The experimental infection of horses with Murray Valley encephalitis and Ross River viruses.
Eleven weanling horses were inoculated with Murray Valley encephalitis and Ross River viruses either by intravenous injection or by the bite of Culex annulirostris or Aedes vigilax mosquitoes infected orally. Five of the 11 horses circulated trace amounts of MVE virus for 1 to 5d and they infected 7/408 Cx annulirostris which subsequently fed on them. Haemagglutination-inhibiting antibody persisted at detectable levels for the 24-week observation period. With Ross River virus, only one of 11 horses inoculated developed a viraemia detectable by inoculation of suckling mice but 5 horses contained virus sufficient to infect 41/383 Cx annulirostris that fed on them 3 to 4 days after inoculation. On primary inoculation with Ross River virus, only 2 horses developed HI antibody but late responses occurred in 3 horses following probable naturally acquired re-infections. With both viruses, most horses remained normal, some developed mild pyrexia and transient clinical signs. This paper, therefore, indicates that horses are unlikely to be efficient amplifiers of either MVE or RR viruses and does little to incriminate them as important pathogens.


Comorbid infections induce progression of visceral leishmaniasis.
Visceral leishmaniasis (VL) is a vector borne zoonotic disease endemic in humans and dogs in Brazil. Due to the increased risk of human infection secondary to the presence of infected dogs, public health measures in Brazil mandate testing and culling of infected dogs. Despite this important relationship between human and canine infection, little is known about what makes the dog reservoir progress to clinical illness, significantly tied to infectiousness to sand flies. Dogs in endemic areas of Brazil are exposed to many tick-borne pathogens, which are likely to alter the immune environment and thus control of L. infantum. A cross-sectional study of 223 dogs from an area of Natal, in the Rio Grande do Norte, Brazil, were studied to determine the association between comorbid tick-borne disease and Leishmania infection in this endemic area. The risk of Leishmania seropositivity was 1.68× greater in dogs with tick-borne disease seropositivity compared to those without (Adjusted RR: 1.68, 95% CI: 1.09-2.61, P = 0.019). A longitudinal study of 214 hunting dogs in the USA was conducted to determine the causal relationship between infection with tick-borne diseases and progression of VL. Hunting dogs were evaluated three times across a full tick season to detect incident infection with tick-borne diseases. A logistic regression model with generalized estimating equations to estimate the parameters was used to determine how exposure to tick-borne disease altered VL progression over these three time points when controlling for other variables. Dogs infected with three or more tick-borne diseases were 11× more likely to be associated with progression to clinical VL than dogs with no tick-borne disease (Adjusted RR: 11.64, 95% CI: 1.22-110.99, P = 0.03). Dogs with exposure to both Leishmania spp. and tick-borne diseases were five times more likely to die during the study period (RR: 4.85, 95% CI: 1.65-14.24, P = 0.0051). Comorbid tick-borne diseases dramatically increased the likelihood that a dog had clinical L. infantum infection, making them more likely to transmit infection to sand flies and people. As an important consequence, reduction of tick-borne disease exposure through topical or oral insecticides may be an important way to reduce progression and transmissibility of Leishmania infection from the canine reservoir to people.


Efficacy of Naltrexone for the Treatment of Alcohol Dependence in Latino Populations.
Naltrexone has been identified as a promising psychopharmacological treatment for alcohol dependence. Previous studies have suggested that its efficacy may vary based on ethnic background. The current study examined the efficacy of naltrexone in the treatment of alcohol dependence in Latino adults, a previously unexplored population. This was a secondary analysis of the Combined Pharmacotherapies and Behavioral Interventions for Alcohol Dependence (COMBINE) Study. The overall COMBINE sample consisted of 1,383 adult participants who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria for alcohol dependence, including 155 Latinos, who are the focus of this report. Consistent with the main trial, primary drinking outcomes, including percentage of days abstinent (PDA) and time to first heavy drinking day (TTHD), were examined. In addition, we examined the effects of naltrexone on a clinically relevant secondary outcome measure, global clinical outcome of alcohol consumption and alcohol-related problems. As seen with the subsample of African Americans from the COMBINE Study, results of the present analysis indicated that there were no significant effects of naltrexone on PDA and TTHD despite these significant effects in the original study. However, contrary to findings in the African American subsample, for Latino participants naltrexone was a significant predictor of a good global clinical outcome (i.e., abstinence or moderate drinking without problems). Naltrexone was not significantly associated with improvements in the primary drinking outcomes of PDA or TTHD at the end of treatment or at follow-up. However, Latinos appeared to benefit from naltrexone as demonstrated by improved ratings of global clinical outcome. These results indicate mixed findings for the efficacy of naltrexone among Latinos in the COMBINE Study.


Robust expression of vault RNAs induced by influenza A virus plays a critical role in suppression of PKR-mediated innate immunity.
Protein kinase R (PKR) is a vital component of host innate immunity against viral infection. However, the mechanism underlying inactivation of PKR by influenza A virus (IAV) remains elusive. Here, we found that vault RNAs (vtRNAs) were greatly induced in A549 cells and mouse lungs after infection with IAV. The viral NS1 protein was shown to be the inducer triggering the upregulation of vtRNAs. Importantly, silencing vtRNA in A549 cells significantly inhibited IAV replication, whereas overexpression of vtRNAs markedly promoted the viral replication. Furthermore, in vivo studies showed that disrupting vtRNA expression in mice significantly decreased IAV replication in infected lungs. The vtRNA knockdown animals exhibited significantly enhanced resistance to IAV infection, as evidenced by attenuated acute lung injury and spleen atrophy and consequently increased survival rates. Interestingly, vtRNAs promoted viral replication through repressing the activation of PKR and the subsequent antiviral interferon response. In addition, increased expression of vtRNAs was required for efficient suppression of PKR by NS1 during IAV infection. Moreover, vtRNAs were also significantly upregulated by infections of several other viruses and involved in the inactivation of PKR signaling by these viruses. These results reveal a novel mechanism by which some viruses circumvent PKR-mediated innate immunity.


Promotion of a community culture in nursing research.
This article focuses on local practice-based research and development. It uses examples from both nursing practice and education to explore some factors that prevent, promote and influence the establishment of a research culture in clinical nursing. The article presents potential approaches for successful practitioner-led and clinical/academic research initiatives, explored through practice development and communities of practice. It also highlights the challenges of these approaches.


Bowman lecture. Current concepts of infantile esotropia.
Several forms of esotropia with a different pathophysiology that meet the criterion of an onset early in life must be distinguished from essential infantile esotropia. A hypothesis is presented, according to which a delayed development or a congenital defect of retinal disparity sensitivity (motor fusion) in an otherwise normal infant with immature sensory functions causes esotropia under the influence of various strabismogenic factors. Some of these factors are genetically determined, hence the familial occurrence of essential infantile esotropia. The absence or marked decrease of stereopsis and the asymmetry of optokinetic nystagmus are interpreted as the consequence of ocular misalignment early in life rather than of structural anomalies in the afferent visual pathways of esotropic patients. The therapeutic results after surgery are classified into four groups: subnormal binocular vision, microtropia, small angle eso- or exotropia and large angle residual or consecutive eso- or exodeviations. Analysis of data from 358 operated patients with a documented onset of esotropia prior to the sixth month of life has shown that the probability of obtaining an optimal functional result is increased when surgical alignment is completed before completion of the second year of life. However, surgery after the age of two or even four years of life does not preclude the development of binocular vision on a subnormal or anomalous basis.


Identifying abuse in older people.
This article provides a broad overview of the issues relating to the abuse of older people. Information is included to help nurses identify suspected cases of abuse and guidance on how to manage these situations is provided.


Carbon flux assessment in cow-calf grazing systems.
Greenhouse gas (GHG) fluxes and soil organic carbon (SOC) accumulation in grassland ecosystems are intimately linked to grazing management. This study assessed the carbon equivalent flux (Ceq) from 1) an irrigated, heavily stocked, low-density grazing system, 2) a nonirrigated, lightly stocked, high-density grazing system, and 3) a grazing-exclusion pasture site on the basis of the GHG emissions from pasture soils and enteric methane emissions from cows grazing different pasture treatments. Soil organic carbon and total soil nitrogen stocks were measured but not included in Ceq determination because of study duration and time needed to observe a change in soil composition. Light- and heavy-stocking systems had 36% and 43% greater Ceq than nongrazed pasture sites, respectively ( < 0.01). The largest contributor to increased Ceq from grazing systems was enteric CH emissions, which represented 15% and 32% of the overall emissions for lightly and heavily stocked grazing systems, respectively. Across years, grazing systems also had increased nitrous oxide (N2O; < 0.01) and CH emissions from pasture soils ( < 0.01) compared with nongrazed pasture sites but, overall, minimally contributed to total emissions. Results indicate no clear difference in Ceqflux between the grazing systems studied when SOC change is not incorporated ( = 0.11). A greater stocking rate potentially increased total SOC stock ( = 0.02), the addition of SOC deeper into the soil horizon ( = 0.01), and soil OM content to 30 cm ( < 0.01). The incorporation of long-term annual carbon sequestration into the determination of Ceq could change results and possibly differentiate the grazing systems studied.


Immune Cell Landscaping Reveals Distinct Immune Signatures of Inflammatory Bowel Disease.
Determining how the profile of immune cells varies with their disease subtypes and across lesion locations is critical for understanding the pathogenesis in inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC). To that end, we herein combined the IBD TaMMA framework and the CIBERSORT pipeline to deconvolute the large amount of RNA-seq data from patients with IBD (both CD and UC were included) and healthy human controls across 28 cohorts (a total of 3,852 samples) while accommodating data heterogeneity across cohorts, to define the immune cell landscape of IBD. Our study uncovered that both absolute quantities of innate and adaptive immune cell populations were elevated in most intestinal regions of IBD patients, yet disease-specific (CD versus UC) and intestinal location (ileum, colon, and rectum)-specific features. In the ileum, the increase in innate immune cells was more pronounced in CD than UC. In contrast, innate and adaptive immune cells were elevated more drastically in the UC than CD in the rectum. Such revelation of immune signatures across the highly variable IBD phenotypes (in both disease subtypes and intestinal regions) underpins differential immune-pathophysiological mechanisms in IBD pathogenesis and therefore serves as a resource for the development of future targeted studies.


Multiple metrics quantify and differentiate responses of vegetation to composition B.
Quantifying vegetation response to explosive compounds has focused predominantly on morphological impacts and uptake efficiency. A more comprehensive understanding of the total impacts of explosives on vegetation can be gained using a multivariate approach. We hypothesized that multiple variables representing morphological and physiological responses will more clearly differentiate species and treatments than any single variable. Individuals of three plant species were placed in soils contaminated with Composition B, which comprises 60% hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) and 40% 2,4,6-trinitrotoluene (TNT), and grown for 2 months. Response metrics used included photosynthetic operation, water relations, growth characteristics, as well as nitrogen and carbon concentrations and isotopic compositions. Individual metrics showed high variability in response across the three species tested. Water relations and nitrogen isotopic composition exhibited the most consistent response across species. By comparing multiple variables simultaneously, better separation of both species and exposure was observed. The inclusion of novel metrics can reinforce previously established concepts and provide a new perspective. Additionally, the inclusion of various other metrics can greatly increase the ability to identify and differentiate particular groups. By using multivariate analyses and standard vegetation metrics, new aspects of the vegetation response to explosive compounds can be identified.


Role of Acid-Base Equilibria in the Size, Shape, and Phase Control of Cesium Lead Bromide Nanocrystals.
A binary ligand system composed of aliphatic carboxylic acids and primary amines of various chain lengths is commonly employed in diverse synthesis methods for CsPbBr3 nanocrystals (NCs). In this work, we have carried out a systematic study examining how the concentration of ligands (oleylamine and oleic acid) and the resulting acidity (or basicity) affects the hot-injection synthesis of CsPbBr3 NCs. We devise a general synthesis scheme for cesium lead bromide NCs which allows control over size, size distribution, shape, and phase (CsPbBr3 or Cs4PbBr6) by combining key insights on the acid-base interactions that rule this ligand system. Furthermore, our findings shed light upon the solubility of PbBr2 in this binary ligand system, and plausible mechanisms are suggested in order to understand the ligand-mediated phase control and structural stability of CsPbBr3 NCs.


Splanchnic vein thrombosis associated with SARS-CoV-2 infection: A VALDIG case-control study.
Whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is a risk factor for splanchnic vein thrombosis (SVT) is unknown. This study aims to assess the impact of SARS-CoV-2 infection on the presentation and prognosis of recent SVT and to identify specific characteristics of SARS-CoV-2-associated SVT. This is a retrospective study collecting health-related data of 27 patients presenting with recent SVT in the context of SARS-CoV-2 infection in 12 Vascular Liver Disease Group (VALDIG) centres and in comparison with 494 patients with recent SVT before the SARS-CoV-2 pandemic. Twenty-one patients with SARS-CoV-2 had portal vein thrombosis with or without thrombosis of another splanchnic vein, two had superior mesenteric vein thrombosis, one had splenic vein thrombosis, and three had hepatic vein thrombosis. Diagnosis of SVT was made 10 days (95% CI 0-24 days) after the diagnosis of SARS-CoV-2 infection. Fever (52 vs. 15%; p <0.001) and respiratory symptoms (44 vs. 0%; p <0.001) were more frequent, and median lymphocyte count was lower (1.1 × 103/mm3vs. 1.6 × 103/mm3; p = 0.043) in patients with infection than in those without SARS-CoV-2 infection. A prothrombotic condition was identified in 44 and 52% of patients with and without SARS-CoV-2 infection, respectively (p = 0.5). All patients with SARS-CoV-2 received anticoagulation therapy. During a median follow-up of 250 days, three SARS-CoV-2-infected patients (11%) required intestinal resection for infarction 1 to 3 months after diagnosis of SVT compared with 13 (2.6%) controls (p = 0.044). Partial or complete recanalisation of the thrombosed splanchnic vein was performed in 33% of patients with SARS-CoV-2. SARS-CoV-2 infection can be associated with recent SVT. Intestinal infarction leading to intestinal resection might be more frequent in patients with SARS-CoV-2. SARS-CoV-2 infection can be associated with recent SVT. SVT occurring during SARS-CoV-2 infection is characterised by a higher frequency of respiratory symptoms and a lower lymphocyte count. Intestinal infarction leading to intestinal resection appears to occur more frequently in patients with SARS-CoV-2.


Photoaffinity labeling the substance P receptor using a derivative of substance P containing p-benzoylphenylalanine.
A novel photoreactive substance P (SP) analogue has been synthesized by solid-phase peptide synthesis methodology to incorporate the amino acid p-benzoyl-L-phenylalanine [L-Phe(pBz)] in place of the Phe8 residue of SP. [Phe8(pBz)]SP was equipotent with SP in competing for SP binding sites on rat submaxillary gland membranes and had potent sialagogic activity in vivo. In the absence of light, the 125I-labeled Bolton-Hunter conjugate of [Phe8(pBz)]SP bound in a saturable and reversible manner to an apparently homogeneous class of binding sites (Bmax = 0.2 pmol/mg of membrane protein) with an affinity KD = 0.4 nM. The binding of 125I-[Phe8(pBz)]SP was inhibited competitively by various tachykinin peptides and analogues with the appropriate specificity for SP/NK-1 receptors. Upon photolysis, up to 70% of the specifically bound 125I-[Phe8(pBz)]SP underwent covalent linkage to two polypeptides of Mr = 53,000 and 46,000, identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography. Quantitative analysis of the inhibitory effects of SP and related peptides on 125I-[Phe8(pBz)]SP photoincorporation indicated that the binding sites of the two photolabeled polypeptides have the same peptide specificity, namely, that typical of NK-1-type SP receptors. In addition, the labeling of the two polypeptides was equally sensitive to inhibition by guanyl-5'-yl imidodiphosphate, a nonhydrolyzable analogue of GTP. Further information on the relationship between the two labeled SP binding sites was provided by enzymatic digestion studies: the Mr = 46,000 polypeptide contains N-linked carbohydrates and is derived most likely from the higher molecular weight species by proteolytic nicking.(ABSTRACT TRUNCATED AT 250 WORDS)


Saphenous vein graft pseudoaneurysm: a case for medical management.
Saphenous vein bypass pseudoaneurysm is rare but fatal complication after coronary bypass surgery. Pseudoaneurysm is managed either with a surgical or percutaneous approach. This patient underwent quadruple coronary artery bypass grafting 10 years earlier and was referred for recurrence of angina. Coronary and graft angiography revealed a pseudoaneurysm in the saphenous vein graft supplying the intermediate coronary artery. After discussion with the cardiothoracic surgeons, the patient was managed conservatively. He was continued on Aspirin, beta-blockers, statins, nitrates and angiotensin converting enzyme inhibitors. He was followed-up regularly in outpatient clinic with a planned repeat coronary and graft angiography. The patient's symptoms remain stable and repeat angiography 24 months later did not show any significant deterioration of the graft pseudoaneurysm. He remains stable at 12 months after the repeated angiography.


Generation of all-male-like sterile zebrafish by eliminating primordial germ cells at early development.
Production of all-male and sterile fish may not only substantially improve yield but also be crucial for the application of genome modified species in aquaculture. Previously, it was reported that the fish lacking primordial germ cells (PGCs) becomes infertile, and nitroreductase, an enzyme converting non-toxic metronidazole (MTZ) into toxic metabolites, induces targeted toxicity to kill the cells expressing it. In this study, we generated a transgenic zebrafish line of Tg(nanos3:nfsB-mCherry-nanos3 3'UTR) in which the NfsB nitroreductase is solely expressed in PGCs. Treating the embryos derived from the female transgenic zebrafish with MTZ from 0 through 2 dpf (days post fertilization), we found that the germ cells were completely eliminated in the ones older than 2.5 dpf. At 20 dpf, the MTZ-treated juvenile had no germ cells in their gonads. At 100 dpf, the MTZ-treated adult exhibited male-like morphology and showed normal mating behaviors although they had no germ cells but only supporting cells in their gonads. Taken together, our results demonstrated that conditional elimination of PGCs during early development make the zebrafish male-like and infertile. It may provide an alternative strategy to make sterile and all-male farmed fish that is good for increasing aquaculture yield and preventing the genome modified species from potential ecological risks.


UHRF1 promotes breast cancer progression by suppressing KLF17 expression by hypermethylating its promoter.
UHRF1 is an epigenetic regulator and perform pivotal functions in cell tumorigenesis. We found UHRF1 is increased in breast cancer and patients with high UHRF1 levels have poorer prognoses than those with low UHRF1 levels. However, the underlying mechanisms remain largely unknown. Here, we found overexpression UHRF1 indeed promoted cell proliferation and migration, whereas its downregulation had the opposite functions. In vivo, UHRF1 also accelerated tumor growth. Mechanistically, microarrays were performed in MDA-MB-231 sh-UHRF1 and NC cells and KLF17, with rich CpG islands on its promoter region, finally caused our attention. Then, the expression of UHRF1 and KLF17 was testified negatively correlated in breast cancer cell lines and tissues. Additionally, the inhibition of cell proliferation and migration by UHRF1 depletion can be rescued by KLF17 silencing, suggesting KLF17 is downstream gene of UHRF1. The potential mechanism is that overexpression UHRF1 increased methylation of CpG nucleotides on KLF17 promoter, while UHRF1 silence decreased methylation. Collectively, our results demonstrated that increased UHRF1 can promote breast cancer cell proliferation and migration via silencing of KLF17 expression through CpG island methylation on its promoter.


Human Factors Approach to Assess Physician Workload in Elective Plastic Surgery Breast Procedures.
Human factors research involves the study of work system interactions, physician workload, cognitive effort, and performance. This pilot study incorporated a human factor approach and other surgery-based metrics to assess cognitive workload among plastic surgeons during elective plastic surgery breast procedures. In this prospective study of plastic surgery breast procedures over a 3-month period, surgeon and patient demographics and procedural details were collected. The lead surgeon assessed each procedure using a validated workload questionnaire (National Aeronautics and Space Administration Task Load Index [NASA-TLX]) that included 6 subscales (ie, mental, physical, temporal demand, performance, effort, and frustration), a question on distraction, and their expectation of procedural difficulty. Fifty-seven cases were included in this study. Surgical duration had a positive correlation with increased mental demand (P < .001), physical demand (P < .001), and degree of distractions (P < .001). Free flap reconstruction, breast reduction, and transgender mastectomy had the highest average mental, physical demands, and perceived effort. Bilateral cases had significantly higher workload than unilateral ones (P = .002). NASA-TLX scores between immediate and delayed reconstructions were comparable, but delayed cases had higher degree of distractions (P = .04). There was a strong correlation between degree of distractions and increased mental workload (R = 0.68; P < .001), increased physical demand (P = 0.61; P < .001), and increased temporal demand (R = 0.78; P < .001). More difficult procedures were associated with greater procedural duration than those rated as difficult as expected or less difficult than expected (P = .02). These preliminary data demonstrated multiple factors that may influence and govern perceived physician workload and may provide insight for targeted quality improvement to plan procedures safely and effectively.


The effect of protein and dietary energy levels and housing regime on production and reproduction parameters of turkey hens.
Two experiments were conducted using 960 Large Board Breasted White turkey hens to measure the effect of diet and confinement housing versus range pens on egg production, fertility and hatchability. A 2 X 3 factorial arrangement of diets provided protein levels of 15 and 18% with metabolizable energy levels of 2666, 2893, and 3101 kcal. per kg. of diet. The hens were randomized into 24 range pens and 24 pens in an open-sided house. Dietary protein levels had no effect on body weight, feed consumption, egg production, fertility or hatchability. Hens fed the higher energy diet produced larger eggs (P less than .05), but there was no difference in total egg production due to dietary energy level. As dietary energy level increased, feed consumption linearly decreased. Hens fed the 3102 kcal./M.E./kg. diet had significantly higher fertility (P less than .05) than hens fed the intermediate energy level diet with no differences between the lowest energy level and either of the other two levels. Fertile eggs from hens fed the intermediate energy level diet had lower hatchability (P less than .05) than those from hens fed either the lower or higher dietary energy levels. Type of housing and no effect on average body weight or feed consumption on a hen-day basis. Housing treatment had no effect on percent fertility or hatchability. Hens housed in the range pens produced more and larger eggs (P less than .05) and more eggs per kg. of feed than hens penned in the house.


Effects of bromocriptine in Huntington chorea. Case report.
1. The effects of bromocriptine (BC) on choreiform movement were compared with those of bromperidol (BP) and fluphenazine (FLZ) in a patient with Huntington disease. The patient (male, 42 years old) was treated with BP (15 mg/day, 4 weeks), FLZ (3 mg/day, 4 weeks), low dose of BC (5 mg/day, 4 weeks) and relatively high dose of BC (10 mg/day, 8 weeks). The CSF content of homovanilic acid (HVA) was assayed at last day of the each drug trial. The efficacy of the drugs was evaluated by electromyography. 2. Although BP and FLZ did not succeed to ameliorate the choreiform movement, both low dose and high dose BC showed rapid improvement of the involuntary movement. The CSF HVA concentration was 35.0 ng/ml before beginning treatment. Whereas FLZ and high dose of BC substantially increased the levels of HVA after the dosage (49.3 and 53.1 ng/ml, respectively), moderate increase of HVA (41.5 ng/ml) was observed when the low dose of BC was administered. These observations suggest that increase of CSF HVA might be necessary for clinical improvement of choreiform movement but not correlate with the degree of improvement and dopamine agonists could be useful drug for the treatment of choreiform movement which is refractory to the administration of neuroleptics.


The development of immunity to Eimeria species in broilers given anticoccidial drugs.
The acquisition of immunity to Eimeria species was studied in broilers reared in floor-pens on new and used litter, and given different anticoccidial drug programmes. Programmes included a single drug (synthetic compound or ionophore) given in the starter and grower feed, or 'shuttle' programmes comprising a synthetic drug followed by an ionophore (or vice versa) given in the starter and grower feeds, respectively. None of the drug programmes prevented parasite multiplication, since oocysts were found in the intestines of birds and in the litter. Birds were challenged at weekly intervals with a mixture of species (E. acervulina, E. maxima and E. tenella) in order to establish whether protective immunity had developed. Birds reared on used litter that received no medication acquired immunity by 5 weeks, whereas birds reared on new litter were not fully protected against a challenge inoculum until 7 weeks of age. Apart from birds given an ionophore followed by a synthetic drug, medicated birds developed immunity by 7 weeks, irrespective of the type of drug programme, or whether they had been reared on new or used litter. Birds reared in commercial houses (where one and seven previous flocks had been raised) and given a synthetic drug followed by ionophores, also developed immunity to Eimeria species. Immunity was acquired more rapidly to E. maxima than E. acervulina or E. tenella.


Prognostic performance of early absence of pupillary light reaction after recovery of out of hospital cardiac arrest.
Loss of pupillary light reactivity (PLR) three days after a cardiorespiratory arrest is a prognostic factor. Its predictive value upon hospital admission remains unclear. Our objective was to determine the prognostic value of the absence of PLR upon hospital admission in patients with out-of-hospital cardiac arrest. We prospectively included all out-of-hospital cardiac arrests occurring between July 2011 and July 2017 treated by a mobile medical team (MMT) based on data from a French cardiac arrest registry database. PLR was evaluated upon hospital admission and the outcome on day 30. The prognosis was classified as good for Cerebral Performance Category (CPC) 1 or 2, and poor for CPC 3-5 or in case of death. Data from 10151 patients was analysed. The sensitivity and specificity of the absence of PLR for a poor outcome were 72.2% (71.2-73.2) and 68.8% (66.7-70.1), respectively. We identified several variables modifying the sensitivity values and the false positive fraction of a factor, ranging from 0.49 (0.35-0.69) for the Glasgow Coma Scale to 2.17 (1.09-2.48) for pupillary asymmetry. Among those living with CPC 1 or 2 on day 30 (n = 1990; 19.6%), 621 (31.2% (29.2-33.3)) had no PLR upon hospital admission. In the multivariate analysis, loss of PLR was associated with a poor outcome (OR = 3.1 (2.7-3.5)). Loss of pupillary light reactivity upon hospital admission is predictive of a poor outcome after out-of-hospital cardiac arrest. However, it does not have sufficient accuracy to determine prognosis and decision making.


Motivation, stress, anxiety, and cortisol responses in elite paragliders.
In this study metamotivational dominance (measured with the Telic Dominance Scale), precompetition anxiety (evaluated with the CSAI-2), perceived stress (measured with the Perceived Stress Scale), and cortisol responses by 10 paragliding competitors prior to and following a paragliding competition were examined. Saliva was collected for each subject for cortisol analysis on eight occasions: during a resting day (baseline values) and prior to and after competition. Analysis indicated subjects were all paratelic-dominant (characterized by a desire for high arousal, a focus on the present). Scores were high on the Perceived Stress Scale and cognitive nxiety (a telic emotion). Cortisol values showed a significant increase early on the day of the competition and remained elevated all the day, with highest concentrations at the start. Participants' cognitive anxiety and cortisol responses were significantly correlated .79 just before the jump and the direction of the cognitive anxiety was rated as facilitative of performance. These results may suggest that the more frequently the subject is playful in life, the more cortisol they produce when aroused in a less frequent telic state.


Competition of spin fluctuations and phonons in superconductivity of ZrZn(2).
It has long been suspected that spin fluctuations in ZrZn2 may lead to a triplet superconductivity. We point out another possibility, an inhomogeneous singlet (Fulde-Ferrell) state. We calculated the electronic structure, as well as the zone center phonons and their coupling with electrons. We find that the exchange splitting is nonuniform and the Fermi surface exhibits substantial nesting. Both factors favor a Fulde-Ferrell state at parts of the Fermi surface. We find a substantial coupling of Zr rattling modes with electrons, which can provide the necessary pairing in the s-channel.


Schizosaccharomyces pombe glycosylation mutant with altered cell surface properties.
Mutagenesis of Schizosaccharomyces pombe cells yielded a strain that made reduced amounts of invertase. A comparison of the O- and N-linked carbohydrate chains of the wild-type and mutant glycoproteins revealed that a single type of alpha 1-->2-linked mannose was missing in the mutant. Analysis of the wild-type galactomannoprotein showed that it contained a heterogeneous small "core" oligosaccharide fraction linked to asparagine with sugar compositions that ranged from Man9(GlcNAc)2- to Gal4Man10(GlcNAc)2-. The galactose units are in terminal positions of a Man10(GlcNAc)2- unit that is similar to the mannoprotein core of Saccharomyces cerevisiae. Attached to this core in a larger oligosaccharide fraction is an alpha 1-->6-linked polymannose chain that is substituted at position 2 with alpha-linked mannose and galactose. The O-linked sugars consist of mannose, alpha 1-->2-linked mannosylmannose and alpha 1-->2-linked galactosylmannose, along with small amounts of tri- and tetrasaccharides. The glycosylation mutant lacks alpha 1-->2-linked mannose on both the O-linked chains and the outer chain of the large N-linked chains, suggesting that it may be defective in regulation of an alpha 1,2-mannosyltransferase that adds mannose to glycoproteins in the Golgi.


Posttranslational modifications of lysine and evolving role in heart pathologies-recent developments.
The alteration in proteome composition induced by environmental changes and various pathologies is accompanied by the modifications of proteins by specific cotranslational and PTMs. The type and site stoichiometry of PTMs can affect protein functions, alter cell signaling, and can have acute and chronic effects. The particular interest is drawn to those amino acid residues that can undergo several different PTMs. We hypothesize that these selected amino acid residues are biologically rare and act within the cell as molecular switches. There are, at least, 12 various lysine modifications currently known, several of them have been shown to be competitive and they influence the ability of a particular lysine to be modified by a different PTM. In this review, we discuss the PTMs that occur on lysine, specifically neddylation and sumoylation, and the proteomic approaches that can be applied for the identification and quantification of these PTMs. Of interest are the emerging roles for these modifications in heart disease and what can be inferred from work in other cell types and organs.


Moving the patient in bed: effects on intracranial pressure.
Intracranial pressure (ICP) was measured in 20 patients before and after each of eight nursing care activities: turning the body to four positions, passive range of motion (arm extension and hip flexion), and rotation of the head to the right and to the left. Technically usable data was available for 18 patients. Mean ICP increased for at least five minutes in all patients after one of the four turns and in 88 percent after half the turns. Change in mean ICP with one of a pair of lateral or supine turns was strongly predictive of the direction of change (increase or decrease) of the other turn of the pair. Large increases in ICP occurred in the five patients for whom head rotation was done, while there was minimal change in ICP with both passive range of motion procedures. A cumulative increase in ICP occurred with activities spaced 15 minutes apart, regardless of the nature of the activity. No cumulative increase in ICP was found with procedures spaced at least one hour apart.


Development of a Radiolabeled Peptide-Based Probe Targeting MT1-MMP for Breast Cancer Detection.
Breast cancer is one of the most frequent and aggressive primary tumors among women of all races. Matrix metalloproteinase (MMPs), a family of zinc- and calcium-dependent secreted or membrane anchored endopeptidases, is overexpressed in varieties of diseases including breast cancer. Therefore, noninvasive visualization and quantification of MMP in vivo are of great interest in basic research and clinical application for breast cancer early diagnosis. Herein, we developed a 99mTc labeled membrane type I matrix metalloproteinase (MT1-MMP) specific binding peptide, [99mTc]-(HYNIC-AF7p)(tricine)(TPPTS), for in vivo detection of MDA-MB-231 breast tumor by single photon emission computed tomography (SPECT). [99mTc]-(HYNIC-AF7p)(tricine)(TPPTS) demonstrated nice biostability and high MT1-MMP binding affinity in vitro and in vivo. Tumor-to-muscle ratio was found to reach to the highest (4.17±0.49) at 2 hour after intravenously administration of [99mTc]-(HYNIC-AF7P)(tricine)(TPPTS) into MDA-MB-231 tumor bearing mice. Overall, [99mTc]-(HYNIC-AF7P)(tricine)(TPPTS) demonstrated great potential for MT1-MMP targeted detection in vivo and it would be a promising molecular imaging probe that are probably beneficial to breast cancer early diagnoses.


Dual-wavelength long-pulsed 755-nm alexandrite/1,064-nm Nd:YAG laser versus Nd:YAG alone for treatment of palmoplantar verruca.
We compared the effectiveness and safety of the long-pulsed neodymium-doped yttrium-aluminum-garnet (Nd:YAG) laser alone and combined with a 755-nm alexandrite laser for treating palmoplantar warts. We divided patients into two groups to receive up to four monthly treatments with Nd:YAG alone (single-wavelength) or combined with the alexandrite laser (dual-wavelength). We assessed treatment responses (according to clearance rate), vascular/hyperkeratosis grades, and patient satisfaction and pain ratings. The differences in treatment response (p = .348), patient satisfaction (p = .560), and pain ratings (p = .728) between the groups were not significant. The single- and dual-wavelength treatment options were equally effective in treating recalcitrant palmoplantar warts.


Magnetic stimulation at acupoints relieves mental fatigue: An Event Related Potential (P300) study.
Mental fatigue caused by continuous cognitive tasks represents one of the most worrying modern health problems. Event Related Potential (ERP) P300 is thought to be associated with cognitive function. This study aimed at characterizing the neural activity correlated with the attentional processes and exploring a novelty method which combine the magnetic stimulation and acupoint to relieve mental fatigue caused by continuous cognitive tasks. P300 (P3a and P3b) were extracted at three points: when subjects felt relaxed, at the point of mental fatigue, and after the subjects were stimulated at acupoints. The amplitudes and latencies of P3a and P3b were analyzed statistically. Among the four features (P3a amplitude, P3a latency, P3b amplitude, and P3b latency), only P3b amplitude was found to have a significant difference between the resting state and the mental fatigue state. And P3b amplitude significantly increased after magnetic stimulation at the acupoints. Subjects experiencing mental fatigue demonstrated a significant decrease in P3b amplitude in the parietal region, suggesting attenuation of resource allocation for selective attention. P3b amplitude significantly increased after magnetic stimulation at acupoints indicating that this strategy can be used to improve selective attention and relieve mental fatigue.


Basics of evidence-based practice. Part 1: The nature of the evidence.
Basics of evidence-based practice are presented in 2 parts. Part 1 explores the characteristics of evidence used in evidence-based practice. Part 2 presents basic terms and processes of EBP. The nature of the evidence as the basis for clinical decisions is a major distinction between the new paradigm of evidence-based practice and yesterday's approaches to research utilization. This article discusses why research evidence is the best source of clinical knowledge, and why systematic reviews, in particular, provide the most stable knowledge for clinical practice. Sources of evidence summaries, such as Agency for Healthcare Research and Quality, are also discussed.


Addition of plant-growth-promoting Bacillus subtilis PTS-394 on tomato rhizosphere has no durable impact on composition of root microbiome.
Representatives of the genus Bacillus are increasingly used in agriculture to promote plant growth and to protect against plant pathogens. Unfortunately, hitherto the impact of Bacillus inoculants on the indigenous plant microbiota has been investigated exclusively for the species Bacillus amyloliquefaciens and was limited to prokaryotes, whilst eukaryotic member of this community, e.g. fungi, were not considered. The root-colonizing Bacillus subtilis PTS-394 supported growth of tomato plants and suppressed soil-borne diseases. Roche 454 pyrosequencing revealed that PTS-394 has only a transient impact on the microbiota community of the tomato rhizosphere. The impact on eukaryota could last up to 14 days, while that on bacterial communities lasted for 3 days only. Ecological adaptation and microbial community-preserving capacity are important criteria when assessing suitability of bio-inoculants for commercial development. As shown here, B. subtilis PTS-394 is acting as an environmentally compatible plant protective agent without permanent effects on rhizosphere microbial community.


Investigating the possibility of a monitoring fast ion diagnostic for ITER.
In burning plasma fusion devices, fast ion transport plays a central role in the performances of the machines. Moreover the losses of energetic particles might cause severe damages on plasma facing components. Therefore real time measurements of fast ion transport would provide valuable information for safe and reliable plasma operations. In this paper, we examine the feasibility of a monitoring system based on active charge exchange recombination spectroscopy making use of the 0.5 MeV/amu ITER heating neutral beams for detecting fast (4)He(+2) (alphas) particles in ITER plasmas. There are two time scales relevant to fast ion dynamics: the first is the slowing down time of the distribution function which is of the order of 1 s, and the second is the time scale of burstlike transport events such as collective Alfven mode excitations, which--for typical ITER plasma parameters--can be as low as 0.2-1 ms. To detect such fast events a broadband high-throughput spectrometer is needed, while for the reconstruction of the alpha velocity distribution function a higher resolution spectrometer and longer integration time are necessary. To monitor a spatial redistribution of fast particles due to the propagation of the instability, it is proposed to use a limited number of spatial channels, looking at the charge exchange He II spectra induced by the heating beams, whose energy matches the slowing down energies of fast particles. The proposal is to share the motional stark effect periscope on equatorial port 3 [A. Malaquias et al., Rev. Sci. Instrum. 75, 3393 (2004)] adding additional fibers and suitable instruments. A signal to noise ratio of 5 could be achieved with a spatial resolution of a/15 and a time resolution of 5 ms, in a broad spectral band of 100 A, corresponding to the spectral broadening of the line emitted by alpha particles with energies DeltaE < or = 1.5 MeV. Fast H and D ion populations created by heating neutral beam or ion cyclotron resonance heating are expected to produce significantly lower charge exchange signal levels and can only be monitored on substantially longer time scales as it is expected because of the strong energy difference with respect to the heating neutral beam and the consequently low charge exchange cross sections.


Modulation of actin affinity and actomyosin adenosine triphosphatase by charge changes in the myosin motor domain.
The effects of mutations in an actin-binding surface loop of myosin (loop 2) are described. Part of loop 2, the segment between myosin residues 618 and 622, was replaced with sequences enlarged by the introduction of positively charged GKK or neutral GNN motifs. Constructs with loops carrying up to 20 additional amino acids and charge variations from -1 to +12 were produced. Steady-state and transient kinetics were used to characterize the enzymatic behavior of the mutant motor domains. Binding of nucleotide was not affected by any of the alterations in loop 2. In regard to their interaction with actin, constructs with moderate charge changes (-1 to +2) displayed wild-type-like behavior. Introduction of more than one GKK motif led to stronger coupling between the actin- and nucleotide-binding sites of myosin and an up to 1000-fold increased affinity for actin in the absence of ATP and at zero ionic strength. In comparison to the wild-type construct M765, constructs with 4-12 extra charges displayed an increased dependence on ionic strength in their interaction with actin, a 2-3-fold increase in kcat, a more than 10-fold reduction in Kapp for actin, and a 34-70-fold increase in catalytic efficiency.


Mesonephric-like adenocarcinoma of the female genital tract: possible role of KRAS-targeted treatment-detailed molecular analysis of a case series and review of the literature for targetable somatic KRAS-mutations.
Mesonephric-like adenocarcinomas (MLA) of the female genital tract represent a rare and relatively recently described neoplasm exhibiting characteristic morphologic and immunohistochemical findings commonly associated with a KRAS-mutation. Most cases display an aggressive clinical behavior, but knowledge about treatment approaches is limited, especially for targeting KRAS. We report a series of eight cases with a detailed molecular analysis for KRAS. These cases as well as the data of previously published cases with detailed information regarding KRAS-mutational events were reviewed for a potential targeted approach and its prognostic impact. Both the uterine and ovarian MLA harbor a somatic KRAS-mutation in about 85% of the reported cases, affecting the hotspot codons 12 and 13. 15.7% of the endometrial and 15.6% of ovarian MLA are wild type for KRAS. A p.G12A-alteration was seen in 5.6% (5/89) of the endometrial and in 6.2% (2/32) of the ovarian tumors, for p.G12C in 7.9% and 6.2%, for p.G12D in 32.6% and 34.5% and for p.G12V in 36% and 37.5%, respectively. Very limited data are available regarding the prognostic impact of different mutational sites within the KRAS-gene without significant prognostic impact. Because of a specific p.G12C-KRAS somatic mutation, only the minority of MLA (7.9% with uterine and 6.2% with ovarian primary) are potentially targetable by sotarasib in that rare but aggressive subtype of adenocarcinoma of the female genital tract. Until now, the different location of a somatic KRAS-mutation is of no prognostic impact.


Particle size variations in the glass component of glass-ionomer dental cements.
Glass polyalkenoate cements (glass ionomer cements) are widely used in restorative dentistry and now a day the material of choice for bone cements. The aim of the study is to examine the variations produced by exposure to acid for dental Glass Ionomer Cement (GIC) glass particles of different composition. It also involves the study of the effect of replacing Ca by Sr in glass ionomer glasses on the particle size distribution. This study was carried out in a Malvern Mastersizer/E. This uses LASER-diffraction and was in reverse-Fourier mode (0.1-80 microm). Ultrasound was used to break up any agglomerates. Also, some samples were treated as above but instead of particle size analyser, the slurries were centrifuged and the glass washed and dried to constant weight to determine mass loss. The mass loss for LG26Sr in acid washing was comparatively greater whereas LG26 showed less mass loss. When statistically evaluated LG series and AH2 were found to differ significantly p = 0.008. There was, however, no significant difference between other combinations of glasses in acid was treatment. The pseudo-cement formation in all the glasses suffered significant mass loss p = < 0.008. By changing the different chemical composition of glass ionomer glasses the mass loss was substantially greater during the cement formation process as compare to acid washing.


Colorectal carcinoma and myelopathy.
The incidence and pathological features of colorectal carcinoma in a population of veterans disabled by myelopathy were examined by record review. Thirteen cases of colorectal carcinoma were found among the 1023 such individuals (99 percent male) who were hospitalized and subsequently followed between April 1, 1973 and September 22, 1983. The age adjusted incidence rates ranged from 316 per 100,000 person years in the sixth decade to 1886 per 100,000 person years in the ninth decade of age. These rates were two to six times the highest reported rates for general male populations (P less than 0.05). The location of carcinoma was proximal to the rectosigmoid colon in 62 percent of the 13 paralyzed patients, but in only 12 percent of 31 nonparalyzed male patients with colorectal carcinoma diagnosed at the same hospital in 1977-1979 (P less than 0.001). The stage of the tumor at diagnosis was Dukes Kirklin C in 83 percent of paralyzed patients and 48 percent of the nonparalyzed patients (P less than 0.001). We conclude that colorectal carcinoma is more common, more proximal in location, and more advanced at diagnosis in male subjects with myelopathy than in nonparalyzed male subjects.


The use of a biphasic calcium phosphate in a maxillary sinus floor elevation procedure: a clinical, radiological, histological, and histomorphometric evaluation with 9- and 12-month healing times.
This study evaluates the clinical, radiological, histological, and histomorphometric aspects of a fully synthetic biphasic calcium phosphate (BCP) (60% hydroxyapatite and 40% ß-tricalcium phosphate), used in a human maxillary sinus floor elevation (MSFE) procedure with 9- and 12-month healing time. A unilateral MSFE procedure, using 100% BCP, was performed in two series of five patients with healing times of 9 and 12 months respectively. Clinical and radiological parameters were measured up to 5 years postoperatively. Biopsy retrieval was carried out during dental implants placement. Histology and histomorphometry were performed on 5-μm sections of undecalcified bone biopsies. The MSFE procedure with BCP showed uneventful healing in all cases. All dental implants appeared to be well osseointegrated after 3 months. Radiological evaluation showed less than 1 mm tissue height loss from MSFE to the 5-year follow-up examination. No signs of inflammation were detected on histological examination. Newly formed mineralized tissue was found cranially from the native bone. The BCP particles were surrounded by connective tissue, osteoid islands, and newly formed bone. Mineralized bone tissue was in intimate contact with the BCP particles. After 12 months, remnants of BCP were still present. The newly formed bone had a trabecular structure. Bone maturation was demonstrated by the presence of lamellar bone. Histomorphometric analysis showed at 9 and 12 months respectively an average vital bone volume/total volume of 35.2 and 28.2%, bone surface/total volume of 4.2 mm2/mm3 and 8.3 mm2/mm3, trabecular thickness of 224.7 and 66.7 μm, osteoid volume/bone volume of 8.8 and 3.4%, osteoid surface/bone surface (OS/BS) of 42.4 and 8.2%, and osteoid thickness of 93.9 and 13.6 μm. MFSE with BCP resulted in new bone formation within the augmented sinus floor and allowed the osseointegration of dental implants in both groups. From a histological and histomorphometric perspective, a 9-month healing time for this type of BCP may be the optimal time for placement of dental implants.


Potential role of salivary cortisol levels to reflect stress response in children undergoing congenital heart surgery.
This study aimed to provide baseline information on the potential role of salivary cortisol in reflecting the stress response in children undergoing congenital heart surgery. Children underwent congenital cardiac surgery, aged between one and seventeen years were included. Saliva samples were collected pre- and postoperatively by the health caregiver immediately after the children woke up (07:00-09:00 am) and at 06:00 pm in the evening. Salivary cortisol levels were compared with the reference index values from a large database. Median baseline preoperative morning salivary cortisol levels were significantly lower than the reference values in both < 5-year-old females (p = 0.01) and males (p = 0.04) and in males between 11 and 20 years of age (p = 0.01). Median baseline preoperative evening salivary cortisol levels were significantly higher than the reference value in < 5-year-old females (p = 0.01) and between 5 and 10 years of age (p = 0.04) and in between 11- and20-year-old males (p = 0.01). Median postoperative morning salivary cortisol levels were significantly lower than the reference value in both < 5-year-old females (p = 0.01) and males (p = 0.04) and females between 5 and 10 year of age (p = 0.04). Median postoperative evening salivary cortisol levels were significantly higher than the reference value in < 5-year-old females (p = 0.01) and between 5- and 10-year-old females (p = 0.04). Diurnal variability of salivary cortisol levels in children undergoing congenital heart surgery may be different from normal reference values both in preoperative and postoperative periods that can be a predictive indicator of anxiety on pre- and postoperative period for children that undergoing cardiac surgery.


Chitosan bio-based organic-inorganic hybrid aerogel microspheres.
Recently, organic-inorganic hybrid materials have attracted tremendous attention thanks to their outstanding properties, their efficiency, versatility and their promising applications in a broad range of areas at the interface of chemistry and biology. This article deals with a new family of surface-reactive organic-inorganic hybrid materials built from chitosan microspheres. The gelation of chitosan (a renewable amino carbohydrate obtained by deacetylation of chitin) by pH inversion affords highly dispersed fibrillar networks shaped as self-standing microspheres. Nanocasting of sol-gel processable monomeric alkoxides inside these natural hydrocolloids and their subsequent CO(2) supercritical drying provide high-surface-area organic-inorganic hybrid materials. Examples including chitosan-SiO(2), chitosan-TiO(2), chitosan-redox-clusters and chitosan-clay-aerogel microspheres are described and discussed on the basis of their textural and structural properties, thermal and chemical stability and their performance in catalysis and adsorption.


Considerations in the use of microneedles: pain, convenience, anxiety and safety.
Transdermal delivery using microneedles is gaining increasing attention from pharmaceutical and cosmetic companies as one of the promising drug delivery methods. Microneedle products have recently become available on the market, and some of them are under evaluation for efficacy and safety. To be available in the market for cosmetic and therapeutic use, several factors should be considered, including pain, anxiety, convenience and safety. These factors are summarized and reviewed in this article according to type of microneedle. Various kinds of materials have been used for manufacturing microneedles and developing drug formulations for microneedles. Safety information about materials used for microneedles is summarized in terms of type of microneedles. In addition to their biocompatibility, mechanical safety is also discussed. This review can provide guidelines for designing microneedle products for proper use.


TMED2 binding restricts SMO to the ER and Golgi compartments.
Hedgehog (HH) signaling is important for embryonic pattering and stem cell differentiation. The G protein-coupled receptor (GPCR) Smoothened (SMO) is the key HH signal transducer modulating both transcription-dependent and transcription-independent responses. We show that SMO protects naive mouse embryonic stem cells (ESCs) from dissociation-induced cell death. We exploited this SMO dependency to perform a genetic screen in haploid ESCs where we identify the Golgi proteins TMED2 and TMED10 as factors for SMO regulation. Super-resolution microscopy shows that SMO is normally retained in the endoplasmic reticulum (ER) and Golgi compartments, and we demonstrate that TMED2 binds to SMO, preventing localization to the plasma membrane. Mutation of TMED2 allows SMO accumulation at the plasma membrane, recapitulating early events after HH stimulation. We demonstrate the physiologic relevance of this interaction in neural differentiation, where TMED2 functions to repress HH signal strength. Identification of TMED2 as a binder and upstream regulator of SMO opens the way for unraveling the events in the ER-Golgi leading to HH signaling activation.


Effect of phosphate on the second cleavage division of the rat embryo.
Development of the rat embryo is arrested at the 2-cell stage in vitro in the presence of inorganic phosphate (Pi). Rat embryos were affected by exposure to 1.19 mM KH2PO4 in modified hamster embryo culture medium-1 at the late 2-cell stage only. When exposure durations were 6 h, embryos whose exposure timings were prior to cleavage had a reduced rate of development to the blastocyst stage (2-8%) when compared with embryos with no exposure to Pi (97%, P < 0.05). When exposure durations were 18 h, all embryos were arrested at the 2- to 4-cell stage. These timings would correspond to the G2 to M phase of the second cell cycle. Maturation-promoting factor (MPF), which is regulated by a phosphorylation cascade, controls cell division, and its kinase activity is necessary in order for the cell to enter the M phase. However, the histone H1 kinase activity levels and the patterns of the state of phosphorylation of cdc2 were the same in blocked and non-blocked embryos. Because MPF was active in blocked embryos, the developmental block in rat 2-cell embryos caused by phosphate was not due to MPF activity or its phosphorylation cascade.


New alpha-L-arabinofuranosidase produced by Streptomyces lividans: cloning and DNA sequence of the abfB gene and characterization of the enzyme.
A fully secreted alpha-l-arabinofuranosidase was cloned from the homologous expression system of Streptomyces lividans. The gene, located upstream adjacent to the previously described xylanase A gene, was sequenced. It is divergently transcribed from the xlnA gene and the two genes are separated by an intercistronic region of 391nt which contains a palindromic AT-rich sequence. The deduced amino acid sequence of the protein shows that the enzyme contains a distinct catalytic domain which is linked to a specific xylan-binding domain by a linker region. The purified enzyme has a specific arabinofuranose-debranching activity on xylan from Gramineae, acts synergistically with the S. lividans xylanases and binds specifically to xylan. From small arabinoxylo-oligosides, it liberates arabinose and, after prolonged incubation, the purified enzyme exhibits some xylanolytic activity as well.


Oxytocin and vasopressin: linking pituitary neuropeptides and their receptors to social neurocircuits.
Oxytocin and vasopressin are pituitary neuropeptides that have been shown to affect social processes in mammals. There is growing interest in these molecules and their receptors as potential precipitants of, and/or treatments for, social deficits in neurodevelopmental disorders, including autism spectrum disorder. Numerous behavioral-genetic studies suggest that there is an association between these peptides and individual social abilities; however, an explanatory model that links hormonal activity at the receptor level to complex human behavior remains elusive. The following review summarizes the known associations between the oxytocin and vasopressin neuropeptide systems and social neurocircuits in the brain. Following a micro- to macro- level trajectory, current literature on the synthesis and secretion of these peptides, and the structure, function and distribution of their respective receptors is first surveyed. Next, current models regarding the mechanism of action of these peptides on microcircuitry and other neurotransmitter systems are discussed. Functional neuroimaging evidence on the acute effects of exogenous administration of these peptides on brain activity is then reviewed. Overall, a model in which the local neuromodulatory effects of pituitary neuropeptides on brainstem and basal forebrain regions strengthen signaling within social neurocircuits proves appealing. However, these findings are derived from animal models; more research is needed to clarify the relevance of these mechanisms to human behavior and treatment of social deficits in neuropsychiatric disorders.


Continuous Glucose Monitoring in Transient Neonatal Diabetes Mellitus-2 Case Reports and Literature Review.
Neonatal diabetes mellitus is a rare genetic disease that affects 1 in 90,000 live births. The start of the disease is often before the baby is 6 months old, with rare cases of onset between 6 months and 1 year. It is characterized by low or absent insulin levels in the blood, leading to severe hyperglycemia in the patient, which requires temporary insulin therapy in around 50% of cases or permanent insulin therapy in other cases. Two major processes involved in diabetes mellitus are a deformed pancreas with altered insulin-secreting cell development and/or survival or faulty functioning of the existing pancreatic beta cell. We will discuss the cases of two preterm girls with neonatal diabetes mellitus in this research. In addition to reviewing the literature on the topic, we examined the different mutations, patient care, and clinical outcomes both before and after insulin treatment.


Self-Other Differences in Perceiving Why People Eat What They Eat.
People often view themselves more favorably than others, displaying unrealistic optimism. In the present study, we investigated whether people perceive their reasons for eating as better than those of others. Furthermore, we investigated which mechanisms of inaccuracy might underlie a possible bias when perceiving why people eat what they eat. In Study 1, 117 participants rated the social desirability of eating motives. In Study 2, 772 participants provided information on their own and others' motives for eating behavior. In Study 1, particularly desirable motives were eating because of hunger, health reasons, and liking. Particularly undesirable motives were eating to make a good impression, to comply with social norms, and to regulate negative affect. Study 2 revealed that for socially desirable motives, participants perceived their own motives to be stronger; for undesirable motives, the opposite pattern emerged, with others being attributed stronger motives. Moreover, the perception of others' emotional and social motives varied with participants' own healthy eating behavior. Since the perception of eating motives of others should be independent of one's own behavior, this pattern of results indicates a relative inaccuracy in the perception of others' eating motives. In conclusion, there is evidence for unrealistic optimism in eating motives. For social and emotional motives, this self-favoring view seems to be driven by a relatively inaccurate perception of others.


Low lumbar bone mineral density in patients with major depression.
Major depression is associated with hypercorticoidism, a risk factor for osteoporosis. However, it is unknown whether depressive disorders are associated with alterations in bone mineral density. The authors measured the density of trabecular bone from the first to the third lumbar vertebra by quantitative computerized tomography in 80 depressed inpatients older than 40 years and in 57 healthy comparison subjects. An analysis of covariance model with age as a covariate showed a significant effect of diagnosis on the dependent variable spinal bone mineral density: depressed patients had lower values. Other factors could not explain the finding. The authors conclude that major depression is a significant risk factor for osteoporosis.


Synthesis and evaluation of 1,ω-bis(1,2,3,5-thiatriazol-5-yl)alkanes as in vitro and in vivo α-amylase and lipase inhibitors.
Thionyl chloride reacts with 1,ω-bis-(1-tosylamidrazone)alkanes 1 to give a series of 1,ω-bis-(4-alkyl-2-tosyl-1,2,3,5-thiatriazol-5-yl)alkanes 2. All the newly synthesized compounds were characterized by IR, 1H NMR, 13C NMR, elemental analysis, and ESI-MS spectral data. All the new compounds were screened for their inhibitory effect on key enzymes related to diabetes and obesity, such as α-amylase and lipase. In vitro and in vivo studies revealed that these thiatriazole derivatives exert an inhibitory action against these key enzymes. Moreover the administration of these compounds to surviving diabetic rats induced a significant decrease in plasma glucose level. Additively 2d significantly protected the liver-kidney functions and modulated lipid metabolism, which were evidenced by the decrease in aspartate transaminase (AST), alanine transaminase (ALT), and gamma-glutamyl transpeptidase (GGT) activities and creatinine, urea albumin, LDL-cholesterol and triglycerides levels as well as an increase in the HDL-cholesterol level in surviving diabetic rats. Overall, the findings of the current study indicate that 2d exhibits attractive properties and can, therefore, be considered for future application in the development of anti-diabetic and hypolipidemic drugs.


Theoretical research on reasonable shield support capacity in close-multiple coal seams with the coordinated mining: A case study of Qianjiaying coal mine.
In order to assess the rationality of the rated shield support capacity (RSSC) experienced selection and guide the reasonable RSSC selection for the subsequent working faces of each coal seam, the coupling relationship between shield and roof strata was revealed during each coal seams mining. According to whether the fractured rock blocks generated by the main roof are articulated and whether the upper coal seam has been mined and influenced on the lower coal seam, two roof structure mechanical models of the rock blocks generated by the thick main roof and two calculation methods of a given load on the rock blocks are proposed. In addition, a selection method of roof structure model for maximum shield support capacity (MSSC) of close-multiple coal seams with the coordinated mining is put forward. Three roof structures to calculate the MSSC are established. Based on a case study of close-multiple coal seams with the coordinated mining in the Qianjiaying coal mine, the MSSC is calculated and analyzed in each coal seam combined with roof structure characteristics description, theoretical analysis, and field measurement. No.7, No.12-1, and No.5 coal seams mining are applicable to a voussoir beam balanced structure. No.8 coal seam mining is applicable to a balanced structure with a given load of loose body. No.9 coal seam mining is applicable to a voussoir beam balanced structure with a given load of loose body. Through the calculation, the MSSC of No.7, No.8, No.12-1, No.9, and No.5 coal seam is 3948.55kN, 4018.32kN, 4101.63kN, 3560.03kN, and 4015.30kN, respectively. And the RSSC suggested selection of each coal seam is 4500kN, 4300kN, 4300kN, 4000kN, and 4300kN, respectively. By field measurement, the RSSC experienced selection of each coal seam in the Qianjiaying coal mine is unreasonable with low support load utilization. However, after adopting the RSSC suggested selection in each coal seam, the support load utilization increased by 29.07%, 9.6%, 8.57%, 15.33%, and 11.39%.


Effects of mechanical and chemical surface treatments on the resin-glass ceramic adhesion properties.
Intraoral repair of fractured ceramic restorations using resin composite is practical for dental treatment. In the present study, we investigated whether differences in surface treatments for glass ceramic would affect resin adhesion. Leucite-reinforced glass ceramic plates (IPS Empress Esthetic) were ground with 320-grit silicon carbide paper, cleaned using phosphoric acid, and then etched with hydrofluoric acid (IPS Ceramic Etching Gel) or left unetched, and silanized using silane coupling agent (RelyX Ceramic Primer) or kept unsilanized. Either conventional (Adper Scotchbond Multi-Purpose) or universal (Scotchbond Universal) adhesive was used to bond the resin composite to ceramic surfaces. Specimens were subjected to microshear test after 37°C water storage for 24 h, and fractured surfaces were examined. Ceramic surface hydrophobicity after treatments was verified with contact angle measurements. Data were analyzed using anova and Tukey's tests. Regardless of the adhesive tested, hydrofluoric acid-etched ceramics showed higher bond strengths. Ceramic primer application improved resin bonding, even in non-etched groups, and also influenced fractography (P < 0.001). Contact angles on ceramics treated with ceramic primer were higher than those treated with silane-containing universal adhesive (P < 0.001). Mechanical and chemical retentions contribute to resin adhesion to glass ceramic. Universal adhesive seems to not function in the same manner as a silane coupling agent.


Tracking medical students' clinical experiences with a computerized medical records system.
A fully computerized system for recording and reporting of medical students' patient contacts has been developed and successfully used in a high-volume outpatient practice. In contrast to previously described systems, the need for manual recording and/or entry of patient data has been eliminated by the use of an existing, integrated computerized medical records system. This makes possible the generation of frequent reports and timely review and adjustment of student experiences. The system has broad applicability and may also be useful for research in medical education.


Voltammetric Perspectives on the Acidity Scale and H+/H2 Process in Ionic Liquid Media.
Nonhaloaluminate ionic liquids (ILs) have received considerable attention as alternatives to molecular solvents in diverse applications spanning the fields of physical, chemical, and biological science. One important and often overlooked aspect of the implementation of these designer solvents is how the properties of the IL formulation affect (electro)chemical reactivity. This aspect is emphasized herein, where recent (voltammetric) studies on the energetics of proton (H+) transfer and electrode reaction mechanisms of the H+/H2 process in IL media are highlighted and discussed. The energetics of proton transfer, quantified using the p Ka (minus logarithm of acidity equilibrium constant, Ka) formalism, is strongly governed by the constituent IL anion, and to a lesser extent, the IL cation. The H+/H2 process, a model inner-sphere reaction, also displays electrochemical characteristics that are strongly IL-dependent. Overall, these studies highlight the need to carry out systematic investigations to resolve IL structure and function relationships in order to realize the potential of these diverse and versatile solvents.


Proteomics and redox-proteomics of the effects of herbicides on a wild-type wine Saccharomyces cerevisiae strain.
Several toxicological and environmental problems are associated with the extensive use of agricultural pesticides, such as herbicides. Nevertheless, little is known about the toxic effects of formulated herbicides, since many studies have been carried out using pure active molecules alone. In this work, we used as an eukaryotic model system an autochthonous wine yeast strain to investigate the effects of three commercial herbicides, currently used in the same geographical area from where this strain had been isolated. We carried out a comparative proteomic analysis to study the effects at the protein level of the herbicide-related stress, and found that the herbicides tested can alter the yeast proteome producing responses that share homologies with those observed treating yeast cells with the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) or with well-known oxidizing agents. We evaluated, through redox-proteomic techniques, protein carbonylation as a biomarker of oxidative stress. This analysis showed that herbicide-induced carbonylation is a dynamic phenomenon with degrees of selectivity.


Modulation of steroidogenic gene expression and hormone production of H295R cells by pharmaceuticals and other environmentally active compounds.
The H295R cell bioassay was used to evaluate the potential endocrine disrupting effects of 18 of the most commonly used pharmaceuticals in the United States. Exposures for 48 h with single pharmaceuticals and binary mixtures were conducted; the expression of five steroidogenic genes, 3betaHSD2, CYP11beta1, CYP11beta2, CYP17 and CYP19, was quantified by Q-RT-PCR. Production of the steroid hormones estradiol (E2), testosterone (T) and progesterone (P) was also evaluated. Antibiotics were shown to modulate gene expression and hormone production. Amoxicillin up-regulated the expression of CYP11beta2 and CYP19 by more than 2-fold and induced estradiol production up to almost 3-fold. Erythromycin significantly increased CYP11beta2 expression and the production of P and E2 by 3.5- and 2.4-fold, respectively, while production of T was significantly decreased. The beta-blocker salbutamol caused the greatest induction of CYP17, more than 13-fold, and significantly decreased E2 production. The binary mixture of cyproterone and salbutamol significantly down-regulated expression of CYP19, while a mixture of ethynylestradiol and trenbolone, increased E2 production 3.7-fold. Estradiol production was significantly affected by changes in concentrations of trenbolone, cyproterone, and ethynylestradiol. Exposures with individual pharmaceuticals showed the possible secondary effects that drugs may exert on steroid production. Results from binary mixture exposures suggested the possible type of interactions that may occur between drugs and the joint effects product of such interactions. Dose-response results indicated that although two chemicals may share a common mechanism of action the concentration effects observed may be significantly different.


Group-Based Trajectory Modelling of Changes in Mobility over Six Years in Type 2 Diabetes: The Fremantle Diabetes Study Phase II.
To investigate temporal changes in mobility in community-based people with type 2 diabetes, Fremantle Diabetes Study Phase II (FDS2) data were analysed. The baseline assessment included the Timed Up and Go (TUG) test, which was repeated biennially for up to six years. Group-based trajectory modelling (GBTM) identified TUG trajectory groups in participants with ≥2 tests. Independent associates of group membership were assessed using multinomial regression. Of 1551 potential FDS2 participants, 1116 (72.0%; age 64.9 ± 11.0 years, 45.6% female) were included in the modelling. The best-fitting GBTM model identified two groups with linear, minimally changing trajectories (76.2% and 19.4% of participants; baseline TUG times 8 ± 2 and 12 ± 3 s, respectively), and a third (4.5%; baseline TUG 17 ± 5 s) with a TUG that increased over time then fell at Year 6, reflecting participant attrition. Both slower groups were older, more likely to be female, obese, and had greater diabetes-associated complications and comorbidities. Almost one-quarter of the FDS2 cohort had clinically relevant mobility impairment that persisted or worsened over six years, was multifactorial in origin, and was associated with excess late withdrawals and deaths. The TUG may have important clinical utility in assessing mobility and its consequences in adults with type 2 diabetes.


Self-harm and suicidal behavior in borderline personality disorder with and without bulimia nervosa.
Few studies have investigated whether a diagnosis of Bulimia nervosa (BN) confers additional risk of life-threatening behaviors such as self-harm and suicidal behavior in borderline personality disorder (BPD). Participants were 483 treatment-seeking women diagnosed with BPD according to the Structured Clinical Interview for DSM-IV Axis II Personality Disorders (SCID-II; First, Gibbon, Spitzer, Williams, & Benjamin, 1997; Diagnostic and Statistical Manual of Mental Disorders, 4th ed.; APA, 1994) and admitted to the Norwegian Network of Psychotherapeutic Day Hospitals between 1996 and 2009. Of these, 57 (11.8%) women met DSM-IV diagnostic criteria for BN according to the Mini-International Neuropsychiatric Interview (M.I.N.I.; Sheehan et al., 1998) and they were compared with women with BPD and other Axis I disorders. We found that comorbid BN is uniquely and significantly associated with increased risk of suicidal behavior among women being treated for BPD. Findings underscore the importance of routinely screening for BN among women seeking treatment for BPD, as co-occurring bulimia appears to be a significant marker for immediate life-threatening behaviors in this already high-risk population, which is a significant public health issue. A significantly greater proportion of women with BPD-BN reported suicidal ideation at intake (past 7 days), engaged in self-harm behavior during treatment, and attempted suicide during treatment. All bivariate associations remained significant in the logistic regression models after controlling for mood, anxiety, and substance-related disorders. The presence of a concurrent diagnosis of BN among women with BPD is significantly and uniquely associated with recent suicidal ideation, and self-harm behavior and suicide attempts during treatment after controlling for major classes of mental disorders. Co-occurring BN appears to represent a significant marker for immediate life-threatening behaviors in women seeking treatment for BPD. Extra vigilance and careful monitoring of suicidal behavior during treatment is important for these individuals, and routine screening for BN is warranted.


Evaluation of China-ASEAN trade status and trade potential: An empirical study based on a gravity model.
The objective of this study was to identify factors influencing the development of China-ASEAN trade- from the total economic volume of both sides, distance, the population size of ASEAN countries, the construction of a free trade area, and the signing of the Belt and Road initiative, resource endowment per capita, the exchange rate between RMB and ASEAN countries, and the land area of ASEAN countries-to develop a conceptual framework for China-ASEAN trade potential. This study uses panel data from 2001 to 2021 that is evenly distributed among 10 ASEAN countries to serve as the dataset. Firstly, the unit roots are checked and the cointegration relationships are examined, focusing on the heterogeneity test. Based on the classical trade gravity model, the innovative trade gravity model with key influencing factors is constructed. On the basis of the classical trade gravity model, an innovative trade gravity model of key influencing factors is constructed. The trade potential model is used to calculate the direct trade potential coefficient between China and ASEAN countries, which points out the direction for the sustainability of bilateral trade. This study finds that among the factors affecting China-ASEAN bilateral trade, the total economic output of both sides, distance, population size of ASEAN countries, the construction of the FTA, and the signing of the Belt and Road Initiative all have a positive impact on bilateral trade. Three influencing factors, namely per capita resource endowment, exchange rate between RMB and ASEAN countries, and the size of ASEAN countries, have a negative impact on bilateral trade, but to a lesser extent. The trade potential between China and Vietnam falls into the category of potential re-modelling, indicating that both sides are currently utilizing their trade potential to the greatest extent possible, that trade growth space is limited, and that new trade opportunities must be discovered. The trade potential index between China and nine ASEAN countries, excluding Vietnam, is in the potential-exploiting category, indicating that the potential has not been fully utilized by both sides and that there is still room for growth in the scale of trade between the two countries. With the shift of the world's economic center of gravity in the direction of Asia following COVID-19, China and ASEAN countries should seize the opportunity to strengthen their comprehensive strength and economic aggregates and further develop China's constructive role in the regional organization. The signing of the Belt and Road Initiative and the construction of a free trade zone has had a positive effect on the development of bilateral trade. Propose that: positive trade factors should continue to be strengthened, trade barriers should be removed, and new dynamics of bilateral trade growth should be enhanced.


Bevacizumab Versus Anti-preeclamptic Drugs: Evaluation With Three-dimensionally Co-cultured Human Mini Tumors.
Both bevacizumab (BEV) and soluble fms-like tyrosine kinase-1 (sFlt-1) have demonstrated anti-angiogenic effects, thereby causing hypertension and proteinuria. We hypothesized that anti-preeclamptic drugs that combat the action of sFlt-1 may reduce BEV's anti-tumor efficacy. 3D co-cultured human mini-tumors consisting of endothelial cells, fibroblasts, and cancer cells were developed. The influence of anti-preeclamptic drugs and BEV on the invasion of mini-tumors embedded in collagen gel was evaluated. Mini-tumor spheroids that contained MDA-MB-231 cells showed higher invasion ability than spheroids with A549. Among the six anti-preeclamptic drugs investigated, only nicorandil enhanced the invasion of mini-tumors and inhibited the action of BEV. Glibenclamide, an ATP-sensitive potassium channel inhibitor, completely quenched the action of nicorandil on mini-tumors. In the human mini-tumor model, nicorandil aggravated the invasion of mini-tumors. These data raise the possibility that concomitant use of nicorandil counteracts the efficacy of BEV therapy.


Rhodium(III)-Catalyzed Oxidative Cyclization of Oxazolines with Cyclopropanols: Synthesis of Isoindolinones.
The synthesis of C3-substituted isoindolin-1-ones from oxazolines and cyclopropanols has been achieved with oxazoline as a bifunctional nucleophilic directing group. The reaction proceeds by the cleavage of three chemical bonds and allows the formation of three new chemical bonds, a C-N bond, a C-C bond, and a C-O bond, in a single step.


[Necrotizing fasciitis caused by pseudomonas aeruginosa (an obervation)].
Necrotizing fasciitis is an exceptional and severe form of subcutaneous gangrene which requires early diagnosis and emergency treatment. We report the case of a 24 year old woman presenting with necrotizing fasciitis after pansinusitis resistant to treatment. The germ detected was pseudomonas aeruginosa. The infection was controled with intensive care, antibiotics and surgical resection of necrotic tissues. The aim of this observation is to highlight the clinical characteristics of this disease, and to insist on the necessity to recognize the early symptoms and to start treatment as soon as possible.


Expression of matrix metalloproteinase 9 in patients with oral lichen planus.
Oral Lichen planus (OLP) is chronic inflammatory oral mucosal disease of unknown etiology. Basement membrane damage and T-cell migration in OLP may be mediated by matrix metalloproteinases (MMPs). We examined the expression of matrix metalloproteinase 9 to support this hypothesis. The study population consisted of 71 patients with OLP and 10 control patients with oral fibromas. Indirect immunohistochemistry was used for detection of MMP 9 expression (polyclonal rabbit anti-human MMP antibody). In all cases of OLP, the MMP-9 expression was seen mainly in the area oflymphocytic inflammatory infiltrate in the lamina propria including lymphocytes within the overlying epithelium. In addition, it was observed in the epithelial keratinocytes, particularly in the stratum basale and stratum spinosum with occasional positivity in the superficial layer. Fibroblasts and endothelium of small vessels in the lamina propria showed MMP9 expression as well. In all cases of oral mucosal fibromas, the MMP-9 expression was seen only in fibroblasts and in endothelium of small vessels with occasional positivity within the overlying epithelium. It remains unclear, whether MMP-9 is directly connected to OLP pathogenesis.


Comparative toxicology of monensin sodium in laboratory animals.
The toxicology of monensin has been studied in several laboratory animal species. There was considerable species variation in acute oral LD50 values. The consistent signs of acute toxicity were: anorexia, hypoactivity, skeletal muscle weakness, ataxia, diarrhea, decreased weight gain and delayed deaths. The 3-mo study in rats fed diets containing 0, 50, 150 or 500 ppm monensin resulted in no effects at the lowest dose level, slight reduction of body weight gain in the middle-dose group and severe depression in body weight gain, skeletal and cardiac lesions, and deaths in the highest dose group. The 3-mo study in dogs given daily oral doses of 0, 5, 15 or 50 mg/kg monensin resulted in no effects at the lowest dose level. Dogs in the 15 and 50 mg/kg groups developed, during test wk 1 to 4, anorexia, weakness, ataxia, labored respiration, body weight loss, increased serum muscle enzyme values, severe skeletal muscle degeneration and necrosis with less severe heart lesions and deaths. Mice fed diets containing 0, 37.5, 75, 150 or 300 ppm monensin for 3 mo had reduced body weight gain in all test groups but no other physical signs. Serum creatine phosphokinase (CPK) values were increased in mice in the two highest dose groups and minimal heart lesions were found in the highest dose group. Dogs given daily oral doses of 0, 1.25, 2.5, 5 or 7.5 mg/kg monensin for 1 yr survived with no evidence of toxicity in the two lowest dose groups.(ABSTRACT TRUNCATED AT 250 WORDS)


The effects of Entamoeba histolytica lysates on human colonic mucins.
Detergent lysates of Entamoeba histolytica trophozoites contained high levels of beta-N acetyl-D-glucosaminidase, beta-N acetyl-D-galactosaminidase and alpha-D-galactosidase activity, and lower but significant levels of five other glycosidases. Although these activities should have been capable of largely degrading the oligosaccharide side-chains of human colonic mucin, in fact only about one third of high MW mucin was degraded in 72 h and trypsin alone produced a similar effect. There was no evidence that these glycosidases were excreted and we conclude that they are unlikely to represent significant virulence factors for E. histolytica.


Nematic colloids, topology and photonics.
We review and discuss recent progress in the field of nematic colloids, with an emphasis on possible future applications in photonics. The role of the topology is described, based on experimental manipulations of the topological defects in nematic colloids. The topology of the ordering field in nematics provides the forces between colloidal particles that are unique to these materials. We also discuss recent progress in the new field of active microphotonic devices based on liquid crystals (LCs), where chiral nematic microlasers and tuneable nematic microresonators are just two of the recently discovered examples. We conclude that the combination of topology and microphotonic devices based on LCs provides an interesting platform for future progress in the field of LCs.


Shifting Treatment Paradigms for Ruptured Aneurysms from Open Surgery to Endovascular Therapy Over 25 Years.
Since the introduction of Gugliemi detachable coils in the early 1990s, major clinical studies have supported an increasing role for coil embolization of ruptured aneurysms. We assessed aneurysm location and treatment modality in aneurysmal subarachnoid hemorrhage (aSAH) over the past 25 years. A prospective, institutional review board-approved aneurysm database was screened for patients presenting with aSAH from 1991 to 2016. Microsurgical and endovascular capabilities were present throughout. All patients underwent cerebral angiography prior to treatment. Data were available for 1306/1562 patients (83.6%) presenting with aSAH from 1991-2016. 72% were female, with average age 52.8 years, and average aneurysm size 8.0 mm. The most common vessel of origin was the anterior cerebral artery (37.3%), internal carotid artery (33.3%), and middle cerebral artery (14.6%). Posterior circulation accounted for 14.8% of the aneurysms. Open surgery was performed for 72.4% of aneurysms, endovascular treatment for 22.0%, and 5.7% were not treated. There was an increase in aneurysms treated by endovascular methods over 5-year intervals: 3.0% (1991-1996), 13.4% (1997-2001), 17.2% (2002-2006), 24.3% (2007-2011), and 41.9% (2012-2016). Posterior circulation aneurysms led this trend, increasing from 9.1% endovascular to 71.4%. Endovascular treatment increased from 2.9% and 1.4% of anterior cerebral artery and internal carotid artery aneurysms to 39.6% and 40.7%, respectively, in the most recent 5-year interval. By comparison, endovascular methods remained less commonly used for middle cerebral artery aneurysms (0% initially, now 22.0%). Endovascular treatment of ruptured intracranial aneurysms has steadily increased over the past 25 years at our major academic institution. This is consistent with positive data from clinical trials, advances in endovascular technology, and increasing experience of endovascular specialists.


The antifeedant and antifungal cryptic metabolites isolated from tobacco endophytes induced by host medium and coculture.
Four new cryptic metabolites including one fumagillol derivative (2), one cyclohexenone derivative (4), one 10-membered lactone (5), and one natural 4-epi-brefeldin C (8), along with seven known compounds were found from isogenesis endophytes Aspergillus fumigatus, Penicillium janthinellum, Nigrospora sp., and Stagonosporopsis sp. induced by host Nicotiana tabacum medium and co-culture. The structures were determined mainly by spectroscopic methods, including extensive 1D, 2D NMR, MS techniques, ECD calculation, and Mosher's method. Compound 2 possessed a novel 1, 3-dioxetane residue and cyclohexane-containing terpenoid skeleton. Compounds 2, 4-7 and 10 showed significant antifungal activities against the plant pathogen Nigrospora sp. with MICs of 1 μg/mL. 2, 4, 5-7, and 10 indicated antifungal activities against Penicillium janthinellum, Aspergillus fumigatus, Phomopsis sp., and Alternaria sp. with MICs ≤8 μg/mL. Compounds 2, 6-8, and 10 (50 μg/cm2) and microbial fermentation extracts (100 μg/cm2) showed antifeedant activities against silkworms with feeding deterrence indices of 21-100%.


Enteric Helminths Promote Salmonella Coinfection by Altering the Intestinal Metabolome.
Intestinal helminth infections occur predominantly in regions where exposure to enteric bacterial pathogens is also common. Helminth infections inhibit host immunity against microbial pathogens, which has largely been attributed to the induction of regulatory or type 2 (Th2) immune responses. Here we demonstrate an additional 3-way interaction in which helminth infection alters the metabolic environment of the host intestine to enhance bacterial pathogenicity. We show that an ongoing helminth infection increased colonization by Salmonella independently of T regulatory or Th2 cells. Instead, helminth infection altered the metabolic profile of the intestine, which directly enhanced bacterial expression of Salmonella pathogenicity island 1 (SPI-1) genes and increased intracellular invasion. These data reveal a novel mechanism by which a helminth-modified metabolome promotes susceptibility to bacterial coinfection.


Implementing a clinical decision-support system in practice: a qualitative analysis of influencing attitudes and characteristics among general practitioners.
In order to obtain a better understanding of barriers to the implementation of clinical decision-support systems (CDSSs) in primary health care, we explored general practitioners' (GPs) handling of a CDSS during the implementation process. An Internet-based application for the management of chronic heart failure was used that was an adaptation of established clinical guidelines for computer use. The whole implementation process was followed closely, using a combination of different methods for data collection: repeated interviews with the five participating GPs, observations of patient visits, patient interviews, and detection of usage. We analysed the data using qualitative content analysis. The results showed that GPs' attitudes and characteristics constituted different profiles that seemed to be associated with the degree of acceptance of the CDSS. Those profiles were related to conceptions about the GPs' professional role and their attitudes towards the computer's function in disease management and in decision-making. Some additional barriers were insufficient level of computer skills and time constraints in everyday work. These findings can help us identify groups of GPs with definable needs during the implementation of a CDSS and make it easier to meet those needs with individually tailored interventions.


Effect of JYTK on Antioxidant Status and Inflammation in Patients With Type 2 Diabetes: A Randomized Double-Blind Clinical Trial.
Diabetes is a metabolic disorder caused by oxidative stress and inflammation. JianYuTangKang (JYTK), as a potential Chinese integrative medicine, is an antioxidant used in Chinese medicine with potential anti-inflammatory properties. The present randomized clinical trial was carried out to evaluate the effects of JYTK on oxidative stress and inflammation in patients with type 2 diabetes mellitus (T2DM). The parallel, randomized, double-blinded, placebo-controlled clinical trial included 150 newly diagnosed T2DM patients receiving metformin treatment (1.5 g/day), some of whom also received JYTK (4.5 g/day) in tablet form. The control group received 4.5 g/day placebo plus 1.5 g/day metformin. Body mass index (BMI), fasting plasma glucose, urinary albumin-to-creatinine ratio, and complete blood count as well as antioxidant and inflammation indices such as tumor necrosis factor (TNF)-α, interleukin (IL)-6, superoxide dismutase (SOD), malonaldehyde (MDA), glutathione peroxidase (GPX), and high sensitivity C-reactive protein (hs-CRP) levels were assessed at baseline and at different time points during the treatment. All 112 patients, including 59 in the treatment group (JYTK + metformin) and 52 controls (metformin only) completed the 26-week clinical trial. JYKT plus metformin treatment increased IL-6 (36.4 ± 11.5 ng/L; P < 0.05), TNF-α (17.5 ± 11.3 vs. 22.5 ± 12.9 ng/L; P < 0.05), and MDA (1.9 ± 0.9; P < 0.05) levels compared to the control (2.2 ± 0.6 mM/mL), whereas total SOD level decreased (98.1 ± 30.4 vs. 78.5 ± 29.3 U/mL; P < 0.05). There were no changes in GPX and hs-CRP levels. There were no adverse effects associated with JYTK treatment. JYTK combined with metformin improves some antioxidant indices (SOD and MDA), and decreases inflammation in patients with T2DM, suggesting that it can reduce the risk of diabetic complications.


Acoustic emission during the deformation of alpha-lactose monohydrate and anhydrous alpha-lactose monocrystals.
During the deformation of single crystals of alpha-lactose monohydrate and anhydrous alpha-lactose in a crushing strength rig, their acoustic activity was monitored using a portable activity meter. The acoustic parameters measured were the average signal level (ASL), count rates and total acoustic counts. Both types of lactose, even though deformed by fragmentation, differed fundamentally in the degree and nature of this fragmentation. Close correlation was observed between the ASL, count rate profiles and the force-displacement profiles. The monohydrate form is acoustically more active than the anhydrous form during deformation. Small internal fractures which were neither visually observed nor detected in the force-displacement profiles (in particular the anhydrous alpha-lactose) were detected by monitoring the acoustic signals during the deformation of these crystals. This work illustrates the potential of using the acoustic emission technique as an aid in the assessment of the deformation characteristics of pharmaceutical materials during single crystal compression studies.


Regularized regression analysis of digitized molecular structures in organic reactions for quantification of steric effects.
In organic chemistry, Comparative Molecular Field Analysis (CoMFA) can be defined as a regression analysis between reaction outcomes and molecular fields, wherein we can extract and visualize important structural information from the coefficients of the constructed regression models. In CoMFA, partial least-squares (PLS) regression, which determines all coefficients in the model, is used for fitting the regression models. However, in organic reactions, steric effects are observed only near the reactive site, indicating that a large number of regression coefficients in the CoMFA of organic reactions should be assigned as 0. The regularized regression method, LASSO/Elastic Net, allows us to fit the regression model while assigning 0 values to unimportant coefficients. Although LASSO/Elastic Net should be suitable for CoMFA, there is no example of its use for organic reaction analysis. Herein, we examine the performance of LASSO/Elastic Net for the quantification of steric effects in CoMFA. We employ digitized molecular structures (the indicator field) as molecular fields that represent steric effects. LASSO/Elastic Net regressions provide highly interpretable models that include less noise than those from PLS regression. © 2017 Wiley Periodicals, Inc.