Micro-nanofiber composite biomimetic conduits promote long-gap peripheral nerve regeneration in canine models.
Peripheral nerve injuries may result in severe long-gap interruptions that are challenging to repair. Autografting is the gold standard surgical approach for repairing long-gap nerve injuries but can result in prominent donor-site complications. Instead, imitating the native neural microarchitecture using synthetic conduits is expected to offer an alternative strategy for improving nerve regeneration. Here, we designed nerve conduits composed of high-resolution anisotropic microfiber grid-cordes with randomly organized nanofiber sheaths to interrogate the positive effects of these biomimetic structures on peripheral nerve regeneration. Anisotropic microfiber-grids demonstrated the capacity to directionally guide Schwann cells and neurites. Nanofiber sheaths conveyed adequate elasticity and permeability, whilst exhibiting a barrier function against the infiltration of fibroblasts. We then used the composite nerve conduits bridge 30-mm long sciatic nerve defects in canine models. At 12 months post-implant, the morphometric and histological recovery, gait recovery, electrophysiological function, and degree of muscle atrophy were assessed. The newly regenerated nerve tissue that formed within the composite nerve conduits showed restored neurological functions that were superior compared to sheaths-only scaffolds and Neurolac nerve conduit controls. Our findings demonstrate the feasibility of using synthetic biophysical cues to effectively bridge long-gap peripheral nerve injuries and indicates the promising clinical application prospects of biomimetic composite nerve conduits.


Metabolism of 17alpha-hydroxyprogesterone caproate by hepatic and placental microsomes of human and baboons.
Recent data from our laboratory revealed the formation of an unknown metabolite of 17 hydroxyprogesterone caproate (17-HPC), used for treatment of preterm deliveries, during its perfusion across the dually perfused human placental lobule. Previously, we demonstrated that the drug is not hydrolyzed, neither in vivo nor in vitro, to progesterone and caproate. Therefore, the hypothesis for this investigation is that 17-HPC is actively metabolized by human and baboon (Papio cynocephalus) hepatic and placental microsomes. Baboon hepatic and placental microsomes were investigated to validate the nonhuman primate as an animal model for drug use during pregnancy. Data presented here indicate that human and baboon hepatic microsomes formed several mono-, di-, and tri-hydroxylated derivatives of 17-HPC. However, microsomes of human and baboon placentas metabolized 17-HPC to its mono-hydroxylated derivatives only in quantities that were a fraction of those formed by their respective livers, except for two metabolites (M16' and M17') that are unique for placenta and contributed to 25% and 75% of the total metabolites formed by human and baboon, respectively. The amounts of metabolites formed, relative to each other, by human and baboon microsomes were different suggesting that the affinity of 17-HPC to CYP enzymes and their activity could be species-dependent.


Genetic analysis of a Treponema phagedenis locus encoding antigenic lipoproteins with potential for antigenic variation.
Digital dermatitis (DD) is a painful and debilitating claw disease in cattle. Spirochetes of the genus Treponema are found in high numbers in the lesions and are likely to be involved in the pathogenesis. The occurrence of Treponema phagedenis in DD lesions, especially near the interface of healthy and diseased tissue, suggests that this species contributes to the development and/or progression of the lesions. In this study we characterized a genetic locus in T. phagedenis that contains coding regions for three antigenic proteins, PrrA, VpsA, and VpsB. Comparative analysis of homologous loci from fifteen strains suggests that prrA may be transposed into or out of this locus. Alterations in the copy number of TA repeats within the putative promoter region may regulate VpsA/B expression. The vpsA and prrA genes occur in allelic variants in different T. phagedenis isolates and may provide one explanation for the antigenic variation observed in T. phagedenis DD isolates.


SaOS-2 cell response to macro-porous boron-incorporated TiO2 coating prepared by micro-arc oxidation on titanium.
The aims of the present study were to develop boron-incorporated TiO2 coating (B-TiO2 coating) through micro-arc oxidation (MAO) and subsequently evaluate the effect of boron incorporation on the in vitro biological performance of the coatings. The physicochemical properties of B-TiO2 coating and its response to osteoblast like cells (SaOS-2) were investigated compared to the control group without boron (TiO2 coating). The morphological and X-ray diffraction results showed that both coatings exhibited similar surface topography and phase composition, respectively. However, the incorporation of B led to an enhancement in the surface hydrophilicity of B-TiO2 coating. The spreading of SaOS-2 cells on B-TiO2 coating was faster than that on TiO2 coating. The proliferation rate of SaOS-2 cells cultured on B-TiO2 decreased after 5days of culture compared to that on TiO2 coating. SaOS-2 cells cultured on B-TiO2 coating exhibited an enhanced alkaline phosphatase (ALP) activity, Collagen I synthesis and in vitro mineralization compared to those on TiO2 coating. The present findings suggest that B-TiO2 coating is a promising candidate surface for orthopedic implants.


The characteristics of mobile families with young children in England and the impact of their moves on neighbourhood inequalities in maternal and child health.
This study compares the health and socio-demographic characteristics of residentially mobile families with young children in England to families that do not move and assesses the impact of their moves upon inequalities in health between neighbourhoods. The analysis uses data from the first two waves of the Millennium Cohort Study describing 9022 cohort members, born in 2000-2002, and their families. A third of the families moved between the waves of the survey when the children were aged nine months and three years. Mobile families moved disproportionately toward less deprived areas but had disadvantaged socio-economic characteristics and poor outcomes for infant's birth weight and accidents and mother's self-rated health, limiting longstanding illness and mental health. Health outcomes were worst among the minority moving to more deprived neighbourhoods. Families' moves moderately increased health inequalities between neighbourhoods with high and low deprivation.


The enhancement in toxic potency of oxidized functionalized polyethylene-microplastics in mice gut and Caco-2 cells.
Microplastics (MPs) are inevitably oxidized in the environment, however, to date, no studies have discussed the biological toxicity of oxidized polyethylene (Ox-PE) MPs. In this study, oxidized low-density polyethylene (Ox-LDPE), a representative Ox-PE, was prepared using a selective oxidation method. The difference in toxicity between LDPE-MPs and Ox-LDPE-MPs were evaluated in C57BL/6 mice and Caco-2 cells. The proton nuclear magnetic resonance (1H NMR) and Fourier transform infrared (FTIR) spectroscopy analyses revealed that some hydrocarbon-containing groups were transformed into carboxyl and ketone groups during selective oxidation. In vivo experiment results showed that LDPE-MPs and Ox-LDPE-MPs exists in the intestinal (duodenum and colon) of mice, and Ox-LDPE-MPs caused more severe intestinal histological changes, oxidative stress, and inflammatory response. The gut microbiota data showed that the relative abundance of Lactobacillus decreased significantly in the LDPE-MP- and Ox-LDPE-MP-exposed groups (P < 0.05). The predicted Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathway suggested that exposure to LDPE-MPs or Ox-LDPE-MPs inhibited glycan biosynthesis and metabolism in the flora (P < 0.05). In vitro experiment results showed that selective oxidation to LDPE promoted its uptake by cells and aggravated adverse effects on cells, including reduced cell viability, damaged cell membrane, oxidative stress, and mitochondrial depolarization. The major mechanism of the increased toxicity of Ox-LDPE-MPs may be its easier accumulation and the ionic effect of oxygen-containing functional groups. Overall, these findings provide insights on the differences in toxicity between LDPE-MPs and Ox-LDPE-MPs. They also provide new perspectives for understanding the biohazards of MPs, which are necessary to accurately assess the potential environmental and health risks of these plastic pollutants.


Quantitative ultrasound assessment of the effect of parity on bone mineral density in females.
The effect of pregnancy and breastfeeding on a female's bone mineral density (BMD) is controversial. This prospective study aims to investigate the effect of parity on BMD among pre-menopausal multiparous females using quantitative ultrasound as a screening method and females with no pregnancies (nulliparous) as a control group. A portable ultrasound-based bone densitometer (DMS PEGASUS SMART, Mauguio, France) was used to indirectly assess the BMD in 51 multiparous (29-45 years) and 51 nulliparous Arabic females (18-35 years) by quantifying the broadband ultrasound attenuation (BUA) from their right calcaneus bone. BUA > 70 db/mhz = normal, BUA 65-69.9 db/mhz = below average, BUA 55-64.9 db/mhz = osteopenia and BUA < 55 db/mhz = osteoporosis. There was a significant difference in mean BUA between multiparous and nulliparous females (74.1 db/mhz vs. 69.3 db/mhz, p = 0.006). The prevalence of normal BMD was significantly higher in the nulliparous group than in the multiparous group (70.6% vs. 47.1%, p = 0.02). Osteoporosis was found in the multiparous group only (3/51). Among the multiparous females who breastfed (43/51), a total of 51.2% (22/43) had normal BMD, 25.6% (11/43) had BMD below average, 18.6% (8/43) had osteopenia and 4.7% (2/43) had osteoporosis. No significant differences in mean BUA (p = 0.2) were found between the group of females who breastfed for one year (13/43; BUA: 70.5 ± 9.4), the group of females who breastfed for 6-11 months (8/43; BUA: 70.6 ± 10.0) and those who breastfed for less than six months (22/43; BUA: 71.6 ± 9.4). A binary logistic regression model built for predicting BMD normality showed significance for the variable parity (p = 0.03), while the effect of the possible confounding variables BMI and age on BMD normality was found to be non- significant (p = 0.1 and p = 0.6, respectively). Parity affects the BMD, as assessed by a portable ultrasound-based bone densitometer, of young and middle-aged females as compared to the BMD of nulliparous females.


Conformational changes in concanavalin A associated with demetallization and alpha-methylmannose binding studied by Fourier transform infrared spectroscopy.
Infrared spectra of concanavalin A have been obtained both in the absence and in the presence of the metal ions, Mn2+ and Ca2+, and the saccharide, alpha-methylmannose. Second derivative calculations have been used to determine the frequencies of the different amide I and II components. In the demetallized protein dissolved in H2O buffer, absorptions in the amide I, II and III regions at 1695 and 1634, 1532 and 1237 cm-1, respectively, are assigned to beta-structure, while absorptions at 1563 and both 1318 and 1343 cm-1 are assigned to turns and bends. After deuterium exchange, the residual amide II maximum in the difference spectrum shifts from 1538 to 1563 cm-1, indicating that exchange is faster in the beta-structure than in the turns. In the presence of Mn2+ and Ca2+, the amide II band component at 1532 cm-1 shifts 4-6 cm-1 to higher wavenumbers, and the amide I band component at 1634 shifts 1 cm-1 in the same direction, both in H2O and 2H2O buffers, suggesting changes in the hydrogen-bonding network of a large portion of the protein, particularly in the beta-sheet regions. The addition of alpha-methylmannose increases the magnitude of exchange from 55% to above 90%. Comparison with existing X-ray crystallographic data has been made, and the usefulness of FT-IR to complement this technique is discussed.


CXCL10 encoding synNotch T cells enhance anti-tumor immune responses without systemic side effect.
Modifying T cells to attack tumors using engineered chimeric receptors display powerful new therapeutic capabilities. Unfortunately, the effectiveness of therapeutic T cells is limited due to the inherent T cell responses: certain facets of endogenous response programs may be toxic, and the ability to overcome the immunosuppression in TME is deficient. Here we developed a Notch receptor based synNotch T cell platform that is able to response to target tumor cells and selectively lead to CXCL10 production. Further study showed that the administration of synNotch T cells significantly inhibited the tumor growth in a humanized murine model, accompanied by the increased infiltration of CD3+T cells and elevated level of CXCL10 and IFN-γ in the tumor site. A slightly increased level of CXCL10 and limited IFN-γ were found in the serum in mice received synNotch T cells, suggesting a high security of this treatment. Finally, we demonstrated that CXCL10 is sufficient and indispensable for the synNotch T cells induced anti-tumor effect. This study provided theoretical and experimental bases for the clinical implication of CXCL10 encoding synNotch T cells.


Longitudinal Invariance and Construct Validity of the Chinese Version of the Mini-Mental State Examination Across 10 Years in the Elderly Population.
Background and Purpose: In this study, we investigate the longitudinal measurement invariance of the Chinese version of the mini-mental state examination (CMMSE). Methods: The factor structure and longitudinal equivalence of the CMMSE were examined by confirmatory factor analyses. Four CMMSE measurements of 13,132 participants from the China Longitudinal Health and Longevity Study between 2008 and 2018 were included. The nested model of longitudinal invariance proves the existence of strict longitudinal invariance. Results: It showed that the factor structure, factor loadings, intercept error variance, and latent factor means of the CMMSE were invariant across four measurements. Conclusion: These findings indicate that the changes in CMMSE scores can be attributed to real structural change, indicating that the CMMSE is a reliable measurement tool for the study of cognitive aging.


Testosterone Administration Moderates Effect of Social Environment on Trust in Women Depending on Second-to-Fourth Digit Ratio.
Animal research has established that effects of hormones on social behaviour depend on characteristics of both individual and environment. Insight from research on humans into this interdependence is limited, though. Specifically, hardly any prior testosterone experiments in humans scrutinized the interdependency of testosterone with the social environment. Nonetheless, recent testosterone administration studies in humans repeatedly show that a proxy for individuals' prenatal testosterone-to-estradiol ratio, second-to-fourth digit-ratio (2D:4D ratio), influences effects of testosterone administration on human social behaviour. Here, we systematically vary the characteristics of the social environment and show that, depending on prenatal sex hormone priming, testosterone administration in women moderates the effect of the social environment on trust. We use the economic trust game and compare one-shot games modelling trust problems in relations between strangers with repeated games modelling trust problems in ongoing relations between partners. As expected, subjects are more trustful in repeated than in one-shot games. In subjects prenatally relatively highly primed by testosterone, however, this effect disappears after testosterone administration. We argue that impairments in cognitive empathy may reduce the repeated game effect on trust after testosterone administration in subjects with relatively high prenatal testosterone exposure and propose a neurobiological explanation for this effect.


Quantitation of proteins by dot-immunobinding assay. A comparison of visualization methods using eukaryotic initiation factor 2 and a monospecific antibody.
Various visualization methods were compared for quantitation of proteins by the dot-immunobinding assay. Comparisons were carried out using a multi-subunit protein, eukaryotic initiation factor 2, and monospecific antibodies directed against two of the factor's subunits. The protein was spotted onto nitrocellulose and the membranes were incubated with primary antibody. The antigen-antibody complex was visualized by one of six methods using either alkaline phosphatase-, horseradish peroxidase-, or glucose oxidase-conjugated IgG, or colloidal gold-labelled IgG, colloidal gold-labelled IgG with silver enhancement, or 125I-labelled protein A. The amount of secondary antibody bound was quantitated by densitometric scanning of the nitrocellulose membrane after staining or autoradiography. The sensitivity of each of the methods was similar; each of the visualization methods could detect less than 1 ng of protein by the dot-immunobinding assay. Curves of protein concentration vs. densitometric absorbance were found to fit a parabolic relationship (r2 = 0.99) over a wide range of concentrations.


Schizophrenia genes: on the matter of their convergence.
Schizophrenia is a common mental disorder, affecting 0.5-1% of the population. The mode of inheritance is complex and non-Mendelian with a high heritability of ca. 65-80%. Given this complexity, until most recently it was difficult to identify disease genes. But fortunately this has changed. Due to new technologies the last few years have brought highest interest in human genetics of complex diseases. The knowledge resulting from the availability of the complete sequence of the human genome, the systematic identification of single nucleotide polymorphisms (SNPs) throughout the genome, and the development of parallel genotyping technology (microarrays) established the conditions that brought about the current successful time in our ability to probe the genome for identifying disease genes. All these studies showed up new avenues for the biology of common complex diseases and yielded a multitude of genes showing strong association with complex diseases.


Real-world comparison of pembrolizumab and nivolumab in advanced hepatocellular carcinoma.
Nivolumab and pembrolizumab have not been directly compared in clinical trials, and the aim of this study is to investigate the efficacy and safety of nivolumab versus pembrolizumab in patients with advanced hepatocellular carcinoma (HCC) in real-world practice. We retrospectively reviewed patients with HCC who received intravenous nivolumab or pembrolizumab alone as second-line and later therapy. The objective response was determined according to the Response Evaluation Criteria in Solid Tumors criteria version 1.1. Adverse events (AEs) were graded based on the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0. The Kaplan-Meier method was used to analyze progression-free survival (PFS) and overall survival (OS). Prognostic values were estimated using hazard ratios with 95% confidence intervals (CIs). In total, 120 patients were enrolled, including 95 who received nivolumab and 25 who received pembrolizumab. All patients were staged as Barcelona Clinic Liver Cancer stage C, and 29 patients were classified as Child-Pugh classification B (7). The response rate of the pembrolizumab and nivolumab groups were 8.0% and 7.4%, respectively. There was no significant difference in the median PFS between the pembrolizumab and nivolumab groups (2.7 months versus 2.9 months). The median OS in the nivolumab group was longer than that in the pembrolizumab group (10.8 months versus 8.1 months); however, the difference was not statistically significant. The effects of pembrolizumab and nivolumab on the median PFS and OS were consistent across the subgroups based on baseline characteristics. The severity of all AEs was grades 1-2 without treatment interruption or dose adjustment; there was no statistically significant difference in the incidence of treatment-related AEs between these two groups. Additionally, the percentage of patients receiving subsequent therapy was consistent between the two groups. The efficacy and safety of pembrolizumab and nivolumab were comparable in the management of patients with pretreated HCC in real-world practice.


Common nerve blocks in chronic pain management.
Anesthesiologists have become increasingly involved with the management of chronic pain patients in the operating room, on the surgical floor, and in the outpatient pain facility setting (often interdisciplinary). Based upon the authors' practice of regional anesthesia, the most specific contribution to chronic pain management arguably remains the practice of diagnostic, prognostic, and therapeutic injections of the neuraxis, peripheral nerves, and the autonomic nervous system.


Field-measured uptake rates of PCDDs/Fs and dl-PCBs using PUF-disk passive air samplers in Gyeonggi-do, South Korea.
The collection of 2,3,7,8-substituted polychlorinated dibenzo-ρ-dioxins and dibenzo furans (PCDDs/Fs) and dioxin-like polychlorinated biphenyls (dl-PCBs) using a polyurethane form (PUF)-disk passive air sampler (PAS) was investigated in urban-residential and industrial areas. This was performed to assess the feasibility of using this method as an alternative to an active air sampler (AAS). The PUF-disk PAS was exposed to ambient air over a period of 37-370 and 57-173 days in urban and industrial areas, respectively, together with AASs. The sum of total toxic equivalent quantity (TEQ) ΣPCDDs/Fs and Σdl-PCB was typically high in the industrial area, with values within the range 0.171-0.635 pg-TEQ/m(3), and 0.037-0.300 pg-TEQ/m(3) in the urban-residential area. To derive the time-weighted average (TWA) concentration from the PAS data accurately, it was estimated that the PAS deployed for less than 80 days was adequate to maintain linear accumulation conditions. PCDDs/Fs are mainly particle bound and showed low average uptake rates of 1.4m(3)d(-1), while dl-PCBs were slightly higher with 2.0m(3)d(-1) because of its high vapor pressure. Most of the congener concentrations measured using the PAS and AAS were within a factor of two, indicating that PASs can be used to monitor spatial and temporal variations in the concentrations of persistent organic pollutants (POPs) in the atmosphere.


An uncertain life: demography in random environments.
This paper concisely reviews the demography of populations with random vital rates, highlights examples and techniques which yield insight into population dynamics, summarizes the state of significant applications of the theory, and points to open problems. The central picture in this theory is of a time-varying but statistically stationary equilibrium for population, sharply distinct from the notions of classical demography. The deepest biological insights from the theory reveal the temporal structure of life histories to be a rich arena for natural selection.


Pretransplant Tacrolimus Dose Requirements Predict Early Posttransplant Dose Requirements in Blood Group AB0-Incompatible Kidney Transplant Recipients.
The aim of this study was to investigate whether pretransplant tacrolimus (Tac) dose requirements of patients scheduled to undergo living donor kidney transplantation correlate with posttransplantation dose requirements. The predictive value of Tac dose requirements (defined as the ratio of the Tac predose concentration, C0, divided by the total daily Tac dose, D) pretransplantation on this same parameter posttransplantation was assessed retrospectively in a cohort of 57 AB0-incompatible kidney transplant recipients. These patients started immunosuppressive therapy 14 days before transplant surgery. All patients were using a stable dose of glucocorticoids and were at steady-state Tac exposure before transplantation. Tac dose requirements immediately before transplantation (C0/Dbefore) explained 63% of the Tac dose requirements on day 3 after transplantation: r = 0.633 [F (1, 44) = 75.97, P < 0.01]. No other clinical and demographic variables predicted Tac dose requirements early after transplantation. Steady-state Tac dose requirement before transplantation largely predicted posttransplantation Tac dose requirements in AB0-incompatible kidney transplant recipients. The importance of this finding is that the posttransplantation Tac dose can be individualized based on a patient's pretransplantation Tac concentration/dose ratio. Pretransplant Tac phenotyping therefore has the potential to improve transplantation outcomes.


A systematic literature review of criteria and models for casualty distribution in trauma related mass casualty incidents.
Mass casualty incidents impose a large burden on the emergency medical systems, hospitals and community infrastructures. The pre-hospital and hospital capacities are usually bear the burden of casualties large numbers. One of the challenging issues in mass casualty incidents is the distribution of casualties among the suitable health care facilities. To review models and criteria affecting the distribution of casualties during the trauma-related mass causality incidents. A systematic literature search in the scientific databases which included: PubMed, Scopus and Web of Science was conducted. Relevant literature which was published before August 2017 was searched. Neither the publication date nor language limitations were considered in the literature search. All the trauma-related mass casualty incidents are included in this study. Two independent reviewers conducted the data extraction and quality assessment of the documents was considered using a checklist developed by the researchers. Literature search yielded 4540 documents of which 493 were duplicated and removed. After reviewing the titles and abstracts of the remaining documents (4047), only 73 documents were considered relevant. Finally, the inclusion and exclusion criteria were applied and only 30 documents were considered for data extraction and quality assessment. The study found 491 criteria to be affecting the distribution of casualties following trauma-related mass casualty incidents. These are categorized as pre-hospital (triage, treatment and transport); hospital (space, staff, stuff, system / structure); incidents' characteristics and others. The criteria which were extracted from the models are termed as "model extracted" while the other labeled as "author suggested". To the best of our knowledge, this is the first systematic literature review on criteria affecting distribution of casualties following trauma-related mass casualty incidents based on the pre-hospital and hospital capacities. This review was registered in international prospective register of systematic reviews (PROSPERO) with registration number CRD42016049115.


Mammographic density: Comparison of visual assessment with fully automatic calculation on a multivendor dataset.
To compare breast density (BD) assessment provided by an automated BD evaluator (ABDE) with that provided by a panel of experienced breast radiologists, on a multivendor dataset. Twenty-one radiologists assessed 613 screening/diagnostic digital mammograms from nine centers and six different vendors, using the BI-RADS a, b, c, and d density classification. The same mammograms were also evaluated by an ABDE providing the ratio between fibroglandular and total breast area on a continuous scale and, automatically, the BI-RADS score. A panel majority report (PMR) was used as reference standard. Agreement (κ) and accuracy (proportion of cases correctly classified) were calculated for binary (BI-RADS a-b versus c-d) and 4-class classification. While the agreement of individual radiologists with the PMR ranged from κ = 0.483 to κ = 0.885, the ABDE correctly classified 563/613 mammograms (92 %). A substantial agreement for binary classification was found for individual reader pairs (κ = 0.620, standard deviation [SD] = 0.140), individual versus PMR (κ = 0.736, SD = 0.117), and individual versus ABDE (κ = 0.674, SD = 0.095). Agreement between ABDE and PMR was almost perfect (κ = 0.831). The ABDE showed an almost perfect agreement with a 21-radiologist panel in binary BD classification on a multivendor dataset, earning a chance as a reproducible alternative to visual evaluation. Individual BD assessment differs from PMR with κ as low as 0.483. An ABDE correctly classified 92 % of mammograms with almost perfect agreement (κ = 0.831). An ABDE can be a valid alternative to subjective BD assessment.


Immune-competent human skin disease models.
All skin diseases have an underlying immune component. Owing to differences in animal and human immunology, the majority of drugs fail in the preclinical or clinical testing phases. Therefore animal alternative methods that incorporate human immunology into in vitro skin disease models are required to move the field forward. This review summarizes the progress, using examples from fibrosis, autoimmune diseases, psoriasis, cancer and contact allergy. The emphasis is on co-cultures and 3D organotypic models. Our conclusion is that current models are inadequate and future developments with immune-competent skin-on-chip models based on induced pluripotent stem cells could provide a next generation of skin models for drug discovery and testing.


Met-enkephalin: rapid separation from brain extracts using high-pressure liquid chromatography, and quantitation by binding assay.
Met-enkephalin can be rapidly separated with high recovery from leu-enkephalin, beta-endorphin, and enkephalin metabolites by high-pressure liquid chromatography on a Dupont SCX column. The technique permits separation of endogenous enkephalins from brain extracts for measurement by opiate-receptor binding assay, immunoassay, or for study of the incorporation of radiolabeled amino acids into enkephalin. Using this technique, met-enkephalin was separated from striatal extracts of rats killed by focused microwave irradiation and quantitated by the opiate-receptor binding assay. The concentration of met-enkephalin in the column eluate was 1.3 micron/g tissue. This value is comparable to that obtained by radioimmunoassay without purification of the extracts.


Changes in growth performance, metabolic enzyme activities, and content of Fe, Cu, and Zn in liver and kidney of tilapia (Oreochromis niloticus) exposed to dietary Pb.
Tilapia (Oreochromis niloticus) were exposed to 0, 100, 400, and 800 microg/g concentrations of Pb in diet for 60 days, and changes in growth performance, metabolic enzyme activities, and essential trace elements (Fe, Cu, and Zn) content in liver and kidney were investigated. Daily weight gain, feed conversation ratio, and survival of tilapia were not significantly affected by dietary Pb. Alanine transaminase (ALT), aspartate transaminase (AST), and lactate dehydrogenase (LDH) activities in liver and kidney were affected by dietary Pb in a dissimilar way: Pb concentration-related decreases in ALT, AST, and LDH activities were observed in kidney, while these enzyme activities in liver were stimulated in a Pb concentration-dependent manner. It was demonstrated that the inhibitory effects of dietary Pb on alkaline phosphatase, Na, K-adenosine triphosphatase (ATPase), Ca, and Mg-ATPase activities in both liver and kidney were Pb concentration-dependent. It was also indicated that the content of Fe, Cu, and Zn in liver and kidney decreased with the increasing dietary Pb concentrations. The results suggested that long-term dietary Pb exposure could affect metabolic enzyme activities and the content of Fe, Cu, and Zn in liver and kidney, whereas growth impairment was not observed in tilapia.


Morphometric characteristics of the thoracοlumbar and lumbar vertebrae in the Greek population: a computed tomography-based study on 900 vertebrae-"Hellenic Spine Society (HSS) 2017 Award Winner".
Vertebrae morphology appears to have genetic and ethnic variations. Knowledge of the vertebra and pedicle morphology is essential for proper selection and safe application of transpedicular screws. The aim of this study is to create a morphometric database for thoracolumbar and lumbar vertebrae (T9-L5) among individuals of both sexes in the Greek population. The morphometric dimensions of T9-L5 vertebrae on computed tomography (CT) scan images were measured in 100 adults (79 males and 21 females), without spinal pathology, age from 33 to 87 years old (mean 70 ± 8.73 years). The anterior vertebral body height (AVBH), the posterior vertebral body height (PVBH), the angle formed by the upper end plate of vertebral body and the horizontal line in the sagittal plane, the inner cancellous and outer cortical pedicle height and width, the angle formed by the longitudinal trajectory of the right- and left-sided pedicles and the midline anteroposterior axis of the vertebra (pedicle axis angle (PAA)), and the postero-anterior trajectory's length of the pedicle from the entry point to the anterior cortex of the vertebra (PTLP), for the right- and left-sided pedicles, were calculated. The Mann-Whitney U tests were conducted to compare the differences in various morphometric characteristics between sexes. The collected data were statistically analyzed using the SAS/STAT software 3.1.3 and SPSS version 22. The statistical significance was set at the level of p < 0.05. The intra- and inter-observer reliability of the measured parameters was also calculated. The L5 vertebra had the maximum AVBH with a mean of 28.47 mm (SD ± 2.55 mm) in males and 26.48 mm (SD ± 1.61 mm) in females. The maximum PVBH in males was at L1 vertebra with a mean of 27.77 mm (SD ± 1.64 mm) and in females at L2 vertebral with a mean of 27.11 mm (SD ± 1.27 mm). Regarding the left pedicle dimensions, the maximum inner cancellous and outer cortical pedicle height was at T11 with a mean of 12.86 mm (SD ± 1.26 mm) and 18.82 mm (SD ± 1.37 mm) in males and 10.24 mm (SD ± 1.88 mm) and 16.19 mm (SD ± 3.27 mm) in females, respectively. The maximum inner cancellous and outer cortical pedicle width was at L5 with a mean of 11.57 mm (SD ± 1.97 mm) and 17.08 mm (SD ± 1.97 mm) in males and 10.24 mm (SD ± 1.88 mm) and 16.27 mm (SD ± 3.27 mm) in females, respectively. The largest PAA was found at the L5 with a mean angle of 26.23° (SD ± 2.65°) in males and 23.63° (SD ± 4.59°) in females, respectively. The maximum PTLP was found at the level of L4 with a mean of 55.31 mm (SD ± 4.52 mm) in males and 48.7 mm (SD ± 4.17 mm) in females, respectively. Regarding the right pedicle dimensions, the maximum inner cancellous and outer cortical pedicle height was found at T12 with a mean of 13.03 mm (SD ± 2.01 mm) and 18.01 mm (SD ± 1.56 mm) in males and 10.24 mm (SD ± 1.23 mm) and 16.14 mm (SD ± 1.23 mm) in females, respectively. The maximum inner cancellous and outer cortical pedicle width was at L5 with a mean of 11.3 mm (SD ± 2.86 mm) and 16.34 mm (SD ± 2.98 mm) in males and 12 mm (SD ± 3.18 mm) and 15.69 mm (SD ± 2.59 mm) in females, respectively. The greater PAA was at the L5 vertebral with a mean of 25.7° (SD ± 5.19°) in males and 25.56° (SD ± 5.31°) in females, respectively. The maximum PTLP was at the level of L3 with a mean of 54.86 mm (SD ± 3.18 mm) in males and 49.01 mm (SD ± 2.97 mm) in females, respectively. At all vertebrae, the only statistically significant difference (p < 0.0001) between the two sexes was the mean PTLP of the right and the left pedicle. The L5 vertebra was found to have the largest AVBH, PAA, and pedicle width in male and female populations. This study provides a database of morphometric characteristics on thoracolumbar and lumbar vertebrae from T9 to L5 in the Greek population. This database may prove to be of great significance for forthcoming comparative studies. It can also serve as a basis in order to detect pathological changes in the spine and furthermore to plan operative interventions. It was found that the dimensions of thoracolumbar and lumbar vertebrae in the Greek population are sex-dependent. In the current study, vertebra and pedicle dimensions seem to have some similarities compared to other Western populations. However, in the thoracolumbar region, the pedicles of T9 and T10 may hardly accommodate a 4.00-mm pedicle screw given the narrow inner cancellous pedicle width. Importantly, the vertebra and pedicle dimensions measured in the current study can be used to guide the selection of transpedicular screws in the Greek population and to guide further research.


Measurement of drug facilitated sexual assault agents in simulated sweat by ion mobility spectrometry.
Ion mobility spectrometry has found widespread use for the detection of explosives and illicit drugs. The technique offers rapid results with high sensitivity and little sample preparation. As such, it is well suited for field deployed screening settings. Here the response of ion mobility spectrometers for three drug-facilitated sexual assault (DFSA) agents - flunitrazepam, ketamine, and MDMA - and related metabolites has been studied in the presence of a simulated sweat. While all three DFSA agents present certain challenges for qualitative identification, IMS can provide useful information to guide the early treatment and investigation of sexual assault cases. Used as a presumptive test, the identification of DFSA agents would later require confirmatory analysis by other techniques.


Dual role as a protective factor for burnout-related depersonalization in oncologists.
This study compared self-reported burnout between dual-role oncologists (oncologists who also do psychosocial work) and single-role oncologists, to explore if dual role is protective against or a risk factor for burnout. Dual-role oncologists from across China (n = 131) were consecutively recruited via the Chinese Psychosocial Oncology Society and asked to identify single-role oncologist peers (n = 168) working in the same institution. Participants completed an anonymous online questionnaire, which included measures of demographic and work characteristics, Maslach Burnout Inventory-Human Services Survey, the Short Version Effort-Reward Inventory, the Job Demands-Resources (JD-R) Scales, and Work and Meaning Inventory. Fully adjusted multivariate analyses compared burnout scores for the 2 groups. Group analysis revealed single-role participants' scores indicated significantly poorer performance than dual-role participants for depersonalization (DP), work-family conflict (JD-R demands scale), and decision authority (JD-R scale). Single-role participants showed an increased risk of DP. Higher effort-reward imbalance ratio predicted greater DP in single-, dual-role and pooled participants, and emotional exhaustion (EE) in pooled- and dual-role participants. Overcommitment was independently associated with EE in all 3 groupings, with JD-R scores among pooled- and dual-role groups, while higher decision authority scores were associated with decreased EE. Work and Meaning Inventory was associated with a decreased risk of DP among pooled and dual-role participants. Differences in burnout-related DP scores between dual- and single-role oncologists are consistent with a protective effect from a psychosocial orientation in oncologists.


Exogenous gonadotropin administration affects the glycocalyx of rat endometrial epithelial cells during the period of implantation.
Exogenous gonadotropins which cause superovulation are known to effect endometrial morphology, including the glycocalyx of surface epithelial cells. Certain of the carbohydrates in the glycocalyx of surface epithelial cells may be involved in the attachment and implantation of the blastocyst. The effect of exogenous gonadotropins on specific carbohydrates in the glycocalyx of the rat endometrium around the time of implantation was investigated. Lectin-avidin-biotin-ferritin cytochemistry was used to ascertain which carbohydrates were affected. The lectins soybean agglutinin, fucose binding protein and wheat germ agglutinin were used. Statistically significantly less lectin was associated with the apical membrane of surface epithelial cells of animals following hyperstimulation than in noninjected pregnant animals. The reduction in the carbohydrates contributes to a reduced receptivity of the endometrium for the blastocyst.


Aspects of gap junction structure and assembly.
The development of ideas about gap junction structure is summarized, including some recent results obtained by use of atomic force microscopy. Particular attention is paid to novel aspects of the biosynthesis and assembly of connexons and to the formation of new junctions.


Continued aortic aneurysmal expansion after thoracic endovascular stent-grafting.
We report the successful open repair of a thoracoabdominal aneurysm that had expanded after previous endovascular stenting. Aortic valve-sparing root replacement was performed as an initial step because the patient had significant aortic valve regurgitation caused by root enlargement. Continued aneurysmal dilatation after stenting of the thoracic aorta can lead to repair failure and therefore underscores the need for careful follow-up of patients after endografting.


Freeze-substitution of Drosophila heads for subsequent [3H]2-deoxyglucose autoradiography.
High resolution of [3H]2-deoxyglucose labelling was obtained in autoradiographs of Drosophila brains after freeze-substitution in anhydrous acetone at -76 degrees C. This method was applied to preparations which received visual, olfactory and mechanosensory stimulation. The autoradiographs were compared to those obtained after freeze-drying. Freeze-substitution, which has proved to be technically simple, rapid and inexpensive, yields a good quality of tissue preservation and hence is recommended for tissue dehydration prior to autoradiography.


Paternity cases.
Through analysis of 350 expertises in suits, where the man was accused of paternity, was found that these examinees often lived in a sterile marriage. When examined they often try to influence negatively the result of spermiologic examination. Sterility was ascertained here in only about 10% of cases. In the material consisting of 98 expertises in suits for denial of paternity it was found that about one half of these men were either divorced or in the course of divorce proceedings and about one third of them stated the infidelity of the wife. In more than one third of these cases sterility was proved. The court expert must often express his opinion as to the fertility of the man two or more years previously. His conclusion is especially difficult, where the spermiologic findings repeatedly vary within the limits of severe oligozoospermia with less than 5 million spermatozoids per 1 ml and where the motility is poor.


Inhibition of transport system b0,+ in blastocysts by inorganic and organic cations yields insight into the structure of its amino acid receptor site.
The most conspicuous, Na(+)-independent amino acid transport process in preimplantation mouse blastocysts was provisionally designated system b0,+ because it accepts some cationic and zwitterionic amino acids about equally well as substrates. Although system b0,+ is not Na(+)-stimulated, it has not been determined if it is inhibited by Na+, or if its activity is affected by most other ions. Therefore, we measured uptake of amino acids by blastocysts in isotonic solutions of different ionic and nonionic osmolites. Na(+)-independent L-leucine uptake was unaffected by the ion concentration, but L-lysine transport was several-fold faster in isotonic solutions of non-electrolytes than in similar solutions of inorganic and organic salts or zwitterions. The Km value for 'Na(+)-independent' L-lysine transport was about 10-fold higher in isotonic salt solutions than in solutions of nonionic osmolites, whereas the Km value for L-leucine transport was about the same in either type of solution. Therefore, inorganic and organic cations and the cationic portions of zwitterions appear to compete with cationic but not zwitterionic amino acids for system b0,+ receptor sites. The cation, harmaline, was a particularly strong competitive inhibitor of 'Na(+)-independent' L-lysine uptake by system b0,+, even in isotonic salt solutions, whereas it inhibited L-leucine uptake noncompetitively. Moreover, harmaline appeared to compete with inorganic cations for the lysine receptor sites of system b0,+. Harmaline also has been found by other investigators to competitively inhibit L-lysine uptake by the Na(+)-independent system asc1 in horse erythrocytes, whereas it noncompetitively inhibits alanine uptake by the same system. Similarly, harmaline noncompetitively inhibits L-alanine uptake by the Na(+)-dependent system ASC in human erythrocytes, but it appears to compete for binding with L-alanine's cosubstrate, Na+. In addition, others have found that the positively-charged side chains of cationic amino acids seem to take the place of Na+ needed near side chains in order for zwitterionic amino acids to be transported by systems ASC and y+. We conclude that system b0,+ may be similar to systems asc1, ASC and y+, and that each of these systems may be a variant of the same ancestral transport process. We speculate that since it appears to accept a broader scope of substrates and to interact with a wider variety of cations than do systems asc1, ASC or y+, system b0,+ may more closely resemble the proposed ancestral transport process than any of the other contemporary systems.


Fast degradation of diclofenac by catalytic hydrodechlorination.
Aqueous-phase catalytic hydrodechlorination (HDC) has been scarcely explored in the literature for the removal of chlorinated micropollutants. The aim of this work is to prove the feasibility of this technology for the fast and environmentally-friendly degradation of such kind of compounds. Diclofenac (DCF), a highly consumed anti-inflammatory drug, has been selected as the target pollutant given its toxicity and low biodegradability. The commercial Pd/Al2O3 (1% wt.) catalyst has been used due to its prominent role on this field. Complete degradation of DCF was achieved in a short reaction time (20 min) under ambient conditions (25 °C, 1 atm) at [DCF]0 = 68 μM; [Pd/Al2O3]0 = 0.5 g L-1 and H2 flow rate of 50 N mL min-1. Remarkably, the chlorinated intermediate (2-(2-chloroanilino)-phenylacetate (Cl-APA)) generated along reaction was completely removed at the same time, being the chlorine-free compound 2-anilinophenylacetate (APA) the only final product. A reaction scheme based on this consecutive pathway and a pseudo-first-order kinetic model have been proposed. An apparent activation energy of 43 kJ mol-1 was obtained, a comparable value to those previously reported for conventional organochlorinated pollutants. Remarkably, the catalyst exhibited a reasonable stability upon three successive uses, achieving the complete degradation of the drug and obtaining APA as the final product in 30 min. The evolution of ecotoxicity was intimately related to the disappearance of the chlorinated organic compounds and thus, the final HDC effluents were non-toxic. The versatility of the system was finally demonstrated in different environmentally-relevant matrices (wastewater treatment plant effluent and surface water).


Prevalence of diabetes type 2 in older adults: Findings from a large population-based survey in Tehran, Iran (Urban HEART-2).
Diabetes is a common problem in older adults, as they increasingly comprise a larger proportion of patients newly diagnosed with diabetes. The evidence on the prevalence and distribution of type 2 diabetes (DT2) and its related factors among older adults in Iran is sparse. The aim of the present study was to determine the prevalence of DT2 among Iranian older adults aged ≥60years. The study was part of a comprehensive survey (Urban HEART-2) which was a large population-based cross-sectional study. A multistage cluster random sampling method was used to select the participants in Tehran in 2011. All the participants were interviewed by trained personnel using a standard questionnaire on diabetes as well as a socio-demographic checklist. Logistic regression and chi-square were used to investigate the association between diabetes and the demographic characteristics. A total of 15069 older adults were included in this analysis. The mean age of the participants was 68.93±7.27years (SE: 0.059) and the mean of BMI was 26.21±4.40kg/m2 (SE: 0.036). Prevalence of DT2 was 14.4% among Iranian older adults. Factors such as age, being female, high BMI, and education were significantly associated with DT2. Given the high prevalence of diabetes among older people, more population based research is needed to quantify the ramifications of diabetes, and to monitor the effects of prevention and health system strengthening strategies on the prevalence, treatment, and control of DT2.


Top-down versus bottom-up attention differentially modulate frontal-parietal connectivity.
The moment-to-moment focus of our mind's eye results from a complex interplay of voluntary and involuntary influences on attention. Previous neuroimaging studies suggest that the brain networks of voluntary versus involuntary attention can be segregated into a frontal-versus-parietal or a dorsal-versus-ventral partition-although recent work suggests that the dorsal network may be involved in both bottom-up and top-down attention. Research with nonhuman primates has provided evidence that a key distinction between top-down and bottom-up attention may be the direction of connectivity between frontal and parietal areas. Whereas typical fMRI connectivity analyses cannot disambiguate the direction of connections, dynamic causal modeling (DCM) can model directionality. Using DCM, we provide new evidence that directed connections within the dorsal attention network are differentially modulated for voluntary versus involuntary attention. These results suggest that the intraparietal sulcus exerts a baseline inhibitory effect on the frontal eye fields that is strengthened during exogenous orienting and attenuated during endogenous orienting. Furthermore, the attenuation from endogenous attention occurs even with salient peripheral cues when those cues are known to be counter predictive. Thus, directed connectivity between frontal and parietal regions of the dorsal attention network is highly influenced by the type of attention that is engaged.


Dual-task changes in gait and brain activity measured in a healthy young adult population.
Dual Task (DT) walking in everyday life is the norm rather than the exception. Complex cognitive-motor strategies are employed during DT and it is necessary to coordinate and regulate neural resources to ensure adequate performance. However, the underlying neurophysiology involved is not fully understood. Therefore, the aim of this study was to examine the neurophysiology and gait kinematics during DT gait. Our main research question was whether gait kinematics changed during DT walking for healthy young adults and whether this is reflected in brain activity. Ten healthy young adults walked on a treadmill, performed a Flanker test while standing and performed the Flanker test while walking on a treadmill. Electroencephalography (EEG), spatial temporal, and kinematic data was recorded and analyzed. Average alpha and beta activities were modulated during DT walking compared to single task (ST) walking while ERPs during the Flanker test showed larger P300 amplitudes and longer latencies for DT compared to standing. Cadence reduced and cadence variability increased during DT compared to ST whilst kinematic results showed that hip and knee flexions decreased, and the center of mass moved slightly back in the sagittal plane. It was found that healthy young adults employed a cognitive-motor strategy that included directing more neural resources to the cognitive task while adopting a more upright posture during DT walking.


Chemical Comparison of Ophiopogonis radix and Liriopes radix Based on Quantitative Analysis of Multiple Components by HPLC Coupled with Electrospray Ionization Tandem Triple Quadrupole Mass Spectrometry.
Ophiopogonis radix and Liriopes radix are well known for the treatment of dry coughs and phthisis. Liriopes radix is occasionally used as a substitute for Ophiopogonis radix in various prescriptions due to the extremely similar pharmacological activities and clinical efficacies, but they are regarded as two different remedies in the Chinese Pharmacopoeia. Accordingly, the establishment of a reliable analytical approach for the discrimination and quality evaluation of Ophiopogonis and Liriopes is required. To establish a simple, accurate, and reliable method that can simultaneously determine multiple components in Ophiopogonis radix and Liriopes radix. To comprehensively compare the chemical compositions of the two herbs and find markers for discrimination and quality assessments. An HPLC-ESI-triple quadrupole (QQQ)-MS/MS method was developed for simultaneous characterization and quantification of chemical components in the two herbs. The results were further analyzed by PLS discriminant analysis to provide more information about the chemical differences, as well as to evaluate the quality of each sample. A total of 23 compounds have been characterized and quantified in 31 batches of herbs from different geographical regions, among which liriopesides B, sprengerinin A, ophiopogonin B, and ophiopogonanone E contribute mostly. The contents of homoisoflavonoids were much higher in Ophiopogonis radix than in Liriopes radix, but the levels of steroidal saponins followed a contrary trend. Simultaneous determination of multiple components by HPLC-QQQ-MS/MS coupled with chemometrics analysis is an acceptable strategy to evaluate and control the quality of Ophiopogonis radix and Liriope radix. Simultaneous determination of 12 steroidal saponins and 11 homoisoflavonoids in both Ophiopogonis radix and Liriope radix by using HPLC-QQQ-MS/MS in positive ion mode, as well as the quality control study.


Prevalence of temporomandibular disorders (TMD) in obesity patients: A systematic review and meta-analysis.
Obesity is a growing epidemic in the world. It increases the risk for severe health conditions, including diabetes, heart disease and stroke. Recent research has found that obesity is associated with an increased risk for temporomandibular disorders (TMDs). The purpose of this literature review with meta-analysis is to analyse the possible association between obesity and temporomandibular disorders. Pubmed, Web of Science and Lilacs were systematically searched until 01/03/2000. Articles dealing with TMD and obesity were selected, and numbers that might be useful in the meta-analysis were extracted. Fifty articles were chosen after using all three search engines. Thirty-five articles were considered during the initial screening step. Four papers were chosen for title and abstract screening based on the PECO model. A manual search of bibliographies and the Cochrane database was also carried out, but no publications that matched the inclusion criteria were located. The articles and meta-analysis did not show a clear association between obesity and temporomandibular disorders. There is no evidence regarding the reliability of either method. Both have superimposable results.


Perianal fistulas in Crohn's disease are predominantly colonized by skin flora: implications for antibiotic treatment?
In this study we aimed to determine the microorganisms found in perianal fistulas in Crohn's disease and whether treatment with ciprofloxacin affects these microorganisms. Thirteen patients (males/females, 7/6; median age, 34 years; range, 18-61 years) with fistulas were treated with infliximab, 5 mg/kg intravenously, at weeks 6, 8, and 12 and randomized to double-blind treatment with ciprofloxacin, 500 mg bd (n = 6), or placebo (n = 7) for 12 weeks. Samples were taken at baseline and at weeks 6 and 18. In the ciprofloxacin group 10 different genera of microorganisms were identified, while 13 genera could be identified in the placebo group. Gram-negative enteric floras were present in a small minority. The genera found in patients with perianal fistulas were predominantly gram-positive microorganisms. Therefore, antimicrobial treatment should be directed toward these microorganisms.


Necrotizing enterocolitis after antipsychotic treatment involving clozapine and review of severe digestive complications -- a case report.
A case of necrotizing enterocolitis in a 19-year old man treated for schizophrenic disorder, induced by a drug association involving clozapine and requiring surgical treatment, is presented. To our knowledge only few reports have described the occurrence of this complication with atypical antipsychotics. Evidence for linking this complication to clozapine was reinforced by the absence of any viral or bacterial infection. The authors present a review of similar cases, stress the potential hazards induced by such drug combinations and discuss supposed mechanisms of this enterocolitis.


Identification of novel blood biomarkers of treatment response in cystic fibrosis pulmonary exacerbations by label-free quantitative proteomics.
Pulmonary exacerbations (PEx) are clinically impactful events for individuals with CF. Unfortunately, many CF individuals with PEx fail to regain their baseline lung function despite treatment. The objective of this study was to use unbiased proteomic technology to identify novel blood protein biomarkers that change following intravenous (IV) antibiotic treatment and to explore if changes correlate with clinical response by the end of treatment. Blood samples from 25 PEx events derived from 22 unique CF adults were collected within 24 hours of hospital admission, day 5, day 10, and IV antibiotic completion. Three-hundred and forty-six blood proteins were evaluated with label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS) quantitative proteomics and immunoassays. Forty-seven plasma proteins changed significantly following 5 days of IV antibiotic treatment (q-value ≤ 0.10). Early change in IGF2R from hospital admission to day 5 correlated with overall change in symptom score (CFRSD-CRISS) by the end of treatment (r = -0.48, p-value = 0.04). Several plasma proteins identified and quantified by label-free LC-MS/MS changed early following treatment with IV antibiotics and many of these proteins are involved in complement activation and inflammatory/immune-related pathways. Early change in IGF2R correlated with symptom response following IV antibiotic treatment and requires further validation as a predictive biomarker of symptom response.


Wood as a green and sustainable alternative for environmentally friendly & flexible electronic devices.
Electronic are usually constructed from non-renewable, non-biodegradable, and hazardous materials. Due to the frequent upgrading or discarding of electronic devices, which contributes significantly to environmental pollution, there is a high demand for electronics made from renewable and biodegradable materials with less harmful components. To this end, due to their flexibility, strong mechanical, and optical properties, wood-based electronics have become very appealing as substrates especially for flexible electronics and optoelectronics. However, incorporating numerous features including high conductivity and transparency, flexibility, and mechanical robustness into an environmentally friendly electronic device remains very challenging. Herein, authors have provided the techniques used to fabricate sustainable wood based flexible electronics coupled with their chemical, mechanical, optical, thermal, thermomechanical, and surface properties for various applications. Additionally, the synthesis of a conductive ink based on lignin and the development of translucent wood as a substrate are covered. Future developments and broader applications of wood-based flexible materials are discussed in the final section of the study, with an emphasis on their potential in fields including wearable electronics, renewable energy, and biomedical devices. This research improves upon prior efforts by demonstrating new ways to simultaneously attain better mechanical and optical qualities and environmental sustainability.


Comparison of ultrasonography and surface landmarks in detecting the localization for cricothyroidotomy.
The aim of the study was to compare ultrasonography (US) and surface landmark techniques for detecting the cricothyroid membrane (CTM) to perform a cricothyroidotomy on healthy volunteers. In this prospective observational study, 5 operators and 24 models were included. The borders of the CTM were marked with an invisible pen. The operators were asked to point the CTM either with the palpation method or the US-guided fashion. The CTM was detected accurately in 80 (66.7%) attempts with palpation and 83 (69.2%) attempts with US. There was no statistically significant difference in the accuracy of detection of the CTM with palpation and US. The mean time for detecting the CTM with palpation was 8.25 ± 4.8 seconds (95% confidence interval, 7.3-9.1). The mean time for detecting CTM with US was 17 ± 9.2 seconds (95% confidence interval, 15.3-18.7). The duration for detecting the localization of the CTM was longer with US. According to the results of this study, the accuracy of US and palpation was similar in detecting the localization of the CTM. However, the duration for detecting the CTM was longer with US when compared with the palpation technique.


A transposon-like element in the deletion-prone region of the dystrophin gene.
The central portion of the dystrophin gene locus is a preferential site for deletions causing progressive muscular dystrophy of the Duchenne type (DMD). The nucleotide sequence of a deletion junction fragment from a DMD patient was determined, revealing that the proximal breakpoint of the deletion in intron 43 fell within the sequence of a transposon-like element. This segment, belonging to the THE-1 family of human transposable elements, is normally present in a complete form in intron 43 of the dystrophin gene. The deletion mutation was maternally transmitted and eliminated two-thirds of the THE-1 element. Analysis of DNA from additional DMD patients revealed a second deletion with the proximal breakpoint mapping within the same THE-1 element.


Biogenesis of Fungal Extracellular Vesicles: What Do We Know?
So far, extracellular vesicles (EVs) have been described in 15 genera of fungi. They carry molecules that contribute to the interaction of fungal cells with the host. Although the number of studies on fungal EVs has increased, the mechanisms involved in their biogenesis are still poorly understood. The current knowledge of EV biogenesis shows us that they can originate both in the cytoplasm and at the plasma membrane. In this chapter, we will focus on these two cellular sites to review what is known about the biogenesis of fungal EVs.


A computer-assisted study of macrophage behavior in HBV and nAnB related infectious chronic active hepatitis.
Activated intralobular macrophages were quantified as their lysozyme contents in liver biopsies from patients with chronic HBV and nAnB active hepatitis, and subjects with no evident liver histological damage. There were more macrophages (0.62 +/- 0.06/2,500 mu 2) with a larger area (20.36 +/- 0.87 mu 2) in HBV-related chronic active hepatitis than in controls (0.21 +/- 0.04/2,500 mu 2 and 16.01 +/- 1.48 mu 2), whereas in nAnB chronic active hepatitis their numbers were similar to that in the controls (0.22 +/- 0.03/2,500 mu 2) and their area was smaller (11.68 +/- 0.79 mu 2).


Car radiator burns: a report on 72 cases.
Seventy-two cases of car radiator burns (CRB) were treated in the Burns Unit, Hamad Medical Corporation, Doha, Qatar, over a 6-year period (1982-87). All the patients were males and most were between 20 and 40 years old. Chest wall, face and right upper limb were the commonest sites involved. Most of the patients suffered from relatively minor scalds. The scenario of the accidents as well as the topography of the burned areas were characteristic to this particular type of injury. The exceptionally high temperatures in the summer months were significantly related to the incidence of this type of burn.


Lack of a meaningful effect of anacetrapib on the pharmacokinetics and pharmacodynamics of warfarin in healthy subjects.
• Inhibition of cholesteryl ester transfer protein (CETP) is a potential new mechanism for the treatment of dyslipidaemia. Anacetrapib is a novel CETP inhibitor in development. Warfarin is a commonly prescribed anticoagulant that has a narrow therapeutic index. A drug interaction study for warfarin with a novel CETP inhibitor is expected to be helpful in defining dosing regimens. WHAT THIS STUDY: ADDS • This is the first study to show that there is no clinically meaningful pharmacokinetic interaction between anacetrapib and warfarin. The single dose pharmacokinetics and pharmacodynamics of orally administered warfarin were not meaningfully affected by multiple dose administration of anacetrapib, indicating that anacetrapib does not affect CYP 2C9 clinically. Thus, no dosage adjustment for warfarin is necessary when co-administered with anacetrapib. Anacetrapib is currently being developed for the treatment of dyslipidaemia. Since warfarin, an anticoagulant with a narrow therapeutic index, is expected to be commonly prescribed in this population, a drug interaction study was conducted. In a randomized, open-label, two-period fixed-sequence design, 12 healthy male subjects received two different treatments (treatment A followed by treatment B). In treatment A, a single oral dose of 30 mg warfarin (3 × 10 mg Coumadin(TM) ) was administered on day 1. After a washout interval, subjects began treatment B, where they were given daily 100 mg doses of anacetrapib (1 × 100 mg) beginning on day -14 and continuing through day 7, with concomitant administration of 30 mg warfarin (3 × 10 mg) on day 1. All anacetrapib and warfarin doses were administered with a standard low fat breakfast. After warfarin concentrations and prothrombin time were measured, standard pharmacokinetic, pharmacodynamic and statistical (linear mixed effects model) analyses were applied. Anacetrapib was generally well tolerated when co-administered with warfarin in the healthy males in this study. The geometric mean ratios (GMRs) for warfarin + anacetrapib : warfarin alone and 90% confidence interval (CIs) for warfarin AUC((0-∞)) were 0.94 (0.90, 0.97) for the R(+) warfarin enantiomer and 0.93 (0.87, 0.98) for the S(-) warfarin enantiomer, both being contained in the interval (0.80, 1.25), supporting the primary hypothesis of the study. The GMRs warfarin + anacetrapib : warfarin alone and 90% CIs for the statistical comparison of warfarin C(max) were 1.01 (0.97, 1.05) for both the R(+) warfarin and the S(-) warfarin enantiomers, and were also contained in the interval (0.80, 1.25). The GMR (warfarin + anacetrapib : warfarin alone) and 90% CI for the statistical comparison of INR AUC((0-168 h)) was 0.93 (0.89, 0.96). The single dose pharmacokinetics and pharmacodynamics of orally administered warfarin were not meaningfully affected by multiple dose administration of anacetrapib, indicating that anacetrapib does not affect CYP 2C9 clinically. Thus, no dosage adjustment for warfarin is necessary when co-administered with anacetrapib.


The kappa-opioid U-50,488H suppresses the initiation of nocturnal spontaneous drinking in normally hydrated rats.
The effect of a systemic (IP) treatment with 1.0, 3.0 and 9.0 mg/kg U-50,488H (U50), a highly selective kappa-agonist, on spontaneous, nocturnal ingestive behavior of the rat was studied using a microcomputer controlled data acquisition system. The latency to initiate drinking was increased and drinking behavior was suppressed in the first hour after injection in a dose-dependent manner. The consummatory indices of drinking were not affected. After this period of adipsia, a phase of polydipsia, that was probably due to the diuretic effect of U50, was evident. This prophagic effect of U50 was evident only at the dose of 3 mg/kg and was accompanied by an increased duration of feeding episodes but not by a reduced latency to feed. These results suggest that kappa-receptors play a pivotal role in modulating spontaneous drinking in the normally hydrated rat and that this control is mainly exerted on the motivational aspect of drinking.


The other side of late-life intimacy? Sexual violence in later life.
To explore the extent, nature and consequences of sexual violence in later life. Data were obtained from all police forces in England, Wales and Northern Ireland on rape and sexual assault by penetration (Sexual Offences Act 2003) offences involving a victim aged ≥ 60 years, recorded between 1 January 2009 and 31 December 2013. Qualitative interviews were conducted with 27 practitioners working in specialist violence or age-related organisations and with three female survivors. The majority of victims were female, and most offenders were male. Offenders were generally younger than victims, and most offences occurred in the victim's home, although one in five occurred in a care home. Physical, psychological and social consequences were described which create specific challenges in accessing and receiving support. An intersectional life course analysis of sexual violence is required to develop a better understanding of the consequences, particularly for older women.


Cancer-related disparities: weathering the perfect storm through comprehensive cancer control approaches.
During the last two decades extraordinary progress in developing and using effective cancer prevention strategies, early detection interventions, and cancer treatments has been made. This progress has resulted in an overall decline in mortality rates for all cancers combined. Nonetheless, cancer is the second most common cause of death in the United States. Although cancer is a diagnosis that many survive, cancer experiences across populations may vary considerably. These differences in cancer experiences have created an unequal disease burden that presents distinct professional and moral challenges to our nation. Many cancer control plans suggest specific strategies that prioritize eliminating cancer-related disparities. This article describes certain cancer-related disparities in the United States and gives several examples of how communities and disenfranchised populations are using comprehensive cancer control (CCC) approaches to eliminate these disparities. One or two interventions are highlighted in each example.


Using formaldehyde-assisted isolation of regulatory elements (FAIRE) to isolate active regulatory DNA.
Eviction or destabilization of nucleosomes from chromatin is a hallmark of functional regulatory elements in eukaryotic genomes. Historically identified by nuclease hypersensitivity, these regulatory elements are typically bound by transcription factors or other regulatory proteins. FAIRE (formaldehyde-assisted isolation of regulatory elements) is an alternative approach to identify these genomic regions and has proven successful in a multitude of eukaryotic cell and tissue types. Cells or dissociated tissues are cross-linked briefly with formaldehyde, lysed and sonicated. Sheared chromatin is subjected to phenol/chloroform extraction and the isolated DNA, typically encompassing 1-3% of the human genome, is purified. We provide guidelines for quantitative analysis by PCR, microarrays or next-generation sequencing. Regulatory elements enriched by FAIRE have high concordance with those identified by nuclease hypersensitivity or chromatin immunoprecipitation (ChIP), and the entire procedure can be completed in 3 d. FAIRE has low technical variability, which allows its usage in large-scale studies of chromatin from normal or diseased tissues.


Effect of speed on the energy cost of walking in unilateral traumatic lower limb amputees.
In this work, the effect of walking speed on the energy expenditure in traumatic lower-limb amputees was studied. The oxygen consumption was measured in 10 transfemoral amputees, 9 transtibial amputees and 13 control subjects, while they stood and walked at different speeds from 0.3 m s(-1) to near their maximum sustainable speed. Standing energy expenditure rate was the same in lower-limb amputees and in control subjects (approximately 1.85 W kg(-1)). On the contrary, during walking, the net energy expenditure rate was 30-60% greater in transfemoral amputees and 0-15% greater in transtibial amputees than in control subjects. The maximal sustainable speed was about 1.2 m s(-1) in transfemoral amputees and 1.6 m s(-1) in transtibial amputees, whereas it was above 2 m s(-1) in control subjects. Among these three groups, the cost of transport versus speed presented a U-shaped curve; the minimum cost increased with the level of amputation, and the speed at which this minimum occurred decreased.


A simple and efficient system for the construction of phoA gene fusions in gram-negative bacteria.
We have developed a two-plasmid system for generating gene fusions between phoA and cloned genes encoding envelope proteins. The vector plasmid carries a temperature-sensitive replication system and can be rescued at high temperature by insertion of an IS1-based transposon carrying the ori region of pBR322 and a phoA gene lacking transcription and translation initiation signals. The vector plasmid also carries the transfer origin of the conjugative plasmid, F, permitting transfer into a suitable recipient strain. We have used this system in the analysis of the bla gene cloned from pBR322.


Progression of coronary atherosclerosis from adolescents to mature adults.
Ten selected topographic sites of the coronary arteries were placed in sequence according to age, sex, branching anatomical pattern and smoking habit, in order to obtain an indirect sequencing of the pattern and rate of progression of early atherosclerotic lesions from adolescents to mature adults. The material came from 356 subjects aged 16-45 years who had died in violent accidents and included the light-microscopic examination of 3560 coronary artery samples. The dynamic reconstruction of thousands of static views revealed the existence of an age-related rate of progression of fibromuscular plaques, intimal necrotic areas, incorporated microthrombi and fatty streaks. All these early atherosclerotic lesions increased linearly and in parallel from one 5-year age group to the next and exhibited non-significant differences in their rate of progression over a period of 25 years. During this period the number of atherosclerotic plaques increased 4.7 times, of intimal necrotic areas 4.6 times, of incorporated microthrombi 4.3 times and of fatty streaks 3.9 times. Consequently, in the 10 selected topographic sites of the coronary arteries placed in sequence according to age, the pathological aspects became prevalent, microscopically, over the normal ones, starting from the fourth decade of life. This study also revealed that some endogenous and exogenous risk factors for coronary heart disease accelerated the age-related rate of progression of early atherosclerotic lesions. In addition, particular cycles of evolution towards advanced lesions appeared, leading to the onset of fibronecrotic and fibrohyaline plaques. Their obstructive character was related to both successive incorporation of microthrombi and the onset of large lipid deposits. Among the four types of early atherosclerotic lesions investigated, only the fatty streaks did not show this direct conversion to a lesion of possible clinical significance.


[The role of pelvic exenteration for the treatment of vulvar cancer].
The pelvic exenteration is a method of treatment in cases of recurrence or locally advanced gynecological tumors without distance metastases. The total pelvic exenteration has been used as salvage therapy especially for advanced gynecological malignancy. The aim of study was to analyse the group of women who underwent pelvic exenteration. A series of 13 patients who underwent pelvic exenteration for advanced vulvar cancer at the Department of Gynecology, Medical University of Gdańsk Poland between 1996-2003 was retrospectively reviewed. The more often performed exenteration in patients with vulvar cancer was posterior pelvic exenteration in 11 cases, total pelvic exenteration in 2 cases. The mean age at diagnosis was 56 years. The estimated blood transfusion due to operation ranged from 300 ml to 3580 ml with a mean of 1200 ml. The operating time ranged from 4 hours to 7 hours 30 minutes with a mean of 6 hours and 5 minutes. Patients stayed in hospital from 14 to 54 days after operation with a mean 33 days. The overall complication rate after pelvic exenteration was 61.5% with 8 of the 13 patients. Three times it was infection, six times wound dehiscence, in 1 case it was: ARDS, thrombophlebitis, ureter damage. There was no late complication. Pelvic exenteration offers the last chance for some women with gynecological malignancy.


Electron microscopic findings in four cases of nasopharyngeal fibroma.
Light and electron microscopic investigations of four cases of juvenile nasopharyngeal fibroma revealed characteristic structures; a fibrous stroma, an inclination to hyalinisation and formation of scar like tissue, a lacunar thin walled vascular component, large numbers of mast cells and of fibroblasts. The tumor fibroblasts contained different nuclear bodies and particles. There existed five different types of more or less complex spherical bodies. The previously described nuclear electron dense particles with an electron lucent halo could be divided into four groups measuring 60, 90, 150, and 300 nm in diameter. In addition to the previously described ultrastructural properties of the tumors, the nuclei of the tumor fibroblasts were found to contain virus like particles. These particles were less electron dense, measuring 40 to 55 nm in diameter and arranged in groups throughout the nucleoplasm; they were different from chromatin condensations and from perichromatin granules. The structure and the size of the smallest particles was not comparable with the other nuclear inclusions.


Electronic structure, cohesive and magnetic properties of iridium oxide clusters adsorbed on graphene.
In this study, we investigated and revealed the electronic properties, geometric structures and binding behavior of small (IrO)n and [Formula: see text] (n = 1-5) clusters within first principles calculations based on the density functional theory. The electronic and magnetic properties of small nanoclusters displayed significant size dependency due to strong quantum confinement effect. Moreover we considered the binding and structural modification of the clusters on graphene surface as a substrate. The cohesive energy per atom of isolated clusters increased with size of the cluster n. This shows that the increase in coordination number results in a more stable nanocluster with increased number of saturated bonds. Pristine (IrO)n and [Formula: see text] clusters presented different structural motives at equilibrium. The ground states of (IrO)n and [Formula: see text] clusters considered in this study were all magnetic except for (IrO)4, [Formula: see text] , and [Formula: see text] . HOMO-LUMO gap EHLG values displayed large variations due to size of the cluster, hence bond saturation. The structural configurations of free standing nanoclusters are slightly modified, when adsorbed on graphene. The adsorption behavior of a cluster on graphene was improved by an applied electric field yielding larger binding energy and larger charger transfer. We observed that electronic and magnetic ground state of the clusters strongly depend on optimized structural configuration for both bare and adsorbed on graphene monolayer.


Humans use continuous visual feedback from the hand to control fast reaching movements.
How visual feedback contributes to the on-line control of fast reaching movements is still a matter of considerable debate. Whether feedback is used continuously throughout movements or only in the "slow" end-phases of movements remains an open question. In order to resolve this question, we applied a perturbation technique to measure the influence of visual feedback from the hand at different times during reaching movements. Subjects reached to touch targets in a virtual 3D space, with visual feedback provided by a small virtual sphere that moved with a subject's fingertip. Small random perturbations were applied to the position of the virtual fingertip at two different points in the movement, either at 25% or 50% of the total movement extent. Despite the fact that subjects were unaware of the perturbations, their hand trajectories showed smooth and accurate corrections. Detectable responses were observed within an average of 160 ms after perturbations, and as early as 60% of the distance to the target. Response latencies were constant across different perturbation times and movement speed conditions, suggesting that a fixed sensori-motor delay is the limiting factor. The results provide direct evidence that the human brain uses visual feedback from the hand in a continuous fashion to guide fast reaching movements throughout their extent.


Enterovirus 71 isolated from cases of epidemic poliomyelitis-like disease in Bulgaria.
Virological and serological studies of an epidemic disease in Bulgaria, 1975, were carried out. Epidemiologically, clinically and pathomorphologically, the disease simulated almost all known forms of poliomyelitis, acute stem encephalitis, encephalomyocarditis and aseptic meningitis. The studies completely rules out the participation of polioviruses and provided comprehensive evidence for the etiological role of a peculiar enterovirus subsequently identified as enterovirus (EV) type 71 known in the literature since 1974. Altogether, in 1975 and 1976 from 65 cases of poliomyelitis-like disease (PLD) 92 strains of EV71 were isolated, including 37 strains from the brain and medulla, 1 from the cerebrospinal fluid, 10 from mesenterial lymph nodes and tonsils and 44 from faeces. In addition, in 282 convalescent cases of the disease, diagnostic seroconversion or high titers of antibody to this virus were demonstrated. The most successful virus isolation was achieved by inoculation of green monkey kidney cell cultures and newborn white mice. Bulgarian strains of enterovirus 71 regularly caused paralysis in monkeys and morphological poliomyelitis-like lesions in their CNS, and paralysis and myositis with Zenker necrosis in newborn white mice, cotton rats, Syrian hamsters, and 3-week-old cotton rats. The diseased rodents had much more virus in their mucles than in brains.


Magnetic resonance imaging of the clivus and its age-related changes in the bone marrow.
The clivus is a bone region between dorsum cella and foramen magnum. It can be evaluated very clearly in routine brain magnetic resonance imaging (MRI) dueto its central location. Quantitative and qualitative evaluation of the clivus and its changes according to age in a group of healthy people. The transition of clival bone marrow to fatty marrow by the increasein age is examined by MRI in 105 men and 105 women who had no clival and bone marrow pathology on MRI. The clivus/pons, clivus/CSF intensity values and clival bone marrow imaging patterns according to age groups were prospectively evaluated using a 1.5 Tesla MR device. When age groups were individually compared, there were meaningful statistical differences both in men and women in terms of clivus/CSF and clivus/pons intensity ratios (both Ps < 0.05). Clivus/pons and clivus/CSF intensity ratios were found to be increased with age in all cases. The distribution of age groups according to stages in all individuals was statistically meaningful (P < 0.05). When the appearance patterns of both genders in every ten-fold age were examined, stage III bone marrow was observed more in elder ages. As a result, besides the fact that standard ranges determined for clivus/CSF, clivus/pons intensity ratios according to age may be used in the assessment of potential pathological cases involving bone marrow; they can also be leading in the diagnosis of bone marrow diseases when taken into consideration together with clinical and laboratory data.


Identification of opposites and intermediates by eye and by hand.
In this eye-tracking and drawing study, we investigate the perceptual grounding of different types of spatial dimensions such as dense-sparse and top-bottom, focusing both on the participants' experiences of the opposite regions, e.g., O1: dense; O2: sparse, and the region that is experienced as intermediate, e.g., INT: neither dense nor sparse. Six spatial dimensions expected to have three different perceptual structures in terms of the point and range nature of O1, INT and O2 were analysed. Presented with images, the participants were instructed to identify each region (O1, INT, O2), first by looking at the region, and then circumscribing it using the computer mouse. We measured the eye movements, identification times and various characteristics of the drawings such as the relative size of the three regions, overlaps and gaps. Three main results emerged. Firstly, generally speaking, intermediate regions were not different from the poles on any of the indicators: overall identification times, number of fixations, and locations. Some differences emerged with regard to the duration of fixations for point INTs and the number of fixations for range INTs between two range poles (O1, O2). Secondly, the analyses of the fixation locations showed that the poles support the identification of the intermediate region as much as the intermediate region supports the identification of the poles. Finally, the relative size of the three areas selected in the drawing task were consistent with the classification of the regions as points or ranges. The analyses of the gaps and the overlaps between the three areas showed that the intermediate is neither O1 nor O2, but an entity in its own right.


Focal cortical dysplasia links to sleep-related epilepsy in symptomatic focal epilepsy.
In sleep-related epilepsy (SRE), epileptic seizures predominantly occur during sleep, but the clinical characteristics of SRE remain elusive. We aimed to identify the clinical features associated with the occurrence of SRE in a large cohort of symptomatic focal epilepsy. We retrospectively included patients with four etiologies, including focal cortical dysplasia (FCD), low-grade tumors (LGT), temporal lobe epilepsy with hippocampal sclerosis (TLE-HS), and encephalomalacia. SRE was defined as more than 70% of seizures occurring during sleep according to the seizure diary. The correlation between SRE and other clinical variables, such as etiology of epilepsy, pharmacoresistance, seizure frequency, history of bilateral tonic-clonic seizures, and seizure localization was analyzed. A total of 376 patients were included. Among them 95 (25.3%) were classified as SRE and the other 281(74.7%) as non-SRE. The incidence of SRE was 53.5% in the FCD group, which was significantly higher than the other three groups (LGT: 19.0%; TLE-HS: 9.9%; encephalomalacia: 16.7%; P < 0.001). The etiology of FCD (p < 0.001) was significantly associated with SRE (OR: 9.71, 95% CI: 3.35-28.14) as an independent risk factor. In addition, small lesion size (p = 0.009) of FCD further increased the risk of SRE (OR: 3.18, 95% CI: 1.33-7.62) in the FCD group. Our data highlight that FCD markedly increased the risk of sleep-related epilepsy independently of seizure localization. A small lesion of FCD further increased the risk of sleep-related epilepsy by 2.18 times in the FCD group.


Comparative effects of captopril and isosorbide dinitrate on pulmonary arteriolar resistance and right ventricular function in patients with severe left ventricular failure: results of a randomized crossover study.
We compared the short-term hemodynamic effects of isosorbide dinitrate (40 mg orally) and captopril (25 mg orally) in 18 patients with severe chronic heart failure in a randomized, crossover study conducted on consecutive days. Captopril and isosorbide dinitrate produced similar decreases in systemic vascular resistance, but whereas nitrate therapy decreased pulmonary arteriolar resistance significantly, captopril did not; the difference between the two drugs was highly significant (-25% vs -5%, p less than 0.001). Left ventricular filling pressures declined similarly with both captopril (-10.5 mm Hg) and with isosorbide dinitrate (-9.3 mm Hg), but because pulmonary arteriolar resistance fell significantly with nitrate therapy, mean right atrial pressure decreased more with isosorbide dinitrate than with captopril (-5.4 vs -2.8 mm Hg, respectively; p less than 0.001). Although systemic resistance declined similarly with both drugs, cardiac index increased more with nitrate therapy than during converting-enzyme inhibition (+0.47 vs +0.23 L/min/m2) (p less than 0.01), and therefore mean arterial pressure fell less with isosorbide dinitrate than with captopril (-10.5 mm Hg vs -16.7 mm Hg); p less than 0.05); two patients developed symptomatic hypotension with captopril, whereas none did so with the nitrate. The difference in the effects of the two drugs on cardiac index was not due to differences in their effects on heart rate, since heart rate fell similarly with both drugs, and thus both drugs produced similar increases in stroke volume index. These data indicate that, in patients with severe chronic heart failure, nitrates exert favorable dilating effects on the pulmonary circulation not shared by captopril.(ABSTRACT TRUNCATED AT 250 WORDS)


Genome-wide association mapping of preharvest sprouting resistance in a diversity panel of European winter wheats.
Global wheat production will benefit from cultivars showing genetic resistance to preharvest sprouting (PHS). Working on PHS resistance is still challenging due to the lack of simple protocols for the provocation of symptoms for appropriate trait differentiation under highly variable environmental conditions. Therefore, the availability of molecular markers for enhancing PHS resistance in breeding lines is of utmost importance. Genome-wide association mapping was performed to unravel the genetics of PHS resistance in a diversity panel of 124 winter wheat genotypes using both random and targeted marker locus approaches. Data for grain germination tests, spike wetting treatments, and field sprouting damage measurements of grains were collected in 11, 12, and four environments, respectively. Twenty-two quantitative trait loci (QTL) linked with 40 markers were detected for the three traits commonly used for assessing the PHS resistance of cultivars. All but five QTL on chromosomes 1B, 1D (two QTL), 3D, and 5D showed locations similar to previous studies, including prominent QTL on chromosomes 2BS, 3AS, and 4AL. The highest retrieval rate across environments was found for QTL on chromosomes 1D, 2BS, 3D, 4AL, and 7B. The study identified genomic signatures useful for marker-assisted improvement of PHS resistance not only in European breeding programs, but of global significance.


Economic change, alcohol consumption and heart disease mortality in nine industrialized countries.
This paper examines the question of whether economic changes--including economic growth, unemployment and business failures--and alcohol consumption by beverage type are independently related to heart disease mortality. Controls for cigarette and animal fat consumption are also employed in a multivariate time series analysis. Data for nine countries in the post World War II era are investigated: Australia, Canada, England and Wales, Denmark, Federal Republic of Germany, Finland, France, Sweden and the United States. In all nine countries unemployment and business failures are positively related to heart disease mortality, and in eight countries the trend of economic growth shows an inverse relationship. The relation of alcohol consumption to heart disease mortality depends on beverage type. When spirits or wine consumption shows a significant relation, occasionally requiring controls for other beverages, it is positive. On the other hand, beer consumption shows an inverse relation to heart disease mortality in all countries. The statistical significance of that relationship also occasionally must be based on controls for other beverages.


Is there value in alvimopan in minimally invasive colorectal surgery?
Alvimopan's goal is to minimize postoperative ileus and optimize outcomes; however, evidence in laparoscopic surgery is lacking. Our goal was to evaluate the benefit of alvimopan in laparoscopic colorectal surgery with an enhanced recovery pathway (ERP). Laparoscopic colorectal cases were stratified into alvimopan and control cohorts, then case-matched for comparability. All followed an identical ERP. The main outcomes were length of stay, complications, readmissions, and costs in the alvimopan and control groups. About 321 patients were analyzed in each cohort. Operative times were comparable (P = .08). Postoperatively, complication rates were similar (P = .29), with no difference in ileus (P = 1.00). The length of stay (3.69 vs 3.49 days; P = .16), readmission (2.8% vs 3.7%; P = .66) and reoperation rates (2.2% vs 1.6%; P = .77) were comparable for alvimopan and controls, respectively. Total costs were similar ($14,932.47 alvimopan vs $14,846.56 controls; P = .90), but the additional costs in the alvimopan group could translate to savings of $27,577 in the cohort. Alvimopan added no benefit in patient outcomes in laparoscopic colorectal surgery with an ERP. These results could drive a change in current practice. Controlled studies are warranted to define the cost and/or benefit in clinical practice.


Effect of acute ethanol administration on S-amino acid metabolism: increased utilization of cysteine for synthesis of taurine rather than glutathione.
Alterations in the hepatic metabolism of S-amino acids were examined in male rats injected with a single dose of ethanol (3 g/kg, i.p.). The hepatic concentrations of methionine and S-adenosylhomocysteine (SAH) were increased, but S-adenosylmethionine (SAM), cysteine, and glutathione (GSH) decreased rapidly following ethanol administration. The activities of methionine adenosyltransferase (MAT), cystathionine beta-synthase (CbetaS) and cystathionine gamma-lyase (CgammaL) were all inhibited. Gamma-glutamylcysteine synthetase (GCS) activity was increased from t = 8 hr, but hepatic glutathione (GSH) level did not return to control for 48 hr. Both hepatic hypotaurine and taurine levels were increased immediately, which were reduced to below control from t = 18 hr. Changes in the serum concentration of taurine were consistent with results observed in the liver. Cysteine dioxygenase (CDO) activity was increased rapidly, but declined from t = 24 hr. The results indicate that an acute dose of ethanol induces significant alterations in the metabolism of S-amino acids in the liver. Ethanol depresses the cysteine availability for GSH synthesis not only by inhibiting the transsulfuration reactions but also by enhancing its irreversible catabolism to taurine via hypotaurine. The physiological significance of this finding is discussed.


Metformin inhibits cell proliferation in SKM-1 cells via AMPK-mediated cell cycle arrest.
Metformin, a widely used antidiabetic drug, has previously been demonstrated to exert anti-cancer effects in certain hematological malignancies, but its effects on the transformation of myelodysplastic syndromes to acute myeloid leukemia (AML-MDS) remain unclear. The present study aimed to investigate the effects of metformin on SKM-1 cells (an AML-MDS cell line) and its underlying mechanisms. SKM-1 cells were treated with different concentrations of metformin. Cell proliferation was assayed by CCK-8. Apoptosis and cell cycle phases were detected by flow cytometry, while cell cycle related proteins and AMPK were tested by Western blot. SKM-1 cells were transfected with LV-AMPKα1-RNAi to reduce the expression of AMPK. Metformin inhibited cell proliferation in a dose and time dependent manner by inducing G0/G1 phase arrest rather than apoptosis induction. Metformin promoted the expression of p-AMPK, P53, P21CIP1 and P27KIP1, while inhibited the expression of CDK4 and CyclinD1. AMPK knockdown attenuated the effects of metformin on SKM-1 cells. These findings suggested that metformin inhibited proliferation of SKM-1 cells, potentially through an AMPK-mediated cell cycle arrest.


Disseminated Mycobacterium avium infection in a patient with a novel mutation in the interleukin-12 receptor-beta1 chain.
A girl with relapsing cervical lymphadenopathy due to Mycobacterium avium subsequently developed abdominal adenopathy and intestinal inflammation. 1 known (c.1623_1624delGCinsTT) and 1 novel mutation (c.65_68delCTGC of exon2) of the Interleukin-12 Receptor-beta1 (IL-12Rbeta1) gene was detected. Unlike reports of a more favorable outcome in these patients, our patient died of severe intestinal involvement.


The role of intratumour therapy with electroporation and bleomycin in the management of advanced squamous cell carcinoma of the head and neck.
To determine the safety and efficacy of electroporation with bleomycin in patients with advanced squamous cell carcinoma of the head and neck. Two open-label, multicenter, single-arm Phase II studies of intratumour electroporation therapy. Sixty-two patients with 86 squamous cell carcinoma tumours of the head and neck were enrolled. Twenty-five patients were treated with bleomycin alone. Fifty-four patients (17 initially treated with bleomycin alone) were treated with electroporation and bleomycin therapy. Local tumour response was measured. In the bleomycin alone group, one tumour showed a partial response and 36 tumours showed no response to treatment. In the bleomycin with electroporation groups, 17 tumours showed complete response, 22 tumours showed partial response and 30 failed to achieve more than a 50% reduction in tumour size (no response). Bleomycin with electroporation had a significantly (p<0.001) greater number of patients showing a partial or complete response to the therapy when compared to bleomycin alone. Thirteen adverse events were reported which included five episodes of local bleeding, six local infections, one local tongue swelling and one cardiac arrhythmia. Fifty-seven percent of squamous cell carcinomas of the head and neck demonstrated a partial or complete response to intratumour electroporation with bleomycin suggesting that further work investigating its use as a treatment for local control of these lesions should be pursued.