[Double-blind therapeutic trial of spironolactone in arterial hypertension].
Spironolactone is a diuretic, selective aldosterone, antagonist with its own antihypertensive action which prevents body loss of potassium. Its clinical use has been documented on the treatment of essential arterial hypertension; however, there does not seem to be enough information to form a solid chemical criterion. This work is a clinical evaluation of the antihypertensive effect of the drug using double-blind technic with 41 patients with essential arterial hypertension, all external patients from the Instituto de Cardiología. They were divided in two groups, selected at random, to be able to observe their tensional range with spironolactone every two weeks, during 16 weeks; and using a placebo for the next 16 weeks. On group following this order; and the other one viceversa. After 32 weeks, the results observed show the effect of placebo, as well as spironolactone on arterial pressure and the statistic comparison, states the real antihypertensive effect of the drug on this group of patients. Every day doses were from 300 to 450 mg., and with it there was a rise in seric potassium of an average of 1 mEq/l. The authors suggest that this drug is useful in cases of essential hypertension although its pathway isn't deeply known. Apparently, the antihypertensive effect of spironolactone is not solely on patients with hypertension due to primary aldosteronism. The intervention on various hipertensinogenous factors in relation to its effect are discussed.


Natriuretic peptide system gene expression in human coronary arteries.
The natriuretic peptides (NPs) ANF, BNP, and CNP have potent anti-proliferative and anti-migratory effects on vascular smooth muscle cells (SMCs). These properties make NPs relevant to the study of human coronary atherosclerosis because vascular cell proliferation and migration are central to the pathophysiology of atherosclerosis. However, the existence and cytological distribution of NPs and their receptors in human coronary arteries remain undetermined. This has hampered the development of hypotheses regarding the possible role of NPs in human coronary disease. We determined the pattern of expression of NPs and their receptors (NPRs) in human coronary arteries with atherosclerotic lesions classified by standard histopathological criteria as fatty streak/early atherosclerotic lesions, intermediate plaques, or advanced lesions. The investigation was carried out using a combination of immunocytochemistry (ICC), in situ hybridization (ISH), and semi-quantitative polymerase chain reaction (PCR). Both by ICC and ISH, ANF was found in the intimal and medial layers of all lesions. BNP was highly expressed in advanced lesions where it was particularly evident by a strong ISH signal but weak ICC staining. CNP was demonstrable in all types of lesions, giving a strong signal by ISH and ICC. This peptide was particularly demonstrable in the endothelium, as well as in the SMCs of the intima, media, and vasa vasorum of the adventitia and in macrophages. By ISH, NPR-A was not detectable in any of the lesions but both NPR-B and NPR-C were found in the intimal and the inner medial layers. By RT-PCR, mRNA levels of all NPs tended to be increased in macroscopically diseased arteries, but only the values for BNP were significantly so. No significant changes in NPR mRNA levels were detected by PCR. In general, the signal intensity given by the NPs and their receptors by ICC or ISH appeared dependent on the type of lesion, being strongest in intermediate plaques and decreasing with increasing severity of the lesion. This study constitutes the first demonstration of NPs and NPR mRNAs in human coronary arteries and supports the existence of an autocrine/paracrine NP system that is actively modulated during the progression of atherosclerotic coronary disease. This suggests that the coronary NP system is involved in the pathobiology of intimal plaque formation in humans and may be involved in vascular remodeling.


Lung fibrosis: drug screening and disease biomarker identification with a lung slice culture model and subtracted cDNA Library.
Pulmonary fibrosis is a progressive and irreversible disorder with no appropriate cure. A practical and effective experimental model that recapitulates the disease will greatly benefit the research community and, ultimately, patients. In this study, we tested the lung slice culture (LSC) system for its potential use in drug screening and disease biomarker identification. Fibrosis was induced by treating rat lung slices with 1ng/ml TGF-β1 and 2.5μM CdCl2, quantified by measuring the content of hydroxyproline, and confirmed by detecting the expression of collagen type III alpha 1 (Col3α1) and connective tissue growth factor (CTGF) genes. The anti-fibrotic effects of pirfenidone, spironolactone and eplerenone were assessed by their capability to reduce hydroxyproline content. A subtractive hybridisation technique was used to create two cDNA libraries (subtracted and unsubtracted) from lung slices. The housekeeping gene glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was employed to assess the subtraction efficiency of the subtracted cDNA library. Clones from the two libraries were sequenced and the genes were identified by performing a BLAST search on the NCBI GenBank database. Furthermore, the relevance of the genes to fibrosis formation was verified. The results presented here show that fibrosis was effectively induced in cultured lung slices, which exhibited significantly elevated levels of hydroxyproline and Col3α1/CTGF gene expression. Several inhibitors have demonstrated their anti-fibrotic effects by significantly reducing hydroxyproline content. The subtracted cDNA library, which was enriched for differentially expressed genes, was used to successfully identify genes associated with fibrosis. Collectively, the results indicate that our LSC system is an effective model for the screening of drug candidates and for disease biomarker identification.


Structural and Functional Highlights of Vacuolar Soluble Protein 1 from Pathogen Trypanosoma brucei brucei.
Trypanosoma brucei (T. brucei) is responsible for the fatal human disease called African trypanosomiasis, or sleeping sickness. The causative parasite, Trypanosoma, encodes soluble versions of inorganic pyrophosphatases (PPase), also called vacuolar soluble proteins (VSPs), which are localized to its acidocalcisomes. The latter are acidic membrane-enclosed organelles rich in polyphosphate chains and divalent cations whose significance in these parasites remains unclear. We here report the crystal structure of T. brucei brucei acidocalcisomal PPases in a ternary complex with Mg(2+) and imidodiphosphate. The crystal structure reveals a novel structural architecture distinct from known class I PPases in its tetrameric oligomeric state in which a fused EF hand domain arranges around the catalytic PPase domain. This unprecedented assembly evident from TbbVSP1 crystal structure is further confirmed by SAXS and TEM data. SAXS data suggest structural flexibility in EF hand domains indicative of conformational plasticity within TbbVSP1.


Establishment and application of an index system for prevention of coal workers' pneumoconiosis: a Delphi and analytic hierarchy process study in four state-owned coal enterprises of China.
To explore the difference of cumulative incidence rate of coal workers' pneumoconiosis (CWP) among four large state-owned coal enterprises in northern China, we created an index system for evaluating the quality of comprehensive measures against CWP and applied the system to evaluate and compare the measures of the four coal enterprises. A two-round Delphi investigation was conducted to identify the indicators in the index system. The weight values of the indicators were calculated with analytic hierarchy process methods. Measures of CWP, mine annals, records and other information in each coal mine of the four enterprises were collected. The evaluation scores, which ranged from 0 to 100, were calculated and compared with. A three-grade index system with 3 first-grade indicators, 9 second-grade indicators and 44 tertiary-grade indicators was established. The expert authority coefficient (Cr ) was 0.75 and the Kendall's coefficient of concordance (Kendall's W) was 0.15 (χ2=193.30, P<0.001). The weight value of 'Geological conditions' was 0.43, equal to 'Dust control engineering technology', and that of 'Occupational health management' was 0.14. The medians and quartiles of the evaluation scores of comprehensive measures against CWP of the four enterprises were 58.38 (54.60~63.02), 64.63 (60.83~67.06), 72.99 (68.92~77.67) and 75.07 (70.73~79.20), respectively. The index system could be effectively used for evaluation and comparison of the comprehensive measures against CWP among different enterprises. The geological conditions and dust control engineering technology played an important role in preventing and controlling CWP.


Beat (Beat Eating Disorders).
This charity website provides a comprehensive range of information on eating disorders. There is an overview section about different types of eating disorders, which is in clear and easily understood terms, giving readers the option to seek more detailed information.


Differential effects of high dietary levels of vitamin A on the vitamin E-selenium nutrition of young and adult chickens.
Experiments were conducted to determine the nature of the interaction of high levels of vitamin A and vitamin E-selenium nutrition in the chicken. Results showed that chicks were protected from the vitamin E-selenium deficiency disease exudative diathesis (ED) by a high dietary level of vitamin A (1.0 X 10(6) IU/kg) which moderately depressed growth. A greater concentration (1.5 X 10(6) IU/kg) of vitamin A in the diets of hens fed a low vitamin E diet hastened their depletion of plasma tocopherols and increased plasma glutathione peroxidase (GSH-px) activity. At hatching the progeny of vitamin A-fed hens were severely depleted of plasma tocopherols but had normal plasma GSH-px activities. They showed increased susceptibility to ED when fed selenium-deficient, vitamin E-free diets for 2 weeks. Absorption studies using ligated duodenal loops or oral doses indicated that high-level dietary vitamin A promoted the enteric absorption of selenium but interfered with the absorption of vitamin E. The dual nature of these effects was related to the ED-protective influence of vitamin A when fed to chicks, and the ED-stimulative influence on progeny when vitamin A was fed to dams.


Inpatient hospital admission rates for nonmalignant respiratory disease among workers exposed to metal removal fluids at a U.S. automobile manufacturer.
This study was undertaken to determine the impact of exposure to metal removal fluids (MRFs) on the respiratory health of exposed workers. The outcome measure selected was the rate of hospital admissions for nonmalignant respiratory disease episodes as determined from healthcare insurance claims data. A cohort of MRF-exposed employees was assembled from 11 manufacturing facilities where MRFs were extensively used in the manufacture of automotive engines, transmissions, and other machined parts. The MRF-exposed cohort included 20,434 employees of such facilities who worked at any time from 1993 through 1997. A non-MRF-exposed cohort was assembled from other employees of the same company during the same time period, but working in warehouse operations and other manufacturing facilities that did not use MRFs or any known respiratory sensitizing agents. The non-exposed cohort included 8681 employees. The crude hospital admission rate for the MRF-exposed cohort was 44 percent higher than that of the non-exposed cohort over the 5-year study period (6.67 vs. 4.62 per 1000 person years at risk, p < 0.05). With age adjustment, the MRF population's rate was still 35 percent higher, and still statistically significant. A nested case-control study was also conducted to determine whether the risk of hospital admission increased with the level of MRF exposure in the population working in MRF plants. The industrial hygiene reconstruction found the levels of exposures of both cases and controls to be very low, with the vast majority of study subjects (more than 90%) having exposures of less than 0.5 mg/m(3). The case-control study did not find any association between increased levels of MRF exposure and risk of hospitalization. The study did document an elevated risk of hospitalization among a sizable population employed in manufacturing operations where MRFs are used.


[Epidemiological investigation of allergic rhinitis in Ningxia].
Objective: To investigate the epidemiological characteristics of allergic rhinitis (AR) in Ningxia and to analyze its related factors. Methods: From March to September of 2013, a multi-stage and cluster sampling method was used to investigate the diagnosis and treatment of AR in Ningxia Area (3 years and above). Guidelines for diagnosis and treatment of allergic rhinitis (2009, Wuyishan) was used as the basis for the diagnosis of adult AR, while Guidelines for diagnosis and treatment of pediatric allergic rhinitis (2010, Chongqing) was used as the basis for children. SPSS 16.0 software was used to complete the statistical analysis. Results: The total number of questionnaires was 6 000, and the number of effective questionnaire was 5 236, the recovery rate was 87.27%. With 684 cases diagnosed of AR, the prevalence of AR in Ningxia was 13.06% (684/5 236), including 13.40% (325/2 425) of males, 12.77% (359/2 811) of females. The difference was not statistically significant (χ(2)=0.456, P>0.05). There was significant difference in the prevalence between Hui and Han [14.35% (452/3 150) vs 11.12% (232/2 086), χ(2)=11.51, P<0.05]. According to ARIA criteria, persistent AR was 27.63% (189/684), intermittent AR was 72.37% (495/684). The month with highest incidence of AR in Ningxia Area was September, accounting for 71.78% (491/684). The prevalence of urban population was 14.54%, with the prevalence of rural population was 11.90%, and the difference was significant between urban and rural residents (χ(2)=7.90, P<0.05). The age group with highest prevalence rate was 21~30 years old. The main inhalation allergens were mugwort (68.42%), weeds (58.48%) and ragweed (55.56%). The main dietary allergens were wheat flour (14.33%), peanut (13.74%) and walnut kernel (11.99%). The most common complication was allergic conjunctivitis [82.02% (561/684)]. Conclusion: The epidemiology of AR in Ningxia Area is preliminarily understood, which will provide the epidemiological evidence for the prevention and treatment of AR and the formulation of public health policy.


[Estimation of Probiotic Lactobacilli Drug Resistance].
An actual problem of analysis of probiotic lactobacilli resistance to antibiotics and other drugs used in the treatment of gastro-intestinal disturbances has been for the first time solved. The levels of resistance of 19 strains of Lactobacillus (14 strains of L. fermentum, 4 strains of L.plantarum and 1 strain of L.rhamnosus) isolated from commercial probiotics and sour milk products to 14 antibiotics of various nature, i.e. β-lactams, aminoglycosides, macrolides, clindamycin, vancomycin, rifampicin, ciprofloxacin, tetracycline and chloramphenicol were determined. All the isolates were practically susceptible to the drugs of the first line antihelicobacterial therapy, i.e. amoxicillin and clarithromycin, that makes inexpedient the parallel use of the probiotics containing the above lactobacilli in the treatment of gastritis and gastric ulcer, despite the lactobacilli antagonism with respect to Helicobacter pylory. Lactobacilli are as well resistant to mesalazin and can be used for correction of dysbiosis in inflammatory affections of the intestine.


Six-rowed spike4 (Vrs4) controls spikelet determinacy and row-type in barley.
Inflorescence architecture of barley (Hordeum vulgare L.) is common among the Triticeae species, which bear one to three single-flowered spikelets at each rachis internode. Triple spikelet meristem is one of the unique features of barley spikes, in which three spikelets (one central and two lateral spikelets) are produced at each rachis internode. Fertility of the lateral spikelets at triple spikelet meristem gives row-type identity to barley spikes. Six-rowed spikes show fertile lateral spikelets and produce increased grain yield per spike, compared with two-rowed spikes with sterile lateral spikelets. Thus, far, two loci governing the row-type phenotype were isolated in barley that include Six-rowed spike1 (Vrs1) and Intermedium-C. In the present study, we isolated Six-rowed spike4 (Vrs4), a barley ortholog of the maize (Zea mays L.) inflorescence architecture gene RAMOSA2 (RA2). Eighteen coding mutations in barley RA2 (HvRA2) were specifically associated with lateral spikelet fertility and loss of spikelet determinacy. Expression analyses through mRNA in situ hybridization and microarray showed that Vrs4 (HvRA2) controls the row-type pathway through Vrs1 (HvHox1), a negative regulator of lateral spikelet fertility in barley. Moreover, Vrs4 may also regulate transcripts of barley SISTER OF RAMOSA3 (HvSRA), a putative trehalose-6-phosphate phosphatase involved in trehalose-6-phosphate homeostasis implicated to control spikelet determinacy. Our expression data illustrated that, although RA2 is conserved among different grass species, its down-stream target genes appear to be modified in barley and possibly other species of tribe Triticeae.


[Comparison of SPECT images with four kinds of 99mTc collimators].
Performance of SPECT imaging systems which use a rotating gamma camera, are affected by characteristics of the detector-collimator assembly, the data acquisition method, and the filter used in image reconstruction. The purpose of this study is to examine image qualities of SPECT with different types of low energy collimators. The SPECT imaging system in this study is a rotating gamma camera ZLC-7500 (Siemens) and a data processing unit Scintipac-700 (Shimadzu). The four types of collimators compared are UHR (ultra high resolution), HR (high resolution), AP (general all purpose), and HS (high sensitivity), with 0.27, 0.66, 1.00, and 2.06 relative sensitivity, respectively. In the case of the same collimator, the spatial resolutions measured in the slice plane showed a slight difference in the FWHM values (mean values of UHR, HR, AP, and HS were 11.3 mm, 13.6 mm, 15.8 mm, and 20.4 mm, respectively.) between the center and the circumference of the field of view, in the radial direction, but a large difference in the tangential direction, with lower FWHM values (values of UHR, HR, AP, and HS were 8.4 mm, 8.7 mm, 9.3 mm, and 10.8 mm at 12 cm from the center, respectively.). In comparison of SPECT images with the four types of collimators, except for the HS collimator, image qualities of UHR, HR, and AP collimators showed only a slight difference. From the pont of view of sensitivity and spatial resolution of the collimator, it is expected that the AP collimator would be suitable for SPeCT imaging with 99mTc.


Conjunctival necrosis due to subconjunctival injection of betamethasone in treatment of graft rejection after penetrating keratoplasty.
A rare side effect of betamethasone applied subconjunctivally is described. A 51-year-old man who had undergone penetrating keratoplasty in his left eye 2 months previously developed graft rejection and was treated by subconjunctival injection of betamethasone. Within 2 weeks, the patient complained of conjunctival hyperemia and irritation. Biomicroscopic examination revealed conjunctival and subconjunctival necrosis with white necrotic tissue at the subconjunctival corticosteroid injection site. Simple debridement and primary wound closure of the involved area resulted in complete healing. Ophthalmologists should be aware that subconjunctival injection of betamethasone may cause conjunctival necrosis.


Characterization of the complete chloroplast genome of Carex myosuroides Villars, 1779 (Cyperaceae).
Carex myosuroides Villars, 1779 is a typical alpine sedge with both ecological and agricultural value. The work reported here is the first complete chloroplast genome of this species. The chloroplast genome, with a total size of 185,609 bp, consists of two inverted repeats (IRs, 38,374 bp) separated by a large single-copy (LSC, 99,911 bp) region, and a small single-copy (SSC, 8950 bp) region. The overall genome GC content is 34.12%. The genome contains 125 genes, consisting of 82 protein-coding genes, 35 tRNA genes, and eight rRNA genes. Phylogenetic analysis supports the taxonomic treatment of incorporating genus Kobresia to a broader circumscription of Carex. Our work could be helpful to future research on Cyperaceae.


Calcium Pumps and Interacting BON1 Protein Modulate Calcium Signature, Stomatal Closure, and Plant Immunity.
Calcium signaling is essential for environmental responses including immune responses. Here, we provide evidence that the evolutionarily conserved protein BONZAI1 (BON1) functions together with autoinhibited calcium ATPase10 (ACA10) and ACA8 to regulate calcium signals in Arabidopsis. BON1 is a plasma membrane localized protein that negatively regulates the expression of immune receptor genes and positively regulates stomatal closure. We found that BON1 interacts with the autoinhibitory domains of ACA10 and ACA8, and the aca10 loss-of-function (LOF) mutants have an autoimmune phenotype similar to that of the bon1 LOF mutants. Genetic evidences indicate that BON1 positively regulates the activities of ACA10 and ACA8. Consistent with this idea, the steady level of calcium concentration is increased in both aca10 and bon1 mutants. Most strikingly, cytosolic calcium oscillation imposed by external calcium treatment was altered in aca10, aca8, and bon1 mutants in guard cells. In addition, calcium- and pathogen-induced stomatal closure was compromised in the aca10 and bon1 mutants. Taken together, this study indicates that ACA10/8 and BON1 physically interact on plasma membrane and function in the generation of cytosol calcium signatures that are critical for stomatal movement and impact plant immunity.


SOD2 rs4880 and GPX1 rs1050450 polymorphisms do not confer risk of COVID-19, but influence inflammation or coagulation parameters in Serbian cohort.
Objectives: Due to the role of oxidative stress in the pathophysiology of COVID-19, it is biologically plausible that inter-individual differences in patients' clinical manifestations might be affected by antioxidant genetic profile. The aim of our study was to assess the distribution of antioxidant genetic polymorphisms Nrf2 rs6721961, SOD2 rs4880, GPX1 rs1050450, GPX3 rs8177412, and GSTP1 (rs1695 and rs1138272) haplotype in COVID-19 patients and controls, with special emphasis on their association with laboratory biochemical parameters.Methods: The antioxidant genetic polymorphisms were assessed by appropriate PCR methods in 229 COVID-19 patients and 229 matched healthy individuals.Results: Among examined polymorphisms, only GSTP1 haplotype was associated with COVID-19 risk (p = 0.009). Polymorphisms of SOD2 and GPX1 influenced COVID-19 patients' laboratory biochemical profile: SOD2*Val allele was associated with increased levels of fibrinogen (p = 0.040) and ferritin (p = 0.033), whereas GPX1*Leu allele was associated with D-dimmer (p = 0.009).Discussion: Our findings regarding the influence of SOD2 and GPX1 polymorphisms on inflammation and coagulation parameters might be of clinical importance. If confirmed in larger cohorts, these developments could provide a more personalized approach for better recognition of patients prone to thrombosis and those for the need of targeted antiox-idant therapy.


Twelve possible strategies for enhancing interprofessional socialisation in higher education: Findings from an interpretive phenomenological study.
The aim of this study was to investigate the interprofessional socialisation experiences of health professional educators (HPEs) across five health science faculties in Perth, Australia. Evidence supported the importance of educators teaching and learning together, although there was minimal evidence with regard to the type of support HPEs received or required in order to socialise interprofessionally within higher education. Interview participants comprised 26 HPEs from various health-related professions across Western Australia. An interpretive phenomenological framework was used to discover the phenomena of interprofessional socialisation. The examination of the data was undertaken via qualitative content analysis with the aid of NVivo 10 software. Content coding led to the development of categories, sub-categories, and then themes. Five themes were identified; however, only one of these themes, "interprofessional socialisation strategies within higher education," is explored within this article. Based on the data within this theme, 12 possible socialisation strategies (formal and informal) were identified for HPEs, which could be implemented within health science faculties, taking into account the organisation's culture and strategic intent towards interprofessional collaboration and education.


[Safety and efficacy of DCV-based DAAs therapy for chronic HCV infection in China].
Objective: To evaluate the efficacy and safety of DCV-based DAAs therapy for chronic HCV infected Chinese patients. Methods: An open-label, non-randomized, prospective study was designed. Fifty-two patients with chronic HCV infection were enrolled. Among them, there was one patient after liver transplantation, 2 patients after kidney transplantation, 3 patients with hepatocellular carcinoma, and 4 patients with HBV infection. Thirteen cases with chronic hepatitis C (one compensated cirrhosis) who were negative for resistance-related variants [NS5A RAS (-)] of gene 1b and NS5A were treated with daclatasvir (DCV) + asunaprevir (ASV) for 24 weeks. Twenty-five cases of CHC (six compensated cirrhosis) with GT 1b, 2a, 3a, 3b, 6a were treated with DCV + SOF ± RBV for 24 weeks. 8 cases with decompensated cirrhosis of gene 1b and NS5A RAS(-) were given DCV + SOF + RBV regimen for 12 weeks. Six cases with decompensated cirrhosis, of gene 2a, 1b, 2a, 3a, 3b, were given DCV + SOF + RBV regimen for 24 weeks. HCV RNA, blood routine test, liver and kidney function, and upper abdominal ultrasound/MRI were measured at baseline, 4 weeks of treatment, end of treatment, and 12 weeks of follow-up. The incidence of adverse events and laboratory abnormalities during treatment were recorded. A t-test was used to compare the measurement data between two groups, and analysis of variance was used to compare the measurement data between multiple groups. Results: Sixteen patients (100%) achieved SVR12 after treatment, with 0% recurrence rate. Rapid virological response (RVR) of the four treatment regimens were 76.92%, 54.17%, 87.50%, and 83.33%, respectively, and 32 patients achieved 100% virological response after the completion of treatment. The incidence of adverse events of chronic hepatitis C with cirrhosis and decompensated cirrhosis was 62.5% and 64.29%, respectively. The most common adverse event was fatigue in CHC (25.00%), and elevated indirect bilirubin in decompensated cirrhosis (42.86%). No serious adverse drug events, deaths or adverse reactions occurred. Conclusion: DCV-based DAAs regimen is promising option for the treatment of HCV genotypes, compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma, and HCV infection after liver/kidney transplantation in china. Above all, it has high SVR12 with good tolerability and safety profile.


Lanthanide complexes of new nonadentate imino-phosphonate ligands derived from 1,4,7-triazacyclononane: synthesis, structural characterisation and NMR studies.
The polyamino ligand 1,4,7-tris(2-aminoethyl)-1,4,7-triazacyclononane (1) has been used to synthesise two new ligands by Schiff-base condensation with methyl sodium acetyl phosphonate to give ligand L and methyl sodium 4-methoxybenzoyl phosphonate to give ligand L1 in the presence of lanthanide ion as templating agent to form the complexes [Ln(L)] and [Ln(L1)](Ln = Y, La, Gd, Yb). Both ligands L and L1 have nine donor atoms comprising three amine and three imine N-donors and three phosphonate O-donors and form Ln(III) complexes in which the three pendant arms of the ligands wrap around the nine-coordinate Ln(III) centres. Complexes with Y(III), La(III), Gd(III) and Yb(III) have been synthesised and the complexes [Y(L)], [Gd(L)] and [Gd(L1)] have been structurally characterised. In all the complexes the coordination polyhedron about the lanthanide centre is slightly distorted tricapped trigonal prismatic with the two triangular faces of the prism formed by the macrocyclic N-donors and the phosphonate O-donors. Interestingly, given the three chiral phosphorus centres present in [Ln(L)] and [Ln(L1)] complexes, the three crystal structures reported show the presence of only one diastereomer of the four possible. 1H, 13C and 31P NMR spectroscopic studies on diamagnetic [Y(L)] and [La(L)] and on paramagnetic [Yb(L)] complexes indicate the presence in solution of all the four different diastereomers in varying proportions. The stability of complexes [Y(L)] and [Y(L1)] in D2O in both neutral and acidic media, and the relaxivity of the Gd(III) complexes, have also been investigated.


SGLT2i alleviates epicardial adipose tissue inflammation by modulating ketone body-glyceraldehyde-3-phosphate dehydrogenase malonylation pathway.
Inflammation in the epicardial adipose tissue (EAT) is a contributor to atrial fibrillation. Studies have reported that sodium glucose co-transporter 2 inhibitor (SGLT2i) can alleviate EAT inflammation. However, the mechanism remains elusive. This study aims to investigate the molecular mechanism of SGLT2i in reducing EAT inflammation and to explore the effects of SGLT2i on atrial fibrosis in atrial fibrillation. Sprague-Dawley rats were injected with angiotensin II to induce atrial fibrillation and randomly assigned to receive SGLT2i ( n = 6) or vehicle ( n = 6). Macrophages (RAW264.7) were treated with ketone bodies; ACC1 knockdown/overexpression and malonyl-CoA overexpression were performed in vitro . The levels of inflammatory cytokines, ACC1, and malonyl-CoA were examined by ELISA. GAPDH malonylation was measured by co-immunoprecipitation. In atrial fibrillation rats, SGLT2i increased the ketone body levels and decreased the expression of ACC1 and alleviated EAT inflammation and atrial fibrosis. In RAW264.7 cells, ketone bodies decreased the levels of ACC1, malonyl-CoA, and GAPDH malonylation, accompanied by reduced inflammatory cytokines. ACC1 knockdown decreased the expression of malonyl-CoA and GAPDH malonylation and alleviated lipopolysaccharide (LPS)-induced macrophage inflammation; these effects were inhibited by malonyl-CoA overexpression. Furthermore, the protective effects of ketone bodies on macrophage inflammation were abrogated by ACC1 overexpression. SGLT2i alleviates EAT inflammation by reducing GAPDH malonylation via downregulating the expression of ACC1 through increasing ketone bodies, thus attenuating atrial fibrosis.


Additive effects of ciprofloxacin on the in-vitro activity of chloroquine against a clinical isolate of Plasmodium falciparum.
As chloroquine and ciprofloxacin each possess substantial inhibitory activity against the schizonts of Plasmodium falciparum, it seems possible that a combination of the two drugs may be clinically useful. The effects on the erythrocytic stages of P. falciparum of combined treatment with chloroquine and ciprofloxacin were therefore evaluated in vitro, using the World Health Organization's standardized micro test. When used alone, the median inhibitory concentration (IC(50)) of chloroquine against the schizonts in the assay mixtures was found to be 7.75 microg/ml, whereas the corresponding value for ciprofloxacin was markedly lower, at 3.35 microg/ml. When they were used together, however, there was marked and statistically significant mutual enhancement of schizont inhibition by the two drugs, indicating that a chloroquine-ciprofloxacin combination may be useful clinically, in the treatment and management of P. falciparum malaria.


Splenic norepinephrine is decreased in MRL-lpr/lpr mice.
The MRL-lpr/lpr mouse, a genetic model of the human autoimmune disease systemic lupus erythematosus, has been studied extensively to determine the etiology and the pathological course of the disease in lymphoid organs. At approximately 8 weeks of age, splenomegaly develops due to a massive increase in an abnormal population of T cells, resulting in a disruption of the normal splenic architecture. Part of the normal splenic architecture includes postganglionic noradrenergic sympathetic nerve fibers, which can exert influence on a variety of immunological functions. Noradrenergic innervation and norepinephrine content of spleens from both male and female MRL-lpr/lpr mice and MRL(-)+/+ congenic controls were examined at 6, 12, 18, and 24 weeks of age. Norepinephrine content is reduced in MRL-lpr/lpr male and female mice prior to the onset of observed splenomegaly and remains reduced at all ages examined. Remaining noradrenergic fibers are found in their usual compartments, but are greatly diminished compared with controls.


Sexual risk behaviour among undergraduate students in Enugu, Nigeria.
This study aims to identify high-risk sexual behaviour among undergraduate students in a developing country and to formulate programmes targeted at reduction of complications of such risky sexual behaviour. This was a questionnaire survey taken of undergraduate students in four institutions of higher learning in Enugu, Nigeria over a 1-month period. The prevalence of sexual activity was 76.8%, with 85.4% of females and 62.3% of males having more than one sexual partner. More female students than their male counterparts (65.7% vs 42.2%) had their first sexual encounter as an adolescent. Sexual risk behaviour that includes having multiple sexual partners, not using a condom, anal and oral sex were more common among the lower social class, adolescents, females and those living off-campus. While economic reasons are a major factor that encourages risky sexual behaviour in the female, the urge to have sex and curiosity, tended to favour such sexual experimentation in the male. Despite a good knowledge of the complications that could follow such risky sex behaviour, the sex lives of the students remained unchanged. Educational and risk reduction programmes targeting a change in belief and behaviour is required to maintain sexual safety among these youth.


[Agitation in prehospital setting: view of emergency physicians].
Agitation is a behavioral emergency that can have numerous underlying causes, organic as well as psychiatric. The presence of a clinician and well-trained staff determine the quality of care, thus facilitating the dialog with the patient and, if needed, ensuring the safe application of medication and physical restraint. Outside the hospital, an emergency physician is best suited to manage such situations in collaboration with paramedics and police. "De-escalation" without medication or physical restraint should be the preferred end-point of an intervention in agitation. When necessary, medication and restraint should be applied, in order to enable medical evaluation of a patient. Calming without sedation seems the most advised endpoint of intervention, according to expert-opinion.


Alterations in the chemical composition and antigenicity of Escherichia coli O89 lipopolysaccharide and lipid A after 60Co gamma irradiation.
The chemical composition and the antigenicity of Escherichia coli lipopolysaccharide (LPS) and lipid A were investigated after irradiation with 150 kGy 60Co-gamma ray. Compared to the original preparations, the irradiated LPS showed a significant reduction in glucosamine, glucose and galactose and a decrease in the phosphate content. The fatty acid components were reduced to a smaller degree. Irradiation induced a reduction in the antigenicity of the polysaccharide part. The amount of glucosamine and phosphate decreased in the irradiated lipid A. The fatty acid content was significantly reduced. The alteration in the chemical composition was not paralleled by changes in the antigenicity of irradiated lipid A.


Evaluating indices of body condition in two cricket species.
Body mass components (dry mass, lean dry mass, water mass, fat mass) in each sex correlate strongly with body mass and pronotum length in Gryllus texensis and Acheta domesticus. Ordinary least squares (OLS) regression underestimates the scaling relationship between body mass and structural size (i.e., pronotum length) in both cricket species compared with standard major axis (SMA) regression. Standardized mass components correlate more strongly with scaled mass index ([Formula: see text]) than with residual body mass (R i). R i represents the residuals from an OLS regression of log body mass against log pronotum length. Neither condition index predicts energy stores (i.e., fat content) in G. texensis. R i is not correlated with energy stores in A. domesticus whereas [Formula: see text] is negatively correlated. A comparison of condition index methods using published data showed that neither sex nor diet quality affected body condition at adulthood in G. texensis when using the scaled mass index. However, the residual index suggested that sex had a significant effect on body condition. Further, analysis of covariance (ANCOVA) suggested that diet quality significantly affects body mass while statistically controlling for body size (i.e., body condition). We conclude that the statistical assumptions of condition index methods must be met prior to use and urge caution when using methods that are based on least squares in the y -plane (i.e., residual index ANCOVA).


A multicentre assessment of the endogenous thrombin potential using a continuous monitoring amidolytic technique.
This study assessed the inter-laboratory imprecision associated with the measurement of the endogenous thrombin potential (ETP). The initial studies used techniques that had evolved in each of the participating laboratories. Samples from normal healthy subjects (n = 10), two patients receiving coumarin therapy [International Normalized Ratio approximately 2.0 and approximately 4.0] and a further two subjects receiving treatment with unfractionated heparin (anti-Xa 0.07 i.u./ml and 0.31 i.u./ml) were assayed relative to a lyophilized normal plasma that had arbitrarily been assigned a potency of 100%. Considerable variation in potency estimates was observed between the centres, although individual laboratories using fully automated techniques achieved acceptable levels of imprecision as assessed by the coefficient of variation (CV) (intra-assay CV < 9.5%, inter-assay CV < 12.5%). A second study to assess a similar range of samples, using a standardized assay protocol and incorporating appraisal of two chromogenic substrates, CBS.0068 or Pefachrom TG, demonstrated markedly improved agreement in potency estimates between centres and good correlation (r > 0.96) between the chromogenic substrates. Our data demonstrates that an automated ETP method can be standardized between laboratories and suitable levels of imprecision achieved, using different analysers (COBAS Mira at two centres and an ACL-300R) and two thrombin substrates. This indicates that more widespread use of ETP measurements in clinical laboratories is feasible.


Synthesis of meiosis-activating sterols containing fluorine.
It is documented that specific types of sterol play a major role in the resumption of meiosis in oocytes from mice in vitro. 4,4-Dimethyl-5 alpha-cholesta-8,14,24-trien-3 beta-ol (FF-MAS) isolated from human follicular fluid and 4,4-dimethyl-5 alpha-cholesta-8,24-dien-3 beta-ol (T-MAS) isolated from bull testicular tissue, have been shown to activate (promote) meiosis in vitro. In order to evaluate the biological activity and stability of such compounds, new demethylsterol derivatives have been synthesised. Using diethylaminosulfur trifluoride (DAST) it was possible to synthesise selected delta 8, delta 14 sterols with mono and difluoro substitution at C3.


Fixation durations in scene viewing: Modeling the effects of local image features, oculomotor parameters, and task.
Scene perception requires the orchestration of image- and task-related processes with oculomotor constraints. The present study was designed to investigate how these factors influence how long the eyes remain fixated on a given location. Linear mixed models (LMMs) were used to test whether local image statistics (including luminance, luminance contrast, edge density, visual clutter, and the number of homogeneous segments), calculated for 1° circular regions around fixation locations, modulate fixation durations, and how these effects depend on task-related control. Fixation durations and locations were recorded from 72 participants, each viewing 135 scenes under three different viewing instructions (memorization, preference judgment, and search). Along with the image-related predictors, the LMMs simultaneously considered a number of oculomotor and spatiotemporal covariates, including the amplitudes of the previous and next saccades, and viewing time. As a key finding, the local image features around the current fixation predicted this fixation's duration. For instance, greater luminance was associated with shorter fixation durations. Such immediacy effects were found for all three viewing tasks. Moreover, in the memorization and preference tasks, some evidence for successor effects emerged, such that some image characteristics of the upcoming location influenced how long the eyes stayed at the current location. In contrast, in the search task, scene processing was not distributed across fixation durations within the visual span. The LMM-based framework of analysis, applied to the control of fixation durations in scenes, suggests important constraints for models of scene perception and search, and for visual attention in general.


Effect of L-DOPA/Benserazide on Propagation of Pathological α-Synuclein.
Parkinson's disease (PD) and related disorders are characterized by filamentous or fibrous structures consisting of abnormal α-synuclein in the brains of patients, and the distributions and spread of these pathologies are closely correlated with disease progression. L-DOPA (a dopamine precursor) is the most effective therapy for PD, but it remains unclear whether the drug has any effect on the formation and propagation of pathogenic abnormal α-synuclein in vivo. Here, we tested whether or not L-DOPA influences the prion-like spread of α-synuclein pathologies in a wild-type (WT) mouse model of α-synuclein propagation. To quantitative the pathological α-synuclein in mice, we prepared brain sections stained with an anti-phosphoSer129 (PS129) antibody after pretreatments with autoclaving and formic acid, and carefully analyzed positive aggregates on multiple sections covering the areas of interest using a microscope. Notably, a significant reduction in the accumulation of phosphorylated α-synuclein was detected in substantia nigra of L-DOPA/benserazide (a dopamine decarboxylase inhibitor)-treated mice, compared with control mice. These results suggest that L-DOPA may slow the progression of PD in vivo by suppressing the aggregation of α-synuclein in dopaminergic neurons and the cell-to-cell propagation of abnormal α-synuclein. This is the first report describing the suppressing effect of L-DOPA/benserazide on the propagation of pathological α-synuclein. The experimental protocols and detection methods in this study are expected to be useful for evaluation of drug candidates or new therapies targeting the propagation of α-synuclein.


Severe scoliosis associated with Costello syndrome: a case report.
Costello syndrome is characterised by dwarfism, unique cutaneous lesions, a distinct facial gestalt, and mental retardation. There have been no detailed reports of severe spinal deformities requiring surgical treatment as a complication of Costello syndrome. We report a case of a 10-year-old girl with progressive scoliosis associated with Costello syndrome. She underwent anterior release and posterior surgical correction and fusion from T5 to L2 using a third generation hook and rod system plus spinous process wiring. Congenital portal vein deficiency and coagulopathy were other major complications. At 15-month follow-up, the patient had good balance and no evidence of instrumentation failure.


Anti-inflammatory effects of linalool on ovalbumin-induced pulmonary inflammation.
Linalool is a natural product present in fruits and aromatic plants with biological activities. Researchers have reported that the inhalation of linalool exerts anti-inflammatory activities. In this study, we examined the therapeutic effects of linalool on airway inflammation and mucus overproduction in mice with allergic asthma. Oral administration of linalool significantly inhibited the levels of eosinophil numbers, Th2 cytokines and immunoglobulin E (IgE) caused by ovalbumin (OVA) exposure. Linalool exerted preventive effects against the influx of inflammatory cells and mucus hypersecretion in the lung tissues. Linalool also dose-dependently decreased the levels of inducible nitric oxide synthase (iNOS) expression and protein kinase B (AKT) activation in the lung tissues. Linalool effectively downregulated the activation of mitogen-activated protein kinases (MAPKs) and nuclear factor-κB (NF-κB) caused by OVA exposure. Furthermore, linalool exerted inhibitory effect on OVA-induced airway hyperresponsiveness (AHR). In the in vitro study, the increased secretion of MCP-1 was attenuated with linalool treatment in lipopolysaccharide (LPS)-stimulated H292 airway epithelial cells. In conclusion, linalool effectively exerts a protective role in OVA-induced airway inflammation and mucus hypersecretion, and its protective effects are closely related to the downregulation of inflammatory mediators and MAPKs/NF-κB signaling.


Antiviral activity of salt-coated materials against SARS-CoV-2.
The SARS-CoV-2 pandemic demonstrated the importance of human coronaviruses and the need to develop materials to prevent the spread of emergent respiratory viruses. Coating of surfaces with antiviral materials is a major interest in controlling spread of viruses, especially in high-risk or high-traffic areas. A number of different coatings for surfaces have been proposed, each with their own advantages and disadvantages. Here we show that simple salt coating on a range of surfaces, including a novel biomass aerogel can reduce the infectivity of SARS-CoV-2 placed onto the surface. This suggests that a simple to apply coating could be applied to a range of materials and have an antiviral effect against SARS-CoV-2, as well as other potential emerging viruses.


Regulation of cardiac specific nkx2.5 gene activity by small ubiquitin-like modifier.
The cardiac specific homeobox gene nkx2.5, a member of the nk-2 class family, plays a central role in cardiogenesis and is a target of the small ubiquitin-like modifier (SUMO). Nkx2.5 was modified by SUMO on its 51st amino acid, a lysine residue conserved across species but absent in other nk-2 members. Conversion of this lysine to an arginine (K51R) substantially reduced Nkx2.5 DNA binding and also its transcriptional activity. Unexpectedly, mutant K51R was targeted by ubiquitin. E3 ligase PIAS proteins PIAS1, PIASx, and PIASy, but not PIAS3, enhanced SUMO-1 attachment to Nkx2.5 on the primary SUMO acceptor site. SUMO-2 linkage to Nkx2.5 was catalyzed only by PIASx and not by other PIAS proteins. SUMO conjugation stabilized the formation of Nkx2.5-containing complexes that led to robust transcriptional activation. Thus, SUMO modification serves as a positive regulator for Nkx2.5 transcriptional activity.


Is Tecar Therapy Effective on Biceps Femoris and Quadriceps Rehabilitation? A Cadaveric Study.
Capacitive-resistive electric transfer therapy is an interesting rehabilitation treatment to use in musculoskeletal injuries. The purpose is to analyze the temperature change and current flow in superficial and deep biceps femoris and quadriceps tissues when applying different protocols of capacitive-resistive electric transfer therapy. Five cryopreserved cadavers (10 legs) were included in this study. Four interventions (high/low power) were performed for 5 minutes. Dynamic movements were performed to the biceps femoris and quadriceps. Superficial, middle, and deep temperature were recorded at 1-minute intervals and 5 minutes after the treatment using invasive temperature meters placed with ultrasound guidance. Low-power applications have generated a very low thermal effect and an important current flow. The high-power capacitive application achieves a greater increase in superficial temperature compared with low power (P < .001). The high-power resistive application recorded a greater increase in superficial, middle, and deep temperatures with a greater current flow compared with the other applications (P < .001). This study could serve as basic science data to justify the acceleration of the processes of muscle recovery, improving cell proliferation without increasing the temperature in acute muscle injuries and increasing the temperature and viscoelasticity of the tissues in chronic processes with this therapy.


Cytochrome P450s: mechanisms and biological implications in drug metabolism and its interaction with oxidative stress.
Cytochrome monooxygenases P450 enzymes (CYPs) are terminal oxidases, belonging to the multi-gene family of heme-thiolate enzymes and located in multiple sites of ER, cytosol and mitochondria. CYPs act as catalysts in drugs metabolism. This review highlights the mitochondrial and microsomal CYPs metabolic functions, CYPs mediated ROS generation and its feedback, bioactivation of drugs and related hypersensitivity, metabolic disposition as well as the therapeutic approaches. CYPs mediated drugs bioactivation may trigger oxidative stress and cause pathophysiology. Almost all drugs show some adverse reactions at high doses or accidental overdoses. Drugs lead to hypersensitivity reactions while metabolic predisposition to drug hypersensitivity exaggerates it. Mostly different intermediate bioactive products of CYPs mediated drug metabolism is the principal issue in this respect. On the other hand, CYPs are the main source of ROS. Their generation and feedback are of major concern of this review. Besides drug metabolism, CYPs also contribute significantly to carcinogen metabolism. Ultimately other enzymes in drug metabolism and antioxidant therapy are indispensible. Importance of this field: In a global sense, understanding of exact mechanism can facilitate pharmaceutical industries' challenge of developing drugs without toxicity. Ultimate message: This review would accentuate the recent advances in molecular mechanism of CYPs mediated drug metabolism and complex cross-talks between various restorative novel strategies evolved by CYPs to sustain the redox balance and limit the source of oxidative stress.


Magnetic resonance imaging tumor regression shrinkage patterns after neoadjuvant chemotherapy in patients with locally advanced breast cancer: Correlation with tumor biological subtypes and pathological response after therapy.
The objective of this study is to analyze magnetic resonance imaging shrinkage pattern of tumor regression after neoadjuvant chemotherapy and to evaluate its relationship with biological subtypes and pathological response. We reviewed the magnetic resonance imaging studies of 51 patients with single mass-enhancing lesions (performed at time 0 and at the II and last cycles of neoadjuvant chemotherapy). Tumors were classified as Luminal A, Luminal B, HER2+, and Triple Negative based on biological and immunohistochemical analysis after core needle biopsy. We classified shrinkage pattern, based on tumor regression morphology on magnetic resonance imaging at the II cycle, as concentric, nodular, and mixed. We assigned a numeric score (0: none; 1: low; 2: medium; 3: high) to the enhancement intensity decrease. Pathological response on the surgical specimen was classified as complete (grade 5), partial (grades 4-3), and non-response (grades 1-2) according to Miller and Payne system. Fisher test was used to relate shrinkage pattern with biological subtypes and final pathological response. Seventeen patients achieved complete response, 25 partial response, and 9 non-response. A total of 13 lesions showed nodular pattern, 20 concentric, and 18 mixed. We found an association between concentric pattern and HER2+ (p < 0.001) and mixed pattern and Luminal A lesions (p < 0.001). We observed a statistical significant correlation between concentric pattern and complete response (p < 0.001) and between mixed pattern and non-response (p = 0.005). Enhancement intensity decrease 3 was associated with complete response (p < 0.001). Shrinkage pattern and enhancement intensity decrease may serve as early response indicators after neoadjuvant chemotherapy. Shrinkage pattern correlates with tumor biological subtypes.


Anesthetic consideration for neurointerventional procedures.
Interventional neuroradiology (INR) has been a rapidly expanding and advancing clinical area during the past few decades. As the complexity and diversity of INR procedures increases, the demand for anesthesia also increases. Anesthesia for interventional neuroradiology is a challenge for the anesthesiologist due to the unfamiliar working environment which the anesthesiologist must consider, as well as the unique neuro-interventional components. This review provides an overview of the anesthetic options and specific consideration of the anesthesia requirements for each procedure. We also introduce the anesthetic management for interventional neuroradiology performed in our medical institution.


Depigmentation of oral mucosa as the earliest possible manifestation of oral submucous fibrosis in Sri Lankan preschool children.
This article reports the presentation of oral submucous fibrosis in five Sri Lankan preschool children, aged 2-3 years, with loss of pigmentation of the lips as the sole clinical feature. Oral submucous fibrosis has not been reported in this age group of children. The five 2-3 year olds did not display any classical features of oral submucous fibrosis, due to the disease having been detected at a very early stage. The present study attempts to establish that depigmentation of the lips and oral mucosa is perhaps the earliest feature to develop in the natural history of oral submucous fibrosis. The differential diagnosis of oral mucosal depigmentation relevant to these cases is also discussed. Previously-reported cases of oral submucous fibrosis in children are reviewed.


Third- and fourth-order elasticities of biological soft tissues.
In the theory of weakly nonlinear elasticity, Hamilton et al. [J. Acoust. Soc. Am. 116, 41-44 (2004)] identified W=muI(2)+(A/3)I(3)+DI(2) (2) as the fourth-order expansion of the strain-energy density for incompressible isotropic solids. Subsequently, much effort focused on theoretical and experimental developments linked to this expression in order to inform the modeling of gels and soft biological tissues. However, while many soft tissues can be treated as incompressible, they are not in general isotropic, and their anisotropy is associated with the presence of oriented collagen fiber bundles. Here the expansion of W is carried up to fourth order in the case where there exists one family of parallel fibers in the tissue. The results are then applied to acoustoelasticity, with a view to determining the second- and third-order nonlinear constants by employing small-amplitude transverse waves propagating in a deformed soft tissue.


Combined analysis of chemical bonding in a Cu(II) dimer using QTAIM, Voronoi tessellation and Hirshfeld surface approaches.
Interaction of 1-(1H-pyrazol-5-yl)ethanone oxime (H2PzOx) with copper(II) chloride in the presence of pyridine afforded a binuclear discrete [Cu2(HPzOx)2Cl2py2] complex, which was characterized by Fourier transform-IR and electron paramagnetic resonance (EPR) spectra, magnetochemistry and high-resolution X-ray diffraction experiments. Multipole refinement of X-ray diffraction data and density-functional theory (DFT) calculations of an isolated molecule allowed charge and spin distributions to be obtained for this compound. Magnetochemistry data, EPR spectra and DFT calculations of an isolated molecule show antiferromagnetic coupling between copper(II) ions. The spin distribution suggests an exchange pathway via the bridging pyrazole ring in the equatorial plane of the CuN4Cl coordination polyhedron, thus providing support for the classical superexchange mechanism; the calculated value of the magnetic coupling constant -2J is equal to 220 cm(-1), which compares well with the experimental value of 203 ± 2 cm(-1). Chemical connectivity was derived by Bader's 'quantum theory of atoms in molecules' and compared with Voronoi tessellation and Hirshfeld surface representations of crystal space. All methodologies gave a similar qualitative and semi-quantitative description of intra- and intermolecular connectivity.


Disturbances in the propagation of the slow wave during acute local ischaemia in the feline small intestine.
The normal aborad propagation of the slow wave in the small intestine is easily distorted by pacing, hypoxia or transection. We studied whether acute local ischaemia would also induce serious conduction disturbances and ectopic pacemaking. After general anaesthesia and a mid-abdominal incision, a multi-electrode array of 240 extracellular electrodes was positioned on the serosal surface of an exteriorized intestinal loop. Simultaneous recordings of all 240 surface electrodes was performed during a control period and for 5-10 min following local acute arterial occlusion. After the experiments activation maps were constructed describing the pattern of propagation of the slow waves. During control periods, the activation maps showed homogeneous aborad conduction of the slow wave. During acute ischaemia, local areas of inexcitability developed rapidly, merging together to form lines of conduction block. This in turn often provoked the appearance of subsidiary ectopic pacemakers. The location of the conduction blocks as well as that of ectopic pacemakers was highly variable and could disappear and reappear at other sites. Within minutes, acute ischaemia disturbed the organized homogeneous aborad propagation of the slow wave leading to pronounced inhomogeneous depression of conduction, local inexcitability, conduction block and the appearance of subsidiary pacemakers.


Chemical reactions and applications of the reductive surface of porous silicon.
The chemical reactivity of freshly prepared porous silicon is similar to that of a reducing agent on the surface of the nanocrystallites. Ag+ spontaneously reduces to form Ag0 granular coatings on the surface of porous silicon at the expense of the oxidation of silicon hydride and silicon. Atomic Force Microscopy shows that the thickness and topography of the Ag0 coating depend on the concentration of Ag+ with the porous silicon surface being the limiting reagent. In-situ Raman Spectroscopy shows an Ag layer on the silicon and Si:O layer immediately after etching and exposure to Ag+ and O2 respectively. Ag0 coated on the surface and in the pores of the porous silicon proves to be an excellent material for Surface Enhanced Raman Spectroscopy and the natural low electron affinity on the surface of porous silicon replaces the need for a negative bias to prepare very stable diamond coatings on the surface of silicon.


Injuries due to violence: workers' compensation claims among nurses in Ontario.
1. From 1987 to 1989 in Ontario, Canada, there were 100 or more allowed workers' compensation claims among nurses for injuries due to violence. The annual rates for such claims were higher among male nurses (13.9 per 1000) than among female nurses (1.4 per 1000). 2. Compared to the general Ontario work force, the rates for such claims were significantly higher among both male and female nurses. 3. These compensation data are consistent with surveys showing that nurses and other health care workers are at risk for violent injury in the workplace. 4. The compensation data likely underestimate the extent of the problem, because no statistics are available for denied claims or claims with no lost time, and many assaults are unreported. Measures for prevention and increasing awareness are required.


Uncovering the dynamics of cellular responses induced by iron-carbohydrate complexes in human macrophages using quantitative proteomics and phosphoproteomics.
Iron-carbohydrate complexes are widely used to treat iron deficiencies. Macrophages play a crucial role in the uptake and fate of these nanomedicines, however, how complexed iron carbohydrates are taken up and metabolized by macrophages is still not fully understood. Using a (phospho-)proteomics approach, we assessed differences in protein expression and phosphorylation in M2 macrophages triggered by iron sucrose (IS). Our results show that IS alters the expression of multiple receptors, indicative of a complex entry mechanism. Besides, IS induced an increase in intracellular ferritin, the loss of M2 polarization, protective mechanisms against ferroptosis, and an autophagic response. These data indicate that macrophages can use IS as a source of iron for its storage and later release, however, the excess of iron can cause oxidative stress, which can be successfully regulated by the cells. When comparing IS with ferric carboxymaltose (FCM) and iron isomaltoside-1000 (IIM), complexes with a higher carbohydrate ligand stability, we observed that FCM and IIM are metabolized at a slower rate, and trigger M2 polarization loss to a lower extent. These results indicate that the surface characteristics of the iron-carbohydrate complexes may influence the cell responses. Our data show that the application of (phospho-)proteomics can lead to a better understanding of metabolic processes, including the uptake, biodegradation and bioavailability of nanomedicines.


[Radiation therapy of nasopharyngeal carcinoma. Retrospective study for the assessment of long-term results].
During the years from 1967 to 1986, 90 patients with nasopharyngeal carcinomas were irradiated at the Radiologic Hospital of Bonn University. The median overall survival time was 4.3 years which corresponded to 23% of the statistical life expectancy of the patients. 66% were still alive after two years and 46.5% after five years. Compared to the overall group, the prognosis was significantly worse in case of highly differentiated, keratinizing squamous cell carcinomas, penetration of the primary tumor into the base of the skull, or certain symptoms as ophthalmo-neurologic troubles, headaches, loss of body weight, night sweat, or fever. After partial tumor excision performed prior to irradiation or complete remission following to radiotherapy, the therapy results were better than the average with median survival times of about eleven years.


Chief nursing officer for Ireland aims to 'bring nurses together'.
WHEN IRELAND'S chief nursing officer (CNO) Siobhan O'Halloran was appointed to her post two years ago this month, she was determined to join nurses together, not just between the different nursing branches but geographically too.


Two cases of trisomy 19 as a sole chromosomal abnormality in myeloid disorders.
Trisomy 19 is frequently encountered in cases of chronic myeloid leukemia (CML) as a secondary abnormality: however, trisomy 19 rarely occurs as a sole chromosomal abnormality and, to date, it has only been reported in 48 hematopoietic malignancies, 1 case of adenocarcinoma and 1 case of astrocytic tumor. Here, we report two additional cases of trisomy 19 as a sole karyotypic aberration in myeloid malignancies. One of these cases involved a 6-month-old male who was diagnosed with acute myeloid leukemia minimally differentiated. His karyotype was 47,XY,+19[20]. He expired 5 days after diagnosis. Another case occurred in an 80-yr-old female who had refractory anemia with excess blasts. Her karyotype was 47,XX,+19[16]/46,XX[4]. Four months later, her peripheral blood smears suggested that the disease had progressed, but she refused further evaluation. Based on a review of the existing literature and the results of this report, trisomy 19 not only as a secondary abnormality but also as a sole karyotypic aberration is strongly associated with myeloid disorder; however, it is not preferentially found in specific FAB subgroups of myelodysplasic syndrome or acute myeloid leukemia.


Perforating dermatoses: a review and report of four cases.
Perforating dermatoses, an often overlooked entity comprised of Kyrle's disease, perforating folliculitis, reactive perforating collagenosis, elastosis perforans serpiginosa, and acquired perforating dermatosis, are succinctly described, focusing attention on their clinical features, histopathology, treatment, and pathogenesis. The literature on these facets has been extensively reviewed. In addition, three fresh cases of Kyrle's and one of perforating folliculitis have been incorporated to illustrate these conditions.


The Slx4-Dpb11 scaffold complex: coordinating the response to replication fork stalling in S-phase and the subsequent mitosis.
Replication fork stalling at DNA lesions is a common problem during the process of DNA replication. One way to allow the bypass of these lesions is via specific recombination-based mechanisms that involve switching of the replication template to the sister chromatid. Inherent to these mechanisms is the formation of DNA joint molecules (JMs) between sister chromatids. Such JMs need to be disentangled before chromatid separation in mitosis and the activity of JM resolution enzymes, which is under stringent cell cycle control, is therefore up-regulated in mitosis. An additional layer of control is facilitated by scaffold proteins. In budding yeast, specifically during mitosis, Slx4 and Dpb11 form a cell cycle kinase-dependent complex with the Mus81-Mms4 structure-selective endonuclease, which allows efficient JM resolution by Mus81. Furthermore, Slx4 and Dpb11 interact even prior to joining Mus81 and respond to replication fork stalling in S-phase. This S-phase complex is involved in the regulation of the DNA damage checkpoint as well as in early steps of template switch recombination. Similar interactions and regulatory principles are found in human cells suggesting that Slx4 and Dpb11 may have an evolutionary conserved role organizing the cellular response to replication fork stalling.


Scope and Mechanism of a True Organocatalytic Beckmann Rearrangement with a Boronic Acid/Perfluoropinacol System under Ambient Conditions.
Catalytic activation of hydroxyl functionalities is of great interest for the production of pharmaceuticals and commodity chemicals. Here, 2-alkoxycarbonyl- and 2-phenoxycarbonyl-phenylboronic acid were identified as efficient catalysts for the direct and chemoselective activation of oxime N-OH bonds in the Beckmann rearrangement. This classical organic reaction provides a unique approach to prepare functionalized amide products that may be difficult to access using traditional amide coupling between carboxylic acids and amines. Using only 5 mol % of boronic acid catalyst and perfluoropinacol as an additive in a polar solvent mixture, the operationally simple protocol features mild conditions, a broad substrate scope, and a high functional group tolerance. A wide variety of diaryl, aryl-alkyl, heteroaryl-alkyl, and dialkyl oximes react under ambient conditions to afford high yields of amide products. Free alcohols, amides, carboxyesters, and many other functionalities are compatible with the reaction conditions. Investigations of the catalytic cycle revealed a novel boron-induced oxime transesterification providing an acyl oxime intermediate involved in a fully catalytic nonself-propagating Beckmann rearrangement mechanism. The acyl oxime intermediate was prepared independently and was subjected to the reaction conditions. It was found to be self-sufficient; it reacts rapidly, unimolecularly without the need for free oxime. A series of control experiments and 18O labeling studies support a true catalytic pathway involving an ionic transition structure with an active and essential role for the boronyl moiety in both steps of transesterification and rearrangement. According to 11B NMR spectroscopic studies, the additive perfluoropinacol provides a transient, electrophilic boronic ester that is thought to serve as an internal Lewis acid to activate the ortho-carboxyester and accelerate the initial, rate-limiting step of transesterification between the precatalyst and the oxime substrate.


In-Hospital Cardiac Arrest (IHCA) and Outcomes in Patients Admitted With COVID-19 Infection.
During the COVID-19 pandemic, many patients are hospitalized, and those suffering from in-hospital cardiac arrest (IHCA) have been previously reported to have poor outcomes. This is a single-center, retrospective, observational study conducted at the Veterans Affairs Medical Center, Washington, DC, USA. The inclusion criteria were: patients admitted to the hospital with a diagnosis of COVID-19 who underwent cardiopulmonary resuscitation (CPR) for IHCA. Patients were labeled as COVID-19 positive based on a laboratory-confirmed positive polymerase chain reaction test. Patients with do-not-resuscitate (DNR) orders, those who were made comfort care, or enrolled in hospice were excluded. The study was approved by the hospital's institutional review board. A total of 155 patients with COVID-19 infection were admitted; 145/155 (93.5%) admitted to the medical floor and 10/155 (6.5%) to the medical intensive care unit (MICU). 36/145 (24.8%) floor patients were upgraded to MICU. Of the 46 patients treated in MICU, 17/46 (36.9%) were excluded for DNR status. From the remaining 29/46 (63.1%) patients, 19/29 (65.5%) patients survived, and 10/29 (34.5%) patients had IHCA. All 10/10 (100%) died after CPR without return of spontaneous circulation (ROSC). The initial rhythm was non-shockable in all patients, with pulseless electrical activity (PEA) in 7/10 (70%) and asystole in 3/10 (30%) patients. Patients with COVID-19 infection who had an IHCA and underwent CPR had a 0% survival at our hospital. Discussions on advanced care options, especially CPR, with COVID-19 patients and their families, are important as the overall prognosis after CPR for IHCA is poor.


Multiple cycles of preconditioning cause loss of protection in open-chest rabbits.
Although single or multiple bursts of ischemic preconditioning have been shown to protect against myocardial necrosis, the frequency-dependency of the protection afforded by multiple stimuli has not yet been systematically studied in the anesthetized animal. The aim of the present study was to characterize the effect of increasing numbers of preconditioning stimuli (5 min ischemia plus 10 min reperfusion) in a collateral-deficient species in vivo. Rabbits were anesthetized and divided into groups (n = 5-7/group) which were subjected to 0, 1, 2, 4, 6 or 8 cycles of preconditioning (each comprising 5 min of regional ischemia plus 10 min reperfusion) followed by 45 min of regional ischemia and 2 h reperfusion. An additional group, serving as a control, was subjected to eight cycles of preconditioning without a subsequent 45 min of regional ischemia. Infarct size (I) and risk zones (R) were delineated with the aid of tetrazolium staining and fluorescent particles and the I/R ratio was expressed as a percentage. Mean infarct size in the control group which had no preconditioning was 59.8 +/- 4.0%. This was reduced to 22.2 +/- 2.9%, 19.5 +/- 4.1% and 23.3 +/- 3.4% by one, two and four cycles of preconditioning. However, when the number of preconditioning cycles was increased to six or eight protection declined with infarct sizes of 41.8 +/- 6.9% (P < 0.05 v zero preconditioning control group) and 47.1 +/- 7.6% (N.S. v zero preconditioning control group). In the group subjected to eight cycles of preconditioning without subsequent ischemia, infarction was not detected. In conclusion, in the anesthetized rabbit, beyond 4 cycles, protection against infarction diminishes with increasing numbers of preconditioning cycles.


Chronic Otitis Externa Secondary to Tympanic Membrane Electrode Placement in Rhesus Macaques (Macaca mulatta).
Otitis externa (OE) is a condition that involves inflammation of the external ear canal. OE is a commonly reported condition in humans and some veterinary species (for example, dogs, cats), but has not been reported in the literature in macaques. Here, we present a case series of acute and chronic OE likely precipitated by abrasion of the ear canal with a tympanic membrane electrode in 7 adult male rhesus macaques (Macaca mulatta). All animals displayed purulent, mucinous discharge from 1 or both ears with 3 macaques also displaying signs of an upper respiratory tract (URT) infection during the same period. A variety of diagnostic and treatment options were pursued including consultation with an otolaryngologist necessitated by the differences in response to treatment in macaques as compared with other common veterinary species. Due to the nature of the studies in which these macaques were enrolled, standard audiological testing was performed before and after OE, including tympanometry, auditory brainstem responses (ABRs), and distortion product otoacoustic emissions (DPOAEs). After completion of study procedures, relevant tissues were collected for necropsy and histopathology. Impaired hearing was found in all macaques even after apparent resolution of OE signs. Necropsy findings included abnormalities in the tympanic membrane, ossicular chain, and middle ear cavity, suggesting that the hearing impairment was at least partly conductive in nature. We concluded that OE likely resulted from mechanical disruption of the epithelial lining of the ear canal by the ABR electrode, thereby allowing the development of opportunistic infections. OE, while uncommon in macaques, can affect them and should be included as a differential diagnosis of any macaque presenting with otic discharge and/or auricular discomfort.


A simple method of evaluation of jaundice in the newborn.
This paper evaluates a simple tool, the icterometer, in assessing jaundice in the newborn. The instrument consists of a perspex scale with yellow stripes of increasing intensity, numbered 1-5, alternating with transparent areas through which the infant's blanched skin colour can be seen and compared with the coloured stripes. The scale was found to be useful for more objective screening of neonatal jaundice, particularly in decreasing the number of blood samples to be taken for serum bilirubin. The present study suggests that serum bilirubin estimation can be avoided when the icterometer readings on the face are 3 or less, unless there is a rapid rise in jaundice within 24-36 h. However, a reading on the sole of even 1 is significant and requires assessment by trained staff for blood sampling and/or phototherapy. The instrument may also be useful to peripheral staff in developing countries when deciding on referral to specialist centres and to staff in specialist centres for screening cases of neonatal jaundice and decreasing the number of blood samples.


Automated Identification of Patent Ductus Arteriosus Using a Computer Vision Model.
Patent ductus arteriosus (PDA) is a vascular defect common in preterm infants and often requires treatment to avoid associated long-term morbidities. Echocardiography is the primary tool used to diagnose and monitor PDA. We trained a deep learning model to identify PDA presence in relevant echocardiographic images. Echocardiography video clips (n = 2527) in preterm infants were reviewed by a pediatric cardiologist and those relevant to PDA diagnosis were selected and labeled (PDA present/absent/indeterminate). We trained a convolutional neural network to classify each echocardiography frame of a clip as belonging to clips with or without PDA. A novel attention mechanism that aggregated predictions for all frames in each clip to obtain a clip-level prediction by weighting relevant frames. In early model iterations, we discovered training with color Doppler echocardiography clips produced the best performing classifier. For model training and validation, 1145 such clips from 66 patients (661 PDA+ clips, 484 PDA- clips) were used. Our best classifier for clip level performance obtained sensitivity of 0.80 (0.83-0.90), specificity of 0.77 (0.62-0.92) and AUC of 0.86 (0.83-0.90). Study level performance obtained sensitivity of 0.83 (0.72-0.94), specificity of 0.89 (0.79-1.0) and AUC of 0.93 (0.89-0.98). Our novel deep learning model demonstrated strong performance in classifying echocardiography clips with and without PDA. Further model development and external validation are warranted. Ultimately, integration of such a classifier into auto detection software could streamline PDA imaging workflow. This work is the first step toward semi-automated, bedside detection of PDA in preterm infants.


[Value of promoter methylation of RASSF1A, p16, and DAPK genes in induced sputum in diagnosing lung cancers].
To determine the aberrant methylation status of RASSF1A,p16 and DAPK gene promoter region in induced sputum from lung cancer patients and the value of their combined detection in diagnosing lung cancers. Methylation-specific PCR (MSP) was used to detect the promoter methylation status of RASSF1A, p16, and DAPK genes in induced sputum and pathological tissues from 82 patients with lung cancers and 25 patients with pulmonary benign lesion. We also analyzed the relation between methylation status and clinical pathological data. The positive rates of promoter methylation of RASSF1A, p16, and DAPK genes in pathological tissues from patients with lung cancers were 63.4%, 59.8%, and 58.5%, respectively,and those in induced sputum were 54.9%, 48.8%, and 51.2%, respectively. The promoter methylation of RASSF1A,p16, and DAPK genes were not detected in patients with pulmonary benign lesion. There was a significant difference between the lung cancer group and pulmonary benign lesion group (P<0.05). The methylation rate of RASSF1A gene was significantly lower in the middle and high differentiation and non-metastastic lymph node of lung cancer tissues than that in the poor differentiation and the metastatic lymph node of lung cancer tissues(P<0.05), and was not correlated with age, sex, smoking index, clinical stage, and pathological types.The methylation rate of p16, and DAPK genes was not significantly correlated with all the above mentioned factors (P>0.05). The methylation rate of joint detecting RASSF1A, p16, and DAPK genes was 73.2%. Joint detection for promoter hypermethylation of RASSF1A, p16, and DAPK genes in induced sputum may be used as a simple and effective index of the diagnosis and prognose of lung cancers, and can improve the positive rate.


[Effects on erectile function of transplanted major pelvic ganglion into the corpus cavernosum of adult rats with bilateral cavernous nerve injury].
To investigate the effects on erectile function of transplanted major pelvic ganglion into the corpus cavernosum of adult male rats undergoing transection of bilateral cavernous nerves. Twenty-six male Sprague-Dawley rats (3 - 4 month-old and 300 - 400 g/each) were divided into 2 groups: experimental group (transection of bilateral cavernous nerves and transplantation of left ganglion into left crus of penis, n = 16) and control group (transection of bilateral cavernous nerves only, n = 10). Erectile function was measured by injecting APO, and intracavernous pressure was measured 1 and 3 months afterwards by electric-stimulating the right major pelvic ganglion or the left crus. Half animals in each group were sacrificed 1 and 3 months afterwards for detecting nNOS-containing nerve fibers of corpus cavernosum. Electron microscopy of the implanted area was performed to assess neuronal survival. Both of the two groups have no erectile response to APO injection. Electrostimulation on the right major pelvic ganglion and left crus failed to produce erection in experimental group. The mean pressure changes in the two groups, measured by stimulating the left crus, were (9.41 +/- 3.20) and (4.16 +/- 2.58) cmH(2)O 1 month afterwards, and (13.67 +/- 4.18) and (5.09 +/- 2.74) cmH(2)O 3 months afterwards, respectively (P < 0.05). An increased number of nNOS-containing nerve fibers in left crus was detected in experimental group 1 and 3 months later, compared with control one (218.7 +/- 24.5, 18.0 +/- 3.7; 183.2 +/- 19.7, 19.0 +/- 3.8; P < 0.05). Ultrastructure examination by transmission electron microscope confirmed the survival of the implanted ganglion. Major pelvic ganglion can survive in the corpus cavernosum, and it has significant effects on the number of nNOS-containing nerve fibers and the alteration of intracavernous pressure.


miR-145 sensitizes breast cancer to doxorubicin by targeting multidrug resistance-associated protein-1.
Multidrug resistance-associated protein 1 (MRP1) is an important efflux transporter and overexpression of MRP1 usually leads to chemoresistance in breast cancer. Here, we found MRP1 overexpressed in human breast cancer tissues and breast cancer cell lines (compared with normal breast tissues and cell line, respectively). And MRP1 level increased in doxorubicin resistant MCF-7 cells compared with parental MCF-7 cells. Increasing evidences suggest microRNAs (miRNAs) influence chemotherapy response. We found miR-145 level decreased in human breast cancer tissues, breast cancer cell lines and doxorubicin resistant MCF-7 cells, and inversely correlated with MRP1 expression level. In the process of constructing MCF-7 doxorubicin resistant cell line, escalating doxorubicin markedly decreased miR-145 level, following by increased MRP1 level. Further study showed, miR-145 suppressed MRP1 expression by directly targeting MRP1 3'-untranslated regions. Overexpression of miR-145 sensitized breast cancer cells to doxorubicin in vitro and enhanced to doxorubicin chemotherapy in vivo through inducing intracellular doxorubicin accumulation via inhibiting MRP1. Taken together, our study revealed miR-145 sensitizes breast cancer to doxorubicin by targeting MRP1 and indicated the potential application in developing MRP1 inhibitor.


Homologous Recombination Subpathways: A Tangle to Resolve.
Homologous recombination (HR) is an essential pathway for DNA double-strand break (DSB) repair, which can proceed through various subpathways that have distinct elements and genetic outcomes. In this mini-review, we highlight the main features known about HR subpathways operating at DSBs in human cells and the factors regulating subpathway choice. We examine new developments that provide alternative models of subpathway usage in different cell types revise the nature of HR intermediates involved and reassess the frequency of repair outcomes. We discuss the impact of expanding our understanding of HR subpathways and how it can be clinically exploited.


Determination of quinolone antibiotics in honey by pH-induced natural deep eutectic solvent combined with vortex-assisted dispersive liquid-liquid microextraction.
A green, fast, and efficient pH-induced natural deep eutectic solvent combined with vortex-assisted dispersive liquid-liquid microextraction method (pH-NADES-VA-DLLME) followed by HPLC was established for determination of ofloxacin (OFL), ciprofloxacin (CIP) and enrofloxacin (ENR) in honey. In this method, NaOH, as an emulsifier, can increase the contact area between the NADES and the sample solution, which can efficiently improve the extraction efficiency of the analytes. Moreover, HCl acts as the phase separation agent without centrifugation in the process, which can greatly enhance the efficiency of the sample analysis process. In addition, the main factors affecting the extraction effect were optimized by single factor experiments. Under the optimal conditions, the limits of detection (LODs), the limits of quantification (LOQs) and recoveries were in the range of 0.004-0.015 μg mL-1, 0.012-0.050 μg mL-1, and 98.0-112.5%, respectively. The RSD values of intra-day and inter-day precisions were no more than 5.5% and 6.0%, respectively. The developed method was successfully applied to determine the three quinolone antibiotics in honey.


Effects of drugs on uric acid in man.
In this review the drugs capable of increasing or lowering the serum urate concentration are considered with regard to mechanism of action and significance of the effect, where known. Several hypouricemic agents, probenecid, sulfinpyrazone, and allopurinol, are considered in further detail because of their major clinical importance. No effort has been made, however, to summarize the relative clinical indications for each agent. In addition, in those cases where specific details could not be included because of limitation of space, the appropiate reference has been given.


Comparison of Indoor Air Quality between 2 Ventilation Strategies in a Facility Housing Rhesus Macaques (Macaca mulatta).
Adequate indoor-air quality (IAQ)--defined by the temperature, relative humidity, and the levels of carbon dioxide, small particles, and total volatile organic compounds (TVOC)--is crucial in laboratory animal facilities. The ventilation standards for controlling these parameters are not well defined. This study assessed the effect of 2 ventilation strategies on IAQ in 2 rooms housing rhesus macaques (Macaca mulatta). We hypothesized that using a demand-controlled ventilation (DCV) system with a baseline ventilation rate of less than 3 fresh-air changes per hour (ACH) would maintain IAQ comparable to or better than the traditional constant flow rate (CFR) system at 12 fresh ACH. During a 60-d study period, each of the 2 rooms operated 30 d on DCV and 30 d on CFR ventilation. In both rooms, temperatures remained more consistently within the established setpoint during the DCV phase than during the CFR phase. Relative humidity did not differ significantly between rooms or strategies. CO₂ was lower during the CFR phase than DCV phase. Small-particle and TVOC levels were lower during CFR in the larger (3060 ft(3)) room but not the smaller (2340 ft(3)) room. During the DCV phase, the larger room was at the baseline airflow rate over 99% of the time and the smaller room over 96% of the time. The DCV strategy resulted in a baseline airflow rate of less than 3 ACH, which in turn provided acceptable IAQ over 96% of the time; higher ventilation rates were warranted only during sanitation periods.


The 22nd annual prostate cancer foundation scientific retreat report.
The 22nd Annual Prostate Cancer Foundation (PCF) Scientific Retreat was convened in Washington, D.C. from October 8 to 10, 2015. This event is the foremost scientific conference in the world focusing on basic, translational, and clinical prostate cancer research with the highest potential for accelerating the understanding of prostate cancer biology and improving the lives and outcomes of prostate cancer patients. Topics highlighted during the 2015 Retreat included: (i) new strategies and treatments for localized high-risk, hormone-naïve, oligometastatic, castrate-resistant, and treatment-refractory prostate cancer settings; (ii) the biology and genomics of tumor heterogeneity and tumor evolution; (iii) new understandings on the mechanisms and targeting of oncogenic drivers of prostate cancer; (iv) bioengineering of novel therapies and drug delivery methods; (v) innovative approaches to tumor immunotherapy; (vi) emerging molecular imaging technologies with improved sensitivity and specificity; and (vii) advancements in prognostic and predictive biomarkers and precision medicine strategies. Prostate 76:1037-1052, 2016. © 2016 Wiley Periodicals, Inc.


Metal-Organic Framework-Derived FeCo-N-Doped Hollow Porous Carbon Nanocubes for Electrocatalysis in Acidic and Alkaline Media.
Metal-organic frameworks (MOFs) are ideal precursors/ templates for porous carbons with homogeneous doping of active components for energy storage and conversion applications. Herein, metalloporphyrinic MOFs, PCN-224-FeCo, with adjustable molar ratio of FeII /CoII alternatively residing inside the porphyrin center, were employed as precursors to afford FeCo-N-doped porous carbon (denoted as FeCo-NPC) by pyrolysis. Thanks to the hollow porous structure, the synergetic effect between highly dispersed FeNx and CoNx active sites accompanied with a high degree of graphitization, the optimized FeCo2 -NPC-900 obtained by pyrolysis at 900 °C exhibits more positive half-wave potential, higher diffusion-limited current density, and better stability than the state-of-the-art Pt/C, under both alkaline and acidic media. More importantly, the current synthetic approach based on MOFs offers a rational strategy to structure- and composition-controlled porous carbons for efficient electrocatalysis.


Time for a Measurement Check-Up: Testing the Couple's Satisfaction Index and the Global Measure of Sexual Satisfaction Using Structural Equation Modeling and Item Response Theory.
Relationship and sexual satisfaction are two central outcomes in the study of relationships and are commonly used in both academia and applied practice. However, relationship and sexual satisfaction measures infrequently undergo specific psychometric investigation. Ensuring that measures display strong psychometric performance is an important but under-tested element of replication that has come under more scrutiny lately, and adequate measurement of constructs is an important auxiliary assumption underpinning theory-testing empirical work. A measurement check-up was conducted, including Confirmatory Factor Analysis (CFA) to test factorial validity, measurement invariance to test for group comparability, and Item Response Theory (IRT) to assess the relationship between latent traits and their items/indicators. This format was used to evaluate the psychometric properties of the Couple's Satisfaction Index (CSI) and the Global Measure of Sexual Satisfaction (GMSEX), two commonly used scales of relationship and sexual satisfaction with a sample of 640 midlife (40-59 years old) married Canadians who were recruited by Qualtrics Panels. Results of CFA suggested that both models were satisfactory. Invariance testing provided robust support for intercept invariance across all the groupings tested. IRT analysis supported the CSI and GMSEX, however, there was evidence that the GMSEX provided somewhat less information for those high on sexual satisfaction. This measurement check-up found that the CSI and GMSEX were reasonably healthy with some caveats. Implications are discussed in terms of replicability and meaning for scholars and practitioners.


A dark green fluorescent protein as an acceptor for measurement of Förster resonance energy transfer.
Measurement of Förster resonance energy transfer by fluorescence lifetime imaging microscopy (FLIM-FRET) is a powerful method for visualization of intracellular signaling activities such as protein-protein interactions and conformational changes of proteins. Here, we developed a dark green fluorescent protein (ShadowG) that can serve as an acceptor for FLIM-FRET. ShadowG is spectrally similar to monomeric enhanced green fluorescent protein (mEGFP) and has a 120-fold smaller quantum yield. When FRET from mEGFP to ShadowG was measured using an mEGFP-ShadowG tandem construct with 2-photon FLIM-FRET, we observed a strong FRET signal with low cell-to-cell variability. Furthermore, ShadowG was applied to a single-molecule FRET sensor to monitor a conformational change of CaMKII and of the light oxygen voltage (LOV) domain in HeLa cells. These sensors showed reduced cell-to-cell variability of both the basal fluorescence lifetime and response signal. In contrast to mCherry- or dark-YFP-based sensors, our sensor allowed for precise measurement of individual cell responses. When ShadowG was applied to a separate-type Ras FRET sensor, it showed a greater response signal than did the mCherry-based sensor. Furthermore, Ras activation and translocation of its effector ERK2 into the nucleus could be observed simultaneously. Thus, ShadowG is a promising FLIM-FRET acceptor.


Stochastic Fixed Point Optimization Algorithm for Classifier Ensemble.
This paper considers a classifier ensemble problem with sparsity and diversity learning, which arises in the field of machine learning, and shows that the classifier ensemble problem can be formulated as a convex stochastic optimization problem over the fixed point set of a quasi-nonexpansive mapping. Specifically, for such a problem, this paper proposes an algorithm referred to as the stochastic fixed point optimization algorithm and performs a convergence analysis for three types of step size: 1) constant step size; 2) decreasing step size; and 3) a step size computed by line searches. In the case of a constant step size, the results indicate that a sufficiently small constant step size allows a solution to the problem to be approximated. In the case of a decreasing step size, conditions are shown under which the algorithm converges in probability to a solution. For the third case, a variation of the basic proposed algorithm also achieves convergence in probability to a solution. The high classification accuracies of the proposed algorithms are demonstrated through numerical comparisons with the conventional algorithm.


Central diabetes insipidus as the inaugural manifestation of Langerhans cell histiocytosis: natural history and medical evaluation of 26 children and adolescents.
Isolated central diabetes insipidus (CDI) can be the first manifestation of Langerhans cell histiocytosis (LCH), creating diagnostic dilemmas such as dysgerminoma and other inflammatory lesions. In 2010, the French national LCH registry had enrolled 1236 LCH patients under 18 yr of age. Isolated CDI was the initial presentation of LCH in 26 patients. We reviewed their clinical and magnetic resonance imaging (MRI) features. Median age at the diagnosis of CDI was 9.6 yr (1.8-16.3), and median follow-up after CDI diagnosis was 9.9 yr (3.5-26.6). In addition to CDI, two patients had visual field defects, four had secondary amenorrhea, and 11 had anterior pituitary deficiency. Cerebral imaging (including computed tomography in two cases), performed in 22 patients within 3 months of CDI diagnosis, showed pituitary stalk thickening in 14 patients, which was moderate (3.0-7 mm) in nine cases and marked (>7 mm) in five cases. In eight cases, the lesion extended to the floor of the third ventricle. One child with LCH presented with a mild enlarged sellar content. During follow-up, 22 patients developed extrapituitary involvement, mainly of bone (n = 15), lung (n = 9), and skin (n = 9). Pituitary biopsy was performed in eight cases and was conclusive in six cases. Pituitary stalk thickening can be observed in LCH as well as lesions extending to the floor of the third ventricle. In all cases but one, the intrasellar content was not enlarged. Long-term follow-up with close attention to bone, skin, and lung disorders may lead to the diagnosis of LCH.


Variable globin chain synthesis in mouse erythroleukemia cells.
Various mouse erythroleukemia cell lines show unique responses to chemical inducers. Lines 745 and 707, from DBA/2 mice, produced 25%--48% beta-minor and 78%--52% beta-major globin following culture with DMSO. Butyric acid treatment led to approximately 40% beta-minor globin, while induction with hemin resulted in over 80% beta-minor synthesis. Line FSD was developed independently. DMSO induction led to less than 10% beta-minor globin, while hemin and butyric acid both resulted in approximately 40% beta-minor synthesis. T3C12 and 5000 originated in DDD mice. With these lines all inducers led to only beta-major and no beta-minor synthesis. The inducers did not influence protein stability or initiation of globin synthesis. Translation of poly A-containing cytoplasmic RNA in a wheat germ cell-free system led to proportions of beta-minor that were the same as those seen in the intact cells. Thus regulation of the type of globin chain produced in erythroleukemia cells following culture with several inducing agents occurs at either the level of gene transcription or posttranslational processing, or by growth of a selected cell population.


The male abdominal glands of Leucophaea maderae: chemical identification of the volatile secretion and sex pheromone function.
In Leucophaea maderae, male calling behavior involves the release of a sex pheromone from the abdominal sternal glands. An extract of sternal glands attracted conspecific females over a distance. The compounds present were identified as hydroxy-3-butan-2-one, (2R, 3R)-butanediol, senecioic acid, and (E)-2-octenoic acid. The same components are also present in male tergal glands. The identified compounds were tested on their own and in mixtures. Their biological function is discussed.


Reactive lymphadenopathies.
Reactive lymphadenopathies often pose a diagnostic problem. The distinction of a reactive from a neoplastic lymph node requires the application of general histologic criteria that traditionally have involved the evaluation of cytologic features including cellular polymorphism v monomorphism and the presence or absence of cytologic atypia. Although these cytologic criteria remain valid, they are not inviolate and exceptions exist that may result in diagnostic ambiguity. In addition, the interpretation of a reactive process in a lymph node is predicated on the evaluation of the dominant histologic architectural pattern and on a systematic approach to the diagnosis. The patterns specifically include whether the nodal architecture is predominantly diffuse, mixed interfollicular and follicular, follicular, or sinusoidal. Under each of these dominant architectural configurations, a host of benign reactive diagnoses may be assigned. An awareness of the various diagnostic categories for each major histologic pattern, the range and subtleties of their histologic expression, and the application of new methods, such as immunology to determine clonality, have resulted in simultaneous narrowing of the diagnostic possibilities and expansion of our comprehension of the reactive lymphadenopathies.