Keratin 8 is a scaffolding and regulatory protein of ERAD complexes.
Early recognition and enhanced degradation of misfolded proteins by the endoplasmic reticulum (ER) quality control and ER-associated degradation (ERAD) cause defective protein secretion and membrane targeting, as exemplified for Z-alpha-1-antitrypsin (Z-A1AT), responsible for alpha-1-antitrypsin deficiency (A1ATD) and F508del-CFTR (cystic fibrosis transmembrane conductance regulator) responsible for cystic fibrosis (CF). Prompted by our previous observation that decreasing Keratin 8 (K8) expression increased trafficking of F508del-CFTR to the plasma membrane, we investigated whether K8 impacts trafficking of soluble misfolded Z-A1AT protein. The subsequent goal of this study was to elucidate the mechanism underlying the K8-dependent regulation of protein trafficking, focusing on the ERAD pathway. The results show that diminishing K8 concentration in HeLa cells enhances secretion of both Z-A1AT and wild-type (WT) A1AT with a 13-fold and fourfold increase, respectively. K8 down-regulation triggers ER failure and cellular apoptosis when ER stress is jointly elicited by conditional expression of the µs heavy chains, as previously shown for Hrd1 knock-out. Simultaneous K8 silencing and Hrd1 knock-out did not show any synergistic effect, consistent with K8 acting in the Hrd1-governed ERAD step. Fractionation and co-immunoprecipitation experiments reveal that K8 is recruited to ERAD complexes containing Derlin2, Sel1 and Hrd1 proteins upon expression of Z/WT-A1AT and F508del-CFTR. Treatment of the cells with c407, a small molecule inhibiting K8 interaction, decreases K8 and Derlin2 recruitment to high-order ERAD complexes. This was associated with increased Z-A1AT secretion in both HeLa and Z-homozygous A1ATD patients' respiratory cells. Overall, we provide evidence that K8 acts as an ERAD modulator. It may play a scaffolding protein role for early-stage ERAD complexes, regulating Hrd1-governed retrotranslocation initiation/ubiquitination processes. Targeting K8-containing ERAD complexes is an attractive strategy for the pharmacotherapy of A1ATD.


Effects of longitudinal maternal glucose control on infants of diabetic mothers.
Between 1980 and 1987, 45 pregnant women with diabetes mellitus who required insulin therapy were delivered at Kagoshima Municipal Hospital. The perinatal mortality rate in the present study was zero. Twelve infants were large for gestational age, ten were small for gestational age, and 23 were appropriate for gestational age. Tight maternal glucose control (fasting values of less than 100mg/dl and 2 hours post-prandial values of less than 120mg/dl) obtained before 32 weeks of gestation significantly decreased the incidence of large for gestational age infants. However, longitudinal control patterns of maternal glucose during pregnancy have little effect on the incidence of small for gestational age infants and neonatal complications. The former was more closely related to maternal vascular complications. Congenital malformations were found in two cases.


The actions of peppermint oil and menthol on calcium channel dependent processes in intestinal, neuronal and cardiac preparations.
The activities of menthol and peppermint oil were determined in guinea-pig ileal smooth muscle, in rat and guinea-pig atrial and papillary muscle, in rat brain synaptosomes and in chick retinal neurones by pharmacological 45Ca2+ uptake and radioligand binding assays. Menthol is a major constituent of peppermint oil and is approximately twice as potent as peppermint oil as an inhibitor of K+ depolarization-induced and electrically stimulated responses in ileum and electrically stimulated atrial and papillary muscles. IC50 values in the ileal preparation ranged from 7.7 to 28.1 micrograms ml-1 and in the cardiac preparations from 10.1 to 68.5 micrograms ml-1. Similar potencies were demonstrated against K+ depolarization-induced 45Ca2+ uptake in synaptosomes and against K+ depolarization and Bay K 8644-induced uptake in chick retinal neurons. IC50 values for menthol inhibition of K+ and Bay K 8644 responses in the retinal neurons were 1.1 x 10(-4) M (17.2 micrograms ml-1) and 1.75 x 10(-4) M (26.6 micrograms ml-1), respectively, and for peppermint oil were 20.3 and 41.7 micrograms ml-1 respectively. Both menthol and peppermint oil inhibited specific [3H]nitrendipine and [3H]PN 200-110 binding to smooth and cardiac muscle and neuronal preparations with potencies comparable to, but slightly lower than, those measured in the pharmacological and 45Ca2+ uptake experiments. Binding of menthol and peppermint oil, studied at 78 micrograms ml-1, was competitive against [3H]nitrendipine in both smooth muscle and synaptosome preparations. The data indicate that both menthol and peppermint oil exert Ca2+ channel blocking properties which may underlie their use in irritable bowel syndrome. Ca2+ channel antagonism may not be the only pharmacological effect of menthol and peppermint oil contributing to intestinal smooth muscle relaxation.


Selective neuronal damage and borderzone infarction in carotid artery occlusive disease: a 11C-flumazenil PET study.
The pathogenesis of selective neuronal damage in internal carotid artery (ICA) occlusive disease is unclear. Imaging of the central-type benzodiazepine receptor (BZR), which is expressed by most cortical neurons, provides information on the neuronal alterations induced by ischemia in vivo. Hemodynamic ischemia due to ICA occlusive disease may cause not only borderzone infarction but also selective neuronal damage beyond the regions of infarcts, which may be detected by a decrease in BZR in the normal-appearing cerebral cortex. The purpose of this study was to determine whether selective neuronal damage is associated with borderzone infarction in ICA occlusive disease. We measured BZR using PET and 11C-flumazenil in 62 nondisabled patients with ICA steno-occlusive lesions in the chronic stage. Flumazenil binding potential (BP) was calculated using the dynamic data and the reference tissue model. The infarcts on MRI-which were categorized as territorial, borderzone (external or internal), striatocapsular, lacunar, and other white matter infarcts-were correlated with the mean cerebral/cerebellar cortical BP ratio in the hemisphere with ICA occlusive disease. Patients with borderzone infarction (n=18) had a significantly decreased flumazenil BP ratio in the hemisphere with ICA occlusive disease compared with patients without borderzone infarction (n=44) and healthy control subjects (n=10). Multivariate analysis showed that external borderzone infarction was an independent predictor of the decreased flumazenil BP ratio. In ICA occlusive disease, selective neuronal damage demonstrated as decreased BZR is associated with borderzone infarction, suggesting that hemodynamic ischemia leading to borderzone infarction may cause selective neuronal damage beyond the regions of infarcts in the chronic stage.


Family caregiving of persons living with HIV/AIDS in Thailand: caregiver burden, an outcome measure.
The present paper provides an initial picture of HIV/AIDS-affected families. It is evident that families play a major role of support for HIV/AIDS patients in Thai society. Caregiver burden is one of the patient-related outcomes, which is the most common outcome measure in caregiver research. The demands on the family caregivers of these patients are enormous and need to be addressed. The determinants that are associated with caregiver burden such as caregiver characteristics, patient characteristics and social stigma are important for nurses to minimize the burden of care so that appropriate interventions can be developed for persons with HIV/AIDS and family members who share the work of managing their care at home.


The significance of rotation in fracture-separation of the articular pillar of a lower cervical vertebra. A clinical and cadaveric study.
We report 13 fracture-separations of an articular pillar at the lower cervical spine in 12 patients. There were 9 men and 3 women with a mean age at injury of 32 years, with involvement of C4, C5 and C6 vertebrae. Neurological symptoms were present in 9 patients, 2 were classified as ASIA A and 7 as ASIA D. The average magnitude of rotation of the articular pillar was 24 degrees (10 degrees-36 degrees). 4 patients with neurologic deficit and a rotated articular pillar of more than 25 degrees were operated on, while 8 patients, 3 of which had a rotation of more than 25 degrees, had closed treatment. Patients were followed from 8 months to 15 years (mean 9 years). Patients who had closed treatment and/or with a rotated fractured articular pillar of more than 25 degrees had less satisfactory results. This observation was affirmed by cadaveric studies which showed that rotation of more than 25 degrees is an additional factor of instability in a fractured articular pillar.


Attenuation of acetylcholine activated potassium current (I KACh) by simvastatin, not pravastatin in mouse atrial cardiomyocyte: possible atrial fibrillation preventing effects of statin.
Statins, 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitors, are associated with the prevention of atrial fibrillation (AF) by pleiotropic effects. Recent clinical trial studies have demonstrated conflicting results on anti-arrhythmia between lipophilic and hydrophilic statins. However, the underlying mechanisms responsible for anti-arrhythmogenic effects of statins are largely unexplored. In this study, we evaluated the different roles of lipophilic and hydrophilic statins (simvastatin and pravastatin, respectively) in acetylcholine (100 µM)-activated K+ current (IKACh, recorded by nystatin-perforated whole cell patch clamp technique) which are important for AF initiation and maintenance in mouse atrial cardiomyocytes. Our results showed that simvastatin (1-10 µM) inhibited both peak and quasi-steady-state IKACh in a dose-dependent manner. In contrast, pravastatin (10 µM) had no effect on IKACh. Supplementation of substrates for the synthesis of cholesterol (mevalonate, geranylgeranyl pyrophosphate or farnesyl pyrophosphate) did not reverse the effect of simvastatin on IKACh, suggesting a cholesterol-independent effect on IKACh. Furthermore, supplementation of phosphatidylinositol 4,5-bisphosphate, extracellular perfusion of phospholipase C inhibitor or a protein kinase C (PKC) inhibitor had no effect on the inhibitory activity of simvastatin on IKACh. Simvastatin also inhibits adenosine activated IKACh, however, simvastatin does not inhibit IKACh after activated by intracellular loading of GTP gamma S. Importantly, shortening of the action potential duration by acetylcholine was restored by simvastatin but not by pravastatin. Together, these findings demonstrate that lipophilic statins but not hydrophilic statins attenuate IKACh in atrial cardiomyocytes via a mechanism that is independent of cholesterol synthesis or PKC pathway, but may be via the blockade of acetylcholine binding site. Our results may provide important background information for the use of statins in patients with AF.


Growth hormone, IGF-I, and exercise effects on non-weight-bearing fast muscles of hypophysectomized rats.
The effects of growth hormone (GH) or insulin-like growth factor I (IGF-I) with or without exercise (ladder climbing) in countering the effects of unweighting on fast muscles of hypophysectomized rats during 10 days of hindlimb suspension were determined. Compared with untreated suspended rats, muscle weights were 16-29% larger in GH-treated and 5-15% larger in IGF-I-treated suspended rats. Exercise alone had no effect on muscle weights. Compared with ambulatory control, the medial gastrocnemius weight in suspended, exercised rats was larger after GH treatment and maintained with IGF-I treatment. The combination of GH or IGF-I plus exercise in suspended rats resulted in an increase in size of each predominant fiber type, i.e., types I, I + IIa and IIa + IIx, in the medial gastrocnemius compared with untreated suspended rats. Normal ambulation or exercise during suspension increased the proportion of fibers expressing embryonic myosin heavy chain in hypophysectomized rats. The phenotype of the medial gastrocnemius was minimally affected by GH, IGF-I, and/or exercise. These results show that there is an IGF-I, as well as a GH, and exercise interactive effect in maintaining medial gastrocnemius fiber size in suspended hypophysectomized rats.


Teeth in the maxillary sinus--imaging and management.
To evaluate the images obtained by CT in diagnosis and treatment plan of teeth in the maxillary sinus. Twelve patients with teeth in the maxillary sinus were studied by plain film radiography (PFR) and by CT with a dental software programme, which displays multiple panoramic and cross-sectional views of the mandible and maxilla. The three-dimensional morphology of the tooth, its inclination, proximity to the sinus wall, surgical planning and prediction of prognosis and complications were estimated on both PFR and on CT scans and scored. The radiographical features interpreted from PFR were fair or poorly diagnosed whereas CT provided excellent features. The surgical approach of choice was based on CT interpretation. CT is useful for diagnosis and treatment planning of teeth in the maxillary antrum.


Device- and Nondevice-Guided Slow Breathing to Reduce Blood Pressure in Patients with Hypertension: Protocol for a Systematic Review and Meta-analysis.
Physiotherapy can include both device-guided slow breathing (DGSB) and nondevice-guided slow breathing (NDGSB) in the treatment of systemic arterial hypertension. The aim of this study is to summarize the effects of DGSB on blood pressure levels of patients with hypertension based on the published literature to date. A systematic search of all published randomized controlled trials (RCTs) on the effects of device-guided and nondevice-guided slow breathing in patients with hypertension, without language restriction, was carried out up to a publication date of January 2020 in nine databases: PubMed/MEDLINE, Latin American and Caribbean Health Sciences Literature (LILACS), EMBASE, CENTRAL (Cochrane Central Register of Controlled Trials), Physiotherapy Evidence Database (PEDro), CINAHL (Cumulative Index to Nursing and Allied Health Literature), Scopus, Web of Science, and Livivo. Clinical trial records databases (ClinicalTrials.gov), and bases for the open gray literature, including Gray Literature Report and ProQuest Central (Citation, Abstract or Indexing, and Dissertations and Theses), were also searched for potentially eligible RCTs. The quality assessment of the included studies will be performed using the Cochrane Risk of Bias Tool for Randomized Trials. The overall quality of the evidence for each outcome will be assessed using the GRADE (Grading of Recommendations, Development and Evaluation) system. As of December 2021, the review was completed and all data from continuous variables referring to blood pressure values (mmHg) were synthesized. This systematic review will provide a summary of the current evidence on the effects of both DGSB and NDGSB on blood pressure levels. This information can contribute to decision-making by health professionals related to the use of these interventions in patients with hypertension. PROSPERO (Prospective International Register of Systematic Reviews) CRD42020147554; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=147554. RR1-10.2196/33579.


Treatment options for pilonidal sinus.
Pilonidal sinus disease often presents as a chronic problem in otherwise healthy hirsute men. A range of conservative techniques to surgical flaps have been employed to treat this condition. We review the literature on management of pilonidal sinus disease, including conservative and surgical techniques as well as novel laser therapy. Given current evidence, off-midline repair is now considered the standard of care; however, no statistically significant difference has been noted between primary versus secondary closure or between the Karydakis flap and Limberg flap. Treatment should be tailored to the individual, taking into account recurrent disease, recovery time, and the surgeon's comfort with the procedure.


Volitional control of heartbeat and its dependence on pallium.
It is believed that we cannot change our heart rhythm by will because the heartbeat is mainly controlled by the autonomic nervous system (ANS), which cannot be affected directly by subjective will. An experiment was designed to determine whether the heartbeat and ANS could be controlled by volition, and, if it is true, how they were controlled. It was demonstrated that the ANS could be partly controlled by volition. The volition, which tended to slow down the heartbeat, initiated synchronized activity in the medial prefrontal cortex, inhibited the sympathetic system, and then decreased the heartbeat. On the other hand, another kind of volition, which sped up the heartbeat, initiated desynchronized activity at the precentral, central, parietal, and occipital regions, inhibited the parasympathetic system and excited the sympathetic system, and then increased the heartbeat. Moreover, information flow from posterior cortex to anterior cortex was observed during the experiment. The parietal area played an important role in triggering the sensorimotor cortex and integrating the information, and the information flow from the central and precentral cortex to heart was dominant. All that demonstrated that volition can partly control the heartbeat, but the behavior was different from the motor nervous system.


Academic Expectations of Stress Inventory: A Psychometric Evaluation of Validity and Reliability of the Persian Version.
This study aims to evaluate the psychometric properties of the Academic Expectations of Stress Inventory (AESI) in terms of validity and reliability measurements among Persian students. A total sample of 620 high-school students (nfemale = 328, nmale = 292) was recruited to complete scales on academic expectations of stress, self-efficacy, and depression. The AESI was translated from English to Persian and its translation was further checked by three experts. We used a cross-sectional research design to collect data. The results approved the internal consistency, test-retest reliability, convergent, and construct validity of the ASEI. Additionally, confirmatory factor analysis confirmed the two-factor structure of the AESI, including the expectation of self and the expectations of parents/teachers. AESI was related to depression and self-efficacy in an empirically and theoretically expected direction. Moreover, configural and metric invariance were supported by gifted vs. non-gifted groups, but not scalar. No invariance was supported by gender groups. In conclusion, the psychometric properties of the Persian version of the AESI were confirmed to be used for educational, clinical, and research purposes in Iran.


Novel insights into the disease transcriptome of human diabetic glomeruli and tubulointerstitium.
Diabetic nephropathy (DN) is the most common cause of end-stage renal disease, affecting ∼30% of the rapidly growing diabetic population, and strongly associated with cardiovascular risk. Despite this, the molecular mechanisms of disease remain unknown. RNA sequencing (RNAseq) was performed on paired, micro-dissected glomerular and tubulointerstitial tissue from patients diagnosed with DN [n = 19, 15 males, median (range) age: 61 (30-85) years, chronic kidney disease stages 1-4] and living kidney donors [n = 20, 12 males, median (range) age: 56 (30-70) years]. Principal component analysis showed a clear separation between glomeruli and tubulointerstitium transcriptomes. Differential expression analysis identified 1550 and 4530 differentially expressed genes, respectively (adjusted P < 0.01). Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses highlighted activation of inflammation and extracellular matrix (ECM) organization pathways in glomeruli, and immune and apoptosis pathways in tubulointerstitium of DN patients. Specific gene modules were associated with renal function in weighted gene co-expression network analysis. Increased messengerRNA (mRNA) expression of renal damage markers lipocalin 2 (LCN) and hepatitis A virus cellular receptor1 (HAVCR1) in the tubulointerstitial fraction was observed alongside higher urinary concentrations of the corresponding proteins neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) in DN patients. Here we present the first RNAseq experiment performed on paired glomerular and tubulointerstitial samples from DN patients. We show that prominent disease-specific changes occur in both compartments, including relevant cellular processes such as reorganization of ECM and inflammation (glomeruli) as well as apoptosis (tubulointerstitium). The results emphasize the potential of utilizing high-throughput transcriptomics to decipher disease pathways and treatment targets in this high-risk patient population.


High-performance waveguide-coupled lateral Ge/Si avalanche photodetector.
A high-performance waveguide-coupled lateral avalanche photodetector (APD) is experimentally demonstrated without silicon epitaxy and charge layer ion implantation. At the wavelength of 1550 nm, it shows a high responsivity of 48 A/W and a gain-bandwidth product (GBP) of 360 GHz. Wide-open eye diagrams at 25 Gbps can be observed at various avalanche gains. These outstanding performances indicate the proposed APD has great potential in high-speed optical transceivers for optical links.


Meta-analysis shows both congruence and complementarity of DNA and eDNA metabarcoding to traditional methods for biological community assessment.
DNA metabarcoding is increasingly used for the assessment of aquatic communities, and numerous studies have investigated the consistency of this technique with traditional morpho-taxonomic approaches. These individual studies have used DNA metabarcoding to assess diversity and community structure of aquatic organisms both in marine and freshwater systems globally over the last decade. However, a systematic analysis of the comparability and effectiveness of DNA-based community assessment across all of these studies has hitherto been lacking. Here, we performed the first meta-analysis of available studies comparing traditional methods and DNA metabarcoding to measure and assess biological diversity of key aquatic groups, including plankton, microphytobentos, macroinvertebrates, and fish. Across 215 data sets, we found that DNA metabarcoding provides richness estimates that are globally consistent to those obtained using traditional methods, both at local and regional scale. DNA metabarcoding also generates species inventories that are highly congruent with traditional methods for fish. Contrastingly, species inventories of plankton, microphytobenthos and macroinvertebrates obtained by DNA metabarcoding showed pronounced differences to traditional methods, missing some taxa but at the same time detecting otherwise overseen diversity. The method is generally sufficiently advanced to study the composition of fish communities and replace more invasive traditional methods. For smaller organisms, like macroinvertebrates, plankton and microphytobenthos, DNA metabarcoding may continue to give complementary rather than identical estimates compared to traditional approaches. Systematic and comparable data collection will increase the understanding of different aspects of this complementarity, and increase the effectiveness of the method and adequate interpretation of the results.


Understanding the canine intestinal microbiota and its modification by pro-, pre- and synbiotics - what is the evidence?
Interest in the composition of the intestinal microbiota and possibilities of its therapeutic modifications has soared over the last decade and more detailed knowledge specific to the canine microbiota at different mucosal sites including the gut is available. Probiotics, prebiotics or their combination (synbiotics) are a way of modifying the intestinal microbiota and exert effects on the host immune response. Probiotics are proposed to exert their beneficial effects through various pathways, for example production of antimicrobial peptides, enhancing growth of favourable endogenous microorganisms, competition for epithelial colonisation sites and immune-modulatory functions. Despite widespread use of pro-, pre- and synbiotics, scientific evidence of their beneficial effects in different conditions of the dog is scarce. Specific effects of different strains, their combination or their potential side-effects have not been evaluated sufficiently. In some instances, in vitro results have been promising, but could not be transferred consistently into in vivo situations. Specific canine gastrointestinal (GI) diseases or conditions where probiotics would be beneficial, their most appropriate dosage and application have not been assessed extensively. This review summarises the current knowledge of the intestinal microbiome composition in the dog and evaluates the evidence for probiotic use in canine GI diseases to date. It wishes to provide veterinarians with evidence-based information on when and why these products could be useful in preventing or treating canine GI conditions. It also outlines knowledge about safety and approval of commercial probiotic products, and the potential use of faecal microbial transplantation, as they are related to the topic of probiotic usage.


Complete Genome Sequence of the Yogurt Isolate Lactobacillus delbrueckii subsp. bulgaricus ACA-DC 87.
Lactobacillus delbrueckii subsp. bulgaricus is widely used in the production of yogurt and cheese. In this study, we present the complete genome sequence of L. delbrueckii subsp. bulgaricus ACA-DC 87 isolated from traditional Greek yogurt. Whole-genome analysis may reveal desirable technological traits of the strain for dairy fermentations.


A redox-switchable catalyst with an 'unplugged' redox tag.
Two bis-(propyl-imidazolium)-napthalenediimide (NDI) salts were prepared and used as N-heterocyclic carbene (NHC) precursors for the preparation of dimetallic complexes of rhodium and iridium. Infrared spectroelectrochemical studies indicate that the metals are sensitive to changes in the electronic state of the NDI moiety. The catalytic behavior of the rhodium and iridium complexes was tested in the cycloisomerization of alkynoic acids, where the complexes showed effective redox-switching properties.


The non-effect of parathyroidectomy in the aquatic limbless newt (Apoda, Amphibia).
In the aquatic limbless newt, Typhlonectes compressicauda (Apoda, Amphibia), serum Ca levels of parathyroidectomized newts were no lower than for the control newts at 1 week after the operation. In this species, the parathyroid glands may not be functional in raising the serum Ca levels.


The Arabidopsis embryo as a quantifiable model for studying pattern formation.
Phenotypic diversity of flowering plants stems from common basic features of the plant body pattern with well-defined body axes, organs and tissue organisation. Cell division and cell specification are the two processes that underlie the formation of a body pattern. As plant cells are encased into their cellulosic walls, directional cell division through precise positioning of division plane is crucial for shaping plant morphology. Since many plant cells are pluripotent, their fate establishment is influenced by their cellular environment through cell-to-cell signaling. Recent studies show that apart from biochemical regulation, these two processes are also influenced by cell and tissue morphology and operate under mechanical control. Finding a proper model system that allows dissecting the relationship between these aspects is the key to our understanding of pattern establishment. In this review, we present the Arabidopsis embryo as a simple, yet comprehensive model of pattern formation compatible with high-throughput quantitative assays.


Associations Between White Matter Microstructures and Cognitive Functioning in 8-Year-Old Children: A Track-Weighted Imaging Study.
Quantitative tractography using diffusion-weighted magnetic resonance imaging data is widely used in characterizing white matter microstructure throughout childhood, but more studies are still needed to investigate comprehensive brain-behavior relationships between tract-specific white matter measures and multiple cognitive functions in children. In this study, we analyzed diffusion-weighted MRI data of 71 healthy 8-year-old children utilizing white matter tract-specific quantitative measures derived from diffusion-weighted MRI tractography based on a novel track-weighted imaging approach. Track density imaging, average path length map and 4 track-weighted diffusion tensor imaging measures including: mean diffusivity, fractional anisotropy, axial diffusivity, and radial diffusivity were computed for 63 white matter tracts. The track-weighted imaging measures were then correlated with a comprehensive set of neuropsychological test scores in different cognitive domains including intelligence, language, memory, academic skills, and executive functions to identify tract-specific brain-behavior relationships. Significant correlations (P < .05, false discovery rate corrected; r = 0.27-0.57) were found in multiple white matter tracts, with a total of 40 correlations identified between various track-weighted imaging measures including average path length map, track-weighted imaging-fractional anisotropy, and neuropsychological test scores and subscales. Specifically, track-weighted imaging measures indicative of better white matter connectivity and/or microstructural development significantly correlated with higher IQ and better language abilities. Our findings demonstrate the ability of track-weighted imaging measures in establishing associations between white matter and cognitive functioning in healthy children and can serve as a reference for normal brain/cognition relationships in young school-age children and further aid in identifying imaging biomarkers predictive of adverse neurodevelopmental outcomes.


Copper-Catalyzed Defluorinative Borylation and Silylation of gem-Difluoroallyl Groups.
Stereodefined (Z)-fluoroalkenes are bioisosteres of amides and synthetic precursors to value-added fluorinated compounds, but their stereoselective synthesis remains challenging. Herein, we report a copper-catalyzed formal SN2' defluorinative borylation of 3-substituted 3,3-difluoropropenes to form 3-fluoroallylboronic esters in high yields with excellent Z/E ratios. The primary 3-fluoroallylboronic esters undergo several synthetic sequences involving SE2' substitutions, SN2' substitutions, and sigmatropic rearrangements to provide tertiary allylic fluorides.


Mechanical strain stabilizes reconstituted collagen fibrils against enzymatic degradation by mammalian collagenase matrix metalloproteinase 8 (MMP-8).
Collagen, a triple-helical, self-organizing protein, is the predominant structural protein in mammals. It is found in bone, ligament, tendon, cartilage, intervertebral disc, skin, blood vessel, and cornea. We have recently postulated that fibrillar collagens (and their complementary enzymes) comprise the basis of a smart structural system which appears to support the retention of molecules in fibrils which are under tensile mechanical strain. The theory suggests that the mechanisms which drive the preferential accumulation of collagen in loaded tissue operate at the molecular level and are not solely cell-driven. The concept reduces control of matrix morphology to an interaction between molecules and the most relevant, physical, and persistent signal: mechanical strain. The investigation was carried out in an environmentally-controlled microbioreactor in which reconstituted type I collagen micronetworks were gently strained between micropipettes. The strained micronetworks were exposed to active matrix metalloproteinase 8 (MMP-8) and relative degradation rates for loaded and unloaded fibrils were tracked simultaneously using label-free differential interference contrast (DIC) imaging. It was found that applied tensile mechanical strain significantly increased degradation time of loaded fibrils compared to unloaded, paired controls. In many cases, strained fibrils were detectable long after unstrained fibrils were degraded. In this investigation we demonstrate for the first time that applied mechanical strain preferentially preserves collagen fibrils in the presence of a physiologically-important mammalian enzyme: MMP-8. These results have the potential to contribute to our understanding of many collagen matrix phenomena including development, adaptation, remodeling and disease. Additionally, tissue engineering could benefit from the ability to sculpt desired structures from physiologically compatible and mutable collagen.


[Report of a case which survived rupture in a hepatic artery mycotic aneurysm after aortic valve replacement].
A case in which rupture of a hepatic artery aneurysm occurred 4 months after aortic valve replacement because of aortic regurgitation due to infective endocarditis (IE) is reported. The patient was a 41-year-old male who underwent aortic valve replacement and closure of an abscess cavity of the Valsalva's sinus because of aortic regurgitation and an abscess of the Valsalva's sinus complicated with active IE. His postoperative course was good with no fever. Four months postoperatively, rupture of an aneurysm of the left intrahepatic artery occurred suddenly, and the patient's life was saved by resection of the lateral segment of the left lobe of the liver. Histologically, the wall structure of the aneurysm was not preserved, infiltration of neutrophils was seen in part of the wall, and a mycotic aneurysm of the left hepatic artery within the liver cause by IE was diagnosed. In Japan, only four cases, including the present one, of mycotic aneurysm of the hepatic artery have been reported in the literature examined, and this was the first case in which the patient's life as saved after a rupture. It is essential when observing the course of IE patients to bear in mind at all times that such a complication might occur.


Cleidocranial dysplasia with hearing loss.
Cleidocranial dysplasia is an inherited skeletal anomaly that affects primarily the skull, clavicle, and dentition, which can occur spontaneously, but most are inherited in autosomal dominant mode. The skull findings are brachycephaly, delayed or failed closure of the fontanelles, presence of open skull sutures and multiple wormian bones with pronounced frontal bossing. The syndrome is notable for aplasia or hypoplasia of the clavicles. The neck appears long and narrow and the shoulders markedly droop. Oral manifestations exhibit a hypoplastic maxilla with high-arched palate. Crowding of teeth is produced by retention of deciduous teeth, delayed eruption of permanent teeth, and the presence of a large number of unerupted supernumerary teeth. We report a case of CCD in a 12-year-old girl who presented with an unaesthetic facial appearance, unerupted permanent dentition with hearing loss.


High accuracy ab initio studies of electron-densities for the ground state of Be-like atomic systems.
Benchmark results for electron densities in the ground states of Li(-), Be, C(2+), Ne(6+), and Ar(14+) have been generated from very accurate variational wave functions represented in terms of extensive basis sets of exponentially correlated Gaussian functions. For Ne(6+), and Ar(14+), the upper bounds to the energies improve over previous results known from the literature. For the remaining systems our bounds are from 0.1 to 1.1 μhartree higher than the most accurate ones. We present in graphical and, partially, numerical form results both for the radial electron densities and for the difference radial density distributions (DRD) (defined with respect to the Hartree-Fock radial density) that highlight the impact of correlation effects on electron densities. Next, we have employed these DRD distributions in studies of the performance of several broadly used orbital-based quantum-chemical methods in accounting for correlation effects on the density. Our computed benchmark densities for Be have been also applied for testing the possibility of using the mathematically strict result concerning exact atomic electron densities, obtained by Ahlrichs et al. [Phys. Rev. A 23, 2106 (1981)], for the determination of the reliability range of computed densities in the long-range asymptotic region. The results obtained for Be are encouraging.


Combined Effects of Family History of Cardiovascular Disease and Serum C-reactive Protein Level on the Risk of Stroke: A 9.2-year Prospective Study among Mongolians in China.
We aimed to evaluate the combined effect of a family history of cardiovascular disease (CVD) and high serum C-reactive protein (CRP) on the stroke incidence in an Inner Mongolian population in China. A prospective cohort study was conducted from June 2002 to July 2012, with 2,544 participants aged 20 years and over from Inner Mongolia, China. We categorized participants into four groups based on the family history of CVD and CRP levels. We adjusted for age; sex; smoking; drinking; hypertension; body mass index; waist circumference; and blood glucose, triglycerides, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol levels. Compared with the group with no family history of CVD/low CRP levels, the group with family history of CVD/high CRP levels had a hazard ratio (HR) of 1.78 [95% confidence interval (CI), 1.03-3.07; P = 0.039] of stroke, and an HR of 2.14 (95% CI, 1.09-4.20; P = 0.027) of ischemic stroke. The HRs of hemorrhagic stroke for the other three groups were not statistically significant (all P > 0.05). Participants with both a family history of CVD and high CRP levels had the highest stroke incidence, suggesting that high CRP levels may increase stroke risk, especially of ischemic stroke, among individuals with a family history of CVD.


Antirheumatic gold compounds and penicillamine enhance protein kinase C-mediated activation of the arachidonate-mobilizing phospholipase A2 in mouse macrophages.
The effects of antirheumatic gold compounds and D-penicillamine on protein kinase C- and Ca(2+)-mediated activation of arachidonate mobilization and the formation of eicosanoids in mouse macrophages have been investigated. Auranofin (0.2-2 microM) enhanced the response to phorbol ester two- to three-fold, and similar enhancement was caused by aurothiomalate, aurothioglucose, and penicillamine, but only after pretreatment for 1-4 h. The enhanced mobilization of arachidonate was accompanied by increased formation and release of prostaglandin E2 and 6-keto prostaglandin F1 alpha, but not of lipoxygenase metabolites. No such enhancement occurred when the arachidonate-mobilizing phospholipase A2 was activated directly (calcium ionophore A23187). Instead, auranofin caused selective inhibition of calcium ionophore-induced formation of leukotriene C4. Treatment of macrophages with 4 beta-phorbol 12-myristate 13-acetate causes a rapid increase in the phosphorylation and a 1.4-1.8-fold increase in the activity of the 85-kd arachidonate-mobilizing phospholipase A2 as determined in an in vitro assay. The increase in activity was further enhanced by both the gold compounds and penicillamine. These findings indicate that the target for the enhancing effect of the antirheumatic drugs is located between protein kinase C and phospholipase A2 in the signal chain leading to activation of the latter enzyme.


Primary Dermal Melanoma: A Rare Clinicopathological Variant Mimicking Metastatic Melanoma.
Primary dermal melanoma (PDM) is a rare distinct variant of cutaneous melanoma, predominantly occurring on the extremities of young or middle-aged adults. In comparison to conventional melanoma, PDM is characterized by unexpectedly prolonged survival and long-term survival. Thus, correct identification of this variant is crucial to avoid potential misdiagnosis and establish correct treatment and follow-up. In addition, no consensus and specific guidelines exist on the management of this peculiar subtype of cutaneous melanoma.


Two-stage Kondo effect in a quantum dot at a high magnetic field.
We report a strong Kondo effect (Kondo temperature approximately 4 K) at high magnetic field in a selective area growth semiconductor quantum dot. The Kondo effect is ascribed to a singlet-triplet transition in the ground state of the dot. At the transition, the low-temperature conductance approaches the unitary limit. Away from the transition, for low bias voltages and temperatures, the conductance is sharply reduced. The observed behavior is compared to predictions for a two-stage Kondo effect in quantum dots coupled to single-channel leads.


Pentacam sensitivity and specificity in detecting occludable angles.
To assess the sensitivity and specificity of Pentacam measurements in detection of occludable angles and to provide cutoff values. Observational, single-center, cross-sectional study on 64 Caucasian eyes: 28 (43.7%) primary narrow angles or primary angle-closure glaucoma, and 36 (56.2%) controls: all subjects were evaluated and classified by gonioscopy (Shaffer classification). The following measurements have been considered: superior and inferior anterior chamber angle (ACA), temporal and nasal ACA, anterior chamber depth (ACD) using 5 value representation (central, superior, inferior, nasal, temporal), and anterior chamber volume (ACV). Validity of Pentacam parameters to detect patients in Shaffer 0 or I class was assessed by receiver operating characteristic (ROC) curves analysis; cutoffs were chosen as to maximize sensitivity and specificity. All the considered Pentacam measures were statistically different between the 2 groups (p<0.0001). All Shaffer grade groups differed in all parameters (p<0.001), except for grade 0 and I, which did not differ in any. Area under the curve ROC analysis revealed high discriminant power of all Pentacam measures: ACA = 0.94; ACD = 0.91; ACD central = 0.89; and ACV = 0.89. Chosen cutoff values (ACA = 22.4°; ACD = 1.12 mm; ACD central = 1.93 mm; ACV = 84 mm3) allowed correct classification of narrow angles. The study pointed out a high power of Pentacam AVA, ACV, and ACD in detecting occludable angles. Pentacam is simple to use, reliable, and noncontact, provides parameters in a short period, and represents a possible screening tool.


Inflation and health care costs in metropolitan areas.
This paper reports on an examination of the relationship between increases in health care costs in 23 Standard Metropolitan Statistical areas and various other changes in these communities over the period 1969-1977. The other changes examined consisted of 145 variables divided into 7 categories. The categories were termed demographic, economic, community illness, prices of other goods and services, hospital, physician, and technology factors. The results show that there was little relationship between rates of medical and hospital inflation and the examined variables. Total hospital costs could be related to several of the factors, the most important of which were demographic, economic, and hospital factors.


Effect of invasive strategy on different genders of Chinese patients with non-ST-elevation myocardial infarction.
The aim of this study was to determine the impact of in-hospital revascularization on different genders and to compare the gender difference in short- and long-term prognosis of Chinese patients with non-ST-elevation myocardial infarction (NSTEMI). The benefit of invasive strategy between the genders of Asian ethnic populations with NSTEMI remains unclear. A total of 343 consecutive NSTEMI patients were enrolled, 104 (30%) of them were women. All patients were followed up for at least 3 years or until the occurrence of a major event. The primary end point was all-cause death. The secondary end point was the combined occurrence of death or myocardial (re-)infarction (MI). The adjusted in-hospital and long-term clinical outcomes were similar between men and women. However, in-hospital revascularization significantly reduced long-term mortality and composite endpoint in men (P < 0.001), but not in women. After risk stratification by GRACE score, there was favorable effect of invasive strategy in high-risk women. In a multivariate Cox regression analysis, GRACE score (hazard ratio; HR, 1.017; P < 0.001) and in-hospital revascularization (HR, 0.516; P = 0.008) were the independent predictors of death or MI in men. However, only GRACE score was the independent predictor of composite endpoint in women (HR, 1.012; P = 0.004). In Asian ethnic patients with NSTEMI, the in-hospital and long-term prognosis were similar between men and women. In-hospital revascularization has a benefit in men and high-risk women for reducing the all-cause death at 1 and 3 years. Our data provide evidence supporting the guideline recommendation for an invasive strategy in high-risk women.


Three-dimensional reconstruction from serial sections. V. Calibration of dimensional changes incurred during tissue preparation and data processing.
Three-dimensional (3-D) reconstructions from serial tissue sections produce a table of x, y, z coordinates (i.e., a numerical description of the object) that will support 3-D computer graphics displays and morphometric analyses. While measures such as volume or surface area can be generated interactively, almost instantaneously, they are usually of unknown accuracy due to artifacts that may be introduced at two different stages: (1) tissue shrinkage during dehydration and polymerization of a plastic and compression or expansion during sectioning and mounting and (2) geometric and intensity distortions during image capture and data processing. This paper describes simple methods for (1) introducing fiducials (reference marks) that allow measurement of the net distortion incurred during tissue preparation and (2) estimating the amount of geometric distortion arising during image capture and data processing. Application of these methods showed that the net areal change introduced in dog and sheep hearts during tissue processing amounted to +/- 5%. Apparently, the substantial shrinkage that occurs during tissue processing is largely compensated for by the expansion during tissue sectioning and mounting. The methods described may have application to other semisolid tissues.


Comparison of Rectus Femoris Transfer Surgery Done Concomitant With Hamstring Lengthening or Delayed in Patients With Cerebral Palsy.
Children with spastic cerebral palsy frequently develop stiff knee gait. A common treatment of flexed knee gait is lengthening of the hamstring tendons. It has been shown that minimum knee extension improves after hamstring surgeries. However, it has been observed that a decreased peak knee flexion in swing may be a complication of hamstring lengthening (HSL). This has been noted to occur because of an overactive rectus femoris during the swing phase of gait. A common treatment of decreased knee flexion in swing is distal rectus femoris transfer (DRFT). The purpose of this study is to compare the differences between doing DRFT concomitantly with HSL and doing delayed DRFT after HSL. A total of 111 children with cerebral palsy (74 males and 37 females) who underwent HSL were reviewed retrospectively. All patients who met the inclusion criteria were divided into 3 groups, 28 subjects in the HSL alone group (H), 57 subjects in the HSL with concomitant rectus femoris transfer group (C), and 26 subjects in the HSL with delayed rectus femoris transfer group (D). The groups had similar minimum knee flexion in stance preoperatively and postoperatively. Group D's minimum knee flexion in stance improved to 5.5±12.7 degrees after HSL, but increased to 8.8±11.6 degrees after DRFT. Groups D and H had statistically significant reduction in maximum knee flexion in swing after HSL (P<0.05). Maximum knee flexion in swing was statistically significantly reduced in the D group after DRFT (P<0.05), but the C group was not statistically different from preoperative after DRFT (P>0.05). The C and D groups had similar total knee excursion postoperatively. The H group had less knee excursion than the other 2 groups, but it was not significant. The group that had DRFT concomitantly with HSL maintained maximum knee flexion in swing phase postoperatively. Although the group that had delayed DRFT had a reduction in maximum knee flexion after isolated HSL, gains in swing phase motion were achieved after delayed DRFT (comparable to that of the simultaneous group). Level II.


Allocating treatment options to patient profiles: clinical art or science?
For many researchers, the disappointing results of Project MATCH were the death blow for any further activities in the field of patient-treatment interactions. On the other hand, we have an increased knowledge of patient heterogeneity and a greater variety of treatment options than before, and allocation guidelines for an ongoing process of patient-placement decisions are of high practical relevance. To analyse deficits in the current research and to provide suggestions for future action. It is argued that (1) certain major design aspects of Project MATCH and other research studies--such as stringent patient exclusion criteria and low treatment 'dosage'-minimize the chances of detecting possible patient-treatment interactions and (2) Project MATCH obscures our view of previous treatment-allocation research findings. Several research strategies and specific research topics are suggested for (1) improving the theoretical and methodological basis for detecting possible patient-treatment interactions and (2) stimulating research on major treatment decision needs, such as site, setting, time in treatment (extensiveness and intensity), service components and specific treatment modules. More international research cooperation is needed to clarify the inconsistent findings.


Effects of exposure to low pH on the lateral mobility of influenza hemagglutinin expressed at the cell surface: correlation between mobility inhibition and inactivation.
To investigate the possible role of viral glycoprotein mobility in membrane fusion, fluorescence photobleaching recovery was employed to study the effects of exposure to mildly acidic pH (required to convert many viral fusion proteins to the fusion-active form) on the lateral mobility of influenza hemagglutinin (HA) proteins expressed at the surface of transfected cells. HA proteins from two different strains were compared: X:31 HA, which is activated by a brief exposure to pH 4.9 but is irreversibly inactivated at longer exposure times, and HA from A/Japan/305/57, which is relatively stable to inactivation at this pH [Puri, A., Booy, F.P., Doms, R.W., White, J.M., & Blumenthal, R. (1990) J. Virol. 64, 3824-3832]. The HA proteins from both strains, expressed in CV-1 cells using VS-40 vectors, exhibited relatively unrestricted lateral diffusion at the cell surface. The high mobility persisted following a brief exposure (1 min) to pH 4.9 to mediate conversion to the fusogenic state. Longer times (up to 15 min) of preincubation at pH 4.9 inhibited the lateral mobility of X:31 HA (the lateral diffusion rate was markedly reduced, followed by immobilization) but not of A/Japan HA, whose fusion activity is resistant to such treatment. Inhibition of the lateral mobility of X:31 HA due to preincubation at low pH was not specific to the CV-1 cells and was found also in a CHO cell line stably expressing this protein. The results presented demonstrate a close correlation between loss of mobility and inactivation of fusogenic activity, in accord with the notion that lateral motion of the HA proteins is required for fusion.(ABSTRACT TRUNCATED AT 250 WORDS)


Production of a truncated soluble human semicarbazide-sensitive amine oxidase mediated by a GST-fusion protein secreted from HEK293 cells.
Elevated levels of semicarbazide-sensitive amine oxidase (SSAO) activity have been observed in several human conditions such as congestive heart failure, diabetes mellitus, and inflammation. The reactive aldehydes and hydrogen peroxide produced by SSAO have been suggested to contribute to the progression of vascular complications associated with these conditions. In addition, SSAO activity has been shown to be involved in the leukocyte extravasation process at sites of inflammation. To facilitate characterization and development of specific and selective inhibitors of SSAO, we have developed a method for production of recombinant human SSAO. The extracellular region (residues 29-763) of human SSAO was expressed in HEK293 cells in fusion with a mutated Schistosoma japonicum glutathione S-transferase (GST) and secreted to the culture medium. The mutGST-SSAO fusion protein was purified in a single step by glutathione-affinity chromatography followed by site-specific cleavage using a GST-3C protease fusion protein to remove the mutGST fusion partner. A second glutathione-affinity chromatography step was then used to capture both the mutGST fusion partner and the GST-3C protease, resulting in milligram quantities of pure, enzymatically active, and soluble recombinant human SSAO.


Structures, dynamics, and water permeation free energy across bilayers of Lipid A and its analog studied with molecular dynamics simulation.
Fundamental studies of the supramolecular layer structures, dynamics and water permeation free energy of hexa-acyl-chain Lipid A and its analogue of tetra-acyl chains would be useful for polymer membranes design for endotoxin removal in water treatment, drug delivery and other biotechnologies. In this work, we studied their supramolecular bilayer by using molecular dynamics simulations and efficient free energy computations. Our simulation accuracy was verified by the agreement between the bilayer structural properties (structure factor, bilayer thickness, and the area per lipid) and lateral diffusion coefficient in our simulation and experimental measurements. More importantly, our simulation for the first time illustrated hexagonal compact packing of the hydrocarbon acyl chains within a leaflet of Lipid A membrane (at 298 K and water content of 40 wt %), which is consistent with experiments. In contrast, Lipid A analogue is found with less ordered ripple structures at the same condition. Our study also demonstrated slower dynamics and larger and broader free energy barrier (∼23 kJ/mol) for water permeation for Lipid A, compared with that of Lipid A analogue. Moreover, the analysis of dynamics showed that highly hydrated hydrophilic diglucosamine backbone is structurally stable, whereas the interdigitated hydrophobic acyl chain tails inside the membrane with faster dynamics screen the aqueous environment from the lipid interior and also reinforce the membrane's structural stability.


Prolonged survival of a patient with left ventricular pseudoaneurysm following myocardial infarction and mitral valve replacement.
We present the case of a patient with left ventricular pseudoaneurysm following acute myocardial infarction. Survival for 2 years following diagnosis, despite the large size of the aneurysm, and subsequent management with cardiac transplantation represent unusual and interesting aspects of this complication of myocardial infarction.


Cationic Surfactant-Based Electrolyte Additives for Uniform Lithium Deposition via Lithiophobic Repulsion Mechanisms.
Lithium metal is among the most promising anode materials for high-energy batteries due to its high theoretical capacity and lowest electrochemical potential. However, dendrite formation is a major challenge, which can result in fire and explosion of the batteries. Herein, we report on hexadecyl trimethylammonium chloride (CTAC) as an electrolyte additive that can suppress the growth of lithium dendrites by lithiophobic repulsion mechanisms. During the lithium plating process, cationic surfactant molecules can aggregate around protuberances via electrostatic attraction, forming a nonpolar lithiophobic protective outer layer, which drives the deposition of lithium ions to adjacent regions to produce dendrite-free uniform Li deposits. Thus, an excellent cycle of 300 h at 1.0 mA cm-2 and rate performance up to 4 mA cm-2 are available safely in symmetric Li|Li cells. In particular, significantly enhanced cycle and rate performance were achieved when the electrolyte with CTAC additives was used in lithium-sulfur and Li|LiNi0.5Co0.2Mn0.3O2 full cells. The effects of carbon chains, anions of surfactant, and electrostatic repulsion on the deposition of lithium anodes are reported. This work advances research in inhibiting Li dendrite growth with a new electrolyte additive based on cationic surfactants.


Fatty acid transporter expression and regulation is impaired in placental macrovascular endothelial cells in obese women.
Fetal fatty acid (FA) delivery is ultimately controlled by placental transport. Focus has been the maternal-placental interface, but regulation at the feto-placental interface is unknown. Placental macrovascular endothelial cells (EC) (n = 4/group) and trophoblasts (TB) (n = 5/group) were isolated from lean (pregravid BMI <25 kg/m2) and obese (body mass index (BMI) > 30) women. Fatty acid transporters FAT/CD36, FABPpm, FATP4, FABP 3, 4 and 5, PLIN2 and PPARα, δ, γ expression, was measured in EC and TB. Transporter response to 24 h palmitate (PA) was assessed. mRNA expression of FABP3, 4, 5 and PPARγ was 2- to 3-fold reduced in EC of obese versus lean women (p < .03), but not in TB. Protein level of FABPpm was 20% lower in obese (p < .05). Palmitate (PA) up-regulated CD36, FABP3, FABP4, and PLIN2 gene expression by 3- to 4-fold in lean but not obese EC (p < .05), while PA increased FABP4 and PLIN2 in lean and obese TB, and FABP5 in lean (p < .05) EC. PA exposure up-regulated peroxisome proliferator activated receptors (PPARs) 2-fold in lean and obese EC (p < .05), but not in TB. In obese women, FA transporter expression is lower in placental EC, but not TB, and less sensitive to saturated FA, compared to lean women. FA transport may be regulated at the feto-placental interface.


Management of Citrus Canker in Argentina, a Success Story.
Citrus canker is an important bacterial disease of citrus in several regions of the world. Strains of Xanthomonas citri type-A (Xc-A) group are the primary pathogen where citrus canker occurs. After Xc-A entered the Northeast of Argentina in 1974, the disease spread rapidly from 1977 to 1980 and then slowed down and remained moving at slow pace until 1990 when it became endemic. Citrus canker was detected in Northwest Argentina in 2002. This paper presents the main steps in the fight of the disease and the management strategies that have been used to control citrus canker at this time. We think the process might be usefull to other countries with the same situation. Results from more than 40 years of research in Northeast (NE) Argentina indicate that we are at the limit of favorable environment for the disease. The severity of citrus canker is greatly affected by the environment and El Niño Southern Oscillation (ENSO) phenomenon which causes cyclic fluctuations on the disease intensity in the NE region. Weather-based logistic regression models adjusted to quantify disease levels in field conditions showed that the environmental effect was strongly modulated by the distance from a windbreak. Production of healthy fruits in citrus canker endemic areas is possible knowing the dynamics of the disease. A voluntary Integrated Plan to Reduce the Risk of Canker has been in place since 1994 and it allows growers to export unsymptomatic, uninfested fresh fruit to countries which are free of the disease and require healthy, pathogen free fruits. The experience from Argentina can be replicated in other countries after appropriate trials.


Physiological assessment of head-out aquatic exercises in healthy subjects: a qualitative review.
In the last decades head-out aquatic exercises became one of the most important physical activities within the health system. Massive research has been produced throughout these decades in order to better understand the role of head-out aquatic exercises in populations' health. Such studies aimed to obtain comprehensive knowledge about the acute and chronic response of subjects performing head-out aquatic exercises. For that, it is assumed that chronic adaptations represent the accumulation of acute responses during each aquatic session. The purpose of this study was to describe the "state of the art "about physiological assessment of head-out aquatic exercises based on acute and chronic adaptations in healthy subjects based on a qualitative review. The main findings about acute response of head-out aquatic exercise according to water temperature, water depth, type of exercise, additional equipment used, body segments exercising and music cadence will be described. In what concerns chronic adaptations, the main results related to cardiovascular and metabolic adaptations, muscular strength, flexibility and body composition improvements will be reported. Key pointsSeveral papers reported consistent and significant improvement in physical fitness (e.g., aerobic capacity, muscular strength, flexibility and body composition) after a program of head-out aquatic exercise with at least eight weeks.Chronic adaptations to head-out aquatic exercise programs are the cumulative result of appropriate acute responses during the exercise session.Appropriate acute adaptations can be obtained taking into account the water temperature, water depth, type of exercise and its variants, the equipment used and the segmental cadence according to the subjects' profile.


Family satisfaction with care provided by nurse practitioners to nursing home residents with dementia at the end of life.
The purpose of this study was to examine family satisfaction with care provided by nurse practitioners (NP) to nursing home (NH) residents with dementia. A survey was mailed to 239 family members of nursing home residents who died with dementia. One open-ended question was added to provide comment about the care provided by the NP. A total of 131 surveys were returned (response rate 55%). The study revealed that 98% of family members agreed that they were satisfied with the end-of-life care provided by the NP. Survey responses were used to analyze the associations of communication, comfort, and satisfaction with NPs to total satisfaction with end-of-life care. Pearson's correlations demonstrated that overall satisfaction was significantly associated with NP-family communication, resident comfort, and satisfaction with NP care. Findings suggested that NPs using a model of care that emphasizes advance care planning, communication, and comfort results in high satisfaction of family members.


Scaling up the predator functional response in heterogeneous environment: when Holling type III can emerge?
Accurate parametrization of functional terms in model equations is of great importance for reproducing the dynamics of real food webs. Constructing models over large spatial and temporal scales using mathematical expressions obtained based on microcosm experiments can be erroneous. Here, using a generic spatial predator-prey model, we show that scaling up the microscale functional response of a predator can result in qualitative alterations of functional response on macroscales. In particular, a global functional response of sigmoid type (Holling type III) can emerge as a result of non-linear averaging of non-sigmoid local responses (Holling type I or II). We demonstrate that alteration between the local and the global response in the model is a result of the interplay between density-dependent dispersal of the predator across the habitat and heterogeneity of the environment. Using the method of aggregation of variables, we analytically derive the mathematical formulation of the global functional response as a function of the total amount of prey in the system, and reveal the key parameters which control the emergence of a Holling type III global response. We argue that this mechanism by which a global Holling type III emerges from a local Holling type II response has not been reported in the literature yet: in particular, Holling type III can emerge in the case of a fixed gradient of resource distribution across the habitat, which would be impossible in priorly suggested mechanisms. As a case study, we consider the interaction between phytoplankton and zooplankton grazers in the water column; and we show that the emergence of a Holling type III global response can allow for the efficient top-down regulation of primary producers and stabilization of planktonic ecosystems under eutrophic conditions.


Dysrhythmias and blood pressure changes associated with thrombolysis.
Recent technologic advances facilitate salvage of viable myocardium before the process of myocardial infarction is complete. The aim of thrombolytic agents is to restore antegrade flow of blood in occluded coronary arteries. The process of reperfusion may be dysrhythmogenic because of the heterogeneous return of electrical activity in myocardial cells. This study examined the incidence and type of dysrhythmia occurrence and the associated changes in mean arterial blood pressure (MAP) during infusion of tissue-type plasminogen activator (TPA). A retrospective chart review of 41 subjects showed that 80% of subjects experienced dysrhythmias during TPA therapy. The most common dysrhythmia was sinus bradycardia, followed by idioventricular/accelerated idioventricular rhythm, ventricular premature beats, and ventricular tachycardia/fibrillation. There was a significant difference between MAP changes when there were no dysrhythmias and MAP changes when dysrhythmias occurred (p less than 0.05). The largest change in MAP (-22.71 mm Hg) was observed when dysrhythmias occurred in those subjects with blockage of the left anterior descending artery, although there was no statistically significant difference in changes in MAP among the groups of different sites of blockage (p greater than 0.05).


Haemorrhagic encephalitis in the garb of scrub typhus.
A 19-year-old girl presented with fever, headache, vomiting and drowsiness. She had grade 1 papilloedema and neck rigidity but no focal deficits or seizures. Cerebrospinal fluid analysis revealed lymphocytic pleocytosis, slightly elevated protein and normal glucose. MRI of the brain showed a hyperintense lesion in left ganglio-capsular region on the fluid attenuation inversion recovery sequence with perilesional oedema and mild midline shift. Haemorrhage was seen in the region on susceptibility weighted imaging . The patient was thoroughly investigated for known causes of meningoencephalitis, but the diagnosis of scrub typhus was delayed till the 10th day of illness. She was treated with doxycycline for 2 weeks and had marked improvement, both clinically and radiologically. Literature review has revealed that although meningoencephalitis in scrub typhus is not uncommon, such atypical lesions on brain MRI are a rarity. Serial imaging was performed to document the disease progression and resolution on treatment.


Predicting what can go wrong at endoscopic ultrasound: a large series experience.
Although prior studies have evaluated complications following endoscopic ultrasound (EUS), data on the incidence of unplanned events at EUS, defined as any deviation from the preprocedure plan, are lacking. The aim of this study was to define the incidence, nature, clinical predictors and implications of unplanned events at EUS. Case control study. Tertiary referral centre. 4624 consecutive patients undergoing EUS during a 6 year period were enrolled. For each patient with an unplanned event, two patients with a successful EUS in the same calendar year were randomly selected as controls. Unplanned events occurring prior to, during or after EUS procedures were prospectively recorded in a database. 192/4624 patients had an unplanned event (4.1%). In all, 2.1% had a failed procedure for anatomical reasons, 1.3% because of restlessness despite standard sedation and 0.5% for technical reasons. Adverse events occurred in 0.2%. There was no mortality but 4/6 patients with adverse events had to be admitted to hospital (2/4 operated). Eighty-two per cent of patients with an unplanned event had incomplete examinations, 14% had no procedure performed and 4% had complete procedures. In a multivariate analysis, only Afro-Caribbean patient origin, inpatient procedure and cancer staging procedure were independently related to unplanned events (p<0.05 for all). Unplanned events at EUS are mainly due to anatomical reasons and restlessness, despite sedation. They commonly result in incomplete examination and are related to Afro-Caribbean origin, inpatient procedure and cancer staging.


Procedural Outcomes in Patients Treated with Percutaneous Coronary Interventions within Chronic Total Occlusions Stratified by Gender.
It has been demonstrated that gender differences are related to different procedural and long-term clinical outcomes among a general patient population treated using percutaneous coronary interventions (PCI). The objective of our analysis was to conduct assessment regarding the relationship between gender and procedural outcomes in patients treated for PCI regarding chronic total occlusions (CTO), based on a large, real-life registry. Data used to conduct the following analysis was derived from the national registry of percutaneous coronary interventions (ORPKI), upheld in co-operation with the Association of Cardiovascular Interventions (AISN) of the Polish Cardiac Society. The study involved data procured from the registry within the period from January 2014 to December 2020. All subsequent CTO procedures recorded in the registry during that period were included in the analysis. We assessed the correlation between gender and the overall rate of periprocedural complications, procedure-related mortality, and success evaluated as TIMI flow grade 3 after the procedure by univariate and multivariable modeling. At the time of conducting our investigation, there were 162 existing and active CathLabs, at which 747,033 PCI procedures were carried out during the observational period. Of those, 14,903 (1.99%) were CTO-PCI procedures, and 3726 were women (25%). The percentage share between genders did not experience any significant changes during the consecutive years observed in the current analysis. Overall periprocedural complication rate was greater among women than men (3.45% vs. 2.31%, p = 0.02). A comparable relationship was noted for procedural mortality (0.7% vs. 0.2%, p = 0.006), while procedural success occurred more often in the case of women (69.3% vs. 65.2%, p < 0.001). Women were found to be more frequently affected by periprocedural complications (OR = 1.553; 95%CI: 1.212−1.99, p < 0.001) as well as procedural success (OR = 1.294; 95%CI: 1.151−1.454, p < 0.001), evaluated using multivariable models. Based on the current analysis performed on all-comer patients treated using PCI in CTO, women are affected by more frequent procedural complication occurrence as well as greater procedural success compared to men.


Has pharmacy adequately promoted pharmaceutical discoveries to the public?
In summary, twentieth-century British and American cards published by the organisations of pharmacy albeit a limited window into public relations--suggest that relatively little attention was given to offering the public an understanding of the science basis of pharmacy or the nature of pharmacy research. On the other hand, clear hints of this came from industry despite being diluted, some might say tainted, with overt commercialism. Thus it is suggested that the public came to associate industry with pharmacy research, a suggestion that needs to be examined in the light of other approaches to PR. It is, of course, not surprising that PR from pharmacy's professional bodies has focused largely on community practice. However, it is reasonable to ask, What is the cost in terms of professional image when opportunities to promote an understanding of the science of pharmacy are given little attention? Indeed, it seems to me that it was soon forgotten that an emphasis placed on the science base of pharmacy was very much behind the successful efforts in establishing the Pharmaceutical Society and a professional image for pharmacy. I suggest, too, that the pattern of limited science PR contributes, unconsciously, to current concerns over the place of scientists in the new professional society. As is well known, interminable debate exists over what the public sees as 'professional'. Even so, I think few would disagree that an image of science can be more than helpful. Maybe, in the current upheaval for British pharmacy, there is a case for the publication of free cards analogous to those recently produced by the School of Pharmacy, although only so long as they indicate, by way of context, both the science and humanity demanded for pharmacy practice.


CRP-Based Cardiovascular Risk Assessment: New Conventional CRP Assay Fit for Purpose?
Subclinical inflammation was shown to play a role in the context of cardiovascular disorder processes. American College of Cardiology/American Heart Association guidelines on cardiovascular risk assessment in specific clinical contexts recommend the use of C-reactive protein (CRP) measurement with high sensitive (hs)-CRP assays that meet the precision requirements for values <2 mg/L. Until now, only hs-CRP assays reached the required limit of quantification. However, new regular CRP assays allow measuring CRP down to 0.6 mg/L. A multisite comparative study between hs-CRP and a new conventional CRP assay (Tina-quant) was performed to evaluate the possibility of using regular CRP assays for cardiovascular risk assessment. A satisfactory concordance was observed between regular CRP assays and the hs-CRP assay. Both assays met the analytical precision requirements at the different cutpoints tested (1.00, 2.00, and 3.00 mg/L). These results suggest that this new regular CRP assay can be used for cardiovascular risk assessment, which is expected to provide substantial operational and financial advantages when compared with hs-CRP assays.


Modifier Effect in Silica-Supported FePO4 and Fe-Mo-O Catalysts for Propylene Glycol Oxidation.
Currently, catalytic processing of biorenewable raw materials into valuable products attracts more and more attention. In the present work, silica-supported FePO4 and Fe-Mo-O catalysts are prepared, their phase composition, and catalytic properties are studied in the process of selective oxidation of propylene glycol into valuable mono- and bicarbonyl compounds, namely, hydroxyacetone and methylglyoxal. A comparative analysis of the main routes of propylene glycol adsorption with its subsequent oxidative conversion into carbonyl products is carried out. The DFT calculations show that in the presence of adsorbed oxygen atom, the introduction of the phosphate moiety to the Fe-containing site strengthens the alcohol adsorption on the catalyst surface with the formation of the 1,2-propanedioxy (-OCH(CH3)CH2O-) intermediate at the active site. The introduction of the molybdenum moiety to the Fe-containing site in the presence of the adsorbed oxygen atom is also energetically favorable, however, the interaction energy is found by 100 kJ/mol higher compared to the case with phosphate moiety that leads to an increase in the propylene glycol conversion while maintaining high selectivity towards C3 products. The catalytic properties of the synthesized iron-containing catalysts are experimentally compared with those of Ag/SiO2 sample. The synthesized FePO4/SiO2 and Fe-Mo-O/SiO2 catalysts are not inferior to the silver-containing catalyst and provide ~70% selectivity towards C3 products, while the main part of propylene glycol is converted into methylglyoxal in contrast to the Ag/SiO2 catalyst featuring the selective transformation of only the secondary C-OH group in the substrate molecule under the studied conditions with the formation of hydroxyacetone. Thus, supported Fe-Mo-O/SiO2 catalysts are promising for the selective oxidation of polyatomic alcohols under low-temperature conditions.


[An analysis of health literacy about diabetes prevention and control and its influencing factors among the residents in six provinces in China].
To investigate the health literacy about diabetes prevention and control and its influencing factors among the public in China. A multistage stratified random sampling method was applied to investigate urban and rural residents aged 18-60 years among six provinces in China during March and May, 2013. The Questionnaire of Health Literacy of Diabetes Mellitus of the Public in China was used to conduct the survey. The influencing factors of health literacy about diabetes prevention and control were analyzed by logistic regression. The results of the survey were standardized by the 6(th) national census data. A total of 4 416 persons were interviewed. A total of 4 282 valid questionnaires including 1 986 males (46.4%) and 2 296 females (53.6%) were obtained. The efficiency rate was 97.0%. The level of health literacy about diabetes prevention and control among the public in China was 32.7% (1 036/2 399). And this rate was 40.5%, 36.5% and 15.4% in east, middle and west of China, respectively. Take the west region as reference, the health literacy about diabetes prevention and control in east China was high (OR = 2.510, 95% CI: 1.931-3.263), central China was in the second place (OR = 2.083, 95% CI: 1.579-2.749). The health literacy about diabetes prevention and control among males was lower than that in females (OR = 0.488, 95% CI: 0.402-0.593). The higher education level the respondents had, the higher the health lireracy level about diabetes prevention and control. Taking the primary school and below education level as reference, the health lireracy level about diabetes prevention and control of respondents with a secondary education was higher (OR = 1.103, 95% CI: 0.812-1.499), and that of college or above degree was the highest (OR = 2.029, 95% CI: 0.460-0.870). The health literacy about diabetes prevention and control among civil servants and institution staff was high, the enterprise personnel was in the second place (OR = 0.632, 95% CI: 0.460-0.870), the literacy level among the rural residents was very low (OR = 0.339, 95% CI: 0.234-0.491). The health literacy about diabetes prevention and control among people who have a family history of diabetes was relatively higher (OR = 1.570, 95% CI: 1.222-2.018 ). The health literacy about diabetes prevention and control among people who considered that they have diabetes risk was higher than that among people who considered they didn't (OR = 1.821, 95% CI: 1.317-2.517). The east region, females, a high educational level, civil servants and public officers, having a family history of diabetes, self-assessed risk of getting diabetes were protective factors of health literacy about diabetes prevention and control.


Impact of diffuse layer processes on contaminant forward and back diffusion in heterogeneous sandy-clayey domains.
Low-permeability aquitards can significantly affect the transport, distribution, and persistence of contaminant plumes in subsurface systems. Although such low-permeability materials are often charged, the key role of charge-induced electrostatic processes during contaminant transport has not been extensively studied. This work presents a detailed investigation exploring the coupled effects of heterogeneous distribution of physical, chemical and electrostatic properties on reactive contaminant transport in field-scale groundwater systems including spatially distributed clay zones. We performed an extensive series of numerical experiments in three distinct heterogeneous sandy-clayey domains with different levels of complexity. The flow and reactive transport simulations were performed by explicitly resolving the complex velocity fields, the small-scale electrostatic processes, the compound-specific diffusive/dispersive fluxes and the chemical processes utilizing a multi-continua based reactive transport code (MMIT-Clay). In each particular domain, numerical experiments were performed focusing on both the forward and back diffusion through the sandy-clayey interfaces. The results illuminate the control of microscopic electrostatic mechanisms on macroscopic mass transfer. Coulombic interactions in the clay's diffuse layer can significantly accelerate or retard a particular species depending on its charge. Furthermore, the chemical heterogeneity plays a major role in mass storage and release during reactive transport. Neglecting such processes can lead to substantial over- or underestimation of the overall transport behavior, which underlines the need for integrated physical, chemical and electrostatic approaches to accurately describe mass transfer processes in systems including low-permeability inclusions.


Development and validation of a questionnaire measuring knowledge, attitudes, and current practices of primary healthcare physicians regarding road injury prevention in older adults.
Older adults present high risk of involvement in road crashes. Preventive interventions conducted by their primary healthcare physicians (PHPC) could reduce this public health issue. The objective of this study was to design and validate a self-administered questionnaire that measures the knowledge, attitudes, and current practices (CP) of PHCP in Spain regarding the prevention of road injuries in older adults. One thousand eight hundred and ninety-seven PHCP completed a questionnaire piloted previously in an expert panel and two convenience samples of physicians. It comprised 78 items grouped in five sections and was mainly focused on exploring three constructs: knowledge, attitudes, and CP. Exploratory factor analysis was used to obtain evidence of internal structure validity. Reliability was assessed through Cronbach's α coefficient. Correlation coefficients for the scores constructed for each of the extracted factors were calculated to assess convergent and discriminant validity. Factor analysis extracted four factors each for the knowledge and attitudes constructs, and three factors for the CP construct, which explained more than 55% of the variance in each construct. Except for two factors of the knowledge construct regarding existing health problems associated to the risk of involvement in road crashes, the clustering pattern of all other items across the remaining nine factors was consistent and in agreement with previous knowledge. Cronbach's α values were greater than 0.7 for all constructs. Our questionnaire appears to be valid enough to assess the attitudes, CP, and medication-related knowledge of PHCP in Spain regarding the prevention of road injuries in older adults.


An anti-Parkinson drug ropinirole depletes orexin from rat hypothalamic slice culture.
Non-ergot-type dopamine receptor agonists such as ropinirole are used for the treatment of Parkinson disease, but they occasionally show serious side effects including sleep attacks and daytime sleepiness. These symptoms are reminiscent of narcolepsy, a major sleep disorder. Because narcolepsy is thought to result from deficiency of a hypothalamic neuropeptide orexin, we examined whether ropinirole affected the integrity of orexin-containing neurons, using organotypic slice culture of rat hypothalamus. Application of ropinirole induced a significant decrease in the number of orexin-immunoreactive neurons. The same treatment showed no significant effect on the number of melanin-concentrating hormone-immunoreactive neurons. The decrease of orexin-immunoreactive neurons was reversible after washout of ropinirole and was not accompanied by induction of cell death. Antagonism of dopamine D(2) receptors and of serotonin 5-HT(1A) receptors attenuated the effect of ropinirole, suggesting involvement of these receptors in depletion of orexin. On the other hand, a moderate concentration of N-methyl-d-aspartate that excited orexin neurons counteracted the effect of ropinirole on the number of orexin-immunoreactive neurons. These results suggest that ropinirole can cause deficiency of orexin by inhibiting excitatory activities of orexin neurons, which may be relevant to the adverse actions of this drug on sleep and wakefulness.


Nitrate administration increases blood flow in dysfunctional but viable myocardium, leading to improved assessment of myocardial viability: A PET study.
SPECT with 99mTc-labeled agents is better able to detect viability after nitrate administration. Nitrates induce vasodilation and may increase blood flow to severely hypoperfused but viable myocardium, thereby enhancing tracer delivery and improving the detection of viability. Quantitative data on the changes in blood flow are lacking in SPECT but can be provided by PET. The aim of the present study was to use PET to evaluate whether nitrate administration increases blood flow to chronically dysfunctional but viable myocardium. 13N-Ammonia PET was used to quantitatively assess blood flow, and 18F-FDG PET was used as the gold standard to detect viable myocardium. Twenty-five patients with chronic ischemic left ventricular dysfunction underwent 13N-ammonia PET at rest and after nitrate administration. A significant increase in nitrate-enhanced blood flow was observed in viable segments (from 0.55 +/- 0.15 to 0.68 +/- 0.24 mL/min/g, P < 0.05). No statistically significant change in blood flow was observed in nonviable segments (0.60 +/- 0.20 vs. 0.55 +/- 0.18 mL/min/g). A ratio of at least 1.1 for nitrate-enhanced flow to resting flow allowed optimal detection of viable myocardium, yielding a sensitivity of 82% with a specificity of 100%. 13N-Ammonia PET showed a significant increase in nitrate-enhanced blood flow in viable myocardium, whereas blood flow remained unchanged after nitrate administration in nonviable myocardium. Nitrate use during myocardial perfusion imaging will lead to improved assessment of myocardial viability.


Clinicopathologic Characterization of Bilateral Testicular Germ Cell Tumors With Immunohistochemical Evaluation of Mismatch Repair and BRAF (V600E) Genes Mutations.
The incidence of bilateral testicular germ cell tumor (TGCT) is 1% to 5%. Despite the high rate of treatment success, resistance to chemotherapy has a detrimental effect. Some studies found MMR and BRAF gene mutations to be associated with chemotherapy resistance, which has not been found by others. However, the role of microsatellite instability (MSI) and BRAF mutations in bilateral disease has not been investigated. In this article, we studied the clinicopathologic characteristics and immunohistochemical expressions of MMR and BRAF in 13 patients with bilateral TGCT. Bilateral tumors were found in 4% of patients in our data. The mean ages at the first and subsequent diagnoses were 26.9 and 28.3 years, respectively. Eleven patients had metachronous disease; and the mean period between both tumors was 4.9 years. Six had mixed GCTs (MGCT) initially and later developed contralateral seminoma, 3 had bilateral MGCTs; 1 initially had pure embryonal carcinoma and subsequently MGCT and finally, 1 patient had initial seminoma and contralateral germ cell neoplasia in situ only. Of the patients with synchronous GCT, 1 had a MGCT and contralateral non-seminoma and 1 had seminoma and contralateral MGCT. In metachronous cases, 40% and 78% had an initial and subsequent stage of pT1, respectively. Hormonal and/or metastatic recurrence was observed in 30% of metachronous tumors. Six patients received chemotherapy, including patients with metastasis. No progression occurred after therapy. MLH1, PMS2, MSH2, and MSH6 staining was retained in all tumors. No BRAF staining was found. In conclusion, we found no association between bilateral TGCT and the MMR/MSI pathway and that subsequent metachronous tumors behaved much more indolently.


[Pathological gambling in Israel as a medical and social problem].
This article discusses the phenomenon of pathological gambling in Israel today, emphasizing its medical as well as social dimensions. After a brief historical review of pathological gambling in world and Jewish history, certain psychological aspects of the disorder are reviewed. The typology of gamblers is mentioned, and the relationship between gambling and affective disorders is briefly discussed. Some of the forensic implications of pathological gambling are also mentioned.


Pediatric solid-organ transplant recipients carry chronic loads of Epstein-Barr virus exclusively in the immunoglobulin D-negative B-cell compartment.
Solid-organ transplant recipients are at risk for development of lymphoproliferative diseases. The purpose of this study was to examine the distribution of Epstein-Barr virus (EBV) load in the peripheral blood of pediatric transplant recipients who had become chronic viral load carriers (>8 copies/10(5) lymphocytes for >2 months). A total of 19 patients with viral loads ranging from 20 to 5,000 viral genome copies/10(5) lymphocytes were studied. Ten patients had no previous diagnosis of posttransplant lymphoproliferative disease (PT-LPD), while nine had recovered from a diagnosed case of PT-LPD. No portion of the peripheral blood viral load was detected in the cell-free plasma fraction. Viral DNA was found in a population of cells characterized as CD19(hi) and immunoglobulin D negative, a phenotype that is consistent with the virus being carried exclusively in the memory B-cell compartment of the peripheral blood. There was no difference in the compartmentalization based upon either the level of the viral load or the past diagnosis of an episode of PT-LPD. These results have implications for the design of tests to detect EBV infection and for the interpretation and use of positive EBV PCR assays in the management of transplant recipients.


Neuroleptic intolerance in patients with anti-NMDAR encephalitis.
To precisely describe the initial psychiatric presentation of patients with anti-NMDA receptor (NMDAR) antibodies encephalitis (anti-NMDAR encephalitis) to identify potential clues enhancing its early diagnosis. We retrospectively studied the French Reference Centre medical records of every adult patient with anti-NMDAR encephalitis to specify the patients' initial psychiatric symptoms leading to hospitalization in a psychiatric department and the reasons underlying the diagnosis of anti-NMDAR encephalitis. The medical records of 111 adult patients were reviewed. Psychiatric features were the initial presentation in 65 patients (59%). Among them, several psychiatric manifestations were observed, including visual and auditory hallucinations (n = 26, 40%), depression (n = 15, 23%), mania (n = 5, 8%), acute schizoaffective episode (n = 15, 23%), and eating disorder or addiction (n = 4; 6%). Forty-five patients (40% of total cohort) were first hospitalized in a psychiatric institution (91% women), with a median duration of stay of 9 days (range 0.25-239 days). Among them, 24 patients (53%) had associated discreet neurologic signs at the first evaluation, while 17 additional patients (38%) developed neurologic signs within a few days. Twenty-one patients (47%) were transferred to a medical unit for a suspicion of antipsychotic intolerance characterized by high temperature, muscle rigidity, mutism or coma, and biological results suggesting rhabdomyolysis. Several psychiatric presentations were observed in patients with anti-NMDAR encephalitis, although none was specific; however, patients, mostly women, also had discreet neurologic signs that should be carefully assessed as well as signs of antipsychotic intolerance that should raise suspicion for anti-NMDAR encephalitis.


[Surgical tactics in acute epididymitis in children].
Differentiated surgical policy was applied in the treatment of 147 children aged under 18 years with acute epididymitis. Basing on laboratory, clinical and ultrasound characteristics, three treatment methods were used: conservative treatment, puncture of the scrotum, revision of the scrotum. Puncture treatment of acute epididymitis appeared effective in accurate diagnosis of indications for this therapy and due performance. Ultrasound potential is shown in differential diagnosis in acute scrotum syndrome.


Causes and management of drug-induced long QT syndrome.
Long QT syndrome (LQTS) is characterized by inherited or acquired prolonged QT interval on the surface electrocardiogram. This can lead to torsade de pointes ventricular tachycardia (TdP VT) and ventricular fibrillation. In the acquired form of the disease, medications from several classes can cause TdP VT or potentiate the electrocardiographic findings. These include class IA and III antiarrhythmics, antibiotics (macrolides and quinolones), antidepressants (tricyclics and selective serotonin reuptake inhibitors), antipsychotics (haloperidol and phenothiazines), and antiemetics (ondansetron and prochlorperazine). We present four cases of drug-induced LQTS resulting in life-threatening cardiac arrhythmias. Antiarrhythmic medications were the cause in two cases, and the other two cases involved noncardiac medications. All four patients had at least one risk factor for LQTS in addition to the offending drug, including female gender, hypokalemia, hypomagnesemia, and bradycardia. In one patient, amiodarone was administered for treatment of VT, although the correct diagnosis was actually TdP VT. In patients with polymorphic VT or ventricular fibrillation without a significant history of cardiovascular disease, drug-induced LQTS should be high in the differential diagnosis. Prompt diagnosis is key, as amiodarone, while often used to suppress VT, is potentially harmful in the setting of LQTS and TdP VT.


Pleiotrophin promotes perineural invasion in pancreatic cancer.
Perineural invasion (PNI) in pancreatic cancer is an important cause of local recurrence, but little is known about its mechanism. Pleiotrophin (PTN) is an important neurotrophic factor. It is of interest that our recent experimental data showed its involvement in PNI of pancreatic cancer. PTN strongly presents in the cytoplasm of pancreatic cancer cells, and high expression of PTN and its receptor may contribute to the high PNI of pancreatic cancer. Correspondingly, PNI is prone to happen in PTN-positive tumors. We thus hypothesize that, as a neurite growth-promoting factor, PTN may promote PNI in pancreatic cancer. PTN is released at the time of tumor cell necrosis, and binds with its high-affinity receptor, N-syndecan on pancreatic nerves, to promote neural growth in pancreatic cancer. Furthermore, neural destruction leads to a distorted neural homeostasis. Neurons and Schwann cells produce more N-syndecan in an effort to repair the pancreatic nerves. However, the abundance of N-syndecan attracts further PTN-positive cancer cells to the site of injury, creating a vicious cycle. Ultimately, increased PTN and N-syndecan levels, due to the continuous nerve injury, may promote cancer invasion and propagation along the neural structures. Therefore, it is meaningful to discuss the relationship between PTN/N-syndecan signaling and PNI in pancreatic cancer, which may lead to a better understanding of the mechanism of PNI in pancreatic cancer.


Features of uterine fibroids treated by abdominal myomectomy at Nnewi, Nigeria.
Seventy-two women with symptomatic uterine fibroids were treated by abdominal myomectomy from January 1994 to December 1996. Important features were a mean age of 32.3 years (range 25-49 years) and parity of 0 to 6; 83% ( n = 60) were nulliparous and 68% ( n = 49) were unmarried. The average estimated blood loss was 480 ml with 1.6 g/dl mean haemoglobin drop and 15.3% required blood transfusion. Complications were mild and infrequent; 7% ( n = 5) had mild wound infection and 16.7% ( n 12) had a febrile complication. The average hospital stay was 8.1 days. There was no mortality. In this study, symptomatic uterine fibroids requiring abdominal myomectomy predominantly affected young women who were mainly unmarried and nulliparous. Although the the operation was safe and well tolerated, preoperative GnRH(a) is recommended to reduce fibroid size and need for blood transfusion.


Current strategies to guarantee the authenticity of coffee.
As they become more health conscious, consumers are paying increasing attention to food quality and safety. In coffee production, fraudulent strategies to reduce costs and maximize profits include mixing beans from two species of different economic value, the addition of other substances and/or foods, and mislabeling. Therefore, testing for coffee authenticity and detecting adulterants is required for value assessment and consumer protection. Here we provide an overview of the chromatography, spectroscopy, and single-nucleotide polymorphism-based methods used to distinguish between the major coffee species Arabica and Robusta. This review also describes the techniques applied to trace the geographical origin of coffee, based mainly on the chemical composition of the beans, an approach that can discriminate between coffee-growing regions on a continental or more local level. Finally, the analytical techniques used to detect coffee adulteration with other foods and/or coffee by-products are discussed, with a look at the practice of adding pharmacologically active compounds to coffee, and their harmful effects on health.