Characterization of ibuprofen removal by calcined spherical hydrochar through adsorption experiments, molecular modeling, and artificial neural network predictions.
Ibuprofen (IPF) is one of the most prescribed nonsteroidal anti-inflammatory drugs in recent times, but it is not readily removed in conventional wastewater treatments. Here, we investigate the adsorption characteristics of IPF onto calcined spherical hydrochar (CSH), which was synthesized through hydrothermal carbonization of sucrose followed by calcination. The adsorption experiments show that the equilibration time for IPF was 360 min, and a pseudo-second-order model was best fitted to the kinetic data. The isotherm data were best described by the Liu model with a theoretical maximum adsorption capacity of 95.6 mg/g. The thermodynamic data indicate the endothermic nature of the adsorption at 10-40 °C. The CSH was favorably regenerated and reused using methanol. In pH experiments, the IPF adsorption capacity declined gradually as pH rose from 2 to 8, dropped rapidly at pH 10, and became negligible at pH 12. The IPF adsorption to the CSH could occur through various adsorption mechanisms. Hydrogen-bond formation, π-π interactions, n-π* interactions, and electrostatic repulsion were explored and visualized with molecular modeling using CHEM3D. The Raman, FTIR, and XPS spectra suggest that π-π interactions could take place between the CSH and IPF. Considering the pKa value of IPF (4.91) and pHiep of the CSH (3.21), electrostatic repulsion between the negatively-charged CSH and anionic IPF could play a negative role in the adsorption. A pore-filling mechanism could contribute to the adsorption in view of the molecular size of IPF (9.43 Å × 7.75 Å × 6.23 Å) and the average pore diameter of the CSH (2.27 nm). In addition, hydrophobic interactions could be involved in the adsorption. Multi-factor adsorption experiments were executed with pH, temperature, CSH dosage, and initial IPF concentrations as input variables and IPF removal rate as an output variable, and an artificial neural network (ANN) model with a topology of 4:9:11:1 was developed to sufficiently describe the adsorption data (R > 0.99). Further analyses with additional experimental data confirm that the ANN model possessed good predictability for multi-factor adsorption.


Safety and Efficacy of a Novel Anterior Decompression Technique for Ossification of Posterior Longitudinal Ligament of the Cervical Spine.
Anterior cervical corpectomy and fusion (ACCF) for cervical ossification of the posterior longitudinal ligament (OPLL) is associated with a high incidence of surgery-related complications. A novel anterior decompression technique (vertebral body sliding osteotomy [VBSO]) has been developed to prevent such complications. This study attests the efficacy and safety of VBSO versus those of standard ACCF. Patients requiring surgery for cervical OPLL underwent VBSO (24 patients) or ACCF (38 patients). Operating time, estimated blood loss, neurologic outcomes, complications, and various radiographic parameters were investigated. The VBSO group showed a shorter mean operating time and less estimated blood loss versus the ACCF group. Sixteen patients in the ACCF group experienced various complications, namely neurologic deficit (two patients), cerebrospinal fluid leakage (four patients), graft migration (three patients), and pseudarthrosis (seven patients). In the VBSO group, only pseudarthrosis was reported (two patients). VBSO provides similar neurologic outcomes with a shorter operating time and less bleeding compared with ACCF. Surgeons do not need to directly manipulate the OPLL mass or dissect the interspace between the OPLL and dura mater. Therefore, this technique may decrease the incidence of surgery-related complications. Retrospective comparative study.


Foxtail Millet: A New Model for C4 Plants.
Arabidopsis and rice are major models for C3 plants, but we still lack a model for C4 plants. Recently, Yang and coworkers developed foxtail millet as a C4 plant model; with the rapid development of clustered regularly interspaced short palindromic repeats (CRISPR)/Cas technology, this will open a new era for plant functional studies and crop improvement.


Improving treatment with methotrexate in rheumatoid arthritis-development of a multimedia patient education program and the MiRAK, a new instrument to evaluate methotrexate-related knowledge.
To develop and test an evidence-based, multimedia patient education program (MPEP) about methotrexate (MTX) treatment for rheumatoid arthritis (RA) and a new measure of patient knowledge [Methotrexate in Rheumatoid Arthritis Knowledge test (MiRAK)]. The content of the MPEP and MiRAK was guided by concept-mapping workshops with patients (N = 24), literature review, health professional, and expert linguistic input. The MPEP and MiRAK underwent multiple stages of testing and revision with patients and health professionals. The MiRAK was administered to RA patients (N = 169) and its properties examined using the Rasch analyses. A subset of respondents (N = 131) repeated the MiRAK to determine test-retest reliability. A before-after pilot study with patients who had recently started MTX (N = 31) tested responsiveness of the MiRAK and feasibility and acceptability of the MPEP. A DVD of 24-minutes duration was produced that presents detailed, evidence-based information about MTX. The Rasch analyses of the 60 MiRAK items revealed that these could be summated into a single score. The MiRAK had good model fit, supporting internal construct validity, good internal consistency (person separation index; 0.84), test-retest reliability (ICC; 0.89), and ability to detect change (ES; 2.38). The before-after study suggested that patients could self-administer the MPEP, with the majority finding it informative and easy to use. We developed a MPEP about MTX treatment for RA, which was found to be user-friendly and easily implementable. The MiRAK is a new scale, testing a broad spectrum of MTX knowledge. Analyses revealed strong evidence for its validity and reliability.


Resveratrol Downregulates miR-31 to Promote T Regulatory Cells during Prevention of TNBS-Induced Colitis.
Colitis, an inflammatory bowel disease, is associated with aberrant regulation of the colonic mucosal immune system. Resveratrol, a natural plant product, has been found to exert anti-inflammatory properties and attenuate the development of murine colitis. In the current study, the role of microRNA (miR) in the ability of resveratrol to suppress colonic inflammation is examined. BALB/C mice with 2,4,6-Trinitrobenzenesulfonic acid solution (TNBS)-induced colitis, when treated with resveratrol, show improved clinical outcomes and reduce induction of inflammatory T cells (Th17 and Th1) while increasing CD4+Foxp3+ regulatory T cells (Tregs) and IL-10-producing CD4+ T cells. miR microarray analysis and polymerase chain reaction (PCR) validation from CD4+ T cells show treatment with resveratrol decreases the expression of several miRs (miR-31, Let7a, miR-132) that targets cytokines and transcription factors involved in anti-inflammatory T cell responses (Foxp3 and TGF-β). Transfection studies with miR-31 confirm that this miR directly regulates the expression of Foxp3. Lastly, analysis of public data from human patients with ulcerative colitis reveals that miR-31 expression is significantly increased when compared to controls. Together, the current study demonstrates that resveratrol-mediated attenuation of colitis may be regulated by miR-31 through induction of Tregs and miR-31 may serve as a therapeutic target for human colitis.


Ultrastructural study on the small blood vessels of human vocal cords.
Small blood vessels of human vocal cords were examined by electron microscopy. The endothelial cells contain a large number of filaments. Two kinds of filaments could be differentiated: Short intermediate filaments with a diameter of 10-12 nm, which were localized in the pericaryon, and bundles of thin filaments with a periodicity of 480 nm lying beneath the luminal cellular membrane. The basement membrane of capillaries, arteries, and veins was lamellate. Between the outermost, not fully closed lamellae, myocytes or pericytes could be seen. Both the lamellate basement membranes and the large number of intermediate filaments in the endothelial cells are discussed as stabilizing structures in blood vessels which are exposed to high mechanical forces. The bundles of cross-striated thin filaments may possibly increase the permeability of the vessel wall by their contraction, permitting the well-known fast development of edema in the vocal cords. The importance of Weibel-Palade bodies, which could be disclosed in the endothelial cells in large numbers, is not yet known.


Bleeding complications and liver injuries during phenprocoumon treatment: a multicentre prospective observational study in internal medicine departments.
Even after the recent approval of newer oral anticoagulants for clinical use, the vitamin K antagonist phenprocoumon remains an important treatment option for many patients. In order to quantify the hitherto "accepted" risks of phenprocoumon treatment, we analyzed adverse drug reactions (ADRs) that led to hospitalization on the internal medicine wards of four German pharmacovigilance centers. We prospectively analyzed ADRs leading to hospitalization on the internal medicine wards of the hospitals belonging to the German Network of Regional Pharmacovigilance Centers (Rostock, Greifswald, Jena, and the Sophien- und Hufeland-Klinikum in Weimar) in the years 2000 to 2008. The 851 patients hospitalized for a phenprocoumon-associated ADR accounted for 12.4% of the 6887 ADR-related hospitalizations in the period of the study. 723 (85%) were admitted for a hemorrhage, usually in the gastrointestinal tract (482 patients); 8 patients died as a consequence of hemorrhage associated with phenprocoumon exposure. Using drug utilization data for the catchment areas of the participating hospitals, we calculate a rate of 5 to 7 hemorrhages leading to hospitalization in an internal medicine ward per 1000 patient-years under phenprocoumon treatment. One-third of the patients who had a hemorrhage were taking other interacting drugs, mainly inhibitors of platelet aggregation and non-steroidal anti-inflammatory drugs. Among the patients who were taking phenprocoumon because of a history of thromboembolic events or for atrial fibrillation, 60% to 70% of those who had hemorrhages had an international normalized ratio (INR) that was above the upper limit of the therapeutic range. Phenprocoumon-associated impairment of liver function arose in 23 patients (2.7%). In this study, about one-eighth of all ADR-related admissions to hospital internal medicine wards were associated with phenprocoumon. There is a need for a comparative risk-benefit assessment of phenprocoumon and the newer oral anticoagulants under real-life conditions.


Elevated sL1-CAM levels in BALF and serum of IPF patients.
IPF is a form of interstitial pneumonia of unknown origin that has a poor prognosis for which current treatments are limited. Recent studies have shown that EMT plays a role in IPF and tumour metastasis. L1-CAM has also been linked to EMT during tumour development and tumour metastasis. Our aim was to determine prospectively the level of L1-CAM in IPF patients. Forty consecutive Chinese patients (with IPF, 16; LC, 12; and CC, 12), but no apparent lung or other organ's diseases were enrolled. Soluble L1-CAM (sL1-CAM), TGF-β1, PDGF, γ-INF levels in BALF and serum sL1-CAM were measured using ELISA. BALF sL1-CAM levels of IPF, LC and CC patients were 10.87 ± 0.88 ng/mL, 6.34 ± 0.67 ng/mL and 5.43 ± 0.65 ng/mL, respectively. BALF sL1-CAM concentration of IPF patients was significantly higher than that in LC and in CC patients. Besides, serum sL1-CAM levels in patients with IPF, LC and CC were 9.60 ± 1.41 ng/mL, 9.82 ± 0.72 ng/mL and 5.41 ± 1.07 ng/mL, respectively. The serum sL1-CAM levels in patients with IPF and LC were significantly higher than those in patients with CC (P < 0.001, respectively). The concentrations of sL1-CAM both in BALF and in serum of patients with IPF are markedly increased compared with controls. This indicates that L1-CAM might be involved in the pathogenesis of IPF as well as that of LC.


Monitoring bioaccumulation and toxic effects of hexachlorobenzene using the polyurethane foam unit method in the microbial communities of the Fuhe River, Wuhan.
Hexachlorobenzene (HCB) is a chlorinated aromatic hydrocarbon that was widely used for seed dressing in prevention of fungal growth on crops, and also as a component of fireworks, ammunition, and synthetic rubbers. Because of its resistance to degradation and mobility, HCB is widely distributed throughout the environment and is accumulated through food chains in different ecosystems. In this study, a preliminary investigation was carried out on the bioaccumulation and the toxic effects of HCB in the microbial (protozoan in particular) communities in the Fuhe River, Wuhan, a water body receiving industrial wastewaters containing HCB and other pollutants, using the standardized polyurethane foam units (PFU) method. Field samples were taken from eight stations established along the Fuhe River in January and August 2006. The concentration ratios of HCB in microbial communities and in water were 9.66-18.64, and the microbial communities accumulated 13.29-56.88 [ig/L of HCB in January and 0.82-10.25 microg/L HCB in August. Correlation analysis showed a negative correlation between the HCB contents in the microbial assemblage, and the number of species and the diversity index of the protozoan communities. This study demonstrated the applicability of the PFU method in monitoring the effects of HCB on the level of microbial communities.


The environment and male reproduction: The effect of cadmium exposure on reproductive function and its implication in fertility.
Cadmium is an environmental pollutant known as endocrine disruptor. Testis is particularly susceptible to cadmium, and testis injury occurs at high but even low levels of exposure. Cadmium reproductive toxicity is mediated by multiple mechanisms, including structural damage to testis vasculature and blood-testis barrier, inflammation, cytotoxicity on Sertoli and Leydig cells, oxidative stress mainly by means of mimicry and interference with essential ions, apoptosis, interference with selected signaling pathways and epigenetic regulation of genes involved in the regulation of reproductive function, and disturbance of the hypothalamus-pituitary-gonadal axis. The current review outlines epidemiological observational findings from environmental and occupational exposure in humans, and reports experimental studies in humans and animals. Lastly, a focus on the pathogenetic mechanisms of cadmium toxicity and on the specific mechanisms of cadmium sensitivity and resistance, particularly assessed in animal models, is included. Despite convincing experimental findings in animals and supporting evidences in humans identifying cadmium as reproductive toxicant, observational findings are controversial, suffering from heterogeneity of study design and pattern of exposure, and from co-exposure to multiple pollutants.


Production readiness assessment of low cost, multi-material, polymeric 3D printed moulds.
Fused Deposition Modelling (FDM) technology allows to choose a large variety of materials and it is widely used by companies and individuals nowadays. The cost effectiveness of rapid prototyping is achievable via FDM, that makes this technology useful for research and innovation. The application of 3D printing to aid production is the most common approach. Moreover, the use of 3D printing in prototypes result in a waste of material since no reuse is considered. In the following manuscript, this technology is applied to mould fabrication by achieving a low surface roughness at a modest cost compared to conventional manufacturing methods. Moreover, the possibility to use a combination of thermoplastic materials is analysed by examination of the CAD model optimized for Additive Manufacturing (AM) from scratch and was verified using metrology tools. Several moulds were finally built and applied to the specific case study of carbon fibre laminated components. This manuscript aims to analyse the manufacturing process by comparing the mould surface geometry before and after the smoothing process. The achieved tolerance between the produced moulds is ±0.05 mm that ensures the repeatability of the process from an industrial point of view; whilst the deviation between CAD and mould is ±0.2 mm. To combine an accurate FDM process together with chemical smoothing proved to be a powerful strategy to produce high quality components that can be inserted in the production process by means of traditional manufacturing techniques. This will aid to reduce the cost of standard manufacturing for low production batches and prototypes of carbon fibre composites.


Seasonal variation and hospital utilization for tuberculosis in Russia: hospitals as social care institutions.
Clinical management of tuberculosis in Russia involves lengthy hospitalizations, in contrast to the recommended strategy advocated by the World Health Organization. We used Fourier transform, spectral analysis and Student's t-test to analyse periodic and seasonal variations in admission and discharge rates for tuberculosis hospitalizations in 1999-2002, using routinely captured data from the Samara Region, Russia. Hospital admissions in colder months were significantly higher than in warmer months. The mean monthly adjusted number of admissions in colder and warmer months for all adults was 413 and 372 (P < 0.01), for unemployed adults 218 and 198 (P < 0.02) and for pensioners 104 and 82 (P < 0.05). Hospital discharges varied seasonally. Maximum differences between admissions and discharges occurred in colder months and minimum differences were observed in warmer months. As hospitalizations of tuberculosis patients in colder months fulfil an important social need, shifts to ambulatory care must be carefully managed.


The deletion variant of α2b-adrenergic receptor is associated with decreased risk in Alzheimer's disease and mild cognitive impairment.
A common genetic polymorphism of the α2b-adrenergic receptor (ADRA2B) resulting in a deletion of three glutamic acids located on the third intracellular loop of the protein, has been associated with memory formation enhanced by emotional events. Additionally, there are several studies documenting the involvement of this polymorphism in other types of cognition, such as episodic memory. The aim of this study was to investigate the possible relationship of this genetic variance with a common memory affecting disease, Alzheimer's disease. Our study was carried out in a total number of 311 Greek subjects, including 119 sporadic AD patients, 95 MCI cases and 97 controls. Genomic DNA was extracted from whole blood and the fragments containing the polymorphism were amplified by PCR analysis. A genotypic analysis of the APOE polymorphism was also carried out. A significant difference in the frequency of the ADRA2B genetic variation among the three groups was observed. Specifically, the deletion variant is more prevalent in controls than in AD and MCI patients. Our data demonstrate for the first time an independent contribution of the ADRA2B genetic polymorphism to memory impairment and we further suggest a possible protective role of the deletion variant against the disease development.


18F-FDG microPET imaging detects early transient response to an IGF1R inhibitor in genetically engineered rhabdomyosarcoma models.
Alveolar rhabdomyosarcoma (ARMS) and embryonal rhabdomyosarcoma (ERMS) are among the most common and most treatment resistant soft tissue sarcomas of childhood. Here, we evaluated the potential of (18)F-Fluorodeoxyglucose (FDG) as a marker of therapeutic response to picropodophyllin (PPP), an IGF1R inhibitor, in a conditional mouse model of ARMS and a conditional model of ERMS/undifferentiated pleomorphic sarcoma (UPS). Primary tumor cell cultures from Myf6Cre,Pax3:Fkhr,p53 and Pax7CreER,Ptch1,p53 conditional models of ARMS and ERMS/UPS were found to be highly sensitive to PPP (IC(50) values 150 and 200 nM, respectively). Animals of each model were then treated with 80 mg/kg/day PPP by intraperitoneal injection for 12 days and imaged by (18)F-FDG microPET. Tumor volumes on day 4 for PPP-treated ARMS and ERMS mice were lower than untreated control mouse tumor volumes, although treated tumors were larger than day 0. However, tumor FDG uptake was significantly reduced on day 4 for PPP-treated mice compared to pretreatment baseline or untreated control mice on day 4 (P < 0.05). Nevertheless, by day 12 tumor volumes and FDG uptake for treated mice had increased significantly, indicating rapidly evolving resistance to therapy. (18)F-FDG PET imaging is a potential imaging biomarker of molecular susceptibility to targeted agents early in treatment for this aggressive form of sarcoma, but may find best use serially for Phase I/II studies where chemotherapy and targeted agents are combined to cytoreduce tumors and abrogate Igf1r inhibitor resistance.


Kikuchi-Fujimoto Disease Triggered by Systemic Lupus Erythematosus and Mycoplasma pneumoniae Infection-A Report of a Case and a Review of the Literature.
Kikuchi-Fujimoto disease (KFD) is a necrotizing histiocytic lymphadenitis that was described for the first time in 1972 in Japan. Its etiology is still not fully understood. It has been reported in association with many different agents, diseases, and triggering factors without any conclusive result. To the best of our knowledge, we report for the first time a case of KFD with systemic lupus erythematosus in a child in association with a polymerase chain reaction (PCR)-positive throat swab for Mycoplasma pneumoniae. Although difficult to prove, the acute M. pneumoniae infection might have served as a triggering event for the development of KFD in our case. We encourage further studies to investigate a potential relationship between KFD and M. pneumoniae, which should also use PCR-based testing for this pathogen in patients with KFD.


Triacetyloleandomycin as inducer of cytochrome P-450 LM3c from rabbit liver microsomes.
A cytochrome P-450 LM3 isozyme has been isolated and purified to electrophoretic homogeneity from liver microsomes of New Zealand white rabbits treated with TAO. On the basis of N-terminal sequence analysis and Ouchterlony double diffusion experiments, this isozyme appeared to be closely related to P-450 LM3c isolated from control animals and was designated LM3c (TAO). Anti LM3c (TAO) IgG totally inhibited both erythromycin demethylase and P-450-TAO metabolite complex formation, two monooxygenase activities specifically stimulated by TAO in liver microsomes from male and female rabbits. Moreover, immunoquantitation experiments showed that the level of LM3c (TAO) was increased 10-15 times above control values in liver microsomes from TAO treated male and female rabbits. We conclude that an isozyme identical or closely related to LM3c is the major form of P-450 induced by TAO in rabbit liver microsomes.


Modulated Expression of Specific tRNAs Drives Gene Expression and Cancer Progression.
Transfer RNAs (tRNAs) are primarily viewed as static contributors to gene expression. By developing a high-throughput tRNA profiling method, we find that specific tRNAs are upregulated in human breast cancer cells as they gain metastatic activity. Through loss-of-function, gain-of-function, and clinical-association studies, we implicate tRNAGluUUC and tRNAArgCCG as promoters of breast cancer metastasis. Upregulation of these tRNAs enhances stability and ribosome occupancy of transcripts enriched for their cognate codons. Specifically, tRNAGluUUC promotes metastatic progression by directly enhancing EXOSC2 expression and enhancing GRIPAP1-constituting an "inducible" pathway driven by a tRNA. The cellular proteomic shift toward a pro-metastatic state mirrors global tRNA shifts, allowing for cell-state and cell-type transgene expression optimization through codon content quantification. TRNA modulation represents a mechanism by which cells achieve altered expression of specific transcripts and proteins. TRNAs are thus dynamic regulators of gene expression and the tRNA codon landscape can causally and specifically impact disease progression.


Characterization, kinetics and thermodynamics of biosynthesized uranium nanoparticles (UNPs).
The present study was carried out to explore the potential of the isolated bacterial strains isolated from Gabal El Sela in Eastern Dessert, Egypt for biosynthesis of uraninite nanoparticles intracellularly. The most potent bacterial strains associated (intra) with uranium nanoparticles were characterized by transmission electron microscope (TEM), Fourier transform infrared (FTIR) and Energy Dispersive X-ray (EDX). Studying factors affecting biosynthesis of uranium nanoparticles indicated that the optimum conditions were 6000 ppm uranium concentrations at pH 7.0 and temperature 30 °C ± 1 after five days with 10% biomass under shaking conditions and the maximum uranium uptake by MAM - U9 cells was 3300 ppm (55%) from uranyl nitrate solution and 3600 ppm (72%) from Sela rock sample. Results of TEM micrograph show those uranium nanoparticles (UNPs) with size ranging from 2.9 to 21.13 nm inside cells. The kinetics, isotherm and thermodynamics parameters of uranium uptaken by bacterial strain MAM -U9 have been determined and found to be a first order process (R2 = 9935), follows Langmuir isotherm (RL2 = 0.998) and the thermodynamics of ΔG = -9.715 kJmol-1, ΔH = 16.987 kJmol-1 and ΔS = 0.0881 kJmol-1 K-1 at 30 °C.


Pelviureteric junction obstruction: how much is the extent of the upper ureter with defective innervation needing resection?
It is well realized that Anderson-Hyne's pyeloplasty fails to improve the drainage pattern and renal functional parameters in a few cases of hydronephrosis because of pelviureteric junction (PUJ) obstruction. The purpose of this study is to delineate the lower extent of the abnormally innervated pelviureteric junction by S-100 immunohistochemistry, which requires surgical removal. Thirty pelviureteric junction (PUJ) specimens were analyzed by histology and by S-100 immunohistochemistry after serial sectioning of the resected ureter and compared with the variables age, calyceal separation, parenchymal thickness, differential renal function, glomerular filtration rate (GFR), and the measured constricted ureteral segment on gross examination. No significant correlation was noted (P >.05) when the histology was analyzed to find any association with any of the variables studied. The length of the visible constricted segment ranged from 2 mm to 15 mm (mean, 5.37 mm). The abnormally innervated segment was much longer than the length of the visible constricted segment in 24 and of the same length in 5 specimens. However, in 1 case, the abnormal innervation segment was shorter than the macroscopic constriction by 3 mm. The maximum difference in length between the visible constriction and the lower limit of defective innervation was 8 mm. The abnormally innervated ureteral segment below the PUJ in hydronephrosis is longer than the visible constricted segment at the time of surgery, and the ureter should be excised at least 8 mm or more beyond the visible lower limit of the constricted segment in cases of Anderson-Hyne's pyeloplasty.


Cloning of the promoter for the avian integrin beta 3 subunit gene and its regulation by 1,25-dihydroxyvitamin D3.
We have cloned the promoter of the avian beta 3 integrin gene. Using a probe comprising the 5'-untranslated region of an avian macrophage beta 3 cDNA, characterized by 5' rapid amplification of cDNA ends, several clones were isolated from an avian genomic library. One major and one minor transcriptional start site were identified at +1 and -47 base pairs, respectively, with the latter coinciding with a consensus sequence of an initiator. DNA sequence analysis of 800 base pairs 5' of the transcriptional start site fails to reveal either a TATA or CAAT box. In addition to an initiator, the first 200 base pairs contain consensus sequences for the binding of AP-1 and SP-1. A 3.5-kilobase fragment located immediately upstream of the transcriptional start site exhibits functional promoter activity, and deletion analysis reveals both suppressor and enhancer elements. In light of our observation that 1,25-dihydroxyvitamin D3 (D3) accelerates beta 3 transcription, we determined whether the avian beta 3 promoter contains a vitamin D response element (VDRE). Transfected reporter constructs containing the first 1.5 kilobases upstream of the major beta 3 transcriptional start site respond to D3 with enhanced luciferase activity. Analysis of this region reveals a classical VDRE consensus sequence, located at -756 to -770. The following observations support the hypothesis that this sequence represents a functional VDRE: 1) a 600-base pair genomic fragment or a 29-base pair oligomer, each containing the putative VDRE, respond to D3 when transfected into HD11 cells; 2) a 67-base pair DNA fragment derived from genomic DNA and containing the candidate beta 3 VDRE specifically binds the vitamin D receptor-retinoid X receptor beta complex; and 3) avian osteoclast precursor-derived nuclear extracts bind to a synthetic oligomer containing the beta 3 VDRE-like sequence and, in turn, are specifically displaced by unlabeled beta 3 VDRE and anti-vitamin D receptor antibody.


Effects of social activity participation and trust in the community on the transition of frailty classification in late-stage older adults: a 4-year prospective cohort study.
In Japan, frailty is a major risk factor for requiring long-term care, especially among older adults aged 75 years or older (ie, late-stage older adults). Both physical and social factors (eg, social activities, social support and community trust) are protective factors against frailty. However, few longitudinal studies have examined reversible change or stage improvement in frailty. This study investigated social activity participation and trust in the community that may affect the transition of late-stage older adults' frailty status. A mail-based survey was used to analyse the improvement or deterioration of frailty status (categorised as frailty, pre-frailty and robust) over a 4-year period. Binomial and multinomial logistic regression analyses were conducted; the transition in frailty classification was the dependent variable, while a change in social activity participation and the degree of trust in the community were the independent variables. Ikoma City, Nara Prefecture, Japan. 4249 community-dwelling older adults, aged ≥75 years, not requiring long-term care who completed a follow-up questionnaire from April to May 2016. Adjusting for confounding factors, no significant social factors were detected regarding improvement in frailty. However, an increase in exercise-based social participation was an improvement factor in the pre-frailty group (OR 2.43 (95% CI 1.08 to 5.45)). Conversely, a decrease in community-based social activity was a risk factor in the deterioration from pre-frailty to frailty (OR 0.46 (95% CI 0.22 to 0.93)). In the robust group, increased community-based social activity (OR 1.38 (95% CI 1.00 to 1.90)) was a protective factor against frailty, whereas decreased community trust was a risk factor (OR 1.87 (95% CI 1.38 to 2.52)). No social factors had a significant influence on the improvement of frailty in late-stage older adults. However, the promotion of exercise-based social participation was found to be important for improvement in the pre-frailty state. UMIN000025621.


Heterochromatin components in germline stem cell maintenance.
Stem cell maintenance requires expression of genes essential for stemness and repression of differentiation genes. How this is achieved remains incompletely understood. Here we investigate the requirement for central components of heterochromatin, Heterochromatin Protein 1 (HP1) and the histone H3 lys9 methyltransferase Su(var)3-9, in the Drosophila male germline stem cell (GSC) self-renewal, a paradigm for studying adult stem cell behavior. We found that mutations or RNAi knock down of HP1 or Su(var)3-9 cause loss of GSCs, accompanied by defects in cell division or survival and premature expression of the differentiation gene bag of marbles (bam). Conversely, over-expressing HP1 increases GSC number in wildtype flies and, strikingly, restores fertility to the sterile hopscotch (hop) mutant flies that lack niche signals. These results suggest that the central components of heterochromatin play roles including repressing differentiation genes in Drosophila male GSC maintenance.


Evidences for the involvement of an invertebrate goose-type lysozyme in disk abalone immunity: cloning, expression analysis and antimicrobial activity.
Lysozymes are ubiquitously distributed enzymes with hydrolytic activity against bacterial peptidoglycan and function to protect organisms from microbial pathogens. In this study, an invertebrate goose-type lysozyme, designated as abLysG, was identified in the disk abalone, Haliotis discus discus. The full-length cDNA of abLysG was 894 bp in length with an open reading frame of 789 bp encoding a polypeptide of 263 amino acids containing a signal peptide and a characteristic soluble lytic transglycosylase domain. Six cysteine residues and two catalytic residues (Glu(142) and Asp(168)) conserved among molluscs were also identified. The 3D homology structural models of abLysG and hen egg white lysozyme had similar conformations of the active sites involved in the binding of substrate. BAC sequence data revealed that the genomic structure of disk abalone g-type lysozyme comprises 7 exons with 6 intervening introns. The deduced amino acid sequence of abLysG shared 45.2-61.6% similarity with those of other molluscs and vertebrates. The TFSEARCH server predicted a variety of transcription factor-binding sites in the 5'-flanking region of the abLysG gene, some of which are involved in transcriptional regulation of the lysozyme gene. abLysG expression was detected in multiple tissues with the highest expression in mantle. Moreover, qPCR analysis of abLysG mRNA expression demonstrated significant up-regulation in gill in response to infection by live bacteria (Vibrio parahaemolyticus and Listeria monocytogenes), virus (viral hemorrhagic septicemia) and bacterial mimics (LPS and PGN). Expression of the recombinant disk abalone g-type lysozyme in Escherichia coli BL21, demonstrated its bacteriolytic activity against several Gram-negative and Gram-positive bacterial species. Collectively these data suggest that abLysG is an antimicrobial enzyme with a potential role in the disk abalone innate immune system to protect it from bacterial and viral infections.


COVID-19: Transatlantic Declines in Pediatric Emergency Admissions.
This cross-sectional study looked at the impact of the SARS-CoV-2/COVID-19 pandemic on pediatric emergency department (PED) attendances and admissions (as a proxy for severity of illness) in the United States and United Kingdom. Data were extracted for children and adolescents, younger than 16 years, attending Royal Manchester Children's Hospital (RMCH, United Kingdom), and Yale New Haven Children's Hospital (YNHCH, United States). Attendances for weeks 1 to 20 of 2020 and 2019 were compared, and likelihood of admission was assessed via calculation of odds ratios, using week 13 (lockdown) as a cutoff. Attendance numbers for each PED decreased in 2020 compared with 2019 (RMCH, 29.2%; YNHCH, 24.8%). Odds of admission were significantly higher after lockdown than in 2019-RMCH (odds ratio, 1.26; 95% confidence interval, 1.08-1.46) and YNHCH (odds ratio, 1.60; 95% confidence interval, 1.31-1.98). Although the absolute numbers of children and adolescents attending the PED and being admitted decreased after lockdown, the acuity of illness of those attending appears to be higher.


Detection of multiple types of human papillomavirus in a giant condyloma from a grafted patient. Analysis by immunohistochemistry, in situ hybridisation, Southern blot and polymerase chain reaction.
Immunosuppressed patients such as transplant recipients are known to develop multiple lesions suggestive of human papillomavirus (HPV) infection. A giant anal condyloma was obtained from a transplant patient; several fragments taken from different areas were examined for the presence of HPV DNA using in situ hybridisation, polymerase chain reaction (PCR) and Southern blot. Typical koilocytes were seen in routinely stained tissue sections, suggesting an HPV infection; furthermore, group specific HPV antigen was detected in one of four frozen fragments. Different results were obtained by in situ hybridisation according to the fragment tested. HPV types 6/11 were detected in each of the five fragments, frozen or fixed in Bouin's or formalin solutions. However, the number of HPV DNA positive cells and the intensity of the reaction greatly varied with the specimen. HPV 16 and 18 probes also reacted positively with the sample fixed in formalin; a stronger signal was observed with HPV 18 in one large focus than with HPV 16. HPV type 5 was detected in a few isolated cells of two frozen fragments. With the Southern blot technique, the profile of an HPV 6/11 was seen only in one of two frozen fragments; in this case, the bands were intense. A slight positive reaction was also obtained in one frozen fragment with HPV 16 probe. Four frozen fragments were analyzed with PCR: HPV 6/11 was detected in each fragment; HPV 18 was detected in the four samples but with different intensities; HPV types 5 and 16 did not show any positive signal. In conclusion, the lesion is an example of infection with several HPV types, demonstrated by three different techniques. This suggests the need for careful dermatological or colposcopic follow-up of transplant recipients, in order to prevent possible malignant transformation of anogenital lesions.


Principles of high-frequency ultrasonography for investigation of skin pathology.
Ultrasonography is a valuable diagnostic tool widely used in medicine. During the last three decades, this non-invasive skin imaging method has been extended to dermatology. High-frequency ultrasonography with higher than 20MHz scanners is well-established for measuring tumour thickness and skin thickness when treating inflammatory skin diseases such as scleroderma or psoriasis. High-frequency ultrasonography has become extremely helpful for the preoperative assessment of skin melanoma. The correlation between ultrasonic and histological measurements of melanomas thickness is significantly similarly good using transducers of 20, 75 or 100MHz frequency (r range from 0.895 to 0.99) and better compared with transducers of 7.5MHz frequency (r=0.76). The preoperative sonographically estimated thickness of skin melanoma is sometimes overestimated, because of an underlying inflammatory infiltrate and other reasons. Assessment of skin melanoma thickness using transducers of 100MHz frequency has better agreement with histology, compared with ultrasonography with 20MHz transducers. However, the ultrasonic penetration depth is limited to 1.5mm in case of 100MHz. The newer ultrasonic techniques such as high-frequency ultrasonography and colour Doppler sonography could be used for assessment of the tumour vascularization and its metastatic potential. The wide variety of diagnostic information provided by high-frequency ultrasonography undoubtedly improves the management of oncological and inflammatory skin conditions and underlines its essential position in dermatological practice.


Lysine derived cross-links are present in a non-elastin, proline-rich protein fraction of Iguana iguana eggshell.
1. Eggshell of Iguana iguana contains a variety of lysine-derived cross-linking amino acids apparently identical with some that occur in elastin. 2. Quantification of desmosine by amino acid analysis and radioimmunoassay gave estimates of 217 ng per mg and 109 ng per mg (dry weights), respectively. 3. [3H]NaBH4 reduction of eggshell protein established presence of lysine-derived aldehydes, allysine and allysine-aldol. 4. Enzymatic and chemical treatments indicate these cross-links occur in a non-elastin eggshell protein. 5. Iguana eggshell protein is unusually proline-rich, containing almost 440 proline residues per thousand.


New clinical and electrocardiographic classification in patients with idiopathic ventricular fibrillation.
The presence of early repolarization (ER) recently has been considered as a prognostic marker for sudden cardiac death in patients with idiopathic ventricular fibrillation (IVF), but there are certain numbers of IVF patients lacking ER. We aimed to clarify the clinical and electrocardiographic characteristics of the patients with IVF in the presence and absence of ER. We studied 64 consecutive IVF patients from the Japan Idiopathic Ventricular Fibrillation Study (J-IVFS) registry, which subjected with at least one episode of documented VF in the absence of structural heart diseases and excluding Brugada syndrome. We assessed clinical and electrophysiological characteristics in the IVF patients with and without ER. ER was defined as J-point elevation of >0.1 mV in either inferior or lateral leads. Twelve-lead electrocardiogram (ECG) demonstrated 24 (38%) of 64 patients with ER (ER[+] group) and the remaining 40 (62%) patients without ER (ER[-] group ). ER[+] group had a male predominance (92% for males) and ER[-] group revealed nearly equal distribution in both sexes. While no patients in ER[+] group showed intraventricular conduction disturbance (CD) with abnormal axis deviation and/or bundle branch block in ECG, 9 in ER[-] group had signs of CD (ER[-]/CD[+] subgroup). ER[-]/CD[+] subgroup had prolonged P-R interval and QRS duration compared to other patient groups. We found 3 distinct ECG patterns in IVF patients. In addition to the presence and absence of ER, there is a subgroup without ER demonstrating intraventricular CD, which represents a distinct clinical entity of IVF.


Identification of novel random amplified polymorphic DNAs (RAPDs) on the W chromosome of the domesticated silkworm, Bombyx mori, and the wild silkworm, B. mandarina, and their retrotransposable element-related nucleotide sequences.
Genomic DNAs were compared between males and females of the domesticated silkworm, Bombyx mori, strains C108, C137, J137, p50, and WILD-W (constructed by crossing a wild silkworm, B. mandarina, female with a male of strain C108) by polymerase chain reaction (PCR) with 700 arbitrary 10-mer primers. Four female-specific RAPDs (W-Kabuki, W-Samurai, W-Kamikaze, and W-Yamato) were found. The sex chromosome formulas of B. mori and B. mandarina are ZW (XY) for the female and ZZ (XX) for the male. The four female-specific RAPDs are assumed to be derived from the W chromosome because the other chromosomes are shared by both sexes. A computer search for deduced amino acid sequences of these four RAPDs revealed that all of them showed homology to previously reported amino acid sequences encoded in known retrotransposable elements from various organisms.


Genetic characterization of bluetongue virus serotype 9 isolates from India.
Recent incursions of bluetongue virus (BTV) into previously naive geographical areas have emphasised the need to better understand virus movement and epidemiology. Several bluetongue virus (BTV) serotypes are known to exist in India, and some serotype viruses have been isolated. However, the complete genome of not a single isolate is available to date. We report the complete genome sequence of one, and partial sequences of three other Indian isolates of BTV-9. Evolutionary relationships with segment-2 and -6 sequences of BTV isolates around the world, deduced using four different phylogenetic analyses and a similarity programme, show that BTV-9 (Eastern), BTV-9 (Western), and BTV-5 form a triad of equidistant, genetically distinct groups of viruses. The Indian BTV-9 isolates were closely related to Mediterranean and European BTV-9 isolates (Eastern topotype) based on segment-2 and -6 sequences. By contrast, segment-5 analyses clustered the Indian BTV-9 isolates with South African BTV-3 reference strain (98% identity), which belongs to one of the Western types. These results have implications on BTV origin and movement, genotyping, serotyping, and vaccine design.


Parkinsonian syndromes.
The primary role of magnetic resonance imaging (MRI) in the evaluation of patients with parkinsonian syndromes is traditionally thought to be the differentiation between neurodegenerative and symptomatic parkinsonisms. Non conventional MRI techniques, however, could improve the clinical diagnosis by detecting ultrastructural damage even in brain regions not suspected to be involved. Moreover, functional MRI provides useful information upon the pathophysiology of Parkinson's disease.


The Quick FICS: 5 and 10 Item Versions of the Family Inpatient Communication Survey.
Communication quality in the hospital impacts outcomes like satisfaction, depression, and anxiety for families, and assessment tools must be efficient and reliable. We developed the Quick FICS-5 and -10, shorter versions of the 30-item Family Inpatient Communication Survey (FICS). The Quick FICS were developed from the original FICS study of hospitalized patients 65+ and their surrogates. The development sample came from the original FICS-30 scale. The validation sample came from a randomized controlled trial of surrogates for adult ICU patients. Participants were family members of patients on medical ICU or inpatient medicine services at three hospitals in a Midwest metropolitan area. We evaluated validity and reliability using factor analysis, internal consistency, and associations with surrogate psychological and decision-making outcomes. In the development sample of 364 patient/surrogate dyads, most surrogates were adult children (66.8%), female (70.9%), and white (68.9%). We identified 5-item and 10-item surveys. Exploratory factor analysis supported an overall communication score for the FICS-5 and FICS-10, as well as information and emotional support subscales for the FICS-10. There was high internal reliability (Cronbach's alpha was 0.83 for the FICS-5 and 0.90 for the FICS-10; information and emotional support subscales were 0.89 and 0.75 respectively). There was good predictive validity when comparing FICS scores to outcomes six to eight weeks after discharge, including anxiety (P = -0.13; P = 0.0234), and satisfaction with the hospital stay (P = 0.48; P < 0.0001). Similarly, the validation sample (n = 188) revealed Cronbach's alpha ranging from 0.81 to 0.93 and significant correlations (P < 0.05) with concurrent distress, anxiety, depression, and decision regret. The Quick FICS offers efficient, valid, and reliable evaluation of communication quality in the hospital that can be useful for research and quality improvement.


Supratentorial astrocytomas of the midline in childhood--a review of treatment and prognosis.
Supratentorial astrocytomas in childhood are rare. In our series of 47 children (1979-1983) suffering from intracerebral tumors we observed three with astrocytomas situated in the midline. They had invaded the walls of the ventricles and caused hydrocephalus. The children were operated on by a right transventricular approach. We succeeded in total tumor removal in two cases and these children are well. One child (only subtotal extirpation had been possible) died. In our opinion, resignation is unfounded in such cases.


Fractal analysis in radiological and nuclear medicine perfusion imaging: a systematic review.
To provide an overview of recent research in fractal analysis of tissue perfusion imaging, using standard radiological and nuclear medicine imaging techniques including computed tomography (CT), magnetic resonance imaging (MRI), ultrasound, positron emission tomography (PET) and single-photon emission computed tomography (SPECT) and to discuss implications for different fields of application. A systematic review of fractal analysis for tissue perfusion imaging was performed by searching the databases MEDLINE (via PubMed), EMBASE (via Ovid) and ISI Web of Science. Thirty-seven eligible studies were identified. Fractal analysis was performed on perfusion imaging of tumours, lung, myocardium, kidney, skeletal muscle and cerebral diseases. Clinically, different aspects of tumour perfusion and cerebral diseases were successfully evaluated including detection and classification. In physiological settings, it was shown that perfusion under different conditions and in various organs can be properly described using fractal analysis. Fractal analysis is a suitable method for quantifying heterogeneity from radiological and nuclear medicine perfusion images under a variety of conditions and in different organs. Further research is required to exploit physiologically proven fractal behaviour in the clinical setting. • Fractal analysis of perfusion images can be successfully performed. • Tumour, pulmonary, myocardial, renal, skeletal muscle and cerebral perfusion have already been examined. • Clinical applications of fractal analysis include tumour and brain perfusion assessment. • Fractal analysis is a suitable method for quantifying perfusion heterogeneity. • Fractal analysis requires further research concerning the development of clinical applications.


Internal neurolysis or ligament division only in carpal tunnel syndrome--results of a randomized study.
In a series of patients with clinically and neurophysiologically well defined carpal tunnel syndrome a randomization has been made into two groups, one for operation with internal neurolysis and a microscopical technique, and the other group for cutting of the carpal ligament (flexor retinaculum) alone. The two groups have been compared postoperatively regarding clinical and neurophysiological parameters. All patients improved, 89% in both groups considered themselves totally free of symptoms at follow-up examinations but there was no significant difference in any parameter between the two groups. As a conclusion the use of internal neurolysis cannot be recommended as a routine procedure in carpal tunnel syndrome.


Inhibition of intestinal sodium-dependent inorganic phosphate transport by fibroblast growth factor 23.
The mechanisms by which fibroblast growth factor 23 (FGF23) alters inorganic phosphate (Pi) homeostasis is not entirely clear. In the present study, we examined the effect of FGF23 on intestinal sodium-dependent Pi transport in mice. Injection of FGF23(R179Q) markedly reduced serum Pi and 1,25(OH)2D3 levels in normal mice. Those animals show the reduction of intestinal sodium-dependent Pi transport activity and the amount of type IIb sodium-dependent Pi cotransporter (type IIb NaPi) protein in the brush border membrane vesicles. In vitamin D receptor null mice (VDR-/-), FGF23(R179Q) had no effect on intestinal sodium-dependent Pi transport activity and type IIb NaPi protein levels. The present study suggests that FGF23(R179Q) reduces intestinal sodium-dependent Pi transport activity and type IIb NaPi protein levels by a mechanism that is dependent on VDR.


Three-dimensional representation of the human cochlea using micro-computed tomography data: presenting an anatomical model for further numerical calculations.
We present a complete geometric model of the human cochlea, including the segmentation and reconstruction of the fluid-filled chambers scala tympani and scala vestibuli, the lamina spiralis ossea and the vibrating structure (cochlear partition). Future fluid-structure coupled simulations require a reliable geometric model of the cochlea. The aim of this study was to present an anatomical model of the human cochlea, which can be used for further numerical calculations. Using high resolution micro-computed tomography (µCT), we obtained images of a cut human temporal bone with a spatial resolution of 5.9 µm. Images were manually segmented to obtain the three-dimensional reconstruction of the cochlea. Due to the high resolution of the µCT data, a detailed examination of the geometry of the twisted cochlear partition near the oval and the round window as well as the precise illustration of the helicotrema was possible. After reconstruction of the lamina spiralis ossea, the cochlear partition and the curved geometry of the scala vestibuli and the scala tympani were presented. The obtained data sets were exported as standard lithography (stl) files. These files represented a complete framework for future numerical simulations of mechanical (acoustic) wave propagation on the cochlear partition in the form of mathematical mechanical cochlea models. Additional quantitative information concerning heights, lengths and volumes of the scalae was found and compared with previous results.


Effects of low- and high-frequency repetitive transcranial magnetic stimulation on long-latency auditory evoked potentials.
Long-latency auditory event potentials (LLAEPs) involving local and global auditory processes have been investigated to examine the impact of low-frequency (LF) and high-frequency (HF) repetitive transcranial magnetic stimulation (rTMS) on the cortical excitability of the temporal cortex. We hypothesized that both stimulation frequencies have the same modulation effect, in accordance with clinical data showing a reduction in auditory verbal hallucinations (AVHs) after LF and HF temporal rTMS in patients with schizophrenia. With 30 right-handed healthy volunteer participants enrolled in a crossover trial, we analyzed LLAEPs before and after LF- and HF-rTMS of the left temporal cortex. While we observed no changes in latencies, we did observe a similar inhibitory action of both rTMS frequencies on LLAEP amplitudes. Analysis of surface potential maps and cortical generators revealed some differences regarding auditory processes: HF-rTMS produced earlier, more diffuse, and more right-lateralized effects than LF-rTMS. Beyond a local impact, rTMS exerted a remote modulation influence on the frontal cortex that might be involved in attentional processes. This association could explain the therapeutic effect of temporal HF-rTMS on AVH.


Metabolic effects of branched chain amino acids in patients with severe pancreatitis.
Twenty-four patients with acute severe pancreatitis were randomised to receive total parenteral nutrition for 7 days with one of two isocaloric (35 kcal/kg/day) and isonitrogenous (0.16 g/kg/day) programmes containing either a low (15.5% w/w (control group)) or a high (57%) content of branched chain amino acids (BCAA (BCAA group)). During treatment, the nitrogen balance was similar in both groups. The concentrations of serum protein, albumin, prealbumin and retinol-binding protein did not differ between the groups. The plasma concentrations of BCAA measured 2 h after discontinuation of amino acid infusions rose in the BCAA group. In urine, only the concentrations of valine increased as compared with those of control patients. Serum glucose levels were higher in the BCAA group than in the control group, although the BCAA group received slightly more insulin than the control group in order to keep the blood glucose concentration below 10 mmol/l. The results suggest that BCAA-enriched solutions may stimulate gluconeogenesis without affecting catabolism.


[Implementation of Continuity of Care in Everyday Care - A Comparison Between two Psychiatric Hospitals].
The rigid separation of outpatient and inpatient care in the German health care system prevents continuity of care, although it has been shown to be of great importance for psychiatric patients. This study analyzes continuity of care of a model hospital with a global treatment budget according to § 64b SGB V and constant treatment staff across all settings in comparison to a control hospital with regular financing without such a team. In a prospective cohort study with a 20-month observation period, we collected data on continuity of care of 220 model and 215 control clinic patients. The model clinic achieved significant higher continuity of care than the control clinic, both during inpatient treatment at the time of recruitment and across all settings during the observation period. A global treatment budget can create the necessary conditions for more flexible psychiatric care and better implementation of continuity of care.


Recall of physical activity advice was associated with higher levels of physical activity in colorectal cancer patients.
The present study tested the hypothesis that recall of receiving physical activity (PA) advice would be associated with higher levels of PA in patients with a diagnosis of colorectal cancer (CRC). Colorectal cancer patients who were diagnosed in 2010 or 2011, and had been treated in the English National Health Service (NHS). 17,753 respondents completed at least one section of the survey relevant to the current study and after exclusion of 171 with dementia (since results relied on recall), 15,254 had complete data for the current study. 60% were male, 67% were >65 years and 96% were from a white ethnic group. Patients completed the 'Living with and Beyond Colorectal Cancer' Patient-Reported Outcome Measures (PROMS) survey in 2013. The survey included questions on receiving exercise advice/information ('PA advice'), and the frequency of currently doing at least 30 min of brisk PA per day ('PA level': 0, 1-4 or 5-7 days, within the past week; with the top category meeting UK guidelines). A third of respondents (31%) recalled receiving PA advice. Independent of demographics and treatment, patients who recalled having PA advice were more likely to be currently doing some brisk PA (51% in the advice group vs 42% in the no advice group; OR 1.74, 95% CI 1.60 to 1.90; p<0.001), and more likely to be meeting PA guidelines (25% vs 20%; OR 1.70, CI 1.54 to 1.88; p<0.001). Recalling being given PA advice after a diagnosis of CRC was associated with higher levels of PA. However, less than a third of patients recalled receiving advice. Future research should examine the context in which advice is given and randomised trials are required. However, encouraging clinicians working with patients with CRC to give brief PA advice is warranted and may help improve outcomes for CRC survivors.


Transformation of oocysts from several coccidian species by heat treatment.
The transformation of sporocysts in oocysts of Eimeria caviae, E. intestinalis, E. nieschulzi, E. separata, E. tenella, Isospora canis, I. heydorni, and Toxoplasma gondii by heat treatment was examined. Fresh unsporulated oocysts from these species were heated at 50 degrees or 55 degrees C for less than 5 min and cultivated at 25 degrees C for 1 week. No transformation of sporocysts was observed in the sporulated oocysts following heating at 55 degrees C, but sporulated oocysts of Tyzzeria and Caryospora types were found in some I. canis and I. heydorni oocysts after heating at 50 degrees C followed by cultivation. A few sporulated oocysts of the Isospora type were observed in E. intestinalis oocysts after cultivation. All transformed sporulated oocysts contained eight sporozoites. In contrast, the number of sporocysts varied from two to 0. These results indicate that sporocyst formation in oocysts was affected by heat treatment. The relationship between the total numbers of sporozoites and sporocysts in the transformed oocysts was consistent with that of the "Octozoic" group classified by Hoare.


AMPK Maintains Cellular Metabolic Homeostasis through Regulation of Mitochondrial Reactive Oxygen Species.
Reactive oxygen species (ROS) are continuously produced as a by-product of mitochondrial metabolism and eliminated via antioxidant systems. Regulation of mitochondrially produced ROS is required for proper cellular function, adaptation to metabolic stress, and bypassing cellular senescence. Here, we report non-canonical regulation of the cellular energy sensor AMP-activated protein kinase (AMPK) by mitochondrial ROS (mROS) that functions to maintain cellular metabolic homeostasis. We demonstrate that mitochondrial ROS are a physiological activator of AMPK and that AMPK activation triggers a PGC-1α-dependent antioxidant response that limits mitochondrial ROS production. Cells lacking AMPK activity display increased mitochondrial ROS levels and undergo premature senescence. Finally, we show that AMPK-PGC-1α-dependent control of mitochondrial ROS regulates HIF-1α stabilization and that mitochondrial ROS promote the Warburg effect in cells lacking AMPK signaling. These data highlight a key function for AMPK in sensing and resolving mitochondrial ROS for stress resistance and maintaining cellular metabolic balance.


Use of sunless tanning products among US adolescents aged 11 to 18 years.
To describe the prevalence and correlates of the use of sunless tanning products among US adolescents and their association with UV radiation exposure behaviors, including indoor tanning, sunburn experiences, and use of sunscreen while outdoors. Telephone-based, random-digit-dialed, cross-sectional survey conducted from July 1 through October 30, 2004. Telephone-accessible households with resident adolescents living with parents or caregivers in the mainland United States. Nationally representative, population-based sample of 1600 adolescents aged 11 to 18 years and their caregivers. Prevalence of recent (past-year) use of sunless tanning products and UV radiation exposure behaviors. The prevalence of self-reported use of sunless tanning products in the past year among US adolescents was 10.8%. Adolescent users of these products were more likely to be older and female, to perceive a tanned appearance as desirable, to have a parent or caregiver who used sunless tanning products, and to hold positive beliefs or attitudes about these products. Use of sunless tanning products was independently associated with indoor tanning and higher frequency of sunburn but not with use of sunscreen. Among US adolescents, 10.8% used sunless tanning products in the past year; this practice was associated with risky UV radiation exposure-related behaviors. Adolescents, therefore, must be educated about these products and the importance of avoiding indoor tanning and practicing sun-protective behaviors.


Balancing risks? Responses and non-responses of mayfly larvae to fish and stonefly predators.
In a series of laboratory experiments we examined the hypothesis that larvae of stream mayflies would respond to the presence of two different types of predators in such a way as to minimize their risk of being consumed by each. Positioning of larvae (whether they frequent the top, sides, or bottom of stones) of Baetis tricaudatus and Ephemerella subvaria was altered by the presence of predaceous stoneflies (Agnetina capitata) with a larger proportion of the population occurring on the upper surfaces, where the probability of encountering the predator was lowest. The presence of a benthivorous fish (Cottus bairdi) had no significant effects on positioning of the mayfly larvae. Lack of fish effects may reflect an inability of the mayflies to detect or respond to sculpins, or alternately may indicate that sculpins do not normally present a important predation risk for these mayflies. Failure of mayfly prey to account for fish predators when responding to the presence of stoneflies appcars to explain facilitation previously observed between stoneflies and sculpins.


Whole-Exome Sequencing Study of Extreme Phenotypes of NAFLD.
Nonalcoholic fatty liver disease (NAFLD) is a heterogeneous disease with highly variable outcomes. Patients with simple steatosis typically experience a benign course, whereas those with more advanced liver injury, nonalcoholic steatohepatitis (NASH), and advanced stage fibrosis suffer increased risk for complications such as cirrhosis, hepatic decompensation, and liver cancer. Genetic variants in patatin-like phospholipase domain-containing 3 (PNPLA3) and transmembrane 6 superfamily member 2 (TM6SF2) and clinical factors including diabetes, obesity, and older age increase a patient's risk for NASH, advanced fibrosis, and worse outcomes. Despite substantial investigation and identification of some common variants associated with NAFLD and advanced fibrosis, the genetics and functional mechanisms remain poorly understood. This study aimed to identify genetic variants by whole-exome sequencing of NAFLD phenotypes to provide novel insights into mechanisms behind NAFLD pathogenesis and variability. We sequenced 82 patients with liver biopsy-confirmed NAFLD and 4455 population controls. NAFLD patients were divided into extreme phenotypes based on liver fibrosis stage and clinical risk factors to investigate rare variants that might predispose to or protect from advanced NAFLD fibrosis. We compared NAFLD extremes to each other and individually to population controls, exploring genetic variation at both the single-variant and gene-based level. We replicated known associations with PNPLA3 and TM6SF2 and advanced fibrosis, despite sample-size limitations. We also observed enrichment of variation in distinct genes for progressor or protective NAFLD phenotypes, although these genes did not reach statistical significance. Conclusion: We report the first whole-exome sequencing study of genetic variation in liver biopsy-confirmed NAFLD susceptibility and severity, using a small cohort of extreme NAFLD phenotypes and a large cohort of population controls.


Predictors of Women's Awareness of the Benefits and Harms of Mammography Screening and Associations with Confusion, Ambivalence, and Information Seeking.
In recent years, there has been a shift toward promoting informed decision making for mammography screening for average-risk women in their 40s. Professional organizations such as the American Cancer Society and U.S. Preventive Services Task Force recommend that women weigh the potential benefits and harms of mammography prior to initiating screening. This decision-making process assumes that women are aware of both the benefits and harms of screening, yet little is known about the prevalence and antecedents of such awareness. Moreover, it is conceivable that women who are aware of both the benefits and harms may interpret this information as conflicting - which could be concerning, as researchers have documented adverse effects of exposure to conflicting health information in prior research. Using data from a population-based survey of U.S. women aged 30-59 (N = 557), the current study found that awareness of mammography's harms is relatively low compared to awareness of benefits. Health news exposure and interpersonal communication about health were associated with greater awareness of harms. In addition, women's awareness of both the benefits and harms was positively associated with confusion about breast cancer screening recommendations, ambivalence about getting a mammogram, and mammogram-related information seeking from online sources. Implications for cancer screening communication are discussed.


[In favour of a systemic vision of liaison psychiatry].
One of the problems of consultation-liaison psychiatry is the absence of request of the patient. Indeed, the patients do not recognize their disorder and prefer to go to the emergency unit in a general hospital. Thus, we meet in the emergency unit or in medical unit (liaison psychiatry activity). This is the reason why this first meeting has to be prepared. Consultation-liaison Psychiatry proposes to provide medical staff with the competences developed by psychiatry, and the denomination: Consultation and Liaison Psychiatry, indicates the bipolarity of its practice according to whether the intervention is addressed to the patient (consultation) or to the staff (liaison). However collaboration is sometimes difficult and the psychiatrist often meets with resistance. This is the reason why psychiatrists must work on their integration in the general hospital. Indeed, the psychiatrist works in an institution which is unfamiliar and he/she must adapt and create new practices if it is going to work. It is now clearly established that consultation-liaison psychiatry is not limited to consultations with patients, but is based on collaboration with medical staff. There are various ways of studying human problems: psychoanalysis, cognitive therapy, behavioural therapy. It is also possible to focus interest on the communication between individuals. The systemic therapies are interested in the interactions more than with any other aspect of reality, and this always from a pragmatic point of view. This concept is based on a series of designs. First of all, an intervention by problem solving aims at a change: the question is to know how a problem is maintained, hic et nunc. Secondly, humans are a sum of training by tests and errors. Finally, what we call reality is only our perception of reality: the human conflicts emerge when two persons assign a different direction to a reality which is perceived jointly. The human relationship can be defined as interaction circles, which we propose to use in our practice of consultation-liaison psychiatry. The question is no longer to know why the subject has a problem but to know how to resolve it. The call for a consultation of psychiatry is often the result of an interaction between patient and staff. We propose an assessment of the consultation-liaison-psychiatry's demand so as to offer a concrete response to medical teams and patients. 1. First of all, the claimant should be known. This first question is to be asked before even meeting the patient. In the majority of cases, it is the medical staff that suffers from the situation (and wants a change). To work only on the patient, discredits the psychiatric intervention. 2. The definition of the problem is a concrete question, which we want based on the facts and not on the comments. That which requires the consultation (the patient, his/her family or the medical team) awaits concrete answers from the psychiatrist. It is important that the objectives of the intervention are defined before meeting the patient. These preliminary exchanges facilitate the consultation-liaison intervention. 3. By knowing the solutions tried before the request for psychiatric help, the psychiatrist will be able to know the measures already tried (whether they were effective or not). 4. By proposing minimal changes, it defines small but obtainable objectives, which will be as much as to increase therapeutic alliance and the tolerance of patients sometimes difficult to understand. 5. Finally, the consultation-liaison psychiatrist must know the language of his/her interlocutors. Interdisciplinary alliance is a fundamental condition for the success of the intervention: like the patients, the medical staff must feel understood to be able to cooperate. To develop this alliance and to inhibit resistance, it is important to speak the language of the claimant. The demand will progressively become interventions, more adapted, especially when the psychiatrist is recognized and appreciated by the team, like a good consultant, credible and concrete. Thus, mentally distressed patients can benefit from psychiatric care (although they do not request it). However, two phases appear essential. First, we have to define the demand and the claimant (environment, medical staff and patient) and second, we have to support the integration of the psychiatrist in the functioning of the medical unit. Our systemic vision of the consultation-liaison psychiatry proposes a pragmatic collaboration, centred on the problem. This approach allows the patient to prepare to meet the psychiatrist, and does not a priori discredit the intervention. Presented by the staff, who know the problem in concrete terms and are ready to answer it in a concrete way, this mode of intervention is only the first step of subsequent psychiatric care.


Corrigendum: A SCANO Nomogram for Individualized Prediction of the Probability of 1-Year Unfavorable Outcomes in Chinese Acute Ischemic Stroke Patients.
[This corrects the article on p. 531 in vol. 11, PMID: 32695060.].


Insulin-like growth factors I and II in the sole Solea senegalensis: cDNA cloning and quantitation of gene expression in tissues and during larval development.
Insulin-like growth factors I and II (IGF-I and IGF-II) play an important role as modulators of development, growth, and reproduction. This study aimed to isolate the IGF-I and IGF-II cDNAs and determine their temporal expression pattern in different organs and throughout larval development in Senegal sole. The rapid amplification of cDNA ends (RACE) was used to obtain both full-length IGFs sequences. A high sequence similarity with other teleosts sequences was observed. Domains B and A revealed as the most evolutionary conserved. Steady-state copy numbers of IGF-I and IGF-II were also quantified in different Senegal sole tissues by real-time PCR. IGF-I and IGF-II expressed ubiquitously with the highest mRNA levels in liver (88 x 10(6) molecules/microg total RNA) and gills (14.0 x 10(6) molecules/microg total RNA) respectively. IGF-II mRNA levels were higher than IGF-I in prehatching embryos and premetamorphic larvae with a significant drop before the commencement of eye migration in metamorphosis. The abundance of IGF-II transcripts correlated positively with the growth rate during larval development. The putative role of IGF-II on metamorphosis and larval growth is discussed.


A complete volume profile for the reversible binding of camphor to cytochrome P450(cam).
The effect of pressure on the kinetics and thermodynamics of the reversible binding of camphor to cytochrome P450(cam) was studied as a function of the K(+) concentration. The determination of the reaction and activation volumes enabled the construction of the first complete volume profile for the reversible binding of camphor to P450(cam). Although the volume profiles constructed for the reactions conducted at low and high K(+) concentrations are rather similar, and both show a drastic volume increase on going from the reactant to the transition state and a relatively small volume change on going from the transition to the product state, the position of the transition state is largely affected by the K(+) concentration in solution. Similarly, the activation volume determined for the dissociation of camphor is influenced by the presence of K(+), which reflects changes in the ease of water entering the active site of camphor-bound P450(cam) that depends on the K(+) concentration. Careful analysis of the components that contribute to the observed volume changes allowed the estimation of the total number of water molecules expelled to the bulk solvent during the binding of camphor to P450(cam) and the subsequent spin transition. The results are discussed in reference to other studies reported in the literature that deal with the kinetics and thermodynamics of the binding of camphor to P450(cam) under various reaction conditions.


Bivalirudin versus heparin and protamine in off-pump coronary artery bypass surgery.
Bivalirudin is a short-acting direct thrombin inhibitor, with advantages over unfractionated heparin for anticoagulation in cardiac surgery. We hypothesized that bivalirudin is not associated with a clinically important increase in blood loss compared with heparin with protamine reversal in patients undergoing off pump coronary artery bypass (OPCAB) surgery. We also assessed flow with angiography at 3 months using a modified Thombolysis in Myocardial Infarction (TIMI) grade in the grafted coronary arteries. One hundred patients were randomly assigned to receive bivalirudin (0.75 mg/kg bolus, 1.75 mg/kg/h infusion) or heparin (150 to 300 U/kg bolus) with protamine reversal. A median of 3 (range, 1 to 5) grafts were inserted per patient. Blood loss for the 12 hours after study drug initiation in the bivalirudin group (median, 793 mL; interquartile range, 532 to 1,214 mL; range, 320 to 4,909 mL; n = 50) was not significantly greater than in the heparin group (median, 805 mL; interquartile range, 517 to 1,117 mL; range, 201 to 2,567 mL; n = 50; p = 0.165). Median graft flow was 3.0 in the bivalirudin group (n = 40) and 2.67 in the heparin group (n = 39; p = 0.047). The bivalirudin group had more patients with grade 3 (ie, full) flow in at least 1 graft (100% versus 90%; p = 0.04), a trend toward more patients with grade 3 flow in all grafts (60% versus 38%; p = 0.06), and more grafts with grade 3 flow (82% versus 67%; p = 0.03). Anticoagulation for OPCAB surgery with bivalirudin was feasible without a clinically important increase in perioperative blood loss. Graft flow was better in the bivalirudin patients; the impact of this on clinical outcomes requires a larger study.


Vitamin D Treatment during Pregnancy and Maternal and Neonatal Cord Blood Metal Concentrations at Delivery: Results of a Randomized Controlled Trial in Bangladesh.
Vitamin D improves absorption of calcium; however, in animal studies vitamin D also increases the absorption of toxic metals, such as lead and cadmium. We examined maternal and neonatal cord blood levels of lead, cadmium, manganese, and mercury after supplementation with vitamin D during pregnancy. The Maternal Vitamin D for Infant Growth trial was a randomized, placebo-controlled, multi-arm study of maternal vitamin D supplementation during pregnancy in Dhaka, Bangladesh (NCT01924013). Women were randomized during their second trimester to blinded weekly doses of placebo or 4,200, 16,800, or 28,000 IU of vitamin D3 throughout pregnancy. Each group had 118-239 maternal blood specimens and 100-201 cord blood samples analyzed. Metals were measured using inductively coupled plasma mass spectrometry. Unadjusted estimates from linear regression models were expressed as percentage differences. Cord blood cadmium was analyzed as detectable or undetectable with log-binomial regression. Maternal cadmium, mercury, and manganese levels were nearly identical across groups. Maternal lead levels were 6.3%, 7.4%, and 6.0% higher in the treatment groups (4,200, 16,800, and 28,000 IU, respectively) vs. placebo; however, 95% confidence intervals (CIs) showed that differences from 4.1% lower to 20% higher were compatible with the data. In treatment groups (4,200, 16,800, 28,000 IU) vs. placebo, neonatal cord blood lead levels were 8.5% (95% CI: -3.5, 22), 16% (95% CI: 3.3, 30), and 11% (95% CI: 0.4, 23) higher and had higher risk of detectable cadmium, relative risk (RR)=2.2 (95% CI: 1.3, 3.7), RR=1.4 (95% CI: 0.8, 2.5), RR=1.7 (95% CI: 1.0, 2.9). Vitamin D supplementation from the second trimester of pregnancy did not influence maternal cadmium, mercury, or manganese levels at delivery. Vitamin D was associated with nonsignificant increases in maternal lead and with significant increases in cord blood lead and cadmium. These associations were not dose dependent. Given that there are no safe levels of metals in infants, the observed increases in cord blood lead and cadmium require further exploration. https://doi.org/10.1289/EHP7265.


A biomimetic multilayer nanofiber fabric fabricated by electrospinning and textile technology from polylactic acid and Tussah silk fibroin as a scaffold for bone tissue engineering.
To engineer bone tissue, a scaffold with good biological properties should be provided to approximate the hierarchical structure of collagen fibrils in natural bone. In this study, we fabricated a novel scaffold consisting of multilayer nanofiber fabrics (MLNFFs) by weaving nanofiber yarns of polylactic acid (PLA) and Tussah silk fibroin (TSF). The yarns were fabricated by electrospinning, and we found that spinnability, as well as the mechanical properties of the resulting scaffold, was determined by the ratio between polylactic acid and Tussah silk fibroin. In particular, a 9:1 mixture can be spun continuously into nanofiber yarns with narrow diameter distribution and good mechanical properties. Accordingly, woven scaffolds based on this mixture had excellent mechanical properties, with Young's modulus 417.65MPa and tensile strength 180.36MPa. For nonwoven scaffolds fabricated from the same materials, the Young's modulus and tensile strength were 2- and 4-fold lower, respectively. Woven scaffolds also supported adhesion and proliferation of mouse mesenchymal stem cells, and promoted biomineralization via alkaline phosphatase and mineral deposition. Finally, the scaffolds significantly enhanced the formation of new bone in damaged femoral condyle in rabbits. Thus, the scaffolds are potentially suitable for bone tissue engineering because of biomimetic architecture, excellent mechanical properties, and good biocompatibility.


Mediterranean diet is inversely associated with steatosis and fibrosis and decreases ten-year diabetes and cardiovascular risk in NAFLD subjects: Results from the ATTICA prospective cohort study.
We assessed the association of Mediterranean diet with NAFLD and their interaction in predicting ten-year diabetes onset and first fatal/non-fatal cardiovascular disease (CVD) incidence. The ATTICA prospective observational study in Athens, Greece included 1,514 men and 1,528 women (>18 years old) free-of-CVD at baseline. Liver steatosis and fibrosis indices were calculated. Mediterranean diet adherence was assessed through MedDietScore. At the ten-year follow-up visit, CVD evaluation was performed in an a priori specified subgroup of n = 2,020 participants and diabetes onset in n = 1,485 free-of-diabetes participants. MedDietScore was inversely associated with steatosis and fibrosis; e.g. in the case of the TyG index the Odds Ratio (OR) of the 3rd vs. 1st MedDietScore tertile was = 0·53, [95% Confidence Interval (95% CI) (0·29, 0·95)] and the associations persisted in multi-adjusted models. NAFLD predicted incident diabetes prospectively over a ten year period [HR = 1·87, 95% CI (0·75, 4·61)] and the association remained significant only in subjects with low MedDietScore (below median) whereas diabetes onset among subjects with higher MedDietScore was not influenced by NAFLD. Similarly, NAFLD predicted CVD [Hazard Ratio (HR) = 3·01, 95%CI(2·28, 3·95)]; the effect remained significant only in subjects with MedDietScore below median [HR = 1·38, 95% CI (1·00, 1·93)] whereas it was essentially null [HR = 1·00,95% CI (0·38, 2·63)] among subjects with higher score. Mediation analysis revealed that adiponectin and adiponectin-to-leptin ratio were the strongest mediators. We report an inverse association between Mediterranean diet and NAFLD. Mediterranean diet protected against diabetes and CVD prospectively among subjects with NAFLD.


The associations of non-essential metal mixture with fasting plasma glucose among Chinese older adults without diabetes.
The evidence about the effect of non-essential metal mixture on fasting plasma glucose (FPG) levels among older adults without diabetes is limited. This study aims to estimate the individual and joint relationship between five non-essential metals and FPG levels in Chinese older adults without diabetes. This study included 2362 older adults without diabetes. Urinary concentrations of five non-essential metals, i.e., cesium (Cs), aluminum (Al), thallium (Tl), cadmium (Cd), and arsenic (As), were detected by inductively coupled plasma mass spectrometry (ICP-MS). The associations of single metals and the metal mixture with FPG levels were assessed using linear regression and Bayesian kernel machine regression (BKMR) models, respectively. Adjusted single-metal linear regression models showed positive associations of urinary Al (β = 0.016, 95%CI: 0.001-0.030) and Cs (β = 0.018, 95%CI: 0.006-0.031) with FPG levels. When comparing the 2th, 3th, and 4th quartiles of urine Cs to its 1th quartile, the significant associations between Cs and FPG levels were found and presented as an "inverted U" trend (βQ2 vs. Q1: 0.034; βQ3 vs. Q1:0.054; βQ4 vs. Q1: 0.040; all P<0.05). BKMR analyses showed urinary level of Cs exhibited an "inverted U" shape association with FPG levels. Moreover, the FPG levels increased linearly with the raised levels of the non-essential metal mixture, and the posterior inclusion probability (PIP) of Cs was the highest (0.92). Potential positive interaction of As and Cs on FPG levels was found in BKMR model. Stratified analysis displayed significant interactions of hyperlipidemia and urine Cs or Tl on FPG levels. An inverse U-shaped association between Cs and FPG was found, individually and as mixture. The FPG levels increased with the raised levels of the non-essential metal mixture, and Cs was the most contributor to FPG levels. Further research is required to confirm the correlation between non-essential metals and FPG levels and to clarify the underlying mechanisms.


Hydroxypropyl methylcellulose-based controlled release dosage by melt extrusion and 3D printing: Structure and drug release correlation.
The objective of this study was to develop a new approach for fabrication of zero order release of active pharmaceutical ingredients (APIs) using hot-melt extrusion (HME) and 3D printing technology to generate tablets with specific 3D structures. By correlating the geometry of the 3D printed tablets with their dissolution and drug release rates, mathematical models that have been developed to describe drug release mechanisms were also studied. Acetaminophen was used as a model drug, and Benecel™ hydroxypropyl methylcellulose (HPMC) E5 and Soluplus® were used to formulate nine fuse depositional 3D-printed tablets with different inner core fill densities and outside shell thicknesses. This work reports the successful fabrication of solid-dispersion filaments with an API dispersed in HPMC based matrix via HME technology, and the production of zero order controlled release tablets with different 3D structures (tablets #3, 5, 6, and 9) using a 3D printer.


Cannabis-induced dysphoria/paranoia mediates the link between childhood trauma and psychotic-like experiences in young cannabis users.
Childhood trauma (abuse and neglect) is a major risk factor for cannabis use disorder and psychotic-spectrum disorders. Psychotic-like experiences (PLEs) in young people who use cannabis may be an early indicator of psychosis risk following cannabis use. We examined whether (i) childhood trauma moderates the association between cannabis use and PLEs, (ii) the association between childhood trauma and cannabis use is mediated by subjective effects of cannabis (euphoria and dysphoria/paranoia), and (iii) the association between childhood trauma and PLEs is also mediated by these subjective effects. Participants were 2630 cannabis users (aged 16-25) recruited online. They were asked to complete a cross-sectional survey measuring cannabis and other substance use, childhood trauma, PLEs, and the subjective effects of cannabis (euphoria and dysphoria/paranoia). A significant interaction indicated that the effect of cannabis on PLE frequency was stronger for individuals with more severe childhood trauma. Childhood trauma was also associated with greater cannabis use and PLE frequency, both of which were mediated by subjective dysphoria/paranoia when using the drug. This suggests childhood trauma is associated with greater PLEs in young people who use cannabis, which may be linked with an increased susceptibility to the dysphoric/paranoid subjective effects when using the drug. Childhood trauma should be addressed early in young people who use cannabis to mitigate the psychosis-associated harms of the drug.


Clinical characteristics of atelectatic eardrums and adhesive otitis media in children.
Atelectatic eardrum and adhesive otitis media in children are related to persistent otitis media with effusion (OME) and eustachian tube dysfunction in infancy. However, the pathogenesis of these diseases is not fully understood, and some cases even progress to pars tensa cholesteatoma. This study analyzed the clinical characteristics of children with atelectatic eardrum and adhesive otitis media to clarify associated causes of and risk factors for progression of these middle ear pathologies in children. This retroactive study included 38 ears of 31 children with atelectatic eardrums (atelectasis group), and 19 ears of 17 children with adhesive otitis media (adhesive OM group). Thirty-two contralateral non-cholesteatoma ears of 32 children with congenital cholesteatoma were also examined as a control group. Participants were aged 15 or younger. Life history (obtained via questionnaire), associated diseases, hearing acuity, aeration and development of the temporal bone were investigated. All children in the atelectasis and adhesive OM groups had a history of recurrent acute otitis media (rAOM) and/or OME. The prevalence of perennial allergic rhinitis was 18 cases (58%) in the atelectasis group and 16 cases (94%) in the adhesive OM group. The prevalence of perennial allergic rhinitis was significantly higher in the adhesive OM group compared to the control group (P < 0.01). The development of mastoid air cells, categorized by MC classification, showed MC0 + MC1 (poor pneumatization) in 19 ears (50.0%) with atelectatic eardrums and 12 ears (63.2%) with adhesive OM. Poor pneumatized mastoid was more frequently observed in the ears of the atelectasis and adhesive OM groups compared to the control group (P < 0.01). No significant difference was found in regards to aeration of the middle ear between the two groups; however, aeration was significantly poorer in both groups compared to the control group (P < 0.01). Three characteristics were analyzed using multivariate logistic regression: perennial allergic rhinitis (odds ratio [OR] 4.319, P = 0.013), poor mastoid pneumatization (OR 8.457, P = 0.012), and pars flaccida retraction pocket (OR 20.897, P = 0.006). These characteristics were shown to be significant risk factors for atelectatic eardrums and adhesive OM. In addition, the predisposition to perennial allergic rhinitis was shown to be the most important factor in the progression from atelectatic eardrum to adhesive otitis media (OR 16.615, P = 0.012). Children with perennial allergic rhinitis, poor development of mastoid air cells, poor aeration of the temporal bone, and with pars flaccida retraction pocket were at an increased risk of developing an atelectatic eardrum and adhesive OM. In particular, perennial allergic rhinitis was shown to be a significant risk factor in the progression from atelectatic eardrum to adhesive otitis media. Allergic inflammation may affect not only the nasal passages but also the eustachian tube, resulting in persistent middle ear dysfunction. Therefore, children with rAOM/OME who have these risk factors should be carefully monitored and treat over time in effort to prevent progression of pathology.


Relation of left ventricular function to habitual alcohol consumption.
Left ventricular (LV) dysfunction is a frequent finding in chronic alcoholic subjects. LV function's relation to alcohol use in the general population, where low and moderate consumption predominate, was studied in this work. A random sample of 120 people born in 1954 was invited to participate in the study, and 93 (42 men and 51 women) enrolled. Ethanol use was studied by 2-month daily recording of all alcoholic drinks; smoking and physical activity were quantified likewise, and salt intake by 7-day food records. Subsequently, subjects underwent an LV examination by M-mode echocardiography, and a transmitral flow velocity study by pulsed Doppler ultrasound. The relations of LV measurements to alcohol use were studied by multiple linear regression adjusting for sex, body size, blood pressure, heart rate, smoking, physical activity and dietary salt intake. No subject had clinical heart disease. The average daily ethanol consumption ranged from 0 to 1.2 g/kg of body weight (median 0.2). Statistically significant associations with square-root daily ethanol use were found for LV end-systolic diameter (regression coefficient [b] +/- SE 4.0 +/- 1.5 mm/square root of g/kg; p < 0.01), fractional shortening (b = -3.9 +/- 1.8%/square root of g/kg; p < 0.05), peak early transmitral velocity (b = -8.9 +/- 3.5 cm/s/square root of g/kg; p < 0.05), and peak atrial transmitral velocity (b = -4.9 +/- 1.9 cm/s/square root of g/kg; p < 0.05). No interactions with sex were observed.(ABSTRACT TRUNCATED AT 250 WORDS)


Brain modulation of the immune system: association between lymphocyte responsiveness and paw preference in mice.
An association between handedness and immune disorders has been described in man, left-handers being more susceptible to autoimmune or allergic diseases. However, this correlation was established between handedness and clinical signs of immune disorders without studying immune functions. Using an animal model, we demonstrated for the first time an association between handedness and lymphocyte reactivity. Left-handed mice were shown to exhibit higher mitogen-induced T lymphocyte proliferation than right-handed animals.


Experiences and perspectives of adults living with systemic lupus erythematosus: thematic synthesis of qualitative studies.
Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease that significantly impairs patients' quality of life and can be life threatening. This study aimed to describe the experiences and perspectives of adults living with SLE. We conducted a systematic review and thematic synthesis of qualitative studies that explored the experiences of adults living with SLE. We searched MEDLINE, Embase, PsycINFO, CINAHL (to November week 1, 2012), Google Scholar, a thesis database, and reference lists of relevant articles. Forty-six studies involving 1,385 participants were included. Five themes were identified: restricted lifestyle(including subthemes of pervasive pain, debilitating fatigue, mental deterioration, disruptive episodic symptoms, and postponing parenthood), disrupted identity (gaining diagnostic closure, prognostic uncertainty, being a burden, hopelessness, heightened self-consciousness, fearing rejection, and guilt and punishment), societal stigma and indifference(illness trivialization, socially ostracized, and averse to differential treatment), gaining resilience (optimism, control and empowerment, being informed and involved, and valuing mutual understanding), and treatment adherence (preserving health, rapport with clinicians, negotiating medication regimens, and financial burden). SLE has a severe and pervasive impact on patients' self-esteem and independence. Their physical and social functioning is limited and they feel anxious about their future. Patients perceive that SLE is trivialized, misunderstood,and stigmatized by their family, friends, and physicians, which intensifies their sense of isolation. Educational, psychosocial, and self-care interventions are needed to promote mental resilience, positive coping strategies, self-advocacy, and capacities for social participation, and thereby to achieve better treatment and health outcomes in patients with SLE.


The effect of solvent grade on thin layer chromatographic analysis of writing inks.
The effects on the separation of writing ink dyes and the repeatability of the Rf values from using different grades of chemicals used in solvent system I (SSI) and solvent system II (SSII) for thin-layer chromatographic (TLC) ink analysis were studied. Solvent system I consists of a 70:35:30 mixture of ethyl acetate, ethanol, and water. Solvent system II consists of a 50:10:15 mixture of ethanol, water, and n-butanol. Since 1991, the ASTM International Guideline E 1422 has recommended that the purity of solvents should be "reagent grade" and that water quality should be "distilled or equivalent." A total of 25 blue and 25 black inks were selected for analysis. Thirteen of each color ink were ballpoint and the remainder were non-ballpoint. The observations show that there is a solvent grade effect on both the separation and clarity of the ink dyes and the repeatability of their Rf values. These results indicate that the grades and manufacturers of solvents used in solvent systems for thin-layer chromatography must be consistent. This is especially critical for searching TLC plates against those from a large ink library in casework. Overall, the combination of solvents that produced the best results for solvent system I consisted of denatured ethanol, HPLC grade water, and ACS grade ethyl acetate. There was no consensus for the best combination of solvent grades for solvent system II; however, it was shown that different grades did have an effect on the separation of ink components.


Asymmetrically split DNAzyme-based colorimetric and electrochemical dual-modal biosensor for detection of breast cancer exosomal surface proteins.
Exosomal surface proteins are potentially useful for breast cancer diagnosis and awareness of risk. However, some detection techniques involving complex operations and expensive instrumentation are limited to advance to clinical applications. To solve this problem, we develop a dual-modal sensor combining naked-eye detection and electrochemical assay of exosomal surface proteins from breast cancer. Most of existing sensors rely on aptamers recognizing exosomes and generating amplified signals at the same time, which require well-designed aptamer probes to avoid difficulties in identifying exosomes. In our work, aptamers not bound by the exosomes can serve as complete templates to induce formation of G quadruplexes. The peroxidase activity of the G-quadruplex/hemin DNAzyme catalyze substrates can generate both color and electrochemical signals. The developed dual-modal sensor offers a remarkable capability to differentiate nonmetastatic, metastatic breast cancer patients, and healthy individuals through the analysis of exosomal surface proteins. The sensor's distinctive features, including its universality, simplicity, and cost-effectiveness, position it as a promising diagnostic tool in breast cancer research and clinical practice.