Transplantation of a fetus with paternal Thy-1(+)CD34(+)cells for chronic granulomatous disease.
A fetus diagnosed with X-linked chronic granulomatous disease was transplanted with Thy-1(+)CD34(+) cells of paternal origin. The transplant was performed at 14 weeks gestation by ultrasound guided injection into the peritoneal cavity. The fetus was delivered at 38 weeks gestation after an otherwise uneventful pregnancy. Umbilical cord blood was collected and used to determine the level of peripheral blood chimerism as well as levels of functional engrafted cells. Flow cytometry was used to detect donor leukocytes identified as HLA-A2(-)B7(+) cells, whereas recipient cells were identified as HLA-A2(+)B7(-) cells. No evidence of donor cell engraftment above a level of 0.01% was found. PCR was used to detect HLA-DRB1*15(+) donor cells among the recipient's HLA-DRB1*15(-) cells, but no engraftment was seen with a sensitivity of 1:1000. The presence of functional, donor-derived neutrophils was assessed by flow cytometry using two different fluorescent dyes that measure reactive oxygen species generated by the phagocyte NADPH oxidase. No evidence of paternal-derived functional neutrophils above a level of 0.15% was observed. Peripheral blood and bone marrow samples were collected at 6 months of age. Neither sample showed engraftment by HLA typing using both flow cytometry and PCR. Functional phagocytes were also not observed. Furthermore, no indication of immunological tolerance specific for the donor cells was indicated by a mixed lymphocyte reaction assay performed at 6 months of age. While there appears to be no engraftment of the donor stem cells, the transplant caused no harm to the fetus and the child was healthy at 6 months of age. Analyses of fetal tissues, obtained from elective abortions, revealed that CD3(+) T cells and CD56(+)CD3(-) NK cells are present in the liver at 8 weeks gestation and in the blood by 9 weeks gestation. The presence of these lymphocytes may contribute to the lack of donor cell engraftment in the human fetus.


A retrospective study comparing percutaneous and open pedicle screw fixation for thoracolumbar fractures with spinal injuries.
The purpose of this study was to evaluate the effectiveness between percutaneous and open pedicle screw fixation for treating thoracolumbar fractures with spinal injuries. A total of 105 patients with thoracolumbar fractures and spinal injuries were divided into a percutaneous pedicle screw fixation (PPSF) group with 56 patients, who underwent percutaneous pedicle screw fixation, and an open pedicle screw fixation (OPSF) group with 49 patients, who underwent open pedicle screw fixation in accordance with the treatment project. Relative operation indexes, radiologic, and effectiveness parameters were assessed and compared between the 2 groups. Demographic and clinical features including age, body mass index, gender, fracture level, fracture classification, and Frankel grade in both groups were not significantly different (all P >.05). The PPSF group exhibits significantly lower operation time, intraoperative blood loss, postoperative drainage volume, and hospital stay on average compared with the OPSF group (all P < .05). Besides, the average postoperative radiologic parameters, including Cobb angle (CA), vertebral wedge angle (VWA), vertebral front height percentage (VFHP), and sagittal index (SI), in both the groups were not significantly different (all P > .05). Nevertheless, both visual analogue scale (VAS) and Oswestry disability index (ODI) after surgery decreased more substantially in the PPSF group than in the OPSF group (all P < .05) while no significant difference in VAS scores or ODI during the last follow-up period was demonstrated in both the groups (both P > .05). Frankel classifications were stimulated in both the groups during the last follow-up period. PPSF has a smaller incision, less intraoperative blood loss, shorter recovery time, higher safety measures on average compared with OPSF with respect to managing thoracolumbar fractures with spinal injuries.


[Experiences fo three year's routine operation of an anesthesia information management system (AIMS) at a university clinic in Giessin].
In 1994, the Department of Anaesthesiology and Intensive Care Medicine of the Justus Liebig University at Giessen decided to install an Anaesthesia Information Management System (AIMS). Individual aspects and results from routine operation are presented, demonstrating the quality of the documentation and the value of information at the anaesthesiological workstation. The paper discusses which adaptations are necessary according to the experience gathered. For the installation of the system Apple Macintosh Clients (Apple Computer, Inc., Cupertino, California) and a File Server were integrated into the partially existing hospital network. The hospital network had to be enlarged during the project according to the Anaesthesiological requirements. The software of the Hospital Information System (HIS) and an HTML browser were installed at individual workstation computers in addition to the Anaesthesia documentation software NarkoData (ProLogic GmbH, Erkrath). The remote control software Timbuktu (Farallon, Alameda, USA) has been added to facilitate remote administration. The file administration programme FileWave (Wave Research, Berkeley, USA) is used for file distribution. Since 1995, all anaesthesia procedures have been documented with the system, either by online or postoperative recording. Since 1997, the recorded information has been stored in a relational Oracle 7 data bank (Oracle Corporation). From 1995 to 1997, 60,405 anaesthesiological procedures have been recorded with the help of this AIMS at 111 decentralised workstations. In 1997, 87.8% of the 21,130 performed anaesthesia procedures have been recorded online with the system and 12.2% postoperatively. From 1995 to 1997, the number of recorded procedures increased by 6.4% from 19,854 to 21,130. Because of lacking interfaces at some patient monitoring stations, the automatic recording of patient data could only be implemented at 69 workstations (62%). With the corresponding access rights, important patient information from the HIS (diagnoses, laboratory results, etc.), records of previous Anaesthesia procedures, numerous statistics, and the whole information from the hospital's intranet (including e-mail) are available at the anaesthesiological workstation at any time. The implementation of the AIMS and an effective user support have been able to increase significantly the quality of documentation, the flow of information at the anaesthesia workplace and the number of recorded Anaesthesia procedures. All recorded data can be analysed immediately The expansion of the automatic data transfer from the patient monitoring, interfaces to other computer subsystems of the hospital and a practicable evaluation programme are necessary for further enhancing the efficiency of the AIMS.


Trustworthiness appraisal deficits in borderline personality disorder are associated with prefrontal cortex, not amygdala, impairment.
Borderline Personality Disorder (BPD) is associated with sensitivity to signals of interpersonal threats and misplaced trust in others. The amygdala, an integral part of the threat evaluation and response network, responds to both fear- and trust-related stimuli in non-clinical samples, and is more sensitive to emotional stimuli in BPD compared to controls. However, it is unknown whether the amygdalar response can account for deficits of trust and elevated sensitivity to interpersonal threat in BPD. Facial stimuli were presented to 16 medication-free women with BPD and 17 demographically-matched healthy controls (total n = 33). Participants appraised fearfulness or trustworthiness of the stimuli while BOLD fMRI was obtained. Though BPD participants judged stimuli as less trustworthy compared to controls, trustworthiness did not correlate with amygdalar activity in either group. Trustworthiness correlated with prefrontal regional activity in the insula and lateral prefrontal cortex. Prefrontal BOLD activity while appraising trustworthiness was smaller in BPD compared to controls, and the size of the reduction was proportional to each participant's response bias. Neural substrates of trustworthiness appraisal are associated with the lateral prefrontal cortex and insula, not amygdala, suggesting that untrustworthy stimuli do not elicit a subcortical threat response. Current models of BPD and its treatment may need to include a focus on improving impairments in frontally mediated trustworthiness appraisal in addition to amygdala- driven emotional hyper-reactivity.


Reason Defaults: Presenting Defaults With Reasons for Choosing Each Option Helps Decision-Makers With Minority Interests.
Defaults are powerful tools for nudging individuals toward potentially beneficial options. However, defaults typically guide all decision-makers toward the same option and, consequently, may misguide individuals with minority interests. We test whether presenting defaults with information about heterogeneity can help individuals with minority interests select alternative options, and we dub this intervention a "reason default." Reason defaults preselect the option that is best for most individuals (like standard defaults) but also explain (a) why the default was selected and (b) who should opt for an alternative. In five preregistered studies using online convenience samples of adults (N = 4,210), we find that reason defaults can improve decision-makers' outcomes over standard defaults and forced choices by guiding most individuals toward the default option while helping individuals with minority interests select an alternative. Further, participants reported that reason defaults enhance transparency, decision ease, and understanding of the choice relative to standard defaults and forced choices.


MMP-responsive nanomaterials.
Matrix metalloproteinases (MMP) are enzymes that degrade the extracellular matrix and regulate essential normal cell behaviors. Inhibition of these enzymes has been a strategy for anti-cancer therapy since the 1990s, but with limited success. A new type of MMP-targeting strategy exploits the innate selective hydrolytic activity and consequent catalytic signal amplification of the proteinases, rather than inhibiting it. Using nanomaterials, the enzymatic chemical reaction can trigger the temporal and spatial activation of the anti-cancer effects, amplify the associated response, and cause mechanical damage or report on cancer cells. We analyzed nearly 60 literature studies that incorporate chemical design strategies that lead to spatial, temporal, and mechanical control of the anti-cancer effect through four modes of action: nanomaterial shrinkage, induced aggregation, formation of cytotoxic nanofibers, and activation by de-PEGylation. From the literature analysis, we derived chemical design guidelines to control and enhance MMP activation of nanomaterials of various chemical compositions (peptide, lipid, polymer, inorganic). Finally, the review includes a guide on how multiple characteristics of the nanomaterial, such as substrate modification, supramolecular structure, and electrostatic charge should be collectively considered for the targeted MMP to result in optimal kinetics of enzyme action on the nanomaterial, which allow access to amplification and additional levels of spatial, temporal, and mechanical control of the response. Although this review focuses on the design strategies of MMP-responsive nanomaterials in cancer applications, these guidelines are expected to be generalizable to systems that target MMP for treatment or detection of cancer and other diseases, as well as other enzyme-responsive nanomaterials.


Diagnosis and treatment of pancreatic duct disruption or disconnection: an international expert survey and case vignette study.
Pancreatic duct disruption or disconnection is a potentially severe complication of necrotizing pancreatitis. With no existing treatment guidelines, it is unclear whether there is any consensus among experts in clinical practice. We evaluated current expert opinion regarding the diagnosis and treatment of pancreatic duct disruption and disconnection in an international case vignette study. An online case vignette survey was sent to 110 international expert pancreatologists. Expert selection was based on publications in the last 5 years and/or participation in development of IAP/APA and ESGE guidelines on acute pancreatitis. Consensus was defined as agreement by at least 75% of the experts. The response rate was 51% (n = 56). Forty-four experts (79%) obtained a MRI/MRCP and 52 experts (93%) measured amylase levels in percutaneous drain fluid to evaluate pancreatic duct integrity. The majority of experts favored endoscopic transluminal drainage for infected (peri)pancreatic necrosis and pancreatic duct disruption (84%, n = 45) or disconnection (88%, n = 43). Consensus was lacking regarding the treatment of patients with persistent percutaneous drain production, and with persistent sterile necrosis. This international survey of experts demonstrates that there are many areas for which no consensus existed, providing clear focus for future investigation.


Glucagon-like peptide-2 induces rapid digestive adaptation following intestinal resection in preterm neonates.
Short bowel syndrome (SBS) is a frequent complication after intestinal resection in infants suffering from intestinal disease. We tested whether treatment with the intestinotrophic hormone glucagon-like peptide-2 (GLP-2) increases intestinal volume and function in the period immediately following intestinal resection in preterm pigs. Preterm pigs were fed enterally for 48 h before undergoing resection of 50% of the small intestine and establishment of a jejunostomy. Following resection, pigs were maintained on total parenteral nutrition (TPN) without (SBS, n = 8) or with GLP-2 treatment (3.5 μg/kg body wt per h, SBS+GLP-2, n = 7) and compared with a group of unresected preterm pigs (control, n = 5). After 5 days of TPN, all piglets were fed enterally for 24 h, and a nutrient balance study was performed. Intestinal resection was associated with markedly reduced endogenous GLP-2 levels. GLP-2 increased the relative absorption of wet weight (46 vs. 22%), energy (79 vs. 64%), and all macronutrients (all parameters P < 0.05). These findings were supported by a 200% increase in sucrase and maltase activities, a 50% increase in small intestinal epithelial volume (P < 0.05), as well as increased DNA and protein contents and increased total protein synthesis rate in SBS+GLP-2 vs. SBS pigs (+100%, P < 0.05). Following intestinal resection in preterm pigs, GLP-2 induced structural and functional adaptation, resulting in a higher relative absorption of fluid and macronutrients. GLP-2 treatment may be a promising therapy to enhance intestinal adaptation and improve digestive function in preterm infants with jejunostomy following intestinal resection.


A polymer optoelectronic interface provides visual cues to a blind retina.
A polymer bulk heterojunction structure utilized as an active photosensitive platform to evoke neuronal activity in a blind retina. The features of the elicited action potentials correlate with the optoelectronic properties of the polymer/electrolyte interface, and resembles the natural response of the retina to light. The polymer interface can be used as an optoelectronic epiretinal interface for retinal prosthesis with no requirement for external power sources or connection cables.


Cyanobacteria blooms: effects on aquatic ecosystems.
Cyanobacteria become increasingly dominant as concentrations of TP and TN increase during eutrophication of lakes, rivers and estuaries. Temporal dynamics of cyanobacteria blooms are variable--in some systems persistent blooms occur in summer to fall, whereas in other systems blooms are more sporadic. Cyanobacteria blooms have a wide range of possible biological impacts including potential toxic effects on other algae, invertebrates and fish, impacts to plants and benthic algae due to shading, and impacts to food web function as large inedible algae produce a bottleneck to C and energy flow in the plankton food web. In lakes with dense blooms of cyanobacteria, accumulation of organic material in lake sediments and increased bacterial activity also may lead to anoxic conditions that alter the structure of benthic macro-invertebrates. Diffusive internal P loading may increase, and hypolimnetic anoxia may lead to a loss of piscivorous fish that require a summer cold water refuge in temperate lakes. Ecosystem changes associated with frequent blooms may result in delayed response of lakes, rivers and estuaries to external nutrient load reduction. Despite numerous case studies and a vast literature on species-specific responses, community level effects of cyanobacterial blooms are not well understood--in particular the realized impacts of toxins and changes in food web structure/function. These areas require additional research given the prevalence of toxic blooms in the nation's lakes, rivers and coastal waters--systems that provide a wide range of valued ecosystem services.


Single Primer Enrichment Technology (SPET) for High-Throughput Genotyping in Tomato and Eggplant Germplasm.
Single primer enrichment technology (SPET) is a new, robust, and customizable solution for targeted genotyping. Unlike genotyping by sequencing (GBS), and like DNA chips, SPET is a targeted genotyping technology, relying on the sequencing of a region flanking a primer. Its reliance on single primers, rather than on primer pairs, greatly simplifies panel design, and allows higher levels of multiplexing than PCR-based genotyping. Thanks to the sequencing of the regions surrounding the target SNP, SPET allows the discovery of thousands of closely linked, novel SNPs. In order to assess the potential of SPET for high-throughput genotyping in plants, a panel comprising 5k target SNPs, designed both on coding regions and introns/UTRs, was developed for tomato and eggplant. Genotyping of two panels composed of 400 tomato and 422 eggplant accessions, comprising both domesticated material and wild relatives, generated a total of 12,002 and 30,731 high confidence SNPs, respectively, which comprised both target and novel SNPs in an approximate ratio of 1:1.6, and 1:5.5 in tomato and eggplant, respectively. The vast majority of the markers was transferrable to related species that diverged up to 3.4 million years ago (Solanum pennellii for tomato and S. macrocarpon for eggplant). Maximum Likelihood phylogenetic trees and PCA outputs obtained from the whole dataset highlighted genetic relationships among accessions and species which were congruent with what was previously reported in literature. Better discrimination among domesticated accessions was achieved by using the target SNPs, while better discrimination among wild species was achieved using the whole SNP dataset. Our results reveal that SPET genotyping is a robust, high-throughput technology for genetic fingerprinting, with a high degree of cross-transferability between crops and their cultivated and wild relatives, and allows identification of duplicates and mislabeled accessions in genebanks.


[Functional organization of local neuronal networks in the cat neocortex. Dependence on the food motivation].
The multiple unit activity (MUA) from clusters of adjacent neurones in deep layers of the frontal and motor cortex was recorded in alert cats with different levels of alimentary motivation. Up to 7 spike trains were selected from the MUA. Neurones in the local circuits could be divided into 2 groups: large neurones with prevailing divergent characteristics, and small neurones with prevailing convergent characteristics. A 24-hour food deprivation altered the cross-correlation interneuronal connections with a time delay within the range of 2 to 100 ms.


Copper transport in rats involving a new plasma protein.
The time course of distribution of high-specific activity 67CuCl2 to tissues and plasma components was followed in adult, female rats. Immediately after intubation or injection, tracer 67Cu associated with two components of the blood plasma separable on columns of Sephadex G-150: albumin and another (larger) component, which was not ceruloplasmin. The latter, tentatively named transcuprein, had an apparent molecular weight of 270,000 and a high affinity for Cu2+, as judged by processing through Chelex-100, dilution, and exchange with albumin copper, in vitro and in vivo. It was capable of donating copper to tumor cells in serum-free medium. Analysis of "cold" plasma by furnace atomic absorption confirmed the presence of 10-15% of plasma copper in this peak. Plots of percent dose and 67Cu specific activity against time showed that copper followed a very specific pathway after binding to albumin and transcuprein, entering mainly the liver, then reappearing in the plasma on ceruloplasmin, and then achieving peak distribution in peripheral tissues (muscles, brain, etc.). 67Cu disappeared from liver and kidney with an apparent half-life of 4.5 days, the same exponential rate found for whole body turnover. Apparent turnover of ceruloplasmin copper was more rapid. Even after 7-12 days, tracer copper in plasma was still found exclusively with ceruloplasmin. The results indicate that copper follows a carefully prescribed path, on entering the blood and binding to a new transport protein.


Vanadium Dioxide Circuits Emulate Neurological Disorders.
Information in the central nervous system (CNS) is conducted via electrical signals known as action potentials and is encoded in time. Several neurological disorders including depression, Attention Deficit Hyperactivity Disorder (ADHD), originate in faulty brain signaling frequencies. Here, we present a Hodgkin-Huxley model analog for a strongly correlated VO2 artificial neuron system that undergoes an electrically-driven insulator-metal transition. We demonstrate that tuning of the insulating phase resistance in VO2 threshold switch circuits can enable direct mimicry of neuronal origins of disorders in the CNS. The results introduce use of circuits based on quantum materials as complementary to model animal studies for neuroscience, especially when precise measurements of local electrical properties or competing parallel paths for conduction in complex neural circuits can be a challenge to identify onset of breakdown or diagnose early symptoms of disease.


DMPS as a rescue agent for the nephropathy induced by mercuric chloride.
The effectiveness of 2,3-dimercaptopropane-1-sulfonate (DMPS) as a rescue agent for the acute nephropathy induced by HgCl2 was studied in uninephrectomized (NPX) and sham-operated (SO) rats. NPX and SO rats that were given a toxic 2.5-mumol/kg dose of HgCl2 developed severe renal damage within 24 hr after the HgCl2 was administered. Renal injury was assessed by measuring plasma creatinine, creatinine clearance, fractional excretion of several biological markers, the rate of excretion of cellular enzymes and plasma solutes and severity of morphologically demonstrable necrosis in the pars recta of proximal tubules. When a 10-mg/kg dose of DMPS was given to the NPX and SO rats 1 hr after treatment with the 2.5-mumol/kg dose of HgCl2, the nephropathy induced by the dose of HgCl2 was less severe. Moreover, the NPX rats had significantly less severe renal damage than did the SO rats. Renal damage was completely absent from both NPX and SO rats that were given a 100-mg/kg dose of DMPS 1 hr after treatment with the 2.5-mumol/kg dose of HgCl2. These data indicate that at the 10-mg/kg dose of DMPS, NPX rats are protected against the nephrotoxic effects of a 2.5-mumol/kg dose of HgCl2 to a greater extent than are SO rats. Moreover, the data show that complete rescue from the 2.5-mumol/kg dose of HgCl2 is afforded to NPX and SO rats given 100 mg/kg of DMPS within 1 hr after treatment with HgCl2. This complete rescue is afforded for at least 24 hr. Based on the present findings DMPS may prove to be a useful rescue agent against the acute nephropathy induced by HgCl2.


Early menarche and blood pressure in adulthood: systematic review and meta-analysis.
It has been reported that early menarche is associated with high blood pressure and hypertension. However, some studies have failed to observe such association. We carried out a systematic review and meta-analysis on the association of early menarche with hypertension and high blood pressure in adulthood. PUBMED, SciELO, Scopus and LILACS databases were searched. Studies that evaluated the association of early menarche with hypertension or high blood pressure, among women aged 20 years or more were included. Random effects models were used to pool the estimates. Meta-regression was used to evaluate the contribution of different co-variables to heterogeneity. We identified 17 studies with 18 estimates on the association of early menarche with hypertension and high blood pressure. The odds of hypertension/high blood pressure was higher among women with early menarche [pooled (OR):1.25; 95% confidence interval (CI): 1.17-1.34; P < 0.001]. In the meta-regression analysis, studies evaluating 1500 subjects or more had a higher pooled OR [1.27; 95%CI (1.19;1.36)] than those with less participants. Although funnel plots showed some asymmetry, Egger tests were not statistically significant. Therefore, it is unlikely that the observed association was to publication bias. Early menarche is associated with hypertension among adult woman.


Health begins at home: the housing-health interface for older people.
Housing issues are of fundamental importance to the health and independence of older people in Britain, but this concept is not reflected in planning for health, housing, or community care. An analysis of community care plans and public health reports reflects how little attention the majority give either to the importance of housing or to the potential of primary care as a means of information exchange between older people and planning processes. Interviews with practitioners and policy makers in four cities, combined with a review of the considerable literature on planning and joint planning in the health and social services, helped to identify the problems in achieving more integrated systems. Structural blockages as fundamental as the definitions of 'health' and 'housing', the attitude of society to manual work, the hidden nature of the problems of older people, and the failure of planning to categorize according to the level of need are identified and summarized in a chart showing how these factors are linked and self-reinforcing. The article concludes with a vision of how things might work more effectively without requiring unrealistic changes. The authors offer a challenge to planners and joint commissioners to gather different kinds of information on need; to have long-term, as well as short-term, strategies; to think broadly across categories of issue; and to be prepared to invest money in new ways. Most significantly, by redefining the role of the Director of Public Health, we identify a focal point at which the responsibility and authority for coordinating, championing, and review could lie.


Seven novel macrocyclic polypeptides from Viola arvensis.
Seven novel macrocyclic polypeptides, designated as varv peptides B-H, have been isolated from the aerial parts of Viola arvensis. Their primary structures have been elucidated by automated Edman degradation and mass spectrometry. They all consist of 29 or 30 amino acid residues, covalently cyclized via the amide backbone and by three internal disulfide bridges. Their amino acid sequences are as follows: varv peptide B, cyclo-(TCFGGTCNTPGCSCDPWPMCSRNGLPVCGE); varv peptide C, cyclo-(TCVGGTCNTPGCSCSWPVCTRNGVPICGE); varv peptide D, cyclo-(TCVGGSCNTPGCSCSWPVCTRNGLPICGE); varv peptide E, cyclo-(TCVGGTCNTPGCSCSWPVCTRNGLPICGE); varv peptide F, cyclo-(TCTLGTCYTAGCSCSWPVCTRNGVPICGE); varv peptide G, cyclo-(TCFGGTCNTPGCSCDPWPVCSRNGVPVCGE); and varv peptide H, cyclo-(TCFGGTCNTPGCSCETWPVCSRNGLPVCGE). The varv peptides B-H exhibited high degrees of homology with the hitherto known macrocyclic peptides varv peptide A, kalata B1, violapeptide I, circulins A and B, and cyclopsychotride A.


Expression and localization of Drosophila melanogaster hsp70 cognate proteins.
Monoclonal antibodies have been used to identify three proteins in Drosophila melanogaster that share antigenic determinants with the major heat shock proteins hsp70 and hsp68. While two of the proteins are major proteins at all developmental stages, one heat shock cognate protein, hsc70, is especially enriched in embryos. hsc70 is shown to be the product of a previously identified gene, Hsc4. We have examined the levels of hsp70-related proteins in adult flies and larvae during heat shock and recovery. At maximal induction in vivo, hsp70 and hsp68 never reach the basal levels of the major heat shock cognate proteins. Monoclonal antibodies to hsc70 have been used to localize it to a meshwork of cytoplasmic fibers that are heavily concentrated around the nucleus.


Usefulness of the pediatric electrocardiogram in detecting left ventricular hypertrophy: results from the Prospective Pediatric Pulmonary and Cardiovascular Complications of Vertically Transmitted HIV Infection (P2C2 HIV) multicenter study.
A shortcoming of the pediatric electrocardiogram (ECG) appears to be its inability to accurately detect left ventricular hypertrophy (LVH). This study prospectively assesses the usefulness of the pediatric ECG as a screening modality for LVH. Concomitant echocardiograms and ECGs from a large cohort of children who were exposed to the human immunodeficiency virus (HIV; uninfected) and children who were infected with HIV were compared. By use of the values of Davignon et al, qualitative determination of LVH and quantitative criteria for LVH (RV6, SV1, RV6+SV1, QV6, and Q(III) >98% for age, R/SV1 <98% for age, and [-]TV6) were compared to body surface area adjusted for left ventricular (LV) mass z score. Results were then stratified according to weight and weight-for-height z scores. New age-adjusted predicted values were then constructed from children of a mixed race who were HIV-uninfected, < or =6 years old, and similarly assessed. The sensitivity rate was <20% for detecting increased LV mass, irrespective of HIV status; the specificity rate was 88% to 92%. The sensitivity rate of the individual criteria ranged from 0 to 35%; the specificity rate was 76% to 99%. Test sensitivities remained low when stratified by weight and weight-for-height z scores. Areas under the receiver operator characteristic curves were between 0.59 and 0.70, also suggesting poor accuracy of the ECG criteria. By use of new age-adjusted predicted values, the sensitivity rate decreased to <17%, and the specificity rate increased to 94% to 100%. The ECG is a poor screening tool for identifying LVH in children. Sensitivity is not improved with revision of current criteria.


The efficacy of multilevel surgery of the upper airway in adults with obstructive sleep apnea/hypopnea syndrome.
Many patients with obstructive sleep apnea/hypopnea syndrome (OSAHS) are incapable of using continuous positive airway pressure. These patients therefore turn to surgical options as a salvage treatment. Early studies and reviews focused on the efficacy of uvulopalatopharyngoplasty, a single-level procedure for the treatment of OSAHS. Since OSAHS is usually caused by multilevel obstructions, the true focus on efficacy should be on multilevel surgical intervention. The purpose of this paper is to provide an overview of the literature on multilevel surgery for OSAHS patients. Systematic review of the literature and meta-analysis focusing on subjective and objective outcomes of patients with OSAHS treated with multilevel surgery of the upper airway. We searched PubMed, the Cochrane database, and MEDLINE bibliographic databases up to March 31, 2007, for studies dealing with multilevel surgical modification of the upper airway for the treatment of OSAHS. Additional studies were identified from their reference lists. Articles were included only if the surgical intervention involved at least two of the frequently involved anatomic sites: nose, oropharynx, and hypopharynx. After applying specific inclusion criteria, 49 multilevel surgery articles (58 groups) were identified. There were 1,978 patients included in the study. The mean minimal follow-up time was 7.3 months (range, 1 to 100 months). A meta-analysis was performed to redefine the success rate to be consistent with the commonly agreed upon criteria, namely "a reduction in the apnea/ hypopnea index (AHI) of 50% or more and an AHI of less than 20." "Success" implies an improved condition and is not meant to imply cure. The recalculated success rate was 66.4%. The overall complication rate was 14.6%. The evidence-base medicine (EBM) level of these 49 studies revealed that only one study was EBM level 1, two papers were EBM level 3, and the other 46 papers were ranked as level 4 evidence. Multilevel surgery for OSAHS is obviously associated with improved outcomes, although this benefit is supported largely by level 4 evidence. Future research should focus on prospective and controlled studies.


Point Pair Feature-Based Pose Estimation with Multiple Edge Appearance Models (PPF-MEAM) for Robotic Bin Picking.
Automation of the bin picking task with robots entails the key step of pose estimation, which identifies and locates objects so that the robot can pick and manipulate the object in an accurate and reliable way. This paper proposes a novel point pair feature-based descriptor named Boundary-to-Boundary-using-Tangent-Line (B2B-TL) to estimate the pose of industrial parts including some parts whose point clouds lack key details, for example, the point cloud of the ridges of a part. The proposed descriptor utilizes the 3D point cloud data and 2D image data of the scene simultaneously, and the 2D image data could compensate the missing key details of the point cloud. Based on the descriptor B2B-TL, Multiple Edge Appearance Models (MEAM), a method using multiple models to describe the target object, is proposed to increase the recognition rate and reduce the computation time. A novel pipeline of an online computation process is presented to take advantage of B2B-TL and MEAM. Our algorithm is evaluated against synthetic and real scenes and implemented in a bin picking system. The experimental results show that our method is sufficiently accurate for a robot to grasp industrial parts and is fast enough to be used in a real factory environment.


Defining abstinence: views of directors, instructors, and participants in abstinence-only-until-marriage programs in Texas.
This study examined how program directors, instructors, and participant youth from a sample of federally funded abstinence-only-until-marriage education programs in Texas define the term "abstinence" and its object (from what one abstains). A sample of eight programs, from the 32 federally funded programs in the state (funded in fiscal year 2000-2001), were selected for indepth case studies. Interviews were conducted with 29 program staff (10 directors and 19 instructors). Six focus group sessions were held with youth participating in the programs. Interview and focus group transcripts were analyzed qualitatively, with salient themes being coded and counted. Results are presented in terms of frequency of mention of each theme/code. Most respondents (80% of program directors, 89% of instructors, 83% of focus groups) provided definitions of abstinence containing both positive and negative elements. Positive-patterned definitions emphasized specific attitudes and behaviors that must be internalized by youth (Internal Management; Values/Attitudes Incorporation; Abstinence as an Option; Investment in the Future). Negative definitions stressed restraint and avoidance, and focused on the objects of abstinence (Sexual/Vaginal Intercourse; Oral Sex; Anal Sex; Pre-Coital Behaviors; Behaviors with Purpose of Sexual Arousal; Non-Sexual Behaviors). Each element was mentioned by at least 26% of program staff and in at least 17% of youth focus groups. Results indicated substantial variability in how the term "abstinence" is defined. Such variability has implications for development of abstinence education programs, as well as for implementation of valid, equitable, and useful evaluations.


Yoga for secondary prevention of coronary heart disease.
Coronary heart disease (CHD) is the major cause of early morbidity and mortality in most developed countries. Secondary prevention aims to prevent repeat cardiac events and death in people with established CHD. Lifestyle modifications play an important role in secondary prevention. Yoga has been regarded as a kind of physical activity as well as stress management strategy. Growing evidence suggests the beneficial effects of yoga on various ailments. To determine the effectiveness of yoga for secondary prevention of mortality, morbidity, and health related quality of life of patients with CHD. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane Library (2012, Issue 1), MEDLINE (1948 to January 2012), EMBASE (1980 to January 2012), ISI Web of Science for conference proceedings (1970 to January 2012), China Journal Net (CJN) (1994 to March 2012), WanFang Data (1990 to March 2012), and HKInChiP (from 1980). Ongoing studies were identified in the metaRegister of Controlled Trials (April 2012) and the World Health Organization (WHO) International Clinical Trials Registry Platform (April 2012). No language restrictions were applied. We included randomized controlled trials (RCTs) investigating the influence of yoga practice on CHD outcomes. We included studies that had at least a six months follow-up period. Men and women (aged 18 years and above) with a diagnosis of acute or chronic CHD were included. We included studies with one group practicing a type of yoga compared to the control group receiving either no intervention or interventions other than yoga. Two authors independently selected studies according to the pre-specified inclusion criteria. Disagreements were resolved by consensus or discussion with a third author. We found no eligible RCTs that met the inclusion criteria of the review and thus we were unable to perform a meta-analysis. The effectiveness of yoga for secondary prevention in CHD remains uncertain. Large RCTs of high quality are needed.


Cytomegalovirus-induced inactivation of TSC2 disrupts the coupling of fatty acid biosynthesis to glucose availability resulting in a vulnerability to glucose limitation.
Human cytomegalovirus (HCMV) modulates cellular metabolism to support productive infection, and the HCMV UL38 protein drives many aspects of this HCMV-induced metabolic program. However, it remains to be determined whether virally-induced metabolic alterations might induce novel therapeutic vulnerabilities in virally infected cells. Here, we explore how HCMV infection and the UL38 protein modulate cellular metabolism and how these changes alter the response to nutrient limitation. We find that expression of UL38, either in the context of HCMV infection or in isolation, sensitizes cells to glucose limitation resulting in cell death. This sensitivity is mediated through UL38's inactivation of the TSC complex subunit 2 (TSC2) protein, a central metabolic regulator that possesses tumor-suppressive properties. Further, expression of UL38 or the inactivation of TSC2 results in anabolic rigidity in that the resulting increased levels of fatty acid biosynthesis are insensitive to glucose limitation. This failure to regulate fatty acid biosynthesis in response to glucose availability sensitizes cells to glucose limitation, resulting in cell death unless fatty acid biosynthesis is inhibited. These experiments identify a regulatory circuit between glycolysis and fatty acid biosynthesis that is critical for cell survival upon glucose limitation and highlight a metabolic vulnerability associated with viral infection and the inactivation of normal metabolic regulatory controls.


Creating patient value in glaucoma care: applying quality costing and care delivery value chain approaches--a five-year case study in the Rotterdam Eye Hospital.
The purpose of this paper is to explore in a specific hospital care process the applicability in practice of the theories of quality costing and value chains. In a retrospective case study an in-depth evaluation of the use of a quality cost model (QCM) and the applicability of Porter's care delivery value chain (CDVC) was performed in a specific care process: glaucoma care over the period 2001 to 2006 in the Rotterdam Eye Hospital in The Netherlands. The case study shows a reduction of costs per product by increasing the number of outpatient visits and surgery combined with a higher patient satisfaction. Reduction of costs of non-compliance by using the QCM is small, due to the absence of (external) financial incentives for both the hospital and individual physicians. For CDVC to be supportive to an integrated quality and cost management the notion "patient value" needs far more specification as mutually agreed on by the stakeholders involved and related reimbursement needs to depend on realised outcomes. The case study just focused on one specific care process in one hospital. To determine effects in other areas of health care, it is important to study the use and applicability of the QCM and the CDVC in other care processes and settings. QCM and a CDVC can be useful tools for hospital management to manage the outcomes on both quality and costs, but impact is dependent on the incentives in the context of the existing organisational and reimbursement system and asks for an agreed on operationalisation among the various stakeholders of the notion of patient value.


Evaluation of the Final Adult Height and Its Determinants in Patients with Growth Hormone Deficiency: A Single-centre Experience from the South-Eastern Region of Turkey
The aim was to determine the final adult height (FAH) achieved by recombinant human growth hormone (rhGH) treatment, the factors affecting FAH and the success of attaining the genetic potential. Data of 133 patients treated with rhGH therapy were reviewed retrospectively. Patients were grouped according to diagnosis, either isolated GH deficiency (IGHD) or multiple pituitary hormone deficiency (MPHD), and by sex, and pubertal status at the beginning of treatment. The mean age of initiation of treatment was 12.3±2.18 years, and the mean duration of rhGH treatment was 3.65±1.5 years. The mean height standard deviation score (SDS) at diagnosis was -3.11±0.75 SD. All patients received a standardized GH dose of 0.033 mg/kg/day. Mean FAH-SDS was -1.8±0.77 and delta height-SDS (the change in height SDS between the beginning and end of treatment) was 1.28±0.94 SD. FAH-SDS was -1.79±0.86 SD in males; -1.82±0.64 in females (p=0.857); -1.94±0.71 at the beginning of treatment in pubertal patients and -1.68±0.81 in prepubertal patients (p=0.056); -1.84±0.89 in patients with IGHD and -0.47±0.2 in patients with MPHD (p˃0.05). In multiple regression analysis, First year delta height-SDS was the most predictive factor for both FAH-SDS and delta height-SDS. The majority of our patients achieved a final height compatible with their genetic potential as well as population standards when treated with rhGH even having started at a relatively late age. First year delta height-SDS was a predictive factor for FAH.


A perspective on "cure" for Rett syndrome.
The reversal of the Rett syndrome disease process in the Mecp2 mouse model of Guy et al. (2007) has motivated families and researchers to work on this condition. The reversibility in adult mice suggests that there is potentially much to be gained from rational treatments applied to patients of any age. However, it may be difficult to strike the right balance between enthusiasm on the one hand and realism on the other. One effect of this has been a fragmentation of the "Rett syndrome community" with some groups giving priority to work aimed at a cure while fewer resources are devoted to medical or therapy-based interventions to enhance the quality of life of affected patients or provide support for their families.Several possible therapeutic approaches are under development that, it is claimed and hoped, may lead to a "cure" for patients with Rett syndrome. While all have a rationale, there are potential obstacles to each being both safe and effective. Furthermore, any strategy that succeeded in restoring normal levels of MECP2 gene expression throughout the brain carries potential pitfalls, so that it will be of crucial importance to introduce any clinical trials of such therapies with great care.Expectations of families for a radical, rational treatment should not be inflated beyond a cautious optimism. This is particularly because affected patients with us now may not be able to reap the full benefits of a "cure". Thus, interventions aimed at enhancing the quality of life of affected patients should not be forgone and their importance should not be minimised.


Long-term phosphorus fertility in wastewater-irrigated cropland.
Land treatment of municipal wastewater effluent is a proven method for augmenting freshwater resources and avoiding direct nutrient discharges to surface waters. We assessed changes in soil test phosphorus (P) of the Ap horizon of cropped fields continuously irrigated for 26 yr with secondary effluent from the Penn State University wastewater treatment plant. For annual P additions averaging 97 kg P ha(-1), Mehlich-3 P (M3P) response in the 0- to 20-cm surface soil (initially < 20 mg kg(-1)) was represented by two lines. For the first 12 yr of irrigation, soil test P increased, with 14.5 kg P ha(-1) needed to increase M3P by 1 mg P kg(-1). After the initial buildup, M3P maintained a quasi-steady-state value of approximately 110 mg kg(-1). Over time, the surface soil equilibrium P concentration at zero sorption increased markedly (from < 1 to 5.5 mg P L(-1)), and extractable aluminum (Al) decreased significantly (P < 0.001). Speciation modeling using Visual MINTEQ suggests complexation of Al by dissolved organic carbon at site pH conditions. Loss of Al from the surface layer lowered its P-sorbing capacity, causing added effluent-P to move into the subsoil. Results suggest that current management practices can continue for many years without exceeding the surface soil M3P environmental threshold (200 mg kg(-1)) used in state P-based nutrient policies.


A vital signs telemonitoring system - interoperability supported by a personal health record systema and a cloud service.
This article presents the development process of an acquisition and data storage system managing clinical variables through a cloud storage service and a Personal Health Record (PHR) System. First, the paper explains how a Wireless Body Area Network (WBAN) that captures data from two sensors corresponding to arterial pressure and heart rate is designed. Second, this paper illustrates how data collected by the WBAN are transmitted to a cloud storage service. It is worth mentioning that this cloud service allows the data to be stored in a persistent way on an online database system. Finally, the paper describes, how the data stored in the cloud service are sent to the Indivo PHR System, where they are registered and charted for future revision by health professionals. The research demonstrated the feasibility of implementing WBAN networks for the acquisition of clinical data, and particularly for the use of Web technologies and standards to provide interoperability with PHR Systems at technical and syntactic levels.


Glaucoma Detection Ability of Macular Ganglion Cell-Inner Plexiform Layer Thickness in Myopic Preperimetric Glaucoma.
We evaluated the glaucoma detection ability of macular ganglion cell-inner plexiform layer (GCIPL) thickness measured by spectral-domain optical coherence tomography (SD-OCT) and compared it to peripapillary retinal nerve fiber layer (RNFL) thickness and optic nerve head (ONH) parameters in myopic preperimetric glaucoma (PPG). We analyzed 353 eyes, including 67 nonmyopic preperimetric glaucomatous eyes, 182 myopic healthy eyes, and 104 myopic preperimetric glaucomatous eyes. Myopic PPG detection abilities of the respective parameters were assessed by calculating the area under receiver operating characteristic (AUROC) curves. The myopic eyes were divided into two groups (a nonhighly myopic and a highly myopic group). The diagnostic performance was analyzed for each group independently, and differences between the two groups also were evaluated. The best parameter for discrimination of myopic PPG from myopic healthy eyes was inferotemporal macular GCIPL thickness. The AUROCs of this parameter were 0.752, 0.747, and 0.737 in the total myopic, nonhighly myopic, and highly myopic groups, respectively. These were significantly larger than the AUROCs of the other parameters, including average RNFL thickness, average GCIPL thickness, rim area, inferior RNFL thickness, and minimum GCIPL thickness (P = 0.021, 0.012, 0.016, 0.036, and 0.013, respectively). The inferotemporal macular GCIPL thickness showed no significant difference between nonhighly myopic and highly myopic groups. The inferotemporal macular GCIPL thickness was the best PPG-detection parameter for myopic eyes. Inferotemporal macular GCIPL thickness evaluation can be considered to be a useful means of diagnosing PPG in myopic eyes.


Phosphatidylcholine metabolism during renal growth and regeneration.
Phosphatidylcholine, the most abundant phospholipid in renal cellular membranes, is synthesized predominantly via the Kennedy pathway in normal and growing kidney tissue. Augmented biosynthesis of phosphatidylcholine is one of the earliest responses to growth signals in renal cells. During potassium depletion, regeneration after acute tubular necrosis, and compensatory growth after uninephrectomy increased membrane phosphatidylcholine biosynthesis precedes the appearance of new organelles and surface structures and the onset of cell division. The increment in phosphatidylcholine biosynthesis in the growing kidneys of potassium-depleted rats appears to be mediated by enhanced cellular uptake of the precursor choline and activation of the enzyme cytidine diphosphocholine:1,2-diacylglycerol cholinephosphotransferase. Specific amino acids, cations, and polyamines can modify the activity of this microsomal enzyme in normal and growing renal cells. Phospholipase A also plays a regulatory role in phosphatidylcholine metabolism because inhibition of this catabolic enzyme favors phospholipid accretion and kidney growth during potassium depletion, whereas stimulation of the enzyme leads to brisk phospholipid breakdown and a decrease in tissue mass during potassium repletion.


Characterization of ovine utero-placental interface tensile failure.
Data on the strength of the utero-placental interface (UPI) would help improve understanding of the mechanisms of placental abruption (premature separation of the placenta from the uterus) during motor-vehicle crashes involving pregnant occupants. An ovine model was selected for study because like the human, its placenta has a villous attachment structure. Uteri with intact placentas were obtained from three sheep as by-products of another research study. The samples were harvested between 102 and 119 days of the 145-day gestational period. Rectangular specimens with areas measuring 15 mm × 5 mm were cut through the thickness of the placenta and uterus. Each subject provided eight samples, of which four were tested at a nominal strain rate of 0.10 strains/sec and the remainder was tested at a nominal strain rate of 1.0 strains/sec. Sutures were used to secure the uterine side of the specimens to the test fixture, while mechanical clamps were used to attach the placenta side. A FARO arm scanner recorded the initial geometry of the tissue, and a random dot pattern applied to the placenta and uterus tissue allowed visualization of displacement. For the structure of the UPI, mean tensile failure strain and standard deviations are 0.37 (0.11) and 0.37 (0.18) for the 0.10 and 1.0 strain rates, respectively (p-value = 0.970) while the associated failure stresses are 6.5 (1.37) and 15.0 (5.08) kPa, (p-value = 0.064). The results from sheep UPI testing provide the first estimate of the human UPI structural failure tolerance.


Mediating effects of depression on sleep disturbance and frailty in older adult type 2 diabetes patients in the community.
With the progressive aging of the population, frailty is now a significant challenge in geriatrics research. A growing amount of evidence suggests that sleep disturbance and depression have independent effects on frailty, although the underlying mechanisms are not yet clear. This study aimed to investigate the mediating role of depression in the relationship between sleep disturbance and frailty in older adult patients with type 2 diabetes (T2DM) in the community. Purposive sampling was used to collect face-to-face data from 342 community-dwelling T2DM patients in Chengdu, Sichuan Province, China, between February and May 2023. The Pittsburgh Sleep Quality Index (PSQI) scale was used to evaluate sleep quality, the Simple Geriatric Depression Scale (GDS-15) was used to evaluate depressive symptoms, and the FRAIL Scale (FRAIL) was used to evaluate frailty. Linear regression equation and bootstrap self-sampling were used to verify the mediating role of depressive symptoms in sleep disturbance and frailty. The study found that sleep disturbance had a direct positive effect with frailty [β = 0.040, 95% CI: (0.013, 0.069)]. Additionally, depression had a direct positive effect on frailty [β = 0.130, 95% CI: (0.087, 0.173)], and depression was found to partially mediate the relationship between sleep disturbance and frailty. Poor sleep quality and frailty are common in patients with T2DM. To reduce the frailty of older adult T2DM patients, all levels of society (government, medical institutions, and communities) must pay more attention to mental health. A variety of interventions should be considered to improve sleep quality and depression, which in turn may prevent or control frailty.


Pain-Relieving Effect of 4.4 MHz of Pulsed Radiofrequency on Acute Knee Arthritis in Rats.
Drug injections and surgery are popular treatments for knee joint osteoarthritis. However, these treatments are invasive, and new noninvasive treatments with similar or better efficacy are needed. Here, we evaluated the application of 4.4 MHz of pulsed radiofrequency (PRF) as a new treatment. Acute arthritis was induced by injection of carrageenan into the intra-articular space of the knee in male rats. At 4.5 hours after arthritis induction, PRF with the treatment protocol of three seconds on and off was applied to the affected knee joint for 20 minutes. The changes in pain behavior were evaluated by comparing the peak weight load values of both hind paws at pretreatment and four, six, seven, eight, and 24 hours after treatment. And we also used Western blotting and immunohistochemistry to measure the inflammatory changes in the synovial membrane of the inflamed knee. We found that the 20-minute application of PRF with the treatment protocol significantly recovered the weight load reduction at six-, seven-, and eight-hour time points after carrageenan injection. COX-2 and IL-1β levels were significantly reduced in the inflamed rats after PRF application at six and eight hours post-carrageenan injection. Immunohistochemistry showed that PRF significantly reduced inflammatory cell infiltration at six hours post-carrageenan injection. . Our results indicate that noninvasive PRF application inhibited pain-related behavior and decreased inflammatory cytokine expression in the inflamed knee joints of rats. Accordingly, PRF application can serve as a potential therapeutic treatment to relieve pain associated with peripheral joint/tissue damage or inflammation.


Reverse and conventional chemical ecology approaches for the development of oviposition attractants for Culex mosquitoes.
Synthetic mosquito oviposition attractants are sorely needed for surveillance and control programs for Culex species, which are major vectors of pathogens causing various human diseases, including filariasis, encephalitis, and West Nile encephalomyelitis. We employed novel and conventional chemical ecology approaches to identify potential attractants, which were demonstrated in field tests to be effective for monitoring populations of Cx. p. quinquefasciatus in human dwellings. Immunohistochemistry studies showed that an odorant-binding protein from this species, CquiOBP1, is expressed in trichoid sensilla on the antennae, including short, sharp-tipped trichoid sensilla type, which house an olfactory receptor neuron sensitive to a previously identified mosquito oviposition pheromone (MOP), 6-acetoxy-5-hexadecanolide. CquiOBP1 exists in monomeric and dimeric forms. Monomeric CquiOBP1 bound MOP in a pH-dependent manner, with a change in secondary structure apparently related to the loss of binding at low pH. The pheromone antipode showed higher affinity than the natural stereoisomer. By using both CquiOBP1 as a molecular target in binding assays and gas chromatography-electroantennographic detection (GC-EAD), we identified nonanal, trimethylamine (TMA), and skatole as test compounds. Extensive field evaluations in Recife, Brazil, a region with high populations of Cx. p. quinquefasciatus, showed that a combination of TMA (0.9 microg/l) and nonanal (0.15 ng/microl) is equivalent in attraction to the currently used infusion-based lure, and superior in that the offensive smell of infusions was eliminated in the newly developed synthetic mixture.


[Life and medical missionary activities of Esther K. Pak (1877-1910)].
Esther K. Pak (1876-1910) is believed as the first medical doctor in Korea. Esther's life can be largely reviewed in three parts: school-hood at EwhaHaktang (currently Ewha Womans University), Education in the United States, and medical missionary work after coming back to Korea from the United States. The foreign Methodist missionaries was able to enter Korea after opening of its ports and establishing its diplomatic relationship with the United States. Esther met modern sciences and Christianity at EwhaHaktang, which was founded by those missionaries. She could dream of being an American-style medical doctor in the future, while she assisted medical missionaries at PoKuNyoKwan in EwhaHaktang. She could get substantial academic help from those missionaries. With the support of Dr. Rosetta Sherwood Hall, who first introduced the world of medial science to Esther in a real sense, Esther went to the United States to study the field in 1894. While learning it, she suffered from academic frustration, economic difficulty, her husband's death and so on, but she eventually got over those adversities and completed the four years of academic courses to become a medical doctor. Her religious faith and will to help Koreans as a doctor encouraged her to finish what she had originally planned. Esther came back to Korea in 1900 and began to work earnestly as a medical missionary delegated from Woman's Foreign Missionary Society. At PoKuNyoKwan in Seoul and Woman's Hospital in Pyongyang, She performed medical work and enlightenment campaign against the superstitious healing conduct. Esther also took part in the circuit missionary performances. She devoted herself for evangelical work at Bible Institute as well. Esther's activity made people understand the effectiveness of education. She helped people to recognize education for woman, occidental medical treatment and Christianity in a positive way. On April 28, 1909, based on these excellent performances for the social development, she was invited, honored and granted a testimonial at the first welcoming ceremony, which was held by the united body of civilians and officials, for students studying abroad. But on April 13, 1910, about one year after the ceremony, she died of illness. She was 34. Although she was born at the turbulent last period of Korea Empire and lived for only 34 years, Esther's medical missionary work was evaluated as the opening of woman's participation in medical science in Korea. Not only in the 'woman's' but also in 'whole' field of medical science, her performance left significant marks in woman's and Christian history in Korea as well.


[Clinical, hemodynamic and neurohumoral effects of long-term therapy of patients with severe chronic heart failure with beta-adrenoblocker bisoprolol].
The use of beta-adrenoblockers in conjunction with angiotensin converting enzyme inhibitors improves quality of life and prognosis of patients with chronic heart failure. However basic mechanisms of these positive effects in severe heart failure remain to be elucidated. Patients (n=54) with NYHA class III-IV heart failure and left ventricular ejection fraction < or =35% were randomized either to treatment with bisoprolol (1.25-10 mg/day) (n=30) or in control group (n=24) and were followed up for 12 months. The use of bisoprolol was associated with significant improvement of heart failure functional class, lowering of heart rate (by 14%, p<0.01), elevation of systolic blood pressure (by 7.2+/-12.3 mm Hg, p<0.01) and increase of walking distance (by 30.1+/-29.0 m, p<0.01). No significant changes of these parameters occurred in control group. After 12 months increases of left ventricular end diastolic and end systolic volumes (by 85+/-69.2 and 71+/-51.5 ml, respectively, p<0.001) and of ejection fraction (by 5.7+/-7.3%, p<0.01) took place in bisoprolol treated patients. These changes were significantly (p<0.001) higher than those in control group. After 6 months of treatment with bisoprolol noradrenaline concentration fell from 533 to 402 pg/ml (p<0.05) while in controls it rose from 369 to 474 pg/ml, p<0.01). Decreases of plasma renin activity (from 1.2 to 0.42 ng/ml/h), plasma concentrations of angiotensin II (from 17.1 to 13.1 pg/ml) and aldosterone (from 173 to 148 pg/ml, p<0.05) were also observed in bisoprolol group. No substantial dynamics of activity of main components of renin angiotensin system took place in controls. There were no significant changes of atrial natriuretic peptide in both groups. Significant positive dynamics of parameters of heart rate variability was registered only in bisoprolol group: SDNN increased by 25% (p<0.05), high frequency spectrum by 106% (p=0.03), LF/HF ratio from 2.18+/-1.41 to 1.82+/-0.7. Long term use of bisoprolol was associated with improved clinical and hemodynamic status, increased systolic BP, blocked processes of pathological left ventricular remodeling, lowered activity of not only sympathetic-adrenal but also of main components of renin-angiotensin system and improved heart rate variability.


Vertical variations in wood CO2 efflux for live emergent trees in a Bornean tropical rainforest.
Difficult access to 40-m-tall emergent trees in tropical rainforests has resulted in a lack of data related to vertical variations in wood CO2 efflux, even though significant variations in wood CO2 efflux are an important source of errors when estimating whole-tree total wood CO2 efflux. This study aimed to clarify vertical variations in wood CO2 efflux for emergent trees and to document the impact of the variations on the whole-tree estimates of stem and branch CO2 efflux. First, we measured wood CO2 efflux and factors related to tree morphology and environment for seven live emergent trees of two dipterocarp species at four to seven heights of up to ∼ 40 m for each tree using ladders and a crane. No systematic tendencies in vertical variations were observed for all the trees. Wood CO2 efflux was not affected by stem and air temperature, stem diameter, stem height or stem growth. The ratios of wood CO2 efflux at the treetop to that at breast height were larger in emergent trees with relatively smaller diameters at breast height. Second, we compared whole-tree stem CO2 efflux estimates using vertical measurements with those based on solely breast height measurements. We found similar whole-tree stem CO2 efflux estimates regardless of the patterns of vertical variations in CO2 efflux because the surface area in the canopy, where wood CO2 efflux often differed from that at breast height, was very small compared with that at low stem heights, resulting in little effect of the vertical variations on the estimate. Additionally, whole-tree branch CO2 efflux estimates using measured wood CO2 efflux in the canopy were considerably different from those measured using only breast height measurements. Uncertainties in wood CO2 efflux in the canopy did not cause any bias in stem CO2 efflux scaling, but affected branch CO2 efflux.


Response of thawed epididymal red deer spermatozoa to increasing concentrations of hydrogen peroxide, and importance of individual male variability.
Oxidative stress represents a challenge during sperm manipulation. We have tested the effect of increasing hydrogen peroxide (H(2)O(2)) levels on red deer spermatozoa after cryopreservation, and the role of male-to-male variation in that response. In a first experiment, eight thawed samples were submitted to 0, 25, 50, 100 and 200 μm H(2)O(2) for 2 h at 37 °C. Intracellular reactive oxygen species (H(2)DCFDA-CM) increased with H(2)O(2) concentration, but we only detected a decrease in sperm function (motility by CASA and chromatin damage by sperm chromatin structure assay) with 200 μm. Lipoperoxidation assessed by the thiobarbituric acid reactive substance (TBARS) method increased slightly with 50 μm H(2)O(2) and above. In a second experiment, samples from seven males were submitted to 0 and 200 μm H(2)O(2) for 2 h, triplicating the experiment within each male. Males differed at thawing and regarding their response to incubation and H(2)O(2) presence. We found that the kinematic parameters reflected male-to-male variability, whereas the response of the different males was similar for lipid peroxidation and viability. A multiparametric analysis showed that males grouped differently if samples were assessed after thawing, after incubation without H(2)O(2) or after incubation with H(2)O(2) . Red deer spermatozoa are relatively resilient to H(2)O(2) after thawing, but it seems to be a great male-to-male variability regarding the response to oxidative stress. The acknowledgement of this individual variability might improve the development of optimized sperm work protocols.


Mannuronan C-5-epimerases and their application for in vitro and in vivo design of new alginates useful in biotechnology.
The industrially important polysaccharide alginate is a linear copolymer of beta-D-mannuronic acid (M) and alpha-L-guluronic acid (G). It is produced commercially by extraction from brown seaweeds, although some of the bacteria belonging to the genera Azotobacter and Pseudomonas also synthesize alginates. Alginates are synthesized as mannuronan, and varying amounts of the M residues in the polymer are then epimerized to G residues by mannuronan C-5-epimerases. The gel-forming, water-binding, and immunogenic properties of the polymer are dependent on the relative amount and sequence distribution of M and G residues. A family of seven calcium-dependent, secreted epimerases (AlgE1-7) from Azotobacter vinelandii have now been characterized, and in this paper the properties of all these enzymes are described. AlgE4 introduces alternating M and G residues into its substrate, while the remaining six enzymes introduce a mixture of continuous stretches of G residues and alternating sequences. Two of the enzymes, AlgE1 and AlgE3, are composed of two catalytically active domains, each introducing different G residue sequence patterns in alginate. These results indicate that the enzymes can be used for production of alginates with specialized properties.


Proteolysis in cultured cells during prolonged serum deprivation and replacement.
Cells in culture show a series of changes in intracellular protein degradation in response to serum deprivation and replacement that are similar to alterations in degradation in tissues of starved and refed animals. Rates of intracellular protein degradation are increased in confluent cultures of IMR-90 human diploid fibroblasts when deprived of serum, but this enhanced proteolysis is transient. By 24-48 h, rates of protein degradation decline to values comparable to or below those for cells incubated in the presence of serum. Longer serum deprivation leads to further reductions in proteolysis. The reduced proteolysis after long-term deprivation cannot be explained by experimental artifacts or by gradual depletion of glucocorticoids or thyroid hormones from cells. Readdition of serum to deprived cells that are still in the enhanced phase of proteolysis restores degradation rates to values comparable to those in nondeprived cells. However, in cells deprived of serum for 24-48 h or longer, readdition of serum to the medium results in a marked reduction in proteolysis to rates below those observed in nondeprived cells. These responses of cultured cells to long-term serum deprivation and readdition may be of considerable physiological importance in that the proteolytic responses of tissues in starved and refed animals may be at least partially due to mechanisms operating at the cellular level.


Glucose Uptake and Intracellular pH in a Mouse Model of Ductal Carcinoma In situ (DCIS) Suggests Metabolic Heterogeneity.
Mechanisms for the progression of ductal carcinoma in situ (DCIS) to invasive breast carcinoma remain unclear. Previously we showed that the transition to invasiveness in the mammary intraepithelial neoplastic outgrowth (MINO) model of DCIS does not correlate with its serial acquisition of genetic mutations. We hypothesized instead that progression to invasiveness depends on a change in the microenvironment and that precancer cells might create a more tumor-permissive microenvironment secondary to changes in glucose uptake and metabolism. Immunostaining for glucose transporter 1 (GLUT1) and the hypoxia marker carbonic anhydrase 9 (CAIX) in tumor, normal mammary gland and MINO (precancer) tissue showed differences in expression. The uptake of the fluorescent glucose analog dye, 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxy-D-glucose (2-NBDG), reflected differences in the cellular distributions of glucose uptake in normal mammary epithelial cells (nMEC), MINO, and Met1 cancer cells, with a broad distribution in the MINO population. The intracellular pH (pHi) measured using the fluorescent ratio dye 2',7'-bis(2-carboxyethyl)-5(6)-155 carboxyfluorescein (BCECF) revealed expected differences between normal and cancer cells (low and high, respectively), and a mixed distribution in the MINO cells, with a subset of cells in the MINO having an increased rate of acidification when proton efflux was inhibited. Invasive tumor cells had a more alkaline baseline pHi with high rates of proton production coupled with higher rates of proton export, compared with nMEC. MINO cells displayed considerable variation in baseline pHi that separated into two distinct populations: MINO high and MINO low. MINO high had a noticeably higher mean acidification rate compared with nMEC, but relatively high baseline pHi similar to tumor cells. MINO low cells also had an increased acidification rate compared with nMEC, but with a more acidic pHi similar to nMEC. These findings demonstrate that MINO is heterogeneous with respect to intracellular pH regulation which may be associated with an acidified regional microenvironment. A change in the pH of the microenvironment might contribute to a tumor-permissive or tumor-promoting progression. We are not aware of any previous work showing that a sub-population of cells in in situ precancer exhibits a higher than normal proton production and export rate.


Wavelet transform in electrocardiography--data compression.
An application of the wavelet transform to electrocardiography is described in the paper. The transform is used as a first stage of a lossy compression algorithm for efficient coding of rest ECG signals. The proposed technique is based on the decomposition of the ECG signal into a set of basic functions covering the time-frequency domain. Thus, non-stationary character of ECG data is considered. Some of the time-frequency signal components are removed because of their low influence to signal characteristics. Resulting components are efficiently coded by quantization, composition into a sequence of coefficients and compression by a run-length coder and a entropic Huffman coder. The proposed wavelet-based compression algorithm can compress data to average code length about 1 bit/sample. The algorithm can be also implemented to a real-time processing system when wavelet transform is computed by fast linear filters described in the paper.


Septic arthritis due to Aerococcus viridans.
A 20-year-old woman was found to have septic arthritis of the hip due to Aerococcus viridans. This organism closely resembles Streptococcus viridans, but forms gram positive tetrads rather than chains in broth media. The organism has been reported rarely to cause endocarditis and one case of osteomyelitis has been observed. To our knowledge septic arthritis due to Aerococcus viridans has not been previously reported.


Dose confirmation of a novel fixed dose combination injectable (0.2 mg/kg doramectin + 6.0 mg/kg levamisole hydrochloride) against naturally acquired gastrointestinal nematodes in US cattle.
Macrocyclic lactone (ML) resistance in cattle gastrointestinal nematodes (GINs) is an increasing problem. Concurrent combination anthelmintic therapy incorporating an existing ML with a second drug class has been proposed to control cattle GINs while slowing the development of ML resistance. Two dose confirmation studies were conducted to investigate the efficacy of a new fixed-dose combination injectable (FDCI) anthelmintic against common cattle GINs known to negatively impact production. The FDCI is formulated with 5 mg/ml doramectin and 150 mg/ml levamisole hydrochloride (HCl). Cattle enrolled in the two studies were sourced from either the Southern (Study 1, n = 30) or Midwest (Study 2, n = 36) United States. Animals with GIN infections confirmed by fecal egg count (FEC) were randomly allocated to one of three treatment groups. On Day 0, cattle with positive FECs on Day -5( ± 2) were weighed and administered a single subcutaneous injection of either saline (0.9% sodium chloride) at 0.04 ml/kg, 10 mg/ml doramectin at 0.02 ml/kg (to provide 0.2 mg/kg doramectin) or the FDCI at 0.04 ml/kg (to provide 0.2 mg/kg doramectin and 6.0 mg/kg levamisole HCl). On Day 14, fecal samples were collected, animals were euthanized, and worms were collected from the intestinal tract of each animal. Treatment efficacy was calculated using worm burdens and the fecal egg count reduction test (FECRT). Pre-treatment (Day -5, Study 1; Day -3, Study 2) mean FECs were 999.4-1136.2 eggs per gram (EPG) in Study 1 and 137.1-226.6 EPG in Study 2. The FDCI was active against cattle GIN populations in both studies, with FECRT ≥ 99.98% in both studies. Compared to saline-treated cattle, FDCI-treated cattle had significantly fewer adult and immature worms of all identified species on Day 14. In Study 1, Day 14 efficacy of the FDCI was 96.9% for Cooperia spp. (C. oncophora (99.7%) and C. punctata (95.9%)), 99.1% for Nematodirus helvetianus, and 99.8% for Ostertagia spp. In Study 2, the FDCI provided 100% efficacy against all adult GIN species identified, including all GINs identified in Study 1 and Trichostrongylus axei. The FDCI also provided 95.5% efficacy against immature Ostertagia spp. and 100% efficacy against immature Cooperia spp. (Study 2). Doramectin was effective against all adult cattle GINs (except N. helvetianus) in Study 2 but was only effective against adult Ostertagia spp. in Study 1. Additionally, doramectin was only effective against immature Cooperia spp. (and not immature Ostertagia spp.) in Study 2. A single administration of the doramectin + levamisole HCl FDCI provides a new and effective approach to the treatment and control of common cattle GINs, including those exhibiting decreased susceptibility to doramectin alone.


Differences in methylation patterns of the alpha-fetoprotein and albumin genes in hepatic and non hepatic developing rat tissues.
By use of different restriction enzymes sensitive to internal cytosine methylation (HpaII, AvaI, HhaI) we have analysed the methylation patterns of albumin and AFP genes in tissues and cell lines with high (liver, yolk sac, hepatoma cell lines), low (fetal and neonatal kidney) or undetectable (spleen, JF1 fibroblasts) expression of either gene. We show that expression of the AFP gene is associated to the demethylation of a whole region or domain extending from -4 to +3 Kb. Moreover, demethylation of a site located at the upstream limit of this domain appears to be correlated with the commitment of the cell type to synthesize AFP. As concerns the albumin gene, we show that the domain in which demethylation is correlated with active gene transcription in hepatoma cell lines has different borders than in tissue. This difference might be related to the different amounts of mRNA synthesized or to an alteration in gene regulation in tumor cells. Finally, we show that low expression of albumin and AFP genes in fetal and neonatal kidney is not correlated with domain demethylation, suggesting that the regulatory mechanisms of expression of these genes are different in kidney as compared with liver.


Phenotypic variability and genetic susceptibility to genomic disorders.
The duplication architecture of the human genome predisposes our species to recurrent copy number variation and disease. Emerging data suggest that this mechanism of mutation contributes to both common and rare diseases. Two features regarding this form of mutation have emerged. First, common structural polymorphisms create susceptible and protective chromosomal architectures. These structural polymorphisms occur at varying frequencies in populations, leading to different susceptibility and ethnic predilection. Second, a subset of rearrangements shows extreme variability in expressivity. We propose that two types of genomic disorders may be distinguished: syndromic forms where the phenotypic features are largely invariant and those where the same molecular lesion associates with a diverse set of diagnoses including epilepsy, schizophrenia, autism, intellectual disability and congenital malformations. Copy number variation analyses of patient genomes reveal that disease type and severity may be explained by the occurrence of additional rare events and their inheritance within families. We propose that the overall burden of copy number variants creates differing sensitized backgrounds during development leading to different thresholds and disease outcomes. We suggest that the accumulation of multiple high-penetrant alleles of low frequency may serve as a more general model for complex genetic diseases, posing a significant challenge for diagnostics and disease management.


Redox Control over Acyl Hydrazone Photoswitches.
Photoisomerization provides a clean and efficient way of reversibly altering physical properties of chemical systems and injecting energy into them. These effects have been applied in development of systems such as photoresponsive materials, molecular motors, and photoactivated drugs. Typically, switching from more to less stable isomer(s) is performed by irradiation with UV or visible light, while the reverse process proceeds thermally or by irradiation using another wavelength. In this work we developed a method of rapid and tunable Z→E isomerization of C═N bond in acyl hydrazones, using aromatic thiols as nucleophilic catalysts. As thiols can be oxidized into catalytically inactive disulfides, the isomerization rates can be controlled via the oxidation state of the catalyst, which, together with the UV irradiation, provides orthogonal means to control the E/Z state of the system. As a proof of this concept, we have applied this method to control the diversity of acyl hydrazone based dynamic combinatorial libraries.


Feeding intolerance following ophthalmologic examination.
Reports of isolated cases of necrotizing enterocolitis following administration of mydriatric medication and ophthalmologic examination prompted a comparison of the incidence of feeding difficulties 24 hours before and 24 hours after the ophthalmologic examination of 50 newborns. All infants had received cyclopentolate hydrochloride and phenylephrine hydrochloride before the examination. A critical review of the nursing notes showed more abdominal distention and gastric aspirates in the period following the examination than in the period preceding the examination. One infant developed necrotizing enterocolitis during the 24-hour postexamination period. This study demonstrates the risk of feeding intolerance following the ophthalmologic examination of neonates. These risks may be due to the known side effects of the mydriatics, to the physical stress of the examination, or to a combination of both factors.


Oral rehabilitation with implant-supported fixed partial dentures in periodontitis-susceptible subjects. A 5-year prospective study.
Comparatively few studies with at least 5 years of follow-up are available that describe the use of implants in prosthetic rehabilitation of partially edentulous patients. Randomized, controlled clinical studies that evaluated the effect of different surface designs of screw-shaped implants on the outcome of treatment are also sparse. To determine, in a prospective randomized, controlled clinical trial, the outcome of restorative therapy in periodontitis-susceptible patients who, following basic periodontal therapy, had been restored with implants with either a machined- or a rough-surface topography. Fifty-one subjects (mean age, 59.5 years), 20 males and 31 females who, following treatment of moderate-to-advanced chronic periodontitis, required implant therapy for prosthetic rehabilitation were recruited. Seventeen of the patients were current smokers. Following the active treatment, all subjects were included in an individually designed maintenance program. A total of 56 fixed partial dentures (FPDs) and a total of 149 screw-shaped, and self-tapping implants (Astra Tech implants) -- 83 in the maxilla and 66 in the mandible -- were installed in a two-stage procedure. Each patient received a minimum of two implants and by randomization every second implant that was installed had been designed with a machined surface and the remaining with a roughened Tioblast surface. Abutment connection was performed 3-6 months after implant installation. Clinical and radiographical examinations were performed following FPD connection and once a year during a 5-year follow-up period. The analysis of peri-implant bone-level alterations was performed on subject, FPD and implant levels. Four patients and four FPDs were lost to the 5 years of monitoring. One implant (machined surface) did not properly integrate (early failure), and was removed at the time of abutment connection. Three implants were lost during function and a further eight implants could not be accounted for at the 5-year follow-up examination. The overall failure rate at 5 years was 5.9% (subject level), 5.3% (FPD level) and 2.7% (implant level). Radiographic signs of loss of osseointegration were not found at any of the implants during the 5-year observation period. During the first year in function there was on average 0.33 (SD, 0.61) mm loss of peri-implant marginal bone on the subject and FPD levels and 0.31 (0.81) mm on the implant level. During the subsequent 4 years, the peri-implant bone-level alterations were small. The calculated annual change in peri-implant bone level was -0.02 (0.15) on subject and FPD levels and -0.03 (0.20) on the implant level. Thus, the mean total bone-level change over the 5-year interval amounted to 0.41 mm on all three levels of analysis. In the interval between baseline and 5 years, the machined and the Tioblast implants lost on average 0.33 and 0.48 mm, respectively (p>0.05). The present randomized, controlled clinical trial that included partially edentulous periodontitis-susceptible subjects demonstrated that bone loss (i) during the first year of function as well as annually thereafter was small and (ii) did not vary between implants with machined- or rough-surface designs.


[Autotransfusions of sorbent blood in treating peptic ulcer patients with an unfavorable course].
Autotransfusion of sorbent blood was used in the complex treatment of 62 patients with gastric ulcer characterized by an unfavourable course. The course of autotransfusions favoured scarring of the gastric ulcer in 70.9% of patients, normalized the helper/suppressor relations of regulatory subpopulations of T-lymphocytes, normalized the indices of natural killer activity.


The High Temperature Tensile and Creep Behaviors of High Entropy Superalloy.
This article presents the high temperature tensile and creep behaviors of a novel high entropy alloy (HEA). The microstructure of this HEA resembles that of advanced superalloys with a high entropy FCC matrix and L12 ordered precipitates, so it is also named as "high entropy superalloy (HESA)". The tensile yield strengths of HESA surpass those of the reported HEAs from room temperature to elevated temperatures; furthermore, its creep resistance at 982 °C can be compared to those of some Ni-based superalloys. Analysis on experimental results indicate that HESA could be strengthened by the low stacking-fault energy of the matrix, high anti-phase boundary energy of the strengthening precipitate, and thermally stable microstructure. Positive misfit between FCC matrix and precipitate has yielded parallel raft microstructure during creep at 982 °C, and the creep curves of HESA were dominated by tertiary creep behavior. To the best of authors' knowledge, this article is the first to present the elevated temperature tensile creep study on full scale specimens of a high entropy alloy, and the potential of HESA for high temperature structural application is discussed.


Novel canine bocavirus strain associated with severe enteritis in a dog litter.
Bocaviruses are small non-enveloped viruses with a linear ssDNA genome, that belong to the genus Bocaparvovirus of the subfamiliy Parvovirinae. Bocavirus infections are associated with a wide spectrum of disease in humans and various mammalian species. Here we describe a fatal enteritis associated with infection with a novel strain of canine bocavirus 2 (CaBoV-2), that occurred in a litter of German wirehaired pointers. Necropsy performed on three puppies revealed an enteritis reminiscent of canine parvovirus associated enteritis, accompanied with signs of lymphocytolytic disease in bone marrow, spleen, lymph nodes and thymus. While other major causes of enteritis of young dogs, including canine parvovirus, were excluded, by random PCR in combination with next-generation sequencing, a novel CaBoV-2 strain was detected. Phylogenetic analysis of the genome of this novel canine bocavirus strain indicated that this virus was indeed most closely related to group 2 canine bocaviruses. Infection with canine bocavirus was confirmed by in situ hybridization, which revealed the presence of CaBoV-2 nucleic acid in the intestinal tract and lymphoid tissues of the dogs. In a small-scale retrospective analysis concerning the role of CaBoV-2 no additional cases were identified. The findings of this study provide novel insights into the pathogenicity of canine bocaviruses.


Formulating tightest bounds on causal effects in studies with unmeasured confounders.
This paper considers the problem of evaluating the causal effect of an exposure on an outcome in observational studies with both measured and unmeasured confounders between the exposure and the outcome. Under such a situation, MacLehose et al. (Epidemiology 2005; 16:548-555) applied linear programming optimization software to find the minimum and maximum possible values of the causal effect for specific numerical data. In this paper, we apply the symbolic Balke-Pearl linear programming method (Probabilistic counterfactuals: semantics, computation, and applications. Ph.D. Thesis, UCLA Cognitive Systems Laboratory, 1995; J. Amer. Statist. Assoc. 1997; 92:1172-1176) to derive the simple closed-form expressions for the lower and upper bounds on causal effects under various assumptions of monotonicity. These universal bounds enable epidemiologists and medical researchers to assess causal effects from observed data with minimum computational effort, and they further shed light on the accuracy of the assessment.


Homozygous mutation of PLCZ1 leads to defective human oocyte activation and infertility that is not rescued by the WW-binding protein PAWP.
In mammals, sperm-oocyte fusion initiates Ca(2+) oscillations leading to a series of events called oocyte activation, which is the first stage of embryo development. Ca(2+) signaling is elicited by the delivery of an oocyte-activating factor by the sperm. A sperm-specific phospholipase C (PLCZ1) has emerged as the likely candidate to induce oocyte activation. Recently, PAWP, a sperm-born tryptophan domain-binding protein coded by WBP2NL, was proposed to serve the same purpose. Here, we studied two infertile brothers exhibiting normal sperm morphology but complete fertilization failure after intracytoplasmic sperm injection. Whole exomic sequencing evidenced a missense homozygous mutation in PLCZ1, c.1465A>T; p.Ile489Phe, converting Ile 489 into Phe. We showed the mutation is deleterious, leading to the absence of the protein in sperm, mislocalization of the protein when injected in mouse GV and MII oocytes, highly abnormal Ca(2+) transients and early embryonic arrest. Altogether these alterations are consistent with our patients' sperm inability to induce oocyte activation and initiate embryo development. In contrast, no deleterious variants were identified in WBP2NL and PAWP presented normal expression and localization. Overall we demonstrate in humans, the absence of PLCZ1 alone is sufficient to prevent oocyte activation irrespective of the presence of PAWP. Additionally, it is the first mutation located in the C2 domain of PLCZ1, a domain involved in targeting proteins to cell membranes. This opens the door to structure-function studies to identify the conserved amino acids of the C2 domain that regulate the targeting of PLCZ1 and its selectivity for its lipid substrate(s).


Degeneration in Arousal Neurons in Chronic Sleep Disruption Modeling Sleep Apnea.
Chronic sleep disruption (CSD) is a cardinal feature of sleep apnea that predicts impaired wakefulness. Despite effective treatment of apneas and sleep disruption, patients with sleep apnea may have persistent somnolence. Lasting wake disturbances in treated sleep apnea raise the possibility that CSD may induce sufficient degeneration in wake-activated neurons (WAN) to cause irreversible wake impairments. Implementing a stereological approach in a murine model of CSD, we found reduced neuronal counts in representative WAN groups, locus coeruleus (LC) and orexinergic neurons, reduced by 50 and 25%, respectively. Mice exposed to CSD showed shortened sleep latencies lasting at least 4 weeks into recovery from CSD. As CSD results in frequent activation of WAN, we hypothesized that CSD promotes mitochondrial metabolic stress in WAN. In support, CSD increased lipofuscin within select WAN. Further, examining the LC as a representative WAN nucleus, we observed increased mitochondrial protein acetylation and down-regulation of anti-oxidant enzyme and brain-derived neurotrophic factor mRNA. Remarkably, CSD markedly increased tumor necrosis factor-alpha within WAN, and not in adjacent neurons or glia. Thus, CSD, as observed in sleep apnea, results in a composite of lasting wake impairments, loss of select neurons, a pro-inflammatory, pro-oxidative mitochondrial stress response in WAN, consistent with a degenerative process with behavioral consequences.


fbl-Typing of Staphylococcus lugdunensis: A Frontline Tool for Epidemiological Studies, but Not Predictive of Fibrinogen Binding Ability.
Staphylococcus lugdunensis is increasingly recognized as a potent pathogen, responsible for severe infections with an outcome resembling that of Staphylococcus aureus. Here, we developed and evaluated a tool for S. lugdunensis typing, using DNA sequence analysis of the repeat-encoding region (R-domain) in the gene encoding the fibrinogen (Fg)-binding protein Fbl (fbl-typing). We typed 240 S. lugdunensis isolates from various clinical and geographical origins. The length of the R-domain ranged from 9 to 52 repeats. fbl-typing identified 54 unique 18-bp repeat sequences and 92 distinct fbl-types. The discriminatory power of fbl-typing was higher than that of multilocus sequence typing (MLST) and equivalent to that of tandem repeat sequence typing. fbl-types could assign isolates to MLST clonal complexes with excellent predictive power. The ability to promote adherence to immobilized human Fg was evaluated for 55 isolates chosen to reflect the genetic diversity of the fbl gene. We observed no direct correlation between Fg binding ability and fbl-types. However, the lowest percentage of Fg binding was observed for isolates carrying a 5'-end frameshift mutation of the fbl gene and for those harboring fewer than 43 repeats in the R-domain. qRT-PCR assays for some isolates revealed no correlation between fbl gene expression and Fg binding capacity. In conclusion, this study shows that fbl-typing is a useful tool in S. lugdunensis epidemiology, especially because it is an easy, cost-effective, rapid and portable method (http://fbl-typing.univ-rouen.fr/). The impact of fbl polymorphism on the structure of the protein, its expression on the cell surface and in virulence remains to be determined.


Topical polidocanol application in combination with static stretching in tendinopathies: a prospective pilot study.
Highly operator-based injection therapy with vasosclerosing and anesthetic polidocanol is used for tendinopathies. This pilot-study evaluates the topical application of polidocanol gel. Prospective case series. 39 patients with tendinopathies (14 Achilles, 14 patella, 11 wrist extensors) with a symptom duration > 6 months were included. Polidocanol and static stretching were the therapy in the first 2 weeks, while static stretching was continuously performed for 6 months. Clinical outcome was evaluated with VISA-A, VISA-P and DASH Scores and sonographically with B-Mode (B-Mode), Power Doppler (PD) and Shearwave Elastography (SWE). 22 patients clinically improved (>+10 score points), 11 patients were without improvement (<+ 10) and 1 patient worsened during 6 months. The VISA-A Score increased in average 19 points from 56 to 75 (p< 0.01), VISA-P Score increased 13 points from 59 to 72 (p< 0,01) and the DASH-Score decreased 20 points from 40 to 20 (p< 0,01). SWE correlates better than B-Mode or PD with symptom improvement. The combination of static training and topical polidocanol application seems to be successful in the treatment of tendinopathies. Further RCT studies need to evaluate the efficiency of topical polidocanol application. SWE is a more sensitive tool to describe symptom development than PD or B-Mode. IV.


Federated Learning-Based Spectrum Occupancy Detection.
Dynamic access to the spectrum is essential for radiocommunication and its limited spectrum resources. The key element of dynamic spectrum access systems is most often effective spectrum occupancy detection. In many cases, machine learning algorithms improve this detection's effectiveness. Given the recent trend of using federated learning, we present a federated learning algorithm for distributed spectrum occupancy detection. This idea improves overall spectrum-detection effectiveness, simultaneously keeping a low amount of data that needs to be exchanged between sensors. The proposed solution achieves a higher accuracy score than separate and autonomous models used without federated learning. Additionally, the proposed solution shows some sort of resistance to faulty sensors encountered in the system. The results of the work presented in the article are based on actual signal samples collected in the laboratory. The proposed algorithm is effective (in terms of spectrum occupancy detection and amount of exchanged data), especially in the context of a set of sensors in which there are faulty sensors.


How are nitrogen availability, fine-root mass, and nitrogen uptake related empirically? Implications for models and theory.
Understanding the effects of global change in terrestrial communities requires an understanding of how limiting resources interact with plant traits to affect productivity. Here, we focus on nitrogen and ask whether plant community nitrogen uptake rate is determined (a) by nitrogen availability alone or (b) by the product of nitrogen availability and fine-root mass. Surprisingly, this is not empirically resolved. We performed controlled microcosm experiments and reanalyzed published pot experiments and field data to determine the relationship between community-level nitrogen uptake rate, nitrogen availability, and fine-root mass for 46 unique combinations of species, nitrogen levels, and growing conditions. We found that plant community nitrogen uptake rate was unaffected by fine-root mass in 63% of cases and saturated with fine-root mass in 29% of cases (92% in total). In contrast, plant community nitrogen uptake rate was clearly affected by nitrogen availability. The results support the idea that although plants may over-proliferate fine roots for individual-level competition, it comes without an increase in community-level nitrogen uptake. The results have implications for the mechanisms included in coupled carbon-nitrogen terrestrial biosphere models (CN-TBMs) and are consistent with CN-TBMs that operate above the individual scale and omit fine-root mass in equations of nitrogen uptake rate but inconsistent with the majority of CN-TBMs, which operate above the individual scale and include fine-root mass in equations of nitrogen uptake rate. For the much smaller number of CN-TBMs that explicitly model individual-based belowground competition for nitrogen, the results suggest that the relative (not absolute) fine-root mass of competing individuals should be included in the equations that determine individual-level nitrogen uptake rates. By providing empirical data to support the assumptions used in CN-TBMs, we put their global climate change predictions on firmer ground.