Tensile and Viscoelastic Behavior in Nacre-Inspired Nanocomposites: A Coarse-Grained Molecular Dynamics Study.
Organisms hold an extraordinarily evolutionary advantage in forming complex, hierarchical structures across different length scales that exhibit superior mechanical properties. Mimicking these structures for synthesizing high-performance materials has long held a fascination and has seen rapid growth in the recent past thanks to high-resolution microscopy, design, synthesis, and testing methodologies. Among the class of natural materials, nacre, found in mollusk shells, exhibits remarkably high mechanical strength and toughness. The highly organized "brick and mortar" structure at different length scales is a basis for excellent mechanical properties and the capability to dissipate energy and propagation in nacre. Here, we employ large-scale atomistic coarse-grained molecular dynamics simulations to study the mechanical and viscoelastic behavior of nacre-like microstructures. Uniaxial tension and oscillatory shear simulations were performed to gain insight into the role of complex structure-property relationships. Specifically, the role played by the effect of microstructure (arrangement of the crystalline domain) and polymer-crystal interactions on the mechanical and viscoelastic behavior is elucidated. The tensile property of the nanocomposite was seen to be sensitive to the microstructure, with a staggered arrangement of the crystalline tablets giving rise to a 20-30% higher modulus and lower tensile strength compared to a columnar arrangement. Importantly, the staggered microstructure is shown to have a highly tunable mechanical behavior with respect to the polymer-crystal interactions. The underlying reasons for the mechanical behavior are explained by showing the effect of polymer chain mobility and orientation and the load-carrying capacity for the constituents. Viscoelastic responses in terms of the storage and loss moduli and loss tangent are studied over three decades in frequency and again highlight the differences brought about by the microstructure. We show that our coarse-grained models offer promising insights into the design of novel biomimetic structures for structural applications.


The benefits of interprofessional education 10 years on.
Interprofessional education (IPE) was first conceived in 1973 by a World Health Organization (WHO) expert group in Geneva. WHO member states were then charged with implementing medical education IPE pilot projects and from then to today there has a been a rapid proliferation in the number of publications on the subject. IPE has generated research into its use, conferences specific to IPE, organisations dedicated to it and policy championing it. The authors question whether there has been any major shift in the silos in which different professions might be working. The authors published an article on the benefits of IPE ( Illingworth and Chelvanayagam, 2007 ). Ten years have now passed and many changes have been implemented and experienced in health and social care and therefore a review of the literature is required. Also, it is 7 years since the publication of WHO's report outlining the role of IPE in the preparation of health professionals ( WHO, 2010 ) and, increasingly, UK Government policy champions collaborative and integrated working. The conclusions from the 2007 article acknowledged the development of IPE; however, it highlighted the need for empirical evidence to demonstrate the effectiveness of IPE in service user and carer outcomes. This article will explore whether IPE has achieved the benefits discussed in the previous article and what developments have occurred since it was published.


Superoxide dismutase mimetic drug tempol aggravates anti-GBM antibody-induced glomerulonephritis in mice.
Oxidative stress plays an important role in the pathogenesis of anti-glomerular basement membrane antibody-induced glomerulonephritis (anti-GBM-GN). Superoxide dismutase (SOD) is the first line of defense against oxidative stress by converting superoxide to hydrogen peroxide (H(2)O(2)). We investigated the effect of the SOD mimetic drug tempol on anti-GBM-GN in mice. 129/svJ mice were challenged with rabbit anti-mouse-GBM sera to induce GN and subsequently divided into tempol (200 mg.kg(-1).day(-1), orally) and vehicle-treated groups. Routine histology, SOD and catalase activities, malondialdehyde (MDA), H(2)O(2), and immunohistochemical staining for neutrophils, lymphocytes, macrophages, p65-NF-kappaB, and osteopontin were performed. Mice with anti-GBM-GN had significantly reduced renal SOD and catalase activities and increased H(2)O(2) and MDA levels. Unexpectedly, tempol administration exacerbated anti-GBM-GN as evidenced by intensification of proteinuria, the presence of severe crescentic GN with leukocyte influx, and accelerated mortality in the treated group. Tempol treatment raised SOD activity and H(2)O(2) level in urine, upregulated p65-NF-kappaB and osteopontin in the kidney, but had no effect on renal catalase activity. Thus tempol aggravates anti-GBM-GN by increasing production of H(2)O(2) which is a potent NF-kappaB activator and as such can intensify inflammation and renal injury. This supposition is supported by increases seen in p65-NF-kappaB, osteopontin, and leukocyte influx in the kidneys of the tempol-treated group.


Rapid lipid enrichment in omega3 fatty acids: plasma data.
The bolus intravenous injection of a novel medium-chain triglyceride:fish oil emulsion to normal subjects was recently reported to enrich within 60 min the phospholipid content of leucocytes and platelets in long-chain polyunsaturated omega3 fatty acids. The present study, conducted in second generation omega3-depleted rats, aimed at investigating whether such a procedure may also increase within 60 min the phospholipid content of omega3 fatty acids in cells located outwards the bloodstream, in this case liver cells, and whether this coincides with correction of the perturbation in the liver triglyceride fatty acid content and profile otherwise prevailing in these rats. This first report deals mainly with the fatty acid pattern of plasma lipids in male omega3-depleted rats that were non-injected or injected with either the omega3-rich emulsion or a control medium-chain triglyceride:olive oil emulsion. The results provide information on the fate of the exogenous lipids present in the lipid emulsions and injected intravenously 60 min before sacrifice. Moreover, in the uninjected omega3-depleted rats the comparison between individual plasma and liver measurements indicated positive correlations in the fatty acid profile of phospholipids and triglycerides.


What is the most suitable grid for computer perimetry in glaucoma patients?
100 eyes with suspected or proven glaucoma were examined with the Humphrey Field Analyzer 620 with 30-1 and 30-2 threshold tests, complementary 6 degrees grids which combine to a 4.2 degrees grid. The two tests were compared with each other in the resulting 68 pathological fields. 29 of them showed obvious differences in detection of scotomas. In 11 fields, the differences were so great that isolated consideration would have led to an incorrect staging of the glaucoma. Therefore, at present both tests should be applied in glaucoma cases. The frequency of different scotoma detection per test location was more than 10 times higher in the center than in the periphery. It is suggested that a program is developed with a 3 degrees grid within 10 degrees eccentricity, a 4.2 degrees grid between 10 degrees and 20 degrees and a 6 degrees grid between 20 degrees and 30 degrees eccentricity.


Effect of elevated CO2 and high temperature on seed-set and grain quality of rice.
Hybrid vigour may help overcome the negative effects of climate change in rice. A popular rice hybrid (IR75217H), a heat-tolerant check (N22), and a mega-variety (IR64) were tested for tolerance of seed-set and grain quality to high-temperature stress at anthesis at ambient and elevated [CO(2)]. Under an ambient air temperature of 29 °C (tissue temperature 28.3 °C), elevated [CO(2)] increased vegetative and reproductive growth, including seed yield in all three genotypes. Seed-set was reduced by high temperature in all three genotypes, with the hybrid and IR64 equally affected and twice as sensitive as the tolerant cultivar N22. No interaction occurred between temperature and [CO(2)] for seed-set. The hybrid had significantly more anthesed spikelets at all temperatures than IR64 and at 29 °C this resulted in a large yield advantage. At 35 °C (tissue temperature 32.9 °C) the hybrid had a higher seed yield than IR64 due to the higher spikelet number, but at 38 °C (tissue temperature 34-35 °C) there was no yield advantage. Grain gel consistency in the hybrid and IR64 was reduced by high temperatures only at elevated [CO(2)], while the percentage of broken grains increased from 10% at 29 °C to 35% at 38 °C in the hybrid. It is concluded that seed-set of hybrids is susceptible to short episodes of high temperature during anthesis, but that at intermediate tissue temperatures of 32.9 °C higher spikelet number (yield potential) of the hybrid can compensate to some extent. If the heat tolerance from N22 or other tolerant donors could be transferred into hybrids, yield could be maintained under the higher temperatures predicted with climate change.


Electron transfer to nitrogenase. Characterization of flavodoxin from Azotobacter chroococcum and comparison of its redox potentials with those of flavodoxins from Azotobacter vinelandii and Klebsiella pneumoniae (nifF-gene product).
Flavodoxin in the hydroquinone state acts as an electron donor to nitrogenase in several nitrogen-fixing organisms. The mid-point potentials for the oxidized-semiquinone and semiquinone-hydroquinone couples of flavodoxins isolated from facultative anaerobe Klebsiella pneumoniae (nifF-gene product, KpFld) and the obligate aerobe Azotobacter chroococcum (AcFld) were determined as a function of pH. The mid-point potentials of the semiquinone-hydroquinone couples of KpFld and AcFld are essentially independent of pH over the range pH 7-9, being -422 mV and -522 mV (normal hydrogen electrode) at pH 7.5 respectively. The mid-point potentials of the quinone-semiquinone couples at pH 7.5 are -200 mV (KpFld) and -133 mV (AcFld) with delta Em/pH of -65 +/- 4 mV (KpFld) and -55 +/- 2 mV (AcFld) over the range pH 7.0-9.5. This indicates that reduction of the quinone is coupled to protonation to yield a neutral semiquinone. The significance of these values with respect to electron transport to nitrogenase is discussed. The amino acid compositions, the N- and C-terminal amino acid sequences and the u.v.-visible spectra of KpFld and AcFld were determined and are compared with published data for flavodoxins isolated from Azotobacter vinelandii.


Experimental modelling of single-particle dynamic processes in crystallization by controlled colloidal assembly.
In the last few decades, the controlled colloidal assembly was adopted as a new modelling technology for the study of the crystallization mechanism. In colloidal systems, the movement of particles is slow enough to follow and the particle dynamics can be monitored at the single-particle level using normal optical microscopes. So far, the studies of colloidal crystallization have produced a number of insights, which have significantly improved our understanding of crystallization. In this review, we summarize the recent advances in understanding the mechanism of crystallization, which were achieved using colloidal model systems, i.e., the kinetics of nucleation, growth and defect formation. Such model systems allow us to not only visualize some "atomic" details of nucleation and surface processes of crystallization, but also quantify previous models to such an extent that has never been achieved before by other approaches. In the case of nucleation, the quantitative observation of the kinetic process was made at the single-particle level; the results include the ideal case and the deviations from classical theories. The deviations include multi-step crystallization, supersaturation-driven structural mismatch nucleation, defect creation and migration kinetics, surface roughening, etc. It can be foreseen that this approach will become a powerful tool to study the fundamental process of crystallization and other phase transitions.


Online Public Attention Toward Premature Ejaculation in Mainland China: Infodemiology Study Using the Baidu Index.
Premature ejaculation (PE) is one of the most described psychosocial stress and sexual complaints worldwide. Previous investigations have focused predominantly on the prospective identification of cases that meet researchers' specific criteria. The genuine demand from patients with regard to information on PE and related issues may thus be neglected. This study aims to examine the online search trend and user demand related to PE on a national and regional scale using the dominant major search engine in mainland China. The Baidu Index was queried using the PE-related terms for the period of January 2011 to December 2020. The search volume for each term was recorded to analyze the search trend and demographic distributions. For user interest, the demand and trend data were collected and analyzed. Of the 36 available PE search keywords, 4 PE searching topics were identified. The Baidu Search Index for each PE topic varied from 46.30% (86,840,487/187,558,154) to 6.40% (12,009,307/187,558,154). The annual percent change (APC) for the complaint topic was 48.80% (P<.001) for 2011 to 2014 and -16.82% (P<.001) for 2014 to 2020. The APC for the inquiry topic was 16.21% (P=.41) for 2011 to 2014 and -11.00% (P<.001) for 2014 to 2020. For the prognosis topic, the annual APC was 11.18% (P<.001) for 2011 to 2017 and -19.86% (P<.001) for 2017 to 2020. For the treatment topic, the annual APC was 14.04% (P<.001) for 2011 to 2016 and -38.83% (P<.001) for 2016 to 2020. The age distribution of those searching for topics related to PE showed that the population aged 20 to 40 years comprised nearly 70% of the total search inquiries (second was 17.95% in the age group younger than 19 years). People from East China made over 50% of the total search queries. The fluctuating online popularity of PE searches reflects the real-time population demands. It may help medical professionals better understand population interest, population concerns, regional variations, and gender differences on a nationwide scale and make disease-specific health care policies. The internet search data could be more reliable when the insufficient and lagging registry data are completed.


Development of a staff recall system for mass casualty incidents using cell phone text messaging.
After a mass casualty incident (MCI), rapid mobilization of hospital personnel is required because of an expected surge of victims. Risk assessment of our department's manual phone tree recall system revealed multiple weaknesses that would limit an effective response. Because cell phone use is widespread within the department, we developed and tested a staff recall system, based in our anesthesia information management system (AIMS), using Short Message Service (SMS) text messaging. We sent test text messages to anesthesia staff members' cell phone numbers, determined the distance from their home to the hospital, and stored this information in our AIMS. Latency testing for the time from transmission of SMS test messages from the server to return of an e-mail reply was determined at 2 different times on 2 different dates, 1 of which was a busy holiday weekend, using volunteers within the department. Two unannounced simulated disaster recall drills were conducted, with text messages sent asking for the anticipated time to return to the hospital. A timeline of available staff on site was determined. Reasons for failure to respond to the disaster notification message were tabulated. Latency data were fit by a log-normal distribution with an average of 82 seconds from message transmission to e-mail reply. Replies to the simulated disaster alert were received from approximately 50% of staff, with 16 projecting that they would have been able to be back at the hospital within 30 minutes on both dates. There would have been 21 and 23 staff in-house at 30 minutes, and 32 and 37 staff in-house at 60 minutes on the first and second test date, respectively, including in-house staff. Of the nonresponders to the alert, 48% indicated that their cell phone was not with them or was turned off, whereas 22% missed the message. Our SMS staff recall system is likely to be able to rapidly mobilize sufficient numbers of anesthesia personnel in response to an MCI, but actual performance cannot be predicted with confidence. Using our AIMS as the source for contact information and from which to send messages was simple, inexpensive, and easy to implement. Updating contact information, periodic testing, and analysis of responses to simulated disaster alerts are essential for the effective functioning of such a system. However, maintenance of alternative methods of communication is recommended, because there may be more significant message transmission delays and failures during an actual MCI, and not all staff will receive the text message in a timely fashion.


Roles of differently polarized macrophages in the initiation and progressionof pancreatic cancer.
During development of pancreatic cancer macrophage-mediated inflammatory processes and the formation of cancerous lesions are tightly connected. Based on insight from mouse models we provide an overview on the functions of classically-activated pro-inflammatory and alternatively-activated anti-inflammatory macrophages in the initiation and progression of pancreatic cancer. We highlight their roles in earliest events of tumor initiation such as acinar-to-ductal metaplasia (ADM), organization of the fibrotic lesion microenvironment, and growth of low-grade (LG) lesions. We then discuss their roles as tumor-associated macrophages (TAM) in progression to high-grade (HG) lesions with a cancerous invasive phenotype and an immunosuppressive microenvironment. Another focus is on how targeting these macrophage populations can affect immunosuppression, fibrosis and responses to chemotherapy, and eventually how this knowledge could be used for novel therapy approaches for patients with pancreatic ductal adenocarcinoma (PDA).


Dietary essential fatty acids and brain function: a developmental perspective on mechanisms.
Brain development is a complex interactive process in which early disruptive events can have long-lasting effects on later functional adaptation. It is a process that is dependent on the timely orchestration of external and internal inputs through sophisticated intra- and intercellular signalling pathways. Long-chain polyunsaturated fatty acids (LCPUFA), specifically arachidonic acid and docosahexaenoic acid (DHA), accrue rapidly in the grey matter of the brain during development, and brain fatty acid (FA) composition reflects dietary availability. Membrane lipid components can influence signal transduction cascades in various ways, which in the case of LCPUFA include the important regulatory functions mediated by the eicosanoids, and extend to long-term regulation through effects on gene transcription. Our work indicates that FA imbalance as well as specific FA deficiencies can affect development adversely, including the ability to respond to environmental stimulation. For example, although the impaired water-maze performance of mice fed a saturated-fat diet improved in response to early environmental enrichment, the brains of these animals showed less complex patterns of dendritic branching. Dietary n-3 FA deficiency influences specific neurotransmitter systems, particularly the dopamine systems of the frontal cortex. We showed that dietary deficiency of n-3 FA impaired the performance of rats on delayed matching-to-place in the water maze, a task of the type associated with prefrontal dopamine function. We did not, however, find an association over a wider range of brain DHA levels and performance on this task. Some, but not all, studies of human infants suggest that dietary DHA may play a role in cognitive development as well as in some neurodevelopmental disorders; this possibility has important implications for population health.


Mesenteric ischemia.
Diagnosis of acute mesenteric ischemia in the early stages is now possible with modern computed tomography (CT), using intravenous contrast enhancement and imaging in the arterial and/or portal venous phase. The availability of CT around the clock means that more patients with acute mesenteric ischemia may be treated with urgent intestinal revascularization. The establishment of a hybrid operation room is most important to be able to perform explorative laparotomy for evaluation of the extent of mesenteric ischemia and successful intestinal revascularization. Endovascular recanalization and stenting has become an important alternative, especially in patients with both acute and chronic thrombotic superior mesenteric artery (SMA) occlusion. Aspiration embolectomy, thrombolysis and open surgical embolectomy, followed by on-table angiography, are the treatment options for embolic SMA occlusion. Endovascular therapy may be an option in the few patients with mesenteric venous thrombosis who do not respond to anticoagulation therapy. The concept of damage-control surgery is recommended after intestinal revascularization. Intestinal revascularization in patients with arterial occlusive mesenteric ischemia reduces bowel morbidity and mortality. Observational studies report that both endovascular and open vascular therapy options are effective, but endovascular technique may be preferred in these often elderly and fragile patients.


Loss of autonomy of hospitalized elderly patients: does hospitalization increase disability?
The study of the determinants of loss of autonomy during hospitalization may be valuable in the identification of the most effective interventions and to achieve better outcomes. The aim of this study was to describe changes in the level of autonomy of the elderly admitted to the hospital at the entrance and at discharge in relation to a rehabilitation program. Prospective observational study conducted at the INRCA Geriatric Hospital of Ancona. The study included patients aged 65 years and over, daily admitted to INRCA Hospital of Ancona between September and December 2010. Criteria for inclusion were age ≥ 65 years, length of stay > 24 hours and signed informed consent. Patients admitted for less than 24 hours or in day hospital or day surgery were excluded from the beginning. A total of 1266 elderly patients were recruited in the period. From this sample, 74 people who died during hospitalization were excluded. At the time of hospitalization (within 24 hours) and at discharge, patients were evaluated with the Barthel Index (BI), the Rankin scale, and a short assessment of cognitive status derived from the Mini Mental State Examination (MMSE). Referring to 1192 subjects who participated to the study, the mean age was 82.13 years ±7.39, age range between 65 and 100 years. The average BI was 56.6±36.16 (SD) (median value =60) at admission and 63.84±34.7 (SD) (median value=70) at discharge. The average Rankin score at admission was 2.63±1.5 (SD) (median value=3). Patients presented better score of the BI at discharge and this figure was associated to the implementation of a rehabilitation treatment. Hospitalization of the elderly patient in a suitable environment, such as a geriatric hospital, contrary to some theories highlighting only the negative aspects of removal from the living environment, can be a measure of benefit for the reduction of disability and the recovery of compromised activities along and after the acute event. The collection of data on the level of autonomy of the subjects before and after hospitalization can be a useful element for clinical evaluation in a geriatric hospital.


Decision aid for women considering breast cancer screening.
The aim of this study was to describe the process and challenges of developing a decision aid for the national public breast cancer screening program in Finland. An expert team with stakeholder representation used European guidelines and other literature as basis for selecting relevant content and format for the decision aid for breast cancer screening. Feedback from women was sought for the draft documents. A decision aid attached to the invitation letter for screening was considered the best way to ensure access to information. In addition, tailored letter templates for all phases of the screening program, a poster, and a public website were developed. Initial feedback from users (women, professionals, and service providers), was mainly positive. Six months after publishing, the implementation of the decision aid was still incomplete. Providing balanced information for women invited to breast cancer screening is demanding and requires careful planning. Professionals and service providers need to be engaged in the HTA process to ensure proper dissemination and implementation of the information. End user participation is essential in the formulation of information. There is a need to follow up the implementation of the decision aid.


Bronchoscopy with transbronchial biopsies: measurement of bleeding volume and evaluation of the predictive value of coagulation tests.
The objectives of this study were to measure the bleeding volume associated with fibreoptic bronchoscopy with transbronchial biopsies (TBB), to correlate it with coagulation tests and to compare bleeding volume in patients with and without lung transplant. A total of 104 consecutive TBB in 51 different patients was evaluated prospectively. Before each procedure, haemoglobin, blood platelets, prothrombin time (PT), activated partial thromboplastin time (aPTT) and bleeding time were measured. During the procedure, lavage fluid and blood were collected by suction. The haemoglobin concentration of the mixture was measured and bleeding volume was calculated. Clinically significant bleeding was arbitrarily defined as >20 mL blood present in lavage fluid. The mean+/-SD bleeding volume was 7+/-10 mL with no statistically significant difference between transplanted and nontransplanted patients. In eight procedures (7.7%) the bleeding volume was >20 mL (range 22-61 mL). Prebiopsy values for blood platelet counts, PT and aPTT did not predict a bleeding tendency in any of the procedures in which significant bleeding occurred. No correlation was found between bleeding time and bleeding volume in the 17 procedures performed in patients with a prolonged bleeding time (> or =10 min). The bleeding associated with transbronchial biopsies was usually minor and quantitatively similar in patients with or without lung transplant. Coagulation tests could not predict clinically significant bleeding, which may occur in patients with normal coagulation test results.


The interpretation of systemic arterial blood pressure. Part III: hypertension retinopathy.
Systemic blood pressure is a vital sign and fundamental variable and as such the areas of its involvement in all individuals are indeed multifaceted. The purpose of this paper is to discuss the interpretation of systemic blood pressure readings as they specifically relate to a detailed analysis of hypertensive retinopathy.


Association between duration of tirofiban therapy before percutaneous intervention and tissue level perfusion (a TACTICS-TIMI 18 substudy).
In the setting of acute coronary syndromes, thrombotic embolization and activation of platelets with release of vasoconstrictors into the downstream microvasculature may occur before cardiac catheterization. In the Treat Angina with tirofiban and determine Cost of Therapy with an Invasive or Conservative Strategy-Thrombolysis In Myocardial Infarction 18 (TACTICS-TIMI 18) trial angiographic substudy, a shorter duration of tirofiban infusion before percutaneous coronary intervention was associated with impaired myocardial perfusion before and after intervention.


Dexmedetomidine Withdrawal Syndrome in Children in the PICU: Systematic Review and Meta-Analysis.
To systematically review literature describing the clinical presentation, risk factors, and treatment for dexmedetomidine withdrawal in the PICU (PROSPERO: CRD42022307178). MEDLINE/PubMed, Cochrane, Web of Science, and Scopus databases were searched. Eligible studies were published from January 2000 to January 2022 and reported clinical data for patients younger than 21 years old following discontinuation of dexmedetomidine after greater than or equal to 24 hours of infusion. Abstracts identified during an initial search were screened and data were manually abstracted after full-text review of eligible articles. The Newcastle-Ottawa Scale was used to assess study quality. Summary statistics were provided and Spearman rank correlation coefficient was used to identify relationships between covariates and withdrawal signs. A weighted prevalence for each withdrawal sign was generated using a random-effects model. Twenty-three studies (22 of which were retrospective cohort studies) containing 28 distinct cohorts were included. Median cumulative dexmedetomidine exposure by dose was 105.95 μg/kg (range, 30-232.7 μg/kg), median dexmedetomidine infusion duration was 131.75 hours (range, 20.5-525.6 hr). Weighted estimates for proportion (95% CI) of subjects experiencing withdrawal signs across all cohorts were: hypertension 0.34 (range, 0.0-0.92), tachycardia 0.26 (range, 0.0-0.87), and agitation 0.26 (range, 0.09-0.77). Meta-analysis revealed no correlation between dexmedetomidine exposure variables and withdrawal signs. A moderate negative monotonic relationship existed between the proportion of patients who had undergone cardiac surgery and the proportion experiencing hypertension (correlation coefficient, -0.47; p = 0.048) and tachycardia (correlation coefficient, -0.57; p = 0.008), indicating that in cohorts with a higher proportion of patients who were postcardiac surgery, there were fewer occurrences of hypertension and or tachycardia. On review of the 2000-2022 literature, dexmedetomidine withdrawal may be characterized by tachycardia, hypertension, or agitation, particularly with higher cumulative doses or prolonged durations. Since most studies included in the review were retrospective, prospective studies are needed to further clarify risk factors, establish diagnostic criteria, and identify optimal management strategies.


Genetic architecture influences when and how hybridization contributes to colonization.
The role of genetic architecture in adaptation to novel environments has received considerable attention when the source of adaptive variation is de novo mutation. Relatively less is known when the source of adaptive variation is inter- or intraspecific hybridization. We model hybridization between divergent source populations and subsequent colonization of an unoccupied novel environment using individual-based simulations to understand the influence of genetic architecture on the timing of colonization and the mode of adaptation. We find that two distinct categories of genetic architecture facilitate rapid colonization but that they do so in qualitatively different ways. For few and/or tightly linked loci, the mode of adaptation is via the recovery of adaptive parental genotypes. With many unlinked loci, the mode of adaptation is via the generation of novel hybrid genotypes. The first category results in the shortest colonization lag phases across the widest range of parameter space, but further adaptation is mutation limited. The second category takes longer and is more sensitive to genetic variance and dispersal rate, but can facilitate adaptation to environmental conditions that exceed the tolerance of parental populations. These findings have implications for understanding the origins of biological invasions and the success of hybrid populations.


Mercury methylation by metabolically versatile and cosmopolitan marine bacteria.
Microbes transform aqueous mercury (Hg) into methylmercury (MeHg), a potent neurotoxin that accumulates in terrestrial and marine food webs, with potential impacts on human health. This process requires the gene pair hgcAB, which encodes for proteins that actuate Hg methylation, and has been well described for anoxic environments. However, recent studies report potential MeHg formation in suboxic seawater, although the microorganisms involved remain poorly understood. In this study, we conducted large-scale multi-omic analyses to search for putative microbial Hg methylators along defined redox gradients in Saanich Inlet, British Columbia, a model natural ecosystem with previously measured Hg and MeHg concentration profiles. Analysis of gene expression profiles along the redoxcline identified several putative Hg methylating microbial groups, including Calditrichaeota, SAR324 and Marinimicrobia, with the last the most active based on hgc transcription levels. Marinimicrobia hgc genes were identified from multiple publicly available marine metagenomes, consistent with a potential key role in marine Hg methylation. Computational homology modelling predicts that Marinimicrobia HgcAB proteins contain the highly conserved amino acid sites and folding structures required for functional Hg methylation. Furthermore, a number of terminal oxidases from aerobic respiratory chains were associated with several putative novel Hg methylators. Our findings thus reveal potential novel marine Hg-methylating microorganisms with a greater oxygen tolerance and broader habitat range than previously recognized.


Monoterpenes released from fruit, plant, and vegetable systems.
To quantify the emission rate of monoterpenes (MTs) from diverse natural sources, the sorbent tube (ST)-thermal desorption (TD) method was employed to conduct the collection and subsequent detection of MTs by gas chromatography. The calibration of MTs, when made by both mass spectrometric (MS) and flame ionization detector (FID), consistently exhibited high coefficient of determination values (R2 > 0.99). This approach was employed to measure their emission rate from different fruit/plant/vegetable (F/P/V) samples with the aid of an impinger-based dynamic headspace sampling system. The results obtained from 10 samples (consisting of carrot, pine needle (P. sylvestris), tangerine, tangerine peel, strawberry, sepals of strawberry, plum, apple, apple peel, and orange juice) marked α-pinene, β-pinene, myrcene, α-terpinene, R-limonene, γ-terpinene, and p-cymene as the most common MTs. R-limonene was the major species emitted from citrus fruits and beverages with its abundance exceeding 90%. In contrast, α-pinene was the most abundant MT (37%) for carrot, while it was myrcene (31%) for pine needle. The overall results for F/P/V samples confirmed α-pinene, β-pinene, myrcene, α-terpinene, and γ-terpinene as common MTs. Nonetheless, the types and magnitude of MTs released from fruits were distinguished from those of vegetables and plants.


Multi-organ abnormalities and mTORC1 activation in zebrafish model of multiple acyl-CoA dehydrogenase deficiency.
Multiple Acyl-CoA Dehydrogenase Deficiency (MADD) is a severe mitochondrial disorder featuring multi-organ dysfunction. Mutations in either the ETFA, ETFB, and ETFDH genes can cause MADD but very little is known about disease specific mechanisms due to a paucity of animal models. We report a novel zebrafish mutant dark xavier (dxa(vu463) ) that has an inactivating mutation in the etfa gene. dxa(vu463) recapitulates numerous pathological and biochemical features seen in patients with MADD including brain, liver, and kidney disease. Similar to children with MADD, homozygote mutant dxa(vu463) zebrafish have a spectrum of phenotypes ranging from moderate to severe. Interestingly, excessive maternal feeding significantly exacerbated the phenotype. Homozygous mutant dxa(vu463) zebrafish have swollen and hyperplastic neural progenitor cells, hepatocytes and kidney tubule cells as well as elevations in triacylglycerol, cerebroside sulfate and cholesterol levels. Their mitochondria were also greatly enlarged, lacked normal cristae, and were dysfunctional. We also found increased signaling of the mechanistic target of rapamycin complex 1 (mTORC1) with enlarged cell size and proliferation. Treatment with rapamycin partially reversed these abnormalities. Our results indicate that etfa gene function is remarkably conserved in zebrafish as compared to humans with highly similar pathological, biochemical abnormalities to those reported in children with MADD. Altered mTORC1 signaling and maternal nutritional status may play critical roles in MADD disease progression and suggest novel treatment approaches that may ameliorate disease severity.


Clinical Significance of BCL2, C-MYC, and BCL6 Genetic Abnormalities, Epstein-Barr Virus Infection, CD5 Protein Expression, Germinal Center B Cell/Non-Germinal Center B-Cell Subtypes, Co-expression of MYC/BCL2 Proteins and Co-expression of MYC/BCL2/BCL6 Proteins in Diffuse Large B-Cell Lymphoma: A Clinical and Pathological Correlation Study of 120 Patients.
Background: Clinical significance of germinal center B-cell (GCB) and non-GCB sub-categorization, expression of MYC, BCL2, BCL6, CD5 proteins and Epstein Barr virus encoded RNA (EBER) positivity in diffuse large B-cell lymphoma (DLBCL) remain controversial. Could these biomarkers accurately identify high risk DLBCL patients? Are MYC, BCL2 and BCL6 proteins expression feasible as baseline testing to predict c-Myc, BCL2 or BCL6 gene rearrangements? Aims: To investigate prognostic values of GCB/non-GCB sub-categorization, Double Protein Expression Lymphoma (DPL), Triple Protein Expression Lymphoma (TPL), positivity of CD5 protein and EBER in patients with DLBCL disease. To evaluate correlation between BCL2 , c-Myc and BCL6 gene rearrangements with BCL2, MYC and BCL6 proteins expression. Methods: Diagnostic tissue samples of 120 DLBCL patients between January 2012 to December 2013 from four major hospitals in Malaysia were selected. Samples were subjected to immunohistochemical staining, fluorescent in-situ hybridization (FISH) testing, and central pathological review. Pathological data were correlated with clinical characteristics and treatment outcome. Results: A total of 120 cases were analysed. Mean age of diagnosis was 54.1 years ± 14.6, 64 were males, 56 were females, mean follow up period was 25 months (ranged from 1 to 36 months). Of the 120 cases, 74.2% were non-GCB whereas 25.8% were GCB, 6.7% were EBER positive, 6.7% expressed CD5 protein, 13.3% were DPL and 40% were TPL. The prevalence of c-Myc, BCL2, BCL6 gene rearrangements were 5.8%, 5.8%, and 14.2%, respectively; and 1.6% were Double Hit Lymphoma (DHL). EBER positivity, DPL, TPL, c-Myc gene rearrangement, BCL2 gene rearrangement, extra copies of BCL2 gene and BCL6 gene rearrangement were associated with shorter median overall survival (P<0.05). IPI score was the significant determinants of median overall survival in DPL and TPL (P<0.05). CD5 protein expression and GCB/non-GCB sub-categorization did not affect treatment outcome (P>0.05). Overall, c-Myc, BCL2 and BCL6 gene rearrangements showed weak correlation with expression of MYC, BCL2 and BCL6 proteins (P>0.05). Fluorescent in situ hybridization is the preferred technique for prediction of treatment outcome in DLBCL patients. Conclusion: c-Myc, BCL2, and BCL6 gene rearrangements, EBER expression, DHL, TPL and IPI score are reliable risk stratification tools. MYC, BCL2 and BCL6 proteins expression are not applicable as baseline biomarkers to predict c-Myc, BCL2, and BCL6 gene rearrangements.


Characterization of Desulfovibrio biadhensis sp. nov., isolated from a thermal spring.
A novel anaerobic, mesophilic, slightly halophilic sulfate-reducing bacterium, designated strain Khaled BD4(T), was isolated from waters of a Tunisian thermal spring. Cells were vibrio-shaped or sigmoids (5-7×1-1.5 µm) and occurred singly or in pairs. Strain Khaled BD4(T) was Gram-stain-negative, motile and non-sporulated. It grew at 25-45 °C (optimum 37 °C), at pH 5.5-8.3 (optimum pH 7.0) and with 0.5-8% NaCl (optimum 3%). It required vitamins or yeast extract for growth. Sulfate, thiosulfate, sulfite and elemental sulfur served as terminal electron acceptors, but not fumarate, nitrate or nitrite. Strain Khaled BD4(T) utilized H2 in the presence of 2 mM acetate (carbon source), but also lactate, formate, pyruvate and fumarate in the presence of sulfate. Lactate was incompletely oxidized to acetate. Amongst substrates used, only pyruvate was fermented. Desulfoviridin and c-type cytochrome were present. The G+C content of the DNA was 54.6 mol%. The main fatty acids were anteiso -C(15 : 0), iso-C(18 : 0), iso-C(17 : 0) and iso-C(14 : 0). Phylogenetic analysis of the 16S rRNA gene sequence indicated that strain Khaled BD4(T) had Desulfovibrio giganteus DSM 4123(T) (96.7% similarity) as its closest phylogenetic relative. On the basis of 16S rRNA gene sequence comparisons together with genetic and physiological characteristics, strain Khaled BD4(T) is assigned to a novel bacterial species, for which the name Desulfovibrio biadhensis sp. nov. is proposed. The type strain is Khaled BD4(T) ( = DSM 28904(T) = JCM 30146(T)).


[Early diagnosis and prognosis of bacterial tubulo-interstitial nephritis in children].
The authors provide the data of a prospective follow-up of children with diseases of the urinary system organs. Analysis was made of the role of endogenous and exogenous factors in the formation of abacterial and bacterial tubulointerstitial nephritis (TIN) in children with predisposing conditions. It has been established that progression of the tubulointerstitial process can be seen in patients infected with causative agents capable of intracellular parasitizing and persistence in the body. Depending on the intensity of membranopathological and immune disorders the clinicopathogenetic manifestations of different stages of TIN are described in detail. It is shown that there is a possibility of early diagnosis of the bacterial stage of the disease on the basis of detecting the persistent microflora according to an assay of the antilysozyme activity of the causative agent and the urine content of beta-lysines in urine. The authors base the necessity of the preventive treatment of children with predisposing conditions and abacterial TIN to avert the formation and progression of bacterial TIN by means of agents that may prevent the persistence of causative agents and raising the efficacy of antiinfectious defence of the macroorganism.


Development of a novel molecular tool to study molecular ecology of Ornithomya (Hippoboscidae) avian louse flies.
Louse flies (Diptera: Hippoboscidae) are obligatory hematophagous ectoparasites of birds and mammals. These widely distributed parasitic flies may have a significant impact on wild and farm animals by feeding on their blood and transmitting bloodborne pathogens. However, despite their ecological importance, louse flies are clearly underrepresented in host-parasite research and implementation of genetic approaches in this group is generally hampered by lacking molecular tools. In addition, louse flies that parasitize long-distance migrants can travel long distances with their avian hosts, facilitating the large-scale spread of pathogens across landscapes and geographic regions. Given the wide diversity of louse flies that parasitize a variety of avian hosts, their direct negative impact on host survival, and their high potential to transmit bloodborne pathogens even along avian migration routes, it is surprising that our knowledge of louse fly ecology is rather modest and incomplete. Here, we aimed to develop a novel molecular tool for polyxenous avian louse flies from the genus Ornithomya, which are among the most common and widely distributed representatives of Hippoboscidae family, to improve research of their genetic population structure and molecular ecology. Using the Illumina Mi-seq sequencing, we conducted a genome-wide scan in Ornithomya avicularia to identify putative microsatellite markers. A panel of 26 markers was selected to develop amplification protocols and assess polymorphism in the Central European population of O. avicularia, as well as to test for cross-amplification in a congeneric species (O. chloropus). A genome-scan in O. avicularia identified over 12 thousand putative microsatellite markers. Among 26 markers selected for a population-wide screening; one did not amplify successfully and three were monomorphic. 22 markers were polymorphic with at least two alleles detected. Two markers showed presence of null alleles. A cross-amplification of microsatellite markers in O. chloropus revealed allelic polymorphism at 14 loci, with the mean allelic richness of 3.78 alleles per locus (range: 2-8). Our genome-wide scan in O. avicularia provides a novel and powerful tool for molecular research in Ornithomya louse flies. Our panel of polymorphic microsatellite loci should allow genotyping of louse flies from geographically distinct populations and from a wide spectrum of avian hosts, enhancing population genetic and phylogeographic research in Ornithomya.


Serum from CCl4-induced acute rat injury model induces differentiation of ADSCs towards hepatic cells and reduces liver fibrosis.
Cellular therapies hold promise to alleviate liver diseases. This study explored the potential of allogenic serum isolated from rat with acute CCl4 injury to differentiate adipose derived stem cells (ADSCs) towards hepatic lineage. Acute liver injury was induced by CCl4 which caused significant increase in serum levels of VEGF, SDF1α and EGF. ADSCs were preconditioned with 3% serum isolated from normal and acute liver injury models. ADSCs showed enhanced expression of hepatic markers (AFP, albumin, CK8 and CK19). These differentiated ADSCs were transplanted intra-hepatically in CCl4-induced liver fibrosis model. After one month of transplantation, fibrosis and liver functions (alkaline phosphatase, ALAT and bilirubin) showed marked improvement in acute injury group. Elevated expression of hepatic (AFP, albumin, CK 18 and HNF4a) and pro survival markers (PCNA and VEGF) and improvement in liver architecture as deduced from results of alpha smooth muscle actin, Sirius red and Masson's trichome staining was observed.


Bumblebee ocelli and navigation at dusk.
Western bumblebees fly straight while homing by polarized light, but zigzag when they use landmarks. That flight difference was used to determine the roles of the dorsal ocelli and parts of the compound eyes in homing. Polarized light and ocelli can prolong foraging at twilight, when landmarks are no longer visible.


[Effects of xenotransplantation of pancreatic islet cells on immunological state of patients with diabetic angiopathies].
The cell and humoral immunity state was studied up in 35 patients with diabetic angiopathy (insulin-dependent diabetes mellitus) before and 7 days, 3, 6, 9 and 12 months after the pancreatic islet cells (PIC) xenotransplantation conduction in newborn piglets. Stimulation or suppression of the recipient immune system were not observed. This is associated with the PIC immune modulation due to their cultivation. Transplantation of the newborn piglets PIC is a safe method concerning the recipient immune system state. The contents of antibodies to insulin do not change in term of observation up to one year after the PIC cultures xenotransplantation conduction.


Insulin Autoimmune Syndrome possibly caused by alpha lipoic acid.
Insulin Autoimmune Syndrome (IAS) is a rare disease characterized by hypoglycemia and autoantibodies to insulin without prior insulin administration. Here, we report a case of IAS associated with alpha lipoic acid (ALA). The patient is a 55-year-old man. He began to complain of hypoglycemic symptoms after taking ALA. He lost consciousness in the late postprandial period and blood glucose was found to be 27 mg/dl. A high insulin level and high titers of insulin antibodies were detected. His HLA genotype contains DRB1* 0406. As ALA comes to be used widely, the incidence of IAS due to ALA might increase.


Implementation of the peer-led team-learning instructional model as a stopgap measure improves student achievement for students opting out of laboratory.
In entry-level university courses in science, technology, engineering, and mathematics fields, students participating in associated laboratory sessions generally do better than those who have no related lab classes. This is a problem when, for various reasons, not enough lab sections can be offered for students and/or when students opt out of optional available lab courses. Faced with such a situation, this study evaluated the efficacy of the peer-led team-learning (PLTL) instructional model as a potential method for narrowing the achievement gap among undergraduate students electing not to enroll in an optional laboratory component of an introductory biology course. In peer-led workshops, small groups of students participated in solving problems and other activities that encouraged active learning. Students led by peer leaders attained significantly higher exam and final course grades in introductory biology than comparable students not participating in PLTL. Among the introductory biology students who opted not to enroll in the optional lab course, those who participated in PLTL averaged more than a letter grade higher than those who did not. This difference was statistically significant, and the PLTL workshops almost entirely closed the achievement gap in lecture exam and final grades for students who did not take the lab.


[Lymphoma and the urogenital system: apropos of a case].
Lymphomas constitute a group of malignant lymphoreticular diseases that may affect the adrenal glands and the GU system as a primary condition or, more frequently, as distant invasion. We report on a case of diffuse, histiocytic non-Hodgkin lymphoma that had been in hematologic clinical remission but had recurred with invasion of the right renal parenchyma. Initially, it could not be determined whether it was a primary neoplasm or the result of primary lymphatic spread. The reports published in the literature relative to this condition are reviewed.


Developmental underpinnings of differences in rodent novelty-seeking and emotional reactivity.
Innate differences in human temperament strongly influence how individuals cope with stress and also predispose towards specific types of psychopathology. The present study examines the developing brain in an animal model of temperamental differences to examine how altered neurodevelopment may engender differences in emotional reactivity that are stable throughout the animal's life. We utilize selectively-bred High Responder (bHR) and Low Responder (bLR) rats that exhibit dramatic emotional behavior differences, with bHRs exhibiting exaggerated novelty-exploration, aggression, impulsivity and drug self-administration, and bLRs showing marked behavioral inhibition and exaggerated anxiety-like and depressive-like behavior. Using Affymetrix microarrays, we assessed bLR and bHR gene expression in the developing brain on postnatal days (P)7, 14 and 21, focusing on the hippocampus and nucleus accumbens, two regions related to emotionality and known to differ in adult bLR and bHR rats. We found dramatic gene expression differences between bLR and bHR in the P7 and P14 hippocampus, with minimal differences in the nucleus accumbens. Some of the most profound differences involved genes critical for neurodevelopment and synaptogenesis. Stereological studies evaluated hippocampal structure in developing bHR and bLR pups, revealing enhanced hippocampal volume and cell proliferation in bLR animals. Finally, behavioral studies showed that the characteristic bHR and bLR behavioral phenotypes emerge very early in life, with exploratory differences apparent at P16 and anxiety differences present by P25. Together these data point to specific brain regions and critical periods when the bHR and bLR phenotypes begin to diverge, which may eventually allow us to test possible therapeutic interventions to normalize extreme phenotypes (e.g. the anxiety-prone nature of bLRs or drug addiction proclivity of bHRs).


Toxicity study of an antidipsotropic Chinese herbal mixture in rats: NPI-028.
To determine the potential toxicity and safety of the Chinese herbal medicine NPI-028 in rats following subchronic (3-month) exposure via daily oral consumption. Subchronic toxicity was evaluated in four groups of rats (n = 10 per group) receiving NPI-028 orally at a dose of either 0.0 (normal diet control), 0.5, 1.0, or 2.0 g/kg, ingested as part of their daily diet for 3 months. NPI-028 was incorporated into powdered rat chow diet as a specific percent of the total diet provided each day. The primary active isoflavone content of NPI-028 (puerarin) used in the rat diet was also determined. Subchronic toxicity was assessed over a 3-month period by biweekly measurement of water and food intake, weight gain, and visual inspection for maintenance of grooming and normal behavior. At the end of the study period rats were euthanized and blood was obtained for hematologic and chemical analysis. Organs were removed for histopathologic examination. Rats in all three NPI-028 dose groups were similar to the control group in weight gain, food intake, and water intake over the study period. Hematology, blood chemistries, and organ histology in rats at all three NPI-028 doses did not significantly differ from control rats. Minor exceptions were elevated urea nitrogen values at all NPI-028 doses, and increased triglyceride and thyroid-stimulating hormone values in the lowest NPI-028 dose-treated group. Puerarin (used as a dietary isoflavone marker) content of NPI-028 was 26 mg/g dry weight. NPI-028 ingested orally at doses up to 2.0 g/kg per day in the rat diet for up to 3 months resulted in normal growth with no changes in hematologic or hepatic parameters, and only minor alterations in renal and blood chemistry parameters. There was no evidence of abnormal histology. These data suggest the long-term daily oral consumption of NPI-028 as a part of the daily diet for 3 months, at the doses studied, is safe in rats. Thus, NPI-028 may potentially be safe for clinical use as an antidipsotropic agent.


Reversion and conversion of Mycobacterium tuberculosis IFN-gamma ELISpot results during anti-tuberculous treatment in HIV-infected children.
Recent interest has focused on the potential use of serial interferon gamma (IFN-gamma) release assay (IGRA) measurements to assess the response to anti-tuberculous (TB) treatment. The kinetics of IFN-gamma responses to Mycobacterium tuberculosis (MTB) antigens in HIV-infected children during treatment have not however been previously investigated. IFN-gamma responses to the MTB antigens, ESAT-6, CFP-10 and PPD were measured by an enzyme-linked immunospot assay (IFN-gamma ELISpot) at presentation and at one, two and six months after starting anti-tuberculous treatment in HIV-infected children with definite or probable TB. Responses at different time points were compared using a Mann-Whitney U test with paired data analysed using the Wilcoxon signed rank test. A Fisher's exact or Chi-squared test was used to compare proportions when test results were analysed as dichotomous outcomes. Of 102 children with suspected TB, 22 (21%) had definite TB and 24 (23%) probable TB. At least one follow up IFN-gamma ELISpot assay result was available for 31 (67%) of the 46 children. In children with definite or probable TB in whom the IFN-gamma ELISpot assay result was positive at presentation, anti-tuberculous treatment was accompanied by a significant decrease in both the magnitude of the IFN-gamma response to individual or combined MTB-specific antigens (ESAT-6 median 110 SFCs/106 PBMC (IQR 65-305) at presentation vs. 15 (10-115) at six months, p = 0.04; CFP-10 177 (48-508) vs. 20 (5-165), p = 0.004, ESAT-6 or CFP-10 median 250 SFCs/106 PBMC (IQR 94-508) vs. 25 (10-165), p = 0.004) and in the proportion of children with a positive IFN-gamma ELISpot assay (Fisher's exact test: ESAT-6 15/0 vs 5/11, p = 0.0002, CFP-10 22/0 vs 8/17, p = 0.0001, ESAT-6 or CFP-10 22/0 vs. 9/17, p= 0.002). However almost half of the children had a positive IFN-gamma ELISpot assay after six months of anti-tuberculous treatment. In addition, there was conversion of the IFN-gamma ELISpot assay result during anti-tuberculous therapy in six of 12 children in whom the initial IFN-gamma ELISpot assay was negative. In HIV-infected children with definite or probable TB, anti-tuberculosis treatment is accompanied by a reduction in the magnitude of the IFN-gamma ELISpot response to MTB-antigens. However, serial IFN-gamma ELISpot measurements appear to have limited clinical utility in assessing a successful response to anti-tuberculous treatment in HIV infected children.


Label-free impedimetric immunoassay for trace levels of polychlorinated biphenyls in insulating oil.
A rapid, ultrasensitive, and practical label-free impedimetric immunoassay for measuring trace levels of total polychlorinated biphenyls (PCBs) in insulating oil was developed. First, we developed a novel monoclonal antibody (RU6F9) for PCBs by using a designed immunogen and characterized its binding affinity for a commercial mixtures of PCBs and its main congeners. A micro comblike gold electrode was fabricated, and the antibody was covalently immobilized on the electrode through a self-assembled monolayer formed by dithiobis-N-succinimidyl propionate. The antigen-binding event on the surface of the functionalized electrode was determined as the change in charge transfer resistance by using electrochemical impedance spectroscopy. The resulting impedimetric immunoassay in aqueous solution achieved a wide determination range (0.01-10 μg/L) and a low detection limit (LOD) of 0.001 μg/L, which was 100-fold more sensitive than a conventional flow-based immunoassay for PCBs. By combining the impedimetric immunoassay with a cleanup procedure for insulating oil utilizing a multilayer cleanup column followed by DMSO partitioning, an LOD of 0.052 mg/kg-oil was achieved, which satisfied the Japanese regulation criterion of 0.5 mg/kg-oil. Finally, the immunoassay was employed to determine total PCB levels in actual used insulating oils (n = 33) sampled from a used transformer containing trace levels of PCBs, and the results agreed well with the Japanese official method (HRGC/HRMS).


Comparative study of adhesion molecule expression in nodular lesions of Behçet syndrome and other forms of panniculitis.
Adhesion molecules have a role in many vasculitic disorders. Our aim was to evaluate the status of adhesion molecules in nodular lesions of Behçet syndrome (BS) and compare them with results for the 2 most common types of panniculitis, erythema nodosum (EN) and nodular vasculitis (NV). We included the data for 28 patients with nodular lesions of BS, 24 with EN, and 22 with NV. A panel of monoclonal antibodies against E-selectin, P-selectin, vascular cell adhesion molecule-1, platelet endothelial cell adhesion molecule-1, and intercellular adhesion molecule (ICAM)-1 were applied. The distribution and intensity of adhesion molecules were assessed. There were no statistically significant differences between the BS and control groups in regard to these adhesion molecules except for ICAM-1. The percentage of strongly ICAM-1-stained endothelial cells in subcutaneous fat tissue in relation to the total number of endothelial cells was the lowest in BS (P= .0208). Because many lesions of BS were related to an enhanced inflammatory response, the lower percentage of ICAM-1 expression seems counterintuitive.


Covalently surface-grafting α‑zirconium phosphate nanoplatelets enables collagen fiber matrix with ultraviolet barrier, antibacterial, and flame-retardant properties.
Manipulating the dispersibility and reactivity of two-dimensional nanomaterials in collagen fibers (CFs) matrix has aroused attention in the fabrication of multifunctional collagen-based nanocomposites. Here, α‑zirconium phosphate nanoplatelets (ZrP NPs) were surface-functionalized with gallic acid (GA) to afford ZrP-GA NPs for engineering CFs matrix. The influence of ZrP-GA NPs on the ultraviolet barrier, antibacterial, and flame-retardant properties of resultant CFs matrix were investigated. Microstructural analysis revealed that ZrP-GA NPs were dispersed and bound within the collagen fibrils and onto the collagen strands in the CFs matrix. The resultant CFs matrix also maintained typical D-periodic structures of collagen fibrils and native branching and interwoven structures of CFs networks with increased porosity and enhanced ultraviolet barrier properties. Inhibition zone testing presented excellent antibacterial activities of the CFs matrix owing to surface grafting of antibacterial GA. Thanks to enhanced dispersion and binding of ZrP NPs with the CFs matrix by surface-functionalization with GA, the resultant CFs matrix reduced the peak heat release rate and the total heat release by 42.9 % and 39.0 %, respectively, highlighting improved flame-retardant properties. We envision that two-dimensional nanomaterials possess great potential in developing reasonable collagen-based nanocomposites towards the manufacture of emergent multifunctional collagen fibers-based wearable electronics.


Conformation of the VP2 protein of bluetongue virus (BTV) determines the involvement in virus neutralization of highly conserved epitopes within the BTV serogroup.
Seven neutralizing monoclonal antibodies (N-MAbs) were generated to an Australian isolate of bluetongue virus serotype 1 [BTV-1 (Aust)]. At least five of the N-MAbs were specific for epitopes on the outer coat protein VP2 and one was capable of binding SDS-treated protein in a Western blot. Six of the N-MAb panel bound and four of these neutralized BTV-1 (South Africa). None of the N-MAbs neutralized other Australian or South African BTV serotypes. However four of the N-MAb panel bound to a majority and two others bound with varying efficiency, to a more restricted but significant number of heterologous serotypes. Thus epitopes involved in the definition of one BTV serotype may be preserved on other serotypes but not be involved in their neutralization. To investigate the association between these epitopes and factors governing their expression, pools of neutralization-escape variants of BTV-1 (Aust), selected using each of six N-MAbs, were tested in virus neutralization and ELISA binding assays against the N-MAb panel. Each N-MAb displayed a unique reaction pattern with all 25 variants tested. All variants except one showed resistance to neutralization and/or reduced binding with at least three heterologous N-MAbs indicating the N-MAb-defined epitopes were mutually interactive. All 25 variants demonstrated increased resistance to neutralization by a bovine antiserum to BTV-1 (Aust). In total, the results from the variants revealed that the N-MAbs define seven distinct, interdependent neutralization epitopes which form at least part of a major neutralization domain on BTV. A majority of variants bound at least four and up to six N-MAbs, yet still resisted neutralization by them. This observation and the reaction of N-MAbs with BTV-1 (South Africa) and heterologous serotypes suggested that the conformation of the VP2 protein determines whether epitopes, conserved within the BTV serogroup, are involved in neutralization of individual serotypes of the virus.


MRI and (1)H MRS evaluation for the serial bile duct changes in hamsters after infection with Opisthorchis viverrini.
A 3T MR scanner was used to investigate the relationship between the alteration of bile duct lesions and the hepatic metabolic changes in hamsters infected with Opisthorchis viverrini by using 3T MRI and (1)H MR spectroscopy. Animals were divided into control and infected groups. Five normal hamsters were used as control; fifty-five hamsters were infected with O. viverrini to induce bile duct lesions and hepatic metabolic changes. T2-weighted image sequence in three orthogonal planes were conducted by MRI scans. Single-voxel (1)H MRS was performed to obtain the relative choline-to-lipid ratios. The livers and bile ducts were excised for the histologic examination. The progression of bile duct changes by histology and metabolic changes in O. viverrini infected hamsters were co-investigated. In the O. viverrini-infected group, the T2-weighted images revealed the time-dependent intra- and extra-hepatic duct dilatations in the liver. The mean (±SD) choline-to-lipid ratios were 0.11±0.035 in the control group, whereas the ratio in the infected group increased significantly with the progression of time. Histologic grading of hepatic inflammation and fibrosis were correlated well with the MRI grading (Spearman rank correlation test; r=0.746 and p<0.001). The control group showed no dilatation of the bile ducts and showed normal liver patterns. Noninvasive technique, MRI and (1)H MRS can demonstrated and applied to evaluate not only the inflammation-related fibrosis in the small bile ducts but also the metabolic changes in the liver induced by O. viverrini infection. A significant increase in the choline-to-lipids ratios were observed in parallel with the time-course of infection. O. viverrini infected in human is detected by stool examination. Hepatobiliary morbidity is detected and followed up by ultrasonography. MRI and MRS can be used in conjunction with ultrasonography for evaluation of progression of the disease.


Nonparametric tensor ring decomposition with scalable amortized inference.
Multi-dimensional data are common in many applications, such as videos and multi-variate time series. While tensor decomposition (TD) provides promising tools for analyzing such data, there still remains several limitations. First, traditional TDs assume multi-linear structures of the latent embeddings, which greatly limits their expressive power. Second, TDs cannot be straightforwardly applied to datasets with massive samples. To address these issues, we propose a nonparametric TD with amortized inference networks. Specifically, we establish a non-linear extension of tensor ring decomposition, using neural networks, to model complex latent structures. To jointly model the cross-sample correlations and physical structures, a matrix Gaussian process (GP) prior is imposed over the core tensors. From learning perspective, we develop a VAE-like amortized inference network to infer the posterior of core tensors corresponding to new tensor data, which enables TDs to be applied to large datasets. Our model can be also viewed as a kind of decomposition of VAE, which can additionally capture hidden tensor structure and enhance the expressiveness power. Finally, we derive an evidence lower bound such that a scalable optimization algorithm is developed. The advantages of our method have been evaluated extensively by data imputation on the Healing MNIST dataset and four multi-variate time series data.


[Magnetic susceptibility of rhodopsin molecules].
It has been calculated that if rhodopsin molecules are associated in photoreceptor membranes they have such a high diamagnetic susceptibility anisotropy that it manifests itself macroscopically in the magnetic field in the order of magnitude of 0.1 kG (8 . 10(3) A/m), but the velocity of this orientation is very low. Thus the interaction with the magnetic field might be limited by kinetics. Malignant transformation is as a rule accompanied by changes in 1) the properties of membrane proteins, 2) their orientation in the membrane, 3) the physical state of lipids in which the membrane proteins are located. Under definite conditions these changes can lead to selective effects of the magnetic fields on the growth of cancer cells in vitro and in vivo (see ref. 2). It is also suggested from thermodynamic considerations that the magnetic anisotropy of biological material (membrane proteins, collagenous structures, muscle and chromatin fibres) might be one of the bases of other biological effects of magnetic fields.


Centriole translocation and degeneration during ciliogenesis in Caenorhabditis elegans neurons.
Neuronal cilia that are formed at the dendritic endings of sensory neurons are essential for sensory perception. However, it remains unclear how the centriole-derived basal body is positioned to form a template for cilium formation. Using fluorescence time-lapse microscopy, we show that the centriole translocates from the cell body to the dendrite tip in the Caenorhabditis elegans sensory neurons. The centriolar protein SAS-5 interacts with the dynein light-chain LC8 and conditional mutations of cytoplasmic dynein-1 block centriole translocation and ciliogenesis. The components of the central tube are essential for the biogenesis of centrioles, which later drive ciliogenesis in the dendrite; however, the centriole loses these components at the late stage of centriole translocation and subsequently recruits transition zone and intraflagellar transport proteins. Together, our results provide a comprehensive model of ciliogenesis in sensory neurons and reveal the importance of the dynein-dependent centriole translocation in this process.


Prenatal caffeine intake differently affects synaptic proteins during fetal brain development.
Caffeine is the psychostimulant most consumed worldwide. However, little is known about its effects during fetal brain development. In this study, adult female Wistar rats received caffeine in drinking water (0.1, 0.3 and 1.0 g/L) during the active cycle in weekdays, two weeks before mating and throughout pregnancy. Cerebral cortex and hippocampus from embryonic stages 18 or 20 (E18 or E20, respectively) were collected for immunodetection of the following synaptic proteins: brain-derived neurotrophic factor (BDNF), TrkB receptor, Sonic Hedgehog (Shh), Growth Associated Protein 43 (GAP-43) and Synaptosomal-associated Protein 25 (SNAP-25). Besides, the estimation of NeuN-stained nuclei (mature neurons) and non-neuronal nuclei was verified in both brain regions and embryonic periods. Caffeine (1.0 g/L) decreased the body weight of embryos at E20. Cortical BDNF at E18 was decreased by caffeine (1.0 g/L), while it increased at E20, with no major effects on TrkB receptors. In the hippocampus, caffeine decreased TrkB receptor only at E18, with no effects on BDNF. Moderate and high doses of caffeine promoted an increase in Shh in both brain regions at E18, and in the hippocampus at E20. Caffeine (0.3g/L) decreased GAP-43 only in the hippocampus at E18. The NeuN-stained nuclei increased in the cortex at E20 by lower dose and in the hippocampus at E18 by moderate dose. Our data revealed that caffeine transitorily affect synaptic proteins during fetal brain development. The increased number of NeuN-stained nuclei by prenatal caffeine suggests a possible acceleration of the telencephalon maturation. Although some modifications in the synaptic proteins were transient, our data suggest that caffeine even in lower doses may alter the fetal brain development.


Veterinarians Experience Animal Welfare Control Work as Stressful.
The aim of the study was to evaluate the job satisfaction of official veterinarians working in the field of animal welfare control and identify both positive features and challenges of their work. An electronic questionnaire was designed to evaluate job satisfaction. The questionnaire was responded to by 73 of the 98 Finnish official veterinarians working in the field of animal welfare control. The Spearman's rank correlation coefficient was used to evaluate the relation between stress and different work-related factors. More than half of the respondents reported work-related stress or fatigue. Threatening situations, disturbed work-private life balance and a high amount of overtime work were found to be frequent underlying causes of stress. Fieldwork, especially when working alone, was perceived as the most challenging part of the work. Of the respondents, three out of four performed animal welfare inspections mainly alone. Although the respondents reported getting additional help to perform an inspection most of the times they needed it, a wish to work in a pair was highlighted. The results of the present study indicate that official veterinarians often experience work-related stress and fatigue. By testing interventions shown to be beneficial, such as providing adequate support within the work community, decreasing the workload and enabling inspections to be done in pairs, job satisfaction could be improved.


Oxidation of thiosulfate by a new bacterium, Bosea thiooxidans (strain BI-42) gen. nov., sp. nov.: analysis of phylogeny based on chemotaxonomy and 16S ribosomal DNA sequencing.
A gram-negative bacterium which was capable of oxidizing reduced inorganic sulfur compounds was isolated from agricultural soil and designated BI-42. This new isolate grew on a wide range of organic substrates but was not able to grow autotrophically and lacked ribulose 1,5-bisphosphate carboxylase, a key enzyme of carbon dioxide fixation. These results suggested that strain BI-42 was a chemolithoheterotroph. Ammonia and nitrate were not used as sole nitrogen sources for growth, and strain BI-42 lacked glutamate synthase activity, which resulted in glutamate auxotrophy. The glutamate dehydrogenase activity of this organism was apparently insufficient for ammonia assimilation. On the basis of the results of additional biochemical tests, the G + C content of the DNA, the results of a respiratory ubiquinone analysis, the results of a 16S ribosomal DNA sequence analysis, the fatty acid composition, and the results of a membrane lipid analysis, strain BI-42 was identified as a phylogenetically and physiologically distinct taxon belonging to the alpha subclass of the Proteobacteria. Bosea thiooxidans gen. nov., sp. nov. is the name proposed for this taxon.


[Pathophysiological basis of 3 subtypes in ganfeng neidong syndrome].
The multiple parameters of 3 Subtypes: Ganyang Huafeng Syndrome (GYHFS), Xuexu Shengfeng Syndrome and Yinxu Fengdong Syndrome of Ganfeng Neidong Syndrome were determined for the 1st time. It was found that there were several characteristics in GYHFS. (1) Disturbance of the cerebral blood flow and the damage of brain tissue was manifested by the abnormality of the bulbar conjunctival microcirculation, carotid Doppler ultrasonic determination and brainstem auditory and visual pathway, high blood viscosity, dysmnesia, free radical and lipid peroxidation injury and the changes of Zn, Cu, K and Mg after brain damage. (2) Stress status were expressed by the high plasma levels of cortisol, norepinephrine and epinephrine, decreased serum triiodothyronine level and hyperfunction of sympathetic nerve. (3) The marked changes of the regulating substance of the vessel smooth muscle function including the increased plasma levels of TXB2, TXB2/6-k-PGF1 alpha, and calmodulin, as well as decreased SP, ANP, CGRP. Other 2 subtypes had about the same changes of these parameters, but of milder disorders.


X-ray collimation by crystals with precise parabolic holes based on diffractive-refractive optics.
Two crystals with precise parabolic holes were used to demonstrate sagittal beam collimation by means of a diffractive-refractive double-crystal monochromator. A new approach is introduced and beam collimation is demonstrated. Two Si(333) crystals with an asymmetry angle of α = 15° were prepared and arranged in a dispersive position (+,-,-,+). Based on theoretical calculations, this double-crystal set-up should provide tunable beam collimation within an energy range of 6.3-18.8 keV (Θ(B) = 71-18.4°). An experiment study was performed on BM05 at ESRF. Using 8.97 keV energy, the beam profile at various distances was measured. The experimental results are in good agreement with theoretical predictions. Owing to insufficient harmonic suppression, the collimated (333) beam was overlapped by horizontally diverging (444) and (555) beams.


High-resolution functional mapping of a cloned gene by genetic footprinting.
We describe an efficient method for introducing and analyzing a comprehensive set of mutations in a cloned gene to map its functional organization. The technique, genetic footprinting, uses a retroviral integrase to generate a comprehensive library of mutants, each of which bears a single insertion of a defined oligonucleotide at a random position in the gene of interest. This mutant library is selected for gene function en masse. DNA samples are isolated from the library both before and after selection, and the mutations represented in each sample are then analyzed. The analysis is designed so that a mutation at a particular location gives rise to an electrophoretic band of discrete mobility. For the whole library, this results in a ladder of bands, each band representing a specific mutation. Mutants in which the inserted sequence disrupts a feature that is required for the selected function, ipso facto, fail the selection. The corresponding bands are therefore absent from the ladder of bands obtained from the library after selection, giving rise to a footprint representing features of the gene that are essential for the selected function. Because the sequence of the inserted oligonucleotide is known, and its position can be inferred precisely from the electrophoretic mobility of the corresponding band, the precise location and sequence of mutations that disrupt gene function can be determined without isolating or sequencing individual mutants. This method should be generally applicable for saturation mutagenesis and high-resolution functional mapping of cloned DNA sequences.


Biosystematics of alkaliphilic streptomycetes isolated from seven locations across a beach and dune sand system.
Alkaliphilic streptomycetes were isolated from composite sand samples collected from six out of seven locations across a beach and dune sand system using starch-casein-nitrate agar supplemented with cycloheximide and buffered to pH 10.5. The isolates had colonial and chemotaxonomic properties consistent with their classification in the genus Streptomyces. They were assigned to 49 multimembered and 114 single-membered colour-groups given their ability to produce pigments on oatmeal and peptone-yeast-extract-iron agars and to corresponding taxa based on whole-genome rep-PCR banding patterns. Twenty-four isolates representing the colour and rep-PCR groups grew well from pH 5 to 11, and optimally at pH 9, as did phylogenetically close members of the Streptomyces griseus 16S rRNA gene clade. One hundred and twelve representative alkaliphilic streptomycetes formed a heterogeneous but distinct clade in the Streptomyces 16S rRNA gene tree. A 3-dimensional representation of 16S rRNA sequence data showed that the alkaliphilic streptomycetes formed a distinct group in multidimensional taxospace. It is evident that alkaliphilic streptomycetes are common in the beach and dune sand system and that representatives of this community form new centers of taxonomic variation within the genus Streptomyces that can be equated with species.


[Structural basis of developmental changes in the cytoarchitecture of human neocortex transplants].
Early stages in development of transplants of the embryonal anlages of the human neocortex into the brain of mature rats have been studied at light optic level. The main attention has been paid to processes of proliferation, migration and differentiation of cells. Increasing amount of cells in the transplants takes place only at the expense of neuroepithelium; its reorganization results in a peculiar rearrangement of cells with formation of so called rosellas with numerous mitotically dividing cells. Owing to this growth the differentiating cells migrate from the rosellas radially, unlike their layer-by-layer organization in the control. These deviations are probably dominant in the disturbance of cytoarchitectonic organization of cells in transplants of neocortex in mature mammalia.


Modeling Virus Coinfection to Inform Management of Maize Lethal Necrosis in Kenya.
Maize lethal necrosis (MLN) has emerged as a serious threat to food security in sub-Saharan Africa. MLN is caused by coinfection with two viruses, Maize chlorotic mottle virus and a potyvirus, often Sugarcane mosaic virus. To better understand the dynamics of MLN and to provide insight into disease management, we modeled the spread of the viruses causing MLN within and between growing seasons. The model allows for transmission via vectors, soil, and seed, as well as exogenous sources of infection. Following model parameterization, we predict how management affects disease prevalence and crop performance over multiple seasons. Resource-rich farmers with large holdings can achieve good control by combining clean seed and insect control. However, crop rotation is often required to effect full control. Resource-poor farmers with smaller holdings must rely on rotation and roguing, and achieve more limited control. For both types of farmer, unless management is synchronized over large areas, exogenous sources of infection can thwart control. As well as providing practical guidance, our modeling framework is potentially informative for other cropping systems in which coinfection has devastating effects. Our work also emphasizes how mathematical modeling can inform management of an emerging disease even when epidemiological information remains scanty. [Formula: see text] Copyright © 2017 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .


Detecting Receptivity for mHealth Interventions in the Natural Environment.
Just-In-Time Adaptive Intervention (JITAI) is an emerging technique with great potential to support health behavior by providing the right type and amount of support at the right time. A crucial aspect of JITAIs is properly timing the delivery of interventions, to ensure that a user is receptive and ready to process and use the support provided. Some prior works have explored the association of context and some user-specific traits on receptivity, and have built post-study machine-learning models to detect receptivity. For effective intervention delivery, however, a JITAI system needs to make in-the-moment decisions about a user's receptivity. To this end, we conducted a study in which we deployed machine-learning models to detect receptivity in the natural environment, i.e., in free-living conditions. We leveraged prior work regarding receptivity to JITAIs and deployed a chatbot-based digital coach - Ally - that provided physical-activity interventions and motivated participants to achieve their step goals. We extended the original Ally app to include two types of machine-learning model that used contextual information about a person to predict when a person is receptive: a static model that was built before the study started and remained constant for all participants and an adaptive model that continuously learned the receptivity of individual participants and updated itself as the study progressed. For comparison, we included a control model that sent intervention messages at random times. The app randomly selected a delivery model for each intervention message. We observed that the machine-learning models led up to a 40% improvement in receptivity as compared to the control model. Further, we evaluated the temporal dynamics of the different models and observed that receptivity to messages from the adaptive model increased over the course of the study.


Small-Volume Adenosine, Lidocaine, and Mg2+ 4-Hour Infusion Leads to 88% Survival after 6 Days of Experimental Sepsis in the Rat without Antibiotics.
Innovative host-directed drug therapies are urgently required to treat sepsis. We tested the effect of a small-volume 0.9% NaCl adenosine, lidocaine, and Mg2+ (ALM) bolus and a 4-h intravenous infusion on survivability in the rat model of polymicrobial sepsis over 6 days. ALM treatment led to a significant increase in survivability (88%) compared to that of controls (25%). Four controls died on day 2 to 3, and two died on day 5. Early death was associated with elevated plasma and lung inflammatory markers (interleukin-6 [IL-6], IL-1β, C-reactive protein), reduced white blood cell (WBC) count, hypoxemia, hypercapnia, acidosis, hyperkalemia, and elevated lactate, whereas late death was associated with a massive cytokine storm, a neutrophil-dominated WBC rebound/overshoot, increased lung oxidant injury, edema, and persistent ischemia. On day 6, seven of eight ALM survivors had inflammatory and immunological profiles not significantly different from those of sham-treated animals. We conclude in the rat model of experimental sepsis that small-volume ALM treatment led to higher survivability at 6 days (88%) than that of controls (25%). Early death in controls (day 2 to 3) was associated with significantly elevated plasma levels of IL-1β, IL-6, and C-reactive protein, severe plasma lymphocyte deficiency, reduced neutrophils, and acute lung injury. Late death (day 5) was associated with a massive neutrophil inflammatory storm, increased lung injury, and persistent ischemia. Possible mechanisms of ALM protection are discussed.


A feasibility study to determine the use of baited pots in Greenland halibut (Reinhardtius hippoglossoides) fisheries, supported by the use of underwater video observations.
High incidental catches of Greenland shark (Somniosus microcephalus) in Nunavut's Greenland halibut (Reinhardtius hippoglossoides) fishery has led to studies on the feasibility of capturing Greenland halibut with baited pots. In this study, catch rates among six experimental pots are compared. In addition to this, underwater video observations of Greenland halibut interacting with two of these experimental pot types are quantified in order to help provide recommendations on future pot designs. Catch rates of Greenland halibut differed among pots with different entrance mesh types, and none of the pots produced substantial amounts of bycatch. Strings of pots were deployed within a narrow corridor between baited gillnets targeting Greenland halibut, which may have affected catch results. Video observations revealed Greenland halibut entangled by their teeth significantly more often in entrance funnels constructed with 50 mm than with 19 mm clear monofilament netting and the entrance rate was 45% higher with the 19 mm netting. Greenland halibut that successfully entered a pot repeatedly became entangled by their teeth in 58 mm netting used in the side and end panels and in a horizontal panel used to separate the pot into a lower and upper chamber. The majority (80%) of Greenland halibut were observed to approach a pot against the current. The downstream entrance was aligned with the current in 52% of the observed Greenland halibut approaches. Seventy percent of entry attempts and 67% of successful entries occurred when fish approached against the current and when the entrance was aligned with the current. These observations lead to recommendations that future studies consider developing a four entrance pot to ensure an entrance is always aligned with bottom currents. Based on these observations of entanglements, it is recommended to use 19 mm clear monofilament netting in the entrance funnel, 100 mm polyethylene netting in the exterior panels, and 19 mm polypropylene netting in the horizontal panel when targeting Greenland halibut. Three Greenland sharks were observed interacting with the pots in the video sets, but none were captured or damaged the pots during the potting experiments, providing validity to the use of pots to mitigate the capture of Greenland shark in Nunavut territorial waters.


Apathy and anhedonia rating scales in Parkinson's disease: critique and recommendations.
Apathy is a common condition in Parkinson's disease (PD) and is generally defined as a lack of motivation. It is associated with more severe cognitive dysfunction and a decrease in activities of daily living (ADL) performance. Anhedonia, the inability to experience pleasure, can be a symptom of both depressive and apathetic syndromes. The Movement Disorder Society (MDS) commissioned a task force to assess the clinimetric properties of apathy and anhedonia scales in PD patients. A systematic literature review was conducted to identify scales that have either been validated or used in PD patients. Apathy scales identified for review include the Apathy Evaluation Scale (AES), the Apathy Scale (AS), the Apathy Inventory (AI), and the Lille Apathy Rating Scale (LARS). In addition, item 4 (motivation/initiative) of the Unified Parkinson's Disease Rating Scale (UPDRS) and item 7 (apathy) of the Neuropsychiatric Inventory (NPI) were included. Anhedonia scales identified for review were the Snaith-Hamilton Pleasure Scale (SHAPS) and the Chapman scales for physical and social anhedonia. Only the AS is classified as "recommended" to assess apathy in PD. Although item 4 of the UPDRS also meets the criteria to be classified as recommended, it should be considered for screening only because of the obvious limitations of a single item construct. For the assessment of anhedonia, only the SHAPS meets the criteria of "Suggested." Information on the validity of apathy and anhedonia scales is limited because of the lack of consensus on diagnostic criteria for these conditions.


Improvements in lung compliance after pulmonary transplantation: correlation with interleukin 8 expression.
Previous studies have suggested reductions in lung reperfusion injury when initial reperfusion is undertaken with the addition of pharmacological modulators. We investigated three pharmacological agents in a porcine model of left single lung transplantation to determine the effect on lung compliance and its relationship with the expression of the cytokine, interleukin-8 (IL-8). Donor lungs were preserved with modified Euro-Collins for a mean ischaemic time of 18.6 h. Pulmonary venous oxygenation, lung compliance and IL-8 expression were assessed over a 12-h period. Group A (n=5) was a control group with no interventions added, Group B was reperfused with the addition of intravenous inositol hexakisphosphate (InSP6) (0.02 mg/kg per min), Group C received the nitric oxide donor, 3-morpholinosydnonimine (SIN-1) (0.02 mg/kg per min) and Group D received intravenous Pentoxifylline (2 mg/kg per h). All interventions were administered at a pulmonary artery pressure of 20 mmHg. Group D yielded the best oxygenation (P=0.0041) while Groups B and C were similar. All were superior to Group A (P<0.001). Lung compliance was significantly improved in Groups B, C and D compared to group A. In Group D, the greatest improvements in lung compliance were observed (P<0.0001). Similar observations were seen with regard to pulmonary vascular resistance. IL-8 expression was delayed until after 30 min of reperfusion in Group D, but was evident after 10 min in all the other groups. This correlates with the compliance and oxygenation data. The addition of InSP6 or SIN-1 at reperfusion significantly attenuates reperfusion injury compared with controls and improves lung compliance. The unique comparison with Pentoxifylline afforded by this study indicates that at the doses studied Pentoxifylline appears to be superior, correlating with a greater inhibition of IL-8 expression.


Reliability of an audit tool for systematic assessment of urban alleyways.
Reliable audit tools are needed to examine the potential of built environment features for physical activity. An audit tool for alley environments was developed with land use, substrate, and use, condition, and safety items. Two audit teams independently audited 29 Los Angeles alleys, and interteam reliability was calculated with Cohen's and prevalence-adjusted, bias-adjusted kappa (PABAK) statistics; intraclass correlation coefficients; and percent observed agreement. Forty-two of 47 dichotomous items analyzed for reliability had PABAK values > or = 0.61 ("substantial agreement"). Sixteen of 23 ordinal and continuous response items analyzed had ICCs > or = 0.61, and an additional 6 with lower ICC values had observed agreement > or = 79%. Items concerning the presence or absence of use-related alley features demonstrated the lowest reliability. The instrument has acceptable reliability for most of its items and appears to be a promising tool for use by other researchers and professionals in the measurement of alley environments.


Identification and characterization of an anterior fat body protein in an insect.
We purified a novel protein with a molecular mass of 34 kDa from the Sarcophaga larval fat body. This protein, named AFP (anterior fat body protein), was restricted almost exclusively to the anterior fat body. The AFP content decreased after pupation on disintegration of the fat body tissue. cDNA analysis revealed that this protein consists of 306 amino acid residues and exhibits significant structural similarity with mammalian regucalcin (senescence marker protein-30), a calcium-binding liver protein. However, AFP did not seem to exhibit strong affinity with calcium. These results suggested that a seemingly uniform fat body tissue exhibits a regional difference in its function along the anterior-posterior axis.


ECPIRM, a Potential Therapeutic Agent for Cutaneous T-Cell Lymphoma, Inhibits Cell Proliferation and Promotes Apoptosis via a JAK/STAT Pathway.
Retinoids are important agents for the treatment of cutaneous T-cell lymphomas (CTCL). But side effects and drug resistance caused by activation of RAR/RXR limited their clinical application. Therefore, it is urgent to develop new agents to fight against CTCL. ECPIRM, a 13-cis retinoic acid derivative, was reported that it inhibited proliferation and induced apoptosis of SCL-1 cells. The aim of this study was to evaluate the biological activities and mechanisms of ECPIEM. The effect of ECPIRM on cell proliferation was determined by MTT assay and Trypan blue exclusion assay while FACS analysis was used to detect changes in cell cycle and apoptosis in HUT78 cells. The influence of ECPIRM on RAR/RXR and JAK/STAT signaling was evaluated by western blot analysis. ECPIRM, better than other agents (all-trans retinoic acid,13-cis-retinoic acid or bexarotene), inhibited proliferation and induced apoptosis significantly in HUT78 cells, but with little cytotoxicity on normal lymphocytes. Then ECPIRM induced G0/G1 phase arrest by decreasing the expression of cyclinD1, cyclinE, CDK2 and CDK4 while increasing p21. Furthermore, the unaffected expression of RAR and RXR members suggested that ECPIRM acted independently of RAR/RXR pathway in HUT78 cells. But decreased phosphorylation of JAK1, STAT3, STAT5 and downregulated Bcl-xL, Cyclin D1 and c-Myc indicated that ECPIRM inhibited the activation of JAK/STAT signaling. ECPIRM inhibited proliferation, induced apoptosis and G0/G1 phase arrest in HUT78 cells through inhibiting JAK/STAT pathway but not RAR/RXR pathway, which presented ECPIRM as a promising candidate for the treatment of CTCL patients.


Helicobacter pylori infection and chronic immune thrombocytopenic purpura: long-term results of bacterium eradication and association with bacterium virulence profiles.
Eradication of Helicobacter pylori may lead to improvement of chronic immune thrombocytopenic purpura (ITP), although its efficacy over time is uncertain. We report the results of H pylori screening and eradication in 75 consecutive adult patients with ITP. We also used molecular methods to investigate lymphocyte clonality and H pylori genotypes in the gastric biopsies from 10 H pylori-positive patients with ITP and 19 H pylori-positive patients without ITP with chronic gastritis. Active H pylori infection was documented in 38 (51%) patients and successfully eradicated in 34 (89%) patients. After a median follow-up of 60 months, a persistent platelet response in 23 (68%) of patients with eradicated infection was observed; 1 relapse occurred. No differences in mucosal B- or T-cell clonalities were observed between patients with ITP and control participants. Of note, the frequency of the H pylori cagA gene (P = .02) and the frequency of concomitant H pylori cagA, vacAs1, and iceA genes (triple-positive strains; P = .015) resulted statistically higher in patients with ITP than in control participants. All asymptomatic H pylori-positive patients with ITP were suffering from chronic gastritis. Our data suggest a sustained platelet recovery in a proportion of patients with ITP by H pylori eradication alone. Overrepresentation of specific H pylori genotypes in ITP suggests a possible role for bacterium-related factors in the disease pathogenesis.


A statistical method (cross-validation) for bone loss region detection after spaceflight.
Astronauts experience bone loss after the long spaceflight missions. Identifying specific regions that undergo the greatest losses (e.g. the proximal femur) could reveal information about the processes of bone loss in disuse and disease. Methods for detecting such regions, however, remains an open problem. This paper focuses on statistical methods to detect such regions. We perform statistical parametric mapping to get t-maps of changes in images, and propose a new cross-validation method to select an optimum suprathreshold for forming clusters of pixels. Once these candidate clusters are formed, we use permutation testing of longitudinal labels to derive significant changes.