The effect of short-term increase of estradiol levels on sexual desire and orgasm frequency in women and men: A double-blind, randomized, placebo-controlled trial.
Estradiol (E2) has been implicated in sexual functioning in both sexes. E2 levels change distinctively over the menstrual cycle, peaking around ovulation. Data on short-term effects of fluctuating E2 levels on sexual desire are however sparse and mostly based on observational studies. To fill this gap, we ran a double-blind, randomized, placebo-controlled study (N = 126) to investigate the effects of a short-term increase in E2 on sexual desire and orgasm frequency in healthy, young men and women. Circulating E2 levels were elevated through estradiol valerate (E2V) administered over two consecutive days to simulate the rise in E2 levels around ovulation. E2V had no effect on orgasm frequency and only minor effects on sexual desire. On average, the administered E2V dampened change in sexual desire compared to untreated participants with comparable baseline sexual desire in such a way that sexual desire was slightly reduced even in those with higher baseline sexual desire. These findings suggest that short-term increases in E2 have little effect on sexual function and are unlikely to explain the increase in sexual desire around ovulation.


Oxidative stress and neurobehavioral problems in pediatric acute lymphoblastic leukemia patients undergoing chemotherapy.
Neurobehavioral problems after chemotherapy treatment for pediatric acute lymphoblastic leukemia (ALL) have been a recent focus of investigation. This study extended previous research that suggested oxidative stress as a potential mechanism for chemotherapy-induced central nervous system injury by examining early markers of oxidative stress in relation to subsequent neurobehavioral problems. Oxidized and unoxidized components of phosphatidylcholine (PC) were measured in the cerebrospinal fluid of 87 children with ALL at diagnosis, induction, and consolidation. Behavioral assessments were conducted postconsolidation and at the end of chemotherapy. Results revealed a significant association between physiologic reactivity (high vs. low PC changes from diagnosis) and behavioral outcomes (high vs. low pathology). Elevated oxidized PC fraction change was predictive of increased problems with aggression at the end of therapy as well as postconsolidation adaptability. Furthermore, symptoms of hyperactivity systematically changed over time in relation to both unoxidized PC and oxidized PC fraction reactivity. These findings suggest that symptoms of behavioral problems occur early in the course of chemotherapy and that increases in the cerebrospinal fluid PC markers of oxidative stress during induction and consolidation may help to predict certain future behavioral problems.


A critical analysis of the impacts of COVID-19 on the global economy and ecosystems and opportunities for circular economy strategies.
The World Health Organization declared COVID-19 a global pandemic on the 11th of March 2020, but the world is still reeling from its aftermath. Originating from China, cases quickly spread across the globe, prompting the implementation of stringent measures by world governments in efforts to isolate cases and limit the transmission rate of the virus. These measures have however shattered the core sustaining pillars of the modern world economies as global trade and cooperation succumbed to nationalist focus and competition for scarce supplies. Against this backdrop, this paper presents a critical review of the catalogue of negative and positive impacts of the pandemic and proffers perspectives on how it can be leveraged to steer towards a better, more resilient low-carbon economy. The paper diagnosed the danger of relying on pandemic-driven benefits to achieving sustainable development goals and emphasizes a need for a decisive, fundamental structural change to the dynamics of how we live. It argues for a rethink of the present global economic growth model, shaped by a linear economy system and sustained by profiteering and energy-gulping manufacturing processes, in favour of a more sustainable model recalibrated on circular economy (CE) framework. Building on evidence in support of CE as a vehicle for balancing the complex equation of accomplishing profit with minimal environmental harms, the paper outlines concrete sector-specific recommendations on CE-related solutions as a catalyst for the global economic growth and development in a resilient post-COVID-19 world.


Administration of Tauroursodeoxycholic Acid Attenuates Early Brain Injury via Akt Pathway Activation.
Traumatic brain injury (TBI) is one of the leading causes of trauma-induced mortality and disability, and emerging studies have shown that endoplasmic reticulum (ER) stress plays an important role in the pathophysiology of TBI. Tauroursodeoxycholic acid (TUDCA), a hydrophilic bile acid, has been reported to act as an ER stress inhibitor and chemical chaperone and to have the potential to attenuate apoptosis and inflammation. To study the effects of TUDCA on brain injury, we subjected mice to TBI with a controlled cortical impact (CCI) device. Using western blotting, we first examined TBI-induced changes in the expression levels of GRP78, an ER stress marker, p-PERK, PERK, p-eIF2a, eIF2a, ATF4, p-Akt, Akt, Pten, Bax, Bcl-2, Caspase-12 and CHOP, as well as changes in the mRNA levels of Akt, GRP78, Caspase-12 and CHOP using RT-PCR. Neuronal cell death was assessed by a terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end-labeling (TUNEL) assay, and CHOP expression in neuronal cells was detected by double-immunofluorescence staining. Neurological and motor deficits were assessed by modified neurological severity scores (mNSS) and beam balance and beam walking tests, and brain water content was also assessed. Our results indicated that ER stress peaked at 72 h after TBI and that TUDCA abolished ER stress and inhibited p-PERK, p-eIF2a, ATF4, Pten, Caspase-12 and CHOP expression levels. Moreover, our results show that TUDCA also improved neurological function and alleviated brain oedema. Additionally, TUDCA increased p-Akt expression and the Bcl-2/Bax ratio. However, the administration of the Akt inhibitor MK2206 or siRNA targeting of Akt abolished the beneficial effects of TUDCA. Taken together, our results indicate that TUDCA may attenuate early brain injury via Akt pathway activation.


Roots, nitrogen transformations, and ecosystem services.
This review considers some of the mechanistic processes that involve roots in the soil nitrogen (N) cycle, and their implications for the ecological functions that retain N within ecosystems: 1) root signaling pathways for N transport systems, and feedback inhibition, especially for NO(3)(-) uptake; 2) dependence on the mycorrhizal and Rhizobium/legume symbioses and their tradeoffs for N acquisition; 3) soil factors that influence the supply of NH(4)(+) and NO(3)(-) to roots and soil microbes; and 4) rhizosphere processes that increase N cycling and retention, such as priming effects and interactions with the soil food web. By integrating information on these plant-microbe-soil N processes across scales and disciplinary boundaries, we propose ideas for better manipulating ecological functions and processes by which the environment provides for human needs, i.e., ecosystem services. Emphasis is placed on agricultural systems, effects of N deposition in natural ecosystems, and ecosystem responses to elevated CO(2) concentrations. This shows the need for multiscale approaches to increase human dependence on a biologically based N supply.


Emergency preparedness: What do new college students need to know and how do you inform them?
Active shooters, tornadoes, fires, floods, and power outages are concerns for every new student entering college. New students enter college with a variety of academic and nonacademic anxieties. Students express concerns of their study skills, as well as their ability to manage financial and social responsibilities, but seldom does a new student worry about personal safety or disasters. The first few minutes of an emergency can mean the difference between life and death. Candlelight vigils showing incredible sorrow among college students may become more frequent as active shooter incidents continue to increase in frequency and will undoubtedly occur again. The question is: What do new students need to know about emergency preparedness and how do you inform them? Information overload combined with new student mindset of invincibility makes emergency preparedness a tough topic to communicate effectively to new students. University officials owe it to new students to try.


Pneumocephaly from epidural anesthesia.
An elderly woman who had spinal epidural anesthesia thereafter had headache, anorexia, nausea and vomiting, dehydration, seizures, and cardiovascular collapse. CAT scan revealed air in the posterior fossa, probably caused by intradural injection of air during epidural anesthesia. We propose that this may be an occasional cause of headache or more substantial complications after epidural anesthesia, and suggest that CAT scanning may be helpful in identifying this complication.


Fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs) and nonallergic food intolerance: FODMAPs or food chemicals?
Food intolerance in irritable bowel syndrome (IBS) is increasingly being recognized, with patients convinced that diet plays a role in symptom induction. Evidence is building to implicate fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs) in the onset of abdominal pain, bloating, wind and altered bowel habit through their fermentation and osmotic effects. Hypersensitivity to normal levels of luminal distension is known to occur in patients with IBS, with consideration of food chemical intolerance likely to answer many questions about this physiological process. This paper summarizes the evidence and application of the most common approaches to managing food intolerance in IBS: the low-FODMAP diet, the elimination diet for food chemical sensitivity and others including possible noncoeliac gluten intolerance.


A national, multicentre, web-based point prevalence survey of antimicrobial use and quality indices among hospitalised paediatric patients across South Africa.
Data on antimicrobial consumption among the paediatric population in public hospitals in South Africa are limited. This needs to be addressed to improve future antimicrobial use and reduce antimicrobial resistance rates. This study aimed to quantify antimicrobial usage and to identify and classify which antimicrobials are used in the paediatric population in public sector hospitals in South Africa according to the World Health Organization (WHO) AWaRe list of antimicrobials. A point prevalence survey was conducted among 18 public sector hospitals from nine provinces using a newly developed web-based application. Data were analysed according to the WHO AWaRe list to guide future quality improvement programmes. A total of 1261 paediatric patient files were reviewed, with 49.7% (627/1261) receiving at least one antimicrobial and with 1013 antimicrobial prescriptions overall. The top five antimicrobials included ampicillin (16.4%), gentamicin (10.0%), amoxicillin/enzyme inhibitor (9.6%), ceftriaxone (7.4%) and amikacin (6.3%). Antimicrobials from the 'Access' classification were the most used (55.9%), with only 3.1% being from the 'Reserve' classification. The most common infectious conditions for which an antimicrobial was prescribed were pneumonia (14.6%; 148/1013) and clinical sepsis (11.0%; 111/1013). Parenteral administration (75.6%; 766/1013) and prolonged surgical prophylaxis (66.7%; 10/15) were common concerns. Only 28.0% (284/1013) of prescribed antimicrobials had cultures requested; of which only 38.7% (110/284) of culture results were available in the files. Overall, antimicrobial prescribing is common among paediatric patients in South Africa. Interventions should be targeted at improving antimicrobial prescribing, including surgical prophylaxis, and encouraging greater use of oral antibiotics.


Phase conversion from hexagonal CuS(y)Se(1-y) to cubic Cu(2-x)S(y)Se(1-y): composition variation, morphology evolution, optical tuning, and solar cell applications.
In this work, we report a simple and low-temperature approach for the controllable synthesis of ternary Cu-S-Se alloys featuring tunable crystal structures, compositions, morphologies, and optical properties. Hexagonal CuS(y)Se(1-y) nanoplates and face centered cubic (fcc) Cu(2-x)S(y)Se(1-y) single-crystal-like stacked nanoplate assemblies are synthesized, and their phase conversion mechanism is well investigated. It is found that both copper content and chalcogen composition (S/Se atomic ratio) of the Cu-S-Se alloys are tunable during the phase conversion process. Formation of the unique single-crystal-like stacked nanoplate assemblies is resulted from oriented stacking coupled with the Ostwald ripening effect. Remarkably, optical tuning for continuous red shifts of both the band-gap absorption and the near-infrared localized surface plasmon resonance are achieved. Furthermore, the novel Cu-S-Se alloys are utilized for the first time as highly efficient counter electrodes (CEs) in quantum dot sensitized solar cells (QDSSCs), showing outstanding electrocatalytic activity for polysulfide electrolyte regeneration and yielding a 135% enhancement in power conversion efficiency (PCE) as compared to the noble metal Pt counter electrode.


Sonochemical synthesis of iron-graphene oxide/honeycomb-like ZnO ternary nanohybrids for sensitive electrochemical detection of antipsychotic drug chlorpromazine.
We report a novel electrochemical sensor for the sensitive and selective determination of the antipsychotic drug chlorpromazine (CPZ) based on the iron (Fe) nanoparticles-loaded graphene oxide (GO-Fe)/three dimensional (3D) honeycomb-like zinc oxide (ZnO) nanohybrid modified screen printed carbon electrode (SPCE). The 3D hierarchical honeycomb-like ZnO was synthesized using a novel aqueous hydrothermal method and the GO-Fe/ZnO nanohybrid was prepared based on an inexpensive and fast sonochemical method using a high-intensity ultrasonic bath (Delta DC200H, 200 W, 40 KHz). Characterizations including scanning electron microscopy, elemental mapping, transmission electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy, and Raman spectroscopy were carried out as part of this work. The electrocatalytic oxidation behavior of CPZ at various electrodes was investigated using the cyclic voltammetry technique, through which the GO-Fe/ZnO modified SPCE was identified as the best performing electrode. The quantitative determination of CPZ was then performed using the differential pulse voltammetry technique. The as-prepared GO-Fe/ZnO/SPCE sensor exhibited a quick and sensitive response towards the oxidation of CPZ with linear concentration ranges from 0.02 to 172.74 μM and 222.48 to 1047.74 μM. The modified SPCE sensor displayed a low detection limit (LOD) of 0.02 µM and a high sensitivity of 7.56 µA µM-1 cm-2. The proposed sensor also showed remarkable operational and storage stability, reproducibility, and repeatability. Furthermore, the practicability of the GO-Fe/ZnO/SPCE sensor has been verified with real sample analysis using commercial antipsychotic CPZ tablets and human urine samples, and adequate recovery has been achieved.


Musculoskeletal Imaging Findings of Hematologic Malignancies.
Hematologic malignancies comprise a set of prevalent yet clinically diverse diseases that can affect every organ system. Because blood components originate in bone marrow, it is no surprise that bone marrow is a common location for both primary and metastatic hematologic neoplasms. Findings of hematologic malignancy can be seen with most imaging modalities including radiography, computed tomography (CT), technetium 99m (99mTc) methylene diphosphonate (MDP) bone scanning, fluorine 18 (18F) fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT, and magnetic resonance (MR) imaging. Because of the diversity of imaging appearances and clinical behavior of this spectrum of disease, diagnosis can be challenging, and profound understanding of the underlying pathophysiologic changes and current treatment modalities can be daunting. The appearance of normal bone marrow at MR imaging and FDG PET/CT is also varied due to dynamic compositional changes with normal aging and in response to hematologic demand or treatment, which can lead to false-positive interpretation of imaging studies. In this article, the authors review the normal maturation and imaging appearance of bone marrow. Focusing on lymphoma, leukemia, and multiple myeloma, they present the spectrum of imaging findings of hematologic malignancy affecting the musculoskeletal system and the current imaging tools available to the radiologist. They discuss the imaging findings of posttreatment bone marrow and review commonly used staging systems and consensus recommendations for appropriate imaging for staging, management, and assessment of clinical remission. ©RSNA, 2017.


Emotional intelligence and social functioning in persons with schizotypy.
The present study is the first to examine emotional intelligence in persons with schizotypy. Over 2100 undergraduates were screened for schizotypy with the Schizotypal Personality Questionnaire-Brief Version. Forty participants identified as persons with high schizotypy and 56 participants identified as persons with low schizotypy completed assessments of emotional intelligence (Mayer-Salovey-Caruso Emotional Intelligence Test), social functioning (Social Adjustment Scale-Self Report), verbal episodic (secondary) memory (California Verbal Learning Test), and executive functioning (Wisconsin Card Sorting Test). Persons high in schizotypy were impaired in overall emotional intelligence and two aspects of emotional intelligence, the ability to perceive emotions and the ability to manage emotions. Persons high in schizotypy were also impaired in three aspects of social functioning: peer relationships, family relationships, and academic functioning. Group differences in verbal episodic (secondary) memory and executive functioning were not observed. For persons with high schizotypy, overall emotional intelligence and two aspects of emotional intelligence, the ability to perceive emotions and the ability to manage emotions, were associated with peer relationship functioning. Overall emotional intelligence was associated with verbal episodic (secondary) memory, but not executive functioning, in persons with high schizotypy. The current findings suggest that emotional intelligence is impaired in persons with schizotypy and that these impairments affect their social functioning.


The role of p53 in treatment responses of lung cancer.
Resistance to radio- and chemotherapy is a major problem in treatment responses of lung cancer. In this disease, biological markers, that can be predictive of response to treatment for guiding clinical practice, still need to be validated. Radiotherapy and most chemotherapeutic agents directly target DNA and in response to such therapies, p53 functions as a coordinator of the DNA repair process, cell cycle arrest, and apoptosis. In fact, it participates in the main DNA repair systems operative in cells, including NHEJ, HRR, NER, BER, and MMR. Given the high p53 mutation frequency in lung cancer which likely impairs some of the p53-mediated functions, a role of p53 as a predictive marker for treatment responses has been suggested. In this review, we summarize the conflicting results coming from preclinical and clinical studies on the role of p53 as a predictive marker of responses to chemotherapy or radiotherapy in lung cancer.


Neuroblast migration along cellular substrates in the developing porcine brain.
In the past decade it has become evident that neuroblasts continue to supply the human cortex with interneurons via unique migratory streams shortly following birth. Owing to the size of the human brain, these newborn neurons must migrate long distances through complex cellular landscapes to reach their final locations. This process is poorly understood, largely because of technical difficulties in acquiring and studying neurotypical postmortem human samples along with diverging developmental features of well-studied mouse models. We reasoned that migratory streams of neuroblasts utilize cellular substrates, such as blood vessels, to guide their trek from the subventricular zone to distant cortical targets. Here, we evaluate the association between young interneuronal migratory streams and their preferred cellular substrates in gyrencephalic piglets during the developmental equivalent of human birth, infancy, and toddlerhood.


Incidence Estimates of Acute Q Fever and Spotted Fever Group Rickettsioses, Kilimanjaro, Tanzania, from 2007 to 2008 and from 2012 to 2014.
Q fever and spotted fever group rickettsioses (SFGR) are common causes of severe febrile illness in northern Tanzania. Incidence estimates are needed to characterize the disease burden. Using hybrid surveillance-coupling case-finding at two referral hospitals and healthcare utilization data-we estimated the incidences of acute Q fever and SFGR in Moshi, Kilimanjaro, Tanzania, from 2007 to 2008 and from 2012 to 2014. Cases were defined as fever and a four-fold or greater increase in antibody titers of acute and convalescent paired sera according to the indirect immunofluorescence assay of Coxiella burnetii phase II antigen for acute Q fever and Rickettsia conorii (2007-2008) or Rickettsia africae (2012-2014) antigens for SFGR. Healthcare utilization data were used to adjust for underascertainment of cases by sentinel surveillance. For 2007 to 2008, among 589 febrile participants, 16 (4.7%) of 344 and 27 (8.8%) of 307 participants with paired serology had Q fever and SFGR, respectively. Adjusted annual incidence estimates of Q fever and SFGR were 80 (uncertainty range, 20-454) and 147 (uncertainty range, 52-645) per 100,000 persons, respectively. For 2012 to 2014, among 1,114 febrile participants, 52 (8.1%) and 57 (8.9%) of 641 participants with paired serology had Q fever and SFGR, respectively. Adjusted annual incidence estimates of Q fever and SFGR were 56 (uncertainty range, 24-163) and 75 (uncertainty range, 34-176) per 100,000 persons, respectively. We found substantial incidences of acute Q fever and SFGR in northern Tanzania during both study periods. To our knowledge, these are the first incidence estimates of either disease in sub-Saharan Africa. Our findings suggest that control measures for these infections warrant consideration.


GC-MS quantification of urinary symmetric dimethylarginine (SDMA), a whole-body symmetric l-arginine methylation index.
Circulating and excretory NG,N´G-dimethyl-l-arginine (symmetric dimethylarginine, SDMA) and NG,NG-dimethyl-l-arginine (asymmetric dimethylarginine, ADMA) are cardiovascular risk factors. Despite close chemical structures, the gas chromatography-mass spectrometry (GC-MS) measurement of SDMA is remarkably more difficult than that of ADMA for as yet unknown reasons. Here, we describe an improved GC-MS method for the quantitative determination of SDMA in human urine using commercially available NG,N´G-di-[2H3]methyl-l-arginine (d6-SDMA) as internal standard. The method is based on a single derivatization step with pentafluoropropionic anhydride (PFPA) in ethyl acetate (30 min, 65 °C) to N,N,N,O-tetrakis-pentafluoropropionyl derivatives, electron-capture negative-ion chemical ionization and selected-ion monitoring of the mass-to-charge (m/z) ions of m/z 456 for SDMA and m/z 462 for d6-SDMA.


Autonomous multielectrode system for monitoring the interactions of isoflavonoids with lung cancer cells.
The cytotoxic effect of isoflavonoids in the development of different forms of cancer has been reported by epidemiological and dietary studies. Consequently, there is a search for an accurate and reliable method for monitoring the interactions of these chemicals with cancerous cells. We have developed and optimized a fully autonomous electrochemical biosensor for studying the role of isoflavonoids on A549 lung adenocarcinoma cell line. This advanced biosensor uses a prototype 96-electrode (DOX-96) well-type device that allows the measurement of cell respiratory activity via the consumption of dissolved oxygen. The system provides a continuous, real-time monitoring of cell activity upon exposure to naturally occurring polyphenols, specifically resveratrol, genistein, and quercetin. The system is equipped with a multipotentiostat, a 96-electrode well for measurements and cell culturing with 3 disposable electrodes fitted into each well. A comparison with classical "cell culture" techniques indicates that the biosensor provides real-time measurement with no added reagents. A detection limit of 1 x 10(4) was recorded versus 200 and 6 x 10(3) cells/well for MTT and fluorescence assays, respectively. This method was optimized with respect to cell stability, reproducibility, applied potential, cell density per well, volume/composition of cell culture medium per well, and incubation. Others include total measuring time, temperature, and sterilization procedure. This study represents a basic research tool that may allow researchers to study the type, level, and specific influence of isoflavonoids on cells.


The hearing gene Prestin reunites echolocating bats.
The remarkable high-frequency sensitivity and selectivity of the mammalian auditory system has been attributed to the evolution of mechanical amplification, in which sound waves are amplified by outer hair cells in the cochlea. This process is driven by the recently discovered protein prestin, encoded by the gene Prestin. Echolocating bats use ultrasound for orientation and hunting and possess the highest frequency hearing of all mammals. To test for the involvement of Prestin in the evolution of bat echolocation, we sequenced the coding region in echolocating and nonecholocating species. The resulting putative gene tree showed strong support for a monophyletic assemblage of echolocating species, conflicting with the species phylogeny in which echolocators are paraphyletic. We reject the possibilities that this conflict arises from either gene duplication and loss or relaxed selection in nonecholocating fruit bats. Instead, we hypothesize that the putative gene tree reflects convergence at stretches of functional importance. Convergence is supported by the recovery of the species tree from alignments of hydrophobic transmembrane domains, and the putative gene tree from the intra- and extracellular domains. We also found evidence that Prestin has undergone Darwinian selection associated with the evolution of specialized constant-frequency echolocation, which is characterized by sharp auditory tuning. Our study of a hearing gene in bats strongly implicates Prestin in the evolution of echolocation, and suggests independent evolution of high-frequency hearing in bats. These results highlight the potential problems of extracting phylogenetic signals from functional genes that may be prone to convergence.


Leading a supply chain turnaround.
Just five years ago, salespeople at Whirlpool were in the habit of referring to their supply chain organization as the "sales disablers." Now the company excels at getting products to the right place at the right time--while managing to keep inventories low. How did that happen? In this first-person account, Reuben Slone, Whirlpool's vice president of Global Supply Chain, describes how he and his colleagues devised the right supply chain strategy, sold it internally, and implemented it. Slone insisted that the right focal point for the strategy was the satisfaction of consumers at the end of the supply chain. Most supply chain initiatives do the opposite: They start with the realities of a company's manufacturing base and proceed from there. Through a series of interviews with trade customers large and small, his team identified 27 different capabilities that drove industry perceptions of Whirlpool's performance. Knowing it was infeasible to aim for world-class performance across all of them, Slone weighed the costs of excelling at each and found the combination of initiatives that would provide overall competitive advantage. A highly disciplined project management office and broad training in project management were key to keeping work on budget and on benefit. Slone set an intense pace--three "releases" of new capabilities every month--that the group maintains to this day. Lest this seem like a technology story, however, Slone insists it is just as much a "talent renaissance." People are proud today to be part of Whirlpool's supply chain organization, and its new generation of talent will give the company a competitive advantage for years to come.


Review article: cytomegalovirus and inflammatory bowel disease.
The association between ulcerative colitis and cytomegalovirus (CMV) has been recognised for over 50 years; and the role of CMV in ulcerative colitis in general, and steroid resistance in particular, remains a topic of ongoing controversy. The outcome for patients with CMV reactivation appears worse than that for patients without reactivation, but it is not entirely clear whether CMV is a contributor or a bystander and if treatment with anti-virals alters the course of inflammatory bowel disease (IBD). To review the role of CMV associated with IBD, including epidemiology, clinical features, diagnosis and management strategies. By reviewing literature available on CMV associated with IBD in adult patients. A PubMed literature search was performed using the following terms individually or in combination: CMV colitis, cytomegalovirus colitis, IBD and CMV, CMV treatment. Cytomegalovirus reactivation is common in patients with severe colitis, with a reported prevalence of 4.5-16.6%, and as high as 25% in patients requiring colectomy for severe colitis. The outcome for this group of patients appears worse than that for patients without reactivation; however, reported remission rates following treatment with anti-viral therapy are as high as 71-86%. Evidence, although not conclusive, supports testing for CMV colonic disease in cases of moderate to severe colitis, by processing biopsies for haematoxylin and eosin staining with immunohistochemistry and/or, CMV DNA real-time polymerase chain reaction; and if present treating with ganciclovir.


Can Intraoperative Video Recordings Contribute to Improving Laparoscopic Percutaneous Extraperitoneal Closure in Children with Inguinal Hernia and Prevent Recurrence? A Pilot Study.
Aim: We reviewed intraoperative video recordings (IVRs) of laparoscopic percutaneous extraperitoneal closure (LPEC) for inguinal hernia in children blindly to assess performance. Methods: IVRs of 183 LPEC performed between April 2013 and March 2016, graded by the operating surgeon as difficult (D; n = 8), straightforward (S; n = 96), or easy (E; n = 79), were scored by a panel of reviewers with advanced (group A; >400 LPEC cases; n = 5), intermediate (group I; 50-150 cases; n = 5), and basic (group B; <10 cases; n = 5) experience, according to suturing, dissection plane, vas/vessel dissection, bleeding, and peritoneal injury. They also allocated a recurrence risk rank (RRR; highest = 6; lowest = 1) for each IVR. Mean score variance for each IVR was also compared between reviewers. Results: There was one recurrence (R; 4-year-old male; level E). RRR were: 1, 2, and 2 for reviewers A, I, and B, respectively. Reviewer A scores for "suturing" and "bleeding," and reviewer I scores for "dissection plane" and "peritoneal injury" correlated significantly with RRR. No reviewer B scores correlated with RRR. Score variance between A and I and A and B for cases D1 and D2 were statistically significant. Conclusion: Advanced reviewers showed greatest variance, questioning the validity of whether experience alone improves surgical technique.


Magnetic cortical oscillations associated with subjective auditory coolness during paired comparison of time-varying HVAC sounds.
The impressions of heating, ventilation, and air conditioning (HVAC) sounds are important for the comfort people experience in their living spaces. Revealing neural substrates of the impressions induced by HVAC sounds can help to develop neurophysiological indices of the comfort of HVAC sounds. There have been numerous studies on the brain activities associated with the pleasantness of sounds, but few on the brain activities associated with the thermal impressions of HVAC sounds. Seven time-varying HVAC sounds were synthesized as stimuli using amplitude modulation. Six participants took part in subjective evaluation tests and MEG measurements. Subjective coolness of the HVAC sounds was measured using the paired comparison method. Magnetoencephalographic (MEG) measurements were carried out while participants listened to and compared the time-varying HVAC sounds. Time-frequency analysis and cluster-based analysis were performed on the MEG data. The subjective evaluation tests showed that the subjective coolness of the amplitude-modulated HVAC sounds was affected by the modulation frequency, and that there was individual difference in subjective coolness. A cluster-based analysis of the MEG data revealed that the brain activities of two participants significantly differed when they listened to cooler or less cool HVAC sounds. The frontal low-theta (4-5 Hz) and the temporal alpha (8-13 Hz) activities were observed. The frontal low-theta and the temporal alpha activities may be associated with the coolness of HVAC sound. This result suggests that the comfort level of HVAC sound can be evaluated and individually designed using neurophysiological measurements.


Growth of Pseudomonas aeruginosa on nitrous oxide.
Three strains of Pseudomonas aeruginosa were grown anaerobically on exogenous N2O in a defined medium under conditions that assured the maintenance of highly anaerobic conditions for periods of 1 week or more. The bacteria were observed reproducibly to increase their cell density by factors of 3 to 9, but not more, depending on the initial amount of N2O. Growth on N2O was cleanly blocked by acetylene. Cell yields, CO2 production, and N2O uptake all increased with initial PN2O at PN2O less than or equal to 0.1 atm. Growth curves were atypical in the sense that growth rates decreased with time. This is the first observation of growth of P. aeruginosa on N2O as the sole oxidant. N2O was shown to be an obligatory, freely diffusible intermediate during growth of strains PAO1 and P1 on nitrate. All three strains used this endogenous N2O efficiently for growth. For strains PAO1 and P1, it was confirmed that exogenous N2O had little effect on the cell yields of cultures growing with nitrate; thus, for these strains exogenous N2O neither directly inhibited growth nor was used significantly for growth. On the other hand, strain P2 grew abundantly on exogenous N2O when small and growth-limiting concentrations of nitrate or nitrate (2 to 10 mM) were included in the medium. The dramatic effect of these N-anions was realized in large part even when the exogenous N2O was introduced immediately after the quantitative conversion of anion-nitrogen to N2. No evidence was found for a factor in filter-sterilized spent medium that stimulated fresh inocula to grow abundantly on N2O.(ABSTRACT TRUNCATED AT 250 WORDS)


A highly conserved protein secreted by the prostate cancer cell line PC-3 is expressed in benign and malignant prostate tissue.
In this study we characterize a novel gene on human chromosome 9 and its translation product, PC3-secreted microprotein (PSMP). The gene contains three exons that encode a protein of 139 amino acid residues, including a predicted signal peptide of 36 residues. The molecule is homologous to beta-microseminoprotein (MSP), a protein of unknown function, secreted at high concentration by the prostate gland. These two proteins have only 23% sequence identity, but their common origin is revealed by a preserved pattern of Cys residues. In contrast to MSP, which shows poor conservation between species, PSMP is very conserved. High transcript levels were detected in the prostate cancer cell line PC-3. Antiserum raised against PSMP detected a protein with an apparent molecular mass of 18 kDa in culture medium conditioned by PC-3 cells, but in cell lysates the antiserum also recognized a molecular species of 16 kDa, suggesting that PSMP undergoes post-translational modification. Xenografted PC-3 cell tumors in athymic nude mice showed strong staining for both PSMP protein and mRNA. Studies on human prostate cancer specimens showed immunohistochemical staining of both tumor and benign glandular cells. Our results suggest that PSMP is an important protein with significance in prostate cancer.


Assistive technologies for managing language disorders in dementia.
At present, the number of elderly people is rapidly increasing, which represents a significant threat in terms of their care when they fall ill. One of the most common aging diseases nowadays is dementia, whose symptoms sooner or later include loss of cognitive functioning. Cognitive disorders can vary from serious mental retardation to inability to recall things, to the loss or disorder of specific cognitive functions such as communication. These disorders not only affect the quality of people's own life but also impose a substantial burden on their families, particularly on their caregivers. Therefore, the aim of this article is to highlight the role of assistive technologies (ATs) for managing language impairments in dementia in order to improve patients' quality of life. In addition, ATs focused on training patients' memory are also mentioned, since they can help patients to maintain their language skills. Furthermore, these ATs can delay the need for institutional care, as well as significantly reduce costs on patient care. The importance of future research in the area of the development of ATs for managing the language impairments in dementia is also discussed. There is a general trend toward the personalization of patient needs and requirements in the area of ATs. For the purpose of this article, a method of literature review of available sources defining language disorders and providing characteristic features of language disorders in dementia is used. In addition, a method of comparison of different research studies exploring ATs focused on delaying language disorders in dementia in order to postpone patients' need for institutional care is also exploited.


Recurrent central nervous system acute lymphoblastic leukemia associated with cerebrospinal fluid eosinophilia and basophilia: a proposed cytokine-mediated mechanism.
The authors describe a case of acute lymphoblastic leukemia with two subsequent isolated central nervous system (CNS) relapses, each accompanied by cerebrospinal fluid (CSF) eosinophilia and basophilia. Despite marked peripheral blood and bone marrow eosinophilia at initial diagnosis, the patient had no blood or bone marrow eosinophilia, basophilia, or leukemic blasts at the time of either CNS relapse. The literature is reviewed and a possible cytokine-based mechanism is proposed for the unusual finding of simultaneous CSF eosinophilia, basophilia, and leukemic blasts.


People's sensitivity to content vs. formal properties of visual stimuli: Evidence from category construction.
When people are asked to classify visual stimuli, they are often insensitive to formal properties, such as their 3D coherence or symmetry. We investigated whether this pattern of formal insensitivity would also be found using more familiar stimuli and properties: paintings that differ in their artistic style and words printed in two different typefaces. The experiments used the category formation paradigm in which subjects freely sort items into groups that seem most natural to them. They could sort each stimulus set up to three times. Only about half of the subjects in Experiment 1 ever sorted the paintings by artistic style, and only 12% did so on their first sort. Only 36% ever sorted by typeface, with many of the subjects stopping after two sorts and saying that no further categories were possible. Experiment 2 repeated the test of typeface using actual words cut out of newspapers and advertisements. Half the words were printed in boldface and half not. These items lacked any strong semantic connections, yet only 30% of subjects ever sorted the items into the bold and non-bold words. The results suggest that many people are not sensitive to the formal properties of stimuli that also have semantic content. Spontaneously noticing those differences may require a particular task with explicit instructions or experience in that domain (e.g., copyeditors or art students).


Prophylactic use of antimalarials during pregnancy.
Some of my pregnant patients wish to travel to malaria-endemic regions. Are there medications that can be used safely during pregnancy for malaria prophylaxis? Pregnant women should avoid travel to malaria-endemic areas if possible. However, if travel cannot be avoided, measures to prevent mosquito bites, along with an effective chemoprophylaxis regimen, should be implemented. Chloroquine or hydroxychloroquine are considered safe to use in all trimesters of pregnancy. Mefloquine is the agent of choice for chloroquine-resistant areas, and evidence suggests it is not associated with an increased risk to the fetus. Although the atovaquone-proguanil drug combination is not currently recommended for use during pregnancy, limited data suggest that it is not harmful to the fetus. Doxycycline and primaquine are not recommended during pregnancy.


Comparative analysis of the carrot miRNAome in response to salt stress.
Soil salinity adversely affects the yield and quality of crops, including carrot. During salt stress, plant growth and development are impaired by restricted water uptake and ion cytotoxicity, leading to nutrient imbalance and oxidative burst. However, the molecular mechanisms of the carrot plant response to salt stress remain unclear. The occurrence and expression of miRNAs that are potentially involved in the regulation of carrot tolerance to salinity stress were investigated. The results of small RNA sequencing revealed that salt-sensitive (DH1) and salt-tolerant (DLBA) carrot varieties had different miRNA expression profiles. A total of 95 miRNAs were identified, including 71 novel miRNAs, of which 30 and 23 were unique to DH1 and DLBA, respectively. The comparison of NGS and qPCR results allowed identification of two conserved and five novel miRNA involved in carrot response to salt stress, and which differentiated the salt-tolerant and salt-sensitive varieties. Degradome analysis supported by in silico-based predictions and followed by expression analysis of exemplary target genes pointed at genes related to proline, glutathione, and glutamate metabolism pathways as potential miRNA targets involved in salt tolerance, and indicated that the regulation of osmoprotection and antioxidant protection, earlier identified as being more efficient in the tolerant variety, may be controlled by miRNAs. Furthermore, potential miRNA target genes involved in chloroplast protection, signal transduction and the synthesis and modification of cell wall components were indicated in plants growing in saline soil.


Prevalence of serotype specific antibody to equine encephalosis virus in Thoroughbred yearlings in South Africa (1999-2004).
Cohorts of yearlings were sampled over a period of 6 years in a retrospective serological survey to establish the annual prevalence of serotype specific antibody to equine encephalosis virus on Thoroughbred stud farms distributed within defined geographical regions of South Africa. Seasonal seroprevalence varied between 3.6% and 34.7%, revealing both single and multiple serotype infections in an individual yearling. During the course of this study serotypes 1 and 6 were most frequently and extensively identified while the remaining serotypes 2, 3, 4, 5 and 7 were all identified as sporadic and localized infections affecting only individual horses. This study of the seasonal prevalence of equine encephalosis virus has a corollary and serves as a useful model in the seasonal incidence of the serotypes of African horse sickness and bluetongue in regions where the respective diseases are endemic.


Strategic Replication of the Hepatic Zonation In Vitro Employing a Biomimetic Approach.
The varied functions of the liver are dependent on the metabolic heterogeneity exhibited by the hepatocytes within the liver lobule spanning the porto-central axis. This complex phenomenon plays an important role in maintaining the physiological homeostasis of the liver. Standard in vitro culture models fail to mimic this spatial heterogeneity of hepatocytes, assuming a homogeneous population of cells, which leads to inaccurate translation of results. Here, we demonstrate the development of an in vitro model of hepatic zonation by mimicking the microarchitecture of the liver using a 3D printed mini bioreactor and decellularized liver matrix to provide the native microenvironmental cues. There was a differential expression of hypoxic and metabolic markers across the developed mini bioreactor, showing the establishment of gradients of oxygen, Wnt/β-catenin pathway, and other metabolic pathways. The model also showed the establishment of zone-dependent toxicity on treatment with acetaminophen. The developed model would thus be a promising avenue in the field of tissue engineering for understanding the liver physiology and pathophysiology and for drug screening to evaluate the potential of new pharmaceutical interventions.


A computer-aided detection of EEG seizures in infants: a singular-spectrum approach and performance comparison.
This paper presents a scalp electroencephalogram (EEG) seizure detection scheme based on singular spectrum analysis (SSA) and Rissanen minimum description length (MDL) model-order selection (SSA-MDL). Preprocessing of the signals allows for the drastic reduction of the number of false alarms. Statistical performance comparison with seizure detection schemes of Gotman et al. and Liu et al. is performed on both synthetic data and real EEG seizures. Monte Carlo simulations based on synthetic infant EEG seizure data reveals some detection drawbacks on a large variety of seizure waveforms. Detection using both Monte Carlo and four real infant scalp EEG signals shows the superiority of the SSA-MDL method with an average good detection rate of >93% and false detection rate <4%.


A cluster analytic examination and external validation of psychopathic offender subtypes in a multisite sample of Canadian federal offenders.
The present study is a cluster analytic examination and validation of psychopathic offender subtypes from 4 combined samples of Canadian federally incarcerated offenders, most of whom were serving sentences for violent offenses. The men were rated on the Hare Psychopathy Checklist-Revised (PCL-R; Hare, 1991, 2003) on the basis of comprehensive file information and 314 cases were extracted using a PCL-R total cut score of 25. Cluster analysis of the 4 PCL-R facets converged at a 2-cluster solution: a primary subtype characterized by prominent interpersonal and affective features of psychopathy and a secondary subtype characterized by comparatively few interpersonal features and high scores on the remaining facets. Validation analyses found that the vast majority of primary psychopathic offenders (74.1%) were White or of non-Aboriginal descent in contrast to the secondary subtype (47.6%). Secondary psychopathic offenders tended to be actuarially higher risk, have greater criminogenic needs, and to make greater amounts of treatment change on criminogenic targets; however, contrary to expectations, within-treatment changes from a violence reduction program were significantly associated with reductions in violent recidivism for primary, but not secondary, variants. There were few differences in rates of recidivism between the groups overall; secondary variants had higher rates of sexual violence which was largely accounted for by individual differences in baseline static risk. Implications for risk assessment, treatment planning, and the classification and etiology of primary and secondary psychopathy are discussed.


Single-electron reduction of the oxidized state is coupled to proton uptake via the K pathway in Paracoccus denitrificans cytochrome c oxidase.
The reductive part of the catalytic cycle of cytochrome c oxidase from Paracoccus denitrificans was examined by using time-resolved potential measurements on black lipid membranes. Proteoliposomes were adsorbed to the black lipid membranes and Ru(II)(2, 2'-bipyridyl)(3)(2+) was used as photoreductant to measure flash-induced membrane potential generation. Single-electron reduction of the oxidized wild-type cytochrome c oxidase reveals two phases of membrane potential generation (tau(1) approximately 20 micros and tau(2) approximately 175 micros) at pH 7.4. The fast phase is not sensitive to cyanide and is assigned to electron transfer from Cu(A) to heme a. The slower phase is inhibited completely by cyanide and shows a kinetic deuterium isotope effect by a factor of 2-3. Although two enzyme variants mutated in the so-called D pathway of proton transfer (D124N and E278Q) show the same time constants and relative amplitudes as the wild-type enzyme, in the K pathway variant K354M, tau(2) is increased to 900 micros. This result suggests uptake of a proton through the K pathway during the transition from the oxidized to the one-electron reduced state. After the second laser flash under anaerobic conditions, a third electrogenic phase with a time constant of approximately 1 ms appears. The amplitude of this phase grows with increasing flash number. We explain this growth by injection of a second electron into the single-electron reduced enzyme. On multiple flashes, both D pathway mutants behave differently compared with the wild type and two additional slow phases of tau(3) approximately 2 ms and tau(4) approximately 15 ms are observed. These results suggest that the D pathway is involved in proton transfer coupled to the uptake of the second electron.


Barriers to brain health behaviours: results from the Five Lives Brain Health Ireland Survey.
Modifiable risk factors for dementia remain prevalent in Ireland. A detailed examination of barriers to risk reduction behaviours in an Irish context has heretofore been lacking. Many existing studies examining barriers to brain health behaviours fail to examine how they might vary across different modifiable risk factors. This study undertook a detailed assessment of barriers to individual risk reduction behaviours. As existing research suggests that barriers may vary across sociodemographic factors, we sought to investigate the distribution of barriers across age, gender, educational status, and household income. The Five Lives Brain Health Ireland Survey is a cross-sectional survey that was distributed online amongst a non-patient population. The survey captured the following: (1) Sociodemographic factors; (2) Barriers to brain health behaviours; (3) Exposure to, and knowledge of, modifiable risk factors for dementia, namely diet, social interaction, exercise, hypertension, sleep, current low mood/depression, current smoking, alcohol consumption, cognitive stimulation, hearing impairment, diabetes, air pollution, and head injury; (4) Participants' perceptions regarding potential for dementia prevention, and risk reduction. Lack of motivation was the most prevalent barrier to consuming a healthy diet (64%, n = 213), physical activity (77.7%, n = 167), smoking cessation (68%, n = 85), and moderation of alcohol intake (56.3%, n = 67). Practical factors were the most prevalent barriers to addressing low mood (56.5%, n = 87), air pollution (30.1%, n = 58), hearing impairment (63.8%, n = 44), diabetes (11.1%, n = 5), and head injury (80%, n = 8). Emotional factors were the most prevalent barriers to engaging in mentally stimulating activity (56.9%, n = 66), social activity (54.9%, n = 302), and good sleep (70.1%, n = 129). Lack of knowledge was the most prevalent barrier to hypertension control (14.4%, n = 29). Distribution of barriers varied across age, gender, educational status, and household income. This study investigated barriers to lifestyle change to improve brain health in an Irish sample of adults aged 50 and above. Detailed subtyping of barriers, as well as examination of differences according to age, gender, education, and income were undertaken. The heterogeneity of barriers to brain health behaviours revealed in this study highlights the necessity to tailor public health interventions to their target population, taking into account the gender, age, educational status, and income of recipients.


Primary cilia disassembly down-regulates mechanosensitive hedgehog signalling: a feedback mechanism controlling ADAMTS-5 expression in chondrocytes.
Hedgehog signalling is mediated by the primary cilium and promotes cartilage degeneration in osteoarthritis. Primary cilia are influenced by pathological stimuli and cilia length and prevalence are increased in osteoarthritic cartilage. This study aims to investigate the relationship between mechanical loading, hedgehog signalling and cilia disassembly in articular chondrocytes. Primary bovine articular chondrocytes were subjected to cyclic tensile strain (CTS; 0.33 Hz, 10% or 20% strain). Hedgehog pathway activation (Ptch1, Gli1) and A Disintegrin And Metalloproteinase with Thrombospondin Motifs 5 (ADAMTS-5) expression were assessed by real-time PCR. A chondrocyte cell line generated from the Tg737(ORPK) mouse was used to investigate the role of the cilium in this response. Cilia length and prevalence were quantified by immunocytochemistry and confocal microscopy. Mechanical strain upregulates Indian hedgehog expression and activates hedgehog signalling. Ptch1, Gli1 and ADAMTS-5 expression were increased following 10% CTS, but not 20% CTS. Pathway activation requires a functioning primary cilium and is not observed in Tg737(ORPK) cells lacking cilia. Mechanical loading significantly reduced cilium length such that cilia became progressively shorter with increasing strain magnitude. Inhibition of histone deacetylase 6 (HDAC6), a tubulin deacetylase, prevented cilia disassembly and restored mechanosensitive hedgehog signalling and ADAMTS-5 expression at 20% CTS. This study demonstrates for the first time that mechanical loading activates primary cilia-mediated hedgehog signalling and ADAMTS-5 expression in adult articular chondrocytes, but that this response is lost at high strains due to HDAC6-mediated cilia disassembly. The study provides new mechanistic insight into the role of primary cilia and mechanical loading in articular cartilage.


The prevalence, antibiotic resistance and mecA characterization of coagulase negative staphylococci recovered from non-healthcare settings in London, UK.
Coagulase negative staphylococci (CoNS) are important reservoirs of antibiotic resistance genes and associated mobile genetic elements and are believed to contribute to the emergence of successful methicillin resistant Staphylococcus aureus (MRSA) clones. Although, these bacteria have been linked to various ecological niches, little is known about the dissemination and genetic diversity of antibiotic resistant CoNS in general public settings. Four hundred seventy-nine samples were collected from different non-healthcare/general public settings in various locations (n = 355) and from the hands of volunteers (n = 124) in London UK between April 2013 and Nov 2014. Six hundred forty-three staphylococcal isolates belonging to 19 staphylococcal species were identified. Five hundred seventy-two (94%) isolates were resistant to at least one antibiotic, and only 34 isolates were fully susceptible. Sixty-eight (11%) mecA positive staphylococcal isolates were determined in this study. SCCmec types were fully determined for forty-six isolates. Thirteen staphylococci (19%) carried SCCmec V, followed by 8 isolates carrying SCCmec type I (2%), 5 SCCmec type IV (7%), 4 SCCmec type II (6%), 1 SCCmec type III (2%), 1 SCCmec type VI (2%), and 1 SCCmec type VIII (2%). In addition, three isolates harboured a new SCCmec type 1A, which carried combination of class A mec complex and ccr type 1.MLST typing revealed that all S. epidermidis strains possess new MLST types and were assigned the following new sequence types: ST599, ST600, ST600, ST600, ST601, ST602, ST602, ST603, ST604, ST605, ST606, ST607 and ST608. The prevalence of antibiotic resistant staphylococci in general public settings demonstrates that antibiotics in the natural environments contribute to the selection of antibiotic resistant microorganisms. The finding of various SCCmec types in non-healthcare associated environments indicates the complexity of SCCmec. We also report on new MLST types that were assigned for all S. epidermidis isolates, which demonstrates the genetic variability of these isolates.


Fertility, infertility and generation replacement.
Throughout most of human history 'natural fertility' and life expectations of about 35 years kept population numbers reasonably balanced; but the achievement of life expectations of 75 or more years destroyed this 'natural' system. As longevity increased amongst Western peoples, explosive growth rates were only prevented by increasingly efficient checks on fertility. Today, these checks are so universal and so efficient in Australia and in many other Western countries that 'intrinsic' levels of fertility are below generation replacement level. Changes in fecundity were not a significant factor in this demographic revolution; at least 10-12% of couples remain without issue, but the prime cause of the change is the evolution of the two-child family, a process which now involves only about a sixth of a couple's fecund married life. For the rest of their years most couples are now voluntarily infertile. Correction of involuntary sterility is important to individual couples but has little significance in terms of generation replacement.


Genome-wide Runx2 occupancy in prostate cancer cells suggests a role in regulating secretion.
Runx2 is a metastatic transcription factor (TF) increasingly expressed during prostate cancer (PCa) progression. Using PCa cells conditionally expressing Runx2, we previously identified Runx2-regulated genes with known roles in epithelial-mesenchymal transition, invasiveness, angiogenesis, extracellular matrix proteolysis and osteolysis. To map Runx2-occupied regions (R2ORs) in PCa cells, we first analyzed regions predicted to bind Runx2 based on the expression data, and found that recruitment to sites upstream of the KLK2 and CSF2 genes was cyclical over time. Genome-wide ChIP-seq analysis at a time of maximum occupancy at these sites revealed 1603 high-confidence R2ORs, enriched with cognate motifs for RUNX, GATA and ETS TFs. The R2ORs were distributed with little regard to annotated transcription start sites (TSSs), mainly in introns and intergenic regions. Runx2-upregulated genes, however, displayed enrichment for R2ORs within 40 kb of their TSSs. The main annotated functions enriched in 98 Runx2-upregulated genes with nearby R2ORs were related to invasiveness and membrane trafficking/secretion. Indeed, using SDS-PAGE, mass spectrometry and western analyses, we show that Runx2 enhances secretion of several proteins, including fatty acid synthase and metastasis-associated laminins. Thus, combined analysis of Runx2's transcriptome and genomic occupancy in PCa cells lead to defining its novel role in regulating protein secretion.


A novel high-throughput scanning microscope for label-free detection of protein and small-molecule chemical microarrays.
We describe a novel scanning optical microscope based on a polarization-modulated nulling ellipsometry. The new microscope employs a combination of scanning mirror and sample translation and thus enables high-throughput label-free detection of biomolecular microarrays with more than 10 000 protein or small-molecule targets. For illustration, we show the image of a 2760-spot protein microarray on a functionalized glass slide obtained with such a microscope. The new scanning microscope is also capable of determining, in parallel, the real-time binding kinetics of multiple molecular species under aqueous conditions.


Bimetallic Au-Ni nanoparticles embedded in SiO2 nanospheres: synergetic catalysis in hydrolytic dehydrogenation of ammonia borane.
Gold-nickel nanoparticles (NPs) of 3-4 nm diameter embedded in silica nanospheres of around 15 nm have been prepared by using [Au(en)(2)Cl(3)] and [Ni(NH(3))(6)Cl(2)] as precursors in a NP-5/cyclohexane reversed-micelle system, and by in situ reduction in an aqueous solution of NaBH(4)/NH(3)BH(3). Compared with monometallic Au@SiO(2) and Ni@SiO(2), the as-synthesized Au-Ni@SiO(2) catalyst shows higher catalytic activity and better durability in the hydrolysis of ammonia borane, generating a nearly stoichiometric amount of hydrogen. During the generation of H(2), the synergy effect between gold and nickel is apparent: The nickel species stabilizes the gold NPs and the existence of gold helps to improve the catalytic activity and durability of the nickel NPs.


Suicide with remifentanil and midazolam : a case report.
Background : Remifentanil (Ultiva®) is a recently introduced esterase-metabolized potent opioid (EMO) μ-receptor agonist with a rapid onset and offset of action for use as part of general anaesthesia in association with isoflurane or propofol or with midazolam (Dormicum®) and in combination with mivacurium. Case Report : A nurse from the anaesthesiology department of a hospital was found dead at home with a syringe and empty vials of Ultiva® (2 mg) and of Dormicum ® (1 mg/mL). At autopsy several injection sites were found on her body. Usual toxicology screening operated in our laboratory revealed only the presence of benzodiazepines in blood. Regarding the case history, we decided to adapt a method specially designed for remifentanil and its inactive metabolite testing. The analytes were isolated by SPE on a Clean-Screen column. After silylation with BSTFA with 1% TMCS, the analytes were detected by GC/MS-EI operating in the SIM mode. No Remifentanil could be detected, whereas the metabolite of remifentanil GR90291 was determined in femoral blood, liver, kidney and lung. Furthermore, midazolam could be detected in femoral and cardiac blood. Hair analysis of a segment of 5 cm revealed the presence of diazepam and midazolam, whereas neither remifentanil nor its metabolite could be detected.


Circulatory responses to nasotracheal intubation: comparison of GlideScope videolaryngoscope and Macintosh direct laryngoscope.
The GlideScope videolaryngoscope (GSVL) has been shown to have no special advantage over the Macintosh direct laryngoscope (MDL) in attenuating the circulatory responses to orotracheal intubation, but no study has compared the circulatory responses to nasotracheal intubation (NTI) using the two devices. This prospective randomized clinical study was designed to determine whether there was a clinically relevant difference between the circulatory responses to NTI with the GSVL and the MDL. Seventy-six adult patients were randomly allocated equally to the GSVL group and the MDL group. After induction of anesthesia, NTI was performed. Non-invasive blood pressure (BP) and heart rate (HR) were recorded before induction (baseline values) and immediately before intubation (post-induction values), at intubation and every minute for a further five minutes. During the observation, times required to reach the maximum values of systolic BP (SBP) and HR, times required for recovery of SBP and HR to postinduction values and incidence of SBP and HR percent changes > 30% of baseline values were also noted. The product of HR and systolic BP, i.e. rate pressure product (RPP), and the areas under SBP and HR vs. time curves (AUC(SBP) and AUC(HR)) were calculated. The NTI with the GSVL resulted in significant increases in BP, HR and RPP compared to postinduction values, but these circulatory changes did not exceed baseline values. BPs at all measuring points, AUC(SBP), maximum values of BP and incidence of SBP percent increase > 30% of baseline value during the observation did not differ significantly between groups. However, HR and RPP at intubation and their maximum values, AUC(HR) and incidence of HR percent increase > 30% of baseline value were significantly higher in the MDL group than in the GSVL group. Times required for recovery of SBP and HR to postinduction values were significantly longer in the MDL group than in the GSVL group. The pressor response to NTI with the GSVL and the MDL was similar, but the tachycardiac response to NTI was lesser and of a shorter duration when using a GSVL than when using an MDL.


The anticancer agent di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone (Dp44mT) overcomes prosurvival autophagy by two mechanisms: persistent induction of autophagosome synthesis and impairment of lysosomal integrity.
Autophagy functions as a survival mechanism during cellular stress and contributes to resistance against anticancer agents. The selective antitumor and antimetastatic chelator di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone (Dp44mT) causes lysosomal membrane permeabilization and cell death. Considering the integral role of lysosomes in autophagy and cell death, it was important to assess the effect of Dp44mT on autophagy to further understand its mechanism of action. Notably, Dp44mT affected autophagy by two mechanisms. First, concurrent with its antiproliferative activity, Dp44mT increased the expression of the classical autophagic marker LC3-II as a result of induced autophagosome synthesis. Second, this effect was supplemented by a reduction in autophagosome degradation as shown by the accumulation of the autophagic substrate and receptor p62. Conversely, the classical iron chelator desferrioxamine induced autophagosome accumulation only by inhibiting autophagosome degradation. The formation of redox-active iron or copper Dp44mT complexes was critical for its dual effect on autophagy. The cytoprotective antioxidant N-acetylcysteine inhibited Dp44mT-induced autophagosome synthesis and p62 accumulation. Importantly, Dp44mT inhibited autophagosome degradation via lysosomal disruption. This effect prevented the fusion of lysosomes with autophagosomes to form autolysosomes, which is crucial for the completion of the autophagic process. The antiproliferative activity of Dp44mT was suppressed by Beclin1 and ATG5 silencing, indicating the role of persistent autophagosome synthesis in Dp44mT-induced cell death. These studies demonstrate that Dp44mT can overcome the prosurvival activity of autophagy in cancer cells by utilizing this process to potentiate cell death.


Paclitaxel as the initial treatment of multiple myeloma: an Eastern Cooperative Oncology Group Study (E1A93).
The authors assess the activity and toxicity of paclitaxel in previously untreated patients with multiple myeloma. Eighteen patients with previously untreated multiple myeloma were enrolled. Paclitaxel was given in a dose of 250 mg/m2 by a continuous intravenous infusion for 24 hours every 21 days for four cycles. All patients received granulocyte colony stimulating factor in a dose of 5 microg/kg each day until the absolute neutrophil count was 10,000/mm3. All patients were evaluated after four cycles. Four (29%) objective responses were observed in the 14 eligible patients. No complete responses occurred. Three lethal toxicities were observed, two were the result of neutropenic sepsis. Sixty-one percent of patients experienced some type of severe nonhematologic toxicity. Patients who received four cycles of paclitaxel were given further treatment at the discretion of the investigator. The median survival of all eligible patients was 2.8 years, which is comparable with the median survival with melphalan and prednisone of 2.3 years or vincristine, carmustine, melphalan, cylophosphamide, and prednisone of 2.4 years. Paclitaxel in the dosage used in this study has prohibitive toxicity. The four (29%) responses in 14 evaluable untreated patients indicates that paclitaxel is active in the treatment of multiple myeloma. No complete remissions were recorded. Further studies using paclitaxel in a smaller dose, in combination with other agents, or using one of the paclitaxel analogs may be useful in the treatment of multiple myeloma.


Development of a PCR assay for rapid diagnosis of Mycobacterium ulcerans infection.
The diagnosis of Mycobacterium ulcerans infection is hampered by the slow growth of the bacterium in culture, resulting in a delay of several months before a specific diagnosis can be obtained. In addition, M. ulcerans cannot be isolated from water even when there is convincing epidemiological evidence implicating this as the source of infection. The aim of the present study was to develop a PCR assay to circumvent the problems of delayed diagnosis and insensitivity of standard bacterial culture for M. ulcerans. For the PCR, we isolated an M. ulcerans-specific DNA fragment, 1,109 bp long, which is repeated at least 50 times throughout the genome. Use of this sequence as a target for PCR allowed us to detect as few as 2 molecules of genomic DNA in vitro. The PCR was used to detect M. ulcerans DNA in fresh tissue and paraffin-embedded sections from all seven patients with culture-confirmed cases of infection.


Serum markers of the extracellular matrix remodeling reflect antifibrotic therapy in bile-duct ligated rats.
Progression of liver fibrosis is characterized by synthesis and degradation of extracellular matrix (ECM). Matrix-metalloproteinases (MMP) cleave collagen fibers at a specific site and thereby generate soluble fragments of ECM (neo-epitopes). The levels of these neo-epitopes might reflect the stage of liver fibrosis and may allow monitoring of anti-fibrotic therapies. Here we analyzed these neo-epitopes as read-out for a liver directed therapy with statins. Bile duct ligation (BDL) was performed on wild type rats, which received atorvastatin (15 mg/kg(*)d) for 1 week starting at 1, 2, 3, 4 and 5 weeks after BDL (T1-T5), while controls remained untreated. Hepatic fibrosis was analyzed by immunohistochemistry and hepatic hydroxyproline content. TGFβ levels were measured by RT-PCR. Proteolytic activity of MMP-2 was examined by zymography. Levels of degradation MMP driven type I, III, IV and VI collagen degradation (C1M, C3M, C4M, and C6M) and type III and IV collagen formation (PRO-C3 and P4NP7S) markers were assessed by specific ELISAs in serum probes. Serum markers of ECM neo-epitopes reflected significantly the deposition of ECM in the liver and were able to distinguish between early (T1-T3) and severe fibrosis (T4-T5). Statin treatment resulted in reduction of neo-epitope markers, especially when therapy was started in the stage of severe fibrosis (T4-T5). Furthermore, these markers correlated with hepatic expression of profibrotic cytokines TGFβ1 and TGFβ2. Formation markers of type III and IV collagen (PRO-C3 and P4NP7S) and degradation markers C4M and C6M correlated significantly with hepatic MMP-2 activity in rats with severe fibrosis. Determination of ECM remodeling turnover markers in serum allowed a distinction between mild and severe fibrosis. With respect to statin therapy, the markers may serve as read-out for efficacy of anti-fibrotic treatment.


Towards Trustworthy Energy Disaggregation: A Review of Challenges, Methods, and Perspectives for Non-Intrusive Load Monitoring.
Non-intrusive load monitoring (NILM) is the task of disaggregating the total power consumption into its individual sub-components. Over the years, signal processing and machine learning algorithms have been combined to achieve this. Many publications and extensive research works are performed on energy disaggregation or NILM for the state-of-the-art methods to reach the desired performance. The initial interest of the scientific community to formulate and describe mathematically the NILM problem using machine learning tools has now shifted into a more practical NILM. Currently, we are in the mature NILM period where there is an attempt for NILM to be applied in real-life application scenarios. Thus, the complexity of the algorithms, transferability, reliability, practicality, and, in general, trustworthiness are the main issues of interest. This review narrows the gap between the early immature NILM era and the mature one. In particular, the paper provides a comprehensive literature review of the NILM methods for residential appliances only. The paper analyzes, summarizes, and presents the outcomes of a large number of recently published scholarly articles. Furthermore, the paper discusses the highlights of these methods and introduces the research dilemmas that should be taken into consideration by researchers to apply NILM methods. Finally, we show the need for transferring the traditional disaggregation models into a practical and trustworthy framework.


Effect of fiber source and crude protein level on nursery pig performance and fecal microbial communities.
Reduction in dietary crude protein and addition of fiber could mitigate the incidence and severity of post-weaning diarrhea, a common gastrointestinal condition in newly weaned pigs. Therefore, 360 weanling pigs, initially 5.0 ± 0.10 kg, were used to evaluate the effects of crude protein (CP) level and fiber source on growth performance and fecal microbial communities. At weaning, pigs were randomly assigned to pens and allotted to 1 of 8 dietary treatments in a 2 × 4 factorial with main effects of CP (21 or 18%) and fiber source (none, coarse wheat bran, oat hulls, or cellulose). There were 5 pigs per pen and 9 pens per treatment. Experimental diets were formulated in two dietary phases from d 0 to 10 and 10 to 24, with a common post-treatment diet fed from 24 to 45. The 21% CP diets contained 1.40% standardized ileal digestible (SID) Lys in phase 1 and 1.35% SID Lys in phase 2. By using a maximum SID Lys:digestible CP ratio of 6.35%, the 18% CP diets contained 1.25% SID Lys in both phases. Diets containing a fiber source were formulated to the level of insoluble fiber provided by 4% coarse wheat bran, resulting in the addition of 1.85% oat hulls and 1.55% cellulose. No fiber source × CP level interactions (P > 0.05) were observed. Decreasing CP (and subsequently SID lysine) decreased (P = 0.05) ADG and G:F during the experimental period. From d 0 to 45, ADG decreased (P = 0.05) for pigs fed 18% CP diets compared to pigs fed 21% CP. No effect of fiber source was observed for growth performance. Fecal DM on d 17 increased (P < 0.001) for pigs fed 18% CP diets compared to pigs fed 21% CP diets. Pigs fed diets with added cellulose had increased (P < 0.05) fecal dry matter during the experimental period compared to pigs fed no fiber source or wheat bran. Bacterial community structure was investigated by sequencing the V4 region of the 16S rRNA gene. Analysis indicated a significant difference between CP content at d 24 (P = 0.023) using a Weighted UniFrac distance matrix. Further investigation identified five differential Amplicon Sequence Variants associated with CP content at d 24. In conclusion, reducing crude protein (and subsequently SID Lys) decreased growth performance but increased fecal dry matter content. The source of dietary fiber in nursery diets had no impact on growth performance; but pigs fed added cellulose had increased fecal DM compared with other treatments. Microbial analysis identified differential taxa associated with CP content.


Safety and Quality of Canned Sardines after Opening: A Shelf-Stability Study.
This study aimed to define the shelf life of canned sardines after opening to increase consumer awareness of their quality and safety and reduce food waste. For this purpose, canned sardines (Sardina pilchardus) packed with different sauces were opened and stored at 4 °C for 7 days. Microbiological, sensorial, physical and chemical stability was monitored daily by standard methodologies. Results show that the overall quality and safety are highly dependent on the sauce type. To preserve their full quality, sardines in brine and in vegetable oil should be consumed up to 1 day after opening, while sardines in tomato sauce were stable for up to 3 days, although none were considered nonedible up to the 7th day. Many parameters demonstrated statistical differences and correlations with storage, although they were not as decisive as sensory evaluation. This integrated approach should be adopted by the food industry and regulating authorities to provide information to consumers regarding the quality and safety of handled goods.


Fish as indicators of disturbance in streams used for snorkeling activities in a tourist region.
A set of metrics that reflect various aspects of population and fish community structure in streams used for snorkeling was evaluated in the tourist region of Bodoquena Plateau, Brazil, with the purpose of biomonitoring the impacts of such activities. Observations were made while snorkeling in two sites (active = with tourism; inactive = without tourism) and along the gradient of daily tourist activity (before, during and after the passage of tourists) in two streams. Five metrics discriminated active from inactive sites: (i) the abundance of Crenicichla lepidota and (ii) the incidence of reproductive activity in Crenicichla lepidota which were greater in inactive sites, regardless the gradient of daily tourist activity; (iii) the feeding pattern of Prochilodus lineatus, which differed among sites and along the gradient of daily tourist activity; (iv) the abundance of Moenkhausia bonita, which was higher in the active sites and significantly increased along the gradient of daily tourist activity in one stream but decrease along the gradient in other stream; (v) the abundance of Hyphessobrycon eques, which was greater in inactive sites, regardless the gradient of daily tourist activity. With the exception of metric "iv", the metrics were mediated by the reduction in habitat structural complexity due to snorkeling disturbance. The definition of these metrics is relevant because the degradation of ecosystem structural elements is one of the main impacts of recreational activities on aquatic environments. The easy recognition of target species and high water transparency throughout the year ensures the feasibility of these metrics in monitoring programs and may be applied by technicians after quick guides and training.


Characterization of cigarette tobacco by direct electrospray ionization-ion trap mass spectrometry (ESI-ITMS) analysis of the aqueous extract--a novel and simple approach.
In support of the efforts to combat smuggling, as well as illegal sale and distribution of cigarettes, an analytical approach for the characterization of tobacco has been proposed and evaluated. It involves aqueous extraction of the filler tobaccos followed by direct analysis of the extracts by electrospray ionization-ion trap mass spectrometry (ESI-ITMS) in the negative mode. Typically, the deprotonated ions, [M - H](-), of organic acids (malic, citric, caffeic, quinic acid) and polyphenols (chlorogenic acid, rutin, scopoletin) were detected. MS/MS spectra of the ion at m/z 191, which is the [M - H](-) of quinic acid, citric acid, and scopoletin, and a fragment ion of chlorogenic acid were acquired. Significant differences in the MS and MS/MS spectra were observed between counterfeit samples and the corresponding authentic brand name cigarettes. Analysis of 25 commercial cigarettes showed that straight Virginia blends were readily distinguished from the blended products containing different tobacco types (Virginia, burley, and Oriental). The former exhibited consistently higher relative abundances of m/z 353 (chlorogenic acid) to m/z 133 (malic acid) in the MS spectra (0.9-1.2 vs 0.4-0.6) and higher intensity ratios of m/z 176 (scopoletin) to m/z 173 (0.4-0.8 vs 0.1-0.3) and of m/z 127 (quinic acid) to m/z 173 (0.7-1.0 vs 0.3-0.5) in the MS/MS spectra. Evidence is presented to demonstrate that the spectral differences were related not only to the tobacco type (Virginia, burley and Oriental) but also to the tobacco part (stem, lamina) used in the manufacture of the cigarettes.


A string pattern regression algorithm and its application to pattern discovery in long introns.
We present a new approach to pattern discovery called string pattern regression, where we are given a data set that consists of a string attribute and an objective numerical attribute. The problem is to find the best string pattern that divides the data set in such a way that the distribution of the numerical attribute values of the set for which the pattern matches the string attribute, is most distinct, with respect to some appropriate measure, from the distribution of the numerical attribute values of the set for which the pattern does not match the string attribute. By solving this problem, we are able to discover, at the same time, a subset of the data whose objective numerical attributes are significantly different from rest of the data, as well as the splitting rule in the form of a string pattern that is conserved in the subset. Although the problem can be solved in linear time for the substring pattern class, the problem is NP-hard in the general case (i.e. more complex patterns), and we present an exact but efficient branch-and-bound algorithm which is applicable to various pattern classes. We apply our algorithm to intron sequences of human, mouse, fly, and zebrafish, and show the practicality of our approach and algorithm. We also discuss possible extensions of our algorithm, as well as promising applications, such as microarray gene expression data.


Pretreatment of serum containing hemoglobin vesicles (oxygen carriers) to prevent their interference in laboratory tests.
Hemoglobin vesicles (HbV, diameter: 251 +/- 81 nm) are artificial oxygen (O2) carriers encapsulating concentrated hemoglobin (Hb) solution with phospholipid bilayer membrane, and their O2 transporting ability in vivo has been extensively studied. It is important to clarify the interference of the HbV suspension in clinical laboratory tests performed on serum and to establish a pretreatment method to avoid such an interference. The HbV suspension, acellular Hb solution ([Hb] = 10 g/dl) or saline, was mixed with a pooled human serum at various ratios up to 50 vol% ([Hb] = 5 g/dl), and the magnitude of the interference effect of HbV and Hb on 30 analytes was studied. The mixture of the HbV suspension and serum was ultracentrifuged (50,000 g, 20 min) to remove the HbV particles as precipitate, and the supernatant was analyzed and compared with the saline control group. The HbV particles were also removed by centrifugation (2,700 g, 30 min) in the presence of dextran (Mw 200 kDa). The HbV suspension showed considerable interference effects in most analytes. The majority of these effects was more serious than those of the acellular Hb solution. These findings are thought to be due to the light absorption of Hb in HbV and/or the light scattering generated in the suspension that interferes with the colorimetric and turbidimetric measurements. The components of HbV may also interfere with the chemical reactions of the studied assays. However, removal of the HbV from the supernatant diminished the interference in most of the assays: this is an advantage of HbV in comparison with acellular chemically modified Hb solutions.


Chemokine (C-X-C motif) ligand 1 is a myokine induced by palmitate and is required for myogenesis in mouse satellite cells.
The functional significance of the myokines, cytokines and peptides produced and released by muscle cells has not been fully elucidated. The purpose of this study was to identify a myokine with increased secretion levels in muscle cells due to saturated fatty acids and to examine the role of the identified myokine in the regulation of myogenesis. Human primary myotubes and mouse C2C12 myotubes were used to identify the myokine; its secretion was stimulated by palmitate loading. The role of the identified myokine in the regulation of the activation, proliferation, differentiation and self-renewal was examined in mouse satellite cells (skeletal muscle stem cells). Palmitate loading promoted the secretion of chemokine (C-X-C motif) ligand 1 (CXCL1) in human primary myotubes, and it also increased CXCL1 gene expression level in C2C12 myotubes in a dose- and time-dependent manner. Palmitate loading increased the production of reactive oxygen species along with the activation of nuclear factor-kappa B (NF-κB) signalling. Pharmacological inhibition of NF-κB signalling attenuated the increase in CXCL1 gene expression induced by palmitate and hydrogen peroxide. Palmitate loading significantly increased CXC receptor 2 gene expression in undifferentiated cells. CXCL1 knockdown attenuated proliferation and myotube formation by satellite cells, with reduced self-renewal. CXCL1 knockdown also significantly decreased the Notch intracellular domain protein level. These results suggest that secretion of the myokine CXCL1 is stimulated by saturated fatty acids and that CXCL1 promotes myogenesis from satellite cells to maintain skeletal muscle homeostasis.


Regulation of human trophoblast GLUT1 glucose transporter by insulin-like growth factor I (IGF-I).
Glucose transport to the fetus across the placenta takes place via glucose transporters in the opposing faces of the barrier layer, the microvillous and basal membranes of the syncytiotrophoblast. While basal membrane content of the GLUT1 glucose transporter appears to be the rate-limiting step in transplacental transport, the factors regulating transporter expression and activity are largely unknown. In view of the many studies showing an association between IGF-I and fetal growth, we investigated the effects of IGF-I on placental glucose transport and GLUT1 transporter expression. Treatment of BeWo choriocarcinoma cells with IGF-I increased cellular GLUT1 protein. There was increased basolateral (but not microvillous) uptake of glucose and increased transepithelial transport of glucose across the BeWo monolayer. Primary syncytial cells treated with IGF-I also demonstrated an increase in GLUT1 protein. Term placental explants treated with IGF-I showed an increase in syncytial basal membrane GLUT1 but microvillous membrane GLUT1 was not affected. The placental dual perfusion model was used to assess the effects of fetally perfused IGF-I on transplacental glucose transport and syncytial GLUT1 content. In control perfusions there was a decrease in transplacental glucose transport over the course of the perfusion, whereas in tissues perfused with IGF-I through the fetal circulation there was no change. Syncytial basal membranes from IGF-I perfused tissues showed an increase in GLUT1 content. These results demonstrate that IGF-I, whether acting via microvillous or basal membrane receptors, increases the basal membrane content of GLUT1 and up-regulates basal membrane transport of glucose, leading to increased transepithelial glucose transport. These observations provide a partial explanation for the mechanism by which IGF-I controls nutrient supply in the regulation of fetal growth.


Oesophagus bezoar diagnosed and removed endoscopically.
The authors describe the rare case of bezoar in the oesophagus. Their patient was sent to their Clinics with a diagnosed oesophageal tumor. The exact diagnosis was established by endoscopical examination. The bezoar was removed by endoscope, therefore, an operation was not necessary.


Activation of diboron reagents with Brønsted bases and alcohols: an experimental and theoretical perspective of the organocatalytic boron conjugate addition reaction.
Bases play an important role in organocatalytic boron conjugate addition reactions. The sole use of MeOH and a base can efficiently transform acyclic and cyclic activated olefins into the corresponding β-borated products in the presence of diboron reagents. Inorganic and organic bases deprotonate MeOH in the presence of diboron reagents. It is concluded, on the basis of theoretical calculations, NMR spectroscopic data, and ESI-MS experiments, that the methoxide anion forms a Lewis acid-base adduct with the diboron reagent. The sp(2) B atom of the methoxide-diboron adduct gains a strongly nucleophilic character, and attacks the electron-deficient olefin. The methanol protonates the intermediate, generating the product and another methoxide anion. This appears to be the simplest method to activate diboron reagents and make them suitable for incorporation into target organic molecules.


Reversible motor and sensory peripheral neuropathy in a patient following acute carbon monoxide intoxication.
Central nervous system complications following carbon monoxide (CO) poisoning are well reported in the literature but peripheral neuropathy is under-recognized. We report the clinical and electrophysiological studies of the transient peripheral neuropathy developed in a patient following acute CO intoxication. A 27-year-old woman was found unconscious with severe hypoxia and 34.5% serum level of carboxyhemoglobin. She progressed favourably after hyperbaric oxygen therapy. Neurological examination revealed bilateral pyramidal signs. The patient referred weakness and sensory abnormalities in her right foot. An electroencephalogram did not show focal abnormalities and brain magnetic resonance was normal. Needle electromyography of weak right tibialis anterior muscle showed a reduced recruitment pattern but no spontaneous activity. Electroneurographic evaluation revealed findings compatible with a motor and sensory peripheral neuropathy in nerves of both lower limbs. In few months complete clinical recovery was reached, and the electroneurography showed normality a year later Reversible peripheral neuropathy should be considered as a possible neurological complication following acute CO poisoning. The electrophysiological studies were essential for its diagnosis and follow up.


Occupational skin disease in hairdressers.
Irritant or allergic contact dermatitis of the hands is the main occupational hazard for hairdressers. The shampoos, dyes, and waving solutions that must be applied by hairdressers are the agents involved. There is a significant association between the development of occupationally induced hand dermatitis and a history of atopy, particularly atopic dermatitis.


Phenotypic, Phytochemical, and Transcriptomic Analysis of Black Sorghum (Sorghum bicolor L.) Pericarp in Response to Light Quality.
Black sorghum [Sorghum bicolor (L.) Moench] is characterized by the black appearance of the pericarp and production of 3-deoxyanthocyanidins (3-DOA), which are valued for their cytotoxicity to cancer cells and as natural food colorants and antioxidant additives. The black pericarp phenotype is not fully penetrant in all environments, which implicates the light spectrum and/or photoperiod as the critical factor for trait expression. In this study, black- or red-pericarp genotypes were grown under regimes of visible light, visible light supplemented with UVA or supplemented with UVA plus UVB (or dark control). Pericarp 3-DOAs and pericarp pigmentation were maximized in the black genotype exposed to a light regime supplemented with UVB. Changes in gene expression during black pericarp development revealed that ultraviolet light activates genes related to plant defense, reactive oxygen species, and secondary metabolism, suggesting that 3-DOA accumulation is associated with activation of flavonoid biosynthesis and several overlapping defense and stress signaling pathways.


Pannexins Are Potential New Players in the Regulation of Cerebral Homeostasis during Sleep-Wake Cycle.
During brain homeostasis, both neurons and astroglia release ATP that is rapidly converted to adenosine in the extracellular space. Pannexin-1 (Panx1) hemichannels represent a major conduit of non-vesicular ATP release from brain cells. Previous studies have shown that Panx1-/- mice possess severe disruption of the sleep-wake cycle. Here, we review experimental data supporting the involvement of pannexins (Panx) in the coordination of fundamental sleep-associated brain processes, such as neuronal activity and regulation of cerebrovascular tone. Panx1 hemichannels are likely implicated in the regulation of the sleep-wake cycle via an indirect effect of released ATP on adenosine receptors and through interaction with other somnogens, such as IL-1β, TNFα and prostaglandin D2. In addition to the recently established role of Panx1 in the regulation of endothelium-dependent arterial dilation, similar signaling pathways are the major cellular component of neurovascular coupling. The new discovered role of Panx in sleep regulation may have broad implications in coordinating neuronal activity and homeostatic housekeeping processes during the sleep-wake cycle.


Reduction of salivary tissue factor (thromboplastin) activity by warfarin therapy.
The coagulant of normal human saliva has been identified as tissue factor (thromboplastin, TF) by virtue of its ability to cause rapid coagulation in plasmas deficient in first-stage coagulation factors and to activate factor x in the presence of factor VII and by virtue of the fact that its activity is expressed only in the presence of factor VII and is inhibited by an antibody to TF. The TF is related to cells and cell fragments in saliva. Salivary TF activity has been found to be significantly reduced in patients taking warfarin. The decline in TF activity during induction of warfarin anticoagulation occurs during the warfarin-induced decline in vitamin-K-dependent clotting factor activity, as judged by the prothrombin time. The decrease in TF activity is not related to a reduction in salivary cell count or total protein content or to a direct effect of warfarin on the assay. It is hypothesized that the mechanism by which warfarin inhibits TF activity may be related to the mechanism by which it inhibits expression of the activity of the vitamin-K-dependent clotting factors. Inhibition of the TF activity may be involved in the antithrombotic effect of warfarin.


Role of Backbone Dipole Interactions in the Formation of Secondary and Supersecondary Structures of Proteins.
We present a generic solvated coarse-grained protein model that can be used to characterize the driving forces behind protein folding. Each amino acid is coarse-grained with two beads, a backbone, and a side chain. Although the backbone beads are modeled as polar entities, side chains are hydrophobic, polar, or charged, thus allowing the exploration of how sequence patterning determines a protein fold. The change in orientation of the atoms of the coarse-grained unit is captured by the addition of two oppositely charged dummy particles inside the backbone coarse-grained bead. These two dummy charges represent a dipole that can fluctuate, thus introducing structural polarization into the coarse-grained model. Realistic α/β content is achieved de novo without any biases in the force field toward a particular secondary structure. The dipoles created by the dummy particles interact with each other and drive the protein models to fold into unique structures depending on the amino acid patterning and presence of capping residues. We have also characterized the role of dipole-dipole and dipole-charge interactions in shaping the secondary and supersecondary structure of proteins. Formation of helix bundles and β-strands are also discussed.


The effect of the age of mice on the incidence of skin cancer.
The plausibilities of two hypotheses explaining the increased cancer incidence rate in old age caused by a constant dose of carcinogen were compared using a mouse skin painting experiment in which two groups of mice started treatment at different ages. It was shown that the hypothesis of the increased rate being caused simply by increased vulnerability of old animals was not as plausible as the alternative hypothesis of the carcinogen acting to some extent cumulatively.


Optimization of wheat straw co-composting for carrier material development.
In modern agriculture large amounts of harvesting residues are produced each year due to the increase of agricultural activities in order to maintain food production for the growing population. The development of innovative fertilizers, able to satisfy nutrient needs without adverse effects on the environment. In order to allow for effective production of a carrier material for smart fertilizers, the objective of this study is to propose a statistical method to optimize the water holding capacity (WHC) and organic matter stability properties of co-composted wheat straw (WS) by using a multi response method. We varied WS size (<1, 1-2, >2 cm), charge of Trichoderma harzianum (0, 7 and 14 discs), and nitrogen addition (0, 0.95 and 1.95 g kg-1). Optimized carrier material was characterized by a higher porosity (WHC 91.7%) than raw WS, associated to structural changes and slightly increased stability as indicated by C:N ratio of the 59.5, slightly alkaline (pH ∼ 8.0), with high OM structural complexity (E4:E6 ∼ 7,9) and enhanced sorption properties (total acidity ∼ 11.6). We conclude that the optimal treatment included co-composting of WS with fine particle size (<1 cm), with a charge of T. harzianum (14 discs), and 0.98 g kg-1 of NH4NO3 to obtain a suitable WS carrier material with high possibility to improve nutrient and water holding capacity in soil.