Virtual Reality combined with Robotic facilitated movements for pain management and sensory stimulation of the upper limb following a Brachial Plexus injury: A case study.
Brachial Plexus injuries are complex in nature caused in large by high impact traffic accidents which can lead to additional complications such as Complex Regional Pain Syndrome and even lead to amputation or the need for further surgical intervention. Treatment options to help repair the brachial plexus initially involve surgical intervention and post-surgery rehabilitation with medication to help with ongoing pain. Pain treatments used for these types of injuries are limited and differ in effectiveness. Paradigms utilising multimodal systems such as the one described in this paper based on virtual reality and robotics could yield results that are non-invasive and provide better rehabilitation outcomes for the sufferers. In this paper we present a single case study exploring whether Virtual Reality plus Haptic feedback have any practical potential for reducing upper limb pain and improving function in patients with brachial plexus injuries. The case study is presented with long standing complex combination of phantom limb and neuropathic pain. A decrease in perceived levels of pain was reported which amounts to a 50% reduction in pain from baseline and an improved range of motion. An examination of the sensory phantom map on the stump seems to indicate an early establishment of the thumb representation on the stump close to the area being stimulated with potential implications for prosthesis use.


Evaluation of N-acetylcysteine for the prevention of contrast-induced nephropathy.
Contrast-induced nephropathy (CIN) remains a leading cause of acute renal failure in hospitalized patients. N-Acetylcysteine has been studied previously for the prevention of CIN, resulting in mixed findings. The objective of this study was to determine the impact of N-acetylcysteine on the development of CIN in order to guide its use at community, teaching hospitals. Patients admitted between January 1 and December 31, 2011, receiving intravenous radiocontrast dye were included if they were compliant with two or more of the following conditions: baseline serum creatinine >1.2 mg/dL or estimated creatinine clearance <50 mL/min, age ≥75 years, diabetes mellitus, heart failure, or hypertension. The primary outcome was the difference in the proportion of patients in each group (N-acetylcysteine or no N-acetylcysteine) who developed CIN, which was defined as a ≥0.5 mg/dL increase in serum creatinine or a ≥25% increase in serum creatinine within 12-96 hours post-exposure to contrast. A total of 302 patients were included, 151 who received N-acetylcysteine and 151 who did not receive N-acetylcysteine. Patients who received N-acetylcysteine had significantly worse renal function at baseline than those who did not receive N-acetylcysteine (mean pre-contrast serum creatinine, 1.41 vs. 0.95 mg/dL, p<0.0001). A lower proportion of patients developing CIN was observed between those who received N-acetylcysteine and those who did not receive N-acetylcysteine (10.2% vs. 21.8%, p=0.0428). The use of N-acetylcysteine was likely associated with a reduced incidence of CIN in patients at risk for CIN development. Based on these results, hospitals may benefit from the development of a protocol to guide the appropriate use of N-acetylcysteine.


The t-unique coding domain is important to the transformation maintenance function of the simian virus 40 small t antigen.
The small t antigen (t) of simian virus 40, a 174-amino-acid-containing protein, when present together with the other early viral protein, large T antigen (T), plays an important role in the maintenance of simian virus 40-induced neoplastic phenotype in certain cells. Indeed, each protein functions in a complementary manner in this process. The t coding unit is composed of two segments, a 5' region of 246 nucleotides which is identical to that of the corresponding 5' region of the T coding unit and a 3' segment of 276 nucleotides which is unique. Two mutant, t-encoding genomes, one bearing a missense and the other a nonsense mutation at the same point in the t-unique coding region were constructed in vitro and found to be defective in their ability to dissolve the actin cytoskeleton of rat fibroblasts and to complement T in the growth of mouse fibroblasts in soft agar. Therefore, the unique segment of the t gene encodes a portion of the t molecule which is essential to its transformation maintenance function.


Fruit and vegetable intake and breast cancer risk defined by estrogen and progesterone receptor status: the Japan Public Health Center-based Prospective Study.
Epidemiological evidence for the impact of fruit and vegetable intake on breast cancer risk among the Japanese populations is scarce. The purpose of this study was to evaluate the association between fruit and vegetable intake and breast cancer risk among 47,289 Japanese women. The study was conducted under a population-based prospective cohort design. Dietary assessment was performed using a validated food frequency questionnaire. A Cox proportional hazards regression model was used to calculate relative risks (RRs) and their corresponding 95 % confidence intervals (CIs). During an average of 10.2 years of follow-up, 452 cases of breast cancer were newly diagnosed. No association with breast cancer risk was seen for intake of total fruits and vegetables, cruciferous vegetables, green-leaf vegetables, yellow vegetables, or tomato products in overall or postmenopausal women. Cruciferous vegetable intake was associated with a statistically significant decrease in risk of premenopausal breast cancer [multivariable-RRQ4 vs. Q1 = 0.64 (95 % CI = 0.38-1.10; p trend = .046)] and showed a marginally inverse association with ER+ PR+ tumors [RRper 100 g increment = 0.64 (95 % CI = 0.41-1.00)]. In contrast, positive associations were seen between intake of total fruits and citrus fruits and breast cancer risk in overall and premenopausal women. However, these associations for fruit were all attenuated with additional adjustment for vitamin C intake. Our results suggest an overall null association between total fruit and vegetable intake and breast cancer risk. Intake of cruciferous vegetable showed a statistically significant association with a decreased risk of breast cancer among premenopausal women.


Cost-effectiveness of minimally invasive sacroiliac joint fusion.
Sacroiliac joint (SIJ) disorders are common in patients with chronic lower back pain. Minimally invasive surgical options have been shown to be effective for the treatment of chronic SIJ dysfunction. To determine the cost-effectiveness of minimally invasive SIJ fusion. Data from two prospective, multicenter, clinical trials were used to inform a Markov process cost-utility model to evaluate cumulative 5-year health quality and costs after minimally invasive SIJ fusion using triangular titanium implants or non-surgical treatment. The analysis was performed from a third-party perspective. The model specifically incorporated variation in resource utilization observed in the randomized trial. Multiple one-way and probabilistic sensitivity analyses were performed. SIJ fusion was associated with a gain of approximately 0.74 quality-adjusted life years (QALYs) at a cost of US$13,313 per QALY gained. In multiple one-way sensitivity analyses all scenarios resulted in an incremental cost-effectiveness ratio (ICER) <$26,000/QALY. Probabilistic analyses showed a high degree of certainty that the maximum ICER for SIJ fusion was less than commonly selected thresholds for acceptability (mean ICER =$13,687, 95% confidence interval $5,162-$28,085). SIJ fusion provided potential cost savings per QALY gained compared to non-surgical treatment after a treatment horizon of greater than 13 years. Compared to traditional non-surgical treatments, SIJ fusion is a cost-effective, and, in the long term, cost-saving strategy for the treatment of SIJ dysfunction due to degenerative sacroiliitis or SIJ disruption.


Are Young Children With Cochlear Implants Sensitive to the Statistics of Words in the Ambient Spoken Language?
The purpose of this study was to determine whether children with cochlear implants (CIs) are sensitive to statistical characteristics of words in the ambient spoken language, whether that sensitivity changes in expected ways as their spoken lexicon grows, and whether that sensitivity varies with unilateral or bilateral implantation. We analyzed archival data collected from the parents of 36 children who received cochlear implantation (20 unilateral, 16 bilateral) before 24 months of age. The parents reported their children's word productions 12 months after implantation using the MacArthur Communicative Development Inventories: Words and Sentences (Fenson et al., 1993). We computed the number of words, out of 292 possible monosyllabic nouns, verbs, and adjectives, that each child was reported to say and calculated the average phonotactic probability, neighborhood density, and word frequency of the reported words. Spoken vocabulary size positively correlated with average phonotactic probability and negatively correlated with average neighborhood density, but only in children with bilateral CIs. At 12 months postimplantation, children with bilateral CIs demonstrate sensitivity to statistical characteristics of words in the ambient spoken language akin to that reported for children with normal hearing during the early stages of lexical development. Children with unilateral CIs do not.


Tigecycline resistance among carbapenem-resistant Klebsiella Pneumoniae: Clinical characteristics and expression levels of efflux pump genes.
Tigecycline is a treatment option for infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP). Emerging tigecycline resistance in CRKP represents a growing threat. Knowledge of the clinical, microbiological, and molecular characteristics of tigecycline- and carbapenem-resistant Klebsiella pneumoniae (TCRKP) is limited. Patients infected with TCRKP were identified from a Taiwanese national surveillance study. Clinical data were collected from medical records. We performed susceptibility tests, carbapenemase gene detection, pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). Furthermore, we performed quantitative real-time polymerase chain reaction (qRT-PCR) analyses to assess the expression levels of the efflux pump genes acrB and oqxB. We identified 16 patients infected with TCRKP, with urinary tract infection (UTI) being the most common type of infection (63%). The all-cause 30-day mortality rate was 44% in patients with TCRKP infection. Patients with a site of infection other than the urinary tract had a significantly higher mortality rate than patients with UTIs (83% vs. 20%, p = 0.035). PFGE and MLST revealed no dominant clone or sequence type. Using qRT-PCR, overexpression of both the acrB and oqxB genes was identified in seven isolates, and overexpression of the oqxB gene was observed in another seven. There was poor correlation between acrB or oqxB expression and tigecycline MICs (r = -0.038 and -0.166, respectively). The mortality rate in patients infected with TCRKP in this study was 44% and this is an important subset of patients. The absence of a linear relationship between efflux pump genes expression and MICs indicates that tigecycline resistance may be mediated by other factors. Continuous monitoring of tigecycline resistance among CRKP isolates and resistance mechanisms are necessary.


Diverticulectomy, myotomy, and fundoplication through laparoscopy: a new option to treat epiphrenic esophageal diverticula?
To describe the technique and the results of laparoscopic diverticulectomy combined with esophageal myotomy and antireflux wrap for epiphrenic diverticula of the esophagus. The epiphrenic diverticulum of the esophagus is a rare disease probably caused by a longstanding impairment of the esophageal motor activity. Although there is almost universal agreement to operate only on symptomatic patients, the optimal treatment is controversial. The best-accepted guideline is to treat the underlying motor disorder. This is generally done through a left thoracotomic approach that allows diverticulectomy, esophageal myotomy, and partial fundoplication. From January 1994 through February 1996, 4 patients underwent laparoscopic transhiatal diverticulectomy, esophageal myotomy, and partial fundoplication at our institution. A thorough preoperative study was done with barium swallow, esophagoscopy, and manometry in all patients; 24-hour pH monitoring was done in one case. No postoperative complications were observed. Short- and medium-term results are satisfactory. No theoretical objection should be made to this approach, because the principle of treatment of the diverticular pouch and the underlying motor disorder and the prevention of reflux is respected. Longer follow-up and a wider series are mandatory to substantiate these initially favorable results.


Discrimination of nonobstructive hypertrophic cardiomyopathy from hypertensive left ventricular hypertrophy on the basis of strain rate imaging by tissue Doppler ultrasonography.
The differentiation of hypertrophic cardiomyopathy (HCM) from hypertensive left ventricular hypertrophy (H-LVH) on the basis of morphological information obtained by conventional echocardiography is occasionally problematic. We investigated whether strain rate (SR) imaging derived from tissue Doppler imaging (TDI) is able to discriminate HCM from H-LVH. Conventional echocardiography and TDI were performed with 34 patients with LVH and 16 reference subjects. Mean values of systolic strain (epsilon(sys)), peak systolic SR, and early diastolic SR obtained from 8 left ventricular (LV) segments were calculated. LV pressures were recorded simultaneously in the patients. Patients were diagnosed with HCM (n=20) or H-LVH (n=14) on the basis of conventional echocardiography and endomyocardial biopsy findings. Multivariate analysis revealed that septum/posterior wall thickness ratio (P=0.00013) and epsilon(sys) (P<0.0001) were each able to discriminate HCM from H-LVH. A epsilon(sys) cutoff value of -10.6% discriminated between HCM and H-LVH with a sensitivity of 85.0%, specificity of 100.0%, and predictive accuracy of 91.2%. The combination of the septum/posterior wall thickness ratio and epsilon(sys) discriminated HCM from H-LVH with a predictive accuracy of 96.1%. The epsilon(sys) parameter was significantly correlated with pulmonary arterial wedge pressure, LV end-diastolic pressure, the peak positive first derivative of LV pressure, and the time constant of LV pressure decay. SR imaging is able to discriminate HCM from H-LVH, with epsilon(sys) reflecting myocardial contractile and lusitropic properties.


Twisting mice move the dystonia field forward.
A common form of the hyperkinetic movement disorder dystonia is caused by mutations in the gene TOR1A (located within the DYT1 locus), which encodes the ATPase torsinA. The underlying neurobiological mechanisms that result in dystonia are poorly understood, and progress in the field has been hampered by the absence of a dystonia-like phenotype in animal models with genetic modification of Tor1a. In this issue of the JCI, Liang et al. establish the first animal model with a dystonic motor phenotype and link torsinA hypofunction to the development of early neuropathological changes in distinct sensorimotor regions. The findings of this study will likely play an important role in elucidating the neural substrate for dystonia and should stimulate systematic neuropathological and imaging studies in carriers of TOR1A mutations.


Potentiation of leukotriene B4-mediated inflammatory response by the adenosine antagonist, 8-phenyl theophylline.
Previous in vitro studies have shown that adenosine (ADO)-induced inhibition of granulocyte function is near maximal at the sub-micromolar concentrations that would be anticipated in normal tissues. If this mechanism is operative in vivo, then antagonizing ADO receptors should potentiate granulocyte-mediated inflammatory responses. To unmask the putative inhibition, the antagonist, 8-phenyl theophylline (8pTHEO), was continuously suffused over the hamster cheek pouch microcirculation, which was observed with intravital bright field and fluorescence microscopy. As an index of inflammation, macromolecular permeability was measured by determining extravasation of fluorescein isothiocyanate-labelled dextran (MW 150,000). In addition, tissue specimens were fixed and stained with hematoxylin and eosin for histological quantification of intravascular and extravascular granulocytes. The tissue was challenged with a 10-40 min topical application of leukotriene B4 (LTB4, 1.1-4nM) or histamine (0.5 or 10 microM) with and without 8pTHEO, at a concentration (8 microM) that attenuated vasodilation evoked by exogenous ADO. These two inflammatory stimuli were chosen because LTB4 evokes a granulocyte-dependent response in the cheek pouch, while histamine evokes a granulocyte-independent response. 8pTHEO potentiated the dose-related increase caused by LTB4 but had no effect on permeability in baseline conditions or on the response evoked by histamine. In baseline conditions, there were fewer than 500 intravascular granulocytes/mm2 microvessel surface area and fewer than 3000 extravascular granulocytes/cm2 tissue surface area. After LTB4 challenge, there was a 3-4 fold increase in the numbers of extra- and intra-vascular granulocytes compared to baseline, but no dose-related relationship could be detected over the concentration range 1.1-4 nM. With 8pTHEO + 1.1 nM LTB4, the granulocyte accumulation was similar to that with LTB4 alone, but there were significantly more intravascular and extravascular granulocytes in the 8pTHEO after 2.5-4 nM LTB4. In context with previous studies, these results suggest that endogenous ADO exerts a tonic inhibitory influence on granulocytes during LTB4 stimulation and this action can be unmasked with methylxanthines.


Computerized neurocognitive test performance in schizophrenia: a lifespan analysis.
Computerized neurocognitive batteries based on advanced behavioral neuroscience methods are increasingly used in large-scale clinical and genomic studies. Favorable construct validity in younger schizophrenia patients has been reported, but not in older patients. New variables afforded by computerized assessments were used to clarify age-associated cognitive impairment across the lifespan. 624 patients with schizophrenia and 624 healthy comparison (HC) subjects age 16-75 completed a 1-2-hour computerized neurocognitive battery (CNB) that assessed abstraction and mental flexibility, attention, working memory, recognition memory (verbal, facial, spatial), language, visuospatial, and emotion processing. Linear mixed effects models tested for group differences in accuracy, response time, and efficiency scores. Contrasts were stratified by age. 91% of older (45+) and 94% of younger (< 45) groups provided "good" data quality. After controlling for parental education and project, there were significant three-way interactions for diagnosis x domain x age group on all three outcome variables. Patients performed worse than HC across all neurocognitive domains, except in the oldest group of 60+ patients. Age-stratified analyses did not show differences between younger (16-45) and older patients (45-60, 60+), except for the attention domain. Older patients' reduced working memory efficiency was due to worse speed, not accuracy. Older patients were quicker than younger patients in processing emotions. Computerized assessments are feasible in large cohorts of schizophrenia patients. There is stable and generalized neurocognitive dysfunction across the lifespan in schizophrenia, albeit with fewer differences in some domains between older patients and HC after age 60. Speed-accuracy tradeoff strategies suggest deceleration of some frontal networks and improvements in speed of emotional processing.


Gene signatures in U-BIOPRED severe asthma for molecular phenotyping and precision medicine: time for clinical use.
The use and generation of gene signatures have been established as a method to define molecular endotypes in complex diseases such as severe asthma. Bioinformatic approaches have now been applied to large omics datasets to define the various co-existing inflammatory and cellular functional pathways driving or characterizing a particular molecular endotype. Molecular phenotypes and endotypes of Type 2 inflammatory pathways and also of non-Type 2 inflammatory pathways, such as IL-6 trans-signaling, IL-17 activation, and IL-22 activation, have been defined in the Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes dataset. There has also been the identification of the role of mast cell activation and of macrophage dysfunction in various phenotypes of severe asthma. Phenotyping on the basis of clinical treatable traits is not sufficient for understanding of mechanisms driving the disease in severe asthma. It is time to consider whether certain patients with severe asthma, such as those non-responsive to current therapies, including Type 2 biologics, would be better served using an approach of molecular endotyping using gene signatures for management purposes rather than the current sole reliance on blood eosinophil counts or exhaled nitric oxide measurements.


Plasma level monitoring of anticonvulsants.
The plasma concentrations of anticonvulsant drugs, and of certain of their biologically active metabolites, tend to be proportionate to the antiepileptic effects of these drugs. Consequently, anticonvulsant drug levels in plasma are monitored to help guide the clinician in managing his patients' epilepsies. In making use of the measurements, the clinician needs to know the relation between plasma level and biological effect for the various drugs. He also needs to have some awareness of simple pharmacokinetic principles. These are important in deciding when plasma levels should be monitored in relation to the patients' clinical state, to the dosage interval, and to change in the dosage of anticonvulsant or other drug. The clinician also requires pharmacokinetic knowledge in altering anticonvulsant drug dosage in his patients, and in interpreting plasma anticonvulsant level data, particularly when the patient is concurrently suffering from non-neurological disease. The ability to monitor plasma anticonvulsant levels has appreciably improved the treatment of epilepsy, but to obtain maximum benefits from the method, both pharmacokinetic insight and clinical wisdom are required.


Pterygodermatites (Mesopectines) senegalensis n. sp. (Nematoda, Rictulariidae), a parasite of Mastomys huberti (Rodentia, Muridae) in Senegal.
Pterygodermatites (Mesopectines) senegalensis n. sp. (Nematoda: Rictulariidae) is described from Mastomys huberti in Senegal. It differs from other species of the subgenus by the morphology of the head, which exhibits 4 simple cephalic papillae and a nearly axial buccal opening, the length of the spicules, the number of precloacal cuticular formations, and the absence of cephalic apophyses.


Generation of human induced pluripotent stem cell line (MUi033-A) from a male with homozygous for Hemoglobin E.
Hemoglobin E (HbE), a common variant in Southeast Asian populations, results from a G to A substitution at codon 26 of the HBB gene, causing abnormal Hb and mild β-thalassemia-like symptoms. Here, we derived an induced pluripotent stem cell (iPSC) line, named MUi033-A, from a male homozygous for HbE. The iPSC line demonstrates a normal karyotype and embryonic stem cell-like properties including pluripotency gene expression, and tri-lineage differentiation potential. This iPSC resource holds the potential for investigating gene therapy targeting HbE mutation.


Impact of Freeze- and Spray-Drying Microencapsulation Techniques on β-Glucan Powder Biological Activity: A Comparative Study.
The study compares the impact of freeze- and spray-drying (FD, SD) microencapsulation methods on the content of β-glucan, total polyphenols (TP), total flavonoids (TF), phenolic acids (PA), and antioxidant activity (AA) in commercially β-glucan powder (Pleurotus ostreatus) using maltodextrin as a carrier. Morphology (scanning electron microscopy- SEM), yield, moisture content (MC), and water activity (aw) were also evaluated in the samples. Our examinations revealed significant structural differences between powders microencapsulated by the drying methods. As compared to non-encapsulated powder, the SD powder with yield of 44.38 ± 0.55% exhibited more reduced (p < 0.05) values for aw (0.456 ± 0.001) and MC (8.90 ± 0.44%) than the FD one (yield: 27.97 ± 0.33%; aw: 0.506 ± 0.002; MC: 11.30 ± 0.28%). In addition, the highest values for β-glucan content (72.39 ± 0.38%), TPC (3.40 ± 0.17 mg GAE/g), and TFC (3.07 ± 0.29 mg QE/g) have been detected in the SD powder. Our results allow for the conclusion that the SD microencapsulation method using maltodextrin seems to be more powerful in terms of the β-glucan powder yield and its contents of β-glucan, TP, and TF as compared to the FD technique.


Describing the male registered nursing workforce toward increasing male representation in professional nursing.
Men are significantly underrepresented in nursing and increasing their numbers should be a priority. To describe the male nursing workforce in terms of size, demographics, education, and work settings. Using data from the 2018 National Sample Survey of Registered Nurses, we performed a secondary descriptive analysis. We find that 9.6% of registered nurses are men. Men are more likely than women to hold an associate degree and clinical doctorates, be nurse anesthetists and supervisors, and work in emergency settings but less likely than females to participate in teaching. To increase male representation in nursing we must simultaneously rearticulate what it means for a job to be "female" while also showing that nursing incorporates many skills and interests traditionally coded as "male." We can also show men that nursing offers appealing employment that can lead to a deeply fulfilling personal and professional life.


Evidence for unmasking of rat brown-adipose-tissue mitochondrial GDP-binding sites in response to acute cold exposure. Effects of washing with albumin on GDP binding.
Rats, previously acclimated to 29 degrees C, were moved into the cold (4 degrees C) for 2 h. Scatchard analysis of GDP binding to the brown-adipose-tissue mitochondria of these animals showed a 2.3-fold increase in the number of high-affinity sites and a 1.5-fold increase in the number of low-affinity sites compared with binding in animals maintained at 29 degrees C. Immunochemical determination showed no increase in the amount of mitochondrial uncoupling protein during this period. This strongly suggests an unmasking of existing GDP-binding sites before a detectable increase in synthesis of uncoupling protein can occur. Washing with albumin increased the number of GDP-binding sites of brown-adipose-tissue mitochondria from both warm-housed and cold-exposed animals to the same extent. This indicates that the effects of washing with albumin and cold exposure are independent and additive.


[Perioperative monitoring using transesophageal echocardiography in a case of endocarditis-related tricuspid valve disease].
The risk of infectious endocarditis is higher for intravenous drug users than for patients with either rheumatic disease or valve prostheses. We report the case of a 33-year-old woman who self-administered opioid drugs parenterally and who developed a clinical picture of infectious endocarditis. Serious involvement of the tricuspid valve developed in the form of vegetation requiring surgical repair, during which transesophageal echocardiography was used for perioperative monitoring.


The genomes of the non-clearing-zone-forming and natural-rubber- degrading species Gordonia polyisoprenivorans and Gordonia westfalica harbor genes expressing Lcp activity in Streptomyces strains.
The latex-clearing protein (Lcp(K30)) from the rubber-degrading bacterium Streptomyces sp. strain K30 is involved in the cleavage of poly(cis-1,4-isoprene), yielding isoprenoid aldehydes and ketones. Lcp homologues have so far been detected in all investigated clearing-zone-forming rubber-degrading bacteria. Internal degenerated oligonucleotides derived from lcp genes of Streptomyces sp. strain K30 (lcp(K30)), Streptomyces coelicolor strain A3(2), and Nocardia farcinica strains IFM10152 and E1 were applied in PCR to investigate whether lcp homologues occur also in the non-clearing-zone-forming rubber-utilizing bacteria Gordonia polyisoprenivorans strains VH2 and Y2K, Gordonia alkanivorans strain 44187, and Gordonia westfalica strain Kb1, which grow adhesively on rubber. The 1,230- and 1,224-bp lcp-homologous genes from G. polyisoprenivorans strain VH2 (lcp(VH2)) and G. westfalica strain Kb1 (lcp(Kb1)) were obtained after screening genomic libraries by degenerated PCR amplification, and their translational products exhibited 50 and 52% amino acid identity, respectively, to Lcp(K30). Recombinant lcp(VH2) and lcp(Kb1) harboring cells of the non-rubber-degrading Streptomyces lividans strain TK23 were able to form clearing zones and aldehydes on latex overlay-agar plates, thus indicating that lcp(VH2) and lcp(Kb1) encode functionally active proteins. Analysis by gel permeation chromatography demonstrated lower polymer concentrations and molecular weights of the remaining polyisoprenoid molecules after incubation with these recombinant S. lividans strains. Reverse transcription-PCR analysis demonstrated that lcp(VH2) was transcribed in cells of G. polyisoprenivorans strain VH2 cultivated in the presence of poly(cis-1,4-isoprene) but not in the presence of sodium acetate. Anti-Lcp(K30) immunoglobulin Gs, which were raised in this study, were rather specific for Lcp(K30) and did not cross-react with Lcp(VH2) and Lcp(Kb1). A lcp(VH2) disruption mutant was still able to grow with poly(cis-1,4-isoprene) as sole carbon source; therefore, lcp(VH2) seems not to be essential for rubber degradation in G. polyisoprenivorans.


The effects of anaesthetic agents on cortical mapping during neurosurgical procedures involving eloquent areas of the brain.
In patients presenting for surgical resection of lesions involving, or adjacent to, the functionally important eloquent cortical areas, it is vital to achieve complete or near complete resection of the pathology without damaging the healthy surrounding tissues.The eloquent areas that the surgeons are concerned with are the primary motor, premotor cortex, supplementary motor cortex and speech areas. If the lesions are within these regions surgeons could either take a biopsy or do a intracapsular decompression without damaging the mentioned areas to avoid postoperative dysfunction. If the lesions are adjacent to the above mentioned areas, the normal anatomy would get distorted. However, proper identification of the above mentioned areas would enable the surgeon to radically remove the tumours. Intraoperative mapping of the cortex with stimulating and recording electrodes is termed as electrophysiological (EP) mapping.The EP mapping of motor, sensory and language cortex is widely employed in the resection of lesions involving or adjacent to the eloquent areas. Both intravenous and inhalational agents are known to affect these EP mapping techniques. The aim of this review was to evaluate the effect of anaesthetic agents on intra-operative EP mapping in patients undergoing neurosurgical procedures involving, or adjacent to, the functional areas of the cortex under general anaesthesia. We searched the Cochrane Epilepsy Group Specialized Register (7 March 2011), The Cochrane Central Register of Controlled Trials (CENTRAL issue 1 of 4, The Cochrane Library 2011), MEDLINE (Ovid, 1948 to February week 4, 2011), PsycINFO (EBSCOhost, 7 March 2011), and the National Research Register Archive and UK Clinical Research Network (7 March 2011). We also contacted other researchers in the field in an attempt to ascertain unpublished studies. We planned to include randomised and quasi randomised controlled trials irrespective of blinding in patients of any age or gender undergoing neurosurgery under general anaesthesia where cortical mapping was attempted to identify eloquent areas using either somatosensory evoked potentials (SSEPs), or direct cortical stimulation (DCS) triggered muscle motor evoked potentials (mMEPs), or both. We excluded patients from trials where the anaesthetic effects were evaluated during spinal cord surgery or where MEPs were recorded from modes other than direct cortical stimulation such as transcranial electrical stimulation (TcMEPs), MEPs derived from epidural electrodes (D waves) and magnetic stimulation and trials involving awake craniotomies or the asleep-awake-asleep technique during cortical mapping. Two review authors planned to independently apply the inclusion criteria and extract data. No RCTs were found for this study population. This review highlights the need for well-designed randomised controlled trials to assess the effect of anaesthetic agents on cortical mapping during neurosurgical procedures involving eloquent areas of the brain.


From Yeast to Mammals, the Nonsense-Mediated mRNA Decay as a Master Regulator of Long Non-Coding RNAs Functional Trajectory.
The Nonsense-Mediated mRNA Decay (NMD) has been classically viewed as a translation-dependent RNA surveillance pathway degrading aberrant mRNAs containing premature stop codons. However, it is now clear that mRNA quality control represents only one face of the multiple functions of NMD. Indeed, NMD also regulates the physiological expression of normal mRNAs, and more surprisingly, of long non-coding (lnc)RNAs. Here, we review the different mechanisms of NMD activation in yeast and mammals, and we discuss the molecular bases of the NMD sensitivity of lncRNAs, considering the functional roles of NMD and of translation in the metabolism of these transcripts. In this regard, we describe several examples of functional micropeptides produced from lncRNAs. We propose that translation and NMD provide potent means to regulate the expression of lncRNAs, which might be critical for the cell to respond to environmental changes.


[Bleaching of nonvital teeth].
The bleaching of non vital teeth that is described in this article has demonstrated to give good clinical results, and because of its easy way to apply we believe that it is the option for the treatment of this teeth, as long as we have a good an realistic diagnostic considering the results we may obtain. One the selection has been made we proceed to the bleaching, the substances that we use are easily obtain, superoxol and sodium perborate. The preparation of the tooth began with the removal of any restauration or decayed tissue that is may present after this we remove the material from the pulp chamber 1 mm below the gingival margin, then clean perfectly the chamber, then we deshidrate the tubulae, then put a pellet of cotton on the vestibular wall of the chamber, put some superoxol in the cotton, heat it up, remove the cotton, put some sodium perborate and hidroge peroxide paste in the chamber and seal it with cavit, and wait from 3 to 7 days for results.


[A case report of sinonasal tumor: the effect of corrective make up training].
Facial appearance is very important for personal identity, and some patients suffer long-term stress as a result of disfigurement caused by facial nerve paralysis and wounds. The psychological aspect of the disease has important implications for the optimal management of patients. In such cases, while aggressive rehabilitation including cosmetic surgery may be useful, cosmetics are also effective for covering visible signs of the disease. A patient who had undergone an operation for a sinonasal tumor was instructed by an expert beautician in the application of make up to correct her facial imbalance and wounds. The 60-item General Health Questionnaire (GHQ60) and the European quality of life 5 dimensions (EQ-5D) VAS were administered before the first application and one month afterwards. The GHQ60 and EQ-5D VAS scores improved after the make up instruction. We suggest that corrective make up training is an effective measure for reducing the psychological load of patients with head and neck tumors.


Antibacterial and synergistic effects of the n-BuOH fraction of Sophora flavescens root against oral bacteria.
The antibacterial activity of an extract and several fractions of Sophora flavescens (S. flavescens) root alone and in combination with antibiotics against oral bacteria was investigated by checkerboard assay and time-kill assay. The minimum inhibitory concentration/minimum bactericidal concentration (MIC/MBC) values for all examined bacteria were 0.313-2.5/0.625-2.5 μg/mL for the n-BuOH fraction, 0.625-5/1.25-10 μg/mL for the EtOAc fraction, 0.25-8/0.25-16 μg/mL for ampicillin, 0.5-256/1-512 μg/mL for gentamicin, 0.008-32/0.016-64 μg/mL for erythromycin, and 0.25-64/0.5-128 μg/mL for vancomycin. The n-butanol (n-BuOH) and ethyl acetate (EtOAc) fractions exhibited stronger antibacterial activity against oral bacteria than other fractions and extracts. The MICs and MBCs were reduced to between one half and one quarter when the n-BuOH and EtOAc fractions were combined with antibiotics. After 24 h of incubation, combination of 1/2 MIC of the n-BuOH fraction with antibiotics increased the degree of bactericidal activity. The present results suggest that n-BuOH and EtOAc extracts of S. flavescens root might be applicable as new natural antimicrobial agents against oral pathogens.


[Life cannot consist of dreams alone: reflections on advertising and a healthy diet].
In this essay we present some thoughts on advertising and a healthy diet in the contemporary world, where consumption plays a highly relevant role. We seek to emphasize two aspects, among many others yet to be explored in the scientific literature in the food and nutritional field: the hegemony of the biomedical paradigm and the fragmentation of human life when advertising campaigns associate food with the idea of a healthy diet. We believe that we cannot merely live through advertisements in which our desires are triggered constantly and where the world is only dreams and the main goal is to sell more and earn more, even using some strategies for dissemination of biomedical and nutritional information. In our opinion, the merger between diet and health, i.e. a healthy diet, must involve enlightenment of the individual including information on quality in the context of social life in order to achieve the ideal of happiness. Individuals whose identities are fully formed both in dreams and reality can boldly seek knowledge and think about themselves in the world context, as well as zeal for their diet and health.


Chemokine CXCL10 at week 4 of treatment predicts sustained virological response in patients with chronic hepatitis C.
The aim of this study was to analyze the predictive value of CXCL9, CXCL10, and CXCL11 concentrations before and after 4 and 12 weeks of treatment with pegylated interferon-α2b and ribavirin in patients with chronic hepatitis C infected with the hepatitis C virus genotype 1. The study included 46 adult patients (29 women and 17 men). Chemokine quantification in the serum was performed at baseline and after 1, 3, and 6 months of treatment by enzyme immunoassay. Chemokine responses were compared in patients achieving a sustained virological response to treatment (SVR, n=26) and the non-SVR group (n=20). The differences in the CXCL9 and CXCL10 concentrations between the SVR and non-SVR groups were statistically significant. A multivariant analysis showed a significant association between treatment failure and higher concentrations of CXCL10. A higher predictive value of CXCL10 concentrations after 4 weeks of treatment compared to pretreatment values has been found (area under the curve 0.9288 and 0.7942, respectively, P=0.016). CXCL10 concentrations above 250 pg/mL 4 weeks after the start of treatment were independently associated with non-SVR. In conclusion, the results of this study have shown that CXCL10 concentrations at the time of a rapid viral response (4 weeks) are better predictors of achieving SVR compared to baseline levels. Additionally, this study suggests an important role of CXCL9 as a biomarker of SVR in patients with chronic hepatitis C.


Diversity in pathogenicity can cause outbreaks of meningococcal disease.
Neisseria meningitidis, the meningococcus, is a major cause of bacterial meningitis and septicemia worldwide. Infection in most cases leads to asymptomatic carriage and only rarely to disease. Meningococcal disease often occurs in outbreaks, which are both sporadic and highly unpredictable. The occurrence of disease outbreaks in a host population in which the etiological agent is widely carried is not well understood. A potential explanation lies in the fact that meningococci are diverse with respect to disease-causing potential. We formulated a stochastic mathematical model to investigate whether diversity of the bacterial population is related to outbreaks of meningococcal disease. In the model, strains that occasionally cause the disease appear repeatedly in a population dominated by a nonpathogenic strain. When the pathogenicity, i.e., the disease-causing potential, of the pathogenic lineage was low, the model shows distinct outbreaks, the size distribution of the outbreaks follows a power law, and the ratio of the variance to the mean number of cases is high. Analysis of notification data of meningococcal disease showed that the ratio of the variance to the mean was significantly higher for meningococcal diseases than for other bacterial invasive diseases. This result lends support to the hypothesis that outbreaks of meningococcal disease are caused by diversity in the pathogenicity of meningococcal strains.


The sensory strength of voluntary visual imagery predicts visual working memory capacity.
How much we can actively hold in mind is severely limited and differs greatly from one person to the next. Why some individuals have greater capacities than others is largely unknown. Here, we investigated why such large variations in visual working memory (VWM) capacity might occur, by examining the relationship between visual working memory and visual mental imagery. To assess visual working memory capacity participants were required to remember the orientation of a number of Gabor patches and make subsequent judgments about relative changes in orientation. The sensory strength of voluntary imagery was measured using a previously documented binocular rivalry paradigm. Participants with greater imagery strength also had greater visual working memory capacity. However, they were no better on a verbal number working memory task. Introducing a uniform luminous background during the retention interval of the visual working memory task reduced memory capacity, but only for those with strong imagery. Likewise, for the good imagers increasing background luminance during imagery generation reduced its effect on subsequent binocular rivalry. Luminance increases did not affect any of the subgroups on the verbal number working memory task. Together, these results suggest that luminance was disrupting sensory mechanisms common to both visual working memory and imagery, and not a general working memory system. The disruptive selectivity of background luminance suggests that good imagers, unlike moderate or poor imagers, may use imagery as a mnemonic strategy to perform the visual working memory task.


The place of positive end expiratory pressure in ventilator-induced lung injury generation.
Describe the rationale for concern and accumulating pathophysiologic evidence regarding the adverse effects of high-level positive end expiratory pressure (PEEP) on excessive mechanical stress and ventilator-induced lung injury (VILI). Although the inclusion of PEEP in numerical estimates of mechanical power may be theoretically debated, its potential to increase stress, strain, and mean airway pressure are not. Recent laboratory data in a variety of animal models demonstrate that higher levels of PEEP coupled with additional fluids needed to offset its impediment of hemodynamic function are associated with increased VILI. Moreover, counteracting end-tidal hyperinflation by external chest wall pressure may paradoxically improve respiratory mechanics, indicating that lower PEEP helps protect the small 'baby lung' of advanced acute respiratory distress syndrome (ARDS). The potentially adverse effects of PEEP on VILI can be considered in three broad categories. First, the contribution of PEEP to total mechanical energy expressed through mechanical power, raised mean airway pressure, and end-tidal hyperinflation; second, the hemodynamic consequences of altered cardiac loading, heightened pulmonary vascular stress and total lung water; and third, the ventilatory consequences of compromised carbon dioxide eliminating efficiency. Minimizing ventilation demands, optimized body positioning and care to avoid unnecessary PEEP are central to lung protection in all stages of ARDS.


[Lipoprotein (a) as a risk factor for coronary artery disease in women and elderly patients].
The role of lipoprotein (a) [Lp(a)] as a risk factor for coronary artery disease (CAD) in women and elderly is not clear. In this study we assessed the relation between serum Lp (a) levels and CAD, taking into account the differences in sex and age. Lp (a) levels and other lipid variables were determined in 535 consecutive patients undergoing coronary angiography for chest pain evaluation. Among 535 patients, 163 patients had angiographically normal coronary arteries (70 men and 93 women) and 372 patients had significant coronary lesions at least one coronary artery (300 men and 72 women). After adjustment for hypertension, smoking, diabetes, low density lipoprotein-cholesterol (LDL-C), triglycerides and high density lipoprotein-cholesterol (HDL-C), elevated Lp (a) was independently predictive for CAD in both sexes under 55 years old (odds ratio [OR]: 5.1, p < 0.01 for men and OR: 2.3, p < 0.05 for women). In patients more than 55 years old elevated Lp (a) was not associated with CAD for both sexes (OR: 1.3, p = NS for men and OR: 1.2, p = NS for women). We did not find any relation between elevated Lp (a) concentrations and presence of angiographically detectable CAD both in men and women aged more than 55 years old. Our results suggest that elevated Lp (a) is an independent risk factor for premature CAD for both men and women.


[The clinical results and lipid peroxidation dynamics in the patients presenting with psoriasis treated by the applications of a natural highly mineralized bromine-iodine brine].
The authors report the results of the treatment of 64 patients presenting with psoriasis by the applications of a natural highly mineralized bromine-iodine brine. The method has been shown to be highly efficacious and safe. It allowed the clinical remission and marked improvement of the patients' clinical conditions to be achieved in 48 (77.4%) cases compared with 10 (27.8%) cases among the patients of the control group. Exacerbation was documented in a single patient with psoriatic erythrodermia. All the patients showed the normal results of general and biochemical clinical analyses of blood and urea throughout the study period. The applications of the natural highly mineralized bromine-iodine brine exerted the normalizing action on seven of the 8 characteristics of the lipid peroxidation process. It is maintained that the high effectiveness of the method in question can be accounted not only by the reflectory and humoral mechanisms of action of highly mineralized bromine-iodine brine but also by the marked exhaustion of the functional reserves of the mast cells under effect of the applications. It is concluded that an advantage of the proposed approach over standard balneotherapeutic procedures consists of the possibility to employ it not only at the base of a spa and health resort facility but also in a different setting with the involvement of the patients suffering from progressive psoriasis.


An evaluation of universal health insurance in the elderly: burden of disease, utilization, and costs in the Republic of Korea.
This article evaluates Korea's national health insurance system for the elderly by simultaneously examining disease patterns, demand for care, utilization, costs of care, and facility type. Claim records (N = 8,306,976) for 1995 to 1997 were obtained from the Youndeoung-Po district for four insurance categories. Utilization is examined using a probit model; a linear regression model is used to compare costs. Insurees averaged 10.6 medical visits per year, most commonly for acute respiratory diseases. The elderly were more likely to seek care for circulatory problems, use more inpatient services, and rely on hospitals for outpatient care. Insurance costs for the elderly poor were markedly higher, and overall care for the elderly was higher per visit. By simultaneously analyzing utilization rates, disease patterns, and relative costs of care, policymakers may be able to avert a financing crisis. Stronger pricing strategies and better disease targeting would adjust utilization and increase efficiency of health expenditures.


Positively charged gelatin microspheres as gastric mucoadhesive drug delivery system for eradication of H. pylori.
Gastric mucoadhesive drug delivery systems are very promising for eradication of Helicobacter pylori (H. pylori), a spiral bacterium that resides in the gastric mucus layer and at the mucus-epithelial cell interface. New positively charged biodegradable microspheres were prepared using aminated gelatin by surfactant-free emulsification in olive oil, followed by a cross-linking reaction with glutaraldehyde. The amino group contents of the modified gelatin and the microspheres were determined using a 2,4,6-trinitrobenzenesulfonic acid method. With the increase of glutaraldehyde concentration, the amino group content of the microspheres decreased accordingly. The influence of glutaraldehyde concentration, cross-linking reaction time, drug-loading patterns, and type of release media on the in vitro release characteristics of amoxicillin from the microspheres was investigated. Amoxicillin release rate from the modified gelatin microspheres was significantly reduced compared with that from gelatin microspheres. Furthermore, the release was decreased with the increase of glutaraldehyde concentration and/or cross-linking time. On the other hand, a faster release was observed in a lower pH release medium and/or using a lower pH solution for amoxicillin loading. The gastric mucoadhesive properties of the microspheres were evaluated using RITC-labeled microspheres in an isolated rat stomach. The gastric mucoadhesion of the modified gelatin microspheres was markedly improved compared with that of gelatin microspheres. The modified gelatin microsphere proves to be a possible candidate delivery system for the effective eradication of H. pylori.


Trajectories of Blood Lipids Profile in Midlife Women: Does Menopause Matter?
Background It remains controversial whether changes of lipids over menopause transition (MT) are more age-related or more menopause-related. We aimed to classify women into different trajectory groups based on pattern and level of total cholesterol, low-density lipoprotein cholesterol, apolipoprotein B (ApoB), high-density lipoprotein cholesterol (HDL-C), triglyceride, and apolipoprotein A-I over the MT, as well as examine the effect of MT-related factors on lipid trajectory groups and levels. Methods and Results The cohort included 2582 subjects from the Study of Women's Health Across the Nation. Different trajectory patterns of lipids during the MT were determined using the latent class growth mixture model. The predictors of distinct blood lipids trajectory groups were determined by multiple linear regression models and multinomial logistic regression models. Women were categorized into either inverse U-shape or progressing trajectory group in each blood lipids measurement. The inverse U-shape total cholesterol, low-density lipoprotein cholesterol, apolipoprotein B, high-density lipoprotein cholesterol, log(TG), and apolipoprotein A-I trajectories showed an increasing trend before menopause but a decreasing trend after menopause. The U-shape total cholesterol, low-density lipoprotein cholesterol, and apolipoprotein B trajectories started to rise 5 years before menopause. Age at menopause, follicle-stimulating hormone, vasomotor symptoms, and estradiol predicted the shape and level of the women's lipids over the MT. Conclusions Distinct lipid trajectories were identified during the MT, and the existence of at least 1 trajectory in each lipid parameters suggested a contribution of menopause. Our study highlights the need for earlier and continuous surveillance of lipids during the MT.


[Peculiarities of mortmass mycobiota formation in soft-deciduous young forests on old-tillage soils of the Chernihiv Polissya].
Thirty eight species of fungi were identified as a result of mycological analysis of 180 mortmass samples of Betulapendula Routh. and Populus tremula L. Mortmass mycobiota of B. pendula and P. tremula was represented by white, brown- and soft-rot species. Fungi of Ascomycota phylum were most numerous (24 species). Species of genera Aspergillus, Penicillium, Brachysporium, Cladosporium, Drechslera, Fusarium, Cylindrocarpon, Spadicesporium, Trichoderma in variants with middle and hard classes of wood degradation were identified among them. The Basidiomycota phylum was represented by 12 species; among them Armillariella mellea and Phellinus igniarius occurred most frequently. The most specific fungal complex decaying B. pendula and P tremula mortmass was observed under class III of its degradation.


Hierarchically controllable photoreaction of a coordination polymer based on quaternized 1,2-bis(4'-pyridyl)ethylene.
A multiply photoactive compound has been developed based on quaternized 1,2-bis(4'-pyridyl)ethylene, which exhibits a hierarchical photoreaction by controlling light intensity. Weak ultraviolet light can effectively promote the cycloaddition reaction with fluorescence enhancement, while stronger ultraviolet light can stimulate a complex response of cycloaddition and electron-transfer which shows turn-off luminescence and coloration. Photofacilitated bleaching of the colored products has been observed for the first time in the pyridinium family.


Cellular localization and effect of nitric oxide synthesis in a rat model of orthotopic liver transplantation.
Nitric oxide (NO) is a multifunctional free radical with a variety of described biochemical and physiological roles. The immunologic relationships between organ transplantation and NO synthesis are unknown. While a number of in vitro and in vivo models have demonstrated an immunomodulatory role for NO, results suggest both an immunosuppressive and immunostimulatory function. In order to better delineate the role of NO in liver transplantation, the Kamada model of rat OLT with strain combinations simulating acute rejection and spontaneous hyporesponsiveness was chosen. In this setting, both acute rejection and spontaneous hyporesponsiveness were associated with increased levels of plasma NO metabolites and allograft expression of the enzyme, NO synthase (iNOS). The extent of expression was significantly greater with acute rejection. Using in situ hybridization, iNOS mRNA was localized to both infiltrating inflammatory cells and hepatocytes in the context of acute rejection. In contrast, iNOS mRNA expression was isolated to the hepatocytes in the hyporesponsive state. To specifically delineate the role of hepatocyte-derived NO, NO synthesis was ablated in the spontaneous hyporesponsiveness model and resulted in significant elevation of serum transaminase values with accompanying histologic evidence of increased periportal inflammatory infiltration. Our results suggest that the site of NO production varies according to the immunologic status of the liver allograft, and hepatocyte-derived NO may be protective in the hyporesponsive state.


Management of suspected venous thromboembolism: the impact of a multifaceted intervention.
To achieve a common strategy in the event of a suspected venous thromboembolism. A multifaceted intervention, combining an audit strategy and implementation of local guidelines: phase 1, the first step, consisted of a 6-month audit to identify dysfunction; during phase 2, intervention, local guidelines were formulated by a working group and then implemented; phase 3 consisted of a re-audit over a 6-month period following the intervention. A tertiary hospital, France. 419 patients with suspected venous thromboembolism in phase 1; 287 patients with suspected pulmonary embolism in phase 3. First phase: a dysfunction was observed in three of five criteria under study: (i) the diagnostic procedure lasted more than 48 hours in 114 patients (27.2%); (ii) no anticoagulant therapy at the time of suspicion in 116 patients (27.7%); (iii) an inconclusive lung scan without further testing in the event of a suspected pulmonary embolism in 40 patients (14%); the intervention phase was thus restricted to the management of suspected pulmonary embolism; similar results were found during the phase 3 re-audit. No improvement in the diagnostic work-up in the event of a suspected pulmonary embolism was observed following this multifaceted intervention.


Bowel-bypass syndrome without bowel bypass. Bowel-associated dermatosis-arthritis syndrome.
A recurrent, episodic illness that occurs in as many as 20% of patients who undergo ileojejunal bypass surgery for morbid obesity has been well characterized and includes inflammatory cutaneous lesions with a histologic appearance like that of neutrophilic vasculitis, a nondeforming polyarthritis, and other systemic manifestations. Current concepts of pathogenesis center on overgrowth of bacterial flora in the bypassed bowel segment with subsequent development of a circulating immune complex disease. We report, for the first time to our knowledge, an identical clinicopathologic syndrome in four patients who have not had jejunoileal bypass surgery. Each patient, however, had other gastrointestinal disease that we believe predisposed to this syndrome, possibly via circulating immune complexes with bowel-associated antigens. We propose the expanded term, bowel-associated dermatosis-arthritis syndrome, to incorporate these new cases. We believe that this is not a rare syndrome and that it is easily distinguishable from other types of cutaneous necrotizing vasculitis.


Gradient-based residual variance modeling and its applications to motion-compensated video coding.
This paper analyzes the relationship between the residual frame and the previous frame in motion-compensated video coding. It is found that the variance of the residual signal depends on the gradient magnitude. On average, the variance of the residual signal is larger for pixels with larger gradient magnitude. Two applications of this analysis are presented. In the first one, the relationship between the residual signal variance and the gradient magnitude is used to model the second-order statistics of the residual field in a nonstationary way. This modeling enables more efficient residual signal coding. The other application is for pixel decimation-based fast block matching. It is proposed that pixels with the largest gradient magnitude in a block be chosen to participate in the block matching process. It is demonstrated that such a gradient-adaptive subsampling achieves great advantage over two other known subsampling methods.


The retinoic acid hydroxylase Cyp26a1 has minor effects on postnatal vitamin A homeostasis, but is required for exogenous atRA clearance.
The all-trans-retinoic acid (atRA) hydroxylase Cyp26a1 is essential for embryonic development and may play a key role in regulating atRA clearance also in adults. We hypothesized that loss of Cyp26a1 activity via inducible knockout in juvenile or adult mice would result in decreased atRA clearance and increased tissue atRA concentrations and atRA-related adverse effects. To test these hypotheses, Cyp26a1 was knocked out in juvenile and adult male and female Cyp26a1 floxed mice using standard Cre-Lox technology and tamoxifen injections. Biochemical and histological methods were used to study the effects of global Cyp26a1 knockout. The Cyp26a1 knockout did not result in consistent histopathological changes in any major organs. Cyp26a1-/- mice gained weight normally and exhibited no adverse phenotypes for up to 1 year after loss of Cyp26a1 expression. Similarly, atRA concentrations were not increased in the liver, testes, spleen, or serum of these mice, and the Cyp26a1 knockout did not cause compensatory induction of lecithin:retinol acetyltransferase (Lrat) or retinol dehydrogenase 11 (Rdh11) mRNA or a decrease in aldehyde dehydrogenase 1a1 (Aldh1a1) mRNA in the liver compared with tamoxifen-treated controls. However, the Cyp26a1-/- mice showed increased bone marrow cellularity and decreased frequency of erythroid progenitor cells in the bone marrow consistent with a retinoid-induced myeloid skewing of hematopoiesis. In addition, the Cyp26a1 knockout decreased clearance of exogenous atRA by 70% and increased atRA half-life 6-fold. These findings demonstrate that despite lacking a major impact on endogenous atRA signaling, Cyp26a1 critically contributes as a barrier for exogenous atRA exposure.


Fatigue in childhood chronic disease.
Recently, in adults, the incidence and severity of fatigue was found to exist rather independently from the somatic diagnosis. Since fatigue is distressing when growing up with a chronic disease, we aim to investigate: (1) the prevalence and extent of fatigue among various paediatric chronic diseases and (2) the effect of fatigue on health-related quality of life (HRQoL). Cross-sectional study in two children's hospitals. Children and adolescents 2-18 years of age with cystic fibrosis, an autoimmune disease or postcancer treatment visiting the outpatient clinic. Fatigue and HRQoL were assessed using the Pediatric Quality of Life Inventory (PedsQL) multidimensional fatigue scale (with lower scores indicating more fatigue) and PedsQL generic core scales, respectively. Linear regression analysis and analysis of covariance were used to compare fatigue scores across disease groups and against two control groups. The effect of fatigue on HRQoL was calculated. Data were adjusted for age, sex and reporting method. 481 children and adolescents were assessed (60% participation rate, mean age 10.7±4.9, 42% men). Children and adolescents with chronic disease reported more fatigue than the general population (mean difference -6.6, 95% CI -8.9 to -4.3 (range 0-100)), with a prevalence of severe fatigue of 21.2%. Fatigue scores did not differ significantly between disease groups on any fatigue domain. Fatigue was associated with lower HRQoL on all domains. Fatigue in childhood chronic disease is a common symptom that presents across disease, age and sex groups. Fatigue affects HRQoL. Our findings underscore the need to systematically assess fatigue. Future studies should determine possible biological and psychosocial treatment targets.


Physical and chemical modifications of adriamycin:iron complex by phospholipid bilayers.
Adriamycin (ADM) and the ADM:Fe(III) complex both interact with phosphatidylcholine bilayers in aqueous vesicle dispersions. The immediate interaction of either ADM or ADM:Fe(III) with phospholipid causes little change in their absorption or emission spectra, but considerably increases the steady-state fluorescence anisotropy of both species. This is followed by a conversion of the ADM:Fe(III) complex (but not of metal-free ADM) into a new compound in periods ranging from minutes to hours depending upon the Fe(III) concentration. This reaction does not require the presence of unsaturated acyl chains, net negatively charged phospholipid head groups, or the participation of molecular oxygen. This new compound has a characteristic absorption and fluorescence emission spectra which differ from those of the ADM:Fe(III) or of metal-free ADM. It can be isolated from the aqueous lipid dispersion by Folch extraction under acidic conditions. It is very lipophilic in comparison to ADM or the ADM:Fe(III) complex. It may be similar to the compound reported to form between cardiolipin and Adriamycin. Preliminary results indicate that it also forms spontaneously in intact biological membranes. Its highly lipophilic character may confine it to bilayers and membranes.


Associations between GSTM1 and OGG1 Ser326Cys polymorphisms and smoking on chromosomal damage and birth growth in mothers.
The presenting study was investigated the associations between individual susceptibility and cigarette smoke on maternal chromosomal damage and neonatal birth growth in smoking mothers since little known about genetic susceptibility to cigarette smoke in relation to adverse pregnancy outcome such as birth growth. Sixty-one pregnant women who completed a questionnaire at Ankara Education and Research Hospital, Department of Obstetrics and Gynecology have enrolled in this study. GSTM1 and OGG1 ser326Cys gene polymorphisms were analysed by RFLP-PCR (Restriction Fragment Length Polymorphism-Polymerase Chain Reaction) as possible genetic factors affecting susceptibility to such health effects of smoking and chromosomal damage was performed by chromosomal aberration assay (CAA) in maternal blood lymphocytes. Maternal self-reported history of pregnancy smoking was informed by questionnaire declaration. Our results showed that maternal smoking had significant effect on chromosomal damage, birth weight, and length. The frequencies of CA in smokers was significantly higher than that of the nonsmokers (3.46 ± 2.06 and 2.00 ± 1.3, P = 0.001). Birth weight and length in smokers were significantly higher that of nonsmokers (3,355 g and 49.57 cm, P = 0.001; 3,639 g and 50.79 cm, P = 0.002). On the other hand, there was a slightly increased in the frequencies of CA and reduction birth weight and length in GSTM1 null and length in OGG1 variant genotypes, those differences were not statistically significant (P > 0.05); likely due to small sample size. Larger sample size needs to reach significance.


Normal values of the Foot Posture Index in a young adult Spanish population: a cross-sectional study.
Although the appearance of foot or lower-limb pathologies is etiologically multifactorial, foot postures in pronation or supination have been related to certain diseases such as patellofemoral syndrome and plantar fasciitis. The objective of the present study was to determine the normal values of foot posture in a healthy young adult Spanish sample, and to identify individuals at risk of developing some foot pathology. The Foot Posture Index (FPI) was determined in a sample of 635 (304 men, 331 women) healthy young adults (ages 18-30 years). The FPI raw score was transformed into a logit score, and a new classification was obtained with the mean ± 2 SD to identify the 5% of the sample with potentially pathologic feet. The normal range of the FPI was -1 to +6, and FPI values from +10 to +12 and -6 to -12 could be classified as indicating potentially pathologic feet. The women's logit FPI (0.50 ± 1.4, raw FPI +3) was higher than the men's (0.25 ± 1.6, raw FPI +2), with the difference being significant (P = 0.038). No statistically significant differences were found between body mass index groups (P = 0.141). The normal FPI range goes from just one point of supination to a certain degree of pronation (+6). The identification of 35 individuals with potentially pathologic feet may help in the implementation of a preventive plan to avoid the appearance of foot disorders.


Recessive lethal amber suppressors in yeast.
Recessive lethal amber suppressor mutations have been isolated in a diploid strain of Saccharomyces cerevisiae. Diploids carrying these suppressors upon sporulation yield asci with only two live spores, both lacking the suppressor. At least two classes of recessive lethal suppressors exist. Aneuploid strains carrying one wild type and one suppressor locus have been isolated and used in mapping studies; one suppressor maps on chromosome III, the other does not.


Representative Data Selection for Efficient Medical Incremental Learning.
To train a deep neural network relies on a large amount of annotated data. In special scenarios like industry defect detection and medical imaging, it is hard to collect sufficient labeled data all at once. Newly annotated data may arrive incrementally. In practice, we also prefer our target model to improve its capability gradually as new data comes in by quick re-training. This work tackles this problem from a data selection prospective by constraining ourselves to always retrain the target model with a fix amount of data after new data comes in. A variational autoencoder (VAE) and an adversarial network are combined for data selection, achieving fast model retraining. This enables the target model to continually learn from a small training set while not losing the information learned from previous iterations, thus incrementally adapting itself to new-coming data. We validate our framework on the LGG Segmentation dataset for the semantic segmentation task.Clinical relevance- The proposed VAE-based data selection model combined with adversarial training can choose a representative and reliable subset of data for time-efficient medical incremental learning. Users can immediately see the improvement of the medical segmentation model whenever new annotated images are contributed (after a few minutes of model retraining).


Clinical implications of the BARI 2D and COURAGE trials: the evolving role of percutaneous coronary intervention.
This review outlines the evolving role of percutaneous coronary intervention (PCI) for stable angina in the context of the widely discussed Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) and Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trials. Factors outlined include defining the appropriate patient population, the clinical circumstances, and the technical aspects of the procedure to optimize clinical outcomes and minimize risk. The COURAGE Trial, as others reported earlier, reported no difference in death or myocardial infarction with PCI compared with medical therapy for stable angina. In patients with type 2 diabetes mellitus in the BARI 2D Trial, a strategy of revascularization with coronary artery bypass graft surgery (CABG) or PCI resulted in no difference in mortality compared with optimal medical therapy. However, PCI for stable angina was associated with reduced angina and improved quality of life. Procedural aspects of PCI that support its continuing role in the management of patients with stable angina include the frequent advancements in PCI technology that have further enhanced both acute and long-term success. In conclusion, the implications of these findings for clinical practice include evaluating the use of PCI for stable angina in addition to optimal medical therapy to reduce angina and improve quality of life, but individualizing care for higher risk patients with more complex coronary artery disease who were not enrolled in the COURAGE and BARI 2D trials.


Surface functionalization of a polymeric lipid bilayer for coupling a model biological membrane with molecules, cells, and microstructures.
We describe a stable and functional model biological membrane based on a polymerized lipid bilayer with a chemically modified surface. A polymerized lipid bilayer was formed from a mixture of two diacetylene-containing phospholipids, 1,2-bis(10,12-tricosadiynoyl)-sn-glycero-3-phosphocholine (DiynePC) and 1,2-bis(10,12-tricosadiynoyl)-sn-glycero-3-phosphoethanolamine (DiynePE). DiynePC formed a stable bilayer structure, whereas the ethanolamine headgroup of DiynePE enabled functional molecules to be grafted onto the membrane surface. Copolymerization of DiynePC and DiynePE resulted in a robust bilayer. Functionalization of the polymeric bilayer provided a route to a robust and biomimetic surface that can be linked with biomolecules, cells, and three-dimensional (3D) microstructures. Biotin and peptides were grafted onto the polymeric bilayer for attaching streptavidin and cultured mammalian cells by molecular recognition, respectively. Nonspecific adsorption of proteins and cells on polymeric bilayers was minimum. DiynePE was also used to attach a microstructure made of an elastomer (polydimethylsiloxan: PDMS) onto the membrane, forming a confined aqueous solution between the two surfaces. The microcompartment enabled us to assay the activity of a membrane-bound enzyme (cyochrome P450). Natural (fluid) lipid bilayers were incorporated together with membrane-bound proteins by lithographically polymerizing DiynePC/DiynePE bilayers. The hybrid membrane of functionalized polymeric bilayers and fluid bilayers offers a novel platform for a wide range of biomedical applications including biosensor, bioassay, cell culture, and cell-based assay.


Psychometric properties of the Depression Anxiety and Stress Scale-21 in older primary care patients.
The Depression Anxiety Stress Scale (DASS) was designed to efficiently measure the core symptoms of anxiety and depression and has demonstrated positive psychometric properties in adult samples of anxiety and depression patients and student samples. Despite these findings, the psychometric properties of the DASS remain untested in older adults, for whom the identification of efficient measures of these constructs is especially important. To determine the psychometric properties of the DASS 21-item version in older adults, we analyzed data from 222 medical patients seeking treatment to manage worry. Consistent with younger samples, a three-factor structure best fit the data. Results also indicated good internal consistency, excellent convergent validity, and good discriminative validity, especially for the Depression scale. Receiver operating curve analyses indicated that the DASS-21 predicted the diagnostic presence of generalized anxiety disorder and depression as well as other commonly used measures. These data suggest that the DASS may be used with older adults in lieu of multiple scales designed to measure similar constructs, thereby reducing participant burden and facilitating assessment in settings with limited assessment resources.


Rapid method for detection of mutations in the nucleophosmin gene in acute myeloid leukemia.
Mutations in exon 12 of the nucleophosmin gene (NPM1) that cause the encoded protein to abnormally relocate to the cytoplasm are found at diagnosis in about 50% of karyotypically normal acute myeloid leukemias and are associated with a more favorable outcome. We have devised a PCR-based assay for NPM1 exon 12 mutations using differential melting of an oligo probe labeled with a fluorescent dye. The nucleobase quenching (NBQ) phenomenon was used to detect probe hybridization, and an oligonucleotide containing locked nucleic acid (LNA) nucleotides was used as a PCR clamp to suppress amplification of the normal sequence and enhance the analytical sensitivity of the assay. After the NBQ assay, the specimens with a mutation were removed from the capillary and sequenced to identify the mutation. The use of the LNA clamp facilitates interpretation of the mutant sequence because of the lower intensity of the overlapping normal sequence. Analysis of a series of 70 patient specimens revealed 17 positive for an NPM1 mutation and 53 negatives. All of the NBQ results (positives and negatives) were confirmed with other methods. The analytical sensitivity of the NBQ assay is variable depending on the concentration of the PCR clamp and other parameters. Using a 100 nmol/L concentration of the LNA clamp, NPM1 mutations were detectable in a 10-fold excess of wild-type DNA. This assay may be valuable for screening disease specimens.


Engineering a deformation-free plastic spiral inertial microfluidic system for CHO cell clarification in biomanufacturing.
Inertial microfluidics has enabled many impactful high throughput applications. However, devices fabricated in soft elastomer (i.e., polydimethylsiloxane (PDMS)) suffer reliability issues due to significant deformation generated by the high pressure and flow rates in inertial microfluidics. In this paper, we demonstrated deformation-free and mass-producible plastic spiral inertial microfluidic devices for high-throughput cell separation applications. The design of deformable PDMS spiral devices was translated to their plastic version by compensating for the channel deformation in the PDMS devices, analyzed by numerical simulation and confocal imaging methods. The developed plastic spiral devices showed similar performance to their original PDMS devices for blood separation and Chinese hamster ovary (CHO) cell retention. Furthermore, using a multiplexed plastic spiral unit containing 100 spirals, we successfully demonstrated ultra-high-throughput cell clarification (at a processing rate of 1 L min-1) with a high cell-clarification efficiency of ∼99% (at the cell density changing from ∼2 to ∼10 × 106 cells mL-1). Benefitting from the continuous and clogging-free separation with an industry-level throughput, the cell clarification device could be a critical breakthrough for the production of therapeutic biologics such as antibodies or vaccines, impacting biomanufacturing in general.


Cognitive Decline in Post-treatment Lyme Disease Syndrome.
Patient-reported cognitive complaints are common in those with post-treatment Lyme disease syndrome (PTLDS). Objective evidence of cognitive impairment in this population is variable in part due to methodological variability in existing studies. In this study, we sought to use a systematic approach to characterizing PTLDS based on the most current consensus diagnosis. We further examined PTLDS-related cognitive decline, operationalized as a significant decline in cognitive test performance relative to premorbid cognitive ability. We enrolled a case series of 124 patients with confirmed PTLDS defined by Infectious Diseases Society of America-proposed case definition. Cognitive functioning was evaluated using standardized neuropsychological measures. The majority (92%) of participants endorsed some level of cognitive difficulty, yet 50% of the sample showed no statistically or clinically significant cognitive decline, 26% of the sample evidenced significant cognitive decline on measures of memory and variably on measures of processing speed, and 24% of the sample were excluded from analyses due to suboptimal test engagement. The current findings are consistent with the literature showing that the most robust neurocognitive deficit associated with PTLDS is in verbal memory and with variable decline in processing speed. Compared to population normative comparison standards, PTLDS-related cognitive decline remains mild. Thus, further research is needed to better understand factors related to the magnitude of subjective cognitive complaints as well as objective evidence of mild cognitive decline.


Can adipokines serum levels be used as biomarkers of hand osteoarthritis?
To evaluate serum levels of visfatin, resistin and adiponectin in patients with erosive (E) and non-erosive (NE) osteoarthritis (OA) of the hand (HOA) compared to normal controls (NC). 94 outpatients with E HOA and NE HOA and 21 NC were enrolled. The radiological assessment of both hands was performed according to the Kellgren-Lawrence and Kallman score. Patients were divided into two subsets (lone HOA or generalized OA) based on clinically OA involvement of knee and hip. Serum visfatin, resistin and adiponectin levels were determined by ELISA assay. Visfatin was significantly higher in E HOA patients in comparison to NC and NE HOA group. Resistin showed a significant increase in both E HOA and NE HOA groups versus NC, in particular in generalized OA. No significant differences among groups were found in adiponectin. The Kallman score was more severe in the two subsets of E HOA patients compared to NE HOA. This study showed increased levels of resistin in erosive and non-erosive HOA, and higher visfatin levels in E HOA in comparison to NE HOA. These data suggest the adipokines possible role in the pathogenesis of HOA and their potential usefulness as biomarkers of the disease.


Neuroprotective effects of inhaled lavender oil on scopolamine-induced dementia via anti-oxidative activities in rats.
Lavender is used in traditional medicines in Asia, Europe, ancient Greece and Rome, and was mentioned in the Bible and in ancient Jewish texts. Also, lavender is reported to be an effective medical plant in treating inflammation, depression, stress and headache. The present study was undertaken in order to investigate the antioxidant and antiapoptotic activities of the lavender essential oils from Lavandula angustifolia ssp. angustifolia Mill. and Lavandula hybrida Rev. using superoxide dismutase (SOD), glutathione peroxidase (GPX) and catalase (CAT) specific activities, total content of reduced glutathione (GSH), malondialdehyde (MDA) level (lipid peroxidation) and DNA fragmentation assays in male Wistar rats subjected to scopolamine-induced dementia rat model. In scopolamine-treated rats, lavender essential oils showed potent antioxidant and antiapoptotic activities. Subacute exposures (daily, for 7 continuous days) to lavender oils significantly increased antioxidant enzyme activities (SOD, GPX and CAT), total content of reduced GSH and reduced lipid peroxidation (MDA level) in rat temporal lobe homogenates, suggesting antioxidant potential. Also, DNA cleavage patterns were absent in the lavender groups, suggesting antiapoptotic activity. Taken together, our results suggest that antioxidant and antiapoptotic activities of the lavender essential oils are the major mechanisms for their potent neuroprotective effects against scopolamine-induced oxidative stress in the rat brain.


Cytokinin Response Factor 6 Represses Cytokinin-Associated Genes during Oxidative Stress.
Cytokinin is a phytohormone that is well known for its roles in numerous plant growth and developmental processes, yet it has also been linked to abiotic stress response in a less defined manner. Arabidopsis (Arabidopsis thaliana) Cytokinin Response Factor 6 (CRF6) is a cytokinin-responsive AP2/ERF-family transcription factor that, through the cytokinin signaling pathway, plays a key role in the inhibition of dark-induced senescence. CRF6 expression is also induced by oxidative stress, and here we show a novel function for CRF6 in relation to oxidative stress and identify downstream transcriptional targets of CRF6 that are repressed in response to oxidative stress. Analysis of transcriptomic changes in wild-type and crf6 mutant plants treated with H2O2 identified CRF6-dependent differentially expressed transcripts, many of which were repressed rather than induced. Moreover, many repressed genes also show decreased expression in 35S:CRF6 overexpressing plants. Together, these findings suggest that CRF6 functions largely as a transcriptional repressor. Interestingly, among the H2O2 repressed CRF6-dependent transcripts was a set of five genes associated with cytokinin processes: (signaling) ARR6, ARR9, ARR11, (biosynthesis) LOG7, and (transport) ABCG14. We have examined mutants of these cytokinin-associated target genes to reveal novel connections to oxidative stress. Further examination of CRF6-DNA interactions indicated that CRF6 may regulate its targets both directly and indirectly. Together, this shows that CRF6 functions during oxidative stress as a negative regulator to control this cytokinin-associated module of CRF6-dependent genes and establishes a novel connection between cytokinin and oxidative stress response.


What has changed in the evidence for early experience? Update of a BEME systematic review.
We previously reviewed evidence published from 1992 to 2001 concerning early experience for healthcare undergraduates (Dornan T, Littlewood S, Margolis S, Scherpbier A, Spencer J, Ypinazar V. 2006. How can experience in clinical and community settings contribute to early medical education? A BEME systematic review. Med Teach 28:3-18). This subsequent study reviews evidence published from 2002 to 2008. Identify changes in the evidence base; determine the value of re-reviewing; set a future research agenda. The same search strategy as in the original review was repeated. Newly identified publications were critically appraised against the same benchmarks of strength and educational importance. Twenty-four new empirical studies of early authentic experience in education of health professionals met our inclusion criteria, yielding 96 outcomes. Sixty five outcomes (from 22 studies) were both educationally important and based on strong evidence. A new significant theme was found: the use of early experience to help students understand and align themselves with patient and community perspectives on illness and healthcare. More publications were now from outside Europe and North America. In addition to supporting the findings of our original review, this update shows an expansion in research sources, and a shift in research content focus. There are still questions, however, about how early authentic experience leads to particular learning outcomes and what will make it most educationally effective.


Relationship between AtPase activity and conjugated polyamines in mitochondrial membrane from wheat seedling roots under osmotic stress.
The effects of osmotic stress on the ATPase activity, the contents of -SH group and conjugated polyamines in mitochondrial membrane from wheat seedling [Triticum aestivum L. cv. Yumai No. 18 (drought-tolerant) and cv. Yumai No. 9 (drought-sensitive)] roots were investigated. The results showed that ATPase activity and -SH group content decreased with polyethylene glycol(PEG) 6000(-0.55 MPa) treatment for 7 d, in concert with the decrease of the ratio of noncovalently conjugated spermidine (NCC-Spd)/noncovalently conjugated putrescine(NCC-Put) and increase of the covalently conjugated putrescine (CC-Put). Osmotic stress injury to Yangmai No.9 seedlings was alleviated greatly with 1 mmol/L exogenous spermidine(Spd), in concert with marked increases of the ratio of NCC-Spd/NCC-Put, -SH group contents and ATPase activity in mitochondrial membrane. Under osmotic stress, the concomitant treatment of Yumai No. 18 seedlings with methylglyoxyl bis(guanylhydrazone) (MGBG), an inhibitor of S-adenosyl methionine decarboxylase(SAMDC), and phenanthrolin (o-Phen), an inhibitor of transglutaminase(TGase), caused a significant decrease of the ratio of NCC-Spd/NCC-Put, CC-Put contents, respectively, in concert with the marked decreases of ATPase activity, -SH group content and its tolerance to osmotic stress. All the results above suggested that osmotic stress tolerance of wheat seedlings was associated with the ATPase activity, the contents of -SH group, NCC-Spd and CC-Put in mitochondrial membrane.


Neonatal Transport Ventilation: Simulation to Improve Knowledge and Skills.
Neonatal transport is a frequent activity in most tertiary and regional perinatal centers. Neonatal transport teams serve as mobile intensive care units and are equipped with specialized incubators that have built-in ventilators that can provide several levels of support. In our institution, we aim to educate all neonatal transport providers, including neonatal-perinatal fellows, neonatal intensive care unit-dedicated advanced practice providers, and neonatal intensive care unit-dedicated registered respiratory therapists, on transport ventilation management and troubleshooting, utilizing simulation to optimize patient care during transport. We developed scenarios based on the equipment used at our institution: an AirBorne Voyager transport incubator with a built-in Crossvent 2i+ infant ventilator, AirBorne TXP-2D high-frequency ventilator, and AeroNOx inhaled nitric oxide system (International Biomedical). Equipment and troubleshooting knowledge were assessed via knowledge tests prior to and at intervals after simulation scenario completion. We performed paired t tests to analyze change in test scores at each time point postsimulation compared to presimulation. Facilitated debriefing and a survey elicited feedback on learner confidence and comfort. Ten learners participated in the simulations and completed the knowledge assessments. At all postsimulation time points, mean knowledge scores showed statistically significant improvements compared to presimulation scores. Feedback from learners on confidence in their skills and comfort with the equipment was positive. Neonatal transport team ventilator knowledge and troubleshooting skills have improved after instituting this semiannual simulation training.


Concise Review: Developing Best-Practice Models for the Therapeutic Use of Extracellular Vesicles.
Growing interest in extracellular vesicles (EVs, including exosomes and microvesicles) as therapeutic entities, particularly in stem cell-related approaches, has underlined the need for standardization and coordination of development efforts. Members of the International Society for Extracellular Vesicles and the Society for Clinical Research and Translation of Extracellular Vesicles Singapore convened a Workshop on this topic to discuss the opportunities and challenges associated with development of EV-based therapeutics at the preclinical and clinical levels. This review outlines topic-specific action items that, if addressed, will enhance the development of best-practice models for EV therapies. Stem Cells Translational Medicine 2017;6:1730-1739.


Experimental determination of the radiation dose limit for cryocooled protein crystals.
Radiation damage to cryocooled protein crystals during x-ray structure determination has become an inherent part of macromolecular diffraction data collection at third-generation synchrotrons. Generally, radiation damage is an undesirable component of the experiment and can result in erroneous structural detail in the final model. The characterization of radiation damage thus has become an important area for structural biologists. The calculated dose limit of 2 x 10(7) Gy for the diffracting power of cryocooled protein crystals to drop by half has been experimentally evaluated at a third-generation synchrotron source. Successive data sets were collected from four holoferritin and three apoferritin crystals. The absorbed dose for each crystal was calculated by using the program raddose after measurement of the incident photon flux and determination of the elemental crystal composition by micro-particle-induced x-ray emission. Degradation in diffraction quality and specific structural changes induced by synchrotron radiation then could be compared directly with absorbed dose for different dose/dose rate regimes: a 10% lifetime decrease for a 10-fold dose rate increase was observed. Remarkable agreement both between different crystals of the same type and between apoferritin and holoferritin was observed for the dose required to reduce the diffracted intensity by half (D(1/2)). From these measurements, a dose limit of D(1/2) = 4.3 (+/-0.3) x10(7) Gy was obtained. However, by considering other data quality indicators, an intensity reduction to I(ln2) = ln2 x I(0), corresponding to an absorbed dose of 3.0 x 10(7) Gy, is recommended as an appropriate dose limit for typical macromolecular crystallography experiments.


Promoting patient safety: the rapid medical response team.
Adverse events are estimated to affect up to 17% of hospitalized patients and to cause up to 98,000 patient deaths per year in the United States. Unexpected codes in hospitalized patients are one of the most significant adverse events, carrying a risk of death that is reported to range from 50% to 80%. The Rapid Medical Response Team (RMRT) was an initiative designed to reduce adverse events, specifically failure to rescue, leading to nonintensive care unit (nonICU) codes. This initiative was funded, as part of the Transforming Care at the Bedside (TCAB) program, by a grant from the Robert Wood Johnson Foundation. To determine whether the RMRT had a significant impact on our nonICU code rate, we did a retrospective, noncohort comparison of 2004 (preRMRT) data with 2005 (postRMRT) data. Our main outcome measures were nonICU codes, mortality rate, and unplanned patient transfers to the intensive care unit (ICU). There was a decrease in the nonICU code rate per 1000 discharges from 1.90 in 2004 to 1.01 in 2005. Implementation of the RMRT correlates to a statistically significant decrease in the nonICU code rate (p = .018; relative risk, 0.53 [95% confidence interval, 0.31-0.91]). The nonICU mortality rate remained unchanged at 2.01%. The unplanned ICU transfer rate for 2005 was 47%. Implementation of RMRTs can decrease nonICU code rates and the rate of unplanned ICU transfers. RMRTs can empower staff, enhance expertise and communication skills, and support a culture of safety.


Identification of Potent In Vivo Autotaxin Inhibitors that Bind to Both Hydrophobic Pockets and Channels in the Catalytic Domain.
Autotaxin (ATX, also known as ENPP2) is a predominant lysophosphatidic acid (LPA)-producing enzyme in the body, and LPA regulates various physiological functions, such as angiogenesis and wound healing, as well as pathological functions, including proliferation, metastasis, and fibrosis, via specific LPA receptors. Therefore, the ATX-LPA axis is a promising therapeutic target for dozens of diseases, including cancers, pulmonary and liver fibroses, and neuropathic pain. Previous structural studies revealed that the catalytic domain of ATX has a hydrophobic pocket and a hydrophobic channel; these serve to recognize the substrate, lysophosphatidylcholine (LPC), and deliver generated LPA to LPA receptors on the plasma membrane. Most reported ATX inhibitors bind to either the hydrophobic pocket or the hydrophobic channel. Herein, we present a unique ATX inhibitor that binds mainly to the hydrophobic pocket and also partly to the hydrophobic channel, inhibiting ATX activity with high potency and selectivity in vitro and in vivo. Notably, our inhibitor can rescue the cardia bifida (two hearts) phenotype in ATX-overexpressing zebrafish embryos.


Chaplain Training in Evidence-Based Practices to Promote Mental Health and Improve Care for Suicidality in Veterans and Service Members.
Chaplains are key care providers in a comprehensive approach to suicide prevention, which is a priority area for the U.S. Department of Veterans Affairs (VA) and the Department of Defense (DoD). In a cohort of 87 VA and military chaplains who completed the Mental Health Integration for Chaplain Services (MHICS) training-an intensive, specialty education in evidence-based psychosocial and collaborative approaches to mental health care-we assessed chaplains' self-perceptions, intervention behaviors, and use of evidence-based practices, including Acceptance and Commitment Therapy (ACT), Problem-Solving Therapy (PST), and Motivational Interviewing (MI), in providing care for suicidality. Chaplains responded to a battery of items Pre- and Post-training and provided deidentified case examples describing their use of evidence-based practices in spiritual care for service members and veterans (SM/V) on various levels of a suicide prevention continuum. Post-training, chaplains reported increased abilities to provide care and mobilize collaborative resources. Over the course of MHICS, 87% of chaplains used one or more evidence-based practices with a SM/V at risk for suicide or acutely suicidal. Fifty-six percent of chaplains reported intervening with an acutely suicidal SM/V by using principles from ACT, 36% PST, and 48% MI. With persons at risk for suicide, 81% used principles from ACT, 66% PST, and 71% MI. Cases exemplified diverse evidence-based practice applications. Findings indicate chaplains trained in evidence-based practices report effective application in caring for SM/V who are suicidal, thus offering a valuable resource to meet needs in a priority area for VA and DoD.HIGHLIGHTSChaplains provide essential care for SM/V who are at risk for suicide or acutely suicidalTraining helps chaplains mobilize interdisciplinary and community resources in suicide careEvidence-based practices can effectively integrate within the scope of chaplaincy practice for suicide care.


Evaluating Markers of Immune Tolerance and Angiogenesis in Maternal Blood for an Association with Risk of Pregnancy Loss.
Pregnancy loss affects approximately 20% of couples. The lack of a clear cause complicates half of all miscarriages. Early evidence indicates the maternal immune system and angiogenesis regulation are both key players in implantation success or failure. Therefore, this prospective study recruited women in the first trimester with known viable intrauterine pregnancy and measured blood levels of immune tolerance proteins galectin-9 (Gal-9) and interleukin (IL)-4, and angiogenesis proteins (vascular endothelial growth factors (VEGF) A, C, and D) between 5 and 9 weeks gestation. Plasma concentrations were compared between groups defined based on (a) pregnancy outcome and (b) maternal history of miscarriage, respectively. In total, 56 women were recruited with 10 experiencing a miscarriage or pregnancy loss in the 2nd or 3rd trimester and 11 having a maternal history or miscarriage. VEGF-C was significantly lower among women with a miscarriage or pregnancy loss. Gal-9 and VEGF-A concentrations were decreased in women with a prior miscarriage. Identification of early changes in maternal immune and angiogenic factors during pregnancy may be a tool to improve patient counseling on pregnancy loss risk and future interventions to reduce miscarriage in a subset of women.