Is there a role for erythropoietin in cardiovascular disease?
Despite the advances in the cardiovascular field, cardiovascular diseases remain an important health problem with a high mortality rate. Novel therapeutic attempts that target myocardial ischemia and heart failure offer attractive adjuncts and/or alternatives to commonly employed regimens. The development of novel laboratory technologies over the last decade has led to substantial progress in bringing new therapies to the bedside. Current experimental and clinical trials in the use of erythropoietin (EPO) in cardiovascular diseases are reviewed. This review will widen knowledge of the therapeutic potential of EPO's non-erythropoietic beneficial effects in a clinical cardiovascular setting. Results from preclinical trials regarding the non-erythropoietic effects of erythropoietin are really encouraging. Further clinical studies are warranted to define the beneficial role of EPO in the clinical setting of coronary artery disease, heart failure and peripheral artery disease.


Role of the type 1 TNF receptor in lung inflammation after inhalation of endotoxin or Pseudomonas aeruginosa.
To determine the roles of the type 1 tumor necrosis factor (TNF) receptor (TNFR1) in lung inflammation and antibacterial defense, we exposed transgenic mice lacking TNFR1 [TNFR1(-/-)] and wild-type control mice to aerosolized lipopolysaccharide or Pseudomonas aeruginosa. After LPS, bronchoalveolar lavage fluid (BALF) from TNFR1(-/-) mice contained fewer neutrophils and less macrophage inflammatory protein-2 than BALF from control mice. TNF-alpha, interleukin-1beta, and total protein levels in BALF as well as tissue intercellular adhesion molecule-1 expression did not differ between the two groups. In contrast, lung inflammation and bacterial clearance after infection were augmented in TNFR1(-/-) mice. BALF from infected TNFR1(-/-) mice contained more neutrophils and TNF-alpha and less interleukin-1beta and macrophage inflammatory protein-2 than that from control mice, but protein levels were similarly elevated in both groups. Lung inflammation and bacterial clearance were also augmented in mice lacking both TNF receptors. Thus TNFR1 facilitates neutrophil recruitment after inhalation of lipopolysaccharide, in part by augmenting chemokine induction. In contrast, TNFR1 attenuates lung inflammation in response to live bacteria but does not contribute to increased lung permeability and is not required for the elimination of P. aeruginosa.


Ceftriaxone treatment affects the levels of GLT1 and ENT1 as well as ethanol intake in alcohol-preferring rats.
Studies have demonstrated that deletion of equilibrative nucleoside transporter 1 (ENT1) is associated with reduced glutamate transporter 1 (GLT1) level, and consequently increased ethanol intake. In this study, we measured changes in GLT1 and ENT1 levels in prefrontal cortex (PFC), and nucleus accumbens (NAc) core and shell associated with alcohol drinking in alcohol-preferring (P) rats. We examined, then, whether ceftriaxone (CEF) would affect both GLT1 and ENT1 levels in these brain regions. P rats were given 24-h concurrent access to 15 and 30% ethanol, water, and food for 5 weeks. On Week 6, P rats received 100 mg/kg CEF (i.p.) or a saline vehicle for five consecutive days. Ethanol intake was measured daily for 8 days starting on the first day of injections. We found a significant reduction in daily ethanol intake in CEF-treated group, starting on Day 2 of injections. Western blot for GLT1 and binding assay for ENT1 revealed downregulation of GLT1 level, whereas ENT1 levels were increased in the NAc core and NAc shell, respectively, but not in the PFC in saline vehicle group. Importantly, CEF treatment reversed these effects in both NAc core and shell. These findings provide evidence for potential regulatory effects of CEF on both GLT1 and ENT1 expression in reducing ethanol intake.


Remodeling of axonal connections contributes to recovery in an animal model of multiple sclerosis.
In multiple sclerosis (MS), inflammation in the central nervous system (CNS) leads to damage of axons and myelin. Early during the clinical course, patients can compensate this damage, but little is known about the changes that underlie this improvement of neurological function. To study axonal changes that may contribute to recovery, we made use of an animal model of MS, which allows us to target inflammatory lesions to the corticospinal tract (CST), a major descending motor pathway. We demonstrate that axons remodel at multiple levels in response to a single neuroinflammatory lesion as follows: (a) surrounding the lesion, local interneurons show regenerative sprouting; (b) above the lesion, descending CST axons extend new collaterals that establish a "detour" circuit to the lumbar target area, whereas below the lesion, spared CST axons increase their terminal branching; and (c) in the motor cortex, the distribution of projection neurons is remodeled, and new neurons are recruited to the cortical motor pool. Behavioral tests directly show the importance of these changes for recovery. This paper provides evidence for a highly plastic response of the motor system to a single neuroinflammatory lesion. This framework will help to understand the endogenous repair capacity of the CNS and to develop therapeutic strategies to support it.


Sirtuins and Autophagy in Age-Associated Neurodegenerative Diseases: Lessons from the C. elegans Model.
Age-associated neurodegenerative diseases are known to have "impaired protein clearance" as one of the key features causing their onset and progression. Hence, homeostasis is the key to maintaining balance throughout the cellular system as an organism ages. Any imbalance in the protein clearance machinery is responsible for accumulation of unwanted proteins, leading to pathological consequences-manifesting in neurodegeneration and associated debilitating outcomes. Multiple processes are involved in regulating this phenomenon; however, failure to regulate the autophagic machinery is a critical process that hampers the protein clearing pathway, leading to neurodegeneration. Another important and widely known component that plays a role in modulating neurodegeneration is a class of proteins called sirtuins. These are class III histone deacetylases (HDACs) that are known to regulate various vital processes such as longevity, genomic stability, transcription and DNA repair. These enzymes are also known to modulate neurodegeneration in an autophagy-dependent manner. Considering its genetic relevance and ease of studying disease-related endpoints in neurodegeneration, the model system Caenorhabditis elegans has been successfully employed in deciphering various functional outcomes related to critical protein molecules, cell death pathways and their association with ageing. This review summarizes the vital role of sirtuins and autophagy in ageing and neurodegeneration, in particular highlighting the knowledge obtained using the C. elegans model system.


New daily persistent headache.
New daily persistent headache (NDPH) is a unique form of chronic daily headache (CDH) which is marked by a daily headache from onset, typically occurring in individuals without a significant prior history of headaches. There are two subforms of NDPH: one which is self-limited and normally goes away without therapy, and a more chronic refractory form which is unresponsive to typical headache treatment strategies. The pathogenesis of NDPH is unknown but recent observations suggest a connection with cervical spine hypermobility and elevation of proinflammatory cytokines in the cerebrospinal fluid (CSF). Recognized triggers for NDPH include infection, stressful life events, and surgical procedures. Clinically, NDPH is characterized by continuous head pain of mild to severe intensity. Migrainous symptoms are common. The syndrome appears to affect women in their teens and 20s, while males develop NDPH later in life in their 50s or 60s. There are no recognized treatments for this condition, although treatment options will be discussed. Secondary mimics of NDPH will also be touched upon in this chapter.


[Superficial temporal venous drainage and its risks. Surgical implications].
Certain failures in scalp surgery due to defective venous drainage have led the authors to reconsider the classical anatomical data concerning the temporofrontal venous network. The study conducted in the anatomy laboratory concerned 110 superficial temporal territories injected with various coloured polymerizable substances in order to visualize this network in the skin. This study enabled the authors to describe nine types of venous drainage, the surgical implications of which are discussed.


Hepcidin-25: Measurement by LC-MS/MS in serum and urine, reference ranges and urinary fractional excretion.
A liquid chromatography tandem-mass spectrometry (LC-MS/MS) method was developed for reliably quantifying hepcidin-25 in human urine and serum. A 95% reference range was established for serum hepcidin-25 levels by standardizing the sampling time between 8:00am and 11:00am in 90 apparently healthy volunteers. The association between hepcidin-25 concentration and other biological parameters was studied using multivariable analysis and the coefficient of renal excretion of hepcidin-25 was calculated. Preanalytical variables were also investigated. The LC-MS/MS method was validated using a recent validation strategy based on accuracy profiles. Good results were obtained in terms of trueness, precision, and linearity in the following dosing ranges: from 0.77 to 200nmol/L for urine and from 0.48 to 100nmol/L for serum. The 95% reference range of serum hepcidin-25 concentration established after excluding known conditions that affect hepcidin-25 expression was 1.5 to 15.2nmol/L. A difference between genders was demonstrated with a median concentration of 5.5 versus 7.2nmol/L for women and men, respectively. Serum hepcidin-25 concentrations were strongly correlated with ferritin and, to a lesser extent, with iron levels. The coefficient of renal excretion ranged from 0.1 to 16.4%. Higher values of hepcidin-25 concentrations were observed on ethylene diamine tetraacetate tubes compared to serum or lithium-heparin devices.


Pharmacology and biological efficacy of a recombinant, humanized, single-chain antibody C5 complement inhibitor in patients undergoing coronary artery bypass graft surgery with cardiopulmonary bypass.
Cardiopulmonary bypass (CPB) induces a systemic inflammatory response that causes substantial clinical morbidity. Activation of complement during CPB contributes significantly to this inflammatory process. We examined the capability of a novel therapeutic complement inhibitor to prevent pathological complement activation and tissue injury in patients undergoing CPB. A humanized, recombinant, single-chain antibody specific for human C5, h5G1.1-scFv, was intravenously administered in 1 of 4 doses ranging from 0.2 to 2.0 mg/kg before CPB. h5G1.1-scFv was found to be safe and well tolerated. Pharmacokinetic analysis revealed a sustained half-life from 7.0 to 14.5 hours. Pharmacodynamic analysis demonstrated significant dose-dependent inhibition of complement hemolytic activity for up to 14 hours at 2 mg/kg. The generation of proinflammatory complement byproducts (sC5b-9) was effectively inhibited in a dose-dependent fashion. Leukocyte activation, as measured by surface expression of CD11b, was reduced (P<0.05) in patients who received 1 and 2 mg/kg. There was a 40% reduction in myocardial injury (creatine kinase-MB release, P=0.05) in patients who received 2 mg/kg. Sequential Mini-Mental State Examinations (MMSE) demonstrated an 80% reduction in new cognitive deficits (P<0.05) in patients treated with 2 mg/kg. Finally, there was a 1-U reduction in postoperative blood loss (P<0. 05) in patients who received 1 or 2 mg/kg. A single-chain antibody specific for human C5 is a safe and effective inhibitor of pathological complement activation in patients undergoing CPB. In addition to significantly reducing sC5b-9 formation and leukocyte CD11b expression, C5 inhibition significantly attenuates postoperative myocardial injury, cognitive deficits, and blood loss. These data suggest that C5 inhibition may represent a novel therapeutic strategy for preventing complement-mediated inflammation and tissue injury.


Low Childhood Cholesterol Absorption Predisposes to Gallstone Disease: The Cardiovascular Risk in Young Finns Study.
Unraveling pathogenesis of gallstones could help to diminish its enormous disease burden. We hypothesized that certain properties of childhood cholesterol metabolism predict gallstone disease in adulthood. Childhood serum cholestanol and plant sterols (surrogates for cholesterol absorption), cholesterol precursors (surrogates for cholesterol synthesis), lipids, demographics, and dietary habits were compared between individuals diagnosed with gallstone disease subsequently in adulthood (n = 95) and control subjects (n = 190) matched for age, sex, and body mass index in 1980. Subjects were participants of prospective Cardiovascular Risk in Young Finns Study. In 1980, at mean age of 11.4 years gallstone cohort was characterized by 5.8% lower cholestanol (P = 0.038), and 11.2% to 12.2% (P range = 0.003-0.008) lower plant sterols campesterol, sitosterol, and avenasterol compared with controls. Mean lathosterol/sitosterol ratio was 16.3% higher in gallstone compared with control cohort (P = 0.028). Female gallstone group had 5.4% lower mean cholestanol compared with controls (P < 0.05), and, respectively, those of campesterol, sitosterol, and avenasterol were 12.7% to 14.0% lower (P < 0.05 for each). Body mass index was inversely related to cholestanol and sitosterol (r range = -0.161 to -0.208, P < 0.05 for each) in controls, but not among patients with gallstone. In whole study population, surrogates of cholesterol absorption (eg, campesterol, P = 0.018) and low dietary intake of vegetables (P = 0.009) were significant predictors of gallstones in logistic regression model. Cholesterol metabolism trait characterized by low serum levels of surrogate markers of cholesterol absorption precedes adult gallstone disease already in childhood. Low serum cholestanol and plant sterol ratios during normal Western diet may have role as predictive biomarkers for gallstones.


Disruption of six unknown open reading frames from Saccharomyces cerevisiae reveals two genes involved in vacuolar morphogenesis and one gene required for sporulation.
In this report we describe the construction and basic phenotypic analysis of deletion mutants in six open reading frames (ORFs) of unknown function from the yeast Saccharomyces cerevisiae. Using the dominant kanMX marker and polymerase chain reaction (PCR) methods, deletion cassettes were constructed for five ORFs (YNL099c, YNL100w, YNL101w, YNL106c and YNL242w) located on chromosome XIV and one ORF (YOR109w) located on chromosome XV. The recovery of viable haploid deletant strains among the meiotic products of heterozygous deletants for each ORF demonstrated that none of the analysed ORFs was essential. With the exception of YNL242w, no alterations in growth characteristics or mating and sporulation efficiencies associated with deletion of the ORFs were observed. Homozygous diploid ynl242w delta cells obtained in three different genetic backgrounds were unable to sporulate, indicating that the product of this ORF is required for sporulation. Complementation of the sporulation defect by the cognate gene clone confirmed this observation. YNL106c and YOR109w are very similar and show strong sequence homology with a mammalian phosphatidylinositol-phosphate 5-phosphatase, synaptojanin, known to be involved in synaptic vesicle cycling. Strains bearing single and double deletions of YNL106c and YOR109w were seen to display abnormal vacuolar morphologies of varying degrees. Complementation tests indicated that YNL106c and YOR109w are redundant genes.


The Fifth International Survey of Critical Care Nursing Organizations: Implications for Policy.
To examine the activities, concerns, and expectations of critical care nurses and professional critical care nursing organizations worldwide. A descriptive survey methodology was used. This study is the fifth worldwide quadrennial review of its type to monitor variations in critical care nursing needs and provide robust evidence to inform policy related to critical care nursing practice. The fifth World Federation of Critical Care Nurses international survey of critical care nursing organizations was emailed to potential participants from countries with critical care nursing organizations or known critical care nurse leaders. Data were collected online. Responses were entered into SPSS version 23 software (IBM Corp., Armonk, NY, USA) and analyzed by geographical region and national wealth group. Eighty-two national representative respondents participated in the survey, of whom two thirds (n = 56, 68%) had an established critical care nursing organization in their country. The five most important issues identified were working conditions, teamwork, staffing levels, the need for formal practice guidelines and competencies, and wages. The top five critical care nursing organization services that were considered to be of most importance were professional representation, as well as provision of workshops and education forums, national conferences, practice standards and guidelines, and local conferences. The most important contributions expected from the World Federation of Critical Care Nurses were standards for clinical practice and professional practice, international conferences, professional representation, and study and education grants. The results highlight priority areas for critical care nursing and reinforce the need to address factors that can inform critical care nursing policy and practice. Results of this survey should be incorporated into strategic action plans at the national and international levels. Nursing leaders, policymakers, and other interested stakeholders should consider these findings when planning critical care workforce requirements. Interested parties should work collaboratively to inform recommendations for further policy and action.


Toxic effect of nickel on hemoglobin concentration of Limnodrilus hoffmeisteri in spiked sediments of trout farms.
Toxicity and uptake data for Limnodrilus hoffmeisteri generated by nickel in systems using three natural sediments (trout farms: El Oyamel, El Truchón, and El Potrero), are presented. Nickel uptake and hemoglobin concentration were studied in L. hoffmeisteri exposed to spiked sediments. Nickel concentration and its toxic effect on hemoglobin were used as indicators of exposure. Sediment texture was also considered. Hemoglobin concentration decreased after treatment with nickel. The hemoglobin concentration test indicated a response to the bioavailability of nickel. This investigation clearly documents that sediments of El Truchón, El Oyamel, and El Potrero exhibit a toxicity potential. These results suggest the usefulness of diversity of bioassays for evaluating the toxicity of sediments polluted with heavy metals.


Primary structure of the murine monoclonal IgG2a antibody mAb735 against alpha(2-8) polysialic acid. 1) Amino-acid sequence of the light (L-) chain, kappa-isotype.
Here we report the complete amino-acid sequence of the anti-alpha(2-8)polysialic acid antibody mAb735 light chain. The sequence was determined after digestion of the reduced and carboxymethylated L-chain with trypsin, SV-8 proteinase, and Asp-N proteinase, isolation of the generated peptides by RP-HPLC and characterization of these fragments by sequence analysis, amino-acid analysis and/or plasma desorption mass spectrometry. According to Kabat et al. the variable region belongs to the V kappa-II subgroup, whilst according to Hum et al. it belongs to the V kappa-1B subgroup. With the exception of proline at position 46, the sequence from position 1 to 95 is identical to the translated DNA sequence of a V kappa-germline gene segment previously reported.


In context: physician-patient communication and managed care.
Communication between a physician and his or her patient is a critical component of medical care delivery. The quality of communication affects patient satisfaction and health outcomes. Managed care has heightened the awareness of communication because of the direct links among communication, outcomes, and malpractice liability. This article describes patient satisfaction, the relationship between communication and biological outcomes, the role that communication plays in malpractice prevention, the communication challenges present in the managed health care environment, and the need for communication skills training.


The effect of remifentanil on the incidence of agitation on emergence from sevoflurane anaesthesia in children undergoing adenotonsillectomy.
The aim of the present study was to assess the effect of remifentanil on the incidence of emergence agitation in preschool-aged children undergoing adenotonsillectomy with sevoflurane anaesthesia. Sixty children, aged three to seven years, American Society of Anesthesiologists physical status I or II, were randomised into either group S (sevoflurane alone, n=30) or group R (sevoflurane plus remifentanil, n=30). Anaesthesia was induced with an intravenous bolus injection of fentanyl 3 microg/kg and propofol 2.5 mg/kg. Endotracheal intubation was facilitated by vecuronium 0.1 mg/kg. All patients were ventilated with 50% nitrous oxide and 1.5 to 2.5% sevoflurane in oxygen. End-tidal CO2 was maintained at 35 +/- 4 mmHg. Group S received no other medication while group R received remifentanil 1 microg/kg/minute intraoperatively. Mean blood pressure, heart rate, pulse oximetry, eye-opening time and extubation time were recorded in the operating room. In recovery, emergence agitation was assessed using the Pediatric Anesthesia Emergence Delirium scale with a score > or =10 taken as indicating agitation. Emergence agitation occurred in 20 of the 30 patients in group S and seven of the 30 patients in group R (P < 0.01). In preschool-aged children undergoing adenotonsillectomy with sevoflurane general anaesthesia, after propofol and fentanyl induction, intraoperative remifentanil decreased the incidence of emergence agitation.


Optimizing the error term in direct-method SAD phasing.
The probability formula of the direct-method SAD (single-wavelength anomalous diffraction) phasing proposed by Fan & Gu (1985, Acta Cryst. A41, 280-284) contains an error term which is related to the lack-of-closure error. This error term is used as a weighting function in the phase derivation and in the subsequent calculation of electron-density maps. Previously, there has been a constant in the error term that has had to be determined empirically for each particular case. It has been found that improper choice of the constant often leads to failure of the direct-method SAD phasing. The problem is resolved by introducing a modified error term and a method of automatically tuning the associated scaling factor.


[Health insurance coverage for smoking cessation treatment in Japan: current status and future issues].
In Japan, nicotine dependence treatment service for outpatients at registered medical institutions has been started under health insurance coverage since 2006. The reimbursed treatment program consists of five treatment sessions over 12 week duration. Nicotine patch or varenicline can be prescribed under health insurance coverage during the treatment period. The surveys conducted in 2007 and 2009 have proved the effectiveness of the service. However, the accessibility and utilization of smoking cessation treatment are not sufficient, considering the fact that the percentage of smokers who underwent smoking cessation treatment in Japan remained low compared with other countries. Future challenges call for implementing effective measures to improve the accessibility and utilization of the service, while maintaining a satisfactory level of treatment quality.


Bioinspired Colloidal Photonic Composites: Fabrications and Emerging Applications.
Organisms in nature have evolved unique structural colors and stimuli-responsive functions for camouflage, warning, and communication over millions of years, which are essential to their survival in harsh conditions. Inspired by these characteristics, colloidal photonic composites (CPCs) composed of colloidal photonic crystals embedded in the polymeric matrix are artificially prepared and show great promise in applications. This review focuses on the summary of building blocks, i.e., colloidal particles and polymeric matrices, and constructive strategies from the perspective of designing CPCs with robust performance and specific functionality. Furthermore, their state-of-the-art applications are also discussed, including colorful coatings, anti-counterfeiting, and regulation of photoluminescence, especially in the field of visualized sensing. Finally, current challenges and potential for future developments in this field are discussed. The purpose of this review is not only to clarify the design principle for artificial CPCs but also to serve as a roadmap for the exploration of next-generation photonic materials.


Simultaneous Evaluation of the Preservative Effect of RNAlater on Different Tissues by Biomolecular and Histological Analysis.
A major concern in biomedical research is the quality of biological samples. RNAlater is a stabilizer, which was originally developed for RNA preservation in fresh tissues and is important for collection and transportation. However, this reagent lacks a comprehensive and systematic evaluation of its preservative effect on different mammalian tissues under consistent experimental conditions. In this study, we collected liver, kidney, testis, brain, and colon tissues from mice and divided the samples into the following respective groups: fresh, RNAlater preserved, and liquid nitrogen snap frozen. Biomolecules (RNA, DNA, and protein) were extracted from each tissue in each group, and samples were formalin fixed and paraffin embedded for quality assessment. Our results revealed that high-quality (yield, purity, and integrity) nucleic acids could be extracted from all samples. Gene expression determined by quantitative real-time polymerase chain reaction exhibited no major difference among the three groups. Notably, we observed significant protein degradation in brain tissue preserved by RNAlater compared with fresh and snap-frozen tissue. Protein expression of the other four tissues was similar among the three groups. Hematoxylin and eosin staining of all tissue types indicated no apparent difference among the three groups. We concluded that high-quality nucleic acids can be obtained and tissue morphology conserved when tissues are preserved with RNAlater. However, there are tissue-specific differences in protein preservation when using RNAlater, which should be evaluated before extensive storage.


The potential role of targeted therapies in the management of neuroendocrine tumours.
The management of gastro-entero-pancreatic neuroendocrine tumours is evolving thanks to new TNM-classification, diagnostic and staging procedures and new therapeutic options. Targeting new pathways, mostly angiogenesis, development of novel agents is under way and opens new perspectives in controlling the evolution of these tumours and possibly changing their management. In parallel, new functional imaging techniques and biomolecular markers will be developed to provide adequate tools for the assessment of tumor response according to therapeutic intervention on angiogenesis, proliferation and apoptosis. This paper reviews the potential role of new investigational targeted agents which will likely become the backbone of future therapy of neuroendocrine tumors.


Ultrasound brachial plexus anesthesia and analgesia for upper extremity surgery: essentials of our current understanding, 2011.
Ultrasound-guidance is gaining tremendous popularity. There is growing evidence of value with emphasis on clinical relevance, but can ultrasound-guidance scientifically warrant changing the practice of upper extremity regional? The literature is searched to describe findings where ultrasound may reduce complication rates, reduce block performance times, and improve block efficacy and quality. Ultrasound examination identified variations in anatomical positioning of C5-C7 roots in approximately half of all patients despite no deleterious effects on block efficacy. Anesthetic volumes in brachial plexus blockade may be reduced without compromise of effectiveness. However, even with reduced volumes injected into the interscalene space, respiratory compromise from effect(s) on the phrenic nerve may result in hemi-diaphragmatic paresis. Ultrasound-guidance may reduce discomfort during axillary block placement compared with neurostimulation or parasthesia. Nerve catheters may be highly effective and provide prolonged analgesia compared with single-shot injections. Infraclavicular catheters result in improved analgesia compared with supraclavicular catheters and multiple injections of local provide no advantage over single-shot infraclavicular blockade. Dexamethasone combined with local may extend analgesia following a single-injection interscalene or supraclavicular block. During interscalene blockade, intraepineurial injections may occur, but incidence of nerve injury remains low. Therefore, debate continues about intraepineurial injections. Intraepineurial injection requires additional investigation. Conclusions have suggested reducing typical volumes (40 ml) of local with ultrasound-directed upper extremity blockade. Increased use of perineural catheters is being advocated for prolonged analgesia, but risk-to-benefit consequences need to always be considered.


Antibiotics in pregnancy--a prospective cohort study on the policy of antibiotic prescription.
Pregnancy is associated with special problems with respect to antibiotic selection and dosage due to potential teratogenic or toxic effects on the fetus by the drug itself, and the great physiological adjustments in the mother. This survey was designed to record the use of antibiotics and the policy of prescription of antimicrobial drugs during the course of pregnancy. In total, 4055 pregnant women residing in a county in south-western Finland during the period June 15, 1987-June 14, 1988 were studied. Penicillin, erythromycin and pivmecillinam were the most often used antibiotics during pregnancy comprising together 65.4% of all antibiotic use; 94.1% of all antimicrobial medication was administered orally. The highest incidence for antibiotic use (45.4% of all) as well as for treated infections (45% of all) was at the second trimester. The duration of medication was commonly 10 days (44.4%, SD 14.6) or 7 days (27.9%, SD 7.7). Penicillin was in a few cases prescribed at increased dosage (25.6%), while erythromycin and amoxicillin were occasionally administered at reduced dosages (30.2% and 42.5%, respectively). The dosages should probably be individualized more often, according to the information available on the pharmacokinetics of specific antibiotics during pregnancy. It may also be possible to reduce the length of antibiotic treatment for UTI.


The extended deep inferior epigastric flap: a case series.
The extended deep inferior epigastric flap is a reliable flap that has been found to be useful in covering difficult wounds in the lower torso, groin, perineum, and thigh regions. The author addresses the indications and outcomes in a series of 7 patients.


A Novel Motion Recognition Method Based on Force Myography of Dynamic Muscle Contractions.
Surface electromyogram-based pattern recognition (sEMG-PR) has been considered as the most promising method to control multifunctional prostheses for decades. However, the commercial applications of sEMG-PR in prosthetic control is still limited due to the ambient noise and impedance variation between electrodes and skin surface. In order to reduce these issues, a force-myography-based pattern recognition method was proposed. In this method, a type of polymer-based flexible film sensors, the piezoelectrets, were used to record the rate of stress change (RSC) signals on the muscle surface of eight able-bodied subjects for six hand motions. Thirteen time domain features and four classification algorithms of linear discriminant analysis (LDA), K-nearest neighbor (KNN), artificial neural network (ANN), and support vector machine (SVM) were adopted to decode the RSC signals of different motion classes. In addition, the optimal feature set, classifier, and analysis window length were investigated systematically. Results showed that the average classification accuracy was 95.5 ± 2.2% by using the feature combination of root mean square (RMS) and waveform length (WL) for the classifier of KNN, and the analysis window length of 300 ms was found to obtain the best classification performance. Moreover, the robustness of the proposed method was investigated, and the classification accuracies were observed above 90% even when the white noise ratio increased to 50%. The work of this study demonstrated the effectiveness of RSC-based pattern recognition method for motion classification, and it would provide an alternative approach for the control of multifunctional prostheses.


Creating new supramolecular materials by architecture of three-dimensional nanocrystal fiber networks.
The architecture of three-dimensional interconnecting self-organized nanofiber networks from separate needlelike crystals of L-DHL (lanosta-8,24-dien-3beta-ol:24,25-dihydrolanosterol = 56:44) in di-isooctylphthalate has been achieved for the first time, on the basis of the completely new concept of branching creation by additives (branching promoters). [In this work, an additive, ethylene/vinyl acetate copolymer (EVACP), is used at a concentration of several 10 ppm.] We demonstrate that this novel technique enables us to produce previously unknown self-supporting supramolecular functional materials with tailormade micro- or nanostructures, possessing significantly modified macroscopic properties, by utilizing materials thus far considered to be "useless". In addition, both the self-organized structure and the properties of the new materials can be fine-tuned by altering the processing conditions. Our results show that the formation of the interconnecting 3D self-organized network structure is controlled by a new mechanism, so-called crystallographic mismatch branching mechanism, as opposed to the conventionally adopted molecular self-assembly mechanism. The principles and criteria for the selection of branching promoters are also discussed from the point of view of molecular structures.


Chiral recognition mechanisms with macrocyclic glycopeptide selectors.
Macrocyclic glycopeptide selectors are naturally occurring antibiotics produced by microorganisms. They were found to be excellent chiral selectors for a wide range of enantiomers, including amino acids. Four selectors are commercialized as chiral stationary phases (CSP) for chromatography. They are ristocetin, teicoplanin, vancomycin, and the teicoplanin aglycone (TAG). The key docking interaction for amino acid recognition was established to be a charge-charge interaction between the anionic carboxylate group of the amino acid and a cationic amine group of the macrocyclic peptidic selector basket. The carbohydrate units are responsible for secondary interactions. However, they hinder somewhat the charge-charge docking interaction. The TAG selector is more effective for amino acid enantioseparations than the other CSPs. The "sugar" units are however useful allowing for chiral recognitions of other analytes, e.g., beta-blockers, not possible with the aglycone. Thermodynamic studies established that normal phase and reversed phase enantioseparations were enthalpy-driven. With polar waterless mobile phases used in the polar ionic mode, some separations were enthalpy-driven and others were entropy-driven. The linear solvation energy method was tentatively used to gain knowledge about the chiral recognition mechanism. It appeared to be a viable approach with neutral molecules but it failed with ionizable solutes. With molecular solutes and the teicoplanin CSP, the study showed a significant role of the surface charge-induced dipole interaction and steric effects. The remarkable complementary enantioselectivity effect observed with the four CSPs is discussed.


Meeting EAT-Lancet Food Consumption, Nutritional, and Environmental Health Standards: A U.S. Case Study across Racial and Ethnic Subgroups.
In 2019, The EAT-Lancet Commission developed criteria to assist policymakers and health care systems worldwide in sustaining natural resources to feed a forecasted 10 billion people through the year 2050. Although American dietary habits and underlying food production practices have a disproportionately negative impact on land, greenhouse gas (GHG), and water resources, there is limited information on how this population can meet the EAT-Lancet criteria. To address this, we measured adherence to an adapted version of the EAT-Lancet diet score criteria in United States (U.S.) populations overall and across racial/ethnic subgroups (i.e., black, Latinx, and white). In addition, we assessed the benefits of adherence in terms of saved environmental resources (i.e., land, GHG, and water). By performing these objectives, we provide vital information for the development of effective intervention strategies in the U.S. with enough refinement to address the human health and environmental implications of marginalized populations. Our results demonstrate that, on average, Americans do not meet EAT-Lancet criteria overall or across racial/ethnic subgroups. Shifting dietary intakes to meet the criteria could reduce environmental degradation between 28% and 38%. Furthermore, these methods can be adapted to other nations for the development of meaningful strategies that address the food, energy, and water challenges of our time.


The Impact of a School-Based Water, Sanitation, and Hygiene Program on Absenteeism, Diarrhea, and Respiratory Infection: A Matched-Control Trial in Mali.
We conducted a matched-control trial in Mali to assess the effectiveness of a comprehensive school-based water, sanitation, and hygiene (WASH) intervention on pupil absence, diarrhea, and respiratory infections. After completion of the intervention, data were collected from 100 beneficiary schools and 100 matched comparison schools in 5-6 sessions over a 14-month period. Data collection included roll calls to assess absenteeism and interviews with a subset of pupils to assess recent absence and disease symptoms. The odds of pupils being absent at roll call were 23% higher in beneficiary schools than in comparison schools (odds ratio [OR]: 1.23, 95% confidence interval [CI]: 1.06, 1.42). The odds of pupils reporting being absent due to diarrhea (OR: 0.73, 95% CI: 0.56, 0.94) or having had diarrhea (OR: 0.71, 95% CI: 0.60, 0.85) or respiratory infection symptoms (OR: 0.75, 95% CI: 0.65, 0.86) in the past week were lower in beneficiary schools compared with comparison schools. We found that a school-based WASH intervention can have a positive effect on reducing rates of illness, as well as absence due to diarrhea. However, we did not find evidence that these health impacts led to a reduction in overall absence. Higher absence rates are less likely attributable to the intervention than the result of an imbalance in unobserved confounders between study groups.


Investigation of EMG parameter for transtibial prosthetic user with flexion and extension of the knee and normal walking gait: A preliminary study.
Electromyography signal has been used widely as input for prosthetic's leg movements. C-Leg, for example, is among the prosthetics devices that use electromyography as the main input. The main challenge facing the industrial party is the position of the electromyography sensor as it is fixed inside the socket. The study aims to investigate the best positional parameter of electromyography for transtibial prosthetic users for the device to be effective in multiple movement activities and compare with normal human muscle's activities. DELSYS Trigno wireless electromyography instrument was used in this study to achieve this aim. Ten non-amputee subjects and two transtibial amputees were involved in this study. The surface electromyography signals were recorded from two anterior and posterior below the knee muscles and above the knee muscles, respectively: tibial anterior and gastrocnemius lateral head as well as rectus femoris and biceps femoris during two activities (flexion and extension of knee joint and gait cycle for normal walking). The result during flexion and extension activities for gastrocnemius lateral head and biceps femoris muscles was found to be more useful for the control subjects, while the tibial anterior and also gastrocnemius lateral head are more active for amputee subjects. Also, during normal walking activity for biceps femoris and gastrocnemius lateral head, it was more useful for the control subjects, while for transtibial amputee subject-1, the rectus femoris was the highest signal of the average normal walking activity (0.0001 V) compared to biceps femoris (0.00007 V), as for transtibial amputee subject-2, the biceps femoris was the highest signals of the average normal walking activity (0.0001 V) compared to rectus femoris (0.00004 V). So, it is difficult to rely entirely on the static positioning of the electromyography sensor within the socket as there is a possibility of the sensor to contact with inactive muscle, which will be a gap in the control, leading to a decrease in the functional efficiency of the powered prostheses.


Burkholderia and Cupriavidus spp. are the preferred symbionts of Mimosa spp. in southern China.
Rhizobia were isolated from invasive Mimosa spp. (M. diplotricha and M. pudica) in Dehong district of the province of Yunnan in subtropical southern China. Almost all of the 98 isolates were β-rhizobia in the genera Burkholderia and Cupriavidus. These strains were analysed for their distribution characteristics together with strains from a previous study from Sishuangbanna. The proportion of nodules containing each β-rhizobial genus varied between Mimosa species, with Cupriavidus being predominant in M. diplotricha nodules (63.3% compared to 36.7% occupation with Burkholderia), but with M. pudica showing a slight preference for Burkholderia over Cupriavidus, with them occupying 56.5% and 43.5% of nodules, respectively. The symbiosis-essential genes nodA and nifH were present in all the Burkholderia and Cupriavidus strains tested, and their phylogenies indicated that these Mimosa symbionts share symbiotic genes with native South American rhizobia. The evolutionary discrepancies among 16S rRNA genes, nodA and nifH of Mimosa spp. symbionts, suggests that the nod and nif genes of β-rhizobia evolved independently.


The isoprostanes: unique bioactive products of lipid peroxidation.
The discovery of IsoPs as products of non-enzymatic lipid peroxidation has opened up new areas of investigation regarding the role of free radicals in human physiology and pathophysiology. The quantification of IsoPs as markers of oxidative stress status appears to be an important advance in our ability to explore the role of free radicals in the pathogenesis of human disease. A drawback related to this, however, has been lack of more facile and less expensive methods than mass spectrometry for the measurement of IsoPs. On the other hand, the recent introduction of immunoassay methods for measurement of IsoPs may alleviate this problem, provided they are specific and reliable. If this is the case, immunoassay methodology will most likely lead to an expansion of the use of measurements of IsoPs to assess oxidative stress status in vivo. Another need in the field of free radical medicine is information regarding the clinical pharmacology of antioxidant agents. Because of the evidence implicating free radicals in the pathogenesis of a number of human diseases, large clinical trials are planned or underway to assess whether antioxidants can either prevent the development or ameliorate the pathology of certain human disorders. However, data regarding the most effective doses and combination of antioxidant agents to use in these clinical trials is lacking. As mentioned previously, administration of antioxidants suppresses the formation of IsoPs, even in normal individuals. Thus, measurement of IsoPs may provide a valuable approach to defining the clinical pharmacology of antioxidants. In addition to being markers of oxidative stress, at least two IsoPs possess potent biological activity. The availability of additional IsoPs in synthetic form should broaden our knowledge concerning the role of these molecules as mediators of oxidant stress. Moreover, information regarding the nature of the receptor(s) that mediate the biological actions of IsoPs will be of considerable importance to the development of specific antagonists or agonists of the biological actions of IsoPs. Despite the fact that considerable information has been obtained since the initial report of the discovery of IsoPs, much remains to be understood about these molecules. With continued research in this area, we believe that much new information will emerge that will open up additional important new areas for future investigation.


Salvage of Unilateral Complete Ear Amputation with Continuous Local Hyperbaric Oxygen, Platelet-Rich Plasma and Polydeoxyribonucleotide without Micro-Revascularization.
In many cases of complete ear amputation, microvascular surgery is required for tissue perfusion and organ survival. However, microvascular reconstruction is not always feasible in the absence of suitable vessels. Here, we present the case of a 76-year-old man who underwent complete amputation of the left ear after a collapse at home because of cardiogenic syncope. He was treated with primary replantation and underwent a postoperative salvage course including continuous local hyperbaric oxygen therapy (HBOT), platelet-rich plasma (PRP) injections, and polydeoxyribonucleotide (PDRN) injections. The ear was almost completely salvaged, with a tiny eschar at the mid-scapha on both the anterior and posterior aspects. This case demonstrates the efficacy of local HBOT with PRP and PDRN injections.


Population dynamics of the constitutive biota of French dry sausages in a pilot-scale ripening chamber.
The population dynamic of constitutive biota on 84 samples belonging to two different types of French fermented dry sausages during the ripening process in a pilot-scale ripening chamber was investigated. Samples were analyzed in three steps of their production: fresh product, first drying stage, and finished product. In addition, 180 strains of lactic acid bacteria were identified using a miniaturized biochemical procedure of characterization. In general, the number of lactic acid bacteria that evolved during the ripening process of French dry sausages increased during the first days of the process after which the number of these organisms remained constant at approximately 8 log CFU/g. Lactobacillus sakei and Pediococcus pentosaceus, bacteria added as starter, were the dominant species. Pediococcus urinaeequi, Pediococcus acidilactici, and particularly Lactobacillus curvatus were also present. Finally, we have to take into account that the controlled conditions of the pilot plant generally contribute to the homogenization of the behavior of the starter biota.


Paternal uniparental disomy of chromosome 14: confirmation of a clinically-recognizable phenotype.
We report on a girl with a dicentric chromosome 14 [45,XX,inv(9)(p11q13),dic(14;14)(p11.1;p11.1)] with paternal uniparental disomy (UPD) for chromosome 14. Clinical findings include severe hypotonia, thoracic dystrophy, diastasis recti, swallowing difficulties with aspiration, developmental delay, and multiple minor anomalies. UPD for chromosome 14 has been documented with paternal UPD much less commonly than with maternal UPD. There have been ten cases of paternal UPD for chromosome 14 and one case of segmental paternal isodisomy of chromosome 14. Many of the findings are nonspecific, but the radiographic rib findings (referred to as the "coat-hanger" sign) are characteristic for this condition. UPD 14 studies should be performed in children thought to have Jeune asphyxiating thoracic dystrophy or other related osteochondrodysplasias when the diagnosis is in question. Our patient and the previously reported cases support a discrete recognizable phenotype for paternal UPD for chromosome 14.


Comparison of effects of an intrapulmonary percussive ventilator to standard aerosol and chest physiotherapy in treatment of cystic fibrosis.
Impaired mucociliary clearance due to defective ion and water transport and the effects of chronic airway infections lead to stasis of secretions and progressive pulmonary damage in patients with cystic fibrosis (CF). Methods to improve removal of tenacious lung secretions in CF patients contribute to slowing the decline in respiratory function. We have evaluated an intrapulmonary percussive ventilator (IPV), which is a device designed to enhance airway clearance and preserve lung function. A previous pilot study by us had determined that the device was acceptable to patients and is safe. We undertook a 6 month parallel comparative trial of the IPV versus standard, manual chest physiotherapy in 16 CF children and adults. No significant differences in spirometric measures, numbers of hospitalizations, use of oral or IV antibiotics, or anthropometric measurements were detected between the standard aerosol/chest physiotherapy group and the IPV group over the duration of the trial. Patient acceptance, as determined by participant survey, was good. The device appeared to be safe and durable. It was concluded that the IPV is as effective as standard aerosol and chest physiotherapy in preserving lung function and anthropometric measures, and there was no difference in the use of antibiotics and hospitalizations.


On the notion of 'software independence' in voting systems.
This paper defines and explores the notion of 'software independence' in voting systems: 'A voting system is software independent if an (undetected) change or error in its software cannot cause an undetectable change or error in an election outcome'. For example, optical scan and some cryptographically based voting systems are software independent. Variations and implications of this definition are explored. It is proposed that software-independent voting systems should be preferred, and software-dependent voting systems should be avoided.An initial version of this paper was prepared for use by the Technical Guidelines Development Committee in their development of the Voluntary Voting System Guidelines, which will specify the requirements that the USA voting systems must meet to receive certification.


Social disadvantage, mental illness and predictors of legal involvement.
The following study evaluates the complex association between legal involvement and mental illness. It describes a population of consumers of community mental health programs, comparing those with legal involvement to those without legal involvement, on a number of demographic, clinical and social indicators. It is a secondary analysis of data collected in studies making up the Community Mental Health Evaluation Initiative (CMHEI) in the province of Ontario, Canada. Legal involvement was a significant issue among community mental health program consumers; about one in five consumers had at least some contact with the legal system in the preceding nine months. Legally involved consumers were more likely to be in receipt of social assistance and be unstably housed than those legally uninvolved. However, there were no significant differences between legally involved and uninvolved consumers with respect to severity of symptomatology, current medication use or number of hospitalization days in the past 9 months. A predictive model compared the differential impact of clinical and social determinants upon legal involvement. Analyses failed to uncover a significant relationship between severity of psychiatric symptomatology and legal involvement. Significant predictors of legal involvement included gender, race, drug use as well as housing instability, and receipt of social assistance. Legal involvement was attributable to factors other than the severity of mental illness; these results challenge assumptions that the most symptomatically severe consumers are most at risk of legal involvement. Accordingly, the rate of legal involvement in a sample of community mental health program users must be considered in a broad context, with particular emphasis on social disadvantage.


Delayed chromosomal instability induced by DNA damage.
DNA damage induced by ionizing radiation can result in gene mutation, gene amplification, chromosome rearrangements, cellular transformation, and cell death. Although many of these changes may be induced directly by the radiation, there is accumulating evidence for delayed genomic instability following X-ray exposure. We have investigated this phenomenon by studying delayed chromosomal instability in a hamster-human hybrid cell line by means of fluorescence in situ hybridization. We examined populations of metaphase cells several generations after expanding single-cell colonies that had survived 5 or 10 Gy of X rays. Delayed chromosomal instability, manifested as multiple rearrangements of human chromosome 4 in a background of hamster chromosomes, was observed in 29% of colonies surviving 5 Gy and in 62% of colonies surviving 10 Gy. A correlation of delayed chromosomal instability with delayed reproductive cell death, manifested as reduced plating efficiency in surviving clones, suggests a role for chromosome rearrangements in cytotoxicity. There were small differences in chromosome destabilization and plating efficiencies between cells irradiated with 5 or 10 Gy of X rays after a previous exposure to 10 Gy and cells irradiated only once. Cell clones showing delayed chromosomal instability had normal frequencies of sister chromatid exchange formation, indicating that at this cytogenetic endpoint the chromosomal instability was not apparent. The types of chromosomal rearrangements observed suggest that chromosome fusion, followed by bridge breakage and refusion, contributes to the observed delayed chromosomal instability.


Development of poly (1,8 octanediol-co-citrate) and poly (acrylic acid) nanofibrous scaffolds for wound healing applications.
Wound care is one of the leading health care problems in the United States costing billions of dollars yearly. Annually, millions of acute wounds occur due to surgical procedures or traumas such as burns and abrasions, and these wounds can become non-healing due to bacterial infection or underlying pathologies. Current wound care treatments include the use of bioinert constructs combined with topical administration of anti-bacterial agents and growth factors. However, there is a growing need for the development of bioactive wound dressing materials that are able to promote wound healing and the regeneration of healthy tissue. In this work, we evaluate and report the use of a novel electrospun polymeric scaffold consisting of poly (1,8 octanediol-co-citrate) and poly (acrylic acid) for wound healing applications. The scaffold exhibits intrinsic antibacterial activity, hydrogel-like water uptake abilities, and the ability to deliver physiologically relevant concentrations of growth factor. Additionally, the scaffold shows antibacterial function when tested with bacteria relevant to wound healing applications. Biological characterization of the electrospun scaffold shows excellent cellular adhesion, low cytotoxicity, and enhanced proliferation of skin fibroblasts. This work has potential towards the development of novel bioactive scaffolds for prevention of bacterial infiltration into the wound bed and enhanced healing.


Analysis of the NRT2 nitrate transporter family in Arabidopsis. Structure and gene expression.
Nitrate is an essential element for plant growth, both as a primary nutrient in the nitrogen assimilation pathway and as an important signal for plant development. The uptake of nitrate from the soil and its translocation throughout the plant has been the subject of intensive physiological and molecular studies. Using a reverse genetic approach, the AtNRT2.1 gene has been shown to be involved in the inducible component of the high-affinity nitrate transport system in Arabidopsis. The Arabidopsis Genome Initiative has released nearly the whole genome sequence of Arabidopsis, allowing the identification of a small NRT2 multigene family in this species. Thus, we investigated the phylogenetic relationship between NRT2 proteins belonging to several kingdoms and compared the structure of the different members of the Arabidopsis family. We analyzed, by semiquantitative reverse transcriptase-polymerase chain reaction, the expression pattern of each gene depending on plant organ and development or nutritional status, and compared the relative level of each gene by real-time polymerase chain reaction. We also evaluated the significance of each paralog on the basis of the relative levels of gene expression. The results are discussed in relation with distinct roles for the individual members of the AtNRT2 family.


Portal vein evaluation with US: comparison to angiography combined with CT arterial portography.
To compare ultrasound (US) to angiography combined with computed tomography during arterial portography (CTAP) in the preoperative evaluation of the portal vein. Sixty-three consecutive patients being considered for hepatic resection underwent color and spectral Doppler US and angiography with CTAP before surgery. The main, right, and left portal veins were evaluated separately. A total of 187 veins were assessed for encasement, occlusion, or thrombosis. At surgery, 41 portal veins were abnormal. US allowed detection of 38 of 41 (93%) involved portal veins with 93% sensitivity, 99% specificity, 97% positive predictive value, and 98% negative predictive value. Angiography with CTAP allowed diagnosis of 37 of 41 (90%) involved portal veins with 90% sensitivity, 99% specificity, 95% positive predictive value, and 97% negative predictive value. US is comparable to angiography combined with CTAP in evaluation of the portal vein.


Working conditions and mental health: Results from the CARESUN study.
The authors conducted a work-related stress surveillance study in 2013 on 6,558 public-sector employees in Italy, examining how they perceived their jobs, via the Job Content Questionnaire, and their mental health status, via the General Health Questionnaire 12 (GHQ-12). Of the 2,094 employees completing the questionnaires, 60% were male, 52% had a medium-level education, and 76% had a medium-level job. Three hundred and eighty-five employees (18%) had a GHQ-12 score >3 and were classified as GHQ-12 cases: these were more often female (54%), medium-to-highly educated (54%), and had more often reported health problems over the previous year (51%). Thus, GHQ-12 cases represented a significant percentage of the examined population, indicating that work-related stress surveillance programs are needed for the planning of psychosocial interventions aimed at the reintegration of individuals with mental health problems.


Positive inotropic and sustained anti-beta-adrenergic effect of diadenosine pentaphosphate in human and guinea pig hearts. Role of dinucleotide receptors and adenosine receptors.
Diadenosine polyphosphates are present intracellularly and in extracellular fluid due to release from secretory vesicles in platelets, chromaffin cells and other cells. This study investigates effects of diadenosine pentaphosphate (AP5A) on heart muscle function. Contractile force amplitude and action potential duration at 90% repolarization (APD90) were measured after challenge with AP5A 50 microm or isoproterenol 50-70 nM in guinea pig papillary muscles. Isoproterenol was given immediately after AP5A-exposure or after 45 min washout. AP5A was combined with antagonists to the purinergic P2 receptor (suramin 100 microm), the dinucleotide receptor [diinosine pentaphosphate 30 microm (IP5I)] or adenosine receptors [8-(P-sulfophenyl) theophylline 50 microm (8-SPT)]. Results are %-change (mean +/- SEM) from value before exposure. AP5A increased contractile force by 22 +/- 3%* (*P <0.05), and IP5I abolished this. AP5A prolonged APD90 by 7 +/- 2%*. AP5A significantly reduced response to isoproterenol acutely from 31 +/- 4* (controls) to 9 +/- 4% and after 45 min washout from 61 +/- 14* (controls) to 16 +/- 5%. 8-SPT abolished the sustained effect. Increase in contractile force by AP5A was confirmed in human atria trabecula preparations. AP5A increased contractile force and prolonged APD90. Contractile force increased by stimulation of the dinucleotide receptor in guinea pig myocardium. The sustained anti-beta-adrenergic effect of AP5A was due to adenosine receptor stimulation.


Cloning of genes involved in chromosomal translocations by high-resolution single nucleotide polymorphism genomic microarray.
High-resolution single nucleotide polymorphism genomic microarray (SNP-chip) is a useful tool to define gene dosage levels over the whole genome, allowing precise detection of deletions and duplications/amplifications of chromosomes in cancer cells. We found that this new technology can also identify breakpoints of chromosomes involved in unbalanced translocations, leading to identification of fusion genes. Using this technique, we found that the PAX5 gene was rearranged to a variety of partner genes including ETV6, FOXP1, AUTS2, and C20orf112 in pediatric acute lymphoblastic leukemia (ALL). The 3' end of the PAX5 gene was replaced by the partner gene. The PAX5 fusion products bound to PAX5 recognition sequences as strongly as wild-type PAX5 and suppressed its transcriptional activity in a dominant-negative fashion. In human B cell leukemia cells, binding of wild-type PAX5 to a regulatory region of BLK, one of the direct downstream target genes of PAX5, was diminished by expression of the PAX5-fusion protein, leading to repression of BLK. Expression of PAX5-fusion genes in murine bone marrow cells blocked development of mature B cells. PAX5-fusion proteins may contribute to leukemogenesis by blocking differentiation of hematopoietic cells into mature B cells. SNP-chip is a powerful tool to identify fusion genes in human cancers.


Activating both Halogen and Chalcogen Bonding Interactions in Cation Radical Salts of Iodinated Tetrathiafulavalene Derivatives.
Halogen bonding (XB) interactions are investigated in cation radical salts of bis(methylthio)-5,5'-diiodotetrathiafulvalene (1). Electrocrystallization of 1 in the presence of Bu4 NCl affords a 1 : 1 salt formulated as (E-1)Cl. Particularly strong I⋅⋅⋅Cl- XB interactions are observed around the Cl- anion with the distances at 78 % the sum of the van der Waals radii, a consequence of the XB charge activation in the cation radical. Moreover, the Cl- environment is complemented by two extra S⋅⋅⋅Cl- chalcogen bonding (ChB) interactions, an original feature among reported halide salts of TTF derivatives. Electrostatic potential calculations on the cation radical further demonstrate the efficient activation of the S atoms of the 1,3-dithiole rings (Vs,max =87.2 kcal/mol), as strong as with the iodine atoms (Vs,max =87.9 kcal/mol). The radical cations form weakly dimerized stacks, as confirmed by the variable-temperature magnetic susceptibility and the weak conductivity (4.8×10-5 S cm-1 ).


Efficacy and safety of quinine-artesunate in an HIV-positive patient with severe falciparum malaria.
Severe falciparum malaria is a medical emergency that is associated with a high rate of mortality, even when treated in an Intensive Care Unit. Until recently, intravenous quinine was the standard treatment; however, artemisin derivatives are now regarded as the first-line treatment for multidrug-resistant falciparum malaria. Although several studies have demonstrated the superiority of Artesunate, this drug is not licensed in many countries. This article describes the case of an HIV-positive patient, who returned from Africa and presented with 10% parasitemia and clinical signs of severe falciparum malaria; this individual was successfully treated with a combination of artesunate and quinine. Artesunate was imported from the foreign market, and written consent for its administration was obtained in advance. Parasite clearance was rapidly achieved; however, on day IV, the patient developed acute respiratory distress syndrome that required mechanical ventilation. The patient was extubated on day XIV and discharged on day XXV. Due to its rapid action, artesunate was likely responsible for the good clinical outcome in this case; however, in order to clarify the role of this new combination therapy, further studies are required.


Microevolution in prehistoric Andean populations: chronologic mtDNA variation in the desert valleys of northern Chile.
Archeological evidence suggests that the iconographic and technological developments that took place in the highlands around Lake Titicaca in the Central Andean region had an influence on the cultural elaborations of the human groups in the valleys and the Pacific coast of northern Chile. In a previous communication, we were able to show, by means of a distance analysis, that a craniofacial differentiation accompanied the process of cultural evolution in the valleys (Rothhammer and Santoro [2001] Lat. Am. Antiq. 12:59-66). Recently, numerous South Amerindian mtDNA studies were published, and more accurate molecular techniques to study ancient mtDNA are available. In view of these recent developments, we decided 1) to study chronological changes of ancient mtDNA haplogroup frequencies in the nearby Lluta, Azapa, and Camarones Valleys, 2) to identify microevolutionary forces responsible for such changes, and 3) to compare ancient mtDNA haplogroup frequencies with previous data in order to validate craniometrical results and to reconstruct the biological history of the prehistoric valley groups in the context of their interaction with culturally more developed highland populations. From a total of 97 samples from 83 individuals, 68 samples (61 individuals) yielded amplifications for the fragments that harbor classical mtDNA markers. The haplogroup distribution among the total sample was as follows: 26.2%, haplogroup A; 34.4%, haplogroup B; 14.8%, haplogroup C; 3.3%, haplogroup D; and 21.3%, other haplogroups. Haplogroup B tended to increase, and haplogroup A to decrease during a 3,900-year time interval. The sequence data are congruent with the haplogroup analysis. In fact, the sequencing of hypervariable region I of 30 prehistoric individuals revealed 43 polymorphic sites. Sequence alignment and subsequent phylogenetic tree construction showed two major clusters associated with the most common restriction haplogroups. Individuals belonging to haplogroups C and D tended to cluster together with nonclassical lineages.


On the nature of dense CO adlayers on fcc(100) surfaces: a kinetic Monte Carlo study.
We present a kinetic Monte Carlo lattice gas model including top and bridge sites on a square lattice, with pairwise lateral interactions between the adsorbates. In addition to the pairwise lateral interactions we include an additional interaction: an adsorbate is forbidden to adsorb on a bridge site formed by two surface atoms when both surface atoms are already forming a bond with an adsorbate. This model is used to reproduce the low and high coverage adsorption behaviour of CO on Pt(100) and Rh(100). The parameter set used to simulate CO on Pt(100) produces the c(2 x 2)-2t ordered structure at 0.50 ML coverage, a one-dimensionally ordered structure similar to the experimentally observed (3 square root(2) x square root(2)) - 2t + 2b structure at 0.67 ML coverage, the c(4 x 2)-4t + 2b ordered structure at 0.75 ML coverage, and the recently reported c(6 x 2)-6t + 4b ordered structure at 0.83 ML coverage. The (5 square root(2) x square root(2)) ordered structure at 0.60 ML coverage is not reproduced by our model. The parameter set used to simulate CO on Rh(100) produces the c(2 x 2)-2t ordered structure at 0.50 ML coverage, a one-dimensionally ordered structure similar to the experimentally observed (4 square root(2) x square root(2)) - 2t + 4b structure at 0.75 ML coverage, and the c(6 x 2)-6t + 4b ordered structure at 0.83 ML coverage. Additionally, the simulated change of top and bridge site occupation as a function of coverage matches the trend in experimental vibrational peak intensities.


Large Cell Neuroendocrine Carcinoma of the Lung: A Case Series of 14 Cases.
Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a rare subtype of neuroendocrine tumor, presenting with very aggressive behavior and a poor prognosis. The diagnosis is difficult and requires histological confirmation of the neuroendocrine nature by an immunohistochemical study on a biopsy sample. We retrospectively studied a series of 14 patients from the pneumology department of the Mohammed VI University Hospital of Oujda, Morocco, over a period of five years (from April 2017 to March 2021). The average age was 63.41 years (45-80 years). All our patients were male and smokers. The clinical signs were dominated by deterioration in general condition and dyspnea. Bronchoscopy was performed in 92% of patients, with neoplastic stenosis being the main found aspect, in 35% of cases. The histological diagnosis was obtained by bronchoscopy in 50% of cases. In the remaining cases, it was carried by CT-guided transparietal biopsy in 28% of cases, pleural biopsy in 7% of cases, biopsy of a metastatic site in 7% of cases and finally thoracoscopy with pleural biopsy in the remaining 7% of cases. Therapeutically, no patient received surgical treatment and three patients were put on palliative treatment. The positive diagnosis is often late, which makes the prognosis bad and the therapeutic possibilities limited. Hence the importance of strategies for the prevention of tobacco control and early detection in population at risk.


Clinical effect of postoperative chemoradiotherapy in resected advanced laryngeal squamous cell carcinoma.
Laryngeal squamous cell carcinoma (LSCC) is one of the most prevalent types of head and neck malignancies. Advanced LSCC has failed to demonstrate a satisfactory prognosis, despite the progresses in the diagnosis and treatment, and the optimal treatment modality continues to be debated. To evaluate the clinical utility and survival outcomes of adjuvant chemoradiotherapy (CRT) for patients with resected advanced LSCC, a retrospective analysis of 232 patients with LSCC who had undergone total laryngectomy and neck dissection between 2005 and 2010 was conducted. Of the 232 eligible patients, 167 patients (72%) received surgery alone, whereas 65 patients (28%) received surgery + adjuvant CRT. In the overall cohort, the 5- and 10-year overall survival (OS) rates were 55.2 and 48.3%, respectively. Multivariate analysis revealed that the clinical stage was significantly associated with OS. However, the N classification was an independent indicator in disease-free survival and laryngeal cancer-specific survival. In those patients with stage IV disease, patients receiving adjuvant CRT exhibited a markedly improved survival benefit compared with patients receiving surgical treatment only, following propensity score matching of the data (P<0.05). The application of adjuvant CRT confers additional survival benefits in comparison with surgery-only treatment regimens for advanced LSCC. However, additional prospective studies are required.


Biochemical properties and cellular localization of the Drosophila DG1 cGMP-dependent protein kinase.
The protein encoded by the Drosophila cGMP-dependent protein kinase gene, DG1, was expressed in Sf9 cells. cGMP (10 microM) stimulated histone H2B phosphorylation by the DG1 protein kinase 20-fold. Maximal activity was observed at 40-50 mM Mg2+. The concentrations of cGMP, cAMP, cIMP, 8-bromo-cGMP, and 8-bromo-cAMP that gave 50% activation were 0.19 +/- 0.06, 11.7 +/- 2.8, 5.3 +/- 1.5, 0.04 +/- 0. 01, and 0.62 +/- 0.06 microM, respectively. cGMP activation was cooperative with a Hill coefficient (nH) of 1.28 +/- 0.10, whereas activation by cAMP was not cooperative. DG1 kinase expressed in Sf9 cells was found to be a dimer with an amino-terminal dimerization domain. It also autophosphorylated in a reaction stimulated by cGMP and cAMP. Immunoadsorbed DG1 protein from fly extracts was also capable of autophosphorylation, and this assay was used to quantitate the DG1 kinase in extracts from heads and bodies of adults and whole embryos. Activity was highest in heads of either sex and male bodies, intermediate in female bodies, and lowest in embryos. These results were in accord with DG1 mRNA abundance. Tissue distribution of the DG1 kinase was investigated by immunohistochemistry. In embryos, specific immunoreactivity was observed in large cells scattered along the anterior-posterior axis at stage 13. Prominent staining of adult heads was restricted to the proximal level of the lamina cortex.


Obstetrical and neonatal outcomes of pregnancies following gastric bypass surgery: a retrospective cohort study in a French referral centre.
The objective of this study was to analyze obstetrical and neonatal outcomes following Roux en Y Gastric Bypass procedures (RYGBP). A retrospective cohort study was conducted in a single French tertiary perinatal care and bariatric center. The study involved 24 pregnancies, following RYGBP (exposed group) and two different control groups (non-exposed groups). A body mass index (BMI)-matched control group included 120 pregnancies matched for age, parity, and pregnancy BMI. A normal BMI control group included 120 pregnancies with normal BMI (18.5-24.9 kg/m(2)), matched for age and parity. Hospital data were reviewed from all groups in the same 6-year period. Obstetrical and neonatal outcomes after RYGB were compared, separately, to the two different-matched control groups. The median interval from RYGBP to conception was 26.6 (range: 3-74) months. Rates of perinatal complications did not differ significantly between the RYGBP group and normal BMI and BMI-matched controls groups. The rate of Cesarean section before labor was higher in the RYGBP patients than in the normal BMI control group (25% vs. 9.3% respectively, p = 0.04). Weight gain was lower in the RYGBP patients than normal BMI control group (5.8 kg vs. 13.2 kg respectively, p < 0.0001). Birthweight was also lower in the RYGBP group than those in normal BMI and BMI-matched controls groups (2,948.2 g vs. 3,368.2 g and 3,441.8 g, respectively, p < 0.0001). RYGBP surgery was associated with reduced birthweight, suggesting a possible role of nutritional growth restriction in pregnancy.


Finally "deliberate by design": milestones in the delivery of health care for U.S. military family members.
The development of medical care for U.S. military families and retirees was serendipitous, a fortunate accident. The formal development of military family medical care required the evolution of three factors: the emergence of a standing army, frontiers to guard, and a peace to defend. These factors were first realized in the late 19th Century, and beginning at that point in U.S. history, seven key years highlight major milestones in the history of military family member medical care. At the same time, these years exemplify changing ideas of disease and of health care and how the physical design of clinics and hospitals reflects and impacts these ideas. The Fort Belvoir Community Hospital, which opens in 2011, exemplifies the Nation's best example of green hospital construction, patient and family centered care, and evidence-based design in a Culture of Excellence that demonstrates that military family medical care is finally "deliberate by design."


Enlargement of thalamic nuclei in Tourette syndrome.
The basal ganglia and thalamus together connect in parallel closed-loop circuits with the cortex. Previous imaging studies have shown modifications of the basal ganglia and cortical targets in individuals with Tourette syndrome (TS), but less is known regarding the role of the thalamus in TS pathogenesis. To study the morphological features of the thalamus in children and adults with TS. A cross-sectional, case-control study using anatomical magnetic resonance imaging. University research center. The 283 participants included 149 with TS and 134 normal control individuals aged 6 to 63 years. Conventional volumes and measures of surface morphology of the thalamus. Analyses of conventional volumes and surface morphology were consistent in demonstrating an enlargement in TS-affected thalami. Overall volumes were 5% larger in the group composed of children and adults with TS. Statistical maps of surface contour demonstrated enlargement over the lateral thalamus. Post hoc testing indicated that differences in IQ, comorbid illnesses, and medication use did not account for these findings. Morphological abnormalities in the thalamus, together with the disturbances reported in the sensorimotor cortex, striatum, and globus pallidus, support the hypothesis of a circuitwide disorder within motor pathways in TS. The connectivity and function of the numerous and diverse thalamic nuclei within cortical-subcortical circuits constitute an anatomical crossroad wherein enlargement of motor nuclei may represent activity-dependent hypertrophy within this component of cortical-subcortical motor circuits, or an adaptive response within a larger putative compensatory system that could thereby directly modulate activity in motor circuits to attenuate the severity of tics.


Mechanisms of Nucleation and Solid-Solid-Phase Transitions in Triblock Janus Assemblies.
A model, including the chemical details of core nanoparticles as well as explicit surface charges and hydrophobic patches, of triblock Janus particles is employed to simulate nucleation and solid-solid phase transitions in two-dimensional layers. An explicit solvent and a substrate are included in the model, and hydrodynamic and many-body interactions were taken into account within many-body dissipative particle dynamics simulation. In order not to impose a mechanism a priori, we performed free (unbiased) simulations, leaving the system the freedom to choose its own pathways. In agreement with the experiment and previous biased simulations, a two-step mechanism for the nucleation of a kagome lattice from solution was detected. However, a distinct feature of the present unbiased versus biased simulations is that multiple nuclei emerge from the solution; upon their growth, the aligned and misaligned facets at the grain boundaries are introduced into the system. The liquid-like particles trapped between the neighboring nuclei connect them together. A mismatch in the symmetry planes of neighboring nuclei hinders the growth of less stable (smaller) nuclei. Unification of such nuclei at the grain boundaries of misaligned facets obeys a two-step mechanism: melting of the smaller nuclei, followed by subsequent nucleation of liquid-like particles at the interface of bigger neighboring nuclei. Besides, multiple postcritical nuclei are formed in the simulation box; the growth of some of which stops due to introduction of a strain in the system. Such an incomplete nucleation/growth mechanism is in complete agreement with the recent experiments. The solid-solid (hexagonal-to-kagome) phase transition, at weak superheatings, obeys a two-step mechanism: a slower step (formation of a liquid droplet), followed by a faster step (nucleation of kagome from the liquid droplet).


Ring-slippage and multielectron redox properties of Fe/Ru/Os-bis(arene) complexes: does hapticity change really cause potential inversion?
Bis(hexamethylbenzene) complexes of the group 8 metals (Fe, Ru, Os) show surprising diversity in their electron-transfer mechanisms and associated thermodynamics for the M(II) → M(I) → M(0) redox series. In electrochemical experiments, the Fe complex exhibits normally ordered potentials separated by ∼1 V, the Ru system shows nearly overlapping one-electron redox events, and Os demonstrates a one-step, two-electron transfer with a peak potential separation suggestive of highly inverted potentials. It has been conjectured that the sequential one-electron transfers observed for Fe are due to the lack of an accessible η(4):η(6) Fe(0) state, destabilizing the fully reduced species. Using an established model chemistry based on DFT, we demonstrate that the hapticity change is a consequence of the bonding throughout this transition metal triad and that apparent multielectron behavior is controlled by the vertical electron attachment component of the M(II) → M(I) redox event. Furthermore, the η(6):η(6) Fe(0) triplet state is more favorable than the hypothetical η(4):η(6) singlet state, emphasizing that the hapticity change is not sufficient for multielectron behavior. Despite both displaying two-electron redox responses, Ru and Os traverse fundamentally different mechanisms based on whether the first (Os) or second (Ru) electron transfer induces the hapticity change. While the electronic structure analysis is limited to the Fe triad here, the conceptual model that we developed provides a general understanding of the redox behavior exhibited by d(6) bis(arene) compounds.


Functional properties, nutritional value, and industrial applications of Niger Oilseeds (Guizotia abyssinica Cass.).
Non-conventional seeds are being considered as novel food because their constituents have unique chemical properties and may augment the supply of nutritional and functional products. Niger (Guizotia abyssinica Cass.) seed and its crude oil have been widely used in traditional nutritional and medicinal applications. Consequently, niger seed has been extensively studied for its nutritional value, biological activities, and antioxidative properties. In consideration of their potential utilization, detailed knowledge on the composition of niger oilseeds is of major importance. The diversity of applications to which niger seed can be put gives this oilseed great industrial importance. This review summarizes the nutritional value, functional properties, and industrical applications of niger seeds.


The Physiology, Pathology, and Therapeutic Interventions for ROCK Isoforms in Diabetic Kidney Disease.
Rho-associated coiled-coil-containing protein kinase (ROCK) is a serine/threonine kinase that was originally identified as RhoA interacting protein. A diverse array of cellular functions, including migration, proliferation, and phenotypic modulation, are orchestrated by ROCK through a mechanism involving cytoskeletal rearrangement. Mammalian cells express two ROCK isoforms: ROCK1 (Rho-kinase β/ROKβ) and ROCK2 (Rho-kinase α/ROKα). While both isoforms have structural similarities and are widely expressed across multiple tissues, investigations in gene knockout animals and cell-based studies have revealed distinct functions of ROCK1 and ROCK2. With respect to the kidney, inhibiting ROCK activity has proven effective for the preventing diabetic kidney disease (DKD) in both type 1 and type 2 diabetic rodent models. However, despite significant progress in the understanding of the renal ROCK biology over the past decade, the pathogenic roles of the ROCK isoforms is only beginning to be elucidated. Recent studies have demonstrated the involvement of renal ROCK1 in mitochondrial dynamics and cellular transdifferentiation, whereas ROCK2 activation leads to inflammation, fibrosis, and cell death in the diabetic kidney. This review provides a conceptual framework for dissecting the molecular underpinnings of ROCK-driven renal injury, focusing on the differences between ROCK1 and ROCK2.


GPs understanding of how depression affects gay and HIV positive men.
This article explores qualitative descriptions of how a group of Australian general practitioners understand the relationship between depression, gender, and sexuality in their gay male patients, including gay men who are HIV negative and those who are HIV positive. Thematic analysis of 16 semistructured qualitative interviews with GPs who prescribe s100 HIV medications in Sydney, Adelaide and a rural coastal town in New South Wales, Australia. Recurrent themes regarding how depression affects the gay men these GPs see in their practices in comparison with heterosexual men included: differences in seeking help and accepting treatment; and similarities in emotional expression, overuse of alcohol and recreational drugs, and excessive time spent on work. Issues that complicated the management of depression in these populations included aging, sexual dysfunction, social isolation, loss of family and friendship networks, and poverty. General practitioners with less experience in treating gay and HIV positive men can benefit from these insights to ensure that depression is accurately detected and effectively treated.


Targeting, internalization, and cytotoxicity of methotrexate-monoclonal anti-stage-specific embryonic antigen-1 antibody conjugates in cultured F-9 teratocarcinoma cells.
Methotrexate (MTX) conjugates of a monoclonal antibody, anti-SSEA-1, containing an average of 45 mol MTX/mol of immunoglobulin M, were prepared by a carbodiimide coupling reaction. Binding experiments indicate that conjugation does not decrease the affinity of the antibody for its antigen. The conjugate strongly inhibits the growth of SSEA-1-bearing F-9 teratocarcinoma cells, with 50% inhibitory dose of 4.5 nM MTX, which makes it more active than free MTX (50% inhibitory dose of 15 nM). The drug-free antibody is not cytotoxic to F-9 cells at the concentrations used. The high efficacy of the conjugated drug may be due in part to the fact that anti-SSEA-1 antibody is an immunoglobulin M. MTX conjugated to nonspecific immunoglobulin M has little inhibitory effect (50% inhibitory dose of 150 nM). When acting on SSEA-1 negative cells, the two conjugates have only a small but identical effect. Thiamine pyrophosphate, an inhibitor of MTX transport, can prevent the cytotoxicity of the free MTX but not that of the anti-SSEA-1 conjugate. Leupeptin, an inhibitor of lysosomal protease, can partially protect F-9 cells against the antibody conjugate but not against free MTX. These results indicate that the MTX antibody conjugate binds specifically to F-9 cells, and is internalized and intracellularly degraded to release a small molecular active drug. Pretreatments of F-9 cells for 1 h with unlabeled antibody inhibits the subsequent uptake of identical concentration of labeled conjugate. The rate of internalization, however, regains almost normal values within 4 h, indicating a rapid reappearance of free antigenic sites at the cell surface.


Economic evaluation of docetaxel-gemcitabine versus vinorelbine-cisplatin combination as front-line treatment of patients with advanced/metastatic non-small-cell lung cancer in Greece: a cost-minimization analysis.
An economic evaluation was undertaken, alongside a randomized phase III study, to assess docetaxel-gemcitabine (DG) relative to vinorelbine-cisplatin (VC) combination as front-line treatment of patients with advanced/metastatic non-small-cell lung cancer. No differences were found in efficacy, thus a cost-minimization analysis was carried out. Treatment cost accounts for the administration of first- and second-line chemotherapy, for concomitant medications, for laboratory and biochemical examinations, and for hospitalizations due to adverse events. Unit prices used reflect 2008 and are common among National Health Service hospitals in Greece. The mean total cost of therapy in the DG group [14045 euros, 95% uncertainty interval (UI) 12628 euros-15390 euros], was significantly higher than in the VC group (8143 euros, 95% UI 7314 euros-9067 euros). Even though the combination VC has similar effectiveness compared with DG in patients with metastatic lung cancer, it is associated with a lower overall treatment cost and hence, it is preferable from an economic perspective. However, it should be noted that although VC is associated with lower cost, it is also more toxic than DG regimen, a significant parameter that should be considered in clinical decisions.


Scene construction in schizophrenia.
Recent research has revealed that schizophrenia patients are impaired in remembering the past and imagining the future. In this study, we examined patients' ability to engage in scene construction (i.e., the process of mentally generating and maintaining a complex and coherent scene), which is a key part of retrieving past experiences and episodic future thinking. 24 participants with schizophrenia and 25 healthy controls were asked to imagine new fictitious experiences and described their mental representations of the scenes in as much detail as possible. Descriptions were scored according to various dimensions (e.g., sensory details, spatial reference), and participants also provided ratings of their subjective experience when imagining the scenes (e.g., their sense of presence, the perceived similarity of imagined events to past experiences). Imagined scenes contained less phenomenological details (d = 1.11) and were more fragmented (d = 2.81) in schizophrenia patients compared to controls. Furthermore, positive symptoms were positively correlated to the sense of presence (r = .43) and the perceived similarity of imagined events to past episodes (r = .47), whereas negative symptoms were negatively related to the overall richness of the imagined scenes (r = -.43). The results suggest that schizophrenic patients' impairments in remembering the past and imagining the future are, at least in part, due to deficits in the process of scene construction. The relationships between the characteristics of imagined scenes and positive and negative symptoms could be related to reality monitoring deficits and difficulties in strategic retrieval processes, respectively.


Anti-HLA-A, -B, -DR, -DQB1 and -DQA1 antibodies reactive epitope determination with HLAMatchmaker in multipare awaiting list for heart transplant.
Human leukocyte antigen (HLA) antibodies represent a significant risk factor for transplant failure. It is very important to characterize anti-HLA antibodies as epitopes rather than antigens so that this knowledge can be applied clinically. The aim of the study was to investigate the extra reactivity patterns in sensitized multipare. Here, we have used the HLAMatchmaker program, a theoretical algorithm, to explain these unexpected antibody reactivity patterns in multipare awaiting for heart transplant. The patient was sensitized during pregnancy by alleles HLA-A(*)24:02, HLA-DRB1(*)07:01, HLA-DRB4(*)01:01, DQB1(*)02:02 and DQA1(*)02:01 mismatches with development of respective antibodies. However, the patient' sera were shown an unexpected reactivity not directed toward HLA mismatches of daughters: A(∗)23:01, A(*)24:03 and B(*)15:12 for class I and DRB4(*)01:03, DRB1(*)09:02, DRB1(*)09:01, DQB1(*)03:01, DQB1(*)03:03, DQB1(*)03:02, DQB1(*)04:02, DQB1(*)04:01 and DQB1(*)02:01 for class II. By HLAMatchmaker analysis we found that these antibodies reacted with eplet shared by antigens in single allele Luminex panels. These eplets were: 62EE, 66GKH, 70KAH, 71HS, 127K, 113YH, 144KR, 150AAH, 151AHV, 163TG and 167DG for class I and 4Q, 74RRAE, 71RRA, 98KN, 120N, and 135G, 25FT, 34HE, 41ER, 47EK2, 48LF for class II. Thus, HLAMatchmaker software together with to solid phase techniques could open new horizons for a more precise characterization of the HLA-antibodies.


Light-induced carotenogenesis in Myxococcus xanthus: light-dependent membrane sequestration of ECF sigma factor CarQ by anti-sigma factor CarR.
Light-induced carotenogenesis in Myxococcus xanthus is under the control of the carQRS operon. CarQ, a proposed extracytoplasmic (ECF) RNA polymerase sigma factor, is required for expression of the operon and the carC gene that encodes phytoene dehydrogenase. CarR, an inner membrane protein in Escherichia coli, is essential for carQRS promoter inactivation in the dark. CarS is required for the light-dependent expression of the promoter of the carB gene cluster that encodes the rest of the structural genes for carotenogenesis. Regulation of carQRS is dependent on the stoichiometry of CarQ and CarR. Increasing the copy number of carQ over carR led to constitutive carotenogenesis, as did loss of translational coupling between carQ and carR. The severity of the constitutive phenotype depended on the distance between the uncoupled genes. When expressed in M. xanthus, a CarR:beta-galactosidase fusion protein disappeared in the light. We propose that anti-sigma factor CarR sequesters CarQ to the membrane in the dark, but, in the light, loss of CarR leads to release of the sigma factor.


Investigation of the Structure-Property Effect of Phosphorus-Containing Polysulfone on Decomposition and Flame Retardant Epoxy Resin Composites.
The flame retardant modification of epoxy (EP) is of great signification for aerospace, automotive, marine, and energy industries. In this study, a series of EP composites containing different variations of phosphorus-containing polysulfone (with a phosphorus content of approximately 1.25 wt %) were obtained. The obtained EP/polysulfone composites had a high glass transition temperature (Tg) and high flame retardancy. The influence of phosphorus-containing compounds (ArPN₂, ArPO₂, ArOPN₂ and ArOPO₂) on the thermal properties and flame retardancy of EP/polysulfone composites was investigated by thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), a UL-94 vertical burning test, and cone calorimeter tests. The phosphorus-containing polysulfone enhanced the thermal stability of EP. The more stable porous char layer, less flammable gases, and a lower apparent activation energy at a high degree of conversion demonstrated the high gas inhibition effect of phosphorus-containing compounds. Moreover, the gas inhibition effect of polysulfone with a P⁻C bond was more efficient than the polysulfone with a P⁻O⁻C bond. The potential for optimizing flame retardancy while maintaining a high Tg is highlighted in this study. The flame-retardant EP/polysulfone composites with high thermal stability broaden the application field of epoxy.


End-to-End Handwritten Paragraph Text Recognition Using a Vertical Attention Network.
Unconstrained handwritten text recognition remains challenging for computer vision systems. Paragraph text recognition is traditionally achieved by two models: the first one for line segmentation and the second one for text line recognition. We propose a unified end-to-end model using hybrid attention to tackle this task. This model is designed to iteratively process a paragraph image line by line. It can be split into three modules. An encoder generates feature maps from the whole paragraph image. Then, an attention module recurrently generates a vertical weighted mask enabling to focus on the current text line features. This way, it performs a kind of implicit line segmentation. For each text line features, a decoder module recognizes the character sequence associated, leading to the recognition of a whole paragraph. We achieve state-of-the-art character error rate at paragraph level on three popular datasets: 1.91% for RIMES, 4.45% for IAM and 3.59% for READ 2016. Our code and trained model weights are available at https://github.com/FactoDeepLearning/VerticalAttentionOCR.


Alternative solutions to the problem of selection bias in an analysis of federal residential drug treatment programs.
In an evaluation of prison-based residential drug treatment programs, the authors use three different regression-based approaches to estimating treatment effects. Two of the approaches, the instrumental variable and the Heckman approach, attempt to minimize selection bias as an explanation for treatment outcomes. Estimates from these approaches are compared with estimates from a regression in which treatment is represented by a dummy variable. The article discusses the advantage of using more than one method to increase confidence in findings when possible selection bias is a concern. Three-year outcome data for 2,315 federal inmates are used in analyses where the authors separately examine criminal recidivism and relapse to drug use for men and women. Statistical tests lead the authors to conclude that treatment reduces criminal recidivism and relapse to drug use. The treatment effect was largest when the inference was based on the Heckman approach, somewhat smaller when based on the instrumental variable approach, and smallest when based on the traditional dummy variable approach. Treatment effects for females were not statistically significant.


Bacillus anthracis-derived edema toxin (ET) counter-regulates movement of neutrophils and macromolecules through the endothelial paracellular pathway.
A common finding amongst patients with inhalational anthrax is a paucity of polymorphonuclear leukocytes (PMNs) in infected tissues in the face of abundant circulating PMNs. A major virulence determinant of anthrax is edema toxin (ET), which is formed by the combination of two proteins produced by the organism, edema factor (EF), which is an adenyl cyclase, and protective antigen (PA). Since cAMP, a product of adenyl cyclase, is known to enhance endothelial barrier integrity, we asked whether ET might decrease extravasation of PMNs into tissues through closure of the paracellular pathway through which PMNs traverse. Pretreatment of human microvascular endothelial cell(EC)s of the lung (HMVEC-L) with ET decreased interleukin (IL)-8-driven transendothelial migration (TEM) of PMNs with a maximal reduction of nearly 60%. This effect required the presence of both EF and PA. Conversely, ET did not diminish PMN chemotaxis in an EC-free system. Pretreatment of subconfluent HMVEC-Ls decreased transendothelial 14 C-albumin flux by ~ 50% compared to medium controls. Coadministration of ET with either tumor necrosis factor-α or bacterial lipopolysaccharide, each at 100 ng/mL, attenuated the increase of transendothelial 14 C-albumin flux caused by either agent alone. The inhibitory effect of ET on TEM paralleled increases in protein kinase A (PKA) activity, but could not be blocked by inhibition of PKA with either H-89 or KT-5720. Finally, we were unable to replicate the ET effect with either forskolin or 3-isobutyl-1-methylxanthine, two agents known to increase cAMP. We conclude that ET decreases IL-8-driven TEM of PMNs across HMVEC-L monolayers independent of cAMP/PKA activity.