Role of urinary concentrating ability in the generation of toxic papillary necrosis.
We studied the pathogenesis of chemically induced papillary necrosis in six groups of rats. Papillary necrosis was produced by a single injection of 2-bromoethylamine hydrobromide (BEA), 50 mg, i.v.; the animals were followed for 7 to 10 days after the administration of the compound. Following BEA, heterozygous Brattleboro rats developed all the functional and morphologic lesions of papillary necrosis that we previously described in Sprague-Dawley rats. They were unable to maintain sodium balance when dietary sodium was withdrawn. Homozygous Brattleboro rats, on the other hand, developed none of the manifestations of papillary necrosis (that is, animals with central diabetes insipidus were protected completely from the nephrotoxic effects of BEA). They adapted normally to a zero sodium diet. Chronic administration of vasopressin to homozygous Brattleboro rats fully restored the toxic effects of BEA. Lowering urinary concentrating ability by inducing a water diuresis in Sprague-Dawley rats completely protected against BEA-induced papillary necrosis. Decreasing papillary solute concentration by furosemide or increasing urine flow after abrupt withdrawal of vasopressin to homozygous Brattleboro rats did not protect against BEA-induced papillary necrosis. We conclude that the combination, but not either alone, of increased urine flow and decreased papillary solute concentration protects against the development of BEA-induced papillary necrosis.


IgG subclass staining in renal biopsies with membranous glomerulonephritis indicates subclass switch during disease progression.
Recent breakthrough findings revealed that most patients with idiopathic (primary) membranous glomerulonephritis have IgG4 antibodies to the phospholipase A2 receptor (PLA2R). These IgG4 antibodies can be detected in the glomerular immune complexes and they colocalize with PLA2R. In secondary forms of membranous glomerulonephritis, such IgG4 antibodies are absent or less prevalent. There are no studies addressing the IgG subclass distribution across different stages of membranous glomerulonephritis. During a 25-month period, we identified 157 consecutive biopsies with membranous glomerulonephritis with adequate tissue for light, immunofluorescence and electron microscopy. Of the 157 membranous glomerulonephritis cases, 114 were primary membranous glomerulonephritis and 43 were secondary membranous glomerulonephritis. We compared the intensity of IgG subclass staining (on a semiquantitative scale of 0 to 3+) and the IgG subclass dominance between primary and secondary membranous glomerulonephritis and between the different stages of membranous glomerulonephritis. In primary membranous glomerulonephritis most (76% of cases) were IgG4 dominant. In contrast, in secondary membranous glomerulonephritis IgG1 was dominant in 60% of biopsies (P=0.0018). Interestingly, in early stage (stage 1) primary membranous glomerulonephritis, IgG1 was the dominant IgG subclass (64% of cases); in all later stages IgG4 dominated (P=0.0493). It appears that there is an inverse relationship between the intensity of glomerular capillary IgG4 and C1q staining. In secondary forms of membranous glomerulonephritis (heterogeneous group with low case numbers), we did not find such associations. Our data indicate that in early stage membranous glomerulonephritis, antibody response is different from later stages, with IgG1 dominant deposits. It is possible that early on, antigens other than PLA2R have an important role, Alternately, there may be an IgG subclass switch in the antibody response with IgG4 taking over later as the dominant immunoglobulin.


Pore-scale model and dewatering performance of municipal sludge by ultrahigh pressurized electro-dewatering with constant voltage gradient.
The disposal of huge municipal sludge with high moisture content has led to numerous energy consumption and brought extensive concerns in the world. In this paper, three dewatering modes, ultrahigh-pressure mechanical dewatering mode (UMDW), pressurized electro-dewatering (PEDW) with constant voltage mode (U-PEDW) and constant voltage gradient mode (G-PEDW) were performed on a self-designed pressurized electro-dewatering apparatus for municipal sludge. The pore structures and moisture distributions were detected by low-field nuclear magnetic resonance technology. Meanwhile, the moisture distributions and quantitative bound strength were analyzed by the thermogravimetric differential scanning calorimetry test. Moreover, a pore-scale electro-osmosis model was accordingly developed based on the fractal characteristics of pore size distribution. Finally, the effect of dewatering modes and operating parameters on moisture content and energy consumption were examined in detail. The results indicate that the pore-scale electro-osmosis model show good consistency with experimental data. The electric field can drive the middle-layers-water to overcome the capillary pressure, and make G-PEDW removing more water than UMDW. The moisture content of dewatered municipal sludge by G-PEDW and U-PEDW reaches to 28.41% and 27.33%, respectively. Furthermore, the energy consumption of G-PEDW is 189.62Wh/kg.H2O, it is much lower than that of U-PEDW. Therefore, the G-PEDW mode with low moisture content and less energy consumption indicates best dewatering performance compared with UMDW and U-PEDW modes. The present work is helpful to understand the dewatering mechanisms of G-PEDW and provides useful guidelines for G-PEDW dewatering technology.


Induction of therapeutic levels of HbF in genome-edited primary β0 39-thalassaemia haematopoietic stem and progenitor cells.
Hereditary persistence of fetal haemoglobin (HPFH) is the major modifier of the clinical severity of β-thalassaemia. The homozygous mutation c.-196 C>T in the Aγ-globin (HBG1) promoter, which causes Sardinian δβ0 -thalassaemia, is able to completely rescue the β-major thalassaemia phenotype caused by the β0 39-thalassaemia mutation, ensuring high levels of fetal haemoglobin synthesis during adulthood. Here, we describe a CRISPR/Cas9 genome-editing approach, combined with the non-homologous end joining (NHEJ) pathway repair, aimed at reproducing the effects of this naturally occurring HPFH mutation in both HBG promoters. After selecting the most efficient guide RNA in K562 cells, we edited the HBG promoters in human umbilical cord blood-derived erythroid progenitor 2 cells (HUDEP-2) and in haematopoietic stem and progenitor cells (HSPCs) from β0 -thalassaemia patients to assess the therapeutic potential of HbF induction. Our results indicate that small deletions targeting the -196-promoter region restore high levels of fetal haemoglobin (HbF) synthesis in all cell types tested. In pools of HSPCs derived from homozygous β0 39-thalassaemia patients, a 20% editing determined a parallel 20% increase of HbF compared to unedited pools. These results suggest that editing the region of HBG promoters around the -196 position has the potential to induce therapeutic levels of HbF in patients with most types of β-thalassaemia irrespective of the β-globin gene (HBB) mutations.


A cyclic AMP mechanism mediates the serotonin-induced increase in glutamic acid decarboxylase activity in the preoptic area and hypothalamus.
Previous studies have shown that the injection of 5-hydroxytryptamine (5-HT) into the third ventricle of rats on the afternoon of proestrus increases glutamic acid decarboxylase (GAD) activity in the preoptic area and the hypothalamus. In the present report we examine the adenylate cyclase-cyclic AMP (cAMP) system as mediator of that effect. The increase in GAD activity induced by intraventricular injection of 5-HT was completely blocked by injecting an antiserum against cAMP into the third ventricle 30 min earlier, whereas an injection of serum from normal rabbits was ineffective. On the contrary, activation of adenylate cyclase activity by intraventricular injection of forskolin increased GAD activity, an effect that was also blocked by anti-cAMP serum. Anti-cAMP serum also lowered GAD activity in the preoptic area and hypothalamus when injected on the morning of proestrus but not when injected in the afternoon, when the values of GAD activity were already low. The results suggest that a cAMP mechanism may be involved in the changes in preoptic-area and hypothalamic GAD activity such as the rise in enzyme activity induced by intraventricular injection of 5-HT.


Behavioural and anatomical effects of systemically administered leukemia inhibitory factor in the SOD1(G93A G1H) mouse model of familial amyotrophic lateral sclerosis.
We investigated the anatomical and behavioural effects of daily intraperitoneal injection of 25 microg/kg of LIF in the SOD1(G93A G1H) mouse model of familial ALS. We found some subtle beneficial behavioural changes in LIF treated mice. These included later onset of clinical disease in females as determined by clinical scoring; better grip strength in males; and delayed development of motor impairment in males as determined by the rotarod test. However, we found no significant rescue of motoneurons or prolongation of survival as a result of this systemic dose of LIF in these mice.


Pharmacokinetic evaluation of Sinisan containing vinegar-processed products in depressive rats, a comprehensive perspective of 'individual herb, herb-pair, and herbal formula'.
As a classical formula for the treatment of depression, the clinical application of vinegar-processed products of Bupleuri Radix (Bupleurum chinense DC., BR) and Paeoniae Radix Alba (Paeonia lactiflora Pall., PRA) contained in Sinisan (SNS) is still controversial. Three levels of 'individual herb, herb-pair, and herbal formula' were employed to investigate whether and how the processing of main drugs affected the active constituents of pharmacokinetics in SNS, as well as their impacts on the hepatic CYP450 enzyme. Rats were subjected to construct a chronic unpredictable mild stimulation (CUMS) model. A rapid and sensitive ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS/MS) analytical method was developed and validated for simultaneously quantitative evaluation of thirteen potential active compounds of SNS in depressive rat plasma, and successfully applied to a holistic comparison of pharmacokinetics. The differences in pharmacokinetic parameters based on three different forms of drug composition from BR and PRA before and after vinegar-processing were compared. Meanwhile, qRT-PCR and Western Blot were utilized to explore the metabolic activity of three isoforms of CYP450 enzyme scattered in the livers of depressive rats. The characteristic pharmacokinetics profiles of thirteen representative constituents in CUMS rats were influenced by vinegar-processing of BR and PRA and/or the compatibility. In detail, there were significant differences in the Cmax, AUC0-24, AUC0-∞, t1/2, and MRT0-24 of most constituents among the three different forms of drug composition from BR and PRA before and after vinegar-processing, with the most obvious changes in six constituents from the adjuvant and mediating guide drugs. And also, the pharmacokinetic parameters of seven constituents from BR and PRA in SNS containing vinegar-processed products obviously changed after compatibility. Additionally, the mRNA and protein levels of CYP1A2, CYP2E1, and CYP3A1 were observed to increase significantly with the processing of BR and PRA and the combination/formulation. In conclusion, SNS containing vinegar-processed products was more conducive to the absorption of most activated constituents compared to the original formula in vivo. The vinegar-processing of BR and PRA and the compatibility co-contribute to the pharmacokinetic variability of active compounds of SNS in CUMS rats, and the extent of contribution varies among drugs, which might be related to the regulation of the hepatic drug metabolizing enzymes. The finding of the investigation could help to better understand how active compounds metabolized in vivo, which might be helpful for guiding the clinical application of SNS containing vinegar-processed products.


Cyclical dermal micro-niche switching governs the morphological infradian rhythm of mouse zigzag hair.
Biological rhythms are involved in almost all types of biological processes, not only physiological processes but also morphogenesis. Currently, how periodic morphological patterns of tissues/organs in multicellular organisms form is not fully understood. Here, using mouse zigzag hair, which has 3 bends, we found that a change in the combination of hair progenitors and their micro-niche and subsequent bend formation occur every three days. Chimeric loss-of-function and gain-of-function of Ptn and Aff3, which are upregulated immediately before bend formation, resulted in defects in the downward movement of the micro-niche and the rhythm of bend formation in an in vivo hair reconstitution assay. Our study demonstrates the periodic change in the combination between progenitors and micro-niche, which is vital for the unique infradian rhythm.


Evolution of elastin structure.
The aortae of a number of vertebrates and invertebrates were tested for the presence of elastin to determine when this protein first appears phylogenetically. Using several criteria, including amino acid composition, presence of desmosines, and histological characteristics, we found that all representative vertebrate groups have elastin except the primitive jawless fishes (lampreys and hagfishes). All the invertebrates tested, representing most major phyla, were found lackin in elastin as well. Comparison of purified elastins from several vertebrate groups reveals some striking differences in their amino acid compositions and properties, including the arrangement of the elastic fibers in the aorta. The patterns of variations in amino acid composition suggest a mode of evolution which is different from the slow accumulation of point mutations observed with globular proteins.


Vehicular traffic noise prediction and propagation modelling using neural networks and geospatial information system.
This study proposes a neural network (NN) model to predict and simulate the propagation of vehicular traffic noise in a dense residential area at the New Klang Valley Expressway (NKVE) in Shah Alam, Malaysia. The proposed model comprises of two main simulation steps: that is, the prediction of vehicular traffic noise using NN and the simulation of the propagation of traffic noise emission using a mathematical model. First, the NN model was developed with the following selected noise predictors: the number of motorbikes, the sum of vehicles, car ratio, heavy vehicle ratio (e.g. truck, lorry and bus), highway density and a light detection and ranging (LiDAR)-derived digital surface model (DSM). Subsequently, NN and its hyperparameters were optimised by a systematic optimisation procedure based on a grid search approach. The noise propagation model was then developed in a geographic information system (GIS) using five variables, namely road geometry, barriers, distance, interaction of air particles and weather parameters. The noise measurement was conducted continuously at 15-min intervals and the data were analysed by taking the minimum, maximum and average values recorded during the day. The measurement was performed four times a day (i.e. morning, afternoon, evening, and midnight) over two days of the week (i.e. Sunday and Monday). An optimal radial basis function NN was used with 17 hidden layers. The learning rate and momentum values were 0.05 and 0.9, respectively. Finally, the accuracy of the proposed method achieved 78.4% with less than 4.02 dB (A) error in noise prediction. Overall, the proposed models were found to be promising tools for traffic noise assessment in dense urban areas.


A necroptosis-related gene signature for predicting prognosis, immune landscape, and drug sensitivity in hepatocellular carcinoma.
Hepatocellular carcinoma (HCC) remains a growing threat to global health. Necroptosis is a newly discovered form of cell necrosis that plays a vital role in cancer development. Thus, we conducted this study to identify a predictive signature of HCC based on necroptosis-related genes. The tumor samples in the liver hepatocellular carcinoma (LIHC) cohort from The Cancer Genome Atlas (TCGA) database were subtyped using the consensus clustering algorithm. Univariate Cox regression and LASSO-Cox analysis were performed to identify a gene signature from genes differentially expressed between tumor clusters. Then, we integrated the TNM stage and the prognostic model to build a nomogram. The gene signature and the nomogram were externally validated in the GSE14520 cohort from the Gene Expression Omnibus (GEO) and the LIRP-JP cohort from the International Cancer Genome Consortium (ICGC). Evaluations of predictive performance evaluations were conducted using Kaplan-Meier plots, time-dependent receiver operating characteristic curves, principal component analyses, concordance indices, and decision curve analyses. The tumor microenvironment was estimated using eight published methods. Finally, we forecasted the sensitivity of HCC patients to immunotherapy and chemotherapy based on this gene signature. We identified two necroptosis-related clusters and a 10-gene signature (MTMR2, CDCA8, S100A9, ANXA10, G6PD, SLC1A5, SLC2A1, SPP1, PLOD2, and MMP1). The gene signature and the nomogram had good predictive ability in the TCGA, ICGC, and GEO cohorts. The risk score was positively associated with the levels of necroptosis and immune cell infiltrations (especially of immunosuppressive cells). The high-risk group could benefit more from immunotherapy and some chemotherapeutics than the low-risk group. The necroptosis-related gene signature provides a new method for the risk stratification and treatment optimization of HCC. The nomogram can further improve predictive accuracy.


Ulinastatin ameliorated streptozotocin-induced diabetic nephropathy: Potential effects via modulating the components of gut-kidney axis and restoring mitochondrial homeostasis.
Growing evidence supports the role of the gut-kidney axis and persistent mitochondrial dysfunction in the pathogenesis of diabetic nephropathy (DN). Ulinastatin (UTI) has a potent anti-inflammatory effect, protecting the kidney and the gut barrier in sepsis, but its effect on DN has yet to be investigated. This study aimed to assess the potential mitigating effect of UTI on DN and investigate the possible involvement of gut-kidney axis and mitochondrial homeostasis in this effect. Forty male Wistar rats were divided equally into four groups: normal; UTI-treated control; untreated DN; and UTI-treated DN. At the end of the experiment, UTI ameliorated DN by modulating the gut-kidney axis as it improved serum and urinary creatinine, urine volume, creatinine clearance, blood urea nitrogen, urinary albumin, intestinal morphology including villus height, crypt depth, and number of goblet cells, with upregulating the expression of intestinal tight-junction protein claudin-1, and counteracting kidney changes as indicated by significantly decreasing glomerular tuft area and periglomerular and peritubular collagen deposition. In addition, it significantly reduced intestinal and renal nuclear factor kappa B (NF-κB), serum Complement 5a (C5a), renal monocyte chemoattractant protein-1 (MCP-1), renal intercellular adhesion molecule 1 (ICAM1), and renal signal transducer and activator of transcription 3 (STAT3), mitochondrial dynamin related protein 1 (Drp1), mitochondrial fission 1 protein (FIS1), mitochondrial reactive oxygen species (ROS), renal hydrogen peroxide (H2O2), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels. Furthermore, it significantly increased serum short chain fatty acids (SCFAs), and mitochondrial ATP levels and mitochondrial transmembrane potential. Moreover, there were significant correlations between measured markers of gut components of the gut-kidney axis and renal function tests in UTI-treated DN group. In conclusion, UTI has a promising therapeutic effect on DN by modulating the gut-kidney axis and improving renal mitochondrial dynamics and redox equilibrium.


Phenotypic non-penetrance in granular corneal dystrophy type II.
To report a possible case of phenotypic non-penetrance in granular corneal dystrophy type II (GCD-II). DNA analysis was performed on 11 patients with white granular corneal opacities and 50 normal controls after informed consent was obtained. The TGFBI gene was analyzed by sequencing DNA from epidermal keratinocytes obtained using adhesive tape. The heterozygous R124H mutation of TGFBI gene was found in all 11 patients. Although 49 normal controls had no mutation in the TGFBI gene, one normal control, a 26-year-old man, had the heterozygous R124H mutation of TGFBI gene. His 55-year-old father had the same mutation, but no corneal opacities. As not all mutations are expressed in the phenotype, GCD-II gene mutation may have non-penetrance. This report documents a possible case of phenotypic non-penetrance in GCD-II.


Effects in rats and guinea pigs of six-month exposures to sulfuric acid mist, ozone, and their combination.
Rats and guinea pigs were exposed to 0.5 ppm O3, 10 mg/m3 sulfuric acid (H2SO4) mist, or their combination for 6 h/d, 5 d/wk for 6 mo. Microscopic alterations were seen in the lungs of guinea pigs exposed to O3 alone or in combination with H2SO4 mist. No other microscopic lesions were present in either rats or guinea pigs. No biologically meaningful synergistic effects were noted in animals exposed to the combination of O3 and H2SO4 mist.


The membrane bound N-terminal domain of human adenosine diphosphate ribosylation factor-1 (ARF1).
The small G protein adenosine diphosphate ribosylation factor-1 (ARF1) is activated by cell membrane binding of a self-folding N-terminal domain. We present a model of the human ARF1 N-terminal peptide in planar lipid bilayers, determined from neutron lamellar diffraction and circular dichroism data with molecular modelling. This amphipathic domain lies at a shallow membrane depth, ideal for regulation of the ARF1 bio-timer by rapid, reversible membrane binding. The helical region does not elongate upon membrane binding, leaving the connecting flexible linker region's length unchanged.


The first true deserticolous species of Buthus Leach, 1815 from Algeria (Scorpiones: Buthidae); Ecological and biogeographic considerations.
Since the early 2000s, the genus Buthus Leach, 1815 (family Buthidae) has been the subject of an important number of studies. These concerned particularly the species belonging to the 'Buthus occitanus' complex. A number of populations previously considered as subspecies or varieties of B. occitanus Leach were raised to the rank of species, but also many new species have been described. Most of the species considered in these studies come from North Africa, in particular from Morocco, Mauritania, Chad, Sudan and Egypt, but only two new species were recorded from Algeria. At present, one more new species of Buthus is described from the Algerian Saharan Desert, raising the number of confirmed Buthus in Algeria to five. Since most Buthus species from North Africa, and in particular those from Algeria, inhabit more mesic environments than the Saharan Central compartment, the new species appears as the first true deserticolous species found in this country.


Peripheral ameloblastic carcinoma: a case report of a rare neoplasm.
An example of a rare peripheral ameloblastic carcinoma of the maxillary tuberosity is presented. A discussion of its possible relationship to the dental lamina and malignant ameloblastoma follows.


Developing mechanical milking in camels? Some main steps to take….
After a first phase of development in the ex-Soviet Union in the 1940s, camel mechanical milking is now developing again in the Arabic peninsula, North and East Africa, Asia, Australia and even in the USA and Europe in a lesser extent, because of the great demand and important health value of camel milk. Nevertheless, such a development remains empirical and uses trial and error methodology, which is generally more time-consuming and more expensive and could create a deadlock in the situation. Nevertheless, developing mechanical milking of camels could be done throughout a step by step well-designed approach rather than this empirical approach. It is the only way to understand the animal/machine interaction and to give us the means to adapt machine milking to the different situations encountered in the world and to animal specificities.After describing the different essential and ancillary steps of this development (knowledge of animal physiology, udder and teat shapes, teat functional characteristics, first functional data of milking including teat reaction, milk emission kinetic, efficiency of milk extraction, weaning procedure, milking procedure, milking behavior of animals, adaptation of material and settings…), we aim to relate, as example, the first results obtained in Tunisian dromedary camels in the last 4 years as basis for more adapted or even specific materials and setting evolution.


Safety and parasite clearance of artemisinin-resistant Plasmodium falciparum infection: A pilot and a randomised volunteer infection study in Australia.
Artemisinin resistance is threatening malaria control. We aimed to develop and test a human model of artemisinin-resistant (ART-R) Plasmodium falciparum to evaluate the efficacy of drugs against ART-R malaria. We conducted 2 sequential phase 1, single-centre, open-label clinical trials at Q-Pharm, Brisbane, Australia, using the induced blood-stage malaria (IBSM) model, whereby healthy participants are intravenously inoculated with blood-stage parasites. In a pilot study, participants were inoculated (Day 0) with approximately 2,800 viable P. falciparum ART-R parasites. In a comparative study, participants were randomised to receive approximately 2,800 viable P. falciparum ART-R (Day 0) or artemisinin-sensitive (ART-S) parasites (Day 1). In both studies, participants were administered a single approximately 2 mg/kg oral dose of artesunate (AS; Day 9). Primary outcomes were safety, ART-R parasite infectivity, and parasite clearance. In the pilot study, 2 participants were enrolled between April 27, 2017, and September 12, 2017, and included in final analyses (males n = 2 [100%], mean age = 26 years [range, 23-28 years]). In the comparative study, 25 participants were enrolled between October 26, 2017, and October 18, 2018, of whom 22 were inoculated and included in final analyses (ART-R infected participants: males n = 7 [53.8%], median age = 22 years [range, 18-40 years]; ART-S infected participants: males n = 5 [55.6%], median age = 28 years [range, 22-35 years]). In both studies, all participants inoculated with ART-R parasites became parasitaemic. A total of 36 adverse events were reported in the pilot study and 277 in the comparative study. Common adverse events in both studies included headache, pyrexia, myalgia, nausea, and chills; none were serious. Seven participants experienced transient severe falls in white cell counts and/or elevations in liver transaminase levels which were considered related to malaria. Additionally, 2 participants developed ventricular extrasystoles that were attributed to unmasking of a predisposition to benign fever-induced tachyarrhythmia. In the comparative study, parasite clearance half-life after AS was significantly longer for ART-R infected participants (n = 13, 6.5 hours; 95% confidence interval [CI] 6.3-6.7 hours) compared with ART-S infected participants (n = 9, 3.2 hours; 95% CI 3.0-3.3 hours; p < 0.001). The main limitation of this study was that the ART-R and ART-S parasite strains did not share the same genetic background. We developed the first (to our knowledge) human model of ART-R malaria. The delayed clearance profile of ART-R parasites after AS aligns with field study observations. Although based on a relatively small sample size, results indicate that this model can be safely used to assess new drugs against ART-R P. falciparum. The studies were registered with the Australian New Zealand Clinical Trials Registry: ACTRN12617000244303 (https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=372357) and ACTRN12617001394336 (https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=373637).


Relationship of thyroid states and serum thrombomodulin (TM) levels in patients with Graves' disease: TM, a possible new marker of the peripheral activity of thyroid hormones.
Thrombomodulin (TM) is a thrombin receptor glycoprotein that functions as an anticoagulant on the surface of endothelial cells. Serum TM is regarded as a new marker of generalized endothelial cell damage. Serum TM concentrations were measured in 75 patients with Graves' disease and 75 age- and sex-matched healthy subjects. Serum TM levels in patients in the hyperthyroid state were significantly increased, while those in patients in the hypothyroid state due to treatment were significantly decreased compared with levels in control subjects. All patients with untreated Graves' disease had markedly elevated TM levels. Serum TM levels correlated closely with thyroid hormone concentration (TM vs. free T4, r = 0.858; P = 0.001). Serial measurement of individual patients revealed that serum TM levels paralleled thyroid hormone concentration, reaching normal control values upon attainment of euthyroidism. On the other hand, there was no significant correlation between serum TM concentration and titer of antithyroglobulin antibodies, titer of antimicrosomal antibodies, serum thyroglobulin level, or goiter size, and serum TM was not directly influenced by TSH receptor antibodies or resting pulse rates. The close correlation between serum TM and thyroid hormone concentration suggests that thyroid hormones might influence the synthesis or metabolism of TM on the surface of endothelial cells in patients with Graves' disease.


Increased long non-coding RNA NORAD reflects serious cardiovascular stenosis, aggravated inflammation status, and higher lipid level in coronary heart disease.
Long non-coding RNA activated by DNA damage (lnc-NORAD) modulates inflammation, lipid level, and atherosclerosis in various cardiovascular diseases. This study intended to investigate the dysregulated expression of lnc-NORAD, and its linkage with clinical characteristics, inflammatory cytokines, and accumulating major adverse cardiovascular events (MACE) in coronary heart disease (CHD) patients. Totally, 160 CHD patients, 30 disease controls (DCs), and 30 healthy controls (HCs) were included. The reverse transcription-quantitative polymerase chain reaction was used to detect lnc-NORAD expression in peripheral blood mononuclear cell samples from all participants. Enzyme-linked immunosorbent assay was applied to detect proinflammatory cytokines and adhesion molecules in CHD patients. Then, MACE was recorded during a median follow-up of 12 (range: 1.0-27.0) months. Lnc-NORAD was highest in CHD patients, followed by DCs, and lowest in HCs (p < 0.001). In CHD patients, lnc-NORAD was positively linked with Gensini score (p = 0.001). Meanwhile, lnc-NORAD was positively linked to C-reactive protein (p = 0.023), tumor necrosis factor-alpha (p = 0.016), interleukin (IL)-6 (p = 0.003), IL-8 (P = 0.018), and IL-17A (p = 0.029). No relation of lnc-NORAD with vascular cell adhesion molecule-1 (p = 0.094) and intercellular adhesion molecule-1 (p = 0.060) was found. Furthermore, lnc-NORAD was positively related to total cholesterol (p = 0.014) and low-density lipoprotein cholesterol (p = 0.004), whereas lnc-NORAD was not linked to triglyceride (p = 0.103) and high-density lipoprotein cholesterol (p = 0.533). However, lnc-NORAD (high vs. low), and its higher quartiles were both not linked to accumulating MACE rate (p > 0.05). Increased lnc-NORAD is linked with aggravated stenosis degree, inflammation status, and blood lipid in CHD patients. However, further validation is required.


Breast cancer screening: should it be introduced and how?
This brief discussion of the papers by Gästrin and Paccaud is looking at differences in the results of different study types. Introducing screening means changing unsystematic to systematic screening: only the latter has been shown to be effective. The comparison between randomized trials, and follow-up of acceptors only, suggests that the non-acceptors have much higher risks. Programmes should therefore concentrate on trying to reach non-acceptors. The combination of mammographic screening and self-examination in a randomized trial could add to the existing evidence.


Through the looking glass: good looks and dignity in care.
There are roughly two meanings attached to the concept of dignity: humanitas and dignitas. Humanitas refers to ethical and juridical notions of equality, autonomy and freedom. Much less understood is the meaning of dignitas, which this paper develops as peoples' engagement with aesthetic values and genres, and hence with differences between people. Departing from a critical reading of Georgio Agamben's notion of 'bare life', I will analyze a case where aesthetics are quite literally at stake: women who lost their hair due to cancer treatment. The analysis shows a complicated interplay between varying evaluations of female baldness by the self and others, mediated by (often strongly negative) cultural imaginaries, and aesthetic genres depicting conventional ways of 'looking good'. The paper concludes by arguing for a reconnection of the two notions of dignity, and for a rehabilitation of aesthetics in daily life and care as fundamental values for organizing our societies.


Patient education in asthmatic children.
The major goal of all diagnostic and therapeutic efforts in childhood asthma is to prevent progression of lung disease into adulthood. To improve the uncomfortable situation of underdiagnosis and undertreatment and to lower the risk of acquiring irreversible lung damage, an optimal co-working relationship between family doctor and parents, and a patient education program toward that end, is essential.


The not-so-sweet side of sugar: Influence of the microenvironment on the processes that unleash cancer.
The role of "aerobic glycolysis" in cancer has been examined often in the past. Results from those studies, most of which were performed on two dimensional conditions (2D, tissue culture plastic), demonstrate that aerobic glycolysis occurs as a consequence of oncogenic events. These oncogenic events often drive malignant cell growth and survival. Although 2D based experiments are useful in elucidating the molecular mechanisms of oncogenesis, they fail to take contributions of the extracellular microenvironment into account. Indeed we, and others, have shown that the cellular microenvironment is essential in regulating processes that induce and/or suppress the malignant phenotype/properties. This regulation between the cell and its microenvironment is both dynamic and reciprocal and involves the integration of cellular signaling networks in the right context. Therefore, given our previous demonstration of the effect of the microenvironment including tissue architecture and media composition on gene expression and the integration of signaling events observed in three-dimension (3D), we hypothesized that glucose uptake and metabolism must also be essential components of the tissue's signal "integration plan" - that is, if uptake and metabolism of glucose were hyperactivated, the canonical oncogenic pathways should also be similarly activated. This hypothesis, if proven true, suggests that direct inhibition of glucose metabolism in cancer cells should either suppress or revert the malignant phenotype in 3D. Here, we review the up-to-date progress that has been made towards understanding the role that glucose metabolism plays in oncogenesis and re-establishing basally polarized acini in malignant human breast cells.


Novel missense variants in PCK1 gene cause cytosolic PEPCK deficiency with growth failure from inadequate caloric intake.
Cytosolic PEPCK deficiency (PCKDC) is a rare autosomal recessive inborn error of metabolism, which can present with hypoglycemia, lactic acidosis, and liver failure. It is caused by biallelic pathogenic variants in the PCK1 gene. Only four PCK1 variants have been previously reported in seven patients with PCKDC, and their clinical course of this condition has not been well characterized. Here, we report a Hispanic male with novel biallelic PCK1 variants, p.(Gly430Asp) and p.(His496Gln), who had a unique clinical presentation. He presented with a new onset of growth failure, elevated blood lactate, transaminitis, and abnormal urine metabolites profile, but he has not had documented hypoglycemia. Growth restriction happened due to insufficient caloric intake, and it was improved with nutritional intervention. PCKDC is a manageable disorder and therefore appropriate nutritional and clinical suspicion from typical lab abnormalities which lead to molecular confirmation tests are essential to prevent poor clinical outcomes.


Stimulation of endogenous dopamine release and metabolism in amphibian retina by light- and K+-evoked depolarization.
The release and metabolism of dopamine (DA) in retina was assessed using an in vitro eye cup preparation of the African clawed frog. The concentration of DA in the incubation medium and of 3,4-dihydroxyphenylacetic acid (DOPAC) and DA in retinas was measured by high-performance liquid chromatography with electrochemical detection (HPLC-ED). K+-induced depolarization stimulated DA overflow from the eye cups into the incubation medium and increased tissue DOPAC levels in dark-adapted retinas. Basal and K+-stimulated DA overflow and DOPAC accumulation were Ca2+-dependent. Exposure of dark-adapted retinas to constant white light for 1 h also increased DA overflow and DOPAC levels, while 1 h of alternating 10 s periods of light and dark had no effect. The results indicate that DA release and metabolism may be stimulated as a function of light-adaptation.


[Antimicrobial stewardship programme implementation in a medical ward].
Antimicrobial stewardship programmes (ASP) have proven to be effective tools for reducing the use of antimicrobials. The purpose of the study is to evaluate the effect of an ASP implantation in a medical Ward. Prospective intervention study in a medical ward with a heterogeneous composition. In September 2014, an ASP based on prospective audits was implemented. Antimicrobial consumption and the length of stay and mortality in all patients admitted, as well as in the main infections present in the unit, were compared before and after two years of the ASP implementation. A total of 378 infectious episodes of 335 pa-tients were evaluated in 168 meetings. The prescriber ac-cepted 92.3% of the suggestions. The consumption of an-timicrobials reviewed was reduced from 31.3 to 17.6 DDD / 100-stays (β =-0.40, P = 0.015). The average cost per income was reduced from € 161.4 to € 123.3 (-23.6%). No differences were found in total length of stay or mortality. There were no changes in the incidence of Clostridium difficile infection or candidemia between the two periods. There were no significant differences in length of stay or mortality in total bacteremia, candidemia, and urinary tract infections caused by multiresistant bacteria. The implementation of an ASP in a heterogeneous medical ward significantly reduces the use of antimicrobials in a short time horizon without adversely affecting the evolution of the patients..


Involvement of gastrointestinal mechano- and intestinal chemoreceptors in vagal reflexes: an electrophysiological study.
The role of gastrointestinal mechanoreceptors and intestinal chemoreceptors in the genesis of vago-vagal reflexes was assessed by recording single vagal efferent fibre discharge in the urethane-anaesthetized ferret during procedures known to activate discrete populations of gastrointestinal afferent fibres. Distension of the stomach, duodenum and jejunum was used to activate mechanoreceptors while perfusion of the intestinal loops with various chemical solutions was used to activate mucosal chemoreceptors. Mechanical stimulation of the stomach and/or intestine was effective in modulating vagal efferent discharge in 90% of units tested. The response (either excitation or inhibition of efferent firing) was characterized by its short-latency (less than 1 s), slow-adaptation, and rapid return on removal of the stimulus. In contrast, chemical stimulation was much less potent evoking clear-cut responses in only 26 of the 109 efferent units. Luminal HCl was the most effective stimulus accounting for 81% of the efferent responses although these were of long-latency (greater than 1 min), gradual in onset and poorly maintained. Other efferent responses to HCl and hypertonic saline were characterized by a long-latency, sudden increase in discharge associated with the prodrome of vomiting. We conclude that while the mechanosensitive afferent input is well represented in terms of the genesis of vagal reflexes, the chemosensitive afferent input may be more important in behavioural aspects of visceral stimuli like vomiting.


Molecular magnetic resonance imaging of the genitourinary tract: recent results and future directions.
This article focuses on preclinical and early clinical applications of renal cell MR imaging, on new developments in MR control of intrarenal gene therapy, and on several potential applications of molecular imaging techniques, mainly targeting cell receptors and enzyme activity, which could find exciting applications within the genitourinary tract.


Endoscopic ultrasound-guided transmural drainage of walled-off pancreatic necrosis in patients with portal hypertension and intra-abdominal collaterals.
Acute necrotizing pancreatitis (ANP) is complicated with segmental portal hypertension (PHT) and formation of venous collaterals. Presence of collaterals in vicinity of endoscopic transmural tract can lead to potentially catastrophic situation. Here, we report safety and outcome of EUS-guided transmural drainage of walled-off pancreatic necrosis (WOPN) in patients with PHT and intra-abdominal collaterals. Retrospective analysis of collected database of patients (n=18; age 40.94±8.43 years; 17 males) who underwent EUS-guided transmural drainage of WOPN and had PHT with collaterals. Etiology of ANP: alcohol in 14 and gallstones in 3 patients. Mean size of collection was 10.7±3.5 cm, and all 18 patients had splenic vein thrombosis with 1 patient also having portal vein thrombosis. Drainage was not feasible in 1 patient as no window free of collaterals could be found. One patient with gastric variceal bleeding underwent drainage after successful obliteration of varix with glue. Multiple plastic stents were placed in 15 patients and fully covered self-expanding metallic stent (FCSEMS) in 1 patient and 1 patient required direct endoscopic necrosectomy (DEN). Mean procedures required were 3 ± 0.79 and time to resolution was 4.4 ± 1.3 weeks. One patient had post-drainage bleeding that was successfully managed with intravenous terlipressin and intermittent irrigation via nasocystic catheter. Successfully treated patients have been asymptomatic over follow up period of 15.65±12.2 weeks. EUS-guided drainage of WOPN seems to be safe and effective in patients with portal hypertension and intra-abdominal collaterals.


Proteomic analysis links alterations of bioenergetics, mitochondria-ER interactions and proteostasis in hippocampal astrocytes from 3xTg-AD mice.
The pathogenesis of Alzheimer's disease (AD), a slowly-developing age-related neurodegenerative disorder, is a result of the action of multiple factors including deregulation of Ca2+ homeostasis, mitochondrial dysfunction, and dysproteostasis. Interaction of these factors in astrocytes, principal homeostatic cells in the central nervous system, is still poorly understood. Here we report that in immortalized hippocampal astrocytes from 3xTg-AD mice (3Tg-iAstro cells) bioenergetics is impaired, including reduced glycolysis and mitochondrial oxygen consumption, and increased production of reactive oxygen species. Shotgun proteomics analysis of mitochondria-ER-enriched fraction showed no alterations in the expression of mitochondrial and OxPhos proteins, while those related to the ER functions and protein synthesis were deregulated. Using ER- and mitochondria-targeted aequorin-based Ca2+ probe we show that, in 3Tg-iAstro cells, ER was overloaded with Ca2+ while Ca2+ uptake by mitochondria upon ATP stimulation was reduced. This was accompanied by the increase in short distance (≈8-10 nm) contact area between mitochondria and ER, upregulation of ER-stress/unfolded protein response genes Atf4, Atf6 and Herp, and reduction of global protein synthesis rate. We suggest that familial AD mutations in 3Tg-iAstro cells induce mitochondria-ER interaction changes that deregulate astrocytic bioenergetics, Ca2+ homeostasis and proteostasis. These factors may interact, creating a pathogenic loop compromising homeostatic and defensive functions of astroglial cells predisposing neurons to dysfunction.


Cause and effect in epigenetics - where lies the truth, and how can experiments reveal it?: Epigenetic self-reinforcing loops obscure causation in cancer and aging.
Epigenetic changes are implicated in aging and cancer. Sometimes, it is clear whether the causing agent of the condition is a genetic factor or epigenetic. In other cases, the causative factor is unclear, and could be either genetic or epigenetic. Is there a general role for epigenetic changes in cancer and aging? Here, I present the paradigm of causative roles executed by epigenetic changes. I discuss cases with clear roles of the epigenome in cancer and aging, and other cases showing involvement of other factors. I also present the possibility that sometimes causality is difficult to assign because of the presence of self-reinforcing loops in epigenetic regulation. Such loops hinder the identification of the causative factor. I provide an experimental framework by which the role of the epigenome can be examined in a better setting and where the presence of such loops could be investigated in more detail.


Mobile learning in nursing education: A bibliometric analysis and visualization.
This study performed a bibliometric analysis of studies related to mobile learning in the field of nursing education. The Scopus database was used to determine the most frequently cited studies on mobile learning in nursing education. VOSviewer and Bibliometrix were employed for bibliometric analysis and visualization. Science mapping and performance analysis was adopted from bibliometric analysis techniques. In addition, a synthetic knowledge synthesis approach was used. A total of 234 publications were published in 107 sources in 2002-2023. The publications had 8797 citations, an average of 88 citations per publication. In terms of total link strength (TLS), links, a number of articles and citations, the US led all other countries in the field. Regarding authors, Hwang was the most frequently cited authors (n = 348). According to trend topics analysis, the keywords "gamification", "simulation", "attitude", "clinical competence" and "online learning" have emerged in the field. Research on mobile learning in nursing education has been increasing in recent years. The findings of this study can provide new ideas in the applications of mobile learning in nursing education to researchers or nursing faculties in the field.


Differential pulse polarography of tetracycline: determination of complexing tendencies of tetracycline analogs in the presence of cations.
The complexation tendencies, stoichiometries, and stability constants for tetracycline, minocycline, and demeclocycline with the metallic ions calcium(II), magnesium (II), zinc(II), aluminum(III), iron(II), and iron (III) were evaluated using a polarographic technique. Changes in pulse peak heights for each tetracycline deravative were measured as a function of cation concentration. The method provides an in vitro method of evaluating the selectivity of particular metal ions for different tetracycline analogs.


Extraction of biodegradable microplastics from tissues of aquatic organisms.
Biodegradable plastics (BPs) have been given high hopes to substitute conventional plastics, but their biodegradation requires strict conditions. BPs can accumulate for a long time in the environment and even derive biodegradable microplastics (BMPs), thus threatening wildlife and ecosystems. However, no efficient method is available for extracting BMPs from organisms' tissues. This study used multi-criteria decision-making (MCDM) methods to comprehensively evaluate and optimize extraction protocols of five BMPs from economic aquatic species. Digestion time, digestion efficiency, mass loss, cost, polymer integrity and size change were selected as evaluating indictors. According to the screening results of MCDM methods, Pepsin+H2O2 was selected as the optimal digestion method of BMPs because of its highest comprehensive score, which has high digestion efficiency (99.56%) and minimum plastic damage. Compared with olive oil, NaI is more suitable for separating BMPs from the digested residues. Furthermore, the combination of Pepsin+H2O2 digestion and NaI density separation was used to extract all five kinds of BMPs from the bivalve, crab, squid, and crayfish tissues, and all the recovery rates exceeded 80%. These results suggest that the optimal protocol is practicable to extract various BMPs from various aquatic organisms.


Receipt of preventive medical care and medical screening for patients with mental illness: a comparative analysis.
There has been long-standing concern about the delivery of preventive and screening services to patients with mental illness. We aimed to examine whether the quality of preventive care received by patients with mental health conditions differs from that received by individuals who have no comparable mental disorder. Our hypothesis was that patients with mental illness would be in receipt of lower quality or lower frequency of preventive care. Studies that examined the quality of care in those with and without comorbid mental illness were reviewed and comparative data extracted. By using only comparative studies we hope to ascertain whether inequalities in care existed by virtue of psychiatric diagnoses (or closely affiliated factors). We identified 26 studies that examined preventive care in individuals with vs. without psychiatric illness. From these eligible studies, 61 comparisons were documented across 13 health care domains. These included mammography, cervical smears, vaccinations, cholesterol screening, lifestyle counseling, colonoscopy. Twenty-seven comparisons revealed inferior preventive health care in those with mental illness, but 10 suggested superior preventive health care and 24 reached inconclusive findings. Inferior preventive care was most apparent in those with schizophrenia and in relation to osteoporosis screening, blood pressure monitoring, vaccinations, mammography and cholesterol monitoring. We conclude there is strong evidence to suggest that the quality of preventive and screening services received by patients with mental illness is often lower, but occasionally superior to that received by individuals who have no comparable mental disorder. More work must be done to improve the quality of medical and preventive care for individuals with mental illness.


Derivation & validation of glycosylated haemoglobin (HbA 1c ) cut-off value as a diagnostic test for type 2 diabetes in south Indian population.
Glycosylated haemoglobin (HbA 1c ) has been in use for more than a decade, as a diagnostic test for type 2 diabetes. Validity of HbA 1c needs to be established in the ethnic population in which it is intended to be used. The objective of this study was to derive and validate a HbA 1c cut-off value for the diagnosis of type 2 diabetes in the ethnic population of Rayalaseema area of south India. In this cross-sectional study, consecutive patients suspected to have type 2 diabetes underwent fasting plasma glucose (FPG) and 2 h post-load plasma glucose (2 h-PG) measurements after a 75 g glucose load and HbA 1c estimation. They were classified as having diabetes as per the American Diabetes Association criteria [(FPG ≥7 mmol/l (≥126 mg/dl) and/or 2 h-PG ≥11.1 mmol/l (≥200 mg/dl)]. In the training data set (n = 342), optimum cut-off value of HbA 1c for defining type 2 diabetes was derived by receiver-operator characteristic (ROC) curve method using oral glucose tolerance test results as gold standard. This cut-off was validated in a validation data set (n = 341). On applying HbA 1c cut-off value of >6.3 per cent (45 mmol/mol) to the training data set,sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for diagnosing type 2 diabetes were calculated to be 90.6, 85.2, 80.8 and 93.0 per cent, respectively. When the same cut-off value was applied to the validation data set, sensitivity, specificity, PPV and NPV were 88.8 , 81.9, 74.0 and 92.7 per cent, respectively, although the latter were consistently smaller than the proportions for the training data set, the differences being not significant. HbA 1c >6.3 per cent (45 mmol/mol) appears to be the optimal cut-off value for the diagnosis of type 2 diabetes applicable to the ethnic population of Rayalaseema area of Andhra Pradesh state in south India.


Nix Nought Nothing: fairy tale or real deal.
Nix was first described in the heart as the protein product of a differentially expressed mRNA detected by hybridization to a partial cDNA sequence tag on an RNA expression array. Over the subsequent 8 years Nix has become the prototypical transcriptionally-regulated cardiac myocyte "suicide" gene and has been used as a model to interrogate mechanisms of programmed cardiomyocyte death in hypertrophy and heart failure. Nix stimulates conventional apoptosis mediated via the intrinsic mitochondrial pathway, but emerging evidence indicates that Nix also controls programmed necrosis dependent upon sarcoplasmic reticular-mitochondrial tethering, calcium cross-talk, and the mitochondrial permeability transition. Recent studies have also described Nix labeling of senescent cardiomyocyte mitochondria for autophagic elimination, elucidated a physiological mitochondrial quality control Nix function; so-called "mitochondrial pruning". This article is part of a special issue entitled "Key Signaling Molecules in Hypertrophy and Heart Failure."


Wrapping things up about virus RNA replication.
All single-stranded 'positive-sense' RNA viruses that infect mammalian, insect or plant cells rearrange internal cellular membranes to provide an environment facilitating virus replication. A striking feature of these unique membrane structures is the induction of 70-100 nm vesicles (either free within the cytoplasm, associated with other induced vesicles or bound within a surrounding membrane) harbouring the viral replication complex (RC). Although similar in appearance, the cellular composition of these vesicles appears to vary for different viruses, implying different organelle origins for the intracellular sites of viral RNA replication. Genetic analysis has revealed that induction of these membrane structures can be attributed to a particular viral gene product, usually a non-structural protein. This review will highlight our current knowledge of the formation and composition of virus RCs and describe some of the similarities and differences in RNA-membrane interactions observed between the virus families Flaviviridae and Picornaviridae.


Associative effects between Chlorella vulgaris microalgae and Moringa oleifera leaf silage used at different levels decreased in vitro ruminal greenhouse gas production and altered ruminal fermentation.
Moringa oleifera leaf silage and Chlorella vulgaris microalgae mixture used at different levels replacing concentrate feed mixture in the diets of ruminant were evaluated using an in vitro gas production technique. C. vulgaris was included in rations at 1, 2, and 3% concentrations. The concentrate feed mixture was replaced by M. oleifera silage up to 100%. Productions of total gas, methane (CH4), and carbon dioxide (CO2) and ruminal fermentation were measured. Interactions between M. oleifera and C. vulgaris levels were observed for the rate of total gas production, lag time of CH4 production, pH, and concentrations of ammonia-N (NH3-N), total volatile fatty acid (VFA), and propionate. The lower level of C. vulgaris increased total gas production and decreased CH4 and CO2 production as well as improved nutrient degradability compared to the other levels of C. vulgaris which showed less improvement in these parameters. The replacement levels of concentrate at 10 to 40% with M. oleifera linearly increased the asymptotic total gas production and degradabilities of dry matter and acid detergent fiber (P<0.05), while the replacement levels of 80 to 100% lowered the asymptotic (P<0.01) for the ration containing 1% C. vulgaris. Rations containing M. oleifera linearly increased the lag time of total gas production (P<0.05), neutral detergent fiber degradability, and ruminal bacteria count and decreased the asymptotic CH4 and CO2 production and ruminal protozoal count (P<0.05). For the rations containing 2 and 3% C. vulgaris, M. oleifera linearly (P<0.01) decreased the asymptotic total gas, CH4 and CO2 production, and ruminal protozoal count. The lag time of CH4 production was not affected at 1% C. vulgaris, but reduced linearly at 2% and 3% C. vulgaris. Ruminal pH was not affected by M. oleifera, but was increased by C. vulgaris at 3% level. Overall, M. oleifera in the ration containing C. vulgaris at all levels increased ruminal NH3-N concentration; however, C. vulgaris at 2% level and M. oleifera at levels up to 40% lowered NH3-N concentration. M. oleifera rations with 1% and 2% C. vulgaris increased the concentrations of total VFA and propionate, whereas these variables were not affected at 3% C. vulgaris level. In conclusion, replacement of concentrate mixture with M. oleifera at 30% level and C. vulgaris at 1% in the diet due to associative effects may improve ruminal fermentation and feed degradability while decreasing CH4 production.


Response of vaccination on community transmission of COVID-19: a dynamical approach.
Due to the severity of COVID-19, vaccination campaigns have been or are underway in most parts of the world. In the current circumstances, it is obligatory to examine the response of vaccination on transmission of the SARS-CoV-2 virus when there are many vaccines available. Considering the importance of vaccination, a dynamic model has been proposed to provide an insight in the same direction. A mathematical model has been developed where six population compartments viz. susceptible, infected, vaccinated, home-isolated, hospitalized and recovered population are considered. Moreover, two novel parameters are included in the model to ascertain the effectiveness and speed of the vaccination campaign. Reproduction number and local stability of both the disease-free and endemic equilibrium points are studied to examine the nature of population dynamics. Graphical results for the community stage of COVID-19 infection are simulated and compared with real data to ascertain the validity of our model. The data is then studied to understand the impact of vaccination. These numerical results evidently demonstrate that home isolation and hospitalization should continue for the infected people until the transmission of the virus from person to person reduces sufficiently after completely vaccinating every nation. This model also recommends that all type of prevention measures should still be taken to avoid any type of critical situation due to infection and also reduce the death rate.


Distribution of Marburg virus in Africa: An evolutionary approach.
The aim of this study was to investigate the origin and geographical dispersion of Marburg virus, the first member of the Filoviridae family to be discovered. Seventy-three complete genome sequences of Marburg virus isolated from animals and humans were retrieved from public databases and analysed using a Bayesian phylogeographical framework. The phylogenetic tree of the Marburg virus data set showed two significant evolutionary lineages: Ravn virus (RAVV) and Marburg virus (MARV). MARV divided into two main clades; clade A included isolates from Uganda (five from the European epidemic in 1967), Kenya (1980) and Angola (from the epidemic of 2004-2005); clade B included most of the isolates obtained during the 1999-2000 epidemic in the Democratic Republic of the Congo (DRC) and a group of Ugandan isolates obtained in 2007-2009. The estimated mean evolutionary rate of the whole genome was 3.3×10(-4) substitutions/site/year (credibility interval 2.0-4.8). The MARV strain had a mean root time of the most recent common ancestor of 177.9years ago (YA) (95% highest posterior density 87-284), thus indicating that it probably originated in the mid-XIX century, whereas the RAVV strain had a later origin dating back to a mean 33.8 YA. The most probable location of the MARV ancestor was Uganda (state posterior probability, spp=0.41), whereas that of the RAVV ancestor was Kenya (spp=0.71). There were significant migration rates from Uganda to the DRC (Bayes Factor, BF=42.0) and in the opposite direction (BF=5.7). Our data suggest that Uganda may have been the cradle of Marburg virus in Africa.


Transport of amino acids by the human placenta: predicted effects thereon of maternal hyperphenylalaninaemia.
Brush border and basal plasma membrane vesicles prepared from normal term human placental syncytiotrophoblast have been used to study amino acid transport. Such studies are reviewed and novel results presented which confirm that saturation of placental transport by phenylalanine is unlikely to limit delivery of this amino acid to the fetus even with grossly raised maternal concentrations. Such raised maternal levels of phenylalanine are, however, likely to severely embarrass the delivery to the fetus across the placental brush border membrane of L-tyrosine and, to a lesser extent, of L-tryptophan. Reasons for thinking that this may be relevant to the fetal damage found in maternal PKU are discussed.


Square-wave endurance exercise test (SWEET) for training and assessment in trained and untrained subjects. III. Effect on VO2 max and maximal ventilation.
The effect of training on VO2 max, endurance capacity (EC) and ventilation during maximal exercise (VE max) were studied in 17 normal subjects aged 21--51 years. At the beginning of the study 11 of the subjects (eight women and three men) were untrained (U) and six others (three women and three men) trained regulatory (T). A maximal intensity exercise (on a cycle ergometer) which could be sustained for 45 min (MIE45) was performed three times per week for 6 weeks; the total mechanical work (TMW) corresponding to the MIE45 per session varied between 3.14 and 9.24 kJ . kg-1. Before training, VO2 max (a), VEmax (b), and TMW (c) were higher in T than in U subjects. Training increased these variables in most of the subjects; the increase being significantly higher (mean +/- SEM) in U (a = +29.9 +/- 3.8%; b = 49.6 +/- 6.5%; c = 47 +/- 6.9%) than in T subjects (a = 6.6 +/- 3.8%; b = 17.5 +/- 3.6+; c = 19.1 +/- 2.8%). In all but three cases the % increase of TMW was higher than that of VO2 max, suggesting a higher sensitivity of TMW in measuring EC. The significant increase in VE max, maximal voluntary ventilation, peak flows (inspiratory and expiratory) and static maximum voluntary ventilation, peak flows (inspiratory and expiratory) and static maximum pressures indicate that this training protocol improves in healthy subjects the performance of respiratory muscles as well.


Human antiretinal antibodies in toxoplasma retinochoroiditis.
Toxoplasma retinochoroiditis (TR) is an important cause of blindness and visual morbidity, affecting young adults. It has been postulated that some of the retinal damage observed in TR is due to antiretinal autoimmune mechanisms. Humoral antiretinal autoimmunity in TR was investigated by indirect immunofluorescence (IIF) on normal human cadaveric retina and by a human retinal S-antigen ELISA. 36 patients with TR were separated on clinical grounds into those with first recurrence of disease (n = 18) or those with multiple recurrences (n = 18). Patients were also segregated into those with active (n = 28) or quiescent disease (n = 8). Serum from 16 normal controls (six with positive toxoplasma serology and 10 without) with no evidence of eye disease and 12 patients with idiopathic retinal vasculitis (IRV) were also tested. Sera from 34 of the 36 patients (94%) with TR demonstrated photoreceptor layer reactivity by IIF contrasting with six of 16 normal controls (p = < 0.001) and three of 12 IRV patients (p = < 0.001). Titres of antiphotoreceptor antibody were also higher among TR patients than controls. Sera from 27 of the 36 TR patients, 10 of 16 normals, and nine of 12 retinal vasculitis patients possessed anti-human retinal S-antigen antibodies at a titre of 1:400 or more as assessed by ELISA (p = > 0.05). Antiretinal autoantibody as detected by IIF did not run in parallel with S-antigen reactivity. The data indicate that the extent of antiretinal reactivity within TR is not accounted for by anti-S-antigen antibodies alone. This remarkably high prevalence of antiphotoreceptor antibody in TR as opposed to that found in either healthy or disease controls suggest that these antibodies may be co-pathogenic in toxoplasma retinochoroiditis.


The role of serotonin release and autoreceptors in the dorsalis raphe nucleus in the control of serotonin release in the cat caudate nucleus.
Using a push-pull cannula technique and an isotopic method for estimating [3H]serotonin continuously synthesized from [3H]tryptophan, the effects of changes in the release of serotonin in the dorsalis raphe nucleus on in vivo release of [3H]serotonin in the cat caudate nucleus were investigated. The increase in the release of serotonin in the dorsalis raphe nucleus caused by local application of parachlorophenylethylamine (10(-6) M) reduced striatal [3H]serotonin release. This inhibition in serotonin release in the striatum was blocked by the prior and continuous local superfusion of the dorsal raphe with methiothepin (10(-6) M), a serotonin autoreceptor antagonist. GABA (5 x 10(-5) M) applied to the dorsalis raphe reduced both local and striatal release of [3H]serotonin. However, picrotoxin (10(-5) M), a GABA A receptor antagonist applied locally in the dorsalis raphe nucleus increased [3H]serotonin release while decreasing striatal [3H]serotonin release. This decrease in serotonin release in the striatum was again blocked by continuous superfusion of the raphe with methiothepin. Furthermore, superfusion of serotonergic cell bodies of the dorsalis raphe nucleus with methiothepin alone never altered local release or striatal release of [3H]serotonin. These data strongly suggest that the release of serotonin from the cell body in the dorsalis raphe nucleus phasically controls release of the amine at the axonal nerve ending through serotonergic autoreceptors located on serotonergic nerve cell bodies in the dorsalis raphe nucleus. The origin of the serotonin released in the dorsalis raphe nucleus and the possibility that this type of regulation could be related to changes in nerve impulse conduction of the serotonergic raphe-striatal system are discussed.


Project management: a core competency for professional nurses and nurse managers.
Project management is a core competency for nurses and managers. In this article, the project life cycle and project planning and controlling tools are described. Managers can readily see that using project management can be done with minimal training and disruption to the organization. Clearly, the costs of adopting project management are small compared to the benefits in productivity, reduced work stress, and reduced interpersonal conflict.


Design of net-charged abc-type collagen heterotrimers.
Net-negatively-charged heterospecific A:B:C collagen peptide heterotrimers were designed using an automated computational approach. The design algorithm considers both target stability and the energy gap between the target states and misfolded competing states. Structural characterization indicates the net-negative charge balance on the new designs enhances the specificity of the target state at the expense of its stability.


Flow cytochemical patterns of white blood cells in human haematopoietic malignancies. I. Acute leukaemias.
Peripheral blood samples from 118 patients with acute leukaemia (68 untreated; 50 treated) were measured with the Technicon H-6000 automated haematology analyser. This instrument provides, in addition to measurements of the classical haematology parameters (i.e. cell counts, haemoglobin concentration, etc.), a differential count on 10(4) WBC effected by means of flow cytochemistry (peroxidase content) and volume (light scatter) discrimination. Disregarding RBC and platelet counts and their volume distribution profiles, the most important diagnostic parameters for leukaemic disease were the WBC count, the WBC differential count, and the proportions of large unstained cells (LUC) and high peroxidase (HPX) cells obtained by the automated differential count as well as the mean value of the WBC peroxidase content distribution (MPA). Granulocytic leukaemias had lower MPA than normal and lymphocytic leukaemias had MPA values above normal. M1 leukaemias were also characterized by large proportions of LUC and low fractions of HPX, while M2 leukaemias showed low LUC with high HPX. M3 leukaemias had low LUC and very high HPX. M4 leukaemias had large LUC and 'monocytic' components and a modest fraction of HPX. M5 leukaemias had very large numbers of LUC, 'monocytes' and 'lymphocytes' and a normal HPX. For M1 leukaemia, the presence of less than 7% LUC following induction treatment was related to morphological changes of normal cells induced by chemotherapy while LUC above 10% usually indicated unsuccessful induction associated with the presence of residual blasts. If treatment was successful, M2 and M3 leukaemias characteristically decreased their HPX population. All M4 leukaemias studied by us failed to enter remission and continued to display high proportions of HPX and LUC. Similarly, most M5 leukaemias had a poor response to treatment and always showed a very high proportion of LUC. Untreated lymphocytic leukaemias demonstrated high LUC, normal HPX and a high proportion of 'lymphocytes'. Hairy cell leukaemias showed almost equal proportions of 'lymphocytes' and LUC. Successful chemotherapy of all lymphoid leukaemia entities was associated with rapid decreases in LUC, slower decrements of 'lymphocytes' and moderate and transient increments in HPX. Thus, flow cytochemistry can assist not only in the segregation of acute leukaemias along with FAB classification with nonmorphologic criteria, but also in the follow up of patients with these diseases.


Brain Oxygen Extraction Is Differentially Altered by Alzheimer's and Vascular Diseases.
Alzheimer's disease and vascular cognitive impairment (VCI), as well as their concurrence, represent the most common types of cognitive dysfunction. Treatment strategies for these two conditions are quite different; however, there exists a considerable overlap in their clinical manifestations, and most biomarkers reveal similar abnormalities between these two conditions. To evaluate the potential of cerebral oxygen extraction fraction (OEF) as a biomarker for differential diagnosis of Alzheimer's disease and VCI. We hypothesized that in Alzheimer's disease OEF will be reduced (decreased oxygen consumption due to decreased neural activity), while in vascular diseases OEF will be elevated (increased oxygen extraction due to abnormally decreased blood flow). Prospective cross-sectional. Sixty-five subjects aged 52-89 years, including 33 mild cognitive impairment (MCI), 7 dementia, and 25 cognitively normal subjects. 3T T2 -relaxation-under-spin-tagging (TRUST) and fluid-attenuated inversion recovery imaging (FLAIR). OEF, consensus diagnoses of cognitive impairment, vascular risk factors (such as hypertension, hypercholesterolemia, diabetes, smoking, and obesity), cognitive assessments, and cerebrospinal fluid concentration of amyloid and tau were assessed. Multiple linear regression analyses of OEF with diagnostic category (normal, MCI, or dementia), vascular risks, cognitive performance, amyloid and tau pathology. When evaluating the entire group, OEF was found to be lower with more severe cognitive impairment (β = -2.70 ± 1.15, T = -2.34, P = 0.02), but was higher with greater vascular risk factors (β = 1.36 ± 0.55, T = 2.48, P = 0.02). Further investigation of the subgroup of participants with low vascular risks (N = 44) revealed that lower OEF was associated with worse cognitive performance (β = 0.04 ± 0.01, T = 3.27, P = 0.002) and greater amyloid burden (β = 92.12 ± 41.23, T = 2.23, P = 0.03). Among cognitively impaired individuals (N = 40), higher OEF was associated with greater vascular risk factors (β = 2.19 ± 0.71, T = 3.08, P = 0.004). These findings suggest that OEF is differentially affected by Alzheimer's disease and VCI pathology and may be useful in etiology-based diagnosis of cognitive impairment. 1 TECHNICAL EFFICACY: Stage 3 J. MAGN. RESON. IMAGING 2020;52:1829-1837.


Prenatal murine skeletogenesis partially recovers from absent skeletal muscle as development progresses.
Skeletal muscle contractions are critical for normal skeletal growth and morphogenesis but it is unclear how the detrimental effects of absent muscle on the bones and joints change over time. Joint shape and cavitation as well as rudiment length and mineralisation were assessed in multiple rudiments at two developmental stages [Theiler stage (TS)24 and TS27] in the splotch-delayed "muscle-less limb" mouse model and littermate controls. Chondrocyte morphology was quantified in 3D in the distal humerus at the same stages. As development progressed, the effects of absent muscle on all parameters except for cavitation become less severe. All major joints in muscle-less limbs were abnormally shaped at TS24, while, by TS27, most muscle-less limb joint shapes were normal or nearly normal. In contrast, any joints that were fused at TS24 did not cavitate by TS27. At TS24, chondrocytes in the distal humerus were significantly smaller in the muscle-less limbs than in controls, while by TS27, chondrocyte volume was similar between the two groups, offering a cell-level mechanism for the partial recovery in shape of muscle-less limbs. Mineralisation showed the most pronounced changes over gestation. At TS24, all muscle-less rudiments studied had less mineralisation than the controls, while at TS27, muscle-less limb rudiments had mineralisation extents equivalent to controls. In conclusion, the effects of muscle absence on prenatal murine skeletogenesis reduced in severity over gestation. Understanding how mammalian bones and joints continue to develop in an environment with abnormal fetal movements provides insights into conditions including hip dysplasia and arthrogryposis.


Effectiveness of local anaesthesia techniques in patients undergoing transrectal ultrasound-guided prostate biopsy: a prospective randomized study.
This study was designed to compare the effectiveness of intrarectal lidocaine gel versus periprostatic lidocaine injection during transrectal ultrasound (TRUS)-guided prostate biopsy. Ninety men undergoing transrectal prostate biopsy from July through December 2004 were randomized into three groups of 30 patients each. Before the biopsy, patients in Group 1 received 20 mL of 2% lidocaine gel intrarectally; patients in Group 2 received 5 mL (2.5 mL per side) of 2% lidocaine solution injected near the junction of the seminal vesicle with the base of the prostate (along the neurovascular bundles), and patients in Group 3 (control group) received 5 mL (2.5 mL per side) of normal saline injected along the neurovascular bundles. Pain level after the biopsy was assessed using a 10-point linear visual analog scale (VAS). Results were statistically compared by the Wilcoxon Rank Sum test. Patients in Group 2 had significantly lower VAS scores than those in Group 3 (3.6 +/- 2.1 vs 5.8 +/- 1.9, P < 0.0001), but those in Group 1 did not (5.5 +/- 2.7 vs 5.8 +/- 1.9, P = 0.67). Gross hematuria, rectal bleeding, and hemospermia occurred in 36 (40.0%), 6 (7%) and 5 (6%) patients. One patient had temporary vasovagal syncope. No patient reported febrile urinary tract infection or urinary retention. Periprostatic injection of local anaesthetic is a safe technique that significantly reduces pain during prostate biopsy, whereas intrarectal lidocaine injection did not reduce pain. This safe, simple technique should be applied in men undergoing TRUS-guided prostate biopsy to limit patient discomfort.


The Landau-Zener-Stückelberg-Majorana transition in the T2 ≪ T1 limit.
Landau-Zener-Stückelberg-Majorana (LZSM) transitions occur between quantum states when parameters in the system's Hamiltonian are varied continuously and rapidly. In magnetic resonance, losses in adiabatic rapid passage can be understood using the physics of LZSM transitions. Most treatments of LZSM transitions ignore the T2 dephasing of coherences, however. Motivated by ongoing work in magnetic resonance force microscopy, we employ the Bloch equations, coordinate transformation, and the Magnus expansion to derive expressions for the final magnetization following a rapid field sweep at fixed irradiation intensity that include T2 losses. Our derivation introduces an inversion-function, Fourier transform method for numerically evaluating highly oscillatory integrals. Expressions for the final magnetization are given for low and high irradiation intensity, valid in the T2≪T1 limit. Analytical results are compared to numerical simulations and nuclear magnetic resonance experiments. Our relatively straightforward calculation reproduces semiquantitatively the well known LZSM result in the T2→0 limit.


A review of fixed phagocytic and pinocytotic cells of decapod crustaceans, with remarks on hemocytes.
Clearance of foreign materials from the hemocoel of decapod crustaceans involves several distinct kinds of cells. Proteins, and possibly viruses below 30 nm diameter, are known to be removed by the branchial podocytes, which are specialized pinocytotic nephrocytes located in the gills. These cells, and podocytes of the antennal gland (excretory organ) which may also be of importance in clearance, are similar to podocytes of Bowman's capsule of the vertebrate kidney. Phagocytic clearance of particulate material (with possible exception of the small viruses) is accomplished by three kinds of cells, one free and the other two fixed to tissues facing hemal spaces. The hemocytes, free cells suspended in the hemolymph, are the most abundant and generalized of these phagocytic cells. Phagocytic reserve cells are applied to myofibers in the heart of penaeid and palaemonid shrimp, and probably the same as reserve cells found throughout the hemocoel of all decapods. They are minimally involved in clearance of injected carbon and carmine, but are not known to phagocytize naturally occurring particles such as bacteria or viruses. The fixed phagocytes are very important in the clearance of some substances. They are located on the exterior surfaces of arterioles in hemal spaces of the hepatopancreas. They are highly specialized cells designed to sequester large amounts of various types of particulate matter, not only through phagocytosis but by trapping and retaining vast numbers of particles within a net- or sievelike layer of granular material which surrounds the free surface of the fixed phagocyte. Derivation, morphology, development, and function of the above cell types are described and discussed.


Ubiquitin: its potential significance in murine AA amyloidogenesis.
Amyloid enhancing factor (AEF), which has recently been shown to have identity with ubiquitin (Ub), is believed to play a causative role in experimentally induced AA amyloidosis in mice. We have examined the profile of Ub in activated leukocytes and splenic reticulo-endothelial (RE) cells and its relationship with serum amyloid A protein (SAA) and AA amyloid deposits in an alveolar hydatid cyst (AHC)-infected mouse model of AA amyloidosis. Two monospecific antibodies, anti-ubiquitin (RABU) and anti-mouse AA amyloid, were used as immunological probes to localize Ub, SAA, and AA amyloid. In response to AHC infection, the dull and diffuse Ub immunoreactivity in normal mouse leukocytes and RE cells promptly changed to a discrete granular pattern suggesting an increase in the intracellular concentration of Ub and the formation of Ub-protein conjugates. This corresponded to an elevation in SAA levels, SAA uptake by RABU-positive phagocytic cells, co-localization of Ub-SAA immunoreactive splenocytes in the perifollicular areas, and deposition of Ub-bound AA amyloid in the splenic and hepatic tissues. These results suggest that Ub-loaded monocytoid cells may play an important role in the physiological processing of the sequestered SAA into AA amyloid. Aspects of AA amyloidogenesis are discussed in relation to other experimental models in which stress-induced Ub-protein conjugate formation and its transport to lysosomal vesicles have been studied.


(Re)defining mindful eating into mindful eating behaviour to advance scientific enquiry.
Mindful eating has exceeded two decades of scientific enquiry but defining mindful eating has proven to be quite challenging. The inability to clearly define mindful eating led to variations in the description in academic and clinical literature, different psychometric tools and the development of a field that is lacking the preciseness that is needed to advance mindful eating - and the associated interventions - onto a level that is simple to comprehend and implement in practice. Drawing from traditional and contemporary mindfulness and mindful eating literature, this manuscript will attempt to define and describe mindful eating in the context of eating behaviours. The review of the literature has resulted in challenging areas around the main principles that should be included in defining the term mindful eating, and highlights the distinction between mindfulness and mindful eating, as well as behaviour and decision making within the context of mindful eating. In a field that is lacking transparency and methodological rigour, mindful eating behaviour is detailed as a new beginning in conducting precise experimental research and evidence-based interventions for clinical and non-clinical use.


Improving biogas quality and methane yield via co-digestion of agricultural and urban biomass wastes.
Impact of co-digestion versus mono-digestion on biogas and CH4 yield for a set of five biomass materials (vegetable food waste, cow dung, pig manure, grass clippings, and chicken manure) was investigated considering 95 different biomass mixes of the five materials under thermophilic conditions in bench-scale batch experiments over a period of 65days. Average biogas and CH4 yields were significantly higher during co-digestion than during mono-digestion of the same materials. This improvement was most significant for co-digestion experiments involving three biomass types, although it was independent of the specific biomasses being co-digested. Improvement in CH4 production was further more prominent early in the digestion process during co-digestion compared to mono-digestion. Co-digestion also appeared to increase the ultimate CH4/CO2 ratio of the gas produced compared to mono-digestion although this tendency was relatively weak and not statistically significant.


Estimation of Age by Evaluating the Occlusal Tooth Wear in Molars: A Study on Dakshina Kannada Population.
Assessment of teeth to estimate age in the living as well as the dead is well documented in the literature. Though applied in conjunction with other parameters in Gustafson's technique, attrition of teeth solely is an underexplored indicator for age estimation mainly in India. Most of the studies using attrition of teeth have been conducted in bioarchaeology, and in populations where studies are being conducted in forensic contexts, the results are debatable. Thus, the present study aimed to evaluate the accuracy of age estimation using the Average Stage of Attrition (ASA) method by Li and Ji in adults of the Dakshina Kannada region. This cross-sectional study assessed the degree of attrition in both maxillary and mandibular first and second molars of 136 adults of Dakshina Kannada origin (age range: 20-70 years) according to the 10 stages given by Li and Ji to derive population-specific linear regression equations. Univariate analysis of prediction of age with attrition showed a significant association of attrition score with age, stratified by sex, arch as well as in total (p-value <0.001) with a standard error of estimate of 9.231 years. The estimated age was within ±5 years of the actual age in 44.2% of the females and 50.0% of the males. A comparative review of 23 studies done to estimate age from attrition score clinically is documented in the manuscript. The findings of this study suggest that evaluation of tooth wear by the Average Stage of Attrition (ASA) method can be used as a non-invasive means to aid in the determination of age in adults of Dakshina Kannada origin. Although the error increases with age, this method provides a measurable means of seriation into older and younger categories.


Biochemical studied on Egyptian buffalo meat. Part 2. Determination of iron, zinc and copper.
A total of 128 samples of Egyptian buffalo meat were collected from animals differing in age, sex, season and cuts. Their samples were analysed for iron, zinc and copper contents. Statistical analysis of the data obtained shows, that zinc and copper differ significantly at 0.01 level in relation to cut variation. In case of female, they differ also at the same level in relation to season. Zinc differes significantly at 0.01 level seasonally and in male in relation to season. On the other hand copper differs significantly at 0.05 level for green season in relation to sex. Iron and copper show significant differences at 0.1 level due to sex and in dry season in relation to sex, respectively.


Selective induction of apoptosis in mouse and human lung epithelial cell lines by the tert-butyl hydroxylated metabolite of butylated hydroxytoluene: a proposed role in tumor promotion.
Butylated hydroxytoluene (BHT) causes lung injury in mice and promotes tumor formation. Hydroxylation of a tert-butyl group on BHT to yield the metabolite, 6-tert-butyl-2-[2'-(2'-hydroxymethyl)-propyl]-4-methylphenol (BHTOH), may be required. BHTOH is more potent than BHT on an equimolar basis in causing lung damage, enhancing lung tumor development, killing isolated bronchiolar non-ciliated Clara cells, and inhibiting lung epithelial gap junctional intercellular communication. One mechanism proposed for tumor promoting agents is selective cytotoxicity; killing normal cells allows uninhibited clonal expansion of neighboring initiated cells. We compared the abilities of BHT, BHTOH, and other BHT metabolites to kill non-tumorigenic and tumorigenic mouse and human lung cell lines, and examined the contribution of apoptosis to this cytotoxicity. These cells lack the cytochrome P450 2B isozyme necessary for converting BHT to BHTOH. BHTOH and 4-hydroperoxy-4-methyl-2,6-di-tert-butyl-2,5-cyclohex-adienone+ ++ (BHTOOH) were most toxic, BHT and 2,6-di-tert-butyl-1,4-benzoquinone (BHTQu) were less potent, and 4-methyl BHT metabolites that are not pneumotoxic were ineffective. BHTOH most strongly induced apoptosis, based on nuclear condensation and transmission electron microscopy. Non-tumorigenic cells were as susceptible to cell death as the neoplastic cell lines when apoptosis and necrosis are not distinguished, but more sensitive to BHTOH-induced apoptosis. An apoptotic mechanism may underlie the lung tumor promoting actions of BHTOH.


Syntheses and NMR characterizations of epimeric 4-deoxy-4-fluoro carbohydrates.
The synthesis and NMR characterizations of 1,2,3,6-tetra-O-benzoyl-4-deoxy-4-fluoro-β-d-galactopyranoside, the 4-deoxy-4-fluoro epimer of an intermediate in the synthesis of a drug substance, needed for use as a potential impurity standard and to confirm the stereoselectivity of a key fluorination step, are described.


The range of motor activation in the normal human cortex using bold FMRI.
Understanding and documenting the nature of normal human brain functional motor activation using functional Magnetic Resonance Imaging (fMRI) is necessary, if valid statements are to be made about normal and disease functional states using fMRI activation maps. The present study examines activation maps in "normal" adults. Six healthy adult volunteers performed three motor tasks isolating the tongue, non-dominant foot, and non-dominant thumb during a single magnetic resonance imaging (MRI)/(fMRI) scanning session. Group maps demonstrated discrete areas of activation that were task dependent. The degree of variability between the anatomical central location of global maximum intensity for each individual may mean extra care should be applied when using the global maximum to define the area of activation. These differences may represent anatomical variability among individuals, task complexity, paradigm design, data analysis techniques or a combination thereof, which form the basis of our ongoing research endeavors. Standard notions of strongly associated functions as related to anatomic foci may need to be revised.


Predictability of spontaneous thoracic curve correction after anterior thoracolumbar correction and fusion in adolescent idiopathic scoliosis. A retrospective study on a consecutive series of 29 patients with a minimum follow-up of 2 years.
According to the Lenke classification, a Type 5 adolescent idiopathic scoliosis can be surgically treated with selective anterior thoracolumbar or lumbar fusion. This study aims to predict the spontaneous correction of the unfused thoracic curve after anterior thoracolumbar fusion and to study whether age is of influence on this predictability. Retrospective study on a consecutive series of patients. Of a consecutive series of 38 patients with idiopathic thoracolumbar scoliosis, Lenke type 5, 29 patients were included in the study. All patients were treated with anterior spinal fusion and instrumentation. A minimum follow-up of 2 years was available for all patients (mean, 4 years; range, 2-17 years). To investigate the influence of age on the outcome, we divided the group into two subgroups: an adolescent (n=13) and an adult age group (n=16). The mean age in the adolescent group was 17 (range, 13-21 years) and 38 years (range, 22-54 years) in the adult group. Physiological measures include coronal Cobb angle, apical vertebral translation (AVT) and apical vertebral rotation (AVR), shoulder tilt, trunk shift, L4 tilt, and pelvic tilt. Relative corrections were computed for the thoracolumbar and thoracic curves in each patient using the following formula: (preoperative curve-postoperative curve)/preoperative curve×100 (%). The correlation coefficient between the relative (%) corrections of the thoracic and thoracolumbar curves was calculated for the whole group as for the two age subgroups. For radiographic evaluation, we used standing anteroposterior and lateral projections of the thoracolumbar spine to determine Cobb angle, AVT and AVR, and coronal balance. Both the thoracolumbar and thoracic curves in the whole group improved after surgery (45% and 19%, respectively, p<.01). In the adolescent age group, a significant correlation between the relative (%) correction of the thoracolumbar curve and the relative (%) correction of the thoracic curve was found (R=0.704; p=.01) and between age and relative (%) correction of the thoracic curve (R=-0.805; p<.01). These results show that the spontaneous correction of the thoracic curve is a reflection of the thoracolumbar curve correction in adolescent thoracolumbar idiopathic scoliosis. Moreover, the predictability of the thoracic curve correction in the individual patient seems to decrease with increasing age of the patient.


Effective wound closure with a new two-component wound closure device (Prineo™) in excisional body-contouring surgery: experience in over 200 procedures.
In excisional body-contouring surgery the surgeon is often confronted with time-consuming closure of long wounds. Recently, a new combination of a self-adhering mesh together with a liquid 2-octyl cyanoacrylate adhesive (Prineo™; Ethicon, Inc., Somerville, NJ, USA) has been introduced to replace intracutaneous running suture. An observational study was undertaken to evaluate the efficacy of the new wound closure device in excisional body-contouring procedures between January 2008 and November 2010. Wound characteristics were recorded in a prospectively maintained database. During the study period, 224 procedures in 180 patients were undertaken. Twenty-seven patients had two subsequent operations and four patients had three subsequent operations. Application of the new device was easy and safe and patient satisfaction with the results was generally high. However, intense local allergic reactions were seen in 4 patients (1.8%), which necessitated early removal and topical corticosteroid treatment. Prineo™ enables the surgeon to perform a quick and smooth skin closure, especially in long incisions frequently encountered in excisional body-contouring surgery. The application is fast and easy if basic guidelines are respected. Operating time is saved by eliminating the need for time-consuming intracutaneous running sutures. Removal is easy and painless for the patient. However, there is a potential for local allergic adverse effects of which the surgeon must be aware.


Hepatic triglyceride lipase in diabetic dogs.
Circulating triglyceride is cleared by a combination of hepatic triglyceride lipase (H-TGL) and lipoprotein lipase (LPL). Although LPL has been extensively studied in diabetes, the effect of insulinization on H-TGL activity has not been well characterized. To determine whether H-TGL activity is altered in insulin-deficient diabetes, postheparin plasma was obtained from eight beagle dogs: three normal (nondiabetic) control dogs and five pancreatectomized diabetic dogs were studied acutely in poor diabetic control (underinsulinized), and again in short-term good control (well insulinized). Plasma glucose, measured at the start of the studies, was 88 +/- 10 mg/100 mL (mean +/- SD) in the normal control dogs, 434 +/- 31 mL in pancreatectomized dogs in poor diabetic control, and 87 +/- 16 in good diabetic control. Peak (five minutes) postheparin plasma H-TGL activity was increased in dogs in poor diabetic control (212 +/- 43 nmol FFA/min/mL) v the normal control dogs (135 +/- 21 nmol FFA/min/mL, P less than 0.02). When the dogs were in good diabetic control, the peak H-TGL (202 +/- 40 nmol FFA/min/mL) was also significantly increased compared with the level in normal dogs, while the sum of five and 45 minute postheparin H-TGL levels for the dogs in good diabetic control was less than when they were in poor diabetic control (P less than 0.01). Thus, insulin-deficient diabetes in dogs increases H-TGL, and short-term improvement of glycemic control with insulin partially corrects this increase.


Proteins of bovine leudemia virus: p. 15 is the major phosphorprotein.
Sodium dodecylsulfate-polyacrylamide gel electrophoresis of bovine leukemia virus (BLV) grown in fetal lamb kidney cells in the presence of 32P-phosphoric acid showed that the slightly basic 15000 D protein (pp 15) is the major phosphorylated component of the virus. This result further distinguishes BLV from mammalian type C viruses which possess acidic major phosphorproteins.


Stability of enzyme inhibitors and lectins in foods and the influence of specific binding interactions.
Proteins with actual or potential antinutrient or toxicant activity found in foodstuffs include (1) enzyme inhibitors, especially those specific for serine proteinases and alpha-amylases, and (2) lectins (hemagglutinins). These inhibitors and lectins must be inactivated during processing or food preparation, usually by heat, to avoid possible undesirable effects. Knowledge of their heat stabilities thus helps determine conditions required for their inactivation or denaturation. Many are heat-stable proteins, and their conformations can be stabilized or destabilized by interactions with other constituents present in the food or the digestive tract. Differential scanning calorimetric (DSC) results show that specific binding interactions can lead to substantial increases in kinetic thermal stability of proteins. Examples of such stabilization include serine proteinase-proteinase inhibitor, alpha-amylase-amylase inhibitor, and metal ion-lectin complexes. The extent of thermal stabilization of proteinases in complexes with inhibitors is correlated with the equilibrium association constant. Presence of more than one denaturing unit revealed by DSC in complexes involving multiheaded inhibitors can be interpreted in relation to domain structures of the inhibitors. Basic information on stability of the enzyme inhibitors and lectins is relevant to food processing, quality, and safety.