Telementoring in Leg Fasciotomies via Mixed-Reality: Clinical Evaluation of the STAR Platform.
Point-of-injury (POI) care requires immediate specialized assistance but delays and expertise lapses can lead to complications. In such scenarios, telementoring can benefit health practitioners by transmitting guidance from remote specialists. However, current telementoring systems are not appropriate for POI care. This article clinically evaluates our System for Telementoring with Augmented Reality (STAR), a novel telementoring system based on an augmented reality head-mounted display. The system is portable, self-contained, and displays virtual surgical guidance onto the operating field. These capabilities can facilitate telementoring in POI scenarios while mitigating limitations of conventional telementoring systems. Twenty participants performed leg fasciotomies on cadaveric specimens under either one of two experimental conditions: telementoring using STAR; or without telementoring but reviewing the procedure beforehand. An expert surgeon evaluated the participants' performance in terms of completion time, number of errors, and procedure-related scores. Additional metrics included a self-reported confidence score and postexperiment questionnaires. STAR effectively delivered surgical guidance to nonspecialist health practitioners: participants using STAR performed fewer errors and obtained higher procedure-related scores. This work validates STAR as a viable surgical telementoring platform, which could be further explored to aid in scenarios where life-saving care must be delivered in a prehospital setting.


Sample size and power calculations for open cohort longitudinal cluster randomized trials.
When calculating sample size or power for stepped wedge or other types of longitudinal cluster randomized trials, it is critical that the planned sampling structure be accurately specified. One common assumption is that participants will provide measurements in each trial period, that is, a closed cohort, and another is that each participant provides only one measurement during the course of the trial. However some studies have an "open cohort" sampling structure, where participants may provide measurements in variable numbers of periods. To date, sample size calculations for longitudinal cluster randomized trials have not accommodated open cohorts. Feldman and McKinlay (1994) provided some guidance, stating that the participant-level autocorrelation could be varied to account for the degree of overlap in different periods of the study, but did not indicate precisely how to do so. We present sample size and power formulas that allow for open cohorts and discuss the impact of the degree of "openness" on sample size and power. We consider designs where the number of participants in each cluster will be maintained throughout the trial, but individual participants may provide differing numbers of measurements. Our results are a unification of closed cohort and repeated cross-sectional sample results of Hooper et al (2016), and indicate precisely how participant autocorrelation of Feldman and McKinlay should be varied to account for an open cohort sampling structure. We discuss different types of open cohort sampling schemes and how open cohort sampling structure impacts on power in the presence of decaying within-cluster correlations and autoregressive participant-level errors.


Analysis of human mRNAs with the reference genome sequence reveals potential errors, polymorphisms, and RNA editing.
The NCBI Reference Sequence (RefSeq) project and the NIH Mammalian Gene Collection (MGC) together define a set of approximately 30,000 nonredundant human mRNA sequences with identified coding regions representing 17,000 distinct loci. These high-quality mRNA sequences allow for the identification of transcribed regions in the human genome sequence, and many researchers accept them as the correct representation of each defined gene sequence. Computational comparison of these mRNA sequences and the recently published essentially finished human genome sequence reveals several thousand undocumented nonsynonymous substitution and frame shift discrepancies between the two resources. Additional analysis is undertaken to verify that the euchromatic human genome is sufficiently complete--containing nearly the whole mRNA collection, thus allowing for a comprehensive analysis to be undertaken. Many of the discrepancies will prove to be genuine polymorphisms in the human population, somatic cell genomic variants, or examples of RNA editing. It is observed that the genome sequence variant has significant additional support from other mRNAs and ESTs, almost four times more often than does the mRNA variant, suggesting that the genome sequence is more accurate. In approximately 15% of these cases, there is substantial support for both variants, suggestive of an undocumented polymorphism. An initial screening against a 24-individual genomic DNA diversity panel verified 60% of a small set of potential single nucleotide polymorphisms from which successful results could be obtained. We also find statistical evidence that a few of these discrepancies are due to RNA editing. Overall, these results suggest that the mRNA collections may contain a substantial number of errors. For current and future mRNA collections, it may be prudent to fully reconcile each genome sequence discrepancy, classifying each as a polymorphism, site of RNA editing or somatic cell variation, or genome sequence error.


An IgE-binding protein with a distinctive repetitive sequence and homology with an IgG receptor.
Proteins that bind IgE play important roles in both the synthesis and function of IgE are therefore intimately involved in IgE-mediated human allergic disorders. This report describes the structure of an IgE-binding protein, as predicted from sequencing a cDNA cloned from rat basophilic leukemia cells. This protein contains two domains: the amino-terminal domain (140 amino acids) consists of a highly conserved repetitive amino acid sequence, Tyr-Pro-Gly-Pro/Gln-Ala/Thr-Pro/Ala-Pro-Gly-Ala, whereas the carboxyl-terminal domain (122 amino acids) shares significant sequence homology with a domain of lymphocyte/macrophage receptor for the Fc portion of IgG. Other proteins with this type of structure but with affinity for other immunoglobulin isotypes may exist and may represent a heretofore unidentified component of the immune system.


The role of mediators of cell invasiveness, motility, and migration in the pathogenesis of silent corticotroph adenomas.
Silent corticotroph adenomas (SCAs) represent a distinct subset of clinically non-functioning pituitary adenomas. There are two variants of SCA; type I are densely granulated basophilic tumors and type II are sparsely granulated and chromophobic tumors. SCAs are known to be aggressive than the more common non-functioning gonadotroph adenomas (NFGAs). Cell-matrix interactions play an important role in the pathogenesis of pituitary adenomas. In this study, we compared 19 SCAs and 50 NFGAs with known fibroblast growth factor receptor-4 (FGFR4) status using semi-quantitative immunohistochemistry to localize β1-integrin, osteopontin, and matrix metalloproteinase-1 (MMP-1) as cytoplasmic, membranous, or mixed cytoplasmic-membranous staining to achieve scores of 1-4. Staining for β1-integrin was significantly higher in SCAs (100 %, score 3.3) than in NFGAs (96 %; score 2.6) (p = 0.0482); there was no statistical difference within subgroups of SCA (type II score 3.4; type I score 2.8) (p = 0.2663). Osteopontin immunoreactivity was also higher in SCAs (100 %, score 3.7) than in NFGAs (42 %, score 0.8) (p = 0.0001); there was no statistical difference within subgroups of SCA (type II score 3.6; type I score 3.9) (p = 0.2787). In contrast, MMP-1 immunoreactivity was lower in SCAs (89 %; score 2.5) than in NFGAs (98 %; score 3.6) (p = 0.0005); there was no statistical difference within subgroups of SCA (type II score 2.7; type I score 2.0) (p = 0.30704). The MMP-1 results correlated with FGFR4 expression (NFGA 96 %, type II SCA 71 %, type I SCA 40 %). Our data indicate that the biological aggressivity of SCAs compared with NFGA may be due to high osteopontin expression; in contrast, high MMP-1 is characteristic of NFGAs that also express more FGFR4. Further investigations are warranted to clarify the underlying regulatory mechanisms of these markers. The high osteopontin or FGFR4/MMP-1 expression levels in SCAs and NFGAs, respectively, indicate the potential for therapeutic strategies targeting osteopontin or FGFR4/MMP-1 for inoperable tumors of these types.


[The role of ischemic heart disease risk factors in pathogenesis of cardiological syndrome X].
To specify lipid and carbohydrate metabolisms, coagulation and platelet hemostasis and their relationships with impairment of coronary circulation in patients with cardiological syndrome X (SX), we examined 204 SX patients and 31 controls. Compared to the controls, examinees with SX had signs of hyperinsulinemia, high levels of LDLP cholesterol, VLDLP cholesterol, atherogenic index, packed cell volume, fibrinogen and platelet aggregation. We found a positive correlation between the level of LDLP cholesterol, severity of hyperinsulinemia and maximal depression of ST wave in the course of bicycle exercise. There was no correlation between hemostasis parameters and the degree of ST depression.


[Tuberculosis morbidity trends among children, adolescents and young adults in Uzbekistan].
After a declining period by the mid-1980s and its stabilization in 1985-1995, the morbidity rates of tuberculosis in Uzbekistan increased in 1996 by 20.7% as compared to 1995, by 24% among children in the past decade, and 2 times among adolescents and young individuals aged under 30 years within 5 years. The rise of mortality rates is accompanied by aggravation of the clinical forms of the tuberculosis cases detected. The goal-oriented examinations of populations at risk of the disease in 14 districts of the Republic indicated a 1.5-fold increase in total mortality rates, followed by an upward tendency.


Some observations on the dietary vitamin D requirement of weanling pups.
A study was conducted to test the hypothesis that growing dogs do not require supplementation with cholecalciferol (vitamin D-3) in a nonpurified extruded diet. Twenty-eight weanling pups from four litters of English pointers and two litters of German Shepherd dogs were allotted equally to two groups by gender and weight. Dogs were raised in indoor-outdoor kennel runs for the 102-wk evaluation. One group was fed a diet that contained no added vitamin D while the other group was fed the same diet to which had been added 60.5 micrograms cholecalciferol/kg diet. Both diets contained approximately 14% calcium and 1.0% phosphorus. Growth as measured by body weight and length, serum calcium, phosphorus and alkaline phosphatase and urine hydroxyproline were not significantly different (P greater than 0.05) between the two treatment groups. There was no relationship between dietary treatment and nutritional secondary hyperparathyroidism (NSH), rickets or other skeletal abnormalities. The data support the concept that addition of vitamin D to typical commercial dog foods for purposes of prevention or amelioration of rickets, NSH or other skeletal diseases is unnecessary.


Quick approximation of bivariate functions.
This paper presents two experiments where participants had to approximate function values at various generalization points of a square, using given function values at a small set of data points. A representative set of standard function approximation models was trained to exactly fit the function values at data points, and models' responses at generalization points were compared to those of humans. Then one defined a large class of possible models (including the best two identified predictors) and the class maximal possible prediction accuracy was evaluated. A new model of quick multivariate function approximation belonging to this class was proposed. Its prediction accuracy was close to the maximum possible, and significantly better than that of all other models tested. The new model also provided a significant account of human response variability. Finally, it was shown that this model is more particularly suitable for problems in which the visual system can perform some specific structuring of the data space. This model is therefore considered as a suitable starting point for further investigations into quick multivariate function approximation, which is to date an inadequately explored question in cognitive psychology.


[Ribosomal proteins of Escherichia coli. Some features of the primary and three-dimensional structure].
Some properties of E. coli ribisomal proteins, e. g. molecular weights, isoelectric points, amino acid composition, are reviewed. The three-dimensional structure of the proteins in solution has been studied and the difficulties and discrepancies arising from interpretation of the results obtained have been revealed. The peculiarities of the amino acid sequences typical of the majority of the proteins or the amino acid sequences presenting unique features are interpreted in terms of the primary structure of some ribosomal proteins. The primary structure of the proteins determined with the use of interesting methodological procedures is discussed.


Dietary Quality and Ovarian Cancer Risk in African-American Women.
This study evaluated 3 index-based dietary patterns-Healthy Eating Index (HEI)-2005, HEI-2010, and Alternate Healthy Eating Index (AHEI)-2010-in relation to ovarian cancer risk in African-American women. The study was conducted among 415 ovarian cancer cases and 629 age- and site-matched controls of African-American descent recruited from the population-based African American Cancer Epidemiology Study. Multivariable unconditional logistic regression models were used to estimate odds ratios and 95% confidence intervals between quartiles of dietary quality indices and ovarian cancer risk, adjusting for potential confounders. We found that higher AHEI-2010 scores, but not HEI-2005 or HEI-2010 scores, were associated with lower risk of ovarian cancer (comparing the highest quartile (4th) vs. lowest (1st), odds ratio (OR) = 0.66, 95% confidence interval (CI): 0.45, 0.98; P for trend = 0.05). When stratified by menopausal status, no noteworthy associations were observed among premenopausal women. However, among postmenopausal women, greater adherence to HEI-2010 (quartile 4 vs. quartile 1, OR = 0.57, 95% CI: 0.36, 0.92; P for trend = 0.03) and AHEI-2010 (quartile 4 vs. quartile 1, OR = 0.49, 95% CI: 0.31, 0.78; P for trend = 0.01) were inversely associated with ovarian cancer. Our findings indicate that adherence to an overall healthy dietary pattern may reduce ovarian cancer risk in African-American women, and particularly among postmenopausal African-American women.


Practice guidelines for diseases caused by Aspergillus. Infectious Diseases Society of America.
Aspergillosis comprises a variety of manifestations of infection. These guidelines are directed to 3 principal entities: invasive aspergillosis, involving several organ systems (particularly pulmonary disease); pulmonary aspergilloma; and allergic bronchopulmonary aspergillosis. The recommendations are distilled in this summary, but the reader is encouraged to review the more extensive discussions in subsequent sections, which show the strength of the recommendations and the quality of the evidence, and the original publications cited in detail. Invasive aspergillosis. Because it is highly lethal in the immunocompromised host, even in the face of therapy, work-up must be prompt and aggressive, and therapy may need to be initiated upon suspicion of the diagnosis, without definitive proof (BIII). Intravenous therapy should be used initially in rapidly progressing disease (BIII). The largest therapeutic experience is with amphotericin B deoxycholate, which should be given at maximum tolerated doses (e.g., 1-1.5 mg/kg/d) and should be continued, despite modest increases in serum creatinine levels (BIII). Lipid formulations of amphotericin are indicated for the patient who has impaired renal function or who develops nephrotoxicity while receiving deoxycholate amphotericin (AII). Oral itraconazole is an alternative for patients who can take oral medication, are likely to be adherent, can be demonstrated (by serum level monitoring) to absorb the drug, and lack the potential for interaction with other drugs (BII). Oral itraconazole is attractive for continuing therapy in the patient who responds to initial iv therapy (CIII). Therapy should be prolonged beyond resolution of disease and reversible underlying predispositions (BIII). Adjunctive therapy (particularly surgery and combination chemotherapy, also immunotherapy), may be useful in certain situations (CIII). Aspergilloma. The optimal treatment strategy for aspergilloma is unknown. Therapy is predominantly directed at preventing life-threatening hemoptysis. Surgical removal of aspergilloma is definitive treatment, but because of significant morbidity and mortality it should be reserved for high-risk patients such as those with episodes of life-threatening hemoptysis, and considered for patients with underlying sarcoidosis, immunocompromised patients, and those with increasing Aspergillus-specific IgG titers (CIII). Surgical candidates would need to have adequate pulmonary function to undergo the operation. Bronchial artery embolization rarely produces a permanent success, but may be useful as a temporizing procedure in patients with life-threatening hemoptysis. Endobronchial and intracavitary instillation of antifungals or oral itraconazole may be useful for this condition. Since the majority of aspergillomas do not cause life-threatening hemoptysis, the morbidity and cost of treatment must be weighed against the clinical benefit. Allergic bronchopulmonary aspergillosis (APBA). Although no well-designed studies have been carried out, the available data support the use of corticosteroids for acute exacerbations of ABPA (AII). Neither the optimal corticosteroid dose nor the duration of therapy has been standardized, but limited data suggest the starting dose should be approximately 0.5 mg/kg/d of prednisone. The decision to taper corticosteroids should be made on an individual basis, depending on the clinical course (BIII). The available data suggest that clinical symptoms alone are inadequate to make such decisions, since significant lung damage may occur in asymptomatic patients. Increasing serum IgE levels, new or worsening infiltrate on chest radiograph, and worsening spirometry suggest that corticosteroids should be used (BII). Multiple asthmatic exacerbations in a patient with ABPA suggest that chronic corticosteroid therapy should be used (BIII). Itraconazole appears useful as a corticosteroid sparing agent (BII). (ABSTRACT TRUNCATED)


Chitin or chitin-like glycans as targets for late-term cancer chemoprevention.
A consistent observation in studies of carcinogenesis is that some glycans are expressed differently in cancer cells than in normal cells. A well-known example is the aberrant β1-6 N-acetyl-d-glucosamine branching associated with metastasis and poor prognosis in many cancers. This commentary proposes that, although not found in normal mammalian cells, a chitin (β-1,4-linked N-acetyl-d-glucosamine) or a chitin-like polysaccharide (e.g., hyaluronan) may exist as a cancer-associated glycan, which can be targeted by the novel pyrimidine nucleotide derivative SP-1015 (designed as a chitin synthase inhibitor). Preliminary chemoprevention data of our group showed SP-1015 in the diet can inhibit benzo(a)pyrene-induced neoplasia in the forestomach of female A/J mice, and, of importance, this activity occurred at late stages in carcinogenesis. While no effect was seen in the murine lung, this may be due to the low bioavailability of the compound. A different route of administration (e.g. inhalation of an aerosol) may have potential to inhibit pulmonary carcinogenesis. We hypothesize that inhibitors of chitin or chitin-like glycan formation may be effective chemopreventive agents and suggest that further work is needed to study these novel targets for cancer prevention.


[Shortening undergraduate medical training: now and for all medical schools in Chile?].
In Chile, undergraduate medical education starts after High School, it lasts seven years, with the final two dedicated to a rotary internship, taking to an M.D. degree that allows the graduate to enter working activities. The country needs more M.D.s in primary care, but there is also a shortage of specialists, mainly out of the main cities. In recent decades, post graduate programs leading to specialty titles have become competitively adopted by a large proportion of medical graduates. This is the case at the Pontificia Universidad Católica de Chile, stimulating its faculties and medical students to develop a collaborative review of their teaching programs, leading to a curricular reform with a new graduate profile and a new curriculum oriented to learning objectives, that will allow to obtain the M.D. degree in six instead of seven years of undergraduate education. This new program awakened expectations in other universities in Chile, that will have to face the attraction of this shortened program for future candidates to enter medical schools. However, any shortening of medical school careers should first consider the local conditions in quality of applicants, number of accepted students, the training of teachers in integrated teaching programs, the availability of adequate campuses. Furthermore, for students with different academic backgrounds and diverse personal and familial interests, the seven years programs may still be necessary to gain the expertise required to become medical doctors.


Immunomodulatory Protective Effects of Nigella sativa and Lactuca sativa Oils on Liver Intoxication in Experimental Animals.
Background and Objective: The liver plays an important role in transforming and clearing chemicals in human body. Hepatic injury is usually caused by numerous toxic chemicals such as carbon tetrachloride, thioacetamide, galactosamine and drugs including paracetamol as overdoses consumption. This investigation aimed to study the immunomodulatory protective effects of black seed (Nigella sativa L.) oil and lettuce (Lactuca sativa L.) oil against paracetamol liver intoxication in rats. Materials and Methods: Twenty-four male albino rats weighing 150±10 g each, were randomly divided into 4 equal groups (6 rats each) as follows: Control negative; control positive as paracetamol hepatotoxicity; Nigella sativa oil and Lactuca sativa oil at a dose of 1 mL kg1 b.wt., as protective from hepatotoxicity, then serum analysis for all rats were conducted and the obtained data were analyzed using SPSS version-22. Results: All rats orally preventable injected with Nigella sativa and Lactuca sativa oils caused significant decrease in Unsaturated Iron Binding Capacity (UIBC), creatine kinase (CK), Creatine Kinase-MB (CKMB), magnesium (Mg), phosphor (Phos.), iron (Fe), sodium (Na), potassium (K), amylase (Amyl), tri-glycerides (TG), total cholesterol (TC), Low Density Lipoprotein (LDL), creatinine (Creat), Lactate Dehydrogenase (LDH) as compared to liver intoxicated rats. Conclusion: Black seed oils and Lactuca sativa oils could be used as natural immunomodulatory agents against paracetamol liver intoxication and enhance the body's immune functions with improving the health status of the liver.


Changes in histone methylation and acetylation during microspore reprogramming to embryogenesis occur concomitantly with Bn HKMT and Bn HAT expression and are associated with cell totipotency, proliferation, and differentiation in Brassica napus.
In response to stress treatments, microspores can be reprogrammed to become totipotent cells that follow an embryogenic pathway producing haploid and double-haploid embryos which are important biotechnological tools in plant breeding. Recent studies have revealed the involvement of DNA methylation in regulating this process, but no information is available on the role of histone modifications in microspore embryogenesis. Histone modifications are major epigenetic marks controlling gene expression during plant development and in response to environmental changes. Lysine methylation of histones, accomplished by histone lysine methyltransferases (HKMTs), can occur on different lysine residues, with histone H3K9 methylation being mainly associated with transcriptionally silenced regions. In contrast, histone H3 and H4 acetylation is carried out by histone acetyltransferases (HATs) and is associated with actively transcribed genes. In this work, we analyzed 3 different histone epigenetic marks: dimethylation of H3K9 (H3K9me2) and acetylation of H3 and H4 (H3Ac and H4Ac) during microspore embryogenesis in Brassica napus by Western blot and immunofluorescence assays. The expression patterns of histone methyltransferase BnHKMT and histone acetyltransferase BnHAT genes have also been analyzed by qPCR. Our results revealed different spatial and temporal distribution patterns for methylated and acetylated histone variants during microspore embryogenesis and their similarity with the expression profiles of BnHKMT and BnHAT, respectively. The data presented suggest the participation of H3K9me2 and HKMT in embryo cell differentiation and heterochromatinization events, whereas H3Ac, H4Ac, and HAT would be involved in transcriptional activation, totipotency, and proliferation events during cell reprogramming and embryo development.


The rectus abdominis free flap in head and neck reconstruction.
The rectus abdominis musculocutaneous free flap, based on the deep inferior epigastric artery and vein, has been used widely in reconstruction of the breast and extremities. The number of reports on its applications in the head and neck is limited. The rectus abdominis free flap is one of the most versatile soft-tissue flaps. The deep inferior epigastric artery and vein are long, large-diameter vessels that are ideal for microvascular anastomoses. The area of skin that can be transferred is probably the largest of all flaps presently in use. The versatility of this donor site is due to the ability to transfer large areas of skin with varying thicknesses and varying amounts of underlying muscle. We have successfully used this flap in 15 consecutive patients to reconstruct defects of the neck, face, mouth, pharynx, skull base, and scalp. No major complications involving either the recipient or donor sites occurred. The literature on the use of the rectus abdominis flap in head and neck reconstruction is reviewed in detail. The advantages and disadvantages of this soft-tissue free flap are thoroughly discussed in an effort to better define its proper place among the reconstructive options available to the head and neck surgeon.


University - industry collaborations: models, drivers and cultures.
The way academic institutions and pharmaceutical companies have been approaching collaborations has changed significantly in recent years. A multitude of interaction models were tested and critical factors that drive successful collaborations have been proposed. Based on this experience the current consensus in the pharmaceutical industry is to pursue one of two strategies: an open innovation approach to source discoveries wherever they occur, or investing selectively into scientific partnerships that churn out inventions that can be translated from bench to bedside internally. While these strategies may be intuitive, to form and build sustainable relationships between academia and large multinational healthcare enterprises is proving challenging. In this article we explore some of the more testing aspects of these collaborations, approaches that various industrial players have taken and provide our own views on the matter. We found that understanding and respecting each other's organisational culture and combining the intellectual and technological assets to answer big scientific questions accelerates and improves the quality of every collaboration. Upon discussing the prevailing cooperation models in the university - industry domain, we assert that science-driven collaborations where risks and rewards are shared equally without a commercial agenda in mind are the most impactful.


Buffering Internalization of HIV Stigma: Implications for Treatment Adherence and Depression.
One mechanism through which social stigma of HIV affects health outcomes for people living with HIV (PLWH) is through internalization of stigma. However, this transformation of social stigma in the community into internalized stigma may not be of the same magnitude for all PLWH. We examined the moderating effects of 3 personality traits-fear of negative social evaluation, attachment-related anxiety, and dispositional resilience-in transforming perceived stigma in the community into internalized stigma. Furthermore, we investigated downstream effects of these moderated associations on depressive symptoms and antiretroviral treatment (ART) adherence. In study 1, data from 203 PLWH in the Southeast United States were analyzed controlling for age, sex, education, race, and time on ART. In study 2, data from 453 women in a multisite study were analyzed controlling for age, education, race, time on ART, and substance use. In both studies, fear of negative evaluation and attachment-related anxiety moderated the effect of perceived HIV stigma in the community on internalized HIV stigma: People higher on those moderating variables had stronger associations between perceived stigma in the community and internalized stigma. In study 2, resilience was assessed and also moderated the effect of perceived HIV stigma in the community on internalized stigma. In moderated mediation models, fear of negative evaluation, attachment-related anxiety, and resilience moderated the indirect effect of perceived HIV stigma in the community on ART adherence and depression through internalized stigma. Interventions to assuage internalization of HIV stigma should focus on bolstering attachment-related security, social competence, and resilience.


SetupX--a public study design database for metabolomic projects.
Metabolomic databases are useless without accurate description of the biological study design and accompanying metadata reporting on the laboratory workflow from sample preparation to data processing. Here we report on the implementation of a database system that enables investigators to detail and set up a biological experiment, and that also steers laboratory workflows by direct access to the data acquisition instrument. SetupX utilizes orthogonal biological parameters such as genotype, organ, and treatment(s) for delineating the dimensions of a study which define the number of classes under investigation. Publicly available taxonomic and ontology repositories are utilized to ensure data integrity and logic consistency of class designs. Class descriptions are subsequently employed to schedule and randomize data acquisitions, and to deploy metabolite annotations carried out by the seamlessly integrated mass spectrometry database, BinBase. Annotated result data files are housed by SetupX for downloads and queries. Currently, 39 users have generated 48 studies, some of which are made public.


Protein translocation channel of mitochondrial inner membrane and matrix-exposed import motor communicate via two-domain coupling protein.
The majority of mitochondrial proteins are targeted to mitochondria by N-terminal presequences and use the TIM23 complex for their translocation across the mitochondrial inner membrane. During import, translocation through the channel in the inner membrane is coupled to the ATP-dependent action of an Hsp70-based import motor at the matrix face. How these two processes are coordinated remained unclear. We show here that the two domain structure of Tim44 plays a central role in this process. The N-terminal domain of Tim44 interacts with the components of the import motor, whereas its C-terminal domain interacts with the translocation channel and is in contact with translocating proteins. Our data suggest that the translocation channel and the import motor of the TIM23 complex communicate through rearrangements of the two domains of Tim44 that are stimulated by translocating proteins.


Functional limitations of people with rheumatoid arthritis or axial spondyloarthritis and severe functional disability: a cross-sectional descriptive study.
The objective of the study is to describe the nature of functional limitations in activities and participation in people with Rheumatoid Arthritis (RA) or axial SpondyloArthritis (axSpA) with severe functional disability. Baseline data from people with RA (n = 206) or axSpA (n = 155) and severe functional disability participating in an exercise trial were used. Their three most limited activities were derived from the Patient Specific Complaint (PSC) instrument and linked to the International Classification of Functioning and Health (ICF). The frequencies of ICF categories were calculated and compared with Activities and Participation items of the ICF Core Sets for RA (32 second-level categories) and Ankylosing Spondylitis (AS) (24 second-level categories). In total 618 and 465 PSC activities were linked to 909 (72 unique in total; 25 unique second-level) and 759 (57 unique in total; 23 unique second-level) ICF categories in RA and axSpA. Taking into account all three prioritized activities, the five most frequent limited activities concerned the ICF chapter "Mobility", and included "Walking" (RA and axSpA 2 categories), "Changing basic body position" (RA and axSpA 1 category), "Stair climbing"(RA) and "Grasping" (RA),"Lifting" (axSpA) and "Maintaining a standing position" (axSpA). In RA, 21/32 (66%) and in axSpA 14/24 (58%) unique second-level categories identified in the prioritized activities are present in the Comprehensive Core Sets. Most limitations of people with RA or axSpA and severe functional disability were seen in the ICF chapter "Mobility". Most of the identified ICF categories were covered by the corresponding items of the ICF RA and AS Core Sets.


Visual gene developer: a fully programmable bioinformatics software for synthetic gene optimization.
Direct gene synthesis is becoming more popular owing to decreases in gene synthesis pricing. Compared with using natural genes, gene synthesis provides a good opportunity to optimize gene sequence for specific applications. In order to facilitate gene optimization, we have developed a stand-alone software called Visual Gene Developer. The software not only provides general functions for gene analysis and optimization along with an interactive user-friendly interface, but also includes unique features such as programming capability, dedicated mRNA secondary structure prediction, artificial neural network modeling, network & multi-threaded computing, and user-accessible programming modules. The software allows a user to analyze and optimize a sequence using main menu functions or specialized module windows. Alternatively, gene optimization can be initiated by designing a gene construct and configuring an optimization strategy. A user can choose several predefined or user-defined algorithms to design a complicated strategy. The software provides expandable functionality as platform software supporting module development using popular script languages such as VBScript and JScript in the software programming environment. Visual Gene Developer is useful for both researchers who want to quickly analyze and optimize genes, and those who are interested in developing and testing new algorithms in bioinformatics. The software is available for free download at http://www.visualgenedeveloper.net.


Glucoregulatory and metabolic response to exercise in obese noninsulin-dependent diabetes.
The metabolic response to exercise in obese postabsorptive noninsulin-dependent diabetics was compared to that of obese nondiabetics. Exercise consisted of 45 min on a cycle ergometer at 60% maximum oxygen consumption. Six diabetic subjects were studied during oral hypoglycemic therapy and four on diet alone. The sulfonylurea therapy had no effect on the response. Glycemia was elevated at rest in both diabetic subgroups (192 +/- 24 mg/dl for diet alone, 226 +/- 36 mg/dl for sulfonylurea treatment) and a similar fall (35 and 37 mg/dl, respectively) occurred with exercise. In control subjects, glycemia was 86 +/- 4 mg/dl and did not change with exercise. In the diabetics at rest, glucose production was elevated (220 +/- 25 mg/min), whereas the metabolic clearance of glucose was suppressed. During exercise the increase in glucose utilization was similar to that in controls, but glucose production failed to increase significantly, thus accounting for the decline in plasma glucose. At rest, plasma immunoreactive insulin (IRI) was elevated to 0.90 ng/ml in the controls and decreased to 0.65 ng/ml with exercise. In the diabetics IRI was similarly elevated (0.89 ng/ml) but failed to decrease normally with exercise. Lactate, pyruvate, alanine, and free fatty acids increased similarly in diabetics and controls, whereas the increase in 3-hydroxybutyrate during recovery was less in diabetics. The sustained insulinemia, the basal overproduction of glucose, and hyperglycemia itself may all contribute to the observed differences in glucose flux during exercise in noninsulin-dependent diabetics.


[Assessment of the optical image quality of the eye using raytracing technique of corneal topography data].
Optical aberrations in the optical system may downgrade image quality and cannot be fully compensated by spherocylindrical glasses. The subjectively evaluated visual acuity may be significantly reduced. The purpose of this study was to calculate the image forming properties of the eye using a spotlight source or alternatively extended objects. A convex and first derivative continuous (C1) surface from the rough height data of the anterior corneal surface (TMS-1, Tomey, Erlangen) or the anterior and posterior corneal surface (Orbscan, Orbtec, USA) was calculated by means of an interpolating subdivision scheme (modified Butterfly algorithm). The characteristics of the residual refractive surfaces were used according to Navarro's eye model. The focal distance was calculated from the exact raytracing calculation (Snellius' law) of the point-spread function by minimising the variance of the point-spread function. The diffraction property of the aperture stop was implemented with a transmission characteristic according to a radially symmetrical Bessel function within the entrance pupil. The algorithm was realised with a C code on the LINUX platform and applied to a normal eye (example 1, TMS-1), an eye with severe keratoconus (example 2, TMS-1) and an eye with corneal scars (example 3, Orbscan). The focal distance in example 1 (22.5 mm, 22.6 mm, and 22.8 mm) increased with the pupil diameter (2 mm, 3 mm, and 5 mm). The variance of the approximately radially symmetrical point-spread function in the focal plane attained a minimum value with a pupil size of 3 mm (0.164, 0.104, and 0.230). In example 2, the focal distance changed inconclusively (21.1 mm, 21.0 mm, and 21.3 mm) with the pupil size (2 mm, 3 mm, and 5 mm). The variance of the markedly asymmetrical point-spread function in the focal plane was systematically higher compared to the values of example 1 and reached a minimum value with a pupil size of 3 mm (0.255, 0.224, and 0.371). The imaging of the sinus-modulated pattern is anisotropic due to the asymmetry of the point-spread function. In example 3, the focal distance (22.3 mm, 22.3 mm, and 22.5 mm) did not change systematically with the pupil size (2 mm, 3 mm, and 5 mm). The variance of the nearly radially symmetrical point-spread function changed only marginally between pupil sizes of 2 mm and 3 mm (0.231, 0.239, and 0.338). Raytracing of corneal topography height data based on refined eye models with the option of auto-focussing has the potential to trace the optical resolution of the eye for arbitrary objects. Further studies on contrast sensitivity and the conversion of the real image to a perceived image by the retina and brain are required for complete modeling of subjective visual acuity.


A hidden cost of migration? Innate immune function versus antioxidant defense.
Migration is energetically demanding and physiologically challenging. Migrating birds, for example, need to boost their antioxidant defenses to defeat the pro-oxidants produced during high energetic activity. The enhanced antioxidant defense possibly withdraws limited resources (e.g., energy or micronutrients) from other physiological functions, such as immune defense. Such a trade-off might not occur outside the migration seasons or in resident individuals. Here, we investigate whether there is a negative relationship between innate immune function and antioxidant defense by sampling both migrating and resident blackbirds (Turdus merula) at the same location during the same period of the annual cycle. We show that in migrating blackbirds microbial killing capacity (BKA), an integrative measure of baseline innate immune function was negatively correlated with total nonenzymatic antioxidant capacity. In contrast, in resident conspecifics, sampled at the same time and location, these two physiological measures were not correlated. This suggests that migrating birds trade off innate immune function and antioxidant defense. Furthermore, and likely a consequence of this trade-off, in migrant blackbirds BKA was positively correlated with oxidative damage to lipids. In resident blackbirds BKA and degree of lipid oxidation were uncorrelated. The mechanism and currencies of the supposed trade-off are currently unknown, but energetic investments or micronutrients are likely candidates. Future experimental studies could provide more conclusive evidence for this trade-off; yet, our results open up a new level of thinking about the physiological costs of migration.


Measurement of the t t ¯ production cross section, the top quark mass, and the strong coupling constant using dilepton events in pp collisions at s = 13 Te .
A measurement of the top quark-antiquark pair production cross section σ t t ¯ in proton-proton collisions at a centre-of-mass energy of 13 Te is presented. The data correspond to an integrated luminosity of 35.9 fb - 1 , recorded by the CMS experiment at the CERN LHC in 2016. Dilepton events ( e ± μ ∓ , μ + μ - , e + e - ) are selected and the cross section is measured from a likelihood fit. For a top quark mass parameter in the simulation of m t MC = 172.5 Ge the fit yields a measured cross section σ t t ¯ = 803 ± 2 (stat) ± 25 (syst) ± 20 (lumi) pb , in agreement with the expectation from the standard model calculation at next-to-next-to-leading order. A simultaneous fit of the cross section and the top quark mass parameter in the powheg simulation is performed. The measured value of m t MC = 172.33 ± 0.14 (stat) - 0.72 + 0.66 (syst) Ge is in good agreement with previous measurements. The resulting cross section is used, together with the theoretical prediction, to determine the top quark mass and to extract a value of the strong coupling constant with different sets of parton distribution functions.


Tibial Nerve Stimulation for Treating Neurogenic Lower Urinary Tract Dysfunction: A Systematic Review.
Tibial nerve stimulation (TNS) is a promising therapy for non-neurogenic lower urinary tract dysfunction and might also be a valuable option for patients with an underlying neurological disorder. We systematically reviewed all available evidence on the efficacy and safety of TNS for treating neurogenic lower urinary tract dysfunction (NLUTD). The review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement. After screening 1943 articles, 16 studies (4 randomized controlled trials [RCTs], 9 prospective cohort studies, 2 retrospective case series, and 1 case report) enrolling 469 patients (283 women and 186 men) were included. Five studies reported on acute TNS and 11 on chronic TNS. In acute and chronic TNS, the mean increase of maximum cystometric capacity ranged from 56 to 132mL and from 49 to 150mL, and the mean increase of bladder volume at first detrusor overactivity ranged from 44 to 92mL and from 93 to 121mL, respectively. In acute and chronic TNS, the mean decrease of maximum detrusor pressure during the storage phase ranged from 5 to 15cm H2O and from 4 to 21cm H2O, respectively. In chronic TNS, the mean decrease in number of voids per 24h, in number of leakages per 24h, and in postvoid residual ranged from 3 to 7, from 1 to 4, and from 15 to 55mL, respectively. No TNS-related adverse events have been reported. Risk of bias and confounding was high in most studies. Although preliminary data of RCTs and non-RCTs suggest TNS might be effective and safe for treating NLUTD, the evidence base is poor, derived from small, mostly noncomparative studies with a high risk of bias and confounding. More reliable data from well-designed RCTs are needed to reach definitive conclusions. Early data suggest tibial nerve stimulation might be effective and safe for treating neurogenic lower urinary tract dysfunction, but more reliable evidence is required.


Liver is a target of arsenic carcinogenesis.
Inorganic arsenic is clearly a human carcinogen causing tumors of the skin, lung, urinary bladder, and possibly liver (IARC, 2004). At the time of construction of this monograph, the evidence for arsenic as a hepatocarcinogen in humans was considered controversial and in rodents considered insufficient. However, recent data has accumulated indicating hepatocarcinogenicity of arsenic. This forum reevaluates epidemiology studies, rodent studies together with in vitro models, and focuses on the liver as a target organ of arsenic toxicity and carcinogenesis. Hepatocellular carcinoma and hepatic angiosarcoma, have been frequently associated with environmental or medicinal exposure to arsenicals. Preneoplastic lesions, including hepatomegaly, hepatoportal sclerosis, fibrosis, and cirrhosis often occur after chronic arsenic exposure. Recent work in mice clearly shows that exposure to inorganic arsenic during gestation induces tumors, including hepatocellular adenoma and carcinoma, in offspring when they reach adulthood. In rats, the methylated arsenicals, dimethylarsinic acid promotes diethylnitrosamine-initiated liver tumors, whereas trimethylarsine oxide induces liver adenomas. Chronic exposure of rat liver epithelial cells to low concentrations of inorganic arsenic induces malignant transformation, producing aggressive, undifferentiated epithelial tumors when inoculated into the Nude mice. There are a variety of potential mechanisms for arsenical-induced hepatocarcinogenesis, such as oxidative DNA damage, impaired DNA damage repair, acquired apoptotic tolerance, hyperproliferation, altered DNA methylation, and aberrant estrogen signaling. Some of these mechanisms may be liver specific/selective. Overall, accumulating evidence clearly indicates that the liver could be an important target of arsenic carcinogenesis.


Slowly varying function method applied to quartz crystal oscillator transient calculation.
By using an approach based on the full nonlinear Barkhausen criterion, it is possible to describe oscillator behavior under the form of a nonlinear characteristic polynomial whose coefficients are functions of the circuit components and of the oscillation amplitude. Solving the polynomial in the frequency domain leads to the steady state oscillation amplitude and frequency. In the time domain, the characteristic polynomial represents a nonlinear differential equation whose solution gives the oscillator signal transient. It is shown how symbolic manipulation capabilities of commercially available softwares can be used to automatically generate the coding of the oscillator characteristic polynomial from the SPICE description netlist. The numerical processing of such an equation in the time domain leads to unacceptable computer time because of the high quality factor of the oscillator circuits involved. Nevertheless, by using the slowly varying amplitude and phase method, it is possible to transform the initial nonlinear differential equation into a nonlinear first order differential equation system in the amplitude and phase variables. The solution of this system directly gives the designer the most relevant features of the oscillation; that is, the amplitude, phase, or frequency transients which can be accurately obtained within a short computer time by using classical numerical algorithms.


Use of anteroposterior view fluoroscopy for targeting percutaneous pedicle screws in cases of spinal deformity with axial rotation.
Over the past decade percutaneous pedicle screws have become popular for the minimally invasive treatment of spinal disorders. However, until the last 5 years the presence of a significant spinal deformity was regarded as a relative contraindication for percutaneous instrumentation. Recent advances in surgical technique and intraoperative technology have made percutaneous fixation in complex spinal pathologies more commonplace. The authors report their experience using a parsimonious method for uniplanar fluoroscopic targeting of pedicles in challenging cases. The authors performed a retrospective analysis of patients with adult spinal deformity who underwent percutaneous pedicle screw instrumentation from 2008 to 2013. Cases were included if a spiral slice postoperative CT scan was obtained. All cases had a minimum of 10° of axial rotation and typically had additional accompanying anatomical abnormalities. Screws were assessed for any pedicle violations as well as any impingement of the surrounding facet joints. A total of 410 pedicle screws were placed in 36 patients with an average 6.4 levels of instrumentation per patient. The mean age was 67 years (range 44-86 years) and there were 25 females. Of the 410 screws, 29 (7.1%) had some medial or lateral pedicle violation. Of these, 15 (3.7%) were Grade 1, 6 (1.4%) were Grade 2, and 8 (2.0%) were Grade 3 violations. Of the Grade 3 violations, 2 each were at the L-4, L-5, and S-1 levels, and 1 each was at the T-10 and L-1 levels. Two of the patients had symptoms and both underwent screw repositioning, one during the same admission and the other in a delayed fashion. Both were at the L-5 and S-1 levels with anatomically highly medialized pedicles. There were no motor deficits, and both removals were for numbness. Of the 72 screws at the proximal end of the construct, there were 6 facet violations (8.3%). Four (5.6%) of these were Grade 1, 1 (1.4%) was Grade 2, and 1 (1.4%) was Grade 3. The anteroposterior fluoroscopic technique can be effectively used by spinal surgeons to cannulate the pedicles in patients with rotational deformities. The complication rate in this challenging population is acceptable and is in accordance with the existing literature. However, caution should be used at L-5 and S-1 when the pedicle is narrow and highly medialized, rendering an indistinct medial wall on anteroposterior imaging.


Isotopic evidence for geographic heterogeneity in Ancient Greek military forces.
Increased mobility and human interactions in the Mediterranean region during the eighth through fifth centuries BCE resulted in heterogeneous communities held together by political and cultural affiliations, periodically engaged in military conflict. Ancient historians write of alliances that aided the Greek Sicilian colony Himera in victory against a Carthaginian army of hired foreign mercenaries in 480 BCE, and the demise of Himera when it fought Carthage again in 409 BCE, this time unaided. Archaeological human remains from the Battles of Himera provide unique opportunities to test early written history by geochemically assessing the geographic origins of ancient Greek fighting forces. We report strontium and oxygen isotope ratios of tooth enamel from 62 Greek soldiers to evaluate the historically-based hypothesis that a coalition of Greek allies saved Himera in 480 BCE, but not in 409 BCE. Among the burials of 480 BCE, approximately two-thirds of the individuals are non-local, whereas among the burials of 409 BCE, only one-quarter are non-local, in support of historical accounts. Although historical accounts specifically mention Sicilian Greek allies aiding Himera, isotopic values of many of the 480 BCE non-locals are consistent with geographic regions beyond Sicily, suggesting Greek tyrants hired foreign mercenaries from more distant places. We describe how the presence of mercenary soldiers confronts prevailing interpretations of traditional Greek values and society. Greek fighting forces reflect the interconnectedness and heterogeneity of communities of the time, rather than culturally similar groups of neighbors fighting for a common cause, unified by "Greekness," as promoted in ancient texts.


Agenda setting in psychiatric consultations: an exploratory study.
Patient- or consumer-centeredness has been recognized as a critical component of quality in primary health care, but is only beginning to be recognized and studied in mental health. Among the first opportunities to be consumer-centered is collaboratively producing an agenda of topics to be covered during a clinic visit. Early agenda setting sets the stage for what is to come and can affect the course, direction, and quality of care. The purpose of this work is to study agenda setting practices among 8 prescribers (5 psychiatrists and 3 nurse practitioners) at the beginning of their encounters with 124 consumers diagnosed with schizophrenia spectrum disorders (56%), bipolar disorder (23%), major depression (15%), and other disorders (6%). We modified an extant agenda-setting rubric by adding behaviors identified by a multidisciplinary team who iteratively reviewed transcripts of the visit openings. Once overall consensus was achieved, two research assistants coded all of the transcripts. Twenty-five transcripts were scored by both raters to establish interrater reliability. We identified 10 essential elements of agenda setting. Almost 10% of visits had no agenda set, and only 1 of 3 encounters had partial or complete elicitation of a single concern. Few additional concerns (4%) were solicited, and no encounter contained more than 6 essential elements. Collaborative agenda setting represents a unique opportunity to translate the concept of consumer-centeredness into mental health care. Initial results suggest the rating system is reliable, but the essential elements are not being used in practice.


Socio-demographic Risk Factors Associated with HIV Infection In Patients Seeking Medical Advice in a Rural Hospital of India.
Despite the fact that two thirds of HIV infected people in India are rural residents, risk factors associated with HIV infection in rural areas are not well known. In this study we have collected socio-demographic data of 6406 patients who were tested for HIV infection in a rural hospital of India and we have investigated risk factors associated with HIV. In women the most important risk factor was being a widow and the risk was higher in younger than in older widows. Other variables found to be associated with HIV infection were age between 25 and 45 years in men, low education level (especially those who only completed primary education) and working in a field not related to agriculture in scheduled castes and men from scheduled tribes. The results of this study express the need for HIV screening of widows who live in rural areas of Indian States with high HIV prevalence.


[Removable partial denture. A variation on the gauge used in design].
In this article we describe a modification of the gauge of the surveyor in such a way that we can measure the height of the retention arms' slide area over the abutment teeth, in order to obtain the same height in the reciprocal arm slide area to avoid the jiggle movements of the abutment teeth during the removal and insertion.


Transient systemic inflammation does not alter the induction of tolerance to gastric autoantigens by migratory dendritic cells.
It has been proposed that activation of dendritic cells (DCs) presenting self-antigens during inflammation may lead to activation of autoreactive T cells and the development of autoimmunity. To test this hypothesis, we examined the presentation of the autoantigen recognized in autoimmune gastritis, gastric H(+)/K(+) ATPase, which is naturally expressed in the stomach and is constitutively presented in the stomach-draining lymph nodes. Systemic administration to mice of the TLR9 agonist CpG DNA, agonist anti-CD40 Ab, or TLR4 agonist LPS all failed to abrogate the process of peripheral clonal deletion of H(+)/K(+) ATPase-specific CD4 T cells or promote the development of autoimmune gastritis. We demonstrated that migratory DCs from the stomach-draining lymph nodes are the only DC subset capable of constitutively presenting the endogenous gastric H(+)/K(+) ATPase autoantigen in its normal physiological context. Analysis of costimulatory molecules indicated that, relative to resident DCs, migratory DCs displayed a partially activated phenotype in the steady state. Furthermore, migratory DCs were refractory to stimulation by transient exposure to TLR agonists, as they failed to upregulate costimulatory molecules, secrete significant amounts of inflammatory cytokines, or induce differentiation of effector T cells. Together, these data show that transient systemic inflammation failed to break tolerance to the gastric autoantigen, as migratory DCs presenting the gastric autoantigen remain tolerogenic under such conditions, demonstrating the robust nature of peripheral tolerance.


Leukotriene B4 is a potent and stereospecific stimulator of neutrophil chemotaxis and adherence.
We studied the effects of leukotrienes on in vitro functions of neutrophil polymorphonuclear (PMN) granulocytes. Leukotriene B4 (LTB4) evoked a stimulated and directed migration of neutrophils under agarose with an optimum concentration of 10(-6)M, whereas two nonenzymatically formed isomers (compounds I and II) induced this response at 10(-5)M. Leukotriene C4 (LTC4) and 5-hydroxyeicosate-traenoic acid (5-HETE) did not affect this PMN migration. At the same optimum concentrations, LTB4 and compounds I and II augmented PMN adherence to nylon fibers. The chemotactic and adherence responses were of the same magnitude as with formal-Met-Leu-Phe (fMLP) at 10(-7)M. None of the leukotrienes influenced the spontaneous or phagocytosis-associated chemiluminescence or the ability to kill Staphylococcus aures. The cyclooxygenase inhibitor, indomethacin, inhibited only partly the fMLP-induced migration at high concentrations and stimulated migration at 2.5 x 10(-7)M, suggesting that arachidonic acid was then mainly metabolized by the lipoxygenase pathways. The lipoxygenase and cyclooxygenase inhibitor, eicosatetraynoic acid, inhibited both spontaneous and stimulated migration at greater or equal to 2.5 x 10(-5)M, but not at lower concentrations. Thus, since LTB4, and to a lesser degree compounds I and II, stimulated migration and adhesion, it is suggested that these mediators could be of importance for the emigration of neutrophils from blood vessels to areas of inflammation.


The effect of intradermal administration of inactive platelet-rich plasma on flap viability in rats.
To evaluate the effect of inactive form of platelet rich plasma (PRP) on the flap viability. Thirty six rats were used. Rats were divided into six groups then 9x3 cm random pattern skin flaps were elevated from dorsum of all rats. For precluding vascularization from the base, a silicone layer was placed under the flap in groups 2(only flap+silicone), 4(saline+silicone) and 6(PRP+silicone). In groups 1(only flap), 2(only flap+silicone) nothing was done except flap surgery. In groups 3(saline) and 4(saline+silicone), saline was applied intradermally , in groups 5(PRP) and 6(PRP+silicone), inactive form of PRP which obtained from different 16 rats was applied intradermally, into certain points of flaps immediately after surgery. After 7 days flap necrosis ratio was measured in all groups. Mean necrosis rate in group 5(PRP) (16.05%) was statistically significantly lower than group 1(only flap) (31,93%) and group 3(saline) (30,43%) (p<0.001). Mean necrosis rate in group 6(PRP+silicone) (36.37%) was statistically significantly lower than group 2(only flap+silicone) (47.93%) and group 4(saline+silicone) (45.65%) (p<0.001). Intradermal inactive platelet rich plasma administration decreases flap necrosis so for skin application.


Bears "Count" Too: Quantity Estimation and Comparison in Black Bears (Ursus Americanus).
Studies of bear cognition are notably missing from the comparative record despite bears' large relative brain size and interesting status as generalist carnivores facing complex foraging challenges, but lacking complex social structures. We investigated the numerical abilities of three American black bears (Ursus Americanus) by presenting discrimination tasks on a touch-screen computer. One bear chose the larger of two arrays of dot stimuli, while two bears chose the smaller array of dots. On some trials the relative number of dots was congruent with the relative total area of the two arrays. On other trials number of dots was incongruent with area. All of the bears were above chance on trials of both types with static dots. Despite encountering greater difficulty with dots that moved within the arrays, one bear was able to discriminate numerically larger arrays of moving dots, and a subset of moving dots from within the larger array, even when area and number were incongruent. Thus, although the bears used area as a cue to guide responding, they were also able to use number as a cue. The pattern of performance was similar to that found previously with monkeys, and suggests that bears may also show other forms of sophisticated quantitative abilities.


Vitamin D supplementation in young children: associations with Theory of Planned Behaviour variables, descriptive norms, moral norms and habits.
In the Netherlands, a supplementation of 10 microg vitamin D is recommended for children (aged 0-4 years), given that vitamin D contributes to the development of healthy bones and deficiency during childhood is a risk factor for osteoporosis at a later age. However, only 60 % of the Dutch children receive sufficient vitamin D supplementation a day. In order to develop interventions to improve supplementation intake, it is necessary to gain insight into the behaviour of parents in giving their children vitamin D supplementation and its association with variables of the Theory of Planned Behaviour, moral and descriptive norms and habits. A cross-sectional survey to assess present supplementation-related behaviour, knowledge, received information, intention, attitude, subjective norm, perceived behavioural control, moral norm, descriptive norm and habit. Data obtained from a representative Internet Panel by means of electronic questionnaires. Parents (n 270) of children aged 0-4 years. Half of the parents (48.9 %) gave their child sufficient vitamin D supplementation. Giving the supplement at a fixed time, a positive intention and habit were significantly associated with actual behaviour. The higher age of the child, first-born status, a fixed time for taking vitamin supplementation, descriptive norm and moral obligation were significantly associated with intention. These results indicate that because many parents do not give their children adequate vitamin D supplementation, the promotion of supplementation during the first years of life is a necessity. Effective yet simple strategies should be developed, focused on improving moral obligation, descriptive norms and habit formation.


Phylogeny determines the role of helminth parasites in intertidal food webs.
1. Parasites affect interactions among species in food webs and should be considered in any analysis of the structure, dynamics or resilience of trophic networks. 2. However, the roles of individual parasite species, such as their importance as connectors within the network, and what factors determine these roles, are yet to be investigated. Here, we test the hypotheses that the species roles of trematode, cestode and nematode parasites in aquatic food webs are influenced by the type of definitive host they use, and also determined by their phylogenetic affiliations. 3. We quantified the network role of 189 helminth species from six highly resolved intertidal food webs. We focused on four measures of centrality (node degree, closeness centrality, betweenness centrality and eigenvalue centrality), which characterize each parasite's position within the web, and on relative connectedness of a parasite species to taxa in its own module vs. other modules of the web (within-module degree and participation coefficient). 4. All six food webs displayed a significant modular structure, that is, they consisted of subsets of species interacting mostly with each other and less with species from other subsets. We demonstrated that the parasites themselves are not generating this modularity, though they contribute to intermodule connectivity. 5. Mixed-effects models revealed only a modest influence of the type of definitive host used (bird or fish) and of the web of origin on the different measures of parasite species roles. In contrast, the taxonomic affiliations of the parasites, included in the models as nested random factors, accounted for 37-93% of the total variance, depending on the measure of species role. 6. Our findings indicate that parasites are important intermodule connectors and thus contribute to web cohesion. We also uncover a very strong phylogenetic signal in parasite species roles, suggesting that the role of any parasite species in a food web, including new invasive species, is to some extent predictable based solely on its taxonomic affiliations.


Apoptosis, Fas and Fas-ligand expression in melanocytic tumors.
Impaired regulation of apoptosis is known to be associated with the development of various forms of cancer. Fas binding to its ligand, Fas ligand (Fas-L), has been shown to trigger apoptosis in various cell types. Fas-L is expressed by melanoma cells and has been suggested to play a role in melanoma escape from immune surveillance. In the present study, we assessed apoptotic activity and examined Fas and Fas-L expression in malignant melanomas, Spitz nevi and ordinary melanocytic nevi. We evaluated apoptotic activity using terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling. Apoptotic activity was found to be minimal in melanomas and moderate in Spitz nevi. In contrast, common nevi demonstrated significant levels of apoptosis in the deep parts of the tumor. Fas was found to be expressed by all Spitz nevi, most melanocytic nevi and approximately half of the malignant melanoma specimens. Fas expression was also significantly more pronounced in Spitz nevus cells as compared with the two other tumors. The anti-Fas-L antibody was found to stain all three melanocytic tumors. Staining was shown to be stronger and more frequent in melanoma cells as compared to the nevus cells. Using the Spearman test, no significant correlation between Fas-L expression in melanoma cells and apoptosis in MM-infiltrating mononuclear cells was found, suggesting that Fas-L expression in melanoma cells may not be instrumental in their ability to escape immune mechanisms of defense. In contrast, increased levels of apoptosis in the deep parts of melanocytic nevi may reflect and possibly contribute to their benign nature.


Supraspinal gene transfer by intrathecal adeno-associated virus serotype 5.
We report the pattern of transgene expression across brain regions after intrathecal delivery of adeno-associated virus serotype 5 (AAV5). Labeling in hindbrain appeared to be primarily neuronal, and was detected in sensory nuclei of medulla, pontine nuclei, and all layers of cerebellar cortex. Expression in midbrain was minimal, and generally limited to isolated neurons and astrocytes in the cerebral peduncles. GFP immunoreactivity (-ir) in thalamus was most prominent in medial geniculate nucleus, and otherwise limited to posterior nuclei of the dorsal and lateral margins. Labeling was also observed in neurons and astrocytes of the hippocampal formation and amygdaloid complex. In the hippocampal formation, GFP-ir was found in neuronal cell bodies of the rostral ventral portion, but was largely restricted to fiber-like staining in the molecular layer of dentate gyrus and stratum lacunosum-moleculare of the rostral dorsal region. GFP-ir was seen in neurons and astroglia throughout caudal cortex, whereas in rostral regions of neocortex it was limited to isolated neurons and non-neuronal cells. Labeling was also present in olfactory bulb. These results demonstrate that intrathecal delivery of AAV5 vector leads to transgene expression in discrete CNS regions throughout the rostro-caudal extent of the neuraxis. A caudal-to-rostral gradient of decreasing GFP-ir was present in choroid plexus and Purkinje cells, suggesting that spread of virus through cerebrospinal fluid plays a role in the resulting transduction pattern. Other factors contributing to the observed expression pattern likely include variations in cell-surface receptors and inter-parenchymal space.


The Femoral Epicondylar Frame to track femoral rotation in optoelectronic gait analysis.
Relative movement of skin markers to underlying bone limits a valid interpretation of axial femorotibial rotation in noninvasive optoelectronic gait analysis. A distal femoral clamp is a practical solution for thigh marker placement, however, existing devices are still susceptible to measurement errors at increased angles of knee flexion. We developed the Femoral Epicondylar Frame (FEF), which should result in less femoral rotational measurement error due to its anatomic fitting and controlled pressure adjustment. Seven subjects with a total knee replacement in situ, mean age 71 years, mean body mass index 28, were equipped with the frame mounted with a set of tantalum markers. Fluoroscopic data was collected during a step-up motion. A three-dimensional model fitting technique was used to compare the in vivo position and orientation of the frame and the femoral prosthesis component of the prosthesis. The frame rotational measurement error appeared to be linearly dependent on the knee flexion angle. When considering knee flexion angles lower than 40° of flexion, the highest measurement error was 3.3° on average, with an absolute extreme of 6.2°. It is concluded that the accuracy of the FEF is sufficient to evaluate axial knee rotation with optoelectronic gait analysis at group level in clinical studies.


Cultured rat mesothelial cells generate hydrogen peroxide: a new player in peritoneal defense?
This study was designed to examine whether rat peritoneal mesothelial cells in culture could generate hydrogen peroxide in different experimental conditions. Mesothelial cells, incubated in M-199, spontaneously released hydrogen peroxide. This process was significantly increased by addition of phorbol myristate acetate, as well as of superoxide dismutase to the medium, whereas it was substantially inhibited by catalase. Exposure of mesothelial cells to modified M-199 medium with 1.5% glucose concentration-lactated peritoneal dialysis solution did not seem to interfere either with the spontaneous release of hydrogen peroxide, or with that induced by phorbol myristate acetate. Furthermore, exposure of mesothelial cells to the glucose (4.25%) peritoneal dialysis solution in Medium M-199, was coincident with increased hydrogen peroxide generation, which was significantly higher than the spontaneous release, and not far from that observed with phorbol myristate acetate and superoxide dismutase. So far, it can be inferred from this evidence that peritoneal mesothelial cells in culture are not only endowed with the capability of producing hydrogen peroxide, but they can also be activated to do so in a way comparable to that observed in neutrophils and macrophages. This attribute is one more indication that mesothelial cells play a relevant role in the peritoneal mechanism of defense against infection. On the other hand, continuous exposure of mesothelial cells to glucose-enriched fluids, as occurs in clinical continuous ambulatory peritoneal dialysis, may well also be at the origin of a process of continuous injury, resulting from an increased hydrogen peroxide generation.


Risk Factors for Rotator Cuff Disease: An Experimental Study on Intact Human Subscapularis Tendons.
Although several studies revealed a multifactorial pathogenesis of degenerative rotator cuff disorders, the impact and interaction of extrinsic variables is still poorly understood. Thus, this study aimed at uncovering the effect of patient- and pathology-specific risk factors that may contribute to degeneration of the rotator cuff tendons. Between 2015 and 2018, 54 patients who underwent arthroscopic shoulder surgery at three specialized shoulder clinics were prospectively included. Using tendon samples harvested from the macroscopically intact subscapularis (SSC) tendon, targeted messenger RNA expression profile analysis was performed in the first cohort (n = 38). Furthermore, histological analyses were conducted on tendon tissue samples obtained from a second cohort (n = 16). Overall, both study cohorts were comparable concerning patient demographics. Results were then analyzed with respect to specific extrinsic factors, such as patient age, body mass index, current as well as previous professions and sport activities, smoking habit, and systemic metabolic diseases. While patient age, sports-activity level, and preexisting rotator cuff lesions were considered to contribute most strongly to tendinopathogenesis, no further coherences were found. With regards to gene expression analysis, change in expression correlated most strongly with patient age and severity of the rotator cuff pathology. Further, chronic disorders increased overall gene expression variation. Taken together, our study provides further evidence that tendon degeneration is the consequence of a multifactorial process and pathological changes of the supraspinatus tendon affect the quality of SSC tendon and most likely vice versa. Therefore, the rotator cuff tendons need to be considered as a unit when managing rotator cuff pathologies. © 2019 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society J Orthop Res 38:182-191, 2020.


HS3ST1 genotype regulates antithrombin's inflammomodulatory tone and associates with atherosclerosis.
The HS3ST1 gene controls endothelial cell production of HSAT+ - a form of heparan sulfate containing a specific pentasaccharide motif that binds the anticoagulant protein antithrombin (AT). HSAT+ has long been thought to act as an endogenous anticoagulant; however, coagulation was normal in Hs3st1-/- mice that have greatly reduced HSAT+ (HajMohammadi et al., 2003). This finding indicates that HSAT+ is not essential for AT's anticoagulant activity. To determine if HSAT+ is involved in AT's poorly understood inflammomodulatory activities, Hs3st1-/- and Hs3st1+/+ mice were subjected to a model of acute septic shock. Compared with Hs3st1+/+ mice, Hs3st1-/- mice were more susceptible to LPS-induced death due to an increased sensitivity to TNF. For Hs3st1+/+ mice, AT treatment reduced LPS-lethality, reduced leukocyte firm adhesion to endothelial cells, and dilated isolated coronary arterioles. Conversely, for Hs3st1-/- mice, AT induced the opposite effects. Thus, in the context of acute inflammation, HSAT+ selectively mediates AT's anti-inflammatory activity; in the absence of HSAT+, AT's pro-inflammatory effects predominate. To explore if the anti-inflammatory action of HSAT+ also protects against a chronic vascular-inflammatory disease, atherosclerosis, we conducted a human candidate-gene association study on >2000 coronary catheterization patients. Bioinformatic analysis of the HS3ST1 gene identified an intronic SNP, rs16881446, in a putative transcriptional regulatory region. The rs16881446G/G genotype independently associated with the severity of coronary artery disease and atherosclerotic cardiovascular events. In primary endothelial cells, the rs16881446G allele associated with reduced HS3ST1 expression. Together with the mouse data, this leads us to conclude that the HS3ST1 gene is required for AT's anti-inflammatory activity that appears to protect against acute and chronic inflammatory disorders.


Anti-arthritic activity of root bark of Oroxylum indicum (L.) vent against adjuvant-induced arthritis.
Oroxylum indicum (Bignoniaceae) also known as Sonapatha is an indigenous medicinal plant widely used in Ayurvedic medicine for over thousands of years. It is an active ingredient of well-known Ayurvedic formulations such as Chyawanprash and Dasamula. Root bark of this plant has tonic and astringent properties and it is also used in rheumatism. The present investigation was carried out to evaluate the anti-arthritic activity of different extracts of root bark of Oroxylum indicum against adjuvant - induced arthritis in rats. Male Wistar rats were used in this study. Arthritis was induced by injecting 0.1 ml Freund's complete adjuvant intra-dermally into the left hind paw of the rats. The paw volume, hematological, biochemical, radiographic and histopathological aspects were evaluated. The relative percentage inhibition potential of paw volume in rats treated with various extracts of Oroxylum indicum was found to be ethyl acetate extract (67.69%) >chloroform extract (64.61%) >n-butanol extract (58.46%) respectively. The hematological parameters like RBC count, hemoglobin content showed significant increase while there was a significant decrease in total WBC count and ESR in all the groups of animals pretreated with root bark extracts. The biochemical parameters such as catalase, glutathione contents showed a significant increase while the lipid peroxide and Cathepsin-D content decreased significantly only in case of ethyl acetate pretreated rats when compared to others. The present study suggests that the chloroform, ethyl acetate and n-butanol extracts of root bark of Oroxylum indicum exhibit anti-arthritic activity. The order of activity of extracts was found to be ethyl acetate >chloroform >n-butanol respectively.


Progesterone administration in vivo stimulates release of luteinizing hormone-releasing hormone in vitro.
The release of luteinizing hormone-releasing hormone (LHRH) from tissue from the mediobasal hypothalamic-anterior hypothalamic-preoptic area of prepuberal female rats was measured in a perfusion system. Measurements were also made of the concentrations of LHRH in these tissue fragments and of luteinizing hormone in serum obtained when the rats were killed. Four groups of immature rats were studied: intact, ovariectomized, ovariectomized and implanted with estradiol-containing capsules, and ovariectomized rats primed with estradiol and injected with progesterone. The release of LHRH from the tissue of ovariectomized animals was significantly less than that of intact females and was not modified when the ovariectomized rats received estradiol. However, there was a four- to fivefold increase in LHRH release from tissue of ovariectomized rats primed with estradiol when they were killed 6 hours after they received an injection of progesterone. The concentrations of LHRH in tissue and of luteinizing hormone in serum varied among groups and with the time of day that the animals were killed. The interactions among luteinizing hormone, gonadal steroids, and the photoperiod seem to set the appropriate conditions for neural processes triggering a complete and normal release of luteinizing hormone.


Requirement of the galU gene for polysaccharide production by and pathogenicity and growth In Planta of Xanthomonas citri subsp. citri.
Xanthomonas citri subsp. citri is the causal agent of citrus canker, which has a significant impact on citrus production. In this study, we characterized the galU gene of X. citri subsp. citri. Two galU mutants (F6 and D12) were identified in an X. citri subsp. citri EZ-Tn5 <R6Kgammaori/KAN-2> Tnp transposon library. Rescue cloning, sequence analysis, and Southern blot analysis indicated that both of these mutants had a single copy of the EZ-Tn5 transposon inserted in galU in the chromosome. Further study showed that galU was required for biosynthesis of extracellular polysaccharides (EPS; xanthan gum) and capsular polysaccharide (CPS) and biofilm formation. Mutation of galU resulted in a loss of pathogenicity for grapefruit. The loss of pathogenicity of a galU mutant resulted from its inability to grow in planta rather than from the effect on virulence genes. Quantitative reverse transcription-PCR assays indicated that mutation of galU did not impair the expression of key virulence genes, such as pthA of X. citri subsp. citri. Although D12 had a growth rate similar to that of the wild-type strain in nutrient broth, no D12 population became established in the intercellular spaces of citrus leaves. Coinoculation of a galU mutant with the wild-type strain did not promote growth of the galU mutant in planta. Defects in EPS and CPS production, pathogenicity, and growth in planta of the galU mutant were complemented to the wild-type level using plasmid pCGU2.1 containing an intact galU gene. These data indicate that the galU gene contributes to X. citri subsp. citri growth in intercellular spaces and is involved in EPS and CPS synthesis and biofilm formation.


Dynamics of venous-arterial testosterone transfer in the pampiniform plexus of the rat.
The dynamics of venous-arterial testosterone transfer in the pampiniform plexus of the rat have been studied using [3-H] testosterone in controlled perfusion in the pampiniform plexus isolated from its testicle in vivo. The rate of transfer of testosterone increased in direct proportion to the testosterone concentration in spermatic vein blood over the range 0-100 ng/ml. When the venous-arterial concentration gradient was reversed by infusing [14-C] testosterone into the spermatic artery proximal to the pampiniform plexus, the label was transferred from the artery to the adjacent spermatic vein. Transfer of [3-H] methoxy-inulin infused concomitantly with the [14-C] testosterone was relatively insignificant in either direction. The testosterone transfer rate generally increased with increasing blood flow over the range 0.01-0.36 ml/min. However, transfer rate became less dependent on blood flow at the high end of the range. A comparison of transfer rates from whole blood and dextran (6% in saline) each containing 24-27 ng [1,2-3-H] testosterone/ml and flowing at 0.36 ml/min for one hour resulted in a maximum of 6.1% transfer from blood and 46% transfer from dextran. Transfer from blood reached plateau levels in less than 10 min, whereas transfers from dextran peaked between 30 and 40 min. At lower rates testosterone transfer from dextran reached equilibration levels, whereas transfer from blood rarely exceeded 5% of spermatic venous levels. We concluded that venous-arterial steroid transfer in the pampiniform plexus behaves like a passive countercurrent diffusion system that is concentration limited, depending principally on the concentration gradient of diffusible steroid between the closely juxtaposed spermatic vein and artery.


Reduced norepinephrine turnover in brown adipose tissue of ob/ob mice.
Obese (ob/ob) mice have a lower thermogenic capacity than lean mice. The possible role of brown adipose tissue (BAT) in this defect was investigated. Lean and obese mice were exposed to 33 (thermoneutral), 25, or 14 degrees C for up to 3 wk. BAT cytochrome oxidase activity and numbers of Na+-K+-ATPase enzyme units, enzymes involved in thermogenesis, were similar at 33 or 25 degrees C. Chronic exposure to 14 degrees C increased these enzymes 34 and 62%, respectively, in lean mice and nearly 150% in obese mice. Sympathetic nervous system activity, which stimulates thermogenesis in BAT, was evaluated by measuring norepinephrine (NE) turnover. At 25 degrees C, NE turnover rate in BAT of obese mice was only 40% as rapid as in BAT of lean mice. Chronic exposure to 33 degrees C depressed NE turnover in BAT of lean mice, but not in obese mice, whereas exposure to 14 degrees C accelerated NE turnover in both lean and obese mice. Lower sympathetic nervous system activity in BAT of obese mice at 25 degrees C is likely a major factor in their reduced nonshivering thermogenesis and resultant high efficiency of energy storage.


The neutralization of interleukin-5 as a therapeutic concept in allergic inflammation.
Interleukin-5 (IL-5) is an eosinophil differentiation factor. Therefore, increased levels of IL-5 in the bone marrow are associated with increased eosinophil numbers in blood. In addition, IL-5 increases the sensitivity of eosinophils towards other stimuli and delays their cell death. In contrast to other cytokines, IL-5 acts on a limited number of cells only. In fact, high-affinity IL-5 receptors are exclusively expressed by eosinophils and basophils, but no other human cells. Therefore, neutralization of IL-5 appears to be an obvious approach to treat eosinophilic disorders, since no major side effects due to effects on other cells are expected. Results from animal experiments suggested that anti-IL-5 antibodies may have anti-asthmatic activities. In this article, I summarize our current knowledge regarding anti-IL-5 therapy and speculate on the potential use of these drugs in the future.


Cryopreservation of autologous fat grafts harvested with the Coleman technique.
The viability of fat grafts harvested with an established technique after cryopreservation remains unknown. This study was conducted in vitro to evaluate the viability of autologous fat grafts harvested with the Coleman technique and subsequently preserved with our preferred cryopreservation method. Eight adult females were enrolled in this study. In each patient, 10 mL of fat grafts were harvested with the Coleman technique by a single surgeon from the lower abdomen. In group 1, 5 mL of fresh fat grafts were mixed with cryoprotective agents and underwent cryopreservation with controlled slow cooling and fast rewarming. In group 2, 5 mL of fresh fat grafts without cryopreservation from the same patient served as a control. The fat graft samples from both groups were evaluated with trypan blue vital staining, glycerol-3-phophatase dehydrogenase assay, and routine histology. Viable adipocyte counts were found similar in both group 1 and group 2 (3.46 +/- 0.91 vs. 4.12 +/- 1.11 x 10/mL, P = 0.22). However, glycerol-3-phophatase dehydrogenase activity was significantly lower in group 1 compared with group 2 (0.47 +/- 0.09 vs. 0.66 +/- 0.09 u/mL, P < 0.001). Histologically, the normal structure of fragmented fatty tissues was found primarily in both groups. Our results indicate that autologous fat grafts harvested with the Coleman technique and preserved with our preferred cryopreservation method have a normal histology with near the same number of viable adipocytes as compared with the fresh fat grafts. However, those cryopreserved fat grafts appear to have a less optimal level of adipocyte specific enzyme activity compared with the fresh ones and thus may not survive well after they are transplanted without being optimized.


Relevance of religion and spirituality in German patients with chronic diseases.
Many American patients depend on religion to cope, but less is known about the spiritual/religious (SpR) characteristics of medical patients in Europe, a more secular environment. We examined self-categorizations of SpR (spiritual, religious, both, neither), patients' search for meaningful support, trust in higher source, positive interpretation of disease, and support in relations of life through SpR, as measured with the SpREUK questionnaire, in German medical patients. We analyzed data on 710 West-German patients with a mean age of 54. Forty-two percent had chronic pain diseases, 25% cancer, 10% multiple sclerosis, 21% other chronic diseases, and 3% acute diseases. The general interest in search for meaningful support was moderate. Trust in a higher source and support in life through SpR were rated higher, while almost all patients had a positive interpretation of their diseases, i.e, hint to change life. The interest in SpR issues was highest in cancer patients and lowest in patients with multiple sclerosis. Univariate analyses confirmed that the SpR self-categorization was the strongest predictor of all four factors, while trust in a higher source was also affected by religious affiliation and age. Positive interpretations of disease correlated well with search for meaningful support. Patients with chronic diseases differ with respect to their SpR self-categorizations and may thus utilize different aspects of SpR. Cancer patients, in particular, often depend on their trust in a higher power and in conventional religious activities to help them to cope with their illness.


Dawestrema cycloancistrium (Monogenea) from the head pores of arapaimas.
Arapaima gigas is one of the main cultured fish species in South America, and monogenean parasites of this species cause large economic losses to fish farmers. During surveys of the parasites of cultured arapaimas from Mexiana Island in the Amazon River Delta, Rio Branco, in northwestern Brazilian Amazonia, and Yurimaguas, Peru, the monogenean Dawestrema cycloancistrium was found in the gills of A. gigas as well as in previously unreported sites, i.e. the head pores and chambers. The aim of this study was to investigate the transmission route of this parasite and its geographical distribution as well as to describe its morphology as observed by light and confocal imaging. Phalloidin labeling confirmed the presence of 2 prostatic reservoirs and showed muscular branches of fibers supporting haptoral sclerites. In arapaimas, the head connects to the gill chambers via 2 perforated scales located at the dorsolateral sides of the distal part of the head. The scales connect to thin channels and chambers situated in the proximal part of the head. These chambers are filled with cephalic mucus, which flows out to the environment through terminal pores. Adults and egg masses of monogeneans were found on the gills and inside the head pores and cavities of fish along with cephalic mucus. This indicates a specialized method of parasite transmission from adult fish to fingerlings during parental care (holding offspring in the mouth) or via head secretions, providing evidence of a new adapted mechanism of dispersion.


Starting a pediatric contrast ultrasound service: made simple!
The addition of contrast US to an existing pediatric US service requires several preparatory steps. This overview provides a guide to simplify the process. Initially, it is important to communicate to all stakeholders the justifications for pediatric contrast US, including (1) its comparable or better diagnostic results relative to other modalities; (2) its reduction in procedural sedation or anesthesia by avoiding MRI or CT; (3) its reduction or elimination of radiation exposure by not having to perform fluoroscopy or CT; (4) the higher safety profile of US contrast agents (UCA) compared to other contrast agents; (5) the improved exam comfort and ease inherent to US, leading to better patient and family experience, including bedside US exams for children who cannot be transported; (6) the need for another diagnostic option in light of increasing demand by parents and providers; and (7) its status as an approved and reimbursable exam. It is necessary to have an UCA incorporated into the pharmacy formulary noting that only SonoVue/Lumason is currently approved for pediatric use. In the United States this UCA is approved for intravenous administration for cardiac and liver imaging and for vesicoureteric reflux detection with intravesical application. In Europe and China it is only approved for the intravesical use in children. All other applications are off-label. The US scanner needs to be equipped with contrast-specific software. The UCA has to be prepared just before the exam and it is important to strictly follow the steps as outlined in the packaging inserts in order to prevent premature destruction of the microbubbles. The initial training in contrast US is best focused on the frontline staff actually performing the US studies; these might be sonographers, pediatric or interventional radiologists, or trainees. It is important from the outset to educate the referring physicians about contrast US. It is helpful to participate in existing contrast US courses, particularly those with hands-on components.


Equilibrium Solvation, Electron-Transfer Reactions, and Stokes-Shift Dynamics in Ionic Liquids.
A microscopic theory of solvent response by room-temperature ionic liquids is formulated based on the dynamic longitudinal susceptibility of liquid's charge density. The susceptibility function combines the structural information in terms of reciprocal-space structure factors with the memory function responsible for solvation dynamics. The charge-density structure factors and corresponding intermediate scattering functions are analyzed here by molecular dynamics simulations. They show the existence of two drastically different time scales of charge-density fluctuations. Faster, stretched-exponential dynamics are consistent with dielectric measurements. It contributes to the Stokes-shift dynamics of coumarin-153 optical dye calculated with the new theory and compared to experimental reports. The second, much slower and exponential, relaxation shows the phenomenology of de Gennes narrowing: the relaxation time passes through a strong maximum at the wave vector representing the first peak of the structure factor. This peak, which is particularly sharp for the charge density, contributes significantly to the equilibrium free energy of solvation, thus invalidating dielectric theories of solvation for ionic liquids. Dynamics of charge density fluctuations at the length scale consistent with the sharp peak require long observation times. Electron-transfer reactions occurring on faster time-scales are not affected by these slow dynamics. Nonergodic reorganization energy of electron transfer, accounting for the observation window established by the reaction time, drops sharply when the reaction rate crosses the main peak in the Stokes-shift loss spectrum. The dependence of the reorganization energy on the reaction rate strongly affects the energy-gap law of electron transfer, with a tendency for a shallow or entirely disappearing inverted region.


EFFECT OF THE APOE ε4 ALLELE AND COMBAT EXPOSURE ON PTSD AMONG IRAQ/AFGHANISTAN-ERA VETERANS.
The apolipoprotein E (APOE) ε4 allele has been implicated in a range of neuropsychiatric conditions. The present research examined if the ε4 allele of the APOE gene moderated the effect of combat exposure on posttraumatic stress disorder (PTSD) among Iraq/Afghanistan-era veterans. Participants included 765 non-Hispanic White (NHW) and 859 non-Hispanic Black (NHB) Iraq/Afghanistan-era veterans. A structured interview established psychiatric diagnoses. Combat exposure and PTSD symptom severity were assessed via self-report. The most common lifetime diagnoses were depression (39.2%), PTSD (38.4%), and alcohol dependence (24.38%). After correcting for multiple comparisons, no significant effects were observed on any of the outcomes among the NHW sample; however, within the NHB sample, significant gene × environment (G × E) interactions were observed for lifetime PTSD (P = .0029) and PTSD symptom severity (P = .0009). In each case, the APOE ε4 allele had no effect on the outcomes when combat exposure was low; however, when combat exposure was high, an additive effect was observed such that ε4 homozygotes exposed to high levels of combat reported the highest rates of PTSD (92%) and the worst symptom severity scores on the Davidson Trauma Scale (M = 79.5). Although preliminary, these findings suggest that the APOE ε4 allele, in conjunction with exposure to high levels of combat exposure, may increase veterans' risk for developing PTSD.


How Zinc-Binding Systems, Expressed by Human Pathogens, Acquire Zinc from the Colonized Host Environment: A Critical Review on Zincophores.
Some transition metals, like manganese, iron, cobalt, nickel, copper and zinc, required for the biosynthesis of metalloenzymes and metalloproteins, are essential micronutrients for the growth and development of pathogenic microorganisms. Among the defenses put in place by the host organism, the so-called "nutritional immunity" consists of reducing the availability of micronutrients and thus "starving" the pathogen. In the case of metals, microorganisms can fight the nutritional immunity in different ways, i.e. by directly recruiting the metal ion or capturing an extracellular metalloprotein or also through the synthesis of specific metallophores which allow importing the metal in the form of a chelate complex. The best known and most studied metallophores are those directed to iron (siderophores), but analogous chelators are also expressed by microorganisms to capture other metals, such as zinc. An efficient zinc recruitment can also be achieved by means of specialized zinc-binding proteins. A deep knowledge of the properties, structure and action mechanisms of extracytoplasmic zinc chelators can be a powerful tool to find out new therapeutic strategies against the antibiotic and/or antifungal resistance. This review aims to collect the knowledge concerning zincophores (small molecules and proteins in charge of zinc acquisition) expressed by bacterial or fungal microorganisms that are pathogenic for the human body.