The role of CT analyses of the sternal end of the clavicle and the first costal cartilage in age estimation.
The ossification patterns of medial clavicle and the first costal cartilage represent interesting features of the same anatomical region which are accessible for conventional radiographic and computed tomography (CT) examinations in the same field of view. This study encompassed Serbian population and was carried out to examine whether CT analyses of medial clavicle and the first costal cartilage could be successfully applied, either individually or conjointly, in the age assessment. The study was based on CT examinations of thoracic region of 154 patients, aged between 15 and 35 years. Besides radiodensity and stages of epiphyseal cartilage ossification of medial clavicle, the study detected other features that expressed significant correlation with age, such as calculated anterior to posterior cortical thickness ratio, medullar canal diameter, and clavicular shaft diameter. However, although calculated ossified and calcified linear projections' (OCP) stages correlated to age, the distinction between stages was not satisfying. The interaction between the ossification status of medial clavicle and OCP was not significantly influenced by age. The results of our study outlined interesting new age predictors with mutual relationship: acquired radio density of the sternal epiphyseal-metaphyseal region and radio density of the first costal cartilage. Intersex variability was observed in several age-related features: calculated anterior to posterior cortical thickness ratio, diameter of medullar canal, and diameter of the clavicular shaft. Altogether, our study identified several radiological features of the first costal cartilage and medial clavicle that correlated with age and which could be applied as additional guidance for age estimation in each specific case.


Seeking and engaging in internet sex: a survey of patients attending genitourinary medicine clinics in Plymouth and in London.
We conducted a survey of patients attending two GUM clinics to evaluate the use of the internet for seeking sexual partners and for seeking on-line sexual health information. Prevalence of internet sex-seeking (ISS) was 11% (57/500) in Plymouth and 21% (50/237) in London. ISS was more common among men who have sex with men (MSM) (43/92 = 47%) than men who have sex with women (MSW) (38/280 = 14%, P < 0.0001) and more common amongst MSW than women who have sex with men (WSM) (25/350 = 7%, P = 0.007). In both samples, accessing sexual health information online was associated with ISS (Plymouth, P = 0.05 and London, P = 0.001), as was reporting more than 10 sexual partners per year (Plymouth and London, P < 0.001). It remains to be seen whether the potential sexual health promotion benefits of the internet could balance potential risks of STI acquisition.


Effect of prematurity on protein glycosylation in the newborn.
Glycohemoglobins (GHb) are the products of irreversible non-enzymatic reactions between glucose and the hemoglobin molecule. Glycosylation of proteins in general can modify protein structure and alter catalytic properties, thereby causing cellular dysfunction. The aim of the present study was to test the hypothesis that protein glycosylation levels in premature infants are elevated compared with full-term infants (neonates). Blood GHb levels in pre-term and full-term infants were studied, and the in vitro glycosylation of erythrocytes obtained from both pre-term and full-term infants was assessed. Cord-blood from 31 pre-term and 11 full-term infants was collected and GHb levels were determined using affinity columns. Erythrocytes from the cord blood of 17 additional infants (eight pre-term, ≤ 36 weeks gestation, and nine full-term, ≥ 37 weeks gestation) were obtained and incubated for 24 h in a high-glucose medium. Baseline and post-incubation GHb levels were calculated to determine the in vitro susceptibility of pre-term versus full-term infants to glycosylation. Blood GHb levels were significantly higher (P < 0.01) in full-term compared with pre-term infants. The percent increase in GHb formation in vitro was similar between the erythrocytes of full-term and those of pre-term infants. Contrary to the original hypothesis, the erythrocytes of pre-term infants do not show increased glycosylation of proteins when compared with those of full-term infants.


Complications following total hip arthroplasty and hemiarthroplasty for femoral neck fractures in patients with a history of lumbar spinal fusion.
The purpose of this study was to examine whether previous lumbar spinal fusion (LSF) was an independent risk factor for complications in patients undergoing total hip arthroplasty (THA) or hemiarthroplasty for displaced femoral neck fractures. An administrative database was queried from 2010 to Q2 of 2019 to analyze and compare complications in patients undergoing either THA or hemiarthroplasty for femoral neck fracture with a history of LSF versus no history of LSF. Joint complications including periprosthetic fracture, prosthetic joint infection (PJI), prosthetic joint dislocation (PJD), aseptic loosening, and prosthetic revision were examined at 90 days and 1 year post-operatively. In the THA cohort, patients with prior LSF had significantly higher likelihood of aseptic loosening at 90 days and 1 year post-operatively in comparison to those without prior LSF (90-day: OR 2.22; 1-year: OR 1.95). Patients in the hemiarthroplasty cohort with prior LSF had significantly higher likelihood of PJI (90-day: OR 2.18; 1-year: OR 2.37), aseptic loosening (90-day: OR 3.42; 1-year: OR 4.68), and prosthetic revision (90-day: OR 2.27; 1-year: OR 2.25) in both the 90-day and 1-year postoperative period in comparison to those without prior LSF. Additionally, for the same cohort, periprosthetic fracture (1-year: OR 2.32) and PJD (1-year: OR 2.31) were significantly higher at 1-year postoperative. Presence of LSF was found to be an independent risk factor for increased joint complications in patients undergoing either a THA or hemiarthroplasty for displaced femoral neck fractures.


[Disease management guidelines in dermatology: implementation, potentials and limitations exemplified by the guidelines for the management of hand eczema].
In Germany, the "Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften" (AWMF; consortium of scientific medical societies) constitutes the umbrella organisation to conceive, evaluate, and release guidelines. There are 3 stages of development (S1-S3) according to the evidence level and the process of consensus finding. Currently, 59 dermatologic guidelines have been published under the auspices of the Deutsche Dermatologische Gesellschaft (German Dermatological Society). The guideline for the management of hand dermatitis (AWMF-Register-No: 013/053) is an instructive recent example. This guideline clearly demonstrates the benefits of guidelines, i.e. standardized definition of heterogeneous diseases and disease severity as well as standardized therapy algorithms. This is especially important in diseases difficult-to-treat like chronic hand dermatitis. The effective implementation of guidelines with early incorporation of new therapies, for example alitretinoin in the therapy of hand dermatitis, can considerably improve the quality of life of patients.


Visible-light hydrogen generation using as photocatalysts layered titanates incorporating in the intergallery space ruthenium tris(bipyridyl) and methyl viologen.
A series of layered titanates containing in the interlayer space tris(2,2'-bipyridyl)ruthenium(II) [Ru(bpy)(3)(2+)] or methyl viologen (MV(2+)) or both has been prepared and characterized by elemental analyses, XRD, and optical and vibrational spectroscopy. Incorporation of Ru(bpy)(3)(2+) and MV(2+) is confirmed by the increase of the distance between the titanate layers. The presence of Ru(bpy)(3)(2+) in the material is also revealed in optical spectroscopy where the ligand to metal charge transfer band appearing at λ(max) 460 nm is observed. Also incorporation of MV(2+) leads to the observation of the charge transfer complex band with the titanate host from 350 to 650 nm. These solids are active for the photocatalytic hydrogen generation from water when colloidal platinum as catalyst and EDTA as sacrificial electron donor are present in the solution. The maximum efficiency was obtained for a solid consisting of layered titanate containing a 10.2 wt.% loading of Ru(bpy)(3)(2+) incorporated in the titanate layers and MV(2+) and Pt nanoparticles in the aqueous solution. This heterogeneous system produced about one-half the hydrogen generated for the conventional homogeneous system where all the components [Ru(bpy)(3)(2+), MV(2+), Pt, and EDTA] are in solution, with the advantage that it can be used as film or recovered by filtration from the aqueous medium.


Cloxacillin nanostructured formulation for the treatment of bovine keratoconjunctivitis.
Infectious bovine keratoconjunctivitis (IBK) is a widespread, contagious ocular disease that affects cattle, especially dairy breeds. The disease is caused by Gram-negative bacteria mainly Moraxella bovis, and its treatment consists of parenteral or topic antibiotic therapy. The topic treatment approach is used more commonly in lactating cows, to avoid milk disposal. However, treatment failures are common, because the antibiotic is removed during lacrimation. This study aimed to evaluate the susceptibility of commercial cloxacillin and evaluate the efficacy of nanostructured cloxacillin in clinical cases of IBK by Moraxella. The minimum inhibitory concentration (MIC) of nanoparticle cloxacillin nanocoated, the nanoparticle without the antibiotic and the commercial cloxacillin were determined in vitro with field samples of Moraxella ovis (5) and Moraxella bovis (5). The efficiency of nanoparticles was tested in three cows naturally infected that were treated with 1.0 mL (with 0.32 mg of nanostructured cloxacillin) for the ocular route. Moraxella bovis was isolated and identified by biochemical and molecular methods before the treatment. The animals were treated every 12 h for six days. The cure was considered by the absence of clinical symptoms and bacteria after treatment. The mucoadhesive nanoparticle-based formulation promoted clinical cure with a low number of doses of antibiotics, probably due to the maintenance of the MIC in the ocular mucosa for longer due to the mucoadhesive characteristics of the nanoparticle. The results indicate that the use of nanocoated cloxacillin is possible to control infectious bovine keratoconjunctivitis.


Evaluating the Impact of the Pandemic Crisis on the Aviation Industry.
This paper investigates the intellectual structure of the literature addressing "epidemic/pandemic" and "aviation industry" through a bibliometric approach to the literature from 1991 to 2021. The final count of 856 publications was collected from Web of Science and analyzed by CiteSpace (version 5.8.R1) and VOS Viewer. Visualization tools are used to perform the co-citation, co-occurrence, and thematic-based cluster analysis. The results highlight the most prominent nodes (articles, authors, journals, countries, and institutions) within the literature on "epidemic/pandemic" and "aviation industry." Furthermore, this study conceptualizes and compares the growth of literature before theCOVID-19 pandemic and during the COVID-19 ("hotspot") era. The conclusion is that the aviation industry is an engine for global economics on the road to recovery from COVID-19, in which soft (human) resources can play an integral part.


Complex loading affects intervertebral disc mechanics and biology.
Complex loading develops in multiple spinal motions and in the case of hyperflexion is known to cause intervertebral disc (IVD) injury. Few studies have examined the interacting biologic and structural alterations associated with potentially injurious complex loading, which may be an important contributor to chronic progressive degeneration. This study tested the hypothesis that low magnitudes of axial compression loading applied asymmetrically can induce IVD injury affecting cellular and structural responses in a large animal IVD ex-vivo model. Bovine caudal IVDs were assigned to either a control or wedge group (15°) and placed in organ culture for 7 days under static 0.2MPa load. IVD tissue and cellular responses were assessed through confined compression, qRT-PCR, histology and structural and compositional measurements, including Western blot for aggrecan degradation products. Complex loading via asymmetric compression induced cell death, an increase in caspase-3 staining (apoptosis), a loss of aggrecan and an increase in aggregate modulus in the concave annulus fibrosis. While an up-regulation of MMP-1, ADAMTS4, IL-1β, and IL-6 mRNA, and a reduced aggregate modulus were induced in the convex annulus. Asymmetric compression had direct deleterious effects on both tissue and cells, suggesting an injurious loading regime that could lead to a degenerative cascade, including cell death, the production of inflammatory mediators, and a shift towards catabolism. This explant model is useful to assess how injurious mechanical loading affects the cellular response which may contribute to the progression of degenerative changes in large animal IVDs, and results suggest that interventions should address inflammation, apoptosis, and lamellar integrity.


Olfactory and taste dysfunction among mild-to-moderate symptomatic COVID-19 positive health care workers: An international survey.
To determine the prevalence of olfactory and taste dysfunction (OD; TD) among COVID-19 positive health care workers (HCWs), their associated risk factors and prognosis. Between May and June 2020, a longitudinal multicenter study was conducted on symptomatic COVID-19 PCR confirmed HCWs (COVID-19 positive) in London and Padua. Hundred and fourteen COVID-19 positive HCWs were surveyed with a response rate of 70.6% over a median follow-up period of 52 days. UK prevalence of OD and TD was 73.1% and 69.2%, respectively. There was a male to female ratio of 1:3 with 81.6% being white, 43.7% being nurses/health care assistants (HCAs), and 39.3% being doctors. In addition, 53.2% of them worked on COVID-19 wards. Complete recovery was reported in 31.8% for OD and 47.1% for TD with a 52 days follow-up. The job role of doctors and nurses negatively influenced smell (P = .04 and P = .02) and taste recovery (P = .02 and P = .01). Ethnicity (being white) showed to positively influence only taste recovery (P = .04). Sex (being female) negatively influenced OD and TD recovery only in Paduan HCWs (P = .02 and P = .011, respectively). Working on a COVID-19 ward did not influence prognosis. The prevalence of OD and TD was considerably higher in HCWs. The prognosis for OD and TD recovery was worse for nurses/HCAs and doctors but working on a COVID-19 ward did not influence prognosis. Sixty-eight percent of surveyed HCWs at 52 days continued to experience OD or TD requiring additional future medical management capacity. 4.


Safety of Non-steroidal Anti-inflammatory Drugs as Part of Enhanced Recovery After Laparoscopic Sleeve Gastrectomy-A Systematic Review and Meta-Analysis.
Laparoscopic sleeve gastrectomy (LSG) is an effective bariatric surgery option for managing extreme obesity in most patients. While non-steroidal anti-inflammatory drugs (NSAIDs) promise postoperative pain management after bariatric surgeries, their safety in LSG remains unexplored. In this systematic review, we studied the safety of NSAIDs following LSG reported by six studies involving 588 patients. Our study demonstrated that NSAIDs effectively alleviated the postoperative pain after LSG without major safety concerns. Most reported (>20% incidence) adverse events included postoperative nausea and vomiting (PONV, 21%). For patients undergoing LSG, NSAIDs offer a valuable option for pain management and improved care, potentially reducing opioid consumption. However, additional research is required to optimize NSAID usage and ensure safety, especially concerning renal and gastrointestinal issues.


Medical error prevention in ED triage for ACS: use of cardiac care decision support and quality improvement feedback.
Medical errors in the care of patients who present with acute coronary syndrome (ACS)include errors in emergency department (ED) triage, such as the decision to send home a patient who presents with ACS or to hospitalize a patient who does not have ACS to the cardiac care unit (CCU), and errors in treatment, such as the failure to promptly use reperfusion therapy for patients who present with ST-elevation acute myocardial infarction(AMI). ECG-based acute cardiac ischemia time-insensitive predictive instrument(ACI-TIPI) and thrombolytic predictive instruments (TPIs), with a linked TIPI information system (TIPI-IS), provide real-time, concurrent, and retrospective decision support tools and feedback for the prevention of medical errors in the care of patients who present with ACS. In real-time, ACI-TIPI probabilities printed on the ECG header for the ED physician, provide an additional piece of information for triage decision making, and the ACI-TIPI Risk Management form reduces liability risk by prompting consideration and documentation of key clinical factors in the diagnosis of ACI. Also in real-time, the TPI increases overall coronary reperfusion therapy use. Concurrent flagging by TIPI-IS uses electronically acquired ECG and hospital data to provide concurrent alerts about potential misdiagnosis or mis-triage of patients with ACS. Retrospectively TIPI-IS-based feedback reports allow performance improvement. These examples of information technology tools integrated into ECG equipment already used in hospitals to deliver patient care demonstrate the potential to adapt other existing equipment or other patient care activities to enhance patient safety and error reduction.


Hepatocytes mediate coenzyme A transfer to specific carbohydrate-derivatized surfaces.
Freshly isolated chicken and rat hepatocytes adhere with carbohydrate specificity to surfaces derivatized with N-acetylglucosamine and galactose respectively. Previously (Brandley, B.K. and Schnaar, R.L. (1985) J. Biol. Chem. 260, 12474-12483) we reported that metabolically radiolabeled chicken hepatocytes covalently transferred phosphate radiolabel specifically to N-acetylglucosamine-derivatized surfaces. We now report that rat hepatocytes transfer phosphate radiolabel specifically to galactose-derivatized surfaces. Transferred radiolabel from both species to their appropriate carbohydrate-derivatized surface was identified as CoASH. After specific adhesion via the appropriate carbohydrate, CoASH is apparently released from cells and undergoes disulfide exchange with the cleavable immobilization linker we used to tether the sugars to the artificial surfaces. Although CoASH from lysed cells can undergo similar disulfide exchange, the data suggest that other, perhaps physiological mechanisms may be responsible for the carbohydrate-specific radiolabel transfer.


Mixed Dimensional Nanostructure (UiO-66-Decorated MWCNT) as a Nanofiller in Mixed-Matrix Membranes for Enhanced CO2 /CH4 Separation.
Mixed-matrix membranes (MMMs) with combination of two distinct dimensional nanofillers (such as 1D-3D, 2D-3D, or 3D-3D, etc.) have drawn special attention for gas separation applications due to their concerted effects on gas permeation and mechanical properties. An amine-functionalized 1D multiwalled carbon nanotube (NH2 -MWCNT) with exceptional mechanical strength and rapid gas transport was crosslinked with an amine-functionalized 3D metal-organic framework (UiO-66-NH2 ) with high CO2 affinity in a Schiff base reaction. The resultant crosslinked mixed-dimensional nanostructure was used as a nanofiller in a polysulfone (PSf) polymer matrix to explore the underlying synergy between 1D and 3D nanostructures on the gas separation performance of MMMs. Cross-sectional scanning electron microscopy and mapping revealed the homogenous dispersion of UiO-66@MWCNT in the polymer matrix. The MMM containing 5.0 wt. % UiO-66@MWCNT demonstrated a superior permeability 8.3 Barrer as compared to the 4.2 Barrer of pure PSf membrane for CO2 . Moreover, the selectivity (CO2 /CH4 ) of this MMM was enhanced to 39.5 from the 28.0 observed for pure PSf under similar conditions of pressure and temperature.


Absence of short period interspersion of repetitive and non-repetitive sequences in the DNA of Drosophila melanogaster.
A sensitive search has been made in Drosophila melanogaster DNA for short repetitive sequences interspersed with single copy sequences. Five kinds of measurements all yield the conclusion that there are few short repetitive sequences in this genome: () Comparison of the kinetics of reassociation of short (360 nucleotide) and long (1,830 nucleotide) fragments of DNA; 2) reassociation kinetics of long fragments (2,200 nucleotide) with an excess of short (390 short nucleotide) fragments; 3) measurement of the size of S1 nuclease resistant reassociated repeated sequences; 4) measurement of the hyperchromicity of reassociated repetive fragments as a function of length; 5) direct assay by kinetics of reassociation of the amount of single copy sequence present on 1,200 nucletodie long fragments which also contain repetitive sequences.


Expression of B-cell surface antigens in subpopulations of exosomes released from B-cell lymphoma cells.
Exosomes are small (30- to 100-nm) vesicles secreted by all cell types in culture and found in most body fluids. A mean of 1 mL of blood serum, derived from healthy donors, contains approximately 10(12) exosomes. Depending on the disease, the number of exosomes can fluctuate. Concentration of exosomes in the bloodstream and all other body fluids is extremely high. Several B-cell surface antigens (CD19, CD20, CD22, CD23, CD24, CD37, CD40, and HLA-DR) and the common leukocyte antigen CD45 are interesting in terms of immunotherapy of hematologic malignant neoplasms. The established standard for exosome isolation is ultracentrifugation. However, this method cannot discriminate between exosome subpopulations and other nanovesicles. The main purpose of this study was to characterize CD81(+) and CD63(+) subpopulations of exosomes in terms of these surface markers after release from various types of B-cell lymphoma cell lines using an easy and reliable method of immunomagnetic separation. Western blotting, flow cytometry, and electron microscopy were used to compare the total preenriched extracellular vesicle (EV) pool to each fraction of vesicles after specific isolation, using magnetic beads conjugated with antibodies raised against the exosome markers CD63 and CD81. Magnetic bead-based isolation is a convenient method to study and compare subpopulations of exosomes released from B-cell lymphoma cells. The data indicated that the specifically isolated vesicles differed from the total preenriched EV pool. CD19, CD20, CD24, CD37, and HLA-DR, but not CD22, CD23, CD40, and CD45, are expressed on exosomes from B-cell lymphoma cell lines with large heterogeneity among the different B-cell lymphoma cell lines. Interestingly, these B-cell lymphoma-derived EVs are able to rescue lymphoma cells from rituximab-induced complement-dependent cytotoxicity. Distribution of exosomes that contain CD19, CD20, CD24, CD37, and HLA-DR may intercept immunotherapy directed against these antigens, which is important to be aware of for optimal treatment. The use of an immunomagnetic separation platform enables easy isolation and characterization of exosome subpopulations for further studies of the exosome biology to understand the potential for therapeutic and diagnostic use.


Polyphosphate metabolism by purple non-sulfur bacteria and its possible application on photo-microbial fuel cell.
A purple non-sulfur bacterium, Rhodopseudomonas palustris G11, was isolated from an activated sludge plant that treats domestic wastewater. This isolation resulted in the effective accumulation of polyphosphate in cells upon reaching the stationary growth phase. However, when the carbon and/or energy source were/was removed, this bacterium released intracellular polyphosphate or poly-β-hydroxybutyrate to obtain energy to grow or maintain its growth. Furthermore, a novel photo-microbial fuel cell (PMFC) design was proposed. The unique capability of purple non-sulfur bacteria to capture light energy for polyphosphate accumulation was maximized. After R. palustris G11 accumulated considerable polyphosphate and was transferred to a fresh medium, the PMFC system exhibited a maximum voltage of approximately 0.03 V undt illumination. The chemical oxygen demand removal efficiency, Coulomb efficiency, and power density were 95.8%, 0.62%, and 0.15 mW/m2, respectively. The test microorganisms converted most of the light energy in growth and caused the low power production. The microorganisms grew slowly and produced less power under dark conditions than under light illumination. However, these microorganisms used the previously stored polyphosphate or poly-β-hydroxybutyrate for electricity production when they were incubated in a growth-insufficient condition. This novel concept can be improved and optimized in the future for new PMFC applications, such as rechargeable cells, to treat wastewater and restore energy simultaneously.


Characterizing the air pollution of the cities in the closure of corona virus disease 2019 in China.
With the rapid development of industrialization and urbanization in China, energy and vehicle consumption have continued to increase in recent years and air pollution has become serious. In early 2020, Corona Virus Disease 2019 broke out in Wuhan, China. From January 29, 2020, several sources of the air pollution almost all stopped working, including gasoline burning vehicles, dust producing building sites, coal-fired factories, etc. Five indicators of the atmospheric environmental quality were observed from December 19, 2019 to April 30, 2020 in nine cities and 1-h average concentrations, 24-h average concentrations and Air Quality Index were assessed. The 1-h average concentrations of the nitrogen dioxide, the ozone and the sulfur dioxide showed obvious difference though the closure did not change the sequence of the five pollutants' concentrations in the air at diverse sampling moments. The changing of the 24-h average concentrations of the five pollutants indicated the amount of pollutants in the air were greatly affected by human activities. The nitrogen dioxide, the sulfur dioxide and the particulate matters decreased obviously in the closure. The air in the metropolis and the south-east cities were relatively clean and the pollutants' concentrations decreased slightly during the closure period. The northern and the heavy industrial cities showed significant drop on air pollution indicators and the air quality of the two city groups could be greatly improved if some effective measures could be taken of environmental management and regional development.


DLL1 orchestrates CD8+ T cells to induce long-term vascular normalization and tumor regression.
The immunosuppressive and hypoxic tumor microenvironment (TME) remains a major obstacle to impede cancer immunotherapy. Here, we showed that elevated levels of Delta-like 1 (DLL1) in the breast and lung TME induced long-term tumor vascular normalization to alleviate tumor hypoxia and promoted the accumulation of interferon γ (IFN-γ)-expressing CD8+ T cells and the polarization of M1-like macrophages. Moreover, increased DLL1 levels in the TME sensitized anti-cytotoxic T lymphocyte-associated protein 4 (anti-CTLA4) treatment in its resistant tumors, resulting in tumor regression and prolonged survival. Mechanically, in vivo depletion of CD8+ T cells or host IFN-γ deficiency reversed tumor growth inhibition and abrogated DLL1-induced tumor vascular normalization without affecting DLL1-mediated macrophage polarization. Together, these results demonstrate that elevated DLL1 levels in the TME promote durable tumor vascular normalization in a CD8+ T cell- and IFN-γ-dependent manner and potentiate anti-CTLA4 therapy. Our findings unveil DLL1 as a potential target to persistently normalize the TME to facilitate cancer immunotherapy.


The important balance between cytokines derived from type 1 and type 2 helper T cells in the control of graft-versus-host disease.
We have investigated cytokine mRNA expression in the peripheral blood mononuclear cells of 20 patients who received allogeneic hematopoietic stem cell transplants to assess the cytokine network after transplantation. IL-4 mRNA expression decreased in five of five (100%) patients with > or = grade III (severe) acute GVHD and increased in 10 of 22 (45%) patients without severe GVHD. In contrast, IL-12 mRNA expression increased in two of two (100%) patients with severe GVHD, but increased in only six of 18 (33%) patients without severe GVHD. Furthermore, IL-10 and/or IL-13 mRNA expression increased in 19 of 22 (86%) patients without severe GVHD, but increased in only one of three (33%) patients with severe GVHD. In patients with allogeneic PBSCT who had severe acute GVHD, the cytokine mRNA expression in patients with allogeneic PBSCT, who had no severe GVHD, showed a similar pattern to that in patients with allogeneic BMT. IL-4 mRNA expression increased in three of five (60%) patients and IL-10 and/or IL-13 mRNA expression increased in five of five (100%) patients. In contrast, IL-12 mRNA expression increased in only one of three (33%) patients. Serum IL-4 concentration in allogeneic PBSCT patients in the early engraftment phase was relatively high, while serum IL-12 concentration was low. These findings suggest that severe GVHD may be related to the cytokine imbalance between type 1 helper T (Th1) cells and type 2 helper T (Th2) cells.


A developmental study of retinal afferents and visual responses in the cat pretectum.
Neuronal responses in the pretectum (PT) were analyzed in 4-16 week old kittens after visual and electrical stimulation and compared with adult responses from a previous study. All three retinal fiber types projecting to the adult PT could be electrically activated in kittens from 4 weeks on. There was a dramatic reduction of response latencies to electric shocks to retinal afferents applied at the optic chiasm (OX) and optic tract (OT) in postsynaptic cells as a function of age, involving X-, Y-, and W-fibers. At four through six weeks postnatally the reduction in latency was found to be due to enhanced signal transmission at the axonal terminal region. Latency reduction continued after six weeks of life due to sharp increases in conduction velocity of the afferent fibers. Different steps in the maturation of visual response specifity were found for neurons of different functional types. Possible relationships are discussed between the development of neuronal responses of pretectal cells and the maturation of oculomotor behavior.


Influence of soil zinc concentrations on zinc sensitivity and functional diversity of microbial communities.
Pollution induced community tolerance (PICT) is based on the phenomenon that toxic effects reduce survival of the most sensitive organisms, thus increasing community tolerance. Community tolerance for a contaminant is thus a strong indicator for the presence of that contaminant at the level of adverse concentrations. Here we assessed PICT in 11 soils contaminated with zinc runoff from galvanised electricity pylons and 11 reference soils sampled at 10 m distance from these pylons. Using PICT, the influence of background concentration and bioavailability of zinc on zinc sensitivity and functional diversity of microbial communities was assessed. Zinc sensitivity of microbial communities decreased significantly with increasing zinc concentrations in pore water and calcium chloride extracted fraction while no significant relationship was found with total zinc concentration in the soil. It was also found that functional diversity of microbial communities decreased with increasing zinc concentrations, indicating that increased tolerance is indeed an undesirable phenomenon when environmental quality is considered. The hypothesis that zinc sensitivity of microbial communities is related to background zinc concentration in pore water could not be confirmed.


Neuroendocrine and behavioral development during puberty: a tale of two axes.
Puberty is marked by dramatic changes in neuroendocrine function. These changes have profound effects on the structure and function of the maturing nervous system, resulting in altered physiological and behavioral potentials in the adult organism. Indeed, the changes in neurobehavioral development during puberty rival those occurring during neonatal development. This review discusses the pubertal maturation of the hypothalamic-pituitary-gonadal and hypothalamic-pituitary-adrenal axes; specifically, how the pubertal rise in gonadal hormones influences the development of various steroid-dependent motivated behaviors in adulthood, as well as the differences in stress reactivity in prepubertal and adult animals. We conclude that puberty represents another significant and perhaps critical period of neurobehavioral development. Furthermore, we suggest that perturbations of the developing nervous system during this period of maturation may result in deleterious outcomes in the future physiological and behavioral function of an individual on reaching adulthood.


Optimization of the extraction condition for benzyl isothiocyanate contents in Salvadora persica roots "Siwak".
Benzyl isothocyanate is the major active antibacterial metabolite in Salvadora persica roots "Siwak" beside two minor isothiocyanate derivatives namely; 3-methoxy benzyl isothiocyanate and 3-hydroxy benzyl isothiocyanate. The extraction condition effect on the amount of benzyl isothiocyanate was explored in detailed study. Both cold and hot extraction with different solvents was applied. The amount of benzyl isothiocyanate was estimated using HPLC and HPTLC. The results indicated that cold extraction of the fresh samples with chloroform offers the maximum amount of benzyl isothiocyanate. Drying process leads to great loss of the active component of Siwak.


Lowering employee health care costs through the Healthy Lifestyle Incentive Program.
To evaluate the impact of the Healthy Lifestyle Incentive Program (HLIP), a worksite health program, on lowering prescription drug and medical costs. Health care cost data for Salt Lake County employees during 2004 through 2008 were linked with HLIP enrollment status. Additional program information was obtained from a cross-sectional survey administered in 2008. The program includes free annual screenings, tailored feedback on screening results, financial incentives for maintaining and modifying certain behaviors, and periodic educational programs and promotions to raise awareness of health topics. Frequency and cost of prescription drug and medical claims. Participation increased from 16% to 23% in men and 34% to 45% in women over the 5-year study period and was associated with a significantly greater level of physical activity and improved general health. Participants were generally satisfied with the HLIP (43% were very satisfied, 51% satisfied, 5% dissatisfied, and 1% very dissatisfied). The primary factors contributing to participation were financial incentives (more so among younger employees), followed by a desire to improve health (more so among older employees). Over the study period, the cost savings in lower prescription drug and medical costs was $3,568,837. For every dollar spent on the HLIP the county saved $3.85. Financial incentives and then a desire for better health were the primary reasons for participation. The HLIP resulted in substantial health care cost savings for Salt Lake County Government.


RNA demethylase ALKBH5 in cancer: from mechanisms to therapeutic potential.
RNA demethylase ALKBH5 takes part in the modulation of N6-methyladenosine (m6A) modification and controls various cell processes. ALKBH5-mediated m6A demethylation regulates gene expression by affecting multiple events in RNA metabolism, e.g., pre-mRNA processing, mRNA decay and translation. Mounting evidence shows that ALKBH5 plays critical roles in a variety of human malignancies, mostly via post-transcriptional regulation of oncogenes or tumor suppressors in an m6A-dependent manner. Meanwhile, increasing non-coding RNAs are recognized as functional targets of ALKBH5 in cancers. Here we reviewed up-to-date findings about the pathological roles of ALKBH5 in cancer, the molecular mechanisms by which it exerts its functions, as well as the underlying mechanism of its dysregulation. We also discussed the therapeutic implications of targeting ALKBH5 in cancer and potential ALKBH5-targeting strategies.


Precooling prevents overheating of subcutaneous fat in the use of RF capacitive heating.
The usefulness of precooling subcutaneous tissue in the hyperthermic treatment of deep-seated human tumors with capacitive application of radio-frequency (RF) was investigated. A capacitive hyperthermia unit operated at 8 MHz of radiofrequency was used to heat deep-seated human tumors. The electrode surfaces were covered with flexible vinyl sheets and the space between the electrode and the vinyl sheets perfused with 0.4% saline. The temperature of the saline was controlled by circulating the saline through built-in heat exchangers. The depth of heating was controlled by pairing electrodes of different diameters. When subcutaneous fat was less than 1 cm thick, various deep-seated tumors could be heated to a therapeutic temperature without significant discomfort in the subcutaneous tissue as long as the skin was properly cooled with the cold saline bolus. However, the same cooling method could not prevent the occurrence of pain in subcutaneous tissue in obese patients. The pain usually developed when the temperature of subcutaneous fat 1-2 cm below the skin surface exceeded 42 degrees C. We observed that cooling the human skin surface with 10 degrees C bolus for 20 min could substantially lower the temperature of fat as deep as 2.0-2.5 cm. Therefore, when the subcutaneous tissue was precooled with 10 degrees C saline for 20 min or longer before heating, it was possible to prevent successfully the overheating of subcutaneous fat as thick as 2.0-2.5 cm and to raise the temperature of deep-seated tumors to therapeutic levels.


Bidirectional relationship of problematic Internet use with hyperactivity/inattention and depressive symptoms in adolescents: a population-based cohort study.
Problematic Internet use (PIU), hyperactivity/inattention, and depressive symptoms are comorbid problems in adolescence, but the causal relationships among these issues are unclear. To assess the relationships among PIU, hyperactivity/inattention, and depressive symptoms in adolescents in the general population. This longitudinal cohort study used data from the Tokyo Teen Cohort study in Tokyo, Japan, for two years between October 2012 and January 2015. Of the 3171 pairs of children and parents, 3007 pairs continued to participate in the second wave of the Tokyo Teen Cohort study. A total of 3007 children were included in the analysis (mean [standard deviation] age, 9.7 [0.4] years; 1418 women [47.2%]. Cross-lagged panel analysis revealed that PIU at timepoint 1 was significantly associated with hyperactivity/inattention at timepoint 2 (β = 0.03; 95% confidence interval (CI) 0.01-0.06), and hyperactivity/inattention at timepoint 1 was also significantly associated with PIU at timepoint 2 (β = 0.07; 95% CI 0.04-0.10), even after adjustments were made for depressive symptoms. Furthermore, PIU at timepoint 1 was significantly associated with depressive symptoms at timepoint 2 (β = 0.05; 95% CI 0.01-0.12), and depressive symptoms at timepoint 1 were also significantly associated with PIU at timepoint 2 (β = 0.05; 95% CI 0.02-0.07), even after adjustments were made for hyperactivity/inattention. These results support the bidirectional relationships among PIU, hyperactivity/inattention, and depressive symptoms. PIU may be a target to improve hyperactivity/inattention and depressive symptoms in adolescents.


Site-selective monotitanation of dialkynylpyridines and its application for preparation of highly fluorescent pi-conjugated oligomers.
Reaction of Ti(O-i-Pr)(4)/2i-PrMgCl reagent with 2,n-bis[(trimethylsilyl)ethynyl]pyridines, where n is 3, 4, 5, and 6, or with 3,4-bis[(trimethylsilyl)ethynyl]pyridines, proceeded with excellent site-selectivity to afford the corresponding monotitanated complex. Synthetic application of the reaction was demonstrated by an efficient preparation of pi-conjugated oligomers having pyridine and enyne units alternately, which possess intense blue fluorescence emission.


Gene expression in snapbeans exposed to ozone and protected by ethylenediurea.
Ethylenediurea (EDU) is the most common chemical used to prevent ozone (O3) injury on vegetation. Despite considerable research, its mode of action remains elusive and gene expression has not been studied. Transcripts of major antioxidant enzymes (catalase, glutathione reductase, glutathione peroxidase) were measured for the first time in a model plant (Phaseolus vulgaris cv S156) after short-term O3 exposure (0 or 90 ppb, 5 h/d, 4 days) and a single spray with EDU (0 or 300 ppm). Visible, physiological and biochemical parameters were assessed as indices of O3-induced stress. In O3-exposed EDU-protected plants, levels of transcript, enzyme activity, H2O2 accumulation, gas exchange and foliar visible injury were similar to those in control plants. These results suggest that EDU may halt the O3-induced ROS generation within 24 h from the exposure, and thus the downstream cascade mechanisms leading to increased H2O2 production, impaired gas exchange, and occurrence of leaf lesions.


Face distinctiveness and delayed testing: differential effects on performance and confidence.
The author investigated the effect of delayed testing on participants' memory for distinctive and typical faces. Participants viewed distinctive and typical faces and were then tested for recognition immediately or after a delay of 3, 6, or 12 weeks. Consistent with prior research, analysis of measure of sensitivity (d') showed that participants performed better on distinctive rather than typical faces, and memory performance declined with longer retention intervals between study and testing. Furthermore, the superior performance on distinctive faces had vanished by the 12-week test. Contrary to d' data, however, an analysis of confidence scores indicated that participants were still significantly more confident on trials depicting distinctive faces, even with a 12-week delay between study and recognition testing.


Brazilian and French sensory perception of complex cosmetic formulations: a cross-cultural study.
Brazil and France are two major beauty markets worldwide. Despite this, there is not much cross-information on sensory analysis of cosmetic products between both population of these countries. The objective of this study was to compare the sensory perception of cosmetic formulations between Brazilian and French assessors and establish cross-culturally preferences. For this, a total panel of 100 consumers of cosmetics evaluated four different products. The same protocol for the sensory analysis was followed in both countries. The panellists were able to perceive differences in the products and the method proved to be repeatable in both countries. The presence of UV filters in the formulation was noticed and displeased both populations. Brazilians, although dissatisfied with the sensory aspect of the sunscreen, are willing to use it for its UV protection. This work delivers important information on the sensory perception of cosmetics by people from different countries and brings important knowledge to develop products with textural properties that will be appreciated worldwide.


Basal ganglia volume is strongly related to P3 event-related potential in premanifest Huntington's disease.
The P3 event-related potential (ERP) is presumably partly generated by the basal ganglia. Because degeneration of these brain structures starts many years before clinical disease onset in Huntington's disease (HD), studying the interplay between P3 characteristics and basal ganglia volumes in 'premanifest' carriers might lead to new insights into the disease process. Fourteen premanifest\ HD mutation carriers and twelve non-mutation carriers underwent clinical, MRI and P3-ERP investigations. The P3 was measured during the Sustained Attention to Response Task. P3 amplitude and latency did not differ between groups. In carriers, longer P3 latency during Go-trials was strongly associated with smaller caudate, putamen and globus pallidus volumes (r values up to -0.827, P ≤ 0.001). The exceptionally strong relations of P3 latency with basal ganglia volumes in carriers suggest that the P3 may provide a marker for disease progression in HD.


[Analysis of ooplasmic flows and their structural bases during cleavage inPimpla turionellae L. (Hymenoptera) : II. Strain of egg architecture by different acceleration gradients].
In the egg ofPimpla turionellae L., three density gradients are produced by different methods of centrifugation. In spinning, the egg is rotated about its own long axis, so that the lightest egg material is collected in a central column (radial stratification). Flinging parallel to the long axis has been carried out at a short distance from the rotational axis (rotation axis situated immediately adjacent to a long edge of the egg) as well as further from the rotational axis (at a distance of 4.5 cm). A transversal stratification is thereby produced, in which the lightest and the heaviest material are collected at opposite long edges of the egg. The same stratification results from all three methods. From centripetal outward toward centrifugal, a lipid zone, a light yolk zone, a cytoplasm zone poor in yolk granules (basophilic cytoplasmic network), a dense yolk zone and a glycogen zone are formed. The sharpness of separation between the zones in eggs centrifuged during maturation divisions is better than that in eggs spun or flung during cleavage or pre-blastoderm formation. Either development ceases soon after the experiment has taken place or the centrifuged eggs develop into larvae. Half of the eggs flung at short distance or spun about the rotational axis with 10000-12000g are able to develop into embryos. Eggs handled by both of these methods show identical development at increasing accelerations. Eggs flung at greater distance already cease their development after a treatment at 10000g. Malformations or incomplete embryos do not occur in any group of experiments. These findings allow postulation of a system of factors sensitive to accelerations higher than 10000g, which is arranged cylindrically within the egg and which is not connected in any way to the shiftable, light microscopic fractions. This postulated system of factors could have a dynamic function and thereby be an essential component of the primary organization pattern in the egg ofPimpla.Only eggs forming polar caps at opposite ends of the egg within 1.5-2 hours after the experiment will develop into embryos. The polar caps are formed independently of each other. Following too great a stress on the end of the egg oblique to the rotational axis, ooplasm contraction fails to take place. Ooplasmic redistribution has been pursued in life and in section pictures in eggs continuing to and failing to develop. Redistribution combined with a regulated removal of zones is evidently connected with the energid migration. The content of the lipid plasm zone disappears to some extent during redistribution. The posterior part possesses the highest capacity for development in nonviable eggs. It is sometimes able to form a blastoderm independently of the anterior region. A blastoderm is formed only if the posterior part includes the region between 25 and 35% of the egg.


Evaluation of Phytoremediation Potential of Pteris vittata L. on Arsenic Contaminated Soil Using Allium cepa Bioassay.
The present study assessed the utility of Allium cepa based cyto-genotoxicity bioassays in evaluating the arsenic toxicity and remediation potential of Pteris vittata on contaminated soil of Lakhimpur-Kheri district. Untreated and P. vittata treated soil extracts were used for cyto-genotoxicity tests in A. cepa. Results showed that P. vittata extracted high concentration of arsenic, which ranged from 220 to 1420 mgkg-1 in different soils. Cyto-genotoxic assessment of A. cepa showed that extract of P. vittata treated soil had lower cyto-genotoxic effects as compared to untreated soil. A higher mitotic index (10%) while lower mitotic depression (29%), relative abnormality rate (10%), chromosomal aberrations (1%) and micronuclei (2%) were detected in root meristematic cells of A. cepa exposed to remediated soil extract in comparison to untreated soil. The studies provide a simple, rapid and economic cyto-genotoxicity bioassay tool for evaluating toxicity of contaminated soils of contaminated soils as well as revealed the phytoremdiation property of P. vittata against arsenic toxicity.


Olfactory epithelium progenitors: insights from transgenic mice and in vitro biology.
The rodent olfactory epithelium (OE) is capable of prolonged neurogenesis, beginning at E10 in the embryo and continuing throughout adulthood. Significant progress has been made over the last 10 years in revealing the signals that drive induction, differentiation and survival of its Olfactory Receptor Neurons (ORNs). Our understanding of the identity of specific progenitors or precursors that respond to these signals is, however, less well developed, and the search is still on for the elusive, definitive multipotent neuro-glial OE "Stem cell". Here, we review several lines of evidence that support the existence of a heterogeneous population of neural and glial progenitors in the olfactory mucosa, and highlight the differences in the identity and activity of progenitors found in the embryonic and adult OE. In particular, we show how recent advances in mouse transgenesis, and in the development of in vitro assays of progenitor activity, have helped to demonstrate the existence of multiple classes of olfactory mucosa-based progenitors.


Manipulating exchange bias in 2D magnetic heterojunction for high-performance robust memory applications.
The exchange bias (EB) effect plays an undisputed role in the development of highly sensitive, robust, and high-density spintronic devices in magnetic data storage. However, the weak EB field, low blocking temperature, as well as the lack of modulation methods, seriously limit the application of EB in van der Waals (vdW) spintronic devices. Here, we utilized pressure engineering to tune the vdW spacing of the two-dimensional (2D) FePSe3/Fe3GeTe2 heterostructures. The EB field (HEB, from 29.2 mT to 111.2 mT) and blocking temperature (Tb, from 20 K to 110 K) are significantly enhanced, and a highly sensitive and robust spin valve is demonstrated. Interestingly, this enhancement of the EB effect was extended to exposed Fe3GeTe2, due to the single-domain nature of Fe3GeTe2. Our findings provide opportunities for the producing, exploring, and tuning of magnetic vdW heterostructures with strong interlayer coupling, thereby enabling customized 2D spintronic devices in the future.


Filtration of chylomicrons by the liver may influence cholesterol metabolism and atherosclerosis.
A fenestrated endothelial lining of sinusoids in rat liver has been shown to separate chylomicrons of different sizes following their injection into the portal vein. This sieving may have physiological importance, since during low dietary fat intake some intestinal lipoproteins are probably small enough to contact liver cells, but during high dietary fat loads most chylomicrons are too large to pass through the filter and must first be degraded to smaller remnants. The liver plays a central role in cholesterol metabolism since it catabolises dietary cholesterol which inhibits synthesis of cholesterol to be circulated as liver-derived very low density lipoproteins (VLDL) and low density lipoproteins. The sieving of chylomicrons, remnants and other lipoproteins by the sinusoidal endothelium of the liver may thus play an important role in lipid transport, affecting the balance of various lipoprotein moieties which in turn may affect the relationship of dietary lipids to various hyperlipidaemias and atherosclerosis.


Diagnosis and Treatment of the Causes of Chronic Pelvic Pain
Ten years of clinical evaluations of women with chronic pelvic pain resulted in concern that diagnostic laparoscopic surgery is performed too frequently in these patients. Of 500 women, the pain was due to urologic, myofascial, musculoskeletal, gastrointestinal, or psychologic causes in 30%, rather than to disorders of the reproductive organs. Laparoscopy would be inappropriate in these patients. By providing women with appropriate therapy of nongynecologic pain, those whose pain is due to gynecologic sources can be treated more appropriately. In approximately 70% of these latter patients, endometriosis is the primary finding. A paradigm for the diagnosis and the cost-effective treatment of women with chronic pelvic pain of gynecologic cause was developed.


Fin sweep angle does not determine flapping propulsive performance.
The importance of the leading-edge sweep angle of propulsive surfaces used by unsteady swimming and flying animals has been an issue of debate for many years, spurring studies in biology, engineering, and robotics with mixed conclusions. In this work, we provide results from three-dimensional simulations on single-planform finite foils undergoing tail-like (pitch-heave) and flipper-like (twist-roll) kinematics for a range of sweep angles covering a substantial portion of animals while carefully controlling all other parameters. Our primary finding is the negligible 0.043 maximum correlation between the sweep angle and the propulsive force and power for both tail-like and flipper-like motions. This indicates that fish tails and mammal flukes with similar range and size can have a large range of potential sweep angles without significant negative propulsive impact. Although there is a slight benefit to avoiding large sweep angles, this is easily compensated by adjusting the fin's motion parameters such as flapping frequency, amplitude and maximum angle of attack to gain higher thrust and efficiency.


Predictors of clinical performance among internal medicine residents.
To determine whether personal characteristics influence residents' psychological states during training and to evaluate the relative importance of personal characteristics and psychological states in predicting clinical performance. Cohort study utilizing prospective, serial surveys of emotions (anxiety, depression, competence) and attitudes (satisfaction with the decision to become a physician) among two classes of internal medicine residents during all years of their training. Subjects completed a socio-demographic survey at the conclusion of training, and faculty-assigned clinical ranks and examination scores were used to rate their clinical performances. Personal characteristics had a stronger relationship to psychological states during the first training year than in subsequent years. The highest association was found for depression, for which 25% of the variation was accounted for by personal characteristics. The combination of personal characteristics and psychological states explained 48% of the variation in clinical ranks and 38% of the variation in American Board of Internal Medicine certifying examination scores. There are recognizable relationships among the personal characteristics of residents, their psychologic states during training, and their clinical performances. These results should be helpful to program directors and faculty in identifying potentially weak residents and avoiding pitfalls when working with troubled residents.


Taste-guided isolation of sweet-tasting compounds from grape seeds, structural elucidation and identification in wines.
This work aimed at improving knowledge about sweetness in dry wines. Following on from the empirical observations of winegrowers, we assessed the contribution of grape seeds to wine sensory properties. An inductive fractionation method guided by gustatometry was used to isolate and characterize sweet-tasting compounds from grapes. Fractionation of grape seed macerates was achieved by liquid-liquid extraction, centrifugal partition chromatography (CPC) and preparative HPLC. Then, the structures of the purified compounds were elucidated by use of FTMS and NMR. Five compounds were identified: two new compounds, 2-hydroxy-3-methylpentanoic-2-O-β-glucopyranoside (H3MP-G) and 2-hydroxy-4-methylpentanoic-2-O-β-glucopyranoside acids (H4MP-G), along with gallic-4-O-β-glucopyranoside acid (AG-G), 3-indolyl-(2R)-O-β-d-glycoside lactic acid (ILA-G) and epi-DPA-3'-O-β-glucopyranoside acid (epi-DPA-G). These compounds exhibited various levels of sweetness in a hydro-ethanolic solution and in white and red wines. Additionally, H3MP-G, H4MP-G and epi-DPA-G were identified for the first time in grapes and wines, whereas AG-G has already been reported in white grapes but never in wine.


Students together with academics ensures retention and success: The STARS project.
Approximately 23% of Australian undergraduate students who commenced a degree in 2018 will not complete their program of study. Of these students, approximately 25% cite their 'study is too hard' or 'too much' when withdrawing from their degree. Research has identified that the most common group of students to struggle with completing their program of study are those from equity groups. This paper explores a support strategy aimed at improving the first-year student experience and progression rates. A proof of concept project was undertaken to explore undergraduate midwifery students' experiences of an Expectation Led Planned Organisational teaching strategy into a course. The study was undertaken at two sites of a regional University in New South Wales, Australia. All students (n42) enrolled in a core course, in the first year of a Bachelor of Midwifery program. A mixed methods approach was used. Quantitative data was collected through the university's program and course management systems and analysed using descriptive statistics to find patterns. Qualitative data were collected via a focus group to provide greater knowledge of the acceptability of the strategy and analysed using content analysis. The inclusion of sequenced email reminders for upcoming assessment tasks was valued by students. There were greater retention and progression rates and a shift in the grade distribution towards higher course grades overall. Student satisfaction with learning activities increased along with course assessment satisfaction. Student engagement in learning is enhanced and retention and success rates are increased when academics use technology in a student focused manner. Further research is required to further explore and evaluate strategies that are student focused and acceptable as well as sustainable for the higher education context.


A Coomassie blue-binding assay for the microquantitation of immobilized proteins.
A sensitive assay procedure for the determination of microgram quantities of immobilized proteins is described. The procedure is based on the property of Coomassie blue G-250 to bind strongly yet reversibly to proteins. The assay involves incubation of the immobilized protein with a solution containing 0.1% Coomassie blue, 10% acetic acid, and 25% isopropyl alcohol in distilled water at room temperature followed by washing off of the unbound dye. The protein-bound dye is eluted with methanolic NaOH, acidified, and the absorbance is measured at 605 nm. The assay is highly reproducible and several proteins immobilized on various matrices could be conveniently assayed. Protein values determined by the dye-binding assay showed good agreement with those obtained by other procedures.


Blind nasotracheal intubation.
One hundred fifty successive nonapneic patients requiring tracheal intubation had blind nasotracheal intubation performed. The primary indications for intubation were: drug overdose, 54 (36%); head injury, 36 (24%); COPD, 18 (12%); cerebrovascular accident, 15 (10%); congestive heart failure, 11 (7%); and other, 16 (11%). One hundred thirty-eight patients (92%) were successfully intubated using this technique.


Statistical file matching of flow cytometry data.
Flow cytometry is a technology that rapidly measures antigen-based markers associated to cells in a cell population. Although analysis of flow cytometry data has traditionally considered one or two markers at a time, there has been increasing interest in multidimensional analysis. However, flow cytometers are limited in the number of markers they can jointly observe, which is typically a fraction of the number of markers of interest. For this reason, practitioners often perform multiple assays based on different, overlapping combinations of markers. In this paper, we address the challenge of imputing the high-dimensional jointly distributed values of marker attributes based on overlapping marginal observations. We show that simple nearest neighbor based imputation can lead to spurious subpopulations in the imputed data and introduce an alternative approach based on nearest neighbor imputation restricted to a cell's subpopulation. This requires us to perform clustering with missing data, which we address with a mixture model approach and novel EM algorithm. Since mixture model fitting may be ill-posed in this context, we also develop techniques to initialize the EM algorithm using domain knowledge. We demonstrate our approach on real flow cytometry data.


Pretransplant gastroesophageal reflux compromises early outcomes after lung transplantation.
Gastroesophageal reflux disease (GERD) is implicated as a risk factor for bronchiolitis obliterans syndrome after lung transplantation, but its effects on acute rejection, early allograft function, and survival are unclear. Therefore, we sought to systematically understand the time-related impact of pretransplant GERD on graft function (spirometry), mortality, and acute rejection early after lung transplantation. From January 2005 to July 2008, 215 patients underwent lung transplantation; 114 had preoperative pH testing, and 32 (28%) had objective evidence of GERD. Lung function was assessed by forced 1-second expiratory volume (FEV(1); percent of predicted) in 97 patients, mortality by follow-up (median, 2.2 years), and acute rejection by transbronchial biopsy. Pretransplant GERD was associated with decreased FEV(1) early after lung transplantation (P = .01) such that by 18 months, FEV(1) was 70% of predicted in double lung transplant patients with GERD versus 83% among non-GERD patients (P = .05). A similar decrease was observed in single lung transplantation (50% vs 60%, respectively; P = .09). GERD patients had lower survival early after transplant ( P = .02)-75% versus 90%. Presence of GERD did not affect acute rejection (P = .6). For lung transplant recipients, pretransplant GERD is associated with worse early allograft function and survival, but not increased acute rejection. The compromise in lung function is substantial, such that FEV(1) after double lung transplant in GERD patients approaches that of single lung transplant in non-GERD patients. We advocate thorough testing for GERD before lung transplantation; if identified, aggressive therapy early after transplant, including fundoplication, may prove efficacious.


Meta-analysis of prophylactic antibiotic use in acute necrotizing pancreatitis.
Death from infected necrosis in acute pancreatitis is common and prevention has focused on prophylactic antibiotics. This study assesses whether intravenous prophylactic antibiotic use reduces infected necrosis and death in acute necrotizing pancreatitis. A meta-analysis of randomized controlled trials was carried out. Medline, Web of Science, the Cochrane controlled trials register and international conference proceedings were searched, with a citation review of relevant primary and review articles. Six of 328 studies assessed were included in data extraction. Primary outcome measures were infected necrosis and death. Secondary outcome measures were non-pancreatic infections, surgical intervention and length of hospital stay. Prophylactic antibiotic use was not associated with a statistically significant reduction in infected necrosis (relative risk (RR) 0.77 (95 per cent confidence interval (c.i.) 0.54 to 1.12); P = 0.173), mortality (RR 0.78 (95 per cent c.i. 0.44 to 1.39); P = 0.404), non-pancreatic infections (RR 0.71 (95 per cent c.i. 0.32 to 1.58); P = 0.402) and surgical intervention (RR 0.78 (95 per cent c.i. 0.55 to 1.11); P = 0.167). It was, however, associated with a statistically significant reduction in hospital stay (P = 0.040). Prophylactic antibiotics do not prevent infected necrosis or death in acute necrotizing pancreatitis.


Diminished visualization of renal outlines in adult renal polycystic disease.
Nephrotomographic and angiographic features of adult polycystic kidney disease (Potter type 3) are well documented, although comments on plain film findings are scant. In 34 patients with adult polycystic kidney disease, we found non-visualization of 75% or more of the renal outlines on the abdominal plain film. This finding should raise the possibility of underlying polycystic disease.


Relationship between Patient Age and Disease Features in a Prospective Cohort of 1560 Women Affected by Endometriosis.
To assess the relationship between age, location of the disease, and surgical procedures performed in patients undergoing surgical management of endometriosis. Retrospective study using data prospectively recorded in the North-West Inter Regional Female Cohort for Patients with Endometriosis database. University tertiary referral center. Women who underwent surgical management of symptomatic endometriosis between April 2009 and April 2014. Patients were allocated to 6 groups according to their age at the time of surgery: ≤20, 21 to 25, 26 to 30, 31 to 35, 36 to 40 and >40 years. Patient characteristics, prior history, location of endometriotic lesions, stage of disease, intraoperative findings, and surgical procedures were retrieved from a prospectively recorded database. Patient characteristics, symptoms, location of endometriosis, and type of surgery performed were compared between groups. In total, 1560 procedures were performed. Of these, more than one-half were carried out in women between the age of 26 to 35 years and the majority were performed in women aged between 26 and 30 years. Only 2% of procedures were performed in women under the age of 20 years. The mean stage of the disease at the time of surgical diagnosis was stage II for women younger than 20 years, stage III for those in the age group of 21 to 25 years, and stage IV for those older than 26 years. The rate of diagnosis of deep colorectal nodules increased progressively from 20 to 26 years and remained stable thereafter. Our data confirm that endometriosis is a disease that probably progresses from adolescence until the adult period when symptoms (pain or infertility) become debilitating and require surgery. Our data suggest that policies relating to the prevention and early diagnosis of endometriosis should focus on women younger than 25 years.


3-Monochloropropane-1,2-diol causes spermatogenesis failure in male rats via Sertoli cell dysfunction but not testosterone reduction.
3-Monochloropane-1,2-diol (3-MCPD), a common food contaminant, has been confirmed to impair male fertility, but the mechanism has not been fully clarified. This study systematically explored the spermatogenesis impairment induced by 3-MCPD in vivo and in vitro with a focus on Sertoli cells (SCs) and spermatogonial stem cells (SSCs). After adult male Sprague-Dawley rats were administered 36 and 72 mg/kg b.w./day 3-MCPD daily for 4 weeks, the total sperm concentration dramatically decreased by 28.9 % and 57.7 %, respectively, and obvious testicular seminiferous tubule atrophy was observed. 3-MPCD exposure decreased serum testosterone levels but not intratesticular testosterone levels and upregulated the expression of steroidogenesis enzymes in both rat testes and primary Leydig cells. 3-MCPD did not reduce the number and self-renewal marker PLZF+ of SSCs; however, it downregulated the key meiotic genes Stra8 and Rec8 in the rat testis but not in primary germ cells. Although SC counts were not affected, 3-MCPD downregulated androgen receptor (AR) in rat testes and primary SCs. In addition, 3-MCPD downregulated p-CREB (transcription factor of AR), paracrine meiosis regulators Nrg1 and Nrg3 and retinoic acid synthetase Aldh1a1 in primary SCs. In summary, 3-MCPD caused impairment of spermatogenesis by inhibiting secretion of meiosis regulators and disturbing testosterone signalling in SCs.


A longitudinal study of psychological and social factors affecting recovery from psychiatric breakdowns.
Thirty-five people who had suffered a recent onset of symptoms of depression and/or anxiety were interviewed soon after being seen by a clinician, and again six months later. Symptom scores at the second interview were predicted by whether any plans subjects had formed by the first interview had gone wrong, by major non-health difficulties, and by internal, stable and global attributions made at the first interview about the event or difficulty that was most distressing before symptoms became severe.


Individual and Environmental Factors Affecting Adaptive Behavior of Toddlers with Autism Spectrum Disorder: Role of Parents' Socio-cultural Level.
The effects of environmental factors [including Socio-Economic Status, Cultural Capital, and Social Capital (Socio-Cultural Level) of both parents] on the Vineland-II adaptive behavior dimensions of toddlers with autism spectrum disorder (ASD), in addition to individual factors, was investigated in 148 Italian toddlers (82% males), aged 18 to 37 months with ASD. Toddlers' age and Griffiths Mental Development Scales general development affected all of the adaptive behavior dimensions, with negative and positive associations, respectively. The Child Behavior Checklist comorbid conditions were negatively associated with some adaptive behavior dimensions while the ADOS-2 Social affect only with the communication dimension. Mothers' and fathers' specific Socio-Cultural Level dimensions were positively associated with toddlers' specific adaptive behavior dimensions with the same magnitude as comorbid conditions.


"I am an air quality scientist"- Using citizen science to characterise school children's exposure to air pollution.
Children are particularly vulnerable to the harmful effects of air pollution. To tackle this issue and implement effective strategies to reduce child exposure, it is important to understand how children are exposed to this risk. This study followed a citizen science approach to air pollution monitoring, aiming to characterise school children's exposure to air pollution and to analyse how a citizen science approach to data collection could contribute to and enhance the research process. 258 children across five London primary schools attended air pollution education sessions and measured air pollution for a week using backpacks with built-in air quality sensors. Children received a summary of the results, advice and information on how to reduce exposure to air pollution. Data on the impact of the approach on the school community were collected using surveys and focus groups with children and their parents and interviews with the teachers involved. The unique data set obtained permitted us to map different routes and modes of transport used by the children and quantify different exposure levels. We identified that, on average, children were exposed to higher levels of air pollution when travelling to and from school, particularly during the morning journey where air pollution levels were on average 52% higher than exposures at school. Children who walked to and from school through busy main roads were exposed to 33% higher levels of air pollution than those who travelled through back streets. The findings from this study showed that using a citizen science approach to data collection, where children are actively involved in the research process, not only facilitated the gathering of a large data set by encouraging participation and stimulating adherence with the study protocol, but also increased children's awareness of air pollution, encouraging them to adopt positive behaviour changes to reduce their exposure.


Detect the early-warning signals of diseases based on signaling pathway perturbations on a single sample.
During the pathogenesisof complex diseases, a sudden health deterioration will occur as results of the cumulative effect of various internal or external factors. The prediction of an early warning signal (pre-disease state) before such deterioration is very important in clinical practice, especially for a single sample. The single-sample landscape entropy (SLE) was proposed to tackle this issue. However, the PPI used in SLE was lack of definite biological meanings. Besides, the calculation of multiple correlations based on limited reference samples in SLE is time-consuming and suspect. Abnormal signals generally exert their effect through the static definite biological functions in signaling pathways across the development of diseases. Thus, it is a natural way to study the propagation of the early-warning signals based on the signaling pathways in the KEGG database. In this paper, we propose a signaling perturbation method named SSP, to study the early-warning signal in signaling pathways for single dynamic time-series data. Results in three real datasets including the influenza virus infection, lung adenocarcinoma, and acute lung injury show that the proposed SSP outperformed the SLE. Moreover, the early-warning signal can be detected by one important signaling pathway PI3K-Akt. These results all indicate that the static model in pathways could simplify the detection of the early-warning signals.


Toxicity and mortality of cytoreduction and intraoperative hyperthermic intraperitoneal chemotherapy in pseudomyxoma peritonei--a report of 103 procedures.
To report on treatment related toxicity and mortality in patients with pseudomyxoma peritonei (PMP) treated by cytoreduction in combination with intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) and to identify prognostic factors. A review was performed of 103 procedures of cytoreduction and intraoperative HIPEC for PMP between 1996 and 2004. Toxicity was graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) classification. A surgical complication was defined as any post-operative event that needed re-intervention. Pre and peroperative factors were studied on their relationship to toxicity and mortality. The median hospital stay was 21 days (4-149) with a treatment related toxicity of 54% and a 30 days mortality of 3%. In univariate analysis, toxicity was associated with abdominal tumour load (p<0.01), completeness of cytoreduction (p<0.01), and age (p=0.05). Surgical complications, mainly small bowel perforations/suture leaks, were the main cause of toxicity. A favourable pathology decreased mortality. Cytoreduction in combination with intraoperative HIPEC in PMP patients is a treatment with a relatively high toxicity, but a considerable long-term survival in selected patients. Toxicity is mainly surgery related. Concentration of cases to acquire sufficient experience and better selection on age, pathology, and extent of disease is essential to reduce treatment related toxicity and mortality.


Respiratory and peripheral muscular ultrasound characteristics in ICU COVID 19 ARDS patients.
Severe cases of coronavirus disease 2019 develop ARDS requiring admission to the ICU. This study aimed to investigate the ultrasound characteristics of respiratory and peripheral muscles of patients affected by COVID19 who require mechanical ventilation. This is a prospective observational study. We performed muscle ultrasound at the admission of ICU in 32 intubated patients with ARDS COVID19. The ultrasound was comprehensive of thickness and echogenicity of both parasternal intercostal and diaphragm muscles, and cross-sectional area and echogenicity of the rectus femoris. Patients who survived showed a significantly lower echogenicity score as compared with those who did not survive for both parasternal intercostal muscles. Similarly, the diaphragmatic echogenicity was significantly different between alive or dead patients. There was a significant correlation between right parasternal intercostal or diaphragm echogenicity and the cumulative fluid balance and urine protein output. Similar results were detected for rectus femoris echogenicity. The early changes detected by echogenicity ultrasound suggest a potential benefit of proactive early therapies designed to preserve respiratory and peripheral muscle architecture to reduce days on MV, although what constitutes a clinically significant change in muscle echogenicity remains unknown.


[Toxoplasma gondii pneumopathy in a patient with the acquired immunodeficiency syndrome: demonstration of the parasite by bronchioloalveolar lavage].
Toxoplasmosis is an infection frequently observed in patients with acquired immunodeficiency syndrome. Its first manifestations usually are cerebromeningal symptoms, but others may occur. A pulmonary lesion is sometimes present; it is discovered at post-mortem examination in most cases. The authors report a case of pulmonary toxoplasmosis diagnosed by bronchoalveolar lavage (BAL). Three points are emphasized: toxoplasmosis of the lung may produce an interstitial pneumonia similar to that of pneumocystosis; diagnosis can be made non-invasively by BAL, and provided an appropriate treatment is administered, the outcome may be favourable.


Multi-domain cognitive impairments at school age in very preterm-born children compared to term-born peers.
Preterm infants are at risk for functional impairments in motor, cognitive, and behavioral development that may persist into childhood. The aim of this study was to determine the co-occurrence of cognitive impairments in multiple cognitive domains at school age in very preterm born children compared to term-born children. Comparative study including 60 very preterm-born children (gestational age ≤ 32 weeks) and 120 term-born controls. At school age, we assessed intelligence with the WISC-III, and visuomotor integration with the NEPSY-II, verbal memory with the AVLT, attention with the TEA-ch, and executive functioning with the BRIEF. We investigated co-occurrence of various abnormal (<5th percentile) and suspect-abnormal (<15th percentile, including both suspect and abnormal) cognitive functions. At mean age 8.8 years, 15% of preterm children had abnormal outcomes in multiple cognitive functions (≥2), versus 3% of the controls (odds ratio, OR 4.65, 95%-confidence interval, CI 1.33-16.35). For multiple suspect-abnormal cognitive outcomes, rates were 55% versus 25% (OR 3.02, 95%-CI 1.49-6.12). We found no pattern of co-occurrence of cognitive impairments among preterm children that deviated from term-born controls. However, low performance IQ was more frequently accompanied by additional cognitive impairments in preterms than in controls (OR 5.43, 95%-CI 1.75-16.81). A majority of preterm children showed co-occurrence of impairments in multiple cognitive domains, but with no specific pattern of impairments. The occurrence of multi-domain cognitive impairments is higher in preterms but this seems to reflect a general increase, not one with a pattern specific for preterm-born children.


Assessment of pesticides in water using time-weighted average calibration of passive sampling device manufactured with carbon nanomaterial coating on stainless steel wire.
The continued contamination of water sources by pesticides is a problem that involves the life of aquatic organisms and human health, especially in countries whose economy is based on agriculture. The need to know the quality of drinking water under these circumstances is a priority for the public health of any community. Passive sampling methods allow the determination of long-term environmental pollutants through a single sample collection, reducing time and cost of analyses. One advantage of passive sampling is that it is possible to calculate a time-weighted average (TWA) concentration value or an equilibrium concentration value, depending on the type of device used and the exposure time. Passive sampling techniques using carbon nanomaterials (CNMs) have a high potential for pesticide sampling in aquatic systems. A device for passive sampling manufactured with CNMs in a microextraction system and recyclable materials was calibrated in laboratory exposure conditions over 15 days. The calibration results showed linear accumulation periods between 5 and 10 days. Sampling rates were between 0.014 and 0.146 mL day-1. The sampler was field-tested in the San Francisco river basin in the state of Minas Gerais in Brazil for 7 days. This research allowed for the detection and calculation of TWA concentrations for organochlorine pesticides such as α-HCH, 4,4-DDE, and 4,4-DD in water sources. The manufactured device demonstrated greater sensitivity than the grab sampling processes for the detection of pesticides. The performed passive sampling system using gas chromatography/mass spectrometry (GC/MS) technique allowed for the collection, detection, identification, and quantification of 26 pesticides.


One-Shot Generation of Epitope-Directed Monoclonal Antibodies to Multiple Nonoverlapping Targets: Peptide Selection, Antigen Preparation, and Epitope Mapping.
This chapter describes an epitope-directed approach to generate antipeptide monoclonal antibodies to multiple nonoverlapping protein sites using a cocktail of fusion peptides as immunogen. It provides a step-by-step protocol on how antigenic peptides on a target protein can be identified by in silico prediction and discusses considerations for final peptide selection. Each antigenic peptide (10-20 amino acids long) is displayed as three-copy inserts on the surface exposed loop of a thioredoxin scaffold protein. The corresponding DNA coding sequence specifying the tripeptide insert flanked by Gly-Ser-Gly-Ser-Gly linkers is cloned in-frame into the Rsr II site of the thioredoxin gene in the pET-32a vector. The presence of a C-terminal polyhistidine tag (His6-tag) allows the soluble fusion proteins to be purified by one-step native immobilized metal affinity chromatography (IMAC) to greater than 95% purity. Multiple thioredoxin fusion proteins are mixed in equimolar concentrations and used as an immunogen cocktail for animal immunization. The use of short antigenic peptides of known sequence facilitates direct epitope mapping requiring only small mutagenesis scan peptide libraries in the multipin peptide format.


The acute and short-time effect of supplementation with the combination of n-3 fatty acids and acetylsalicylic acid on platelet function and plasma lipids.
Antiplatelet therapy with acetylsalicylic acid (ASA) is commonly used to reduce the risk of cardio- and cerebrovascular events. Fish consumption has been inversely related to coronary disease, which has been partly attributed to an inhibitory effect of n-3 polyunsaturated fatty acids (n-3 PUFA) on platelet production of tromboxane A2. In this study, we investigated the acute and short-time effect of supplementation with n-3 PUFA and intravenous ASA on platelet function, platelet fatty acid composition and plasma lipids. Eighteen healthy men were randomly allocated to a daily intake of 10 g n-3 PUFA or placebo. After this supplement (14 h and 14 days), blood was sampled before and after intravenous injection of 100 mg ASA. n-3 PUFA given for 14 days caused a minor inhibition of platelet reactivity but negligible compared to 100 mg ASA. No additive effect of n-3 PUFA and ASA could be demonstrated.


Prediction of acute graft-versus-host disease and detection of distinct end-organ targets by enumeration of peripheral blood cytokine spot-forming cells.
Acute graft-versus-host disease (aGVHD) remains a significant cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation. It was hypothesized that type 1 cytokines promoted aGVHD and type 2 cytokines inhibited it. However, recent publications demonstrated contradictory results in murine models. Type 1/2 paradigm in aGVHD remains to be determined in human. Using enzyme-linked immunospot assay that reflects ongoing immune status in vivo, we measured spot-forming cells (SFCs) for interferon (IFN)-gamma, interleukin (IL)-12, IL-4, and IL-10 in peripheral blood from 56 patients with hematological disorders who underwent allogeneic hematopoietic stem cell transplantation. The numbers of IFN-gamma and IL-4 SFCs in patients with grade II approximately IV aGVHD were significantly higher than those in patients with grade 0 approximately I aGVHD. The enumeration of cytokine SFCs predicted aGVHD approximately 4 days before it became clinically evident, since IFN-gamma SFCs in asymptomatic phase that later progressed into grade II approximately IV aGVHD were elevated in 8 out of 8 evaluable patients. Similarly, IL-4 SFCs were elevated in 6 of 8 patients. In addition, Type 1 cytokine SFCs contributed to the intestinal, but not skin and hepatic aGVHD. Enzyme-linked immunospot assay is clinically useful for predicting aGVHD and detecting distinct end-organ targets following allogeneic hematopoietic stem cell transplantation.


Congenital varicella syndrome.
The authors are reporting a typical case of congenital varicella syndrome following maternal varicella during the 17th week of pregnancy. At birth, the newborn showed necrotic bullae on the skin that healed later with characteristic scars. Other typical anomalies, i.e. hypoplastic limbs with muscular atrophy and clubfoot, intrauterine atrophy, dysphagia and anisocoria were also found. In view of the risk of serious malformations following intrauterine varicella infection attempts should be made to prevent varicella zoster virus infection during pregnancy.


Effect of high-intensity interval training on obstructive sleep apnea severity: A randomized controlled trial.
Vigorous physical activity has been associated with a reduced risk of developing obstructive sleep apnea (OSA). However, whether high-intensity interval training (HIIT) reduces OSA severity remains unclear. Thus, this study aimed to investigate the impact of 12 weeks of HIIT on the apnea-hypopnea index (AHI) and sleep parameters in participants with moderate-severe OSA. In this randomized controlled trial, 36 adults (19 males; 52.2 ± 9.8 years; body mass index = 34.2 ± 5.8) with moderate to severe OSA (AHI = 42.0 ± 22.9 e/h) were randomly assigned to HIIT [5 periods of 4 min of walking or running on a treadmill at 90-95 % of maximum heart rate (HRmax) interspersed with 3 min of walking at 50-55 % of HRmax performed three times per week for 12 weeks] or a control group (CG; stretching exercises performed two times per week for 12 weeks). Sleep parameters were assessed at baseline and after 12 weeks through overnight polysomnography. Generalized estimated equations assessed differences between groups over time. There was not group × time interaction for body mass index between groups (p = 0.074). However, significant group × time interactions were observed for AHI (CG change = 8.2 ± 3.7, HIIT change = -8.6 ± 4.8; p = 0.005), SaO2 minimum (CG change = -1.6 ± 1.6 %, HIIT change = 0.4 ± 2.3 %; p = 0.030), total sleep time (CG change = -31.5 ± 19.5 min, HIIT change = 33.7 ± 19.3 min; p = 0.049), and sleep efficiency (CG change = -3.2 ± 4.4 %, HIIT change = 9.9 ± 3.5 %; p = 0.026). Moreover, there was a significant time × group interaction for maximum oxygen consumption (VO2max; CG change = -1.1 ± 1.0 mL/kg/min, HIIT change = 4.8 ± 0.9 mL/kg/min; p < 0.001)]. However, In patients with OSA, 12 weeks of HIIT decreases sleep apnea severity, improves sleep quality, and cardiorespiratory fitness. CLINICAL TRIAL REGISTRATION: (Registro Brasileiro de Ensaios Clínicos [ReBec]): # RBR-98jdt3.


[Characterization of hyper-responder patients to cardiac resynchronization therapy].
To compare clinical and echocardiographic characteristics of the hyper-responders to cardiac resynchronization therapy (CRT) with the rest of patients. We included 80 consecutive patients treated with CRT. The follow up was 19 (14) months. Patients were considered hyper-responder if they had an ejection fraction of left ventricle (LVEF) ≥ 50% after follow up. Twelve (15%) patients were considered hyper-responders. Their baseline clinical characteristics were similar to the rest except that there were fewer males in the group of hyper-responders. In these patients, basal left ventricle diastolic diameter was 64 (7) mm and the systolic was 55 (6) mm versus 75 (8) mm and 66 (9) mm respectively, p < 0.05. The basal area of mitral regurgitation in the hyper-responders was 3.1 (1.8) cm(2) versus 6.4 (5.5) cm(2), p < 0.05. Hyper-responder patients are often women with less dilated left ventricle and reduced severity of mitral regurgitation assessed by echocardiography.


Mapping the uroporphyrinogen decarboxylase, coproporphyrinogen oxidase and ferrochelatase loci in Bacillus subtilis.
Three genes hemE, hemF, hemG taking part in the porphyrin biosynthesis of Baccillus subtilis were mapped by two- and three-factor transduction crosses. The gene hemE determines uroporphyrinogen decarboxylase (EC 126.96.36.199) the gene hemF coproporphyrinogen oxidase (EC 184.108.40.206) and the gene hemG ferrochelatase (EC 18.104.22.168) enzymes. The loci hemE, hemF, hemG, are not linked to hemA locus and located near the argC and metD loci.


Assessment of cone beam CT registration for prostate radiation therapy: fiducial marker and soft tissue methods.
This investigation aimed to assess the consistency and accuracy of radiation therapists (RTs) performing cone beam computed tomography (CBCT) alignment to fiducial markers (FMs) (CBCTFM ) and the soft tissue prostate (CBCTST ). Six patients receiving prostate radiation therapy underwent daily CBCTs. Manual alignment of CBCTFM and CBCTST was performed by three RTs. Inter-observer agreement was assessed using a modified Bland-Altman analysis for each alignment method. Clinically acceptable 95% limits of agreement with the mean (LoAmean ) were defined as ±2.0 mm for CBCTFM and ±3.0 mm for CBCTST . Differences between CBCTST alignment and the observer-averaged CBCTFM (AvCBCTFM ) alignment were analysed. Clinically acceptable 95% LoA were defined as ±3.0 mm for the comparison of CBCTST and AvCBCTFM . CBCTFM and CBCTST alignments were performed for 185 images. The CBCTFM 95% LoAmean were within ±2.0 mm in all planes. CBCTST 95% LoAmean were within ±3.0 mm in all planes. Comparison of CBCTST with AvCBCTFM resulted in 95% LoA of -4.9 to 2.6, -1.6 to 2.5 and -4.7 to 1.9 mm in the superior-inferior, left-right and anterior-posterior planes, respectively. Significant differences were found between soft tissue alignment and the predicted FM position. FMs are useful in reducing inter-observer variability compared with soft tissue alignment. Consideration needs to be given to margin design when using soft tissue matching due to increased inter-observer variability. This study highlights some of the complexities of soft tissue guidance for prostate radiation therapy.


The discovery of potent, orally bioavailable pyrimidine-5-carbonitrile-6-alkyl CXCR2 receptor antagonists.
A hit-to-lead optimisation programme was carried out on the Novartis archive screening hit, pyrimidine 2-((2,6-dichlorobenzyl)thio)-5-isocyano-6-phenylpyrimidin-4-ol 4, resulting in the discovery of CXCR2 receptor antagonist 2-((2,3-difluorobenzyl)thio)-6-(2-(hydroxymethyl)cyclopropyl)-5-isocyanopyrimidin-4-ol 24. The SAR was investigated by systematic variation of the aromatic group at c-6, the linker between c-2 and the halogenated ring, and the c-5 nitrile moiety.


WALANT: Perceptions, approaches, and contraindications in a tertiary hand surgery unit.
Wide awake local anesthetic no tourniquet (WALANT) is gaining popularity amongst hand surgeons. Digital adrenaline use has been shown to be safe in multiple studies and the misconception forbidding it is receding. Phentolamine has been shown to safely reverse the effects of adrenaline should the feared complication of digital ischemia occur. A survey was circulated to 40 specialist practitioners who regularly perform hand procedures at a major tertiary plastic and hand surgery unit. Knowledge and understanding of WALANT, onset and duration of adrenaline effects and reversal was assessed. Whilst the majority of respondents (80%) recognized digital adrenaline use as safe, only 65% were aware of the delay until adrenaline takes full effect. Similarly, only 25% of respondents were aware of the duration of effect of adrenaline. Half of respondents were aware that phentolamine is the established reversal agent for adrenaline with only 20% knowing the correct dose. Given the lack of clinician knowledge surrounding adrenaline and its reversal, we feel that to safely undertake WALANT surgery at our Unit a WALANT protocol must be implemented. Drawing on the successes in the airline industry, a variety of safety frameworks have been established to deliver targeted education for prevention and eventual management of predictable risks. We plan to develop a checklist style protocol targeting the knowledge gaps raised in the survey. This will educate and equip all practitioners working with adrenaline with the knowledge to safely manage complications should they occur. LEVEL OF EVIDENCE: Level 5 (UK Oxford Centre for Evidence based Medicine (CEBM) Levels of Evidence).


Effectiveness of a psychological online training to promote physical activity among students: protocol of a randomized-controlled trial.
Many students in Germany do not meet recommended amounts of physical activity. In order to promote physical activity in students, web-based interventions are increasingly implemented. Yet, data on effectiveness of web-based interventions in university students is low. Our study aims at investigating a web-based intervention for students. The intervention is based on the Health Action Process Approach (HAPA), which discriminates between processes of intention formation (motivational processes) and processes of intention implementation (volitional processes). Primary outcome is change in physical activity; secondary outcomes are motivational and volitional variables as proposed by the HAPA as well as quality of life and depressive symptoms. A two-armed randomized controlled trial (RCT) of parallel design is conducted. Participants are recruited via the internet platform StudiCare ( www.studicare.com ). After the baseline assessment (t1), participants are randomized to either intervention group (immediate access to web-based intervention) or control group (access only after follow-up assessment). Four weeks later, post-assessment (t2) is performed in both groups followed by a follow-up assessment (t3) 3 months later. Assessments take place online. Main outcome analyses will follow an intention-to-treat principle by including all randomized participants into the analyses. Outcomes will be analysed using a linear mixed model, assuming data are missing at random. The mixed model will include group, time, and the interaction of group and time as fixed effects and participant and university as random effect. This study is a high-quality RCT with three assessment points and intention-to-treat analysis meeting the state-of-the-art of effectiveness studies. Recruitment covers almost 20 universities in three countries, leading to high external validity. The results of this study will be of great relevance for student health campaigns, as they reflect the effectiveness of self-help interventions for young adults with regard to behaviour change as well as motivational and volitional determinants. From a lifespan perspective, it is important to help students find their way into regular physical activity. The German clinical trials register (DRKS) DRKS00016889 . Registered on 28 February 2019.


PERSEIA: a biomedical wireless sensor network to support healthcare delivery for the elderly and chronically ill.
This paper presents a system based on ambient intelligence (AmI) to foster home care monitoring of senior citizens and chronically ill patients. The most important fact addressed in this research is the development of non intrusive and easy to use sensing devices. According to this, medical tests do not need user collaboration to perform them, neither powering on and off the sensor, starting the measure, configuring communications, etc.


Changes in macrophage and inflammatory cytokine expressions during fracture healing in an ovariectomized mice model.
Macrophages and inflammatory cytokines play important roles in bone fracture healing. However, the expression patterns of macrophages and inflammatory cytokines during fracture healing under the condition of postmenopausal osteoporosis have not been fully revealed. Tibia transverse fracture was established 12 weeks after ovariectomy or sham operation in 16-week old female mice. Tibias were harvested before fracture or 1, 3, 5, 7, 14, 21, 28 days after fracture for radiological and histological examinations. M1/M2 inflammatory macrophages, osteal macrophages and gene expressions of tumor necrosis factor-α, interleukin-6, interleukin-1β and macrophage conversion related molecules in the fracture haematoma or callus were also detected. The processes of fracture healing, especially the phases of endochondral ossification and callus remodeling, were delayed in ovariectomized mice. The expressions of tumor necrosis factor-α and interleukin-6, but not interleukin-1β, in the fracture haematoma or callus were disturbed. Expressions of tumor necrosis factor-α were decreased at 1, 14 and 21 days post-fracture (DPF), and were increased at 3, 5 and 7 DPF. Interleukin-6 expressions at 1, 3 and 21 DPF were significantly increased. We found the decreases in M1 and M2 macrophages at 1 DPF of the initial inflammatory stage. M2 macrophages at 14 DPF of the middle stage and osteal macrophages at 14, 21 and 28 DPF of the middle and late stages of fracture healing were also reduced in ovariectomized mice. The expressions of macrophages and inflammatory cytokines were impaired in ovariectomized mice, which might contribute partially to poor fracture healing.