Total synthesis of (+/-)-lennoxamine and (+/-)-aphanorphine by intramolecular electrophilic aromatic substitution reactions of 2-amidoacroleins.
Intramolecular electrophilic aromatic substitution reactions of 2-amidoacroleins constitute the key steps in the total syntheses of lennoxamine and aphanorphine. The aldehyde moiety of one cyclization product was transformed to a double bond, which was then engaged in a radical cyclization to produce the complete ring system of lennoxamine. The aldehyde functionality of the other cyclization product was converted to the corresponding mesylate, which underwent intramolecular displacement by a lactam enolate to furnish the ring system of aphanorphine. [reaction: see text]


An introduction to liquid chromatography-mass spectrometry instrumentation applied in plant metabolomic analyses.
Over the past decade the application of non-targeted high-throughput metabolomic analysis within the plant sciences has gained ever increasing interest and has truly established itself as a valuable tool for plant functional genomics and studies of plant biochemical composition. Whilst proton nuclear magnetic resonance ((1)H-NMR) spectroscopy is particularly appropriate for the analysis of bulk metabolites and gas chromatography mass spectrometry (GC-MS) to the analysis of volatile organic compounds (VOC's) and derivatised primary metabolites, liquid chromatography (LC)-MS is highly applicable to the analysis of a wide range of semi-polar compounds including many secondary metabolites of interest to plant researchers and nutritionists. In view of the recent developments in the separation sciences, leading to the advent of ultra high performance liquid chromatography (UHPLC) and MS based technology showing the ever improving resolution of metabolite species and precision of mass measurements (sub-ppm accuracy now being achievable), this review sets out to introduce the background and update the reader upon LC, high performance (HP)LC and UHPLC, as well as the large range of MS instruments that are being applied in current plant metabolomic studies. As well as covering the theory behind modern day LC-MS, the review also discusses the most relevant metabolomics applications for the wide range of MS instruments that are currently being applied to LC.


The Brl domain in Sec63p is required for assembly of functional endoplasmic reticulum translocons.
Protein translocation into the endoplasmic reticulum occurs at pore-forming structures known as translocons. In yeast, two different targeting pathways converge at a translocation pore formed by the Sec61 complex. The signal recognition particle-dependent pathway targets nascent precursors co-translationally, whereas the Sec62p-dependent pathway targets polypeptides post-translationally. In addition to the Sec61 complex, both pathways also require Sec63p, an integral membrane protein of the Hsp40 family, and Kar2p, a soluble Hsp70 located in the ER lumen. Using a series of mutant alleles, we demonstrate that a conserved Brl (Brr2-like) domain in the COOH-terminal cytosolic region of Sec63p is essential for function both in vivo and in vitro. We further demonstrate that this domain is required for assembly of two oligomeric complexes of 350 and 380 kDa, respectively. The larger of these corresponds to the heptameric "SEC complex" required for post-translational translocation. However, the 350-kDa complex represents a newly defined hexameric SEC' complex comprising Sec61p, Sss1p, Sbh1p, Sec63p, Sec71p, and Sec72p. Our data indicate that the SEC' complex is required for co-translational protein translocation across the yeast ER membrane.


Cloning of methylated transforming DNA from Neurospora crassa in Escherichia coli.
An arg-2 mutant of Neurospora crassa was transformed to prototrophy with a pBR322-N. crassa genomic DNA library. Repeated attempts to recover the integrated transforming DNA or segments thereof by digestion, ligation, and transformation of Escherichia coli, with selection for the plasmid marker ampicillin resistance, were unsuccessful. Analyses of a N. crassa transformant demonstrated that the introduced DNA was heavily methylated at cytosine residues. This methylation was shown to be responsible for our inability to recover transformants in standard strains of E. coli; transformants were readily obtained in a strain which is deficient in the two methylcytosine restriction systems. Restriction of methylated DNA in E. coli may explain the general failure to recover vector or transforming sequences from N. crassa transformants.


Contralateral suppression of otoacoustic emissions in tinnitus patients.
To compare the functioning of the medial olivocochlear efferent system between tinnitus patients and control subjects. Prospective, nonrandomized controlled analysis of suppression of otoacoustic emissions with contralateral acoustic stimulation. Tertiary referral center. Initial analysis of 97 tinnitus patients and 44 control subjects with click-evoked otoacoustic emission measurement. If subjects had reproducible otoacoustic emissions at 80 dB SPL, suppression of otoacoustic emission with contralateral acoustic stimulation was measured with a 65-dB click stimulus. This resulted in inclusion of 44 ears of tinnitus patients and 57 ears of control subjects. Suppression of the otoacoustic emissions generated by the 65-dB click stimulus was tested using contralateral broadband noise at 70 dB SPL. Suppression was calculated in half-octave frequency bands centered at 1.0, 1.4, 2.0, 2.8, and 4.0 kHz. The amount of suppression of the OAE, calculated in half-octave frequency bands. Otoacoustic emission amplitudes were equal in both groups. Contralateral suppression of the signal was found in both patients and controls. The amount of suppression was equal, except for the 2.0- and 2.8-kHz frequency bands in the right ear (p value of 0.03, 0.008, respectively), for which the patients had less suppression. The suppression of otoacoustic emissions with CAS seems equally effective in tinnitus patients and healthy controls. The minor differences between both groups suggest subtle differences in the function of the medial olivocochlear efferent system.


Simultaneous HPLC-UV determination of ketamine, xylazine, and midazolam in canine plasma.
An isocratic reversed-phase high-performance liquid chromatography method with UV detection is developed and validated for the simultaneous determination of ketamine, xylazine, and midazolam in canine plasma. Analytes are extracted from alkalinized samples into diethyl ether-methylene chloride (7:3, v:v) using single-step liquid-liquid extraction. Chromatographic separation is performed on a C(18) column using a mobile phase containing an acetonitrile-methanol-10 mM sodium heptanesulfonate buffer adjusted to pH 3, with glacial acetic acid (44:10:46, v:v) at a detection wavelength of 210 nm, with a total runtime of 10 min. The calibration is linear over the range of 78.125-5000 ng/mL for ketamine and 15.625-1000 ng/mL for xylazine and midazolam. The limits of detection are 17.8, 10.3, and 15.1 ng/mL for ketamine, xylazine, and midazolam, respectively. The extraction recoveries are 76.1% for ketamine, 91.0% for midazolam, and 78.2% for xylazine. The method is successfully used for clinical and pharmacokinetic studies of the three-drug fixed dose combination formulations.


An RNAi based screen in Drosophila larvae identifies fascin as a regulator of myoblast fusion and myotendinous junction structure.
A strength of Drosophila as a model system is its utility as a tool to screen for novel regulators of various functional and developmental processes. However, the utility of Drosophila as a screening tool is dependent on the speed and simplicity of the assay used. Here, we use larval locomotion as an assay to identify novel regulators of skeletal muscle function. We combined this assay with muscle-specific depletion of 82 genes to identify genes that impact muscle function by their expression in muscle cells. The data from the screen were supported with characterization of the muscle pattern in embryos and larvae that had disrupted expression of the strongest hit from the screen. With this assay, we showed that 12/82 tested genes regulate muscle function. Intriguingly, the disruption of five genes caused an increase in muscle function, illustrating that mechanisms that reduce muscle function exist and that the larval locomotion assay is sufficiently quantitative to identify conditions that both increase and decrease muscle function. We extended the data from this screen and tested the mechanism by which the strongest hit, fascin, impacted muscle function. Compared to controls, animals in which fascin expression was disrupted with either a mutant allele or muscle-specific expression of RNAi had fewer muscles, smaller muscles, muscles with fewer nuclei, and muscles with disrupted myotendinous junctions. However, expression of RNAi against fascin only after the muscle had finished embryonic development did not recapitulate any of these phenotypes. These data suggest that muscle function is reduced due to impaired myoblast fusion, muscle growth, and muscle attachment. Together, these data demonstrate the utility of Drosophila larval locomotion as an assay for the identification of novel regulators of muscle development and implicate fascin as necessary for embryonic muscle development.


[Biomarkers for early screening and diagnosis of breast cancer: a review].
The estimated new cases of breast cancer (BC) patients were 2.26 million in 2020, which accounted for 11.7% of all cancer patients, making it the most prevalent cancer worldwide. Early detection, diagnosis and treatment are crucial to reduce the mortality, and improve the prognosis of BC patients. Despite the widespread use of mammography screening as a tool for BC screening, the false positive, radiation, and overdiagnosis are still pressing issues that need to be addressed. Therefore, it is urgent to develop accessible, stable, and reliable biomarkers for non-invasive screening and diagnosis of BC. Recent studies indicated that the circulating tumor cell DNA (ctDNA), carcinoembryonic antigen (CEA), carbohydrate antigen 15-3 (CA15-3), extracellular vesicles (EV), circulating miRNAs and BRCA gene from blood, and the phospholipid, miRNAs, hypnone and hexadecane from urine, nipple aspirate fluid (NAF) and volatile organic compounds (VOCs) in exhaled gas were closely related to the early screening and diagnosis of BC. This review summarizes the advances of the above biomarkers in the early screening and diagnosis of BC.


The Clinical Effect of Seasonal Flu Vaccination on Health-Related Quality of Life.
This study aimed to determine the clinical effect of seasonal flu vaccination in adult outpatients based on the effect on health-related quality of life (HRQOL). We reviewed the clinical data of adult flu outpatients with mild symptoms who presented to the outpatient clinic of Teikyo University Hospital, Tokyo, Japan, from 2018 to 2020 winter season and were enrolled in the prospective observational study of the clinical efficacy of anti-flu agents (UMIN000034896). We evaluated influenza vaccination status, clinical symptoms, and the status of HRQOL as measured by Short Form-8® (SF-8®) at first visit. The SF-8® survey generated two-component summaries; a physical component summary and a mental component summary. The data of 79 patients were evaluated in this study. Of the 79 patients, 37 were vaccinated for influenza at least three weeks before contracting seasonal influenza. Not every patient needed to be hospitalized for treatment. There were no significant differences in clinical backgrounds between vaccinated patients and non-vaccinated patients. Univariate analysis showed influenza vaccination was significantly associated with higher scores on the physical component summary of HRQOL (p=0.0011). Influenza vaccinations would be clinically valuable for adult outpatients with seasonal flu and mild symptoms, because they can significantly inhibit the decrease of HRQOL due to influenza infection.


RNA secondary structure prediction with pseudoknots: Contribution of algorithm versus energy model.
RNA is a biopolymer with various applications inside the cell and in biotechnology. Structure of an RNA molecule mainly determines its function and is essential to guide nanostructure design. Since experimental structure determination is time-consuming and expensive, accurate computational prediction of RNA structure is of great importance. Prediction of RNA secondary structure is relatively simpler than its tertiary structure and provides information about its tertiary structure, therefore, RNA secondary structure prediction has received attention in the past decades. Numerous methods with different folding approaches have been developed for RNA secondary structure prediction. While methods for prediction of RNA pseudoknot-free structure (structures with no crossing base pairs) have greatly improved in terms of their accuracy, methods for prediction of RNA pseudoknotted secondary structure (structures with crossing base pairs) still have room for improvement. A long-standing question for improving the prediction accuracy of RNA pseudoknotted secondary structure is whether to focus on the prediction algorithm or the underlying energy model, as there is a trade-off on computational cost of the prediction algorithm versus the generality of the method. The aim of this work is to argue when comparing different methods for RNA pseudoknotted structure prediction, the combination of algorithm and energy model should be considered and a method should not be considered superior or inferior to others if they do not use the same scoring model. We demonstrate that while the folding approach is important in structure prediction, it is not the only important factor in prediction accuracy of a given method as the underlying energy model is also as of great value. Therefore we encourage researchers to pay particular attention in comparing methods with different energy models.


Differential adherence of murine hematopoietic stem cell subsets to fibronectin.
Growth and differentiation of hematopoietic stem cells occur in close contact with the cells and extracellular-matrix (ECM) proteins of the hematopoietic microenvironment. We observed the role of fibronectin, a matrix glycoprotein proposed to be involved in the attachment of hematopoietic cells and in the binding of stem cell subsets to bone marrow stroma, for this study. Murine bone marrow cells (BMC) were allowed to adhere to surfaces coated with human plasma fibronectin. Using the cobblestone-area-forming cells (CAFC) assay, adherent and nonadherent cell fractions were tested for their quantity of primitive and less primitive stem cell subsets. The CAFC assay is based on a time-dependent clone formation in pre-established, bone marrow-derived, irradiated stromal layers under limiting dilution conditions, and it allows in vitro enumeration of day-12 colony-forming unit-spleen (CFU-S12) (CAFC-10) and more primitive cells with long-term repopulating abilities (LTRA) (CAFC-28/35). We observed that the majority of primitive CAFC-28/35 adhered to fibronectin, while only a minority of CFU-S-like CAFC-10 did. The adherence of primitive stem cells to fibronectin could partially be blocked by high molar concentrations of oligopeptides containing the essential amino acid sequence of the central cell-binding domain of fibronectin, RGD. Adherence of the small subpopulation of CAFC-10 to fibronectin could almost entirely be prevented by oligopeptides organized in a specific fashion. These data suggest a role for RGD-binding integrins in the adherence of hematopoietic stem cells.


Fowl aviadenovirus serotype 1 confirmed as the aetiological agent of gizzard erosions in replacement pullets and layer flocks in Great Britain by laboratory and in vivo studies.
An investigation into the aetiology and pathogenesis of adenoviral gizzard erosion has been conducted following three natural outbreaks affecting one flock of 6-week-old replacement pullets and two consecutive placements of free range layers at the age of 21 and 23 weeks. Affected flocks showed increased mortality (0.12-0.30% per week), and gizzard lesions were consistent with fowl aviadenovirus (FAdV) involvement. To substantiate the initial findings, a selection of archived formalin-fixed paraffin-embedded gizzard samples from another 12 pullet and layer flocks, for which macroscopic and histopathological diagnosis of the disease were recorded in Great Britain during the period 2009-2016, were also investigated. In situ hybridization (ISH), virology and/or PCR confirmed the presence of FAdV species-A, serotype-1 (FAdV-A, FAdV-1) DNA in gizzard samples of all 15 cases investigated. Co-infections with additional FAdV serotypes including FAdV-8a were detected by serology and/or virology in two of the pullet flocks. However, species-specific in situ hybridization revealed that pathological changes of affected gizzards were only associated with the detection of FAdV-A. A subsequent in vivo study infecting 21-day-old SPF pullets with FAdV-1 or FAdV-8a strains isolated from the 6-week-old replacement pullets revealed characteristic pathomorphological changes only in the gizzards from birds infected with FAdV-1. While infection with FAdV-8a was confirmed by virology and serology, infected SPF birds did not develop pathomorphological changes. Therefore, the aetiological involvement of the isolated FAdV-8a in the development of adenoviral gizzard erosion in commercial pullets has been ruled out.


Patch-Based Super-Resolution of MR Spectroscopic Images: Application to Multiple Sclerosis.
Purpose: Magnetic resonance spectroscopic imaging (MRSI) provides complementary information to conventional magnetic resonance imaging. Acquiring high resolution MRSI is time consuming and requires complex reconstruction techniques. Methods: In this paper, a patch-based super-resolution method is presented to increase the spatial resolution of metabolite maps computed from MRSI. The proposed method uses high resolution anatomical MR images (T1-weighted and Fluid-attenuated inversion recovery) to regularize the super-resolution process. The accuracy of the method is validated against conventional interpolation techniques using a phantom, as well as simulated and in vivo acquired human brain images of multiple sclerosis subjects. Results: The method preserves tissue contrast and structural information, and matches well with the trend of acquired high resolution MRSI. Conclusions: These results suggest that the method has potential for clinically relevant neuroimaging applications.


Severe hepatic involvement in visceral larva migrans.
Because of its anatomical position, the liver may be involved in many protozoan and helminthic gastrointestinal infections. Visceral larva migrans caused by Toxocara canis is rarely taken into account in adult patients with cholestatic syndrome, especially when liver disease is not associated with hypereosinophilic reaction. We report on a 74-year-old immunocompetent woman who presented with fever, bronchospasm, erythema nodosum, weight loss and progressive jaundice. A liver biopsy showed caseating granulomatous hepatitis with secondary portal fibrosis and paucity of interlobular bile ducts. A step-by-step search for aetiological factors led us to a diagnosis of toxocariasis (positive enzyme-linked immunosorbent assay IgG test). An excellent clinical response to combined treatment with steroid and diethylcarbamazine, and a reduction in the antibody level against T. canis supported the diagnosis. Computed tomography and laparoscopy demonstrated multiple small mass lesions and fibrous perihepatitis. This report shows that visceral larva migrans may be a cause of prostrating chronic liver disease and should be suspected in every febrile patient with cryptogenic cholestatic hepatitis.


Two multi-copper-containing heteropolyoxotungstates constructed from the lacunary Keggin polyoxoanion and the high-nuclear spin cluster.
Two novel high-nuclear copper-substituted polyoxometalates, Na16[Cu14(OH)4(H2O)16(SiW8O31)4].20.5H2O (1) and K10Na14[Cu10(H2O)2(N3)4(GeW9O34)2(GeW8O31)2].30H2O (2), containing 14 Cu2+ ions and 10 Cu2+ ions, respectively, have been obtained in aqueous solution and characterized by IR, UV, TG, element analysis, electrochemistry, and single-crystal X-ray analyses. The polyoxoanion framework of 1 is composed of four [beta-SiW8O31] units connected by 14 Cu2+ ions to constitute a tetrameric compound. In 2, two [beta-GeW8O31] anions and two [B-alpha-GeW9O34] anions are connected together by a [Cu10(N3)4O32(H2O)2] {Cu10(N3)4} cluster to construct a novel tetrameric compound. The results of the electrocatalytic experiments reveal that the reduced species of 1 and 2 have electrocatalytic activities for nitrate reduction.


Quo Vadis?: Russia's health challenges.
The roots of the health crisis in the Russian Federation are not entirely, or even primarily, in the state of the health care system. High levels of mortality and morbidity, particularly among working-age males, reflect many other factors that transcend the health system as they are related to the aging of the population, growing urbanization, lifestyles and risky behaviours. Spending more money on healthcare, while necessary, will not be sufficient to improve Russia's health outcomes on a sustainable basis. A multisectoral strategy is required, coupled with increased health expenditures and structural reforms to improve the efficiency and effectiveness of healthcare organization, financing and service delivery. However, it should be clear that improving health outcomes is a complex, medium- to long-term undertaking that should be addressed forcefully by the government at the federal and regional levels as a priority social objective.


The influence of light quality on C4 photosynthesis under steady-state conditions in Zea mays and Miscanthus×giganteus: changes in rates of photosynthesis but not the efficiency of the CO2 concentrating mechanism.
Differences in light quality penetration within a leaf and absorption by the photosystems alter rates of CO(2) assimilation in C(3) plants. It is also expected that light quality will have a profound impact on C(4) photosynthesis due to disrupted coordination of the C(4) and C(3) cycles. To test this hypothesis, we measured leaf gas exchange, (13) CO(2) discrimination (Δ(13) C), photosynthetic metabolite pools and Rubisco activation state in Zea mays and Miscanthus × giganteus under steady-state red, green, blue and white light. Photosynthetic rates, quantum yield of CO(2) assimilation, and maximum phosphoenolpyruvate carboxylase activity were significantly lower under blue light than white, red and green light in both species. However, similar leakiness under all light treatments suggests the C(4) and C(3) cycles were coordinated to maintain the photosynthetic efficiency. Measurements of photosynthetic metabolite pools also suggest coordination of C(4) and C(3) cycles across light treatments. The energy limitation under blue light affected both C(4) and C(3) cycles, as we observed a reduction in C(4) pumping of CO(2) into bundle-sheath cells and a limitation in the conversion of C(3) metabolite phosphoglycerate to triose phosphate. Overall, light quality affects rates of CO(2) assimilation, but not the efficiency of CO(2) concentrating mechanism.


The role of the gap junction perinexus in cardiac conduction: Potential as a novel anti-arrhythmic drug target.
Cardiovascular disease remains the single largest cause of natural death in the United States, with a significant cause of mortality associated with cardiac arrhythmias. Presently, options for treating and preventing myocardial electrical dysfunction, including sudden cardiac death, are limited. Recent studies have indicated that conduction of electrical activation in the heart may have an ephaptic component, wherein intercellular coupling occurs via electrochemical signaling across narrow extracellular clefts between cardiomyocytes. The perinexus is a 100-200 nm-wide stretch of closely apposed membrane directly adjacent to connexin 43 gap junctions. Electron and super-resolution microscopy studies, as well as biochemical analyses, have provided evidence that perinexal nanodomains may be candidate structures for facilitating ephaptic coupling. This work has included characterization of the perinexus as a region of close inter-membrane contact between cardiomyocytes (<30 nm) containing dense clusters of voltage-gated sodium channels. Here, we review what is known about perinexal structure and function and the potential that the perinexus may have novel and pivotal roles in disorders of cardiac conduction. Of particular interest is the prospect that cell adhesion mediated by the cardiac sodium channel β subunit (Scn1b) may be a novel anti-arrhythmic target.


Computational Optimization of Image-Based Reinforcement Learning for Robotics.
The robotics field has been deeply influenced by the advent of deep learning. In recent years, this trend has been characterized by the adoption of large, pretrained models for robotic use cases, which are not compatible with the computational hardware available in robotic systems. Moreover, such large, computationally intensive models impede the low-latency execution which is required for many closed-loop control systems. In this work, we propose different strategies for improving the computational efficiency of the deep-learning models adopted in reinforcement-learning (RL) scenarios. As a use-case project, we consider an image-based RL method on the synergy between push-and-grasp actions. As a first optimization step, we reduce the model architecture in complexity, by decreasing the number of layers and by altering the architecture structure. Second, we consider downscaling the input resolution to reduce the computational load. Finally, we perform weight quantization, where we compare post-training quantization and quantized-aware training. We benchmark the improvements introduced in each optimization by running a standard testing routine. We show that the optimization strategies introduced can improve the computational efficiency by around 300 times, while also slightly improving the functional performance of the system. In addition, we demonstrate closed-loop control behaviour on a real-world robot, while processing everything on a Jetson Xavier NX edge device.


Axillary vein thrombosis induced by an increasingly popular oscillating dumbbell exercise device: a case report.
A 53 year-old male presented with a one-day history of a swollen arm and dull, aching pain in the right upper extremity. The patient reported commencing exercising daily over the prior week with a modified, oscillating dumbbell; commonly referred to as a Shake Weight. Imaging revealed an occlusive thrombus in the right axillary, proximal brachial and basilic veins. The patient was treated with a 24-hour tPA infusion followed by mechanical thrombectomy, balloon angioplasty, and stent placement for a residual thrombus and stenosis. The patient was discharged the following day on warfarin and aspirin. This is the first report of effort-induced thrombosis of the upper extremity following the use of a modified, oscillating dumbbell. Due to the growing popularity of modified dumbbells and the possible risk for axillary vein thrombosis, consideration should be made to caution consumers of this potential complication.


YfiT from Bacillus subtilis is a probable metal-dependent hydrolase with an unusual four-helix bundle topology.
YfiT, a 19-kDa polypeptide from Bacillus subtilis, belongs to a small sequence family with members predominantly from Gram positive bacteria. We have determined the crystal structure of YfiT in complex with Ni(2+) to a resolution of 1.7 A. YfiT exists as a dimer and binds Ni(2+) in a 1:1 stoichiometry. The protein has an unusual four-helix bundle topology and coordinates Ni(2+) in an octahedral geometry with three conserved histidines and three waters. Although there is no similarity in their overall structures, the coordination geometry of the metal and the residues that constitute the putative active site in YfiT are similar to those of metalloproteases such as thermolysin. Our structural analyses suggest that YfiT might function as a metal-dependent hydrolase.


Unfavorable outcomes (end-stage renal failure/death) in childhood onset systemic lupus erythematosus. A multicenter study in Paris and its environs.
Thirty of 118 cases of childhood onset systemic lupus erythematosus collected in the Parisian area had an unfavorable outcome. Thirteen patients evolved to end-stage renal failure. Seven survived with renal substitution therapy, and 6 other patients subsequently died. Most had diffuse proliferative glomerulonephritis, the pattern of glomerular disease classically responsible for end-stage renal failure. Three patients had membranous nephropathy with segmental lesions, a form of glomerulonephritis whose severe prognosis should be emphasized. In another patient, end-stage renal failure was precipitated by thrombotic microangiopathy. Seventeen other patients died and in most, the causes of death were multiple. In 7, death could be attributed to complications secondary to an infection and in 4 other cases to SLE exacerbation with severe organ involvement. Two patients died suddenly, another showed cardiac failure and another had malignant hypertension. Of the remaining 2 patients, one suffered anticoagulant therapy complications after treatment for renal artery stenosis and the second, an urothelial carcinoma. Unfavorable evolutions were high among patients coming from French departments and territories, and among North African patients. One may speculate that poor outcome is associated with ethnic characteristics or with socioeconomic factors. However, the problem of compliance with treatment is clearly an extremely important factor in the prognosis. Both end-stage renal failure and death were in some of our cases precipitated by treatment interruption, indicating an insufficient understanding of the importance of treatment in this chronic disease.


Tumor size-dependent elevations of serum gangliosides in patients with head and neck carcinomas.
Serum gangliosides were studied in 100 patients with benign or tumoral head and neck lesions. Whereas very few changes over the normal level were noticed in benign cases, 78% of patients with head and neck carcinomas had a significant elevation of serum gangliosides, mostly accounted for by GM3 and GD3. Such an increase was correlated with the observed tumor size, and the level of serum gangliosides returned to normal within one month after surgery. Follow-up of patients showed that further elevations of serum gangliosides were associated with relapses.


Suppression of Th1 and Th2 immune responses in mice by Sinomenine, an alkaloid extracted from the chinese medicinal plant Sinomenium acutum.
The present study was designed to investigate the effect of sinomenine (SIN), an alkaloid extracted from Sinomenium acutum, on Th1 and Th2 immune responses in mice. For this investigation, mice were S. C. immunized with ovalbumin (OVA) emulsified with complete Freund's adjuvant (day 0). Varying doses of SIN were orally administered daily over a period of 21 days, commencing on day 0. On day 21, anti-OVA IgG and proliferative responses of spleen cells to the antigen were measured. Anti-OVA IgG2a and IFN-gamma were measured as indicators of Th1 immune responses and anti-OVA IgG1, IgE, and IL-5 as those of Th2 responses. TGF-beta was measured as an indicator of Th3 immune responses. The results showed that treatment with SIN was followed by decreases in anti-OVA IgG and the antigen-specific splenocyte proliferation. Production of all isotypes of antibodies including anti-OVA IgG2a, IgG1 and IgE as well as secretion of cytokines such as IFN-gamma and IL-5 was suppressed by SIN, although the suppression of anti-OVA IgG2a and IFN-gamma by the alkaloid appeared to be greater than that of anti-OVA IgG1, IgE, and IL-5. In addition, SIN enhanced the secretion of TGF-beta. These results suggest that SIN appears to have suppressive effects on both Th1 and Th2 immune responses. The results also suggest that Th1 responses may be more preferentially suppressed by the Sinomenium acutum-derived alkaloid compared to Th2 responses. TGF-beta may at least in part contribute to the suppression of Th1 as well as Th2 immune responses.


Fast and Scalable Feature Selection for Gene Expression Data Using Hilbert-Schmidt Independence Criterion.
In computational biology, selecting a small subset of informative genes from microarray data continues to be a challenge due to the presence of thousands of genes. This paper aims at quantifying the dependence between gene expression data and the response variables and to identifying a subset of the most informative genes using a fast and scalable multivariate algorithm. A novel algorithm for feature selection from gene expression data was developed. The algorithm was based on the Hilbert-Schmidt independence criterion (HSIC), and was partly motivated by singular value decomposition (SVD). The algorithm is computationally fast and scalable to large datasets. Moreover, it can be applied to problems with any type of response variables including, biclass, multiclass, and continuous response variables. The performance of the proposed algorithm in terms of accuracy, stability of the selected genes, speed, and scalability was evaluated using both synthetic and real-world datasets. The simulation results demonstrated that the proposed algorithm effectively and efficiently extracted stable genes with high predictive capability, in particular for datasets with multiclass response variables. The proposed method does not require the whole microarray dataset to be stored in memory, and thus can easily be scaled to large datasets. This capability is an important attribute in big data analytics, where data can be large and massively distributed.


Do uterotrophic drugs increase the risk of fatal hemorrhagic brain stroke?
To evaluate whether uterotrophic agents increase the risk of fatal hemorrhagic brain stroke. Between 1991 and 1992, there were 230 maternal deaths among 2,420,000 pregnant women in Japan and the causes of these deaths was investigated in 1994. Using information provided in this report, we identified 35 women who died from or were assumed to die from hemorrhagic brain stroke. We assumed that 93% of women would have tried vaginal delivery. The risk of fatal hemorrhagic brain stroke after uterotrophic agent use was calculated according to the assumption that 5.0-40% of women received uterotrophic agents. Use of uterotrophic agents for induction/augmentation of labor was confirmed in five (14.3%) of the 35 women who died from hemorrhagic brain stroke. The incidence of fatal brain stroke after the use of uterotrophic agents was only significantly higher than that for spontaneous hemorrhagic brain stroke if these agents were administered in ≤ 6.0% of women. Because more than 6.0% of women received uterotrophic agents, these agents are unlikely to increase the risk of fatal hemorrhagic brain stroke.


Growth hormone and prolactin secretion in cultured somatomammotroph cells.
A somatomammotropic cell line (P0) derived from adult rat pituitaries has been maintained in culture for 2 yr. Secretion of GH and PRL by this cell line has been studied in response to hypophysiotropic peptides known to affect the release of both hormones as well as agents that affect second messenger systems in an attempt to characterize the stimulus-secretion mechanisms used by these cells. GH and PRL release during short term (4 h) incubations of P0 cells and primary cultures of dispersed rat pituitary cells was initially measured in response to GRF, TRH, vasoactive intestinal peptide (VIP), and SRIF. In P0 cells, the minimal effective dose of each of the hypophysiotropic peptides was comparable with respect to GH and PRL secretion. The effects of TRH and VIP were similar to those in freshly dispersed cells with respect to PRL release, whereas those of GRF and SRIF were less potent with respect to GH release. The stimulation of GH and PRL release in P0 cells by adenylate cyclase-related agents ((Bu)2 cAMP and forskolin) was comparable to that for GH secretion in mature somatotrophs but much greater than that of PRL release in mature lactotrophs. Stimulation of GH and PRL release in P0 cells by protein kinase C-related agents (diacylglycerol and phorbol ester) was also similar to that observed for GH release from mature pituitary cells, whereas minimal or undetectable effects were observed on PRL release from mature cells. The results indicate that the P0 somatomammotropic cell line possesses receptors, second messenger systems, and secretory characteristics of both somatotrophs and lactotrophs, although where differences exist, there is more resemblance to somatotrophs. They also demonstrate that the responses to each of the agents studied are bihormonal and appear to be regulated by a common mechanism.


Personality and clinical manifestations of tension headache.
The personality dimensions and clinical manifestations of tension headache were studied and compared with neurotics and normals. The results showed that the experimental group differed significantly from normals. Persons with tension headache were introverted and scored highly on neuroticism. They did not differ from neurotics in personality and clinical manifestations except in relation to hysterical and obsessive features.


The prognostic value of toll-like receptor5 and programmed cell death-ligand1 in patients with peripheral T-cell non-Hodgkin lymphoma.
TLR5 is expressed in a variety of tumors. However, the clinical impact of TLR5 in Peripheral T-cell non-Hodgkin lymphomas (PTCLs) remains unclear. We analyzed differentially expressed genes in PTCLs samples from Gene Expression Omnibus database. We examined TLR5 and programed cell death-ligand1 (PD-L1) expression by immunohistochemistry in PTCLs tissues. Gene expression profiling shown PD-L1 and TLR5 expression was higher in PTCLs than in normal samples. The rates of high TLR5 and PD-L1 expression were 12.5% and 45.8%. We found association between TLR5 and PD-L1 expression. Low TLR5 expression or high PD-L1 expression was correlated with shorter overall survival and inferior disease-free survival. Multivariate Cox regression analysis shown low TLR5 expression, high PD-L1 expression, gender, and high IPI score were prognostic factors (p < .05). PTCLs patients with low TLR5 expression and high PD-L1 expression had worse prognosis. TLR5 and PD-L1 may serve as potential therapeutic targets in PTCLs patients.


IL-12 and type-I IFN synergize for IFN-gamma production by CD4 T cells, whereas neither are required for IFN-gamma production by CD8 T cells after Listeria monocytogenes infection.
Differentiation of Ag-specific T cells into IFN-gamma producers is essential for protective immunity to intracellular pathogens. In addition to stimulation through the TCR and costimulatory molecules, IFN-gamma production is thought to require other inflammatory cytokines. Two such inflammatory cytokines are IL-12 and type I IFN (IFN-I); both can play a role in priming naive T cells to produce IFN-gamma in vitro. However, their role in priming Ag-specific T cells for IFN-gamma production during experimental infection in vivo is less clear. In this study, we examine the requirements for IL-12 and IFN-I, either individually or in combination, for priming Ag-specific T cell IFN-gamma production after Listeria monocytogenes (Lm) infection. Surprisingly, neither individual nor combined defects in IL-12 or IFN-I signaling altered IFN-gamma production by Ag-specific CD8 T cells after Lm infection. In contrast, individual defects in either IL-12 or IFN-I signaling conferred partial ( approximately 50%) reductions, whereas combined deficiency in both IL-12 and IFN-I signaling conferred more dramatic (75-95%) reductions in IFN-gamma production by Ag-specific CD4 T cells. The additive effects of IL-12 and IFN-I signaling on IFN-gamma production by CD4 T cells were further demonstrated by adoptive transfer of transgenic IFN-IR(+/+) and IFN-IR(-/-) CD4 T cells into normal and IL-12-deficient mice, and infection with rLm. These results demonstrate an important dichotomy between the signals required for priming IFN-gamma production by CD4 and CD8 T cells in response to bacterial infection.


Secondary sexual characteristics in children with cerebral palsy and moderate to severe motor impairment: a cross-sectional survey.
To compare the development of secondary sexual characteristics in children with cerebral palsy (CP) of moderate to severe motor impairment to children in the general population and to relate their sexual maturation to a measure of their body fat. A multicenter, cross-sectional survey of 207 children who were 3 to 18 years of age and had CP of moderate to severe motor impairment (Gross Motor Functional Classification System [GMFCS] levels 3, 4, and 5) was conducted at 6 geographic sites; attempts were made to identify all eligible children through multiple methods and enroll them in the study. Trained research assistants performed anthropometric measurements, including subscapular skinfold thickness, determined GMFCS level, and assessed sexual maturation by Tanner stage. Secondary sexual characteristics were compared with the general population of children using cross-sectional surveys of the American Academy of Pediatrics Pediatric Research in Office Settings network and of the National Center for Health Statistics National Health and Nutrition Examination Survey (NHANES) III. Girls were classified as having begun puberty when they were at Tanner stage 2 or greater for pubic hair and breast development and to have completed puberty when they were at Tanner stage 4 or greater for pubic hair and breast development. Boys were classified as having begun puberty when they were at Tanner stage 2 or greater for pubic hair and genital development and to have completed puberty when they were at Tanner stage 4 or greater for pubic hair and genital development. The mean age (standard deviation) of subjects was 9.6 (4.6) years. Of the 207 subjects, 71% were white, 21% were black, and 8% were of other races; 59% were boys, and 41% were girls. Girls with CP (n = 84) entered puberty earlier than did boys with CP (n = 123). In contrast, girls with CP tended to complete puberty later than did boys with CP. Black boys and girls with CP (n = 43) entered puberty earlier than did white boys and girls with CP (n = 147). No difference between races was found in completion of puberty. Only for white children with CP were there a sufficient number of subjects for comparisons of sexual maturation to race-matched children in the general population, using data from the American Academy of Pediatrics Pediatric Research in Office Settings network and the NHANES III study. White girls with CP initiated pubic hair development (Tanner stage 2 or greater) earlier than in the general population, but the age of onset of breast development was similar to the general population, although the age distribution was different. A greater proportion of white girls with CP had early onset of breast development (Tanner stage 2 or greater), and a greater proportion had delayed onset of breast development than in the general population. White girls with CP completed breast development later than in the general population but not pubic hair development. For white boys ages 8 to 18 years with CP (n = 75), pubic hair and genital development both began earlier than in the general population, but genital development was completed later. The estimated median age of menarche for white girls with CP was 14.0 years, which was 1.3 years later (95% confidence interval: 0.7-2.3) than for the general population (estimated median age: 12.8 years; NHANES III). Relationships between sexual maturation and nutritional state, as assessed by subscapular skinfold thickness z score, were determined separately in white boys and in white girls with CP, between the ages of 8 and 18 years. For white girls with CP, more advanced sexual maturation was associated with more body fat, adjusting for age and GMFCS level (Spearman partial correlation: 0.41). In contrast, for white boys with CP, the opposite relationship pertained: more advanced sexual maturation was associated with less body fat (-0.29). The pattern of sexual maturation in children with CP of moderate to severe motor impairment differs from that of children in the general population. Puberty begins earlier but ends later in white children with CP, compared with white children in the general population. In addition, menarche occurs later in white girls with CP. More advanced sexual maturation was associated with more body fat in girls but less body fat in boys.


Chinese attitudes toward cleft lip and palate: effects of personal contact.
The purpose of this study was to investigate the effect of personal contact on the attitudes of individuals towards persons with cleft lip and palate (CLP) and the possible cultural differences in these attitudes for Chinese respondents living in Hong Kong. Chinese parent, teacher, and employer groups were administered a cleft lip and palate attitudinal questionnaire and the Scale of Attitudes Toward Disabled Persons inventory. Thirty-nine parents of children with CLP, 27 teachers of children with CLP, and 37 employers with no previous contact with individuals with CLP participated in the study. The results showed significant intergroup differences on several items involving beliefs concerning emotional health, social development, and employment-related barriers for individuals with CLP, and whether such individuals should seek nonmedical help to treat speech problems. Employers showed a comparatively less favorable attitude to persons with CLP than the two other groups. Parent, teacher, and employer groups in the Chinese community studied showed differences in their attitudes towards individuals with CLP. The findings suggest the need for further community health education to help develop more positive attitudes towards disabled persons in general, as well as programs targeted at reducing negative stereotyping of adults and children with CLP.


Medical education: how is change to come about?
The challenge to medical education as we enter the last decade of the century and face the next millenium is how to utilize the new knowledge of human learning to train medical students in applying the fruits of rapidly advancing science and technology to the moral imperative of fulfilling social needs. To bring about the reforms defined in the Edinburgh Declaration, adopted as globally applicable by the World Conference on Medical Education, intrinsic and extrinsic elements must act in synergy. The intrinsic elements are teachers, students and institutional frameworks; the extrinsic elements political will, administrative commitment and societal pressure. In the developing world, while there is much that medical schools themselves can do through intrinsic changes, their dependence on government support is so pervasive that such government support becomes an essential prerequisite for change. The creation of a cohesive organizational framework involving health and education ministries, the academic sector and professional bodies for a systematic and continuing study of medical education and for inducing and sustaining change are essential to facilitate the change process.


Hydrophobically Modified Abelmoschus esculentus Polysaccharide Based Nanoparticles and Applications: A Review.
Nanomaterials are indeed a nanoscale technology that deals with the creation, evaluation, fabrication, and utilization of systems at the nanometre scale by manipulating their size and shape. We consider natural polysaccharides such as promising polysaccharides, which are biodegradable, nontoxic, abundant, and inexpensive bio-polymeric precursors for preparing the materials of choice in various industries. The aim is to review different methods to produce hydrophobically modified Abelmoschus esculentus nanoparticles and study the evaluation processes of these nanoparticles as given in the literature. It proved the benefits of derivatives of gum by introducing different chemical groups. The chemical functionalization of gum mainly includes the esterification, etherification, and crosslinking reactions of the hydroxyl groups and contains a special fibre which takes sugar levels in the blood under control, providing a sugar quantity suitable for the bowels. Okra contains mucilage that helps remove poisonous chemicals and bad cholesterol, often overloads the liver. Recovering from psychological conditions, like depression, general weakness, and joint healthiness can be done with Okra. Someone additionally applied it for pulmonary inflammation, bowel irritation, and sore throat. Purgative properties okra possesses are beneficial for bowel purification. It is used to counteract the acids. Fibre okra contains a valuable nutrient for intestinal microorganisms and ensures proper intestine functionality. It also protects the mucosa of the digestive tract by covering them with an extra layer because of its alkaline nature. Nanotechnology has emerged as a critical component of pharmaceutics, with many applications in drug carriers of interest aimed at improving drug clinical outcomes such as cancer, diabetes mellitus, wound care management, atopic dermatitis, cosmeceutical, etc. Beneficial outcomes of this review are discussed briefly.


Influence of Percutaneous Drainage Surgery and the Interval to Perform Laparoscopic Cholecystectomy on Acute Cholecystitis through Genetic Algorithm-Based Contrast-Enhanced Ultrasound Imaging.
To discuss the optimal interval time between genetic algorithm-based ultrasound imaging-guided percutaneous drainage surgery (PTGD) and laparoscopic cholecystectomy (LC), 64 cholecystitis patients were selected as the research objects and evenly divided into experimental group (intelligent algorithm was adopted to recognize patients' ultrasonic images) and control group (professional doctors carried out diagnosis). 92 acute cholecystitis patients undergoing PTGD were divided into three groups. 30 out of the 92 patients received LC within 2 months and were defined as the early group. 32 were performed with LC within 2 to 4 months and were defined as the metaphase group. 28 underwent LC over 4 months and were defined as the late-stage group. The average operation time, the transition from LC to laparotomy, the average postoperative hospital stay, and the incidence of complications of the three groups were compared. The results revealed that the comparison of the diagnostic accuracy and comprehensive effectiveness between experimental group and control group demonstrated that the differences were statistically significant (P < 0.05). When the optimal interval of implementing LC after PTGD was realized, the corresponding values of the early group were 88.5 minutes, 16.67%, 8.13 days, and 13.75%. Those of the metaphase group were 49.91 minutes, 3.13%, 4.97 days, and 9.52%. Those of the late stage group were 68.78 minutes, 10.71%, 7.09 days, and 11.96%. To sum up, the diagnostic accuracy and comprehensive effectiveness of intelligent algorithm were higher than those of conventional ultrasound, and the optimal interval time of implementing LC after PTGD was 2 to 4 months.


Real-time 3D single-molecule localization using experimental point spread functions.
We present a real-time fitter for 3D single-molecule localization microscopy using experimental point spread functions (PSFs) that achieves minimal uncertainty in 3D on any microscope and is compatible with any PSF engineering approach. We used this method to image cellular structures and attained unprecedented image quality for astigmatic PSFs. The fitter compensates for most optical aberrations and makes accurate 3D super-resolution microscopy broadly accessible, even on standard microscopes without dedicated 3D optics.


Prognostic Value of Axillary Lymph Node Texture Parameters Measured by Pretreatment 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Locally Advanced Breast Cancer with Neoadjuvant Chemotherapy.
This study investigated the prognostic value of axillary lymph node (ALN) heterogeneity texture features through 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in patients with locally advanced breast cancer (LABC). We retrospectively analyzed 158 LABC patients with FDG-avid, pathology-proven, metastatic ALN who underwent neoadjuvant chemotherapy (NAC) and curative surgery. Tumor and ALN texture parameters were extracted from pretreatment 18F-FDG PET/CT using Chang-Gung Image Texture Analysis software. The least absolute shrinkage and selection operator regression was performed to select the most significant predictive texture parameters. The predictive impact of texture parameters was evaluated for both progression-free survival and pathologic NAC response. The median follow-up period of 36.8 months and progression of disease (PD) was observed in 36 patients. In the univariate analysis, ALN textures (minimum standardized uptake value (SUV) (p = 0.026), SUV skewness (p = 0.038), SUV bias-corrected Kurtosis (p = 0.034), total lesion glycolysis (p = 0.011)), tumor textures (low-intensity size zone emphasis (p = 0.045), minimum SUV (p = 0.047), and homogeneity (p = 0.041)) were significant texture predictors. On the Cox regression analysis, ALN SUV skewness was an independent texture predictor of PD (p = 0.016, hazard ratio 2.3, 95% confidence interval 1.16-4.58). ALN texture feature from pretreatment 18F-FDG PET/CT is useful for the prediction of LABC progression.


Diabetic Retinopathy: From Animal Models to Cellular Signaling.
Diabetic retinopathy (DR) is an ocular complication of diabetes mellitus (DM), a metabolic disorder characterized by elevation in blood glucose level. The pathogenesis of DR includes vascular, neuronal, and inflammatory components leading to activation of complex cellular molecular signaling. If untreated, the disease can culminate in vision loss that eventually leads to blindness. Animal models mimicking different aspects of DM complications have been developed to study the development and progression of DR. Despite the significant contribution of the developed DR models to discovering the mechanisms of DR and the recent achievements in the research field, the sequence of cellular events in diabetic retinas is still under investigation. Partially, this is due to the complexity of molecular mechanisms, although the lack of availability of models that adequately mimic all the neurovascular pathobiological features observed in patients has also contributed to the delay in determining a precise molecular trigger. In this review, we provide an update on the status of animal models of DR to help investigators choose an appropriate system to validate their hypothesis. We also discuss the key cellular and physiological events of DR in these models.


How Research on Charitable Giving Can Inform Strategies to Promote Human Milk Donations to Milk Banks.
Many hospitalized preterm infants do not exclusively receive mother's own milk, so milk from another mother may be sought. Previous research indicated that just 1% of US women who express breast milk actually donate it for another family. Therefore, strategies to boost donation rates should be identified. We draw upon the experimental literature on charitable giving of monetary donations to offer 6 strategies to promote breast milk donations to milk banks in North America. These strategies include (1) highlighting a potential identifiable recipient of donated breast milk as opposed to highlighting groups of potential recipients; (2) emphasizing similarities between the potential donor and potential beneficiaries; (3) emphasizing similarities between the potential donor and previous donors; (4) using negative arousal to promote donations; (5) emphasizing the self-interest of those asking for breast milk donations; and (6) highlighting the specific effect of breast milk donations. Potential limitations of these strategies are discussed.


N-Acetylglucosamine Metabolism Promotes Survival of Candida albicans in the Phagosome.
Phagocytosis by innate immune cells is one of the most effective barriers against the multiplication and dissemination of microbes within the mammalian host. Candida albicans, a pathogenic yeast, has robust mechanisms that allow survival upon macrophage phagocytosis. C. albicans survives in part because it can utilize the alternative carbon sources available in the phagosome, including carboxylic acids and amino acids. Furthermore, metabolism of these compounds raises the pH of the extracellular environment, which combats the acidification and maturation of the phagolysosome. In this study, we demonstrate that metabolism by C. albicans of an additional carbon source, N-acetylglucosamine (GlcNAc), facilitates neutralization of the phagosome by a novel mechanism. Catabolism of GlcNAc raised the ambient pH through release of ammonia, which is distinct from growth on carboxylic acids but similar to growth on amino acids. However, the effect of GlcNAc metabolism on pH was genetically distinct from the neutralization induced by catabolism of amino acids, as mutation of STP2 or ATO5 did not impair the effects of GlcNAc. In contrast, mutants lacking the dedicated GlcNAc transporter gene NGT1 or the enzymes responsible for catabolism of GlcNAc were defective in altering the pH of the phagosome. This correlated with reduced survival following phagocytosis and decreased ability to damage macrophages. Thus, GlcNAc metabolism represents the third genetically independent mechanism that C. albicans utilizes to combat the rapid acidification of the phagolysosome, allowing for cells to escape and propagate infection. IMPORTANCECandida albicans is the most important medically relevant fungal pathogen, with disseminated candidiasis being the fourth most common hospital-associated bloodstream infection. Macrophages and neutrophils are innate immune cells that play a key role in host defense by phagocytosing and destroying C. albicans cells. To survive this attack by macrophages, C. albicans generates energy by utilizing alternative carbon sources that are available in the phagosome. Interestingly, metabolism of amino acids and carboxylic acids by C. albicans raises the pH of the phagosome and thereby blocks the acidification of the phagosome, which is needed to initiate antimicrobial attack. In this work, we demonstrate that metabolism of a third type of carbon source, the amino sugar GlcNAc, also induces pH neutralization and survival of C. albicans upon phagocytosis. This mechanism is genetically and physiologically distinct from the previously described mechanisms of pH neutralization, indicating that the robust metabolic plasticity of C. albicans ensures survival upon macrophage phagocytosis.


A double blind comparative multicentre study of remoxipride and haloperidol in schizophrenia.
Seventy-two patients fulfilling the DSM-III criteria for schizophrenia and schizophreniform psychosis were admitted to a multicentre, double-blind controlled study to evaluate the efficacy and safety of remoxipride in comparison to haloperidol. The mean daily dose of remoxipride at the end of treatment was 353 mg and of haloperidol, 11 mg. Patients were assessed each week on the Brief Psychiatric Rating Scale (BPRS), the Clinical Global Impression (CGI) and the symptoms checklist. No significant differences in efficacy were found between the two treatments. The median total BPRS score in the remoxipride group was 25 at start of active treatment and 17 at the last valid rating (n = 31). For the haloperidol group the corresponding figures were 24 and 15 (n = 29). According to the CGI, 40% of remoxipride patients and 50% of haloperidol patients were much or very much improved. Treatment-emergent extrapyramidal symptoms, such as akathisia and rigidity, occurred significantly more frequently, and were more severe during treatment with haloperidol than with remoxipride (p = 0.012 and 0.024, respectively). Haloperidol-treated patients reported significantly more drowsiness and increased sleep during treatment (p = 0.026 and 0.012, respectively). No statistically significant differences were seen in endocrine or autonomic symptoms. Remoxipride seemed to be as effective as haloperidol, had a lower frequency of side effects, and was used safely in the dose range 150-600 mg/day.


A Delphi survey to determine a definition and description of hyperacusis by clinician consensus.
There is currently no singularly accepted definition of hyperacusis. The aim of this study was to determine a definition and description of hyperacusis by clinician consensus. A three-round Delphi survey involving hearing healthcare professionals built towards clinical consensus on a definition of hyperacusis. Round 1 involved three open-ended questions about hyperacusis. Seventy-nine statements were generated on descriptions, impact, sounds, and potential features of hyperacusis. Agreement on the relevance of each statement to defining or describing hyperacusis was then measured in Rounds 2 and 3. General consensus was defined a priori as ≥70% agreement, or ≥90 for clinical decision making. Forty-five hearing healthcare professionals were recruited to take part in this study. Forty-one completed Round 1, 36 completed Round 2, and 33 completed Round 3. Consensus was reached on 42/79 statements. From these a consensus definition includes "A reduced tolerance to sound(s) that are perceived as normal to the majority of the population or were perceived as normal to the person before their onset of hyperacusis". A consensus description of hyperacusis was also determined. This consensus definition of hyperacusis will help to determine the scope of clinical practice guidelines and influence needed research on hyperacusis.


Evaluating and treating exercise-related menstrual irregularities.
Menstrual abnormalities, from a few skipped periods to a complete absence of menses, are extremely common in both athletic and nonathletic adolescents and women in their early 20s. Exercise-related menstrual abnormality is linked with hypothalamic pituitary axis dysfunction and is a diagnosis of exclusion. In athletes, treatment of secondary menstrual abnormalities and associated health concerns, such as bone density, may include medication and restriction from activity.


[Human microsporidiosis].
This review shows the Microsporidia as unicellular protozoa strictly intracellular eukaryotic parasites of animals and humans. These study concerns life cycles, cytology, host-parasite relationships in animal models experimentally infected with microsporidia from human feces, demonstrating the host-inespecificity and visceral dissemination with histopathological studies in digestive, tract, kidney, liver, spleen, brain, heart, pancreas, thyroid, suprarenal glands. It is presented the microsporidiosis in Venezuela in immunocompetent patients and immunodeficients HIV+, with diarrheic syndromes with keratoconjuntivitis microsporidial punctata diffuse and with disseminated microsporidia in urine, tracheobronchial sputum, nasal and pharyngeal exudates. Also we have found the microsporidia in river and lake waters and in animals relationed with the man: dogs, cats, pigs, monkeys, donkeys, guts. The patients are treated specially with Albendazole and also with Trimethoprim-Sulphametoxazol for the children until two years of age. We use as laboratory diagnosis the technique of Kinyoun stain, in support of the acid resistance property of these parasites, and also the Chromotrope staining. Our recommendations for a proper identification of the Microspora species, should be done with Electron Microscopy and the TCR reaction.


Review article: Barrett's oesophagus and associated adenocarcinoma--a UK perspective.
In the UK and across the Western world there has been a rapid increase in oesophageal adenocarcinoma, such that this cancer is now more common than squamous cell carcinoma. The 5-year mortality from oesophageal adenocarcinoma is >80% and therefore there has been increasing interest in the pre-malignant condition Barrett's oesophagus. Barrett's oesophagus is defined by a visible columnar-lined segment with histopathological evidence of a glandular epithelium, which typically contains intestinal metaplasia. Once Barrett's oesophagus is diagnosed, most centres in the UK offer endoscopic surveillance with the aim to detect early, curable lesions. Surveillance in its current form is cumbersome and expensive, and new endoscopic and molecular developments are hoped to improve the yield of such procedures. The current treatments are symptomatic control of reflux symptoms, with more definitive treatments usually reserved for patients with at least high-grade dysplasia. There is interest in chemoprevention strategies, including proton-pump inhibitors, cyclo-oxygenase-2 inhibitors and aspirin, but to date none of these have proven effective. Treatment options for high-grade dysplasia include surgery, endoscopic mucosal resection (in the context of a visible lesion) and photodynamic therapy. Comparative studies between various geographical regions, as the predominant histopathological subtypes of oesophageal cancer change, may give us some clues about the pathogenesis of Barrett's adenocarcinoma.


Thyroid surgery for elderly patients: are they at increased operative risks?
An increasing elderly population, a rising incidence of differentiated thyroid carcinoma (DTC), and a rising incidence of benign nodular disease with age are all contributing to a rise in thyroid operations for the elderly. Literature review on the outcome and safety of thyroid surgery in elderly patients has been filled with conflicting results and this subject remains controversial. Although most single-institution studies conducted by high-volume surgeons did not find significant differences of complication rates in elderly when compared with younger cohorts, they often lacked the power necessary to identify subtle differences and suffered from various selection and referral biases. Recent evidence from large population-based studies concluded that thyroid surgery in the elderly was associated with higher complication rates. One of the major contributing factors for the increased complication rate was because most elderly patients suffered from many preexisting comorbidities. Therefore, elderly patients who have abnormal thyroid findings should complete a thorough preoperative workup and better postoperative care after undergoing any thyroid surgery. Furthermore, these high-risk patients would benefit if they could be referred to high-volume, specialized surgical units early. In this systemic review, we aimed to evaluate different issues and controversies in thyroidectomy for elderly patients.


Very late drug-eluting stent thrombosis in the perioperative period of endoscopic choledocholithotomy.
Very late stent thrombosis is an uncommon but life-threatening complication after drug-eluting stent implantation in patients with coronary artery disease. Discontinuation of antiplatelet therapy is reported to be the most powerful predictor of stent thrombosis. This article reports on a case of very late stent thrombosis 54 months after implantation of a drug-eluting stent, in a patient who discontinued dual antiplatelet therapy only 11 days before endoscopic choledocholithotomy, and argues in favour of continuing aspirin therapy perioperatively in surgical patients with low bleeding risk, even if dual antiplatelet therapy has been followed more than 12 months after stent implantation.


Prognostic significance of nuclear DNA content in small cell carcinoma of the lung.
The relationship between the nuclear DNA histogram patterns of tumor cells obtained by brushing via bronchoscopy and the survival time of 39 patients with small cell carcinoma of the lung was investigated. The brushing smears were stained by a modified Feulgen method. The nuclear DNA content was measured at 550 nm using a microspectrophotometer. The DNA histogram pattern was classified into type I, which contained a higher proportion of G0G1-phase cells, and type II, which contained a higher proportion of S, G2M-phase cells. The median survival times for the patients with limited disease of type I, type II and the patients with extensive disease of type I, type II were 17.2 months, 10.2 months, 10.0 months, and 5.6 months, respectively. Patients with limited disease of type I had a significantly longer survival time than patients with limited disease of type II. A distinct correlation was found between the histogram pattern and the survival of the patients. These results indicated that the nuclear DNA histogram pattern may be an indicator to allow speculation as to the prognosis of patients with small cell carcinoma of the lung.


N-acetylcysteine attenuates oxidative burst by neutrophils in response to ergometer rowing with no effect on pulmonary gas exchange.
This study evaluated whether the reduction of the neutrophil oxidative burst by N-acetylcysteine improves pulmonary gas exchange during a six minute maximal ergometer row. Healthy trained oarsmen were double-blinded randomized to either N-acetylcysteine (6 g daily for three days) or placebo groups. As determined by the relative changes of the zymosan-stimulated luminol-enhanced chemiluminescence response, N-acetylcysteine suppressed the exercise-induced enhanced neutrophil oxidative burst response to rowing (-7 +/- 6% vs. 17 +/- 8%; P < 0.05). This was the case although the concentration of neutrophils remained similarly elevated above the pre-exercise level in both trials (to 5.4+/-0.5 vs. 5.9+/-0.6 x 10(9) cells x l(-1), respectively, P>0.05). In the placebo and N-acetylcysteine groups, pulmonary ventilation increased and the arterial CO2 partial pressure decreased to the same extent during exercise. Also, at the end of exercise the arterial O2 partial pressure (77 1 vs. 78+/-1 mmHg), haemoglobin O2 saturation (92 +/- 1% vs. 93 +/- 1%) and O2 uptake (5.0 +/- 0.2 vs. 4.9 +/- 0.21 x min(-1)) were not significantly affected by N-acetylcysteine. Equally, two hours after exercise, the pulmonary diffusion capacity was reduced by 7 +/- 2% below the pre-exercise with no significant influence of N-acetylcysteine. We conclude that the neutrophil oxidative burst to exercise does not influence pulmonary gas exchange during and after maximal rowing.


[Research on hepatitis C virus entry inhibitor].
Hepatitis c virus (HCV) infection has become one of the global public health problem,while there is no vaccine to prevent HCV infection, the so-called "cocktail" therapy that use a combination of drugs targeting multiple steps in the HCV infection cycle could achieve better curative effect. the process of HCV entering into host cell is the important step of drug intervention, in which HCV envelope protein El and E2, Host cell factors including Heparan sulfate(HS), CD81, scavenger receptor class B type I (SR-BI), Occludin (OCLD), Claudin (CLDN), low densitity lipoprotein receptor (LDLR), dendritic cell-specific ICAM-3-grabbing nonintegrin (DC-SIGN), Liver/lymph node specific ICAM-3-grabbing integrin(L-SIGN), trans- ferrin receptor 1 (TfR1) and so on play a important role. The virus and the host factors can be used as targets of hcv entry inhibitors many studies have shown that as novel and promising compounds, HCV entry inhibitors combinating with other drugs can be more effective in the treatment of HCV, this paper have re- viewed targets and inhibitors of HCV enterring into host cell since 1990s.


Effectiveness of virtual reality exposure in the treatment of arachnophobia using 3D games.
Buying or creating a virtual reality (VR) software is very costly. A less expensive alternative could be to modify already existing 3D computer games. The goal of this study is to assess the effectiveness of in virtuo exposure in the treatment of arachnophobia using modified 3D games. Participants were 10 women and 1 man. Virtual worlds were created using the game editor of a 3D computer game (Half-Life), modified to offer graduals hierarchies of fearful stimuli (spiders). Analyses revealed significant improvement between pre and post results on the behavioral avoidance test, the Spider Beliefs Questionnaire, and perceived self-efficacy. These promising results suggest that therapy using virtual reality exposure via a modified computer game is useful in the treatment of arachnophobia.


Application of Biobased Solvents in Asymmetric Catalysis.
The necessity of more sustainable conditions that follow the twelve principles of Green Chemistry have pushed researchers to the development of novel reagents, catalysts and solvents for greener asymmetric methodologies. Solvents are in general a fundamental part for developing organic processes, as well as for the separation and purification of the reaction products. By this reason, in the last years, the application of the so-called green solvents has emerged as a useful alternative to the classical organic solvents. These solvents must present some properties, such as a low vapor pressure and toxicity, high boiling point and biodegradability, and must be obtained from renewable sources. In the present revision, the recent application of these biobased solvents in the synthesis of optically active compounds employing different catalytic methodologies, including biocatalysis, organocatalysis and metal catalysis, will be analyzed to provide a novel tool for carrying out more ecofriendly organic processes.


Controlling the directional emission of light by periodic arrays of heterostructured semiconductor nanowires.
We demonstrate experimentally the directional emission of light by InAsP segments embedded in InP nanowires. The nanowires are arranged in a periodic array, forming a 2D photonic crystal slab. The directionality of the emission is interpreted in terms of the preferential decay of the photoexcited nanowires and the InAsP segments into Bloch modes of the periodic structure. By simulating the emission of arrays of nanowires with the emitting segments located at different heights, we conclude that the position of this active region strongly influences the directionality and efficiency of the emission. Our results will help to improve the design of nanowire based LEDs and single photon sources.


Community-based integrated approach to changing women's family planning behaviour in Pakistan, 2014-2016.
Setting: Karachi, Pakistan. Objective: To assess the effectiveness of a community-based integrated approach in changing women's behaviour regarding contraceptive use. Design: The Sukh Initiative is a multipronged approach with door-to-door services using community health workers to provide quality family planning/reproductive health services at both public and private facilities and a 24/7 family planning helpline service that provides youth skill-based education. Methods: Retrospective pre- and post-intervention data using samples of 5140 and 3810 women, respectively. Results: The contraceptive prevalence rate increased by 10.7%, from 42.3% at baseline to 53.0% mid-intervention, with an increase in use of modern contraceptive methods of 9.2%. A significant association was found between door-to-door counselling and the use of contraceptive methods (OR 3.4, 95%CL 2.9-4.1) and access to public and private facilities for modern contraceptives (OR 2.4, 95%CL 2.0-3.0). However, support group meetings and 24/7 helpline use did not show any association with use of contraceptive method. Conclusion: The study helped to increase access to and choice of family planning services through a community-based approach that successfully reduced unmet needs and improved continuity in contraceptive use.


Surface morphology of Au-free grown nanowires after native oxide removal.
Using scanning tunneling microscopy, we evaluate the surface structure and morphology down to the atomic scale for micrometers along Au-free grown InAs nanowires (NWs) free from native oxide. We find that removal of the native oxide (which covers the NWs upon exposure to the ambient air) using atomic hydrogen does not alter the underlying step structure. Imaging with sub-nanometer resolution along the NWs, we find an extremely low tapering (diameter change along the NW) of 1.7 ± 0.5 Åμm(-1). A surface morphology with monolayer high islands, whose shape was influenced by stacking faults, was found to cover the NWs and was attributed to the decomposed native oxide. The appearance of point defects in the form of As-vacancies at the surface is analyzed and we set limits to the amount of carbon impurities in the NWs.


Learning a Metric for Multimodal Medical Image Registration without Supervision Based on Cycle Constraints.
Deep learning based medical image registration remains very difficult and often fails to improve over its classical counterparts where comprehensive supervision is not available, in particular for large transformations-including rigid alignment. The use of unsupervised, metric-based registration networks has become popular, but so far no universally applicable similarity metric is available for multimodal medical registration, requiring a trade-off between local contrast-invariant edge features or more global statistical metrics. In this work, we aim to improve over the use of handcrafted metric-based losses. We propose to use synthetic three-way (triangular) cycles that for each pair of images comprise two multimodal transformations to be estimated and one known synthetic monomodal transform. Additionally, we present a robust method for estimating large rigid transformations that is differentiable in end-to-end learning. By minimising the cycle discrepancy and adapting the synthetic transformation to be close to the real geometric difference of the image pairs during training, we successfully tackle intra-patient abdominal CT-MRI registration and reach performance on par with state-of-the-art metric-supervision and classic methods. Cyclic constraints enable the learning of cross-modality features that excel at accurate anatomical alignment of abdominal CT and MRI scans.


Federal programs to reimburse the public for environmental and occupational exposures.
Since the mid-1980's there has been growing public concern about possible health effects associated with radiation exposures of veterans and atomic weapons workers. These concerns have led to a series of Congressional actions that have resulted in legislation creating three compensation programs that are intended to compensate individuals whose radiation exposures may be considered a causative agent for specified health effects.


Rationally designed structure of mesoporous carbon hollow microspheres to acquire excellent microwave absorption performance.
In this study, we used a novel and facile hard-template etching method to manufacture mesoporous carbon hollow microspheres (MCHMs). We prove that the dielectric ability and microwave absorption of MCHMs can be adjusted by structural characteristics. When the average particle size of MCHMs is 452 nm, the paraffin composite material mixed with 10 wt% MCHMs can achieve a maximum reflection loss value of -51 dB with a thickness of 4.0 mm at 7.59 GHz. When the average particle size of MCHMs is 425 nm, the effective absorption bandwidth of the paraffin composite material mixed with 10 wt% MCHMs can achieve a broad bandwidth of 7.14 GHz with a thickness of 2.5 mm. Compared with other microwave absorbers, MCHMs possess high microwave absorption capacity and broad microwave absorption bandwidth with as low as a 10 wt% filler ratio. This excellent microwave absorption performance is due to the internal cavity and the mesoporous shell of MCHMs. By rationally designing the structure of MCHMs, excellent microwave absorption performance can be acquired. Meanwhile, this design concept based on a rational design of spherical structure can be extended to other spherical absorbers.


Clusters of Comorbidities in the Short-Term Prognosis of Acute Heart Failure among Elderly Patients: A Retrospective Cohort Study.
Background and Objectives: Elderly patients affected by acute heart failure (AHF) often show different patterns of comorbidities. In this paper, we aimed to evaluate how chronic comorbidities cluster and which pattern of comorbidities is more strongly related to in-hospital death in AHF. Materials and Methods: All patients admitted for AHF to an Internal Medicine Department (01/2015−01/2019) were retrospectively evaluated; the main outcome of this study was in-hospital death during an admission for AHF; age, sex, the Charlson comorbidity index (CCI), and 17 different chronic pathologies were investigated; the association between the comorbidities was studied with Pearson's bivariate test, considering a level of p ≤ 0.10 significant, and considering p < 0.05 strongly significant. Thus, we identified the clusters of comorbidities associated with the main outcome and tested the CCI and each cluster against in-hospital death with logistic regression analysis, assessing the accuracy of the prediction with ROC curve analysis. Results: A total of 459 consecutive patients (age: 83.9 ± 8.02 years; males: 56.6%). A total of 55 (12%) subjects reached the main outcome; the CCI and 16 clusters of comorbidities emerged as being associated with in-hospital death from AHF. Of these, CCI and six clusters showed an accurate prediction of in-hospital death. Conclusions: Both the CCI and specific clusters of comorbidities are associated with in-hospital death from AHF among elderly patients. Specific phenotypes show a greater association with a worse short-term prognosis than a more generic scale, such as the CCI.


Morphometric studies on the rat renal papilla of resistant and sensitive strains in partial nephrectomy salt hypertension.
The renomedullary interstitial cell (RIC) was studied morphometrically in the partial nephrectomy-salt (Chanutin-Ferris) model of hypertension. The RIC were compared in four strains of rat, two of them being resistant to the induction of this form of hypertension and two of them being sensitive. The Dahl salt-resistant (R/JR) rat was compared to a commercial Sprague-Dawley (SD) strain, and a Wistar derived strain discovered in Belgrade by Susic and Kentera (WB) was compared to a commercial Wistar strain (W). In both studies, resistance and sensitivity correlated well with the state of the RIC before the experimental procedure, the resistant strain having more numerous and better granulated RIC than the sensitive strain. It may therefore be possible to predict salt-resistance or sensitivity in rats by morphological examination of the RIC.


A comparative study of carcass characteristics and meat quality in genetic resources Pekin ducks and commercial crossbreds.
The study was aimed to compare carcass traits, physicochemical and textural properties of meat in two different genotypes of Pekin ducks with regard to sex effect. The study involved 120 Pekin ducks - 30 males and 30 females of strain P33 (Polish native Pekin ducks) and 30 males and 30 females of Star 53 HY (commercial hybrid Pekin ducks). At 49 d of age, 48 birds (12 males and 12 females of each genotype) were selected for dissection. After the dissection, meat samples were collected to determine meat quality traits. The studied Pekin ducks of different genotype showed significant differences in body weight, carcass weight, dressing percentage, as well as percentages of breast muscles, skin with subcutaneous fat, abdominal fat, neck, and remainders of eviscerated carcass with neck. Duck genotype had an effect on the content of crude protein, crude fat, Na, K, P, Zn, pH24, electric conductivity (EC24), cooking loss, L*, a*, most textural traits of breast muscle, and also Na, Mg and Fe content, EC24, drip loss, cooking loss and L*, a* and b* colour coordinates of leg muscles. Regardless of genetic origin, males exhibited higher BW, carcass weight and carcass neck percentage, as well as lower redness, hardness, chewiness and gumminess of breast muscle compared to females. The genotype sex interaction was significant for the crude fat content and cooking loss of breast muscle, and for the yellowness of leg muscle. Star 53 HY ducks are more suited for broiler production due to their higher body weight and dressing percentage. Their breast and leg meat are characterized by more beneficial chemical composition but has poorer sensory and textural properties compared to the meat of P33 ducks.


Bucillamine-induced pemphigus vulgaris in a patient with rheumatoid arthritis and polymyositis overlap syndrome.
Bucillamine is a disease modifying anti-rheumatic drug, structurally similar to D-penicillamine. Although D-penicillamine-induced pemphigus has been not infrequently demonstrated, pemphigus associated with bucillamine was rarely reported. We describe a patient complicating pemphigus vulgaris after bucillamine treatment in rheumatoid arthritis (RA) and polymyositis (PM) overlap syndrome. PM and RA overlap syndrome was diagnosed three years ago and bucillamine was administrated for 20 months. Skin lesions including erythematous flaccid blisters on her chest, axillae, and back were occurred and were compatible with pemphigus vulgaris by typical pathology. Withdrawal from bucillamine and prednisolone treatment made rapid improvement of pemphigus lesions.


Pulmonary persistence of Haemophilus somnus in the presence of specific antibody.
Chronic experimental Haemophilus somnus pneumonia was produced in five 8- to 12-week-old calves to investigate host-parasite relationships in the respiratory tract. Calves were depressed and pyrexic and coughed intermittently for 3 days and then recovered except for sporadic coughing. Bacteria persisted in the lung for 6 to 10 weeks or more. Immunoglobulin G1 (IgG1), IgG2, and IgM but no IgA antibodies specific for H. somnus were detected in serum. Bronchoalveolar lavage samples contained detectable IgG1, IgG2, IgM, and IgA antibodies specific for H. somnus throughout most of the experiment. The kinetics of the isotypic antibody response against H. somnus in serum and bronchoalveolar lavage fluids differed, suggesting that both local and systemic antibody responses had occurred. Persistence of pulmonary infection for 10 weeks or more in the presence of antibody may be due to an inappropriate distribution of isotypes, toxicity of H. somnus for bovine macrophages, and perhaps other factors. Three of the calves were challenged with a 10-fold-higher dose of H. somnus at 10 weeks after the original inoculation. Immunity against H. somnus was indicated by the rapid clearance of bacteria from the lungs and the presence of minimal pneumonia at necropsy 3 days after bacterial challenge.


Is prevention the best treatment? CMV after lung transplantation.
Cytomegalovirus (CMV) is the most prevalent opportunistic infection that occurs in lung-transplant recipients. In addition to its direct morbidity, multiple studies have demonstrated that CMV, in particular CMV pneumonia, is associated with an increased risk for chronic graft dysfunction manifested as bronchiolitis obliterans syndrome (BOS) and worse posttransplant survival. Therefore, prevention of CMV remains an important goal to improve long-term lung-transplant outcomes. Although centers often employed 3 months of prophylaxis in at-risk patients after lung transplantation, a significant proportion of patients still developed infection or disease after the discontinuation of prophylaxis, highlighting the need for more effective approaches to CMV prevention. A number of early single-center reports suggested benefit to extending prophylaxis to longer durations, but concerns regarding cost, late-onset CMV disease, viral resistance and bone marrow toxicity limited enthusiasm for longer durations. However, several recent studies including a multicenter, prospective, randomized, double-blinded clinical trial have demonstrated significant benefits to extending CMV prophylaxis beyond 3 months. Although some areas of controversy remain, the clinical implications of these recent studies suggest that extending prophylaxis with valganciclovir up to 12 months is clearly beneficial for CMV prevention after lung transplantation.


Industrial-scale fabrication of an osteogenic and antibacterial PLA/silver-loaded calcium phosphate composite with significantly reduced cytotoxicity.
In this study, we report an industrial-scale fabrication method of a multifunctional polymer composite as a scaffold material for bone tissue engineering. This study successfully demonstrated the potential of applying industrial polymer processing technologies to produce specially functionalized tissue engineering scaffolds. With the inclusion of a newly synthesized multifunctional additive, silver-doped-calcium phosphate (silver-CaP), the composite material exhibited excellent osteogenic inducibility of human adipose-derived stem cells (hASC) and satisfactory antibacterial efficacy against Escherichia coli and Staphylococcus aureus. Also, relative to previously reported methods of direct loading silver particles into polymeric materials, our composite exhibited significantly reduced silver associated cytotoxicity. The enhanced biocompatibility could be a significant advantage for materials to be used for regenerative medicine applications where clinical safety is a major consideration. The impact of different silver loading methodologies on hASC' osteogenic differentiation was also studied. Overall, the results of this study indicate a promising alternative approach to produce multifunctional scaffolds at industrial-scale with higher throughput, lower cost, and enhanced reproducibility. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 900-910, 2019.


Periodic Structural Defects in Graphene Sheets Engineered via Electron Irradiation.
Artificially-induced defects in the lattice of graphene are a powerful tool for engineering the properties of the crystal, especially if organized in highly-ordered structures such as periodic arrays. A method to deterministically induce defects in graphene is to irradiate the crystal with low-energy (<20 keV) electrons delivered by a scanning electron microscope. However, the nanometric precision granted by the focused beam can be hindered by the pattern irradiation itself due to the small lateral separation among the elements, which can prevent the generation of sharp features. An accurate analysis of the achievable resolution is thus essential for practical applications. To this end, we investigated patterns generated by low-energy electron irradiation combining atomic force microscopy and micro-Raman spectroscopy measurements. We proved that it is possible to create well-defined periodic patterns with precision of a few tens of nanometers. We found that the defected lines are influenced by electrons back-scattered by the substrate, which limit the achievable resolution. We provided a model that takes into account such substrate effects. The findings of our study allow the design and easily accessible fabrication of graphene devices featuring complex defect engineering, with a remarkable impact on technologies exploiting the increased surface reactivity.


Urine Output Assessment in Acute Kidney Injury: The Cheapest and Most Impactful Biomarker.
Acute kidney injury (AKI) is independently associated with morbidity and mortality in critically ill neonates, children, adolescents, and young adults. AKI occurs commonly in this population, and the vast majority of published studies utilize only a serum creatinine based criteria for AKI diagnosis and staging. While urine output criteria have been a part of all AKI systematic and multidimensional AKI definitions for the past 15 years, oliguria based on these definitions is difficult to extract from the electronic health record. This manuscript reviews the published data regarding the impact of oliguria on patient outcomes, and the contribution of oliguria to % fluid overload and resultant changes in serum creatinine based epidemiology. The aim of this manuscript is to demonstrate that oliguria is an incredibly valuable biomarker for the management of patients with, or at-risk for, AKI.


[New aspects of antineutrophil cytoplasmic antibody (ANCA) diagnosis in vasculitis].
Anti-Neutrophil Cytoplasmic Antibodies (ANCA) are a heterogenous group of autoantibodies with a broad spectrum of clinically associated diseases. The diagnostic value is established of Proteinase 3 (PR3)-ANCA for Wegener's granulomatosis (WG) as well as Myeloperoxidase (MPO)-ANCA for microscopic polyangiitis (MPA). Within the last 20 years these antibodies were subject of intensive studies and a growing body of evidence arose for a distinct role of ANCA in the pathogenesis of the ANCA associated vasculitides WG and MPA. Our current concept of whether ANCA directly or indirectly contribute to vascular damage (ANCA-Cytokine-Sequence-Theory) was mainly developed from in vitro studies. It is plausible and it is supported by data from clinical investigations as well as animal models. Nevertheless our knowledge of the etiological and pathogenetic pathways remains incomplete.


Mid-point transverse process to pleura block for surgical anaesthesia.
The use of ultrasound in regional anaesthesia has expanded our understanding of regional anaesthesia techniques and allowed for the development of novel strategies to achieve blockade of the trunk. Several alternatives to paravertebral block have recently been proposed, but none of these new techniques have yet been shown to provide surgical anaesthesia equivalent to a paravertebral block. This case report describes the successful use of the mid-point transverse process to pleura (MTP) block as the sole anaesthetic technique for a patient undergoing breast surgery.


The expression of Indoleamine 2, 3-dioxygenase (IDO) is reduced in granulomas from BCG vaccinated cattle compared to granulomas from unvaccinated controls after experimental challenge with Mycobacterium bovis.
Bovine tuberculosis (bTB), mainly caused by Mycobacterium bovis (M. bovis), is a major economic disease of livestock worldwide. Vaccination is considered as a potentially sustainable adjunct to the current control strategy. Cattle vaccination with the live attenuated M. bovis bacillus Calmette-Guerin (BCG) confers variable protection; the reasons for this variability are not understood. Indoleamine 2, 3-dioxygenase (IDO), through the catalysis of tryptophan, is thought to have an immunoregulatory role in the immune response to Mycobacterium tuberculosis (M. tuberculosis). In this work, we used immunohistochemistry and digital image analysis to evaluate the presence of IDO in granulomas at different stages of development in cattle that had been BCG-vaccinated or not and then challenged with M. bovis. Our results show that the expression of IDO in granulomas from non-vaccinated M. bovis challenged animals is higher than in granulomas from BCG-vaccinated M. bovis challenged animals. Thus, it is possible that vaccination with BCG prevents the induction of what are thought to be host immunosuppressive pathways by M. bovis, which contribute to pathology during the disease.


COVID-19 transmission in group living environments and households.
The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently the world's largest public health concern. This study evaluated COVID-19 transmission risks in people in group living environments. A total of 4550 individuals with a history of recent contact with patients at different places (dormitory/home/outside the residences) and levels (close/lower-risk) were tested for SARS-CoV-2 viral RNA using a nasopharyngeal swab test between July 2020 and May 2021. The test-positive rate was highest in individuals who had contact in dormitories (27.5%), but the rates were largely different between dormitories with different infrastructural or lifestyle features and infection control measures among residents. With appropriate infection control measures, the secondary transmission risk in dormitories was adequately suppressed. The household transmission rate (12.6%) was as high as that of close contact outside the residences (11.3%) and accounted for > 60% of the current rate of COVID-19 transmission among non-adults. Household transmission rates synchronized to local epidemics with changed local capacity of quarantining infectious patients. In conclusion, a group living environment is a significant risk factor of secondary transmission. Appropriate infection control measures and quarantine of infectious residents will decrease the risk of secondary transmission in group living environments.


Willingness of Directed Living Donors and Their Recipients to Participate in Kidney Paired Donation Programs.
Participation of compatible living donors and recipients in kidney paired donation (KPD) could double the number of KPD transplants. We determined the willingness of previous directed donors and their recipients to participate in KPD and identified the association of various factors, including financial incentives, with willingness to participate. Survey of previous directed living kidney donors and their recipients in a single Canadian center between 2001 and 2009. Among 207 of 222 eligible living donors contacted, 86 (42%) completed the anonymous survey: 93% (78/86) of donors indicated willingness to participate in KPD if this option had been provided at the time of donation. An increased willingness to participate was reported among the majority of respondents if reimbursements for lost wages and travel expenses were provided; however, cash payments between $5 000 and $50 000 had little impact on willingness. Willingness was also increased with an advantage to the recipient (younger donor or better human leukocyte antigen match), whereas delays beyond 3 months and donor travel were associated with reduced willingness to participate. Among 38 recipients approached during routine clinical follow-up visits over a 3-month period, 100% completed the survey, and 36 of 38 (92%) reported they would have been willing to participate in KPD. Over 90% of directed donors and recipients were willing to participate in KPD. Reimbursement for the costs of participation and improved efficiency of KPD (i.e., eliminating travel and reducing transplant times), but not cash payments, may increase participation of compatible donors and recipients in KPD.