The development and future of reconstructive and microvascular surgery of the hand.
The hand is often thought of as a key discriminator in what makes humans human. The hand is both intricate and fascinating in its design and function, allowing humans to interact with their surroundings, and each other. Due to its use in manipulation of the person's environment, injury to the hand is common. Devastating hand injuries have a profound, physical, psychological, financial and socially crippling effect on patients. Advances in operative techniques and improvements in microscopes and instruments allowed Malt &McKhann to perform the first successful arm replantation in 1962 [1]. This was followed by a myriad of autologous free flaps of varying composition, that were discovered after the mapping of the cutaneous blood circulation by Taylor and Palmer [2] and Mathes & Nahai's classification of muscle flaps [3] providing us with countless options to harvest and transfer healthy, well vascularised tissues into areas of injury. Since the late sixties, with the emerging subspecialty of microvascular reconstruction, surgeons have had the technical ability to salvage many amputated parts, even entire limbs. The measure of functional outcomemust incorporate the evaluation and severity ofthe initial injury and the subsequent reconstructive surgeries [4].


Geographic variability in response to azinphos-methyl in field-collected populations of Cydia pomonella (Lepidoptera: Tortricidae) from Argentina.
Resistance to insecticides has been related to application history, genetic factors of the pest and the dynamic within the treated area. The aim of this study was to assess the geographic variation in azinphos-methyl response and the role of esterase and cytochrome P450 monooxygenase enzymes in codling moth populations collected within different areas of the Río Negro and Neuquén Valley, Argentina. Diapausing field-collected populations showed resistance ratios at the LC(50) that were 0.7-8.7 times higher than that of the susceptible strain. Mean esterase (EST) and cytochrome P450 monooxygenase activities (expressed as α-N min(-1) mg(-1) prot(-1) and pg 7-OHC insect(-1) min(-1) respectively) were significantly correlated with LD(50) values from the field-collected populations. In addition, azinphos-methyl response was associated with the geographic area where the insect population was collected: populations from isolated and more recent productive areas presented significantly lower resistance ratios in comparison with populations from older and more intensive productive areas. The populations assayed presented different resistance levels to azinphos-methyl. The response was highly correlated with the orchard's geographic location. EST and ECOD activities were involved in azinphos-methyl response in the given region.


The diminutive kidney; congenital hypoplasia and atrophic pyelonephritis.
Diminutive kidney, hypoplasia or atrophic pyelonephritis, may be the cause of hypertension, lumbar or abdominal pain, obscure gastrointestinal symptoms or chronic urinary infection accompanied by chills and fever. A hypoplastic kidney is prone to infection and stone formation.Diagnosis includes meticulous x-ray examination and renal function studies employing the more accurate quantitative phenolsulfonphthalein test of each kidney. Nephrectomy is the treatment for unilateral disease causing symptoms; localized atrophic pyelonephritis is amenable to partial resection. Since urinary stasis invites infection, obstructing ureteral strictures should be dilated. Pyelectasis, secondary to ptosis, and ureteropelvic obstruction should be corrected by nephropexy or plastic repair. These conservative measures may prevent renal destruction.SIXTEEN PATIENTS WERE SUBJECTED TO NEPHRECTOMY: Six because of persistent pain and chronic infection and ten because of hypertension. The six with pain and chronic urinary infection were relieved. In six of the ten with hypertension, the disease recurred within six months to seven years.


EPGA: de novo assembly using the distributions of reads and insert size.
In genome assembly, the primary issue is how to determine upstream and downstream sequence regions of sequence seeds for constructing long contigs or scaffolds. When extending one sequence seed, repetitive regions in the genome always cause multiple feasible extension candidates which increase the difficulty of genome assembly. The universally accepted solution is choosing one based on read overlaps and paired-end (mate-pair) reads. However, this solution faces difficulties with regard to some complex repetitive regions. In addition, sequencing errors may produce false repetitive regions and uneven sequencing depth leads some sequence regions to have too few or too many reads. All the aforementioned problems prohibit existing assemblers from getting satisfactory assembly results. In this article, we develop an algorithm, called extract paths for genome assembly (EPGA), which extracts paths from De Bruijn graph for genome assembly. EPGA uses a new score function to evaluate extension candidates based on the distributions of reads and insert size. The distribution of reads can solve problems caused by sequencing errors and short repetitive regions. Through assessing the variation of the distribution of insert size, EPGA can solve problems introduced by some complex repetitive regions. For solving uneven sequencing depth, EPGA uses relative mapping to evaluate extension candidates. On real datasets, we compare the performance of EPGA and other popular assemblers. The experimental results demonstrate that EPGA can effectively obtain longer and more accurate contigs and scaffolds.


Use of indirect addition in adults' mental subtraction in the number domain up to 1,000.
This study examined adults' use of indirect addition and direct subtraction strategies on multi-digit subtractions in the number domain up to 1,000. Seventy students who differed in their level of arithmetic ability solved multi-digit subtractions in one choice and two no-choice conditions. Against the background of recent findings in elementary subtraction, we manipulated the size of the subtrahend compared to the difference and only selected items with large distances between these two integers. Results revealed that adults frequently and efficiently apply indirect addition on multi-digit subtractions, yet adults with higher arithmetic ability performed more efficiently than those with lower arithmetic ability. In both groups, indirect addition was more efficient than direct subtraction both on subtractions with a subtrahend much larger than the difference (e.g., 713 - 695) and on subtractions with a subtrahend much smaller than the difference (e.g., 613 - 67). Unexpectedly, only adults with lower arithmetic ability fitted their strategy choices to their individual strategy performance skills. Results are interpreted in terms of mathematical and cognitive perspectives on strategy efficiency and adaptiveness.


Functional outcomes following catheter-based iliac vein stent placement.
Although previous reports have demonstrated the efficacy of catheter-directed thrombolytic therapy and iliac vein stent placement for the management of iliofemoral deep vein thrombosis (DVT), functional outcomes remain undefined. The purpose of this study was to determine midterm outcomes and functional quality of life among patients treated with iliac vein stenting. Records of all the patients treated with iliac vein stent placement between March 2004 and March 2011 were examined for primary patency, assisted primary patency, and secondary patency. Midterm functional outcomes were measured quantitatively, including ongoing symptoms and return to work status. Over the study interval, 32 patients (33 limbs) underwent iliac vein stent placement. In all, 72% (n = 23) of these patients were female, with an average age of 43 years. In all, 78% (n = 25) of the patients were diagnosed with acute DVT, 89% of which occurred in the left leg. Catheter-directed thrombolysis was utilized in 92% (23 of 25) of the patients with acute DVT. All patients treated with thrombolysis and stent placement presented with pain and edema in the affected limb. One-year primary, assisted primary, and secondary patencies were 75%, 96%, and 96%, respectively. Freedom from reintervention at 1 year was 83%. Treatment was associated with a sustained significant reduction in pain (91% vs 6%, P < .001) and edema (97% vs 12%, P < .001) at a mean follow-up of 29 months (range 5-83 months), at which time 89% of the patients reported to be at their pre-DVT functional status. Aggressive therapy of symptomatic iliac vein stenosis or occlusion with venography, catheter-directed thrombolysis, and iliac vein stent placement provides durable patency and freedom from reintervention. Most patients can anticipate good functional recovery with decreased pain, decreased edema, and high likelihood of returning to work.


Trends in psychotropic use in Saskatchewan from 1983 to 2007.
There has been little research reported on trends in the use of a full spectrum of psychotropics in a general population. We provide an overview of trends in psychotropic use over a 24-year period for Saskatchewan. Data were drawn from the Saskatchewan Ministry of Health administrative data files. It covers antidepressants (ADs), antipsychotics, mood stabilizers, anxiolytics, stimulants, and cholinesterase inhibitors in outpatient settings. We analyzed data from 9 triennial years from 1983 to 2007. Descriptive statistics were used. Among the Saskatchewan population in our study, 8.38% were prescribed at least 1 psychotropic in 1983. The prevalence decreased to 7.44% in 1989, then gradually increased to 12.90% in 2007. We found a continuous increase in the number of psychotropic prescriptions for both males and females. The trend became more marked during the 1990s. Females used more psychotropics. Family physicians were the major prescribers, and their prescriptions dramatically increased over the period. There was an increase in the prescribing of all psychotropics except for anxiolytics. AD prescriptions dramatically increased, especially from 1995 onward. The proportion of patients with 8 to 11 and 12 or more prescriptions per year also gradually increased, whereas the proportion of patients with less than 3 prescriptions per year decreased. AD prescriptions are the major reason for the increasing trend of psychotropic use. Given the major role of family physicians in the use of psychotropics, the need for appropriate training and continuing education is reinforced.


New Sulfated Polyhydroxysteroids from the Antarctic Ophiuroid Astrotomaagassizii
Three new and two known sulfated steroidal polyols have been isolated from the Antarctic ophiuroid Astrotoma agassizii. All of the new steroids possess a terminal isopropenyl group and a C-21 sulfoxy moiety in the side chain but differ in the steroidal nuclei. The structures of these new steroids were established from spectral and chemical correlations with related steroids as (20R)-cholesta-5,24-diene-2beta,3alpha,21-triol 2,21-disulfate (1), (20R)-5alpha-cholest-24-ene-2beta,3alpha,21-triol 3,21-disulfate (3), and (20R)-cholesta-5,24-diene-2alpha,3alpha,4beta,21-tetrol 3,21-disulfate (5). Analysis of the nonsulfated sterol fraction has shown the presence of cholest-5-en-3beta-ol, cholesta-5,24-dien-3beta-ol and (22E) cholesta-5,22-dien-3beta-ol as the major sterols.


Tropomodulin binds two tropomyosins: a novel model for actin filament capping.
Tropomodulin, a tropomyosin-binding protein, caps the slow-growing (pointed) end of the actin filament regulating its dynamics. Tropomodulin, therefore, is important for determining cell morphology, cell movement, and muscle contraction. For the first time we show that one tropomodulin molecule simultaneously binds two tropomyosin molecules in a cooperative manner. On the basis of the tropomodulin solution structure and predicted secondary structure, we introduced a series of point mutations in regions important for tropomyosin binding and actin capping. Capping activity of these mutants was assayed by measuring actin polymerization using pyrene fluorescence. Using direct methods (circular dichroism and native gel electrophoresis) for detecting tropomodulin/tropomyosin binding, we localized the second tropomyosin-binding site to residues 109-144. Despite previous reports that the second binding site is for erythrocyte tropomyosin only, we found that both short nonmuscle and long muscle alpha-tropomyosins bind there as well, though with different affinities. We propose a model for actin capping where one tropomodulin molecule can bind to two tropomyosin molecules at the pointed end.


Invariant manifolds and global bifurcations.
Invariant manifolds are key objects in describing how trajectories partition the phase spaces of a dynamical system. Examples include stable, unstable, and center manifolds of equilibria and periodic orbits, quasiperiodic invariant tori, and slow manifolds of systems with multiple timescales. Changes in these objects and their intersections with variation of system parameters give rise to global bifurcations. Bifurcation manifolds in the parameter spaces of multi-parameter families of dynamical systems also play a prominent role in dynamical systems theory. Much progress has been made in developing theory and computational methods for invariant manifolds during the past 25 years. This article highlights some of these achievements and remaining open problems.


Leucocytosis induced in rabbits by intravenous or central injection of granulocyte colony stimulating factor.
1. We investigated the effect of intravenous, intracerebroventricular and intrapreoptic injections of human recombinant granulocyte colony stimulating factor (GCSF) on body temperature and acute phase responses in the rabbit, including changes in the plasma concentration of iron, zinc, copper and fibrinogen and in circulating leucocyte count. 2. Neither intravenous nor intracerebroventricular injection of GCSF had any effect on the body temperature. 3. Both the intravenous and the intracerebroventricular injections of GCSF induced a dose-dependent increase in the circulating leucocyte count but neither affected the plasma concentration of iron, zinc, copper and fibrinogen. Furthermore, intrapreoptic injection of GCSF produced leucocytosis but had no effect on the red blood cell count. 4. The present results suggest that GCSF induces leucocytosis through its action on both the peripheral target organs and the central nervous system.


Label propagation with α-degree neighborhood impact for network community detection.
Community detection is an important task for mining the structure and function of complex networks. In this paper, a novel label propagation approach with α-degree neighborhood impact is proposed for efficiently and effectively detecting communities in networks. Firstly, we calculate the neighborhood impact of each node in a network within the scope of its α-degree neighborhood network by using an iterative approach. To mitigate the problems of visiting order correlation and convergence difficulty when updating the node labels asynchronously, our method updates the labels in an ascending order on the α-degree neighborhood impact of all the nodes. The α-degree neighborhood impact is also taken as the updating weight value, where the parameter impact scope α can be set to a positive integer. Experimental results from several real-world and synthetic networks show that our method can reveal the community structure in networks rapidly and accurately. The performance of our method is better than other label propagation based methods.


PARSIMONY, MOLECULAR EVOLUTION, AND BIOGEOGRAPHY: THE CASE OF THE NORTH AMERICAN GIANT SALAMANDER.
To draw biogeographic conclusions about the Central Highlands region of the United States, we reconstructed the phylogeny of hellbender (Cryptobranchus alleganiensis) populations from restriction-site variation in mtDNA. We were unable to root the phylogeny using an outgroup and therefore could not weight restriction-site gains more heavily than site losses. As a result, maximum parsimony results in low phylogenetic resolution because of high levels of homoplasy in the data set. Use of a recently published algorithm based on an explicit model of molecular evolution yielded much greater resolution of the mtDNA relationships. This phylogeny indicates the two subspecies of hellbenders are paraphyletic with respect to one another. Hellbenders found in the southern Ozarks (C. a. bishopi) are either most closely related to populations of C. a. alleganiensis inhabiting the Tennessee River drainage or are so divergent that phylogenetic affinities are undetectable. Extremely low levels of divergence among mtDNA haplotypes found in populations from Pennsylvania, Indiana, Illinois, and the northern Missouri Ozarks suggest a recent, probably post-Pleistocene, invasion of this region from a refugium in one of these areas. Biogeographic hypotheses of the causes and timing of hellbender distributions differ significantly from those postulated from analyses of fish species relationships. Possible reasons for the discrepancy are discussed.


Rescue of dendritic cells from glycolysis inhibition improves cancer immunotherapy in mice.
Inhibition of glycolysis in immune cells and cancer cells diminishes their activity, and thus combining immunotherapies with glycolytic inhibitors is challenging. Herein, a strategy is presented where glycolysis is inhibited in cancer cells using PFK15 (inhibitor of PFKFB3, rate-limiting step in glycolysis), while simultaneously glycolysis and function is rescued in DCs by delivery of fructose-1,6-biphosphate (F16BP, one-step downstream of PFKFB3). To demonstrate the feasibility of this strategy, vaccine formulations are generated using calcium-phosphate chemistry, that incorporate F16BP, poly(IC) as adjuvant, and phosphorylated-TRP2 peptide antigen and tested in challenging and established YUMM1.1 tumours in immunocompetent female mice. Furthermore, to test the versatility of this strategy, adoptive DC therapy is developed with formulations that incorporate F16BP, poly(IC) as adjuvant and mRNA derived from B16F10 cells as antigens in established B16F10 tumours in immunocompetent female mice. F16BP vaccine formulations rescue DCs in vitro and in vivo, significantly improve the survival of mice, and generate cytotoxic T cell (Tc) responses by elevating Tc1 and Tc17 cells within the tumour. Overall, these results demonstrate that rescuing glycolysis of DCs using metabolite-based formulations can be utilized to generate immunotherapy even in the presence of glycolytic inhibitor.


[New methods for the evaluation of bone quality. Assessments of bone quality from bone tissues.]
Indeed DXA and quantitative CT both which measure bone mineral amount are well established methods to predict bone volume, but some clinical studies say that different rates of bone turnover can cause discrepancies between bone mineral density and bone volume. Bone strength is accused to not only bone mineral density but bone quality, and developments of the osteoporosis drugs have made "bone quality" more important in explaining bone strength. Bone quality refers to architecture, turnover, damage accumulation and mineralization. Turnover and microdamage at bone tissue are evaluated only by bone histomorphometry, with which it becomes possible to assess bone quality from bone tissue combination with micro-CT and vibrational spectroscopy.


Feature selection using a piecewise linear network.
We present an efficient feature selection algorithm for the general regression problem, which utilizes a piecewise linear orthonormal least squares (OLS) procedure. The algorithm 1) determines an appropriate piecewise linear network (PLN) model for the given data set, 2) applies the OLS procedure to the PLN model, and 3) searches for useful feature subsets using a floating search algorithm. The floating search prevents the "nesting effect." The proposed algorithm is computationally very efficient because only one data pass is required. Several examples are given to demonstrate the effectiveness of the proposed algorithm.


Macrophages Orchestrate Airway Inflammation, Remodeling, and Resolution in Asthma.
Asthma is a heterogenous chronic inflammatory lung disease with endotypes that manifest different immune system profiles, severity, and responses to current therapies. Regardless of endotype, asthma features increased immune cell infiltration, inflammatory cytokine release, and airway remodeling. Lung macrophages are also heterogenous in that there are separate subsets and, depending on the environment, different effector functions. Lung macrophages are important in recruitment of immune cells such as eosinophils, neutrophils, and monocytes that enhance allergic inflammation and initiate T helper cell responses. Persistent lung remodeling including mucus hypersecretion, increased airway smooth muscle mass, and airway fibrosis contributes to progressive lung function decline that is insensitive to current asthma treatments. Macrophages secrete inflammatory mediators that induce airway inflammation and remodeling. Additionally, lung macrophages are instrumental in protecting against pathogens and play a critical role in resolution of inflammation and return to homeostasis. This review summarizes current literature detailing the roles and existing knowledge gaps for macrophages as key inflammatory orchestrators in asthma pathogenesis. We also raise the idea that modulating inflammatory responses in lung macrophages is important for alleviating asthma.


Seeing but not believing: the structure of glycerol dehydrogenase initially assumed to be the structure of a survival protein from Salmonella typhimurium.
The determination of the crystal structure of a mutant protein using phases based on a previously determined crystal structure of the wild-type protein is often a straightforward molecular-replacement protocol. Such a structure determination may be difficult if there are large-scale structural differences between the wild-type and mutant proteins. In this manuscript, an interesting case is presented of the unintentional crystallization of a contaminant protein which shared some structural features with the presumed target protein, leading to difficulties in obtaining a completely satisfactory molecular-replacement structure solution. It was not immediately evident that the initial structure solution was incorrect owing to the poor quality of the X-ray diffraction data and low resolution. The structure was subsequently determined by improving the quality of the data and following a sequence-independent MarathonMR protocol. The structure corresponded to that of glycerol dehydrogenase, which crystallized as a contaminant, instead of the presumed mutant of a survival protein encoded by Salmonella typhimurium. The reasons why a solution that appeared to be reasonable was obtained with an incorrect protein model are discussed. The results presented here show that a degree of caution is warranted when handling large-scale structure-determination projects.


Bone marrow mesenchymal stem cells suppress IL-9 in adjuvant-induced arthritis.
Interleukin-9 (IL-9) has been shown to be upregulated in rheumatoid arthritis (RA). The exact role of IL-9 has not yet been effectively studied. Mesenchymal stem cells (MSCs) have shown a promising immunomodulatory role towards repairing cartilage and restoring joint function. One of the key problems influencing the therapeutic efficacy of stem cell therapy is the poor cell survival following transplantation. This is attributed to oxidative and inflammatory stresses at the injured sites. Hesperidin (Hsd), a flavanone present in citrus fruits, has been studied as potential therapeutic agents that have anti-oxidant and anti-inflammatory activities. The objective of this study is to evaluate the therapeutic paracrine action of bone marrow MSCs on the IL-9 level in adjuvant-induced arthritis (AIA) and the enhancement effect of Hsd on transplanted MSCs. Articular tissue inflammation and cartilage damage were assessed by histological scoring. Antinuclear autoantibodies, tumour necrosis factor-alpha (TNF-α), IL-9, IL-4, interferon gamma (IFN-δ), and transforming growth factor-beta1 (TGF-β1), as well as malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD) levels, were assessed in spleen tissue homogenates after treatment with MSCs either alone or combined with Hsd for 4 weeks in an AIA rat model. Results of this study confirmed that MSCs decreased IL-9 levels in AIA and provide novel insights into the application of Hsd on MSC-based treatments. Highlights Adjuvant-induced arthritis (AIA) is one of the most widely used models that has a great similarity to rheumatoid arthritis (RA). Few studies in recent years have estimated IL-9 in rheumatic diseases and it remains an understudied cytokine. For the first time, bone marrow mesenchymal stem cells (MSCs) therapy has a vital role in splenocytes IL-9 level and further studies are required. Combined therapy of MSCs with antioxidants as hesperidin (Hsd) can alleviate oxidative stress and enhance stem cells immunomodulatory action.


The Optical Janus Effect: Asymmetric Structural Color Reflection Materials.
Structurally colored materials are often used for their resistance to photobleaching and their complex viewing-direction-dependent optical properties. Frequently, absorption has been added to these types of materials in order to improve the color saturation by mitigating the effects of nonspecific scattering that is present in most samples due to imperfect manufacturing procedures. The combination of absorbing elements and structural coloration often yields emergent optical properties. Here, a new hybrid architecture is introduced that leads to an interesting, highly directional optical effect. By localizing absorption in a thin layer within a transparent, structurally colored multilayer material, an optical Janus effect is created, wherein the observed reflected color is different on one side of the sample than on the other. A systematic characterization of the optical properties of these structures as a function of their geometry and composition is performed. The experimental studies are coupled with a theoretical analysis that enables a precise, rational design of various optical Janus structures with highly controlled color, pattern, and fabrication approaches. These asymmetrically colored materials will open applications in art, architecture, semitransparent solar cells, and security features in anticounterfeiting materials.


Quantifying the differences in call detail records.
The increasing availability of mobile phone data has attracted the attention of several researchers interested in studying our collective behaviour. Our interactions with the phone network can take several forms, from SMS messages to phone calls and data usage. Typically, mobile phone data are released to researchers in the form of call detail records, which contain records of different types of interactions, and can be used to analyse various aspects of our behaviour. However, the inherently behavioural nature of these interactions may result in differences between how we make phone calls and receive text messages. Studies which rely on data derived from these interactions, therefore, need to carefully consider these differences. Here, we aim to investigate differences and limitations of different types of mobile phone interactions data by analysing a large mobile phone dataset. We study the relationship between different types of interactions and show how it changes over time. We anticipate our findings to be of interest to all researchers working in the area of computational social science.


The Role of Beliefs and Psychological Factors in Caring of Patients With Cancer: The Lived Experiences of Informal Caregivers.
Cancer affects not only the patient but also family members as informal caregivers. In order for family caregivers to achieve balance and improve their caregiving roles, it is essential to identify the beliefs and psychological aspects affecting them. The present study was carried out qualitatively with a descriptive phenomenological design in 2020. The main participants in this study were selected from one of the major referral centers for cancer patients in West Azerbaijan Province, located in northwestern, Iran. Twenty-two family caregivers were selected through a purposive sampling method. Data analysis showed that the 3 main themes of "emotional and religious preconceptions," "feeling committed to caring for beloveds," and "resilience" played a prominent role in family caregivers. These factors led to caregivers' commitment to and responsibility for care. Holistic care necessitates consideration of all aspects of human life. The results of this study led to an understanding of the complex tendencies and feelings of family caregivers. Based on the results, it was found that care is influenced by beliefs, religious preconceptions, sociocultural, and psychological factors. Identifying these variables helps medical staff share planning, interventions, and counseling with family caregivers and address issues that affect them.


Physical mapping of the mouse genome.
This review is intended to provide an overview of techniques and a source of reagents for physical mapping of the mouse genome. It focuses on those applications, methods, or resources unique to the mouse and on the generation of comparative physical maps. The reference list is not comprehensive; rather, recent reviews on each topic and selected representative examples are given.


Bioavailability of cellobiose by tolerance test and breath hydrogen excretion in humans.
Prebiotic substances have the property of intestinal fermentation. Cellobiose has a beta-1,4 linkage, so it is resistant to hydrolysis by human small intestinal disaccharidase and, hence, reaches the colon undigested. Until this study, it was unclear whether cellobiose has fermentability or bioavailability. The objectives of this study were to clarify whether cellobiose is fermented in the large intestine and to estimate the available energy from cellobiose intake by using tolerance tests and breath hydrogen tests in healthy female subjects. Ten healthy young women (20.5 +/- 2.1 y) who did not develop diarrhea after ingesting 30 g of cellobiose in a previous experiment were recruited. Tolerance tests and breath hydrogen tests for 25 g of cellobiose or glucose were carried out at least 2 wk apart. Blood samples were collected before and at 30-min intervals up to 3 h after ingestion. Breath gas samples were collected simultaneously before and at 30-min intervals up to 6 h after ingestion of cellobiose or glucose. Blood glucose and insulin levels and the concentration of breath hydrogen were analyzed. When 25 g of cellobiose was ingested, there was no increase in blood glucose or insulin secretion, but these markers increased remarkably with glucose ingestion. The excretion of breath hydrogen gas after cellobiose ingestion was significantly greater than that after glucose ingestion. Orally ingested cellobiose was well fermented in human large intestine, and its available energy was estimated to be about 2 kcal/g.


Experiential curriculum improves medical students' ability to answer clinical questions using the internet.
Teaching about evidence-based medicine (EBM) is widespread, yet physicians still use rapid references preferentially over EBM techniques such as literature searching and appraisal of original research. The Internet now provides rapid access to preappraised evidence. We provided clinically integrated teaching of using the Internet to answer clinical questions for third-year medical students and assessed the change in their search skills. The curriculum included two 90-minute computer lab sessions with teaching of search skills related to clinical questions. Immediately before the first and after the second session, students recorded sites searched, time needed for searching, and answers found for three standardized questions. Pretest and posttest questions were matched and reversed with each block. Eighty-six students completed pretests and posttests. For two questions about conventional medical care, posttest answer quality was significantly higher, and posttest search times were significantly shorter, by 1.6 minutes for question 1 (mean pretest search time 6.3 minutes, mean posttest search time 4.7 minutes) and 1.9 minutes for question 2 (mean pretest search time 8 minutes, mean posttest search time 6.1 minutes). For a question about herbal medicine, results were similar, but there were smaller differences that did not reach statistical significance. Students used or found significantly fewer sites on the posttest than on the pretest to find answers for all three question types (absolute difference=0.3 sites for each question). CONCLUSIONS Introducing students to useful Web sites, practicing answering clinical questions, and integrating this process with clinical rotation experiences can reduce the effort that students need to find answers and improve the quality of answers they find.


Comparison of three scores to screen for delirium in the recovery room.
Delirium is often seen in the recovery room and is a predictor for postoperative delirium on the ward. However, monitoring to detect delirium in the recovery room as a basic prerequisite for early intervention is rarely used. The aim of this study was to identify a valid and easy-to-use test for early screening of delirium in the recovery room. One hundred and fifty-four adult patients admitted to the recovery room during regular working hours were included. A screening assessment for delirium was performed in the recovery room by a trained research team at the time when the patient was judged to be 'ready for discharge'. Delirium monitoring was performed with the Confusion Assessment Method (CAM), the Delirium Detection Score (DDS), and the Nursing Delirium Screening Scale (Nu-DESC). The Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV criteria were used as the gold standard. Delirium in the recovery room was seen in 21 patients (14%) with the DSM-IV criteria, in 11 patients (7%) with the CAM, in four patients (3%) with the DDS, and in 37 patients (24%) with the Nu-DESC. Sensitivity and specificity were 0.43 and 0.98 for the CAM, 0.14 and 0.99 for the DDS, and 0.95 and 0.87 for the Nu-DESC, respectively. All scores used were very specific, but the CAM and the DDS were less sensitive compared with the gold standard. Overall, the Nu-DESC was the most sensitive test in the recovery room to detect delirium.


Effects of strain of chickens and vaccination with turkey herpesvirus on Marek's disease and lymphoid leukosis in breeding stocks.
1. A total of 3236 females from eight meat-type strains, half of which were vaccinated for Marek's disease (MD), and 11,193 Leghorn females from ten strains, all vaccinated for MD, were adventitiously exposed to MD and lymphoid leukosis (LL) viruses and observed to 392 and 497 d of age, respectively. 2. In the meat-type birds, vaccination reduced total mortality from 43-4% to 27-1% and mortality due to MD from 16-4% to 5-4% but did not affect mortality and LL (2-9% and 3-4%). 3. In the vaccinated Leghorns total mortality was 11%, including 2-1% from MD and 1-2% from LL. 4. Significant differences between strains of chickens were found in total mortality, as well as in MD and LL mortality. 5. Strain by vaccination interaction was observed in total rearing and adult mortality, as well as in the MD mortality of adult meat-type females. 6. Leghorn strains with higher rate of egg production and meat-type strains with lower growth rate to have better viability.


Resemblance in dietary habits and calcaneal ultrasound attenuation in malay mother-daughter pairs.
The relationship between dietary habits and bone health status was evaluated in 61 pairs of premenopausal mothers and their biological daughters aged 10-19 years. Subjects were volunteers living in Kuala Lumpur. Bone status of the calcaneus was assessed using Quantitative Ultrasound (QUS) which measured the Broadband Ultrasound Attenuation (BUA; in units of dB/MHz) of the bone. Daily nutrient intake of all subjects was evaluated using a 3-day dietary record. Reproductive history, food intake habits, and physical activity level were assessed using questionnaires. Bone health status of mothers (mean BUA of 98.0 ± 15.8 dB/MHz) was significantly higher (p<0.001) compared to their daughters (mean BUA of 86.4 ± 17.0 dB/MHz). BUA (r=0.30, p<0.05), weight (r=0.30, p<0.05) and BMI (r=0.32, p<0.05) were significantly correlated within mother-daughter pairs. Lifestyle characteristics such as calcium intake and physical activity were not correlated. However, other dietary habits (energy intake, milk intake and frequency of skipping meals) in daughters were significantly correlated with their mothers. This study suggests that mothers play an important role in influencing the dietary habits of their daughters, which in turn may affect their bone health status.


Automated Management of Exercise Intervention at the Point of Care: Application of a Web-Based Leg Training System.
Recent advances in information and communication technology have prompted development of Web-based health tools to promote physical activity, the key component of cardiac rehabilitation and chronic disease management. Mobile apps can facilitate behavioral changes and help in exercise monitoring, although actual training usually takes place away from the point of care in specialized gyms or outdoors. Daily participation in conventional physical activities is expensive, time consuming, and mostly relies on self-management abilities of patients who are typically aged, overweight, and unfit. Facilitation of sustained exercise training at the point of care might improve patient engagement in cardiac rehabilitation. In this study we aimed to test the feasibility of execution and automatic monitoring of several exercise regimens on-site using a Web-enabled leg training system. The MedExercise leg rehabilitation machine was equipped with wireless temperature sensors in order to monitor its usage by the rise of temperature in the resistance unit (Δt°). Personal electronic devices such as laptop computers were fitted with wireless gateways and relevant software was installed to monitor the usage of training machines. Cloud-based software allowed monitoring of participant training over the Internet. Seven healthy participants applied the system at various locations with training protocols typically used in cardiac rehabilitation. The heart rates were measured by fingertip pulse oximeters. Exercising in home chairs, in bed, and under an office desk was made feasible and resulted in an intensity-dependent increase of participants' heart rates and Δt° in training machine temperatures. Participants self-controlled their activities on smart devices, while a supervisor monitored them over the Internet. Individual Δt° reached during 30 minutes of moderate-intensity continuous training averaged 7.8°C (SD 1.6). These Δt° were used as personalized daily doses of exercise with automatic email alerts sent upon achieving them. During 1-week training at home, automatic notifications were received on 4.4 days (SD 1.8). Although the high intensity interval training regimen was feasible on-site, it was difficult for self- and remote management. Opportunistic leg exercise under the desk, while working with a computer, and training in bed while viewing television were less intensive than dosed exercise bouts, but allowed prolonged leg mobilization of 73.7 minutes/day (SD 29.7). This study demonstrated the feasibility of self-control exercise training on-site, which was accompanied by online monitoring, electronic recording, personalization of exercise doses, and automatic reporting of adherence. The results suggest that this technology and its applications are useful for the delivery of Web-based exercise rehabilitation and cardiac training programs at the point of care.


Anticardiolipin antibodies as a risk factor of atherosclerosis in intermittent claudication.
Anticardiolipin antibodies have been associated as a risk factor of atherosclerosis. The aim of this study was to evaluate the association between anticardiolipin antibodies and intermittent claudication. Forty consecutive patients (33 men, 7 women; age range: 45-84 years, mean 65.5) who were seen in the angiology and vascular surgery department with intermittent claudication were evaluated. Exclusion criteria included prior revascularization, angioplasty, or a history of thrombosis of a lower limb. Forty individuals (23 men, 17 women; age range: 58-82 years, mean 67.1) who attended a support group for senior citizens and who were apparently healthy formed the control group. Anticardiolipin antibodies were evaluated by means of enzyme-linked immunosorbent assay (ELISA) for quantitative measurement of immunoglobulin G (IgG) and IgM antibodies against cardiolipins in serum. IgG levels were considered normal when < 7, borderline from 7 to 10, and elevated at > 10 GPL units/mL; IgM levels were normal when < 4, borderline from 4 to 7, and elevated at > 7 MPL, as recommended by the test manufacturers. Statistical analysis used the relative risk test with a confidence interval of 95%. Twenty-three patients from the study group and 6 individuals from the control group were found to have elevated levels of anticardiolipin antibodies giving a relative risk of 3.833 (ranging from 1.749 to 8.4; p value < 0.0001). In conclusion, patients who have elevated levels of anticardiolipin antibodies present a 3.8 times greater risk of developing intermittent claudication.


[Multi-scale ecological security evaluation of typical fragile areas in Loess Plateau].
Regional ecological security has been paid more and more attention, and it's of special significance to study the ecological security and its driving factors in ecological fragile areas. In this paper, the ecological security and its driving factors in typical fragile regions in Loess Plateau were analyzed at district and county scales. Yulin District and Hengshan County were taken as the cases, and ecological security index system was constructed to assess the security levels of the two regions. By using AHP method, the spatial differentiation of ecological security at different scales was studied, and the results showed that there existed differences among the twelve counties in Yulin District, with the security level being generally higher in southwest and lower in northeast. Similar tendency was observed in Hengshan County, with the security level being lower in north and northeast, and varying among different scales in southwest. Climate and topography were the weak driving forces, while human disturbances had great influence on ecological security.


National and regional assessment of antimicrobial resistance among community-acquired respiratory tract pathogens identified in a 2005-2006 U.S. Faropenem surveillance study.
Surveillance studies conducted in the United States over the last decade have revealed increasing resistance among community-acquired respiratory pathogens, especially Streptococcus pneumoniae, that may limit future options for empirical therapy. The objective of this study was to assess the scope and magnitude of the problem at the national and regional levels during the 2005-2006 respiratory season (the season when community-acquired respiratory pathogens are prevalent) in the United States. Also, since faropenem is an oral penem being developed for the treatment of community-acquired respiratory tract infections, another study objective was to provide baseline data to benchmark changes in the susceptibility of U.S. respiratory pathogens to the drug in the future. The in vitro activities of faropenem and other agents were determined against 1,543 S. pneumoniae isolates, 978 Haemophilus influenzae isolates, and 489 Moraxella catarrhalis isolates collected from 104 U.S. laboratories across six geographic regions during the 2005-2006 respiratory season. Among S. pneumoniae isolates, the rates of resistance to penicillin, amoxicillin-clavulanate, and cefdinir were 16, 6.4, and 19.2%, respectively. The least effective agents were trimethoprim-sulfamethoxazole (SXT) and azithromycin, with resistance rates of 23.5 and 34%, respectively. Penicillin resistance rates for S. pneumoniae varied by region (from 8.7 to 22.5%), as did multidrug resistance rates for S. pneumoniae (from 8.8 to 24.9%). Resistance to beta-lactams, azithromycin, and SXT was higher among S. pneumoniae isolates from children than those from adults. beta-Lactamase production rates among H. influenzae and M. catarrhalis isolates were 27.4 and 91.6%, respectively. Faropenem MICs at which 90% of isolates are inhibited were 0.5 mug/ml for S. pneumoniae, 1 mug/ml for H. influenzae, and 0.5 mug/ml for M. catarrhalis, suggesting that faropenem shows promise as a treatment option for respiratory infections caused by contemporary resistant phenotypes.


Changing infant mortality: the need to spend more while getting less.
A steady decline of infant and maternal mortality has been recorded for as long as these statistics have been collected. Much of the improvement has been due to reductions in infectious diseases and to social, economic, and public health improvements over the years. The major portion of mortality reductions took place before there were any important effects of medical care. However, there is increasing evidence suggesting that important benefits, can still be gained from medical technology. But, with infant mortality at low levels (between 7 and 12/1,000 live births in high-income countries) the wide use of high technology to effect further reductions guarantees escalating medical care expenditures. With pressures mounting to control costs, what will society be willing to give up in order to make this care available? From where will funds come to utilize costly existing and new medical technology so that all expectant mothers and newborns needing it may have essentially unlimited access in order to reap potential benefits?


Data on six short-tandem repeat polymorphisms in an autochthonous Basque population.
Population data studies for six short-tandem repeat loci (HUMCSF1P0, HUMTPOX, HUMTH01, HUMHPRTB, HUMFES/FPS, and HUMvWF) were carried out on a sample of 326 autochthonous Basques. Comparing with other European samples, we found the highest frequencies known so far for allele 11 of the HUMCSF1P0 locus (0.380), allele 10 of the HUMFES/FPS locus (0.384), and allele 17 of the HUMvWF locus (0.329). On the other hand, we found the lowest frequencies recorded in Europe for allele 12 of the HUMCSF1P0 locus (0.291), allele 7 of the HUMTH01 locus (0.128), and allele 11 of the HUMFES/FPS system (0.317). These results support the hypothesis that the Basque population is a remnant of early European settlers.


Children with atopic dermatitis and frequent emollient use have increased urinary levels of low-molecular-weight phthalate metabolites and parabens.
Parabens may be added to cosmetic and personal care products for preservation purposes. Low-molecular weight (LMW) phthalate diesters function as plasticizers, fixatives or solvents in such products, but may also be found in small quantities as contaminants from plastic containers. To evaluate the association between emollient use, atopic dermatitis and FLG mutations, respectively, with urinary concentrations of phthalate metabolites and parabens in Danish children. Eight hundred and forty-five Danish children 4-9 years of age were studied. Urinary concentrations of phthalate metabolites and parabens were determined, and children were genotyped for common FLG loss-of-function mutations. Information about atopic dermatitis and use of emollients was obtained from questionnaires completed by parents. The prevalence of atopic dermatitis was 16.1%. Phthalate metabolite and paraben levels were generally higher in children with frequent use of emollients compared to uncommon users, reaching statistical significance for some LMW phthalates and parabens. While there was no association with common FLG mutations, children with atopic dermatitis had significantly higher urinary levels of one LMW phthalate and two parabens, respectively, when compared to children without atopic dermatitis. Emollient use and atopic dermatitis were associated with modestly increased internal LMW phthalate and paraben exposure in 4-9 year old children. It is unknown whether the difference is explained by increased use of the specific emollients that are used to treat pruritic and inflamed skin, and/or whether the impaired skin barrier allows chemicals to penetrate more easily. Moreover, the putative toxicological burden is unknown.


[RESEARCH PROGRESS OF ADIPOSE-DERIVED STEM CELLS COMPOUND WITH THREE DIMENSIONAL PRINTING SCAFFOLD FOR ENGINEERED TISSUE].
To review the research progress of adipose-derived stem cells (ADSCs) compound with three dimensional (3D) printing scaffold in tissue engineering of fat, bone, cartilage, blood vessel, hepatocyte, and so on. The recently published literature about ADSCs compound with 3D printing scaffold in tissue engineering at home and abroad was reviewed, analyzed, and summarized. A large number of basic researches showed that ADSCs could differentiate into a variety of tissues on 3D printing scaffold and involve in tissue repair and regeneration. But there is still a long way between the basic theory and the clinical practice at the early stages of development. It can effectively improve and restore the structure and function of the damaged tissue and organ to use ADSCs and 3D printing scaffold.


Sustained Pituitary T3 Production Explains the T4-mediated TSH Feedback Mechanism.
The regulation of thyroid activity and thyroid hormone (TH) secretion is based on feedback mechanisms that involve the anterior pituitary TSH and medial basal hypothalamus TSH-releasing hormone. Plasma T3 levels can be "sensed" directly by the anterior pituitary and medial basal hypothalamus; plasma T4 levels require local conversion of T4 to T3, which is mediated by the type 2 deiodinase (D2). To study D2-mediated T4 to T3 conversion and T3 production in the anterior pituitary gland, we used mouse pituitary explants incubated with 125I-T4 for 48 hours to measure T3 production at different concentrations of free T4. The results were compared with cultures of D1- or D2-expressing cells, as well as freshly isolated mouse tissue. These studies revealed a unique regulation of the D2 pathway in the anterior pituitary gland, distinct from that observed in nonpituitary tissues. In the anterior pituitary, increasing T4 levels reduced D2 activity slightly but caused a direct increase in T3 production. However, the same changes in T4 levels decreased T3 production in human HSkM cells and murine C2C12 cells (both skeletal muscle) and mouse bone marrow tissue, which reached zero at 50 pM free T4. In contrast, the increase in T4 levels caused the pig kidney LLC-PK1 cells and kidney fragments to proportionally increase T3 production. These findings have important implications for both physiology and clinical practice because they clarify the mechanism by which fluctuations in plasma T4 levels are transduced in the anterior pituitary gland to mediate the TSH feedback mechanism.


Trends in mode of delivery for gastroschisis infants.
Cesarean delivery for infants with gastroschisis has not been clearly demonstrated to produce superior outcomes compared with vaginal delivery; however, it not clear whether this has been translated into common clinical practice. Therefore, we analyzed the shifts in type of delivery during the last three decades at our institution. The medical records of all infants with gastroschisis treated at our hospital during the last 33 years were reviewed. Two groups, based on mode of delivery, were compared with regard to demographics, treatment, and outcome. A statistical analysis of changes in type of delivery was performed, and compared with the neonatal population as a whole. A total of 222 patients with gastroschisis were analyzed: 103 delivered via cesarean section and 119 delivered via vaginal birth. Logistic regression demonstrated a significant trend toward cesarean delivery over time (p=0.0001). The odds ratio indicated a 16% per year increase in the chance of cesarean delivery. There has been a significant trend toward cesarean delivery in patients with gastroschisis treated at our institution.


Electrophysiological parameters in the evaluation of occipital apoplexy.
Visual evoked responses (VER) in four cases of occipital apoplexy supplemented perimetric diagnosis with new electrophysiologic parameters. These included diagnosis of (1) optic radiation involvement by delay in the initial VER component; (2) stirate cortical involvement by obliteration of the initial and late VER components; (3) suprastriate involvement by selective loss of the late VER components, and (4) recovery at one or more of the above levels in the visual process by follow-up examination.


Treatment of anthracycline extravasation with Savene (dexrazoxane): results from two prospective clinical multicentre studies.
The purpose of this study was to assess the efficacy and tolerability of i.v. dexrazoxane [Savene (EU), Totect (US)] as acute antidote in biopsy-verified anthracycline extravasation. Two prospective, open-label, single-arm, multicentre studies in patients with anthracycline extravasation were carried out. Patients with fluorescence-positive tissue biopsies were treated with a 3-day schedule of i.v. dexrazoxane (1000, 1000, and 500 mg/m(2)) starting no later than 6 h after the incident. Patients were assessed for efficacy (the possible need for surgical resection) and toxicity during the treatment period and regularly for the next 3 months. In 53 of 54 (98.2%) patients assessable for efficacy, the treatment prevented surgery-requiring necrosis. One patient (1.8%) required surgical debridement. Thirty-eight patients (71%) were able to continue their scheduled chemotherapy without postponement. Twenty-two patients (41%) experienced hospitalisation due to the extravasation. Mild pain (10 patients; 19%) and mild sensory disturbances (nine patients; 17%) were the most frequent sequelae. Haematologic toxicity was common as expected from the fact that the extravasation occurred during a chemotherapy course. Other toxic effects were transient elevation of alanine aminotransferases, nausea, and local pain at the dexrazoxane injection site. Dexrazoxane proved to be an effective and well-tolerated acute treatment with only one out of 54 assessable patients requiring surgical resection (1.8%).


Etiologies of nontraumatic feline uveitis in the UK: A retrospective observational study of 72 cats.
Uveitis is a common ophthalmic diagnosis in cats, that can lead to discomfort and loss of vision. Identification of nonidiopathic cases facilitates treatment and could reduce morbidity associated with this condition. To evaluate etiologies of nontraumatic uveitis in the UK, to compare diagnostic features between idiopathic cases and those with an established underlying etiology, and to investigate the association of clinical signs and abnormal diagnostic findings with a confirmed etiology. Records of cats diagnosed with uveitis at a UK referral center between August 2009 and April 2018 were retrospectively reviewed, excluding traumatic (and reflex) cases. Cases were categorized based on whether an underlying etiology had been established in cases with confirmed etiology, idiopathic, and inconclusive cases. All cases had a minimum of 12-month follow-up unless an underlying etiology had been established. Population characteristics, clinical signs, diagnostic investigation features, and results were reported. 72 cases of uveitis were included, of which male cats and domestic breeds were overrepresented. An underlying etiology was determined in 23.6% of cases: 9.7% had infectious diseases, 5.6% had systemic neoplasia, 4.2% had primary ocular neoplasia, and 4.2% had metabolic disease. Idiopathic uveitis comprised 37.5% of cases, and the remaining 38.9% were inconclusive, of which 35.7% died or were euthanased within the follow-up period. Among the study population, no significant age difference was found between cats with idiopathic disease or confirmed etiology. The unilateral disease was reported in 56.9% of cases and was not different across the idiopathic cases and confirmed etiology groups. The most common ophthalmic clinical sign was an aqueous flare, followed by keratic precipitates and hypotony. Iris color change (p = 0.015) and the presence of an intraocular mass (p = 0.025) were associated with an underlying etiology. Idiopathic uveitis was found to be the most common diagnosis in this study population. However, a similar proportion of cases had possible underlying etiologies as a high proportion manifested systemic disease within the follow-up time. An underlying etiology could be established only in a quarter of cases. Further studies are required to standardize the investigations required when assessing cats with uveitis to minimize patient morbidity.


Monocyclic monoterpenes as penetration enhancers of ligustrazine hydrochloride for dermal delivery.
The purpose of this study was to explore the enhancing effects and the mechanism of monocyclic monoterpene penetration enhancers (menthol and menthone) on the transdermal absorption of ligustrazine hydrochloride (LH). Franz-type diffusion cells were used to determine percutaneous parameters of LH in vitro and surface changes of porcine skin were studied by a scanning electron microscope (SEM). The effects of promoters on the biophysical natures of stratum corneum (SC) were researched by Fourier transform-infrared (FT-IR). Penetration parameters of menthol (p < 0.01) and menthone groups (p < 0.05) were greater than those of the control; morphological changes of skin monitored by SEM demonstrated that the menthone group had the most disruption and desquamation of SC flakes, which resulted from extracted lipids. FT-IR measurements showed menthone had the greatest changes in peak shift and peak area, which resulted from C-H stretching vibrations of SC lipids. The results suggest that the penetration mechanism might include disturbing and extracting SC lipids and the hydrogen bond connection.


The cell surface expressed nucleolin is a glycoprotein that triggers calcium entry into mammalian cells.
Nucleolin is an ubiquitous nucleolar phosphoprotein involved in fundamental aspects of transcription regulation, cell proliferation and growth. It has also been described as a shuttling molecule between nucleus, cytosol and the cell surface. Several studies have demonstrated that surface nucleolin serves as a receptor for various extracellular ligands implicated in cell proliferation, differentiation, adhesion, mitogenesis and angiogenesis. Previously, we reported that nucleolin in the extranuclear cell compartment is a glycoprotein containing N- and O-glycans. In the present study, we show that glycosylation is an essential requirement for surface nucleolin expression, since it is prevented when cells are cultured in the presence of tunicamycin, an inhibitor of N-glycosylation. Accordingly, surface but not nuclear nucleolin is radioactively labeled upon metabolic labeling of cells with [(3)H]glucosamine. Besides its well-demonstrated role in the internalization of specific ligands, here we show that ligand binding to surface nucleolin could also induce Ca(2+) entry into cells. Indeed, by flow cytometry, microscopy and patch-clamp experiments, we show that the HB-19 pseudopeptide, which binds specifically surface nucleolin, triggers rapid and intense membrane Ca(2+) fluxes in various types of cells. The use of several drugs then indicated that Store-Operated Ca(2+) Entry (SOCE)-like channels are involved in the generation of these fluxes. Taken together, our findings suggest that binding of an extracellular ligand to surface nucleolin could be involved in the activation of signaling pathways by promoting Ca(2+) entry into cells.


Combined Calorimetry, Thermo-Mechanical Analysis and Tensile Test on Welded EN AW-6082 Joints.
Wide softening zones are typical for welded joints of age hardened aluminium alloys. In this study, the microstructure evolution and distribution of mechanical properties resulting from welding processes of the aluminium alloy EN AW-6082 (AlSi1MgMn) was analysed by both in-situ and ex-situ investigations. The in-situ thermal analyses (TMA) included differential scanning calorimetry (DSC), which was used to characterise the dissolution and precipitation behaviour in the heat affected zone (HAZ) of welded joints. Thermo-mechanical analysis by means of compression tests was used to determine the mechanical properties of various states of the microstructure after the welding heat input. The necessary temperature⁻time courses in the HAZ for these methods were measured using thermocouples during welding. Additionally, ex-situ tensile tests were done both on specimens from the fusion zone and on welded joints, and their in-depth analysis with digital image correlation (DIC) accompanied by finite element simulations serve for the description of flow curves in different areas of the weld. The combination of these methods and the discussion of their results make an essential contribution to understand the influence of welding heat on the material properties, particularly on the softening behaviour. Furthermore, the distributed strength characteristic of the welded connections is required for an applicable estimation of the load-bearing capacity of welded aluminium structures by numerical methods.


Ascorbic acid, carotenoids, and visual quality of baby spinach as affected by shade netting and postharvest storage.
Baby spinach ( Spinacia oleracea L.) was grown under three types of shade netting (high transmittance, spectrum-altering, and low transmittance) to study the effect on the concentrations of vitamin C (ascorbic acid and dehydroascorbic acid), carotenoids, and chlorophyll and on the visual quality of the leaves. The spinach was sown in April and August and harvested at two growth stages. After harvest, leaves were stored in polypropylene bags at 2 and 10 degrees C. Shading significantly decreased the ascorbic acid concentration of April-sown spinach by 12-33%, but in the August-sown spinach, the response was inconsistent. Concentrations of total carotenoids and total chlorophylls were significantly higher under the nettings in many cases, especially under the spectrum-altering and low-transmittance nettings. Postharvest visual quality and postharvest persistence of the compounds analyzed were not greatly affected by shading. We conclude that these shade nettings are acceptable to use in baby spinach production when it comes to the studied aspects of internal and external quality of the produce.


Structure of YAG crystals doped/substituted with erbium and ytterbium.
Two series of yttrium aluminum garnets doped with erbium and ytterbium ions have been studied by single-crystal X-ray diffraction. The single crystals were obtained by the Czochralski method. The concentration of doping ions was established by the plasma emission spectroscopy method. For the Er series, it is equal to 23.4, 46.7, 72.5, and 100%, whereas, for Yb-doped YAGs, it equals 26.5, 48.2, 75.9, and 100%. The results are supplemented by the data obtained for pure YAG. The X-ray data for all samples were collected at two temperatures: 295(2) and 102(2) K. Additionally, for YAGs doped with ca. 50% of doping ions, some more detailed temperature measurements were performed. Pure single crystals of ErAG and YbAG were also studied as a function of diffraction angles. Careful single-crystal measurements utilizing a CCD diffractometer revealed the unit cell parameters, which slightly-but significantly-deviate from cubic symmetry. The average unit cell parameters change linearly with the amount of substituting Er and Yb cations, with two different slopes related to the ionic radii. Both of the dodecahedral distances depend linearly on the concentration of the substituting ions, but the longer dodecahedral distance also changes with temperature contrary to the shorter one. There is no correlation between the octahedral interatomic distance [Al(VI)...O] and the unit cell parameter or temperature; however, weak trends appear for the tetrahedral [Al(IV)...O] distance. Such weak trends are just the secondary consequences of the ion substitution taking place at the dodecahedral site. The dependences between the unit cell parameters and the concentration of doping ions allow us to establish concentrations of particular doping ions in mixed (Er, Yb) doped YAGs just on the basis of the measured unit cell parameters and knowledge of the amount of Y.


[Construction of adenoviral vectors expressing miR-30a and miR-30e].
To construct adenoviral vectors expressing mature miRNA-30a and miRNA-30e. The target mmu-miR-30a and mmu-miR-30e genes amplified from mouse genome were digested and linked to the shuttle plasmid pSES-HUS, which was then transformed into competent AdEaseier cells for recombination. The confirmed recombinant plasmids were transfected into Hek-293 cells for production of the adenoviruses pAd-mmu-miR-30a and pAd-mmu-miR-30e. The obtained adenoviruses were used to infect Mefs cells, and the cellular expressions of mmu-miR-30a and mmu-miR-30e were detected using fluorescence quantitative PCR. mmu-miR-30a (357 bp) and mmu-miR-30e (324 bp) containing the restriction sites were amplified and linked to the shuttle plasmid pSES-HUS, which was successfully recombined with AdEasy1. After packaging in Hek-293 cells, the adenoviral vectors were obtained, which caused an increase of mmu-miR-30a expression by 26.46∓7.46 folds and mmu-miR-30e expression by 2.76∓0.25 folds in transfected Mefs cells. We have successfully constructed the adenoviral vectors expressing the mature miRNAs.


Novel approach for the assembly of highly efficient SERS substrates.
In this paper we present the properties of surface-enhanced Raman scattering (SERS) active substrates elaborated by a low-cost approach. Our methodology relying on capillary assembly and soft lithography allows us to generate periodic two-dimensional (2D) matrixes of 100 nm gold nanoparticle patterns in a very precise, cost-efficient, and large-scale manner. For this study, we assembled nanoparticle aggregates of different sizes (one to six particles) in order to determine the influence of the aggregation on the local electric field enhancement. We further demonstrate that this substrate is greatly efficient not only for SERS but also in metal-enhanced fluorescence (MEF) for local enhancement of conventional fluorescence.


Measurement of regional elastic properties of the human aorta. A new application of transesophageal echocardiography with automated border detection and calibrated subclavian pulse tracings.
Evaluation of regional aortic elastic properties in humans has been hampered by the need for invasive techniques to access instantaneous aortic pressure, wall thickness, and cross-sectional area or diameter. In this study, a new noninvasive method is presented for quantification of regional aortic elastic properties. Twenty-five patients were studied during transesophageal echocardiographic procedures. Measurements of instantaneous aortic cross-sectional area were obtained with an automated border detection algorithm applied to short-axis transesophageal two-dimensional echocardiographic images of the proximal descending thoracic aorta. Instantaneous aortic wall thickness was derived from combined two-dimensional targeted M-mode end-diastolic wall thickness and instantaneous aortic area measurements. Instantaneous aortic pressures were estimated from calibrated subclavian pulse tracings recorded simultaneously. Data were digitized to generate aortic area-pressure loops. Regional aortic mechanical properties were quantified in terms of compliance per unit length (C is the slope of the area-pressure regression), aortic midwall radius (Rm), and incremental elastic modulus of the aortic wall (Einc). To assess the independent effect of age, Rm and Einc values were compared at a common level of aortic midwall stress (0.666 x 10(6) dynes/cm2). Mean values (+/- SD) for C, Rm, and Einc were 0.01 +/- 0.004 cm2/mm Hg, 1.14 +/- 0.17 cm, and 7.059 +/- 4.091 x 10(6) dynes/cm2, respectively. An inverse linear correlation was found between aortic compliance per unit length and age (r = -.68, P < .0007). Incremental elastic modulus was related to age (r = +.80, P < .00003) in a nonlinear fashion such that it increased sharply after the age of 60 years. Finally, midwall radius was less tightly correlated with age (r = +.45, P < .05). Values for C, Rm, and Einc as well as the age dependency of these properties are similar to those reported previously when invasive techniques were used. This methodology constitutes a new tool to improve the clinical evaluation of regional aortic elastic properties in multiple disease states.


Guarding embryo development of zebrafish by shell engineering: a strategy to shield life from ozone depletion.
The reduced concentration of stratospheric ozone results in an increased flux of biologically damaging mid-ultraviolet radiation (UVB, 280 to 320 nm) reaching earth surfaces. Environmentally relevant levels of UVB negatively impact various natural populations of marine organisms, which is ascribed to suppressed embryonic development by increased radiation. Inspired by strategies in the living systems generated by evolution, we induce an extra UVB-adsorbed coat on the chorion (eggshell surrounding embryo) of zebrafish, during the blastula period. Short and long UV exposure experiments show that the artificial mineral-shell reduces the UV radiation effectively and the enclosed embryos become more robust. In contrast, the uncoated embryos cannot survive under the enhanced UVB condition. We suggest that an engineered shell of functional materials onto biological units can be developed as a strategy to shield lives to counteract negative changes of global environment, or to provide extra protection for the living units in biological research.


Second-Generation Antipsychotic Prescribing Patterns for Pediatric Patients Enrolled in West Virginia Medicaid.
The prescribing of second-generation antipsychotics for young people has increased dramatically. Studies have shown that children enrolled in Medicaid are more likely than those with private insurance to receive antipsychotics, leading many states to require prior authorization (PA) for their use. However, little is known about how PA programs affect prescribing patterns for antipsychotics or other psychotropic medications. This study examined a PA program for second-generation antipsychotic use for children under 18 in West Virginia Medicaid. Prescribing rates for antipsychotics and other psychotropic classes were assessed. Administrative claims from West Virginia Medicaid and the Children's Health Insurance Program for September 2014 to July 2016 were examined (N=273,369 prescriptions) with an interrupted time-series design. Segmented linear regression was used to model both immediate effects and trends in prescribing rates before and after implementation of the PA program in August 2015. After PA program implementation, the prescribing rate for second-generation antipsychotics immediately dropped by 17% from prior levels, adjusted for preexisting trends, and further declined in the following months. Prescribing rates for all second-generation antipsychotics except for aripiprazole decreased significantly. Benzodiazepine prescribing increased in the month after PA program implementation but immediately returned to prepolicy rates, and sustained compensatory prescribing was not observed for any psychotropic drug class. Implementation of a second-generation antipsychotic PA program for children under age 18 resulted in a significant decrease in the prescribing rate for this class of medication, without sustained compensatory prescribing of other psychotropic classes.


Late survival after abdominal aortic aneurysm repair.
This study was undertaken to determine the late survival of patients operated successfully for abdominal aortic aneurysm (AAA) repair, to compare survival data with that of the age- and sex-matched general population, to identify the causes of late death, and to determine the factors influencing late survival. A total of 187 consecutive patients underwent elective surgical AAA repair between January 1987 and December 1991. There were 11 postoperative deaths (early mortality rate 5.9%). The remaining 176 patients formed the basis of this cohort-based retrospective study. Six patients (3.4%) were lost to follow-up. Mean follow-up was 71 months. A total of 70 patients (39.8%) died during the study period. Coronary artery disease (CAD) and cancer were the two main causes. The survival rate at five years (71.6%) was lower than that of the sex- and age-matched general population (90.6%). Neither arterial hypertension nor CAD had any influence on late survival. In contrast, age and chronic renal failure were predictive variables of late survival. The life expectancy of patients who undergo successful AAA repair is not as good as that of the age- and sex-matched general population. Late survival depends on the patients' age at the time of surgery and the existence of preoperative chronic renal failure.


An exploratory analysis of sociodemographic characteristics with ultrafine particle concentrations in Boston, MA.
Little is known of the relationship between exposure to the smallest particles of air pollution and socio-demographic characteristics. This paper explores linkages between ultrafine particle (UFP) concentrations and indicators of both race/ethnicity and socioeconomic status in Boston, Massachusetts, USA. We used estimates of UFP based on a highly-resolved land-use regression model of concentrations. In multivariate linear regression models census block groups with high proportions of Asians were associated with higher levels of UFP in comparison to block groups with majority White or other minority groups. Lower UFP concentrations were associated with higher homeownership (indicating higher SES) and with higher female head of household (indicating lower socioeconomic status). One explanation for the results include the proximity of specific groups to traffic corridors that are the main sources of UFP in Boston. Additional studies, especially at higher geographic resolution, are needed in Boston and other major cities to better characterize UFP concentrations by sociodemographic factors.


Induction of torsades de pointes by dobutamine infusion in a patient with idiopathic long QT syndrome.
We used a provocative test with dobutamine infusion to diagnose long QT syndrome (LQTS) in a girl with a history of syncope. When dobutamine was infused at a rate of 10 microg/kg/min, the QT interval corrected for heart rate (QTc) was prolonged from 460 ms to 620 ms with abnormal TU complexes and torsades de pointes developed. In 5 control subjects the QTc did not change significantly during low-dose dobutamine infusion. Low-dose dobutamine, in addition to isoproterenol, may be useful for evaluation of prolongation of the QT interval and abnormal TU complexes in patients in whom LQTS is suspected.


Health care reform: what it might mean to urban public hospitals.
Health care reform proposals may affect public hospitals in a number of ways. To insure that such proposals benefit the underserved communities within which public hospitals operate, reform initiatives should be evaluated against 10 criteria that emphasize prevention and primary care, community health education, cost control, tort reform, and community values.


Perceptions of satisfaction, usability and desirability of the DEKA Arm before and after a trial of home use.
To: 1) describe perceptions of satisfaction with and usability of the DEKA Arm and preferences for the DEKA Arm or personal prosthesis; 2) compare perceptions of satisfaction and usability by DEKA Arm configuration level; and 3) evaluate satisfaction and usability for study completers and non-completers; and for those who did and did not want to receive a DEKA Arm. The study had 2 phases: in-laboratory (Part A) and home trial (Part B). 32 participants with amputation, (50% transradial, 38% transhumeral and 13% shoulder) completed Part A and 18 completed Part B 16 (89%) of whom were prosthesis users at baseline. Measures of satisfaction, usability and user preferences were administered. Responses were compared for completers of Part A only and completers of Parts A and B. Preferences for the DEKA Arm over personal prosthesis and proportion of participants who wanted to receive a DEKA Arm were evaluated. Relationships between satisfaction, usability and desire to receive a DEKA Arm were examined. At end of Part A, 22 (69%) of the 32 participants who completed in-laboratory training wanted to receive a DEKA Arm and 5 (16%) might want one. At end of Part B, 14 (88%) of 16 prosthesis users who completed the home trial preferred the overall function of the DEKA Arm, 13 (81%) preferred DEKA hand function and 14 (88%) preferred DEKA wrist function to their own prosthesis. In contrast, 14 (88%) preferred the weight and 13 (81%) preferred the look of their own prosthesis. Most aspects of the DEKA Arm were rated "easy" to use. No items were rated as "difficult". Users were satisfied with most aspects of the DEKA Arm, except for the weight, shoulder appearance and harnessing. There were few differences in perceived usability or satisfaction by configuration level. Findings about desire to receive a DEKA Arm pertain only to study completers. Non-completers viewed the DEKA Arm less favorably than completers. Satisfaction was strongly related to participants' expressed desire to receive a DEKA Arm in the future. To maximize likelihood of adoption of the DEKA Arm, findings suggest that both an in-laboratory and a home use trial may be useful prior to finalizing a recommendation for prescription.


"Devil's staircases" in bulk-immiscible ultrathin alloy films.
Ground-state phase diagrams of ultrathin epitaxial alloy films are studied within the framework of a discrete lattice-model Hamiltonian incorporating competing elastic and chemical interactions. For bulk-immiscible alloy systems an infinite number of commensurate, long-period stripe-superstructure ground states are obtained as a function of chemical potential. The average periodicity of these stripe superstructures is found to be a nonmonotonic function of alloy composition, in contrast to the predictions of continuum theories for two-dimensional systems with competing interactions.


Hedgehog Spin-Vortex Crystal Antiferromagnetic Quantum Criticality in CaK(Fe_{1-x}Ni_{x})_{4}As_{4} Revealed by NMR.
Two ordering states, antiferromagnetism and nematicity, have been observed in most iron-based superconductors (SCs). In contrast to those SCs, the newly discovered SC CaK(Fe_{1-x}Ni_{x})_{4}As_{4} exhibits an antiferromagnetic (AFM) state, called hedgehog spin-vortex crystal (SVC) structure, without nematic order, providing the opportunity for the investigation into the relationship between spin fluctuations and SC without any effects of nematic fluctuations. Our ^{75}As nuclear magnetic resonance studies on CaK(Fe_{1-x}Ni_{x})_{4}As_{4} (0≤x≤0.049) revealed that CaKFe_{4}As_{4} is located close to a hidden hedgehog SVC AFM quantum-critical point (QCP). The magnetic QCP without nematicity in CaK(Fe_{1-x}Ni_{x})_{4}As_{4} highlights the close connection of spin fluctuations and superconductivity in iron-based SCs. The advantage of stoichiometric composition also makes CaKFe_{4}As_{4} an ideal platform for further detailed investigation of the relationship between magnetic QCP and superconductivity in iron-based SCs without disorder effects.


Contingency management for smoking cessation: enhancing feasibility through use of immunoassay test strips measuring cotinine.
Contingency management (CM) is a powerful behavioral intervention shown to reduce the use of a variety of substances including tobacco. Use of CM techniques for smoking cessation has been restricted by the use of multiple daily measurements of breath CO as the objective indicator to reinforce abstinence. Cotinine, with its longer half-life, may be a better marker. We evaluated the use of urinary cotinine (determined using once-daily semiquantitative immunoassay test strips and verified using quantitative GC/HPLC techniques) as an abstinence indicator in treatment-seeking adult and adolescent smokers participating in a CM-based intervention program. Both techniques of determining urinary cotinine were highly sensitive and moderately specific at detecting abstinence, and they were highly concordant. However, specificity was somewhat lower during the first few days of a quit attempt and improved over time. The results were similar in adults and adolescent smokers, and suggest that during the first few days of a quit attempt it would be advisable to continue to use daily multiple CO measurements to verify abstinence. However, once abstinence is achieved, once-daily immunoassay test strips could be used for continued monitoring of urinary cotinine levels. Immunoassay testing can identify individuals who relapse to smoking, though this study cannot evaluate whether the strips can identify resumption of abstinence. These results suggest that the use of cotinine as an abstinence indicator, by reducing the number of daily appointments, could significantly enhance the feasibility and utility of CM-based interventions for smoking cessation.


Adenosine and 2'-deoxyadenosine modified with boron cluster pharmacophores as new classes of human blood platelet function modulators.
Novel types of adenosine and 2'-deoxyadenosine derivatives containing boron clusters at positions C2', N6, or C8 were synthesized. The effect of these modified compounds on platelet function was studied. Modification of adenosine at the C2' position with a para-carborane cluster (C(2)B(10)H(11)) results in efficient inhibition of platelet function, including aggregation, protein secretion, and P-selectin expression induced by thrombin or ADP. These preliminary findings and the new chemistry proposed form the basis for the development of a new class of adenosine analogues that modulate human blood platelet activities.


Coherence in the urban family caregiver role with African American stroke survivors.
Expressions of coherence by urban caregivers in African American family systems are the focus of this ethnographic study. The profound changes that can accompany stroke may create considerable stress for families caring for the affected person. Coherence, a sense of mutuality, and differences in functioning among family members were discovered in this study to be important for maintaining stability within the family. Through coherence, family caregivers felt connected and this helped them survive in stressful times related to caring situations. The findings aid in defining coherence as an interpersonal process and place it in a family system context.


Mutagenesis of a bacteriophage lytic enzyme PlyGBS significantly increases its antibacterial activity against group B streptococci.
Group B streptococci (GBS) are the leading cause of neonatal meningitis and sepsis worldwide. Intrapartum antibiotic prophylaxis (IAP) is the current prevention strategy given to pregnant women with confirmed vaginal GBS colonization. Due to antibiotic resistance identified in GBS, we previously developed another strategy using a bacteriophage lytic enzyme, PlyGBS, to reduce vaginal GBS colonization. In this study, various DNA mutagenesis methods were explored to produce PlyGBS mutants with increased lytic activity against GBS. Several hyperactive mutants were identified that contain only the endopeptidase domain found in the N-terminal region of PlyGBS and represent only about one-third of the wild-type PlyGBS in length. Significantly, these mutants not only have 18-28-fold increases in specific activities compared to PlyGBS, but they also have a similar activity spectrum against several streptococcal species. One of the hyperactive mutants, PlyGBS90-1, reduced the GBS colonization from >5 logs of growth per mouse to <50 colony-forming units (cfu) 4 h post treatment ( approximately 4-log reduction) using a single dose in a mouse vaginal model. A reduction in GBS colonization before delivery should significantly reduce neonatal GBS infection providing a safe alternative to IAP.


Central administration of insulin-like growth factor-2 suppresses food intake in chicks.
Insulin-like growth factor (IGF)-2 is a multifunctional hormone with structural and functional similarity to IGF-1 in mammals and chickens. We previously showed that intracerebroventricular administration of IGF-1 suppresses food intake in chicks. Also, central administration of IGF-2 suppresses food intake in rats. In the present study, we evaluated whether IGF-2 is involved in the regulation of food intake in chicks. We also examined the effects of fasting on the mRNA levels of IGF binding proteins (IGFBPs) in the liver and hypothalamus, because IGFBPs bind IGF-1 and -2 in plasma and block their binding to the receptors, and locally expressed IGFBPs also influence IGFs binding to the receptors in mammals. Intracerebroventricular administration of IGF-2 significantly suppressed food intake in chicks. The mRNA levels of IGFBPs in the hypothalamus were not affected by six hours of fasting. On the other hand, six hours of fasting markedly increased the mRNA levels of hepatic IGFBP-1 and -2 (5.47- and 6.95-fold, respectively). The mRNA levels of IGFBP-3 were also significantly increased (1.36-fold) by six hours of fasting, whereas the mRNA levels of IGF-2, IGFBP-4, and -5 were unchanged. These findings suggest that circulating IGF-2 may be involved in satiety signals, but its physiological role may be regulated by IGFBPs production in the liver in chicks.


Dynamics of self-trapped singular beams in an underdense plasma.
Dynamics of an intense short laser pulse with a phase singularity, propagating in an underdense cold plasma, is investigated. Such a pulse can propagate as a vortex soliton in a self-created channel. It is shown that vortices with the topological charge m=1,2 (and a corresponding angular momentum) are unstable against symmetry-breaking perturbations; the breakup of the original vortex leads to the formation of stable spatial solitons that steadily fly away tangentially from the initial ring of vortex distribution.


Intermediate lobe immunoreactivity in a patient with suspected lymphocytic hypophysitis.
Lymphocytic hypophysitis is an organ-specific autoimmune disease characterised by destruction of pituitary hormone-secreting cells due to attack by self-reactive T lymphocytes. The spectrum of pituitary autoantibodies characterised by indirect immunofluorescence (IF) in these patients has not been substantially defined. The purpose of this study was to determine the spectrum of pituitary autoantibodies in 16 lymphocytic hypophysitis patients. Pituitary sections were prepared from guinea pigs and sera from 16 lymphocytic hypophysitis patients (13 biopsy proven and 3 suspected cases) and 13 healthy controls were evaluated for immunoreactivity to the pituitary tissue by immunofluorescence. A single patient was found to have high titre pituitary autoantibodies against guinea pig pituitary tissue. Immunoreactivity was directed against cells of the intermediate lobe. We present the case report of the patient who is a 24 year old woman that presented with headaches, polyuria and polydipsia. A uniformly enlarged pituitary mass was visible on MRI and a diagnosis of suspected lymphocytic hypophysitis was made. Based on our IF study, we postulate this patient has an autoimmune process directed towards the major cell type in the intermediate lobe, the melanotroph. Pre-adsorption with peptides representing adrenocorticotropic hormone, α-melanocyte stimulating hormone or β-endorphin did not affect the IF signal suggesting our patient's pituitary autoantibodies may target some other product of Proopiomelanocortin (POMC) processing, such as corticotrophin-like intermediate peptide or γ-lipoprotein. Alternatively, the autoantibodies may target a peptide completely unrelated to POMC processing.


Outcome of mammography examination in asymptomatic women.
Early detection of breast cancer is important in reducing mortality, morbidity, and high socioeconomic burden associated with it. Mammography is currently the primary imaging modality used as a screening tool to detect early breast cancer in women experiencing no symptoms as they are most curable in the early stage with availability of breast conservative therapies. This study aimed at determining the mammographic breast density patterns and outcome in asymptomatic women who presented for mammographic examination in Abuja. This descriptive cross-sectional study comprises of 113 asymptomatic women who presented for mammographic examination at the Radiology Department of University of Abuja Teaching Hospital, Gwagwalada from March 2015 to December 2018. Two basic views (craniocaudal and mediolateral views) of the breast were obtained using EXR-650 mammographic machine. The mean age of study population was 40.72 ± 10.45 years with age range of 35 and 65 years. Base on mammographic breast density, breast imaging, reporting, and data system 1 and 2 were the most prevalent. There was a positive correlation between mammographic breast density and age of respondents. This relationship was statistically significant (Pearson correlation = 0.56, P = 0.000). The mammographic outcome among asymptomatic women who had mammographic examination was negative in 69 (61.1%) women and positive in 44 (38.9%). The positive outcome noted in mammograms of women examined was: benign mass in 18 (15.9%) women; 9 (8.0%) had benign calcification; 7 (6.2%) showed architectural distortion; 5 (4.4%) was inconclusive; focal asymmetry in 3 (2.6%); and suspicious mass in 2 (1.8%). In this study, screening of women reveals various benign and malignant breast pathologies which necessitate early interventions.


Predicting the number of article citations on the topic of pemphigus vulgaris with the 100 top-cited articles since 2011: A protocol for systematic review and meta-analysis.
Pemphigus vulgaris (PV) is a rare autoimmune blistering disease characterized by intraepithelial and mucocutaneous blister formation and erosion. Numerous articles related to PV have been published. However, which articles have a tremendous influence is still unknown, and factors affecting article citation numbers remain unclear. We aimed to visualize the prominent entities using the top 100 most-cited articles on the topic of PV (T100PV), and investigate whether medical subject headings (i.e., MeSH terms) can be used to predict article citations. By searching the PubMed Central (PMC) database, the T100PV abstracts since 2011 were downloaded. Citation analysis was performed to compare the dominant entities in article topics, authors, and research institutes using social network analysis (SNA) and Kano diagrams. We examined the MeSH prediction power against article citations using correlation coefficients (CCs). The most cited article (125 times) was authored by Ellebrecht from the University of Pennsylvania in the US. The most productive countries were Germany (28%) and the US (25%). Most articles were published in J Invest Dermatol (16%) and Br J Dermatol (10%). Kasperkiewicz (Germany) and the Normandie University (France) were the most cited authors and research institutes, respectively. The most frequently occurred MeSH terms were administration and dosage, immunology, and metabolism. MeSH terms were evident in the prediction power on the number of article citations (F = 19.77; P < .001). A breakthrough was achieved by developing dashboards to display the T100PV. MeSH terms can be used to predict the T100PV citations. These T100PV visualizations can be applied in future studies.


Tunable Coarse Graining for Monte Carlo Simulations of Proteins via Smoothed Energy Tables: Direct and Exchange Simulations.
Many commonly used coarse-grained models for proteins are based on simplified interaction sites and consequently may suffer from significant limitations, such as the inability to properly model protein secondary structure without the addition of restraints. Recent work on a benzene fluid (Lettieri S.; Zuckerman D. M.J. Comput. Chem.2012, 33, 268-275) suggested an alternative strategy of tabulating and smoothing fully atomistic orientation-dependent interactions among rigid molecules or fragments. Here we report our initial efforts to apply this approach to the polar and covalent interactions intrinsic to polypeptides. We divide proteins into nearly rigid fragments, construct distance and orientation-dependent tables of the atomistic interaction energies between those fragments, and apply potential energy smoothing techniques to those tables. The amount of smoothing can be adjusted to give coarse-grained models that range from the underlying atomistic force field all the way to a bead-like coarse-grained model. For a moderate amount of smoothing, the method is able to preserve about 70-90% of the α-helical structure while providing a factor of 3-10 improvement in sampling per unit computation time (depending on how sampling is measured). For a greater amount of smoothing, multiple folding-unfolding transitions of the peptide were observed, along with a factor of 10-100 improvement in sampling per unit computation time, although the time spent in the unfolded state was increased compared with less smoothed simulations. For a β hairpin, secondary structure is also preserved, albeit for a narrower range of the smoothing parameter and, consequently, for a more modest improvement in sampling. We have also applied the new method in a "resolution exchange" setting, in which each replica runs a Monte Carlo simulation with a different degree of smoothing. We obtain exchange rates that compare favorably to our previous efforts at resolution exchange (Lyman E.; Zuckerman D. M.J. Chem. Theory Comput.2006, 2, 656-666).


Cytokine gene expression profiles in kidney medulla and cortex of obese hypertensive dogs.
The molecular mechanisms linking abnormal kidney function and obesity hypertension are poorly understood. This study compared gene expression profiles in the kidney medulla and cortex of obese and lean dogs. Lean dogs (N= 4) were fed a standard kennel ration and obese dogs (N= 4) were fed the standard diet plus 0.5 to 0.9 kg of cooked beef fat per day for 10 weeks. The dogs were instrumented for continuous monitoring of mean arterial pressure (MAP), heart rate, glomerular filtration rate (GFR), and effective renal plasma flow (RPF). The relative mRNA levels of 375 genes in renal cortex and medulla were determined simultaneously using cDNA membrane arrays (R&D Systems). The high fat diet increased body weight by 57% and MAP increased by 24 mm Hg (112 +/- 1 mm Hg vs. 88 +/- 3 mm Hg) in obese compared to lean dogs. In obese dogs, expression of 11 and 13 genes changed significantly (N= 4; P < 0.05) in the renal medulla and the cortex, respectively, relative to the lean dogs. Differences in renal gene expression profiles between lean and obese dogs were closely related to functional pathways, including those associated with sympathetic activation, inflammatory response, matrix formation, angiogenesis, endothelial dysfunction, attenuated actions of leptin, and attenuated cell survival. A high fat diet in dogs is associated with marked changes in renal gene expression profiles that provide potential molecular links to pathways associated with altered renal function and structure in obesity hypertension.


Incoordination between spikes and LFPs in Aβ1-42-mediated memory deficits in rats.
Alzheimer's disease (AD) is a neurodegenerative disease that gradually induces cognitive deficits. Impairments of working memory have been typically observed in AD. It is well known that spikes and local field potentials (LFPs) as well as the coordination between them encode information in normal brain function. However, the abnormal coordination between spikes and LFPs in the cognitive deficits of AD has remained largely unexplored. As amyloid-β peptide (Aβ) is a causative factor for the cognitive impairments of AD, developing a mechanistic understanding of the contribution of Aβ to cognitive impairments may yield important insights into the pathophysiology of AD. In the present study, we simultaneously recorded spikes and LFPs from multiple electrodes implanted in the prefrontal cortex of rats (control and intra-hippocampal Aβ injection group) that performed a Y-maze working memory task. The information changes in spikes and LFPs during the task were assessed by calculation of entropy. Then the coordination between spikes and LFPs was estimated by the correlation of LFP entropy and spike entropy. Compared with the control group, the Aβ group showed significantly weaker coordination between spikes and LFPs. Our results indicate that the incoordination between spikes and LFPs may provide a potential mechanism for the cognitive deficits in working memory of AD.


The multidrug-resistance transporter MdfA from Escherichia coli: crystallization and X-ray diffraction analysis.
The active efflux of antibiotics by multidrug-resistance (MDR) transporters is a major pathway of drug resistance and complicates the clinical treatment of bacterial infections. MdfA is a member of the major facilitator superfamily (MFS) from Escherichia coli and provides resistance to a wide variety of dissimilar toxic compounds, including neutral, cationic and zwitterionic substances. The 12-transmembrane-helix MdfA was expressed as a GFP-octahistidine fusion protein with a TEV protease cleavage site. Following tag removal, MdfA was purified using two chromatographic steps, complexed with a Fab fragment and further purified using size-exclusion chromatography. MdfA and MdfA-Fab complexes were subjected to both vapour-diffusion and lipidic cubic phase (LCP) crystallization techniques. Vapour-diffusion-grown crystals were of type II, with poor diffraction behaviour and weak crystal contacts. LCP lipid screening resulted in type I crystals that diffracted to 3.4 Å resolution and belonged to the hexagonal space group P6122.