Cortical correlation structure of aperiodic neuronal population activity.
Electrophysiological population signals contain oscillatory and non-oscillatory aperiodic (1/frequency-like) components. So far research has largely focused on oscillatory activity, and only recently, interest in aperiodic population activity has gained momentum. Accordingly, while the cortical correlation structure of oscillatory population activity has been characterized, little is known about the correlation of aperiodic neuronal activity. To address this, we investigated aperiodic neuronal population activity in the human brain using resting-state magnetoencephalography (MEG). We combined source-analysis, signal orthogonalization and irregular-resampling auto-spectral analysis (IRASA) to systematically characterize the cortical distribution and correlation of aperiodic neuronal activity. We found that aperiodic population activity is robustly correlated across the cortex and that this correlation is spatially well structured. Furthermore, we found that the cortical correlation structure of aperiodic activity is similar but distinct from the correlation structure of oscillatory neuronal activity. Anterior cortical regions showed the strongest differences between oscillatory and aperiodic correlation patterns. Our results suggest that correlations of aperiodic population activity serve as robust markers of cortical network interactions. Furthermore, our results show that aperiodic and oscillatory signal components provide non-redundant information about large-scale neuronal correlations. This may reflect at least partly distinct neuronal mechanisms underlying and reflected by oscillatory and aperiodic neuronal population activity.


Cellular cardiomyoplasty into infracted swine's hearts by retrograde infusion through the venous coronary sinus: An experimental study.
The aim was to create a model of myocardial infarction with a borderline myocardial impairment which would enable evaluation of the retrograde cellular cardiomyoplasty through the venous coronary sinus in a large animal model. Fifteen (study group) and 10 juvenile farm pigs (control group) underwent distal left anterior descending artery ligation. One month later the study group animals underwent sternotomy and a murine myoblastic line C2-C12 was injected at a constant pressure of 30mmHg, into the coronary sinus. Thirty days later all animals that survived from both groups underwent transthoracic echocardiography and 99Tc scintigraphy and were later euthanized and specimens were taken for microscopic evaluation. Cardiac output decreased significantly after ligation (p<0.001) and increased significantly after cardiomyoplasty (p<0.001). In all animals, the surgical induction of myocardial infarction caused a marked decline in the echocardiographic values of cardiac function; however, the cardiac function and dimensions were significantly improved in the study group after cardiomyoplasty versus the control group. All animals undergoing cardiomyoplasty demonstrated a significant reduction of the perfusion deficit in the left anterior descending artery territory, instead such data remained unchanged in the control group. The histological examination demonstrated the engrafted myoblasts could be distinguished from the activated fibroblasts in the scar tissue because they never showed any signs of collagen secretion and fiber buildup. In conclusion, the venous retrograde delivery route through the coronary sinus is safe and effective, providing a significant improvement in function and viability.


Treatment of Rat Lymphedema by Propeller Lymphatic Tissue Flap Combined with Nanofibrillar Collagen Scaffolds.
The aim of our study was to evaluate a new propeller vascularized lymphatic tissue flap (pVLNT) combined with aligned nanofibrillar collagen scaffolds (CS) (BioBridge) in reducing lymphedema in the rat lymphedema model. Unilateral left hindlimb lymphedema was created in 15 female Sprague-Dawley rats following inguinal and popliteal lymph nodes (LN) resection and radiation. An inguinal pVLNT was elevated from the contralateral groin and transferred through a skin tunnel to the affected groin. Four collagen threads were attached to the flap and inserted in the hindlimb at the subcutaneous level in a fan shape. The three study groups consisted of group A (control), group B (pVLNT), and group C (pVLNT + CS). Volumetric analysis of both hindlimbs was performed using micro-computed tomography imaging before the surgery (at initial time point) and then at 1 and 4 months, postoperatively, and the relative volume difference (excess volume) was measured for each animal. Lymphatic drainage was assessed by indocyanine green (ICG) fluoroscopy for number and morphology of new collectors and the time required for ICG to move from injection point to the midline. Four months after the induction of lymphedema, an increased relative volume difference remained in group A (5.32 ± 4.74%), while there was a significant relative volume reduction in group B (-13.39 ± 8.55%) and an even greater reduction in group C (-14.56 ± 5.04%). ICG fluoroscopy proved the functional restoration of lymphatic vessels and viability of pVLNT in both B and C groups. Notably, only group C demonstrated statistically significant improvements in lymphatic pattern/morphology and in the number of lymphatic collectors as compared with the control group A. The pedicle lymphatic tissue flap combined with SC is an effective procedure for the treatment of lymphedema in rats. It can be easily translated into treatment of humans' lower and upper limb lymphedema and further clinical studies are warranted.


Brain training in older adults: evidence of transfer to memory span performance and pseudo-Matthew effects.
In this study the effects of 'brain training' using the Nintendo DS Brain Training program were examined in two groups of older adults; the cognitive performance of an experimental group (n = 21) who were asked to use the Nintendo DS regularly over a 6-week period was compared with the control group (n = 20). Groups were matched on age (mean age = 74 years), education, computer experience, daily activities (time spent reading or watching television), and initial scores of Wechsler Adult Intelligence Scale. Analyses revealed that improvements were primarily in the Digit Span Test, specifically Digits Backwards. Although the Brain Training package appeared to have some efficacy, other factors such as perceived quality of life and perceived cognitive functioning were at least equally important in determining training outcomes. The implications of these findings for cognitive training are discussed.


Assessment of drug use pattern using WHO core drug use indicators in selected general hospitals: a cross-sectional study in Tigray region, Ethiopia.
Inappropriate use of medicine is a global challenge with greater impact on developing countries. Assessment of drug use pattern is used to identify gaps in medicine utilisation to implement strategies for promoting rational drug use. This study aimed to assess drug use pattern using the WHO drug use indicators in selected general hospitals in Tigray region, Ethiopia. A cross-sectional study was conducted using WHO drug use indicators in two public hospitals located in Tigray. Prescriptions recorded from 1 January 2017 to 1 June 2019 were randomly selected, and participants who visited the public hospitals from 1 March 2019 to 30 August 2019 and hospital pharmacies were interviewed. 100 patients who visited both outpatient clinics and hospital pharmacy departments of the public hospitals. The average number of medicines per prescription was 1.69 (±0.81). Prescriptions containing antibiotics and injectables were 58.2% and 15.9%, respectively. The percentages of medicines prescribed with a generic name from essential medicines list of Ethiopia were 97.5% (974) and 88.1% (970) in Mekelle Hospital and Quiha Hospital, respectively. The patients spent an average of 6.6(±3.5) min with their general practitioners, while only 22.8 (±21.7) s with their pharmacists. Of the patients interviewed, 56.9% knew their dosing regimen and 32.7% of them had their medication labelled. The finding of the present study revealed deviation of drug use pattern from the WHO optimal levels suggesting the hospitals had limitations in appropriate utilisation of medicines. Understanding the factors attributed to the observed gaps and implementing corrective measures are required to conform with the recommended standards of appropriate drug utilisation.


Deregulated Wnt/beta-catenin program in high-risk neuroblastomas without MYCN amplification.
Neuroblastoma (NB) is a frequently lethal tumor of childhood. MYCN amplification accounts for the aggressive phenotype in a subset while the majority have no consistently identified molecular aberration but frequently express MYC at high levels. We hypothesized that activated Wnt/beta-catenin (CTNNB1) signaling might account for this as MYC is a beta-catenin transcriptional target and multiple embryonal and neural crest malignancies have oncogenic alterations in this pathway. NB cell lines without MYCN amplification express higher levels of MYC and beta-catenin (with aberrant nuclear localization) than MYCN-amplified cell lines. Evidence for aberrant beta-catenin-TCF transcriptional activity was demonstrated using expression profiles from 73 primary NBs. Findings included increased WNT ligands (WNT1, WNT6, WNT7A, WNT10B), DVL1 and TCF7 expression in high-risk NBs without MYCN amplification, consistent with canonical beta-catenin signaling. More directly, Patterns of Gene Expression and Gene Set Enrichment Analyses demonstrated beta-catenin target genes (for example, MYC, PPARD, NRCAM, CD44, TCF7) as coordinately upregulated in high-risk NBs without MYCN amplification in comparison to high-risk MYCN-amplified or intermediate-risk NBs, supporting pathway activation in this subset. Thus, high-risk NBs without MYCN amplification may deregulate MYC and other oncogenic genes via altered beta-catenin signaling providing a potential candidate pathway for therapeutic inhibition.


Neuraminidase-mediated, NKp46-dependent immune-evasion mechanism of influenza viruses.
Natural killer (NK) cells play an essential role in the defense against influenza virus, one of the deadliest respiratory viruses known today. The NKp46 receptor, expressed by NK cells, is critical for controlling influenza infections, as influenza-virus-infected cells are eliminated through the recognition of the viral hemagglutinin (HA) protein by NKp46. Here, we describe an immune-evasion mechanism of influenza viruses that is mediated by the neuraminidase (NA) protein. By using various NA blockers, we show that NA removes sialic acid residues from NKp46 and that this leads to reduced recognition of HA. Furthermore, we provide in vivo and in vitro evidence for the existence of this NA-mediated, NKp46-dependent immune-evasion mechanism and demonstrate that NA inhibitors, which are commonly used for the treatment of influenza infections, are useful not only as blockers of virus budding but also as boosters of NKp46 recognition.


Oats-From Farm to Fork.
Oats have a long history of use as human food and animal feed. From its origins in the Fertile Crescent, the oat has adapted to a wide range of climatic conditions and geographic regions. Its unique macro-, micro-, and phytonutrient composition, high nutritional value, and relatively low agricultural input requirements makes oats unique among cereal crops. The health benefits of the oats are becoming well established. While the connection between oat β-glucan fiber in reducing the risk of cardiovascular disease and controlling glycemia have been unequivocally established, other potential benefits including modulation of intestinal microbiota and inflammation continue to be explored. Advances in food technology are continuing to expand the diversity of oat-based foods, creating opportunities to deliver the health benefits of oats to a larger segment of the population.


Introduction.
Innate immunity plays an important role in the host defense of a variety of different pathogens, and its responses must be tightly regulated to effectively eliminate microbial invasion and avoid immune-related diseases. Autophagy is a homeostatic process that is critical for the bulk degradation of cellular constituents. Recently, accumulating evidence demonstrates the emerging role of the autophagy in the regulation of innate immune responses. In this chapter, we will have a broad overview of the function of autophagy in innate immunity, and briefly introduce the composition of this book and the content of each chapter.


Running Injuries During Adolescence and Childhood.
The popularity of running among young athletes has significantly increased over the past few decades. As the number of children who participate in running increases, so do the potential number of injuries to this group. Proper care of these athletes includes a thorough understanding of the unique physiology of the skeletally immature athlete and common injuries in this age group. Treatment should focus on athlete education, modification of training schedule, and correction of biomechanical deficits contributing to injury. Early identification and correction of these factors will allow a safe return to running sports.


Impact of Cardiac Magnetic Resonance to Arrhythmic Risk Stratification in Nonischemic Cardiomyopathy.
Left ventricular ejection fraction-based arrhythmic risk stratification in nonischemic cardiomyopathy (NICM) is insufficient and has led to the failure of primary prevention implantable cardioverter defibrillator trials, mainly due to the inability of selecting patients at high risk for sudden cardiac death (SCD). Cardiac magnetic resonance offers unique opportunities for tissue characterization and has gained a central role in arrhythmic risk stratification in NICM. The presence of myocardial scar, denoted by late gadolinium enhancement, is a significant, independent, and strong predictor of ventricular arrhythmias and SCD with high negative predictive value. T1 maps and extracellular volume fraction, which are able to quantify diffuse fibrosis, hold promise as complementary tools but need confirmatory results from large studies.


Simulation-based education to promote confidence in managing clinical aggression at a paediatric hospital.
An increasing number of incidents involving aggressive behaviour in acute care hospitals are being witnessed worldwide. Acute care hospital staff are often not trained or confident in managing aggression. Competent management of clinical aggression is important to maintain staff and patient safety. Training programmes for acute care staff are infrequently described in the literature and rarely reported for paediatric staff. Simulation training allows practice of skills without patient risk and may be more effective than traditional teaching formats for aggression management. The aim of this proof of concept study was to develop a simulation-based education session on aggression management for acute care paediatric staff based on best practice principles, to evaluate the acceptability of this training programme and to gain an understanding of the impact of the training on participants' perceived confidence in managing clinical aggression. Two separate simulation exercises were delivered as a 2-h component of a hospital management of clinical aggression (MOCA) training day. Participants completed a written survey immediately prior to, at completion of the simulation-based group training, and at 3-6 months following the simulation training. Nine training days were conducted in 2017 for nursing, medical, allied health, education and security staff with a total of 146 participants (83% were acute care nurses). Two thirds (68%) of participants had experienced clinical aggression as part of their routine work, with 51% overall reporting a lack of confidence managing these patients. Immediately following the simulation training, 80% of all participants reported feeling more confident in managing clinical aggression, 47% reported a 1-point increase in confidence, whilst 33% of participants reported a 2- or 3-point increase. At 3-6 months post-training, 66% of respondents (N = 44) reported continued confidence in managing aggression with 100% of participants stating they would recommend simulation training to colleagues. Simulation training is an acceptable method of training and shows promise to improve staff-perceived confidence for managing behavioural emergencies in acute paediatric health care settings. In addition, there were potential enduring positive impacts at 3 months after the study. Whilst resource and time intensive, further research assessing the benefits of utilising simulation training in this setting is warranted in order to minimise staff burn-out and improve outcomes for these very vulnerable patients.


Contextual factors associated with sexual behavior among Brazilian adolescents.
There are few studies about the influence of the context on sexual behavior among adolescents in developing countries, such as Brazil. Adolescent pregnancy and the high incidence of sexually transmitted disease (STDs) among Brazilian youngsters are a public health problem. The object of this study was to investigate whether factors from family and school contexts are associated with sexual behavior among Brazilian adolescents. This study used data from 60,973 adolescent participants in the National Survey of School Health. The response variable was sexual behavior, described in three categories (never had sexual intercourse, had protected sexual intercourse, had unprotected sexual intercourse). The explanatory variables were grouped into sociodemographic characteristics, number of risk behavior factors (regular use of alcohol, smoking, and experimenting with illicit drugs), and family and school context. Variables associated with having protected and unprotected sexual relations in each context were identified by means of multinomial logistic regression. The reference was "never had sexual intercourse." Approximately one fourth of adolescents have already had sexual intercourse, most frequently boys. Among the adolescents who declared sexual initiation, the most part had their first sexual relation with age of 13 years or younger. Almost 21% did not use protection the last time they had sex. The greater the number of risk factors involved, the higher the incidence of protected and unprotected sex. In the family context, living with only one or with neither parent and low parental supervision increased the frequency of protected and unprotected sex. Never eating meals with the parents augmented the incidence of unprotected sex (odds ratio [OR], 1.60). In the school context, students from private schools were less likely to have had protected and unprotected sex (OR, 0.58 and 0.68). Not receiving instructions at school about pregnancy prevention increased the frequency of protected and unprotected sex (OR, 1.33 and 1.74, respectively). Family and school context factors are associated with sexual behavior. These associations are generally stronger for unprotected sex. Information about the prevention of pregnancy and STDs/AIDS has to be disseminated very early owing to the young age of sexual initiation.


Investigation of Salmonella Enteritidis outbreaks in South Africa using multi-locus variable-number tandem-repeats analysis, 2013-2015.
Salmonella enterica serovar Enteritidis (Salmonella Enteritidis) has become a significant pathogen in South Africa, and the need for improved molecular surveillance of this pathogen has become important. Over the years, multi-locus variable-number tandem-repeats analysis (MLVA) has become a valuable molecular subtyping technique for Salmonella, particularly for highly homogenic serotypes such as Salmonella Enteritidis. This study describes the use of MLVA in the molecular epidemiological investigation of outbreak isolates in South Africa. Between the years 2013 and 2015, the Centre for Enteric Diseases (CED) received 39 Salmonella Enteritidis isolates from seven foodborne illness outbreaks, which occurred in six provinces. MLVA was performed on all isolates. Three MLVA profiles (MLVA profiles 21, 22 and 28) were identified among the 39 isolates. MLVA profile 28 accounted for 77% (30/39) of the isolates. Isolates from a single outbreak were grouped into a single MLVA profile. A minimum spanning tree (MST) created from the MLVA data showed a close relationship between MLVA profiles 21, 22 and 28, with a single VNTR locus difference between them. MLVA has proven to be a reliable method for the molecular epidemiological investigation of Salmonella Enteritidis outbreaks in South Africa. These foodborne outbreaks emphasize the importance of the One Health approach as an essential component for combating the spread of zoonotic pathogens such as Salmonella Enteritidis.


[Effectiveness of using oxygen at different periods of increased atmospheric pressure action (experimental studies)].
The allowable value of nitrogen supersaturation was determined in 4 dogs during 219 experiments in a hyperbaric atmosphere (2 and 3 ata) which simulated diving. In the course of a 1-and 4-hour exposure of dogs to increased pressures of oxygen and an inert gas the allowable value may either decrease or increase. In order to increase the value, it is most effective and reliable to allow a 20-minute prebreathing of oxygen at 2--3 ata.


Financial Conflicts of Interest and Study Results in Environmental and Occupational Health Research.
To date, there is no comprehensive analysis of the relationship between financial conflict of interest (COI) and a potential publication bias in environmental and occupational health studies. We analyzed original research articles published in 2012 in 17 peer-reviewed journals. Multivariable ordinal logistic regression models were developed to evaluate the relationship between financial COI and the study outcome. Of the 373 studies included in the analysis, 17.2% had a financial COI associated with organizations involved with the processing, use, or disposal of industrial and commercial products, and studies with this type of COI were more likely to report negative results (Adjusted Odds Ratio = 4.31), as were studies with any COI associated with the military (employment or funding; Adjusted Odds Ratio = 9.15). Our findings show a clear relationship between direction of reported findings and specific types of financial COI.


On Rigid Minimal Spaces.
A compact space X is said to be minimal if there exists a map f : X → X such that the forward orbit of any point is dense in X. We consider rigid minimal spaces, motivated by recent results of Downarowicz, Snoha and Tywoniuk (J Dyn Differ Equ, 29:243-257, 2017) on spaces with cyclic group of homeomorphisms generated by a minimal homeomorphism, and results of the first author, Clark and Oprocha (Adv Math, 335:261-275, 2018) on spaces in which the square of every homeomorphism is a power of the same minimal homeomorphism. We show that the two classes do not coincide, which gives rise to a new class of spaces that admit minimal homeomorphisms, but no minimal maps. We modify the latter class of examples to show for the first time existence of minimal spaces with degenerate homeomorphism groups. Finally, we give a method of constructing decomposable compact and connected spaces with cyclic group of homeomorphisms, generated by a minimal homeomorphism, answering a question in Downarowicz et al.


Short-term and delayed behavioral effects of pre- and post-weaning morphine in mice.
Ninety mouse pups of the CD-1 outbred strain were used to assess activity (Varimex Activity Meter, Columbus Instr., OH) and analgesia (hot plate) after morphine hydrochloride given IP either on days 14-16 (preweanlings) or on days 21-23 (postweanlings). In preweanlings morphine depressed activity already at the lowest dose tested (0.5 mg/kg), and higher doses (1, 5, and 10 mg/kg) did not produce a significantly larger effect. Activity of postweanlings was not depressed until a very high dose (20 mg/kg). By contrast, morphine produced clear analgesic effects at all doses in both preweanlings (day 14) and postweanlings (day 21). Around day 70, activity and hot-plate tests in the no-drug state showed no differences due to prior treatment, except for the fact that hot-plate latencies of mice previously injected with saline as preweanlings were higher than those of all other groups. Twenty-four hr later the tests were repeated after morphine injection (10 mg/kg), and showed a significantly greater depression of activity in mice previously exposed as preweanlings. On the other hand, all groups previously exposed to morphine at either the pre- or the post-weanling stage showed tolerance to the analgesic effect of the drug. These developmental profiles confirm that opioid systems contribute to the modulation of activity by mechanisms which are at least in part separate from those mediating analgesia.


The molecular chaperone CCT modulates the activity of the actin filament severing and capping protein gelsolin in vitro.
The oligomeric molecular chaperone CCT is essential for the folding of the highly abundant protein actin, which in its native state forms actin filaments that generate the traction forces required for cell motility. In addition to folding proteins, CCT can provide a platform for protein complex assembly and binds actin filaments assembled in vitro. Some individual subunits of CCT, when monomeric, have been shown to be functionally active, and in particular, the CCTepsilon subunit is involved in the serum response factor pathway that controls actin transcription. Thus, there is a complex interplay between CCT and actin that extends beyond actin folding. CCT has recently been shown to bind gelsolin, an actin filament severing protein that increases actin dynamics by generating filament ends for further actin polymerization. However, the biological significance of the CCT:gelsolin interaction is unknown. Here, using a co-immunoprecipitation assay, we show that CCT binds directly to gelsolin in its calcium-activated, actin-severing conformation. Furthermore, using actin filaments retained from fixed and permeabilized cells, we demonstrate that CCT can inhibit the actin filament severing activity of gelsolin. As our work and that of others shows gelsolin is not folded by CCT, the CCT:gelsolin interaction represents a novel mode of binding where CCT may modulate protein activity. The data presented here reveal an additional level of interplay between CCT and actin mediated via gelsolin, suggesting that CCT may influence processes depending on gelsolin activity, such as cell motility.


[Intraocular pressure related to uveitis].
Glaucoma, a common and potentially devastating complication of intraocular inflammation, remains a considerable therapeutic challenge. During uveitis, breakdown of the blood-ocular barrier occurs with subsequent influx of proteins as well as inflammatory and immunocompetent cells. These mediators, including cytokines and chemokines, are considered to have a major impact on secondary elevated intraocular pressure (IOP). Several mechanisms are involved in the pathogenesis of inflammatory glaucoma, including obstruction of the trabecular meshwork by inflammatory cells and proteins, trabeculitis, formation of anterior and/or posterior synechiae, pupillary block, neovascularization, and anterior rotation of the lens-iris diaphragm. In addition, the use of steroids to control intraocular inflammation may cause secondary elevation of IOP.The management of uveitic glaucoma requires a careful balance between adequate anti-inflammatory therapy and appropriate lowering of IOP to prevent long-term visual loss. Despite the availability of many new medical treatments for both conditions, control of IOP in these patients remains challenging.


Postoperative bleeding. Current nursing management.
The critical care nurse caring for the postoperative bleeding patient must have a thorough knowledge of basic hemostatic principles and inherited and acquired disorders. Early recognition and treatment of bleeding problems reduces surgical morbidity and mortality; therefore astute clinical observations and a thorough understanding of selected laboratory testing are imperative. Because of the risk of disease transmission associated with homologous blood transfusion, new alternatives in blood therapy--autologous blood from preoperative and perioperative salvage; the conservative and individualized use of homologous blood and its components; blood substitutes to support oxygen transport (e.g., modified hemoglobin solutions and perfluorochemical emulsions); new pharmacologic approaches for minimizing blood loss (e.g., desmopressin); and increasing the body's ability to produce blood (e.g., recombinant erythropoietin)--must be considered and the patient response carefully assessed. A broad knowledge base and clinical expertise are requisite in meeting the critical needs of the postoperative bleeding patient in a climate of rapidly developing diagnostic and therapeutic alternatives.


Atmospheric wet deposition of trace metal elements: Monitoring and modelling.
Trace elements (TEs), a group of atmospheric pollutants, have attracted considerable attention from scientists and government administrators worldwide. The wet deposition fluxes of nineteen trace elements (NTE) were monitored at Wanqingsha, a coastal site in the Pearl River Delta, for three consecutive years (2016.9-2019.8). Significant seasonal differences in NTE between wet and dry seasons were observed. The fluxes of crustal elements (Ca, Na, Al, Mg, K, Fe, Zn and Ba) were significantly higher than those of anthropogenic elements, accounting for over 99 % of the total annual wet deposition of 19 elements. Analysis of PM2.5 and rainfall samples reveals that both the fraction of each TE in the PM2.5 (CQ) and the Apparent Scavengance Ratio for TE (ASR, defined as the concentration ratio in rain and PM2.5) follow lognormal distributions. The logCQ variation for each element is relatively small but shows substantial differences, with means ranging from -5.48 to -2.03, while the logASRs for all elements show similar means (varying from 5.86 to 7.64) and an extremely wide range of variation. The influences of meteorological factors on CQ and ASR were also investigated. A simple box model framework was constructed to reasonably simplify the TE removal process by precipitation. The corresponding regression analysis showed significant correlations between NTE and the precipitation rate, PM2.5 concentration, ASR, and CQ, with R2 ranging from 0.711 to 0.970. By substituting the effects of environmental factors on ASR and CQ into the above relationship, temporal variations in NTE can be predicted. The reliability of the model was demonstrated by comparing model simulations with observations over three years. For most elements, the models can predict the temporal variation of NTE quite accurately, and even for the worst predictions, such as Al, Mg, K, Co and Cd, where predictions exceed observations by only an order of magnitude.


Complete genome sequence of a blaNDM-5-producing Escherichia coli DC71 assigned as ST410-O8:H9 and recovered from a captive giant panda (Ailuropoda melanoleuca) in China.
In this study, we report the complete genome sequence of a multidrug-resistant Escherichia coli strain recovered from a fecal sample from a captive giant panda in China. Antimicrobial susceptibility testing was performed. Genomic DNA from E. coli DC71 was sequenced using a Nanopore PromethION sequencer instrument (Oxford Nanopore Technologies, UK) and MGI High-throughput Sequencing MGISEQ-2000 platforms. The clean reads were de novo assembled using SPAdes v3.11. The complete genome was annotated and analyzed using multilocus sequence typing, serotyping, plasmid replicons, fimH typing, chromosomal point mutations, acquired antimicrobial resistance, and virulence genes with web tools available at the Center for Genomic Epidemiology. The complete genome, 4 991 906 bp in length and comprising 4677 protein-coding sequences, was generated. In silico analysis revealed that E. coli DC71 belonged to the ST410-O8:H9 subclone. A carbapenem resistance gene, blaNDM-5, was located on the pDC71-2 plasmid, coproducing blaTEM-1. Many other resistance determinants encoded by chromosomes and pDC71-3 were found. The virulence related genes carried by chromosomes were mostly related to enterohemorrhagic E. coli (EHEC) O157:H7. To our knowledge, this is the first complete genome of an E. coli ST410-O8:H9 strain recovered from captive giant panda in China. This multidrug-resistant E. coli subclone may pose potential risks to human and animal health. The genome sequence will be helpful to understand the genomic structure, its diversity, and the molecular mechanism allowing bacteria to disseminate the resistance gene.


A second form of Sox11 homologue identified in the orange-spotted grouper Epinephelus coioides: analysis of sequence and mRNA expression patterns.
Sox genes, a family of genes related to the mammalian sex-determining region Y (SRY) gene, are found throughout the animal kingdom, and involved in diverse developmental processes including sex determination and neurogenesis. Previously, we have identified one sox11 homologue, sox11b, from the ovary of the orange-spotted grouper. In the present study, another sox11 homologue, sox11a, was cloned from the brain. The orange-spotted grouper Sox11a contained the signature features of mammalian SOX11 homologues except the Pro-Glu rich region, was clustered with Sox11a homologues of other teleosts in the phylogenetic tree, and shared higher homologies with Sox11 of other species than the duplicated copy Sox11b. Interestingly, significant conservation was observed in the 3'UTR of sox11a but not sox11b transcripts when compared with mammalian Sox11 homologues. The expression of sox11a mRNA was detected in a wide range of tissues, with higher abundances in the central nervous system. During embryogenesis and larval development, the expression of sox11a mRNA remained at considerably high levels at all stages examined, from newly fertilized eggs, through organogenesis, to the larvae 18days posthatching. Together, these results indicated that the orange-spotted grouper sox11a was evolutionarily more conserved than sox11b, and may play important roles in neurogenesis, embryogenesis, and larval development.


A Systematic Approach to Treating Early Metabolic Disease and Prediabetes.
At least 70% of US adults have metabolic disease. However, less is done to address early disease (e.g., overweight, obesity, prediabetes) versus advanced disease (e.g., type 2 diabetes mellitus, coronary artery disease). Given the burden of advanced metabolic disease and the burgeoning pandemics of obesity and prediabetes a systematic response is required. To accomplish this, we offer several recommendations: (A) Patients with overweight, obesity, and/or prediabetes must be consistently diagnosed with these conditions in medical records to enable population health initiatives. (B) Patients with early metabolic disease should be offered in-person or virtual lifestyle interventions commensurate with the findings of the Diabetes Prevention Program. (C) Patients unable to participate in or otherwise failing lifestyle intervention must be screened to assess if they require pharmacotherapy. (D) Patients not indicated for, refusing, or failing pharmacotherapy must be screened to assess if they need bariatric surgery. (E) Regardless of treatment approach or lack of treatment, patients must be consistently screened for the progression of early metabolic disease to advanced disease to enable early control. Progression of metabolic disease from an overweight yet otherwise healthy person includes the development of prediabetes, obesity ± prediabetes, dyslipidemia, hypertension, type 2 diabetes, chronic kidney disease, coronary artery disease, and heart failure. Systematic approaches in health systems must be deployed with clear protocols and supported by streamlined technologies to manage their population's metabolic health from early through advanced metabolic disease. Additional research is needed to identify and validate optimal system-level interventions. Future research needs to identify strategies to roll out systematic interventions for the treatment of early metabolic disease and to improve the metabolic health among the progressively younger patients being impacted by obesity and diabetes.


Shortlist revealed for Patient's Choice category.
Voting is now open for the Patient's Choice category of the RCNi Nurse Awards 2017.


Human umbilical cord blood cells alter blood and spleen cell populations after stroke.
The human umbilical cord blood (HUCB) mononuclear cell (MNC) fraction is a mixed population of cells that induces functional repair in rodent models of stroke when injected intravenously (i.v.). The transplanted cells are found in the infarcted hemisphere and the spleen. The goal of this project was to determine the nature of the interaction between the HUCB MNCs cells and splenic immune cells. Male Sprague Dawley rats underwent permanent middle cerebral artery occlusion (MCAO) and received i.v. injection of either vehicle (MCAO only), HUCB MNCs or MNCs depleted of CD14+ monocytes, CD133+ stem cells or CD19+ B cells 48 hours post-stroke. At 72 hours post-MCAO, the animals were euthanized and the spleens and blood MNCs harvested for flow cytometry and mitogen proliferation assays. All HUCB cell preparations decreased the percentage of T cells in the spleen and monocytes in the blood (p < 0.05). MNCs depleted of CD14+ and CD19+ decreased the percentage of macrophage (p < 0.001), while CD133 depleted MNCs increased the percentage of macrophage in spleen (p < 0.001); MNC did not alter the macrophage population from the level observed after MCAO. Only HUCB MNC significantly decreased Concanavalin A (ConA)-induced T cell stimulation (p < 0.05). These results suggest that the effects of HUCB MNC in the spleen are not due to a single HUCB population, but the interaction of all the subpopulations together.


Myeloperoxidase activity and the oxidized proteins in blood neutrophils of patients with pneumonia.
The main purpose of our investigation was to study myeloperoxidase activity and concentration of oxidized proteins in blood neutrophils of patients with ambulant pneumonia and secondary pneumonia which has arisen on a background of chronic obstructive pulmonary disease (COPD). Patients were divided into 2 groups. 17 patients with ambulant pneumonia moderate severity and respiratory insufficiency of grade 2 were included in the 1-st group. 20 COPD patients with secondary pneumonia moderate severity and with respiratory insufficiency of grade 2 were included in the 2-nd group. The control group consisted of 15 healthy subjects. The reactive protein carbonyl derivates, advanced oxidation protein products (AOPP) and myeloperoxidase activity were detected in neutrophils. In neutrophils of 1-st group patients the augmentation of reactive protein carbonyl derivates was observed in comparison with healthy ones. In neutrophils of 2-nd group patients the slight decrease of reactive protein carbonyl derivates was observed in comparison with healthy ones (by 17%). In neutrophils of 2-nd group patients the significant increasing AOPP in comparison with healthy ones (p <0.01) and 1 group patients (p <0.05) was fixed. Myeloperoxidase activity was higher in neutrophils of 1-th group patients in comparison with healthy ones. In neutrophils of 2-nd group patients myeloperoxidase activity was higher in comparison with the same of 1 group patients (by 67%, p <0.05). Our results showed the different direction of oxidized proteins formation neutrophils of patients with primary and secondary pneumonia. Besides that the varied degree of myeloperoxidase activity was fixed. Our results require more detailed understanding because they can reflect peculiar mechanisms of pneumonia development and determine the characteristics of their progression.


Improved standardization in reversed-phase high-performance liquid chromatography using 1-nitroalkanes as a retention index scale.
A retention index scale based on 1-nitroalkanes was introduced for reversed-phase high-performance liquid chromatography. The retention behaviour of nitroalkanes was examined using two different ODS-silica columns. The nitroalkanes are stable compounds having high UV absorbances at 200-220 nm. The correlation between the logarithm of the capacity factor and the carbon number was linear from the second homologue. The compounds up to 1-nitrohexane are easily available commercially, and they cover the retention range for the majority of toxicologically relevant substances. The retention indices of several test compounds showed that the scale based on 1-nitroalkanes is comparable to that based on alkyl aryl ketones, and additionally may cover the early eluted compounds, for which reference compounds on the alkyl aryl ketone scale are not available.


Influence of temperature on the immune response of juvenile summer flounder, Paralichthys dentatus, and its role in the elimination of Trypanoplasma bullocki infections.
Two groups of juvenile summer flounder maintained at 5 degrees C were experimentally infected with the hemoflagellate Trypanoplasma bullocki. Another group maintained at 5 degrees C was not infected. The water temperature of one infected group was raised stepwise to 12 degrees C, 18 degrees C, and 24 degrees C for 2 to 3 weeks at each level. The other infected group was maintained at 5 degrees C for 12 weeks, the duration of the experiment. In addition, juvenile flounder were collected over a temperature range of 6 degrees C to 22 degrees C from February to June, 1982, to monitor natural infections. Live T. bullocki were incubated in plasma from fish at each temperature to monitor the host's humoral response. Trypanoplasmacidal lysis occurred in experimental infections maintained at 24 degrees C and in natural infections over a range experimental infections at 24 degrees C and in natural infections at 22 degrees C. Differences in temperature where lytic activity occurred was mainly attributable to the short time exposure of experimental infections to increasing temperatures in contrast to that occurring in nature. Trypanoplasmacidal lysis with increasing water temperatures in flounder indicates that the fish's humoral immunity is responsible for the annual spring decline in prevalence and eventual elimination of T. bullocki infections.


Dynamics of oxygen evolution and biomass production during cultivation of Agardhiella subulata microplantlets in a bubble-column photobioreactor under medium perfusion.
Cell and tissue cultures derived from macrophytic marine red algae are potential platforms for unique secondary metabolites. This work presents the first successful bioreactor cultivation study of an in vitro tissue culture derived from a macrophytic marine red alga. Specifically, the photosynthetic growth characteristics of a novel microplantlet suspension culture established from the macrophytic marine red alga Agardhiella subulata were studied. A bubble-column bioreactor with external illumination (43 microE m(-2) s(-1), 10:14 LD photoperiod), liquid medium perfusion, and 3800 ppm CO(2) in the aeration gas provided sufficient light and nutrient delivery for sustained growth of the microplantlet suspension at 24 degrees C and pH 8. Microplantlets, which consisted of shoot tissues of 3-5 mm length branching out from a common center, were not friable in a bubble-aerated suspension of about 1100 plantlets per liter. Since the microplantlet tissues were not friable, only batch and fed-batch cultivation modes were considered. Batch cultivation was phosphate-limited in ASP12 artificial seawater medium. However, cultivation at a medium perfusion rate of 20% per day avoided phosphate limitation and extended the growth phase to provide plantlet mass densities exceeding 14 g FW L(-1) (3.7 g DW L(-1)) after 50 days of cultivation if the suspension was not sampled. The specific oxygen evolution rate vs cultivation time profile possessed a significant pulse within the 14 days following inoculation and then leveled off at longer times. In recognition of this nonexponential growth pattern, a new photobioreactor growth model was developed that used the oxygen evolution rate vs time profile to predict the biomass growth curve in perfusion culture. Model predictions agreed reasonably with the measured growth curves.


Cutaneous manifestation during COVID-19 pandemic.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, causing COVID-19, is rapidly spread across the world, by posing novel challenges for all physicians. Cutaneous manifestations of COVID-19 may be present in 20% of patients, but they are still now poorly characterized. We search literature to describe all the various cutaneous manifestation observed during COVID-19 pandemic. Different cutaneous clinical patterns were described, showing a wide polymorphism. We provided an overview of all the various cutaneous manifestations of COVID-19 described in the literature today, to improve our knowledge and lead a more prompt and accurate diagnosis, especially in asymptomatic or paucisymptomatic cases.


Identification of Glossina palpalis gambiensis specific salivary antigens: towards the development of a serologic biomarker of human exposure to tsetse flies in West Africa.
The saliva of blood sucking arthropods contains a number of pharmacologically active compounds that induce an antibody response in exposed human individuals. The objectives of the present study were (i) to assess the human IgG response directed against salivary antigens of Glossina palpalis gambiensis, the main vector of Trypanosoma brucei gambiense in West Africa, as a biomarker of human-tsetse contacts; and (ii) to identify specific salivary antigens. Immune reactivity of human plasma collected within active human African trypanosomiasis (HAT) foci (coastal Guinea), historical foci where tsetse flies are still present (South-West Burkina Faso) and a tsetse free area (Bobo-Dioulasso, Burkina Faso), was measured by ELISA against whole saliva extracts. In the active HAT foci and areas where tsetse flies were present in high densities, specific IgG responses were significantly higher (p < 0.0001) to those in Bobo-Dioulasso or in Loropeni, where tsetse flies were either absent or only present at low densities. Furthermore, 2D-electrophoresis combined with mass spectrometry enabled to reveal that several antigens were specifically recognized by plasma from exposed individuals. Among them, four salivary proteins were successfully identified (Ada, 5'Nuc, Ag5 and Tsgf1). These results represent a first attempt to identify Glossina salivary proteins or synthetic peptides to develop a standardized and specific biomarker of tsetse exposure in West Africa.


Postoperative Outcome of Surgery with Pancreatic Resection for Retroperitoneal Soft Tissue Sarcoma: Results of a Retrospective Bicentric Analysis on 50 Consecutive Patients.
Multivisceral resection is the standard treatment for retroperitoneal sarcoma (RPS) during which pancreas resection may be necessary. All consecutive patients operated for RPS with pancreatectomy in 2 expert centers between 1993 and 2018 were retrospectively analyzed. Fifty patients (median age: 57 years, IQR: [46-65]) with a primary (n = 33) or recurrent (n = 17) RPS underwent surgery requiring pancreas resection (distal pancreatectomy (DP) (n = 43), pancreaticoduodenectomy (PD) (n = 5), central pancreatectomy (n = 1), and atypical resection (n = 1)). Severe postoperative morbidity (Clavien-Dindo III-IV) was observed in 14 patients (28%), and 7 of them (14%) required reoperation for anastomotic bowel leakage (n = 5), gastric volvulus (n = 1), or hemorrhage (n = 1). Pancreas-related complications occurred in 25 patients (50%): 10 postoperative pancreatic fistulas (POPF) (grade A (n = 12), grade B (n = 6), grade C (n = 1)), 13 delayed gastric emptying (grade A (n = 8), grade B (n = 4), grade C (n = 1)), 1 hemorrhage (grade C). Postoperative mortality was 4% (n = 2), all following PD, caused by a massive intraoperative air embolism and by a multiple organ failure after anastomotic leakage. Pathological analysis confirmed pancreatic involvement in 17 (34%) specimens. Microscopically complete resection (R0) was achieved in 22 (44%) patients. After a follow-up of 60 months, 36 patients (75%) were still alive, among whom 27 without recurrence (56%). Pancreatic resection during RPS surgery is associated with significant postoperative morbidity and mortality. PD should be avoided whenever possible while other procedures seemed achievable without excessive morbidity and with long-term survival.


Phytochemical profile, antioxidant, α-amylase inhibition, binding interaction and docking studies of Justicia carnea bioactive compounds with α-amylase.
The present study investigated the antioxidant and invitro antidiabetic capacities of Justicia carnea aqueous leaf extract (JCAE) using α-amylase inhibition model. α-Amylase binding-interaction with JCAE was also investigated using fluorescence spectroscopy and molecular docking. Phytochemical screening and Gas Chromatography-Mass Spectrometry (GC-MS) analysis indicated presence of bioactive compounds. Phenolic (132 mg GAE/g) and flavonoid contents (31.08 mg CE/g) were high. JCAE exhibited high antioxidant capacity and effectively inhibited α-amylase activity (IC50, 671.43 ± 1.88 μg/mL), though lesser than acarbose effect (IC50, 108.91 ± 0.61 μg/mL). α-Amylase intrinsic fluorescence was quenched in the presence of JCAE. Ultraviolet-visible and FT-IR spectroscopies affirmed mild changes in α-amylase conformation. Synchronous fluorescence analysis indicated alterations in the microenvironments of tryptophan residues near α-amylase active site. Molecular docking affirmed non-polar interactions of compounds 6 and 7 in JCAE with Asp-197 and Trp-58 residues of α-amylase, respectively. Overall, JCAE indicated potential to prevent postprandial hyperglycemia by slowing down carbohydrate hydrolysis.


Further investigation of the epitope recognized by the new monoclonal antibody 2C9.
We established a new monoclonal antibody (2C9) that reacted with prostate tissue. The immunohistochemical reactivity of this antibody is similar to anti-prostate-specific membrane antigen (PSMA). Herein, we report the antigenic determinant of 2C9 antibody. The reactivity of the antibody was characterized by immunohistochemical staining and the antigen target was characterized by amino acid sequencing after immuno-affinity purification from an LNCaP cell lysate and cloning of a cDNA using a mammalian expression cDNA cloning system. The amino acid and nucleotide sequences for the antigen molecule recognized with 2C9 monoclonal antibody demonstrated identity with PSMA. The target molecule of the 2C9 monoclonal antibody is PSMA, pointing to future diagnostic and therapeutic applications.


Functional and expression characteristics identification of Phormicins, novel AMPs from Musca domestica with anti-MRSA biofilm activity, in response to different stimuli.
Antibiotic-resistant bacteria (including MRSA) in the clinic pose a growing threat to public health, and antimicrobial peptides (AMPs) have great potential as efficient treatment alternatives. Houseflies have evolved over long periods in complex, dirty environments, developing a special immune system to overcome challenges in harmful environments. AMPs are key innate immune molecules. Herein, two differentially expressed AMPs, Phormicins A and B, were identified by screening transcriptomic changes in response to microbial stimulation. Structural mimic assays indicated that these AMPs exhibited functional divergence due to their C-terminal features. Expression analysis showed that they had different expression patterns. Phormicin B had higher constitutive expression than Phormicin A. However, Phormicin B was sharply downregulated, whereas Phormicin A was highly upregulated, after microbial stimulation. The MIC, MBC and time-growth curves showed the antibacterial spectrum of these peptides. Crystal violet staining and SEM showed that Phormicin D inhibited MRSA biofilm formation. TEM suggested that Phormicin D disrupted the MRSA cell membrane. Furthermore, Phormicin D inhibited biofilm formation by downregulating the expression of biofilm-related genes, including altE and embp. Therefore, housefly Phormicins were functionally characterized as having differential expression patterns and antibacterial & antibiofilm activities. This study provides a new potential peptide for clinical MRSA therapy.


Fusiform aneurysm of the posterior cerebral artery: report of two cases.
Two cases with fusiform aneurysm in the posterior cerebral artery are presented: The first one is a large fusiform aneurysm of the P(2) segment of posterior cerebral artery (PCA) in a 58 years old patient and the second a fusiform aneurysm of the P(3) segment of PCA in a 43 years old patient. The aneurysms were successfully treated the first by proximal ligation and the second by trapping of the aneurysm. The patients had no additional neurological deficits postoperatively and they are in an good condition, in four years and one year follow up respectively. The operative approaches and the radiological investigation in relation to the micro-anatomy of the posterior cerebral artery, as well as the outcome in these cases are discussed.


Role of advanced glycation endproducts and potential therapeutic interventions in dialysis patients.
It has been nearly 100 years since the first published report of advanced glycation end products (AGEs) by the French chemist Maillard. Since then, our understanding of AGEs in diseased states has dramatically changed. Especially in the last 25 years, AGEs have been implicated in complications related to aging, neurodegenerative diseases, diabetes, and chronic kidney disease. Although AGE formation has been well characterized by both in vitro and in vivo studies, few prospective human studies exist demonstrating the role of AGEs in patients on chronic renal replacement therapy. As the prevalence of end-stage renal disease (ESRD) in the United States rises, it is essential to identify therapeutic strategies that either delay progression to ESRD or improve morbidity and mortality in this population. This article reviews the role of AGEs, especially those of dietary origin, in ESRD patients as well as potential therapeutic anti-AGE strategies in this population.


Integrin-mediated regulation of TGFβ in fibrosis.
Fibrosis is a major cause of morbidity and mortality worldwide. Currently, therapeutic options for tissue fibrosis are severely limited, and organ transplantation is the only effective treatment for end-stage fibrotic disease. However, demand for donor organs greatly outstrips supply, and so effective anti-fibrotic treatments are urgently required. In recent years, the integrin family of cell adhesion receptors has gained prominence as key regulators of chronic inflammation and fibrosis. Fibrosis models in multiple organs have demonstrated that integrins have profound effects on the fibrotic process. There is now abundant in vivo data demonstrating critical regulatory roles for integrins expressed on different cell types during tissue fibrogenesis. In this review, we will examine the ways in which integrins regulate these processes and discuss how the manipulation of integrins using function blocking antibodies and small molecule inhibitors may have clinical utility in the treatment of patients with a broad range of fibrotic diseases. This article is part of a Special Issue entitled: Fibrosis: Translation of basic research to human disease.


Relationship between vitamin D, iron, and hepcidin in premenopausal females, potentially confounded by ethnicity.
To investigate the associations between vitamin D, hepcidin, and iron status in premenopausal females of different ethnic cohorts residing in Auckland, New Zealand (NZ). A total of 160 females aged 18-45 years participated in a cross-sectional study. Demographics, body composition, serum 25(OH)D, inflammatory markers (C-reactive protein and interleukin-6, IL-6), and iron biomarkers (serum ferritin, haemoglobin, soluble transferrin receptor, and hepcidin) were measured. Comparisons between parametric, non-parametric, and categorical variables were completed by using one-way ANOVA, Kruskal-Wallis, and Chi-squared tests, respectively. ANCOVA was used to compare serum 25(OH)D across iron parameter categories. Of the 160 participants, 60 were NZ European, 67 were South Asian, and 33 were from the 'other' ethnic groups. South Asians had significantly higher body fat percentage (BF%) and IL-6 concentration (38.34% and 1.66 pg·mL-1, respectively), compared to NZ Europeans (27.49% and 0.63 pg·mL-1, respectively, p < 0.001). South Asians had significantly lower 25(OH)D concentrations compared to NZ Europeans (33.59 nmol·L-1 vs 74.84 nmol·L-1, p < 0.001). In NZ Europeans, higher 25(OH)D concentration was seen in those with lower (≤ 3.5 nM) hepcidin concentration, p = 0.0046. In South Asians, higher 25(OH)D concentration was seen in those with higher (> 3.5 nM) hepcidin concentrations, p = 0.038. There were no associations between serum 25(OH)D and serum ferritin. Within South Asian women, an unexpected positive relationship between 25(OH)D and hepcidin concentration was observed which may be due to significantly higher IL-6 concentrations, BF%, and lower 25(OH)D concentrations. Future research is required to confirm these observations in this ethnic cohort.


The fear hypothesis and tonic immobility (TI) modulation: Early studies in chickens.
The hypothesis that fear is involved in the mechanisms of tonic immobility (TI) has been supported by early studies conducted in newborn and adult chickens. The susceptibility to TI changes during development in parallel to other fear responses. TI duration increases following exposure before induction to threatening stimuli such as electric shock, loud sound, stuffed sparrow hawk, as well as in unfamiliar conditions applied before and/or during testing. TI duration and susceptibility are increased by prey/predator eye contact and inversely related with the predator distance. TI duration increases following exposure before induction to threatening stimuli such as electric shock, loud sound, stuffed sparrow hawk, as well as in unfamiliar conditions applied before and/or during testing. The fact that the experimenter presence or the experimenter eye visibility represent a potential source of fear like a natural predator in chicks and in adult hens is controversial. The likely explanations for the contradictory results are discussed in the text. The rearing conditions, for instance, seem to be critical: repeated handling in the first days after hatching reduces the fear of human beings, decreasing TI duration in adulthood with a parallel increase in proximity scores to the experimenter. In chicks, exposure to withdrawal from a positive imprinting stimulus increases and decreases TI duration, respectively.


Clinical Perspective of Carotid Plaque Imaging.
At present, patients with carotid disease are selected for invasive recanalization therapies mainly based on the degree of luminal narrowing and the presence or absence of recent ischemic symptoms. A more sophisticated risk model takes into account other clinical variables, such as age, sex, and the type of recent symptoms, as well as presence of ulcerated plaque. A growing body of evidence shows that noninvasive imaging of the carotid plaque by various methods reliably identifies structural correlates of plaque vulnerability, which are associated with an increased risk of cerebrovascular events.


Associational effects of plant defences in relation to within- and between-patch food choice by a mammalian herbivore: neighbour contrast susceptibility and defence.
A basic idea of plant defences is that a plant should gain protection from its own defence. In addition, there is evidence that defence traits of the neighbouring plants can influence the degree of protection of an individual plant. These associational effects depend in part on the spatial scale of herbivore selectivity. A strong between-patch selectivity together with a weak within-patch selectivity leads to a situation where a palatable plant could avoid being grazed by growing in a patch with unpalatable plants, which is referred to as associational defence. Quite different associational effects will come about if the herbivore instead is unselective between patches and selective within a patch. We studied these effects in a manipulative experiment where we followed the food choice of fallow deer when they encountered two patches of overall different quality. One of the two patches consisted of pellets with low-tannin concentration in seven out of eight buckets and with high concentration in the remaining bucket. The other patch instead had seven high- and one low-tannin bucket. We performed the experiment both with individuals one at a time and with a group of 16-17 deer. We found that the deer were unselective between patches, but selective within a patch, and that the single low-tannin bucket among seven high-tannin buckets was used more than a low-tannin bucket among other low-tannin buckets. This corresponds to a situation where a palatable plant that grows among unpalatable plants is attacked more than if it was growing among its own kind, and for this effect we suggest the term neighbour contrast susceptibility, which is the opposite of associational defence. We also found that the high-tannin bucket in the less defended patch was less used than the high-tannin buckets in the other patch, which corresponds to neighbour contrast defence. The neighbour contrast susceptibility was present both for individual and group foraging, but the strength of the effect was somewhat weaker for groups due to weaker within-patch selectivity.


In Vitro Antimicrobial Activity of Essential Oils from Sardinian Flora against Cutibacterium (Formerly Propionibacterium) acnes and Its Enhancement by Chitosan.
The in vitro antibacterial activity of some essential oils from Sardinian flora, both alone and in combination with chitosan, was investigated against a strain of Cutibacterium acnes, a bacterium involved in pathogenesis of acne. The composition of the essential oils was determined by gas chromatography and gas chromatography/mass spectrometry. The results of this investigation demonstrated that some of the oils examined, characterised by different chemical profiles, possessed some activity against C. acnes. Interestingly, this antibacterial effect was enhanced by sub-inhibitory concentrations of chitosan. These observations suggest the potential application of this synergy in the development of innovative topical formulations useful in the management of acne.


The effect of dragon-kings on the estimation of scaling law parameters.
Scaling laws are used to model how different quantifiable properties of cities, such as the number of road traffic accidents or average house prices, vary as a function of city population size, with parameters estimated from data. Arcaute et al. raised the issue of whether specific cities with extremely large population sizes, known as dragon-kings, should be considered separately from other smaller cities when estimating the scaling law parameters since the two types of cities tend to display different behaviour. Through the analysis of randomly generated samples, we find that the inclusion of dragon-kings in the scaling analysis does not affect the estimated values for the parameters but only provided that all the data points satisfy the same scaling law. We also analyse randomly generated samples where data corresponding to a particular city deviates from the scaling law followed by the rest of the cities. We then show that deviations corresponding to dragon-king cities have the most significant effect on the estimated values of the scaling parameters. The extent of this effect also depends on which estimation procedure is used. Our results have important implications on the suitability of scaling laws as a model for urban systems.


The effect of fetal hypothalamus grafts on weight gain resulting from lesions of the ventromedial hypothalamus.
Bilateral ventromedial hypothalamic lesions in female adult rats which resulted in hyperphagia and rapid weight gain were followed by placement of fetal brain tissue in the anterior third ventricle. The treatment group received fetal hypothalamus grafts, and fetal cortical tissue of identical age was grafted into the control group. A significant reduction in average daily weight gain was noted from 4 to 12 weeks following transplantation in the treatment group. At 12 weeks posttransplantation, the animals were sacrificed for histological analysis. Examination of the hypothalamus grafts revealed neurons, ependymal clusters, and axonal processes which appeared to infiltrate the surrounding hypothalamic parenchyma.


WiiFit™ Plus balance test scores for the assessment of balance and mobility in older adults.
The Nintendo Wii™ is becoming an increasingly popular technology for the training and assessment of balance in older adults. Recent studies have shown promising results for its use in fall prevention. However, it is not clear how scores on the WiiFit™ balance games relate to current standardized tests of balance and mobility. The purpose of this study was to evaluate the relationship between WiiFit™ Plus balance tests, and standardized tests of older adult fitness, balance, mobility, self-reported balance confidence, and visual attention and processing. Results from 34 older adult participants indicate that WiiFit™ balance tests do not correlate well with standardized functional balance, mobility and fitness tests. However, the Wii balance score, as measured by the Basic Balance Test of the WiiFit™, does correlate with visual processing speed as measured by the Useful Field of View (UFOV(®)) test. These results indicate that WiiFit™ balance tests may provide advantageous information supplementary to information obtained through standard functional mobility and balance tests; however, caution should be used when using the WiiFit™ balance tests in isolation. Further research is necessary as these technologies become widely used in clinical and home settings for balance training and assessment.


Increased plasma calcitonin levels in young spontaneously hypertensive rats: role in disturbed phosphate homeostasis.
In young spontaneously hypertensive rats (SHR) and in normotensive Wistar-Kyoto controls (WKY) several parameters of phosphate and calcium homeostasis were determined. At 6 and 8 weeks, blood analysis revealed a significant hypophosphatemia (p less than 0.001) in SHR and twice as high plasma calcitonin levels in SHR than in WKY controls. At 8 weeks, 1,25-dihydroxycholecalciferol concentration was 20% higher in SHR (p less than 0.02) while 25-hydroxycholecalciferol was unaltered (p greater than 0.51). In addition total immunoreactive PTH, iPTH, was slightly increased (p less than 0.07) but intact PTH (1-84) (p greater than 0.90) was not significantly different from age matched WKY controls. Also at 8 weeks, a slightly reduced serum ionized Ca2+ concentration (p less than 0.001) with no change in total serum calcium was found in SHR (p greater than 0.39). Balance studies at 6 and 8 weeks of age revealed no significantly different balances for phosphate (F = 2.5, p greater than 0.10) and for calcium (F = 2.6, p greater than 0.09), although a tendency for slightly more positive balances existed in SHR when compared to WKY. However, SHR excreted significantly less phosphate in the urine than WKY control (F = 0.2, p less than 0.0009). Bone analysis was performed on femora of SHR and WKY of 6 weeks of age. Femora were significantly shorter in SHR (20.54 +/- 0.35 vs. 21.50 +/- 0.05 mm in WKY), whereas bone dry weight (127 +/- 6 vs. 107 +/- 2 mg).(ABSTRACT TRUNCATED AT 250 WORDS)


Estimations of historical atmospheric mercury concentrations from mercury refining and present-day soil concentrations of total mercury in Huancavelica, Peru.
Detailed Spanish records of cinnabar mining and mercury production during the colonial period in Huancavelica, Peru were examined to estimate historical health risks to the community from exposure to elemental mercury (Hg) vapor resulting from cinnabar refining operations. Between 1564 and 1810, nearly 17,000 metric tons of Hg were released to the atmosphere in Huancavelica from Hg production. AERMOD was used with estimated emissions and source characteristics to approximate historic atmospheric concentrations of mercury vapor. Modeled 1-hour and long-term concentrations were compared with present-day inhalation reference values for elemental Hg. Estimated 1-hour maximum concentrations for the entire community exceeded present-day occupational inhalation reference values, while some areas closest to the smelters exceeded present-day emergency response guideline levels. Estimated long-term maximum concentrations for the entire community exceeded the EPA Reference Concentration (RfC) by a factor of 30 to 100, with areas closest to the smelters exceeding the RfC by a factor of 300 to 1000. Based on the estimated historical concentrations of Hg vapor in the community, the study also measured the extent of present-day contamination throughout the community through soil sampling and analysis. Total Hg in soils sampled from 20 locations ranged from 1.75 to 698 mg/kg and three adobe brick samples ranging from 47.4 to 284 mg/kg, consistent with other sites of mercury mining and use. The results of the soil sampling indicate that the present-day population of Huancavelica is exposed to levels of mercury from legacy contamination which is currently among the highest worldwide, consequently placing them at potential risk of adverse health outcomes.


Improvements in psychologists' metacommunication self-efficacy, willingness, and skill following online training and a supervision exercise.
Psychologists' experiences of an online training tool in metacommunication as well as an in-supervisory metacommunication exercise were examined. A total of 101 participants completed a training tool in metacommunication and changes in self-efficacy (SE) to use metacommunication with clients, the proportion of metacommunication used in vignette-responses, and their willingness to use metacommunication in supervision were assessed pre- and posttraining and at 6-week follow-up. A total of 48 participants elected to undertake the in-supervision exercise. Participants reported significantly higher willingness and self-efficacy after completing the online training. They also showed a higher proportion of metacommunicative statements in their posttraining vignette responses compared with pretraining. The increase in willingness was retained at 6-week follow-up. There was an increase in self-efficacy from pre- to postonline-training, and this increased at follow-up. This opens the door to better developing metacommunication skills in supervisees through both online training and the metacommunication supervisory exercise. Areas for continued research are outlined.


Combining routine morphology, p16(INK4a) immunohistochemistry, and in situ hybridization for the detection of human papillomavirus infection in penile carcinomas: a tissue microarray study using classifier performance analyses.
Infection by high-risk human papillomavirus (HR-HPV) plays an important role in the pathogenesis of penile cancer in approximately 50% of the patients. The gold standard for human papillomavirus (HPV) detection is the polymerase chain reaction (PCR) assay. However, technical requirements and associated costs preclude the worldwide use of PCR assays on a routine basis. Herein, we evaluated the predictive abilities of tumor morphology, immunohistochemistry for p16(INK4a) expression, and in situ hybridization (ISH) for HR-HPV detection in defining HPV status, as established by PCR. Tissue samples from 48 patients with HPV-positive penile squamous cell carcinoma (SCC) were included in 4 tissue microarrays (TMA). Sensitivities and specificities were as follows: tumor morphology, 70% and 68%; p16(INK4a) immunohistochemistry, 65% and 90%; HR-HPV ISH, 47% and 100%. Regarding combinations of the predictors, the best performance was seen when HR-HPV ISH and p16(INK4a) immunohistochemistry were combined, regardless of the tumor morphology: sensitivity, 88%; specificity, 64%; area under the receiver-operating characteristic (AUC) curve, 0.83. Combinations of tumor morphology with p16(INK4a) immunohistochemistry or with HR-HPV ISH performed similarly well. In penile SCC, both p16(INK4a) immunohistochemistry and ISH for HR-HPV increase the predictive ability of routine morphology in defining HPV status. These tests can be interpreted differentially, depending on the necessity of a higher sensitivity or a higher specificity. For research/screening studies, we recommend combining tumor morphology, p16(INK4a) immunohistochemistry, and HR-HPV ISH. To increase sensitivity, positivity in any of these predictors should be considered as indicative of HPV infection. For routine diagnosis of clinical cases, criteria should be more stringent, and, to achieve the highest specificity in classifying a case as HPV-related, all predictors should be consistently positive. The data generated in the present study could be used in algorithms for defining HPV status in penile carcinomas.


Ligneous conjunctivitis.
The case history is given of a woman of 65 (in 1973) with a granulomatous conjunctival inflammation in the right eye and chronic recurrent polyps on the vocal cords. Several times, granulomatous tissue was removed from the conjunctiva of the right eye but the result was recurrences at shorter intervals. Seven years after the onset in the right eye the left eye became affected. Various treatments, both systemic and local, were tried without success. The histological diagnosis of ligneous conjunctivitis was not made until 1981. Treatment with the known remedies for ligneous conjunctivitis was not successful. At the end of 1984 treatment with Imuran (azathioprine) was started. Since that time the patient has been practically free of recurrent granulomatous tissue on the conjunctiva and vocal cords. The treatment of ligneous conjunctivitis with Imuran has not previously been reported in the literature.


Efficacy and safety of avelumab plus axitinib in elderly patients with advanced renal cell carcinoma: extended follow-up results from JAVELIN Renal 101.
In the phase III JAVELIN Renal 101 trial, first-line avelumab plus axitinib demonstrated a progression-free survival (PFS) and objective response rate (ORR) benefit versus sunitinib in patients with advanced renal cell carcinoma (aRCC). However, efficacy in elderly patients remains unclear. We report efficacy and safety by age group from the second interim analysis of overall survival (OS). PFS and ORR as per blinded independent central review (RECIST 1.1), OS, and safety were assessed in patient groups aged <65, ≥65 to <75, and ≥75 years. In the avelumab plus axitinib and sunitinib arms, 271/138/33 and 275/128/41 patients aged <65, ≥65 to <75, and ≥75 years, respectively, were randomized. At data cut-off (January 2019), median PFS [95% confidence interval (CI)] with avelumab plus axitinib versus sunitinib in these respective age groups was 11.6 (8.4-19.4) versus 6.9 (5.6-8.4) months [hazard ratio (HR), 0.63; 95% CI 0.501-0.786], 13.8 (11.1-18.0) versus 11.0 (7.8-16.6) months (HR, 0.88; 95% CI 0.627-1.231), and 13.8 [7.0-not estimable (NE)] versus 9.8 (4.3-NE) months (HR, 0.76; 95% CI 0.378-1.511). Median OS (95% CI) in the respective age groups was not reached (NR) (NE-NE) versus 28.6 (25.5-NE) months (HR, 0.74; 95% CI 0.541-1.022), 30.0 (30.0-NE) versus NR (NE-NE) months (HR, 0.89; 95% CI 0.546-1.467), and 25.3 (19.9-NE) versus NR (19.4-NE) months (HR, 0.87; 95% CI 0.359-2.106). ORR (95% CI) in the respective age groups was 49.4% (43.3% to 55.6%) versus 27.3% (22.1% to 32.9%), 60.9% (52.2% to 69.1%) versus 28.9% (21.2% to 37.6%), and 42.4% (25.5% to 60.8%) versus 22.0% (10.6% to 37.6%). In the avelumab plus axitinib arm, grade ≥3 adverse events (AEs) and immune-related AEs occurred in 76.9%/81.2%/72.7% and 45.5%/48.1%/36.4% in the respective age groups. First-line avelumab plus axitinib demonstrated favorable efficacy across age groups, including patients aged ≥75 years. OS data were still immature; follow-up is ongoing. The safety profile was generally consistent across age groups.


An evaluation of traditional and novel tools for lesion behavior mapping.
Kinkingnéhun et al. (Kinkingnéhun, S., Volle, E., Pélégrini-Issac, M., Golmard, J.L., Lehéricy, S., du Boisguéheneuc, F., Zhang-Nunes, S., Sosson, D., Duffau, H., Samson, Y., Levy, R., Dubois, B., 2007. A novel approach to clinical-radiological correlations: Anatomo-Clinical Overlapping Maps (AnaCOM): method and validation. NeuroImage 37: 1237-1249.) have recently described a novel approach for lesion-behavior mapping (LBM), referred to as Anatomo-Clinical Overlapping Maps (AnaCOM). Conventional voxelwise LBM tools apply statistics to contrast behavioral performance of patients with lesions that encompass given voxels to control patients where these voxels are spared. In contrast, AnaCOM contrasts performance of patients with injury involving given voxels to the performance of neurologically healthy participants. The authors correctly note that their procedure can offer substantially more statistical power than conventional LBM methods. We compared AnaCOM to conventional LBM techniques by examining hemiparesis (a common consequence of stroke) as the behavior of interest. We found that AnaCOM detected many regions of the middle cerebral artery territory not associated with the motor system. We suggest that conventional LBM techniques detect regions that are damaged in patients with a deficit while spared in those without a deficit, while AnaCOM detects regions that are associated with a deficit. Therefore, this new measure may offer poor specificity. Furthermore, on theoretical grounds we suggest that permutation-based thresholding will be a more sensitive method for controlling familywise error than the method of counting lesion-overlap clusters used by AnaCOM. Finally, we note that the within group variability tends to be smaller for neurologically healthy controls than in neurological patients, due to ceiling effects. Therefore, we suggest that nonparametric measures or the Welch's t-test are more appropriate than the conventional pooled variance t-test used by AnaCOM.


Effect of oxygen limitation on the content of n-hexadecane-inducible cytochrome P-450 in Acinetobacter calcoaceticus strain EB 104.
The content of cytochrome P-450 as a function of oxygen supply was studied during growth of Acinetobacter on n-hexadecane in batch cultures at constant pH and agitation. The rate of growth and the content of cytochrome P-450 were not affected as long as the dissolved oxygen tension ranged above 3 to 5% of saturation. The amount of cytochrome P-450 increased when the oxygen tension declined to zero. Cytochrome P-450 levels of about 0.3 to 0.4 nmol/mg protein, i.e. a more than a threefold increase, were observed under conditions where oxygen supply was strictly limited and allowed to maintain only a minimum of metabolism or growth. Limited oxygen supply exerted a special effect on the induction of the cytochrome P-450 as concluded from an increasing ratio between cytochrome P-450 and cytochrome o, and from the absence of cytochrome d in cells with elevated content of cytochrome P-450. The increased formation of cytochrome P-450 was a reversible process.


CD4+ T helper 2 cells suppress breast cancer by inducing terminal differentiation.
Cancer immunology research is largely focused on the role of cytotoxic immune responses against advanced cancers. Herein, we demonstrate that CD4+ T helper (Th2) cells directly block spontaneous breast carcinogenesis by inducing the terminal differentiation of the cancer cells. Th2 cell immunity, stimulated by thymic stromal lymphopoietin, caused the epigenetic reprogramming of the tumor cells, activating mammary gland differentiation and suppressing epithelial-mesenchymal transition. Th2 polarization was required for this tumor antigen-specific immunity, which persisted in the absence of CD8+ T and B cells. Th2 cells directly blocked breast carcinogenesis by secreting IL-3, IL-5, and GM-CSF, which signaled to their common receptor expressed on breast tumor cells. Importantly, Th2 cell immunity permanently reverted high-grade breast tumors into low-grade, fibrocystic-like structures. Our findings reveal a critical role for CD4+ Th2 cells in immunity against breast cancer, which is mediated by terminal differentiation as a distinct effector mechanism for cancer immunoprevention and therapy.


CT and MR imaging findings of xanthogranulomatous cholecystitis: correlation with pathologic findings.
The aim of this study was to evaluate CT and MRI findings in xanthogranulomatous cholecystitis (XGC) and to correlate the imaging findings with various pathologic parameters. The study included 13 patients with histopathologically confirmed XGC. The CT ( n=13) and MRI ( n=5) obtained in these patients were evaluated retrospectively. On CT, low-attenuation areas in the wall of XGC correlated with foam and inflammatory cells or necrosis and/or abscess in XGC. Areas of iso- to slightly high signal intensity on T2-weighted images, showing slight enhancement at early phase and strong enhancement at last phase on dynamic study, corresponded with areas of abundant xanthogranulomas. Areas with very high signal intensity on T2-weighted images without enhancement corresponded with necrosis and/or abscesses. Luminal surface enhancement (LSE) of gallbladder wall represented preservation of the epithelial layer. The early-enhanced areas of the liver bed on dynamic CT and MR images corresponded with accumulation of inflammatory cells and abundant fibrosis. Our results indicate that CT and MRI findings correlate well with the histopathologic findings of XGC.


A novel series of non-carboxylic acid, non-hydantoin inhibitors of aldose reductase with potent oral activity in diabetic rat models: 6-(5-chloro-3-methylbenzofuran-2-sulfonyl)-2H-pyridazin-3-one and congeners.
Discovery of a highly selective, potent, and safe non-carboxylic acid, non-hydantoin inhibitor of aldose reductase (AR) capable of potently blocking the excess glucose flux through the polyol pathway that prevails under diabetic conditions has been a long-standing challenge. In response, we did high-throughput screening of our internal libraries of compounds and identified 6-phenylsulfonylpyridazin-2H-3-one, 8, which showed modest inhibition of AR, both in vitro and in vivo. Initial structure-activity relationships concentrated on phenyl substituents and led to 6-(2,4-dichlorophenylsulfonyl)-2H-pyridazin-3-one, 8l, which was more potent than 8, both in vitro and in vivo. Incorporation of extant literature findings with other aldose reductase inhibitors, including zopolrestat, resulted in the title inhibitor, 19m, which is one of the most potent and highly selective non-carboxylic acid, non-hydantoin inhibitors of AR yet described (IC50, 1 nM; ED90 vs sciatic nerve sorbitol and fructose, respectively, 0.8 and 4.0 mg/kg). In rats, its oral bioavailability is 98% and it has a favorable plasma t(1/2) (26 +/- 3 h).


Early human development: neonatal tumours: vascular tumours.
Vascular tumours (haemangiomas and malformations) are common tumours of infancy and childhood. They represent a group of mostly benign conditions, which present early, can grow rapidly and be symptomatic or disfiguring. There are various management options, with different cosmetic and functional outcomes. Haemangiomas and vascular malformations have different clinical courses which dictate respective management; differentiating them is key. Haemangiomas are generally self-limiting after initial proliferation; generally management is conservative. Symptoms can call for treatment. Options include laser, steroids, chemotherapy and surgery. Propanolol, the newest modality of treatment, may have a dramatic effect in problematic lesions. Vascular malformations are a less common group of heterogenous lesions, with some overlap between entities. They do not involute. Treatment options include laser therapy, sclerotherapy, embolisation, and surgery. Emerging therapies include photodynamic therapy and angiogenesis inhibitors. This review will outline the evidence for the various modalities in managing these conditions.


Different response of Acipenser gueldenstaedtii CRP/SAP and SAA to bacterial challenge and chronic thermal stress sheds light on the innate immune system of sturgeons.
Sturgeons are chondrostean fish critically endangered due to anthropogenic loss and degradation of natural habitat and overfishing for meat and caviar production. Consequently, sturgeon aquaculture has extensively developed lately, being Russian sturgeon (Acipenser gueldenstaedtii) the second most important species reared for caviar production. However, Russian sturgeon aquaculture in subtropical countries, such as Uruguay, confronts difficulties because fish have to endure excessive summertime warm temperatures, which weaken their innate defences facilitating opportunistic infections. To address this problem, we look for identifying putative acute phase proteins (APPs), which might be robust serum biomarkers of both infection and chronic thermal stress, applied to monitoring Russian sturgeon health status in farms. We focused on the C-Reactive Protein/Serum Amyloid P (CRP/SAP) pentraxin since the pentraxin family includes well-known APPs, better characterised in mammals than fish. We identified A.gueldenstaedtii CRP/SAP (AgCRP/SAP), as a member of the universal CRP/SAP pentraxin sub-family, and studied AgCRP/SAP involvement in sturgeon response to bacterial challenge and chronic thermal stress, in comparison with A. gueldenstaedtii Serum Amyloid A (AgSAA), a previously described positive APP. Results showed that AgCRP/SAP is a constitutive serum component that remained constant upon Aeromonas hydrophila challenge and chronic thermal stress. Contrastingly, serum AgSAA was subjected to regulation by bacterial and thermal stress challenges, showing a 50-fold increase and 3-fold decline in serum levels, respectively. Overall, results highlight the potential value of AgSAA, but not of AgCRP/SAP, as a biomarker of bacterial infection and the need to continue searching for robust chronic thermal stress biomarkers in sturgeons.


Regioselective formation of alkylidenecyclopropanes from 2-substituted cyclobutylidenes generated from geminal dibromocyclobutanes and methyllithium.
Four different 2-substituted geminal dibromocyclobutanes were reacted with methyllithium at -78 degrees C. In contrast to previous studies using diazocyclobutanes as carbene precursors at temperatures above 200 degrees C via reaction of the corresponding tosylhydrazone sodium salts, the organometallic route in each case produces only an alkylidenecyclopropane that could be isolated in good yields. B3LYP calculations were employed to rationalize the observed regioselective ring contraction of the generated cyclobutyliden(oid)s. [reaction: see text]


Responses of wild plants to nitrate availability : Relationships between growth rate and nitrate uptake parameters, a case study with two Bromus species, and a survey.
Two annual species of Bromus, an invader (B. hordeaceus, ex B. mollis) and a non-invader (B. intermedius), were grown for 28 days in growth chambers, at 5 and 100 μM NO 3- in flowing nutrient solution. No differences between the two species were observed at either NO 3- level, in terms of relative growth rate (RGR) or its components, dry matter partitioning, specific NO 3- absorption rate, nitrogen concentration, and other characteristics of NO 3- uptake and photosynthesis. The effects of decreasing NO 3- concentration in the solution were mainly to decrease the NO 3- concentration in the plants through decreased absorption rate, and to decrease the leaf area ratio through increased specific leaf mass and decreased leaf mass ratio. Organic nitrogen concentration varied little between the two treatments, which may be the reason why photosynthetic rates were not altered. Consequently, RGR was only slightly decreased in the 5-μM treatment compared to the 100-μM treatment. This is in contrast with other species, where growth is reduced at much higher NO 3- concentrations. These discrepancies may be related to differences in RGR, since a log-linear relationship was found between RGR and the NO 3- concentration at which growth is first reduced. In addition, a strong linear relationship was found between the RGR of these species and their maximum absorption rate for nitrate, suggesting that the growth of species with low maximum RGR may be partly regulated by nutrient uptake.


Adoption, Fostering, and Parental Absence in Vanuatu.
Alloparenting, wherein people provide care to children who are not their biological offspring, is a key aspect of human child-rearing. In the Pacific, many children are adopted or fostered by custodial alloparents even when both biological parents are still alive. From a behavioral ecology perspective, such behaviors are puzzling: why parent someone else's child at your expense? Furthermore, little is known about how these arrangements are made in Pacific Islander societies today, who provides care, and what kinds of outcomes fostered children experience. A better understanding of these proximate factors may help reveal the ultimate drivers behind custodial alloparenting. Here, we report findings from a survey carried out with the caregivers of 282 children in rural areas of Vanuatu, an island nation in Melanesia. Most fostered and adopted children lived with relatives such as aunts, uncles, and grandparents (87.5%) rather than unrelated caregivers, with a strong preference for maternal kin. The most common reasons for these arrangements were that the parents had separated (16.7%), were engaging in labor migration (27.1%), or a combination of both (27.1%). Results for investment in children's education and their educational outcomes were mixed, although children removed from crisis situations did more poorly than children removed for aspirational reasons. Our findings suggest that custodial alloparenting helps families adapt to socioeconomic transitions and changing marriage practices. Outcomes may depend on a range of factors, such as the reason children were transferred out of the natal home to begin with.


The modified Clayton-Mannerfelt arthrodesis of the wrist in rheumatoid arthritis: operative technique and report on 93 cases.
Arthrodesis of a painful and destroyed wrist is one of the key operations in patients with rheumatoid arthritis. Clayton is given credit for the first description of an operative technique of wrist arthrodesis by means of an intramedullary Steinmann pin. Mannerfelt popularized this technique by using a Rush pin and additional fixation with staples. The aim of the present article is to give a detailed description of the operative technique used in our hospital. Over a period of 13 years, 104 modified Clayton-Mannerfelt arthrodeses were performed in 87 patients with rheumatoid arthritis. Ninety-three wrists were reviewed clinically and radiographically. The patients had high fusion rates and a reliable reduction in preoperative pain, with a low rate of complications. The pin technique is more versatile than standard wrist arthrodesis plates, and the wrist can be positioned according to the needs of the patient. This technique seems to be a good alternative to conventional wrist arthrodesis using an arthrodesis plate in wrists destroyed by rheumatoid arthritis, even in situations with difficult bone stock. In most cases, it is not necessary to remove the hardware.


Tay-Sachs disease: ultrastructural studies on cultured fibroblasts.
The knowledge that the biochemical lesion associated with Tay-Sachs disease is demonstrable in many tissues, and in particular in cultured fibroblasts, suggested that ultrastructural lesions might also accompany hexosaminidase A deficiency in cultured fibroblasts. Electron microscopic studies on six human skin fibroblast lines and four amniotic fluid fibroblast lines, biochemically confirmed to be deficient in hexosaminidase A, showed characteristic cytoplasmic inclusions not observed in any normal lines studied. Up to 60 of these abnormal cytoplasmic inclusions were observed in full cell cross sections in all affected lines examined.


Rationale for the utilization of interleukin-4, an immune-recognition induced cytokine, in cancer immunotherapy.
Interleukin-2 use for advanced cancer treatment has demonstrated that cytokines are of interest not only in the field of immunology but also in oncology. Interleukin-2 is only one member of the ever-growing family of immune recognition-induced lymphokines. Interleukin-4, a cytokine with pleiotropic effects, shares some common properties with interleukin-2. Availability of recombinant interleukin-4 has led to a better knowledge of this cytokine's functions, and also makes clinical trials possible. This brief review discusses the in vitro and in vivo data that support a potential use of interleukin-4 in cancer immunotherapy.


Key role of quinone in the mechanism of respiratory complex I.
Complex I is the first and the largest enzyme of respiratory chains in bacteria and mitochondria. The mechanism which couples spatially separated transfer of electrons to proton translocation in complex I is not known. Here we report five crystal structures of T. thermophilus enzyme in complex with NADH or quinone-like compounds. We also determined cryo-EM structures of major and minor native states of the complex, differing in the position of the peripheral arm. Crystal structures show that binding of quinone-like compounds (but not of NADH) leads to a related global conformational change, accompanied by local re-arrangements propagating from the quinone site to the nearest proton channel. Normal mode and molecular dynamics analyses indicate that these are likely to represent the first steps in the proton translocation mechanism. Our results suggest that quinone binding and chemistry play a key role in the coupling mechanism of complex I.


Restorative proctocolectomy with J-pouch ileoanal anastomosis for total colonic aganglionosis among neonates and infants.
No consensus exists on the optimal surgical management of total colonic aganglionosis (TCA). Outcomes after restorative proctocolectomy (RPC) as the initial reconstructive procedure among neonatal and infant TCA patients have not been evaluated previously. Medical records of patients with Hirschsprung disease (HD) who underwent RPC during infancy between 1997 and 2012 (n=8) were reviewed. Bowel function and satisfaction with operative results were assessed in a follow-up interview. Median age at RPC was 1.1 months, and covering loop ileostomies were closed 3.7 months later. No operative complications occurred. Hospitalizations for enterocolitis and obstruction occurred each in 50% of patients postoperatively. Enterocolitis-associated outlet obstruction occurred in one third of patients, most of whom responded well to intersphincteric botulinum toxin (botox) injections. No pouchitis or elevated fecal calprotectin levels (median 51 μg/g) were observed. At last follow-up 3.2 years after ileostomy closure, the median 24-hour stooling frequency was 3.5. None had socially limiting fecal incontinence or problems in holding back defecation. Parent satisfaction with operative results was high. The rate of postoperative enterocolitis was similar to other procedures, but a better functional outcome was achieved. Botox injections were effective for postoperative functional outlet obstruction. Short-term results following RPC among neonates and infants are promising.


Efficiency of antibacterial suture material in cardiac surgery: a double-blind randomized prospective study.
Postoperative surgical site infections (SSI) still greatly affect mortality and morbidity in cardiovascular surgery. SSI may be related to the suture material. In this prospective, randomized, controlled, and double-blinded study, the effect of antibacterial suture material on SSI in cardiac surgical patients was investigated. We randomly allocated 510 patients into 2 groups. Antibacterial suture materials were used for wound closure in 170 patients (triclosan-coated suture group), and routine suture materials were used in 340 patients (noncoated suture group). All patients were evaluated for SSI on days 10, 20, and 30 following cardiac surgery. Preoperative risk factors and laboratory findings were comparable for the 2 groups. Sternal infection occurred in 4 (2.4%) of the patients in the triclosan-coated suture group and in 3.5% of the noncoated suture group (P > .05). Leg wound infection occurred in 5 (3.5%) of the patients in the triclosan-coated suture group and in 3.8% of the noncoated suture group (P > .05). Only diabetes mellitus was an independent predictor of SSI. Both noncoated and triclosan-coated suture materials are safe. Larger studies may be needed to show the benefit and cost-effectiveness, if any, of triclosan-coated materials over noncoated materials.


Changes in corneal endothelium after treatment of retinal detachment with intraocular silicone oil.
Keratopathy represents one of the most frequent late complications in eyes with complicated retinal detachment treated with intraocular silicone oil. Corneal examinations including endothelial specular photography were done on 18 silicone treated eyes, 16 of which were aphakic. In addition to widespread silicone oil endothelial contact in 2 eyes, a bubble or droplets of silicone oil were observed in the anterior chamber in 8 eyes. The mean endothelial cell density was lower in the silicone eyes (2076 +/- 196 cells/mm2) as compared to the control fellow eyes (2738 +/- 86 cells/mm2) (P = 0.004). In eyes with silicone oil in the anterior chamber the endothelial cell density was significantly decreased (1857 +/- 232 cells/mm2) (P = 0.005). Obvious endothelial degeneration was noticed when silicone oil had been in the eye for more than a year. Also small droplets of oil with transient contact contributed to its development.