How can experimental endotoxemia contribute to our understanding of pain? A narrative review.
The immune system and the central nervous system exchange information continuously. This communication is a prerequisite for adaptive responses to physiological and psychological stressors. While the implicate relationship between inflammation and pain is increasingly recognized in clinical cohorts, the underlying mechanisms and the possibilities for pharmacological and psychological approaches aimed at neuro-immune communication in pain are not fully understood yet. This calls for preclinical models which build a bridge from clinical research to laboratory research. Experimental models of systemic inflammation (experimental endotoxemia) in humans have been increasingly recognized as an approach to study the direct and causal effects of inflammation on pain perception. This narrative review provides an overview of what experimental endotoxemia studies on pain have been able to clarify so far. We report that experimental endotoxemia results in a reproducible increase in pain sensitivity, particularly for pressure and visceral pain (deep pain), which is reflected in responses of brain areas involved in pain processing. Increased levels of blood inflammatory cytokines are required for this effect, but cytokine levels do not always predict pain intensity. We address sex-dependent differences in immunological responses to endotoxin, and discuss why these differences do not necessarily translate to differences in behavioral measures. We summarize psychological and cognitive factors that may moderate pain sensitization driven by immune activation. Together, studying the immune-driven changes in pain during endotoxemia offers a deeper mechanistic understanding of the role of inflammation in chronic pain. Experimental endotoxemia models can specifically help to tease out inflammatory mechanisms underlying individual differences, vulnerabilities, and comorbid psychological problems in pain syndromes. The model offers the opportunity to test the efficacy of interventions, increasing their translational applicability for personalized medical approaches.


Effects of exportin 1 on nuclear transport and meiotic resumption in porcine full-grown and growing oocytes.
Exportin 1 (XPO1) is a nuclear transport receptor involved in the nuclear export of majority proteins in somatic cells. In mammalian oocytes, however, only the presence of XPO1 has been reported at mRNA and protein levels, and the definitive functions of XPO1 and its effects on the meiotic maturation of oocytes have never been directly examined. In the present study, the expression state and the nuclear-export function of porcine XPO1 were analyzed in porcine oocytes. In addition, we investigated the effects of the overexpression and inhibition of XPO1 on meiotic regulation in full-grown and growing oocytes by mRNA injection and inhibitor treatment. Endogenous XPO1 was stably expressed in porcine oocytes during the germinal vesicle (GV) stage, and the expression of exogenous XPO1 significantly decreased the nuclear localization of XPO1 cargos, snurportin 1, and WEE1B. Inhibition of XPO1 by a specific inhibitor, leptomycin B, delayed the GV breakdown (GVBD), whereas the overexpression of XPO1 by mRNA injection accelerated the GVBD. XPO1 overexpression overcame the meiotic arrest induced by WEE1B expression in full-grown oocytes. Surprisingly, the GVBD of porcine growing oocytes, which could not resume meiosis by the maturation culture in vitro, was induced by the expression of exogenous XPO1. These results showed the presence of XPO1 and its function as a nuclear export receptor in mammalian oocytes, including growing oocytes, and they suggest that the regulation of nuclear transport has a large influence on the GV maintenance and meiotic resumption of oocytes.


Motorcycle trauma in a St Lucian hospital.
A motorcycle is a single-track, two-wheeled motor vehicle that is used worldwide for transportation. The use of the motorcycle has resulted in trauma that is associated with significant morbidity and mortality. The aim of this study is to document the pattern of motorcycle accidents and the demographics of the cyclists in St Lucia. This is a 15-month prospective study on all patients with motorcycle injuries that reported to the emergency room at the Victoria Hospital. Information on patients: age, gender helmet use, intake of alcohol/drugs before the motorcycling and mechanism of injury were obtained and filled into a prepared proforma by the attending physician. Those admitted were followed-up to know the outcome and complications of treatment. Total number of patients studied was 136 in 115 accidents, males (M) were 127 while females (F) were 9, with M:F ratio of 14.1:1.0. There were 105, 28 and 3 riders, passengers and pedestrians respectively; 87.5% of the patients were below the age of 35 years. Fifty-three per cent of the accidents occurred over the weekend. The limbs were mostly injured, constituting 81.9% of the parts of the body injured. The study revealed that young and productive males were mainly injured in motorcycle accidents and the injuries were more in the limbs. More than fifty per cent of the accidents were found to occur during the weekends and more than fifty per cent of the motorcyclists were not wearing crash helmets.


Serum iron and matrix metalloproteinase-9 variations in limbs affected by chronic venous disease and venous leg ulcers.
Severe chronic venous disease (CVD) is characterized by both dermal hemosiderin accumulation and matrix metalloproteinase (MMP) hyperactivation. The iron-driven pathway is one of the recognized mechanisms of MMP hyperactivation. To investigate the potential consequences of leg hemosiderin deposits on both iron metabolism and activation of MMPs. We contemporaneously assessed the following in the serum of the arm and ankle veins of 30 patients (C4-6) with CVD and 14 normal subjects: ferritin, transferrin, iron, percentage of transferrin iron binding capacity (%TIBC), and MMP-9. Optical microscopy examinations with Perls' staining of chronic wounds were also performed. Histology consistently revealed iron deposits. Serum ferritin, iron, and %TIBC were significantly increased in the legs affected by severe CVD compared with the arm of the same subjects or the controls. In addition, iron and %TIBC were significantly elevated in the legs of ulcer patients. The rate of activation of MMP-9 was significantly elevated in CVD. The increased iron deposition in legs affected by CVD seems to be more instable in ulcer patients, leading to iron release in the serum of the affected leg. Our data suggest the iron-driven pathway as a further mechanism for MMP hyperexpression leading to tissue lesion.


Health outcomes for Australian Aboriginal and Torres Strait Islander children born preterm, low birthweight or small for gestational age: A nationwide cohort study.
To examine health outcomes in Australian Aboriginal and Torres Strait Islander children experiencing perinatal risk and identify protective factors in the antenatal period. Baby/Child cohorts of the Longitudinal Study of Indigenous Children, born 2001-2008, across four annual surveys (aged 0-8 years, N = 1483). Children with 'mild' and 'moderate-to-high' perinatal risk were compared to children born normal weight at term for maternal-rated global health and disability, and body-mass-index measured by the interviewer. Almost one third of children had experienced mild (22%) or moderate-to-high perinatal risk (8%). Perinatal risk was associated with lower body-mass-index z-scores (regression coefficients adjusted for pregnancy and environment factors: mild = -0.21, 95% CI = -0.34, -0.07; moderate-to-high = -0.42, 95% CI = -0.63, -0.21). Moderate-to-high perinatal risk was associated with poorer global health, with associations becoming less evident in models adjusted for pregnancy and environment factors; but not evident for disability. A range of protective factors, including cultural-based resilience and smoking cessation, were associated with lower risk of adverse outcomes. Perinatal risks are associated with Australian Aboriginal and Torres Strait children experiencing adverse health particularly lower body weight. Cultural-based resilience and smoking cessation may be two modifiable pathways to ameliorating health problems associated with perinatal risk.


Childhood leukemia and road traffic: A population-based case-control study.
To assess the effect of road traffic exhaust on the risk of childhood leukemia, we carried out a population-based case-control study in the Province of Varese, northern Italy, covered by a population-based cancer registry. All 120 incident cases from 1978-97 were included in the study. Four controls per case, matched by age and gender, were sampled from population files. As index of exposure to traffic exhaust we estimated the annual mean concentration of benzene outside the home using a Gaussian diffusion model. This model uses traffic density (vehicles/day) on nearby main roads, distance between roads and residence, and information on vehicle emissions and weather conditions to estimate benzene concentration. Compared to children whose homes was not exposed to road traffic emissions (<0.1 microg/m(3) of benzene as estimated by the model), the risk of childhood leukemia was significantly higher (relative risk [RR] = 3.91; 95% confidence interval [CI] = 1.36-11.27) for heavily exposed children (over 10 microg/m(3) estimated annual average). For the intermediate exposure group (0.1-10 microg/m(3)) the relative risk was 1.51 (95% CI = 0.91-2.51). These data, considered with other available evidence, suggest that motor traffic emissions can be involved in the etiology of childhood leukemia.


Direct template matching reveals a host subcellular membrane gyroid cubic structure that is associated with SARS virus.
Viral infection can result in alterations to the host subcellular membrane. This is often reported when using transmission electron microscopy (TEM), resulting in a description of tubuloreticular membrane subcellular ultrastructure rather than a definition based on 3-D morphology. 2-D TEM micrographs depicting subcellular membrane changes are associated with subcellular SARS virion particles [Goldsmith CS, Tatti KM, Ksiazek TG et al. Ultra-structural characterization of SARS coronavirus. Emerg Infect Dis 2004; 10: 320-326]. In the present study, we have defined the 2-D membrane pattern and shape associated with the SARS virus infection. This is by using a direct template matching method to determine what the 3-D structure of the SARS virus associated host membrane change would be. The TEM image for our purposes is defined on 2-D information, such as the membrane having undergone proliferation and from pattern recognition suggesting that the membrane-described pattern is possibly a gyroid type of membrane. Features of the membrane were used to compute and match the gyroid structure with an existing 2-D TEM micrograph, where it was revealed that the membrane structure was indeed a gyroid-based cubic membrane. The 2-D gyroid computer-simulated image that was used to match the electron micrograph of interest was derived from a mathematically well-defined 3-D structure, and it is from this 3-D derivative that allows us to make inferences about the 3-D structure of this membrane. In conclusion, we demonstrate that a 3-D structure can be defined from a 2-D membrane patterned image and that a SARS viral associated membrane change has been identified as cubic membrane morphology. Possible mechanisms for this cubic membrane change are discussed with respect to viral severity, persistence and free radical production.


The roles of the rod end and the tail in vimentin IF assembly and IF network formation.
Using mutagenesis, we investigated the importance of two vimentin domains: (a) a highly conserved segment near the carboxy end of the alpha-helical rod, and (b) the tail, with which the rod end is known to interact. As judged by in vitro filament assembly and expression in transiently transfected cells lacking an endogenous vimentin network, the rod-tail interaction is not essential for 10 nm filament structure in vitro or for formation of fibrous arrays in culture. However, when mutated, amino acid residues within the rod and the tail segments can cause perturbations in IF assembly and in IF network formation. Finally, our studies show that the vimentin tail seems to play a role both in thermodynamically stabilizing IF structure in vitro and in establishing proper IF networks in vivo.


[Current perspectives in nursing informatics].
Nursing Informatics is the area of knowledge that studies the application of technological resources in teaching, in practice, in care, and in the management of care. Resources such as voice recognition, knowledge base, genoma project and even Internet have offered to Nursing a gama of possibilities for a better professional performance and better nursing care to the patient/client. This text reports and exemplifies how these resources are impacting and presenting new oportunities for teaching, research and specially for nursing care, still warns for the importance of humanized care in a high-tech scenario.


Sources of Health Information and Their Impacts on Medical Knowledge Perception Among the Saudi Arabian Population: Cross-Sectional Study.
Having a reliable source for health information is vital to build a strong foundation of knowledge, especially with the current revolution of the internet and social media, which raises many concerns regarding harmful effects on the health of the public. However, there are no studies on how the Saudi Arabian population seeks health information. Details about the most used and trusted sources of health information among the public will help health authorities and public awareness accounts on social media to effectively disseminate health information. To investigate the types of sources accessed by the Saudi Arabian population while seeking health information, as well as their level of trust in the sources and to assess the impact of these sources on their perception of medical knowledge and health decision-making. A cross-sectional study was conducted to meet the objectives. The study population included both men and women who were aged 16 years or more and visited primary care clinics at King Khalid University Hospital. Four hundred and thirteen participants were sampled using the simple random method, and a self-administered questionnaire was used to collect data. The data were analyzed using SPSS software (IBM Corp, Armonk, New York, USA). A total of 413 participants were included in this study, and of these, 99 (24.0%) were males and 206 (49.9%) had a bachelor's degree. Doctors were chosen as the first source of information by 87.6% (283/323) of the participants, and they were completely trusted by most of the population (326/411, 79.3%). The second most commonly used source was pharmacists (112/194, 57.7%), and they were partially trusted by 41.4% (159/384) of the participants. Internet searches, social media, and traditional medicine were not prioritized by most of the participants as the first or second source of health information. The majority of the participants did not trust information obtained from social media, and WhatsApp was the most untrusted source. Almost half of the respondents (197/413, 47.7%) acknowledged that various sources of information can often help them understand their health problems. However, the majority disagreed on substituting a doctor's prescription with information obtained from the internet or a friend or relative. Although physicians were preferred and highly trusted, internet sources appeared to impact the medical knowledge of the population. The population still preferred to use internet search to obtain health information prior to a doctor's visit.


Identification of strain-specific and group-reactive antigenic determinants on the Karp, Gilliam and Kato strains of Rickettsia tsutsugamushi.
Hybridoma antibodies (Hab) were prepared against the Karp, Gilliam and Kato strains of Rickettsia tsutsugamushi and were examined for homologous and heterologous reactivity using an indirect immunofluorescence assay. Strain-specific Hab demonstrated homologous IFA titers ranging from 1/320 to 1/1,280 and did not react (less than 1/10) with the heterologous strains. The cross-reactive Hab generally reacted equally with all three strains in the scrub typhus group; however, there were some Hab that reacted with only one of the two heterologous strains tested. The Hab also were examined in enzyme-linked immunosorbent assays with scrub typhus antigens eluted from SDS-polyacrylamide gels. Most Hab reacted with either one or several of the six eluted antigens detected with a polyclonal immune serum. It was also observed that strain-specific and cross-reactive Hab sometimes reacted with the same antigen, suggesting the existence of multiple antigenic determinants in one electrophoretic peak. The data suggest that strain-specific Hab can be used in the indirect immunofluorescence assay to identify isolates of R. tsutsugamushi without the cross-reactions usually observed with polyclonal antisera, and that they are useful probes for detection and analysis of rickettsial antigens.


Interstitial pneumonia with autoimmune features and undifferentiated connective tissue disease: Our interdisciplinary rheumatology-pneumology experience, and review of the literature.
Interstitial lung diseases (ILDs) are a heterogeneous group of disorders characterized by inflammation and/or fibrosis of the lungs, varying from idiopathic interstitial pneumonias to secondary variants, including the ILDs associated to connective tissue diseases (CTDs). In addition, a number of patients are recognized as unclassifiable ILD (U-ILD), because of the inability to reach a definite diagnosis; some of them show autoimmune manifestations not fulfilling the classification criteria of a given CTD. The term interstitial pneumonia with autoimmune features (IPAF) has been recently proposed for this particular ILD subset. Here, we report our experience resulting from the integrated - pneumology/rheumatology - approach to patients with suspected ILDs or CTDs referred to our university-based Center for the Rare Pulmonary Diseases and Rheumatology Unit, from January 2009 to June 2015, with particular attention to the above-mentioned U-ILD, IPAF, and undifferentiated connective tissue disease (UCTD). The comparative analysis of these clinical variants was carried out; moreover, the observed findings were compared with the results of the updated review of the literature. After the first clinical assessment, the U-ILD were identified in 50 patients; afterwards, on the basis of clinico-serological and radiological findings U-ILD group was subdivided into 2 subgroups, namely U-ILD without any clinical extra-thoracic manifestations and/or immunological alterations (15 pts) and IPAF according to the above-mentioned classification criteria (35 pts). Patients with either IPAF or U-ILD were compared with a series of 52 stable UCTD (disease duration ≥3 years), followed at our Rheumatology Unit. Some important differences were evidenced among the 3 series of U-ILD, IPAF, and UCTD: firstly, female gender was more frequent in patients with UCTD (86%) or IPAF (69%) compared with U-ILD (60%) or idiopathic pulmonary fibrosis (24%; p=0.001). In addition, UCTD patients were younger and showed longer disease duration. More interestingly, both UCTD and IPAF series show a comparable prevalence of various clinical manifestations, with the exception of the interstitial lung involvement detectable in a very small percentage of UCTD patients. Concordantly, the review of the literature evidenced two main subsets of U-ILD, one is characterized by isolated unclassifiable interstitial pneumonia and another one composed by subjects with clinically prevalent lung involvement in the setting of not definite CTD, the recently proposed IPAF. We hypothesize that IPAF and UCTD might represent two clinical variants of the same systemic autoimmune disorders. The marked difference regarding the prevalence of ILD, which is the clinical hallmark of IPAF but very rare in UCTD, may at least in part reflect a selection bias of patients generally referred to different specialist centers, i.e. pneumology or rheumatology, according to the presence/absence of clinically dominant ILD, respectively. Well-integrated, interdisciplinary teams are recommended for the assessment and management of these patients in the clinical practice. Finally, the cooperation between multidisciplinary groups with different experiences may be advisable for a validation study of the proposed nomenclature and classification criteria of these indefinable ILD/CTD variants.


Sonographic Evaluation of Medial Iliac Lymph Nodes-to-Aorta Ratio in Dogs.
Medial iliac lymph nodes drain many districts and are easy to identify during an ultrasound examination of the abdomen. Since there are no reference values for their size in healthy dogs, the aim of this work was to evaluate the size of the medial iliac lymph nodes by using a ratio with the aortic diameter and find a reference range. The population was divided into group A (healthy dogs) and group B, with diseases of the medial iliac lymph nodes. The ratio of length, height and thickness of the medial iliac lymph nodes with the diameter of the aorta were calculated and underwent statistical analysis, p < 0.05 was considered statistically significant. Sixty-three patients were enrolled in group A, and 37 in group B. Significant differences were found between the ratio of sick and healthy patients and neoplastic and healthy patients. No significant difference was found between healthy and inflammatory patients. The best cut-off value to discriminate sick and healthy patients was 0.57, with a sensitivity of 78% and a specificity of 71%. The cut-off value of neoplastic and healthy patients was 0.69, with a sensitivity of 89.47% and a specificity of 84.13%. This value is highly predictive of neoplasia.


Increased proportions of γδ T lymphocytes in atypical SCID associate with disease manifestations.
Severe combined immunodeficiencies (SCID) comprise a group of genetic diseases characterized by abrogated development of T lymphocytes. In some case reports of atypical SCID patients elevated proportions of γδ T lymphocytes have been reported. However, it is unknown whether these γδ T cells modulate or reflect the patient's clinical phenotype. We investigated the frequency of elevated γδ T cell proportions and associations with clinical disease manifestations in a cohort of 76 atypical SCID patients. Increased proportions of γδ T lymphocytes were present in approximately 60% of these patients. Furthermore, we identified positive correlations between elevated proportions of γδ T cells and the occurrence of CMV infections and autoimmune cytopenias. We discuss that CMV infections might trigger an expansion of γδ T lymphocytes, which could drive the development of autoimmune cytopenias. We advocate that atypical SCID patients should be screened for elevated proportions of γδ T lymphocytes, CMV infection and autoimmune cytopenias.


Occupational protein contact dermatitis.
Occupational contact dermatitis is generally caused by haptens but can also be induced by proteins causing mainly immunological contact urticaria (ICU); chronic hand eczema in the context of protein contact dermatitis (PCD). In a monocentric retrospective study, from our database, only 31 (0.41%) of patients with contact dermatitis had positive skin tests with proteins: 22 had occupational PCD, 3 had non-occupational PCD, 5 occupational ICU and 1 cook had a neutrophilic fixed food eruption (NFFE) due to fish. From these results and analysis of literature, the characteristics of PCD can be summarized as follows. It is a chronic eczematous dermatitis, possibly exacerbated by work, suggestive if associated with inflammatory perionyxix and immediate erythema with pruritis, to be investigated when the patient resumes work after a period of interruption. Prick tests with the suspected protein-containing material are essential, as patch tests have negative results. In case of multisensitisation revealed by prick tests, it is advisable to analyse IgE against recombinant allergens. A history of atopy, found in 56 to 68% of the patients, has to be checked for. Most of the cases are observed among food-handlers but PCD can also be due to non-edible plants, latex, hydrolysed proteins or animal proteins. Occupational exposure to proteins can thus lead to the development of ICU. Reflecting hypersensitivity to very low concentrations of allergens, investigating ICU therefore requires caution and prick tests should be performed with a diluted form of the causative protein-containing product. Causes are food, especially fruit peel, non-edible plants, cosmetic products, latex, animals.


[Lumbar total disc replacement. Short-term results].
Motion-preservation technologies for spinal disorders have evolved and come into use in the last decade. Three principal systems are currently available: total disc replacement, posterior neutralisation transpedicular system and interspinous implants. The aim of this retrospective study was to evaluate our group of lumbar total disc replacements at a follow-up of 2 years. A total of 42 disc prostheses were implanted in 37 patients. Of these, 31 with 35 artificial discs were followed up for 2 years. There were 11 men and 20 women with an average age of 42.9 years (range, 21 to 61 years). The indication for surgery was lumbar disc pain without radicular syndrome and contraindications included advanced degenerative facet joint disease and obesity with a body mass index over 30. Surgery was carried out through the pararectal retroperitoneal approach. Early and late complications were recorded. The group evaluation was based on radiological outcomes, and VAS and ODI scores reported by the patients at 6 weeks, and 3, 6, 12 and 24 months after surgery. The average operative time was 68 minutes (range, 36 to 120 min) for single-level lumbar total disc replacement and 92 minutes (range, 72 to 130 min) for two-level procedures. The average hospital stay was 5.2 days (range, 3 to 12). Both keels of the prosthesis were in the exact center in 25 cases, they were shifted laterally in nine cases up to 2 mm and in one case more than 2 mm. Horizontal rotation of the prosthesis was seen in two patients, but not more than 5 degrees to the left. There was no disc loosening or subsidence, and no acceleration of adjacent segment degeneration. Two patients showed heterotopic ossification. Subjective evaluation was recorded as marked improvement in 15, partial improvement in 11 and no change in five patients. None of the patients reported deterioration. Low back pain assessed by the VAS score had an average value of 66.3 before surgery and 14.1 at 2 years after surgery. The average pre-operative ODI value was 48.9 and that at 2 years post-operatively was 24.5. Pain relief evaluated by the VAS score in our study is comparable with or slightly better than is reported by the other authors. Some recorded average values for lumbago were 74 before surgery and 35 at 2 years of follow-up, or 62.3 before and 25.4 at 2 years after surgery, while our patients had the average VAS score of 66.3 before surgery and that of 18.4 at 2 years after surgery. The ODI values in our group were similar to those of other authors. When we compare this group with the group of our patients who were treated by spinal fusion surgery, the outcomes at 1 year are better in the total disc replacement group, as shown by the VAS for lumbago of 17.8 and ODI of 24.5 in the former versus the respective values of 18.1 and 29.0 in the latter group. Based on the results it can be concluded that total disc replacement is an efficient method of treating degenerative intervertebral disc disease of the lumbar spine in young, active and motivated patients with no posterior spinal structure degeneration.


Modified Austin procedure for correction of hallux valgus.
The Austin osteotomy is a widely accepted method for correction of mild and moderate hallux valgus. In view of publications by Kitaoka et al. in 1991 and by Mann and colleagues, a more radical lateral soft tissue procedure was added to the originally described procedure. From September 1992 to January 1994, 85 patients underwent an Austin osteotomy combined with a lateral soft tissue procedure to correct their hallux valgus deformities. Seventy-nine patients (94 feet) were available for follow-up. The average patient age at the time of the operation was 47.1 years, and the average follow-up was 16.2 months. The average preoperative intermetatarsal angle was 13.9 degrees, and the average hallux valgus angle was 29.7 degrees. After surgery, the feet were corrected to an average intermetatarsal angle of 5.8 degrees and an average hallux valgus angle of 11.9 degrees. Sesamoid position was corrected from 2.1 before surgery to 0.5 after surgery. The results were also graded according to the Hallux Metatarsophalangeal Interphalangeal Score, and the functional and cosmetic outcomes were graded by the patient. Dissection of the plantar transverse ligament and release of the lateral capsule repositioned the tibial sesamoid and restored the biomechanics around the first metatarsophalangeal joint. There was no increased incidence of avascular necrosis of the first metatarsal head compared with the original technique.


Characterization of the aldolase B intronic enhancer.
The aldolase B gene is transcribed at a high level in the liver, kidney, and small intestine. This high level of gene expression results from cooperation between a weak but liver-specific promoter and an intronic activator. A deletional study of this activator present in the first intron allowed us to ascribe the maximal enhancer function to a 400-base pair (bp) fragment (+1916 to + 2329). This enhancer is highly liver-specific and enhances the activity of heterologous minimal promoters in a position and distance-independent fashion in transiently transfected Hep G2 hepatoma cells. The aldolase B enhancer is composed of two domains, a 200-bp module (Ba) inactive by itself but which synergizes with another 200-bp module (Bb) that alone retains 25% of the total enhancer activity. The Bb sequence is 76% homologous between human and rat genes and contains several binding sites for liver-enriched nuclear factors. By electrophoretic mobility shift assays, we demonstrated that elements 5 and 7 bind hepatic nuclear factor 1 (HNF1), whereas element 2 binds hepatic nuclear factor 4 (HNF4). A functional analysis of the enhancer whose elements have been mutated demonstrated that mutation of any of the HNF1 sites totally suppressed enhancer activity, whereas mutation of the HNF4-binding site reduced it by 80%.


Fast, sensitive, and inexpensive alternative to analytical pigment HPLC: quantification of chlorophylls and carotenoids in crude extracts by fitting with Gauss peak spectra.
Quantification of pigments in complex mixtures is an important task in the physiology of photosynthetic organisms, because pigment composition differs depending on the species, tissue, and physiological state. Currently available methods, however, are either limited to very few pigments (classical UV/vis spectroscopic methods), or they are time-consuming, labor intensive, or costly (e.g., HPLC). Here we describe a UV/vis spectrophotometric method that is capable of a rapid (approximately 1 min/sample) and inexpensive (<1 euro/sample) quantification of more than a dozen pigments in a crude extract, which means it is suitable for high-throughput screening applications. A detection limit of <1 pmol for each pigment allows for determining the pigment composition in only 0.5 microg of lyophilized leaves or algae. The method is based on the description of each pigment spectrum by a series of Gaussian peaks. A sample spectrum is then fitted by a linear combination of these "Gauss peak spectra" including an automatic correction of wavelength inaccuracy, baseline instability, sample turbidity, and effects of temperature/water content. Here we present the Gauss peak spectra from 350 to 750 nm for acetone solutions of all chlorophyll and carotenoid derivatives that are abundant (including conditions of Cd, Cu, or Zn stress) in leaves of higher plants, Euglena, brown algae, and various cyanobacteria like Anabaena and Trichodesmium: [Mg]-Chl a, b, c1, c2; pheophytin a, b; [Cd]-Chl a, b; [Cu]-Chl a, b; [Zn]-Chl a, b; antheraxanthin, aurochrome, beta-carotene, beta-cryptoxanthin, cis- and trans-canthaxanthin, diadinochrome (=diadinoxanthin 5,6-epoxide), cis- and trans-diadinoxanthin, diatoxanthin, cis- and trans-echinenone, fucoxanthin, lutein, myxoxanthophyll, neoxanthin, violaxanthin, and all three stereoisomers of zeaxanthin in acetone. We present extensive tests of our new quantification method for determining optimal and limiting conditions of its performance and for comparison with previous methods. Finally, we show application examples for Thlaspi fendleri (Chlorophyta), Euglena gracilisc (Euglenophyta), Ectocarpus siliculosus (Phaeophyta), and Trichodesmium erythraeum IMS101 (cyanobacteria).


Risk Factors and Prevalence of QTc Prolongation in Adult Burn Patients Receiving Methadone.
Methadone is an opioid commonly used for acute pain management in burn patients. One adverse effect of methadone is QTc interval prolongation, which may be associated with adverse cardiac outcomes. There is currently a paucity of data regarding risk of QTc prolongation in burn patients taking methadone and a lack of evidence-based recommendations for monitoring strategies in this population. The study objective was to determine the prevalence, risk factors, and cardiac outcomes related to methadone-associated QTc prolongation in adult burn patients. A total of 91 patients were included and were divided into groups according to maximum QTc. QTc prolongation was defined as greater than or equal to 470 ms (males) or 480 ms (females). There were no differences between groups regarding patient-specific risk factors, baseline QTc, or time to longest QTc. Patients in the prolonged QTc group had a higher rate of cardiac events (44% vs 9%; P < .001), higher median (IQR) change from baseline to longest QTc (61 ms [18,88] vs 23 ms [13,38]; P < .001), higher median (IQR) total daily dose of methadone (90 mg [53,98] vs 53 mg [30,75]; P = .004), and longer median (IQR) length of stay (53 [33,82] vs 35 [26,52] days; P = .008). QTc prolongation in burn patients was associated with increased methadone dose and resulted in a higher rate of cardiac events. This study was the first of its kind to look at risk factors and cardiac outcomes associated with methadone use in burn patients.


Protection against lethal leptospirosis after vaccination with LipL32 coupled or coadministered with the B subunit of Escherichia coli heat-labile enterotoxin.
Leptospirosis, a worldwide zoonosis, lacks an effective, safe, and cross-protective vaccine. LipL32, the most abundant, immunogenic, and conserved surface lipoprotein present in all pathogenic species of Leptospira, is a promising antigen candidate for a recombinant vaccine. However, several studies have reported a lack of protection when this protein is used as a subunit vaccine. In an attempt to enhance the immune response, we used LipL32 coupled to or coadministered with the B subunit of the Escherichia coli heat-labile enterotoxin (LTB) in a hamster model of leptospirosis. After homologous challenge with 5× the 50% lethal dose (LD(50)) of Leptospira interrogans, animals vaccinated with LipL32 coadministered with LTB and LTB::LipL32 had significantly higher survival rates (P < 0.05) than animals from the control group. This is the first report of a protective immune response afforded by a subunit vaccine using LipL32 and represents an important contribution toward the development of improved leptospirosis vaccines.


3D Cancer Migration Assay with Schwann Cells.
In pancreatic cancer, neural invasion is one of the most common paths of cancer dissemination. Classically, cancer cells actively invade nerves and cause local recurrence and pain. Three-dimensional (3D) neural migration assay has become a standard tool for scientists to study neural invasion by confronting the involved cell types. This protocol introduces Schwann cells, i.e., the most prevalent cell type in peripheral nerves, in a novel heterotypic, glia-cancer-neuron, 3D migration assay for assessing their relevance in the early pathogenesis of neural invasion. Particularly, this assay allows the monitoring of the early Schwann cell migratory activity.


The practice annual report: post mortem or prescription?
While a minority of general practices have been producing annual reports for a number of years one of the implications of the government's new contract is that this process will become much more widespread. To date the majority of reports have concentrated on looking back at past activity rather than on looking forward. In this article a mechanism is outlined for turning the annual report into a vehicle for improving participation; for enabling performance review; and for providing direction for the future. Central to this process is the incorporation of a number of objectives into the report. Objectives should relate to the resources of the practice, the activities of the practice and the results which the practice hopes to achieve. Methods for deriving appropriate objectives are described.


[A centering guide for the gamma camera].
A device for centering a gamma-camera indicator is described. It permits the use of available medical coaches instead of a table with a transparent top. The device can be used for centering an indicator (when it is fixed at the low end of a gamma-camera) on a required area of the patient's body.


Effects of physical exercise in the perception of life satisfaction and immunological function in HIV-infected patients: Non-randomized clinical trial.
there is a lack of research about the relationship between exercise and the psychological well-being of HIV-infected (Human Immunodeficiency Virus) patients. the objective of this study was to investigate the influence of a physical training program on life satisfaction and on the immunological function in HIV-patients. a total of 29 HIV-seropositive patients [age: 45 ± 2 yrs; Body Mass Index (BMI): 22.8 ± 1.0 kg/m² ; TCD4: 20.5 ± 2.0%] were allocated to the control (CG, n=10) and to the experimental groups (EG, n=19). The EG participated in an exercise program combining aerobic, strength, and flexibility exercises for a period of 12 weeks [3 times/week of 30 min of aerobic exercise (workload corresponding to 150 bpm-PWC150); 50 min of strength exercises (3 sets of 12 repetitions in 5 exercises at 60-80% 12 RM); and 10 min of flexibility exercises (2 sets of 30 seconds at maximal range of motion of 8 exercises)]. The immunological function was assessed by flow citometry [absolute and relative TCD4 cells counting] and the life satisfaction was assessed by the Life Satisfaction Index (LSI). the analysis of variance (ANOVA) showed no significant differences for relative and absolute CD4 T counts for both groups, however, a slight enhancement trend in the EG [16%, p=0.19] was observed. There was a significant improvement of LSI [approximately 15%; P<0.05] in EG, but not for CG. a physical activity program of moderate intensity improved life satisfaction perception in HIV-infected patients with no immunological function impairment.


Role of acamprosate in sensorineural tinnitus.
Acamprosate with dual mechanism of action as glutamate antagonist and GABA agonist can be a potential target to decrease the severity of sensorineural tinnitus. (1)To study the effectiveness of acamprosate in providing subjective relief and objective improvement in patients having tinnitus of sensorineural origin. (2) To evaluate the adverse events related to the use of acamprosate and also determine the change in quality of life (QOL) parameters. The study was randomized double-blind, placebo controlled, crossover. Forty adult subjects (>18 years of age), of either sex with tinnitus of sensorineural origin, were administered either acamprosate 333 mg TDS or matched placebo for a period of six weeks followed by a washout period of one week. Drug therapy was switched for another six weeks in consonance with the crossover design. The effect of acamprosate and placebo on subjective relief and objective improvement was evaluated by using modified tinnitus severity, QOL scores and audiometry with tinnitus matching in frequency and loudness. At the end of the study, the drug had shown a statistically significant improvement in reducing the tinnitus score in 92.5% of the patients and placebo with an improvement in 12.5% of the patients. The drug was well tolerated without any serious drug reactions. Acamprosate is an effective drug in treating the severity of sensorineural tinnitus without causing much of the side effects.


Photoacoustic lymphangiography exhibits advantages over near-infrared fluorescence lymphangiography as a diagnostic tool in patients with lymphedema.
Photoacoustic imaging is a new technique that can evaluate the vascular system using photoacoustic effects. The present study compared the ability of the new photoacoustic lymphangiography (PAL) method and more standard near-infrared fluorescence (NIRF) to image the lymphatic system in patients with secondary lymphedema after gynecological cancer surgery. Patients with secondary lymphedema in the lower extremities after gynecologic cancer surgery, who were assessed using PAL between May 2018 and January 2019, were recruited. NIRF was performed first using 5.0 mg/mL of indocyanine green injected using a 0.2-cc 30-gauge needle. Correlations between NIRF and PAL findings on patient images were subsequently examined. Seventeen patients with secondary lymphedema were enrolled. The mean age of the patients was 61 ± 11 years. The imaging sites were the medial lower leg in 15 patients, the posterior lower leg in 9 patients, the lateral lower leg in 7 patients, the medial knee in 4 patients, and other areas in 3 patients. A total of 38 pictures were obtained. Five distinct lymphatic patterns were observed over the entire sample using PAL: straight, winding, spiderweb, nebulous, and black-out pattern. Eighteen of the 24 limbs (75%) that exhibited a linear pattern in NIRF exhibited a straight pattern in PAL, and 19 of the 20 limbs (95%) that exhibited a splash pattern in NIRF exhibited a winding or spiderweb pattern in PAL. Eight limbs exhibiting diffuse patterns without linear or splash patterns with NIRF were all nebulous or black-out patterns in PAL. This suggests that more severe lymphatic degeneration was associated with poorer visualization in PAL. NIRF plays an important role in lymphedema treatment. In the present study, various PAL patterns were compared with those observed using NIRF. PAL provided clearer images including transectional views, which were not available using NIRF, and may promote further understanding of the changes in the lymphatic structure and function in patients with secondary lymphedema.


Efficient estimation for large-scale linkage disequilibrium patterns of the human genome.
In this study, we proposed an efficient algorithm (X-LD) for estimating linkage disequilibrium (LD) patterns for a genomic grid, which can be of inter-chromosomal scale or of small segments. Compared with conventional methods, the proposed method was significantly faster, dropped from O(nm2) to O(n2m)-n the sample size and m the number of SNPs, and consequently we were permitted to explore in depth unknown or reveal long-anticipated LD features of the human genome. Having applied the algorithm for 1000 Genome Project (1KG), we found (1) the extended LD, driven by population structure, universally existed, and the strength of inter-chromosomal LD was about 10% of their respective intra-chromosomal LD in relatively homogeneous cohorts, such as FIN, and to nearly 56% in admixed cohort, such as ASW. (2) After splitting each chromosome into upmost of more than a half million grids, we elucidated the LD of the HLA region was nearly 42 folders higher than chromosome 6 in CEU and 11.58 in ASW; on chromosome 11, we observed that the LD of its centromere was nearly 94.05 folders higher than chromosome 11 in YRI and 42.73 in ASW. (3) We uncovered the long-anticipated inversely proportional linear relationship between the length of a chromosome and the strength of chromosomal LD, and their Pearson's correlation was on average over 0.80 for 26 1KG cohorts. However, this linear norm was so far perturbed by chromosome 11 given its more completely sequenced centromere region. Uniquely chromosome 8 of ASW was found most deviated from the linear norm than any other autosomes. The proposed algorithm has been realized in C++ (called X-LD) and is available at https://github.com/gc5k/gear2, and can be applied to explore LD features in any sequenced populations.


Pediatric Glioma at the Optic Pathway and Thalamus.
Gliomas are the most common pediatric tumors of the central nervous system. In this review, we discuss the clinical features, treatment paradigms, and evolving concepts related to two types of pediatric gliomas affecting two main locations: the optic pathway and thalamus. In particular, we discuss recently revised pathologic classification, which adopting molecular parameter. We believe that our review contribute to the readers' better understanding of pediatric glioma because pediatric glioma differs in many ways from adult glioma according to the newest advances in molecular characterization of this tumor. A better understanding of current and evolving issues in pediatric glioma is needed to ensure effective management decision.


Contact dermatitis and adverse oral mucous membrane reactions related to the use of dental prostheses.
The latest trends in the use and composition of dental prostheses have been reviewed, and 66 patients referred by dermatologists and odontologists patch tested. The allergen series used were: TRUE Test standard series; Chemotechnique dental screening series; specially prepared metals series. The allergens found to be positive, in order of frequency, were: nickel, cobalt, potassium dichromate, rhodium, palladium, mercury, beryllium, methyl methacrylate, copper and zinc.


Modulation of neural activities by Na, K-ATPase alpha 2 subunit through functional coupling with transporters.
Na,K-ATPase is the active transporter that maintains Na+ and K+ gradients across the cell membrane. The enzyme is composed of Alpha and Beta subunits and there are four Alpha and three Beta subunit isoforms. The enzyme is responsible for various physiological processes including housekeeping function of animal cells, and specific function has been allocated to each isoform during evolution. We found that the Na,K-ATPase Alpha2 subunit functions in concert with various transporters during ontogeny by analyses of phenotypes of mice with defective Alpha2 subunit. The homozygous mice die soon after birth without breathing and the heterozygous mice show late-onset obesity. We summarize here the specific functions of the Na,K-ATPase Alpha2 subunit and physiological roles in vivo.


Molecular mechanisms and kinetics between DNA and DNA binding ligands.
Mechanical properties of single double-stranded DNA (dsDNA) in the presence of different binding ligands were analyzed in optical-tweezers experiments with subpiconewton force resolution. The binding of ligands to DNA changes the overall mechanic response of the dsDNA molecule. This fundamental property can be used for discrimination and identification of different binding modes and, furthermore, may be relevant for various processes like nucleosome packing or applications like cancer therapy. We compared the effects of the minor groove binder distamycin-A, a major groove binding alpha-helical peptide, the intercalators ethidium bromide, YO-1, and daunomycin as well as the bisintercalator YOYO-1 on lambda-DNA. Binding of molecules to the minor and major groove of dsDNA induces distinct changes in the molecular elasticity compared to the free dsDNA detectable as a shift of the overstretching transition to higher forces. Intercalating molecules affect the molecular mechanics by a complete disappearance of the B-S transition and an associated increase in molecular contour length. Significant force hysteresis effects occurring during stretching/relaxation cycles with velocities >10 nm/s for YOYO-1 and >1000 nm/s for daunomycin. These indicate structural changes in the timescale of minutes for the YOYO-DNA and of seconds for the daunomycin-DNA complexes, respectively.


Simulating plasticity as a framework for understanding habitat selection and its role in adaptive capacity and extinction risk through an expansion of CDMetaPOP.
Adaptive capacity can present challenges for modelling as it encompasses multiple ecological and evolutionary processes such as natural selection, genetic drift, gene flow and phenotypic plasticity. Spatially explicit, individual-based models provide an outlet for simulating these complex interacting eco-evolutionary processes. We expanded the existing Cost-Distance Meta-POPulation (CDMetaPOP) framework with inducible plasticity modelled as a habitat selection behaviour, using temperature or habitat quality variables, with a genetically based selection threshold conditioned on past individual experience. To demonstrate expected results in the new module, we simulated hypothetical populations and then evaluated model performance in populations of redband trout (Oncorhynchus mykiss gairdneri) across three watersheds where temperatures induce physiological stress in parts of the stream network. We ran simulations using projected warming stream temperature data under four scenarios for alleles that: (1) confer thermal tolerance, (2) bestow plastic habitat selection, (3) give both thermal tolerance and habitat selection preference and (4) do not provide either thermal tolerance or habitat selection. Inclusion of an adaptive allele decreased declines in population sizes, but this impact was greatly reduced in the relatively cool stream networks. As anticipated with the new module, high-temperature patches remained unoccupied by individuals with the allele operating plastically after exposure to warm temperatures. Using complete habitat avoidance above the stressful temperature threshold, habitat selection reduced the overall population size due to the opportunity cost of avoiding areas with increased, but not guaranteed, mortality. Inclusion of plasticity within CDMetaPOP will provide the potential for genetic or plastic traits and 'rescue' to affect eco-evolutionary dynamics for research questions and conservation applications.


Inhibitory control in typically developing preschoolers: Relations among temperament, respiratory sinus arrhythmia, and behavior at age 4.
Although inhibitory control (IC) is associated with children's positive adjustment, we know relatively little about factors underlying its development. We examined whether baseline and on-task respiratory sinus arrhythmia [(RSA); a physiological measure of self-regulation] and private speech (a behavioral measure of self-regulation) interacted to confer differences on directly observed IC in 52 typically developing 4-year olds. We found that baseline RSA moderated the association between private speech and IC, such that private speech positively predicted IC in children with relatively higher baseline RSA, but was unrelated to IC in children with relatively lower RSA. We also found that children with a concordant physiological-behavioral pattern (i.e., high RSA and high private speech; low RSA and low private speech) had higher IC, higher effortful control, and lower negative emotionality than those with a discordant physiological-behavioral pattern (i.e., high RSA and low private speech; low RSA and high private speech). Individual differences in physiological and behavioral self-regulation indices may represent distinct regulation pathways that interact to confer differences in IC during the preschool years.


Imitation explains the propagation, not the stability of animal culture.
For acquired behaviour to count as cultural, two conditions must be met: it must propagate in a social group, and it must remain stable across generations in the process of propagation. It is commonly assumed that imitation is the mechanism that explains both the spread of animal culture and its stability. We review the literature on transmission chain studies in chimpanzees (Pan troglodytes) and other animals, and we use a formal model to argue that imitation, which may well play a major role in the propagation of animal culture, cannot be considered faithful enough to explain its stability. We consider the contribution that other psychological and ecological factors might make to the stability of animal culture observed in the wild.


3.0 Tesla high spatial resolution contrast-enhanced magnetic resonance angiography (CE-MRA) of the pulmonary circulation: initial experience with a 32-channel phased array coil using a high relaxivity contrast agent.
To evaluate the technical feasibility of high spatial resolution contrast-enhanced magnetic resonance angiography (CE-MRA) with highly accelerated parallel acquisition at 3.0 T using a 32-channel phased array coil, and a high relaxivity contrast agent. Ten adult healthy volunteers (5 men, 5 women, aged 21-66 years) underwent high spatial resolution CE-MRA of the pulmonary circulation. Imaging was performed at 3 T using a 32-channel phase array coil. After intravenous injection of 1 mL of gadobenate dimeglumine (Gd-BOPTA) at 1.5 mL/s, a timing bolus was used to measure the transit time from the arm vein to the main pulmonary artery. Subsequently following intravenous injection of 0.1 mmol/kg of Gd-BOPTA at the same rate, isotropic high spatial resolution data sets (1 x 1 x 1 mm3) CE-MRA of the entire pulmonary circulation were acquired using a fast gradient-recalled echo sequence (TR/TE 3/1.2 milliseconds, FA 18 degrees) and highly accelerated parallel acquisition (GRAPPA x 6) during a 20-second breath hold. The presence of artifact, noise, and image quality of the pulmonary arterial segments were evaluated independently by 2 radiologists. Phantom measurements were performed to assess the signal-to-noise ratio (SNR). Statistical analysis of data was performed by using Wilcoxon rank sum test and 2-sample Student t test. The interobserver variability was tested by kappa coefficient. All studies were of diagnostic quality as determined by both observers. The pulmonary arteries were routinely identified up to fifth-order branches, with definition in the diagnostic range and excellent interobserver agreement (kappa = 0.84, 95% confidence interval 0.77-0.90). Phantom measurements showed significantly lower SNR (P < 0.01) using GRAPPA (17.3 +/- 18.8) compared with measurements without parallel acquisition (58 +/- 49.4). The described 3 T CE-MRA protocol in addition to high T1 relaxivity of Gd-BOPTA provides sufficient SNR to support highly accelerated parallel acquisition (GRAPPA x 6), resulting in acquisition of isotopic (1 x 1 x 1 mm3) voxels over the entire pulmonary circulation in 20 seconds.


Incorporating physics to overcome data scarcity in predictive modeling of protein function: A case study of BK channels.
Machine learning has played transformative roles in numerous chemical and biophysical problems such as protein folding where large amount of data exists. Nonetheless, many important problems remain challenging for data-driven machine learning approaches due to the limitation of data scarcity. One approach to overcome data scarcity is to incorporate physical principles such as through molecular modeling and simulation. Here, we focus on the big potassium (BK) channels that play important roles in cardiovascular and neural systems. Many mutants of BK channel are associated with various neurological and cardiovascular diseases, but the molecular effects are unknown. The voltage gating properties of BK channels have been characterized for 473 site-specific mutations experimentally over the last three decades; yet, these functional data by themselves remain far too sparse to derive a predictive model of BK channel voltage gating. Using physics-based modeling, we quantify the energetic effects of all single mutations on both open and closed states of the channel. Together with dynamic properties derived from atomistic simulations, these physical descriptors allow the training of random forest models that could reproduce unseen experimentally measured shifts in gating voltage, ∆V1/2, with a RMSE ~ 32 mV and correlation coefficient of R ~ 0.7. Importantly, the model appears capable of uncovering nontrivial physical principles underlying the gating of the channel, including a central role of hydrophobic gating. The model was further evaluated using four novel mutations of L235 and V236 on the S5 helix, mutations of which are predicted to have opposing effects on V1/2 and suggest a key role of S5 in mediating voltage sensor-pore coupling. The measured ∆V1/2 agree quantitatively with prediction for all four mutations, with a high correlation of R = 0.92 and RMSE = 18 mV. Therefore, the model can capture nontrivial voltage gating properties in regions where few mutations are known. The success of predictive modeling of BK voltage gating demonstrates the potential of combining physics and statistical learning for overcoming data scarcity in nontrivial protein function prediction.


Prevalence of anxiety and post-traumatic stress (PTS) among the parents of babies admitted to neonatal units: A systematic review and meta-analysis.
Parents of babies admitted to neonatal units (NNU) are exposed to a range of potentially distressing experiences, which can lead to mental health symptoms such as increased anxiety and post-traumatic stress (PTS). This review aimed to describe how anxiety and PTS are defined and assessed, and to estimate anxiety and PTS prevalence among parents of babies admitted to NNU. Medline, Embase, PsychoINFO, Cumulative Index to Nursing and Allied Health literature were searched to identify studies published prior to April 14, 2021. Included studies were assessed using Hoy risk of bias tool. A random-effects model was used to estimate pooled prevalence with 95% CIs. Potential sources of variation were investigated using subgroup analyses and meta-regression. The review is registered with PROSPERO (CRD42020162935). Fifty six studies involving 6,036 parents met the review criteria; 21 studies assessed anxiety, 35 assessed PTS, and 8 assessed both. The pooled prevalence of anxiety was 41.9% (95%CI:30.9, 53.0) and the pooled prevalence of PTS was 39.9% (95%CI:30.8, 48.9) among parents up to one month after the birth. Anxiety prevalence decreased to 26.3% (95%CI:10.1, 42.5) and PTS prevalence to 24.5% (95%CI:17.4, 31.6) between one month and one year after birth. More than one year after birth PTS prevalence remained high 27.1% (95%CI:20.7, 33.6). Data on anxiety at this time point were limited. There was high heterogeneity between studies and some evidence from subgroup and meta-regression analyses that study characteristics contributed to the variation in prevalence estimates. The prevalence of anxiety and PTS was high among parents of babies admitted to NNU. The rates declined over time, although they remained higher than population prevalence estimates for women in the perinatal period. Implementing routine screening would enable early diagnosis and effective intervention. This research is funded by the National Institute for Health Research (NIHR) Policy Research Programme, conducted through the Policy Research Unit in Maternal and Neonatal Health and Care, PR-PRU-1217-21202. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care.


Dynamics of African swine fever virus (ASFV) infection in domestic pigs infected with virulent, moderate virulent and attenuated genotype II ASFV European isolates.
This study aimed to compare the infection dynamics of three genotype II African swine fever viruses (ASFV) circulating in Europe. Eighteen domestic pigs divided into three groups were infected intramuscularly or by direct contact with two haemadsorbent ASFVs (HAD) from Poland (Pol16/DP/ OUT21) and Estonia (Est16/WB/Viru8), and with the Latvian non-HAD ASFV (Lv17/WB/Rie1). Parameters, such as symptoms, pathogenicity, and distribution of the virus in tissues, humoral immune response, and dissemination of the virus by blood, oropharyngeal and rectal routes, were investigated. The Polish ASFV caused a case of rapidly developing fatal acute disease, while the Estonian ASFV caused acute to sub-acute infections and two animals survived. In contrast, animals infected with the ASFV from Latvia developed a more subtle, mild, or even subclinical disease. Oral excretion was sporadic or even absent in the attenuated group, whereas in animals that developed an acute or sub-acute form of ASF, oral excretion began at the same time the ASFV was detected in the blood, or even 3 days earlier, and persisted up to 22 days. Regardless of virulence, blood was the main route of transmission of ASFV and infectious virus was isolated from persistently infected animals for at least 19 days in the attenuated group and up to 44 days in the group of moderate virulence. Rectal excretion was limited to the acute phase of infection. In terms of diagnostics, the ASFV genome was detected in contact pigs from oropharyngeal samples earlier than in blood, independently of virulence. Together with blood, both samples could allow to detect ASFV infection for a longer period. The results presented here provide quantitative data on the spread and excretion of ASFV strains of different virulence among domestic pigs that can help to better focus surveillance activities and, thus, increase the ability to detect ASF introductions earlier.


A functional screen for the type III (Hrp) secretome of the plant pathogen Pseudomonas syringae.
Type III secreted "effector" proteins of bacterial pathogens play central roles in virulence, yet are notoriously difficult to identify. We used an in vivo genetic screen to identify 13 effectors secreted by the type III apparatus (called Hrp, for "hypersensitive response and pathogenicity") of the plant pathogen Pseudomonas syringae. Although sharing little overall homology, the amino-terminal regions of these effectors had strikingly similar amino acid compositions. This feature facilitated the bioinformatic prediction of 38 P. syringae effectors, including 15 previously unknown proteins. The secretion of two of these putative effectors was shown to be type III--dependent. Effectors showed high interstrain variation, supporting a role for some effectors in adaptation to different hosts.


Inhalant abuse.
Inhalant abuse - also known as volatile substance abuse, solvent abuse, sniffing, huffing and bagging - is the deliberate inhalation of a volatile substance to achieve an altered mental state. Inhalant abuse is a worldwide problem that is especially common in individuals from minority and marginalized populations, and is strongly correlated with the social determinants of health. It often affects younger children, compared with other forms of substance abuse, and crosses social and ethnic boundaries. Inhalants are pharmacologically diverse products that are selected for their low price, legal and widespread availability, and ability to rapidly induce euphoria. Chronic abuse is associated with serious and often irreversible effects. Widespread screening and early referrals to treatment programs have resulted in significant improvements in the mental, physical and social conditions of those affected. The present statement reviews critical aspects of inhalant abuse, highlighting new information and data that pertain to Aboriginal children and youth, and provides recommendations for treatment and prevention.


Polymorphisms of the reg1α gene and early onset type 2 diabetes in the korean population.
The Reg gene has been reported to be expressed in regenerating islets and Reg1 protein to be up-regulated at an early stage of diabetes in mice. As human Reg1α is homologous with murine Reg1, we investigated whether common variants in Reg1α are associated with type 2 diabetes in the Korean population. We sequenced the Reg1α gene to identify common polymorphisms using 24 Korean DNA samples. Of 11 polymorphisms found, five common ones (g.-385T>C [rs10165462], g.-36T>G [rs25689789], g.209G>T [rs2070707], g.1385C>G [novel], and g.2199G>A [novel]) were genotyped in 752 type 2 diabetic patients and 642 non-diabetic subjects. No polymorphism was associated with the risk of type 2 diabetes. However, g.-385C and g.2199A lowered the risk of early-onset type 2 diabetes, defined as a diagnosis in subjects whose age at diagnosis was 25 years or more but less than 40 years (odds ratio [OR], 0.721 [0.535 to 0.971] and 0.731 [0.546 to 0.977] for g.-385C and g.2199A, respectively) and g.1385G increased the risk of early-onset diabetes (OR, 1.398 [1.055 to 1.854]). Although adjusting for errors in multiple hypotheses-testing showed no statistically significant association between the three individual polymorphisms and early-onset diabetes, the haplotype H1, composed of g.-385C, g.1385C, and g.2199A, was associated with a reduced risk of early-onset diabetes (OR, 0.590 [0.396 to 0.877], P = 0.009). Polymorphisms in the Reg1α were not found to be associated with overall susceptibility to type 2 diabetes, though some showed modest associations with early-onset type 2 diabetes in the Korean population.


Advances in diagnosis and management of hypokalemic and hyperkalemic emergencies.
With up to 56% of individuals taking diuretics likely to develop hypokalemia, and comorbid disease and many other types of medications having the potential to induce hyperkalemia, potassium abnormalities are some of the most commonly seen electrolyte abnormalities in the emergency department (ED). Unless recognized and treated appropriately, they can also be some of the most deadly. Symptoms accompanying potassium abnormalities are often vague, involving multiple organ systems. This evidence-based review discusses the etiology, differential diagnosis, and diagnostic studies for detecting hypokalemia and hyperkalemia, including managing laboratory errors that lead to factitious potassium findings. Recognition and treatment of life-threatening dysrhythmias in hypokalemia and hyperkalemia are key to managing these potassium abnormalities. Electrocardiogram (ECG) findings, treatment algorithms, and controversies on treating potassium abnormalities in the ED are discussed, with recommendations on criteria for disposition.


[Neurochemical correlates of dominant behavior in mice].
The influence of genetic factors on the activity of a key catecholamine-synthesizing enzyme and the relationship between the synthesis parameters in catecholaminergic systems and the predisposition of male mice of inbred lines to dominate in a population were studied. It was determined that the interline variability of tyrosine hydroxylase activity in the cortex, hippocampus, hypothalamus, striatum, and hindbrain exceeded the intraline one. PT line and CBA/Lac males were characterized respectively by maximum and minimum enzymatic activity in the majority of brain regions and also by dominant and subordinate behavior determined by genotype. Significant rank interline correlations of noradrenaline levels in the striatum, hippocampus and hindbrain, tyrosine hydroxylase activity in the striatum and hindbrain, and the percentage of dominant males among the examined genotypes were found. It was concluded that a genetically determined relationship exists between biosynthetic processes in the noradrenergic neurons of the brain and a dominant behavior phenotype.


Halogenated cytisine derivatives as agonists at human neuronal nicotinic acetylcholine receptor subtypes.
Cytisine (cy) is a potent and competitive partial agonist at alpha4 subunit-containing nicotinic acetylcholine (nACh) receptors while at homomeric alpha7-nACh receptors it behaves as a full agonist with a relatively lower potency. In the present study, we assessed the effects of bromination or iodination of the pyridone ring of cy and N-methylcytisine (N-Me-cy) on the effects of these compounds on recombinant human (h) alpha7, halpha4beta2 and halpha4beta4 nACh receptors expressed in clonal cell lines and Xenopus oocytes. Halogenation at C(3) of cy or N-Me-cy usually brings about a marked increase in both affinity and efficacy at halpha7, halpha4beta2 and halpha4beta4 nACh, the extent of which depends on whether the halogen is bromine or iodine, and upon receptor subtype. The effects of halogenation at C(5) are strongly influenced by the specific halogen substituent so that bromination causes a decrease in both affinity and efficacy while iodination decreases affinity but its effects on efficacy range from a decrease (halpha7, halpha4beta4 nACh receptors) to a marked increase (halpha4beta2 nACh receptors). Based on these findings, which differ from those showing that neither the affinity nor efficacy of nicotine, 3-(2-azetidinylmethoxy)-pyridine or epibatidine are greatly affected by halogenation, dehalogenation or halogen exchange at equivalent positions, we suggest that cy, N-Me-cy and their halo-isosteres bind to neuronal nACh receptors in a different orientation allowing the halogen atom to interact with a hydrophobic halogen-accepting region within the predominantly hydrophobic agonist-binding pocket of the receptors.


Expression of an enzymically active glycosylphosphatidylinositol-anchored form of neutral endopeptidase (EC 22.214.171.124) in Cos-1 cells.
Neutral endopeptidase (EC 220.127.116.11, NEP) is a type-II integral membrane protein found in a wide variety of cell types. We previously produced a secreted form of the enzyme by deletion of the cytoplasmic and transmembrane domains and in-frame fusion of the cleavable signal peptide of pro-opiomelanocortin [Lemay, Waksman, Roques, Crine and Boileau (1989) J. Biol. Chem. 264, 15620-15623]. Here we have used this secreted form of NEP and fused to it the glycosylphosphatidylinositol (GPI)-anchor attachment signal of decay-accelerating factor to produce a GPI-anchored form. Expression of this chimeric form in Cos-1 cells resulted in cell-surface activity. This activity could be released from the cell surface by phosphatidylinositol-specific phospholipase C and radiolabelling studies showed that the protein could incorporate [3H]ethanolamine, indicating that the enzyme was GPI-anchored. The Km value, using [D-Ala2,Leu5]enkephalin as substrate, of GPI-anchored NEP (62 +/- 5 microM) was comparable with that of wild-type NEP (70 +/- 4 microM), as were the sensitivities to the inhibitors phosphoramidon and thiorphan. However, pulse-chase studies showed that the biosynthesis and cell-surface delivery of GPI-anchored NEP was delayed compared with that of the wild-type transmembrane form of NEP. These results suggest a lower rate of biosynthesis and/or cellular transport for GPI-anchored NEP compared with its transmembrane counterpart.


A fluorescent probe based on reversible Michael addition-elimination reaction for the cycle between cysteine and H2O2.
Cysteine oxidation by H2O2, generating either cysteine sulfenic acid (CSOH) or disulfide (CSSC), is involved in redox homeostasis and signaling. Compared with quantification of the cysteine content, monitoring the cysteine dynamics in real-time, in particular, takes on even greater importance. However, existing fluorescent probes suffer from low specificity or irreversible recognition mechanisms. In the present work, we have successfully developed a reversible fluorescent probe for the cycle between cysteine and H2O2 based on the Michael addition-elimination reaction. This probe features a specific and quantitative response to cysteine. The reversible detection was realized repeatedly with the addition of cysteine and H2O2 in order. We also demonstrated its usage for monitoring exogenous and endogenous cysteine in living cells. Eventually, this probe was capable of imaging cysteine dynamically in real-time.


[Changes in cerebrospinal fluid lactate and pyruvate levels during brain surgery under fluotane anesthesia].
The lactate and pyruvate content in the arterial blood and CSF of 24 patients operated on the brain under fluothane anesthesia with artificial ventilation of the lungs was measured. Towards the end of the operation and anesthesia a sizably elevated lactate level and accumulation of its excess in the blood were noted, these shifts having been more marked with hypocapnic ventilation of the lungs. An increased concentration of lactate and pyruvate in the cerebrospinal fluid was not attended by accumulation of lactate excess.


Necrotizing Fasciitis Secondary to a Primary Suture for Anoperineal Trauma by Motorcycle Accident in a Healthy Adult.
A 41-year-old man experienced a swollen scrotum three days after a motorcycle accident and presented to our hospital. He had had a primary suture repair for anoperineal trauma in an outside hospital at the time of the injury. He presented to us with general fatigue, low grade fevers, and perineal pain. Abdominal computed tomography showed subcutaneous emphysema from the scrotum to the left chest. The sutured wound had foul-smelling discharge and white exudate. We made the diagnosis of necrotizing fasciitis and immediately opened the sutured wound and performed initial debridement and lavage with copious irrigation. We continued antibiotics and lavage of the wound until the infection was controlled. Fortunately, the necrotizing fasciitis did not worsen and he was discharged after 15 days. Our experience indicates that anoperineal injuries should not be closed without careful and intensive follow-up due to the potential of developing necrotizing fasciitis.


Differential effects of clorgyline on sensitization to quinpirole in rats tested in small and large environments.
Cotreatment with clorgyline shifts the development of sensitization to the D2/D3 dopamine receptor agonist quinpirole from locomotion to mouthing, an effect apparently unrelated to the monoamine oxidase inhibition property of clorgyline. This phenomenon was demonstrated in rats examined in small activity chambers. However, like with other psychostimulant drugs, sensitization to quinpirole is modulated by environmental context. It is not known whether the clorgyline cotreatment effect is likewise influenced by the environment. To determine the generality of the clorgyline effect on behavioral sensitization by evaluating the effects of clorgyline cotreatment on sensitization to quinpirole in two different environments: a small activity chamber and a large open field. Male rats received eight injections of quinpirole (0.5 mg/kg, twice weekly) in an open field or activity chamber; one group in each environment received a constant infusion of clorgyline (1 mg/kg/day via osmotic minipumps) while the other group served as the sham surgery control. For quinpirole injection 7 or 8, rats were tested in the alternate environment. In activity chambers, clorgyline cotreatment switched sensitization to quinpirole from locomotion to mouthing. In the open field, clorgyline cotreatment increased mouthing and expanded the explored space without a change in path stereotypy or the amount of locomotion compared to treatment with quinpirole alone. Structure of the environment can modulate the clorgyline cotreatment effect on behavioral sensitization to quinpirole. The behavioral profiles produced by clorgyline cotreatment in the two environments resembled the behavioral effects observed with quinpirole and D1 agonist cotreatment. It is suggested that clorgyline cotreatment produces a behavioral profile characteristic of enhanced dopamine D1 and D2 receptor costimulation.


Comparison of different lipid substrates on intestinal adaptation in the rat.
The relative effects of medium chain (MCT) and long chain triglycerides (LCT) on intestinal morphology and functions were compared. Adult rats received intragastrically for 10 days an isoenergetic mixture containing either 50% MCT/50% LCT or 100% LCT. The other constituents of the diets were identical, and animals fed a standard diet orally were used as a reference group. Animals who were given the MCT/LCT diet showed a higher mucosal mass and protein content and increased villus length and crypt depth in the proximal part of the small intestine compared with the LCT and control diet groups. Administration of [3H] thymidine 12 hours before death resulted in a significant increase in the incorporation of the precursor into cellular DNA in the jejunum of rats given MCT. In rats given LCT as the only fat, the free fatty acid content of the microvillus membrane showed a 20 fold increase and at the same time there was a significant drop in the cholesterol content and in the cholesterol/protein ratio. Differences in the lipid composition of enterol diet or in the microvillus membrane did not effect adversely membrane bound hydrolase activities. These findings suggest that MCT in the diet confers advantages in addition to the provision of rapidly available energy.


Applications of Artificial Intelligence and Deep Learning in Glaucoma.
Diagnosis and detection of progression of glaucoma remains challenging. Artificial intelligence-based tools have the potential to improve and standardize the assessment of glaucoma but development of these algorithms is difficult given the multimodal and variable nature of the diagnosis. Currently, most algorithms are focused on a single imaging modality, specifically screening and diagnosis based on fundus photos or optical coherence tomography images. Use of anterior segment optical coherence tomography and goniophotographs is limited. The majority of algorithms designed for disease progression prediction are based on visual fields. No studies in our literature search assessed the use of artificial intelligence for treatment response prediction and no studies conducted prospective testing of their algorithms. Additional challenges to the development of artificial intelligence-based tools include scarcity of data and a lack of consensus in diagnostic criteria. Although research in the use of artificial intelligence for glaucoma is promising, additional work is needed to develop clinically usable tools.


Expression of lymphomagenic oncogenes in T-cell lymphomas of HPV 16 transgenic mice.
We have previously established that a dimer repeat of the complete HPV 16 genome is sufficient to cause multiple organ malignancies, either carcinomas or T-cell lymphomas, in transgenic mice. Here, we report the expression of oncogenes supporting the notion that these tumors arose via multiple oncogenic pathways. In these mice, the transgenic HPV 16 genome cosegregated with the tumor phenotype. E6/E7 expression was observed in both carcinomas and T-cell lymphomas, while E2 expression was observed only in T-cell lymphomas. Some of the T-cell lymphomas revealed E2 expression alone, implying that oncogenic pathways of HPV other than the one involving E6/E7 existed in these transgenic mice. To establish that this is the case, expression of genes downstream from E6/E7 and oncogenes involved in T-cell lymphoma formation were analyzed. p53 mutations were observed in two of five tumors that lacked E6 expression. High levels of c-myc gene expression were observed in five of six tumors with E7 expression, suggesting that a pathway involving E7, inactivation of Rb, and activation of c-myc is important in tumorigenesis of HPV 16 in these transgenic animals. High levels of expression of the c-Pim gene were also noted in two of three c-myc-expressing T-cell lymphomas, suggesting cooperation between these two proto-oncogenes. Activation of Hox-11, Tal2/SCL-2, and Rbtn1/Ttg1 expression, which are highly associated with human T-cell acute lymphoblastic leukemia (T-ALL), was observed in three of three T-cell lymphomas with E2 expression but not E6/E7 expression, showing that pathways to tumor formation not involving E6/E7 exist in these transgenic animals. At least two oncogenic pathways to tumors in HPV 16 transgenic mice exist, one involving E6/E7 and c-myc and the other involving E2 and lymphomagenic oncogenes.


Staff and patient feedback in mental health services for older people.
To compare the views of patients and staff on the quality of care provided on a psychogeriatric assessment ward over a five year period. To describe the quality improvements which were made as a result of their respective comments. Structured interviews were conducted with both patients and staff to obtain qualitative feedback and suggestions for improvement. An analysis of the percentage of positive and negative comments made by both patients and staff was used to compare the levels of satisfaction on a variety of aspects of the service provided. Psychogeriatric inpatient assessment ward. 75 patients and 85 staff interviews were conducted. Structured interviews covering various aspects of service quality. Staff and patients picked up on different aspects of service quality as important. Quality improvements which arose from the interviews were clearly different. Generally patients were more positive about the physical environment and standards of professional care than staff, but less positive about issues of privacy, social interaction, and empowerment. The perspectives of patients and staff in this area are not interchangeable. Both series of interviews led to several positive changes in the quality of care. Interviews with staff seem to have been valuable in a low morale situation. A structured interview format provided patients with an opportunity to feedback openly and led to changes in service quality which would not otherwise have occurred.


Meat mutagens and risk of distal colon adenoma in a cohort of U.S. men.
Cooking meats at high temperatures and for long duration produces heterocyclic amines and other mutagens. These meat-derived mutagenic compounds have been hypothesized to increase risk of colorectal neoplasia, but prospective data are unavailable. We examined the association between intakes of the heterocyclic amines 2-amino-3,8-dimethylimidazo[4,5,-f]quinoxaline (MeIQx), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-3,4,8-trimethylimidazo[4,5,-f]quinoxaline (DiMeIQx), and meat-derived mutagenicity (MDM) and risk of distal colon adenoma using a cooking method questionnaire administered in 1996 in the Health Professionals Follow-up Study cohort. Between 1996 and 2002, 581 distal colon adenoma cases were identified. Higher intake of MDM was marginally associated with increased risk of distal adenoma [fourth versus lowest quintile: odds ratio (OR), 1.39; 95% confidence interval (95% CI), 1.05-1.84; highest versus lowest quintile: OR, 1.29; 95% CI, 0.97-1.72; P(trend) = 0.08]. Adjusting for total red meat or processed meat intake did not explain those associations. Our data also suggested a positive association between higher MeIQx (highest versus lowest quintile: OR, 1.28; 95% CI, 0.95-1.71; P(trend) = 0.22) and risk of adenoma, but this association was attenuated after adjusting for processed meat intake. DiMeIQx and PhIP did not seem to be associated with risk of adenoma. In conclusion, higher consumption of mutagens from meats cooked at higher temperature and longer duration may be associated with higher risk of distal colon adenoma independent of overall meat intake. Because mutagens other than heterocyclic amines also contribute to MDM, our results suggest that mutagens other than heterocyclic amines in cooked meats may also play a role in increasing the risk of distal adenoma.


Use of Cold Plasma To Inactivate Escherichia coli and Physicochemical Evaluation in Pumpkin Puree.
This work aimed to study the pumpkin puree processing by cold plasma corona discharge as an alternative to heat treatment to reduce Escherichia coli contamination and evaluate physicochemical alterations, using argon (Ar) as the process gas. The treatment time to verify E. coli inactivation was between 2 and 20 min, while physicochemical alterations were analyzed at 5, 10, 15, and 20 min. Cold plasma corona discharge technology to inactivate E. coli proved to be promising, reaching 3.62 log cycles of reduction at 20 min of treatment. The inactivation kinectics showed a tendency of higher decrease with time. Physicochemical characteristics indicate that plasma induces a decrease of pH; however, there is an indication that process gases have an important role and react with the environment and procedure reactive species. This technology may reduce the total carotenoid content of pumpkin puree and in color, mainly the a* parameter, which showed great reduction.


Multifunctional Nanofibrous Scaffolds Capable of Localized Delivery of Theranostic Nanoparticles for Postoperative Cancer Management.
Postoperative recovery of cancer patients can be affected by complications, such as tissue dysfunction or disability caused by tissue resection, and also cancer recurrence resulting from residual cancer cells. Despite impressive progress made for tissue engineering scaffolds that assist tissue regeneration for postoperative cancer patients, the majority of existing tissue engineering scaffolds still lack functions for monitoring and killing residual cancer cells, if there are any, upon their detection. In this study, multifunctional scaffolds that comprise biodegradable nanofibers and core-shell structured microspheres encapsulated with theranostic nanoparticles (NPs) are developed. The multifunctional scaffolds possess an extracellular matrix-like nanofibrous architecture and soft tissue-like mechanical properties, making them excellent tissue engineering patch candidates for assisting in the repair and regeneration of tissues at the cancerous sites after surgery. Furthermore, they are capable of localized delivery of theranostic NPs upon quick degradation of core-shell structured microspheres that contain theranostic NPs. Leveraging on folic acid-mediated ligand-receptor binding, surface-enhanced Raman scattering activity, and near-infrared-responsive photothermal effect of the theranostic gold NPs (AuNPs) delivered locally, the multifunctional scaffolds display excellent active targeting, diagnosis, and photothermal therapy functions for cancer cells, showing great promise for adaptive postoperative cancer management.


The effect of exercising in different environments on heart rate and power output among older adults-a randomized crossover study.
A growing body of evidence suggests that exposure to nature is beneficial for human health. However, the observed health effect of nature may be mediated by physical activity and that humans are physically active at a higher intensity outdoors compared to when they are physical active indoors. This study examines the variation of heart rate and power output for a fixed rating of perceived exertion in a group of healthy older adults in three different environments representing three levels of exposure to nature. To this randomized, 3-by-3 crossover design study, healthy older adults (≥65 years) were recruited from local gyms. All participants participated in three experimental conditions; indoors, simulated outdoors and outdoor environments, in a randomized order. The participants exercised for 20 minutes at an intensity equivalent to a rating of 11-13 on the Borg scale for perceived exertion (RPE). Measurements of heart rate, power output (Watt) and ratings of perceived exertion were taken at minutes 1 to 6 and at minute 20. To examine the effect of the environment on heart rate and power, linear mixed models were used. In all, 48 participants (56% females) were included in the analysis. No significant main effects on the outcomes were observed for power output (p = 0.073, η2 = 0.04) or heart rate (p = 0.067, η2 = 0.04). No significant effect on the outcomes was observed. However, borderline significant outcomes for power output or heart rate outdoors in nature, along with previous studies in the field, indicates that such an effect cannot be completely ruled out, but any effect is likely to be small. Future research examining health benefits of the independent exposure to nature are encouraged to adjust for the dose of physical activity. ID: ISRCTN22230544.


Circ_0003146 upregulates SCARB1 expression by acting as a miR-1272 sponge to promote malignant behaviors of clear cell renal cell carcinoma.
Circular RNAs (circRNAs) exhibit essential regulation in the malignant development of clear cell renal cell carcinoma (ccRCC). The aims of this study were to investigate the role and mechanism of circ_0003146 in the biologic behaviors of ccRCC. RNA level analysis was performed through reverse transcription-quantitative PCR assay. Cell proliferation was measured by EdU assay and cell counting kit-8 assay. The protein expression was analyzed using a western blot. Flow cytometry and caspase 3 activity assay were used to assess cell apoptosis. Cell migration and invasion were evaluated via wound healing assay and transwell assay. Circ_0003146 function in vivo was determined by xenograft tumor assay. Dual-luciferase reporter assay was applied for target relation analysis. Circ_0003146 upregulation was detected in ccRCC tissues and cells. Downregulation of circ_0003146 induced inhibition of proliferation, migration, invasion and EMT but the promotion of apoptosis in ccRCC cells. Tumor growth in vivo was inhibited after knockdown of circ_0003146. Circ_0003146 directly interacted with miR-1272, and the miR-1272 sponging effect was responsible for the function of circ_0003146. Scavenger receptor class B type 1 (SCARB1) was a target of miR-1272, and circ_0003146 regulated SCARB1 level by absorbing miR-1272. The regulation of circ_0003146 in ccRCC progression was achieved by upregulating SCARB1 in part. The current findings demonstrated that circ_0003146 contributed to the malignant progression of ccRCC via inducing SCARB1 upregulation by targeting miR-1272.


Phase-sensitive frequency conversion of quadrature modulated signals.
Two mechanisms that can make frequency conversion based on nonlinear mixing dependent on the phase of the input signal are identified. A novel phase-to-polarization converter that converts the orthogonal phase components of an input signal to two orthogonally polarized outputs is proposed. The operation of this scheme and a previously reported scheme at an increased symbol rate are simulated with semiconductor optical amplifiers (SOAs) as the nonlinear devices. Experimental results demonstrate the effectiveness of SOAs for nonlinear mixing over a wide range of wavelengths and difference frequencies and confirm the accuracy of the numerical model.


Ticket to Ride: I-deals as a Strategic HR Tool for an Employable Work Force.
We describe how idiosyncratic deals (I-deals), in this case I-deals focused on workers' employability enhancement, can serve as a powerful strategic HR tool for simultaneously meeting both the strategic goals of employers and the career goals of employees. Building on a sustainable career perspective, I-deals are interpreted as highly valuable, as they can help individual employees to more easily adapt to the fast-changing environments that nowadays characterize society and the labor market. After theoretical outlines on the concepts of I-deals and employability, we argue that I-deals can form the basis for integrative employment relationships aimed at employability enhancement. This article concludes with concrete recommendations for practice, indicating that in order to enable the sound use of I-deals as a strategic HR tool, organizations should discuss I-deals and employability openly through constructive dialogue. Moreover, examples for achieving this through specific practices, such as working with employability coaches and world cafés on employability, are described.


Learning disabilities. Using hydrotherapy: maximising benefits.
People with a learning disability are increasingly using hydrotherapy for exercise, socialising, and the release of tension and energy. For those with a physical disability, it offers an opportunity for independent activity from which they may be precluded outside the hydrotherapy pool. The author discusses guidelines for staff involved in hydrotherapy sessions before examining in detail the benefits this form of treatment has to offer.


Rationalization of standards for medical devices-Part 1.
Current practices for preparing standards in general-and standards for medical devices, instruments, and products in particular-are too slow, too expensive, and too cumbersome. There is a need, therefore, for establishing administrative mechanisms to expedite standards preparation. This paper addresses some administrative, conceptual, and methodological aspects of standards preparation and suggests actions that might contribute to improvements in the effectiveness of standards and in the methods of their preparation.


The effect of altering the external calcium concentration and a calcium channel blocker, verapamil, on microvascular leaky sites and dextran clearance in the hamster cheek pouch.
The role of calcium in contractile mechanisms has been well documented. Since the formation of intraendothelial gaps may be due to a contractile process, these studies were initiated to describe the effects of altering the external calcium concentration and a calcium blocker, verapamil, on the development of leaky sites and clearance of dextran in the hamster cheek pouch under normal and histamine-stimulated conditions. Adult Syrian hamsters were anesthetized and tracheostomized, and the femoral vein was cannulated for injecting the FITC-Dextran-70K. In all hamsters, a removable plastic chamber was placed in the cheek pouch to observe and collect suffusate from the microvasculature. In one series of experiments, suffusion was begun with either "normal" calcium (1.5 mM) or a calcium-free, Ringer's bicarbonate (pH 7.4, 36 degrees) buffer. After a 30-min period, fluorescein-labeled dextran (FITC-Dextran-70K) was given intravenously and the number of leaky sites and dextran clearance determined for 30-45 min. Two 5-min periods of stimulation with histamine (10(-7) and 10(-6) M) followed by a 30-min equilibration were completed while the above measurements were repeated. Then, the suffusate was switched to the opposite calcium buffer and the same sequence repeated. A similar protocol was followed using either the "normal" buffer or a high (4.5 mM)-calcium buffer. In another series of experiments, similar measurements were completed with and without verapamil (10(-4) M) using a "normal" calcium buffer and histamine-stimulated conditions. In the control, nonstimulated state, there was a significant increase in the leaky sites while suffusing with low-calcium buffer; however, there were no changes in leaky sites while suffusing with the high-calcium buffer. In the histamine-stimulated state, the increase in the number of leaky sites and dextran clearance was attenuated with the low-calcium buffer and potentiated with the high-calcium buffer. While suffusing with the verapamil buffer, there was an increase in the control number of leaky sites and in the histamine-stimulated state there was an attenuation of the histamine-stimulated response. These results indicate that external calcium influences and modulates microvascular leaky sites in normal and stimulated states and that the formation of leaky sites and dextran clearance after histamine stimulation require the transmembrane flux of calcium. Also, the formation of leaky sites was coupled directly to the clearance of dextran.


African American women's coping with health care prejudice.
African American clients have reported racism and prejudice in health care; yet there is limited documentation of the strategies used to cope with these experiences. This study describes African American women's perceptions of prejudice in health care and the strategies used to cope with the experiences. This qualitative study used the constructivist perspective of interpretive interactionism for paradigmatic and methodological guidance. Participants were 20 women ranging from age 26 to 74 years with 50% having a high school education. Individual interviews consisting of five areas were conducted with three instruments measuring ethnic identity, socioeconomic status, and general demographics. The analyses provide two themes: experience with the "White health care system" and strategies for coping with the prejudice, which included getting angry, learning to unlearn, being assertive, and walking away. Consistent with the discussions of race in the United States, racism in health care has become a subtle entity that infuses health care relationships.


Identification of neural genes using Xenopus DNA microarrays.
To isolate novel genes regulating neural induction, we used a DNA microarray approach. As neural induction is thought to occur by means of the inhibition of bone morphogenetic protein (BMP) signaling, BMP signaling was inhibited in ectodermal cells by overexpression of a dominant-negative receptor. RNAs were isolated from control animal cap explants and from dominant-negative BMP receptor expressing animal caps and subjected to a microarray experiment using newly generated high-density Xenopus DNA microarray chips representing over 17,000 unigenes. We have identified 77 genes that are induced in animal caps after inhibition of BMP signaling, and all of these genes were subjected to whole-mount in situ hybridization analysis. Thirty-two genes showed specific expression in neural tissues. Of the 32, 14 genes have never been linked to neural induction. Two genes that are highly induced by BMP inhibition are inhibitors of Wnt signaling, suggesting that a key step in neural induction is to produce Wnt antagonists to promote anterior neural plate development. Our current analysis also proves that a microarray approach is useful in identifying novel candidate factors involved in neural induction and patterning.