Poly(Vinyl Acetate) Paints: A Literature Review of Material Properties, Ageing Characteristics, and Conservation Challenges.
Since their development in the 1950s, poly(vinyl acetate) [PVAc] paints (also known as vinyl) have been used by many artists, most notably in countries such as Spain, Portugal, and the United Kingdom; they are also used globally as a common binder for house paints. However, only a relatively limited number of heritage scientific studies have focused on vinyl paints. Consequently, many critical aspects of this material, such as the degradation processes, variations in paint formulations, and responses to conservation treatments, remain largely understudied. This article aims to summarise the available relevant information on poly(vinyl acetate) paints from both the scientific and the conservation practice perspectives. The article provides a brief overview of the development of poly(vinyl acetate) paints as artist-grade and household products and the known differences in their formulations. It also focuses on poly(vinyl acetate) ageing behaviour, the physicochemical properties, the recent scientific research on poly(vinyl acetate) material characterisation and degradation, and the main conservation issues regarding these paints, such as those relating to cleaning treatments.


Comparation of the outcomes between ProGlide based post-closure technique and arteriotomy repair for veno-arterial extracorporeal membrane oxygenation decannulation.
To compare outcomes between post-closure technique based on ProGlide and arteriotomy repair for veno-arterial extracorporeal membrane oxygenation (VA-ECMO) decannulation in this study. Patients who received VA-ECMO treatment and successfully removed from its support in Changhai Hospital from January 2018 to December 2021 were included in this study. Patients was divided into post-closure group and surgical repair group according to the artery access closure method used. Clinical data of these patients were retrospectively collected and analyzed. A total of 58 patients were eventually enrolled in this study, including 26 (44.83%) patients in post-closure group and 32 (55.17%) patients in surgical repair group. Post-closure group had shorter procedure time, less minor bleeding events, estimated blood loss and packed cells transfused compared with the surgical repair group. The intensive care unit (ICU) length of stay after decannulation and the hospital length of stay after ICU in post-closure group were both shorter than surgical repair group. Nine patients (15.52%) died of multiple system organ failure after decannulation in this cohort and there were no significant differences between two groups. Our study showed the post-closure technique based on ProGlide for VA-ECMO decannulation is feasible, safe and effective.


Efficacy of an oral angiotensin-converting enzyme inhibitor (captopril) in severe hypertension.
The antihypertensive effect of captopril was assessed during short- and long-term periods in ten patients with elevated blood pressure readings that were uncontrollable by standard therapy (supine diastolic blood pressure of greater than 100 mm Hg with a regimen of propranolol hydrochloride, hydralazine hydrochloride, and hydrochlorothiazide). When given alone, captopril therapy was unable to normalize the blood pressure in any patient. The addition of hydrochlorothiazide to the captopril therapy normalized the blood pressure in one patient and sharply improved the blood pressure in four others. The blood pressure in the remaining patients responded inadequately to this combination. The addition of propranolol to captopril and hydrochlorothiazide reduced the blood pressure further in most cases (seven on the ten patients had normal blood pressure readings while they received these three drugs). In four patients, the blood pressure response to the added propranolol was unrelated to changes in plasma angiotensin II concentration. Captopril was helpful in the management of refractory hypertension in most cases.


Self medication amongst general outpatients in a nigerian community hospital.
This study was designed to determine the proportion of general out patients who practice self medication, the drugs employed and the reasons for resorting to self medication. This study was conducted between June and December, 2007 at the General Outpatient Clinic of the Federal Medical Centre, Owo, Ondo State, Nigeria. Two hundred consenting respondents were selected by simple random sampling and interviewed with the aid of semi structured questionnaire by the authors with three assistants. Information regarding their bio-data, history of self medication, drugs used and the reasons for resorting to self medication were obtained. Majority of the respondents (85%) admitted to self medication while the remaining proportion (15%) did not practice it. Drugs utilized could be single, usually analgesics (26.5%) and anti-malaria (15.9%) or in combinations, usually antimalaria-analgesics (22.4%), antimalariaanalgesic- antibiotic (15.3%) and antibiotic-analgesic (10.0%). The reasons cited by respondents for self medication were their perception of their complaints been minor enough to be amenable to self medication (54.7%) and financial constraint (22.4%). Majority of the respondents practiced self medication using an array of drugs like analgesics, anti-malaria and antibiotics used either singly or in combination. The main reasons identified for self medication were that the ailments were minor and financial constraint.


A Comparison of the Average Sitting Pressures and Symmetry Indexes between Air-adjustable and Foam Cushions.
[Purpose] The purpose of this study was to determine the best adjustable cushions, for the maintenance of normal sitting balance by healthy persons in wheelchairs, from a foam cushion, and a newly-developed air-adjustable cushion. [Subjects] Eighteen healthy participants (9 men, 9 women) were recruited. [Methods] Participants were evaluated using the Force Sensing Array System to assess average sitting pressure and the symmetry index of chair sitting under the following conditions: no seat cushion, a foam cushion, and a newly-developed air-adjustable cushion. [Results] The results show that there were no significant differences among the average sitting pressures which were measured on the hard surface of a chair, a foam cushion, and the newly-developed cushion. The air-adjustable cushion's symmetry index turned out to be closer to 0 than those of the foam cushion and the hard surface of the chair. [Conclusion] We suggest that the newly-developed air-adjustable cushion contributes to a more symmetrical sitting posture than the basic foam cushion or no seat cushion.


Initiation and promotion of endochrondral bone formation by bone morphogenetic proteins: potential implications for avian tibial dyschondroplasia.
The initiation and promotion of bone morphogenesis is regulated by bone morphogenetic proteins. Morphogenesis of the skeleton is the developmental cascade of pattern formation, establishment of mirror-image bilateral symmetry, initiation and promotion of endochondral bone differentiation, and growth culminating in functional weight bearing. Implantation of demineralized bone matrix initiates a developmental cascade of endochondral bone formation that is reminiscent of the sequential bone morphogenesis in the limb bud in the embryo. The inductive agents in the demineralized bone matrix were identified, isolated and cloned, and demonstrated to be bone morphogenetic proteins (BMP). The BMP have been implicated in the pattern formation, differentiation, and regeneration of bone. Because there is a persistent defect in endochondral bone formation in the epiphysed growth plate in tibial dyschondroplasia in poultry, it is likely that BMP signaling mechanisms may be impaired.


Common variants of the thyroglobulin gene are associated with differentiated thyroid cancer risk.
Genetic factors are important in thyroid cancer susceptibility. Recently, it has been reported that there are associations of certain chromosome regions with thyroid cancer. In this case-control study, we sought to determine whether there is an association between differentiated thyroid cancer (DTC) and variants in regions of chromosome 8q. We used a case-control association design in a population of 877 individuals (398 patients with sporadic DTC and 479 healthy controls). The iPLEX technology was applied to analyze seven single-nucleotide polymorphisms (SNPs) in chromosome 8q: two SNPs that map at 8q24, previously reported as risk markers in different types of cancer, two SNPs in the thyrotropin-releasing hormone receptor gene (TRHR), and three SNPs in the thyroglobulin gene (TG). Risk assessment was done by unconditional regression analysis. The two SNPs that map at 8q24, rs6983267 and rs1447295, and the two TRHR polymorphisms showed no association with DTC. No association was also found for the exon 33 TG polymorphism. The two TG polymorphisms in the exon 10-12 cluster, however, were associated with an increased risk of DTC (dominant model odds ratio = 1.80, 95% confidence interval = 1.30-2.50, p < 0.001). In this study, we show for the first time that the TG gene is a susceptibility factor for thyroid cancer. Although these conclusions are based on a large population, additional studies are warranted to support these data.


Flame atomic absorption spectrometric determination of palladium in aqueous samples after preconcentration using nanoparticles of gamma-alumina functionalized with pyridine groups.
A new solid phase, nanoparticles of alumina functionalized with pyridine groups, was synthesized and used for extraction and preconcentration of palladium(II) ions from some water samples. The effects of various parameters such as pH, flow rates of sample and eluent, type and volume and concentration of eluent, sample volume, amount of adsorbent and cationic interferences have been studied and optimum conditions for best recovery have been obtained. The limit of detection of the method based on three times the standard deviation of the blank (3S(b)) was obtained: 0.6 ng mL(-1). The preconcentration factor and the adsorption capacity were also calculated to be 60 and 37 mg g(-1), respectively. The recovery of extraction of palladium ions on nano-alumina particles was determined to be 98.5%. The utility of the modified nano-alumina was tested in some samples and showed an RSD value of <0.8%, reflecting its accuracy and reproducibility.


Triennial Reproduction Symposium: deficiencies in the uterine environment and failure to support embryonic development.
Pregnancy failure in livestock can result from failure to fertilize the oocyte or embryonic loss during gestation. The focus of this review is on cattle and factors affecting and mechanisms related to uterine insufficiency for pregnancy. A variety of factors contribute to embryonic loss and it may be exacerbated in certain animals, such as high-producing lactating dairy cows, and in some cattle in which estrous synchronization and timed AI was performed, due to reduced concentrations of reproductive steroids. Recent research in beef cattle induced to ovulate immature follicles and in lactating dairy cows indicates that deficient uterine function is a major factor responsible for infertility in these animals. Failure to provide adequate concentrations of estradiol before ovulation results in prolonged effects on expression and localization of uterine genes and proteins that participate in regulating uterine functions during early gestation. Furthermore, progesterone concentrations during early gestation affect embryonic growth, interferon-tau production, and uterine function. Therefore, an inadequate uterine environment induced by insufficient steroid concentrations before and after ovulation could cause early embryonic death either by failing to provide an adequate uterine environment for recognition of embryo signaling, adhesion, and implantation or by failing to support appropriate embryonic growth, which could lead to decreased conceptus size and failed maternal recognition of pregnancy.


[The metrological support of medical laboratory activity].
The article discusses the methodological approaches in implementing of regulations of the Federal law FZ-102 "On the support of unity of measurements in the area of laboratory medicine "from the positions of GOSTK ISO 9001-2008 "The systems of quality management. Requirements" and GOST K ISO 15189-2009 "medical laboratories. The particular requirements to quality and competence". The application of GOSTK ISO 18113.1-5 "The medicine items for diagnostic in vitro. Information provided by manufacturer (marking)" neatly assigns the responsibility for support of metrological correctness of laboratory measurements.


Characterization and distribution of the hemagglutinins produced by Vibrio cholerae.
Examination of the distribution of cell-associated and soluble hemagglutinins (HA) produced by Vibrio cholerae revealed the existence of four different HAs. A cell-associated mannose-sensitive HA (MSHA) was produced only by the El Tor biotype. This was evident with all El Tor strains examined. It appears to be responsible for the HA biotyping differentiation of El Tor from classical biotype V. cholerae. The MSHA had no apparent divalent ion requirement; it was inhibited by D-mannose and D-fructose; and it was active on all human (A, B, O) and all chicken erythrocytes tested. Spontaneous MSHA- mutants of El Tor strains were selected by cosedimentation of MSHA+ parent bacteria with erythrocytes. An L-fucose-sensitive HA was detected transiently in early log-phase growth with two of the four classical strains examined and with MSHA- mutants of El Tor biotype strains 3083, 26-3, and 17. MSHA- mutants also expressed another cell-associated HA in late log-phase cultures. A "soluble" HA was detected in late log-phase cultures of all strains tested. This HA was not inhibitable by any sugars tested; it required CA2+ ions for maximum activity; and it was active on some chicken erythrocytes but not others.


Novel Disabled-1-expressing neurons identified in adult brain and spinal cord.
Components of the Reelin-signaling pathway are highly expressed in embryos and regulate neuronal positioning, whereas these molecules are expressed at low levels in adults and modulate synaptic plasticity. Reelin binds to Apolipoprotein E receptor 2 and Very-low-density lipoprotein receptors, triggers the phosphorylation of Disabled-1 (Dab1), and initiates downstream signaling. The expression of Dab1 marks neurons that potentially respond to Reelin, yet phosphorylated Dab1 is difficult to detect due to its rapid ubiquitination and degradation. Here we used adult mice with a lacZ gene inserted into the dab1 locus to first verify the coexpression of β-galactosidase (β-gal) in established Dab1-immunoreactive neurons and then identify novel Dab1-expressing neurons. Both cerebellar Purkinje cells and spinal sympathetic preganglionic neurons have coincident Dab1 protein and β-gal expression in dab1(lacZ/+) mice. Adult pyramidal neurons in cortical layers II-III and V are labeled with Dab1 and/or β-gal and are inverted in the dab1(lacZ/lacZ) neocortex, but not in the somatosensory barrel fields. Novel Dab1 expression was identified in GABAergic medial septum/diagonal band projection neurons, cerebellar Golgi interneurons, and small neurons in the deep cerebellar nuclei. Adult somatic motor neurons also express Dab1 and show ventromedial positioning errors in dab1-null mice. These findings suggest that: (i) Reelin regulates the somatosensory barrel cortex differently than other neocortical areas, (ii) most Dab1 medial septum/diagonal band neurons are probably GABAergic projection neurons, and (iii) positioning errors in adult mutant Dab1-labeled neurons vary from subtle to extensive.


[Ultrastructure of neuronal ceroid-lipofuscinoses].
The ultrastructure of autofluorescent residual bodies in the Jansky-Bielschowsky and Spielmeyer-Sjögren types of neuronal ceroid-lipofuscinoses (NCL) is variegated though the curvilinear profiles encompass the basic pattern. The infantile and Kufs' types are marked by granular cytosomes. Deposition of the lipopigments in NCL simulates the distribution of "wear and tear" lipofuscin enabling diagnosis by biopsy and electron microscopy in peripheral organs such as skin, rectum, and especially striated muscle. Pathological findings in the retina of the associated retinopathia pigmentosa entail typical NCL residual bodies in almost every type of retinal cells, a loss of photoreceptors, atrophy of pigment epithelial cells and displacement of melanin into inner layers of the retina. This retinopathia pigmentosa seems to be a regular finding of only the classic late infantile and juvenile human types of NCL since it is mostly absent in the adult human type and the canine NCL. As long as an enzyme deficiency of this autosomal recessive disorder remains unproven, the clinical diagnosis of NCL can only be morphologically confirmed by electron microscopy.


Efficacy and safety of donepezil in patients with Alzheimer's disease in assisted living facilities.
The aim of this 12-week, open-label study was to determine the safety and efficacy of donepezil in participants with Alzheimer's disease (AD) residing in assisted living facilities (ALFs). Participants received 5 mg donepezil daily for 6 weeks followed by 10 mg daily for 6 weeks. Primary and secondary outcomes were change from baseline in Mini-Mental State Examination (MMSE) and Neuropsychiatric Inventory 8 (NPI-8) scores, respectively. Safety was assessed by adverse events (AEs) and laboratory tests. Of the 97 participants, 76 completed the study. Mean MMSE score (18.7 at baseline) improved 1.8 points (P < .0001) at study end. Total NPI-8 score improved 1.8 points (P = .043). The most frequent AEs were nausea and diarrhea. Donepezil improved cognition and behavior and was safe and well tolerated. The results suggest a need for proactive screening and diagnosis of AD and support the value of treatment and use of donepezil in participants residing in ALFs.


The traits of "trait ecologists": An analysis of the use of trait and functional trait terminology.
Trait and functional trait approaches have revolutionized ecology improving our understanding of community assembly, species coexistence, and biodiversity loss. Focusing on traits promotes comparability across spatial and organizational scales, but terms must be used consistently. While several papers have offered definitions, it remains unclear how ecologists operationalize "trait" and "functional trait" terms. Here, we evaluate how researchers and the published literatures use these terms and explore differences among subdisciplines and study systems (taxa and biome). By conducting both a survey and a literature review, we test the hypothesis that ecologists' working definition of "trait" is adapted or altered when confronting the realities of collecting, analyzing and presenting data. From 486 survey responses and 712 reviewed papers, we identified inconsistencies in the understanding and use of terminology among researchers, but also limited inclusion of definitions within the published literature. Discrepancies were not explained by subdiscipline, system of study, or respondent characteristics, suggesting there could be an inconsistent understanding even among those working in related topics. Consistencies among survey responses included the use of morphological, phonological, and physiological traits. Previous studies have called for unification of terminology; yet, our study shows that proposed definitions are not consistently used or accepted. Sources of disagreement include trait heritability, defining and interpreting function, and dealing with organisms in which individuals are not clearly recognizable. We discuss and offer guidelines for overcoming these disagreements. The diversity of life on Earth means traits can represent different features that can be measured and reported in different ways, and thus, narrow definitions that work for one system will fail in others. We recommend ecologists embrace the breadth of biodiversity using a simplified definition of "trait" more consistent with its common use. Trait-based approaches will be most powerful if we accept that traits are at least as diverse as trait ecologists.


Luminescent ion pairs with tunable emission colors for light-emitting devices and electrochromic switches.
Most recently, stimuli-responsive luminescent materials have attracted increasing interest because they can exhibit tunable emissive properties which are sensitive to external physical stimuli, such as light, temperature, force, and electric field. Among these stimuli, electric field is an important external stimulus. However, examples of electrochromic luminescent materials that exhibit emission color change induced by an electric field are limited. Herein, we have proposed a new strategy to develop electrochromic luminescent materials based on luminescent ion pairs. Six tunable emissive ion pairs (IP1-IP6) based on iridium(iii) complexes have been designed and synthesized. The emission spectra of ion pairs (IPs) show concentration dependence and the energy transfer process is very efficient between positive and negative ions. Interestingly, IP6 displayed white emission at a certain concentration in solution or solid state. Thus, in this contribution, UV-chip (365 nm) excited light-emitting diodes showing orange, light yellow and white emission colors were successfully fabricated. Furthermore, IPs displayed tunable and reversible electrochromic luminescence. For example, upon applying a voltage of 3 V onto the electrodes, the emission color of the solution of IP1 near the anode or cathode changed from yellow to red or green, respectively. Color tunable electrochromic luminescence has also been realized by using other IPs. Finally, a solid-film electrochromic switch device with a sandwiched structure using IP1 has been fabricated successfully, which exhibited fast and reversible emission color change.


Struggling to be/show oneself valuable and worthy to get care. One aspect of the meaning of being dependent on care--a study of one patient, his wife and two of his professional nurses.
Dependency on care has commonly been described negatively and as a problem that needs to be addressed. From a larger data material, interviews with an old, hospitalized man with a chronic disease, his wife and two of his professional nurses was selected to study. The aim was to illuminate the meaning of being dependent on care, when it appears "negative". A phenomenological-hermeneutic approach was used to interpret the material. The interpretation shows that dependency on care is reluctantly shown although it is expected to be expressed and/or respected as it is shown. This makes dependency on care camouflaged and the space to be dependent is limited. The meaning of being dependent on care is understood as a two-dimensional struggle for existence. One dimension of the struggle is about to be/show oneself worthy to get care, as dependency on care holds a fear to be abandoned. The other dimension of the struggle is about to be/show oneself valuable as a human being, as identity is built upon being able to manage oneself and be strong. The interpretation if reflected on can open up possibilities to improve the quality of life for patients who are dependent on care.


Thymic and Bronchial Carcinoid Tumors in Multiple Endocrine Neoplasia Type 1: The Mayo Clinic Experience from 1977 to 2013.
The clinical features of thymic carcinoid (TC) and bronchial carcinoid (BC) tumors as part of multiple endocrine neoplasia type 1 (MEN1) have been rarely described and their importance in clinical practice is debated. The objective of this study was to describe the clinical presentation and outcome of this uncommon manifestation of MEN1 in a tertiary care center setting. We present the clinical features of patients with MEN1 and either TC or BC evaluated at the Mayo Clinic from 1977 to 2013. A total of 348 patients with MEN1 were evaluated and the prevalence of TC was 2.0% (n = 7) and of BC 4.9% (n = 17). The majority of the patients with BC were men (61%) diagnosed on routine screening (77%) and BC was not the confirmed cause of death in any patient. In contrast, TC patients were all men and during follow-up 43% died due to TC complications. We conclude that TC and BC tumors are uncommon, but important components of MEN1. BC were most commonly diagnosed during routine screening and associated with an indolent course. TC were predominantly seen in men and associated with a more aggressive behavior.


[Use of premapping of risks data sheet in artistic ceramics industries].
In 2006 there were more than 10,000 people working in artistic ceramics industries in Italy. The jobs in these industries that attracted most attention were work at the potter's wheel and decorating. To test the premapping of risks data sheet in these enterprises. We tested the data sheet in 3 craft industries: one was mainly artistic, one had a semi-industrial setting and in the third jobs were non-specific. In the semi-industrial craft industry the risks for potter's wheel workers were higher due to the repetitive movements required and to work organization aimed at achieving maximum productivity. The premapping of risks data sheet is a very sensitive tool. It can sometimes overestimate the risks, but in this way identifies situations that call for more in-depth analysis using tools that comply with international standards.


A phorbol ester that activates protein kinase C mimics the action of estradiol or epidermal growth factor for initiating embryo implantation in the delayed implanting hypophysectomized rat.
In rodents an action of estrogen is required for the initiation of implantation of the blastocyst into the endometrium of a progesterone-primed uterus. Thus removal of endogenous estrogen, either directly by ovariectomy or indirectly by hypophysectomy, prevents implantation in the pregnant rat. In the present study, delayed implanting hypophysectomized progesterone-primed rats were used to test the efficacy of cyclic adenosine 3',5'-monophosphate (cAMP), epidermal growth factor (EGF) and insulin-like growth factor-I (IGF-I), which are agents that have been shown to mimic some uterine actions of estradiol, to initiate implantation. In confirmation of previous studies, EGF injected into the uterine lumen plus intravenously was effective at initiating implantation in all animals. IGF-I showed no such activity in this model system. Cyclic AMP, increased via direct activation of adenylyl cyclase by forskolin, or administration of sodium dibutyryl cAMP, did not initiate implantation. However, a ligand for protein kinase C (PKC), phorbol 12-myristate 13-acetate, was effective in augmenting the action of intrauterine EGF, or forskolin, for initiation of implantation. A phorbol ester that does not activate PKC was ineffective. The results provide circumstantial evidence for the requirement of PKC activity in the implantation initiating action of estrogens.


A Study on the Properties of Carbon Black Mortar Using Granulated Blast Furnace Slag and Polymer.
White Portland Cement (WPC) and inorganic pigment have been used in colored concrete, but there are some physical problems such as increases in efflorescence, and poor workability and low economics. The aim of this study was to investigate the effects of GBFS and polymer (methyl cellulose) on the physical properties of carbon black mortar. For this purpose, a flow test, compressive strength test and color evaluation and was carried out on cement mortar mixed with polymer by changing the proportion of cement and ratio of GBFS. The results show that the addition of polymer influences significantly the color value efficiency in colored mortar. This is due to the reduction of overall amount of micro pore. This polymer films prevent the transport of soluble calcium towards the surface, and decreases efflorescence. And the flow of colored mortar was increased in proportion to the addition rate of the GBFS. In addition the strength of colored mortars with GBFS at the long-term aged (after 28 days) was higher than that of the general WPC mortar, although its strength was developed slowly at the early ages.


Model-based virtual patient analysis of human liver regeneration predicts critical perioperative factors controlling the dynamic mode of response to resection.
Liver has the unique ability to regenerate following injury, with a wide range of variability of the regenerative response across individuals. Existing computational models of the liver regeneration are largely tuned based on rodent data and hence it is not clear how well these models capture the dynamics of human liver regeneration. Recent availability of human liver volumetry time series data has enabled new opportunities to tune the computational models for human-relevant time scales, and to predict factors that can significantly alter the dynamics of liver regeneration following a resection. We utilized a mathematical model that integrates signaling mechanisms and cellular functional state transitions. We tuned the model parameters to match the time scale of human liver regeneration using an elastic net based regularization approach for identifying optimal parameter values. We initially examined the effect of each parameter individually on the response mode (normal, suppressed, failure) and extent of recovery to identify critical parameters. We employed phase plane analysis to compute the threshold of resection. We mapped the distribution of the response modes and threshold of resection in a virtual patient cohort generated in silico via simultaneous variations in two most critical parameters. Analysis of the responses to resection with individual parameter variations showed that the response mode and extent of recovery following resection were most sensitive to variations in two perioperative factors, metabolic load and cell death post partial hepatectomy. Phase plane analysis identified two steady states corresponding to recovery and failure, with a threshold of resection separating the two basins of attraction. The size of the basin of attraction for the recovery mode varied as a function of metabolic load and cell death sensitivity, leading to a change in the multiplicity of the system in response to changes in these two parameters. Our results suggest that the response mode and threshold of failure are critically dependent on the metabolic load and cell death sensitivity parameters that are likely to be patient-specific. Interventions that modulate these critical perioperative factors may be helpful to drive the liver regenerative response process towards a complete recovery mode.


Pleural electrophysiology variations according to location in pleural cavity.
The aim of the study was to compare the electrophysiology profile of sheep pleura originated from different locations of the pleural cavity with the respective profile in humans. Sheep specimens obtained from upper and lower lung lobes, 1st-4th and 8th-12th rib, ventral-dorsal diaphragm and mediastinum were mounted between Ussing chambers. Human visceral tissues were obtained from patients subjected to lobectomy. Trans-mesothelial resistance (R(TM)) was determined as an indicator of the tissue permeability, while amiloride and ouabain were used as inhibitors of cellular transportation via ion transporters. Control values R(TM) were low in lower lobe visceral, caudal costal parietal and diaphragmatic pleura. Amiloride increased R(TM) at all locations except upper visceral and mediastinum. Higher R(TM) increases were found in caudal parietal and dorsal diaphragmatic samples. Ouabain increased R(TM) of lower visceral, caudal parietal and diaphragmatic pleura but not of mediastinal specimens. Observations made in sheep tissue were comparable with human visceral, parietal and mediastinal regions. In conclusion, results suggest heterogeneity of trans-mesothelial permeability among different pleural locations in sheep as was the case for humans. Thoracic surgeons should consider physiology function of each part of pleural cavity before pleural tissue manipulation. Observations made in sheep may be used to understand human physiology.


Initial axillary surgery: results from the BreastSurgANZ Quality Audit.
The aim of this study was to establish the preference and reasons for initial axillary surgery performed on women with invasive breast cancer in Australia and New Zealand using data from the Breast Surgeon's Society of Australia and New Zealand Quality Audit (BQA) according to whether sentinel lymph node (SLN) biopsy, axillary lymph node dissection (ALND) or no axillary surgery was used. Patient data from 1999 to 2011 were categorized according to primary tumour size (≤3 cm or >3 cm) and analysed by year of diagnosis, type of initial axillary surgery and frequency of second axillary surgery following SLN biopsy. Patient age at diagnosis, health insurance status, surgeon caseload and hospital location were also examined as factors affecting the likelihood of performing different types of axillary surgery. Seventy thousand six hundred and eighty-eight episodes of early breast cancer with axillary surgery data were reported to the BQA in the study period. The proportion of patients undergoing SLN biopsy as the first operation increased over this period in both tumour size groups with a concomitant decline in the use of ALND as the first operation over the same interval. Elderly women (>70 years old) were four times less likely to undergo axillary surgery for their initial management when compared with women aged 41-70 years old (P < 0.001). Factors favouring ALND as the initial surgery over SLN biopsy included larger tumour size, elderly age, uninsured status and having surgery in a regional centre. From 1999 to 2011, SLN biopsy as the initial axillary surgery has been widely adopted by surgeons reporting to the BQA. Future evaluation of the BQA data in the following 3-5 years will be performed to monitor this progression.


Non-invasive cardiac output monitoring in preterm infants undergoing patent ductus arteriosus ligation: a comparison with echocardiography.
Non-invasive cardiac output monitoring (NICOM; NICOM™) may be useful in the management of extremely premature preterm infants. To evaluate a new bioreactance-based method of continuous NICOM in preterm infants following patent ductus arteriosus (PDA) ligation. Infants underwent three paired NICOM and echocardiography assessments of stroke volume (SV) and left ventricular output (LVO) in the postoperative period: at 1, 6-8, and 16-18 h postoperatively. NICOM- and echocardiography-measured SV and LVO during those periods were compared using Bland-Altman analysis and the intraclass correlation coefficient (ICC). Twenty-five infants with a median (interquartile range) gestational age and birth weight of 25.0 weeks (24.5-25.9) and 700 g (615-775), respectively, were included. The overall systematic bias (limits of agreement) across all time points between the NICOM and echocardiography SV readings was 39% (8-69) with NICOM consistently underestimating echocardiography values. There was moderate consistency between NICOM and echocardiography SV values (ICC 0.78, p < 0.001). Compared with the 1-hour scans, the 6- to 8- and 16- to 18-hour scans had increased biases of 7.9% (95% CI 2.5-13.2) and 9.7% (95% CI 3.6-15.8), respectively. Continuous LVO measurement using NICOM was feasible and demonstrated a consistent systematic bias compared with echocardiography in unstable extremely preterm infants without a PDA ligation. NICOM may be used as a trending tool for continuous monitoring in this population, but wide limits of agreement and increasing bias over time suggest it is not interchangeable with echocardiography. © 2014 S. Karger AG, Basel.


Isolation and characterization of Drosophila multidrug resistance gene homologs.
Mammalian multidrug-resistant cell lines, selected for resistance to a single cytotoxic agent, display cross-resistance to a broad spectrum of structurally and functionally unrelated compounds. These cell lines overproduce a membrane protein, the P-glycoprotein, which is encoded by a member(s) of a multigene family, termed mdr or pgp. The amino acid sequence of the P-glycoprotein predicts an energy-dependent transport protein with homology to a large superfamily of proteins which transport a wide variety of substances. This report describes the isolation and characterization of two Drosophila homologs of the mammalian mdr gene. These homologs, located in chromosomal sections 49EF and 65A, encode proteins that share over 40% amino acid identity to the human and murine mdr P-glycoproteins. Fly strains bearing disruptions in the homolog in section 49EF have been constructed and implicate this gene in conferring colchicine resistance to the organism. This work sets the foundation for the molecular and genetic analysis of mdr homologs in Drosophila melanogaster.


[Cerebral ischemia-hypoxia and biophysical mechanisms of neurodegeneration and neuroprotection effects].
Neuronal responses to hypoxia-ischemia can be acute or chronic. In the early stages neuronal responses to ischemia-hypoxia are dependent on the modulation of ion channels. Acute responses relay mainly on O2-regulated ion channels which mediate adaptive changes in neuron excitability. Energy failure, an early consequence of hypoxia-ischemia, causes disruption of ionic homeostasis and accumulation of extracellular neurotransmitters. NMDA and AMPA/kainate receptors and Ca2+ channels contribute to excitotoxic neuronal degeneration. Excitotoxicity leads to increased Ca2+ influx, which can activate cytotoxic intracellular pathways. Reactive oxygen species (oxygen free radicals) generated during ischemia-reperfusion contribute to the injury. Oxygen free-radicals serve as important signalling molecules that trigger inflammation and apoptosis. Excitatory amino acid-receptor antagonists and Ca2+ channels blockers can provide neuroprotection in experimental models of hypoxia-ischemia but disrupt normal brain function. Because of their relative lack of behavioral side-effects, voltage-dependent Na+ channels blockers may have advantage over other neuroprotective mechanisms. The blockade of voltage-gated Na+ channels reduces the excitability of neurons, Na+ influx and the accumulation of intracellular Na+. These improve the ionic homeostasis and cellular energy levels and prevent ischemia-hypoxia induced neuronal injury and neuronal damage mediated by Ca2+ overload.


Perceived sources of stress and resilience in men in an African American community.
Little is known about the perceived causes of stress and what strategies African American men use to promote resiliency. Participatory research approaches are recommended as an approach to engage minority communities. A key goal of participatory research is to shift the locus of control to community partners. To understand perceived sources of stress and tools used to promote resiliency in African American men in South Los Angeles. Our study utilized a community-partnered participatory research approach to collect and analyze open-ended responses from 295 African American men recruited at a local, cultural festival in Los Angeles using thematic analysis and the Levels of Racism framework. Almost all men (93.2%) reported stress. Of those reporting stress, 60.8% reported finances and money and 43.2% reported racism as a specific cause. More than 60% (63.4%) reported that they perceived available sources of help to deal with stress. Of those noting a specific source of help for stress (n = 76), 42.1% identified religious faith. Almost all of participants (92.1%) mentioned specific sources of resiliency such as religion and family. Stress owing to psychosocial factors such as finances and racism are common among African American men. But, at the same time, most men found support for resiliency to ameliorate stress in religion and family. Future work to engage African American men around alleviating stress and supporting resiliency should both take into account the perceived causes of stress and incorporate culturally appropriate sources of resiliency support.


Isotopic immunoglobulin: a new systemic therapy for advanced Hodgkin's disease.
Thirty-eight patients with advanced, progressive Hodgkin's disease who had relapsed from or who had not responded to treatment with at least two potentially curative combination chemotherapy regimens were entered into this phase 2 study. All patients received 131I antiferritin antibody administered intravenously (IV) at a dose of 30 mCi on day 0 and 20 mCi on day 5. Antibody was derived from rabbit, pig, and monkey species. Objective partial remission of measurable disease was recorded in 40% of patients. Symptomatic response was recorded in 77% of patients. Toxicity was restricted to bone marrow depression with thrombocytopenia greater than leukopenia. These responses are comparable to other reported phase 2 drugs in this patient population and subsequent trials of antibody free of radioactivity and antibody using a beta emitting isotope are being carried out to expand upon these results.


Comparison of neural network predictors in the classification of tracheal-bronchial breath sounds by respiratory auscultation.
Despite extensive research in the area of identification and discrimination of tracheal-bronchial breath sounds by computer analysis, the process of identifying auscultated sounds is still subject to high estimation uncertainties. Here we assess the performance of the relatively new constructive probabilistic neural network (CPNN) against the more common classifiers, namely the multilayer perceptron (MLP) and radial basis function network (RBFN), in classifying a broad range of tracheal-bronchial breath sounds. We present our data as signal estimation models of the tracheal-bronchial frequency spectra. We have examined the trained structure of the CPNN with respect to the other architectures and conclude that this architecture offers an attractive means with which to analyse this type of data. This is based partly on the classification accuracies attained by the CPNN, MLP and RBFN which were 97.8, 77.8 and 96.2%, respectively. We concluded that CPNN and RBFN networks are capable of working successfully with this data, with these architectures being acceptable in terms of topological size and computational overhead requirements. We further believe that the CPNN is an attractive classification mechanism for auscultated data analysis due to its optimal data model generation properties and computationally lightweight architecture.


Distinct expression patterns of ICK/MAK/MOK protein kinases in the intestine implicate functional diversity.
ICK/MRK (intestinal cell kinase/MAK-related kinase), MAK (male germ cell-associated kinase), and MOK (MAPK/MAK/MRK-overlapping kinase) are closely related serine/threonine protein kinases in the protein kinome. The biological functions and regulatory mechanisms of the ICK/MAK/MOK family are still largely elusive. Despite significant similarities in their catalytic domains, they diverge markedly in the sequence and structural organization of their C-terminal non-catalytic domains, raising the question as to whether they have distinct, overlapping, or redundant biological functions. In order to gain insights into their biological activities and lay a fundamental groundwork for functional studies, we investigated the spatio-temporal distribution patterns and the expression dynamics of ICK/MAK/MOK protein kinases in the intestine. We found that ICK/MAK/MOK proteins display divergent expression patterns along the duodenum-to-colon axis and during postnatal murine development. Furthermore, they are differentially partitioned between intestinal epithelium and mesenchyme. A significant increase in the protein level of ICK, but not MAK, was induced in human primary colon cancer specimens. ICK protein level was up-regulated whereas MOK protein level was down-regulated in mouse intestinal adenomas as compared with their adjacent normal intestinal mucosa. These data suggest distinct roles for ICK/MAK/MOK protein kinases in the regulation of intestinal neoplasia. Taken together, our findings demonstrate that the expressions of ICK/MAK/MOK proteins in the intestinal tract can be differentially and dynamically regulated, implicating a significant functional diversity within this group of protein kinases.


Exploring the active site binding specificity of kallikrein-related peptidase 5 (KLK5) guides the design of new peptide substrates and inhibitors.
Kallikrein-related peptidase 5 (KLK5) is a promising therapeutic target in several skin diseases, including Netherton syndrome, and is emerging as a potential target in various cancers. In this study, we used a sparse matrix library of 125 individually synthesized peptide substrates to characterize the binding specificity of KLK5. The sequences most favored by KLK5 were GRSR, YRSR and GRNR, and we identified sequence-specific interactions involving the peptide N-terminus by analyzing kinetic constants (kcat and KM) and performing molecular dynamics simulations. KLK5 inhibitors were subsequently engineered by substituting substrate sequences into the binding loop (P1, P2 and P4 residues) of sunflower trypsin inhibitor-1 (SFTI-1). These inhibitors were effective against KLK5 but showed limited selectivity, and performing a further substitution at P2' led to the design of a new variant that displayed improved activity against KLK5 (Ki=4.2±0.2 nm), weak activity against KLK7 and 12-fold selectivity over KLK14. Collectively, these findings provide new insight into the design of highly favored binding sequences for KLK5 and reveal several opportunities for modulating inhibitor selectivity over closely related proteases that will be useful for future studies aiming to develop therapeutic molecules targeting KLK5.


Microbe Profile: Thermococcus kodakarensis: the model hyperthermophilic archaeon.
Thermococcus kodakarensis is a hyperthermophilic Euryarchaeon that grows well under laboratory conditions and, being naturally competent for genetic transformation, it has become a widely studied experimental model species. With the genome sequence available since 2004, combining genetic, enzymological and structural biochemical approaches has revealed previously unknown and unanticipated features of archaeal molecular biology and metabolism. T. kodakarensis DNA polymerase is already commercialized and with the details of metabolism and hydrogenase available, generating H2 from biopolymers solubilized at high temperatures, most notably chitin, now seems a very attractive possibility as a renewable energy bioprocess.


Evidence does not support absorption of intact solid lipid nanoparticles via oral delivery.
Whether and to what extent solid lipid nanoparticles (SLNs) can be absorbed integrally via oral delivery should be clarified because it is the basis for elucidation of absorption mechanisms. To address this topic, the in vivo fate of SLNs as well as their interaction with biomembranes is investigated using water-quenching fluorescent probes that can signal structural variations of lipid-based nanocarriers. Live imaging indicates prolonged retention of SLNs in the stomach, whereas in the intestine, SLNs can be digested quickly. No translocation of intact SLNs to other organs or tissues can be observed. The in situ perfusion study shows bioadhesion of both SLNs and simulated mixed micelles (SMMs) to intestinal mucus, but no evidence of penetration of integral nanocarriers. Both SLNs and SMMs exhibit significant cellular uptake, but fail to penetrate cell monolayers. Confocal laser scanning microscopy reveals that nanocarriers mainly concentrate on the surface of the monolayers, and no evidence of penetration of intact vehicles can be obtained. The mucous layer acts as a barrier to the penetration of both SLNs and SMMs. Both bile salt-decoration and SMM formulation help to strengthen the interaction with biomembranes. It is concluded that evidence does not support absorption of intact SLNs via oral delivery.


Assessment of faculty productivity in academic departments of medicine in the United States: a national survey.
Faculty productivity is essential for academic medical centers striving to achieve excellence and national recognition. The objective of this study was to evaluate whether and how academic Departments of Medicine in the United States measure faculty productivity for the purpose of salary compensation. We surveyed the Chairs of academic Departments of Medicine in the United States in 2012. We sent a paper-based questionnaire along with a personalized invitation letter by postal mail. For non-responders, we sent reminder letters, then called them and faxed them the questionnaire. The questionnaire included 8 questions with 23 tabulated close-ended items about the types of productivity measured (clinical, research, teaching, administrative) and the measurement strategies used. We conducted descriptive analyses. Chairs of 78 of 152 eligible departments responded to the survey (51% response rate). Overall, 82% of respondents reported measuring at least one type of faculty productivity for the purpose of salary compensation. Amongst those measuring faculty productivity, types measured were: clinical (98%), research (61%), teaching (62%), and administrative (64%). Percentages of respondents who reported the use of standardized measurements units (e.g., Relative Value Units (RVUs)) varied from 17% for administrative productivity to 95% for research productivity. Departments reported a wide variation of what exact activities are measured and how they are monetarily compensated. Most compensation plans take into account academic rank (77%). The majority of compensation plans are in the form of a bonus on top of a fixed salary (66%) and/or an adjustment of salary based on previous period productivity (55%). Our survey suggests that most academic Departments of Medicine in the United States measure faculty productivity and convert it into standardized units for the purpose of salary compensation. The exact activities that are measured and how they are monetarily compensated varied substantially across departments.


ATM and DNA-PK function redundantly to phosphorylate H2AX after exposure to ionizing radiation.
H2AX phosphorylation is an early step in the response to DNA damage. It is widely accepted that ATM (ataxia telangiectasia mutated protein) phosphorylates H2AX in response to DNA double-strand breaks (DSBs). Whether DNA-dependent protein kinase (DNA-PK) plays any role in this response is unclear. Here, we show that H2AX phosphorylation after exposure to ionizing radiation (IR) occurs to similar extents in human fibroblasts and in mouse embryo fibroblasts lacking either DNA-PK or ATM but is ablated in ATM-deficient cells treated with LY294002, a drug that specifically inhibits DNA-PK. Additionally, we show that inactivation of both DNA-PK and ATM is required to ablate IR-induced H2AX phosphorylation in chicken cells. We confirm that H2AX phosphorylation induced by DSBs in nonreplicating cells is ATR (ataxia telangiectasia and Rad3-related protein) independent. Taken together, we conclude that under most normal growth conditions, IR-induced H2AX phosphorylation can be carried out by ATM and DNA-PK in a redundant, overlapping manner. In contrast, DNA-PK cannot phosphorylate other proteins involved in the checkpoint response, including chromatin-associated Rad17. However, by phosphorylating H2AX, DNA-PK can contribute to the presence of the damage response proteins MDC1 and 53BP1 at the site of the DSB.


Determining the sensitivity of computed tomography scanning in early detection of subarachnoid hemorrhage.
This study aims to determine the sensitivity of modern computed tomography (CT) scanners in detecting subarachnoid hemorrhage (SAH) and to determine whether there is a continued need for lumbar puncture to exclude the diagnosis. This retrospective study was conducted from January 2000 to December 2005. The study population consisted of all patients referred on suspicion of SAH or with verified SAH. All medical records were reviewed together with results from CT scan, angiography, and cerebral spinal fluid analysis. Clinical history, examination findings, and time from onset of symptoms until CT scan (days) were recorded. Patients with a negative CT scan had a lumbar puncture done. A total of 499 patients were included. In 203 patients the diagnosis was excluded by a negative CT scan and negative lumbar puncture. Two hundred ninety-six patients were found to have a SAH. The diagnosis in 295 of these patients was based on a positive CT scan. In a single patient, on day 6, the diagnosis was based on a positive lumbar puncture. From day 1 to day 5, CT scanning was found to have a sensitivity of 100%. Overall, CT scanning had a sensitivity of 99.7 % (95% confidence interval: 98.1-99.99%). CT scanning is excellent for diagnosing SAH. We demonstrate that in the first days after ictus a negative CT scan is sufficient to exclude SAH. Data do not allow for any specific cutoff point to be made. We suggest leaving out lumbar puncture in the first 3 days after ictus if the results of the CT scan are negative.


Renal physiology series: Part 5b of 8. Renal control of phosphorus and magnesium.
The kidney plays a major role in the maintenance of phosphorus and magnesium balance. The homeostasis of these substances is complex and also involves the gastrointestinal tract and the bone. This article reviews the functions, homeostasis, and renal handling and regulation of phosphorus and magnesium. The major sites of tubular reabsorption and the presumed cellular mechanisms involved are described.


Insights in spatio-temporal characterization of human fetal neural stem cells.
Primary human fetal cells have been used in clinical trials of cell replacement therapy for the treatment of neurodegenerative disorders such as Huntington's disease (HD). However, human fetal primary cells are scarce and difficult to work with and so a renewable source of cells is sought. Human fetal neural stem cells (hfNSCs) can be generated from human fetal tissue, but little is known about the differences between hfNSCs obtained from different developmental stages and brain areas. In the present work we characterized hfNSCs, grown as neurospheres, obtained from three developmental stages: 4-5, 6-7 and 8-9weeks post conception (wpc) and four brain areas: forebrain, cortex, whole ganglionic eminence (WGE) and cerebellum. We observed that, as fetal brain development proceeds, the number of neural precursors is diminished and post-mitotic cells are increased. In turn, primary cells obtained from older embryos are more sensitive to the dissociation process, their viability is diminished and they present lower proliferation ratios compared to younger embryos. However, independently of the developmental stage of derivation proliferation ratios were very low in all cases. Improvements in the expansion rates were achieved by mechanical, instead of enzymatic, dissociation of neurospheres but not by changes in the seeding densities. Regardless of the developmental stage, neurosphere cultures presented large variability in the viability and proliferation rates during the initial 3-4 passages, but stabilized achieving significant expansion rates at passage 5 to 6. This was true also for all brain regions except cerebellar derived cultures that did not expand. Interestingly, the brain region of hfNSC derivation influences the expansion potential, being forebrain, cortex and WGE derived cells the most expandable compared to cerebellar. Short term expansion partially compromised the regional identity of cortical but not WGE cultures. Nevertheless, both expanded cultures were multipotent and kept the ability to differentiate to region specific mature neuronal phenotypes.


Successful implementation of a novel internet hybrid surgery curriculum: the early phase outcome of thoracic surgery prerequisite curriculum e-learning project.
The internet CD-ROM thoracic surgery (TS) e-learning system was implemented in 2001 as a prospective randomized trial testing resident acceptance and educational impact of a unique web-based curriculum system on prematriculated TS residents. The Prerequisite Curriculum (PRC) contains 75 segments organized with textbook and case-based navigational systems. Web-based technology tracked the PRC use for each resident. Of 142 residents, 138 thoracic surgery residents matching in 2001 for 2002 matriculation participated in a prospective randomized trial comparing the PRC system to a control group. Two sets of in-training exams, as well as resident and faculty knowledge/performance surveys, were used from July 2001 through January 2004 for ongoing, blinded multidimensional evaluation. Most residents (55/69) responded to the written prematriculation surveys and indicated they used the PRC (43/55), averaging 1.45 hours weekly. The PRC was rated as easy to use (8.3/10), a valuable study guide (7.7/10), and superior to traditional texts and journals for preresidency preparation (7.9/10). Web-based tracking revealed that 47/69 actually used the PRC. Sessions averaged 23.3 minutes with an average of 148 sessions over the prematriculation year. The in-training exam performance when evaluated at 1 and 9 months into the TS residency revealed a positive correlation between examination performance and PRC use. After TS residency matriculation, the self-evaluated knowledge and performance satisfaction scores were superior among PRC users in all categories. Simultaneous TS faculty evaluations of the same resident groups demonstrated smaller, but significant group differences. The implementation of the TS PRC has been exciting and successful. Future multidisciplinary curricular progress will hopefully continue to build upon this e-learning strategy.


Comparison of combination methods to create calibrated ensemble forecasts for seasonal influenza in the U.S.
The characteristics of influenza seasons vary substantially from year to year, posing challenges for public health preparation and response. Influenza forecasting is used to inform seasonal outbreak response, which can in turn potentially reduce the impact of an epidemic. The United States Centers for Disease Control and Prevention, in collaboration with external researchers, has run an annual prospective influenza forecasting exercise, known as the FluSight challenge. Uniting theoretical results from the forecasting literature with domain-specific forecasts from influenza outbreaks, we applied parametric forecast combination methods that simultaneously optimize model weights and calibrate the ensemble via a beta transformation and made adjustments to the methods to reduce their complexity. We used the beta-transformed linear pool, the finite beta mixture model, and their equal weight adaptations to produce ensemble forecasts retrospectively for the 2016/2017, 2017/2018, and 2018/2019 influenza seasons in the U.S. We compared their performance to methods that were used in the FluSight challenge to produce the FluSight Network ensemble, namely the equally weighted linear pool and the linear pool. Ensemble forecasts produced from methods with a beta transformation were shown to outperform those from the equally weighted linear pool and the linear pool for all week-ahead targets across in the test seasons based on average log scores. We observed improvements in overall accuracy despite the beta-transformed linear pool or beta mixture methods' modest under-prediction across all targets and seasons. Combination techniques that explicitly adjust for known calibration issues in linear pooling should be considered to improve probabilistic scores in outbreak settings.


Cost-effectiveness of iodixanol in patients at high risk of contrast-induced nephropathy.
Acute renal failure after contrast-induced nephropathy is a clinically important and costly complication after the use of iodine-based contrast media. We investigated the cost and cost-effectiveness of 2 contrast media in patients at high risk of contrast-induced nephropathy. The analyses were based on a randomized, prospective, multinational clinical study comparing the nephrotoxic effects of an isosmolar nonionic contrast medium, iodixanol, with those of a low-osmolar nonionic contrast medium, iohexol. Resource utilization data were obtained from the study and from a retrospective review of patients' hospital records. Swedish, German, and French unit prices were applied to resources used. Between-group differences in average costs were analyzed using a nonparametric bootstrap method. Resource utilization data for 125 patients were analyzed. Seven contrast media-related serious adverse reactions, of which 6 were acute renal failures, were noted in 6 patients receiving iohexol. Two patients in the iodixanol group had 1 nonserious reaction each. The mean hospitalization cost per patient was Euros 489, Euros 573, and Euros 393 lower after iodixanol than after iohexol using Swedish, German, and French unit prices, respectively. The mean per-patient costs of treating adverse drug reactions were Euros 371, Euros 399, and Euros 445 lower after iodixanol than after iohexol, using the respective unit prices (P < or = 0.01). Iodixanol was cost-effective compared with iohexol, with both lower costs and better effects related to fewer adverse drug reactions. The isosmolar contrast medium iodixanol appears to be cost-effective when compared with a low-osmolar contrast medium, iohexol, in diabetic patients with renal impairment undergoing angiography.


Projections from the superior olive and lateral lemniscus to tonotopic regions of the rat's inferior colliculus.
The projections to physiologically defined tonotopic regions of the central nucleus of the inferior colliculus (ICC) from the adult rat's superior olivary complex (SOC) and lateral lemniscus were investigated using retrograde tract tracing methods. Iontophoretic injections of the retrograde tracers, Fluoro-Gold (FG) or horseradish peroxidase (HRP), were made into the ICC through a glass micropipette, which also served as a recording electrode to determine the frequency response at the injection site. Injections were made into frequency-specific regions based on the best responses of neurons to contralaterally presented tones between 2 25 kHz. In the dorsal nucleus of the lateral lemniscus (DNLL) neurons were labeled both ipsilaterally and contralaterally to the injection site with a larger proportion projecting to the contralateral side. The distribution of labeled cells was concentric, with high frequencies represented along the outer margin and low frequencies represented centrally within DNLL. The lateral superior olive (LSO) was labeled bilaterally, with high frequencies represented medially and low frequencies laterally along the nuclear axis. The projection from the medial superior olive (MSO) was ipsilateral, with high frequencies represented ventrally and low frequencies dorsally. The projection from the superior paraolivary nucleus (SPN) was also largely ipsilateral, with high frequencies represented medially and low frequencies laterally. The intermediate and ventral nuclei of the lateral lemniscus (INLL and VNLL) were also labeled ipsilaterally and exhibited a distribution of tracer that depended on the frequency of the injection site: the low frequency projection was banded but the high frequency projection was more evenly distributed.


Life history adaptations to fluctuating environments: Combined effects of demographic buffering and lability.
Demographic buffering and lability have been identified as adaptive strategies to optimise fitness in a fluctuating environment. These are not mutually exclusive, however, we lack efficient methods to measure their relative importance for a given life history. Here, we decompose the stochastic growth rate (fitness) into components arising from nonlinear responses and variance-covariance of demographic parameters to an environmental driver, which allows studying joint effects of buffering and lability. We apply this decomposition for 154 animal matrix population models under different scenarios to explore how these main fitness components vary across life histories. Faster-living species appear more responsive to environmental fluctuations, either positively or negatively. They have the highest potential for strong adaptive demographic lability, while demographic buffering is a main strategy in slow-living species. Our decomposition provides a comprehensive framework to study how organisms adapt to variability through buffering and lability, and to predict species responses to climate change.


Long-term hypotensive effect of beta-agonist in conscious dogs.
The purpose of this study was to investigate the arterial pressure response to long-term administration of beta-agonists in the chronically instrumented conscious animal model. Chronically instrumented dogs were given intravenous infusions of ritodrine (2 micrograms.kg-1.min-1) for a period of 2 wk. Several cardiovascular and renal parameters were monitored before, during, and after the ritodrine infusion, and renal function curves were constructed. After the 1st wk of infusion, a new steady state was reestablished, and this was characterized by hypotension, reduced plasma protein concentration, elevated cardiac output, expanded extracellular fluid space, and near normal levels of activity of renin-angiotensin-aldosterone systems. The renal function curve during ritodrine infusion shifted to the left with no change in slope. We propose the following: 1) the persistence of hypotension is most probably related to the resetting of the arterial pressure-kidney blood volume servocontrol mechanisms, and 2) the persistent elevation of cardiac output and reduction in peripheral resistance are most probably related to increased oxygen and nutrient demand during beta-agonist infusions.


Analysis of human bradykinin receptor gene and endothelial nitric oxide synthase gene polymorphisms in end-stage renal disease among malaysians.
The aim of this study was to determine the association of the c.894G>T; p.Glu298Asp polymorphism and the variable number tandem repeat (VNTR) polymorphism of the endothelial nitric oxide synthase (eNOS) gene and c.181C>T polymorphism of the bradykinin type 2 receptor gene (B2R) in Malaysian end-stage renal disease (ESRD) subjects. A total of 150 ESRD patients were recruited from the National Kidney Foundation's (NKF)dialysis centers in Malaysia and compared with 150 normal healthy individuals. Genomic DNA was extracted from buccal cells of all the subjects. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was carried out to amplify the products and the restricted fragments were separated by agarose gel electrophoresis. Statistical analyses were carried out using software where a level of p <0.05 was considered to be statistically significant. The genotypic and allelic frequencies of the B2R gene (c.181C>T, 4b/a) and eNOS gene (c.894G>T) polymorphisms were not statistically significant (p >0.05) when compared to the control subjects. The B2R and eNOS gene polymorphisms may not be considered as genetic susceptibility markers for Malaysian ESRD subjects.


Societal and economic impact of anterior cruciate ligament tears.
An anterior cruciate ligament (ACL) tear is a common knee injury, particularly among young and active individuals. Little is known, however, about the societal impacts of ACL tears, which could be large given the typical patient age and increased lifetime risk of knee osteoarthritis. This study evaluates the cost-effectiveness of ACL reconstruction compared with structured rehabilitation only. A cost-utility analysis of ACL reconstruction compared with structured rehabilitation only was conducted with use of a Markov decision model over two time horizons: the short to intermediate term (six years), on the basis of Level-I evidence derived from the KANON Study and the Multicenter Orthopaedic Outcomes Network (MOON) database; and the lifetime, on the basis of a comprehensive literature review. Utilities were assessed with use of the SF-6D. Costs (in 2012 U.S. dollars) were estimated from the societal perspective and included the effects of the ACL tear on work status, earnings, and disability. Effectiveness was expressed as quality-adjusted life years (QALYs) gained. In the short to intermediate term, ACL reconstruction was both less costly (a cost reduction of $4503) and more effective (a QALY gain of 0.18) compared with rehabilitation. In the long term, the mean lifetime cost to society for a typical patient undergoing ACL reconstruction was $38,121 compared with $88,538 for rehabilitation. ACL reconstruction resulted in a mean incremental cost savings of $50,417 while providing an incremental QALY gain of 0.72 compared with rehabilitation. Effectiveness gains were driven by the higher probability of an unstable knee and associated lower utility in the rehabilitation group. Results were most sensitive to the rate of knee instability after initial rehabilitation. ACL reconstruction is the preferred cost-effective treatment strategy for ACL tears and yields reduced societal costs relative to rehabilitation once indirect cost factors, such as work status and earnings, are considered. The cost of an ACL tear over the lifetime of a patient is substantial, and resources should be directed to developing innovations for injury prevention and for altering the natural history of an ACL injury.


Open hardware in microscopy.
The field of microscopy has been empowering humankind for many centuries by enabling the observation of objects that are otherwise too small to detect for the naked human eye. Microscopy techniques can be loosely divided into three main branches, namely photon-based optical microscopy, electron microscopy, and scanning probe microscopy with optical microscopy being the most prominent one. On the high-end level, optical microscopy nowadays enables nanometer resolution covering many scientific disciplines ranging from material sciences over the natural sciences and life sciences to the food sciences. On the lower-end level, simplified hardware and openly available description and blueprints have helped to make powerful microscopes widely available to interested scientists and researchers. For this special issue, we invited contributions from the community to share their latest ideas, designs, and research results on open-source hardware in microscopy. With this collection of articles, we hope to inspire the community to further increase the accessibility, interoperability, and reproducibility of microscopy. We further touch on the standardization of methodologies and devices including the use of computerized control of data acquisition and data analysis to achieve high quality and efficiency in research and development.


Immunochemical and functional studies of Actinomyces viscosus T14V type 1 fimbriae with monoclonal and polyclonal antibodies directed against the fimbrial subunit.
Each of five monoclonal antibodies (mAbs) prepared against the type 1 fimbriae of Actinomyces viscosus T14V reacted with a 54 kDa cloned protein previously identified as a fimbrial subunit. This purified protein completely inhibited the reaction of a specific anti-type-1-fimbria rabbit antibody with A. viscosus whole cells. Maximum values for the number of antibody molecules bound per bacterial cell ranged from 7 x 10(3) to 1.2 x 10(4) for the different 125I-labelled mAbs and was approximately 7 x 10(4) for 125I-labelled rabbit IgG or Fab against either type 1 fimbriae or the 54 kDa cloned protein. Although the different mAbs, either individually or as a mixture, failed to inhibit the type-1-fimbria-mediated adherence of A. viscosus T14V to saliva-treated hydroxyapatite, each rabbit antibody gave 50% inhibition of adherence when approximately 5 x 10(4) molecules of IgG were bound per cell. However, binding of each corresponding rabbit Fab had no significant effect on bacterial attachment unless much higher concentrations were used. These findings suggest that antibodies directed solely against the 54 kDa fimbrial subunit do not react with the putative receptor binding sites of A. viscosus T14V type 1 fimbriae. Instead, inhibition of attachment by the polyclonal antibodies may depend on an indirect effect of antibody binding that prevents the fimbria-receptor interaction.


[Protecting effects of m-nifedipine on isoproterenol-induced myocardial injury in rats].
To test whether m-nifedipine (m-Nif) protects heart against myocardial injury induced by a single subcutaneous injection of isoproterenol (Iso) 30 mg/kg, male rats were injected subcutaneously twice daily with m-Nif 6 mumols/kg for 4 d. Hemodynamic changes, serum creatine kinase activity and ion contents of myocardial tissue and mitochondria were assessed about 6 h after Iso injection. While it did not notably influence blood pressure, heart rate and left ventricular contracting function of rats, m-Nif markedly attenuated calcium accumulation in myocardial tissue and mitochondria, reduced magnesium and potassium loss in myocardial tissue, depressed the release of creatine kinase and prevented the elevation of left ventricular end diastolic pressure. These beneficial effects of m-Nif were similar to those of nifedipine (Nif). However, m-Nif decreased minute tension-time index more significantly than the same dose of Nif. It is possible that m-Nif protects the rat heart from isoproterenol-induced injury by inhibiting transsarcolemmal calcium influx.


Portable Pesticide Electrochem-sensor: A Label-Free Detection of Glyphosate in Human Urine.
The toxicity levels of and exposure to glyphosate, a widely used herbicide and desiccant, are significant public health issues. In this study, we aim to design a highly sensitive, label-free, portable sensor for the direct detection of glyphosate in human urine. The sensor platform consists of a portable, printed circuit board circular platform with gold working and reference electrodes to enable nonfaradic electrochemical impedance spectroscopy. The sensing platform was an immunoassay-based, gold electrode surface immobilized with a monolayer of dithiobis(succinimidyl propionate) (DSP), a thiol-based cross-linker, which was then modified with a glyphosate antibody (Glyp-Ab) through the bonding of the ester group of DSP with the amide of the antibody (Glyp-Ab). The sensor was tested electrochemically, first using the laboratory-based benchtop method for the glyphosate-spiked urine samples, resulting in a dynamic response in the concentration range of 0.1-72 ng/mL with a limit of detection of 0.1 ng/mL. The platform showed high selectivity in the presence of major interfering analytes in urine [malathion (Mal), 3-phenoxybenzoic acid (PBA), and chlorpyrifos (Chlp)] and high reproducibility. The sensing platform was then translated into a portable device that showed a performance correlation (r = 0.994) with the benchtop (laboratory method). This developed portable sensing approach can be a highly reliable alternate sensor platform for the direct detection of pesticides in human bodily fluids.


Fangchinoline Promotes Autophagy and Inhibits Apoptosis in Osteoporotic Rats.
BACKGROUND Osteoporosis is a common disorder leading to bone loss. At present, the treatment options available for the management of osteoporosis are limited. The present investigation evaluated the protective effect of fangchinoline against osteoporosis and also postulates the possible mechanism of action. MATERIAL AND METHODS Osteoporosis was induced by subcutaneously injecting prednisolone (2.5 mg/pellet) for 4 weeks. Fangchinoline 1, 3 and 10 mg/kg was given intraperitoneally for the period. Protective effects of fangchinoline were assessed by estimating microarchitectural parameters and bone mineral density (BMD) in the vertebrae tissues, and biochemical parameters were also determined in the serum of rats with prednisolone-induced osteoporosis. Moreover, gene expression of microtubule-associated protein 1A/1B-light chain 3 (LC3), B cell lymphoma 2 (Bcl-2), caspase-3, bone morphogenetic protein 2 (BMP2), Beclin-1, autophagy-related 5 (ATG-5), Runt-related transcription factor 2 (RUNX-2), and receptor activator of nuclear factor kappa-b ligand (RANKL) protein in the vertebrae tissue were assessed by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot assay. RESULTS There was a significant (p<0.01) decrease in the BMD and microarchitectural parameters in the vertebrae tissue of the fangchinoline-treated group compared to the prednisolone group. We also found that treatment with fangchinoline attenuated the altered expressions of LC3, Bcl-2, caspase-3, BMP2, Beclin-1, ATG-5, RUNX-2, and RANKL protein in the prednisolone-induced osteoporosis rats. Moreover, levels of biochemical parameters were attenuated in the serum of fangchinoline-treated and prednisolone-induced osteoporosis rat. Histopathology revealed that the apoptosis of osteoblasts was decreased in the fangchinoline-treated group compared to the prednisolone group of rats. CONCLUSIONS Fangchinoline inhibits apoptosis of osteoblasts and protects against bone loss in prednisolone-induced osteoporosis rats by inducing autophagy.


Hepatitis E virus and related viruses in wild, domestic and zoo animals: A review.
Hepatitis E is a human disease mainly characterized by acute liver illness, which is caused by infection with the hepatitis E virus (HEV). Large hepatitis E outbreaks have been described in developing countries; however, the disease is also increasingly recognized in industrialized countries. Mortality rates up to 25% have been described for pregnant women during outbreaks in developing countries. In addition, chronic disease courses could be observed in immunocompromised transplant patients. Whereas the HEV genotypes 1 and 2 are mainly confined to humans, genotypes 3 and 4 are also found in animals and can be zoonotically transmitted to humans. Domestic pig and wild boar represent the most important reservoirs for these genotypes. A distinct subtype of genotype 3 has been repeatedly detected in rabbits and a few human patients. Recently, HEV genotype 7 has been identified in dromedary camels and in an immunocompromised transplant patient. The reservoir animals get infected with HEV without showing any clinical symptoms. Besides these well-known animal reservoirs, HEV-specific antibodies and/or the genome of HEV or HEV-related viruses have also been detected in many other animal species, including primates, other mammals and birds. In particular, genotypes 3 and 4 infections are documented in many domestic, wildlife and zoo animal species. In most cases, the presence of HEV in these animals can be explained by spillover infections, but a risk of virus transmission through contact with humans cannot be excluded. This review gives a general overview on the transmission pathways of HEV to humans. It particularly focuses on reported serological and molecular evidence of infections in wild, domestic and zoo animals with HEV or HEV-related viruses. The role of these animals for transmission of HEV to humans and other animals is discussed.


[Clinical predictors of hemorrhagic transformation in non lacunar ischemic stroke].
Hemorrhagic transformation is a complex phenomenon where brain tissue bleeds, which could be associated or not to an increase in the neurological deficit after the acute ischemic stroke. The aim of our study was to evaluate clinical predictors of hemorrhagic transformation in patients with non-lacunar ischemic stroke. We performed a prospective analysis of the clinical records and images of patients with non-lacunar ischemic stroke. Demographics, vascular risk factors, previous medications and the information of the event in patients with and without hemorrhagic transformation were here compared. We included in this study 747 patients with non-lacunar stroke, the mean age was 77 ± 11 years and 61% were females. In the univariate analysis, the age, a history of hypertension, atrial fibrillation, chronic kidney disease and the previous use of oral anticoagulation resulted statistically significant. In the multivariate analysis of logistic regression adjusted by age and vascular risk factors: the age > 80 years (OR 3.6, CI 95% 1.8-7.6), the pulse pressure > 60 mmHg at admission (OR 5.3, CI 95% 3.2-9.1), the chronic kidney disease (OR 3, CI 95% 2.5-3.8) and the presence of previous atrial fibrillation (OR 3.5, CI 95% 2.1-6.1) were associated with and increased risk of hemorrhagic transformation. The predictors of hemorrhagic transformation in our cohort showed a relationship with severe vascular illness. The identification of these patients could influence therapeutic decisions that could increase the risk of hemorrhagic transformation.


Interpreting Incidentally Identified Variants in Genes Associated With Catecholaminergic Polymorphic Ventricular Tachycardia in a Large Cohort of Clinical Whole-Exome Genetic Test Referrals.
The rapid expansion of genetic testing has led to increased utilization of clinical whole-exome sequencing (WES). Clinicians and genetic researchers are being faced with assessing risk of disease vulnerability from incidentally identified genetic variants which is typified by variants found in genes associated with sudden death-predisposing catecholaminergic polymorphic ventricular tachycardia (CPVT). We sought to determine whether incidentally identified variants in genes associated with CPVT from WES clinical testing represent disease-associated biomarkers. CPVT-associated genes RYR2 and CASQ2 variants were identified in one of the world's largest collections of clinical WES referral tests (N=6517, Baylor Miraca Genetics Laboratories) and compared with a control cohort of ostensibly healthy individuals (N=60 706) and a case cohort of CPVT cases (N=155). Within the WES cohort, the rate of rare variants in CPVT-associated genes was 8.8% compared with 6.0% among controls and 60.0% among cases. There was a predominance of variants of undetermined significance (97.7%). After protein topology mapping, WES variants colocalized more frequently to residues with variants found in controls compared with cases. Retrospective clinical evaluation of individuals referred to our institution with WES-positive variants demonstrated no evidence of clinical CPVT in individuals with a low pretest clinical suspicion for CPVT. The prevalence of incidentally identified CPVT-associated variants is ≈9% among WES tests. Variants of undetermined significances in CPVT-associated genes in WES genetic testing, in the absence of clinical suspicion for CPVT, are unlikely to represent markers of CPVT pathogenicity.


Diagnostic and therapeutic approach to persistent or recurrent fevers of unknown origin in adult stem cell transplantation and haematological malignancy.
Persistent or recurrent fevers of unknown origin (PFUO) in neutropenic patients on broad-spectrum antibiotics have traditionally been treated with empirical antifungal therapy (EAFT). The lack of survival benefit seen with the use of amphotericin B deoxycholate (AmB-D) as EAFT has been attributed to its toxicities. More recently, newer, less toxic and more expensive antifungal agents such as the lipid formulations of AmB, the newer azoles (fluconazole, itraconazole and voriconazole) and caspofungin have been analysed in a number of EAFT trials. Compared with AmB-D the newer agents have superior safety but are of equivalent efficacy. This lack of survival advantage is related to the fact that the trigger for commencement of EAFT is late and non-specific. Thus, alternative approaches are required. New sensitive serological and molecular tests for the detection of Aspergillus antigens and genomic DNA have been developed and evaluated in accuracy studies. These tests have been incorporated into management strategies (i.e. pre-emptive strategies) to direct antifungal therapy. The pre-emptive approach has been shown to be safe and feasible but its impact on clinically important patient outcomes such as survival is less clear. Other advances include the introduction of effective, non-toxic mould-active antifungal prophylaxis and patient risk-group stratification. In this paper we provide new evidence-based algorithms for the diagnosis and treatment of PFUO in adult patients undergoing stem cell transplantation and chemotherapy for haematological malignancy which incorporate these newer diagnostic tests and are directed by the risk category of the patient and type of antifungal prophylaxis the patient is receiving.


Angiotensin-induced desensitization of the phosphoinositide pathway in cardiac cells occurs at the level of the receptor.
Previous studies show that angiotensin II (Ang II) increases phosphoinositide turnover in cultured neonatal heart cells. Ang II has also been shown to transiently increase spontaneous beating behavior in these cells. In this study we seek to identify the molecular mechanism underlying this rapid (3-5-minute) desensitization. Time-course studies on the accumulation of [3H]inositol phosphates indicate that the loss in functional responsiveness correlates with reduced efficacy of Ang II to activate the phosphoinositide path. Binding studies with 125I-Ang II revealed that there was no change in surface receptor binding capacity during the time in which desensitization developed. Normal phosphoinositide and functional responses are observed when desensitized cells are treated with probes that activate the cardiac phosphoinositide pathway at discrete steps. These studies reveal that the functional status of the major components of the phosphoinositide signaling pathway, including G proteins, phospholipase C, and protein kinase C (PKC), are normal during maintained Ang II desensitization. To study the potential role of PKC in Ang II desensitization, the cells are treated with TPA for 24 hours, which downregulates PKC activity. PKC-depleted cells rapidly desensitize after Ang II application. We conclude that the selective Ang II-evoked biochemical/functional desensitization involves inhibition at the level of the receptor, rather than at a component downstream in the path, and that this process is independent of PKC and loss of surface binding capacity.


Effects of ultraviolet radiation on predatory mites and the role of refuges in plant structures.
Most studies on ecological impact of solar ultraviolet (UV) radiation generally focus on plants. However, UV radiation can also affect organisms at other trophic levels. Protection against mortality induced by solar UV has, therefore, been hypothesized as one of the reasons why Typhlodromalus aripo hides in the apex of cassava plants during the day and comes out at night to prey on spider mites on leaves. In laboratory experiments using UV lamps, we determined the impact of UVA and UVB radiation on survival and oviposition of two leaf-inhabiting mites (Amblydromalus manihoti, Euseius fustis) and the apex-inhabiting mite (T. aripo), all three species being predators used for controlling the cassava green mite Mononychellus tanajoa in Africa. Whereas on leaf discs UVA has no negative impact on survival of the three predators, UVB is lethal to all of them. In contrast, nearly 85% of T. aripo survived after exposure to UVB inside apex of cassava plants. Exposure of A. manihoti and E. fustis to UVB radiation on the lower surface of a cassava leaf resulted in 36% survival. Oviposition and hatching of eggs laid after exposure to UVB were not affected, but eggs directly exposed to UVB did not hatch. Although caution should be exercised to extrapolate laboratory studies to the field, our results support the hypothesis that lower side of leaves, but especially plant apices, represent refuges that protect predatory mites from UVB. This might explain why T. aripo moves out of the apex to forage on leaves only during the night.


An adherent-invasive Escherichia coli-colonized mouse model to evaluate microbiota-targeting strategies in Crohn's disease.
Adherent-invasive Escherichia coli (AIEC) were investigated for their involvement in the induction/chronicity of intestinal inflammation in Crohn's disease (CD). AIEC gut establishment is favoured by overexpression of the glycoprotein CEACAM6 in the ileal epithelium. We generated a transgenic mouse model, named 'Vill-hCC6', in which the human CEACAM6 gene was under the control of the villin promoter, conditioning expression in the small intestine. We demonstrated that CEACAM6 is strongly expressed in the small intestine mucosa and is correlated with numerous glycosylations displayed at the brush border of enterocytes. Ex vivo, the AIEC-enterocyte interaction was enhanced by CEACAM6 expression and necessitated the presence of the bacterial adhesive factor FimH. Finally, AIEC bacteria preferentially persisted in a FimH-dependent manner in the ileal mucosa of Vill-hCC6 mice compared to wild-type mice. This preclinical model opens new perspectives in the mechanistic study of the AIEC pathobiont and represents a valuable tool to evaluate the efficacy of new strategies to eliminate AIEC implanted in the ileal mucosa, such as phages, inhibitory and/or anti-virulence molecules, or CRISPR-based strategies targeting virulence or fitness factors of AIEC bacteria.


Genetic Analysis of African Swine Fever Virus From the 2018 Outbreak in South-Eastern Burundi.
African swine fever (ASF) is a contagious viral disease that causes high mortality, approaching 100%, in domestic pigs and wild boars. The disease has neither a cure nor a vaccine, and it is caused by an ASF virus (ASFV), the only member of the family Asfarviridae, genus Asfivirus, and the only known DNA arbovirus. Twenty-four genotypes of ASFV have been described to date, and all of them have been described in Africa. ASF is endemic in Burundi, and several outbreaks have been reported in the country; the disease continues to economically impact on small-scale farmers. This study aimed at genetic characterization of ASFV that caused an ASF outbreak in the Rutana region, Burundi, in the year 2018. Tissue samples from domestic pigs that died as a result of a severe hemorrhagic disease were collected in order to confirm the disease using polymerase chain reaction (PCR) and to conduct partial genome sequencing. Nucleotide sequences were obtained for the B646L (p72) gene, the intergenic fragment between the I73R and I329L genes, and the central variable region (CVR) of the B602L gene. Phylogenetic analysis of the Burundian 2018 ASFV grouped the virus within B646L (p72) genotype X and clustered together with those reported during the 1984 and 1990 outbreaks in Burundi with high nucleotide identity to some ASFV strains previously reported in neighboring East African countries, indicating a regional distribution of this ASFV genotype. Analysis of the intergenic fragment between I73R and I329L genes showed that the Burundian 2018 ASFV described in this study lacked a 32-base pair (bp) fragment present in the reference genotype X strain, Kenya 1950. In addition, the strain described in this study had the signature AAABNAABA at the CVR (B602L) gene and showed 100% amino acid sequence identity to viruses responsible for recent ASF outbreaks in the region. The virus described in this study showed high genetic similarities with ASFV strains previously described in domestic pigs, wild suids, and soft ticks in East African countries, indicating a possible common wild source and continuous circulation in domestic pigs in the region.


Thirty-year history of Irish (Rossmore) Ostrea edulis selectively bred for disease resistance to Bonamia ostreae.
The protistan pathogen Bonamia ostreae was first detected in Ostrea edulis at Rossmore, Cork Harbour, on the south coast of Ireland in 1987. A selective breeding programme commenced in 1988 by Atlantic Shellfish Ltd. to produce B. ostreae-resistant oysters using 3 to 4 yr old survivors as broodstock for controlled spawning in land-based spatting ponds. On-growing of oyster spat settled on mussel cultch was carried out on designated beds within Cork Harbour. Oyster production subsequently increased successfully, resulting in 3 yr old Rossmore O. edulis being marketed from 1993 onwards and a record tonnage of 4 yr old oysters being produced in 1995 and 1996. O. edulis production, B. ostreae prevalence and oyster mortalities have been monitored and recorded at Rossmore for over 30 yr. The collation and analysis of this data from 52 samples and 3190 oysters demonstrate the introduction and progression of bonamiosis and subsequent interventions to ameliorate disease effects during this period at Rossmore. Results suggest that O. edulis mortalities are now negligible during the first 4 yr of growth, prevalence of B. ostreae infection is low, and no correlation exists between prevalence of infection and oyster mortalities. This study, when compared to other studies of bonamiosis-infected oyster populations, suggests that an intervention in the form of a selective breeding programme is required to reduce the impact of the disease.


Secondary structure and molecular analysis of interstrain variability in the P5 outer-membrane protein of non-typable Haemophilus influenzae isolated from diverse anatomical sites.
The sequence of the non-typable Haemophilus influenzae (NTHi) P5 outer-membrane protein from a range of clinical isolates is presented and represents the first analysis of the heterogeneity in P5 from NTHi isolates from diverse anatomical sites. The basis of the previously observed inter-strain variation in the electrophoretic mobility is attributed to heterogeneity in three hypervariable regions. Alignment of the P5 sequences identified regions which are highly conserved and align with the transmembrane region predicted for the homologous Escherichia coli protein, OmpA. Variable regions correspond to surface-exposed loops, of which the first loop falls into subclasses. However, these subclasses fail to correlate with anatomical predisposition. Although P5 has been proposed as a fimbrial protein composed of coiled coils, both structural analysis by circular dichroism of purified P5 and computer analysis of the multiply aligned sequences predict a high proportion of beta strand with no evidence of coiled coil structure. A detailed model of P5 is presented.


Personalized pharmacotherapy in diabetes care using clinical pharmacology data of basal insulin analogues.
Advancement in technology led to the development of many insulin analogues in the last three decades. These analogues are characterized by various clinical pharmacology properties that can be utilized in clinical practice to tailor insulin therapy for each patient with diabetes, individually. This paper explores the different aspects of clinical pharmacology data on basal insulin analogues that can influence the choice of basal insulin for a personalized pharmacotherapy.


[Primary bilateral adrenal lymphoma].
When abdominal imaging reveals the existence of unsuspected adrenal masses, a diagnostic strategy is necessary. We report the case of a woman presenting with pulmonary embolism, in whom abdominal ultrasound revealed voluminous masses in both adrenals without clinical or biological signs of hormone hypersecretion, but with mild primary adrenal failure. From a CT scan-directed needle biopsy of the right adrenal mass and subsequent staging we were able to diagnose a primary bilateral adrenal lymphoma, diffuse large B-cell type (REAL/WHO). On CHOP chemotherapy both adrenal masses decreased dramatically and the patient is in remission 18 months later. Primary adrenal lymphoma is a rare condition, since 65 cases have been reported to date. Histological diagnosis is nevertheless important, in view of the excellent response to specific therapy observed in some cases.


Lifestyles and routine activities of South African teenagers at risk of being trafficked for involuntary prostitution.
The United Nations estimates that 79% of teenage girls trafficked globally every year are forced into involuntary prostitution. About 247 000 South African children work in exploitative conditions; about 40 000 South African female teenagers work as prostitutes. This paper investigates lifestyles and routine activities of teenagers at risk of being trafficked for involuntary prostitution. The key concepts involuntary prostitution, intergenerational sex and exploitative conditions are defined in relation to the lifestyles and routine activities of South African female teenagers. Human trafficking for involuntary prostitution is described, based on a literature review. Lifestyle exposure and routine activities theories help to explain the potential victimisation of these teenagers in human trafficking for involuntary prostitution. Actual lifestyle and routine activities of South African teenagers and risky behaviours (substance abuse, intergenerational sex and child prostitution) are discussed as factors that make teens vulnerable to such trafficking. This paper recommends that human trafficking prevention efforts (awareness programmes and information campaigns) be directed at places frequented by human traffickers and teenagers in the absence of a capable guardian to reduce victimisation, as traffickers analyse the lifestyles and routine activities of their targets. South Africa should also interrogate entrenched practices such as intergenerational sex.


[Development of a prototype of space vegetable-cultivating facility for ground-based experiments].
To develop a ground-based experimental prototype of space vegetable-cultivating facility (GEPSVF), so as to solve the main key techniques related to higher plant cultivation in space environmental conditions, and to further lay a foundation for future development and application of the prototype of space vegetable-growing facility. Based on detailed demonstration and design of technique plan, the blueprint design and machining of components, whole facility installment, debugging, trial operations and verification experiments were done. The parameters in the growing chamber such as temperature, relative humidity, wind velocity, total pressure, O2 partial pressure, CO2 partial pressure and water content of the growing media were totally and effectively controlled; the light source was electronic fluorescent lamp; the average vegetable-producing output reached 60 g (fresh weight) d-1. The prototype could operate stably; its actual performance indexes achieved the expected ones basically; some of its operating principles can adapt to space microgravity condition. Therefore, the prototype is a good beginning for future development of space vegetable-producing facilities.