Migraine-like visual phenomena associated with cerebral venous thrombosis.
Two adults presented with new-onset migrainous-type visual disturbances and had angiographically demonstrated filling defects near the torcular Herophili. Neither patient had a visual field deficit nor cerebral computed tomography evidence of an occipital infarction. The association of migraine-like visual phenomena with cerebral venous thrombosis may provide insight into the pathogenesis of migraine.


Monitoring cooling water discharge using Lagrangian coherent structures: a case study in Daya Bay, China.
As an unwanted by-product in the power plants, cooling water (CW) discharge may induce harmful effects on the coastal environment. In this paper, to accurately predict the CW transport in the Daya Bay, China, we develop a three-dimensional hydrodynamic and temperature model to simulate the transport of the CW from nuclear power plant into coastal waters. Specifically, we use the flow velocity produced by the model to locate Lagrangian coherent structures (LCSs) hidden in ocean surface currents. Result show that the transport of the CW is quite strongly tied to the simulated LCSs. The LCSs constitute fluid barriers that accurately demarcate potential pathway for CW transport. Thus, LCSs in velocity fields from a coastal model is an extremely useful way to monitor and interpret the transport of CW.


Design, synthesis and molecular modeling study of acylated 1,2,4-triazole-3-acetates with potential anti-inflammatory activity.
The present investigation is concerned with the synthesis of different acylated 1,2,4-triazole-3-acetates with the objective of discovering novel and potent anti-inflammatory agents. Structures of the synthesized compounds were elucidated by spectral and elemental analyses. The obtained compounds were evaluated for their anti-inflammatory activites as well as gastric ulcerogenic effects and acute toxicity. Results showed that 1-acylated-5-amino-1,2,4-triazole-3-acetates 3a-e showed higher anti-inflammatory activity than the corresponding 5-acylamino derivatives 4a-e in carageenan-induced rat paw edema test with low gastric ulcerogenicity compared with indomethacin. Furthermore, molecular modeling studies were performed in order to rationalize the obtained biological results.


Focus on loupes.
This article aims to introduce the reader to the use of magnification in clinical dentistry and describes the lens systems available. The main principles of dental loupes are discussed and some of the potential problems outlined in order to help clinicians choose a magnification suited to their needs, provide years of service, and reduce the risk of eye, neck and back strain. The additional benefits and disadvantages of adding supplementary illumination, and the options available, are also considered.


Gender differences in tumor characteristics, treatment and survival of colorectal cancer: A population-based study.
The importance of sex and gender as modifiers of health and disease is increasingly recognized. The aim of this study was to analyze gender differences in incidence, tumor characteristics, treatment and relative survival (RS) in colorectal cancer (CRC). Observational population-based study including patients diagnosed with CRC in the Netherlands between 2010 and 2020. Stratified by localization (colon/rectum) and age (18-55/56-70/≥71years), gender differences in incidence, tumor characteristics, treatment and RS were analyzed. Multivariable regression was used to analyze the influence of gender on treatment and RS. The age-standardized incidence per 100,000 person-years of colon and rectal cancer is higher among men than women (colon: 41.2 versus 32.4, rectum: 22.8 versus 12.6). Besides differences in patient- and tumor characteristics, differences in treatment allocation and RS were observed. Most strikingly, women aged ≥ 71 years with stage IV colon cancer are less often treated with systemic therapy (31.3 % versus 28.4 %, adjusted odds ratio (OR) 0.63, 95 % CI 0.48-0.83) and more often receive best supportive care only (47.6 % versus 40.0 %, adjusted OR 1.58, 95 % CI 1.19-2.11). Statistically significant and clinically relevant gender differences in incidence, patient- and tumor characteristics and treatment allocation are observed in patients with CRC. Reasons for differences in treatment allocation deserve further investigation.


Overdrainage phenomena in shunt treated hydrocephalus.
In addition to the high rate of shunt complications due to obstruction and infection there is a considerable number of undesirable side effects caused by excessive drainage of CSF. Four hundred shunt treated patients are analyzed for overdrainage signs: acute decompression symptoms produced by upward shifting of the brain stem, low pressure headaches (mostly transient), and microcephaly and head deformities like scaphocephaly in infants. Skull X-ray changes reflect adjustment to reduced intracranial content. Slit ventricles and a marked intolerance to minimal pressure rises may be quite troublesome. Subdural haematomas are only exceptionally space-occupying; in most instances they are space-filling. Causes, incidence, management, and prevention are discussed.


Atomic transient recorder.
In Bohr's model of the hydrogen atom, the electron takes about 150 attoseconds (1 as = 10(-18) s) to orbit around the proton, defining the characteristic timescale for dynamics in the electronic shell of atoms. Recording atomic transients in real time requires excitation and probing on this scale. The recent observation of single sub-femtosecond (1 fs = 10(-15) s) extreme ultraviolet (XUV) light pulses has stimulated the extension of techniques of femtochemistry into the attosecond regime. Here we demonstrate the generation and measurement of single 250-attosecond XUV pulses. We use these pulses to excite atoms, which in turn emit electrons. An intense, waveform-controlled, few cycle laser pulse obtains 'tomographic images' of the time-momentum distribution of the ejected electrons. Tomographic images of primary (photo)electrons yield accurate information of the duration and frequency sweep of the excitation pulse, whereas the same measurements on secondary (Auger) electrons will provide insight into the relaxation dynamics of the electronic shell following excitation. With the current approximately 750-nm laser probe and approximately 100-eV excitation, our transient recorder is capable of resolving atomic electron dynamics within the Bohr orbit time.


Modulation of MHC antigen expression by viruses and oncogenes.
It is becoming increasingly clear that regulation of MHC antigen expression by viruses and oncogenes, leading to either immune evasion or autoimmunity, is widespread and important in disease. At a recent meeting*, which brought together workers interested in tumour immunology, viral infection and the MHC, a number of mechanisms for the regulation of MHC antigen expression were revealed and the importance of balanced expression of MHC gene products to effective immunity was underlined.


The effect of quercetin on the pharmacokinetics of chlorzoxazone, a CYP2E1 substrate, in healthy subjects.
Previous in vitro studies have demonstrated that quercetin inhibits CYP2E1 enzyme, but there are no available data to indicate that quercetin inhibits CYP2E1 enzyme in humans. The purpose of the present study was to assess the effect of quercetin on CYP2E1 enzyme activity in healthy subjects using chlorzoxazone (CHZ) as a CYP2E1 substrate. An open-label, two-period, sequential study was conducted in 12 healthy subjects. A single dose of CHZ 250 mg was given to subjects during control phase and after treatment phases. Quercetin at a dose of 500 mg was given to subjects twice daily for a period of 10 days. The blood samples were collected at predetermined time intervals after CHZ dosing and analyzed to determine the concentrations of CHZ and 6-hydroxychlorzoxazone (6-OHCHZ). Treatment with quercetin significantly enhanced the maximum plasma concentration (C max), area under the curve (AUC), and half-life (t 1/2) by 47.8, 69.3, and 36.4%, respectively, while significantly decreased the elimination rate constant (k el) and apparent oral clearance (CL/F) of CHZ by 25.1 and 41.6%, respectively, in comparison with the control. On the other hand, C max and AUC of 6-OHCHZ were decreased by 30.1 and 32.6%, respectively, after quercetin treatment when compared to control. In addition, geometric mean ratios and 90% confidence intervals for C max and AUC of CHZ and 6-OHCHZ were both out of the no-effect boundaries of 0.80-1.25, which indicates a significant pharmacokinetic interaction present between CHZ and quercetin. Furthermore, treatment with quercetin significantly decreased the metabolic ratios of C max and AUC by 57.1 and 60.1%, respectively, as compared to control suggesting that reduced formation of CHZ to 6-OHCHZ. The results suggest that altered pharmacokinetics of CHZ might be attributed to quercetin-mediated inhibition of CYP2E1 enzyme. Further, the inhibition of CYP2E1 by quercetin may represent a novel therapeutic approach for minimizing the ethanol-induced CYP2E1 enzyme activity and results in reduced hepatotoxicity of ethanol.


[Motoric cognitive risk syndrome-Setting the course for dementia prevention?]
The predicted increase in adults with dementia will pose a major challenge for the German healthcare system. To mitigate this challenge, the early detection of adults with an increased risk of dementia is crucial. In this context, the concept of motoric cognitive risk (MCR) syndrome has been introduced into the English literature but is currently relatively unknown in German-speaking countries. What are the characteristics and diagnostic criteria of MCR? What is the impact of MCR on health-related parameters? What is the current state of evidence regarding the risk factors and prevention of the MCR? We reviewed the English language literature concerning MCR, the associated risk factors, and protective factors, similarities or differences with the concept of mild cognitive impairment (MCI), and its influence on the central nervous system. The MCR syndrome is characterized by subjective cognitive impairment and a slower gait speed. Compared to healthy adults, adults with the MCR have a higher risk of dementia, falls, and mortality. Modifiable risk factors provide a starting point for specific multimodal lifestyle-related preventive interventions. As MCR can be easily diagnosed in practical settings, it could become an important concept for the early detection of adults with an increased risk of dementia in German-speaking countries, although further research is necessary to empirically confirm this assumption.


Parameters and sites of brainstem stimulation capable of eliciting the rabbit nictitating membrane response.
One hundred and thirty-five different combinations of pulse amplitude, pulse width, pulse train duration, and pulse frequency were delivered to either pars oralis of the spinal trigeminal nucleus, the accessory abducens nucleus, the abducens nucleus, or the reticular formation at the level of the spinal trigeminal nucleus. The percentage of occurrence, amplitude, and latency of the rabbit nictitating membrane response were shown to be lawfully related to the parameters of stimulation. Moreover, the electrode sites were ordered from reticular formation to abducens to accessory abducens to pars oralis in terms of the increasing efficacy with which stimulation elicited the nictitating membrane response.


Evaluating response to mood stabilizers in patients with mixed depression: A study of agreement between three different mania rating scales and a depression rating scale.
The aim of the present study was to evaluate agreement between three pairs formed by one of three mania scales (Young Mania Rating Scale [YMRS], Bech-Rafaelsen Mania Scale [BRMS], or the Clinician-Administered Rating Scale for Mania [CARS-M]) and a single depression scale (21-item Hamilton Depression Rating Scale [21-HAM-D]) for evaluation of response to mood stabilizers in patients with mixed bipolar disorder. Between 2010 and 2014, 68 consecutive bipolar type I and II outpatients with mixed depression as per DSM-IV-TR and Cincinnati criteria were included in this 8-week open-label trial to randomly receive carbamazepine, lithium carbonate, or valproic acid as monotherapy. Patterns of response (defined as a reduction of at least 50% in one of the mania scales and on the 21-HAM-D) were strikingly similar: 21-HAM-D+YMRS=22.1%, 21-HAM-D+BRMS=20.6%, and 21-HAM-D+CARS-M=23.5% (p<0.368). Assessment of agreement revealed very high kappa coefficients: 21-HAM-D+YMRS vs. 21-HAM-D+CARS-M, kappa=0.87; 21-HAM-D+YMRS vs. 21-HAM-D+BRMS, kappa=0.78; 21-HAM-D+CARS-M vs. 21-HAM-D+BRMS, kappa=0.91 (p<0.001). The decision to combine a depression rating scale with any one mania rating scale to assess treatment response in patients with mixed depression is questionable. The present study suggests that any one of the three tested mania rating scales (YMRS, BRMS, and CARS-M) can be combined with the 21-HAM-D to assess treatment response in patients with mixed bipolar disorder. This should give clinicians an added measure of confidence in using this strategy until valid, and specific instruments are developed for assessment of mixed states.


Incidence and mortality of hospital- and ICU-treated sepsis: results from an updated and expanded systematic review and meta-analysis.
To investigate the global burden of sepsis in hospitalized adults by updating and expanding a systematic review and meta-analysis and to compare findings with recent Institute for Health Metrics and Evaluation (IHME) sepsis estimates. Thirteen electronic databases were searched for studies on population-level sepsis incidence defined according to clinical criteria (Sepsis-1, -2: severe sepsis criteria, or sepsis-3: sepsis criteria) or relevant ICD-codes. The search of the original systematic review was updated for studies published 05/2015-02/2019 and complemented by a search targeting low- or middle-income-country (LMIC) studies published 01/1979-02/2019. We performed a random-effects meta-analysis with incidence of hospital- and ICU-treated sepsis and proportion of deaths among these sepsis cases as outcomes. Of 4746 results, 28 met the inclusion criteria. 21 studies contributed data for the meta-analysis and were pooled with 30 studies from the original meta-analysis. Pooled incidence was 189 [95% CI 133, 267] hospital-treated sepsis cases per 100,000 person-years. An estimated 26.7% [22.9, 30.7] of sepsis patients died. Estimated incidence of ICU-treated sepsis was 58 [42, 81] per 100,000 person-years, of which 41.9% [95% CI 36.2, 47.7] died prior to hospital discharge. There was a considerably higher incidence of hospital-treated sepsis observed after 2008 (+ 46% compared to the overall time frame). Compared to results from the IHME study, we found an approximately 50% lower incidence of hospital-treated sepsis. The majority of studies included were based on administrative data, thus limiting our ability to assess temporal trends and regional differences. The incidence of sepsis remains unknown for the vast majority of LMICs, highlighting the urgent need for improved epidemiological sepsis surveillance.


Left atrial primary B cell lymphoma presenting with mitral regurgitation.
Primary cardiac lymphoma (PCL) is an extremely rare diagnosis. We present a case of a 38-year-old immunocompetent female who presented with dyspnea on exertion and chest pain and the echocardiography revealed a mass in the left atrium (LA) causing moderate mitral regurgitation and mimicking a left atrial myxoma. The patient was managed with excision of the mass and mitral valve replacement followed by chemotherapy. The histopathology revealed B-cell non-Hodgkin lymphoma (NHL) with tumor cells showing immunoreactivity with CD20 and negative for CD45RO.


Cuticular hydrocarbons of buffalo fly, Haematobia exigua, and chemotaxonomic differentiation from horn fly, H. irritans.
We determined the quantity and chemical composition of cuticular hydrocarbons of different strains, sexes, and ages of buffalo flies, Haematobia exigua. The quantity of cuticular hydrocarbons increased from less than 1 microg/fly for newly emerged flies to over 11 microg/fly in 13-d-old flies. The hydrocarbon chain length varied from C(21) to C(29), with unbranched alkanes and monounsaturated alkenes the major components. Newly emerged flies contained almost exclusively C(27) hydrocarbons. Increasing age was accompanied by the appearance of hydrocarbons with shorter carbon chains and an increase in the proportion of alkenes. 11-Tricosene and 7-tricosene were the most abundant hydrocarbons in mature H. exigua. Cuticular hydrocarbons of H. exigua are distinctly different from those of horn flies, Haematobia irritans. The most noticeable differences were in the C(23) alkenes, with the major isomers 11- and 7-tricosene in H. exigua and (Z)-9- and (Z)-5-tricosene in H. irritans, respectively. Cuticular hydrocarbon analysis provides a reliable method to differentiate the two species, which are morphologically difficult to separate. The differences in cuticular hydrocarbons also support their recognition as separate species, H. exigua and H. irritans, rather than as subspecies.


Common genes regulate food and ethanol intake in Drosophila.
The abuse liability of alcohol (ethanol) is believed to result in part from its actions on neurobiological substrates that underlie the motivation toward food and other natural reinforcers, and a growing body of evidence indicates that these substrates are broadly conserved among animal phyla. Understanding the extent to which the substrates regulating ethanol and food intake overlap is an important step toward developing therapeutics that selectively reduce ethanol intake. In the current experiments, we measured food and ethanol intake in Recombinant Inbred (RI) lines of Drosophila melanogaster using several assays, and then calculated genetic correlations to estimate the degree to which common genes might underlie behavior in these assays. We found that food intake and ethanol intake as measured in the capillary assay are genetically correlated traits in D. melanogaster, as well as in a panel of 11 Drosophila species that we tested subsequently. RI line differences in food intake in a dyed food assay were genetically unrelated to ethanol intake in the capillary assay or to ethanol preference measured using an olfactory trap apparatus. Using publicly available gene expression data, we found that expression profiles across the RI lines of a number of genes (including the D2-like dopamine receptor, DOPA decarboxylase, and fruitless) correlated with the RI line differences in food and ethanol intake we measured, while the expression profiles of other genes, including NPF, and the NPF and 5-HT2 receptors, correlated only with ethanol intake or preference. Our results suggest that food and ethanol intake are regulated by some common genes in Drosophila, but that other genes regulate ethanol intake independently of food intake. These results have implications toward the development of therapeutics that preferentially reduce ethanol intake.


Cognitive profiles of three clusters of patients with a first-episode psychosis.
The primary objective was to identify specific groups of patients with a first-episode psychosis based on family history, obstetric complications, neurological soft signs, and premorbid functioning. The secondary objective was to relate these groups with cognitive variables. A total of 62 first-episode psychoses were recruited from adult and child and adolescent mental health services. The inclusion criteria were patients between 7 and 65 years old (real range of the samples was 13-35 years old), two or more psychotic symptoms and less than one year from the onset of the symptoms. Premorbid functioning (PAS), soft signs (NES), obstetric complications and a neuropsychological battery (CPT, TMTA/TMTB, TAVEC/TAVECI, Stroop, specific subtest of WAIS-III/WISC-IV) were administered. We found three clusters: 1) higher neurodevelopment contribution (N=14), 2) higher genetic contribution (N=30), and 3) lower neurodevelopment contribution (N=18). Statistical differences were found between groups in TMTB, learning curve of the TAVEC, digits of the WAIS and premorbid estimated IQ, the cluster 1 being the most impaired. A cluster approach could differentiate several groups of patients with different cognitive performance. Neuropsychological interventions, as cognitive remediation, should be addressed specifically to patients with more impaired results.


Characterization of an hospital disseminated plasmid encoding resistance to gentamicin and other antimicrobial agents.
A preliminary report has shown the existence of an endemic R plasmid in the University Hospital of Zaragoza. The results presented in this paper demonstrate the dissemination of a new 73 kilobases plasmid into multiple strains and species of gram-negative bacilli. This transferable plasmid belongs to Incompatibility group P and mediates resistance to ampicillin, tetracycline, gentamicin, kanamycin, streptomycin, chloramphenicol and sulfamethoxazole, synthesizing the aminoglycoside-modifying enzymes 3-acetyltransferase, 3'phosphotransferase, and 3"nucleotidyltransferase, and a TEM-1 beta-lactamase. These results and the previous findings show that a family of gentamicin-resistance plasmids exists among the gram-negative bacteria in the University Hospital. Resistance to gentamicin in all these plasmids is associated with the formation of 3-N-acetyltransferases.


Cloning and expression of IspDF from Mesorhizobium loti. Characterization of a bifunctional protein that catalyzes non-consecutive steps in the methylerythritol phosphate pathway.
Gram-negative bacteria, plant chloroplasts, green algae and some Gram-positive bacteria utilize the 2-C-methyl-d-erythritol phosphate (MEP) pathway for the biosynthesis of isoprenoids. IspD, ispE, and ispF encode the enzymes required to convert MEP to 2-C-methyl-d-erythritol 2,4-cyclodiphosphate (cMEDP) during the biosynthesis of isopentenyl diphosphate and dimethylallyl diphosphate in the MEP pathway. Upon analysis of the Mesorhizobium loti genome, ORF mll0395 showed homology to both ispD and ispF and appeared to encode a fusion protein. M. loti ispE was located elsewhere on the chromosome. Purified recombinant IspDF protein was mostly a homodimer, MW approximately 46 kDa/subunit. Incubation of IspDF with MEP, CTP, and ATP gave 4-diphosphocytidyl-2-C-methyl-d-erythritol (CDP-ME) as the only product. When Escherichia coli IspE protein was added to the incubation mixture, cMEDP was formed. In addition, M. loti ORF mll0395 complements lethal disruptions in both ispD and ispF in Salmonella typhimurium. These results indicate that IspDF is a bifunctional protein, which catalyzes the first and third steps in the conversion of MEP to cMEDP.


Spinal arteriovenous malformations and fistulae: clinical, neuroradiological and neurophysiological findings.
Twenty-six patients with myelographic signs suggestive of a spinal arteriovenous malformation (AVM) were examined neurologically and neurophysiologically. By selective spinal angiography it was possible to differentiate between dural arteriovenous fistulae (dAVF 20 patients) and intradural AVMs (iAVM, 6 patients). Initial complaints were nonspecific and variable, mainly consisting of sensory disorders and muscle weakness. Later, patients suffered involvement of both the upper and lower motor neurons. There was a high percentage of lower motor neuron lesions (95%), especially in dAVF patients, which were mostly of widespread distribution and included several myotomes. Electrophysiological examination regularly revealed lower neuron involvement, frequently with pathological spontaneous activity in several myotomes, pathological sensory-evoked potentials after tibial nerve stimulation, but normal sensory conduction velocities of the sural nerve, indicating sparing of the sensory ganglion. Frequently there was a discrepancy between the localization of the dural fistula or angioma and the spinal level responsible for clinical symptoms. This suggests that it may be the inadequacy of the venous drainage system to cope with the blood volume rather than the AV-shunt that is responsible for the symptoms. An early diagnosis is essential, as removal of the shunt before there has been progression to severe neurological deficits (paraplegia) is the only way to ensure a satisfactory outcome.


Ni(II), Cr(VI), Cu(II) and nitrate removal by the co-system of Pseudomonas hibiscicola strain L1 immobilized on peanut shell biochar.
At present, the improvement of nitrate and mixed heavy metals removal in wastewater by microorganism are urgently needed. Previous studies have shown that Pseudomonas hibiscicola strain L1 exhibited Ni(II) removal ability under aerobic denitrification. In this study, the characteristics of the free strain L1, peanut shell biochar (PBC) and further the co-system of strain L1 immobilized on PBC were investigated for the removal of Ni(II), Cr(VI), Cu(II) and nitrate in mix-wastewater. The results illustrated that strain L1 could remove 15.51% - 32.55% of Ni(II) (20-100 mg·L-1), and removal ratios by co-system were ranked as Ni(II) (81.17%) > Cu(II) (45.84%) > Cr(VI) (38.21%). Scanning Electron Microscope (SEM), X-ray Diffractometer (XRD) and Fourier Transform Infrared Spectroscopy (FTIR) images indicated that the strain L1 immobilized well on PBC and had vigorous biological activity; the crystals of Ni(OH)2, Cu(OH)2 and CrO(OH) etc. were formed on surface of co-system with various functional groups participated in. In Sequential Batch Reactor (SBR), the pollutant removal ratios by co-system were higher than that by free strain L1. This study illustrated that the co-system of strain L1 immobilized on PBC was qualified to be applied for practical scenarios of effective heavy metal removal of electroplating mix-wastewater.


Integrins in human cells and tumors.
We have studied the distribution of the alpha- and beta-subunits of integrins in developing and adult human kidney as well as in selected other tissues and cultured cells. In cultured cells some of the integrin subunits (beta 1, alpha 1, alpha 2 and alpha 5) colocalize with talin at focal adhesions when plated on an appropriate ligand. Similarly, in tissues the polarization of beta 1-integrins in colocalization with talin appears to indicate adhesive complexes, as demonstrated in adult glomeruli. In human kidney, the alpha subunits of integrins were seen to be segment-specifically expressed already in fetal tissues. In glomeruli the integrin alpha 1 subunit characterized mesangial cells while the alpha 2 and alpha 3 subunits showed immunoreactivity in endothelial cells and podocytes, respectively. In renal tubuli, the alpha 6 subunit, complexed with the beta 1 subunit, showed a typical polarized distribution coaligning with the tubular basement membrane while the alpha 3 and alpha 2 subunits were expressed in distal tubular cells. These results suggested that in kidney the alpha 2 beta 1, alpha 3 beta 1, and alpha 6 beta 1 integrins can function as basement membrane receptors. The alpha 5 subunit was nearly lacking in the kidney and it appears to be mainly expressed in some smooth muscle cells. In other tissues distinct patterns in the expression of integrins were found. Thus, in many glandular epithelial cells the alpha 3 beta 1 integrin appeared to function as a basement membrane receptor while in various stratified epithelia and in the breast such a polarized localization could be found for the alpha 6 beta 4 integrin. Finally, although presenting a clearly polarized distribution for beta 1 integrins, none of the alpha subunits could be found in cardiac or skeletal muscle cells and none of the integrins could be revealed in neuronal cells of human developing and adult cerebrum or cerebellum, although neurons in peripheral tissues contained abundantly the alpha 6 beta 1 integrin complex. In human tumors, the tumor cells, including also metastastatic tumors, generally presented the same integrins as their tissues of origin. In some poorly differentiated tumors both a population heterogeneity and even a lack of expression or a disorganization of basement membrane receptor integrins was obvious.


Isolation and characterization of poly(adenylic acid)-containing messenger ribonucleic acid from rat liver polysomes.
Undegraded rat liver polysomes were obtained after homogenizing the tissue in a medium containing NH4Cl, heparine, and yeast tRNA. Purification of poly(A)-containing RNA from polysomal RNA was accomplished by affinity chromatography on oligo(dT)-cellulose columns. Poly(A)-containing RNA molecules were monitored by the formation of ribonuclease-resistant hybrids with [3H]poly(U). To improve the separation of messenger RNA and ribosomal RNA by oligo(dT)-cellulose it was found essential to dissociate the aggregates formed between both molecular species by heat treatment in the presence of dimethylsulfoxide (Me2SO) prior to chromatography. Sucrose gradient analysis under denaturing conditions showed that the preparations obtained were virtually free of ribosomal RNA. Poly(A)-containing RNA constituted approx. 2.2% of the total polysomal RNA and the number average size was 1500--1800 nucleotides, as judged by sedimentation analysis on sucrose density gradients containing Me2SO. Approximately 8.2% of the purified preparation obtained was able to anneal with [3H]poly(U); the number average nucleotide length of the poly(A) segment of the RNA population was calculated to be 133 adenylate residues. Based on these values, our preparations appear to be greater than 90% pure. The RNA fractions obtained after oligo(dT)-cellulose chromatography were used to direct the synthesis of liver polypeptides in a heterologous cell-free system derived from wheat-germ. The system was optimized with respect to monovalent and divalent cations, and presence of polyamines (spermine). More than 65% of the translational activity present in the unfractionated polysomal RNA was recovered in the final poly(A)-containing RNA fraction. However, about 25% of the activity was found to be associated with the unbound fraction which was essentially free of poly(A)-containing RNA. Immunoprecipitation analysis with a specific antiserum to rat serum albumin demonstrated that about 6--8% of the labeled synthetic products translated from the poly(A)-containing RNA sample corresponded to serum albumin. Analysis of the translation products by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed a heterogeneous distribution of molecular sizes ranging from 15 000 to greater than 70 000 daltons. Spermine not only increased the overall yield and extent of protein synthesis, but also resulted in higher yields of large protein products. Under optimal translation conditions a discrete peak representing about 7% of the total radioactivity was observed to migrate with rat serum albumin.


Primary epithelioid sarcoma of the neck: a rare case report.
This report presents a case of a neck epithelioid sarcoma in a 20-year-old man with poor prognosis. The patient underwent surgery followed by external beam radiotherapy and brachytherapy performed as a boost. The treatment was well-tolerated, and there was no local recurrence or distant metastasis.


Emotional Intelligence from Gender Perspective during Mid to Late Adolescence in an Indian Context.
Emotional Intelligence (EI) contributes to overall success in life. Our objectives are to explore EI among adolescents and its gender differences as per some parameters of social environments. Present cross-sectional study was conducted in secondary schools in one of municipal corporations in western Maharashtra EI of adolescents studying in tenth standard in randomly selected secondary schools, was assessed by Schutte's Self-Reported Emotional Intelligence Test with collection of relevant sociodemographic information maintaining confidentiality. Data were analyzed by SPSS 20 software. Total 1060 adolescents in 14-16 years of age participated in the study. Socio-economic status affected EI of adolescent girls more adversely than adolescent boys (P = 0.003, P = 0.036 respectively). Co-educational type of school favored lower EI than gender specific schools (P < 0.001). After gender wise stratification, EI did not differ significantly among boys (P = 0.154) with respect to type of schooling, but differed significantly (P = 0.001) among girls. Apart from continued efforts directed to for improvement in SES, mental health component of school health services needs to take a step forward for assessment and improvement of towards mental health parameters including EI of adolescents. EI training programs commenced in school activities based on gender, socio-economic status and other issues relevant to the situation shall prove beneficial in long run.


Anaplastic large cell lymphoma in a patient with MAGIC syndrome: a case and review of the literature.
Mouth and genital ulcer with inflamed cartilage syndrome (MAGIC syndrome) is a rare autoinflammatory disorder with unknown etiology. Except for the common clinical manifestations mimicking Behçet's disease and relapsing polychondritis, some other clinical entities are occasionally observed. In this report, we present a case in which a patient developed anaplastic large cell lymphoma 1 year after the diagnosis of MAGIC syndrome. Additionally, we review the clinical manifestations, management, and prognosis of MAGIC syndrome.


EpCAM aptamer activated 5-FU-loaded PLGA nanoparticles in CRC treatment; in vitro and in vivo study.
In this study, epithelial cell adhesion molecule (EpCAM) aptamer-activated nanoparticles (Ap-NPs) were synthesised to enhance treatment efficiency in colorectal cancer (CRC). PLGA [poly(d, l-lactide-co-glycolide)] copolymer was fabricated by conjugation of COOH-PEG-NH2 to PLGA-COOH through an EDC/NHS-mediated chemistry. Afterwards, 5-fluorouracil-loaded (FU) nanoparticles were prepared using the water/oil/water double emulsion solvent evaporation method. The in vitro cytotoxicity of formulations was evaluated using the MTT assay in HCT-116, CT-26 and HEK-293 cell lines. For in vivo study, tumour-bearing BALB/c mice were established by subcutaneous injection of CT-26 cell line. The results indicated that fabricated AP-FU-NPs had 101 nm size with a spherical surface, relatively homogeneously and, satisfactory encapsulation efficiency (83.93%). In vitro experiments revealed that Ap-FU-NPs had a superior in vitro cytotoxicity than both FU-NPs and free 5-FU in CT-26 and HCT-116 cells but, were significantly low toxic against HEK-293 cells relative to free 5-FU. Furthermore, in vivo results showed no significant haemolytic effect, hepatic and renal injury, or weight loss. After treatment of various animal groups with formulations, notable tumour growth delay was observed following the order: Ap-FU-NPs < FU-NPs < 5-FU < PBS. The results suggest that AP-FU-NPs could be an effective and promising carrier for 5-FU delivery to the EpCAM overexpressing CRC cells.


The effect of submaximal exercise on immuno- and bioassayable IGF-I activity in patients with GH-deficiency and healthy subjects.
Growth hormone (GH) increases during exercise, but the response of the insulin-like growth factor (IGF) system has not been as definitive. Therefore, we investigated the effect of the exercise-induced GH response on the circulating IGF-system in GH-deficient (GHD) and intact adults. Eight GHD adults were studied on 2 occasions, with (+GH) and without (-GH) GH administered (0.4 IU) during exercise (45 min of cycle ergometer exercise at the lactate threshold). Eight age-matched controls were only studied on one occasion. Blood samples were drawn at baseline, during and post-exercise. IGFBP-3 proteolysis was measured by an in vitro proteolytic activity assay, IGF-I bioactivity by novel IGF-I kinase receptor activation assay (KIRA) and other hormones by immunoassay. GH administration to GHD adults resulted in a serum GH peak similar to the exercise-stimulated GH response in GH intact controls, but exercise had only a small impact on the IGF system. IGF-I concentration was lower in controls but was only significantly lower than the +GH day. Neither IGF-I nor -II levels changed over time. IGFBP-1 demonstrated a time effect (P<0.01) in all groups, and a time x group interaction (P<0.01) with a rise at 75 min post-exercise, which was greater in the GHD subjects than controls. IGFBP-2 and -3 increased significantly (P<0.01) over time in the GHD subjects, but not in the controls. No change in IGFBP-3 proteolysis or IGF-I bioactivity was found during exercise or recovery in either group. Submaximal exercise induced minor changes in IGFBP-1, -2 and -3, without affecting IGFBP-3 proteolysis and IGF-I bioavailability. Thus the metabolic status during submaximal exercise does not require a change in plasma IGF-I bioavailability. Administration of GH to GHD adults does not result in changes in proteolysis or bioavailability.


Phosphate: the new cholesterol? The role of the phosphate axis in non-uremic vascular disease.
Higher serum phosphate levels within the normal range are associated with substantially increased risk of cardiovascular disease events. Whether this reflects a causative relationship is unknown. Phosphate-responsive hormones (fibroblast growth factor-23, parathyroid hormone and calcitriol) are also predictors of cardiovascular mortality in populations without kidney disease or recognised disturbances of bone mineral metabolism. The high bioavailable phosphate content of Western diets may contribute to this apparent discrepancy between 'normal' and optimal phosphate axis parameters. Although uremic hyperphosphatemia is recognised to cause vascular medial calcification, this does not readily explain the association of higher-normal phosphate with common athero-occlusive phenomena. The phosphate axis may in fact play a role in atherogenesis; observational data link higher levels of phosphate and fibroblast growth factor-23 with coronary atheroma burden, whilst dietary phosphate supplementation accelerates atherosclerosis in a mouse model. In vitro studies show adverse effects of phosphate increases on both vascular smooth muscle cells and endothelium, though these observations have not yet been extended to phosphate increments within the normal range. Receptors for phosphate-responsive hormones are present throughout the cardiovascular system and may mediate atherogenic effects. Since interventions are already available to manipulate the phosphate axis, this is an important issue. If an atherogenic role for phosphate exposure is demonstrated then phosphate binders could become the new statins.


Interrelationship between drug oxidation ureogenesis and gluconeogenesis in isolated hepatocytes.
1. The effect of increased ureogenesis--provoked by NH4Cl and ornithine--on gluconeogenesis and aminopyrine oxidation was studied in isolated hepatocytes prepared from 24 hr starved mice; lactate or fructose was used as gluconeogenic precursor. 2. Increased ureogenesis caused about 40% inhibition both on aminopyrine oxidation and gluconeogenesis when lactate was added as gluconeogenic substrate. 3. On the other hand, only 10% inhibition of aminopyrine oxidation and about 15% inhibition of gluconeogenesis were observed when fructose was used as gluconeogenic precursor. 4. Aminopyrine has been reported to inhibit gluconeogenesis from fructose by 30% and from lactate by 85%. The inhibitory effect of the combined addition of aminopyrine, NH4Cl and ornithine on gluconeogenesis was also dependent on the applied gluconeogenic precursor. 5. The provoked ureogenesis by ammonia and ornithine was not inhibited by aminopyrine. N6, O2-dibutyryl cAMP known to cause an increase of gluconeogenesis a decrease of aminopyrine oxidation enhanced the inhibitory action of increased ureogenesis on aminopyrine oxidation and on gluconeogenesis further. 6. The role of NADPH in the regulation of drug oxidation and ureogenesis is underlined.


Distinct pattern of matrix metalloproteinase 9 and tissue inhibitor of metalloproteinase 1 mRNA expression in human colorectal cancer and liver metastases.
The matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are perceived as essential for tumour invasion and metastasis. In the present study, we compare the topographical pattern of MMP-9 and TIMP-1 expression in colorectal cancer and liver metastasis by in situ hybridisation. TIMP-1 mRNA was detected in all 26 colorectal cancers examined, while only 18 out of 26 (69.2%) were positive for MMP-9. Both MMP-9 and TIMP-1 mRNA were observed in all ten liver metastases but were absent in three adenomas and in all normal colonic mucosa and liver. There was no association between MMP-9 or TIMP-1 mRNA expression and degree of differentiation or size of Tumours. MMP-9 and TIMP-1 mRNA were similarly observed in the peritumour stroma cells rather than in tumour cells themselves. MMP-9 mRNA positive cells were round and identified as macrophages by immunostaining with an anti-macrophage antibody (KP1), while TIMP-1, mRNA was detected in spindle-shaped stromal cells. In liver metastases, MMP-9 localised within peritumour stroma or at the interface between the tumour stroma and normal liver, whereas TIMP-1 mRNA was located throughout the malignant tumour stroma. Our data demonstrate a distinct pattern of MMP-9 and TIMP-1 mRNA expression in colorectal cancer and liver metastases suggesting distinct cellular origins as well as separate patterns of regulation.


[Roles and Work Content of Peer Workers and Experts by Experience in Mental Health Practice, Education, Research and Development - Results of a Survey in Switzerland].
To identify work contents, roles and tasks of peer workers in mental health services in the German-speaking part of Switzerland. A survey was conducted among peers in the German-speaking part of Switzerland. Most respondents stated that they work mainly in specialized services in the treatment of people with psychoses and affective disorders and in direct contact with service users. "Building bridges" between service users and professionals, conveying hope and confidence, empowerment as well as support in symptom management was most frequently indicated as a work activity. The majority of respondents have job descriptions that correspond to their activities. For mental health services, the challenge is to integrate the new professional group of peers workers as well as possible without undermining their proximity to the service users or their possibly critical perspective with regard to the existing practice.


Role of reverse transcription in the generation of extrachromosomal copia mobile genetic elements.
The Drosophila genetic element copia is one of the best studied eukaryotic transposable sequences. Copia shares structural features with a wide variety of mobile elements in Drosophila, Lepidoptera, yeast and vertebrates, the last class being the retrovirus proviruses. Furthermore, retrovirus-like particles containing copia RNA have been isolated from Drosophila cells and extrachromosomal circular copias with structures closely resembling circular retrovirus proviruses have been isolated and cloned. Therefore, copia-like elements and retroviruses may be members of a class of mobile genetic elements existing throughout the eukaryotic kingdom. Consequently, there has been speculation that retroviruses evolved from transposable elements and, conversely, that copia-like elements transpose as retroviruses or retrovirus-like particles. To date, however, there has been no demonstration that copia RNA is reverse transcribed into copia DNA. The present report describes the isolation of linear extrachromosomal copias whose structure closely resembles the analogous retrovirus provirus linears and whose synthesis is unaffected by inhibitors of the cellular DNA polymerase responsible for chromosomal DNA replication.


Establishing Chromatin Regulatory Landscape during Mouse Preimplantation Development.
How the chromatin regulatory landscape in the inner cell mass cells is established from differentially packaged sperm and egg genomes during preimplantation development is unknown. Here, we develop a low-input DNase I sequencing (liDNase-seq) method that allows us to generate maps of DNase I-hypersensitive site (DHS) of mouse preimplantation embryos from 1-cell to morula stage. The DHS landscape is progressively established with a drastic increase at the 8-cell stage. Paternal chromatin accessibility is quickly reprogrammed after fertilization to the level similar to maternal chromatin, while imprinted genes exhibit allelic accessibility bias. We demonstrate that transcription factor Nfya contributes to zygotic genome activation and DHS formation at the 2-cell stage and that Oct4 contributes to the DHSs gained at the 8-cell stage. Our study reveals the dynamic chromatin regulatory landscape during early development and identifies key transcription factors important for DHS establishment in mammalian embryos.


Effect of serum and serum components on the mitogen-induced proliferation of murine lymphocytes.
By increasing the concentration of human serum, the dose-response profile of the Concanavalin A-induced proliferation of murine spleen lymphocytes becomes broader and the optimal cell proliferation takes place at higher concentrations of mitogen. It is shown that this behavior is due to the globulin fraction of serum which greatly decreases the binding of Concanavalin A to lymphocytes. Cohn fractions III and IV have a similar effect. On the other hand, cell proliferation takes place also in the absence of Pooled Human Serum at appropriate concentrations of Concanavalin A and within a very narrow range of cell concentrations. In the presence of the albumin fraction of serum, proliferation takes place over a wider range of mitogen and cell concentrations. As a result of these phenomena, the mitogenic effect of Concanavalin A varies greatly in function of the concentration of serum. Analogous results were obtained with fetal calf serum.


Comparison of ornithine aminotransferase activities in the pigment epithelium and retina of vertebrates.
1. The specific activities of ornithine aminotransferase (OAT) in the pigment epithelia, retinas, and livers from several classes of vertebrates were assayed. 2. The specific activities of OAT were much higher in the pigment epithelia from mammals and birds than in their respective retinas or livers. 3. Pigment epithelium from porcine eyes had the highest specific activity measured. The specific activity of OAT in the pigment epithelium from the pig was five times higher than the OAT activity in its retina and 13 times higher than the OAT activity in its liver.


Positive and negative schizotypal symptoms relate to different aspects of crossover reaction time task performance.
Although the expressions of both positive and negative symptoms in schizophrenia spectrum illnesses can each occur with varying degrees of severity, researchers have often dichotomized patients as generally positive or negative subtypes. Studies of schizophrenia and schizotypal personality disorder (SPD) have not typically controlled for the severity of the other symptom types when examining the relationship between positive and negative symptom subtypes and cognitive impairment. The present study investigated the relationship between the severity of both symptom types and reaction time crossover task performance in SPD in groups made equivalent on the severity of the other type of symptom. Fifty-eight out of 458 undergraduates were screened into one of four groups (high negative-high positive, low negative-low positive, high negative-low positive or low negative-high positive) by the Schizotypal Personality Questionnaire and assessed with the reaction time crossover task. The results indicated that negative schizotypal symptoms were associated with the early crossover pattern, while positive schizotypal symptoms related to longer overall reaction time. Therefore, different cognitive mechanisms involved in crossover task performance appeared to be associated with different symptom subtypes.


Using Participatory Methods to Assess PrEP Interest and Uptake Among Young People Living in the Southeastern US: A Mixed Methods Assessment.
Adolescents and young adults (AYA; 13-24 years-old) comprise 22% of new HIV infections in the United States (US), most of whom live in the South. We used the situated-Information, Motivation, Behavioral skills (sIMB) model to identify priorities for intervention on multi-level factors that influence HIV preventive care among Black AYA in Durham, North Carolina. We conducted two participatory workshops (ages 13-17, N = 6; ages 18-24, N = 7) to engage youth about how to discuss HIV. We also assessed sIMB constructs from a separate quantitative sample of youth to contextualize the workshop findings (N = 80). HIV knowledge was low overall, but lower among younger Black AYA, suggesting a need for comprehensive sexual education. Trusted adults provided sexual health information, motivation for health maintenance, and behavioral skills support. HIV prevention interventions should provide comprehensive sexual health education to Black AYA, be age-specific, and include social supporters like parents, teachers, and community members.


Designing nursing interventions.
The development of nursing interventions that demonstrate the link between nursing actions and patient outcomes is a high priority for nursing research. The development of intervention research frequently focuses on the methods used to test the intervention while less attention is placed on rigor in intervention development and design. The purpose of this paper is to provide thinking points for researchers considering the development of nursing interventions. The thinking points were developed from the limited literature on this topic in synthesis with the authors own experiences of designing nursing interventions. Adoption of a systematic approach to intervention testing is advocated along with a step-wise intervention development process. This process calls for attention to problem definition, conceptual underpinnings, desired outcomes and measures and evidence-based content along with careful consideration of delivery methods, dose and attention to protecting the integrity of the intervention during testing. The approach advocated will help to ensure that nursing intervention research makes a useful contribution to the development of nursing practice.


Molecular structure of r(GCG)d(TATACGC): a DNA--RNA hybrid helix joined to double helical DNA.
The molecule r(GCG)d(TATACGC) is self-complementary and forms two DNA--RNA hybrid segments surrounding a central region of double helical DNA; its molecular structure has been solved by X-ray analysis. All three parts of the molecule adopt a conformation which is close to that seen in the 11-fold RNA double helix. The conformation of the ribonucleotides is partly determined by water molecules bridging between the ribose O2' hydroxyl group and cytosine O2. The hybrid-DNA duplex junction contains no structural discontinuities. However, the central DNA TATA sequence has some structural irregularities.


Cost-efficient improvement of coking wastewater biodegradability by multi-stages flow through peroxi-coagulation under low current load.
Cost-effective pretreatment of the highly concentrated and biorefractory coking wastewater to improve biodegradability is of significant importance, while green electrochemical technologies without external chemicals addition are charming but still challenging due to its high energy consumption. In this work, a novel multi-stages flow through peroxi-coagulation (PC) was for the first time developed with graphite felt cathode modified by graphene, showing an excellent performance in removal of 71.5% COD, 72.3% phenol and 59.4% NH3-N and significant biodegradability enhancement with a low energy consumption as 1.2 kWh/m3. Compared with conventional flow PC, this process was more cost-effective due to more intensive .OH production and higher utilization of generated active species. Through UV spectrophotometry and GC-MS analysis, the improvement of biodegradability was attributed to the reduction of both low and high molecular weight compounds content in the coking wastewater. Comparing to the electro-Fenton, electrocoagulation and ozonation process, the proposed PC process was highly cost-effective, providing a promising and new alternative for pretreatment of coking wastewater.


Progress in Bioinspired Dry and Wet Gradient Materials from Design Principles to Engineering Applications.
Nature does nothing in vain. Through millions of years of revolution, living organisms have evolved hierarchical and anisotropic structures to maximize their survival in complex and dynamic environments. Many of these structures are intrinsically heterogeneous and often with functional gradient distributions. Understanding the convergent and divergent gradient designs in the natural material systems may lead to a new paradigm shift in the development of next-generation high-performance bio-/nano-materials and devices that are critically needed in energy, environmental remediation, and biomedical fields. Herein, we review the basic design principles and highlight some of the prominent examples of gradient biological materials/structures discovered over the past few decades. Interestingly, despite the anisotropic features in one direction (i.e., in terms of gradient compositions and properties), these natural structures retain certain levels of symmetry, including point symmetry, axial symmetry, mirror symmetry, and 3D symmetry. We further demonstrate the state-of-the-art fabrication techniques and procedures in making the biomimetic counterparts. Some prototypes showcase optimized properties surpassing those seen in the biological model systems. Finally, we summarize the latest applications of these synthetic functional gradient materials and structures in robotics, biomedical, energy, and environmental fields, along with their future perspectives. This review may stimulate scientists, engineers, and inventors to explore this emerging and disruptive research methodology and endeavors.


Spatial-temporal trends in the risk of illicit drug toxicity death in British Columbia.
Illicit drug poisoning (overdose) continues to be an important public health problem with overdose-related deaths currently recorded at an unprecedented level. Understanding the geographic variations in fatal overdose mortality is necessary to avoid disproportionate risk resulting from service access inequity. We estimated the odds of fatal overdose per event from all cases captured by the overdose surveillance system in British Columbia (2015 - 2018), using both conventional logistic regression and Generalized Additive Models (GAM). The results of GAM were mapped to identify spatial-temporal trends in the risk of fatal overdose. We found that the odds of fatal overdose were about 30% higher in rural areas than in large urban centers, with some regions reporting odds 50% higher than others. Temporal variations in fatal overdose revealed an increasing trend over the entire province. However, the increase occurred earlier and faster in the Interior and Northern regions. Rural areas were disproportionately affected by fatal overdose; lack of access to harm reduction services may partly explain the elevated risk in these areas.


Recognition and management of pulmonary hypertension.
Pulmonary hypertension (mean pulmonary arterial pressure > 20mm Hg at rest or > 30mm Hg during exercise) occurs (i) as primary pulmonary hypertension (no known underlying cause), (ii) as persistent pulmonary hypertension of the newborn or (iii) secondary to a variety of lung and cardiovascular diseases. In the last 10 to 15 years there have been significant advances in the medical management of this debilitating and life-threatening disorder. The main drugs in current use are anticoagulants (warfarin, heparin) and vasodilators, especially oral calcium antagonists, intravenous prostacyclin (prostaglandin I2; epoprostenol) and inhaled nitric oxide. Calcium antagonists, (e.g. nifedipine, diltiazem) are used chiefly in primary pulmonary hypertension. They are effective in patients who give a pulmonary vasodilator response to an acute challenge with a short acting vasodilator (e.g. prostacyclin, nitric oxide or adenosine), and are used in doses greater than are usual in the treatment of other cardiovascular disorders. Prostacyclin, given by continuous intravenous infusion, is effective in patients even if they do not respond to an acute vasodilator challenge. The long term benefit in these patients is thought to reflect the antiproliferative effects of the drug and/or its ability to inhibit platelet aggregation. It is used either as long term therapy or as a bridge to transplantation. Inhaled nitric oxide, which is used mainly in persistent pulmonary hypertension of the newborn, has the particular benefit of being pulmonary selective, due to its route of administration and rapid inactivation. Anticoagulants have a specific role in the treatment of pulmonary thromboembolic pulmonary hypertension and are also used routinely in patients with primary pulmonary hypertension. Nondrug treatments for pulmonary hypertension include (i) supplemental oxygen (> or = 15 h/day), which is the primary therapy in patients with pulmonary hypertension secondary to chronic obstructive pulmonary disease and (ii) heart-lung or lung transplantation, which nowadays is regarded as a last resort. Different types of pulmonary hypertension require different treatment strategies. Future advances in the treatment of pulmonary hypertension may come from the use of drug combinations, the development of new drugs, such as endothelin antagonists, nitric oxide donors and potassium channel openers, or the application of gene therapy.


Engineering the AAV capsid to evade immune responses.
Gene therapy is progressively emerging as a promising and powerful therapeutic modality, and adeno-associated virus (AAV) is a major delivery vehicle for such therapies. Among the most significant challenges that limit AAV's utility, however, is the immune response it elicits. Antibodies elicited by prior exposure to natural virus or vector can bind to an AAV vector, preventing it from entering the cell. Furthermore, even if AAV manages to infect a target cell, these cells can then be attenuated by lymphocytes. Improvements in our understanding of how the immune system responds to AAV have guided engineering of the capsid to reduce those responses, yielding capsid variants that are much stealthier and more effective. This review summarizes recent advances in understanding the immune response to AAV as well as highlights engineering methods that enhance AAV's potential as a gene therapy vector.


Detection of Alcanivorax spp., Cycloclasticus spp., and Methanomicrobiales in water column and sediment samples in the Gulf of Mexico by qPCR.
Water column and sediment samples were collected in the southern Gulf of Mexico (GoMex) during 3 oceanographic cruises: XIXIMI-04 (September 2015), XIXIMI-05 (June 2016), and XIXIMI-06 (August 2017). DNA that was extracted from the samples was analyzed by qPCR to detect and quantify bacterial groups that have been reported to metabolize alkanes (Alcanivorax) and aromatic hydrocarbons (Cycloclasticus) and are involved in methane production (Methanomicrobiales). The results were then analyzed with regard to the water masses that are currently detected in the GoMex. Generally, we observed a decrease in the proportion of Alcanivorax and a rise in those of Cycloclasticus and Methanomicrobiales in samples from the surface to deep waters and in sediment samples. Scatterplots of the results showed that the relative abundance of the 3 groups was higher primarily from the surface to 1000 m, but the levels of Cycloclasticus and Methanomicrobiales were high in certain water samples below 1000 m and in sediments. In conclusion, oil-degrading bacteria are distributed widely from the surface to deep waters and sediments throughout the southern GoMex, representing a potential inoculum of bacteria for various hydrocarbon fractions that are ready for proliferation and degradation in the event of an oil spill from the seafloor or along the water column.


A long-term study of radiation therapy in t1-2 node-negative breast cancer patients in relation to the number of axillary nodes examined.
The optimal number of axillary nodes to be resected is controversial. This large series investigated the effect of surgery with or without adjuvant radiotherapy among node-negative breast cancer patients in relation to the number of nodes examined. Node-negative patients from the Saskatchewan registry of 1981-1995 were studied. Because nodal status may be more reliable with more number of nodes examined, we analyzed T1-2 age < 90 patients with < 10 nodes examined treated with surgery alone (Group A_S, n = 509) vs. surgery and adjuvant radiotherapy (Group A_S+R, n = 342); and T1-2 age < 90 patients with > or = 10 nodes examined treated with surgery alone (Group B_S, n = 902) vs. surgery and adjuvant radiotherapy (Group B_S+R, n = 596). For the two radiotherapy groups, patients with < 10 nodes (Group A_S+R) vs. > or = 10 nodes (Group B_S+R), there was no difference in overall survival (p = 0.14). In the two nonradiotherapy groups (A_S and B_S), there is a statistically significant decrease in overall survival for patients with < 10 nodes removed (p < 0.001, log-rank test). The optimal number of axillary nodes examined could be 8 nodes with adjuvant radiotherapy (p = 0.05, logrank test) and 12 nodes without adjuvant radiotherapy (p = 0.02, log-rank test). The poorer prognosis of a lesser number of nodes resected was overcome partly by the use of radiotherapy, raising the possibility of micrometastases in lymph nodes not removed. The optimal number of axillary nodes examined could be 8 nodes with adjuvant radiotherapy and 12 nodes without adjuvant radiotherapy.


[Extraoral accidents with endodontic rotary instruments. Report of two cases].
A serious warning against the possibility of extra-oral accidents caused by endodontic mechanically driven instruments is made. Some critical characteristics of such instruments are described, as well as physical, technical, ergonomic and human reasons conducting to these accidents, two cases of which are related. Finally, colleagues are invited to think critically upon their own rhythm of labour and some preventive measures are proposed.


Polarization-controllable Airy beams generated via a photoaligned director-variant liquid crystal mask.
Researches on Airy beams have grown explosively since the first demonstration in 2007 due to the distinguishing properties of nondiffraction, transverse acceleration and self-healing. To date, a simple and compact approach for generating Airy beams in high quality and efficiency has remained challenging. Here, we propose and demonstrate a liquid crystal (LC) polarization Airy mask (PAM) featured by spatially variant LC azimuthal director. The PAM is fabricated through photoaligning LC via a polarization-sensitive alignment agent suophonic azo dye SD1. Thanks to the special design, a novel feature of polarization-controllable switch between dual Airy beams of orthogonal circular polarization is presented. The molecular-level continuity of LC director significantly improves the quality and efficiency of resultant Airy beams. Besides, the PAM can handle intense light due to the absence of absorptive electrodes. Additional merits of compact size, low cost and broad wavelength tolerance are also exhibited. This work settles a fundamental requirement for Airy beam applications of optical manipulations, biology science and even some uncharted territories.


Electrical stimulation of the heart 7 acupuncture site for preventing emergence agitation in children: A randomised controlled trial.
Emergence agitation is common in children recovering from general anaesthesia. The prevention of emergence agitation remains an important challenge in the field of paediatric anaesthesia. We aimed to examine the effectiveness of electrically stimulating the heart 7 (HT7) acupuncture site with a peripheral nerve stimulator (PNS) during surgery, for preventing emergence agitation in paediatric patients recovering from general anaesthesia. A double-blind, randomised, controlled, parallel-group trial. Kanagawa Children's Medical Centre, Yokohama, Japan. One hundred and twenty patients aged 18 to 96 months (American Society of Anesthesiologists physical status I or II) undergoing minor elective surgery under general anaesthesia with sevoflurane. Patients were randomly assigned to either undergo bilateral stimulation of HT7 with two PNS devices (1 Hz, 50 mA) during surgery (Group HT7) or a control group that did not undergo electrical stimulation of HT7 during surgery. The primary outcome was the incidence of emergence agitation evaluated in the postanaesthesia care unit (PACU) using the Paediatric Anaesthesia Emergence Delirium scale. The secondary outcomes were the time from operation completion to tracheal extubation, PACU stay duration and postoperative pain scores. The incidence of emergence agitation was significantly lower in the HT7 group compared with the control group (31.7 vs. 56.7%, respectively; P = 0.010). The risk ratio was 0.56 (95% confidence interval 0.36 to 0.86) and the number needed to treat was 4 (95% confidence interval 3 to 13). There were no statistically significant differences between groups in time from operation completion to tracheal extubation, PACU stay duration or postoperative pain. Bilateral electrical stimulation of HT7 using two PNS devices significantly decreases the incidence of emergence agitation. UMIN Clinical Trial Registry (registry number: UMIN000011704).


Correlation between clinical and histological features in a pig model of choroidal neovascularization.
To analyse the histological changes in the retina and the choroid in a pig model of choroidal neovascularization (CNV) and to correlate these findings with fundus photographic and fluorescein angiographic features. CNV was induced by surgical removal of the retinal pigment epithelium (RPE) and perforation of Bruch's membrane in four pig eyes. In addition, two eyes had an amniotic membrane implanted in the subretinal space. Retinal landmarks such as arterioles, crossing of vessels and the optic nerve were used to obtain an exact mapping of histological findings on colour fundus photographs (FPs) and fluorescein angiograms (FAs). We analysed the appearance on the FPs and FAs of the following histological features: CNV, hypo/hyperpigmented RPE, and pathological changes to the retina and choroid. CNV was found in all eyes and correlated to areas with late staining but no leakage in the FAs. Areas of hypopigmented RPE were identified and corresponded to window defects in the FAs. Where fibrovascular tissue was covered with hyperpigmented RPE, blocked fluorescence was found on the FAs. The implanted amniotic membrane showed staining but no leakage in the FAs. In a pig model of surgically induced CNV, histological mapping was used to make clinicopathological correlations of the following lesion components: CNV, window defects, blocked fluorescence. Our findings give a more solid foundation for interpretation of fluorescein angiograms in pig models.


Gene deletion of Interleukin-1α reduces ER stress-induced CHOP expression in macrophages and attenuates the progression of atherosclerosis in apoE-deficient mice.
The pathophysiology of atherosclerosis initiation and progression involves many inflammatory cytokines, one of them is interleukin (IL)-1α that has been shown to be secreted by activated macrophages. We have previously shown that IL-1α from bone marrow-derived cells is critical for early atherosclerosis development in mice. It is known that endoplasmic reticulum (ER) stress in macrophages is involved in progression to more advanced atherosclerosis, but it is still unknown whether this effect is mediated through cytokine activation or secretion. We previously demonstrated that IL-1α is required in ER stress-induced activation of inflammatory cytokines in hepatocytes and in the associated induction of steatohepatitis. In the current study, we aimed to examine the potential role of IL-1α in ER stress-induced activation of macrophages, which is relevant to progression of atherosclerosis. First, we demonstrated that IL-1α is required for atherosclerosis development and progression in the apoE knockout (KO) mouse model of atherosclerosis. Next, we showed that ER stress in mouse macrophages results in the protein production and secretion of IL-1α in a dose-dependent manner, and that IL-1α is required in ER stress-induced production of the C/EBP homologous protein (CHOP), a critical step in ER stress-mediated apoptosis. We further demonstrated that IL-1α-dependent CHOP production in macrophages is specifically mediated through the PERK-ATF4 signaling pathway. Altogether, these findings highlight IL-1α as a potential target for prevention and treatment of atherosclerotic cardiovascular disease.


Measurements of half-life of rat cardiac myosin heavy chain with leucyl-tRNA used as precursor pool.
The kinetics of labeling of myosin heavy chain, following a single intravenous injection of L-[4,5-3H]leucine, were analyzed with the help of a computer, in conjunction with the labeling kinetics of the specific radioactivities of the precursor amino acid pool. As precursor we used leucyl-tRNA which, as we show here, differs significantly from the intracellular free leucine pool. The half-life of myosin heavy chain was determined from the initial period (0 to 60 min) of incorporation of label into protein after a single injection of tritiated leucine, and also from the period (7 to 14 days) when there is exponential decay of the labeled protein. Myosin heavy chain was separated from other myofibrillar proteins by polyacrylamide gel electrophoresis before measurement of leucine specific radioactivity. The specific radioactivity was measured in both protein and precursor pools by a sensitive isotope dilution procedure (range, 100 to 1500 pmol). The values for the half-life of myosin heavy chain determined at both intervals were similar (5.4 and 5.9 days). Substitution of the specific radioactivity of the intracellular free leucine pool decreased the half-life to 2.7 dyas. Similar values were obtained when the half-life was calculated by simple graphical integration of the experimental curves.


Laparoscopic upper pole partial nephrectomy with concomitant en bloc adrenalectomy.
To report our experience with laparoscopic partial nephrectomy for renal tumor with concomitant adrenalectomy. An upper pole renal tumor may contiguously involve the adrenal gland, requiring concomitant adrenalectomy. Although commonly performed in the setting of laparoscopic radical nephrectomy, concomitant adrenalectomy has not been described during laparoscopic partial nephrectomy. Four patients with an upper pole renal tumor and suspected adrenal involvement underwent laparoscopic partial nephrectomy with concomitant ipsilateral adrenalectomy. Preoperative three-dimensional computed tomography revealed the renal tumor to be closely abutting the adrenal gland in 3 patients and a 4-cm adrenal mass in 1 patient. The mean renal tumor size was 3.2 cm (range 1.4 to 6.6). To maintain oncologic principles, our transperitoneal laparoscopic technique excises the adrenal gland en bloc with the renal tumor. As such, adrenalectomy is performed first, followed by partial nephrectomy, incorporating hilar control, tumor excision, and sutured renal reconstruction. All four procedures were performed without open conversion or intraoperative complications. The mean renal warm ischemia time was 36 minutes, estimated blood loss 169 mL, total operating time 3.9 hours, and hospital stay 3.2 days. One patient developed a transient urinary leak postoperatively. Pathologic examination of the renal tumor revealed renal cell carcinoma (n = 1), dystrophic calcification with ectopic bone formation (n = 1), adult mesoblastic nephroma (n = 1), and subcapsular heterotopic adrenal cortex with cyst (n = 1), all with negative surgical margins. Pathologic examination of the adrenal gland revealed adenoma in 1 case and a normal adrenal gland without malignant involvement in 3 cases. All patients were disease free at last follow-up (mean 6.2 months, range 2 to 12). In patients with an upper pole renal tumor and radiologically suspected adrenal involvement, laparoscopic partial nephrectomy with concomitant adrenalectomy can be performed efficaciously respecting oncologic principles.


Twitter as an innovation process with damping effect.
In the existing literature about innovation processes, the proposed models often satisfy the Heaps' law, regarding the rate at which novelties appear, and the Zipf's law, that states a power law behavior for the frequency distribution of the elements. However, there are empirical cases far from showing a pure power law behavior and such a deviation is mostly present for elements with high frequencies. We explain this phenomenon by means of a suitable "damping" effect in the probability of a repetition of an old element. We introduce an extremely general model, whose key element is the update function, that can be suitably chosen in order to reproduce the behaviour exhibited by the empirical data. In particular, we explicit the update function for some Twitter data sets and show great performances with respect to Heaps' law and, above all, with respect to the fitting of the frequency-rank plots for low and high frequencies. Moreover, we also give other examples of update functions, that are able to reproduce the behaviors empirically observed in other contexts.


Intra- and inter-rater reliability of Fugl-Meyer Assessment of Lower Extremity early after stroke.
The Fugl-Meyer Assessment of Lower Extremity (FMA-LE) is a widely used and recommended scale for evaluation of post-stroke motor impairment. However, the reliability of the scale has only been established by using parametric statistical methods, which ignores the ordinal properties of the scale. To determined intra- and inter-rater reliability of the FMA-LE at item and summed score level early after stroke. Sixty patients (mean age 65.9 years, median FMA-LE 29 points) admitted to the hospital due to stroke were included. The FMA-LE was simultaneously, but independently, scored by three experienced and trained physical therapists randomly assigned into pairs, on two consecutive days, between 4 to 9 days post stroke. A rank-based statistical method for paired ordinal data was used to assess the level of agreement and systematic and random disagreements. The item-level reliability was high (percentage of agreement [PA] ≥75%). Two items (ankle dorsiflexion during flexor synergy and normal reflex activity) showed some systematic disagreement in intrarater analysis. A satisfactory intrarater reliability (PA ≥70%) was reached for all summed scores when a 1- or 2-point difference was accepted between ratings. The FMA-LE is a reliable tool for assessment of motor impairment both within and between raters early after stroke. The scale can be recommended not only for use in Spanish speaking countries, but also internationally. A unified international use of FMA-LE would allow comparison of stroke recovery outcomes worldwide and thereby potentially improve the quality of stroke rehabilitation.


Copeptin in aneurysmal subarachnoid hemorrhage.
Copeptin is a peptide derived from pre-provasospression along with arginine vasospressin. In the setting of aneurysmal subarachnoid hemorrhage (SAH), elevated serum copeptin levels correlate with vasospasm, inpatient mortality, mortality at 1 year, and poor functional outcome at 1 year. The potential role of serum copeptin levels in the management of patients with aneurysmal SAH is promising and should be explored further.


Predictors for false-negative QuantiFERON-TB Gold assay results in patients with extrapulmonary tuberculosis.
Extrapulmonary tuberculosis (EPTB) is a heterogeneous disease, and diagnosis is sometimes difficult. We investigated the diagnostic performance of the QuantiFERON-TB Gold assay (QFT-GIT) according to sites of EPTB and predictors for false-negative QFT-GIT results. A total of 2176 patients were registered with active TB from January 2012 to December 2016 in Seoul St. Mary's Hospital, a 1200-bed tertiary teaching hospital in Seoul, Korea. We retrospectively reviewed the medical records of 163 EPTB patients who underwent QFT-GIT. False negative QFT-GIT results were found in 28.8% (95% CI 0.22-0.36) of patients with EPTB. In the proven TB group, negative QFT-GIT results were found in 28.6% (95% CI 0.04-0.71) of pleural, 8.3% 0.002-0.38of lymph node, 8.3% (95% CI 0.002-0.38) of skeletal and 5.8% (95% CI 0.001-0.28) of gastrointestinal TB cases. Among probable TB cases, QFT-GIT negative results were identified in 46.2% (95% CI 0.19-0.75) of skeletal, 33.3% (95% CI 10-0.65) of pericardial, 30.8% (95% CI 0.09-0.61) of pleural and 17.2% (95% CI 0.10-0.56) of gastrointestinal TB cases. In the possible TB cases, central nervous system TB (n = 21) was most frequent, and 66.7% (95% CI 0.43-0.85) of those showed QFT-GIT negative results. By multivariate analysis, possible TB was independently associated with false-negative QFT-GIT results (OR 4.92, 95% CI 1.51-16.06, p = 0.008). Prudent interpretation of QFT-GIT results might be needed according to anatomic site of involvement and diagnostic criteria in patients with high suspicion of EPTB.


Interpretation of UV-survival curves of Aspergillus conidiospores.
Semi-logarithmic dose-response curves for survival of UV-irradiated conidiospores of A. nidulans have an initial shoulder (at low doses) followed by a decline which becomes linear. To explain the initial shoulder and the resulting extrapolation number (log S intercept of the linear extrapolation line) a general model is presented, which includes multi-target (n) and multi-hit (h) effects and allows for the effect of initial repair and of a compound parameter k, which stands for inherent sensitivity of the spores and for dose received inside the spores. From experiments on (a) the modification of k (spore wall colour and shelter effects), (b) a repair-deficient strain (shoulderless) and (c) preincubation during which DNA-replication takes place, it is concluded that the shoulder is generated by initial repair rather than by a multi-hit nature of the cell-killing process. In experiments where k takes different values (sub a and c), notably the position of the point of intersection of the linear lines gives conclusive information. In general, the log S intercept of the linear extrapolation line cannot be used to estimate the target number.


Development of one experimental module to study the modulation of the propagation velocity of chemical excitation waves in gel by weak external force (gravity).
Biological and chemical systems in which the pattern of flow of energy and matter imposes self-organization can be seen as examples of excitable media. One property of such media is the presence of excitation waves. The Belouzov-Zabotinsky(B-Z) reaction system and the retinal spreading depression wave are examples of experimental models of excitable media in which the influence of gravity can be studied. In this paper we describe one especial module constructed to test the influence of gravity in gels of the B-Z system. In the gel condition, convection effects are minimized. The results will be directly comparable to retinal experiments programmed by the same group and complete a series of investigations of systematic comparison of the modulation of chemical and biological excitation waves by weak external forces.


MRI measurements the linear volume of posterior cranial fossa in patients with hemifacial spasm.
To explore the pathogenesis of hemifacial spasm (HFS) and the effect of posterior fossa volume on postoperative complications. The measurements of the antero-posterior diameter of foramen magnum, the length of supraocciput, the angle of tentorium cerebelli, clivus and occipital bone were performed on MRI. The data of measurements and postoperative complications were then analyzed and statistically examined. The antero-posterior diameter of the foramen magnum was smaller in HFS group (34.98 ± 2.83) mm than in control group (35.83 ± 2.67) mm (P < 0.05); The length of supraocciput was smaller in HFS group (44.67 ± 4.48) mm than in control group (45.84 ± 4.25) mm (P < 0.05); The angle of tentorium cerebelli was larger in HFS group (41.03 ± 5.01)°than in control group (37.28 ± 4.31)° (P < 0.05); The angle of clivus was smaller in HFS group (52.71 ± 6.22)° than in control group (56.39 ± 6.61)° (P < 0.05). The operation time was significantly longer in crowding group (107.90 ± 26.20) min than in non-crowding group (96.48 ± 20.52) min (P < 0.05); The incidence of postoperative facial paralysis was significantly higher in crowding group (16.19%) than in non-crowding group (7.20%) (P < 0.05); The incidence of postoperative hearing loss was significantly higher in crowding group (13.33%) than in non-crowding group (4.00%) (P < 0.05). Factors such as shorter antero-posterior diameter of foramen magnum, lower tentorium cerebelli, and shorter length of supraocciput in patients with HFS indicate the posterior fossa dysplasia and promote the occurrence of HFS. The crowding of the posterior fossa will increase the difficulty of the surgery and the incidence of postoperative facial paralysis and hearing loss.


Role of S-nitrosylation in apoptosis resistance and carcinogenesis.
Nitric oxide (NO) has been widely recognized as a positive regulator of tumorigenesis and cancer progression through its ability to regulate important proteins in various signal transduction pathways. S-Nitrosylation, or covalent attachment of NO to protein sulphydryl groups, has gained prominence as an important mechanism by which NO modulates physiologic and pathologic cellular responses. In this article, we discuss S-nitrosylation of two key apoptosis-regulatory proteins of the intrinsic and extrinsic death pathways, namely B-cell lymphoma-2 (Bcl-2) and FLICE-inhibitory protein (FLIP). These proteins have been shown to be upregulated in a variety of tumors and have been implicated with cancer chemoresistance through dysregulation of apoptosis. S-Nitrosylation of these proteins precludes their ubiquitination and subsequent degradation by the proteasome, thus accentuating their anti-apoptotic effect which is critical in the context of tumorigenic potential and cancer progression. We propose that such post-translational modifications of proteins by NO may be a general mechanism that tumor cells exploit to tilt the scales towards survival and proliferation by evading cell death.


Organization of mini-exon and 5S rRNA genes in the kinetoplastid Trypanoplasma borreli.
Mini-exon gene repeats from Trypanoplasma borreli, which belongs to the Cryptobiidae family of the Bodonina suborder of the Kinetoplastida, were isolated by PCR amplification and cloning. The presence of kinetoplastid-like mini-exon genes in T. borreli is consistent with the taxonomic status of this organism as a kinetoplastid protozoan. Two families of repeats were found: 597 nt (T1) and 794 nt (T2), each of which encodes an approximately 95-nt medRNA transcript. The T1 repeats also contain a complete 5S rRNA gene on the complementary strand. The T2 repeats contain a defective copy of a 5S gene, in which the 5' portion is absent. The intergenic regions between the 5'-ends of the mini-exon genes and the 5S rRNA genes in the T1 and T2 repeats are highly diverged. All or most mini-exon genes and 5S genes are located within either the T1 or the T2 repeats. The T1 repeats were localized to a megabase-size chromosome, while the T2 repeats were localized within at least 4 large chromosomes.


Developing and comparing models of hematopoietic-acute radiation syndrome in Göttingen and Sinclair minipigs.
Current animal models of hematopoietic-acute radiation syndrome (H-ARS) are resource intensive and have limited translation to humans, thereby inhibiting the development of effective medical countermeasures (MCM)s for radiation exposure. To improve the MCM pipeline, we developed models of H-ARS in male Göttingen and Sinclair minipigs. Weight matched Göttingens and Sinclairs received total body irradiation (TBI; 1.50-2.10 Gy and 1.94-2.90 Gy, respectively), were observed for up to 45 days with blood collections for clinical pathology analysis, and were examined during gross necropsy. The lethal dose for 50% of the population over the course of 45 days (LD50/45) with 'field' supportive care (primarily antibiotics and hydration support) and implanted vascular access ports was 1.89 and 2.53 Gy for Göttingens and Sinclairs, respectively. Both minipig strains exhibited prototypical H-ARS characteristics, experiencing thrombocytopenia and neutropenia, and nadirs approximately 14 days following irradiation, slightly varying with dose. Both strains experienced increased bruising, petechia, and signs of internal hemorrhage in the lungs, GI, heart, and skin. All observations were noted to correlate with dose more closely in Sinclairs than in Göttingens. The results of this study provide a template for future MCM development in an alternate species, and support further development of the Göttingen and Sinclair minipig H-ARS models.


Fine structure of the cerebellum of "staggerer-reeler", a double mutant of mice affected by staggerer and reeler conditions. III. bergmann fiber anomalies.
Bergmann fibers and the distribution of Golgi epithelial cells were significantly altered in staggerer, reeler and double mutant (affected by both staggerer and reeler conditions). However, the Bergmann fiber anomalies in double mutant were not identical to those of either staggerer or reeler. A comparison of these anomalies with the anomalies described in weaver revealed that the developmental patterns of Bergmann fibers are distinct in all four cerebellar mutants just as are the cytoarchitectural anomalies of these cerebella. The results of the present electronmicroscopic examinations of Bergmann fibers in staggerer and reeler were in good agreement with the findings made with the immunofluorescence technique. There was, however, one important discrepancy between these two sets of observations. Immunofluorescent astrocytic fibers were nearly absent in 21 and 26 day old staggerers while Bergmann fibers were structurally present in nearly normal numbers both at days 21 and 31. A possible reason for this discrepancy was discussed.


Marginal differentiation between the sexual and general carotenoid pigmentation of guppies (Poecilia reticulata) and a possible visual explanation.
We present the first detailed analysis of carotenoid pigmentation of the integument of guppies (Poecilia reticulata Peters), quantifying variation in carotenoid content and composition of wild guppies from three drainages on Trinidad (1) between the sexual and general pigmentation of males, (2) between the sexes, and (3) geographically in relation to carotenoid availability. We report that the carotenoid pigments in the integument of guppies are predominantly esters of tunaxanthin. The peak wavelength of carotenoids in the orange spots of males lay only ca. 2.8 nm higher than that of pigments outside of the orange spots, and the peak wavelength of carotenoids in the male whole integument does not differ from that in the female whole integument. Carotenoid composition of the general integument of females and the non-orange spot fraction of males, but not of the orange spot fraction of males, varied with diet, correlating with the ratio beta-carotene to lutein in the different streams. Male guppies deposit higher concentrations of carotenoids in their orange spots than in the rest of the integument (five to nine times higher), but not at the expense of the general integument, which was similarly endowed as the general integument of females, even in carotenoid-poor streams. Presumably males absorb/retain more pigments than females. Photoreceptor-based simulations suggest that tunaxanthin provides both greater brightness and chroma than would 4-keto-carotenoids such as astaxanthin.


[An expert consulting system for the epidemiologic physician].
The questions relating to the practical use of the automated expert system for diagnostics, the type of the epidemiological process and giving recommendations for carrying out single purpose prophylactic and antiepidemic measures has been considered herein. The peculiarities of use of the present system with micro-computer has been described.


Effect of a sphingolipid-mimetic compound on the promotion of hair growth: A randomized, double-blind, placebo-controlled clinical trial.
Pattern hair loss is a very common skin disorder, but more therapeutic modalities for hair growth are still required. We investigated the effect of a newly synthesized sphingolipid-mimetic compound (pseudo-ceramide: bis-oleamide isopropyl alcohol [BOI]) on the promotion of hair growth for patients with mild pattern hair loss. A total of 58 patients with mild pattern hair loss participated in this clinical trial. A randomized, double-blind, placebo-controlled clinical trial was conducted for 6 months. Participants in the experimental group applied 1% BOI lotion (ceramide HS) on the whole scalp once a day for 6 months. Participants in the control group applied simulacrum using the same protocol. We evaluated daily hair loss, hair density, hair thickness, and hair length at intervals of 3 months; patient satisfaction and adverse events were evaluated at 6 months. At 6 months in the experimental group, daily hair loss at baseline (52.52 ± 33.98) decreased to 40.41 ± 24.78, vertex hair density at baseline (131.07 ± 43.73) increased to 156.00 ± 39.59, frontal hair density at baseline (104.21 ± 30.72) increased to 124.10 ± 28.28, thickness of vertex hair at baseline (0.067 ± 0.012 cm) increased to 0.075 ± 0.014 cm, thickness of frontal hair at baseline (0.070 ± 0.009 cm) increased to 0.076 ± 0.012 cm, and hair growth rate was 16.17 ± 1.89 mm/month. Ceramide HS may be a new candidate for the treatment of pattern hair loss.


Innate immune response gene expression profiles characterize primary antiphospholipid syndrome.
Primary antiphospholipid syndrome (PAPS) is a systemic autoimmune disorder characterized by thromboembolic episodes and pregnant morbidity with an increasing clinical importance. To gain insight into the pathogenesis of PAPS, we have investigated the gene expression profiles that characterize peripheral blood mononuclear cells derived from PAPS patients. We show that the transcriptional activity of genes involved in innate immune responses, such as toll-like receptor 8 and CD14, as well as downstream genes of this pathway, such as STAT1, OAS2, TNFSF13 and PLSCR1 are significantly increased in PAPS patients. In addition, the expression of monocyte-specific cytokines is also elevated in PAPS mononuclear cells stimulated in vitro with lipopolysaccharide. Taken together, these results reveal a 'response to pathogen' signature in PAPS, which could reflect an altered monocyte activity. Finally, microarray analyses also revealed a reduced expression of genes coding for proteins involved in transcriptional control. Interestingly, a significant proportion of them exhibit E2F-binding sites in their promoter, suggesting that a deregulated RB/E2F activity could play a role in the pathogenesis of antiphospholipid syndrome.


Gold-catalyzed oxidative reactions of propargylic carbonates involving 1,2-carbonate migration: stereoselective synthesis of functionalized alkenes.
A gold-catalyzed oxidative reaction of propargylic carbonates or acetates using 3,5-dichloropyridine as the oxidant has been developed. The reaction provides efficient access to α-functionalized-α,β-unsaturated ketones with excellent regio- and diastereocontrol via a regioselective attack of the N-oxide to the gold-activated alkyne followed by a 1,2-carbonate migration. In addition, the alkene products could be further transformed into the valuable 5-hydroxycyclopent-2-enones via cyclocondensation with acetone or cyclodimerization under basic conditions.


Functional interactions between the oxytocin receptor and the β2-adrenergic receptor: implications for ERK1/2 activation in human myometrial cells.
The Gq-coupled oxytocin receptor (OTR) and the Gs-coupled β(2)-adrenergic receptor (β(2)AR) are both expressed in myometrial cells and mediate uterine contraction and relaxation, respectively. The two receptors represent important pharmacological targets as OTR antagonists and β(2)AR agonists are used to control pre-term uterine contractions. Despite their physiologically antagonistic effects, both receptors activate the MAP kinases ERK1/2, which has been implicated in uterine contraction and the onset of labor. To determine the signalling pathways involved in mediating the ERK1/2 response, we assessed the effect of blockers of specific G protein-associated pathways. In human myometrial hTERT-C3 cells, inhibition of Gαi as well as inhibition of the Gαq/PKC pathway led to a reduction of both OTR- and β(2)AR-mediated ERK1/2 activation. The involvement of Gαq/PKC in β(2)AR-mediated ERK1/2 induction was unexpected. To test whether the emergence of this novel signalling mechanism was dependent on OTR expression in the same cell, we conducted experiments in HEK 293 cells that were transfected with the β(2)AR alone or co-transfected with the OTR. Using this approach, we found that β(2)AR-mediated ERK1/2 responses became sensitive to PKC inhibition only in cells co-transfected with the OTR. Inhibitor studies indicated the involvement of an atypical PKC isoform in this process. We confirmed the specific involvement of PKCζ in this pathway by assessing PKCζ translocation to the cell membrane. Consistent with our inhibitor studies, we found that β(2)AR-mediated PKCζ translocation was dependent on co-expression of OTR. The present demonstration of a novel β(2)AR-coupled signalling pathway that is dependent on OTR co-expression is suggestive of a molecular interaction between the two receptors.


Editorial Commentary: Postoperative Outcomes-Are We Asking the Right Questions? Shoulder Arthroscopy Patient Quality of Life Correlates With Joint-Specific Outcome and Is Predicated on Patient Expectation.
Patient-reported outcomes are, by definition, subjective, and there is consensus that individual patient expectations have a significant effect on the postoperative outcome after shoulder arthroscopy. Most of the outcomes in orthopaedic surgery are measured either in terms of functional scores assessing only one joint or as disease or condition-specific outcomes. As such, there exists a growing interest developing better tools to measure quality-of-life outcome scores as an assessment of overall patient health and satisfaction. Recent research shows that quality-of-life outcome measures correlate with joint-specific and functional outcomes after arthroscopic Bankart repair. We also personally believe that quality-of-life scores should become a standard outcome assessment measurement in orthopaedic surgery because while we perform surgery on the joint, we take care of the whole patient.


Combined full-length transcriptomic and metabolomic analysis reveals the regulatory mechanisms of adaptation to salt stress in asparagus.
Soil salinity is a very serious abiotic stressor that affects plant growth and threatens crop yield. Thus, it is important to explore the mechanisms of salt tolerance of plant and then to stabilize and improve crop yield. Asparagus is an important cash crop, but its salt tolerance mechanisms are largely unknown. Full-length transcriptomic and metabolomic analyses were performed on two asparagus genotypes: 'jx1502' (a salt-tolerant genotype) and 'gold crown' (a salt-sensitive genotype). Compared with the distilled water treatment (control), 877 and 1610 differentially expressed genes (DEGs) were identified in 'jx1502' and 'gold crown' under salt stress treatment, respectively, and 135 and 73 differentially accumulated metabolites (DAMs) were identified in 'jx1502' and 'gold crown' under salt stress treatment, respectively. DEGs related to ion transport, plant hormone response, and cell division and growth presented differential expression profiles between 'jx1502' and 'gold crown.' In 'jx1502,' 11 ion transport-related DEGs, 8 plant hormone response-related DEGs, and 12 cell division and growth-related DEGs were upregulated, while 7 ion transport-related DEGs, 4 plant hormone response-related DEGs, and 2 cell division and growth-related DEGs were downregulated. Interestingly, in 'gold crown,' 14 ion transport-related DEGs, 2 plant hormone response-related DEGs, and 6 cell division and growth-related DEGs were upregulated, while 45 ion transport-related DEGs, 13 plant hormone response-related DEGs, and 16 cell division and growth-related DEGs were downregulated. Genotype 'jx1502' can modulate K+/Na+ and water homeostasis and maintain a more constant transport system for nutrient uptake and distribution than 'gold crown' under salt stress. Genotype 'jx1502' strengthened the response to auxin (IAA), as well as cell division and growth for root remodeling and thus salt tolerance. Therefore, the integration analysis of transcriptomic and metabolomic indicated that 'jx1502' enhanced sugar and amino acid metabolism for energy supply and osmotic regulatory substance accumulation to meet the demands of protective mechanisms against salt stress. This work contributed to reveal the underlying salt tolerance mechanism of asparagus at transcription and metabolism level and proposed new directions for asparagus variety improvement.