Outcome of severely malnourished children treated according to UNICEF 2004 guidelines: a one-year experience in a zone hospital in rural Ethiopia.
Malnutrition still has a dramatic impact on childhood mortality in sub-Saharan African countries. Very few studies have tried to evaluate the outcome of severely malnourished children treated according to the UNICEF 2004 guidelines and reported fatality rates are still very high. During 2006, 1635 children were admitted to the paediatric ward of St. Luke Catholic Hospital in Wolisso, South West Shewa, Ethiopia. Four hundred and ninety-three (30.15%) were severely malnourished and were enrolled in the study. We reviewed the registration books and inpatient charts to analyze their outcome. A mortality rate of 7.1% was found, which is significantly lower than reported in the literature. 28.6% of deaths occurred within 48 h of admission; the recovery rate was 88.4%; the drop-out rate was 4.5%. Early deaths were due to the poor condition of the children on admission, leading to failure of treatment. Late mortality was considered to be related to electrolyte imbalances, which we were unable to measure. The clinical skills of nursing and medical staff were considered an important factor in improving the outcome of malnourished patients. We found that proper implementation of WHO guidelines for the hospital treatment of severely malnourished children can lead to a relatively low mortality rate, especially when good clinical monitoring is assured.


Current status of parenteral nutrition and enteral nutrition application: an assessment of nutritional prescriptions from 59 hospitals in the People's Republic of China.
The aim of the study reported here was to assess the use of parenteral nutrition (PN) and enteral nutrition (EN), and the prevalence of PN and EN formulas, in the People's Republic of China. Fifty-nine hospitals in the People's Republic of China participated in a nutrition survey. The resulting information on nutritional support was analyzed. We received 379,584 nutritional-support prescriptions over 40 days in 2013. PN provided approximately 63.2% and EN provided approximately 36.8% of nitrogen intake. PN provided 63.5% and EN provided 36.5% of lipid intake. There were obvious differences in nitrogen and lipid intake between PN and EN in different regions, departments, and diseases. The percentage of nourishment provided by PN in different regions was highest in Chengdu, followed by the Beijing, Guangzhou, and Hangzhou areas. The percentage of nourishment provided by PN in different departments was highest in general surgery, followed by gastroenterology and the intensive care unit. The percentage of nourishment provided by PN in different diseases/conditions was highest in acute pancreatitis, followed by cancer, and burns. The main source of nitrogen in PN was balanced amino-acid preparations, and in EN, it was protein. The main source of lipids in PN was long- and medium-chain triglyceride lipid emulsion injection. Despite recent improvements in the application of nutritional support in the People's Republic of China, a much higher percentage of nitrogen and lipids is delivered through PN than through EN. Furthermore, there are marked regional, departmental, and disease-based differences in the selection of PN versus EN. The rationale for use of nutritional support needs to be improved.


3'-Fluoro substitution in the pyridine ring of epibatidine improves selectivity and efficacy for alpha4beta2 versus alpha3beta4 nAChRs.
The analog of epibatidine having a fluoro substituent at the 3' position of the pyridine ring has been recently developed and shown to possess binding affinity in the pM range to alpha4beta2 nAChRs and in the nM range to alpha7 nAChRs and to exhibit potent agonist activity in nicotine-induced analgesia tests. Here we used patch-clamp technique in a whole-cell configuration to compare functional activity of 3'-fluoroepibatidine to that of epibatidine by itself on recombinant alpha4beta2, alpha7 and alpha3beta4 neuronal nAChRs. The agonist effect of (+/-)-epibatidine was partial and yielded comparable EC50s of 0.012 microM (72% efficacy) and 0.027 microM (81% efficacy) at alpha4beta2 and alpha3beta4 nAChRs, respectively, but was full at alpha7 nAChRs with an EC50 of 4.8 muM. Testing of the analog at different concentrations revealed that it acts as a full agonist with an EC50 of 0.36 microM at alpha4beta2 nAChRs and induces partial agonist effect (66% efficacy) at alpha7 nAChRs with an EC50 of 9.8 microM and an IC50 corresponding to 225 microM. In contrast, the analog caused only 24% maximal activation at the range of concentrations from 0.1 to 100 microM and, in addition, induced an inhibition of alpha3beta4 nAChR function with an IC50 of 8.3 microM. Our functional data, which are in agreement with previous binding and behavioral findings, demonstrate that 3'-fluoro substitution in the pyridine ring of epibatidine results in an improved pharmacological profile as observed by an increased efficacy and selectivity for alpha4beta2 versus alpha3beta4 nAChRs.


An engineered PET depolymerase to break down and recycle plastic bottles.
Present estimates suggest that of the 359 million tons of plastics produced annually worldwide1, 150-200 million tons accumulate in landfill or in the natural environment2. Poly(ethylene terephthalate) (PET) is the most abundant polyester plastic, with almost 70 million tons manufactured annually worldwide for use in textiles and packaging3. The main recycling process for PET, via thermomechanical means, results in a loss of mechanical properties4. Consequently, de novo synthesis is preferred and PET waste continues to accumulate. With a high ratio of aromatic terephthalate units-which reduce chain mobility-PET is a polyester that is extremely difficult to hydrolyse5. Several PET hydrolase enzymes have been reported, but show limited productivity6,7. Here we describe an improved PET hydrolase that ultimately achieves, over 10 hours, a minimum of 90 per cent PET depolymerization into monomers, with a productivity of 16.7 grams of terephthalate per litre per hour (200 grams per kilogram of PET suspension, with an enzyme concentration of 3 milligrams per gram of PET). This highly efficient, optimized enzyme outperforms all PET hydrolases reported so far, including an enzyme8,9 from the bacterium Ideonella sakaiensis strain 201-F6 (even assisted by a secondary enzyme10) and related improved variants11-14 that have attracted recent interest. We also show that biologically recycled PET exhibiting the same properties as petrochemical PET can be produced from enzymatically depolymerized PET waste, before being processed into bottles, thereby contributing towards the concept of a circular PET economy.


First occurrence of the non-native bryozoan Schizoporella japonica Ortmann (1890) in Western Europe.
Schizoporella japonica Ortmann was described from Japan but was subsequently introduced on Pacific oysters to the Pacific coast of North America, where it is now well established. In this paper we record it for the first time in European waters. The initial discovery was in a marina at Holyhead, North Wales, in July 2010 but S. japonica has since been observed abundantly in the Orkney Islands (from May 2011) and, subsequently, at other localities in northern Scotland. Introduction seems most likely to have been on an ocean-going vessel. The British material is here fully described and illustrated with SEMs and colour photographs; some unusual characters are discussed. Unlike other recently introduced bryozoans, S. japonica is a cold-water species and its breeding season in Britain extends through the winter. Extensive confusion between this and other species of Schizoporella on the west coast of Canada and the USA led us to make thorough morphometric comparisons between the species concerned (Schizoporella unicornis (Johnston in Wood), Schizoporella errata (Waters) and Schizoporella pseudoerrata Soule, Soule and Chaney). Zooid size in cheilostomate bryozoans is variable and often an unreliable character for species separation but shape (and therefore ratios between variables, which are independent of size) are often valuable: S. japonica zooids have a much greater length:width ratio than the other species. Density of frontal pseudopores provides a useful discriminatory character. Schizoporella unicornis, repeatedly reported in error from the Pacific coast of North America, does not occur there; it is a European species. Full comparisons are made between S. japonica and S. unicornis for European identification and between S. japonica, S. errata and S. pseudoerrata (which are also illustrated) for North American localities.


Phenology, seasonal timing and circannual rhythms: towards a unified framework.
Phenology refers to the periodic appearance of life-cycle events and currently receives abundant attention as the effects of global change on phenology are so apparent. Phenology as a discipline observes these events and relates their annual variation to variation in climate. But phenology is also studied in other disciplines, each with their own perspective. Evolutionary ecologists study variation in seasonal timing and its fitness consequences, whereas chronobiologists emphasize the periodic nature of life-cycle stages and their underlying timing programmes (e.g. circannual rhythms). The (neuro-) endocrine processes underlying these life-cycle events are studied by physiologists and need to be linked to genes that are explored by molecular geneticists. In order to fully understand variation in phenology, we need to integrate these different perspectives, in particular by combining evolutionary and mechanistic approaches. We use avian research to characterize different perspectives and to highlight integration that has already been achieved. Building on this work, we outline a route towards uniting the different disciplines in a single framework, which may be used to better understand and, more importantly, to forecast climate change impacts on phenology.


A study of malnutrition in Iranian patients with primary antibody deficiency.
Nutrition is an important factor that influences immunity, and nutritional deficiencies can impair resistance to infections. Malnutrition is the most common cause of immunodeficiency worldwide. Trace elements such as zinc, selenium, iron, and copper can influence several components of immunity. Primary antibody deficiency disorders are a group of disorders characterized by an unusual susceptibility to infections and malnutrition. Impaired nutritional status has been reported in immunodeficient patients. The aim of this study was to determine anthropometric indices and trace elements status in these patients. Thirty-eight children (28 males, 10 females, aged 2-18 years) with primary antibody deficiency referring to Children's Medical Center of Tehran University of Medical Science were enrolled in this research. Primary immunodeficiency disorders consisting of CVID, XLA, IgA deficiency, IgG subclass deficiency, and hyper IgM were assessed. Anthropometric indices, comprised of height, weight that were measured and body mass index (BMI) was calculated. Height-for-age (HAZ), weight-for-height (WHZ) and weight-for-age (WAZ) were determined according to Z-score to study mild, moderate and severe malnutrition. Serum copper, zinc, selenium and iron levels were measured by an atomic absorption spectrometer. The most common disorders were CVID 52.5% and X-linked agammaglobulinaemia 27.5%. Based on BMI measurements 21.1% of patients had malnutrition. According to HAZ, 13.2%, 13.2% and 36.8% had severe, moderate and mild malnutrition, respectively. According to WAZ, 10.5%, 18.4% and 28.6% had severe, moderate and mild malnutrition, respectively. Regarding to WHZ, 14.3% and 28.6% had moderate and mild malnutrition, respectively. Low selenium levels and high copper levels were observed in 37.5% and 70.3%, respectively. Anthropometric data showed that the frequency of malnutrition in these patients was higher than the CDC standard. Low serum selenium levels and high serum copper levels were observed, suggesting further research is needed on these parameters. Most of the patients had serum zinc and iron levels within the normal range. It is recommeded that clinical immunologists and nutritionists should make a collective effort to provide these patients with standard or specialized diets so as to decrease the risk of infection.


Must consent always be obtained for a do-not-resuscitate order?
Using cardiopulmonary resuscitation for cardiac or respiratory arrest unless there is an explicit do-not-resuscitate order is a policy adopted by all hospitals. Such a policy usually requires the patient's (or surrogate's) consent for a do-not-resuscitate order to be instituted. This article, however, presents the argument that consent need not always be obtained. In the case discussed, the well-being of the patient, other patients, and the health care providers all support a unilateral decision by the physician not to attempt resuscitation at the time of death. The medical community and society need to acknowledge that such cases exist and to develop policies that respect not only the interests of patients but also those of health care providers and society.


Optimization-based learning with bounded error for feedforward neural networks.
An optimization-based learning algorithm for feedforward neural networks is presented, in which the network weights are determined by minimizing a sliding-window cost. The algorithm is particularly well suited for batch learning and allows one to deal with large data sets in a computationally efficient way. An analysis of its convergence and robustness properties is made. Simulation results confirm the effectiveness of the algorithm and its advantages over learning based on backpropagation and extended Kalman filter.


The transfusion service laboratory in virtual reality.
Due to the global SARS-CoV-2 pandemic, in-person laboratory medicine clerkships were converted to distance learning. The remote clerkship format provided advantages of allowing participation of students from more locations and greater scheduling flexibility but provided new challenges of maintaining learner engagement and providing experiential content of the laboratory environment. Gamification of educational content is one educational modality that has shown effectiveness in a multitude of different contexts to increase learner engagement and retention. Therefore, we created an interactive, educational 360° virtual reality walkthrough tour using off-the-shelf commercially available 360° cameras and software of the Transfusion service and Microbiology Laboratories. The process consists of taking multiple 360° still-images within the space, color-correction, blurring the faces of staff or sensitive information, adding navigation buttons, and other interactive elements. The virtual tours were used for both recruitment and education with further plans to integrate the learning modality into the curriculum. The clerkship is likely to remain as partially or fully as remote learning so such walkthrough tours will continue to remain relevant. This technology can be applied globally to other departments and institutions for education or recruitment.


Lactoquinomycin, a novel anticancer antibiotic. I. Taxonomy, isolation and biological activity.
Lactoquinomycin, a novel basic antibiotic, was isolated from the culture broth of a soil streptomyces by repeated solvent extraction and adsorption column chromatography. Morphological, cultural and physiological studies revealed that the organism belongs to the species Streptomyces tanashiensis. The antibiotic was active against bacteria, particularly Gram-positive organisms, and neoplastic cells in vitro. Antibiotic-resistant cell sublines of L5178Y lymphoblastoma were more significantly inhibited by lactoquinomycin than the parental cell line. Lactoquinomycin was effective against Ehrlich carcinoma in mice.


Development of a cardiac technician led paediatric echocardiographic service--experience from a district general hospital in the United Kingdom.
To report our experience in providing cardiac technician led paediatric echocardiography services in a district general hospital in the United Kingdom. We have collected prospectively the numbers of referrals, and the proportion of abnormal echocardiograms, since inception of the service in 2000. In additional, for a period of 12 months, we have audited in detail the patterns of referral to the service, and outcomes, assessing the effect of the service on the outreach clinic run by a visiting paediatric cardiologist. Use of the system resulted in detection of a wide range of abnormalities, with our audit showing that the patients received appropriate management. The total referrals to the service increased 10 fold over the 4 year period of the study. The proportion of abnormal hearts detected by echocardiography, however, dropped from 90 per cent to 16 per cent over the same period. The numbers of patients seen in the outreach cardiology clinic remained unaltered. Having been proved to be an effective model for the triage of children with suspected congenital cardiac disease, adoption of a cardiac technician led echocardiographic service has seen a dramatic increase in the numbers of echocardiograms requested, without decreasing the workload of the visiting paediatric cardiologist.


Adding ketoprofen to intravenous patient-controlled analgesia with tramadol after major gynecological cancer surgery: a double-blinded, randomized, placebo-controlled clinical trial.
Ketoprofen is a NSAIDs of the 2-aryl propionic acid class commonly used in the treatment of inflammatory rheumatic disease, acute pain and fever. Clinically, ketoprofen seems to reduce morphine requirements by 33 to 40% with ketoprofen's supposed central mechanism of analgesia. We evaluated the efficacy and safety of intravenous (IV) ketoprofen as an adjuvant to IV PCA (patient controlled analgesia) with tramadol after major gynecological cancer surgery for postoperative analgesia. Fifty patients were enrolled in this double-blinded, randomized, placebo-controlled study. Patients were allocated randomly to two groups: group I (25 patients) served as a control group, with patients receiving saline; group II (25 patients) received ketoprofen. Patients received an intravenous bolus of saline or 100 mg ketoprofen at the end of surgery. Then, PCA was given as a 20 mg tramadol bolus and 10 min lockout time. Pain relief was regularly assessed using a visual analog scale. Tramadol consumption, side-effects, and patient satisfaction were noted during the 24 hours after the surgery. No significant difference was observed in pain score, side-effects and patient satisfaction between the groups (p > 0.05). The cumulative PCA-tramadol consumption was lower in the ketoprofen-treated patients than placebo-treated patients (p < 0.05). Our results demonstrate that a single dose of 100 mg ketoprofen reduced tramadol consumption for treatment of postoperative pain after major gynecological cancer surgery.


Multiple endocrine adenoma syndrome.
The case history of a 40-year-old woman with a fatal haemorrhage from a duodenal ulcer, jejunitis, renal lithiasis, hypertrophy of the adrenal glands, multiple adenomas of the pancreas, and three adenomas of both the parathyroid and pituitary glands is reported. Though there was histological evidence, in the bones, of hyperparathyroidism, the serum levels of calcium, phosphorus, and phosphatase and the urinary excretion of calcium were normal. The significance of low calcium and high phosphorus excretion in the urine as an indication of parathyroid disorder is discussed."Multiple endocrine adenoma syndrome" is suggested as the appropriate designation for the clinical disorders in which adenomas of one or more endocrine glands are associated with disorders of the alimentary tract when patients present with recurrent peptic ulceration, pancreatic dysfunction, or watery diarrhoea.


"If I only knew:" a patient education program on advance directives.
This article describes a unique renal patient education program on advance directives. It explains why the program was developed, the components of the program and their use, and the effects of the program. It is argued that programs like this one are needed to provide patients with reliable information about advance directives in a sensitive, time efficient manner.


Life Detection and Microbial Biomarker Profiling with Signs of Life Detector-Life Detector Chip During a Mars Drilling Simulation Campaign in the Hyperarid Core of the Atacama Desert.
The low organic matter content in the hyperarid core of the Atacama Desert, together with abrupt temperature shifts and high ultraviolet radiation at its surface, makes this region one of the best terrestrial analogs of Mars and one of the best scenarios for testing instrumentation devoted to in situ planetary exploration. We have operated remotely and autonomously the SOLID-LDChip (Signs of Life Detector-Life Detector Chip), an antibody microarray-based sensor instrument, as part of a rover payload during the 2019 NASA Atacama Rover Astrobiology Drilling Studies (ARADS) Mars drilling simulation campaign. A robotic arm collected drilled cuttings down to 80 cm depth and loaded SOLID to process and assay them with LDChip for searching for molecular biomarkers. A remote science team received and analyzed telemetry data and LDChip results. The data revealed the presence of microbial markers from Proteobacteria, Acidobacteria, Bacteroidetes, Actinobacteria, Firmicutes, and Cyanobacteria to be relatively more abundant in the middle layer (40-50 cm). In addition, the detection of several proteins from nitrogen metabolism indicates a pivotal role in the system. These findings were corroborated and complemented on "returned samples" to the lab by a comprehensive analysis that included DNA sequencing, metaproteomics, and a metabolic reconstruction of the sampled area. Altogether, the results describe a relatively complex microbial community with members capable of nitrogen fixation and denitrification, sulfur oxidation and reduction, or triggering oxidative stress responses, among other traits. This remote operation demonstrated the high maturity of SOLID-LDChip as a powerful tool for remote in situ life detection for future missions in the Solar System.


Less Is More: Implementing the Minimal Intervention Needed for Change Approach to Increase Contextual Fit of Speech-Language Interventions.
Speech-language pathologists (SLPs) and researchers face difficulties in moving evidence-based practices from clinical research into widespread practice, in part due to a mismatch between the design of typical intervention research studies and the realities of clinical settings. SLPs must adapt interventions from the literature or established programs to fit the needs of specific clients and settings. Researchers must design studies that better reflect clinical practice. Here, we provide an overview of the Minimal Intervention Needed for Change (MINC) approach, a systematic approach to developing and adapting interventions that focuses on achieving meaningful outcomes within specific contexts. We outline the principles of MINC and illustrate this process through the use of a case study. MINC can support systematic development and adaptation of interventions in clinical and research settings, particularly settings with resource limitations. Researchers should work to align research intervention work with typical clinical settings. This involves both targeting outcomes that are functional and clinically significant and acknowledging resource limitations. SLPs should adapt evidence-based interventions systematically and carefully to meet the needs of clients and settings while retaining the core components of intervention that result in meaningful change for clients.


Brain NAD Is Associated With ATP Energy Production and Membrane Phospholipid Turnover in Humans.
The brain requires a large amount of energy, mostly derived from the metabolism of glucose, which decreases substantially with age and neurological diseases. While mounting evidence in model organisms illustrates the central role of brain nicotinamide adenine dinucleotide (NAD) for maintaining energy homeostasis, similar data are sparse in humans. This study explores the correlations between brain NAD, energy production and membrane phospholipid metabolism by 31-phosphorous magnetic resonance spectroscopy (31P-MRS) across 50 healthy participants including a young (mean age 27.1-year-old) and middle-aged (mean age 56.4-year-old) group. The analysis revealed that brain NAD level and NAD+/NADH redox ratio were positively associated with ATP level and the rate of energy production, respectively. Moreover, a metabolic network linking NAD with membrane phospholipid metabolism, energy production, and aging was identified. An inverted trend between age and NAD level was detected. These results pave the way for the use of 31P-MRS as a powerful non-invasive tool to support the development of new therapeutic interventions targeting NAD associated phospho-metabolic pathways in brain aging and neurological diseases.


A synaptic mechanism for network synchrony.
Within neural networks, synchronization of activity is dependent upon the synaptic connectivity of embedded microcircuits and the intrinsic membrane properties of their constituent neurons. Synaptic integration, dendritic Ca(2+) signaling, and non-linear interactions are crucial cellular attributes that dictate single neuron computation, but their roles promoting synchrony and the generation of network oscillations are not well understood, especially within the context of a defined behavior. In this regard, the lamprey spinal central pattern generator (CPG) stands out as a well-characterized, conserved vertebrate model of a neural network (Smith et al., 2013a), which produces synchronized oscillations in which neural elements from the systems to cellular level that control rhythmic locomotion have been determined. We review the current evidence for the synaptic basis of oscillation generation with a particular emphasis on the linkage between synaptic communication and its cellular coupling to membrane processes that control oscillatory behavior of neurons within the locomotor network. We seek to relate dendritic function found in many vertebrate systems to the accessible lamprey central nervous system in which the relationship between neural network activity and behavior is well understood. This enables us to address how Ca(2+) signaling in spinal neuron dendrites orchestrate oscillations that drive network behavior.


The role of probiotics in the clinical management of food allergy and atopic dermatitis.
The probiotics are cultures of potentially beneficial bacteria that positively affects host by enhancing the microbial balance and therefore restore the normal intestinal permeability and gut microecology, improve the intestine's immunologic barrier function and reduce the generation of proinflammatory cycochines characteristics of allergic inflammation. The authors made a survey of the most relevant studies concerning the use of probiotics in the food allergy, atopic dermatitis, and in primary prevention of atopy. On the basis of these trials probiotic therapy alleviates allergic inflammation as demonstrated by the control of clinical symptoms and the reduction of local and systemic inflammatory markers.


Evaluation of outcome of transurethral needle ablation for treating symptomatic benign prostatic hyperplasia: A 10-year experience.
The aim of this study is to report our 10-year experience with transurethral needle ablation (TUNA) to evaluate its outcome on long-term basis. A total of 351 patients' records who underwent TUNA procedure for the management of benign prostatic hyperplasia were reviewed. The International Prostate Symptom Score (IPSS) and peak urinary flow rate were evaluated before the procedure, at 3 and 6 months postoperatively, and then yearly for 10 years. For patients complaining of de novo erectile dysfunction, the International Index of Erectile Function-5 was evaluated. Postoperative complications, number of patients who required additional therapeutic modality/other TUNA sessions, or those dropped out during follow-up were all recorded. Three hundred and fifty-one patients who underwent TUNA with fulfillment of our selection criteria were included in the study. The yearly records of included patients showed that patients' baseline IPSS was significantly improved all over the follow-up years. Similarly, the maximum flow rate of the patients was significantly improved during the next 8 years. About 96.4% of patients who underwent TUNA did not require additional therapeutic modality/other TUNA sessions during the 1st-year follow-up. However, by 10 years, 26.4% of patients were offered another TUNA session and shifted to either medical therapy or other minimally invasive therapies. Mild hematuria was the most common complication (85.7%). Urinary retention, urethral stricture, and de novo erectile dysfunction were developed in 15.1%, 1.7%, and 6.8% of patients, respectively. There were no cases of retrograde ejaculation. TUNA can be considered as a relatively effective technique with a good safety profile. The current study demonstrated both significant subjective and objective improvements over 10 and 8 years of follow-up, respectively. It can be considered as a preferable option for patients who prefer surgical option with preservation of their sexual function and fertility.


A convergence analysis of unconstrained and bound constrained evolutionary pattern search.
We present and analyze a class of evolutionary algorithms for unconstrained and bound constrained optimization on R(n): evolutionary pattern search algorithms (EPSAs). EPSAs adaptively modify the step size of the mutation operator in response to the success of previous optimization steps. The design of EPSAs is inspired by recent analyses of pattern search methods. We show that EPSAs can be cast as stochastic pattern search methods, and we use this observation to prove that EPSAs have a probabilistic, weak stationary point convergence theory. This convergence theory is distinguished by the fact that the analysis does not approximate the stochastic process of EPSAs, and hence it exactly characterizes their convergence properties.


Understanding the Buffering Effects of Protective Factors on the Relationship between Adverse Childhood Experiences and Teen Dating Violence Perpetration.
Prior research has demonstrated the scope and impact of adverse childhood experiences (ACEs) on health and wellbeing. Less is known about the trajectories from exposure to ACEs, such as witnessing family conflict and violence in the community, to teen dating violence perpetration, and the protective factors that buffer the association between early exposure to ACEs and later teen dating violence perpetration. Students (n = 1611) completed self-report surveys six times during middle and high school from 2008 to 2013. In early middle school, the sub-sample was 50.2% female and racially/ethnically diverse: 47.7% Black, 36.4% White, 3.4% Hispanic, 1.7% Asian/Pacific Islander, and 10.8% other. Youth were, on average, 12.7 years old. Latent transition analysis was used to assess how trajectories of exposure to parental conflict and community violence during middle school transition into classes of teen dating violence perpetration (e.g., sexual, physical, threatening, relational, and verbal) in high school. Protective factors were then analyzed as moderators of the transition probabilities. Three class trajectories of ACEs during middle school were identified: decreasing family conflict and increasing community violence (n = 103; 6.4%), stable low family conflict and stable low community violence (n = 1027; 63.7%), stable high family conflict and stable high community violence (n = 481; 29.9%). A three class solution for teen dating violence perpetration in high school was found: high all teen dating violence class (n = 113; 7.0%), physical and verbal only teen dating violence class (n = 335; 20.8%), and low all teen dating violence class (n = 1163; 72.2%). Social support, empathy, school belonging and parental monitoring buffered some transitions from ACEs exposure trajectory classes to teen dating violence perpetration classes. Comprehensive prevention strategies that address multiple forms of violence while bolstering protective factors across the social ecology may buffer negative effects of exposure to violence in adolescence.


Comparison of methods for assessing in vitro antibiotic synergism against Pseudomonas and Serratia.
Infections with Pseudomonas aeruginosa and Serratia marcescens are often difficult to treat because of the narrow therapeutic ratio of available antimicrobials. Synergistic inhibitory and bactericidal activity for gentamicin and carbenicillin against P. aeruginosa has been documented in vitro. The purpose of this study was to compare 4 methods of determining in vitro synergism between several aminoglycosides and penicillins. The agar dilution method using an inoculum replicator was employed, and a drug combination showing inhibition equal to or less than one-fourth of the individual minimal inhibitory concentrations was termed synergistic. Combinations using amikacin and BL-P1654 showed synergism against a greater per cent of strains of P. aeruginosa and S. marcescens than combinations using gentamicin or carbenicillin. Additionally, the "checkerboard" broth dilution method using both minimal inhibitory concentration and minimal bactericidal concentration as endpoints and killing curves according to the methods of Jawetz was studied. Comparison of the results of these 4 methods showed excellent correlation, verifying the consistency of the 4 techniques for determining in vitro synergism.


Role of Peptides in Diagnostics.
The specificity of a diagnostic assay depends upon the purity of the biomolecules used as a probe. To get specific and accurate information of a disease, the use of synthetic peptides in diagnostics have increased in the last few decades, because of their high purity profile and ability to get modified chemically. The discovered peptide probes are used either in imaging diagnostics or in non-imaging diagnostics. In non-imaging diagnostics, techniques such as Enzyme-Linked Immunosorbent Assay (ELISA), lateral flow devices (i.e., point-of-care testing), or microarray or LC-MS/MS are used for direct analysis of biofluids. Among all, peptide-based ELISA is considered to be the most preferred technology platform. Similarly, peptides can also be used as probes for imaging techniques, such as single-photon emission computed tomography (SPECT) and positron emission tomography (PET). The role of radiolabeled peptides, such as somatostatin receptors, interleukin 2 receptor, prostate specific membrane antigen, αβ3 integrin receptor, gastrin-releasing peptide, chemokine receptor 4, and urokinase-type plasminogen receptor, are well established tools for targeted molecular imaging ortumor receptor imaging. Low molecular weight peptides allow a rapid clearance from the blood and result in favorable target-to-non-target ratios. It also displays a good tissue penetration and non-immunogenicity. The only drawback of using peptides is their potential low metabolic stability. In this review article, we have discussed and evaluated the role of peptides in imaging and non-imaging diagnostics. The most popular non-imaging and imaging diagnostic platforms are discussed, categorized, and ranked, as per their scientific contribution on PUBMED. Moreover, the applicability of peptide-based diagnostics in deadly diseases, mainly COVID-19 and cancer, is also discussed in detail.


High-Intensity Training and Salivary Immunoglobulin A Responses in Professional Top-Level Soccer Players: Effect of Training Intensity.
Owen, AL, Wong, DP, Dunlop, G, Groussard, C, Kebsi, W, Dellal, A, Morgans, R, and Zouhal, H. High-intensity training and salivary immunoglobulin A responses in professional top-level soccer players: Effect of training intensity. J Strength Cond Res 30(9): 2460-2469, 2016-This study aimed (a) to test the hypothesis that salivary immunoglobulin A (s-IgA) would vary with training intensity sessions (low-intensity [LI] vs. high-intensity sessions [HI]) during a traditional training program divided into 4 training periods and (b) to identify key variables (e.g., GPS data, rating of perceived exertion [RPE], and training duration), which could affect s-IgA. Saliva samples of 10 elite professional soccer players were collected (a) before the investigation started to establish the baseline level and (b) before and after each 4 training sessions (LI vs. HI). Training intensity was monitored as internal (through heart rate responses and RPE) and external (through GPS) loads. High-intensity sessions were associated with higher external load (GPS) and with higher RPE. Baseline and pretraining s-IgA did not differ between the 4 training sessions both for HI and LI. Post-training s-IgA were not different (in absolute value and in percentage of change) between HI and LI sessions at the first 3 periods. However, at the fourth period, s-IgA concentration for HI session was significantly lower (p ≤ 0.05) than the LI session. The percentage change between s-IgA post-training and s-IgA baseline concentrations differ significantly (p ≤ 0.05) between HI and LI training sessions. Significant correlations between s-IgA and training intensity were also noted. High-intensity soccer training sessions might cause a significant decrease in s-IgA values during the postexercise window as compared with LI sessions. This study encourages coaches to monitor s-IgA in routine, particularly during HI training periods, to take precautions to avoid upper respiratory tract infection in highly trained soccer players.


Raman spectroscopic study on the copper(II) binding mode of prion octapeptide and its pH dependence.
The cellular form of prion protein is a precursor of the infectious isoform, which causes fatal neurodegenerative diseases through intermolecular association. One of the characteristics of the prion protein is a high affinity for Cu(II) ions. The site of Cu(II) binding is considered to be the N-terminal region, where the octapeptide sequence PHGGGWGQ repeats 4 times in tandem. We have examined the Cu(II) binding mode of the octapeptide motif and its pH dependence by Raman and absorption spectroscopy. At neutral and basic pH, the single octapeptide PHGGGWGQ forms a 1:1 complex with Cu(II) by coordinating via the imidazole N pi atom of histidine together with two deprotonated main-chain amide nitrogens in the triglycine segment. A similar 1:1 complex is formed by each octapeptide unit in (PHGGGWGQ)2 and (PHGGGWGQ)4. Under weakly acidic conditions (pH approximately 6), however, the Cu(II)-amide- linkages are broken and the metal binding site of histidine switches from N pi to N tau to share a Cu(II) ion between two histidine residues of different peptide chains. The drastic change of the Cu(II) binding mode on going from neutral to weakly acidic conditions suggests that the micro-environmental pH in the brain cell regulates the Cu(II) affinity of the prion protein, which is supposed to undergo pH changes in the pathway from the cell surface to endosomes. The intermolecular His(N tau)-Cu(II)-His(N tau) bridge may be related to the aggregation of prion protein in the pathogenic form.


Moyamoya syndrome associated with neurofibromatosis type I in a pediatric patient.
Neurofibromatosis type 1 (NF-1) is the most prevalent autosomal dominant genetic disorder among humans. Moyamoya disease is a cerebral vasculopathy that is only rarely observed in association with NF-1, particularly in the pediatric age range. The present study reports an occurrence of this association in an infant. An eight-month-old female presented convulsive seizures with clonic movements. The patient suffered an ischemic stroke with hemiparesis. Magnetic resonance imaging revealed radiological findings compatible with moyamoya disease. The diagnosis of NF-1 was made at the age of 20 months. Despite the rarity of this association in childhood, children with focal neurological symptoms and a diagnosis of NF-1 deserve to be investigated for moyamoya syndrome.


Blobs and curves: object-based colocalisation for plant cells.
Blobs and curves occur everywhere in plant bioimaging: from signals of fluorescence-labelled proteins, through cytoskeletal structures, nuclei staining and cell extensions such as root hairs. Here we look at the problem of colocalisation of blobs with blobs (protein-protein colocalisation) and blobs with curves (organelle-cytoskeleton colocalisation). This article demonstrates a clear quantitative alternative to pixel-based colocalisation methods and, using object-based methods, can quantify not only the level of colocalisation but also the distance between objects. Included in this report are computational algorithms, biological experiments and guidance for those looking to increase their use of computationally-based and quantified analysis of bioimages.


Preoperative lymphoscintigraphy for breast cancer does not improve the ability to identify axillary sentinel lymph nodes.
To evaluate the role of preoperative lymphoscintigraphy in sentinel lymph node (SLN) biopsy for breast cancer. Numerous studies have demonstrated that SLN biopsy can be used to stage axillary lymph nodes for breast cancer. SLN biopsy is performed using injection of radioactive colloid, blue dye, or both. When radioactive colloid is used, a preoperative lymphoscintigram (nuclear medicine scan) is often obtained to ease SLN identification. Whether a preoperative lymphoscintigram adds diagnostic accuracy to offset the additional time and cost required is not clear. After informed consent was obtained, 805 patients were enrolled in the University of Louisville Breast Cancer Sentinel Lymph Node Study, a multiinstitutional study involving 99 surgeons. Patients with clinical stage T1-2, N0 breast cancer were eligible for the study. All patients underwent SLN biopsy, followed by level I/II axillary dissection. Preoperative lymphoscintigraphy was performed at the discretion of the individual surgeon. Biopsy of nonaxillary SLNs was not required in the protocol. Chi-square analysis and analysis of variance were used for statistical comparison. Radioactive colloid injection was performed in 588 patients. In 560, peritumoral injection of isosulfan blue dye was also performed. A preoperative lymphoscintigram was obtained in 348 of the 588 patients (59%). The SLN was identified in 221 of 240 patients (92.1%) who did not undergo a preoperative lymphoscintigram, with a false-negative rate of 1.6%. In the 348 patients who underwent a preoperative lymphoscintigram, the SLN was identified in 310 (89.1%), with a false-negative rate of 8.7%. A mean of 2.2 and 2. 0 SLNs per patient were removed in the groups without and with a preoperative lymphoscintigram, respectively. There was no statistically significant difference in the SLN identification rate, false-negative rate, or number of SLNs removed when a preoperative lymphoscintigram was obtained. Preoperative lymphoscintigraphy does not improve the ability to identify axillary SLN during surgery, nor does it decrease the false-negative rate. Routine preoperative lymphoscintigraphy is not necessary for the identification of axillary SLNs in breast cancer.


[Nisin inactivation in a culture of the producer Streptococcus lactis strain MGU].
The intensive biosynthesis of nizin on the glucose-yeast medium is observed during the logarithmic and early lag phases of the staphylococcal growth. The ratio of nizin in the fermentation broth (free nazin) and that bound with the cells depended on pH of the medium. When pH was maintained at 6.6-6.8, the amount of nazin in the cells during and growth logarithmic phase was equal to its amount in the fermentation broth filtrate. During the lag phase marked inactivation of nizin was noted. periodical feeding of casein prevented the nizin inactivation. The preliminary data are indicative of the enzymatic nature of the antibiotic.


Methylome sequencing in triple-negative breast cancer reveals distinct methylation clusters with prognostic value.
Epigenetic alterations in the cancer methylome are common in breast cancer and provide novel options for tumour stratification. Here, we perform whole-genome methylation capture sequencing on small amounts of DNA isolated from formalin-fixed, paraffin-embedded tissue from triple-negative breast cancer (TNBC) and matched normal samples. We identify differentially methylated regions (DMRs) enriched with promoters associated with transcription factor binding sites and DNA hypersensitive sites. Importantly, we stratify TNBCs into three distinct methylation clusters associated with better or worse prognosis and identify 17 DMRs that show a strong association with overall survival, including DMRs located in the Wilms tumour 1 (WT1) gene, bi-directional-promoter and antisense WT1-AS. Our data reveal that coordinated hypermethylation can occur in oestrogen receptor-negative disease, and that characterizing the epigenetic framework provides a potential signature to stratify TNBCs. Together, our findings demonstrate the feasibility of profiling the cancer methylome with limited archival tissue to identify regulatory regions associated with cancer.


Meningiomas occurring during long-term survival after treatment for childhood cancer.
Childhood cancer is rare but improvements in treatment over the past five decades have resulted in a cohort of more than 30,000 long-term survivors of childhood cancer in the UK with more added annually. These long-term survivors are at risk of late effects of cancer treatment which replace original tumour recurrence as the leading cause of premature death. Second neoplasms are a particular risk and in the central nervous system meningiomas occur increasingly with increased radiation dose to central nervous system tissue and length of time after exposure, resulting in a 500-fold increase above that expected in the normal population by 40 years of follow up. This multidisciplinary author group and others met to discuss the issue. Our pooled information, and consensus that screening should only follow symptoms, was published online by the Royal College of Radiologists in 2013. We outline here the current knowledge and management of these neoplasms secondary to childhood cancer treatment.


[The immunological aspects of a hip joint lesion in childhood].
The paper presents an in-depth analysis of immunological mechanisms of the hip joint synovitis development in children. Studied in the pediatric patients with transient coxitis, Perthes disease, and tuberculous coxitis (n = 54, 15, and 15 respectively) with the aid of flow cytofluorometer FACStar PLUS was the subpopulation of immunocompetent cells with a wide spectrum of MCAB. Controls (n = 35) were sex and age-matched. Comparative analysis of immunological parameters in the above children disclosed a toxic-and-allergic origination of transient synovitis with predominant affection of the T-cell link of immunity (T-helpers failure and activation of T-suppressors). Joint mucose injury was noted to be developing against the background of reduction of serum IgA. Activation of non-specific mechanisms (natural killers, increase in SDH activity) is of compensatory character. Mechanisms of activation of cell processes (expression of panmitogenic receptor CD4+ antigen) in Perthes disease warrant further studies. In patients with tuberculous coxitis, immunological incompetence develops in the presence of cytotoxic reactions and activation of the B-link, with the production of IgM being on the increase but with no essential changes in the IgG fraction. It is necessary that selective stimulators of T-helpers be included into the treatment scheme together with drugs capable of exerting a selective effect on the T-link of immunity.


Assessment of geometrical remodelling of the aortic arch after hybrid treatment.
The aim of this study was to measure the morphological remodelling of the ascending aorta, aortic arch and thoracic aorta after aortic arch hybrid treatment including debranching and stent graft implantation. Preoperative, 1-month and 1-year follow-up of computed tomography angiography scans of 22 patients were analysed to compute the lumen centreline from the aortic root to the coeliac trunk, and the following measurements were derived: the total centreline length, distance from the aortic root to the left subclavian artery, distance from the left subclavian artery to the distal landing zone. For both pre- and postoperative centrelines, the pointwise curvature was measured at the proximal and the distal landing zones. The mean curvature values of the whole aortic segment and the endografting region of the ascending and the descending aorta were measured. Surface outerline was computed as well, and curvature values at the endograft landing points were extracted. At the 1-month follow-up, centreline length were already significantly increased (382.66 ± 48.69 to 388.1 ± 50.75 mm; P = 0.01). Centreline pointwise curvature increased in the proximal (+29%, P = 0.011) and the distal zones (+63%, P = 0.004). Similarly, pointwise curvature of the outerline significantly increased in the proximal (+77%, P = 0.01) and the distal landing zones (+100%, P = 0.04). The centreline mean curvature increased in the ascending aorta (+7%, P = 0.02) and decreased in the endografting region (-3.3%, P = 0.004). No evidence of a relationship of such a remodelling with the type of endograft and the type of pathology was observed. This remodelling trend was confirmed by the analysis of 1-year computed tomography angiographies. Hybrid arch repair was associated with a significant elongation of the vessel and a significant increase in the curvature on the ascending aorta and the descending aorta and on the endograft proximal and the distal landing zones.


Medical Humanities Teaching in North American Allopathic and Osteopathic Medical Schools.
Although the AAMC requires annual reporting of medical humanities teaching, most literature is based on single-school case reports and studies using information reported on schools' websites. This study sought to discover what medical humanities is offered in North American allopathic and osteopathic undergraduate medical schools. An 18-question, semi-structured survey was distributed to all 146 (as of June 2016) member schools of the American Association of Medical Colleges and the American Association of Colleges of Osteopathic Medicine. The survey sought information on required and elective humanities content, hours of humanities instruction, types of disciplines, participation rates, and humanities administrative structure. The survey was completed by 134 schools (145 AAMC; 31 AACOM). 70.8% of schools offered required and 80.6% offered electives in humanities. Global health and writing were the most common disciplines. Schools required 43.9 mean (MD 45.4; DO 37.1) and 30 (MD 29; DO 37.5) median hours in humanities. In the first two years, most humanities are integrated into other course work; most electives are offered as stand-alone classes. 50.0% of schools report only 0-25% of students participating in humanities electives. Presence of a certificate, concentration or arts journal increased likelihood of humanities content but decreased mean hours. Schools with a medical humanities MA had a higher number of required humanities hours. Medical humanities content in undergraduate curriculum is lower than is indicated in the AAMC annual report. Schools with a formal structure have a greater humanities presence in the curriculum and are taken by more students.


[Hip fractures in the San Pablo Hospital in 1987: descriptive study].
Hip fractures are the most disabling manifestation of osteoporosis. We reviewed all records of patients over 50 years old hospitalized with this diagnosis in San Pablo Hospital during 1987. Thirty cases were identified. The mean age of our population was higher than that reported in the literature. The mean length of stay was 16.8 days. There was a significant difference between the motor capacity of the patient prior to the precipitating event and 6 months after. The average for the in-hospital expenses was 8,826 dollars per patient. This value does not include the physician and rehabilitation costs. Mortality in the first six months was 23%. We estimate the incidence in our region at 116.5 annual cases per 100,000 persons over 50 years old.


Medication Errors and Safety Culture in a Norwegian Hospital.
Medication errors are associated with adverse health outcomes and may prolong hospital stays and increase societal costs. Safety initiatives to reduce adverse health outcomes should be based on reliable information of current shortcomings. The aim of this study was to identify barriers to medication error reporting in a hospital and to describe heath personnel's views of the safety culture. Seven interviews with health personnel (two doctors, four nurses and one pharmacist) were conducted November 2016-January 2017 at the University Hospital of North Norway. Nurses, more frequently than doctors, reported medication errors and discussed reported errors at staff meetings. Doctors preferred to solve the problem directly, for example writing a new medication order, rather than writing a report when a medication error had been identified. There was variation between the wards regarding the perception of support, confidence in and focus on error reporting, which indicates different safety cultures within the hospital. Identified barriers to medication error reporting included lack of time, and the impression that the reporting system is complicated and not user-friendly. Staff also reported inadequate training using the system, which could contribute to the perception that the system is inaccessible. Hospital management should take actions to improve the safety culture throughout the hospital based on the barriers identified in this study. This could include stronger focus on the importance of reporting medication errors, a transparent review process and clearly communicated actions.


Functional abdominal pain.
Functional abdominal pain syndrome (FAPS) is a relatively less common functional gastrointestinal (GI) disorder defined by the presence of constant or frequently recurring abdominal pain that is not associated with eating, change in bowel habits, or menstrual periods (Drossman Gastroenterology 130:1377-1390, 2006), which points to a more centrally targeted (spinal and supraspinal) basis for the symptoms. However, FAPS is frequently confused with irritable bowel syndrome and other functional GI disorders in which abdominal pain is associated with eating and bowel movements. FAPS also differs from chronic abdominal pain associated with entities such as chronic pancreatitis or chronic inflammatory bowel disease, in which the pain is associated with peripherally acting factors (eg, gut inflammation or injury). Given the central contribution to the pain experience, concomitant psychosocial disturbances are common and strongly influence the clinical expression of FAPS, which also by definition is associated with loss of daily functioning. These factors make it critical to use a biopsychosocial construct to understand and manage FAPS, because gut-directed treatments are usually not successful in managing this condition.


Genomic approaches to typing, taxonomy and evolution of bacterial isolates.
The current literature on bacterial taxonomy, typing and evolution will be critically examined from the perspective of whole-genome structure, function and organization. The following three categories of DNA band pattern studies will be reviewed: (i) random whole-genome analysis; (ii) specific gene variation and (iii) mobile genetic elements. (i) The use of RAPD, PFGE and AFLP to analyse the whole genome will provide a skeleton of polymorphic sites with exact genomic positions as whole-genome sequence data become available. (ii) Different genes provide different levels of evolutionary information for determining isolate relatedness depending on whether they are highly variable (prone to recombination events and horizontal transfer), housekeeping genes with only a small number of single nucleotide differences between isolates or part of the rrn multigene family that is prone to intragenomic recombination and concerted evolution. Comparative analyses of these different gene classes can provide enhanced information about isolate relatedness. (iii) Mobile genetic elements such as insertion sequences, transposons, plasmids and bacteriophages integrate into the bacterial genome at specific (e.g. tRNA genes) or non-specific sites to alter band patterns produced by PFGE, RAPD or AFLP. From the literature it is not clear what level of genetic element duplication constitutes non-relatedness of isolates. A model is presented that incorporates all of the above genomic characteristics for the determination of isolate relatedness in taxonomic, typing and evolutionary studies.


Requirements for DI particle prophylaxis against vesicular stomatitis virus infection in vivo.
In contrast to biologically active DI particles, neither u.v.-inactivated standard virus nor either of two different homologous u.v.-inactivated DI particles showed any prophylactic effect when injected intracerebrally into mice concomitantly challenged with VSV. Although u.v.-inactivated DI particles did not prevent death when given with the challenge virus, they did significantly lengthen the time until death occurred. Also, both u.v.-inactivated standard virus and DI particles protected mice against late challenge (at 3 or 10 days after treatment). Dosage titrations of preparations of two different active DI particles showed significant prophylaxis against simultaneous challenge with numbers of DI particles 10- to 100-fold lower than those which gave no prophylaxis when u.v.-inactivated. Thus, prophylaxis in this system in this system required biologically active DI particles.


Spanish version of the savings inventory-revised: adaptation, psychometric properties, and relationship to personality variables.
The factor structure, psychometric properties, and relationship with personality variables of a Spanish version of the Savings Inventory-Revised (SI-R) are investigated in a sample of 381 undergraduate students. A maximum likelihood factor analysis suggests a three-factor structure, which is similar but not identical to that of the original English version. The three factors mirror the three hypothesized domains of compulsive hoarding: acquisition, difficulty discarding, and clutter. The Spanish SI-R demonstrates acceptable high internal consistency and test-retest reliability, but its divergent validity is weaker than expected because of a significant overlap with depressive symptoms. Different SI-R factors are associated with different personality traits: Whereas the difficulty discarding dimension is predominantly associated with susceptibility to punishment, the acquisition dimension is predominantly associated with susceptibility to reward. The authors conclude that the Spanish SI-R is a promising instrument to measure hoarding symptoms.


Glucocorticoids modulate the mTOR pathway in the hippocampus: differential effects depending on stress history.
Glucocorticoid (GC) hormones, released by the adrenals in response to stress, are key regulators of neuronal plasticity. In the brain, the hippocampus is a major target of GC, with abundant expression of the GC receptor. GC differentially affect the hippocampal transcriptome and consequently neuronal plasticity in a subregion-specific manner, with consequences for hippocampal information flow and memory formation. Here, we show that GC directly affect the mammalian target of rapamycin (mTOR) signaling pathway, which plays a central role in translational control and has long-lasting effects on the plasticity of specific brain circuits. We demonstrate that regulators of the mTOR pathway, DNA damage-induced transcript (DDIT)4 and FK506-binding protein 51 are transcriptionally up-regulated by an acute GC challenge in the dentate gyrus (DG) subregion of the rat hippocampus, most likely via a GC-response element-driven mechanism. Furthermore, two other mTOR pathway members, the mTOR regulator DDIT4-like and the mTOR target DDIT3, are down-regulated by GC in the rat DG. Interestingly, the GC responsiveness of DDIT4 and DDIT3 was lost in animals with a recent history of chronic stress. Basal hippocampal mTOR protein levels were higher in animals exposed to chronic stress than in controls. Moreover, an acute GC challenge significantly reduced mTOR protein levels in the hippocampus of animals with a chronic stress history but not in unstressed controls. Based on these findings, we propose that direct regulation of the mTOR pathway by GC represents an important mechanism regulating neuronal plasticity in the rat DG, which changes after exposure to chronic stress.


Spatiotemporal variations of vegetation and its determinants in the National Key Ecological Function Area on Loess Plateau between 2000 and 2015.
China defined 25 National Key Ecological Function Areas in 2010 and adopted various measures to support ecosystem restoration in these areas. During the process of environment policymaking, it is important to observe the variation of vegetation and its driving factors. In this paper, we chose the National Key Ecological Function Area (NKEFA) on Loess Plateau as the study area. Based on MODIS-NDVI data between 2000 and 2015, the trend analysis was used to depict the change in NDVI and the stepwise regression analysis method was used to quantitatively assess its determinants. The results show that: (a) The vegetation coverage in study area was low in the northwest and high in the southeast, corresponding to the distribution of precipitation and temperature. (b) NDVI in the growing season increased remarkably from 0.2841 in 2000 to 0.4199 in 2015 with a linear tendency of 0.085/10a. About 71.22% of the study area experienced an extremely significant increasing of NDVI, while only 0.03% of the total area suffered from significant decreasing of NDVI. (c) Compared to climatic factors, ecosystem conservation policies, and labor transfer contributed more to the vegetation changes in the study area. In order to ensure ecological security and sustainable development in these areas, it is necessary to maintain the continuity of ecological compensation policy. Moreover, developing targeted eco-compensation policies and encouraging farmers to participate in nonfarm employment are effective ways to reach a win-win outcome of reducing the ecosystem pressure and improving the welfare of rural households.


Itaconate suppresses atherosclerosis by activating a Nrf2-dependent anti-inflammatory response in macrophages in mice.
Itaconate has emerged as a critical immunoregulatory metabolite. Here, we examined the therapeutic potential of itaconate in atherosclerosis. We found that both itaconate and the enzyme that synthesizes it, aconitate decarboxylase 1 (Acod1, also known as "immune-responsive gene 1"/IRG1) are upregulated during atherogenesis in mice. Deletion of Acod1 in myeloid cells exacerbated inflammation and atherosclerosis in vivo and resulted in an elevated frequency of a specific subset of M1-polarized proinflammatory macrophages in the atherosclerotic aorta. Importantly, Acod1 levels were inversely correlated with clinical occlusion in atherosclerotic human aorta specimens. Treating mice with the itaconate derivative 4-ocytyl itaconate attenuated inflammation and atherosclerosis induced by high cholesterol. Mechanistically, we found that the antioxidant transcription factor, Nuclear factor erythroid-2 Related Factor 2 (Nrf2) was required for itaconate to suppress macrophage activation induced by oxidized lipids in vitro and to decrease atherosclerotic lesion areas in vivo. Overall, our work shows that itaconate suppresses atherogenesis by inducing Nrf2-dependent inhibition of proinflammatory responses in macrophages. Activation of the itaconate pathway may represent an important approach to treat atherosclerosis.


Evaluation of Abstraction Capabilities and Detection of Discomfort with a Newscaster Chatbot for Entertaining Elderly Users.
We recently proposed a novel intelligent newscaster chatbot for digital inclusion. Its controlled dialogue stages (consisting of sequences of questions that are generated with hybrid Natural Language Generation techniques based on the content) support entertaining personalisation, where user interest is estimated by analysing the sentiment of his/her answers. A differential feature of our approach is its automatic and transparent monitoring of the abstraction skills of the target users. In this work we improve the chatbot by introducing enhanced monitoring metrics based on the distance of the user responses to an accurate characterisation of the news content. We then evaluate abstraction capabilities depending on user sentiment about the news and propose a Machine Learning model to detect users that experience discomfort with precision, recall, F1 and accuracy levels over 80%.


[Disturbances of heart rhythm in patients after myocardial infarction with obstructive sleep apnea during outpatient rehabilitation].
We studied specific features of heart rhythm disturbances observed during outpatient rehabilitation of 432 patients after first myocardial infarction. In 94 of these patients (21.8%) we diagnosed obstructive sleep apnea syndrome (OSAS). We noted substantial preponderance of pathologic ectopy related to OSAS with most significant detection of frequent ventricular extrasystoles. Their paired variant and polymorphic forms in patients with OSAS were 3.4 and 7.4 times, respectively, more frequent than in patients without OSAS. Frequency of ventricular ectopy rose with increase of severity of OSAS and was maximal during nocturnal hours. Analysis of correlations revealed association between OSAS and frequencies of ventricular and supraventricular extrasystoles. After myocardial infarction patients should be thoroughly examined for timely detection of OSAS and corresponding correction of their rehabilitation program.


Analysis of drug abuse among adolescent psychiatric inpatients at Veterans General Hospital-Taipei.
The problems of drug abuse has been growing rapidly in Taiwan area recently. Adolescents hospitalized due to drugs related problems were a special population and research of this population may contribute to the whole view of the drug abuse problems in our society. Psychiatric inpatient records of Veterans General Hospital-Taipei from January, 1991 to June, 1993 were reviewed. Among totally 296 admissions of 260 adolescents, 38 admissions of 27 adolescents were related to drug abuse. The discharge diagnosis, urine drug screen test during admission, hospitalization course, follow-up condition of the 38 admissions as well as the demographic data, pattern of drug abuse, family and personal problems of the 27 adolescents were collected and analyzed. Among the 27 patients, 21 (78%) abused amphetamine only or mainly, and 14 (52%) of them also drank alcohol daily. As a whole, they began to drink at age 15.6 +/- 1.5 years, to abuse amphetamine at 16.8 +/- 1.2 years. Those who sniff glue started at the age of 15.4 +/- 1.8 years and those who abuse heroin started at the age of 18 years. 14 patients (51%) had previous abstinence history, and the most common reason of failure were craving, peer pressure and boredom. Personal and family factors were the major difficulties encountered in the process of abstinence, according to the evaluation of their incharge doctors. 16 (59%) of them had definite family problems, including loss of parent(s), marital discord or inconsistent attitude of parents, and psychotic history of mother. Interestingly, 15 (56%) of the patients were the youngest, 5 (18%) were the only sons and only 3 (11%) were the eldest in their family. Among the 38 admissions, 34 (89%) were diagnosed as "organic delusional disorder", or "organic hallucinosis" by DSM-III-R criteria. Amphetamine has become one of the most popular drugs of abuse in Taiwan area in recent years. Many drugs of abuse in Taiwan area 10 years ago were not found in this study. Because of the psychidelic effect of amphetamine, many amphetamine abusers were hospitalized and the drug abusers among adolescent psychiatric inpatients have increased almost 5 times in the past 10 years. Family problems played a significant role. Family approach would thus be very important in prevention, treatment and rehabilitation of the adolescent drug abusers.


Lipids in human milk: a review. 2: Composition and fat-soluble vitamins.
Recent work on lipid classes and the fatty acid composition of milk is reviewed. At least 98% of the lipids are triacylglycerols with about 1% phospholipids and 0.3-0.4% cholesterol. Desmosterol has been identified. The major phospholipids (% of total) are: sphingomyelin (32), phosphatidylcholine (25), and phosphatidylethanolamine (28). The 12:0 content of colostrum is lower than that of mature milk. The 18:2 content of mature milk can be altered by diet; otherwise, the fatty acid composition is remarkably constant. Long-chain polyunsaturates appear to be needed for development of the infant's brain and nervous system. Data on the contents of these acids are given. The fat-soluble vitamins have been analyzed by high-performance liquid chromatography. The amounts of vitamins D and K in milk, unlike those of A and E, are lower than the quantities required to meet the U.S. Recommended Daily Allowances. Vitamin D sulfate does not appear to be a significant antirachitic component of human milk. Nutritional and analytical aspects are emphasized throughout and areas for future investigations indicated.


[Company occupational physician and work related stress: from risk assessment to health surveillance].
In Italy the recent safety legislation requires a new committment for the company occupational physician. His duty is a balance between legal requirements and the state of art of prevention. There are many tools to tackle stress at work as a general preventive intervention. The hard challenge of the company physician is to keep all the garantees in terms of prevention and social security for the worker at risk of stress. This paper examines some of the difficulties with current approaches and looks at possible solutions.


Rifaximin Prevents Intestinal Barrier Dysfunction and Alleviates Liver Injury in MCT-induced HSOS Mice.
Rifaximin is an effective component of treatment strategies for liver and intestinal diseases. However, the efficacy of rifaximin in hepatic sinusoidal obstruction syndrome (HSOS) has not been explored. The present study aimed to investigate the efficacy and mechanism of rifaximin in HSOS. An HSOS model was established in mice through the administration of monocrotaline (MCT, 800 mg/kg), and part of the HSOS mice were intragastrically administered with rifaximin. Then, the efficacy of rifaximin in HSOS was evaluated based on the liver pathological findings, liver proinflammatory cytokines, and alanine aminotransferase and aspartate aminotransferase levels. The Ussing chamber was used to evaluate the intestinal permeability, and tight junction (TJ) proteins were measured by Western blotting and real-time polymerase chain reaction to evaluate the intestinal barrier integrity. Then, the serum proinflammatory cytokine levels were evaluated by enzyme-linked immunosorbent assay. Afterwards, an in vitro experiment was performed to determine the relationship between rifaximin and TJ proteins. Rifaximin effectively alleviated the MCT-induced HSOS liver injury, suppressed the expression of liver proinflammatory cytokines, and reduced the serum levels of tumor necrosis factor-alpha and interleukin-6. Furthermore, rifaximin reduced the intestinal permeability, improved the intestinal barrier integrity, and promoted the expression of TJ proteins. The results revealed that the intestinal barrier integrity was destroyed in MCT-induced HSOS. The significant alleviation of MCT-induced HSOS induced by rifaximin might be correlated to the repairment of intestinal barrier integrity via the regulation of the TJ protein expression.


The Ars insulator facilitates I-SceI meganuclease-mediated transgenesis in the sea urchin embryo.
For the efficient generation of transgenic sea urchins, we have adopted an I-SceI meganuclease-mediated transgenesis method. Several types of promoter-GFP gene constructs flanked by two I-SceI recognition sequences were co-injected with I-SceI into sea urchin fertilized eggs. Using cell-lineage-specific promoter constructs, the frequency of transgene expression was elevated, and their level of mozaicism was reduced. The addition of the Ars insulator sequence, which is known to block the enhancer activity and protect transgenes from position effects, led to a reduction in ectopic transgene expression and an elevation of transgene expression frequency in this I-SceI-mediated system. However, the magnitude of the effects of the Ars insulator was dependent upon the promoter constructs. QPCR analysis also showed that the Ars insulator increases the transgene copy number. These results suggest that the I-SceI-mediated method using the Ars insulator is advantageous for transgenesis in the sea urchin embryo.


The effect of brown fat removal on the development of obesity in Zucker and Osborne-Mendel rats.
Removal of significant amounts of brown fat in young Zucker rats maintained at room temperature triggered compensatory changes in the remaining brown fat depots. These changes, which occurred to a greater extent in the lean than in the obese rats, enhanced the thermogenic potential of the remaining depots, thus possibly accounting for the lack of increased adiposity in these lipectomized rats. When the Zucker rats were maintained in the cold, rather than at room temperature, their ability to compensate for removal of the scapular brown fat was compromised, particularly in the obese animals. Under such conditions, the amount of functional brown fat was significantly reduced, and the amount of body fat elevated. In the lipectomized Zucker rats, this increase in adiposity was accompanied by increased body mass. In contrast, in the cold-exposed Osborne-Mendel rats, where lipectomy was not accompanied by compensatory increases in the mass and cellularity of the remaining brown fat depots, increased body fat occurred in the absence of any increase in food intake or in total body mass.


The satiety effect of disguised liquid preloads administered acutely and differing only in their nutrient content tended to be weaker for lipids but did not differ between proteins and carbohydrates in human subjects.
Whether protein is the macronutrient with the strongest satiety effect remains a matter of debate because of the diversity of study designs employed. The aim of the present study was to compare the effect of different liquid preloads made up of proteins, fats or carbohydrates only, under stringently controlled conditions, on satiety. Fifty-six subjects participated in the present study which consisted of four randomised test days, i.e. 1 d per macronutrient and one control day. During each test day, the subjects were required to consume the preload in full, and then their subsequent food intake was measured. The volunteers were divided into two groups: the first (T0) group, which consumed the preload immediately before lunch, and the second (T1) group, which consumed it 1 h beforehand. The main results showed that the participants consumed significantly less at lunch following the consumption of all three preloads than on the no-preload day, and consumed less after the consumption of the carbohydrate preload than after the consumption of the lipid preload. When energy from the preload was included, overall energy intake was significantly greater in all the three preload conditions than in the situation involving no preload, with only partial compensation for preload energy in all conditions. Total daily energy intake was highest after the lipid preload ingestion, but this could be a chance finding since it was not significantly higher than that observed after protein or carbohydrate preload ingestion. No significant effects of the interval between the preload and test meal ingestion were found. These results do not confirm the greater satiety effect of proteins than of carbohydrates, but partially confirm the weaker effect of fats.


XPC mRNA level may predict relapse in never-smokers with non-small cell lung cancers.
Disease recurrence and distant metastasis are the major causes of death in resected non-small cell lung cancer (NSCLC). The prognostic marker for never-smokers with this disease remains to be identified. To improve patient outcome, establishing an adjacent molecular marker to predict relapse of NSCLC in never-smokers is needed. Three hundred two lung tumors from NSCLC patients and normal lung tissues from 68 noncancer subjects were enrolled to evaluate XPC (xeroderma pigmentosum group C) mRNA expression by quantitative real-time reverse transcriptase polymerase chain reaction. Receiver operating characteristic curve analysis was used to search for a feasible cutoff point of XPC mRNA levels for predicting recurrence-free survival. Of the 326 patients, 214 were confirmed as only receiving surgical resection. Kaplan-Meier and multivariate Cox regression analysis were used to assess the prognostic value of XPC mRNA level in lung tumors from patients who only received surgical resection. Receiver operating characteristic curve analysis indicated 30.28 as a cutoff point, and thus 150 and 64 tumors with low- and high-XPC mRNA expression were categorized in this study population. Low-XPC mRNA appeared with more frequency in never-smokers and in late-stage (stage II-III) disease than smokers and early-stage disease (stage I). Kaplan-Meier analysis indicated that patients with low-XPC mRNA had shorter recurrence-free survival than that found in never-smokers (P = 0.002), but not in smokers (P = 0.296). Cox regression analysis further revealed that low-XPC mRNA may independently predict relapse in lung cancer of never-smokers (hazard ratio 2.34, 95% confidence interval 1.21-4.51, P = 0.011). Low-XPC mRNA may predict relapse in lung cancer patients who are never-smokers.


Prediction of 60-Day Case Fatality in Critically Ill Patients Receiving Renal Replacement Therapy: External Validation of a Prediction Model.
A recent prognostic model, predicting 60-day case fatality in critically ill patients requiring renal replacement therapy (RRT), has been developed (Acute Renal Failure Trial Network [ATN] study). Because many prognostic models are suggested in literature, but just a few have found its way into clinical practice, we aimed to externally validate this prediction model in an independent cohort. A total of 1,053 critically ill patients requiring RRT from the MIMIC-III database were analyzed. The models' discrimination was evaluated using c-statistics. Calibration was evaluated by Hosmer-Lemeshow (H-L) test and GiViTi calibration belt. In a case-mix population, including patients with normal or altered serum creatinine (sCr) at intensive care unit admission, discrimination was moderate, with a c-statistic of 0.71 in the nonintegerized risk model. In patients with altered baseline sCr, better discrimination was achieved with the integer risk model (0.76, 95% confidence interval, 0.71-0.81). As for the calibration, although the H-L test was good only in patients with normal/slightly altered sCr at admission, the calibration belt disclosed no significant deviations from the bisector line for any of the models in patients, regardless of admission sCr. Of note, a refitted model had a c-statistics of 0.85, similar to the derivation cohort. The ATN prognostic model can be useful in a broad cohort of critically ill patients. Although it showed only moderate discrimination capacity when patients with elevated admission sCr were included, using a refitted model improved it, illustrating the need for continuous external validation and updating of prognostic models over time before their implementation in clinical practice.


Pyriform sinus squamous cell carcinoma: oncological outcomes in good responders of induction chemotherapy-based larynx preservation protocols.
Induction chemotherapy-based larynx preservation protocols use chemotherapy to select exclusively patients with 'chemosensitive' tumors for a nonsurgical treatment with radiation therapy. This study on pyriform sinus squamous cell carcinoma (SCC) is interested in the oncological outcome of treatment based on radiation therapy when offered to patients with tumors responding to induction chemotherapy. This was a retrospective cohort study. The cohort included good responders to induction chemotherapy, subsequently treated with definite radiation therapy (with or without concomitant chemotherapy) for pyriform sinus SCC, in a tertiary referral cancer center. The primary endpoints were overall, laryngectomy-free and disease-free survival and the secondary endpoints were analysis of treatment failures and possibilities of salvage treatment. Forty-two patients fulfilled the inclusion criteria and were retained for analysis; 7% were stage II (3/42), 48% stage III (20/42) and 45% stage IV (19/42). At 1, 3 and 5 years, the overall survival was 95% (40/42), 74% (31/42), and 60% (SE ≈ 0.08), respectively. For the same intervals, the laryngectomy-free survival was 90% (38/42), 69% (29/42) and 50% (SE ≈ 0.08), respectively. The estimated 5-year disease-free survival was also 50%. Disease-free survival was significantly better for N0 patients. There was a 28% recurrence rate, mainly in the primary tumor site (9/11), with or without simultaneous nodal recurrence. Interestingly, more than one-third of all oncologic failures occurred beyond the first 3 years of follow-up. Salvage treatment was not possible or definitely inefficient in at least 2/3 of all recurrences. In candidates for larynx preservation for a pyriform sinus SCC, good response to induction chemotherapy followed by definite radiation therapy seems to be associated with a more favorable prognosis. Nevertheless, in case of locoregional recurrence the possibilities for efficient salvage treatment are limited.


Electron microscopic observations of reconstituted proteoliposomes with the purified major intrinsic membrane protein of eye lens fibers.
The purified major intrinsic protein of the lens fiber plasma membrane (MP26) reconstituted into liposomes favored membrane-to-membrane close contacts as visualized by freeze fracture and immunoelectron microscopy. Reconstituted apposed unilamellar vesicles formed pentalaminar profiles, and multilamellar liposomes showed regions of stacked bilayers. Immunogold labeling, using antibody directed against MP26, demonstrated that this polypeptide is present in regions of membrane-to-membrane close interaction. Fracture faces displayed both randomly distributed clusters of 8-nm polygonal intramembrane particles and membrane domains where a bidimensional lattice of repeating subunits was present. The structural pleomorphism which characterized the MP26-reconstituted proteoliposomes seems quite comparable to that visualized in natural fiber plasma membrane domains.


Assessment of dental fluorosis in Mmp20 +/- mice.
The molecular mechanisms that underlie dental fluorosis are poorly understood. The retention of enamel proteins hallmarking fluorotic enamel may result from impaired hydrolysis and/or removal of enamel proteins. Previous studies have suggested that partial inhibition of Mmp20 expression is involved in the etiology of dental fluorosis. Here we ask if mice expressing only one functional Mmp20 allele are more susceptible to fluorosis. We demonstrate that Mmp20 (+/-) mice express approximately half the amount of MMP20 as do wild-type mice. The Mmp20 heterozygous mice have normal-appearing enamel, with Vickers microhardness values similar to those of wild-type control enamel. Therefore, reduced MMP20 expression is not solely responsible for dental fluorosis. With 50-ppm-fluoride (F(-)) treatment ad libitum, the Mmp20 (+/-) mice had F(-) tissue levels similar to those of Mmp20 (+/+) mice. No significant difference in enamel hardness was observed between the F(-)-treated heterozygous and wild-type mice. Interestingly, we did find a small but significant difference in quantitative fluorescence between these two groups, which may be attributable to slightly higher protein content in the Mmp20 (+/-) mouse enamel. We conclude that MMP20 plays a nominal role in dental enamel fluorosis.


The metabolism of neuropeptides. Phase separation of synaptic membrane preparations with Triton X-114 reveals the presence of aminopeptidase N.
The property of solutions of Triton X-114 to separate into detergent-rich and detergent-poor phases at 30 degrees C has been exploited to investigate the identities of the aminopeptidases in synaptic membrane preparations from pig striatum. When titrated with an antiserum to aminopeptidase N (EC 126.96.36.199), synaptic membranes solubilized with Triton X-100 revealed that this enzyme apparently comprises no more than 5% of the activity releasing tyrosine from [Leu]enkephalin. When assayed in the presence of puromycin, this proportion increased to 20%. Three integral membrane proteins were fractionated by phase separation in Triton X-114. Aminopeptidase activity, endopeptidase-24.11 and peptidyl dipeptidase A partitioned predominantly into the detergent-rich phase when kidney microvillar membranes were so treated. However, only 5.5% of synaptic membrane aminopeptidase activity partitioned into this phase, although the other peptidases behaved predictably. About half of the aminopeptidase activity in the detergent-rich phase could now be titrated with the antiserum, showing that aminopeptidase N is an integral membrane protein of this preparation. Three aminopeptidase inhibitors were investigated for their ability to discriminate between the different activities revealed by these experiments. Although amastatin was the most potent (IC50 = 5 X 10(-7) M) it failed to discriminate between pure kidney aminopeptidase N, the total activity of solubilized synaptic membranes and that in the Triton X-114-rich phase. Bestatin was slightly more potent for total activity (IC50 = 6.3 X 10(-6) M) than for the other two forms (IC50 = 1.6 X 10(-5) M). Puromycin was a weak inhibitor, but was more selective. The activity of solubilized membranes was more sensitive (IC50 = 1.6 X 10(-5) M) than that of the pure enzyme or the Triton X-114-rich phase (IC50 = 4 X 10(-4) M). We suggest that the puromycin-sensitive aminopeptidase activity that predominates in crude synaptic membrane preparations may be a cytosolic contaminant or peripheral membrane protein rather than an integral membrane component. Aminopeptidase N may contribute to the extracellular metabolism of enkephalin and other susceptible neuropeptides in the brain.


Biplane fracture of the distal humeral lateral column: a report of two cases.
Articular fractures of the distal part of the humerus represent a challenging therapeutic problem, because they require thorough understanding of the complex local anatomy, extensile approaches, and reduction and fixation of small fragments that mainly consist of subchondral bone and articular cartilage. This report presents two cases of a unique fracture pattern of the lateral humeral column with a fracture line in the coronal plane separating the capitellum with a substantial portion of the lateral trochlear ridge, and with a second fracture line in the sagittal plane separating the residual, posterior portion of the lateral column, almost through the level of the capitellotrochlear sulcus, thus creating concomitant but distinct "low" lateral column and capitellum fractures. The radiographic findings that would suggest to the orthopaedic surgeon the possibility of this fracture pattern, the surgical approach that provides access to this complex articular fracture, and the fixation method are described.


Prediction of outcomes in patients with metabolic dysfunction-associated steatotic liver disease based on initial measurements and subsequent changes in magnetic resonance elastography.
The prognosis of metabolic dysfunction-associated steatotic liver disease (MASLD) is strongly associated with liver fibrosis. We aimed to investigate whether liver stiffness measurement (LSM) and changes in LSM (ΔLSM) on magnetic resonance elastography (MRE) can predict clinical events in patients with MASLD. We included 405 patients with MASLD who underwent at least two MREs. The patients were divided into five groups corresponding to fibrosis stages (0-4) based on initial LSM and classified as progressors (ΔLSM ≥ 19%) or non-progressors (ΔLSM < 19%) based on the difference between the first and last LSM. The mean follow-up period was 72.6 months, and the mean interval between MREs was 23.5 months. There were 52 (12.8%) progressors and 353 (87.2%) non-progressors. The initial LSM was significantly associated with the cumulative probabilities of decompensated cirrhosis, hepatocellular carcinoma (HCC), liver-related events, extrahepatic malignancies, and overall mortality but not with cardiovascular disease. Progressors had significantly higher hazard ratios (HRs) for decompensated cirrhosis, HCC, and liver-related events but not for extrahepatic malignancies, cardiovascular disease, or overall mortality. Among patients without cirrhosis, the HR for developing cirrhosis among progressors was 60.15. Progressors had a significantly higher risk of liver-related events, even in the low initial LSM (fibrosis stage 0-2) subgroups. Both initial LSM and ΔLSM can predict liver-related events in patients with MASLD, even for low initial LSM. This integrated assessment can allow more detailed risk stratification compared with single LSM assessments and identify high-risk patients with MASLD among those previously considered as low risk.


Expression signatures of DNA repair genes correlate with survival prognosis of astrocytoma patients.
Astrocytomas are the most common primary brain tumors. They are very resistant to therapies and usually progress rapidly to high-grade lesions. Here, we investigated the potential role of DNA repair genes in astrocytoma progression and resistance. To this aim, we performed a polymerase chain reaction array-based analysis focused on DNA repair genes and searched for correlations between expression patters and survival prognoses. We found 19 genes significantly altered. Combining these genes in all possible arrangements, we found 421 expression signatures strongly associated with poor survival. Importantly, five genes (DDB2, EXO1, NEIL3, BRCA2, and BRIP1) were independently correlated with worse prognoses, revealing single-gene signatures. Moreover, silencing of EXO1, which is remarkably overexpressed, promoted faster restoration of double-strand breaks, while NEIL3 knockdown, also highly overexpressed, caused an increment in DNA damage and cell death after irradiation of glioblastoma cells. These results disclose the importance of DNA repair pathways for the maintenance of genomic stability of high-grade astrocytomas and suggest that EXO1 and NEIL3 overexpression confers more efficiency for double-strand break repair and resistance to reactive oxygen species, respectively. Thereby, we highlight these two genes as potentially related with tumor aggressiveness and promising candidates as novel therapeutic targets.


The transcriptional activation and repression domains of RFX1, a context-dependent regulator, can mutually neutralize their activities.
EP is a DNA element found in regulatory regions of viral and cellular genes. While being a key functional element in viral enhancers, EP has no intrinsic enhancer activity but can stimulate or silence transcription in a context-dependent manner. The EP element is bound by RFX1, which belongs to a novel, evolutionarily conserved protein family. In an attempt to decipher the mechanism by which EP regulates transcription, the intrinsic transcriptional activity of RFX1 was investigated. A functional dissection of RFX1, by analysis of deletion mutants and chimeric proteins, identified several regions with independent transcriptional activity. An activation domain containing a glutamine-rich region is found in the N-terminal half of RFX1, while a region with repressor activity overlaps the C-terminal dimerization domain. In RFX1 these activities were mutually neutralized, producing a nearly inactive transcription factor. This neutralization effect was reproduced by fusing RFX1 sequences to a heterologous DNA-binding domain. We propose that relief of self-neutralization may allow RFX1 to act as a dual-function regulator via its activation and repression domains, accounting for the context-dependent activity of EP.


Targeting the Wnt/β-catenin signaling pathway in human cancers.
The Wnt/β-catenin signaling pathway plays a pivotal role in the regulation of cell growth, cell development and the differentiation of normal stem cells. Constitutive activation of the Wnt/β-catenin signaling pathway is found in many human cancers, and is thus an attractive target for anti-cancer therapy. Specific inhibitors of this pathway have been keenly researched and developed. This review discusses the potential of inhibiting the Wnt/β-catenin signaling pathway, as a therapeutic approach for cancer, along with an overview of the development of specific inhibitors. Cancer stem cells (CSCs) play a significant role in the development and recurrence of several cancers, and Wnt/β-catenin signaling is important for the proliferation of CSCs. Inhibition of Wnt/β-catenin signaling is therefore a promising treatment approach. Progress has been made in the development of screening methods to identify Wnt/β-catenin signaling inhibitors. Biomarker-based screening is an effective and promising method for the identification of compounds of interest.


Technology in the teaching of neuroscience: enhanced student learning.
The primary motivation for integrating any form of education technology into a particular course or curriculum should always be to enhance student learning. However, it can be difficult to determine which technologies will be the most appropriate and effective teaching tools. Through the alignment of technology-enhanced learning experiences with a clear set of learning objectives, teaching becomes more efficient and effective and learning is truly enhanced. In this article, I describe how I have made extensive use of technology in two neuroscience courses that differ in structure and content. Course websites function as resource centers and provide a forum for student interaction. PowerPoint presentations enhance formal lectures and provide an organized outline of presented material. Some lectures are also supplemented with interactive CD-ROMs, used in the presentation of difficult physiological concepts. In addition, a computer-based physiological recording system is used in laboratory sessions, improving the hands-on experience of group learning while reinforcing the concepts of the research method. Although technology can provide powerful teaching tools, the enhancement of the learning environment is still dependent on the instructor. It is the skill and enthusiasm of the instructor that determines whether technology will be used effectively.


Impact of postoperative complications on hospital costs following the Norwood operation.
Introduction Patients undergoing the Norwood operation consume considerable healthcare resources; however, detailed information regarding factors impacting hospitalisation costs is lacking. We evaluated the association of postoperative complications with hospital costs. In the present study, we utilised a unique data set consisting of prospectively collected clinical data from the Pediatric Heart Network Single Ventricle Reconstruction trial linked at the patient level with cost data for 10 hospitals participating in the Children's Hospital Association Case Mix database during the trial period. The relationship between complications and cost was modelled using linear regression, accounting for the skewed distribution of cost, adjusting for within-centre clustering and baseline patient characteristics. A total of 334 eligible Norwood records (97.5%) were matched between data sets. Overall, 82% suffered from at least one complication (median 2; with a range from 0 to 33). Those with complications had longer postoperative length of stay (25 versus 12 days, p<0.001), more total ventilator days (7 versus 5 days, p<0.001), and higher in-hospital mortality (17.6 versus 3.4%, p<0.006). Mean adjusted hospital cost in those with a complication was $190,689 (95% CI $111,344-$326,577) versus $120,584 (95% CI $69,246-$209,983) in those without complications (p=0.002). Costs increased with the number of complications (1-2 complications=$132,800 versus 3-4 complications=$182,353 versus ⩾5 complications=$309,372 [p<0.001]). This merged data set of clinical trial and cost data demonstrated that postoperative complications are common following the Norwood operation and are associated with worse clinical outcomes and higher costs. Efforts to reduce complications in this population may lead to improved outcomes and cost savings.


Genome-wide identification and expression profiling of the C2H2-type zinc finger protein transcription factor family in tobacco.
C2H2 zinc finger protein transcription factor family members have important biological functions in eukaryotes. They not only bind DNA and RNA, but also interact with proteins. In this study, 118 members of the tobacco C2H2 zinc finger protein transcription factor family were identified from the N. tabacum genome database by using Pfam, SMART and Blastp. The analyses of phylogenetic tree, physical and chemical properties, chromosomal mapping, gene structures, protein three-dimensional structures and tissue expression patterns were performed. The results suggested that the peptide length of different subfamily members is significantly different. Phylogenetic and motif analysis revealed that the C2H2 zinc finger protein transcription factor family members can be divided into 5 subfamilies and each member has at least one C2H2 motif. Genes of the family members are distributed across the 22 chromosomes. C2H2 zinc finger protein transcription factor family members are expressed in different tissues although some have higher expression levels in leaves and roots. This study will be helpful for further analysis of the C2H2 zinc finger family proteins in other plants.