Degradation of apolipoprotein B-100 in human chylomicrons.
The purpose of this study was to investigate the molecular forms of apolipoprotein B (ApoB) in human chylomicrons under well-preserved conditions. To this end, plasma and serum were collected from the same normal subjects after ingestion of a fatty meal. The samples were divided into three or four aliquots before the addition of various preservative mixtures, including antibiotics, antioxidants and proteinase inhibitors. The chylomicrons were isolated immediately, and all steps were carried out at or below 4 degrees C. Changes in the molecular weight of ApoB in chylomicrons were followed by a time study using 3.3% polyacrylamide gel electrophoresis containing SDS. ApoB from chylomicrons analyzed within 5 h of blood collection showed a single band with mobility identical to that of ApoB (ApoB-100) in low-density lipoproteins. When analyzed after 1-2 days, satellite bands smaller than ApoB-100 were observed, and a very faint band with Mr 200,000 appeared, which comigrated with intestinal ApoB (ApoB-48). Upon storage, the molecular weight of ApoB was smaller in chylomicrons subjected to a higher number of reflotations than those in chylomicrons washed less frequently, suggesting that purified chylomicrons degrade faster. A longer storage time at 4 degrees C (i.e., 7 or 14 days) revealed a stepwise degradation of ApoB, yielding Mr 200,000 band as the prominent form. The degradation of ApoB-100 was slower when both proteinase inhibitors, leupeptin and epsilon-amino caproic acid, were employed, and the appearance of Mr 200,000 band was quicker when the chylomicrons were processed at higher temperature (15-25 degrees C) in the absence of a proteinase inhibitor. Immunoblotting shows that the segment removed from ApoB-100 was the carboxyl-terminal portion. These results suggest the possible presence of a proteinase(s), which copurified with chylomicrons, and which converts ApoB-100 from a large to a smaller molecular form. Although the stop codon has been discovered recently in intestinal ApoB mRNA, which explains the mechanism for direct synthesis of ApoB-48, apparently ApoB-100 is also synthesized in the intestine of all eight subjects studied here, and the ApoB-100 degrades to a form which is ApoB-48-like.


Intradimeric Walker A ATPases: Conserved Features of A Functionally Diverse Family.
Nucleoside-triphosphate hydrolases (NTPases) are a diverse, but essential group of enzymes found in all living organisms. NTPases that have a G-X-X-X-X-G-K-[S/T] consensus sequence (where X is any amino acid), known as the Walker A or P-loop motif, constitute a superfamily of P-loop NTPases. A subset of ATPases within this superfamily contains a modified Walker A motif, X-K-G-G-X-G-K-[S/T], wherein the first invariant lysine residue is essential to stimulate nucleotide hydrolysis. Although the proteins in this subset have vastly differing functions, ranging from electron transport during nitrogen fixation to targeting of integral membrane proteins to their correct membranes, they have evolved from a shared ancestor and have thus retained common structural features that affect their functions. These commonalities have only been disparately characterized in the context of their individual proteins systems, but have not been generally annotated as features that unite the members of this family. In this review, we report an analysis based on the sequences, structures, and functions of several members in this family that highlight their remarkable similarities. A principal feature of these proteins is their dependence on homodimerization. Since their functionalities are heavily influenced by changes that happen in conserved elements at the dimer interface, we refer to the members of this subclass as intradimeric Walker A ATPases.


Vitreous surgery for hemorrhagic and fibrous complications of age-related macular degeneration.
We applied vitreous surgical techniques in the treatment of hemorrhagic and fibrous complications of choroidal neovascular membranes by removing subretinal scars or hemorrhage, or both, in four patients. The surgical goals were achieved in all patients. Visual acuity improved in three patients. The major complication was recurrent detachment associated with large retinotomies.


The effect of humic acids on the reverse osmosis treatment of hazardous landfill leachate.
This study deals with the treatment of hazardous waste landfill leachate with the help of reverse osmosis. The landfill is located in an abandoned brown coal pit in northern Bohemia. The leachate contained 7.2 g/L of dissolved inorganic salts. Among other contaminants were heavy metals, arsenic, ammonia nitrogen and associated organic pollutants, especially chlorinated compounds. A mobile membrane unit (LAB M30) equipped with a spiral wound element (FILMTEC SW30-4040), with a membrane area equaling 7.4 m2 was used for the pilot plant experiments. All experiments were carried out in batch mode. 94% conversion of the input stream into the permeate was achieved by use of a two-stage arrangement. Removal efficiencies of the monitored contaminants in the feed ranged from 94% for ammonia nitrogen to 99% for the two-valent ions. Removal efficiency for total dissolved solids was 99.3% on average. Due to varying levels of humic acids in the leachate throughout the year, fouling experiments were performed to investigate the separation process under different conditions than those used in the pilot plant. Leachates containing different concentrations of added humic acids were separated using a thin film composite on a propylene membrane. The added humic acids were obtained from samples of contaminated oxihumolite.


Evidence of an increased risk of hearing loss in heterozygous carriers in a Wolfram syndrome family.
Wolfram syndrome (MIM 222300) is characterized by juvenile-onset diabetes mellitus and optic atrophy. Previous linkage analyses in the United States and UK families have indicated that the gene for Wolfram syndrome (WFS) is localized on the short arm of chromosome 4. We herein confirm the linkage of the WFS locus to D4S3023 on 4p with a two-point LOD score of 3.42 in a large Japanese family with Wolfram syndrome. Multipoint linkage analysis revealed the maximum LOD score of 4.82 between D4S3023 and D4S394. We also evaluated putative health risks in carriers by multiple logistic analysis with independent variables, age, gender, and numbers of affected haplotypes and with dependent variables, such as hearing loss, diabetes mellitus, polyuria, incontinence, psychological illness, and visual acuity. The results showed that the putative disease haplotype increased a risk of hearing loss (odds ratio =35.68, 95% confidence interval =4.12-308.95) and diabetes mellitus (odds ratio =7.57, 95% confidence interval =2.03-28.23) independently. This is the first report of an increased health risk of illness in carriers, other than for psychiatric disease.


Mechanisms of macrolide resistance in Ureaplasma urealyticum: a study on collection and clinical strains.
Ureaplasma urealyticum is considered as a species which is intrinsically sensitive to macrolides (MIC less than 1 microgram/ml). Nevertheless, some of the strains recently isolated in our laboratories showed moderate to high levels of resistance (MICs ranging from 2 micrograms/ml to 100 micrograms/ml). In particular, a strain (CT28) isolated from a patient with nongonococcal urethritis long treated with erythromycin revealed a MIC greater than 100 micrograms/ml for this antibiotic. In order to investigate the mechanisms of resistance, strain CT28 and ten clinical and laboratory U. urealyticum strains were compared for the sensitivity to six antibiotics including three macrolides. Moreover the amount of macrolide uptake and the specific antibiotic binding to ribosomes were studied. Strain CT28 was resistant to josamycin, erythromycin, roxithromycin, lincomycin and clindamycin but sensitive to minocycline. When compared to a sensitive strain, strain CT28 showed a six-fold reduction in intracellular macrolide influx and accumulation and a reduction in antibiotic binding to ribosomes. The mechanisms implicated in these differences may be important for macrolide resistance in U. urealyticum.


Screening for addiction in patients with chronic pain and "problematic" substance use: evaluation of a pilot assessment tool.
Assessing for the presence of addiction in the chronic pain patient receiving chronic opioid analgesia is a challenging clinical task. This paper presents a recently developed screening tool for addictive disease in chronic pain patients, and pilot efficacy data describing its ability to do so. In a small sample of patients (n = 52) referred from a multidisciplinary pain center for "problematic" medication use, responses to the screening questionnaire were compared between patients who met combined diagnostic criteria for a substance use disorder and those who did not, as assessed by a trained addiction medicine specialist. Responses of addicted patients significantly differed from those of nonaddicted patients on multiple screening items, with the two groups easily differentiated by total questionnaire score. Further, three key screening indicators were identified as excellent predictors for the presence of addictive disease in this sample of chronic pain patients.


MAC reduction after intrathecal coadministration of GABA(A) agonist and glutamate antagonist in rats.
It has been reported that intrathecal coadministration of a GABA(A) agonist and a glutamate antagonist induces synergistic antinociceptive effects in rats. We hypothesized that this synergistic antinociceptive effect might induce a synergistic reduction in the minimum alveolar anesthetic concentration (MAC). The MAC for sevoflurane was determined before and after intrathecal administration of muscimol (GABA(A) agonist, 0.1-10 microg), AP-5 (N-methyl-D-aspartate [NMDA] antagonist, 0.1-10 microg), and YM872 (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid [AMPA] antagonist, 0.1-10 microg) in rats. The effects of coadministration of muscimol and AP-5 or YM872 on MAC reduction were also tested. Intrathecal administration of muscimol at doses of 1 and 10 microg significantly reduced the MAC by 34.5% +/- 3.3% and 46.9% +/- 4.4%, respectively (P < 0.01). Intrathecal administration of AP-5 at a dose of 10 microg and YM872 at a dose of 10 microg significantly reduced the MAC by 25.8% +/- 2.4% and 31.4% +/- 6.3%, respectively (P < 0.01). No additional reductions in MAC values were observed when a GABA(A) agonist was combined with either an NMDA or an AMPA antagonist. Intrathecal coadministration of a GABA(A) agonist and an NMDA or AMPA antagonist, which has been reported to produce a synergistic antinociceptive effect, did not induce a synergistic reduction in the MAC. The antinociceptive effect may not be the predominant factor in the reduction of the MAC induced by these drugs.


Prognostic factors of developmental outcome in neonatal seizures in term infants.
The purpose of this study was to identify prognostic indicators of neurodevelopmental outcome in term infants who experienced clinical neonatal seizure. This is a retrospective, observational hospital-based study. Term infants who experienced clinical neonatal seizure between January 1999 and December 2009 were enrolled. Adverse outcomes were defined as death, cerebral palsy, global developmental delay, and/or epilepsy. The associations between adverse outcomes and 17 variables, including sex, mode of delivery, being small of gestational age, maternal illness, perinatal insults, meconium stained liquor, Apgar score at 1 and 5 minutes, seizure onset age, seizure type, etiology, electroencephalography (EEG) findings, antiepileptic drug efficacy, presence of metabolic acidosis, and cranial ultrasonographic findings, and presence of congenital heart disease were analyzed. Among the 232 enrolled infants, 125 had a normal outcome and 14 had mild functional disability (59.9%), and 55 (23.7%) survived with one or more neurodevelopmental impairments (7 with cerebral palsy, 48 with global developmental delay), and 38 (16.4%) died. Forty-seven (23.0%) of the 204 patients who survived after the first discharge had epilepsy. Ten variables were associated with adverse outcome on univariate analysis, but only four variables, i.e., including abnormal cranial ultrasonography findings, abnormal anterior cerebral artery resistance index, abnormal EEG findings, and presence of congenital heart disease were independent predictors on multivariate logistic regression analysis. In term infants with neonatal seizures, several risk factors related to adverse outcome were recognized. Physicians should pay more attention to these factors when handling patients with neonatal seizures.


Numerical simulations of patient-specific models with multiple plaques in human peripheral artery: a fluid-structure interaction analysis.
Atherosclerotic plaque in the femoral is the leading cause of peripheral artery disease (PAD), the worse consequence of which may lead to ulceration and gangrene of the feet. Numerical studies on fluid-structure interactions (FSI) of atherosclerotic femoral arteries enable quantitative analysis of biomechanical features in arteries. This study aims to investigate the hemodynamic performance and its interaction with femoral arterial wall based on the patient-specific model with multiple plaques (calcified and lipid plaques). Three types of models, calcification-only, lipid-only and calcification-lipid models, are established. Hyperelastic material coefficients of the human femoral arteries obtained from experimental studies are employed for all simulations. Oscillation of WSS is observed in the healthy downstream region in the lipid-only model. The pressure around the plaques in the two-plaque model is lower than that in the corresponding one-plaque models due to the reduction of blood flow domain, which consequently diminishes the loading forces on both plaques. Therefore, we found that stress acting on the plaques in the two-plaque model is lower than that in the corresponding one-plaque models. This finding implies that the lipid plaque, accompanied by the calcified plaque around, might reduce its risk of rupture due to the reduced the stress acting on it.


Blood natural killer activity is reduced in men with occupational stress and job insecurity working in a university.
To examine the immune response to job strain and insecurity of 88 men working in a university, divided according to age and type of employment. Anxiety, job strain, job insecurity and subjective symptoms were measured by questionnaires. Blood NK cytotoxic activity was determined by an in vitro method and lymphocyte subpopulations by flow-cytometry analysis. Employees (over 40 years old) in a library showed higher values of job strain, anxiety and subjective symptoms and lower blood NK activity than the controls. The young employees with temporary employment showed high job insecurity and reduced blood NK activity, while the young sanitary staff with temporary position showed normal immune response. NK cytotoxic activity of the recruited men was negatively correlated with anxiety, work load and job insecurity. Not only anxiety and depression but also high levels of job strain and/or insecurity may affect the health status by reducing blood NK activity.


Striatal dopamine release in the rat during a cued lever-press task for food reward and the development of changes over time measured using high-speed voltammetry.
Substantia nigra dopamine neuronal activity in the primate is thought to be related to the error in predicting reward delivery. Dopamine release in rat nucleus accumbens has been shown to increase in relation to drug/food-seeking behaviour. It is not known how the release of dopamine in the striatum corresponds to the many distinct steps of a rewarded, cued task (e.g. recognizing the cue, executing the behaviour, anticipating the reward, receiving the reward) and how dopamine release then changes over time as task performance improves. To investigate dopamine release during a rewarded, cued task and the development of changes in dopamine release over time, changes in extracellular striatal dopamine concentration during a rewarded, cued lever-press task were measured a few days every week for 5 months using high-speed in vivo voltammetry. Rats were trained to press a lever after a tone to obtain a food reward. The reaction time for the lever press decreased gradually as training continued. Changes in dopamine concentration were measured in the anterior striatum (ventral portion) during the task performance after an initial 6-day familiarization period, in which the animals learned that a lever press yielded food, and a 5-week period for surgery, recovery, and electrode preparation. During the task performance, dopamine concentration started to increase just after the cue, peaked near the time of the lever press, and returned to basal levels 1-2 s after the lever press. This pattern of changes in dopamine concentration was observed over the 5 months of testing, the peak dopamine concentration increasing steadily until peaking at week 7, at which time the task performance had not yet improved significantly from week 2. By week 13, task performance had significantly improved and peak dopamine concentration had begun to subside. Thus, the increase in dopamine concentration after the cue was highest while the task was not yet perfected and subsided toward the end of the learning process. It was concluded that striatal dopamine release during a cued lever-press task is relevant to the novelty of the conditions.


Angioarchitecture and blood supply of micro- and macrometastases in human livers. An anatomic-pathological investigation using injection-techniques.
The histological and stereoscopical appearance of the metastatic vascular tree was examined in a series of 23 human metastatic livers using injection techniques. All metastases showed an abnormal 'construction-concept' of vascularization, never imitating the normal angioarchitecture of the liver parenchyma. 17 of 22 arterial injected livers contained hyper-, and 5 hypovascularized metastases. Two main types of hypervascularized metastases could be detected: a central type with blood supply via a main arterial 'hilus-like' branch, and a peripheral type with multiple arterial vessels infiltrating from the metastatic surrounding. Of 13 livers injected via the portal vein, 11 showed a portal supply of the metastases. Portal tumor thrombi were a frequent finding, possibly indicating a retrograde portal local tumor spread within the liver. No larger branches of the hepatic vein could be found in any metastases which were injected via the hepatic veins; all showed typical signs of compression, displacement and destruction. Micrometastases were found in the direct surroundings of almost half of all macrometastases. Up to a size of 100-200 microns they appeared to be mainly supplied by sinusoidal blood. With continuing growth, newly built capillaries could be shown in the direct surroundings of some of the micrometastases.


[On the use of corticosteroids for critically ill patients with SARS-CoV-2 interstitial pneumonia].
The health crisis caused by SARS-Cov2 continues to question the scientific community on an effective treatment to combat the disease. To do this, understanding the pathophysiology is a key element of the research. Although the use of corticosteroids is debated, recent publications on pathogenesis and histologic pattern allow us to consider their use on a different way. Through these two case reports, it seemed interesting to take stock of the most recent data in the literature and on the potential interest of the corticotherapy in specific critically ill patient's cases.


Synthesis of purine and pyrimidine bases and nucleosides under the cold plasma conditions (IX).
Living-matter precursors are obtained by the action of the high-frequency electrical discharges on a methane-ammonia-water mixture. Some purine and pyrimidine bases as well as nucleosides are detected and estimated quantitatively by column chromatography, one- and two-dimensional paper chromatography, paper chromatography with standard addition, colour tests as well as by optical density measurement within the UV region.


Self-enucleation of the right eye by a 38-year-old woman diagnosed with schizoaffective disorder: a case report.
Autoenucleation is a rare form of self-mutilation typically associated with psychiatric disorders such as schizophrenia, substance-induced psychosis and bipolar disorder. The act is usually unilateral, although bilateral attempts are also well documented in the literature. It is a case study involving a female patient (NN) diagnosed with schizoaffective disorder who self-enucleated her right eye following sexual intercourse with a fellow patient, and was forcefully prevented by staff from enucleating the second eye. We report recurrent episodes of her illness culminating in this severe act of self-mutilation. The motivational reasons behind this form of self-harm along with differential diagnosis and potential treatment options are discussed in the context of the available literature. Autoenucleation is commonly associated with religious and sexual delusions, and patients are thought to be at a greater risk of further self-harm. Timely antipsychotic treatment is likely to reduce the risk of such extreme forms of self-harm, although they can occur despite robust therapeutic intervention and treatment attempts. While self-inflicted eye injuries are rare, their prevention in what is typically a difficult patient group is fraught with challenges.


Lessons from multidisciplinary translational trials on anti-angiogenic therapy of cancer.
The importance of multidisciplinary translational clinical trials is obvious; however, making them work is complex and challenging. Here I present an argument for designing and implementing multidisciplinary mechanistic trials and present the lessons our team at the Massachusetts General Hospital Cancer Center has learned from two such trials in cancer patients with locally advanced rectal carcinomas and recurrent glioblastomas.


Prenatal stress reduces estradiol-induced prolactin release in male and female rats.
Prenatal stress is a potent disruptor of the normal course of sexual differentiation, affecting both males and females. In the present study, we wished to examine a sexually dimorphic endocrine response, estradiol (E2)-induced prolactin (Prl) release, in prenatally-stressed (P-S) males and females. Sprague-Dawley female rats were timed-mated (+ sperm = Day 1). From gestation days 15-22 one group of females was subjected to a thrice-daily regimen of heat and restraint stress (0830, 1230, and 1630 hr) consisting of placing the rats into a Plexiglas restraint tube over which were poised two 100 W floodlights. Control females remained undisturbed throughout pregnancy. At parturition all offspring were cross-fostered to untreated, recently-parturient dams and weaned at 25 days of age. Separate groups of P-S and Control males and females were gonadectomized and, for males, paired testes weights and body weights were recorded. Four days later the animals were implanted with Silastic capsules containing E2, and fitted with intra-atrial cannulae. The following day, blood samples were taken at 0900, 1300, 1500, and 1700 hr for a total of five days. Beginning with the 1700 hr sample on Day 2, and with the exception of the 1500 hr sample on Day 3, P-S males had significantly lower plasma Prl values than Control males through Day 4, and at the 1500 hr sample on Day 5. Moreover, at no point did P-S males exhibit a significant daily afternoon increase in Prl values, whereas Control males did so on Days 2 and 4.(ABSTRACT TRUNCATED AT 250 WORDS)


Immunology of corneal allograft rejection. Associated human leucocyte populations.
Human serum samples and peripheral blood mononuclear leucocytes (PBML) were collected from ten corneal transplant recipients over a two-year period at intervals before and after surgery, and during and after episodes of immunologic (rejection) reaction. Serum was monitored for the development of antibodies to histocompatibility antigens and PBML were stained with a panel of monoclonal reagents specific for T cell and for monocyte populations using indirect immunofluorescence. Patients who demonstrated an elevation in the Leu 2a+ (suppressor/cytotoxic) T cell population following an immunologic reaction ultimately accepted their grafts, whereas patients whose Leu 2a+ population was unaffected developed irreversible graft clouding. Additionally, a direct positive correlation between the development of elevated levels of lymphocytotoxic antibodies and helper T cells was noted in some patients during immunologic reactions. Neither DR-positive nor monocyte population changes demonstrated any consistent correlation with rejection episodes or final graft outcome.


A highly sensitive electrochemical biosensor based on zinc oxide nanotetrapods for L-lactic acid detection.
An amperometric biosensor based on zinc oxide (ZnO) nanotetrapods was designed to detect L-lactic acid. The lactate oxidase was immobilized on the surface of ZnO nanotetrapods by electrostatic adsorption. Unlike traditional detectors, the special four-leg individual ZnO nanostructure, as an adsorption layer, provides multiterminal charge transfer channels. Furthermore, a large amount of ZnO tetrapods are randomly stacked to form a three-dimensional network naturally that facilitates the exchange of electrons and ions in the phosphate buffer solution. Utilizing amperometric response measurements, the prepared ZnO nanotetrapod L-lactic acid biosensor displayed a detection limit of 1.2 μM, a low apparent Michaelis-Menten constant of 0.58 mM, a high sensitivity of 28.0 μA cm(-2) mM(-1) and a good linear relationship in the range of 3.6 μM-0.6 mM for the L-lactic acid detection. This study shows that the biosensor based on ZnO tetrapod nanostructures is highly sensitive and able to respond rapidly in detecting lactic acid.


Locked-in-like fulminant infantile Guillain-Barré syndrome associated with herpes simplex virus 1 infection.
Guillain-Barré syndrome (GBS) may rarely manifest as a peripheral locked-in syndrome. Clinical and instrumental features of a fulminant form of infantile GBS were assessed. After 2 days of rhinitis, a 6-month-old infant was intubated in the emergency room for sudden-onset respiratory failure. Neurological examination showed generalized areflexic flaccid paralysis with no detectable interaction, which resembled a coma. Brain MRI was normal. Lumbar puncture showed pleocytosis (43 cells/mm(3)) and herpes simplex virus 1 (HSV1) PCR positivity. EEG showed normal sleep-wake cycles, and EMG demonstrated nerve inexcitability. Acyclovir and immunoglobulins provided no benefit. After 1 week, lumbar puncture showed albuminocytological dissociation (protein 217 mg/dl). Plasmapheresis was then started, and progressive improvement occurred. At age 1 year, the child had recovered well with residual distal lower limb hyporeflexic weakness. A fulminant infantile GBS variant presenting as peripheral locked-in syndrome can be associated with HSV1 infection likely due to autoimmune cross-reactivity.


DNA Methylation Abnormalities and Altered Whole Transcriptome Profiles after Switching from Combustible Tobacco Smoking to Heated Tobacco Products.
The use of heated tobacco products (HTP) has increased exponentially in Japan since 2016; however, their effects on health remain a major concern. Tsuruoka Metabolome Cohort Study participants (n = 11,002) were grouped on the basis of their smoking habits as never smokers (NS), past smokers (PS), combustible tobacco smokers (CS), and HTP users for <2 years. Peripheral blood mononuclear cells were collected from 52 participants per group matched to HTP users using propensity scores, and DNA and RNA were purified from the samples. DNA methylation (DNAm) analysis of the 17 smoking-associated DNAm biomarker genes (such as AHRR, F2RL3, LRRN3, and GPR15), as well as whole transcriptome analysis, was performed. Ten of the 17 genes were significantly hypomethylated in CS and HTP users compared with NS, among which AHRR, F2RL3, and RARA showed intermediate characteristics between CS and NS; nonetheless, AHRR expression was significantly higher in CS than in the other three groups. Conversely, LRRN3 and GPR15 were more hypomethylated in HTP users than in NS, and GPR15 expression was markedly upregulated in all the groups when compared with that in NS. HTP users (switched from CS <2 years) display abnormal DNAm and transcriptome profiles, albeit to a lesser extent than the CS. However, because the molecular genetic effects of long-term HTP use are still unknown, long-term molecular epidemiologic studies are needed. This study provides new insights into the molecular genetic effects on DNAm and transcriptome profiles in HTP users who switched from CS.


Physicochemical properties of sorghum flour are selectively modified by combined germination-fermentation.
The combined effects of grain germination and of subsequent fermentation on the physicochemical properties of sorghum flour were investigated by studying the structural changes occurring in the starch and protein fractions and by assessing their effects on physical properties of the resulting materials most relevant to end use. The sequential treatments were more effective than either individual treatment in the modification of starch-related properties, whereas modification of the protein components only occurs in the fermentation step, almost regardless of a previous germination step. The resulting profile of physicochemical traits offers several hints as for the suitability of flour from treated sorghum as an ingredient for various types of gluten-free food products, and provides a basis for expanding the use of processed sorghum in applications other than traditional African foods.


The influence of exercise on postprandial triacylglycerol metabolism.
Trained people exhibit low plasma concentrations of triacylglcyeride (TAG) in both fasted and postprandial states. This mainly reflects enhanced uptake of TAG into skeletal muscle, via enhanced activity of lipoprotein lipase, the rate-limiting step in TAG removal. Endurance athletes possess a large, well-vascularised muscle mass and this may contribute through the increased availability of endothelial binding sites for LPL. However, each session of exercise stimulates a delayed increase in LPL activity so that prior exercise enhances uptake into muscle. Intramuscular TAG is one source of energy for muscular contraction so this may serve to replenish muscle nutrient stores which have been diminished by exercise. Regular, frequent aerobic exercise may oppose the atherogenic disturbances to lipoprotein metabolism evident during the postprandial period. It may also, by favouring the disposition of dietary fatty acids in muscle, improve the matching of fat oxidation to fat intake and hence help with maintenance of a desirable level of body fatness.


Paternal behavior in the Mongolian gerbil (Meriones unguiculatus): Estrogenic and androgenic regulation.
Here, we analyzed the effects of testosterone (T) and its metabolites, estradiol (E2) and dihydrotestosterone (DHT), on the onset of paternal behavior in virgin male Mongolian gerbils (Meriones unguiculatus). We hypothesized that T and E2, but not DHT, would facilitate the onset of paternal behavior. Seventy males displaying aggression toward pups were selected through a paternal behavior screening test. Forty males were bilaterally castrated. Of them, 10 were implanted with T, 10 with E2, and 10 with DHT, and 10 received no treatment. Another 30 males underwent a sham procedure. In these gerbils, T, E2 and DHT were measured to obtain the basal levels of these hormones. After treatment, the paternal behavior test was conducted again. Blood samples were obtained immediately after the administration of the test for the quantification of T, E2 and DHT by radioimmunoassay. Surprisingly, 100% of the males that received T, E2 and DHT implants stopped being aggressive and became paternal. Castrated and sham-operated males displayed no changes in their aggressive behaviors. This is the first report that T and its metabolites are involved in neuroendocrine mechanisms that inhibit aggression toward pups and facilitate paternal behavior in virgin male Mongolian gerbils. In addition, this is the first report of regulation of paternal behavior in a rodent by estrogenic and androgenic pathways.


The connectivity underlying the orientation selectivity in the infragranular layers of monkey striate cortex.
The striate cortex of the monkey was studied with an array of 30 closely spaced microelectrodes. Responses to oriented light bars were recorded simultaneously, and interneuronal connectivity was inferred from spike train correlations of pairs of neurones. Between cells with parallel preferred orientations, interactions were strong at short ranges but negative or only weakly positive at separations of 0.3-0.4 mm. At these distances, the stronger correlations were observed between orthogonally oriented cells. The finding does not explain the generation of orientation selectivity, but it is in agreement with a cooperative principle explaining the spatially regular arrangement of oriented cells.


Maternal allergy is associated with surface-bound IgE on cord blood basophils.
The cell type(s) mediating the maternal influence on allergic disease in children remain unclear. We set out to define the relationship between maternal allergy and frequencies of cord blood (CB) basophils, and plasmacytoid dendritic cells (pDCs); to characterize surface-bound IgE and FcεRI expressions on these cells; and to investigate the association between maternal and CB serum IgE levels with surface-bound IgE and FcεRI expressions. One hundred and three mother/infant dyads were recruited prenatally, and maternal allergic history was recorded. Maternal blood was collected prior to delivery, and CB was collected after birth. Flow cytometry was used to identify CB basophils and pDCs and to determine surface-bound IgE and FcεRI expressions. Frequencies of CB basophils and pDCs were low and not related to maternal history of allergy. Percentages of CB basophils with surface-bound IgE were significantly higher in infants of allergic mothers compared with infants of non-allergic mothers (median, 59.60% vs. 19.70%, p = 0.01). IgE on CB basophils correlated with CB IgE levels (r = 0.72, p < 0.0001), but not with maternal IgE levels (r = 0.26, p = 0.06). IgE on CB pDCs was low and not significantly associated with maternal or CB IgE levels. Similarly, FcεRI expression by CB basophils and pDCs was not significantly associated with maternal or CB IgE levels. Frequencies of CB basophils and pDCs are not influenced by maternal allergy. CB basophils and pDCs have surface-bound IgE and express FcεRI; however, only IgE on CB basophils appears influenced by maternal allergy.


Wastewater toxicity removal: Integrated chemical and effect-based monitoring of full-scale conventional activated sludge and membrane bioreactor plants.
The literature is currently lacking effect-based monitoring studies targeted at evaluating the performance of full-scale membrane bioreactor plants. In this research, a monitoring campaign was performed at a full-scale wastewater treatment facility with two parallel lines (traditional activated sludge and membrane bioreactor). Beside the standard parameters (COD, nitrogen, phosphorus, and metals), 6 polynuclear aromatic hydrocarbons, 29 insecticides, 2 herbicides, and 3 endocrine disrupting compounds were measured. A multi-tiered battery of bioassays complemented the investigation, targeting different toxic modes of action and employing various biological systems (uni/multicellular, prokaryotes/eukaryotes, trophic level occupation). A traffic light scoring approach was proposed to quickly visualize the impact of treatment on overall toxicity that occurred after the exposure to raw and concentrated wastewater. Analysis of the effluents of the CAS and MBR lines show very good performance of the two systems for removal of organic micropollutants and metals. The most noticeable differences between CAS and MBR occurred in the concentration of suspended solids; chemical analyses did not show major differences. On the other hand, bioassays demonstrated better performance for the MBR. Both treatment lines complied with the Italian law's "ecotoxicity standard for effluent discharge in surface water". Yet, residual biological activity was still detected, demonstrating the adequacy and sensitivity of the toxicological tools, which, by their inherent nature, allow the overall effects of complex mixtures to be taken into account.


Gastrointestinal manifestations of migraine: meeting the treatment challenges.
Nausea is a defining feature of episodic migraine. Migraine-associated nausea can cause patients to delay or avoid taking oral medication. In April 2011, a round table of headache specialists and a gastroenterologist was convened to explore unmet needs in the treatment of migraine vis-à-vis gastrointestinal signs and symptoms. This supplement summarizes the proceedings of that roundtable meeting.


Cognitive Enhancement for Elderly Facing Dementia with the Use of Cognitive Rehabilitation Therapy Techniques and Psychological Treatment. A Case Study.
Psychological therapies in order to provide cognitive enhancement have gained some momentum the last decades. The goal of this case study was to evaluate the effects of a cognitive enhancement training program on daily living activities, cognition, and depression in a demented elderly participant. A 6-month training program was proposed for the participant, whose overall evaluation results suggest significant deficits impairment but whose response rate to the proposed tasks of the treatment was interestingly high. However, additional research is needed to overall evaluate the efficacy of the proposed method to elderly adults.


ER-mitochondrial junctions can be bypassed by dominant mutations in the endosomal protein Vps13.
The endoplasmic reticulum-mitochondria encounter structure (ERMES) complex tethers the endoplasmic reticulum and the mitochondria. It is thought to facilitate interorganelle lipid exchange and influence mitochondrial dynamics and mitochondrial DNA maintenance. Despite this important role, ERMES is not found in metazoans. Here, we identified single amino acid substitutions in Vps13 (vacuolar protein sorting 13), a large universally conserved eukaryotic protein, which suppress all measured phenotypic consequences of ERMES deficiency. Combined loss of VPS13 and ERMES is lethal, indicating that Vps13 and ERMES function in redundant pathways. Vps13 dynamically localizes to vacuole-mitochondria and to vacuole-nucleus contact sites depending on growth conditions, suggesting that ERMES function can be bypassed by the activity of other contact sites, and that contact sites establish a growth condition-regulated organelle network.


No significant difference in risk of prolonged opioid use following outpatient versus inpatient total shoulder arthroplasty: A propensity matched analysis.
The purpose of this investigation was to compare rates of filled opioid prescriptions and prolonged opioid use in opioid naïve patients undergoing total shoulder arthroplasty (TSA) in inpatient versus outpatient settings. A retrospective cohort study was conducted using a national insurance claims database. Inpatient and outpatient cohorts were created by identifying continuously enrolled, opioid naïve TSA patients. A greedy nearest-neighbor algorithm was used to match baseline demographic characteristics between cohorts with a 1:1 inpatient to outpatient ratio to compare the primary outcomes of filled opioid prescriptions and prolonged opioid use following surgery between cohorts. A total of 11,703 opioid naïve patients (mean age 72.5 ± 8.5 years, 54.5% female, 87.6% inpatient) were included for analysis. After propensity score matching (n = 1447 inpatients; n = 1447 outpatients), outpatient TSA patients were significantly more likely to fill an opioid prescription in the perioperative window compared to inpatients (82.9% versus 71.5%, p < 0.001). No significant differences in prolonged opioid use were detected (5.74% inpatient versus 6.77% outpatient; p = 0.25). Outpatient TSA patients were more likely to fill opioid prescriptions compared to inpatient TSA patients. The quantity of opioids prescribed and rates of prolonged opioid use were similar between the cohorts. Therapeutic Level III.


The clinical, myopathological, and molecular characteristics of 26 Chinese patients with dysferlinopathy: a high proportion of misdiagnosis and novel variants.
Dysferlinopathy is an autosomal recessive muscular dystrophy caused by pathogenic variants in the dysferlin (DYSF) gene. This disease shows heterogeneous clinical phenotypes and genetic characteristics. We reviewed the clinical and pathological data as well as the molecular characteristics of 26 Chinese patients with dysferlinopathy screened by immunohistochemistry staining and pathogenic variants in DYSF genes. Among 26 patients with dysferlinopathy, 18 patients (69.2%) presented as Limb-girdle Muscular Dystrophy Type R2 (LGMD R2), 4 (15.4%) had a phenotype of Miyoshi myopathy (MM), and 4 (15.4%) presented as asymptomatic hyperCKemia. Fifteen patients (57.7%) were originally misdiagnosed as inflammatory myopathy or other diseases. Fifteen novel variants were identified among the 40 variant sites identified in this cohort. Dysferlinopathy is a clinically and genetically heterogeneous group of disorders with various phenotypes, a high proportion of novel variants, and a high rate of misdiagnosis before immunohistochemistry staining and genetic analysis.


Widespread hepatitis B virus genotype G (HBV-G) infection during the early years of the HIV epidemic in the Netherlands among men who have sex with men.
Hepatitis B virus (HBV) variants belong to different genotypes, A-J, whose worldwide distribution is linked with geography, probably because viral spread was associated with ancient human migrations. HBV genotype G (HBV-G) is an aberrant genotype with little sequence divergence, suggesting a recent origin. HBV-G is strongly associated with certain risk groups such as intravenous drug users (IDUs) and men who have sex with men (MSM), but hardly with geography. The origin and epidemiology of HBV-G remain unresolved, as is the disease association. To estimate the prevalence and possible time of introduction of HBV-G into the MSM community in Amsterdam, the Netherlands, we have retrospectively analysed 226 blood serum samples from HBsAg positive MSM enrolled in the Amsterdam Cohort Studies (ACS) on HIV infection and AIDS dating from 1984 to 1999 using genotype-specific PCR assays. Of the 226 HBsAg-positive samples, 149 were HBV DNA positive. Of those, 104 were positive for HBV genotype A (HBV-A) and five for HBV-G, and 40 showed a dual infection with both HBV-A and HBV-G. Being HIV-infected was significantly associated with a reduced HBV DNA viral load in blood, but not with the prevalence of HBV-G. Early virus already contained stop codons in the precore region and a 36 bp insertion in the core gene which are the characteristics of HBV-G. HBV-G was introduced before 1985 into the Amsterdam MSM community. Early isolates show very limited sequence variation, confirming a low evolutionary rate. HBV-G acquisition was independent of HIV infection, but being HIV-infected was significantly associated with a reduced HBV viral load in blood, indicating a beneficial effect of early HIV infection in controlling HBV replication.


APACHE III score is superior to King's College Hospital criteria, MELD score and APACHE II score to predict outcomes after liver transplantation for acute liver failure.
The Model for End-Stage Liver Disease score and King's College Hospital (KCH) criteria are accepted prognostic models acute liver failure (ALF), while the use of (APACHE) scores predict to outcomes of emergency liver transplantation is rare. The present study included 87 patients with ALF who underwent liver transplantation. We calculated (KCH) criteria, as well as MELD, APACHE II, and APACHE III scores at the listing date for comparison with 3-month outcomes. According to the Youden-Index, the best cut-off value for the APACHE II score was 8.5 with 100% sensitivity, 49% specificity, 24% positive predictive value (PPV), and 100% negative predictive value (NPV). Patients with <8.5 points had a significantly higher survival rate (P < .05). The proposed APACHE III cut-off was 80. The APACHE III score demonstrated the highest specificity and PPV (90% specificity, 50% PPV). The NPV was 92%. With a 90-point threshold the specificity increased to 98% with 75% PPV and 89% NPV. Only 1 of 4 patients with a score >90 survived transplantation (P = .001). MELD score and KCH criteria were not significant (P > .05). According to the Hosmer-Lemeshow test, only the APACHE III score adequately describe the data. The APACHE III score was superior to KCH criteria, MELD score, and APACHE II score to predict outcomes after transplantation for ALF. It is a valuable parameter for pretransplantation patient selection.


Phospholipid in the hexagonal II phase is immunogenic: evidence for immunorecognition of nonbilayer lipid phases in vivo.
Immunization of mice with phosphatidylethanolamine in the hexagonal II phase but not the bilayer phase resulted in the induction of anti-phospholipid antibodies. These antibodies, which were strongly reactive with phosphatidylethanolamine and crossreactive with cardiolipin, had functional lupus anticoagulant activity and were characteristic of autoantibodies common in patients with autoimmune disease. Recognition of the hexagonal II phase by the afferent limb of the immune system suggests that nonbilayer phospholipids can arise in the course of membrane remodeling and induce the autoantibodies of disease.


LC-MS/MS bioanalysis of plasma 1, 14-tetradecanedioic acid and 1, 16-hexadecanedioic acid as candidate biomarkers for organic anion-transporting polypeptide mediated drug-drug interactions.
A robust LC-MS/MS assay was developed to quantify endogenous 1, 14-tetradecanedioic acid (TDA) and 1, 16-hexadecanedioic acid (HDA) in human plasma as potential biomarkers for evaluating drug-drug interactions mediated by the hepatic drug transporters, organic anion-transporting polypeptides. This assay was validated using fit-for-purpose approach over standard curve range of 2.5-1000 nM for TDA and HDA using analyte-free charcoal-stripped human plasma as the surrogate matrix. Chromatographic separation condition was successfully optimized to separate TDA from an interference peak while maintaining both analytes in neutral forms to minimize carryover issue. The described assay is currently applied to a clinical study for evaluating TDA/HDA as potential substitute biomarkers for drug-drug interaction studies.


Blue rubber bleb nevus syndrome: report of a case.
A 21-year-old man had blue rubber bleb nevus syndrome: 1) hemangiomas of the skin all over the body; 2) hemangiomas of the digestive system; 3) iron-deficiency anemia. A giant mass of hemangiomas in the tranverse colon was resected surgically.


Notch-1 signaling activates NF-κB in human breast carcinoma MDA-MB-231 cells via PP2A-dependent AKT pathway.
Breast cancer has a high incidence in the world and is becoming a leading cause of death in female patients due to its high metastatic ability. High expression of Notch-1 and its ligand Jagged-1 correlates with poor prognosis in breast cancer. Our previous work has shown that Notch-1 signaling pathway upregulates NF-κB transcriptional activity and induces the adhesion, migration and invasion of human breast cancer cell line MDA-MB-231. However, the role of Notch-1 in NF-κB activation is still poorly understood. Here, we aim to understand the exact mechanism that Notch-1 regulates NF-κB activity. In MDA-MB-231 cells where Notch-1 is constitutively activated, the phosphorylation of p85 and AKT (Tyr308/Ser473) is upregulated, indicating PI3K/AKT pathway is activated. Notch-1 activation caused the increase of PP2A phosphorylation at Tyr307, indicating Notch-1 inhibits PP2A activity. NF-κB transcriptional activity was evaluated by dual-luciferase reporter assay, and the results showed that, while silencing of Notch-1, PP2A activity was upregulated and NF-κB activity was downregulated, whereas PP2A inhibitor okadaic acid (OA) restored NF-κB activity. Immunofluorescence and Western blots showed that OA treatment antagonized the decrease of p65 nuclear translocation caused by Notch-1 silencing. Moreover, OA treatment also upregulated MMP-2, MMP-9 and VEGF mRNA expression levels, indicating OA rescues Notch-1 silencing that caused low cell invasion. Taken together, our results suggest that Notch-1-activating PI3K/AKT/NF-κB pathway is PP2A dependent; PP2A may be a potential therapeutic target in breast cancer.


[PLACENTAL PATHOLOGY - IS IT JUST THE "BLACK BOX" OF PREGNANCY OR CAN IT SERVE AS A "CRYSTAL BALL" TO PREDICT RECURRENCE OF PREGNANCY COMPLICATIONS?]
Analysis of placental histopathology lesions may assist in a better understanding of the underlying mechanisms that lead to different clinical phenotypes in complicated pregnancy. Categorization of placental lesions provide us with a tool to determine the placental reaction and adaptation to abnormal placentation that occurs during pregnancy complications. Placental pathology has traditionally been the "black box" of pregnancy. The associations between placental histopathology and pregnancy complications have been studied comprehensively. After more than a decade of experience in collecting detailed placental pathological reports from various pregnancy complications, we looked for placental characteristics that could serve as predictors in patients with recurrence of pregnancy complications. It was found that in cases of preeclampsia, intrauterine growth restriction and preterm birth, prediction models involving placental pathology performed better than models based only on clinical factors. The placenta histopathology reports should be used not only as records from the "black-box of pregnancy" but more as records from the "crystal ball" for future pregnancies.


Arteriovenous anastomoses in the skin of seals. I. The Weddell seal Leptonychotes weddelli and the elephant seal Mirounga leonina (Pinnipedia: Phocidae).
The structure, distribution, density and innervation of arteriovenous anastomoses (AVAs) have been compared in the skin of Weddell and elephant seals, as part of a study of the structure and function of arteriovenous anastomoses in mammals. In both genera AVAs were coiled vessels with the segmental structure typical of "epithelioid" anastomoses and possessed a dense peripheral adrenergic innervation. In both Weddell and elephant seals there was no statistically significant difference between the mean density of AVAs in body skin and flipper skin. The majority, approximately 71% of AVAs occurred superficially in the dermis, fewer (23%) occurred in the deeper dermis, and 6% were present in the thick hypodermis (bubber). The density of AVAs in Weddell and elephant seals is approximately eight times greater than that reported in other animals and the superficial position of anastomoses over the whole of the body surface is characteristic of phocid seals. When open, AVAs in Weddell and elephant seals allow maximal heat loss from the skin surface by passing large volumes of blood into the superficial veins. AVAs in seals are important in dissipation of body heat, particularly when the animals are out of the water, and the entire surface area is thermoregulatory rather than specific regions such as the flippers.


Cervical HPV infection among HIV-infected prostitutes addicted to hard drugs.
An investigation into the prevalence of human papilloma virus (HPV) infection, abnormal cervical cytology and the relationship between HIV- and HPV infection was done in a group of intravenously (IV) and non-IV drug-using prostitutes. From July 1991 through May 1992, hard drug-addicted prostitutes attending a sexually-transmitted-disease (STD) clinic in Amsterdam were recruited. A questionnaire was administered to obtain demographic characteristics, and medical and STD history. Apart from routine STD examination, cervical scrapes for cytology and samples for HPV DNA detection by polymerase chain reaction (PCR) were collected. Some of the women included in this study also participated in HIV studies among drug users. Their data on HIV- and immunologic status could be combined. A total of 121 women entered the study; 25 women were HIV-seropositive, 44 women were HIV-negative, and the HIV status of 52 women was unknown. All 25 HIV-positive women had normal Pap smears, two of the 44 HIV-negative women had a Pap smear III A, and in the HIV-unknown group, two women with Pap III A and one with Pap III B were found. Eight of the 25 (32%) HIV-positive women were HPV DNA-positive, three of the 44 (7%) HIV-negative women and 10/52 (19%) of the HIV-unknown group. Logistic regression analysis showed that in the total group, presence or cervical HPV DNA was associated with HIV infection (order ratio [OR] for HIV-positives 7.8, 95% confidence interval [CI] 1.8 to 34.6) and with diagnosis of condylomata acuminata at entry to the study (OR 7.5, 95% CI 1.5 to 36.5).(ABSTRACT TRUNCATED AT 250 WORDS)


Radioembolization with (90)Y resin microspheres for intrahepatic cholangiocellular carcinoma: prognostic factors.
To investigate the prognostic factors that predict overall survival after radioembolization in patients with cholangiocellular carcinoma. The study comprised 16 patients who received radioembolization with Y(90) resin microspheres for cholangiocarcinoma. The statistical relationships between overall survival after radioembolization and age, number, dimension and fluorodeoxyglucose (FDG) avidity of liver lesions, liver tumor load, presence of extrahepatic metastases, and radiological response were analyzed. Mean 1.7 ± 0.1 GBq(90)Y microspheres were administered to a total of 16 patients (mean age: 55.37 ± 17.7; 8 males, 8 females). Mean AST, ALT, and total bilirubin levels were calculated as 35 ± 15, 40 ± 37 IU/L, and 0.77 ± 0.37 mG/dL, respectively. In 6 patients, 1 liver lesion was determined, in 2 patients ≤ 5, and in 8 patients >5, with dimensions varying between 12 and 120 mm. The liver lesions of 13 patients were FDG avid (mean SUVmax: 7.4 ± 2.2). Extrahepatic metastases were demonstrated in 5 patients. Tumor load of 4, 8, and 4 patients was calculated as <25, 25-50, and >50%, respectively. Five patients were responsive to treatment. During the follow-up period of 243 (range 98-839) days, 12 patients died. In Cox-regression analysis, FDG avidity (p = 0.02), the dimensions (p = 0.03) of the liver lesion, tumor load (p = 0.02), and radiological response (p = 0.01) were found to be statistically significant parameters predictive of overall survival after radioembolization (p = 0.006). FDG avidity and the dimension of the largest liver lesion, tumor load, and radiological response are prognostic factors in patients receiving radioembolization for cholangiocellular carcinoma. Patients with lower tumor load, FDG-negative tumors, and smaller tumors seem to survive longer after radioembolization.


Practical aspects of hydrophobic polycationic bactericidal "paints".
We previously discovered that coating solid surfaces with long-chained linear N-dodecyl,N-methyl-polyethylenimine makes them bactericidal and virucidal. In the present study, focusing on the use of this microbicidal paint to kill airborne Escherichia coli and Staphylococcus aureus, we have systematically investigated the dependence of this effect on the concentration and mode of application of the hydrophobic polycation, the number of coats, the nature of the solvent, and the presence of a dye in such paint. In addition, the latter's ability to be regenerated after use, stability upon repeated washings, and mammalian toxicity has been evaluated.


Novel gross deletion at the LHX4 gene locus in a child with growth hormone deficiency.
To identify and characterize a novel deletion at the LHX4 gene locus in a proband with growth hormone deficiency (GHD). Long range polymerase chain reaction (PCR) amplification was used to confirm the suspected deletion and to identify the rough locations of the end points. Sanger sequencing was carried out to identify the exact end points of the deletion. Suspected deletion was confirmed via long range PCR amplification. Sanger sequencing identified the end points of the deletion within three nucleotide repeat sequences ("CTT"). The total length of the deleted segment was 12 127 base pairs and it includes complete exon 5 and exon 6 of the LHX4 gene. Therefore the homeodomain motif coded by exons 4 and 5, might be affected. We have identified a novel deletion that spans exon 5 and exon 6 of the LHX4 gene that could have occurred via microhomology mediated non-recurrent rearrangement. The deletion characterized does not appear to have been reported before. To our knowledge this novel deletion is the first identified LHX4 variant from Sri Lanka and it explains the phenotype of the proband characterized by growth hormone deficiency, hypoplastic anterior pituitary and subsequent deficiency of thyroid stimulating hormone and adrenocorticotropic hormone (ACTH).


Obstructive sleep apnea manifesting as suspected angina: report of three cases.
To describe three cases of obstructive sleep apnea that resembled coronary artery disease and to suggest features that might distinguish these two syndromes. We present three detailed case reports of patients with severe obstructive sleep apnea and discuss similar cases from the literature. Two obese women and one obese man with previously undiagnosed obstructive sleep apnea had chest discomfort, episodic dyspnea, and palpitations, most prominent at night. All three patients had multiple cardiac risk factors and had previously undergone cardiac evaluations, including at least two prior cardiac catheterizations each. Repeated cardiac catheterization revealed less coronary occlusive disease than expected on the basis of the symptoms in all three patients and a small atrial septal defect in one patient. When reassessed, the medical histories suggested obstructive sleep apnea. Overnight polysomnography documented the presence of severe sleep apnea; the three patients had mean values of 56 disordered breathing events per hour and 44% minimal oxygen saturation. Although bi-level or continuous positive airway pressure yielded initial improvement, all patients had difficulty with routine use of this therapy after 1 1/2 years of follow-up. The initial manifestations of severe obstructive sleep apnea may simulate angina, suggest arrhythmia, or mimic heart failure. Failure to inquire about snoring and daytime somnolence in patients with chest pain may prevent the identification of clinically significant disordered breathing during sleep.


Identification of a novel 2026G-->C mutation of the MRP2 gene in a Japanese patient with Dubin-Johnson syndrome.
Dubin-Johnson syndrome is a recessive inherited disorder with conjugated hyperbilirubinemia caused by a dysfunction of multidrug resistance protein 2 (MRP2) on the canalicular membrane of hepatocytes. A mutational analysis of the MRP2 gene was carried out in three Japanese patients and their family members. In two patients, the homozygous mutations c.1901del67 and c,2272del168 were found. In the third patient, a -24C-->T polymorphism and the two mutations c.1901del67 and 2026G-->C were detected. The 2026G-->C mutation was a novel mutation in exon 16 affecting the conversion of Gly(676) to Arg(676) (G676R) in the MRP2 protein, and was not detected in fifty healthy volunteers. The G676R mutation was located in the Walker A motif of the first nucleotide binding domain in the MRP2 protein, and it was suggested that the mutation induced the dysfunction of the MRP2 protein. It was concluded that the compound heterozygosity of the two mutations of the MRP2 gene in the third patient contributed to the induction of hyperbilirubinemia in this case.


The effects of dexamethasone on in vitro collagen gene expression.
Glucocorticoids have been shown to be useful in the treatment of certain types of chronic liver disease both by inhibiting fibrosis and by improving liver function. We have previously demonstrated in an in vivo model of hepatic fibrogenesis that dexamethasone inhibits the synthesis of types I and IV collagen. In the present study we have evaluated the level of regulation responsible for the dexamethasone-induced changes in collagen gene expression in a defined in vitro system. Primary cultures of adult rat hepatocytes treated with and without dexamethasone under classical cell culture conditions or using defined media were evaluated for synthesis and abundance of procollagen and beta-actin mRNAs. Cells treated with dexamethasone had decreased types I and IV procollagen mRNA steady state levels due in part to diminished transcription rates of the genes. On the other hand, beta-actin mRNA levels were unaffected by dexamethasone. Transient expression experiments were performed to more precisely define the mechanism whereby dexamethasone affects type I procollagen gene transcription. The recombinant plasmid, pAZ1009, containing the mouse alpha 2(I) procollagen gene promoter linked to the chloramphenicol acetyltransferase gene, was transfected into mouse fibroblast cell lines. Cells transfected with the pAZ1009 plasmid in the presence of dexamethasone had a significant decrease in chloramphenicol acetyltransferase activity when compared to cells not exposed to dexamethasone. These data suggest that dexamethasone inhibits collagen synthesis through a direct effect on the collagen gene promoter and appears also to have a post-transcriptional effect on procollagen mRNA content.


Can we teach moderate intensity activity? Adult perception of moderate intensity walking.
To investigate how people determine the intensity of their physical activity, respond to instruction, and their understanding of moderate intensity walking. Experimental. Forty nine regular walkers had their walking speed, heart rate and rate of perceived exertion measured during their normal walking behaviour, when instructed to walk at a moderate intensity, and after provision of feedback on how to meet moderate intensity walking. Although moderate intensity walking was generally perceived as too low to be beneficial, walking speed was the best variable matched across all experiments for moderate intensity (83.7%, 67.3% and 93.9%), followed by heart rate, with a large proportion of participants responding favourably to instruction relating to heart rate and speed to meet moderate intensity walking. Rate of perceived exertion was a poor reflector of walking intensity. Most participants naturally selected a walking intensity that elicits moderate intensity and when instructed to walk at moderate intensity, the intensity is more vigorous. Attempting to match speed and heart rate limits for moderate intensity reduced the intensity perceived by participants.


[Bilateral sacroiliitis as an initial manifestation of sarcoidosis].
We report on the case of a 33-year old female patient with an acute case of a bilateral sacroileitis in sarcoidosis. Basing on this case report the various forms of joint sarcoidosis as well as differential diagnostic aspects are discussed.


Production of colony stimulating factor by EL-4 lymphoma cells stimulated with phytohemoagglutinin.
Murine EL-4 lymphoma cells when stimulated with optimal doses of phytohemoagglutinin (PHA) release colony stimulating factor (CSF) in the conditioned medium. CSF production depends on PHA and stops when the lectin is withdrawn. The production is dependent on protein synthesis and is not related with DNA replication. The CSF produced by El-4 cells stimulates murine bone marrow cells to differentiate in vitro into mature granulocytes. Unstimulated EL-4 cells do not produce CSF while its conditioned medium is able to inhibit EL-4 proliferation in vitro. Gel filtration chromatography of conditioned medium from PHA-stimulated EL4 cells yields a peak of activity corresponding to an apparent molecular weight of 20,000-25,000 daltons.


A case report of surgical repair of traumatic rupture of the pericardium and diaphragm.
A 55 year-old male with traumatic rupture of the pericardium, diaphragm and spleen, and with crush of the pancreas was successfully operated upon. The diagnosis of rupture of the diaphragm was done on the chest X ray on admission, and the rupture of the pericardium was diagnosed at the time of laparotomy and thoracotomy. The ruptured spleen and the crushed pancreas tail were removed, and the ruptured pericardium and diaphragm were closed successively.


Over-expression of p53 protein as an indicator of the malignant transformation in spiradenoma.
Malignant spiradenomas (spiradenocarcinomas) are exceedingly rare tumours of cutaneous adnexal origin, consisting of two components: benign--the pre-existent adenoma, and malignant--developing from the former part. We studied p53 protein expression in both compartments of three cases of malignant spiradenoma and compared these results with results obtained with eight cases of spiradenoma. Nuclear staining was consistently negative in all benign tumours, whilst in the cases of malignant transformation within spiradenoma p53 protein was present in the carcinomatous component, but the immunostaining remained negative in the benign counterpart of the tumour. In the zone of transition between both components of the spiradenocarcinomas p53 expression was positive in the cells with morphological atypia, providing clear discrimination. Thus, we conclude that the accumulation of p53 protein, which results from alterations in its turnover, accompanies the process of malignant transformation within long-standing spiradenomas.


Pancreatic mucin-producing adenocarcinoma associated with a pancreatic stone: report of a case.
We present an autopsy case of an 83-year-old Japanese man with a mucin-producing adenocarcinoma accompanied by pancreatolithiasis in the head of the pancreas. He suffered from obstructive jaundice and died of disseminated intravascular coagulation. He did not normally drink alcohol and had no history of chronic pancreatitis. The autopsy findings revealed a mucinous cystic tumor, composed of multiple dilatated branches, in the head of the pancreas. Histological examinations showed papillary adenocarcinoma, which scirrhously infiltrated the distal common bile duct with perineural invasion and lymph node involvement. He was thus diagnosed to have mucin-producing branch-type cancer in the head of the pancreas. The main pancreatic duct was dilated, and the residual pancreatic tissue showed moderate fibrosis and parenchymal atrophy. A stone was observed in a dilated branch of the primary lesion. To the best of our knowledge, there have only been five previously reported cases of mucin-producing tumor associated with pancreatolithiasis. Intraductal calcification is a major characteristic of chronic pancreatitis, but it is clinically important not to misdiagnose cancers associated with pancreatolithiasis such as chronic pancreatitis.


A new infiltration method for coating highly permeable matrices with compound materials for high-power isotope-separator-on-line production target applications.
A new infiltration coating method has been conceived for uniform and controlled thickness deposition of target materials onto highly permeable, complex-structure matrices to form short-diffusion-length isotope-separator-on-line (ISOL) production targets for radioactive ion beam research applications. In this report, the infiltration technique is described in detail and the universal character of the technique illustrated in the form of SEMs of several metal-carbide, metal-oxide and metal-sulfide targets for potential use at present or future radioactive ion beam research facilities.


Systemic inflammatory indices for predicting prognosis of myelofibrosis.
The impact of inflammatory markers such as systemic immune-inflammation (SII) index and systemic inflammation response index (SIRI) on myelofibrosis (MF) prognosis was evaluated for the first time in this study. Data from 60 patients diagnosed with MF between March 2011 and September 2022 were retrospectively analyzed. In addition to disease-related markers, the impact of SII and SIRI on prognosis was evaluated. In our study, the overall median survival (OS) was 64 months. OS was significantly shorter in patients older than 65 years, with high ferritin and lymphocyte levels, transfusion dependence at diagnosis, platelet count below 100 × 109/L, Hb level below 8 g/dl, and high risk according to the dynamic international prognostic scoring system (DIPSS)-Plus score. When these variables were included in the multivariate Cox regression model, it was found that being older than 65 years, having a high ferritin value, being at high risk according to the DIPSS-plus score and Hb values below 8 increased the risk of death. Platelet-to-lymphocyte ratio (PLR) and SII index were lower in patients with a fatal outcome. No statistically significant relationship was found between SIRI and mortality. The findings of this study showed that low PLR and high ferritin were associated with poor prognosis in MF. Elevated SII and SIRI, evaluated for the first time in patients with myelofibrosis, did not predict prognosis. Since non-inflammatory variables play a role in the pathogenesis of MF, bone marrow indicators and systemic inflammation indicators derived from hematologic parameters may not be accurate.


[Nonribosomal ribonucleoprotein particles in preparations of nonhistone proteins extracted from pigeon erythroblast chromatin].
Two proteins were isolated from preparations of weakly bound nonhistone proteins, obtained from highly purified chromatin with 0.35 M NaCl. These two protein residues from chromatin RNP-particles have the buoyant density of 1.41 g/cm3 as shown by centrifugation in CsCl gradients and contain heterogeneous fast labelling nuclear RNA. According to SDS polyacrylamide gel electrophoresis the molecular weights of these proteins are 70000 and 43000 daltons.


Efficacy of Different Precooling Agents and Topical Anesthetics on the Pain Perception during Intraoral Injection: A Comparative Clinical Study.
Topical anesthesia is widely advocated in pediatric dentistry practice to reduce pain and anxiety produced by administration of local anesthesia. Cryoanesthesia to lessen the injection pain has also been reported to be promising. However, sparse literature reports exist regarding clinical efficacy of these agents. The purpose of this study was to compare the efficacy of the refrigerant (1,1,1,3,3-pentafluoropropane/1,1,1,2-tetrafluo-roethane), benzocaine and ice on the pain perception during intraoral injection using visual analog scale (VAS) and sound, eye, motor (SEM) scale. In this Spit-mouth design study, a total of 160 patients between the age group of 5 and 8 years were selected and were randomly divided into two equal groups having 80 patients in each group. Ice cone has shown lower mean scores (p < 0.001) as compared to benzocaine and refrigerant whereas no significant difference was observed between refrigerant and benzocaine (p > 0.05) on both the scales. Ice cone had shown significantly higher efficacy as compared to benzocaine and refrigerant. How to cite this article: Lathwal G, Pandit IK, Gugnani N, Gupta M. Efficacy of Different Precooling Agents and Topical Anesthetics on the Pain Perception during Intraoral Injection: A Comparative Clinical Study. Int J Clin Pediatr Dent 2015;8(2):119-122.


Preferred methods of excess hair removal in pediatric patients with lung transplantation.
Hypertrichosis is common among recipients of lung transplantation taking cyclosporine and it poses a special psychosocial problem in children. Children and parents frequently inquire about methods of hair removal. We sought to determine preferred methods of hair removal in this population. We distributed a questionnaire to 104 pediatric recipients of lung transplantation. A total of 56 questionnaires (54%) were completed. Of respondents, 91% (51 of 56) experienced hypertrichosis, 75% (38 of 51) of whom attempted treatment. Depilatory cream was the most common hair removal technique (79%, 30 of 38). Shaving, particularly with an electric razor, received the highest ratings of both satisfaction and likelihood of future use. Generalizability is limited by the response rate. Preferred methods according to different hair locations were not evaluated. In our pediatric transplantation population, depilatory cream was the most commonly used treatment for hypertrichosis whereas electric shaving had the highest ratings of satisfaction and future use.


A NIR Fluorescent Probe Benzopyrylium Perchlorate-based for Visual Sensing and Imaging of SO2 Derivatives in Living Cells.
Endogenous sulfur dioxide (SO2), as a gas signal molecule, has a certain physiological functions. Understanding the role of endogenous SO2 in human physiology and pathology is of great significance to the biological characteristics of SO2,which bring challenges to develop fluorescent probes with excellent performance. Herein, we rationally designed and constructed a novel near-infrared bioprobe benzaldehyde-benzopyrylium (BBp) by employing the nucleophilic addition benzopyrylium perchlorate fluorophore and benzaldehyde moiety by means of C = C/C = O group that serves as both fluorescence reporting unit. Probe BBp exhibit excellent sensing performance with fluorescent "On - Off"rapid response (100 s) and long-wavelength emission (670 nm). With the treatment of HSO3-, the color of BBp solution obviously varies from purple to colorless, and the fluorescent color varies from red to colorless. By the fluorescence and colorimetric changes, probe BBp was capable of sensitive determination HSO3- with low limits of detection (LOD) of 0.43 μM, realizing visual quantitative monitoring SO2 derivative levels. Due to the low phototoxicity and good biocompatibility, it was successfully applied to monitor SO2 derivatives and fluorescence imaging in HepG2 and HeLa living cells. Hopefully, this work supplies a new strategy for designing NIR fluorescent probes for quantitative determination SO2 derivatives in biological samples.


Clopidogrel is not associated with increased bleeding complications after full-mouth extraction: A retrospective study.
To the authors' knowledge, the effect of clopidogrel on bleeding complications during full-mouth extraction has not been studied. The authors aimed to determine the safety of continued use of clopidogrel during full-mouth extraction. The authors performed a retrospective study of consecutive patients undergoing full-mouth extraction who were taking aspirin, clopidogrel, a combination of aspirin and clopidogrel, or neither. The main study outcomes in the 4 study groups were estimated blood loss, transfusion requirements, and complications. The authors also examined the correlation between the number of teeth extracted and estimated blood loss in various groups. Seventy-one patients underwent full-mouth extraction with removal of an average of 19 teeth. The authors excluded 3 patients owing to lack of data regarding blood loss. Of the remaining 68 patients, 25 were using aspirin, 12 were using clopidogrel, 9 were using both aspirin and clopidogrel, and 22 had discontinued the use of antiplatelets. There was no significant difference in the number of teeth extracted (P = .283) and estimated blood loss (P = .111) among the 4 groups. The authors found a significant moderate correlation between the number of teeth extracted and estimated blood loss in the group using aspirin (r = 0.537; P = .006) and in the group using clopidogrel, whether alone or in combination with aspirin (r = 0.535; P = .012), but not in the group who discontinued the use of antiplatelets. There was no need for blood transfusion in any patient. The results of this study provide limited evidence to suggest that continuation of clopidogrel during full-mouth extraction and preprosthetic surgery may be safe and does not appear to be associated with a significant risk of bleeding. Clopidogrel therapy during full-mouth extraction is not associated with significant bleeding complications and may be continued in patients who have a high risk of experiencing a cardiac event.


Measuring body composition in chronic heart failure: a comparison of methods.
Fat-free mass (FFM) is increasingly recognized as a systemic marker of disease severity in chronic organ failure and is an important target for physiologic and pharmacologic interventions to improve functional status. The aim of this study was therefore to evaluate two clinical methods to assess FFM in patients with chronic heart failure (CHF) using deuterium dilution (DEU) as reference and bromide dilution to assess the ratio between intracellular (ICW) and extracellular water (ECW) as potential confounder. Body composition was measured with dual-energy X-ray absorptiometry (DXA), bioelectrical impedance analysis (BIA) and DEU in 22 stable patients from our heart failure outpatient clinic and 24 healthy age matched controls. FFM values measured by DXA and DEU in patients (r = 0.92, SEE: 3.1 kg) and controls (r = 0.99, SEE: 1.3 kg) were strongly related. In both patients and controls, the inter method difference increased with higher values of FFM (DXA overestimating DEU). The ICW/ECW ratio was within the normal range and comparable between the groups. In patients, a highly significant correlation coefficient was found (r = 0.93, SEE 2.1 p = 0.01) between total body water (DEU) and height squared/resistance (Ht2/R). On multiple regression next to Ht2/R, body weight was an independent predictor of FFM(DEU) (r = 0.95, SEE 2.5 kg, p<0.001; TBWdeu = 0.528 Ht2/R + (0.182 weight) + 8.277). DXA and DEU are appropriate and interchangeable laboratory methods for assessment of FFM in clinically stable heart failure patients, however, overestimation of FFM(DXA) should be considered. BIA is a suitable clinical alternative for diagnostic purposes.


Experimental transmission of two Myxobolus spp. developing bisporogeny via tubificid worms.
Spores of Myxobolus cotti El-Matbouli and Hoffmann 1987 and M. cerebralis Hofer 1903 (fresh or after 5 months in mud) are taken in by tubifex worms and develop in their gut epithelium cells into actinosporea of the genus Triactinomyxon. Triactinomyxon deriving from M. cotti differ distinctly from those derived from M. cerebralis in morphology and the number of sporozoites in the epispore. It could be shown that Triactinomyxon spores infect fish either via the water (bullhead, rainbow trout) or by feeding of infected tubifex (rainbow trout), developing into Myxobolus spores in central nervous tissue (bullhead) or cartilage (rainbow trout). Fresh or ripened spores of M. cotti and M. cerebralis were not infectious for bullheads or rainbow trout, respectively. The results of our experiments confirm the hypothesis that the life cycle of M. cotti and M. cerebralis includes an intermediate host and a metamorphosis into actinosporea of the genus Triactinomyxon.


Spatial-temporal variations and influencing factors of air quality in China's major cities during COVID-19 lockdown.
To control the spread of COVID-19, the Chinese government announced a "lockdown" policy, and the citizens' activities were restricted. This study selected three standard air quality indexes, AQI, PM2.5, and PM10, of 2017-2021 in 40 major cities in six regions in China to analyze their changes, spatial-temporal distributions, and socioeconomic influencing factors. Compared with 2019, the values of AQI, PM2.5, and PM10 decreased, and the days with AQI levels "AQI ≤ 100" increased during the "lockdown" in 2020. Due to different degrees of industrialization, the concentration of air pollutants shows significant regional characteristics. The AQI values before and after the "lockdown" in 2020 show significant spatial autocorrelation, and the cities' AQI values in the north present high autocorrelation, and the cities in the south are in low autocorrelation. From the data at the national level, carbon emission intensity (CEI), per capita energy consumption (PEC), per capita GDP (PCG), industrialization rate (IR), and proportion of construction value added (PCVA) have the greatest impact on AQI. This study gives regulators confidence that if the government implements regionalized air quality improvement policies according to the characteristics of each region in China and reasonably plans socioeconomic activities, it is expected to improve China's air quality sustainably.


Multiple system atrophy-mimicking conditions: Diagnostic challenges.
Multiple system atrophy (MSA) is a relentless progressive disorder without effective treatment. Its accurate diagnosis is important for the management of individual patients and for the development of new therapeutic strategies. However, there are many disorders which can mimic MSA (so-called 'MSA look-alikes'), and the true rate for over- or under-diagnoses of MSA is not known, especially during the early course of disease when the disease is not fully developed yet. Herein, the authors review the neurodegenerative, genetic, and immunologic conditions that can mimic MSA and thus be part of the differential diagnosis of MSA. Clinicians should be aware of these conditions and be able to differentiate them by clinical features and laboratory findings.


Citrus fruits are rich in flavonoids for immunoregulation and potential targeting ACE2.
The most recent outbreak of 2019 novel coronavirus, named as COVID-19, caused pneumonia epidemic in Wuhan with 2121 deaths cases as of February 20th 2020. Identification of effective antiviral agents to combat the novel coronavirus is urgently needed. Citrus fruit peel or wild citrus are rich in flavonoids, and clinically documented for roles in relief of cough and promotion of digestive health. Therefore, citrus fruits are assumed to possess antivirus activities or enhance the host immunity. A previous study found that hesperetin could act as a high potent inhibitor of SARS-CoV 3CLpro. We determined six flavonoid compounds' content in three citrus species by using LC-MS technique. The content of naringin and naringenin was at higher levels in pummelo. Hesperetin and hesperidin were highly accumulated in mandarin and sweet orange. The subsequent in vitro and in vivo experiments indicated that naringin could inhibit the expression of the proinflammatory cytokines (COX-2, iNOS, IL-1β and IL-6) induced by LPS in Raw macrophage cell line, and may restrain cytokine through inhibiting HMGB1 expression in a mouse model. The results revealed that naringin may have a potential application for preventing cytokine storm. We simulated molecular docking to predict the binding affinity of those flavonoids to bind Angiotensin-converting enzyme 2 (ACE 2), which is a receptor of the coronavirus. Consideration of the potential anti-coronavirus and anti-inflammatory activity of flavonoids, the citrus fruit or its derived phytochemicals are promising in the use of prevention and treatment of SARS-CoV-2 infection.


A live imaging cell motility screen identifies prostaglandin E2 as a T cell stop signal antagonist.
The T cell migration stop signal is a central step in T cell activation and inflammation; however, its regulatory mechanisms remain largely unknown. Using a live-cell, imaging-based, high-throughput screen, we identified the PG, PGE(2), as a T cell stop signal antagonist. Src kinase inhibitors, microtubule inhibitors, and PGE(2) prevented the T cell stop signal, and impaired T cell-APC conjugation and T cell proliferation induced by primary human allogeneic dendritic cells. However, Src inhibition, but not PGE(2) or microtubule inhibition, impaired TCR-induced ZAP-70 signaling, demonstrating that T cell stop signal antagonists can function either upstream or downstream of proximal TCR signaling. Moreover, we found that PGE(2) abrogated TCR-induced activation of the small GTPase Rap1, suggesting that PGE(2) may modulate T cell adhesion and stopping through Rap1. These results identify a novel role for PGs in preventing T cell stop signals and limiting T cell activation induced by dendritic cells.


Identification of a C-glucuronide of delta6- tetrahydrocannabinol as a mouse liver conjugate in vivo.
Delta 6-Tetrahydrocannabinol-C-4-glucuronide was found in the livers of mice that had been administered delta 6-tetrahydrocannabinol. Thus, C-glucuronidation of a compound that contains a free hydroxyl group has been demonstrated in vivo.


Retracted: The Construction of National Image of China by English World Media in Public Health Emergencies.
[This retracts the article DOI: 10.1155/2022/9669941.].


Comparison of economic and patient outcomes with minimally invasive versus traditional off-pump coronary artery bypass grafting techniques.
Minimally invasive coronary artery bypass grafting (miniCABG) decreases in-hospital morbidity versus traditional sternotomy CABG. We performed a prospective cohort study (NCT00481806) to assess the impact of miniCABG on costs and metrics that influence quality of life after hospital discharge. One hundred consecutive miniCABG cases performed using internal mammary artery (IMA) grafting +/- coronary stenting were compared with a matched group of 100 sternotomy CABG patients using IMA and saphenous veins, both treating equivalent number of target coronaries (2.7 vs. 2.9), off-pump. We compared perioperative costs, time to return to work/normal activity, and risk of major adverse cardiac/cerebrovascular events (MACCE) at 1 year: myocardial infarction (elevated troponin or EKG changes), target vessel occlusion (CT angiography at 1 year), stroke, or death. For miniCABG, robotic instruments and stents increased intraoperative costs; postoperative costs were decreased from significantly less intubation time (4.80 +/- 6.35 vs. 12.24 +/- 6.24 hours), hospital stay (3.77 +/- 1.51 vs. 6.38 +/- 2.23 days), and transfusion (0.16 +/- 0.37 vs. 1.37 +/- 1.35 U) leading to no significant differences in total costs. Undergoing miniCABG independently predicted earlier return to work after adjusting for confounders (t = -2.15; P = 0.04), whereas sternotomy CABG increased MACCE (HR, 3.9; 95% CI, 1.4-7.6), largely from lower target-vessel patency. MiniCABG shortens patient recovery time, minimizes MACCE risk at 1 year, and showed superior quality and outcome metrics versus standard-of-care CABG. These findings occurred without increasing costs and with superior target vessel graft patency.


Malaria outbreak control in an African village by community application of 'deet' mosquito repellent to ankles and feet.
The malaria vector Anopheles arabiensis Patton (Diptera: Culicidae) shows a marked predilection (> 80%) for biting the ankles and feet of human subjects, as revealed by our previous observations at Malahlapanga in the Kruger National Park, South Africa. Topical application of insect repellent, 15% deet (N,N-diethyl-3-methylbenzamide), to feet and ankles reduced the overall biting rate of An. arabiensis by 69%. A focal malaria epidemic in Albertsnek village (25 degrees 33'S, 31 degrees 59' E) near the Mozambique border, following flooding during February 2000, provided an opportunity to apply these findings of operational research for outbreak containment. Twice-nightly topical application of deet to ankles and feet of Albertsnek inhabitants was followed by rapid restoration of preepidemic malaria incidence levels after one incubation period. This encouraging outcome should be attempted in other outbreak-prone settings where infective mosquito bites are sporadic and malaria has unstable endemicity.


Elephant resource-use traditions.
African elephants (Loxodonta africana) use unusual and restricted habitats such as swampy clearings, montane outcrops and dry rivers for a variety of social and ecological reasons. Within these habitats, elephants focus on very specific areas for resource exploitation, resulting in deep caves, large forest clearings and sand pits as well as long-established and highly demarcated routes for moving between resources. We review evidence for specific habitat exploitation in elephants and suggest that this represents socially learned cultural behaviour. Although elephants show high fidelity to precise locations over the very long term, these location preferences are explained neither by resource quality nor by accessibility. Acquiring techniques for exploiting specific resource sites requires observing conspecifics and practice and is evidence for social learning. Elephants possess sophisticated cognitive capacities used to track relationships and resources over their long lifespans, and they have an extended period of juvenile dependency as a result of the need to acquire this considerable social and ecological knowledge. Thus, elephant fidelity to particular sites results in traditional behaviour over generations, with the potential to weaken relationships between resource quality and site preferences. Illustrating the evidence for such powerful traditions in a species such as elephants contributes to understanding animal cognition in natural contexts.


Assessing fluvial organic carbon flux and its response to short climate variability and damming on a large-scale tropical Asian river basin.
Fluvial organic carbon (OC) transfer is an essential resource for downstream ecosystems. Multiple factors affect its transfer process, e.g., climate or anthropogenic activities. Quantifying OC fluxes with fine spatiotemporal resolution is challenging in anthropised catchments. This study aims to quantify daily OC dynamics and to assess the impacts of short climate variability and damming on OC spatiotemporal transfer processes in a large tropical Asian river basin (the Red River) for an extended period (2003-2013) by combining empirical equations with modelling outputs. Firstly, empirical equations for calculating dissolved (DOC) and particulate OC (POC) concentrations were calibrated based on in-situ sampling data. Then, simulated daily discharge (Q) and suspended sediment concentrations were used to quantify daily OC fluxes. Results show that the parameters of the DOC and POC equations well represent the subbasins characteristics, underlining the effects of soil OC content, mean annual Q and Chlorophyll a. DOC and POC exports reached 222 and 406 kt yr-1 at the basin outlet, accounting for 0.38 % of the total OC (TOC) exported by Asian rivers to the ocean. However, the specific yields of DOC (1.62 t km-2 yr-1) and POC (2.96 t km-2 yr-1) of the Red River basin were ~ 1.5 times those of other Asian basins. By comparing a reference scenario (without dams) to current conditions, we estimated 12 % and 88 % decreases in DOC and POC fluxes between 2008-2013 and 2003-2007, mainly due to damming. This study shows that climate variability may not impact OC dynamics in rivers as it explained <2 % of the variations. However, dam management, especially recent ones operating since 2008, deeply influences OC variations as the POC/TOC ratio decreased from 86 % to 47 %. Damming significantly decreased POC exports due to sediment retention, altering the equilibrium of OC cycling downstream, which may impact the food chain.


Valproic acid inhibits the angiogenic potential of cervical cancer cells via HIF-1α/VEGF signals.
Cervical cancer is one of the most prevalent malignancies in women worldwide. Therefore, the investigation about the molecular pathogenesis and related therapy targets of cervical cancer is an emergency. The objective of the present study is to investigate the effects of valproic acid (VPA), a histone deacetylase inhibitor, on the angiogenesis of cervical cancer. The effects and mechanisms of VPA on in vitro angiogenesis and vascular endothelial growth factor (VEGF) expression of human cervical cancer HeLa and SiHa cells were investigated. Our present study reveals that 1 mM VPA can significantly inhibit the in vitro angiogenic potential and VEGF expression of human cervical cancer HeLa and SiHa cells. Further, the transcription and protein levels of hypoxia inducible factor-1α (HIF-1α), and not HIF-1β, are significantly inhibited in VPA-treated cervical cancer cells. Over expression of HIF-1α can obviously reverse VPA-induced VEGF down regulation. VPA-treatment decreases the activation of Akt and ERK1/2 in both HeLa and SiHa cells in a time-dependent manner. The inhibitor of Akt (LY 294002) or ERK1/2 (PD98059) can inhibit VEGF alone and cooperatively reinforce the suppression effects of VPA on HIF-1α and VEGF expression. Collectively, our data reveal that the inhibition of PI3K/Akt and ERK1/2 signals are involved in VPA-induced HIF-1α and VEGF suppression of cervical cancer cells.


Hodgkin's disease complicating neuronal ceroid-lipofuscinosis.
This article reports the previously undescribed occurrence of Hodgkin's disease in a child with neuronal ceroid-lipofuscinosis.


Inferring Phylogenetic Relationships of Indian Citron (Citrus medica L.) based on rbcL and matK Sequences of Chloroplast DNA.
Phylogenetic relationships of Indian Citron (Citrus medica L.) with other important Citrus species have been inferred through sequence analyses of rbcL and matK gene region of chloroplast DNA. The study was based on 23 accessions of Citrus genotypes representing 15 taxa of Indian Citrus, collected from wild, semi-wild, and domesticated stocks. The phylogeny was inferred using the maximum parsimony (MP) and neighbor-joining (NJ) methods. Both MP and NJ trees separated all the 23 accessions of Citrus into five distinct clusters. The chloroplast DNA (cpDNA) analysis based on rbcL and matK sequence data carried out in Indian taxa of Citrus was useful in differentiating all the true species and species/varieties of probable hybrid origin in distinct clusters or groups. Sequence analysis based on rbcL and matK gene provided unambiguous identification and disposition of true species like C. maxima, C. medica, C. reticulata, and related hybrids/cultivars. The separation of C. maxima, C. medica, and C. reticulata in distinct clusters or sub-clusters supports their distinctiveness as the basic species of edible Citrus. However, the cpDNA sequence analysis of rbcL and matK gene could not find any clear cut differentiation between subgenera Citrus and Papeda as proposed in Swingle's system of classification.


High-Throughput DNA Assembly Using Yeast Homologous Recombination.
Yeast homologous recombination is a reliable, low-cost, and efficient method for DNA assembly. Using homology regions as short as 24 base pairs, constructs of up to 12 unique parts can be assembled into a diverse range of vectors. The simplicity and robustness of this protocol make it amenable to laboratory automation and high-throughput operations. Here we describe a high-throughput protocol to generate DNA parts through PCR, assemble them into a vector via yeast transformation, and "shuttle" the resulting plasmid constructs into E. coli for storage and propagation. Though this protocol is intended for high-throughput workflows, it can be easily adapted for bench-scale DNA assembly.


[Effects of p16 and GM-CSF combined gene therapy on immune response of tumor-bearing mice].
To investigate the effects of p16 and GM-CSF combined gene therapy on immune response of tumor-bearing mice (Renca). The model of renal tumor-bearing mice was constructed by subcutaneous injection of Renca cells. The tumor-bearing mice were divided into 5 groups at random three days after injection of Renca cells. Different groups of mice were given different treatments. The antitumor immune responses and the survival time of mice were tested. Histopathologic analysis of tumor tissue was done. Enhancement of antitumor immune responses and prolongation of survival period were observed more obviously in tumor-bearing mice after combined therapy than in those of the other four groups. p16 and GM-CSF combined gene therapy can enhance the antitumor immune responses of mice and inhibit the growth of pre-established renal cell carcinoma.


The draft genome dataset of the American cockroach, Periplaneta americana (Linnaeus, 1758) (Blattidae: Blattinae).
Periplaneta americana is a cosmopolitan pest cockroach endemic to tropical and subtropical climates. It occurs frequently in urban sewer and wastewater system and transit in human proximities, spreading pathogens that causes serious public health concerns such as asthma, allergies, and others. By using the Next-generation Sequencing (NGS) known as Illumina NovaSeq 6000, this article documents for the draft genome data set of P. americana collected in Penang Island, Malaysia. This article displays the pair-end 150 bp genome dataset and results on the sequence quality. This genome dataset presents the information for further understanding of P. americana populations at molecular level and the opportunity to develop effective control and management strategies for the species. This dataset is available under Sequence Read Archive (SRA) databases with the SRR23867103.


Is lipid peroxidation associated with DNA damage?
Specific binding to DNA of lipid peroxidation products was studied in rat hepatocytes labeled with [14C(U)]arachidonic acid after incubation at 37 degrees C either in the absence or in the presence of 200 microM FeSO4. The results obtained show that: (1) production of malondialdehyde-like thiobarbituric-reactive substances occurred in the absence of FeSO4 and was increased, albeit quite variably, by exposure to this pro-oxidant; (2) a low but appreciable binding of radioactivity to DNA and protein was constantly detected in 5 independent experiments; (3) there was no quantitative correlation between malondialdehyde formation and the amount of DNA-bound and protein-bound radioactivity, and any meaningful evidence of a GSH-depletion effect was absent. Taking into account the possible biosynthetic incorporation of radioactivity into DNA, the results of this study must be interpreted with caution, and solely as indicating that in the intact cell the covalent binding to DNA of reactive species generated by lipid peroxidation, if it occurs, should be minimal, corresponding in our experimental conditions approximately to 0.01 mumole of radioactive arachidonic acid per mole nucleotides.