Formation and use of poly-L-histidine-catalase complexes: protection of cells from hydrogen peroxide-mediated injury.
Insoluble complexes of poly-L-histidine (polyhistidine) and catalase were prepared by mixing the two reactants together in solution at pH 5.5 and subsequently elevating the pH to approximately 7.0, at which point they precipitated. Complexes formed at optimal ratios of polyhistidine to catalase contained essentially all of the catalase present in the original solution. The catalase present in such complexes contained greater than 50% of the H2O2-inhibiting activity of the native catalase used to prepare the complexes. The insoluble complexes rapidly bound to viable endothelial cells and were resistant to removal by extensive washing. The presence of polyhistidine-catalase complexes on the cell surface protected the cells against injury mediated by H2O2 or activated polymorphonuclear leukocytes. These data show that polyhistidine-catalase complexes can be prepared that have a high affinity for cells and that retain catalase activity. These complexes may be useful in treating inflammatory conditions in which it is necessary to maintain a high local concentration of inhibitor.


Oral isotretinoin in photoaging: objective histological evidence of efficacy and durability.
The off-label use of oral isotretinoin in photoaging is a therapeutic tool that has been used by dermatologists. There are few studies to corroborate its effectiveness and durability. To assess, both clinically and histologically, the changes caused by the use of oral isotretinoin in skin photoaging as well as the duration of the effects. 20 female patients, aged 45-50 years, with phototypes II-VI, none of whom had experienced menopause, were treated with 20mg oral isotretinoin, 3 days a week, for 12 weeks. They underwent clinical analysis and skin biopsies in the pre-auricular region, while histologic cuts enabled assessment of the solar elastosis level and morphologic analysis. Clinically, patients, as well as the researching and the assessor physicians, noticed improvement in skin quality. One patient presented severe solar elastosis, 11 manifested the moderate form, while 8 presented the discreet type. According to histological analysis, 65% of the patients revealed alteration in the distribution and thickness of the elastic fibers, which can be interpreted as a histological improvement, while 60% showed an increase in collagen density. We observed an increase in collagen density, from 51.2% to 57.4%, (p=0.004). At the end of the 12-week follow-up period, this density decreased to 54.7% (p=0.050). There was an increase in the density of elastic fibers, from 26.5% to 31.3%, (p=0.02), which had dropped to 27.5% at the end of the 12-week follow-up period. The study confirmed the role of oral isotretinoin in remodeling the extracellular matrix against photoaging, as well as its durability after 12 weeks, especially when we consider collagen fibers.


Warp-Speed Covid-19 Vaccine Development: Beneficiaries of Maturation in Biopharmaceutical Technologies and Public-Private Partnerships.
It is anticipated that effective vaccines will enable the resumption of social and economic normalcy. Current calls for masking, social distancing and other restrictive measures for the public-good are difficult to enforce and are unstainable. As ~2-4% of the 50 million SARS-CoV2-infected have succumbed to Covid-19, the US department of Health and Human Services has organized a public-private partnership called Operation Warp Speed (OWS) to develop, produce and deliver 300 million doses of safe and effective vaccines with a January 2021 target. While a majority of the 300+ Covid-19 vaccine candidates are in various stages of preclinical and early-stage clinical testing, 6 clinical candidates are supported with over 10 billion USD plus integrated resources under the OWS agenda. This unprecedented approach is investing in the manufacture of product candidates ahead of product approval. It is enabled by new gene and recombinant pharmaceutical platform technologies that are accelerating the clinical study timeline from ~10 to less than 1 year. It is anticipated that one or more of the 6 candidates under the OWS initiative will be safe, effective and provide a sustained immune response to prevent infection and disease progression. This way, social and economic activities could return to normalcy.


Hippocampal electrical activity following local tetanization. I. Afterdischarges.
Following a short (1-10 s) train of repetitive stimulation delivered to the hippocampal CA1 region, the following sequelae of afterdischarges (ADs) was seen: (1) a silent period of 2-4 s, (2) a large primary (1 degree) AD usually alvear-surface negative and deep positive, (3) a period of suppressed hippocampal EEG, (4) a secondary (2 degrees) hippocampal AD, and after 3-6 min, (5) 15-25 min of enhanced (up to 10 times normal) fast (30-70 Hz) waves. The 2 degrees hippocampal AD was preceded by or simultaneous with large AD at the amygdaloid electrodes. Electrolytic lesions (n = 7) or large heat lesions of the amygdala (n = 5) or electrolytic lesions of the medial septum (n = 10) were not successful in suppressing the 2 degrees hippocampal AD. However, 4 rats with radiofrequency lesion and 3 rats with bilateral aspiration lesion of the entorhinal cortex had diminished or no 2 degrees hippocampal AD. The fast waves after tetanization were reversed 180 degrees across surface and deep CA1 electrodes. The fast wave increase was blocked by atropine sulfate (25-50 mg/kg i.p.), scopolamine hydrochloride (5 mg/kg i.p.) and medial septal lesions. It was concluded that the 2 degrees hippocampal AD may depend on a reverberation of neural circuitry involving the entorhinal cortex. The 2 degrees AD recorded from amygdala electrodes may partly reflect spreading of activities from the entorhinal cortex. On the other hand, the increase in fast waves after tetanization requires an intact septohippocampal, muscarinic cholinergic input, and may depend on an enhanced cholinergic input or an increased response.


An Analysis of Xpert Test for Diagnosing Maxillofacial Tuberculosis.
Maxillofacial tuberculosis is a diagnostic challenge for surgeons. The aim of this study was to present a detailed analysis of Xpert test in diagnosing maxillofacial tuberculosis and to analyse the accuracy of Xpert test results for various tissues of maxillofacial region. In this cross-sectional study, patients were selected randomly from outpatient department. The patients who had clinical picture and differential diagnosis highly suggestive of maxillofacial tuberculosis were included. Patients were divided into three different groups depending upon the site of involvement. The samples collected from the patients were further subdivided depending upon the type of specimen. Patients were screened first by routine tests, and the negative cases were followed by Xpert test for tuberculosis. A total of 54 patients were enrolled in the study, 13 patients were found to be positive for maxillofacial tuberculosis on routine screening tests for tuberculosis, and 41 tested negative on routine test and were evaluated further through Xpert test. Specimens from bone (n12), soft tissue and skin biopsy (n15) and aspirates from lymph nodes (n14) were obtained and tested. Twenty-one samples were found to be positive, and 20 were negative upon Xpert testing. There was a statistically significant difference seen between the test groups (p < 0.01) with higher frequency of negative results in routine test. The p value for various specimens containing pus, biopsies and aspirates was 0.045, 0.023 and 0.067, respectively. Xpert test is more accurate when compared to routine test for diagnosing maxillofacial tuberculosis. Although accuracy of Xpert test is better for pus and biopsy samples in the specimens from bone and soft tissue, it gives poor accuracy for aspirated cells. The aspirates from lymph nodes were more susceptible for false negative test.


Application of an extracorporeal prefenestrated stent graft in endovascular repair of ascending aorta and aortic arch lesions.
Aortic dissection involving the ascending aorta and aortic arch is a serious condition. Treatment using traditional surgical methods has certain disadvantages. This study investigated the effectiveness of thoracic endovascular repair of aortic dissection using an external prefenestrated stent. We present a series of aortic dissection cases involving the ascending aorta and aortic arch treated with an external prefenestrated stent. Postoperative follow-up of the patients showed that all stents were released at the proper position and that branch vessels were not occluded, and there were no instances of type I endoleak. One patient died suddenly one week after surgery; another experienced retrograde type A aortic dissection in the second week; and type I endoleak occurred in one patient in the first week, although this resolved within six months. No serious complications such as cerebrovascular events, acute spinal cord ischemia, and paraplegia occurred during the perioperative period. All patients had false lumen thrombosis in the ascending aorta and aortic arch. Prefenestrated stent grafting is a feasible treatment option for repairing an entry tear in the ascending aorta.


The role of miRNA-223 in cancer: Function, diagnosis and therapy.
MicroRNAs (miRNAs) constitute a large family of small, non-coding RNAs with the capacity to regulate gene expression post-transcriptionally. miRNAs appear to hold promise of mechanistic explanations for various physiological and pathological processes. miRNA-223 is highly conserved and preferentially expressed in the hematopoietic system in regulation of myeloid differentiation. Recently, increasing evidence suggests that miRNA-223 may also play an essential part in both hematological malignancies and solid tumors. miRNA-223 can function as either an oncogene or a tumor suppressor gene, which is achieved by targeting a wide range of genes and regulating downstream signal transduction. As yet, the function of miR-223 in cancer has not been fully characterized and understood. To make it more clear, this review firstly summarizes the present understanding of the regulation of miR-223 at the molecular level, its crucial role in oncogenesis, development, and metastasis, its function as a diagnostic and prognostic biomarker and finally, its potential applications in monitoring and therapy of diverse types of malignancies.


Preservation of Neurovascular Coupling to Cognitive Activity in Anterior Cerebrovasculature During Incremental Ascent to High Altitude.
Background: High altitude sojourn challenges blood flow regulation in the brain, which may contribute to cognitive dysfunction. Neurovascular coupling (NVC) describes the ability to increase blood flow to working regions of the brain. Effects of high altitude on NVC in frontal regions undergoing cognitive activation are unclear but may be relevant to executive function in high-altitude hypoxia. This study sought to examine the effect of incremental ascent to very high altitude on NVC by measuring anterior cerebral artery (ACA) and middle cerebral artery (MCA) hemodynamic responses to sustained cognitive activity. Materials and Methods: Eight adults (23 ± 7 years, four female) underwent bilateral measurement of ACA and MCA mean velocity and pulsatility index (PI) through transcranial Doppler during a 3-minute Stroop task at 1400, 3440, and 4240 m. Results: Resting MCA and ACA PI decreased with high-altitude hypoxia (p < 0.05). Cognitive activity at all altitudes resulted in similar increases in MCA and ACA mean velocity, and decreases in ACA and MCA PI (p < 0.05 for MCA, p = 0.07 for ACA). No significant altitude-by-Stroop interactions were detected, indicating NVC was stable with increasing altitude. Conclusions: Ascent to very high altitude (4240 m) using an incremental profile that supports partial acclimatization does not appear to disturb (1) increases in cerebral blood velocity and (2) reductions in pulsatility that characterize optimal NVC in frontal regions of the brain during cognitive activity.


The importance of considering single testing when two tests are available.
When considering two dichotomous tests in combination for reaching a treatment decision, the choice between single and multiple testing depends, in part, on the pretest probability of disease. The authors show that two tests are never preferred to a single test for all disease probabilities, regardless of whether the two tests are performed in parallel or in series.


Prevention and treatment of cancer-associated thrombosis in France: A national survey among vascular disease and supportive care specialists.
Long-term use of low-molecular-weight heparins (LMWH) for the treatment of cancer-associated thrombosis (CAT) has been well-established. Conversely, the use of thromboprophylaxis in patients with cancer remains controversial in the absence of homogeneous guidelines. Our aim was to assess the awareness of treatment guidelines and the management of patients with CAT in daily clinical practice. A national survey based on an open questionnaire developed by a panel of health professionals including specialists in vascular medicine, oncology, supportive care and pharmacy, was proposed on line to 2104 specialists experts in the management of CAT with the objective to collect at least 400 answers. Clinical practice assessment included the treatment of lung adenocarcinoma-associated thrombosis, the use of thromboprophylaxis and factors influencing the management of patients with CAT. A total of 401 questionnaires were completed by specialists of vascular medicine (68%), oncology (12%) and other (20%). LMWH was the preferred option for over 90% of the participants for the treatment of recent overt proximal pulmonary embolism or deep-vein thrombosis. Up to 70% of the participants considered treatment duration for 6 months and more than 12 months in case of active malignancy. Patient management in the setting of incidental VTE and thromboprophylaxis were heterogeneous in the absence of clear guidance while VTE risk scores would be used by only 14% of participants. Patients with CAT are properly managed based on clear and consistent guidelines. Patient care is heterogeneous regarding treatment duration beyond 6 months and thromboprophylaxis while VTE risk scores are misused. Identification of referent health care professionals for CAT management and more clear guidelines are required.


Dependence of ricin toxoid vaccine efficacy on the structure of poly(lactide-co-glycolide) microparticle carriers.
Biodegradable microparticles made of poly(lactide-co-glycolide) (PLG) were used for protracted and pulsed-release of the incorporated ricin toxoid (RT) vaccine to reduce the multiple immunization doses and the time required to induce complete protection against lethal aerosol-borne ricin challenge. The release rate of RT encapsulated in PLG microparticles was controlled by polymer selection and varying the preparation procedures, which allowed us to control microparticle size and the distribution of the vaccine in the polymeric matrix. PLG-microparticles in which RT vaccine was distributed heterogeneously in small pockets stimulated a rapid antibody response which was independent of the polymeric composition of the carriers. PLG-microparticles in which RT vaccine was distributed homogeneously throughout the polymeric matrix induced a slower antibody response, which depended on the polymeric composition of the carriers. Administration of RT in homogeneous microparticles made from 50/50 PLG or 100% polylactide stimulated two distinct anti-ricin IgG peaks, while RT in heterogeneous microparticles stimulated identical IgG peaks. An early (3 weeks) and long-lasting (1 year or longer) anti-ricin antibody response was evoked by a single administration of encapsulated RT vaccine when prepared by the above-mentioned conditions. In contrast, three administrations of the aqueous RT were required to stimulate similar antibody response. Reduction of immunization time from 6 to 4 weeks was achieved with RT encapsulated in small homogeneous microparticles but not with homogeneous large microparticles. These results demonstrated the usefulness of biodegradable microparticles to improve the efficacy of immunization with RT vaccine and probably many other vaccines as well.


High-grade lumbosacral spondylolisthesis reduction and fusion in children using transsacral rod fixation.
There is no consensus on how to treat surgically high-dysplastic developmental spondylolisthesis in children and adolescents. Although reducing spinal deformity seems mandatory, the issue of surgical reduction versus in situ fusion remains controversial. The files of 12 consecutive patients surgically treated for a grade 3 or 4 spondylolisthesis were reviewed. The treatment consisted in L4 to sacrum reduction and fusion by posterior approach. The reduction of lumbopelvic imbalance was made intraoperatively using a trans-sacral rod fixation technique. Mean preoperative L5 anterior slippage was 72.3 % (60 to 95 %). The mean preoperative lumbosacral tilt angle was 70.5° (43 to 92°). Mean final lumbosacral tilt angle was 102° (91 to 114°). Mean final L5 anterior slippage was 19 % (7 to 63 %). Neurological complications (radicular L5 or S1 deficits) were noted in five patients. At final follow-up L4 to S1 fusion was achieved in all patients. No patient had persistent deficit or radicular pain. The fusion rate in our series proved to be optimal. Thanks to the trans-sacral rod fixation, lumbosacral kyphosis correction was very good. The intrasacral positioning of the screws reduces the risk of implant prominence especially in such pediatric patients. We stress the importance to avoid complete slip reduction in such patients to minimize stretching on L5 and S1 roots. No additional immobilization is needed due to solid posterior instrumentation. Doing such procedure only by posterior approach avoids anterior approach-related complications.


Clinical and economic impact of "triple therapy" for Helicobacter pylori eradication on peptic ulcer disease in Australia.
Helicobacter pylori infection has had a major impact on the global health of billions of people. Triple therapy was extensively used in Australia by 1986 for H pylori eradication after its discovery in 1984 and was critical in reducing the morbidity and mortality associated with this infection. This study analyzed hospital admission, mortality, and therapeutic data to determine the economic and clinical impact that antibiotic triple therapy had on peptic ulcer disease (PUD) in Australia. An analysis of indirect and direct cost-savings in Australia between 1990 and 2015 associated with triple therapy and the impact on PUD mortality and hospital admissions. The direct and indirect impacts of PUD treated by triple therapy between 1990 and 2015 suggest that triple therapy is likely to have prevented 18 665 deaths, and saved 258 887 life years and 33 776 productive life years. The total savings, over the 26-year period, including direct and indirect costs, are calculated to be $10.03 billion, equating to an average annual saving of $393.419 million. This study highlights the enormous benefits to Australia's health care of the discovery of triple therapy, a relatively low-cost antibiotic regimen which brought considerable savings via the reduction in morbidity (hospital admissions) and mortality related to PUD. It is likely that benefits of similar scale occurred internationally.


Computational evidence for hundreds of non-conserved plant microRNAs.
MicroRNAs (miRNA) are small (20-25 nt) non-coding RNA molecules that regulate gene expression through interaction with mRNA in plants and metazoans. A few hundred miRNAs are known or predicted, and most of those are evolutionarily conserved. In general plant miRNA are different from their animal counterpart: most plant miRNAs show near perfect complementarity to their targets. Exploiting this complementarity we have developed a method for identification plant miRNAs that does not rely on phylogenetic conservation. Using the presumed targets for the known miRNA as positive controls, we list and filter all segments of the genome of length approximately 20 that are complementary to a target mRNA-transcript. From the positive control we recover 41 (of 92 possible) of the already known miRNA-genes (representing 14 of 16 families) with only four false positives. Applying the procedure to find possible new miRNAs targeting any annotated mRNA, we predict of 592 new miRNA genes, many of which are not conserved in other plant genomes. A subset of our predicted miRNAs is additionally supported by having more than one target that are not homologues. These results indicate that it is possible to reliably predict miRNA-genes without using genome comparisons. Furthermore it suggests that the number of plant miRNAs have been underestimated and points to the existence of recently evolved miRNAs in Arabidopsis.


Karyotypic diversity of the armoured catfish genus Hypostomus (Siluriformes: Loricariidae) in the context of its occurrence and distribution.
This study taxonomically reviewed the specimens studied by Artoni & Bertollo (1996) and assimilated species of Hypostomus into three groups according to their cytogenetic characteristics, vagility and occurrence environments.


Femtosecond laser writing of near-surface waveguides for refractive-index sensing.
Femtosecond laser writing of optical waveguides and components in glasses has been a remarkably growing research field during the last two decades. However, such laser- inscribed optical components were mostly written within the volume of the glass due to the unavoidable ablation that arises when the focal spot is approaching the glass surface. This has generally limited the interaction of light with the surrounding medium thus preventing sensing functionality. In this paper, we present the inscription of surface and near-surface silver based waveguides in a silver containing glass with no need for additional processing as it is the case for standard type I waveguides. In addition, an ultra-sensitive refractive index sensor in a 1 cm glass chip is obtained based on near-surface waveguides interacting with liquid droplets acting as top-layer on the glass surface. Remarkably, the device exhibits a novel double-wing feature that sharpens the response and enhances its sensitivity. Our results highlight the advantages of silver based waveguides paving the way towards further surface based sensors in fibers.


Production, characterization and properties of polysaccharide depolymerizing enzymes from a strain of Curvularia inaequalis.
Xylanase, beta-glucosidase, beta-xylosidase, endoglucanase and polygalacturonase production from Curvularia inaequalis was carried out by means of solid-state and submerged fermentation using different carbon sources. beta-Glucosidase, beta-xylosidase, polygalacturonase and xylanase produced by the microorganisms were characterized. beta-Glucosidase presented optimum activity at pH 5.5 whereas xylanase, polygalacturonase and beta-xylosidase activities were optimal at pH 5.0. Maximal activity of beta-glucosidase was determined at 60 degrees C, beta-xylosidase at 70 degrees C, and polygalacturonase and xylanase at 55 degrees C. These enzymes were stable at acidic to neutral pH and at 40-45 degrees C. The crude enzyme solution was studied for the hydrolysis of agricultural residues.


Student Nurse Screening, Brief Intervention and Referral to Treatment Training Program: Analysis 2016-2019.
Screening, brief intervention and referral to treatment (SBIRT) is an evidence-based set of skills and strategies used by health care providers. Data have suggested SBIRT should be used in detecting persons at risk for substance use and be included in every primary care encounter, as many needing substance abuse treatment do not receive it. This descriptive study evaluated data for 361 undergraduate student nurses who participated in SBIRT training. Pretraining and 3-month posttraining surveys were used to evaluate changes in trainees' knowledge, attitudes, and skills toward people with substance use disorder. A satisfaction survey immediately after the training measured satisfaction with and usefulness of the training. Eighty-nine percent of students self-reported that the training increased their knowledge and skills related to screening and brief intervention. Ninety-three percent reported that they intended to use these skills in the future. Pre-post measures indicated statistically significant increases in knowledge, confidence, and perceived competence on all measures. Both formative and summative evaluation assisted in improving trainings each semester. These data confirm the need to integrate SBIRT content across the undergraduate nursing curriculum and include faculty and preceptors to improve rates of screening in clinical practice.


Multidrug-resistant Streptococcus pneumoniae causing invasive pneumococcal disease isolated from a paediatric patient.
The emergence of non-vaccine multidrug-resistant Streptococcus pneumoniae serotypes is on rise. This study was performed to investigate a highly resistant serotype 15A S. pneumoniae isolated from the blood specimen of a 20-month-old patient who died of her infection. The SS40_16 isolate was resistant to erythromycin, co-trimoxazole, tetracycline, and chloramphenicol, as well as to penicillin, ceftriaxone, and cefotaxime (using meningitis cut-off points, Clinical and Laboratory Standards Institute). The isolate belonged to sequence type 1591 (ST1591) and was related to CC81 clonal complex, suggesting the possibility of horizontal gene transfer. Scanning electron microscopy comparison between resistant and sensitive pneumococcal isolates also indicated similar phenotypic characteristics that confer high resistance. The emergence of highly resistant non-vaccine pneumococci is of great concern to public health and in the clinical setting. Pneumococcal surveillance programs represent a crucial tool, not only for determining the impact of pneumococcal conjugate vaccines, but also for monitoring the selective pressure of serotype replacement with regard to the treatment of invasive pneumococcal disease.


The nature of ion and water barrier crossings in a simulated ion channel.
Using a combination of techniques, including molecular dynamics, time-correlation analysis, stochastic dynamics, and fitting of continuum diffusion theory to electrophysiological data, a characterization is made of thermally driven sodium, water, and D2O motion within the gramicidin A channel. Since the channel contents are constrained to move in a single-file fashion, the motion that corresponds to experimentally measurable rates of permeation of the membrane is the motion of the center of mass of the channel contents. We therefore emphasize channel contents center-of-mass motion in our analysis of molecular dynamics computations. The usual free energy calculation techniques would be of questionable validity when applied to such motion. As an alternative to those techniques, we postulate a periodic sinusoidal free energy profile (related to the periodic structure of the helical channel) and deduce the fluid dynamic diffusion coefficient and the height and spacing of the free energy barriers from the form of the mean-square-deviation function, using stochastic computations. The fluid dynamic friction in each case appears similar to that for aqueous solution. However, the diffusive motions are modulated by a spatially periodic free energy profile with a periodicity characteristic of an L-D pair of amino acids in the gramicidin helix, approximately 1.7 A in the model we use. The barrier height depends on which substance is moving in the channel, but in each case is several times thermal energy. For barriers of this width and height, the motion is intermediate between the low-friction (transition-state) and high-friction (Brownian) limits. Thus, neither of these formalisms that have been used commonly to describe membrane permeation gives an accurate picture of the underlying physical process (although the Brownian description seems closer to correct). The non-Markovian Langevin equation must be solved to describe properly the statistics of the process. The "channel state of matter" characteristic of the channel contents appears to have some properties typical of the solid and some typical of the liquid state. The magnitude of the local friction and nature of the ion solvation are similar to the liquid state, but the periodicities of structure, free energy, and dynamics are somewhat solid-like. The alignment of water dipoles in the channel bears some resemblance to the orientational ordering of a nematic liquid crystal, but unlike a nematic liquid crystal, the waters have a degree of translational order as well. Thus, the "channel state" is not adequately described by analogy to either the solid or liquid states or to liquid crystals but must be dealt with as its own characteristic type of condensed matter.


Characterization of chemokine receptors.
This unit describes the procedures for measuring binding of a radiolabeled chemokine to chemokine receptors in cells or cell membranes. The whole-cell binding assay can be used for both purified leukocytes as well as transfected cell lines expressing chemokine receptors. Two basic protocols are described. The first is applicable to all cells expressing chemokine receptors, both primary cultures as well as recombinantly transfected cell lines expressing a single chemokine receptor. The second is used principally for transfected cell lines and measures chemokine binding to cell membranes using scintillation proximity assay (SPA) methodology, but does not require washing steps and thus is applicable to automated high-throughput screening strategies. An alternative procedure is also described which also uses SPA methodology to measure GTP-gamma-S binding to chemokine receptors in cell membranes. The two basic protocols can be used to determine the binding of compounds to chemokine receptors, while the alternate protocol determines the effects of compounds on the chemokine-stimulated activation of the receptor.


Dynamics of mirex and its principal photoproducts in a simulated marsh system.
Three simulated marsh systems were constructed, containing sediment, marsh plants, oysters, blue crabs, fiddler crabs, and two species of top minnows. Seawater entered each of the pools by flowing across a trough, two of which contained Mirex bait. Tidal fluctuations were simulated. Samples of water, bait, and animals were periodically analyzed. All animals concentrated Mirex. Three photoproducts accumulated on the bait particles, and both oysters and one species of fish accumulated one of the photoproducts.


Revisiting the Energy-Happiness Paradox: A Quasi-Experimental Evidence of Electricity Access in Indonesia.
This study revisits the energy-happiness paradox hypothesis using the context of a developing nation. We used Indonesia as a case study, a unique archipelagic country with sparse subnational energy infrastructure, leading to the persistent regional energy access gap. We employed an instrumental variable technique to obviate conventional bias in the happiness regression. The model utilised a newly available national-level household survey on life satisfaction and historical data on digital maps of Indonesia's electricity infrastructure conditions in 1985. Unlike the phenomena known as the energy-happiness paradox found mainly in the developed countries that suggest the null relationship between having energy access and people's happiness, our finding reveals a positive effect of electricity access on people's happiness. We also show that the mechanism in which the effect operates is through individuals' satisfaction with housing conditions. The heterogeneity analysis shows that the impact of electricity access on happiness is more prominent in the lagging region. It justifies the placed-based policy strategy by the government in developing countries for expanding electricity access in favour of disadvantaged areas.


YouTube as a source of patient information for stroke: A content-quality and an audience engagement analysis.
Stroke is the second leading cause of death worldwide following ischemic heart disease, and the fifth in the United States. The video-sharing database, YouTube, is the second most popular visited website with more than 2 billion users, thus it's increasingly being used as a medium for delivering health information. We aimed to evaluate the quality, reliability and audience engagement of stroke-related YouTube videos. In October 2019 we conducted a search on YouTube using 5 keywords: stroke, brain attack, hemorrhagic stroke, ischemic stroke and transient ischemic attack. We selected the first 30 videos from each search query for further analysis. The validated DISCERN instrument was used (a score of 0-5 per question) to assess the videos by four independent raters. We then recorded qualitative data and quantitative data for each video. After sorting through 150 stroke videos, a total of 101 unique YouTube videos met our inclusion criteria. We found that the mean overall quality of YouTube videos according to DISCERN is of fair quality. Most videos (65.3%) were uploaded by hospitals, mentioned the symptoms of stroke (66.3%), had a doctor speaking (60.4%) and contained diagrams (20.8%). YouTube is a useful source of gathering information about treatment choices for patients and their families as the quality of YouTube videos is fair. The audience engagement suggestions in our paper may help content creators improve the appeal of YouTube videos.


Effects of subinhibitory concentrations of ciprofloxacin on Staphylococcus saprophyticus adherence and virulence in urinary tract infections.
Staphylococcus saprophyticus is a frequent cause of both uncomplicated and complicated urinary tract infections (UTI) in young females and has recently been established as the most prominent gram-positive uropathogen. Although the effects of subinhibitory concentrations of antimicrobials on numerous other pathogenic bacteria have been studied, little is known regarding how S saprophyticus responds under such conditions. In this study, we investigated the effects of subminimum inhibitory concentrations (MIC) of ciprofloxacin (CIP) on S saprophyticus attachment to glass microscope slides, ureteral stent material, and T24 bladder cells, as well as its effects on S saprophyticus-induced proinflammatory cytokine expression in bladder cells. Adherence to glass microscope slides, ureteral stent material, and bladder cell monolayers were all significantly increased in the presence of sub-MIC levels of CIP. While the S saprophyticus challenge of T24 bladder cell monolayers significantly upregulated both interleukin (IL)-6 and IL-8 expression, sub-MIC CIP abrogated these effects, returning their secretion to control levels. Our results demonstrate that exposure to sub-MIC CIP increases S saprophyticus adherence to both abiotic and biotic surfaces including urinary device material and cultured bladder cells. In addition, low levels of this antimicrobial downregulate S saprophyticus-stimulated proinflammatory cytokine secretion in the bladder. These changes may make S saprophyticus more effective at colonizing the urinary tract and highlights the need for clinicians to consider the impact of subinhibitory concentrations of antimicrobials on bacteria when designing treatment strategies to manage UTI.


[Perspective of General Practitioners on Management of Non-dialysis Chronic Kidney Disease - a Qualitative Study].
Chronic Kidney Disease (CKD) is a common diagnosis in older age due to age dependent kidney function decline, as well as an increase in causative diseases like diabetes mellitus and arterial hypertension. The condition knows a long asymptomatic phase in the early stages, and only a small part of the patient will progress to end stage renal disease requiring renal replacement therapy. Patients with CKD are generally managed by General Practitioners (GPs). The aim of the study was to evaluate the perspectives of German GPs on management of patients with non-dialysis CKD. There were 5 focus group discussions with a maximum of 5 GPs (n = 22). The material was recorded and transcribed to be analyzed by content analysis. The most important treatment measures at the CKD were the optimization of causative diseases, medication adjustment and referral for nephrologist consultation. GPs stressed the individual management of their CKD patients. GPs reported that their decisions about CKD management were based on Individual patient factors such as high age or multimorbidity.


Global and local spatial landmarks: their role during foraging by Columbian ground squirrels (Spermophilus columbianus).
Locating food and refuge is essential for an animal's survival. However, little is known how mammals navigate under natural conditions and cope with given environmental constraints. In a series of six experiments, I investigated landmark-based navigation in free-ranging Columbian ground squirrels (Spermophilus columbianus). Squirrels were trained individually to find a baited platform within an array of nine identical platforms and artificial landmarks set up on their territories. After animals learned the location of the food platform in the array, the position of the latter with respect to local artificial, local natural, and global landmarks was manipulated, and the animal's ability to find the food platform was tested. When only positions of local artificial landmarks were changed, squirrels located food with high accuracy. When the location of the array relative to global landmarks was altered, food-finding accuracy decreased but remained significant. In the absence of known global landmarks, the presence of a familiar route and natural local landmarks resulted in significant but not highly accurate performance. Squirrels likely relied on multiple types of cues when orienting towards a food platform. Local landmarks were used only as a secondary mechanism of navigation, and were not attended to when a familiar route and known global landmarks were present. This study provided insights into landmark use by a wild mammal in a natural situation, and it demonstrated that an array of platforms can be employed to investigate landmark-based navigation under such conditions.


Decision-Making in Clinical Practice: Oral Anticoagulant Therapy in Patients with Non-valvular Atrial Fibrillation and a Single Additional Stroke Risk Factor.
Approximately 1 in 3-4 patients presenting with an ischemic stroke will also have atrial fibrillation (AF), and AF-related strokes can be effectively prevented using oral anticoagulant therapy (OAC), either with well-controlled vitamin K antagonists (VKAs) or non-vitamin K antagonist oral anticoagulants (NOACs). In addition, OAC use (both VKAs and NOACs) is associated with a 26% reduction in all-cause mortality (VKAs) or an additional 10% mortality reduction with NOACs relative to VKAs. The decision to use OAC in individual AF patient is based on the estimated balance of the benefit from ischemic stroke reduction against the risk of major OAC-related bleeding [essentially intracranial hemorrhage (ICH)]. Better appreciation of the importance of VKAs' anticoagulation quality [a target time in therapeutic range (TTR) of ≥70%] and the availability of NOACs (which offer better safety compared to VKAs) have decreased the estimated threshold for OAC treatment in AF patients towards lower stroke risk levels. Still, contemporary registry-based data show that OAC is often underused in AF patients at increased risk of stroke. The uncertainty whether to use OAC may be particularly pronounced in AF patients with a single additional stroke risk factor, who are often (mis)perceived as having a "borderline" or insufficient stroke risk to trigger the use of OAC. However, observational data from real-world AF cohorts show that the annual stroke rates in such patients are higher than in patients with no additional stroke risk factors, and OAC use has been associated with reduction in stroke, systemic embolism, or death in comparison to no therapy or aspirin, with no increase in the risk of bleeding relative to aspirin. In this review article, we summarize the basic principles of stroke risk stratification in AF patients and discuss contemporary real-world evidence on OAC use and outcomes of OAC treatment in AF patients with a single additional stroke risk factor in various real-world AF cohorts.


Quantitative Systems Toxicology Approaches to Understand and Predict Drug-Induced Liver Injury.
The DILI-sim Initiative is a public-private partnership using quantitative systems toxicology to build a model (DILIsym) capable of understanding and predicting liver safety liabilities in drug candidates. The effort has provided insights into mechanisms underlying dose-dependent drug-induced liver injury (DILI) and interpatient differences in susceptibility to dose-dependent DILI. DILIsym may be useful in identifying drugs capable of causing idiosyncratic hepatotoxicity. DILIsym is used to optimize interpretation of traditional and newer serum biomarkers of DILI. DILIsym results are considered in drug development decisions. In the future, it may be possible to use DILsym predictions to justify reduction in size of some clinical trials.


Calmodulin is tightly associated with synaptic vesicles independent of calcium.
A protein in highly purified synaptic vesicles from elasmobranch electric organ is recognized by two specific antisera that recognize different determinants of calmodulin. The protein is indistinguishable from authentic calmodulin by migration on sodium dodecyl sulfate-polyacrylamide gel electrophoresis in the presence or absence of calcium. It is tightly associated with the intact synaptic vesicle membrane even in the absence of calcium. It is on vesicles rather than membrane contaminants and cytoplasmically oriented since a calmodulin antibody (sheep anti-calmodulin antibody) immunoprecipitates at least 86% of intact synaptic vesicles. Surprisingly, another calmodulin antiserum (rabbit anti-calmodulin serum) specifically precipitates less than 20% of the intact vesicles. This antiserum (rabbit anti-calmodulin serum) also detects 4-15 times less calmodulin immunoreactivity than sheep anti-calmodulin antibody by radioimmunoassay of vesicles solubilized with nondenaturing detergents. The difference essentially disappears if the vesicle calmodulin is solubilized in sodium dodecyl sulfate. We suggest that the antigenic determinant recognized by rabbit anti-calmodulin serum is concealed in vesicle-associated calmodulin and may be involved in binding calmodulin to the vesicle.


Preservation of GABAergic perikarya and boutons after transient ischemia in the gerbil hippocampal CA1 field.
Using an antibody directed against the gamma-aminobutyric acid (GABA)-synthetizing enzyme glutamate decarboxylase (GAD) the fate of the GABAergic innervation was investigated in the hippocampal field CA1 of gerbils up to 14 days after a bilateral transient 5-min occlusion of carotid arteries. As described previously, the CA1 pyramidal cells were subject to the ischemia-induced delayed neuronal death, the first signs of which were detectable after 2 days and which was fully developed after 4 days. Local GAD-immunoreactive neurons and boutons, however, exhibited no changes in their distribution and morphology over the whole 14-day period investigated, as studied both at the light and electron microscopic level. Thus, it can be assumed that the increased excitation observed during the development of delayed neuronal death, is not due to a loss of GABAergic neuronal profiles. The resistance of the GABAergic neurons to the ischemic insult is discussed in relation to the presence of Ca2+-binding proteins in this class of neurons, and the long persistence of innervation in an area nearly devoid of postsynaptic targets is considered.


[Determining conjugated bile acids by reverse HPLC and analyzing the conjugated bile acids in sera of patients with hepatocirrhosis].
To investigate the conjugated bile acids in sera of patients with hepatocirrhosis by the determination of conjugated bile acids using reverse HPLC(high performance liquid chromatography). Reverse HPLC was used to determine the conjugated bile acids, to evaluate the precision, accuracy, sensitivity and linear limitation of the method, and to separate and determine six conjugated bile acids in the sera of hepatocirrhotic patients. A comparison with controls was performed. The limitation of determination was 3.125 mumol/L. The coefficients of variation were less than 10% within day and less than 15% day to day for the concentration (3.5-100 mumol/L) of bile acids, and the recoveries were 93.3%-106.1% except TLCA. The concentrations of conjugated bile acids in sera of patients with hepatocirrhosis were significantly higher than those of the control group (P < 0.05). The method can meet the need of the determination of conjugated bile acids in serum. The concentrations of conjugated bile acids in sera of patients with hepatocirrhosis are of use for clinical diagnosis and treatment.


Extreme rainfall reduces one-twelfth of China's rice yield over the last two decades.
Extreme climate events constitute a major risk to global food production. Among these, extreme rainfall is often dismissed from historical analyses and future projections, the impacts and mechanisms of which remain poorly understood. Here we used long-term nationwide observations and multi-level rainfall manipulative experiments to explore the magnitude and mechanisms of extreme rainfall impacts on rice yield in China. We find that rice yield reductions due to extreme rainfall were comparable to those induced by extreme heat over the last two decades, reaching 7.6 ± 0.9% (one standard error) according to nationwide observations and 8.1 ± 1.1% according to the crop model incorporating the mechanisms revealed from manipulative experiments. Extreme rainfall reduces rice yield mainly by limiting nitrogen availability for tillering that lowers per-area effective panicles and by exerting physical disturbance on pollination that declines per-panicle filled grains. Considering these mechanisms, we projected ~8% additional yield reduction due to extreme rainfall under warmer climate by the end of the century. These findings demonstrate that it is critical to account for extreme rainfall in food security assessments.


Minimal-invasive approach to study pulmonary, metabolic and renal responses to alimentary acid-base changes in conscious rabbits.
Systemic acid-base balance is maintained by the complex interplay of renal and pulmonary control functions and metabolic adaptations, whereby intake and mineral composition of feed are important factors. It was intended to explore the role of alimentary acid-base load and carbonic anhydrase activity for regulatory responses of renal, pulmonary or metabolic origin in rabbits as typical herbivores. Sixty-eight conscious male rabbits (about 3.5 kg) were kept in a metabolic cage, to determine daily water intake, urine excretion and food consumption. Different groups were fed either alkali-rich rabbit standard pellets, or modified rabbit chow with low Ca++-content, or a special diet with very low alkali content, or standard food together with a low oral dose (about 20 mg x kg(-1) x d(-1)) acetazolamide. Samples from the central ear artery were analyzed for blood gases (PaO2, PaCO2), pHa, base excess (BE) and actual bicarbonate (HCO3a-). The metabolic CO2 production (VCO2 STPD) was determined, to calculate alveolar ventilation (VA BTPS). Anaerobically collected urine was analyzed for pHu and for concentrations of bicarbonate/carbonate (HCO3-/CO3--), ammonium (NH4+), and phosphate. 1) Systemic BE was not affected by alimentary alkali load, either varied spontaneously by standard food intake or by the low-Ca++ diet, and decreased only slightly on the low-alkali diet, but distinctly upon carbonic anhydrase inhibition. 2) Under all conditions of alimentation, PaCO2 was closely correlated with BE without a detectable set-point, the normal-range variability of BE being sufficient to elicit corresponding changes in VA. In contrast, acetazolamide led to much lower values of PaCO2 than predicted by the reference PCO2/BE relationship, being primarily caused by significant reductions in VCO2 (> 20%). 3) Prior to other systems, renal base excretion, normally being high on species-adapted standard chow, closely followed any variation of alimentary alkali load and approached zero upon the low-alkali diet. It was, however, not significantly influenced by carbonic anhydrase (CA) inhibition on alkalirich alimentation. Blood acid-base balance in rabbits is maintained over a wide range of alimentary alkali load by effective adaptation of renal base excretion, independent of CA activity. Ventilatory pH control is perpetuated even in the normal range of BE, provided metabolic rate is not impaired, e. g., by CA inhibition. These results may help one understand the different manifestations of acid-base disorders in body fluids under clinical conditions.


Electrophysiologic effects of desethylamiodarone, an active metabolite of amiodarone: comparison with amiodarone during chronic administration in rabbits.
During acute superfusion studies by means of the standard microelectrode technique, we previously showed that both amiodarone and its major metabolite, desethylamiodarone, had a modest effect on the lengthening of the action potential duration (APD) at high drug concentrations and produced a rate-dependent block of the sodium channel in cardiac muscle. In this study the comparative electrophysiologic effects of the two compounds in rabbits treated chronically with these compounds were determined with particular reference to repolarization and sinus node automaticity. The changes were correlated with those in serum and tissue drug levels and in thyroid hormone indices. After 1 week neither compound had a significant effect on atrial or sinus nodal potentials; after 3 weeks, amiodarone increased the atrial APD at 90% repolarization time by 10.5% (p less than 0.05) and the effective refractory period (ERP) by 6.7% (p less than 0.05). The corresponding figures for desethylamiodarone were 13% (NS) and 18% (NS). The sinus cycle length was increased 12% (NS) by amiodarone and 27.9% (p less than 0.05) after the metabolite. In animals treated for 6 weeks, amiodarone increased the ventricular APD at 90% repolarization by 58.8% (p less than 0.01) and desethylamiodarone by 42.0% the corresponding figures for the ERP were 63.4% (p less than 0.01 and 47.4% (p less than 0.01), respectively. At the stimulation frequency used, neither compound exerted a significant effect on Vmax. Both amiodarone and desethylamiodarone significantly decreased serum triiodothyronine and increased reverse triiodothyronine levels but had no effect on thyroxine.(ABSTRACT TRUNCATED AT 250 WORDS)


Comparison of Intraocular Antibody Measurement, Quantitative Pathogen PCR, and Metagenomic Deep Sequencing of Aqueous Humor in Secondary Glaucoma Associated with Anterior Segment Uveitis.
To identify viral pathogens in patients with secondary glaucoma associated with anterior segment uveitis and compare metagenomic deep sequencing (MDS) with enzyme-linked immunosorbent assay (ELISA) combined with Witmer-Desmonts coefficient (WDC) evaluation and real-time quantitative polymerase chain reaction (qPCR) on investigating pathogens in aqueous humor. Aqueous humor from 31 patients, including 22 Posner-Schlossman Syndrome and 9 other anterior uveitis, was assessed pathogens by ELISA combined with WDC evaluation, virus deoxyribonucleic acid (DNA) detection by real-time qPCR and MDS. Viral pathogens (HCMV or VZV or RV) were detected in 19 out of 31 eyes (61.3%) by real-time qPCR or WDC evaluation. MDS revealed the presence of HCMV DNA sequences in three PSS patients. Virus is an important pathogen in secondary glaucoma associated with anterior segment uveitis. MDS is a potential etiologic diagnosis tool to seek intraocular viral pathogens for secondary glaucoma associated anterior segment uveitis.


Antigenic determinant(s) shared by the human Thy 1 and human IgG.
A human T cell differentiation antigen (p25) previously described as being the mouse theta equivalent has been examined for shared antigenic determinants with immunoglobulin. A strong cross-reactivity of an antiserum prepared against p25 antigen was established with human IgG subclasses. This antiserum does not react with human IgM or IgA, nor with primate immunoglobulins. The shared determinants appear to be associated with the disulphide-bonded cysteines in the first and third constant domains of the IgG molecule and the 9-112 disulfide bond of Thy 1.


Retroperitoneal lymphadenectomy and aggressive chemotherapy in nonbulky clinical Stage II nonseminomatous germinal testis tumors.
In a former series of 60 resected Stage II nonseminomatous germinal testis tumors the authors succeeded in demonstrating that adjuvant cisplatin, vinblastine, and bleomycin (PVB) was able to significantly improve survival (100% in 11 treated versus 28.5% in 7 historical controls, P less than 0.01) only in patients with retroperitoneal metastases greater than 5 cm, macroscopic extranodal spread, tumor invasion into retroperitoneal veins (pathologic Stage II-C). Forty-eight evaluable patients with clinical nonbulky Stage II nonseminomatous testis cancer underwent retroperitoneal lymphadenectomy as primary treatment. Four courses of postoperative PVB were administered only to 18 clinically understaged patients (14 pathologic Stage II-C, and 4 postoperatively reclassified as Stage III). The remaining 30 patients were followed at monthly intervals. After a median follow-up of 25 months, relapses were: 1 (10%) in 10 pathologic Stage I patients; 8 (40%) in 20 pathologic Stage II-A and II-B; null in the 18 treated. Eight of the nine patients (89%) who had relapse entered continuous complete remission following salvage therapy. The overall 2-year disease-free survival in this case series is 98%. Retroperitoneal lymphadenectomy followed by compulsive follow-up and selective use of aggressive chemotherapy is an alternative to remission induction chemotherapy as primary treatment in clinical nonbulky Stage II nonseminomatous testis cancer, and to immediate adjuvant chemotherapy in all patients with resected Stage II disease.


[THE BIG CHALLENGES OF PEDIATRIC NEPHROLOGY AT THE OUTSET OF THE THIRD DECADE OF THE 21ST CENTURY].
Over the past few decades, there have been tremendous advancements in the field of nephrology due to developments in genetics and molecular biology, such as the ability to pinpoint the causative mutations in congenital syndromes involving the kidneys, animal models of kidney disease and an array of tools for manipulating nucleic acids. However, despite these achievements, in most cases, these sophisticated technologies have yet to translate into improved outcomes. Thus, there are still several important challenges in the field of pediatric nephrology, the most important of which are reviewed herein. These include: 1. Better understanding of the association between a specific genotype and disease phenotype in congenital anomalies of the kidney and urinary tract, and development of effective treatments for these anomalies. 2. Deeper understanding of the pathophysiology of genetic kidney diseases. 3. Application of the available molecular tools for the purpose of genetic treatments of congenital kidney disease. 4. Uncovering the underlying mechanisms of renal fibrosis and establishment of effective means of halting/preventing it. Advancements in any of these areas have a great potential to influence the prognosis of children with kidney diseases, and considering the fast pace in which new knowledge is acquired and technologies are developed, it is expected that at least some of these challenges will be met in the foreseeable future.


Steady-state transcript levels of cytochrome c oxidase genes during human myogenesis indicate subunit switching of subunit VIa and co-expression of subunit VIIa isoforms.
Steady-state levels of the mitochondrial rRNAs, of mRNAs for mitochondrially and nuclear-encoded subunits of cytochrome c oxidase and for the beta subunit of ATP synthase were assessed by Northern blot hybridizations during the in vitro differentiation of human myoblasts. Transcript levels of the so-called liver-type form of subunit VIa of cytochrome c oxidase diminished during the course of differentiation, while transcription of the so-called heart-type form was induced. Transcripts for the liver-type form and for the heart-type form of subunit VIIa of cytochrome c oxidase were detected in all myogenic cultures; the levels of the heart-type form progressively increased during the course of differentiation. The levels of the other transcripts studied did not change substantially. The results suggest subunit switching of subunit VIa and co-expression of subunit VIIa isoforms during myogenesis. The differential changes in mRNA levels of the heart-type subunits VIa and VIIa and the differential changes in mRNA levels of the liver-type subunits VIa and VIIa demonstrate that different transcriptional regulation mechanisms are present for both heart-type genes as well as for both liver-type genes.


State Authenticity as Fit to Environment: The Implications of Social Identity for Fit, Authenticity, and Self-Segregation.
People seek out situations that "fit," but the concept of fit is not well understood. We introduce State Authenticity as Fit to the Environment (SAFE), a conceptual framework for understanding how social identities motivate the situations that people approach or avoid. Drawing from but expanding the authenticity literature, we first outline three types of person-environment fit: self-concept fit, goal fit, and social fit. Each type of fit, we argue, facilitates cognitive fluency, motivational fluency, and social fluency that promote state authenticity and drive approach or avoidance behaviors. Using this model, we assert that contexts subtly signal social identities in ways that implicate each type of fit, eliciting state authenticity for advantaged groups but state inauthenticity for disadvantaged groups. Given that people strive to be authentic, these processes cascade down to self-segregation among social groups, reinforcing social inequalities. We conclude by mapping out directions for research on relevant mechanisms and boundary conditions.


Survival and prognosis of surgical head and neck cancer patients aged 80 years and older.
Elderly patients (≥80 years of age) with head and neck cancer (HNC) can prove a management challenge due to concerns regarding their suitability for surgery. This study aims to describe the characteristics and outcomes of elderly patients undergoing HNC surgery. A retrospective review of elderly patients undergoing HNC surgery was conducted. Demographics, comorbidities, tumor characteristics, surgical procedure type, postoperative complications, and disposition were reviewed. Overall survival (OS) in the elderly cohort was compared against younger patients (<80 years). A total of 595 patients were included, of whom 86 were aged >80 years (71% male; mean age 84.8, range 80.0-98.8 years). The overall complication rate was 43%. When compared with younger patients (n = 509), elderly patients had reduced OS (risk ratio: 2.0, 95% CI: 1.3-3.2), higher 90-day mortality (8.1% vs. 2.3%, p = .005), and lower 5-year survival (43.5% vs. 64.1%, p < .001). However, survival was comparable to age-specific life expectancy. There was no difference in OS, 90-day mortality, and 5-year survival when comparing >85 (n = 33) and 80-85 (n = 53) age groups. Chronological age alone should not negatively influence decision-making in HNC surgery the elderly. With careful preoperative selection and optimization, surgery can be performed at acceptable risk with good outcomes in elderly patients. IV.


Measurement of articular cartilage thickness using a three-dimensional image reconstructed from B-mode ultrasonography mechanical scans feasibility study by comparison with MRI-derived data.
The present study aimed to develop a method to measure three-dimensional (3-D) thickness of cartilage (Tc) at the femoral condyle using B-mode ultrasonography (US) and to clarify the feasibility of US in clinical evaluations of articular cartilage by comparing the results with 3-D measurement values using magnetic resonance imaging (MRI) and assessing repeatability. The medial surface of the right knees of two healthy male volunteers (age, 37 and 59 years) and the knees on affected side of three male patients with osteoarthritis (OA) (age, 73, 81 and 83 years) were scanned using B-mode US with the knee flexed at 120°. The range of the angle of probe rotation for the arm was 0-80° and B-mode images (total, 101 images) were acquired every 0.8°. MRI of the knees was also performed using the double echo steady-state sequence. Both US and MRI images were used to create 3-D models of medial femoral condyle articular cartilage. Tc was determined at points 1 mm apart from one another in the US model (Tc-US) and MRI model (Tc-MRI). Tc-US was compared with Tc-MRI and the repeatability of Tc-US was assessed by mean Tc in the specific region of interest of the femoral condyle. Tc-US correlated significantly with Tc-MRI both in volunteers and in OA patients (p < 0.0001 each) and coefficients of correlation were 0.976 and 0.964 for volunteers and OA patients, respectively. The coefficient of variance for mean Tc-US was 4.90%. Our results show that 3-D US measurements of femoral cartilage are reproducible and correlate strongly with MRI measurements.


Non-antiarrhythmic medications for atrial fibrillation: from bench to clinical practice.
Many treatment modalities have been developed over the years for the management of atrial fibrillation (AF). While they are still considered the first line of treatment for suppression of AF, antiarrhythmics often lead to treatment failure, complications and undesired consequences. Pulmonary vein ablation is an invasive procedure which is not always curative. Recently, there have been a variety of studies reporting the potential antiarrhythmic effects of various nonantiarrhythmic agents. This paper aims to provide a comprehensive review of the findings reported thus far about the antiarrhythmic effects of agents which are not antiarrhythmic drugs themselves, but which have been found to offer promise in the prevention and treatment of AF.


Postmarital residence and bilateral kin associations among hunter-gatherers: Pumé foragers living in the best of both worlds.
Dispersal of individuals from their natal communities at sexual maturity is an important determinant of kin association. In this paper we compare postmarital residence patterns among Pumé foragers of Venezuela to investigate the prevalence of sex-biased vs. bilateral residence. This study complements cross-cultural overviews by examining postmarital kin association in relation to individual, longitudinal data on residence within a forager society. Based on cultural norms, the Pumé have been characterized as matrilocal. Analysis of Pumé marriages over a 25-year period finds a predominant pattern of natalocal residence. We emphasize that natalocality, bilocality, and multilocality accomplish similar ends in maximizing bilateral kin affiliations in contrast to sex-biased residential patterns. Bilateral kin association may be especially important in foraging economies where subsistence activities change throughout the year and large kin networks permit greater potential flexibility in residential mobility.


Hairdressing and the prevalence of scalp disease in African adults.
Anecdotal reports suggest that certain scalp disorders are common in Africans and may be associated with hairstyles. This study of 874 African adults in Cape Town was performed to test this hypothesis. A questionnaire was administered and scalp examinations performed, after ethics approval. Participants included 30.9% men and 69.1% women (median age 36.1 years, range 18-99). Most men had natural hair: 91.7% vs. 24.3% women. The majority of men had recent haircuts (< 4 weeks): 74.8% vs. 9.9% women. The overall prevalence of acne (folliculitis) keloidalis nuchae (AKN) was 3.5%: higher in men than women (10.5% vs. 0.3%). AKN prevalence was not associated with whether clippers or blades were used. However, it was associated with haircut symptoms. Haircut-associated symptoms, i.e. at least one episode of transient pimples (or crusts) and bleeding (however small) were reported in 37% and 18.9% of men, respectively. The latter may have implications for disease transmission. Most women (58.7%) had chemically treated hair (49.2% relaxed and 9.6% permed hair) vs. 2.3% men. The prevalences of traction alopecia (TA) and central centrifugal cicatricial alopecia (CCCA) were 22.6% and 1.9%: higher in women (31.7% vs. 2.2% and 2.7% vs. 0%, respectively). CCCA was highest in women > 50 years (6.7% vs. 1.2%). TA prevalence was highest if the usual hairstyle was extensions attached to relaxed hair (48%). We found associations between specific scalp diseases, hairstyles, gender, and age. These associations need further study, better to elucidate determinants and to improve disease prevention and treatment.


Downregulation of ITGA5 inhibits lymphangiogenesis and cell migration and invasion in male laryngeal squamous cell carcinoma.
ITGA5, a fibronectin receptor was highly expressed in laryngeal squamous cell carcinoma (LSCC) samples and was related to poor survival. However, the potential mechanism remains unclear. To elucidate the regulatory role of ITGA5 in LSCC progression, we investigated the effect of ITGA5 expression on lymphangiogenesis, migration, and invasion of LSCC cells in vitro and in vivo using immunohistochemistry, siRNA transfection, qRT-PCR, western blotting, enzyme-linked immunosorbent assay, flow cytometry, transwell co-culture, tube formation, cell migration, and invasion assays, and a subcutaneous graft tumor model. The expression of ITGA5 was higher in the LSCC tissues and linked to lymph node metastasis and T staging. Moreover, ITGA5 expression was significantly positively correlated with VEGF-C expression, and the lymphatic vessel density of patients with high ITGA5 expression was noticeably higher than that of patients with low ITGA5 expression. Additionally, it was found in vitro that downregulation of ITGA5 expression not only inhibited the expression and secretion of VEGF-C, but also suppressed the tube-forming ability of human lymphatic endothelial cells (HLECs) and the migration and invasion ability of LSCC cells, while exogenous VEGF-C supplementation reversed these phenomena. Furthermore, a tumor xenograft assay showed that si-ITGA5 restrained the growth and metastasis of TU212-derived tumors in vivo. Our findings suggested that ITGA5 induces lymphangiogenesis and LSCC cell migration and invasion by enhancing VEGF-C expression and secretion.


[Visceral leishmaniasis: an update].
During the last decade, visceral leishmaniasis has been reconsidered in its epidemiology and strategies for diagnosis, treatment and prevention. This vectorial disease, responsible for more than 50,000 deaths each year across India, East Africa, South America, the Mediterranean area, Central Asia and China, is currently spreading over new territories. This formerly rural disease has even reached cities in South America. This spreading is caused by environmental changes due to global warming or human activity, and by the movement of workers and refugees. As a consequence, the burden of HIV/Leishmania coinfection is increasing in many developing countries even though effective antiretroviral therapy has led to a marked decrease in its incidence in Europe. The disease is now handled differently than it was 10 years ago: PCR has become the most accurate tool for diagnosis and follow-up in developed countries, and field diagnostic tools have been developed (antigenuria, rK39 dipstick). While resistance to antimoniate has appeared in India and Europe, new therapies have been evaluated such as miltefosine, the first oral therapy, or short treatment with liposomal amphotericin B. In France, liposomal amphotericin B has supplanted antimoniate meglumine because of better tolerance and shorter hospitalization duration. Protecting dogs through immunization or collars impregnated with deltamethrin proved effective to prevent zoonotic leishmaniasis due to Leishmania infantum.


High-performance liquid chromatographic determination of quercetin in human plasma and urine utilizing solid-phase extraction and ultraviolet detection.
An HPLC method for determining quercetin in human plasma and urine is presented for application to the pharmacokinetic study of rutin. Isocratic reversed-phase HPLC was employed for the quantitative analysis by using kaempferol as an internal standard. Solid-phase extraction was performed on an Oasis HLB cartridge (>95% recovery). The HPLC assay was carried out using a Luna ODS-2 column (150 x 2.1 mm I.D., 5 microm particle size). The mobile phase was acetonitrile-10 mM ammonium acetate solution containing 0.3 mM EDTA-glacial acetic acid, 29:70:1 (v/v, pH 3.9) and 26:73:1 (v/v, pH 3.9) for the determination of plasma and urinary quercetin, respectively. The flow-rate was 0.3 ml/min and the detection wavelength was set at 370 nm. Calibration of the overall analytical procedure gave a linear signal (r>0.999) over a concentration range of 4-700 ng/ml of quercetin in plasma and 20-1000 ng/ml of quercetin in urine. The lower limit of quantification was approximately 7 ng/ml of quercetin in plasma and approximately 35 ng/ml in urine. The detection limit (defined at a signal-to-noise ratio of about 3) was approximately 0.35 ng/ml in plasma and urine. A preliminary experiment to investigate the plasma concentration and urinary excretion of quercetin after oral administration of 200 mg of rutin to a healthy volunteer demonstrated that the present method was suitable for determining quercetin in human plasma and urine.


[Autologous transfusion in scoliosis operations: preoperative autologous blood donations and intraoperative mechanical autotransfusion].
Autologous transfusion was used to reduce the high demand for blood accompanied with scoliosis surgery. Half of the blood loss could be saved by intraoperative autotransfusion (35 patients). This resulted in a corresponding reduction in homologous transfusion. An elimination of the need for homologous blood could be achieved only by the combination of preoperative blood donation and intraoperative autotransfusion (37 patients). With freezing the predeposit blood was independent of storage time and autologous plasma was available. Thus, the risks of transfusion can be avoided.


Blunt Traumatic Abdominal Wall Hernias: A Surgeon's Dilemma.
Traumatic abdominal wall hernias (TAWH) have been recognized for more than a century since they were first reported by Selby (JAMA 47:1485-1486, 1906). They continue to be a rare diagnosis, encountered in approximately 1% blunt trauma admissions. The present study is a 10-year retrospective review of patients presenting with TAWH to a State Major Trauma Unit in Western Australia. We hypothesized that the timing of the repair of TAWH was dependent on the severity of the abdominal wall injury, as well as associated injuries, and in turn, this may affect patient outcomes. The Trauma Registry at Royal Perth Hospital (the only Level I Trauma Centre for adults in Western Australia) was scrutinized for TAWH, between 2003 and 2013. The injuries were graded by the classification system of Dennis et al. (Am J Surg 197:413-417, 2009). Patients with TAWH following penetrating trauma were excluded. During the study period, 44 patients were diagnosed to have TAWH accounting for 0.08% of admissions. Thirty (68%) of the patients were male and the median age was 36 years (IQR 24-54). The median BMI was between 25 and 30. The majority of the patients sustained trauma secondary to motor vehicle crashes and the commonest associated injury was a pelvic fracture. Grades 3 and 4 injuries were found to have an association with a pelvic fracture (p < 0.001). No association was seen in the present study between seat belt use and the development of TAWH or between the location of TAWH and seat belt pattern. The median time of diagnosis of TAWH following arrival to hospital was 18 hours while the median time of surgery from diagnosis was 15.5 hours. Forty-one (93%) of the patients underwent surgery. Of these, 8 (20%) were emergent due to a simultaneous bowel perforation and another five had primary mesh repairs. Three of the patients suffered superficial complications (7.5%) and there were 3 (7%) recurrences at a mean time of 7.25 months from the first repair. The follow-up period ranged from 1 to 51 months with an average time of 16 months. This series is the largest single institution study conducted on TAWH to date. Despite its retrospective nature and small numbers, it has generated some important questions. A larger prospective study with a longer follow-up period is required to generate reliable treatment algorithms as well as to standardize the management of TAWH.


Primary hydatid cyst of the maxillary sinus.
An unusual case of hydatid cyst of the maxillary sinus compressing the orbit is presented. No similar report has appeared in world literature.


Extracellular Gd-CA: differences in prevalence of NSF.
Until recently it was believed that extracellular gadolinium-based contrast agents were safe for both the kidneys and all other organs within the dose range up to 0.3 mmol/kg body weight. However, in 2006, it was demonstrated that some gadolinium-based contrast agents may trig the development of nephrogenic systemic fibrosis, a generalized fibrotic disorder, in renal failure patients. As no prospective studies can be performed we must rely on retrospective data. From those data it is obvious that the prevalence of NSF is significantly higher after the unstable agent gadodiamide than after any other gadolinium-based agent (3-7% versus 0-1% per injection) in patients with reduced renal function. Prevalence after exposure to two gadodiamide injections is as high as 36% in patients with chronic kidney disease (CKD) stage 5. No report of NSF after the most stable agents has been reported in the peer-reviewed literature documenting that there is a difference between the various agents regarding triggering NSF.


Dissemination of Metarhizium anisopliae of low and high virulence by mating behavior in Aedes aegypti.
Dengue is a viral disease transmitted by Aedes mosquitoes. It is a threat for public health worldwide and its primary vector Aedes aegypti is becoming resistant to chemical insecticides. These factors have encouraged studies to evaluate entomopathogenic fungi against the vector. Here we evaluated mortality, infection, insemination and fecundity rates in A. aegypti females after infection by autodissemination with two Mexican strains of Metarhizium anisopliae. Two M. anisopliae strains were tested: The Ma-CBG-1 least virulent (lv), and the Ma-CBG-2 highly virulent (hv) strain. The lv was tested as non mosquito-passed (NMP), and mosquito-passed (MP), while the hv was examined only as MP version, therefore including the control four treatments were used. In the first bioassay virulence of fungal strains towards female mosquitoes was determined by indirect exposure for 48 hours to conidia-impregnated paper. In the second bioassay autodissemination of fungal conidia from fungus-contaminated males to females was evaluated. Daily mortality allowed computation of survival curves and calculation of the LT50 by the Kaplan-Meier model. All combinations of fungal sporulation and mating insemination across the four treatments were analyzed by χ2. The mean fecundity was analyzed by ANOVA and means contrasted with the Ryan test. Indirect exposure to conidia allowed a faster rate of mortality, but exposure to a fungal-contaminated male was also an effective method of infecting female mosquitoes. All females confined with the hv strain-contaminated male died in fifteen days with a LT50 of 7.57 (± 0.45) where the control was 24.82 (± 0.92). For the lv strain, it was possible to increase fungal virulence by passing the strain through mosquitoes. 85% of females exposed to hv-contaminated males became infected and of them just 10% were inseminated; control insemination was 46%. The hv strain reduced fecundity by up to 99%, and the lv strain caused a 40% reduction in fecundity. The hv isolate infringed a high mortality, allowed a low rate of insemination, and reduced fecundity to nearly zero in females confined with a fungus-contaminated male. This pathogenic impact exerted through sexual transmission makes the hv strain of M. anisopliae worthy of further research.


A phase 3 clinical trial of MINHAI PCV13 in Chinese children aged from 7 months to 5 years old.
Pneumococcus lead to various kinds of invasive disease such as pneumonia, otitis media, meningitis, bacteremia and so on. It has been a great threat to children under 5. A new 13-valent pneumococcal conjugate vaccine (PCV13) with carrier tetanus toxoid and diphtheria toxoid was developed by MINHAI, aiming to prevent pneumococcus infection. In this study, we reported the safety and immunogenicity of MINHAI PCV13 in Chinese children aged from 7 months to 5 years old. A randomized, double-blinded, parallelized phase III clinical trial was operated in 900 participants. Haemophilus influenzae type B conjugate vaccine (Hib) served as negative control. PCV13 and Hib were intramuscular injected to participants at a ratio of 2:1. Local and systemic adverse events (AEs) and severe adverse events (SAEs) were recorded to evaluate the safety of PCV13. Blood samples were collected before and after immunization for the detecting of serotype-specific anti-polysaccharide immunoglobulin (Ig)G and opsonophagocytosis assay (OPA). The proportion of IgG concentration ≥ 0.35 μg/mL (IgG positive rate), IgG geometric mean concentration (GMC), OPA geometric mean titer (GMT), and other indicators were analyzed to evaluate the immunogenicity of PCV13. During the study period, no PCV13 associated SAE happened. Incidences of several AEs in PCV13 groups were higher than the Hib groups, but most of them were mild or moderate. For all 13 serotypes, IgG and OPA indicators of the PCV13 groups were generally superior to the Hib groups, and the differences were mostly statistically significant, which indicates that MINHAI PCV13 can effectively induce pneumococcal specific antibody. The study demonstrates that MINHAI PCV13 has sufficient immunogenicity and safety in Chinese children aged from 7 months to 5 years old. NCT02494999.


Relative frequency and survival results of cancer seen at a county hospital.
The relative frequency of cancer cases (percentage of total malignancies) admitted to Los Angeles County-University of Southern California (LAC-USC) Medical Center from 1942 to 1974 was studied (basal cell and epidermoid carcinoma of the skin were excluded). Among cancers of the digestive system, the relative frequency of cancer of the stomach has definitely declined from a high of 9.5% before 1946 to a low of 2% in 1972. Carcinoma of the colorectum has shown a downward trend in the last decade. Among cancers of the respiratory system, cancer of the lung continues its steady increase from a relative frequency of 7% before 1946 to a high of 20% in 1974. The percentages of malignant lesions of the female organs (breast, uterine body, ovaries) have stayed relatively constant. Cancers of the central nervous system and malignancy of unknown primary site showed an increasing trend over the last 15 years. The 8 most common cancers according to their relative frequency at Los Angeles County Hospital in 1974 are: colon (10%), rectum (5%), breast (15%), lung (13%), prostate (7%), cervix uteri (6%), stomach (3%), and pancreas (3%). In general, survival results of patients in the California Tumor Registry are comparable with those reported in the national study, and survival rates of patients seen at the Los Angeles County Hospital are lower. But 5 year survival rates have improved by more than 3 percentage points for patients with all stages of cancer of the colon, breast, prostate, and cervix uteri diagnosed at the Los Angeles County Hospital in recent years.


Friendships that money can buy: financial security protects health in retirement by enabling social connectedness.
Research on the health and wellbeing of retirees has tended to focus on financial security and financial planning. However, we suggest that one reason why financial security is important for retirees is that it enables social connectedness, which is critical for healthy ageing. This paper tests this hypothesis cross-sectionally (N = 3109) and longitudinally (N = 404) using a population-weighted mixed effects mediation model in two nationally representative samples of Australian retirees. Analyses provide robust support for our model. Subjective financial security predicted retiree health cross-sectionally and longitudinally. Social connectedness also consistently predicted mental health and physical health, on average four times more strongly than financial security. Furthermore, social connectedness partially accounted for the protective effect of subjective financial security. We discuss the implications of these findings for public health, with a particular emphasis on how social connectedness can be better supported for people transitioning to retirement.


Cardiovascular status and blood pressure in a population sample in Ghana--the Mamprobi survey.
In a medical survey of an urban population in Ghana, abnormal cardiovascular findings were present in 25% of the population aged from 15 to 64 years. This was largely due to hypertension and to cardiomegaly of obscure origin. The prevalence of valvular heart disease was comparatively low. Abnormal cardiovascular findings were commonest in the lowest third of the socio-economic stratum and next most frequent in the highest third. Abnormal findings were not related to smoking or drinking habits; these seem to be only marginally important in the population at present.


The effects of CRF and urocortins on the sociability of mice.
The aim of our study was to determine the role of corticotropin-releasing factor (CRF), the urocortins (Ucn1, Ucn2 and Ucn3) and their receptors (CRF1 and CRF2) in the sociability of mice. Male CFLP mice were administered intracerebroventricularly (icv) with CRF and urocortins alone or in combination with antalarmin (specific CRF1 antagonist) and astressin2B (specific CRF2 antagonist) and then investigated in a Crawley social interaction test arena, that consists of three chambers. An unknown male in a cage was put in the first chamber and an empty cage was put in the opposite chamber. The tested male was habituated with the middle chamber for 5min and then allowed to explore the remaining chambers for 5min, during which the number of entries and the time of interaction were measured. Intracerebroventricular administration of CRF decreased significantly the number of entries and the time of interaction with the unknown male and these effects were blocked by antalarmin, but not astressin2B. In contrast, central administration of Ucn1 increased significantly the number of entries into the chamber of the unknown male, without changing the time of interaction and this effect was blocked by astressin2B, but not antalarmin. Central administration of Ucn2 and Ucn3 didn't influence remarkably the number of entries, but it reduced the time of interaction between the male mice. Our study suggests that CRF and Ucn1 may play important, but different roles in sociability, and that Ucn2 and Ucn3, playing similar roles, must be also involved in social interactions.


Measurements of cefuroxime concentration in bone in dogs and man.
Measurements of Cefuroxime levels performed in dogs show a decrease against time in well perfused tissue similar to that in serum, while in bradytrophic tissue--such as bone and articular capsule--there is a distinct rise of these values in the time scale assessed. In similar investigations in man the higher levels in bradytrophic tissue are attributable to delayed elimination from the compact and spongy bone as compared to the serum. The effect on osteomyelitis, to be derived from this, is discussed.


Effects of organic acids on the photosynthetic and antioxidant properties and accumulations of heavy metals of Melilotus officinalis grown in Cu tailing.
The effect of citric acid (CA), acetic acid (Ac), and ethylene diamine tetraacetic acid (EDTA) on the photosynthetic and antioxidant properties and the accumulation of some heavy metals (HMs) of Melilotus officinalis seedling growing in Cu mine tailings for 25 days were studied. Results showed that the formation of photosynthesizing cells of M. officinalis was inhibited by EDTA at 2 mmol/kg. Photosynthetic pigment contents under EDTA of 2 mmol/kg were reduced by 26, 40, and 19 %, respectively, compared to the control. The proline contents in aboveground and underground parts increased as the level of EDTA was enhanced. CA and Ac enhanced the activities of superoxide dismutase (SOD) and peroxidase (POD) in the aboveground parts and EDTA inhibited the activity of POD in the underground parts. The addition of CA promoted significantly the growth of M. officinalis, while the biomass decreased significantly under 2 mmol/kg EDTA. Cu contents in the aboveground parts treated with 0.5 and 2.0 mmol/kg EDTA reached 175.50 and 265.17 μg/g dry weight, respectively. Ac and EDTA treatments promoted Cd to translocate from root to aboveground parts. The result indicated that M. officinalis was a tolerant species of Cu tailing and can be used to remediate Cu contaminated environment, and rationally utilization of organic acids, especially EDTA, in the phytoremediation can improve the growth and metals accumulation of M. officinalis.


Prenatal exposure to per- and polyfluoroalkyl substances, fetal thyroid hormones, and infant neurodevelopment.
Per- and polyfluoroalkyl substances (PFAS) are believed to impair early neurodevelopment and disrupt thyroid hormone (TH) levels. However, there are limited epidemiological data on the neurodevelopmental effects in infancy of prenatal PFAS exposure and the potential mediating effects of TH. To evaluate potential associations between prenatal PFAS exposure and early neurodevelopmental deficiencies, and assess mediator effects of TH. From 2010 to 2013, 274 mother-infant pairs were recruited to the Laizhou Wan Birth Cohort in China. Ten PFAS and five TH were measured in cord serum. Developmental quotient (DQ) from 5 domains (adaptive, social, language, gross and fine motor) was assessed using Gesell Developmental Schedules for each child at 1 year of age. The associations between PFAS and DQs were evaluated using multivariable linear regressions. TH-mediated effects of PFAS on DQs were calculated by mediation analyses. Among our study population, PFAS exposures were common and associated with DQ decrement in infants. For each 10-fold increase in PFBS concentrations, gross motor and adaptive DQ decreased by 8.56 (95%CI: -15.15, -1.97) and 5.87 (95%CI: -8.07, -3.67) points, respectively. TSH mediated 12.90% of the association of PFBS with gross motor DQ and FT4 explained 19.63% of the association of PFBS with adaptive DQ. The negative association was also found between PFHxS exposure and gross motor DQ (β = 8.14, 95%CI: -15.39, -0.98). PFBS and PFHxS were negatively associated with early neurodevelopment, especially consistent in gross motor domain. The associations were partly explained by TSH and FT4.


[Levels of polychlorinated dibenzo-p-dioxins and dibenzo-furans in sea fish samples in some sea areas in China].
To analyse the levels of polychlorinated dibenzo-p-dioxins and dibenzo-furans (PCDD/Fs) in sea fish samples in some sea area in China surveyed by using isotope dilution HRGC/HRMS and was evaluated the local people with PCDD/Fs exposure from eating fish. Seven different kinds of fish and twenty fishes were sampled totally. Dibenzo-p-dioxins and dibenzo-furans were extracted from fish samples by Soxhlet extraction, concentrated and purified by FMS column chromatograph and enriched by carbon column. Confirmation and quantitative analysis at ng/kg level of PCDD/Fs was performed by HRGC/HRMS using multiple ion detection mode (MID). Carp-2 was the certified reference material obtained from the NRC Institute of Canada. The concentration of 9 compounds was consistent with the certified value, and precision was evaluated in this study. The relative standard deviation was less than 15 percent for three times determination. The average concentration of 20 sea fishes was 1.48 ng/kg wet weight, the range was in 0.21-8.10 ng/kg wet weight, and the average total toxicity equivalency factor (TEQ) was 0.292 ng TEQ/kg (wet weight basis) and the range was 0.030-1.291 ng TEQ/kg for these 20 fishes. The evaluation exposure from fish for local people was 0.58 pg WHO-TEQ/kg BW.day. The levels of PCDD/Fs was different from sample to sample, and the exposure from fish be less than WHO tolerance limit standard, however, the status for PCDD/Fs pollution should not be ignored especially when having an intake of multi-food.


Stress-related hormonal alterations, growth and pelleted starter intake in pre-weaning Holstein calves in response to thermal stress.
This study aimed to investigate the effect of heat stress and month of birth on growth performance, pelleted starter intake, and stress-related hormones in Holstein calves. Birth weight and growth records, representing 4735 Holstein calves from a large commercial dairy herd in northern Mexico (25° N; 22.3 °C mean annual temperature) from 2013 to 2015, were analyzed. Temperature-humidity index (THI) at calving, season of birth, and month of birth were the independent variables, whereas growth traits were the dependent variables. Increased THI at birth from < 65 to > 85 units was associated with a decrease in birth weight from 39.3 to 38.7 kg. Calves subjected to high THI (> 75 units) at calving showed lesser (P < 0.01) pre-weaning gains (405 ± 97 g/calf/day), whereas those calves born with THI < 70 units presented the highest gains (466 ± 112 g/calf/day). Birth during the fall months reduced (P < 0.01) weaning weight by about 5 kg compared with winter months. Also, the pre-weaning average daily gain for calves born in the fall was about 70 g less (P < 0.01) than calves delivered in winter months. Plasma triiodothyronine and tetraiodothyronine levels were lower (1.02 ± 0.21 and 48 ± 7.9 ng/mL, respectively; P < 0.01) in summer and highest in winter (1.64 ± 0.48 and 66 ± 11 ng/mL, respectively). Mean plasma cortisol concentration was higher in heat-stressed calves born in summer (59 ± 40 ng/mL) than calves born in winter (20 ± 28 ng/mL). Pelleted starter intake 1 week before weaning was lowest (P < 0.01) in the fall (0.82 ± 0.26 kg/calf/day; mean ± SD) and highest in spring (1.26 ± 0.43 kg/calf/day). It was concluded that in this particular environment, heat stress affects birth weight and growth rate of Holstein calves. Thus, environmental management of the newborn calf during hot spring and summer months is warranted to optimize pelleted starter intake and calf growth rates.


Diagnosis of temporal lobe epilepsy by positron emission tomography.
Temporal lobe epilepsy was studied by the 11C-glucose method of positron emission tomography. The temporal lobe at the level 25 mm above the orbitomeatal line showed the amygdala, hippocampus and hippocampal gyrus medially, and the T1, T2 and T3 neocortices laterally. The focus locations in these structures were divided into mesial, lateral and combined groups on the PECT images. This classification showed a close correlation between the clinical symptoms and the anatomical focus sites.


Enhanced Visualization of Optimal Cerebral Perfusion Pressure Over Time to Support Clinical Decision Making.
Cerebrovascular reactivity can provide a continuously updated individualized target for management of cerebral perfusion pressure, termed optimal cerebral perfusion pressure. The objective of this project was to find a way of improving the optimal cerebral perfusion pressure methodology by introducing a new visualization method. Four severe traumatic brain injury patients with intracranial pressure monitoring. Data were collected and pre-processed using ICM+ software. Sequential optimal cerebral perfusion pressure curves were used to create a color-coded maps of autoregulation - cerebral perfusion pressure relationship evolution over time. The visualization method addresses some of the main drawbacks of the original methodology and might bring the potential for its clinical application closer.


Effect of soft shell hip protectors on pressure distribution to the hip during sideways falls.
While hip protectors represent a promising strategy for preventing hip fractures, clinical efficacy has been limited by poor user compliance. Soft shell protectors may be more acceptable to users than traditional hard shell designs. However, before embarking on clinical trials to assess efficacy, laboratory experiments are required to determine how soft shell protectors affect the force applied during impact to the hip. This was the goal of the current study. Fifteen women participated in "pelvis release experiments," which safely simulate the impact stage of a sideways fall. During the trials, we measured total impact force and mean pressure over the greater trochanter with the participant unpadded, and while wearing two commercially available soft shell protectors. Mean pressure over the greater trochanter was reduced by 76% by a 14-mm thick horseshoe-shaped protector and by 73% by a 16-mm thick continuous protector. Total force was reduced by 9% by the horseshoe and by 19% by the continuous protector. Soft shell hip protectors substantially reduce the pressure over the greater trochanter, while only modestly reducing total impact force during simulated sideways falls. These data support the need for clinical trials to determine whether soft shell protectors reduce hip fracture risk in vulnerable populations.


Sex Differences in the Blood Concentration of Tacrolimus in Systemic Lupus Erythematosus and Rheumatoid Arthritis Patients with CYP3A5*3/*3.
The purpose of this study was to describe the impact of sex and cytochrome P450 3A5 (CYP3A5) variant on the blood concentration of tacrolimus in patients with systemic lupus erythematosus or rheumatoid arthritis. The blood concentration of tacrolimus (ng/mL) divided by the daily dose of tacrolimus (mg/day) and the patient's weight (kg) (C/D) was obtained from 55 patients. The C/D value was analysed according to genetic variation in CYP3A5 or ATP binding cassette subfamily B member 1 (ABCB1), sex, and age. The C/D value in the CYP3A5*3/*3 group was significantly higher than in the CYP3A5*1/*1 and *1/*3 groups (p < 0.05, effect size: d = 1.40). In the CYP3A5*3/*3 group, the concentration of tacrolimus was significantly higher in men than in women (p < 0.05, effect size: d = 1.78). Furthermore, in the CYP3A5*3/*3 group, the concentration of tacrolimus was significantly higher in women aged over 50 years than in women aged under 50 years (p < 0.05, effect size: d = 1.18). In contrast, ABCB1 genetic variations did not show any significant effect on the C/D value. Since the blood concentration of tacrolimus in patients with CYP3A5*3/*3 varies depending on sex and age, these factors should be considered when studying the difference of sex in CYP3A.


Infectivity of Cryptosporidium hominis and Cryptosporidium parvum genotype 2 isolates in immunosuppressed Mongolian gerbils.
One-month-old dexamethasone-immunosuppressed Mongolian gerbils were challenged with 1 oocyst to 2 x 10(5) oocysts from two isolates genotyped as Cryptosporidium hominis and C. parvum (genotype 2), respectively. A similar dose-dependent gut infection was obtained, and the initial genotype maintained for 21 to 22 days. The data suggest that immunosuppressed gerbils provide a reliable rodent model of persistent C. hominis infection.


The Intersection of Epigenetics and Metabolism in Trained Immunity.
The last few years have witnessed an increasing body of evidence that challenges the traditional view that immunological memory is an exclusive trait of the adaptive immune system. Myeloid cells can show increased responsiveness upon subsequent stimulation with the same or a different stimulus, well after the initial challenge. This de facto innate immune memory has been termed "trained immunity" and is involved in infections, vaccination and inflammatory diseases. Trained immunity is based on two main pillars: the epigenetic and metabolic reprogramming of cells. In this review we discuss the latest insights into the epigenetic mechanisms behind the induction of trained immunity, as well as the role of different cellular metabolites and metabolic networks in the induction, regulation and maintenance of trained immunity.


Unusual arthritis: be on the alert for leprosy.
A 50-year-old Indonesian man presented with arthritis of the left ankle, wrist and hand joints and a diffusely swollen left hand and foot. A few months later granulomatous skin lesions developed and renewed physical examination revealed a paresis of the intrinsic muscles of the left hand and the left M. extensor hallucis longes and thickening of several peripheral nerves. The skin lesions appeared to be anesthetic. A diagnosis of borderline tuberculoid leprosy was made and treatment resulted in cure with permanent peripheral nerve damage. This case emphasizes the importance of early recognition and treatment of leprosy to prevent nerve damage.