Scan, extract, wrap, compute-a 3D method to analyse morphological shape differences.
Quantitative analysis of shape and form is critical in many biological disciplines, as context-dependent morphotypes reflect changes in gene expression and physiology, e.g., in comparisons of environment-dependent phenotypes, forward/reverse genetic assays or shape development during ontogenesis. 3D-shape rendering methods produce models with arbitrarily numbered, and therefore non-comparable, mesh points. However, this prevents direct comparisons. We introduce a workflow that allows the generation of comparable 3D models based on several specimens. Translocations between points of modelled morphotypes are plotted as heat maps and statistically tested. With this workflow, we are able to detect, model and investigate the significance of shape and form alterations in all spatial dimensions, demonstrated with different morphotypes of the pond-dwelling microcrustacean Daphnia. Furthermore, it allows the detection even of inconspicuous morphological features that can be exported to programs for subsequent analysis, e.g., streamline- or finite-element analysis.


Current status of the human malformation map.
The recent advances in recombinant DNA technology are now being applied to map and clone the genes for dysmorphic syndromes. The genes for almost 40% of the malformation and dysplasia syndromes listed in Smith's Recognizable Patterns of Human Malformation [Jones, 1988] have now been mapped and/or identified. This strategy has dramatically changed the way in which clinical geneticists look at the basic mechanisms of genetic disorders. The primary purpose of applying positional cloning to human disease, including malformation syndromes, is to use the cloned gene to understand the basic pathogenesis of the disorder at hand. The importance of the application of knowledge of mouse models, to human molecular biology and the significance of the role of the clinician in documenting astute observations that assist in mapping cannot be overemphasized. Many of the successful outcomes in gene cloning in dysmorphic syndromes that have occurred thus far were clearly helped by the recognition of patients with chromosomal rearrangements. Collaboration of molecular biologists and clinical geneticists will clearly lead to the continued elucidation of the map location and cloned gene of many other disorders.


Complement Component C3 Variant (R102G) and the Risk of Neovascular Age-Related Macular Degeneration in a Tunisian Population.
Purpose To explore the association between the polymorphism (S/F) p.R102G in the complement component 3 (C3) gene and age-related macular degeneration (AMD) in a Tunisian population. Methods The molecular study was performed by polymerase chain reaction using sequence-specific primers (PCR-SSP) in 207 control subjects free of any eye disease (fundus normal) and 145 patients with exudative AMD. The CH50 activity and quantification of C3 and C4 have been made by technical home method and nephelometry, respectively. Results The prevalence of C3 GG genotype polymorphism was significantly higher in AMD patients compared to controls (OR: 2.41, IC 95% [1.90-3.05], p = 0.0007). However, no correlation was found between this allelic variant and the type of neovascularization. Similarly, there is no association between this polymorphism and the presence of functional and/or quantitative hypocomplementemia. Conclusions The C3 GG genotype of the gene could be a susceptibility factor for AMD in the Tunisian population. However, it does not seem to influence the clinical profile of the disease.


Sleep position trainer versus tennis ball technique in positional obstructive sleep apnea syndrome.
Positional therapy (PT) is an effective therapy in positional obstructive sleep apnea syndrome (POSAS) when used, but the compliance of PT is low. The objective of this study was to investigate whether a new kind of PT is effective and can improve compliance. 29 patients were treated with the Sleep Position Trainer (SPT), 26 patients with the Tennis Ball Technique (TBT). At baseline and 1 month polysomnography, Epworth Sleepiness Scale (ESS) and the Quebec Sleep Questionnaire (QSQ) were taken. Daily compliance was objectively measured in both groups. Both therapies prevent supine sleep position to a median of 0% (min-max: SPT 0.0% to 67%, TBT 0.0% to 38.9%), resulting in a treatment success (AHI <5) in 68.0% of the SPT and 42.9% of the TBT patients. The ESS at baseline was <10 in both groups. Sleep quality parameters as wake after sleep onset (WASO; p = 0.001) and awakenings (p = 0.006) improved more in the SPT group. Total QSQ scores (0.4±0.2, p = 0.03) and the QSQ domains nocturnal symptoms (0.7±0.2, p = 0.01) and social interactions (0.8±0.3, p = 0.02) changed in favor of the SPT group. Effective compliance (≥4 h/night + ≥5 days/week) was 75.9% for the SPT and 42.3% for the TBT users (p = 0.01). In mild POSAS with normal EES the new SPT device and the standard TBT are equally effective in reducing respiratory indices. However, compared to the TBT, sleep quality, quality of life, and compliance improved significantly more in the SPT group.


Monocyte phenotype and cytokine production profiles are dysregulated by short-duration spaceflight.
Immune system dysregulation has been demonstrated to occur during and immediately following spaceflight. As the initial bias and magnitude for an immune response is heavily influenced by monocyte/macrophage secreted cytokines, this study investigated monocyte phenotype and cytokine production patterns following short-duration spaceflight. Secreted cytokine profiles were examined by cytometric bead array analysis of culture supernatants following whole blood culture activation with LPS or PMA+ionomycin. Nine short-duration Space Shuttle crewmembers participated in this study. Peripheral monocyte percentages were unaltered postflight. Constitutive monocyte expression of both CD62L and HLA-DR was reduced following spaceflight in a mission-specific fashion. Loss of either molecule indicates a functional disability of monocytes, either by inhibition of adhesion and tissue migration (CD62L) or by impaired antigen presentation (HLA-DR). Following LPS stimulation of monocytes, postflight expression of IL-6, TNFalpha, and IL-10 were significantly reduced (by 43%, 44%, and 41%, respectively) and expression of IL-1b was elevated (65%). IL-8 production was either elevated or reduced in a mission-specific fashion. Following PMA+ionomycin stimulation of all leukocyte populations, only expression of IL-6 was significantly reduced postflight. These data indicate that changes in monocyte constitutive phenotype and inflammatory cytokine production occur following short-duration spaceflight, which may impact overall crewmember immunocompetence. Also, monocyte/macrophage function may be highly sensitive to mission specific parameters.


Prevalence and genotypic characteristics of Clostridium difficile in a closed and integrated human and swine population.
Recently, an apparent rise in the number of cases attributed to community-acquired Clostridium difficile infection has led researchers to explore additional sources of infection. The finding of C. difficile in food animals and retail meat has raised concern about potential food-borne and occupational exposures. The objective of this study was to compare C. difficile isolated from a closed population of healthy individuals consisting of both humans and swine in order to investigate possible food safety and occupational risks for exposure. Using a multistep enrichment isolation technique, we identified 11.8% of the human wastewater samples and 8.6% of the swine samples that were positive for C. difficile. The prevalences of C. difficile in swine production groups differed significantly (P < 0.05); however, the prevalences in the two human occupational group cohorts did not differ significantly (P = 0.81). The majority of the human and swine isolates were similar based on multiple typing methods. The similarity in C. difficile prevalence in the human group cohorts suggests a low occupational hazard, while a greatly decreased prevalence of C. difficile in later-stage swine production groups suggests a diminished risk for food-borne exposure. The similarity of strains in the two host species suggests the possibility of a common environmental source for healthy individuals in a community setting.


Chronic Pelvic Pain in Women: A Review.
Chronic pelvic pain (CPP) is a challenging condition that affects an estimated 26% of the world's female population. Chronic pelvic pain accounts for 40% of laparoscopies and 12% of hysterectomies in the US annually even though the origin of CPP is not gynecologic in 80% of patients. Both patients and clinicians are often frustrated by a perceived lack of treatments. This review summarizes the evaluation and management of CPP using recommendations from consensus guidelines to facilitate clinical evaluation, treatment, improved care, and more positive patient-clinician interactions. Chronic pelvic pain conditions often overlap with nonpelvic pain disorders (eg, fibromyalgia, migraines) and nonpain comorbidities (eg, sleep, mood, cognitive impairment) to contribute to pain severity and disability. Musculoskeletal pain and dysfunction are found in 50% to 90% of patients with CPP. Traumatic experiences and distress have important roles in pain modulation. Complete assessment of the biopsychosocial factors that contribute to CPP requires obtaining a thorough history, educating the patient about pain mechanisms, and extending visit times. Training in trauma-informed care and pelvic musculoskeletal examination are essential to reduce patient anxiety associated with the examination and to avoid missing the origin of myofascial pain. Recommended treatments are usually multimodal and require an interdisciplinary team of clinicians. A single-organ pathological examination should be avoided. Patient involvement, shared decision-making, functional goal setting, and a discussion of expectations for long-term care are important parts of the evaluation process. Chronic pelvic pain is like other chronic pain syndromes in that biopsychosocial factors interact to contribute and influence pain. To manage this type of pain, clinicians must consider centrally mediated pain factors as well as pelvic and nonpelvic visceral and somatic structures that can generate or contribute to pain.


Intensive medicine - Guidelines on Parenteral Nutrition, Chapter 14.
In intensive care patients parenteral nutrition (PN) should not be carried out when adequate oral or enteral nutrition is possible. Critically ill patients without symptoms of malnutrition, who probably cannot be adequately nourished enterally for a period of <5 days, do not require full PN but should be given at least a basal supply of glucose. Critically ill patients should be nourished parenterally from the beginning of intensive care if they are unlikely to be adequately nourished orally or enterally even after 5-7 days. Critically ill and malnourished patients should, in addition to a possible partial enteral nutrition, be nourished parenterally. Energy supply should not be constant, but should be adapted to the stage, the disease has reached. Hyperalimentation should be avoided at an acute stage of disease in any case. Critically ill patients should be given, as PN, a mixture consisting of amino acids (between 0.8 and 1.5 g/kg/day), carbohydrates (around 60% of the non-protein energy) and fat (around 40% of the non-protein energy) as well as electrolytes and micronutrients.


A new Epeorus (Caucasiron) (Ephemeroptera: Heptageniidae) species from Turkey based on molecular and morphological evidence.
Epeorus (Caucasiron) turcicus sp. nov. is described based on larvae from NE Turkey. The new species can be distinguished from other Caucasiron by a unique combination of several diagnostic characters: the presence of a rounded hypodermal medial femur spot, colouration of abdominal terga and sterna, narrow gill plate VII, fine hair-like setae on the surface of abdominal terga, and absence of postero-lateral projections on tergum X. In addition to morphological analysis, two single-locus analytical approaches are employed for delimiting the new species using COI sequences (Automatic Barcode Gap Discovery, ABGD; and General Mixed Yule Coalescent Model, GMYC). Both approaches unambiguously recognized E. (C.) turcicus sp. nov. as a distinct species. Our molecular dataset contains all Caucasiron species occurring in the Caucasus and the delimitation of individual species mostly follows the morphologically defined species. This study confirms the suitability of the GMYC approach for species delimitation within Caucasiron.


Hydrolysis of plasma triacylglycerol-rich lipoproteins from immature and laying hens (Gallus domesticus) by lipoprotein lipase in vitro.
Very-low-density (VLD) lipoproteins and portomicrons were isolated from the plasma of immature and laying hens and their size, lipid composition and susceptibility to hydrolysis by lipoprotein lipase were compared. In agreement with other studies, VLD lipoproteins from laying hens were found to be smaller and have a different lipid composition than VLD lipoproteins from immature hens. Portomicrons from immature and laying hens had mean diameters of about 150 nm and similar lipid compositions. Hydrolysis of VLD lipoproteins from immature hens, and portomicrons from immature and laying hens, proceeded rapidly until at least 40% of the substrate had been used. In contrast only 1--15% of laying-hen VLD-lipoprotein triacylglycerol was readily hydrolysis occurred slowly. The limited susceptibility of laying-hen VLD lipoproteins appeared to be due to their low content of lipoprotein lipase activator apoprotein, which occurred despite an abundance of activator in the high-density lipoproteins of laying-hen plasma. The results provide further evidence that the liver of the laying hen synthesizes specialized lipoproteins. Their limited susceptibility to hydrolysis by lipoprotein lipase is probably a major factor in ensuring transport of lipid to yolk rather than to other tissues. The form of transport of dietary lipid, however, is similar in immature and laying hens.


Beneficial effects of diltiazem and propranolol, alone and in combination, in patients with stable angina pectoris.
The antianginal effects of diltiazem 180 mg/day and propranolol 240 mg/day, alone and in combination, were investigated in 15 patients with effort related angina in a double blind placebo controlled crossover trial, with each period of treatment lasting four weeks. Patients performed a symptom limited treadmill exercise test at the end of each period of treatment. Mean (SEM) time to onset of angina was increased from 293(32) s when receiving placebo to 347(38) s when receiving diltiazem alone, to 350(30) s when receiving propranolol alone, and further to 421(34) s when receiving diltiazem and propranolol combined. Similar changes occurred in the duration of exercise testing and time to 1 mm ST segment depression. The sum of ST segment depression at peak exercise was reduced by both diltiazem and propranolol alone compared with placebo, and combination treatment produced a further significant improvement. Rate pressure product was significantly reduced at rest and at peak exercise after propranolol alone and combination treatment. The study clearly showed the superior value of diltiazem and propranolol combined in effort related angina when compared with either drug used alone.


Investigation on gas permeability of compacted GMZ bentonite with consideration of variations in liquid saturation, dry density and confining pressure.
During the long term operation of a disposal repository, gas will be inevitably generated. Determination of gas permeability of compacted bentonite is of great importance for the safety assessment of the engineered barrier system. In the present work, the steady-state and residual pressure methods were employed to determine the gas permeability of GaoMiaoZi (GMZ) bentonite with consideration of variations in liquid saturation, dry density and confining pressure. Results show that, gas migration in saturated GMZ bentonite was mainly controlled by diffusion with an effective gas permeability of 1E-23 m2 - 1E-25 m2. While in unsaturated GMZ bentonite, significant gas flow rates could be observed, which increased stably with the increase of gas injection pressure. Klinkenberg effect was significant when gas flow through GMZ bentonite. The Klinkenberg corrected gas permeability decreased by 3.5-5.5 orders of magnitude as the liquid saturation increased from 10% to 70%. A decreasing magnitude of 1-2 orders in Klinkenberg corrected gas permeability was presented with the dry density increased from 1.5 Mg/m3 and 1.7 Mg/m3. The Klinkenberg corrected gas permeability decreased by 0-1 orders of magnitude as the confining pressure increased from 3 MPa to 7 MPa. By using the accessible porosity, gas measured intrinsic permeability could be determined with values ranged between 1E-15 m2 to 4E-15 m2, which was higher than the water measured one by 5 orders of magnitude. Additionally, a generalized power law was successfully adopted in this study to describe the evolution of gas relative permeability with the liquid saturation. Overall, the effective gas permeability, Klinkenberg corrected gas permeability, intrinsic and relative permeability determined in this study provided a comprehensive perspective to assess the buffering property of GMZ bentonite in multi-physical field coupling environment. The parameters obtained can be adopted in further simulation works for long-term safety analysis of the disposal repository from the viewpoint of gas migration.


Paraneoplastic pemphigus in association with Castleman's disease.
Paraneoplastic pemphigus (PNP) is an autoimmune mucocutaneous disease associated with lymphoproliferative neoplasms, and frequently with a very rare tumour, Castleman's disease. To analyse the clinical history, immunopathological and histopathological findings in 28 patients with a confirmed diagnosis of PNP and Castleman's disease. Sera from all patients were assayed by indirect immunofluorescence (IF) and immunoprecipitation (IP) for plakin autoantibodies, immunoblotting for detection of plectin autoantibodies, and enzyme-linked immunosorbent assay for detection of desmoglein (Dsg)1 and Dsg3 autoantibodies. Severe oral mucositis was observed in all patients, and lichenoid cutaneous lesions were seen in 19 of 28. Twenty cases of Castleman's disease were of the hyaline vascular type, four were of plasmacytoid type and four were of mixed type. Striking findings included pulmonary destruction leading to bronchiolitis obliterans in 26 patients and fatal outcome due to respiratory failure in 22 patients with pulmonary involvement. Histological findings included lichenoid and interface dermatitis with variable intraepithelial acantholysis. Direct IF showed deposition of IgG and C3 in the mouth and skin in 24 of 28 patients. However, indirect IF detected serum IgG autoantibodies in all patients. IP revealed IgG autoantibodies against desmoplakin I, envoplakin and periplakin in all cases, and against desmoplakin II and the 170-kDa antigen in 19 patients. Dsg3 and Dsg1 autoantibodies were present in 22 and 11 patients, respectively, and plectin autoantibodies in 23 patients. PNP in association with Castleman's disease presents with severe oral mucositis and cutaneous lichenoid lesions. Serum autoantibodies against plakin proteins are the most diagnostic markers. Pulmonary injury with respiratory failure is the cause of death in most cases.


C-reactive protein stimulates superoxide anion release and tissue factor activity in vivo.
C-reactive protein (CRP), the prototypic marker of inflammation, is a cardiovascular risk marker and recent in vitro studies suggest that it may promote atherogenesis. CRP promotes oxidative stress in vitro and induces tissue factor (TF) release. However, there is a paucity of data examining the effects of CRP on oxidative stress and tissue factor procoagulant activity (PCA) in vivo. Thus, we tested the effects of CRP administration on superoxide anion release and tissue factor activity and examined mechanistic pathways using a rat sterile air pouch model. Intraperitoneal administration of CRP (20mg/kg body weight) compared to human serum albumin (HuSA) increased superoxide anion release and tissue factor activity from peritoneal macrophages in vivo (p<0.01). This was confirmed using intrapouch administration of CRP (25mug/mL) compared to HuSA. Pretreatment with reactive oxygen species (ROS) scavengers or protein kinase C (PKC) inhibitor significantly abrogated CRP-induced superoxide anion release and tissue factor activity. Pretreatment with extracellular signal-regulated kinase (ERK) and Jun N-terminal kinase (JNK) inhibitors, but not p38 mitogen-activated protein kinase (p38MAPK) significantly decreased CRP-induced superoxide anion release from macrophages in vivo. CRP-induced tissue factor activity in vivo was abrogated by pretreatment with inhibitors to p38MAPK, JNK and NFkappab (nuclear factor-kappab), but not ERK. Antibodies to Fc gamma receptors, CD32 and CD64 resulted in significant reduction in CRP-induced superoxide and tissue factor activity in vivo. Thus, CRP appears to induce oxidative stress in vivo by stimulating NADPH oxidase via PKC, ERK and JNK phosphorylation, and induces tissue factor PCA in vivo via upregulation of PKC, p38MAPK, JNK, ROS and NFkappab. CRP-induced ROS appears to precede tissue factor release. These effects are abrogated by blocking Fc gamma receptors, CD32 and CD64. This in vivo demonstration provides further evidence for a role for CRP in atherothrombosis.


Reduced neural activity but improved coding in rodent higher-order visual cortex during locomotion.
Running profoundly alters stimulus-response properties in mouse primary visual cortex (V1), but its effect in higher-order visual cortex is under-explored. Here we systematically investigate how visual responses vary with locomotive state across six visual areas and three cortical layers using a massive dataset from the Allen Brain Institute. Although previous work has shown running speed to be positively correlated with neural activity in V1, here we show that the sign of correlations between speed and neural activity varies across extra-striate cortex, and is even negative in anterior extra-striate cortex. Nevertheless, across all visual cortices, neural responses can be decoded more accurately during running than during stationary periods. We show that this effect is not attributable to changes in population activity structure, and propose that it instead arises from an increase in reliability of single-neuron responses during locomotion.


Lesions and distribution of viral antigen following an experimental infection of young seronegative calves with virulent bovine virus diarrhea virus-type II.
During the past several years, acute infections with bovine viral diarrhea virus (BVDV) have been causally linked to hemorrhagic and acute mucosal disease-like syndromes with high mortality. The majority of BVDVs isolated in such cases have been classified as type II on the basis of genetic and antigenic characteristics. It was our objective to examine clinical disease, lesions and potential sites of viral replication, following experimental BVDV type II infection in young calves. On approximately day 35 after birth, calves that had received BVDV-antibody-negative colostrum were infected by intranasal inoculation of 5 x 10(5) TCID50 of BVDV type II isolate 24,515 in 5 mL of tissue culture fluid (2.5 mL/nostril). Calves were monitored twice daily for signs of clinical disease. Approximately 48-72 h after infection, all calves developed transient pyrexia (39.4-40.5 degrees C) and leukopenia. Beginning on approximately day 7 after infection, all calves developed watery diarrhea, pyrexia (40.5-41.6 degrees C), marked leukopenia (> or = 75% drop from preinoculation values), variable thrombocytopenia, and moderate to severe depression. Calves were euthanized on days 10, 11, or 12 after infection due to severe disease. Gross and histological lesions consisted of multifocal bronchointerstitial pneumonia (involving 10%-25% of affected lungs), bone marrow hypoplasia and necrosis, and minimal erosive lesions in the alimentary tract. Immunohistochemical staining for BVDV revealed widespread viral antigen usually within epithelial cells, smooth muscle cells and mononuclear phagocytes in multiple organs, including lung, Peyer's patches, gastric mucosa, thymus, adrenal gland, spleen, lymph nodes, bone marrow, and skin. This BVDV type II isolate caused rapidly progressive, severe multisystemic disease in seronegative calves that was associated with widespread distribution of viral antigen and few gross or histological inflammatory lesions.


Role of nasopharyngeal colonization with and without bacteremia in the protection of infant rats against Haemophilus influenzae type b challenge.
Nasopharyngeal colonization of infant rats with Haemophilus influenzae type b was investigated by two methods of intranasal inoculation. After traumatic instillation of the bacteria, 100% of the animals became colonized, compared with 75.5% of animals after atraumatic instillation. Among colonized rats, significantly more animals in the traumatic group developed bacteremia compared with those in the atraumatic group. Rats in the traumatic group had an onset of bacteremia at a mean of 2.6 days after inoculation compared with 7.3 days in the atraumatic group. The duration of colonization and bacteremia was the same in both groups. The majority of heavily colonized rats developed bacteremia compared with none of the lightly colonized rats. Thus, the development of bacteremia appeared to be related independently to both heavy colonization and traumatic instillation. Protection against intraperitoneal bacterial challenge with H. influenzae type b developed in rats that had been bacteremic; in the majority of animals, this correlated with the development of serum bactericidal activity. Protection and bactericidal activity were only rarely observed in nonbacteremic rats that had been either heavily or lightly colonized. The development of serum bactericidal activity was not related to either the duration or peak level of bacteremia. Thus, in this rat model, H. influenzae type b nasopharyngeal colonization without bacteremia did not appear to stimulate circulating antibodies that protected the animals against challenge.


A Tikhonov Regularization Scheme for Focus Rotations With Focused Ultrasound-Phased Arrays.
Phased arrays have a wide range of applications in focused ultrasound therapy. By using an array of individually driven transducer elements, it is possible to steer a focus through space electronically and compensate for acoustically heterogeneous media with phase delays. In this paper, the concept of focusing an ultrasound-phased array is expanded to include a method to control the orientation of the focus using a Tikhonov regularization scheme. It is then shown that the Tikhonov regularization parameter used to solve the ill-posed focus rotation problem plays an important role in the balance between quality focusing and array efficiency. Finally, the technique is applied to the synthesis of multiple foci, showing that this method allows for multiple independent spatial rotations.


Sex-discordant twins despite single embryo transfer: a report of two cases.
We report two extremely rare cases in which the patients delivered male and female infants that were dizygotic twins (DZT) despite single embryo transfer. Case 1: The patient was a 35-year-old woman with a 9-year history of unexplained infertility. In an oocyte retrieval cycle, one blastocyst was transferred; at 26 weeks of gestation, she delivered a 704-g female infant and a 420-g male infant by cesarean section. Because both infants were of extremely low birth weight, they were placed in the neonatal intensive care unit. Congenital anomalies were not found in either infant. Case 2: The patient was a 30-year-old woman with a 1-year history of infertility. Hysterosalpingogram revealed bilateral tubal occlusion. In a frozen/thawed cycle one blastocyst was transferred during her natural ovulation cycle. She achieved a pregnancy and delivered a 2,877-g female infant and a 2,544-g male infant at 36 weeks of gestation by cesarean section. The female infant was diagnosed with a neural tube defect. No congenital anomalies were detected in the male infant. We hypothesize that the DZTs might have been the result of concurrent embryo transfer and natural ovulation and intercourse.


Sharing notes with patients: A review of current practice and considerations for neurologists.
Improved patient engagement is a critical consideration in the new payment climate. Releasing progress notes for patients to view may improve patient involvement and engagement in their care. Patients perceive benefit from viewing physician progress notes. As initial studies involved only primary care physicians, specialist physicians may have specific considerations when releasing notes to patients. This article provides a framework for neurologists to implement a note release policy in their practice.


Repeatability of FDG PET/CT metrics assessed in free breathing and deep inspiration breath hold in lung cancer patients.
We measured the repeatability of FDG PET/CT uptake metrics when acquiring scans in free breathing (FB) conditions compared with deep inspiration breath hold (DIBH) for locally advanced lung cancer. Twenty patients were enrolled in this prospective study. Two FDG PET/CT scans per patient were conducted few days apart and in two breathing conditions (FB and DIBH). This resulted in four scans per patient. Up to four FDG PET avid lesions per patient were contoured. The following FDG metrics were measured in all lesions and in all four scans: Standardized uptake value (SUV)peak, SUVmax, SUVmean, metabolic tumor volume (MTV) and total lesion glycolysis (TLG), based on an isocontur of 50% of SUVmax. FDG PET avid volumes were delineated by a nuclear medicine physician. The gross tumor volumes (GTV) were contoured on the corresponding CT scans. Nineteen patients were available for analysis. Test-retest standard deviations of FDG uptake metrics in FB and DIBH were: SUVpeak FB/DIBH: 16.2%/16.5%; SUVmax: 18.2%/22.1%; SUVmean: 18.3%/22.1%; TLG: 32.4%/40.5%. DIBH compared to FB resulted in higher values with mean differences in SUVmax of 12.6%, SUVpeak 4.4% and SUVmean 11.9%. MTV, TLG and GTV were all significantly smaller on day 1 in DIBH compared to FB. However, the differences between metrics under FB and DIBH were in all cases smaller than 1 SD of the day to day repeatability. FDG acquisition in DIBH does not have a clinically relevant impact on the uptake metrics and does not improve the test-retest repeatability of FDG uptake metrics in lung cancer patients.


Shape estimation of transparent objects by using inverse polarization ray tracing.
Few methods have been proposed to measure three-dimensional shapes of transparent objects such as those made of glass and acrylic. In this paper, we propose a novel method for estimating the surface shapes of transparent objects by analyzing the polarization state of the light. Existing methods do not fully consider the reflection, refraction, and transmission of the light occurring inside a transparent object. We employ a polarization raytracing method to compute both the path of the light and its polarization state. Polarization raytracing is a combination of conventional raytracing, which calculates the trajectory of light rays, and Mueller calculus, which calculates the polarization state of the light. First, we set an initial value of the shape of the transparent object. Then, by changing the shape, the method minimizes the difference between the input polarization data and the rendered polarization data calculated by polarization raytracing. Finally, after the iterative computation is converged, the shape of the object is obtained. We also evaluate the method by measuring some real transparent objects.


Prognostic value of emerging neurohormones in chronic heart failure during optimization of heart failure-specific therapy.
Serial measurements of neurohormones have been shown to improve prognostication in the setting of acute heart failure (HF) or chronic HF without therapeutic intervention. We investigated the prognostic role of serial measurements of emerging neurohormones and BNP in a cohort of chronic HF patients undergoing increases in HF-specific therapy. In this prospective study we included 181 patients with chronic systolic HF after an episode of hospitalization for worsening HF. Subsequently, HF therapy was gradually increased in the outpatient setting until optimized. We measured copeptin, midregional proadrenomedullin, C-terminal endothelin-1 precursor fragment, midregional proatrial natriuretic peptide, and B-type natriuretic peptide before and after optimization of HF therapy. The primary endpoint was all-cause mortality at 24 months. Angiotensin-converting enzyme/angiotensin receptor blocker and beta-blockers were increased significantly during the 3-month titration period (P < 0.0001 for both). In a stepwise Cox regression analysis adjusted for age, sex, glomerular filtration rate, diabetes mellitus, and ischemic HF, baseline and follow-up neurohormone concentrations were predictors of the primary endpoint as follows (baseline hazard ratios): copeptin 1.92, 95% CI 1.233-3.007, P = 0.004; midregional proadrenomedullin 2.79, 95% CI 1.297-5.995, P = 0.009; midregional proatrial natriuretic peptide 2.05, 95% CI 1.136-3.686, P = 0.017; C-terminal endothelin-1 precursor fragment 2.24, 95% CI 1.133-4.425, P = 0.025; B-type natriuretic peptide 1.46, 95% CI 1.039-2.050, P = 0.029. In pharmacologically unstable chronic HF patients, baseline values and follow-up measures of copeptin, midregional proadrenomedullin, C-terminal endothelin-1 precursor fragment, midregional proatrial natriuretic peptide, and B-type natriuretic peptide were equally predictive of all-cause mortality. Relative change of neurohormone values was noncontributory.


A role for the Saccharomyces cerevisiae ATX1 gene in copper trafficking and iron transport.
The ATX1 gene of Saccharomyces cerevisiae was originally identified as a multi-copy suppressor of oxidative damage in yeast lacking superoxide dismutase. We now provide evidence that Atx1p helps deliver copper to the copper requiring oxidase Fet3p involved in iron uptake. atx1Delta null mutants are iron-deficient and are defective in the high affinity uptake of iron. These defects due to ATX1 inactivation are rescued by copper treatment, and the same has been reported for strains lacking either the cell surface copper transporter, Ctr1p, or the putative copper transporter in the secretory pathway, Ccc2p. Atx1p localizes to the cytosol, and our studies indicate that it functions as a carrier for copper that delivers the metal from the cell surface Ctr1p to Ccc2p and then to Fet3p within the secretory pathway. The iron deficiency of atx1 mutants is augmented by mutations in END3 blocking endocytosis, suggesting that a parallel pathway for intracellular copper trafficking is mediated by endocytosis. As additional evidence for the role of Atx1p in iron metabolism, we find that the gene is induced by the same iron-sensing trans-activator, Aft1p, that regulates CCC2 and FET3.


Mycoremediation potential of Aspergillus ochraceus NRRL 3174.
Mycoremediation is an important process that targets the removal of petroleum hydrocarbons by fungi. Fungi have advantages with their extensive enzymatic systems, rapid adaptation to toxic organic pollutants, and to adverse environmental conditions. In this study, the colorimetric method was used for the preliminary investigation of petroleum degradation with ten fungal strains. Petroleum degradation ability of spore suspension, live biomass (fungal pellet and disc) and cell-free culture supernatant of the potent A. ochraceus strain were investigated by gravimetric analysis. It was found that the fungal disc (94%) was more successful than the spore suspension (87%) in petroleum degradation under physiological conditions determined as pH:5.0, 1% of petroleum concentration, 5% (v/v) of inoculum concentration (with spore suspension) and 1 g/100 mL of inoculum amount (with fungal disc) and 7 days of the incubation period. The degradation rate constant and half-life period of spore suspension were calculated as 0.291 day-1 and t1/2 = 0.340 and of the fungal disc were 0.401 day-1 and t1/2 = 0.247. Although, 7.5% and 10% (v/v) concentration of cell-free culture supernatant achieved more than 80% petroleum removal, it was not as effective as a fungal disc. According to gas chromatography/mass spectrometry analysis, the fungal disc of A. ochraceus strain degraded long-chain n-alkanes such as C35 and C36 more effectively than n-alkanes in the range of C22-C34. The fact that the A. ochraceus NRRL 3174 strain has a high petroleum degradation capacity as well as being a potent biosurfactant producer will provide a different perspective to advanced mycoremediation studies.


Evidence of decreased gap junction coupling between astrocytes and oligodendrocytes in the anterior cingulate cortex of depressed suicides.
Glial dysfunction is a major pathophysiological feature of mood disorders. While altered astrocyte (AS) and oligodendrocyte-lineage (OL) functions have been associated with depression, the crosstalk between these glial cell types has never been assessed in that context. AS are potent regulators of myelination, in part through gap junction (GJ) channels formed by the heterotypic coupling of AS-specific (Cx30 and Cx43) and OL-specific (Cx32 and Cx47) connexins. This study therefore aimed at addressing the integrity of AS/OL coupling in the anterior cingulate cortex (ACC) of depressed suicides. Using immunofluorescence and confocal imaging, we characterized the distribution of Cx30 and mapped its expression onto OL somas, myelinated axons, and brain vasculature in postmortem brain samples from depressed suicides (N = 48) and matched controls (N = 23). Differential gene expression of key components of the GJ nexus was also screened through RNA-sequencing previously generated by our group, and validated by quantitative real-time PCR. We show that Cx30 expression localized onto OL cells and myelinated fibers is decreased in deep cortical layers of the ACC in male-depressed suicides. This effect was associated with decreased expression of OL-specific connexins, as well as the downregulation of major connexin-interacting proteins essential for the scaffolding, trafficking, and function of GJs. These results provide a first evidence of impaired AS/OL GJ-mediated communication in the ACC of individuals with mood disorders. These changes in glial coupling are likely to have significant impact on brain function, and may contribute to the altered OL function previously reported in this brain region.


Routine drain placement in Roux-en-Y gastric bypass: an expanded retrospective comparative study of 755 patients and review of the literature.
Routine drain use after laparoscopic Roux-en-y gastric bypass (LRYGB) is still practiced by many bariatric surgeons. After a patient in our program experienced intestinal obstruction secondary to a drain, we reevaluated our practice and hypothesized drains would be of no benefit and potentially harmful after LRYGB. Retrospective record review of all patients undergoing LRYGB from August 2005 to August 2009 was performed. As we changed our practice in December 2006, we have two comparable groups: one with a drain placed at surgery and one without. All operations were otherwise performed in an identical fashion by three fellowship-trained university surgeons. We compared outcomes between the two groups, particularly regarding gastrojejunal (GJ) leaks. Jejunojejunal (JJ) leaks, unlikely to be captured by these drains, were not studied. A total of 755 LRYGBs were performed during the study period, the first 272 patients with routine drains and the subsequent 483 without. Demographics were statistically similar between the two groups. There were four GJ leaks in the drain group (1.47%) and three in the nondrain group (0.62%). Among the drain patients, two required operation and two were treated nonoperatively. Among the nondrain patients, two required operation and one was treated nonoperatively. The leak and reoperation rates between the groups were not statistically different (p = 0.154 and p = 0.514). Routine drains likely have no benefit after LRYGB. Clinical parameters such as tachycardia, fever, oliguria, and increasing abdominal pain should guide further investigation for and treatment of a leak.


Physiological and cell morphology adaptation of Bacillus subtilis at near-zero specific growth rates: a transcriptome analysis.
Nutrient scarcity is a common condition in nature, but the resulting extremely low growth rates (below 0.025 h(-1) ) are an unexplored research area in Bacillus subtilis. To understand microbial life in natural environments, studying the adaptation of B. subtilis to near-zero growth conditions is relevant. To this end, a chemostat modified for culturing an asporogenous B. subtilis sigF mutant strain at extremely low growth rates (also named a retentostat) was set up, and biomass accumulation, culture viability, metabolite production and cell morphology were analysed. During retentostat culturing, the specific growth rate decreased to a minimum of 0.00006 h(-1) , corresponding to a doubling time of 470 days. The energy distribution between growth and maintenance-related processes showed that a state of near-zero growth was reached. Remarkably, a filamentous cell morphology emerged, suggesting that cell separation is impaired under near-zero growth conditions. To evaluate the corresponding molecular adaptations to extremely low specific growth, transcriptome changes were analysed. These revealed that cellular responses to near-zero growth conditions share several similarities with those of cells during the stationary phase of batch growth. However, fundamental differences between these two non-growing states are apparent by their high viability and absence of stationary phase mutagenesis under near-zero growth conditions.


Acetylated Histone H3K9 is associated with meiotic recombination hotspots, and plays a role in recombination redundantly with other factors including the H3K4 methylase Set1 in fission yeast.
Histone modifications are associated with meiotic recombination hotspots, discrete sites with augmented recombination frequency. For example, trimethylation of histone H3 lysine4 (H3K4me3) marks most hotspots in budding yeast and mouse. Modified histones are known to regulate meiotic recombination partly by promoting DNA double-strand break (DSB) formation at hotspots, but the role and precise landscape of involved modifications remain unclear. Here, we studied hotspot-associated modifications in fission yeast and found general features: acetylation of H3 lysine9 (H3K9ac) is elevated, and H3K4me3 is not significantly enriched. Mutating H3K9 to non-acetylatable alanine mildly reduced levels of the DSB-inducing protein Rec12 (the fission yeast homologue of Spo11) and DSB at hotspots, indicating that H3K9ac may be involved in DSB formation by enhancing the interaction between Rec12 and hotspots. In addition, we found that the lack of the H3K4 methyltransferase Set1 generally increased Rec12 binding to chromatin but partially reduced DSB formation at some loci, suggesting that Set1 is also involved in DSB formation. These results suggest that meiotic DSB formation is redundantly regulated by multiple chromatin-related factors including H3K9ac and Set1 in fission yeast.


Class I/Class II HLA Evolutionary Divergence Ratio Is an Independent Marker Associated With Disease-Free and Overall Survival After Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia.
Class I Human Leukocyte Antigen (HLA) evolutionary divergence (HED) is a metric which reflects immunopeptidome diversity and has been associated with immune checkpoint inhibitor responses in solid tumors. Its impact and interest in allogeneic hematopoietic stem cell transplantation (HCT) have not yet been thoroughly studied. This study analyzed the clinical and immune impact of class I and II HED in 492 acute myeloid leukemia (AML) recipients undergoing HCT. The overall cohort was divided into a training (n=338) and a testing (n=132) set. Univariate cox screening found a positive impact of a high class I HED and a negative impact of a high class II HED on both disease-free (DFS) and overall survival (OS). These results were combined in a unique marker, class I/class II HED ratio, and assessed in the testing cohort. The final multivariate cox model confirmed the positive impact of a high versus low class I/class II HED ratio on both DFS (Hazard Ratio (HR) 0.41 [95% CI 0.2-0.83]; p=0.01) and OS (HR 0.34 [0.19-0.59]; p<0.001), independently of HLA matching and other HCT parameters. No significant association was found between the ratio and graft-versus-host disease (GvHD) nor with neutrophil and platelet recovery. A high class I HED was associated with a tendency for an increase in NK, CD8 T-cell, and B cell recovery at 12 months. These results introduce HED as an original and independent prognosis marker reflecting immunopeptidome diversity and alloreactivity after HCT.


Principal Components Analysis on the spectral Bidirectional Reflectance Distribution Function of ceramic colour standards.
The Bidirectional Reflectance Distribution Function (BRDF) is essential to characterize an object's reflectance properties. This function depends both on the various illumination-observation geometries as well as on the wavelength. As a result, the comprehensive interpretation of the data becomes rather complex. In this work we assess the use of the multivariable analysis technique of Principal Components Analysis (PCA) applied to the experimental BRDF data of a ceramic colour standard. It will be shown that the result may be linked to the various reflection processes occurring on the surface, assuming that the incoming spectral distribution is affected by each one of these processes in a specific manner. Moreover, this procedure facilitates the task of interpolating a series of BRDF measurements obtained for a particular sample.


Coronary events complicating infective endocarditis.
Acute coronary syndromes (ACS) are a rare complication of infective endocarditis (IE). Only case reports and small studies have been published to date. We report the largest series of ACS in IE. The aim of our study was to describe the incidence and mechanisms of ACS associated with IE, to assess their prognostic impact and to describe their management. In a bicentre prospective observational cohort study, all patients with a definite diagnosis of IE were prospectively included. The incidence, mechanism and prognosis of patients with ACS were studied. Among 1210 consecutive patients with definite IE, 26 patients (2.2%) developed an ACS. Twenty-three patients (88%) had a coronary embolism. Two patients had coronary compression by an abscess or a pseudoaneurysm and one patient had an obstruction of his bioprosthesis and left coronary ostium by a large vegetation. Nineteen (73%) patients with ACS developed heart failure and this complication was 2.5 times more frequent than in patients without ACS (p<0.0001). In the ACS population, mortality rate was twice than the population without ACS. ACS is a rare complication of IE but is associated with an increased risk of heart failure and high mortality rate.


Where is the moving object now? Judgments of instantaneous position show poor temporal precision (SD = 70 ms).
Humans can precisely judge relative location between two objects moving with the same speed and direction, as numerous studies have shown. However, the precision for localizing a single moving object relative to stationary references remains a neglected topic. Here, subjects reported the perceived location of a moving object at the time of a cue. The variability of the reported positions increased steeply with the speed of the object, such that the distribution of responses corresponds to the distance that the object traveled in 70 ms. This surprisingly large temporal imprecision depends little on the characteristics of the trajectory of the moving object or of the cue that indicates when to judge the position. We propose that the imprecision reflects a difficulty in identifying which position of the moving object occurs at the same time as the cue. This high-level process may involve the same low temporal resolution binding mechanism that, in other situations, pairs simultaneous features such as color and motion.


Fatty acid synthase: a metabolic oncogene in prostate cancer?
In 1920, Warburg suggested that tumors consistently rely on anaerobic pathways to convert glucose to ATP even in the presence of abundant oxygen [Warberg, 1956] despite the fact that it is less efficient for energy supply than aerobic glycolysis. The reasons for this remain obscure to date. More often than not, the microenvironment of solid tumors contains regions of poor oxygenation and high acidity. In this context hypoxia can act in an epigenetic fashion, inducing changes in gene expression and in metabolism for survival. It is reasonable to assume that only the tumor cells capable of developing an unusual tolerance to limiting oxygen availability and to the acidosis resulting from excessive lactate production, can survive. In addition to the striking changes that occur in glucose metabolism, studies in human cancer patients suggest that there is often also an increase in free fatty acid turnover, oxidation and clearance [Legaspi et al., 1987; Hyltander et al., 1991]. For instance, a lipid mobilizing factor produced by tumor cells appears to be responsible for the increase in whole body fatty acid oxidation [Russell and Tisdale, 2002]. Fatty acids synthesis in tumor tissues also occurs at very high rates, as first demonstrated more than half a century ago [Medes et al., 1953]. Importantly, (14)C glucose studies have shown that in tumor cells almost all fatty acids derive from de novo synthesis despite adequate nutritional supply [Sabine and Abraham, 1967; Ookhtens et al., 1984; Weiss et al., 1986]. In addition, tumors overexpressing fatty acid synthase (FAS), the enzyme responsible for de novo synthesis of fatty acids, display aggressive biologic behavior compared to those tumors with normal FAS levels, suggesting that FAS overexpression confers a selective growth advantage. Here, we will review the roles that FAS plays in important cellular processes such as apoptosis and proliferation. In addition, speculations on the putative role of FAS in the altered metabolic pathways of prostate cancer cells will be explored. Because of the frequent overexpression of this enzyme prostate cancer, FAS constitutes a therapeutic target in this disease.


Variations in the temporal pattern of perforant pathway stimulation control the activity in the mesolimbic pathway.
Signal processing in the hippocampal formation and resultant signal propagation to cortical and subcortical structures during high frequency stimulation (i.e. 100 Hz) of the perforant pathway was studied in medetomidine anesthetized rats by functional magnetic resonance imaging (fMRI) and electrophysiological recordings. The perforant pathway was stimulated with bursts of 20 pulses, one burst per second, or with continuously applied pulses. The stimulation duration was adjusted to 8 s (short) or 30 s (long). In general, extending the stimulation duration only caused a local spreading of the fMRI response, but no changes in the magnitude of the fMRI response. This was in agreement with the electrophysiological responses, which also remained unchanged. In contrast, increasing the number of pulses in one stimulus train (i.e. changing from burst to continuous stimulation), caused both spreading and an increase in local fMRI responses that were accompanied by an altered neuronal response pattern. Continuous stimulation also triggered additional fMRI responses in the septum, nucleus accumbens, anterior cingulate cortex/medial prefrontal cortex, and ventral tegmental area/substantia nigra. The appearance of fMRI responses outside the hippocampal formation required at least 3 consecutive stimulation trains, characterized by region specific hemodynamic response functions. Thus, once triggered, continuous stimulation caused a sequential appearance in fMRI responses starting in the hippocampal formation, followed by signal changes in the ventral tegmental area/substantia nigra and anterior cingulate cortex/medial prefrontal cortex and eventually in the nucleus accumbens. These results indicate that high frequency stimulation of the hippocampal formation can activate the mesolimbic pathway, provided that repetitive stimulations are applied.


Sport and eating disorders - understanding and managing the risks.
There is strong and consistent evidence that eating disorders are prevalent in sport and especially in weight sensitive sports such as endurance, weight category and aesthetic sports as well as jumping events. These illnesses are not only common but lead to significant physical and psychological morbidity and impaired performances.Sports organizations, and by extension the professionals whose job it is to help and support athletes, have important roles in dealing with these conditions. Preventative practices can be adopted if there is an understanding of how the sports environment contributes to the development of eating disorders. Some disorders can be difficult to detect especially in a sports environment and simple screening instruments are available. Athletes may also need help to access appropriate treatment whilst they are recovering.In many sports prevention, screening and support programs have been developed for a variety of medical conditions or sportsrelated injuries. Similar programs should be developed for eating disorders.


Pilot and astronaut offspring: possible G-force effects on human sex ratio.
Ratio of male to female offspring in tactical pilots and astronauts who experienced G forces was compared to that of pilots and non-rated officers who were not exposed to such conditions. In the analysis presented here we found 62 pilots and astronauts exposed to higher G forces had a significantly lower ratio of males to females in their offspring (.40) than did 220 pilots and non-pilots who were not exposed to high G forces. Other studies have also reported a decreased sex ratio in offspring of men exposed to high G forces. Reduction in number of males produced by fathers routinely exposed to comparatively high-G stresses may be related to G-force effects on sperm. This study suggests high-G exposure may affect the reproduction process.


Magnesium for skeletal muscle cramps.
Skeletal muscle cramps are common and often occur in association with pregnancy, advanced age, exercise or motor neuron disorders (such as amyotrophic lateral sclerosis). Typically, such cramps have no obvious underlying pathology, and so are termed idiopathic. Magnesium supplements are marketed for the prophylaxis of cramps but the efficacy of magnesium for this purpose remains unclear. This is an update of a Cochrane Review first published in 2012, and performed to identify and incorporate more recent studies. To assess the effects of magnesium supplementation compared to no treatment, placebo control or other cramp therapies in people with skeletal muscle cramps. SEARCH METHODS: On 9 September 2019, we searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase, LILACS, CINAHL Plus, AMED, and SPORTDiscus. We also searched WHO-ICTRP and ClinicalTrials.gov for registered trials that might be ongoing or unpublished, and ISI Web of Science for studies citing the studies included in this review. Randomized controlled trials (RCTs) of magnesium supplementation (in any form) to prevent skeletal muscle cramps in any patient group (i.e. all clinical presentations of cramp). We considered comparisons of magnesium with no treatment, placebo control, or other therapy. Two review authors independently selected trials for inclusion and extracted data. Two review authors assessed risk of bias. We attempted to contact all study authors when questions arose and obtained participant-level data for four of the included trials, one of which was unpublished. We collected all data on adverse effects from the included RCTs. We identified 11 trials (nine parallel-group, two cross-over) enrolling a total of 735 individuals, amongst whom 118 cross-over participants additionally served as their own controls. Five trials enrolled women with pregnancy-associated leg cramps (408 participants) and five trials enrolled people with idiopathic cramps (271 participants, with 118 additionally crossed over to control). Another study enrolled 29 people with liver cirrhosis, only some of whom suffered muscle cramps. All trials provided magnesium as an oral supplement, except for one trial which provided magnesium as a series of slow intravenous infusions. Nine trials compared magnesium to placebo, one trial compared magnesium to no treatment, calcium carbonate or vitamin B, and another trial compared magnesium to vitamin E or calcium. We judged the single trial in people with liver cirrhosis and all five trials in participants with pregnancy-associated leg cramps to be at high risk of bias. In contrast, we rated the risk of bias high in only one of five trials in participants with idiopathic rest cramps. For idiopathic cramps, largely in older adults (mean age 61.6 to 69.3 years) presumed to have nocturnal leg cramps (the commonest presentation), differences in measures of cramp frequency when comparing magnesium to placebo were small, not statistically significant, and showed minimal heterogeneity (I² = 0% to 12%). This includes the primary endpoint, percentage change from baseline in the number of cramps per week at four weeks (mean difference (MD) -9.59%, 95% confidence interval (CI) -23.14% to 3.97%; 3 studies, 177 participants; moderate-certainty evidence); and the difference in the number of cramps per week at four weeks (MD -0.18 cramps/week, 95% CI -0.84 to 0.49; 5 studies, 307 participants; moderate-certainty evidence). The percentage of individuals experiencing a 25% or better reduction in cramp rate from baseline was also no different (RR 1.04, 95% CI 0.84 to 1.29; 3 studies, 177 participants; high-certainty evidence). Similarly, no statistically significant difference was found at four weeks in measures of cramp intensity or cramp duration. This includes the number of participants rating their cramps as moderate or severe at four weeks (RR 1.33, 95% CI 0.81 to 2.21; 2 studies, 91 participants; moderate-certainty evidence); and the percentage of participants with the majority of cramp durations of one minute or more at four weeks (RR 1.83, 95% CI 0.74 to 4.53, 1 study, 46 participants; low-certainty evidence). We were unable to perform meta-analysis for trials of pregnancy-associated leg cramps. The single study comparing magnesium to no treatment failed to find statistically significant benefit on a three-point ordinal scale of overall treatment efficacy. Of the three trials comparing magnesium to placebo, one found no benefit on frequency or intensity measures, another found benefit for both, and a third reported inconsistent results for frequency that could not be reconciled. The single study in people with liver cirrhosis was small and had limited reporting of cramps, but found no difference in terms of cramp frequency or cramp intensity. Our analysis of adverse events pooled all studies, regardless of the setting in which cramps occurred. Major adverse events (occurring in 2 out of 72 magnesium recipients and 3 out of 68 placebo recipients), and withdrawals due to adverse events, were not significantly different from placebo. However, in the four studies for which it could be determined, more participants experienced minor adverse events in the magnesium group than in the placebo group (RR 1.51, 95% CI 0.98 to 2.33; 4 studies, 254 participants; low-certainty evidence). Overall, oral magnesium was associated with mostly gastrointestinal adverse events (e.g. diarrhoea), experienced by 11% (10% in control) to 37% (14% in control) of participants. It is unlikely that magnesium supplementation provides clinically meaningful cramp prophylaxis to older adults experiencing skeletal muscle cramps. In contrast, for those experiencing pregnancy-associated rest cramps the literature is conflicting and further research in this population is needed. We found no RCTs evaluating magnesium for exercise-associated muscle cramps or disease-state-associated muscle cramps (for example amyotrophic lateral sclerosis/motor neuron disease) other than a single small (inconclusive) study in people with liver cirrhosis, only some of whom suffered cramps.


Computationally Assisted Design of Polarizing Agents for Dynamic Nuclear Polarization Enhanced NMR: The AsymPol Family.
We introduce a new family of highly efficient polarizing agents for dynamic nuclear polarization (DNP)-enhanced nuclear magnetic resonance (NMR) applications, composed of asymmetric bis-nitroxides, in which a piperidine-based radical and a pyrrolinoxyl or a proxyl radical are linked together. The design of the AsymPol family was guided by the use of advanced simulations that allow computation of the impact of the radical structure on DNP efficiency. These simulations suggested the use of a relatively short linker with the intention to generate a sizable intramolecular electron dipolar coupling/ J-exchange interaction, while avoiding parallel nitroxide orientations. The characteristics of AsymPol were further tuned, for instance with the addition of a conjugated carbon-carbon double bond in the 5-membered ring to improve the rigidity and provide a favorable relative orientation, the replacement of methyls by spirocyclohexanolyl groups to slow the electron spin relaxation, and the introduction of phosphate groups to yield highly water-soluble dopants. An in-depth experimental and theoretical study for two members of the family, AsymPol and AsymPolPOK, is presented here. We report substantial sensitivity gains at both 9.4 and 18.8 T. The robust efficiency of this new family is further demonstrated through high-resolution surface characterization of an important industrial catalyst using fast sample spinning at 18.8 T. This work highlights a new direction for polarizing agent design and the critical importance of computations in this process.


Sumatriptan iontophoretic transdermal system: history, study results, and use in clinical practice.
Nausea is a common symptom of migraine, and current treatment guidelines recommend non-oral formulations for nauseated or vomiting patients. Transdermal delivery of sumatriptan, a 5-hydroxytryptamine1B1D agonist with established efficacy in patients with migraine, represents a novel approach to acute treatment. The sumatriptan iontophoretic transdermal system circumvents the gastrointestinal tract by using low-level electrical energy to transport sumatriptan across the skin. In multiple well-controlled studies, the sumatriptan transdermal system has shown that it provides consistent drug delivery with low interpatient variability, rapid relief of migraine pain and associated symptoms, and an excellent overall safety profile, with a low incidence of triptan-sensation adverse events. Patients and health care professionals who have used the sumatriptan transdermal system give it high ratings for ease of use/application. The sumatriptan transdermal system will allow a wide range of patients, especially those who experience migraine-related nausea or vomiting, to receive the benefits of migraine-specific therapy.


Cortical Structure and Cognition in Infants and Toddlers.
Cortical structure has been consistently related to cognitive abilities in children and adults, yet we know little about how the cortex develops to support emergent cognition in infancy and toddlerhood when cortical thickness (CT) and surface area (SA) are maturing rapidly. In this report, we assessed how regional and global measures of CT and SA in a sample (N = 487) of healthy neonates, 1-year-olds, and 2-year-olds related to motor, language, visual reception, and general cognitive ability. We report novel findings that thicker cortices at ages 1 and 2 and larger SA at birth, age 1, and age 2 confer a cognitive advantage in infancy and toddlerhood. While several expected brain-cognition relationships were observed, overlapping cortical regions were also implicated across cognitive domains, suggesting that infancy marks a period of plasticity and refinement in cortical structure to support burgeoning motor, language, and cognitive abilities. CT may be a particularly important morphological indicator of ability, but its impact on cognition is relatively weak when compared with gestational age and maternal education. Findings suggest that prenatal and early postnatal cortical developments are important for cognition in infants and toddlers but should be considered in relation to other child and demographic factors.


Educational interventions to improve hepatitis C testing or treatment in South Asian communities: A systematic review.
BACKGROUND: Hepatitis C (HCV) places a disproportionately higher burden on the South Asian community in comparison to the general population, despite the availability of effective antiviral therapies. This study seeks to characterize the effectiveness of health promotion initiatives aimed at South Asians to improve HCV prevention, education, screening, and treatment adherence. METHODS: A systematic review (PROSPERO: CRD42021253796) was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Ovid MEDLINE, CINAHL Plus, Web of Science, ERIC, Ovid Embase, Cochrane Library, and PsycINFO were searched from inception to 15 April 2022 for original studies that reported on any health promotion initiative directed at improving HCV outcomes in the South Asian community. Risk of bias was assessed via a quality score. RESULTS: A total of 15 studies (6 uncontrolled interventional, 3 before-after interventional, 3 randomized controlled, 2 prospective cohort, and 1 historically controlled interventional study designs) involving 69,958 participants were included. The most studied interventions were formal HCV teaching (n = 12), community outreach (n = 6), and coupling screening/testing with existing programs (n = 3). Ninety-two percent (14/15) of interventions were concluded to be successful, and 71% (10/14) of those were concluded to be feasible and/or cost-effective. CONCLUSIONS: Interventions that aim to improve HCV education and accessibility to screening/treatment can substantially reduce barriers to care in South Asian communities. Further research, of higher quality RCT evidence, is needed to study the long-term reduction in HCV prevalence from these proposed interventions, and their associated feasibility profiles.


Stent graft for nephrologists: concerns and consensus.
The role of the stent graft is emerging in the management of arteriovenous dialysis access. Physicians are incorporating this device in the management of three distinct problems--vein-graft anastomotic stenosis, pseudoaneurysm formation, and cephalic arch stenosis--with varying degrees of success. Indeed, a recent randomized, controlled trial to evaluate the role of angioplasty plus stent graft versus angioplasty alone for the management of stenosis at the vein-graft anastomosis led to the approval of the stent graft by the Food and Drug Administration; however, several elements of the management of stenosis at the vein-graft anastomosis/cephalic arch as well as the repair of pseudoaneurysms by stent graft remain controversial. The situation is further complicated and warrants a cost-to-benefit ratio analysis when the added cost of the device is appended to the procedure. In contrast to the controversies, angioplasty-induced complete vascular rupture is one situation in which a stent graft is indicated beyond any doubt. With recent conditional Food and Drug Administration approval, it is anticipated that the use of stent grafts might increase in our patients. In this context, it is critically important that nephrologists be familiar with the current controversies and consensus that surround the use of stent grafts for dialysis access. Just as therapeutic interventions are analyzed in other disciplines within nephrology, these experts must appraise the use of this device for dialysis access. This report presents an up-to-date synopsis on the use of the stent graft that would assist renal physicians in requesting or rejecting the device for the optimal management of their patient's vascular access dysfunction.


Parasite infection and cancer: with special emphasis on Schistosoma japonicum infections (Trematoda). A review.
This article contains a review of current knowledge on the association of parasite infections and cancer formation, especially that of Schistosoma japonicum (Trematoda) in man and experimental animals. The association of S. haematobium infection and bladder cancer is well known and documented. However, S. japonicum infection has also been reported to be associated with cancer, in this case hepatocellular carcinoma and/or colorectal cancer. Pathological records and analyses have shown a correlation between this infection and cancer, and pathohistological descriptions have been numerous, together with clinical case reports. Epidemiological analyses have been conducted in China and Japan and support a role of S. japonicum infection as one of the risk factors in cancer formation, along with others, such as hepatitis virus infection and alcoholic intake. Experimental results have also shown that cancer appears early and in larger numbers in experimentally infected animals given a known carcinogen. In spite of these positive end-point associations, the mechanism of schistosome-mediated enhancement of carcinogenesis is obscure. A suggestive observation is that in S. japonicum-infected mice carcinogen-metabolizing hepatic activity including P-450 was decreased so that an administered carcinogen persisted for a longer period than in uninfected mice. Further studies, both epidemiological and experimental, are needed to firmly establish the relationship between schistosome infection and cancer.


Amlodipine, clopidogrel and CYP3A5 genetic variability: effects on platelet reactivity and clinical outcomes after percutaneous coronary intervention.
To test the effect of a loss-of-function variation of the cytochrome P450 (CYP) 3A5 on drug-drug interaction between amlodipine and clopidogrel. Amlodipine is a well-known inhibitor of CYP 3A4, an isoenzyme of CYP3A that activates clopidogrel. However, controversy exists regarding whether amlodipine adversely affects clopidogrel response and clinical outcome after percutaneous coronary intervention (PCI). In the presence of CYP3A4 inhibitors such as amlodipine, the genetic variation of CYP3A5, the isoenzyme responsible for the backup CYP3A activity, may play an important role in clopidogrel activation. Post hoc analysis of a prospectively enrolled cohort. Patients enrolled in the CROSS-VERIFY cohort from June 2006 to June 2010, with successful genotyping of CYP3A5. The pharmacodynamic analysis end point was clopidogrel on-treatment platelet reactivity (OPR) and the clinical analysis end point was the composite of cardiac death, non-fatal myocardial infarction, ischaemic stroke and stent thrombosis at 12 months post-PCI. 1258 patients had successful genotyping and were categorised as CYP3A5 non-expressers (749 patients) and expressers (509 patients) according to the CYP3A5 genotype. Amlodipine users showed higher OPR versus non-users only in CYP3A5 non-expressers (249 ± 83 vs 228 ± 84 P2Y12 reaction units, p=0.013). These findings was corroborated by clinical outcomes, in which amlodipine users had a higher incidence of events compared with non-users only in CYP3A5 non-expressers (4.6% vs 0.6%, HR 7.731, CI 2.042 to 29.264, p=0.004). Treatment with amlodipine is associated with increased clopidogrel OPR and increased risk of thrombotic events after PCI, which is dependent on the CYP3A5 genetic status.


Facial Paralysis From Post-transplant Lymphoproliferative Disorder.
We report a case of facial paresis and profound hearing loss from post-transplant lymphoproliferative disorder (PTLD) in a pediatric patient with neuroblastoma. Three-year-old boy with rapidly progressive right facial paresis and sensorineural hearing loss. High-risk neuroblastoma had been diagnosed 1 year earlier, treated with chemotherapy and resection of the adrenal primary tumor. Two months after two autologous hematopoietic stem cell transplantations (HSCT), the patient developed facial paralysis. Magnetic resonance imaging (MRI) showed bilateral progressive internal auditory canal (IAC) enhancing lesions with a mass lesion on the right and wispy enhancement on the left and enhancement within the right cochlea. Lumbar puncture (LP) was positive for Epstein-Barr virus (EBV) making the diagnosis of PTLD most probable. Biopsy of the right IAC lesion was deferred because of potential procedural risks including intradural spread of tumor or fungus. The patient was treated with anti-fungal therapy and systemic rituximab without improvement. Subsequent intrathecal rituximab resulted in improvement of lesions on MRI and clearance of EBV from the cerebrospinal fluid (CSF). Mastoidectomy for biopsies from the mastoid and middle ear. Intrathecal treatment with rituximab. Imaging assessment of IAC lesion, CSF EBV titers, facial nerve function. Gradual resolution of IAC mass lesions, remission of PTLD, and facial improvement from House-Brackmann score of 4 to 3. PTLD causing facial paresis after autologous HSCT has not been previously reported and may be considered in the differential diagnosis of lesions causing facial paresis in patients who have received a stem cell or solid organ transplant.


Multiplexed Detection of Attomoles of Nucleic Acids Using Fluorescent Nanoparticle Counting Platform.
The sensitive multiplexed detection of nucleic acids in a single sample by a simple manner is of pivotal importance for the diagnosis and therapy of human diseases. Herein, we constructed an automatic fluorescent nanoparticle (FNP) counting platform with a common fluorescence microscopic imaging setup for nonamplification multiplexed detection of attomoles of nucleic acids. Taking the advantages of the highly bright, multicolor emitting FNPs and magnetic separation, the platform enables sensitive multiplexed detection without the need for extra fluorescent labels. Quantification for multiplex DNAs, multiplex microRNAs (miRNA), as well as a DNA and miRNA mixture was achieved with a similar dynamic range, a limit of detection down to 5 amol (5 μL detection volume), and a 81-115% spike recovery from different biological sample matrices. In particular, the sensitivity for multiplex miRNA is by far among the highest without using amplification or the lock nucleic acid hybridization enhancement strategy. Results regarding miRNA-141 from four different cell lines were agreeable with those of the quantitative reverse transcription polymerase chain reaction. Simultaneous detection of miRNA-141 and miRNA-21 in four different cell lines yielded consistent results with publications, indicating the potential for monitoring multiplex miRNA expression associated with the collaborative regulation of important cellular events. This work expands the rule set of multiplex nucleic acid detection strategies and shows promising potential application in clinical diagnosis.


OB Nest: Reimagining Low-Risk Prenatal Care.
Using a human-centered design method, our team sought to envision a new model of care for women experiencing low-risk pregnancy. This model, called OB Nest, aimed to demedicalize the experience of pregnancy by providing a supportive and empowering experience that fits within patients' daily lives. To explore this topic, we invited women to use self-monitoring tools, a text-based smartphone application to communicate with their care team, and moderated online communities to connect with other pregnant women. Through observations of tool use and patient- and care team-provided feedback, we found that self-measurement and access to a fetal heart monitor provided women with confidence and joy in the progress of their pregnancies while shifting their position to being an active participant in their care. The smartphone application gave women direct access to their care team, provided continuity, and removed hurdles in establishing communication. The online community platform was a space where women in the same obstetric clinic could share nonmedical questions and advice with one another. This created a sense of community, leveraged the knowledge of women, and provided a venue beyond the clinic visit for information exchange. These findings were integrated into the design of the Mayo Clinic OB Nest model. This model redistributes care based on the individual needs of patients by providing self-measurement tools and continuous flexible access to their care team. By enabling women to meaningfully participate in their care, there is potential for cost savings and improved patient satisfaction.


The role of the advanced practice nurse in neuroscience nursing: results of the 2006 AANN membership survey.
The need for a scope of practice for advanced practice neuroscience nurses was identified by the American Association of Neuroscience Nurses (AANN) in 2006. A task force consisting of advanced practice nurses (nurse practitioners and clinical nurse specialists) was commissioned by AANN and charged with the development of the document. Current information regarding the practices of advanced practice neuroscience nurses was needed as the task force began to develop this document. To best obtain this information, an electronic survey was created and distributed to advanced practice nurses within the AANN database. The survey questions included basic demographic data and sought information regarding activities and procedures performed by the advanced practice nurse. The results of this survey clearly reflect the diversity in practice and the integral role advanced practice neuroscience nurses play in the management of patients' care.


Heterogeneous drug penetrance of veliparib and carboplatin measured in triple negative breast tumors.
Poly(ADP-ribose) polymerase inhibitors (PARPi), coupled to a DNA damaging agent is a promising approach to treating triple negative breast cancer (TNBC). However, not all patients respond; we hypothesize that non-response in some patients may be due to insufficient drug penetration. As a first step to testing this hypothesis, we quantified and visualized veliparib and carboplatin penetration in mouse xenograft TNBCs and patient blood samples. MDA-MB-231, HCC70 or MDA-MB-436 human TNBC cells were implanted in 41 beige SCID mice. Low dose (20 mg/kg) or high dose (60 mg/kg) veliparib was given three times daily for three days, with carboplatin (60 mg/kg) administered twice. In addition, blood samples were analyzed from 19 patients from a phase 1 study of carboplatin + PARPi talazoparib. Veliparib and carboplatin was quantified using liquid chromatography-mass spectrometry (LC-MS). Veliparib tissue penetration was visualized using matrix-assisted laser desorption/ionization mass spectrometric imaging (MALDI-MSI) and platinum adducts (covalent nuclear DNA-binding) were quantified using inductively coupled plasma-mass spectrometry (ICP-MS). Pharmacokinetic modeling and Pearson's correlation were used to explore associations between concentrations in plasma, tumor cells and peripheral blood mononuclear cells (PBMCs). Veliparib penetration in xenograft tumors was highly heterogeneous between and within tumors. Only 35% (CI 95% 26-44%), 74% (40-97%) and 46% (9-37%) of veliparib observed in plasma penetrated into MDA-MB-231, HCC70 and MDA-MB-436 cell-based xenografts, respectively. Within tumors, penetration heterogeneity was larger with the 60 mg/kg compared to the 20 mg/kg dose (RSD 155% versus 255%, P = 0.001). These tumor concentrations were predicted similar to clinical dosing levels, but predicted tumor concentrations were below half maximal concentration values as threshold of response. Xenograft veliparib concentrations correlated positively with platinum adduct formation (R 2 = 0.657), but no PARPi-platinum interaction was observed in patients' PBMCs. Platinum adduct formation was significantly higher in five gBRCA carriers (ratio of platinum in DNA in PBMCs/plasma 0.64% (IQR 0.60-1.16%) compared to nine non-carriers (ratio 0.29% (IQR 0.21-0.66%, P < 0.0001). PARPi/platinum tumor penetration can be measured by MALDI-MSI and ICP-MS in PBMCs and fresh frozen, OCT embedded core needle biopsies. Large variability in platinum adduct formation and spatial heterogeneity in veliparib distribution may lead to insufficient drug exposure in select cell populations.


Patient and provider perspectives on adherence to and care coordination of lynch syndrome surveillance recommendations: findings from qualitative interviews.
Patients with a genetic variant associated with Lynch syndrome (LS) are recommended to undergo frequent and repeated cancer surveillance activities to minimize cancer-related morbidity and mortality. Little is known about how patients and primary care providers (PCPs) track and manage these recommendations. We conducted a small exploratory study of patient and PCP experiences with recommended LS surveillance activities and communication with family members in an integrated health care system. We used in-depth interviews with patients and providers to understand how surveillance is coordinated and monitored following confirmation of LS. We recruited patients with a range of ages/gender, and providers with at least at least one patient with a molecular diagnosis of LS. All interviews were recorded, transcribed, and content analyzed by a trained qualitative methodologist. Twenty-two interviews were completed with 12 patients and 10 providers. Most patients (10) had detailed knowledge of surveillance recommendations, but were less sure of time intervals. While all patients reported receiving initial education about their surveillance recommendations from a genetic counselor, seven did not follow-up with a genetic counselor in subsequent years. A third of patients described taking sole responsibility for managing their LS surveillance care. Lack of routine communication from the health system (e.g., prompts for surveillance activities), and provider engagement were surveillance barriers. PCPs were generally aware of LS, but had limited familiarity with surveillance recommendations. Most PCPs (7) viewed LS as rare and relied on patient and specialist expertise and support. Providers typically had 1 patient with LS in a panel of 1800 patients overall. Providers felt strongly that management of LS should be coordinated by a dedicated team of specialists. Most patients (92%) had at least one family member that sought LS testing, and common barriers for family members included lack of insurance, affordability, and fear of result. The maximal benefits of screening for confirmation of LS will only be realized with adherence to recommended preventive care. Important factors to ensure patients receive recommended LS care include a comprehensive and coordinated monitoring program that includes reminder prompts, and increased PCP education of LS and associated surveillance recommendations.


Metabolite and Transcriptome Profiling Analysis Revealed That Melatonin Positively Regulates Floral Scent Production in Hedychium coronarium.
Melatonin is a pleiotropic molecule that regulates a variety of developmental processes. Floral volatiles are important features of flowers that facilitate flower-visitor interactions by attracting pollinators, structure flower-visitor communities, and play defensive roles against plant and flower antagonists. Aside from their role in plants, floral volatiles are an essential ingredient in cosmetics, perfumes, pharmaceuticals, and flavorings. Herein, integrated metabolomic and transcriptomic approaches were carried out to analyze the changes triggered by melatonin exposure during the Hedychium coronarium flower development stages. Quantitative analysis of the volatiles of H. coronarium flowers revealed that volatile organic compound emission was significantly enhanced after melatonin exposure during the half bloom (HS), full bloom (FB) and fade stage (FS). Under the melatonin treatment, the emission of volatile contents was highest during the full bloom stage of the flower. Variable importance in projection (VIP) analysis and partial least-squares discriminant analysis (PLS-DA) identified 15 volatile compounds with VIP > 1 that were prominently altered by the melatonin treatments. According to the transcriptome sequencing data of the HS, FB, and FS of the flowers, 1,372, 1,510, and 1,488 differentially expressed genes were identified between CK-HS and 100MT-HS, CK-FB and 100MT-FB, and CK-FS and 100MT-FS, respectively. Among the significant differentially expressed genes (DEGs), 76 were significantly upregulated and directly involved in the floral scent biosynthesis process. In addition, certain volatile organic compounds were substantially linked with various DEGs after combining the metabolome and transcriptome datasets. Moreover, some transcription factors, such as MYB and bHLH, were also significantly upregulated in the comparison, which might be related to the floral aroma mechanism. Our results suggested that melatonin increased floral aroma production in H. coronarium flowers by modifying the expression level of genes involved in the floral scent biosynthesis pathway. These findings serve as a foundation for future research into the molecular mechanisms underlying the dynamic changes in volatile contents induced by melatonin treatment in H. coronarium.


Diabetic Peripheral Neuropathy Associated with Foot Ulcer: One of a Kind.
Significance: Diabetic peripheral neuropathy (DPN) associated with a diabetic foot ulcer (DFU) is likely to be complicated with critical factors such as biofilm infection and compromised skin barrier function of the diabetic skin. Repaired skin with a history of biofilm infection is known to be compromised in barrier function. Loss of barrier function is also observed in the oxidative stress affected diabetic and aged skin. Recent Advances: Loss of barrier function makes the skin prone to biofilm infection and cellulitis, which contributes to chronic inflammation and vasculopathy. Hyperglycemia favors biofilm formation as glucose lowering led to reduction in biofilm development. While vasculopathy limits oxygen supply, the O2 cost of inflammation is high increasing hypoxia severity. Critical Issues: The host nervous system can be inhabited by bacteria. Because electrical impulses are a part of microbial physiology, polymicrobial colonization of the host's neural circuit is likely to influence transmission of action potential. The identification of perineural apatite in diabetic patients with peripheral neuropathy suggests bacterial involvement. DPN starts in both feet at the same time. Future Directions: Pair-matched studies of DPN in the foot affected with DFU (i.e., DFU-DPN) compared with DPN in the without ulcer, and intact skin barrier function, are likely to provide critical insight that would help inform effective care strategies. This review characterizes DFU-DPN from a translational science point of view presenting a new paradigm that recognizes the current literature in the context of factors that are unique to DFU-DPN.


Microstructure formation in molecular and polymer semiconductors assisted by nucleation agents.
Additives, including nucleating agents, have been used to regulate the solidification process of (semi-)crystalline polymer solids and thus control both their crystallite dimensions and shape. Here, we demonstrate that minute amounts (0.1-1 wt%) of commercially available nucleating agents can be used to efficiently manipulate the solidification kinetics of a wide range of organic semiconductors--including poly(3-alkylthiophene)s, the fullerene derivative [6,6]-phenyl-C61-butyric acid methyl ester (PCBM) and 6,13-bis(triisopropyl-silylethynyl) (TIPS) pentacene--when processed from the melt, solution or solid state, without adversely affecting the semiconductors' electronic properties. Heterogeneous nucleation increases the temperature of and rate of crystallization of poly(3-alkylthiophene)s, permits patterning of crystallites at pre-defined locations in PCBM, and minimizes dewetting of films of TIPS-pentacene formed by inkjet printing. Nucleating agents thus make possible the fabrication of thin-film transistors with uniform electrical characteristics at high yield.


Association of Ureaplasma urealyticum biovars with clinical outcome for neonates, obstetric patients, and gynecological patients with pelvic inflammatory disease.
In this prospective study, the prevalence of the two Ureaplasma urealyticum biovars, parvo and T960, was determined in pregnant women and in gynecological patients colonized by ureaplasmas. Furthermore, we investigated the association of these biovars with gynecological complications and adverse pregnancy outcome. Isolates of U. urealyticum from 254 women were biotyped by a PCR method recently developed. The parvo biovar was found in 81% (206 of 254) of the patients, and the T960 biovar was found in 30% (76 of 254) of the patients; 6% (14 of 254) of the women were coinfected. Identical biovars were detected in mothers and their infants. Serial isolations or cultures from different sampling sites of the same individual revealed the same biovar. T960 was dominant in patients with pelvic inflammatory disease (57%) and patients who had had a miscarriage (42%), showed a higher rate of tetracycline resistance than did parvo isolates (55 versus 18%), and seemed to have more adverse effects on pregnancy outcome with regard to birth weight (2,500 versus 1,720 g), gestational age (35 versus 30 weeks), and preterm delivery (35 versus 77%).


Applicability of the Øie-Tozer model to predict three types of distribution volume (Vd) in humans: Vd in central compartment, Vd at steady state, and Vd at beta phase.
This study aimed to investigate the applicability of the Øie-Tozer model to predict human distribution volume (Vd) in the central compartment (V1 ), Vd at steady state (Vdss ), and Vd at beta phase (Vdβ ) based on animal Vd. Twenty compounds that have a human V1 /Vdss of 0.053-0.66 were selected from the literature. After intravenous administration of the compounds at 0.1 mg/kg to rats, dogs, and monkeys, plasma concentrations were determined, and pharmacokinetic parameters were obtained by one/two-compartmental analyses. The human V1 , Vdss , and Vdβ were predicted from animal Vd using the Øie-Tozer model, and the predictability was compared with that using proportionality and simple allometry. The Øie-Tozer model was the most reliable method for the overall prediction of Vd and applicable for accurately predicting human V1 , Vdss , and Vdβ (89%, 85%, and 68% of the compounds within a 3-fold error, respectively) when data of monkey for V1 and data of three animal species for Vdss and Vdβ were used. Additionally, the predicted human Vd with the two-compartment model was applicable for predicting pharmacokinetic profiles/parameters in humans after intravenous administration of 18 compounds [except for valproic acid (monophasic elimination profile) and chlorpromazine (deviation: Vdss < V1 )]. The prediction was more accurate than that using the predicted Vdss with the one-compartment model (e.g., underestimation of maximum plasma concentrations: 2 vs 8 compounds within a 3-fold error, respectively). In summary, the Øie-Tozer model was applicable for predicting human V1 , Vdss , and Vdβ , and their predicted Vd with the two-compartment model can lead to accurate pharmacokinetic prediction of compounds that show biphasic elimination.


The University of Ottawa Community Legal Clinic.
This is the third in a series of articles about legal clinics that provide specialized services to people with HIV/AIDS. In previous issues of the Newsletter, Ruth Carey provided an overview of the work of the HIV & AIDS Legal Clinic (Ontario) (HALCO), and Johanne Leroux described the work of the legal clinic of the Québec Committee for people with HIV in Montréal. In this article, Jennifer Duff, a low student and caseworker at the University of Ottawa Community Legal Clinic, describes the work of the HIV Legal Services division of the Ottawa Clinic.


Katkor cat litter, a non-invasive method of collecting cat urine for phosphate determination.
This study was done to compare the collection of cat urine, for phosphate concentration determination, by catheterisation with that via a proprietary cat litter (Katkor). The passage of urine through the litter or its retention in the litter for a period of 2 hours did not affect the concentration of phosphates compared with that of the original sample. Apart from a small volume of urine trapped in the litter by capillary action, and some urine adhering to the funnel in which the litter was placed, the litter proved to be an excellent medium for routine urine collection from cats, and more especially as an alternative to catheterisation when regular collection from a particular cat is required.


[Arterial reconstructive surgery of a coarctation of the abdominal aorta with involvement of renal and visceral arteries. Clinical and imagiologic evaluation 26 years after the operation].
The clinical case of a 13 years old female is reported, with the diagnosis of congenital coarctation of the abdominal aorta, with involvement of renal and visceral arteries, causing arterial hypertension and a systolic bruit in the auscultation of the epigastric and umbilical areas. Conventional angiography disclosed a stenotic process of the upper abdominal aorta, with concomitant ostial stenosis of the renal and digestive arteries, and post-stenotic dilatation of the celiac axis and superior mesenteric artery. The physical development of the patient, close to the adult pattern, allowed the performance of a complex revascularization procedure,accomplished in May 1984, consisting in the implantation of an aorto-aortic bypass graft, through the diaphragm, followed by visceral and renal revascularization, by means of independent prosthesis taken from the aortic bypass. The post-operative course was uneventful and blood pressure returned immediately to normal levels. Reviewed recently, the patient was found in good clinical condition,asymptomatic and with normal blood pressure, developing a normal family, social and Professional life. An Angio-CT evaluation, performed in February 2010, almost 26 years after the operation, revealed the complex revascularization procedure patent and working in excellent condition. To our knowledge, this seems to be the longest follow up of such a procedure employed successfully in a very rare clinical entity, thus justifying its presentation and divulgation.


Efficient two-step testing of gene-gene interactions in genome-wide association studies.
Exhaustive testing of all possible SNP pairs in a genome-wide association study (GWAS) generally yields low power to detect gene-gene (G × G) interactions because of small effect sizes and stringent requirements for multiple-testing correction. We introduce a new two-step procedure for testing G × G interactions in case-control GWAS to detect interacting single nucleotide polymorphisms (SNPs) regardless of their marginal effects. In an initial screening step, all SNP pairs are tested for gene-gene association in the combined sample of cases and controls. In the second step, the pairs that pass the screening are followed up with a traditional test for G × G interaction. We show that the two-step method is substantially more powerful to detect G × G interactions than the exhaustive testing approach. For example, with 2,000 cases and 2,000 controls, the two-step method can have more than 90% power to detect an interaction odds ratio of 2.0 compared to less than 50% power for the exhaustive testing approach. Moreover, we show that a hybrid two-step approach that combines our newly proposed two-step test and the two-step test that screens for marginal effects retains the best power properties of both. The two-step procedures we introduce have the potential to uncover genetic signals that have not been previously identified in an initial single-SNP GWAS. We demonstrate the computational feasibility of the two-step G × G procedure by performing a G × G scan in the asthma GWAS of the University of Southern California Children's Health Study.


When subjective experiences matter: power increases reliance on the ease of retrieval.
Past research on power focused exclusively on declarative knowledge and neglected the role of subjective experiences. Five studies tested the hypothesis that power increases reliance on the experienced ease or difficulty that accompanies thought generation. Across a variety of targets, such as attitudes, leisure-time satisfaction, and stereotyping, and with different operationalizations of power, including priming, trait dominance, and actual power in managerial contexts, power consistently increased reliance on the ease of retrieval. These effects remained 1 week later and were not mediated by mood, quality of the retrieved information, or number of counterarguments. These findings indicate that powerful individuals construe their judgments on the basis of momentary subjective experiences and do not necessarily rely on core attitudes or prior knowledge, such as stereotypes.