Pepsin-trypsin digested gliadin treatment in intestinal cells.
Celiac disease (CD) is an intestinal autoimmune disorder developed in genetically susceptible individuals upon gluten ingestion. Gliadin is known to be the most immunogenic gluten component, which can activate the host immune response represented by NFkB activation and release of proinflammatory cytokines as IL8. However, many aspects of the involvement of gliadin in CD pathophysiology is not well understood yet. Lack of a CD animal model increases difficulty elucidating key steps in CD development, what increases the importance of in vitro experiments. Here we present a protocol for in vitro pepsin-trypsin digested gliadin (PTG) treatment for long term studies in HCT116 intestinal cell line.


Synaptic vesicles containing substance P purified by chromatography on controlled pore glass.
Subsynaptosomal particles containing the peptide, substance P, detected by radioimmunoassay were prepared by osmotic lysis of rat brainstem synaptosomes and chromatographed on a calibrated column of controlled pore glass beads of nominal pore size 300 nm. Immunoreactive substance P migrated on this column with particles of apparent mean diameter 117 nm. This particulate, immunoreactive substance P was indistinguishable from synthetic substance P by gel filtration and reverse-phase high pressure liquid chromatography. The specific activity of substance P with respect to protein in peak fractions was 140 pmoles/mg protein, 75-fold higher than in the crude homogenate. Particulate substance P was resistant to attack by endogenous proteases in a crude preparation. Depolarization of synaptosomes with 75 muM veratridine prior to vesicle purification decreased the recovery of particulate substance P 37%. This depletion was dependent on external calcium ions and was blocked by 1 muM tetrodotoxin. The foregoing properties of particulate substance P are consistent with its identification with the large, intraterminal substance P-positive vesicles seen by immunocytochemistry and suggest that these vesicles are involved in the release of substance P.


Plasma free fatty acid levels and the risk of ischemic heart disease in men: prospective results from the Québec Cardiovascular Study.
Insulin resistance, through numerous related disturbances in glucose and lipoprotein-lipid metabolism, is associated with an increased risk of ischemic heart disease (IHD). The purpose of the present study was to examine the relationship between increased plasma free fatty acid (FFA) concentrations, as a feature of the insulin resistance syndrome, and the risk of IHD in men. Analyses were carried out in a nested, case-control sample of men selected from a population of 2103 individuals without IHD at baseline among whom 114 developed IHD during a 5-year follow-up period. Incident IHD cases were matched with controls for age, body mass index, smoking habits and alcohol intake. Analyses were performed while excluding (88 cases and 98 controls) and including (103 cases and 99 controls) patients with type 2 diabetes. Among non-diabetic individuals, elevated plasma FFA concentrations (3rd tertile of the distribution) yielded a twofold increase in the risk of IHD (odds ratio [OR] 2.1, P=0.05) compared with lower plasma FFA levels (lowest tertile) after adjusting for non-lipid risk factors. Further adjustment for insulin, triglycerides, apolipoprotein B, HDL cholesterol and small dense LDL attenuated significantly the relationship between plasma FFA concentrations and the risk of IHD. High plasma FFA levels showed no synergism with selected features of the insulin resistance syndrome in determining the risk of IHD. Inclusion of diabetic subjects in the study did not improve FFA independent prognostic value to the risk of IHD. These results suggest that elevated plasma FFA concentrations are associated with an increased risk of IHD. However, a single fasting measurement of plasma FFA levels does not appear to improve our ability to predict IHD onset in men when information on other risk factors is considered.


Construction and one-step purification of Bacillus kaustophilus leucine aminopeptidase fused to the starch-binding domain of Bacillus sp. strain TS-23 alpha-amylase.
The starch-binding domain of Bacillus sp. strain TS-23 alpha-amylase was introduced into the C-terminal end of Bacillus kaustophilus leucine aminopeptidase (BkLAP) to generate a chimeric enzyme (BkLAPsbd) with raw-starch-binding activity. BkLAPsbd, with an apparent molecular mass of approximately 65 kDa, was overexpressed in Escherichia coli M15 cells and purified to homogeneity by nickel-chelate chromatography. Native PAGE and chromatographic analyses revealed that the purified fusion protein has a hexameric structure. The half-life for BkLAPsbd was 12 min at 70 degrees C, while less than 20% of wild-type enzyme activity retained at the same heating condition. Compared with the wild-type enzyme, the 60% decrease in the catalytic efficiency of BkLAPsbd was due to a 91% increase in K (m) value. Starch-binding assays showed that the K (d) and B (max) values for the fusion enzyme were 2.3 microM and 0.35 micromol/g, respectively. The adsorption of the crude BkLAPsbd onto raw starch was affected by starch concentration, pH, and temperature. The adsorbed enzyme could be eluted from the adsorbent by 2% soluble starch in 20 mM Tris-HCl buffer (pH 8.0). About 49% of BkLAPsbd in the crude extract was recovered through one adsorption-elution cycle with a purification of 11.4-fold.


Synthesis and magnetic properties of a [Ni(II)(TCNE)(NCMe)2-delta][BF4] magnet (Tc = 40 K).
The reaction of (NBu4)(TCNE) (TCNE = tetracyanoethylene) and [Ni(NCMe)6][BF4]2 in CH2Cl2 forms layered [Ni(TCNE)(MeCN)2-delta][BF4], a magnet ( Tc = 40 K) with a ferromagnetic interaction within Ni-mu 4-[TCNE](*-) layers, and a new general route to the preparation of [M(TCNE)(NCMe)2][anion] magnets has been identified.


Unconventional superconductivity and interaction induced Fermi surface reconstruction in the two-dimensional Edwards model.
We study the competition between unconventional superconducting pairing and charge density wave (CDW) formation for the two-dimensional Edwards Hamiltonian at half filling, a very general two-dimensional transport model in which fermionic charge carriers couple to a correlated background medium. Using the projective renormalization method we find that a strong renormalization of the original fermionic band causes a new hole-like Fermi surface to emerge near the center of the Brillouin zone, before it eventually gives rise to the formation of a charge density wave. On the new, disconnected parts of the Fermi surface superconductivity is induced with a sign-changing order parameter. We discuss these findings in the light of recent experiments on iron-based oxypnictide superconductors.


Whole body vibration of different frequencies inhibits H-reflex but does not affect voluntary activation.
This study aimed to investigate the effects of whole-body vibration (WBV) at a frequency spectrum from 20 to 50 Hz on the Hoffmann (H) reflex and the voluntary motor output of ankle plantar-flexor muscles. A single-group (n: 8), repeated measures design was adopted with four conditions: standing (no vibration), 20, 35 and 50 Hz, each lasting one minute. H-reflex of the soleus muscle, maximal voluntary contraction (MVC) and central activation ratio (CAR) of the plantar-flexors were evaluated before, 1 and 5 min after each frequency condition. H-reflex decreased by 36.7% at 20 Hz, by 28% at 35 Hz, and by 34.8% at 50 Hz after one minute from WBV compared to baseline. Neither MVC nor CAR changed after WBV at all frequency conditions. The short-term, acute inhibition of the H-reflex after WBV at 20, 35 and 50 Hz suggested that decreased excitability of spinal motoneurons is not frequency dependent. On the other hand, the lack of vibration induced effects on MVC and CAR indicated that a 1-min WBV stimulus is not sufficient to affect the voluntary motor output.


High stromal carbonic anhydrase IX expression is associated with nodal metastasis and decreased survival in patients with surgically-treated oral cavity squamous cell carcinoma.
Every year, approximately 25,000 patients are diagnosed with oral cavity squamous cell carcinoma (OCSCC) in the USA. The 5-year survival rate for OCSCC is approximately 40%. Intratumoral hypoxia confers poor prognosis and treatment failure but direct tumor oxygen measurement is challenging. Carbonic anhydrase IX (CAIX) is a marker of tissue hypoxia and we have recently shown that stromal CAIX is associated with reduced survival in patients with HPV-negative head and neck cancer. We examined the importance of this observation in OCSCC patients. We identified patients diagnosed and treated with OCSCC in Calgary (Alberta, Canada) between 1998 and 2005. Clinical and pathologic data were obtained from the Alberta Cancer Registry and chart review. Tissue microarrays (TMAs) were assembled from triplicate cores of archived tumor tissue. Stromal CAIX expression was assessed by quantitative immunohistochemistry (AQUA-HistoRx). The primary endpoint was disease-specific survival. We identified 102 patients with OCSCC; 87 patients had surgery as their primary treatment and adequate tumor tissue for TMA construction was available for all patients. CAIX expression was evaluable for 61 patients. High (top quartile) stromal CAIX expression was associated with significantly reduced 5-year disease-specific survival compared to low stromal CAIX expression (p<0.006). This study confirms our previously reported association between high stromal CAIX expression and significantly reduced overall survival in an independent, predominantly p16-negative, cohort of surgically treated OCSCC. Assessment of stromal CAIX expression could identify patients with the least favorable prognosis and inform therapeutic strategies in OCSCC.


Chemical optimization of artificial metalloenzymes based on the biotin-avidin technology: (S)-selective and solvent-tolerant hydrogenation catalysts via the introduction of chiral amino acid spacers.
Incorporation of biotinylated-[rhodium(diphosphine)]+ complexes, with enantiopure amino acid spacers, in streptavidin affords solvent-tolerant and selective artificial metalloenzymes: up to 91% ee (S) in the hydrogenation of N-protected dehydroamino acids.


Depression symptoms have a greater impact on the 1-year health-related quality of life outcomes of women post-myocardial infarction compared to men.
Several studies report that women with CAD have a poorer prognosis than men and suggest that depressive symptoms may be a contributing factor. The purpose of this study was to examine gender differences in depressive symptoms, as they relate to health-related quality of life outcomes following an AMI. Patients with documented AMI completed a questionnaire including the Short Form 36 physical (PCS), and mental component summary (MCS) scores, and Beck Depression Inventory at baseline and at 1 year after AMI admission. 486 (82%) patients completed the follow-up questionnaire. Females had significantly worse PCS and MCS scores at baseline and 1-year follow-up compared to males The mean 1-year Beck scores were significantly higher (p=0.01) for females (10.02+/-8.23) compared to males (7.78+/-8.01) indicating more reported depressive symptomatology. Multivariate analyses showed significant gender-related differences in the PCS scores at 1 year, but no gender-related differences in the 1-year MCS scores. These results suggest that gender differences in mental health at 1 year relate to gender-related differences at 1-year depression levels. The higher level of depression in women may be a consequence of gender differences in recovery patterns from an AMI and requires further investigation.


Lipoic acid reduces inflammation in a mouse focal cortical experimental autoimmune encephalomyelitis model.
Cortical lesions are a crucial part of MS pathology and it is critical to determine that new MS therapies have the ability to alter cortical inflammatory lesions given the differences between white and gray matter lesions. We tested lipoic acid (LA) in a mouse focal cortical EAE model. Brain sections were stained with antibodies against CD4, CD11b and galectin-3. Compared with vehicle, treatment with LA significantly decreased CD4+ and galectin-3+ immune cells in the brain. LA treated mice had fewer galectin-3+ cells with no projections indicating decrease in the number of infiltrating monocytes. LA significantly reduces inflammation in a focal cortical model of MS.


Coeliac disease in children with Type 1 diabetes mellitus: the effect of the gluten-free diet.
We assessed the frequency of coeliac disease in 281 children with Type 1 diabetes and the effect of gluten-free diet (GFD) in newly diagnosed cases. Serological screening was performed using anti-gliadin and anti-endomysium antibodies. Data were obtained about clinical symptoms, height and weight-for-height. A small intestinal biopsy was recommended to 18 patients (6.4%) with positive serological results and 12 children agreed. Nine of them had coeliac disease. Three out of nine coeliac children complained about gastrointestinal symptoms. On a GFD, the symptoms disappeared in two patients. Iron-deficiency anaemia was present in four subjects and disappeared in the three patients who accepted the GFD. In three patients (33%), coeliac disease was asymptomatic. Height and weight-for-height were in the normal range for all patients. For well-complying patients, there was a significant increase in height standard deviation at diagnosis and on follow-up (-0.28 vs. +0.35) (P = 0.03). Changes in weight-for-height were not significant (-4.0% vs. +1.4%) (P = 0.28). There was a trend to an improvement in HbA(1c) (8.0 vs. 7.3%) (P = 0.05). Serological screening is effective. There is a therapeutic benefit for some screening-detected patients, but confirmatory studies are needed.


Definitive radiotherapy for T1 and T2 squamous cell carcinoma of the tonsil.
To assess whether survival or local control of early squamous cell carcinoma of the tonsil has been compromised by a moderate-dose approach. Between 1970 and 1989, 185 patients with SCCa of the tonsil were seen at our institution. Fifty-three patients with T1 (30) and T2 (23) lesions treated with definitive radiotherapy were reviewed. Median follow-up was 60 months. The effects of total dose and site of the primary on survival and local regional control were analyzed. Three-year determinate survival was 77%. Mean total dose was 63.1 Gy. Site of the primary significantly affected survival (86% for fossa, 54% for pillars, p < 0.025). Local control at 2 years was 81% and was independent of dose > or = 63 Gy or site of the primary. Grade 4 complications defined by the RTOG/EORTC Acute Morbidity criteria occurred in three patients. Tumor doses on the order of 63 Gy or less result in excellent local control and survival rates for T1 and T2 carcinomas of the tonsil. Local control rates are better for fossa lesions than for pillar lesions.


Wetting phenomena on micro-grooved aluminum surfaces and modeling of the critical droplet size.
The behavior of water droplets on aluminum surfaces with parallel grooves tens of microns in width and depth is considered, and a mechanistic model is developed for predicting the critical droplet size-droplets at incipient sliding due to gravity. The critical droplet size is nearly 50% smaller on micro-grooved surfaces than on the same surface without micro-grooves. The application of existing models fails to predict this behavior, and a new model based on empiricism is developed. The new model provides reasonable predictions of the critical droplet size for a given inclination angle, advancing contact angle, and maximum contact angle. When the grooves are aligned parallel to gravity, the maximum apparent contact angle does not occur at the advancing front but rather along the side of the droplet because of contact-line pinning. Droplets on these surfaces are elongated and possess a parallel-sided base contour shape. Novel data are provided for droplets in a Wenzel state, a Cassie-Baxter state, and combined state on micro-grooved surfaces, and the ability of the empirical model to handle these variations is explored. These findings may be important to a broad range of engineering applications.


Deammonification process in municipal wastewater treatment: Challenges and perspectives.
The deammonification process has been proved to be an efficient nitrogen removal process in treating high NH4+-N concentration wastewater (sidestream deammonification). It is very hopeful to bring WWTP close to energy autarky. However, the feasibility of applying mainstream deammonification to sewage treatment need to be further explored. Therefore, this review attempts to give an overview of challenges in applying mainstream deammonification and to discuss the impacts of unfavorable conditions on main functional species. In addition, some novel control strategies to maintain the dominant position of desired species were summarized. Efficient solution to the conflict between AnAOB (Anaerobic ammonium-oxidizing bacteria) biomass retention and NOB (Nitrite oxidizing bacteria) wash out was also reviewed. Ultimately, we suggested further studies including effective improved process that achieve combination of autotrophy and organotrophy species based on the metabolic diversity of AnAOB.


Multichannel cochlear implantation: Utah-design.
The Utah-design multichannel cochlear implant consists of six intracochlear monopolar electrodes, one promontory electrode, and an indifferent electrode. Connection of the intracochlear system to the external sound processor is via a percutaneous pedestal system. Four of the intracochlear electrodes receive simultaneous stimulation. Twenty patients implanted at the University of Utah with more than 1 year of sound processor use were evaluated for the study. All patients wear their sound processors on a daily basis. Seven of the 20 are able to use the telephone without special devices. Nineteen patients were tested with open set CID sentences with an average 42.2% response. A comparison was made between live voice and taped voice open-set spondee word list performance, showing slightly better overall performance with live voice.


A designed P1 cysteine mimetic for covalent and non-covalent inhibitors of HCV NS3 protease.
The difluoromethyl group was designed by computational chemistry methods as a mimetic of the canonical P1 cysteine thiol for inhibitors of the hepatitis C virus NS3 protease. This modification led to the development of competitive, non-covalent inhibitor 4 (K(i) 30 nM) and reversible covalent inhibitors (6, K(i) 0.5 nM; and 8 K*(i) 10 pM).


[Contactless indicator of the rhythm of implanted pacemakers].
Non-content indicators of the rhythm are employed to exercise operative control over the functions of implanted cardiostimulators. The paper discusses issues concerned with the circuitry and the setup of subassemblies in such indicators, e.g. the sensor, amplifier, pulse expander, oscillator and output stage.


Mycophenolate mofetil in steroid-dependent idiopathic nephrotic syndrome.
Prospective studies have established the mycophenolate mofetil (MMF) efficiency in childhood idiopathic nephrotic syndrome (INS) but reports on the long-term outcome are lacking. Moreover, the search for factors influencing its efficiency would be useful to define its place among the other treatments. We performed a monocentric retrospective study including 96 children with steroid-dependent INS followed for 4.7 years (median) (IQ 3-6) after the onset of MMF treatment. The characteristics of responder patients (n = 74), as defined by a 50 % decrease of relapse rate and/or a 60 % decrease of steroid dose, and of non-responder patients (n = 22) were compared by univariate analysis and multivariate logistic regression. Withdrawal of prednisone was achieved in 48/96 patients after a median duration of 18.1 months (IQ 7.8-30.0) of MMF. Only 26/48 patients did not relapse under MMF alone. After MMF was stopped in these patients, only six remained in remission without any treatment at last follow-up. Responders had a shorter time to remission at the first flare (9.5 vs. 15 days, p = 0.02), a shorter disease duration prior to the onset of MMF (22.2 vs. 94.5 months, p = 0.001), and were younger at the MMF initiation (6.7 vs. 10.1 years, p = 0.02) than non-responder patients. The age of MMF initiation was an independent factor associated with efficiency (OR = 0.80, 95 % CI [0.69, 0.93], p < 0.01). MMF is more efficient in young patients treated early in the disease course. Nevertheless, MMF has no remnant effect while nearly all patients relapsed after withdrawal of the drug.


Quercetin: synergistic action with carboxyamidotriazole in human breast carcinoma cells.
Quercetin, a plant flavonoid, blocks signal transduction pathways by inhibiting 1-phosphatidylinositol 4-kinase (EC 184.108.40.206, PI kinase) and 1-phosphatidylinositol 4-phosphate 5-kinase (EC 188.8.131.52, PIP kinase), resulting in a reduction of inositol 1,4,5-trisphosphate (IP3) concentration which decreases the release of calcium from intracellular sources. Carboxyamidotriazole (CAI), a novel anticancer agent, inhibits calcium entry into cells. Because both drugs reduce cytosolic calcium levels, we tested the action of quercetin and CAI in human carcinoma cells. Human breast carcinoma MDA-MB-435 cells were grown in minimum essential medium with 10% fetal bovine serum. In growth inhibition assay the IC50s for quercetin and CAI were 55 and 4.8 microM, respectively; in clonogenic assay, 28 and 1.4 microM, respectively. When quercetin and CAI were added to the cultures, synergism was observed in isobolograms in growth inhibition and clonogenic assays. In growth inhibition assay, the best combination was 20 microM quercetin with 4 microM CAI; in clonogenic assay, 30 microM quercetin with 1.2 microM CAI. Since these drugs are in phase I trials the synergistic action of quercetin and CAI may be of interest in clinical trials for breast carcinoma.


Recent advances in lentiviral vectors for gene therapy.
Lentiviral vectors (LVs), derived from human immunodeficiency virus, are powerful tools for modifying the genes of eukaryotic cells such as hematopoietic stem cells and neural cells. With the extensive and in-depth studies on this gene therapy vehicle over the past two decades, LVs have been widely used in both research and clinical trials. For instance, third-generation and self-inactive LVs have been used to introduce a gene with therapeutic potential into the host genome and achieve targeted delivery into specific tissue. When LVs are employed in leukemia, the transduced T cells recognize and kill the tumor B cells; in β-thalassemia, the transduced CD34+ cells express normal β-globin; in adenosine deaminase-deficient severe combined immunodeficiency, the autologous CD34+ cells express adenosine deaminase and realize immune reconstitution. Overall, LVs can perform significant roles in the treatment of primary immunodeficiency diseases, hemoglobinopathies, B cell leukemia, and neurodegenerative diseases. In this review, we discuss the recent developments and therapeutic applications of LVs. The safe and efficient LVs show great promise as a tool for human gene therapy.


Calycosin ameliorates spinal cord injury by targeting Hsp90 to inhibit oxidative stress and apoptosis of nerve cells.
Zhenbao pill is effective in protecting against spinal cord injury (SCI). We attempt to explore the characteristics of calycosin (a main monomer of Zhenbao pill) in SCI and its relative mechanism. The target of calycosin was screened using pharmacological network analysis. The SCI cell model was constructed using hydrogen peroxide (H2O2), and the animal model was developed by compressing spinal cord with a vascular clamp. Flow cytometry was conducted to test reactive oxygen species (ROS) levels and cell apoptosis. Detection of malondialdehyde (MDA) activity and Superoxide dismutase (SOD) activity were performed using relative kits. Heat shock protein 90 (HSP90) was examined using western blot and quantitative real-time PCR. Motor function tests were carried out. The hematoxylin-eosin and Nissl staining were conducted. In SCI models, ROS, MDA, and cell apoptosis were elevated, SOD and HSP90 levels were restrained, while calycosin addition reversed the above results. Besides, calycosin application or HSP90 overexpression enhanced phosphorylation of protein kinase B (Akt) but weakened that of apoptosis signal-regulating kinase 1 (ASK1) and p38, while HSP90 inhibitor 17-AAG treatment restrained the above results. Meanwhile, the injection of calycosin improved the motor function in SCI model rats. Furthermore, the pathologic results also clarified the positive effect of calycosin on SCI. HSP90 was lowly expressed in SCI models. Calycosin alleviated SCI by promoting HSP90 up-regulation and inhibiting oxidative stress and apoptosis of nerve cells.


Closed-loop automated oxygen control in ventilated infants born at or near term: A crossover trial.
To determine if the use of closed-loop automated oxygen control (CLAC) reduced the incidence and duration of hypoxemic episodes (SpO2 < 92%) in ventilated infants born at or above 34 weeks of gestation. Infants were studied on two consecutive days for 6 h each day. They were randomised to receive standard care (manual oxygen control) or standard care with a CLAC system (automated oxygen control) first. Sixteen infants with a median (IQR) gestational age of 37.4 (36.6-38.8) weeks were studied at a median (IQR) postmenstrual age of 38.8 (37.4-39.8) weeks. During the automated oxygen control period, infants spent less time in hypoxemia (SpO2 < 92%) (p = 0.033), episodes of desaturation were shorter (p = 0.001), the time spent within target SpO2 range (92%-96%) was increased (p = 0.001), and the FiO2 delivery was lower (p = 0.018). The time spent in hyperoxemia (SpO2 > 96%) was reduced during automated oxygen control (p = 0.011), the episodes of hyperoxemia were of shorter duration (p = 0.008) and fewer manual adjustments were made to the FiO2 (p = 0.005). Closed-loop automated oxygen control in ventilated infants born at or near term was associated with a reduction in the incidence and duration of hypoxemic episodes with more time spent in the target oxygen range.


Ammoniacal silver staining of proteins: mechanism of glutaraldehyde enhancement.
When the conditions for detecting proteins by ammoniacal silver staining (B. R. Oakley, D. R. Kirsch, and N. R. Morris (1980) Anal. Biochem. 105, 361-363.) following gel electrophoresis were varied, it was noted that glutaraldehyde pretreatment was necessary for maximal staining, which could not be explained simply as the result of "fixation." Further studies indicated that glutaraldehyde enhancement of protein staining with this silver reagent was probably due to oxidation of the aldehyde groups by silver ions, resulting in metallic silver depositions within the gel which act as nucleation sites for additional metallic silver localization in the protein bands upon the addition of formaldehyde developer. This proposed mechanism is consistent with the Tollen's reaction, as well as some aspects of the photographic process. Consistent with this notion, silver-staining intensities are directly related to mole percentage lysine of various standard proteins.


Central nervous system neuron-glia co-culture models.
Glial cell activation plays an important role in the pathogenesis of various neurodegenerative disorders. This article presents a protocol for the preparation of cultures consisting of rat embryonic cortical neurons grown in the presence of cortical microglia, in which the glia are present in physical contact with the neurons or separated by a semi-permeable membrane barrier.


Comparative theoretical kinetics and thermodynamics study on high-energy insensitive explosive 1,1-diamino-2,2-dinitroethene synthesis.
Two synthesis methods were investigated in this study in order to explore feasible reaction pathways to obtain the target DADNE product: (1) the nitration of tetrahalogen ethene and (2) the reaction of acetamidine hydrochloride with dicarbonyl dichloride. Through theoretical simulation, the findings revealed that synthesis was possible, starting from acetamidine hydrochloride in a hydrated environment, followed by subsequent reaction routes via cyclization of the methoxy-substituted acetamidine anion intermediate with oxalyl chloride to form 2-methoxy-2-methyl-imidazolan-4,5-dione, acid-catalyzed synthesis of 2-methylene-imidazolan-4,5-dione, nitration using nitric acid to obtain 2-dinitromethylene-imidazolan-4,5-dione, and hydrolysis to produce 1,1-diamino-2,2-dinitroethene. A total energy of 1048.4 kJ mol(-1) was needed to carry out the reaction according to calculation of the energy barriers at each stage, as shown by the reaction profiles.


Alkyl peroxyl radical-scavenging activity of catechins.
Alkyl peroxyl radical (ROO.) generated from the reaction between 20 mM t-butyl hydroperoxide (t-BuOOH) and 200 microM hematin could kill E. coli. The minimum concentrations of catechins sufficient to rescue the bacteria treated with ROO. were found to be 70 microM for (-)-epicatechingallate, 100 microM for (-)-epicatechin and 125 microM for (+)-catechin. These values were comparable with the value of alpha-tocopherol, a typical ROO. scavenger. On the other hand, L-ascorbate and beta-carotene revealed about one tenth the scavenging activity of catechins. No scavenging activity was found for superoxide dismutase even at 86 mM. These facts indicate that catechins have high ROO. scavenging activity.


Genetically Determined Low-Density Lipoprotein Cholesterol and Risk of Subarachnoid Hemorrhage.
We evaluated whether genetically elevated low-density lipoprotein cholesterol (LDL-C) levels are associated with lower risk of intracranial aneurysms and subarachnoid hemorrhage (IA/SAH). We conducted a 2-sample Mendelian randomization (MR) study. Our primary analysis used the inverse-variance weighted method. In secondary analyses, we implemented the MR-PRESSO method, restricted our analysis to LDL-C-specific instruments, and performed multivariate MR. A 1-mmol/l increase in genetically instrumented LDL-C levels was associated with a 17% lower risk of IA/SAH (odds ratio = 0.83, 95% confidence interval = 0.73-0.94, p = 0.004). Results remained consistent in secondary and multivariate analyses (all p < 0.05). Our results provide evidence for an inverse causal relationship between LDL-C levels and risk of IA/SAH. ANN NEUROL 2022;91:145-149.


Present or absent on admission: results of changes in National Healthcare Safety Network surveillance definitions.
In January 2013, the National Healthcare Safety Network definition of "present on admission" was created. Using existing surveillance data from 2013, we identified health care-associated infections (HAIs) that met prior present on admission criteria but not the new definition. We identified a number of infections classified as HAI despite evidence that infection was clinically present on admission. These findings have important implications for states with mandatory HAI reporting using National Healthcare Safety Network definitions.


Different antitumor mechanisms of interferon-alpha in the treatment of hairy cell leukemia and renal cell cancer.
There is increasing evidence for the therapeutic effectiveness of Interferon-alpha (IFN-alpha) in malignant diseases. However, the antitumor mechanisms of IFN-alpha are not known. Using two examples, hairy Cell leukemia (HCL) and renal cell cancer (RCC), it is shown that the requirements for successful IFN-alpha therapy of HCL and RCC are different. In HCL low doses of IFN-alpha are sufficient to treat the disease. The reduction of hairy cells in peripheral blood is detectable within the first week of treatment. The endogenous IFN-alpha production in these patients is impaired as demonstrated by the lack of IFN-alpha induction and by low levels of 2-5 oligoadenylate synthetase in peripheral blood mononuclear cells. A possible reason for deficient endogenous IFN-alpha production is the lack of monocytes in HCL patients. It is likely that therapy with low doses of IFN-alpha substitutes for the endogenous IFN-alpha deficiency. In RCC comparatively high doses of IFN-alpha are necessary for a clinical response. There may be differences between the effectiveness of natural and recombinant alpha interferons. High doses given within a week seem to be more important than high single doses, which therefore suggests the need of daily treatment. Responses of RCC to IFN-alpha therapy are usually seen several months after the beginning of therapy. These differences in the effectiveness of IFN-alpha therapy for HCL and RCC suggest that IFN-alpha acts differently in the treatment of each disease.


Polymerization of Aniline in Tubular Cavities of the Crystalline Phase of Syndiotactic Polystyrene: Proposal of a Preparation Method of Sophisticated Polymer Composites.
Syndiotactic polystyrene (SPS) has a unique crystalline phase, named ε, that has a tubular cavity inside. We connected these cavities by optimizing the solvent used to process the films and to polymerize aniline within these channeling cavities only by immersing the films in degassed hydrochloric acid solutions of ammonium persulfate. We succeeded in fixing pentameric to octameric oligoaniline in the cavities of the SPS ε crystalline phase. This is a new and sophisticated preparation method of polymer composites between SPS and linear oligomers/polymers within its long-connected tubular cavities.


Longitudinal changes in swallowing function after surgery and proactive swallowing therapy for oral cancer.
This study aimed to describe and explore the longitudinal changes in swallowing function among patients with oral cancer who underwent surgery and proactive swallowing therapy from baseline to 1-year postoperation. We retrospectively studied 118 patients over a 4.5-year duration. Swallowing functional assessment including 10-item Eating Assessment Tool (EAT-10), Functional Oral Intake Scale (FOIS), M. D. Anderson Dysphagia Inventory, and Modified Barium Swallow Impairment Profile (MBSImP™) was performed at baseline, 1-month, 6-month, and 1-year postoperatively. All swallowing parameters worsened 1-month postoperation. EAT-10, FOIS, and MBSImP™ oral and pharyngeal impairment scores improved significantly compared with 1-month postoperation at 6 months. Other swallowing parameters, except for weight, did not differ significantly from baseline at 6 months. The rate of tube-feeding dependency was 11.5% and 5.6% at 1 and 6 months postoperation, respectively. Periodic swallowing functional assessments help delineate the longitudinal changes in swallowing functional outcomes.


High concentrations of plasma brain-derived neurotrophic factor in methamphetamine users.
Methamphetamine is a highly addictive drug that has a neurotoxic effect on the brain. A growing body of evidence suggests that brain-derived neurotrophic factor (BDNF) is associated with addictive behavior. The present study investigated the changes in plasma BDNF concentration that were induced by chronic methamphetamine use. Using an enzyme-linked immunosorbent assay (ELISA), we measured peripheral BDNF levels in methamphetamine users and in a control group. The plasma BDNF concentrations of methamphetamine users were significantly higher compared with those of controls (2536.3 pg/ml versus 1352.6 pg/ml). This finding suggests that BDNF plays some role in the neurotoxicity of methamphetamine.


Real World Outcomes versus Clinical Trial Results of Durvalumab Maintenance in Veterans with Stage III Non-Small Cell Lung Cancer.
One year of durvalumab following concurrent chemoradiotherapy improves progression-free (PFS) and overall survival (OS) for patients with stage III non-small cell lung cancer (NSCLC). However, the real-world efficacy of durvalumab has not been determined. We conducted a multi-center observational cohort study across the Veterans Health Administration, including patients with stage III NSCLC who received concurrent chemoradiotherapy and durvalumab, compared to patients who received concurrent chemoradiotherapy alone. Kaplan-Meier and Cox regression approaches were used to identify factors associated with PFS and OS. We calculated a hazard ratio and efficacy-effectiveness factor to compare OS of veterans to the referenced clinical trial population. A total of 1006 patients with stage III NSCLC who received concurrent chemoradiotherapy and at least one dose of durvalumab from November 2017 to April 2021 were compared to 989 patients who received concurrent chemoradiotherapy alone from January 2015 to December 2016. Adjuvant durvalumab was associated with higher PFS (HR 0.62, 95% CI 0.55-0.70, p < 0.001) and OS (HR 0.57, 95% CI 0.50-0.66, p < 0.001). OS was shorter in veterans compared to PACIFIC (HR 1.24, 95% CI 1.03-1.48, p = 0.02: EE gap 0.73). OS of veterans with stage III NSCLC treated with adjuvant durvalumab is improved compared to a modern comparator but is reduced compared to the PACIFIC population.


Efficacy of Seprafilm for reducing reoperative risk in pediatric surgical patients undergoing abdominal surgery.
The safety and efficacy of Seprafilm (Genzyme Corporation, Cambridge, Mass) in adult surgery patients have been established. The aim of this study was to evaluate the safety and efficacy of Seprafilm in pediatric surgical patients. One hundred twenty-two pediatric abdominal surgery patients were enrolled. Sixty-seven patients received Seprafilm application. Of these patients, 18 again received Seprafilm at abdominal closure during a second surgery, and of the 18, 4 received Seprafilm at closure after a third surgery. Of the 55 control patients who did not receive Seprafilm, 14 had a second surgery, and of these 14 patients, 4 had a third surgery. Adverse events, operation time, and blood loss were compared with assessed Seprafilm safety. Seprafilm efficacy evaluations included incidence and severity of adhesions in those patients who required relaparotomy. The incidence (Seprafilm, 40.9%; control, 82.4%) and severity (Seprafilm: 59.1%, grade 0; control: 17.6%, grade 0) of adhesions under the abdominal incision site were significantly reduced in the Seprafilm group (P = .007 and P = .0009, respectively). In addition, mean relaparotomy operation time was significantly shorter for Seprafilm patients (P = .004). At relaparotomy, blood loss/body weight ratio for Seprafilm patients compared with control patients showed a trend toward but did not reach significance (P = .09). Decreased incidence and severity of postsurgical adhesions with Seprafilm in pediatric patients may lead to reduction of the risks associated with subsequent operation.


Gene(s) affecting the expression of Qa-1.
Lymphocytes from different strains vary in their expression of antigenic determinants encoded by the Qa1 locus. Thus, a lower percentage of cells from strains bearing H-2Dk are lysed in antibody-mediated cytotoxic tests. These cells fail to completely absorb anti-Qa1 activity from antisera. The unexpressed determinants are present in unactivated cells when subcellular fractions are tested and are detectable on the membrane of mitogen-activated lymphocytes. The gene(s) controlling this phenomenon are dominant and map to a region between H-2S and Tla.


A multicentre, prospective, double-blind study comparing the accuracy of autoantibody diagnostic assays in myasthenia gravis: the SCREAM study.
Laboratory determination of autoantibodies against acetylcholine receptor (AChR), muscle-specific kinase (MuSK) and other autoantigens have been integrated into the diagnosis of myasthenia gravis (MG). However, evidence supporting the selection of methodologies is lacking. In this prospective, multicentre cohort study, we recruited patients with suspected MG to evaluate the diagnostic accuracy of cell-based assay (CBA), radioimmunoprecipitation assay (RIPA) and enzyme-linked immunosorbent assay (ELISA) in detecting AChR and MuSK autoantibodies. This study is registered with www.clinicaltrials.gov, number NCT05219097. 2272 eligible participants were recruited, including 2043 MG, 229 non-MG subjects. AChR antibodies were detected in 1478, 1310, and 1280 out of a total of 2043 MG patients by CBA, RIPA, and ELISA, respectively; sensitivity, 72.3% (95% CI, 70.3-74.3), 64.1% (95% CI, 62.0-66.2), 62.7% (95% CI, 60.5-64.8); specificity, 97.8% (95% CI, 95.0-99.3), 97.8% (95% CI, 95.0-99.3), 94.8% (95% CI, 91.9-97.7). MuSK antibodies were found in 59, 50, and 54 from 2043 MG patients by CBA, RIPA and ELISA, respectively; sensitivity, 2.9% (95% CI, 2.2-3.7), 2.4% (95% CI, 1.8-3.2), 2.6% (95% CI, 2.0-3.4); specificity, 100% (95% CI, 98.4-100), 100% (95% CI, 98.4-100), and 99.1% (95% CI, 96.9-99.9). The area under the curve of AChR antibodies tested by CBA was 0.858, and there were statistical differences with RIPA (0.843; p = 0.03) and ELISA (0.809; p < 0.0001). CBA has a higher diagnostic accuracy compared to RIPA or ELISA in detecting AChR and MuSK autoantibodies for MG diagnosis. New Terrain Biotechnology, Inc., Tianjin, China.


Using the EDAC test to monitor abstinence and relapses during outpatient treatment.
The main objective of this study is to show the performance of the EDAC test in monitoring alcohol consumption during outpatient treatment. The EDAC is a new approach that uses routine laboratory tests to identify binge drinking as well as chronic drinking. The overall diagnostic performance of the EDAC fluctuates around 80 to 90% for both specificity and sensitivity. Close to two thousand subjects have been tested by the EDAC since the early eighties; 300 of these were patients undergoing treatment at different institutions across the U.S. This article selected five case studies to represent examples of classical drinking behaviors encountered in most outpatient clinics. The first four cases illustrate the use of the EDAC alone and the last case represents the use of the EDAC combined with CDT. These five case studies illustrate the use of the EDAC to detect relapse episodes, to monitor abstinence during outpatient treatment and to recognize a slip early enough to prevent more severe drinking. The use of biomarkers to monitor drinking behavior in alcohol dependent patients is gaining popularity because they provide objective information on a patient's drinking status when used as an adjunct to self-report.


Proteomic analysis of bacterial communities associated with atopic dermatitis.
Atopic dermatitis (AD) is a relapsing, chronic, and inflammatory skin disorder. Its causes remain unclear. Here, we reported the first proteome study of the bacterial community in AD patients. Bacterial community in 7 patients and 1 healthy control using bottom-up proteomics were examined starting with in-solution digestion followed by purification steps with subsequent analysis using LC-MS/MS and ended with data processing and bioinformatic analysis. Overall, great bacterial changes between patient samples and healthy one were noticed with the presence of Staphylococcus aureus, Aeromonas hydrophila, and Shewanella species, and others that were present uniquely in patient samples suggesting their role in AD. Additionally, detection of some important proteins that trigger bacterial pathogenesis and the immune system such as enolase, glyceraldehyde-3-phosphate, Chaperone proteins DnaK and HtpG beside protein pathways needed for bacterial growth and pathogenesis like chaperones and folding catalysts; and Energy metabolism. These new findings of the microbiome and detected proteins could start a new era of proteomics to study the bacterial community as a whole and detect the way it interacts with each other and with the host. SIGNIFICANCE: This paper would represent a reference work for investigations on microbiota that present on AD, from both a microbiological and a functional proteomic point of view. We focused on analysisng bacteria community and proteins produced and its role in the disease, highlighting some functional characteristics of certain proteins and discussing its potential role in AD.


De novo intestine-specific transcriptome of the brown planthopper Nilaparvata lugens revealed potential functions in digestion, detoxification and immune response.
The brown planthopper (Nilaparvata lugens, BPH) is the most serious rice plant pests in Asia. In this study, we performed transcriptome-wide analysis on BPH intestine. We obtained more than 26 million sequencing reads that were then assembled into 53,553 unigenes with a mean size of 388 bp. Based on similarity search with the nucleotide sequences available at NCBI, BPH intestine-specific transcriptome analysis identified 21,405 sequences. Assembled sequences were annotated with gene description, gene ontology and clusters of orthologous group terms. The digestion-, defense- and xenobiotic metabolism-related genes were abundantly detected in the transcripts from BPH intestine. Many novel genes including 33 digestion-related genes, 25 immune responsive genes and 27 detoxification-related genes are first reported here. We investigated the gene expression patterns at the transcript levels in different tissues by quantitative real-time PCR analysis, which revealed that some genes had intestine-specific expression, implicating their potential significance for BPH management.


COVID-19 vaccination status, side effects, and perceptions among breast cancer survivors: a cross-sectional study in China.
Breast cancer is the most prevalent malignancy in patients with coronavirus disease 2019 (COVID-19). However, vaccination data of this population are limited. A cross-sectional study of COVID-19 vaccination was conducted in China. Multivariate logistic regression models were used to assess factors associated with COVID-19 vaccination status. Of 2,904 participants, 50.2% were vaccinated with acceptable side effects. Most of the participants received inactivated virus vaccines. The most common reason for vaccination was "fear of infection" (56.2%) and "workplace/government requirement" (33.1%). While the most common reason for nonvaccination was "worry that vaccines cause breast cancer progression or interfere with treatment" (72.9%) and "have concerns about side effects or safety" (39.6%). Patients who were employed (odds ratio, OR = 1.783, p = 0.015), had stage I disease at diagnosis (OR = 2.008, p = 0.019), thought vaccines could provide protection (OR = 1.774, p = 0.007), thought COVID-19 vaccines were safe, very safe, not safe, and very unsafe (OR = 2.074, p < 0.001; OR = 4.251, p < 0.001; OR = 2.075, p = 0.011; OR = 5.609, p = 0.003, respectively) were more likely to receive vaccination. Patients who were 1-3 years, 3-5 years, and more than 5 years after surgery (OR = 0.277, p < 0.001; OR = 0.277, p < 0.001, OR = 0.282, p < 0.001, respectively), had a history of food or drug allergies (OR = 0.579, p = 0.001), had recently undergone endocrine therapy (OR = 0.531, p < 0.001) were less likely to receive vaccination. COVID-19 vaccination gap exists in breast cancer survivors, which could be filled by raising awareness and increasing confidence in vaccine safety during cancer treatment, particularly for the unemployed individuals.


Sulfonylureas and cardiovascular effects: from experimental data to clinical use. Available data in humans and clinical applications.
33 years after the UGDP study, the question of deleterious effects of the sulfoylurea (SU) is still raised. We have made a systematic review of the literature from experimental studies to clinical and epidemiological studies. The main molecule studied is glibenclamide (GB). In vitro and in animal studies, GB is both deleterious for ischemic preconditionning (IPC) and protective for arrhythmia during acute ischemia. Glimepiride (GM) and gliclazide (GCZ) do not seem to have effect on IPC. These effects have been few studied in diabetic animals. In human, according to the investigations used, the GB seems nil or suppressing for IPC, it seems elsewhere decreases ventricular arrhythmias during periods of acute ischemia. It is possible that these two actions account for the non-appearance of concordant deleterious effects between short and long-term studies. With regards to other drugs, only the GM has been specifically studied in human and appears to be nil on IPC. The only prospective clinical study available, although not having for objective to answer to this question, is the UKPDS study. This trial demonstrates the absence of deleterious cardiac effects of GB compared to chlorpropamide and particularly compared to insulin. In conclusion, in experimental studies the cardiac effects of SU differ: both deleterious and protective for GB, nil for GM and GCZ on IPC. In all cases the clinical consequences seems to be nil.


Systematic Review and Meta-analysis: Screening Tools for Attention-Deficit/Hyperactivity Disorder in Children and Adolescents.
This systematic review and meta-analysis aimed to determine the accuracies of a broad range of screening tools for attention-deficit/hyperactivity disorder (ADHD) in children and adolescents, and to compare the diagnostic accuracy of tools between population-based and clinical/high-risk samples, and across reporters. MEDLINE, PsycINFO, EMBASE, and PubMed were searched up until February 20, 2020, with no language restrictions. Studies reporting diagnostic accuracy of a screening tool against a diagnosis of ADHD in children and adolescents <18 years of age were eligible for inclusion. Meta-analyses were undertaken to provide pooled estimates of the area under the curve (AUC), and sensitivity and specificity of groups of measures. A total of 75 studies published between 1985 and 2021 reporting on 41 screening tools that were grouped into 4 categories (Achenbach System of Empirically Based Assessment [ASEBA], DSM-IV symptom scales, SDQ, and Other Scales) were retained. The pooled AUC for studies using a combined ADHD symptoms score was 0.82 (95% CI = 0.78-0.86), although this varied considerably across reporters (0.67-0.92) and populations (CI = 0.60-0.95). None of the measures met minimal standards for acceptable sensitivity (0.8) and specificity (0.8). Most tools have excellent overall diagnostic accuracy as indicated by the AUC. However, a single measure completed by a single reporter is unlikely to have sufficient sensitivity and specificity for clinical use or population screening.


Pharmacological effects of vinorelbine on body temperature and locomotor activity circadian rhythms in mice.
The effects of vinorelbine (VRL) on the circadian rhythms in body temperature and locomotor activity were investigated in unrestrained B6D2F1 mice implanted with radio-telemetry transmitters. A single intravenous VRL dose (24 or 12 mg/kg) was given at 7 h after light onset (HALO), a time of high VRL toxicity, and resulted in transient suppression of temperature and activity circadian rhythms in mice kept in light-dark (LD) 12h: 12h. Such suppression was dose-dependent. It occurred within 1-5 d after VRL dosing. Recovery of both rhythms was partially complete within 5 d following the high dose and within 2 or 3 d after the low dose and was not influenced by suppression of photoperiodic synchronization by housing in continuous darkness. Moreover, VRL induced a dose-dependent relative decrease in amplitude and phase shift of the temperature circadian rhythm. The mesor and amplitude of the activity rhythm were markedly reduced following the VRL administration. The relevance of VRL dosing time was studied in mice housed in LD 12h:12h. Vinorelbine was injected weekly (20 mg/kg/injection) for 3 wk at 6 or 18 HALO. Vinorelbine treatment ablated the rest-activity and temperature rhythms 3-6d after each dose, with fewer alterations after VRL dosing at 18 HALO compared to 6 HALO, especially for the body temperature rhythm. There was at least partial recovery 1 wk after dosing, suggesting the weekly schedule of drug treatment is acceptable for therapeutic purposes. Our findings demonstrate that VRL can transiently, yet profoundly, alter circadian clock function. Vinorelbine-induced circadian dysfunction may contribute to the toxicokinetics of this and possibly other anticancer drugs.


Clotting, microembolism, and inhibition of fibrinolysis in adult respiratory distress.
Clinical and autopsy studies have shown an association between clotting, microembolism, and inhibition of fibrinolysis and respiratory distress after trauma or sepsis. Prophylaxis and treatment with the aim of decreasing the deposition of fibrin in the lungs were associated with a large decrease in the incidence and death rate of this syndrome. Small fibrin degradation products (peptides) are accumulated in the lungs and are only slowly cleared from this organ, especially during states of inhibition of fibrinolysis. These peptides may contribute to the pulmonary damage in several ways. As well as having a direct effect on the endothelium, they act by interfering with other vasoactive substances as bradykinin, histamine, and products of the arachidonic acid cascade. Products of the cyclooxygenase pathway such as thromboxane A2 play a major role in early microembolism, whereas lipoxygenase products seem to be involved in later stages. Pulmonary microembolism thus seems to be one important, but certainly not the only, pathogenetic factor in acute "idiopathic" respiratory failure. Other factors, such as pulmonary contusion, aspiration of gastric contents or blood, or oxygen toxicity, might well be contributory in some cases. Pulmonary microemboli containing fibrin and leukocytes are probably also involved as contributory agents in some cases in the large group of acute respiratory failures due to "known factors."


Phosphorylation of surface E-selectin and the effect of soluble ligand (sialyl Lewisx) on the half-life of E-selectin.
E-selectin (ELAM-1) is an adhesion molecule for leukocytes that is transiently expressed on endothelial cells. Following cell surface expression of E-selectin on human umbilical vein endothelial cells (HUVEC) stimulated with tumor necrosis factor, the induced E-selectin molecules are rapidly degraded. The kinetics of turnover of surface disposed E-selectin were investigated. The rapid disappearance of surface E-selectin is temperature dependent and sensitive to the lysosomotropic agent chloroquine. The half-life of E-selectin is not affected by inclusion of soluble sialyl Lewis x (sLex) ligands in the medium. Surface E-selectin is phosphorylated on one or more serine residues, but this modification is not obviously related to internalization.


On the relative importance of spatial and timbral fidelities in judgments of degraded multichannel audio quality.
Mean opinion score ratings of reproduced sound quality typically pool all contributing perceptual factors into a single rating of basic audio quality. In order to improve understanding of the trade-offs between selected sound quality degradations that might arise in systems for the delivery of high quality multichannel audio, it was necessary to evaluate the influence of timbral and spatial fidelity changes on basic audio quality grades. The relationship between listener ratings of degraded multichannel audio quality on one timbral and two spatial fidelity scales was exploited to predict basic audio quality ratings of the same material using a regression model. It was found that timbral fidelity ratings dominated but that spatial fidelity predicted a substantial proportion of the basic audio quality.


On-site quantitation of arsenic in drinking water by disk solid-phase extraction/mobile X-ray fluorescence spectrometry.
A rapid and simple method was developed for As determination in drinking water by solid-phase extraction (SPE)/mobile X-ray fluorescence (XRF) spectrometry. A 50 mL aqueous sample was adjusted to pH 3 with dilute hydrochloric acid, and then passed through a Ti and Zr-loaded carbon disk (TiZr-CD) to pre-concentrate the As. The SPE disk was adhered to an acrylic plate with cellophane tape, and then examined by mobile XRF spectrometry. The TiZr-CD adsorbed inorganic As (as As(III) and As(V)) and organic As (as methyl, phenyl and aromatic arsenic compounds) from water. The As calibration curve had good linearity over the range of 0.5-5 μg, and the limit of detection was 0.10 μg (2.0 μgL(-1) in As concentration). The concentrations of As in well water samples were determined using the proposed method were similar to results obtained from atomic absorption spectrometry. The proposed method did not require a power supply or a toxic solution and/or gas in any analytical step, therefore it is suitable for the on-site determination of As in drinking water.


Genomic characterization of three bacteriophages infecting donkey-derived Escherichia coli.
Bacteriophages are an important source of novel genetic diversity. Sequencing of phage genomes can reveal new proteins with potential uses in phage therapy and help unravel the diversity of biological mechanisms by which phages take over the machinery of the host during infection. To expand the available collection of phage genomes, we have isolated, sequenced, and assembled the genome sequences of three phages that infect three pathogenic Escherichia coli strains: vB_EcoM_DE15, vB_EcoM_DE16, and vB_EcoM_DE17. Morphological characterization and genomic analysis indicated that all three phages were strictly lytic and free from integrases, virulence factors, toxins, and antimicrobial resistance genes. All three phages contained tRNAs, and especially, vB_EcoM_DE17 contained 25 tRNAs. The genomic features of these phages indicate that natural phages are capable of lysing pathogenic E.coli and have great potential in the biocontrol of bacteria.


Comparing the BDI-II and the PHQ-9 with outpatient substance abusers.
Because of the high co-occurrence of Axis-I mood disorders with primary substance use disorders (SUD), it is important to routinely assess substance abusers for evidence of a mood disorder. The primary goal of the present study was to examine the psychometric characteristics of two widely used self-report measures of depression (Beck Depression Inventory-II; Patient Health Questionnaire PRIME MD) with substance abusers (N=108) in an outpatient treatment setting. Using Cronbach's alpha, the reliabilities of the BDI-II and the PHQ-9 were 0.95 and 0.91, respectively. Principal component factor analyses of both measures were conducted to evaluate the relationship between a 3-factor solution (cognitive, affective, and somatic) for the BDI-II and a 1-factor solution for the PHQ-9 (depression). Both measures were correlated with severity levels of alcohol and drug use. Advantages and disadvantages of using both measures with substance abusers are discussed.


Internal thoracic artery patch repair of a saccular left main coronary artery aneurysm.
A saccular aneurysm located at the bifurcation of the left main coronary artery (LMCA) is an extremely rare condition. A major cause of left main coronary aneurysm is atherosclerosis, and common complications include thrombosis, embolism, and rupture. Despite the serious nature of this condition, the ideal operative approach to LMCA aneurysm (LMCAA) has not been established. Furthermore, little is known about resection of the saccular aneurysm and closure using a small internal thoracic artery patch. Here, we present the case of a 66-year-old woman who had significant stenosis in the left anterior descending artery and a saccular aneurysm at the bifurcation of the LMCAA, which was repaired using a small internal thoracic artery patch during coronary artery bypass grafting. Postoperative multislice computed tomography revealed the complete disappearance of the aneurysm and a successful repair with no luminal stenosis of the internal thoracic artery patch. In addition, the left internal thoracic artery graft was found to be patent. Resection of the saccular LMCA aneurysm and closure using a small internal thoracic artery patch is safe and offer excellent results.


Achieving PN through the selective recovery of AOB activity in inactivated nitrifying bacteria: Combined aerobic starvation and FA.
A novel strategy combining aerobic starvation and free ammonia (FA) was proposed to achieve partial nitrification (PN). The impact of the combined strategy on nitrifying bacteria was explored in a 200-day experiment. The effluent concentration of ammonia was below the detection limits (0.1 mg/L), and the effluent concentration of nitrite and nitrate was 68.12 mg/L and 3.46 mg/L without adding carbon source to the artificial wastewater. The nitrite accumulation rate (NAR) was maintained at 90.15% even when the dissolved oxygen (DO) concentration was 1.50 mg/L. Further analysis showed that PN was achieved by selectively restoring the activity of ammonia-oxidizing bacteria (AOB) in nitrifying bacteria that had lost their activity after starvation. The specific ammonia oxidation rate (SAOR) was 46.25 mg N/g MLVSS/h, and the specific nitrate product rate (SNPR) was only 0.73 mg N/g MLVSS/h in the stable operation stage. The increase in AOB abundance (from 2.79% to 7.13%) and the decrease in nitrite-oxidizing bacteria (NOB) abundance (from 8.75% to 1.44%) explained this phenomenon. Finally, the analyses on the secretion of extracellular polymer substance (EPS), strategies to resist harsh environments, and physical properties of sludge explored the potential mechanism and provided references for applying the combined strategy.


Enhancing Data Security of Cloud Based LMS.
Around the world, the educational system is evolving. The new trend can be found in traditional classroom systems as well as digitalization systems. Cloud-based Learning Management Systems (LMS) will accelerate the educational industry forward in the next years because they can provide end-user with a versatile, convenient, secure, and cost-effective learning process. The cloud-based LMS approach is the most effective and proper learning model in the worldwide educational sector, particularly if the organization is in a state of depression owing to a global pandemic. It can be utilized over the internet with several users on the same platform. As a result, the initial requirement is important to enable to the LMS model. Despite its many advantages, LMS confronts challenges such as confidentiality, user acceptance, and traffic. In a pandemic like Covid 19, the entire planet depends on a safe LMS platform to establish student and instructor trust. Therefore, with this work, the attempt has been made to explain one LMS model that may provide its users with optimal security, a user-friendly environment, and quick access. This paper discusses the use of the cloud attack, and also cryptographic and steganographic security models and techniques to address these issues. There's also information on what kinds of security vulnerabilities or operations on cloud data are feasible, and also how to deal with them using various algorithms.


Targeting HNRNPM Inhibits Cancer Stemness and Enhances Antitumor Immunity in Wnt-activated Hepatocellular Carcinoma.
Cancer stemness and immune evasion are closely associated and play critical roles in tumor development and resistance to immunotherapy. However, little is known about the underlying molecular mechanisms that coordinate this association. The expressions of heterogeneous nuclear ribonucleoprotein M (HNRNPM) in 240 hepatocellular carcinoma (HCC) samples, public databases, and liver development databases were analyzed. Chromatin immunoprecipitation assays were performed to explore the associations between stem-cell transcription factors and HNRNPM. HNRNPM-regulated alternative splicing (AS) and its binding motif were identified by RNA-seq and RIP-seq. HNRNPM-specific antisense oligonucleotides were developed to explore potential therapeutic targets in HCC. CD8+ T cells that were co-cultured with tumor cells were sorted by flow cytometry assays. We identified an elevated oncofetal splicing factor in HCC, HNRNPM, that unifies and regulates the positive association between cancer stemness and immune evasion. HNRNPM knockdown abolished HCC tumorigenesis and diminished cancer stem cell properties in vitro and in vivo. Mechanistically, HNRNPM regulated the AS of MBD2 by binding its flanking introns, whose isoforms played opposing roles. Although MBD2a and MBD2c competitively bound to CpG islands in the FZD3 promoter, MBD2a preferentially increased FZD3 expression and then activated the WNT/β-catenin pathway. Interestingly, FZD3 and β-catenin further provided additional regulation by targeting OCT4 and SOX2. We found that HNRNPM inhibition significantly promoted CD8+ T cell activation and that HNRNPM- antisense oligonucleotides effectively inhibited WNT/β-catenin to enhance anti-programmed cell death protein-1 immunotherapy by promoting CD8+ T cell infiltration. HNRNPM has a tumor-intrinsic function in generating an immunosuppressive HCC environment through an AS-dependent mechanism and demonstrates proof of the concept of targeting HNRNPM in tailoring HCC immunotherapeutic approaches.


Fluid consumption in water-deprived rats after administration of naloxone or quaternary naloxone.
Water-deprived male rats were given access to water, or to a 0.005M sodium saccharin solution, or to a 0.9% sodium chloride solution, during a 30 min test period. Naloxone (0.01-10.0 mg/kg) produced dose-dependent reductions in the consumption of each fluid. Saccharin-drinking was significantly reduced by 0.01 mg/kg naloxone, and water- and saline-drinking by 0.1 mg/kg naloxone. Quaternary naloxone (0.01-10.0 mg/kg) had no effect on drinking under any condition. Access to the saline solution resulted in hyperdipsia, due to a prolongation of the initial bout of avid drinking in the thirsty rats. Naloxone, in small doses, completely abolished this hyperdipsia. Since the quaternary compound had no effect, it was concluded that opiate antagonist suppression of saline-induced hyperdipsia was probably mediated at central opiate receptors.


Outcome of the unaffected contralateral hip in unilateral slipped capital femoral epiphysis: a report comparing prophylactic fixation with observation.
This was a retrospective review of 80 patients with unilateral slipped capital femoral epiphysis treated with either prophylactic fixation or observation. The unaffected hip of 44 patients (mean age 12.6 years) were subjected to simultaneous prophylactic fixation and 36 patients (mean age 13.4 years) were managed by observation. Fisher's exact test showed a significantly high incidence of sequential slip of unaffected hips in the observation group in comparison with prophylactic fixation (P=0.002). No cases had avascular necrosis or chondrolysis. Prophylactic fixation significantly reduces the incidence of sequential slip. It outweighs the minimal surgical risks compared with its benefit in the prevention of further sequential slip.


Rare male advantage and sex ratio.
Relative success of mutant white and wild-type CS Drosophila melanogaster males is frequency-dependent, if sex ratio is 1:1. If the number of females is constant, this success depends on the ratio between the mutant and wild-type males. The sex ratio changes strongly affect the male mating activity of both genotypes. Emphasis is placed on the general interest of the Ayala equation and the Wattiaux-Lichtenberger equation in frequency-dependence and sex ratio dependence analysis.


Synthesis and Characterization of Coordinatively Unsaturated Copper (II) Complexes of 1,3-Bis(2'-Pyridyl)-1,2-Diaza-2-Butene and Their Antityrosinase Activity.
The coordinatively unsaturated copper (II) complexes of 1,3-bis(2'-pyridyl)-1,2-diaza-2- butene with different ancillary anions were synthesized which can bind to copper centers of tyrosinase enzyme. The compounds were found to exhibit inhibitory activities against mushroom tyrosinase and the nature and extent of inhibition is modulated according to the type of ancillary anions.


Vaginal Birth at Term - Part 2. Guideline of the DGGG, OEGGG and SGGG (S3-Level, AWMF Registry No. 015/083, December 2020).
Purpose This guideline aims to summarize the current state of knowledge about vaginal birth at term. The guideline focuses on definitions of the physiological stages of labor as well as differentiating between various pathological developments and conditions. It also assesses the need for intervention and the options to avoid interventions. The second part of this guideline presents recommendations and statements on care during the dilation and expulsion stages as well as during the placental/postnatal stage. Methods The German recommendations largely reproduce the recommendations of the National Institute for Health and Care Excellence (NICE) CG190 guideline "Intrapartum care for healthy women and babies". Other international guidelines were also consulted in individual cases when compiling this guideline. In addition, a systematic search and analysis of the literature was carried out using PICO questions where necessary, and other systematic reviews and individual studies were taken into account. For easier comprehension, the assessment tools of the Scottish Intercollegiate Guidelines Network (SIGN) were used to evaluate the quality of additionally consulted studies. Otherwise, the GRADE system was used for the NICE guideline, and the evidence reports of the IQWiG were used to evaluate the quality of the evidence. Recommendations Recommendations and statements were formulated based on identified evidence and/or a structured consensus.


Cytotoxicity of ester and ether lysophospholipids on Leishmania donovani promastigotes.
The cytotoxic activity of four ester lysophospholipids, three ether lysophospholipids, and two radylglycerols on Leishmania donovani promastigotes was determined by measuring the inhibition of cell growth. The 1-acyl lysophospholipids reduced cell growth to 50% of controls at concentrations of 6.4-10.9 microM. In contrast, 1-O-alkenyl-sn-glycero-3-phosphoethanolamine, 1-O-hexadecyl-sn-glycero-3-phosphocholine, and 1-O-hexadecyl-sn-glycerol already showed a 50% inhibition of growth at concentrations between 2.1 and 2.8 microM. Moreover, the unnatural alkyl lysophospholipid analogue 1-O-octadecyl-2-methoxy-sn-glycero-3-phosphocholine was even 10-fold more toxic. Incubations of L. donovani promastigotes with radioactively labelled ether lysophospholipids revealed a rapid uptake of these compounds and their incorporation into cellular lipids at a non-toxic concentration of 1.0 microM. An accumulation of the lysophospholipids in the cell due to insufficient metabolism may be the cause of its cytotoxic effect. The sensitivity of L. donovani cells towards ether lysophospholipids was found to be similar to that reported for tumor cells.


Hierarchical self-assembly of DNA into symmetric supramolecular polyhedra.
DNA is renowned for its double helix structure and the base pairing that enables the recognition and highly selective binding of complementary DNA strands. These features, and the ability to create DNA strands with any desired sequence of bases, have led to the use of DNA rationally to design various nanostructures and even execute molecular computations. Of the wide range of self-assembled DNA nanostructures reported, most are one- or two-dimensional. Examples of three-dimensional DNA structures include cubes, truncated octahedra, octohedra and tetrahedra, which are all comprised of many different DNA strands with unique sequences. When aiming for large structures, the need to synthesize large numbers (hundreds) of unique DNA strands poses a challenging design problem. Here, we demonstrate a simple solution to this problem: the design of basic DNA building units in such a way that many copies of identical units assemble into larger three-dimensional structures. We test this hierarchical self-assembly concept with DNA molecules that form three-point-star motifs, or tiles. By controlling the flexibility and concentration of the tiles, the one-pot assembly yields tetrahedra, dodecahedra or buckyballs that are tens of nanometres in size and comprised of four, twenty or sixty individual tiles, respectively. We expect that our assembly strategy can be adapted to allow the fabrication of a range of relatively complex three-dimensional structures.


Partial correction of chromosome instability in Fanconi anemia by desferrioxamine.
The action of the iron chelator desferrioxamine (DFO) on the cytogenetic pattern of cultured lymphocytes from Fanconi anemia (FA) patients was investigated. The addition of 10(-4) M DFO throughout the culture time resulted in a 50% reduction of the spontaneous chromosome breakage of FA cells. In addition, the clastogenic action of diepoxybutane on FA lymphocytes was also partly counteracted by DFO. The above findings support the assumption that one of the mechanisms involved in the pathogenesis of FA might be an impaired capacity of the cells from such patients to remove active oxygen species. The relationship between intraleukocyte chelatable iron pool and free radical formation in FA subjects is discussed.


Lectin-based assay for the determination of the inhibition activity of small molecule inhibitors of neuraminidases.
Small molecules inhibitors of neuraminidases (NAs) are ones of the most prospective molecules proposed for the treatment of influenza viruses. The determination of their inhibition activity in vitro is an important step during the development of antiviral drugs. However, the analytical methods typically used for the evaluation of NA activity and inhibition (fluorescence-based assays using MUNANA substrate or thiobarbituric acid assay, TBA) may suffer from interferences caused by tested inhibitors as signal quenching or self-fluorescence, moreover in TBA are used toxic and carcinogenic reagents. The determination of the NA activity can be effectively performed by alternative methods based on lectin - glycan recognition, usually as enzyme-linked lectin assay (ELLA). We have adapted the ELLA assay to a lectin-based assay in a microplate format with fluorescence detection for determination of NA inhibitory activity. We optimized our protocol and the developed method was tested using four different small molecule NA inhibitors or potential NA inhibitors (DANA, zanamivir, quercetin and α-mangostin) with three bacterial NAs (from Clostridium perfringens, Vibrio cholerae and Arthrobacter ureafaciens), and the IC50 values for NA inhibitors were determined. The inhibition effect of DANA was observed for all 3 tested NAs (IC50 = 10.1 μM for V. cholerae, 13.4 μM for C. perfringens and 402.9 μM for A. ureafaciens, respectively) and of Zanamivir only for NA from V. cholerae (IC50 = 101.9 μM). For both quercetin and α-mangostin, no inhibition effect to the tested NAs was observed. The main advantages of herein described method are good sensitivity due to fluorescent signal detection, the absence of the interference caused by fluorescent signal quenching by tested inhibitors, the use of natural substrates (glycoproteins) and the avoiding the use of toxic reagents.


Substituent effects on the PMR signals of methyl groups in methyl steroids.
Proton magnetic resonance (PMR) signals were assigned to each of the methyl groups for a variety of C-3 oxygenated 4-monomethyl, 6-monomethyl, 4, 4-dimethyl, and 2, 2-dimethyl steroids related to 5alpha-cholestane series. The effects of various substituents (i.e. methyls at C-4, C-6, or C-2, functional groups at C-3, and unsaturated bonds) on the methyl proton resonances have been derived from the assignment. The application of such data to structural and stereochemical problems has also been discussed.


Inhibition of human neuroblastoma cell proliferation and EGF receptor phosphorylation by gangliosides GM1, GM3, GD1A and GT1B.
The inhibitory action of gangliosides GT1B, GD1A, GM3 and GM1 on cell proliferation and epidermal growth factor receptor (EGFR) phosphorylation was determined in the N-myc amplified human neuroblastoma cell line NBL-W. The IC50 of each ganglioside was estimated from concentration-response regressions generated by incubating NBL-W cells with incremental concentrations (5-1000 microm) of GT1B, GD1A, GM3 or GM1 for 4 days. Cell proliferation was quantitatively determined by a colourimetric assay using tetrazolium dye and spectrophotometric analysis, and EGFR phosphorylation by densitometry of Western blots. All gangliosides assayed, with the exception of GM1, inhibited NBL-W cell proliferation in a concentration-dependent manner. The IC50s for gangliosides GT1B [molecular weight (MW) 2129], GM3 (MW 1236), and GD1A (MW 1838) were (mean +/- SEM) 117 +/- 26, 255 +/- 29, and 425 +/- 44 m, respectively. In contrast, the IC50 for GM1 (MW 1547) could not be determined. Incubation of NBL-W cells with epidermal growth factor (EGF) concentrations ranging from 0.1 to 1000 ng/ml progressively increased cell proliferation rate, but it plateaued at concentrations above 10 ng/ml. EGFR tyrosine phosphorylation, however, was incrementally stimulated by EGF concentrations from 1 to 100 ng/ml. The suppression of EGF-induced EGFR phosphorylation differed for each ganglioside, and their respective inhibitory potencies were as follows: EGFR phosphorylation [area under curve (+ EGF)/area under curve (- EGF)]: control (no ganglioside added) = 8.2; GM1 = 8.3; GD1A = 6.7; GM3 = 4.87, and GT1B = 4.09. The lower the ratio, the greater the inhibitory activity of the ganglioside. Gangliosides GD1A and GT1B, which have terminal N-acetyl neuraminic acid moieties, as well as one and two N-acetyl neuraminic acid residues linked to the internal galactose, respectively, both inhibited cell proliferation and EGFR phosphorylation. However, GD1A was a more potent suppressor of cell proliferation and GT1B most effective against EGFR phosphorylation. GM3, which only has a terminal N-acetyl neuraminic acid, inhibited cell proliferation and EGFR phosphorylation almost equivalently. These data suggest that gangliosides differ in their potency as inhibitors of NBL-W neuroblastoma cell proliferation and EGFR tyrosine phosphorylation, and that perturbations in the differential expression of membrane glycosphingolipids may play a role in modulating neuroblastoma growth.


Defining aims for a veterinary school.
The Faculty of Veterinary Science at the University of Queensland has defined the aims of the Veterinary School for the future. The aims are to foster excellence in teaching, research, and other forms of professional activity in veterinary science. These aims are being used as a basis for future planning within the School.


Effects of electro-acupuncture at Tongli (HT 5) and Xuanzhong (GB 39) acupoints from functional magnetic resonance imaging evidence.
To explore the specifificity of Tongli (HT 5) and Xuanzhong (GB 39) paired acupionts in aspects of Deqi sensation and brain activation patterns during electroacupuncture. In this study, 15 healthy subjects were enrolled. All participants suffered two kinds of functional magnetic resonance imaging (fMRI) examinations randomly: Examination A received electro-acupuncture (EA) at the bilateral Tongli (HT5) and Xuanzhong (GB 39) acupoints (ACU), and examination B received EA at bilateral non-acupoints (NAP). The subjects reported the feeling of Deqi at each examination later respectively. A multi-voxel pattern analysis method and Statistical Program for Social Sciences were used to analyze the data. The ACU group (Exam A) reported fullness, heaviness, numbness, soreness and throbbing of signifificantly greater intensity than the NAP group (Exam B). In addition, there was no statistical signifificance between two groups in aching, tingling, deep pressure, sharp pain, dull pain, warmness and cold. Meanwhile, fMRI data revealed differences between two groups in discriminating accuracy of brain somatosensory cortex and language-related cortices. Needling HT 5 and GB 39 may modulate language function through a complex brain network, suggesting that it may be benefificial to the recovery of language function in patients with aphasia.


Multiple splenic infarcts in acute Plasmodium vivax malaria: a rare case report.
In tropical countries like India, malaria has been one of the most common parasitic illnesses leading to frequent hospitalization and causing major economic burden among the masses. Although Plasmodium vivax infection is considered to be benign, in contrast to Plasmodium falciparum infection which is notorious for its severe splenic complications can occur frequently. Splenomegaly tends not to receive special attention, as it is not usually accompanied by any symptoms and can be gradually resolved via standard antimalarial therapy. Splenic infarction, although rarely attributable to malaria in an endemic region with high parasitemia, can be a rare presentation of this disease entity.


Effect of spacer alkyl chain length on retention among three imidazolium stationary phases under various modes in high performance liquid chromatography.
The properties of ionic liquids (ILs) greatly influenced the retention of solutes on IL-functionalized stationary phases. In this work, three IL-functionalized stationary phases (Sil-C4Im, Sil-C7Im, and Sil-C10Im) were prepared by modifying silica gel with three ionic liquid silane reagents differing in spacer alkyl chain lengths, which refers to the alkyl chain between the imidazolium and the sulfur atom. The preparation was proved through a range of characterization techniques, including elemental analysis (EA), Fourier transform infrared spectroscopy (FT-IR), and thermogravimetric analysis (TGA). The effects of chromatographic conditions, such as acetonitrile content, salt concentration, pH, and column temperature, were studied to explore the retention mechanism of three stationary phases, which indicates that three IL-stationary phases provide interactions with solutes in reverse-phase liquid chromatography (RPLC), hydrophilic interaction liquid chromatography (HILIC), and ion exchange chromatography (IEC). The column efficiency is 83,686 plates/m for aminobenzoic acid, and the column also has excellent repeatability of retention time with relative standard deviations (RSDs) between 0.24% and 0.34% (n = 12). A variety of analytes, including five nucleosides and nucleobases, six alkylbenzenes, two polycyclic aromatic hydrocarbons (PAHs), and four inorganic anions, were separated well on three IL-functionalized stationary phases. It was found that the spacer alkyl chain length influenced selectivity by comparing the retention of the three IL-functionalized stationary phases.


Beta-interferon therapy in patients with poor-prognosis Kaposi sarcoma related to the acquired immunodeficiency syndrome (AIDS). A phase II trial with preliminary evidence of antiviral activity and low incidence of opportunistic infections.
To study the efficacy of high doses of beta-ser-interferon (recombinant human 17-serine beta-interferon) in patients with human immunodeficiency virus (HIV) infection and Kaposi sarcoma. A nonrandomized, controlled trial of two high-dose regimens of beta-ser-interferon administered until tumor progression, toxicity, or an acquired immunodeficiency syndrome (AIDS)-defining opportunistic infection occurred. An AIDS treatment clinic at a tertiary care center. A sequential sample of 39 patients with biopsy-proven, AIDS-related Kaposi sarcoma were enrolled during a 2-year period. Thirty-eight patients were evaluable for response. Most patients (35 of 38) had one or more of the following clinical or laboratory predictors for a poor response to interferon therapy: HIV p24 antigenemia, low CD4 cell numbers, elevated beta 2-microglobulin levels, previous opportunistic infections, or previous systemic chemotherapy. Beta-ser-interferon was self-administered subcutaneously at home 5 days per week. The first 21 patients used 90 million IU/d, and the remainder used 180 million IU/d. Six patients (16%) had a major clinical response, and 15 (39%) had stable disease for prolonged periods. Toxicities were minimal; the major toxicity was a skin reaction at the injection site. The HIV p24 antigen level declined more than 50% in 8 of the 19 patients with initial values greater than 50 pg/mL. Antiretroviral activity and antitumor activity were seen only in patients with normal initial beta 2-microglobulin levels. Minimal changes were seen in CD4 and CD8 cell numbers. Only 1 patient had an opportunistic infection while on study, but five other patients developed infections after treatment was discontinued for an incidence of six opportunistic infections in 285 patient-observation months. The high doses of interferon did not improve the major response rate in patients with poor-prognosis, AIDS-related Kaposi sarcoma. There was, however, a suggestion of antiviral activity in patients with normal beta 2-microglobulin levels and a decrease in the expected incidence of opportunistic infections.


Bioactivity of polysaccharides derived from bivalves.
Bivalves have high diversity, widely distributed in various aquatic environments, including saltwater, brackish water and freshwater. Bivalves are known to rich in polysaccharides and have wide applications in functional foods, pharmaceuticals, and industrial research. Despite many relevant reports are available, the information is poorly organized. Therefore, in this study, we conducted a comprehensive scientific review on the potential bioactivity of polysaccharides derived from bivalves. In general, the polysaccharides derived from bivalves possess various bioactive properties, including anticancer, antioxidant, anticoagulant and immunomodulatory activities. The bioactivity of these biomolecules highly depends on the bivalve species, extraction methods, purification methods, dosages, etc. The information in this study can provide an overview of the bioactivities of bivalve polysaccharides. This is very useful to be used as a guide for identifying the health benefits of polysaccharides derived from different bivalve species.


Estimating Sepsis Incidence Using Administrative Data and Clinical Medical Record Review.
Despite the large health burden, reliable data on sepsis epidemiology are lacking; studies using International Statistical Classification of Diseases and Related Health Problems (ICD)-coded hospital discharge diagnosis for sepsis identification suffer from limited sensitivity. Also, ICD data do not allow investigation of underlying pathogens and antimicrobial resistance. To generate reliable epidemiological estimates by linking data from a population-based database to a reference standard of clinical medical record review. This was a retrospective, observational cohort study using a population-based administrative database including all acute care hospitals of the Scania region in Sweden in 2019 and 2020 to identify hospital-treated sepsis cases by ICD codes. From this database, clinical medical records were also selected for review within 6 strata defined by ICD discharge diagnosis (both with and without sepsis diagnosis). Data were analyzed from April to October 2022. Hospital and population incidences of sepsis, case fatality, antimicrobial resistance, and temporal dynamics due to COVID-19 were assessed, as well as validity of ICD-10 case identification methods compared with the reference standard of clinical medical record review. Out of 295 531 hospitalizations in 2019 in the Scania region of Sweden, 997 patient medical records were reviewed, among which 457 had sepsis according to clinical criteria. Of the patients with clinical sepsis, 232 (51%) were female, and 357 (78%) had at least 1 comorbidity. The median (IQR) age of the cohort was 76 (67-85) years. The incidence of sepsis in hospitalized patients according to the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) criteria in 2019 was 4.1% (95% CI, 3.6-4.5) by medical record review. This corresponds to an annual incidence rate of 747 (95% CI, 663-832) patients with sepsis per 100 000 population. No significant increase in sepsis during the COVID-19 pandemic nor a decrease in sepsis incidence when excluding COVID-19 sepsis was observed. Few sepsis cases caused by pathogens with antimicrobial resistance were found. The validity of ICD-10-based case identification in administrative data was low. In this cohort study of sepsis epidemiology, sepsis was a considerable burden to public health in Sweden. Supplying administrative data with information from clinical medical records can help to generate reliable data on sepsis epidemiology.


[Acute management of spontaneous intracerebral hemorrhage].
Intracerebral hemorrhage accounts for approximately 15% of the 115,000 strokes occurring each year in France. Although therapeutic strategies are more limited than for ischemic stroke, major points in the management of intracerebral hemorrhage can reduce short term morbidity and mortality by limiting the expansion of the hematoma and the occurrence of early complications, and long term patients' outcome by reducing the risk of recurrence. This article aims to update the key elements that contribute to improve of the prognosis of intracerebral hemorrhage patients.


Comparative analysis of the growth and development differences of children and adolescents between developed and undeveloped urban and rural areas in China.
Our study use the height and weight data of Chinese students aged 7-18 years from 1985 to 2014 to investigate the inequality and changing trend of height and weight of children and adolescents in different regions. Our study extracted data from the 1985, 2000, and 2014 Chinese National Survey on Students' Constitution and Health (CNSSCH) for a comparative analysis of the height and weight of children and adolescents aged 7-18 years in a developed city (Shanghai) and an underdeveloped province (Guizhou). The coefficients of variation (CVs) of height and weight between urban and rural boys and girls were also calculated. Since 1985, the height difference between urban and rural areas has decreased from 4.24 to 2.41 cm for boys and 3.72 to 1.99 cm for girls. The weight difference for boys and girls increased from 1.83 to 3.10 kg and from 0.97 to 1.80 kg, respectively. However, from 1985 to 2014, the height and weight differences between Shanghai and Guizhou increased. In addition, from 1985 to 2014, the coefficient of height variation was greater for rural students than urban students while the coefficient of weight variation was greater for urban students than rural students. Although the difference between urban and rural areas has recently decreased, the difference between developed area (Shanghai) and underdeveloped area (Guizhou) has increased. In particular, the difference in height and weight between children in developed areas (Shanghai) and non-developed areas (Guizhou) has become larger since 1985-2014, rather than gradually decreasing over time.


Surveillance, prevention and control of hospital-acquired infections. III. Nosocomial infections as cause of death: retrospective analysis of 1000 autopsy reports.
One thousand post-mortem reports were analysed retrospectively to see whether the patient had had a nosocomial or community-acquired infection and whether this led directly to or contributed to the patient's death. In 7.4% of all autopsies nosocomial infection was the direct cause of death. In 6.3% of the patients, nosocomial infection was a contributory factor leading to death. The most common hospital infections were pneumonia, septicaemia, peritonitis, meningitis, and hepatitis B. Most infections which led to or contributed to death were acquired in surgical wards. Patients with nosocomial infections, however, were more endangered by factors predisposing to infections (1.8 factors per patient) than patients without nosocomial infections (0.67 factors per patient). Sixty-three patients acquired an infection outside the hospital; in 70% of these patients, the infection was the main or contributory cause of death.


Ecological studies on chironomids in Lake Suwa : I. Population dynamics of two large chironomids, Chironomus plumosus L. and Spaniotoma akamusi Tokunaga.
Population dynamics of two large chironomids, Chironomus plumosus and Spaniotoma akamusi in Lake Suwa were studied through a four-year period from 1967 to 1970. 1. Based on the daily catches of midge by means of light trap, three emergence periods in a year were confirmed in C. plumosus (April-May, June-July and August-October) and only one in S. akamusi (October-November). 2. C. plumosus produces three generations yearly in the littoral region. In the profundal region, however, it usually lacks the second generation and some part of the larvae of the first generation emerges finally in the third emergence period. 3. Larvae of S. akamusi disappeared from the surface layer of mud bottom in May as the result of their burrowing. Pupation and emergence took place after their reppearance at the surface layer in September. 4. In the imagines of C. plumosus trapped through an emergence period, males as a rule predominated over females (males 50-83%). The predominance of males over females was even more striking expressed in S. akamusi (males 83-93%). 5. Population density of larvae of C. plumosus attained its maximum in June (ca. 1200-5400 individuals/m2 in the profundal region) and in October (ca. 1500 to 2100/m2 in the same region) with the appearance of newly hatched larvae in the lake bottom. The maximum of biomass appeared either in correspondence to that of population density or a little later, and reached 15-90 and 10-27 g fresh weight/m2 in the above-mentioned periods respectively. 6. Population density of larvae of S. akamusi reached a maximum (ca. 700 to 4800 individuals/m2 in the profundal region) in the period from December to March. The maximum biomass was found in March (ca. 10-96 g fresh wt./m2) when the growth of the larvae had been almost completed. 7. Survival rate of wintered larvae of C. plumosus was very low (ca. 6-7%) in 1968 and 1969, whereas it amounted to about 70% in 1970, followed by an unusually intensive emergence. 8. The quantity of pupae produced in an emergence period was estimated based on the numbers of larvae before and after emergence. The total amount of pupae produced per year was estimated at ca. 268-354 tons in C. plumosus and at ca. 10-168 tons in S. akamusi for the whole lake. A certain quantitative relationship was found between the total number of trapped imagines and the estimated number of pupae produced in an emergence period in both species.


Bradycardia and hypotension refractory to ephedrine and atropine treatment: severe autonomic dysfunction with abnormal heart rate variability.
Diabetic patients with autonomic dysfunction are potentially poor risks for anesthesia and particular care is needed during and after surgery. We here report a 48-year-old male patient with diabetes mellitus who suffered from intraoperative hypotension and bradycardia which did not respond to ephedrine and atropine treatment and eventuated in cardiac arrest. A heart rate variability study confirmed the diagnosis of autonomic dysfunction after the event. Possible predisposing mechanisms and anesthetic considerations are discussed.


[Surgical treatment of a complication of Crohn's disease of the duodenum].
In 1995-1997 at the First Surgical Clinic, Medical Faculty, Palacký University and Faculty Hospital Olomouc three patients were treated on account of obstruction of the pyloroduodenal region caused by Crohn's disease. The condition was treated by anastomosis, possibly with vagotomy, depending on the site of stenosis. Clinical, laboratory and endoscopic control examinations after a 6-month to 3-year interval revealed good results of this approach.


Relative receptor expression is a determinant in xenobiotic-mediated CYP3A induction in rat and human cells.
1. Species differences in xenobiotic-mediated transcriptional activation of CYP3A genes are known to exist. These differences are proposed to be due, in part, to host cell differences. 2. Host cell effects were investigated by trans-species transient transfection of reporter genes containing either the rat CYP3A23 or human CYP3A4 proximal promoters into human HepG2 and rat FaO and H4IIEC3 hepatoma cells. HepG2 and FaO cells supported activation of both CYP3A constructs by xenobiotics in a species-specific manner, whereas H4IIEC3 cells were non-permissive. 3. The mRNA complement of the cell lines was then quantified by semiquantitative RT-PCR for adult CYP3As (CYP3A23, CYP3A4/5), steroid hormone receptors (constitutive androstane receptor, glucocorticoid receptor-alpha, pregnane X receptor) and transcription factors (Hepatic nuclear factor 4alpha, retinoid X receptor). 4. Principal component analysis of absolute receptor levels demonstrated a wide scattering, with no coherent pattern. In contrast, PCA of relative receptor ratios segregated H4IIEC3 cells from all other samples. 5. The observation is confirmed that species differences in response to xenobiotics are a result of host cell environment. In addition, new evidence is provided to support the hypothesis that in addition to individual receptor activation profiles, the relative abundance of steroid hormone receptors that control CYP3A gene expression play an important role in this observed species difference.


Glucosyl transferase activity of bovine galactosyl transferase.
Bovine galactosyl transferase was found to utilize UDPglucose as a substrate and elicit disaccharide biosynthesis with glucose and N-acetylglucosamine as acceptors. The relative rate of glucosyl transferase with N-acetylglucosamine as acceptor was 0.3%, the rate for N-acetyllactosamine biosynthesis. This activity was also evidenced indirectly from NMR water proton relaxation experiments, and from Mn(II) ESR experiments. In direct experiments with radioactive UDPglucose, paper chromatography showed a product which migrated with cellobiose when glucose was the acceptor and a new, glucose-containing product which resulted when GlcNAc was the acceptor. Despite this marginally expanded specificity of the donor site, spin-label experiments with a covalently bound UDPgalactose analog reaffirmed the restrictive nature of the donor site against this non-glycosyl-like analog.