Absence of FcγRIII results in increased proinflammatory response in FcγRIII-KO cardiac recipients.
Alloantibody can contribute significantly to rejection of heart transplants by activation of complement and interactions with a variety of effector cells, including macrophages and monocytes through activating FcγRI, FcγRIII, FcγRIV, the inhibitory FcγRIIB and complement receptors. These receptors link cellular and humoral immunity by bridging the antibody specificity to effector cells. Activating FcγRs are also involved in serum amyloid P component (SAP)-mediated clearance of apoptotic bodies. B10.A (H-2a) hearts were transplanted into wild-type (WT) or FcγRIII-knockout (KO) C57BL/6 (H-2b) mouse recipients. Levels of alloantibodies and SAP in the circulation were determined by flow cytometry and enzyme-linked immunosorbent assay, respectively. Intragraft cytokine mRNA expression was measured by real-time polymerase chain reaction. Intragraft deposition of C4d, von Willebrand factor, SAP, and activated caspase 3 was visualized by immunochemistry. B10.A hearts in C57BL/6 FcγRIII-KO recipients were rejected acutely within 6 to 8 days compared with 10 to 14 days in WT. The rejection in FcγRIII-KO was accompanied by higher levels of circulating IgM/IgG alloantibodies and SAP than in WT recipients. Histology in FcγRIII-KO cardiac allograft recipients indicated perivascular margination of monocytes and neutrophils, vascular endothelial cell injury, and intense vasculocentric infiltrates with extensive apoptosis. Higher numbers of apoptotic cells, stronger C4d and SAP deposition, and extensive activated caspase 3 were found in areas of dense pockets of apoptotic blebs in FcγRIII-KO. We propose that absence of FcγRIII is associated with the lack of efficient SAP-mediated clearance of apoptotic cells through FcγRs. Apoptotic cells become immunogenic and induce enhanced inflammation, alloantibody production, and complement activation leading to accelerated cardiac allograft rejection.


Brain asymmetries in autism and developmental language disorder: a nested whole-brain analysis.
We report a whole-brain MRI morphometric survey of asymmetry in children with high-functioning autism and with developmental language disorder (DLD). Subjects included 46 boys of normal intelligence aged 5.7-11.3 years (16 autistic, 15 DLD, 15 controls). Imaging analysis included grey-white segmentation and cortical parcellation. Asymmetry was assessed at a series of nested levels. We found that asymmetries were masked with larger units of analysis but progressively more apparent with smaller units, and that within the cerebral cortex the differences were greatest in higher-order association cortex. The larger units of analysis, including the cerebral hemispheres, the major grey and white matter structures and the cortical lobes, showed no asymmetries in autism or DLD and few asymmetries in controls. However, at the level of cortical parcellation units, autism and DLD showed more asymmetry than controls. They had a greater aggregate volume of significantly asymmetrical cortical parcellation units (leftward plus rightward), as well as a substantially larger aggregate volume of right-asymmetrical cortex in DLD and autism than in controls; this rightward bias was more pronounced in autism than in DLD. DLD, but not autism, showed a small but significant loss of leftward asymmetry compared with controls. Right : left ratios were reversed, autism and DLD having twice as much right- as left-asymmetrical cortex, while the reverse was found in the control sample. Asymmetry differences between groups were most significant in the higher-order association areas. Autism and DLD were much more similar to each other in patterns of asymmetry throughout the cerebral cortex than either was to controls; this similarity suggests systematic and related alterations rather than random neural systems alterations. We review these findings in relation to previously reported volumetric features in these two samples of brains, including increased total brain and white matter volumes and lack of increase in the size of the corpus callosum. Larger brain volume has previously been associated with increased lateralization. The sizeable right-asymmetry increase reported here may be a consequence of early abnormal brain growth trajectories in these disorders, while higher-order association areas may be most vulnerable to connectivity abnormalities associated with white matter increases.


[Kinetics of conformational changes of methemoglobin complexed with liposomes].
Kinetics of methemoglobin structural changes in the complex with liposomes composed of phosphatidylcholine and its mixtures with cardiolipin has been studied. The amplitudes and rate constants of the two observed kinetic phases are determined. The fast kinetic phase is attributed to the formation of the unstable intermediate protein form, while the slow one is assumed to reflect dissociation of the heme--globin complex.


[Detection of N-acetyl-beta-D-hexosaminidase in urine].
A new modification was designed to determine the activity of N-acetyl-beta-D-hexosaminidase (NAH) in biological fluids. The properties of enzyme molecules to adsorb themselves on chitin at pH 4.5 were made use of within the case study. The mean NAH activity, in urine of virtually healthy children and adults, was shown to be equal, within a span time of 1 h, to 12.8 and 22.3 mumole of formed 4-nitrophenol/per 1 mmole of creatinine. The above mean NAH parameter was, in the amniotic fluid of pregnant women, 696 nmole of 4-nitrophenol/per 1 ml in 1 h. The NAH activity was studied in renal pathologies and in delayed intrauterine development of the fetus.


Cardiovascular disease and mortality after breast cancer in postmenopausal women: Results from the Women's Health Initiative.
Cardiovascular disease (CVD) is the leading cause of morbidity and mortality among older postmenopausal women. The impact of postmenopausal breast cancer on CVD for older women is uncertain. We hypothesized that older postmenopausal women with breast cancer would be at a higher risk of CVD than similar aged women without breast cancer and that CVD would be a major contributor to the subsequent morbidity and mortality. In a prospective Women's Health Initiative study, incident CVD events and total and cause-specific death rates were compared between postmenopausal women with (n = 4,340) and without (n = 97,576) incident invasive breast cancer over 10 years post-diagnosis, stratified by 3 age groups (50-59, 60-69, and 70-79). Postmenopausal women, regardless of breast cancer diagnosis, had similar and high levels of CVD risk factors (e.g., smoking and hypertension) at baseline prior to breast cancer, which were strong predictors of CVD and total mortality over time. CVD affected mostly women age 70-79 with localized breast cancer (79% of breast cancer cases in 70-79 age group): only 17% died from breast cancer and CVD was the leading cause of death (22%) over the average 10 years follow up. Compared to age-matched women without breast cancer, women age 70-79 at diagnosis of localized breast cancer had a similar multivariate-adjusted hazard ratio (HR) of 1.01 (95% confidence interval [CI]: 0.76-1.33) for coronary heart disease, a lower risk of composite CVD (HR = 0.84, 95% CI: 0.70-1.00), and a higher risk of total mortality (HR = 1.20, 95% CI: 1.04-1.39). CVD was a major contributor to mortality in women with localized breast cancer at age 70-79. Further studies are needed to evaluate both screening and treatment of localized breast cancer tailored to the specific health issues of older women.


Back to the future: museum specimens in population genetics.
Museums and other natural history collections (NHC) worldwide house millions of specimens. With the advent of molecular genetic approaches these collections have become the source of many fascinating population studies in conservation genetics that contrast historical with present-day genetic diversity. Recent developments in molecular genetics and genomics and the associated statistical tools have opened up the further possibility of studying evolutionary change directly. As we discuss here, we believe that NHC specimens provide a largely underutilized resource for such investigations. However, because DNA extracted from NHC samples is degraded, analyses of such samples are technically demanding and many potential pitfalls exist. Thus, we propose a set of guidelines that outline the steps necessary to begin genetic investigations using specimens from NHC.


A fibronectin matrix is required for differentiation of murine erythroleukemia cells into reticulocytes.
Erythroid differentiation of murine erythroleukemia (MEL) cells is far more extensive when the cells are attached to fibronectin-coated dishes than in suspension culture. Cells induced in suspension culture for 4 d become arrested at a late erythroblast stage and do not undergo enucleation. Incubation of cells in suspension beyond 4 d results in lysis. In contrast, cells induced by DMSO on fibronectin-coated dishes for 7 d differentiate into enucleating cells, reticulocytes, and erythrocytes. As determined by quantitative immunoblotting, cells induced in suspension culture accumulate approximately 33% of the amount of the major erythroid membrane protein Band 3 present in erythrocyte, whereas cells induced on fibronectin-coated dishes accumulate 80-100% of the amount present in erythrocytes. Both suspension-induced cells and cells induced on fibronectin-coated dishes accumulate approximately 90% of the amount of spectrin and ankyrin present in erythrocytes. As revealed by immunofluorescence microscopy during enucleation of MEL cells, both Band 3 and ankyrin are sequestered in the cytoplasmic fragment of the emerging reticulocyte. Enucleated and later-stage cells detach from the fibronectin matrix, due to the loss of the surface fibronectin receptor; this mimics the normal release of reticulocytes from the matrix of the bone marrow into the blood. Thus a fibronectin matrix provides a permissive microenvironment within which erythroid precursor cells reside, proliferate, migrate, and express their normal differentiation program.


Regulatory peptide metabolism at cell surfaces: the key role of endopeptidase-24.11.
This paper sets out to review some recent work on the role of endopeptidase-24.11. In renal brush borders, this enzyme is usually the only endopeptidase present among a host of exopeptidases, yet it appears to be the rate limiting step in the hydrolysis of a number of peptides, including bradykinin and the angiotensins. Endopeptidase-24.11 is widely, but not ubiquitously distributed--present not only in renal and intestinal brush borders, but also in lymph nodes, glandular tissues and the nervous system. All the last groups are rich in neuropeptides. The endopeptidase exhibits high specificity constants for a number of these potential substrates, including tachykinins, enkephalins and bradykinin. In the brain, immunocytochemical studies have shown colocalization of the enzyme and substance P. Thus, endopeptidase-24.11 has the appropriate topology, specificity, kinetic properties and localization to play a role in the metabolism of regulatory peptides.


Stability analysis of interval type-2 fuzzy-model-based control systems.
This paper presents the stability analysis of interval type-2 fuzzy-model-based (FMB) control systems. To investigate the system stability, an interval type-2 Takagi-Sugeno (T-S) fuzzy model, which can be regarded as a collection of a number of type-1 T-S fuzzy models, is proposed to represent the nonlinear plant subject to parameter uncertainties. With the lower and upper membership functions, the parameter uncertainties can be effectively captured. Based on the interval type-2 T-S fuzzy model, an interval type-2 fuzzy controller is proposed to close the feedback loop. To facilitate the stability analysis, the information of the footprint of uncertainty is used to develop some membership function conditions, which allow the introduction of slack matrices to handle the parameter uncertainties in the stability analysis. Stability conditions in terms of linear matrix inequalities are derived using a Lyapunov-based approach. Simulation examples are given to illustrate the effectiveness of the proposed interval type-2 FMB control approach.


DDX58(RIG-I)-related disease is associated with tissue-specific interferon pathway activation.
Singleton-Merten syndrome (SGMRT) is a rare immunogenetic disorder that variably features juvenile open-angle glaucoma (JOAG), psoriasiform skin rash, aortic calcifications and skeletal and dental dysplasia. Few families have been described and the genotypic and phenotypic spectrum is poorly defined, with variants in DDX58 (DExD/H-box helicase 58) being one of two identified causes, classified as SGMRT2. Families underwent deep systemic phenotyping and exome sequencing. Functional characterisation with in vitro luciferase assays and in vivo interferon signature using bulk and single cell RNA sequencing was performed. We have identified a novel DDX58 variant c.1529A>T p.(Glu510Val) that segregates with disease in two families with SGMRT2. Patients in these families have widely variable phenotypic features and different ethnic background, with some being severely affected by systemic features and others solely with glaucoma. JOAG was present in all individuals affected with the syndrome. Furthermore, detailed evaluation of skin rash in one patient revealed sparse inflammatory infiltrates in a unique distribution. Functional analysis showed that the DDX58 variant is a dominant gain-of-function activator of interferon pathways in the absence of exogenous RNA ligands. Single cell RNA sequencing of patient lesional skin revealed a cellular activation of interferon-stimulated gene expression in keratinocytes and fibroblasts but not in neighbouring healthy skin. These results expand the genotypic spectrum of DDX58-associated disease, provide the first detailed description of ocular and dermatological phenotypes, expand our understanding of the molecular pathogenesis of this condition and provide a platform for testing response to therapy.


Benefit of Adding Ezetimibe to Statin Therapy on Cardiovascular Outcomes and Safety in Patients With Versus Without Diabetes Mellitus: Results From IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial).
Ezetimibe, when added to simvastatin, reduces cardiovascular events after acute coronary syndrome. We explored outcomes stratified by diabetes mellitus (DM). In IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial), 18 144 patients after acute coronary syndrome with low-density lipoprotein cholesterol 50 to 125 mg/dL were randomized to 40 mg ezetimibe/simvastatin (E/S) or 40 mg placebo/simvastatin. The primary composite end point was cardiovascular death, major coronary events, and stroke. DM was a prespecified subgroup. The 4933 (27%) patients with DM were more often older and female, had had a prior myocardial infarction and revascularization, and presented more frequently with non-ST segment elevation acute coronary syndrome compared with patients without DM (each P<0.001). The median admission low-density lipoprotein cholesterol was lower among patients with DM (89 versus 97 mg/dL, P<0.001). E/S achieved a significantly lower median time-weighted average low-density lipoprotein cholesterol compared with placebo/simvastatin, irrespective of DM (DM: 49 versus 67 mg/dL; no DM: 55 versus 71 mg/dL; both P<0.001). In patients with DM, E/S reduced the 7-year Kaplan-Meier primary end point event rate by 5.5% absolute (hazard ratio, 0.85; 95% confidence interval, 0.78-0.94); in patients without DM, the absolute difference was 0.7% (hazard ratio, 0.98; 95% confidence interval, 0.91-1.04; Pint=0.02). The largest relative reductions in patients with DM were in myocardial infarction (24%) and ischemic stroke (39%). No differences in safety outcomes by treatment were present regardless of DM. When stratified further by age, patients ≥75 years of age had a 20% relative reduction in the primary end point regardless of DM (Pint=0.91), whereas patients <75 years of age with DM had greater benefit than those without (Pint=0.011). When stratified by the TIMI (Thrombolysis in Myocardial Infarction) Risk Score for Secondary Prevention, all patients with DM demonstrated benefit with E/S regardless of risk. In contrast, among patients without DM, those with a high risk score experienced a significant (18%) relative reduction in the composite of cardiovascular death, myocardial infarction, and ischemic stroke with E/S compared with placebo/simvastatin, whereas patients without DM at low or moderate risk demonstrated no benefit with the addition of ezetimibe to simvastatin (Pint =0.034). In IMPROVE-IT, the benefit of adding ezetimibe to statin was enhanced in patients with DM and in high-risk patients without DM. URL: https://www.clinicaltrials.gov. Unique identifier: NCT00202878.


Comparison of the Efficacy of Transthoracic Cannulation into the Ascending Aorta Versus Femoral Artery Cannulation in Minimally Invasive Cardiac Surgery.
To delineate the efficacy and safety of transthoracic cannulation to the ascending aorta through a right pleural cavity during minimally invasive cardiac surgery (MICS). We retrospectively assessed the records of 104 patients who underwent MICS in our institution between December 2011 and December 2018. Procedures included mitral valve repair (88 patients), aortic valve replacement (8 patients), atrial septal defect closure (6 patients), and myxoma resection (2 patients). Aortic valve replacements were performed through the third intercostal space (ICS), whereas the other procedures were mainly performed through the fourth ICS. The femoral group comprised 60 patients in whom an artificial graft was anastomosed to the femoral artery and 4 who underwent cannulation into the femoral artery. The aorta group comprised 40 patients in whom transthoracic cannulation was performed through the second or third ICS, separate from the main skin incision. No mortality or critical complications were associated with cardiopulmonary bypass. Perfusion pressure measured at outflow of the artificial lung (224 ± 43 vs. 190 ± 42; P < 0.001) and pump pressure measured at the outflow of the pump (293 ± 50 vs. 255 ± 57; P < 0.001) were significantly higher in the femoral group than in the aorta group. The skin incision lengths were similar (56.9 ± 6.9 vs. 55.1 ± 6.0 mm; P = 0.107). Transthoracic cannulation into the ascending aorta is reliable and can be safely performed. The possible risks associated with peripheral cannulation and retrograde perfusion can be avoided thereafter.


Fenofibrate Improves Liver Function and Reduces the Toxicity of the Bile Acid Pool in Patients With Primary Biliary Cholangitis and Primary Sclerosing Cholangitis Who Are Partial Responders to Ursodiol.
Cholestatic liver diseases result in the hepatic retention of bile acids, causing subsequent liver toxicity. Peroxisome proliferator-activated receptor alpha (PPARα) regulates bile acid metabolism. In this retrospective observational study, we assessed the effects of fenofibrate (a PPARα agonist) therapy on bile acid metabolism when given to patients with primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) who have had an incomplete response to Ursodiol monotherapy. When fenofibrate was added to Ursodiol therapy there was a significant reduction and in some cases normalization of serum alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase abnormalities, as well as pro-inflammatory cytokines. Combination fenofibrate treatment also reduced 7α-hydroxy-4-cholesten-3-one (C4), the bile acid precursor, as well as total, primary, and conjugated bile acids. In addition, principal components analysis and heatmap analysis show that bile acid metabolites trended closer to that of healthy control subjects. These favorable effects of fenofibrate on bile acid metabolism may contribute to its beneficial clinical effects in patients with PBC and PSC experiencing a subtherapeutic response to Ursodiol monotherapy.


[Gastric secretory function during enteral feeding].
Dogs with isolated Pavlovian pouches, a gastric fistula according to Basov, and a duodenal fistula were kept on enteral nutrition for 10 days. The nutritive mixture (35 kcal/kg bw) containing protein hydrolysates (2 g), fatty emulsion (2 g), and glucose solution with vitamins (2 g) was administered via a fistula to the intestine by drops daily for 8-9 h and gastric secretion was followed up. Enteral administration of the nutritive mixture stimulated gastric secretion whose intensity depended on the site and rate of its administration. The rate of juice secretion was the highest during administration to the duodenum. Less secretion was noticed during nutritive mixture supply to the jejunum. As the administration rate was raised, the secretion intensity increased. Gastric juice thus obtained was marked by high acidity and comparatively low pepsin concentration.


The degree of serum estradiol decline in early and midluteal phase had no adverse effect on IVF/ICSI outcome.
Estradiol levels fall rapidly in the luteal phase of ART cycles. So far, the effect of this estradiol decline on pregnancy outcome has remained controversial. To study the effect of early and midluteal estradiol decline on pregnancy and miscarriage rate. We also sought to determine whether estradiol fall was related to increased risk of bleeding per vagina in the first trimester among pregnancies which crossed 12 weeks. Tertiary Assisted conception center. Retrospective study. We analyzed data of 360 consecutive patients who underwent IVF-ET/ICSI cycles using one of the three protocols: Midluteal downregulation, short flare, and antagonist protocol. Statistical evaluation was performed with the Student's t test, Chi square, Fischer's exact test, analysis of variance, and Mann-Whitney tests were appropriate using SPSS for Windows, Standard version 11.0. The mean % EL-E2 and % ML-E2 declines were not significantly different in the pregnant and nonpregnant groups when analyzed separately in the three protocols. Also, the degree of midluteal estradiol decline did not correlate with pregnancy outcome. Moreover, the mean % early and midluteal estradiol decline did not differ significantly in patients with preclinical, clinical abortions, and ongoing pregnancy. The estradiol decline was not found to influence the risk of bleeding in the first trimester. Our results show that the degree of estradiol fall in the luteal phase of ART cycles does not influence pregnancy and first trimester miscarriage rate.


Altered Domain Functional Network Connectivity Strength and Randomness in Schizophrenia.
Functional connectivity is one of the most widely used tools for investigating brain changes due to schizophrenia. Previous studies have identified abnormal functional connectivity in schizophrenia patients at the resting state brain network level. This study tests the existence of functional connectivity effects at whole brain and domain levels. Domain level refers to the integration of data from several brain networks grouped by their functional relationship. Data integration provides more consistent and accurate information compared to an individual brain network. This work considers two domain level measures: functional connectivity strength and randomness. The first measure is simply an average of connectivities within the domain. The second measure assesses the unpredictability and lack of pattern of functional connectivity within the domain. Domains with less random connectivity have higher chance of exhibiting a biologically meaningful connectivity pattern. Consistent with prior observations, individuals with schizophrenia showed aberrant domain connectivity strength between subcortical, cerebellar, and sensorial brain areas. Compared to healthy volunteers, functional connectivity between cognitive and default mode domains showed less randomness, while connectivity between default mode-sensorial areas showed more randomness in schizophrenia patients. These differences in connectivity patterns suggest deleterious rewiring trade-offs among important brain networks.


Minimization of eddy power loss in the cryostat for a z-gradient array coil driven by an arbitrary pulse sequence: An electromagnetic approach.
This paper presents a novel computational approach to optimize gradient array performance for a given pulse sequence. Specifically, we propose an electromagnetic (EM) approach that minimizes eddy losses within the cryostat while maintaining key performance parameters such as field linearity, gradient strength, and imaging region's dimension and position. High-resolution EM simulations on the cryostat's surface are deployed to compute the net EM fields generated by each element of a gradient array coil at different frequencies. The computed fields are stored and combined for each frequency to form a quadratic vector-matrix-vector computation. The overall time-average eddy power loss within the cryostat assembly for arbitrary pulse sequences is computed using frequency domain superposition. The proposed approach estimates and regulates eddy power losses within the cryostat assembly. When compared to the stray field minimization approach, it can achieve over twice the reduction in eddy power loss. The proposed approach eliminates the need to sample the stray fields on the cryostat surface, which the number and position of the samples would be challenging when designing tunable array coils with capabilities that disrupt field symmetries. Additionally, the loss calculation considers the entire cryostat assembly rather than just the inner cylindrical surface of the warm shield. Our findings highlight the efficacy of an on-the-fly tuning method for the development of high-performance whole-body gradient array coils, effectively mitigating eddy losses within the cryostat and minimizing stray fields outside the coil assembly. This approach proves particularly advantageous for array coils with variable feeding currents.


Computed tomography analysis of acetabular anteversion and abduction.
The purpose of this study is to define the normal range of acetabular abduction and anteversion in relation to pelvic anatomy as depicted on conventional CT scan. We retrospectively reviewed 100 pelvic CT scans performed on patients presenting for evaluation of non-orthopaedic pathology. The study group consisted of 58 women and 42 men, aged between 18 and 88 years. Standard imaging protocol included an anteroposterior (AP) topogram with contiguous 5-mm thick axial images from the superior margin of the iliac crest to the lesser trochanter of the femur. The acetabular abduction was measured from the AP topogram by obtaining the angle between a line drawn from the acetabular teardrop to the lateral acetabular margin and a horizontal line between the ischial tuberosities. Acetabular anteversion was measured on axial images at the level of the mid-femoral head. We found the mean acetabular abduction to be 39 degrees (standard deviation 4 degrees, range 27 to 51 degrees) and the mean acetabular anteversion to be 23 degrees (standard deviation 5 degrees, range 12 to 39 degrees). Data suggests that acetabular anteversion may average 2.7 degrees lower in males than females and increase slightly with age, while abduction may tend to decrease with age. Ninety percent of patients had acetabular abduction between 31 and 46 degrees; the 90% central range for acetabular anteversion was estimated to be from 14 to 31 degrees. CT scanning is useful in accurately defining the normal range of acetabular abduction and antiversion. Knowledge of this normal anatomy will allow accurate assessment of acetabular component position as delineated on conventional CT scanning.


Assessing biodiversity loss due to land use with Life Cycle Assessment: are we there yet?
Ecosystems are under increasing pressure from human activities, with land use and land-use change at the forefront of the drivers that provoke global and regional biodiversity loss. The first step in addressing the challenge of how to reverse the negative outlook for the coming years starts with measuring environmental loss rates and assigning responsibilities. Pinpointing the global pressures on biodiversity is a task best addressed using holistic models such as Life Cycle Assessment (LCA). LCA is the leading method for calculating cradle-to-grave environmental impacts of products and services; it is actively promoted by many public policies, and integrated as part of environmental information systems within private companies. LCA already deals with the potential biodiversity impacts of land use, but there are significant obstacles to overcome before its models grasp the full reach of the phenomena involved. In this review, we discuss some pressing issues that need to be addressed. LCA mainly introduces biodiversity as an endpoint category modeled as a loss in species richness due to the conversion and use of land over time and space. The functional and population effects on biodiversity are mostly absent due to the emphasis on species accumulation with limited geographic and taxonomical reach. Current land-use modeling activities that use biodiversity indicators tend to oversimplify the real dynamics and complexity of the interactions of species among each other and with their habitats. To identify the main areas for improvement, we systematically reviewed LCA studies on land use that had findings related to global change and conservation ecology. We provide suggestion as to how to address some of the issues raised. Our overall objective was to encourage companies to monitor and take concrete steps to address the impacts of land use on biodiversity on a broader geographical scale and along increasingly globalized supply chains.


The serine protease TMPRSS6 is required to sense iron deficiency.
Hepcidin, a liver-derived protein that restricts enteric iron absorption, is the key regulator of body iron content. Several proteins induce expression of the hepcidin-encoding gene Hamp in response to infection or high levels of iron. However, mechanism(s) of Hamp suppression during iron depletion are poorly understood. We describe mask: a recessive, chemically induced mutant mouse phenotype, characterized by progressive loss of body (but not facial) hair and microcytic anemia. The mask phenotype results from reduced absorption of dietary iron caused by high levels of hepcidin and is due to a splicing defect in the transmembrane serine protease 6 gene Tmprss6. Overexpression of normal TMPRSS6 protein suppresses activation of the Hamp promoter, and the TMPRSS6 cytoplasmic domain mediates Hamp suppression via proximal promoter element(s). TMPRSS6 is an essential component of a pathway that detects iron deficiency and blocks Hamp transcription, permitting enhanced dietary iron absorption.


Cardiac artifact subspace identification and elimination in cognitive MEG data using time-delayed decorrelation.
To reduce physiological artifacts in magnetoencephalographic (MEG) and electroencephalographic recordings, a number of methods have been applied in the past such as principal component analysis, signal-space projection, regression using secondary information, and independent component analysis. This method has become popular as it does not have constraints such as orthogonality between artifact and signal or the need for a priori information. Applying the time-delayed decorrelation algorithm to raw data from a visual stimulation MEG experiment, we show that several of the independent components can be attributed to the cardiac artifact. Calculating an average cardiac activity shows that physiologically different excitation states of the heart produce similar field distributions in the MEG sensor system. This is equivalent to differing spectral properties of cardiac field distributions in the raw data. As a consequence, the algorithm combines, e.g., the R peak and the T wave of the cardiac cycle into a single component and the one-to-one assignment of each independent component with a physiological source is not justified in this case. To improve the signal quality of visually evoked fields, the multidimensional cardiac artifact subspace is suppressed from the data. To assess the preservation of the evoked signal after artifact suppression, a geometrical and a temporal measure are introduced. The suppression of cardiac and alpha wave artifacts allows, in our experimental setting, the reduction of the number of epochs to one half while preserving the visually evoked signal.


A polymicrobial perspective of pulmonary infections exposes an enigmatic pathogen in cystic fibrosis patients.
Lung disease is the leading cause of morbidity and mortality in cystic fibrosis (CF) patients. A modest number of bacterial pathogens have been correlated with pulmonary function decline; however, microbiological and molecular evidence suggests that CF airway infection is polymicrobial. To obtain a more complete assessment of the microbial community composition and dynamics, we undertook a longitudinal study by using culture-independent and microbiological approaches. In the process, we demonstrated that within complex and dynamic communities, the Streptococcus milleri group (SMG) can establish chronic pulmonary infections and at the onset of 39% of acute pulmonary exacerbations, SMG is the numerically dominant pathogen. We report the comprehensive polymicrobial community dynamics of a CF lung infection in a clinically relevant context. If a given organism, such as Pseudomonas aeruginosa, becomes resistant to antibiotic therapy, an alternative treatment avenue may mediate the desired clinical response by effectively managing the composition of the microbial community.


Nasal DNA methylation differentiates corticosteroid treatment response in pediatric asthma: A pilot study.
Treatment response to systemic corticosteroid in asthmatic children is heterogeneous and may be mediated by epigenetic mechanism(s). We aim to identify DNA methylation (DNAm) changes responsive to steroid, and DNAm biomarkers that distinguish treatment response. We followed 33 children (ages 5-18) presenting to the Emergency Department (ED) for asthma exacerbation. Based on whether they met discharge criteria in ≤24 hours, participants were grouped into good and poor responders to steroid treatment. Nasal samples were collected upon presentation to the ED (T0) and 18-24 hours later (T1). Genome-wide DNAm was measured for both time points in 20 subjects, and compared between T0 and T1 in good and poor responders respectively. DNAm at T1 was also compared between two responder groups. DNAm of selected CpGs was verified in the complete cohort, and expression of associated genes was examined. Interactions between DNAm, common single nucleotide polymorphism (SNP) located at the CpG sites and treatment responses were assessed. Three CpGs located in the OTX2 promoter showed responder-specific DNAm changes from T0 to T1, in which DNAm decreased in good but not in poor responders. Good and poor responders showed differential DNAm at T1 in 127 CpGs without and 182 CpGs with common SNP co-localization. Negative correlations between DNAm and gene expression were observed at CpGs located within the LDHC promoter, suggesting an impact of DNAm on gene regulation. Interactions between SNPs, DNAm and treatment response were detected. Acute systemic steroid treatment modifies nasal DNAm in good responders. Nasal DNAm, dependent or independent of SNPs, can differentiate response to treatment in acute asthmatic children.


Imaging evaluation of lower extremity infrainguinal disease: role of the noninvasive vascular laboratory, computed tomography angiography, and magnetic resonance angiography.
Peripheral arterial disease (PAD) is a manifestation of systemic atherosclerosis that commonly affects the lower extremities. The diagnosis of PAD and the subsequent treatment decisions rely on clinical exam and non-invasive imaging. The imaging modalities that aid in both diagnosis and treatment are the non-invasive vascular laboratory, computed tomography angiography (CTA) and magnetic resonance angiography (MRA). Each modality has its own advantages and limitations. Non-invasive vascular laboratory testing can be used as a good screening tool for PAD and is often used in conjunction with an additional imaging modality if necessary. CTA and MRA have similar advantages when compared to the "gold standard" of digital subtraction angiography. CTA utilizes ionizing radiation, however is readily available and cheaper when compared to MRA. CTA is attractive due to its 3-D reconstruction and multiplanar ability, but CTA can be limited in the presence of calcification. MRA also is attractive for its 3-D multiplanar imaging. It is important for a clinician to be familiar with the principles and technical aspects of each modality as it relates to lower extremity infrainguinal disease.


Bare market: campus sex ratios, romantic relationships, and sexual behavior.
Using a nationally representative sample of college women, we evaluate the effect of campus sex ratios on women's relationship attitudes and behaviors. Our results suggest that women on campuses where they comprise a higher proportion of the student body give more negative appraisals of campus men and relationships, go on fewer traditional dates, are less likely to have had a college boyfriend, and are more likely to be sexually active. These effects appear to stem both from decreased dyadic power among women on campuses where they are more numerous and from their increased difficulty locating a partner on such campuses.


Cognitive mechanisms of change in multidisciplinary treatment of patients with chronic widespread pain: a prospective cohort study.
To evaluate the contribution of improvement in negative emotional cognitions, active cognitive coping, and control and chronicity beliefs to the outcome of multidisciplinary treatment in patients with chronic widespread pain. Prospective cohort study. A total of 120 subjects diagnosed with chronic widespread pain, who completed a multidisciplinary pain programme. Data from baseline, 6 months and 18 months follow-up measurements were analysed. Longitudinal relationships were analysed between changes in cognitions and outcome, using generalized estimated equations. Outcome domains included: pain, interference of pain in daily life, depression, and global perceived effect. Cognitive domains included: negative emotional cognitions, active cognitive coping and control and chronicity beliefs. Improvements in negative emotional cognitions were associated with improvements in all outcome domains, in particular with improvement in interference of pain with daily life and depression (between baseline and 6 months, and 6 and 18 months). Improvements in active cognitive coping were associated with improvements in interference of pain in daily life (between baseline and 6 months). Improvements in control and chronicity beliefs were associated with improvements in pain and depression (between 6 and 18 months). Improvement in negative emotional cognitions seems to be a key mechanism of change in multidisciplinary treatment of chronic widespread pain. Improvement in active cognitive coping and improvement in control and chronic timeline beliefs may also constitute mechanisms of change, although the evidence is less strong.


Knowledge-Driven Mechanistic Enrichment of the Preeclampsia Ignorome.
Preeclampsia is a leading cause of maternal and fetal morbidity and mortality. Currently, the only definitive treatment of preeclampsia is delivery of the placenta, which is central to the pathogenesis of the disease. Transcriptional profiling of human placenta from pregnancies complicated by preeclampsia has been extensively performed to identify differentially expressed genes (DEGs). The decisions to investigate DEGs experimentally are biased by many factors, causing many DEGs to remain uninvestigated. A set of DEGs which are associated with a disease experimentally, but which have no known association to the disease in the literature are known as the ignorome. Preeclampsia has an extensive body of scientific literature, a large pool of DEG data, and only one definitive treatment. Tools facilitating knowledge-based analyses, which are capable of combining disparate data from many sources in order to suggest underlying mechanisms of action, may be a valuable resource to support discovery and improve our understanding of this disease. In this work we demonstrate how a biomedical knowledge graph (KG) can be used to identify novel preeclampsia molecular mechanisms. Existing open source biomedical resources and publicly available high-throughput transcriptional profiling data were used to identify and annotate the function of currently uninvestigated preeclampsia-associated DEGs. Experimentally investigated genes associated with preeclampsia were identified from PubMed abstracts using text-mining methodologies. The relative complement of the text-mined- and meta-analysis-derived lists were identified as the uninvestigated preeclampsia-associated DEGs (n=445), i.e., the preeclampsia ignorome. Using the KG to investigate relevant DEGs revealed 53 novel clinically relevant and biologically actionable mechanistic associations.


[Endoscopic interventions in tumors of the pineal area, posterior regions of the III ventricle, and the posterior cranial fossa].
The study was undertaken to develop and introduce low-invasive differential endoneurosurgical correction of spinal fluid circulatory disorders in tumors of the pineal area, posterior portions of the third ventricle and the posteranial fossa. The authors present their experience in surgically treating 12 patients by using endoscopy. Surgical techniques, endoscopic semiotics of tumors of the above site, metastases along the liquor pathways are described. The outcomes of this treatment are analyzed. An algorithm of surgical treatment is proposed. Certain advantages of endoscopic interventions over conventional treatments in the treatment of tumor-induced occlusive hydrocephalus justify their inclusion into a comprehensive examination and treatment of patients of this study group.


Dose perturbation due to the polysulfone cap surrounding a Fletcher-Williamson colpostat.
We conducted a metrological evaluation of the dosimetric impact due to the polysulfone cap used with the Fletcher-Williamson (FW) colpostat for 192Ir high-dose rate and pulsed-dose rate intracavitary brachytherapy using Monte Carlo simulations. Polysulfone caps with diameter of 30 mm, 25 mm, 20 mm, and 16 mm (mini-ovoid) were simulated and the absorbed dose rate in the surrounding water was calculated and compared to the dose rate for a bare 192Ir source in water. The dose perturbation depended on the cap diameter, distance away from the cap surface, and angular position around the cap. The largest dose rate reductions were found to be in the direction of the tumor bed where the cap is thickest. The range of perturbation over all depths and cap diameters was +2.8% (dose enhancement) to -6.8% (dose reduction). The FW colpostat cap's material composition should be modified to reduce this dosimetric effect or brachytherapy treatment planning dose algorithms should be improved to account for this perturbation.


Whole Exome Sequencing Among 26 Patients With Indeterminate Acute Liver Failure: A Pilot Study.
The etiology of acute liver failure (ALF) remains an important prognostic factor. The Acute Liver Failure Study Group recently reported that 150 of 2,718 adult patients with ALF (5.5%) had an indeterminate etiology. Our aim was to use whole exome sequencing to identify genetic variants associated with phenotypic, biochemical, and histologic features among patients with indeterminate ALF. This effort has defined a cohort of well-pedigreed patients with indeterminate ALF; DNA samples extracted from whole blood samples were obtained from 26 respective patients with indeterminate ALF. These samples were kept at the Acute Liver Failure Study Group repository at the NIDDK, Bethesda. Whole exome sequencing and bioinformatics analysis were performed at the Mayo Clinic Center of Individualized Medicine in Rochester, MN. Of the 26 patients, 8 survived spontaneously, 6 died, and 12 underwent a liver transplantation; all those transplanted were alive at 21 days after enrollment in the study. Twenty-two of the 26 patients presented as ALF. We found 12 variants associated with 11 genes. The most common variant was rs4940595 in the SERPINB11 gene which was found in 23 of the 26 patients. This variant had a stop codon; no reports of disorders have been associated with this variant. The next most commonly found variant was rs1135840 in the CYP2D6 gene; this mutation is a missense_variant and has been reported to be associated with hepatotoxicity of antituberculous therapy. None of our patients were receiving this therapy. We also found a significant asymmetric distribution of rs1800754 of the CYP2D7 gene and rs1135840 of the CYP2D6 gene between patients who survived spontaneously (75%) and those who died or underwent liver transplantation (30.5% and 25%, respectively). We found 12 variants of 11 genes significantly associated with ALF among adults with indeterminate etiology. We also found a significant asymmetric distribution of 2 variants belonging to the CYP2D7 and CYP2D6 genes, respectively, between those who survived spontaneously and those who died or underwent liver transplantation. The 2 most common variants, rs4940595 and rs1135840, of the SERPINB11 and CYP2D6 genes, respectively, found in our patients with ALF have been described as potentially important in the adaptive response combating the emergence of infectious diseases and associated with hepatotoxicity of antituberculous therapy, respectively. Our findings need to be expanded to include more patients with indeterminate ALF as well as viral, drug toxicity, and autoimmune etiologies to determine whether our findings are associated with the specific etiology, indeterminate, or with the overall ALF syndrome itself.


Dopaminergic neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in the mouse: an in vivo electrochemical study.
The long-term (i.e., 4-5 months) effects of large doses (3 X 50 mg/kg) of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on striatal dopamine-containing afferents were studied in the NMRI strain of mice. Recently improved in vivo electrochemical methods were first used to examine the magnitude, spatial distribution and temporal dynamics of monoamine release initiated via local application of potassium in various regions of the mouse striatum. Immunohistochemical localization of tyrosine hydroxylase and computer-based image analysis were also used to quantitate regional catecholamine-containing nerve fiber densities in the caudate nucleus. The in vivo electrochemical studies showed a statistically significant decrease in the average potassium-evoked release of electroactive species from the MPTP-treated mouse caudate nucleus vs. control. Greater decreases in release were seen in dorsal than in ventral striatum (55% vs. 33%). The average rise time of potassium-evoked release was also significantly prolonged (greater than 50%) after MPTP pretreatment. Histochemical studies showed an overall reduction in the density of dopamine-containing terminals in the drug-treated mice, with a greater loss observed in the more dorsal regions of the caudate nucleus. The experimental data thus support a long-term selective destruction of dorsal vs. ventral dopamine-containing afferents to the striatum by the neurotoxin MPTP in mice.


Cingulate fasciculus integrity disruption in schizophrenia: a magnetic resonance diffusion tensor imaging study.
Evidence suggests that a disruption in limbic system network integrity and, in particular, the cingulate gyrus (CG), may play a role in the pathophysiology of schizophrenia; however, the cingulum bundle (CB), the white matter tract furnishing both input and output to CG, and the most prominent white matter fiber tract in the limbic system, has not been evaluated in schizophrenia using the new technology of diffusion tensor imaging (DTI). We used line scan DTI to evaluate diffusion in the CB in 16 male schizophrenia patients and 18 male control subjects, group-matched for age, parental socioeconomic status, and handedness. We acquired 4-mm-thick coronal slices through the entire brain. Maps of fractional anisotropy (FA) were generated to quantify diffusion within the left and right CB on eight slices that included the central portion of the CB. Results showed group differences, bilaterally, in area and mean FA for CB, where patients showed smaller area and less anisotropy than controls. For patients, decreased left CB correlated significantly with attention and working memory measures as assessed by the Wisconsin Card Sorting Test. These data provide strong evidence for CB disruptions in schizophrenia, which may be related to disease-related attention and working memory abnormalities.


Vascular imaging with magnetic resonance and computed tomography.
Cross-sectional imaging of the cardiovascular system is successfully achieved with computed tomography (CT) and, more recently, magnetic resonance imaging (MRI). Limits of spatial resolution confine the routine application of either device to assessment of larger vessels, such as the aorta, vena cava, and renal veins. The decision to use one modality versus the other is frequently influenced by the clinical status of the patient, as well as the indication for diagnostic imaging. Some of the more common vascular abnormalities are depicted in this article, as imaged by these relatively new and expensive technologies. An explanation of the complex appearance of blood flow on MR is dependent on an understanding of some basic physical principles, such as flow-related enhancement and even-echo rephasing. MRI is presently more suitable than CT for the evaluation of medium-size vessels since the development of effective techniques for magnetic resonance angiography (MRA). Some of the important concepts, along with the terminology of this still-evolving field are presented. The quantification of blood flow by MRI is similarly an area of active research, and may ultimately supplant the existing methods.


[Heart growth in the human embryonic period (a study related to the 2d month of gestation)].
The growth of the heart was studied in 27 human staged embryos of post-somitic period (stages from 15 to 23, Carnegie Institution of Washington). The volume of the heart was determined multiplying the cardiac profiles areas (evaluated by point counting planimetry on serial sections) by the thickness of microtomy. Cardiac volume increase was examined relative to age, to crownrump length, and to body weight. The data were transformed into logarithms and bivariate relations were analysed according allometric equations of the form (log y = k log x + log b). The data were fitted according to three techniques: least squares, major axis, and reduced major axis. The slopes of the allometric regressions indicate positive allometry of the cardiac volume relative to embryonic age and to C-R length, and isometry relative to body weight.


Energy saving system with high effluent quality for municipal sewage treatment by UASB-DHS.
An up-flow anaerobic sludge blanket (UASB) - down-flow hanging sponge (DHS) was applied to Japanese municipal sewage treatment, and its treatability, energy consumption, and sludge production were evaluated. The designed sewage load was 50 m(3)/d. The sewage typically had a chemical oxygen demand (COD) of 402 mg/L, a suspended solids (SS) content of 167 mg/L, and a temperature of 17-29 °C. The UASB and DHS exhibited theoretical hydraulic retention times of 9.7 and 2.5 h, respectively. The entire system was operated without temperature control. Operation was started with mesophilic anaerobic digested sludge for the UASB and various sponge media for the DHS. Continuous operational data suggest that although the cellulose decomposition and methanogenic process in the UASB are temperature sensitive, stable operation can be obtained by maintaining a satisfactory sludge volume index and sludge concentration. For the DHS, the cube-type medium G3-2 offers superior filling rates, biological preservation and operational execution. The SS derived from the DHS contaminated the effluent but could be removed by optional sand filtration. A comparison with conventional activated sludge (CAS) treatment confirmed that this system is adequate for municipal sewage treatment, with an estimated energy requirement and excess sludge production approximately 75 and 85% less than those of CAS, respectively.


Inhibition of monoamine oxidase by substituted hydrazines.
1. The initial rate of inhibition of monoamine oxidase by phenethylhydrazine was shown to be similar, in pH-dependence and kinetic properties, to the oxidation of that compound by monoamine oxidase. 2. The time-course of irreversible inhibition of monoamine oxidase by phenethylhydrazine lags behind that of reversible inhibition. 3. Hydralzine was shown to be a reversible competitive inhibitor of monoamine oxidase, but phenylhydrazine is an irreversible inhibitor. Inhibition by the latter compound is not affected by the absence of oxygen, and the presence of substrate exerts no protective action. 4. Hydrazine does not inhibit monoamine oxidase unless a substrate and oxygen are present. 5. Phenethylidenehydrazine was found to be a time-dependent inhibitor of monoamine oxidase and the rate of inhibition was hindered by increasing oxygen concentration. 6. A mechanism for the inhibition of the enzyme by phenethylhydrazine is proposed in which the product of oxidation of this compound is a potent reversible inhibitor and an irreversible inhibitor of the enzyme. A computer simulation of such a mechanism predicts time-courses of inhibition that are in reasonable agreement with those observed experimentally.


Visual evoked potentials in infants exposed to methadone in utero.
We investigated the effects of maternal drug misuse on neonatal visual evoked potentials (VEPs). Flash VEPs were recorded within 4 days of birth from 21 term infants of mothers misusing drugs and prescribed substitute methadone and 20 controls. Waveforms were classified as typical, atypical, immature or non-detectable, and amplitude and latencies were measured. VEPs from drug-exposed infants were less likely to be of typical waveform and more likely to be immature or non-detectable (p<0.01) than those of control infants. They were also smaller in amplitude (median 10.8 vs 24.4 microV, p<0.001). VEPs of drug-exposed infants had matured after 1 week but remained of lower amplitude than VEPs of newborn controls (p<0.01) and were non-detectable in 15%. Flash VEPs differ between maternal drug-exposed and non-drug-exposed newborns. Future research should address the specific effects of maternal methadone and/or other illicit drug misuse on infant VEPs, and associations between neonatal VEPs and subsequent visual development.


Non-classical monocytes and its potential in diagnosing sepsis post cardiac surgery.
Sepsis is caused by a dysregulation of immune response to infection that results in very high mortality. Current laboratory tests and clinical criteria are inadequate to diagnose sepsis due to limited sensitivity and specificity. Circulating monocytes are important players in immune homeostasis and their altered HLA-DR expression indicate immune dysregulation. HLA-DR is an MHC Class II cell-surface receptor that can present foreign antigens to helper T cells and mount an inflammatory response. Therefore, we analyzed the variations in HLA-DR expression and the concentration of monocyte subsets for diagnosing post-surgical sepsis. In this double-blinded prospective cohort study, we adopted immunophenotyping and quantification of antigen expression by flowcytometry to detect the changes in circulating monocyte subsets in patients undergoing cardiac surgery. Statistical analysis was performed to identify significant changes and based on the predictive potential of measured variables ROC curve analysis was done. ROC curve permitted the choice of appropriate cut-off values using which a diagnostic protocol was developed. We observed that the monocyte subset concentrations in circulation varied differently after surgery. There was a significant downregulation of monocytic HLA-DR on both intermediate (p = 0.0477) and non-classical monocytes (p = 0.0333) at 48 h post-surgery. The monocyte subset analysis clearly showed that the patients with reduced pre-surgical non-classical monocyte count (p = 0.0430) coupled with post-surgical down-regulation of HLA-DR expression on the same subset had a higher incidence of developing sepsis after cardiac surgery. Here we are reporting for the first time, the significant influence of non-classical monocytes in inducing dysregulated host response and sepsis after cardiac surgery. Using multiple biomarkers associated with this monocyte subset, we established an algorithm for the diagnosis of sepsis at 48 h post cardiac surgery with 100% sensitivity and 69.23% specificity.


What Determines the Shape of an EQ-5D Index Distribution?
EQ-5D-3L index scores in patient and general populations typically have a nonnormal distribution, divided into 2 distinct groups. It is important to understand to what extent this is determined by the way that the EQ-5D-3L index is constructed rather than by the true distribution of ill health. This paper examines the determinants of the "2 groups" distribution pattern and the extent to which this pattern is attributable either to the EQ-5D-3L classification system used to create health state profiles or to the weights applied to profiles. Data from the English NHS PROMs program (hip and knee replacements and varicose vein and hernia repairs) and from a study of 2 chronic conditions (asthma and angina) were used to compare the distributions of EQ-5D-3L index scores with distributions from which weights have been stripped; profile data decomposed into their constituent dimensions and levels; a condition-specific index; and using weights from different countries, based on both time tradeoff and visual analogue scale. The EQ-5D-3L classification system generates differences between patients with the same condition in respect of dimensions that are mainly observed at level 2 or 3. The weights commonly used to calculate the index exacerbate this grouping by placing a larger weight on level 3 observations, generating a noticeable gap in index scores between the groups. Analyzing EQ-5D profile data enables a better understanding of the resulting distribution of EQ-5D scores. The distinctive shape observed for these distributions is the result of both the classification system and the weights applied to it.


Autoregulation of gastric blood flow and oxygen uptake.
The purpose of this study was to determine whether the ability of the stomach to autoregulate blood flow and oxygen uptake is altered by sympathetic denervation. Blood flow, oxygen extraction, local arterial pressure, and venous pressure were continuously monitored in sympathetically innervated and denervated autoperfused dog stomach preparations. As perfusion pressure was reduced in increments from 120 to 20 mmHg in innervated preparations, blood flow and oxygen uptake decreased while oxygen extraction and vascular resistance increased. Reductions in perfusion pressure in denervated preparations resulted in a decrease in blood flow, oxygen uptake, and vascular resistance, whereas oxygen extraction increased. The ability of the stomach to regulate blood flow and oxygen uptake was significantly improved after denervation, i.e., vascular resistance decreased and oxygen uptake remained relatively constant when arterial pressure was reduced. Oxygen uptake in denervated stomachs was generally higher than that in innervated stomachs. Autoregulation of gastric blood flow therefore appears to be improved by denervation. The better autoregulation observed after denervation may result either from a reduction in sympathetic tone and/or the increase in gastric oxygen demand.


Fetal loss associated with excess thyroid hormone exposure.
Maternal hypothyroidism and hyperthyroidism have deleterious effects on the outcome of pregnancy. While the effects of thyroid hormone (TH) deprivation on the fetus, independently from that on the mother, can be studied in infants with congenital hypothyroidism, this is not the case in those with fetal thyrotoxicosis. To study the effects of TH excess on fetuses carried by mothers with resistance to TH (RTH) who are euthyroid despite high TH levels but who may carry normal fetuses that are exposed to high maternal hormone levels. Retrospective study of 167 members of an Azorean family with RTH. Affected individuals had the RTH phenotype (high serum concentration of free thyroxine and triiodothyronine without suppressed thyrotropin) confirmed by genotyping to identify the Arg243-->Gln mutation in the TH receptor beta gene. Pregnancy outcome of affected mothers vs that of unaffected mothers carrying fetuses conceived by affected fathers, as well as that of unaffected first-degree relatives and outcomes from the general island population. Comparison of birth weights and blood concentrations of thyrotropin (TSH) obtained during routine neonatal screening of infants born to these 3 groups. Thirty-six couples with complete information belonged to 1 of 3 groups: affected mothers (n = 9), affected fathers (n = 9), and unaffected relatives (n = 18). Mean miscarriage rates were 22.9%, 2.0%, and 4.4%, respectively (chi2 = 8.66, P =.01). Affected mothers had an increased rate of miscarriage (z = 3.10, P =.002, by Wilcoxon rank-sum test). They had marginally higher than expected numbers of affected offspring, ie, 20 affected and 11 unaffected children (P =.07), while affected fathers had 15 affected and 12 unaffected children (P =.35). Unaffected infants born to affected mothers were significantly smaller than affected infants, having a mean SD score for gestational age of -1.79 (SD, 0.86) vs -0.06 (SD, 1.11) to -0.22 (SD, 0.70) for all other groups (P<.001). Only unaffected infants born to affected mothers had undetectable blood levels of TSH. There was a higher rate of miscarriage in mothers affected by RTH that may have involved predominantly unaffected fetuses. The lower birth weight and suppressed levels of TSH in unaffected infants born to affected mothers indicates that the high maternal TH levels produce fetal thyrotoxicosis. These data indicate a direct toxic effect of TH excess on the fetus.


Floristic survey of vascular plants of a poorly known area in the Brazilian Atlantic Forest (Flona do Rio Preto, Espírito Santo).
The Atlantic Forest is one of the most threatened biomes in the world. Despite that, this biome still includes many areas that are poorly known floristically, including several protected areas, such as the "Floresta Nacional do Rio Preto" ("Flona do Rio Preto"), located in the Brazilian State of Espírito Santo. This study used a published vascular plant species list for this protected area from the "Catálogo de Plantas das Unidades de Conservação do Brasil" as the basis to synthesise the species richness, endemism, conservation and new species occurrences found in the "Flona do Rio Preto". The published list of vascular plants was based on field expeditions conducted between 2018 and 2020 and data obtained from herbarium collections available in online databases. Overall, 722 species were documented for the "Flona do Rio Preto", 711 of which are native to Brazil and 349 are endemic to the Atlantic Forest. In addition, 60 species are geographically disjunct between the Atlantic and the Amazon Forests. Most of the documented species are woody and more than 50% of these are trees. Twenty-three species are threatened (CR, EN and VU), while five are Data Deficient (DD). Thirty-two species are new records for the State of Espírito Santo. Our results expand the knowledge of the flora of the Atlantic Forest and provide support for the development of new conservation policies for this protected area.


Role of radiofrequency ablation in the treatment of small hepatocellular carcinoma.
Radiofrequency ablation (RFA), one of the most advanced loco-regional ablative therapeutic methods, is widely utilized in the treatment of hepatocellular carcinoma (HCC). Because of its minimal invasiveness and high efficacy, RFA has been regarded as a curative therapy as alternative to surgical resection and liver transplantation. It brings new hope and a new treatment pattern for small HCC. In this article, we summarize the important role of RFA in the treatment of small HCC according to our clinical experience over six years. The prognosis of small HCC after RFA is comparable to that of surgical resection but with higher safety, less complications, wider applicability, and good long-term survival. RFA will play a more and more important role in the clinical treatment of small HCC.


Severe strongyloidiasis with negative serology after corticosteroid treatment.
Strongyloidiasis usually presents as a chronic and limited disease, but in some immunocompromised patients it may become a life-threatening disease. A 77-year-old Haitian male, with history of temporal arteritis on 40 mg of oral prednisone presented complaining of decreased oral intake, epigastric pain, and non-bloody diarrhea. He had bi-temporal wasting and a distended abdomen but without guarding or tenderness. Laboratory examination included mild leukocytosis, anemia, negative HIV antibody, negative parasite stool exam, and negative serology for Giardia and Strongyloides. CT of the abdomen showed multiple distended loops, without obstruction. During the admission he had a 4 g hemoglobin drop and a positive occult blood test, requiring blood transfusions, IV pantoprazole, and upper endoscopy. Findings included severe duodenitis, blunted villi, and intramucosal and luminal helminthic worms and eggs. Pathology showed Strongyloides stercoralis infection, confirmed by subsequent PCR. He was given 1 day of 15 mg oral ivermectin, diarrhea resolved, and was discharged with a percutaneous endoscopic gastrostomy tube because of the persistent lack of appetite. ConCLUSIONS: Given the persistent nature of strongyloidiasis and its high susceptibility to ivermectin, it potentially would be worth consider treating high-risk patients in the appropriate clinical and epidemiological setting, irrespective of screening test results, in order to avoid false-negative result consequences.


Deep anterior lamellar keratoplasty: indications, surgical techniques and complications.
The concept of lamellar keratoplasty (LK) is not new. However, it had been abandoned and largely replaced by the time-honored technique of penetrating keratoplasty (PK) because LK is technically demanding, time consuming and gives suboptimal visual outcomes due to interface irregularity arising from manual lamellar dissection. Recent improvements in surgical instruments and introduction of new techniques of maximum depth of corneal dissection as well as inherent advantages such as preservation of globe integrity and elimination of endothelial graft rejection have resulted in a re-introduction of LK as an acceptable alternative to conventional PK. This review article describes the indications, different techniques, clinical outcomes and complications of deep anterior LK.


Hierarchical sensory guidance of mauthner-mediated escape responses in goldfish (Carassius auratus) and cichlids (Haplochromis burtoni).
Acoustically-evoked escape behaviors were compared between goldfish (Carassius auratus), a hearing specialist, and the cichlid Haplochromis burtoni, a hearing nonspecialist. Fish were startled with compressive and rarefying, stimuli presented alone or together, and with compressive pulses preceded by a visual cue or after exposure to cobalt, an inhibitor of lateral line-innervated neuromast hair cells. These acoustic startle stimuli can evoke Mauthner neuron firing and are similar to but weaker than those produced by a largemouth bass (Micropterus salmoides) feeding on guppies. When sound stimuli were presented alone, both species avoided the direction of either the compressive or rarefying stimulus. If a light preceded and was contralateral to the compressive sound pulse, goldfish continued to avoid the sound source; cichlids avoided the visual cue and turned toward the sound. Goldfish performance improved significantly when the visual cue was in the same direction as the sound source. Goldfish performance also improved significantly after exposure to 0.1 mmol l-1 cobalt solution for 24 hours before testing, but cichlids would not startle after cobalt acclimation. A compressive pulse presented to one side of a fish simultaneously with a rarefying pulse on the other side causes the entire fish to accelerate with the water current. This strongly and directly accelerates the ear but tends to reduce both the pressure changes transduced by the swimbladder and activation of the mechanosensory lateral line. In this test, goldfish reliably avoided the compressive pulse. Cichlids, however, randomly avoided either speaker polarity but significantly avoided the speaker which had a faster onset. With more closely matched speakers, cichlids also preferentially avoided the compressive stimulus. Thus, the primitive sensory condition for auditory activation and guidance of Mauthner-neuron-initiated escape responses may have evolved to detect the initially compressive sounds associated with ram-type predators.


[Effect of allitridi on cAMP level of arterial wall and plasma of hypercholesterolemic rabbits].
30 New Zealand rabbits weighing 1.5-2.5 kg were all fed a common diet and subdivided into 3 groups. Group 1 (the control), group II received cholesterol (0.5 g/kg.d), while group III was added cholesterol (0.5 g/kg.d) and the allitridi (20 mg/kg.d). Blood cholesterol, cAMP and artery cAMP were determined by the usual technique. The results showed that serum cholesterol level was significantly reduced by allitridi during the 15 weeks period of study and the artery wall cAMP level of group I and group III were significantly higher than group II. But there was no significantly difference between group I and III. The difference of cAMP level in plasma was not significant.


Biological aspects of sharks caught off the Coast of Pernambuco, Northeast Brazil.
One hundred seventeen specimens of sharks were caught along the coast of Pernambuco State, Northern Brazil, between May 2004 and May 2007, among which 86 were blacknose sharks, Carcharhinus acronotus, enabling a more detailed study of the species. Blacknose sharks were caught in the 2 study areas along the Boa Viagem/Piedade and Paiva beaches, accounting for the highest relative abundance among the species caught (73.5% of total). Potentially dangerous sharks, tiger and bull sharks, were also caught in the same areas, whereas hammerhead and blacktip sharks were only captured off Boa Viagem/Piedade. Concerning the blacknose shark, the total length (TL) ranged from 39.0 to 180.0 cm. Among the 38 females analysed, 32 were juveniles, 11 were maturing, 2 were pre-ovulatory and 21 were pregnant. Sexing was possible for 75 of the 83 embryos, 38 of which were males and 37 were females, with a sex proportion of 1:0.9 and total length ranging between 6.4 and 63.5 cm. Ovarian fecundity ranged from 5 to 10 and uterine fecundity from 1 to 3, with an estimated gestational period of 9 months. Among the 48 males, 6 were juveniles and 42 were adults. Both males and females seem to reach sexual maturity at about 105.0 cm TL. Among the 86 stomachs analysed, only 22.1% had contents, with teleosts as the most frequent item.


Cultural perspectives on positive responses to extreme adversity: A playing field for metaphors.
In Euro-American societies, "resilience" and "post-traumatic growth" are commonly used metaphorical terms for positive responses to extreme adversity. However, research on illness narratives has demonstrated that other cultures may have different metaphorical concepts that act as vehicles for shared beliefs about how to overcome extreme adversity or traumatic experiences. The purpose of this article is to identify metaphors used in various cultures to describe positive responses to extreme adversity and to discuss the cultural ontologies and other socio-cultural factors that shape them. Metaphors of this nature were extracted from psychological, anthropological and ethnographic studies and were organized into categories: battle, path, container, balance, weight, object and network metaphors. Findings support the notion that metaphorical expressions related to positive responses to extreme adversity vary widely across cultures. We argue that an understanding of cultural differences in metaphors for mental health-related concepts is crucial to assisting trauma survivors from different cultural backgrounds.


Red blood cell transfusion practices: a College of American Pathologists Q-Probes study of compliance with audit criteria in 128 hospitals.
Most information on compliance with audit criteria for red blood cell (RBC) transfusions comes from single institutions; few studies have compared practices among many hospitals. To survey a cross-section of hospitals in 2008 for criteria and compliance with RBC transfusion guidelines, using the College of American Pathologists Q-Probes format. One hundred twenty-eight hospitals, representing about 4.5% (724,332 of 16,212,000) of all annual RBC usage in the United States, provided information on their RBC audit practices and their recent rates of compliance. They also each examined 50 RBC transfusion episodes for compliance with their guidelines. The participants' median, pretransfusion hemoglobin thresholds for audit review were 8.0 to 8.9 g/dL for most clinical settings and 9.0 to 9.9 g/dL for patients with underlying cardiopulmonary disease. For the transfusion episodes examined, 60% (2063 of 6518) were for a single unit. The median of the institutional averages for pretransfusion hemoglobin was 8.1 g/dL, and the median rate of compliance was 69% (range, 0%-100%). Involvement by a pathologist or transfusion medicine expert in the audit system was associated with more-strict audit criteria and better compliance. Median hemoglobin thresholds for RBC transfusion audits were somewhat higher than currently evolving recommendations, but opportunities for improvement were provided by expert involvement and by the growing frequency of 1-unit transfusions.


Different approaches of symbolic dynamics to quantify heart rate complexity.
The analysis of symbolic dynamics applied to physiological time series is able to retrieve information about dynamical properties of the underlying system that cannot be gained with standard methods like e.g. spectral analysis. Different approaches for the transformation of the original time series to the symbolic time series have been proposed. Yet the differences between the approaches are unknown. In this study three different transformation methods are investigated: (1) symbolization according to the deviation from the average time series, (2) symbolization according to several equidistant levels between the minimum and maximum of the time series, (3) binary symbolization of the first derivative of the time series. Each method was applied to the cardiac interbeat interval series RR(i) and its difference ΔRR(I) of 17 healthy subjects obtained during head-up tilt testing. The symbolic dynamics of each method is analyzed by means of the occurrence of short sequences ('words') of length 3. The occurrence of words is grouped according to words without variations of the symbols (0V%), words with one variation (1V%), two like variations (2LV%) and two unlike variations (2UV%). Linear regression analysis showed that for method 1 0V%, 1V%, 2LV% and 2UV% changed with increasing tilt angle. For method 2 0V%, 2LV% and 2UV% changed with increasing tilt angle and method 3 showed changes for 0V% and 1V%. In conclusion, all methods are capable of reflecting changes of the cardiac autonomic nervous system during head-up tilt. All methods show that even the analysis of very short symbolic sequences is capable of tracking changes of the cardiac autonomic regulation during head-up tilt testing.


Calcium ionophore A-23187 and 12-O-tetradecanoyl-phorbol-13-acetate stimulation of prostaglandin synthesis in herpes simplex virus type 2-transformed rat cells.
The purpose of this investigation was to determine whether cells transformed by herpes simplex virus type 2 (HSV-2) can be stimulated to synthesize prostaglandins (PG). Stimulation was determined by measuring the release of PG into overlay fluids from cell monolayers prelabeled with [3H]arachidonic acid. Results showed that Ca2+ ionophore A-23187 markedly stimulated arachidonic acid release starting 30 min after treatment of HSV-2-transformed and nontransformed rat embryo fibroblast cells. However, only HSV-2-transformed cells were stimulated in production of PG. HSV-2-transformed, nontumorigenic, rat embryo fibroblast, line G, clone 2.0 cells synthesize nearly equal amounts of prostaglandin E2 (PGE2) and prostaglandin F2 alpha, while tumor (rat fibrosarcoma) cells synthesize primarily PGE2. Stimulation of PGE2 synthesis by Ca2+ ionophore A-23187 or 12-O-tetradecanoyl-phorbol-13-acetate decreased as rat fibrosarcoma cells were serially passaged in tissue culture. At low passage of parental rat fibrosarcoma cells, four distinct morphological clonal cell lines were isolated, which varied markedly in their capacity to be stimulated in PG synthesis by 12-O-tetradecanoyl-phorbol-13-acetate. There was correlation between the capacity of clone 1 cells to be stimulated in PGE2 synthesis by serum alone and capacity of the tumors produced by the clone 1 cells to metastasize to the lungs of syngeneic tumor-bearing rats. In summary, cell transformation by HSV-2 appears to be essential for stimulation of PG synthesis in cells. The capacity to be stimulated in arachidonic acid metabolism and PG synthesis may be important in the process of carcinogenesis by a putative human cancer virus.


Early Miocene origin and cryptic diversification of South American salamanders.
The currently recognized species richness of South American salamanders is surprisingly low compared to North and Central America. In part, this low richness may be due to the salamanders being a recent arrival to South America. Additionally, the number of South American salamander species may be underestimated because of cryptic diversity. The aims of our present study were to infer evolutionary relationships, lineage diversity, and timing of divergence of the South American Bolitoglossa using mitochondrial and nuclear sequence data from specimens primarily from localities in the Andes and upper Amazon Basin. We also estimated time of colonization of South America to test whether it is consistent with arrival via the Panamanian Isthmus, or land bridge connection, at its traditionally assumed age of 3 million years. Divergence time estimates suggest that Bolitoglossa arrived in South America from Central America by at least the Early Miocene, ca. 23.6 MYA (95% HPD 15.9-30.3 MYA), and subsequently diversified. South American salamanders of the genus Bolitoglossa show strong phylogeographic structure at fine geographic scales and deep divergences at the mitochondrial gene cytochrome b (Cytb) and high diversity at the nuclear recombination activating gene-1 (Rag1). Species often contain multiple genetically divergent lineages that are occasionally geographically overlapping. Single specimens from two southeastern localities in Ecuador are sister to the equatoriana-peruviana clade and genetically distinct from all other species investigated to date. Another single exemplar from the Andes of northwestern Ecuador is highly divergent from all other specimens and is sister to all newly studied samples. Nevertheless, all sampled species of South American Bolitoglossa are members of a single clade that is one of several constituting the subgenus Eladinea, one of seven subgenera in this large genus. The ancestors of South American salamanders likely arrived at least by the Early Miocene, well before the completion of the Late Pliocene Panamanian land bridge (widely accepted as ca. 3 MYA). This date is in agreement with recent, controversial, arguments that an older, perhaps short-lived, land connection may have existed between South America and present-day Panama 23-25 MYA. Since its arrival in South America, Bolitoglossa has diversified more extensively than previously presumed and currently includes several cryptic species within a relatively small geographic area. Rather than two upper Amazonian species currently recorded for this region, we propose that at least eight should be recognized, although these additional lineages remain to be formally described.


Socio-cultural factors that foster use and abuse of alcohol among a sample of enlisted personnel at four Navy and Marine Corps installations.
Rates of heavy drinking are consistently higher among U.S. military personnel than among civilians, particularly among young male personnel. In addressing drinking in the military, more information is needed on contextual factors influencing drinking to better understand the conditions that lead to or facilitate drinking. Results from 15 focus groups conducted with enlisted personnel at 2 Navy and 2 Marine Corps installations as part of formative research for an alcohol abuse prevention trial are reported in this article. The study explored the "drinking climate" of each installation in terms of shared attitudes and recognized norms regarding alcohol use and installation personnel's general understanding of policies concerning alcohol consumption. Analysis revealed several contextual factors that add to our understanding of drinking behaviors.


Effect of phosphate deprivation on phosphate reabsorption in rat nephron: role of PTH.
The sites of enhanced phosphate (PO4) reabsorption after PO4 deprivation were investigated before and after infusion of parathyroid hormone (PTH) in acutely thyroparathyroidectomized rats. Animals were fed either a control PO4 diet (1.6% P) or a low PO4 diet (0.025% P) for 2 days or 7-10 days. In control rats, PTH decreased PO4 reabsorption in the proximal tubule, loop of Henle, and distal convolution. PO4 reabsorption in the proximal tubule was enhanced after 2 days of PO4 deprivation. In this group, proximal PO4 reabsorption was decreased by PTH but remained greater than in control rats (70 +/- 6 vs. 45 +/- 6 pmol/min; P less than 0.025). After PTH, PO4 reabsorption increased in the loop of Henle from 3 +/- 0.5 to 13 +/- 2 pmol/min (P less than 0.005), whereas it was unaltered in the distal convolution in PO4-deprived rats. PTH markedly increased fractional excretion of PO4 in control rats but not in PO4-deprived rats. After prolonged PO4 deprivation, PO4 reabsorption along the nephron was unaltered by PTH. These results demonstrate that acute PO4 deprivation enhances PO4 reabsorption in the proximal tubule, although the phosphaturic effect of PTH in this segment is not abolished. Resistance to the inhibitory effect of PTH on PO4 reabsorption in some portion of the loop of Henle and possibly also in the distal convolution accounts for the absence of a significant phosphaturic effect of the hormone in acutely PO4-deprived rats. Prolongation of PO4 deprivation results in unresponsiveness to PTH extending to the proximal tubule.


Can child restraint product information developed using consumer testing sustain correct use 6 months after child restraint purchase? Study protocol for a cluster randomised controlled trial.
With long-standing and widespread high rates of errors in child restraint use, there is a need to identify effective methods to address this problem. Information supplied with products at the point of sale may be a potentially efficient delivery point for such a countermeasure. The aim of this study is to establish whether product materials developed using a consumer-driven approach reduce errors in restraint use among purchasers of new child restraint systems. A cluster randomised controlled trial (cRCT) will be conducted. Retail stores (n=22) in the greater Sydney area will be randomised into intervention sites (n=11) and control sites (n=11), stratified by geographical and socioeconomic indicators. Participants (n=836) will enter the study on purchase of a restraint. Outcome measures are errors in installation of the restraint as observed by a trained researcher during a 6-month follow-up home assessment, and adjustment checks made by the parent when the child is placed into the restraint (observed using naturalistic methods). Process evaluation measures will also be collected during the home visit. An intention-to-treat approach will be used for all analyses. Correct use and adjustment checks made by the parent will be compared between control and intervention groups using a logistic regression model. The number of installation errors between groups will be compared using Poisson regression. This cRCT will determine the effectiveness of targeted, consumer-driven information on actual error rates in use of restraints. More broadly, it may provide a best practice model for developing safety product information. ACTRN12617001252303p; Pre-results.


Low-dose terlipressin during long-term hyperdynamic porcine endotoxemia: effects on hepatosplanchnic perfusion, oxygen exchange, and metabolism.
To investigate whether the vasopressin analog terlipressin might induce hepatosplanchnic ischemia during long-term, hyperdynamic, volume-resuscitated porcine endotoxemia. Prospective, randomized, controlled experimental study with repeated measures. Investigational animal laboratory. Eighteen pigs were divided into two groups receiving either endotoxin alone (control group, n = 10) or endotoxin and terlipressin (n = 8). Pigs were anesthetized, mechanically ventilated, and instrumented and received a continuous intravenous infusion of Escherichia coli endotoxin. Animals were resuscitated with hydroxyethyl starch targeted to maintain mean arterial pressure >60 mm Hg. Twelve hours after the start of the endotoxin infusion, terlipressin (5-15 microg.kg.hr titrated to maintain mean arterial pressure at preendotoxin levels) or its vehicle was administered for 12 hrs. Terlipressin increased mean arterial pressure and systemic vascular resistances, which was affiliated with a decrease in cardiac output and global oxygen consumption. Terlipressin restored the hepatic artery buffer response, which led to an increase in hepatic artery flow, ultimately resulting in well-maintained liver oxygen delivery, oxygen uptake, and all other variables of regional metabolism and organ function. Terlipressin markedly attenuated the hepatosplanchnic venous acidosis but was associated with pronounced hyperlactatemia. During long-term hyperdynamic porcine endotoxemia, the well-known vasoconstrictor properties of terlipressin blunted the progressive decrease in mean arterial pressure without any detrimental effect on hepatosplanchnic perfusion, oxygen exchange, and metabolism. The marked terlipressin-induced hyperlactatemia did not originate from the hepatosplanchnic organs but from extrasplanchnic tissues, possibly muscle and skin.


Factors contributing to regular smoking in adolescents in Turkey.
The objectives of this study were to determine the levels of lifetime cigarette use, daily use, and current use among young people (aged 15-19 years) and to examine the risk factors contributing to regular smoking. The number of students was determined proportionately to the numbers of students in all the high schools in the province of Trabzon in Turkey. The data were gathered using the questionnaire method. A total of 4666 students participated in the study. The chi-square test and logistic regression analysis were used in data analysis. Of the 4666 students who took part in the study, the level of lifetime cigarette use was 38.2% (n = 1796), that of lifetime daily cigarette use was 10.5% (n = 491), and that of current cigarette use was 9.5% (n = 447). Male students (P < .0005), those whose mothers were smokers (P < .0005), those whose fathers smoked (P = .005), those whose siblings smoked (P<.0005), those whose friends smoked (P < .0005), those whose teachers smoked (P = .001), and low achievers in school (P < .0005) stated that they significantly smoked on a more regular basis. According to the results of the logistic regression analysis, the following risk factors were statistically significant: male students smoked 3.02 times (95% CI 2.20-4.16) more than females, those whose mothers were smokers smoked 1.57 times (95% CI 1.09-2.28) more than those whose mothers were not, those whose friends were smokers smoked 2.42 times (95% CI 1.73-3.39) more than those whose friends were non-smokers, poor achievers in school smoked 2.62 times (95% CI 1.97-3.49) more than high achievers, and those without poor grades smoked 1.75 times more (95% CI 1.23-2.40), the risk rising 1.06 times (95% CI 1.01-1.11) with earlier age at first experimentation. The risk of daily cigarette use was observed to decline by 0.91 times (95% CI 0.84-0.98) with increasing numbers of siblings. Effective smoking prevention programs should take into account the dominant influence of peer groups in the onset and continuation of smoking.


Initial psychological response to parental death.
A cohort of patients seeking help at a clinical research center providing time-limited brief therapy for posttraumatic stress disorders was assembled. The single life event experienced by each was death of a parent. A nonequivalent comparison group was gathered by review of hospital death records. Both groups received the same type of evaluation interview and completed the same measures, which were similar to those done for both groups by the clinical interviewer. These data indicated that while both groups contained persons with medium to high distress levels, the patient group was most uniformly composed of such persons; when compared with the field-study group, the patient group had significant and important elevations of distress levels.


Bypassing the emergency room to reduce door-to-balloon time and improve outcomes of patients with ST elevation myocardial infarction: the Acute Coronary Syndrome Israeli Survey experience.
Rapid reperfusion of an infarct-related artery is crucial for the successful treatment of ST elevation myocardial infarction. Every effort should be made to shorten door-to-balloon time. To investigate whether bypassing the emergency room (ER) has a positive influence on door-to-balloon time in patients presenting with ST elevation myocardial infarction (STEMI) and whether the reduction in door-to-balloon time improves patients' clinical outcome. We analyzed data of 776 patients with STEMI from the 2004 and the 2006 Acute Coronary Syndrome Israeli Survey (ACSIS) registry. The ACSIS is a biennial survey on acute myocardial infarction performed in all 25 intensive cardiac care units in Israel during a 2-month period. Twenty-five percent of patients (193 of 776) arrived directly to the intensive cardiac care unit (ICCU) and 75% (583 of 776) were assessed first in the ER. We compared door-to-balloon time, ejection fraction, 30 days MACE (major adverse cardiac and cerebrovascular events) and 30 days mortality in the two study groups. There was significantly shorter door-to-balloon time in the direct ICCU group as compared with the ER group (45 vs. 79 minutes, P< 0.002). Patients in the direct ICCU group were more likely to have door-to-balloon time of less than 90 minutes in accordance with ACC/AHA guidelines (88.7% vs. 59.2%, P < 0.0001). Moreover, patients in the direct ICCU group were less likely to have left ventricular ejection fraction < 30% (5.4% vs. 12.2%, P= 0.045) and less likely to have symptoms of overt congestive heart failure. Lastly, 30 days MACE was significantly lower in the direct ICCU group (22 vs. 30%, P< 0.004). There is significant reduction of the door-to-balloon time in the direct ICCU admission strategy. This reduction translates into improvement in clinical outcome of patients. It is reasonable to apply the direct ICCU strategy to patients with STEMI.


Removal of heavy metals through adsorption using sand.
The removal of four heavy metals i.e. Pb, Cr, Cu, and Zn from their aqueous solutions, using ordinary sand as an adsorbent, was studied at 20 degrees C. The amount of metal adsorbed to form monolayer on sand (a(m)), obtained from Langmuir isotherm, exhibited the preference of metals for sand in the order Pb > Cr > Cu > Zn. The heavy metal-sand adsorption phenomena can be illustrated on the basis of the interaction between surface functional group of silicates (sand) and the metal ions. It is deduced that sand can be used as a low cost adsorbent for the removal of heavy metal from wastewater (containing low conc. of metals), especially in the developing countries.


The compliance of the community and private pharmacies' patients.
This issue is an attempt to expose the extent of compliance, respectively of non-compliance among the patients of the community and private pharmacies in Sofia. The authors make an attempt to elucidate the factors that influence upon the non-compliance of the patients in order to increase the rate of compliance among them. The results of the analysis of the received data show that the level of the compliance is 69% among the studied patients. Despite the presented adequate level of compliance among the patients, there are possibilities for the individualisation of the treatment, for supply with more information and for improvement of the patient-physician and patient-pharmacist interrelations.


Substituent effects on the gas-phase fragmentation reactions of sulfonium ion containing peptides.
The multistage mass spectrometric (MS/MS and MS3) gas-phase fragmentation reactions of methionine side-chain sulfonium ion containing peptides formed by reaction with a series of para-substituted phenacyl bromide (XBr where X=CH2COC6H4R, and R=--COOH, --COOCH3, --H, --CH3 and --CH2CH3) alkylating reagents have been examined in a linear quadrupole ion trap mass spectrometer. MS/MS of the singly (M+) and multiply ([M++nH](n+1)+) charged precursor ions results in exclusive dissociation at the fixed charge containing side chain, independently of the amino acid composition and precursor ion charge state (i.e., proton mobility). However, loss of the methylphenacyl sulfide side-chain fragment as a neutral versus charged (protonated) species was observed to be highly dependent on the proton mobility of the precursor ion, and the identity of the phenacyl group para-substituent. Molecular orbital calculations were performed at the B3LYP/6-31+G** level of theory to calculate the theoretical proton affinities of the neutral side-chain fragments. The log of the ratio of neutral versus protonated side-chain fragment losses from the derivatized side chain were found to exhibit a linear dependence on the proton affinity of the side-chain fragmentation product, as well as the proton affinities of the peptide product ions. Finally, MS3 dissociation of the nominally identical neutral and protonated loss product ions formed by MS/MS of the [M++H]2+ and [M++2H]3+ precursor ions, respectively, from the peptide GAILM(X)GAILK revealed significant differences in the abundances of the resultant product ions. These results suggest that the protonated peptide product ions formed by gas-phase fragmentation of sulfonium ion containing precursors in an ion trap mass spectrometer do not necessarily undergo intramolecular proton 'scrambling' prior to their further dissociation, in contrast to that previously demonstrated for peptide ions introduced by external ionization sources.


Volume expansion predominantly inhibits proximal reabsorption of NaCl rather than NaHCO3.
The present study quantitated the effect of extracellular volume expansion on absolute proximal bicarbonate, chloride, and water reabsorption in 10 Sprague-Dawley rats. Paired free-flow micropuncture measurements were made in the plasma-replete euvolemic state and following 10% body wt isohydric, colloid-free volume expansion. Single nephron glomerular filtration rate and glomerular ultrafiltrate concentration of bicarbonate and chloride were similar in the two conditions. Volume expansion caused absolute proximal reabsorption of bicarbonate to fall by only 7% (from 987 +/- 39 to 920 +/- 53 pmol/min, P less than 0.05). This decrement in bicarbonate reabsorption was compatible with the known increase in bicarbonate permeability and backleak induced by expansion. In contrast, a marked 26% fall in absolute proximal chloride reabsorption occurred (from 1,601 +/- 147 to 1,180 +/- 149 peq/min, P less than 0.005), attributed to alteration in transcellular rather than passive sodium chloride transport. Thus, the decrease in absolute proximal volume reabsorption (from 19.7 +/- 1.0 to 16.7 +/- 1.2 nl/min, P less than 0.005) induced by volume expansion was predominantly a consequence of inhibition of sodium chloride rather than sodium bicarbonate reabsorption.


Future directions. Augmentation of osteoporotic vertebral bodies.
Because current medical and surgical treatments of vertebral body fractures are less than adequate, there is a need for interventions that decrease the likelihood of occurrence of these fractures and improve the treatment options once they have occurred. One such broad category of intervention involves the fortification or augmentation of the vertebral bodies. In addition to prophylactically stabilizing osteoporotic vertebral bodies at risk for fracture, augmentation of vertebral bodies that have already fractured may prove to be useful by reducing pain, improving function, and preventing further collapse and deformity. Vertebral body augmentation can also be used as an adjunct to fixation of internal hardware--for example, pedicle screws-in osteoporotic spines. A number of products are now available or are in clinical trials. The most promising products are injectable materials-polymethylmethacrylate or mineral bone cement. The early clinical results using polymethylmethacrylate in percutaneous vertebroplasty for fractured vertebral bodies and the results in vitro using an injectable mineral cement for vertebral body fortification are encouraging. Although the principle of vertebral body augmentation remains encouraging, data to support the widespread use of these techniques remain sparse, and the indications for their use should be more clearly defined.