Treatment of Hard-to-heal Diabetic Foot Ulcers With a Hepatic-derived Wound Matrix.
Difficult-to-heal diabetic foot ulcers (DFUs) increase the likelihood of significant pathology and increased health care costs. This study evaluates the ability of a novel hepatic-derived wound matrix (HD-WM) to treat hard-to-heal DFUs. In total, 53 patients were enrolled and 38 completed per protocol. Patients had ulcers that had been present for at least 90 days and were non-responsive to at least 2 applications of an advanced biologic wound care product. Patients were treated with standard of care and offloading for a 2-week run-in phase. If they satisfied criteria, they were enrolled in the trial and treated with the HD-WM, and then seen weekly for assessment and additional treatment as needed. Patients continued weekly visits until the wound healed or went 12-weeks posttreatment without healing. Mean starting wound size was 3.5 cm2 and mean wound duration was 41.1 weeks. Median previous treatment applications of an advanced biologic were 3.0. Complete closure of the wound occurred in 22 of the 38 patients (57.9%) within the 12-week study period, while 16 of 38 (42.1%) of the wounds had failed to completely heal. The mean time to wound closure was 8.1 weeks; these patients received a median of 1 application of the HD-WM under investigation. Closure of the wound by 50% or greater at week 4 was highly predictive of complete wound closure by 12 weeks. Except for bodily pain (36-Item Short Form Health Survey), which significantly improved in patients whose wounds healed, quality of life measures did not show changes. The HD-WM under evaluation did well at closing difficult-to-heal wounds with minimal applications. These results are consistent with a previous study on this HD-WM.


VtaA8 and VtaA9 from Haemophilus parasuis delay phagocytosis by alveolar macrophages.
Haemophilus parasuis, a member of the family Pasteurellaceae, is a common inhabitant of the upper respiratory tract of healthy pigs and the etiological agent of Glässer's disease. As other virulent Pasteurellaceae, H. parasuis can prevent phagocytosis, but the bacterial factors involved in this virulence mechanism are not known. In order to identify genes involved in phagocytosis resistance, we constructed a genomic library of the highly virulent reference strain Nagasaki and clones were selected by increased survival after incubation with porcine alveolar macrophages (PAM). Two clones containing two virulent-associated trimeric autotransporter (VtaA) genes, vtaA8 and vtaA9, respectively, were selected by this method. A reduction in the interaction of the two clones with the macrophages was detected by flow cytometry. Monoclonal antibodies were produced and used to demonstrate the presence of these proteins on the bacterial surface of the corresponding clone, and on the H. parasuis phagocytosis-resistant strain PC4-6P. The effect of VtaA8 and VtaA9 in the trafficking of the bacteria through the endocytic pathway was examined by fluorescence microscopy and a delay was detected in the localization of the vtaA8 and vtaA9 clones in acidic compartments. These results are compatible with a partial inhibition of the routing of the bacteria via the degradative phagosome. Finally, antibodies against a common epitope in VtaA8 and VtaA9 were opsonic and promoted phagocytosis of the phagocytosis-resistant strain PC4-6P by PAM. Taken together, these results indicate that VtaA8 and VtaA9 are surface proteins that play a role in phagocytosis resistance of H. parasuis.


The prevalence and long-term variation of hospital readmission for patients with diabetes in Tianjin, China: A cross-sectional study.
Little is known about hospital readmission for patients with diabetes in China. We aimed to assess the temporal pattern, risk factors, and variations of all-cause readmission among hospitalized patients with diabetes in Tianjin, China, from 2008 to 2013.The Tianjin Basic Medical Insurance Register System database was used to identify discharged patients with diabetes from 2008 to 2013. The influential factors and trends of rehospitalization were analyzed for 30-, 60- and 90-day predicted readmission rates. The Blinder-Oaxaca decomposition was used to explain the readmission variations between 2008 and 2013.The long stay-time at the index hospitalization is a shared risk factor for readmission at 30, 60, and 90 days each year. The 90-day predicted readmission rates were the highest for each year (all P < .001). The adjusted readmission rates generally decreased by year (all P < .001), except for at the 90-day interval, which decreased in 2010 and slightly increased in 2013 (from 7.47% in 2012 to 7.65% in 2013). If the patients had been readmitted to the hospital in 2013 and the only changes that had occurred since 2008 were observable characteristics, then the readmission rates would have decreased by 0.84%, 0.27%, and 0.18% at 30, 60, and 90 days, respectively. The potential policy changes decreased the readmission rates at 1.35%, 2.01%, and 1.04% for the 3 intervals, respectively.Identifying targeted factors for the decrease in readmission rates may help to control readmission, particularly for long-interval patients.


[Anatomic study of parapharyneal space].
The parapharyngeal space is considered the key space of the suprahioid neck, being essential to establish the origin and anatomic relations of the lesions of the profound neck. The descriptions of the fascial limits of the parapharyngeal space are variable in the litterature, reflecting some ambiguity in the manuals of anatomy and surgery. We have done a detailed study of this region, working on 5 cadavers, fixed in a solution of phenol and alcohol, and correlating the disection pieces with a radiologic study. The goal has been to improve our anatomic knowledge of the suprahioid neck, to be able to establish an anatomo-clinic-radiologic correlation of the lesions of this region, to be able to establish an differential diagnosis, predict possible ways of dissemination and facilitate the most proper surgical approach.


[Clinical study of spinal dural arteriovenous fistula-with special reference to neurological symptoms and magnetic resonance imaging].
We have evaluated the backgrounds, neurological symptoms, signs, and magnetic resonance images (MRI) in six cases of spinal dural arteriovenous fistula. The subjects were 2 males and 4 females, and the mean age was 67.2 years old. The cardinal subjective symptoms were progressive motor weakness of lower extremities (2 cases), paroxyomal weakness of lower extremities (3 cases), sensory disturbance of polyneuritic type (2 cases), and intermittent claudication (1 case). Administration of beverages and drugs, which might include vasodilators and taking baths, worsened the symptoms and signs in 3 cases and 2 cases respectively. Concerning to MRI findings, high signal intensities or swellings were observed at mid-thoracic area to upper conus of the spinal cord in all cases. These changes, which would be induced by edema caused by high venous pressure, were especially prominent in the central area of the cords. By these mechanisms, sensory disturbance like polyneuritic type caused by the disturbance in deep areas of posterior columns might more prominent than the disorder of spinothalamic tracts placed in superficial areas of cord in the early stage of the disease. These abnormal intensities of MRI were higher than the level of clinical symptoms and signs. The difference was about 6.5 segments. For this reason, the upper border of the spinal cord lesions could not be identified by the neurological symptoms. Although the clinical features and MRI findings are relatively characteristic, flow void signs by high resonance MRI and abnormal blood vessels by spinal angiography will be necessary to diagnose this disease confidently.


Ornithine cyclodeaminase-based proline production by Corynebacterium glutamicum.
The soil bacterium Corynebacterium glutamicum, best known for its glutamate producing ability, is suitable as a producer of a variety of bioproducts. Glutamate is the precursor of the amino acid proline. Proline biosynthesis typically involves three enzymes and a spontaneous cyclisation reaction. Alternatively, proline can be synthesised from ornithine, an intermediate of arginine biosynthesis. The direct conversion of ornithine to proline is catalysed by ornithine cyclodeaminase. An ornithine overproducing platform strain with deletions of argR and argF (ORN1) has been employed for production of derived compounds such as putrescine. By heterologous expression of ocd this platform strain can be engineered further for proline production. Plasmid-based expression of ocd encoding the putative ornithine cyclodeaminase of C. glutamicum did not result in detectable proline accumulation in the culture medium. However, plasmid-based expression of ocd from Pseudomonas putida resulted in proline production with yields up to 0.31 ± 0.01 g proline/g glucose. Overexpression of the gene encoding a feedback-alleviated N-acetylglutamate kinase further increased proline production to 0.36 ± 0.01 g/g. In addition, feedback-alleviation of N-acetylglutamate kinase entailed growth-coupled production of proline and reduced the accumulation of by-products in the culture medium. The product spectrum of the platform strain C. glutamicum ORN1 was expanded to include the amino acid L-proline. Upon further development of the ornithine overproducing platform strain, industrial production of amino acids of the glutamate family and derived bioproducts such as diamines might become within reach.


A Systematic Review of Resistance Training Versus Endurance Training in COPD.
Endurance training (ET) as part of pulmonary rehabilitation in patients with chronic obstructive pulmonary disease (COPD) has been shown to improve exercise capacity and health-related quality of life, but dyspnea limits the exercise intensity. Therefore, resistance training (RT), which may cause less dyspnea, could be an alternative. The purpose of this review was to formulate evidence-based recommendations on the use of RT in pulmonary rehabilitation of patients with COPD. Our primary outcomes were health-related quality of life, activities of daily living, dyspnea, possible harm, and total mortality. Our secondary outcomes were walking distance, lean body mass, muscle strength, and exercise capacity. We identified randomized controlled trials through a systematic multidatabase search. One author checked titles and abstracts for relevance using broad inclusion criteria, whereas 2 authors independently checked the full-text articles for eligibility. Two authors independently extracted data and assessed the risk of bias and quality of evidence. Meta-analyses were performed when deemed feasible based on the quality and amount of data. We included 8 randomized controlled trials (328 participants). On the basis of moderate- to very low-quality evidence, we found no clinically important difference between RT and ET. We did not find sufficient data for a meta-analysis of total mortality, adverse events, dyspnea, or lean body mass. We found that in patients with COPD, RT seems to induce the same beneficial effects as ET. Therefore, we recommend that RT should be considered according to patient preferences when designing a pulmonary rehabilitation program for patients with COPD.


Plasma Proteomics Enable Differentiation of Lung Adenocarcinoma from Chronic Obstructive Pulmonary Disease (COPD).
Chronic obstructive pulmonary disease (COPD) is a major risk factor for the development of lung adenocarcinoma (AC). AC often develops on underlying COPD; thus, the differentiation of both entities by biomarker is challenging. Although survival of AC patients strongly depends on early diagnosis, a biomarker panel for AC detection and differentiation from COPD is still missing. Plasma samples from 176 patients with AC with or without underlying COPD, COPD patients, and hospital controls were analyzed using mass-spectrometry-based proteomics. We performed univariate statistics and additionally evaluated machine learning algorithms regarding the differentiation of AC vs. COPD and AC with COPD vs. COPD. Univariate statistics revealed significantly regulated proteins that were significantly regulated between the patient groups. Furthermore, random forest classification yielded the best performance for differentiation of AC vs. COPD (area under the curve (AUC) 0.935) and AC with COPD vs. COPD (AUC 0.916). The most influential proteins were identified by permutation feature importance and compared to those identified by univariate testing. We demonstrate the great potential of machine learning for differentiation of highly similar disease entities and present a panel of biomarker candidates that should be considered for the development of a future biomarker panel.


Exploring how nurse managers' knowledge of succession planning affects their leadership and organisational resilience.
The effectiveness and stability of a healthcare organisation's workforce, including nurse managers, can be negatively affected by many factors, including illness, retirement and low levels of retention. One way of mitigating these effects is through succession planning, which can be defined as a strategy to employ the appropriate number and quality of people in key positions such as management to account for factors such as turnover, which can cause instability in a workforce. Many healthcare organisations understand the importance of having trained individuals who are ready to be promoted into leadership and managerial roles vacated by those who leave or are promoted into other positions. However, few formal education programmes specifically target the leadership development of nurses and their potential to progress into more complex leadership positions. To assess the effect of nurse managers' knowledge of succession planning on leadership practices and organisational resilience. A quasi-experimental research design was applied using a test conducted before and after sessions on knowledge of succession planning, with a group of 60 nurse managers working at a Saudi university hospital. Each nurse manager attended the sessions. Study variables were measured using structured questionnaires before and after attendance. The results showed significant improvement after the sessions. Improvements were noted in knowledge of succession planning, leadership and succession planning practices, and organisational resilience. This study demonstrated that providing sessions on succession planning resulted in improvements in nurse managers' knowledge of succession planning, demonstration of succession planning practices, and demonstration of leadership practices.


Isolated vaginal recurrence in women with stage I endometrial cancer.
To compare clinical and pathologic characteristics of women with surgical stage I endometrial carcinoma by location of first recurrence and describe characteristics of isolated vaginal recurrence. Patients with 2009 International Federation of Obstetrics and Gynecology (FIGO) stage I endometrial carcinoma treated at two large cancer centers from 1/1/2009-12/31/2017 were identified. Sarcoma histology was excluded. Recurrences were grouped into isolated vaginal or extravaginal. Isolated vaginal recurrences were localized by anatomic location within the vaginal vault. Clinical and pathologic variables were compared with chi-square analysis, and Kaplan-Meier curves with log-rank tests. Of 2815 women identified, 278 (10%) experienced a recurrence. Sixty-one patients (2%) had an isolated vaginal recurrence, including 42 (69%) at the vaginal apex; 217 (8%) had an extravaginal recurrence, including 18 with a vaginal component. Median time to recurrence was 11 months (range, 1-68) for isolated vaginal recurrence and 20 months (range, 1-98) for extravaginal recurrence (P < .004). Of 960 patients (34%) treated with adjuvant vaginal brachytherapy (VBT), 156 (16%) recurred; 19 (2%) had an isolated vaginal recurrence, including 16 (84%) at the vaginal apex. Three-year PFS rates for isolated vaginal recurrence were 97.6% (SE ± 0.4%) with minimally invasive surgery (MIS) versus 96.9% (SE ± 1.1%) with open (P = .8), and for extravaginal recurrence were 91.8% (SE ± 0.7%) with MIS versus 90.8% (SE ± 1.8%) with open (P = .8). Isolated vaginal recurrences in stage I endometrial cancer are detected earlier than non-vaginal recurrences. Surgical approach does not appear to impact recurrence. Adjuvant VBT after primary surgery carries a 1%-2% risk of isolated vaginal apex recurrence.


Guidelines for the genetic diagnosis of hereditary recurrent fevers.
Hereditary recurrent fevers (HRFs) are a group of monogenic autoinflammatory diseases characterised by recurrent bouts of fever and serosal inflammation that are caused by pathogenic variants in genes important for the regulation of innate immunity. Discovery of the molecular defects responsible for these diseases has initiated genetic diagnostics in many countries around the world, including the Middle East, Europe, USA, Japan and Australia. However, diverse testing methods and reporting practices are employed and there is a clear need for consensus guidelines for HRF genetic testing. Draft guidelines were prepared based on current practice deduced from previous HRF external quality assurance schemes and data from the literature. The draft document was disseminated through the European Molecular Genetics Quality Network for broader consultation and amendment. A workshop was held in Bruges (Belgium) on 18 and 19 September 2011 to ratify the draft and obtain a final consensus document. An agreed set of best practice guidelines was proposed for genetic diagnostic testing of HRFs, for reporting the genetic results and for defining their clinical significance.


TNF-induced death signaling triggers alveolar epithelial dysfunction in acute lung injury.
The ability of the alveolar epithelium to prevent and resolve pulmonary edema is a crucial determinant of morbidity and mortality in acute lung injury (ALI). TNF has been implicated in ALI pathogenesis, but the precise mechanisms remain undetermined. We evaluated the role of TNF signaling in pulmonary edema formation in a clinically relevant mouse model of ALI induced by acid aspiration and investigated the effects of TNF p55 receptor deletion, caspase-8 inhibition, and alveolar macrophage depletion on alveolar epithelial function. We found that TNF plays a central role in the development of pulmonary edema in ALI through activation of p55-mediated death signaling, rather than through previously well-characterized p55-mediated proinflammatory signaling. Acid aspiration produced pulmonary edema with significant alveolar epithelial dysfunction, as determined by alveolar fluid clearance (AFC) and intra-alveolar levels of the receptor for advanced glycation end-products. The impairment of AFC was strongly correlated with lung caspase-8 activation, which was localized to type 1 alveolar epithelial cells by flow cytometric analysis. p55-deficient mice displayed markedly attenuated injury, with improved AFC and reduced caspase-8 activity but no differences in downstream cytokine/chemokine production and neutrophil recruitment. Caspase-8 inhibition significantly improved AFC and oxygenation, whereas depletion of alveolar macrophages attenuated epithelial dysfunction with reduced TNF production and caspase-8 activity. These results provide in vivo evidence for a novel role for TNF p55 receptor-mediated caspase-8 signaling, without substantial apoptotic cell death, in triggering alveolar epithelial dysfunction and determining the early pathophysiology of ALI. Blockade of TNF-induced death signaling may provide an effective early-phase strategy for ALI.


Childrens' learning and behaviour and the association with cheek cell polyunsaturated fatty acid levels.
Increasing interest in the role of omega-3 fatty acids in relation to neurodevelopmental disorders (e.g. ADHD, dyslexia, autism) has occurred as a consequence of some international studies highlighting this link. In particular, some studies have shown that children with ADHD may have lower concentrations of polyunsaturated fatty acids (PUFAs), particularly omega-3, in their red blood cells and plasma, and that supplementation with omega-3 fatty acids may alleviate behavioural symptoms in this population. However, in order to compare levels it seems appropriate to establish fatty acid levels in a mainstream school aged population and if levels relate to learning and behaviour. To date no study has established this. For this study, cheek cell samples from 411 typically developing school children were collected and analysed for PUFA content, in order to establish the range in this population. In addition, measures of general classroom attention and behaviour were assessed in these children by teachers and parents. Cognitive performance tests were also administered in order to explore whether an association between behaviour and/or cognitive performance and PUFA levels exists. Relationships between PUFA levels and socio-economic status were also explored. Measures of reading, spelling and intelligence did not show any association with PUFA levels, but some associations were noted with the level of omega-3 fatty acids and teacher and parental reports of behaviour, with some evidence that higher omega-3 levels were associated with decreased levels of inattention, hyperactivity, emotional and conduct difficulties and increased levels of prosocial behaviour. These findings are discussed in relation to previous findings from omega-3 supplementation studies with children.


Nonlinear optical properties of spirocyclohexadine photochromes: insights from DFT calculations.
The second-order nonlinear optical properties of 1,3-indandione-derived spirocyclohexadine compounds, a new class of photochromes showing sensitivity to both UV and visible lights, are investigated by means of density functional theory. The calculations predict that these compounds should display a large first hyperpolarizability variation upon commutation between their cyclic spiropyran and their merocyanine form. We also show that significant enhancement of the NLO response of the merocyanine form, as well as of the NLO contrast, can be achieved by means of appropriate chemical substitution, which makes these derivatives highly appealing for potential use in photo-responsive NLO devices.


Results of Intraoperative Sodium Fluorescein Video Angiography and Its Repeated Use in a Series of Brain Aneurysm Surgeries.
To present the properities of intraoperative sodium fluorescein video angiography (NaF-V) use in intracranial aneurysm surgery and to discuss the limitations of repeated NaF-V administration. The clinical findings and imaging results during and after surgery for patients with aneurysm who underwent surgery between September 2020 and June 2022 were examined. NaF-V and micro-doppler imaging were used to control the flow of the parent and perforating arteries and obliteration of the aneurysm dome. The dose of sodium fluorescein administered via the central venous route was 5 mg/kg. Overall, 102 aneurysms were treated during 95 operations in 92 patients. NaF-V was applied at least once in all operations, twice in 17, and thrice in 3 operations. The period between repeated doses of NaF-V ranged from 4 to 50 min. The method allowed for the desired imaging of the parent and perforating arteries in all cases but failed to provide satisfactory results regarding the complete obliteration of the aneurysm dome in three cases. No NaF-V-related complications were encountered in any case. Sodium fluorescein is safe, with a high minimum toxic dosage, and provides benefits, even in repeated use, in the evaluation of perforating and parent arteries. NaF-V is effective when used alternatively or in combination with various methods.


Model for ASsessing the value of Artificial Intelligence in medical imaging (MAS-AI).
Artificial intelligence (AI) is seen as a major disrupting force in the future healthcare system. However, the assessment of the value of AI technologies is still unclear. Therefore, a multidisciplinary group of experts and patients developed a Model for ASsessing the value of AI (MAS-AI) in medical imaging. Medical imaging is chosen due to the maturity of AI in this area, ensuring a robust evidence-based model. MAS-AI was developed in three phases. First, a literature review of existing guides, evaluations, and assessments of the value of AI in the field of medical imaging. Next, we interviewed leading researchers in AI in Denmark. The third phase consisted of two workshops where decision makers, patient organizations, and researchers discussed crucial topics for evaluating AI. The multidisciplinary team revised the model between workshops according to comments. The MAS-AI guideline consists of two steps covering nine domains and five process factors supporting the assessment. Step 1 contains a description of patients, how the AI model was developed, and initial ethical and legal considerations. In step 2, a multidisciplinary assessment of outcomes of the AI application is done for the five remaining domains: safety, clinical aspects, economics, organizational aspects, and patient aspects. We have developed an health technology assessment-based framework to support the introduction of AI technologies into healthcare in medical imaging. It is essential to ensure informed and valid decisions regarding the adoption of AI with a structured process and tool. MAS-AI can help support decision making and provide greater transparency for all parties.


[Late-onset neonatal sepsis in preterm infants with birth weight under 1.500 g].
The research objective was to characterize preterm infants with birth weight under 1500 g, and to identify the incidence of late-onset neonatal sepsis among this population. A prospective cohort study with a sample of 30 preterm newborns that weighed under 1500 g and were hospitalized in the NICU of the university hospital. Data were collected from January to December 2013 using a structured instrument. Of the 30 neonates included in the study, 14 developed late-onset neonatal sepsis with a prevalence of coagulase-negative staphylococci. The incidence of late-onset neonatal sepsis indicates a vulnerability in preterm infants due to immunological immaturity. These results reveal that knowledge of the profile of newborn infants admitted to the NICU and the risk factors to which they are exposed are central to the planning of nursing care for these patients. Future studies should address strategies for preventing nosocomial infection.


Protective effect of thymoquinone against diazinon-induced hematotoxicity, genotoxicity and immunotoxicity in rats.
Several studies have shown that oxidative stress and cell damage can occur in the very early stages of diazinon (DZN) exposure. The present study was designed to determine the beneficial effect of thymoquinone (Thy), the main component of Nigella sativa (black seed or black cumin) against DZN immunotoxicity, hematotoxicity and genotoxicity in rats. In the present experimental study, 48 male Wistar rats were randomly divided into six groups, (eight per group) as follows: control (receiving corn oil as the DZN solvent), DZN (20mg/kg), Thy (10mg/kg), Thy (2.5mg/kg)+DZN, Thy (5mg/kg)+DZN and Thy (10mg/kg)+DZN. After four weeks of treatment, the hematological parameters of red blood cells (RBCs), white blood cells (WBCs), hemoglobin (Hb), hematocrit (Hct) and platelets (PLTs) were evaluated. The evaluation of genotoxicity was carried out using the micronucleus assay. For measurement of cytokine production, interferon gamma (IFN-γ), interleukin 10 (IL10) and interleukin 4 (IL4) were chosen as immunotoxicity indicators of DZN toxicity. DZN was found to decrease RBCs, WBCs, Hb, Hct, PLTs, butyrl- and acetyl-cholinesterase activity and I FN-γ and increased the micronucleus indices of IL10 and IL4 as compared with the control group. Treatment with Thy reduced DZN hematotoxicity and immunotoxicity, but, significantly, did not prevent genotoxicity. This study showed that Thy (without the significant effect on genotoxicity) decreased the hematological toxicity, immunotoxicity and butyrl and acetyl cholinesterase activity induced by DZN. The success of Thy supplementation against DZN toxicity can be attributed to the antioxidant effects of its constituents.


The Annual American Men's Internet Survey of Behaviors of Men Who Have Sex With Men in the United States: Key Indicators Report 2018.
The American Men's Internet Survey (AMIS) is an annual web-based behavioral survey conducted in the United States of men who have sex with men (MSM). This rapid surveillance report describes the sixth cycle of data collection (September-December 2018; AMIS 2018). The key indicators were the same as those previously reported for past AMIS cycles. The AMIS methodology has not substantively changed since AMIS 2017. MSM were recruited from a variety of websites using banner advertisements and email blasts. In addition, participants from AMIS 2017 who agreed to be recontacted for future research were emailed a link to AMIS 2018. Men were eligible to participate if they were aged ≥15 years, resided in the United States, provided a valid US ZIP code, and reported ever having sex with a man or identified as gay or bisexual. The analysis was limited to those who reported having oral or anal sex with a male partner in the past 12 months. We examined demographic and recruitment characteristics using multivariable regression modeling (P<.05) stratified by the participants' self-reported HIV status. The AMIS 2018 round of data collection resulted in 10,129 completed surveys from MSM representing every US state, Puerto Rico, and Guam. Most participants were non-Hispanic White, aged between 15 and 24 years, living in urban areas in the southern United States, and recruited from general social networking websites. The plurality (4230/10,129, 41.76%) of participants was in the youngest age group, 15-24 years, followed by the 40 years and older age group (3088/10,129, 30.49%). The self-reported HIV prevalence was 6.08% (616/10,129). Compared with HIV-negative or unknown status participants, HIV-positive participants were more likely to have had anal sex without a condom with a male partner in the past 12 months (adjusted odds ratio [aOR] 2.02, 95% CI 1.63-2.50) and more likely to have had anal sex without a condom with a serodiscordant or an unknown status partner (aOR 3.90, 95% CI 3.27-4.66). The reported use of marijuana in the past 12 months was higher among HIV-positive participants than among HIV-negative or unknown status participants (aOR 1.39, 95% CI 1.15-1.68). The reported use of methamphetamines and other illicit substances in the past 12 months was higher among HIV-positive participants than among HIV-negative or unknown status participants (aOR 3.42, 95% CI 2.41-4.87 and aOR 1.90, 95% CI 1.56-2.32, respectively). Most HIV-negative or unknown status participants (6838/9513, 71.88%) reported ever taking an HIV test previously, and 52.51% (4995/9513) of the participants reported undergoing HIV testing in the past 12 months. HIV-positive participants were more likely to report testing and diagnosis of sexually transmitted infections than HIV-negative or unknown status participants (aOR 3.50, 95% CI 2.89-4.24 and aOR 2.61, 95% CI 2.10-3.25, respectively).


Diverse Mesorhizobium plurifarium populations native to Mexican soils.
Forty-six Mesorhizobium strains associated with the leguminous plants Leucaena leucocephala and Sesbania herbacea in an uncultivated Mexican field were characterized using a polyphasic approach. The strains were identified as Mesorhizobium plurifarium based upon the close relationships with the reference strains for this species in PCR-based restriction fragment length polymorphism analyses, sequencing of 16S rRNA genes, multilocus enzyme electrophoresis, and DNA-DNA hybridization. Although the strains isolated from both plants formed the same group in multilocus enzyme electrophoresis and cross-nodulations were observed in the laboratory, different electrophoretic types were obtained from the two plants grown in natural soils, indicating the existence of a preferable association between the plants and the rhizobia. The M. plurifarium strains from Mexico and the reference strains from Africa and Brazil formed different phenotypic clusters in a numerical taxonomy. The Mexican strains did not grow at 37 degrees C and were sensitive to salty-alkaline conditions, while the reference strains from Africa and Brazil grew at 42 degrees C and were more resistant to salty-alkaline conditions. These results demonstrate that both the plants and environmental factors affected the evolution of rhizobia and that the Mexican strains had adapted to the neutral soils and the cool climate where they were isolated.


The Cx43 Carboxyl-Terminal Mimetic Peptide αCT1 Protects Endothelial Barrier Function in a ZO1 Binding-Competent Manner.
The Cx43 carboxyl-terminus (CT) mimetic peptide, αCT1, originally designed to bind to Zonula Occludens 1 (ZO1) and thereby inhibit Cx43/ZO1 interaction, was used as a tool to probe the role of Cx43/ZO1 association in regulation of epithelial/endothelial barrier function. Using both in vitro and ex vivo methods of barrier function measurement, including Electric Cell-Substrate Impedance Sensing (ECIS), a TRITC-dextran Transwell permeability assay, and a FITC-dextran cardiovascular leakage protocol involving Langendorff-perfused mouse hearts, αCT1 was found to protect the endothelium from thrombin-induced breakdown in cell-cell contacts. Barrier protection was accompanied by significant remodeling of the F-actin cytoskeleton, characterized by a redistribution of F-actin away from the cytoplasmic and nuclear regions of the cell, towards the endothelial cell periphery, in association with alterations in cellular chiral orientation distribution. In line with observations of increased cortical F-actin, αCT1 upregulated cell-cell border localization of endothelial VE-cadherin, the tight junction protein Zonula Occludens 1 (ZO1), and the Gap Junction Protein (GJ) Connexin43 (Cx43). A ZO1 binding-incompetent variant of αCT1, αCT1-I, indicated that these effects on barrier function and barrier-associated proteins, were likely associated with Cx43 CT sequences retaining ability to interact with ZO1. These results implicate the Cx43 CT and its interaction with ZO1, in the regulation of endothelial barrier function, while revealing the therapeutic potential of αCT1 in the treatment of vascular edema.


Gonadal steroid attenuation of developing hamster facial motoneuron loss by axotomy: equal efficacy of testosterone, dihydrotestosterone, and 17-beta estradiol.
In the hamster facial nerve injury paradigm, we have established that androgens enhance both functional recovery from facial nerve paralysis and the rate of regeneration in the adult, through intrinsic effects on the nerve cell body response to injury and via an androgen receptor (AR)-mediated mechanism. Whether these therapeutic effects of gonadal steroids encompass neuroprotection from axotomy-induced cell death is the focus of the present study. Virtually 100% of adult hamster facial motoneurons (FMNs) survive axotomy at the stylomastoid foramen (SMF), whereas, before postnatal day 15 (P15), developing FMNs undergo substantial axotomy-induced cell death. The first part of the present study focuses on determining when ARs are first expressed in developing hamster FMNs. Using AR immunocytochemistry, it was found that males express ARs by P2 and females by P4, which is the earliest demonstration of AR expression in mammalian motoneurons reported thus far in the literature. The second half examines the neuroprotective effects of testosterone propionate, 17-beta estradiol, and dihydrotestosterone on FMNs of P7 hamsters after facial nerve transection at the SMF. The results demonstrate that androgens and estrogens are equally able to rescue approximately 20% of FMNs from axotomy-induced cell death, with the effects permanent. This study is the first to investigate the effects of both androgens and estrogens on axotomy-induced cell death in one system and, with our previously published work, to validate the hamster FMN injury paradigm as a model of choice in the investigation of both neurotherapeutic and neuroprotective actions of gonadal steroids.


Unusual eustachian tube mass: glomus tympanicum.
A case of recurrent glomus tympanicum presenting with epistaxis is described. CT and MR imaging revealed a homogeneously enhancing mass extending along the entire course of the eustachian tube, with a portion protruding into the nasopharynx. Glomus tumors tend to spread along the path of least resistance and may extend into the eustachian tube. The unique imaging appearance should place a glomus tumor high on the list of differential diagnoses.


Pulse-shape dependence of stimulated Brillouin scattering pulse compression to sub-phonon lifetime.
A new approach to sub-phonon lifetime pulse compression by stimulated Brillouin scattering (SBS) is presented. Triangular and step pulse pumps are both used as a pump source in a single-cell SBS compression setup. Compared with a Gaussian pump (shortest compressed pulse is the phonon lifetime with the highest energy conversion, approximately 60% under the same conditions), the compression ratio is significantly improved in the case of triangular and step pulse pumps, and there is some improvement in the energy conversion when a step pulse pump is used. A pulse as short as a quarter of a phonon lifetime is produced by a triangular pulse pump, with an energy conversion above 30%. The pump pulse shape is identified as the key parameter in achieving sub-phonon lifetime pulse compression. By using a step pulse shape, a 4.5 ns pump pulses with a 60mJ at 1064-nm are compressed down to 292 ps (below semi-phonon-lifetime) in 3M Fluorinert Electronic Liquid FC-770 with an energy conversion above 65%. This work presents a route to reliable generation of sub-semi-phonon-lifetime pulses by SBS compression.


An improved high-throughput lipid extraction method for the analysis of human brain lipids.
We have developed a protocol suitable for high-throughput lipidomic analysis of human brain samples. The traditional Folch extraction (using chloroform and glass-glass homogenization) was compared to a high-throughput method combining methyl-tert-butyl ether (MTBE) extraction with mechanical homogenization utilizing ceramic beads. This high-throughput method significantly reduced sample handling time and increased efficiency compared to glass-glass homogenizing. Furthermore, replacing chloroform with MTBE is safer (less carcinogenic/toxic), with lipids dissolving in the upper phase, allowing for easier pipetting and the potential for automation (i.e., robotics). Both methods were applied to the analysis of human occipital cortex. Lipid species (including ceramides, sphingomyelins, choline glycerophospholipids, ethanolamine glycerophospholipids and phosphatidylserines) were analyzed via electrospray ionization mass spectrometry and sterol species were analyzed using gas chromatography mass spectrometry. No differences in lipid species composition were evident when the lipid extraction protocols were compared, indicating that MTBE extraction with mechanical bead homogenization provides an improved method for the lipidomic profiling of human brain tissue.


Proline-induced inhibition of glutamate release in hippocampal area CA1.
Concentrations of proline typical of human CSF have been shown to potentiate transmission at Schaffer collateral-commissural synapses on CA1 pyramidal cells of the rat hippocampus. This study tested the hypothesis that proline enhances excitatory synaptic transmission by increasing glutamate release. Two concentrations of proline were used: a concentration typical of normal human CSF (3 microM) and a concentration typical of CSF in persons with the genetic disorder hyperprolinemia type II (30 microM). Continuous exposure of hippocampal slices to either concentration of proline potentiated Schaffer collateral-commissural synaptic transmission. Proline shifted the plot of field EPSP slope against fiber volley amplitude upward. Contrary to the original hypothesis, neither concentration of proline reduced paired-pulse facilitation; 30 microM proline enhanced paired-pulse facilitation, whereas 3 microM proline had no effect. In line with its enhancement of paired-pulse facilitation, 30 microM proline reduced both the K+-evoked release of glutamate and aspartate from CA1 slices and the release of glutamate and aspartate from CA1 synaptosomes evoked by 4-aminopyridine. These results suggest that the proline-induced potentiation of Schaffer collateral-commissural synaptic transmission probably involves a postsynaptic, rather than a presynaptic, mechanism. Concentrations of proline normally found in human CSF little affect glutamate release. However, proline-induced inhibition of glutamate release may contribute to the neuropsychiatric disorders associated with hyperprolinemia type II.


Hormonal responses to the 6-minute walk test in women and men with coronary heart disease: a pilot study.
Women with coronary heart disease (CHD) are more likely than men to develop congestive heart failure (CHF). Dysregulation of sympathetic and volume-regulatory hormones may contribute to the onset of symptomatic CHF. We hypothesized that this hormonal dysregulation develops at an earlier stage of CHD in women than in men. The study goals were (1) to determine the effect of gender on basal and exercise-induced plasma concentrations of catecholamines and volume-regulatory hormones in patients diagnosed with CHD, New York Heart Association class I and (2) to determine efficacy of the 6-minute walk test as a stimulus for release of these hormones. Study participants were 9 women and 9 men with normal left ventricular ejection fraction (>50%) and CHD confirmed by arteriography. Data were collected under resting conditions, and after the 6-minute walk test, in the general clinical research center of a northeastern university medical center. Basal plasma vasopressin (VP) concentration was significantly higher in men than in women (P = .018). Exercise, for women and men combined, significantly increased atrial natriuretic peptide (P < .0005), VP (P = .04), norepinephrine (P < .0005), and epinephrine (P = .038) but not plasma renin activity (P = .09). No further gender differences were detected for basal levels, or for the magnitude of exercise-induced increases, for any of the hormones measured. The 6-minute walk test is an exercise of sufficient intensity and duration to initiate the release of hormones associated with sympathetic activation and fluid-electrolyte regulation in both women and men with CHD. It appears that a gender difference was detected only for basal VP levels.


The 117 call alert system in Sierra Leone: from rapid Ebola notification to routine death reporting.
A toll-free, nationwide phone alert system was established for rapid notification and response during the 2014-2015 Ebola epidemic in Sierra Leone. The system remained in place after the end of the epidemic under a policy of mandatory reporting and Ebola testing for all deaths, and, from June 2016, testing only in case of suspected Ebola. We describe the design, implementation and changes in the system; analyse calling trends during and after the Ebola epidemic; and discuss strengths and limitations of the system and its potential role in efforts to improve death reporting in Sierra Leone. Numbers of calls to report deaths of any cause (death alerts) and persons suspected of having Ebola (live alerts) were analysed by province and district and compared with numbers of Ebola cases reported by the WHO. Nearly 350 000 complete, non-prank calls were made to 117 between September 2014 and December 2016. The maximum number of daily death and live alerts was 9344 (October 2014) and 3031 (December 2014), respectively. Call volumes decreased as Ebola incidence declined and continued to decrease in the post-Ebola period. A national social mobilisation strategy was especially targeted to influential religious leaders, traditional healers and women's groups. The existing infrastructure and experience with the system offer an opportunity to consider long-term use as a death reporting tool for civil registration and mortality surveillance, including rapid detection and control of public health threats. A routine social mobilisation component should be considered to increase usage.


Lipid-lowering and antioxidant effects of an ethyl acetate extract of fenugreek seeds in high-cholesterol-fed rats.
The purpose of this study was to investigate the relationship between the lipid effects, the phenolic content, and the antioxidative effects of an ethyl acetate extract of fenugreek. Wistar rats fed a standard laboratory diet or cholesterol-rich diets for 16 weeks were used. The plasma lipid levels, total phenolics, and total flavonoid contents were measured, and the thiobarbituric acid reactive substances (TBARS) and antioxidant activities were examined. Administration of fenugreek ethyl acetate extract significantly lowered the plasma levels of total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C), while increasing the plasma level of high-density lipoprotein cholesterol (HDL-C). Furthermore, the content of TBARS and catalase (CAT) and superoxide dismutase (SOD) activities in liver, heart and kidney decreased significantly after oral administration of the extract compared with those of rats fed a cholesterol-rich diet. These lipid effects and in vivo antioxidative effects were correlated with the in vitro phenolic content scavenging ability. In addition, three flavonoids (kaempferol 3-O-glycoside, apigenin-7-O-rutinoside, and naringenin) were identified by using an LC-MS/MS apparatus. Naringenin was the abundant flavonoid compound in the ethyl acetate extract, and its concentration reaches 7.23 +/- 0.09 mg/g of dry extract. These results revealed significant hypocholesterolemic effects and antioxidant activity in an ethyl acetate extract of fenugreek seed, which may be partly due to the presence of flavonoids, especially naringenin.


The Usage of OHDSI OMOP - A Scoping Review.
OHDSI, a fast growing open-science research community seeks to enable researchers from around the globe to conduct network studies based on standardized data and vocabularies. There is no comprehensive review of publications about OHDSI's standard: the OMOP Common Data Model and its usage available. In this work we aim to close this gap and provide a summary of existing publications including the analysis of its meta information such as the choice of journals, journal types, countries, as well as an analysis by topics based on a title and abstract screening. Since 2016, the number of publications has been constantly growing and the relevance of the OMOP CDM is increasing in terms of multi-country studies based on observational patient data.


TGF-β-MTA1-SMAD7-SMAD3-SOX4-EZH2 Signaling Axis Promotes Viability, Migration, Invasion and EMT of Hepatocellular Carcinoma Cells.
Enhancer of zeste homolog 2 (EZH2) is implicated in hepatocellular carcinoma (HCC), but whether transforming growth factor-β (TGF-β)-metastasis associated 1 (MTA1)-SMAD7-SMAD3-SRY-Box Transcription Factor 4 (SOX4)-EZH2 signaling axis, in which EZH2 participates, is also involved in HCC remained unknown. Data on EZH2 expression in liver hepatocellular carcinoma (LIHC) and its relation with prognosis of HCC patients were predicted and analyzed using online databases. Following transfection with or without TGF-β1, HCC cell viability, migration and invasion were determined with MTT, Scratch and Transwell assays. Relative expressions of epithelial-to-mesenchymal transition (EMT)-related factors (N-Cadherin, Vimentin, and E-Cadherin) and TGF-β-MTA1-SMAD7-SMAD3-SOX4-EZH2 signaling axis factors (TGF-β, MTA1, SMAD7, phosphorylated-SMAD3, SOX4 and EZH2) were calculated via reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot. EZH2 was upregulated in HCC, which was related to poor prognosis. Silencing EZH2 suppressed EZH2 expression and HCC cell viability, migration, and invasion, and increased E-Cadherin expression yet decreased N-Cadherin and Vimentin expression, whereas EZH2 overexpression did conversely. Also, silencing EZH2 reversed the effects of TGF-β1 on promoting viability, migration, and invasion, as well as N-Cadherin and Vimentin expressions, yet suppressing E-Cadherin expression in HCC cells. In addition, TGF-β1 promoted TGF-β, MTA1, SOX4 and EZH2 expressions and p-SMAD3/SMAD3 ratio yet suppressed SMAD7, whereas silencing EZH2 solely reversed the effects of TGF-β1 on EZH2 expression in HCC cells. The present study provides a theoretical basis for TGF-β-MTA1-SMAD7-SMAD3-SOX4-EZH2 signaling cascade in viability, migration, invasion, and EMT of HCC cells. Inhibiting these signals may represent a therapeutic pathway for the treatment of metastatic HCC.


Underserved populations and bacterial and protozoal sexually transmitted infections: a lost health-care opportunity.
The purpose of our review is an update about the burden of sexually transmitted infections (STIs) among various types of underserved populations, such as migrants, substance abusers, homeless and incarcerated inmates. First-line test and treatment based on the latest available evidence according to the revised guidelines of Centers for Disease Control and Prevention have also been considered. We performed a comprehensive research using scientific databases such as Medline and Pubmed, followed by a review of citations and reference list. A consultation with other experts in the management of the various subpopulations was also conducted. Health-care is often influenced by social determinants, which play a vital role in the diffusion of STIs. The consequence is a socio-economical and ethnic disparity in the rate of STIs. Early screening and treatment of STIs should be implemented in clinical practice, starting from marginalized social groups, which are the most affected by this health problem. In the literature, there are very few papers containing information on STIs prevalence in various types of underserved populations, such as migrants, substance abusers, homeless and incarcerated inmates. The availability of more accurate epidemiological data is needed. In these groups, the most relevant barrier is the lower perception of health-care need, with an underestimation of risk and symptoms of STIs, causing a retard of diagnosis and health-care provision and use. For these populations, targeted interventions are needed, particularly on unaware people, responsible for most STIs transmissions.


Coimmobilization of gluconolactonase with glucose oxidase for improvement in kinetic property of enzymatically induced volume collapse in ionic gels.
The object of this paper is to provide an enzymatic means to attain faster swelling or shrinking kinetics of polyelectrolyte gels that undergo volume phase transition as an immobilized enzyme reaction sets in. For this, we studied the coimmobilization of gluconolactonase (GL) with glucose oxidase (GOD). A gel used was in the shape of a small cylinder (several hundred micrometers in diameter) and composed of a lightly cross-linked copolymer of N-isopropylacrylamide and acrylic acid. GL was isolated from Aspergillus niger and purified about 100-fold. It was found that in a substrate solution containing glucose, the gel with the coimmobilized GL and GOD shrinks very rapidly. The shrinking rate was identical to that of the enzyme-free gel that undergoes a shrinking transition in response to a sudden pH change of the outer medium from 7 to 5. This indicates the rate-limiting step in the shrinking process to be diffusion of the networks, but not the enzyme reaction. In the gel with singly immobilized GOD, a very slow shrinking was observed because the process is governed by the enzyme reaction. These results were discussed in full in connection with an enzymatically induced decrease in pH within and in the vicinity of the gel phase. As a result, it has become apparent that the faster shrinking kinetics in the coimmobilized enzyme system is attained by the GL-catalyzed hydrolysis of D-glucono-delta-lactone resulting from the oxidation of glucose with GOD.


Adolescent Blount disease in obese children treated by eight-plate hemiepiphysiodesis.
The aim of this study is to evaluate the outcomes of eight-plate (Orthofix) use during hemiepiphyseodesis operation for growth modulation in obese children with adolescent Blount disease. Six limbs of five consecutive patients who underwent lateral proximal tibial eight-plate (Orthofix) hemiepiphysiodesis were evaluated. The body mass index (BMI) was >30 and the severity of the deformity was in Zone III according to the Mielke and Stevens definition. The mechanical medial proximal tibial angle (MPTA) and the mechanical axis deviation (MAD) were measured preoperatively, postoperatively, and at last follow-up. The outcome of the procedure was established by the degree of tibia vara correction degree at final plate removal or skeletal maturity. Mean age of the patients and mean BMI at the time of surgery was 13 years (range 12 to 14) and 33.5 kg/m2 (range 31 to 36), respectively. Patients were followed for an average of 22 months (range 13 to 31). Preoperative and last follow-up mean values for MPTA were 81 and 80 degrees, respectively. Outcome of the procedure showed two extremities demonstrated progression of the tibia vara (mean of 6.5 degrees), two extremities had no correction of the deformity, and the remaining two extremities showed minimally improvement (mean 3 degrees). The procedure failed to correct the tibia vara in all extremities and all patients were scheduled for an osteotomy to treat the deformity. We do not recommend the use of a tension band plate hemiepiphyseodesis (eight-plate, Orthofix) to treat severe adolescent Blount disease in obese children.


Comparison of Bioelectrical Impedance Analysis with DXA in Adolescents with Cystic Fibrosis before and after a Resistance Training Intervention.
The purpose of this pilot study was to compare body composition metrics obtained by two portable bioelectrical impedance analysis (BIA) devices with dual-energy X-ray absorptiometry (DXA) among adolescents with cystic fibrosis (CF) before and after a resistance exercise training program. Participants with CF were assessed using DXA, single-frequency BIA (SFBIA), and multiple-frequency BIA (MFBIA) to quantify percent body fat (%Fat), fat mass (FM), and fat-free mass (FFM) at baseline and after a home-based resistance training intervention comprised of 36, 1 h sessions completed in 12-14 weeks. Repeated measures analysis of variance, paired samples t-tests, Cohen's d effect sizes, and Pearson's correlations were used to compare differences between and within methods at baseline and post-intervention. Ten participants (15.8 ± 2.2 yr, 60.1 ± 15.1 kg) completed the assessments. At baseline, both SFBIA and MFBIA scales significantly underestimated %Fat and FM and overestimated FFM, with small to moderate effect sizes. Post-intervention, small, non-significant differences were found between DXA and both BIA scales for all body composition metrics. Significant changes in %Fat and FFM were observed with DXA. MFBIA displayed less constant error than SFBIA when compared to DXA for pre- and post-intervention assessments for %Fat (MFBIA: pre and post -2.8 and -0.8 vs. SFBIA: -4.6 and -2.0), FM (-0.4 and -0.4 vs. -3.0 and -1.1), and FFM (+0.8 and +0.6 vs. +3.1 and +1.3). Near-perfect correlations were observed at both time points between DXA and each BIA scale. Conclusions: Portable BIA results should be interpreted with caution, and further validation studies in CF patients are needed prior to clinical use.


[Determination of tyrosine based on the fluorescence quenching by molebrum (VI)].
A new selective and sensitive spectrofluorimetric method for the determination of Tyrosine in beer and grape wine has been developed. This method is based on the quenching of fluorescence of Tyrosine by Molybrum(VI). The exitation and emission wavelengths were found to be 278 and 305 nm, respectively. There was a linear relationship in the range of 0.01-14.4 micrograms.mL-1 for Tyrosine. This method is simple and rapid, and has been applied to the determination of Tyrosine in beer and grape wine with satisfactory results.


[Changes in the adrenal medulla of the rat during immobilization stress].
A combined histofluorescent, light optic and electron microscopic investigation has been performed to study the medulla of the adrenals in intact rats (August strain) and immediately after immobilization for 30 h and 24 h after. In the intact animals heteromorphism of the medulla is demonstrated; this depends on the fact that adrenocytes are at different stages of the secretory cycle. Immobilization for 30 h results in synchronization of secretion; this is determined by adaptation of the adrenal system to immobilization. One day after immobilization restoration of heteromorphism in chromaffinocytes is demonstrated. The changes described are compensatory-adaptive reactions of the adrenal medulla to the stress in the animals survived.


Self-homodyne detection of the light orbital angular momentum.
A simple optical system for the self-homodyne detection of the orbital angular momentum (OAM) carried by optical beams is introduced. We propose two different schemes based on the use of optical hybrids, which could detect the OAM mode number, even when the input beam might be slightly distorted. A balanced receiver is used to perform a self-homodyne measure of the optical signal from two different locations at the beam wavefront.


Computed tomography scanning facilitates the diagnosis of sacroiliitis in patients with suspected spondylarthritis: results of a prospective multicenter French cohort study.
To assess the performance of computed tomography (CT) scanning for ascertaining sacroiliitis in patients with suspected spondylarthritis (SpA). The Echography in Spondylarthritis French cohort consists of 489 patients with suspected SpA. At baseline, all patients underwent clinical examination, HLA-B typing, and pelvic radiography. Pelvic CT scanning was performed if sacroiliitis on radiography was considered uncertain or if patients presented with buttock pain duration of >6 months. A set of 100 paired radiographs and CT scans was read in a blinded manner by 2 radiologists, and the kappa coefficient was used to assess their interreader reliability. One of the radiologists read the 173 available pairs of radiographs and CT scans performed at baseline. After training, interreader reliability was moderate for sacroiliitis grading on radiographs (κ = 0.59), excellent on CT scans (κ = 0.91), and excellent for ascertaining sacroiliitis on both radiographs (κ = 1) and CT scans (κ = 0.96). The first and second readers considered the quality of imaging to be excellent in 66% and 67%, respectively, of the radiographs (κ = 0.88) and in 93% and 92%, respectively, of the CT scans (κ = 0.93). Concordance between radiographs and CT scans was low for sacroiliitis grading (κ = 0.08) or ascertainment (κ = 0.16). Definite sacroiliitis was ascertained on radiographs in 6 patients (3.5%) (confirmed by CT scans in 4 patients) and on CT scans in 32 patients (18.5%). A history of uveitis was associated with definite sacroiliitis on radiographs (P = 0.04) and CT scans (P < 0.0001). Definite sacroiliitis was underestimated by radiography, as compared to CT scanning. CT scanning should facilitate the diagnosis of ankylosing spondylitis in patients with suspected SpA.


Seasonal variations of antimicrobial activity and chemical composition of essential oils extracted from three Citrus limon L. Burm. cultivars.
In order to investigate the seasonal variations of antimicrobial properties and chemical composition of essential oils (EOs), three different cultivars of Citrus limon L. Burm. spp. (Femminello Santa Teresa, Monachello and Femminello Continella) were collected at 6-week intervals, from December 2012 to April 2013, for a total of four harvests. The EOs were extracted from lemon peel by hydro-distillation. The antimicrobial activity, tested by paper disc diffusion method, was evaluated against common food-related pathogenic bacteria (Listeria monocytogenes, Staphylococcus aureus, Salmonella enterica and Enterobacter spp.). EOs were more effective against Gram-positive than Gram-negative bacteria at each collection time, but a strong strain dependence was evidenced. Monachello EOs showed the highest inhibition power. The chemical characterisation of the EOs performed by gas chromatography/mass spectrometry identified from 36 to 42 molecules. The chemical difference registered among samples and seasons may explain the different antimicrobial efficacies recorded.


Wellness within illness: happiness in schizophrenia.
Schizophrenia is typically a chronic disorder and among the most severe forms of serious mental illnesses in terms of adverse impact on quality of life. Yet, there have been suggestions that some people with schizophrenia can experience an overall sense of happiness in their lives. We investigated happiness among 72 outpatients with non-remitted chronic schizophrenia with a mean duration of illness of 24.4 years, and 64 healthy comparison subjects (HCs). Despite continued treatment with antipsychotic medications, the individuals with schizophrenia manifested a mild to moderate level of psychopathology. People with schizophrenia reported lower mean levels of happiness than HCs, but there was substantial heterogeneity within the schizophrenia group. Level of happiness in persons with schizophrenia was significantly correlated with higher mental health-related quality of life, and several positive psychosocial factors (lower perceived stress, and higher levels of resilience, optimism, and personal mastery). However, level of happiness was not related to sociodemographic characteristics, duration of illness, severity of positive or negative symptoms, physical function, medical comorbidity, or cognitive functioning. Except for an absence of an association with resilience, the pattern of correlations of happiness with other variables seen among HCs was similar to that in individuals with schizophrenia. Although happiness may be harder to achieve in the context of a serious mental illness, it nonetheless appears to be a viable treatment goal in schizophrenia. Psychotherapies targeting positive coping factors such as resilience, optimism, and personal mastery warrant further investigation.


Legal status, emotional well-being and subjective health status of Latino immigrants.
Among the many stresses that undocumented Latino immigrants experience, worries about their legal status and preoccupation with disclosure and deportation can heighten the risk for emotional distress and impaired quality of health. To better document these effects, this study examined the relationship between deportation concern and emotional and physical well-being among a group of Latino immigrants in a midwestern city. One-hundred-forty-three persons were recruited through community sources. Fifty-six participants (39%) expressed concern with seeking services for fear of deportation, while 87 did not endorse this concern. Measures of emotional distress, Hispanic immigrant stress and subjective health status were administered. Results indicate that Latino immigrants with concerns about deportation are at heightened risk of experiencing negative emotional and health states (particularly anger), Hispanic immigrant stress associated with extrafamilial factors and substandard health status. Findings inform policymakers of culturally relevant stressors of undocumented Latino immigrants that help to create and perpetuate the health and mental health disparities of this group.


Nicotine effects on general semantic priming in Parkinson's disease.
In young healthy nonsmokers, effects of nicotine on semantic processing have been observed under strategy-based priming procedures but not under more general priming procedures (Holmes, Chenery, & Copland, 2008; Holmes, Chenery, & Copland, 2010). Effects of nicotine under general priming procedures, however, may be mediated by baseline priming levels that are below optimum such as when compromised by disease. Nicotinic mechanisms may be involved in the cognitive sequalae of Parkinson's disease (PD). Evidence suggests that semantic processing may be compromised in PD but the potential benefit of nicotinic stimulation is unknown. This study investigated the effects of nicotine on semantic processing in nonsmokers with PD (n = 12) and nonsmoking matched controls (n = 17) using general priming procedures. Specifically, an automatic priming task (0.15 relatedness proportion, RP, and 200 ms stimulus onset asynchrony, SOA) and a controlled priming task (0.8 RP and 1000 ms SOA) were used. Prime-target category relation (category related, noncategory related) was also manipulated. Transdermal nicotine patches (7 mg/24 h) were administered in a double-blind, placebo-controlled, crossover design. For the automatic task, nicotine did not influence priming effects for PD. Unexpectedly, compromised automatic priming for controls was ameliorated. For the controlled task, nicotine influenced priming effects for PD but not controls. The patterns of priming and nicotine effects across the tasks suggest an age-related slowing of the rate of semantic activation for controls, which may be exacerbated in PD. Overall, the findings indicate that nicotine can improve compromised semantic processing in PD, and also influence semantic processing in healthy older individuals.


[Civil hospital of Zamora de Hidalgo].
The city of Zamora de Hidalgo is home to one of the most important hospitals in the region, built in 1841 and named the Civil Hospital of Zamora. Built following demand for municipal health needs and with the support of the City Council of Zamora and private donations, it functioned as a hostel for pilgrims, the destitute and the sick. It was administered and maintained by residents, subsequently by the mothers of the Sacred Heart of Jesus, and finally by the federal Government. It currently gives the Zamorano community services, and admits sick people from other locations such as Jacona, Jiquilpan, Patamban Ocumicho, Chavinda, Tangancicuaro, Chilchota, and Tangamandapio, among others. It was called the Civil hospital because as the only hospital that operated in Zamora, it ceased to be administered by the Ecclesiastic Chapter, and passed into the hands of the State.


The sociology of popular music, interdisciplinarity and aesthetic autonomy.
This paper considers the impact of interdisciplinarity upon sociological research, focusing on one particular case: the academic study of popular music. 'Popular music studies' is an area of research characterized by interdisciplinarity and, in keeping with broader intellectual trends, this approach is assumed to offer significant advantages. As such, popular music studies is broadly typical of contemporary intellectual and governmental attitudes regarding the best way to research specific topics. Such interdisciplinarity, however, has potential costs and this paper highlights one of the most significant: an over-emphasis upon shared substantive interests and subsequent undervaluation of shared epistemological understandings. The end result is a form of 'ghettoization' within sociology itself, with residents of any particular ghetto displaying little awareness of developments in neighbouring ghettos. Reporting from one such ghetto, this paper considers some of the ways in which the sociology of popular music has been limited by its positioning within an interdisciplinary environment and suggests two strategies for developing a more fully-realized sociology of popular music. First, based on the assumption that a sociological understanding of popular music shares much in common with a sociological understanding of everything else, this paper calls for increased intradisciplinary research between sociologists of varying specialisms. The second strategy, however, involves a reconceptualization of the disciplinary limits of sociology, as it argues that a sociology of popular music needs to accept musical specificity as part of its remit. Such acceptance has thus far been limited not only by an interdisciplinary context but also by the long-standing sociological scepticism toward the analysis of aesthetic objects. As such, this paper offers an intervention into wider debates concerning the remit of sociological enquiry, and whether it is ever appropriate for sociological analyses of culture to consider 'internal' aesthetic structures. In relation to the specific case study, the paper argues that considering musical specificity is a necessary component of a sociology of popular music, and some possibilities for developing a 'materialist sociology of music' are outlined.


A 12-Year Analysis of Nonbattle Injury Among US Service Members Deployed to Iraq and Afghanistan.
Nonbattle injury (NBI) among deployed US service members increases the burden on medical systems and results in high rates of attrition, affecting the available force. The possible causes and trends of NBI in the Iraq and Afghanistan wars have, to date, not been comprehensively described. To describe NBI among service members deployed to Iraq and Afghanistan, quantify absolute numbers of NBIs and proportion of NBIs within the Department of Defense Trauma Registry, and document the characteristics of this injury category. In this retrospective cohort study, data from the Department of Defense Trauma Registry on 29 958 service members injured in Iraq and Afghanistan from January 1, 2003, through December 31, 2014, were obtained. Injury incidence, patterns, and severity were characterized by battle injury and NBI. Trends in NBI were modeled using time series analysis with autoregressive integrated moving average and the weighted moving average method. Statistical analysis was performed from January 1, 2003, to December 31, 2014. Primary outcomes were proportion of NBIs and the changes in NBI over time. Among 29 958 casualties (battle injury and NBI) analyzed, 29 003 were in men and 955 were in women; the median age at injury was 24 years (interquartile range, 21-29 years). Nonbattle injury caused 34.1% of total casualties (n = 10 203) and 11.5% of all deaths (206 of 1788). Rates of NBI were higher among women than among men (63.2% [604 of 955] vs 33.1% [9599 of 29 003]; P < .001) and in Operation New Dawn (71.0% [298 of 420]) and Operation Iraqi Freedom (36.3% [6655 of 18 334]) compared with Operation Enduring Freedom (29.0% [3250 of 11 204]) (P < .001). A higher proportion of NBIs occurred in members of the Air Force (66.3% [539 of 810]) and Navy (48.3% [394 of 815]) than in members of the Army (34.7% [7680 of 22 154]) and Marine Corps (25.7% [1584 of 6169]) (P < .001). Leading mechanisms of NBI included falls (2178 [21.3%]), motor vehicle crashes (1921 [18.8%]), machinery or equipment accidents (1283 [12.6%]), blunt objects (1107 [10.8%]), gunshot wounds (728 [7.1%]), and sports (697 [6.8%]), causing predominantly blunt trauma (7080 [69.4%]). The trend in proportion of NBIs did not decrease over time, remaining at approximately 35% (by weighted moving average) after 2006 and approximately 39% by autoregressive integrated moving average. Assuming stable battlefield conditions, the autoregressive integrated moving average model estimated that the proportion of NBIs from 2015 to 2022 would be approximately 41.0% (95% CI, 37.8%-44.3%). In this study, approximately one-third of injuries during the Iraq and Afghanistan wars resulted from NBI, and the proportion of NBIs was steady for 12 years. Understanding the possible causes of NBI during military operations may be useful to target protective measures and safety interventions, thereby conserving fighting strength on the battlefield.


DEPAS: De-novo Pathology Semantic Masks using a Generative Model.
The integration of artificial intelligence (AI) into digital pathology has the potential to automate and improve various tasks, such as image analysis and diagnostic decision-making. Yet, the inherent variability of tissues, together with the need for image labeling, lead to biased datasets that limit the generalizability of algorithms trained on them. One of the emerging solutions for this challenge is synthetic histological images. Debiasing real datasets require not only generating photorealistic images but also the ability to control the cellular features within them. A common approach is to use generative methods that perform image translation between semantic masks that reflect prior knowledge of the tissue and a histological image. However, unlike other image domains, the complex structure of the tissue prevents a simple creation of histology semantic masks that are required as input to the image translation model, while semantic masks extracted from real images reduce the process's scalability. In this work, we introduce a scalable generative model, coined as DEPAS (De-novo Pathology Semantic Masks), that captures tissue structure and generates high-resolution semantic masks with state-of-the-art quality. We demonstrate the ability of DEPAS to generate realistic semantic maps of tissue for three types of organs: skin, prostate, and lung. Moreover, we show that these masks can be processed using a generative image translation model to produce photorealistic histology images of two types of cancer with two different types of staining techniques. Finally, we harness DEPAS to generate multi-label semantic masks that capture different cell types distributions and use them to produce histological images with on-demand cellular features. Overall, our work provides a state-of-the-art solution for the challenging task of generating synthetic histological images while controlling their semantic information in a scalable way.


Correlative light microscopy and electron tomography to study Von Willebrand factor exocytosis from vascular endothelial cells.
Revealing the ultrastructure and function of fluorescently labeled cellular components by correlative light and electron microscopy (CLEM) facilitates the study of structure-function relationships in complex biological processes. Given the diversity of available fluorescent tags, light microscopy is ideal for monitoring dynamic cellular processes, while electron microscopy reveals the morphological context of structures at high resolution. Endothelial cells lining the blood vessel wall contain storage organelles called Weibel-Palade bodies (WPBs), which contain tubules of densely packed helical spirals of the blood coagulation protein Von Willebrand factor (VWF). Exocytosis of WPBs is triggered upon vascular damage and results in the transformation of stored tubular VWF into secreted extracellular VWF. Upon exocytosis, VWF rearranges into long filamentous strings to recruit platelets from the blood. During this secretion process, large intracellular VWF exocytosis structures are formed called secretory pods. Here, we describe a CLEM method used to study the relationship between the secretory pod and secreted VWF where confocal microscopy on whole cells was combined with serial electron tomography on chemically fixed, plastic-embedded sections. We show that the combination of these two well-established microscopy modalities provides a robust and generic CLEM method suitable for the characterization of VWF secretion sites.


Ang1/Tie2/VE-Cadherin Signaling Regulates DPSCs in Vascular Maturation.
Adding dental pulp stem cells (DPSCs) to vascular endothelial cell-formed vessel-like structures can increase the longevity of these vessel networks. DPSCs display pericyte-like cell functions and closely assemble endothelial cells (ECs). However, the mechanisms of DPSC-derived pericyte-like cells in stabilizing the vessel networks are not fully understood. In this study, we investigated the functions of E-DPSCs, which were DPSCs isolated from the direct coculture of human umbilical vein endothelial cells (HUVECs) and DPSCs, and T-DPSCs, which were DPSCs treated by transforming growth factor beta 1 (TGF-β1), in stabilizing blood vessels in vitro and in vivo. A 3-dimensional coculture spheroid sprouting assay was conducted to compare the functions of E-DPSCs and T-DPSCs in vitro. Dental pulp angiogenesis in the severe combined immunodeficiency (SCID) mouse model was used to explore the roles of E-DPSCs and T-DPSCs in vascularization in vivo. The results demonstrated that both E-DPSCs and T-DPSCs possess smooth muscle cell-like cell properties, exhibiting higher expression of the mural cell-specific markers and the suppression of HUVEC sprouting. E-DPSCs and T-DPSCs inhibited HUVEC sprouting by activating TEK tyrosine kinase (Tie2) signaling, upregulating vascular endothelial (VE)-cadherin, and downregulating vascular endothelial growth factor receptor 2 (VEGFR2). In vivo study revealed more perfused and total blood vessels in the HUVEC + E-DPSC group, HUVEC + T-DPSC group, angiopoietin 1 (Ang1) pretreated group, and vascular endothelial protein tyrosine phosphatase (VE-PTP) inhibitor pretreated group, compared to HUVEC + DPSC group. In conclusion, these data indicated that E-DPSCs and T-DPSCs could stabilize the newly formed blood vessels and accelerate their perfusion. The critical regulating pathways are Ang1/Tie2/VE-cadherin and VEGF/VEGFR2 signaling.


Examining Internalizing Mental Health Correlates of Addiction Severity in Patients Hospitalized With Medical Complications From Substance Use Disorder.
Comorbidities between Substance Use Disorder (SUD) and mental health disorders are highly prevalent, yet there remains a lack of information regarding how mental health conditions may affect addiction severity. Consequently, this study sought to investigate the relationship between internalizing disorders (anxiety and mood disorders) and addiction severity in patients hospitalized for SUD-related medical complications. Individual difference predictors and history of prior treatment for SUD were also examined. Participants (N = 200) were hospitalized patients who consented to receive peer-based recovery support services for their SUD. To be eligible for the study, participants needed to have a SUD diagnosis due to alcohol, opioids, methamphetamine, cocaine, or a combination of these substances (polysubstance use). Participants completed self-report questionnaires regarding demographics, mental health history, prior SUD treatment, and addiction severity (Drug and Alcohol Screening Test; DAST-10) during their hospitalization. Results showed that patients with Generalized Anxiety Disorder (GAD) (M = 6.68, SD = 2.97) had greater addiction severity compared to those without GAD (M = 5.41, SD = 3.34), P = .016. Addiction severity results stratified by SUD type showed that the relationship was significant among patients with Alcohol Use Disorder (P = .014), but not among those with other SUD types (Ps > .27). Major Depressive Disorder (MDD) and Post-Traumatic Stress Disorder (PTSD) were not linked to addiction severity. Among those with GAD, 81.4% had previously been to treatment compared to only 53.1% of those without GAD, P = .010. The only participant characteristic linked with addiction severity was insurance status. GAD may represent a risk factor for advanced alcohol addiction trajectories, including greater addiction severity and severe health complications requiring inpatient hospitalization.


Berezinskii-Kosterlitz-Thouless Paired Phase in Coupled XY Models.
We study the effect of a linear tunneling coupling between two-dimensional systems, each separately exhibiting the topological Berezinskii-Kosterlitz-Thouless (BKT) transition. In the uncoupled limit, there are two phases: one where the one-body correlation functions are algebraically decaying and the other with exponential decay. When the linear coupling is turned on, a third BKT-paired phase emerges, in which one-body correlations are exponentially decaying, while two-body correlation functions exhibit power-law decay. We perform numerical simulations in the paradigmatic case of two coupled XY models at finite temperature, finding evidences that for any finite value of the interlayer coupling, the BKT-paired phase is present. We provide a picture of the phase diagram using a renormalization group approach.


Wdr62 is involved in female meiotic initiation via activating JNK signaling and associated with POI in humans.
Meiosis is a germ cell-specific division that is indispensable for the generation of haploid gametes. However, the regulatory mechanisms of meiotic initiation remain elusive. Here, we report that the Wdr62 (WD40-repeat protein 62) is involved in meiotic initiation as a permissive factor rather than an instructive factor. Knock-out of this gene in a mouse model resulted in female meiotic initiation defects. Further studies demonstrated that Wdr62 is required for RA-induced Stra8 expression via the activation of JNK signaling, and the defects in meiotic initiation from Wdr62-deficient female mice could be partially rescued by JNK1 overexpression in germ cells. More importantly, two novel mutations of the WDR62 gene were detected in patients with premature ovarian insufficiency (POI), and these mutations played dominant-negative roles in regulating Stra8 expression. Hence, this study revealed that Wdr62 is involved in female meiotic initiation via activating JNK signaling, which displays a novel mechanism for regulating meiotic initiation, and mutation of WDR62 is one of the potential etiologies of POI in humans.


The effect of atenolol on the growth hormone response to growth hormone-releasing hormone in obese children.
We have evaluated the effect of acute administration of atenolol, a selective beta-adrenergic antagonist, on the GH response to GHRH in nine obese children and in eight age-matched controls. The GH response to GHRH (1-29, 1 microgram/kg iv), evaluated both as the GH peak and as integrated area under the curve, was significantly lower in the obese children than in the controls. Pretreatment with atenolol (50 or 100 mg orally in subjects with body weight less than or greater than 40 kg, respectively, administered 120 min before the GHRH injection) significantly increased the GH response to GHRH in the obese subjects, such that their mean peak GH levels and mean integrated area under the curve after atenolol plus GHRH were similar to those of the control children after GHRH. Also in control children, atenolol caused a significant augmentation of the GH response to GHRH. Mean peak GH levels and mean integrated area under the curve after atenolol plus GHRH were significantly higher in the controls than in the obese children given the same treatment. These data show that inhibition of central beta-adrenergic receptors counteracts the blunted GH response to GHRH present in the obese children. In view of the alleged mechanism of action of beta-adrenergic blockade (inhibition of endogenous SRIH release), our data suggest that the somatostatinergic system is intact in obesity, and that the suppressed GH secretion is due to other causes.


[Buerger's thromboangiitis obliterans. Pathologico-anatomical analysis of 53 cases].
Fifty-three clinically and morphologically verified cases of thromboangiitis obliterans have been analyzed. The histological characteristics of the disease are described. Male patients predominate in a ratio of 3.4:1. The mean age at the moment of biopsy/amputation was 40.7 years for the male and 44 years for the female patients. The lower extremity was affected in 45 cases (34 male, 11 female) with preference for the lower leg arteries with or without inclusion of the popliteal artery. Only 8 cases (7 male, 1 female) were localized in the upper extremity with preference for the arteries of fingers and hand. The number of female patients with Buerger's disease has gradually increased during recent decades, probably due to increasing nicotine consumption among the female population. Thromboangiitis obliterans is a clinico-pathological entity clearly distinct from juvenile arteriosclerosis.


Estimating the late-life effects of social and emotional skills in childhood using midlife mediators.
Social and emotional skills are known to affect health and non-health outcomes, but there is limited evidence on whether these skills in childhood affect late life outcomes because of a shortage of long-running datasets containing this information. We develop a three-stage procedure and use it to estimate the effect of childhood social and emotional skills on health and labour market outcomes in late-life. This procedure makes use of mediators in midlife which are shown to be predicted by childhood skills in one dataset and to predict late-life outcomes in another dataset. We use this method to combine estimates from the National Child Development Survey and the British Household Panel Survey. We find that childhood skills predict marital status, education, home ownership, income and health at age 46 years and these midlife variables predict levels of quality-adjusted life years and labour income accumulated by age 63 years. The combined estimates suggest a standard deviation increase in average Bristol Social Adjustment Guide total score at ages 7 and 11 is associated with 4.2% (standard error = 0.6%) additional quality-adjusted life years and more than 9.9% (£14,539, standard error = £2072) additional accumulated pre-tax earnings by age 63 years. Therefore, childhood interventions to increase social and emotional skills would be expected to reduce future healthcare costs and increase wealth. Our three-stage methodology can be used to predict the life-course effects of investments in childhood skills by combining results from datasets across population cohorts.


Aha1 competes with Hop, p50 and p23 for binding to the molecular chaperone Hsp90 and contributes to kinase and hormone receptor activation.
The ATP-dependent molecular chaperone Hsp90 (heat-shock protein 90) is essential for the maturation of hormone receptors and protein kinases. During the process of client protein activation, Hsp90 co-operates with cofactors/co-chaperones of unique sequence, e.g. Aha1 (activator of Hsp90 ATPase 1), p23 or p50, and with cofactors containing TPR (tetratricopeptide repeat) domains, e.g. Hop, immunophilins or cyclophilins. Although the binding sites for these different types of cofactors are distributed along the three domains of Hsp90, sterical overlap and competition for binding sites restrict the combinations of cofactors that can bind to Hsp90 at the same time. The recently discovered cofactor Aha1 associates with the middle domain of Hsp90, but its relationship to other cofactors of the molecular chaperone is poorly understood. Therefore we analysed whether complexes of Aha1, p23, p50, Hop and a cyclophilin with Hsp90 are disrupted by the other four cofactors by gel permeation chromatography using purified proteins. It turned out that Aha1 competes with the early cofactors Hop and p50, but can bind to Hsp90 in the presence of cyclophilins, suggesting that Aha1 acts as a late cofactor of Hsp90. In contrast with p50, which can bind to Hop, Aha1 does not interact directly with any of the other four cofactors. In vivo studies in yeast and in mammalian cells revealed that Aha1 is not specific for kinase activation, but also contributes to maturation of hormone receptors, proposing a general role for this cofactor in the activation of Hsp90-dependent client proteins.


Putting it all together: recommendations for improving pain management in plastic surgical procedures: hand surgery.
Approaches to upper extremity anesthesia in hand surgery include regional blocks, wide-awake hand surgery with local anesthesia, and stellate ganglion blocks. Retrospective review of the literature from 2000 to 2014 published on the delivery of local and regional anesthesia during hand surgery. Included studies describe techniques of administration and treatment outcomes to identify common practices of pain management in hand surgery. Regional blocks provide sufficient anesthesia for hand surgery and have been found to improve postoperative pain and measured outcome scores. Wide-awake surgery offers many advantages including minimizing anesthetic risk and expense, permitting patient participation in operative evaluation, decreasing hospital time, and improving functional outcomes scores. Pain management in hand surgery can be achieved through regional blocks and wide-awake techniques that do not necessitate general anesthesia in an effort to improve safety, convenience, cost savings, and efficiency.


The Pattern of Underlying Cause of Death in Patients with Inflammatory Bowel Disease in England: A Record Linkage Study.
Numerous studies have established that mortality risk in inflammatory bowel disease [IBD] patients is higher than in the general population, but the causes of death have seldom been examined. We aimed to describe causes of death in IBD. A matched cohort study using UK general practice data from Clinical Practice Research Datalink linked to death registration records. We described the distribution of causes of death among IBD patients by age at death and time since IBD diagnosis. We estimated age-specific mortality rates and hazard ratios of death in multivariable Cox proportional hazards models. 20293 IBD patients were matched to 83261 non IBD patients. The mortality rate was 40% higher in IBD patients [2005 deaths] than in non IBD patients [6024 deaths] (adjusted overall hazard ratio: = 1.4, 95% confidence interval [CI]: = 1.4-1.5], with greater risk of death in Crohn's disease [hazard ratio: = 1.6, 1.5-1.7] than in ulcerative colitis [1.3, 1.3-1.4]. Causes attributable to IBD constituted 3.7% of all deaths in ulcerative colitis and 8.3% in Crohn's disease. Among IBD patients, death was less likely to be due to circulatory, respiratory or neoplastic diseases than among non IBD patients. In both IBD and non IBD patients all these causes became more clinically important with advancing age, with the commonest neoplastic cause of death being lung cancer rather than gastrointestinal cancers. IBD patients have an additional risk of death. Most IBD patients die of circulatory or respiratory causes, and the contribution to mortality from long-term complications of IBD is clinically less important.


A qualitative analysis of critical incident reporting in a paediatric hospital: benefits and weaknesses.
The value of critical incident reporting systems (CIRSs) has been shown before but data for paediatric facilities are scarce. We aimed to evaluate a CIRS in a paediatric hospital to analyse its benefits, weaknesses and opportunities. In a qualitative analysis, all incidents reported in 2018 with the anonymous reporting tool (CIRS) of the Children's Hospital Lucerne were evaluated. In an iterative process, categories to group the incidents were created and the data analysed accordingly. The focus was on the problem created through the incident, the type of error and possible avoidance. 496 incidents were reported in 2018: 307 incidents led to medical errors directly effecting patients, 82 incidents led to organisational problems increasing expenditure and 107 incidents were found to not result in any problem. In the majority of cases (398/496) there was no evidence that the caregiver responsible was informed. Personal feedback was documented in 46 cases. Fifty-two incidents were self-reported. A number of reported incidents helped to identify system-based errors and for these the reporting system proved indispensable. Many of the reported errors were found to have an individual component, or only organisational or no consequences. Our data give evidence that instead of giving direct personal feedback, the anonymous reporting system was utilised. The CIRS is essential to identify system-based errors, but personal feedback needs to become obligatory so caregivers can learn from their error: an additional tool to ensure individual feedback and overcome communication difficulties needs to be created.


Effects of different embedding gels on periostealchondrogenesis in vitro.
To develop a more useful organ culture model for periosteal chondrogenesis in vitro, we compared the effects of the embedding of explants in agarose versus collagen gels. Chondrogenic differentiation was examined by means of histological observation and in terms of the expression of mRNA encoding two cartilage markers, Type II collagen and Aggrecan. Periosteal explants were derived from the tibiae of rabbits. These explants were embedded in either agarose gel or collagen gel and cultured for 6 weeks. Histological examinations revealed that in the agarose gel, cells were neither present in the explants nor in the gel. In the collagen gel, cells migrated from the explanted tissues into the gel, and some cells were round. However, no explants showed safranin-O staining. Only 10% of 10 surviving explants in the agarose gel expressed the Type II collagen gene and the Aggrecan gene. On the other hand, of 25 surviving explants in the collagen gel, the expression of the Type II collagen gene was detected in 18 explants (72%) and that of the Aggrecan gene was detected in 21 explants (84%). In conclusion, we demonstrated that the periosteum exerts chondrogenesis in certain circumstances and its chondrogenesis is closely related to the culture material.


Optimized orthodontic palatal miniscrew implant insertion angulation: a finite element analysis.
There is a controversial body of evidence regarding optimal insertion angulation of an orthodontic miniscrew as a mean of skeletal anchorage. A bracket head-type 8-mm-long miniscrew (60-degree symmetrical trapezoid thread, 0.1-mm thread fillet, 0.2-mm thread height, with 0.5-mm thread pitch) was designed and monocortically inserted at 30, 45, 55, 70, 90, 110, 125, 135, and 150 degrees of inclination to the surface of bone. A bilayer cortical (1.6 mm) and cancellous (8.5 mm) bone model was constructed, adopted from a 22-year-old male patient's cone beam computed tomography (CBCT) image of his anterior hard palate area. A horizontal force of 2 N was applied parallel to the bone surface. Bone material was simulated as normal and osteoporotic bone. The maximum equivalent von Mises stress and microstrain values were separately calculated for the miniscrew, cortical bone, and cancellous bone. Deflections of the whole bone and miniscrew were also reported. A significant lower stress was found in the cancellous bone compared to the cortical bone. Osteoporotic bone displayed higher strain values. Overall, 30-degree models exhibited the lowest von Mises stress and strain values for the cortical layer and miniscrew in both normal and osteoporotic models. Meanwhile, 90-degree models displayed the lowest strain values in the osteoporotic and normal cancellous bones. Minimum bone and miniscrew deflection values were related to the model of 30-degree insertion angulation. These results showed that, within the limitations of the study, the 30-degree angulation of miniscrew insertion toward the direction of applied force could lower the cortical bone stress and strain.


Ocular presentations of breast cancer.
Breast cancer is the most common malignancy in women, with increasing incidence in Europe and North America. The frequency of involvement of the eye and visual pathways is reported to be as high as 30% in patients with known metastatic disease. In some cases, ophthalmic involvement can be the first sign of metastatic spread. Metastasis occurs via the haematogenous route and predominantly involves the choroid. Metastases to other ocular structures, the orbit and the visual pathways have also been described. Paraneoplastic effects are rare but significant. Different modalities are employed in the treatment of breast cancer and its metastases. These include chemotherapy and radiotherapy. The ocular adverse effects of these have been well described, but recently developed new treatment modalities, such as monoclonal antibodies, may have different side-effects. With the increasing incidence of breast cancer and the advent of new treatment strategies, the complications of the disease and the sequelae of therapy are highly relevant to both oncologists and ophthalmologists.


Treatment patterns and health care resource use in patients receiving multiple lines of therapy for metastatic squamous cell carcinoma of the head and neck in the United Kingdom.
This study evaluated the patterns of care and health care resource use (HCRU) in patients with metastatic squamous cell carcinoma of the head and neck (SCCHN) who received ≥3 lines of systemic therapy in the United Kingdom (UK). Oncologists (n = 40) abstracted medical records for patients with metastatic SCCHN who initiated third-line systemic therapy during 1 January 2011-30 August 2014 (n = 220). Patient characteristics, treatment patterns and SCCHN-related HCRU were summarised descriptively for the metastatic period; exploratory multivariable regression analyses were conducted on select HCRU outcomes. At metastatic diagnosis, most patients had an Eastern Cooperative Oncology Group performance status (PS) of 0/1 (95%). For patients with PS 0/1, the most common first-line treatment was cisplatin+5-fluorouracil (5-FU); docetaxel was the most common second- and third-line treatment. For patients with PS ≥ 2, the most common first-, second-, and third-line treatments were carboplatin+5-FU, cetuximab, and methotrexate, respectively. Most patients received supportive care during (85%) and after (89%) therapy. This study provides useful information, prior to the availability of immunotherapy, on patient characteristics, treatment patterns, HCRU, and survival in a real-world UK population with metastatic SCCHN receiving ≥3 lines of systemic therapy. Patterns of care and HCRU varied among patients with metastatic SCCHN; specific systemic therapies varied by patient PS.