An Enzymatic Route to α-Tocopherol Synthons: Aromatic Hydroxylation of Pseudocumene and Mesitylene with P450 BM3.
Aromatic hydroxylation of pseudocumene (1 a) and mesitylene (1 b) with P450 BM3 yields key phenolic building blocks for α-tocopherol synthesis. The P450 BM3 wild-type (WT) catalyzed selective aromatic hydroxylation of 1 b (94 %), whereas 1 a was hydroxylated to a large extent on benzylic positions (46-64 %). Site-saturation mutagenesis generated a new P450 BM3 mutant, herein named "variant M3" (R47S, Y51W, A330F, I401M), with significantly increased coupling efficiency (3- to 8-fold) and activity (75- to 230-fold) for the conversion of 1 a and 1 b. Additional π-π interactions introduced by mutation A330F improved not only productivity and coupling efficiency, but also selectivity toward aromatic hydroxylation of 1 a (61 to 75 %). Under continuous nicotinamide adenine dinucleotide phosphate recycling, the novel P450 BM3 variant M3 was able to produce the key tocopherol precursor trimethylhydroquinone (3 a; 35 % selectivity; 0.18 mg mL-1 ) directly from 1 a. In the case of 1 b, overoxidation leads to dearomatization and the formation of a valuable p-quinol synthon that can directly serve as an educt for the synthesis of 3 a. Detailed product pattern analysis, substrate docking, and mechanistic considerations support the hypothesis that 1 a binds in an inverted orientation in the active site of P450 BM3 WT, relative to P450 BM3 variant M3, to allow this change in chemoselectivity. This study provides an enzymatic route to key phenolic synthons for α-tocopherols and the first catalytic and mechanistic insights into direct aromatic hydroxylation and dearomatization of trimethylbenzenes with O2 .


Bleeding and liver transplantation outcomes in haemophilia.
Hepatitis C is the major cause of end-stage liver disease and the major indication for orthotopic liver transplantation (OLTx) in individuals with haemophilia. To assess the epidemiology and outcomes of OLTx in U.S. haemophilia patients. We investigated haemophilia liver transplant recipients between 1993 and 2012, using the Nationwide Inpatient Sample, identified by ICD9 code 50.59. Of the 11 267 (weighted n = 54 691) patients undergoing OLTx, 44 (0.4%; weighted n = 213) had haemophilia. Those with haemophilia were more likely than non-haemophilic OLTx recipients to have bleeding complications (45.3% vs. 31.5%, P = 0.009) and hypovolemic shock (7.0% vs. 1.1%, P < 0.0001). They also had a significantly higher incidence of HIV (24.8% vs. 0.5%, P < 0.005), hepatitis B (16.2% vs. 7.9%, P = 0.04) and vitamin K deficiency (2.1% vs. 0.02%, P < 0.001). In spite of these differences, there was no difference in in-hospital mortality between haemophilic and non-haemophilic recipients (6.8% vs. 6.2%, P = 0.9). In multivariate logistic regression, bleeding complications in haemophilia increased the risk of in-hospital mortality by more than 3-fold (P < 0.0001), and disseminated intravascular coagulation increased the risk of bleeding complications in haemophilic recipients by over 10-fold (P < 0.0001). Bleeding complications are common in haemophilia OLTx recipients. Thus, aggressive correction of coagulation defects in this group may be a medically sound approach to reduce complications and mortality associated with OLTx.


Interactions of the female hormonal environment, susceptibility to viral infections, and disease progression.
Sex hormones influence susceptibility and disease predisposition for many genital tract infections. This review describes the mechanisms by which sex steroids affect mucosal immunity, with particular reference to human immunodeficiency virus (HIV) and genital herpes, and the stage-specific effects of hormonal contraception on human papillomavirus (HPV) infection. Estrogen's role is important in the early stages of several infections as it stimulates antibody- and cell-mediated immune responses. There is increased expression of some cytokines in peripheral blood and vaginal fluids during the follicular phase of the menstrual cycle and with use of hormonal contraception. Whether estrogen exerts a protective or deleterious influence depends on the infecting organism and stage of infection or disease. Estrogen apparently reduces susceptibility to primary HPV infection but in the event of persistent HPV infection, sex steroid hormones (estrogen and/or progesterone) are associated with progression to cervical cancer. It is important that these stage-specific effects are better described because most vaccines will try to prevent either infection or disease. Clinicians with patients at high risk of sexually transmitted infections, especially HIV, require better information on the risks associated with different hormonal contraceptive regimes.


[Non typhoidic salmonellosis in the African pediatric population].
The study of non-typhoidic salmonellosis in A. royer pediatric Hospital (Dakar) during a five year term (1985-1989) was realised on thirty five medical records. This pathology accounts for 0.4% of admissions and occurs mainly on children under 3 years old (83%) essentially with a pathologic background. The main clinical forms were septicemia (46%) and gastro-enteritis (31%). Purulent meningitidis represented 45% of all the localized forms. Only one case of asymptomatic carriage has been identified. The seventeen serotypes of Salmonella identified belong to eight serogroups. S. enteritidis and S. typhimurium represented 51% of the isolates. Susceptibility to antibiotics of these different serotypes were variable, the third generation cephalosporins and gentamycin having inhibited more than 80% of the strains. The mean duration of antibiotherapy was 21 days with a mortality rising to 17%. The association ampicilline-gentamycin although criticable, remains indication as first treatment because of the availability of these drugs.


Macrophage-induced muscle pathology results in morbidity and mortality for Ross River virus-infected mice.
Ross River virus (RRV) is an Australian alphavirus that is often responsible for chronic epidemic polyarthritis and myalgia in humans. Past studies have shown severe disruption of striated muscle fibers to be prominent in RRV pathology in mice; in the present study, macrophages were directly implicated as the primary mediators of muscle damage. General immunosuppressive therapies had only minor effects on mortality and morbidity in RRV-infected mice, with no inhibition of muscle damage. Treatment of mice with macrophage-toxic agents (e.g., silica) prior to RRV infection completely abrogated disease symptoms without significantly affecting titers of virus in organs. Further studies found that clinical signs of infection and muscle damage correlated with a massive influx of macrophages into hind leg muscle, whereas no such infiltrate or damage was observed for silica-treated mice. These observations are significant for the human disease context, as monocytic cells have been detected in the synovial effusions of persons with epidemic polyarthritis.


Impressions from a public health group visit to China.
During my trip to China, I saw how many factors interact to influence maternal and child health. These factors cover a broad scope of biologic, behavioral, environmental, and socioeconomic issues. The experience proved to be invaluable. It has helped me to understand how these factors differ--and how they are alike--in China, Canada, and other cultures.


Clinical features and outcomes of microscopic polyangiitis in Korea.
Microscopic polyangiitis (MPA) is a systemic vasculitis affecting small vessels. To determine the clinical features and outcomes of MPA in Korean patients, we retrospectively reviewed the medical records of patients diagnosed with MPA at a single medical center in Korea between 1989 and 2006. The 18 patients who met the Chapel Hill criteria for MPA had a mean (+/-SD) age at the time of diagnosis of 62.4+/-12.7 yr. Renal manifestations and general symptoms were the most common features of MPA, with lung involvement also very common. Antineutrophil cytoplasmic antibodies (ANCA) were present in 17 of the 18 patients (94%). Of 17 patients treated with steroids and cyclophosphamide, 11 (65%) had stable or improved course. One patient treated with steroids without cyclophosphamide showed disease progression. Ten of the 18 patients (56%) died at a median follow-up of 8 months. MPA in Korean patients was distinguished by a higher rate of lung involvement, especially alveolar hemorrhage, which was the leading cause of death in our patients. Korean patients were also older at MPA onset and were more likely positive for ANCA. Other overall clinical manifestations did not differ significantly.


Selectivity and stoichiometry boosting of beta-cyclodextrin in cationic/anionic surfactant systems: when host-guest equilibrium meets biased aggregation equilibrium.
Cationic surfactant/anionic surfactant/beta-CD ternary aqueous systems provide a platform for the coexistence of the host-guest (beta-CD/surfactant) equilibrium and the biased aggregation (monomeric/aggregated surfactants) equilibrium. We report here that the interplay between the two equilibria dominates the systems as follows. (1) The biased aggregation equilibrium imposes an apparent selectivity on the host-guest equilibrium, namely, beta-CD has to always selectively bind the major surfactant (molar fraction > 0.5) even if binding constants of beta-CD to the pair of surfactants are quite similar. (2) In return, the host-guest equilibrium amplifies the bias of the aggregation equilibrium, that is, the selective binding partly removes the major surfactant from the aggregates and leaves the aggregate composition approaching the electroneutral mixing stoichiometry. (3) This composition variation enhances electrostatic attractions between oppositely charged surfactant head groups, thus resulting in less-curved aggregates. In particular, the present apparent host-guest selectivity is of remarkably high values, and the selectivity stems from the bias of the aggregation equilibrium rather than the difference in binding constants. Moreover, beta-CD is defined as a "stoichiometry booster" for the whole class of cationic/anionic surfactant systems, which provides an additional degree of freedom to directly adjust aggregate compositions of the systems. The stoichiometry boosting of the compositions can in turn affect or even determine microstructures and macroproperties of the systems.


Amplification and rearrangement of the Kirsten ras oncogene in virus-transformed BALB/c 3T3 cells during malignant tumor progression.
Analyses of the cellular and viral Kirsten ras genes (c-Ki-ras and v-Ki-ras, respectively) during malignant tumor progression were performed by using Kirsten murine sarcoma virus-transformed BALB/c 3T3 cells that harbor a replication-defective provirus. After injection into athymic nude mice by four different routes, primary tumors and secondary lung metastases were isolated, adapted to in vitro growth, and analyzed for DNA levels and mRNA expression of both genes for comparison with the originally injected transformed cells and untransformed 3T3 cells. For all tumors (primary or secondary), the v-Ki-ras gene was amplified and v-Ki-ras mRNA expression was highly elevated above that observed in the original transformed cell population. In two of five lung metastases from the i.v. and footpad injection routes, rearranged Ki-ras DNA sequences were observed. Micrometastases from the s.c. route of injection did not display these alterations. Injection of footpad lung tumor cells with rearrangements into a second group of animals led to multiple lung metastases with even further rearrangements correlating with more effective lung colonization/growth ability (overt lung tumors in five of eight animals less than 20 days after injection). However, reinjection of an i.v. lung tumor with rearranged Ki-ras led to no further rearrangements in the lung microfoci tumors isolated greater than 40 days after injection. These data suggest (i) the significance of amplification and elevated expression of v-Ki-ras in tumor formation, (ii) correlation of this amplification with more effective tumor progression, and (iii) the selective advantage that cells with Ki-ras DNA sequence additions have in the formation of overt lung tumors.


Impact of the awareness and fear of COVID-19 on menstrual symptoms in women: a cross-sectional study.
The researchers' aim was to determine the impact of the awareness and fear of COVID-19 on menstrual symptoms. We conducted the cross-sectional study with 125 women and collected using the Visual Analog Scale, the Menstruation Symptom Scale, the Awareness of COVID-19 Scale and the Fear of COVID-19 Scale. While 39% of the women reported that there was no change in the menstrual pattern during the pandemic process, 22.4% reported an increase in menstrual pain and 25.6% reported deterioration in the menstrual pattern. A one-unit increase in the women's fear of COVID-19 scale score increases the Menstrual Symptom Scale total score by 1016 points (p < .001). However, the awareness of COVID-19 had no impact on menstrual symptoms. As fear of COVID-19 increases menstrual symptoms, when providing nursing care, nurses should be aware that women need more support to cope with this condition.


Role of the Pubic Symphysis in Osseous Pelvic Development: A Novel Model of Bladder Exstrophy in Rabbits.
It has been posited that the osseous pelvic anomalies seen in patients with classic bladder exstrophy (CBE) result from disruption of the pubic symphysis. This hypothesis, however, has not been tested. In the present animal study, our objective was to determine whether the tension of the pubic symphysis helps maintain the shape of the pelvic ring, or whether the growing bones maintain a ring shape even without the tension of the symphysis. In total, 12 neonatal New Zealand White rabbits underwent pubic symphysiotomy (experimental group, n=9) or sham surgery (control group, n=3) on days 3 or 4 of life. Rabbits were scanned with cone-beam computed tomography at 1, 4, 12, and 20 weeks postoperatively to monitor changes in the following pelvic parameters, which are known to be altered in CBE: anterior segment angle, anterior segment length, intertriradiate distance, interpubic distance, and posterior segment angle. Changes within the experimental and control groups were evaluated using repeated-measures analysis of variance and post hoc Tukey honest significant difference testing. Two-tailed t tests were used to compare treatment groups at each time point. Both groups showed increases in anterior segment length and intertriradiate distance during the study period; rabbits in the experimental group also showed a steady increase in interpubic distance (F=43.9; P<0.001). Experimental rabbits had significantly larger mean values for anterior segment angle, intertriradiate distance, interpubic distance, and posterior segment angle than did control rabbits at all time points. We found no difference in mean anterior segment length between control and experimental groups at any time point. The difference in interpubic distance was particularly pronounced by 20 weeks (experimental group, 13±2.7 mm; control group, 1.1±0.1 mm; P<0.001). The pubic symphysis is essential for normal pelvic development. Its absence led to early pelvic angulation and progressive pubic separation in a rabbit model. However, we found no significant difference in the mean anterior segment length, and it is likely that other factors are also implicated in the growth disturbance seen in CBE. Level V.


Productive activities and development of frailty in older adults.
Our aim was to examine whether engagement in productive activities, including volunteering, paid work, and childcare, protects older adults against the development of geriatric frailty. Data from the first (1988) and second (1991) waves of the MacArthur Study of Successful Aging, a prospective cohort study of high-functioning older adults aged 70-79 years (n = 1,072), was used to examine the hypothesis that engagement in productive activities is associated with lower levels of frailty 3 years later. Engagement in productive activities at baseline was associated with a lower cumulative odds of frailty 3 years later in unadjusted models (odds ratio [OR] = 0.74, 95% confidence interval [CI] = 0.58-0.96) but not after adjusting for age, disability, and cognitive function (adjusted OR = 0.78, 95% CI = 0.60-1.01). Examination of productive activity domains showed that volunteering (but neither paid work nor childcare) was associated with a lower cumulative odds of frailty after adjusting for age, disability, and cognitive function. This relationship diminished and was no longer statistically significant after adjusting for personal mastery and religious service attendance. Though high-functioning older adults who participate in productive activities are less likely to become frail, after adjusting for age, disability, and cognitive function, only volunteering is associated with a lower cumulative odds of frailty.


Antiarrhythmic therapy in patients with congestive heart failure.
Current information suggests that in patients with congestive heart failure (CHF) who have asymptomatic ventricular arrhythmias, coronary artery disease (dilated ischemic cardiomyopathy), and a positive signal-averaged electrocardiogram, electrophysiologic studies are useful for stratifying risk and guiding therapy. Therapy with amiodarone hydrochloride (Cordarone) appears to improve survival in patients after myocardial infarction. In CHF patients with asymptomatic ventricular arrhythmias and dilated nonischemic cardiomyopathy, electrophysiologic studies are of little value in risk stratification because of their low yield of sustained monomorphic tachycardias. There is little evidence that therapy with conventional antiarrhythmic agents improves survival. Although amiodarone can suppress ventricular ectopic beats, no trial yet conducted has detected an effect on mortality. Randomized, controlled trials with low-dose amiodarone are needed for more definitive information. Most symptomatic patients should undergo electrophysiologic testing and receive guided therapy, either with antiarrhythmic drugs or with an implantable cardioverter-defibrillator.


Harnessing mtDNA variation to resolve ambiguity in 'Redfish' sold in Europe.
Morphology-based identification of North Atlantic Sebastes has long been controversial and misidentification may produce misleading data, with cascading consequences that negatively affect fisheries management and seafood labelling. North Atlantic Sebastes comprises of four species, commonly known as 'redfish', but little is known about the number, identity and labelling accuracy of redfish species sold across Europe. We used a molecular approach to identify redfish species from 'blind' specimens to evaluate the performance of the Barcode of Life (BOLD) and Genbank databases, as well as carrying out a market product accuracy survey from retailers across Europe. The conventional BOLD approach proved ambiguous, and phylogenetic analysis based on mtDNA control region sequences provided a higher resolution for species identification. By sampling market products from four countries, we found the presence of two species of redfish (S. norvegicus and S. mentella) and one unidentified Pacific rockfish marketed in Europe. Furthermore, public databases revealed the existence of inaccurate reference sequences, likely stemming from species misidentification from previous studies, which currently hinders the efficacy of DNA methods for the identification of Sebastes market samples.


Activity monitoring of functional OprM using a biomimetic microfluidic device.
This paper describes the fabrication and use of a biomimetic microfluidic device for the monitoring of a functional porin reconstituted within a miniaturized suspended artificial bilayer lipid membrane (BLM). Such a microfluidic device allows for (1) fluidic and electrical access to both sides of the BLM and (2) reproducible membrane protein insertion and long-term electrical monitoring of its conductance (G(i)), thanks to the miniaturization of the BLM. We demonstrate here for the first time the feasibility to insert a large trans-membrane protein through its β-barrel, and monitor its functional activity for more than 1 hour (limited by buffer evaporation). In this paper, we specifically used our device for the monitoring of OprM, a bacterial efflux channel involved in the multidrug resistance of the bacteria Pseudomonas aeruginosa. Sub-steps of the OprM channel conductance were detected during the electrical recordings within our device, which might be due to oscillations between several structural conformations (sub-states) adopted by the protein, as part of its opening mechanism. This work is a first step towards the establishment of a genuine platform dedicated to the investigation of bacterial proteins under reconstituted conditions, a very promising tool for the screening of new inhibitors against bacterial channels involved in drug resistance.


Tuberculous peritonitis masquerading as carcinomatosis.
Tuberculous peritonitis may debut with unspecific symptoms that can pose a diagnostic challenge for clinicians. We present a patient with tuberculous peritonitis masquerading as carcinomatosis. High clinical suspicion, appropriate identification of bacterial isolates of the Mycobacterium tuberculosis complex, and susceptibility testing are crucial to select target therapy.


[Metabolic disturbances in liver cirrhosis (part 2), hepatogenous diabetes: diagnostic aspects and treatment].
Uip to 20% of patients with liver cirrhosis develop hepatogenous diabetesdue to the hepatocellular functional loss and insulin resistance. Optimizing diabetic metabolic conditions is not only important to avoid typical late complications of diabetes, but also cirrhosis-associated complications e.g. gastrointestinal bleeding, hepatic encephalopathy or the occurence of hepatocellular carcinoma. So far there have beenno recommendations orguidelines for the diagnosis and treatmentof hepatogenous diabetes. The medical teatment of a diabetic condition is mainly influenced by its side effects. The risk of hypoglycemia must be considered carefully during drug treatment, especially in patients with chronic alcohol abuse. Suitable oral antidiabetics are glinides and short-acting sulfonylureas or possibly meal-related insulin administration with short-acting insulins or rapid-acting insulin analogues. Biguanide and PPAR-gamma agonists are contraindicated because of side effects in liver cirrhosis. Regarding basic treatment, an adequate daily energy and protein supply should be ensuredbecause the majority of patients with liver cirrhosis are malnourished.


Surface aspects of the developing human organ of Corti.
Thirteen cochleas from human fetuses ranging in age from week 9 to week 22 were observed by scanning electron microscopy. The classical 'base-to-apex' and 'internal-to-external' gradients of maturation were confirmed by surface observations of the developing organ of Corti. The tectorial membrane begins to be secreted around week 9, i.e. 2 weeks before the onset of the ciliogenesis. Its structure appears to be first amorphous and then fibrillar. The surface of the organ of Corti looks mature around week 22, but, in fact, its complete maturation, especially at outer hair cell level, probably occurs during the last trimester of pregnancy.


The Prevalence of Magnetic Resonance Imaging Hyperintensity in Migraine Patients and Its Association with Migraine Headache Characteristics and Cardiovascular Risk Factors.
To determine the frequency of hyperintense foci in migraine patients and the relationship with migraine headache characteristics and cardiovascular risk factors. Ninety patients with migraine headache (70 without aura and 20 with aura) were enrolled and interviewed. Information on their headache (severity, frequency, and mean disease duration) and other related data was obtained by completing a clinical checklist. Subsequently, brain magnetic resonance imaging (MRI) was performed and each patient was then evaluated for hyperintense lesions. Of the 90 patients, 29 (32%) had silent hyperintense lesions on their MRI. The mean age of the patients with hyperintense foci was 41 years while those with no lesions was 33 years (p<0.010). Supratentorial hyperintense lesions represented the majority of lesions in the patients (n=46, 63%). Moreover, 56.3% of the lesions (n=41) were located within the right hemisphere. Cardiovascular risk factors such as smoking, serum cholesterol, oral contraceptive pills use, and body mass index (BMI) were not significantly different in these two groups (p>0.050). The lesions were found significantly more frequently in the patients who experienced chronic migraine (p=0.032). Our study adds weight to the theory that disease duration has a key role in the formation of hyperintense brain lesions. Certain cardiovascular risk factors such as sex, smoking, serum cholesterol, and BMI, do not affect the presence or absence of such lesions, suggesting that the relationship between migraine and these lesions may be directly due to the effects of migraine itself.


Rheological Behavior of Amino-Functionalized Multi-Walled Carbon Nanotube/Polyacrylonitrile Concentrated Solutions and Crystal Structure of Composite Fibers.
The rheological behavior of amino-functionalized multi-walled carbon nanotubes (amino-CNTs)/polyacrylonitrile (PAN) concentrated solutions in the dimethyl sulphoxide solvent and the effects of the amino-CNTs on the PAN precursor fibers by wet-spinning method were investigated. The amino-CNT/PAN concentrated solutions prepared by in situ solution polymerization with homogeneous dispersion of amino-CNTs have higher complex viscosity, storage modulus and loss modulus as compared to the control PAN concentrated solutions containing 22% PAN polymer by mass. The composite fibers with amino-CNTs of 1 wt % have lower degree of crystallization, crystal size and crystal region orientation compared to the control PAN precursor fibers. However, the amino-CNT/PAN composite fibers with diameter of about 10.5 μm exhibit higher mechanical properties than the control PAN precursor fibers with diameter of about 8.0 μm. Differential scanning calorimetry analysis demonstrated that the cyclization reaction in composite fibers have broad exothermic temperature range and low exothermic rate. These results indicate that the addition of amino-CNTs into PAN precursor fibers is beneficial to controlling the process of thermal stabilization and obtaining the higher performance of composite fibers.


Ionic conductivity and mixed-ion effect in mixed alkali metaphosphate glasses.
In this work, mixed alkali metaphosphate glasses based on K-Na, Rb-Na, Rb-Li, Cs-Na and Cs-Li combinations were studied by differential scanning calorimetry (DSC), complex impedance spectroscopy, and Raman spectroscopy. DSC analyses show that both the glass transition (Tg) and melting temperatures (Tm) exhibit a clear mixed-ion effect. The ionic conductivity shows a strong mixed-ion effect and decreases by more than six orders of magnitude at room temperature for Rb-Na or Cs-Li alkali pairs. This study confirms that the mixed-ion effect may be explained as a natural consequence of random ion mixing because ion transport is favoured between well-matched energy sites and is impeded due to the structural mismatch between neighbouring sites for dissimilar ions.


Complete nucleotide sequence of clover yellow mosaic virus RNA.
The entire genomic RNA of clover yellow mosaic virus was sequenced from cDNA clones and run-off cDNA transcripts. The genomic RNA is 7015 nucleotides in length [excluding a 3' poly(A) tail], with six open reading frames (ORFs) greater than 150 nucleotides in length. The first five ORFs encode proteins of Mr 191K, 26K, 12K, 6.5K and 28K, respectively. The sixth ORF lies completely within ORF1 and codes for a protein of Mr 14K. The capsid protein coding region (Mr 23K) is found within ORF5 which encodes the Mr 28K protein. Proteins encoded by ORFs 1 to 3 and ORF5 show strong homology with proteins of other potexviruses, especially papaya mosaic virus.


Microencapsulated linear polymers: "soluble" heterogeneous catalysts.
A new strategy for supporting catalysts based on the microencapsulation of linear polymers is presented. In this paper, we present a DMAP capsule that is capable of catalyzing acylation reactions. The catalyst is compared to DMAP on cross-linked and linear polystyrene, as well as small molecule DMAP. Rapid optimization through modification of encapsulation conditions is demonstrated. The optimization provides a dynamic range of catalysis from 90 to 300% of the rate of DMAP on polystyrene.


Ca2+ dependency of diadenosine 5',5"'-p1,p4-tetraphosphate degradation in dog plasma.
Diadenosine 5',5"'-p1,p4-tetraphosphate (Ap4A) degradation in dog plasma was inhibited by the addition of EDTA. The Ap4A degrading activity seemed to be recovered by the addition of metal ions, Ca2+, Co2+, Cu2+, Mg2+, Mn2+ or Zn2+ to plasma in which the activity was lost by the addition of EDTA. Especially, the degradation was accelerated by the addition of Ca2+ to the plasma, and the degradation rate was dependent on the concentration of Ca2+. The results of this study suggested that the enzymatic degradation of Ap4A in dog plasma was modulated by the concentration of Ca2+.


[Radionuclide studies of atherosclerosis].
New Tc-99m-labeled brain perfusion imaging agents, such as Tc-99m-HMPAO, and Tc-99m-ECD, are developed and expected to improve the clinical study of cerebral perfusion disturbance due to arteriosclerosis. They enable us better images than I-123-IMP and more accurate diagnosis. Similarly, in the field of cardiovascular nuclear medicine, new Tc-99m-labeled compounds, Tc-99m-MIBI, Teboroxime and Tetrofosmin are available. Furthermore, I-123-MIBG, a tracer taken up in presynaptic adrenergic vesicles, and I-123-BMIPP, a new agent developed for the evaluation myocardial fatty acid metabolism, will mark a new epoch in the study of coronary sclerosis. In order to image atherosclerosis directly, In-111-polyclonal immunoglobulin G, Tc-99m-low density lipoprotein etc., are under investigation.


Reciprocal rewards: British Poor Law nursing and the campaign for state registration.
In the pages of her publications 'The Nursing Record' and 'The British Journal of Nursing', Mrs Bedford Fenwick portrayed the Poor Law nurses as struggling against the forces of parsimony and ignorance in the persons of the workhouse master and matron. The representation of these women as victims of the system rescued by Mrs Bedford Fenwick disguises their considerable achievements towards improving the quality of care for their deprived patients. This paper examines how the Poor Law nurses seized the opportunity afforded by the campaign for State Registration to further their cause in developing a professional nursing service for a neglected group of patients.


Proteome identification of binding-partners interacting with cell polarity protein Par3 in Jurkat cells.
The evolutionarily conserved cell polarity protein Par3, a scaffold-like PDZ-containing protein, plays a critical role in the establishment and maintenance of epithelial cell polarity. Although the role of Par3 in establishing cell polarity in epithelial cells has been intensively explored, the function of Par3 in hematopoietic cells remains elusive. To address this issue, we generated GST-fusion proteins of Par3 PDZ domains. By combining the GST-pull-down approach with liquid chromatography-tandem mass spectrometry, we identified 10 potential novel binding proteins of PDZ domains of Par3 in Jurkat cells (a T-cell line). The interaction of Par3 with three proteins--nuclear transport protein importin-alpha4 and proteasome activators PA28beta and PA28gamma--was confirmed using in vitro binding assay, co-immunoprecipitation assay and immunofluorescence microscopy. Our results have the potential to uncover novel functions of the cell polarity protein Par3 in blood cells.


Back to the future: surgical rehearsal platform technology as a means to improve surgeon-patient alliance, patient satisfaction, and resident experience.
Informed consent, when performed appropriately, serves many roles beyond simply obtaining the prerequisite medicolegal paperwork to perform a surgery. Prior studies have suggested that patient understanding is poor when verbal communication is the sole means of education. Virtual reality platforms have proven effective in enhancing medical education. No studies exist that have demonstrated the utility of virtual reality-facilitated informed consent (VR-IC) in improving the physician-patient alliance. The aim of this study was to determine the utility of VR-IC among patients providing consent for surgery and the impact of this educational and information technology-based strategy on enhancing the physician-patient alliance, patient satisfaction, and resident-physician perception of the consent process. Prospective, single-site, pre- and postconsent surveys were administered to assess patient and resident perception of informed consent performed with the aid of VR-IC at a large tertiary academic medical center in the US. Participants were adult patients (n = 50) undergoing elective surgery for tumor resection and neurosurgical residents (n = 19) who obtained patient informed consent for these surgical procedures. Outcome measures included scores on the Patient-Doctor Relationship Questionnaire (PDRQ-9), the modified Satisfaction with Simulation Experience Scale, and the Maslach Burnout Inventory. Patient pre- and postconsent data were recorded in real time using a secure online research data platform (REDCap). A total of 48 patients and 2 family members provided consent using VR-IC and completed the surveys pre- and postconsent; 47.9% of patients were women. The mean patient age was 57.5 years. There was a statistically significant improvement from pre- to post-VR-IC consent in patient satisfaction scores. Measures of patient-physician alliance, trust, and understanding of their illness all increased. Among the 19 trainees, perceived comfort and preparedness with the informed consent process significantly improved. VR-IC led to improved patient satisfaction, patient-physician alliance, and patient understanding of their illness as measured by the PDRQ-9. Using VR-IC contributed to residents' increased comfort in the consent-gathering process and handling patient questions. In an era in which satisfaction scores are directly linked with hospital and service-line outcomes and reimbursement, positive results from VR-IC may augment physician and hospital satisfaction scores in addition to increasing measures of trust between physicians and patients.


[Relationship between changes in the prevalence of HIV infection in pregnant women from 2006 to 2015 and place of residence in Benin].
We aimed to determine the relationship between changes in the prevalence of HIV infection in pregnant women from 2006 to 2015 and place of residence in Benin. In a retrospective and analytical study, were viewed the reports of the annual surveys of HIV infection among pregnant women from 2006 to 2015 across the country. A total of 138,319 pregnant women participated in the annual HIV surveys from 2006 to 2015. The national prevalence of HIV infection among pregnant women between 2006 and 2015 was 2%. The prevalence of HIV infection from 2006 to 2015 in pregnant women increased significantly in departments of Mono (p = 0.001) and Donga (p = 0.001) and decreased in the departments of Collines (p = 0.000) and Couffo (p = 0.001) and in urban areas (p = 0.000). Changes in the prevalence of HIV infection among pregnant women between 2006 and 2015 varied across departments and according the urbanization of the residence. The National AIDS control program may take these results into account when planning interventions against HIV for optimal response against the pandemic infection.


Design of a novel affinity probe using the cell wall-binding domain of a Listeria monocytogenes autolysin for pathogen detection.
Human listeriosis is caused by consuming foods contaminated with the bacterial pathogen Listeria monocytogenes, leading to the development of a severe and life-threatening foodborne illness. Detection of L. monocytogenes present in food and food processing environments is crucial for preventing Listeria infection. The L. monocytogenes peptidoglycan hydrolase IspC anchors non-covalently to the bacterial surface through its C-terminal cell wall-binding domain (CWBD), CWBDIspC. This study explored the surface binding property of CWBDIspC to design, construct, characterize, and assess an affinity molecular probe for detecting L. monocytogenes. CWBDIspC recognized a cell wall ligand lipoteichoic acid that remains evenly displayed and mostly unoccupied on the bacterial surface for interaction with the exogenously added CWBDIspC. CWBDIspC, when fused to the enhanced green fluorescent protein reporter or covalently conjugated onto magnetic beads, exhibited the functionality as an antibody alternative for rapid detection and efficient separation of the pathogen.


Shark-related injuries in Hawai'i treated at a level 1 trauma center.
Although rare, human-shark interactions can result in a wide spectrum of injuries. This is the first study to characterize shark-related injuries (SRIs) in Hawai'i. This is a retrospective review of the State of Hawai'i Division of Aquatic Resources Shark Incidents List between January 1, 2009 and December 31, 2019. Trauma registry data and medical records of patients treated for SRIs at the only level 1 trauma center in Hawai'i were reviewed. Sixty-one patients sustained SRIs in the Hawaiian Islands: 25 in Maui, 16 in O'ahu, 12 in Hawai'i, and 8 in Kaua'i. In cases where the shark species could be identified, tiger sharks were the most frequent (25, 41%). Four cases were fatal-all died on scene in Maui with the shark species unknown. Forty-five survivors (79%) received definitive care at regional facilities. Twelve (21%) were treated at the level 1 trauma center, of which two were transferred in for higher level of care. Of the 12 patients, 11 (92%) had extremity injuries, with 3 lower extremity amputations (25%), 2 with vascular injuries (17%), and 5 with nerve injuries (42%). One had an injury to the abdomen. All patients had local bleeding control in the prehospital setting, with 9 (75%) tourniquets and 3 (25%) hemostatic/pressure dressings applied for truncal or proximal extremity injuries. The mean time from injury to emergency department arrival was 63 minutes. Most SRIs are managed at regional facilities, rather than at a level 1 trauma center. Prehospital hemorrhage control is an important survival skill as time to definitive care may be prolonged. For cases treated at the level 1 trauma center, nerve injuries were common and should be suspected even in the absence of major vascular injury. Correlating shark behavior with observed injury patterns may help improve public awareness and ocean safety. Level V, epidemiological.


Determination of the Maximum Velocity of Filaments in the in vitro Motility Assay.
The in vitro motility assay (IVMA) is a powerful tool commonly used in basic muscle research and for drug screenings with the aim to find treatment options for neuromuscular disorders. In brief, the sliding movement of fluorescence-labeled actin filaments on myosin motor proteins is recorded, and the sliding velocity is analyzed via image analysis methods. Due to low signal-to-noise ratios and large variability in the velocity signal, accurate determination of the maximum sliding velocity is challenging. We introduce a new method and software program named Actin Phase Velocity (ActiPHV). The method extracts the maximum velocity from filament tracking data. Based on simulated and real reference data we show that our method yields a higher accuracy compared to previous methods. As a result, our method enables enhancing the sensitivity of the IVMA to better exploit its full potential.


Hybrid dysgenesis in Drosophila melanogaster: a new type of gonadal dysgenic sterility expressed at the pre-pupal stage.
Two sublines, B-202 and B-207, which were derived from crosses between Or-R (M) females and Cy/Pm (P) males were found to cause a new type of gonadal dysgenic sterility, designated as the GD-3. GD-3 sterility showed a typical reciprocal cross effect under the P-M system. It was caused at the frequency close to 100% in dysgenic offsprings reared above 25 degrees C, of which gonads were morphologically clearly different from those of usual GD sterility, whereas there was no indication of GD-3 sterility at temperatures below 24 degrees C. Temperature sensitive period of GD-3 sterility was estimated to the prepupal stage by shift-down experiment. In the B-202 subline, the 2nd chromosomes marked with Pm alone carried GD-3 elements. Those of the B-207 subline, however, were estimated to locate both on the 2nd and 3rd chromosomes, acting synergistically with each other.


Risk factors and their relation to initiation of alcohol use among early adolescents.
This study examined the relationship between risk factors and initiation of alcohol use over a 15-month period among a cohort of 7th graders who were abstainers at the time of initial testing. The relationship between risk factors and alcohol use was examined using a discriminant function analysis. At the univariate level, rejection of parental authority, deviant behavior, and sensation seeking were statistically significant. The discriminant function retained only three of the risk factors: rejection of parental authority, deviant behavior, and religious commitment. Implications for school-based prevention programs are discussed, particularly the need to target primary prevention programs based upon adolescents' risk.


Diagnosis, treatment, clinical course, and prognosis of childhood-onset craniopharyngioma patients.
For decades gross-total resection was the preferred treatment option in childhood-onset craniopharyngioma, assuming that radical strategies at the time of initial diagnosis and treatment would result in cure. Recent reports on long-term prognosis, novel treatment approaches, and molecular genetics provide new insights into more risk-adapted treatment strategies in order to prevent sequelae such as hypothalamic syndrome. A search for original articles published between 2000 and 2016 was performed in PubMed, Science Citation Index Expanded, EMBASE and Scopus. The search terms used were "craniopharyngioma", "hypothalamus", "pituitary", "obesity", "irradiation", and "neurosurgery". The clinical, neuroradiological and surgical definition of hypothalamic involvement is a fundamental factor related to postoperative poor outcome, progressive obesity and neuropsychological impairment after surgical removal. There is a need to change the previous "gold-standard" objective of a primary radical tumor removal in all cases by the new paradigm of a limited resection plus focused radiotherapy in patients with hypothalamic lesions. Hypothalamic involvement and treatment-related hypothalamic lesions are associated with the highest risk of postoperative sequelae. Three dimensional intensity modulated proton beam radiotherapy has potential advantage of over photon beam methods to focus and limit the radiation effects to optic and hypothalamic structures. Preclinical, in vivo mouse models of craniopharyngioma have potential advantage to investigate molecular pathways deregulated in the tumor and to test the use of specific drugs. As expertise has been shown to have impact on post-treatment morbidity, medical societies should establish criteria of adequate professional expertise for the treatment of craniopharyngioma.


A threshold model of social support, adjustment, and distress after breast cancer treatment.
This study examined a threshold model that proposes that social support exhibits a curvilinear association with adjustment and distress, such that support in excess of a critical threshold level has decreasing incremental benefits. Women diagnosed with a first occurrence of breast cancer (N = 154) completed survey measures of perceived support (Social Provisions Scale), quality of life (Functional Living Index--Cancer), adjustment (Psychological Adjustment to Illness Scale) and psychological distress (Brief Symptom Inventory) approximately 3 weeks after surgical treatment and 8-16 months later. Consistent with a threshold model, multiple regression analyses suggested a significant curvilinear relationship between social support and distress at Time 1 and Time 2 and between social support and adjustment at Time 2. Consistent with this model, the significant bivariate correlations between social support and outcomes were accounted for almost entirely by women in the lowest quartile of support. Social support among women in the highest 3 quartiles was unrelated or only marginally related to adjustment and distress.


Allogeneic bone marrow transplantation for patients with hematologic malignancies.
Allogeneic marrow transplantation is an effective modality for the treatment of patients with hematologic malignancies. Limitations of success are donor availability, posttransplant relapses, and transplant-related morbidity and mortality. Progress is being made in improving the results of partially HLA matched family member donor transplants and in the use of HLA matched unrelated donors. Increases in dose intensity of pretransplant regimens are limited by toxicity and in order to be effective methods need to be developed to ameliorate side effects. The use of anti-inflammatory agents and recombinant growth factors show promise in decreasing transplant-related deaths.


Local release of human neutrophil lipocalin (HNL), IL-8, and TNF-alpha is decreased as response to topical prednisolone treatment in distal ulcerative colitis and proctitis.
The local release of human neutrophil lipocalin, considered to be highly specific for neutrophil granulocyte activation, and interleukin-8 and tumor necrosis factor-alpha were studied in 11 patients with distal ulcerative colitis and proctitis before and during treatment with steroid enemas. A rectal perfusion technique for sampling and specific immunoassays for analysis were used. In responders (N = 8) the concentrations of all proteins decreased during the study. There was a close correlation between human neutrophil lipocalin concentrations and treatment response. Tumor necrosis factor-alpha showed an initial decline in concentrations irrespective of treatment outcome and preceded the decline of human neutrophil lipocalin and interleukin-8. We conclude that decreased neutrophil degranulation is correlated with treatment outcome. Furthermore, an important role of tumor necrosis factor-alpha in the process of stimulating neutrophil activation and degranulation in ulcerative colitis is suggested.


Use of minigene systems to dissect alternative splicing elements.
Pre-mRNA splicing is an essential step for gene expression in higher eukaryotes. The splicing efficiency of individual exons is determined by multiple features involving gene architecture, a variety of cis-acting elements within the exons and flanking introns, and interactions with components of the basal splicing machinery (called the spliceosome) and auxiliary regulatory factors which transiently co-assemble with the spliceosome. Both alternative and constitutive exons are recognized by multiple weak protein:RNA interactions and different exons differ in the interactions which are determinative for exon usage. Alternative exons are often regulated according to cell-specific patterns and regulation is mediated by specific sets of cis-acting elements and trans-acting factors. Transient expression of minigenes is a commonly used in vivo assay to identify the intrinsic features of a gene that control exon usage, identify specific cis-acting elements that control usage of constitutive and alternative exons, identify cis-acting elements that control cell-specific usage of alternative exons, and once regulatory elements have been identified, to identify the trans-acting factors that bind to these elements and modulate splicing. This chapter describes approaches and strategies for using minigenes to define the cis-acting elements that determine splice site usage and to identify and characterize the trans-acting factors that bind to these elements and regulate alternative splicing.


[Involvement of the shoulder in rheumatoid arthritis].
The course of rheumatoid arthritis (R.A.) in the shoulder is evaluated in 100 patients in a retrospective study and in 73 patients in a prospective study. The involvement of the shoulder may occur at an early stage of the disease. However, usually it causes a significant handicap at a later stage. The retrospective study shows that 62% of the patients hospitalized between 1976 and 1992 for R.A. complained of pain, reduction in range of motion and functional disability of one or both shoulders. However, these historic cases cannot be used for a radiological study because the shoulders have been radiographed in 17% of cases only, probably because of the poor possibilities of surgical therapies available at this time. The survey of 72 patients received at the out- patient clinic between september 1992 and december 1993 who had a radiograph of the shoulder is the basis for the description of the progress of the disease. The erosions appear at the border of the cartilage where the synovium is attached and refers mainly to the cephalic articular cartilage. Narrowing of the subacromial space is often present with early appearance of subluxation in the cranial direction. The destruction often prevails in the area of humeral head but cases with predominant global joint space narrowing or with destruction of glenoid labrum and fossa exist as well. Secondary osteoarthritis was often observed. The involvement of the shoulders is not always symmetric. Unilateral involvement has been observed. The different evolutive processes will be illustrated and their frequency evaluated. The forms with predominant cephalic destruction constitute the best indications for total shoulder arthroplasty.


Epigenetics: an emerging technology in the diagnosis and treatment of cancer.
Transcriptional silencing resulting from changes in epigenetic regulation of gene expression is the most frequent mechanism by which tumor suppressor genes are inactivated in human cancer. Genes participating in numerous functional groups and pathways leading to malignancy are subject to aberrant CpG methylation, with associated downregulation of expression, in human carcinogenesis. Methylation profiling can identify distinct subtypes of common human cancers and may have utility in predicting clinical phenotypes in individual patients, including sensitivity to chemotherapeutic agents. Hypomethylating agents have clinical activity in some hematological malignancies, and there is accumulating evidence correlating clinical response with demethylation and concomitant reactivation of expression of specific target genes. Epigenetic analysis is likely to have an increasingly important part to play in the diagnosis, prognostic assessment and treatment of malignant disease.


Dynamic CT in pancreatic lymphoma.
We retrospectively reviewed the dynamic CT examinations of eight patients with pancreatic lymphoma. Four tumors were rounded masses with well-defined contours, four were more infiltrating lesions. The median cross-sectional diameter of the tumors was 6 cm (range 2.5-12 cm). At dynamic CT, the tumors were hypodense (n = 8) and somewhat heterogeneous (n = 6). Additional features were enlarged lymph nodes, 1-3 cm in diameter (n = 5), dilatation of the biliary tract and pancreatic duct (n = 5), abnormalities in the fat around the celiac trunk and/or the superior mesenteric artery (n = 4), and venous stenosis or occlusion (n = 7). The CT findings of pancreatic lymphoma are more various than has been previously reported. Findings such as small tumor size, well-defined contours, tumor heterogeneity, pancreatic duct dilatation, and venous invasion may be seen. Pancreatic lymphoma cannot be reliably distinguished from pancreatic carcinoma by CT findings alone.


Findings of biopsy-proven chronicity and end-stage renal failure associated with oral sodium phosphate solution.
Bowel purgatives containing oral sodium phosphate (OSP) solution are used frequently in general practice and they have the potential of causing acute kidney injury especially in patients with some identified risk factors. Kidney injury may lead to chronicity and end-stage renal disease. Here we present, with renal biopsy findings, an elderly patient suffering from end-stage renal failure due to OSP solution.


Setting goals for drug policy: harm reduction or use reduction?
Historically, United States drug policy has focused on use reduction; harm reduction is a prominent alternative. This paper aims to provoke and inform more debate about the relative merits of these two. Since harm is not necessarily proportional to use, use reduction and harm reduction differ. Both terms are somewhat ambiguous; precisely defining them clarifies thinking and policy implications. Measures associated with use reduction goals are poor; those associated with harm reduction are even worse. National goals influence the many decentralized individuals who collectively make drug policy; clearly enunciating goals makes some policy choices transparent and goals serve a variety of purposes besides guiding programmatic decisions. We recommend that the overall objective be to minimize the total harm associated with drug production, distribution, consumption and control. Reducing use should be seen as a principal means of attaining that end.


Taste aversion after ingestion of lithium chloride: an associative analysis.
In five experiments with rats we examined the aversion established by consumption of a solution of lithium chloride (LiCl). Experiment 1 showed that consumption of LiCl established an aversion to saline (NaCl). Experiment 2 showed that the size of the aversion was reduced in rats given pre-exposure to saline (a latent inhibition effect). Experiment 3 showed that experience of a sucrose-saline compound prior to consumption of LiCl generated an aversion to sucrose (a sensory preconditioning effect). Experiments 4 and 5 examined the effects produced by consumption of a sucrose-LiCl compound and demonstrated reciprocal overshadowing between the two tastes. These results confirm that consumption of LiCl establishes an aversion to the taste of this substance. Their implications for the use of orally consumed LiCl as a technique for the control of predatory behaviour are discussed.


Sodium Incorporation for Enhanced Performance of Two-Dimensional Sn-Based Perovskite Transistors.
Two-dimensional metal halide perovskites (2D MHPs) are promising candidates for transistor channel materials because of their high mobility in the lateral direction; however, Sn-based 2D MHPs exhibit poor film quality and oxidation stability. Here, we report a simple method to improve the performance and stability of 2D MHP transistors by incorporating sodium iodide (NaI) additives. By adding 1 vol % NaI (Na1), the transistors with phenethylammonium tin iodide (PEA2SnI4) exhibited reduced dual-sweep hysteresis, robust bias stability, and larger hole mobility (2.13 cm2 V-1 s-1) than that of a pristine device (0.39 cm2 V-1 s-1). Improvements in the film quality, such as increased grain size, crystallinity, and better film coverage, were observed in the PEA2SnI4:NaI film. In addition, NaI effectively passivated the iodine vacancies at the grain boundaries, thereby suppressing the defects.


Transgender Children: Conundrums and Controversies--A Introduction to the Section.
This paper introduces the readership of The Psychoanalytic Study of the Child to the topic of transgender children, which will be investigated in the papers that follow. A flashpoint in the recent discourse that escorts children who self-describe as gender nonconforming is whether or not to support the practice of the medical suspension of puberty of these children by the administration of hormonal treatment. Relevant up-to-date research findings on this subject will be reviewed here. Despite those advocates and opponents who swarm around both poles, any reliable conclusions as to the long-term safety and psychological effects of puberty suppressants will remain provisional untilfuture studies proffer more definitive answers. While we await further study, the journal sees the necessity to press for dialogue concerning this conundrum. Anchoring this section is a clinical paper by Diane Ehrensaft, Ph.D., which documents the psychotherapeutic treatment of a transgender child who was prescribed puberty suppressants. The commentaries that follow and that are briefly summarized in this introduction will accent the psychoanalytic developmental point of view. This will provide the principal framework for the study of this controversy, which underscores the complementary dimensions of linear and nonlinear progressive hierarchical growth. In this context, features such as the developmentally normative fluidity of self-structures, including gender role identity, and the evolution of concrete thinking toward metaphoricity and figurative meaning-making in middle childhood and adolescence will be examined and applied to the clinical data. In addition, the argument that the use of puberty suppressants exacts a premature foreclosure on the reorganizing potential of developmental growth, and the proposed efftcts of the crosscurrents of the sociocultural body politic on these children and on the decision to opt for the suspension of pubertal growth will be explored.


Spontaneous Coronary Artery Dissection: Does Being Unemployed Matter? Insights from the GSCAD Registry.
Spontaneous coronary artery dissection (SCAD) has emerged as an important cause of acute coronary syndrome (ACS) and sudden cardiac death. Physical or emotional stressors are the most commonly reported triggers for SCAD. Unemployment has been identified as a source of emotional stress and is linked to poor mental and physical health. To examine the association between employment status and in-hospital and follow-up adverse cardiovascular events in patients with SCAD. We conducted a retrospective, multi-center, observational study of patients undergoing coronary angiography for ACS between January 2011 and December 2017. The total number of patients enrolled was 198,000. Patients were diagnosed with SCAD based on angiographic and intravascular imaging modalities whenever available. There were 83 patients identified with SCAD from 30 medical centers in 4 Arab gulf countries. In-hospital (myocardial infarction, percutaneous intervention, ventricular tachycardia/ventricular fibrillation, cardiogenic shock, death, internal cardioverter/ defibrillator placement, dissection extension) and follow-up (myocardial infarction, de novo SCAD, death, spontaneous superior mesenteric artery dissection) cardiac events were compared among those who were employed and those who were not. The median age of patients in the study was 44 (37- 55) years. There were 42 (50.6%) female patients, and 41 (49.4) male patients. Of the cohort, 50 (60%) of the patients were employed and the remaining 33 (40%) were unemployed. 66% of all men were employed and 76% of all women were unemployed. After adjusting for gender unemployment was associated with worse in- -hospital and follow-up cardiac events (adjusted OR 7.1, [1.3, 37.9]), p = 0.021. Adverse cardiovascular events were significantly worse for patients with SCAD who were unemployed.


Integrating abiotic chemical catalysis and enzymatic catalysis in living cells.
Life emerges from networks of multiple chemical reactions mediated by enzymes. If abiotic chemical catalysis is implanted into the reaction network of life, such an integration would produce organisms generating unique secondary metabolites and value-added materials from feedstocks or even air, or new diagnostics and therapeutics against diseases. In this review, we introduce selected papers in this emerging field of catalysis research.


Helix Electrohydrodynamic Printing of Highly Aligned Serpentine Micro/Nanofibers.
Micro/nano serpentine structures have widespread applications in flexible/stretchable electronics; however, challenges still exist for low-cost, high-efficiency and controllable manufacturing. Helix electrohydrodynamic printing (HE-printing) has been proposed here to realize controllable direct-writing of large area, highly aligned serpentine micro/nanofibers by introducing the rope coiling effect into printing process. By manipulating the flying trajectory and solidification degree of the micro/nano jet, the solidified micro/nanofiber flying in a stabilized helical manner and versatile serpentine structures deposited on a moving collector have been achieved. Systematic experiments and theoretical analysis were conducted to study the transformation behavior and the size changing rules for various deposited microstructures, and highly aligned serpentine microfibers were directly written by controlling the applied voltage, nozzle-to-collector distance and collector velocity. Furthermore, a hyper-stretchable piezoelectric device that can detect stretching, bending and pressure has been successfully fabricated using the printed serpentine micro/nanofibers, demonstrating the potential of HE-printing in stretchable electronics manufacturing.


An in vitro and molecular informatics study to evaluate the antioxidative and β-hydroxy-β-methylglutaryl-CoA reductase inhibitory property of Ficus virens Ait.
The present study is initially intended to evaluate antioxidant and β-hydroxy-β-methylglutaryl-CoA reductase (HMGR) inhibitory property of Ficus virens Ait., first by in vitro analyses followed by a corroboratory molecular informatics study. Our results show that of all the sequentially extracted fraction of F. virens bark and leaves extract, F. virens bark methanol extract exhibits strong radical scavenging, antioxidant and oxidative DNA damage protective activity, which is well correlated with its total phenolic content. In addition, F. virens bark methanol extract, which is non-cytotoxic, significantly and non-covalently inhibit the HMGR activity (IC50 = 3.45 ± 0.45 µg/ml) in comparison with other extracts. The mechanistic aspect of this inhibition activity is authenticated by molecular docking study of bioactive compounds as revealed from gas chromatography-mass spectrometry data, with HMGR. The analysis for the first time indicates that quinic acid (ΔG: -8.11 kcal/mol) and paravastatin (ΔG: -8.22 kcal/mol) exhibit almost same binding energy, while other compounds also showed good binding energy, suggesting that quinic acid alone or in combination with other major bioactive compound is probably responsible for HMGR inhibitory property of the extract and plausibly can be used in in vivo system for the management, prevention, and alleviation of hypercholesterolemia as well as hypercholesterolemia-induced oxidative stress.


Comparison of proteins of simian herpesvirus aotus type 2 and bovine herpesvirus type 4.
Genomes of herpesvirus aotus type 2 (HVA-2) and bovine herpesvirus type 4 (BHV-4) have previously been shown to be closely similar. Moreover, preliminary serological data indicated that HVA-2 is antigenically related to BHV-4. To extend this study, structural components of four BHV-4 strains and HVA-2 were compared by SDS-PAGE, radioimmunoprecipitation and Western blotting. The overall pattern of structural proteins was the same for HVA-2 and BHV-4 but variations were observed in electrophoretic profiles of glycoproteins, mainly of the two major ones (gp6/gp10/gp17 and gp11/VP24). Variations between HVA-2 and BHV-4 glycoproteins were greater than those observed among BHV-4 strains.


Mental health and substance use patterns associated with lifetime suicide attempt, incarceration, and homelessness: A latent class analysis of a nationally representative sample of U.S. veterans.
A substantial proportion of U.S. military veterans experience mental health and/or substance use disorders. As public awareness of these difficulties rises, so too does interest in the relation between veteran behavioral health and high-risk events, namely suicide attempts, incarceration, and homelessness. Using latent class analysis and a large, nationally representative sample of community veterans, the current study examined common patterns of veteran behavioral health disorders and the associations between these patterns and high-risk events. Results suggest four classes of veterans, including a "healthy" class (comprising 69% of the total sample), a "substance use disorder" class (16%), a "personality disorder-substance use disorder" class (8%), and a "depressive disorder" class (7%). Veterans in the healthy class had the lowest rates of suicide attempt (2%), incarceration (14%), and homelessness (3%), whereas veterans in the personality disorder-substance use disorder class had the highest rates of these events (27%, 45%, and 22%, respectively). Results attest to the importance of investing clinical resources into addressing the needs of veterans experiencing complex behavioral health patterns, particularly personality and substance use disorders. Implications for the health care of veterans are discussed. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Microbiome remodeling through bacterial competition and host behavior enables rapid adaptation to environmental toxins.
Human activity is altering the environment in a rapid pace, challenging the adaptive capacities of genetic variation within animal populations. Animals also harbor extensive gut microbiomes, which play diverse roles in host health and fitness and may help expanding host capabilities. The unprecedented scale of human usage of xenobiotics and contamination with environmental toxins describes one challenge against which bacteria with their immense biochemical diversity would be useful, by increasing detoxification capacities. To explore the potential of bacteria-assisted rapid adaptation, we used Caenorhabditis elegans worms harboring a defined microbiome, and neomycin as a model toxin, harmful for the worm host and neutralized to different extents by some microbiome members. Worms raised in the presence of neomycin showed delayed development and decreased survival but were protected when colonized by neomycin-resistant members of the microbiome. Two distinct mechanisms facilitated this protection: gut enrichment driven by altered bacterial competition for the strain best capable of modifying neomycin; and host avoidance behavior, which depended on the conserved JNK homolog KGB-1, enabling preference and acquisition of neomycin-protective bacteria. We further tested the consequences of adaptation, considering that enrichment for protective strains may represent dysbiosis. We found that neomycin-adapted gut microbiomes caused increased susceptibility to infection as well as an increase in gut lipid storage, suggesting metabolic remodeling. Our proof-of-concept experiments support the feasibility of bacteria-assisted host adaptation and suggest that it may be prevalent. The results also highlight trade-offs between toxin adaptation and other traits of fitness.


Rubyspira, new genus and two new species of bone-eating deep-sea snails with ancient habits.
Rubyspira, a new genus of deep-sea snails (Gastropoda: Abyssochrysoidea) with two living species, derives its nutrition from decomposing whalebones. Molecular phylogenetic and morphological evidence places the new genus in an exclusively deep-sea assemblage that includes several close relatives previously known as fossils associated with Cretaceous cold seeps, plesiosaur bones, and Eocene whalebones. The ability to exploit a variety of marine reducing environments may have contributed to the evolutionary longevity of this gastropod lineage.


Cardiac endothelial cells isolated from mouse heart - a novel model for radiobiology.
Cardiovascular disease is recognized as an important clinical problem in radiotherapy and radiation protection. However, only few radiobiological models relevant for assessment of cardiotoxic effects of ionizing radiation are available. Here we describe the isolation of mouse primary cardiac endothelial cells, a possible target for cardiotoxic effects of radiation. Cells isolated from hearts of juvenile mice were cultured and irradiated in vitro. In addition, cells isolated from hearts of locally irradiated adult animals (up to 6 days after irradiation) were tested. A dose-dependent formation of histone γH2A.X foci was observed after in vitro irradiation of cultured cells. However, such cells were resistant to radiation-induced apoptosis. Increased levels of actin stress fibres were observed in the cytoplasm of cardiac endothelial cells irradiated in vitro or isolated from irradiated animals. A high dose of 16 Gy did not increase permeability to Dextran in monolayers formed by endothelial cells. Up-regulated expression of Vcam1, Sele and Hsp70i genes was detected after irradiation in vitro and in cells isolated few days after irradiation in vivo. The increased level of actin stress fibres and enhanced expression of stress-response genes in irradiated endothelial cells are potentially involved in cardiotoxic effects of ionizing radiation.


Influence of stimulation train length on the opioid-induced inhibition of norepinephrine release in the rabbit ear artery.
In perfused segments of rabbit ear artery the effects of opioid agonists on vasoconstrictor responses to adrenergic nerve stimulation and stimulation-evoked [3H]norepinephrine overflow were compared using trains of 8, 40 or 120 monophasic pulses at 8 Hz with 1 msec duration and 40 V amplitude. Both delta selective peptides, [D-Ala2, D-Leu5]-enkephalin, met-enkephalin and leu-enkephalin, and preferential kappa ligands, dynorphin1-13 and ethylketocyclazocine, significantly reduced the vasoconstriction evoked by 8 pulses at 8 Hz. The magnitude of this effect was inversely related to the stimulus train length. In most cases, opioid agonists were highly effective with short stimulus trains, but failed to decrease vasoconstrictor responses by more than 10 to 15% with trains of 120 pulses at 8 Hz. In good correlation with these data, in tissue preincubated with [3H]norepinephrine the inhibitory effect of opioids on the tritium overflow evoked by 8 or 120 pulses at 8 Hz was inversely proportional to the length of stimulation. Our findings confirm that opioid agonists interact with a heterogeneous prejunctional receptor population to modulate the action potential-evoked release of norepinephrine in the isolated ear artery of the rabbit. This modulation is more pronounced at the beginning of a stimulus train when the negative feedback inhibition of norepinephrine release is still not fully operative. It is suggested that the physiological role of opioid peptides could be more significant during a short rather than a prolonged vasoconstriction.


Wiring Specificity and Synaptic Diversity in the Mouse Lateral Central Amygdala.
The central amygdala (CeA) nucleus, a subcortical structure composed of mostly GABA-releasing (GABAergic) neurons, controls fear expression via projections to downstream targets in the hypothalamus and brainstem. The CeA consists of the lateral (CeL) and medial (CeM) subdivisions. The CeL strongly gates information transfer to the CeM, the main output station of the amygdala, but little is known about the functional organization of local circuits in this region. Using cluster analysis, we identified two major electrophysiologically distinct CeL neuron classes in mouse amygdala slices, the early-spiking (ES) and late-spiking (LS) neurons. These two classes displayed distinct autaptic transmission. Compared with LS neurons, ES neurons had strong and depressing autapses, which enhanced spike-timing precision. With multiple patch-clamp recordings, we found that CeL neurons made chemical, but not electrical, synapses. Analysis of individual connections revealed cannabinoid type 1 receptor-mediated suppression of the ES, but not of the LS cell output synapse. More interestingly, the efficacy of the ES→LS or LS→ES synapse was ~2-fold greater than that of the LS→LS or ES→ES synapse. When tested at 20 Hz, synapses between different neurons, but not within the same class, were markedly depressing and were more powerful to sculpt activity of postsynaptic neurons. Moreover, neurons of different classes also form synapses with higher degree of connectivity. We demonstrate that ES and LS neurons represent two functionally distinct cell classes in the CeL and interactions between presynaptic and postsynaptic neurons dictate synaptic properties between neurons. The central lateral amygdala (CeL) is a key node in fear circuits, but the functional organization of local circuits in this region is largely unknown. The CeL consists of mostly GABAergic inhibitory neurons with different functional and molecular features. Here, we report that the presynaptic cell class determines functional properties of autapses and cannabinoid-mediated modulation of synaptic transmission between neurons, whereas presynaptic versus postsynaptic cell classes dictate the connectivity, efficacy, and dynamics of GABAergic synapses between any two neurons. The wiring specificity and synaptic diversity have a great impact on neuronal output in amygdala inhibitory networks. Such synaptic organizing principles advance our understanding of the significance of physiologically defined neuronal phenotypes in amygdala inhibitory networks.


Blind and fully constrained unmixing of hyperspectral images.
This paper addresses the problem of blind and fully constrained unmixing of hyperspectral images. Unmixing is performed without the use of any dictionary, and assumes that the number of constituent materials in the scene and their spectral signatures are unknown. The estimated abundances satisfy the desired sum-to-one and nonnegativity constraints. Two models with increasing complexity are developed to achieve this challenging task, depending on how noise interacts with hyperspectral data. The first one leads to a convex optimization problem and is solved with the alternating direction method of multipliers. The second one accounts for signal-dependent noise and is addressed with a reweighted least squares algorithm. Experiments on synthetic and real data demonstrate the effectiveness of our approach.


Immunological characterization of Neospora caninum cyclophilin.
Neospora caninum is an intracellular parasite that poses a unique ability to infect a variety of cell types by causing host cell migration. Although previous studies demonstrated that parasite-derived proteins could trigger host cell migration, the related molecules have yet to be determined. Our study aimed to investigate the relationship between Neospora-derived molecules and host cell migration using recombinant protein of N. caninum cyclophilin (NcCyp). Indirect fluorescent antibody test revealed that NcCyp was expressed in the tachyzoite cytosol. Furthermore, NcCyp release from extracellular parasites was detected by sandwich enzyme-linked immunosorbent assay in a time-dependent manner. Recombinant NcCyp caused the cysteine-cysteine chemokine receptor 5-dependent migration of murine and bovine cells. Furthermore, immunohistochemistry indicated that NcCyp was consistently detected in tachyzoites distributed within or around the brain lesions. In conclusion, N. caninum-derived cyclophilin appears to contribute to host cell migration, thereby maintaining parasite/host interactions.


Light-Induced Proton Release by the Cyanobacterium Anabaena variabilis: Dependence on CO(2) and Na.
Light-induced acidification by the cyanobacterium Anabaena variabilis is biphasic (a fast phase I and slow phase II) and shown to be sodium-dependent with an optimum concentration of 40 to 60 millimolar Na(+). Cells grown under low CO(2) concentrations at pH 9 (i.e. mainly HCO(3) (-) present in the medium) exhibited the slow phase II of proton efflux only, while cells grown under low CO(2) concentrations at pH 6.3 (i.e. CO(2) and HCO(3) (-) present) exhibited both phases. Light-induced proton release of phase I was dependent on inorganic carbon available in the bathing medium with an apparent K(m) for CO(2) of 20 to 70 micromolar. As was concluded from the CO(2) dependence of acidification measured at different pH of the bathing medium, bicarbonate inhibited phase-I acidification noncompetetively. Acidification was inhibited by acetazolamide, an inhibitor of carbonic anhydrase. Apparently, acidification of phase I is due to a light-dependent uptake of CO(2) being converted to HCO(3) (-) by a carbonic anhydrase-like function of the HCO(3) (-)-transport system (M Volokita, D Zenvirth, A Kaplan, L Reinhold 1984 Plant Physiol 76: 599-602) before or during entering the cell, thus releasing one proton per CO(2) converted to HCO(3) (-).


Size at Birth, Postnatal Growth, and Reproductive Timing in an Australian Microbat.
Reproductive phenology, size at birth, and postnatal growth are important life history traits that reflect parental investment. The ability to document detailed changes in these traits can be a valuable tool in the identification and management of at-risk wildlife populations. We examined reproductive traits in a common, widespread Australian microbat, Chalinolobus gouldii, at two sites over two years and derived growth curves and age estimation equations which will be useful in the study of how intrinsic and extrinsic factors alter parental investment strategies. We found that male and female offspring did not differ significantly in their size at birth or their postnatal growth rates. Bats born in 2018 were smaller at birth but grew at a faster rate than those born in 2017. When date of birth was compared across sites and years, we found bats born in 2018 had a later median birthdate (by 18 days) and births were more widespread than those born in 2017. Cooler and wetter weather during late gestation (Nov) in 2018 may have prolonged gestation and delayed births. With many bats facing threatening processes it is important to study reproductive plasticity in common and widespread "model" species, which may assist in the conservation and management of threatened microbats with similar reproductive traits.


Requirement of dendritic calcium spikes for induction of spike-timing-dependent synaptic plasticity.
Spike-timing-dependent synaptic plasticity (STDP) by definition requires the temporal association of pre- and postsynaptic action potentials (APs). Yet, in cortical pyramidal neurons pairing unitary EPSPs with single APs at low frequencies is ineffective at generating plasticity. Using recordings from synaptically coupled layer 5 pyramidal neurons, we show here that high-frequency (200 Hz) postsynaptic AP bursts, rather than single APs, are required for both long-term potentiation (LTP) induction and NMDA channel activation during EPSP-AP pairing at low frequencies. Furthermore, we find that AP bursts can lead to LTP induction and NMDA channel activation during EPSP-AP pairing at both positive and negative times. High-frequency AP bursts generated supralinear calcium signals in basal dendrites suggesting the generation of dendritic calcium spikes, as has been observed previously in apical dendrites during AP burst firing at frequencies greater than 100 Hz. Consistent with a role of these dendritic calcium spikes in LTP induction, pairing EPSPs with low frequency (50 Hz) AP bursts was ineffective in generating LTP. Furthermore, supralinear calcium signals in basal dendrites during AP bursts were blocked by low concentrations of the T- and R-type calcium channel antagonist nickel, which also blocked LTP and NMDA channel activation. These data suggest an important role of dendritic calcium spikes during AP bursts in determining both the efficacy and time window for STDP induction.


Evolution of treatment paradigms in neovascular age-related macular degeneration: a review of real-world evidence.
The aim of this work was to evaluate the contribution of real-world evidence (RWE) in changing anti-vascular endothelial growth factor (VEGF) therapy treatment practices and improving real-world treatment strategies for neovascular age-related macular degeneration (nAMD).A PubMed literature search was performed to review the large number of English-language studies conducted to investigate the real-world effectiveness of anti-VEGF (aflibercept and ranibizumab) treatment paradigms available for nAMD.The evidence for pro re nata (PRN), treat-and-extend (T&E) and fixed bimonthly dosing regimens for anti-VEGF treatment of nAMD were reviewed and findings are summarised. RWE demonstrated that T&E regimens optimise visual outcomes while reducing burden on patients, clinics and physicians, compared with both fixed-dose and PRN regimens.RWE has helped to develop and improve real-world treatment strategies in nAMD, with the aim of optimising visual outcomes and reducing treatment burden in clinical practice. Of the various regimens, a T&E regimen is most likely to adequately balance clinical outcomes and treatment burden for patients with nAMD.


Newborn Health Indicators Associated with Maternal Age during First Pregnancy.
Delaying motherhood is becoming increasingly common, raising questions of the possible influence that maternal age may have on newborn health. Therefore, the objective of this study was to determine the association between maternal age and different newborn health parameters. An observational study was conducted in Spain on primiparous women and their infants. Data were collected on newborn health variables, breastfeeding, and different clinical practices that are beneficial for child health and development. Crude and adjusted mean differences were calculated along with the standard error of the mean. A total of 373 women and their children participated. In terms of early commencement skin-to-skin contact, the mean age of women that did skin-to-skin contact was 29.95 ± 0.31 years compared to 31.49 ± 0.66 years in those that did not (p = 0.042). In terms of other newborn parameters, such as preterm birth, health problems or complications, or the need for hospital admission, these were more frequent in the oldest group of mothers, but the differences found were not significant (p > 0.05). Hence, indicators of newborn morbidity were not found to be significantly associated with maternal age; however, beneficial practices such as early commencement skin-to-skin contact were found to be significantly associated with maternal age.


Trichophyton Rubrum with the 'raubitschekii' morphotype: the first report from Turkey.
In modern taxonomy, Trichophyton rubrum with the 'raubitschekii' morphotype differs from the common strains of T. rubrum morphologically, physiologically, and clinically, despite genetic homogeneity. In this paper, we report the first autochthonous Turkish cases in a 24-year-old woman and her 26-year-old fiancé with tinea cruris and tinea manuum, respectively. The isolates were proven to be T. rubrum with the 'raubitschekii' morphotype by their morphological and physiological characteristics including the following: (1) granular colony surface, (2) profuse macroconidia and microconidia, (3) strongly positive urease activity after 3 days, (4) non-perforating hair, (5) restricted growth and producing no alkaline reaction on bromocresol purple-milk solids-glucose agar, and (6) restricted growth and producing no conidia on 3-9% NaCl-supplemented Sabouraud agar. The internal transcribed spacer (ITS) regions of both isolates were sequenced, and the assembled DNA sequences were examined using the Basic BLAST (nucleotide-nucleotide) software of the National Center for Biotechnology Information web database. Actually, the lack of epidemiological data on this variety is notable, and the actual prevalence is unknown. Otherwise, routine methods misidentified the strains as T. rubrum or unrecognized cases were underreported.


Prediction of coagulating and noncoagulating milk samples using mid-infrared spectroscopy.
Recently, a general deterioration of milk coagulation properties (MCP) has been observed in Italy; thus, the prediction of noncoagulating (NC) milk, defined as milk not forming a curd within 30min from rennet addition, is of immediate interest in the Italian cheese industry. The present study investigated the ability of mid-infrared (MIR) spectroscopy to predict NC milk using individual and bulk samples from Holstein cows. Samples were selected according to MIR analysis to cover the range of coagulation time between 5 and 60min. Milks were then analyzed for MCP through the reference instrument (Formagraph) over an extended testing period of 60min to identify coagulating and NC samples. Measured traits were rennet coagulation time, curd-firming time, and curd firmness 30 and 60min after rennet addition. Results showed no specific spectral information distinguishing NC from coagulating samples. The most accurate prediction model was developed for rennet coagulation time followed by curd-firming time and curd firmness 30min after rennet addition, whereas curd firmness 60min after enzyme addition could not be accurately predicted. Based on these findings, MIR spectroscopy might be proposed in payment systems to reward or penalize milk according to MCP. Moreover, the ability of MIR spectroscopy to predict the MCP of samples that form a curd beyond 30min from enzyme addition may be of interest for genetic improvement of coagulation traits in dairy breeds, because until now most studies have excluded NC information from genetic analysis, leading to possible biases in the estimation of genetic parameters and in the prediction of sire's merit for MCP.


Vaginal delivery following caesarean section-the use of oxytocin and prostaglandins.
Five hundred and twenty women with one previous caesarean section underwent a trial of labour in our department during the past five years. They were divided into three groups-those receiving oxytocin, those receiving prostaglandins, and those unstimulated who had spontaneous labour. The obstetric outcomes were compared. Rates of vaginal delivery in the three groups were 65%, 67% and 72%, respectively. No mother died and there were no cases of complete uterine rupture. Our results confirm similar reports that vaginal delivery after a previous caesarean section can be safely achieved in about two-thirds of patients. Serious complications are minimal when the use of oxytocin and prostaglandins is carefully monitored.


Neutrophils promote inflammatory angiogenesis via release of preformed VEGF in an in vivo corneal model.
We investigated the role of neutrophilic cells (neutrophils) in inflammatory angiogenesis and explored the possible mechanisms involved. Corneal angiogenesis was induced in vivo with a 75% silver nitrate applicator. Depletion of neutrophils was accomplished by the intraperitoneal administration of RB6-8C5, a neutrophil-depleting antibody. Angiogenesis, neutrophil infiltration, and the localization of vascular endothelial growth factor (VEGF) were evaluated by biomicroscopic observations, histology, and immunohistochemistry in control and RB6-8C5 treatment groups. Protein levels of VEGF, macrophage inflammatory protein-1alpha (MIP-1alpha), macrophage inflammatory protein-2 (MIP-2), and tumor necrosis factor alpha in the cornea were determined by enzyme-linked immunosorbent assay. An in vitro model of neutrophil activation was also used to examine the ability of neutrophils to produce and release VEGF, MIP-1alpha, and MIP-2. At day 1 after injury, neutrophil infiltration in the cornea was highest, and VEGF was expressed in the infiltrating neutrophils. The enhanced protein levels of VEGF, MIP-1alpha, and MIP-2 correlated with the degree of neutrophil infiltration. Neutrophil depletion significantly inhibited corneal angiogenesis and reduced the protein levels of VEGF, MIP-1alpha, and MIP-2 in the cornea. Upon stimulation, isolated neutrophils released VEGF from preformed stores and MIP-1alpha and MIP-2 by de novo synthesis. Neutrophil depletion thus significantly impaired inflammatory angiogenesis, identifying neutrophils as an important player in inflammatory angiogenesis. Neutrophils may exercise their angiogenic function by releasing proangiogenic factors such as VEGF. Intervention measures targeting neutrophils may therefore help to deal with abnormal angiogenesis involved in chronic inflammatory diseases.


Does school bullying affect adult health? Population survey of health-related quality of life and past victimization.
The purpose of the present study was to determine the proportion of adult South Australians who report having experienced school bullying and to examine the relationship between past victimization and adult health-related quality of life. A representative sample (n=2833) of metropolitan and country South Australian adults were asked in a face-to-face interview whether they had experienced bullying when they were at school. Health-related quality of life was measured using the Medical Outcomes Study Short Form 36-item health survey questions (SF-36). Regression analyses (linear and logistic) were performed, taking into account survey weights. Nearly one-fifth of adults reported having experienced bullying when they were at school. Older persons and those born overseas were less likely to report having been bullied. Those reporting that they had been bullied experienced significantly poorer mental and physical health compared to those who had not been bullied. Adults commonly reported experiencing bullying while at school and these reports were associated with lower health-related quality of life in adulthood. School bullying needs further investigation as a preventable cause of mental health problems across the lifespan.


Muscle temperature and EMG amplitude and frequency during isometric exercise.
While muscle temperature is known to vary with environmental temperature and the insulation provided by clothing, little has been published examining the interrelationships between the amplitude and frequency of the electromyogram (EMG), muscle tension, muscle fatigue, and muscle temperature. Seven male subjects immersed their arms and legs in water at 24, 27, 34, and 37 degrees C for 20 min. Muscle temperature, strength (maximal voluntary contraction; MVC), endurance for a fatiguing contraction at 40% MVC, and EMG were assessed in the handgrip, biceps brachii, quadriceps, and gastrocnemius muscles. MVC was 44.8% lower for all muscles examined at the coldest muscle temperature. For all temperatures, the relationship between EMG amplitude and tension for brief isometric contractions was nearly linear; however, the increase in the amplitude of the EMG with muscle fatigue was reduced for the coldest muscle temperatures. The frequency components of the EMG and motor unit conduction velocity were largely unaffected by muscle tension but were inversely related to muscle temperature, with a 10 degrees C reduction in temperature resulting in a 32 Hz reduction in the center frequency. During fatiguing contractions at a tension of 40% MVC, the percent reduction in frequency was similar for all muscle temperatures, being reduced by about 20% from the beginning to the end of the contractions. EMG amplitude can be used to assess muscle use in most physiological conditions, but the frequency components of the EMG are so related to temperature as to make its use more restricted.


Antithrombotic effects of 3-([1:1',2':1"]-3'-terphenyl)propanol in animals.
3-([1:1',2':1"]-3'-Terphenyl)propanol (CAS 186835-06-3, F050) and acetylsalicylic acid (ASA) inhibited platelet aggregation induced by CaCl2, arachidonic acid, collagen, adenosine diphosphate (ADP) and thrombin in guinea pigs, rabbits and rats in vitro. However, F050 had a wider spectrum of actions than ASA. Orally administered F050 inhibited platelet aggregation ex vivo. F050 significantly reduced the thrombus formation in the extracorporeal circulation thrombosis model in guinea pigs. It inhibited erythrocyte hemolysis induced by hypotonic NaCl, while ASA did not. F050, but not ASA, inhibited increases in platelet [CA2+]i caused by thrombin in guinea pigs. F050 is a parent compound that will facilitate the development of an orally active drug for the treatment of thrombotic diseases.


The effect of synovial catabolin on cartilage synthetic activity.
The effect of porcine synovial catabolin on the incorporation of [3H]amino acids and [35S]sulfate into bovine nasal cartilage was investigated. The rapid breakdown of matrix caused by partially purified catabolin had little affect on the incorporation of [3H]amino acids but there was inhibition of [35S]sulfate uptake. While the 35S-labelled material released into the medium was largely incapable of aggregation with hyaluronate, this was only a small part (less than 10%) of the total incorporated. The principal inhibitory action was in the formation of large molecular size material (guanidinium chloride extractable). The amount of newly synthesized glycosaminoglycans (GAG) during the 8 day culture period was too low (less than 0.8%) to influence the very rapid breakdown of the matrix under catabolin stimulation. Cartilage organ cultures recovered from inhibition of [35S]sulfate incorporation and from the catabolic stimulation after removal of catabolin. It is suggested that the two properties of the catabolin preparation demonstrated in this study may work synergistically both in causing and prolonging cartilage damage in vivo.


Statins inhibit toll-like receptor 4-mediated lipopolysaccharide signaling and cytokine expression.
Toll-like receptor 4 (TLR4) is the main receptor for Lipopolysaccharide (LPS). Two relatively common variants of the TLR4 gene are present, resulting in changes from aspartic acid (D) to glycine (G) at residue 299 and from threonine (T) to isoleucine (I) at residue 399, respectively. It has been shown that statins have a greater effect on lowering risk of cardiovascular events in individuals carrying the 299G allele than in those not carrying this allele. We investigated possible mechanisms underlying this synergy of statin treatment and TLR4 genotype. In cells expressing the 299D-399T TLR4, LPS activated the transcription factor NFkappaB and increased the expression of interleukin-6 and tumor necrosis factor-alpha, and these effects were reduced by pretreatment of the cells with pravastatin or simvastatin. LPS-induced NFkappaB activation and interleukin-6 and tumor necrosis factor-alpha expression were substantially reduced in cell expressing the 299G-399T or 299D-399I variant, and undetectable in cells expressing the 299G-399I TLR4. The 3-hydroxy-3-methylglutaryl coenzyme A pathway inhibitors, Y27632 and GGTI-286, exhibited a similar effect to statins, suggesting that the inhibitory effect of statins was mediated by the 3-hydroxy-3-methylglutaryl coenzyme A pathway. The results of this study indicate that the TLR4 variations and statins have an additive inhibitory effect on TLR4-mediated inflammatory response, providing a potential explanation for the finding that the beneficial effect of statins on cardiovascular risk is dependent on TLR4 genotype.


[Analysis of time-frequency characteristics and coherence of local field potentials during working memory task of rats after high-frequency repeated transcranial magnetic stimulation].
Repetitive transcranial magnetic stimulation(rTMS) is a painless and non-invasive method for stimulation and modulation in the field of cognitive neuroscience research and clinical neurological regulation. In this paper, adult Wistar rats were divided into the rTMS group and control group randomly. Rats in the rTMS group were stimulated with 5 Hz rTMS for 14 days, while the rats in the control group did not accept any stimulation. Then, the behavior and local field potentials (LFPs) were recorded synchronously when the rats perform a working memory (WM) task with T-maze. Finally, the time-frequency distribution and coherence characteristics of the LFPs signal in the prefrontal cortex (PFC) during working memory task were analyzed. The results showed that the rats in the rTMS group needed less training days to reach the task correction criterion than the control group (P < 0.05). Compared with the control group, the rTMS group has higher energy (P < 0.01) in θ band (4~12 Hz) and γ band (30~80 Hz). The coherence between the channel pairs decreases as the spatial distance of the channel pairs increases, and the rTMS group exhibits a higher coherence than the control group (P < 0.01). It is concluded that 5 Hz rTMS can improve the excitability of rat prefrontal cortical neurons to a certain extent, and has a positive effect on the working memory ability of normal rats. The results of this paper may provide important theoretical support for further research on the mechanism of action of rTMS on WM.


Toward total automation of microfluidics for extraterrestial in situ analysis.
Despite multiple orbiter and landed missions to extraterrestrial bodies in the solar system, including Mars and Titan, we still know relatively little about the detailed chemical composition and quantity of organics and biomolecules in those bodies. For chemical analysis on astrobiologically relevant targets such as Mars, Europa, Titan, and Enceladus, instrumentation should be extremely sensitive and capable of analyzing a broad range of organic molecules. Microchip capillary electrophoresis (μCE) with laser-induced fluorescence (LIF) detection provides this required sensitivity and targets a wide range of relevant markers but, to date, has lacked the necessary degree of automation for spaceflight applications. Here we describe a fully integrated microfluidic device capable of performing automated end-to-end analyses of amino acids by μCE with LIF detection. The device integrates an array of pneumatically actuated valves and pumps for autonomous fluidic routing with an electrophoretic channel. Operation of the device, including manipulation of liquids for sample pretreatment and electrophoretic analysis, was performed exclusively via computer control. The device was validated by mixing of laboratory standards and labeling of amino acids with Pacific Blue succinimidyl ester followed by electrophoretic analysis. To our knowledge, this is the first demonstration of completely automated end-to-end μCE analyses on a single, fully integrated microfluidic device.