The prevalence and economic importance of bovine fasciolosis in Kenya--an analysis of abattoir data.
A retrospective study covering a period of 10 years (1990-1999) was carried out using post mortem meat inspection records at the Veterinary Department Headquarters at Kabete to determine the prevalence and economic importance of bovine fasciolosis in Kenya. Meat inspection records from abattoirs in 38 districts distributed over seven out of the eight provinces of Kenya were examined. Prevalence of fasciolosis was calculated as the number of cattle found to be infected with Fasciola, expressed as a percentage of the total number of cattle slaughtered. Using the average weight and market price of a bovine liver, the monetary loss occasioned by condemnation of Fasciola infected livers was calculated. A survey was also carried out at Dagoretti slaughterhouse complex in Nairobi to determine the relative occurrence of F. gigantica and F. hepatica in slaughtered cattle. Cattle slaughtered at Dagoretti slaughterhouse originate from all parts of the country. A total of 5,421,188 cattle were slaughtered in the seven provinces of Kenya during the 10-year period and 427,931 (8%) of these cattle were infected with Fasciola. The region with the highest prevalence of fasciolosis was Western Province (16%) followed, in descending order, by Eastem Province (11%), Nyanza Province (9%), Rift Valley Province (8%), Central Province (6%), Nairobi Province (4%) and Coast Province (3.5%). The total economic loss incurred by the country during the 10-year period as a result of condemnation of the infected livers was approximately US$2.6 million. The total annual economic losses during this period ranged from approximately US$0.2-0.3 million. The highest total economic losses for the 10-year period were recorded in Western Province (US$0.8 million) and Central Province (US$0.7 million). A total of 1584 cattle originating from five provinces of Kenya were slaughtered at Dagoretti slaughterhouse over a period of two months of which 147 (9.3%) were infected with liver flukes. All the liver flukes obtained from the infected livers were identified as F. gigantica. It is concluded that fasciolosis is prevalent in cattle in all provinces of Kenya, that it causes great economic losses as a result of condemnation of infected livers, and that F. gigantica is the main species of liver flukes affecting cattle in Kenya. Local climatic factors, cattle trade, rustling and population numbers, and the presence of the snail intermediate hosts are probably the main factors influencing the incidence of the disease in the various regions of the country.


Photothermally-induced disordered patterns of corneal collagen revealed by SHG imaging.
The loss of organization of the corneal collagen lattice induced by photothermal effects was analyzed by using second-harmonic generation (SHG) imaging. Porcine cornea samples were treated with low-power laser irradiation in order to get localized areas of tissue disorganization. The disorder induced within the irradiated area of corneal stroma was quantified by means of Discrete Fourier Transform, auto-correlation and entropy analyses of the SHG images. Polarization modulated SHG measurements allowed to probe the changes in the structural anisotropy of sub-micron hierarchical levels of the stromal collagen. Our results emphasize the great potential of the SHG imaging to detect subtle modifications in the collagen assembly. The proposed analytical methods may be used to track several genetic, pathologic, accidental or surgical-induced disorder states of biological tissues.


Interference by venlafaxine ingestion in the detection of tramadol by liquid chromatography linked to tandem mass spectrometry for the screening of illicit drugs in human urine.
Confirmation of the presence of illicit drugs in human fluids by liquid chromatography linked to atmospheric pressure ionisation tandem mass spectrometry (LC/MS/MS) is becoming increasingly popular. A rapid LC/MS/MS method is described using reversed phase gradient elution chromatography on a 50 x 3 mm base deactivated C8 column with identification of drugs based on their Multiple Reaction monitoring (MRM) transitions, retention time, and co-elution of stable isotopic analogues where available. The method is used for drug confirmation following initial screening by immunoassay, and identification of drugs such as tramadol, for which no immunoassay is available. False positive results for tramadol were observed in cases where subjects were being treated with the commonly prescribed antidepressant drug venlafaxine. This was a result of the presence of the metabolite O-desmethylvenlafaxine, which has a similar transition to tramadol. This study highlights the need to consider drug metabolites, as well as parent drugs in interferences in LC/MS/MS methods.


Physiology and pathophysiology of incidental findings detected on FDG-PET scintigraphy.
A routine feature of positron emission tomography/computed tomography (PET/CT) imaging is whole-body acquisition that results in many unexpected findings identified outside of the primary region of abnormality. Furthermore, (18)F-fluorodeoxyglucose (FDG) is a marker of glycolysis and does not specifically accumulate in malignancy. Understanding the physiology and pathophysiology of normal FDG distribution and common incidental findings is therefore essential to the physician interpreting whole-body FDG-PET/CT studies. Whereas many incidental findings are benign and of limited clinical significance, others represent uncommon manifestations of the primary malignancy, second malignancies, or various clinically significant pathologic processes. Patients with a single malignancy are at greater risk of developing synchronous or metachronous second malignancies, possibly related to exposure to shared carcinogenic agents or presence of prooncogenic mutations. The decision of how to pursue an intervention on the basis of an incidental finding is generally left to clinical judgment.


Mercury-resistant bacteria and petroleum degradation.
The concentration of mercury in water and sediment and in the oil extracted from water and sediment was determined for samples collected in Colgate Creek, located in Baltimore Harbor of the Chesapeake Bay. The concentration of mercury in the oil was 4,000 times higher than in sediment and 300,000 times higher than in water samples. The mercury-resistant bacterial populations of the samples studied have been shown to degrade oil, suggesting these bacteria to be a significant factor in the degradation of oil in Colgate Creek.


[Vassili Dmitrievich Shervinsky, the leader of Russian therapists as a private person: the portrait in interieur].
Despite numerous publications devoted to role of Vasily Shervinsky as public figure, organizer and researcher, information about his private life is almost not described in historical literature. The article presents an attempt, based on archival sources and not numerous testimonies of contemporaries, to draw up portrait of V. D. Shervinsky against the background of his medical, social and universal historical milieu.


A variant at 9p21.3 functionally implicates CDKN2B in paediatric B-cell precursor acute lymphoblastic leukaemia aetiology.
Paediatric B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) is the most common cancer of childhood, yet little is known about BCP-ALL predisposition. In this study, in 2,187 cases of European ancestry and 5,543 controls, we discover and replicate a locus indexed by rs77728904 at 9p21.3 associated with BCP-ALL susceptibility (Pcombined=3.32 × 10(-15), OR=1.72) and independent from rs3731217, the previously reported ALL-associated variant in this region. Of correlated SNPs tagged by this locus, only rs662463 is significant in African Americans, suggesting it is a plausible causative variant. Functional analysis shows that rs662463 is a cis-eQTL for CDKN2B, with the risk allele associated with lower expression, and suggests that rs662463 influences BCP-ALL risk by regulating CDKN2B expression through CEBPB signalling. Functional analysis of rs3731217 suggests it is associated with BCP-ALL by acting within a splicing regulatory element determining CDKN2A exon 3 usage (P=0.01). These findings provide new insights into the critical role of the CDKN2 locus in BCP-ALL aetiology.


Rivaroxaban and apixaban in patients with atrial fibrillation; a real-world data.
This study aims to analyze the real-life data of patients who were prescribed rivaroxaban and apixaban and to emphasize the points that we think will make a difference compared to randomized controlled studies. The patients who accepted to participate in the study in whom rivaroxaban (15-20 mg) and apixaban (2.5-5 mg) were started with the diagnosis of atrial fibrillation between 01 January 2018 and 31 December 2019 and whose records were fully accessed through the hospital automation system were included in the study. One hundred and ninety-four (48.5%) of a total of 400 patients using rivaroxaban and apixaban were women. The mean age was 73.34 ± 10.45 years, and the age range was 41-98. There was no significant difference in terms of demographic characteristics, background information of the patients, and the medications. Drug-induced complications and mortality rates were also similar. The GFR change rates of the patients in both groups were similar even though the initial GFRs were significantly higher in rivaroxaban group. The mean age and ejection fractions of the patients using rivaroxaban 15 mg were found to be lower than those of patients using rivaroxaban 20 mg whereas the mean systolic blood pressure and HAS-BLED score were found to be higher. Ischemic stroke and mortality rates were higher in patients using 15 mg rivaroxaban than patients using 20 mg rivaroxaban. The rates of nonmajor bleeding in patients using rivaroxaban 15 mg were lower compared to those using 20 mg, and this difference was statistically significant. Stroke rates were found to be higher and to have similar bleeding rates compared to major clinical studies in our real-life analysis. However, high ischemic cerebrovascular event and low nonmajor bleeding rates are remarkable in low dose use of rivaroxaban. It is clear that there is a need to consider existing dose reduction criteria in terms of correct prescribing.


Changes in collagen stability and folding in lethal perinatal osteogenesis imperfecta. The effect of alpha 1 (I)-chain glycine-to-arginine substitutions.
The effect of glycine-to-arginine mutations in the alpha 1 (I)-chain on collagen triple-helix structure in lethal perinatal osteogenesis imperfecta was studied by determination of the helix denaturation temperature and by computerized molecular modelling. Arginine substitutions at glycine residues 391 and 667 resulted in similar small decreases in helix stability. Molecular modelling suggested that the glycine-to-arginine-391 mutant resulted in only a relatively small localized disruption to the helix structure. Thus the glycine-to-arginine substitutions may lead to only a small structural abnormality of the collagen helix, and it is most likely that the over-modification of lysine, poor secretion, increased degradation and other functional sequelae result from a kinetic defect in collagen helix formation resulting from the mutation.


Postinfarct Left Ventricular Remodelling: A Prevailing Cause of Heart Failure.
Heart failure is a chronic disease with high morbidity and mortality, which represents a growing challenge in medicine. A major risk factor for heart failure with reduced ejection fraction is a history of myocardial infarction. The expansion of a large infarct scar and subsequent regional ventricular dilatation can cause postinfarct remodelling, leading to significant enlargement of the left ventricular chamber. It has a negative prognostic value, because it precedes the clinical manifestations of heart failure. The characteristics of the infarcted myocardium predicting postinfarct remodelling can be studied with cardiac magnetic resonance and experimental imaging modalities such as diffusion tensor imaging can identify the changes in the architecture of myocardial fibers. This review discusses all the aspects related to postinfarct left ventricular remodelling: definition, pathogenesis, diagnosis, consequences, and available therapies, together with experimental interventions that show promising results against postinfarct remodelling and heart failure.


[A prototype double coil for MR breast measurement].
The first application of a double coil for routine MR mammography is described: by this method it is possible to examine both breasts simultaneously. This is important in order to halve the time of the examination and to allow comparison of the two breasts during dynamic contrast studies. The reduction in signal-to-noise ratio, compared with a single coil and flow artifacts of the heart do not interfere with diagnosis. The axillary region is better shown than with a single coil. Examination of 22 patients with subsequent histological control has shown that the information about signal increase after the injection of Gd-DTPA obtained from single coil can be applied equally to the double coil.


Quantitative electron-paramagnetic-resonance measurements of the electron-transfer components of the photosystem-I reaction centre.
E.p.r. spectrometry was used to investigate the quantitative relationships between the oxidized chlorophyll free-radical signal I and the reduced iron-sulphur centre-A signal generated on illuminating Photosystem-I particles at cryogenic temperatures. In Photosystem-I particles prepared by using the French press or Triton X-100, at pH8.0 in the presence and absence of ascorbate and at pH 10.0 in the presence of ascorbate, the size of the light-induced signal I and iron-sulphur centre-A signals, corresponded to equal numbers of unpaired electron spins in each component. At 77K the spin-lattice relaxation time, T1, of the free radical signal I in samples of Photosystem-I particles prepared with Triton X-100 in the absence of ascorbate was 0.68 times the T1 value in the presence of ascorbate. Such changes in relaxation time can account for the different quantitative conclusions incorrectly arrived at from measurements made at saturating microwave powers [Bearden & Malkin (1976) Biochem. Biophys. Acta 430, 538-547; Malkin & Bearden (1976) FEBS Lett. 69, 216-220]. In the presence of benzoquinone and ferricyanide the ratio of free radical to centre A was 2.96:1, and at 77K the T1 was 0.50 times the T1 for ascorbate-treated samples. Here free radicals from bulk chlorophyll are generated in addition to those from the reaction-centre chlorophyll.


Self-reported hearing difficulty versus audiometric screening in younger and older smokers and nonsmokers.
The high incidence of age-related hearing loss demands accessible, low cost hearing screenings for prevention and hearing health promotion. This study assessed performance of self report (SR) against audiometry, and prevalence of hearing difficulty when screening hearing in middle-aged and younger adults, including smokers and nonsmokers. Prospective participants (N = 219) completed a questionnaire providing biographical, health, and smoking information. Their Yes/No responses about hearing or communication difficulty provided data for self-reported hearing loss. Eligible (N = 170) participants received a hearing test including immittance, pure-tone, and speech audiometry. The binaural pure-tone average (PTA) hearing threshold was determined; PTA decibel (dB) level indicated degree (e.g., mild) of hearing loss. All hearing screening data were coded and initially analyzed in an Access database. Statistical analyses based on conditional probability included measures of prevalence, sensitivity, specificity, and predictive value of the SR versus audiometric measures. Participants provided a urine sample for biochemical analysis to confirm smoker/nonsmoker status. Among all participants (N = 170), overall prevalence of self-reported hearing difficulty (15.9%) was in excellent agreement with measured, mild hearing loss (16.5%). However, factoring in age and smoking revealed that SR was incongruent with audiometry because hearing loss was overestimated by smokers and younger participants and underestimated by middle-aged individuals. The SR question yielded high specificity (80-90%) overall. Specificity was highest in nonsmokers (89-94%) and younger (90-91%) individuals with lower performance in smokers and middle-aged participants. SR sensitivity was high (86-100%) only when the hearing impairment cutoff was > 40 dB (moderate loss) and > 60 dB (severe loss). Sensitivity was highest in smokers (100%), supporting SR for screenings. High negative and low positive predictive value (PPV) occurred in smokers, younger, and middle-aged persons. This study reports new sensitivity and specificity data on self-reported hearing difficulty in smokers (N = 98), younger (N = 80), and middle-aged (N = 90) adults, indicating efficacy of SR as an adult hearing screening measure. SR was effective as few normal-hearing persons were labeled hearing-impaired. However, audiometry should supplement SR to optimize detection of mild hearing loss for at-risk adults. Results may guide community health initiatives for hearing screenings, prevention, and health promotion. Aging; Smoking; Self Report; Health Promotion; Hearing Screening.


The emerging science of epigenomics.
One of the most exciting frontiers in both epigenetics and genome sciences is the new field of epigenomics. This new discipline promises novel insights into the genome because of its potential to detect quantitative alterations, multiplex modifications and regulatory sequences outside of genes. A number of new epigenomic strategies are emerging to exploit microarray formats with varying substrate choice, pre-processing and data analysis. These approaches are designed to detect large numbers of variations in DNA methylation and chromatin modification. Many groups are joining forces toward developing an organized Human Epigenome Project to exploit these new technologies to better understand the basis of normal development and human disease.


Biochemical and immunological studies of proteins from polydnavirus Chelonus sp. near curvimaculatus.
Polydnavirus from Chelonus sp. curvimaculatus (CcV) was purified and 18 structural polypeptides associated with CcV were identified by silver staining. Antibodies were raised against CcV protein and used in testing for ovary and in stung eggs. It was also established that the virus does not enter during the first 5 s of oviposition. Furthermore, no degradation of the virus proteins was Detected inside the egg within 2 h after oviposition. The glycoprotein nature of virus proteins was also determined by concanavalin A/horseradish peroxidase staining. The amino acid compositions of the most highly abundant peptides (41K, 33K, 21K, 17K and 13K) were determined, as was the N-terminal amino acid sequence of the 41K protein. The latter did not show similarity with any reported protein sequences.


Analysis of decisional conflict among parents who consent to hypospadias repair: single institution prospective study of 100 couples.
Although obtaining informed consent for distal hypospadias repair is common practice, little is known about the uncertainty or conflict between consenting parents faced with this decision. We systematically evaluated decisional conflict between parents who elected to have their child undergo hypospadias surgery. A total of 100 couples who were counseled about treatment options agreed to participate. Using a validated questionnaire, the Decisional Conflict Scale, we prospectively collected data on decisional conflict demographics, preference for circumcision, education level and prior knowledge about hypospadias. All parents elected surgical repair. Evidence of decisional conflict was encountered in 28% of participants (score less than 25 in 72%, 25 to 37.5 in 23.5%, greater than 37.5 in 4.5%). No statistically significant differences among parents were noted for total score (mean ± SD 16.1 ± 12 in mothers and 18.3 ± 12.6 in fathers) or subscales, except the informed subscale (mean ± SD 16.7 ± 14.3 in mothers and 21.1 ± 16.6 in fathers). Parental self-report of prior knowledge about hypospadias and preference for neonatal circumcision correlated with lower Decisional Conflict Scale scores (p = 0.02 and p <0.01, respectively). No statistical association was found between score and parental education level (p = 0.7) or expertise of the counselor (staff vs pediatric urology fellow, p = 0.4). These data describe the level of decisional conflict in couples agreeing to proceed with hypospadias repair, with no evidence of significant discrepancy between them. The novel description of factors related to decreased decisional conflict might help focus efforts aimed at minimizing difficulties encountered during the decision making process.


Stream hydrology limits recovery of riparian ecosystems after wolf reintroduction.
Efforts to restore ecosystems often focus on reintroducing apex predators to re-establish coevolved relationships among predators, herbivores and plants. The preponderance of evidence for indirect effects of predators on terrestrial plant communities comes from ecosystems where predators have been removed. Far less is known about the consequences of their restoration. The effects of removal and restoration are unlikely to be symmetrical because removing predators can create feedbacks that reinforce the effects of predator loss. Observational studies have suggested that the reintroduction of wolves to Yellowstone National Park initiated dramatic restoration of riparian ecosystems by releasing willows from excessive browsing by elk. Here, we present results from a decade-long experiment in Yellowstone showing that moderating browsing alone was not sufficient to restore riparian zones along small streams. Instead, restoration of willow communities depended on removing browsing and restoring hydrological conditions that prevailed before the removal of wolves. The 70-year absence of predators from the ecosystem changed the disturbance regime in a way that was not reversed by predator reintroduction. We conclude that predator restoration may not quickly repair effects of predator removal in ecosystems.


Ictal dysprosody and the role of the non-dominant frontal operculum.
Prosody is an important feature of language and refers to variations in the acoustic properties of timing, intensity and fundamental frequency that are used to convey affective or linguistic information. The prosodic component of ictal speech has not yet been specifically studied in epileptic patients. We report the case of a patient with right mesial temporal lobe epilepsy who developed ictal, recurrent speech utterances associated with an altered prosody during both spontaneous seizures and a very localized stimulation-induced discharge of the non-dominant precentral operculum, a finding consistent with results of functional magnetic resonance imaging studies in healthy subjects. This should prompt future studies, with the aim of better evaluating the localizing value of ictal dysprosody in patients with drug resistant, partial epilepsy.


Snakes partition their body to traverse large steps stably.
Many snakes live in deserts, forests and river valleys and traverse challenging 3-D terrain such as rocks, felled trees and rubble, with obstacles as large as themselves and variable surface properties. By contrast, apart from branch cantilevering, burrowing, swimming and gliding, laboratory studies of snake locomotion have focused on locomotion on simple flat surfaces. Here, to begin to understand snake locomotion in complex 3-D terrain, we studied how the variable kingsnake, a terrestrial generalist, traversed a large step of variable surface friction and step height (up to 30% snout-vent length). The snake traversed by partitioning its body into three sections with distinct functions. Body sections below and above the step oscillated laterally on horizontal surfaces for propulsion, whereas the body section in between cantilevered in a vertical plane to bridge the large height increase. As the animal progressed, these three sections traveled down its body, conforming overall body shape to the step. In addition, the snake adjusted the partitioned gait in response to increase in step height and decrease in surface friction, at the cost of reduced speed. As surface friction decreased, body movement below and above the step changed from a continuous lateral undulation with little slip to an intermittent oscillatory movement with much slip, and initial head lift-off became closer to the step. Given these adjustments, body partitioning allowed the snake to be always stable, even when initially cantilevering but before reaching the surface above. Such a partitioned gait may be generally useful for diverse, complex 3-D terrain.


Mitochondrial neurogastrointestinal encephalomyopathy.
Mitochondrial neurogastrointestinal encephalomyopathy is an autosomal recessive disorder in which a nuclear mutation of the thymidine phosphorylase gene leads to mitochondrial genomic dysfunction. Herein, we report a 29-year-old Iranian man with abdominal pain, diarrhea, hearing loss, ophthalmoplegia, sensorimotor axonal neuropathy, and elevated muscle enzymes. Magnetic resonance imaging showed leukoencephalopathic changes. Metabolite analysis revealed a very high thymidine concentration in the patient's urine consistent with the diagnosis of mitochondrial neurogastrointestinal encephalomyopathy.


Cognate DNA Recognition by Engrailed Homeodomain Involves a Conformational Change Controlled via an Electrostatic-Spring-Loaded Latch.
Transcription factors must scan genomic DNA, recognize the cognate sequence of their control element(s), and bind tightly to them. The DNA recognition process is primarily carried out by their DNA binding domains (DBD), which interact with the cognate site with high affinity and more weakly with any other DNA sequence. DBDs are generally thought to bind to their cognate DNA without changing conformation (lock-and-key). Here, we used nuclear magnetic resonance and circular dichroism to investigate the interplay between DNA recognition and DBD conformation in the engrailed homeodomain (enHD), as a model case for the homeodomain family of eukaryotic DBDs. We found that the conformational ensemble of enHD is rather flexible and becomes gradually more disordered as ionic strength decreases following a Debye-Hückel's dependence. Our analysis indicates that enHD's response to ionic strength is mediated by a built-in electrostatic spring-loaded latch that operates as a conformational transducer. We also found that, at moderate ionic strengths, enHD changes conformation upon binding to cognate DNA. This change is of larger amplitude and somewhat orthogonal to the response to ionic strength. As a consequence, very high ionic strengths (e.g., 700 mM) block the electrostatic-spring-loaded latch and binding to cognate DNA becomes lock-and-key. However, the interplay between enHD conformation and cognate DNA binding is robust across a range of ionic strengths (i.e., 45 to 300 mM) that covers the physiologically-relevant conditions. Therefore, our results demonstrate the presence of a mechanism for the conformational control of cognate DNA recognition on a eukaryotic DBD. This mechanism can function as a signal transducer that locks the DBD in place upon encountering the cognate site during active DNA scanning. The electrostatic-spring-loaded latch of enHD can also enable the fine control of DNA recognition in response to transient changes in local ionic strength induced by variate physiological processes.


Adult generation of glutamatergic olfactory bulb interneurons.
The adult mouse subependymal zone (SEZ) harbors neural stem cells that are thought to exclusively generate GABAergic interneurons of the olfactory bulb. We examined the adult generation of glutamatergic juxtaglomerular neurons, which had dendritic arborizations that projected into adjacent glomeruli, identifying them as short-axon cells. Fate mapping revealed that these originate from Neurog2- and Tbr2-expressing progenitors located in the dorsal region of the SEZ. Examination of the progenitors of these glutamatergic interneurons allowed us to determine the sequential expression of transcription factors in these cells that are thought to be hallmarks of glutamatergic neurogenesis in the developing cerebral cortex and adult hippocampus. Indeed, the molecular specification of these SEZ progenitors allowed for their recruitment into the cerebral cortex after a lesion was induced. Taken together, our data indicate that SEZ progenitors not only produce a population of adult-born glutamatergic juxtaglomerular neurons, but may also provide a previously unknown source of progenitors for endogenous repair.


A Novel Use of Methylene Blue in the Pediatric ICU.
Methylene blue (MB) is a medication commonly used to treat methemoglobinemia, reducing methemoglobin to hemoglobin. A novel use of MB, as detailed here, is in the treatment of refractory hypotension. A number of reports have detailed use of MB for this purpose in adults, but few data in pediatrics. A 22-month-old girl with Noonan syndrome, biventricular hypertrophic cardiomyopathy, and chronic positive pressure ventilation developed shock with tachycardia, hypotension, and fever after 3 days of diarrhea. She was critically ill, with warm extremities, bounding pulses, and brisk capillary refill. Laboratory tests revealed metabolic acidosis, low mixed venous oxygen saturation, and leukocytosis with bandemia. Treatment of severe septic shock was initiated with fluid resuscitation, inotropic support, sedation, and paralysis. She remained hypotensive despite norepinephrine at 0.7 μg/kg per minute, dopamine at 20 μg/kg per minute, and vasopressin at 0.04 U/kg per hour. Her vasoplegic shock worsened, despite aggressive conventional therapy. Intravenous MB was initiated, with a loading dose of 1 mg/kg followed by a continuous infusion at 0.25 mg/kg per hour. Upon initiation of MB, her systolic blood pressure increased by 33 points (40% increase), and diastolic blood pressure increased by 20 points (46% increase). She was able to wean off all inotropes quickly after initiation of MB. MB should be considered in the setting of refractory vasoplegic shock in the PICU.


The complement-mediated prozone effect in the Luminex single-antigen bead assay and its impact on HLA antibody determination in patient sera.
The Luminex xMAP system has become an important tool for HLA antibody screening and identification in sera of transplant patients. Recently, the Luminex single antigen bead assay was shown to be prone to an artefact, the so called prozone phenomenon: Sera with high titer HLA antibodies gave negative results when tested neat, but reacted strongly positive after 1:10 dilution. We also observed such a phenomenon and found that it was most likely caused by the complement component 1 (C1) by competitively displacing the detection antibodies. In this article we review the complement-mediated prozone effect and other mechanisms of interference with solid phase assays, and we discuss possible consequences for HLA antibody testing with the Luminex SAB assay.


Relationship between uric acid levels and cardiometabolic findings in a large cohort of β-thalassemia major patients.
to evaluate the relationship between uric acid (UA), hepatic and cardiac iron overload (T2*-MRI), ferritin, endocrinological diseases and cardiac complications in a large thalassemia major (TM) cohort. A total of 369 TM patients (187 men; 33 ± 6 years) were retrospectively studied, from the myocardial iron overload in thalassemia (MIOT) electronic databank. Multiple regression model identified male sex (p < 0.001), BMI (p < 0.001) and T2* (p ≤ 0.001) as UA independent correlates. Moreover, UA and derivatives of reactive oxygen species (an oxidative index; r = -0.3; p ≤ 0.05) are inversely correlated. Conversely, the multivariate logistic analysis identified low UA (NANHES-III criteria) as one independent predictor for low global heart T2* (p < 0.5) together with liver iron concentrations (>3 mg/g/dw), heart failure, endocrinopathies, ferritin (>2000 ng/l), alanine transaminase (>40 UI/l) and/or aspartate transaminase (>35 UI/l) and/or glutamyl transferase (>64 UI/l). UA appears directly associated to T2* and inversely with derivatives of reactive oxygen species, and as such reduced according to increased oxidative stress and cardiac iron overload in TM patients.


Assessing the global reach and value of a provider-facing healthcare app using large-scale analytics.
The rapid global adoption of mobile health (mHealth) smartphone apps by healthcare providers presents challenges and opportunities in medicine. Challenges include ensuring the delivery of high-quality, up-to-date and optimised information. Opportunities include the ability to study global practice patterns, access to medical and surgical care and continuing medical education needs. We studied users of a free anaesthesia calculator app used worldwide. We combined traditional app analytics with in-app surveys to collect user demographics and feedback. 31 173 subjects participated. Users were from 206 countries and represented a spectrum of healthcare provider roles. Low-income country users had greater rates of app use (p<0.001) and ascribed greater importance of the app to their practice (p<0.001). Physicians from low-income countries were more likely to adopt the app (p<0.001). The app was used primarily for paediatric patients. The app was used around the clock, peaking during times typical for first start cases. This mHealth app is a valuable decision support tool for global healthcare providers, particularly those in more resource-limited settings and with less training. App adoption and use may provide a mechanism for measuring longitudinal changes in access to surgical care and engaging providers in resource-limited settings. In-app surveys and app analytics provide a window into healthcare provider behaviour at a breadth and level of detail previously impossible to achieve. Given the potentially immense value of crowdsourced information, healthcare providers should be encouraged to participate in these types of studies.


Rapid detection of cellulose and hemicellulose contents of corn stover based on near-infrared spectroscopy combined with chemometrics.
The feasibility of near-infrared spectroscopy (NIRS) combined with chemometrics for the rapid detection of the cellulose and hemicellulose contents in corn stover is discussed. Competitive adaptive reweighted sampling (CARS) and genetic simulated annealing algorithm (GSA) were combined (CARS-GSA) to select the characteristic wavelengths of cellulose and hemicellulose and to reduce the dimensionality and multicollinearity of the NIRS data. The whole spectra contained 1845 wavelength variables. After CARS-GSA optimization, the number of characteristic wavelengths of cellulose (hemicellulose) was reduced to 152 (260), accounting for 8.24% (14.09%) of all wavelengths. The coefficients of determination of the regression models for predicting the cellulose and hemicellulose contents were 0.968 and 0.996, the root mean square errors of prediction (RMSEPs) were 0.683 and 0.648, and the residual predictive deviations (RPDs) were 5.213 and 16.499, respectively. The RMSEP of the cellulose and hemicellulose regression models was 0.152 and 0.190 lower for CARS-GSA than for the full-spectrum, and the RPD was increased by 0.949 and 3.47, respectively. The results showed that the CARS-GSA model substantially reduced the number of characteristic wavelengths and significantly improved the predictive ability of the regression model.


Uptake and Biotransformation of Spirotetramat and Pymetrozine in Lettuce (Lactuca sativa L. var. ramosa Hort.).
Here, we investigated the uptake, transport, and subcellular distribution of the pesticides pymetrozine and spirotetramat, and spirotetramat metabolites B-enol, B-glu, B-mono, and B-keto, under hydroponic conditions. Spirotetramat and pymetrozine exhibited high bioconcentrations in lettuce roots, with both having root concentration factor (RCF) values >1 after exposure for 24 h. The translocation of pymetrozine from roots to shoots was higher than that of spirotetramat. Pymetrozine is absorbed in roots mainly via the symplastic pathway and is primarily stored in the soluble fraction of lettuce root and shoot cells. The cell wall and soluble fractions were the major enrichment sites of spirotetramat and its metabolites in root cells. Spirotetramat and B-enol were mainly enriched in the soluble fractions of lettuce shoot cells, whereas B-keto and B-glu accumulated in cell walls and organelles, respectively. Both symplastic and apoplastic pathways were involved in spirotetramat absorption. Pymetrozine and spirotetramat uptake by lettuce roots was passive, with no aquaporin-mediated dissimilation or diffusion. The findings of this study enhance our understanding of the transfer of pymetrozine, spirotetramat, and spirotetramat metabolites from the environment to lettuce, and their subsequent bioaccumulation. This study describes a novel approach for the efficient management of lettuce pest control using spirotetramat and pymetrozine. At the same time, it is of great significance to evaluate the food safety and environmental risks of spirotetramat and its metabolites.


The effects of patient handoff characteristics on subsequent care: a systematic review and areas for future research.
To summarize the available evidence about patient handoff characteristics and their impact on subsequent patient care in hospitals. In January and February 2011, the authors searched the Cochrane Central Register of Controlled Trials, PubMed, Embase, CINAHL, PsycINFO, ERIC, ISI Web of Science, and the reference lists of relevant articles to carry out their systematic review. They selected articles that (1) had patient handoffs in hospitals as their explicit research focus and (2) reported at least one statistical test of an association between a handoff characteristic and outcome. They assessed study quality using 11 quality indicators. The authors identified 18 articles reporting 37 statistical associations between a handoff characteristic and outcome. The only handoff characteristic investigated in more than one study was the use of a standardized handoff sheet. Seven of those 12 studies reported significant improvements after introduction of the sheet. Four of the 18 studies used a randomized controlled trial design. Published research is highly diverse and idiosyncratic regarding the handoff characteristics and outcomes assessed and the methodologies used, so comparing studies and drawing general conclusions about the field are difficult endeavors. The quality of research on the topic is rather preliminary, and there is not yet enough research to inform evidence-based handoff strategies. Future research, then, should focus on research methods, which outcomes should be assessed, handoff characteristics beyond information transfer, mechanisms that link handoff characteristics and outcomes, and the conditions that moderate the characteristics' effects.


Revealing the Introduction History and Phylogenetic Relationships of Passiflora foetida sensu lato in Australia.
Genomic analysis can be a valuable tool to assistmanagement of non-native invasive species, through determining source and number of introductions as well as clarifying phylogenetic relationships. Here, we used whole chloroplast sequencing to investigate the introduction history of Passiflora foetida sensu lato in Australia and clarify its relationship with other Passiflora species present. Phylogenetic analysis of chloroplast genome data identified three separate genetic lineages of P. foetida s. l. present in Australia, indicating multiple introductions. These lineages had affinities to samples from three separate areas within the native range in Central and South America that represented phylogenetically distinct lineages. These results provide a basis for a targeted search of the native range of P. foetida s. l. for candidate biological control agents that have co-evolved with this species and are thus better adapted to the lineages that are present in Australia. Results also indicated that the Passiflora species native to Australia are in a separate clade to that of P. foetida s. l. and other introduced Passiflora species cultivated in Australia. This knowledge is important to assess the likelihood of finding biological control agents for P. foetida s. l. that will be sufficiently host-specific for introduction in Australia. As P. foetida s. l. is a widespread non-native invasive species across many regions of the world, outcomes from this work highlight the importance of first evaluating the specific entities present in a country before the initiation of a biological control program.


Comb polymers prepared by ATRP from hydroxypropyl cellulose.
Hydroxypropyl cellulose (HPC) was used as a core molecule for controlled grafting of monomers by ATRP, the aim being to produce densely grafted comb polymers. HPC was either allowed to react with an ATRP initiator or the first generation initiator-functionalized 2,2-bis(methylol)propionic acid dendron to create macroinitiators having high degrees of functionality. The macroinitiators were then "grafted from" using ATRP of methyl methacrylate (MMA) or hexadecyl methacrylate. Block copolymers were obtained by chain extending PMMA-grafted HPCs via the ATRP of tert-butyl acrylate. Subsequent selective acidolysis of the tert-butyl ester moieties was performed to form a block of poly(acrylic acid) resulting in amphiphilic block copolymer grafts. The graft copolymers were characterized by 1H NMR and FT-IR spectroscopies, DSC, TGA, rheological measurements, DLS, and tapping mode AFM on samples spin coated upon mica. It was found that the comb (co)polymers were in the nanometer size range and that the dendronization had an interesting effect on the rheological properties.


Patient-Reported Outcome Measures With Secondary Lower Limb Lymphedemas: A Systematic Review.
Patient-reported outcome measures are measures of patients' health-related quality of life. They should be added to other lymphedema measurements. With an improved disease-free survival of secondary lower limb lymphedema, attention must focus on such assessments. The objectives of this study were to locate and critically appraise suitable patient-reported outcomes measures for lower limb lymphedemas and search for existing valid translations for native German speakers. A systematic literature research was conducted. 20 semantical categories for qualitative analysis were evolved. Six questionnaires available in English and some in validated translations remained for analysis. Lower limb lymphedema patients experience poor quality of life, and one of the most critical denominators is skin quality. To establish skin care and prevent cellulitis, patients must learn about skin problems. Only two tools asked for past infections. This is considered crucial because of knowledge building and prophylactic behavior. Questions on movement restrictions were available in one questionnaire. As these have a close connection to one's ability to perform activities of daily life, they can affect quality of life. Afflicted patients have problems with the choice and availability of clothing. Only three questionnaires asked questions about clothing or shoes. Lymphedema patients are exposed to more psychological stress than healthy subjects, but only three questionnaires covered questions about this burden. There was a lack of reporting on psychometric data (Cronbach's alpha, intraclass correlation), which hinders the external validity. Analyzed questionnaires were available in English but only one in German. The analyzed questionnaires were in English, and only one was adapted and tested for native German speakers. For clinical practice, Devoogdt's questionnaire is recommended despite some shortcomings. There is a need for validated lymphedema questionnaires in German.


Whole-Slide Imaging Allows Pathologists to Work Remotely in Regions with Severe Logistical Constraints Due to Covid-19 Pandemic.
In this study, we report on our experience using digital pathology to overcome the severe limitations imposed on health care by the Covid-19 outbreak in Northern Italy. Social distancing had a major impact on public transportation, causing it to run with reduced timetables. This resulted in a major challenge for hospital commuters. To limit the presence in our hospital of no more than two pathologists at a time out of four, a web-based digital pathology system (DPS) was employed to work remotely. We used a DPS in which a scanner, a laboratory information system, a storage device, and a web server were interfaced so that tissue slides could be viewed over the Internet by whole-slide imaging (WSI). After a brief internal verification test, the activity on the DPS was recorded, taking track of a set of performance and efficiency indicators. At the end of the study, 405 cases were signed out remotely. Of 693 cases, 58.4% were signed out remotely by WSI, while 8.4% needed to be kept on hold to return to the original microscope slide. In three cases, at least one slide had to be rescanned. In eight cases, one slide was recut. Panel discussion by WSI was necessary in 34 cases, a condition in which all pathologists were asked for their opinion. A consultation with a more experienced colleague was necessary in 17 cases. We show that WSI easily allows pathologists to overcome the problems caused by the severe social distancing measures imposed by the Covid-19 pandemic. Our experience shows that soon there will not be alternatives to digital pathology, given that there is no assurance that other similar outbreaks will not occur.


Adenylate cyclase, cyclic nucleotide phosphodiesterase, and phosphorylase activity of cardiomyopathic hamster hearts.
Activities of adenylate cyclase in homogenates were reduced, whereas those of phosphodiesterases were elevated in hearts of myopathic hamsters (BIO 82.62). Affinities for either Mg2+ or ATP of cyclase were unaffected in myopathy. Ca2+ stimulation particulate phosphodiesterases was not observed in myopathy. Although the cardiac phosphorylase content was reduced at the advanced stages of myopathy,-AMP/+AMP ratios remained similar to those found in normal hearts.


Characterization of katD, a kinesin-like protein gene specifically expressed in floral tissues of Arabidopsis thaliana.
Kinesin and kinesin-like proteins (KLPs) are microtubule-based motor proteins that play important roles in organelle transport. Based on the homology to these proteins, a katD cDNA has now been isolated from a library prepared from flowers of Arabidopsis thaliana ecotype Columbia. Sequence analysis of the katD cDNA revealed an open reading frame of 2691bp [corrected], encoding a protein of 987 amino acids. Comparison of the nucleotide sequences of katD genomic and cDNA clones revealed the presence of 18 introns, 17 of which conform to the GU-AG rule. The central region of the KatD polypeptide exhibits substantial amino acid sequence homology to the motor domain of kinesin heavy chains, although the motor domain of KatD appears to be phylogenetically distant from those of other KLPs in plants. The amino-terminal region of KatD shares marked sequence similarity with the calponin homology domain, whereas the approximately 240-residue carboxyl-terminal region shows no significant homology to other known proteins. The predicted secondary structure of KatD revealed the lack of an alpha-helical coiled coil structure typical of kinesin heavy chains, suggesting that KatD may function as a monomeric motor. A recombinant truncated KatD protein containing the putative motor domain was shown both to bind to mammalian microtubules in a manner dependent on a non-hydrolyzable ATP analog, and to possess microtubule-dependent ATPase activity. Immunoblot and Northern blot analyses showed that both KatD protein and mRNA are expressed specifically in floral tissues. These results suggest that the structurally distinct KatD protein functions as a floral tissue-specific motor protein.


Gallstone formation in hamsters: effect of varying animal and vegetable protein levels.
The lithogenic diet routinely used for production of gallstones in hamsters contains 20% casein. It has previously been shown that replacement of casein by soy protein significantly decreases gallstone formation. In this study hamsters were fed a lithogenic diet containing casein (C), soy isolate (S), C/S 3:1, C/S 1:1, and C/S 1:3. The percentages of hamsters with gallstones on these five diets were: 44, 12, 38, 23, and 15. Biliary cholesterol levels and lithogenic index both decreased significantly with increasing levels of soy protein. Dilution of casein with soy protein progressively decreases lithogenicity.


The growth of gerontology and geriatrics in Mexico: Past, present, and future.
Life expectancy is increasing in Mexico, creating new opportunities and challenges in different areas, including gerontology and geriatric education and research. Although in the European Union there are more than 3,000 institutions that focus on aging research, in Latin America there are only 250 programs where theoretical and practical knowledge is taught. In Mexico, the number of institutions that offer gerontology and geriatric education is relatively small. One of the major concerns is that Mexico is not adequately prepared to optimally deal with the aging of its population. Thus, the main challenge that Mexico faces is to train practitioners, researchers, and policy makers to be able to respond to the aging priorities of this country. The goal of this review is to investigate the literature regarding 60 years in the fields of gerontology and geriatrics in Mexico. Even when programs have evolved within the past decades, there are some challenges to gerontological and geriatric education and aging research in Mexico. The implications for Mexico are discussed, as well as opportunities for moving these fields forward.


Importance of Long-term Low-Dose CT Follow-up after Negative Findings at Previous Lung Cancer Screening.
Purpose To assess the incidence of lung cancer in a cohort of patients with negative findings at previous lung cancer screening. Materials and Methods In this prospective cohort study, the authors first identified 4782 individuals who had negative screening results as part of the International Early Lung Cancer Action Program (1993-2005). Subjects were assigned a lung cancer risk score by using a validated risk model. Starting with those at highest risk, subjects were interviewed by phone and invited to undergo low-dose CT between March 2013 and October 2016. Subjects with a diagnosis of lung cancer and those who had died of lung cancer were determined. Descriptive statistics were used to summarize data. The independent samples t test and Fisher exact test were used to compare age, sex, and risk scores. Results A total of 327 study participants were contacted, and 200 subjects participated in this study. The average age was 74 years (range, 57-88 years), and the median time since previous CT was 7 years. The incidence rate of developing lung cancer during the next 6 years was estimated at 5.6%. The period prevalence of lung cancer was 20.8% (new and preexisting lung cancer, 68 of total cohort of 327). The detection rate of low-dose CT was 7% (14 of 200 subjects). Of the 14 screening-detected cancers, 12 were stage I or II. Conclusion High-risk individuals have a high incidence of lung cancer after previous negative lung cancer screening. Early-stage lung cancer can be successfully detected in older high-risk individuals. © RSNA, 2018 Online supplemental material is available for this article.


Some Information Geometric Aspects of Cyber Security by Face Recognition.
Secure user access to devices and datasets is widely enabled by fingerprint or face recognition. Organization of the necessarily large secure digital object datasets, with objects having content that may consist of images, text, video or audio, involves efficient classification and feature retrieval processing. This usually will require multidimensional methods applicable to data that is represented through a family of probability distributions. Then information geometry is an appropriate context in which to provide for such analytic work, whether with maximum likelihood fitted distributions or empirical frequency distributions. The important provision is of a natural geometric measure structure on families of probability distributions by representing them as Riemannian manifolds. Then the distributions are points lying in this geometrical manifold, different features can be identified and dissimilarities computed, so that neighbourhoods of objects nearby a given example object can be constructed. This can reveal clustering and projections onto smaller eigen-subspaces which can make comparisons easier to interpret. Geodesic distances can be used as a natural dissimilarity metric applied over data described by probability distributions. Exploring this property, we propose a new face recognition method which scores dissimilarities between face images by multiplying geodesic distance approximations between 3-variate RGB Gaussians representative of colour face images, and also obtaining joint probabilities. The experimental results show that this new method is more successful in recognition rates than published comparative state-of-the-art methods.


Health of grey nomads: On the move and under the health sector radar.
Grey nomads - older people driving long distances recreationally and staying in caravans, tents or motor homes - are common on Australian highways. Although grey nomads report many benefits from their travels, there is anecdotal evidence that they impose a significant burden on rural/remote health services, including general practitioners, pharmacists and hospitals. There have been calls for better resourcing and service provision, but little reference to solid evidence on which to base this. This literature review is the first to integrate existing evidence for a health audience. Australia. Narrative literature search and synthesis. There is very little published information about the health and health service utilisation of grey nomads, and almost none in the medical literature. One key exception, a survey at a caravan park in the Kimberley region, found that, like other older Australians, many grey nomads have chronic diseases, and they have high rates of medication use. However, other studies have found that they generally view themselves as relatively healthy. There is some evidence of inadequate preparation for travelling. Issues include lack of health summaries, inadequate medication supplies and suboptimal vaccination. Some experience emergencies, sometimes resulting in hospital admissions. Overall, they place a poorly documented burden on rural/remote services. There is a need for further research on the health of grey nomads, their use of self-care strategies, and their uptake of health services both on the road and at home, to inform the provision of health services and optimise their well-being and health care utilisation.


Differential down-regulation of protein kinase C selectively affects IgE-dependent exocytosis and inositol trisphosphate formation.
Short-term treatment of rat basophilic leukaemia (RBL-2H3) cells with the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA) activates protein kinase C (PKC) and results in the inhibition of the IgE-dependent formation of inositol phosphates, but in the potentiation of serotonin secretion. Long-term treatment with TPA, which depletes the cells of their endogenous PKC, eliminates both Ca2(+)-ionophore- and TPA- as well as IgE-dependent secretion, but it potentiates by 1.7-fold IgE-induced inositol phosphate formation. Taken together, these observations strongly suggest that the dual actions of TPA on IgE-dependent responses are both mediated by PKC. The opposing effects of TPA are differentially down-regulated. Following TPA treatment, the rate by which the cells lose their ability to undergo exocytosis is faster than the rate at which inhibition of inositol phosphates formation is relieved and their production potentiated. In addition, both processes show different sensitivities to inhibitors of PKC action. Whereas IgE-dependent secretion is completely blocked by the PKC inhibitors K252a, H-7 and sphingosine [concns. causing 50% inhibition (IC50 values) = 25 ng/ml 80 microns and 30 microns respectively], these inhibitors do not relieve inhibition of inositol phosphate formation by TPA, nor do they potentiate this response. These results may imply that the bidirectional control exerted by PKC on IgE-dependent responses is mediated by its different isoenzymes.


Improvement in Functional Outcomes After Elective Symptomatic Orthopaedic Implant Removal.
The relative indications for removing symptomatic implants after osseous healing are not fully agreed on. The purpose of this study was to (1) determine whether patients showed improvement in functional outcomes after the removal of symptomatic orthopaedic implants, (2) compare the outcomes between upper and lower extremity implant removal, and (3) determine the rate of implant removal complications. A prospective study was conducted between 2013 and 2016. Patients completed a Short Musculoskeletal Function Assessment outcome questionnaire before implant removal and at the 6-month follow-up. Demographic data were stratified and compared between upper and lower extremity groups and between preimplant removal and 6-month postremoval. Of the 119 patients included in the study, 85 (71.4%) were lower extremity and 34 (28.6%) were upper extremity. Significant improvement after implant removal was seen in the dysfunction index (P ≤ 0.001), bother index (P ≤ 0.001), and daily activities domain (P ≤ 0.001). Depression or anxiety (P = 0.016) were statistically significant predictors for an improved Short Musculoskeletal Function Assessment dysfunction index score at 6 months. The complication rate was 10.1% (n=12) for the cohort. Implant removal in both the upper and lower extremity presented notable improvement in dysfunction. Complications that require surgical intervention are extremely rare.


[An overview of telehealth initiatives in Latin America].
This article aimed to systematize the views on telehealth in Latin America and to present the experience of building an instrument for monitoring the development of telehealth initiatives based on the reality of this region. A group was structured to coordinate telehealth efforts in Latin America, with members appointed by the ministries of health of 16 countries. Five thematic groups were also set up. Based on international experiences and focusing on the reality of telehealth in the continent, an instrument was created to monitor the development of telehealth in Latin America. Several countries have national telehealth projects: Brazil, Colombia, Ecuador, Mexico, Panama. Others are in the process of development and early deployment: Bolivia, Costa Rica, Cuba, El Salvador, Guatemala, Peru, Venezuela. The instrument described in the article, which is still being tested, proposes a characterization of countries according to their telehealth development stage: nonexistent, nascent, intermediate, advanced, and exemplary. Currently, important telehealth initiatives are already underway in Latin America.


Daytime sleepiness is independently associated with falls in older adults with dementia.
To examine whether elderly people with dementia have a higher prevalence of falls and sleep disturbances than those without dementia, and to determine the subjective sleep characteristics associated with falls in older adults with dementia. This was a cross-sectional, population-based study derived from the data in the 2009 Taiwan National Health Interview Survey. A total of 123 older adults with dementia (aged 65 years or older), and 246 older adults without dementia who were randomly selected from the database were included. The occurrence of falls and subjective sleep characteristics (e.g. sleep hours, insomnia symptoms, daytime sleepiness, difficulty in breathing during sleep and daytime naps) were evaluated using the responses to the survey questions. The prevalence of falls in older adults with dementia were approximately twofold higher than that for those without dementia (27.6% vs 15.3%, P = 0.006). Older adults with dementia had longer sleep hours, and increased daytime sleepiness, daytime naps and difficulty in breathing during sleep (all P < 0.05) than those without dementia. Among older adults with dementia, daytime sleepiness was the only sleep characteristic that was significantly correlated to an increased risk of falls (adjusted odds ratio 5.56, 95% confidence interval 1.95-15.91) despite controlling for possible risk factors. Older adults with dementia had a higher prevalence of falls and sleep disturbances than that observed for those without dementia. Daytime sleepiness was an independent risk factor of falls in elderly people, with dementia after accounting for a range of covariates. Geriatr Gerontol Int 2016; 16: 850-855.


Paradoxical dilation of the large cerebral arteries in hypocapnia in man.
By grouping patients who had carotid angiograms under unusually carefully monitored conditions it has been shown that hypocapnia is associated with vasodilation at low blood pressure but not at high blood pressure. The mechanism is discussed in general terms and it is suggested that the hypocapnic vasodilation may be a response to cerebral hypoxia and may be transmitted via an intracerebral autonomic pathway. Clinical and angiographical diagnoses are given for 50 patients.


Thematic review series: patient-oriented research. Nutritional determinants of insulin resistance.
Interpreting the literature relating to the nutritional determinants of insulin resistance is complicated by the wide range of methods used to determine insulin sensitivity. Excess adiposity is unquestionably the most important determinant of insulin resistance, although the effect may be tempered by a relatively high proportion of lean body mass. Weight loss is associated with improved insulin sensitivity. Thus, diet-related factors that promote excessive energy intake may be regarded as promoters of insulin resistance. In the context of energy balance, diets characterized by high intakes of saturated fat and low intakes of dietary fiber are associated with reduced insulin sensitivity. Total fat intakes greater than the usually consumed range appear to promote insulin resistance, although the relative proportions of total fat and carbohydrate within the usual range appear unimportant. Monounsaturated fatty acids with a cis configuration and fiber-rich carbohydrate foods appear to be appropriate substitutes for saturated fatty acids and rapidly digested glycemic carbohydrates. In animal studies, n-3 unsaturated fatty acids have been shown to enhance insulin sensitivity and fructose and sucrose to increase insulin resistance. However, human data are limited. Large prospective studies currently being conducted should confirm the most appropriate macronutrient composition of diets for preventing and treating insulin resistance as well as establishing whether a range of candidate genes explains the variation in response to dietary change.


LBP, CD14, TLR4 and the murine innate immune response to a peritoneal Salmonella infection.
In mice, defense against an intraperitoneal Salmonella infection depends on a vigorous innate immune response. Mutations which lead to an inadequate early response to the pathogen thus identify genes involved in innate immunity. The best studied host resistance factor, NRAMP-1, is an endosomal membrane protein whose loss leads to an inability of the animals to hold the infection in check. However, innate defense against Salmonella is not restricted to mechanisms which directly attack the pathogen within macrophages. Here we have examined the contribution of the LBP, CD14 and TLR4 gene products to innate defense against Salmonella. To this end, we have generated mice which carry a wild-type allele of NRAMP-1, but which are deficient for the LBP, CD14 or TLR4 genes. Loss of any of these genes leads to a susceptibility to Salmonella as dramatic as that seen in animals lacking functional NRAMP-1 protein. This indicates that LBP, CD14 and TLR4 are all critical elements required in the proper induction of this innate defense system.


First Report of Taro vein chlorosis virus Infecting Taro (Colocasia esculenta) in the United States.
In March 2013, taro plants (Colocasia esculenta [L.] Schott cv. Iliuaua) with leaves displaying veinal chlorosis and necrosis were observed on the island of Molokai. These symptoms were similar to those of taro vein chlorosis, a disease of taro caused by Taro vein chlorosis virus (TaVCV; family Rhabdoviridae, genus Nucleorhabdovirus). To explore this possibility, RNA was isolated from both symptomatic and asymptomatic taro leaves using the NucleoSpin RNA II extraction kit (Macherey-Nagel, Bethlehem, PA) according to the provided protocol, except that RLT Buffer (Qiagen Inc., Valencia, CA) was used as the initial extraction buffer. The RNAs were converted to cDNA using random primers and MMLV-RT reverse transcriptase (Promega, Madison, WI). The cDNA underwent PCR assays using primer sets Pol2A1/Pol2A2 and Cap2A/Cap2B which target the RNA-dependent RNA polymerase (RdRp) and putative nucleocapsid genes of TaVCV, respectively (1). Amplification products of the correct size were obtained for both primer sets, and these underwent molecular cloning using pGEM-T Easy (Promega). Three clones were selected and their sequences determined by dye-terminator sequencing. After primer sequence removal, the Pol2A1/Pol2A2 product (952 bp; GenBank Accession No. KF921085) and Cap2A/Cap2B product (1,050 bp; KF921086) were found to be 79 and 84% identical to a Fijian strain of TaVCV (AY674964), respectively. Samples from 328 plants with and without taro vein chlorosis symptoms were collected from 35 sites on five of the Hawaiian islands and assayed for TaVCV using the Pol2A1/Pol2A2 primer set as described above. The incidence of TaVCV in these samples was 21.6%, with positive samples coming from each island. Although a very strong association between symptoms and the presence of TaVCV was observed, eight asymptomatic plants were also positive, suggesting the detection assay was able to detect the virus before the onset of symptoms. Conversely, three symptomatic plants were found to be negative, suggesting the Pol2A1/Pol2A2 PCR assay might not detect all strains of TaVCV in Hawaii. A digoxygenin-labeled probe (Roche Applied Science, Indianapolis, IN) derived from the Pol2A1/Pol2A2 amplification product of one sample hybridized with the cDNA of only four of nine TaVCV-infected samples collected from three different islands in a dot-blot hybridization assay performed at high stringency. This probe did not hybridize with the cDNA of five TaVCV-negative samples. TaVCV exhibits a great deal of genetic diversity in the South Pacific nations where it is found; nucleotide divergence of up to 27% in regions of the RdRp gene has been reported (1). The high genetic divergence between the TaVCV isolate characterized in Hawaii and the TaVCV accession in GenBank, as well as the dot blot hybridization assay results support this observation. The widespread distribution of TaVCV in Hawaii suggests it is not a recent introduction. However, the common practice of farmers sharing taro propagules has likely accelerated its spread. An arthropod vector of TaVCV has yet to be identified, so it is unknown whether natural spread is also occurring in Hawaii. Taro has both economic and cultural importance to Hawaii. These findings, representing the first detection of TaVCV in Hawaii and the United States, illustrate the need to develop virus-free germplasm for local, national, and international distribution of this important staple crop. Reference: (1) P. Revill et al. J. Gen Virol. 86:491, 2005.


Cross-cultural adaptation and validation of the Kerlan-Jobe Orthopaedic Clinic shoulder and elbow score in Finnish-speaking overhead athletes.
The Kerlan-Jobe Orthopaedic Clinic Shoulder and Elbow score (KJOC) is developed to evaluate the shoulder and elbow function in overhead athletes. To date, the score has not been adapted into Finnish language. The aim of this study was to perform a cross-cultural adaptation of the Kerlan-Jobe Orthopaedic Clinic Shoulder and Elbow score (KJOC) into Finnish language and evaluate its validity, reliability, and responsiveness in overhead athletes. Forward-backward translation method was followed in the cross-cultural adaptation process. Subsequently, 114 overhead athletes (52 males, 62 females, mean age 18.1 ± 2.8 years) completed the Finnish version of KJOC score, Disabilities of the Arm, Shoulder and Hand (DASH), American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form (ASES) and RAND-36 to assess validity of the KJOC score. To evaluate reliability and responsiveness, the participants filled in the KJOC score 16 days and eight months after the first data collection. Validity, reliability, and responsiveness of the Finnish KJOC score were statistically tested. Minor modifications were made during the cross-cultural translation and adaptation process, which were related to culture specific terminology in sports and agreed by an expert committee. Construct validity of the KJOC score was moderate to high, based on the correlations with DASH (r = - 0.757); DASH sports module (r = - 0.667); ASES (r = 0.559); and RAND-36 (r = 0.397) questionnaires. Finnish KJOC score showed excellent internal consistency (α = 0.92) and good test-retest reliability (2-way mixed-effects model ICC = 0.77) with acceptable measurement error level (SEM 5.5; MDC 15.1). Ceiling effect was detected for asymptomatic athletes in each item (23.2-61.1%), and for symptomatic athletes in item 5 (47.4%). Responsiveness of the Finnish KJOC score could not be confirmed due to conflicting follow-up results. The Finnish KJOC score was found to be a valid and reliable questionnaire measuring the self-reported upper arm status in Finnish-speaking overhead athletes.


The effect of pomegranate seed oil on human health, especially epidemiology of polycystic ovary syndrome; a systematic review.
Polycystic ovary syndrome is the most common endocrine disorder in women. Today, medicinal plants have been considered by women, especially in the reproductive and pregnancy ages. Multiple drug treatments and the length of the treatment period often lead to incomplete treatment by patients. Therefore, due to the side effects of chemical drugs, this study was conducted to assess investigate the effect of pomegranate seed oil on polycystic ovary syndrome. The prevalence of polycystic ovary syndrome is increasing by 15 to 20% and clinically includes oligomenorrhea or amenorrhea, hirsutism, and often infertility. Databases such as Cochran library, Medline, PubMed, SID, and Science Direct were used to access the related articles. To collect the required information, first, the articles that had one of the keywords of medicinal plants, polycystic ovary syndrome, plant, pomegranate extract, and menstrual irregularities in their text were searched in databases. All studies from 1985 to 2021 are included in the study. Conjugated linolenic acid (CLN) is a group of geometric and positional isomers of linolenic acid in which double bonds are conjugated. CLN has been reported to have a very strong cytotoxic effect on tissue tumor cells in the body, preventing cancer, reducing the accumulation of triacylglycerol in the liver, polycystic ovary syndrome, and LDL cholesterol in the blood. So far, seven CLN isomers have been identified, including ponic acid in pomegranate seed oil. Conjugated linoleic acid (CLA) is a group of situational and geometric isomers of linoleic acid in which double bonds are conjugated. The positive effects of the two main CLA isomers (cis-9, trans-11, and trans-10, cis-12) include inhibiting the growth of cancer, reducing the risk of atherosclerosis, and reducing body fat.


Tomato roots secrete tomatine to modulate the bacterial assemblage of the rhizosphere.
Saponins are the group of plant specialized metabolites which are widely distributed in angiosperm plants and have various biological activities. The present study focused on α-tomatine, a major saponin present in tissues of tomato (Solanum lycopersicum) plants. α-Tomatine is responsible for defense against plant pathogens and herbivores, but its biological function in the rhizosphere remains unknown. Secretion of tomatine was higher at the early growth than the green-fruit stage in hydroponically grown plants, and the concentration of tomatine in the rhizosphere of field-grown plants was higher than that of the bulk soil at all growth stages. The effects of tomatine and its aglycone tomatidine on the bacterial communities in the soil were evaluated in vitro, revealing that both compounds influenced the microbiome in a concentration-dependent manner. Numerous bacterial families were influenced in tomatine/tomatidine-treated soil as well as in the tomato rhizosphere. Sphingomonadaceae species, which are commonly observed and enriched in tomato rhizospheres in the fields, were also enriched in tomatine- and tomatidine-treated soils. Moreover, a jasmonate-responsive ETHYLENE RESPONSE FACTOR 4 mutant associated with low tomatine production caused the root-associated bacterial communities to change with a reduced abundance of Sphingomonadaceae. Taken together, our results highlight the role of tomatine in shaping the bacterial communities of the rhizosphere and suggest additional functions of tomatine in belowground biological communication.


Effect of prenatal counselling on compliance and outcomes of teenage pregnancy.
To evaluate the effect of prenatal counselling on compliance for health promotion and pregnancy outcomes we conducted an experimental randomized control study on a sample of 86 teenage pregnant women attending the maternal and child health centre in Elkhosos village, Egypt. Data were collected pre-counselling, post-counselling and after delivery. At the post test, women in the study (counselling) group showed statistically significantly greater knowledge and compliance of health promotion (P < 0.001) than women in the control group. In the study group, 90.7% were full term at labour compared with 41.9% in the control group; 88.4% of the women in the study group had normal vaginal delivery compared with 76.7% of those in the control group. The health condition in 90.7% of the study group neonates was classified as good compared with only 46.5% in the control group. Only 9.3% of the study group babies had low birth weight compared with 32.6% of the control group babies (P = 0.008).


Ampicillin resistance in Haemophilus influenzae.
Fourteen out of 150 (9.3%) consecutive strains of Haemophilus influenzae isolated on culture of sputum in the Bacteriology Department, Belfast City Hospital, during 1982/83 were found to be ampicillin-resistant (beta-lactamase-producing). Susceptibility testing to other antibiotics of these ampicillin-resistant strains showed that cefuroxime, cefotaxime, gentamicin, and amoxycillin with clavulanic acid were reliable alternatives. Other useful alternatives included tetracycline, trimethoprim and co-trimoxazole. Erythromycin was of limited usefulness.


Increased efficiency in selective elimination of leukemia cells by a combination of a stable derivative of cyclophosphamide and a human B-cell-specific immunotoxin containing pokeweed antiviral protein.
Leukemia cells were mixed with normal human bone marrow cells to simulate bone marrow from leukemia patients; the mixture was then treated with a combination of stabilized derivative of cyclophosphamide [Mafosfamide (ASTA Z 7557)] and pokeweed antiviral protein-containing immunotoxin. The ability of this protocol for selective elimination of B-ALL cells was evaluated by clonogenic assay. The monoclonal antibody (B43) portion of the immunotoxin was directed against human B-cells and was linked to pokeweed antiviral protein by a disulfide bond. The combination of ASTA Z 7557 and immunotoxin was superior to either ASTA Z 7557 or the immunotoxin alone and produced nearly 7 logs of elimination of leukemia cells from the cell mixtures. About 5 logs of contaminating tumor cells were eliminated from a 200-fold excess of normal marrow under conditions where fewer than 50% of pluripotent stem cells were lost. Moreover, this manipulation did not inhibit subsequent production of pluripotent stem cells in long-term bone marrow cultures, indicating that the more primitive progenitors were not harmed.


A rare case of t(11;22) in a mantle cell lymphoma like B-cell neoplasia resulting in a fusion of IGL and CCND1: case report.
The chromosomal translocation (11;14)(q13;q32) rearranging the locus for cyclin D1 (CCND1) to that of the immunoglobulin heavy chain (IGH) can be found in virtually all cases of mantle cell lymphoma (MCL), while other CCND1 translocations are extremely rare. As CCND1 overexpression and activation is a hallmark of MCL it is regarded as a central biological mechanism in the development and maintenance of this disease.Here we present a patient initially diagnosed with chronic lymphocytic leukemia (CLL) where chromosome banding analysis revealed, among other aberrations, a translocation (11;22)(q13;q11.2). We show by fluorescence in situ hybridization (FISH) analysis that on chromosome 22 the immunoglobulin light chain lambda (IGL) is involved in this cytogenetic aberration. Additionally, we demonstrate the resulting overexpression of CCND1 on the RNA and protein level, thereby consolidating the new diagnosis of a MCL-like B-cell neoplasia. Summing up, we described a rare case of t(11;22)(q13;q11.2) in a MCL-like neoplasia and showed that this aberration leads to an overexpression of CCND1 which is regarded as a key biological feature in MCL. This case underlines the importance of cytogenetic analyses especially in atypical cases of B cell lymphomas.


Indigenous perinatal and neonatal outcomes: a time for preventive strategies.
Pregnancy outcomes for Indigenous mothers and babies have improved, but marked disparities remain between Indigenous and non-Indigenous women. Many contributors to these disparities such as smoking, alcohol use, poor nutrition, infection, teenage pregnancy and stress are preventable or modifiable particularly if addressed prior to pregnancy. It is suggested that we expand our reproductive health research, education and care to a life course approach beginning in early adolescence.


Building Chronic Kidney Disease Clinical Practice Guidelines Using the openEHR Guideline Definition Language.
As a result of the disease's high prevalence, chronic kidney disease (CKD) has become a global public health problem. A clinical decision support system that integrates with computer-interpretable guidelines (CIGs) should improve clinical outcomes and help to ensure patient safety. The openEHR guideline definition language (GDL) is a formal language used to represent CIGs. This study explores the feasibility of using a GDL approach for CKD; it also attempts to identify any potential gaps between the ideal concept and reality. Using the Kidney Disease Improving Global Outcomes (KDIGO) anemia guideline as material, we designed a development workflow in order to establish a series of GDL guidelines. Focus group discussions were conducted in order to identify important issues related to GDL implementation. Ten GDL guidelines and 37 archetypes were established using the KDIGO guideline document. For the focus group discussions, 16 clinicians and 22 IT experts were recruited and their perceptions, opinions and attitudes towards the GDL approach were explored. Both groups provided positive feedback regarding the GDL approach, but raised various concerns about GDL implementation. Based on the findings of this study, we identified some potential gaps that might exist during implementation between the GDL concept and reality. Three directions remain to be investigated in the future. Two of them are related to the openEHR GDL approach. Firstly, there is a need for the editing tool to be made more sophisticated. Secondly, there needs to be integration of the present approach into non openEHR-based hospital information systems. The last direction focuses on the applicability of guidelines and involves developing a method to resolve any conflicts that occur with insurance payment regulations.


The amyloid precursor protein modulates α2A-adrenergic receptor endocytosis and signaling through disrupting arrestin 3 recruitment.
The amyloid precursor protein (APP) has long been appreciated for its role in Alzheimer's disease (AD) pathology. However, less is known about the physiologic function of APP outside of AD. Particularly, whether and how APP may regulate functions of cell surface receptors, including GPCRs, remains largely unclear. In this study, we identified a novel direct interaction between APP and the α2A-adrenergic receptor (α2AAR) that occurs at the intracellular domains of both proteins. The APP interaction with α2AAR is promoted by agonist stimulation and competes with arrestin 3 binding to the receptor. Consequently, the presence of APP attenuates α2AAR internalization and desensitization, which are arrestin-dependent processes. Furthermore, in neuroblastoma neuro-2A cells and primary superior cervical ganglion neurons, where APP is highly expressed, the lack of APP leads to a dramatic increase in plasma membrane recruitment of endogenous arrestin 3 following α2AAR activation. Concomitantly, agonist-induced internalization of α2AAR is significantly enhanced in these neuronal cells. Our study provided the first evidence that APP fine tunes GPCR signaling and trafficking. Given the important role of α2AAR in controlling norepinephrine release and response, this novel regulation of α2AAR by APP may have an impact on modulation of noradrenergic activity and sympathetic tone.-Zhang, F., Gannon, M., Chen, Y., Zhou, L., Jiao, K., Wang, Q. The amyloid precursor protein modulates α2A-adrenergic receptor endocytosis and signaling through disrupting arrestin 3 recruitment.


Thiophilic adsorption chromatography: purification of Equ c2 and Equ c3, two horse allergens from horse sweat.
Purification of two allergens from horse (Equus caballus) sweat, Equ c2 and Equ c3, by means of salt-promoted chromatography on a "thiophilic" (T-gel) adsorbent is described. Immobilization of these proteins was found to be dependent on the presence of water-structure-forming salts where the ammonium sulphate concentration in the equilibration buffer was 2 M. Equ c2 showed higher affinity towards the thiophilic matrix than Equ c3. Their molecular mass (Mr) values established by SDS-polyacrylamide gel electrophoresis were for Equ c2 approximately 17,000 and for Equ c3 approximately 16,000, and both proteins showed a low isoelectric point of approximately 3.8. Their allergenic properties were also investigated using sera from horse-sensitized patients, where it was demonstrated that these proteins exhibited an IgE antibody binding capacity. In this report we show the broad potential applications of thiophilic adsorption chromatography for the efficient purification of allergens.


Timing of prepubertal androgen administration may have different effects on future fertility as well as penile size in normal male rats.
To investigate the effects of androgen administration at different periods of prepubertal life on penile size and potential fertility in hormonally normal rats. Eighty Sprague-Dawley rats were divided into 4 groups; group 1 received weekly injections of testosterone enanthate (8 mg/100 g) at 1-3 weeks group 2 at 3-5 weeks, group 3 at 1-5 weeks, and group 4 was control (n = 20 each). Animals were killed at age 60 days. Penile length, penile, testicular, and epididymal weight, testicular fertility index, serum follicular stimulating hormone, luteinizing hormone, and testosterone levels were measured and quantitative real time polymerase chain reaction of penile androgen receptor messenger ribonucleic acids was performed. Penile length in the 3-5-week injection group was significantly longer than controls (41.18 vs 39.13 mm, P = .011), and it was smaller than controls in the 1-3 week injection group (37.24 vs 39.13 mm, P = .020). The penile wet weight showed a similar pattern to stretched penile length; however, statistical significance was not found. Testicular weight was significantly less in the testosterone injection group than controls (1.79, 2.16, 2.24, and 2.78 g in groups 1-4, respectively) as well as the epididymal weight (0.48, 0.42, 0.59, and 0.69 in groups 1-4, respectively). The mean tubular diameter and germ cell count were significantly reduced in the testosterone treated group. Total penile androgen receptor messenger ribonucleic acid level was significantly lower in group 3 as compared with controls. Testosterone administered during early prepubertal life resulted in smaller penis than controls, as well as having an adverse effect on testicular development which can jeopardize potential fertility.


Health Promotion Practice Among Older Persons: A Nordic Multi-Professional Focus Group Study Exploring what It Is and How It Could be Achieved.
The growing ageing population in the Nordic region calls for increased focus on health promotion work. To enhance multi-professional understanding and further develop strategies for promoting healthy ageing, it is vital to consider the perspectives of those working with health promotion. The aim of this study was to explore a wide spectrum of practitioners' experiences of community-level health promotion targeting older adults in Finland and Sweden. Nine focus group interviews (34 informants) were conducted in 2019-2020. "Seeing the person" emerged as the ideal for health promotion targeting older adults, but this ideal was not always realized in current practice. Barriers related to organizational structures and the practitioner role were identified. However, work methods connected to user involvement and technology-based tools were considered key facilitators, enabling tailored health promotion initiatives.


Pediatric sleep questionnaire: prediction of sleep apnea and outcomes.
To further validate a questionnaire about symptoms of childhood obstructive sleep apnea (OSA) and to compare the questionnaire with polysomnography in their ability to predict outcomes of adenotonsillectomy. Retrospective analysis of data from a longitudinal study. University-based sleep disorders laboratory. The Washtenaw County Adenotonsillectomy Cohort, comprising 105 children aged 5.0 to 12.9 years at entry. Intervention Parents completed the 22-item Sleep-Related Breathing Disorder (SRBD) scale of the Pediatric Sleep Questionnaire, and children underwent polysomnography before and 1 year after clinically indicated adenotonsillectomy (n = 78, usually for suspected OSA) or unrelated surgical care (n = 27). Findings from commonly used hyperactivity ratings, attention tests, and sleepiness tests. At baseline, a high SRBD scale score (1 SD above the mean) predicted an approximately 3-fold increased risk of OSA on polysomnography (odds ratio, 2.80; 95% confidence interval, 1.68-4.68). One year later, OSA and symptoms had largely resolved, but a high SRBD score still predicted an approximately 2-fold increased risk of residual OSA on polysomnography (odds ratio, 1.89; 95% confidence interval, 1.13-3.18). Compared with several standard polysomnographic measures of OSA, the baseline SRBD scale better predicted initial hyperactivity ratings and 1-year improvement, similarly predicted sleepiness and its improvement, and similarly failed to predict attention deficit or its improvement. The SRBD scale predicts polysomnographic results to an extent useful for research but not reliable enough for most individual patients. However, the SRBD scale may predict OSA-related neurobehavioral morbidity and its response to adenotonsillectomy as well or better than does polysomnography.


Electrical charging effects on the sliding friction of a model nano-confined ionic liquid.
Recent measurements suggest the possibility to exploit ionic liquids (ILs) as smart lubricants for nano-contacts, tuning their tribological and rheological properties by charging the sliding interfaces. Following our earlier theoretical study of charging effects on nanoscale confinement and squeezout of a model IL, we present here molecular dynamics simulations of the frictional and lubrication properties of that model under charging conditions. First, we describe the case when two equally charged plates slide while being held together to a confinement distance of a few molecular layers. The shear sliding stress is found to rise strongly and discontinuously as the number of IL layers decreases stepwise. However, the shear stress shows, within each given number of layers, only a weak dependence upon the precise value of the normal load, a result in agreement with data extracted from recent experiments. We subsequently describe the case of opposite charging of the sliding plates and follow the shear stress when the charging is slowly and adiabatically reversed in the course of time, under fixed load. Despite the fixed load, the number and structure of the confined IL layers change with changing charge, and that in turn drives strong friction variations. The latter involves first of all charging-induced freezing of the IL film, followed by a discharging-induced melting, both made possible by the nanoscale confinement. Another mechanism for charging-induced frictional changes is a shift of the plane of maximum shear from mid-film to the plate-film interface, and vice versa. While these occurrences and results invariably depend upon the parameters of the model IL and upon its specific interaction with the plates, the present study helps identifying a variety of possible behavior, obtained under very simple assumptions, while connecting it to an underlying equilibrium thermodynamics picture.


The solution conformational features of two highly homologous antigenic peptides of foot-and-mouth disease virus serotype A, variant A and USA, correlate with their serological properties.
The solution structure of a peptide corresponding to the VP1 region 141-160 of foot-and-mouth disease virus (FMDV) serotype A variant USA has been studied by NMR and computer calculations and compared with the results from a study on a highly homologous peptide deriving from serotype A, variant A. The two peptides differ in their serological behavior and contain the immunodominant epitope of the virus which partly overlaps with its receptor binding region. Distance constraints, derived both from 2D and 3D homonuclear NMR and 2D-heteronuclear NMR experiments, were combined with DG calculations to yield 50 structures. After refinement through EM and restrained molecular dynamics simulations the selected structures shared several general features. In particular the 151-158 region was a helix in all cases while a large loop similar to that found in peptide A but comprising less residues and stabilized by an H-bond between the side chains of D147 and S150 was found in the majority of structures. A further loop, common to all structures, was identified around the RGD sequence (145-147). This was different from that found in the corresponding region of peptide A as were the conformations of the individual residues within the RGDX sequence. The different structural features shown by the two peptides were rationalized in terms of the S148 (peptide A) to F148 (peptide USA) mutation. The second mutation, that at position 153 (L in A, P in USA) did not appear to affect the structure of the peptide significantly although the different dimensions of the loop in the central region and the type of H-bond stabilizing it could be potentially ascribed to this second mutation. All criteria used pointed to different structural features for the two peptides consistent with their serological behaviour.


Do foot orthoses change lower limb muscle activity in flat-arched feet towards a pattern observed in normal-arched feet?
One of the hypothesised mechanisms by which foot orthoses obtain their clinical effect is by influencing muscle activity, however previous studies have reported highly variable findings. The aim of this study was to determine whether orthoses change muscle activity in people with flat-arched feet towards a pattern observed in people with normal-arched feet. Thirty young asymptomatic adults with flat-arched feet were recruited. Foot posture was classified using two clinical measurements and four skeletal alignment measurements from weight-bearing foot x-rays. Electromyographic activity was recorded while walking from tibialis posterior and peroneus longus via in-dwelling wire electrodes, and from tibialis anterior and medial gastrocnemius via surface electrodes. Four experimental conditions were assessed: (i) barefoot, (ii) shoe only, (iii) a heat-moulded (modified) prefabricated foot orthosis, and (iv) a 20-degree inverted-style customised foot orthosis. During the contact phase of gait, tibialis posterior electromyographic amplitude decreased significantly with the prefabricated orthosis (peak amplitude - 19% decrease, P=0.007; RMS amplitude--22% decrease, P=0.002) and the customised orthosis (peak amplitude--12% decrease, P<0.001, RMS amplitude--13% decrease, P=0.001), compared with the shoe-only condition. During the midstance/propulsive phase, peroneus longus electromyographic amplitude increased significantly with the prefabricated orthosis, compared with the shoe-only (peak amplitude--21% increase, P=0.024; RMS amplitude--24% increase, P=0.019) and customised orthosis conditions (peak amplitude--16% increase, P=0.028). The foot orthoses significantly altered tibialis posterior and peroneus longus electromyographic amplitude. However, only the modified prefabricated orthosis changed peroneus longus electromyographic amplitude towards a pattern observed with normal-arched feet. Otherwise, few differences were found between the modified prefabricated and customised orthoses. Further research is required to determine whether these changes in muscle function are associated with clinical outcomes.


Liver Abscess in a Pediatric Patient with Ulcerative Colitis: A Case Presentation.
Hepatic abscesses are an uncommon extra-intestinal manifestation of inflammatory bowel disease, the incidence of which has been estimated to be approximately 7 per 10,000 patients with inflammatory bowel disease. It is unclear whether patients with Crohn's disease or patients with ulcerative colitis (UC) are at higher risk of developing this complication. Based on case reports, most cases are found in Crohn's disease; however, a recent cohort study showed an increased risk in UC instead. Hepatic abscesses in the pediatric population are rare, and there have been no reported cases of hepatic abscesses in a pediatric patient with UC. We describe herein a pediatric patient with UC who developed hepatic abscesses and portal vein thrombosis. This patient also had an extended time in remission from his UC despite being off of immunosuppressive therapies, and we speculate on how his clinical course and treatment strategies may have contributed to this.


Web-based genome-wide association study identifies two novel loci and a substantial genetic component for Parkinson's disease.
Although the causes of Parkinson's disease (PD) are thought to be primarily environmental, recent studies suggest that a number of genes influence susceptibility. Using targeted case recruitment and online survey instruments, we conducted the largest case-control genome-wide association study (GWAS) of PD based on a single collection of individuals to date (3,426 cases and 29,624 controls). We discovered two novel, genome-wide significant associations with PD-rs6812193 near SCARB2 (p = 7.6 × 10(-10), OR = 0.84) and rs11868035 near SREBF1/RAI1 (p = 5.6 × 10(-8), OR = 0.85)-both replicated in an independent cohort. We also replicated 20 previously discovered genetic associations (including LRRK2, GBA, SNCA, MAPT, GAK, and the HLA region), providing support for our novel study design. Relying on a recently proposed method based on genome-wide sharing estimates between distantly related individuals, we estimated the heritability of PD to be at least 0.27. Finally, using sparse regression techniques, we constructed predictive models that account for 6%-7% of the total variance in liability and that suggest the presence of true associations just beyond genome-wide significance, as confirmed through both internal and external cross-validation. These results indicate a substantial, but by no means total, contribution of genetics underlying susceptibility to both early-onset and late-onset PD, suggesting that, despite the novel associations discovered here and elsewhere, the majority of the genetic component for Parkinson's disease remains to be discovered.


Capture, swallowing, and egestion of microplastics by a planktivorous juvenile fish.
Microplastics (<5 mm) have been found in many fish species, from most marine environments. However, the mechanisms underlying microplastic ingestion by fish are still unclear, although they are important to determine the pathway of microplastics along marine food webs. Here we conducted experiments in the laboratory to examine microplastic ingestion (capture and swallowing) and egestion by juveniles of the planktivorous palm ruff, Seriolella violacea (Centrolophidae). As expected, fish captured preferentially black microplastics, similar to food pellets, whereas microplastics of other colours (blue, translucent, and yellow) were mostly co-captured when floating close to food pellets. Microplastics captured without food were almost always spit out, and were only swallowed when they were mixed with food in the fish's mouth. Food probably produced a 'gustatory trap' that impeded the fish to discriminate and reject the microplastics. Most fish (93% of total) egested all the microplastics after 7 days, on average, and 49 days at most, substantially longer than food pellets (<2 days). No acute detrimental effects of microplastics on fish were observable, but potential sublethal effects of microplastics on the fish physiological and behavioural responses still need to be tested. This study highlights that visually-oriented planktivorous fish, many species of which are of commercial value and ecological importance within marine food webs, are susceptible to ingest microplastics resembling or floating close to their planktonic prey.