Low temperature degradation of a Y-TZP dental ceramic.
Bars of Y-TZP ceramic for dental restorations were subjected to hydrothermal degradation via in vitro exposure to water steam at 140°C for 7 days. X-ray diffraction, atomic force microscopy and scanning electron microscopy techniques were applied to observe and quantify the tetragonal-monoclinic (t-m) phase transformation associated with the process. Nanoindentation was used to assess the ceramic's mechanical properties before and after hydrothermal degradation. Texture associated with martensitic t-m transformation was observed at the grain surface. The t-m transformation followed nucleation-and-growth kinetics, with predominance of the nucleation process. The transformation occurred within a layer of 6 μm below the surface. Mechanical properties deteriorated with hydrothermal degradation, resulting in a 30% reduction of Young's modulus and hardness. A strong correlation was found between the increasing monoclinic fraction and the decline in mechanical response. It was thus concluded that the emergence of the monoclinic phase and the associated microcracking were the most likely causes for the degradation of mechanical properties.


Comparison of In-Hospital Major Adverse Cardiovascular Events in Patients with Acute Myocardial Infarction Treated with Ticagrelor or Clopidogrel in the Emergency Department: A Propensity Score Matched Retrospective Cohort Study.
Dual antiplatelet therapy (DAPT) is a standard treatment option for acute myocardial infarction (AMI). The difference between the efficacy of ticagrelor and clopidogrel in the emergency department (ED) before percutaneous coronary intervention (PCI) remains unknown. The present study compared the in-hospital major adverse cardiovascular event (MACE) rates between patients with AMI treated with clopidogrel and those treated with ticagrelor in the ED before PCI. We retrospectively collected the data of patients diagnosed as having AMI in the ED. Patients were only included if they had successfully received complete DAPT with aspirin and ticagrelor/clopidogrel in the ED and had undergone PCI. The patients were divided into two groups according to their DAPT regimen. The primary outcome was the rate of in-hospital MACEs. The secondary outcomes included an unexpected return to the ED within 72 h, readmission within 14 d, and revascularization. A total of 1836 patients were enrolled. Patients in the ticagrelor group had a lower in-hospital MACE rate (3.01% versus 7.51%, p < 0.001) and in-hospital mortality rate (2.15% versus 5.70%, p < 0.001) than those in the clopidogrel group. Multivariate logistic regression analysis revealed ticagrelor was independently associated with a lower risk of in-hospital MACEs (odds ratio [OR]: 0.53, 95% CI: 0.32-0.88, p = 0.013). After propensity score matching, the risk of in-hospital MACEs remained significantly lower in the ticagrelor group (OR 0.42, 95% CI: 0.21-0.85, p = 0.016). DAPT with ticagrelor and aspirin in the ED before PCI is associated with a lower in-hospital MACE rate among patients with AMI.


Comparison of the lipid-lowering effect of clofibrate, and of clofibrate plus beta-pyridylcarbinol.
Forty-eight patients under 65 years were included in a double blind study comparing the lipid-lowering effect of clofibrate with that of beta-pyridylcarbinol combined with clofibrate. Over 4 months there was no significant difference in the lipid-lowering effect of either regime. A mean reduction of triglyceride of approximately 30% and of cholesterol of 18% was observed. Both drugs caused significantly greater reductions than placebo. No serious side-effects were noted.


The influence of antigen targeting to sub-cellular compartments on the anti-allergic potential of a DNA vaccine.
Gene vaccines offer attractive rationales for prophylactic as well as therapeutic treatments of type I allergies. DNA and mRNA vaccines have been shown to prevent from allergic sensitization and to counterbalance established allergic immune reactions. Recent advances in gene vaccine manipulation offer additional opportunities for modulation of T helper cell profiles by specific targeting of cellular compartments. DNA vaccines encoding the major birch pollen allergen Bet v 1.0101 were equipped with different leader sequences to shuttle the antigen to lysosomes (LIMP-II), to trigger cellular secretion (hTPA), or to induce proteasomal degradation via forced ubiquitination (ubi). Mice were pre-vaccinated with these constructs and the protective efficacy was tested by subcutaneous Th2-promoting challenges, followed by allergen inhalation. IgG antibody subclass distribution and allergen-specific IgE as well as cytokine profiles from re-stimulated splenocytes and from BALFs were assessed. The cellular composition of BALFs, and lung resistance and compliance were determined. Immunization with all targeting variants protected from allergic sensitization, i.e. IgE induction, airway hyperresponsiveness, lung inflammation, and systemic and local Th2 cytokine expression. Surprisingly, protection did not clearly correlate with the induction of a systemic Th1 cytokine profile, but rather with proliferating CD4+ CD25+ FoxP3+ T regulatory cells in splenocyte cultures. Targeting the allergen to proteasomal or lysosomal degradation severely down-regulated antibody induction after vaccination, while T cell responses remained unaffected. Although secretion of antigen promoted the highest numbers of Th1 cells, this vaccine type was the least efficient in suppressing the establishment of an allergic immune response. This comparative analysis highlights the modulatory effect of antigen targeting on the resulting immune response, with a special emphasis on prophylactic anti-allergy DNA vaccination. Targeting the antigen to proteasomal or lysosomal degradation reduces the availability of native allergen, thereby rendering the vaccine hypoallergenic without compromising efficacy, an important feature for a therapeutic setting.


Synthesis, characterization and biological studies of new antimony(III) halide complexes with ω-thiocaprolactam.
Three new antimony(III) halide complexes (SbX(3), X=Cl, Br and I) with the heterocyclic thione ω-thiocaprolactam (1-azacycloheptane-2-thione, (Hthcl)) of formulae {[SbCl(2)(μ(2)-Cl)(Hthcl)(2)](n)} (1), {[(SbBr(2)(μ(2)-Br)(Hthcl)(2))(2)]} (2) and {[(SbI(2)(μ(2)-I)(Hthcl)(2))(2)]} (3) were synthesized from the reaction of antimony(III) halides with ω-thiocaprolactam in 1:2 stoichiometry. The complexes were characterized by elemental analysis, FT-IR spectroscopy, (1)H, (13)C NMR spectroscopy and Thermal Gravimetry-Differential Thermal Analysis (TG-DTA). Crystal structures of the ligand ω-thiocaprolactam and its complexes 1-3 were determined with single crystal X-ray diffraction analysis. Complexes 1-3 and ω-thiocaprolactam were evaluated for their in vitro cytotoxic activity against leiomyosarcoma (LMS) and human breast adenocarcinoma (MCF-7) tumor cell lines. Antimony complexes 1-3 exhibit strong antiproliferative activity against both cell lines tested. The higher such activity was found for 3 with IC(50) values of 0.12±0.04 μM (LMS) and 0.76±0.16 μM (MCF-7) which are 60 and 10 times respectively, stronger than that of cisplatin. The influence of these complexes 1-3 and ω-thiocaprolactam upon the catalytic peroxidation of linoleic acid to hyperoxolinoleic acid by the enzyme lipoxygenase (LOX) was kinetically and theoretically studied. The results were shown negligible inhibitory activity of 1-3 against LOX.


[Comparative study on clinical efficacy of using methotrexate singly or combined with total glucosides of Paeony in treating rheumatoid arthritis].
To observe the clinical efficacy of methotrexate (MTX) combined with total glucosides of Peony (TGP) on rheumatoid arthritis (RA). Sixty-one RA patients were divided into 2 groups, 30 patients in the MTX group were only administered orally with MTX, while 31 patients in the combined treated group were treated with MTX plus TGP, the therapeutic course for both groups was 3 months. The total effective rate was 90%, 94%, 100% in the MTX plus TGP group, and 87%, 90%, 94% in the MTX group at 4, 8 and 12 weeks after treatment respectively, comparison of the therapeutic effect between the two groups showed insignificant difference (P > 0.05). The erythrocyte sedimentation rate (ESR) and the level of C-reactive protein were significantly decreased in both groups, but the decrement in the MTX plus TGP group was more than those in the MTX group. MTX plus TGP treatment is characterized by quick initiating, with stable clinical efficacy, few side effects and high compliance, it is more suitable for aged RA patients.


Organoids as a tool in drug discovery and patient-specific therapy for head and neck cancer.
Organoids more accurately reflect tumor microenvironment than traditional models. Millen et al. demonstrated organoids replicated from patient tissues may predict patient-specific response to radiation therapy and have potential to be utilized for validation of biomarkers in drug discovery and treatment planning.


A missense mutation of STERILE APETALA leads to female sterility in Chinese cabbage (Brassica campestris ssp. pekinensis).
Flower development is essential for the sexual reproduction and crop yield of plants. Thus, a better understanding of plant sterility from the perspective of morphological and molecular genetics is imperative. In our previous study, a recessive female-sterile Chinese cabbage mutant fsm was obtained from a doubled haploid line 'FT' via an isolated microspore culture combined with EMS mutagenesis. Pistil aniline blue staining and stigma scanning observation showed that the growth of the stigma papillar cells and pollen tubes of the mutant fsm were normal. Therefore, the female sterility was due to abnormal development of the ovules. To map the mutant fsm, 3108 F2 individuals were selected for linkage analysis. Two closely linked markers, Indel-I2 and Indel-I7, were localized on the flanking region of fsm at distances of 0.05 cM and 0.06 cM, respectively. The physical distance between Indel-I2 and Indel-I7 was ~ 1376 kb, with 107 genes remaining in the target region. This region was located on the chromosome A04 centromere, on which low recombination rates and a high frequency of repetitive sequences were present. Whole-genome re-sequencing detected a single-nucleotide (C-to-A) transition (TCG/TAG) on the exon of BraA04001030, resulting in a premature stop codon. Genotyping revealed that the female-sterile phenotype was fully cosegregated with this SNP. BraA04001030 encodes a homologue of STERILE APETALA (SAP) transcriptional regulator, which plays vital roles in floral development. The results of the present study suggest that BraA04001030 is a strong candidate gene for fsm and provide the basis for exploring the molecular mechanism underlying female sterility in Chinese cabbage.


Data, and sample sources thereof, on water quality life cycle impact assessments pertaining to catchment scale acidification and eutrophication potentials and the benefits of on-farm mitigation strategies.
Based on recent spatially aggregated June Agriculture Survey data and site-specific environmental data, information from common farm types in the East of England was sourced and collated. These data were subsequently used as key inputs to a mechanistic environmental modelling tool, the Catchment Systems Model, which predicts environmental damage arising from various farm types and their management strategies. The Catchment Systems Model, which utilises real-world agricultural productivity data (samples and appropriate consent provided within the Mendeley Data repository) is designed to assess not only losses to nature such as nitrate, phosphate, sediment and ammonia, but also to predict how on-farm intervention strategies may affect environmental performance. The data reported within this article provides readers with a detailed inventory of inputs such as fertiliser, outputs including nutrient losses, and impacts to nature for 1782 different scenarios which cover both arable and livestock farming systems. These 1782 scenarios include baseline (i.e., no interventions), business-as-usual (i.e., interventions already implemented in the study area) and optimised (i.e., best-case scenarios) data. Further, using the life cycle assessment (LCA) methodology, the dataset reports acidification and eutrophication potentials for each scenario under two (eutrophication) and three (acidification) impact assessments to offer an insight into the importance of impact assessment choice. Finally, the dataset also provides its readers with percentage changes from baseline to best-case scenario for each farm type.


A computational modeling and analysis in cell biological dynamics using electric cell-substrate impedance sensing (ECIS).
In this paper, a study of computational modeling and multi-scale analysis in cell dynamics is presented. Our study aims at: (1) deriving and validating a mathematical model for cell growth, and (2) quantitatively detecting and analyzing the biological interdependencies across multiple observational scales with a variety of time and frequency resolutions. This research was conducted using the time series data practically measured from a novel on-line cell monitoring technique, referred to as electric cell-substrate impedance sensing (ECIS), which allows continuously tracking the cellular behavior such as adhesion, proliferation, spreading and micromotion. First, comparing our ECIS-based cellular growth modeling analysis results with those determined by hematocytometer measurement using different time intervals, we found that the results obtained from both experimental methods consistently agreed. However, our study demonstrated that it is much easier and more convenient to operate with the ECIS system for on-line cellular growth monitoring. Secondly, for multi-scale analysis our results showed that the proposed wavelet-based methodology can effectively quantify the fluctuations associated with cell micromotions and quantitatively capture the biological interdependencies across multiple observational scales. Note that although the wavelet method is well known, its application into the ECIS time series analysis is novel and unprecedented in computational cell biology. Our analyses indicated that the proposed study on ECIS time series could provide a hopeful start and great potentials in both modeling and elucidating the complex mechanisms of cell biological systems.


Low-level illegitimate transcription of genes may be to silence the genes.
In yeast and plants, low level transcription of a gene is recently revealed to be required to repress the gene. It may account for the widely low level illegitimate transcriptions of tissue-specific genes reported in mammalian cells. This hypothetical link gives insight into both analysis of transcription-associated evolutionary events and further interpretation of the mechanism of small RNA-mediated transcriptional repression.


Determination of amyloid beta protein precursors harboring active form of proteinase inhibitor domains in cerebrospinal fluid of Alzheimer's disease patients by trypsin-antibody sandwich ELISA.
beta-Amyloid protein precursors (APP) having proteinase inhibitor domains (APPI) were quantified by a new sandwich enzyme linked immunosorbent assay for detection of active (free) form of proteinase inhibitors by using trypsin in place of the first antibody and by denaturation of APPI-trypsin complex in the microtiterplate. The concentration of APPs having APPI in cerebrospinal fluid of Alzheimer's disease patients was found, by this method, to be significantly elevated compared with those of multi-infarct dementia.


Bridging the gap: Hospital to workplace.
Work-oriented neurorehabilitation to return to competitive employment after a serious neurologic illness or injury is an interdisciplinary process that begins as soon as pathology has stabilized. This bimonthly column provides narratives of anonymized clients in situations that challenge their return-to-work. Each case study is designed for postgraduate education about tools and methods that are appropriate to consider in similar situations. Through case studies of adults attempting to return to safe and dependable competitive employment, real-world issues are explored that occur at the interface between the client and their employer. The current case describes Structured Task Self Appraisal (STSA), a forensic rehabilitation method to collect self-report baseline information concerning the client's job-relevant functional limitations. STSA guides return-to-work rehabilitation services. Information concerning the core tasks and important abilities of the client's target occupation that are immediately available in O*NET can be analyzed in a structured manner to provide the workplace context for rehabilitation.


Stress-induced immunosuppression increases levels of certain circulating miRNAs and affects the immune response to an infectious bursal disease virus vaccine in chickens.
Stress-induced immunosuppression can affect the immune effect of vaccine. However, the mechanism of stress-induced immunosuppression affecting immune response to infectious bursal disease virus (IBDV) vaccine in chicken is still unclear. In this study, thirteen IBDV related circulating miRNAs were selected to study their expressions, possible functions and mechanisms in dexamethasone (Dex)-induced immunosuppressed chicken vaccinated with IBDV attenuated vaccine. The experiment aimed to explore the relationship between the expressions of IBDV related circulating miRNAs and stress-induced immunosuppression. The quantitative real-time PCR (qRT-PCR) results showed that Dex-induced immunosuppression could induce the differential expressions of the candidate serum circulating miRNAs, especially on the 2nd, 5th, 7th and 28th day after dexamethasone treatment. Dex-induced immunosuppression could affect the immune response to the IBDV vaccine, which was possibly achieved by partially regulating the differential expressions of the IBDV related circulating miRNAs. Bioinformatics analysis showed that the candidate miRNAs could regulate the immune function mainly through targeting genes (such as CREB1 and MAPK1) in TGF-β and MAPK signaling pathways. This study can provide a preliminary reference for further studying the function and mechanism of circulating miRNAs in immune regulation.


Observation of topological structures in photonic quantum walks.
Phases of matter with nontrivial topological order are predicted to exhibit a variety of exotic phenomena, such as robust localized bound states in 1D systems, and edge states in 2D systems, which are expected to display spin helicity, immunity to backscattering, and weak antilocalization. In this Letter, we present an experimental observation of topological structures generated via the controlled implementation of two consecutive noncommuting rotations in photonic discrete-time quantum walks. The second rotation introduces valleylike Dirac points in the system, allowing us to create the nontrivial topological pattern. By choosing specific values for the rotations, it is possible to coherently drive the system between topological sectors characterized by different topological invariants. We probe the full topological landscape, demonstrating the emergence of localized bound states hosted at the topological boundaries, and the existence of extremely localized or delocalized non-Gaussian quantum states. Our results pave the way for the study of valley polarization and applications of topological mechanisms in robust optical-device engineering.


Total joint arthroplasty in patients with chronic infectious liver disease.
The opportunity for total joint arthroplasty (TJA) in patients with chronic infectious liver disease is rapidly expanding. This is the product of both superior survival of chronic hepatitis patients, evolving implant technologies, and improvement of techniques in TJA. Unfortunately, treating this group of patients is not without significant challenges that can stem from both intrahepatic and extrahepatic clinical manifestations. Moreover, many subclinical changes occur in this cohort that can alter hemostasis, wound healing, and infection risk even in the asymptomatic patient. In this review, we discuss the various clinical presentations of chronic infectious liver disease and summarize the relevant literature involving total joint arthroplasty for this population. Hopefully, through appropriate patient selection and perioperative optimization, treating surgeons should see continued improvement in outcomes for patients with chronic infectious liver disease.


Identification of members of Mycobacterium avium species by Accu-Probes, serotyping, and single IS900, IS901, IS1245 and IS901-flanking region PCR with internal standards.
From Mycobacterium avium species Mycobacterium avium subsp. paratuberculosis (n=961), Mycobacterium a. avium (n=677), Mycobacterium a. silvaticum (n=5), and Mycobacterium a. hominissuis (n=1566) were examined, and from Mycobacterium tuberculosis complex M. tuberculosis (n=2), Mycobacterium bovis (n=13), M. bovis BCG (n=4), and Mycobacterium caprae (n=10) were examined. From other mycobacterial species Mycobacterium intracellulare (n=60) and atypical mycobacteria (n=256) including Mycobacterium fortuitum, Mycobacterium chelonae, Mycobacterium scrofulaceum, Mycobacterium gastri and other species of conditionally pathogenic mycobacteria were analysed. The internal standard molecules corresponding to insertion sequences IS900, IS901, IS1245, and flanking region (FR300) of IS901 were produced by PCR of alfalfa genome segment and inserted into plasmid vector. The resulting recombinant plasmid molecules were used as internal standards in coamplification with a total of 4729 mycobacterial collection strains and field isolates between 1996 and 2003. The size differences between amplicons obtained from IS900 (258 bp), IS901 (1108 bp), IS1245 (427 bp), and FR300 (300 bp) and from corresponding internal standard molecules ISIS900 (591 bp), ISIS901 (1 336 bp), ISIS1245 (583 bp), and IS901 flanking region of 300 bp ISFR300 (488 bp), respectively, allowed easy discrimination. The internal amplicons were visible by naked aye on agarose gel when 10(1), 10(3), 10(2), and 10(2) molecules for ISIS900, ISIS901, ISIS1245, and ISFR300 were used in the PCR, respectively, when no bacterial DNA was added to the reaction. The system was tested to define the amount of internal standards that could be used in the PCR without affecting the amplification of the specific segment. Non-specific amplifications were observed in M. fortuitum with IS1245 PCR and mixed infections with M. a. avium and M. a. hominissuis from pigs and cattle were found. PCR results of typing were compared with serotyping and Accu-Probes analyses in selected field isolates.


Prenatal diagnosis and planned peri-partum care as a strategy to improve pre-operative status in neonates with critical CHDs in low-resource settings: a prospective study.
Prenatal diagnosis and planned peri-partum care is an unexplored concept for care of neonates with critical CHDs in low-middle-income countries. To report the impact of prenatal diagnosis on pre-operative status in neonates with critical CHD. Prospective observational study (January 2017-June 2018) in tertiary paediatric cardiac facility in Kerala, India. Neonates (<28 days) with critical CHDs needing cardiac interventions were included. Pre-term infants (<35 weeks) and those without intention to treat were excluded. Patients were grouped into those with prenatal diagnosis and diagnosis after birth. Main outcome measure was pre-operative clinical status. Total 119 neonates included; 39 (32.8%) had prenatal diagnosis. Eighty infants (67%) underwent surgery while 32 (27%) needed catheter-based interventions. Pre-operative status was significantly better in prenatal group; California modification of transport risk index of physiological stability (Ca-TRIPS) score: median 6 (0-42) versus 8 (0-64); p < 0.001; pre-operative assessment of cardiac and haemodynamic status (PRACHS) score: median 1 (0-4) versus 3 (0-10), p < 0.001. Age at cardiac procedure was earlier in prenatal group (median 5 (1-26) versus 7 (1-43) days; p = 0.02). Mortality occurred in 12 patients (10%), with 3 post-operative deaths (2.5%). Pre-operative mortality was higher in postnatal group (10% versus 2.6%; p = 0.2) of which seven (6%) died due to suboptimal pre-operative status precluding surgery. Prenatal diagnosis and planned peri-partum care had a significant impact on the pre-operative status in neonates with critical CHD in a low-resource setting.


Surface composition of myrmecophilic plants: cuticular wax and glandular trichomes on leaves of Macaranga tanarius.
Primary plant surfaces, covered with cuticles consisting of cutin and waxes, are important substrates for interaction with insects. The composition of leaf surfaces of the myrmecophilic plant Macaranga tanarius was studied. The prenylated flavanone nymphaeol-C was identified in surface extracts and was localized exclusively in glandular trichomes on the abaxial leaf side. The epidermal pavement cells surrounding these trichomes were covered with a smooth film of epicuticular wax from which few small wax crystals protruded. The epicuticular wax amounted to approximately 8 microg cm(-2), corresponding to 85% of the wax load on the adaxial as well as the abaxial leaf sides. The epicuticular wax mixtures from both leaf surfaces contained more than 70% primary alcohols, 14% fatty acids, 2% aldehydes, and traces of alkyl acetates, with chain lengths ranging from C(20) to C(38). In contrast, the intracuticular wax layer was largely dominated by triterpenoid alcohols alpha-amyrin, beta-amyrin, and lupeol. Consequently, these characteristic compounds are not available for direct contact with insects on the plant surface.


Use of a reverse micelle system for study of oligomeric structure of NAD+-reducing hydrogenase from Ralstonia eutropha H16.
Inclusion of an oligomeric enzyme, NAD+-dependent hydrogenase from the hydrogen-oxidizing bacterium Ralstonia eutropha, into a system of reverse micelles of different sizes resulted in its dissociation into catalytically active heterodimers and subunits, which were characterized in reactions with various substrates. It was found that: 1) the native tetrameric form of this enzyme catalyzes all types of studied reactions; 2) hydrogenase dimer, HoxHY, is a minimal structural unit catalyzing hydrogenase reaction with an artificial electron donor, reduced methyl viologen; 3) all structural fragments containing FMN and NAD+/NADH-binding sites exhibit catalytic activity in diaphorase reactions with one- and two-electron acceptors; 4) small subunits, HoxY and HoxU also exhibit activity in diaphorase reactions with artificial acceptors. These results can be considered as indirect evidence that the second FMN molecule may be associated with one of the small subunits (HoxY or HoxU) of the hydrogenase from R. eutropha.


Radicals in stereoselective synthesis and electron transfer reactions.
This short historical review describes the work of the Giese group on radicals and radical ions that has led to the award of the Paracelsus prize in 2012.


Electrode Array Type and Its Impact on Impedance Fluctuations and Loss of Residual Hearing in Cochlear Implantation.
Determine variables associated with electrode impedance fluctuations and loss of residual hearing in cochlear implant (CI) recipients. CI recipients with postoperative hearing preservation demonstrate superior speech perception with an electric-acoustic stimulation (EAS) device as compared with a CI-alone device. Maintaining superior speech perception over time relies on long-term hearing preservation; therefore, understanding variables that may contribute to loss of residual hearing is needed. Recent reports suggest a relationship between changes in electrode impedance and loss of residual hearing. The variables influencing this relationship have yet to be determined. Review of pediatric and adult CI cases from 2013 to 2016 who presented with preoperative residual hearing. Regression analysis was performed to evaluate effects of array type (lateral wall vs. perimodiolar), manufacturer, age at implantation, and preoperative hearing on impedance. The correlation between peak impedance change and change in low-frequency hearing was determined. One hundred forty-six CI recipients presented with preoperative residual hearing. A multivariate regression analysis demonstrated a statistically significant association between preoperative hearing thresholds (p = 0.017), device manufacturer (p = 0.011), and array type (p = 0.038) on postoperative impedance changes. Hearing preservation rates and change in impedance differed by electrode array type. The association between peak impedance changes and loss of residual hearing differed between manufacturers (R = 0.208, p = 0.029 vs. R = 0.016, p = 0.609). Impedance fluctuation appears to be a marker for loss of residual hearing for specific electrode array types and manufacturers. Specific arrays may affect the cochlear microenvironment differently, with different effects on postoperative hearing preservation.


Effect of 'activity monitor-based' counseling on physical activity and health-related outcomes in patients with chronic diseases: A systematic review and meta-analysis.
This review evaluated the effects of activity monitor-based counseling on physical activity (PA) and generic and disease-specific health-related outcomes in adults with diabetes mellitus type II (DMII), chronic obstructive pulmonary disease (COPD), or chronic heart failure (CHF). Four electronic databases were searched for randomized controlled trials using activity monitor-based counseling versus control intervention or usual care in adults with DMII, COPD, or CHF. Pooled effect sizes were calculated using a random effects model. Twenty-four articles were included: 21 DMII studies and 3 COPD studies. No CHF studies were identified. Pooled analysis showed that activity monitor-based counseling resulted in a significantly greater improvement in PA compared to control intervention or usual care in DMII. Furthermore, these interventions had a beneficial effect on hemoglobin A1c (HbA1c), systolic blood pressure, and body mass index (BMI) (P < 0.05), whereas no differences were found on diastolic blood pressure, and health-related quality of life. Meta-analysis of COPD studies was not possible due to lack of available data. Activity monitor-based counseling had a beneficial effect on PA, HbA1c, systolic blood pressure, and BMI in patients with DMII. Data in patients with COPD and CHF are limited or non-existing, respectively.


The effect of anti-human leukocyte antigen, anti-major histocompatibility complex class 1 chain-related antigen a, and anti-glutathione transferase-T1 antibodies on the long-term survival of renal allograft.
One of the most important mechanisms of allograft rejection is the production of donor-specific antibodies (DSA). Anti-major histocompatibility complex class-I chain-related antigen A (MICA) and anti-glutathione S transferase-T1 (GSTT1) antibodies cause graft dysfunction and reduce graft survival. The aim of this study was to examine the effects of anti-human leukocyte antigen class I-II, anti-MICA, and anti-GSTT1 antibodies in development of antibody-mediated rejection. Among the 32 renal transplant patients included in this study 65% experienced antibody-mediated rejection (AMR; chronic active AMR [CAMR], n = 17; acute AMR [AAMR], n = 4) and 35%, ACR. The anti-HLA class I-II and anti-MICA antibodies were determined by using LUMINEX, anti-GSTT1 antibodies by enzyme-linked immunosorbent assay. GSTT1 genotyping of patients and donors was performed by polymerase chain reaction. Antibody was detected in 19 of 21 patients undergoing antibody-mediated rejection (90%). We detected anti-GSTT1 in 4, anti-MICA in 8, anti-HLA class I in 5, and anti-HLA class II in 9 patients with CAMR (P = .007). If the patients were divided into 2 groups according to being C4d(+) and C4d(-) both anti-HLA class I and class II antibodies were found significantly more frequently among the C4d(+) group (P = .019, P = .024). No difference was determined between AMR and ACR groups in terms of anti-GSTT1 and anti-MICA antibodies. In this study, we observed the role of anti-HLA class II antibodies in the development of CAMR and in long-term allograft survival. It is observed that anti-MICA and anti-GSTT1 antibodies showed no effect on rejection mechanisms.


Does a novel teaching approach work? A Students' perspective.
There is always a call for educational reform and further research to improve educational programs. The continuous development of new educational approaches is a work in progress. Educational strategies like team-based learning, flipped classroom, and lottery-based token economy, were used to develop a novel teaching approach. This study had two major goals. The first goal was to introduce a novel teaching approach in professional healthcare academies. The second goal was to get an in-depth understanding, from the students' perspective, about the benefits and limitations of this new teaching approach. The study was conducted using a qualitative, phenomenological research design. Third and fourth-year nursing students completed reflective journals to describe their personal experience with the new teaching approach at the end of the semester. The students' responses were analyzed and coded using Kember's four-category coding schema for reflective writing, to extract themes using thematic analysis. Seventy-five students completed and returned their reflective journals. The analysis showed various challenges and facilitators/benefits of the students' experiences. The themes that emerged from the analysis were: lack of exposure vs. a sense of achievement; lack of teamwork skills vs. role fulfillment; working with new people vs. conflict resolution; variation vs. collaboration/creativity; time management vs. constructive competition; wasting resources vs. flexibility, and proactivity/active engagement. These themes summarized why the new teaching approach worked and what barriers students faced with the new assembly. Results from the current study demonstrated the great potential of the new teaching approach. Recommendations for future research were also discussed.


miR-205 regulation of ICT1 has an oncogenic potential via promoting the migration and invasion of gastric cancer cells.
Immature colon carcinoma transcript-1 (ICT1) is a newly identified oncogene, which regulates mobility, apoptosis, cell cycle progression and proliferation of cancer cells. Nevertheless, the role of ICT1 and its clinical significance in gastric cancer (GC) is largely uncovered. Here, we found that ICT1 displayed higher expression in GC tissues compared to corresponding tumor-adjacent tissues. Further investigation confirmed ICT1 overexpression in GC cell lines. Clinical data disclosed that high ICT1 expression correlated with distant metastasis and advanced tumor-node-metastasis (TNM) stage. The Cancer Genome Atlas (TCGA) data further demonstrated that GC tissues with metastasis showed a significant higher level of ICT1 compared to those without metastasis. Furthermore, ICT1 overexpression notably predicted poor prognosis of GC patients. Functionally, we demonstrated that ICT1 knockdown suppressed invasion and migration of MGC-803 and BGC-823 cells in vitro. ICT1 overexpression promoted the mobility of SGC-7901 cells. Mechanistically, microRNA-205 (miR-205) was recognized as a direct down-regulator and inversely modulated ICT1 abundance in GC cells. miR-205 expression was down-regulated and negatively associated with ICT1 level in GC tissues. Underexpression of miR-205 indicated an obvious shorter survival of GC patients. miR-205 overexpression inhibited migration and invasion of MGC-803 cells, while these inhibitory effects were reversed by ICT1 restoration. Taken together, we have the earliest evidence that miR-205 regulation of ICT1 functions as an oncogene and prognostic biomarker in GC.


Pneumococcal vaccine.
Pneumococcal infections are common and serious infections, and their control is an important public health priority. A multivalent pneumococcal vaccine was introduced several years ago, but there is still controversy about its effectiveness in United States populations. One randomized controlled study in high-risk veterans did not demonstrate efficacy. The study has been criticized because the case definitions used for pneumococcal infection had uncertain specificity. Two large case control studies done in Pennsylvania and Connecticut hospitals have compared vaccination rates in patients with pneumococcal bacteremia with controls matched for disease severity and age. Bacteremic immunosuppressed patients who were unlikely to have responded to pneumococcal vaccine were excluded. These studies showed vaccine efficacy rates in the 60% to 70% range as did a prospective randomized controlled French trial that used episodes of pneumonia as an end point. Pneumococcal vaccine is effective when given to patients likely to respond immunologically and who are at increased risk from pneumococcal infection.


New iridal-type triterpenoid analogues with 6/5/6-fused carbon skeleton from the rhizomes of Belamcanda chinensis.
Five new iridal-type triterpenoid derivatives with 6/5/6 tricyclic ring skeleton (1-5) were obtained from the rhizomes of Belamcanda chinensis. Their structures were determined on the basis of detailed spectroscopic data and ECD calculation. Compounds 1-5 possessed the same 6/5/6-fused carbon skeleton as Belamchinenin A, which further enriched this kind of iridals. In vitro bioassay, compounds 2 and 3 exhibited 51.95 and 54.52% inhibitory activities, respectively, against Fe2+/cysteine-induced liver microsomal lipid peroxidation at a concentration of 10 μM. A putative biogenetic pathway for compounds 1-5 was proposed.


Biological processes in seagrass beds of coastal lagoons to maintain estuary-dependent marine fisheries.
Following the planned FAO Ecosystem Restoration Programme for estuarine habitats to support estuarine fisheries and early life stages of estuary-dependent marine fish, direct relationships of total seagrass and eelgrass Zostera m. capricorni areas and biomass with fish harvest were derived for a range of slightly to highly urbanized coastal lagoons that are expected to support the larvae and juveniles of estuary-dependent marine fisheries. Fish harvest and seagrass area and biomass in the lagoons increased with moderate catchment total suspended sediment and total phosphorus loads due to lagoon flushing rates directing excess silt and nutrients out to sea via the lagoon entrances. Well managed, sewered catchment management works are shown that could assist estuary managers maintain seagrass for estuarine and offshore estuary-dependent fisheries by maintenance of seagrass and fishery ecological processes. Further research is suggested to investigate estuary-dependent post-juveniles leaving estuaries and lagoons migrating to nearshore, offshore and shelf marine fisheries.


Insulin resistance and body fat distribution in South Asian men compared to Caucasian men.
South Asians are susceptible to insulin resistance even without obesity. We examined the characteristics of body fat content, distribution and function in South Asian men and their relationships to insulin resistance compared to Caucasians. Twenty-nine South Asian and 18 Caucasian non-diabetic men (age 27+/-3 and 27+/-3 years, respectively) underwent euglycemic-hyperinsulinemic clamp for insulin sensitivity, underwater weighing for total body fat, MRI of entire abdomen for intraperitoneal (IP) and subcutaneous abdominal (SA) fat and biopsy of SA fat for adipocyte size. Compared to Caucasians, in spite of similar BMI, South Asians had higher total body fat (22+/-6 and 15+/-4% of body weight; p-value<0.0001), higher SA fat (3.5+/-1.9 and 2.2+/-1.3 kg, respectively; p-value = 0.004), but no differences in IP fat (1.0+/-0.5 and 1.0+/-0.7 kg, respectively; p-value = 0.4). SA adipocyte cell size was significantly higher in South Asians (3491+/-1393 and 1648+/-864 microm2; p-value = 0.0001) and was inversely correlated with both glucose disposal rate (r-value = -0.57; p-value = 0.0008) and plasma adiponectin concentrations (r-value = -0.71; p-value<0.0001). Adipocyte size differences persisted even when SA was matched between South Asians and Caucasians. Insulin resistance in young South Asian men can be observed even without increase in IP fat mass and is related to large SA adipocytes size. Hence ethnic excess in insulin resistance in South Asians appears to be related more to excess truncal fat and dysfunctional adipose tissue than to excess visceral fat.


Approaches to Analysis in Model-based Cognitive Neuroscience.
Our understanding of cognition has been advanced by two traditionally nonoverlapping and non-interacting groups. Mathematical psychologists rely on behavioral data to evaluate formal models of cognition, whereas cognitive neuroscientists rely on statistical models to understand patterns of neural activity, often without any attempt to make a connection to the mechanism supporting the computation. Both approaches suffer from critical limitations as a direct result of their focus on data at one level of analysis (cf. Marr, 1982), and these limitations have inspired researchers to attempt to combine both neural and behavioral measures in a cross-level integrative fashion. The importance of solving this problem has spawned several entirely new theoretical and statistical frameworks developed by both mathematical psychologists and cognitive neuroscientists. However, with each new approach comes a particular set of limitations and benefits. In this article, we survey and characterize several approaches for linking brain and behavioral data. We organize these approaches on the basis of particular cognitive modeling goals: (1) using the neural data to constrain a behavioral model, (2) using the behavioral model to predict neural data, and (3) fitting both neural and behavioral data simultaneously. Within each goal, we highlight a few particularly successful approaches for accomplishing that goal, and discuss some applications. Finally, we provide a conceptual guide to choosing among various analytic approaches in performing model-based cognitive neuroscience.


Ultrarapid-Acting Microneedles for Immediate Delivery of Biotherapeutics.
Subcutaneous (SC) injection is a common administration route for rapid and efficient delivery of biotherapeutics. However, syringe-based injections usually require professional assistance and are associated with pain and potential risks of infections, thus leading to undesired patient compliance and poor life quality. Herein, this work presents an ultrarapid-acting microneedle (URA-MN) patch for immediate transdermal delivery of therapeutics in a minimally invasive manner. Effervescent agents are incorporated into the tip of URA-MN for rapid generation of CO2 bubbles upon insertion into the skin, immediately powering the biotherapeutics release within a few minutes. The release kinetics of diverse agents including liraglutide (LRT), insulin, and heparin from the URA-MN patches are evaluated in three different mouse models, and the rapid release of biotherapeutics and potent therapeutic effects are achieved with only 5 min administration. Noteworthily, attributed to the short application duration and negligible residuals of MN matrix remaining in the skin, the URA-MN patch shows desirable biocompatibility after six-week administration.


Ester percentages of plant sterols and cholesterol in chylomicrons and VLDL of humans with low and high sterol absorption.
Ester percentages of cholesterol and non-cholesterol sterols were measured in chylomicrons and very low density lipoproteins (VLDL) in 15 subjects. Our hypothesis was that in humans, in contrast to animal experiments, plant sterols in chylomicrons are esterified similarly to cholesterol. In fact, the mean ester percentage of chylomicron sitosterol (approximately 40%), but not of campesterol ( approximately 51%), was lower than that of cholesterol (approximately 54%) in the whole study population. In high cholesterol absorbers (high serum total campesterol, > or = 2.8 mmol/mol of cholesterol), the ester percentages of sitosterol and other non-cholesterol sterols were similar to that of cholesterol in chylomicrons, and the percentages tended to be higher than those in low absorbers. In contrast to chylomicrons, the ester percentages of sterols in VLDL tended to be lower in the high than low absorbers. In conclusion, percentages of plant sterol esters are not consistently lower than those of cholesterol in chylomicrons.


Multiplexing DNA methylation markers to detect circulating cell-free DNA derived from human pancreatic β cells.
It has been proposed that unmethylated insulin promoter fragments in plasma derive exclusively from β cells, reflect their recent demise, and can be used to assess β cell damage in type 1 diabetes. Herein we describe an ultrasensitive assay for detection of a β cell-specific DNA methylation signature, by simultaneous assessment of 6 DNA methylation markers, that identifies β cell DNA in mixtures containing as little as 0.03% β cell DNA (less than 1 β cell genome equivalent). Based on this assay, plasma from nondiabetic individuals (N = 218, aged 4-78 years) contained on average only 1 β cell genome equivalent/mL. As expected, cell-free DNA (cfDNA) from β cells was significantly elevated in islet transplant recipients shortly after transplantation. We also detected β cell cfDNA in a patient with KATP congenital hyperinsulinism, in which substantial β cell turnover is thought to occur. Strikingly, in contrast to previous reports, we observed no elevation of β cell-derived cfDNA in autoantibody-positive subjects at risk for type 1 diabetes (N = 32), individuals with recent-onset type 1 diabetes (<4 months, N = 92), or those with long-standing disease (>4 months, N = 38). We discuss the utility of sensitive β cell cfDNA analysis and potential explanations for the lack of a β cell cfDNA signal in type 1 diabetes.


Effectiveness of participatory women's groups scaled up by the public health system to improve birth outcomes in Jharkhand, eastern India: a pragmatic cluster non-randomised controlled trial.
The WHO recommends community mobilisation with women's groups practising participatory learning and action (PLA) to improve neonatal survival in high-mortality settings. This intervention has not been evaluated at scale with government frontline workers. We did a pragmatic cluster non-randomised controlled trial of women's groups practising PLA scaled up by government front-line workers in Jharkhand, eastern India. Groups prioritised maternal and newborn health problems, identified strategies to address them, implemented the strategies and evaluated progress. Intervention coverage and quality were tracked state-wide. Births and deaths to women of reproductive age were monitored in six of Jharkhand's 24 districts: three purposively allocated to an early intervention start (2017) and three to a delayed start (2019). We monitored vital events prospectively in 100 purposively selected units of 10 000 population each, during baseline (1 March 2017-31 August 2017) and evaluation periods (1 September 2017-31 August 2019). The primary outcome was neonatal mortality. We identified 51 949 deliveries and conducted interviews for 48 589 (93.5%). At baseline, neonatal mortality rates (NMR) were 36.9 per 1000 livebirths in the early arm and 39.2 in the delayed arm. Over 24 months of intervention, the NMR was 29.1 in the early arm and 39.2 in the delayed arm, corresponding to a 24% reduction in neonatal mortality (adjusted OR (AOR) 0.76, 95% CI 0.59 to 0.98), including 26% among the most deprived (AOR 0.74, 95% CI 0.57 to 0.95). Twenty of Jharkhand's 24 districts achieved adequate meeting coverage and quality. In these 20 districts, the intervention saved an estimated 11 803 newborn lives (min: 1026-max: 20 527) over 42 months, and cost 41 international dollars per life year saved. Participatory women's groups scaled up by the Indian public health system reduced neonatal mortality equitably in a largely rural state and were highly cost-effective, warranting scale-up in other high-mortality rural settings. ISRCTN99422435.


Facile synthesis of metal-chelating magnetic nanoparticles by exploiting organophosphorus coupling.
A new method is described for facile synthesis of metal-chelating magnetic nanoparticles by simply mixing iron oxide nanoparticles with a bifunctional organophosphorus compound, N-(phosphonomethyl)iminodiacetic acid (PM-IDA), in aqueous solution. On charging with nickel ions, the PM-IDA functionalized iron oxide nanoparticles exhibited high His-tag protein binding capacity (0.21 and 0.58 mg/mg for His-tagged green fluorescent protein and chloramphenicol acetyltransferase, respectively) and were successfully used to purify these proteins from bacterial cell extracts to high purity in a single step. Although other synthetic schemes for metal-chelating magnetic nanoparticles have been reported, the method described here is markedly simpler and involves only low-cost reagents.


Risk of Major Mental Disorder after Severe Bacterial Infections in Children and Adolescents: A Nationwide Longitudinal Study.
Evidence has suggested an association between bacterial infection and increased risk of subsequent major mental disorders (MMDs). Whether such association varies with different pathogens remains unclear. We aimed to investigate the risk of subsequent MMDs after exposure to bacterial pathogens in children and adolescents. Between 1997 and 2012, we enrolled a nationwide cohort of 14,024 children and adolescents with hospitalized bacterial infection, and noninfected controls were 1:4 matched for demographics. There were 11 investigated pathogens, namely, Streptococcus, Staphylococcus, Pseudomonas, Klebsiella, Hemophilus, Mycoplasma, Tuberculosis, Meningococcus, Escherichia, Chlamydia, and Scrub typhus. The primary outcomes were the subsequent risk of seven MMDs, namely, autism spectrum disorder (ASD), attention-deficiency hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), tic disorder, schizophrenia, bipolar disorder, and depressive disorder. The secondary outcomes were the subsequent risk of exposure to psychotropic medications. Pooled bacterial infection was associated with increased risk of the six MMDs - ASD (reported as hazard ratios with 95% confidence intervals: 13.80; 7.40-25.75), ADHD (6.93; 5.98-8.03), OCD (3.93; 1.76-8.76), tic disorder (6.19; 4.44-8.64), bipolar disorder (2.50; 1.28-4.86), and depressive disorder (1.93; 1.48-2.51) - and exposure to four psychotropic medications, including ADHD drugs (11.81; 9.72-14.35), antidepressants (2.96; 2.45-3.57), mood stabilizers (4.51; 2.83-7.19), and atypical antipsychotics (4.23; 3.00-5.96) compared to controls. The associations among MMDs and specific pathogens varied. Importantly, Streptococcus was associated with the most MMDs (six MMDs), and ADHD was associated with eight bacterial pathogen infections. After bacterial infection, the risk of MMDs increased in children and adolescents compared to controls, and such associations varied with different pathogens. Future studies are warranted to validate our study findings and investigate the potential mechanisms.


Hepatic microsomal N-demethylation of N-methylbenzamidine. N-dealkylation vs N-oxygenation of amidines.
The microsomal oxidative N-demethylation of N-methylbenzamidine, a model compound for active substances containing the basic amidine function, was investigated. N-Methylbenzamidine was converted into benzamidine and formaldehyde by aerobic incubation with non-induced microsomal fractions of rabbit liver homogenates and NADPH. The formation of benzamidine in the incubation mixtures under widely differing conditions was assayed using a newly-developed, high-performance, ion pair, reverse-phase partition chromatographic method. Optimal reaction conditions were determined. The benzamidine formation in the incubation mixture followed Michaelis-Menten kinetics and required the presence of molecular oxygen and NADPH. The effects of the inducer phenobarbital, methylcholanthrene, ethanol and N-methylbenzamidine itself on the activity were studied. Neither superoxide anion nor hydrogen peroxide was directly involved in the demethylation reaction. The direct involvement of cytochrome P-450 in this reaction is supported by the observation that the presence of inhibitors of cytochrome P-450, in particular of carbon monoxide, markedly decreased the rate of N-demethylation. This N-demethylation of N-methylbenzamidine proves the hypothesis that benzamidines with hydrogen atoms in the alpha-position to the amidine nitrogen atoms are N-dealkylated instead of N-oxygenated by the microsomal mixed function oxidase system.


[The finding of larvae of the taiga tick Ixodes persulcatus (Parasitiformes: Ixodidae) on necrophagous piophilid flies (Diptera: Piophilidae) in the southern Yamal].
In course of mass collecting of necrophilous flies by means of cage traps with a bites of dead small mammals in South Yamal, at latitude 67 North, 3400 dipterans were caught and examined on mite phoresy. Among them two piophilid specimens with two attached Ixodes persulcatus larvae have been recovered.


Paediatric Escherichia coli bacteraemia presentations and high-risk factors in the emergency department.
Escherichia coli (E coli) is a known cause of paediatric bacteraemia. The main objective was to characterise the emergency department (ED) presentations of paediatric E coli bacteraemia and secondarily to identify those related to greater severity. This was a sub-study of a multicentre cross-sectional prospective registry including all with E coli bacteraemia episodes between 2011 and 2016. We used multiple correspondence and cluster analysis to identify different patterns. We included 291 patients and 43 met criteria for severe disease (14.3%, 95% confidence interval 11.2-19.3). We identified four types of paediatric E coli bacteraemia presentations. Two (178 patients, 61.2%) were related to well-appearing previously healthy infants with associated urinary tract infection (UTI). Well-appearing children older than 12 months old with underlying disease (n = 60, 20.6%) and non-well-appearing children of different ages (n = 53, 18.2%) corresponded to the other two types; these had associated UTI infrequently and higher severity rate (15% and 50.9%, respectively, higher when compared with the two previous types, P < .01), including the two patients who died. There were four different types of ED paediatric E coli bacteraemia presentations with different severity. Febrile young children with associated UTI showed the best outcome.


Stent implantation in aorto-ostial lesions: long-term follow-up and predictors of outcome.
To compare the outcomes of drug-eluting (DES) vs. bare-metal (BMS) stents for stenting of native aorto-ostial lesions (AOL) and to identify predictors of major adverse cardio and cerebrovascular events (MACCE). A total of 181 patients (182 AOL) who underwent stenting of AOL were retrospectively identified: right-coronary artery in 130 (71.4%), left main in 52 (28.6%). In-hospital event rate was 1.1% (two non-Q-wave myocardial infarctions). Follow-up was possible in 98.3%, median time=23.9 months (IQR 12.1-37.7). Event rates and survival MACCE-free were not significantly different between DES and BMS. After multivariate analysis, only the logistic EuroSCORE >10% predicted MACCE (HR=4.66, 95% CI: 2.38-9.12, p<0.001), whereas the predictors for TLR were age (HR=0.96, 95% CI: 0.92-1.00, p=0.039) and the stented artery (RCA vs. LM, HR=10.2, 95% CI: 1.37-75.45, p=0.024). AOL stenting can be performed with high success and low complication rates. At follow-up, no significant differences in event rates were found between DES and BMS; EuroSCORE>10% was the only predictor of MACCE.


Narp and NP1 form heterocomplexes that function in developmental and activity-dependent synaptic plasticity.
Narp is a neuronal immediate early gene that plays a role in excitatory synaptogenesis. Here, we report that native Narp in brain is part of a pentraxin complex that includes NP1. These proteins are covalently linked by disulfide bonds into highly organized complexes, and their relative ratio in the complex is dynamically dependent upon the neuron's activity history and developmental stage. Complex formation is dependent on their distinct N-terminal coiled-coil domains, while their closely homologous C-terminal pentraxin domains mediate association with AMPA-type glutamate receptors. Narp is substantially more effective in assays of cell surface cluster formation, coclustering of AMPA receptors, and excitatory synaptogenesis, yet their combined expression results in supraadditive effects. These studies support a model in which Narp can regulate the latent synaptogenic activity of NP1 by forming mixed pentraxin assemblies. This mechanism appears to contribute to both activity-independent and activity-dependent excitatory synaptogenesis.


Injectable cartilage matrix hydrogel loaded with cartilage endplate stem cells engineered to release exosomes for non-invasive treatment of intervertebral disc degeneration.
Low back pain, mainly caused by intervertebral disc degeneration (IVDD), is a common health problem; however, current surgical treatments are less than satisfactory. Thus, it is essential to develop novel non-invasive surgical methods for IVDD treatment. Here, we describe a therapeutic strategy to inhibit IVDD by injecting hydrogels modified with the extracellular matrix of costal cartilage (ECM-Gels) that are loaded with cartilage endplate stem cells (CESCs). After loaded with CESCs overexpressing Sphk2 (Lenti-Sphk2-CESCs) and injected near the cartilage endplate (CEP) of rats in vivo, ECM-Gels produced Sphk2-engineered exosomes (Lenti-Sphk2-Exos). These exosomes penetrated the annulus fibrosus (AF) and transported Sphk2 into the nucleus pulposus cells (NPCs). Sphk2 activated the phosphatidylinositol 3-kinase (PI3K)/p-AKT pathway as well as the intracellular autophagy of NPCs, ultimately ameliorating IVDD. This study provides a novel and efficient non-invasive combinational strategy for IVDD treatment using injectable ECM-Gels loaded with CESCs that express Sphk2 with sustained release of functional exosomes.


Consensus document on controversial issues in the diagnosis and treatment of prosthetic joint infections.
Joint replacement surgery has been on the increase in recent decades and prosthesis infection remains the most critical complication. Many aspects of the primary prevention and clinical management of such prosthesis infections still need to be clarified. The aim of this GISIG (Gruppo Italiano di Studio sulle Infezioni Gravi) working group - a panel of multidisciplinary experts - was to define recommendations for the following controversial issues: (1) Is a conservative surgical approach for the management of prosthetic joint infections effective? (2) Is the one-stage or the two-stage revision for the management of prosthetic joint infections more effective? (3) What is the most effective treatment for the management of prosthetic joint infections due to methicillin-resistant staphylococci? Results are presented and discussed in detail. A systematic literature search using the MEDLINE database for the period 1988 to 2008 of randomized controlled trials and/or non-randomized studies was performed. A matrix was created to extract evidence from original studies using the CONSORT method to evaluate randomized clinical trials and the Newcastle-Ottawa Quality Assessment Scale for case-control studies, longitudinal cohorts, and retrospective studies. The GRADE method for grading quality of evidence and strength of recommendation was applied.


Determination of 17β-estradiol in commercial pasteurized and sterilized milk samples in Mashhad, Iran.
Due to nutritional facts of milk in human life, the quality assessment of dairy products is of the utmost importance. The aim of the current study was to determine the 17β-estradiol level in commercial pasteurized and sterilized milk brands in Mashhad, Iran. In this regard, 160 samples including 80 pasteurized (40 high-fat and 40 low-fat) and 80 sterilized milk (40 high-fat and 40 low-fat) of widely used brands from different supermarkets were collected. The mean level of 17β-estradiol was 8.2 ± 0.59 pg/ml. The mean amount of estradiol was found to be 7.6 ± 0.47, 7.9 ± 0.45, 8.6 ± 0.63, and 8.9 ± 0.54 pg/ml for the low-fat pasteurized, low-fat sterilized, high-fat pasteurized and high-fat sterilized milk, respectively. There was no significant difference between the amount of estradiol in pasteurized and sterilized milk. As expected, the level of estradiol was statistically higher in high fat milks than that of low-fat milks. Considering the levels of 17β-estradiol measured here and the maximum permissible daily level of external estradiol entered to body through edible products recommended by EU and CAC (3.5 µg), at least in the short term, there will be no remarkable impact on the endocrine system. However, judging the long-term effects of using these products is not easy and simple at all, as cancers develop during a long period of time and has a multifactorial etiology.


Analysis of the dislocation activity of Mg-Zn-Y alloy using synchrotron radiation under tensile loading.
An understanding of deformation behavior and texture development is crucial for the formability improvement of Mg alloys. X-ray line profile analysis using the convolutional multiple whole profile (CMWP) fitting method allows the experimental determination of dislocation densities separately for different Burgers vectors up to a high deformation degree. A wider use of this technique still requires exploration and testing of various materials. In this regard, the reliability of the CMWP fitting method for Mg-Zn-Y alloys, in terms of the dislocation activity during tensile deformation, was verified in the present study by the combined analysis of electron backscatter diffraction (EBSD) investigation and visco-plastic self-consistent (VPSC) simulation. The predominant activity of non-basal 〈a〉 dislocation slip was revealed by CMWP analysis, and Schmid factor analysis from the EBSD results supported the higher potential of non-basal dislocation slip in comparison with basal 〈a〉 dislocation slip. Moreover, the relative slip activities obtained by the VPSC simulation also show a similar trend to those obtained from the CMWP evaluation.


Removal of selected emerging PPCP compounds using greater duckweed (Spirodela polyrhiza) based lab-scale free water constructed wetland.
Greater duckweed (Spirodela polyrhiza) based lab-scale free water constructed wetland (CW) was employed for removing four emerging pharmaceuticals and personal care products (PPCPs) (i.e. DEET, paracetamol, caffeine and triclosan). Orthogonal design was used to test the effect of light intensity, aeration, E.coli abundance and plant biomass on the target compounds. Synthetic wastewater contaminated with the target compounds at concentration of 25 μg/L was prepared, and both batch and continuous flow experiments were conducted. Up to 100% removals were achieved for paracetamol (PAR), caffeine (CAF) and tricolsan (TCS) while the highest removal for DEET was 32.2% in batch tests. Based on orthogonal Duncan analysis, high light intensity (240 μmolmm-2s-1), full aeration, high plant biomass (1.00 kg/m2) and high E.coli abundance (1.0 × 106 CFU/100 mL) favoured elimination of the PPCPs. Batch verification test achieved removals of 17.1%, 98.8%, 96.4% and 95.4% for DEET, PAR, CAF and TCS respectively. Continuous flow tests with CW only and CW followed by stabilization tank (CW-ST) were carried out. Final removals of the PPCP contaminants were 32.6%, 97.7%, 98.0% and 100% for DEET, PAR, CAF and TCS, respectively, by CW system alone, while 43.3%, 97.5%, 98.2% and 100%, respectively, were achieved by CW-ST system. By adding the ST tank, PPCP concentrations decreased significantly faster (p < 0.05) compared with continuous flow CW alone. In addition, after removing aerators during continuous flow CW experiments, the treatment systems presented good stability for the PPCP removals. CW-ST showed better chemical oxygen demand (COD) and total organic carbon (TOC) removals (89.3%, 91.2%, respectively) than CW only (79.4%, 85.2%, respectively). However, poor DEET removal (<50%) and high E.coli abundance (up to 1.7 log increase) in the final treated water indicated further treatment processes may be required. Statistical analysis showed significant correlations (p < 0.05) between PPCPs and water quality parameters (e.g. COD, nitrate, phosphate), and between the four PPCP compounds for the continuous flow CW and CW-ST systems. Positive results encourage further test of Greater duckweed at pilot scale CW using real wastewater.


Answering multiple-choice questions in high-stakes medical examinations.
To examine whether changing initial answers during a multiple-choice question (MCQ) test in medicine brings about better overall test results, as has been shown in other academic fields. A total of 36 answer books from the German Second National Medical Board Examination, with 580 MCQs (where 1 answer out of 5 must be selected), were used for analysis. We confirmed that high-stakes MCQ test scores in medicine did indeed improve when students changed their answers once. Further changes of answers did not improve the scores. In written, high-stakes medical examinations, we recommend that students be encouraged, after further reflection, to change their answers in MCQ tests for questions for which they had previously had doubts about the answers.


Uninfected but not unaffected: chronic maternal infections during pregnancy, fetal immunity, and susceptibility to postnatal infections.
Chronic infections during pregnancy are highly prevalent in some parts of the world. Infections with helminths, Trypanosoma cruzi, Plasmodium spp, and HIV might affect the development of fetal immunity and susceptibility to postnatal infections independently of in-utero transmission of the pathogens. Fetal adaptive immune responses are common in neonates who have been exposed to maternal infection during pregnancy but not infected themselves. Such responses could affect the development of immunity to the homologous pathogens and their control during the first few years of life. Fetal innate and regulatory responses might also affect immunity to unrelated pathogens and responses to vaccines. Strategies to improve child health should integrate the possible clinical implications of in-utero exposure to chronic maternal infections.


Speed of sound in bone at the tibia: is it related to lower limb bone mineral density in spinal-cord-injured individuals?
A cross-sectional study evaluating BMD at the hip and tibia, and SOS at the radius and mid-tibia in individuals with spinal cord injury (SCI) and a subgroup of non-SCI individuals. To investigate the speed of sound (SOS) in bone in relation to bone mineral density (BMD). Kinesiology Department, McMaster University, Ontario, Canada. In 14 individuals with SCI and 10 non-SCI individuals, proximal femur and tibia BMD were measured using dual energy X-ray absorptiometry, and radius and tibia SOS were measured with an ultrasonometer. T-scores were calculated using healthy reference databases. Inter-relationships between measurement techniques were determined using Pearson's correlation coefficients. P-values less than 0.05 were considered statistically significant. : The average ages of the SCI and non-SCI groups were 33+/-9 and 27+/-6 years, respectively. Lesion level ranged from C4 to T12 and average time postinjury was 12 years, with a range of 1.6-25 years. Using the WHO criteria for osteoporosis, nine of 14 SCI subjects were osteoporotic at the hip, with the remainder in the osteopenic range. Tibia SOS T-scores were in the osteoporotic range for one subject with SCI, and two were in the osteopenic range. Among non-SCI individuals, one male had a tibia SOS T-score of -1.4, all others were within the normal range. Hip BMD and tibia SOS were significantly correlated (r=0.46, P<0.01). Hip BMD and tibia BMD were more strongly correlated (r=0.80, P<0.0005). Tibia BMD was not significantly correlated with SOS at the tibia (r=0.35, P=0.09). Radius SOS T-scores were positive and not significantly correlated with any lower limb variable. Lower-limb bone mass is reduced in spinal cord-injured individuals, but SOS at the mid-tibia is not. It remains to be determined whether ultrasound measurements can predict fracture in the SCI population.


The two "faces" of Antillean prostitution.
Prostitutes who operate in the refinery town of St. Nicholas, the second largest urban center in Aruba, Netherlands Antilles, fall into two categories: temporary migrants from Colombia, who live and work for 3-month periods in the saloon-cribs along the main street; and permanently resident Dominican Republicans, who live and work in the village ghetto. The Colombians receive encomia, the Dominican Republicans, opprobria. In addition to addressing the differential statuses, prognoses, and earnings of the two groups, this paper also examines the historical background to the development of the differential assessments and offers ethnographic support for the continuation of the structural oppositions that separate the two groups. It is suggested that local perceptions of "other" people (including prostitutes) are tied to specific social and economic circumstances. Variables such as economic competition, ethnicity, length of employment in a low-status occupation, and the generally favored position accorded to "people like us," in contrast to the negative attitude held toward "people like them," are examined in terms of their relevance to the differential status of the two groups. It is also suggested that the underlying as well as the overt bases for these stereotypical ascriptions may have broader applicability: differential rather than unilateral assessments may indeed be the norm rather than a peculiarly Antillean perception.


Onchocercal lymphadenitis: Clinicopathologic study of 34 patients.
Clinicopathological studies on lymph nodes of 32 Africans with onchocerciasis--some complicated by hanging groin and elephantiasis of the genitalia--revealed atrophic lymphoid tissue, lymphoedema, chronic inflammation and fibrosis. We identified microfilariae of Onchocerca volvulus in nodes of 24 of 32 Africans (75%). There microfilariae were most numerous in the capsule and in the fibrous tissue of the medulla, but smaller numbers were also found within lymphoid tissue, in dilated lymphatics and in blood vessels. We believe that in Africians, antigens released from microfilariae of O. volvulus lead to the deposition of immune complex in tissues, which in turn causes inflammation and fibrosis and eventually obstructive lymphadenitis. This causes hanging groin and, possibly, also elephantiasis. A distinctive pattern of perivascular fibrosis contains "fibrinoid material" that we interpret as immune complexes involving microfilarial antigens. In contrast, nodes from two Yemenites with severe onchocercal dermatitis of the lower limbs (sowda) had hyperplastic follicles, minimal fibrosis and no microfilariae.


Sexual and reproductive health of Syrian refugee women in Turkey: a scoping review within the framework of the MISP objectives.
Turkey hosts the world's largest community of Syrians displaced by the conflict. The Minimum Initial Service Package (MISP) is a coordinated set of priority reproductive health services. There is not any scoping review assessing the RH situation of Syrian refugees in Turkey within the framework of the MISP objectives. The objectives of this review is to identify the situation of sexual and reproductive health (SRH) among Syrian refugee women in Turkey, and document the health services provided for them in terms of the components of MISP. We hoped to show evidence of gaps and help guide future research to focus on priority areas to improve the range, quality, and access to SRH services and to recommend public health interventions. The literature search was conducted in Turkish and English. Multiple electronic databases (Turkish Medline, Google Scholar, PubMed, Web of Science, Medline, Cochrane Database of Systematic Reviews, EBSCOHost, CINAHL, and Embase) were searched from January 2011 to May 2018. References published in the peer-reviewed literature, the grey-literature, and on websites were eligible for inclusion if they had conducted research on one or more of the following SRH topics specifically for Syrian women in Turkey: maternal and neonatal health/antenatal care, HIV and sexually transmitted infections, use of contraceptives, sexual violence, and services delivery and accessibility. References were excluded if any of the following criteria were relevant: not specific to Syrian women refugees in Turkey. Firstly, the titles and abstracts of the articles that were found were examined to determine if they met the eligibility criteria. Secondly, if the abstracts and titles met one or more of the eligibility criteria, the full text of the articles have been examined. Finally, standard forms were prepared and used to summarize the articles narratively. The results of the screening were recorded in Excel spreadsheets for comparison, and any disagreements among the researchers were resolved by consensus. The studies were grouped according to the MISP objectives. A total of 24 publications were eligible for inclusion in the review. Consanguineous marriage rate was 56%. The rate of marriage under age 18 were very high. Mean age at first marriage was found to be between 18 and 20. The rate of antenatal care was inadequate. The rate of using a modern contraceptive method was 24% among married and all age groups of Syrian women. The rates of unmet family planning needs were about 35%. Among patients admitted to gynecology outpatient clinics, about half of the applicants were reported to have abnormal vaginal discharge. The reported rates of sexual violence were about 8%. Only 20% of Syrian women had regular gynecological visits. Overall, we conclude that early marriage, low modern contraceptive use, unmet need for contraception, sexual and gender-based violence are the major SRH issues reported. There is a need for further studies to identify the barriers limiting service uptake as well as to document successful practices. Long term strategies to improve the SRH status of Syrian refugee women should be developed with participation of all stakeholders. This review is significant in terms of that it is the first scoping review assessing the RH situation of Syrian refugees in Turkey within the framework of the MISP objectives. Based on the data of this review, relevant policy makers should consider to improve the SRH status of Syrian women refugees in Turkey.


Sudden transient complete loss of vision caused by nose blowing after a fracture of the orbital floor.
A 52-year-old man was being attended to in a hospital for a fracture of the right zygoma and orbital floor, after being struck on the right upper face. After blowing his nose, he immediately lost vision in the right eye, and an urgent CT scan showed extensive retrobulbar air. Vision was regained within an hour. The management of this rare condition is discussed.


[Determination of melamine by high-performance liquid chromatography-mass spectrometry in urinary calculi].
To establish a high-performance liquid chromatography-mass spectrometry (LC/MS)-based method for efficient determination of melamine in urinary calculi in children taking melamine-contaminated formula milk powder. LC/MS was employed to determine the contents of melamine in urinary calculi surgically removed from 17 children with a history of taking melamine-contaminated milk powder and in 4 samples of uric acid stone from adults. The positive ionization mode of electro-spray ionization source was used, and the limit of melamine determination was 0.1 mg/kg. No melamine was detected in the 4 uric acid stone samples from adults. Melamine was detected in 4 samples of urinary calculi from the 17 children, with the concentration ranging from 0.8 to 64 mg/lkg. LC/MS is simple and effective for detecting melamine in urinary calculi, which is helpful to the treatment and follow-up.


A comparison of the accuracies of clinical and radiological assessment of gestational age.
The accuracy of radiological and clinical assessment of gestational age was compared in a retrospective survey. The radiological assessment was found to be only marginally more accurate than clinical assessment.


REM sleep behavior disorder in Japanese patients with Parkinson's disease: a multicenter study using the REM sleep behavior disorder screening questionnaire.
REM sleep behavior disorder (RBD) is known to be observed more frequently in patients with an α-synucleinopathy such as Parkinson's disease (PD) than in the general population. The precise prevalence of RBD in Japanese PD patients is not known. Therefore, we investigated the prevalence and the clinical characteristics of patients with RBD in a large population of Japanese patients with PD. We investigated various clinical features and employed the Japanese version of the RBD screening questionnaire on 469 non-demented Japanese PD patients in this multicenter study. Probable or possible RBD was detected in 146 patients (31.1%) and was significantly associated with longer PD duration, higher Hoehn and Yahr stage, higher Unified Parkinson's Disease Rating Scale part III subscale (7 items), more motor fluctuations, and a higher levodopa-equivalent daily dose (p < 0.01). As to the major autonomic dysfunctions, severe constipation was significantly more frequent in PD patients with RBD than in those without it (p < 0.01). The RBD symptoms of 53 patients (39.0%) preceded the onset of PD motor symptoms. The median interval from the onset of RBD symptoms to PD motor symptoms was 17.5 years, and 3 patients had intervals of over 50 years. This large-scale multicenter study revealed that RBD is a frequent non-motor symptom in Japanese patients with PD, which may precede the onset of motor symptoms. Moreover, RBD that increases with the duration and severity of PD may be associated with autonomic dysfunction.


Iron storage in Saccharomyces cerevisiae.
A ferritin-like molecule was purified from iron-loaded cells of Saccharomyces cerevisiae, but its iron content was very low and was not representative of the cellular iron content. A study of the intracellular distribution of iron has shown that the vacuoles are involved in the storage of iron in the yeast cell. Moreover, it seems that this vacuolar iron can be further utilised by the cells for iron-requiring processes such as mitochondriogenesis.


Not in their hands only: hospital hygiene, evidence and collective moral responsibility.
Hospital acquired infections (HAIs) are a major threat to patient safety. This paper addresses the following question: given what is known about the causes of and possible interventions on HAIs, to whom or what should the moral responsibility for preventing these infections be attributed? First, we show how generating robust evidence on the effectiveness of preventive hygiene measures is a complex endeavour and review the existing evidence on the causes of HAIs. Second, we demonstrate that the existing literature on the ethical aspects of infection control has focused on responsibility at the individual-level. Thirdly, we argue that these accounts do not accommodate systemic factors relevant for HAI prevention. We show that the notion of collective responsibility is useful for making understandable how systemic factors, such as employment conditions in hospitals, are both causally and ethically relevant in infection control.


Potassium-titanyl-phosphate laser photoselective vaporization for benign prostatic hyperplasia: 5-year follow-up from a district general hospital.
The 80-W potassium-titanyl-phosphate (KTP) laser photoselective vaporization of the prostate (PVP) is a minimally invasive surgical option for patients with symptomatic benign prostatic hyperplasia, although evidence of long-term efficacy is limited. We present the long-term outcomes from a heterogeneous patient population. We prospectively collected data for all patients who underwent 80-W KTP laser PVP treatment between 2004 and 2005. Evaluation occurred pr-operatively, and then at 3, 6, 12, and 60 months postoperatively. This included International Prostate Symptom Score (IPSS), peak urinary flow rate (Qmax), postvoid residual (PVR) volume, serum prostate-specific antigen measurement, and transrectal ultrasonography-estimated prostate volume. A total of 115 patients were eligible for analysis, with a mean age of 77 years and mean prostate volume of 55.8 cc. Of these, 74% were operated on for lower urinary tract symptoms, 23% for acute urinary retention, and 3% for chronic retention; 30% of patients were American Society of Anesthesiologists score ≥ 3, and 93% were treated as 23-hour stays. No patients needed blood transfusion, and there were no cases of transurethral resection syndrome. An initial trial-without catheter failed in 11 (9.6%), although 8 of these successfully voided after a further week. At 5-year follow-up, mean Qmax improved from 8.0 ± 5.0 mL to 13.9 ± 7.7 mL and mean IPSS improved from 22 ± 5 to 9 ± 7. There were no cases of urethral strictures, but there was a 3.3% rate of bladder neck stenosis and an overall re-treatment rate of 21% over 5 years. We confirm the long-term durability of the 80-W KTP laser PVP with minimal perioperative morbidity. It is therefore a safe option for high-risk patients with medical comorbidities, although its high reoperation rate may limit its use to this specific patient population.


Desensitization of rat mast cells: studies of some effects of anti-allergic drugs.
Peritoneal mast cells from rats immunized with dinitrophenylated ovalbumin (DNP-OA) or normal cells passively sensitized with mouse anti-DNP-OA were incubated in vitro with DNP-bovine serum albumin in the absence of Ca++. This procedure induced desensitization of the cells, such that histamine release was inhibited on subsequent challenge with OA, in the presence of Ca++. The phenomenon of desensitization is supposed to involve early stages in the histamine release process and, thus, two anti-allergic drugs, disodium cromoglycate and doxantrazole, which inhibit an early event(s), were added with the Ca++ -free antigen to investigate whether they had any effect on desensitization. The inhibition of final histamine release caused by each drug and that due to desensitization were approximately additive. It was concluded that the drugs did not influence desensitization of rat mast cells. Thus, their activity was consistent with an effect on an event in the histamine release process, occurring after the generation of the activated stage believed to be responsible for desensitization.


[Radiation dose to patients and informativeness of the images obtained during eye examinations using x-ray computed tomography].
Reducing the scanning time and the X-ray tube anode current to 80-100 mA is the main way of reducing the radiation dose without noticeably lowering the tomogram image quality in examination of the eye area using the USA QUAD-1 X-ray computer tomograph of the fourth generation. The optimum tube voltage is 140 kW. Narrowing the collimator slit and reducing the number of sections can also lower the total radiation dose, but these measures are less universal for they are determined by clinical situation.


Evaluation of a new pulse oximeter testing device.
Valid routine testing of pulse oximeters and their sensors is problematic. A suitable testing device must not only generate the pulsatile signal the pulse oximeter requires for its operation, but must possess light absorption characteristics similar to those of living tissue. A new device called Pulse Oximeter Tester (POT) has recently become available which, it is claimed, addresses these problems. To evaluate the POT as a suitable stimulus for pulse oximeters. We tested all the pulse oximeters and their sensors with a set of POTs simulating blood oxygen saturation of 80%, 90% and 100%. The tests were performed at simulated heart rates of 30, 75 and 110 bpm. The SpO2 readings (mean +/- SD) obtained with the 80%, 90% and 100% POTs were 80.7 +/- 1.3%, 90.3 +/- 0.9% and 100 +/- 0.0% respectively. There were no significant differences in readings obtained at the different simulated heart rates. Two pulse oximeters gave readings that deviated more than 2 SD from the mean. Their sensors were subsequently found to be defective. POTs provide suitable stimuli for testing pulse oximeters. In our study sample they were found to be highly specific, but of unknown sensitivity.


Safety of cyanoacrylate-based adhesives in creating layered septal cartilage grafts during open structure septorhinoplasty.
Patients having suffered severe nasal trauma or having undergone prior septal surgery present particular problems during open structure septorhinoplasty. Septal cartilage deficient noses often require costal or conchal cartilage grafting or the use of allograft material, resulting in secondary donor site morbidity, longer operative times and variable results. The present study evaluated the utility of cyanoacrylate-based adhesives (CBA) in creating layered septal cartilage grafts from remnant septal cartilage for L-strut reconstruction during open septorhinoplasty. A retrospective clinical review was performed at a university-based facial plastic and reconstructive surgical practice, identifying patients undergoing open structure septorhinoplasty performed by the senior authors. Procedures involved construction of a layered caudal or dorsal L-strut graft from at least two smaller autologous septal cartilage grafts. The grafts were adhered together with CBA with 5-0 polydioxanone suture (Ethicon, Somerville, NJ) used for reinforcement. Stability of the final construct was assessed postoperatively. Fifteen patients were included with mean age of thirty-nine years (range: 15-65). Fifty-three percent of the patients had undergone prior nasal surgery: Seven had undergone at least one prior external septorhinoplasty and one had undergone prior endonasal septoplasty. Median follow-up was 144 days (range: 45-405). Postoperatively, one local infection was noted and two patients complained of post-operative columellar deviation. No other complications were encountered. CBAs provide a safe technique in the crafting of layered grafts to provide reliable tip/dorsal support when performing open structure septorhinoplasty among patients with cartilage deficient or severely traumatized septa.


Expanding the spectrum of germline variants in cancer.
Our ability to identify germline variants in hereditary cancer cases remains challenged by the incomplete cataloging of relevant genes and lack of consensus on who should be tested. We designed a panel [hereditary oncogenesis predisposition evaluation (HOPE)] that encompasses most of the genes known to be associated with cancer development and tested its yield on more than 1300 samples of cancer patients. Pathogenic or likely pathogenic variants in high and intermediate risk genes were identified in 16, 23.9, 9.7 and 2.7%, respectively, of peripheral blood or normal tissue samples taken from patients with breast, ovarian, colorectal and thyroid cancer. To confirm specificity of these findings, we tested an ethnically matched cohort of 816 individuals and only identified pathogenic or likely pathogenic variants in 1.59% (0.98% in high risk and 0.61% in intermediate risk). Remarkably, pathogenic or likely pathogenic alleles in DNA repair/genomic instability genes (other than BRCA2, ATM and PALB2) accounted for at least 16.8, 11.1, 50 and 45.5% of mutation-positive breast, ovarian, thyroid and colorectal cancer patients, respectively. Family history was noticeably lacking in a substantial fraction of mutation-positive cases (63.7, 81.5, 42.4 and 87.5% in breast, ovarian, colorectal and thyroid, respectively). Our results show high contribution of germline mutations to cancer predisposition that extends beyond "classical" hereditary cancer genes. Family history was lacking in 63.5% mutation-positive cases, shows that hereditary cancer need not appear familial and suggests that relaxed selection of cancer patients for hereditary cancer panels should be considered.


Epidural capsaicin produces prolonged segmental analgesia in the rat.
The effect of epidural capsaicin injections on the thermal nociceptive threshold of unrestrained freely moving adult rats was examined. Capsaicin solution (1% 0.05 ml, 0.1 ml) was injected in a single dose or in two consecutive doses through an indwelling lumbar epidural catheter. Effects were compared with 1 ml 1% capsaicin injected intraperitoneally. Twelve rats served as sham-treated and vehicle controls. Nociceptive thermal stimuli were brief pulses of CO2 laser radiation directed at three body areas, hind limb, forelimb, and pinna. Capsaicin caused prolonged, segmental thermal analgesia. Maximal nociceptive threshold values in the hind limbs, attained within 24 h of epidural injection, were 2.5 (P less than or equal to 0.006) and 5.3 (P less than or equal to 0.0005) time control values for the 0.05-ml and 0.1-ml doses, respectively. Response thresholds in the forelimbs and pinna were unaffected. Two-stage epidural injection of capsaicin led to a roughly twofold elevation of threshold, as well as prolongation of the analgesia to about 14 days. Intraperitoneal injection of capsaicin resulted in elevation of nociceptive threshold which included all body areas tested. These results indicate that epidural application of capsaicin at the lumbar spinal level produced a profound and long-lasting segmental analgesia.


Gastroscopic-assisted laparoscopic wedge resection of B-cell gastric mucosa-associated lymphoid tissue (MALT) lymphoma.
Helicobacter pylori has been implicated as an etiologic agent for B-cell gastric mucosa-associated lymphoid tissue (MALT) lymphoma. This tumor is considered a low-grade entity with an associated indolent course. Some instances of tumor regression with adequate antibiotic treatment and irradication of H. pylori have been reported. Gastric malignancy and more specifically, lymphoma, should be considered in all patients with recurrent or nonhealing ulcers. Diagnostic and treatment strategies for these patients remain controversial. Two patients were evaluated, one for recurrent disease, another for a 3-cm nonhealing ulcer. Both patients refused total gastrectomy. Both patients underwent gastroscopy with simultaneous laparoscopic visualization. The mucosal lesions were identified and removed via laparoscopic stapled wedge resection. A combined endoscopic and laparoscopic approach can be considered as an alternative to radical surgery in the treatment strategy of these tumors. Wedge resection allows for staging and thorough pathologic classification. Further studies are necessary to define the natural history and the role of laparo-endoscopy in the diagnosis, staging, and treatment of B-cell gastric MALT lymphoma.


Cholera toxin induces maturation of human dendritic cells and licences them for Th2 priming.
Cholera toxin (CT) is a potent mucosal adjuvant that amplifies B and T cell responses to mucosally co-administered antigens, stimulating predominant Th2-type responses. However, little is known about the mechanism of adjuvanticity of CT and on the influence this toxin may have on Th2 cell development during the priming of an immune response. We analyzed the effect of CT on dendritic cells (DC), which are responsible for the priming of immune responses at the systemic as well as at the mucosal level. We found that CT induces phenotypic and functional maturation of blood monocyte-derived DC. Indeed, CT-treated DC up-regulate expression of HLA-DR molecules, B7. 1 and B7.2 co-stimulatory molecules, and are able to prime naive CD4(+)CD45RA(+) T cells in vitro, driving their polarization towards the Th2 phenotype. Furthermore, CT-matured DC express functional chemokine receptors CCR7 and CXCR4 which may render them responsive to migratory stimuli towards secondary lymphoid organs. Interestingly, the maturation program induced by CT is unique since CT does not induce but rather inhibits cytokine (IL-12p70 and TNF-alpha) and chemokine (RANTES, MIP-1alpha and MIP-1beta) secretion by lipopolysaccharide- or CD40 ligand-activated DC. Our results help to elucidate the mechanism of action of CT as an adjuvant and highlight a new stimulus of bacterial origin that promotes maturation of DC.


Prevalence, risk factors, and potential symptoms of hyponatremia after spinal surgery in elderly patients.
Old age and spinal surgery significantly increase the risk of postoperative hyponatremia. However, detailed analyses of postoperative hyponatremia after spinal surgery in elderly patients are lacking. Therefore, we retrospectively reviewed the records of 582 consecutive patients aged > 60 years who underwent spinal surgery to evaluate the frequency, risk factors, and symptoms of postoperative hyponatremia after spinal surgery in the elderly population. Postoperative hyponatremia was defined as a postoperative blood sodium level < 135 meq/L at postoperative day (POD)1, POD3, and/or after POD6. A total of 92 (15.8%) patients showed postoperative hyponatremia. On a multivariate analysis, a diagnosis of a spinal tumor/infection, decompression and fusion surgery, and lower preoperative sodium levels were significant independent factors of postoperative hyponatremia (p = 0.014, 0.009, and < 0.001, respectively). In total, 47/92 (51%) cases could have been symptomatic; vomiting was noted in 34 cases (37%), nausea in 19 cases (21%), headache in 14 cases (15%), and disturbances in consciousness, including delirium, in ten cases (21%); all incidences of these symptoms were significantly higher in elderly patients with postoperative hyponatremia than in the matched control group without postoperative hyponatremia (p < 0.05, respectively). Additionally, the length of stay was 2 days longer in patients than in the matched controls (p = 0.002).


Immunoelectrophoretic evidence of a thrombin-induced abnormality in a new variant of hereditary dysfunctional antithrombin III (AT III 'Vicenza').
An Italian family with thrombosis and hereditary dysfunctional AT III, i.e. reduced biological activity and normal levels of the immunoreactive protein is presented. The abnormal molecule, called AT III 'Vicenza', was characterized by two-dimensional crossed immunoelectrophoresis either in the absence or presence of heparin. In the presence of heparin, a normal pattern was found in plasma, but abnormality was evident in serum. A similar abnormality was found in plasma artificially clotted with thrombin. The role of thrombin in inducing the immunoelectrophoretic abnormality of AT III 'Vicenza' is discussed.


Element Levels and Predictors of Exposure in the Hair of Ethiopian Children.
Children's development and health may be affected by toxic heavy metal exposure or suboptimal essential element intake. This study aimed to provide updated information regarding the concentrations of 41 elements in children's hair (aged under 18) living in a rural area of the Benishangul-Gumuz region, Ethiopia. The highest average levels (as a geometric mean) for toxic heavy metals were obtained for Al (1 mg kg-1), Pb (3.1 mg kg-1), and Ni (1.2 mg kg-1), while the lowest concentrations among the essential elements were found for Co (0.32 mg kg-1), Mo (0.07 mg kg-1), Se (0.19 mg kg-1), and V (0.8 mg kg-1). Hair analysis was combined with a survey to evaluate relationships and variations among subgroups and potential metal exposure predictors. Females showed significantly higher concentrations for most hair elements, excluding Zn, than males, and the 6-11 years age group reported the highest levels for Be, Ce, Co, Fe, La, Li, Mo, and Na. The main predictors of exposure to toxic elements were fish consumption for Hg and drinking water for Ba, Be, Cs, Li, Ni, Tl, and U. The data from this study can be used to develop prevention strategies for children's health and protection in developing countries.


Leukotrienes C and D induce bronchoconstriction in man.
Pulmonary responses to aerosols of synthetic leukotrienes C and D were examined in two normal volunteers. The leukotrienes were equipotent and equieffective in producing moderate bronchoconstriction accompanied by coughing. Changes in FEV1 were slight, but changes in expiratory flow at low lung volumes were more notable. FPL 55712 abolished the cough response and partially inhibited the bronchoconstriction.


Physiologic benefits of rate responsiveness.
Increases in metabolic demand in response to routine activities and exercise are met through greater cardiac output and oxygen delivery. Patients with fixed-rate pacemakers cannot increase heart rate and must rely solely on increases in stroke volume to provide the necessary adjustments in cardiac output. These compensatory stroke volume increases limit the fixed-rate pacemaker patient's ability to meet the demand of their daily routine. A physiological, rate responsive pacemaker was studied and it was found to increase maximum exercise tolerance from 4.4 +/- .62 METS paced VVI at 65 ppm to 8.1 +/- .71 METS when the same patients were paced rate responsively at an average rate of 91 +/- 3.8 ppm. Animal studies were used to quantify the limitation in stroke volume reserve. Maximum increases of 55.8 +/- 3.7% over resting values were seen in animals in complete heart block at pacing rates of 100 ppm during strenuous exercise. Higher pacing rates increased cardiac output at the same exercise intensity, from 4.94 +/- .72 lpm at 100 ppm to 7.66 +/- 1.02 lpm at 250 ppm. A pacemaker that increases pacing rate in response to greater metabolic demand will maintain stroke volume and end-diastolic volume at near normal values while providing significant improvement in cardiac output and work capacity.


Prenatal detection of de novo paracentric inversion 46, XX inv (14) (q22q32.1) in a normal child: report and review of the literature.
We present prenatal diagnosis and follow-up examination of an individual with a de novo paracentric inversion of the long are of chromosome 14. A literature search documented 19 other cases of paracentric inversion of 14q. The outcome of each of these cases is specified together with that of this current case. Four of the 20 cases, all XY, manifested significant abnormalities with mental retardation and microcephaly present in 3 of the 4 cases; 15% (2/13) of familial cases had abnormalities and 40% (2/5) of de novo cases had abnormalities.