Mass action analysis of kinetics and extent of fusion between Sendai virus and phospholipid vesicles.
The kinetics and extent of fusion between Sendai virus particles and liposomes were investigated with an assay for lipid mixing based on the relief of self-quenching of fluorescence. The measurements, which were carried out at pH 7.4 and 5.0, included liposomes of three compositions, cardiolipin (CL), CL/dioleoylphosphatidylcholine (CL/DOPC 1:1), and phosphatidylserine (PS). Liposomal lipid concentrations varied from 2.5 to 50 microM. In addition, the effect of low concentrations of the dehydrating agent poly(ethylene glycol) (PEG) on fusion between the virus and the liposomes at pH 7.4 was studied. The results were analyzed in terms of a mass action kinetic model which views the overall fusion reaction as a sequence of a second-order process of virus-liposome adhesion or aggregation, followed by the first-order fusion reaction itself. The fusion products were shown to consist of a single virus particle and several liposomes. Analytical solutions were found for the final extent of fusion and increase in fluorescence intensity following the fusion of fluorescently labeled virus particles with liposomes. The final extents of fluorescence intensity were explained by assuming an essentially irreversible binding of liposomes to inactive virus particles. The percents of active virus particles and the rate constants of fusion and aggregation were larger at pH 5 than at pH 7.4, increased when PEG was included in the medium, and varied with liposomal lipid composition according to the sequence CL greater than CL/DOPC greater than PS.(ABSTRACT TRUNCATED AT 250 WORDS)


Composite polymer electrolyte containing ionic liquid and functionalized polyhedral oligomeric silsesquioxanes for anhydrous PEM applications.
A new type of supported liquid membrane was made by combining an ionic liquid (IL) with a Nafion membrane reinforced with multifunctional polyhedral oligomeric silsesquioxanes (POSSs) using a layer-by-layer strategy for anhydrous proton-exchange membrane (PEM) application. The POSS was functionalized by direct sulfonation, and the sulfonated POSS (S-POSS) was incorporated into Nafion 117 membranes by the infiltration method. The resultant hybrid membrane shows strong ionic interaction between the Nafion matrix and the multifunctional POSS, resulting in increased glass transition temperature and thermal stability at very low loadings of S-POSS (1%). The presence of S-POSS has also improved the proton conductivity especially at low humidities, where it shows a marked increase due to its confinement in the ionic domains and promotes water uptake by capillary condensation. In order to achieve anhydrous conductivity, the IL 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide (BMI-BTSI) was incorporated into these membranes to provide proton conduction in the absence of water. Although the incorporation of an IL shows a plasticizing effect on the Nafion membrane, the S-POSS composite membrane with an IL shows a higher modulus at high temperatures compared to Nafion 117 and a Nafion-IL membrane, with significantly higher proton conductivity (5 mS/cm at 150 degrees C with 20% IL). This shows the ability of the multifunctional POSS and IL to work symbiotically to achieve the desirable proton conductivity and mechanical properties of such membranes by enhancing the ionic interaction within the material.


[Chronic complications of sickle cell disease].
Chronic complications of sickle cell disease take an increasing role in the management of patients due to their morbidity and mortality impact. The prevalence of chronic organ damages increases as the age of patients followed in France. Few organs seem unaffected by the disease. The natural history of chronic complication is highly variable from one patient to another, and the distribution of those manifestations throughout life, is different depending on their nature and pathophysiology. Thus we can, for example, distinguish SS patients presenting a "hyperhemolytic" phenotype associated with dense red blood cells that have a high risk of vascular complications including kidney disease, pulmonary hypertension, leg ulcers and priapism, from SC patients with high hemoglobin levels, who have a higher risk of retinopathy, osteonecrosis and sensory syndrome, probably related to hyperviscosity. Dependent on the age, we could also oppose cerebral vasculopathy responsible of ischemic stroke since childhood, and kidney damage which effects are visible more gradually with aging. Sickle cell disease is one of the most systemic pathologies contrasting with its monogenic characteristic and its inter- and intra-individual variability. A better understanding of pathophysiological mechanisms responsible for those complications is necessary to develop new preventive and therapeutic approaches.


Anti-apoptotic role of Sonic hedgehog protein at the early stages of nervous system organogenesis.
In vertebrates the neural tube, like most of the embryonic organs, shows discreet areas of programmed cell death at several stages during development. In the chick embryo, cell death is dramatically increased in the developing nervous system and other tissues when the midline cells, notochord and floor plate, are prevented from forming by excision of the axial-paraxial hinge (APH), i.e. caudal Hensen's node and rostral primitive streak, at the 6-somite stage ( Charrier, J. B., Teillet, M.-A., Lapointe, F. and Le Douarin, N. M. (1999). Development 126, 4771-4783). In this paper we demonstrate that one day after APH excision, when dramatic apoptosis is already present in the neural tube, the latter can be rescued from death by grafting a notochord or a floor plate fragment in its vicinity. The neural tube can also be recovered by transplanting it into a stage-matched chick embryo having one of these structures. In addition, cells engineered to produce Sonic hedgehog protein (SHH) can mimic the effect of the notochord and floor plate cells in in situ grafts and transplantation experiments. SHH can thus counteract a built-in cell death program and thereby contribute to organ morphogenesis, in particular in the central nervous system.


Thyroid hormone and the brain: Mechanisms of action in development and role in protection and promotion of recovery after brain injury.
Thyroid hormone (TH) is essential for normal brain development and may also promote recovery and neuronal regeneration after brain injury. TH acts predominantly through the nuclear receptors, TH receptor alpha (THRA) and beta (THRB). Additional factors that impact TH action in the brain include metabolism, activation of thyroxine (T4) to triiodothyronine (T3) by the enzyme 5'-deiodinase Type 2 (Dio2), inactivation by the enzyme 5-deiodinase Type 3 (Dio3) to reverse T3 (rT3), which occurs in glial cells, and uptake by the Mct8 transporter in neurons. Traumatic brain injury (TBI) is associated with inflammation, metabolic alterations and neural death. In clinical studies, central hypothyroidism, due to hypothalamic and pituitary dysfunction, has been found in some individuals after brain injury. TH has been shown, in animal models, to be protective for the damage incurred from brain injury and may have a role to limit injury and promote recovery. Although clinical trials have not yet been reported, findings from in vitro and in vivo models inform potential treatment strategies utilizing TH for protection and promotion of recovery after brain injury.


Riboflavin immobilized Fe3O4 magnetic nanoparticles carried with n-butylidenephthalide as targeting-based anticancer agents.
n-Butylidenephthalide (BP) is a potential anti-cancer drug, which can be extracted from Angelica sinensis (Danggui). Previous reports have shown the effectiveness of BP in treating cancer diseases. However, BP has no targeting capacity towards specific cancer cells. To improve treatment efficiency and reduce the dose of BP used in cancer treatment, targeting-based approaches should be developed. In the present study, we used riboflavin-5'-phosphate (RFMP) immobilized iron oxide magnetic nanoparticles (Fe3O4 MNPs) as carriers for BP to treat cancer cell lines derived from liver, prostate and breast. These model cancer cells overexpress riboflavin receptors on their cell membrane and are also sensitive to BP treatment. Thus, BP-binding free RFMP on MNPs can be used as probes to target these model cells, whereas BP can be readily released on target cancer cells. Cell viability was twofold lower by using Fe3O4@RFMP MNPs immobilized with BP than that achieved by using free-form BP at a similar amount. Moreover, BP-Fe3O4@RFMP MNPs have no apparent harmful effects on non-target cells. In addition, we evaluated the level of cysteine-aspartic acid protease 3 (caspase 3) in the resultant cell lysate obtained after treatment by BP-Fe3O4@RFMP MNPs to demonstrate that apoptosis is mainly involved in the growth inhibition of target cells.


[Current status and future directions of ATL].
Patients with adult T-cell leukemia/lymphoma (ATL), which is caused by human T-cell lymphotropic virus type 1, exhibit an extremely poor prognosis. ATL was first reported in 1977 in Japan as a distinct T-cell neoplasm, and its basic and clinical research have been led by Japanese investigators. This study aims to review the scenario since the discovery of ATL/HTLV-1 to the current status of ATL research and medicine and to consider its future directions.


Coherent and incoherent charge transport in linear triple quantum dots.
One of the fundamental questions in quantum transport is how charge transfer through complex nanostructures is influenced by quantum coherence. We address this issue for linear triple quantum dots by comparing a Lindblad density matrix description with a Pauli rate equation approach and analyze the corresponding zero-frequency counting statistics of charge transfer. The impact of decaying coherences of the density matrix due to dephasing is also studied. Our findings reveal that the sensitivity to coherence shown by shot noise and skewness, in particular in the limit of large coupling to the drain reservoir, can be used to unambiguously evidence coherent processes involved in charge transport across triple quantum dots. Our analytical results are obtained by using the characteristic polynomial approach to full counting statistics.


Fulminant Stenotrophomonas maltophilia soft tissue infection in immunocompromised patients: an outbreak transmitted via tap water.
Soft tissue infection caused by Stenotrophomonas maltophilia is uncommon, but nosocomial infections had been reported. We describe herein 2 young female patients, with severe neutropenia, on broad spectrum antimicrobial agents for neutropenic fever, with Hickman-type central venous catheter, who developed mucocutaneous and soft tissue infections with rapidly progressive and devastating course. Cultures from the skin of both patients and from blood of one of them grew S. maltophilia. Both patients died and post mortem examination of the patient with S. maltophilia bacteremia revealed extensive soft tissue necrosis and a vegetation on the mitral valve that grew S. maltophilia. The infection occurred in both patients at the same time and in the same ward. Epidemiological study was done, and surveillance cultures grew the organism from the faucets from the room of 1 patient and also from some of the neighboring rooms in our ward but not from any other ward nor in the water reservoir of the building.


Development of a cancer DNA phenotype prior to tumor formation.
Using the carcinogen 3-methylcholanthrene (MCA), we demonstrate with Fourier transform-infrared spectroscopy that a cancer DNA phenotype is produced well in advance of palpable tumors. We further demonstrate that the administration of cyclophosphamide markedly inhibits the development of the cancer phenotype and concomitantly delays tumor formation. MCA, injected into the hind legs of mice, produced a variety of significant structural changes in the nucleotide bases and phosphodiester-deoxyribose backbone, as reflected in a substantial (34%) difference between the mean DNA spectra of the control and the MCA-injected mice. Strikingly, 57 days before the mean appearance of tumors, we could not distinguish the DNA structure of the histologically normal tissues of the MCA-injected mice from the DNA structure of the tumor tissues. This finding indicates the early development of a cancer phenotype. Confirmatory evidence was obtained when tissues from a group of mice injected with both MCA and cyclophosphamide did not manifest the cancer phenotype, and their mean DNA structure closely resembled that of the control mice. Accordingly, we propose that the cancer DNA phenotype, as evinced by Fourier transform-infrared spectroscopy, is a promising early indicator of tumor formation, and we postulate that agents capable of inhibiting this phenotype may delay or prevent carcinogenesis.


Herpes simplex virus type 1 is the prevailing cause of genital herpes in the Tel Aviv area, Israel.
The changing epidemiology of genital herpes with the increasing importance of herpes simplex virus (HSV) type 1 prompted a study on the relative prevalence of HSV-1 and HSV-2 among cases of genital herpes in the Tel Aviv area, Israel. A retrospective laboratory-based study of positive genital and nongenital herpes cultures performed at the Beilinson Medical Center between 1993 and 2002. Data regarding the number of isolates of each type and the age and sex of patients with genital lesions were retrieved from the database. Cultures were performed using Vero cells, and positive results were confirmed and typed by immunofluorescence. A total of 285 positive genital cultures and 659 positive nongenital cultures were recorded. HSV-1 was identified in 189 (66.3%) of the positive genital specimens and in 656 (99.55%) of the nongenital specimens. HSV-1 was isolated in 174 of 262 (66.4%) female subjects and 15 of 23 (65.2%) male subjects. The proportion of HSV-1 genital isolates was 72.7% in patients 15 to 24 years of age, 62% in those 25 to 44 years, and 46% in those aged 45 years or older. Overall, the annual isolation rate of genital HSV-1 has not changed markedly over the years. Herpes simplex virus type 1 has clearly been the predominant HSV type isolated from genital specimens in the Tel Aviv area over the last decade.


Defining Treatment Success After 2-Stage Exchange Arthroplasty for Periprosthetic Joint Infection.
Two-stage exchange arthroplasty remains the preferred surgical treatment method for patients with chronic periprosthetic joint infection (PJI). The success of this procedure is not known exactly as various definitions of success have been used. This study aimed at analyzing the difference in outcome following 2-stage exchange arthroplasty using different definitions for success. A retrospective study of 703 patients with PJI who underwent resection arthroplasty and spacer insertion between January 1999 and June 2015 was performed. Chart review identified intraoperative cultures at the time of spacer, reimplantation, and any subsequent reinfections or surgeries following spacer insertion. After applying the exclusion criteria, a total of 570 patients were included in the analysis. Five definitions of treatment success were assessed: (1) Delphi consensus success, (2) modified Delphi consensus success, (3) microbiological success, (4) implant success, and (5) surgical success. Of the 570 patients with PJIs, 458 were reimplanted at a mean of 4.1 months. Mortality was 13.9% with 6.7% occurring before reimplantation. Treatment success was highly variable depending on the definition used (54.2%-88.9%). In 19.6% of PJI cases, the Delphi consensus definition could not be assessed as reimplantation never occurred. Furthermore, 67.0% of these patients underwent reoperations, which may not be accounted for in the Delphi consensus definition. Treatment success rates vary dramatically depending on the definition used at our institution. We hope these definitions can help bring forth awareness for standardized reporting of outcomes, but further validation and agreement of these definitions among surgeons and infectious disease physicians is crucial.


Spatial and temporal evolution of urban carbon emission efficiency in China.
Improving carbon emission efficiency is crucial for achieving carbon peak and carbon neutrality. This paper analyzes the carbon emission efficiency of Chinese cities using panel data from 275 prefecture-level cities between 2006 and 2020. The super-efficiency SBM (undesirable slacks-based measurement) model of undesired output, combined with kernel density estimation and exploratory data analysis, is employed. This study finds, firstly, from 2006 to 2020, the average efficiency of carbon emissions in Chinese cities declined from 0.53 to 0.48, indicating a downward trend. Secondly, from a temporal perspective, the level of dispersion in urban carbon emission efficiency has become increasingly distinct over time, coupled with a decrease in polarization. Thirdly, in terms of spatial analysis, urban carbon emission efficiency in China shows a positive correlation in a global context. In terms of local spatial correlation, it primarily exhibits high-high and low-low clusters, with a few instances of low-high and high-low clusters. Finally, based on the research findings, this paper proposes suggestions to improve urban carbon emission efficiency.


Cancer issues.
The potential for hormone therapy to cause cancer is the greatest fear for postmenopausal women considering hormone replacement therapy (HRT). Breast cancer is the most common female malignancy, for which HRT is one of many modifiable risk factors, often attracting disproportionate attention. Randomized controlled trials have confirmed that in postmenopausal women aged 50-59 years taking combined oestrogen and progestogen HRT over 5 years, there will be three extra cases of breast cancer per 1000 women. With the use of unopposed conjugated equine oestrogens, there would be four fewer cases over the same time. Women can be advised that the risk of breast cancer is not significantly increased with up to 3 years of combined HRT and up to 5 years of unopposed oestrogen. Unopposed oestrogen increases the risk of endometrial hyperplasia and carcinoma significantly, and this is dose and duration dependent. The addition of progestogen prevents the proliferative effect of oestrogen on the endometrium, and may even reduce the risk of endometrial cancer compared with non-users if given continuously. The use of combined oral contraception in premenopausal women also reduces the risk of endometrial cancer but increases the risk of cervical carcinoma significantly. HRT does not influence the risk of cervical cancer. Epithelial ovarian cancer risk may be slightly increased with long-term use of unopposed oestrogen, is not altered by the addition of progestogen, and is reduced significantly in users of combined oral contraception. The mechanism for these effects is not understood. Colorectal cancer and possibly lung and gastric cancers are reduced by the use of HRT. Apart from a slight increased risk of gallbladder disease and carcinoma with HRT, there are no data linking oestrogen or progestogen with any other malignancies.


Cognitive therapy versus exposure therapy for hypochondriasis (health anxiety): A randomized controlled trial.
Cognitive-behavioral therapy has proven to be highly effective in the treatment of hypochondriasis and health anxiety. However, little is known about which therapeutic interventions are most promising. The aim of the present study was to compare the efficacy of cognitive therapy (CT) with exposure therapy (ET). Eighty-four patients with a diagnosis of hypochondriasis were randomly allocated to CT, ET, or a waiting list (WL) control group. The primary outcome measure was a standardized interview that evaluated hypochondriacal cognitions as well as behaviors conducted by independent diagnosticians. Several self-report questionnaires were evaluated as secondary outcome measures. Treatment success was evaluated at posttreatment and at 1-year follow-up. Both CT (Hedges's g = 1.01-1.11) and ET (Hedges's g = 1.21-1.24) demonstrated their efficacy in comparison with the WL in the primary outcome measure. Moreover, a significant reduction in depressive symptoms and bodily complaints was found in the secondary outcome measures for both treatments in comparison with the WL, but anxiety symptoms were only significantly reduced by ET. In a direct comparison, no significant differences were found between CT and ET in the primary or the secondary outcome measures. Regarding safety behaviors, we found a significantly larger improvement with ET than with CT in the completer analyses. The results suggest high efficacy of CT as well as ET in the treatment of hypochondriasis. Cognitive interventions were not a necessary condition for the change of dysfunctional cognitions. These findings are relevant to the conceptualization and psychotherapeutic treatment of hypochondriasis and health anxiety.


Prevalence and risk factors associated with the formation of dermal lesions on the foot during hiking.
The aim of this study is to assess the prevalence of blisters on the foot during hiking and the factors associated with this condition. A cross-sectional observational comparative study was conducted of 315 patients treated at two hostels, located on the Way of Saint James, in northern Spain. The study participants were interviewed and clinically examined to obtain sociodemographic and clinical variables. The variables recorded concerned the type of terrain covered (asphalt or dirt trails), the weight carried (backpack), the footwear used (weight, type, impermeability), the type of socks worn and the hydration of the skin obtained. The inclusion criteria were at least 18 years and to walk at least 20 km in the last five days. 74% (n = 233) of the hikers presented a bullous lesion on the foot after completing several stages of hiking. The most frequent locations were the first or second metatarsal head and the fifth toe. Logistic regression showed that risk factors for the appearance of blistering were the number of kilometres walked on asphalt (p = .001 [95% CI (1.019-1.064)]) and having wet socks at the end of the day (p = . 006 [95% CI (1.286-4.479)]). The protective factors identified were walking on a dirt, grass or gravel surface (p < .001 [95% CI (0.982- 0.995)]) and using customised plantar orthoses (p = .001 [95% CI (0.085) - 0.512)]). The type of terrain is a determining factor in the appearance of blisters. Walking on a dirt trail reduces the risk. Using custom made insoles and controlling humidity are other factors that should be considered as preventive measures.


Mason-Pfizer virus characterization: a similar virus in a human amniotic cell line.
Mason-Pfizer monkey virus (MP-MV) is a RNA virus with an RNA-instructed DNA polymerase first isolated from a rhesus monkey mammary adenocarcinoma in 1970. Until recently, there have been no other isolates. A continuous human amnion cell line, AO, was found to be producing a virus indistinguishable or closely related to the Mason-Pfizer virus as measured by morphological, immunological, and biochemical methods. By thin-section electron microscopy, the extracellular virus particle in AO line is 115 to 130 nm in diameter and has a preformed nucleoid (80 to 90 nm) before budding, properties which are also characteristic of MP-MV. Two proteins of the virus from the AO line were studied. By immunodiffusion, sera which react specifically with MP-MV give a line of identity with virus from the AO line. The AO viral RNA-instructed DNA polymerase purified by phosphocellulose chromatography was specifically inhibited by anti-MP-MV polymerase sera, and the AO cells contained both DNA and RNA sequences related to MP-MV (3)H-DNA. Viruses thus far indistinguishable from MP-MV have also recently been found by others in different human lines, raising again the question of the species of origin of MP-MV. Because the virus in the AO cells cannot be differentiated from MP-MV, we attempted to determine the origin of MP-MV virus by measuring DNA sequences related to MP-MV (3)H-DNA in uninfected human and rhesus monkey cells. The quantity of MP-MV-like DNA sequences in uninfected primate tissues was found to be much lower than the amount of DNA sequences of murine type-B or type-C viruses in uninfected murine tissues. Thus, it was not possible to determine whether the virus produced by AO cells or MP-MV was of human or monkey origin, or both.


The KSR2-rs7973260 Polymorphism is Associated with Metabolic Phenotypes, but Not Psychological Phenotypes, in Chinese Elders.
To examine the associations between genetic variants of KSR2 (kinase suppressor of RAS)-rs7973260, RAPGEF6 (guanine nucleotide exchange factor 6)-rs3756290, LOC105377703-rs4481363, and subjective well-being (SWB) and depressive symptoms (DSs) in Chinese elders, which were recently associated in a genome-wide association study conducted in Caucasians. The pleiotropic effects of KSR2-rs7973260 on metabolic phenotypes were also explored. We used data from 1788 older individuals aged 70-84 years from the aging arm of the Rugao Longevity and Aging Study, a population-based cohort study conducted in the Jiangsu province of China. No significant distributions of genotype frequencies were observed between life-satisfied and -unsatisfied groups across those with the three polymorphisms. The level of SWB components (positive affect, negative affect, and affect balance) and DSs did not differ among genotypes of the three variants. However, the presence of GA+AA of KSR2-rs7973260 was significantly higher in the metabolic syndrome (MetS), severe hypertriglyceridemia (HTG), and diabetes groups than in control groups (43.7% vs. 37.6%, 46.4% vs. 37.6%, 45.8% vs. 37.9%, respectively). The A allele of rs7973260 was associated with increased risk of MetS, severe HTG, and diabetes with an odds ratios (95% confidence intervals) of 1.289 (1.002-1.658), 1.438 (1.076-1.921), and 1.384 (1.022-1.875), which remained significant after multiple adjustments. Rs7973260, rs3756290, and rs4481363 were not associated with SWB and DSs in Chinese elders. However, the KSR2-rs7973260 A allele exhibited pleiotropic effects on some metabolic phenotypes in Chinese elders. These effects should be validated in future studies.


The relationship between ACE/AGT gene polymorphisms and the risk of diabetic retinopathy in Chinese patients with type 2 diabetes.
This study aims to investigate the association between renin-angiotensin system gene polymorphism and diabetic retinopathy (DR) in Chinese patients with type 2 diabetes. We consecutively included 1491 patients for the assessment of ACE I/D and AGT M/T gene polymorphisms in 345 DR cases and 1146 patients without retinopathy (DNR). Albuminuria was defined by urine albumin creatinine ratio and albumin excretion rate. Compared with the NDR patients, the DR cases displayed a higher proportion of diabetic nephropathy (32.68% vs. 6.52%, χ2 = 150.713, p < 0.001). The DR cases and DNR individuals did not differ in the frequency of genotypes and alleles of ACE I/D and AGT M/T (all p > 0.05). Intriguingly, DR patients with obesity showed higher frequency of DD (χ2 = 4.181, p = 0.041), but no significant difference exists in the other stratified BMI and hypertension analyses (all p > 0.05). Binary logistic regression displays that the association of the ACE and AGT gene polymorphisms in DR patients is not significant after adjusting for confounding covariates in all the comparisons. The ACE and AGT gene polymorphisms are not associated with the progress of diabetes developing into retinopathy in Chinese patients with type 2 diabetes. However, more investigations are needed to further prove the association.


Enhanced Switching Reliability of Hf0.5Zr0.5O2 Ferroelectric Films Induced by Interface Engineering.
Ferroelectric materials have been widely researched for applications in memory and energy storage. Among these materials and benefiting from their excellent chemical compatibility with complementary metal-oxide-semiconductor (CMOS) devices, hafnia-based ferroelectric thin films hold great promise for highly scaled semiconductor memories, including nonvolatile ferroelectric capacitors and transistors. However, variation in the switched polarization of this material during field cycling and a limited understanding of the responsible mechanisms have impeded their implementation in technology. Here, we show that ferroelectric Hf0.5Zr0.5O2 (HZO) capacitors that are nearly free of polarization "wake-up"─a gradual increase in switched polarization as a function of the number of switching cycles─can be achieved by introducing ultrathin HfO2 buffer layers at the HZO/electrodes interface. High-resolution transmission electron microscopy (HRTEM) reveals crystallite sizes substantially greater than the film thickness for the buffer layer capacitors, indicating that the presence of the buffer layers influences the crystallization of the film (e.g., a lower ratio of nucleation rate to growth rate) during postdeposition annealing. This evidently promotes the formation of a polar orthorhombic (O) phase in the as-fabricated buffer layer samples. Synchrotron X-ray diffraction (XRD) reveals the conversion of the nonpolar tetragonal (T) phase to the polar orthorhombic (O) phase during electric field cycling in the control (no buffer) devices, consistent with the polarization wake-up observed for these capacitors. The extent of T-O transformation in the nonbuffer samples is directly dependent on the duration over which the field is applied. These results provide insight into the role of the HZO/electrodes interface in the performance of hafnia-based ferroelectrics and the mechanisms driving the polarization wake-up effect.


Genera of Mythicomyiidae (Insecta, Diptera) new to the fauna of Morocco, with descriptions of new species.
Three genera of Mythicomyiidae are newly recorded from Morocco: Glabellula, Mythenteles, and Leylaiya. A total of 8 species of Mythicomyiidae are currently known from the country; of those, 3 new species are described and illustrated: Glabellula maroccana Evenhuis Kettani, n. sp.; Mythenteles signifera Evenhuis Kettani, n. sp. and Leylaiya pellea Evenhuis Kettani, n. sp. A key to the genera of Mythicomyiidae in Morocco is presented.


Oxymetazoline inhibits proinflammatory reactions: effect on arachidonic acid-derived metabolites.
The nasal decongestant oxymetazoline effectively reduces rhinitis symptoms. We hypothesized that oxymetazoline affects arachidonic acid-derived metabolites concerning inflammatory and oxidative stress-dependent reactions. The ability of oxymetazoline to model pro- and anti-inflammatory and oxidative stress responses was evaluated in cell-free systems, including 5-lipoxygenase (5-LO) as proinflammatory, 15-lipoxygenase (15-LO) as anti-inflammatory enzymes, and oxidation of methionine by agglomerates of ultrafine carbon particles (UCPs), indicating oxidative stress. In a cellular approach using canine alveolar macrophages (AMs), the impact of oxymetazoline on phospholipase A(2) (PLA(2)) activity, respiratory burst and synthesis of prostaglandin E(2) (PGE(2)), 15(S)-hydroxy-eicosatetraenoic acid (15-HETE), leukotriene B(4) (LTB(4)), and 8-isoprostane was measured in the absence and presence of UCP or opsonized zymosan as particulate stimulants. In cell-free systems, oxymetazoline (0.4-1 mM) inhibited 5-LO but not 15-LO activity and did not alter UCP-induced oxidation of methionine. In AMs, oxymetazoline induced PLA(2) activity and 15-HETE at 1 mM, enhanced PGE(2) at 0.1 mM, strongly inhibited LTB(4) and respiratory burst at 0.4/0.1 mM (p < 0.05), but did not affect 8-isoprostane formation. In contrast, oxymetazoline did not alter UCP-induced PLA(2) activity and PGE(2) and 15-HETE formation in AMs but inhibited UCP-induced LTB(4) formation and respiratory burst at 0.1 mM and 8-isoprostane formation at 0.001 mM (p < 0.05). In opsonized zymosan-stimulated AMs, oxymetazoline inhibited LTB(4) formation and respiratory burst at 0.1 mM (p < 0.05). In conclusion, in canine AMs, oxymetazoline suppressed proinflammatory reactions including 5-LO activity, LTB(4) formation, and respiratory burst and prevented particle-induced oxidative stress, whereas PLA(2) activity and synthesis of immune-modulating PGE(2) and 15-HETE were not affected.


Back to work.
Ryan Brannan, new commissioner of the Texas Division of Workers' Compensation, plans to build on the efficiencies created by earlier workers' compensation system reforms, recognizing that one of the best ways to get injured employees back to work is to "get physicians active and involved."


Comparative proteomic analysis of Streptomyces lividans Wild-Type and ppk mutant strains reveals the importance of storage lipids for antibiotic biosynthesis.
Streptomyces lividans TK24 is a strain that naturally produces antibiotics at low levels, but dramatic overproduction of antibiotics occurs upon interruption of the ppk gene. However, the role of the Ppk enzyme in relation to the regulation of antibiotic biosynthesis remains poorly understood. In order to gain a better understanding of the phenotype of the ppk mutant, the proteomes of the wild-type (wt) and ppk mutant strains, grown for 96 h on R2YE medium limited in phosphate, were analyzed. Intracellular proteins were separated on two-dimensional (2D) gels, spots were quantified, and those showing a 3-fold variation or more were identified by mass spectrometry. The expression of 12 proteins increased and that of 29 decreased in the ppk mutant strain. Our results suggested that storage lipid degradation rather than hexose catabolism was taking place in the mutant. In order to validate this hypothesis, the triacylglycerol contents of the wt and ppk mutant strains of S. lividans as well as that of Streptomyces coelicolor M145, a strain that produces antibiotics at high levels and is closely related to S. lividans, were assessed using electron microscopy and thin-layer chromatography. These studies highlighted the large difference in triacylglycerol contents of the three strains and confirmed the hypothetical link between storage lipid metabolism and antibiotic biosynthesis in Streptomyces.


Tailor-made polyelectrolyte microcapsules: from multilayers to smart containers.
This review addresses the fabrication and properties of novel polyelectrolyte microcapsules, with an emphasis on their mechanical and permeability properties. Ease of preparation through layer-by-layer self assembly, accurate control over wall thickness as well as flexibility in the choice of constituents make these capsules very promising for numerous applications in materials and life science. Moreover, by engineering the inner and outer interfaces, these capsules can be used as microreactors for precipitation, crystallization, and polymerization reactions, as well as enzymatic, and heterogeneous catalysis.


Results of Physiotherapy Treatments in Exacerbations of Chronic Obstructive Pulmonary Disease: A Systematic Review.
Purpose: The objective of this study was to review clinical trials of the effectiveness of physiotherapy compared with standard care, focused mainly on the functional status of patients hospitalized for acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Methods: Search strategies were developed for each of the databases (PubMed, Scopus, and Web of Science). The study eligibility criteria were as follows: (1) The objective was to assess the effect and efficacy of physiotherapy compared with standard care (which included only medical and pharmacological treatment); (2) adults subjects had AECOPD; (3) one of the outcome measures was functional status, defined as an individual's ability to perform the normal daily activities required to meet basic needs, fulfill usual roles, and maintain health and well-being; (4) it was a clinical trial; (5) it was written in English; (6) it was published between January 2009 and February 2016; and (7) the full-text article was available. Results: The review revealed that for patients hospitalized for AECOPD, exercise, neuromuscular electrical stimulation, breathing exercises, and chest therapy significantly improved their functional status compared with standard care. Conclusions: A variety of physiotherapy modalities have been shown to improve functional status compared with standard care among patients hospitalized for AECOPD; other outcome measures also showed improvements.


Is There a Difference in Screw Accuracy, Robot Time Per Screw, Robot Abandonment, and Radiation Exposure Between the Mazor X and the Renaissance? A Propensity-Matched Analysis of 1179 Robot-Assisted Screws.
Prospective single-cohort analysis. To compare the outcomes/complications of 2 robotic systems for spine surgery. Adult patients (≥18-years-old) who underwent robot-assisted spine surgery from 2016-2019 were assessed. A propensity score matching (PSM) algorithm was used to match Mazor X to Renaissance cases. Preoperative CT scan for planning and an intraoperative O-arm for screw evaluation were preformed. Outcomes included screw accuracy, robot time/screw, robot abandonment, and radiation. Screw accuracy was measured using Vitrea Core software by 2 orthopedic surgeons. Screw breach was measured according to the Gertzbein/Robbins classification. After PSA, a total of 65 patients (Renaissance: 22 vs. X: 43) were included. Patient/operative factors were similar between robot systems (P > .05). The pedicle screw accuracy was similar between robots (Renaissance: 1.1%% vs. X: 1.3%, P = .786); however, the S2AI screw breach rate was significantly lower for the X (Renaissance: 9.5% vs. X: 1.2%, P = .025). Robot time per screw was not statistically different (Renaissance: 4.6 minutes vs. X: 3.9 minutes, P = .246). The X was more reliable with an abandonment rate of 2.3% vs. Renaissance:22.7%, P = .007. Radiation exposure were not different between robot systems. Non-robot related complications including dural tear, loss of motor/sensory function, and blood transfusion were similar between robot systems. This is the first comparative analyses of screw accuracy, robot time/screw, robot abandonment, and radiation exposure between the Mazor X and Renaissance systems. There are substantial improvements in the X robot, particularly in the perioperative planning processes, which likely contribute to the X's superiority in S2AI screw accuracy by nearly 8-fold and robot reliability by nearly 10-fold.


Decline of heterozygosity in a large but isolated population: a 45-year examination of moose genetic diversity on Isle Royale.
Wildlife conservation and management approaches typically focus on demographic measurements to assess population viability over both short and long periods. However, genetic diversity is an important predictor of long term population vitality. We investigated the pattern of change in genetic diversity in a large and likely isolated moose (Alces alces) population on Isle Royale (Lake Superior) from 1960-2005. We characterized samples, partitioned into five different 5-year periods, using nine microsatellite loci and a portion of the mtDNA control region. We also simulated the moose population to generate a theoretical backdrop of genetic diversity change. In the empirical data, we found that the number of alleles was consistently low and that observed heterozygosity notably declined from 1960 to 2005 (p = 0.08, R2 = 0.70). Furthermore, inbreeding coefficients approximately doubled from 0.08 in 1960-65 to 0.16 in 2000-05. Finally, we found that the empirical rate of observed heterozygosity decline was faster than the rate of observed heterozygosity loss in our simulations. Combined, these data suggest that genetic drift and inbreeding occurred in the Isle Royale moose populations over the study period, leading to significant losses in heterozygosity. Although inbreeding can be mitigated by migration, we found no evidence to support the occurrence of recent migrants into the population using analysis of our mtDNA haplotypes nor microsatellite data. Therefore, the Isle Royale moose population illustrates that even large populations are subjected to inbreeding in the absence of migration.


Individualized prediction of perineural invasion in colorectal cancer: development and validation of a radiomics prediction model.
To develop and validate a radiomics prediction model for individualized prediction of perineural invasion (PNI) in colorectal cancer (CRC). After computed tomography (CT) radiomics features extraction, a radiomics signature was constructed in derivation cohort (346 CRC patients). A prediction model was developed to integrate the radiomics signature and clinical candidate predictors [age, sex, tumor location, and carcinoembryonic antigen (CEA) level]. Apparent prediction performance was assessed. After internal validation, independent temporal validation (separate from the cohort used to build the model) was then conducted in 217 CRC patients. The final model was converted to an easy-to-use nomogram. The developed radiomics nomogram that integrated the radiomics signature and CEA level showed good calibration and discrimination performance [Harrell's concordance index (c-index): 0.817; 95% confidence interval (95% CI): 0.811-0.823]. Application of the nomogram in validation cohort gave a comparable calibration and discrimination (c-index: 0.803; 95% CI: 0.794-0.812). Integrating the radiomics signature and CEA level into a radiomics prediction model enables easy and effective risk assessment of PNI in CRC. This stratification of patients according to their PNI status may provide a basis for individualized auxiliary treatment.


Modeling long-term transfers of radiocesium in farmland under different tillage and cover crop treatments.
The 2011 nuclear accident at Japan's Fukushima Daiichi Nuclear Power Plant (FDNPP) prompted inquiries about the long-term transfer of Cesium-137 (137Cs) from soil to agricultural plants. In this context, numerical modeling is particularly useful for the long-term evaluation of the consequences of agroecosystem contamination. Agricultural practices, such as tillage and cover cropping, play key roles in 137Cs recycling in agroecosystems. In this study, we used 10-year monitoring data to develop a dynamic model to predict 137Cs redistribution (via uptake, litterfall, translocation, and percolation) under different tillage (no-tillage, NT; rotary cultivation, RC; moldboard plow, MP) and cover crop (rye; hairy vetch; fallow weed) treatments. The verification exercise and assessment results indicated the model's reliability, as the temporal dynamics of predicted values agreed with observed values. Tillage significantly influenced the 137Cs distribution in soil, thereby decreasing plant uptake of 137Cs, whereas cover crop exerted a minimal effect on 137Cs cycling. Furthermore, while the 137Cs concentrations in soybean grain under RC and NT treatments were comparable 62 years after the FDNPP accident, the concentration under MP treatment remained consistently the lowest. Despite natural decay being the main cause of the decreased global 137Cs level in the agroecosystem, with minimal losses from percolation to deeper soil layers and soybean harvesting, adopting an appropriate tillage practice was shown to promote a long-term reduction of 137Cs concentration in crops. Finally, to improve the model's accuracy, further research should consider incorporating the effects of soil properties and extreme weather events on 137Cs flow into the model, as these factors are essential for realizing improved agroecosystem predictions.


Adding apples and oranges: alignment of semantic and formal knowledge.
We show that the same mechanism that mediates analogical reasoning (i.e., structural alignment) leads to interpretive "content effects" in reasoning about arithmetic word problems. Specifically, we show that both college students and textbook writers tend to construct arithmetic word problems that maintain systematic correspondence between the semantic relations that people infer from pairs of real-world objects (e.g., apples and baskets support the semantic relation CONTAIN [content, container]) and mathematical relations between arguments of arithmetic operations (e.g., DIVIDE [dividend, divisor]). Such relational alignments, to which we refer here as semantic alignments, lead to selective and sensible application of abstract formal knowledge. For example, people usually divide apples among baskets rather than baskets among apples, and readily add apples and oranges but refrain from adding apples and baskets.


Energy-density enhancement of carbon-nanotube-based supercapacitors with redox couple in organic electrolyte.
We demonstrate for the first time that the incorporation of a redox-active molecule in an organic electrolyte can increase the cell voltage of a supercapacitor. The redox molecule also contributes to increasing the cell capacitance by a faradaic redox reaction, and therefore the energy density of the supercapacitor can be significantly increased. More specifically, the addition of redox-active decamethylferrocene in an organic electrolyte results in an approximately 27-fold increase in the energy density of carbon-nanotube-based supercapacitors. The resulting high energy density (36.8 Wh/kg) stems from the increased cell voltage (1.1 V→2.1 V) and cell capacitance (8.3 F/g→61.3 F/g) resulting from decamethylferrocene addition. We found that the voltage increase is associated with the potential of the redox species relative to the electrochemical stability window of the supporting electrolyte. These results will be useful in identifying new electrolytes for high-energy-density supercapacitors.


Comparison of the effect of lignocaine instilled through the endotracheal tube and intravenous lignocaine on the extubation response in patients undergoing craniotomy with skull pins: A randomized double blind clinical trial.
A desirable combination of smooth extubation and an awake patient after neurosurgical procedures is difficult to achieve in patients with skull pins. Lignocaine instilled into endotracheal tube has been reported to suppress cough by a local mucosal anesthetizing effect. We aimed to evaluate if this effect will last till extubation, if given before pin removal. A total of 114 patients undergoing elective craniotomy were divided into three groups and were given 1 mg/kg of intravenous (IV), 2% lignocaine (Group 1), placebo (Group 2) and 1 mg/kg of 2% lignocaine sprayed down the endotracheal tube (Group 3) before skull pin removal. The effectiveness of each to blunt extubation response was compared. Plasma levels of lignocaine were measured 10 min after administration of the study drug and at extubation. Sedation scores were noted, immediately after extubation and 10 min later. Two percent of lignocaine instilled through endotracheal route was not superior to the IV route or placebo in attenuating cough or hemodynamic response at extubation when given 20-30 min before extubation. The plasma levels of lignocaine (0.8 μg/ml) were not high enough even at the end of 10 min to have a suppressive effect on cough if given IV or intratracheally (IT). Lignocaine did not delay awakening in these groups. IT lignocaine in the dose of 1 mg/kg does not prevent cough at extubation if given 20-30 min before extubation. If the action is by a local mucosal anesthetizing effect, it does not last for 20-30 min to cover the period from pin removal to extubation.


Morphologic and molecular alteration during tibia fracture healing in rat.
To monitor morphological feature and related osteogenic and bone metabolic change during healing of tibia fracture in a rat model. Tibia density and trabecular thickness were evaluated. Histopathology was examined by HE staining. Serous inflammatory factors IL-4, IL-6, TNF-α and metabolic biomarkers ALP, β-CTX, P1NP, were determined by ELISA. The expression of RUNX2, TGF-β1, VEGF-α, BMP-2, BMP-4, and BMP-7 in callus tissue were qualified by RT-PCR. Bone density decreased until week 4 and then increased post-operation. Trabeculae in callus were thickened over time with active osteogenesis. ELISA indicated the most severe inflammation at week 2, with the highest level of TNF-α, IL-6, and the lowest level of IL-4. After 4 weeks, the inflammation was alleviated accompanying with the decline of TNF-α and IL-6, while there was the elevation of IL-4. Bone metabolism showed active osteogenesis and resorption at week 6 with high P1NP and β-CTX. The expression of RUNX2, TGF-β1, VEGF-α, BMP-2, BMP-4, and BMP-7 increased progressively from week 1 to 6. The major lesions at week 2 in sham were tissue necrosis, periosteal reactive hyperplasia, inflammatory cell infiltration, capillary hyperplasia and slight fibro-blast cytopoiesis. At week 4, proliferation was greatly activated, fibrous callus shaped and chondrogenesis and some osteogenesis occurred at week 8. In rat model, bone density started to increase at week 6 after fracture, accompanied with trabeculae thickening, serous inflammatory factors decline, and peaked bone morphogenetic protein/growth factors, which indicated active osteogenesis was conforming to the classical phase of secondary fracture healing.


Morphological Effect on Wall Shear Stress in Intracranial Aneurysms.
Both high and low wall shear stress (WSS) play important roles in the development and rupture of intracranial aneurysms (IAs). This study aimed to determine the morphological factors that affect WSS in the IA and the parent artery. We studied a total of 66 IAs with three-dimensional imaging. Computational fluid dynamics (CFD) models were constructed and used to characterize the hemodynamics quantitatively. Aneurysms were grouped according to the mean neck width. The associations among hemodynamics and morphology were analyzed. Aspect ratio was correlated to lowest WSS (r = - 0.576), aneurysm-to-parent vessel (A-P) WSS ratio (r = - 0.500), and lowest-parent vessel (L-P) WSS ratio (r = - 0.575). Height-to-width ratio and height were correlated to WSS. Mean aneurysm WSS (p = 0.023), lowest WSS (p < 0.0001), highest-to-lowest WSS ratio (p = 0.004), L-P WSS ratio (p < 0.0001), highest-parent vessel (H-P) WSS ratio (p = 0.008), A-P WSS ratio (p < 0.001), and height (p < 0.001) were different between the two groups of aneurysms that were divided by the relationship between the diameters of the aneurysms and the necks. Multivariable analysis showed that the lowest WSS (p = 0.028) and A-P WSS ratio (p = 0.001) were independently associated with neck width. Morphological characteristics are associated with IA and parent vessel WSS. Aneurysms with different neck widths have different hemodynamics. These results could help in understanding the progression of IA and in building predictive models for IA rupture.


Performance Characteristics of Kidney Injury Molecule-1 In Relation to Creatinine, Urea, and Microalbuminuria in the Diagnosis of Kidney Disease.
The diagnosis and evaluation of impaired renal function remains a challenge owing to lack of reliable biomarker for assessment of kidney function. The existing panel of biomarkers currently displays several limitations, and recently kidney injury molecule-1 (KIM-1) has been suggested as a sensitive biomarker of renal function and proposed to enter clinical practice. This study was conducted to determine the diagnostic value of serum creatinine, urea, and microalbuminuria (MAU) in relation to the novel biomarker, KIM-1. Serum creatinine, urea, MAU, and KIM-1 were measured in forty individuals with and forty without kidney disease. Data were analyzed using multivariate methods of assessing diagnostic efficiency, test agreement, condition effects, and variability. The area under the receiver-operator characteristic curve revealed a diagnostic advantage of creatinine (0.924 ± 0.0066) and urea (0.925 ± 0.0068) over MAU (0.880 ± 0.078) and KIM-1 (0.35 ± 0.124). Overall diagnostic efficiency was higher for creatinine and urea (89.5% and 90.9%, respectively), followed by MAU (85.7%) and then KIM-1 (56.3%). Logistic regression analysis showed that creatinine and urea (R2 = 0.75 and R2 = 0.72, respectively, P < 0.001 for both) were better predictors of kidney disease than MAU (R2 = 0.64, P < 0.001) and KIM-1 (R2 = 0.046, P = 0.116). Further analysis of agreement showed that urea had an excellent agreement with creatinine (kappa r = 0.835, P < 0.001), with KIM-1 (kappa r = -0.198, P = 0.087) showing a poor agreement with creatinine. Our results indicate that elevated serum creatinine and urea above specific cutoff points reliably identifies patients with acute kidney injury or chronic kidney disease. However, more researches are warranted to further validate the diagnostic efficiency and application of MAU and for KIM-1 before its implementation in clinical practice.


Radiation from a D-dimensional collision of shock waves: a remarkably simple fit formula.
Recently we estimated the energy radiated in the head-on collision of two equal D-dimensional Aichelburg-Sexl shock waves, for even D, by solving perturbatively, to first order, the Einstein equations in the future of the collision. Here, we report on the solution for the odd D case. After finding the wave forms, we extract the estimated radiated energy for D=5, 7, 9, and 11 and unveil a remarkably simple pattern, given the complexity of the framework: (for all D) the estimated fraction of radiated energy matches the analytic expression 1/2-1/D, within the numerical error (less than 0.1%). Both this fit and the apparent horizon bound converge to 1/2 as D→∞.


Experience with misoprostol in the management of missed abortion in the second trimester.
The aim of this study was to determine the effectiveness and safety of misoprostol (cytotec, Searle) used during labour in women with missed abortion in the second trimester of pregnancy. Labour was induced in 42 women with missed abortion at the Women's Health and Action Research Centre, Benin City, Nigeria with intermittent vaginal administration of 100 microg tablets of misoprostol every 6 h. All women achieved successful vaginal delivery with five women requiring post-delivery uterine evacuation. The gestational ages of the women at the time of induction ranged between 13-24 weeks with a median of 17 weeks. The median dose of misoprostol resulting in successful delivery was 1,100 microgand ranged between 300 microg to 3,100 microg. Side-effects were minimal with five patients experiencing shivering, two women experiencing fever, while three vomited during the period of the induction. These results confirm the efficacy and safety of misoprostol for induction of labour in second trimester missed abortion in Nigerian women. We conclude that misoprostol is effective in the management of missed abortion in the second trimester in Nigeria.


Prophylactic Laparoscopic Total Gastrectomy with Jejunal Pouch Reconstruction in Patients Carrying a CDH1 Germline Mutation.
For patients with an identified germline E-cadherin-1 (CDH1) mutation, prophylactic gastrectomy is the treatment of choice to eliminate the high risk of developing diffuse gastric cancer. Laparoscopic total gastrectomy with jejunal pouch reconstruction is a novel approach that may be especially suitable in these patients. Patients with a germline CDH1 mutation who underwent prophylactic laparoscopic total gastrectomy with jejunal pouch were included in our prospective database. A total of 11 patients with a median age of 40 (22-61) years were included. The average operative time was 4:26 ± 0:49 h and the average blood loss was 219 ± 155 ml. Median length of hospital stay was 10 (7-27) days. In two patients, an esophagojejunal anastomotic leakage occurred (grade 4). The leakages were seen in patient numbers 2 and 3, which may be a result of a learning curve. The latter eight patients did not develop anastomotic leakage. Pulmonary complications occurred in one patient with atelectasis and in one patient with pneumonia (grade 2). The 60-day mortality rate was 0 %. Multiple foci of intramucosal diffuse gastric signet ring cell carcinoma were found in the resection specimen of 9/11 (82 %) patients. All 11/11 (100 %) resections were microscopically radical. Prophylactic laparoscopic total gastrectomy with jejunal pouch reconstruction in patients with a CDH1 germline mutation is feasible and safe. In 82 % of patients, foci of intramucosal diffuse gastric signet ring cell carcinoma in the resection specimen were found.


Spontaneous supersymmetry breaking in the 2D N=1 Wess-Zumino model.
We study the phase diagram of the two-dimensional N=1 Wess-Zumino model on the lattice using Wilson fermions and the fermion loop formulation. We give a complete nonperturbative determination of the ground state structure in the continuum and infinite volume limit. We also present a determination of the particle spectrum in the supersymmetric phase, in the supersymmetry broken phase and across the supersymmetry breaking phase transition. In the supersymmetry broken phase, we observe the emergence of the Goldstino particle.


[Relationship between risk factors of liver cancer and onset age in Ningxia Hui Autonomous Region].
Objective: To investigate the clinical data of patients with hepatocellular carcinoma in Ningxia Hui Autonomous Region through questionnaire survey, explore the association between the risk factors of liver cancer and the onset age of disease in this area and provide evidence for prevention and treatment of liver diseases. Methods: A retrospectively analysis was conducted in 250 patients with primary hepatocellular carcinoma by using their clinical data collected through questionnaire survey to understand the relationship between gender, smoking, alcohol use, hypertension, diabetes mellitus, hyperlipidemia, family history of liver cancer, liver cirrhosis, HBV infection, eating fish history and other factors and the incidence of hepatocellular carcinoma by univariate and logistic multivariate regression models. Results: Univariate regression analysis showed that hypertension, diabetes mellitus, hyperlipidemia and family history of liver cancer, HBV infection, cirrhosis, smoking, eating fish history were risk factors for the early onset of liver cancer, t=4.150, P<0.05; t=3.752, P<0.05; t=5.676, P<0.05; t=9.731, P<0.05; t=15.824, P<0.001; t=5.724, P<0.05; t=11.662, P<0.01; t=4.472, P<0.05, respectively, but logistic multivariate regression model analysis indicated that smoking, HBV infection were independent risk factors, OR=3.211(95%CI:1.134-4.642), OR=7.31(95%CI: 4.312-21.072). Conclusions: The risk factors affecting the age of liver cancer onset vary with area diet pattern alcohol use did not influenced the age of liver cancer onset, but smoking and HBV infection were the independent risk factors for early onset of liver cancer. It is necessary to strengthen the HBV infection prevention and control and advise people to quit smoking.


Prognostic value of multimarker analysis in stage III colorectal cancer: one step forward towards an individualized therapy decision.
Recently, we have analyzed new prognostic markers in colorectal cancer including neuroendocrine differentiation, overexpression of the sialyl-Lex antigen, overexpression of the peripheral benzodiazepine receptor (PBR), BAX protein expression and p53 mutational status. The predictive power of all markers in combination has not yet been evaluated. Between 1989 and 1991, 48 consecutive patients underwent surgery for stage III colorectal cancer at our hospital. All patients received a complete 5-year follow-up. Paraffin-embedded tumor samples were analyzed for all 5 markers. Multivariate discriminant analysis was performed to determine the prognostic value of all markers in combination. Based on these prognostic markers a mathematical discriminant function was obtained. This function allowed to correctly predict the further course of disease in 77% of the patients (specificity: 83.3%, sensitivity: 70.8%). The discriminant function was confirmed in another group of 19 patients. Single marker analysis allowed the prediction of the further course of disease only in 58-70%. Our study shows that in colorectal cancer, multimarker analysis is superior to unimarker analysis in predicting prognosis. The derived discriminant function allows patient stratification according to risk. Therefore, a multimarker analysis provides a rationale for future individualized risk-adapted therapies in stage III colorectal cancer.


Tissue and glomerular deposition of globulin aggregates.
We studied the behavior of AgGG, a model of iCs, in the rat. The clearance of radiolabeled AgGG from the circulation was found to follow first-order kinetics. The t1/2 of the AgGG increased markedly with increases in dose administered, whereas the absolute rate of removal appeared to approach a maximum. The bulk of the AgGG cleared was found in the liver, and less than 1% was found in spleen, lung, or kidney. All these features are typical of the behavior of macromolecules removed from the circulation by the RES. Specific glomerular deposition was studied at various dosages by isolating glomeruli and measuring the fraction of injected aggregate that was trapped. This fraction represented less than 10% of total renal deposits. Moreover, when animals were sacrificed at an interval of 1 t1/2 after the injection of the corresponding dose, the fraction deposited in glomeruli remained constant. The significance of this finding is discussed in relation to the pathogenesis of glomerulonephritis.


Urinary transforming growth factor-beta (TGF-beta) excretion and renal production of TGF-beta in rats with subtotal renal ablation: effect of enalapril and nifedipine.
The aim of the present study was to investigate the effect of enalapril and nifedipine on renal transforming growth factor-beta (TGF-beta) production and on the rate of urinary TGF-beta excretion in rats with subtotal renal ablation. After subtotal nephrectomy some animals were treated with enalapril or nifedipine. Renal cortical TGF-beta mRNA levels were 68% higher in untreated nephrectomized rats (p < 0.05) and 39% higher in rats treated with nifedipine (p < 0.05) compared with controls. There was no difference in renal cortical TGF-beta mRNA content between the nephrectomized rats treated with enalapril and sham animals, showing that enalapril treatment prevented the increase of TGF-beta mRNA in nephrectomized rats. The rate of urinary TGF-beta excretion was 2.2 +/- 0.8 pg/min in sham animals, 61.5 +/- 40.1 pg/min in untreated nephrectomized rats, 9.6 +/- 4.2 pg/min in nephrectomized rats treated with enalapril, and 55.2 +/- 24.46 pg/min in rats treated with nifedipine. The immunohistochemical reaction for TGF-beta in the renal cortex was less intense in the nephrectomized rats treated with enalapril than in the other groups of rats with subtotal renal ablation. These data show that enalapril induces a decrease in renal TGF-beta production and in urinary TGF-beta excretion in rats with subtotal renal ablation, an effect associated with the protective action of this treatment on renal structure and function and suggest that the determination of the rate of urinary TGF-beta could be a useful procedure for the evaluation of disease progression and therapeutic efficacy in the remnant kidney model.


Human cell-mediated rejection of porcine xenografts in an immunodeficient mouse model.
In this study, we describe the development of a novel experimental system in which rejection of porcine skin grafts by human peripheral blood cells can be studied directly in vivo in immunodeficient mice. To construct a small animal model of discordant xenograft rejection, recombinase-activating gene-deficient mice (R-) lacking both mature B and T cells were grafted with porcine skin grafts and administered, by adoptive cell transfer, human cells stimulated in vitro with irradiated porcine peripheral blood cells to create Hu-R- mice. R- mice accepted porcine skin grafts indefinitely without the need for immunosuppression. In contrast, Hu-R- mice were able to reject porcine skin grafts. Immunohistochemical analysis of rejecting skin grafts revealed the accumulation of human T cells around dermal porcine vessels and focally in the epidermis. Graft rejection was manifested by vascular endothelial cell proliferation, edema at the dermal-epidermal border, and perivascular hemorrhage. The tissue damage observed in the rejecting grafts was similar to that observed in delayed primate anti-porcine cell-mediated rejection of vascularized organ xenografts. The development and characterization of a small animal model, to study cellular immune responses of human cells to discordant xenografts in vivo, should provide a convenient means for asking mechanistic questions related to discordant xenotransplantation, and may also provide a practical system for testing new approaches designed to prevent xenograft rejection.


The neuropsychological rehabilitation of visual agnosia and Balint's syndrome.
Visual agnosia and Balint's syndrome are complex neurological disorders of the higher visual system that can have a remarkable impact on individuals' lives. Rehabilitation of these individuals is important to enable participation in everyday activities despite the impairment. However, the literature about the rehabilitation of these disorders is virtually silent. Therefore, the aim of this systematic review is to give an overview of available literature describing treatment approaches and their effectiveness with regard to these disorders. The search engines Psychinfo, Amed, and Medline were used, resulting in 22 articles meeting the criteria for inclusion. Only articles describing acquired disorders were considered. These articles revealed that there is some information available on the major subtypes of visual agnosia as well as on Balint's syndrome which practising clinicians can consult for guidance. With regard to the type of rehabilitation, compensatory strategies have proven to be beneficial in most of the cases. Restorative training on the other hand has produced mixed results. Concluding, although still scarce, a scientific foundation about the rehabilitation of visual agnosia and Balint's syndrome is evolving. The available approaches give valuable information that can be built upon in the future.


Bacterial chemotaxis and entropy production.
Entropy production is calculated for bacterial chemotaxis in the case of a migrating band of bacteria in a capillary tube. It is found that the speed of the migrating band is a decreasing function of the starting concentration of the metabolizable attractant. The experimentally found dependence of speed on the starting concentration of galactose, glucose and oxygen is fitted with power-law functions. It is found that the corresponding exponents lie within the theoretically predicted interval. The effect of the reproduction of bacteria on band speed is considered, too. The acceleration of the band is predicted due to the reproduction rate of bacteria. The relationship between chemotaxis, the maximum entropy production principle and the formation of self-organizing structure is discussed.


Obesity has an interactive effect with genetic variation in the activating transcription factor 6 gene on the risk of pre-diabetes in individuals of Chinese Han descent.
Endoplasmic reticulum (ER) stress is one of the contributing factors to the development of β-cell failure in type 2 diabetes. ER stress response through ATF6 has been shown to play an important role in insulin resistance and pancreatic β-cell function. We investigated whether genetic polymorphisms in ATF6 were associated with the risk of pre-diabetes in a Chinese Han population, and whether they had a synergistic effect with obesity. Our samples included 828 individuals who were diagnosed as pre-diabetic, and 620 controls. The minor allele A at rs2340721 was associated with increased risk for pre-diabetes(p = 0.013), and this association was still significant after adjusting for gender, age, body mass index (BMI), and waist-hip ratio(p' = 0.011). BMI, treated as a continuous variable, and rs2340721 had an interactive effect on pre-diabetic risk(p for interaction = 0.003, β = 0.106). Carriers of GG at rs7522210 were also at a higher risk compared to non-carriers (OR = 1.390, 95%CI:1.206-1.818, p = 0.013, adjusted OR' = 1.516, 95%CI:1.101-2.006, p' = 0.006). GG homozygotes had increased fasting blood glucose (FBG) levels(GG vs CX: 5.6 ± 0.52 vs 5.5 ± 0.57 mmol/L, p = 0.016), lower insulin levels (0,30,120 minutes after glucose load) (p < 0.05), and reduced areas under the insulin curve than non-carriers(GG vs CX:67.3(44.2-102.3) vs 73.1(49.4-111.4), p = 0.014). rs10918270 was associated with FBG, and rs4657103 with 2 hour glucose levels after a 75 g glucose load. We also identified a haplotype of TTAG composed of rs4657103, rs2134697, rs2340721, and rs12079579, which was associated with pre-diabetes. The genetic variation in ATF6 is associated with pre-diabetes and has interactive effects with BMI on pre-diabetes in the Chinese Han population.


Sequential imaging of an impacted mandibular second premolar migrated from angle to condyle.
Extreme distal migration of impacted teeth to the subcondylar area and condyle is very rare. Using an interesting sequence of radiographs showing the path of the tooth in the mandible, we describe the intrabony migration of a mandibular second premolar from angle to condyle in a young woman. Cone-beam computed tomography was used to establish the precise location of the tooth.


Metabolic control analysis for large changes: extension to variable elasticity coefficients.
Modular approaches are powerful systems biology strategies to deal with complexity. They consist in lumping conceptually all that is irrelevant to the problem under study, leaving explicit the portions of interest. Modular (or top-down) metabolic control analysis is a theoretical and experimental approach to study the sensitivity properties of complex metabolic systems. Initially, it was conceived for infinitesimal changes but, recently, it started to be developed for large metabolic changes. A central result of this approach is that the systemic properties, represented by control coefficients, can be expressed as a function of the properties of isolated modules, the elasticity coefficients. Here we extend the theory for large changes to the case that the elasticity coefficients depend on the extent of the change. The novel theory is used to analyse experimental data related to the control of glycolytic flux in Escherichia coli. Our analysis shows that the pattern of control for large changes is quantitatively and qualitatively different from the one obtained applying the infinitesimal treatment.


Inhibition of casein kinase 2 blocks G2/M transition in early embryo mitosis but not in oocyte meiosis in mouse.
Casein kinase 2 (CK2) is a highly conserved, ubiquitously expressed serine/threonine protein kinase with hundreds of substrates. The role of CK2 in the G2/M transition of oocytes, zygotes, and 2-cell embryos was studied in mouse by enzyme activity inhibition using the specific inhibitor 4, 5, 6, 7-tetrabromobenzotriazole (TBB). Zygotes and 2-cell embryos were arrested at G2 phase by TBB treatment, and DNA damage was increased in the female pronucleus of arrested zygotes. Further developmental ability of arrested zygotes was reduced, but that of arrested 2-cell embryos was not affected after releasing from inhibition. By contrast, the G2/M transition in oocytes was not affected by TBB. These results indicate that CK2 activity is essential for mitotic G2/M transition in early embryos but not for meiotic G2/M transition in oocytes.


Alignment in local approaches to alcohol and cannabis control policy: A case study of California cities and counties.
Public health experts have urged governments around the world to regulate newly legalized cannabis as they do alcohol to effectively and efficiently protect health. However, research evaluating the alignment of alcohol and cannabis policies is sparse. We assessed similarities and differences in local alcohol and cannabis control policies across California, and characterized localities adopting distinct policy approaches. Using standard legal epidemiologic techniques, we collected and coded local alcohol and cannabis control policies relevant to public health for 12 California counties and all incorporated cities within them (N=241). We assessed whether localities were equally stringent on alcohol and cannabis policies by comparing overall restrictiveness (summed policy scores) and 9 specific provisions that applied to both substances. We captured distinct local alcohol-cannabis policy approaches using latent class analysis, and examined this classification in relation to local demographic, socioeconomic, political, and retail market characteristics. All 241 localities permitted alcohol sales, while 71% banned cannabis sales. Among those that did not ban cannabis sales, more stringent alcohol policy scores were associated with more stringent cannabis policy scores (linear regression coefficient: 0.16 [95% CI: 0.07, 0.25]). Local governments rarely adopted the same provisions for alcohol and cannabis (e.g., limits on hours of sale, advertising restrictions), and only two regulated the co-location of cannabis and alcohol outlets. Localities that were restrictive on alcohol yet permissive on cannabis (12%) were more urban, politically progressive, and had more low-income and racial/ethnic minority residents. Localities that were more permissive on alcohol and restrictive on cannabis (51%) were more socioeconomically advantaged. We found few similarities between local alcohol and cannabis control policies. California's experience suggests that, as governments around the world legalize cannabis, lessons learned from regulating alcohol are not routinely applied to cannabis, particularly in communities distinguished by high social and economic advantages.


Pilot Phase II study of mazindol in children with attention deficit/hyperactivity disorder.
Mazindol has been proposed as a potential treatment of children with attention deficit/hyperactivity disorder (ADHD). The purpose of this pilot study was to assess its pharmacokinetics, short-term efficacy, and safety. A total of 24 children (aged 9-12 years) with ADHD (according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, text-revision criteria) received a daily dose of 1 mg for 7 days and were followed for 3 additional weeks. Pharmacokinetic samples were collected after the first administration. ADHD symptoms were assessed using the ADHD Rating Scale (RS)-IV, Conners' Parent Rating Scale - Revised: Long (CPRS-R:L) at screening, baseline, and the end of the study. The Clinical Global Impression - Severity (CGI-S) scale was assessed at baseline, and the CGI - Improvement (CGI-I) scale was assessed at subsequent visits. Twenty-one subjects (aged 10±1 years) were analyzed. Pharmacokinetic data were described by a one-compartment model with first-order absorption, elimination, and lag time. The typical apparent clearance and apparent volume of distribution were 27.9 L/h and 234 L, and increased with fat-free mass and age, respectively. The mean change in score in ADHD RS-IV after 1 week of mazindol was -24.1 (P<0.0001), greater than a 90% improvement from baseline. Reduction of CPRS-R:L and CGI-S scores were -52.1 (P<0.0001) and -2.5 (P<0.01), respectively. Adverse events were mild to moderate, decreased appetite and upper abdominal pain being the most common. This preliminary study shows that mazindol might be an effective, well-tolerated, and long-acting (more than 8 hours) agent for the treatment of ADHD in children.


[Evaluation of influence of selenium, copper, zinc and iron concentrations on thyroid gland size in school children with normal ioduria].
Proper diet with regard to quantity and quality of meals is of vital importance for normal development and functioning of the organism. There are many proofs that environmental factors play an important role in the pathogenesis of goiter. Iodine deficit in diet is best known of all factors contributing to goiter. Deficit of other elements like, iron, selenium, copper and zinc is also essential. The purpose of this study was to evaluate the influence of chosen environmental factors, i.e., iron and trace elements of selenium, zinc and copper--essential for the thyroid functioning on the development of goiter in school children aged 6-13 years with normal ioduria in the Polish population. In 2002, the study was performed in 4 elementary schools chosen randomly in Białystok and in the Children's Outpatient Clinic of Endocrinology of the Specialist Regional Hospital. The study included 400 children aged 7-13 years from schools and 120 patients at the same age treated with KJ and/or tyroxine for minimum 12 months due to goiter in the Out-patient Clinic of Endocrinology. Basing on the assessment of the thyroid size as well as the criteria of WHO from 1997 year for body surface and sex, children were divided into 2 subgroups: with goiter and the thyroid gland within the norm. Children aged 9-11 years were qualified and chosen from subgroups to further examinations. In both subgroups, blood samples were taken to determine concentrations of iron, selenium, copper and zinc. The mean concentration of selenium in the blood was statistically significantly lower in children with goiter in comparison with children with the thyroid gland within the norm (44.4 +/- 7.8 microg/L vs. 49.2 +/- 9.1 microg/L, p = 0.044) in the study population of school children and the Outpatient Clinic of Endocrinology. No differences of serum iron concentrations were observed in children with goiter and with the thyroid gland within the norm. However, nearly the half (45.5%) of patients with the lower serum concentration of iron (< 60 microg/dL) had goiter despite average 22-month therapy with KJ and/or tyroxine. Observed, in spite of proper iodine prophylaxis, 7% rate of goiter occurring in school children suggests other than iodine deficiency factors that influence goiter development. The study proved that the low concentration of iron and/or selenium deficit found in the serum of children with goiter in spite of their treatment with KJ and/or tyroxine may be additional factors influencing the effectiveness of this treatment.


Processing efficiency of divided spatial attention mechanisms in human visual cortex.
Many visual tasks require deployment of attention to multiple objects or locations. We used functional magnetic resonance imaging and behavioral experiments to investigate the relative processing efficiency of two putative attentional mechanisms for performing such tasks: the "zoom lens" and "multiple spotlights." Two key questions were investigated: (1) does splitting the spotlight into multiple foci incur an overhead cost that diminishes the efficacy of attention compared with the zoom lens, and (2) does splitting the spotlight provide a benefit relative to the zoom lens by conserving attention resources that otherwise would be directed to task irrelevant stimuli? For both mechanisms, attending to multiple object locations decreased processing efficiency at a single location, resulting in both decreased behavioral performance and decreased blood oxygenation level-dependent (BOLD) signal attentional modulation. When the two mechanisms attended to multiple objects across the same spatial extent, the multiple spotlight mechanism, which ignores intervening stimuli, yielded better performance and higher BOLD signal. When the two mechanisms processed the same number of stimuli, splitting the spotlight neither impaired performance nor diminished BOLD signal in occipital cortex. The surprising efficiency of the multiple spotlight mechanism supports the emerging view that spatial attention is easily deployed in a diverse range of spatial configurations.


Facile Synthesis of Ultrastable Porous Aromatic Frameworks by Suzuki-Miyaura Coupling Reaction for Adsorption Removal of Organic Dyes.
Porous aromatic frameworks (PAFs) with robust structure, high stability, and high surface area have attracted intense interest from scientists in diverse fields. However, there are still very few reports on the adsorption of organic dyes by PAFs. In this work, four new PAFs have been facilely synthesized by the polymerization of a tetrahedral-shaped (four-node) monomer with a series of three-node monomers through Suzuki-Miyaura coupling reactions. All the obtained materials possess hierarchical porous structures and show high thermal and chemical stability. The Brunauer-Emmett-Teller (BET) surface areas of these PAFs were determined to be 857 m2 g-1 for PAF-111, 526 m2 g-1 for PAF-112A, 725 m2 g-1 for PAF-112B, and 598 m2 g-1 for PAF-113. Rhodamine B was selected as a model organic dye to test the adsorption capacities of the obtained PAF materials. PAF-111 showed a maximum adsorption capacity of 1666 mg g-1 (167 wt %) for Rhodamine B, which is among the highest values reported to date for porous organic materials. It is noteworthy that PAF-111 could be reused in at least ten cycles under the adsorption conditions without any loss of adsorption capacity. Our study has revealed the great potential and advantages of PAFs as ultrastable adsorption materials for the removal of organic dyes.


The Shock Pulse Index and Its Application in the Fault Diagnosis of Rolling Element Bearings.
The properties of the time domain parameters of vibration signals have been extensively studied for the fault diagnosis of rolling element bearings (REBs). Parameters like kurtosis and Envelope Harmonic-to-Noise Ratio are the most widely applied in this field and some important progress has been made. However, since only one-sided information is contained in these parameters, problems still exist in practice when the signals collected are of complicated structure and/or contaminated by strong background noises. A new parameter, named Shock Pulse Index (SPI), is proposed in this paper. It integrates the mutual advantages of both the parameters mentioned above and can help effectively identify fault-related impulse components under conditions of interference of strong background noises, unrelated harmonic components and random impulses. The SPI optimizes the parameters of Maximum Correlated Kurtosis Deconvolution (MCKD), which is used to filter the signals under consideration. Finally, the transient information of interest contained in the filtered signal can be highlighted through demodulation with the Teager Energy Operator (TEO). Fault-related impulse components can therefore be extracted accurately. Simulations show the SPI can correctly indicate the fault impulses under the influence of strong background noises, other harmonic components and aperiodic impulse and experiment analyses verify the effectiveness and correctness of the proposed method.


Physiologically based pharmacokinetic modelling prediction of the effects of dose adjustment in drug-drug interactions between levonorgestrel contraceptive implants and efavirenz-based ART.
HIV-positive women receiving efavirenz-based ART and levonorgestrel contraceptive implants are at risk of low levonorgestrel exposure and unintended pregnancy. To investigate clinically applicable dose-adjustment strategies to overcome the known drug-drug interaction (DDI) between levonorgestrel and efavirenz, using a physiologically based pharmacokinetic (PBPK) modelling-based approach. A PBPK model was qualified against clinical data to predict levonorgestrel plasma concentrations when standard-dose (150 mg) levonorgestrel implants were administered alone (control group), as well as when standard-dose or increased-dose (300 mg) levonorgestrel implants were coadministered with either 600 or 400 mg of efavirenz. No difference was seen between in vivo clinical and PBPK-model-simulated levonorgestrel plasma concentrations (P > 0.05). Simulated levonorgestrel plasma concentrations were ∼50% lower at 48 weeks post-implant-placement in virtual individuals receiving standard-dose levonorgestrel with either 600 or 400 mg of efavirenz compared with the control group (efavirenz:control geometric mean ratio = 0.42 and 0.49, respectively). Conversely, increased-dose levonorgestrel in combination with either 600 or 400 mg of efavirenz was sufficient to restore levonorgestrel concentrations to levels similar to those observed in the 150 mg levonorgestrel control group 48 weeks post-implant-placement (efavirenz:control geometric mean ratio = 0.86 and 1.03, respectively). These results suggest that the clinically significant DDI between efavirenz and levonorgestrel is likely to persist despite efavirenz dose reduction, whereas dose escalation of implantable levonorgestrel may represent a successful clinical strategy to circumvent efavirenz-levonorgestrel DDIs and will be of use to inform clinical trial design to assess coadministration of efavirenz and levonorgestrel implants.


Codelivery of Que and BCL-2 siRNA with Lipid-Copolymer Hybrid Nanocomplexes for Efficient Tumor Regression.
The efficacy of chemotherapy is often reduced due to the chemotherapy resistance of tumor cells, which is usually caused by abnormal gene overexpression. Herein, multifunctional nanocomplexes (Que/siBCL2@BioMICs) were developed to deliver quercetin (Que) and BCL-2 siRNA (siBCL2) to synergistically inhibit tumor growth. The nanocomplexes were composed of an amphiphilic triblock copolymer of poly(ethylene glycol) methyl ether methacrylate-poly[2-(dimethylamino) ethyl acrylate]-polycaprolactone (PEGMA-PDMAEA-PCL) and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-poly(ethylene glycol)-biotin (DSPE-PEG-biotin). Que was encapsulated into the cores through hydrophobic interactions, while negatively charged siBCL2 was loaded through electrostatic interactions. The nanocomplexes could effectively facilitate cellular uptake via biotin-mediated active targeting and cytosolic release of cargos by the "proton sponge effect" of PDMAEA. Que/siBCL2@BioMICs achieved enhanced cytotoxicity and anti-metastasis activity due to a synergistic effect of Que and siBCL2 in vitro. More importantly, superior anti-tumor efficacy was observed in orthotopic 4T1 tumor-bearing mice with reduced primary tumor burden and lung metastatic nodules, while no obvious side effects to major organs were observed. In conclusion, the biotin-targeted nanocomplexes with chemotherapeutic and nucleotide agent entrapment provide a promising strategy for efficient triple-negative breast cancer (TNBC) therapy.


Socio-economic, dietary, activity, nutrition and body weight transitions in South Korea.
Socio-economic development influences many factors that affect health, especially diet and nutrition. This investigation proposes that a system of transitions occur as societies develop, with socio-economic, physical activity, dietary, nutrition and body weight transitions operating in relationship with each other. This model of transitions was examined empirically using South Korea as an example of a nation that has undergone considerable changes. Data were drawn from published government reports: the Korean National Nutrition Survey and annual reports at the national level for the years between 1969 and 1993. The socio-economic transition was assessed by gross national product. The physical activity transition was assessed using annual proportions of the population involved in primary, secondary and tertiary industries, as well as the number of cars and driver's licences. The dietary transition was measured by plant and animal food consumption. The nutrition transition was assessed by percentages of energy from carbohydrate, protein and fat. The body weight transition was measured by body mass index calculated from the average height and weight of adolescents. Results revealed that the transitions were highly correlated as expected, with the socio-economic transition exhibiting major changes. South Koreans tended to decrease their physical activity and plant food consumption, and to increase animal food consumption, percentage of energy from dietary fat and body weight, in relationship to the socio-economic transition. Examining a system of transitions on a national level in one country that has undergone rapid economic development may provide a strategy for examining how such transitions operate in other nations.


ABCB1 genetic variability and methadone dosage requirements in opioid-dependent individuals.
The most common treatment for opioid dependence is substitution therapy with another opioid such as methadone. The methadone dosage is individualized but highly variable, and program retention rates are low due in part to nonoptimal dosing resulting in withdrawal symptoms and further heroin craving and use. Methadone is a substrate for the P-glycoprotein transporter, encoded by the ABCB1 gene, which regulates central nervous system exposure. This retrospective study aimed to investigate the influence of ABCB1 genetic variability on methadone dose requirements. Genomic deoxyribonucleic acid was isolated from opioid-dependent subjects (n = 60) and non-opioid-dependent control subjects (n = 60), and polymerase chain reaction-restriction fragment length polymorphism and allele-specific polymerase chain reaction were used to determine the presence of single nucleotide polymorphisms at positions 61, 1199, 1236, 2677, and 3435. ABCB1 haplotypes were inferred with PHASE software (version 2.1). There were no significant differences in the allele or genotype frequencies of the individual single nucleotide polymorphisms or haplotypes between the 2 populations. ABCB1 genetic variability influenced daily methadone dose requirements, such that subjects carrying 2 copies of the wild-type haplotype required higher doses compared with those with 1 copy and those with no copies (98.3 +/- 10.4, 58.6 +/- 20.9, and 55.4 +/- 26.1 mg/d, respectively; P = .029). In addition, carriers of the AGCTT haplotype required significantly lower doses than noncarriers (38.0 +/- 16.8 and 61.3 +/- 24.6 mg/d, respectively; P = .04). Although ABCB1 genetic variability is not related to the development of opioid dependence, identification of variant haplotypes may, after larger prospective studies have been performed, provide clinicians with a tool for methadone dosage individualization.


Disturbed flow promotes deposition of leucocytes from flowing whole blood in a model of a damaged vessel wall.
Departure from simple laminar flow in arteries may promote the local attachment of leucocytes either to intact endothelium or platelet thrombi. We perfused blood through a chamber with a backward facing step, to observe whether adhesion from whole blood to P-selectin was indeed localized to a region of recirculating flow, and whether platelets binding to collagen in such a region could capture leucocytes. Blood flowing over the step established a stable vortex, a reattachment point where forward and backward flow separated, and a simple laminar flow with wall shear rate c. 400/s further downstream. Fluorescently labelled leucocytes were observed to attach to P-selectin immediately upstream or downstream of the reattachment point, and to roll back towards the step or away from it, respectively. There was negligible adhesion further downstream. When a P-selectin-Fc chimaera was used to coat the chamber, stable attachment occurred, again preferentially in the disturbed flow region. Numerous platelets adhered to a collagen coating throughout the chamber, although there were local maxima either side of the reattachment point. The adherent platelets captured flowing leucocytes in these regions alone. Leucocytes may adhere from flowing blood in vessels with high shear rate if the flow is disturbed. While platelets can adhere over a wider range of shear rates, their ability to capture leucocytes may be restricted to regions of disturbed flow.


Organizational learning during COVID-19: A qualitative study of nurses' experiences.
The aim of this study is to test the validity of the Organizational Learning in Hospitals model in the context of the COVID-19 pandemic. Organizational learning is especially crucial in circumstances of intense, complex, enduring change, as with the COVID-19 pandemic. Nurse managers need additional guidance for fostering organizational learning under such circumstances. The Organizational Learning in Hospitals model may be a helpful resource but requires additional validation. Semi-structured interviews were conducted to gather 19 nurses' first-hand experiences of organizational learning during the COVID-19 pandemic. Data were analysed using deductive thematic analysis. Nurses' experiences of organizational learning generally aligned with the tenets of the model. Specifically, effective organizational learning occurred when the contextual factors and mechanisms portrayed in the model converged. Model and contrary cases illustrate this phenomenon. This study validates and adds context to the model. It offers practical examples of the contextual factors and mechanisms of organizational learning. Leaders can use the model to guide their efforts to foster organizational learning. This study reaffirms the importance of nurse leaders' central role in organizational learning. Nurse leaders can use the Organizational Learning in Hospitals model, and the practical examples provided, to foster organizational learning during challenging times.


Educational interventions for general practitioners to identify and manage depression as a suicide risk factor in young people: a systematic review and meta-analysis protocol.
Suicide is a major public health problem and globally is the second leading cause of death in young adults. Globally, there are 164,000 suicides per year in young people under 25 years. Depression is a strong risk factor for suicide. Evidence shows that 45% of those completing suicide, including young adults, contact their general practitioner rather than a mental health professional in the month before their death. Further evidence indicates that risk factors or early warning signs of suicide in young people go undetected and untreated by general practitioners. Healthcare-based suicide prevention interventions targeted at general practitioners are designed to increase identification of at-risk young people. The rationale of this type of intervention is that early identification and improved clinical management of at-risk individuals will reduce morbidity and mortality. This systematic review will synthesise evidence on the effectiveness of education interventions for general practitioners in identifying and managing depression as a suicide risk factor in young people. We shall conduct a systematic review and meta-analysis following the Cochrane Handbook for Systematic Reviews of Interventions guidelines and conform to the reporting guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement recommendations. Electronic databases will be systematically searched for randomised controlled trials and quasi-experimental studies investigating the effectiveness of interventions for general practitioners in identifying and managing depression as a suicide risk factor in young people in comparison to any other intervention, no intervention, usual care or waiting list. Grey literature will be searched by screening trial registers. Only studies published in English will be included. No date restrictions will be applied. Two authors will independently screen titles and abstracts of potential studies. The primary outcome is identification and management of depression. Secondary outcomes are suicidal ideation, suicide attempts, deliberate self-harm, knowledge of suicide risk factors and suicide-related behaviours, attitudes towards suicide risk and suicide-related behaviours, confidence in dealing with suicide risk factors and suicide-related behaviour. Our study will inform the development of future education interventions and provide feasibility and acceptability evidence, to help general practitioners identify and manage suicidal behaviour in young people. PROSPERO registration number: CRD42014009110.


Psychophysiological sexual arousal in women with a history of child sexual abuse.
On the basis of literature that suggests that child sexual abuse (CSA) survivors with post traumatic stress disorder (PTSD) have higher baseline sympathetic nervous system (SNS) activity than healthy controls and research that suggests that the SNS plays a critical role in female physiological sexual arousal, we examined the impact of SNS activation through intense exercise on sexual arousal in women with CSA and PTSD. We measured physiological and subjective sexual arousal in women with CSA (n = 8), women with CSA and PTSD (n = 10), and healthy controls (n = 10) during exposure to nonerotic and erotic videos. After exercise, women with CSA and women with CSA and PTSD showed no significant differences in the physiological sexual response compared with no exercise, which was different from the increased physiological sexual response after exercise observed in control women.


Integrating habits and practices data for soaps, cosmetics and air care products into an existing aggregate exposure model.
In order to accurately assess aggregate exposure to a fragrance material in consumers, data are needed on consumer habits and practices, as well as the concentration of the fragrance material in those products. The present study describes the development of Phase 2 Creme RIFM model by expanding the previously developed Phase 1 model to include an additional six product types. Using subject-matching algorithms, the subjects in the Phase 1 Creme RIFM database were paired with subjects in the SUPERB and BodyCare surveys based on age and gender. Consumption of the additional products was simulated to create a seven day diary allowing full data integration in a consistent format. The inhalation route was also included for air care and other products where a fraction of product used is inhaled, derived from the RIFM 2-box model. The expansion of the Phase 1 Creme RIFM model has resulted in a more extensive and refined model, which covers a broader range of product categories and now, includes all relevant routes of exposure. An evaluation of the performance of the model has been carried out in an accompanying publication to this one.