Toll-like receptors 2 and 4 exert opposite effects on the contractile response induced by serotonin in mouse colon: role of serotonin receptors.
What is the central question of this study? The action of Toll-like receptors (TLRs) 2 and 4 on the motor response to serotonin in mouse colon has not previously been reported. What is the main finding and its importance? Toll-like receptors 2 and 4 modulate the serotonin-induced contractile response in mouse colon by modifying the expression of serotonin (5-HT) receptors. Alterations in 5-HT2A and 5-HT2C receptors explain the increase of the response to serotonin in TLR2(-/-) mice. Alterations in 5-HT2C and 5-HT4 receptors explain the suppression of the response to serotonin in TLR4(-/-) mice. The microbiota, through Toll-like receptors (TLRs), may regulate gastrointestinal motility by activating neuroendocrine mechanisms. We evaluated the influence of TLR2 and TLR4 in spontaneous contractions and in the serotonin (5-HT)-induced motor response in mouse colon, and assessed the 5-HT receptors involved. Muscle contractility studies to evaluate the intestinal spontaneous motility and the response to 5-HT were performed in the colon from wild-type (WT), TLR2(-/-) , TLR4(-/-) and TLR2/4 double knockout (DKO) mice. The 5-HT receptor mRNA expression was determined by real-time PCR. The amplitude and frequency of the spontaneous contractions of the colon were smaller in TLR4(-/-) and TLR2/4 DKO mice with respect to WT mice. In WT, TLR2(-/-) and TLR2/4 DKO mice, 100 μm 5-HT evoked a contractile response. The contractile response induced by 5-HT was significantly higher in TLR2(-/-) than in WT mice. In TLR4(-/-) mice, 5-HT did not evoke any contractile response. The mRNA expression of 5-HT2A was increased in TLR2(-/-) and TLR2/4 DKO mice. The 5-HT2C and 5-HT4 mRNA expressions were increased in TLR4(-/-) and TLR2/4 DKO mice. The 5-HT2C mRNA expression was diminished in TLR2(-/-) mice. The 5-HT3 mRNA expression was increased in TLR2(-/-) , TLR4(-/-) and TLR2/4 DKO mice. The 5-HT7 mRNA expression was diminished in TLR2/4 DKO mice. In WT, TLR2(-/-) and TLR2/4 DKO mice, 5-HT2 , 5-HT3 , 5-HT4 and 5-HT7 receptor antagonists reduced or blocked the contractile response evoked by 5-HT. We postulate that TLR2 and TLR4 modulate the serotonin contractile motor response in mouse colon in an opposing manner by modifying the expression of several serotonin receptors.


Improved bioavailability of orally delivered insulin using Eudragit-L30D coated PLGA microparticles.
Large porous microparticles of PLGA entrapping insulin were prepared by solvent evaporation method and evaluated in diabetes induced rat for its efficacy in maintaining blood sugar level from a single oral dose. Incorporation of Eudragit L30D (0.03% w/v) in the external aqueous phase resulted in formation of pH responsive enteric coated polymer particles which release most of the entrapped insulin in alkaline pH. At acidic pH, release of insulin from uncoated PLGA microparticles and Eudragit L30D coated PLGA microparticles was 31.62 +/- 1.8% and 17.5 +/- 1.29%, respectively, for initial 30 min. However, in 24 h, in vitro released insulin from uncoated PLGA and Eudragit coated particles was 96.29 +/- 1.01% and 88.30 +/- 1%, respectively. Released insulin from composite polymer particles were mostly in monomer form without aggregation and was stable for a month at 37 degrees C. Oral administration of insulin loaded PLGA (50 : 50) and Eudragit L30D coated PLGA (50 : 50) microparticles (equivalent to 25 IU insulin/kg of animal weight) in alloxan induced diabetic rats resulted in 37.3 +/- 11% and 62.7 +/- 3.8% reduction in blood glucose level, respectively, in 2 h. This effect continued up to 24 h in the case of Eudragit L30D coated PLGA microparticles. Results demonstrate that use of stabilizers during PLGA particle formulation, large porous particle for quick release of insulin and coating with Eudragit L30D resulted in a novel oral formulation for once a day delivery of insulin.


Protective and pathogenic roles for mast cells during viral infections.
Mast cells (MCs) are long-lived immune cells. They are armed with preformed mediators within granules that can be instantaneously released in response to an invading pathogen, including certain viruses. At the skin and mucosae, they initiate innate immune responses and promote the development of adaptive immune responses, through cellular recruitment or antigen presentation. However, systemic MC activation may promote immune pathologies through their vasoactive proteases and biogenic amines. Recently, MC products were identified to contribute to pathologies associated with viral hemorrhagic fever, such vascular leakage and thrombocytopenia. Similar associations of MCs with disease severity have been noted for certain respiratory viral pathogens. Here we discuss the specific MC responses to viruses and their influences on functional immune outcomes during infection.


Urinary Concentrations of Parabens in a Population of Iranian Adolescent and Their Association with Sociodemographic Indicators.
Parabens are widely used as preservatives in personal care products, foodstuffs, and pharmaceuticals. Concerns have been raised regarding the potential endocrine disruption effects of parabens. In the present study, the urinary concentration of four common parabens, including methylparaben (MP), ethylparaben (EP), propylparaben (PP), and butylparaben (BP), in 100 Iranian adolescents randomly referring to health services centres were analyzed using GC/MS. The association of sociodemographic and lifestyle variables, collected through questionnaire, with the concentration of parabens also were studied. Median concentrations of MP, EP, PP, and BP were 92.21, 8.46, 12.26, and 8.42 µg/g creatinine, respectively. There was a strong positive significant correlation between MP and PP (r = 0.694) and moderate to a weak correlation between the other parabens. The concentration of urinary MP in females was significantly higher than those in male (p = 0.021). There was a significant negative association between different BMI groups and MP and EP. There also was a positive significant association between the MP and age, and between MP, EP, and PP, and tobacco use. Although the estimated daily intake of the parabens was lower than the Acceptable Daily Intake, it was higher than those reported in other countries. This confirms the widespread exposure of Iranian adolescents to the paraben compounds and their association with sociodemographic factors. This was the first study reporting the urinary parabens level in Iranian adolescents, and the data can be used as a basis for assessing the risk of exposure to parabens in the Iranian population in future studies.


Pharmacological targeting of coagulation factor XI attenuates experimental autoimmune encephalomyelitis in mice.
Multiple sclerosis (MS) is the most common causes of non-traumatic disability in young adults worldwide. MS pathophysiologies include the formation of inflammatory lesions, axonal damage and demyelination, and blood brain barrier (BBB) disruption. Coagulation proteins, including factor (F)XII, can serve as important mediators of the adaptive immune response during neuroinflammation. Indeed, plasma FXII levels are increased during relapse in relapsing-remitting MS patients, and previous studies showed that reducing FXII levels was protective in a murine model of MS, experimental autoimmune encephalomyelitis (EAE). Our objective was to determine if pharmacological targeting of FXI, a major substrate of activated FXII (FXIIa), improves neurological function and attenuates CNS damage in the setting of EAE. EAE was induced in male mice using murine myelin oligodendrocyte glycoprotein peptides combined with heat-inactivated Mycobacterium tuberculosis and pertussis toxin. Upon onset of symptoms, mice were treated every other day intravenously with anti-FXI antibody, 14E11, or saline. Disease scores were recorded daily until euthanasia for ex vivo analyses of inflammation. Compared to the vehicle control, 14E11 treatment reduced the clinical severity of EAE and total mononuclear cells, including CD11b+CD45high macrophage/microglia and CD4+ T cell numbers in brain. Following pharmacological targeting of FXI, BBB disruption was reduced, as measured by decreased axonal damage and fibrin(ogen) accumulation in the spinal cord. These data demonstrate that pharmacological inhibition of FXI reduces disease severity, immune cell migration, axonal damage, and BBB disruption in mice with EAE. Thus, therapeutic agents targeting FXI and FXII may provide a useful approach for treating autoimmune and neurologic disorders.


Children's understanding of the causality of pain.
The ideas of 680 Irish schoolchildren aged 5-14 years about the causality of pain were studied as part of a wider investigation of children's understanding of pain. The results indicated an association between pain and 'transgression' consonant with the literature on children's beliefs about the causality of illness, but not reported in previous studies of children's ideas about pain. Developmental patterns were also noted in the data and one significant sex difference consistent with a previously reported trend.


The gastrocolic response: evidence for a neural mechanism.
The aim of this study is to determine the effect of anticholinergic therapy on the gastrocolonic response to a standard meal or its major constituent fat. A rapid increase in rectosigmoidal spike activity occurs after ingesting the standard meal or the fat meal (P less than 0.01). Distal colonic motility returns to fasting levels 50 min after both meals. There is no further increase in spike activity after the 1000-calorie meal, but spike activity increases again 70 min after ingesting the fat (P less than 0.02). The anticholinergic drug, clidinium bromide, inhibits the early increase in spike activity after both meals. However, the anticholinergic has no effect on the delayed peak of activity following the ingestion of fat. This study suggests that (a) the early gastrocolic response to a standard meal and a fat meal is cholinergically mediated and (b) the late increase in rectosigmoidal motility occurs only after fat ingestion and may be controlled by other neural mediators or possibly the gastrointestinal hormones.


The differential diagnosis of bacterial and aseptic meningitis using cerebrospinal fluid laboratory tests.
The lactate, lysozyme, C-reactive protein and serum amyloid-A protein concentrations in cerebrospinal fluid were measured in 11 patients with bacterial meningitis, 27 patients with aseptic meningitis and in 31 control patients. The mean concentration of each parameter was significantly higher (p less than or equal to 0.0001) in patients with bacterial meningitis than in those with aseptic meningitis or those without meningitis. The reliability of these tests in the differential diagnosis of bacterial and aseptic meningitis was compared with leucocyte counts in cerebrospinal fluid. Gram staining for bacteria, and protein and glucose levels. The cerebrospinal fluid lactate level proved to be more sensitive than lysozyme. C-reactive protein or serum amyloid-A protein and had a high degree of specificity.


Sequence elements in both the intergenic space and the 3' untranslated region of the Crithidia fasciculata KAP3 gene are required for cell cycle regulation of KAP3 mRNA.
mRNA levels of several Crithidia fasciculata genes involved in DNA metabolism have previously been found to cycle as cells progress through the cell cycle. Octamer consensus sequences in the 5' untranslated regions (5' UTRs) of these transcripts were shown to be required for cycling of these mRNAs. The KAP3 gene encodes a kinetoplast histone H1-like DNA binding protein, and its mRNA levels cycle in parallel with those of the kinetoplast DNA topoisomerase (TOP2), dihydrofolate reductase-thymidylate synthase (DHFR-TS), and the large subunit of the nuclear single-stranded DNA binding protein (RPA1). KAP3 mRNA contains two octamer consensus sequences in its 3' UTR but none in its 5' UTR. Mutation of these octamer sequences was not sufficient to prevent cycling of a sequence-tagged KAP3 mRNA expressed from a plasmid. Mutation of an octamer sequence contained on the precursor transcript but not on the mRNA, in addition to mutation of the two octamer sequences in the 3' UTR, was necessary to abolish cycling of the mRNA. The requirement for a sequence not present on the mature mRNA indicates that regulation of the mRNA levels by the octamer sequences occurs at or prior to splicing of the transcript. Incompletely processed RNAs containing octamer sequences were also found to accumulate during the cell cycle when the mRNA levels were lowest. These RNA species hybridize to both the KAP3 coding sequence and that of the downstream drug resistance gene, indicating a lack of processing within the intergenic region separating these genes. We propose a cell cycle-dependent interference in transcript processing mediated by octamer consensus sequences as a mechanism contributing to the cycling of such transcripts.


Palytoxin: a potent stimulator of catecholamine release from cultured bovine adrenal chromaffin cells.
The effect of palytoxin (PTX), a potent marine toxin, on catecholamine release from cultured bovine adrenal chromaffin cells was examined. PTX at concentrations of over 10(-9) M induced catecholamine release dose-dependently. About 40-50% of the total cellular catecholamine was released during 20-min incubation with 3 x 10(-8) M PTX. PTX-induced catecholamine release was dependent on both extracellular Na+ and Ca2+, and was inhibited by organic and inorganic Ca2+ channel blockers, but not by tetrodotoxin. PTX-induced increase in 45Ca2+ influx into the cells, which was associated with catecholamine release, was also inhibited by these Ca2+ channel blockers. These results indicated that PTX-induced catecholamine release was mediated by activation of Na(+)-dependent, tetrodotoxin (TTX) insensitive voltage-dependent Ca2+ channels.


Differential polymerization of the two main protein components of dragline silk during fibre spinning.
Spider silks are some of the strongest materials found in nature. Achieving the high tensile strength and elasticity of the dragline of orb-weaving spiders, such as Nephila clavipes, is a principal goal in biomimetics research. The dragline has a composite nature and is predominantly made up by two proteins, the major ampullate spidroins 1 and 2 (refs 3, 6, 7), which can be considered natural block copolymers. On the basis of their molecular structures both spidroins are thought to contribute, in different ways, to the mechanical properties of dragline silk. The spinning process itself is also considered important for determining the observed features by shaping the hierarchical structure of the fibre. Here we study the heterogeneous distribution of proteins along the radial axis of the fibre. This heterogeneity is generated during the conversion of the liquid spinning dope into solid fibre. Whereas spidroin 1 is distributed almost uniformly within the fibre core, spidroin 2 is missing in the periphery and is tightly packed in certain core areas. Our findings suggest that the role of spidroin 2 in the spinning process could be to facilitate the formation of fibrils and contribute directly to the elasticity of the silk.


Statistical information about reward timing is insufficient for promoting optimal persistence decisions.
When deciding how long to keep waiting for delayed rewards that will arrive at an uncertain time, different distributions of possible reward times dictate different optimal strategies for maximizing reward. When reward timing distributions are heavy-tailed (e.g., waiting on hold) there is a point at which waiting is no longer advantageous because the opportunity cost of waiting is too high. Alternatively, when reward timing distributions have more predictable timing (e.g., uniform), it is advantageous to wait as long as necessary for the reward. Although people learn to approximate optimal strategies, little is known about how this learning occurs. One possibility is that people learn a general cognitive representation of the probability distribution that governs reward timing and then infer a strategy from that model of the environment. Another possibility is that they learn an action policy in a way that depends more narrowly on direct task experience, such that general knowledge of the reward timing distribution is insufficient for expressing the optimal strategy. Here, in a series of studies in which participants decided how long to persist for delayed rewards before quitting, we provided participants with information about the reward timing distribution in several ways. Whether the information was provided through counterfactual feedback (Study 1), previous exposure (Studies 2a and 2b), or description (Studies 3a and 3b), it did not obviate the need for direct, feedback-driven learning in a decision context. Therefore, learning when to quit waiting for delayed rewards might depend on task-specific experience, not solely on probabilistic reasoning.


Use of humanized rat basophilic leukemia reporter cell lines as a diagnostic tool for detection of allergen-specific IgE in allergic patients: time for a reappraisal?
The interaction between allergens and specific IgE is at the heart of the allergic response and as such lies at the center of techniques used for diagnosis of allergic sensitization. Although serological tests are available, in vivo tests such as double-blind placebo-controlled food challenges (DBPCFC) and skin prick test (SPT) associated to the patients' clinical history are still the main guides to clinicians in many practices around the world. More recently, complex protein arrays and basophil activation tests, requiring only small amounts of whole blood, have been developed and refined, but are yet to enter clinical practice. Similarly, the use of rat basophilic leukemia (RBL) cell lines for detection of allergen-specific IgE has been made possible by stable transfection of the human FcεRI α chain into this cell line more than 20 years ago, but has not found widespread acceptance among clinicians. Here, we review the perceived limitations of diagnostic applications of humanized RBL systems. Furthermore, we illustrate how the introduction of reporter genes into humanized RBL cells is able to overcome most of these limitations, and has the potential to become a new powerful tool to complement the armamentarium of allergists. A demonstration of the usefulness of humanized RBL reporter systems for elucidation of complex IgE sensitization patterns against wheat proteins and a section on the use of fluorescence-based reporter systems in combination with allergen arrays close the review.


The value of expression of M2-PK and VEGF in patients with advanced gastric cancer.
Glycolytic pyruvate kinase isoenzyme type M2 (M2-PK) plays a key role in tumor metabolism and energy production. Vascular endothelial growth factor (VEGF) is critical in regulating angiogenesis which is an essential process required for tumor growth and metastasis. These two genes may function in accordance with tumor development. The purpose of this study was to investigate the relationship between the expression of M2-PK and VEGF, and their association with clinicopathological features in patients with advanced gastric cancer. Expression of M2-PK and VEGF were examined in 142 cases of paraffin-embedded tissue blocks from patients with advanced gastric cancer. M2-PK expression was found to strongly correlate with that of VEGF (r = 0.718). In addition, expression of M2-PK and VEGF correlates with tumor size (p = 0.0001, and p = 0.0017, respectively), depth of invasion (p = 0.0024, and p = 0.0261, respectively), and lymph node metastasis (p = 0.036, and p = 0.028, respectively). The high expression levels of M2-PK and VEGF may indicate poor prognosis in patients with advanced gastric cancer.


Reflections on the papal allocution concerning care for persistent vegetative state patients.
This article critically examines the recent papal allocution on patients in a persistent vegetative state with regard to the appropriate conditions for considering "reformable statements." In the first part of the article, the purpose and meaning of the allocution are assessed. O'Rourke concludes that give consideration of the individual patient's best interest, prolonging artificial nutrition and hydration is not, in every case, the best option. Although he stresses favorability for preservation of the life of the patient through artificial nutrition and hydration, costs and benefits to the patient should be weighed. Ultimately, he argues in favor of leaving the decision to the patient, his caregivers, and others immediately involved in the case.


Chitosan-transition metal ions complexes for selective arsenic(V) preconcentration.
Chitosan is naturally occurring bio-polymer having strong affinity towards transition metal ions. Chitosan complexed with transition metal ions takes up inorganic arsenic anions from aqueous medium. In present work, As(V) sorption in the chitosan complexed with different metal ions like Cu(II), Fe(III), La(III), Mo(VI) and Zr(IV) were studied. Sorptions of As(V) in CuS embedded chitosan, (3-aminopropyl) triethoxysilane (APTS) embedded chitosan, epichlorohydrin (ECH) crosslinked chitosan and pristine chitosan were also studied. (74)As radiotracer was prepared specifically for As(V) sorption studies by irradiation of natural germanium target with 18 MeV proton beam. The sorption studies indicated that Fe(III) and La(III) complexed with chitosan sorbed 95 ± 2% As(V) from aqueous samples in the pH range of 3-9. However, Fe(III)-chitosan showed better sorption efficiency (91 ± 2%) for As(V) from seawater than La(III)-chitosan (80 ± 2%). Therefore, Fe(III)-chitosan was selected to prepare the self-supported membrane and poly(propylene) fibrous matrix supported sorbent. The experimental As(V) sorption capacities of the fibrous and self-supported Fe(III)-chitosan sorbents were found to be 51 and 109 mg g(-1), respectively. These materials were characterized by XRD, SEM and EDXRF, and used for preconcentration of As(V) in aqueous media like tap water, ground water and seawater. To quantify the As(V) preconcentrated in Fe(III)-chitosan, the samples were subjected to instrumental neutron activation analysis (INAA) using reactor neutrons. As(V) separations were carried out using a two compartments permeation cell for the self-supported membrane and flow cell using the fibrous sorbent. The total preconcentration of arsenic content was also explored by converting As(III) to As(V).


Fusing Community-Engaged Learning & Transdisciplinary Curriculum for Undergraduate Community Development Education.
The Department of Community Development and Applied Economics at the University of Vermont embraces a transdisciplinary approach to community development education that provides students with real world experiences through community-engaged learning opportunities. The department was originally formed by an administrative decision that merged three departments in the College of Agriculture and Life Sciences intending to save financial resources. Over 25 years, we have developed a transdisciplinary approach that fills gaps that exist between disciplines that have yet to be closed while engaging with a variety of community partners to co-produce solutions to promote positive change. This article describes the evolution of our transdisciplinary curriculum that integrates a three-phased approach to service-learning. This framework enables faculty to offer appropriate service-learning experiences that provide meaningful interactions between students and community partners. CDAE has both honed and expanded curricular offerings to meet student interest and to better address community-based issues at the local, national, and global level.


Clinical management of resistance evolution in a bacterial infection: A case study.
We report the case of a patient with a chronic bacterial infection that could not be cured. Drug treatment became progressively less effective due to antibiotic resistance, and the patient died, in effect from overwhelming evolution. Even though the evolution of drug resistance was recognized as a major threat, and the fundamentals of drug resistance evolution are well understood, it was impossible to make evidence-based decisions about the evolutionary risks associated with the various treatment options. We present this case to illustrate the urgent need for translational research in the evolutionary medicine of antibiotic resistance.


Allosteric regulation of the cofactor-dependent serine protease coagulation factor VIIa.
The integration of structure and function analysis of the tissue factor-factor VIIa complex has provided a detailed view of the functional surface of the extrinsic activation complex. An incomplete zymogen to enzyme transition is responsible for the strict cofactor dependence of catalytic function of factor VIIa. The mutational analysis demonstrates that factor VIIa is allosterically regulated by specific conformational linkages that involve the cofactor binding site, the catalytic cleft, and the macromolecular substrate exosite. Regions of the flexible activation domain appear to play an important role in the allosteric regulation of this cofactor-dependent coagulation serine protease.


Novel porcine reproductive and respiratory syndrome virus strains in the United States with deletions in untranslated regions.
Porcine reproductive and respiratory syndrome (PRRS) still causes major problems for the swine industry worldwide. Here, we report the detection and genomic characterization of two novel PRRS virus (PRRSV) strains from the United States with deletions in untranslated regions (UTRs). The OH155-2015 strain has two single-nucleotide deletions in the 5' UTR, whereas the OH28372-2013 strain has a 13-nt deletion in the 3' UTR. In addition, OH155-2015 and OH28372-2013 have a unique deletion and mutations in the NSP2 and N gene, respectively. Our study highlights the importance of continued monitoring of PRRSV using whole-genome sequencing.


Safety and Efficacy of 177 Lu-DOTATATE in Neuroendocrine Tumor Patients With Extensive Bone Disease.
The aim of this study was to assess the efficacy and safety of 177 Lu-DOTATATE in patients with neuroendocrine tumors (NETs) and extensive bone metastases, that is, more than 50% of the skeleton involved. A single-center retrospective analysis was performed in 30 patients (13 women and 17 men, mean age, 60 years; range, 35-77 years) undergoing 177 Lu-DOTATATE therapy. Patients had progressive metastatic NETs with extensive skeletal metastases (>50% skeletal involvement seen on baseline 68 Ga-DOTATATE PET/CT). The average administered activity was 7.308 (SD, 0.02) GBq per cycle with average treatment interval of 15 weeks. Survival analyses (progression-free survival [PFS], overall survival), radiological response assessment, toxicity assessment, and health-related quality of life (QoL) was performed. Overall, 26 patients completed 4 cycles, and 4 patients had less than 4 cycles of 177 Lu-DOTATATE. One patient (3%) did not complete treatment because of hematological toxicity. The estimated median PFS and median overall survival were calculated at 27 and 35 months, respectively. End-of-treatment radiological assessment showed partial response in 5 patients (17%), stable disease in 20 patients (66%), and radiological progressive disease in 3 patients (10%). Clinical progression was seen in a further 2 patients (7%).The incidence of grade 3/4 bone marrow toxicity was 10%. No patient had grade 3/4 peptide receptor radionuclide therapy-related nephrotoxicity. There was overall improvement in global QoL score (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Gastrointestinal NET-21) ( P = 0.019). 177 Lu-DOTATATE seems to have satisfactory therapeutic outcome in patients with advanced metastatic NET with extensive bone disease, with reasonable PFS and significant improvement in the global health-related QoL. The bone marrow toxicity was within the accepted range. Increasing the interval between cycles does not seem to reduce efficacy and may reduce toxicity, ensuring the bone marrow has sufficient time to recover between cycles.


Accumbal dopamine function in postpartum rats that were raised without their mothers.
Postpartum rats that had been previously raised in an artificial rearing (AR) apparatus, without their mothers or siblings during the preweaning period, show altered maternal responses towards their own offspring in adulthood. In mother-reared (MR) rats, nucleus accumbens (NAC) dopamine (DA) responses to pups evoke a robust sustained rise during the postpartum period and following treatment with estrogen/progesterone parturient-like hormones (Afonso et al., 2009). These MR females had siblings that received AR rearing with varying amounts of preweaning tactile stimulation (ARmin; ARmax). The present study examined NACshell DA responses to pup and food stimuli in these AR rats, and statistically compared them to their MR siblings. Microdialysis samples were collected from adult (90 days postnatal) AR females in different parity states (cycling vs. postpartum, Exp. 1), or after ovariectomy with different hormone treatments (sham vs. hormone, Exp. 2. After basal sample collection, pup and then food stimuli were individually presented to the females in the dialysis chamber. As with their MR siblings, basal DA concentrations were lower and pup-evoked DA responses greater in hormonally-primed AR females than in non-primed AR controls. Compared to their postpartum MR sisters (Exp. 1), AR rats had increased basal DA levels, reduced pup related DA elevations, and disrupted maternal behavior. The postpartum AR impairment in pup-evoked DA was reversed by additional pre-weaning tactile stimulation. Exogenous hormones (Exp. 2) eliminated AR impairments on pup-evoked DA responses. Although MR and AR siblings had comparable DA responses to food stimuli, upon reanalyzing MR data it was found that only postpartum dams had DA responses to pups greater than to food. These data suggest that that the hormonally induced suppression of basal DA levels may reflect saliency of pups which was greater in MR than in AR dams. Preweaning tactile stimulation could partially reverse these effects only in naturally cycling or parturient animals.


Quantitative analysis of berberine in urine samples by chemical ionization mass fragmentography.
A highly specific and sensitive method has been developed for the quantitative determination of berberine in human urine. In order to carry out the microdetermination of berberine by chemical ionization mass fragmentography, berberine was reduced with sodium borohydride in methanol to tetrahydroberberine and subjected to gas chromatography-mass spectrometry. Berberine concentrations as low as 1 ng/ml urine can be measured by this method, with [2H3]berberine chloride as an internal standard.


Protein synthesis on membrane-bound and free ribosomes in growing yeast.
1. A method for the study of membrane-binding of ribosomes and the rate of synthesis of protein on free and bound ribosomes has been examined critically. 'Brij 58' has been found to be more suitable for detaching ribosomes from membranes than 'Triton X-100' or sodium deoxycholate since it does not alter the structure or biological activity of the ribosomes. Triton and deoxycholate remove amino acid- and ribonucleotide-containing material from ribosomes, thus decreasing their activity during protein synthesis in a cell free system. 2. The rate of protein synthesis on membrane-bound and free ribosomes, the total amount of ribosomes, and the percentage distribution of free and membrane-bound ribosomes were determined in a culture of synchronously growing yeast cells. The results show that in all probability protein synthesis in yeast cells occurs mainly on membrane-bound ribosomes. Free ribosomes are considered here to be a ribosome pool which allows the cell to increase its rate of protein synthesis rapidly. Membrane-bound and free ribosomes are viewed as different functional states, one being a state of protein synthesis and the other a latent state.


Critical evaluation of fast size exclusion chromatographic separations of protein aggregates, applying sub-2 μm particles.
A new size exclusion chromatography column packed with 1.7 μm particles and possessing 200 Å pore size has been critically evaluated for the determination of proteins and monoclonal antibody aggregates. In a first instance, the kinetic performance of this column was compared with that of a conventional column packed with 5 μm particles and with a recently launched 3 μm material, also possessing 200 Å pore size. In average, 2-5 times lower plate height were achieved on the 1.7 μm packing, compared with the conventional 5 μm particles. It was also demonstrated that elevated mobile phase temperature (up to 50 or 60 °C) allows improving the kinetic efficiency by 20-40% in size exclusion chromatography, compared to 30 °C. On the other hand, the new 3 μm material performed only slightly lower kinetic efficiency than the 1.7 μm one. When considering the upper pressure and temperature limits of these three columns, the 1.7 μm column systematically outperforms the 5 and 3 μm materials in the "practical" plate number range (N<30,000) and analysis times could be cut by 2-4 times. The column packed with 5 μm particles was only beneficial for plate counts beyond 100,000 plates, while the 3 μm packing could be considered as a good compromise between speed, efficiency and pressure. Besides the excellent kinetic performance of 1.7 μm size exclusion material under high temperature conditions, some artifacts were observed when quantifying protein aggregates. Indeed, both high pressure observed with 1.7 μm particles (shear forces, frictional heating) and elevated temperature produce some non negligible amount of on-column additional protein aggregates.


Anti-inflammatory activity of Agave intermixta Trel. and Cissus sicyoides L., species used in the Caribbean traditional medicine.
Agave intermixta Trel. and Cissus sicyoides L. are two tropical plants originating from the Dominican Republic. Aqueous extracts from these species are used in traditional medicine. In contrast, biological activity and toxicity of these plants are not yet evaluated systematically. The aim of the present work is to investigate a potential anti-inflammatory activity, and to elucidate the toxicity of the extracts. No lethal effects were produced after oral administration of the extracts. The values of the medium lethal doses after intraperitoneal administration were quite high for both species, although A. intermixta seems to be rather more toxic than C. sicyoides. The anti-inflammatory effects have been investigated in two experimental in vivo models. The carrageenan-induced rat paw oedema was chosen as a model for general inflammation, and the mice ear oedema test using tetradecanoylphorbol acetate as inflammatory agent as a model of topical inflammation. Dry extracts from decoctions of A. intermixta leaves and C. sicyoides stems were administered in doses of 300 and 500 mg/kg (p.o.) in the general model, and in doses of 3 and 5 mg/mouse ear for both plants in the topical model. In the general anti-inflammation assay, the oral administration of both extracts produced a significant anti-inflammatory effect, most pronounced for A. intermixta than for C. sicyoides. In the topical model, the administration of both extracts produced similar inhibitions of the oedema, with a reduction of approximately 50% in comparison with the control group. In homogenated tissue samples from the inflamed areas, a distinct decrease in the level of myeloperoxidase enzyme was noted.


Acute traumatic disruption of a bicuspid aortic valve.
Cardiac involvement is frequent in patients with blunt chest trauma and multiple injuries. Different cardiac structures can be involved, but isolated aortic valve rupture is rare. We report the case of a man admitted to our hospital with multiple injuries as a result of a car crash. Transthoracic, followed by transesophageal echocardiography, revealed disruption of a large anterior bi-coronary cusp in a bicuspid valve with severe aortic regurgitation, without lesions or abnormalities of thoracic aorta. Aggressive pharmacological management consented to delay valve replacement to obtain resolution of concomitant pulmonary injuries.


Rheumatic effects of vibration at work.
Occupational exposures to vibration come in many guises, and they are very common at a population level. It follows that an important minority of working-aged patients seen by medical services will have been exposed to this hazard of employment. Vibration can cause human health effects, which may manifest in the patients that rheumatologists see. In this chapter, we identify the health effects of relevance to them, and review their epidemiology, pathophysiology, clinical presentation, differential diagnosis and vocational and clinical management. On either side of this, we describe the nature and assessment of the hazard, the scale and common patterns of exposure to vibration in the community and the legal basis for controlling health risks, and we comment on the role of health surveillance in detecting early adverse effects and what can be done to prevent the rheumatic effects of vibration at work.


Application of confocal laser scanning microscopy to the deep pineal gland and other neural tissues.
The study of the deep pineal gland of the Mongolian gerbil and other neuronal tissue from the rat by means of confocal laser scanning microscopy (CLSM) is described. Opical serial sectioning was performed on thick (100-200 microns) sections of the deep pineal gland of the Mongolian gerbil stained immunohistochemically using antisera to S-antigen and tyrosine hydroxylase (TH). Both dual-stained and single-stained material was examined using the fluorochromes fluorescein isothiocyanate (FITC) and Texas Red. High resolution images were obtained showing that pinealocytes have 1-3 processes that extend primarily to other pinealocytes or presumptive pinealocytes. Pinealocytes are located within the deep pineal gland as well as adjacent to the posterior aspect of the medial habenular nuclei. Pinealocyte processes were not seen extending into the habenular nuclei, but rather ended within the deep pineal gland a significant distance from their perikarya. The TH-immunopositive fibers were distributed throughout the deep pineal gland, often forming "baskets" of fibers around pinealocytes rather than being associated primarily with blood vessels. Other uses of the confocal microscope are demonstrated on rat neural tissue reacted with peroxidase/diaminobenzidine (DAB) immunohistochemistry and FITC fluorescence immunohistochemistry (paraventricular nucleus) as well as Golgi-stained neuronal tissue (cerebral cortex). The HRP/DAB and Golgi-stained images were visualized using the reflected image mode of the confocal system.(ABSTRACT TRUNCATED AT 250 WORDS)


Etiology of chronic calcifying pancreatitis in Brazil: a report of 329 consecutive cases.
The authors observed 329 consecutive cases of chronic calcifying pancreatitis (CCP) from January 1963 to January 1986. Alcoholism was the etiological agent in 282 cases (86%). In 34 patients (10%) no cause was detectable (idiopathic). Malnutrition was responsible for 10 cases (3%) and chronic familial pancreatitis was diagnosed in 3 cases (0.9%). The mean age at the apparent onset of symptoms was 36.5 +/- 10.5 for the alcoholics, 22.6 +/- 15.4 in the idiopathic cases and 7.3 +/- 3.0 for the nutritional etiology patients. Mean age differences are statistically significant for the 3 groups. Pancreatic calcifications were found in 224 alcohol-induced cases (79%), in 32 idiopathic cases (94%), in 8 patients with malnutrition (80%) and in one patient with familial pancreatitis (33%). All cases of nutritional etiology presented severe protein-caloric deficiencies with edema, and none complained of pain, but 9 had pancreatic insufficiency. Mean daily ethanol intake for the alcohol-addicted patients was 396.6 +/- 286 g (range 80-1664 g) with the onset of alcoholism at 19.1 +/- 6.8 yr old and 20.8 +/- 8.3 (4-44) yr of alcohol indulgence. Pancreatic carcinoma developed in 7 cases. Six cases of chronic pancreatitis were seen among relatives in the group with CCP of alcoholic etiology.


Home-based physical activity intervention for colorectal cancer survivors.
The efficacy of a home-based physical activity (PA) intervention for colorectal cancer patients versus contact control was evaluated in a randomized controlled trial. Forty-six patients (mean age = 57.3 years [SD = 9.7], 57% female, mean = 2.99 years post-diagnosis [SD = 1.64]) who had completed treatment for stages 1-3 colorectal cancer were randomized to telephone counseling to support PA (PA group, n = 20) or contact control (control group, n = 26). PA group participants received 3 months of PA counseling (based on the transtheoretical model and the social cognitive theory) delivered via telephone, as well as weekly PA tip sheets. Assessments of PA (Seven-day Physical Activity Recall [7-day PAR] and Community Healthy Activities Model Program for Seniors [CHAMPS]), submaximal aerobic fitness (Treadwalk test), motivational readiness for PA, and psychosocial outcomes were conducted at baseline, 3, 6, and 12 months post-baseline. Objective accelerometer data were collected at the same time points. The PA group reported significant increases in minutes of PA at 3 months (7-day PAR) and caloric expenditure (CHAMPS) compared with the control group, but the group differences were attenuated over time. The PA group showed significant improvements in fitness at 3, 6, and 12 months versus the control group. Improvements in motivational readiness for PA were reported in the PA group only at 3 months. No significant group differences were found for fatigue, self-reported physical functioning, and quality of life at 3, 6, and 12 months. A home-based intervention improved survivors' PA and motivational readiness at 3 months and increased submaximal aerobic fitness at 3, 6, and 12 months.


Autism and Rett syndrome: behavioural investigations and differential diagnosis.
The most common wrong diagnosis of children with Rett syndrome has been the infantile autistic syndrome, and it is probable that this false diagnosis continues to be made in many places. This paper is a follow-up to the authors' previous study concerning differential diagnosis between the two syndromes and is based on the observation of 63 patients over the age of 22 months in 10 stimulus situations. In Rett syndrome there were very small individual differences in the sensorimotor performances, which correspond only to the third and fourth stages of Piaget's 'sensorimotor intelligence' scale. There were pronounced individual differences in the levels of basic motor development and, independently from these, in autistic behavioural traits. When the children's behaviour was examined in detail, it became evident that girls with Rett syndrome differ in many subtle ways from those with the autistic syndrome. Behaviour observed in some cases of Rett syndrome but in none of the autistic syndrome included: social (non-autistic) behaviour; no chewing, at most sucking of items of food placed in the mouth; monotonous 'hand-washing' movements with arms flexed in front of chest or chin. In all cases of Rett syndrome but in only some of the autistic syndrome there were: no 'social defence reactions' nor 'primary self-injuring activities'; some form of ataxia and a very restricted repertoire of postures and movements, monotonous in form and speed; and the time spent looking at objects and people was at least as long as the time taken to manipulate objects. Some causes of the characteristic stereotypic hand movements observed in Rett syndrome are also suggested.


Deletion of the Transient Receptor Potential Vanilloid 1 Channel Attenuates Sympathoexcitation and Hypertension and Improves Glomerular Filtration Rate in 2-Kidney-1-Clip Rats.
Renal denervation lowers arterial blood pressure in both clinical populations and multiple experimental models of hypertension. This therapeutic effect is partly attributed to the removal of overactive renal sensory nerves. The TRPV1 (transient receptor potential vanilloid 1) channel is highly expressed in renal sensory nerves and detects changes in noxious and mechanosensitive stimuli, pH, and chemokines. However, the extent to which TRPV1 channels contribute to 2-kidney-1-clip (2K1C) renovascular hypertension has not been tested. We generated a novel Trpv1-/- (TRPV1 knockout) rat using CRISPR/Cas9 and 26-bp deletion in exon 3 and induced 2K1C hypertension. The majority (85%) of rat renal sensory neurons retrogradely labeled from the kidney were TRPV1-positive. Trpv1-/- rats lacked TRPV1 immunofluorescence in the dorsal root ganglia, had a delayed tail-flick response to hot but not cold water, and lacked an afferent renal nerve activity response to intrarenal infusion of the TRPV1 agonist capsaicin. Interestingly, 2K1C hypertension was significantly attenuated in male Trpv1-/- versus wild-type rats. 2K1C hypertension significantly increased the depressor response to ganglionic blockade, total renal nerve activity (efferent and afferent), and afferent renal nerve activity in wild-type rats, but these responses were attenuated in male Trpv1-/- rats. 2K1C hypertension was attenuated in female rats with no differences between female strains. Finally, glomerular filtration rate was reduced by 2K1C in wild-type rats but improved in Trpv1-/- rats. These findings suggest that renovascular hypertension requires activation of the TRPV1 channel to elevate renal afferent and sympathetic nerve activity, reduce glomerular filtration rate, and increase arterial blood pressure.


Conductive hearing loss and speech development.
The central issue about conductive hearing loss and speech development is the impact of mild to moderate hearing loss that may be intermittent. Although opinions vary considerably about what this does to the ability of the child to learn, most studies support a position of concern. This concern should focus on identification and treatment of such children, with special teaching techniques in addition to medical and surgical treatment.


High-performance liquid chromatography with post-column derivatisation and fluorescence detection for sensitive determination of aflatoxin M1 in milk and cheese.
A new HPLC method with fluorescence detection using pyridinium hydrobromide perbromide as a post-column derivatising agent has been developed to determine aflatoxin M1 in milk and cheese. The detection limits were 1 ng/kg for milk and 5 ng/kg for cheese. The calibration curve was linear from 0.001 to 0.1 ng injected. The method includes a preliminary C18-SPE clean-up and the average recoveries of Aflatoxin M1 from milk and cheese, spiked at levels of 25-75 ng/kg and 100-300 ng/kg, respectively, were 90 and 76%; the precision (RSDr) ranged from 1.7 to 2.6% for milk and from 3.5 to 6.5% for cheese. The method is rapid, easily automatable and therefore useful for accurate and precise screening of aflatoxin M1 in milk and cheese.


Deprescribing in Frail Older People: A Randomised Controlled Trial.
Deprescribing has been proposed as a way to reduce polypharmacy in frail older people. We aimed to reduce the number of medicines consumed by people living in residential aged care facilities (RACF). Secondary objectives were to explore the effect of deprescribing on survival, falls, fractures, hospital admissions, cognitive, physical, and bowel function, quality of life, and sleep. Ninety-five people aged over 65 years living in four RACF in rural mid-west Western Australia were randomised in an open study. The intervention group (n = 47) received a deprescribing intervention, the planned cessation of non-beneficial medicines. The control group (n = 48) received usual care. Participants were monitored for twelve months from randomisation. Primary outcome was change in the mean number of unique regular medicines. All outcomes were assessed at baseline, six, and twelve months. Study participants had a mean age of 84.3 ± 6.9 years and 52% were female. Intervention group participants consumed 9.6 ± 5.0 and control group participants consumed 9.5 ± 3.6 unique regular medicines at baseline. Of the 348 medicines targeted for deprescribing (7.4 ± 3.8 per person, 78% of regular medicines), 207 medicines (4.4 ± 3.4 per person, 59% of targeted medicines) were successfully discontinued. The mean change in number of regular medicines at 12 months was -1.9 ± 4.1 in intervention group participants and +0.1 ± 3.5 in control group participants (estimated difference 2.0 ± 0.9, 95%CI 0.08, 3.8, p = 0.04). Twelve intervention participants and 19 control participants died within 12 months of randomisation (26% versus 40% mortality, p = 0.16, HR 0.60, 95%CI 0.30 to 1.22) There were no significant differences between groups in other secondary outcomes. The main limitations of this study were the open design and small participant numbers. Deprescribing reduced the number of regular medicines consumed by frail older people living in residential care with no significant adverse effects on survival or other clinical outcomes. Australian New Zealand Clinical Trials Registry ACTRN12611000370909.


Gender disparity in utilization rates of substance abuse services among female ex-offenders: a population-based analysis.
The use and abuse of substances is common among offender populations. Although the female former offender population has risen substantially in recent decades, relatively little is known about their substance abuse treatment experiences. This study examines disparities in substance abuse treatment utilization among the US population with special focus upon formerly incarcerated female offenders. Using data from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC, n = 43,093) collected in 2001-2002 and 2004-2005 the authors compared lifetime rates of substance abuse treatment utilization between female and male ex-offenders with the U.S. general population. The sample population covered inpatient and community based substance use treatment, detoxification and rehabilitation programs. It is a nationally representative sample of noninstitutionalized persons over the age of 18. Multinomial logistic regression was performed and likelihood of using substance use treatment and services was calculated using adjusted odds ratios (AOR). Compared to male ex-offenders, female ex-offenders were 52% less likely to use substance-abuse treatment services (AOR = 0.48, 95% CI = 0.26-0.89) and 51% less likely to use rehabilitation programs (AOR = 0.49, 95% CI = 0.26-0.93). Compared to females in the general population, female ex-offenders were 10 times more likely to use substance-abuse treatment services (AOR = 10.14, 95% CI = 5.71-18.00), 10.5 times more likely to use substance detoxification programs (AOR = 10. 45, 95% CI = 5.64-19.39); 8 times more likely to use inpatient wards (AOR = 8.05, 95% CI = 4.16-15.59); 9 times more likely to use outpatient wards (AOR = 9.06, 95% CI = 4.89-16.81), and 12 times more likely to use substance-abuse rehabilitation programs (AOR = 12.06, 95% CI = 6.55-22.22). While female ex-offenders were more likely to have used a range of substance abuse services when compared to the general population, they were less likely to use substance-abuse treatment services and rehabilitation programs than male ex-offenders.


ERCC1 C8092A polymorphism predicts fair survival outcome in Japanese patients with pharyngo-laryngeal squamous cell carcinoma.
To evaluate the prognostic significance of DNA excision repair gene polymorphisms, excision repair cross-complementation group 1 (ERCC1) and X-ray repair complementing defective repair in Chinese hamster cells 1 (XRCC1) polymorphisms were investigated in Japanese patients with head and neck squamous cell carcinoma (HNSCC). A total of 225 consecutive patients with HNSCC who underwent surgery or chemoradiotherapy/radiotherapy (CRT/RT) with curative intent as primary treatment from 2006 to 2017 were recruited. ERCC1 C8092A and XRCC1 Arg399Gln polymorphisms in DNA extracted from individual blood samples were determined by the polymerase chain reaction-restriction fragment length polymorphism method. Cumulative survival was estimated by Kaplan-Meier analysis with a log-rank test and Cox proportional hazards model stratified by treatment arm, adjusting for clinical prognostic factors. Multivariate analysis showed that carriers with the ERCC1 8092 (C/A+A/A) genotype (hazard ratio, 3.56; 95% confidence interval, 1.22-7.39; p = 0.02) had significantly worse survival than those with ERCC1 8092 C/C who received CRT/RT. Conversely, the XRCC1 Arg399Gln polymorphism did not influence survival in patients who received CRT/RT as well as surgery. The ERCC1 C8092A polymorphism might be an independent predictor of response to CRT and survival outcome in patients with HNSCC. This is the first report to investigate the role of DNA excision repair gene polymorphisms in patients with head and neck cancer in a Japanese population.


Intra-arterial versus intra-venous thrombolysis within and after the first 3 hours of stroke onset.
The NINDS trial demonstrated for the first time the effectiveness of intravenous thrombolysis in improving outcome after acute ischemic stroke. The absolute benefit of this intervention was 11-13% greater chance of being normal or near normal (MRS ≤ 1) at 3 months. However, if patients with severe stroke were considered (NIHSS ≥ 20), the absolute benefit dropped to 5-6%, indicating that IV thrombolysis may not be as effective for large vessel occlusion. This observation was further supported by TCD studies that clearly demonstrated that large artery occlusions had a recanalization rate of 13-18% with IV rt-PA. Intra-arterial thrombolysis achieves recanalization rates of 60-70%. Since tissue viability is clearly important, it is time to stop defining rigid time windows and if there is a large penumbra (20-50%) and the occlusion is in a large artery, there exists a logic and a growing evidence to consider either bridge therapy or direct intra-arterial therapy.


Communication Between Breast Cancer Patients Who Received Inconclusive Genetic Test Results and Their Daughters and Sisters Years After Testing.
Inconclusive genetic test results including screening recommendations for the breast cancer patients and their first-degree relatives are the most common outcomes of BRCA 1/2 testing. Patients themselves should communicate these results to their relatives. Our aim was to explore communication of breast cancer genetic counseling results with daughters and sisters over a long period of time. Breast cancer patients, who had received an inconclusive DNA test result 7-14 years earlier, completed a self-report questionnaire. Additionally, in-depth interviews were conducted and analysed thematically. Of the 93 respondents, 85 (91 %) considered themselves responsible for communicating genetic test results to relatives. In-depth interviews (n = 14) showed, that counselees wanted 'to hand over' their responsibilities to communicate the test results and screening recommendations to their sisters. Although most patients had informed their daughters and sisters about the genetic test results, usually little is spoken about genetic test results and screening recommendations once the duty of informing is completed. We recommend that, similar to the procedure for BRCA1/2-mutation carriers, a separate letter for first-degree relatives of patients with an inconclusive test result should be provided. In this way information about risks and screening recommendations can be verified by family members years after genetic testing has been completed.


[Correlation of testis/sperm specific thioredoxin-1, 2 and 3 with male reproduction].
Sptrx-1, 2 and 3 are a series of thioredoxins specifically expressed in the testis/sperm. They play a significant role structurally and functionally in the process of spermiogenesis. The genesis and mutation of sptrx-1, 2 and 3 are correlated to male reproduction. Taking sptrx-1, 2 and 3 as the target of study and treatment will open up a new field in the clinical study of male reproduction.


Assessment of VOR gain function and its test-retest reliability in normal hearing individuals.
Video head impulse test (vHIT) aids to assess all three pairs of semi-circular canals (SCCs) separately and can be utilized to find out the exact site of lesion in any three SCCs by measuring vestibulo ocular reflex (VOR) gain. VOR gain value of vHIT has been used to diagnose different vestibular pathologies. Hence, it is important to establish the test-retest reliability of the VOR gain parameters before it could be administered to the patients. Therefore, the aim of the present study was to obtain VOR gain data, correlate all planes in both sides of head (right and left) and assess the test-retest reliability of VOR gain measure using vHIT in 25 normal young adult participants. Video head impulse test tests were carried out with prototype ICS impulse video goggles with a camera speed of 250 frames/s, recording motion of the right eye in all three planes (lateral, right anterior left posterior, left anterior right posterior) for all the participants. vHIT testing was repeated for all the participants after 15 days. Statistical analysis revealed that mean VOR gain for right horizontal canal was higher than the left horizontal canal; right anterior canal was higher than left anterior canal and left anterior was higher than right posterior canal. Horizontal canals have more gain compared to anterior and posterior canals. There was no significant difference between the VOR gain of session 1 and session 2 for each SCC.


Fabrication of optimal oxygen vacancy amount in P/Ag/Ag2O/Ag3PO4/TiO2 through a green photoreduction process for sustainable H2 evolution under solar light.
Defects engineering on photocatalysts such as oxygen vacancies (OVs) is an effective approach for improving photocatalytic hydrogen (H2) evolution efficiency. In this study, OVs modified P/Ag/Ag2O/Ag3PO4/TiO2 (PAgT) composite was successfully fabricated via a photoreduction process by controlling the ratio of PAgT to ethanol (16, 12, 8, 6 and 4 g·L-1) under simulated solar light irradiation for the first time. Characterization methods confirmed the presence of OVs in the modified catalysts. Meanwhile, the OVs amount and their effects on the light absorption ability, charge transfer rate, conduction band and H2 evolution efficiency of the catalysts were also investigated. The results indicated that the optimal OVs amount endowed OVs-PAgT-12 with the strongest light absorption, the fastest electron transfer rate and suitable band gap for H2 evolution, leading to the highest H2 yield (863 μmol·h-1·g-1) under solar light irradiation. Moreover, OVs-PAgT-12 exhibited a superior stability during cyclic experiment, indicating its great potential for practical application. Furthermore, a sustainable H2 evolution process was proposed based on a combination of sustainable bio-ethanol resource, stable OVs-PAgT, abundant solar energy and recyclable methanol. This study would provide new insights into the design of defects modified composite photocatalyst for enhanced solar-to-hydrogen conversion.


Interaction of onconase with the human ribonuclease inhibitor protein.
One of the tightest known protein-protein interactions in biology is that between members of the ribonuclease A superfamily and the ribonuclease inhibitor protein (RI). Some members of this superfamily are able to kill cancer cells, and the ability to evade RI is a major determinant of whether a ribonuclease will be cytotoxic. The archetypal cytotoxic ribonuclease, onconase (ONC), is in late-stage clinical trials for the treatment of malignant mesothelioma. We present here the first measurement of the inhibition of the ribonucleolytic activity of ONC by RI. This inhibition occurs with K(i)=0.15muM in a solution of low salt concentration.


The alcohol use disorders identification test: reliability study of the Japanese version.
Alcohol abuse is recognized as a major health issue, and early detection of alcohol abuse is very important. The alcohol use disorders identification test (AUDIT) has been widely used as a specific tool for its detection. We conducted a cross-sectional survey of Japanese male workers to validate the Japanese version of this test. The Japanese version of AUDIT also contains 10 questions. A score greater than or equal to 11 was considered as indicative of serious alcohol abuse or dependence. A total of 168 subjects took part in the survey, and 145 of these subjects sent in their responses to the questionnaire. Among these 145 subjects, there were 136 men. The average age of these male subjects was 38.2 years (±9.9). Among the 136 male subjects, 113 returned completely filled-in questionnaires. There were no significant differences in the mean values of the AUDIT score, short version of AUDIT (AUDIT-C) score, or age between the subjects who did or did not indicate their names in the questionnaire. The internal reliability (Cronbach alpha) of AUDIT was 0.67 for the total subject population and 0.45 for the subjects who indicated their names in the questionnaire (n=69). Cronbach's alpha of AUDIT-C was 0.51 for the total subject population and 0.43 for the subjects who indicated their names in the questionnaire. The Spearman's rho between AUDIT and AUDIT-C was 0.92 (P<.01), and the percentage of subjects with an AUDIT score greater than or equal to 11 was 8.0% (9/113). Thus, the Japanese version of AUDIT showed satisfactory internal reliability. AUDIT is easy to use and is useful for the detection of alcohol-related problems in occupational workers.


Study of trace elements in blood of thyroid disorder subjects before and after 131I therapy.
Both trace elements and thyroid hormones play essential roles in the human body. However, the previous results about the interaction between these two factors are often controversially given. In order to make clear the influence of thyroid hormones on the homeostasis of trace elements, we studied the variation of Fe, Cu, and Zn in erythrocyte and serum from patients with hyperthyroidism before and after 131I therapy by the X-ray fluorescence method. The different thyroid statuses of the patients before and after the therapy were assayed by determining the levels of thyroid hormones. The results showed that the homeostasis of metal ions in both serum and erythrocyte could be more or less influenced by the altered thyroid hormones. The serum Cu and Zn exhibited the significantly positive correlation with triiodothyronine (T3) and thyroxine (T4). Although the serum Cu and Zn differed significantly before and after the therapy, no difference was observed in the concentrations of Cu and Zn in erythrocyte, except that the erythrocyte Zn in the patients with hypothyroidism exhibited an obvious increase. Furthermore, the erythrocyte Zn showed a markedly negative correlation with T3.


Impact of different coils on biochemical T2 and T2* relaxation time mapping of articular patella cartilage.
The purpose of our study was to assess T2 and T2* relaxation time values of patella cartilage in healthy volunteers using three different coils at 3.0 Tesla MRI and their influence on the quantitative values. Fifteen volunteers were examined on the same 3-Tesla MR unit using three different coils: (i) a dedicated eight-channel knee phased-array coil; (ii) an eight-channel multi-purpose coil, and (iii) a one-channel 1H surface coil. T2 and T2* relaxation time measurements were prepared by a multi-echo spinecho respectively a gradient-echo sequence. A semi-automatic region-of-interest analysis was performed for patella cartilage. To allow stratification, a subregional analysis was carried out (deep-superficial cartilage layer). Statistical analysis-of-variance was performed. The mean quantitative T2 values showed statistically significant differences in all comparison combinations. The differences between the mean quantitative T2* values were slightly less pronounced than the T2 evaluation and only the comparison between (i) and (ii) showed a significant difference. The results of T2 and T2* values showed, independent of the used coil, higher values in the superficial zone compared to the deep zone (p < 0.05). Looking at the signal alterations, all coils showed clearly higher values (and thus more signal alterations as a sign of noise) in the deep layer. The validation of the reliability showed a high intra-class correlation coefficient and hence a very high plausibility (ICC was between 0.870 and 0.905 for T2 mapping and between 0.879 and 0.888 for T2* mapping). The present results demonstrate that biochemical T2 and T2* mapping is significantly dependent on the utilized coil.


Megavoltage external beam irradiation of craniopharyngiomas: analysis of tumor control and morbidity.
From 1971 to 1985, 21 patients received megavoltage external beam radiation therapy at the University of Pittsburgh for control of craniopharyngioma. Minimum tumor doses prescribed to the 95% isodose volume ranged between 51.3 to 70.0 Gy. Median total dose was 60.00 Gy and median dose per fraction was 1.83 Gy. Three deaths occurred from intercurrent disease and no deaths from tumor progression. Actuarial overall survival was 89% and 82% at 5 and 10 years. Actuarial local control was 95% at 5 and 10 years. Radiation related complications included one patient with optic neuropathy, one with brain necrosis, and one that developed optic neuropathy followed by brain necrosis. The high dose group of patients who received a NSD or Neuret equivalent of greater than 60 Gy at 1.8 Gy per fraction had a significantly greater risk of radiation complications (p = .024). The actuarial risk at 5 years for optic neuropathy was 30% and brain necrosis was 12.5% in the high dose group. Tumor control in the high dose group was not shown to be significantly better. Any possible benefit in tumor control in treating patients with craniopharyngioma with doses above 60 Gy at 1.8 Gy per fraction appears to be offset by the increased risk of radiation injury.


The use of non-living animals as simulation models for cranial neurosurgical procedures: a literature review.
Simulation plays a pivotal role in neurosurgical training by allowing trainees to develop the requisite expertise to enhance patient safety. Several models have been used for simulation purposes. Non-living animal models offer a range of benefits, including affordability, availability, biological texture, and a comparable similarity to human anatomy. In this paper, we review the available literature on the use of non-living animals in neurosurgical simulation training. We aim to answer the following questions: (1) what animals have been used so far, (2) what neurosurgical approaches have been simulated, (3) what were the trainee tasks, and (4) what was the experience of the authors with these models. A search of the PubMed Medline database was performed to identify studies that examined the use of non-living animals in cranial neurosurgical simulation between 1990 and 2020. Our initial search yielded a total of 70 results. After careful screening, we included 22 articles for qualitative analysis. We compared the reports in terms of the (1) animal used, (2) type of surgery, and (3) trainee tasks. All articles were published between 2003 and 2019. These simulations were performed on three types of animals, namely sheep, cow, and swine. All authors designed specific, task-oriented approaches and concluded that the models used were adequate for replicating the surgical approaches. Simulation on non-living animal heads has recently gained popularity in the field of neurosurgical training. Non-living animal models are an increasingly attractive option for cranial neurosurgical simulation training. These models enable the acquisition and refinement of surgical skills, with the added benefits of accessibility and cost-effectiveness. To date, 16 different microneurosurgical cranial approaches have been replicated on three non-living animal models, including sheep, cows, and swine. This review summarizes the experience reported with the use of non-living animal models as alternative laboratory tools for cranial neurosurgical training, with particular attention to the set of tasks that could be performed on them.


Glucocorticoid hypertension due to the use of bleaching skin cream, a case report.
We report on an unusual case of a 28-year old African woman who developed glucocorticosteroid induced arterial hypertension after abusive use of a skin bleaching cream. Glucocorticosteroids exert their effect at many different sites involved in blood pressure regulation: in particular at the level of the kidney, blood vessels and the heart. The exact incidence of arterial hypertension after prolonged cutaneous glucocorticosteroid administration is unknown. The mechanism of glucocorticosteroid induced hypertension is discussed.


Trends in Antibiotic Resistance Patterns and Burden of Escherichia Coli Infections in Young Children: A Retrospective Cross-Sectional Study in Shenzhen, China from 2014-2018.
The emergence of multi-drug resistant ESBL-producing E. coli poses a global health problem. In this study, we aimed to investigate the prevalence of E. coli infections and their antibiotic susceptibility profiles in paediatric clinical cases in Shenzhen, China from Jan 1, 2014, to Jan 30, 2019, while also determining temporal trends, identifying ESBL-producing strains, and recommending potential empirical antibiotic therapy options. We isolated a total of 4148 E. coli from different specimens from a single paediatric healthcare centre. Additionally, we obtained relevant demographic data from the hospital's electronic health records. Subsequently, we performed antimicrobial susceptibility testing for 8 classes of antibiotics and assessed ESBL production. Out of the 4148 isolates, 2645 were from males. The highest burden of E. coli was observed in the age group of 0-1 years, which gradually declined over the five-year study period. Antimicrobial susceptibility results indicated that 82% of E. coli isolates were highly resistant to ampicillin, followed by 52.36% resistant to cefazolin and 47.46% resistant to trimethoprim/sulfamethoxazole. Notably, a high prevalence of ESBL production (49.54%) was observed among the E. coli isolates, with 60% of them displaying a multi-drug resistance phenotype. However, it is worth mentioning that a majority of the isolates remained susceptible to ertapenem and imipenem. Our findings also highlighted a decrease in E. coli infections in Shenzhen, primarily among hospitalized patients in the 0-1 year age group. However, this decline was accompanied by a considerably high rate of ESBL production and increasing resistance to multiple antibiotics. Our study underscores the urgent need for effective strategies to combat multi-drug resistant ESBL-producing E. coli Infections.


Cardiorespiratory kinetics in exercise physiology: estimates and predictions using randomized changes in work rate.
Kinetics of cardiorespiratory parameters (CRP) in response to work rate (WR) changes are evaluated by pseudo-random binary sequences (PRBS testing). In this study, two algorithms were applied to convert responses from PRBS testing into appropriate impulse responses to predict steady states values and responses to incremental increases in exercise intensity. 13 individuals (age: 41 ± 9 years, BMI: 23.8 ± 3.7 kg m-2), completing an exercise test protocol, comprising a section of randomized changes of 30 W and 80 W (PRBS), two phases of constant WR at 30 W and 80 W and incremental WR until subjective fatigue, were included in the analysis. Ventilation ([Formula: see text]), O2 uptake ([Formula: see text]), CO2 output ([Formula: see text]) and heart rate (HR) were monitored. Impulse responses were calculated in the time domain and in the frequency domain from the cross-correlations of WR and the respective CRP. The algorithm in the time domain allows better prediction for [Formula: see text] and [Formula: see text], whereas for [Formula: see text] and HR the results were similar for both algorithms. Best predictions were found for [Formula: see text] and HR with higher (3-4%) 30 W steady states and lower (1-4%) values for 80 W. Tendencies were found in the residuals between predicted and measured data. The CRP kinetics, resulting from PRBS testing, are qualified to assess steady states within the applied WR range. Below the ventilatory threshold, [Formula: see text] and HR responses to incrementally increasing exercise intensities can be sufficiently predicted.


Fidelity and Feasibility of a Brief Emergency Department Intervention to Empower Adults With Serious Illness to Initiate Advance Care Planning Conversations.
Emergency department (ED) visits provide opportunities to empower patients to discuss advance care planning with their outpatient clinicians, but systematically developed, feasible interventions do not currently exist. Brief negotiated interview (BNI) interventions, which allow ED clinicians to efficiently motivate patients, have potential to meet this need. We developed a BNI ED intervention to empower older adults with life-limiting illness to formulate and communicate medical care goals to their primary outpatient clinicians. This study assessed the fidelity and feasibility of this intervention in a high-volume ED. We enrolled adult patients with serious illnesses (advanced cancer, congestive heart failure, chronic obstructive pulmonary disease, chronic kidney disease on dialysis, predicted survival <12 months) in an urban, tertiary care academic medical center ED. All participants received the BNI intervention. We video-recorded the encounters. Two reviewers assessed the recordings for intervention fidelity based on adherence to the BNI steps (Part I) and communication skills (Part II). We reviewed 46 video recordings. The mean total adherence score was 21.07/27 (SD 3.68) or 78.04%. The Part I mean adherence score was 12.07/15 (SD 2.07) or 80.47%. The Part II mean adherence score was 9.0/12 (SD 2.51) or 75%. The majority (75.6%) of recordings met the prespecified threshold for high intervention fidelity. ED clinicians can deliver a BNI intervention to increase advance care planning conversations with high fidelity. Future research is needed to study the intervention's efficacy in a wider patient population.


Molecular distributions and compound-specific stable carbon isotopic compositions of lipids in wintertime aerosols from Beijing.
Molecular distributions and stable carbon isotopic compositions (δ(13)C) of n-alkanes, fatty acids and n-alcohols were investigated in urban aerosols from Beijing, northern China to better understand the sources and long-range atmospheric transport of terrestrial organic matter during polluted and clear days in winter. n-Alkanes (C19-C36), fatty acids (C8-C32) and n-alcohols (C16-C32) detected in Beijing aerosols are characterized by the predominance of C23, C16 and C28, respectively. Carbon preference index (CPI) values of n-alkanes, the ratios of the sum of odd-numbered n-alkanes to the sum of even-numbered n-alkanes, are close to 1, indicating a heavy influence of fossil fuel combustion. Relatively higher ratios of C(18:0+16:0)/C(18:n+16:1) (fatty acids) on clear days than polluted days indicate that long-distance transport and/or photochemical aging are more significant during clear days. δ(13)C values of n-alkanes and low molecular weight fatty acids (C16:0, C18:0) ranged from -34.1 to -24.7% and -26.9 to -24.6%, respectively, which are generally heavier on polluted days than those on clear days. Such a wide range suggests that atmospheric lipids in Beijing aerosols originate from multiple sources and encounter complicated atmospheric processes during long-range transport in North China.


The acetylcholinesterase inhibitors competitively inhibited an acetyl L-carnitine transport through the blood-brain barrier.
We investigated the interaction of acetylcholinesterase (AChE) inhibitors with acetyl-L-carnitine (ALCAR) transporter at the blood-brain barrier (BBB). ALCAR uptake by conditionally immortalized rat brain capillary endothelial cell lines (TR-BBB cells), as an in vitro model of BBB, were characterized by cellular uptake study using [(3)H]ALCAR. In vivo brain uptake of [(3)H]ALCAR was determined by brain uptake index after carotid artery injection in rats. In results, the transport properties for [(3)H]ALCAR by TR-BBB cell were consistent with those of ALCAR transport by the organic cation/carnitine transporter 2 (OCTN2). Also, OCTN2 was confirmed to be expressed in the cells. The uptake of [(3)H]ALCAR by TR-BBB cells was inhibited by AChE inhibitors such as donepezil, tacrine, galantamine and rivastigmine, which IC(50) values are 45.3, 74.0, 459 and 800 μM, respectively. Especially, donepezil and galantamine inhibited the uptake of [(3)H]ALCAR competitively, but tacrine and rivastigmine inhibited noncompetitively. Furthermore, [(3)H]ALCAR uptake by the rat brain was found to be significantly decreased by quinidine, donepezil and galantamine. Our results suggest that transport of AChE inhibitors such as donepezil and galantamine through the BBB is at least partly mediated by OCTN2 which is involved in transport of ALCAR.


Involvement of p53 mutation in the development of human salivary gland pleomorphic adenomas.
We examined the status of the p53 mutation, a putative tumor suppressor gene, as well as the expressions of myc and mos oncogene products in human salivary gland pleomorphic adenoma cells in culture derived from four individuals using techniques which enabled selective and favourable growths of tumor cells. Culture techniques empolyed in this study consisted of type I collagen gel-coated dishes and serum-free medium as substrates and growth medium, respectively. Cells grown under above conditions were subjected to the analyses of p53, myc and mos expression. When analyzed by both immunocytochemical staining and immunoblot, mutant forms of p53 specifically detected by PAb240 were observed in three of 4 cases. However, none of the 4 cases expressed myc and mos oncogene products. These results may imply a role for p53 mutation in the development of human salivary gland pleomorphic adenomas.


Menstrual hygiene practices among adolescent women in rural India: a cross-sectional study.
Exclusive use of hygienic methods (sanitary napkins, locally prepared napkins, tampons, and menstrual cups) to prevent the visibility of bloodstains during menstruation is still considerably low among adolescent women in rural India. However, no prior research has explored the prevalence and determinants of exclusive hygienic methods among rural Indian adolescent women. To address this gap, this study examines the factors affecting adolescent women's exclusive use of hygienic methods in rural India. Additionally, this study explores state- and district-level geographical disparities in the exclusive use of hygienic methods among adolescent women in rural India. Information on 95,551 adolescent women from rural India from the latest round of National Family Health Survey (NFHS-5) was analyzed. Bivariate statistics and multilevel logistic regression analysis were used to assess the Individual- and community-level factors associated with exclusive use of hygienic methods among adolescent women in rural India. Choropleth maps were used to discern the geographical disparities in the exclusive use of hygienic methods. In rural India, only 42% of adolescent women exclusively used hygienic methods, with substantial geographic disparities at the state and district levels. At the state level, the exclusive use of hygienic methods varied from 23% in Uttar Pradesh to 85% in Tamil Nadu. Even greater variation was observed at the district level. There was a clear north-south divide in the exclusive use of hygienic methods among adolescent women in rural India. The results of multilevel logistic regression indicated a considerable amount of variation in the exclusive use of hygienic methods at community level which further reduced when controlled for individual and community-level factors. Rural Indian adolescent women with higher education (AOR:3.20, 95% CI: 2.81-3.64), from general category (AOR: 1.14, 95% CI: 1.07-1.21), with medium mass media exposure (AOR: 1.43, 95% CI: 1.35-1.51), and from richest wealth quintile (AOR: 3.98, 95% CI: 3.69-4.30) were more likely to use hygienic methods exclusively. Wide differential across biodemographic and socioeconomic groups, and substantial geographic disparities at state- and district-level in the exclusive use of hygienic methods suggests a need to adopt context-specific interventions for adolescent women in rural India. Distribution of subsidized or free menstrual hygiene methods to disadvantaged adolescent women, and in the low-prevalence districts may increase the level of exclusive use of hygienic methods remarkably.


A modified surgical/prosthetic approach for optimal single implant supported crown. Part I--The socket seal surgery.
Optimal implant placement can be achieved only if the ridge maintains its dimensions and the quality of bone. To prevent the resorption of the ridge and to enhance the quality of regenerated bone, two main approaches have been suggested. Part I of this article presents a modified regenerative technique-the "socket seal surgery" (SSS). Part II will present a modified prosthetic technique--the "cervical contouring concept" (CCC)--and it will be published in the May, 1994, issue of PP&A. The learning objective of this article is to supplement reader knowledge of methods and techniques for prevention of ridge resorption and enhancement of bone regeneration.


A novel eurythermic and thermostale lipase LipM from Pseudomonas moraviensis M9 and its application in the partial hydrolysis of algal oil.
Lipases are regularly used in biotechnology to catalyse the hydrolysis of triglycerides and the synthesis of esters. Microbial lipases in particular have been widely used in a variety of industrial applications. However, the current commercial microbial lipases cannot meet industrial demand due to rapid inactivation under harsh conditions. Therefore, in order to identify more stable enzymes, we isolated novel eurythermic and thermostable lipase(s) from Pseudomonas moraviensis M9. Cloning of lipM was based on Touchdown PCR and genome walking, and then recombinant LipM was purified by guanidine hydrochloride and the nickel-nitrilotriacetic acid resins affinity chromatography. Finally, the hydrolysis of algal oil by LipM was analyzed by gas chromatograph-mass spectrometer, thin layer chromatography and gas chromatograph. The lipM gene was first cloned from Pseudomonas moraviensis M9 via Touchdown PCR and genome walking. Sequence analysis reveals that LipM is a member of subfamily I.3 of lipases, and the predicted amino acid sequences of LipM has 82 % identity to lipase LipT from Pseudomonas mandelii JR-1, and 54 % identity to lipase PML from Pseudomonas sp. MIS38 and lipase Lip I.3 from Pseudomonas sp. CR-611. LipM was expressed in Escherichia coli, purified from inclusion bodies, and further biochemically characterized. Purified LipM differed significantly from previously reported subfamily I.3 lipases, and was eurythermic between 10 °C-95 °C. LipM activity was enhanced by Ca(2+), Sr(2+), Mn(2+), and Ba(2+), but sharply inhibited by Cu(2+), Zn(2+), Co(2+), Ni(2+), and EDTA. Compared with other lipases, LipM exhibited medium tolerance to methanol, ethanol, and isopropanol. When applied for hydrolysis of algal oil, LipM could enrich 65.88 % polyunsaturated fatty acids, which include 1.25 % eicosapentaenoic acid, 17.61 % docosapentaenoic acid, and 47.02 % docosahexaenoic acid with derivative glycerides containing 32.46 % diacylglycerols. A novel eurythermic I.3 subfamily lipase with high tolerance and stability was identified from Pseudomonas moraviensis and biochemically characterized. It will not only improve our understanding of subfamily I.3 lipases, but also provides an ideal biocatalyst for the enrichment of polyunsaturated fatty acids. Pseudomonas moraviensis have been investigated as a potential resource of lipases.


The clinical efficacy of leukocyte-poor platelet-rich plasma in arthroscopic rotator cuff repair: a meta-analysis of randomized controlled trials.
The efficacy of platelet-rich plasma (PRP) in the arthroscopic treatment of rotator cuff injury has been reported in the literature. However, conclusions have been inconsistent and more often related to differences in the types of PRP used. Therefore, to minimize these differences, we performed a meta-analysis of only studies investigating leukocyte-poor PRP to evaluate whether PRP promotes and improves the effects of arthroscopic rotator cuff repair. A comprehensive search of the PubMed, Embase, and Cochrane Library databases was conducted to evaluate the efficacy of leukocyte-poor PRP in arthroscopic rotator cuff repair. The available data were extracted, and the methodologic quality of the included studies was evaluated by the Cochrane risk-of-bias assessment tool. In total, 10 randomized controlled trials involving 742 patients were included. The results of the meta-analysis showed that treatment with leukocyte-poor PRP performed better than the control treatment in relieving postoperative pain in the short-term (mean difference [MD], -0.57; 95% confidence interval [CI], -0.79 to -0.35; P < .0001) and medium- and long-term (MD, -0.18; 95% CI, -0.34 to -0.03; P = .02) follow-up groups. However, the changes in the MD in the visual analog scale score were below the minimal clinically important difference. Regarding the Constant shoulder (MD, 3.35; 95% CI, 1.68-5.02; P < .0001) and University of California, Los Angeles (MD, 1.73; 95% CI, 0.94-2.52; P < .0001) scores, statistically significant differences were found in favor of leukocyte-poor PRP over the control treatment. However, the changes in the MD in both the Constant and University of California, Los Angeles scores were below the minimal clinically important difference. Moreover, during medium- and long-term follow-up, the retear rate in the leukocyte-poor PRP group was lower than that in the control group regardless of the rotator cuff tear size (small and medium [<3 cm] [risk ratio (RR), 0.64; 95% CI, 0.43-0.97; P = .03] vs. medium and large [>3 cm] [RR, 0.51; 95% CI, 0.34-0.77; P = .001]) and surgical repair method (single-row repair [RR, 0.61; 95% CI, 0.43-0.87; P = .007] vs. double-row suture bridge repair [RR, 0.57; 95% CI, 0.38-0.84; P = .005]). According to our study, leukocyte-poor PRP can significantly reduce the postoperative retear rate in the medium and long term regardless of the tear size and the method used for rotator cuff repair. However, the use of leukocyte-poor PRP failed to show clinically meaningful effects in terms of postoperative pain and patient-reported outcomes.


Protective effect of glucan against experimentally induced staphylococcal mastitis in ewes.
Glucan, an immunostimulant, was evaluated for its ability to modify a staphylococcal mammary challenge in ewes. Glucan was administered subcutaneously to ewes prior to lactation or during lactation, and all ewes, including a control group, were subsequently challenged intramammarily with Staphylococcus haemolyticus 40 days after the mean lambing date. The glucan treatment was shown to modify the staphylococcal mammary infection as the milk bacterial counts from all of the glucan-treated groups were significantly reduced compared to controls. For the glucan-treated groups, the highest mean somatic cell counts were recorded 1 day post-challenge, while for the control group, the mean cell count rose more gradually to peak by 3 days post-challenge. Glucan did not increase serum lysozyme levels or blood neutrophil bactericidal activity. However, there was a negative correlation between the bactericidal activity of blood neutrophils collected from the glucan-treated ewes prior to challenge and their mean milk bacterial counts post-challenge. Glucan was observed to stimulate ovine mammary macrophages in vitro, while the addition of zymosan or opsonised killed Staphylococcus aureus to macrophage cultures had no effect. These studies indicate that, in sheep, glucan can enhance some elements of the immune system against staphylococcal infections.


Structure of a T = 1 aggregate of alfalfa mosaic virus coat protein seen at 4.5 A resolution.
A T = 1 empty aggregate of alfalfa mosaic virus coat protein had been crystallized in a hexagonal unit cell and its orientation was determined with the rotation function. A single heavy-atom derivative has now been prepared and the position of the two Hg atoms per protein subunit were determined using a systematic Patterson search procedure, given the particle orientation. Phases, initially determined by single isomorphous replacement, were refined by six cycles of electron density averaging and solvent leveling to produce a 4.5 A resolution electron density map. The protein coat is confined between 95 and 58 A radius. The subunit boundary could be delineated easily. It has a central cavity reminiscent of the beta-barrel in other spherical plant viruses, but its topology could not be determined unambiguously. The spherical particle has large holes at the 5-fold axes, consistent with previous observations. The subunits have substantial interactions at the 2 and 3-fold axes. The structure of the elongated particles is discussed in relation to these results.


Left axillary incision (minithoracotomy) for PDA division.
From 1955 to 1975, 417 patent ductus arteriosus (PDA) operations were performed at Sapporo Medical University. The last 118 operations (28.3%) were done by division through the left axillary incision without mortality. Forty patients were less than 2 years old and 14 were less than 1 year old. The ratio of girls to boys was 3.5:1. Because the majority of patients with PDA are girls, parents commonly show considerable concern over the size of the operative scar. Our clinical experience demonstrates clearly the feasibility and safety of an axillary incision in dividing a PDA, even in premature infants. A minithoracotomy through the axilla is recommmended.


Descriptive Epidemiology of Gradual Return to Work for Workers With a Work-Acquired Musculoskeletal Disorder in British Columbia, Canada.
This study investigates the injury, socio-demographic, workplace, and temporal characteristics related with gradual return to work (RTW) among workers with a work-acquired musculoskeletal disorder in British Columbia, Canada. Accepted workers' compensation lost-time claims were extracted between 2010 and 2015 (n = 141,490). A multivariable logistic regression model was used to analyze the determinants of Gradual RTW. Within 1 year after injury, 41.0% of workers had at least 1 day of Gradual RTW. Serious injury severity, female sex, increasing age, wage, and firm size, longer sickness absence, and recent previous claims increased the proportion of workers being provided with Gradual RTW. Consideration of injury, socio-demographic, workplace, and temporal variability in the provision of Gradual RTW can identify inequalities in the provision and increase effective use of Gradual RTW for workers with musculoskeletal disorders.


Atrial pacing: intracardiac conduction assessed by his bundle electrograms acquired from the permanent atrial electrode at implantation.
His bundle electrograms were recorded from conventional J-shaped atrial electrodes at implantation in twelve consecutive patients who had sinus node disorder. Five patients with impairment of atrioventricular conduction, received atrioventricular (DVI) pacemakers. His bundle recording by this method is simple and reliable, avoids the discomfort of the conventional technique, and represents a new application for the well established atrial "J" electrode.


Adenosine A2A receptor activation is determinant for BDNF actions upon GABA and glutamate release from rat hippocampal synaptosomes.
Adenosine, through A(2A) receptor (A(2A)R) activation, can act as a metamodulator, controlling the actions of other modulators, as brain-derived neurotrophic factor (BDNF). Most of the metamodulatory actions of adenosine in the hippocampus have been evaluated in excitatory synapses. However, adenosine and BDNF can also influence GABAergic transmission. We thus evaluated the role of A(2A)R on the modulatory effect of BDNF upon glutamate and GABA release from isolated hippocampal nerve terminals (synaptosomes). BDNF (30 ng/ml) enhanced K(+)-evoked [(3)H]glutamate release and inhibited the K(+)-evoked [(3)H]GABA release from synaptosomes. The effect of BDNF on both glutamate and GABA release requires tonic activation of adenosine A(2A)R since for both neurotransmitters, the BDNF action was blocked by the A(2A)R antagonist SCH 58261 (50 nM). In the presence of the A(2A)R agonist, CGS21680 (30 nM), the effect of BDNF on either glutamate or GABA release was, however, not potentiated. It is concluded that both the inhibitory actions of BDNF on GABA release as well as the facilitatory action of the neurotrophin on glutamate release are dependent on the activation of adenosine A(2A)R by endogenous adenosine. However, these actions could not be further enhanced by exogenous activation of A(2A)R.


Combining general and central measures of adiposity to identify risk of hypertension: a cross-sectional survey in rural India.
In three socioeconomically diverse regions of rural India, we determined the optimal cut-offs for definition of overweight, the prevalence of overweight, and the relationships between measures of overweight and risk of hypertension. Villages were randomly sampled within rural Trivandrum, West Godavari, and Rishi Valley. Sampling of individuals was stratified by age group and sex. Cut-offs for measures of adiposity were compared using area under the receiver operating characteristic curve. Associations between hypertension and definitions of overweight were assessed by logistic regression. Of 11 657 participants (50 % male; median age 45 years), 29.8 % had hypertension. Large proportions were overweight as defined by body mass index (BMI) ≥ 23 kg/m2 (47.7 %), waist circumference (WC) ≥ 90 cm for men or ≥ 80 cm for women (39.6 %), waist-hip ratio (WHR) ≥ 0.9 for men or ≥ 0.8 for women (65.6 %), waist-height ratio (WHtR) ≥ 0.5 (62.5 %), or by BMI plus either WHR, WC or WHtR (45.0 %). All definitions of overweight were associated with hypertension, with optimal cut-offs being at, or close to, the World Health Organization (WHO) Asia-Pacific standards. Having overweight according to both BMI and a measure of central adiposity was associated with approximately twice the risk of hypertension than overweight defined by only one measure. Overweight, as assessed by both general and central measures, is prevalent in rural southern India. WHO standard cut-offs are appropriate in this setting for assessing risk of hypertension. However, combining BMI with a measure of central adiposity identifies risk of hypertension better than any single measure. The risk of hypertension is significantly greater in those centrally and generally overweight than those overweight by a single measure.


The spatial and temporal distribution of heavy metals in sediments of Victoria Harbour, Hong Kong.
Victoria Harbour has received substantial loadings of pollutants from industrial and municipal wastewater discharged since the 1950s. Inputs of contaminants have declined dramatically during the last two decades as a result of better controls at the source and improved wastewater treatment facilities. To assess the spatial and temporal changes of metal contaminants in sediments in Victoria Harbour, core and grab sediments were collected. The central harbour areas were generally contaminated with heavy metals. The spatial distribution of trace metals can probably be attributed to the proximity of major urban and industrial discharge points, and to the effect of tidal flushing in the harbour. In the sediment cores, the highest concentrations of trace metals were observed to have accumulated during the 1950s-1980s, corresponding with the period of rapid urban and industrial development in Hong Kong. From the late 1980s, there has been a major decline in the concentrations of trace metals, due to a reduction in industrial activities and to the enactment of wastewater pollution controls in the territory. The Pb isotopic compositions of the sediments revealed the anthropogenic inputs of Pb to the harbour. The (206)Pb/(207)Pb ratios varied from 1.154 to 1.190, which were lower than those of background geological materials in Hong Kong ((206)Pb/(207)Pb: 1.201-1.279). The data also indicated that the Pb in the harbour sediments most likely originated from mixed sources, including the leaded gasoline used in the past and other anthropogenic sources.


Spontaneous correction of angular fracture deformity in the rat.
The different parts of long bone are known to participate in the spontaneous correction of fracture deformity. However, the relative contribution of growth plate, epiphysis and diaphysis of bone during the correction process is not clear. We used a rat model of tibial fracture fixed with a semi-rigid intramedullary pin in anterior angulation, and evaluated the magnitude, temporal course and pertinent sites of spontaneous deformity correction by means of radiography and bone mineral uptake. Over a 12-week period, the mean angular deformity was corrected from 27 degrees to 11 degrees. The major portion of the correction (14 degrees of 16 degrees) occurred within 3 weeks, concomitantly with fracture healing. The angle of the proximal growth plate changed 8 degrees over the study period. The first 3 weeks were characterized by intense bone formation on the concave side of the fracture. From weeks 3-8, signs of resorption predominated on the corresponding convex side. On the concave side, the front of new bone formation in the proximal diaphysis moved in the opposite direction to that at the fracture level, so that both sites contributed to deformity correction. We found that different sites of a diaphyseal bone fractured in angulation respond quite differently, but still in an orchestrated way to promote correction by modeling. Notably, most of the spontaneous correction occurred during the reparative phase, the major contributor being the diaphysis, not the growth plate. Compared to other reports on angulated fracture using rigid fixation and limb immobilization, our data suggest that semi-rigid fixation and early weight bearing is more efficient in enhancing not only healing, but also deformity correction.