TL-61 versus Rohadur orthoses in heel spur syndrome.
The authors present the subjective responses of 40 patients with heel spur syndrome or plantar fascitis to orthotic treatment. Twenty patients had Rohadur orthoses and 20 patients had TL-61 orthoses. These data show no difference in the response to or problems created by either TL-61 or Rohadur orthoses. The authors recommend TL-61 as one alternative to Rohadur, now that that latter is unavailable.


Endovascular treatment of acute gastrointestinal bleeding from a large splenic artery pseudoaneurysm: case report and literature review.
Pseudoaneurysm of the splenic artery is a rare entity, with little more than 150 cases described in the literature. Pancreatitis is the most common etiology, followed by trauma. In contrast with true aneurysms, pseudoaneurysms are frequently symptomatic, with a 47% risk of rupture and 90% mortality if left untreated. We describe the case of a 48-year-old female patient who suffered a gastrointestinal hemorrhage associated with acute-on-chronic pancreatitis. During workup, endoscopy revealed signs of recent bleeding and magnetic resonance angiography of the abdomen showed a large pseudoaneurysm of the splenic artery. The patient underwent endovascular treatment with microcoil embolization and no further bleeding episodes occurred. Endovascular treatment is now an effective option with low morbidity and mortality and success rates in the range of 79-100%, making it a viable technique for patients with active abdominal inflammation. We conducted a review of endovascular techniques and embolization agents used to treat this pathology.


Optical pupillometry in traumatic brain injury: neurological pupil index and its relationship with intracranial pressure through significant event analysis.
Primary Objective: Treatment paradigms for traumatic brain injury (TBI) rely on invasive monitoring of intracranial pressure (ICP) for planning intervention. Optical pupillometry is a non-invasive, objective monitoring method, measuring parameters of pupillary response and displaying a scalar value - a neurological pupil index (NPi). An impaired response on NPi has been tentatively correlated with ICP, through analysis of mean/peak NPi and ICP readings. We sought to evaluate this relationship more closely. Research Design: Prospective observational. Methods and Procedures: We obtained hourly pupillometry readings, alongside ICP values, from 40 patients with TBI requiring invasive ICP monitoring. Significant events were identified for analysis based on the significant aberration of ICP or NPi. Main Outcomes and Results: On average, individuals experienced a few significant events. There was a weak relationship between ICP events and a preceding NPi event. The results show that there is a weak but statistically insignificant relationship between NPi and ICP, where reduced pupil reactivity may indicate a raised ICP. The strength of this trend appears to diminish post-decompressive surgery. Conclusions: Whilst pupillometry may not be a reliable surrogate marker for ICP, NPi may still prove to be a useful tool in a multimodal prognostic assessment of the patient with acute brain injury.


N- and O-glycosylation analysis of etanercept using liquid chromatography and quadrupole time-of-flight mass spectrometry equipped with electron-transfer dissociation functionality.
Etanercept is a highly glycosylated therapeutic Fc-fusion protein that contains multiple N- and O-glycosylation sites. An in-depth characterization of the glycosylation of etanercept was carried out using liquid chromatography/mass spectrometry (LC/MS) methods in a systematic approach in which we analyzed the N- and O-linked glycans and located the occupied O-glycosylation sites. Etanercept was first treated with peptide N-glycosidase F to release the N-glycans. The N-glycan pool was labeled with a 2-aminobenzamide (2-AB) fluorescence tag and separated using ultraperformance liquid chromatography-hydrophilic interaction liquid chromatography (UPLC-HILIC). Preliminary structures were assigned using Glycobase. These assignments, which included monosaccharide sequence and linkage information, were confirmed by exoglycosidase array digestions of aliquots of the N-glycan pool. The removal of the N-glycans from etanercept facilitated the selective characterization of O-glycopeptides and enabled the O-glycans to be identified. These were predominantly of the core 1 subtype (HexHexNAc O-structure) attached to Ser/Thr residues. α2→3,6,8,9 sialidase was used to remove the sialic acid residues on the O-glycans allowing the use of an automated LC/MS(E) protocol to identify the O-glycopeptides. Electron-transfer dissociation (ETD) was then used to pinpoint the 12 occupied O-glycosylation sites. The determination of N- and O-glycans and O-glycosylation sites in etanercept provides a basis for future studies addressing the biological importance of specific protein glycosylations in the production of safe and efficacious biotherapeutics.


Understanding the link between childhood maltreatment and violent delinquency: what do schools have to add?
Child maltreatment constitutes significant risk for adolescent delinquency. Although an ecological model has been proposed to explain this relationship, most studies focus on individual risk factors. Prospective data from 1,788 students attending 23 schools were used to examine the additive influence of childhood maltreatment, individual-level risk factors, and school-level variables assessed at the beginning of Grade 9 on delinquency 4 to 6 months later. Individual-level results indicated that being male, experiencing childhood maltreatment, and poor parental nurturing were predictors of violent delinquency. School climate also played a significant role: Given the same individual risk profile, a student attending a school that was perceived by students as safe was less likely to engage in violent delinquency than was a student attending a school perceived to be unsafe. Moreover, the impact of childhood maltreatment on risk for engaging in violent delinquency was somewhat mitigated by schools' participation in a comprehensive violence prevention program.


Effortless Extraction of Structural and Orientational Information from 13C-1H Dipolar Couplings for Thiophene Mesogens.
Five molecular mesogens containing phenyl rings and thiophene are subjected to a detailed 13C NMR investigation. The first mesogen contains only phenyl rings, while the other four have thiophene with substitution at position 2 or 3. Two of these also have a spacer inserted between the thiophene and the rest of the core unit. The mesophase properties evaluated by complementary techniques reveal an enantiotropic nematic phase for all the cases and smectic C as well as Crystal J for a few mesogens. In addition to solution 13C NMR, the samples were studied using 1D and 2D solid-state 13C NMR experiments in the liquid crystalline phase. The chemical shifts and 13C-1H dipolar couplings obtained in the mesophase provided cutting-edge information about the molecular structure and orientation of the thiophene mesogens. Accordingly, dramatic differences in these parameters are noted for the mesogens, and consequently, the identification of 2- and 3-substituted thiophene mesogens is accomplished by a simple visual examination of the 2D spectra. Furthermore, for mesogens with a spacer between thiophene and the rest of the core, 13C chemical shifts and 13C-1H dipolar couplings showed remarkable variation, which was directly reflected in the order parameters. For instance, the order parameter (Szz) of thiophene in 2- and 3-substituted mesogens in which the spacer is absent is ∼0.63 whereas for those with spacer, it is reduced to ∼0.14-0.18. In comparison, the mesogen in which the core unit is made up of phenyl rings alone that is used to benchmark the characteristics of thiophene ordering showed an order parameter of ∼0.85. The study unambiguously demonstrates the supremacy of 13C NMR in extracting the structural and orientational information on mesogens in which thiophene is a constituent of the core unit.


Contrast-enhanced MR angiography of the hand.
Contrast material-enhanced magnetic resonance (MR) angiography of the hand noninvasively provides information comparable to that provided by conventional angiography. It is a quick and easy examination that takes less than 5 minutes to perform and produces high-quality images with use of a dedicated surface coil that provides a high signal-to-noise ratio, allowing small pixel size and high spatial resolution. Contrast-enhanced MR angiography requires intravenous injection of gadopentetate dimeglumine and acquisition of a volumetric slab of image data from the hand. This information is then projected with a maximum-intensity-projection algorithm. The technique is generally robust with reproducible findings. Image interpretation requires an understanding of (a) the normal vascular anatomy and anatomic variants of the hand and (b) common vascular diseases. MR angiography of the hand is commonly used to create an arterial "road map" prior to surgery, manage traumatic transection, and identify emboli. Vascular malformations are readily identified and connective tissue disorders including vasculitis are well demonstrated with this technique, which can also be used to assess bone viability following trauma to the carpus or to evaluate the viability of vascularized bone. Common artifacts may be secondary to contracture deformities or "wraparound" effect. However, most potential pitfalls can be avoided by being vigilant.


"Falling Through the Cracks": A Retrospective Exploration of the Barriers to Help-Seeking Among Men Convicted of Sexual Crimes.
The prevalence and impact of sexual abuse is of global concern, and the alarming rates of victimization have inspired a focus on its prevention. Whilst research has begun to explore the experiences of non-offending individuals to inform prevention initiatives, there is limited exploration of those who have struggled with their sexual interests and go on to commit sexual crime. Arguably these individuals hold key information about gaps in service provision, which may inform approaches to crime prevention. This study aimed to provide a phenomenological exploration of the pre-offense experiences of convicted individuals' beliefs about help-seeking, their desires for support, and any barriers that might have prevented them from coming forward for help. Semi-structured interviews were conducted with 14 individuals convicted of sexual offenses (n = 13 against children; n = 1 sexually motivated violence), and interpretative phenomenological analysis elicited three superordinate themes: Desperation, Barriers to Help-seeking and A Way Forward. The findings shed light on the distressing experience of living with sexual interests that are so openly rejected by society and the many ways participants attempted to cope with this, including multiple failed attempts to seek help. Implications and limitations are discussed.


Adoptive transfer of dendritic cells from allergic mice induces specific immunoglobulin E antibody in naïve recipients in absence of antigen challenge without altering the T helper 1/T helper 2 balance.
Dendritic cells (DCs) are important in the regulation of immune responses and it has been proposed that these cells play an important role in asthma; however, their role in food allergy is still largely unknown. Our aim was to study specific immunoglobulin E (IgE) and immunoglobulin G (IgG) responses in naïve recipients following adoptive transfer of myeloid DCs from allergic and control mice. The phenotypic features and lymphokine production of DCs were also investigated. CD11c+/hi B220- DCs isolated from spleen and Peyer's patches (PP) of cow's milk (CM) allergic and control mice were transferred intravenously (i.v.) into naïve syngeneic recipients, and IgE- and IgG-specific responses were evaluated. Experiments were also carried out to determine the levels of interferon-gamma (IFN-gamma) and interleukin (IL)-4 produced by splenocytes from naïve recipients following the adoptive transfer, and CD40 ligand (CD40L)-mediated IL-10 production by DCs from allergic and control mice. DCs isolated from spleen and PP of allergic mice, but not control groups, induced CM-specific IgG and IgE antibody production in naïve recipients in the absence of previous immunization, but did not modify the T helper 1 (Th1) and T helper 2 (Th2) balance. Furthermore, although no difference was observed in the expression of canonical DC surface markers, PP DCs from allergic mice produced less IL-10 than DCs from controls. We interpret these data as showing that DCs play a pivotal role in allergen-specific IgE responses and that a Th2-skewed response may not be involved in the early phase of allergic responses. The identification of the mechanisms underlying these events may help to design novel strategies of therapeutic intervention in food allergy.


Coffee consumption in aged mice increases energy production and decreases hepatic mTOR levels.
Coffee, one of the world's most consumed beverages, has many benefits. Some studies have reported the effects of coffee on aging. The aim of this study was to investigate the locomotor activity, energy metabolism, and lipid metabolism of aged (20-mo-old) mice given coffee. Aged C57 BL/6 NCr mice were divided into three groups: controls that were not given coffee (n = 9), a group that received 0.1% caffeinated coffee (n = 9), and a group that received 0.1% decaffeinated coffee (n = 9). This regimen continued for 17 wk until mice reached the age of 24 mo. Regular and decaffeinated coffee consumption decreased plasma-free fatty acid levels, increased hepatic adenosine triphosphate content, and decreased total mammalian target of rapamycin (mTOR) and phosphorylated mTOR (p-mTOR) protein content in the liver. However, no differences were found in the protein or activity levels of Akt, adenosine monophosphate-activated protein kinase (AMPK), p70 S6 kinase, or sterol regulatory element-binding protein 1, proteins that are upstream or downstream of the mTOR complex 1 (mTORC1)-related pathways. Regular coffee consumption increased food and water intake, locomotor activity, the volume of carbon dioxide production, and the respiration exchange ratio. Regular and decaffeinated coffee consumption decreased hepatic total mTOR and p-mTOR levels independently of Akt and AMPK pathways in aged mice. Because decreased mTORC1 activity is known to have antiaging effects, coffee consumption during old age may retard aging. Moreover, coffee consumption by the aged population had a positive effect on behavioral energy and lipid metabolism.


Recombination between IS5 elements: requirement for homology and recombination functions.
Intermolecular recombination between two IS5 elements was measured, using bacteriophage lambda recombination vectors, and was compared to recombination between two copies of an SV40 segment cloned into the same vectors. Experiments were conducted in the presence and in the absence of RecA and Red functions, and with the recombining inserts in the same or in reversed orientation. Under all conditions, IS5 elements recombined in a manner similar to the SV40 inserts, indicating that IS-encoded functions did not confer measurable additional intermolecular recombination ability to IS5 in E. coli K-12. Bacteriophages containing reversed IS5 inserts, for which the 16 base pair (bp) termini are identical in 15 positions and which display 12 bp of uninterrupted homology, recombined at approximately the same low frequency under Rec+ and Rec- conditions, indicating that these short homologies were not good substrates for the Rec system. Bacteriophages having reversed inserts recombined better under Red+ than under Red- conditions, but the crossovers were located in nonhomologous regions flanking the element termini. This suggests that 12-bp homologies are not good substrates for the Red system.


Cytochrome P450s from Cynara cardunculus L. CYP71AV9 and CYP71BL5, catalyze distinct hydroxylations in the sesquiterpene lactone biosynthetic pathway.
Cynara cardunculus (Asteraceae) is a cross pollinated perennial crop which includes the two cultivated taxa globe artichoke and cultivated cardoon. The leaves of these plants contain high concentrations of sesquiterpene lactones (STLs) among which cynaropicrin is the most represented, and has recently attracted attention because of its therapeutic potential as anti-tumor and anti-photoaging agent. Costunolide is considered the common precursor of the STLs and three enzymes are involved in its biosynthetic pathway: i.e. the germacrene A synthase (GAS), the germacrene A oxidase (GAO) and the costunolide synthase (COS). Here we report on the isolation of two P450 genes, (i.e. CYP71AV9 and CYP71BL5), in a set of ∼19,000 C. cardunculus unigenes, and their functional characterization in yeast and in planta. The metabolite analyses revealed that the co-expression of CYP71AV9 together with GAS resulted in the biosynthesis of germacra-1(10),4,11(13)-trien-12-oic acid in yeast. The co-expression of CYP71BL5 and CYP71AV9 with GAS led to biosynthesis of the free costunolide in yeast and costunolide conjugates in Nicotiana benthamiana, demonstrating their involvement in STL biosynthesis as GAO and COS enzymes. The substrate specificity of CYP71AV9 was investigated by testing its ability to convert amorpha-4,11-diene, (+)-germacrene D and cascarilladiene to their oxidized products when co-expressed in yeast with the corresponding terpene synthases.


Spatiotemporal dynamics of a passively mode-locked Nd:GdVO(4) laser.
By examining beam patterns, temporal pulse forms, and radio-frequency spectra as functions of resonator configuration and pump power, we found that a passively mode-locked Nd:GdVO4 laser exhibited four main regimes of operation that were single-transverse-mode Q-switched mode locking (QSML), single-transverse-mode continuous-wave mode locking (CWML), multiple-transverse-modes QSML, and multiple-transverse-modes CWML. The effect of multiple transverse modes on CWML was giving rise to amplitude instability in the pulse train. In the regime of multiple-transverse-modes QSML, we observed the phenomenon of spatiotemporal dynamics that spatial patterns vary with the time.


The JNK inhibitor XG-102 protects against TNBS-induced colitis.
The c-Jun N-terminal kinase (JNK)-inhibiting peptide D-JNKI-1, syn. XG-102 was tested for its therapeutic potential in acute inflammatory bowel disease (IBD) in mice. Rectal instillation of the chemical irritant trinitrobenzene sulfonic acid (TNBS) provoked a dramatic acute inflammation in the colon of 7-9 weeks old mice. Coincident subcutaneous application of 100 µg/kg XG-102 significantly reduced the loss of body weight, rectal bleeding and diarrhoea. After 72 h, the end of the study, the colon was removed and immuno-histochemically analysed. XG-102 significantly reduced (i) pathological changes such as ulceration or crypt deformation, (ii) immune cell pathology such as infiltration and presence of CD3- and CD68-positive cells, (iii) the production of tumor necrosis factor (TNF)-α in colon tissue cultures from TNBS-treated mice, (iv) expression of Bim, Bax, FasL, p53, and activation of caspase 3, (v) complexation of JNK2 and Bim, and (vi) expression and activation of the JNK substrate and transcription factor c-Jun. A single application of subcutaneous XG-102 was at least as effective or even better depending on the outcome parameter as the daily oral application of sulfasalazine used for treatment of IBD.The successful and substantial reduction of the severe, TNBS-evoked intestinal damages and clinical symptoms render the JNK-inhibiting peptide XG-102 a powerful therapeutic principle of IBD.


[Use of selective media with lincomycin for the directed screening of antibiotic producers].
Relation between lincomycin resistance of Micromonospora cultures freshly isolated from soil samples and their capacity for production of antibiotics related to lincomycin by the structure or mode of action was shown. 32 cultures of Micromonospora were isolated from soil platings containing 50--100 microgram/ml of lincomycin. Crude antibiotic substances were recovered with the method of organic solvent extraction from 10 cultures possessing pronounced antibiotic activity. Selective inactivity (MIC more 1000 microgram/ml) of the crude substances with respect to the lincomycin resistant variant of Staph. aureus 209 p was observed, 2 of them having no inhibitory effect on the erythromycin resistant variant of the staphylococcus. The crude antibiotics inhibited the growth of the initial strain of the staphylococcus and its other antibiotic resistant variants in concentrations of 0.5--10 microgram/ml. It was demonstrated with the use of gas chromatography and mass spectrometry that one substance was lincomycin and 4 substances were known macrolides. Efficiency of the simple method of directed screening of antibiotics belonging to definite groups is indicated. Resistance of actinomycetes freshly isolated from natural substrates to various antibiotics is used as the criterion for antibiotic screening. The method provides detection of various antibiotics which are analogs in the structure or mode of action of the selecting antibiotic used for the screening.


Purification and some properties of nitrate reductase (EC 126.96.36.199) from Escherichia coli K12.
1. Nitrate reductase was purified 134-fold from Escherichia coli K12. The purification procedure involves the release by Triton X-100 of the enzyme from the cell envelope. i. The purified enzyme exists in aqueous solution either as a monomer (mol. wt. about 220 000) or as an associated form (probably a tetramer; mol.wt. about 880 000). 3. The purified enzyme has three subunits with apparent mol.wts. of 150 000, 67000 and 65000. An additional subunit of apparent mol.wt. 20000 is present in a haem-containing fraction that is also produced by the preparative procedure described. 4. None of the enzyme subunits is present in the cell envelope of cells grown in the absence of nitrate. 5. Reversible changes in the activity of nitrate reductase in vitro with FMNH2 as reductant can be induced under circumstances which are without effect on the reduced Benzyl Viologen-NO3-activity.


Training analysis and reanalysis in the development of the psychoanalyst.
A psychoanalyst faces the extraordinary demand of becoming instrumental in the psychoanalytic process. In the candidate's attempt to rise to that expectation, the first step is the training analysis. As the center-piece of psychoanalytic education, it is no ordinary analysis and bears special burdens intrinsic to its multiple functions and institutionalization. Recognizing the difficulties of both analytic education and analytic practice, Freud suggested that the analyst be periodically reanalyzed; for many, reanalysis is integral to their analytic development. Indeed, an analyst is actually never "made" but is always "in the making," developing and maturing in life and in practice. Reanalysis serves to focus elements of transference and resistance, rework defenses, facilitate more extensive regression in the service of the ego, deepen emotional integration, rework those elements of psychoanalysis itself that have been incorporated into defensive structure, and further the maturation of the analyzing instrument. If analysis is our most powerful mode of initial education, reanalysis is the most powerful form of continuing education. That remarkably little attention has been paid to reanalysis is testimony to the infantile fantasies that remain invested in our personal analyses.


Hospital service duplication: evidence on the medical arms race.
Hospital administrators face challenging decisions about whether to maintain, cut, or add services in response to changes in consumer demand or managed-care pressures. The challenge is heightened for services that are also offered by other hospitals in the local community. This study provides evidence on the financial effects of providing services that are also provided by other hospitals in the same county. Its purpose is to help guide administrators and policy makers in assessing the wisdom of service duplication at the local level. The unit of analysis is the individual hospital. The study reports data from the 2,204 general acute care hospitals located in counties with more than one hospital. A longitudinal path model is constructed for the years 1998, 2000, and 2002, with environmental and organizational factors from 1998 affecting service duplication in 2000, which in turn affects financial performance in 2002. Maximum likelihood estimation in linear structural relations is used to evaluate the path model and its coefficients. Hospital competition is associated with higher levels of duplication of inpatient, ancillary, and high-tech services. Duplication of inpatient services is associated with higher costs but also with higher operating margin. Duplication of ancillary services is associated with higher return on assets. Duplicated high-tech services are financial losers for hospitals. Higher levels of duplicated high-tech services are associated with higher cost per day, higher cost per discharge, and lower operating margin. From the standpoint of financial impact on the hospital, administrators should reexamine the costs and benefits of offering high-tech services that are offered by other providers in the local area. The higher costs may not be offset by revenues. Duplicated ancillary and inpatient services, on the other hand, produce some positive financial returns.


Effectiveness and Coverage of Treatment for Severe Acute Malnutrition Delivered by Community Health Workers in the Guidimakha Region, Mauritania.
Geographical and economic access barriers to health facilities (HF) have been identified as some of the most important causes of the low coverage of severe acute malnutrition (SAM) treatment. The objective of this study is to assess the effectiveness and coverage of SAM treatment delivered by community health workers (CHWs) in the Guidimakha region in Mauritania, compared to the HF based approach. This study was a nonrandomized controlled trial, including two rural areas. The control group received outpatient treatment for uncomplicated SAM from HF, whilst the intervention group received outpatient treatment for uncomplicated SAM from HF or CHWs. A total of 869 children aged 6-59 months with SAM without medical complications were included in the study. The proportion of cured children was 82.3% in the control group, and 76.4% in the intervention group, we found no significant difference between the groups. Coverage in the intervention zone increased from 53.6% to 71.7%. In contrast, coverage remained at approximately 44% in the control zone from baseline to end-line. This study is the first to demonstrate in Mauritania that the decentralization model of CHWs treating SAM improves acute malnutrition treatment coverage and complies with the international quality standards for community treatment of acute malnutrition. The non-randomized study design may limit the quality of the evidence, but these results could be used by political decision-makers as a first step in revising the protocol for acute malnutrition management.


Systematic engineering of uniform, highly efficient, targeted and shielded viral-mimetic nanoparticles.
In the past decades, numerous types of nanomedicines have been developed for the efficient and safe delivery of nucleic acid-based drugs for cancer therapy. Given that the destination sites for nucleic acid-based drugs are inside cancer cells, delivery systems need to be both targeted and shielded in order to overcome the extracellular and intracellular barriers. One of the major obstacles that has hindered the translation of nanotechnology-based gene-delivery systems into the clinic has been the complexity of the design and assembly processes, resulting in non-uniform nanocarriers with unpredictable surface properties and efficiencies. Consequently, no product has reached the clinic yet. In order to address this shortcoming, a multifunctional targeted biopolymer is genetically engineered in one step, eliminating the need for multiple chemical conjugations. Then, by systematic modulation of the ratios of the targeted recombinant vector to PEGylated peptides of different sizes, a library of targeted-shielded viral-mimetic nanoparticles (VMNs) with diverse surface properties are assembled. Through the use of physicochemical and biological assays, targeted-shielded VMNs with remarkably high transfection efficiencies (>95%) are screened. In addition, the batch-to-batch variability of the assembled targeted-shielded VMNs in terms of uniformity and efficiency is examined and, in both cases, the coefficient of variation is calculated to be below 20%, indicating a highly reproducible and uniform system. These results provide design parameters for engineering uniform, targeted-shielded VMNs with very high cell transfection rates that exhibit the important characteristics for in vivo translation. These design parameters and principles could be used to tailor-make and assemble targeted-shielded VMNs that could deliver any nucleic acid payload to any mammalian cell type.


Effects of diet and exercise on muscle and liver intracellular lipid contents and insulin sensitivity in type 2 diabetic patients.
Insulin resistance is associated with the circulating free fatty acid (FFA) level and intracellular lipid content in muscle and liver. We investigated the effect of 2-wk diet and exercise therapy on total adiposity, circulating FFA, intracellular lipid content in muscle and liver, and peripheral insulin sensitivity. Type 2 diabetic patients were divided into a diet group (n = 7) and a diet plus exercise group (n = 7). We performed a hyperinsulinemic-euglycemic clamp study before and after treatment. Intramyocellular lipid (IMCL) in the tibialis anterior muscle and intrahepatic lipid (IHL) were evaluated by (1)H-magnetic resonance spectroscopy. Fasting FFA were not altered, and total body fat showed a slight, but significant, decrease in both groups after treatment. IMCL was decreased by 19%, and the glucose infusion rate was increased by 57% in the diet plus exercise group, whereas neither IMCL nor glucose infusion rate was significantly altered in the diet group. However, IHL showed a significant decrease in both groups. In summary, we found that 2 wk of diet and exercise decreased IMCL and increased muscle insulin-mediated glucose uptake, whereas diet with or without exercise decreased IHL. These effects were evident despite a small decrease in body fat and were observed independently of fasting FFA levels.


Are Jamaicans really that stigmatizing? A comparison of mental health help-seeking attitudes.
Research suggests that there is a high level of stigma surrounding mental illness in the English-speaking Caribbean, limited knowledge about aetiology and scepticism about the effectiveness of treatment. Further, in spite of experiencing symptoms of distress, a growing body of literature has suggested that Caribbean nationals hold negative attitudes toward seeking professional psychological help. It has been suggested that these attitudes may be even more negative than for other populations. This paper presents the results of two studies which sought to examine this assumption. It was hypothesized that Jamaicans would hold more negative attitudes toward seeking professional mental health services than samples from other populations. Data regarding attitudes toward seeking professional psychological help were collected from 339 Jamaican adolescents. In study 1, a review of the literature was conducted. Three published studies that utilized the same measure of help-seeking attitudes, had a sample similar in age, and published their sample size, means and standard deviations, which were compared to the Jamaican sample. In study 2, data from the Jamaican sample were compared to a sample of African-American adolescents (n = 81). Results did not support the hypothesis. Jamaicans were generally found to be either similar or more positive in their attitudes toward seeking professional psychological help. These encouraging results are discussed. Suggestions for improving education and reducing mental health stigma are presented.


Transdermal delivery of gentamicin using dissolving microneedle arrays for potential treatment of neonatal sepsis.
Neonatal infections are a leading cause of childhood mortality in low-resource settings. World Health Organization guidelines for outpatient treatment of possible serious bacterial infection (PSBI) in neonates and young infants when referral for hospital treatment is not feasible include intramuscular gentamicin (GEN) and oral amoxicillin. GEN is supplied as an aqueous solution of gentamicin sulphate in vials or ampoules and requires health care workers to be trained in dose calculation or selection of an appropriate dose based on the patient's weight band and to have access to safe injection supplies and appropriate sharps disposal. A simplified formulation, packaging, and delivery method to treat PSBI in low-resource settings could decrease user error and expand access to lifesaving outpatient antibiotic treatment for infants with severe infection during the neonatal period. We developed dissolving polymeric microneedles (MN) arrays to deliver GEN transdermally. MN arrays were produced from aqueous blends containing 30% (w/w) of GEN and two polymers approved by the US Food and Drug Administration: sodium hyaluronate and poly(vinylpyrrolidone). The arrays (19×19 needles and 500μm height) were mechanically strong and were able to penetrate a skin simulant to a depth of 378μm. The MN arrays were tested in vitro using a Franz Cell setup delivering approximately 4.45mg of GEN over 6h. Finally, three different doses (low, medium, and high) of GEN delivered by MN arrays were tested in an animal model. Maximum plasma levels of GEN were dose-dependent and ranged between 2 and 5μg/mL. The time required to reach these levels post-MN array application ranged between 1 and 6h. This work demonstrated the potential of dissolving MN arrays to deliver GEN transdermally at therapeutic levels in vivo.


Characterizing attitudes toward maternal RSV vaccines among pregnant and lactating persons in Kenya: Key considerations for demand generation efforts for vaccine acceptance.
This study examined attitudes toward maternal RSV vaccines among pregnant and lactating persons in Kenya. First pregnancy was associated with higher vaccine hesitancy among pregnant and lactating people, and social norms were associated with higher vaccine hesitancy among lactating people. Understanding maternal RSV attitudes is critical for vaccine acceptance.


Inhibitory mechanism of epicatechin gallate on tyrosinase: inhibitory interaction, conformational change and computational simulation.
The inhibition mechanism of epicatechin gallate (ECG) on tyrosinase was investigated by multispectroscopic techniques combined with molecular docking and molecular dynamics simulation. The results demonstrated that ECG suppressed the activity of tyrosinase in a reversible mixed-inhibition with a half inhibitory concentration (IC50) of (1.13 ± 0.82) × 10-5 mol L-1. Binding of ECG to tyrosinase led to the formation of a complex with the binding constant (Ksv) of 4.03 × 104 L mol-1 at 298 K which was stabilized by hydrophobic forces. The complex formation induced the intrinsic fluorescence quenching and secondary structure change of tyrosinase. Molecular docking results showed that hydrophobic and hydrogen bonding forces played a dominant role in the binding of ECG to tyrosinase, affecting the binding affinity of l-dopa to tyrosinase, leading to a decrease in tyrosinase activity. Molecular dynamics analysis indicated that ECG led to the stretching of the basic framework structure of tyrosinase and slightly influenced the microenvironment of amino acid residues. The research might provide new perspectives on the inhibition mechanism of epicatechin gallate on tyrosinase and a theoretical basis for the prevention and treatment of pigmented skin diseases and anti-browning of catechin as a food supplement.


Leveraging Health Information Exchange to Construct a Registry for Traumatic Brain Injury, Spinal Cord Injury and Stroke in Indiana.
Traumatic brain injury (TBI), spinal cord injury (SCI) and stroke are conditions of interest to public health as they can result in long-term outcomes and disabilities. Specialized registries can facilitate public health surveillance, however only 4% of hospitals in the United States actively engage in electronic reporting to these registries. We leveraged electronic claims and clinical data from a health information exchange to create a statewide TBI/SCI/Stroke registry to facilitate the study of long-term outcomes and health services utilization. The registry contains 109,943 TBI patients, 9,027 SCI patients and 117,084 stroke patients with a mean of 3 years of follow-up data after injury. Additionally, the registry contains data on individual patient encounters, prescriptions and clinical variables. The high-dimensional data with large sample sizes may present a valuable informatics resource for injury research as well as public health surveillance.


Ferulic acid dimer as a non-opioid therapeutic for acute pain.
Search for alternate pain medications has gained more importance in the past few years due to adverse effects associated with currently prescribed drugs including nervous system dysfunction with opioids, gastrointestinal discomfort with nonsteroidal anti-inflammatory drugs, and cardiovascular anomalies with cyclooxygenase-2 (COX-2) inhibitors. Phytomedicine has been explored for the treatment of pain, as these have been used for generations in regional communities and tend to lack major side effects in general. One such phytomedicine, incarvillateine (INCA), derived from the Chinese herb Incarvillea sinensis has its primary antinociceptive action through the adenosine receptor, a novel pain target. We hypothesized that derivatives of cinnamic acid dimers, which are structurally similar to INCA, would show potent antinociceptive action and that their effect would be mediated through adenosine receptor action. Dimers of cinnamic acid (INCA analogs) were synthesized using cavitand-mediated photodimerization (CMP) method, which utilizes a macromolecule (γ-cyclodextrin) to control excited state reactivity of photoactive compounds. Acute pain response was assessed by using formalin-induced licking behavior in hind paw of mice, and neurologic function was monitored through locomotor activity, mechanical hyperalgesia, and thermal sensitivity upon administration of test compound. For mechanistic studies, binding to adenosine receptor was determined by using computer modeling. Ferulic acid dimer (FAD), which has the same chemical functionalities on the aromatic ring as INCA, showed significant suppression of formalin-induced acute pain. Antinociceptive effect was observed primarily in the inflammatory phase, and no apparent behavioral changes related to the nervous system were noticeable. Inhibition of opioid receptor did not reverse antinociceptive response, and modeling data suggest adenosine 3 receptor binding. FAD (INCA analog) shows potent nonopioid antinociceptive action mediated predominantly through A3AR - adenosine 3 receptor action. Further characterization and selection of such INCA analogs will help us generate a new class of antinociceptives with precise chemical modifications by using CMP methodology.


An open-label tolerability and efficacy study of an aluminum sesquichlorohydrate topical foam in axillary and palmar primary hyperhidrosis.
Primary hyperidrosis (PH) is a disorder characterized by excessive eccrine sweat gland production that primarily involves the axillae as well as palms and soles. Common first-line topical treatment for PH consists of aluminum salts (AS) that act by physically blocking eccrine sweat gland ducts. However, primary irritant contact dermatitis is a common side effect of AS treatment. Recently, a new low-residue, thermophobic foam formulation containing 20% aluminum sesquichlorohydrate has been developed (Nidrox, Mipharm S.p.A.). To evaluate the local tolerability and efficacy of 20% aluminum sesquichlorohydrate foam in the treatment of axillary and palmar PH. Twenty subjects affected by PH were enrolled in a multicenter, open-label study. Local tolerability was evaluated by physicians assessing itching, burning, and skin irritation using a four-point score (from 0: no symptoms to 3: severe symptoms). Skin irritation was quantified with a visual score. Efficacy was assessed by means of Minor test score using a four-point score (range 0-3). The foam was applied to clean dry skin, every night during the first 2 weeks and three times a week during the following 2 weeks. Clinical evaluations were performed at baseline, at day 14 and at day 28. Patients were monitored throughout the study for adverse events. All 20 subjects completed the study. The foam induced a significant reduction of the Minor score in comparison with baseline values (p = 0.0002) both at day 14 and at day 28. At the end of the 4-week treatment period, the foam reduced eccrine sweating by 61% (Minor score: 3.3 vs. 8.5). No skin irritation was observed during the trial except for one subject who experienced a mild and transient itching sensation. No other side effects were reported during the study. This new foam appears to be an effective and well-tolerated topical treatment in reducing sweating in patients with axillary and palmar PH.


[Reference limits for urine sediments performed on Sysmex UF-50].
The Sysmex UF-50 is an automated flow cytometer for urine sediments analysis. Interpretation of the results needs establishment of reference limits for the different constituents measured. First of all, we checked precision of measurements and stability of urines during transportation. Then, urine samples from 4 to 95 year old subjects were examined with the UF-50, by visual microscopy and test strips. Distributions of results for erythrocytes, leukocytes, epithelial cells, casts, bacteria and conductivity were described in a sample of 680 subjects (364 men and 316 women), with creatininemia below 140 micromol/L, consuming no drugs and for women without intra uterine device and apart from menstruation period. Then, the results were compared with those obtained in groups selected on microscopic analysis and test strip results. UF-50 sensitivity and specificity were 77.5% and 88% for 15 erythrocytes/microL in reference to microscopic urinalysis, they were 91.3% and 87.3% for 15 leucocytes/microL. The reference sample was defined with negative microscopic results. The upper reference limits (centile 97.5) were 16 red blood cells/microL for men 14.5 for women, 13.5 and 33 leucocytes/microL, 8 and 19 epithelial cells/microL, 1,3 and 0,4 casts/microL, 5 500 et 7 700 bacteria/microL, 36,2 et 34,6 conductivity mS/cm. The Sysmex UF-50 is a suitable analyser for urinary sediments. Reference limits may be different from usual reference limits due to variability in performances of other methods.


Stroke in American Indians and Alaska Natives: A Systematic Review.
We conducted a systematic review of published studies on stroke epidemiology in American Indians and Alaska Natives (AI/ANs). We used MeSH terms and strict inclusion criteria to search PubMed, identifying a relevant sample of 57 refereed publications. We report a consensus view in which prevalent stroke is more common, and estimates of cerebrovascular risk factors are higher, among AI/ANs than among other US populations. Like other minority groups, AI/ANs suffer stroke at younger ages than do non-Hispanic Whites. However, data on AI/AN stroke mortality are significantly compromised by racial misclassification and nonrepresentative sampling. Studies correcting for these problems have found that stroke mortality rates among AI/ANs are among the highest of all US racial and ethnic groups. As with Black and non-Hispanic White stroke mortality, AI/AN stroke mortality varies by geographic region, with the highest rates in Alaska and the Northwest and the lowest in the Southwest. Our results underscore the need for a concerted national effort to collect accurate cross-sectional and longitudinal data on stroke in AI/ANs.


Getting the nod: Pediatric head motion in a transdiagnostic sample during movie- and resting-state fMRI.
Head motion continues to be a major problem in fMRI research, particularly in developmental studies where an inverse relationship exists between head motion and age. Despite multifaceted and costly efforts to mitigate motion and motion-related signal artifact, few studies have characterized in-scanner head motion itself. This study leverages a large transdiagnostic public dataset (N = 1388, age 5-21y, The Healthy Brain Network Biobank) to characterize pediatric head motion in space, frequency, and time. We focus on practical aspects of head motion that could impact future study design, including comparing motion across groups (low, medium, and high movers), across conditions (movie-watching and rest), and between males and females. Analyses showed that in all conditions, high movers exhibited a different pattern of motion than low and medium movers that was dominated by x-rotation, and z- and y-translation. High motion spikes (>0.3mm) from all participants also showed this pitch-z-y pattern. Problematic head motion is thus composed of a single type of biomechanical motion, which we infer to be a nodding movement, providing a focused target for motion reduction strategies. A second type of motion was evident via spectral analysis of raw displacement data. This was observed in low and medium movers and was consistent with respiration rates. We consider this to be a baseline of motion best targeted in data preprocessing. Further, we found that males moved more than, but not differently from, females. Significant cross-condition differences in head motion were found. Movies had lower mean motion, and especially in high movers, movie-watching reduced within-run linear increases in head motion (i.e., temporal drift). Finally, we used intersubject correlations of framewise displacement (FD-ISCs) to assess for stimulus-correlated motion trends. Subject motion was more correlated in movie than rest, and 8 out of top 10 FD-ISC windows had FD below the mean. Possible reasons and future implications of these findings are discussed.


Comparison of the PU.1 transcriptional regulome and interactome in human and mouse inflammatory dendritic cells.
Dendritic cells (DCs) are key immune modulators and are able to mount immune responses or tolerance. DC differentiation and activation imply a plethora of molecular and cellular responses, including transcriptional changes. PU.1 is a highly expressed transcription factor in DCs and coordinates relevant aspects of DC biology. Due to their role as immune regulators, DCs pose as a promising immunotherapy tool. However, some of their functional features, such as survival, activation, or migration, are compromised due to the limitations to simulate in vitro the physiologic DC differentiation process. A better knowledge of transcriptional programs would allow the identification of potential targets for manipulation with the aim of obtaining "qualified" DCs for immunotherapy purposes. Most of the current knowledge regarding DC biology derives from studies using mouse models, which not always find a parallel in human. In the present study, we dissect the PU.1 transcriptional regulome and interactome in mouse and human DCs, in the steady state or LPS activated. The PU.1 transcriptional regulome was identified by performing PU.1 chromatin immunoprecipitation followed by high-throughput sequencing and pairing these data with RNAsequencing data. The PU.1 interactome was identified by performing PU.1 immunoprecipitation followed by mass spectrometry analysis. Our results portray PU.1 as a pivotal factor that plays an important role in the regulation of genes required for proper DC activation and function, and assures the repression of nonlineage genes. The interspecies differences between human and mouse DCs are surprisingly substantial, highlighting the need to study the biology of human DCs.


Socio-economic characteristics in children with coeliac disease.
To study the relationship between socio-economic factors and coeliac disease. This study was part of a prospective cohort study of 16 286 children born from 1 October 1997-1 October 1999 (the ABIS study; All Babies in Southeast Sweden). Eight paediatric departments recorded all children with coeliac disease in southeast Sweden. Coeliac disease was confirmed through biopsy. Socio-economic characteristics (maternal employment, civil status, whether parents were born in Sweden, parental education, place of living before pregnancy and during pregnancy, crowded living), infant sex, previous siblings, parental age and maternal alcohol consumption during pregnancy were analysed using logistic regression. All data, except for those related to diagnosis of coeliac disease, were obtained through a questionnaire distributed at birth. Coeliac disease in the offspring was less common among mothers who had worked < 3 mo during pregnancy (odds ratio, OR = 0.29; 95% CI: 0.09-0.94; p = 0.039). This risk decrease remained after adjustment for confounders (adjusted OR = 0.28; 95% CI: 0.09-0.92; p = 0.035). No other socio-economic factor was related to coeliac disease. This study indicates that most socio-economic factors are probably of little importance to the development of coeliac disease.


Development of algae-bacteria granular consortia in photo-sequencing batch reactor.
The development and properties of algae-bacteria granular consortia, which cultivated with the algae (Chlorella and Scenedesmus) and aerobic granules, was investigated in this experiment. The results indicated that the granular consortia could be successfully developed by selection pressure control, and the algal biomass and extracellular polymeric substances (EPS) concentration in the consortia showed notable correlation with the operating parameters of reactor. The maximum specific removal rates of total nitrogen and phosphate were obtained from the granular consortia with the highest algal biomass, yet the correlation between the fatty acid methyl esters yield and the algal biomass in the consortia was not markedly observed. The seed algae maintained dominance in the phototroph community, whereas the cyanobacteria only occupied a small proportion (5.2-6.5%). Although the bacterial communities with different operational strategies showed significant difference, the dominated bacteria (Comamonadaceae, 18.79-36.25%) in the mature granular consortia were similar.


Interpretable Molecular Property Predictions Using Marginalized Graph Kernels.
Marginalized graph kernels have shown competitive performance in molecular machine learning tasks but currently lack measures of interpretability, which are important to improve trust in the models, detect biases, and inform molecular optimization campaigns. We here conceive and implement two interpretability measures for Gaussian process regression using a marginalized graph kernel (GPR-MGK) to quantify (1) the contribution of specific training data to the prediction and (2) the contribution of specific nodes of the graph to the prediction. We demonstrate the applicability of these interpretability measures for molecular property prediction. We compare GPR-MGK to graph neural networks on four logic and two real-world toxicology data sets and find that the atomic attribution of GPR-MGK generally outperforms the atomic attribution of graph neural networks. We also perform a detailed molecular attribution analysis using the FreeSolv data set, showing how molecules in the training set influence machine learning predictions and why Morgan fingerprints perform poorly on this data set. This is the first systematic examination of the interpretability of GPR-MGK and thereby is an important step in the further maturation of marginalized graph kernel methods for interpretable molecular predictions.


The emotional valence of a conflict: implications from synesthesia.
According to some synesthetes' reports, their experience involves an emotional sensation in which a conflict between the photism and presented color of a stimulus may evoke a feeling of discomfort. In order to investigate the impact of this experience on performance, two experiments were carried out on two synesthetes and their matched control groups. Experiments were tailored for each synesthete according to her unique photism. Participants were presented with stimuli (numerals or words) in colors and were asked to name the color of the stimulus and to ignore its meaning. Incongruent colors were associated with negative or positive emotional words or with non-emotional words. Not surprisingly, an incongruent color (e.g., 5 presented in yellow to a synesthete that sees 5 in red) slowed down color naming. Conflict situations (e.g., a numeral in an incongruent color) created a negative emotional experience. Most importantly, coherence between a conflict or non-conflict emotional experience and the emotion elicited by the color of the stimulus for a given synesthete modulated performance. In particular, synesthetes were faster in coherent than in incoherent situations. This research contributes to the understanding of emotional experience in synesthesia, and also suggests that synesthesia can be used as an instrument to investigate emotional processes in the wider population.


Combined non-invasive assessment of endothelial shear stress and molecular imaging of inflammation for the prediction of inflamed plaque in hyperlipidaemic rabbit aortas.
To evaluate the incremental value of low endothelial shear stress (ESS) combined with high-resolution magnetic resonance imaging (MRI)- and computed tomography angiography (CTA)-based imaging for the prediction of inflamed plaque. Twelve hereditary hyperlipidaemic rabbits underwent quantitative analysis of plaque in the thoracic aorta with 256-slice CTA and USPIO-enhanced (ultra-small superparamagnetic nanoparticles, P904) 1.5-T MRI at baseline and at 6-month follow-up. Computational fluid dynamics using CTA-based 3D reconstruction of thoracic aortas identified the ESS patterns in the convex and concave curvature subsegments of interest. Subsegments with low baseline ESS exhibited significant increase in wall thickness and plaque inflammation by MRI, in non-calcified plaque burden by CTA, and developed increased plaque size, lipid and inflammatory cell accumulation (high-risk plaque features) at follow-up by histopathology. Multiple regression analysis identified baseline ESS and inflammation by MRI to be independent predictors of plaque progression, while receiver operating curve analysis revealed baseline ESS alone or in combination with inflammation by MRI as the strongest predictor for augmented plaque burden and inflammation (low ESS at baseline: AUC = 0.84, P < 0.001; low ESS and inflammation by molecular MRI at baseline: AUC = 0.89, P < 0.001). Low ESS predicts progression of plaque burden and inflammation as assessed by non-invasive USPIO-enhanced MRI. Combined non-invasive assessment of ESS and imaging of inflammation may serve to predict plaque with high-risk features.


The Influence of Age, Health Literacy, and Affluence on Adolescents' Capacity to Consent to Research.
While adults are assumed to have the capacity to consent to medical research, and young children to have no capacity, adolescents' capacity to consent is not well described. Adapting the MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR), we describe adolescents' capacity to consent to medical research and factors influencing that capacity. Our pilot study included a community-based sample of 30 adolescents, 14 to 21 years of age, who completed the MacCAT-CR after undergoing a simulated informed consent process. We found that adolescents' capacity to consent to research was associated with age, health literacy, and family affluence. These findings suggest that investigators and institutional review boards should be aware that factors other than age may influence capacity to consent, and, for modifiable factors, such as health literacy, consent processes for medical research with adolescents can be modified.


Unilateral spermatic cord torsion without ipsilateral spermatogenetic material: effects on testicular blood flow and fertility potential.
This experiment was planned to answer the question of how the elimination of ipsilateral spermatogenetic material, which is necessary for contralateral testicular damage caused by an autoimmune response, affects contralateral testicular blood flow and fertility potential in unilateral spermatic cord torsion (USCT). Thirty-four male and 68 female adult albino rats were divided into three groups. Group 1 rats underwent a control operation, group 2 rats underwent subepididymal orchiectomy to eliminate spermatogenetic material, and group 3 rats underwent USCT after subepididymal orchiectomy. Testicular blood flows of the rats were measured by (133)Xe clearance technique. Additionally, to determine fertility potential, each male rat was housed with two female rats. Numbers of impregnated and delivered rats were recorded. Both mean testicular blood flow and fecundity of group 3 were significantly lower than those of groups 1 and 2. When compared with groups 1 and 2, fertility and mean number of the impregnated rats of group 3 were lower but the differences were not significant. These findings suggest that absence of spermatogenetic material in USCT reduces contralateral blood flow and fertility potential. Therefore, contralateral testicular damage originating from blood flow alterations rather than autoimmune mechanism should be considered to explain fertility problems encountered following USCT.


Highly Potent and Selective Butyrylcholinesterase Inhibitors for Cognitive Improvement and Neuroprotection.
Butyrylcholinesterase (BChE) has been considered as a potential therapeutic target for Alzheimer's disease (AD) because of its compensation capacity to hydrolyze acetylcholine (ACh) and its close association with Aβ deposit. Here, we identified S06-1011 (hBChE IC50 = 16 nM) and S06-1031 (hBChE IC50 = 25 nM) as highly effective and selective BChE inhibitors, which were proved to be safe and long-acting. Candidate compounds exhibited neuroprotective effects and the ability to improve cognition in scopolamine- and Aβ1-42 peptide-induced cognitive deficit models. The best candidate S06-1011 increased the level of ghrelin, a substrate of BChE, which can function as improving the mental mood appetite. The weight gain of the S06-1011-treated group remarkably increased. Hence, BChE inhibition not only plays a protective role against dementia but also exerts a great effect on treating and nursing care.


Switching exponent scaling near bifurcation points for non-Gaussian noise.
We study noise-induced switching of a system close to bifurcation parameter values where the number of stable states changes. For non-Gaussian noise, the switching exponent, which gives the logarithm of the switching rate, displays a non-power-law dependence on the distance to the bifurcation point. This dependence is found for Poisson noise. Even weak additional Gaussian noise dominates switching sufficiently close to the bifurcation point, leading to a crossover in the behavior of the switching exponent.


Supraorbital transciliary keyhole approach for removal of tuberculum sellae meningioma: 3D surgical video.
Tuberculum sellae meningiomas have an incidence from 5 to 10% of all intracranial meningiomas[2] and tend to be surgically difficult and challenging tumors given their proximity to important structures such as the internal carotid artery (ICA), anterior cerebral artery (ACA), and optic nerves.[3] Typically, their growth is posteriorly and superiorly oriented, thereby displacing the optic nerves and causing visual dysfunction, which is the primary indication for surgical treatment.[1] The main goals of the treatment are the preservation or restoration of visual abilities and a complete tumor resection.[1] Conventionally, surgical approaches to tuberculum meningiomas involve largely invasive extended bifrontal, interhemispheric, orbitozygomatic, pterional, and subfrontal eyebrow approaches. The supraorbital craniotomy, however, is a minimally invasive transcranial approach that offers a similar surgical corridor to conventional transcranial approaches, using a limited craniotomy and minimal brain retraction that can be used for tumoral and vascular pathologies,[4,5] offering added cosmetic outcomes.[1] We present the case of a patient undergoing a supraorbital transciliary craniotomy with a tuberculum sellae meningioma causing bitemporal hemianopsia. A 70-year-old female with chronic headaches and progressive vision loss and visual field deficit for about 1 year. On ophthalmological evaluation, she was able to fixate and follow objects with each eye, light perception was only present in the right eye, and the vision in the left eye was 0.2 decimal units. Her visual fields demonstrated severe campimetric deficits. Her extraocular movements were intact and bilateral pupils were equal, round, and reactive to light. MRI of the brain demonstrated tuberculum sellae meningioma with bilateral optic canal invasion, displacing the chiasm, and extending ≥180° around the medial ICA wall and anterior ACA wall. The patient underwent supraorbital transciliary keyhole approach for total resection of the tumor. Postoperatively, visual acuity and visual field were significantly improved. Performing a supraorbital transciliary keyhole craniotomy for tuberculum sellae meningiomas requires an adequate and meticulous preoperative planning to determine the optimal surgical corridor to the lesion. The use of supraorbital craniotomy is safe with good cosmetic results and potentially lower morbidity allowing for adequate exposure, resection, and release of neurovascular structures.


Pyogenic vertebral osteomyelitis: diagnosis and management.
Vertebral osteomyelitis represents a diagnostic challenge to the clinician. Two cases of pyogenic vertebral osteomyelitis occurring weeks to months after a urinary tract infection with Escherichia coli are described. The rarity and subtle clinical presentation of this condition, the presence of pre-existing degenerative arthritic changes, and delayed appearance of radiologic signs of progression to destructive osteomyelitis contributed to a significant delay in diagnosis. Increased awareness of vertebral osteomyelitis as a clinical entity combined with information from radionuclide scanning may permit earlier detection of this condition.


The Care-coordination Approach to Learning Lupus Self-Management: a patient navigator intervention for systemic lupus inpatients.
The Care-coordination Approach to Learning Lupus Self-Management (CALLS) study was designed to improve SLE disease self-management. This study aims to assess the benefits of the intervention compared with existing lupus care. Participants were randomly assigned to participate in 12-weekly phone sessions with the patient navigator that included structured educational content, care coordination and patient-centred support services, or a usual care control condition. Validated measures of health literacy, self-efficacy, patient activation and disease activity were collected. We used least squares means and linear mixed-effects regression models for each outcome variable to assess the changes in outcome, from baseline to postintervention and to estimate the difference in these changes between the intervention and control group. Thirty participants were enrolled and 14 were randomised to the treatment group. For perceived lupus self-efficacy, there was a significant increase in mean score for the intervention group, but not for the control group. With regard to disease activity, the experimental group experienced a slight decrease in mean flare score in the previous 3 months, whereas the control group experienced a slight increase, but this finding did not reach statistical significance. Trends were similar in self-reported global disease activity, but none of the findings were significant. Health literacy and patient activation measure scores remained largely unchanged throughout the study for the two groups. These findings suggest that the CALLS intervention may work to improve aspects of SLE disease self-management. Future research will be needed to validate these findings long-term. NCT04400240.


Concomitant exposure to air pollution, green space and noise, and risk of myocardial infarction. A Cohort study from Denmark.
The three correlated environmental exposures: air pollution, road traffic noise, and green space have all been associated with the risk of myocardial infarction (MI). The present study aimed to analyse their independent and cumulative association with MI. In a cohort of all Danes aged 50 or older in the period 2005 to 2017, five-year time-weighted average exposure to fine particles (PM2.5), ultrafine particles, elemental carbon, nitrogen dioxide (NO2), and road traffic noise at the most and least exposed façades of residence was estimated. Green space around residences was estimated from land use maps. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% interval (CI), and cumulative risk indices (CRI) were calculated. All expressed per inter quartile range. Models were adjusted for both individual and neighbourhood-level sociodemographic covariates. The cohort included 1,964,702 persons. During follow-up, 71,285 developed MI. In single-exposure models, all exposures were associated with an increased risk of MI. In multipollutant analyses, an independent association with risk of MI was observed for PM2.5 (HR: 1.026, 95% CI: 1.002-1.050), noise at most exposed façade (HR: 1.024, 95% CI: 1.012-1.035) and lack of green space within 150 m of residence (HR: 1.018, 95% CI: 1.010-1.027). All three factors contributed significantly to the CRI (1.089, 95% CI: 1.076-1.101). In a nationwide cohort study, air pollution, noise and lack of green space were all independently associated with an increased risk of MI. The air pollutant PM2.5 was closest associated with MI risk.


Diabetes and risk of endometrial cancer: a population-based prospective cohort study.
Although there is accumulating evidence that hyperinsulinemia in the context of insulin resistance is associated with carcinogenesis, only one prospective study of endometrial cancer incidence, in relation to diabetes, addressed this issue and showed no significant positive association. No previous study has investigated whether physical activity can modify the association between diabetes and endometrial cancer. We examined the association between diabetes and incidence of endometrial cancer and the potential effect modification by obesity and physical activity in the Swedish Mammography Cohort, a prospective cohort of 36,773 women, including 225 incident endometrial adenocarcinoma cases. After adjustments, the relative risk (RR) for endometrial cancer among women with diabetes comparing with nondiabetic women was 1.94 [95% confidence interval (95% CI), 1.23-3.08]. Among obese diabetics, the RR was 6.39 (95% CI, 3.28-12.06) compared with nonobese nondiabetic women. Among diabetics with low physical activity, the RR for endometrial cancer was 2.80 (95% CI, 1.62-4.85) compared with physically active nondiabetic women. Obese diabetics with low physical activity had a RR of 9.61 (95% CI, 4.66-19.83) compared with normal weight nondiabetic women with high physical activity. Diabetes was associated with a 2-fold increased risk, and combination of diabetes with obesity and low physical activity was associated with a further increased risk for endometrial cancer. Interventions to reduce body weight and increase physical activity may have important implications in terms of prevention of endometrial cancer and future management of diabetic subjects.


[Effect of risk factors and therapy on intermediate-term hip deformity in Perthes disease].
The prognostication of risk factors for the outcome of LCPD was examined. The radiographic results of conservative treatment with Thomas splint and operative treatment with intertrochanteric derotational varus osteotomy (DVO) were compared using the Index of Deformity (D). Radiographs of 153 patients with unilateral LCPD were evaluated retrospectively 1.5-3 years and 3-7 years after diagnosis using the Index of Deformity and Index of Direction. We investigated the radiographic changes in relation to acetabular or metaphyseal reaction, Waldenström classification or limited range of motion at diagnosis and in dependence of therapy. There was a significant better acetabulum-head-index of deformity after DVO. Children with metaphyseal or acetabular reaction had bigger deformities. Patients with metaphyseal reaction had smaller deformities after DVO compared with conservative treatment. Free range of motion (ROM) was prerequisite for good results after DVO. Waldenström classification at diagnosis did not have any influence on morphologic changes after 3-7 years. DVO leads to a better containment than conservative treatment with Thomas splint, metaphyseal reaction should be an indication for operative treatment. Prerequisite for DVO is a free ROM. Because Waldenström class at diagnosis does not influence the outcome, free ROM before starting the treatment is more important than an immediate start of therapy.


Enhancing school asthma action plans: qualitative results from southeast Minnesota beacon stakeholder groups.
This study explores ways southeast Minnesota schools currently address asthma problems, identifies areas for improvement, and assesses the potential value of asthma action plans (AAPs) in schools. Focus groups were used to query stakeholder groups on asthma care in schools. Groups were held separately for elementary school personnel, parents of elementary school children with asthma, and health professionals (N = 103). Transcripts were analyzed by hand and by using NVivo 9 software. Overall 103 stakeholders participated in focus groups. Major themes were (1) Communication; no uniform way of exchanging information between schools and health professionals. (2) Asthma Control Continuum; students require individualized instructions and information related to their asthma care. (3) Policy/Protocol; school staff roles and rules vary and are unclear. (4) Self-Reliance; older children self-manage their asthma and are unknown until they need emergent support. Solution recommended included AAPs used systematically with a method to communicate back from schools to physicians and parents. The AAP may solve several of the school's concerns regarding their ability to provide asthma support in school. However, the AAP must reach the school, and that is currently not happening. In addition, schools would like tools and systems to assess asthma control and share information back with parents and physicians.


Application of Molecular Dynamics Simulations in Molecular Property Prediction I: Density and Heat of Vaporization.
Molecular mechanical force field (FF) methods are useful in studying condensed phase properties. They are complementary to experiment and can often go beyond experiment in atomic details. Even a FF is specific for studying structures, dynamics and functions of biomolecules, it is still important for the FF to accurately reproduce the experimental liquid properties of small molecules that represent the chemical moieties of biomolecules. Otherwise, the force field may not describe the structures and energies of macromolecules in aqueous solutions properly. In this work, we have carried out a systematic study to evaluate the General AMBER Force Field (GAFF) in studying densities and heats of vaporization for a large set of organic molecules that covers the most common chemical functional groups. The latest techniques, such as the particle mesh Ewald (PME) for calculating electrostatic energies, and Langevin dynamics for scaling temperatures, have been applied in the molecular dynamics (MD) simulations. For density, the average percent error (APE) of 71 organic compounds is 4.43% when compared to the experimental values. More encouragingly, the APE drops to 3.43% after the exclusion of two outliers and four other compounds for which the experimental densities have been measured with pressures higher than 1.0 atm. For heat of vaporization, several protocols have been investigated and the best one, P4/ntt0, achieves an average unsigned error (AUE) and a root-mean-square error (RMSE) of 0.93 and 1.20 kcal/mol, respectively. How to reduce the prediction errors through proper van der Waals (vdW) parameterization has been discussed. An encouraging finding in vdW parameterization is that both densities and heats of vaporization approach their "ideal" values in a synchronous fashion when vdW parameters are tuned. The following hydration free energy calculation using thermodynamic integration further justifies the vdW refinement. We conclude that simple vdW parameterization can significantly reduce the prediction errors. We believe that GAFF can greatly improve its performance in predicting liquid properties of organic molecules after a systematic vdW parameterization, which will be reported in a separate paper.


Brain tissue adaptability to slow-growing tumors: case report of clivus meningioma.
A 46-year-old female patient with a large slow-growing craniocervical junction tumor is presented. Her complaints began 6 months before with sensory and painful sensations, sphincter impairment, and motor events (spastic tetraparesis, more pronounced on the left extremities). Magnetic resonance of the head revealed a rounded tumor of 2.5 cm in diameter, by its characteristics corresponding to meningioma, at the level of C1 vertebra and craniocervical junction, with the base at spinal canal anterior wall, occupying most of the craniocervical junction, compressing spinal cord and medulla oblongata. Intracerebral computed tomography angiography showed spared lumen and a satisfactory image of vertebral arteries bypassing the expansive growth at the occipital foramen, confirming slow tumor growth. Antiedematous therapy led to transient improvement in extremity strength and partial recovery of neurologic deficit, which resolved completely upon neurosurgical operation and rehabilitation. This case report exemplifies brain adaptability to slowly growing expansive neoplasms, based on its volume reduction up to the moment when further adaptation is not possible anymore, i.e. breaking of the mechanism of adaptation. Because of brain adaptability, such slowly growing tumors may stay asymptomatic for a long time. Brain plasticity also includes adaptation and autoregulation of the circulation, thus ensuring stable blood flow.


Inhaled budesonide in chronic bronchitis. Effects on respiratory impedance.
In a placebo controlled study the effects of 6 weeks' treatment with inhaled budesonide (1.6 mg daily) on the impedance of the respiratory system, spirometry and symptom scores were evaluated in 35 patients with chronic bronchitis with forced expiratory volume in one second (FEV1) greater than or equal to 70% predicted. Thirty patients completed the study. No statistically significant differences in the changes in morning peak expiratory flow rate (PEFR), symptom scores, use of terbutaline rescue medication and FEV1 were found between the placebo and the active treatment group. Budesonide treatment was found to result in a small decrease in resonant frequency and a less negative frequency dependence of resistance compared with the placebo group.


Effect of vitamin D and inhaled corticosteroid treatment on lung function in children.
Low vitamin D levels are associated with asthma and decreased airway responsiveness. Treatment with inhaled corticosteroids improves airway responsiveness and asthma control. To assess the effect of vitamin D levels on prebronchodilator FEV(1), bronchodilator response, and responsiveness to methacholine (PC(20), provocative concentration of methacholine producing a 20% decline in FEV(1)) in patients with asthma treated with inhaled corticosteroids. We measured 25-hydroxyvitamin D levels in the serum of children with persistent asthma at the time of enrollment in the Childhood Asthma Management Program. We divided subjects into the vitamin D sufficiency (>30 ng/ml), insufficiency (20-30 ng/ml), and deficiency (<20 ng/ml) groups. Covariates included age, treatment, sex, body mass index, race, history of emergency department visits, hospitalizations, and season that vitamin D specimen was drawn. Our main outcome measures were change in prebronchodilator FEV(1), bronchodilator response, and PC(20) from enrollment to 8-12 months. Of the 1,024 subjects, 663 (65%) were vitamin D sufficient, 260 (25%) were insufficient, and 101 (10%) were deficient. Vitamin D-deficient subjects were more likely to be older, African American, and have a higher body mass index compared with the vitamin D-sufficient and insufficient subjects. In the inhaled corticosteroid treatment group, prebronchodilator FEV(1) increased from randomization to 12 months by 140 ml in the vitamin D-deficient group and prebronchodilator FEV(1) increased by 330 ml in the vitamin D insufficiency group and by 290 ml in the vitamin D sufficiency group (P = 0.0072), in adjusted models. In children with asthma treated with inhaled corticosteroids, vitamin D deficiency is associated with poorer lung function than in children with vitamin D insufficiency or sufficiency.


Hyperthermophilic and salt-dependent formyltransferase from Methanopyrus kandleri.
Methanopyrus kandleri is a hyperthermophilic methanogenic archaeon, which grows on H(2) and CO(2) as its sole energy source. Its growth temperature optimum is 98 degrees C. One of the interesting characteristics of this archaeon is its high intracellular salt content. The organism has been reported to contain the trianionic cDPG (cyclic 2,3-diphosphoglycerate) and K+ at concentrations of 1.1 and 3 M, respectively. Reflecting the high cellular salt concentration, the enzymes in this organism are adapted not only to high temperature but also to high salt concentrations. The formyltransferase from M. kandleri was characterized extensively with respect to thermo- and halophilicity. The crystal structure of the formyltransferase at 1.73 A shows the enzyme to be composed of four identical subunits of molecular mass 32 kDa. The formyltransferase is thermostable and active only at relatively high concentrations of potassium phosphate (1 M) or other salts with strongly hydrated anions (strong salting-out salts). Potassium phosphate and potassium cDPG were found to be equivalent in activating and stabilizing the enzyme. At low concentrations of these salts, the enzyme is inactive and thermolabile. It was shown by equilibrium sedimentation analysis that the enzyme is in a monomer/dimer/tetramer equilibrium, the equilibrium constant being dependent on the concentration of salts: the higher oligomeric species increase with increasing salt concentrations. Evidence was provided that the monomer is both inactive and thermolabile. Experiments using a mutation which is directed to break surface ion pairs between two dimers indicated that dimerization is required for activity and tetramerization leads to thermostability.


Inhibition of two temporal phases of HIV-1 transfer from primary Langerhans cells to T cells: the role of langerin.
Epidermal Langerhans cells (eLCs) uniquely express the C-type lectin receptor langerin in addition to the HIV entry receptors CD4 and CCR5. They are among the first target cells to encounter HIV in the anogenital stratified squamous mucosa during sexual transmission. Previous reports on the mechanism of HIV transfer to T cells and the role of langerin have been contradictory. In this study, we examined HIV replication and langerin-mediated viral transfer by authentic immature eLCs and model Mutz-3 LCs. eLCs were productively infected with HIV, whereas Mutz-3 LCs were not susceptible because of a lack of CCR5 expression. Two successive phases of HIV viral transfer to T cells via cave/vesicular trafficking and de novo replication were observed with eLCs as previously described in monocyte-derived or blood dendritic cells, but only first phase transfer was observed with Mutz-3 LCs. Langerin was expressed as trimers after cross-linking on the cell surface of Mutz-3 LCs and in this form preferentially bound HIV envelope protein gp140 and whole HIV particles via the carbohydrate recognition domain (CRD). Both phases of HIV transfer from eLCs to T cells were inhibited when eLCs were pretreated with a mAb to langerin CRD or when HIV was pretreated with a soluble langerin trimeric extracellular domain or by a CRD homolog. However, the langerin homolog did not inhibit direct HIV infection of T cells. These two novel soluble langerin inhibitors could be developed to prevent HIV uptake, infection, and subsequent transfer to T cells during early stages of infection.


[Incidence of digestive system neoplasms. Trends. Soria 1981-1990].
The aim of this study was to evaluate, to compare and to identify the various incidence rate trends in digestive tract malignant tumours in the province of Soria. Tumor sites and histological types, patient's age, sex and town and area residence were studied. All new cases of digestive tract malignant tumours were collected during the 1981-1990 period. 30.4% of all malignant tumours in men (1906 patients) and 29% in women (1,256 patients) came from digestive tract sites. Incidence rates for each site were calculated for the two 1981-1985 and 1986-1990 subperiods. The histology, rates and trends of the tumours were compared with the other national and international cancer registries. Gastric cancer showed the highest adjusted rate for men (35.1 x 10(5) and colo-rectal cancer one for women (14.7 x 10(5). The lowest rates were for men in the gallbladder (0.5) and liver (1.1) sites; and for women in the gallbladder (1.6), whose diminishing trend was significant (2.92/0.75) (p < 0.05) and liver (0.5). Colorectal cancer showed a marked increase between the two subperiods for both sexes (men: 13.1/27.6) (women: 9.8/19.2). Pancreas cancer trends ascended for both sexes (men: 1.22/2.74) (women: 0.13/1.46). Gastric cancer rates in Soria are higher than the rest of the cancer registries in Spain while gallbladder, liver, and colorectal, cancer rates are one of the lowest for both sexes. Trends are significantly increasing in colorectal sites for both sexes (p < 0.01), and for women only in the pancreas (p < 0.05). The other cancer rate sites showed lesser variations and are not statistically significant.


Assessment of scleral spur visibility with anterior segment optical coherence tomography.
To develop a grading system to evaluate the scleral spur visibility and to investigate the association between this and the angle width. Sixty healthy normal subjects (33 with open angles and 27 with narrow angles on dark room gonioscopy) underwent anterior segment imaging with the Visante OCT (Carl Zeiss Meditec, Dublin, CA). The anterior chamber angles at 12-o' clock hour positions were imaged and analyzed. The scleral spur at each clock hour position was independently graded by 2 observers. A scleral spur visibility score (SSVS) of 2 denotes clear visibility of the scleral spur. SSVS of 0 and 1 represent undetectable and moderately by visibile scleral spur, respectively. The interobserver agreement of the SSVS was evaluated with kappa statistics. The associations between age, sex, axial length, refraction, angle width [mean anterior chamber angle detection with edge measurement and identification algorithm (ACADEMIA) angle], and the mean SSVS were examined with univariate and multivariate analyses. The mean gonioscopy grades were 3.6 and 0.8 for the open and narrow angle groups, respectively. The interobserver agreement in grading the scleral spur visibility was 0.71. The inferior angle (6:00) had the worst visibility of the scleral spur (SSVS=1.05+/-0.49) whereas the scleral spur of the nasal angle (3:00) showed the best visibility (SSVS=1.66+/-0.46). There were significant differences between SSVS at 6:00 and the other clock hours except for 5:00 and 7:00. The mean SSVS correlated positively with gonioscopy grade, anterior chamber depth, and ACADEMIA angle, and negatively with age. The only significant factor associated with scleral spur visibility was the ACADEMIA angle (P=0.013) after adjustment for other covariates. The visibility of the scleral spur is an important determinant of the dimension of anterior chamber angle.


Reformation Capability of Short-Range Order and Their Medium-Range Connections Regulates Deformability of Bulk Metallic Glasses.
Metallic glasses (MGs) typically have high yield strength while low ductility, and the latter is commonly considered as the Achilles' heel of MGs. Elucidate the mechanism for such low ductility becomes the research focus of this field. With molecular level simulations, we show the degree of short-range order (SRO) of atomic structure for brittle Fe-based glass decreases dramatically during the stretch, while mild change occurs in ductile Zr-based glass. The reformation capability for SRO and their medium-range connections is found to be the primary characteristics to differentiate the deformability between the two metallic glasses. We suspect that, in addition to the strength of networks formed by SRO structure, the reformation capability to reform SRO networks also plays the key role in regulating the ductility in metallic glasses. Our study provides important insights into the understanding about the mechanisms accounting for ductility or brittleness of bulk metallic glasses.


Traumatic brain injury, abnormal growth hormone secretion, and gut dysbiosis.
The gut microbiome has been implicated in a variety of neuropathologies with recent data suggesting direct effects of the microbiome on host metabolism, hormonal regulation, and pathophysiology. Studies have shown that gut bacteria impact host growth, partially mediated through the growth hormone (GH)/insulin-like growth factor 1 (IGF-1) axis. However, no study to date has examined the specific role of GH on the fecal microbiome (FMB) or the changes in this relationship following a traumatic brain injury (TBI). Current literature has demonstrated that TBI can lead to either temporary or sustained abnormal GH secretion (aGHS). More recent literature has suggested that gut dysbiosis may contribute to aGHS leading to long-term sequelae now known as brain injury associated fatigue and cognition (BIAFAC). The aGHS observed in some TBI patients presents with a symptom complex including profound fatigue and cognitive dysfunction that improves significantly with exogenous recombinant human GH treatment. Notably, GH treatment is not curative as fatigue and cognitive decline typically recur upon treatment cessation, indicating the need for additional studies to address the underlying mechanistic cause.


[Conceptual analysis: methodological considerations].
Concepts are terms referring to phenomena that occur in nature or in thought, which are essential in developing research, as well as in the construction of theories. To fulfill this role in the construction of scientific knowledge, it is appropriate for them to be reviewed periodically, aiming mainly at its improvement. Despite the existence of different models of conceptual analysis, this methodology, in general, has not been well understood by nursing, especially in our reality. Therefore, in this article, of reflection, we describe some methodological considerations, including a practical approach on the methods proposed by Walker and Avant, Rodgers and Schwartz-Barcott and Kim, in order to give nurses greater understanding of this process.


Age and adverse drug reactions from psychopharmacological treatment: data from the AMSP drug surveillance programme in Switzerland.
The frequency of severe adverse drug reactions (ADRs) from psychotropic drugs was investigated in hospitalised psychiatric patients in relation to their age. Specifically, the incidence of ADRs in patients up to 60 years was compared to that of patients older than 60 years. Prescription rates of psychotropic drugs and reports of severe ADRs were collected in psychiatric hospitals in Switzerland between 2001 and 2010. The data stem from the drug surveillance programme AMSP. A total of 699 patients exhibited severe ADRs: 517 out of 28,282 patients up to 60 years (1.8%); 182 out of 11,446 elderly patients (1.6%, ns). Logistic regression analyses showed a significantly negative relationship between the incidence of ADRs and patients' age in general and in particular for weight gain, extrapyramidal motor system (EPMS) symptoms, increased liver enzymes and galactorrhoea. A significantly negative relationship was observed for age and the dosages of olanzapine, quetiapine, risperidone, valproic acid and lamotrigine. When comparing age groups, frequency of ADRs was lower in general for antipsychotic drugs and anticonvulsants, in particular for valproic acid in the elderly. Weight gain was found to be lower in the elderly for antipsychotic drugs, in particular for olanzapine. For the group of mood-stabilising anticonvulsants (carbamazepine, lamotrigine and valproic acid) the elderly exhibited a lower incidence of reported allergic skin reactions. The results suggest that for psychiatric inpatients the incidence of common severe ADRs (e.g., weight gain or EPMS symptoms) arising from psychotropic medication decreases with the age of patients.


Metagenomic Analyses of the Autotrophic Fe(II)-Oxidizing, Nitrate-Reducing Enrichment Culture KS.
Nitrate-dependent ferrous iron [Fe(II)] oxidation (NDFO) is a well-recognized chemolithotrophic pathway in anoxic sediments. The neutrophilic chemolithoautotrophic enrichment culture KS originally obtained from a freshwater sediment (K. L. Straub, M. Benz, B. Schink, and F. Widdel, Appl Environ Microbiol 62:1458-1460, 1996) has been used as a model system to study NDFO. However, the primary Fe(II) oxidizer in this culture has not been isolated, despite extensive efforts to do so. Here, we present a metagenomic analysis of this enrichment culture in order to gain insight into electron transfer pathways and the roles of different bacteria in the culture. We obtained a near-complete genome of the primary Fe(II) oxidizer, a species in the family Gallionellaceae, and draft genomes from its flanking community members. A search of the putative extracellular electron transfer pathways in these genomes led to the identification of a homolog of the MtoAB complex [a porin-multiheme cytochromec system identified in neutrophilic microaerobic Fe(II)-oxidizing Sideroxydans lithotrophicus ES-1] in a Gallionellaceae sp., and findings of other putative genes involving cytochromecand multicopper oxidases, such as Cyc2 and OmpB. Genome-enabled metabolic reconstruction revealed that this Gallionellaceae sp. lacks nitric oxide and nitrous oxide reductase genes and may partner with flanking populations capable of complete denitrification to avoid toxic metabolite accumulation, which may explain its resistance to growth in pure culture. This and other revealed interspecies interactions and metabolic interdependencies in nitrogen and carbon metabolisms may allow these organisms to cooperate effectively to achieve robust chemolithoautotrophic NDFO. Overall, the results significantly expand our knowledge of NDFO and suggest a range of genetic targets for further exploration.


Differentiation Between Malignant and Benign Endoscopic Images of Gastric Ulcers Using Deep Learning.
Endoscopic differentiation between malignant and benign gastric ulcers (GU) affects further evaluation and prognosis. The aim of our study was to evaluate a deep learning algorithm for discrimination between benign and malignant GU in a database of endoscopic ulcer images. We retrospectively collected consecutive upper gastrointestinal endoscopy images of GU performed between 2011 and 2019 at the Sheba Medical Center. All ulcers had a corresponding histopathology result of either benign peptic ulcer or gastric adenocarcinoma. A convolutional neural network (CNN) was trained to classify the images into either benign or malignant. Endoscopies from 2011 to 2017 were used for training (2011-2015) and validation (2016-2017). Hyper-parameters, image augmentation and pre-training on Google images obtained images were evaluated on the validation data. Held-out data from 2018 to 2019 was used for testing the final model. Overall, the Sheba dataset included 1978 GU images; 1894 images from benign GU and 84 images of malignant ulcers. The final CNN model showed an AUC 0.91 (95% CI 0.85-0.96) for detecting malignant ulcers. For cut-off probability 0.5, the network showed a sensitivity of 92% and specificity of 75% for malignant ulcers. Our study displays the applicability of a CNN model for automated evaluation of gastric ulcers images for malignant potential. Following further research, the algorithm may improve accuracy of differentiating benign from malignant ulcers during endoscopies and assist in patients' stratification, allowing accelerated patients management and individualized approach towards surveillance endoscopy.


Survey of local environmental health programs in Alberta.
As part of a larger initiative to develop a contemporary model for local environmental health services, a survey of Alberta health unit-based programs was undertaken. The objectives were to (a) obtain a comprehensive profile of environmental health services, and (b) identify current and emerging issues in these programs. Three survey instruments were designed for three respondent groups: chief executive officers, program managers and environmental health officers/public health inspectors. Results suggest an expanding scope of activities and issues faced by these programs. The most prevalent emerging issues noted were in the areas of chemical/ toxic exposures, injury prevention, indoor air quality and public risk perception. Issues receiving the greatest attention were food safety and waste management. Review of program management capacities suggested difficulties in coping with the increased pressures faced by these programs. Improvements recommended by respondents included increased resources, more educational and professional development opportunities, improved information systems and improved legislation.


Iatrogenic femoral neuropathy: two cases and literature update.
Iatrogenic femoral neuropathy is an uncommon surgical or obstetric complication that may be underreported. It results from compression, stretch, ischemia, or direct trauma of the nerve during hip arthroplasty, self-retaining retractor use in pelvicoabdominal surgery, lithotomy positioning for anesthesia or labor, and other more rare causes. Decreasing incidence of this complication after abdominal and gynecologic surgery but increase in its absolute numbers after hip arthroplasty has emerged over the last decade. We describe two illustrative cases related respectively to lithotomy positioning and self-retaining retractor use. The variability in clinical presentation of iatrogenic femoral nerve lesions, some new insights in their diverse pathophysiology, and in the diagnostic and treatment options are discussed with an update from the literature.


Rethinking phenotypic plasticity and its consequences for individuals, populations and species.
Much research has been devoted to identify the conditions under which selection favours flexible individuals or genotypes that are able to modify their growth, development and behaviour in response to environmental cues, to unravel the mechanisms of plasticity and to explore its influence on patterns of diversity among individuals, populations and species. The consequences of developmental plasticity and phenotypic flexibility for the performance and ecological success of populations and species have attracted a comparatively limited but currently growing interest. Here, I re-emphasize that an increased understanding of the roles of plasticity in these contexts requires a 'whole organism' (rather than 'single trait') approach, taking into consideration that organisms are integrated complex phenotypes. I further argue that plasticity and genetic polymorphism should be analysed and discussed within a common framework. I summarize predictions from theory on how phenotypic variation stemming from developmental plasticity and phenotypic flexibility may affect different aspects of population-level performance. I argue that it is important to distinguish between effects associated with greater interindividual phenotypic variation resulting from plasticity, and effects mediated by variation among individuals in the capacity to express plasticity and flexibility as such. Finally, I claim that rigorous testing of predictions requires methods that allow for quantifying and comparing whole organism plasticity, as well as the ability to experimentally manipulate the level of and capacity for developmental plasticity and phenotypic flexibility independent of genetic variation.


Reactive oxygen species are essential mediators in antigen presentation by Kupffer cells.
Kupffer cells (KC) act as APC in the liver and play a major role in the clearance of gut-derived antigens and pathogens entering the liver with portal venous blood. Antigen presentation by KC has been implicated in regulation of the local and systemic immune responses. In this study, modulation of KC antigen presentation by antioxidants and the role of reactive oxygen species (ROS) as essential mediators of antigen presentation in KC were investigated. Co-culture of KC with ovalbumin (OVA) antigens resulted in upstream intracellular endogenous ROS generation and increased expression of MHC class II and costimulator molecules, and consequent OVA-specific CD4(+) T-cell proliferation in response to antigen presentation by KC. Scavenging of KC ROS by antioxidants, or blocking of KC ROS generation by specific inhibitors of NADPH oxidase and/or xanthine oxidase, or by specific inhibitors of the mitochondrial electron transport chain, significantly decreased OVA-specific T-cell proliferation in response to antigen presentation by KC. Increased expression of MHC class II and costimulatory molecules in KC pulsed with OVA antigens was blocked by inhibiting ROS generation enzymatically. Intracellular endogenous ROS generation during antigen processing may therefore provide essential secondary signalling for KC antigen presentation.