The significance of protein in food intake and body weight regulation.
To highlight the underexposed but important role of protein in food intake and body weight regulation. Protein plays a key role in food intake regulation through satiety related to diet-induced thermogenesis. Protein also plays a key role in body weight regulation through its effect on thermogenesis and body composition. A high percentage of energy from dietary protein limits body weight (re)gain through its satiety and energy inefficiency related to the change in body composition. Protein is more satiating than carbohydrate and fat in the short term, over 24 h and in the long term. Thermogenesis plays a role in this satiety effect, but the role of satiety hormones still needs to be elucidated. On the short-term 'fast' proteins are more satiating than 'slow' proteins, and animal protein induces a higher thermogenesis than vegetable protein. In the longer term the higher postabsorptive satiety and thermogenesis are sustained irrespective of the protein source. High-protein diets affect body weight loss positively only under ad-libitum energy intake conditions, implying also a decreased energy intake. Body composition and metabolic profile are improved. Additional protein consumption results in a significantly lower body weight regain after weight loss, due to body composition, satiety, thermogenesis, and energy inefficiency, while the metabolic profile improves. Implications from these findings are: for practice, recommendations for increasing the percentage of energy from protein while reducing energy intake; for clinical research, assessment of the paradox of increasing the percentage energy from a highly satiating macronutrient; of the potential roles of protein in a negative and positive energy balance; assessment of possibilities of replacing dietary protein by effective amino acids or peptides that may show a similar impact on body weight regulation.


Extracranial association of arteriovenous and venous malformations. Case report.
Association of multiple vascular malformations of the face is a rare condition. An arteriovenous malformation (AVM) with a venous malformation as the draining vein is also a rarity. We report a case of extracranial mixed vascular malformations that deformed the normal architecture of the lower face. Removal of the AVM was followed by stability of the jaw and tongue malformation, indicating the AVM used the venous malformation as its draining vein. This approach spared the patient severe cosmetic and functional sequelae.


Synthesis and evaluation of [64Cu]PSMA-617 targeted for prostate-specific membrane antigen in prostate cancer.
We radiolabeled a ligand, PSMA-617, of prostate-specific membrane antigen (PSMA) with copper-64 (64Cu), to evaluate the metabolism, biodistribution, and potential of [64Cu]PSMA-617 for PET imaging of prostate cancer. [64Cu]PSMA-617 was synthesized by heating PSMA-617 with [64Cu]CuCl2 in buffer solution at 90°C for 5 min. In vitro uptake was determined in two cell lines of prostate cancer. In vivo regional distributions were determined in normal and tumor-bearing mice. High radiolabeling efficiency of 64Cu for PSMA-617 yielded [64Cu]PSMA-617 with >99% radiochemical purity. In vitro cellular uptake experiments demonstrated the specificity of [64Cu]PSMA-617 for PSMA-positive LNCaP cells. Biodistribution observations of normal mice revealed high uptake of radioactivity in the kidney and liver. PET with [64Cu]PSMA-617 visualized tumor areas implanted by PSMA-positive LNCaP cells in the mice. Two hours after the injection of [64Cu]PSMA-617 into mice, a radiolabeled metabolite was observed in the blood, liver, urine, and LNCaP tumor tissues. [64Cu]PSMA-617 was easily synthesized, and exhibited a favorable biodistribution in PSMA-positive tumors. Although this radioligand shows slow clearance for kidney and high liver uptake, change of its chelator moiety and easy radiolabeling may enable development of new 64Cu or 67Cu-labeled PSMA ligands for imaging and radiotherapy.


Partial purification of a progesterone-inducible messenger RNA (avidin) from hen oviduct.
The messenger RNA (mRNA) for avidin, which represents less than 0.05% of the total cellular proteins, was partially purified from hen oviduct, and the presence of avidin mRNA was shown to depend upon prior stimulation by progesterone. A total nucleic acid extract was subjected to oligo (dT)-cellulose chromatography, followed by Sepharose 4B chromatography, preparative agarose gel electrophoresis, and sucrose gradient centrifugation. The relative purity of each preparation was assessed by translation in a wheat-germ system; avidin messenger RNA activity was measured by specific immunoprecipitation of synthesized proteins. Avidin mRNA was separated from the bulk of the total messenger RNA activity of the oviduct and from all ribosomal RNAs to produce greater than a 1000-fold enrichment of avidin mRNA activity compared with total cellular RNA. Based on the translation assay, the most highly purified fraction contained about 2.5% avidin messenger RNA. Avidin mRNA activity was absent in partially purified mRNA obtained from estrogen-stimulated chick oviducts, but was detected in oviducts following progesterone administration.


Silencing of poly(ADP-ribose) polymerase in plants alters abiotic stress signal transduction.
Transgenic plants with reduced poly(ADP-ribose) polymerase (PARP) levels have broad-spectrum stress-resistant phenotypes. Both Arabidopsis thaliana and oilseed rape (Brassica napus) lines overexpressing RNA interference-PARP constructs were more resistant to various abiotic stress treatments in laboratory and greenhouse experiments without negative effects on growth, development, and seed production. This outperforming stress tolerance was initially attributed solely to a maintained energy homeostasis due to reduced NAD(+) consumption. We show that in PARP2-deficient Arabidopsis plants, the observed abiotic stress resistance can also be explained by alterations in abscisic acid levels that facilitate the induction of a wide set of defense-related genes.


Loss of diaphragm glutathione is associated with respiratory failure induced by resistive breathing.
It has been suggested that oxidant stress may contribute to dysfunction of respiratory muscles undergoing severe work loads. We examined changes in glutathione content and redox status in the diaphragm and intercostal muscles of anesthetized Sprague-Dawley rats exposed to prolonged inspiratory resistive loading while breathing 70% O2. These results were compared with those from control groups breathing air or 70% O2. Changes in liver glutathione were also examined. Freeze-clamping and an enzymatic recycling assay were used. Results show that 1) in controls, glutathione content was higher in the diaphragm than in the intercostals, 2) severe hypercapnic acidosis without hypoxemia was present with loading, 3) total diaphragm glutathione decreased approximately 35% with no increase in glutathione oxidation with resistive breathing, whereas intercostal and liver glutathione remained unchanged, and 4) the drop in diaphragm glutathione correlated significantly with the drop in minute ventilation and the increase in arterial PCO2, whereas it was not directly related to intensity of respiratory muscle activity. In conclusion, although diaphragm susceptibility to oxidant stress may be increased with resistive breathing, it is unlikely that the modest decrease in total glutathione contributed significantly to respiratory failure in this model.


Socioeconomic and particulate air pollution correlates of heart disease risk.
How does risk of heart disease depend on age, sex, smoking, income, education, marital status, and outdoor concentrations of fine particulate matter (PM2.5)? We join data available from the Centers for Disease Control and Prevention (CDC) Behavioral Risk Factor Surveillance (BRFSS) System for years 2008-2012 to US Environmental Protection Agency (EPA) data on county-specific concentrations of fine particulate matter (PM2.5) to quantify associations among these variables and to explore possible causal interpretations. Low income is identified as a direct cause of increased heart disease risk in this data set. The effect depends on age and sex: it is most pronounced for men under age 70 and for women under age 80. Income is significantly associated with all of the other variables examined and confounds the association between PM2.5 and heart disease risk. This association is significant in regression models that exclude income, but not in regression models that include it, both in the data set as a whole and in the subset of observations with PM2.5 < 15 μg/m3. Causal directed acyclic graph (DAG) models and non-parametric model ensemble partial dependence plots confirm that higher incomes reduce heart disease risk, consistent with previous observations of socioeconomic gradients in health risks. They support interpretation of this as a robust causal relation apparent in non-parametric analyses, and hence independent of any specific parametric modeling assumptions.


Chlorophyll breakdown in oilseed rape.
Chlorophyll catabolism accompanying leaf senescence is one of the most spectacular natural phenomena. Despite this fact, the metabolism of chlorophyll has been largely neglegted until recently. Oilseed rape has been used extensively as a model plant for the recent elucidating of structures of chlorophyll catabolites and for investigation of the enzymic reactions of the chlorophyll breakdown pathway. The key reaction which causes loss of green color is catalyzed in a two-step reaction by pheophorbide a oxygenase and red chlorophyll catabolite reductase. In this Minireview, we summarize the actual knowledge about catabolites and enzymes of chlorophyll catabolism in oilseed rape and discuss the significance of this pathway in respect to chlorophyll degradation during Brassica napus seed development.


Factors governing susceptibility to chemical allergy.
Chemical allergy describes adverse health effects that result from the stimulation of specific immune responses by chemicals. Hypersensitivity reactions are the result of normally beneficial immune responses acting inappropriately against benign antigens, causing inflammatory reactions and tissue damage. The two most frequent manifestations of chemical-induced allergy are contact hypersensitivity and respiratory sensitization, both of which can have serious impact on quality of life, and represent a common occupational health problems. Chemical agents cause approximately 30% of cases of occupational asthma and roughly 90% of these cases involve immunological mechanisms (allergy). Over the past few decades industrialized countries have witnessed a significant increase (although the rate of increase has recently slowed) in the prevalence of atopic diseases including atopic rhinitis, bronchial asthma and urticaria. Many factors, both intrinsic and extrinsic, can contribute to the development of chemical allergy. In particular, the immune response can be affected by the genetic background, pathological conditions, hormonal and central nervous system status, etc. and by chemical related factors, e.g. dose level, frequency, route and duration of exposure, biotransformation, pharmacokinetics, chemical reactivity, etc. Furthermore, chemical pollution, indoor environment, diet, vaccination programs and the "hygiene hypothesis" have also been implicated in the increased prevalence of asthma and atopic diseases. Following the influence of condition of exposure, heritable and acquired factors, such as age, genetic background, gender etc. on chemical allergy is discussed.


TbRGG2, an essential RNA editing accessory factor in two Trypanosoma brucei life cycle stages.
In the mitochondria of kinetoplastid protozoa, including Trypanosoma brucei, RNA editing inserts and/or deletes uridines from pre-mRNAs to produce mature, translatable mRNAs. RNA editing is carried out by several related multiprotein complexes known as editosomes, which contain all of the enzymatic components required for catalysis of editing. In addition, noneditosome accessory factors necessary for editing of specific RNAs have also been described. Here, we report the in vitro and in vivo characterization of the mitochondrial TbRGG2 protein (originally termed TbRGGm) and demonstrate that it acts as an editing accessory factor. TbRGG2 is an RNA-binding protein with a preference for poly(U). TbRGG2 protein levels are up-regulated 10-fold in procyclic form T. brucei compared with bloodstream forms. Nevertheless, the protein is essential for growth in both life cycle stages. TbRGG2 associates with RNase-sensitive and RNase-insensitive mitochondrial complexes, and a small fraction of the protein co-immunoprecipitates with editosomes. RNA interference-mediated depletion of TbRGG2 in both procyclic and bloodstream form T. brucei leads to a dramatic decrease in pan-edited RNAs and in some cases a corresponding increase in the pre-edited RNA. TbRGG2 down-regulation also results in moderate stabilization of never-edited and minimally edited RNAs. Thus, our data are consistent with a model in which TbRGG2 is multifunctional, strongly facilitating the editing of pan-edited RNAs and modestly destabilizing minimally edited and never-edited RNAs. This is the first example of an RNA editing accessory factor that functions in the mammalian infective T. brucei life cycle stage.


Drug free universities--trends in illicit drugs use among Kraków university students.
Social survey by questioning people is a significant source of information, valuable for planning and developing of prophylactic strategies. An illicit drugs use among a first-year students of Kraków's universities and factors determining the usage were analysed. The research by completing the questionnaire designed by National Bureau for Drug Prevention, Poland was performed in 725 a first-year students of six Kraków's universities. The students were asked to complete the questionnaire confidentially, while the lecture on psychoactive substances. 83.6% of those polled know some students who use a drugs, 38.3% already initiated into drugs, 61.9% reported that they needed at least one day to get drugs. The male students reach for drugs more often then females, and those first-year students being already 20 years old compared to the younger. The greater risk was also noted among students who rent apartments or when a parents earned together more than 3500 PLN. The medical students reached for drugs more rarely than the others. Our survey is one of the first source of information about trends in the drugs usage by Kraków's students. The results will help to develop a preventive standards and creation of effective anti-drugs campaign to be accomplished by college authorities and the Kraków Environmental Diseases Out-patient Clinic for students and academic teachers. The clinic was organised in 2004.


Acute phase proteins in endemic chronic liver diseases.
Forty patients with chronic liver disease and ten normal controls were investigated for acute phase proteins. Mixed schistosomal cases with chronic hepatitis or cirrhosis showed more marked changes, while pure schistosomal group showed serum levels closer to normal values. This could be a differentiating point between the two categories. Also the more significant changes in the mixed groups indicate more involvement of the immune system in the pathogenesis of those groups.


Relationship between Vitamin D Level and Lipid Profile in Non-Obese Children.
Vitamin D deficiency is associated with not only cardiovascular disease itself but also cardiovascular risk factors, including obesity, hypertension, diabetes, hyperglycemia, and dyslipidemia. This study aimed to investigate the relationship between vitamin D level and lipid profile in non-obese children. A total of 243 non-obese healthy volunteers, aged 9-18 years, were enrolled from March to May 2017. Their height and weight were measured, and body mass index was calculated. Subjects underwent blood tests, including measurements of vitamin D (25(OH)D) level and lipid panels, and were divided into either the vitamin D-deficient group (<20 ng/mL) or normal group. The student's t-test and a simple linear regression analysis were used to estimate the association between vitamin D level and lipid profile. Overall, 69.5% of non-obese children (n = 169) had a 25(OH)D level of less than 20 ng/mL. The vitamin D-deficient group showed higher triglyceride (TG) level and TG/high-density lipoprotein cholesterol (HDL-C) ratio than the normal group (TG level: 90.27 vs. 74.74 mmol/L, p = 0.003; TG/HDL-C ratio: 1.753 vs. 1.358, p = 0.003). Vitamin D level seems to affect the lipid profile, even in non-obese children, and a low vitamin D level may progress to dyslipidemia or obesity in non-obese children.


Identification of Repurpose Drugs by Computational Analysis of Disease-Gene-Drug Associations.
Repurposing of marketed drugs to find new indications has become an alternative to circumvent the risk of traditional drug development by its productivity quality. Despite many approaches, computational analysis has great potential to fuel the development of all-rounder drugs to find new classes of medicine for neglected and rare disease. The genes that can explain variations in drug response associated to disease are more important and significant in drug therapeutics necessitate elucidating the relationships of a gene, drug, and disease. The proposed computational analysis facilitates the discovery of knowledge on both target and disease-based relationships from large sources of biomedical literature spread over different platforms. It uses the utility of text mining for automatic extraction of valuable aggregated biomedical entities (disease, gene, and drug) from PubMed to serves as an input to the analysis of association prediction. The top-ranked associations considered for identification of repurposing drugs and also the hidden associations identified using concurrence principle to extrapolate the new relationships. Such findings are reported as novel and contribute to the knowledge base for pharmacogenomics, would immensely support the discovery and progress of novel therapeutic pathways and patient segment biomarkers.


Chronic obstructive pulmonary disease associated with biomass fuel use in women: a systematic review and meta-analysis.
Chronic obstructive pulmonary disease (COPD) is a major and growing cause of morbidity and mortality worldwide. The global prevalence of COPD is growing faster in women than in men. Women are often exposed to indoor pollutants produced by biomass fuels burning during household activities. We conducted a meta-analysis to establish the association between COPD and exposure to biomass smoke in women.Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we searched MEDLINE and Scopus databases in 31December 2016, with the terms: "wood", "charcoal", "biomass", "solid fuels", "organic fuel", "biofuel", "female", "women", "COPD", "chronic bronchitis", "emphysema", "chronic obstructive pulmonary disease". Studies were eligible if they were case-control or cross-sectional studies involving exposure to indoor biomass smoke, conducted at any time and in any geographic location. Fixed-effects or random-effects meta-analysis was used to generate pooled OR. 24 studies were included: 5 case-control studies and 19 cross-sectional studies. Biomass-exposed individuals were 1.38 times more likely to be diagnosed with COPD than non-exposed (OR 1.38, 95% CI 1.28 to 1.57).Spirometry-diagnosed COPD studies failed to show a significant association (OR 1.20, 95% CI 0.99 to 1.40). Nevertheless, the summary estimate of OR for chronic bronchitis (CB) was significant (OR 2.11, 95% CI 1.70 to 2.52). The pooled OR for cross-sectional studies and case-control studies were respectively 1.82 (95% CI 1.54 to 2.10) and 1.05 (95% CI 0.81 to 1.30). Significant association was found between COPD and biomass smoke exposure for women living as well in rural as in urban areas. This study showed that biomass smoke exposure is associated with COPD in rural and urban women.In many developing countries, modern fuels are more and more used alongside traditional ones, mainly in urban area. Data are needed to further explore the benefit of the use of mixed fuels for cooking on respiratory health, particularly on COPD reduction.


On a charitable mission.
Volunteer physicians answered the call over the summer to care for Central American immigrants crossing the border from Mexico into Texas. Nearly 100,000 unaccompanied minors and families flooded into the United States from October 2013 to August 2014.


A Perspective on Nrf2 Signaling Pathway for Neuroinflammation: A Potential Therapeutic Target in Alzheimer's and Parkinson's Diseases.
Neuroinflammation plays a pivotal role in Alzheimer's disease (AD) and Parkinson's disease (PD), the leading causes of dementia. These neurological disorders are characterized by the accumulation of misfolded proteins such as amyloid-ß (Aß), tau protein and α-synuclein, contributing to mitochondrial fragmentation, oxidative stress, and neuroinflammation. Misfolded proteins activate microglia, which induces neuroinflammation, expression of pro-inflammatory cytokines and subsequently facilitates synaptic damage and neuronal loss. So far, all the proposed drugs were based on the inhibition of protein aggregation and were failed in clinical trials. Therefore, the treatment options of dementia are still a challenging issue. Thus, it is worthwhile to study alternative therapeutic strategies. In this context, there is increasing data on the pivotal role of transcription factor NF- E2 p45-related factor 2 (Nrf2) on the redox homeostasis and anti-inflammatory functions in neurodegenerative disorders. Interestingly, Nrf2 signaling pathway has shown upregulation of antioxidant genes, inhibition of microglia-mediated inflammation, and improved mitochondrial function in neurodegenerative diseases, suggesting Nrf2 activation could be a novel therapeutic approach to target pathogenesis. The present review will examine the correlation between Nrf2 signaling with neuroinflammation in AD and PD.


DM27, an enaminone, modifies the in vitro transport of antiviral therapeutic agents.
For most antiviral drugs, low or variable bioavailability is attributed to poor absorption, susceptibility to efflux, or first pass metabolism. Enaminones are beta dicarbonyl compounds, which display P-glycoprotein (P-gp) substrate properties with high efflux ratios. This study investigates the influence of DM27, an enaminone, on the in vitro transport of antiviral agents and the possibility of using DM27 as a P-gp inhibitor to prevent the efflux of certain antiretroviral agents. The transport of [3H]amprenavir, [3H]saquinavir, [3H]ritonavir, [14C]zidovudine (AZT) and [3H]acyclovir was evaluated across Caco-2 cells with DM27 (10(-10)-10(-4) M). In addition, the effect of DM27 (10(-6) M) on the transport of transcellular and paracellular markers was tested to evaluate its influence on these transport pathways. The apparent permeability coefficient (Papp) for each drug or marker was calculated with/without DM27 and toxicity evaluation for DM27 was performed using the MTS assay. The mean Papp for the investigated antiviral agents significantly increased by 22%-51% after DM27 incubation without any toxicity to the Caco-2 cells. In addition, DM27 did not influence the transcellular or paracellular transport of propranolol and mannitol, respectively. DM27, an enaminone, increased the transport of antiretroviral drugs and acyclovir in a nontoxic manner without affecting the paracellular or transcellular transport of these drugs. This study suggests that DM27 may be used as a P-gp efflux inhibitor to enhance the oral bioavailability of antiviral drugs and that drug-drug interactions will most probably be encountered upon co-administration of P-gp substrate drugs with enaminones.


Isolated straight sinus thrombosis: clinical and neuroradiologic correlates.
A rare case of straight sinus thrombosis in a 36-year-old female with sudden onset of status migrainosus is presented. This condition was demonstrated by a linear density in the midline on a noncontrast computed tomography scan, as a filling defect at the location of straight sinus on magnetic resonance imaging, and by the inability to visualize blood flow in the straight sinus on magnetic resonance venography, with a similar demonstration on a 4-vessel digital subtraction angiography.


Fetal toxicity of benzodiazepines in rats.
This study was undertaken to evaluate fetal toxicity of benzodiazepine derivatives, nitrazepam, oxazepam, nimetazepam, clonazepam, diazepam and chlordiazepoxide. In fetotoxicities induced by the oral administration of these six drugs (100 mg/kg), nitrazepam (NTZ) and nimetazepam caused a great damage to the fetus compared with other analogues. The fetotoxicity of NTZ was dose-dependent at a dose of 50 to 100 mg/kg p.o. and its peak toxicity was observed in the group treated from the 8th to 10th day of gestation. Maternal serum and whole fetus concentration of NTZ were higher than that of diazepam which showed weak toxicity. It was suggested that the intensity of fetotoxicity induced by benzodiazepines was related to the amount of drug in blood of dam.


3D-OSEM and FP-CIT SPECT quantification: benefit for studies with a high radius of rotation?
Dopamine transporter imaging with single-photon emission computed tomography (SPECT) is a valuable tool for both clinical routine and research studies. Recently, it was found that the image quality could be improved by introduction of the three-dimensional ordered subset expectation maximization (3D-OSEM) reconstruction algorithm, which provides resolution recovery. The aim of this study was to systematically evaluate the potential benefits of 3D-OSEM in comparison with 2D-OSEM under critical imaging conditions, for example, scans with a high radius of rotation. Monte Carlo simulation scans of a digital brain phantom with various disease states and different radii of rotation ranging from 13 to 30 cm were reconstructed with both 2D-OSEM and 3D-OSEM algorithms. Specific striatal binding and putamen-to-caudate ratios were determined and compared with true values in the phantom. The percentage recovery of true striatal binding was similar between both reconstruction algorithms at the minimum rotational radius; however, at the maximum rotational radius, it decreased from 53 to 43% for 3D-OSEM and from 52 to 26% for 2D-OSEM. 3D-OSEM matched the true putamen-to-caudate ratios more closely than did 2D-OSEM in scans with high SPECT rotation radii. 3D-OSEM offers a promising image quality gain. It outperforms 2D-OSEM, particularly in studies with limited resolutions (such as scans acquired with a high radius of rotation) but does not improve the accuracy of the putamen-to-caudate ratios. Whether the benefits of better recovery in studies with higher radii of rotation could potentially increase the diagnostic power of dopamine transporter SPECT in patients with borderline striatal radiotracer binding, however, needs to be further examined.


Infection due to acyclovir resistant herpes simplex virus in patients undergoing allogeneic hematopoietic stem cell transplantation.
Over an eight-month period from October 1997 to May 1998, four patients who had received bone marrow transplant (BMT) from unrelated donor presented with severe mucosal cutaneous infections involving acyclovir resistant herpes simplex virus 1 (HSV-1). The four isolates were acyclovir (ACV) resistant, three of which were also foscarnet resistant as determined by the dye uptake method. The sequencing of the thymidine kinase (TK) gene did not permit to establish a relation between mutations and resistance to ACV. Three patients were considered as clinically cured of their HSV infection by replacement of ACV or foscarnet with either valacyclovir (one case) or cidofovir (two cases) but eventually two of them died of graft vs host disease. One patient died of extensive HSV infection despite administration of cidofovir. This study emphasizes the importance of monitoring the herpes virus resistance to antiviral drugs in bone marrow transplant recipients and the usefulness of the evaluation of novel antiviral drug for treatment of infections due to strains of HSV resistant to ACV and foscarnet that occur in about 5% of immunocompromised patients.


Associations between insulin-like growth factor-I (IGF-I), IGF-binding protein-1, insulin and other metabolic measures after controlling for genetic influences: results from middle-aged and elderly monozygotic twins.
It has previously been shown that the serum levels of insulin-like growth factor-I (IGF-I), IGF-binding protein-1 (IGFBP-1), and insulin are influenced by genetic effects to various degrees. From a clinical and preventive point of view, however, it is important to identify potentially modifiable non-genetic factors influencing the levels of these measures. Because monozygotic twin pairs share the same genetic background, differences in phenotypic levels within monozygotic twin paris are believed to be due to non-genetic influences. Accordingly, the associations between intrapair differences in one phenotype and intrapair differences in another phenotype are also due to non-genetic influences. The present sample of 97 pairs of monozygotic twins from the population-based Swedish Adoption/Twin Study of Aging (SATSA) provided the opportunity to assess non-genetic influences on the levels of IGF-I, IGFBP-1, and insulin. Several metabolic measures were found to account for the variation of IGF-I, IGFBP-1, and insulin after controlling for the genetic influences. IGFBP-1 and glucose were significant predictors for the levels of IGF-I. IGFBP-1 and glucose together explained about one quarter of the non-genetic variation of IGF-I. However, when IGFBP-1 was dropped from the regression model, insulin was the only independent predictor of IGF-I, and explained about 19% of the non-genetic variation for IGF-I. For IGFBP-1, insulin and IGF-I, were the significant non-genetic predictors. Insulin and IGF-I explained about 28 and 8% respectively of the non-genetic variation for IGFBP-1, while for insulin, IGF-I, triglycerides, body height, glucose, and body mass index (BMI) explained approximately 20, 12, 6, 5 and 5% respectively of the non-genetic variation.


Can undoped calcium tetraborides exist? An answer from the comparison of its density functional theory electronic structure with that of rare-earth metal tetraboride.
Periodic density functional theory calculations are used to discuss the existence of metal tetraborides MB4 with divalent metals. Tetraborides which contain metal atoms inserted in a three-dimensional boron network made of B6 octahedra and B2 dumbbells exhibit a pseudo energy gap for a count of 60 valence electrons per M4(B6)2(B2)2 formula unit. Such a count satisfies the stability electron requirement for B6(2-) (20 electrons) octahedra and B2(2-) (8 electrons) units and allows the filling of two supplementary low-lying bands deriving from the valence metallic d atomic orbitals. This favored electron count is not reached for CaB4 which is then formally deficient by one electron per metal atom. This indicates that CaB4 is unlikely to exist without n-doping.


[Diffuse pseudopolyposis of the colon: developmental form or cicatricial of hemorrhagic rectocolitis?].
The authors report the case of a patient with generalized polyposis associated with ulcerative colitis. The diagnosis of polyposis was made 20 years after the onset of colitis. The patient presented with the unusual clinical manifestations, ie poor general condition and severe denutrition, following a severe relapse of colitis. The mucosal surface of the entire colon, except the rectum, was covered by innumerable polyps, without any macroscopic or microscopic evidence of ulceration. Intestinal protein loss, as assessed by alpha-1-antitrypsin clearance, was very high (470 ml/d). Acute mucosal inflammation, as assessed by histologic study and by 111-Indium-labelled-leukocyte scintigraphy, was also present. The patient responded dramatically to total colectomy with ileorectal anastomosis. Histologically, the polyps were filiform, with a central core, containing vessels and smooth muscle fibers. This observation demonstrates that generalized polyposis, generally considered to be an asymptomatic sequela of ulcerative colitis, can also be associated with severe attacks of colitis.


Dietary habits and dietary nutrient intake in patients with age-related macular degeneration: A case-control study.
Age-related macular degeneration (AMD) is the leading cause of irreversible blindness among older adults in developed countries. Although many risk factors are known, the pathogenesis of AMD is still unclear. However, oxidative stress probably plays a vital role in the process of AMD. The increasing prevalence of AMD, risk of vision loss, limited treatment of dry form, expensive treatment of wet form, and decreased quality of life are factors that lead to considering modifiable risk factors of AMD, such as nutrition. This is the first study describing the relationship between dietary habits, dietary nutrient intake and AMD in the Czech Republic. In this research, a total of 93 cases with AMD and 58 controls without AMD and cataracts participated. All participants were ophthalmologically examined at the Clinic of Eye Treatments at the University Hospital Brno. Data were collected using a pre-tested self-report questionnaire in a face-to-face interview. Food consumption frequency was assessed by an 18-item semiquantitative food-frequency questionnaire (FFQ). Dietary nutrient intakes were calculated from a 24-hour recall. Patients with AMD compared with controls had significantly higher consumption of legumes and lower consumption of meat products, salt and salty products. In men, we found statistically significant differences in alcohol consumption. The case group consumed alcoholic beverages more frequently (median: 2 times a week) than the control group (median: 1-3 times a month). No differences in alcohol consumption were found in women. In comparison to the case group, the control group had a significantly higher dietary intake of energy (5,783.8 vs. 4,849.3 kJ/day; p = 0.002), proteins (65.3 vs. 52.3 g/day; p = 0.002), fats (57.6 vs. 49.4 g/day; p = 0.046), saturated fatty acids (21.7 vs. 18.9 g/day; p = 0.026), carbohydrates (150.4 vs. 127.1 g/day; p = 0.017), dietary fibre (13.2 vs. 11.3 g/day; p = 0.044), vitamin B2 (1.0 vs. 0.9 mg/day; p = 0.029), vitamin B3 (13.9 vs. 10.0 mg/day; p = 0.011), pantothenic acid (3.5 vs. 2.8 mg/day; p = 0.001), vitamin B6 (1.3 vs. 1.0 mg/day; p = 0.001), potassium (1,656.5 vs. 1,418.0 mg/day; p = 0.022), phosphorus (845.4 vs. 718.7 mg/day; p = 0.020), magnesium (176.5 vs. 143.0 mg/day; p = 0.012), copper (1.0 vs. 0.8 mg/day; p = 0.011), and zinc (7.1 vs. 6.1 mg/day; p = 0.012) counted from a 24-hour recall. According to FFQ, dietary habits in the patients with AMD and controls were similar. In men from the case group, we found statistically significant higher alcohol consumption. According to a 24-hour recall, the controls achieved recommended dietary intakes rather than cases. In comparison to the case group, the control group had a significantly higher dietary intake of energy, proteins, fats, saturated fatty acids, carbohydrates, dietary fibre, vitamin B2, vitamin B3, pantothenic acid, vitamin B6, potassium, phosphorus, magnesium, copper, and zinc.


trans-Bis[3-(2-fluorophenyl)-1-(4-nitrophenyl)triazenido-kappaN3]bis(pyridine-kappaN)palladium(II).
In the title complex, [Pd(C(12)H(8)FN(4)O(2))(2)(C(5)H(5)N)(2)] or trans-[Pd(FC(6)H(4)N=N-NC(6)H(4)NO(2))(C(5)H(5)N)(2)], the Pd atom lies on a centre of inversion in space group P-1. The coordination geometry about the Pd(2+) ion is square planar, with two deprotonated 3-(2-fluorophenyl)-1-(4-nitrophenyl)triazenide ions, FC(6)H(4)N=N-NC(6)H(4)NO(2)(-), acting as monodentate ligands (two-electron donors), while two neutral pyridine molecules complete the metal coordination sphere. The whole triazenide ligand is not planar, with the largest interplanar angle being 16.8 (5) degrees between the phenyl ring of the 2-fluorophenyl group and the plane defined by the N=N-N moiety. The Pd-N(triazenide) and Pd-N(pyridine) distances are 2.021 (3) and 2.039 (3) A, respectively.


Role of intravascular ultrasound in coronary artery disease: a new gold standard? An overview.
Although selective contrast coronary arteriography has been the gold standard approach for coronary imaging since more than 30 years, new coronary imaging techniques are currently under development. Intravascular ultrasound (IVUS) is perhaps the most promising of these additional techniques. IVUS makes use of miniaturised crystals incorporated at catheter tips and provides real time, cross-sectional and longitudinal, high resolution images of the arterial wall with three-dimensional reconstruction capabilities (Pandian, 1989; Coy et al., 1991; Liebsen & Klein, 1992). Different devices have been constructed. Actually two types are being used: mechanical (hand-rotated or motor-driven) systems and phased array systems using high-frequency (20-30 MHz) transducers (Bom et al., 1989). Coronary ultrasound imaging performed during catheterization is feasible and safe as demonstrated in several studies examining normal and pathologic coronary arteries (De Scheerder et al., in press).


Captive breeding challenges posed by Malaysian and Bornean Peacock-pheasants (Polyplectron malacense and P. schleiermacheri).
We describe unique reproductive features of two threatened Galliformes species, the Malaysian peacock-pheasant (Polyplectron malacense) and Bornean peacock-pheasant (P. schleiermacheri). These features pose challenges to successful captive breeding to build up sustainable populations for conservation purposes. Single egg clutches in both species mean that reproductive rates are low and population increase is slow. The very rounded eggs of Bornean Peacock-pheasant cause difficulties for egg orientation in incubators. Single chicks with special requirements are poorly suited to rearing by broody bantams and successful husbandry requires increased human time, commitment, and skills.


Fermi level position, Coulomb gap, and Dresselhaus splitting in (Ga,Mn)As.
Carrier-induced nature of ferromagnetism in a ferromagnetic semiconductor, (Ga,Mn)As, offers a great opportunity to observe novel spin-related phenomena as well as to demonstrate new functionalities of spintronic devices. Here, we report on low-temperature angle-resolved photoemission studies of the valence band in this model compound. By a direct determination of the distance of the split-off band to the Fermi energy EF we conclude that EF is located within the heavy/light hole band. However, the bands are strongly perturbed by disorder and disorder-induced carrier correlations that lead to the Coulomb gap at EF, which we resolve experimentally in a series of samples, and show that its depth and width enlarge when the Curie temperature decreases. Furthermore, we have detected surprising linear magnetic dichroism in photoemission spectra of the split-off band. By a quantitative theoretical analysis we demonstrate that it arises from the Dresselhaus-type spin-orbit term in zinc-blende crystals. The spectroscopic access to the magnitude of such asymmetric part of spin-orbit coupling is worthwhile, as they account for spin-orbit torque in spintronic devices of ferromagnets without inversion symmetry.


Are so-called cancer-testis genes expressed only in testis?
Cancer-testis (CT) antigens are a group of tumor-associated antigens with restricted expression in normal tissues except for testis and expression in a wide variety of tumor tissues. This pattern of expression makes them suitable targets for immunotherapy as well as potential biomarkers for early detection of cancer. However, some genes attributed to this family are now known to be expressed in other normal tissues which put their potential applications in immunotherapy and cancer detection under question. Here we analyzed expression of two previously known CT antigens, RHOXF2 and PIWIL2, in AML patients versus normal donors and found no significant difference in the expression of these genes between the two groups. As these two genes showed expression in normal leukocytes, their expression pattern seems to be wider than to be attributed to the CT gene family. Future research should focus on the expression profiles of so called CT antigens to find those with more testis specific expression.


New type of vacancy-induced localized States in multilayer graphene.
We demonstrate the existence of a new type of zero energy state associated with vacancies in multilayer graphene that has a finite amplitude over the layer with a vacancy and adjacent layers, and the peculiarity of being quasilocalized in the former and totally delocalized in the adjacent ones. In a bilayer, when a gap is induced in the system by applying a perpendicular electric field, these states become truly localized with a normalizable wave function. A transition from a localized to an extended state can be tuned by the external gate for experimentally accessible values of parameters.


SIRT2 mediates NADH-induced increases in Nrf2, GCL, and glutathione by modulating Akt phosphorylation in PC12 cells.
SIRT2 plays important roles in multiple biological processes. It is unclear whether SIRT2 affects antioxidant capacity by modulating Nrf2, a key transcription factor for multiple antioxidant genes. By studying NADH-treated differentiated PC12 cells, we found that NADH induced a significant increase in the nuclear Nrf2, which was prevented by both SIRT2 siRNA and SIRT2 inhibitor, AGK2. SIRT2 siRNA also blocked the NADH-induced increases in glutamate cysteine ligase (GCL) and glutathione. Moreover, SIRT2 siRNA and AGK2 blocked NADH-induced Akt phosphorylation, and inhibition of Akt phosphorylation prevented NADH-induced increases in the nuclear Nrf2 and glutathione. Collectively, our study shows that SIRT2 regulates nuclear Nrf2 levels by modulating Akt phosphorylation, thus modulating the levels of GCL and total glutathione.


High-level expression of rat PC12 tyrosine hydroxylase cDNA in Escherichia coli: purification and characterization of the cloned enzyme.
A rat cDNA containing the complete coding sequence for rat tyrosine hydroxylase (tyrosine 3-monooxygenase, EC 188.8.131.52) was isolated from a rat PC12 cDNA library and subcloned in a bacterial expression plasmid, and large amounts of functional enzyme were produced in Escherichia coli. The recombinant enzyme was purified approximately 20-fold to a final specific activity of 1.8 mumol/min per mg of protein, with a yield of 30%. As much as 1 mg of pure protein could be obtained from 1 g of wet bacterial cells. The purified hydroxylase was shown to be homogeneous by denaturing polyacrylamide electrophoresis and isoelectric focusing. Amino acid analysis of the N terminus (25 residues) revealed 100% identity with rat PC12 tyrosine hydroxylase, as deduced from its cDNA sequence. Several of the kinetic properties of the recombinant enzyme resembled those of the native PC12 hydroxylase. However, in contrast to the native enzyme, the purified recombinant hydroxylase was shown to be in an activated form. Phosphorylation with cAMP-dependent protein kinase resulted in stoichiometric incorporation of phosphate, but the kinetic profile of the recombinant enzyme was unaffected. Several clues to these differences are considered that may provide insight into the structural features important to the regulation of tyrosine hydroxylase.


Service costs of caring for adolescents with mental illness in a rural community, 1993-2000.
Costs of treating child psychiatric disorders fall on educational, primary care, juvenile justice, and social service agencies as well as on psychiatric services. The authors estimated multiagency mental health costs by integrating service unit costs with utilization rates in an 11-county area. Using psychiatric diagnoses made independently of service use records, the authors calculated costs across agencies as well as the extent of unmet need for psychiatric care. Annual parent and child reports were used to measure mental health care needs and units of service across 21 types of settings for the population-based Great Smoky Mountain Study sample of 1,420 adolescents from ages 13 to 16. Unit costs for services were generated from information from service providers and records. The authors calculated costs overall, costs by type of service, and costs by diagnosis. Average annual costs per adolescent treated were $3,146. Juvenile justice and inpatient/residential facilities accounted for well over half of the total costs. Costs for youths with two or more diagnoses were twice as much as costs of those with a single disorder. Among adolescents with service needs, 66.9% received no services. Public health insurance was associated with higher rates of specialty mental health care than either private insurance or no insurance. Annual costs across all services were three to four times greater than recent health insurance estimates alone. Many costs for adolescents with mental health problems were borne by agencies not designed primarily to provide psychiatric or psychological services. Only one in three adolescents needing psychiatric care received any mental health services.


Expression of simple epithelial cytokeratins in bovine pulmonary microvascular endothelial cells.
Polypeptides of bovine aortic, pulmonary artery, and pulmonary microvascular endothelial cells, as well as vascular smooth muscle cells and retinal pericytes were evaluated by two-dimensional gel electrophoresis. The principal cytoskeletal proteins in all of these cell types were actin, vimentin, tropomyosin, and tubulin. Cultured pulmonary microvascular endothelial cells also expressed 12 unique polypeptides including a 41 kd acidic type I and two isoforms of a 52 kd basic type II simple epithelial cytokeratin microvascular endothelial cell expression of the simple epithelial cytokeratins was maintained in cultured in the presence or absence of retinal-derived growth factor, and regardless of whether cells were cultured on gelatin, fibronectin, collagen I, collagen IV, laminin, basement membrane proteins, or plastic. Cytokeratin expression was maintained through at least 50 population doublings in culture. The expression of cytokeratins was found to be regulated by cell density. Pulmonary microvascular endothelial cells seeded at 2.5 X 10(5) cell/cm2 (confluent seeding) expressed 3.5 times more cytokeratins than cells seeded at 1.25 X 10(4) cells/cm2 (sparse seeding). Vimentin expression was not altered by cell density. By indirect immunofluorescence microscopy it was determined that the cytokeratins were distributed cytoplasmically at subconfluent cell densities but that cytokeratin 19 sometimes localized at regions of cell-cell contact after cells reached confluence. Vimentin had a cytoplasmic distribution regardless of cell density. These results suggest that pulmonary microvascular endothelial cell have a distinctive cytoskeleton that may provide them with functionally unique properties when compared with endothelial cells derived from the macrovasculature. In conjunction with conventional endothelial cell markers, the presence of simple epithelial cytokeratins may be an important biochemical criterion for identifying pulmonary microvascular endothelial cells.


[Adenocarcinomas of the ethmoid sinus: retrospective analysis of prognostic factors].
Determinate the different prognostic factors of survival in ethmoidal sinus adenocarcinomas (ADK). 60 patients with ethmoidal sinus ADK. 59 men and one woman. Average of 62.2 years (41-82). Retrospective study between 1985 and 2005. The following data were analyzed: exposure time to wood dust, disease incidence, primary clinical symptoms and ASA score. Radiological data were recovered by tomodensitometry and magnetic resonance imaging. Histological groups were described. TNM classification according to UICC 2002 and Roux/Brasnu was established on clinical and radiological constatations. Different treatments used were analyzed. Estimate of survival rate and impact of different prognostic factors were based on Kaplan-Meier actuarial method and multivariate analysis. Incidence rate was 2.86 patients a year. Exposure average time to wood dust was 25.6 years (2-44). T3/T4 stages were predominant (66.7%). the survival rate was 46.5% at 5 years. The survival rate was significantly superior respectively in T1 and T2 stages than in T3 and T4 stages, and in T4a than in T4b stages. Extension of the lesion to the sphenoid sinus was revealed as a significant bad prognostic factor. The ASA score and the exposure time to wood dust were not identified as statistically significant prognosis factors. Survival factors of ethmoïd sinus ADK were T stage and the extension of the tumor to the sphenoid sinus. On the results of this study, we consider that extension in sphenoïd sinus could be include in TNM classification of ethmoïd sinus adenocarcinomas.


Chondrosarcoma of Iliac Bone Imaging Spectrum With Histopathological Correlation: A Case Report.
Chondrosarcoma is a rare form of carcinoma that originates in the cells of cartilage, the flexible tissue that cushions the joints and gives structure to various parts of the body. This malignant tumour primarily affects adults and is most commonly found in the bones of the arms, legs, pelvis, and ribs. The severity and prognosis of chondrosarcoma can vary widely depending on factors such as tumour size, location, and grade. We are reporting a case of an 83-year-old male patient who presented with swelling over the left hip joint. A mass was detected on radiograph and ultrasound that was further characterized using contrast-enhanced CT and MRI. Imaging findings suggested chondrosarcoma. The patient was diagnosed on histopathological examination.


Acceptability of Implants for HIV Treatment in Young Children: Perspectives of Health Care Providers in Johannesburg, South Africa.
In South Africa, less than half of children receiving antiretroviral therapy are virally suppressed. Adherence challenges include poor palatability of drugs and high pill burden. Subcutaneous implants offer a long-acting alternative to daily oral dosing regimens, which may improve outcomes in children living with HIV (CLWH). Qualitative in-depth interviews were conducted with 24 health care providers (HCPs) in Johannesburg, South Africa. Interviews were audio-recorded and transcribed. Data were coded and analyzed using NVivo 12 software and a Grounded Theory approach. Most HCPs welcomed an implant option for CLWH. Perceived benefits included fewer clinic visits, improved adherence, and "normalization" of the lives of CLWH. Concerns included painful insertion and removal, the potential for stigmatization, and caregivers' likely rejection of biodegradable implants. A single, small, non-transparent rod with some flexibility was preferred by most participants. HCP training and early outreach to mitigate potential misinformation about implants and caregivers' fears about biodegradable implants were emphasized. Further engagement with caregivers of CLWH is required and ongoing.


First metatarsophalangeal joint replacement with total arthroplasty in the surgical treatment of the hallux rigidus.
The hallux rigidus, especially in advanced stage, has always been a challenge as regards the surgical treatment. Over the years there have been various surgical techniques proposed with the aim of relieving pain, correcting deformity and maintain a certain degree of movement. For some years we have addressed the problem with the replacement metatarsophalangeal joint arthroplasty with Reflexion system. As far as our experience we have operated and monitored 25 patients (18 females and 7 males) of mean age 58.1 years, operated with this technique from June 2008 to June 2011. It reached an average ROM of 72° (extension and flexion 45° and 27°) with a good functional recovery in 8 patients, and this articulation was good (50° - 40°) in 12 patients and moderate in 5 with a articular range from 40°- 30°. The clinical results, according to our experience, appear to be favorable, as even patient satisfaction is complete.


Determination of ebselen-sensitive reactive oxygen metabolites (ebROM) in human serum based upon N,N'-diethyl-1,4-phenylenediamine oxidation.
Oxidative stress occurs through free radical- and non-radical-mediated oxidative mechanisms, but these are poorly discriminated by most assays. A convenient assay for oxidants in human serum is based upon the Fe(2+)-dependent decomposition of peroxides to oxidize N,N'-diethyl-1,4-phenylenediamine (DEPPD) to a stable radical cation which can be measured spectrophotometrically. We investigated modification of the DEPPD oxidation assay to discriminate color formation due to non-radical oxidants, including hydroperoxides and endoperoxides, which are sensitive to ebselen. Use of serum, which has been pretreated with ebselen as a reference, provides a quantitative assay for non-radical, reactive oxidant species in serum, including hydroperoxides, endoperoxides and epoxides. In a set of 35 human serum samples, non-radical oxidants largely accounted for DEPPD oxidation in 86% of the samples while the remaining 14% had considerable contribution from other redox-active chemicals. The simple modification in which ebselen-pretreated sample is used as a reference provides means to quantify non-radical oxidants in human serum. Application of this approach could enhance understanding of the contribution of different types of oxidative stress to disease.


History of the cholesterol controversy in Britain.
The lipid hypothesis, the concept that cholesterol plays a causal role in atherosclerosis and cardiovascular disease, has been the subject of a controversy which started in the 1950s, peaked in the 1970s and 80s and then subsided in the 1990s. It was finally resolved by the positive outcome of the Scandinavian Simvastatin Survival Study, the first of 14 prevention trials using statins which showed that lowering cholesterol reduced both cardiovascular events and total mortality. This commentary focuses primarily on the events and people involved in the cholesterol controversy in Britain. The foremost critics of the lipid hypothesis are now deceased but unfortunately for many of the patients with hypercholesterolaemia and coronary heart disease it took the best part of 50 years to disprove the sceptics. This brief account relates why it took so long.


A quantitative analysis of interactions between photoreceptors in the salamander (Ambystoma) retina.
A quantitative description of the electrical properties of the photoreceptor layer in the salamander retina was obtained from earlier data on the characteristics of isolated rods and cones and on rod-rod coupling, and from new data on rod-cone and cone-cone coupling and on the rod photocurrent. Injecting -1 nA current into a rod elicits hyperpolarizations of about 20 mV in an adjacent rod and 4 mV in an adjacent cone. Responses of more distant receptors are smaller. Injecting -1 nA into a cone elicits hyperpolarizations of about 4 mV in an adjacent rod and 0.4 mV in a nearby cone. Depolarizing current evokes smaller responses. Assuming, in agreement with anatomical evidence, that each rod is electrically coupled to four rods and to four cones around it, and that there is no direct electrical coupling between cones, we found these results could be predicted from the properties of isolated rods and cones if adjacent rods are coupled by a resistance of 300 M omega and adjacent rods and cones are coupled by a resistance of 5000 M omega. The small cone-cone coupling seen is due to coupling via intervening rods. The two halves of double cones are not electrically coupled. The spectral sensitivity of both halves is a maximum around 620 nm wave-length. The rod photocurrent has been characterized by voltage-clamping rods isolated from the retina. In agreement with Bader, MacLeish & Schwartz (1979) we found the time course of the photocurrent to be approximately independent of voltage between -35 and -85 mV. The voltage responses of rods, single cones and double cones isolated from the retina obey the principle of univariance. Responses of receptors in the retina do not obey univariance. The main deviations from univariance observed can be explained if adjacent rods and cones are coupled by a resistance of 5000 M omega. Our data demonstrate that rod-cone coupling is relatively weak. We simplified our description of the photoreceptor network, by omitting cones, to investigate the spatiotemporal processing that the rod network is capable of. Computer simulations predict, as is found experimentally, that the rod voltage response to a large spot of bright light should show a much more pronounced initial transient hyperpolarization than the response to a small spot of light of the same intensity. This difference is produced by the combination of electrical coupling of the rods with the existence of a voltage-gated current, IA, in the rod membrane.(ABSTRACT TRUNCATED AT 400 WORDS)


Metabolic regulation of growth hormone by free fatty acids, somatostatin, and ghrelin in HIV-lipodystrophy.
Human immunodeficiency virus (HIV)-lipodystrophy is a syndrome characterized by changes in fat distribution and insulin resistance. Prior studies suggest markedly reduced growth hormone (GH) levels in association with excess visceral adiposity among patients with HIV-lipodystrophy. We investigated mechanisms of altered GH secretion in a population of 13 male HIV-infected patients with evidence of fat redistribution, compared with 10 HIV-nonlipodystrophic patients and 11 male healthy controls similar in age and body mass index (BMI). Although similar in BMI, the lipodystrophic group was characterized by increased visceral adiposity, free fatty acids (FFA), and insulin and reduced extremity fat. We investigated ghrelin and the effects of acute lowering of FFA by acipimox on GH responses to growth hormone-releasing hormone (GHRH). We also investigated somatostatin tone, comparing GH response to combined GHRH and arginine vs. GHRH alone with a subtraction algorithm. Our data demonstrate an equivalent number of GH pulses (4.1 +/- 0.6, 4.7 +/- 0.8, and 4.5 +/- 0.3 pulses/12 h in the HIV-lipodystrophic, HIV-nonlipodystrophic, and healthy control groups, respectively, P > 0.05) but markedly reduced GH secretion pulse area (1.14 +/- 0.27 vs. 4.67 +/- 1.24 ng.ml(-1).min, P < 0.05, HIV-lipodystrophic vs. HIV-nonlipodystrophic; 1.14 +/- 0.27 vs. 3.18 +/- 0.92 ng.ml(-1).min, P < 0.05 HIV-lipodystrophic vs. control), GH pulse area, and GH pulse width in the HIV-lipodystrophy patients compared with the control groups. Reduced ghrelin (418 +/- 46 vs. 514 +/- 37 pg/ml, P < 0.05, HIV-lipodystrophic vs. HIV-nonlipodystrophic; 418 +/- 46 vs. 546 +/- 45 pg/ml, P < 0.05, HIV-lipodystrophic vs. control), impaired GH response to GHRH by excess FFA, and increased somatostatin tone contribute to reduced GH secretion in patients with HIV-lipodystrophy. These data provide novel insight into the metabolic regulation of GH secretion in subjects with HIV-lipodystrophy.


Single-dose injectable nanovaccine-in-hydrogel for robust immunotherapy of large tumors with abscopal effect.
Current cancer immunotherapy [e.g., immune checkpoint blockade (ICB)] only benefits small subsets of patients, largely due to immunosuppressive tumor microenvironment (TME). In situ tumor vaccination can reduce TME immunosuppression and thereby improve cancer immunotherapy. Here, we present single-dose injectable (nanovaccines + ICBs)-in-hydrogel (NvIH) for robust immunotherapy of large tumors with abscopal effect. NvIH is thermo-responsive hydrogel co-encapsulated with ICB antibodies and novel polymeric nanoparticles loaded with three immunostimulatory agonists for Toll-like receptors 7/8/9 (TLR7/8/9) and stimulator of interferon genes (STING). Upon in situ tumor vaccination, NvIH undergoes rapid sol-to-gel transformation, prolongs tumor retention, sustains the release of immunotherapeutics, and reduces acute systemic inflammation. In multiple poorly immunogenic tumor models, single-dose NvIH reduces multitier TME immunosuppression, elicits potent TME and systemic innate and adaptive antitumor immunity with memory, and regresses both local (vaccinated) and distant large tumors with abscopal effect, including distant orthotopic glioblastoma. Overall, NvIH holds great potential for tumor immunotherapy.


Variability of Transrectal Shear Wave Elastography in a Phantom Model.
This study aimed to assess the variability of transrectal shear wave elastography (SWE) using a designed phantom. In a phantom, the SWE values were examined by two radiologists using agarose and emulsion silicone of different sizes (1, 2, and 3 cm) and shapes (round, cubic) at three depths (1, 2, and 3 cm), two region of interest (ROI) and locations (central, peripheral) using two ultrasound machines (A, B from different vendors). Variability was evaluated using the coefficient of variation (CV). The CVs decreased with increasing phantom size. Significant changes in SWE values included; agarose phantom at 3 cm depth (p < 0.001; machine A), 1 cm depth (p = 0.01; machine B), emulsion silicone at 2 cm depth (p = 0.047, p = 0.020; both machines). The CVs increased with increasing depth. Significant changes in SWE values included; 1 cm agarose (p = 0.037, p = 0.021; both machines) and 2 cm agarose phantom (p = 0.047; machine A). Significant differences in SWE values were observed between the shapes for emulsion silicone phantom (p = 0.032; machines A) and between ROI locations on machine B (p ≤ 0.001). The SWE values differed significantly between the two machines (p < 0.05). The intra-/inter-operator agreements were excellent (intraclass correlation coefficient > 0.9). The phantom size, depth, and different machines affected the variability of transrectal SWE.


A novel point mutation of the RET protooncogene involving the second intracellular tyrosine kinase domain in a family with medullary thyroid carcinoma.
Hereditary medullary thyroid carcinoma, a tumor that arises from the parafollicular cells of the thyroid gland, occurs in isolation (as in familial medullary thyroid carcinoma), in association with hyperparathyroidism and pheochromocytoma (as in multiple endocrine neoplasia type 2A), or in association with pheochromocytoma, marfanoid habitus, and mucosal neuromas (as in multiple endocrine neoplasia type 2B). These genetic syndromes are associated with germline-activating mutations of the RET protooncogene, a cell surface tyrosine kinase receptor, which is believed to modulate specific intracellular signaling pathways involved in the regulation of C cell proliferation and apoptosis. RET-activating mutations involve two important functional areas of the receptor: the cysteine-rich extracellular domain and the intracellular tyrosine kinase domain. Multiple endocrine neoplasia type 2A and familial medullary thyroid carcinoma are more commonly associated with mutations in the cysteine-rich extracellular domain, whereas multiple endocrine neoplasia type 2B is exclusively associated with mutations involving the second intracellular tyrosine kinase domain. Here, we describe a novel missense mutation of the RET protooncogene that substitutes arginine for proline at codon 912 of the intracellular tyrosine kinase domain in a family with medullary thyroid carcinoma.


Tellurium-induced neuropathy: a model for reversible reductions in myelin protein gene expression.
Inclusion of 1.1% tellurium in the diet of developing rats causes a highly synchronous primary demyelination of peripheral nerves, which is followed closely by a period of rapid remyelination. The demyelination is related to the inhibition of squalene epoxidase activity, which results in a block in cholesterol synthesis and accumulation of squalene. We now report that the demyelination resulting from this limiting of the supply of an intrinsic component of myelin (cholesterol) leads to repression of the expression of mRNA for myelin-specific proteins. Tellurium exposure resulted in an increase in total RNA (largely rRNA) in sciatic nerve, which could not be accounted for by cellular proliferation; these increased levels of rRNA may be a reactive response of Schwann cells to toxic insult and may relate to the higher levels of protein synthesis required during remyelination. In contrast, steady-state levels of mRNA, determined by Northern blot analysis, for P0 and myelin basic protein were markedly decreased (levels after 5 days of tellurium exposure were only 10-15% of control levels as a fraction of total RNA and 25-35% of control levels when the increased levels of total RNA were taken into account). Message levels increased during the subsequent period of remyelination and reached near-normal levels 30 days after beginning tellurium exposure. Although message levels for the myelin-associated glycoprotein showed a similar temporal pattern, levels did not decrease as greatly and subsequently increased sooner than did levels for P0 and myelin basic protein. The coordinate alterations in message levels for myelin proteins indicate that Schwann cells can down-regulate and then up-regulate the synthesis of myelin in response to alterations in the supply of membrane components.


MnOx In Situ Growth-Induced Luminescence and Oxidase-Like Feature Bimodulation of CePO4:Tb Nanorods: Toward Ascorbic Acid-Related Bioanalysis in a "One-Stone-Two-Birds" Manner.
Nanozyme-based multimode detection is a useful means to improve the accuracy and stability of analytical methods. However, both multifunctional nanozymes and related multimodal sensing strategies are still very scarce. Besides, they require complex processes to fabricate and operate. To fill this gap, here we propose a spontaneous interfacial in situ growth strategy to prepare a new bifunctional material (CePO4:Tb@MnOx) featuring good oxidase-like activity and green photoluminescence for the dual-mode colorimetric/luminescence determination of ascorbic acid (AA)-related biomarkers specifically. CePO4:Tb@MnOx was gained through the controllable redox reaction between KMnO4 and CePO4:Tb nanorods. It was interestingly found that MnOx in situ growth not only significantly enhanced the enzyme-like activity but also could reversibly regulate the luminescence of CePO4:Tb via a dual quenching mechanism. More interestingly, CePO4:Tb@MnOx exhibited a distinctive response toward AA against other reducing species. A double-coordination regulation mechanism was further verified to clarify the catalytic activity and luminescence switching behaviors in CePO4:Tb@MnOx. Based on these findings, a dual-mode colorimetric/luminescence approach was established for AA sensing in a "one-stone-two-birds" manner, providing excellent selectivity, sensitivity, and practicability. Furthermore, the determination of AA-related biomarkers, including acid phosphatase activity and organophosphorus residue, was also validated by the sensing principle. Our work not only deepens the understanding of the coordinated regulation of the luminescence and enzyme-like features in lanthanide-based materials but also offers a novel way to design and develop multifunctional nanozymes for advanced bioanalytical applications.


Presurgical nasoalveolar moulding in unilateral cleft lip and palate.
Presurgical nasoalveolar moulding (PNAM) is a non-surgical method of reshaping the cleft lip, alveolus, palate and the nose to minimize the severity of the cleft deformity, before primary cheiloplastyand palatoplasty. In this context, PNAM proves to be an invaluable asset in the management of unilateral cleft lip and palate. The study was conducted to evaluate the efficacy of PNAM in the management of unilateral cleft lip and palate with the following objectives: (1) To assess and compare the degree of reduction in the size of cleft palate and alveolus (pre-PNAM and post-PNAM). (2) To evaluate and compare the improvement in columellar length and correction of columellar deviation (pre-PNAM and post-PNAM). (3) To assess the changes in the position of the alar base and the alar cartilages. Prospective study. A prospective study consisting of, which included 20 patients with complete unilateral cleft lip and palate was conducted. The age at the start of PNAM treatment of the infants ranged from 2 to 44 days of age reporting to our institute between December 2011 and August 2013. All the patients underwent PNAM therapy before primary cheiloplasty at 6 months of age; clinical parameters were assessed pre- and post-therapy using photographs and dental study models of the maxilla. Student's t-test for paired comparisons. Results of the study showed a promising reduction in the cleft size before the surgery, significant improvement in nasal symmetry, including the columellar length on the cleft side. PNAM is a valuable adjunct to our surgical armamentarium in dealing with the challenges of primary closure of unilateral cleft lip and palate thereby enhancing the overall surgical outcome. The advantages of this method include the simplicity of the procedure and improving the quality of surgical repair, particularly in obtaining tension free muscle closure in unilateral clefts.


Hospital-associated deconditioning and dysfunction.
A paper published in 1991 in the Journal of the American Geriatrics Society describes hospitalisation as a 'devastating' event for an older person. This was conceptualised as stemming from three discrete processes: the illness itself, adverse effects of treatment and the general effects of deconditioning.


A New MRI-Based Model of Heart Function with Coupled Hemodynamics and Application to Normal and Diseased Canine Left Ventricles.
A methodology for the simulation of heart function that combines an MRI-based model of cardiac electromechanics (CE) with a Navier-Stokes-based hemodynamics model is presented. The CE model consists of two coupled components that simulate the electrical and the mechanical functions of the heart. Accurate representations of ventricular geometry and fiber orientations are constructed from the structural magnetic resonance and the diffusion tensor MR images, respectively. The deformation of the ventricle obtained from the electromechanical model serves as input to the hemodynamics model in this one-way coupled approach via imposed kinematic wall velocity boundary conditions and at the same time, governs the blood flow into and out of the ventricular volume. The time-dependent endocardial surfaces are registered using a diffeomorphic mapping algorithm, while the intraventricular blood flow patterns are simulated using a sharp-interface immersed boundary method-based flow solver. The utility of the combined heart-function model is demonstrated by comparing the hemodynamic characteristics of a normal canine heart beating in sinus rhythm against that of the dyssynchronously beating failing heart. We also discuss the potential of coupled CE and hemodynamics models for various clinical applications.


The two phases of regulated exocytosis in permeabilized pancreatic acini are modulated differently by heterotrimeric G-proteins.
In this study we examined the influence on AlF4- and GTP gamma S on amylase secretion from alpha toxin permeabilized pancreatic acini. AlF4- only activates heterotrimeric G-proteins, whereas GTP gamma S activates both small ras-like GTP-binding proteins and heterotrimeric G-proteins (Kahn, R. A., J. Biol. Chem., 266, 15595-15597, 1991). GTP gamma S, but not AlF4-, significantly stimulated Ca2(+)-independent amylase secretion, suggesting that a small GTP-binding protein controls regulated exocytosis distal to the site of action of Ca2+. In contrast, both AlF4- and GTP gamma S modulated Ca(2+)-dependent amylase secretion. AlF4- and GTP gamma S stimulated the initial rapid, ATP-independent, phase of Ca(2+)-dependent secretion but inhibited the second slower sustained, ATP-dependent, phase of release. There were significant differences in the GTP gamma S requirements for the stimulation and inhibition of Ca(2+)-dependent amylase secretion, consistent with GTP gamma S activating separate heterotrimeric G-proteins to modulate each phase of the Ca(2+)-dependent secretory response. Our studies also indicated that neither G-protein is a member of the Gi/o class of heterotrimeric G-proteins.


Excitability changes of the inspiratory "off-switch" mechanism tested by electrical stimulation in nucleus parabrachialis in the cat.
The time course of the excitability of the inspiratory "off-switch" mechanism with and without phasic vagal stretch receptor feedback has been studied in cats under light pentobarbitone anesthesia by electrical stimulation in the rostral pons using brief tetanic stimulation (300 Hz for 0.2 s). The threshold strength required just to elicit inspiratory "off-switch" was high early in inspiration and fell steeply with time. The threshold curves were steeper with than without phasic vagal feedback, and the difference reflects the phasic vagal contribution to the excitability of the inspiratory "off-switch" the absence of phasic vagal vagal feedback the time course of this threshold curve usually corresponded closely to that of the "integrated" phrenic activity at all PCO2 levels and body temperatures tested indicating that the "integrated" phrenic activity can be used as an index of the centrally generated inspiratory activity. In response to a rise in PCO2 both the rate of change of excitability of the inspiratory "off-switch" mechanism and its initial threshold level was increased. Changes in body temperature caused no change in the initial threshold but produced marked changes in the rate of rise of the "off-switch" excitability; Following an "augmented breath" the inspiratory "off-switch" threshold was markedly reduced


Changes in dynamic arterial elastance induced by volume expansion and vasopressor in the operating room: a prospective bicentre study.
Dynamic arterial elastance (Eadyn), defined as the ratio between pulse pressure variations and stroke volume variations, has been proposed to assess functional arterial load. We evaluated the evolution of Eadyn during volume expansion and the effects of neosynephrine infusion in hypotensive and preload-responsive patients. In this prospective bicentre study, we included 56 mechanically ventilated patients in the operating room. Each patient had volume expansion and neosynephrine infusion. Stroke volume and stroke volume variations were obtained using esophageal Doppler, and pulse pressure variations were measured through the arterial line. Pressure response to volume expansion was defined as an increase in mean arterial pressure (MAP) ≥ 10%. Twenty-one patients were pressure responders to volume expansion. Volume expansion induced a decrease in Eadyn (from 0.69 [0.58-0.85] to 0.59 [0.42-0.77]) related to a decrease in pulse pressure variations more pronounced than the decrease in stroke volume variations. Baseline and changes in Eadyn after volume expansion were related to age, history of arterial hypertension, net arterial compliance and effective arterial elastance. Eadyn value before volume expansion > 0.65 predicted a MAP increase ≥ 10% with a sensitivity of 76% (95% CI 53-92%) and a specificity of 60% (95% CI 42-76%). Neosynephrine infusion induced a decrease in Eadyn (from 0.67 [0.48-0.80] to 0.54 [0.37-0.68]) related to a decrease in pulse pressure variations more pronounced than the decrease in stroke volume variations. Baseline and changes in Eadyn after neosynephrine infusion were only related to heart rate. Eadyn is a potential sensitive marker of arterial tone changes following vasopressor infusion.


Suceptibility of mice to audiogenic seizures is increased by handling their dams during gestation.
Fetal mice treated on days 10, 11, and 12 of gestation by injecting the mothers with (i) 50 milligrams of beta-2-thienylalanine, (ii) solvent, or (iii) sham injection had identical frequencies of audiogenic seizures when tested 23 days after birth; these frequencies were significantly higher than those of an unhandled control group. Results of the sham treatment suggest that maternal stress induced by handling, rather than the nature of the substance injected, increased the susceptibility of the offspring to seizures.


Baseline characteristics and risk factors for short-term outcomes in 132 COVID-19 patients with diabetes in Wuhan China: A retrospective study.
To investigate the clinical characteristics, laboratory findings and high- resolution CT (HRCT) features and to explore the risk factors for in-hospital death and complications of coronavirus disease 2019 (COVID-19) patients with diabetes. From Dec 31, 2019, to Apr 5, 2020, a total of 132 laboratory-confirmed COVID-19 patients with diabetes from two hospitals were retrospectively included in our study. Clinical, laboratory and chest CT data were analyzed and compared between the two groups with an admission glucose level of ≤11 mmol/L (group 1) and >11 mmol/L (group 2). Logistic regression analyses were used to identify the risk factors associated with in-hospital death and complications. Of 132 patients, 15 died in hospital and 113 were discharged. Patients in group 2 were more likely to require intensive care unit care (21.4% vs. 9.2%), to develop acute respiratory distress syndrome (ARDS) (23.2% vs. 9.2%) and acute cardiac injury (12.5% vs. 1.3%), and had a higher death rate (19.6% vs. 5.3%) than group 1. In the multivariable analysis, patients with admission glucose of >11 mmol/l had an increased risk of death (OR: 7.629, 95%CI: 1.391-37.984) and in-hospital complications (OR: 3.232, 95%CI: 1.393-7.498). Admission d-dimer of ≥1.5 μg/mL (OR: 6.645, 95%CI: 1.212-36.444) and HRCT score of ≥10 (OR: 7.792, 95%CI: 2.195-28.958) were associated with increased odds of in-hospital death and complications, respectively. In COVID-19 patients with diabetes, poorly-controlled blood glucose (>11 mmol/L) may be associated with poor outcomes. Admission hyperglycemia, elevated d-dimer and high HRCT score are potential risk factors for adverse outcomes and death.


Hidden slow dynamics in water.
It is well known that the structural and dynamical properties of water are of central importance for life on our planet. However, despite this knowledge its structural and dynamical properties are still far from fully understood. In this Letter we show for the first time that water exhibits an anomalously slow relaxation process, which is about 4 orders of magnitude slower than the viscosity-related structural main relaxation. This slow Debye-like process has previously only been observed in monoalcohols and more recently also in polyalcohols, and due to its slowness it is generally believed to be caused by some kind of collective motion of hydrogen-bonded structures. The new finding has important structural and dynamical implications for water.


Test-retest reliability of peak location in the sensorimotor network of resting state fMRI for potential rTMS targets.
Most stroke repetitive transcranial magnetic stimulation (rTMS) studies have used hand motor hotspots as rTMS stimulation targets; in addition, recent studies demonstrated that functional magnetic resonance imaging (fMRI) task activation could be used to determine suitable targets due to its ability to reveal individualized precise and stronger functional connectivity with motor-related brain regions. However, rTMS is unlikely to elicit motor evoked potentials in the affected hemisphere, nor would activity be detected when stroke patients with severe hemiplegia perform an fMRI motor task using the affected limbs. The current study proposed that the peak voxel in the resting-state fMRI (RS-fMRI) motor network determined by independent component analysis (ICA) could be a potential stimulation target. Twenty-one healthy young subjects underwent RS-fMRI at three visits (V1 and V2 on a GE MR750 scanner and V3 on a Siemens Prisma) under eyes-open (EO) and eyes-closed (EC) conditions. Single-subject ICA with different total number of components (20, 30, and 40) were evaluated, and then the locations of peak voxels on the left and right sides of the sensorimotor network (SMN) were identified. While most ICA RS-fMRI studies have been carried out on the group level, that is, Group-ICA, the current study performed individual ICA because only the individual analysis could guide the individual target of rTMS. The intra- (test-retest) and inter-scanner reliabilities of the peak location were calculated. The use of 40 components resulted in the highest test-retest reliability of the peak location in both the left and right SMN compared with that determined when 20 and 30 components were used for both EC and EO conditions. ICA with 40 components might be another way to define a potential target in the SMN for poststroke rTMS treatment.


Unplanned return to the operating room in patients with adolescent idiopathic scoliosis: are we doing better with pedicle screws?
Prospective, longitudinal cohort. To evaluate the incidence, timing, and risk factors for reoperation in patients with adolescent idiopathic scoliosis (AIS) treated with pedicle screws (PSs) compared with hybrid (Hb) constructs. Rates of return to the operating room (OR) after definitive fusion for AIS vary, with a paucity of data on PS constructs. A prospective multicenter database was retrospectively queried to identify consecutive patients with AIS who underwent posterior spinal fusion with either PS or Hb constructs with a minimum 2-year follow-up. All reoperations were stratified into an early group (<60 d) or a late group (>60 d). Univariate and multivariate logistical analyses were performed to identify potential risk factors related to reoperation. A total of 627 patients met the inclusion criteria (PS = 540, Hb = 87). There was a statistically significant difference in the rate of reoperations between the PS (3.5%) and Hb groups (12.6%), P < 0.001. Early return to the OR occurred in 2.0% of the patients with PS compared with 3.4% in the Hb group, P = 0.43. Late returns to the OR occurred in 1.5% of PS group versus 9.2% of the Hb group, P < 0.001. Multivariate analysis revealed longer operating time as an independent risk factor for an unplanned return to the OR in patients treated with PSs (P < 0.05). Our results suggest that patients with AIS treated with PS have decreased rates of unplanned return to the OR when compared with patients with Hb constructs. The majority of returns to the OR were early (<60 d) for the PS group compared with late (>60 d) for the Hb group. Longer operative times increased the risk of unplanned reoperation for the PS group. 3.


Development of intra-vaginal matrices from polycaprolactone for sustained release of antimicrobial agents.
Microporous poly(ε-caprolactone) matrices were loaded with an antibacterial agent, ciprofloxacin and an antifungal agent, miconazole nitrate, respectively, for investigations of their potential as controlled vaginal delivery devices. Ciprofloxacin loadings up to 15% w/w could be obtained by increasing the drug content of the poly(ε-caprolactone) solution, while the actual loadings of miconazole were much lower (1-3% w/w) due to drug partition into methanol during the solvent extraction. The kinetics of ciprofloxacin release in simulated vaginal fluid at 37 were characterised by a small burst release phase in the first 24 h, low drug release up to 7 days (10%) and gradual release of up to 80% of the drug content by day 30. Meanwhile, the release kinetics of miconazole-loaded matrices could be effectively described by the Higuchi model with 100% drug release from the highest loaded matrices (3.2% w/w) in 13 days. Ciprofloxacin or miconazole released over 30 and 13 days, respectively, from poly(ε-caprolactone) matrices into simulated vaginal fluid retained high levels of antimicrobial activity in excess of 80% of the activity of the free drug. This study confirms the potential of poly(ε-caprolactone) matrices for delivering antimicrobial agents in the form of an intra-vaginal device.


Gadolinium contrast agents- challenges and opportunities of a multidisciplinary approach: Literature review.
Contrast agents is used in magnetic resonance imaging (MRI) to improve the visibility of the details of the organ structures. Gadolinium-based contrast agent (GBCA) has been used since 1988 in MRI for diagnostic and follow-up of patients, the gadolinium good properties make it an effective choice for enhance the signal in MRI by increase its intensity and shortening the relaxation time of the proton. Recently, many studies show a gadolinium deposition in different human organs due to release of free gadolinium various body organs or tissue, which led to increased concern about the use of gadolinium agents, in this study, the potential diseases that may affect the patient and side effects that appear on the patient and related to accumulation of gadolinium were clarified, the study focused on the organs such as brain and bones in which gadolinium deposition was found and the lesions associated with it, and the diseases associated with gadolinium retention includes Nephrogenic Systemic Fibrosis (NSF) and Gadolinium deposition disease (GDD). Some studies tended to improve the contrast agents by developing a new non-gadolinium agents or development of next-generation gadolinium agents. In this review article the latest knowledge about MRI contrast agent.


Body composition changes in male patients with chronic obstructive pulmonary disease: Aging or disease process?
Chronic obstructive pulmonary disease (COPD) mainly affects middle-age and elderly adults. It is unclear if the presence of muscle wasting and fat accumulation in patients with COPD is age or disease-related. This study investigated the effect of age and COPD disease severity on body composition with the aim of identifying a biomarker(s) for COPD. Healthy subjects and patients with COPD of different severity were recruited. Dual-energy X-ray absorptiometry was used to analyze total and segmental body composition. Subjects included in the analysis were classified into four groups: healthy young (aged 20-45 years) (n = 35), healthy old (aged ≥ 60 years) (n = 37), moderate COPD (n = 40), and severe COPD (n = 14). In healthy old adults, leg and limb lean masses were lower by 10.6% and 8.5%, respectively, compared with healthy young adults (P < 0.05). Appendicular lean outcomes were significantly lower in the moderate COPD compared to the healthy old group and were significant lower in subjects with severe COPD compared to those with moderate COPD. All fat depots were similar for both young and old healthy subjects and subjects with moderate COPD, but significantly decreased in patients with severe COPD. This study examined the changes in total and segmental body composition with aging and COPD severity. It found that aging and COPD altered the body composition differently, and the effect was most pronounced in leg lean mass. Remarkably, differences in appendicular lean masses were seen in mild COPD although no changes in body weight or BMI were apparent compared with healthy young adults. In contrast, fat depot changes were only observed in severe COPD. Aging and COPD processes are multifactorial and additional longitudinal studies are required to explore both the quantitative and qualitative changes in body composition with aging and disease process.


Attentional Mechanisms and Improved Residual Networks for Diabetic Retinopathy Severity Classification.
Diabetic retinopathy is a main cause of blindness in diabetic patients; therefore, detection and treatment of diabetic retinopathy at an early stage has an important effect on delaying and avoiding vision loss. In this paper, we propose a feasible solution for diabetic retinopathy classification using ResNet as the backbone network. By modifying the structure of the residual blocks and improving the downsampling level, we can increase the feature information of the hidden layer feature maps. In addition, attention mechanism is utilized to enhance the feature extraction effect. The experimental results show that the proposed model can effectively detect and classify diabetic retinopathy and achieve better results than the original model.


Utilization of mental health services by the aging.
A descriptive study of persons 55 years of age and older who were newly admitted (60 cases) or in ongoing treatment (30 cases) in a mental health center was done as an outgrowth of a utilization review study. The total population of 461 was studied from July 1, 1977, to June 30, 1978. A chart review of 90 cases was performed. The newly admitted subsample was married, was diagnosed as depressed, and had a broad range of dispositions into various treatment modalities. The chronic subsample was single, diagnosed as schizophrenic, and in treatment in a single community-support unit. These differences were statistically significant at the P<.01, P<.001, and P<.001 levels, respectively. Although the newly admitted subsample had no previous contact with psychiatric services, 44 of the 60 patients (73 percent) were on psychoactive medication prescribed by nonpsychiatric physicians. Implications for the training of general medical practitioners and mental health center staff, and the need for ongoing assessment of patients in community support units are discussed, as well as the significant risk to patients from potentially harmful drug interactions.


A comparative study of electric toothbrushes for the effectiveness of plaque removal in relation to toothbrushing duration. Timerstudy.
The purpose of the present study was to test the plaque-removing efficacy of 4 different toothbrushes in relation to duration of toothbrushing. The brushes studied were a manual toothbrush (M), a conventional electric toothbrush--the Blend-a-Dent (BL), the Interplak (IP) and the Braun Plak Control (BPC). For this study, 20 subjects were selected. The study was divided into 5 experiments which differed only in respect to the brushing time. The available time in experiment 1 through 5 was 7.5, 15, 30, 45, 90 s per quadrant respectively. Prior to each experiment, all subjects were asked to abstain from oral hygiene procedures for at least 24 h. The efficacy of toothbrushing in each experiment was studied while one investigator (MAL) brushed the teeth of the subjects. In each subject, all 4 brushes were tested. Each brush was assigned to a quadrant in a random order. No toothpaste was used throughout this study. The amount of dental plaque was evaluated before and after brushing by means of the Silness & Löe plaque index at 6 sites around each tooth investigated. The results show an increase in efficacy for all brushes varying from 7.5 s per quadrant to 90 s per quadrant (mean plaque reduction in terms of percentage 7.5 s-90 s: M = 40%-75%, BL = 45%-82%, BPC = 51%-94%, IP = 64%-92%). The IP removed significantly more plaque than the other 3 after 7.5 s of brushing. From 15 s through 90 s, the IP and BPC were equally effective.(ABSTRACT TRUNCATED AT 250 WORDS)


Molecular Epidemiological Characterization of Methicillin-Susceptible and -Resistant Staphylococcus aureus Isolated from Skin and Soft Tissue Infections in Bangladesh.
Genetic background and molecular characteristics of Staphylococcus aureus collected from patients with skin and soft tissue infections were studied in the North-Central region of Bangladesh from 2015 to 2016. Among 430 clinical isolates, methicillin-resistant S. aureus (MRSA) accounted for 31% having SCCmec type IV (73%) and V (14%), and belonged mostly to coagulase (coa) genotypes IIa, IIIa, IVb, and XIa, while dominant coa type in methicillin-susceptible S. aureus (MSSA) was IIIa, followed by Va, IIa, and VIa. Panton-Valentine Leukocidin genes (pvl) were detected at higher rate in MSSA (54%) than in MRSA (24%). Based on multilocus sequence typing, pvl-positive MRSA isolates were classified into clonal complex 88 (CC88) (ST88, ST2884, ST4345), CC6 (ST6, ST4350), and CC1 (ST1, ST772), while pvl-negative MRSA into CC5, CC22, CC80, CC121, and CC672. The pvl-negative ST80 MRSA isolates had SCCmec-IVa (agr-III/coa-XIc, etd/edinB-positive, fusB-negative), indicating that they belong to the novel CC80 clade related to the European community-acquired MRSA clone. Among MSSA, genotypes ST121/spa-t645/coa-Va and ST2884 (CC88)/spa-t2393/coa-IIIa were identified in both pvl-positive and negative isolates, and all the ST772 isolates harbored pvl. All the ST121 isolates had a variant of elastin-binding protein gene (ebpS-v) with internal 180-nucleotide deletion. The present study suggested that CC88 (ST88, ST2884) and ST772 are the putative dominant lineages of pvl-positive MRSA/MSSA, while novel CC80 clade is one of the main pvl-negative MRSA lineages distributed endemically in Bangladesh.


Arginine vasopressin-stimulated insulin secretion and elevation of intracellular Ca++ concentration in rat insulinoma cells: influences of a phospholipase C inhibitor 1-[6-[[17 beta-methoxyestra-1,3,5(10)-trien- 17-yl]amino]hexyl]-1H-pyrrole-2,5-dione (U-73122) and a phospholipase A2 inhibitor N-(p-amylcinnamoyl)anthranilic acid.
The present study investigated the mechanism by which arginine vasopressin (AVP) increases insulin secretion in rat insulinoma (RINm5F) cells by using a specific phospholipase C (PLC) inhibitor, 1-[6-[[17 beta-3-methoxyestra-1,3,5(10)-trien-17- yl]amino]hexyl]-1H-pyrrole-2,5-dione (U-73122), and a phospholipase A2 (PLA2) inhibitor, N-(p-amylcinnamoyl)anthranilic acid (ACA). AVP (0.1-100 nM) increased insulin secretion and cytosolic free Ca++ concentration ([Ca++]i) dose-dependently. AVP-induced increases in the intracellular concentration of inositol 1,4,5-trisphosphate (IP3) and [Ca++]i were dose-dependently inhibited by U-73122 (2-8 microM). At 8 microM, U-73122 abolished AVP's effect on IP3 and [Ca++]i, but AVP-induced increases in insulin secretion were only reduced by 35%. In contrast, 8 microM U-73122 did not reduce the ionomycin (a Ca++ ionophore, 100 nM)-induced increase in [Ca++]i. The discrepancy between the results of [Ca++]i and insulin secretion in U-73122 experiments is indicative of the multiple signal transduction pathways associated with the activation of AVP receptors, specifically the Ca(++)-independent pathway. The phospholipase A2 inhibitor ACA (100 microM) did not antagonize AVP (10 nM)-induced increases in insulin secretion. These results suggested: 1) U-73122 blocks PLC activities but fails to block other signal transduction pathways that trigger insulin secretion in these cells and 2) AVP increases insulin release from RINm5F cells through both the PLC-mediated Ca(++)-dependent and Ca(++)-independent pathways.


Ventilator-associated pneumonia in neonates: the role of point of care lung ultrasound.
No consensus exists regarding the definition of ventilator-associated pneumonia (VAP) in neonates and reliability of chest X-ray (CXR) is low. Lung ultrasound (LU) is a potential alternative diagnostic tool. The aim was to define characteristics of VAP in our patient population and propose a multiparameter score, incorporating LU, for VAP diagnosis. Between March 25, 2018, and May 25, 2019, infants with VAP were identified. Clinical, laboratory and microbiology data were collected. CXRs and LU scans were reviewed. A multiparameter VAP score, including LU, was calculated on Day 1 and Day 3 for infants with VAP and for a control group and compared with CXR. VAP incidence was 10.47 episodes/1000 ventilator days. LU and CXR were available for 31 episodes in 21 infants with VAP, and for six episodes in five patients without VAP. On Day 1, a VAP score of > 4, and on Day 3 a score of > 5 showed sensitivity of 0.94, and area under the curve of 0.91 and 0.97, respectively. AUC for clinical information only was 0.88 and for clinical and CXR 0.85.Conclusion: The multiparameter VAP score including LU could be useful in diagnosing VAP in neonates with underlying lung pathology. What is Known: • Ventilator associated pneumonia (VAP) is common in infants on the neonatal unit and is associated with increased use of antibiotics, prolonged ventilation and higher incidence of chronic lung disease. • Commonly used definitions of VAP are difficult to apply in neonates and interpretation of chest X-ray is challenging with poor inter-rater agreement in patients with underlying chronic lung disease. What is New: • The multiparameter VAP score combining clinical, microbiology and lung ultrasound (LU) data is predictive for VAP diagnosis in preterm infants with chronic lung disease. • LU findings of VAP in neonates showed high inter-rater agreement and included consolidated lung areas, dynamic bronchograms and pleural effusion.


Survivability of Clostridioides difficile spores in fermented pork summer sausage during refrigerated storage.
Clostridioides difficile is a spore-forming pathogen that causes serious enteric disease in humans. Strains have been isolated from food animals and meat, including pork, which suggest a potential for foodborne transmission. Pork summer sausage is a popular fermented meat product, which is consumed cooked or cooked to a lower internal temperature due to acidification of the product. The effect of acidity and cooking on the viability of C. difficile spores in a fermented meat product has not been determined. Therefore, the aim was to study the survivability of C. difficile spores in fermented pork summer sausage. Fermented pork sausages were prepared according to a commercial recipe with or without starter culture and C. difficile spores followed by fermentation at 37°C for ~12 h under 85% relative humidity until pH 5.0 was reached and further processed as cooked (>57°C) or uncooked (≤57°C) and stored at 4°C. C. difficile spores in sausages were enumerated at 1 h following inoculation and on days 0, 1, 7, 14, 21, 30, 60, and 90 of storage. It was observed that C. difficile spore viability in control unfermented treatment was significantly different on day 0 from the fermented, fermented cooked, and control unfermented cooked treatments (p<0.05); however, there was no significant difference among the latter three treatment groups throughout 90 days of storage (p>0.05). On day 90 of storage, the unfermented control sausages yielded ~4.0 log colony-forming unit (CFU)/g of C. difficile spores compared to ~3.5 log CFU/g recovered from fermented samples and the unfermented cooked control samples identifying spore viability in all treatment groups. C. difficile spores were found to survive the acidity and cooking of fermented pork summer sausage and storage at 4°C for 3 months, thereby highlighting the need for effective intervention strategies to reduce the risk of C. difficile contamination in pork products.