Malaria sporozoites leave behind trails of circumsporozoite protein during gliding motility.
As Plasmodium sporozoites undergo gliding motility in vitro, they leave behind trails of circumsporozoite (CS) protein that correspond to their patterns of movement. This light microscopic observation was made using Plasmodium berghei sporozoites, a monoclonal antibody (MAb H4) directed against the immunodominant repetitive epitope of the CS protein of P. berghei, and an immunogold-silver staining (IGSS) technique. Sporozoites pretreated with agents that inhibit sporozoite motility and invasiveness did not produce trails. Sporozoites that glided on microscope slides coated with MAb H4 left behind considerably longer CS protein trails than those on uncoated slides, and the staining of these trails was more intense. The fact that the CS protein is an exoantigen continuously released as trails by motile sporozoites, together with our previous finding that anti-CS protein antibodies inhibit sporozoite motility, strongly suggests that the CS protein plays a role in gliding motility. The sensitive IGSS technique used in this study may be a useful tool in the study of the translocation of surface proteins during gliding of other apicomplexans, other protists, and bacteria.


[The surgical treatment of the pleural empyem].
The treatment results of the 286 patients with pleural empyem after thoracic injuries (n=107) and closed trauma of the pleural cavity (n=179) were retrospectively analyzed. The frequency of pleural empyem was 1.39% by injuries and 1.34% by the closed thoracic trauma. 15 (14%) patients of the first group developed the bronchopleural fistula, whereas the complication was observed in 32 (17.9%) patients of the second group. The adequate pleural drainage with intrapleural enzyme therapy in acute inflammation period allowed recovery in 78% and 71.9% of patients, respectively. Early videothoracoscopic sanation of the pleural cavity shortened the recovery time in more then 1.5 times. The chronization of the empyem was more often observed after the closed thoracic trauma - 14.5% rather than 6.5% after the open thoracic injury. The lethality rate by pleural empyem was 14% after the open injuries and 15.6% after the closed trauma.


Application of Machine Learning for Drug-Target Interaction Prediction.
Exploring drug-target interactions by biomedical experiments requires a lot of human, financial, and material resources. To save time and cost to meet the needs of the present generation, machine learning methods have been introduced into the prediction of drug-target interactions. The large amount of available drug and target data in existing databases, the evolving and innovative computer technologies, and the inherent characteristics of various types of machine learning have made machine learning techniques the mainstream method for drug-target interaction prediction research. In this review, details of the specific applications of machine learning in drug-target interaction prediction are summarized, the characteristics of each algorithm are analyzed, and the issues that need to be further addressed and explored for future research are discussed. The aim of this review is to provide a sound basis for the construction of high-performance models.


Analysis of short- and long-term effects of adaptation in human postural control.
The short-term (i.e., days) and long-term (i.e., months) effects of adaptation to posturography examinations were investigated in 12 normal subjects who were repeatedly examined for five consecutive days and again after 90 days. The examinations were conducted both with eyes open and closed, and the perturbations were evoked by a pseudorandomly applied vibration stimulation to the calf muscles. The evoked anteroposterior responses were analyzed with a method considering adaptation in the slow changes in posture and in the stimulus-response relationship. Repetition of examinations on a daily basis revealed a gradual improvement of postural-control performance. The body sway induced by the stimulation was significantly reduced and the dynamical properties changed. Most of the improvements remained after 90 days, but some parameters such as the complexity of the control system used were increased to the initial level. The results confirm previous observations that postural control contains several partially independent adaptive processes, observed in terms of alteration of posture and as a progressive reduction of body sway induced by stimulation. The method used for the adaptation analysis in this study could be applied to analyze biological systems with multiple individual adaptive processes with different time courses or characteristics, or where the adaptation processes are related to multiple internal or external factors.


Unusual Indirect Nuclear Spin-Spin Exchange Coupling through Solvated Electron.
Solvated electrons have been found to exist in various media which also exhibit more intriguing properties such as superconductivity, nonlinear optical response, and so on. However, how they affect the nuclear spin properties has not been proven. In this work, we present the first detailed study on solvated-electron-triggered indirect nuclear spin-spin J-coupling using density functional theory calculations. Taking 19F as a probe, we verify the presence of unusual J couplings between two distant F atoms in HF-containing anionic clusters. These couplings occur "through solvated electron", rather than through conventional covalent bonds or space. Solvated electron can serve as an additional channel to efficiently realize long-range J-coupling between far separated nuclei because of its dispersivity and Rydberg character. The coupling magnitude strongly depends on the unique distribution of solvated electron and its second-order interaction with solvating HF units. This work provides novel insights into the mediating roles of electrons, possibly opening up potential applications based on weakly bound electrons.


[Comparison and agreement of the Cockcroft-Gault and MDRD equations to estimate glomerular filtration rate in diagnosis of occult chronic kidney disease].
The estimation of Glomerular Filtration Rate (GFR) by Cockroft-Gault or simplified MDRD functions is a powerful tool for the Chronic Kidney Disease (CKD) diagnosis. The aims of the present study are: 1)-To analyze the accuracy between Cockcroft-Gault and simplified MDRD equations in the Hidden Renal Failure (HRF) diagnosis; and 2)-To know the profile and coronary risk of patients diagnosed of HRF for each equation. Ten year follow-up of a cross sectional study. A total of 845 patients between 35 and 74 years old (average age 55 years, 56.7% female) without evidence of cardiovascular disease and taken care in a urban primary health center. HRF was defined as an estimated GFR <60 ml/min/1.73 m2 in patients with normal values of creatinine (<1.3 mg/dl in women and <1.4 mg/dl in men ) 8.3% of studied population had HRF by Cockroft-Gault formula and 11.6% using MDRD. The HRF patients diagnosticated with Cockroft-Gault function were older (67.4 vs 64.4 years, p<0.001) and had a higher coronary risk using either the original Framingham equation and REGICOR function. Furthermore, those HRF patients diagnosticated using MDRD function had a higher body mass index (29.6 vs 26.3 kg/m2, p<0.001) and were women in a greater percentage. Kappa index of agreement of these two equations for diagnosis of HRF was 0,55. The HRF patients diagnosticated exclusively by the use of Cockroft-Gault function were mainly men (75%), older (69.1 vs 61.9 years, p<0.001) and they had a high coronary risk in the Framingham equation (32.7%) and REGICOR function (13.1%) Cockroft-Gault and MDRD equations present a moderate agreement in HRF diagnosis (stage 3 of CKD) in patients between 35 and 74 years old. If we only use the MDRD function, a group of HRF patients would be excluded. This population was mainly male (75%), older (69 years old), with a high coronary risk estimated by original Framingham and REGICOR equations, and confirmed in the ten years follow-up of these patients.


Atu027, a liposomal small interfering RNA formulation targeting protein kinase N3, inhibits cancer progression.
We have previously described a small interfering RNA (siRNA) delivery system (AtuPLEX) for RNA interference (RNAi) in the vasculature of mice. Here we report preclinical data for Atu027, a siRNA-lipoplex directed against protein kinase N3 (PKN3), currently under development for the treatment of advanced solid cancer. In vitro studies revealed that Atu027-mediated inhibition of PKN3 function in primary endothelial cells impaired tube formation on extracellular matrix and cell migration, but is not essential for proliferation. Systemic administration of Atu027 by repeated bolus injections or infusions in mice, rats, and nonhuman primates results in specific, RNAi-mediated silencing of PKN3 expression. We show the efficacy of Atu027 in orthotopic mouse models for prostate and pancreatic cancers with significant inhibition of tumor growth and lymph node metastasis formation. The tumor vasculature of Atu027-treated animals showed a specific reduction in lymph vessel density but no significant changes in microvascular density.


Impact of perioperative blood transfusion on survival of patients undergoing laparoscopic gastrectomy for gastric cancer.
Previous studies have suggested that perioperative blood transfusion is associated with poor prognosis in patients undergoing radical gastrectomy for gastric cancer. The purpose of this study was to evaluate the impact of blood transfusion on the long-term survival of such patients. Short- and long-term outcomes were retrieved from a prospectively collected database of patients who underwent laparoscopic gastrectomy with radical intent for gastric cancer. A total of 309 patients who underwent laparoscopic radical gastrectomy were evaluated. Sixty-one (19.7%) received blood transfusions during or within 30 days after gastrectomy. These patients were typically older, had lower preoperative hemoglobin levels, had a more advanced cancer stage, had more than two comorbidities, had a higher rate of postoperative 30-day complications, and had a higher conversion rate. The overall survival (OS) (p=0.040) and disease-free survival (DFS) (p=0.004) were significantly decreased in patients who received blood transfusions. Multivariate analysis revealed that perioperative blood transfusion was not independently associated with decreased OS and DFS but that cancer stage and having more than two comorbidities were independent risk factors. Perioperative blood transfusion was associated with decreased OS and DFS in this patient series, but this apparently reflected the relatively poor medical condition of these patients requiring gastrectomy and was not a causative relationship.


Application Value of Combined Detection of NLR, PNI, D-Dimer, CD3+ T Lymphocytes, and CEA in Colorectal Cancer Screening.
To investigate the application value of combined detection of neutrophil-lymphocyte ratio (NLR), prognostic nutrition index (PNI), D-dimer (D-D), CD3+ T lymphocytes (CD3+ T), and carcinoembryonic antigen (CEA) in colorectal cancer screening. The study cohort comprised 187 colorectal cancer patients and 100 mixed hemorrhoids patients as controls from January 2019 to August 2021 at the Fifth Affiliated Hospital of Sun Yat-sen University. Comparing the levels of NLR, PNI, D-D, CD3+ T, and CEA between the two groups of subjects, drawing receiver operating characteristic (ROC) curve evaluates the efficacy of single and combined detection for colorectal cancer screening. Compared with the control group, the levels of NLR, D-D, and CEA in the colorectal cancer group were significantly increased, while the levels of PNI and CD3+ T were significantly decreased (P < 0.05). ROC curve analysis showed that the combined detection of NLR, PNI, D-D, CD3+ T, and CEA for colorectal cancer screening had an AUCROC of 0.943, a sensitivity of 84.49%, a specificity of 91.00%, and a Youden index of 0.75, and its screening efficacy was significantly superior to that of a single detection (P < 0.001). The combined detection of NLR, PNI, D-D, CD3+ T, and CEA has a high clinical application value for colorectal cancer and can provide a reference for early screening and auxiliary diagnosis of colorectal cancer.


rpoB sequence-based identification of Mycobacterium avium complex species.
The Mycobacterium avium complex (MAC) comprises slowly growing mycobacteria responsible for opportunistic infections and zoonoses. The ability to speciate MAC isolates in the clinical microbiology laboratory is critical for determining the organism implicated in clinical disease and for epidemiological investigation of the source of infection. Investigation of a 711 bp variable fragment of rpoB flanked by the Myco-F/Myco-R primers found a 0.7-5.1 % divergence among MAC reference strains, with Mycobacterium chimaera and Mycobacterium intracellulare being the most closely related. Using a 0.7 % divergence cut-off, 83 % of 100 clinical isolates, which had been previously identified by phenotypic characteristics and 16S-23S rDNA intergenic spacer (ITS) probing, were identified as M. avium, 8 % as M. intracellulare and 2 % as M. chimaera. The uniqueness of seven isolates, exhibiting < 99.3 % rpoB sequence similarity with MAC reference strains, was confirmed by 16S rDNA, ITS and hsp65 sequencing and phylogenetic analyses. Partial rpoB gene sequencing using the Myco-F/Myco-R primers permits one-step identification of MAC isolates at the species level and the detection of potentially novel MAC species.


Takayasu arteritis: clinical characteristics and the role of genetic factors in its pathogenesis.
Takayasu arteritis is a chronic vasculitis, the aetiology of which is still unknown. Several characteristic clinical manifestations have led scientists to consider the possibility of the genetic factors in the aetiology, conjecture which is supported by HLA analysis. Recent attention has focused on the different clinical manifestations among Asian and South American countries and further progress is likely to stem from international network studies.


Newborn survival in Uganda: a decade of change and future implications.
Each year in Uganda 141 000 children die before reaching their fifth birthday; 26% of these children die in their first month of life. In a setting of persistently high fertility rates, a crisis in human resources for health and a recent history of civil unrest, Uganda has prioritized Millennium Development Goals 4 and 5 for child and maternal survival. As part of a multi-country analysis we examined change for newborn survival over the past decade through mortality and health system coverage indicators as well as national and donor funding for health, and policy and programme change. Between 2000 and 2010 Uganda's neonatal mortality rate reduced by 2.2% per year, which is greater than the regional average rate of decline but slower than national reductions in maternal mortality and under-five mortality after the neonatal period. While existing population-based data are insufficient to measure national changes in coverage and quality of services, national attention for maternal and child health has been clear and authorized from the highest levels. Attention and policy change for newborn health is comparatively recent. This recognized gap has led to a specific focus on newborn health through a national Newborn Steering Committee, which has been given a mandate from the Ministry of Health to advise on newborn survival issues since 2006. This multi-disciplinary and inter-agency network of stakeholders has been able to preside over a number of important policy changes at the level of facility care, education and training, community-based service delivery through Village Health Teams and changes to essential drugs and commodities. The committee's comprehensive reach has enabled rapid policy change and increased attention to newborn survival in a relatively short space of time. Translating this favourable policy environment into district-level implementation and high quality services is now the priority.


Probabilistic Random Forest improves bioactivity predictions close to the classification threshold by taking into account experimental uncertainty.
Measurements of protein-ligand interactions have reproducibility limits due to experimental errors. Any model based on such assays will consequentially have such unavoidable errors influencing their performance which should ideally be factored into modelling and output predictions, such as the actual standard deviation of experimental measurements (σ) or the associated comparability of activity values between the aggregated heterogenous activity units (i.e., Ki versus IC50 values) during dataset assimilation. However, experimental errors are usually a neglected aspect of model generation. In order to improve upon the current state-of-the-art, we herein present a novel approach toward predicting protein-ligand interactions using a Probabilistic Random Forest (PRF) classifier. The PRF algorithm was applied toward in silico protein target prediction across ~ 550 tasks from ChEMBL and PubChem. Predictions were evaluated by taking into account various scenarios of experimental standard deviations in both training and test sets and performance was assessed using fivefold stratified shuffled splits for validation. The largest benefit in incorporating the experimental deviation in PRF was observed for data points close to the binary threshold boundary, when such information was not considered in any way in the original RF algorithm. For example, in cases when σ ranged between 0.4-0.6 log units and when ideal probability estimates between 0.4-0.6, the PRF outperformed RF with a median absolute error margin of ~ 17%. In comparison, the baseline RF outperformed PRF for cases with high confidence to belong to the active class (far from the binary decision threshold), although the RF models gave errors smaller than the experimental uncertainty, which could indicate that they were overtrained and/or over-confident. Finally, the PRF models trained with putative inactives decreased the performance compared to PRF models without putative inactives and this could be because putative inactives were not assigned an experimental pXC50 value, and therefore they were considered inactives with a low uncertainty (which in practice might not be true). In conclusion, PRF can be useful for target prediction models in particular for data where class boundaries overlap with the measurement uncertainty, and where a substantial part of the training data is located close to the classification threshold.


Intracranial Meningioma Diagnosed during Pregnancy Caused Maternal Death.
Brain tumors are rarely diagnosed during pregnancy. Accelerated growth of intracranial meningiomas during pregnancy sometimes requires urgent surgical intervention. We describe a 41-year-old pregnant woman with severe neurological decompensation requiring immediate neurosurgery. Cesarean section resulted in maternal death. Meningioma diagnosed during a viable pregnancy should be managed according to the severity of maternal neurological symptoms and gestational age of pregnancy. Early intervention for intracranial tumors during pregnancy may save maternal and fetal lives.


[A woman with a cavity in an intervertebral disc on the CT-scan].
The CT scan of a 77-year-old woman showed hypodense structures in the spine called vacuum phenomenon as an incidental finding. The cause in the majority of cases is the degeneration of tissue but vacuum phenomenon is also associated with other disorders. It is important to distinguish between benign causes and malignant causes. Unfamiliarity with this vacuum phenomenon may lead to suboptimal treatment.


Severe aquaporin 4-IgG-positive neuromyelitis optica with disseminated herpes zoster in a pregnant woman successfully treated with intravenous immunoglobulin.
A 26-year-old, 17-week pregnant woman developed aquaporin-4-IgG-positive severe longitudinally extensive transverse myelitis during the course of disseminated herpes zoster and became quadriparetic. She was unresponsive to high-dose intravenous methylprednisolone but became able to walk without assistance after intravenous immunoglobulin. One and a half months later, left optic neuritis developed but her vision improved with intravenous immunoglobulin. The only sequela was left T5 girdle sensation, and she delivered a healthy baby. Intravenous immunoglobulin may be a rescue therapy in aquaporin-4-IgG-positive neuromyelitis optica attacks in pregnant women, especially those with severe infections.


Transdermal delivery system of nanostructured lipid carriers loaded with Celastrol and Indomethacin: optimization, characterization and efficacy evaluation for rheumatoid arthritis.
Co-encapsulation of drugs provides a convenient means for treating different symptoms of a disease. Celastrol (Cel) shows potent anti-arthritic activity and Indomethacin (Indo) is effective in relieving inflammatory pain. Nanostructured lipid carriers loaded with Celastrol and Indomethacin (Cel-Indo-NLCs) were prepared by emulsification evaporation-solidification method, optimized by the Box-Behnken design and characterized by transmission electron microscopy (TEM), Fourier transform infrared (FTIR) and powder X-ray diffraction analysis (PXRD). Visualization of transdermal translocation of Cel-Indo-NLCs was achieved by confocal laser scanning microscope (CLSM). Further, Cel-Indo-NLCs were incorporated into Carbopol 940 for transdermal delivery. The in vitro studies were evaluated by using the Franz diffusion cells. Cel-Indo-NLCs depicted small particle size (26.92 ± 0.62 nm) and PDI (0.201 ± 0.01), high entrapment efficiency (96.56 ± 1.41%) and drug load (3.65 ± 0.05%). Moreover, Cel-Indo-NLCs showed prominent effect of decreasing paw oedema, inhibiting inflammation and pain by regulating the levels of IL-1β, TNF-α, β-endorphin and Substance P. After the administration of Cel-Indo-NLCs-gel, no skin irritation was observed in rats. There was no difference of gastrointestinal tract between different groups of rats when they were sacrificed. The histological analysis showed no renal and reproductive toxicity. Therefore, it can be concluded that co-encapsulation strategy based NLCs have the potential to provide safe transdermal delivery and are promising in treatment of pain and inflammation associated with rheumatoid arthritis.


A structural analysis of the myelin sheath in the central nervous system.
The cerebral white matter of rats subjected to a variety of noxious experimental conditions was examined in the electron microscope. Several unusual configurations of the myelin sheath are identified in addition to the usual configuration. These variations include the presence of (a) formed organelles within the inner and outer loops, (b) isolated islands of cytoplasm in unfused portions of the major dense lines, (c) apparently unconnected cell processes between the sheath and the axon, and (d) concentric, double myelin sheaths. A generalized model of the myelin sheath based on a hypothetical unrolling of the sheath is described. It consists of a shovel-shaped myelin sheet surrounded by a continuous thickened rim of cytoplasm. Most of the unusual myelin configurations are explained as simple variations on this basic theme. With the help of this model, an explanation of the formation of the myelin sheath is offered. This explanation involves the concept that myelin formation can occur at all cytoplasmic areas adjacent to the myelin proper and that adjacent myelin lamellae can move in relation to each other.


Natural variation of life-history traits, water use, and drought responses in Arabidopsis.
The ability of plants to acquire and use water is critical in determining life-history traits such as growth, flowering, and allocation of biomass into reproduction. In this context, a combination of functionally linked traits is essential for plants to respond to environmental changes in a coordinated fashion to maximize resource use efficiency. We analyzed different water-use traits in Arabidopsis ecotypes to identify functionally linked traits that determine water use and plant growth performance. Water-use traits measured were (i) leaf-level water-use efficiency (WUE i ) to evaluate the amount of CO 2 fixed relative to water loss per leaf area and (ii) short-term plant water use at the vegetative stage (VWU) as a measure of whole-plant transpiration. Previously observed phenotypic variance in VWU, WUE i and life-history parameters, highlighted C24 as a valuable ecotype that combined drought tolerance, preferential reproductive biomass allocation, high WUE i , and reduced water use. We therefore screened 35 Arabidopsis ecotypes for these parameters, in order to assess whether the phenotypic combinations observed in C24 existed more widely within Arabidopsis ecotypes. All parameters were measured on a short dehydration cycle. A segmented regression analysis was carried out to evaluate the plasticity of the drought response and identified the breakpoint as a reliable measure of drought sensitivity. VWU was largely dependent on rosette area, but importantly the drought sensitivity and plasticity measures were independent of the transpiring leaf surface. A breakpoint at high rSWC indicated a more drought-sensitive plant that closed stomata early during the dehydration cycle and consequently showed stronger plasticity in leaf-level WUE i parameters. None of the sensitivity, plasticity, or water-use measurements were able to predict the overall growth performance; however, there was a general trade-off between vegetative and reproductive biomass. PCA and hierarchical clustering revealed that C24 was unique among the 35 ecotypes in uniting all the beneficial water use and stress tolerance traits, while also maintaining above average plant growth. We propose that a short dehydration cycle, measuring drought sensitivity and VWU is a fast and reliable screen for plant water use and drought response strategies.


Isolation and partial characterization of a murine cell surface glycoprotein with affinity for exogenously added beta 2-microglubulin.
Exogenously added beta 2-microglobulin (beta 2m) binds to a variety of murine cell types. The 'receptor' for beta 2m has been isolated. The purified 'receptor' comprised a 48,000-dalton chain and occasionally a 25,000-dalton component. Direct crosslinking of beta 2m to the receptor on intact cells gave rise to a single 60,000-dalton beta 2m-'receptor' complex. The molecular characteristics of the 'receptor' were considerably changed on binding beta 2m. The size of the beta 2m-'receptor' complex was increased partly due to enhanced binding of deoxycholate. The 'receptor' was less easily degraded by proteases when beta 2m was bound then when free. The solubilized 'receptor' reacted with a heteroantiserum raised against H-2K and D antigens but did not exhibit any alloantigenic determinants shared with H-2K, D or Ia antigens.


Polymorphisms of dopamine-beta-hydroxylase in ADHD children.
ADHD is a multifactorial disorder clinically characterized by inattentiveness, impulsivity and hyperactivity. The occurrence of this disorder varies between 3 and 6% of the child population, with boys predominating over girls at a ratio of 3 : 1 or more. Dysfunction or imbalance between the dopaminergic and noradrenergic systems of neurotransmitters can play a key role in the ADHD pathophysiology. Alteration of the dopamine/noradrenaline levels can result in hyperactivity. DBH is an enzyme responsible for the conversion of dopamine into noradrenaline. The DBH protein is released in response to stimulation. DBH activity, derived largely from sympathetic nerves, can be measured in human plasma. Patients with ADHD showed decreased activities of DBH in serum and urine. Low DBH levels correlate indirectly with the seriousness of the hyperkinetic syndrome in children (Galvin et al., 1995, 1997). In the DBH gene, the G444A, G910T, C1603T, C1912T, C-1021T, 5'-ins/del and TaqI polymorphisms occur frequently and may affect the function of gene products or modify gene expression and thus influence the progression of ADHD. This article reviews the DBH itself and polymorphisms in the DBH gene that influence the DBH activity in the serum and the CSF level of DBH. All those are evaluated in connection with ADHD.


Tuberculous pseudoaneurysm of the ascending aorta.
Increase in the incidence of drug resistance and association with HIV has led to a resurgence of tuberculosis. However, tubercular arteritis continues to remain a rare entity with a prelidection for the thoracic aorta. We report a tubercular ascending aortic pseudoaneurysm in a patient already on treatment for disseminated tuberculosis who underwent successful surgical repair and also review literature pertaining to this entity.


Developmentally Arrested Precursors of Pontine Neurons Establish an Embryonic Blueprint of the Drosophila Central Complex.
Serial electron microscopic analysis shows that the Drosophila brain at hatching possesses a large fraction of developmentally arrested neurons with a small soma, heterochromatin-rich nucleus, and unbranched axon lacking synapses. We digitally reconstructed all 802 "small undifferentiated" (SU) neurons and assigned them to the known brain lineages. By establishing the coordinates and reconstructing trajectories of the SU neuron tracts, we provide a framework of landmarks for the ongoing analyses of the L1 brain circuitry. To address the later fate of SU neurons, we focused on the 54 SU neurons belonging to the DM1-DM4 lineages, which generate all columnar neurons of the central complex. Regarding their topologically ordered projection pattern, these neurons form an embryonic nucleus of the fan-shaped body ("FB pioneers"). Fan-shaped body pioneers survive into the adult stage, where they develop into a specific class of bi-columnar elements, the pontine neurons. Later born, unicolumnar DM1-DM4 neurons fasciculate with the fan-shaped body pioneers. Selective ablation of the fan-shaped body pioneers altered the architecture of the larval fan-shaped body primordium but did not result in gross abnormalities of the trajectories of unicolumnar neurons, indicating that axonal pathfinding of the two systems may be controlled independently. Our comprehensive spatial and developmental analysis of the SU neurons adds to our understanding of the establishment of neuronal circuitry.


Multi-Wavelength Photoplethysmography Enabling Continuous Blood Pressure Measurement With Compact Wearable Electronics.
To fight the "silent killer" hypertension, continuous blood pressure (BP) monitoring has been one of the most desired functions in wearable electronics. However, current BP measuring principles and protocols either involve a vessel occlusion process with a cuff or require multiple sensing nodes on the body, which makes it difficult to implement them in compact wearable electronics like smartwatches and wristbands with long-term wearability. In this work, we proposed a highly compact multi-wavelength photoplethysmography (MWPPG) module and a depth-resolved MWPPG approach for continuous monitoring of BP and systemic vascular resistance (SVR). By associating the wavelength-dependent light penetration depth in the skin with skin vasculatures, our method exploited the pulse transit time (PTT) on skin arterioles for tracking SVR (n = 20). Then, we developed an arteriolar PTT-based method for beat-to-beat BP measurement. The BP estimation accuracy of the proposed arteriolar PTT method was validated against Finometer (n = 20) and the arterial line (n = 4). The correlation between arteriolar PTT and SVR was theoretically deduced and experimentally validated on 20 human subjects performing various maneuvers. The proposed arteriolar PTT-based method outperformed the traditional arterial PTT-based method with better BP estimation accuracy and simpler measurement setup, i.e., with a single sensing node. The proposed depth-resolved MWPPG method can provide accurate measurements of SVR and BP, which are traditionally difficult to measure in a noninvasive or continuous fashion. This MWPPG work provides the wearable healthcare electronics of compact size with a low-cost and physiology-based solution for continuous measurement of BP and SVR.


[Comparative analysis of antirestriction activity of R64 ArdA and ArdB proteins].
Antirestriction proteins ArdA and ArdB are specific inhibitors of the type I restriction-modification enzymes. The transmissible plasmid R64 ardA and yfeB (ardB) genes were cloned in pUC18 and pZE21 vectors. It was shown that the R64 ArdA and ArdB proteins inhibit only restriction activity of the type I restriction-modification enzyme (EcoKI) in Escherichia coli K12 cells. The dependence of the effectiveness of the antirestriction activity of the ArdA and ArdB proteins on the intracellular concentration was determined. Antirestriction activity of ArdB is independent from the ClpXP protease. Transcription of yfeB (ardB) gene in R64 plasmid is realized from the yfeA promoter.


Reemergence of foot-and-mouth disease, South Korea, 2000-2011.
Five outbreaks of foot-and-mouth disease have occurred in South Korea during 2000-2011. Macro-analysis of these outbreaks showed a correlation with outbreaks in countries in eastern Asia. Genetic analyses of food-and-mouth disease viruses in South Korea showed a correlation with viruses that are prevalent in neighboring countries.


Medication Safety in Primary Care Practice: results from a PPRNet quality improvement intervention.
Reducing medication errors is a fundamental patient safety goal; however, few improvement interventions have been evaluated in primary care settings. The Medication Safety in Primary Care Practice project was designed to test the impact of a multimethod quality improvement intervention on 5 categories of preventable prescribing and monitoring errors in 20 Practice Partner Research Network (PPRNet) practices. PPRNet is a primary care practice-based research network among users of a common electronic health record (EHR). The intervention was associated with significant improvements in avoidance of potentially inappropriate therapy, potential drug-disease interactions, and monitoring of potential adverse events over 2 years. Avoidance of potentially inappropriate dosages and drug-drug interactions did not change over time. Practices implemented a variety of medication safety strategies that may be relevant to other primary care audiences, including use of EHR-based audit and feedback reports, medication reconciliation, decision-support tools, and refill protocols.


Effects of pertussis toxin on the alpha 2-adrenoceptor-inhibitory GTP-binding protein-adenylate cyclase system in rat brain: pharmacological and neurochemical studies.
Behavioral excitement and the increase in locomotion were observed in male adult rats four days after an intraventricular injection of 5 micrograms pertussis toxin (IAP). Clonidine (100 micrograms/kg s.c.)-induced locomotor hypoactivity was not observed in animals pretreated with 1 and 5 micrograms IAP. IAP caused a significant (P less than 0.05) decrease in the KD value of [3H]clonidine binding and enhanced GTP (1 microM)-induced decrease in the binding to cortical membranes from rat brain. In addition, the inhibition of adenylate cyclase induced by alpha 2-receptor stimulation (100 microM adrenaline plus 100 microM propranolol) was completely suppressed in the cerebral cortical membranes by IAP pretreatment. It is suggested that the system consisting of alpha 2-receptor, the inhibitory GTP-binding protein (Ni) and adenylate cyclase inhibits some animal behaviors and cyclic AMP formation. Moreover, IAP seems to inactivate Ni, subsequently producing behavioral excitement and it inhibits clonidine-induced sedation.


Reproductive outcomes and nononcologic complications after radioactive iodine ablation for well-differentiated thyroid cancer.
Radioactive iodine (RAI) ablation is frequently performed after initial surgery for well-differentiated thyroid cancer (WDTC). We examined the frequency and timing of childbirth as well as nononcologic complications after RAI ablation for WDTC on a population level. A retrospective cohort study of 25,333 patients (18,850 women) with WDTC was performed using the California Cancer Registry and California Office of Statewide Health Planning and Development database, 1999-2008. The primary outcomes were birthrate and median time to first live birth among women of childbearing age. Secondary outcomes were nononcologic diagnoses occurring outside the acute setting (>30 days) after ablation. RAI ablation did not affect birthrate among women in the full dataset. However, in subgroup analyses, birthrate among women age 35-39 was significantly decreased in those who received RAI versus those who did not (11.5 versus 16.3 births per 1000 woman-years, p<0.001). Median time to first live birth after diagnosis of WDTC was prolonged among women who received RAI compared to those who did not (34.5 versus 26.1 months; p<0.0001). When 5-year age groups were examined individually, delay to first live birth was observed in women age 20-39 (p<0.05). This remained significant after adjustment for tumor characteristics, socioeconomic status, and marital status. The only nononcologic, nonreproductive adverse effect associated with RAI ablation was an increased rate of nasolacrimal stenosis (RR 3.44, p<0.0001). RAI ablation is associated with delayed childbearing in women across most of the reproductive lifespan, and with decreased birthrate in the late reproductive years. The underlying mechanism likely involves physician recommendation to delay pregnancy, as well as a potential impact of RAI on both reproductive choice and reproductive health. Further investigation is merited.


Are gas-phase models of interstellar chemistry tenable? The case of methanol.
We consider the case of methanol production in cold dark clouds, also known as quiescent cores, for which recent work shows that a purely gas-phase synthesis is unlikely to produce a sufficient amount to explain the observational fractional abundance of approximately 10(-9). Moreover, recent experiments appear to confirm a previous hypothesis that methanol can be formed on cold grain surfaces by the hydrogenation of CO via successive reactions with hydrogen atoms. In this paper we consider two ways of including the surface formation of methanol into chemical models of cold dark clouds. First, we use a gas-phase model and artificially include the surface formation of methanol in the same manner that the formation of molecular hydrogen is included. Secondly, we utilize a gas-grain code with a new mechanism for desorption following exothermic chemical reactions on grain surfaces. The latter method can reproduce the observed fractional abundance of gas-phase methanol and many other gas-phase species in the well-studied cold dark cloud TMC1-CP but the best fit to the observational data occurs at times significantly later than at ages estimated from gas-phase models.


Computerized patient identification for the EMBRACA clinical trial using real-time data from the PRAEGNANT network for metastatic breast cancer patients.
As breast cancer is a diverse disease, clinical trials are becoming increasingly diversified and are consequently being conducted in very small subgroups of patients, making study recruitment increasingly difficult. The aim of this study was to assess the use of data from a remote data entry system that serves a large national registry for metastatic breast cancer. The PRAEGNANT network is a real-time registry with an integrated biomaterials bank that was designed as a scientific study and as a means of identifying patients who are eligible for clinical trials, based on clinical and molecular information. Here, we report on the automated use of the clinical data documented to identify patients for a clinical trial (EMBRACA) for patients with metastatic breast cancer. The patients' charts were assessed by two independent physicians involved in the clinical trial and also by a computer program that tested patients for eligibility using a structured query language script. In all, 326 patients from two study sites in the PRAEGNANT network were included in the analysis. Using expert assessment, 120 of the 326 patients (37 %) appeared to be eligible for inclusion in the EMBRACA study; with the computer algorithm assessment, a total of 129 appeared to be eligible. The sensitivity of the computer algorithm was 0.87 and its specificity was 0.88. Using computer-based identification of patients for clinical trials appears feasible. With the instrument's high specificity, its application in a large cohort of patients appears to be feasible, and the workload for reassessing the patients is limited.


Mechanisms of strain-mediated mesenchymal stem cell apoptosis.
Mechanical conditioning of mesenchymal stem cells (MSCs) has been adopted widely as a biophysical signal to aid tissue engineering applications. The replication of in vivo mechanical signaling has been used in in vitro environments to regulate cell differentiation, and extracellular matrix synthesis, so that both the chemical and mechanical properties of the tissue-engineered construct are compatible with the implant site. While research in these areas contributes to tissue engineering, the effects of mechanical strain on MSC apoptosis remain poorly defined. To evaluate the effects of uniaxial cyclic tensile strain on MSC apoptosis and to investigate mechanotransduction associated with strain-mediated cell death, MSCs seeded on a 2D silicone membrane were stimulated by a range of strain magnitudes for 3 days. Mechanotransduction was investigated using the stretch-activated cation channel blocker gadolinium chloride, the L-type voltage-activated calcium channel blocker nicardipine, the c-jun NH(2)-terminal kinase (JNK) blocker D-JNK inhibitor 1, and the calpain inhibitor MDL 28170. Apoptosis was assessed through DNA fragmentation using the terminal deoxynucleotidyl transferase mediated-UTP-end nick labeling method. Results demonstrated that tensile strains of 7.5% or greater induce apoptosis in MSCs. L-type voltage-activated calcium channels coupled mechanical stress to activation of calpain and JNK, which lead to apoptosis through DNA fragmentation. The definition of the in vitro boundary conditions for tensile strain and MSCs along with a proposed mechanism for apoptosis induced by mechanical events positively contributes to the development of MSC biology, bioreactor design for tissue engineering, and development of computational methods for mechanobiology.


Immature granulocytes predict severe acute pancreatitis independently of systemic inflammatory response syndrome.
Early prediction of severity of acute pancreatitis (AP) by a simple parameter that positively correlates with the activation stage of the immune system would be very helpful because it could influence the management and improve the outcome. Tumor necrosis factor α (TNF-α) and interleukin-1 (IL-1) play a critical role in the pathogenesis systemic inflammatory response syndrome (SIRS) and severity of AP. One of the effects of IL-1 and TNF-α is an increase in the number of immature granulocytes (IGs) in the peripheral blood. To assess whether the IGs% in plasma could be an independent marker of AP severity. A cohort of 77 patients with AP were prospectively enrolled in the study. The IGs were measured from whole blood samples obtained from the first day of hospitalization using an automated analyser. We observed 44 (57%) patients with mild AP, 21 (27%) patients with moderate severe AP (SAP) and 12 (16%) patients with SAP. The cut-off value of IGs was 0.6%. The IGs > 0.6% had a sensitivity, specificity, and positive and negative predictive value of 100%, 96%, 85.7%, and 100%, respectively (area under the curve (AUC) = 0.98). On admission, SIRS was present in 25 (32%) patients. We found that in patients who fulfilled at least two criteria for SIRS, SAP could be predicted with 75% sensitivity and 75.4% specificity, positive predictive value 36%, negative predictive value 94.2%. The IGs% as a routinely obtained marker appears to be a promising, independent biomarker and a better predictor of early prognosis in SAP than SIRS and white blood cell.


Differences in Psychoactive Substance Abuse Between Youths Residing in and Outside Conflict Zones as a Function of Level of Religiosity and Political Commitment.
The aim of the present study was to examine the effect of the unique characteristics of residing in security and political conflict zones on the willingness to use and on the actual abuse of psychoactive substances. The study focuses on the differences between youths residing in and outside conflict zones in Israel. The present study examines the link between the adolescents' level of psychoactive substance abuse and town size as well as the youths' level of ideological commitment and religiosity. 1032 adolescents aged 14-18 participated in the study. 595 (57%) lived in the nonconflict zones and 437 (43%) in conflict zones. The findings reveal that the level of psychoactive substance abuse among youths residing in conflict zones is significantly lower than that found among youths living outside conflict zones. Moreover, although town size and level of religiosity are linked to psychoactive substance abuse, no such link was found with the level of ideological commitment or place of residence (within or outside conflict zones). The study findings underscore the important effect of social supervision and perceived norms in the adolescents' environment with regard to their willingness to use psychoactive substances and to their actual abuse of such substances.


CHWs trained in ARI management.
Regular supervision and refresher trainings were the key to the success of a CHW (community health worker) training program in rural Bolivia. Since 1988, with the support of PLAN International, volunteer CHWs have been trained in 115 villages in Sucre, a rural health area lacking adequate health centers. CHWs educate the community, diagnose and treat pneumonia and refer severe cases to health centers or hospitals. CHWs who were already working on diarrheal disease control were chosen for the acute respiratory infection (ARI) case management training. A 3-day training program was organized for individual CHWs in their own homes and communities. The course included practicing on real ARI cases under the trainer's supervision. Since the program started, community respect for CHWs has risen. In one remote village, community leaders reported a marked improvement in child survival. Factors which explain the positive effects of CHWs include: a limited number of clearly defined tasks, provision of one-on-one appropriate training, periodic refresher courses, and continuous supervision. The main problems have been a lack of constant supply of essential drugs and some CHWs over-diagnosing pneumonia. However, once diagnosis is made, CHWs are careful about giving the correct antibiotic doses and instructions to mothers. Refresher training and supervision have helped to correct these initial problems. PLAN International and the Ministry of Health have organized supervision and training meetings every 2 months. The CHWs bring to these meetings reports of children treated and referred. Case management is analyzed, resupply of essential medicines is arranged and those with special problems are scheduled for a supervisory visit.


Bosentan Inducing Autoimmune Hepatitis in a Patient with Idiopathic Pulmonary Arterial Hypertension.
A 41-year-old woman diagnosed with idiopathic pulmonary hypertension presented symptoms despite the use of vasodilators, requiring treatment with bosentan. Previously, the patient had no signs of autoimmunity and had normal liver function. After three years of bosentan use, aminotransferase levels increased, without improvement after bosentan suspension, leading to complementary investigation. The diagnosis of autoimmune hepatitis was confirmed by biopsy, already in the stage of cirrhosis. In conclusion, in case of aminotransferase levels that remain persistently elevated, despite the reduction in doses and/or suspension of bosentan, autoimmune hepatitis must be investigated and treated urgently due to possibly rapid progression to cirrhosis..


Photobiological transformation of hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) using Rhodobacter sphaeroides.
Pump-and-treat strategies for groundwater containing explosives may be necessary when the contaminated water approaches sensitive receptors. This project investigated bacterial photosynthesis as a strategy for ex situ treatment, using light as the primary energy source to facilitate RDX transformation. The objective was to characterize the ability of photosynthetic Rhodobacter sphaeroides (strain ATCC(®) 17023 ™) to transform the high-energy explosive RDX. R. sphaeroides transformed 30 μM RDX within 40 h under light conditions; RDX was not fully transformed in the dark (non-photosynthetic conditions), suggesting that photosynthetic electron transfer was the primary mechanism. Experiments with RDX demonstrated that succinate and malate were the most effective electron donors for photosynthesis, but glycerol was also utilized as a photosynthetic electron donor. RDX was transformed irrespective of the presence of carbon dioxide. The electron shuttling compound anthraquinone-2,6-disulfonate (AQDS) increased transformation kinetics in the absence of CO2, when the cells had excess NADPH that needed to be re-oxidized because there was limited CO2 for carbon fixation. When CO2 was added, the cells generated more biomass, and AQDS had no stimulatory effect. End products indicated that RDX carbon became CO2, biomass, and a soluble, uncharacterized aqueous metabolite, determined using (14)C-labeled RDX. These data are the first to suggest that photobiological explosives transformation is possible and will provide a framework for which phototrophy can be used in environmental restoration of explosives contaminated water.


Effect of amiodarone in the Wolff-Parkinson-White syndrome.
The effect of amiodarone in the Wolff-Parkinson-White syndrome was studied with programmed electrical stimulation of the heart in 15 patients. All 15 patients had circus movement tachycardias; 7 also had atrial fibrillation. Programmed electrical stimulation was performed before and after 14 days of oral administration of amiodarone. The effective refractory period of the accessory pathway lengthened in an atrioventricular direction in all patients and in a ventriculoatrial direction in eight patients. The effective refractory period of the atrium and ventricle lengthened in 14 and 12 patients, respectively. After administration of amiodarone, circus movement tachycardia could no longer be initiated in five patients. The zone of tachycardia narrowed in four patients, did not change in two and increased in seven. The effect of amiodarone on initiation of circus movement tachycardia could be related to differences in effect of the drug and in the mechanism of tachycardia in individual patients. In all patients in whom tachycardias could still be initiated after treatment with amiodarone the heart rate during tachycardia was slower than before treatment. This slowing was caused by a decrease in conduction velocity of the circulatory wave in different parts of the tachycardia circuit. The effect of amiodarone in prolonging the refractory period of the accessory pathway makes this drug especially useful in patients with the Wolff-Parkinson-White syndrome and atrial fibrillation.


Two-slot coiled coaxial cable resonator: reaching critical coupling at a reduced number of coils.
This paper reports the experimental demonstration of a coiled coaxial cable resonator capable of meeting the critical coupling condition using a reduced number of coils relative to previously reported coiled resonators. By introducing a second slot along the length of the device, a two-slot coiled coaxial cable resonator was fabricated and critical coupling observed at 22 turns. An additional device with one-slot, but otherwise identically constructed, was also fabricated. After 44 turns, the one-slot device had yet to reach critical coupling. An ultrahigh signal-to-noise ratio (greater than 70 dB) was observed at critical coupling of the two-slot device. This reduction in number of slots necessary to reach critical coupling, and the corresponding reduction of physical length of the device, makes this demonstration of the control of critical coupling a potentially important step towards the successful application of coiled coaxial cable resonators to microwave communication and robust sensing applications.


Topochemical synthesis of Co-Fe layered double hydroxides at varied Fe/Co ratios: unique intercalation of triiodide and its profound effect.
Co-Fe layered double hydroxides at different Fe/Co ratios were synthesized from brucite-like Co(2+)(1-x)Fe(2+)(x)(OH)(2) (0 ≤ x ≤ 1/3) via oxidative intercalation reaction using an excess amount of iodine as the oxidizing agent. A new redoxable species: triiodide (I(3)(-)), promoted the formation of single-phase Co-Fe LDHs. The results point to a general principle that LDHs with a characteristic ratio of total trivalent and divalent cations (M(3+)/M(2+)) at 1/2 may be the most stable in the oxidative intercalation procedure. At low Fe content, e.g., starting from Co(2+)(1-x)Fe(2+)(x)(OH)(2) (x < 1/3), partial oxidation of Co(2+) to Co(3+) takes place to reach the M(3+)/M(2+) threshold of 1/2 in as-transformed Co(2+)(2/3)-(Co(3+)(1/3-x)-Fe(3+)(x)) LDHs. Also discovered was the cointercalation of triiodide and iodide into the interlayer gallery of as-transformed LDH phase, which profoundly impacted the relative intensity ratio of basal Bragg peaks as a consequence of the significant X-ray scattering power of triiodide. In combination with XRD simulation, the LDH structure model was constructed by considering both the host layer composition/charge and the arrangement of interlayer triiodide/iodide. The work provides a clear understanding of the thermodynamic and kinetic factors associated with the oxidative intercalation reaction and is helpful in elucidating the formation of LDH structure in general.


Differential Influence of Early Life and Adult Stress on Urogenital Sensitivity and Function in Male Mice.
Experiences of adverse childhood events have been associated with improper output of the hypothalamic-pituitary-adrenal (HPA) axis in adulthood, as well as development of comorbid functional pain disorders. Symptoms of chronic prostatitis/chronic pelvic pain syndrome frequently overlap with those of interstitial cystitis/painful bladder syndrome and symptom severity is often triggered by stress. The objective of this study was to investigate the influence early life stress and acute adult stress on (1) perigenital sensitivity, (2) micturition, (3) anhedonia, and (4) HPA axis regulation and output in male C56Bl/6 mice. Neonatal maternal separation (NMS) was performed for 3 h a day from postnatal day 1 to 21 and naïve pups remained unhandled during this time. As adults, male mice were tested for referred prostate sensitivity and micturition patterning prior to and 1 and 8 days after exposure to 1 h of water avoidance stress (WAS). Following testing, prostate and bladder tissues were used for mast cell and Western blot analysis and RT-PCR was performed on mRNA from hypothalamus, amygdala, and hippocampus. Serum corticosterone (CORT) was also measured by enzyme-linked immunosorbent assay (ELISA). A significant increase in perigenital sensitivity and micturition frequency was observed in NMS mice and these measures were exacerbated by WAS exposure. Exposure to NMS significantly increased mast cell degranulation in both the bladder and prostate. Mast cell degranulation was also increased in naïve prostate tissue following WAS exposure. Cytokine mRNA levels were influenced by both NMS and WAS exposure, though WAS had a larger impact on central gene expression. Protein levels of CRF1 were differentially regulated by NMS and WAS in the bladder and prostate and serum CORT levels were significantly diminished following stress exposure. Taken together, these data suggest that NMS results in neurogenic inflammation and hypersensitivity within the urogenital organs, coupled with diminished gene expression and output from the HPA axis. Future studies of NMS in male mice may provide a useful tool as a preclinical model of male chronic urological pain syndromes for investigating potential pharmacological and interventional therapies.


Noncanonical α/γ Backbone Conformations in RNA and the Accuracy of Their Description by the AMBER Force Field.
The sugar-phosphate backbone of RNA can exist in diverse rotameric substates, giving RNA molecules enormous conformational variability. The most frequent noncanonical backbone conformation in RNA is α/γ = t/t, which is derived from the canonical backbone by a crankshaft motion and largely preserves the standard geometry of the RNA duplex. A similar conformation also exists in DNA, where it has been extensively studied and shown to be involved in DNA-protein interactions. However, the function of the α/γ = t/t conformation in RNA is poorly understood. Here, we present molecular dynamics simulations of several prototypical RNA structures obtained from X-ray and NMR experiments, including canonical and mismatched RNA duplexes, UUCG and GAGA tetraloops, Loop E, the sarcin-ricin loop, a parallel guanine quadruplex, and a viral pseudoknot. The stability of various noncanonical α/γ backbone conformations was analyzed with two AMBER force fields, ff99bsc0χOL3 and ff99bsc0χOL3 with the recent εζOL1 and βOL1 corrections for DNA. Although some α/γ substates were stable with seemingly well-described equilibria, many were unstable in our simulations. Notably, the most frequent noncanonical conformer α/γ = t/t was unstable in both tested force fields. Possible reasons for this instability are discussed. Our work reveals a potentially important artifact in RNA force fields and highlights a need for further force field refinement.


The gene encoding peripheral myelin protein zero is located on mouse chromosome 1.
We have used somatic cell hybrids to map the gene encoding protein zero (P0), the major structural protein of peripheral myelin. Analysis of Southern blots of DNA obtained from these hybrids allows us to unambiguously assign the P0 gene to mouse chromosome 1. This observation indicates that mutations in the P0 gene do not account for Trembler, a chromosome 11 mutation that specifically affects myelination in the peripheral nervous system.


Odor discrimination using insect electroantennogram responses from an insect antennal array.
Insects have a highly developed olfactory sensory system, mainly based in their antennae, for the detection and discrimination of volatile compounds in the environment. Electroantennogram (EAG) response profiles of five different insect species, Drosophila melanogaster, Heliothis virescens, Helicoverpa zea, Ostrinia nubilalis and Microplitis croceipes, showed different, species-specific EAG response spectra to 20 volatile compounds tested. The EAG response profiles were then reconstructed for each compound across the five insect species. Most of the compounds could be distinguished by comparing the response spectra. We then used a four-antenna array, called a Quadro-probe EAG, to see if we could discriminate among odorants based on the relative EAG amplitudes evoked when the probe was placed in plumes in a wind tunnel and in a field. Stable EAG responses could be simultaneously and independently recorded with four different insect antennae mounted on the Quadro-probe, and different volatile compounds could be distinguished in real time by comparing relative EAG responses with a combination of differently tuned insect antennae. Regardless of insect species or EAG amplitudes, antennae on the Quadro-probe maintained their responsiveness with higher than 1 peak/s of time resolution.


Group A streptococcal bacteraemia in Yorkshire and the Humber: evidence of another problematic infection among injecting drug users.
It has been estimated that in England and Wales, in 2002, 15% of all invasive group A streptococcal (GAS) cases were amongst injecting drug users (IDUs). This study sought to clarify the extent of this problem in the Yorkshire and Humber region by asking laboratories for further information on reported cases. In our region we found that there was a near doubling of cases, from 64 reports of GAS bacteraemia in the first six months of 2001, to 121 reports in the same period of 2003. We estimated that 34% of all GAS cases, more than twice the previous national estimate, occurred in IDUs and that the proportion of cases occurring in IDUs nearly doubled from 2001 to 2002. Our findings should be viewed within the context of the increasing reports of several other problematic infections in IDUs.


Control of COX-2 gene expression through peroxisome proliferator-activated receptor gamma in human cervical cancer cells.
The peroxisome proliferator-activated receptor-gamma (PPARgamma), a ligand-dependent transcription factor belonging to the family of nuclear receptors, has been implicated in the control of cyclooxygenase (COX) 2 expression in some tissue, although the exact mechanism(s) of this activity has not been elucidated. In this study we explored the possible mechanism(s) of control of COX-2 gene expression through PPARgamma signaling in human cervical cancer. Using primary human cervical tissues and the CaSki human cervical cancer cell line, we assayed for PPARgamma and COX-2 mRNA expression by reverse transcription-PCR. Nuclear protein binding activities to three response elements located in the COX-2 promoter [nuclear factor kappaB (NFkappaB), cyclic AMP response element, and activator protein (AP)-2] were measured by gel mobility shift assays. We used transient transfection assays with COX-2 promoter reporter gene constructs to determine the regulatory sites in this promoter, which mediates PPARgamma regulation of COX-2 activity. We showed, for the first time, that primary human cervical cancer tissues express PPARgamma. Using CaSki cells, we demonstrated that COX-2 and PPARgamma mRNA levels were inversely regulated by PPARgamma ligands in that these compounds up-regulated PPARgamma but down-regulated COX-2. In contrast, epidermal growth factor (EGF), a potent activator of COX-2, decreased PPARgamma mRNA levels. This down-regulation of PPARgamma mRNA by EGF was blocked in the presence of NS-398, a selective COX-2 inhibitor. PPARgamma ligands suppressed the binding activities of AP-1 (binding to CRE) and NFkappaB but not AP-2. Transient transfection results indicated that EGF stimulated whereas PPARgamma ligands inhibited COX-2 promoter (-327/+59) activity. This effect by PPARgamma ligands on the COX-2 promoter was blocked when the CRE, but not the NFkappaB, binding site was mutagenized. Cervical cancer cells express readily detectable levels of PPARgamma. There is reciprocal negative regulation between COX-2 and PPARgamma signaling in human cervical cancer cells. The ability of PPARgamma ligands to inhibit COX-2 appears to be mediated predominantly through inhibition of AP-1 protein binding to the CRE site in the COX-2 promoter.


Role of microRNAs 221/222 on statin induced nitric oxide release in human endothelial cells.
Nitric oxide (NO) has been largely associated with cardiovascular protection through improvement of endothelial function. Recently, new evidence about modulation of NO release by microRNAs (miRs) has been reported, which could be involved with statin-dependent pleiotropic effects, including anti-inflammatory properties related to vascular endothelium function. To evaluate the effects of cholesterol-lowering drugs including the inhibitors of cholesterol synthesis, atorvastatin and simvastatin, and the inhibitor of cholesterol absorption ezetimibe on NO release, NOS3 mRNA expression and miRs potentially involved in NO bioavailability. Human umbilical vein endothelial cells (HUVEC) were exposed to atorvastatin, simvastatin or ezetimibe (0 to 5.0 μM). Cells were submitted to total RNA extraction and relative quantification of NOS3 mRNA and miRs -221, -222 and -1303 by qPCR. NO release was measured in supernatants by ozone-chemiluminescence. Both statins increased NO levels and NOS3 mRNA expression but no influence was observed for ezetimibe treatment. Atorvastatin, simvastatin and ezetimibe down-regulated the expression of miR-221, whereas miR-222 was reduced only after the atorvastatin treatment. The magnitude of the reduction of miR-221 and miR-222 after treatment with statins correlated with the increment in NOS3 mRNA levels. No influence was observed on the miR-1303 expression after treatments. NO release in endothelial cells is increased by statins but not by the inhibitor of cholesterol absorption, ezetimibe. Our results provide new evidence about the participation of regulatory miRs 221/222 on NO release induction mediated by statins. Although ezetimibe did not modulate NO levels, the down-regulation of miR-221 could involve potential effects on endothelial function.


Occurrence of residual disease in specimens of re-excision surgery in patients with positive margins of primary quadrantectomy.
Performing a re-intervention following a positive margin after primary lumpectomy in patients with breast cancer entails several disadvantages such as additional costs and postponing the follow-up treatments. In the present study, we sought to measure the incidence rate of residual disease in specimens taken from breast cancer patients who had positive margins after quadrantectomy and also compare the clinical and pathological factors between patients with and without a residual disease after the secondary surgery. All of the medical records of patients undergoing quadrantectomy from December 1994 to December 2019 were collected from Shiraz Breast Cancer Registry (SBCR). Patients were divided into two subgroups of patients with and without residual disease from the secondary surgery and also with and without positive margin from the first operation. Two groups were compared in terms of all clinicopathological factors. The records of 4843 patients undergoing quadrantectomy were reviewed, of which 132 (2.3%) had involved margins. Of these, 112 patients underwent a secondary surgery and 28 had residual disease (25%). No clinicopathological factor was correlated with presence of residual cancer. Also, bigger tumor size (p < 0.001) and the presence of in situ component (p < 0.001) were associated with positive margin and hence the need for a re-excision surgery. These results revealed that the significant rate of residual disease in the specimens of the secondary surgery indicates that a re-operation (either re-excision or simple mastectomy) cannot be omitted after obtaining a positive margin from the primary quadrantectomy.


Coagulation and fibrinolytic responses to exercise and cold exposure.
This study examined the effect of acute cold exposure on coagulation (PTT) and fibrinolysis (ELT), and the effect of cooling on subsequent exercise-induced coagulation and fibrinolytic responses. Ten male volunteers were tested at 5 degrees C and 28 degrees C on alternate days. Each subject began by sitting quietly for 60 min. Each then exercised on a cycle ergometer at 50 W for 5 min followed by 150 W for 10 min. Venous blood samples were taken before rest, after rest, and after exercise for each temperature on each of the two days. PTT, ELT, and hematocrit (HCT) were determined at each interval. Rectal temperature (Tre) and mean skin temperature (Tsk) were assessed at 15-min intervals throughout. Tsk was stable under neutral conditions but declined rapidly in the cold environment. Tre response was more complex but was significantly different for one contrast only (CE less than NE). ELT was shortened to 74, 62, and 44% while HCT increased to 107, 107, and 111% of pretest values for CR, NE, and CE, respectively. No significant change was noted for PTT. It is concluded that acute cold exposure as well as exercise stress results in an increase in ELT activity of blood; simultaneous enhancement of the coagulation status of the blood in response to stress is not inextricably linked to an elevation of fibrinolytic activity, a result that questions the importance of the Hageman factor dependent pathway between coagulation and fibrinolysis.


Disease-causing mutation in α-actinin-4 promotes podocyte detachment through maladaptation to periodic stretch.
α-Actinin-4 (ACTN4) bundles and cross-links actin filaments to confer mechanical resilience to the reconstituted actin network. How this resilience is built and dynamically regulated in the podocyte, and the cause of its failure in ACTN4 mutation-associated focal segmental glomerulosclerosis (FSGS), remains poorly defined. Using primary podocytes isolated from wild-type (WT) and FSGS-causing point mutant Actn4 knockin mice, we report responses to periodic stretch. While WT cells largely maintained their F-actin cytoskeleton and contraction, mutant cells developed extensive and irrecoverable reductions in these same properties. This difference was attributable to both actin material changes and a more spatially correlated intracellular stress in mutant cells. When stretched cells were further challenged using a cell adhesion assay, mutant cells were more likely to detach. Together, these data suggest a mechanism for mutant podocyte dysfunction and loss in FSGS-it is a direct consequence of mechanical responses of a cytoskeleton that is brittle.


SUV-quantification of physiological lung tissue in an integrated PET/MR-system: Impact of lung density and bone tissue.
The aim of the study was to investigate the influence of lung density changes as well as bone proximity on the attenuation correction of lung standardized uptake values (SUVs). 15 patients with mostly oncologic diseases were examined in 18F-FDG-PET/CT and subsequently in a fully integrated PET/MR scanner. From each PET dataset acquired in PET/MR, four different PET reconstructions were computed using different attenuation maps (μ-maps): i) CT-based μ-map (gold standard); ii) CT-based μ-map in which the linear attenuation coefficients (LAC) of the lung tissue was replaced by the lung LAC from the MR-based segmentation method; iii) based on reconstruction ii), the LAC of bone structures was additionally replaced with the LAC from the MR-based segmentation method; iv) the vendor-provided MR-based μ-map (segmentation-based method). Those steps were performed using MATLAB. CT Hounsfield units (HU) and SUVmean was acquired in different levels and regions of the lung. Relative differences between the differently corrected PETs were computed. Compared to the gold standard, reconstruction ii), iii) and iv) led to a relative underestimation of SUV in the posterior regions of -9.0%, -13.4% and -14.0%, respectively. Anterior and middle regions were less affected with an overestimation of about 6-8% in reconstructions ii)-iv). It could be shown that both, differences in lung density and the vicinity of bone tissue in the μ-map may have an influence on SUV, mostly affecting the posterior lung regions.


Biochemical and histological changes produced by sweeteners and cytarabine in the brain of young rats.
The aim of this study was to evaluate the effect of splenda and stevia on dopamine and 5-HIAA levels, and some biomarkers of oxidative stress in the presence of cytarabine. Forty-eight young male Wistar rats each with a weight of 80 g (four weeks of age), distributed in six groups of eight animals each, were treated as follows: group 1, control (NaCl 0.9% vehicle); group 2, cytarabine (0.6 g/kg); group 3, stevia (0.6 g/kg); group 4, cytarabine + stevia; group 5, splenda; and group 6, cytarabine + splenda. Cytarabine was given intravenously (IV) while stevia and splenda were administered orally for five days, using orogastric tube. At the end of treatment, the animals were sacrificed and glucose levels in blood were measured. The brains were dissected for histological analysis and homogenated to measure levels of dopamine, lipid peroxidation (TBARS), serotonin metabolite (5-HIAA), Na+, K+ ATPase activity, and glutathione (GSH), using validated methods. Sweeteners increased the glucose in animals that received cytarabine. Dopamine increased in cortex and decreased in striatum of animals that received stevia alone and combined with cytarabine. 5-HIAA decreased in striatum and cerebellum/medulla oblongata of animals that received sweeteners and cytarabine alone or combined. GSH increased in animals that received sweeteners and decreased with cytarabine. Lipoperoxidation decreased in groups that received sweeteners and cytarabine. Histopathological changes revealed marked degeneration of neuronal cells in animals treated with cytarabine. These results show that sweeteners as stevia or splenda may lead to the onset of unfavorable changes in dopamine and 5-HIAA. Antioxidant effects may be involved. Besides, histological changes revealed marked lesions of neuronal cells in experimental animals treated with cytarabine.


Rapid molecular detection of CMY-2, and CTX-M group 1 and 9 variants via recombinase polymerase amplification.
Due to their prevalence worldwide, the β-lactamases CTX-M and plasmid-mediated CMY-2 are important antimicrobial resistance enzymes in a clinical setting. While culture- and PCR-based detection methods exist for these targets, they are time consuming and require specialist equipment and trained personnel to carry out. In this study, three rapid diagnostic single-plex and a prototype triplex assay were developed, using recombinase polymerase amplification with lateral flow detection (RPA-LF), and tested for their sensitivity and specificity using two isolate DNA panels (n = 90 and n = 120 isolates). In addition, the RPA-LF assays were also tested with a small number of faecal extract samples (n = 18). The RPA-LF assays were able to detect bla CXT-M-group-1, bla CTX-M-group-9 and bla CMY-2-type variants with high sensitivity (82.1%-100%) and specificity (100%) within a short turnaround time (15-20 min for amplification and detection). RPA-LF assays developed in this study have the potential to be used at or close to the point of care, as well as in low-resource settings, producing rapid results to support healthcare professionals in their treatment decisions.


Stress Causing Factors Among Teachers in Elementary Schools and Their Relationship with Demographic and Job Characteristics.
Once high levels of work-related stress among teachers were confirmed many studies concentrated on identifying and investigating key stress factors among school teachers. Unfortunately there are very few researches made on stress causing factors among teachers in Republic of Macedonia. To determine the most frequent stress causing factors among teachers in elementary schools and to investigate their relationship with demographic and job characteristics. We performed a descriptive-analytical model of a cross-sectional study which involved 300 teachers employed in nine elementary schools. Evaluation of examined subjects included completion of a specially designed questionnaire. Among six categories of factors that generate work related stress (job demands, control, relationships, role, changes and support) control and support had the highest mean scores. Within the control category the highest levels of perceived teacher's work-related stress were caused by the following factors - changes in terms and conditions without consultation and given responsibility without the authority to take decisions. 141 out of the interviewed teachers (47%) have mentioned changes in terms and conditions without consultation as very stressful, while another 50 (16.67%) have reported it as stressful. 123 out of interviewed teachers (41%) have stated given responsibility without the authority to take decisions as very stressful, with another 105 (35%) have reported it as stressful. In the category support the highest levels of perceived teacher's work-related stress were caused by stress factors - lack of funds/resources to do the job and limited or no access to training. Out of 300 interviewed teachers, 179 (59.67%) have reported lack of funds/resources to do the job as very stressful, while another 50 (16.67%) as stressful. There is no significant relationship between the stress factor limited or no access to training and demographic and job characteristics. Our findings confirm that within the control category, the highest levels of perceived teacher's work-related stress were caused by changes in terms and conditions without consultation and given responsibility without the authority to take decisions, while in the category support, the same was true for stress factors lack of funds/resources to do the job and limited or no access to training. We have also concluded that the lower-grade school teachers, female teachers, teachers for whom this is the first job and teachers with university education perceive more often the lack of authority to take decisions as a very stressful factor than the upper-grade school teachers, male teachers, teachers previously employed in another workplace, and those with high education. The lower-grade school teachers, older teachers and teachers with university education perceive more often changes in education as a very stressful factor than the upper grade school teachers, younger teachers and those with high education.


Multiple immunizations. Ouch!
The purpose of this study was to determine the stated willingness of parents/caretakers to allow the administration of multiple, injected immunizations to their children at a single visit. Two hundred eighty-one parents/caretakers accompanying their children to an inner-city pediatric clinic were presented with hypothetical situations in which their children would be due for two, three, or four injections to complete their series of age-appropriate immunizations. Given a scenario of two needed injections, 24 (8.5%) of the 281 parents/caretakers preferred to divide the injections between two visits; for three injections, 119 (42.3%) preferred two visits; and for four injections, 164 (58.4%) preferred two visits. The commonly stated preference of our predominantly minority parent/caretaker population to divide more than two injections between two visits seriously conflicts with the US Public Health Service's National Vaccine Advisory Committee's recommendations and potentially exacerbates immunization delays. Therefore, physicians must be prepared to strongly urge simultaneous administration of all needed vaccine doses at any opportunity.


Assessment of forearm pronation strength in C6 and C7 radiculopathies.
Consecutive case series of patients with C6 and C7 radiculopathies. To explore the clinical utility and reliability of manual muscle testing of forearm pronation strength in C6 and C7 radiculopathies. EMG evidence of denervation of the pronator teres was the most common finding in C6 radiculopathies, and frequently present in C7 radiculopathies. Clinical evaluation of the pronator teres through manual muscle testing of forearm pronation has never been explored; therefore, its clinical utility is unknown as compared with the muscle groups that are traditionally evaluated. Fifty-five subjects with diagnostic imaging evidence of either C6 (n = 25) or C7 (n = 30) cervical root compression and clinical symptoms consistent with cervical radiculopathy were recruited for this study. These subjects underwent manual muscle testing of forearm pronation, wrist extension, elbow flexion, and elbow extension. The frequency of impaired strength was recorded and compared for C6 and C7 radiculopathies. A second examiner evaluated each subject, with his or her findings compared with the first examiner only for the determination of interrater reliability. In C6 radiculopathy subjects, forearm pronation weakness was present in 72%, was twice as common as wrist extension weakness, was present in all cases where elbow flexion or wrist extension weakness was noted, and was found in all but 2 subjects where elbow extension weakness was present. In C7 radiculopathy subjects, forearm pronation weakness accompanies elbow extension weakness in 23% of subjects and was the only weakness in 10% of subjects. Manual muscle testing demonstrated adequate interrater reliability. Forearm pronation weakness is the most frequent motor finding in C6 radiculopathies and may be noted is some cases of C7 nerve root compression.


Anesthetic Management of the Patient with Mitochondrial Disease: A Review of Current Best Evidence.
Anesthetic management of the patient with mitochondrial disease (MD) requires thoughtful preoperative planning and hypervigilant perioperative monitoring. MD affects 1 in 4,000 persons and is often an unfamiliar topic to the anesthesia provider. This review aims to inform the anesthetist on important considerations in perioperative management of MD. Patients with MD have impaired mitochondrial energy formation pathways affecting function of cardiac, central nervous, and musculoskeletal systems. All general anesthetics interfere with these mitochondrial bioenergetic pathways. MD patients exhibit hypersensitivity to volatile anesthetics. Propofol interferes with mitochondrial function via multiple pathways thus its use should be limited. MD is not at increased risk for malignant hyperthermia and should not be managed with prolonged propofol infusion. Succinylcholine is contraindicated due to hyperkalemia and myotonic risks. Nondepolarizing agents should be used with caution given unpredictable effects. No single anesthetic plan has been found to be safer than another in patients with MD. Intravenous and volatile anesthetics should be titrated incrementally while monitoring anesthetic depth clinically or via processed electroencephalogram (EEG). All MD patients should be optimized by minimizing fasting times, careful fluid selection to avoid lactate, and hypervigilant temperature management aimed at reducing the detrimental effects of catabolic stress during the perioperative period.


Adaptive Fuzzy Control With High-Order Barrier Lyapunov Functions for High-Order Uncertain Nonlinear Systems With Full-State Constraints.
This paper focuses on the practical output tracking control for a category of high-order uncertain nonlinear systems with full-state constraints. A high-order tan-type barrier Lyapunov function (BLF) is constructed to handle the full-state constraints of the control systems. By the BLF and combining a backstepping design technique, an adding a power integrator, and a fuzzy control, the proposed approach can control high-order uncertain nonlinear system with full-state constraints. A novel controller is designed to ensure that the tracking errors approach to an arbitrarily small neighborhood of zero, and the constraints on system states are not violated. The numerical example demonstrates effectiveness of the proposed control method.


Weathering and Chemical Degradation of Methyl Eugenol and Raspberry Ketone Solid Dispensers for Detection, Monitoring, and Male Annihilation of Bactrocera dorsalis and Bactrocera cucurbitae (Diptera: Tephritidae) in Hawaii.
Solid male lure dispensers containing methyl eugenol (ME) and raspberry ketone (RK), or mixtures of the lures (ME + RK), and dimethyl dichloro-vinyl phosphate (DDVP) were evaluated in area-wide pest management bucket or Jackson traps in commercial papaya (Carica papaya L.) orchards where both oriental fruit fly, Bactrocera dorsalis (Hendel), and melon fly, Bactrocera cucurbitae (Coquillett), are pests. Captures of B. dorsalis with fresh wafers in Jackson and bucket traps were significantly higher on the basis of ME concentration (Mallet ME [56%] > Mallet MR [31.2%] > Mallet MC [23.1%]). Captures of B. cucurbitae with fresh wafers in Jackson and bucket traps were not different regardless of concentration of RK (Mallet BR [20.1%] = Mallet MR [18.3%] = Mallet MC [15.9%]). Captures of B. dorsalis with fresh wafers, compared with weathered wafers, were significantly different after week 12; captures of B. cucurbitae were not significantly different after 16 wk. Chemical analyses revealed presence of RK in dispensers in constant amounts throughout the 16-wk trial. Degradation of both ME and DDVP over time was predicted with a high level of confidence by nonlinear asymptotic exponential decay curves. Results provide supportive data to deploy solid ME and RK wafers (with DDVP) in fruit fly traps for detection programs, as is the current practice with solid TML dispensers placed in Jackson traps. Wafers with ME and RK might be used in place of two separate traps for detection of both ME and RK responding fruit flies and could potentially reduce cost of materials and labor by 50%.


Population cycles: generalities, exceptions and remaining mysteries.
Population cycles are one of nature's great mysteries. For almost a hundred years, innumerable studies have probed the causes of cyclic dynamics in snowshoe hares, voles and lemmings, forest Lepidoptera and grouse. Even though cyclic species have very different life histories, similarities in mechanisms related to their dynamics are apparent. In addition to high reproductive rates and density-related mortality from predators, pathogens or parasitoids, other characteristics include transgenerational reduced reproduction and dispersal with increasing-peak densities, and genetic similarity among populations. Experiments to stop cyclic dynamics and comparisons of cyclic and noncyclic populations provide some understanding but both reproduction and mortality must be considered. What determines variation in amplitude and periodicity of population outbreaks remains a mystery.


Recent studies on perfluorochemical (PFC) emulsion as an oxygen carrier in Japan.
In summary, we have discussed PFC emulsions as oxygen carriers, and concluded as follows: PFC emulsions which are clinically usable at present, such as Fluosol-DA, have some negative points. For instance, there is the requirement of relatively high FiO2 level, short retention time in the blood stream, slow excretion rate from the organs, limited dosage for infusion, and so on. However, in the clinical cases of moderate acute anemia, the consumed oxygen in the PFC phase was nearly 30% of that in the hemoglobin phase in the administration of only 1,000 ml of Fluosol-DA. It strongly suggests that PFC emulsion can carry a considerable amount of oxygen to the tissues and play an important role in improving the tissue hypoxia. Moreover, we surgeons wish to say that there is a great difference for the surgeons' mental state during a surgical operation between the cases where no blood transfusion is allowed for a religious or other reason, and the cases where we may use Fluosol-DA depending on the patients' condition. In the former cases, surgeons will be under stress such that he or she might cause the patients to lose blood excessively. On the other hand, when the surgeon has something in reserve, that is, when he or she may use Fluosol-DA if needed, a good result will usually be obtained in the operation, even without actually using Fluosol-DA. One might be led to say that a key point for the success of operations is the surgeon's mental condition, freedom from anxiety.(ABSTRACT TRUNCATED AT 250 WORDS)


Capital femoral epiphysis and growth plate of the asymptomatic hip joint in unilateral Perthes disease.
Radiograms of 173 children with unilateral Perthes disease were reviewed with particular reference to the presence of flattening and irregularity of the 'unaffected' epiphyses. The slope and shape of the growth plate were also evaluated. About 35% of children with Perthes disease showed changes of the unaffected proximal femur in the first radiograms of the hip joints. These consisted of small epiphysis, flattening of the epiphysis, contour irregularities (20%), and changes in the growth plate (15%). The radiographic abnormalities were not accompanied by any clinical symptoms of the asymptomatic hip joint and they receded with age during treatment.


Clinical coding of prospectively identified paediatric adverse drug reactions--a retrospective review of patient records.
National Health Service (NHS) hospitals in the UK use a system of coding for patient episodes. The coding system used is the International Classification of Disease (ICD-10). There are ICD-10 codes which may be associated with adverse drug reactions (ADRs) and there is a possibility of using these codes for ADR surveillance. This study aimed to determine whether ADRs prospectively identified in children admitted to a paediatric hospital were coded appropriately using ICD-10. The electronic admission abstract for each patient with at least one ADR was reviewed. A record was made of whether the ADR(s) had been coded using ICD-10. Of 241 ADRs, 76 (31.5%) were coded using at least one ICD-10 ADR code. Of the oncology ADRs, 70/115 (61%) were coded using an ICD-10 ADR code compared with 6/126 (4.8%) non-oncology ADRs (difference in proportions 56%, 95% CI 46.2% to 65.8%; p < 0.001). The majority of ADRs detected in a prospective study at a paediatric centre would not have been identified if the study had relied on ICD-10 codes as a single means of detection. Data derived from administrative healthcare databases are not reliable for identifying ADRs by themselves, but may complement other methods of detection.


A combined fuzzy backtracking search optimization algorithm to localize retinal blood vessels for diabetic retinopathy.
For diabetic retinopathy (DR) surgery, localization of retinal blood vessels is of paramount importance. Fundus images which are often used for DR diagnosis suffer from poor contrast (between the retinal background and the blood vessels, due to its size) limits the diagnosis. In addition to this, various pathological changes in retinal blood vessels may also be observed for different diseases such as glaucoma and diabetes. To alleviate, in this paper, an automated unsupervised retinal blood vessel segmentation technique, based on backtracking search optimization algorithm (BSA), is proposed. The BSA method is used to optimize the local search of fuzzy c-means clustering (FCM) algorithm to find micro-diameter sized vessels along with coarse vessels. The proposed technique is tested on two publicly available retinal datasets (i.e., STARE and DRIVE) and verified using the dataset collected from various hospitals in Bangalore and Mangalore, India. The results show that the performance of the proposed method is comparable to the conventional techniques in terms of sensitivity, specificity, and accuracy.


The Distinction of Amyloid-β Protein Precursor (AβPP) Ratio in Platelet Between Alzheimer's Disease Patients and Controls: A Systematic Review and Meta-Analysis.
To systematically assess the clinical significance of platelet amyloid-β protein precursor (AβPP) ratio between Alzheimer's disease (AD) patients and controls. 14 articles were selected in this analysis by search of databases including PubMed and Web of Science up to December 2016. Random effects models were used to calculate the standardized mean difference (SMD). Subgroup analyses were used to detect the cause of heterogeneity. The result showed a significant drop in platelet AβPP ratio in AD patients compared to controls [SMD: -1.871; 95% CI: (-2.33, -1.41); p < 0.001; I2 = 88.0% ]. Subgroup analysis revealed races or the quality of studies may be the cause of high heterogeneity. This meta-analysis concluded that there is a close association between platelet AβPP ratio and AD. It is necessary to design a sizable sample study to further support that platelet AβPP ratio can be a biomarker of AD.


Getting started in research: systematic reviews and meta-analyses.
Systematic reviews are one of the major building blocks of evidence-based medicine. This overview is an introduction to conducting systematic reviews and meta-analyses. Systematic reviews and meta-analyses of randomised controlled trials (RCTs) represent the most robust form of design in the hierarchy of research evidence. In addition, primary data do not have to be collected by the researcher him/herself, and there is no need for approval from an ethics committee. Systematic reviews and meta-analyses are not as daunting as they may appear to be, provided the scope is sufficiently narrow and an appropriate supervisor available.


[Psychological treatment for obesity].
Obesity is a chronic disease. Current management is based in the modification of the lifestyle, mainly regarding to eating habits and physical activity. Eating habits are acquired during the childhood and kept through the entire life. Modification of any habit requires the use of specific psychological methods such as cognitive-behavioural therapy, which is based on first notions of learning theories. Very often, obese patients and therapist think that the obesity is a problem not related to other aspects of their lives. Thus the objective of the treatment is only weight loss, instead of looking for a modification of patient's behaviour. In the present review we try to update the treatment of obesity in adult patients mainly regarding to the psychological approach.


Staphylococcus aureus host specificity: comparative genomics of human versus animal isolates by multi-strain microarray.
Staphylococcus aureus is a commensal and pathogen of several mammalian species, particularly humans and cattle. We aimed to (i) identify S. aureus genes associated with host specificity, (ii) determine the relatedness of human and animal isolates, and (iii) identify whether human and animal isolates typically exchanged mobile genetic elements encoding virulence and resistance genes. Using a well-validated seven-strain S. aureus microarray, we compared 56 UK S. aureus isolates that caused infection in cows, horses, goats, sheep and a camel with 161 human S. aureus isolates from healthy carriers and community acquired infections in the UK. We had previously shown that human isolates are clustered into ten dominant and a few minor lineages, each with unique combinations of surface proteins predicted to bind to human proteins. We found that the animal-associated S. aureus clustered into ten lineages, with 61 % assigned to four lineages, ST151, ST771, ST130 and ST873, that were unique to animals. The majority of bovine mastitis was caused by isolates of lineage ST151, ST771 and ST97, but a few human lineages also caused mastitis. S. aureus isolated from horses were more likely to cluster into human-associated lineages, with 54 % of horse-associated S. aureus assigned to the human clusters CC1, CC8 and CC22; along with the presence of some multi-drug resistant strains, this suggests a human origin. This is the most comprehensive genetic comparison of human versus animal S. aureus isolates conducted, and because we used a whole-genome approach we could estimate the key genes with the greatest variability that are associated with host specificity. Several genes conserved in all human isolates were variable or missing in one or more animal lineages, including the well-characterized lineage specific genes fnbA, fnbB and coa. Interestingly, genes carried on mobile genetic elements (MGEs) such as chp, scn and sak were less common in animal S. aureus isolates, and bap was not found. There was a lot of MGE variation within lineages, and some evidence that exchange of MGEs such as bacteriophage and pathogenicity islands between animal and human lineages is feasible, but there was less evidence of antibiotic resistance gene transfer on the staphylococcal cassette chromosomes (SCC) or plasmids. Surprisingly, animal lineages are closely related to human lineages and only a handful of genes or gene combinations may be responsible for host specificity.


[Behavior of serum alpha 1-antitrypsin in chronic hepatopathies and its diagnostic significance].
The behaviour of alpha 1 antitrypsin in 76 subjects with cirrhosis of the liver, 14 subjects with chronic persistent hepatitis, 14 subjects with chronic active hepatitis, 8 subjects with toxic hepatitis, 5 subjects with obstructive jaundice, 5 subjects with liver carcinoma. 4 of these groups (cirrhosis, chronic active hepatitis, obstructive jaundice, hepatoma) showed alpha 1 antitrypsin blood levels significantly higher than the control group (82 healthy subjects). Very high alpha 1 antitrypsin blood levels, significantly greater than in cirrhosis, were found in the patients with hepatoma. All these subjects also showed blood levels of alpha fetoprotein higher than 100 ng/ml. The diagnostic meaning of these finding was considered.


Hypoxia and B cells.
The ability of cells to sense and adapt to changes in oxygen is mediated by hypoxia-inducible factor (HIF). Immune cells function in physiologically complex and varying environments whereby oxygen, pH, nutrients, metabolites and cytokines are continuously fluctuating. HIF is well known to play an important role in coordinating the adaptation and function of both innate immune cells and T cells in these complex environments. This review summarises recent discoveries concerning how hypoxia and HIF control B cell behaviour, and regulate antibody quality and decisions concerning tolerance. Hypoxia and HIF activation may provide an important context; coordinating metabolism with variable demands for quiescence, rapid proliferation, and differentiation. Understanding when and how HIF is activated during B cell development and response is important as drugs targeting HIF could influence antibody responses, providing novel therapeutic opportunities for vaccine adjuvants and in treating autoimmunity.


Spt5 Plays Vital Roles in the Control of Sense and Antisense Transcription Elongation.
Spt5 is an essential and conserved factor that functions in transcription and co-transcriptional processes. However, many aspects of the requirement for Spt5 in transcription are poorly understood. We have analyzed the consequences of Spt5 depletion in Schizosaccharomyces pombe using four genome-wide approaches. Our results demonstrate that Spt5 is crucial for a normal rate of RNA synthesis and distribution of RNAPII over transcription units. In the absence of Spt5, RNAPII localization changes dramatically, with reduced levels and a relative accumulation over the first ∼500 bp, suggesting that Spt5 is required for transcription past a barrier. Spt5 depletion also results in widespread antisense transcription initiating within this barrier region. Deletions of this region alter the distribution of RNAPII on the sense strand, suggesting that the barrier observed after Spt5 depletion is normally a site at which Spt5 stimulates elongation. Our results reveal a global requirement for Spt5 in transcription elongation.