Author Correction: The role of sex in the genomics of human complex traits.
In Box 4 of the originally published article, the text describing the Miami plot in part c of the figure contained some minor errors. Specifically, during pre-publication revision of the article, the authors updated the illustrative Miami plot (shown in figure part c) from that of reference 80 (Randall et al. PLoS Genet. (2013)) to a more recent study in reference 82 (Winkler et al. PLoS Genet. (2015)). The box text has now been updated to reflect that change. In paragraph 2, the trait has been updated from "hip circumference adjusted for body mass index" to "waist-to-hip ratio adjusted for body mass index (under 50 years old)" and it has been clarified that female GWAS data are shown on the top half of the plot with male data at the bottom. The original two citations of reference 80 in the Box 4 text have been updated to reference 82. Finally, a typographical artefact was corrected on the Y axis of the Miami plot, whereby the labels '14' and '16' in the top half of the plot we originally both shown as '12'. None of these corrections alter the overall illustrative point that genetic architectures for traits can differ between males and females, which was a conclusion of both reference 80 and reference 82.


What's love got to do with jealousy?
Romantic love and jealousy seem antagonistic, but the expression of both emotions have evolutionary functions that can go in the same direction of maintaining a relationship. Considering natural selection designed adaptations to solve the problems surrounding reproduction, then love and romantic jealousy are emotions aimed at staying cooperative for a period of time, where love solves the adaptive challenges of promoting pair bonding, cooperation, and protecting offspring; and jealousy is triggered by a threat or the loss of a valuable cooperative relationship, either on behalf of descendants in need of resources, or a close romantic bond. Consequently, understanding love and romantic jealousy points in the same adaptive functional domain of protecting a romantic pair bond. Specifically, love can be comprehended in two different ways and in regard to jealousy. First, conceiving love as the attachment to significant others one develops throughout lifetime, and secondly, it contemplates affective dependence. Results from a sample of single and committed individuals (n = 332) show the predicted positive correlation between attachment and jealousy as stable traits, consistent with previous literature. In addition, there is a non-significant and low correlation, respectively, between attachment and love as a measure of dependence. Furthermore, in the single participants group, jealousy was associated with love. The discussion emphasizes the need for expanding a functional account of love and jealousy as complementary emotions of our human affective endowment. Finally, it would be informative to study attachment as a relational trait and love as a specific affection for a romantic partner that could be manipulated to elucidate the functional design of jealousy.


Selection of reference genes for quantitative RT-PCR studies in striped dolphin (Stenella coeruleoalba) skin biopsies.
Odontocete cetaceans occupy the top position of the marine food-web and are particularly sensitive to the bioaccumulation of lipophilic contaminants. The effects of environmental pollution on these species are highly debated and various ecotoxicological studies have addressed the impact of xenobiotic compounds on marine mammals, raising conservational concerns. Despite its sensitivity, quantitative real-time PCR (qRT-PCR) has never been used to quantify gene induction caused by exposure of cetaceans to contaminants. A limitation for the application of qRT-PCR is the need for appropriate reference genes which allow the correct quantification of gene expression. A systematic evaluation of potential reference genes in cetacean skin biopsies is presented, in order to validate future qRT-PCR studies aiming at using the expression of selected genes as non-lethal biomarkers. Ten commonly used housekeeping genes (HKGs) were partially sequenced in the striped dolphin (Stenella coeruleoalba) and, for each gene, PCR primer pairs were specifically designed and tested in qRT-PCR assays. The expression of these potential control genes was examined in 30 striped dolphin skin biopsy samples, obtained from specimens sampled in the north-western Mediterranean Sea. The stability of selected control genes was determined using three different specific VBA applets (geNorm, NormFinder and BestKeeper) which produce highly comparable results. Glyceraldehyde-3P-dehydrogenase (GAPDH) and tyrosine 3-monooxygenase (YWHAZ) always rank as the two most stably expressed HKGs according to the analysis with geNorm and Normfinder, and are defined as optimal control genes by BestKepeer. Ribosomal protein L4 (RPL4) and S18 (RPS18) also exhibit a remarkable stability of their expression levels. On the other hand, transferrin receptor (TFRC), phosphoglycerate kinase 1 (PGK1), hypoxanthine ribosyltransferase (HPRT1) and beta-2-microglobin (B2M) show variable expression among the studied samples and appear as less suitable reference genes for data normalization. In this work, we have provided essential background information for the selection of control genes in qRT-PCR studies of cetacean skin biopsies, as a molecular technique to investigate ecotoxicological hazard in marine mammals. Of 10 HKGs tested, those encoding for YWHAZ and GAPDH appear as the most reliable control genes for the normalization of qRT-PCR data in the analysis of striped dolphin skin biopsies. Potentially useful reference genes are also those encoding for ribosomal proteins L4 and S18.


An Artificial Pathway for N-Hydroxy-Pipecolic Acid Production From L-Lysine in Escherichia coli.
N-hydroxy-pipecolic acid (NHP) is a hydroxylated product of pipecolic acid and an important systemic acquired resistance signal molecule. However, the biosynthesis of NHP does not have a natural metabolic pathway in microorganisms. Here, we designed and constructed a promising artificial pathway in Escherichia coli for the first time to produce NHP from biomass-derived lysine. This biosynthesis route expands the lysine catabolism pathway and employs six enzymes to sequentially convert lysine into NHP. This artificial route involves six functional enzyme coexpression: lysine α-oxidase from Scomber japonicus (RaiP), glucose dehydrogenase from Bacillus subtilis (GDH), Δ1-piperideine-2-carboxylase reductase from Pseudomonas putida (DpkA), lysine permease from E. coli (LysP), flavin-dependent monooxygenase (FMO1), and catalase from E. coli (KatE). Moreover, different FMO1s are used to evaluate the performance of the produce NHP. A titer of 111.06 mg/L of NHP was yielded in shake flasks with minimal medium containing 4 g/L of lysine. By this approach, NHP has so far been produced at final titers reaching 326.42 mg/L by 48 h in a 5-L bioreactor. To the best of our knowledge, this is the first NHP process using E. coli and the first process to directly synthesize NHP by microorganisms. This study lays the foundation for the development and utilization of renewable resources to produce NHP in microorganisms.


A smart "strider" can float on both water and oils.
Aquatic devices that can work on both water and oils have great scientific and practical significance, but the challenge remains in developing novel materials with excellent repellence to both water and oils. Here, we report that an artificial "strider" can float on both water and oils by using supporting legs with ultraviolet (UV) switchable wettability. The legs were fabricated by immobilizing TiO2 nanoparticles and n-dodecanethiol onto copper foams via a simple mussel-inspired process. At ambient conditions, the strider floated freely on a water surface, but it dived in water and then stood stably at the interface of water/CHCl3 after UV illumination for 2 h. The reason for this unique behavior is that the legs changed their wettability from superhydrophobicity to underwater superoleophobicity after the illumination. It was revealed that the micro/nanohierarchical structures and photosensitivity of the immobilized TiO2 nanoparticles accounted for the switchable wettability and large supporting force of the legs. The findings of this study offer an alternative strategy for fabricating smart aquatic devices that might be used for water environment protection, water resource surveillance, oil spill cleanup, and so on.


Combined use of sodium hyaluronate and tissue adhesive in penetrating keratoplasty of corneal perforations.
A new technique which allows the use of a guarded trephine in penetrating keratoplasty for corneal perforation is described. It involves the combined use of cyanoacrylate adhesive and sodium hyaluronate and allows a normotensive eye to be obtained prior to trephination. Five cases in which this technique was used are described. A better tectonic result can be obtained and visual rehabilitation may be more readily achieved without performing a secondary procedure.


Lenalidomide and Temozolomide Combination in a Very Elderly Patient with CNS Relapse of Diffuse Large B-Cell Lymphoma.
Central nervous system (CNS) relapse is an infrequent but severe complication for DLBCL patients, associated with poor prognosis. Intravenous prophylaxis with high-dose methotrexate has shown promising results but is rarely feasible in elderly and/or nephropathic patients. A 83 years old woman with CNS relapse occurred 6 months after chemoimmunotherapy. The patient was defined ineligible for radiotherapy (RT) and started oral Temozolomide 250mg daily for 5 consecutive days without any improvement after 1st cycle. We administered lenalidomide 25mg daily for 21 days every 28 days together with temozolomide 250mg daily for 5 days every 28 days. The patient experienced a rapid improvement of general and cognitive conditions; Gadolinium-enhanced brain MRI showed a wide reduction of neoplastic tissue. The patients maintained good clinical conditions with mild treatment toxicity until the end of the 6th cycle, when brain MRI showed disease progression and the patient died 1 month later. We suggest lenalidomide could be a feasible option for CNS relapse in elderly DLBCL patients and it could be associated in future studies with other cytotoxic agents such as temozolomide.


[Mesotherapy in trichology].
Mesotherapy (from Greek meso = in between, therapeia = treat) is a non-surgical, mostly cosmetic therapy, where active substances are injected intradermally into a depth of about 4 mm. It is an effective and easy-to-use method in the treatment of alopecia. It is effective both in the therapy of androgenetic alopecia and telogen effluvium. In recent years, it has been massively expanded also among non-medical fields, which has caused its contradictory perception by professional medical circles outside dermatologists. This article summarizes the possible therapeutic use of mesotherapy using vitamins, trace elements and stem cell extracts. Their effect has been demonstrated in a number of clinical trials.


Personalized ctDNA micro-panels can monitor and predict clinical outcomes for patients with triple-negative breast cancer.
Circulating tumor DNA (ctDNA) in peripheral blood has been used to predict prognosis and therapeutic response for triple-negative breast cancer (TNBC) patients. However, previous approaches typically use large comprehensive panels of genes commonly mutated across all breast cancers. Given the reduction in sequencing costs and decreased turnaround times associated with panel generation, the objective of this study was to assess the use of custom micro-panels for tracking disease and predicting clinical outcomes for patients with TNBC. Paired tumor-normal samples from patients with TNBC were obtained at diagnosis (T0) and whole exome sequencing (WES) was performed to identify somatic variants associated with individual tumors. Custom micro-panels of 4-6 variants were created for each individual enrolled in the study. Peripheral blood was obtained at baseline, during Cycle 1 Day 3, at time of surgery, and in 3-6 month intervals after surgery to assess variant allele fraction (VAF) at different timepoints during disease course. The VAF was compared to clinical outcomes to evaluate the ability of custom micro-panels to predict pathological response, disease-free intervals, and patient relapse. A cohort of 50 individuals were evaluated for up to 48 months post-diagnosis of TNBC. In total, there were 33 patients who did not achieve pathological complete response (pCR) and seven patients developed clinical relapse. For all patients who developed clinical relapse and had peripheral blood obtained ≤ 6 months prior to relapse (n = 4), the custom ctDNA micro-panels identified molecular relapse at an average of 4.3 months prior to clinical relapse. The custom ctDNA panel results were moderately associated with pCR such that during disease monitoring, only 11% of patients with pCR had a molecular relapse, whereas 47% of patients without pCR had a molecular relapse (Chi-Square; p-value = 0.10). In this study, we show that a custom micro-panel of 4-6 markers can be effectively used to predict outcomes and monitor remission for patients with TNBC. These custom micro-panels show high sensitivity for detecting molecular relapse in advance of clinical relapse. The use of these panels could improve patient outcomes through early detection of relapse with preemptive intervention prior to symptom onset.


Neuropathic pain and quality of life after wide local excision and sentinel lymph node biopsy for melanoma: a multicentre study.
Wide local excision and sentinel lymph node biopsy is the mainstay of treatment for patients with melanoma. As survival outcomes improve, longer term quality of life questions become more pertinent and this study aims to assess the factors which may play a role following surgery. A total of, 221 patients who underwent wide local excision and sentinel lymph node biopsy for melanoma (AJCC stage I and II) were recruited from three UK centres. These patients completed a patient outcome questionnaire, which included demographic and treatment data as well as quality of life and pain questionnaires. Pain was the only significant factor influencing the quality of life with a negative correlation seen between pain and quality of life scores (P<0.001). In total, 34% of patients reported pain at their surgical site and four (1.8%) patients scored as high risk for neuropathic pain. Patients experiencing pain were significantly younger that those not reporting pain (median 55.0 vs. 63.5 years, P<0.001). Length of time since surgery did not correlate with pain nor quality of life scores. Our results suggest that following this common procedure a sizeable proportion of patients experience pain and poorer quality of life which does not improve with time. The level of pain experienced is clinically significant and merits evaluation and treatment in this group of patients who are increasingly surviving their melanoma diagnosis. Further investigation into potential prophylactic measures is suggested.


Neurosyphilis Initially Misdiagnosed as Behavioral Variant Frontotemporal Dementia: Life-Changing Differential Diagnosis.
Diagnosing neurosyphilis can be challenging and it may be misdiagnosed as behavior variant frontotemporal dementia, given its affinity for the frontal and temporal lobes. Here we present a model case, who, in his 40 s, was initially misdiagnosed with behavioral variant frontotemporal dementia based on extreme self-neglect and disinhibition over six months and frontal lobe atrophy. He was later diagnosed as neurosyphilis with positive syphilis tests in his cerebrospinal fluid. He underwent penicillin treatment and fully recovered. Relatively rapid cognitive decline, particularly if young, should prompt physicians to consider neurosyphilis as a treatable dementia, which could completely change a patient's life.


A high-throughput skim-sequencing approach for genotyping, dosage estimation and identifying translocations.
The development of next-generation sequencing (NGS) enabled a shift from array-based genotyping to directly sequencing genomic libraries for high-throughput genotyping. Even though whole-genome sequencing was initially too costly for routine analysis in large populations such as breeding or genetic studies, continued advancements in genome sequencing and bioinformatics have provided the opportunity to capitalize on whole-genome information. As new sequencing platforms can routinely provide high-quality sequencing data for sufficient genome coverage to genotype various breeding populations, a limitation comes in the time and cost of library construction when multiplexing a large number of samples. Here we describe a high-throughput whole-genome skim-sequencing (skim-seq) approach that can be utilized for a broad range of genotyping and genomic characterization. Using optimized low-volume Illumina Nextera chemistry, we developed a skim-seq method and combined up to 960 samples in one multiplex library using dual index barcoding. With the dual-index barcoding, the number of samples for multiplexing can be adjusted depending on the amount of data required, and could be extended to 3,072 samples or more. Panels of doubled haploid wheat lines (Triticum aestivum, CDC Stanley x CDC Landmark), wheat-barley (T. aestivum x Hordeum vulgare) and wheat-wheatgrass (Triticum durum x Thinopyrum intermedium) introgression lines as well as known monosomic wheat stocks were genotyped using the skim-seq approach. Bioinformatics pipelines were developed for various applications where sequencing coverage ranged from 1 × down to 0.01 × per sample. Using reference genomes, we detected chromosome dosage, identified aneuploidy, and karyotyped introgression lines from the skim-seq data. Leveraging the recent advancements in genome sequencing, skim-seq provides an effective and low-cost tool for routine genotyping and genetic analysis, which can track and identify introgressions and genomic regions of interest in genetics research and applied breeding programs.


Feasibility of dual radionuclide brain imaging with I-123 and Tc-99m.
A study was conducted to evaluate the feasibility of simultaneous dual radionuclide brain imaging with 123I and 99mTc using photopeak image subtraction techniques or offset photopeak image acquisition. The contribution of the photons from one radionuclide to a second radionuclide's photopeak energy window (crosstalk) was evaluated for SPECT and planar imaging of a brain phantom containing 123I and 99mTc for a range of activity levels and distribution properties approximating those in rCBF images of the adult human brain. Crosstalk was evaluated for 10% symmetrical energy windows centered on the 123I and 99mTc photopeaks and for 10% energy windows asymmetrically placed to the left and right of the center of the respective photopeaks. Major observations include: (1) in the centered photopeak windows, 99mTc crosstalk in the 123I window is 8.9% of the 99mTc seen in the 99mTc window and ranges from 37.5% to 75.0% of the 123I in the 123I window. 123I crosstalk is 37.8% of the 123I seen in the 123I window and ranges from 4.4% to 8.9% of the 99mTc seen in the 99mTc window; (2) the spatial distribution of a radionuclide's crosstalk photons differs from that observed in the radionuclide's photopeak window; (3) a 99mTc photopeak window offset to the left does not decrease 123I crosstalk, and the percentage of 99mTc scattered photons is significantly increased in the window.(ABSTRACT TRUNCATED AT 250 WORDS)


Methylenetetrahydrofolate Reductase C677T: Hypoplastic Left Heart and Thrombosis.
The incidence of congenital heart defects is higher in infants with mutation of methylenetetrahydrofolate reductase (MTHFR) gene. The MTHFR C677T gene decreases the bioavailability of folate and increases plasma homocysteine, a risk factor for thrombosis. There have been no reported cases in the literature on the clinical implications of this procoagulable state in the setting of cyanotic heart disease, which itself has prothrombotic predisposition. Two patients with hypoplastic left heart syndrome developed postoperative thrombotic complications, both were homozygous for MTHFR C677T. We present these cases and highlight the implications of MTHFR mutation in the management of complex congenital heart disease.


Palladium mesowire arrays for fast hydrogen sensors and hydrogen-actuated switches.
Arrays of mesoscopic palladium wires prepared by electrodeposition form the basis for hydrogen sensors and hydrogen-actuated switches that exhibit a response time ranging from 20 ms to 5 s, depending on the hydrogen concentration. These devices were constructed by electrodepositing palladium mesowires on a highly oriented pyrolytic graphite surface and then transferring these mesowires to a cyanoacrylate film supported on a glass slide. The application of silver contacts to the ends of 10-100 mesowires, arrayed electrically in parallel, produced sensors and switches that exhibited a high conductivity state in the presence of hydrogen and a low conductivity state in the absence of hydrogen. After an initial exposure to hydrogen, 15-50 nanoscopic gaps are formed in each mesowire. These nanoscopic gaps or "break junctions" close in the presence of hydrogen gas and reopen in its absence as hydrogen is reversibly occluded by the palladium grains in each wire, and the palladium lattice expands and contracts by several percent. The change in resistance for sensors and switches was related to the hydrogen concentration over a range from 1 to 10%.


Chitosan-Biotin-Conjugated pH-Responsive Ru(II) Glucose Nanogel: A Dual Pathway of Targeting Cancer Cells and Self-Drug Delivery.
The current study paves the way for improved chemotherapy by creating pH-responsive nanogels (NGs) (GC1 and GC2) loaded with synthetic ruthenium(II) arene complexes to increase biological potency. NGs are fabricated by the conjugation of chitosan (CTS)-biotin biopolymers that selectively target the cancer cells as CTS has the pH-responsive property, which helps in releasing the drug in cancer cells having pH ∼ 5.5, and biotin provides the way to target the cancer cells selectively due to the overexpression of integrin. The synthesized compounds and NGs were thoroughly characterized using various spectroscopic and analytical techniques such as NMR, electrospray ionization-mass spectrometry, Fourier transform infrared, UV-vis, scanning electron microscopy, transmission electron microscopy, X-ray photoelectron spectroscopy, rheology, Brunauer-Emmett-Teller, and others. NGs displayed exceptional increased efficacy toward cancerous cells with IC50 values ranging from 7.50 to 18.86 μM via induced apoptosis in three human cancer cell lines. Apart from its potency, NGs were found to be highly selective toward cancer cells. Moreover, based on the results of immunoblot analysis, it was observed that the synthesized compounds exhibit a significant increase in the expression of cleaved caspase-3 and a decrease in the expression of the antiapoptotic protein BCL-XL. Interestingly, the complexes were discovered to have the additional capability of catalyzing the conversion of NADH to NAD+, leading to the generation of radical oxygen species within the cells. Additionally, it was discovered that NG-induced apoptosis depends on ROS production and DNA binding. A narrower range of LD50 values (1185.93 and 823.03 μM) was seen after administering NGs to zebrafish embryos in vivo. The results support the use of drug-loaded NGs as potential chemotherapeutic and chemopreventive agents for human cancer cells.


Origins of tooth pulp-evoked far-field and early near-field potentials in the cat.
Electrical stimulation of the mandibular canine tooth pulp in barbiturate-anesthetized cats activated myelinated A-beta-fibers in the inferior alveolar (dental) nerve and evoked a complex pattern of short-latency potentials that were recorded epidurally from the cortex. Three far-field components ( FFPs designated I, IIa,b, and IIIa,b) and two early near-field components ( ENFPs designated P1 and N1) were identified from computer-averaged potentials recorded over the contralateral lateral sigmoid gyrus or ipsilateral presylvian /anterior coronal gyri. Several corroborative lines of evidence indicated that tooth pulp-evoked FFPs and ENFPs originate from the following generator sources: I, inferior alveolar (dental) nerve/semilunar (gasserian) ganglion; IIa,b, trigeminal lemniscal fibers from the principal (main) sensory nucleus; IIIa,b, thalamocortical fibers from the thalamic ventral posteromedial nucleus; P1, N1, cytoarchitectural area 3 on the banks of the coronal or orbital sulcus. The latencies and waveforms of volume-conducted, surface-recorded potentials were not significantly different from those recorded at putative generator sites along the trigeminal lemniscal projection system. The short latencies and distribution of surface- and depth-recorded tooth pulp-evoked potentials suggested bilateral, trisynaptic paths from peripheral nerve to cortical neurons. Amplitude measurements of FFPs and ENFPs recorded at the cortical, epidural surface were compared to calculated values based on a mathematical model of two concentric spheres of inhomogeneous media in which a single equivalent dipole is radially oriented at some distance from the center. The morphology and distribution of FFPs and ENFPs are discussed in relationship to source geometry. Surface- and depth-recorded tooth pulp-evoked potentials had recovery functions that were covariant with rates of stimulation. In addition, stimulation of putative generator sites along the trigeminal lemniscal system reproduced portions of the tooth pulp-evoked surface-recorded potentials. Selective ablation of trigeminal cortical area 3 abolished ENFPs and lesions of lemniscal brain stem sites abolished FFPs . Disruption of extralemniscal brain stem sites had no effect on the surface-recorded evoked potentials examined. These findings and other supporting evidence from previous studies imply that the projection of fast-conducting tooth pulp input to the cortex may subserve a nonnociceptive modality and participate in sensorimotor integration.


Scalable Production of Recombinant Membrane Active Peptides and Its Potential as a Complementary Adjunct to Conventional Chemotherapeutics.
The production of short anticancer peptides in recombinant form is an alternative method for costly chemical manufacturing. However, the limitations of host toxicity, bioactivity and column purification have impaired production in mass quantities. In this study, short cationic peptides were produced in aggregated inclusion bodies by double fusion with a central protein that has anti-cancer activity. The anticancer peptides Tachiplicin I (TACH) and Latarcin 1 (LATA) were fused with the N- and C-terminus of the MAP30 protein, respectively. We successfully produced the recombinant TACH-MAP30-LATA protein and MAP30 alone in E. coli that represented 59% and 68% of the inclusion bodies. The purified form of the inclusion bodies was prepared by eliminating host cell proteins through multiple washing steps and semi-solubilization in alkaline buffer. The purified active protein was recovered by inclusive solubilization at pH 12.5 in the presence of 2 M urea and refolded in alkaline buffer containing oxides and reduced glutathione. The peptide-fusion protein showed lower CC50 values against cancer cells (HepG2, 0.35±0.1 μM and MCF-7, 0.58±0.1 μM) compared with normal cells (WRL68, 1.83±0.2 μM and ARPE19, 2.5±0.1 μM) with outstanding activity compared with its individual components. The presence of the short peptides facilitated the entry of the peptide fusion protein into cancer cells (1.8 to 2.2-fold) compared with MAP30 alone through direct interaction with the cell membrane. The cancer chemotherapy agent doxorubicin showed higher efficiency and selectivity against cancer cells in combination with the peptide- fusion protein. This study provides new data on the mass production of short anticancer peptides as inclusion bodies in E. coli by fusion with a central protein that has similar activity. The product was biologically active against cancer cells compared with normal cells and enhanced the activity and selective delivery of an anticancer chemotherapy agent.


Interaction proteomics of synapse protein complexes.
The brain integrates complex types of information, and executes a wide range of physiological and behavioral processes. Trillions of tiny organelles, the synapses, are central to neuronal communication and information processing in the brain. Synaptic transmission involves an intricate network of synaptic proteins that forms the molecular machinery underlying transmitter release, activation, and modulation of transmitter receptors and signal transduction cascades. These processes are dynamically regulated and underlie neuroplasticity, crucial to learning and memory formation. In recent years, interaction proteomics has increasingly been used to elucidate the constituents of synaptic protein complexes. Unlike classic hypothesis-based assays, interaction proteomics detects both known and novel interactors without bias. In this trend article, we focus on the technical aspects of recent proteomics to identify synapse protein complexes, and the complementary methods used to verify the protein-protein interaction. Moreover, we discuss the experimental feasibility of performing global analysis of the synapse protein interactome.


Determination of the initial exothermic reaction of shredded tyres with wire content.
This paper presents the cause of exothermic reactions in shredded tyre with exposed wire content in shredded tyre piles. Data indicate that the oxidation of exposed steel wires is the exothermic reaction in shredded tyre embankments. This would lead to spontaneous combustion. Reaction of the steel with the sulphur or the carbon black appears not to be the source of the exothermic. Laboratory tests have been conducted to determine the heat transfer properties of the materials that compose tyres (i.e., tyre rubber and wires) by using a hot-plate apparatus. In addition, one-dimensional heat conduction experiments were conducted to compare the flow of heat through the materials while varying the physical and environmental conditions. The physical conditions were the size of tyre shred, water content, and wire contents. An exothermic reaction occurred when exposed wire was present but not when it was absent. A one-dimensional heat transfer equation was developed, and parametric studies were conducted to verify the laboratory model. Exothermic reaction was found to increase linearly with temperature, size and shape of the shredded tyres, density, amount of wire in shredded tyres, and water content.


Play as physical flexibility training in five ceboid primates.
Instantaneous focal animal sampling of positional behavior (posture and locomotion) during the play and nonplay of adults and juveniles of 5 ceboid monkeys (Alouatta palliata, Ateles geoffroyi, Cacajao calvus, Cebus capucinus, and Saimiri boliviensis) in an optimal design field study of the function of play as physical flexibility training produced a sample of 98,261 observations. Analyses of 67 distinct modes of positional behavior demonstrated that significantly enhanced rates of suspension and nonquadrupedal locomotion plus reduced rates of quadrupedal locomotion (especially quadrupedal walking) typified play in all 5 species. These findings support the hypothesis that play promotes the development of dynamic and static flexibility in arboreal primates. This argument from design that play functions as physical flexibility training was discussed as fully compatible with other functional interpretations.


Specialization and Injury Risk in Different Youth Sports: A Bio-Emotional Social Approach.
Sport specialization is an actual trend in youth athletes, but it can increase injury risk. The aim was to determine the eventual correlation between sports specialization and injury risk in various sports, using a biopsychosocial approach. 169 sport-specialized athletes completed [(38 female, 131 male); overall (11.2 ± 2.7 years), (56.28 ± 15.72 kg), (161.3 ± 15.52 cm)] a self-reported questionnaire regarding sociodemographic (age, gender, educational level), physical-attitudinal, injuries and psychological-attitudinal To analyze data univariate and correlate analyses were used. Of 169 athletes enrolled, 53% were single-sport specialized (reported participation in one sport and trained > 8 months/year). In team sports (100%, OR = 0.75; p = 0.022) a high risk of having to remain at rest for up to 1 month because of overuse was observed. Males who suffered direct trauma (70%; OR = 1.03; p = 0.006) in the team group (95%, OR = 0.09; p = 0.008) were more exposed to that type of injury, and also the type of specialization figured significantly (p = 0.047). In addition, interoceptive awareness correlates with injury (95%, 1.04, p = 0.01). This study shows that, even though young athletes seem to be at a high risk of becoming injured, early team sport specialization and a high performance level cannot be considered to be the only risk factors.


Results of xenogeneic I-RNA therapy in patients with metastatic renal cell carcinoma.
Six patients with metastatic renal cell carcinoma were treated with five intravenous infusions (every other day) of autologous lymphocytes incubated in vitro with I-RNA extracted from the lymphoid tissue of guinea pigs immunized with the patient's own tumor. No toxicity was evident. One patient showed regression of multiple pulmonary metastases beginning three months after therapy with complete remission by six months. She remained without evidence of disease until 18 months after therapy. Two other patients had more than 50% regression of measurable metastases lasting eight and ten months after therapy. Two patients showed stabilization of previously growing renal cell carcinoma pulmonary metastases. A single patient with renal cell carcinoma metastatic to brain had progressive tumor growth after a single I-RNA treatment. Serial peripheral blood lymphocyte samples obtained from each of the patients during I-RNA therapy demonstrated progressive increase in in vitro cytolysis of allogeneic renal cell carcinoma targets. Boosts in cytolytic effect were shown in all patients during I-RNA treatment regardless of their subsequent clinical course. These results seem to justify a randomized, prospective trial of xenogeneic I-RNA therapy in renal cell carcinoma patients with lesser tumor burden.


Hybrid Antifouling and Antimicrobial Coatings Prepared by Electroless Co-Deposition of Fluoropolymer and Cationic Silica Nanoparticles on Stainless Steel: Efficacy against Listeria monocytogenes.
Controlling formation, establishment, and proliferation of microbial biofilms on surfaces is critical for ensuring public safety. Herein, we report on the synthesis of antimicrobial nanoparticles and their co-deposition along with fluorinated nanoparticles during electroless nickel plating of stainless steel. Plating bath composition is optimized to ensure sufficiently low surface energy to resist fouling and microbial adhesion as well as to exert significant (>99.99% reduction) antimicrobial activity against Listeria monocytogenes. The resulting coatings present hybrid antifouling and antimicrobial character, can be applied onto stainless steel, and do not rely on leaching or migration of the antimicrobial nanoparticles to be effective. Such coatings can support reducing public health issues related to microbial cross-contamination in areas such as food processing, hospitals, and water purification.


The metal-responsive transcription factor-1 contributes to HIF-1 activation during hypoxic stress.
Hypoxia-inducible factor-1 (HIF-1), the major transcriptional regulator of the mammalian cellular response to low oxygen (hypoxia), is embedded within a complex network of signaling pathways. We have been investigating the importance of another stress-responsive transcription factor, MTF-1, for the adaptation of cells to hypoxia. This article reports that MTF-1 plays a central role in hypoxic cells by contributing to HIF-1 activity. Loss of MTF-1 in transformed Mtf1 null mouse embryonic fibroblasts (MEFs) results in an attenuation of nuclear HIF-1alpha protein accumulation, HIF-1 transcriptional activity, and expression of an established HIF-1 target gene, glucose transporter-1 (Glut1). Mtf1 null (Mtf1 KO) MEFs also have constitutively higher levels of both glutathione (GSH) and the rate-limiting enzyme involved in GSH synthesis--glutamate cysteine ligase catalytic subunit--than wild type cells. The altered cellular redox state arising from increased GSH may perturb oxygen-sensing mechanisms in hypoxic Mtf1 KO cells and decrease the accumulation of HIF-1alpha protein. Together, these novel findings define a role for MTF-1 in the regulation of HIF-1 activity.


A non-destructive virtual dissection by micro-CT reveals diagnostic characters in the type specimen of Caloptilia stigmatella (Lepidoptera: Gracillariidae).
Nearly a century ago, wing venation was introduced in gracillariid taxonomy as a means to diagnose closely related genera and species groups. Recent advances in non-destructive virtual micro-dissections suggest promising approaches with which to revisit the relevance of wing venation characters on historic primary type specimens. Many unique type specimens in Gracillariidae and other microlepidoptera groups preserved in museum collections are in poor condition, and over the course of history have suffered loss or damage to their abdomens. Consequently, genitalia morphology is not available for diagnoses and comparisons. In this paper we emphasize the need to include the type species and type specimens into the broader context of taxonomic studies on micro-moths in general and the family Gracillariidae in particular. The genus Caloptilia has a world-wide distribution and has been the subject of research for more than 200 years, yet the generic boundaries and groupings within the genus are still unresolved due to the lack of a reliable set of taxonomic characters obtained from the primary types. We describe a method of virtual descaling of the fore- and hindwings using the unset micro-moth type specimen of Caloptilia stigmatella Fabricius, 1781, in order to demonstrate that the study of historic and fragile type specimens and diagnoses of their internal morphological characters becomes possible by applying new and non-destructive technology.


Effect of topiramate on choroidal thickness and anterior chamber parameters in the treatment of patients with migraine.
To investigate the effects of topiramate on choroidal thickness and anterior chamber parameters using optical coherence tomography in the treatment of patients with migraine. A total of 22 eyes of 22 adults (12 females, 10 males) diagnosed with migraine and scheduled to topiramate treatment for pain control were recruited in this prospective study. Choroidal thickness (CT), anterior chamber depth (ACD), anterior chamber angle (ACA), spherical refractive equivalent (SphEq) and intraocular pressure (IOP) measurements were recorded at baseline (prior the topiramate therapy), first and second month visits for the statistical analysis. One-way ANOVA with repeated measures test was used for the statistical evaluation. Mean age of the patients was 40.2 ± 6.5 years. Mean CT at central fovea was 324 ± 47 μm initially, 341 ± 45 μm in the first month and 344 ± 46 μm in the second month, thus first and second month measures were significantly higher than base values (p < 0.001). There was also a slight increase in IOP values among baseline (15.5 ± 2.4 mmHg) and follow-up visits (17.5 ± 2.6 mmHg, 19.0 ± 3.3 mmHg, respectively, ` p = 0.001). Baseline ACD (3.66 ± 0.22 mm) measures significantly decreased at the first month (3.63 ± 0.22 mm) and second month (3.62 ± 0.22 mm, p = 0.009). Also, a significant reduction was detected in the first (36.2 ± 4.9°) and second month (35.9 ± 5.1°) ACA measures comparing with baseline (39.1 ± 5.1°, p = 0.05). A significant myopic shift was determined in the first and second month SphEq values (-0.08 ± 0.6, -0.10 ± 0.6, respectively, p = 0.05). The study revealed increased CT and altered anterior chamber parameters and IOP due to topiramate therapy. Therefore, the patients using topiramate should be carefully monitored by an ophthalmologist considering the possible side effects.


Dietary Fiber Intake and Femoral Bone Mineral Density in Middle-Aged and Older US Adults: A Cross-Sectional Study of National Health and Nutrition Examination Survey 2013-2014.
Sufficient dietary fiber intake (DFI) is considered necessary for human health. However, the association between DFI and bone mineral density (BMD) remains unclear. Therefore, this study aimed to investigate the association between DFI and BMD and to determine whether sex modifies the association between DFI and BMD. Participants aged ≥ 40 years from the 2013-2014 National Health and Nutrition Examination Survey were included in the final analysis. The association between DFI and BMD was evaluated using a multivariate linear regression model. The non-linear relationship between DFI and BMD was characterized by smooth curve fittings and generalized additive models. Finally, 1,935 participants with a mean age of 58.12 ± 11.84 years were included in the final analysis. The results revealed that DFI was positively associated with femoral BMD in the unadjusted model. However, no correlation was observed between DFI and femoral BMD after adjusting for covariates. Moreover, the results showed an inverted U-shaped association between total DFI and femoral BMD among men but not women for the nonlinear relationship between DFI and femoral BMD. In conclusion, our results indicate that DFI might not follow a linear relationship with femoral BMD, and sex factors might modify the association between DFI and BMD. Particularly, high total DFI might contribute to lower femoral neck BMD. However, more studies are needed to investigate whether the negative effect of high DFI on femoral BMD does exist and whether high DFI has clear biological effects on bone metabolism, such as increasing the risk of osteoporosis.


Determination of 4-nitrophenol in water by use of a screen-printed carbon electrode modified with chitosan-crafted ZnO nanoneedles.
The toxicity and environmental pollution by nitro aromatic compounds in water samples is the most recognized problem in worldwide. Hence, we have developed a simple and highly sensitive electrochemical method for the determination of 4-nitrophenol (4-NP) in water samples based on a chitosan (CHT) crafted zinc oxide nanoneedles (ZnO NDs) modified screen printed carbon electrode. The CHT/ZnO NDs were characterized by Field emission scanning electron microscope, Fourier transform infrared spectroscopy and X-ray diffraction technique. The CHT/ZnO NDs modified electrode showed an enhanced electrocatalytic activity and lower potential detection towards 4-NP, compared with other modified electrodes. Under optimum conditions, the differential pulse voltammetry (DPV) response of CHT/ZnO NDs modified electrode displayed a wide linear response range from 0.5 to 400.6μM towards the detection of 4-NP with a detection limit (LOD) of 0.23μM. The CHT/ZnO NDs modified electrode was used for specific and sensitive detection of 4-NP in presence of possible interfering species and common metal ions with long-term stability. In addition, the excellent analytical performance of the proposed sensor was successfully applied for determination of 4-NP in water samples.


Economic Inequalities in Latin America at the Base of Adverse Health Indicators.
There is increasing evidence supporting the existence of a link between income inequalities and health outcomes. The main purpose of this article is to test whether economic inequalities are associated with poor population health in Latin American countries. Multi-country data from 1970 to 2012 were used to assess this question. The results show that the Gini coefficient has a strong correlation with health outcomes. Moreover, multiple linear regression analysis using fixed effects shows that after controlling for gross national income per capita, literacy rate, and health expenditure, the Gini coefficient is independently negatively associated with health outcomes. In Latin American countries, for every percentage point increase in the Gini coefficient, the infant mortality rate grows by 0.467 deaths per 1,000 live births, holding all other variables constant. Additionally, an ordinary least squares estimation model suggests that countries that do not use International Monetary Fund loans perform better on health outcomes. These findings should alert policymakers, elected officials, and the public of the need to fight income inequalities and rethink the role of international financial institutions that dictate state policies.


Combination of lenalidomide and low-dose dexamethasone therapy promotes the anticoagulant activity of warfarin in patients with immunoglobulin light-chain amyloidosis.
The present study aimed to evaluate the drug interactions between warfarin and combination chemotherapy with lenalidomide and low-dose dexamethasone in immunoglobulin light-chain (AL) amyloidosis patients with unstable international normalized ratios (INR). The changes to INR values over time in 3 AL amyloidosis patients treated with warfarin and a combination of lenalidomide and low-dose dexamethasone between March 2011 and February 2015 were analyzed retrospectively. The mean INR value was 1.52 prior to the combination chemotherapy, and the value increased 1.7-fold during treatment. The median time to reach maximum values was 17 days. Horn's drug Interaction Probability Scale indicated a possible interaction between lenalidomide and warfarin. These patients exhibited no marked alterations in hepatic function or serum albumin concentrations prior to and following combination chemotherapy and no additional administration of CYP2C9 inhibitors or vitamin K supplements was conducted. In addition, no patient experienced chemotherapy-induced nausea or appetite loss. These findings suggest that the total clearance or protein binding of warfarin remained unchanged. Therefore, the combination of warfarin and lenalidomide may cause a pharmacodynamic interaction, more likely by inhibiting the production of interleukin-6. In conclusion, clinically important interactions between warfarin and lenalidomide and low-dose dexamethasone therapy were observed in AL amyloidosis patients, where INR values signi ficantly increased. Therefore, close and regular monitoring of patients during the course of treatment is important, and the dose of warfarin should be reduced if required.


Sustained (S)-roscovitine delivery promotes neuroprotection associated with functional recovery and decrease in brain edema in a randomized blind focal cerebral ischemia study.
Stroke is a devastating disorder that significantly contributes to death, disability and healthcare costs. In ischemic stroke, the only current acute therapy is recanalization, but the narrow therapeutic window less than 6 h limits its application. The current challenge is to prevent late cell death, with concomitant therapy targeting the ischemic cascade to widen the therapeutic window. Among potential neuroprotective drugs, cyclin-dependent kinase inhibitors such as (S)-roscovitine are of particular relevance. We previously showed that (S)-roscovitine crossed the blood-brain barrier and was neuroprotective in a dose-dependent manner in two models of middle cerebral artery occlusion (MCAo). According to the Stroke Therapy Academic Industry Roundtable guidelines, the pharmacokinetics of (S)-roscovitine and the optimal mode of delivery and therapeutic dose in rats were investigated. Combination of intravenous (IV) and continuous sub-cutaneous (SC) infusion led to early and sustained delivery of (S)-roscovitine. Furthermore, in a randomized blind study on a transient MCAo rat model, we showed that this mode of delivery reduced both infarct and edema volume and was beneficial to neurological outcome. Within the framework of preclinical studies for stroke therapy development, we here provide data to improve translation of pre-clinical studies into successful clinical human trials.


Surgical treatment of cervical spondylotic myelopathy complicating athetoid cerebral palsy.
Operative treatment was performed in nine patients with cervical spondylotic myelopathy complicating athetoid cerebral palsy. The first two patients were treated by laminectomy, and the other seven by anterior interbody fusion. The symptoms in both the laminectomy patients improved after operation, but became worse again when cervical instability developed; they then had to have an anterior fusion in addition. In six of the seven patients who had primary anterior fusion a halo-cast (or a halo-vest) was used to keep the cervical spine immobile, and good bony fusion was obtained with satisfactory results. However, in one patient no halo apparatus was used, bony union did not occur and the radiculopathy reappeared. In cervical myelopathy complicating athetoid cerebral palsy laminectomy is contra-indicated; anterior fusion combined with a halo apparatus is, however, satisfactory.


Multicluster oscillation death and chimeralike states in globally coupled Josephson Junctions.
We observe the multiclustered oscillation death and chimeralike states in an array of Josephson junctions under a combination of self-repulsive and cross-attractive mean-field interaction when each isolated junction is in a bistable state, a coexisting fixed point and an oscillatory state. We locate the parameter landscape of the multiclustered oscillation death and chimeralike states. Alternatively, a purely repulsive mean-field interaction in an array of all oscillatory junctions produces chimeralike states with signatures of metastability in the incoherent subpopulation of junctions.


2'-(2,3-Dihydroxybenzoyloxy)-7-ketologanin: a novel iridoid glucoside from the leaves of Gentiana kurroo.
A new bitter acylated iridoid glucoside, 2'-(2,3-dihydroxybenzoyloxy)-7-ketologanin (1), has been isolated from the leaves of Gentiana kurroo. The structure of the compound was elucidated conclusively by chemical analysis, and extensive 1D and 2D NMR experiments.


[Guidelines for the prevention and treatment of atherosclerosis and cardiovasculer diseases: treatment of diabetes mellitus, dyslipidemia and the prevention of stroke].
Atherosclerosis is one of the principal causes of morbidity and mortality worldwide. The recent decades have witnessed great advances both in the identification of risk factors for the development of atherosclerosis and the treatment of its complications. This effort was rewarded with the reduction of mortality rates from cardiovascular diseases. The need for an update of the recommendations for the prevention of atherosclerosis and cardiovascular diseases stems from a large body of recently published trials, leading to fundamental changes in the way we treat patients with various levels of risk. The second part of the guidelines deals with the treatment of diabetes mellitus, dyslipidemia and the prevention of stroke.


Link between stimulus otoacoustic emissions fine structure peaks and standing wave resonances in a cochlear model.
In response to an external stimulus, the cochlea emits sounds, called stimulus frequency otoacoustic emissions (SFOAEs), at the stimulus frequency. In this article, a three-dimensional computational model of the gerbil cochlea is used to simulate SFOAEs and clarify their generation mechanisms and characteristics. This model includes electromechanical feedback from outer hair cells (OHCs) and cochlear roughness due to spatially random inhomogeneities in the OHC properties. As in the experiments, SFOAE simulations are characterized by a quasiperiodic fine structure and a fast varying phase. Increasing the sound pressure level broadens the peaks and decreases the phase-gradient delay of SFOAEs. A state-space formulation of the model provides a theoretical framework to analyze the link between the fine structure and global modes of the cochlea, which arise as a result of standing wave resonances. The SFOAE fine structure peaks correspond to weakly damped resonant modes because they are observed at the frequencies of nearly unstable modes of the model. Variations of the model parameters that affect the reflection mechanism show that the magnitude and sharpness of the tuning of these peaks are correlated with the modal damping ratio of the nearly unstable modes. The analysis of the model predictions demonstrates that SFOAEs originate from the peak of the traveling wave.


Palliative care nursing for patients with neurological diseases: what makes the difference?
Neurodegenerative diseases progress slowly, creating increasing physical disability with unpredictable disease trajectories. The disease's life-threatening nature often places these patients in palliative care. There are several factors that complicate the care of patients with neurodegenerative diseases in palliative care units. Owing to physical impairments, there are many communication barriers between patients and staff. Nurses are not able to duplicate the patient's meticulous daily routine leading to caregiver mistrust in the nurse's competencies. Even if the patient is hospitalised, caregivers may not take the much-needed time off to recuperate. The placement of patients with neurodegenerative diseases in palliative care is confusing, since they rarely die during in-hospital treatment but might even get better due to multidisciplinary treatment. Finally, patients and caregivers lack adequate knowledge about disease progression and available help and support programmes. Patients with neurodegenerative diseases urgently need palliative care and nurses and caregivers need better preparation to appropriately deal with these diseases.


Evidence for a circadian rhythm of susceptibility to retinal light damage.
This study investigated a possible circadian rhythm of light damage susceptibility in photoreceptors of both cyclic light-reared and dark-reared rats. A single exposure to intense green light was administered, beginning either in the early light period, the late light period or the dark period. In some animals exposed in the dark period, the synthetic antioxidant dimethylthiourea was administered before or after the onset of intense light exposure. Retinas were examined either immediately after exposure or after 2 weeks of recovery in darkness. Rod outer segment length and outer nuclear layer thickness measurements were used to assess light damage, along with qualitative analysis of swelling and disruption of the outer retinal layers. In all animals, retinal light damage was the most severe when intense light exposure began during the dark period. However, this severe damage was significantly reduced by pretreatment with the antioxidant. In a separate set of unexposed animals, fluctuations in plasma adrenocorticotropic hormone (ACTH) and corticosterone concentrations followed the same time course, regardless of the light regime during rearing. Our data support the notion of a circadian rhythm of light damage susceptibility that peaks in the dark period and yet can be modulated by the exogenous administration of an antioxidant.


Strand specificity for UV-induced DNA repair and mutations in the Chinese hamster HPRT gene.
DNA excision repair modulates the mutagenic effect of many genotoxic agents. The recently observed strand specificity for removal of UV-induced cyclobutane dimers from actively transcribed genes in mammalian cells could influence the nature and distribution of mutations in a particular gene. To investigate this, we have analyzed UV-induced DNA repair and mutagenesis in the same gene, i.e. the hypoxanthine phosphoribosyl-transferase (hprt) gene. In 23 hprt mutants from V79 Chinese hamster cells induced by 2 J/m2 UV we found a strong strand bias for mutation induction: assuming that pre-mutagenic lesions occur at dipyrimidine sequences, 85% of the mutations could be attributed to lesions in the nontranscribed strand. Analysis of DNA repair in the hprt gene revealed that more than 90% of the cyclobutane dimers were removed from the transcribed strand within 8 hours after irradiation with 10 J/m2 UV, whereas virtually no dimer removal could be detected from the nontranscribed strand even up to 24 hr after UV. These data present the first proof that strand specific repair of DNA lesions in an expressed mammalian gene is associated with a strand specificity for mutation induction.


Synthesis and biological evaluation of 2-phenylpyran-4-ones: a new class of orally active cyclooxygenase-2 inhibitors.
A series of 2-phenylpyran-4-ones were prepared and evaluated for their ability to inhibit cyclooxygenase-2 (COX-2). Extensive structure-activity relationship work was carried out within this series, and a number of potent and selective COX-2 inhibitors were identified. Compounds having a p-methylsulfone group at the 2-phenyl ring showed the best COX-2 inhibitory activity. The introduction of a substituted phenoxy ring at position 3 enhanced both the in vitro and in vivo activity within the series. A selected group of 3-phenoxypyran-4-ones exhibited excellent activity in an experimental model of pyresis. The in vivo antiinflammatory activity of these compounds was confirmed with the evaluation of their antiarthritic and analgesic effectiveness. Moreover, their pharmacokinetic profile in rats is compatible with a once a day administration by oral route in humans. Within this novel series, compounds 21, 31, 34, and 35 have been selected for further preclinical and clinical evaluation.


Effect of short-chain organic acids on macromolecular synthesis in Escherichia coli.
Incubating cultures of Escherichia coli with propionic acid (5 mmol/l) or formic acid (10 mmol/l) at pH 5.0 produced bacteriostasis lasting 30 and 120 min respectively. During this time rates of RNA, DNA, protein, lipid and cell wall synthesis were reduced. Growth resumed after continued incubation in the presence of acid, but cells from acid-treated cultures were larger than controls. DNA synthesis was particularly sensitive to the presence of the propionic or formic acid.


Effect of Precursor Stoichiometry on the Performance and Stability of MAPbBr3 Photovoltaic Devices.
The wide-bandgap methylammonium lead bromide perovskite is promising for applications in tandem solar cells and light-emitting diodes. Despite its utility, there is a limited understanding of its reproducibility and stability. Herein, the dependence of the properties, performance, and shelf storage of thin films and devices on minute changes to the precursor solution stoichiometry is examined in detail. Although photovoltaic cells based on these solution changes exhibit similar initial performance, shelf storage depends strongly on precursor solution stoichiometry. While all devices exhibit some degree of healing, bromide-deficient films show a remarkable improvement, more than doubling in their photoconversion efficiency. Photoluminescence spectroscopy experiments performed under different atmospheres suggest that this increase is due, in part, to a trap-healing mechanism that occurs upon exposure to the environment. The results highlight the importance of understanding and manipulating defects in lead halide perovskites to produce long-lasting, stable devices.


A neural mechanism of the relationship between impulsivity and emotion dysregulation in patients with Internet gaming disorder.
Impulsivity and emotion dysregulation have been known to be risk factors for Internet gaming disorder (IGD), but their underlying neural mechanisms are not yet fully understood. Given that the prefrontal cortex has a key role in higher order cognition and addiction, the present study aimed to investigate emotional influences on response inhibition in situations with different cognitive demands. A total of 41 young male adults (20 with and 21 without IGD) were scanned while performing two versions of an emotional go/no-go task with demands on low and high working memory load. Patients with IGD showed a failure in response inhibition and increased activation of widespread brain regions, including prefrontal, motor-sensory, parietal, occipital, insula, and striatal regions across tasks. Among these regions, involvement of the dorsolateral prefrontal cortex and ventral striatum was observed only during the task with high demands on working memory. Moreover, it was also only during the high-load task that interaction between response inhibition and emotional states was observed in the dorsomedial prefrontal cortex, with observations revealing that its alteration in patients with IGD was associated with number of hours spent on Internet gaming. Our findings highlight a failure of response inhibition and dysfunction within the inhibitory control network. The special significance of our study is that dysfunctional dorsomedial prefrontal cortex may mediate abnormal emotional influences on response inhibition in patients with IGD.


Long noncoding RNA hypoxia-inducible factor 1 alpha-antisense RNA 1 promotes tumor necrosis factor-α-induced apoptosis through caspase 3 in Kupffer cells.
Kupffer cells (KCs) play a crucial role in the pathogenesis of acute-on-chronic liver failure (ACLF) which is characterized by acute and severe disease in patients with preexisting liver disease and shows high mortality. Long noncoding RNAs (lncRNAs) are recently found to be involved in gene regulation. However, the mechanisms of how KCs are regulated by inflammatory factors, tumor necrosis factor-α (TNF-α), and whether lncRNAs are involved in the process remain largely unknown. Hence, we investigated the role of lncRNAs in the cytotoxicity of TNF-α on KCs.lncRNA array (The lncRNAs in the array are apoptosis-related lncRNAs reported in some research papers.) was used to identify lncRNAs related with liver fibrosis. Annexin V/protease inhibitor (PI) staining was used for detection of cell apoptosis. Real time-polymerase chain reaction was utilized for analysis of mRNA levels of lncRNA hypoxia-inducible factor 1 alpha-antisense RNA 1 (HIF1A-AS1) and apoptosis-related genes. Western blot was implied to the determination of lymphoid enhancer factor-1 (LEF-1).In this study, we found that HIF1A-AS1 could be upregulated by TNF-α by lncRNA array analysis and knockdown of HIF1A-AS1 significantly rescued cell apoptosis induced by TNF-α. Moreover, inhibition of HIF1A-AS1 markedly reduced mRNA level of caspase 3 which can be significantly enhanced by TNF-α. Furthermore, HIF1A-AS1 showed binding sites for LEF-1 and siRNA-mediated downregulation of LEF-1 decreased HIF1A-AS1 level in KCs treated with TNF-α.This study elucidates a new role of HIF1A-AS1 in TNF-α-induced cell apoptosis and provides potential therapeutic targets for ACLF.


Autocatalytic amplification of Alzheimer-associated Aβ42 peptide aggregation in human cerebrospinal fluid.
Alzheimer's disease is linked to amyloid β (Aβ) peptide aggregation in the brain, and a detailed understanding of the molecular mechanism of Aβ aggregation may lead to improved diagnostics and therapeutics. While previous studies have been performed in pure buffer, we approach the mechanism in vivo using cerebrospinal fluid (CSF). We investigated the aggregation mechanism of Aβ42 in human CSF through kinetic experiments at several Aβ42 monomer concentrations (0.8-10 µM). The data were subjected to global kinetic analysis and found consistent with an aggregation mechanism involving secondary nucleation of monomers on the fibril surface. A mechanism only including primary nucleation was ruled out. We find that the aggregation process is composed of the same microscopic steps in CSF as in pure buffer, but the rate constant of secondary nucleation is decreased. Most importantly, the autocatalytic amplification of aggregate number through catalysis on the fibril surface is prevalent also in CSF.


Chitosans for delivery of nucleic acids.
Alternatives to efficient viral vectors in gene therapy are desired because of their poor safety profiles. Chitosan is a promising non-viral nucleotide delivery vector because of its biocompatibility, biodegradability, low immunogenicity and ease of manufacturing. Since the transfection efficiency of chitosan polyplexes is relatively low compared to viral counterparts, there is an impetus to gain a better understanding of the structure-performance relationship. Recent progress in preparation and characterisation has enabled coupling analysis of chitosans structural parameters that has led to increased TE by tailoring of chitosan's structure. In this review, we summarize the recent advances that have lead to a more rational design of chitosan polyplexes. We present an integrated review of all major areas of chitosan-based transfection, including preparation, chitosan and polyplexes physicochemical characterisation, in vitro and in vivo assessment. In each, we present the obstacles to efficient transfection and the strategies adopted over time to surmount these impediments.


Investigation of Optimum Mg Doping Content and Annealing Parameters of Cu2MgxZn1-xSnS4 Thin Films for Solar Cells.
Cu2MgxZn1-xSnS4 (0 ≤ x ≤0.6) thin films were prepared by a simple, low-temperature (300 °C) and low-cost sol-gel spin coating method followed by post-annealing at optimum conditions. We optimized the annealing conditions and investigated the effect of Mg content on the crystalline quality, electrical and optical performances of the Cu2MgxZn1-xSnS4 thin films. It was found that the Cu2MgxZn1-xSnS4 film annealed at 580 °C for 60 min contained large grain, less grain boundaries and high carrier concentration. Pure phase kesterite Cu2MgxZn1-xSnS4 (0 ≤ x ≤ 0.6) thin films were obtained by using optimal annealing conditions; notably, the smaller Zn2+ ions in the Cu2ZnSnS4 lattice were replaced by larger Mg2+ ions. With an increase in x from 0 to 0.6, the band gap energy of the films decreased from 1.43 to 1.29 eV. When the ratio of Mg/Mg + Zn is 0.2 (x = 0.2), the grain size of Cu2MgxZn1-xSnS4 reaches a maximum value of 1.5 μm and the surface morphology is smooth and dense. Simultaneously, the electrical performance of Cu2MgxZn1-xSnS4 thin film is optimized at x = 0.2, the carrier concentration reaches a maximum value of 3.29 × 1018 cm-3.


Randomized clinical trials of cancer treatment--a public opinion survey.
An interview survey was carried out among 1022 adults, representative of a cross-section of the population aged 16-70, to find out how people reacted to the idea of participating in randomized clinical trials of cancer treatment. A secondary purpose of the survey was to learn whether or not people wanted their doctor to give them information about their illness, the treatment and the trials. Overall, there was no evidence of antipathy to the concept of randomized trials. Two out of three of those interviewed were prepared to participate, except in the most demanding situations when just over half wished to choose their own treatment. There was a strong response in favour of being given information and a very high level of confidence in doctors. Both respondents and interviewers were enthusiastic about participating in the survey.


Differential connectivity of gene regulatory networks distinguishes corticosteroid response in asthma.
Variations in drug response between individuals have prevented us from achieving high drug efficacy in treating many complex diseases, including asthma. Genetics plays an important role in accounting for such interindividual variations in drug response. However, systematic approaches for addressing how genetic factors and their regulators determine variations in drug response in asthma treatment are lacking. We sought to identify key transcriptional regulators of corticosteroid response in asthma using a novel systems biology approach. We used Passing Attributes between Networks for Data Assimilations (PANDA) to construct the gene regulatory networks associated with good responders and poor responders to inhaled corticosteroids based on a subset of 145 white children with asthma who participated in the Childhood Asthma Management Cohort. PANDA uses gene expression profiles and published relationships among genes, transcription factors (TFs), and proteins to construct the directed networks of TFs and genes. We assessed the differential connectivity between the gene regulatory network of good responders versus that of poor responders. When compared with poor responders, the network of good responders has differential connectivity and distinct ontologies (eg, proapoptosis enriched in network of good responders and antiapoptosis enriched in network of poor responders). Many of the key hubs identified in conjunction with clinical response are also cellular response hubs. Functional validation demonstrated abrogation of differences in corticosteroid-treated cell viability following siRNA knockdown of 2 TFs and differential downstream expression between good responders and poor responders. We have identified and validated multiple TFs influencing asthma treatment response. Our results show that differential connectivity analysis can provide new insights into the heterogeneity of drug treatment effects.


Functionalized Au22 clusters: synthesis, characterization, and patterning.
We synthesized fluorescent, porphyrin-anchored, Au(22) clusters in a single step, starting from well-characterized Au(25) clusters protected with glutathione (-SG) by a combined core reduction/ligand exchange protocol, at a liquid-liquid interface. The prepared cluster was characterized by UV/vis, photoluminescence, X-ray photoelectron spectroscopy (XPS), scanning electron microscopy, elemental analysis, and matrix-assisted laser desorption ionization mass spectrometry. The absence of a 672 nm intraband transition of Au(25) and the simultaneous emergence of new characteristic peaks at 520 and 635 nm indicate the formation of the Au(22) core. An increase in the binding energy of 0.4 eV in Au 4f core-level peaks confirmed the presence of a reduced core size. Quantitative XPS confirmed the Au/S ratio. The presence of a free base, tetraphenylporphyrin (H(2)TPPOAS-), on the Au(22) core was confirmed by fluorimetric titrations with Cu(2+) and Zn(2+) ions. From all of these, the composition of the cluster was determined to be Au(22)[(-SG)(15)(-SAOPPTH(2))(2)], which was supported by mass spectrometry and elemental analysis. We utilized the fluorescence nature of these water-soluble clusters for the fabrication of fluorescent patterns by soft lithography. The patterns were studied using tapping-mode atomic force microscopy and confocal fluorescence imaging.


Role of trunk muscles in generating follower load in the lumbar spine of neutral standing posture.
Recently, experimental results have demonstrated that the load carrying capacity of the human spine substantially increases under the follower load condition. Thus, it is essential to prove that a follower load can be generated in vivo by activating the appropriate muscles in order to demonstrate the possibility that the stability of the spinal column could be maintained through a follower load mechanism. The aim of this study was to analyze the coordination of the trunk muscles in order to understand the role of the muscles in generating the follower load. A three-dimensional finite element model of the lumbar spine was developed from T12 to S1 and 117 pairs of trunk muscles (58 pairs of superficial muscles and 59 pairs of deep muscles) were considered. The follower load concept was mathematically represented as an optimization problem. The muscle forces required to generate the follower load were predicted by solving the optimization problem. The corresponding displacements and rotations at all nodes were estimated along with the follower forces, shear forces, and joint moments acting on those nodes. In addition, the muscle forces and the corresponding responses were investigated when the activations of the deep muscles or the superficial muscles were restricted to 75% of the maximum activation, respectively. Significantly larger numbers of deep muscles were involved in the generation of the follower load than the number of superficial muscles, regardless of the restriction on muscle activation. The shear force and the resultant joint moment are more influenced by the change in muscle activation in the superficial muscles. A larger number of deep trunk muscles were activated in order to maintain the spinal posture in the lumbar spine. In addition, the deep muscles have a larger capability to reduce the shear force and the resultant joint moment with respect to the perturbation of the external load or muscle fatigue compared to the superficial muscles.


STI and HIV knowledge and testing: a comparison of domestic Australian-born, domestic overseas-born and international university students in Australia.
University students usually consist of young people from culturally and linguistically diverse backgrounds, and a group recognised as being at increased risk of STI. This study found lower levels of STI knowledge and STI testing among international students and to a lesser extent, domestic overseas-born students, compared with domestic Australian-born students. International students exhibited lower risk sexual behaviour but were more likely to have had a HIV test than domestic students. This diversity in sexual health knowledge, sexual health services utilisation and sexual experience indicates the need for a variety of public health approaches to improve sexual health.


Differential roles of ERα and ERβ in normal and neoplastic development in the mouse mammary gland.
The present experiments were performed to determine the roles of estrogen receptors α and β (ERα and ERβ) in normal and neoplastic development in the mouse mammary gland. In wild-type mice, in vivo administration of estradiol (E) + progesterone (P) stimulated mammary ductal growth and alveolar differentiation. Mammary glands from mice in which the ERβ gene has been deleted (βERKO mice) demonstrated normal ductal growth and differentiation in response to E + P. By contrast, mammary glands from mice in which the ERα gene has been deleted (αERKO mice) demonstrated only rudimentary ductal structures that did not differentiate in response to E + P. EGF demonstrates estrogen-like activity in the mammary glands of αERKO mice: treatment of αERKO mice with EGF + P (without E) supported normal mammary gland development, induced expression of progesterone receptor (PR), and increased levels of G-protein-coupled receptor (GPR30) protein. Mammary gland development in βERKO mice treated with EGF + P was comparable to that of wild-type mice receiving EGF + P; EGF had no statistically significant effects on the induction of PR or expression of GPR30 in mammary glands harvested from either wild-type mice or βERKO mice. In vitro exposure of mammary glands to 7,12-dimethylbenz[a]anthracene (DMBA) induced preneoplastic mammary alveolar lesions (MAL) in glands from wild-type mice and βERKO mice, but failed to induce MAL in mammary glands from αERKO mice. Microarray analysis of DMBA-treated mammary glands identified 28 functional pathways whose expression was significantly different in αERKO mice versus both βERKO and wild-type mice; key functions that were differentially expressed in αERKO mice included cell division, cell proliferation, and apoptosis. The data demonstrate distinct roles for ERα and ERβ in normal and neoplastic development in the mouse mammary gland, and suggest that EGF can mimic the ERα-mediated effects of E in this organ.


Second-line antiretroviral therapy in resource-limited settings: the experience of Médecins Sans Frontières.
To describe the use of second-line protease-inhibitor regimens in Médecins Sans Frontières HIV programmes, and determine switch rates, clinical outcomes, and factors associated with survival. We used patient data from 62 Médecins Sans Frontières programmes and included all antiretroviral therapy-naive adults (> 15 years) at the start of antiretroviral therapy and switched to a protease inhibitor-containing regimen with at least one nucleoside reverse transcriptase inhibitor change after more than 6 months of nonnucleoside reverse transcriptase inhibitor first-line use. Cumulative switch rates and survival curves were estimated using Kaplan-Meier methods, and mortality predictors were investigated using Poisson regression. Of 48,338 adults followed on antiretroviral therapy, 370 switched to a second-line regimen after a median of 20 months (switch rate 4.8/1000 person-years). Median CD4 cell count at switch was 99 cells/microl (interquartile ratio 39-200; n = 244). A lopinavir/ritonavir-based regimen was given to 51% of patients and nelfinavir-based regimen to 43%; 29% changed one nucleoside reverse transcriptase inhibitor and 71% changed two nucleoside reverse transcriptase inhibitors. Median follow-up on second-line antiretroviral therapy was 8 months, and probability of remaining in care at 12 months was 0.86. Median CD4 gains were 90 at 6 months and 135 at 12 months. Death rates were higher in patients in World Health Organization stage 4 at antiretroviral therapy initiation and in those with CD4 nadir count less than 50 cells/microl. The rate of switch to second-line treatment in antiretroviral therapy-naive adults on non-nucleoside reverse transcriptase inhibitor-based first-line antiretroviral therapy was relatively low, with good early outcomes observed in protease inhibitor-based second-line regimens. Severe immunosuppression was associated with increased mortality on second-line treatment.


The deformity correction and fixator-assisted treatment using Ilizarov versus Taylor spatial frame in the foot and ankle.
This study was to report the comparison of outcomes between Ilizarov ring fixator (IRF) and Taylor Spatial Frame® (Smith & Nephew, Memphis, Tenn.; TSF) in terms of the effectiveness of ankle-foot deformities correction, follow-up results, and complications. Fourteen patients with ankle-foot deformities were corrected using circular external fixation (IRF group = 7 patients; TSF group = 7 patients) and related procedures. Baseline data and treatment variables were recorded. The patients' mean age was 42.9 years. Mean follow-up time was 6.5 months. Most common cause of deformity/traumatic condition was posttraumatic equinus. There were successful results in 8 patients (57.1%), partial successful results in 5 patients (35.7%), and revision-needed in 1 patient (7.1%). TSF group demonstrated significantly higher rate of successful results than IRF group (P=0.033). A trend of lower complication rate was found in TSF group (P=0.286). Deformity corrections using TSF provided significantly better clinical scores and higher rate of successful outcome than conventional IRF.


Structure and transport mechanism of the sodium/proton antiporter MjNhaP1.
Sodium/proton antiporters are essential for sodium and pH homeostasis and play a major role in human health and disease. We determined the structures of the archaeal sodium/proton antiporter MjNhaP1 in two complementary states. The inward-open state was obtained by x-ray crystallography in the presence of sodium at pH 8, where the transporter is highly active. The outward-open state was obtained by electron crystallography without sodium at pH 4, where MjNhaP1 is inactive. Comparison of both structures reveals a 7° tilt of the 6 helix bundle. (22)Na(+) uptake measurements indicate non-cooperative transport with an activity maximum at pH 7.5. We conclude that binding of a Na(+) ion from the outside induces helix movements that close the extracellular cavity, open the cytoplasmic funnel, and result in a ∼5 Å vertical relocation of the ion binding site to release the substrate ion into the cytoplasm.


Mapping critical interactive sites within the periplasmic domain of the Vibrio cholerae type II secretion protein EpsM.
The type II secretion (T2S) system is present in many gram-negative species, both pathogenic and nonpathogenic, where it supports the delivery of a variety of toxins, proteases, and lipases into the extracellular environment. In Vibrio cholerae, the T2S apparatus is composed of 12 Eps proteins that assemble into a multiprotein complex that spans the entire cell envelope. Two of these proteins, EpsM and EpsL, are key components of the secretion machinery present in the inner membrane. In addition to likely forming homodimers, EpsL and EpsM have been shown to form a stable complex in the inner membrane and to protect each other from proteolytic degradation. To identify and map the specific regions of EpsM involved in protein-protein interactions with both another molecule of EpsM and EpsL, we tested the interactions of deletion constructs of EpsM with full-length EpsM and EpsL by functional characterization and copurification as well as coimmunoprecipitation. Analysis of the truncated EpsM mutants revealed that the region of EpsM from amino acids 100 to 135 is necessary for EpsM to form homo-oligomers, while residues 84 to 99 appear to be critical for a stable interaction with EpsL.


Expression and ontogeny of CD2 on murine B cells.
Expression of CD2 on developing and mature murine B cells was examined by using an antipeptide antiserum (L50). Most Ig-bearing splenic B cells were found to express CD2. Anti-CD5 and anti-B220 mAb divided the peritoneal B cells into two populations expressing high and low levels of these proteins; both populations were found to express uniform levels of CD2. Abelson murine leukemia virus-transformed pre-B cell lines derived from fetal liver and adult bone marrow were analyzed to delineate the ontogeny of CD2 in the B cell lineage. The results show that onset of CD2 expression correlates with the presence of cytoplasmic mu-chain. Therefore, the earliest CD2+ pre-B cell in the developing B cell population appears to be the classical pre-B cell.


Is there a bidirectional relationship between workplace bullying and the risk of sickness absence? Systematic review and meta-analysis of prospective studies.
Exposure to workplace bullying increases the risk of sickness absence. However, the extent and direction of this relationship for different follow-up lengths are not well established. To provide evidence regarding the direction and extent of the relationship between workplace bullying and different durations of sickness absence. We searched nine databases from their inception to 29 November 2022. Multiple independent observers screened the literature, extracted the data and used the Risk Of Bias In Non-randomised Studies of Exposure to assess the methodological quality. The overall effect sizes of odds ratio, relative risk, hazard ratio and 95% confidence intervals were calculated. Our meta-analysis demonstrated a 26% increased risk of sick leave among workers exposed to workplace bullying for all follow-up lengths (95% CI 1.18 to 1.35), even after adjusting for confounding factors. Moreover, we found a significant association between long-term sickness absence and a higher likelihood of subsequent exposure to workplace bullying, with a pooled OR of 1.63 (95% CI 1.21 to 2.04). Our study established a bidirectional relationship between workplace bullying and long-term sickness absence, highlighting that it increases the risk of sickness absence at different follow-up lengths among employees who have been bullied. Hence, organisations should be mindful of workers who resume work after prolonged absences due to illness and adopt appropriate management strategies to prevent workplace bullying.


The usefulness of serum human kallikrein 11 for discriminating between prostate cancer and benign prostatic hyperplasia.
Prostate-specific antigen (PSA) is the most useful tumor marker for diagnosis and monitoring of prostate cancer (CaP). Recently, we developed a specific immunoassay for human kallikrein 11 (hK11), one of the kallikrein gene family members, and found that hK11 was highly expressed in prostatic tissue and could be detected in seminal plasma (E. P. Diamandis et al., Cancer Res., 62: 295-300, 2002). The aim of this study was to investigate whether serum hK11 levels could be used to discriminate CaP from benign prostatic hyperplasia (BPH). We analyzed for hK11, total PSA, and percentage of free PSA, 150 serum samples from men with histologically confirmed BPH (n = 64) or CaP (n = 86). Total and free PSA levels were measured by the Immulite PSA assay, and hK11 levels were measured by our previously published immunofluorometric assay. Serum hK11 levels and the hK11:total PSA ratio were both significantly lower in CaP patients than in BPH patients. In the subgroup of patients with percentage of free PSA less than 20, an additional 54% of BPH patients could have avoided biopsies by using the hK11:total PSA ratio. Receiver operating characteristic (ROC) curve analysis demonstrated that the hK11:total PSA ratio [area under the curve (AUC), 0.83] and percentage of free PSA (AUC, 0.83) were much stronger predictors of CaP than total PSA (AUC, 0.69). These preliminary data suggest that the hK11:total PSA ratio could be a useful tumor marker for CaP and could be combined with percentage of PSA to further reduce the number of unnecessary prostatic biopsies.


Reaction time in psychomotor vigilance task is related to hypoxic load in males with sleep apnea.
Oxygen saturation (SpO2 )-based parameters are more strongly linked to impaired daytime vigilance than the conventional diagnostic metrics in patients with obstructive sleep apnea (OSA). However, whether the association between SpO2 -based parameters and impaired daytime vigilance is modulated by sex, remains unknown. Hence, we investigated the interplay between sex and detailed SpO2 -based metrics and their association with impaired vigilance in patients with OSA. The study population consisted of 855 (473 males, 382 females) patients with suspected OSA who underwent overnight polysomnography and psychomotor vigilance task (PVT). The population was grouped by sex and divided into quartiles (Q1-Q4) based on median reaction times (RTs) in the PVT. In addition to conventional diagnostic metrics, desaturation severity (DesSev), fall severity (FallSev), and recovery severity (RecovSev) were compared between the sexes and between the best (Q1) and worst (Q4) performing quartiles by using cumulative distribution functions (CDFs). Additionally, sex-specific covariate-adjusted linear regression models were used to investigate the connection between the parameters and RTs. The CDFs showed significantly higher hypoxic load in Q4 in males compared to females. In addition, the DesSev (β = 8.05, p < 0.01), FallSev (β = 6.48, p = 0.02), RecovSev (β = 9.13, p < 0.01), and Oxygen Desaturation Index (β = 12.29, p < 0.01) were associated with increased RTs only in males. Conversely, the Arousal Index (β = 10.75-11.04, p < 0.01) was associated with impaired vigilance in females. The severity of intermittent hypoxaemia was strongly associated with longer RTs in males whereas the Arousal Index had the strongest association in females. Thus, the impact of hypoxic load on impaired vigilance seems to be stronger in males than females.


How can collaboration be strengthened between public health and primary care? A Dutch multiple case study in seven neighbourhoods.
Although public health and primary care share the goal of promoting the health and wellbeing of the public, the two health sectors find it difficult to develop mutually integrated plans and to collaborate with each other. The aim of this multiple case study was to compare seven neighbourhoods in which a stepwise approach based on two central tools (district health profile and policy dialogue) was used to develop integrated district plans and promote collaboration. The stepwise approach involved the following steps: 1 Getting to know the neighbourhood, 2 Assembling the workgroup, 3 Analysing the neighbourhood, 4 Developing a district health profile, 5 Preparing policy dialogue, 6 Holding local dialogues, 7 Embedding integrated district plans and collaboration. To supervise this process, a core team was assembled for each neighbourhood, consisting of people drawn from both public health and primary care. Both the use of the two tools and the collaboration were studied by means of documentary analysis, interviews, questionnaires and observations. The seven neighbourhoods differed in the way the two tools of the stepwise approach were used: general versus focused profiles, the actors involved, the aims of the dialogue or the intensity of the steps. There were also similarities: profile indicators (e.g., population prognosis, vulnerability) and dialogue themes (e.g., obesity, social cohesion). The local actors experienced that the combination of both tools facilitates the process of bringing public health and primary care closer together, and that it is essential to invest sufficiently in the integration of profile data and in involving appropriate actors in the dialogue (e.g., GPs, residents). Collaboration was perceived as positive (e.g., feels involved, focus on consensus), but a starting process. Local actors also believe that the stepwise approach supported the process. A stepwise approach involving the combined use of district health profiles and policy dialogues promotes the integrated planning of health activities and facilitates collaboration between public health and primary care at the local level. Local differences may arise in the intensity and form of the various steps, but because they are practical and clearly defined, they remain transferrable to other neighbourhoods.


Customers' attributional judgments towards complaint handling in airline service: a confirmatory study based on attribution theory.
Besides flight safety, complaint handling plays a crucial role in airline service. Based upon Kelley's attribution theory, in the present study customers' attributions were examined under different conditions of complaint handling by the airlines. There were 531 passengers (216 women; ages 21 to 63 years, M = 41.5, SD = 11.1) with experiences of customer complaints who were recruited while awaiting boarding. Participants received one hypothetical scenario of three attributional conditions about complaint handling and then reported their attributional judgments. The findings indicated that the passengers were most likely to attribute the company's complaint handling to unconditional compliance when the airline company reacted to customer complaints under low distinctiveness, high consistency, and when consensus among the airlines was low. On the other hand, most passengers attributed the company's complaint handling to conditional compliance under the conditions in which distinctiveness, consistency, and consensus were all high. The results provide further insights into how different policies of complaint management affect customers' attributions. Future directions and managerial implications are also discussed.


Misdiagnosis of food-borne foreign bodies outside of the digestive tract on magnetic resonance imaging: Two case reports.
Patients with foreign bodies in the digestive tract are often encountered, but complete penetration of a foreign body through the gastrointestinal tract is rare, and the choice of imaging method is very important. Improper selection may lead to missed diagnosis or misdiagnosis. An 81-year-old man was diagnosed as having a liver malignancy after he took magnetic resonance imaging and positron emission tomography/computed tomography (CT) examinations. The pain improved after the patient accepted gamma knife treatment. However, he was admitted to our hospital 2 mo later due to fever and abdominal pain. This time, he received a contrast-enhanced CT scan, which showed fish-boon-like foreign bodies in the liver with peripheral abscess formation, then he went to the superior hospital for surgery. It lasted for more than 2 mo from the onset of the disease to the surgical treatment. A 43-year-old woman with a 1 mo history of a perianal mass with no obvious pain or discomfort was diagnosed as having an anal fistula with the formation of a local small abscess cavity. Clinical perianal abscess surgery was performed, and fish bone foreign body was found in perianal soft tissue during the operation. For patients with pain symptoms, the possibility of foreign body perforation should be considered. Magnetic resonance imaging is not comprehensive and that a plain computed tomography scan of the pain area is necessary.


Improving the fixation of an artificial intervertebral disc.
The fixation of an artificial intervertebral disc has been studied especially with respect to the dimensions, the convexity of the endplates and the size of the fixation elements. From literature and cadaveric vertebrae, the dimensions and shape of the lumbar vertebral endplates were determined and the dimensions of fixation ribs for the artificial intervertebral disc were calculated. To withstand shear forces and prevent dislocation, two sagittal ribs, each 3.5 mm in height and at least 20 mm in length and four transversal ribs, each 1.5 mm in height and with a total length of 60 mm are sufficient. A range of five different sagittal diameters was selected as sufficient for all patients. At least 72.6 % of the endplate of the vertebrae is covered. A convexity with a radius of 140 mm limits the gap to 0.62 mm.


Validity of the SMS, Phone, and medical staff Examination sports injury surveillance system for time-loss and medical attention injuries in sports.
The accurate measurement of sport exposure time and injury occurrence is key to effective injury prevention and management. Current measures are limited by their inability to identify all types of sport-related injury, narrow scope of injury information, or lack the perspective of the injured athlete. The aims of the study were to evaluate the proportion of injuries and the agreement between sport exposures reported by the SMS messaging and follow-up telephone part of the SMS, Phone, and medical staff Examination (SPEx) sports injury surveillance system when compared to measures obtained by trained on-field observers and medical staff (comparison method). We followed 24 elite adolescent handball players over 12 consecutive weeks. Eighty-six injury registrations were obtained by the SPEx and comparison methods. Of them, 35 injury registrations (41%) were captured by SPEx only, 10 injury registrations (12%) by the comparison method only, and 41 injury registrations (48%) by both methods. Weekly exposure time differences (95% limits of agreement) between SPEx and the comparison method ranged from -4.2 to 6.3 hours (training) and -1.5 to 1.0 hours (match) with systematic differences being 1.1 hours (95% CI 0.7 to 1.4) and -0.2 (95% CI -0.3 to -0.2), respectively. These results support the ability of the SPEx system to measure training and match exposures and injury occurrence among young athletes. High weekly response proportions (mean 83%) indicate that SMS messaging can be used for player measures of injury consequences beyond time-loss from sport. However, this needs to be further evaluated in large-scale studies.


Nitrogen-Mediated Interaction: A Walnut-Aphid-Parasitoid System.
The effects of plant quality on natural enemies are often overlooked in planning and executing biological control programs for insect pests in agriculture. Plant quality, however, could help to explain some of the observed variation in effectiveness of biological control, as it can indirectly influence natural enemy populations. In this study, we used the walnut aphid Chromaphis juglandicola (Kaltenbach) to address the effect of increased nitrogen availability to the host plant on parasitism by the specialist parasitoid Trioxys pallidus (Haliday). In laboratory experiments with walnut seedlings, a higher chlorophyll content index of the foliage in response to added nitrogen was correlated with a decrease in the number of mummies produced by female parasitoids over a 24-h period but an increase in the proportion and the size of female offspring. In field sampling of walnut orchards, there was no relationship between the percent parasitism of walnut aphids by T. pallidus and the chlorophyll content index of the trees. Nitrogen fertilizer and plant quality can clearly affect biological control and should be given greater consideration in integrated pest management.


New live screening of plant-nematode interactions in the rhizosphere.
Free living nematodes (FLN) are microscopic worms found in all soils. While many FLN species are beneficial to crops, some species cause significant damage by feeding on roots and vectoring viruses. With the planned legislative removal of traditionally used chemical treatments, identification of new ways to manage FLN populations has become a high priority. For this, more powerful screening systems are required to rapidly assess threats to crops and identify treatments efficiently. Here, we have developed new live assays for testing nematode responses to treatment by combining transparent soil microcosms, a new light sheet imaging technique termed Biospeckle Selective Plane Illumination Microscopy (BSPIM) for fast nematode detection, and Confocal Laser Scanning Microscopy for high resolution imaging. We show that BSPIM increased signal to noise ratios by up to 60 fold and allowed the automatic detection of FLN in transparent soil samples of 1.5 mL. Growing plant root systems were rapidly scanned for nematode abundance and activity, and FLN feeding behaviour and responses to chemical compounds observed in soil-like conditions. This approach could be used for direct monitoring of FLN activity either to develop new compounds that target economically damaging herbivorous nematodes or ensuring that beneficial species are not negatively impacted.