Mutation analysis in a family with oculocutaneous albinism manifesting in the same generation of three branches.
To elucidate the molecular basis of oculocutaneous albinism with variable expressivity in a family from The Netherlands in which no consanguinity was reported. Three affected family members were screened for mutations in tyrosinase (TYR) and the pink-eye-dilution gene (P) by using SSCP. The melanocortin receptor gene (MC1R) and amplimers of P showing an aberrant banding pattern in SSCP were analyzed by direct sequencing. All participants underwent ophthalmologic examination including funduscopy, and visually evoked potentials were recorded in two cases. The pedigree had three branches A, B, and C. We identified three mutations in P (V443I, N476S, C793F) that cause a compound heterozygous situation in cases from branch A (N476S/C793F) and B (V443I/C793F), who showed oculocutaneous albinism. Hair and skin color followed the light Nordic complexion that was also present in other affected and unaffected members of this family. Descendants of branches A and B showed light complexion with iris translucency and peripheral fundus hypopigmentation independent from the genotype identified. A single descendant had red hair, carrying a well known compound MC1R mutation combination for red hair color and a single heterozygous P mutation. P mutations underlie oculocutaneous albinism in this family. Two known mutations in MC1R caused red hair color in one family member. No modifier effect of MC1R on P mutations could be deduced from the results of this study.


SenseBack - An Implantable System for Bidirectional Neural Interfacing.
Chronic in-vivo neurophysiology experiments require highly miniaturized, remotely powered multi-channel neural interfaces which are currently lacking in power or flexibility post implantation. To resolve this problem we present the SenseBack system, a post-implantation reprogrammable wireless 32-channel bidirectional neural interfacing device that can enable chronic peripheral electrophysiology experiments in freely behaving small animals. The large number of channels for a peripheral neural interface, coupled with fully implantable hardware and complete software flexibility enable complex in-vivo studies where the system can adapt to evolving study needs as they arise. In complementary \textit{ex-vivo} and \textit{in-vivo} preparations, we demonstrate that this system can record neural signals and perform high-voltage, bipolar stimulation on any channel. In addition, we demonstrate transcutaneous power delivery and Bluetooth 5 data communication with a PC. The SenseBack system is capable of stimulation on any channel with 20 V of compliance and up to 315 A of current, and highly configurable recording with per-channel adjustable gain and filtering with 8 sets of 10-bit ADCs to sample data at 20 kHz for each channel. To our knowledge this is the first such implantable research platform offering this level of performance and flexibility post-implantation (including complete reprogramming even after encapsulation) for small animal electrophysiology. Here we present initial acute trials, demonstrations and progress towards a system that we expect to enable a wide range of electrophysiology experiments in freely behaving animals.


Erroneous continuous cardiac output by calibrated pulse contour analysis.
Pulse contour analysis techniques are used for beat-to-beat tracking of cardiac output in critically ill patients. However, an adequate pulse pressure waveform signal and identification of the appropriate (i.e. systolic) part of the waveform by the monitor are crucial for correct calculation of continuous cardiac output. We observed a case where the monitor failed to correctly identify the systolic part of the waveform during tachycardia thus giving false readings. We would like to emphasize the importance of visually checking the waveform for any irregularities that may cause erroneous calculations before initiating a therapy based on these values. One advantage of the system used here is that the part of the pressure curve used for analysis is automatically indicated.


The influence of topography on male and female fitness components of Atriplex canescens.
The influence of environmental heterogeneity on components of male and female fitness is examined using Atriplex canescens growing on steep slopes and alluvium at the slope base as a model system. Female fitness is estimated as the grams of fruit produced per plant and the grams of fruit per gram leaf tissue. Male fitness is estimated as the grams of stamens produced, the number of pollen grains dispersed to a given distance, and the potential number of grams of fruit sired taking into consideration the number and distribution of mates and competing pollen donors. The influence of increased plant size on male and female fitness components, the cost of reproduction (as measured by biomass, joules and nitrogen) on a gross level and a per offspring basis are also examined. The results indicate that the female function is more limited on the slope than the male function. The efficiency of pollen dispersal (the number of pollen grains per unit donor plant volume dispersed to a given distance) is enhanced by growing on slopes. Males become less efficient at dispersing pollen as they increase in size, while the efficiency of female reproduction (grams of fruit per volume or gram leaf tissue) is unaffected by increasing plant size. The cost to a male of siring a gram of fruit is about the same as the cost to a female of producing the gram of fruit. Implications for the evolution of sexual lability and dioecy are discussed.


Low-Grade Carotid Stenosis: Implications of MR Imaging.
Although treatment guidelines are well established for symptomatic patients with greater than 69% carotid stenosis on catheter angiography, optimal management of lower degrees of stenosis remain unclear. Vessel wall MR imaging of the carotid arteries has proved helpful in the evaluation of plaque burden and vulnerable plaque characteristics, and in stratifying risk in low-grade carotid stenosis. This article discusses the pathophysiology and imaging of atherosclerotic plaques resulting in low-grade carotid stenosis, and the corresponding stroke risk and association with plaque elsewhere in the cardiovascular system.


Effects of erythromycin, trimethoprim and clindamycin on attached microbial communities from an effluent dominated prairie stream.
In this study, differing metrics were utilized to measure effects of erythromycin (ER), trimethoprim (TR) and clindamycin (CL) on the structure and function of attached Wascana Creek, SK microbial communities. All three test antibiotics, especially ER, affected community structure and function of biofilms grown in rotating annular reactors. Biofilm thickness, bacterial biomass, and lectin binding biovolume (exopolymeric substances) were consistently less in ER treated biofilms when compared to the control. As well negative effects on protozoan numbers, and carbon utilization were detected. Finally, PCA analyses of DGGE results indicated that bacterial community diversity in ER exposed biofilms was always different from the control. ER exhibited toxic effects even at lower concentrations. Observations on TR and CL exposed biofilms indicated that bacterial biomass, lectin binding biovolume and carbon utilization were negatively affected as well. In terms of bacterial community diversity, however, CL exposed biofilms tended to group with the control while TR grouped with nutrient additions suggesting both nutritive and toxic effects. This study results represent an important step in understanding antibiotic effects, especially ER, on aquatic microbial communities. And because ER is so ubiquitous in receiving water bodies worldwide, the Wascana study results suggest the possibility of ecosystem disturbance elsewhere. Erythromycin (ER) is ubiquitous in waterbodies receiving sewage effluent. Structure and function of microbial communities from an effluent dominated stream were negatively affected by ER, at realistic concentrations.


Structural organization of the estalpha3(1) gene in a Colombian strain of Culex quinquefasciatus differs from that in Cuba.
In Culex mosquitoes (Diptera: Culicidae), the most common mechanism for resistance to organophosphorus (OP) insecticides involves amplification of one or more esterases. Two esterase loci are often involved, with different allelic forms co-amplified. Estalpha3(1) is co-amplified with estbeta1 in a Colombian (COL) strain of Culex quinquefasciatus Say. These two alleles co-migrate on acrylamide gels, often leading to misscoring of the phenotype as elevation of a single estbeta enzyme. By sequencing COL genomic DNA, we determined the estalpha3(1) gene length is 1623 nucleotides. The open reading frame of estalpha3(1) encodes a 540 amino acid protein, as for estalpha2(1) in strain Pel RR from Sri Lanka. The intron/exon boundaries of estalpha3(1) are identical to those of estalpha2(1), suggesting that they are alleles of the same locus. The COL estalpha3(1) gene differs from estaalpha3(2) in strain MRES from Cuba, although they have equivalent electrophoretic mobility, showing that these two strains contain distinct resistance-associated amplicons. Twenty nucleotide differences were scored between the MRES partial 495 bp sequence and that in the COL strain, with two amino acid changes, demonstrating distinct estalpha enzymes. Our sequencing data show 95% identity between the three estalpha genes (each has six introns and seven exons) in OP-resistant Cx. quinquefasciatus. Amplified estalpha3(1) and estbeta1 are at least 10kb apart in temephos-selected COL and 2.7kb apart in Pel RR, whereas these non-amplified genes are only 1.7kb apart in the nonselected parental COL stock, as in Pel SS (susceptible Sri Lankan strain), demonstrating that this region of the genome is susceptible to expansion and contraction.


Product and product-independent induction of butane oxidation in Pseudomonas butanovora.
Pseudomonas butanovora grows on butane by means of an inducible soluble alkane monooxygenase (sBMO). The induction of sBMO was studied using the wild type and a sBMO reporter strain. The reporter strain has the lacZ::kan cassette inserted into bmoX, the gene that encodes the alpha-subunit of the hydroxylase of sBMO. The beta-galactosidase activity in the reporter strain was not induced by butane, but was induced by 1-butanol and butyraldehyde. P. butanovora expressed sBMO product-independent activity at 3.0+/-1 nmol ethylene oxide min(-1) mg protein(-1) in stationary phase. The sBMO product-independent activity likely primes the expression of sBMO by butane.


Preclinical evaluation of the antiproliferative potential of STI571 in Hodgkin's disease.
STI571 is a selective tyrosine kinase inhibitor with proven therapeutic potential in malignancies expressing c-kit. A strong c-kit and stem cell factor expression was detected in the Hodgkin and Reed Sternberg cell line L1236, but not in 20 primary cases of classical Hodgkin's disease. Proliferation of L1236 cells was neither affected by addition of stem cell factor nor by neutralising anti-stem cell factor antibodies or STI571. Results suggest that patients with Hodgkin's disease may not benefit from therapy with STI571.


Determination of endosulfan and its metabolites in human urine using gas chromatography-tandem mass spectrometry.
A method was developed for determining the occupational exposure to endosulfan and its main metabolites (endosulfanether, -lactone and -sulfate) in human urine using dieldrin as an internal standard. Solid phase extraction (SPE) and gas chromatography-tandem mass spectrometry (GC-MS-MS) have been used due to their high sensitivity and selectivity in avoiding most matrix interferences. The recovery efficiencies of the tested compounds yielded more than 89.2% at the fortification level of 10 ng ml(-1) in urine and their relative standard deviations were between 9.1 and 12.8%. The detection limit of each compound ranged between 6 and 18 pg ml(-1). Urine samples from nine pest control operators were analysed and total endosulfan concentrations between 94 and 2038 pg ml(-1) were found.


Neuroinflammation and galectins: a key relationship in neurodegenerative diseases.
Neurodegeneration is a pathological condition that is associated with the loss of neuronal function and structure. In neurodegenerative diseases, mounting evidence indicates that neuroinflammation is a common factor that contributes to neuronal damage and neurodegeneration. Neuroinflammation is characterized by the activation of microglia, the neuroimmune cells of the central nervous system (CNS), which have been implicated as active contributors to neuronal damage. Glycan structure modification is defining the outcome of neuroinflammation and neuronal regeneration; moreover, the expression of galectins, a group of lectins that specifically recognize β-galactosides, has been proposed as a key factor in neuronal regeneration and modulation of the inflammatory response. Of the different galectins identified, galectin-1 stimulates the secretion of neurotrophic factors in astrocytes and promotes neuronal regeneration, whereas galectin-3 induces the proliferation of microglial cells and modulates cell apoptosis. Galectin-8 emerged as a neuroprotective factor, which, in addition to its immunosuppressive function, could generate a neuroprotective environment in the brain. This review describes the role of galectins in the activation and modulation of astrocytes and microglia and their anti- and proinflammatory functions within the context of neuroinflammation. Furthermore, it discusses the potential use of galectins as a therapeutic target for the inflammatory response and remodeling in damaged tissues in the central nervous system.


Evaluating of veterinarians' and veterinary students' knowledge and clinical use of pulse oximetry.
We hypothesized that veterinarians and veterinary students may lack key knowledge about pulse oximetry, which may result in this type of patient monitor not being used on appropriate patient populations or to its full capabilities. A questionnaire was developed to assess an individual's knowledge and understanding of pulse oximetry. Residents and specialists in anesthesiology and critical care at several academic institutions were surveyed first to assess the questionnaire for clarity and to serve as a control group. General veterinary practitioners (GPs) attending continuing education courses at the University of Georgia were surveyed over a 24-month period. Students entering their senior-year anesthesiology rotation at the University of Georgia were also surveyed. Residents and specialists (69% correct responses) scored significantly higher than senior students (46%), who scored significantly higher than GPs (34%). Only 15% of GPs and 21% of senior students reported that they had received training in pulse oximetry in school. Those who had received training scored significantly higher than those who had not. Many GPs did not report using a pulse oximeter on their critical patients under anesthesia, a group that would be expected to benefit from its use. Veterinarians have a poor understanding of how pulse oximetry works, the information it provides, and how best to apply it to their patients. Furthermore, the respondents did not use pulse oximeters in a manner that would yield the most information and result in the greatest benefit to the patient relative to the cost of the instrument. Didactic training in veterinary curricula and during continuing education opportunities continues to be necessary in order to produce veterinarians who have an understanding of the technologies available to improve patient care.


Astigmatic outcomes in myopic wavefront-guided laser in situ keratomileusis versus wavefront-guided photorefractive keratectomy using vector analysis.
To compare astigmatic outcomes between eyes having wavefront-guided laser in situ keratomileusis (LASIK) and eyes having wavefront-guided photorefractive keratectomy (PRK). Byers Eye Institute, Stanford University School of Medicine, Palo Alto, California, USA. Prospective randomized case series. Patients had refractive surgery, with one eye treated with LASIK and the other treated with PRK. Eyes were randomized according to ocular dominance. Astigmatism vectors were evaluated using the Alpins vector analysis of astigmatism. Thirty-four patients (68 eyes) had vector analysis; the LASIK and PRK groups had similar target-induced astigmatism vectors (P = 0.75), surgically induced astigmatism vectors (P = 0.86), difference vectors (P = 1.0), indices of success (P = 0.4), correction indices (P = 0.28), and flattening indices (P = 0.5). Based on Alpins vector analysis of astigmatism, there were no statistically significant differences between eyes that had LASIK and eyes that had PRK.


Early discrimination of nasopharyngeal carcinoma based on tissue deoxyribose nucleic acid surface-enhanced Raman spectroscopy analysis.
Surface-enhanced Raman spectroscopy (SERS) was employed to detect deoxyribose nucleic acid (DNA) variations associated with the development of nasopharyngeal carcinoma (NPC). Significant SERS spectral differences between the DNA extracted from early NPC, advanced NPC, and normal nasopharyngeal tissue specimens were observed at 678, 729, 788, 1337, 1421, 1506, and 1573??cm?1, which reflects the genetic variations in NPC. Principal component analysis combined with discriminant function analysis for early NPC discrimination yielded a diagnostic accuracy of 86.8%, 92.3%, and 87.9% for early NPC, advanced NPC, and normal nasopharyngeal tissue DNA, respectively. In this exploratory study, we demonstrated the potential of SERS for early detection of NPC based on the DNA molecular study of biopsy tissues.


Management of postoperative bleeding after laparoscopic left colectomy.
Lower gastrointestinal bleeding after left colectomy is an uncommon complication that can lead to critical situation. Diagnostic and therapeutic manoeuvres should be performed in emergency with step-by-step strategy in order to avoid reoperation. This study aims to identify bleeding risks factors and describe a management strategy. This is a retrospective study of patients who underwent left colectomy with primary anastomosis, from May 2004 to December 2013. We studied their demographic characteristics, surgical procedures and postoperative courses, more specifically hemorrhagic complications, management of bleeding and outcomes. Hemorrhagic anastomotic complication occurred in 47 of the 729 (6.4 %) patients after left colectomy. Neither anticoagulant nor antiaggregant treatment was associated with postoperative bleeding. Among the 47 patients with bleeding, endoscopy was performed in 37 (78.7 %). At the time of endoscopy, the bleeding was spontaneously stopped in nine (24.3 %). Therapeutic strategy used clips in 10 (27.0 %) cases, mucosal sclerosis in 11 (29.7 %) and both in 7 (18.9 %) cases. Four (8.5 %) patients required blood transfusion for treatment of this gastrointestinal bleeding. Five (10.6 %) patients with bleeding were reoperated in this group because early endoscopy showed associated anastomotic leakage. Based on a multivariate analysis, stapled anastomosis and diverticular disease were independent factors associated with anastomotic bleeding. Postoperative anastomotic bleeding is not so uncommon after left colectomy. This complication should be particularly dreaded in patients who underwent stapled colorectal anastomosis for diverticular disease. With the use of clip or mucosal sclerosis, early endoscopy is a safe and efficient treatment.


Cochlear implantation in children with congenital unilateral deafness: Mid-term follow-up outcomes.
Although cochlear implantation is widely used to treat unilateral deafness in adults, very little literature exists on its use and effects on the paediatric population. This report adds to the literature showing the mid-term follow-up outcomes achieved by these children. Three children with congenital unilateral deafness were studied after implantation. Speech perception in noise, and sound localization ability were evaluated using age-appropriate materials. The preliminary data of our small group of 3 children with congenital unilateral profound hearing loss revealed that up to 3 years post-implantation, congenitally deaf children who received a cochlear implant after 4 years of age do not demonstrate binaural hearing benefits. Early intervention in the prelingual phase may be crucial for the development of binaural hearing.


Comparative effects of levobupivacaine and racemic bupivacaine on excitotoxic neuronal death in culture and N-methyl-D-aspartate-induced seizures in mice.
We compared the neurotoxic profile of racemic bupivacaine and levobupivacaine in: (i) a mouse model of N-methyl-D-aspartate (NMDA)-induced seizures and (ii) in an in vitro model of excitotoxic cell death. When used at high doses (36 mg/kg) both bupivacaine and levobupivacaine reduced the latency to NMDA-induced seizures and increased seizure severity. However, levobupivacaine-treated animals underwent less severe seizures as compared with bupivacaine-treated animals. Lower doses of levobupivacaine and bupivacaine had opposite effects on NMDA-induced seizures. At doses of 5 mg/kg, levobupivacaine increased the latency to partial seizures and prevented the occurrence of generalized seizures, whereas bupivacaine decreased the latency to partial seizures and did not influence the development of generalized seizures. In in vitro experiments, we exposed primary cultures of mouse cortical cells, containing both neurons and astrocytes, to 100 microM NMDA for 10 min for the induction of excitotoxic neuronal death. This treatment killed 70-80% of the neuronal population, as assessed 24 h after the excitotoxic pulse. In this particular model, both levobupivacaine and bupivacaine were neuroprotective against NMDA toxicity. However, neuroprotection by levobupivacaine was seen at lower concentrations (with respect to bupivacaine) and was maintained at concentrations of 3 mM, which are much higher than the plasma security threshold for the drug in vivo. In contrast, no protection against NMDA toxicity was detected when 3 mM concentrations of bupivacaine were applied to the cultures. Our data show a better neurotoxic profile of levobupivacaine as compared to racemic bupivacaine, and are indicative of a safer profile of levobupivacaine in clinical practice.


Specificity of Penicillin Acylases in Deprotection of N-Benzyloxycarbonyl Derivatives of Amino Acids.
Changes in the structure of the N-acyl group in N-acylated amino acid derivatives significantly affect both the recognition and activity of penicillin acylases on this series of substrates. However, penicillin acylases from both Alcaligenes faecalis and Escherichia coli are capable of removing the N-benzyloxycarbonyl protecting group in amino acid derivatives under mild conditions without the use of toxic reagents. Efficiency in using penicillin acylases in preparative organic synthesis can be improved by utilizing modern rational enzyme design methods.


Patient with liver cirrhosis presenting with necrotizing fasciitis due to Acinetobacter junii: A case report and literature review.
Acinetobacter spp. are known to be a cause of nosocomial infections and to have diverse mechanisms of resistance to antimicrobials. Here, we report the case of a patient who presented to our emergency department with necrotizing fasciitis due to Acinetobacter junii as confirmed by Matrix-Assisted Laser Desorption/Ionization Time-of-Flight mass spectrometry (MALDI-TOF MS). Patients with liver cirrhosis are susceptible to gram-negative infection. Moreover, although Acinetobacter spp. infection is best known to be a cause of combat-related-skin and soft-tissue infections, we propose that medical professionals need to consider the presence of these potentially multi-drug-resistant, gram-negative pathogens when treating patients with liver cirrhosis who present with severe soft-tissue infections. To our knowledge, this is the first case report of severe-skin and soft-tissue infections caused by A. junii.


Self-reported effects of perceived social support on marital quality in balanced translocation patients and their spouses undergoing preimplantation genetic testing in China: actor-partner interdependence model.
This study aimed to analyse the relationship between perceived social support and marital quality in balanced translocation patients and their spouses undergoing a preimplantation genetic testing (PGT) treatment cycle in China. The authors assessed the actor and partner effects of perceived social support on marital quality in patient-spouse dyads using a dyadic analysis approach. In total, 59 couples were assessed using self-report questionnaires for marital quality and perceived social support. There were significant differences in marital quality between patients and their spouses (p=.0025) based on the APIM (actor-partner interdependence model) analyses. The perceived social support of both patients (p=.0076) and spouses (p<.001) had a significant effect on individual marital quality for actor effects. Partner effects showed that patients' perceived social support had a significant effect on spouses' marital quality (p=.0156) and the spouses' perceived social support had a significant effect on patients' marital quality (p=.0084). The findings indicate that the level of perceived social support affected both his/her own marital quality and that of his/her spouse.Impact StatementWhat is already known on this subject? Infertility and reproductive treatments affect both partners, that is, the couple as a unit and have a negative impact on an individual's marital satisfaction and social relationships.What do the results of this study add? There are significant differences in marital quality between balanced translocation patients and their spouses. Perceived social support significantly correlated with marital quality in both the actor and partner effects.What are the implications of these findings for clinical practice and/or further research? Health professionals should provide couple-based interventions involving both patients and spouses throughout the PGT treatment to improve perceived social support, thereby improving their marital quality.


Comparison of shear wave elastography (supersonic) with liver biopsy in a cohort of patients from a medium-income country: an observational study.
shear-wave elastography is a non-invasive diagnostic test that calculates the degree of liver fibrosis by measuring liver elasticity. This technique was recently introduced in Colombia. Thus, cutoff points delineating the change between fibrosis stages (using the Metavir scale) have not been previously defined in our patient population. a retrospective study was performed of patients who had undergone two-dimensional shear-wave elastography (2D-SWE) and liver biopsy (LB) between June 2010 and June 2018 at a private outpatient hepatology center in Bogota, Colombia. We used a training dataset (subjects with time between biopsy and 2D-SWE of ≤ 6 months) to establish diagnostic cutoff values and a test dataset (subjects with time between biopsy and 2D-SWE of > 6 months) to validate our results. a total of 453 subjects (training dataset, n = 153; test dataset, n = 300) were included. In the training dataset, the cutoff points were 7.6, 8.4, 9.5 and 10.9 kPa, and the areas under the curve were 0.75, 0.83, 0.89 and 0.94 for mild fibrosis, significant fibrosis, advanced fibrosis and cirrhosis, respectively. In the test dataset, the areas under the curve were 0.77, 0.78, 0.83 and 0.89 for mild fibrosis, significant fibrosis, advanced fibrosis, and cirrhosis, respectively. two-dimensional shear-wave elastography was reliable and useful for the non-invasive evaluation of liver fibrosis, particularly in patients with advanced fibrosis and cirrhosis. Cutoff points for fibrosis in a Hispanic population were described.


Elucidating the Dynamic Nature of Fuel Cell Electrodes as a Function of Conditioning: An ex Situ Material Characterization and in Situ Electrochemical Diagnostic Study.
To increase the commercialization of fuel cell electric vehicles, it is imperative to improve the activity and performance of electrocatalysts through combined efforts focused on material characterization and device-level integration. Obtaining fundamental insights into the ongoing structural and compositional changes of electrocatalysts is crucial for not only transitioning an electrode from its as-prepared to functional state, also known as "conditioning", but also for establishing intrinsic electrochemical performances. Here, we investigated several oxygen reduction reaction (ORR) electrocatalysts via in situ and ex situ characterization techniques to provide fundamental insights into the interfacial phenomena that enable peak ORR mass activity and high current density performance. A mechanistic understanding of a fuel cell conditioning procedure is described, which encompasses voltage cycling and subsequent voltage recovery (VR) steps at low potential. In particular, ex situ membrane electrode assembly characterization using transmission electron microscopy and ultra-small angle X-ray scattering were performed to determine changes in carbon and Pt particle size and morphology, while in situ electrochemical diagnostics were performed either during or after specific points in the testing protocol to determine the electrochemical and interfacial changes occurring on the catalyst surface responsible for oxygen transport resistances through ionomer films. The results demonstrate that the voltage cycling (break-in) step aids in the removal of sulfate and fluoride and concomitantly reduces non-Fickian oxygen transport resistances, especially for catalysts where Pt is located within the pores of the carbon support. Subsequent low voltage holds at low temperature and oversaturated conditions, i.e., VR cycles, serve to improve mass activities by a factor of two to three, through a combined removal of contaminants, surface-blocking species (e.g., oxides), and rearrangement of the catalyst atomic structure (e.g., Pt-Pt and Pt-Co coordination).


Prevalence of hepatitis C virus antibody in a liver transplantation population.
The development of a serologic assay to detect antibodies directed at an antigen (C-100-3) of the hepatitis C virus (anti-HCV) has been a major breakthrough in the long search for causative agents of non-A, non-B (NANB) hepatitis. The frequency of HCV in those who have end-stage liver disease is not known. Moreover, the rate of recurrence after liver transplantation (OLTx) and the rate of acquisition of new HCV infection as a result of the OLTx experience is as yet unknown. This study was performed in an attempt to answer these questions. The prevalence of HCV in 372 patients undergoing OLTx at the University of Pittsburgh was determined. Those transplanted for HBV-related liver disease with hepatoma had the highest rate of HCV antibody positivity (45.4%) followed by those with metabolic liver disease (42.5%), putative NANB liver disease (41.4%), and cryptogenic cirrhosis (20.9%); those with cholestatic liver disease exhibited the lowest rate (16.2%). HCV antibody was positive in only 26.3% of patients with hepatoma. Of those patients who were negative prior to transplantation, 12.2% acquired HCV antibody post-OLTx. In the putative NANB group, no difference was detected in the AST and ALT prior to transplantation in either the HCV antibody-positive or -negative patients. In patients with cryptogenic cirrhosis, those who were positive for HCV antibody had higher transaminase levels prior to transplantation than did those patients who were HCV antibody negative.


Job satisfaction in an oncology nursing team.
to identify the level of attributed, perceived and real job satisfaction of oncology nursing professionals and analyze the relationships between the levels of satisfaction among these workers. a descriptive, quantitative cross-sectional study was conducted using the Index of Work Satisfaction (IWS) to evaluate the nursing team, nurses and technicians/auxiliaries. A total of 348 workers answered the questionnaire, of which 216 were fully completed and considered for the IWS calculation. Autonomy was considered the most important item in attributed satisfaction for the nursing team and nurses. Salary was valorized most by the technicians/auxiliaries. For perceived satisfaction, Professional Status was the most important for all workers. Regarding real satisfaction, Interaction was the most important for the nursing team and technicians/auxiliaries; while the nurses valorized Autonomy. The nurses presented the greatest job satisfaction. a discrepancy was observed in job satisfaction among the oncology nurses, indicating the importance of further quantitative research. identificar o nível de satisfação profissional atribuído, percebido e o real no trabalho de profissionais de enfermagem oncológica e analisar as relações entre os níveis de satisfação desses trabalhadores. estudo quantitativo, descritivo, transversal que utilizou o Índice de Satisfação Profissional (ISP) para avaliar a equipe de enfermagem, enfermeiros e técnicos/auxiliares. Dentre os profissionais, 348 destes responderam o questionário, dos quais 216 foram totalmente preenchidos e considerados para o cálculo do ISP. Autonomia foi mais importante na satisfação atribuída para a equipe de enfermagem e enfermeiros, Remuneração foi mais valorizada pelos técnicos/auxiliares. Para a satisfação percebida, Status profissional foi mais importante para todos os profissionais. Sobre a real satisfação, Interação foi o mais importante para a equipe de enfermagem e técnicos/auxiliares; os enfermeiros valorizaram Autonomia. Os enfermeiros obtiveram maior satisfação profissional. Observou-se discrepância quanto à satisfação profissional dos trabalhadores de enfermagem oncológica, sendo importante maior aprofundamento qualitativo.


Lipopolysaccharide induction of tissue factor in THP-1 cells involves Jun protein phosphorylation and nuclear factor kappaB nuclear translocation.
Tissue Factor (TF) gene expression is transiently induced in human monocytic THP-1 cells by lipopolysaccharide (LPS). We characterized the transcription factor complexes binding to the TF gene promoter LPS response element (LRE) (-220 to -172), which contains binding sites for nuclear factor kappaB (NFkappaB) and activator protein 1 (AP1) transcription factors, and examined the nature of the activation of these factors during a 24-h time course of LPS stimulation. We found proteolysis of the cytoplasmic inhibitory protein IkappaBalpha and nuclear translocation of the NFkappaB/Rel family proteins p65 and c-Rel, corresponding to the transient binding of a p65/c-Rel heterodimer to the kappaB-like site of the LRE. AP1 binding to the LRE was found to be constitutive, with the majority of the AP1 complexes being JunD/Fra-2 heterodimers. A change in the activation state of the AP1 complexes was, however, found to be transient, as determined by JunD phosphorylation of AP1 bound to the proximal binding site. This directly correlates to the transient activation of Jun N-terminal kinase (SAPK/JNK). These data indicate that LPS induction of TF gene expression in monocytic THP-1 cells is regulated by both the transient phosphorylation of Jun-family proteins and the nuclear translocation and transient binding of NFkappaB/Rel proteins.


Influence of nutritional status on plasma levels and relative bioavailability of tetracycline.
Relative bioavailability after oral administration of a single dose and Cmin levels of tetracycline in plasma after multiple doses were determined in groups of well-nourished and under-nourished subjects. The relative bioavailability of tetracycline, assessed by the area under serum concentration time-curves, did not differ in under-nourished and well-nourished patients. The plasma levels were not different in the two groups after the conventional dose of tetracycline HCL 250 mg at 6 hour intervals. However, in these studies under-nourished subjects received a higher dose per kg body weight, which could have compensated for any effect of a shortened half life of the drug. When the dose per kg body weight was reduced, the Cmin levels were lower. On the other hand, with the same dose per kg body weight at more frequent intervals, the plasma concentrations were similar to those in well-nourished subjects. These studies indicate that the dosage regimen should be based both on body weight and on the nutritional status of the individual.


Depressive states amplify both upward and downward counterfactual thinking.
Depression has been linked to counterfactual thinking in many behavioral studies, but the direction of this effect remains disputed. In the current study, the relationship between depression and counterfactual thinking was examined using the event-related potential (ERP) technique. In a binary choice gambling task, outcome feedback of the chosen option and that of the alternative option were both provided, so as to elicit the process of counterfactual comparison. By investigating ERP signals in response to outcome presentation, we discovered that when the fictive outcome was better or worse than the factual outcome, the amplitude of the P3 component was positively correlated with individual levels of depression, but not levels of anxiety. These results indicate that depression strengthens both upward counterfactual thinking and downward counterfactual thinking. The implication of this finding to clinical research is discussed.


Disseminated eruptive giant mollusca contagiosa in an adult psoriasis patient during efalizumab therapy.
Molluscum contagiosum is a common viral skin infection in children with atopic diathesis and not rare in HIV patients. We report a 45-year-old psoriasis patient who developed eruptive mollusca contagiosa during an antipsoriatic treatment with efalizumab.


Treg17 cells are programmed by Stat3 to suppress Th17 responses in systemic lupus.
Systemic lupus erythematosus (SLE) is a complex and potentially fatal autoimmune disorder. Although Th17 cells are thought to be central mediators of SLE, mechanisms underlying their counter regulation remain largely unknown. To help define this, we studied the function of the newly defined Stat3-dependent Th17-specific regulatory T cells (Treg17). Treg-specific deletion of Stat3 was achieved by generating Foxp3(Cre) × Stat3(fl/fl) mice and SLE was induced by intraperitoneal injection of pristane. Lack of Treg17 cells in these mice caused selectively enhanced peritoneal Th17 inflammation. Importantly, Treg17 deficiency also resulted in aggravated pulmonary vasculitis with increased percentages of Th17 cells and significantly higher mortality. Similarly, 4 and 9 months after pristane injection, analysis of renal and systemic immunity showed overshooting Th17 responses in the absence of Treg17 cells, associated with the aggravation of lupus nephritis. Expression of the Th17 characteristic trafficking receptor CCR6 was strikingly reduced on Tregs of Foxp3(Cre) × Stat3(fl/fl) mice, resulting in impaired renal Treg infiltration. Thus, Stat3-induced Treg17 cells are novel antiinflammatory mediators of SLE. One mechanism enabling Treg17 cells to target pathogenic Th17 responses is shared expression of the chemokine receptor CCR6.


Elemental mapping in fossil tooth root section of Ursus arctos by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS).
Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) was used to map the matrix (Ca, P) and trace (Ba, Sr, Zn) elements in the root section of a fossilized brown bear (Ursus arctos) tooth. Multielemental analysis was performed on a (2.5 × 1.5)cm(2) area. For elemental distribution, a UP 213 laser ablation system was coupled either with a quadrupole or a time of flight ICP-MS. The cementum and dentine on the slice of the sample surface were clearly distinguishable, especially changes in elemental distribution in the summer and winter bands in the fossil root dentine. Migration and diet of U. arctos were determined on the basis of fluctuations in Sr/Zn ratio and their contents. Quantification was accomplished with standard reference material of bone meal (NIST 1486) and by the use of electron microprobe analysis (EMPA). Changes in Sr/Zn and Sr/Ba ratios relating to the season, and composition of food during the lifetime of the animal are discussed on basis of analysis of light stable isotopes. It was observed that there was an increase in the Sr/Zn ratio during the winter season caused by a reduction of food intake during hibernation. Above mentioned inferences drawn from elemental data obtained by LA-ICP-MS were confirmed independently by determination of carbon, nitrogen and strontium isotopes. Moreover, diagenesis and its interfering influence on the biogenic composition of cementum and dentine were resolved. According to the distribution and/or content of the element of interest, post-mortem alterations were revealed. Namely, U, Na, Fe, Mg and F predicate about the suitability of the selected area for determination of migration and diet.


Putting on the brakes: Bacterial impediment of wound healing.
The epithelium provides a crucial barrier to infection, and its integrity requires efficient wound healing. Bacterial cells and secretomes from a subset of tested species of bacteria inhibited human and porcine corneal epithelial cell migration in vitro and ex vivo. Secretomes from 95% of Serratia marcescens, 71% of Pseudomonas aeruginosa, 29% of Staphylococcus aureus strains, and other bacterial species inhibited epithelial cell migration. Migration of human foreskin fibroblasts was also inhibited by S. marcescens secretomes indicating that the effect is not cornea specific. Transposon mutagenesis implicated lipopolysaccharide (LPS) core biosynthetic genes as being required to inhibit corneal epithelial cell migration. LPS depletion of S. marcescens secretomes with polymyxin B agarose rendered secretomes unable to inhibit epithelial cell migration. Purified LPS from S. marcescens, but not from Escherichia coli or S. marcescens strains with mutations in the waaG and waaC genes, inhibited epithelial cell migration in vitro and wound healing ex vivo. Together these data suggest that S. marcescens LPS is sufficient for inhibition of epithelial wound healing. This study presents a novel host-pathogen interaction with implications for infections where bacteria impact wound healing and provides evidence that secreted LPS is a key factor in the inhibitory mechanism.


Study of COVID-19 pandemic in London (UK) from urban context.
COVID-19 transmission in London city was discussed in this work from an urban context. The association between COVID-19 cases and climate indicators in London, UK were analysed statistically employing published data from national health services, UK and Time and Date AS based weather data. The climatic indicators included in the study were the daily averages of maximum and minimum temperatures, humidity, and wind speed. Pearson, Kendall, and Spearman rank correlation tests were selected for data analysis. The data was considered up to two different dates to study the climatic effect (10th May in the first study and then updated up to 16th of July in the next study when the rest of the data was available). The results were contradictory in the two studies and it can be concluded that climatic parameters cannot solely determine the changes in the number of cases in the pandemic. Distance from London to four other cities (Birmingham, Leeds, Manchester, and Sheffield) showed that as the distance from the epicentre of the UK (London) increases, the number of COVID-19 cases decrease. What should be the necessary measure to be taken to control the transmission in cities have been discussed.


Preventive effects of ophiopogon-polysaccharide on apiponectin in gestational diabetes mellitus rat.
To investigate the effect of ophiopogon-polysaccharide on adiponectin (APN) in gestational diabetic mellitus rat. The model of gestational diabetes mellitus rat were established with streptozotocin by intraperitoneal injection. Model rats were randomly divided into ophiopogon-polysaccharide 125 mg/kg group, 250 mg/kg group, 500 mg/kg group, GDM group and normal pregnancy group (n=10). Ophiopogon-polysaccharide was given by intragastric administration for 14 days. The fasting blood glucose levels of rats at the 0, 7, 14 day were detected respectively. The serum insulin level and APN in fat tissue and placenta were detected at the 14 day. The fasting blood glucose level, serum insulin level and APN mRNA in fat tissue and placenta were significantly decreased in gestational diabetes rats treated by ophiopogon-polysaccharide compared with model group (P < 0.05). Ophiopogon-polysaccharide could decrease the fasting blood glucose level and serum insulin level, and improve APN mRNA in fat tissue and placenta.


T cell receptor specificity for major histocompatibility complex proteins.
The ligands for alpha beta T cell receptors (alphabetaTCRs) are usually major histocompatibility complex (MHC) proteins bound to peptides. Although there is evidence that T cell receptor variable regions have been selected evolutionarily to bind MHC, the rules governing this interaction have not previously been apparent. However, recent solved structures of T cell receptors with related variable regions bound to MHC plus peptides suggest that some amino acids in variable region CDR1 and CDR2s almost always react in a consistent way with MHC. These amino acids may therefore have been selected evolutionarily to predispose T cell receptors toward recognition of MHC ligands.


Measures of adiposity and risk of stroke in China: a result from the Kailuan study.
The objective of this study was to explore the association between adiposity and risk of incident stroke among men and women. We studied the relationship between adiposity and stroke among 94,744 participants (18-98 years old) in the Kailuan study. During a follow-up of 4 years, 1,547 ischemic or hemorrhagic strokes were recorded. Measurements of adiposity included body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHpR), and waist-to-height ratio (WHtR). Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated from Cox regression models and each model fit was assessed using -2log-likelihood. Every measurement of adiposity was associated with the risk for total stroke and ischemic stroke, but not for hemorrhagic stroke. After adjusting for confounders and intermediates, the HR (comparing the mean of the highest quintile with that of the lowest quintile) for total stroke was 1.34(1.13-1.60) for BMI, 1.26(1.06-1.52) for WC, 1.29(1.08-1.56) for WHpR, and 1.38(1.15-1.66) for WHtR. The HR for ischemic stroke was 1.52(1.24-1.88) for BMI, 1.46(1.17-1.81) for WC, 1.40(1.12-1.74) for WHpR, and 1.62(1.29-2.04) for WHtR. The model fit for each of the indices was similar. Adiposity increases the total risk of stroke and ischemic stroke, but not of hemorrhagic stroke. No clinically meaningful differences among the associations between BMI, WC, WHpR, and WHtR and stroke incidence were identified in this study.


Opposing effects on mitochondrial membrane potential by malonate and levamisole, whose effect on cell-mediated mineralization is antagonistic.
The act of chondrocyte preparation for primary, enchondral, mineralization is associated with a decline in mitochondrial respiration toward the end of the proliferative zone and the hypertrophic zone in the growth plate. Dexamethasone (Dex)-stimulated cultures of rat marrow stroma constitute a differentiation model simulating, in its energy metabolism, chondrocyte mineralization. In this model, early inhibition of succinate dehydrogenase (SDH) enriches the culture with mineralizing cells, whereas levamisole inhibits mineralization. Dex also increases mitochondrial membrane potential in stromal cells, especially on days 7-8 of stimulation. In the present study, suicide inhibition of SDH, by nitropropionic acid (NPA), in Dex-stimulated cells showed a dose-dependent increase in day 21 mineralization; the maximal effect was induced on days 2-4 of stimulation. Mineralization under 2-day-long exposure to NPA showed a similar trend to the previously studied effect of continuous exposure to malonate applied between days 3-11. Unlike malonate, the effect of NPA required its presence in the cultures for only 2 days and resulted in higher mineralization than that seen under 8 days of malonate. NPA delineated a period, days 2/4 to 7/9, in which inhibition of succinate oxidation is necessary to augment mineralization. During this period, NPA also exhibited OPC selection capacity. Early application of levamisole, under conditions previously shown to decrease day 21 mineralization, maintained mitochondrial membrane potential at the beginning of Dex stimulation but decreased or had little effect on it during days 5-10. By contrast, malonate previously found to increase day 21 mineralization decreased the membrane potential at the beginning of Dex stimulation but increased it later on day 7, or during days 5-10. These results indicate that during osteoprogenitor differentiation, before the mineralization stage, a surge in mitochondrial inner membrane potential during late matrix maturation may be a marker that heralds the extracellular matrix mineralization.


Relationship between phase I study duration and symptom burden.
Phase I clinical trials are critical to development of cancer therapeutics. Adverse events (AEs) and symptom burden contribute to early treatment withdrawal, and it is often difficult to ascertain whether these events are disease- or treatment-related. Regardless, early withdrawal may delay determination of the effectiveness of potential new therapies. We sought to characterize the reasons for early treatment termination to identify potential modifiable events. A retrospective chart review was conducted on solid tumor patients enrolled in institutional phase I clinical trials from 2003 to 2013 through the Case Comprehensive Cancer Center. Two hundred fifty-five patients were included in the analysis. The mean duration on study was 78.4 days (SD 63.4 days), and 23% of the patients were on study ≤ 30 days. Patients experienced an average of 25.1 AEs, of which 46.9% were non-laboratory. Constitutional symptoms (29.3%), gastrointestinal symptoms (24%), and pain (12.8%) were the most common non-laboratory AEs. Disease progression (57.6%) was the most common reason for study discontinuation, followed by adverse events (16.5%). Approximately 13% of the patients discontinued treatment for other reasons, of which 41.7% were identified as related to symptom burden on further review. Increased rates of AEs negatively correlated with duration on study (r = - 0.331; p < 0.01). AEs may lead to early termination of trial participation and confound clinical assessment of investigational treatments. Designing interventions to reduce AE burden may extend duration on trial, affect the recommended phase II dose, and benefit the quality of life of participants on phase I trials.


Intrathecal CGS-26303 Pretreatment Attenuates Spinal Nerve Ligation-Induced Neuropathic Pain in the Spinal Cord.
Matrix metalloproteinase (MMPs) and endothelin-1 may prove to be important in the generation of pain induced by inflammation and nerve lesion. This study aimed to investigate the relationship between endothelin receptors and MMPs. Male Sprague-Dawley rats (250-300 g) were divided into 5 groups: a normal (control) group; an L5 spinal nerve ligation (SNL) group; a CGS-26303 IT + L5 SNL group; a BQ-123 IT + L5 SNL group; and a BQ-788 IT + L5 SNL group. The expression of glial fibrillary acidic protein, endothelin-A receptor (ETAR), endothelin-B receptor, MMP-2, and MMP-9 in the ipsilateral L5 dorsal root ganglion (DRG) and the activation of microglia and astrocytes in the L5 spinal dorsal horn (SDH) were quantified by immunofluorescence and Western blotting. Intrathecal pretreatment with CGS-26303 significantly attenuated the hyperalgesic and mechanical responses induced by SNL for 4 days, whereas BQ-123 administration alleviated the hyperalgesia only for 3 hours and mechanical allodynia for only 1 hour. Pretreatment with CGS-26303 significantly down-regulated the glial fibrillary acidic protein, ET-A, MMP-2, and MMP-9 expressions in DRG and their effect lasted for 6 hours, 1 day, 7 days, and 1 day, respectively. By immunofluorescence and Western blotting, there was colocalization of ETAR and MMP-9 in the DRG neurons, whereas MMP-2 was expressed in DRG satellite cells. Furthermore, CGS-26303 treatment also reduced SNL-induced microglia and astrocyte activation on the SDH for 7 days. In this study, CGS-26303 can attenuate SNL-induced neuropathic pain by down-regulating MMP-9, MMP-2, and ETAR expressions in the DRG and by glia cell activation in the SDH.


Lipopolysaccharides of Vibrio cholerae: III. Biological functions.
This review presents the salient features of the biological functions including the (i) endotoxic activities, (ii) antigenic properties, (iii) immunological responses to and (iv) phage receptor activities of the Vibrio cholerae lipopolysaccharides (LPS). The biological functions of the capsular polysaccharide (CPS) of V. cholerae have also been discussed briefly as a relevant topic. The roles of LPS and other extracellular polysaccharides in the (i) intestinal adherence and virulence of the vibrios and (ii) the biofilm formation by the organisms have been analysed on the basis of the available data. Every effort has been made to bring out, wherever applicable, the lacunae in our knowledge. The need for the continuous serogroup surveillance and monitoring of the environmental waters and the role of LPS in the designing of newer cholera vaccines has been discussed briefly in conclusion.


[Treatment of sudden sensorineural hearing loss (SSHL) with HELP-apheresis: our experience].
In a specific group of patients affected by sudden sensorineural hearing loss (SSHL) with high plasma levels of LDL-cholesterol and/or fibrinogen, HELP-apheresis treatment makes a difference in hearing recovery and is a further option available in SSHL therapy.


Effect on Nail Structure and Transungual Permeability of the Ethanol and Poloxamer Ratio from Cyclodextrin-Soluble Polypseudorotaxanes Based Nail Lacquer.
Aqueous-based nail lacquers have shown potential in promoting the diffusion of drugs into the nail. In our laboratory, we have recently developed a transungual delivery system based on an aqueous dispersion of cyclodextrin-poloxamer soluble polypseudorotaxanes, supramolecular host-guest assemblies that improves the drug permeation into the nail. However, the high-water content and the rheological and adhesive properties of this lacquer negatively affect properties that play a fundamental role in the patients' acceptance such as stickiness, nail film formation or drying rate, properties. In this work, we have optimized the composition of these lacquers to improve these properties whilst maintaining good drug permeation profiles. Incorporating ethanol into the vehicle and reducing the proportion of Poloxamer 407 (PL), provided a good strategy. The use of hydro-ethanolic mixtures (>50% ethanol) and the reduction of the poloxamer concentration significantly improved the lacquer drying speed by reducing the stickiness and promoting film formation on the nail surface. Additionally, in a surprising way, the use of hydro-ethanolic vehicles further enhanced the permeation of ciclopirox olamine and clobetasol propionate, used for the treatment of onychomycosis and nail psoriasis respectively, into the nail and hooves.


Pyrazoles containing thiophene, thienopyrimidine and thienotriazolopyrimidine as COX-2 selective inhibitors: Design, synthesis, in vivo anti-inflammatory activity, docking and in silico chemo-informatic studies.
New thiophene and annulated thiophene pyrazole hybrids were synthesized and screened for their in vitro COX-1/COX-2 enzymatic inhibition and in vivo anti-inflammatory activities. All compounds were more COX-2 selective inhibitors than COX-1 with compound 13 exhibiting the highest COX-2 selectivity index. Compounds 3, 6a, 9 and 11 were the most promising in the acute anti-inflammatory assay while compounds 3, 5, 6a, 6c, 9, 10, 11 and 13 exerted promising anti-inflammatory activity in the sub-acute anti-inflammatory assay. Compounds 3, 6a, 6c, 9, 10 and 11 were evaluated for their ED50 values and were more potent than diclofenac sodium while compounds 6a, 6c and 9 were of greater potency than celecoxib with compound 6a being the most potent showing ED50 = 0.033 mmol/kg. These compounds were non-toxic and proved to be gastrointestinal safe compared to indomethacin, diclofenac sodium and celecoxib. Docking studies into COX-2 active site (PDB code 3LN1) revealed that compounds 3, 6a, 6c, 9, 10, 11 and 13 had binding modes and energies comparable to that of celecoxib. Compounds 3, 9, 10 and 11 complied with Lipinski's RO5 while compounds 6a and 6c showed one violation whereas compound 13 deviated by 2 violations. Compounds 6a, 6c and 13 showed 100% plasma protein binding (PPB) and showed no aqueous solubility while compounds 3, 10 and 11 demonstrated the best drug likeness model scores. Therefore, the thiophene analog 3 and the thienopyrimidine derivatives 10 and 11 are promising anti-inflammatory candidates that exert moderate selective COX-2 inhibition with acceptable physicochemical properties.


The influence of the thylakoid membrane surface properties on the distribution of ions in chloroplasts.
Thylakoid membranes isolated from peas have been subjected to ionic analyses using the technique of neutron activation. This has allowed the analyses of K+, Na+, Mg2+, Ca2+ and Cl- to be measured simultaneously on the same sample. By varying the ionic composition of the suspending medium it has been shown that these chloroplast membranes have no obvious chemical specificity for the inorganic cations studied and that the major controlling factor is the electrostatic neutralization of the surface negative charges. In agreement with the Gouy-Chapman theory and for the conditions used, divalent cations were preferentially attracted to the membrane surface. This finding, together with the ionic analysis of the unwashed thylakoids and of isolated intact chloroplasts, indicated that the major physiological surface cation is Mg2+ and that K+ is probably the main inorganic cation of the stroma. This conclusion is discussed in terms of counterion movement in response to light induced proton pumping at the thylakoid membrane.


[Analysis of the cardiointervalograms of neurosurgical patients in the postoperative period].
The 24-hour dynamics of the oscillatory components of the heart rhythm in neurosurgical patients in the postoperative period is shown. The peculiarities of the wave structure of the spectrum density graph depending on the localization of the pathological process and the severity of the postoperative course were revealed.


The effect of random dispersal on competitive exclusion - A review.
Does a high dispersal rate provide a competitive advantage when risking competitive exclusion? To this day, the theoretical literature cannot answer this question in full generality. The present paper focuses on the simplest mathematical model with two populations differing only in dispersal ability and whose one-dimensional territories are spatially segregated. Although the motion of the border between the two territories remains elusive in general, all cases investigated in the literature concur: either the border does not move at all because of some environmental heterogeneity or the fast diffuser chases the slow diffuser. Counterintuitively, it is better to randomly explore the hostile enemy territory, even if it means highly probable death of some individuals, than to "stay united". This directly contradicts a celebrated result on the intermediate competition case, emphasizing the importance of the competition intensity. Overall, the larger picture remains unclear and the optimal strategy regarding dispersal remains ambiguous. Several open problems worthy of a special attention are raised.


Burkitt's lymphoma in Iraq. Clinical and pathological study of forty-seven patients.
The clinical and pathological features of 47 patients with Burkitt's lymphoma seen at the University of Baghdad Teaching Hospital over the years 1969-1977 are described. There were 30 males and 17 females with a mean age of 7.5 years. All patients presented with advanced disease; 44 were in Stage III and 3 in Stage IV, (1 with central nervous system involvement; 1 with bone-marrow involvement; 1 presented as acute leukaemia). The abdomen, with or without other sites, was involved in 42 patients. Thirty-four patients died within 18 months, 11 in the immediate post-operative period. Cyclophosphamide in variable dosages was administered to 29 patients with a good response in 15. The 3 patients with Stage IV disease died with poor response to therapy. Thus, in Iraq, a non-endemic area for the disease, Burkitt's lymphoma seems to have somewhat different clinical and pathological features from the endemic (African), or the rare, sporadic disease reported elsewhere.


Using Machine Learning to Establish Predictors of Mortality in Patients Undergoing Laparotomy for Emergency General Surgical Conditions.
Patients undergoing laparotomy for emergency general surgery (EGS) conditions, constitute a high-risk group with poor outcomes. These patients have a high prevalence of comorbidities. This study aims to identify patient factors, physiological and time-related factors, which place patients into a group at increased risk of mortality. In a retrospective analysis of all patients undergoing an emergency laparotomy at Greys Hospital from December 2012 to 2018, we used decision tree discrimination to identify high-risk groups. Our cohort included 1461 patients undergoing a laparotomy for an EGS condition. The mortality rate was 12.4% (181). Nine hundred and ten patients (62.3%) had at least one known comorbidity on admission. There was a higher rate of comorbidities among those that died (154; 85.1%). Patient factors found to be associated with mortality were the age of 46 years or greater (p < 0.001), current tuberculosis (p < 0.001), hypertension (p = 0.014), at least one comorbidity (0.006), and malignancy (0.033). Significant physiological risk factors for mortality were base excess less than -6.8 mmol/L (p < 0.001), serum urea greater than 7.0 mmol/L (p < 0.001) and waiting time from admission to operation (p = 0.014). In patients with an enteric breach, those younger than 46 years and a Shock Index of more than 1.0 were high-risk. Patients without an enteric breach were high-risk if operative duration exceeded 90 min (p = 0.004) and serum urea exceeding 7 mmol/dl (p = 0.016). In EGS patients, patient factors as well as physiological factors place patients into a high-risk group. Identifying a high-risk group should prompt consideration for an adjusted approach that ameliorates outcomes.


Inhibition of gluconeogenesis by vanadium and metformin in kidney-cortex tubules isolated from control and diabetic rabbits.
Effect of vanadyl acetylacetonate (VAc) and metformin on gluconeogenesis has been studied in isolated hepatocytes and kidney-cortex tubules of rabbit. Glucose formation from alanine+glycerol+octanoate, pyruvate or dihydroxyacetone was inhibited by 50-80% by 100 microM VAc or 500 microM metformin in renal tubules of control and alloxan-diabetic animals, while the inhibitory action of these compounds in hepatocytes was less pronounced (by about 20-30%). In contrast to VAc, metformin increased the rate of lactate formation by about 2-fold in renal tubules incubated with alanine+glycerol+octanoate. In view of VAc-induced changes in intracellular gluconeogenic intermediates and gluconeogenic enzyme activities, it is likely that this compound may decrease fluxes through pyruvate carboxylase, phosphoenolpyruvate carboxykinase, fructose-1,6-bisphosphatase and glucose-6-phosphatase. In contrast to VAc, metformin-induced decrease in renal gluconeogenesis may result from a decline of cytosolic oxaloacetate level and consequently PEPCK activity. Following 6 days of VAc administration (1.275 mg Vkg(-1) body weight daily) the blood glucose level in alloxan-diabetic rabbits was normalised while blood glucose changes in control animals were not observed. On the contrary, in diabetic animals treated for 6 days with metformin (200 mg kg(-1) body weight day(-1)) a high blood glucose level was maintained. Unfortunately, VAc-treated control and diabetic rabbits exhibited elevated serum urea and creatinine levels. In VAc-treated animals vanadium was accumulated in kidney-cortex up to 7.6+/-0.6 microg Vg(-1) dry weight. In view of a potential vanadium nephrotoxicity a therapeutic application of vanadium compounds needs a critical re-evaluation.


Effects of propranolol pretreatment on cerebral blood flow, oxygen uptake and catecholamines during metabolic acidosis following E. coli endotoxin in dogs.
After an intravenous injection of E. coli endotoxin in dogs a decrease in cerebral blood flow (CBF) and an increase in cerebral metabolic rate of oxygen (CMRo2) have been shown to occur. In metabolic acidosis following endotoxin CMRo2 increased with decreasing pH. A possible explanation for the increased CMRo2 after endotoxin and metabolic acidosis seems to be a damage of the blood-brain barrier (BBB) by endotoxin. This gives possibilities for a leakage of hydrogen ions and circulating monoamines from the blood to the brain, thus affecting the cerebral blood flow and metabolism. The effects of an E. coli endotoxin injection on CBF and CMRo2 during metabolic acidosis and beta-adrenoceptor blockade were studied in eight anaesthetized dogs. All the dogs were pretreated with propranolol (PPL), per os 12.5 mg.kg-1 twice a day for one week. Metabolic acidosis (pH 7.01-7.30) was achieved by an intravenous infusion of hydrochloric acid. Endotoxin E. coli lipopolysaccharide O 111:B 4 was given as an intravenous injection of 1 mg.kg-1 bodyweight over a 5 min period. Another five animals, published earlier, with the same experimental protocol but without PPL, constituted a control group. After endotoxin no increase in CMRo2 or CBF was observed with increasing acidosis in the PPL-group. In the control group, after endotoxin, both CBF and CMRo2 increased with decreasing pH. This resulted in a significant difference in both CBF and CMRo2 between the groups in the pH range 7.01-7.15. The present results indicate that the increase in CMRo2 and CBF with metabolic acidodis in endotoxinaemia is mediated via beta-adrenoceptors.


Impaired synthesis or cellular storage of norepinephrine, dopamine, and 5-hydroxytryptamine in human inflammatory bowel disease.
The present study was aimed at evaluating the extent of dysfunction of the enteroendocrine and enteric nervous system, as indicated by changes in tissue levels of monoamines (dopamine, DA; norepinephrine, NE; 5-hydroxytryptamine, 5-HT) and their precursors and metabolites in the colonic mucosa of patients afflicted with ulcerative colitis (UC, N = 21) and Crohn's disease (CD, N = 22). In CD, but not in UC, NE tissue levels in both the noninflamed and inflamed colonic mucosa were markedly lower than in control subjects (N = 16). In the inflamed mucosa of CD and in UC patients levels of L-DOPA were twice those in controls. DA levels in the inflamed mucosa of CD and UC patients were markedly lower than in controls. This resulted in significant reductions in DA/L-DOPA tissue ratios, a rough measure of L-amino acid decarboxylase activity. 5-HT levels in the inflamed mucosa of CD and UC patients were markedly lower than in controls. In conclusion, intestinal cellular structures responsible for the synthesis and storage of DA, NE, and 5-HT may have been affected by the associated inflammatory process in both CD and UC.


Liver regeneration using decellularized splenic scaffold: a novel approach in tissue engineering.
The potential application of decellularized liver scaffold for liver regeneration is limited by severe shortage of donor organs. Attempt of using heterograft scaffold is accompanied with high risks of zoonosis and immunological rejection. We proposed that the spleen, which procured more extensively than the liver, could be an ideal source of decellularized scaffold for liver regeneration. After harvested from donor rat, the spleen was processed by 12-hour freezing/thawing x 2 cycles, then circulation perfusion of 0.02% trypsin and 3% Triton X-100 sequentially through the splenic artery for 32 hours in total to prepare decellularized scaffold. The structure and component characteristics of the scaffold were determined by hematoxylin and eosin and immumohistochemical staining, scanning electron microscope, DNA detection, porosity measurement, biocompatibility and cytocompatibility test. Recellularization of scaffold by 5 x 10(6) bone marrow mesenchymal stem cells (BMSCs) was carried out to preliminarily evaluate the feasibility of liver regeneration by BMSCs reseeding and differentiation in decellularized splenic scaffold. After decellularization, a translucent scaffold, which retained the gross shape of the spleen, was generated. Histological evaluation and residual DNA quantitation revealed the remaining of extracellular matrix without nucleus and cytoplasm residue. Immunohistochemical study proved the existence of collagens I, IV, fibronectin, laminin and elastin in decellularized splenic scaffold, which showed a similarity with decellularized liver. A scanning electron microscope presented the remaining three-dimensional porous structure of extracellular matrix and small blood vessels. The porosity of scaffold, aperture of 45.36 +/- 4.87 μm and pore rate of 80.14% +/- 2.99% was suitable for cell engraftment. Subcutaneous implantation of decellularized scaffold presented good histocompatibility, and recellularization of the splenic scaffold demonstrated that BMSCs could locate and survive in the decellularized matrix. Considering the more extensive organ source and satisfying biocompatibility, the present study indicated that the three-dimensional decellularized splenic scaffold might have considerable potential for liver regeneration when combined with BMSCs reseeding and differentiation.


Frequency of lower respiratory tract infections in relation to adaptive immunity in children with Down syndrome compared to their healthy siblings.
Children with Down syndrome (DS) experience respiratory tract infections (RTIs) more frequently than healthy children. We investigated whether this is related to different immunological characteristics associated with DS. The study group consisted of 22 children with DS and 22 of their healthy, age-range matched siblings. Data were collected on infections and hospitalizations because of lower RTIs. Immunoglobulin and IgG subclass levels in blood, as well as lymphocyte and T cell (subset) counts, were determined. The children with DS had a significantly higher frequency of lower RTIs and related hospitalization than their siblings. We also found significantly reduced IgG2 levels as well as significantly lower counts of total lymphocytes, CD4(+) T lymphocytes, CD4(+) invariant natural killer (iNKT) cells and regulatory T cells in the DS group. In children with DS, reduced levels of IgG2, total lymphocytes, T lymphocytes, iNKT cells and regulatory T cells might contribute to their higher susceptibility to lower RTIs.


Virally programmed extracellular vesicles sensitize cancer cells to oncolytic virus and small molecule therapy.
Recent advances in cancer therapeutics clearly demonstrate the need for innovative multiplex therapies that attack the tumour on multiple fronts. Oncolytic or "cancer-killing" viruses (OVs) represent up-and-coming multi-mechanistic immunotherapeutic drugs for the treatment of cancer. In this study, we perform an in-vitro screen based on virus-encoded artificial microRNAs (amiRNAs) and find that a unique amiRNA, herein termed amiR-4, confers a replicative advantage to the VSVΔ51 OV platform. Target validation of amiR-4 reveals ARID1A, a protein involved in chromatin remodelling, as an important player in resistance to OV replication. Virus-directed targeting of ARID1A coupled with small-molecule inhibition of the methyltransferase EZH2 leads to the synthetic lethal killing of both infected and uninfected tumour cells. The bystander killing of uninfected cells is mediated by intercellular transfer of extracellular vesicles carrying amiR-4 cargo. Altogether, our findings establish that OVs can serve as replicating vehicles for amiRNA therapeutics with the potential for combination with small molecule and immune checkpoint inhibitor therapy.


DR antigens expressed on tumor cells do not contribute to the blastogenetic response of autologous T cells.
Tumor cell suspensions prepared from surgical specimens were characterized for cellular composition and reactivity with monoclonal antibodies detecting T lymphocytes, monocytes, and the monomorphic determinants of DR molecules (antigens encoded by the D region of the major histocompatibility complex in man). About half the adenocarcinoma preparations contained tumor cells which expressed DR antigens. Lymphocytes of certain patients were stimulated in vitro by the autologous tumor cells, and this was independent of the expression of DR antigens on the tumor cells. In addition, pretreatment of the stimulator tumor cells with anti-DR Mab (monoclonal antibody) had only marginal effect on their stimulatory potential. In contrast, when the same tumor cells were used as stimulators of allogeneic lymphocytes, proliferation was more often seen with DR-positive tumors and the reaction was often inhibited by the anti-DR Mab treatment. There were exceptions, however, which suggest that other DR antigens not detected by the reagents used may have been expressed on these cells. The allostimulatory capacity of the tumor cells was usually weak and did not occur with all responder lymphocytes. It is important to note that stimulation of autologous lymphocytes could occur with tumor preparations that did not elicit allogeneic response. Thus, the in vitro stimulation of autologous blood-derived T cells by suspensions of unpropagated cells separated from solid tumors reflects the sensitization state of the patients against their tumor cells.


Effects of SCH 23390 and sulpiride on the behaviors evoked by amphetamine and apomorphine in adult cats.
1. The aim of the present study was to analyze whether the dopaminergic D1 and D2 receptors are involved in the production of the behaviors evoked by parenteral administration of amphetamine and apomorphine in adult cats. 2. Fifteen mongrel cats of both sexes were injected, in separate sessions, with 2.5 mg/kg of amphetamine and 2.0 mg/kg of apomorphine. The D1 receptor blocker, SCH 23390 was administered (0.3 mg/kg i.p.) and after 60 min, amphetamine and apomorphine were again injected on different days. The same procedure was carried on with sulpiride in two doses (20 and 30 mg/kg i.p.). The behaviors induced by the two dopaminergic drugs, before and after the receptor blocker administration were respectively compared. The Wilcoxon signed rank test was employed for statistical analysis. Three independent observers recorded the behaviors. 3. SCH 23390 and sulpiride produced per se hypomotility and sedation, effects that were considered when analysing the results. Some of the behaviors produced by amphetamine (pupillary dilation, head movements) were slightly modified by both receptor blockers. SCH 23390 only modified the licking behavior produced by apomorphine. In contrast, sulpiride blocked almost all the behaviors elicited by apomorphine, especially when the 30 mg/kg dose was administered. It is concluded that the behaviors produced by the 2 mg/kg dose of apomorphine are evoked by its binding to the post-synaptic dopaminergic D2 receptors and blocked by sulpiride.


Pulsar sub-pulses and the emission process.
This article describes another regular phenomenon in the sub-pulse behaviour of pulsars. The drift speed of successive sub-pulses follows a sawtooth pattern with a linearly increasing drift speed and sudden jumps as the speed drops to repeat the cycle.


Indocyanine green pharmacokinetics calculations using Lotus 123 spreadsheet.
Indocyanine green (ICG; Cardio Green, Hynson, Westcott & Dunning, Baltimore, MD) is a cholephilic dye that is commonly used as a liver function test. In order to obtain the pharmacokinetic values of ICG needed for liver function determinations, a linear and a log-linear regression must be done in addition to other calculations. Results can be obtained graphically, but are not as accurate as mathematical calculations. To obtain accurate results and expedite calculation time, a program was developed using the Lotus 123 spreadsheet program (Lotus 123, Lotus Development Corporation, Cambridge, MA) and an IBM compatible computer to do these calculations.


Does a redox cycle provide a mechanism for setting the capacity of neuroglobin to protect cells from apoptosis?
We hypothesize that the various, previously reported, reactivities of neuroglobin with redox partners and oxygen provide for the establishment of a redox cycle within cells, such as neurons and retinal rod cells. Using native cell lysates, from cultured human cells of neuronal origin, we have estimated the rate of reduction of the oxidized form of neuroglobin in vivo. Furthermore we provide evidence that the cytosol of these cells contains factors (presumably enzymes) capable of employing either glutathione or NADH as re-reductants of ferric neuroglobin. Taken in conjunction with previous rate data, for the various redox reactions of neuroglobin, this information allows us to set up a computer model to estimate the steady state cellular level of the antiapoptotic ferrous form of neuroglobin. This model indicates that the steady state level of antiapoptotic neuroglobin is very sensitive to the cellular oxygen tension and moderately sensitive to the redox status of the cell. Further analysis indicates that such a system would be capable of significant modification, on the seconds time scale, following hypoxic transition, as is likely in stroke. We hypothesize that this mechanism might provide a moderately rapid mechanism for adjusting the antiapoptotic status of a cell, whilst the reaction of neuroglobin with mitochondrial cytochrome c provides a very rapid, but limited, capacity to intervene in the apoptotic pathway.


Ketogenic diet alleviates brain iron deposition and cognitive dysfunction via Nrf2-mediated ferroptosis pathway in APP/PS1 mouse.
Progressive cognitive decline and increased brain iron deposition with age are important features of Alzheimer's disease. Previous studies have found that the short-term ketogenic diet has neuroprotective effects in a variety of neurodegenerative diseases, but the effects of an early and long-term ketogenic diet on brain iron content and cognition of Alzheimer's disease have not been reported. In our study, 8-week-old APP/PS1 mice were given a 12-month ketogenic or standard diet, while C57BL/6 mice matched with the age and genetic background of APP/PS1 mice were used as normal controls to be given a standard diet for the same length of time. We found that 12 months of an early ketogenic diet improved the impaired learning and memory ability of APP/PS1 mice. The improvement of cognitive function may be related to the reduction of amyloid-beta deposition and neuronal ferroptosis. The mechanism was achieved by the regulation of ferroptosis-related pathways after activation of nuclear factor erythroid 2-related factor 2 by ketogenic diet-induced elevated β-hydroxybutyrate. In addition, blood biochemical results showed that compared with the standard diet group of the disease, although the early and long-term ketogenic diet increased blood lipids to some extent, it seemed to reduce liver, renal, and myocardial damage caused by genetic differences. This will provide a piece of positive evidence for the early and long-term use of ketogenic diets in people at risk of Alzheimer's disease.


Effectiveness and safety of empagliflozin in routine care patients: Results from the EMPagliflozin compaRative effectIveness and SafEty (EMPRISE) study.
To investigate effectiveness and safety outcomes among patients with type 2 diabetes (T2D) initiating empagliflozin versus dipeptidyl peptidase-4 (DPP-4) inhibitor treatment across the broad spectrum of cardiovascular risk. In a population-based cohort study we identified 39 072 pairs of 1:1 propensity score-matched adult patients with T2D initiating empagliflozin or DPP-4 inhibitors, using data from 2 US commercial insurance databases and Medicare between August 2014 and September 2017. The primary outcomes were a composite of myocardial infarction (MI)/stroke, and hospitalization for heart failure (HHF). Safety outcomes were bone fractures, lower-limb amputations (LLAs), diabetic ketoacidosis (DKA), and acute kidney injury (AKI). We estimated pooled hazard ratios (HRs) and 95% confidence intervals (CIs) adjusting for more than 140 baseline covariates. Study participants had a mean age of 60 years and only 28% had established cardiovascular disease. Compared to DPP-4 inhibitors, empagliflozin was associated with similar risk of MI/stroke (HR 0.99 [95% CI 0.81-1.21]), and lower risk of HHF (HR 0.48 [95% CI 0.35-0.67] and 0.63 [95% CI 0.54-0.74], based on a primary and any heart failure discharge diagnosis, respectively). The HR was 0.52 (95% CI 0.38-0.72) for all-cause mortality (ACM) and 0.83 (95% CI 0.70-0.98) for a composite of MI/stroke/ACM. Empagliflozin was associated with a similar risk of LLA and fractures, an increased risk of DKA (HR 1.71 [95% CI 1.08-2.71]) and a decreased risk of AKI (HR 0.60 [95% CI 0.43-0.85]). In clinical practice, the initiation of empagliflozin versus a DPP-4 inhibitor was associated with a lower risk of HHF, ACM and MI/stroke/ACM, a similar risk of MI/stroke, and a safety profile consistent with documented information.


DFT study of the V(IV)/V(V) oxidation mechanism in the presence of N-hydroxyacetamide.
The oxidation mechanism of V(IV)/V(V) in the presence of N-hydroxyacetamide (acetohydroxamic acid, HL) in aqueous solution has been investigated using density functional theory (DFT) calculations aiming to contribute to the understanding of this process at a molecular level. The mechanism proposed involves formation of the *OH, *OOH, H2O2 radicals and complexes formed from the interaction of these species with VOL2 complex. The Gibbs free energy of each step of the mechanism has been evaluated. The solvation energy has been estimated by means of united atoms Hartree-Fock/polarizable continuum method (UAHF/PCM). The Gibbs free energy of the global reaction of the V(IV)/V(V) oxidation has been estimated and compared with the available experimental equilibrium constant. The difference between the calculated and experimental estimates for the reaction energy of the global equation is about 1.5 kcal mol(-1). The thermodynamic profile of the reaction mechanism has been provided and discussed in terms of the possible intermediates. The influence of the ligand and the reaction rate in terms of the steady-state approximation has been briefly discussed.


Omega-3 polygenic score protects against altered eating behavior in intrauterine growth-restricted children.
Alterations in eating behavior are common in infants with intrauterine growth restriction (IUGR); omega-3 polyunsaturated fatty acids (PUFA) could provide protection. We hypothesized that those born IUGR with a genetic background associated with increased production of omega-3-PUFA will have more adaptive eating behaviors during childhood. IUGR/non-IUGR classified infants from MAVAN and GUSTO cohorts were included at the age of 4 and 5 years, respectively. Their parents reported child's eating behaviors using the child eating behavior questionnaire-CEBQ. Based on the GWAS on serum PUFA (Coltell 2020), three polygenic scores were calculated. Significant interactions between IUGR and polygenic score for omega-3-PUFA on emotional overeating (β = -0.15, P = 0.049 GUSTO) and between IUGR and polygenic score for omega-6/omega-3-PUFA on desire to drink (β = 0.35, P = 0.044 MAVAN), pro-intake/anti-intake ratio (β = 0.10, P = 0.042 MAVAN), and emotional overeating (β = 0.16, P = 0.043 GUSTO) were found. Only in IUGR, a higher polygenic score for omega-3-PUFA associated with lower emotional overeating, while a higher polygenic score for omega-6/omega-3-PUFA ratio was associated with a higher desire to drink, emotional overeating, and pro-intake/anti-intake. Only in IUGR, the genetic background for higher omega-3-PUFA is associated with protection against altered eating behavior, while the genetic score for a higher omega-6/omega-3-PUFA ratio is associated with altered eating behavior. A genetic background related to a higher polygenic score for omega-3 PUFA protected infants born IUGR against eating behavior alterations, while a higher polygenic score for omega-6/omega-3 PUFA ratio increased the risk of having eating behavior alterations only in infants born IUGR, irrespective of their adiposity in childhood. Genetic individual differences modify the effect of being born IUGR on eating outcomes, increasing the vulnerability/resilience to eating disorders in IUGR group and likely contributing to their risk for developing metabolic diseases later in life.


The role of C-type lectin receptors in immune homeostasis.
C-type lectin receptors (CLRs) are important pathogen pattern recognition molecules that recognize carbohydrate structures. Upon ligand binding, CLRs induce a variety of cellular responses, such as respiratory burst, production of cytokines and chemokines, and consequently shaping the adaptive immune responses. Recent frontier studies have demonstrated that CLRs play a significant role in development of anti-inflammatory immune responses and maintenance of host immune-homeostasis. In this review we describe the major CLRs involved in production of IL-10 by immune-related cells and functional maturation of regulatory T cells. In addition, we discuss the potential role of CLRs signaling in regulating intestinal immune-homeostasis and inflammation. Further understanding of the precise role for these receptors on immunoregulatory cells will provide unexpected opportunities for developing new therapies for inflammatory diseases.


Stability of predictors of mortality after spinal cord injury.
Cohort study. To identify the stability of socio-environmental, behavioral and health predictors of mortality over an 8-year time frame. Data were analyzed at a large medical university in the Southeast United States of America (USA). Adults with residual impairment from a spinal cord injury (SCI) who were at least 1-year post-injury at assessment were recruited through a large specialty hospital in the Southeast USA. A total of 1209 participants were included in the final analysis. A piecewise exponential model with two equal time intervals (8 years total) was used to assess the stability of the hazard and the predictors over time. The hazard did significantly change over time, where the hazard in the first time interval was significantly lower than the second. There were no interactions between the socio-environmental, behavior or health factors and time, although there was a significant interaction between age at injury (a demographic variable) and time. These results suggest there is stability in the association between the predictors and mortality, even over an 8-year time period. Results reinforce the use of historic variables for prediction of mortality in persons with SCI.


Microplastic pollution in water environment of typical nature reserves and scenery districts in southern China.
Microplastics were frequently detected in the ocean, freshwater environment and wastewater treatment plants. This study aims to fill up the knowledge gap of microplastic distribution in nature reserves and scenery districts. Microplastic samples were collected, the distribution characteristics were analyzed with a stereoscopic microscope and a Fourier transform infrared spectrometer, and the ecological risks of microplastic pollution were calculated. Microplastics were detected in all the collected water samples and the average abundances of microplastics in the surface water of eleven investigated nature reserves and scenery districts ranged from 542 to 5500 items/m3. The degrees of microplastic pollution of all the surveyed nature reserves and scenery districts were classified as hazard level I. Fiber microplastics represented the largest average proportion (67.4 %) and 91.7 % of the detected microplastics were smaller than 2 mm. Corresponding to the frequent detection of fiber microplastics, cotton was the most abundant (25.5 %) polymer type of the suspected microplastics, followed by polyamide (PA, 20.6 %), polyester (PET, 17.0 %), and cellulose (15.6 %). For the ecological risk of the microplastic polymers, six, two and three nature reserves and scenery districts were defined to be at hazard level I, II and III, respectively. In brief, microplastic pollution occurred in all the surveyed nature reserves/scenery districts and posed different degrees of ecological risks.


Rheumatoid arthritis and growth retardation in children: treatment with human growth hormone.
Twenty patients with rheumatoid arthritis or Still's disease associated with growth failure were treated with human growth hormone, 7.5 to 17 U/m2 body surface per week. Five patients did not respond with better growth. In the remainder the mean growth rate increased from 1.9 cm/year (range: 0 to 3.3) to 6.2 cm/year (range: 3.6 to 12) over 5 to 7 months. Twelve patients treated for longer periods increased their mean growth rate from 2.6 cm/year (range: 0.7 to 5.7) to 6.3 cm/year (range: 2.4 to 9.7) and continued to grow during a second year of treatment. Growth velocity decreased in 6 patients when the hGH therapy was discontinued. The causes for this improvement in growth are possibly multifactorial: the growth rate is depressed by the severity of the disease and high-dose glucocorticoid therapy. Increases of growth rate occurred during improvements in the disease, reduction of steroid medication, as a result of therapy with human growth hormone, and because of puberty in some patients. Human growth hormone seemed to improve the underlying condition of four of the patients but had no influence on the disease in the remaining children.


Factors associated with serum CA125 level in women without ovarian cancer in the United States: a population-based study.
Cancer antigen 125 (CA125) is clinically used to monitor response to therapy in ovarian cancer and has been proposed for use in detecting ovarian cancer. This population-based study examines how demographic characteristics, gynecologic/reproductive history, chronic non-malignant medical conditions, history of non-ovarian cancer, lifestyle practices, and biomarkers of inflammation correlate with serum CA125 in both premenopausal and postmenopausal women without ovarian cancer across the United States. Participants were identified from the National Health and Nutrition Examination Survey 2001-2002. Linear and logistic regression models were applied. Higher CA125 levels were found to correlate with younger age, Non-Hispanic White race/ethnicity, and lower body mass index. In premenopausal women (N = 1157), current smoking was associated with lower CA125 (- 24.95%, p = 0.008), and history of non-ovarian cancer was associated with higher CA125 (40.64%, p = 0.045) by multivariable linear regression; both current smoking (odds ratio (OR) = 0.42, p = 0.043) and oral contraceptive pill (OCP) use of 5-10 years (OR = 0.31, p = 0.032) were less likely to be associated with having CA125 level ≥ 35 U/ml by multivariable logistic regression. In postmenopausal women (N = 1116), coronary artery disease (CAD) history was associated with higher CA125 (28.27%, p = 0.047) by multivariable linear regression; history of CAD (OR = 5.00, p = 0.011), history of breastfeeding (OR = 2.46, p = 0.026), and increased CRP level (OR = 1.41, p = 0.042) were more likely to be associated with having CA125 level ≥ 35 U/ml by multivariable logistic regression. Results suggest CA125 is lower in premenopausal women who are current smokers and OCP users of moderately longer duration but higher in those with non-ovarian cancer. CA125 is higher in those postmenopausal women with CAD, history of breastfeeding and elevated CRP level. These associations can inform clinical interpretation of individual patients' CA125 levels.


Author Correction: The copy number variation landscape of congenital anomalies of the kidney and urinary tract.
In the version of this article initially published, affiliation 38 incorrectly read "ICNU-Nephrology and Urology Department, Barcelona, Spain"; "Renal Division, Hospital Clinic, IDIBAPS, University of Barcelona, Barcelona, Spain" is the correct affiliation. The error has been corrected in the HTML and PDF versions of the article.


A randomised multicentre phase II study with cisplatin/docetaxel vs oxaliplatin/docetaxel as first-line therapy in patients with advanced or metastatic non-small cell lung cancer.
This study was designed to compare cisplatin/docetaxel with oxaliplatin/docetaxel in patients with advanced and metastatic non-small lung cancer as a first-line treatment. Patients were randomly assigned to receive either cisplatin 75 mg m(-2) and docetaxel 75 mg m(-2) every 3 weeks or oxaliplatin 85 mg m(-2) and docetaxel 50 mg m(-2) every 2 weeks. The primary end point was response rate, and secondary end points were toxicity, time to progression and overall survival. A total of 88 patients (median age: 65 (39-86) years; stage IV: 93%) were randomly assigned. Response rate (complete and partial response) was 47% (95% CI: 33-61%) in the cisplatin/docetaxel arm and 28% (95% CI: 17-43%) in the oxaliplatin/docetaxel arm (P=0.118). There was no significant difference in time to progression (6.3 vs 4.9 months, P=0.111) and median overall survival (11.6 vs 7.0 months, P=0.102) with cisplatin/docetaxel vs oxaliplatin/docetaxel, although slight trends favouring cisplatin were seen. Oxaliplatin/docetaxel was associated with significantly less (any grade) renal toxicity (56% vs 11%), any grade fatigue (81% vs 59%), complete alopecia (76% vs 27%), any grade leukopenia (84% vs 61%) and grade 3/4 leukopenia (44% vs 14%) and neutropenia (56% vs 27%). Oxaliplatin/docetaxel has activity in metastatic non-small cell lung cancer, but it seems to be inferior to cisplatin/docetaxel.


Fatty acid synthase and stearoyl-CoA desaturase-1 are conserved druggable cofactors of Old World Alphavirus genome replication.
Chikungunya virus (CHIKV) is a rapidly emerging mosquito-borne RNA virus that causes epidemics of debilitating disease in tropical and sub-tropical regions with autochtonous transmission in regions with temperate climate. Currently, there is no licensed vaccine or specific antiviral drug available against CHIKV infection. In this study, we examine the role, in the CHIKV viral cycle, of fatty acid synthase (FASN) and stearoyl-CoA desaturase (SCD1), two key lipogenic enzymes required for fatty acid production and early desaturation. We show that both enzymes and their upstream regulator PI3K are required for optimal CHIKV infection. We demonstrate that pharmacologic manipulation of FASN or SCD1 enzymatic activity by non-toxic concentrations of cerulenin or CAY10566 decreases CHIKV genome replication. Interestingly, a similar inhibitory effect was also obtained with Orlistat, an FDA-approved anti-obesity drug that targets FASN activity. These drugs were also effective against Mayaro virus (MAYV), an under-studied arthritogenic Old world Alphavirus endemic in South American countries with potential risk of emergence, urbanization and dispersion to other regions. Altogether, our results identify FASN and SCD1 as conserved druggable cofactors of Alphavirus genome replication and support the broad-spectrum activity of drugs targeting the host fatty acids metabolism.


The accuracy of the inferior>superior>nasal>temporal neuroretinal rim area rule for diagnosing glaucomatous optic disc damage.
To determine the accuracy with which the optic disc can be diagnosed as normal or glaucomatous according to the ISNT rule, whereby, in the normal eye, the neuroretinal rim area follows the order inferior (I) > superior (S) > nasal (N) > temporal (T). Prospective, cross-sectional, observational, case series. Fifty-one normal individuals and 78 individuals with open-angle glaucoma exhibiting field loss (median mean deviation, -4.37 dB; interquartile range [IQR], -2.10 to -7.96 dB; median pattern standard deviation, 5.65 dB; IQR, 2.94 to 8.56 dB). The reference diagnosis was made by 2 experts on the basis of the appearance of the optic disc and of the corresponding visual field. Stereoscopic optic disc photographs, acquired for each individual, were digitized at high resolution and analyzed using a digital, quad-buffered, stereoscopic viewing system in which a Z screen was used to dissociate the images to the 2 eyes of the observer. Three expert observers, trained to fellowship standard in glaucoma, independently undertook planimetry of the neuroretinal rim and of the disc margin from 1 eye of each individual, using a cursor moving in stereoscopic space to minimize parallax errors. Software automatically calculated the neuroretinal rim area in 10°, 30°, 40°, and 90° segments. For the ISNT rule to be obeyed, the 3 Boolean comparisons of the neuroretinal rim area, I>S, S>N, and N>T, had to be true. If any of the comparisons returned false, the rule was considered not to have been obeyed. Values were compared at a precision of 0.0001 mm(2). The outcome of the ISNT rule in terms of the 3 Boolean comparisons of the neuroretinal rim area was specified in terms of the sensitivity, specificity, and hence, the positive and negative likelihood ratios. Based on the ISNT rule being obeyed for 10° segments, the positive likelihood ratio among the 3 observers was 1.11 (95% confidence interval [CI], 0.99-1.25), 1.07 (95% CI, 0.94-1.21), and 1.06 (95% CI, 0.96-1.18), respectively. It was similar for the other segment sizes. Variants of the rule were not appreciably better. The ISNT rule has limited utility in the diagnosis of open-angle glaucoma.