The 2020 annual report of DataDerm: The database of the American Academy of Dermatology.
The American Academy of Dermatology launched DataDerm in 2016 as the clinical data registry platform of the American Academy of Dermatology. DataDerm is approved by the Centers for Medicare & Medicaid Services as a Qualified Clinical Data Registry for the Merit-Based Incentive Payment System. The ultimate purpose of DataDerm is to provide dermatologists with a registry and database that will serve as a vehicle to advance the specialty in the domains of science, discovery, education, quality assessment, quality improvement, advocacy, and practice management. DataDerm is currently the largest clinical registry and database of patients receiving dermatologic care in the world. As of December 31, 2019, DataDerm contained data from 10,618,879 unique patients and 32,309,389 unique patient visits. Depending on the reporting period, 800 to 900 practices (representing 2400-2600 clinicians) actively participate in DataDerm by submitting data. This article provides the first of a planned series of annual updates of the status of DataDerm. The purpose of this article is to present the rationale for the creation, maintenance, history, and current status of DataDerm, as well as the future plans for DataDerm.


Photodynamic diagnosis of bladder cancer compared with white light cystoscopy: Systematic review and meta-analysis.
The aim of this study was to assess the test performance and clinical effectiveness of photodynamic diagnosis (PDD) compared with white light cystoscopy (WLC) in people suspected of new or recurrent bladder cancer. A systematic review was conducted of randomized controlled trials (RCTs), nonrandomized comparative studies, or diagnostic cross-sectional studies comparing PDD with WLC. Fifteen electronic databases and Web sites were searched (last searches April 2008). For clinical effectiveness, only RCTs were considered. Twenty-seven studies (2,949 participants) assessed test performance. PDD had higher sensitivity than WLC (92 percent, 95 percent confidence interval [CI], 80-100 percent versus 71 percent, 95 percent CI, 49-93 percent) but lower specificity (57 percent, 95 percent CI, 36-79 percent versus 72 percent, 95 percent CI, 47-96 percent). For detecting higher risk tumors, median range sensitivity of PDD (89 percent [6-100 percent]) was higher than WLC (56 percent [0-100 percent]) whereas for lower risk tumors it was broadly similar (92 percent [20-95 percent] versus 95 percent [8-100 percent]). Four RCTs (709 participants) using 5-aminolaevulinic acid (5-ALA) as the photosensitising agent reported clinical effectiveness. Using PDD at transurethral resection of bladder tumor (TURBT) resulted in fewer residual tumors at check cystoscopy (relative risk [RR], 0.37, 95 percent CI, 0.20-0.69) and longer recurrence-free survival (RR, 1.37, 95 percent CI, 1.18-1.59), compared with WLC. PDD detects more bladder tumors than WLC, including more high-risk tumors. Based on four RCTs reporting clinical effectiveness, 5-aminolaevulinic acid-mediated PDD at TURBT facilitates a more complete resection and prolongs recurrence-free survival.


The effect of silver nanoparticles and silver ions on zebrafish embryos (Danio rerio).
The aim of this study was to establish and evaluate the mortality rate, hatching rate and observe the presence of sublethal changes in zebrafish embryos after exposure to silver ions and nanoparticles. Tests were conducted on newly fertilized zebrafish embryos, according to the modified OECD guideline 236, using a semistatic method and 96 hour incubation time. Silver nitrate and two different silver nanoparticles, stabilized with 0.01% solution of maltose and gelatine in the first case, and stabilized with polyvinylpyrrolidone, in the latter, were tested. Significant differences in toxicity of tested substances were recorded. The value of 96hLC50 for silver nitrate was 58.44 μg/L. The value of 96hLC50, calculated for silver nanoparticles stabilized with 0.01% solution of maltose and gelatine, was nearly 100 times higher, 4.31 mg/L. The value 96hLC50 for silver nanoparticles stabilized with polyvinylpyrrolidone exceeded 100mg/L, occurrence of sublethal effects caused by silver nanoparticles stabilized with polyvinylpyrrolidone was insignificant in most of the exposition groups, but only in this substance caused decreased hatching rate. Properties of different silver nanoparticles play an important role in levels of their toxicity and predominant mechanisms of action. In general, silver nanoparticles are less toxic for Danio rerio embryos than silver ions.


Comparing ownership and use of bed nets at two sites with differential malaria transmission in western Kenya.
Challenges persist in ensuring access to and optimal use of long-lasting, insecticidal bed nets (LLINs). Factors associated with ownership and use may differ depending on the history of malaria and prevention control efforts in a specific region. Understanding how the cultural and social-environmental context of bed net use may differ between high- and low-risk regions is important when identifying solutions to improve uptake and appropriate use. Community forums and a household, cross-sectional survey were used to collect information on factors related to bed net ownership and use in western Kenya. Sites with disparate levels of transmission were selected, including an endemic lowland area, Miwani, and a highland epidemic-prone area, Kapkangani. Analysis of ownership was stratified by site. A combined site analysis was conducted to examine factors associated with use of all available bed nets. Logistic regression modelling was used to determine factors associated with ownership and use of owned bed nets. Access to bed nets as the leading barrier to their use was identified in community forums and cross-sectional surveys. While disuse of available bed nets was discussed in the forums, it was a relatively rare occurrence in both sites. Factors associated with ownership varied by site. Education, perceived risk of malaria and knowledge of individuals who had died of malaria were associated with higher bed net ownership in the highlands, while in the lowlands individuals reporting it was easy to get a bed net were more likely to own one. A combined site analysis indicated that not using an available bed net was associated with the attitudes that taking malaria drugs is easier than using a bed net and that use of a bed net will not prevent malaria. In addition, individuals with an unused bed net in the household were more likely to indicate that bed nets are difficult to use, that purchased bed nets are better than freely distributed ones, and that bed nets should only be used during the rainy season. Variations in factors associated with ownership should be acknowledged when constructing messaging and distribution campaigns. Despite reports of bed nets being used for other purposes, those in the home were rarely unused in these communities. Disuse seemed to be related to beliefs that can be addressed through education programmes. As mass distributions continue to take place, additional research is needed to determine if factors associated with LLIN ownership and use change with increasing availability of LLIN.


Novel DNA copy number losses in chromosome 12q12--q13 in adenoid cystic carcinoma.
In order to find common genetic abnormalities that may identify loci of genes involved in the development of adenoid cystic carcinoma (ACC), we investigated DNA copy number changes in 24 of these tumors by comparative genomic hybridization (CGH). Our results indicate that unlike many carcinomas, ACCs have relatively few changes in DNA copy number overall. Twenty tumors had DNA copy number changes, which were mostly restricted to a few chromosomal arms. A frequent novel finding was the loss of DNA copy number in chromosome 12q (eight tumors, 33%) with the minimal common overlapping region at 12q12--q13. Deletion in this region has not been reported to be frequent in other types of cancer analyzed by CGH. In addition, deletions in 6q23-qter and 13q21--q22 and gains of chromosome 19 were observed in 25% to 38% of ACCs. Deletion of 19q, previously reported in a small series of ACC, was not identified in the current group of carcinomas. The current CGH results for chromosomes 12 and 19 were confirmed by microsatellite allelotyping. These results indicate that DNA copy number losses in 12q may be important in the oncogenesis of ACC and suggest that the 12q12--q13 region may harbor a new tumor-suppressor gene.


Integration of Phytochrome and Cryptochrome Signals Determines Plant Growth during Competition for Light.
Plants in dense vegetation perceive their neighbors primarily through changes in light quality. Initially, the ratio between red (R) and far-red (FR) light decreases due to reflection of FR by plant tissue well before shading occurs. Perception of low R:FR by the phytochrome photoreceptors induces the shade avoidance response [1], of which accelerated elongation growth of leaf-bearing organs is an important feature. Low R:FR-induced phytochrome inactivation leads to the accumulation and activation of the transcription factors PHYTOCHROME-INTERACTING FACTORs (PIFs) 4, 5, and 7 and subsequent expression of their growth-mediating targets [2, 3]. When true shading occurs, transmitted light is especially depleted in red and blue (B) wavelengths, due to absorption by chlorophyll [4]. Although the reduction of blue wavelengths alone does not occur in nature, long-term exposure to low B light induces a shade avoidance-like response that is dependent on the cryptochrome photoreceptors and the transcription factors PIF4 and PIF5 [5-7]. We show in Arabidopsis thaliana that low B in combination with low R:FR enhances petiole elongation similar to vegetation shade, providing functional context for a low B response in plant competition. Low B potentiates the low R:FR response through PIF4, PIF5, and PIF7, and it involves increased PIF5 abundance and transcriptional changes. Low B attenuates a low R:FR-induced negative feedback loop through reduced gene expression of negative regulators and reduced HFR1 levels. The enhanced response to combined phytochrome and cryptochrome inactivation shows how multiple light cues can be integrated to fine-tune the plant's response to a changing environment.


Cancer chemopreventive activity and metabolism of isoliquiritigenin, a compound found in licorice.
Isoliquiritigenin (2',4',4-trihydroxychalcone; ILG), a chalcone found in licorice root and many other plants, has shown potential chemopreventive activity through induction of phase II enzymes such as quinone reductase-1 in murine hepatoma cells. In this study, the in vivo metabolism of ILG was investigated in rats. In addition, ILG glucuronides and ILG-glutathione adducts were observed in human hepatocytes and in livers from rats treated with ILG. ILG glucuronides were detected in both plasma and rat liver tissues. In addition, in a full-term cancer chemoprevention study conducted with 7,12-dimethylbenz(a)anthracene-treated female Sprague-Dawley rats, dietary administration of ILG slightly increased tumor latency but had a negative effect on the incidence of mammary tumors starting at approximately 65 days after 7,12-dimethylbenz(a)anthracene administration. Further, no significant induction of phase II enzymes was found in mammary glands, which is consistent with the low level of ILG observed in these tissues. However, ILG significantly induced quinone reductase-1 activity in the colon, and glutathione as well as glutathione S-transferase in the liver. Analysis of mRNA expression in tissues of rats treated with ILG supported these findings. These results suggest that ILG should be tested for chemopreventive efficacy in nonmammary models of cancer.


Countertransference in conflict: one client or two?
The concept of countertransference (CT) reaction has undergone dramatic changes in definition since its inception at the turn of the century. No longer viewed as a hindrance to effective therapeutic interventions, it has become central to building the therapeutic alliance. However, CT can interfere with the therapeutic task, and this is especially true in forensic settings in which one must help particularly difficult clients. In these cases, the CT must split into two parts in order for the therapist to be clinically effective. The therapist reacts to the individual as both an offender who has violated a societal law and as a client who needs help, separating the client from the behavior. Although not recognized explicitly in the forensic literature, the effects of the dual CT underlie investigations of therapist-offender relationships. This article reviews the concept of CT with specific reference to forensic settings and develops the concept of dual CT.


In-Frame Deletion and Missense Mutations of the C-Terminal Helicase Domain of SMARCA2 in Three Patients with Nicolaides-Baraitser Syndrome.
Using high-resolution molecular karyotyping with SNP arrays to identify candidate genes for etiologically unexplained intellectual disability, we identified a 32-kb de novo in-frame deletion of the C-terminal helicase domain of the SMARCA2 gene in a patient with severe intellectual disability, epilepsy, sparse hair, prominent joints, and distinct facial anomalies. Sequencing of the gene in patients with a similar phenotype revealed de novo missense mutations in this domain in 2 further patients, pointing to a crucial role of the SMARCA2 C-terminal helicase domain. The clinical features observed in all 3 patients are typical of Nicolaides-Baraitser syndrome, an only rarely reported syndrome with mainly moderate to severe intellectual disability. Notably, one of our patients with a p.Gly1132Asp mutation showed typical morphological features but an exceptional good development with borderline overall IQ and learning difficulties, thus expanding the phenotypic spectrum of Nicolaides-Baraitser syndrome.


A systematic review and meta-analysis of qigong for the fibromyalgia syndrome.
Objectives. The fibromyalgia syndrome (FMS) is a chronic condition with only few evidence-based complementary and alternative therapies available. This paper presents a systematic review and meta-analysis of the effectiveness of Qigong for fibromyalgia syndrome. Methods. The PubMed/MEDLINE, Cochrane Library, Embase, PsycINFO, and Cambase databases were screened in December 2012 to identify randomized controlled trials comparing Qigong to control interventions. Major outcome measures were pain and quality of life; and secondary outcomes included sleep quality, fatigue, depression, and safety. Standardized mean differences (SMD) and 95% confidence intervals were calculated. Results. Seven trials were located with a total of 395 FMS patients. Analyses revealed low quality evidence for short-term improvement of pain, quality of life, and sleep quality and very low quality evidence for improvement of fatigue after Qigong for FMS, when compared to usual care. No evidence was found for superiority of Qigong compared to active treatments. No serious adverse events were reported. Discussion. This systematic review found that Qigong may be a useful approach for FMS patients. According to the quality of evidence, only a weak recommendation for Qigong can be made at this point. Further high quality RCTs are required for the conclusive judgment of its long-term effects.


Incidence of Pituitary Apoplexy and Its Risk Factors in Chinese People: A Database Study of Patients with Pituitary Adenoma.
There are few studies of the incidence and clinical characteristics of pituitary apoplexy (PA) in pituitary adenoma patients, and the findings have been inconsistent. The aim of the study was to retrospectively assess the incidence, clinical presentation, surgical management and postoperative complications of PA in pituitary adenoma patients. A database was specifically designed to collect clinical, therapeutic, prognostic and histological information about pituitary adenoma patients. Using multivariate logistic regression, odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to identify associated factors. A total of 2021 pituitary adenoma patients were recruited. 97 (4.8%) patients had PA. The incidence of PA was 10.11% in patients with pituitary macroadenoma, and 0.36% in patients with microadenoma. Variables for the logistic regression model independently associated with PA were sex (male vs. female, OR = 2.54, 95% CI: 1.59~4.07), tumor type (negative staining vs. positive staining, OR = 2.04, 95% CI: 1.29~3.23), and tumor size (macroadenoma vs. microadenoma, OR = 26.46, 95% CI = 9.66~72.46). Headache, visual deterioration, and vomiting were the most common symptoms in patients with pituitary adenoma. Patients with and without PA had similar frequency of visual deterioration, head trauma, acromegalic appearance, galactorrhoea, cold intolerance and Cushingoid appearance, but headache, vomiting, ptosis, diplopia, fever and blindness were significantly more common in patients with PA. Pearson Chi-Square tests revealed a significant difference in surgical approach between patients with and without PA (95.88% vs. 85.57%, P = 0.01). Our findings suggest that PA is not a rare event. Male sex, non-functioning tumor, and macroadenoma are associated with an increased risk of PA. Compared with pituitary adenoma patients without PA, patients with PA have more severe symptoms.


Cloning of bcl-6, the locus involved in chromosome translocations affecting band 3q27 in B-cell lymphoma.
Chromosomal translocations involving band 3q27 and various chromosomal sites, including the sites of the immunoglobulin (Ig) loci (14q32, 2p12, 22q11), represent recurrent aberrations in non-Hodgkin's lymphoma (NHL). In order to identify the putative protooncogene involved in these translocations, we have cloned the breakpoints from two B-cell NHL cases carrying t(3;14)(q27;q32) translocations by screening genomic DNA libraries constructed from NHL biopsy samples with immunoglobulin probes. Several recombinant phages have been obtained from each case and shown to contain sequences from both 14q32 and 3q27 by fluorescence in situ hybridization mapping on metaphase chromosomes. In both cases, the translocation breakpoints were found within the switch region of the Ig heavy-chain locus on 14q32 and within the same 3-kilobase region on 3q27. When used in Southern blot hybridization, a probe from the 3q27 region detected rearrangements in an additional five NHL cases carrying 3q27 translocations with 14q32 or other genomic sites. The same probe detected a predominant 2.4-kilobase mRNA species in several lymphoid cell lines analyzed by Northern blot hybridization. These data suggest that chromosomal breakpoints in 3q27 cluster in the proximity of a transcribed gene which represents a candidate protooncogene (bcl-6) involved in B-cell NHL pathogenesis.


Flat spectral response silicon arrayed waveguide gratings via ion implantation.
A flat spectral response has long been a requirement in photonic networking. In order to find a low cost alternative compared to some other technologies, a novel method is demonstrated to achieve such a response in silicon-on-insulator arrayed waveguide gratings (AWG) through free carrier absorption, implemented by ion implantation of dopant species. The AWG is designed using 1.5mum Si-overlayer on an SOI wafer utilising rib waveguides with a width of 1.1mum and an etch-depth of 0.88mum to facilitate the single-mode, birefringence-free operation. It is also essential to achieve a uniform dopant concentration throughout the guiding region to avoid any phase errors resulting from the free carriers. This can be achieved using multiple ion implantation steps. Both n and p type dopants are investigated and results showed significant reduction of doping length is achieved by using n-type dopant as compared to a p-type dopants. The broadened passband is measured to be 0.5nm, a 5 times broadening from the Gaussian peak.


Calcium release channel RyR2 regulates insulin release and glucose homeostasis.
The type 2 ryanodine receptor (RyR2) is a Ca2+ release channel on the endoplasmic reticulum (ER) of several types of cells, including cardiomyocytes and pancreatic β cells. In cardiomyocytes, RyR2-dependent Ca2+ release is critical for excitation-contraction coupling; however, a functional role for RyR2 in β cell insulin secretion and diabetes mellitus remains controversial. Here, we took advantage of rare RyR2 mutations that were identified in patients with a genetic form of exercise-induced sudden death (catecholaminergic polymorphic ventricular tachycardia [CPVT]). As these mutations result in a "leaky" RyR2 channel, we exploited them to assess RyR2 channel function in β cell dynamics. We discovered that CPVT patients with mutant leaky RyR2 present with glucose intolerance, which was heretofore unappreciated. In mice, transgenic expression of CPVT-associated RyR2 resulted in impaired glucose homeostasis, and an in-depth evaluation of pancreatic islets and β cells from these animals revealed intracellular Ca2+ leak via oxidized and nitrosylated RyR2 channels, activated ER stress response, mitochondrial dysfunction, and decreased fuel-stimulated insulin release. Additionally, we verified the effects of the pharmacological inhibition of intracellular Ca2+ leak in CPVT-associated RyR2-expressing mice, in human islets from diabetic patients, and in an established murine model of type 2 diabetes mellitus. Taken together, our data indicate that RyR2 channels play a crucial role in the regulation of insulin secretion and glucose homeostasis.


Correlation of Acoustic Radiation Force Impulse Imaging with Chronicity Markers in Native Renal Biopsy.
Introduction. Acoustic Radiation Force Impulse (ARFI) is an ultrasound parameter which has shown promise in assessing liver stiffness, but there are limited data on the correlation of ARFI with chronicity markers in renal biopsies. Objectives. Determine ARFI values in ultrasound and correlate with chronicity markers in renal biopsy. Determine whether ARFI can be used as a non-invasive chronicity predictor compared to renal length, Resistive Index (RI), and cortical thickness. Patients and Methods. Two hundred and fifty patients were enrolled in the study. The ultrasound variables ARFI, renal length, RI, and cortical thickness values were assessed by the radiologist prior to renal biopsy. The biopsy slides were graded as per the Mayo Clinic consensus report scoring system by an experienced pathologist. Results. Among 250 study participants, 167 were males and 83 were females. IgA nephropathy was the most common pathology (n=47;19%), followed by diabetic nephropathy (n=42;17%), membranous nephropathy (n=35;14%), FSGS (n=27;11%), and MCD (n=19; 8%). The mean eGFR was 55.9 ± 42.12 ml/min/1.73 m2. The average renal length was 10.086 ± 1.01 cm. The average cortical thickness was 0.707 ± 0.134 cm. Resistive index was 0.68 ± 0.09. Acoustic radiation force impulse had weak negative correlation (r=-0.286; p=0.0001) with total pathological score and weak positive correlation with eGFR (r=0.279; p=0.0001). RI was a better indicator for histologically evaluated chronicity with positive correlation coefficient (r=0.416; p=0.0005) compared to renal length, cortical thickness, and ARFI. Conclusion. ARFI didn't corelate with the pathological score in renal biopsies. RI had better predictive value for chronicity in native renal biopsies.


Vascular endothelial growth factor stimulates protein kinase C-dependent phospholipase D activity in endothelial cells.
Many tumors produce vascular endothelial growth factor (VEGF), a paracrine factor acting selectively on endothelial cells. VEGF has many effects on cultured endothelial cells and mediates angiogenesis and enhanced vascular permeability in vivo. The endothelial signal transduction pathways of VEGF represent novel targets for cancer therapy because they are readily accessible to systemically administered drugs. We have examined VEGF-stimulated signals generated in HUVEC to identify potential targets for therapeutic intervention. The transphosphatidylation reaction has been used to monitor phospholipase D (PLD) activity; total inositol phosphates have been measured after prelabeling of cells with [3H]myoinositol; and intracellular free calcium has been measured using Fura-2 fluorescence. After HUVEC-stimulation with VEGF, there is an early influx of calcium (maximal by 100 seconds) followed by activation of PLD (half maximal by 100 seconds, EC50 70 pm). The PLD activity was inhibited by reducing extracellular calcium (150 nM, 50% inhibition), exposure to 12-O-tetradecanoylphorbol 13 acetate (200 nM, 24 hours, 100% inhibition), Roche 31,8220 (10 microM, 15 minutes, 72% inhibition), or genestein (100 microM, 30 minutes, 56% inhibition), which suggests a dependence on both protein kinase C and tyrosine phosphorylation. Activation of phospholipase C-catalyzed hydrolysis of phosphatidylinositol-4,5-bisphosphate was inferred from the production of inositol phosphates, although this response was slower (half maximal by 3 minutes). The phospholipase C activity was also dependent on influx of calcium and was partially inhibited by low (150 nM) extracellular calcium. PLD may be involved in mediating a number of endothelial responses to tumor-secreted VEGF, notably cytoskeleton-dependent effects such as the cell migration involved in angiogenesis. This signal transduction pathway could represent an accessible and vulnerable target for cancer therapeutic intervention and has the novelty of being located within normal cells rather than tumor cells.


IL-12-producing monocytes and HLA-E control HCMV-driven NKG2C+ NK cell expansion.
Human cytomegalovirus (HCMV) infection is the most common cause of congenital viral infections and a major source of morbidity and mortality after organ transplantation. NK cells are pivotal effector cells in the innate defense against CMV. Recently, hallmarks of adaptive responses, such as memory-like features, have been recognized in NK cells. HCMV infection elicits the expansion of an NK cell subset carrying an activating receptor heterodimer, comprising CD94 and NKG2C (CD94/NKG2C), a response that resembles the clonal expansion of adaptive immune cells. Here, we determined that expansion of this NKG2C(+) subset and general NK cell recovery rely on signals derived from CD14(+) monocytes. In a coculture system, a subset of CD14(+) cells with inflammatory monocyte features produced IL-12 in response to HCMV-infected fibroblasts, and neutralization of IL-12 in this model substantially reduced CD25 upregulation and NKG2C(+) subset expansion. Finally, blockade of CD94/NKG2C on NK cells or silencing of the cognate ligand HLA-E in infected fibroblasts greatly impaired expansion of NKG2C(+) NK cells. Together, our results reveal that IL-12, CD14(+) cells, and the CD94/NKG2C/HLA-E axis are critical for the expansion of NKG2C(+) NK cells in response to HCMV infection. Moreover, strategies targeting the NKG2C(+) NK cell subset have the potential to be exploited in NK cell-based intervention strategies against viral infections and cancer.


How the economic recession has changed the likelihood of reporting poor self-rated health in Spain.
Between 2006 and 2011 self-rated health (SRH) (the subjective report of an individual's health status) actually improved in Spain despite its being in the grips of a serious economic recession. This study examines whether the likelihood of reporting poor health has changed because of the global financial crisis. It also attempts to estimate the differences between SRH and other self-perceived measures of health among groups before and during the current economic crisis in Spain. Cross-sectional population-based surveys were conducted in Spain (ENSE 2006 and ENSE 2011) and in Catalonia (ESCA 2006 and ESCA 2011) in 2006 and again in 2011. In this research work we have used random effects logistic models (dependent variable SRH 1 Poor, 0 Good) and exact matching and propensity score-matching. The results of the ENSE explanatory variables are the same in both 2006 and 2011. In other words, all diseases negatively affect SRH, whereas alcohol habits positively affect SRH and obesity is the only disease unrelated to SRH. ESCA explanatory variables' results show that in 2006 all diseases are significant and have large odds ratio (OR) and consequently those individuals suffering from any of these diseases are more likely to report poor health. In 2011 the same pattern follows with the exception of allergies, obesity, high cholesterol and hypertension, albeit they are not statistically significant. Drinking habits had a positive effect on SRH in 2006 and 2011, whereas smoking is considered as unrelated to SRH. The likelihood of reporting poor health in 2006 is added as a variable in with the logistic regression of 2011 and is not, in either the ENSE data or the ESCA data, significant. Furthermore, neither is it significant when controlling by age, gender, employment status or education. The results of our analysis show that the financial crisis did not alter the likelihood of reporting poor health in 2011. Therefore, there are no differences between our perceived health in either 2006 or in 2011.


Abnormal regulation of venous alanine after glucose ingestion in myotonic dystrophy.
The concentration of amino acids in whole blood was measured before and during standard 5 h oral glucose tolerance testing in six male patients with myotonic dystrophy and five normal males. The plasma levels of insulin and glucose were also determined. From 90 to 240 min after glucose ingestion there was a striking decline in venous alanine concentration in the patients with myotonic dystrophy in contrast to a slight rise in alanine in the normal group. The patients displayed normal glucose tolerance, and there was a sustained fall in the venous concentration of the insulin-sensitive amino acids comparable with that seen in the normal controls. However, the patients showed a threefold increase of plasma insulin after glucose. These data indicate an abnormal regulation of alanine in myotonic dystrophy which may be the result of an alteration in muscle synthesis of this amino acid. This defect in alanine synthesis may be due to a decreased availability of intracellular pyruvate caused by the insulin resistance that exists in these patients.


"Dense diffusion" in colloidal glasses: short-ranged long-time self-diffusion as a mechanistic model for relaxation dynamics.
Despite decades of exploration of the colloidal glass transition, mechanistic explanation of glassy relaxation processes has remained murky. State-of-the-art theoretical models of the colloidal glass transition such as random first order transition theory, active barrier hopping theory, and non-equilibrium self-consistent generalized Langevin theory assert that relaxation reported at volume fractions above the ideal mode coupling theory prediction φg,MCT requires some sort of activated process, and that cooperative motion plays a central role. However, discrepancies between predicted and measured values of φg and ambiguity in the role of cooperative dynamics persist. Underlying both issues is the challenge of conducting deep concentration quenches without flow and the difficulty in accessing particle-scale dynamics. These two challenges have led to widespread use of fitting methods to identify divergence, but most a priori assume divergent behavior; and without access to detailed particle dynamics, it is challenging to produce evidence of collective dynamics. We address these limitations by conducting dynamic simulations accompanied by experiments to quench a colloidal liquid into the putative glass by triggering an increase in particle size, and thus volume fraction, at constant particle number density. Quenches are performed from the liquid to final volume fractions 0.56 ≤ φ ≤ 0.63. The glass is allowed to age for long times, and relaxation dynamics are monitored throughout the simulation. Overall, correlated motion acts to release dynamics from the glassy plateau - but only over length scales much smaller than a particle size - allowing self-diffusion to re-emerge; self-diffusion then relaxes the glass into an intransient diffusive state, which persists for φ < 0.60. We observe similar relaxation dynamics up to φ = 0.63 before achieving the intransient state. We find that this long-time self-diffusion is short-ranged: analysis of mean-square displacement reveals a glassy cage size a fraction of a particle size that shrinks with quench depth, i.e. increasing volume fraction. Thus the equivalence between cage size and particle size found in the liquid breaks down in the glass, which we confirm by examining the self-intermediate scattering function over a range of wave numbers. The colloidal glass transition can hence be viewed mechanistically as a shift in the long-time self-diffusion from long-ranged to short-ranged exploration of configurations. This shift takes place without diverging dynamics: there is a smooth transition as particle mobility decreases dramatically with concomitant emergence of a dense local configuration space that permits sampling of many configurations via local particle motion.


Exciton optoelectronic transistor.
We demonstrate experimental proof of principle for an optoelectronic transistor based on the modulation of exciton flux via gate voltage. The exciton optoelectronic transistor (EXOT) implements electronic operation on photons by using excitons as intermediate media; the intensity of light emitted at the optical output is proportional to the intensity of light at the optical input and is controlled electronically by the gate. We demonstrate a contrast ratio of 30 between an on state and an off state of the EXOT and its operation at speeds greater than 1 GHz. Our studies also demonstrate high-speed control of both the flux and the potential energy of excitons on a time scale much shorter than the exciton lifetime.


Intravenous immunoglobulin for ANCA-associated systemic vasculitis with persistent disease activity.
Intravenous immunoglobulin (IVIg) is a potential alternative treatment for anti-neutrophil cytoplasm antibody (ANCA)-associated systemic vasculitis (AASV) with less toxicity than conventional immunosuppressive agents. This randomized, placebo-controlled trial aimed to investigate the efficacy of a single course of IVIg (total dose 2 g/kg) in previously-treated AASV with persistent disease activity in whom there was an intention to escalate therapy. Vasculitic activity was monitored by the Birmingham vasculitis activity score (BVAS), C-reactive protein (CRP) and ANCA levels. Treatment response was defined as a reduction in BVAS of more than 50% after 3 months, and there was an intention to keep doses of concurrent immunosuppressive drugs unchanged during this period; follow-up continued to 12 months. Seventeen patients were randomized to receive IVIg and 17 to receive placebo. Treatment responses were found in 14/17 and 6/17 of the IVIg and placebo groups, respectively (p=0.015, OR 8.56, 95%CI 1.74-42.2). Following infusion of trial medication, greater falls in CRP were seen at 2 weeks (p=0.02) and 1 month (p=0.04) in the IVIg group. No differences were observed between ANCA levels or cumulative exposure to immunosuppressive drugs, and after 3 months there were no differences in CRP levels or disease activity between the IVIg and placebo groups. Seventeen adverse effects occurred after IVIg and six after placebo: they were mostly mild, although reversible rises in serum creatinine occurred in four from the IVIg group. A single course of IVIg reduced disease activity in persistent AASV, but this effect was not maintained beyond 3 months; mild, reversible side-effects following IVIg were frequent. IVIg is an alternative treatment for AASV with persistent disease activity after standard therapy.


The Use of Venovenous Extracorporeal Membrane Oxygenation in COVID-19 Infection: One Region's Comprehensive Experience.
Severe acute respiratory distress syndrome (ARDS) unresponsive to conventional intensive care unit (ICU) management is an accepted indication for venovenous extracorporeal membrane oxygenation (V-V ECMO) support. The frequency with which patients with coronavirus disease 2019 (COVID-19) pneumonia are selected for V-V ECMO has not been described. This was a cohort study including all patients placed on either V-V ECMO or venoarteriovenous ECMO at the four adult ECMO Centers of Excellence. Primary outcomes evaluated were survival to decannulation from the ECMO circuit, survival to discharge, and 60-day survival. Secondary outcomes were hospital length of stay (LOS), ICU LOS, length of ECMO cannulation, and length of intubation. During the study period, which corresponded to the first surge in COVID-19 hospitalizations in Minnesota, 35 patients with ARDS were selected for V-V ECMO support out of 1,849 adult ICU patients with COVID-19 infection in the state (1.9% incidence; 95% CI, 1.3-2.6%). This represents 46 (95% CI, 34-61) expected V-V ECMO patients per 100,000 confirmed positive cases of COVID-19. Twenty-six of the 35 patients (74.3%) supported with V-V ECMO survived to 60-day post-ECMO decannulation. Recent studies have demonstrated ongoing success rescuing patients with severe ARDS in COVID-19 infection. Our data add to the support of ECMO and the consideration for encouraging cooperation among regional ECMO centers to ensure access to this highest level of care. Finally, by evaluating all the patients of a single region, we estimate overall need for this resource intensive intervention based on the overall number of COVID-19 cases and ICU admissions.


Effectiveness of culturally tailoring smoking cessation interventions for reducing or quitting combustible tobacco: A systematic review and meta-analyses.
Standard approaches to smoking cessation may not be as effective for certain populations, and tailoring on cultural factors could improve their effectiveness. This systematic review measured the effectiveness of culturally tailoring smoking cessation interventions on quitting or reducing smoking combustible tobacco. We searched MEDLINE, PsychInfo, Embase and Cochrane Central Register from inception to 21 June 2023 for randomized controlled trials (RCTs) of community-based, primary care or web-based interventions for smoking cessation in adults who smoked tobacco, with measurement of smoking abstinence or reduction at least 3 months following baseline. We examined comparisons between either an intensity-matched culturally tailored intervention and a non-tailored intervention or a standard non-tailored intervention and the same intervention plus a culturally tailored adjunct. We sub-grouped studies according to the level of tailoring and performed subgroup analyses where appropriate. We assessed risk of bias and certainty of evidence. We identified 43 studies, 33 of which were meta-analyzed (n = 12 346 participants). We found moderate certainty evidence, limited by heterogeneity, that intensity-matched culturally tailored cessation interventions increased quit success when compared with non-tailored interventions at 3-month follow-up or longer (n = 5602, risk ratio [RR] = 1.29 95% confidence interval [CI] 1.10, 1.51, I2 = 47%, 14 studies). We found a positive effect of adding a culturally tailored component to a standard intervention compared with the standard intervention alone (n = 6674, RR = 1.47, 95% CI 1.10, 1.95, I2 = 74%, 18 studies), but our certainty in this effect was low due to imprecision and substantial statistical heterogeneity. Culturally tailored smoking cessation interventions may help more people to quit smoking than a non-tailored intervention. Adapting or adding cultural components to smoking cessation interventions originally developed for majority populations could improve cessation rates in populations who do not fully identify with majority cultural norms.


Nano-mechanical tuning and imaging of a photonic crystal micro-cavity resonance.
We show that nano-mechanical interaction using atomic force microscopy (AFM) can be used to map out mode-patterns of an optical micro-resonator with high spatial accuracy. Furthermore we demonstrate how the Q-factor and center wavelength of such resonances can be sensitively modified by both horizontal and vertical displacement of an AFM tip consisting of either Si(3)N(4) or Si material. With a silicon tip we are able to tune the resonance wavelength by 2.3 nm, and to set Q between values of 615 and zero, by expedient positioning of the AFM tip. We find full on/off switching for less than 100 nm vertical, and for 500 nm lateral displacement at the strongest resonance antinode locations.


Supervised Segmentation of Un-Annotated Retinal Fundus Images by Synthesis.
We focus on the practical challenge of segmenting new retinal fundus images that are dissimilar to existing well-annotated data sets. It is addressed in this paper by a supervised learning pipeline, with its core being the construction of a synthetic fundus image data set using the proposed R-sGAN technique. The resulting synthetic images are realistic-looking in terms of the query images while maintaining the annotated vessel structures from the existing data set. This helps to bridge the mismatch between the query images and the existing well-annotated data set. As a consequence, any known supervised fundus segmentation technique can be directly utilized on the query images, after training on this synthetic data set. Extensive experiments on different fundus image data sets demonstrate the competitiveness of the proposed approach in dealing with a diverse range of mismatch settings.


Identifying metabolic syndrome in a clinical cohort: Implications for prevention of chronic disease.
In the clinical setting, calculating cardiovascular disease (CVD) risk is commonplace but the utility of the harmonised equation for metabolic syndrome (MetS) (Alberti et al., 2009) is less well established. The aims of this study were to apply this equation to an overweight clinical cohort to identify risk factors for being metabolically unhealthy and explore associations with chronic disease. Baseline data were analysed from a lifestyle intervention trial of Illawarra residents recruited in 2014/2015. Participants were aged 25-54 years with a BMI 25-40 kg/m2. Data included MetS, CVD risk, insulin sensitivity, weight, body fat, diet, peripheral artery disease (PAD), physical activity, socio-economic position and psychological profile. Backward stepwise regression tested the association of covariates with MetS status and linear or logistic regression tested associations between MetS and risk of CVD, coronary heart disease, PAD and insulin resistance. 374 participants were included in the analysis with 127 (34.0%) categorised with MetS. Covariates significantly and positively associated with MetS were higher BMI (odds 1.26, p < 0.01) and older age (odds 1.08, p < 0.01). MetS participants (n = 351) had a 4.50% increase in CVD risk and were 8.1 and 12.7 times (respectively) more likely to be at risk of CHD and insulin resistance, compared to participants without MetS. The utility of the harmonised equation in the clinical setting was confirmed in this overweight clinical cohort. Those classified as having MetS were more likely to be older, overweight/obese individuals and they had a substantially higher risk of developing CVD and insulin resistance than those without MetS.


Effect of Anti-CD4 Antibody UB-421 on HIV-1 Rebound after Treatment Interruption.
Administration of a single broadly neutralizing human immunodeficiency virus (HIV)-specific antibody to HIV-infected persons leads to the development of antibody-resistant virus in the absence of antiretroviral therapy (ART). It is possible that monotherapy with UB-421, an antibody that blocks the virus-binding site on human CD4+ T cells, could induce sustained virologic suppression without induction of resistance in HIV-infected persons after analytic treatment interruption. We conducted a nonrandomized, open-label, phase 2 clinical study evaluating the safety, pharmacokinetics, and antiviral activity of UB-421 monotherapy in HIV-infected persons undergoing analytic treatment interruption. All the participants had undetectable plasma viremia (<20 copies of HIV RNA per milliliter) at the screening visit. After discontinuation of ART, participants received eight intravenous infusions of UB-421, at a dose of either 10 mg per kilogram of body weight every week (Cohort 1) or 25 mg per kilogram every 2 weeks (Cohort 2). The primary outcome was the time to viral rebound (≥400 copies per milliliter). A total of 29 participants were enrolled, 14 in Cohort 1 and 15 in Cohort 2. Administration of UB-421 maintained virologic suppression (<20 copies per milliliter) in all the participants (94.5% of measurements at study visits 2 through 9) during analytic treatment interruption, with intermittent viral blips (range, 21 to 142 copies per milliliter) observed in 8 participants (28%). No study participants had plasma viral rebound to more than 400 copies per milliliter. CD4+ T-cell counts remained stable throughout the duration of the study. Rash, mostly of grade 1, was a common and transient adverse event; one participant discontinued the study drug owing to a rash. A decrease in the population of CD4+ regulatory T cells was observed during UB-421 monotherapy. UB-421 maintained virologic suppression (during the 8 to 16 weeks of study) in participants in the absence of ART. One participant discontinued therapy owing to a rash. (Funded by United Biomedical and others; ClinicalTrials.gov number, NCT02369146.).


Sequential contribution of L- and P-selectin to leukocyte rolling in vivo.
Leukocyte recruitment into inflammatory sites is initiated by a reversible transient adhesive contact with the endothelium called leukocyte rolling, which is thought to be mediated by the selectin family of adhesion molecules. Selectin-mediated rolling precedes inflammatory cell emigration, which is significantly impaired in both P- and L-selectin gene-deficient mice. We report here that approximately 13% of all leukocytes passing venules of the cremaster muscle of wild-type mice roll along the endothelium at < 20 min after surgical dissection. Rolling leukocyte flux fraction reaches a maximum of 28% at 40-60 min and returns to 13% at 80-120 min. In P-selectin-deficient mice, rolling is absent initially and reaches 5% at 80-120 min. Rolling flux fraction in L-selectin-deficient mice is similar to wild type initially and declines to 5% at 80-120 min. In both wild-type and L-selectin-deficient mice, initial leukocyte rolling (0-60 min) is completely blocked by the P-selectin monoclonal antibody (mAb) RB40.34, but unaffected by L-selectin mAb MEL-14. Conversely, rolling at later time points (60-120 min) is inhibited by mAb MEL-14 but not by mAb RB40.34. After treatment with tumor necrosis factor (TNF)-alpha for 2 h, approximately 24% of all passing leukocytes roll in cremaster venules of wild-type and P-selectin gene-deficient mice. Rolling in TNF-alpha-treated mice is unaffected by P-selectin mAb or E-selectin mAb 10E9.6. By contrast, rolling in TNF-alpha-treated P-selectin-deficient mice is completely blocked by L-selectin mAb. These data show that P-selectin is important during the initial induction of leukocyte rolling after tissue trauma. At later time points and in TNF-alpha-treated preparations, rolling is largely L-selectin dependent. Under the conditions tested, we are unable to find evidence for involvement of E-selectin in leukocyte rolling in mice.


The tree species pool of Amazonian wetland forests: Which species can assemble in periodically waterlogged habitats?
We determined the filtered tree species pool of Amazonian wetland forests, based on confirmed occurrence records, to better understand how tree diversity in wetland environments compares to tree diversity in the entire Amazon region. The tree species pool was determined using data from two main sources: 1) a compilation of published tree species lists plus one unpublished list of our own, derived from tree plot inventories and floristic surveys; 2) queries on botanical collections that include Amazonian flora, curated by herbaria and available through the SpeciesLink digital biodiversity database. We applied taxonomic name resolution and determined sample-based species accumulation curves for both datasets, to estimate sampling effort and predict the expected species richness using Chao's analytical estimators. We report a total of 3 615 valid tree species occurring in Amazonian wetland forests. After surveying almost 70 years of research efforts to inventory the diversity of Amazonian wetland trees, we found that 74% these records were registered in published species lists (2 688 tree species). Tree species richness estimates predicted from either single dataset underestimated the total pooled species richness recorded as occurring in Amazonian wetlands, with only 41% of the species shared by both datasets. The filtered tree species pool of Amazonian wetland forests comprises 53% of the 6 727 tree species taxonomically confirmed for the Amazonian tree flora to date. This large proportion is likely to be the result of significant species interchange among forest habitats within the Amazon region, as well as in situ speciation processes due to strong ecological filtering. The provided tree species pool raises the number of tree species previously reported as occurring in Amazonian wetlands by a factor of 3.2.


IgG4-related renal disease: clinical and pathological characteristics.
IgG4-related disease is a recently established systemic condition. Tubulointerstitial nephritis is the most common renal manifestation. Glomerular lesions, particularly membranous glomerulonephritis, can develop simultaneously. Some patients present with serological renal dysfunction associated with elevated IgG or IgE levels and hypocomplementemia, while others are incidentally found to have abnormalities in kidneys on imaging. A majority of patients with IgG4-related kidney disease have similar lesions at other anatomical sites, which help us to suspect this condition. Serum IgG4 elevation (>135 mg/dL) is the most, although not entirely, specific marker for the diagnosis. Imaging findings varies from small nodules to bilateral diffuse abnormalities. In addition to the renal parenchyma, the renal pelvis and perirenal adipose tissue can be affected. Histological features include dense lymphoplasmacytic infiltration, storiform or "bird's eye" fibrosis (highlighted by PAM stain), and IgG4-positive plasma cell infiltration (>10 cells/high-power field and IgG4/IgG-positive cell ratio >40%). Immune complex deposition is detectable in the tubular basement membrane by immunofluorescence and/or electron microscopy. Patients usually respond well to corticosteroids, but highly active diseases may require other immunosuppressive therapies. Further investigations will be required to fully understand pathophysiology underlying this emerging condition.


Atypical resting-state functional connectivity of affective pain regions in chronic migraine.
Chronic migraineurs (CM) have painful intolerances to somatosensory, visual, olfactory, and auditory stimuli during and between migraine attacks. These intolerances are suggestive of atypical affective responses to potentially noxious stimuli. We hypothesized that atypical resting-state functional connectivity (rs-fc) of affective pain-processing brain regions may associate with these intolerances. This study compared rs-fc of affective pain-processing regions in CM with controls. Twelve minutes of resting-state blood oxygenation level-dependent data were collected from 20 interictal adult CM and 20 controls. Rs-fc between 5 affective regions (anterior cingulate cortex, right/left anterior insula, and right/left amygdala) with the rest of the brain was determined. Functional connections consistently differing between CM and controls were identified using summary analyses. Correlations between number of migraine years and the strengths of functional connections that consistently differed between CM and controls were calculated. Functional connections with affective pain regions that differed in CM and controls included regions in anterior insula, amygdala, pulvinar, mediodorsal thalamus, middle temporal cortex, and periaqueductal gray. There were significant correlations between the number of years with CM and functional connectivity strength between the anterior insula with mediodorsal thalamus and anterior insula with periaqueductal gray. CM is associated with interictal atypical rs-fc of affective pain regions with pain-facilitating and pain-inhibiting regions that participate in sensory-discriminative, cognitive, and integrative domains of the pain experience. Atypical rs-fc with affective pain regions may relate to aberrant affective pain processing and atypical affective responses to painful stimuli characteristic of CM.


Ethics-sensitivity of the Ghana national integrated strategic response plan for pandemic influenza.
Many commentators call for a more ethical approach to planning for influenza pandemics. In the developed world, some pandemic preparedness plans have already been examined from an ethical viewpoint. This paper assesses the attention given to ethics issues by the Ghana National Integrated Strategic Plan for Pandemic Influenza (NISPPI). We critically analyzed the Ghana NISPPI's sensitivity to ethics issues to determine how well it reflects ethical commitments and principles identified in our review of global pandemic preparedness literature, existing pandemic plans, and relevant ethics frameworks. This paper reveals that important ethical issues have not been addressed in the Ghana NISPPI. Several important ethical issues are unanticipated, unacknowledged, and unplanned for. These include guidelines on allocation of scarce resources, the duties of healthcare workers, ethics-sensitive operational guidelines/protocols, and compensation programs. The NISPPI also pays scant attention to use of vaccines and antivirals, border issues and cooperation with neighboring countries, justification for delineated actions, and outbreak simulations. Feedback and communication plans are nebulous, while leadership, coordination, and budgeting are quite detailed. With respect to presentation, the NISPPI's text is organized around five thematic areas. While each area implicates ethical issues, NISPPI treatment of these areas consistently fails to address them. Our analysis reveals a lack of consideration of ethics by the NISPPI. We contend that, while the plan's content and fundamental assumptions provide support for implementation of the delineated public health actions, its consideration of ethical issues is poor. Deficiencies include a failure to incorporate guidelines that ensure fair distribution of scarce resources and a lack of justification for delineated procedures. Until these deficiencies are recognized and addressed, Ghana runs the risk of rolling out unjust and ethically indefensible actions with real negative effects in the event of a pandemic. Soliciting inputs from the public and consultation with ethicists during the next revision of the NISPPI will be useful in addressing these issues.


Acetaminophen induces human neuroblastoma cell death through NFKB activation.
Neuroblastoma resistance to apoptosis may contribute to the aggressive behavior of this tumor. Therefore, it would be relevant to activate endogenous cellular death mechanisms as a way to improve neuroblastoma therapy. We used the neuroblastoma SH-SY5Y cell line as a model to study the mechanisms involved in acetaminophen (AAP)-mediated toxicity by measuring CYP2E1 enzymatic activity, NFkB p65 subunit activation and translocation to the nucleus, Bax accumulation into the mitochondria, cytochrome c release and caspase activation. AAP activates the intrinsic death pathway in the SH-SY5Y human neuroblastoma cell line. AAP metabolism is partially responsible for this activation, because blockade of the cytochrome CYP2E1 significantly reduced but did not totally prevent, AAP-induced SH-SY5Y cell death. AAP also induced NFkB p65 activation by phosphorylation and its translocation to the nucleus, where NFkB p65 increased IL-1β production. This increase contributed to neuroblastoma cell death through a mechanism involving Bax accumulation into the mitochondria, cytochrome c release and caspase3 activation. Blockade of NFkB translocation to the nucleus by the peptide SN50 prevented AAP-mediated cell death and IL-1β production. Moreover, overexpression of the antiapoptotic protein Bcl-x(L) did not decrease AAP-mediated IL-1β production, but prevented both AAP and IL-1β-mediated cell death. We also confirmed the AAP toxic actions on SK-N-MC neuroepithelioma and U87MG glioblastoma cell lines. The results presented here suggest that AAP activates the intrinsic death pathway in neuroblastoma cells through a mechanism involving NFkB and IL-1β.


Mid-Infrared Tunable Resonant Cavity Enhanced Detectors.
Mid-infrared detectors that are sensitive only in a tunable narrow spectral band are presented. They are based on the Resonant Cavity Enhanced Detector (RCED) principle and employing a thin active region using IV-VI narrow gap semiconductor layers. A Fabry-Pérot cavity is formed by two mirrors. The active layer is grown onto one mirror, while the second mirror can be displaced. This changes the cavity length thus shifting the resonances where the detector is sensitive. Using electrostatically actuated MEMS micromirrors, a very compact tunable detector system has been fabricated. Mirror movements of more than 3 μm at 30V are obtained. With these mirrors, detectors with a wavelength tuning range of about 0.7 μm have been realized. Single detectors can be used in mid-infrared micro spectrometers, while a detector arrangement in an array makes it possible to realize Adaptive Focal Plane Arrays (AFPA).


Ab initio investigation of the formation mechanism of nano-interfaces between 3d-late transition-metals and ZrO2 nanoclusters.
Understanding the formation of nano-interfaces between metallic clusters and nanoscale metal-oxides is an important step towards using such systems for catalytic applications. Thus, in this work, we employ density functional theory calculations to study the TMn-(ZrO2)13 interactions, for TM = Fe, Co, Ni, or Cu, and n = 1, 4, and 8. We found a general trend for adsorption and interaction energies (ad/int) for all cluster sizes, with . In terms of size effects, both adsorption and interaction (frozen adsorbed structures) energies become stronger with increasing cluster sizes due to the increase in the number of TM atoms in direct contact with the (ZrO2)13 nanocluster. The structural and electronic properties change for each TMn/(ZrO2)13 system, indicating that these properties could be tuned through variables like the TM species, cluster size and morphology (isomers with different structures). The results also indicate that, from the studied TMs, Ni (Cu) should form the smallest (largest) clusters when supported on the (ZrO2)13 nanoclusters. These and other results discussed here help understand the formation of the nano-interface in the TM-ZrO2 systems, which can be useful in the development of new catalysts.


Distribution of erythropoietin producing cells in rat kidneys during hypoxic hypoxia.
We have used in situ hybridization to determine the localization and distribution of cells expressing the erythropoietin (EPO) gene in kidneys of rats exposed to reduced oxygen tensions to characterize the control of renal EPO formation during hypoxic hypoxia. Animals were subjected to severe hypoxia (7.5% O2) for 4, 8 and 32 hours to assess changes related to the duration of hypoxic exposure, and additionally to 9% and 11.5% O2 for eight hours to define changes related to the degree of hypoxia. The number of cells containing EPO mRNA were counted on tissue sections and compared to tissue concentrations of EPO mRNA and to the serum hormone concentrations. In situ hybridization revealed expression of the EPO gene exclusively in peritubular cells that were predominantly located in the cortical labyrinth under all conditions tested. After four hours of severe hypoxia (7.5% O2) approximately 170-fold more cells were found to contain EPO mRNA than under normoxic conditions. The number of EPO producing cells did not change significantly between four and eight hours exposure to 7.5% O2, but the amount of EPO mRNA per kidney increased approximately threefold. Further continuation of hypoxia resulted in down-regulation of renal EPO mRNA levels, which was mainly due to a reduction in the number of cells containing EPO mRNA. Comparison of graded degrees of hypoxia applied for eight hours showed an inverse exponential relationship between oxygen tension and the number of EPO producing cells. This recruitment of cells expressing the EPO gene occurred along a gradient extending from the corticomedullary border to the subcapsular tissue.(ABSTRACT TRUNCATED AT 250 WORDS)


Protein A-conjugated iron oxide nanoparticles for separation of Vibrio cholerae from water samples.
Pathogen separation is of great significance for precise detection and prevention of disease outbreaks. For the first time, protein A conjugated with chitosan-coated iron oxide nanoparticles was prepared for pathogen separation at low concentrations from liquid samples. Vibrio cholerae O1 (VO1) bacteria were used for testing the effectiveness of this conjugate. Transmission electron microscopy (TEM) was used to confirm the presence of captured VO1. The results showed that, after binding with a specific antibody, the conjugate allows separation of VO1 bacteria from water samples at a concentration as low as 10 cfu mL(-1). Moreover, the conjugate can be used in parallel with conventional or modern diagnostic tests for quick and accurate detection of pathogens.


iNALU: Improved Neural Arithmetic Logic Unit.
Neural networks have to capture mathematical relationships in order to learn various tasks. They approximate these relations implicitly and therefore often do not generalize well. The recently proposed Neural Arithmetic Logic Unit (NALU) is a novel neural architecture which is able to explicitly represent the mathematical relationships by the units of the network to learn operations such as summation, subtraction or multiplication. Although NALUs have been shown to perform well on various downstream tasks, an in-depth analysis reveals practical shortcomings by design, such as the inability to multiply or divide negative input values or training stability issues for deeper networks. We address these issues and propose an improved model architecture. We evaluate our model empirically in various settings from learning basic arithmetic operations to more complex functions. Our experiments indicate that our model solves stability issues and outperforms the original NALU model in means of arithmetic precision and convergence.


Abnormalities of AMPK activation and glucose uptake in cultured skeletal muscle cells from individuals with chronic fatigue syndrome.
Post exertional muscle fatigue is a key feature in Chronic Fatigue Syndrome (CFS). Abnormalities of skeletal muscle function have been identified in some but not all patients with CFS. To try to limit potential confounders that might contribute to this clinical heterogeneity, we developed a novel in vitro system that allows comparison of AMP kinase (AMPK) activation and metabolic responses to exercise in cultured skeletal muscle cells from CFS patients and control subjects. Skeletal muscle cell cultures were established from 10 subjects with CFS and 7 age-matched controls, subjected to electrical pulse stimulation (EPS) for up to 24h and examined for changes associated with exercise. In the basal state, CFS cultures showed increased myogenin expression but decreased IL6 secretion during differentiation compared with control cultures. Control cultures subjected to 16 h EPS showed a significant increase in both AMPK phosphorylation and glucose uptake compared with unstimulated cells. In contrast, CFS cultures showed no increase in AMPK phosphorylation or glucose uptake after 16 h EPS. However, glucose uptake remained responsive to insulin in the CFS cells pointing to an exercise-related defect. IL6 secretion in response to EPS was significantly reduced in CFS compared with control cultures at all time points measured. EPS is an effective model for eliciting muscle contraction and the metabolic changes associated with exercise in cultured skeletal muscle cells. We found four main differences in cultured skeletal muscle cells from subjects with CFS; increased myogenin expression in the basal state, impaired activation of AMPK, impaired stimulation of glucose uptake and diminished release of IL6. The retention of these differences in cultured muscle cells from CFS subjects points to a genetic/epigenetic mechanism, and provides a system to identify novel therapeutic targets.


Adulthood transitions in health and welfare; a literature review.
The aim of the literature review was to describe how adulthood transition is used in health and welfare. A qualitative design with a deductive approach were used. As material, 283 articles published in scientific journals, between 2011-August 2013, were selected. The search was conducted August 2013. The data were analysed and sorted in a categorization matrix. Transition was identified as a process mainly related to the four types previously identified; developmental, situational, health-illness and organizational transitions. Another one transition was also identified, lifestyle transition.


Experimental gentamicin nephrotoxicity and agents that modify it: a mini-review of recent research.
The aminoglycoside antibiotic gentamicin (GM) is still widely used against infections by Gram-positive and Gram-negative aerobic bacteria. Its therapeutic efficacy, however, is limited by renal impairment that occurs in up to 30% of treated patients. The drug may accumulate in epithelial tubular cells causing a range of effects starting with loss of the brush border in epithelial cells and ending in overt tubular necrosis, activation of apoptosis and massive proteolysis. GM also causes cell death by generation of free radicals, phospholipidosis, extracellular calcium-sensing receptor stimulation and energetic catastrophe, reduced renal blood flow and inflammation. Many drugs have been shown to either ameliorate or potentiate GM nephrotoxicity. This article aims at updating the literature that has been published in the past decade on the effects of agents that either ameliorate or augment the nephrotoxicity of this aminoglycoside. Notable among the new ameliorating procedures are gene therapy, such as intravenous cell therapy with serum amyloid A protein-programmed cells, and the use of some novel antioxidant agents and oils of natural origin. These include, for example, green tea, garlic saffron, grape seed extracts as well as sesame and oleanolic oils. Agents that may augment GM nephrotoxicity include indomethacin, cyclosporin, uric acid and the Ca(++) -channel blocker verapamil. Most of the nephroprotective agents mentioned here have not been tested in large controlled clinical trials. Because of their relative safety and effectiveness, antioxidant agents seem to be good candidates for testing in humans.


The contingency of contingent valuation. How much are people willing to pay against Alzheimer's disease?
The present work focuses on the choice of the elicitation technique within a contingent valuation (CV) framework. We simultaneously apply three different elicitation techniques to elicit willingness-to-pay (WTP) values for three programs against Alzheimer's disease. First, the dichotomous choice approach is used, which is the standard procedure. However, giving respondents only a yes/no response alternative seems to result in overestimated WTP values. Therefore, we secondly apply the dissonance-minimizing format which screens respondents for their preferences and thus avoids possible yea-saying and protest answers against the payment vehicle. The third format, a modified version of the payment card, allows respondents to express a level of voting certainty and to make less of a commitment. With our findings we show that a well-designed CV method is a suitable instrument for helping decision makers in the health care sector and that the Swiss population favors highly a program which improves the situation of informal caregivers.


Forkhead Box Protein P1 Is Dispensable for Retina but Essential for Lens Development.
Forkhead box protein P1 (Foxp1) is a transcriptional repressor expressed in many tissues. We identified Foxp1 as a highly expressed gene in retinal progenitor cells and investigated its roles during eye development. Mouse eyes with Foxp1 gain- or loss-of-function were established in vitro and in vivo. Foxp1 overexpression in retinal progenitor cells resulted in reduced rod and increased cone photoreceptors. However, retina-specific knockout of Foxp1 was not associated with retinal differentiation abnormalities. Foxp1 was highly expressed in the lens during early development, and continued to be expressed in epithelial and cortical fiber cells until adulthood. At birth, analyses of Foxp1 lens-specific knockout (Foxp1-L-CKO) mice showed no gross morphologic changes in germinal or central epithelial cell compared to the controls. However, the numbers of proliferating and apoptotic cells were significantly increased in Foxp1-L-CKO mice. In addition, clear Y-structures were not observed in either the posterior or anterior sutures of the Foxp1-L-CKO lenses. Mature lenses of Foxp1-L-CKO mice were small and opaque. The fiber cell structure in the core and the cortical fiber cell columns were disturbed in Foxp1-L-CKO mice at postnatal day 14, potentially accounting for the opacity. In addition, epithelial cells were not aligned into columns along the transition zone in Foxp1-L-CKO mice. Taken together, these results suggest that Foxp1 has a role during lens growth in epithelial and differentiating fiber cells. Loss of Foxp1 results in loss of suture and fiber cell alignment, which eventually causes lens opacity, suggesting that Foxp1 has a key role in establishing cortical lens architecture.


HmbR outer membrane receptors of pathogenic Neisseria spp.: iron-regulated, hemoglobin-binding proteins with a high level of primary structure conservation.
We have recently cloned and characterized the hemoglobin receptor gene from Neisseria meningitidis serogroup C. N. meningitidis cells expressing HmbR protein were able to bind biotinylated hemoglobin, and the binding was specifically inhibited by unlabeled hemoglobin and not heme. The HmbR-mediated hemoglobin binding activity of N. meningitidis cells was shown to be iron regulated. The presence of hemoglobin but not heme in the growth medium stimulated HmbR-mediated hemoglobin binding activity. The efficiency of utilization of different hemoglobins by the HmbR-expressing N. meningitidis cells was shown to be species specific; human hemoglobin was the best source of iron, followed by horse, rat, turkey, dog, mouse, and sheep hemoglobins, The phenotypic characterization of HmbR mutants of some clinical strains of N. meningitidis suggested the existence of two unrelated hemoglobin receptors. The HmbR-unrelated hemoglobin receptor was shown to be identical to Hpu, the hemoglobin-haptoglobin receptor of N. meningitidis. The Hpu-dependent hemoglobin utilization system was not able to distinguish between different sources of hemoglobin; all animal hemoglobins were utilized equally well. HmbR-like genes are also present in N. meningitidis serogroups A and B, Neisseria gonorrhoeae MS11 and FA19, Neisseria perflava, and Neisseria polysaccharea. The hemoglobin receptor genes from N. meningitidis serogroups A and B and N. gonorrhoeae MS11 were cloned, and their nucleotide sequences were determined. The nucleotide sequence identity ranged between 86.5% (for N. meningitidis serogroup B hmbR and MS11 hmbR) and 93.4% (for N. meningitidis serogroup B hmbR and N. meningitidis serogroup C hmbR). The deduced amino acid sequences of these neisserial hemoglobin receptors were also highly related, with overall 84.7% conserved amino acid residues. A stop codon was found in the hmbR gene of N. gonorrhoeae MS11. This strain was still able to use hemoglobin and hemoglobin-haptoglobin complexes as iron sources, indicating that some gonococci may express only the HmbR-independent hemoglobin utilization system.


Ocular toxicity of low-molecular-weight components of silicone and fluorosilicone oils.
Silicone oil (SiO) and fluorosilicone oil (FSiO) are injected into the vitreous cavity in difficult cases of retinal detachment surgery. SiO and FSiO contain linear and cyclic low-molecular-weight components (LMWC) that are thought to cause ocular toxicity. Using the purified oils (without LMWC) and some of the individual LMWC, the authors evaluated the relation of the LMWC to the short-term ocular toxicity of the oils. When octamethylcyclotetrasiloxane or other single small species of linear and cyclic LMWC of SiO were injected into the rabbit anterior chamber, severe inflammation and corneal edema were induced. The ocular responses to the single species of the LMWC of SiO decreased with an increase of the molecular weights. Cyclic LMWC of FSiO (a mixture of trimethyl-3,3,3-trifluoropropylcyclotrisiloxane and tetramethyl-3,3,3-trifluoropropylcyclotetrasiloxane) also induced inflammation and corneal edema. However, unpurified SiO and FSiO, as well as purified oils (via solvent fractionation), did not cause significant adverse ocular response, presumably because the amounts of LMWC (especially the smallest species) in the oils were relatively small. Using gas chromatography, the authors analyzed SiO and FSiO recovered from rabbit and human vitreous cavities up to 2 yr after injection. In most of the cases, the concentrations of LMWC in SiO decreased after injection. This is consistent with the possibility that LMWC diffused from the oils into the ocular tissues. The long-term effect of LMWC in intraocular SiO and FSiO has not been determined. However, diffusion of LMWC into ocular tissues may relate to the chronic ocular toxicity of the oils.


Impact of ROS-Induced Damage of TCA Cycle Enzymes on Metabolism and Virulence of Salmonella enterica serovar Typhimurium.
Salmonella enterica serovar Typhimurium (STM) is exposed to reactive oxygen species (ROS) originating from aerobic respiration, antibiotic treatment, and the oxidative burst occurring inside the Salmonella-containing vacuole (SCV) within host cells. ROS damage cellular compounds, thereby impairing bacterial viability and inducing cell death. Proteins containing iron-sulfur (Fe-S) clusters are particularly sensitive and become non-functional upon oxidation. Comprising five enzymes with Fe-S clusters, the TCA cycle is a pathway most sensitive toward ROS. To test the impact of ROS-mediated metabolic perturbations on bacterial physiology, we analyzed the proteomic and metabolic profile of STM deficient in both cytosolic superoxide dismutases (ΔsodAB). Incapable of detoxifying superoxide anions (SOA), endogenously generated SOA accumulate during growth. ΔsodAB showed reduced abundance of aconitases, leading to a metabolic profile similar to that of an aconitase-deficient strain (ΔacnAB). Furthermore, we determined a decreased expression of acnA in STM ΔsodAB. While intracellular proliferation in RAW264.7 macrophages and survival of methyl viologen treatment were not reduced for STM ΔacnAB, proteomic profiling revealed enhanced stress response. We conclude that ROS-mediated reduced expression and damage of aconitase does not impair bacterial viability or virulence, but might increase ROS amounts in STM, which reinforces the bactericidal effects of antibiotic treatment and immune responses of the host.


Optical super-resolution by subtraction of time-gated images.
Applying image subtraction strategy together with time-gated detection, we can reveal finer details in a fixed cell sample using moderate light intensities. The subtractive imaging is obtained from the subtraction of a suitably weighted short lifetime intensity-image from a long lifetime one, while the weight coefficient can be selected using the analysis of an optical transfer function. Compared with other subtractive methods, ours is regarded as an optimized variation of gated stimulated emission depletion microscopy and can be implemented in a simpler manner, providing lateral super-resolution, and it is theoretically possible to further expand its application scope.


Premature Mortality, Risk Factors, and Causes of Death Following Childhood-Onset Neurological Impairments: A Systematic Review.
Background: Neurological impairment (NI) and disability are associated with reduced life expectancy, but the risk and magnitude of premature mortality in children vary considerably across study settings. We conducted a systematic review to estimate the magnitude of premature mortality following childhood-onset NI worldwide and to summarize known risk factors and causes of death. Methods: We searched various databases for published studies from their inception up to 31st October 2020. We included all cohort studies that assessed the overall risk of mortality in individuals with childhood-onset epilepsy, intellectual disability (ID), and deficits in hearing, vision and motor functions. Comparative measures of mortality such as the standardized mortality ratio (SMR), risk factors and causes were synthesized quantitatively under each domain of impairment. This review is registered on the PROSPERO database (registration number CRD42019119239). Results: The search identified 2,159 studies, of which 24 studies were included in the final synthesis. Twenty-two (91.7%) studies originated from high-income countries (HICs). The median SMR was higher for epilepsy compared with ID (7.1 [range 3.1-22.4] vs. 2.9 [range 2.0-11.6]). In epilepsy, mortality was highest among younger age groups, comorbid neurological disorders, generalized seizures (at univariable levels), untreatable epilepsy, soon after diagnosis and among cases with structural/metabolic types, but there were no differences by sex. Most deaths (87.5%) were caused by non-epilepsy-related causes. For ID, mortality was highest in younger age groups and girls had a higher risk compared to the general population. Important risk factors for premature mortality were severe-to-profound severity, congenital disorders e.g., Down Syndrome, comorbid neurological disorders and adverse pregnancy and perinatal events. Respiratory infections and comorbid neurological disorders were the leading causes of death in ID. Mortality is infrequently examined in impairments of vision, hearing and motor functions. Summary: The risk of premature mortality is elevated in individuals with childhood-onset NI, particularly in epilepsy and lower in ID, with a need for more studies for vision, hearing, and motor impairments. Survival in NI could be improved through interventions targeting modifiable risk factors and underlying causes.


Optimizing outcomes for GLP-1 agonists.
The management of type 2 diabetes mellitus and, in particular, blood glucose levels can be complex and challenging for physicians and patients. Many patients are frustrated with the agents currently available because they have associated limitations of weight gain, hypoglycemia, and tolerability issues. Advantages of glucagon-like peptide-1 (GLP-1) agonists include their efficacy in lowering blood glucose levels, their lack of association with weight gain, and their indirect association with weight loss. Patients likely to benefit from GLP-1 agonist therapy are those in the early stages of the disease and those in need of sufficient benefit from an agent with good efficacy. Setting appropriate expectations for patients is important, as well as explaining the significance of glucose control and reminding patients that this is the main goal of therapy. Patients (and physicians) who have concerns about hypoglycemia can be reassured that GLP-1 agonists work only in the presence of hyperglycemia. Longer-acting GLP-1 agonists are dosed less frequently, appear to be associated with less nausea, and may be associated with better rates of adherence than shorter-acting agents. When initiating therapy with GLP-1 agonists, doses should be gradually escalated to minimize gastrointestinal adverse effects. The dose of a sulfonylurea may need to be lowered if a GLP-1 agonist is added. A review of possible adverse effects, contraindications, dosing and administration techniques, and expected benefits of therapy is provided in the present article to optimize success rates with this new class of agents.


Neural reactivity to rewards and losses in offspring of mothers and fathers with histories of depressive and anxiety disorders.
Depression appears to be characterized by reduced neural reactivity to receipt of reward. Despite evidence of shared etiologies and high rates of comorbidity between depression and anxiety, this abnormality may be relatively specific to depression. However, it is unclear whether children at risk for depression also exhibit abnormal reward responding, and if so, whether risk for anxiety moderates this association. The feedback negativity (FN) is an event-related potential component sensitive to receipt of rewards versus losses that is reduced in depression. Using a large community sample (N = 407) of 9-year-old children who had never experienced a depressive episode, we examined whether histories of depression and anxiety in their parents were associated with the FN following monetary rewards and losses. Results indicated that maternal history of depression was associated with a blunted FN in offspring, but only when there was no maternal history of anxiety. In addition, greater severity of maternal depression was associated with greater blunting of the FN in children. No effects of paternal psychopathology were observed. Results suggest that blunted reactivity to rewards versus losses may be a vulnerability marker that is specific to pure depression, but is not evident when there is also familial risk for anxiety. In addition, these findings suggest that abnormal reward responding is evident as early as middle childhood, several years prior to the sharp increase in the prevalence of depression and rapid changes in neural reward circuitry in adolescence.


Use of dexmedetomidine for prophylactic analgesia and sedation in delayed extubation patients after craniotomy: a study protocol and statistical analysis plan for a randomized controlled trial.
Pain and agitation are common in patients after craniotomy. They can result in tachycardia, hypertension, immunosuppression, increased catecholamine production and increased oxygen consumption. Dexmedetomidine, an alpha-2 agonist, provides adequate sedation without respiratory depression, while facilitating frequent neurological evaluation. The study is a prospective, randomized, double-blind, controlled, parallel-group design. Consecutive patients are randomly assigned to one of the two treatment study groups, labeled 'Dex group' or 'Saline group.' Dexmedetomidine group patients receive a continuous infusion of 0.6 μg/kg/h (10 ug/ml). Placebo group patients receive a maintenance infusion of 0.9% sodium chloride for injection at a volume and rate equal to that of dexmedetomidine. The mean percentages of time in optimal sedation, vital signs, various and adverse events, the percentage of patients requiring propofol for rescue to achieve/maintain targeted sedation (Sedation-Agitation Scale, SAS 3 to 4) and total dose of propofol required throughout the study drug infusion are collected. The percentage of patients requiring fentanyl for additional rescue to analgesia and total dose of fentanyl required are recorded. The effects of dexmedetomidine on hemodynamic and recovery responses during extubation are measured. Intensive care unit and hospital length of stay also are collected. Plasma levels of epinephrine, norepinephrine, dopamine, cortisol, neuron-specific enolase and S100-B are measured before infusion (T1), at two hours (T2), four hours (T3) and eight hours (T4) after infusion and at the end of infusion (T5) in 20 patients in each group. The study has been initiated as planned in July 2012. One interim analysis advised continuation of the trial. The study will be completed in July 2013. ClinicalTrials (NCT): ChiCTR-PRC-12002903.


The efficacy of motivational interviewing as a brief intervention for excessive drinking: a meta-analytic review.
(1) To examine whether or not motivational interviewing (MI) is more efficacious than no intervention in reducing alcohol consumption; (2) to examine whether or not MI is as efficacious as other interventions. A literature search followed by a meta-analytic review of randomized control trials of MI interventions. Aggregated between-group effect sizes and confidence intervals were calculated for each study. Literature search revealed 22 relevant studies, of which nine compared brief MI with no treatment, and met methodological criteria for inclusion. In these, the aggregate effect size was 0.18 (95% C.I. 0.07, 0.29), but was greater 0.60 (95% C.I. 0.36, 0.83) when, in a post-hoc analysis, the follow-up period was three months or less. Its efficacy also increased when dependent drinkers were excluded. There were nine studies meeting methodological criteria for inclusion which compared brief MI with another treatment (one of a diverse set of interventions), yielding an aggregate effect size of 0.43(95% C.I. 0.17, 0.70). The literature review pointed to several factors which may influence MI's long-term efficacy effectiveness of MI. Brief MI is effective. Future studies should focus on possible predictors of efficacy such as gender, age, employment status, marital status, mental health, initial expectations, readiness to change, and whether the population is drawn from treatment-seeking or non-treatment-seeking populations. Also, the components of MI should be compared to determine which are most responsible for maintaining long-term changes.


LcrD, a membrane-bound regulator of the Yersinia pestis low-calcium response.
Yersinia pestis, the etiologic agent of bubonic plague, contains a 75-kb virulence plasmid, called pCD1 in Y. pestis KIM. The low-Ca(2+)-response genes of Y. pestis regulate both bacterial growth and the expression of pCD1-encoded virulence determinants in response to temperature and the presence of Ca2+ or nucleotides. This study characterizes the nucleotide sequence and protein product of the lcrD locus. An lcrD mutant, in contrast to the parent Y. pestis, did not undergo growth restriction or induce strong expression of the V antigen when grown under conditions (37 degrees C, no Ca2+) expected to elicit maximal expression of pCD1 genes. DNA sequence analysis of the cloned lcrD locus showed a single open reading frame that could encode a protein with a molecular weight of 77,804 and a pI of 4.88. LcrD was identified as a 70-kDa inner membrane protein by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblot analysis. LcrD membrane topology was investigated by using lcrD-phoA translational fusions generated with the transposon TnphoA. The alkaline phosphatase activities of the resultant hybrid proteins were consistent with a model predicting eight amino-terminal transmembrane segments that anchor a large cytoplasmic carboxyl-terminal domain to the inner membrane.


Results of an effort to integrate quality and safety into medical and nursing school curricula and foster joint learning.
Improvements in health care are slow, in part because doctors and nurses lack skills in quality improvement, patient safety, and interprofessional teamwork. This article reports on the Retooling for Quality and Safety initiative of the Josiah Macy Jr. Foundation and the Institute for Healthcare Improvement, which sought to integrate improvement and patient safety into medical and nursing school curricula. In one academic year, 2009-10, the initiative supported new learning activities (87 percent of which were interprofessional, involving both medical and nursing students) in classrooms, simulation centers, and clinical care settings that involved 1,374 student encounters at six universities. The work generated insights-described in this article-into which learning goals require interprofessional education; how to create clinically based improvement learning for all students; and how to demonstrate the effects on students' behavior, organizational practice, and benefits to patients. A commonly encountered limiting factor for the programs was the lack of a critical mass of clinically based faculty members who were ready to teach about the improvement of care. What's more, the paucity of robust evaluation strategies for such programs suggests a future research agenda that deserves to be funded.


The influence of protein fractions from bovine colostrum digested in vivo and in vitro on human intestinal epithelial cell proliferation.
Colostrum consists of a number of biologically active proteins and peptides that influence physiological function and development of a neonate. The present study investigated the biological activity of peptides released from first day bovine colostrum through in vitro and in vivo enzymatic digestion. This was assessed for proliferative activity using a human intestinal epithelial cell line, T84. Digestion of the protein fraction of bovine colostrum in vitro was conducted with the enzymes pepsin, chymosin and trypsin. Pepsin and chymosin digests yielded protein fractions with proliferative activity similar to that observed with undigested colostrum and the positive control foetal calf serum (FCS). In contrast trypsin digestion significantly (P<0·05) decreased colostral proliferative activity when co-cultured with cells when compared with undigested colostrum. The proliferative activity of undigested colostrum protein and abomasal whey protein digesta significantly increased (P<0·05) epithelial cell proliferation in comparison to a synthetic peptide mix. Bovine colostrum protein digested in vivo was collected from different regions of the gastrointestinal tract (GIT) in newborn calves fed either once (n=3 calves) or three times at 12-h intervals (n=3 calves). Digesta collected from the distal duodenum, jejunum and colon of calves fed once, significantly (P<0·05) stimulated cell proliferation in comparison with comparable samples collected from calves fed multiple times. These peptide enriched fractions are likely to yield candidate peptides with potential application for gastrointestinal repair in mammalian species.


Early adoption of the fluocinolone acetonide (FAc) intravitreal implant in patients with persistent or recurrent diabetic macular edema (DME).
Objective: To assess long-term outcomes for effectiveness, safety, and treatment burden after injection of 0.2 µg/day fluocinolone acetonide [FAc] intravitreal implant (ILUVIEN®) in patients with persistent or recurrent diabetic macular edema (DME) and 6-18 months of follow-up. Methods: Retrospective case series in 18 eyes (13 patients) treated with the FAc implant. Prior to the implant, eyes were treated with an anti-VEGF therapy, dexamethasone implant, or focal or panretinal photocoagulation. Effectiveness outcomes included changes in visual acuity and macular edema. Safety outcomes included intraocular pressure (IOP) changes, IOP drugs, and IOP-related surgeries/interventions. Treatment burden was assessed by comparing the number of DME treatments before and after FAc implantation. Results: The FAc implant reduced macular volume in 16/18 (89%) eyes, with a statistically significant mean change of -1.33 mm3 (p=0.001). The average central retinal thickness reduction for all 18 eyes was statistically significant, decreasing from 444 µm at baseline to 359 µm after the FAc implant (p<0.001). In 90% of eyes, visual acuity was stable throughout the follow-up period, with increases or no worsening in Early Treatment Diabetic Retinopathy Study letter score. Although mean IOP was statistically higher after treatment, it was within the normal range at all timepoints, and most (83.3%) eyes remained in the IOP category 0-22 mmHg, and the number of IOP treatments required did not increase and no patients required IOP-lowering surgery. Treatment burden for DME was reduced after the implant was administered, with 56% of eyes not requiring any additional treatment. The average number of treatments was 1.3 in the 6 months after the FAc implant versus 4.6 in the 12 months preceding the implant. Conclusion: The FAc implant is an appropriate option to incorporate earlier in the DME treatment process, leading to positive long-term outcomes with an acceptable safety profile, and a reduced treatment burden for patients, and reduced clinical staff time.


Effects of vegetated field borders on arthropods in cotton fields in eastern North Carolina.
The influence, if any, of 5m wide, feral, herbaceous field borders on pest and beneficial arthropods in commercial cotton, Gossypium hirsutum (L.) (Malvales: Malvaceae), fields was measured through a variety of sampling techniques over three years. In each year, 5 fields with managed, feral vegetation borders and five fields without such borders were examined. Sampling was stratified from the field border or edge in each field in an attempt to elucidate any edge effects that might have occurred. Early season thrips populations appeared to be unaffected by the presence of a border. Pitfall sampling disclosed no differences in ground-dwelling predaceous arthropods but did detect increased populations of crickets around fields with borders. Cotton aphid (Aphis gossypii Glover) (Hemiptera: Aphididae) populations were too low during the study to adequately assess border effects. Heliothines, Heliothis virescens (F.) and Helicoverpa zea (Boddie) (Lepidoptera: Noctuidae), egg numbers and damage rates were largely unaffected by the presence or absence of a border, although in one instance egg numbers were significantly lower in fields with borders. Overall, foliage-dwelling predaceous arthropods were somewhat more abundant in fields with borders than in fields without borders. Tarnished plant bugs, Lygus lineolaris (Palisot de Beauvois) (Heteroptera: Miridae) were significantly more abundant in fields with borders, but stink bugs, Acrosternum hilare (Say), and Euschistus servus (Say) (Hemiptera: Pentatomidae) numbers appeared to be largely unaffected by border treatment. Few taxa clearly exhibited distributional edge effects relative to the presence or absence of border vegetation. Field borders like those examined in this study likely will have little impact on insect pest management in cotton under current insect management regimens.


Abortion induces reactivation of inflammation in relapsing-remitting multiple sclerosis.
To investigate clinical and radiological outcomes of women with relapsing-remitting multiple sclerosis (RRMS) undergoing abortion. An independent, multicentre retrospective study was conducted collecting data from eight Italian MS centres. We compared the preconception and postabortion annualised relapse rate (ARR) and number of Gadolinium enhancing (Gd+) lesions, by analyses of covariance. Variables associated with postabortion clinical and MRI activity were investigated using Poisson regression models; each abortion was considered as a statistical unit. From 1995 to 2017, we observed 188 abortions (17 elective) in 153 women with RRMS. Abortions occurred after a mean time of 9.5 (4.4) weeks from estimated conception date. In 86 events out of 188, conception happened during treatment with disease modifying drugs. The mean postabortion ARR (0.63±0.74) was significantly increased (p=0.037) compared with the preconception year (0.50±0.71) as well as the postabortion mean number of new Gd+ lesions (0.77±1.40 vs 0.39±1.04; p=0.004). Higher likelihood of relapses was predicted by higher preconception ARR, discontinuation of preconception treatment and elective abortion; the occurrence of new Gd+ lesions was associated with higher preconception number of active lesions, discontinuation of preconception treatment, shorter length of pregnancy maintenance and elective abortion. Abortion was associated with clinical and radiological inflammatory rebound remarkably in the first 12 months postevent. Deregulated proinflammatory processes arising at the early stages of pregnancy might play a role both in MS reactivation and abortion. Women with MS should be counselled about these risks of abortion and followed up accordingly.


An algorithm to parse segment packing in predicted protein contact maps.
The analysis of correlation in alignments generates a matrix of predicted contacts between positions in the structure and while these can arise for many reasons, the simplest explanation is that the pair of residues are in contact in a three-dimensional structure and are affecting each others selection pressure. To analyse these data, A dynamic programming algorithm was developed for parsing secondary structure interactions in predicted contact maps. The non-local nature of the constraints required an iterated approach (using a "frozen approximation") but with good starting definitions, a single pass was usually sufficient. The method was shown to be effective when applied to the transmembrane class of protein and error tolerant even when the signal becomes degraded. In the globular class of protein, where the extent of interactions are more limited and more complex, the algorithm still behaved well, classifying most of the important interactions correctly in both a small and a large test case. For the larger protein, this involved examples of the algorithm apportioning parts of a single large secondary structure element between two different interactions. It is expected that the method will be useful as a pre-processor to coarse-grained modelling methods to extend the range of protein tertiary structure prediction to larger proteins or to data that is currently too 'noisy' to be used by current residue-based methods.