transwell migration assays. Our results show that treating T47D human breast cancer cells with drug combinations (2DG/BSO, 2DG/DOX, or BSO/DOX) decreased intracellular total glutathione and increased oxidized glutathione, lipid peroxidation, and cytotoxicity. In addition, the drug combinations caused a reduction in cell area and mitotic index, prophase arrest and a decreased ability to form invadopodia. The formation of F-actin aggregates was increased in treated T47D cells. Moreover, combination therapy reduced cell adhesion and the rate of cell migration. Our results suggest that exposure of T47D breast cancer cells to combination therapy reduces cell migration via effects on metabolic oxidative stress.


Concomitant diabetes or hypertension with metabolic syndrome on the extent of intracranial atherosclerotic stenosis.
Intracranial atherosclerotic stenosis (ICAS) is a major cause of ischemic stroke, especially in Asia. Assessing relationships between novel risk factors and ICAS could lead strategies for improving outcomes. We aimed to evaluate the link between severity of metabolic syndrome (MetS) and extent of ICAS (≥ 50% stenosis). We conducted a cross-sectional study of consecutive Korean patients with acute ischemic stroke, admitted from March 2009 through May 2013, who underwent brain MRI/MRA. Patients were stratified into hypertension only, diabetes mellitus (DM), MetS only, MetS and hypertension, MetS and DM, and neither. MetS was defined using the harmonized criteria. Of 1220 patients (mean age, 68.2 ± 12.7; female, 42.6%), 238 had hypertension only, 67 DM, 48 MetS only, 311 MetS and hypertension, 403 MetS and DM (88.3% having concomitant hypertension), and 153 neither. Patients with MetS and DM had higher prevalence of ICAS and more ICAS lesions vs. those with neither (all P < 0.001). Compared with neither condition (1.3 ± 0.8), extent of MetS component were greater by increasing MetS severity category (1.7 ± 0.5, 1.8 ± 0.4, 3.3 ± 0.5, 3.4 ± 0.6, and 3.9 ± 0.7, P < 0.001). Odds of ICAS (OR 3.40, 95% CI, 1.82-6.36), ICAS (≥ 2) (4.65, 2.15-10.05), and ICAS (≥ 3) (2.82, 1.02-7.82) remained independently higher in patients with MetS and DM. DM, MetS only, or MetS and hypertension trended towards higher ICAS lesions. MetS and DM along with hypertension is associated with more extensive ICAS than MetS and hypertension or MetS only. Patients with MetS at high risk of hypertension and DM may benefit from therapeutic lifestyle changes to prevent stroke risk.


MRI of soft-tissue masses: the relationship between lesion size, depth, and diagnosis.
To identify the relationship between depth and size of soft-tissue mass lesions relative to histological diagnosis in a range of malignant neoplastic, benign neoplastic, and non-neoplastic conditions on magnetic resonance imaging (MRI). The MRI findings of 571 consecutive patients referred to a supra-regional orthopaedic oncology unit with a suspected soft-tissue neoplasm were reviewed and included in the study. The patient age, histological diagnosis, lesion size, anatomical location, and lesion depth (superficial or deep to fascia) were recorded. There were 288 males and 283 females (mean age 48 years, age range 2-92 years). The mean age was 54.1 years for malignant neoplastic lesions compared with 40.1 years for benign neoplastic and 45.4 years for non-neoplastic conditions. There was a significant age difference when malignant lesions were compared with benign neoplastic and non-neoplastic lesions (p<0.001). No significant relationship was present between lesion depth (480 deep, 91 superficial) and diagnosis (288 malignant neoplastic, 197 benign neoplastic and 86 non-neoplastic lesions). However, a significant relationship was identified between lesion size and diagnosis (p<0.001). Furthermore, a significant relationship was identified when lesion size greater than 5 cm, lesion depth, and diagnosis were analysed. Current guidelines suggest the most important variables for assessing risk of malignancy in a soft-tissue lesion include size, depth in relation to the fascia, increasing size, and pain. The current study suggests that relationship to fascia is less important as a predictor of malignant potential in a patient cohort treated at a supra-regional centre. Significant risk factors include increasing patient age and lesion size greater than or equal to 5 cm.


Social equity-based distribution networks design for the COVID-19 vaccine.
This study aims to investigate the role of social equity in vaccine distribution network design problems. Inspired by the current COVID-19 vaccine allocation in-country context, we capture social equity-based distribution by modeling three theories: Rawls' theory, Sadr's theory, and utilitarianism. We consider various social groups based on degree of urbanization, including inhabitants of cities, towns and suburbs, and rural areas. The distribution problem is subject to, on the one hand, demand-side uncertainty characterized by the daily contamination rate and its space-time propagation that anticipate the in-need population. On the other hand, supply-side uncertainty characterized by the stochastic arrival of vaccine doses for the supply period. To tackle this problem, we propose a novel bi-objective two-stage stochastic programming model using the sample average approximation (SAA) method. We also develop a lexicographic goal programming approach where the social equity objective is prioritized, thereafter reaching an efficiency level. Using publicly available data on COVID-19 in-country propagation and the case of two major provinces in Iran as example of middle-income country, we provide evidence of the benefits of considering social equity in a model-based decision-making approach. The findings suggest that the design solution produced by each social equity theory matches its essence in social science, differing considerably from the cost-based design solution. According to the general results, we can infer that each social equity theory has its own merits. Implementing Rawls' theory brings about a greater coverage percentage in rural areas, while utilitarianism results in a higher allocation of vaccine doses to social groups compared to the Sadr and Rawls theories. Finally, Sadr's theory outperforms Rawls' in terms of both the allocation and cost perspective. These insights would help decision-makers leverage the right equity approach in the COVID-19 vaccine context, and be better prepared for any pandemic crisis that the future may unfold.


Optical and electrical applications of ZnS(x)Se(1-x) nanowires-network with uniform and controllable stoichiometry.
Single crystalline ternary ZnS(x)Se(1-x) nanowires with uniform chemical stoichiometry and accurately controllable compositions (0≤x≤ 1) were synthesized through a simple and yet effective one-step approach with a specially designed modification. Energy-gap-tuning via compositional change was achieved for a direct band gap from 2.6 to 3.6 eV. Raman spectroscopy studies revealed typical two-mode behavior indicative of high miscibility in the alloyed compound. Moreover, the enhanced electrical-conductivity and gating effect behavior after the formation of ternary alloy enable their application in nano/micro-field effect transistor devices. In addition, the slow recombination rate in the photo-response process indicates their potential for photoelectric applications.


Physicochemical properties and antioxidant activities of acidic polysaccharides from wampee seeds.
Two novel polysaccharide fractions, named WP1 and WP3, were extracted and purified from wampee [Clausena lansium (Lour.) Skeels] seeds. Their physicochemical properties, in vitro and in vivo antioxidant activities were investigated. Results indicated that both WP1 and WP3 were acidic heteropolysaccharides with uronic acid content of 45.35% and 56.79%, respectively. The molar ratio of rhamnose, glucuronic acid, galacturonic acid, glucose, galactose, arabinose of WP1 was 5.01:1.50:39.53:1:10.76:23.50 while WP3 was 5.76:1.73:27.27:1:4.72:8.77. Furthermore, WP3 not only exhibited stronger in vitro antioxidant activities than WP1, but also more significantly increased the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) level in serum of SD rats induced by high-fat diet.


Encystment in Acanthamoeba castellanii: a review.
Differentiation of Acanthamoeba castellanii trophozoites involves massive turnover of cellular components and remodelling of organelle structure and function so as to produce a cryptobiotic cell, resistant to desiccation, heat, freezing, and chemical treatments. This review presents a summary of a decade of research on the most studied aspects of the biochemistry of this process, with emphasis on problems of biocide and drug resistances, putative new targets, molecular and cell biology of the process of encystment, and the characteristics of the encysted state. As well as the intrinsic pathogenicity of the organism towards the cornea, and the ability of related species to invade the human brain, its propensity for harbouring and transmitting pathogenic bacteria and viruses is considerable and leads to increasing concerns. The long-term survival and resistance of cysts to drugs and biocides adds another layer of complexity to the problem of their elimination.


Is Gleason Grade 5 Prostate Cancer Resistant to Conventional Androgen Deprivation Therapy?
Synthesis of data from randomized trials suggests that long-term versus short-term androgen deprivation therapy may be most effective in men with Gleason grade 4 prostate cancer (PCa) and less or ineffective in men with Gleason grade 5 PCa.


Voice Over Body? Older Adults' Reactions to Robot and Voice Assistant Facilitators of Group Conversation.
Intelligent agents have great potential as facilitators of group conversation among older adults. However, little is known about how to design agents for this purpose and user group, especially in terms of agent embodiment. To this end, we conducted a mixed methods study of older adults' reactions to voice and body in a group conversation facilitation agent. Two agent forms with the same underlying artificial intelligence (AI) and voice system were compared: a humanoid robot and a voice assistant. One preliminary study (total n = 24) and one experimental study comparing voice and body morphologies (n = 36) were conducted with older adults and an experienced human facilitator. Findings revealed that the artificiality of the agent, regardless of its form, was beneficial for the socially uncomfortable task of conversation facilitation. Even so, talkative personality types had a poorer experience with the "bodied" robot version. Design implications and supplementary reactions, especially to agent voice, are also discussed. The online version contains supplementary material available at 10.1007/s12369-022-00925-7.


Causes of Erythema Nodosum in Patients Admitted to a Tertiary Care Hospital in Spain.
Erythema nodosum (EN) is the most frequent panniculitis, and although it can be idiopathic, it presents multiple causal processes. We made a retrospective, observational and descriptive study about causes of EN in patients admitted to a third-level Spanish hospital over a period of 11 years, and we compared the results obtained with those published in other studies. We compared the analytical markers of inflammation between inflammatory and non-inflammatory causes of EN. The final cohort was composed by 52 patients, with 20% of idiopathic cases, 34% of cases secondary to infections and another 34% of cases secondary to autoimmune diseases. There were no cases secondary to drugs or lymphomas. We did not observe significant differences in the analytical parameters of inflammation between inflammatory or non-inflammatory cause of EN.


Glandular innovations for a tunnelling life: Silk and associated leg glands in Melissotarsus and Rhopalomastix queen and worker ants.
As in other Hymenoptera, adult ants cannot secrete silk, unlike the larvae that spin a cocoon prior to metamorphosis. Fisher and Robertson (1999) first showed the existence of a silk gland in the head of adult Melissotarsus beccarii workers, and we confirm this with detailed histology and ultrastructural comparisons of both queens and workers. This African genus exhibits extreme morphological adaptations (legs, head shape and mandibular muscles) for tunnelling behaviour inside living trees, that underlie an obligate mutualism with scale insects. Rhopalomastix is its sister genus distributed across Asia, and we show that queens and workers also have a silk gland. This lineage of minute workers relies on silk to secure their network of tunnels against other arboreal ants. We show striking differences between these genera in the anatomy and ultrastructure of the cells that secrete silk, especially numerous vacuoles and an unexpectedly branched end apparatus in Melissotarsus. Moreover, the legs of Melissotarsus are much more specialized for tunnelling, and this includes highly expanded basitarsi. The latter house the novel 'Delage-Darchen gland', and we document its anatomy and ultrastructure, suggesting a proteinaceous secretion to harden roofs made of silk combined with wood fragments. The restriction of the Delage-Darchen gland to Melissotarsus, combined with a modified silk gland (an almost three-fold increase in the number of secretory cells, and ultrastructural differences suggestive of higher secretory activity), are evidence of an outstanding evolutionary divergence relative to Rhopalomastix. Synthesis of silk by adults is a significant innovation among ants, but its augmented production in Melissotarsus makes them better adapted for the hazards of arboreal life.


Low (0-5) Alberta Stroke Program Early Computed Tomography Score on admission predictive of worse functional outcome after mechanical thrombectomy for anterior circulation large vessel occlusion.
We examined functional outcomes of mechanical thrombectomy (MT) procedures following anterior circulation large vessel occlusion (ACLVO)-related acute ischemic strokes (AIS). Results were based on admission non-contrast computed tomography (NCCT) studies, using the Alberta Stroke Program Early Computed Tomography Score (ASPECTS) as standard metric. Qualifying subjects were consecutive patients (N = 343) at a single center undergoing MT for ACLVO-related AIS. Each was grouped according to ASPECTS status on admission, determined from NCCT images by two physicians. Primary clinical endpoint was functional independence, assessed via modified Rankin Scale (mRS) at 90 days. Secondary endpoints were vessel recanalization (i.e., modified Thrombolysis in Cerebral Infarction [mTICI] score), symptomatic intracranial hemorrhage (sICH), and mortality. In this study population (mean age, 63.6 ± 12.6 years; women, 30.3%; median baseline National Institute of Health Stroke Scale [NIHSS] score, 15.2 ± 4.5), patients were stratified by ASPECTS tier at presentation, either 0-5 (n = 50) or 6-10 (n = 293). Multivariate logistic regression showed a relation between ASPECTS values ≤ 5 and lesser chance of 90-day functional improvement (OR = 2.309, 95% confidence interval [CI] 1.012-5.271; p = 0.047), once adjusted for age, baseline NIHSS score, diabetes mellitus, HbA1c concentration, D-dimer level, occlusive location, numbers of device passes, and successful recanalization. ASPECTS values ≤ 5 correspond with worse long-term functional improvement (mRS scores > 2) in patients undergoing MT for ACLVO-related AIS. Other independent determinants of functional outcomes after MT are age, baseline NIHSS score, HbA1c concentration, and successful recanalization.


Innovation policy and ecological welfare performance: evidence from a quasi-natural experiment of China.
The National Innovative City Pilot Policy (NICPP) is a policy implemented by the Chinese government to create an environment conducive to innovation, optimize industrial structure, promote economic development, and stimulate green innovation. The impact of this policy on ecological welfare performance is a question worth exploring. Based on panel data from 285 cities from 2007 to 2021, this paper uses the multi-period difference-in-difference (DID) model, propensity score matching method, and spatial DID model to study the impact of NICPP on ecological welfare performance and spatial spillover effects. The results show that (1) NICPP can significantly improve ecological welfare performance. (2) The mechanism analysis found that NICPP mainly improves ecological welfare performance through technological innovation investment, industrial structure upgrading, and increasing government attention. (3) The heterogeneity analysis found that NICPP has a more substantial driving effect on the ecological welfare development of cities in the eastern and western regions, cities with higher administrative levels, and cities with lower secondary industry agglomeration. (4) Further research has found that NICPP not only promotes the development of local ecological welfare but also has a positive spatial spillover effect on the ecological welfare performance of neighboring regions. This paper enriches the research on the effects of NICPP and provides policy references for the sustainable development of cities.


Compatibility study between ibuproxam and pharmaceutical excipients using differential scanning calorimetry, hot-stage microscopy and scanning electron microscopy.
Differential scanning calorimetry (DSC) was used as a screening technique for assessing the compatibility of ibuproxam with some currently employed pharmaceutical excipients. The influence of processing effects (simple blending, cogrinding or kneading) on drug stability was also evaluated. On the basis of DSC results, ibuproxam was found to be compatible with corn starch, avicel and sodium carboxymethylcellulose. Some drug-excipient interaction was observed with polyethyleneglycol 4000, palmitic acid, stearic acid, Ca and Mg stearate. Actual solid-phase interactions of the drug with polyvinylpolypyrrolidone and polyvinylpirrolidone K30 were induced by mechanical treatments. Hot-stage microscopy (HSM) and scanning electron microscopy (SEM) were of help in interpreting the DSC results and excluding in all cases relevant pharmaceutical incompatibilities.


Histopathology of the subretinal fibrosis and uveitis syndrome.
A chorioretinal biopsy was obtained from a patient with subretinal fibrosis and chronic uveitis. The biopsy specimen was analyzed by conventional light and electron microscopy and by immunohistochemical methods. These demonstrated a markedly inflamed choroid with a predominance of B cells and plasma cells. Complement and IgG were deposited above Bruch's membrane. The subretinal fibrosis tissue contained islands of cells with retinal pigment epithelial characteristics; however, some of these cells demonstrated surface determinants of Müller cells. There were no circulating antiretinal antibodies detected nor could virus be cultured from the biopsy specimen. The clinical appearance of this entity is distinctive and consists of a chronic posterior uveitis with transient initial yellow-white deep retinal lesions and the later development of large white subretinal fibrotic areas. The EOG is markedly decreased. We hypothesize that the immunologic events involved in this entity include antibody production with immunoglobulin and complement deposition leading to retinal and retinal pigment epithelial destruction and a subretinal fibrous proliferation.


Influence of Flagellin Polymorphisms, Gene Regulation, and Responsive Memory on the Motility of Xanthomonas Species That Cause Bacterial Spot Disease of Solanaceous Plants.
Increasingly, new evidence has demonstrated variability in the epitope regions of bacterial flagellin, including in regions harboring the microbe-associated molecular patterns flg22 and flgII-28 that are recognized by the pattern recognition receptors FLS2 and FLS3, respectively. Additionally, because bacterial motility is known to contribute to pathogen virulence and chemotaxis, reductions in or loss of motility can significantly reduce bacterial fitness. In this study, we determined that variations in flg22 and flgII-28 epitopes allow some but not all Xanthomonas spp. to evade both FLS2- and FLS3-mediated oxidative burst responses. We observed variation in the motility for many isolates, regardless of their flagellin sequence. Instead, we determined that past growth conditions may have a significant impact on the motility status of isolates, because we could minimize this variability by inducing motility using chemoattractant assays. Additionally, motility could be significantly suppressed under nutrient-limited conditions, and bacteria could "remember" its prior motility status after storage at ultracold temperatures. Finally, we observed larger bacterial populations of strains with flagellin variants predicted not to be recognized by either FLS2 or FLS3, suggesting that these bacteria can evade flagellin recognition in tomato plants. Although some flagellin variants may impart altered motility and differential recognition by the host immune system, external growth parameters and gene expression regulation appear to have more significant impacts on the motility phenotypes for these Xanthomonas spp.[Formula: see text] Copyright © 2022 The Author(s). This is an open access article distributed under the CC BY 4.0 International license.


Automated contrast medium monitoring system for computed tomography--Intra-institutional audit.
The aim of this study was to analyze the usage and the data recorded by a RIS-PACS-connected contrast medium (CM) monitoring system (Certegra(®), Bayer Healthcare, Leverkusen, Germany) over 19 months of CT activity. The system used was connected to two dual syringe power injectors (each associated with a 16-row and a high definition 64-row multidetector CT scanner, respectively), allowing to manage contrast medium injection parameters and to send and retrieve CT study-related information via RIS/PACS for any scheduled contrast-enhanced CT examination. The system can handle up to 64 variables and can be accessed via touchscreen by CT operators as well as via a web interface by registered users with three different hierarchy levels. Data related to CM injection parameters (i.e. iodine concentration, volume and flow rate of CM, iodine delivery rate and iodine dose, CM injection pressure, and volume and flow rate of saline), patient weight and height, and type of CT study over a testing period spanning from 1 June 2013 to 10 January 2015 were retrieved from the system. Technical alerts occurred for each injection event (such as system disarm due to technical failure, disarm due to operator's stop, incomplete filling of patient data fields, or excessively high injection pressure), as well as interoperability issues related to data sending and receiving to/from the RIS/PACS were also recorded. During the testing period, the CM monitoring system generated a total of 8609 reports, of which 7629 relative to successful injection events (88.6%). 331 alerts were generated, of which 40 resulted in injection interruption and 291 in CM flow rate limitation due to excessively high injection pressure (>325 psi). Average CM volume and flow rate were 93.73 ± 17.58 mL and 3.53 ± 0.89 mL/s, and contrast injection pressure ranged between 5 and 167 psi. A statistically significant correlation was found between iodine concentration and peak IDR (rs=0.2744, p<0.0001), as well as between iodine concentration and iodine dose (rs=0.3862, p<0.0001) for all CT studies. Automated contrast management systems can provide a full report of contrast use with the possibility to systematically compare different contrast injection protocols, minimize errors, and optimize organ-specific contrast enhancement for any given patient and clinical application. This can be useful to improve and harmonize the quality and consistency of contrast CT procedures within the same radiological department and across the hospital, as well as to monitor potential adverse events and overall costs.


Automated flow fluorescent immunoassay for part per trillion detection of the neonicotinoid insecticide thiamethoxam.
An ultra sensitive automated flow fluorescent immunoassay was developed using the KinExAtrade mark 3000 system for quantitative analysis of the neonicotinoid insecticide thiamethoxam. Five new monoclonal antibodies were obtained and screened with a competitive ELISA. One monoclonal antibody designated as E6VI was evaluated for sensitivity, selectivity and solvent tolerance with the KinExA. Sensitivity determined from the concentration of half-maximal inhibition (IC50) was obtained by plotting KinExA signals to a four-parameter sigmoidal curve as a function of analyte concentrations. For the most sensitive clone, the IC50 and the limit of detection were approximately 30 pg ml(-1) and 16 pg ml(-1), respectively. Cross-reactivity was estimated by measuring the equilibrium constants (K(d)) for four other neonicotinoid insecticides (clothianidin, imidacloprid, dinotefuran, and acetamiprid). E6VI was very specific to thiamethoxam with <0.11% cross-reactivity for tested neonicotinoids. An excellent correlation (r2=0.99) was obtained between spiked and measured concentrations of thiamethoxam in stream and tap water, potato, cucumber, and apple samples.


Relationship between Acculturative Stress and Pain Catastrophizing in Korean Americans.
Acculturative stress is speculated to be a sociocultural factor contributing to pain since cultural beliefs and practices can influence the way patients perceive and respond to pain. However, the relationship between acculturative stress and pain catastrophizing remains poorly understood. Therefore, we examined the relationship between acculturative stress and pain catastrophizing in Korean Americans. We collected survey data from Korean American in Texas (N = 374). Acculturative stress was measured with the Acculturative Stress Scale, and pain catastrophizing was measured with the Pain Catastrophizing Scale. Participants' mean age was 46.89 years, and 63% were women. Bivariate and multivariate statistical analyses indicated that higher acculturative stress may contribute to higher pain catastrophizing (regression coefficient = 1.02, P = 0.04). These findings advance our understanding of sociocultural factors associated with pain in Korean Americans; additional research with a larger sample is warranted for cross-validation.


Pilomatrix carcinoma of the vulva.
Pilomatrix carcinomas are rare, frequently occurring in older male patients. We report a case of vulvar pilomatrix carcinoma in a 30-year-old woman, the second known reported case occurring on the external genitalia. A 30-year-old female originally presented at an outside institution for the management of an asymptomatic vulvar mass that was biopsied and read as invasive squamous cell carcinoma. Pathology review at our institution reclassified the vulvar mass as a low-grade pilomatrix carcinoma. The patient underwent radical hemivulvectomy without an inguinal-femoral groin node dissection. She has remained without evidence of disease recurrence for more than 5 years since her diagnosis. Pilomatrix carcinoma can be confused for an invasive squamous cell carcinoma. Due to its low risk of metastases, a less radical surgical approach can be taken. Consideration of this unusual malignancy is important in the determination of appropriate management.


Buffer therapy during out-of-hospital cardiopulmonary resuscitation.
The effects of infusing a buffer solution on resuscitability and outcome was tested in patients during out-of-hospital cardiac arrest. A number (502) of adults with asystole or ventricular fibrillation with failure of first defibrillation attempt were entered into a prospective, randomized, double-blind, controlled trial. Of these, 245 patients received 250 ml of sodium bicarbonate-trometamol- phosphate mixture with buffering capacity 500 mmol/l and 257 patients received 250 ml 0.9% saline. Except for the investigational infusion, all patients were resuscitated according to international guidelines. Eighty-seven patients (36%) receiving buffer were admitted to hospital ICU and 24 (10%) were discharged from hospital alive, vs. 92 (36%) and 35 (14%) receiving saline (95% confidence interval (CI) for difference between groups: -6%-6% for rate of admission and -1%-9% for rate of discharge). Using a logistic regression analysis, ventricular fibrillation as initial rhythm (odds ratio 8.06, CI 3.70-17.56) improved the outcome, whereas buffer therapy had no effect (odds ratio 0.77, CI 0.43-1.41). Mean base excess at hospital admission was -9 after Tribonat vs. -11 after saline (P = 0.04, CI for difference 0.2-3.8). Only 16 of the 502 patients had arterial alkalosis on arrival in the hospital and no patient had a positive base excess. Patients resuscitated after out-of-hospital cardiac arrest had metabolic acidosis, but buffer therapy did not improve the outcome.


Immune-mediated polyneuropathy in cats: Clinical description, electrodiagnostic assessment, and treatment.
Suspected immune-mediated polyneuropathy has been increasingly reported in cats, especially in the last decade, but the condition remains poorly understood. Refine the clinical description and review the classification of this condition based on electrodiagnostic investigation and evaluate the benefit of corticosteroid treatment and L-carnitine supplementation. Fifty-five cats presented with signs of muscular weakness and electrodiagnostic findings consistent with polyneuropathy of unknown origin. Retrospective, multicenter study. Data from the medical records were reviewed. The owners were contacted by phone for follow-up at the time of the study. The male-to-female ratio was 2.2. The median age of onset was 10 months, with 91% of affected cats being <3 years of age. Fourteen breeds were represented in the study. The electrodiagnostic findings supported purely motor axonal polyneuropathy. Histological findings from nerve biopsies were consistent with immune-mediated neuropathy in 87% of the tested cats. The overall prognosis for recovery was good to excellent, as all but 1 cat achieved clinical recovery, with 12% having mild sequelae and 28% having multiple episodes during their lifetime. The outcome was similar in cats with no treatment when compared with cats receiving corticosteroids or L-carnitine supplementation. Immune-mediated motor axonal polyneuropathy should be considered in young cats with muscle weakness. This condition may be similar to acute motor axonal neuropathy in Guillain-Barré syndrome patients. Based on our results, diagnostic criteria have been proposed.


The Israel National Bariatric Surgery Registry: the inception process.
Obesity rates in Israel are increasing, and so is the popularity of bariatric surgeries, which reached in 2017 a prevalence rate of 1428.7 surgeries per million citizens. However, data regarding patient characteristics and surgery outcomes, including complications, are limited and the procedure requires monitoring. To establish a national bariatric surgery registry with high reliability and validity. All private and public medical centers performing bariatric surgeries in the state of Israel. The Israeli Bariatric Surgery Registry (IBSR) was established in June 2013 by the Israel Center for Disease Control in the Ministry of Health, in collaboration with the Israel Bariatric Surgery Society. An official directive of the Director General of the Ministry of Health as of 2013 made reporting of all bariatric surgeries carried out in Israel mandatory. The bariatric surgery centers relay clinical and surgical information to the IBSR. Presurgery and follow-up outcome information was retrieved from all 4 health maintenance organizations. All 32 certified bariatric units report to the national IBSR. National reporting rates increased from 46.3% in 2013 to 98.7% in 2017. Adherence to bariatric surgery guidelines also increased from 72.8% in 2013 to 98.7% in 2017, and fewer patients not fulfilling the guidelines underwent bariatric surgeries in 2017. Importantly, the considerable annual preregistry increase in surgical procedures has been halted. Registry data regarding obesity-related co-morbidities were validated against hospital files with high Cohen's kappa coefficients for hypertension (r = .8), diabetes (r = .8), and sleep apnea (r = .7). The national IBSR is an identified, validated, mandatory database with access to other national databases, which enables quality assurance of bariatric surgeries in Israel and short- and long-term postoperative follow-up.


Hydra gasdermin-gated pyroptosis signalling regulates tissue regeneration.
Pyroptosis, an inflammatory form of programmed cell death, is directly executed by gasdermin (GSDM) depending on its N-terminal pore-forming fragment-mediated membrane-disrupting, triggering intracellular contents release, which plays important roles in mammalian anti-infection and anti-tumor immune responses. However, whether pyroptosis engages in the regulation of tissue regeneration remains largely unknown. Here, utilizing Hydra vulgaris as the research model, we found that an HyCARD2-HyGSDME-mediated pyroptosis signalling is activated in both head and foot regenerated tips after amputation. Impeding pyroptosis by knocking down the expression of either HyGSDME or HyCARD2 significantly hampered both head and foot regeneration in Hydra. Mechanistically, the activation of HyCARD2-HyGSDME axis at wound sites is dependent of intracellular mitochondrial reactive oxygen species (mtROS), the removing of which hindered Hydra head regeneration. Moreover, the HyCARD2-HyGSDME axis-gated pyroptosis was found to enhance the initial secretion and upregulated expression of Wnt3. Collectively, these findings indicate that gasdermin-gated pyroptosis is critical for the evoking of Wnt signalling to facilitate Hydra tissue regeneration, which provides insights into functional diversification within the gasdermin family in the animal kingdom.


Left Profunda Femoral Artery Pseudoaneurysm After Revision Total Hip Arthroplasty.
We present a case report of an 84-year-old male who presented with a profunda femoris artery (PFA) pseudoaneurysm 8 years after the index revision total hip arthroplasty procedure. Failure of revision hardware and subsequent migration of implants led to damage of the PFA and pseudoaneurysm formation. The patient was hemodynamically unstable on presentation and required emergent endovascular intervention. Once medically stabilized, the patient underwent extensive debridement of the aneurysm and hematoma bed and broken hardware was removed to prevent further complications. At 6-month follow-up, the patient was able to mobilize independently and had returned to all prior levels of activities of daily living. We discuss the vascular anatomy of the hip, the paucity of literature on PFA pseudoaneurysm, as well as the likely etiology of total hip arthroplasty failures.


Evaluating the effect of regulatory prohibitions against risk selection by health status on supplemental insurance ownership in Israel.
In Israel, supplemental insurance, which covers services not included in the mandatory basic benefits package, is offered by sick funds and regulated by the Ministry of Health. In 1998, policy regulations were set to eliminate barriers that prevented the ill from purchasing supplemental insurance, thereby increasing equality and risk solidarity. In this paper, we examine whether these regulations have indeed changed the extent of ownership and characteristics of policyholders, using data from surveys conducted in 1995, 1997, 1999, and 2001. The findings indicate that while there were no significant changes between 1995 and 1997, there was a significant increase in ownership among those with poor health status after the new regulations came into effect. We conclude that administrative regulations can influence the structure of supplemental insurance to achieve desired social values, and discuss additional policy options that are currently under debate in Israel to further promote equality and solidarity in this market by increasing accessibility to low income and other underserved populations.


Component-resolved diagnostics can be useful for identifying hazelnut allergy in Japanese children.
Cor a 9 and Cor a 14 are effective markers for predicting hazelnut allergy. However, there have been no reports on the component-resolved diagnostics (CRD) of hazelnut allergy using an oral food challenge (OFC) for diagnosis in Asia. We hypothesized that CRD would improve the accuracy of diagnosing hazelnut allergies in Japanese children. We recruited 91 subjects (median age: 7.3 years) who were sensitized to hazelnuts and had performed a hazelnut OFC at the National Hospital Organization Sagamihara National Hospital between 2006 and 2017. All subjects were classified as allergic or asymptomatic to 3 g of hazelnuts. The sIgE levels (hazelnut/Cor a 1/Cor a 8/Cor a 9/Cor a 14/alder pollen) were measured using ImmunoCAP. We aimed to determine the predictive factors of hazelnut allergy. Nine subjects (10%) were allergic to ≤3 g of hazelnuts. Levels of sIgE for Cor a 9 in hazelnut-allergic subjects were significantly higher than those in asymptomatic subjects (4.47 vs. 0.76 kUA/L, p = 0.039). Levels of sIgE to alder pollen and Cor a 1 in hazelnut-allergic subjects were significantly lower than those in asymptomatic subjects (<0.10 vs 13.0 kUA/L, p = 0.004; <0.10 vs 5.03 kUA/L, p = 0.025). The area under the receiver operating characteristics curve for hazelnut/alder/Cor a 1/Cor a 9 was 0.55/0.78/0.72/0.71, respectively, with p = 0.651/0.006/0.029/0.040, respectively. The findings of a high sIgE level for Cor a 9 and a low sIgE level for Cor a 1 can improve the diagnostic accuracy to better identify Japanese children sensitized to hazelnuts.


Targeted misexpression of NAC052, acting in H3K4 demethylation, alters leaf morphological and anatomical traits in Arabidopsis thaliana.
In an effort to identify genetic regulators for the cell ontogeny around the veins in Arabidopsis thaliana leaves, an activation-tagged mutant line with altered leaf morphology and altered bundle sheath anatomy was characterized. This mutant had a small rosette area with wrinkled leaves and chlorotic leaf edges, as well as enhanced chloroplast numbers in the (pre-)bundle sheath tissue. It had a bundle-specific promoter from the gene GLYCINE DECARBOXYLASE SUBUNIT-T from the C4 species Flaveria trinervia (GLDTFt promoter) inserted in the coding region of the transcriptional repressor NAC052, functioning in H3K4 demethylation, in front of an alternative start codon in-frame with the natural start codon. Reconstruction of the mutation event of our activation-tagged line by creating a line expressing an N-terminally truncated sequence of NAC052 under control of the GLDTFt promoter confirmed the involvement of NAC052 in leaf development. Our study not only reveals leaf anatomic and transcriptomic effects of an N-terminally truncated NAC052 under control of the GLDTFt promoter, but also identifies NAC052 as a novel genetic regulator of leaf development.


Determining Protease Substrates Within a Complex Protein Background Using the PROtein TOpography and Migration Analysis Platform (PROTOMAP).
The PROtein TOpography and Migration Analysis Platform (PROTOMAP) approach is a degradomics technique used to determine protease substrates within complex protein backgrounds. The method involves protein separation according to protein relative mobility, using sodium dodecyl sulfate polyacrylamide gel electrophoresis. Gel lanes are then sliced into horizontal sections, and in-gel trypsin digestion performed for each gel slice. Extracted peptides and corresponding proteins are identified using liquid chromatography-tandem mass spectrometry and bioinformatics. Results are compiled in silico to generate a peptograph for every identified protein, being a pictorial representation of sodium dodecyl sulfate polyacrylamide gel electrophoresis. Proteins shown by their peptograph to have migrated further through the gel (i.e., to a lower gel slice) in the lane containing the active protease(s) of interest, as compared to the control, are deemed putative protease substrates. PROTOMAP has broad applicability to a range of experimental conditions and protein pools. Coupling this with its simple and robust methodology, the PROTOMAP approach has emerged as a valuable tool with which to determine protease substrates in complex systems.


Trafficking and stability of voltage-gated calcium channels.
Voltage-gated calcium channels are important mediators of calcium influx into electrically excitable cells. The amount of calcium entering through this family of channel proteins is not only determined by the functional properties of channels embedded in the plasma membrane but also by the numbers of channels that are expressed at the cell surface. The trafficking of channels is controlled by numerous processes, including co-assembly with ancillary calcium channel subunits, ubiquitin ligases, and interactions with other membrane proteins such as G protein coupled receptors. Here we provide an overview about the current state of knowledge of calcium channel trafficking to the cell membrane, and of the mechanisms regulating the stability and internalization of this important ion channel family.


Electronic Health Record Adoption - Maybe It's not about the Money: Physician Super-Users, Electronic Health Records and Patient Care.
The slow adoption of electronic health record (EHR) systems has been linked to physician resistance to change and the expense of EHR adoption. This qualitative study was conducted to evaluate benefits, and clarify limitations of two mature, robust, comprehensive EHR Systems by tech-savvy physicians where resistance and expense are not at issue. Two EHR systems were examined - the paperless VistA / Computerized Patient Record System used at the Veterans' Administration, and the General Electric Centricity Enterprise system used at an academic medical center. A series of interviews was conducted with 20 EHR-savvy multiinstitutional internal medicine (IM) faculty and house staff. Grounded theory was used to analyze the transcribed data and build themes. The relevance and importance of themes were constructed by examining their frequency, convergence, and intensity. Despite eliminating resistance to both adoption and technology as drivers of acceptance, these two robust EHR's are still viewed as having an adverse impact on two aspects of patient care, physician workflow and team communication. Both EHR's had perceived strengths but also significant limitations and neither were able to satisfactorily address all of the physicians' needs. Difficulties related to physician acceptance reflect real concerns about EHR impact on patient care. Physicians are optimistic about the future benefits of EHR systems, but are frustrated with the non-intuitive interfaces and cumbersome data searches of existing EHRs.


Simvastatin therapy normalizes sympathetic neural control in experimental heart failure: roles of angiotensin II type 1 receptors and NAD(P)H oxidase.
In a previous study, we showed that simvastatin (SIM) therapy normalized sympathetic outflow and cardiovascular reflex regulation in chronic heart failure (CHF). However, the precise neural and cellular pathways for these effects are unknown. We hypothesized that SIM exerts its beneficial effect on autonomic function in CHF by downregulating central angiotensin II (Ang II) and superoxide mechanisms. Experiments were carried out on 36 male New Zealand White rabbits, 13 normal and 23 CHF. All rabbits were identically instrumented to record mean arterial pressure, heart rate, and renal sympathetic nerve activity (RSNA). Echocardiography was used to monitor cardiac function. Reverse transcription-polymerase chain reaction, Western blotting, and lucigenin-enhanced chemiluminescence were used to measure gene expression of Ang II type 1 receptor and NAD(P)H oxidase subunits and NAD(P)H oxidase activity in the rostral ventrolateral medulla. Compared with the CHF control group, SIM significantly reduced the central Ang II-induced pressor and sympathoexcitatory responses, decreased baseline RSNA (57.3+/-3.2% to 22.4+/-2.1% of maximum, P<0.05), increased baroreflex control of heart rate (gain(max), 1.6+/-0.3 to 4.5+/-0.2 bpm/mm Hg, P<0.05), and increased RSNA (gain(max), 1.7+/-0.2% to 4.9+/-0.6% of maximum/mm Hg, P<0.01). Importantly, SIM improved left ventricular function (EF, 32.4+/-4.1% to 51.7+/-3.2%, P<0.05). SIM also downregulated mRNA and protein expression of Ang II type 1 receptor and NAD(P)H oxidase subunits and inhibited NAD(P)H oxidase activity in the rostral ventrolateral medulla of CHF rabbits. Chronic intracerebroventricular infusion of Ang II completely abolished the aforementioned effects of SIM in CHF rabbits. These data strongly suggest that SIM normalizes autonomic function in CHF by inhibiting central Ang II mechanisms and therefore the superoxide pathway. These data also demonstrate that SIM improves left ventricular function in pacing-induced CHF rabbits.


The morphology of the sex pheromone gland in Drosophila grimshawi.
The morphology of a sex pheromone-producing gland found in the abdomen of Drosophila grimshawi males was studied by light and electron microscopy. This gland, consisting of two intra-anal lobes, contains cells that resemble those of other insect pheromone glands. However, in contrast to many other insect pheromone glands that release pheromone through the cuticle, cells of the intra-anal lobes secrete into a canaliculi-duct system that empties into the anal region. The liquid secretory product flows along the surface of the intra-anal lobes and is brushed onto the substrate by fingerlike projections on the lobes' surfaces.


A kinetic model of carnosine synthesis in human skeletal muscle.
Drawing on previously published data, a mathematical model is proposed to describe the synthesis of carnosine in muscle using a slow release β-alanine supplement (SR-CarnoSyn®). The model pre-supposes that the rate of synthesis for any given dose of β-alanine (within the range 1.6-6.4 g day-1) is constant with time, but is first order with respect to daily β-alanine dose. Simultaneously with synthesis, decay in carnosine is also assumed to be occurring, the rate in this case being a function of the concentration of carnosine. Decay in carnosine appears describable by first-order kinetics. By integration of the two rate reactions, a single mathematical equation was derived to describe the synthesis of carnosine and which closely fitted the experimental data over 56 days. The model, if validated by additional studies, could be used to compliment empirical observations of the changes in carnosine in muscle with supplementation, and allow objective examination of a number of possible influences affecting the rate constants of synthesis and decay.


Crystal structure of the arginine repressor protein in complex with the DNA operator from Mycobacterium tuberculosis.
The arginine repressor (ArgR) from Mycobacterium tuberculosis (Mtb) is a gene product encoded by the open reading frame Rv1657. It regulates the L-arginine concentration in cells by interacting with ARG boxes in the promoter regions of the arginine biosynthesis and catabolism operons. Here we present a 2.5-A structure of MtbArgR in complex with a 16-bp DNA operator in the absence of arginine. A biological trimer of the protein-DNA complex is formed via the crystallographic 3-fold symmetry axis. The N-terminal domain of MtbArgR has a winged helix-turn-helix motif that binds to the major groove of the DNA. This structure shows that, in the absence of arginine, the ArgR trimer can bind three ARG box half-sites. It also reveals the structure of the whole MtbArgR molecule itself containing both N-terminal and C-terminal domains.


Age-related changes in the proportion of types I and III collagen.
Previous studies of the age-related changes in interstitial collagens, have suggested that the proportion of type III collagen compared with type I decreases with age. In this study collagen concentration and the proportion of types were measured in heart, lung and skin of male Lewis rats aged between 1 day and 2 years. Collagen concentration, based on hydroxyproline levels, increased in all tissues up until 6 months of age, thereafter it increased in heart and lung, yet decreased in skin. The relative proportions of types I and III collagen were assessed after cyanogen bromide digestion of the tissue and separation of the resultant peptides by sodium dodecyl sulphate polyacrylamide gel electrophoresis. At 2 weeks of age collagen type III represented about one-third of types I and III in all tissues. After this age the proportion of type III increased up to 1 year in both heart (53.9 +/- 1.8%) and lung (47.7 +/- 2.8%), whereas it decreased in skin (18.6 +/- 1.5%). These data show that there are age-related changes in both collagen concentration and the relative proportions of types I and III collagen, but that the direction of these changes differs between tissues.


Multilayer rat hepatocyte aggregates formed on expanded polytetrafluoroethylene surface.
Feasibility of using a macroporous membrane material, expanded polytetrafluoroethylene (ePTFE), for culturing hepatocytes on its surface was examined. Adult rat hepatocytes were attached to an ePTFE surface and cultured in a hormonally defined medium supplemented with or without fetal calf serum (FCS, 10%) or bovine serum albumin (BSA, 0.03-3%). When cultured in a FCS-suplemented medium, hepatocytes reorganized themselves into multilayer cell aggregates on an ePTFE surface. The morphological characteristics of hepatocytes were influenced by the modification of the ePTFE surface as well as the culture medium. Hepatocytes cultured on a polyvinylalcohol (PVA)-coated ePTFE surface formed many more multilayer cell aggregates than those cultured on an uncoated ePTFE surface. Such highly multilayered hepatocyte aggregates were also noted when the cells were cultivated in a BSA-supplemented medium. On the other hand, when cultured in a FCS- or BSA-free medium, hepatocytes formed cell monolayers on both PVA-coated and uncoated ePTFE surfaces as did the cells on a collagen-coated polystyrene surface. The hepatocytes in the aggregates exhibited high albumin expression capability and low DNA synthesis rate as compared with those in monolayer cultures. The multilayer hepatocyte aggregates, as immobilized on a PVA-coated ePTFE surface in a serum-supplemented medium, are shown to be not only morphologically, but functionally differentiated, and will provide us a model system for the development of a bioreactor using hepatocytes, particularly for a hybrid-type artificial liver.


Accuracy of a SET of Screening Parameters Developed for the Diagnosis of Arterial Gas Embolism: The SANDHOG Criteria.
Arterial gas embolism (AGE) is a major cause of morbidity and mortality in self-contained underwater breathing apparatus (SCUBA) diving and certain medical procedures. There are currently no well-defined criteria to diagnose AGE. Emergency physicians often find themselves facing a decision whether or not a patient with dive-related symptoms has an AGE and needs to be transferred to a hyperbaric facility. The objective of this study was to test the accuracy of diagnostic criteria developed by the San Diego Hyperbaric Oxygen Group (SANDHOG) for the diagnosis of AGE. This was a retrospective review of consultations completed by the Hyperbaric Medicine Department (HBO) at the University of California San Diego where the diagnosis of AGE was considered. HBO staff blinded to the purpose of the study identified potential cases of AGE. The criterion standard was the final diagnosis by a panel of HBO specialists also blinded to the purpose of this study. Descriptive statistics and comparisons evaluating SANDHOG criteria compared to the criterion standard were performed. Twenty-six patients were identified for inclusion. Twenty-three of 26 (88%) were SCUBA divers, 2 had intravascular gas injections, and 1 patient had a military training chamber accident. Nineteen of 26 (73%) patients were diagnosed with AGE. A SANDHOG score of 2 had 94.7% sensitivity (95% confidence interval [CI] 71.9-99.7), 85.7% specificity (95% CI 42.0-99.2), positive likelihood ratio of 6.6 (95% CI 1.1-40.8), and negative likelihood ratio of 0.06 (95% CI 0.01-0.43) for AGE. A SANDHOG score <2 had a negative predictive value of 100% for AGE. The SANDHOG criteria appear to be reliable in diagnosing AGE. AGE is unlikely with SANDHOG scores <2, whereas SANDHOG scores ≥2 resulted in high sensitivity and specificity for AGE. Emergency physicians may find this tool useful in evaluating patients for suspected AGE, and it may assist in determining whether to transfer the patient to a hyperbaric facility. Future studies should be performed to further examine and validate the accuracy and inter-rater reliability of this tool.


Dietary and weight control practices among persons with hypertension: findings from the 1986 Behavioral Risk Factor Surveys.
The National Heart, Lung, and Blood Institute has concluded that reducing sodium intake, controlling weight, and moderating alcohol consumption can help patients with hypertension control their blood pressure. To determine whether such patients have adopted recommended dietary practices, we analyzed data collected in 1986 from telephone surveys of adults in 26 states (no. = 34,395). The self-reported dietary practices that we evaluated were: use of table salt, alcohol consumption, and weight control practices. In comparison with persons who did not have hypertension (no. = 26,848), those with hypertension who were receiving pharmacological therapy ("treated hypertensives," no. = 5,025) were more likely to report limiting their use of table salt (odds ratio [OR] = 2.5) and were less likely to have their weight controlled (OR = 0.4). Although overweight persons with hypertension were more likely than persons with normal blood pressure to attempt to lose weight, most have not included exercise in their weight loss efforts. There was no difference between persons who do not have hypertension and treated patients with hypertension in their use of alcohol. Untreated persons with hypertension (no. = 2,378) were less likely to limit their use of table salt and less likely to moderate their use of alcohol than treated persons with hypertension but otherwise reported similar dietary practices. Dietetic practitioners may need to emphasize moderation of alcohol use and the use of physical activity to lose weight when counseling patients with hypertension.


A note on factor normalization for deep neural network models.
Deep neural network (DNN) models often involve high-dimensional features. In most cases, these high-dimensional features can be decomposed into two parts: a low-dimensional factor and residual features with much-reduced variability and inter-feature correlation. This decomposition has several interesting theoretical implications for DNN training. Based on these implications, we develop a novel factor normalization method for better performance. The proposed method leads to a new deep learning model with two important characteristics. First, it allows factor-related feature extraction, and second, it allows for adaptive learning rates for factors and residuals. These model features improve the convergence speed on both training and testing datasets. Multiple empirical experiments are presented to demonstrate the model's superior performance.


Microbiological contamination of reindeer carcass during slaughter.
Microbiological counts for 10 different sampling sites of 28 reindeer carcasses were studied in 3 reindeer slaughterhouses in Finland. On each carcass the hindshank, round, abdomen, flank, brisket, foreleg, shoulder, neck, foreback and back were sampled immediately after slaughter, using a non-destructive swabbing method. The overall mean bacterial count for 10 sampling sites of reindeer carcasses was 1.51 +/- 0.51 log10 cfu/cm. Statistically significant differences were detected between sampling sites. The back part of the reindeer carcass, i.e. hindshank, round, back and foreback, seemed to be relatively clean. The most contaminated parts were the foreleg, brisket and abdomen (2.05-2.95 log10 cfu/cm2); these could be used for monitoring the hygiene of the reindeer carcass after slaughter. Differences between the 3 slaughterhouses were detected for some sampling sites, which may be due to differences in slaughter techniques and hygiene.


Idiopathic myelofibrosis with nodal, serosal and parenchymatous infiltration. Case report and review of the literature.
Idiopathic myelofibrosis (IMF) is a breakpoint cluster region rearrangement-negative chronic myeloproliferative disease with progressive bone marrow fibrosis. We report a female patient (65 years old) who was admitted to our hospital in 1996. Trephine bone marrow biopsy revealed diffuse fibrosis with atypical multilobulated megakaryocytes. A cellular phase of IMF was diagnosed. Three years later, despite being at intermediate risk, the patient developed generalized lymphadenopathy and multiple sclerosing tumors throughout the peritoneum and retroperitoneum. Biopsy specimens from these tumors revealed sclerosing hematopoietic infiltrates. The present case demonstrates that IMF not only can progress to acute leukemia but can also spread uncontrollably, or 'metastasize' with extensive sclerosing hematopoietic tumors throughout the body.


Community control of hypertension at the worksite in a metallurgical factory: results of 1-year follow-up.
This study was designed to assess advantages and cost-effectiveness of community control of hypertension at the worksite in a metallurgical factory in Pavia. Under consent of managers and trade-unionists, a screening program was undertaken. 2701 subjects (95% of the total number of employees) were screened: 277 (10.2%) were hypertensive, 101 (38%) did not know to be hypertensive, 56 (22%) knew to be hypertensive but they were untreated and only 20 (8%) of those under treatment were adequately treated. Of the 277 essential hypertensives, 262 (94%) adhered to the program. They were assigned to beta-blocking or diuretic treatment following WHO rules. Then an aggressive follow-up was started (the hypertensives were periodically called to control at the worksite). 257 (98%) were participants 1 year later. Our worksite hypertension control program allowed us to identify many cases of undiagnosed or untreated hypertension and to start an early treatment. One year after entry, the percentage of hypertensives achieving a normal blood pressure (85%) was almost twice as that obtained by conventional clinical approach employing the same type of treatment. Besides, more than 95% of hypertensives remained under control at 1 year. Regarding the costs, it is difficult to generalize, but our study suggests that, if there is the will, it is possible to realize programs of hypertension community control at a very low cost (in our experience: 43 dollars per hypertensive per year).


Functional inhibition of acid sphingomyelinase by Fluphenazine triggers hypoxia-specific tumor cell death.
Owing to lagging or insufficient neo-angiogenesis, hypoxia is a feature of most solid tumors. Hypoxic tumor regions contribute to resistance against antiproliferative chemotherapeutics, radiotherapy and immunotherapy. Targeting cells in hypoxic tumor areas is therefore an important strategy for cancer treatment. Most approaches for targeting hypoxic cells focus on the inhibition of hypoxia adaption pathways but only a limited number of compounds with the potential to specifically target hypoxic tumor regions have been identified. By using tumor spheroids in hypoxic conditions as screening system, we identified a set of compounds, including the phenothiazine antipsychotic Fluphenazine, as hits with novel mode of action. Fluphenazine functionally inhibits acid sphingomyelinase and causes cellular sphingomyelin accumulation, which induces cancer cell death specifically in hypoxic tumor spheroids. Moreover, we found that functional inhibition of acid sphingomyelinase leads to overactivation of hypoxia stress-response pathways and that hypoxia-specific cell death is mediated by the stress-responsive transcription factor ATF4. Taken together, the here presented data suggest a novel, yet unexplored mechanism in which induction of sphingolipid stress leads to the overactivation of hypoxia stress-response pathways and thereby promotes their pro-apoptotic tumor-suppressor functions to specifically kill cells in hypoxic tumor areas.


Enhanced biohydrogen production from sugarcane bagasse by Clostridium thermocellum supplemented with CaCO3.
Clostridium thermocellum ATCC 27405 was used to degrade sugarcane bagasse (SCB) directly for hydrogen production, which was significantly enhanced by supplementing medium with CaCO3. The effect of CaCO3 concentration on the hydrogen production was investigated. The hydrogen production was significantly enhanced with the CaCO3 concentration increased from 10mM to 20mM. However, with the CaCO3 concentration further increased from 20mM to 100mM, the hydrogen production didn't increase further. Under the optimal CaCO3 concentration of 20mM, the hydrogen production reached 97.83±5.19mmol/L from 2% sodium hydroxide-pretreated SCB, a 116.72% increase over the control (45.14±1.03mmol/L), and the yield of hydrogen production reached 4.89mmol H2/g SCBadded. Additionally, CaCO3 promoted the biodegradation of SCB and the growth of C. thermocellum. The stimulatory effects of CaCO3 on biohydrogen production are mainly attributed to the buffering capacity of carbonate. The study provides a novel strategy to enhance biohydrogen production from lignocellulose.


Outstations of the Golgi complex are present in the processes of cultured rat oligodendrocytes.
Primary cultures of rat oligodendrocytes were incubated with a fluorescent sphingolipid precursor, 6-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]hexanoylceramide+ ++ (C6-NBD-ceramide). This compound is known to stain the Golgi complex specifically. Within 30 min of incubation at 37 degrees C most of the C6-NBD-ceramide was incorporated into the perinuclear Golgi system, as revealed by conventional and confocal laser fluorescence microscopy. Interestingly, C6-NBD-ceramide was found to accumulate also in smaller, oval-shaped structures in many of the processes, at distances up to 30 microns from the nucleus. This implies the possibility that these structures are Golgi (-derived) complexes. Indeed, after incubation of oligodendrocytes with C6-NBD-ceramide and rhodamine-labeled transferrin both fluorescent labels colocalized in the Golgi system of the cell body as well as in the structures in the processes. Additional support for the Golgi character of these structures was obtained by transmission electron microscopy. Particularly in oligodendrocytes cocultured with neurons, many Golgi structures were present all over the processes. The results lead us to conclude that, in the oligodendrocyte, the Golgi complex does not only reside in the perikaryon, but also in the processes. One can speculate that a polarized biosynthetic activity, involving the presence of the Golgi near the site of myelin synthesis, may be advantageous to the oligodendrocyte for assembly and/or repair of the myelin membrane at the distal end of the processes.


Olfactory cues increase avoidance behavior and induce Fos expression in the amygdala, hippocampus and prefrontal cortex of socially defeated mice.
Genes and proteins of the Fos family are used as markers of neuronal activity and can be modulated by stress. This study investigated whether social defeat (SD) or exposure to an olfactory cue associated with the SD experience activated Fos and FosB/DeltaFosB (ΔFosB) expression in brain regions implicated in the development of post-traumatic stress disorder. Mice exposed to acute SD showed more Fos positive cells in the basolateral amygdala (BLA), CA1 of the hippocampus and the medial prefrontal cortex (mPFC) 1h after SD, and had greater expression of the more persistent FosB/ΔFosB protein in the BLA 24 h after SD compared to controls. Mice exposed to an olfactory cue 24 h or 7 days after SD had higher levels of Fos expression in all three regions 1h after exposure to the cue, and displayed increased avoidance behavior compared to controls. While the avoidance response dissipated with time (less at 7 day vs 24 h after social defeat), Fos expression in the mPFC and CA1 in response to an olfactory cue was greater at 7 days relative to 24 h after social defeat. The results suggest additional processing of the cue-stress association and may provide further support for a role of the mPFC in fear inhibition. These findings may have implications for brain regions and circuitry involved in the avoidance of cues associated with a stressful event that may lead to context-dependent adaptive or maladaptive behavior.