Hospital financing of ischaemic stroke: determinants of funding and usefulness of DRG subcategories based on severity of illness.
Several Western and Arab countries, as well as over 30 States in the US are using the "All-Patient Refined Diagnosis-Related Groups" (APR-DRGs) with four severity-of-illness (SOI) subcategories as a model for hospital funding. The aim of this study is to verify whether this is an adequate model for funding stroke hospital admissions, and to explore which risk factors and complications may influence the amount of funding. A bottom-up analysis of 2496 ischaemic stroke admissions in Belgium compares detailed in-hospital resource use (including length of stay, imaging, lab tests, visits and drugs) per SOI category and calculates total hospitalisation costs. A second analysis examines the relationship between the type and location of the index stroke, medical risk factors, patient characteristics, comorbidities and in-hospital complications on the one hand, and the funding level received by the hospital on the other hand. This dataset included 2513 hospitalisations reporting on 35,195 secondary diagnosis codes, all medically coded with the International Classification of Disease (ICD-9). Total costs per admission increased by SOI (€3710-€16,735), with severe patients costing proportionally more in bed days (86%), and milder patients costing more in medical imaging (24%). In all resource categories (bed days, medications, visits and imaging and laboratory tests), the absolute utilisation rate was higher among severe patients, but also showed more variability. SOI 1-2 was associated with vague, non-specific stroke-related ICD-9 codes as primary diagnosis (71-81% of hospitalisations). 24% hospitalisations had, in addition to the primary diagnosis, other stroke-related codes as secondary diagnoses. Presence of lung infections, intracranial bleeding, severe kidney disease, and do-not-resuscitate status were each associated with extreme SOI (p < 0.0001). APR-DRG with SOI subclassification is a useful funding model as it clusters stroke patients in homogenous groups in terms of resource use. The data on medical care utilisation can be used with unit costs from other countries with similar healthcare set-ups to 1) assess stroke-related hospital funding versus actual costs; 2) inform economic models on stroke prevention and treatment. The data on diagnosis codes can be used to 3) understand which factors influence hospital funding; 4) raise awareness about medical coding practices.


Controlled Release of Pyrimidine Compound Using Polymeric Coated ZIF-8 Metal-Organic Framework as Glucagon-Like Peptide-1 Receptor Agonist Carrier.
This work demonstrates synthetic strategies for the incorporation of a synthesized pyrimidine glucagon-like peptide-1 (GLP-1) agonist into alginate-coated ZIF-8. The prepared pyrimidine GLP-1 agonist used for the treatment of diabetes type II, was trapped inside polymer coated ZIF-8. The encapsulation of the GLP-1 agonist was confirmed by UV-visible and FT-IR spectroscopies. Furthermore, the release kinetics of GLP-1 agonist drug from alginate-coated ZIF-8 were investigated in phosphate-buffered saline at 37 °C at pH 8 and 1.5. The alginate-coated ZIF-8 exhibited much faster drug release at basic pH than at pH 1.5, indicating the potential of the alginate-coated ZIF-8 system to overcome the fast degradation at acidic pH of the stomach and improve the drug's activity. This study may open the way for the synthesis of new metal organic frameworks (MOFs) to enhance drug delivery systems.


Modeling COVID-19 and Its Impacts on U.S. Immigration and Customs Enforcement (ICE) Detention Facilities, 2020.
U.S. Immigration and Customs Enforcement (ICE) facilities house thousands of undocumented immigrants in environments discordant with the public health recommendations to reduce the transmission of 2019 novel coronavirus (COVID-19). Using ICE detainee population data obtained from the ICE Enforcement and Removal Operations (ERO) website as of March 2, 2020, we implemented a simple stochastic susceptible-exposed-infected-recovered model to estimate the rate of COVID-19 transmission within 111 ICE detention facilities and then examined impacts on regional hospital intensive care unit (ICU) capacity. Models considered three scenarios of transmission (optimistic, moderate, pessimistic) over 30-, 60-, and 90-day time horizons across a range of facility sizes. We found that 72% of individuals are expected to be infected by day 90 under the optimistic scenario (R0 = 2.5), while nearly 100% of individuals are expected to be infected by day 90 under a more pessimistic (R0 = 7) scenario. Although asynchronous outbreaks are more likely, day 90 estimates provide an approximation of total positive cases after all ICE facility outbreaks. We determined that, in the most optimistic scenario, coronavirus outbreaks among a minimum of 65 ICE facilities (59%) would overwhelm ICU beds within a 10-mile radius and outbreaks among a minimum of 8 ICE facilities (7%) would overwhelm local ICU beds within a 50-mile radius over a 90-day period, provided every ICU bed was made available for sick detainees. As policymakers seek to rapidly implement interventions that ensure the continued availability of life-saving medical resources across the USA, they may be overlooking the pressing need to slow the spread of COVID-19 infection in ICE's detention facilities. Preventing the rapid spread necessitates intervention measures such as granting ICE detainees widespread release from an unsafe environment by returning them to the community.


Denial of abortion in legal settings.
Factors such as poverty, stigma, lack of knowledge about the legal status of abortion, and geographical distance from a provider may prevent women from accessing safe abortion services, even where abortion is legal. Data on the consequences of abortion denial outside of the US, however, are scarce. In this article we present data from studies among women seeking legal abortion services in four countries (Colombia, Nepal, South Africa and Tunisia) to assess sociodemographic characteristics of legal abortion seekers, as well as the frequency and reasons that women are denied abortion care. The proportion of women denied abortion services and the reasons for which they were denied varied widely by country. In Colombia, 2% of women surveyed did not receive the abortions they were seeking; in South Africa, 45% of women did not receive abortions on the day they were seeking abortion services. In both Tunisia and Nepal, 26% of women were denied their wanted abortions. The denial of legal abortion services may have serious consequences for women's health and wellbeing. Additional evidence on the risk factors for presenting later in pregnancy, predictors of seeking unsafe illegal abortion, and the health consequences of illegal abortion and childbirth after an unwanted pregnancy is needed. Such data would assist the development of programmes and policies aimed at increasing access to and utilisation of safe abortion services where abortion is legal, and harm reduction models for women who are unable to access legal abortion services.


Therapeutic interventions of remdesivir in diabetic and nondiabetic COVID-19 patients: A prospective observational study conducted on Pakistani population.
We aimed to investigate the interventions of remdesivir in both diabetic and nondiabetic individuals who were suffering from a severe infection of novel coronavirus disease (COVID-19). In this study, we aimed to explore the relationship between therapeutic effectiveness of remdesivir and complications of diabetes mellitus by observing the recovery period among diabetic and nondiabetic patients associated with COVID-19 infection. A total of 850 COVID-19 patients were recruited for this study, out of which 48% were diabetic and 52% were nondiabetics. The results of this study indicated that nondiabetic individuals administered with remdesivir recovered from COVID-19 within 10 days showing a 95% confidence interval (p < 0.01), while the diabetic individuals recovered in 15 days. Nondiabetic patients administered with remdesivir exhibited higher chances of clinical improvement at 15th day than those who were associated with diabetes. Remdesivir administration improved the levels of various biochemical parameters, such as C-reactive protein, lactate dehydrogenase, d-Dimer, and ferritin both in diabetic and nondiabetic patients. However, a significant improvement (p < 0.01) was seen in the level of biochemical parameters among nondiabetic patients as compared to that of diabetic patients administered with remdesivir treatment. In the end, it was concluded that remdesivir could be considered as a possible therapeutic agent in the treatment of COVID-19 both in diabetic and nondiabetic situations. However, diabetic patients showed a delayed recovery as compared with that of nondiabetic patients, in which the recovery rate was high.


Expression of the glioma-associated oncogene homolog (GLI) 1 in human breast cancer is associated with unfavourable overall survival.
The transcription factor GLI1, a member of the GLI subfamily of Krüppel-like zinc finger proteins is involved in signal transduction within the hedgehog pathway. Aberrant hedgehog signalling has been implicated in the development of different human tumour entities such as colon and lung cancer and increased GLI1 expression has been found in these tumour entities as well. In this study we questioned whether GLI1 expression might also be important in human breast cancer development. Furthermore we correlated GLI1 expression with histopathological and clinical data to evaluate whether GLI1 could represent a new prognostic marker in breast cancer treatment. Applying semiquantitative realtime PCR analysis and immunohistochemistry (IHC) GLI1 expression was analysed in human invasive breast carcinomas (n = 229) in comparison to normal human breast tissues (n = 58). GLI1 mRNA expression was furthermore analysed in a set of normal (n = 3) and tumourous breast cell lines (n = 8). IHC data were statistically interpreted using SPSS version 14.0. Initial analysis of GLI1 mRNA expression in a small cohort of (n = 5) human matched normal and tumourous breast tissues showed first tendency towards GLI1 overexpression in human breast cancers. However only a small sample number was included into these analyses and values for GLI1 overexpression were statistically not significant (P = 0.251, two-tailed Mann-Whitney U-test). On protein level, nuclear GLI1 expression in breast cancer cells was clearly more abundant than in normal breast epithelial cells (P = 0.008, two-tailed Mann-Whitney U-test) and increased expression of GLI1 protein in breast tumours significantly correlated with unfavourable overall survival (P = 0.019), but also with higher tumour stage (P < 0.001) and an increased number of tumour-positive axillar lymph nodes (P = 0.027). Interestingly, a highly significant correlation was found between GLI1 expression and the expression of SHH, a central upstream molecule of the hedgehog pathway that was previously analysed on the same tissue microarray. Our study presents a systematic expression analysis of GLI1 in human breast cancer. Elevated levels of GLI1 protein in human breast cancer are associated with unfavourable prognosis and progressive stages of disease. Thus GLI1 protein expression measured e.g. by an IHC based scoring system might have an implication in future multi-marker panels for human breast cancer prognosis or molecular sub typing. The highly significant correlation between SHH and GLI1 expression characterises GLI1 as a potential functional downstream target of the hedgehog signalling pathway in human breast cancer as well. Furthermore, our study indicates that altered hedgehog signalling may represent a key disease pathway in the progression of human breast cancer.


Eribulin mesylate for the treatment of patients with refractory metastatic breast cancer: use of a "physician's choice" control arm in a randomized approval trial.
This work describes the considerations that led to the approval by the U.S. Food and Drug Administration (FDA), on November 15, 2010, of eribulin mesylate (Halaven; Eisai, Inc.) for the treatment of patients with refractory metastatic breast cancer. The FDA review focused primarily on the results of a single randomized, open-label, multicenter trial of 762 patients with refractory locally advanced or metastatic breast cancer. The patients were randomized to receive eribulin or any single-agent treatment of the physician's choice, selected prior to randomization. The FDA's approval of eribulin mesylate was based on demonstration of a statistically significant prolongation of overall survival (OS) in patients who had been randomized to receive eribulin. The median OS was 13.1 months in the eribulin arm compared with 10.6 months in the control arm [HR 0.81 (95% CI, 0.66-0.99); P = 0.041]. Treatment with eribulin did not show a statistically significant treatment effect [HR 0.87 (95% CI, 0.71-1.05)] on progression-free survival as determined by independent review. This approval highlights the appropriate use of an innovative trial design and shows that improvement in OS is an achievable endpoint in the setting of advanced breast cancer. On the basis of the different conclusions arising from the OS and progression-free survival results, investigators should consider using OS as a primary endpoint in clinical trials for refractory breast cancer.


Scoring systems for the Clock Drawing Test: A historical review.
The Clock Drawing Test (CDT) is a simple neuropsychological screening instrument that is well accepted by patients and has solid psychometric properties. Several different CDT scoring methods have been developed, but no consensus has been reached regarding which scoring method is the most accurate. This article reviews the literature on these scoring systems and the changes they have undergone over the years. Historically, different types of scoring systems emerged. Initially, the focus was on screening for dementia, and the methods were both quantitative and semi-quantitative. Later, the need for an early diagnosis called for a scoring system that can detect subtle errors, especially those related to executive function. Therefore, qualitative analyses began to be used for both differential and early diagnoses of dementia. A widely used qualitative method was proposed by Rouleau et al. (1992). Tracing the historical path of these scoring methods is important for developing additional scoring systems and furthering dementia prevention research.


Amphetamine, but not reserpine, protects mice against dopaminergic neurotoxicity of MPTP.
In mice, long-term reductions in striatal DA produced by the neurotoxin MPTP were completely prevented by its combined administration with amphetamine. Depletion of DA from DA terminals by cotreatment with reserpine did not suppress but rather enhanced MPTP-induced DA decrements in striatum. Amphetamine protection against DA neurotoxicity of MPTP in mice is probably not due to increases in DA release and may be related to inhibition of MPTP transport into nigrostriatal terminals via the DA reuptake system.


Norton scale scores and 1-year mortality in elderly patients following lower limb amputations.
The Norton scale is used for assessing the risk of pressure ulcers. The association between low admission Norton scale scores (ANSS), complications and mortality in elderly patients following lower limb amputations has never been studied until now. The aim of this study was to investigate if low ANSSs are associated with complications the 30-day and 1-year mortality in elderly patients following lower limb amputations. The medical charts of 104 elderly (≥ 65 years) patients following lower limb amputations were studied for the following measurements: ANSS, demographics, comorbidities, complications during hospitalization, 30-day mortality and 1-year mortality. Complications included acute coronary syndrome, major bleeding, stroke, systemic infections, organ failure and thromboembolism. An ANSS ≤ 14 was considered as being low. Overall 54 (51.9%) patients underwent below-knee amputations and 50 (48.1%) patients underwent above-knee amputations. Most (n = 78; 75.0 %) patients were men and the mean age was 78.5 ± 7.9 years. Following the amputation 46 (44.2%) patients had complications other than pressure ulcers, 24 (23.1%) patients died within 30 days and 63 (60.6%) patients died within 1 year. A total of 61 (58.7%) patients had a low ANSS. The incidence of complications other than pressure ulcers, 30-day and 1-year mortality rates were higher in patients with a low ANSS relative to patients with a high ANSS. A regression analysis showed that 1-year mortality was independently negatively associated with ANSS (t = 2.629; p = 0.010). The Norton scale can be used for predicting 1-year mortality in elderly patients following lower limb amputations.


Genome-Wide Identification and Transcriptome-Based Expression Profile of Cuticular Protein Genes in Antheraea pernyi.
Antheraea pernyi is one of the most famous edible and silk-producing wild silkworms of Saturniidae. Structural cuticular proteins (CPs) are the primary component of insect cuticle. In this paper, the CPs in the genome of A. pernyi were identified and compared with those of the lepidopteran model species Bombyx mori, and expression patterns were analyzed based on the transcriptomic data from the larval epidermis/integument (epidermis in the following) and some non-epidermis tissues/organs of two silkworm species. A total of 217 CPs was identified in the A. pernyi genome, a comparable number to B. mori (236 CPs), with CPLCP and CPG families being the main contribution to the number difference between two silkworm species. We found more RR-2 genes expressed in the larval epidermis of fifth instar of A. pernyi than B. mori, but less RR-2 genes expressed in the prothoracic gland of A. pernyi than B. mori, which suggests that the hardness difference in the larval epidermis and prothoracic gland between the two species may be caused by the number of RR-2 genes expressed. We also revealed that, in B. mori, the number of CP genes expressed in the corpus allatum and prothoracic gland of fifth instar was higher than that in the larval epidermis. Our work provided an overall framework for functional research into the CP genes of Saturniidae.


Genetic variation responsible for mouse strain differences in integrin alpha 2 expression is associated with altered platelet responses to collagen.
As mouse models have become commonplace for studying hemostasis and thrombosis, we considered whether the mouse system had utility for assessing genetic alterations in platelet receptors. Platelets from 5 mouse strains (C57BL/6 [C57], FVB/N [FVB], BALB/c, C3H/He, and 129Sv) showed only minor differences in the expression of integrin alpha(IIb), integrin beta(3), glycoprotein (GP) Ib alpha, or GPVI across strains. However, FVB platelets expressed approximately 50% the level of integrin alpha(2) as platelets from other strains (P <.0001). We bred FVB mice with C57 and assessed alpha(2) expression in FVB/C57xFVB/C57 (F2) offspring. Linkage analysis demonstrated the gene responsible for alpha(2) levels is tightly linked to the D13mit260 marker (log odds [lod] score 6.7) near the alpha(2) gene. FVB platelets showed reduced aggregation and a longer lag phase to collagen. FVB and C57 platelets aggregated similarly to collagen-related peptide, but FVB platelets showed a reduction in rhodocytin-induced Syk and PLC gamma 2 tyrosine phosphorylation. Thus, FVB platelets express half the level of alpha(2) as other mouse strains, a trait linked to the alpha(2) gene and seemingly responsible for reduced platelet aggregation to collagen. These strain differences serve as a useful model for the 2-fold difference in human platelet alpha(2)beta(1) expression and demonstrate that alpha(2)beta(1) participates in signaling during platelet activation.


Focused Ultrasound in Neuroscience. State of the Art and Future Perspectives.
Transcranial MR-guided Focused ultrasound (tcMRgFUS) is a surgical procedure that adopts focused ultrasounds beam towards a specific therapeutic target through the intact skull. The convergence of focused ultrasound beams onto the target produces tissue effects through released energy. Regarding neurosurgical applications, tcMRgFUS has been successfully adopted as a non-invasive procedure for ablative purposes such as thalamotomy, pallidotomy, and subthalamotomy for movement disorders. Several studies confirmed the effectiveness of tcMRgFUS in the treatment of several neurological conditions, ranging from motor disorders to psychiatric disorders. Moreover, using low-frequencies tcMRgFUS systems temporarily disrupts the blood-brain barrier, making this procedure suitable in neuro-oncology and neurodegenerative disease for controlled drug delivery. Nowadays, tcMRgFUS represents one of the most promising and fascinating technologies in neuroscience. Since it is an emerging technology, tcMRgFUS is still the subject of countless disparate studies, even if its effectiveness has been already proven in many experimental and therapeutic fields. Therefore, although many studies have been carried out, many others are still needed to increase the degree of knowledge of the innumerable potentials of tcMRgFUS and thus expand the future fields of application of this technology.


Features of biological effects in cell culture in the combined exposure to ionizing radiation and copper ions.
The objective of the work was to research the features of monoand combined impact of ionizing radiation and copper salts on cell viability in vitro. Materials and methods. The studies were performed on a passaged line L929 cell culture. Copper ions of different concentrations were added to the culture medium 1 hour after exposure to irradiation at doses of 0.5; 5.0 and 10.0 Gy. There were evaluated the structure of the cell populations, the proliferative and mitotic activity and apoptosis. Results and conclusions. After incubation of the cells with copper ions of various concentrations there were seen both the activation and inhibition of proliferative and mitotic activity. Cell survival and mitotic activity were decreased in exposure to increasing doses of radiation but the polykaryocyte index was increased. After the combined in vitro exposure to ionizing radiation and copper ions there were seen morphofunctional changes of cell properties, which were not in direct proportional dependence on the dose or the copper ions concentration.


Quasiparticle chirality in epitaxial graphene probed at the nanometer scale.
Graphene exhibits unconventional two-dimensional electronic properties resulting from the symmetry of its quasiparticles, which leads to the concepts of pseudospin and electronic chirality. Here, we report that scanning tunneling microscopy can be used to probe these unique symmetry properties at the nanometer scale. They are reflected in the quantum interference pattern resulting from elastic scattering off impurities, and they can be directly read from its fast Fourier transform. Our data, complemented by theoretical calculations, demonstrate that the pseudospin and the electronic chirality in epitaxial graphene on SiC(0001) correspond to the ones predicted for ideal graphene.


Dynamics of egg counts and circulating antigen levels in a recent Schistosoma mansoni focus in northern Senegal.
Serum circulating anodic antigen (CAA) levels were compared with faecal egg counts in four subsequent population samples, randomly selected at 8-month intervals, in a recent Schistosoma mansoni focus in northern Senegal. In all four samples, antigen levels showed the same age-intensity profiles as egg counts, with a strong decline in adults. Also across population samples, a consistent relationship was found between egg counts and antigen levels. Assuming the level of CAA to be a direct reflection of worm burden, these findings support the idea that the observed egg count patterns and levels indeed reflect dynamics of worm burdens, and not of egg excretion or worm fecundity. Remarkably similar levels of both egg counts and CAA were observed in the first and last sample, collected in the same season (August--September), but 2 years apart. This suggests that a steady state of S. mansoni infection had already been reached shortly after the onset of the epidemic in this focus (3 years). Significantly lower infection levels were found in the intermediate population samples collected in January and April. The differences in infection levels across the four population samples may be because of seasonal transmission patterns. They would indicate a substantial turnover of worm populations, with an estimated average life span of only 7 months, probably less, in this recently emerged, intense S. mansoni focus.


THE STRUCTURE OF THE COLLODION MEMBRANE AND ITS ELECTRICAL BEHAVIOR : X. AN EXPERIMENTAL TEST OF SOME ASPECTS OF THE TEORELL AND MEYER-SIEVERS THEORIES OF ELECTRICAL MEMBRANE BEHAVIOR.
1. The Teorell, Meyer-Sievers theory characterizes the electrochemical behavior of membranes by their selectivity constant "A(p)" which is derived conventionally from concentration potential measurements at various concentration levels. The selectivity constant may, however, be derived also from entirely independent, different experimental data, namely base exchange studies. The constants arrived at in this second way are designated as "A(b)." The selectivity constants derived by these two methods must be in reasonable, at least semiquantitative agreement if the basic assumptions of the theory are correct. 2. The selectivity constants A(p) and A(b) were determined for eleven different sets of membranes of different electrochemical activity and of different (8.2 to 80 volume per cent) water content. 3. The potentiometric selectivity constants A(p) are in most cases several orders of magnitude greater than the corresponding A(b) values. With membranes of great porosity and high electrochemical activity the A(b) values approach at least in order of magnitude the A(p) values. 4. It is concluded that the unexpectedly large discrepancy between the A(p) and A(b) values is due to some inherent weakness of the Teorell, Meyer-Sievers theory, most likely to its neglect of any structural factors.


A clinical evaluation of isoxicam in the treatment of osteo-arthritis.
Thirteen patients with osteo-arthritis entered a 12-month open-label assessment of the efficacy and safety of a single morning dose of isoxicam 200 mg. Pain scale scores were significantly reduced and this was accompanied by improvement in most of the symptoms. No patients suffered adverse reactions considered to be definitely related to the use of isoxicam and only 3 patients reported adverse reactions (mild weight gain, stomatitis, constipation) probably related to treatment. Isoxicam 200 mg once a day was effective and well tolerated in the long-term symptomatic treatment of osteo-arthritis.


Assessment of antimicrobial and wound healing effects of Brevinin-2Ta against the bacterium Klebsiella pneumoniae in dermally-wounded rats.
Antimicrobial peptides (AMPs) are regarded as promising alternatives for antibiotics due to their inherent capacity to prevent microbial drug resistance. Amphibians are rich source of bioactive molecules, which provide numerous AMPs with various structures as drug candidates. Here, we isolated and identified a novel AMP Brevinin-2Ta (B-2Ta) from the skin secretion of the European frog, Pelophylax kl. esculentus. In vitro studies revealed that it showed broad antimicrobial activities against S. aureus, E. coli and C. albicans with low cytotoxicity to erythrocytes. Furthermore, we examined the anti-inflammation effect in vivo by using Klebsiella pneumoniae-infected Sprague-Dawley (SD) rats. The wound closure outcomes revealed that B-2Ta effectively restrained the bacterial infection at a dose of 10 times minimal inhibitory concentration (MIC) during the 14 days of the wound healing process. Ultra-structure analyses showed that B-2Ta caused structural damage to the microorganism, and bacterial culture found that the number of microbes was significantly reduced by the end of treatment. Immunohistochemistry for the inflammatory marker IL-10 and the endothelial cell marker CD31 suggested positive effects on inflammatory status and epithelial migration and angiogenesis following treatment of the infected granulation tissues with B-2Ta. These results exhibited the continuous phase of inflammation reduction and wound healing acceleration in the B-2Ta-modulated re-epithelialisation of K. pneumoniae infected rats. Taken together, these data demonstrated that B-2Ta has great potential to be developed as antibacterial agents in clinic.


Two PR-1 genes from tomato are differentially regulated and reveal a novel mode of expression for a pathogenesis-related gene during the hypersensitive response and development.
Pathogenesis-related (PR) proteins form a heterogeneous family of plant proteins that are likely to be involved in defense and are inducible by pathogen attacks. One group of PRs, represented by the subfamily PR-1, are low-molecular-weight proteins of unknown biochemical function. Here we describe the cloning and characterization of two closely related genes encoding a basic and an acidic PR-1 protein (PR1b1 and PR1a2) from tomato (Lycopersicon esculentum). We present a comparative study of the mode of transcriptional regulation of these two genes in transgenic tobacco plants using a series of promoter-GUS fusions. Unexpectedly, the chimeric PR1a2/GUS gene is not induced by pathogenic signals but instead shows constitutive expression with a reproducible developmental expression pattern. It is expressed in shoot meristems, trichomes, and cortical cells as well as in vascular and nearby tissues of the mature stem. This constitutive expression pattern may represent preemption of plant defenses against potential pathogens. Conversely, the chimeric PR1b1/GUS gene does not show any constitutive expression in the plant, but it is transcriptionally activated following pathogen attack. Upon infection by tobacco mosaic virus, the PR1b1 gene is strongly activated locally in tissues undergoing the hypersensitive response but not systemically in uninoculated tissues. Furthermore, its expression is induced by both salicylic acid and ethylene precursors, two signals that coexist and apparently mediate the activation of local defenses during the hypersensitive response. We speculate that the different mode of expression of the two genes presented here, together with that reported previously for the induction of other PR-1 genes in systemic, uninoculated tissues, may all be complementary and necessary for the plant to acquire an efficient refractory state to resist pathogen attacks.


Helminth parasites from the stomach of conger eel, Conger conger, from Madeira Island, Atlantic Ocean.
Geographic variations in the diversity and prevalence of helminth parasites of fish can provide important clues as to the relatedness of fish populations. In the present work, the stomachs of 64 conger eels, Conger conger, collected during 1999 and 2000, were examined for the presence of parasites. Four fish were infected with L3 stages of the nematode Anisakis simplex s.l. (Anisakidae), 1 with the nematode Cristitectus congeri (Cystidicolidae), 1 with the acanthocephalan Rhadinorhynchus pristis, 17 with postlarvae of Sphyriocephalus tergestinus (Eucestoda: Trypanorhyncha), and 55 with Lecithochirium spp. (Digenea: Hemiuridae). The hemiurids were the most abundant parasites, with a total of 385 individuals recovered. Strong aggregated distributions were found for both the digeneans, Lecithochirium musculus and Lecithochirium fusiforme, with variance-to-mean ratios (s2/x) and index of discrepancy (D) 13.98 and 0.672 (for L. musculus) and 8.08 and 0.90 for L. fusiforme, respectively. Intensity of L. musculus, L. fusiforme, and S. tergestinus showed significant relationships with depth of capture. Differences in number of species and prevalence were found between Madeira and the Atlantic coasts of the Iberian Peninsula.


The co.LAB Generic Framework for Collaborative Design of Serious Games: Development Study.
Serious games are increasingly used at all levels of education. However, research shows that serious games do not always fulfill all the targeted pedagogical objectives. Designing efficient and engaging serious games is a difficult and multidisciplinary process that requires a collaborative approach. Many design frameworks have been described, most of which are dedicated to the development of specific types of serious games and take the collaborative dimension into account only to a limited extent. Our aim was to create a generic serious game design framework that could be adapted to all kinds of serious games and implemented in a collaborative web platform. We combined the results of a literature review with our experience in serious game design and development to determine the basic building blocks of a collaborative design framework. We then organized these building blocks into categories and determined the features that a generic design framework should include. Finally, based on the paradigm of complex systems and systemic modelling, we created the co.LAB generic design framework and specifications to allow its implementation in a collaborative web platform. Based on a total of 10 existing design methodologies or frameworks, 23 building blocks were identified and represent the foundation of the co.LAB framework. These blocks were organized into 5 categories: "context and objectives," "game design," "mechanics," "learning design," and "assessment." The arrangement by categories provides a structure that can be visualized in multiple and complementary ways. The classical view links game and learning design while other views offer project, systemic, and process visualizations. For the implementation of the co.LAB framework in a web platform, we propose to convert the building blocks into "cards." Each card would constitute a collaborative working space for the design of the corresponding block. To make the framework adaptive, cards could be added, adapted, or removed according to the kind of serious game intended. Enhancing the visualization of relationships between cards should support a systemic implementation of the framework. By offering a structured view of the fundamental design elements required to create serious games, the co.LAB framework can facilitate the design and development of such games by virtue of a collaborative, adaptive, and systemic approach. The different visualizations of the building blocks should allow for a shared understanding and a consistent approach throughout the design and development process. The implementation of the co.LAB framework in a collaborative web platform should now be performed and its actual usability and effectiveness tested.


Unpacking COVID-19 Vaccine Attitudes: Exploring Hesitancy and Acceptance Among Undergraduate Students in Bangladesh.
Vaccine hesitancy is a significant global health concern, and mass vaccination is essential in preventing the spread of COVID-19. Undergraduate students need to be prioritized for vaccination as they continue their academic curriculum physically. However, limited research explores vaccine hesitancy and acceptance among undergraduate students in Bangladesh. Therefore, this study evaluated vaccine hesitancy and acceptance among this population. A web-based cross-sectional study was conducted between May and June 2021 using a structured questionnaire to assess COVID-19 vaccine hesitancy and acceptance among undergraduate students in Bangladesh. The Oxford Covid-19 Vaccine Hesitancy Scale was used to measure vaccine hesitancy. The study used convenient sampling. Across the country, 334 undergraduate students participated in this study on COVID-19 vaccine acceptance, with a mean age of 22.4 years. Most participants were male and unmarried, most having spent four years at university. 89.52% of participants would accept a COVID-19 vaccine if it were suggested by educational institutions or available, while 4.49% refused to receive the COVID-19 vaccine. Participants showed low levels of vaccine hesitancy, with a mean score of 10.77 on the Oxford COVID-19 Vaccine Hesitancy Scale. Most participants had a positive attitude towards receiving the vaccine, with the majority wanting to get it as soon as it becomes available. No association was found between vaccine acceptance and participants' background characteristics. Our study found a high level of vaccine acceptance among undergraduate students in Bangladesh, indicating that this group can be vaccinated quickly, significantly accelerating vaccination goals. However, further large-scale studies are recommended among vulnerable groups, including school and college students, to ensure vaccine preparedness.


A systematic analysis of experimental immunotherapies on tumors differing in size and duration of growth.
We conducted a systematic analysis to determine the reason for the apparent disparity of success of immunotherapy between clinical and experimental cancers. To do this, we performed a search of PubMed using the keywords "immunotherapy" AND "cancer" for the years of 1980 and 2010. The midspread of experimental tumors used in all the relevant literature published in 2010 were between 0.5-121 mm(3) in volume or had grown for four to eight days. Few studies reported large tumors that could be considered representative of clinical tumors, in terms of size and duration of growth. The predominant effect of cancer immunotherapies was slowed or delayed outgrowth. Regression of tumors larger than 200 mm(3) was observed only after passive antibody or adoptive T cell therapy. The effectiveness of other types of immunotherapy was generally scattered. By comparison, very few publications retrieved by the 1980 search could meet our selection criteria; all of these used tumors smaller than 100 mm(3), and none reported regression. In the entire year of 2010, only 13 used tumors larger than 400 mm(3), and nine of these reported tumor regression. Together, these results indicate that most recent studies, using many diverse approaches, still treat small tumors only to report slowed or delayed growth. Nevertheless, a few recent studies indicate effective therapy against large tumors when using passive antibody or adoptive T cell therapy. For the future, we aspire to witness the increased use of experimental studies treating tumors that model clinical cancers in terms of size and duration of growth.


Novel Redirected T-Cell Immunotherapies for Advanced Prostate Cancer.
Immunotherapy has failed to achieve durable remissions in advanced prostate cancer patients. More potent T-cell-redirecting strategies may be needed to overcome the immunologically exclusive and suppressive tumor microenvironment. Clinical trials are underway, seeking to define the optimal target for T-cell redirection, such as PSMA, PSCA, or STEAP-1, as well as the optimal strategy, with CAR or bispecific antibodies. As results continue to emerge from these trials, understanding differential toxicity and efficacy of these therapies based on their targets and functional modifications will be key to advancing these promising therapies toward clinical practice. This review provides a unique depth and breadth of perspective regarding the diverse immunotherapy strategies currently under clinical investigation for men with advanced prostate cancer.


Producing megakaryocytes from a human peripheral blood source.
Cultured megakaryocytes could prove useful in the study of human diseases, but it is difficult to produce sufficient numbers for study. We describe and evaluate the use of an expansion process to develop mature megakaryocytes from peripheral blood-derived human hematopoietic stem and progenitor cells (HSPCs). HSPCs (CD34+) were isolated from peripheral blood by positive selection and expanded using an optimal CD34+ expansion supplement. We evaluated megakaryocyte growth, maturation, and morphology in response to thrombopoietin (TPO) stimulation using flow cytometry and electron microscopy. TPO demonstrated a dose-dependent stimulatory effect on both megakaryocyte number and maturation. From 90 to 120 mL of unmanipulated peripheral blood, we isolated a mean of 1.5 × 10(5) HSPCs (1.5 × 10(3) cells/mL of whole blood). HSPCs expanded nine-fold after a 4-day culture using an expansion supplement. Expanded cells were cultured for an additional 8 days with TPO (20 ng/mL), which resulted in a 2.9-fold increase in megakaryocytic cells where 83% of live cells expressed CD41a+, a marker of megakaryocyte commitment, and 50% expressed CD42b+, a marker for megakaryocyte maturation. The expanded HSPCs responded to TPO stimulation to yield more than 1.0 × 10(6) megakaryocytes. This cell number was sufficient for morphologic studies that demonstrated these expanded HSPCs produced mature polyploid megakaryocytes capable of forming proplatelet extensions. Peripheral blood HSPCs can be expanded and differentiated into functional, mature megakaryocytes, a finding that supports the use of this process to study inherent platelet (PLT) production disorders as well as study factors that impair normal PLT production.


The role of solation-contraction coupling in regulating stress fiber dynamics in nonmuscle cells.
Serum-deprived Swiss 3T3 fibroblasts constitutively form stress fibers at their edges. These fibers move centripetally towards the perinuclear region where they disassemble. Serum stimulation causes shortening of fibers in a manner suggesting active actin-myosin-based contraction (Giuliano, K.A. and D.L. Taylor. 1990. Cell Motil. and Cytoskeleton. 16:14-21). To elucidated the role of actin-based gel structure in these movements, we examined the effects of disrupting actin organization with cytochalasin. Serum-deprived fibroblasts were microinjected with rhodamine analogs of actin or myosin II and fiber dynamics were monitored with a multimode light microscope workstation using video-enhanced contrast and fluorescence modes. When cells were perfused with greater than or equal to 3 microM cytochalasin B or 0.5 microM cytochalasin D, formation and transport of stress fibers were reversibly inhibited, and rapid and immediate shortening of existing fibers was induced. Quantification of actin and myosin II fluorescence associated with individual shortening fibers demonstrated that fluorescence per length of fiber increased for both components, suggesting sliding filament contraction. However, there was also a net loss of both actin and myosin II from fibers as they shortened, indicating a self-destructive process. Loss of material from fibers coupled with increased overlap of actin and myosin II remaining in the fibers suggested that contraction could be induced not only by increasing the force exerted by contractile motors, but also by decreasing gel structure through partial solation. Finally, cytochalasin accelerated contraction of actin-myosin-based gels reconstituted from purified proteins in the absence of myosin-based regulation, further supporting solation-contraction coupling as a possible mechanism for modulating cytoplasmic contractility (Taylor, D.L. and M. Fechheimer. 1982. Philos. Trans. R. Soc. Lond. B. Biol. Sci. 299:185-197).


CHANGE OF ACID AGGLUTINATION OPTIMUM AS INDEX OF BACTERIAL MUTATION.
A distinct difference in acid agglutination optimum for Type D (bacillus of rabbit septicemia) and its mutant form, Type G, has been observed. The optimum for Type D lies between pH 3.5 and pH 3.0. This changes during mutation, the resulting Type G mutants having in general an optimum lying between pH 4.7 and pH 3.8. The constancy of the optimum for Type D is very strict, while that for Type G is slightly less so. The variation is never so great as to cause an overlapping of optima and consequent failure of differentiation. These acid agglutination optima are in the nature of physical constants for the two types and would imply a fundamental difference in the chemical constitution of the organisms. Animal passage, far from causing a reversion of the mutant Type G to the primordial Type D form, brings about a still greater instability in the presence of H ions.


A Method to Study the Correlation Between Local Collagen Structure and Mechanical Properties of Atherosclerotic Plaque Fibrous Tissue.
The rupture of atherosclerotic plaques in coronary and carotid arteries is the primary cause of fatal cardiovascular events. However, the rupture mechanics of the heterogeneous, highly collagenous plaque tissue, and how this is related to the tissue's fibrous structure, are not known yet. Existing pipelines to study plaque mechanics are limited to obtaining only gross mechanical characteristics of the plaque tissue, based on the assumption of structural homogeneity of the tissue. However, fibrous plaque tissue is structurally heterogeneous, arguably mainly due to local variation in the collagen fiber architecture. The mechano-imaging pipeline described here has been developed to study the heterogeneous structural and mechanical plaque properties. In this pipeline, the tissue's local collagen architecture is characterized using multiphoton microscopy (MPM) with second-harmonic generation (SHG), and the tissue's failure behavior is characterized under uniaxial tensile testing conditions using digital image correlation (DIC) analysis. This experimental pipeline enables correlation of the local predominant angle and dispersion of collagen fiber orientation, the rupture behavior, and the strain fingerprints of the fibrous plaque tissue. The obtained knowledge is key to better understand, predict, and prevent atherosclerotic plaque rupture events.


Immunoglobulin Fc domain fusion to TRAIL significantly prolongs its plasma half-life and enhances its antitumor activity.
TRAIL (Apo2L) is a potent inducer of cell death. Interest in TRAIL has increased, following the observation that TRAIL can selectively kill a wide variety of human cancer cells without killing normal cells both in vitro and when grown as xenografts. Therefore, TRAIL has been proposed as a promising anticancer agent and currently is being tested in clinical trials. However, recombinant TRAIL has a very short plasma half-life, which limits its therapeutic potential. To overcome this limitation, we investigated the ability of the human IgG1 fragment crystallizable region (Fc) to enhance TRAIL stability. In this report, we show that Fc-TRAIL chimeric protein displays higher specific activity in vitro and a significantly longer half-life in mice than recombinant human TRAIL (rh-TRAIL). No short-term toxicity, especially liver toxicity, was observed. More importantly, Fc-TRAIL was much more effective in inhibiting tumor growth in a xenograft tumor model compared with rh-TRAIL. Our data suggest that fusion of Fc to TRAIL is able to improve the bioavailability and activity of TRAIL both in vitro and in vivo, and Fc-TRAIL may be explored for future clinical applications in cancer treatment and prevention.


Brazil's Cuiabá- Santarém (BR-163) Highway: the environmental cost of paving a soybean corridor through the Amazon.
Brazil's Cuiabá-Santarém (BR-163) Highway provides a valuable example of ways in which decision-making procedures for infrastructure projects in tropical forest areas need to be reformulated in order to guarantee that environmental concerns are properly weighed. BR-163, which is slated to be paved as an export corridor for soybeans via the Amazon River, traverses an area that is largely outside of Brazilian government control. A climate of generalized lawlessness and impunity prevails, and matters related to environment and to land tenure are especially unregulated. Deforestation and illegal logging have accelerated in anticipation of highway paving. Paving would further speed forest loss in the area, as well as stimulate migration of land thieves (grileiros) to other frontiers. An argument is made that the highway should not be reconstructed and paved until after a state of law has been established and it has been independently certified that sufficient governance prevails to secure protected areas and enforce environmental legislation. A waiting period is needed after this is achieved before proceeding with the highway paving. Above all, the logical sequence of steps must be followed, whereby environmental costs are assessed, reported, and weighed prior to making de facto decisions on implementation of infrastructure projects. Deviation from this logical sequence is a common occurrence in many parts of the world, especially in tropical areas.


Comparison between in vitro toxicities of tobacco- and menthol-flavored electronic cigarette liquids on human middle ear epithelial cells.
Since electronic-cigarettes (e-cigarettes) are considered less toxic than conventional tobacco smoking, the use of e-cigarettes has increased, and the market for e-cigarette liquids (e-liquids) is continuously increasing. However, many studies showed that e-cigarettes may cause various harmful effects in lung, oral and heart. In this study, we investigated the effects of e-liquids on otitis media (OM) using human middle ear epithelial cells (HMEECs). Menthol-flavored e-liquid induced significant cell death in HMEECs (IC50: 1.45 ± 0.14%) and tobacco-flavored e-liquid led to increase in inflammatory cytokine levels and higher mucin production. Flavored e-liquids decreased the mRNA levels of genes encoding epithelial sodium channels (ENaCs) in HMEECs. Apoptosis and autophagy reactions were induced by exposure of HMEECs to menthol- and tobacco-flavored e-liquids. Tobacco-flavored e-liquids caused a greater increase in the levels of autophagosome marker, LC3-II, compared to menthol-flavored e-liquids, which was followed by cell death. These results demonstrate that flavored e-liquids cause cytotoxicity via apoptosis, autophagy, inflammatory response, and mucin production in HMEECs. The flavors present in e-liquids might be a risk factor for the development of otitis media.


MIDN: a spacecraft microdosimeter mission.
MIDN (MIcroDosimetry iNstrument) is a payload on the MidSTAR-I spacecraft (Midshipman Space Technology Applications Research) under development at the United States Naval Academy. MIDN is a solid-state system being designed and constructed to measure microdosimetric spectra to determine radiation quality factors for space environments. Radiation is a critical threat to the health of astronauts and to the success of missions in low-Earth orbit and space exploration. The system will consist of three separate sensors, one external to the spacecraft, one internal and one embedded in polyethylene. Design goals are mass <3 kg and power <2 W. The MidSTAR-I mission in 2006 will provide an opportunity to evaluate a preliminary version of this system. Its low power and mass makes it useful for the International Space Station and manned and unmanned interplanetary missions as a real-time system to assess and alert astronauts to enhanced radiation environments.


Heterogeneous chemistry of organic acids on soot surfaces.
We have investigated the heterogeneous interaction between a number of carboxylic acids and soot generated from different fuel sources and formation mechanisms. A low-pressure fast flow reactor in conjunction with ion drift-chemical ionization mass spectrometry detection was employed to study uptake of monocarboxylic (benzoic, oleic, and steric) and dicarboxylic (glutaric, maleic, oxalic, and phthalic) acids on deposited soot surfaces formed by combustion of methane, propane, and kerosene. Most acids exhibited irreversible uptake on the soot surfaces and the uptake coefficient was measured in the range of 9 x 10(-4) to 1 x 10(-1) estimated based on the geometric surface areas. Brunauer, Emmett, and Teller surface areas of the deposited soot surfaces were measured and the soot bulk and surface chemical compositions were evaluated with Fourier transform infrared spectroscopy and attenuated total reflection spectroscopy. Plausible uptake mechanisms were discussed on the basis of the measured soot physiochemical properties by comparing the mono and dicarboxylic acids.


Clostridium difficile control measures: current and future methods for prevention.
Clostridium difficile is the most common cause of healthcare associated infection, and C. difficile infection (CDI) is associated with significant costs, morbidity, and mortality. One obstacle to preventing CDI is lack of high quality data on interventions to prevent CDI. This has led some to focus on areas, such as method of hand hygiene, unlikely to impact CDI incidence as much as others, such as contact precautions. In addition, existing strategies, although effective, do have limitations. Another challenge is the ability to rapidly, and accurately, diagnose CDI. Given these obstacles, new strategies to effectively prevent CDI are imperative to improve patient outcomes. Areas covered: Evidence of the interventions recommended by international scientific societies will be reviewed, as well as ongoing research on new strategies, such as screening for asymptomatic C. difficile carriage, microbiota sparing agents, bacteriocins and vaccines. Expert commentary: Current measures to prevent CDI are effective, but have significant limitations. Contact precautions and antimicrobial stewardship are likely the most effective of current prevention recommendations. Diagnostic assay utilization plays a role as well. New strategies to prevent CDI are needed, and, fortunately, several are being studied. Most likely a combination of approaches will be necessary to optimize CDI prevention.


Feeding a protein-restricted diet during pregnancy induces altered epigenetic regulation of peroxisomal proliferator-activated receptor-α in the heart of the offspring.
Impaired flexibility in the use of substrates for energy production in the heart is implicated in cardiomyopathy. We investigated the effect of maternal protein restriction during pregnancy in rats on the transcription of key genes in cardiac lipid and carbohydrate metabolism in the offspring. Rats were fed protein-sufficient or protein-restricted (PR) diets during pregnancy. Triacylglycerol concentration in adult (day 105) heart was altered by maternal protein intake contingent on post-weaning fat intake and sex. mRNA expression of peroxisomal proliferator-activated receptor (PPAR)-α and carnitine palmitoyltransferase-1 was increased by the maternal PR diet in adult, but not neonatal, offspring. PPARα promoter methylation was lower in adult and neonatal heart from PR offspring. These findings suggest that prenatal nutrition alters the future transcriptional regulation of cardiac energy metabolism in the offspring through changes in epigenetic regulation of specific genes. However, changes in gene functional changes may not be apparent in early life.


Contact network uncertainty in individual level models of infectious disease transmission.
Infectious disease transmission between individuals in a heterogeneous population is often best modelled through a contact network. This contact network can be spatial in nature, with connections between individuals closer in space being more likely. However, contact network data are often unobserved. Here, we consider the fit of an individual level model containing a spatially-based contact network that is either entirely, or partially, unobserved within a Bayesian framework, using data augmented Markov chain Monte Carlo (MCMC). We also incorporate the uncertainty about event history in the disease data. We also examine the performance of the data augmented MCMC analysis in the presence or absence of contact network observational models based upon either knowledge about the degree distribution or the total number of connections in the network. We find that the latter tend to provide better estimates of the model parameters and the underlying contact network.


A multiparametric approach to discriminate the impacts of different degrees of invasiveness of surgical procedures in sheep.
Traumatic situations in animals induce responses including pain, expressed through behavioural and physiological pathways such as inflammation, oxidative stress, hypothalamic-pituitary-adrenal (HPA) axis and autonomic nervous system. As some of these systems can also be activated during excitement and situations with a positive valence, their use as a means to assess pain response is difficult. We explored (i) how these five aforementioned pathways change in sheep exposed to various degrees of invasiveness of surgical procedures despite a therapeutic regimen and (ii) whether a multiparametric analysis that combines information from these five pathways enhances the discrimination between these situations, and estimates the relative importance of these pathways in the response. We used 24 adult sheep split into four treatments: Control (C; no fasting, no anaesthesia, no surgery), Sham (S; fasting, anaesthesia, no surgery), Rumen Canulation (R; fasting, anaesthesia, rumen cannulation) and Rumen-Duodenal-Ileum cannulation (RDI; fasting, anaesthesia, cannulation of the rumen, duodenum and ileum). Sheep' responses were measured for 5 days after surgery. When considering each behavioural or physiological pathway independently, discrimination between treatments was acceptable, its sensitivity (Se) ranging from 0% to 100%, and its specificity (Sp) ranging from 62% to 100%. The multiparametric analysis gathering information from the five pathways enhanced the effectiveness of discrimination between treatments (Se, 50% to 100%; Sp, 82% to 100%), and gave additional information on the relative contribution of each pathway to the global sheep response. Sheep global response was higher when exposed to a surgery, and increased with the surgery invasiveness. This response relied mostly on inflammation (absolute correlation for haptoglobin, 0.89), HPA (cortisol, 0.85) and behaviour (antalgic postures, 0.85). The multiparametric approach seems to be a promising tool to discriminate between different degrees of invasiveness of surgical procedures.


Osteoclasts lose innate inflammatory reactivity to metal and polymer implant debris compared to monocytes/macrophages.
Long-term aseptic failures of joint replacements are generally attributed to implant debris-induced inflammation and osteolysis. This response is largely mediated by immune and bone cells (monocytes/macrophages and osteoclasts, respectively), that in the presence of implant debris (e.g. metal particles and ions), release pro-inflammatory cytokines such as IL-1β, TNF-α, and IL-6. The relative degree to which implant debris can illicit inflammatory response(s) from osteoclasts vs monocytes/macrophages is unknown, i.e. are osteoclasts a viable target for anti-inflammatory therapy for implant debris? We investigated relative monocyte versus osteoclast inflammatory responses in a side-by-side comparison using implant debris from the perspective of both danger signaling (IL-1β) and pathogenic recognition (TNF-α) reactivity (Challenge Agents: Cobalt-alloy, Titanium-alloy, and PMMA particles, 0.9-1.8um-dia ECD and Cobalt, and Nickel-ions 0.01-0.1mM, all with and without LPS priming). Human monocytes/macrophages reacted to implant debris with >100 fold greater production of cytokines compared to osteoclast-like cells. Particulate Co-alloy challenge induced >1000 pg/ml of IL-1β and TNF-α, in monocytes and <50pg/mL IL-1β and TNF-α in osteoclasts. Cobalt ions induced >3000pg/mL IL-1β and TNF-α in monocytes/macrophages and <50pg/mL IL-1β and TNF-α in osteoclasts. The paracrine effect of supernatants from debris-treated monocytes/macrophages was capable of inducing greater osteoclastogenesis (TRAP+, p<0.06) and inflammation than direct debris challenge on osteoclasts. Our results indicate that as monocytes/macrophages differentiate into osteoclasts, they largely lose their innate immune reactivity to implant debris and thus may not be as relevant a therapeutic target as monocytes/macrophages for mitigating debris-induced inflammation.


Number of finishers and performance of age group women and men in long-distance running: comparison among 10km, half-marathon and marathon races in Oslo.
The aim of the present study was to examine the number of finishers and performance trends in 10 km, half-marathon and marathon races in Oslo. Data (total 115,725 finishers; women, n = 50,595; men, n = 65,130) from 10 km, half-marathon and marathon races in Oslo from 2008 to 2018 were analysed considering number, sex, age and running speed of finishers. The total men-to-women ratio was the smallest in the 10 km race (0.60) and the largest in the marathon (3.86) (p < 0.01, φ = 0.28). In both women and men, the slowest running speed was shown in the older age groups (p < 0.01). Based on the findings of the present study, it was concluded that relatively more women finished a 10 km and less a half-marathon and a marathon. Our results indicated that the sex difference in performance was attenuated in the longer race distances and older age groups.


Analytical model of light reflectance for extraction of the optical properties in small volumes of turbid media.
Monte Carlo simulations and experiments in tissue phantoms were used to empirically develop an analytical model that characterizes the reflectance spectrum in a turbid medium. The model extracts the optical properties (scattering and absorption coefficients) of the medium at small source-detector separations, for which the diffusion approximation is not valid. The accuracy of the model and the inversion algorithm were investigated and validated. Four fiber probe configurations were tested for which both the source and the detector fibers were tilted at a predetermined angle, with the fibers parallel to each other. This parallel-fiber geometry facilitates clinical endoscopic applications and ease of fabrication. Accurate extraction of tissue optical properties from in vivo spectral measurements could have potential applications in detecting, noninvasively and in real time, epithelial (pre)cancers.


Canonical correlation analysis for data reduction in data mining applied to predictive models for breast cancer recurrence.
Data mining methods can be used for extracting specific medical knowledge such as important predictors for recurrence of breast cancer in pertinent data material. However, when there is a huge quantity of variables in the data material it is first necessary to identify and select important variables. In this study we present a preprocessing method for selecting important variables in a dataset prior to building a predictive model.In the dataset, data from 5787 female patients were analysed. To cover more predictors and obtain a better assessment of the outcomes, data were retrieved from three different registers: the regional breast cancer, tumour markers, and cause of death registers. After retrieving information about selected predictors and outcomes from the different registers, the raw data were cleaned by running different logical rules. Thereafter, domain experts selected predictors assumed to be important regarding recurrence of breast cancer. After that, Canonical Correlation Analysis (CCA) was applied as a dimension reduction technique to preserve the character of the original data.Artificial Neural Network (ANN) was applied to the resulting dataset for two different analyses with the same settings. Performance of the predictive models was confirmed by ten-fold cross validation. The results showed an increase in the accuracy of the prediction and reduction of the mean absolute error.


Nerve influence on myosin light chain phosphorylation in slow and fast skeletal muscles.
Neural stimulation controls the contractile properties of skeletal muscle fibres through transcriptional regulation of a number of proteins, including myosin isoforms. To study whether neural stimulation is also involved in the control of post-translational modifications of myosin, we analysed the phosphorylation of alkali myosin light chains (MLC1) and regulatory myosin light chains (MLC2) in rat slow (soleus) and fast (extensor digitorum longus EDL) muscles using 2D-gel electrophoresis and mass spectrometry. In control rats, soleus and EDL muscles differed in the proportion of the fast and slow isoforms of MLC1 and MLC2 that they contained, and also in the distribution of the variants with distinct isoelectric points identified on 2D gels. Denervation induced a slow-to-fast transition in myosin isoforms and increased MLC2 phosphorylation in soleus, whereas the opposite changes in myosin isoform expression and MLC2 phosphorylation were observed in EDL. Chronic low-frequency stimulation of EDL, with a pattern mimicking that of soleus, induced a fast-to-slow transition in myosin isoforms, accompanied by a decreased MLC2 phosphorylation. Chronic administration (10 mg x kg(-1) x d(-1) intraperitoneally) of cyclosporin A, a known inhibitor of calcineurin, did not change significantly the distribution of fast and slow MLC2 isoforms or the phosphorylation of MLC2. All changes in MLC2 phosphorylation were paralleled by changes in MLC kinase expression without any variation of the phosphatase subunit, PP1. No variation in MLC1 phosphorylation was detectable after denervation or cyclosporin A administration. These results suggest that the low-frequency neural discharge, typical of soleus, determines low levels of MLC2 phosphorylation together with expression of slow myosin, and that MLC2 phosphorylation is regulated by controlling MLC kinase expression through calcineurin-independent pathways.


Impact of Minor Carbapenemases on Susceptibility to Novel β-Lactam/β-Lactamase Inhibitor Combinations and Cefiderocol in Enterobacterales.
The in vitro activity of imipenem-relebactam, meropenem-vaborbactam, ceftazidime-avibactam, and cefiderocol was evaluated against both clinical and isogenic enterobacterial isolates producing carbapenemases of the SME, NmcA, FRI, and IMI types. Ceftazidime-avibactam and meropenem-vaborbactam showed the highest activity against all tested isolates; imipenem-relebactam showed only moderate activity. All isolates remained susceptible to cefiderocol. Furthermore, avibactam and vaborbactam have greater inhibitory activity than relebactam against the tested carbapenemases. Overall, ceftazidime-avibactam, meropenem-vaborbactam, and cefiderocol were the most effective therapeutic options for treating infections caused by the tested minor carbapenemase producers.


Immunosuppression and Neoplasia.
This entire session is based upon a fairly simple assumption that the state of the host immune system is an important factor in determining whether or not malignant tumors develop and/or with what aggressiveness the tumors grow and spread after their inception. The objective of the presentation is to report to you some observations that quite definitely support an immunologic hypothesis for the etiology of cancer.


Natural history of malignant bone disease in gastric cancer: final results of a multicenter bone metastasis survey.
Bone metastasis represents an increasing clinical problem in advanced gastric cancer (GC) as disease-related survival improves. In literature, few data on the natural history of bone disease in GC are available. Data on clinicopathology, skeletal outcomes, skeletal-related events (SREs), and bone-directed therapies for 208 deceased GC patients with evidence of bone metastasis were statistically analyzed. Median time to bone metastasis was 8 months (CI 95%, 6.125-9.875 months) considering all included patients. Median number of SREs/patient was one. Less than half of the patients (31%) experienced at least one and only 4 and 2% experienced at least two and three events, respectively. Median times to first and second SRE were 2 and 4 months, respectively. Median survival was 6 months after bone metastasis diagnosis and 3 months after first SRE. Median survival in patients who did not experience SREs was 5 months. Among patients who received zoledronic acid before the first SRE, the median time to appearance of first SRE was significantly prolonged compared to control (7 months vs 4 months for control; P: 0.0005). To our knowledge, this retrospective analysis is the largest multicenter study to demonstrate that bone metastases from GC are not so rare, are commonly aggressive and result in relatively early onset of SREs in the majority of patients. Indeed, our large study, which included 90 patients treated with ZOL, showed, for the first time in literature, a significant extension of time to first SRE and increase in the median survival time after diagnosis of bone metastasis. Taken together, these data may support the beneficial effects of ZOL in GC patients.


Solving the crisis in psychopharmacological research: Cellular-membrane(s) pharmacology to the rescue?
There is an urgent need for the introduction of novel and better (i.e., improved risk-benefit profile) compounds for the treatment of major psychiatric disorders, in particular mood and psychotic disorders. However, despite increased societal awareness and a rising public and professional demand for such agents from patients and physicians, the pharmaceutical industry continues to close down its psychopharmacology research facilities in reaction to the lack of success with the search for new psychotropics. It is high time to stop this untoward trend and explore "new" lines of investigation to solve the current crisis in psychopharmacological research. In line with the prevailing molecular view in drug research in general, also in psychopharmacology mechanistic explanations for drug effects are "traditionally" looked for at the level of molecular targets, like receptors and transporters. Also, more recent approaches, although using so-called systems- and function-based approaches to model the multidimensional characteristics of psychiatric disorders and psychotropic drug action, still emphasize this search strategy for new therapeutic leads by identification of single molecules or molecular pathways. This "psychomolecular gaze" overlooks and disregards the fact that psychotropic agents usually are highly hydrophobic and amphipathic/amphiphilic agents that, in addition to their interaction with membrane-bound proteins in the form of e.g. receptors or transporters, also interact strongly with the lipid component of cellular membranes. Here we suggest to develop a program of systematic, whole-cell level based, investigation into the role of these physical-chemical cellular membrane interactions in the therapeutic action of known psychotherapeutics. This complementary yet conceptually different approach, in our opinion, will complement drug development in psychopharmacology and thereby assist in overcoming the current crisis. In this way the "old" physical theory of drug action, which antedates the current, primary molecular, paradigm may offer "new" options for lead discovery in psychopharmacological research.


Cardiopulmonary exercise testing in the evaluation of patients with occupational asthma and reactive airways dysfunction syndrome.
Cardiopulmonary exercise testing (CPET) is a well recognized tool for the functional assessment of patients with cardiovascular and pulmonary disorders. The exercise response of asthmatics has been well characterized but the exercise response of patients with occupational asthma is less well understood. In this report we describe the clinical utility of CPET by characterizing the cardiovascular and pulmonary responses to exercise in patients with occupational asthma (OA) and a closely related entity, reactive airways dysfunction syndrome (RADS). We evaluated clinical and cardiopulmonary exercise data (mean +/- SD) from patients with OA (n = 22, age = 40.1 +/- 8.9 years, 14 males) and RADS (n = 23, age = 37.7 +/- 9.7 years, 18 males) who exhibited comparable pulmonary function. Oxygen uptake, CO2 output, ventilatory parameters, cardiac hemodynamics, O2 delivery, 12 lead EKG, systemic BP, and O2 saturation were monitored at rest and during cycle ergometer exercise. Compared with the RADS group, OA patients demonstrated higher resting dead-space ventilation (41 +/- 8 vs 35 +/- 9%, p = 0.04), reduced exercise capacity (94 +/- 32 vs 122 +/- 47 W, p = 0.01), higher respiratory quotients at 50 W (0.98 +/- 0.14 vs 0.91 +/- 0.08, p = 0.04), decreased power output past attainment of the anaerobic threshold (28.1 +/- 17.1 vs 44.7 +/- 15.1 W, p = 0.002) and a strong tendency for lower anaerobic thresholds (53 +/- 9 vs 60 +/- 14% pred VO2max, p = 0.06). In the 2 groups with occupational bronchial hyperreactivity, each with mild disease severity, OA patients exhibited greater decrements in cardiovascular conditioning when compared with the RADS group, perhaps because of the more prolonged, chronic respiratory insult experienced by the OA group. These data indicate that CPET in patients with work-related bronchial hyperreactivity is of significant utility in the impairment evaluation process.


Surveillance of acute infectious gastroenteritis (1992-2009) and food-borne disease outbreaks (1996-2009) in Italy, with a focus on the Piedmont and Lombardy regions.
We describe trends in the occurrence of acute infectious gastroenteritis (1992 to 2009) and food-borne disease outbreaks (1996 to 2009) in Italy. In 2002, the Piedmont region implemented a surveillance system for early detection and control of food-borne disease outbreaks; in 2004, the Lombardy region implemented a system for surveillance of all notifiable human infectious diseases. Both systems are internet based. We compared the regional figures with the national mean using official notification data provided by the National Infectious Diseases Notification System (SIMI) and the National Institute of Statistics (ISTAT), in order to provide additional information about the epidemiology of these diseases in Italy. When compared with the national mean, data from the two regional systems showed a significant increase in notification rates of non-typhoid salmonellosis and infectious diarrhea other than non-typhoid salmonellosis, but for foodborne disease outbreaks, the increase was not statistically significant. Although the two regional systems have different objectives and structures, they showed improved sensitivity regarding notification of cases of acute infectious gastroenteritis and, to a lesser extent, food-borne disease outbreaks, and thus provide a more complete picture of the epidemiology of these diseases in Italy.


Small Nucleolar RNAs Determine Resistance to Doxorubicin in Human Osteosarcoma.
Doxorubicin (Dox) is one of the most important first-line drugs used in osteosarcoma therapy. Multiple and not fully clarified mechanisms, however, determine resistance to Dox. With the aim of identifying new markers associated with Dox-resistance, we found a global up-regulation of small nucleolar RNAs (snoRNAs) in human Dox-resistant osteosarcoma cells. We investigated if and how snoRNAs are linked to resistance. After RT-PCR validation of snoRNAs up-regulated in osteosarcoma cells with different degrees of resistance to Dox, we overexpressed them in Dox-sensitive cells. We then evaluated Dox cytotoxicity and changes in genes relevant for osteosarcoma pathogenesis by PCR arrays. SNORD3A, SNORA13 and SNORA28 reduced Dox-cytotoxicity when over-expressed in Dox-sensitive cells. In these cells, GADD45A and MYC were up-regulated, TOP2A was down-regulated. The same profile was detected in cells with acquired resistance to Dox. GADD45A/MYC-silencing and TOP2A-over-expression counteracted the resistance to Dox induced by snoRNAs. We reported for the first time that snoRNAs induce resistance to Dox in human osteosarcoma, by modulating the expression of genes involved in DNA damaging sensing, DNA repair, ribosome biogenesis, and proliferation. Targeting snoRNAs or down-stream genes may open new treatment perspectives in chemoresistant osteosarcomas.


The diagnostic value of soluble urokinase plasminogen activator receptor compared with C-reactive protein and procalcitonin in children with febrile neutropenia.
The aim of the present study was to determine the diagnostic value of soluble urokinase plasminogen activator receptor (suPAR) in pediatric patients with febrile neutropenia. A prospective case-control study was performed. Patients included 29 children with febrile neutropenia (FN) and 27 control subjects without any infection or immunosuppressive condition. Blood samples were obtained on the day of admission and on the 4th to 7th days of the hospital stay. The median (minimum-maximum) serum levels of suPAR obtained on the first day of the admission were 2.08 (0.93-9.42) and 2.22 (1.08-5.13) ng/mL for the FN group and the control group, respectively. The median serum levels of suPAR in the FN and control groups were not significantly different (P = .053). The mean serum suPAR level was significantly higher in nonsurvivors than in survivors in the FN group (P < .05). In the FN group, the area under the receiver operating characteristics curve (AUCROC) for suPAR was 0.546, but no optimum cutoff value, sensitivity, specificity, negative predictive value (NPV), or positive predictive value (PPV) was obtained. We conclude that suPAR is not useful as a diagnostic biomarker in children with febrile neutropenia; however, persistent high serum suPAR level may predict mortality in FN in children.


Inflammatory left ventricular microaneurysms as a cause of apparently idiopathic ventricular tachyarrhythmias.
We sought to investigate the arrhythmogenic role, incidence, treatment, and prognosis of inflammatory left ventricular (LV) microaneurysms in patients with apparently idiopathic ventricular tachyarrhythmias. Methods and Results-- We studied 156 consecutive patients (71 men, 85 women; mean age, 44.1+/-11.8 years) with severe ventricular arrhythmias and normal 2D echo cardiac parameters by coronary and ventricular angiography, biventricular endomyocardial biopsy, and electrophysiological study. Polymerase chain reaction was used to detect genomic sequences of enterovirus, adenovirus, Epstein Barr virus, cytomegalovirus, herpes simplex viruses, influenza A and B viruses, and hepatitis C virus in frozen endomyocardial samples. Of these patients, 15 (9.6%) showed angiographic evidence of single or multiple LV microaneurysms. All 15 patients had recurrent episodes of ventricular tachycardia with right bundle-branch block morphology, and the arrhythmias originated within or close to the aneurysms in those patients (n=6) undergoing ventricular mapping. A lymphocytic myocarditis was observed in LV biopsies of all patients and in the right ventricles of 3 patients. Polymerase chain reaction analysis was performed in 12 and viral genomes were found in 5 (42%): hepatitis C virus in 2, enterovirus in 2, and influenza virus A in 1. The patients were treated with antiarrhythmics, and cardiac function was preserved for the next 47+/-39.5 months of follow-up. No major clinical event was registered, and arrhythmias were successfully treated by antiarrhythmics. Inflammatory LV microaneurysms, often of viral origin, are a consistent cause of apparently idiopathic ventricular arrhythmias. Their prognosis so far has been benign, and aggressive therapeutic strategies have been unnecessary.


Voice Therapy Outcome-A Randomized Clinical Trial Comparing Individual Voice Therapy, Therapy in Group, and Controls Without Therapy.
A stumbling-block in voice therapy is how the patient will be able to apply the new voice technique in everyday life. Possibly this generalization process could be facilitated by giving voice therapy in group because of the natural forum for training voice-to-speech early in communication between the patients in a group setting. The aim of the study was to compare treatment results from individual voice therapy and voice therapy in group, at several time points and in comparison to patients with no voice therapy. A randomized treatment study was performed with 77 consecutive patients diagnosed with a functional voice disorder. Thirty-one patients were randomized to individual and group therapy, respectively, and 15 patients to no therapy. The assessments included standardized voice recording and registration of voice range profile (VRP), answering Voice handicap index (VHI) and visual analogue scales for self-hoarseness and self-vocal fatigue, and perceptual voice evaluation by speech-language pathologist. The assessments were performed before, direct after therapy, and three months later in all groups. The 2 therapy groups were also assessed 12 months after therapy. All VHI scores as well as the self-ratings of hoarseness and vocal fatigue, and the perceptual evaluation of voice quality and maximum VRP improved significantly in both therapy groups 3 months after treatment and at 12 months follow-up. There were no significant changes in the control group, with the exception of decreased self-rated hoarseness and increased maximum VRP. Comparisons between treatment groups showed significant larger improvement after group therapy for VHI physical subscale at 12 months, as well as significant lower VHI total score at all measurement sessions and lower subscale scores at 12 months. There were no differences between treatment groups in self-hoarseness or self-vocal fatigue and no difference in perceptual voice quality or VRP. Comparison between controls and treatment groups showed significant larger change in treatment groups from baseline to three months in VHI total and to end of therapy in functional subscale. Treatment groups also showed significant lower scores than controls at each measurement session, for VHI total and physical subscale as well as lower degree of perceptual aberration of voice quality and vocal fatigue, at three months follow-up. This study shows long-term improvement from behavioral voice therapy, particularly in a group setting. The results indicate the importance of early transfer-to-speech and late posttherapy test to capture whether the goal of voice therapy was fulfilled or not for the patients.


Management of atlantoaxial metastases with posterior occipitocervical stabilization.
The treatment of atlantoaxial spinal metastases is complicated by the region's unique biomechanical and anatomical characteristics. Patients most frequently present with pain secondary to instability; neurological deficits are rare. Recently, some authors have performed anterior approaches (transoral or extraoral) for resection of upper cervical metastases. The authors review their experience with a surgical strategy that emphasizes posterior stabilization of the spine and avoidance of poorly tolerated external orthoses such as the rigid cervical collar or halo vest. The authors performed a retrospective review of 19 consecutively treated patients with C-1 or C-2 metastases who underwent surgery at The University of Texas M. D. Anderson Cancer Center between 1994 and 2001. Visual analog pain scores were reduced at 1 and 3 months (p < 0.005, Wilcoxon signed-rank test); however, evaluation of pain at 6 months and 1 year was limited by the remaining number of surviving patients. Analgesic medication consumption was unchanged. There were no cases of neurological decline or sudden death secondary to residual or recurrent atlantoaxial disease during the follow-up period. One patient underwent revision of hardware at 11 months. The mean follow-up period was 8 months (range 1-32 months). Median survival determined by Kaplan-Meier analysis was 6.1 months (95% confidence interval 2.99-9.21). Occipitocervical stabilization provided durable pain relief and preservation of ambulatory status over the remaining life span of patients. Because of the palliative goals of surgery, the authors have not found an indication for anterior-approach tumor resection in these patients. Successful stabilization obviates the need for an external orthosis.


Is there an Ethnic Predisposition to Developing Brain Metastases (BM) in Asian Patients with Colorectal Cancer?
Most common sites of metastases in patients with colorectal cancer (CRC) include liver and lung. Brain metastases are very rare but their presence is associated with a poor prognosis and shorter survival. We report our investigation into the impact of race/ethnicity on the incidence of BM in CRC patients. We retrospectively reviewed patients diagnosed with CRC from 2010 - 2018 at a single institution and analyzed any association of development of brain metastases with race and ethnicity. Race and ethnicity were defined in accordance with federal standards set by the US Census. We identified 264 CRC patients and 76(29%) were identified as Asian. Of those 76 patients, 5(7%) developed brain metastases. All 5 patients were male and stage IV at initial diagnosis. Brain metastases was a late stage phenomenon. Median time to development of brain metastases was 29 months (Range: 26 - 33). Median overall survival after BM diagnosis was 5.5 months (Range: 4 - 11). Overall survival was longest for the patient who had both radiation and surgery. Our study showed an incidence of brain metastases of 7% in the Asian sub-population compared to the historical control of 0.6% - 3.2% in the overall population. These results at the least warrant further investigation in a larger patient population of brain metastases in CRC patients with emphasis on molecular markers.


Longitudinal associations between popularity and aggression in Chinese middle and high school adolescents.
The longitudinal associations between popularity, overt aggression, and relational aggression were assessed in middle school and high school cohorts drawn from a large urban Northwest Chinese city. The middle school (n = 880; 13.33 years.) and high school samples (n = 841; 16.66 years.) were each followed for 2 years. In the concurrent regression analyses, overt aggression was more strongly and consistently associated with popularity than relational aggression after controlling for likability. Cross-lagged analyses revealed that popularity predicted subsequent increases in overt and relational aggression throughout middle and high school whereas overt aggression at 7th and 10th grade predicted increases in popularity 1 year later. These findings provide further evidence that popularity is associated with aggression and suggest that overt and relational aggression may be a consequence rather than a contributor to popularity in Chinese adolescents. (PsycINFO Database Record (c) 2018 APA, all rights reserved).


8 ns fiber laser Q switched by the resonant saturable absorber mirror.
We demonstrate that resonant high-modulation-depth saturable absorbers allow efficient pulse shortening in Q-switched lasers. Using a 70% modulation depth resonant saturable absorber mirror we achieved 8 ns pulses that are close to the limit set by the cavity length and are, to our knowledge, the shortest pulses demonstrated to date from passively Q-switched fiber lasers.


Identification of coronary artery stenoses and poststenotic blood flow patterns using a miniature high-frequency epicardial transducer.
Intraoperative epicardial coronary Doppler ultrasound has the potential to provide anatomic and functional information. This technique has been hindered by the large size of standard transducers, but a miniature transducer is available that may fulfill the potential of coronary ultrasound. Twenty consecutive patients who were undergoing coronary artery bypass grafting were studied and compared with 9 control patients with normal coronary arteries who were undergoing routine mitral valve surgery. A miniature 6.5-MHz transducer was used to image coronary arteries and measure coronary blood flow velocities. Seventeen proximal left anterior descending and 3 right coronary artery stenoses were studied. As defined by coronary angiography (1 to 34 days before surgery), there were 13 severe stenoses (> 70%), 4 moderate stenoses (40% to 70%), 2 minor stenoses (< 40%), and 1 subtotal occlusion. Stenoses were readily identified by ultrasound. Color flow mapping demonstrated laminar flow in normal arteries and nonlaminar flow across moderate and severe stenoses. In the control patients with unobstructed arteries, peak and mean diastolic velocities were 35 +/- 2.1 and 26 +/- 1.9 cm/s with peak and mean systolic velocities of 16 +/- 1.4 and 11 +/- 0.8 cm/s, respectively. Prestenotic flow velocities were not significantly different from normal control values, but a wide range of poststenotic flow disturbances were detected. Analysis of the 20 study patients did not reveal significant differences in poststenotic compared with prestenotic flow. A subgroup analysis of 12 patients with severe left anterior descending coronary artery stenoses was performed, and reversed poststenotic systolic flow was seen in 9. Prestenotic peak and mean systolic velocities were 16.5 +/- 1.7 and 11.9 +/- 1.1 cm/s, respectively, and were significantly altered downstream of the stenoses at -22.7 +/- 17.2 and -15.9 +/- 10.9 cm/s (P < .05 and P < .01, respectively). Reversed systolic flow was seen only distal to severe left anterior descending coronary artery stenoses and did not correlate with retrograde collateral filling as determined by preoperative coronary angiography. Moderate stenoses appeared to increase both systolic and diastolic components of poststenotic flow. Epicardial Doppler ultrasound with a miniature transducer identifies coronary stenoses and associated blood flow disturbances. Compared with moderate lesions, severe stenoses demonstrated different poststenotic flow patterns. Intraoperative use of this technique may determine the hemodynamic significance of coronary stenoses.


More than race? Intragroup differences by gender and age in perceptions of police among street-identified Black men and women.
Whereas studies have documented racial differences in attitudes toward police between White and Black Americans, relatively little is known about the intragroup, gender-based variations among urban Black residents involved in criminal activity (i.e., street-identified men and women). We hypothesized Black women would be more likely to believe in police legitimacy and positive intent than men (Hypothesis 1), especially among the younger segment of the sample (Hypothesis 2). We also expected this relationship to be moderated by contact with police (Hypothesis 3) and experiences with victimization (Hypothesis 4). Using survey data, this Street Participatory Action Research project examined the direct and interactional relationships between gender, age, involuntary police contact, personal victimization, and participants' perceptions of police legitimacy and positive intent. Participants included 515 street-identified Black men (40.4%; n = 208) and women (59.6%; n = 307), ages 18-35 years, from two high-crime neighborhoods in Wilmington, Delaware. Women had significantly higher perceptions of police legitimacy than did men (Hypothesis 1). While older participants tended to have lower perceptions that the police behave with positive intent, age did not moderate the relationship between gender and perceptions of police (Hypothesis 2). The relationship between gender and perceptions of positive police intent was moderated by involuntary police contact (Hypothesis 3) and experiences of victimization (Hypothesis 4). Contrary to existing literature, prior involuntary police contact mattered more for street-identified Black women than men in predicting perceptions of police. Experiences of victimization were also more impactful for these perceptions for street-identified Black women than men. Men's perceptions of positive police intent were consistent, regardless of the frequency of police contact, whereas women's favorable perceptions declined with more police contact and victimization experiences, and they eventually became more critical of the police than their male counterparts. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Differential phosphorylation of GluN1-MAPKs in rat brain reward circuits following long-term alcohol exposure.
The effects of long-term alcohol consumption on the mitogen-activated protein kinases (MAPKs) pathway and N-methyl-D-aspartate-type glutamate receptor 1 (GluN1) subunits in the mesocorticolimbic system remain unclear. In the present study, rats were allowed to consume 6% (v/v) alcohol solution for 28 consecutive days. Locomotor activity and behavioral signs of withdrawal were observed. Phosphorylation and expression of extracellular signal-regulated protein kinase (ERK), c-Jun N-terminal kinase (JNK), p38 protein kinase and GluN1 in the nucleus accumbens, caudate putamen, amygdala, hippocampus and prefrontal cortex of these rats were also measured. Phosphorylation of ERK, but not JNK or p38, was decreased in all five brain regions studied in alcohol-drinking rats. The ratio of phospho/total-GluN1 subunit was reduced in all five brain regions studied. Those results suggest that the long-term alcohol consumption can inhibits GluN1 and ERK phosphorylation, but not JNK or p38 in the mesocorticolimbic system, and these changes may be relevant to alcohol dependence. To differentiate alcohol-induced changes in ERK and GluN1 between acute and chronic alcohol exposure, we have determined levels of phospho-ERK, phospho-GluN1 and total levels of GluN1 after acute alcohol exposure. Our data show that 30 min following a 2.5 g/kg dose of alcohol (administered intragastrically), levels of phospho-ERK are decreased while those of phospho-GluN1 are elevated with no change in total GluN1 levels. At 24 h following the single alcohol dose, levels of phospho-ERK are elevated in several brain regions while there are no differences between controls and alcohol treated animals in phospho-GluN1 or total GluN1. Those results suggest that alcohol may differentially regulate GluN1 function and ERK activation depending on alcohol dose and exposure time in the central nervous system.


Preoperative Anticoagulation Management in Everyday Clinical Practice: An International Comparative Analysis of Work-as-Done Using the Functional Resonance Analysis Method.
Preoperative anticoagulation management (PAM) is a complex, multidisciplinary process important to patient safety. The Functional Resonance Analysis Method (FRAM) is a novel method to study how complex processes usually go right at the frontline (labeled Safety-II) and how this relates to predefined procedures. This study aimed to assess PAM in everyday practice and explore the usability and utility of FRAM. The study was conducted at an Australian and European Cardiothoracic Surgery Department. A FRAM model of work-as-imagined was developed using (inter)national guidelines. Semistructured interviews with 18 involved professionals were used to develop models reflecting work-as-done at both sites, which were presented to staff for validation. Workload in hours was estimated per process step. In both centers, work-as-done differed from work-as-imagined, such as in the division of tasks among disciplines (e.g., nurses/registrars rather than medical specialists), but control mechanisms had been developed locally to ensure safe care (e.g., crosschecking with other clinicians). Centers had organized the process differently, revealing opportunities for improvement regarding patient information and clustering of clinic visits. Presenting FRAM models to staff initiated discussion on improvement of functions in the model that are vital for success. Overall workload was estimated at 47 hours per site. This FRAM analysis provided insight into PAM from the perspective of frontline clinicians, revealing essential functions, interdependencies and variability, and the relation with guidelines. Future studies are warranted to study the potential of FRAM, such as for guiding improvements in complex systems.


Alpha-chloralose as a canine anesthetic.
Since its initial description in 1893, alpha-chloralose has undergone extensive pharmacologic evaluation. It has been characterized as a compound possessing potent CNS activity and has been evaluated in humans and animal models for its therapeutic properties. Though the toxicity of the compound prohibits its use as a human therapeutic agent, it has been employed widely as an animal anesthetic in the laboratory setting. A thorough search of the literature reveals that alpha-chloralose is second only to sodium pentobarbital as the primary anesthetic agent in acute cardiovascular studies where the preservation of myocardial function is a primary consideration. The literature also shows that alpha-chloralose is the subject of much controversy. The question as to whether alpha-chloralose is a true anesthetic or an immobilizing agent with sedative-hypnotic properties has important implications in light of the current emphasis on ethics in animal research.


A randomized controlled trial comparing intrathecal morphine with transversus abdominis plane block for post-cesarean delivery analgesia.
Intrathecal morphine is an effective analgesic post-cesarean delivery; however, it may be contraindicated or unsuitable in some patients. We compared the efficacy and side effects of intrathecal morphine with an ultrasound-guided transversus abdominis plane (TAP) block in a randomized, controlled, double-blinded trial. The primary outcome was the morphine equivalents dose used in the first 24 h post-surgery. Secondary outcomes were pain scores and side effects, including pruritus, sedation, nausea and vomiting. Planned recruitment was for 90 women; however, the study was terminated early. Sixty-nine women undergoing elective cesarean delivery under spinal anesthesia were enrolled. They were randomized to receive either intrathecal morphine 100 μg plus a sham TAP block or a TAP block with 0.5% ropivacaine 1.5 mg/kg, to each side to a maximum of 20 mL. Women were assessed at 2, 6, 10, 24 h and 3 months post-spinal. Sixty-six women completed the trial. The morphine equivalents dose used in the TAP block group was greater at 24 h compared with the intrathecal morphine group (7.5 mg (95% CI 4.8-10.2) vs. 2.7 mg (95% CI 1.0-4.3), F [1, 64]=9.62, P=0.003). There was no difference at 2, 6, or 10 h. Pain scores on rest and movement were higher in the TAP block group at all times although this only reached statistical significance at 10 h (P=0.001). Nausea and vomiting (P=0.02) and pruritus (P=0.007) were lower in the TAP block group. In this trial, the TAP block was associated with greater supplemental morphine requirements and higher pain scores than intrathecal morphine but fewer opioid-related side effects. The TAP block may be a reasonable alternative when intrathecal morphine is contraindicated or not appropriate.