Membrane structure and its relation to haemolysis.
Advances in our understanding of the biochemistry, physiology and ultrastructure of the normal erythrocyte membrane have opened up the possibility of characterising congenital or acquired membrane defects in various haemolytic anaemias. The normal red cell membrane can undergo reversible disc-echinocytic or disc-stomatocytic shape changes in response to a wide variety of chemical agents and conditions. These shape changes may become irreversible and, in fact, they may be encountered in different types of haemolytic disease, suggesting that the echinocytic and stomatocytic shape changes represent two fundamental ways in which red cells react to intrinsic and extrinsic insults. Membrane alterations in haemolytic disease can be divided into disorders in which the defect appears to be a primary membrane abnormality, e.g. hereditary spherocytosis and disorders in which membrane damage occurs secondary to internal or external influences, e.g. the membrane alteration in sickled cells. The normal of deformability of the red cell is one of the prime determinants of survival in vivo and thus the geometric relationship of the erythrocyte surface area to cell volume, if decreased, can contribute to haemolysis. Intrinsic changes in membrane deformability or membrane deformability secondary to alterations in the cell haemoglobin may also compromise passage through the microcirculation, particularly through the spleen. Finally, abnormalities of cation permeability and/or lipid composition are found in certain haemolytic states. In each case it is essential to attempt to relate the abnormality described to the manner in which cell properties critical to in vivo survival are compromised in order to understand the pathophysiology.


Sarcopenia in Patients with Advanced Liver Disease.
Sarcopenia is the loss of muscle mass and function, affecting up to 70% of patients with advanced liver disease. Liver cirrhosis is characterized by an altered glucose metabolism, lipid oxidation, ketogenesis and protein catabolism, leading to the loss of adipose and muscle tissue. The gastrointestinal dysfunction of cirrhotic patients results in inadequate nutrients intake and is responsible for muscle weakness thus limiting physical exercise and perpetuating the reduction of muscle mass. Recently, alterations of hormonal pathways involved in muscle growth, increased intestinal permeability and changes in the gut microbiota composition have been reported in cirrhotic patients. Interestingly, a role of intestinal bacteria in maintaining muscle health has been hypothesized through the translocation of bacteria and bacterial products into the bloodstream triggering the production of muscle wasting-related cytokines. Sarcopenia is associated with severe outcomes in patients with liver cirrhosis, mostly due to the incidence of disease complications. Furthermore, sarcopenia may represent an important prognostic factor for patients with hepatocellular carcinoma and for those undergoing liver transplantation and can be considered a useful additional tool in the global assessment of patients with advanced liver disease.


A methodology for validating artifact removal techniques for physiological signals.
Artifact removal from physiological signals is an essential component of the biosignal processing pipeline. The need for powerful and robust methods for this process has become particularly acute as healthcare technology deployment undergoes transition from the current hospital-centric setting toward a wearable and ubiquitous monitoring environment. Currently, determining the relative efficacy and performance of the multiple artifact removal techniques available on real world data can be problematic, due to incomplete information on the uncorrupted desired signal. The majority of techniques are presently evaluated using simulated data, and therefore, the quality of the conclusions is contingent on the fidelity of the model used. Consequently, in the biomedical signal processing community, there is considerable focus on the generation and validation of appropriate signal models for use in artifact suppression. Most approaches rely on mathematical models which capture suitable approximations to the signal dynamics or underlying physiology and, therefore, introduce some uncertainty to subsequent predictions of algorithm performance. This paper describes a more empirical approach to the modeling of the desired signal that we demonstrate for functional brain monitoring tasks which allows for the procurement of a "ground truth" signal which is highly correlated to a true desired signal that has been contaminated with artifacts. The availability of this "ground truth," together with the corrupted signal, can then aid in determining the efficacy of selected artifact removal techniques. A number of commonly implemented artifact removal techniques were evaluated using the described methodology to validate the proposed novel test platform.


Theoretical considerations on programmatic assessment.
Introduction: Programmatic assessment (PA) is an approach to assessment aimed at optimizing learning which continues to gain educational momentum. However, the theoretical underpinnings of PA have not been clearly described. An explanation of the theoretical underpinnings of PA will allow educators to gain a better understanding of this approach and, perhaps, facilitate its use and effective implementation. The purpose of this article is twofold: first, to describe salient theoretical perspectives on PA; second to examine how theory may help educators to develop effective PA programs, helping to overcome challenges around PA.Results: We outline a number of learning theories that underpin key educational principles of PA: constructivist and social constructivist theory supporting meaning making, and longitudinality; cognitivist and cognitive development orientation scaffolding the practice of a continuous feedback process; theory of instructional design underpinning assessment as learning; self-determination theory (SDT), self-regulation learning theory (SRL), and principles of deliberate practice providing theoretical tenets for student agency and accountability.Conclusion: The construction of a plausible and coherent link between key educational principles of PA and learning theories should enable educators to pose new and important inquiries, reflect on their assessment practices and help overcome future challenges in the development and implementation of PA in their programs.


Mef2cb regulates late myocardial cell addition from a second heart field-like population of progenitors in zebrafish.
Two populations of cells, termed the first and second heart field, drive heart growth during chick and mouse development. The zebrafish has become a powerful model for vertebrate heart development, partly due to the evolutionary conservation of developmental pathways in this process. Here we provide evidence that the zebrafish possesses a conserved homolog to the murine second heart field. We developed a photoconversion assay to observe and quantify the dynamic late addition of myocardial cells to the zebrafish arterial pole. We define an extra-cardiac region immediately posterior to the arterial pole, which we term the late ventricular region. The late ventricular region has cardiogenic properties, expressing myocardial markers such as vmhc and nkx2.5, but does not express a full complement of differentiated cardiomyocyte markers, lacking myl7 expression. We show that mef2cb, a zebrafish homolog of the mouse second heart field marker Mef2c, is expressed in the late ventricular region, and is necessary for late myocardial addition to the arterial pole. FGF signaling after heart cone formation is necessary for mef2cb expression, the establishment of the late ventricular region, and late myocardial addition to the arterial pole. Our study demonstrates that zebrafish heart growth shows more similarities to murine heart growth than previously thought. Further, as congenital heart disease is often associated with defects in second heart field development, the embryological and genetic advantages of the zebrafish model can be applied to study the vertebrate second heart field.


Morphologic features and natural history of scalp nevi in children.
To characterize the clinical changes in clinically distinctive scalp nevi over time in children to help guide management and avoid misdiagnosis as melanoma. Cohort study. Washington University School of Medicine pediatric dermatology clinics. Patients Of 93 patients younger than 18 years with photographically documented, clinically distinctive scalp nevi, 28 (30%) consented to participate. Minimum follow-up from the initial visit was 1 year. Collectively, these patients had 44 scalp nevi at the initial visit. No patient had a personal diagnosis of melanoma or dysplastic nevus syndrome. Clinical changes in scalp nevi as determined using the ABCDE scoring system (ie, asymmetry, border irregularity, color variegation, diameter >6 mm, and evolution/elevation from initial to follow-up images) on initial and follow-up photographs of scalp nevi. Overall, 77% of the clinically distinctive scalp nevi (34 of 44) showed clinical signs of change during mean follow-up of 2.8 years. Of those with changes, 18 (53%) became more atypical and 16 (47%) became less atypical since the initial examination. None of the changes were concerning for melanoma. The mean total scalp nevus count was 2.6. Scalp nevi represented approximately 6% of total-body nevi. The number of scalp nevi increased with age. Boys had 1.5 times the number of scalp nevi as girls (P = .03). Scalp nevi are clinically dynamic in childhood. These changes include an increase or a decrease in atypical features and occur in all age groups. This preliminary study does not support excisional biopsies but does support physician evaluation of scalp nevi evolution and serial photography of clinically distinctive lesions.


Caveolin-1 promotes mitochondrial health and limits mitochondrial ROS through ROCK/AMPK regulation of basal mitophagic flux.
Caveolin-1 (CAV1), the main structural component of caveolae, is phosphorylated at tyrosine-14 (pCAV1), regulates signal transduction, mechanotransduction, and mitochondrial function, and plays contrasting roles in cancer progression. We report that CRISPR/Cas9 knockout (KO) of CAV1 increases mitochondrial oxidative phosphorylation, increases mitochondrial potential, and reduces ROS in MDA-MB-231 triple-negative breast cancer cells. Supporting a role for pCAV1, these effects are reversed upon expression of CAV1 phosphomimetic CAV1 Y14D but not non-phosphorylatable CAV1 Y14F. pCAV1 is a known effector of Rho-associated kinase (ROCK) signaling and ROCK1/2 signaling mediates CAV1 promotion of increased mitochondrial potential and decreased ROS production in MDA-MB-231 cells. CAV1/ROCK control of mitochondrial potential and ROS is caveolae-independent as similar results were observed in PC3 prostate cancer cells lacking caveolae. Increased mitochondrial health and reduced ROS in CAV1 KO MDA-MB-231 cells were reversed by knockdown of the autophagy protein ATG5, mitophagy regulator PINK1 or the mitochondrial fission protein Drp1 and therefore due to mitophagy. Use of the mitoKeima mitophagy probe confirmed that CAV1 signaling through ROCK inhibited basal mitophagic flux. Activation of AMPK, a major mitochondrial homeostasis protein inhibited by ROCK, is inhibited by CAV1-ROCK signaling and mediates the increased mitochondrial potential, decreased ROS, and decreased basal mitophagy flux observed in wild-type MDA-MB-231 cells. CAV1 regulation of mitochondrial health and ROS in cancer cells therefore occurs via ROCK-dependent inhibition of AMPK. This study therefore links pCAV1 signaling activity at the plasma membrane with its regulation of mitochondrial activity and cancer cell metabolism through control of mitophagy.


Anxiety Disorders in Old Age: Psychiatric Comorbidities, Quality of Life, and Prevalence According to Age, Gender, and Country.
Previous estimates of the prevalence of anxiety disorders in late life vary greatly due to the lack of reliable diagnostic tools. This MentDis_ICF65+ study assessed 12-month prevalence rates of anxiety disorders and age- and gender-related differences in comorbidities, as well as impact on quality of life. The study used a cross-sectional multicenter survey. The study sample comprised 3,142 men and women aged 65 to 84 years, living in five European countries and Israel. Anxiety disorders were assessed using computer-assisted face-to-face interviews with an age-appropriate diagnostic interview (CIDI65+). The prevalence of anxiety disorders was 17.2%. Agoraphobia was the most frequent disorder (4.9%), followed by panic disorder (3.8%), animal phobia (3.5%), general anxiety disorder (3.1%), post-traumatic stress disorder (1.4%), social phobia (1.3%), and obsessive-compulsive disorder (0.8%). The prevalence rate of any anxiety disorder dropped by 40% to 47% in adults aged 75-84 years compared with those aged 65-74 years. Women were twice as likely to present with agoraphobia or general anxiety disorder as men. Only panic disorder and phobia were associated with comorbid major depression. The negative relationship with quality of life was limited to agoraphobia and generalized anxiety disorder. The age-appropriate CIDI65+ led to higher prevalence rates of anxiety disorders in the elderly, yet to weaker associations with comorbidities and impaired quality of life compared with previous studies.


Conditions and procedures for in-hospital extracorporeal life support (ECLS) in cardiopulmonary resuscitation (CPR) of adult patients.
The use of extracorporeal life support (ECLS) in cardiopulmonary resuscitation (CPR; ECPR) has been repeatedly published as non-randomized studies, mainly case series and case reports. The aim of this article is to support physicians, perfusionists, nurses and extracorporeal membrane oxygenation (ECMO) specialists who regularly perform ECPR or are willing to start an ECPR program by establishing standards for safe and efficient ECPR procedures. This article represents the experience and recommendations of physicians who provide ECPR routinely. Based on its survival and outcome rates, ECPR can be considered when determining the optimal treatment of patients who require CPR. The successful performance of ECLS cannulation during CPR is a life-saving measure and has been associated with improved outcome (including neurological outcome) after CPR. We summarize the general structure of an ECLS team and describe the cannulation procedure and the approaches for post-resuscitation care. The differences in hospital organizations and their regulations may result in variations of this model.


A systematic review of the effectiveness of Chinese herbal medication in symptom management and improvement of quality of life in adult cancer patients.
The aim of this systematic review was to assess the effectiveness of Chinese medicinal herbs used concurrently with cancer treatments in terms primarily of toxicity management but also quality of life and survival in adult cancer patients. Forty-nine trials met the inclusion criteria and were reviewed according to standard processes of systematic reviews. These trials included 3992 patients. All studies with the exception of one were of low methodological quality. The vast majority of the studies have shown that Chinese medicinal herbs improved treatment side effects, quality of life, and performance status, and some have provided evidence of tumour regression and increased survival. While no clinical recommendations can derive from such low quality studies, the number of studies reporting positive results is high enough to suggest that Chinese medicinal herbs may have a role in cancer care. However, more methodologically rigorous studies need to be developed as a priority before any firm conclusions can be drawn.


Differentiation between Subtypes of Primary Progressive Aphasia by Using Cortical Thickness and Diffusion-Tensor MR Imaging Measures.
To test a multimodal magnetic resonance (MR) imaging-based approach composed of cortical thickness and white matter (WM) damage metrics to discriminate between variants of primary progressive aphasia (PPA) that are nonfluent and/or agrammatic (NFVPPA) and semantic (SVPPA). This study was approved by the local ethics committees on human studies, and written informed consent from all patients was obtained before their enrollment. T1-weighted and diffusion-tensor (DT) MR images were obtained from 13 NFVPPA patients, 13 SVPPA patients, and 23 healthy control participants. Cortical thickness and DT MR imaging indices from the long-associative and interhemispheric WM tracts were obtained. A random forest (RF) analysis was used to identify the image features associated with each clinical syndrome. Individual patient classification was performed by using receiver operator characteristic curve analysis with cortical thickness, DT MR imaging, and a combination of the two modalities. RESULTS RF analysis showed that the best markers to differentiate the two PPA variants at an individual patient level among cortical thickness and DT MR imaging metrics were diffusivity abnormalities of the left inferior longitudinal and uncinate fasciculi and cortical thickness measures of the left temporal pole and inferior frontal gyrus. A combination of cortical thickness and DT MR imaging measures (the so-called gray-matter-and-WM model) was able to distinguish patients with NFVPPA and SVPPA with the following classification pattern: area under the curve, 0.91; accuracy, 0.89; sensitivity, 0.92; specificity, 0.85. Leave-one-out analysis demonstrated that the gray matter and WM model is more robust than the single MR modality models to distinguish PPA variants (accuracy was 0.86, 0.73, and 0.68 for the gray matter and WM model, the gray matter-only model, and the WM-only model, respectively). A combination of structural and DT MR imaging metrics may provide a quantitative procedure to distinguish NFVPPA and SVPPA patients at an individual patient level. The discrimination accuracies obtained suggest that the gray matter and WM model is potentially relevant for the differential diagnosis of the PPA variants in clinical practice.


Herpes Simplex Virus 1 UL37 Protein Tyrosine Residues Conserved among All Alphaherpesviruses Are Required for Interactions with Glycoprotein K, Cytoplasmic Virion Envelopment, and Infectious Virus Production.
The herpes simplex virus 1 (HSV-1) UL37 protein functions in virion envelopment at trans-Golgi membranes, as well as in retrograde and anterograde transport of virion capsids. Recently, we reported that UL37 interacts with glycoprotein K (gK) and its interacting partner protein UL20 (N. Jambunathan, D. Chouljenko, P. Desai, A. S. Charles, R. Subramanian, V. N. Chouljenko, and K. G. Kousoulas, J Virol 88:5927-5935, 2014, http://dx.doi.org/10.1128/JVI.00278-14), facilitating cytoplasmic virion envelopment. Alignment of UL37 homologs encoded by alphaherpesviruses revealed the presence of highly conserved residues in the central portion of the UL37 protein. A cadre of nine UL37 site-specific mutations were produced and tested for their ability to inhibit virion envelopment and infectious virus production. Complementation analysis revealed that replacement of tyrosines 474 and 480 with alanine failed to complement the UL37-null virus, while all other mutated UL37 genes complemented the virus efficiently. The recombinant virus DC474-480 constructed with tyrosines 474, 476, 477, and 480 mutated to alanine residues produced a gK-null-like phenotype characterized by the production of very small plaques and accumulation of capsids in the cytoplasm of infected cells. Recombinant viruses having either tyrosine 476 or 477 replaced with alanine produced a wild-type phenotype. Immunoprecipitation assays revealed that replacement of all four tyrosines with alanines substantially reduced the ability of gK to interact with UL37. Alignment of HSV UL37 with the human cytomegalovirus and Epstein-Barr virus UL37 homologs revealed that Y480 was conserved only for alphaherpesviruses. Collectively, these results suggest that the UL37 conserved tyrosine 480 residue plays a crucial role in interactions with gK to facilitate cytoplasmic virion envelopment and infectious virus production. The HSV-1 UL37 protein is conserved among all herpesviruses, functions in both retrograde and anterograde transport of virion capsids, and plays critical roles in cytoplasmic virion envelopment by interacting with gK. We show here that UL37 tyrosine residues conserved among all alphaherpesviruses serve critical roles in cytoplasmic virion envelopment and interactions with gK.


Age and education corrected older adult normative data for a short form version of the Financial Capacity Instrument.
Financial capacity is an instrumental activity of daily living (IADL) that comprises multiple abilities and is critical to independence and autonomy in older adults. Because of its cognitive complexity, financial capacity is often the first IADL to show decline in prodromal and clinical Alzheimer's disease and related disorders. Despite its importance, few standardized assessment measures of financial capacity exist and there is little, if any, normative data available to evaluate financial skills in the elderly. The Financial Capacity Instrument-Short Form (FCI-SF) is a brief measure of financial skills designed to evaluate financial skills in older adults with cognitive impairment. In the current study, we present age- and education-adjusted normative data for FCI-SF variables in a sample of 1344 cognitively normal, community-dwelling older adults participating in the Mayo Clinic Study of Aging (MCSA) in Olmsted County, Minnesota. Individual FCI-SF raw scores were first converted to age-corrected scaled scores based on position within a cumulative frequency distribution and then grouped within 4 empirically supported and overlapping age ranges. These age-corrected scaled scores were then converted to age- and education-corrected scaled scores using the same methodology. This study has the potential to substantially enhance financial capacity evaluations of older adults through the introduction of age- and education-corrected normative data for the FCI-SF by allowing clinicians to: (a) compare an individual's performance to that of a sample of similar age and education peers, (b) interpret various aspects of financial capacity relative to a normative sample, and (c) make comparisons between these aspects. (PsycINFO Database Record


[Cardiac arrest in a teenager - a case report].
Cardiac arrest is rarely seen in children and teenagers. We present a 12-year old girl with cardiac arrest following myocardial infarction, that required prolonged cardiac massage and extracorporeal-membranous-oxygenation (ECMO). At coronary angiography the left main coronary artery (LMCA) was stented for a suspected coronary dissection. The contraction of the heart improved and the ECMO-treatment was discontinued a week later. The patient was discharged home, but six months later a coronary artery bypass surgery was performed for in-stent restenosis. Further work-up with computed tomography (CT) showed that the LMCA originated from the right aortic sinus instead of the the left one. This case demonstrates how life threatening myocardial infarction can be caused by coronary artery anomalies.


[Uracil in DNA--friend or foe?].
Uracil may arise in DNA, in small quantities as a result of spontaneous cytosine deamination or/and misincorporation of dUMP during DNA replication. However, just recently uracil formation via enzymatic deamiantion of cytosine, has been found to underlies diversification of Ig genes and inhibition of retroviral infection. DNA deamination is the only known programme in mammalian development in which the coding capacity of the genome is changed by targeted modification of deoxycitidine. In this paper we will review: i/sources of the origin of uracil in DNA, ii/the function of activation induced cytidine deaminase (AID) the enzyme which is responsible for cytidine deamination in Ig genes of B cell clones iii/some properties of the enzymes responsible for the excision of uracil. The role of uracil and above mentioned enzymes in Ig diversification process, which comprises somatic hypermutation and class switch recombination will also be discussed. Finally, we will discuss possible involvement of aberrantly expressed AID and presence of uracil in DNA, in carcinogenesis.


The adjuvant effect of peritoneal fluid in experimental peritonitis. Mechanism and clinical implications.
At laparotomy, many surgeons routinely instill crystalloid solutions into the peritoneal cavity, presumably to dilute out necrotic debris, bacteria, and adjuvant substances which foster bacterial growth. We examined the effect on mortality, bacterial growth, clearance, and phagocytosis of various volumes of saline instilled into the peritoneal cavity of rats during Escherichia coli peritonitis. Minimal intraperitoneal bacterial growth was seen after the introduction of a nonlethal inoculum of viable E. coli in 1 ml of saline, while administration of an identical inoculum in 30 ml of saline intraperitoneally (i.p.) led to increased 48-hour mortality (p less than 0.01), and associated rapid bacterial proliferation (p less than 0.01). Clearance of nonviable radiolabelled E. coli from the peritoneal cavity was delayed, bacterial association with host peritoneal leukocytes was decreased, and blood uptake of radiolabelled bacteria was diminished in animals receiving 30 ml of saline i.p., compared to controls which received the identical inoculum in 1 ml of saline i.p. The clinical relevance of these studies is manifold: (1) they provide a possible explanation why patients with ascites due to cirrhosis or the nephrotic syndrome, or those patients undergoing peritoneal dialysis are more susceptible to primary and secondary bacterial peritonitis, possibly on the basis of impaired peritoneal clearance or diminished phagocytosis and, (2) although irrigation of the peritoneal cavity with crystalloid solution would seem prudent during laparotomy, these solutions must be removed prior to closure to prevent interference with normal peritoneal host defense mechanisms.


Computed determination of the in vitro optimal chemocombinations of sphaeropsidin A with chemotherapeutic agents to combat melanomas.
Evasion to new treatments of advanced melanoma is still associated with a poor prognosis. Choosing the best combination of agents that can bypass resistance mechanisms remains a challenge. Sphaeropsidin A (Sph A) is a fungal bioactive secondary metabolite previously shown to force melanoma cells to undergo apoptosis via cell volume dysregulation. This work studied its in vitro combination with cytotoxic chemotherapeutics in a rational manner. Four melanoma cell lines harboring different sensitivity levels to pro-apoptotic stimuli were used to build a predictive response surface model allowing the determination of the optimal in vitro combinations of Sph A with two drugs, i.e., cisplatin or temozolomide, owing to a limited set of experimentations. Testing 12 experimental combinations allowed us to build an accurate predictive model that considers the complexity of the drug interaction and determines the optimal combinations according to the endpoint chosen, i.e., the maximal cytotoxic effects. Therefore, combining 4 µM Sph A with 75 µM cisplatin concomitantly for 72 h improved its cytotoxic effects on melanoma cells in a synergistic manner. An optimal in vitro treatment schedule was also obtained for temozolomide. The use of a response surface model offers the possibility of reducing the experiments while determining accurately the optimal combinations. We herein highlighted that combining the Na+/K+/2Cl- cotransporter and/or anion exchanger inhibitor Sph A with chemotherapeutic agents could improve the therapeutic benefits of conventional chemotherapies against advanced melanomas, particularly because Sph A exerts cytotoxic effects regardless of the genetic BRAF and NRAS status.


[Nodular forms of goiter as a cause of cancer of the thyroid gland].
The experience with diagnosis and treatment of struma maligna in 267 (5.5%) of the 4876 patients operated on for nodular forms of goiter is summarized. In the diagnosis, the puncture biopsy was widely used. Extrafascial resection of the thyroid gland with subsequent replacement therapy with thyroidin is a method of choice.


Self-care competence in the administration of insulin in older people aged 70 or over1.
to analyze the self-care competence in the administration of insulin performed by older people aged 70 or over. cross-sectional study carried out with 148 older people aged 70 or over, who performed self-administration of insulin. Data collection was carried out using a structured questionnaire and an adapted guide for the application of the Scale to Identify Self-Care Competence of Patients with Diabetes, at the participants' home. Data analysis included descriptive and inferential statistical tests, with forward logistic regression. the prevalence of self-care competence in the administration of insulin was 35.1%. Handwashing error was the most frequent in self-administration of insulin. Self-care competence was negatively associated with retirees and positively associated with senior patients who performed capillary blood glucose monitoring and skin pinching during insulin application. there was low self-care competence and it was associated with both the sociodemographic and the clinical characteristics with regard to self-application of insulin by the older people.


Returning the chronically unemployed with low back pain to employment.
Much of the research into return to work following rehabilitation for low back pain in the literature reflects work done in those employed. Unemployment is a consequence of chronic low back pain which has considerable health and economic consequences for the individual and society. This paper describes an occupationally orientated rehabilitation programme for long-term unemployed people (mean duration of unemployment 38.9 months). The aim of the project was to identify factors which predict return to work and progress towards employment. Eight six subjects underwent a pain management rehabilitation programme incorporating vocational focussing and advice, subjects were followed up at 6 months to determine work status. At follow-up 38.4% of subjects were employed and another 23% were in voluntary work, or education/training. There were no significant differences on presenting characteristics between those who returned to work and those who did not. Subjects were divided into those who made positive progress (work, education/training or voluntary work) and those who did not (remained unemployed, dropped out of the programme or lost to follow up). Those who failed to make positive progress were characterised by longer duration of unemployment and higher scores on somatic anxiety and depression. A predictive model was able to identify 80% of those who failed to make progress but prediction of those achieving a positive outcome was poor (44% correct prediction). The factors predicting return to work in unemployed people with low back pain differs from the employed, the need for employment skills training and a vocational focus to rehabilitation are highlighted.


Phosphate Starvation by Energy Metabolism Disturbance in Candida albicansvip1Δ/Δ Induces Lipid Droplet Accumulation and Cell Membrane Damage.
Phosphorus in the form of phosphate (Pi) is an essential element for metabolic processes, including lipid metabolism. In yeast, the inositol polyphosphate kinase vip1 mediated synthesis of inositol heptakisphosphate (IP7) regulates the phosphate-responsive (PHO) signaling pathway, which plays an important role in response to Pi stress. The role of vip1 in Pi stress and lipid metabolism of Candida albicans has not yet been studied. We found that when vip1Δ/Δ was grown in glucose medium, if Pi was supplemented in the medium or mitochondrial Pi transporter was overexpressed in the strain, the lipid droplet (LD) content was reduced and membrane damage was alleviated. However, further studies showed that neither the addition of Pi nor the overexpression of the Pi transporter affected the energy balance of vip1Δ/Δ. In addition, the LD content of vip1Δ/Δ grown in Pi limitation medium PNMC was lower than that grown in SC, and the metabolic activity of vip1Δ/Δ grown in PNMC was also lower than that grown in SC medium. This suggests that the increase in Pi demand by a high energy metabolic rate is the cause of LD accumulation in vip1Δ/Δ. In addition, in the vip1Δ/Δ strains, the core transcription factor PHO4 in the PHO pathway was transported to the vacuole and degraded, which reduced the pathway activity. However, this does not mean that knocking out vip1 completely blocks the activation of the PHO pathway, because the LD content of vip1Δ/Δ grown in the medium with β-glycerol phosphate as the Pi source was significantly reduced. In summary, the increased Pi demand and the decreased PHO pathway activity in vip1Δ/Δ ultimately lead to LD accumulation and cell membrane damage.


Portable paper sensors for the detection of heavy metals based on light transmission-improved quantification of colorimetric assays.
An accurate quantification method with a wide linearity range is paramount for the development of low-cost, portable and point-of-care sensors. This work reports a new approach to analyze the colorimetric assays on paper-based sensors using the quantification from a light transmission method. Compared to the commonly-developed color intensity measurement on scanned digital images, a portable transmission densitometer is capable of directly quantifying the optical density of colorimetric results. The detection of heavy metals in an aqueous system, including Fe(ii), Cu(ii), and Ni(ii), was carried out to demonstrate the good performance and reliability of this method. Our measurements show that the linear quantification range spans from 0.5-500 mg L-1 for the assays of Cu(ii) and Fe(ii) and from 2-500 mg L-1 for Ni(ii) based on the reading of transmitted light through the assay spot. As a comparison, the linear range is restricted to 0.5-50 mg L-1 for the same assays when analysed by the common reflection method, suggesting a significant improvement in the accuracy and sensitivity of high analyte concentrations from the light transmission method. By expanding the linearity range, this method further streamlines the sampling procedure during analysis and will greatly advance the future development of paper-based analytical sensors.


An RNAi screen for Aire cofactors reveals a role for Hnrnpl in polymerase release and Aire-activated ectopic transcription.
Aire induces the expression of a large set of autoantigen genes in the thymus, driving immunological tolerance in maturing T cells. To determine the full spectrum of molecular mechanisms underlying the Aire transactivation function, we screened an AIRE-dependent gene-expression system with a genome-scale lentiviral shRNA library, targeting factors associated with chromatin architecture/function, transcription, and mRNA processing. Fifty-one functional allies were identified, with a preponderance of factors that impact transcriptional elongation compared with initiation, in particular members of the positive transcription elongation factor b (P-TEFb) involved in the release of "paused" RNA polymerases (CCNT2 and HEXIM1); mRNA processing and polyadenylation factors were also highlighted (HNRNPL/F, SFRS1, SFRS3, and CLP1). Aire's functional allies were validated on transfected and endogenous target genes, including the generation of lentigenic knockdown (KD) mice. We uncovered the effect of the splicing factor Hnrnpl on Aire-induced transcription. Transcripts sensitive to the P-TEFb inhibitor flavopiridol were reduced by Hnrnpl knockdown in thymic epithelial cells, independently of their dependence on Aire, therefore indicating a general effect of Hnrnpl on RNA elongation. This conclusion was substantiated by demonstration of HNRNPL interactions with P-TEFb components (CDK9, CCNT2, HEXIM1, and the small 7SK RNA). Aire-containing complexes include 7SK RNA, the latter interaction disrupted by HNRNPL knockdown, suggesting that HNRNPL may partake in delivering inactive P-TEFb to Aire. Thus, these results indicate that mRNA processing factors cooperate with Aire to release stalled polymerases and to activate ectopic expression of autoantigen genes in the thymus.


HU-671, a Novel Oleoyl Serine Derivative, Exhibits Enhanced Efficacy in Reversing Ovariectomy-Induced Osteoporosis and Bone Marrow Adiposity.
Oleoyl serine (OS), an endogenous fatty acyl amide (FAA) found in bone, has been shown to have an anti-osteoporotic effect. OS, being an amide, can be hydrolyzed in the body by amidases. Hindering its amide bond by introducing adjacent substituents has been demonstrated as a successful method for prolonging its skeletal activity. Here, we tested the therapeutic efficacy of two methylated OS derivatives, oleoyl α-methyl serine (HU-671) and 2-methyl-oleoyl serine (HU-681), in an ovariectomized mouse model for osteoporosis by utilizing combined micro-computed tomography, histomorphometry, and cell culture analyses. Our findings indicate that daily treatment for 6 weeks with OS or HU-671 completely rescues bone loss, whereas HU-681 has only a partial effect. The increased bone density was primarily due to enhanced trabecular thickness and number. Moreover, the most effective dose of HU-671 was 0.5 mg/kg/day, an order of magnitude lower than with OS. The reversal of bone loss resulted from increased bone formation and decreased bone resorption, as well as reversal of bone marrow adiposity. These results were further confirmed by determining the serum levels of osteocalcin and type 1 collagen C-terminal crosslinks, as well as demonstrating the enhanced antiadipogenic effect of HU-671. Taken together, these data suggest that methylation interferes with OS's metabolism, thus enhancing its effects by extending its availability to its target cells.


Direct imaging of lithium atoms in LiV₂O₄ by spherical aberration-corrected electron microscopy.
We visualized lithium atom columns in LiV₂O₄ crystals by combining scanning transmission electron microscopy with annular bright field (ABF) imaging using a spherical aberration-corrected electron microscope (R005) viewed from the [110] direction. The incident electron beam was coherent with a convergent angle of 30 mrad (semi-angle), and the detector collected scattered electrons over 20-30 mrad (semi-angle). The ABF image showed dark dots corresponding to lithium, vanadium and oxygen columns.


A Variable State Dimension Approach to Meal Detection and Meal Size Estimation: In Silico Evaluation Through Basal-Bolus Insulin Therapy for Type 1 Diabetes.
This paper aims to develop an algorithm that can detect unannounced meals and estimate meal sizes to achieve a robust glucose control. A variable state dimension (VSD) algorithm is developed to detect unannounced meals and estimate meal sizes, where a Kalman filter operates on a quiescent state model when no meal is detected, and switches to a maneuvering state model to estimate meal information once the meal-induced glucose variability is statistically significant. Through evaluation using 30 subjects of the UVa/Padova simulator, a basal-bolus (BB) control using the VSD-estimated meal size for each meal can achieve mean blood glucose (BG) of 142 mg/dl with an average 17.7% of time in hypoglycemia. In terms of 20 Monte-Carlo simulations for each subject over a two-day scenario, where each meal/snack has a probability of 0.5 not to be announced, the BB control using VSD for unannounced meals can achieve an average mean BG of 143 mg/dl with 8% of time in hypoglycemia, in contrast to mean BG of 180 mg/dl with 8% of time in hypoglycemia obtained by BB with missing boluses. Additionally, VSD is able to detect a meal within 45 (±14) min since its start with a 76% success rate and 16% false alarm rate. The addition of VSD to the BB control improves glucose control when meal announcements are missed. The VSD can be used as a complementary tool to detect meal and estimate meal size in absence of a meal announcement.


Social determinants of male partner attendance in women's prevention-of mother-to-child transmission program in Malawi.
Male partners are rarely present during PMTCT (Prevention-Mother-To-Child-Transmission) services in Sub-Saharan Africa (SSA). Male involvement is increasingly recognised as an important element of women's access to care. This study aims to identify the socio-demographic characteristics, HIV-Knowledge, Attitude and Practice (KAP) among women accompanied and not accompanied by their male partners. We included pregnant women enrolled in PMTCT programme between August 2018 and November 2019 in the Southern Region of Malawi. Eligible women were aged 18 years or older, living with a male partner, enrolled for the first time in one of the four selected facilities. We provided a KAP survey to women and their partners attending the facilities. Our primary objective was to assess and analyse the proportion of women who were accompanied by their partner at least once. We applied descriptive statistics and logistic regressions to study the association between being accompanied and explanatory variables. We enrolled 128 HIV-positive women: 82 (64.1%) were accompanied by their male partners and 46 (35.9%) were alone. In the multivariable model, women's unemployment and owning a means of transport are negatively associated with male attendance (respectively adjusted OR 0.32 [95% CI, 0.11-0.82] and 0.23 [95% CI, 0.07-0.77]), whereas, in the univariable model, high women's level of knowledge of HIV is positively associated with male attendance (OR 2.17 [95% CI, 1.03-4.58]). Level of attitude and practice toward HIV were not significantly associated to our study variable. Our study shows a high male attendance in Malawi compared to other studies performed in SSA. This study highlights that women's level of knowledge on HIV and their economic condition (employment and owning a means of transport) affects male attendance. Moreover, the study points out that gender power relationships and stringent gender norms play a crucial role thus they should be considered to enhance male involvement.


Scalp dermatoscopic findings in androgenetic alopecia and their relations with disease severity.
Clinicians are searching for new methods to diagnose and predict the course of androgenetic alopecia noninvasively. Our aim is to evaluate trichoscopic findings and their relations with disease severity in androgenetic alopecia. The videodermatoscopic findings of 143 female and 63 male patients with androgenetic alopecia were compared with each other, with those of healthy subjects (n=100), and with those of patients with other nonscarring alopecias (n=208). Mann-Whitney U-test, χ(2) analyses, and logistic regression analysis were used for statistical analysis. No statistically significant relation was found between trichoscopic findings and severity in male androgenetic alopecia (MAGA) on the basis of the modified Hamilton Norwood scale (among 7 degrees); however, multihair follicular unit and perifollicular pigmentation were related to low severity whereas white dots, honeycomb pattern pigmentation, and brown dots were related to high severity. On the other hand, according to the Ludwig classification, arborizing red lines were related to low severity and brown dots were related to high severity, whereas there was no difference in stages between the Ebling and Olsen classifications in female androgenetic alopecia (FAGA). In the characteristic trichoscopic findings in this study, perifollicular pigmentation was found as a normal feature of the scalp, whereas multihair follicular unit and honeycomb pigment pattern, which were previously considered as normal features, were observed to be related to androgenetic alopecia. No relation was found between MAGA severity and trichoscopic findings, as well as between FAGA severity according to different disease severity classifications and trichoscopic findings.


Patients with negative patch tests: Retrospective analysis of North American Contact Dermatitis Group (NACDG) data 2001-2016.
Little is known regarding the characteristics of patients with negative patch test (NPT) results. To characterize patients with NPT results. Retrospective cross-sectional analysis of 34,822 patch tested patients. NPT results were defined as negative or irritant final interpretations of all North American Contact Dermatitis Group screening allergens and no relevant allergens on supplemental series. Almost one-third of patients (n = 10,888 [31.3%]) had NPT results. Patients with NPT results were significantly more likely to be male (P < .0001), be age 40 years or younger (P = .0054), be nonwhite (P = .0005), and have dermatitis primarily having a scattered generalized distribution (P = .0007) or primarily located on the lips (P = .0214) or eyelids (P = .0364). However, the absolute differences in age, race, and site were small and may not be clinically meaningful. Patients with NPT results were significantly less likely to have occupationally related skin disease (P < .0001). Overall, 8.3% of patients with NPT results had occupationally related skin disease, with precision production worker/machine operator (28.5%), health care worker (17.0%), and mechanic/repairer (7.5%) being the most commonly related occupations. In all, 22.9% of patients with NPT results had relevant irritants and 41.6% of irritants were occupationally related; cosmetics/health care products and soaps were common sources for both occupationally related and non-occupationally related irritants. Retrospective cross-sectional study of tertiary referral population. Patients with NPT results have distinct characteristics.


Factors influencing oncology nurses' approaches to accommodating cultural needs in palliative care.
The purpose of this study is to explore the social construction of cultural issues in palliative care amongst oncology nurses. Australia is a nation composed of people from different cultural origins with diverse linguistic, spiritual, religious and social backgrounds. The challenge of working with an increasingly culturally diverse population is a common theme expressed by many healthcare professionals from a variety of countries. Grounded theory was used to investigate the processes by which nurses provide nursing care to cancer patients from diverse cultural backgrounds. Semi-structured interviews with seven Australian oncology nurses provided the data for the study; the data was analysed using grounded theory data analysis techniques. The core category emerging from the study was that of accommodating cultural needs. This paper focuses on describing the series of subcategories that were identified as factors which could influence the process by which nurses would accommodate cultural needs. These factors included nurses' views and understandings of culture and cultural mores, their philosophy of cultural care, nurses' previous experiences with people from other cultures and organisational approaches to culture and cultural care. This study demonstrated that previous experiences with people from other cultures and organisational approaches to culture and cultural care often influenced nurses' views and understandings of culture and cultural mores and their beliefs, attitudes and behaviours in providing cultural care. Relevance to clinical practice. It is imperative to appreciate how nurses' experiences with people from other cultures can be recognised and built upon or, if necessary, challenged. Furthermore, nurses' cultural competence and experiences with people from other cultures need to be further investigated in clinical practice.


Mutation Spectrum of the ABCA4 Gene in 335 Stargardt Disease Patients From a Multicenter German Cohort-Impact of Selected Deep Intronic Variants and Common SNPs.
Stargardt disease (STGD1) is an autosomal recessive retinopathy, caused by mutations in the retina-specific ATP-binding cassette transporter (ABCA4) gene. To establish the mutational spectrum and to assess effects of selected deep intronic and common genetic variants on disease, we performed a comprehensive sequence analysis in a large cohort of German STGD1 patients. DNA samples of 335 STGD1 patients were analyzed for ABCA4 mutations in its 50 coding exons and adjacent intronic sequences by resequencing array technology or next generation sequencing (NGS). Parts of intron 30 and 36 were screened by Sanger chain-terminating dideoxynucleotide sequencing. An in vitro splicing assay was used to test selected variants for their splicing behavior. By logistic regression analysis we assessed the association of common ABCA4 alleles while a multivariate logistic regression model calculated a genetic risk score (GRS). Our analysis identified 148 pathogenic or likely pathogenic mutations, of which 48 constitute so far unpublished ABCA4-associated disease alleles. Four rare deep intronic variants were found once in 472 alleles analyzed. In addition, we identified six risk-modulating common variants. Genetic risk score estimates suggest that defined common ABCA4 variants influence disease risk in carriers of a single pathogenic ABCA4 allele. Our study adds to the mutational spectrum of the ABCA4 gene. Moreover, in our cohort, deep intronic variants in intron 30 and 36 likely play no or only a minor role in disease pathology. Of note, our findings demonstrate a possible modifying effect of common sequence variants on ABCA4-associated disease.


Effects of reestablishing blood flow on extent of myocardial infarction in conscious dogs.
The effects of permanent circumflex coronary artery occlusion (PO) compared with reestablishing blood flow (OR) at 2 and 6 h after occlusion on the final extent of histological infarction (HI) was assessed in chronically instrumented awake dogs. The relationships between the extent of left ventricular ischemia measured by microsphere techniques and HI in the PO group were used as models to predict the expected infarction in the 2- and 6-h OR groups. Mean HI (+/-SD) in the PO and 6- and 2-h OR groups was 21 +/- 13, 19 +/- 10, and 13 +/- 12% of left ventricular weight, respectively; values were not significantly different. The extent of HI in samples grouped according to epicardial and endocardial layers and ischemic blood flow ranges (0-15, 16-30, 31-50, 51-75% of control region blood flow) was reduced in the 2-h but not 6-h OR group. Analysis of individual animals using total ischemic region blood flow to epicardial and endocardial layers demonstrated that OR at 2 h but not 6 h reduced infarction in most animals but not in certain animals with the largest ischemic regions.


Toll-Like Receptor 4 and Heat-Shock Protein 70: Is it a New Target Pathway for Diabetic Vasculopathies?
Diabetes is one of the most concerning diseases in modern times. Despite considerable advances in therapeutic management, the prevalence of diabetes and its contribution to death and disability continue to be a major health problem. Diabetic vasculopathies are the leading cause of mortality and morbidity in diabetic patients. Its pathophysiology includes oxidative stress, advanced glycation end products, and a low-grade inflammatory state. Lately, actions of the innate immune system via Toll-like receptors (TLRs) have been suggested as a new insight in this field. TLRs are pattern recognition receptors activated by highly conserved structural motifs of exogenous or endogenous ligands. Heat-shock proteins (HSPs), normally known for their ability to protect cells during stressful conditions, when released from injured cells bind to TLR4 and trigger the release of pro-inflammatory cytokines in a MyD88-dependent pathway. This pathway had been investigated in pancreatic beta cells and skeletal muscle, but it has not yet been explored in the vascular system and deserves investigation. In this work, the interplay between TLR4 and HSP70 in the vasculature during diabetes is reviewed and discussed. The current literature and preliminary results from our laboratory led us to hypothesize that hyperglycemia-associated HSP70 plays an important role in the pathophysiology of diabetic vasculopathies via the TLR4 pathway and might be a new target for therapeutic intervention.


[Questions on the efficiency of membrane technology in treating periodontal diseases. Experience of experimental and clinical studies].
Experimental and morphological studies demonstrated that Gore Resolute resorbable membrane can cause local inflammatory reactions similar to allergic. Collagen-based biomembranes coated with hydroxyapatite cause no local pathological reactions, but are rapidly resorbed in foci of degeneration under the effect of aggressive factors of tissue environment. Russian silicone membrane has been clinically tried with satisfactory results in patients with generalized periodontitis; the results prompt further studies of the membrane.


Adaptive rate-distortion optimal in-loop quantization for matching pursuit.
In this paper, an adaptive in-loop quantization technique is proposed for quantizing inner product coefficients in matching pursuit. For each matching pursuit (MP) stage a different quantizer is used based on the probability distribution of MP coefficients. The quantizers are optimized for a given rate budget constraint. Additionally, our proposed adaptive quantization scheme finds the optimal quantizers for each stage based on the already encoded inner product coefficients. Experimental results show that our proposed adaptive quantization scheme outperforms existing quantization methods used in matching pursuit image coding.


Effects of Stereoscopic Depth on Vigilance Performance and Cerebral Hemodynamics.
We tested the possibility that monitoring a display wherein critical signals for detection were defined by a stereoscopic three-dimensional (3-D) image might be more resistant to the vigilance decrement, and to temporal declines in cerebral blood flow velocity (CBFV), than monitoring a display featuring a customary two-dimensional (2-D) image. Hancock has asserted that vigilance studies typically employ stimuli for detection that do not exemplify those that occur in the natural world. As a result, human performance is suboptimal. From this perspective, tasks that better approximate perception in natural environments should enhance performance efficiency. To test that possibility, we made use of stereopsis, an important means by which observers interact with their everyday surroundings. Observers monitored a circular display in which a vertical line was embedded. Critical signals for detection in a 2-D condition were instances in which the line was rotated clockwise from vertical. In a 3-D condition, critical signals were cases in which the line appeared to move outward toward the observer. The overall level of signal detection and the stability of detection over time were greater when observers monitored for 3-D changes in target depth compared to 2-D changes in target orientation. However, the 3-D display did not retard the temporal decline in CBFV. These results provide the initial demonstration that 3-D displays can enhance performance in vigilance tasks. The use of 3-D displays may be productive in augmenting system reliability when operator vigilance is vital.


How I do it: Cone-beam CT during transarterial chemoembolization for liver cancer.
Cone-beam computed tomography (CBCT) is an imaging technique that provides computed tomographic (CT) images from a rotational scan acquired with a C-arm equipped with a flat panel detector. Utilizing CBCT images during interventional procedures bridges the gap between the world of diagnostic imaging (typically three-dimensional imaging but performed separately from the procedure) and that of interventional radiology (typically two-dimensional imaging). CBCT is capable of providing more information than standard two-dimensional angiography in localizing and/or visualizing liver tumors ("seeing" the tumor) and targeting tumors though precise microcatheter placement in close proximity to the tumors ("reaching" the tumor). It can also be useful in evaluating treatment success at the time of procedure ("assessing" treatment success). CBCT technology is rapidly evolving along with the development of various contrast material injection protocols and multiphasic CBCT techniques. The purpose of this article is to provide a review of the principles of CBCT imaging, including purpose and clinical evidence of the different techniques, and to introduce a decision-making algorithm as a guide for the routine utilization of CBCT during transarterial chemoembolization of liver cancer.


Social recovery and the move beyond deficit models of depression: a feminist analysis of mid-life women's self-care practices.
In Australia, like other advanced liberal democracies, the adoption of a recovery orientation was hailed as a major leap forward in mental health policy and service provision. We argue that this shift in thinking about the meaning of recovery requires further analysis of the gendered dimension of self-identity and relationships with the social world. In this article we focus on how mid-life women constructed meaning about recovery through their everyday practices of self-care within the gendered context of depression. Findings from our qualitative research with 31 mid-life women identified how the recovery process was complicated by relapses into depression, with many women critically questioning the limitations of biomedical treatment options for a more relational understanding of recovery. Participant stories revealed important tacit knowledge about recovery that emphasised the process of realising and recognising capacities and self-knowledge. We identify two central themes through which women's tacit knowledge of this changing relation to self in recovery is made explicit: the disciplined self of normalised recovery, redefining recovery and depression. The findings point to the need to reconsider how both recovery discourses and gendered expectations can complicate women's experiences of moving through depression. We argue for a different conceptualisation of recovery as a social practice through which women realise opportunities to embody different 'beings and doings'. A gendered understanding of what women themselves identify is important to their well-being, can contribute to more effective recovery oriented policies based on capability rather than deficit.


Development of a reliable extraction and quantification method for glucosinolates in Moringa oleifera.
Glucosinolates are the characteristic secondary metabolites of plants in the order Brassicales. To date the common DIN extraction 'desulfo glucosinolates' method remains the common procedure for determination and quantification of glucosinolates. However, the desulfation step in the extraction of glucosinolates from Moringa oleifera leaves resulted in complete conversion and degradation of the naturally occurring glucosinolates in this plant. Therefore, a method for extraction of intact Moringa glucosinolates was developed and no conversion and degradation of the different rhamnopyranosyloxy-benzyl glucosinolates was found. Buffered eluents (0.1 M ammonium acetate) were necessary to stabilize 4-α-rhamnopyranosyloxy-benzyl glucosinolate (Rhamno-Benzyl-GS) and acetyl-4-α-rhamnopyranosyloxy-benzyl glucosinolate isomers (Ac-Isomers-GS) during HPLC analysis. Due to the instability of intact Moringa glucosinolates at room temperature and during the purification process of single glucosinolates, influences of different storage (room temperature, frozen, thawing and refreezing) and buffer conditions on glucosinolate conversion were analysed. Conversion and degradations processes were especially determined for the Ac-Isomers-GS III.


Hepatic angiomyolipoma associated with splenic hamartoma.
A 52-year-old woman was admitted to our hospital with thrombophlebitis of the internal jugular vein. Abdominal ultrasonography demonstrated a high echogenic mass measuring 4.5 cm in diameter in the liver, and abdominal CT revealed another liver tumor and an isodensity mass in the spleen. Abdominal MRI and angiography were performed and we presumed the tumors to be two hepatic angiomyolipoma and a splenic hamartoma. As an abdominal CT 21 months later revealed that all tumors were growing, these tomors were surgically resected. The histological diagnoses were hepatic angiomyolipoma and splenic hamartoma.


RamA is an alternate activator of the multidrug resistance cascade in Enterobacter aerogenes.
Multidrug resistance (MDR) in Enterobacter aerogenes can be mediated by induction of MarA, which is triggered by certain antibiotics and phenolic compounds. In this study, we identified the gene encoding RamA, a 113-amino-acid regulatory protein belonging to the AraC-XylS transcriptional activator family, in the Enterobacter aerogenes ATCC 13048 type strain and in a clinical multiresistant isolate. Overexpression of RamA induced an MDR phenotype in drug-susceptible Escherichia coli JM109 and E. aerogenes ATCC 13048, as demonstrated by 2- to 16-fold-increased resistance to beta-lactams, tetracycline, chloramphenicol, and quinolones, a decrease in porin production, and increased production of AcrA, a component of the AcrAB-TolC drug efflux pump. We show that RamA enhances the transcription of the marRAB operon but is also able to induce an MDR phenotype in a mar-deleted strain. We demonstrate here that RamA is a transcriptional activator of the Mar regulon and is also a self-governing activator of the MDR cascade.


Successful Conversion Surgery for Advanced Gastric Cancer With Multiple Liver Metastases Following Ramucirumab Plus Paclitaxel Combination Treatment.
To present the case of a patient with unresectable gastric cancer showing a remarkable effect by second-line drug treatment with ramucirumab plus paclitaxel and conversion surgery. A 68-year-old woman who was diagnosed with gastric cancer was referred to us. Esophagogastroduodenoscopy showed an ulcerated lesion with an irregular nodulated border in the lower third of the stomach, and histology of biopsied specimens indicated a poorly differentiated adenocarcinoma. Enhanced computed tomography revealed extensive invasion of the liver, and the patients was treated using S-1 plus oxaliplatin as first-line chemotherapy. Because she developed liver metastases, the treatment regimen was changed to ramucirumab plus paclitaxel as the second-line treatment. After four cycles of weekly paclitaxel with ramucirumab treatment, the liver metastases had completely disappeared. Because no other metastatic lesions in other organs were detected, we performed total gastrectomy with D2 lymphadenectomy. The macroscopic findings of the surgically resected specimen revealed an ulcerated lesion with an irregularly modulated lesion measuring 9.5×4.5 cm. Pathological analysis demonstrated a poorly differentiated adenocarcinoma in the stomach, with invasion to the liver through the serosal layer, and seven lymph node metastases. The postoperative course was unremarkable, and she received ramucirumab in combination with paclitaxel treatment. However, liver metastasis appeared at 4 months after the operation, for which she was treated with irinotecan. Although the patient continued to receive irinotecan chemotherapy for 10 months, her general condition gradually deteriorated, and she was started on best supportive care 13 months after conversion surgery. Conversion surgery may prolong survival not only through first-line but also second-line treatments in selected patients with unresectable advanced gastric cancer; however, assessments of additional cases and further studies are required to establish this treatment strategy.


Neural signatures of dynamic emotion constructs in the human brain.
How is emotion represented in the brain: is it categorical or along dimensions? In the present study, we applied multivariate pattern analysis (MVPA) to magnetoencephalography (MEG) to study the brain's temporally unfolding representations of different emotion constructs. First, participants rated 525 images on the dimensions of valence and arousal and by intensity of discrete emotion categories (happiness, sadness, fear, disgust, and sadness). Thirteen new participants then viewed subsets of these images within an MEG scanner. We used Representational Similarity Analysis (RSA) to compare behavioral ratings to the unfolding neural representation of the stimuli in the brain. Ratings of valence and arousal explained significant proportions of the MEG data, even after corrections for low-level image properties. Additionally, behavioral ratings of the discrete emotions fear, disgust, and happiness significantly predicted early neural representations, whereas rating models of anger and sadness did not. Different emotion constructs also showed unique temporal signatures. Fear and disgust - both highly arousing and negative - were rapidly discriminated by the brain, but disgust was represented for an extended period of time relative to fear. Overall, our findings suggest that 1) dimensions of valence and arousal are quickly represented by the brain, as are some discrete emotions, and 2) different emotion constructs exhibit unique temporal dynamics. We discuss implications of these findings for theoretical understanding of emotion and for the interplay of discrete and dimensional aspects of emotional experience.


Experimental investigation of transverse mixing in porous media under helical flow conditions.
Plume dilution and transverse mixing can be considerably enhanced by helical flow occurring in three-dimensional heterogeneous anisotropic porous media. In this study, we perform tracer experiments in a fully three-dimensional flow-through chamber to investigate the effects of helical flow on plume spiraling and deformation, as well as on its dilution. Porous media were packed in angled stripes of materials with different grain sizes to create blocks with macroscopically anisotropic hydraulic conductivity, which caused helical flows. Steady-state transport experiments were carried out by continuously injecting dye tracers at different inlet ports. High-resolution measurements of concentration and flow rates were performed at 49 outlet ports. These measurements allowed quantifying the spreading and dilution of the solute plumes at the outlet cross section. Direct evidence of plume spiraling and visual proof of helical flow was obtained by freezing and slicing the porous media at different cross sections and observing the dye-tracer distribution. We simulated flow and transport to interpret our experimental observations and investigate the effects of helical flow on mixing-controlled reactive transport. The simulation results were evaluated using metrics of reactive mixing such as the critical dilution index and the length of continuously injected steady-state plumes. The results show considerable reaction enhancement, quantified by the remarkable decrease of reactive plume lengths (up to four times) in helical flows compared to analogous scenarios in uniform flows.


HER2 expression in salivary gland carcinomas: dependence on histological subtype.
Previous evaluation of HER2 overexpression in salivary gland cancers indicated an incidence varying between 7 and 56%, with no clear difference among three histologically different subtypes. As part of a Phase II trial of trastuzumab for treatment of incurable salivary gland cancer, we screened 137 tumors for HER2 expression. Unstained sections of paraffin-embedded tumor samples were stained with p185/HER2 receptor antibody. Tumors with moderate (2+) to strong (3+) complete membrane staining in at least 10% of the tumor cells were scored as positive for overexpression. The overall frequency of overexpression for HER2 was 17% (23 of 137), whereas it was only 8% in the three most common histological subtypes screened. Overexpression was distinctly rare in the most common subtype screened, adenoid cystic carcinoma (4%, 3 of 70). Overexpression was very common in salivary duct cancers; 10 (83%) of 12 were positive for HER2. This observation is consistent with the typical high-grade histological features and aggressive behavior of this subtype as well as with its histogenetic similarity to breast cancer. Analysis based on histogenesis (intercalated duct versus excretory duct) indicated a higher frequency of overexpression in the latter (55%) than in the former (7%). Our overall results suggest that trastuzumab will not have a major role in treatment of salivary gland cancers of intercalated duct origin. Further systematic evaluation of trastuzumab in subtypes of excretory duct origin could be supported.


Inactivation of salmonella in biofilms and on chicken cages and preharvest poultry by levulinic Acid and sodium dodecyl sulfate.
Surface contamination (skin and feathers) of broilers with Salmonella occurs primarily during growth and transportation. Immediately after transporting chickens, chicken cage doors were sprayed with a foam containing 3% levulinic acid plus 2% sodium dodecyl sulfate (SDS). Samples were collected for Salmonella assay after 45 min. Salmonella on cage doors was reduced from 19% (19 of 100 doors) before treatment to 1% (1 of 100 doors) after treatment, coliform counts were reduced from 6 to 8 to 2 to 4 log CFU/9 cm(2), and aerobic plate counts were reduced from 7 to 9 to 4 to 6 log CFU/9 cm(2). Whole chicken carcasses with feathers were inoculated with 10(8) CFU of Salmonella Enteritidis, soaked for 5 min at 21°C in 72 liters of a treatment or control solution, and assayed for Salmonella. Salmonella counts on chickens treated with water were 6.8 to 8.5 log CFU/9 cm(2), those treated with 50 ppm of calcium hypochlorite were 7.6 to 8.9 log CFU/9 cm(2), and those treated with 3% levulinic acid plus 2% SDS were <1.7 to 2.8 CFU/9 cm(2) (>4-log reduction). Results of biofilm studies on surfaces of various materials revealed that a 3% levulinic acid plus 2% SDS treatment used as either a foam or liquid for 10 min effectively reduced Salmonella populations by 5 and >6 log CFU/cm(2), respectively.


Chondroitin sulfate mediates liver responses to injury induced by dual endothelin receptor inhibition.
Although dual endothelin receptor antagonists (ERAs) show great promise for treating various conditions, their propensity to induce liver injury limits their clinical usage. Inflammation and fibrosis are important processes in liver responses to injury and it has been suggested that they and dual ERA-induced liver injury are mediated by the proteoglycan component chondroitin sulfate (CS), which is synthesized by CHST3 and CHST13. In this study, we investigated whether dual ER inhibition in the liver could alter CHST3 and CHST13 expression and thus CS production and whether liver CS content could prevent inflammatory and fibrosis responses after liver injury. We observed increased CHST3 and CHST13 expression after liver injury in bile duct ligated mice and histologically confirmed abundant CS deposition in the injured liver. Moreover, treating Hep3B cells with a dual ERA mimic significantly increased CHST3 and CHST13 expression, inflammatory cytokine levels, and glycosaminoglycan deposition. Furthermore, pro-inflammatory and pro-fibrotic markers were observed after dual ERA treatment, while treatment with CS-degrading chondroitinase ABC was able to successfully reverse these phenotypes. These observations suggest that CHST3- and CHST13-induced CS production can mediate liver injury responses caused by dual ER inhibition and thus could be an alternative pathway for treating ERA-induced liver injury.


Calcium Signaling Is Required for Erythroid Enucleation.
Although erythroid enucleation, the property of erythroblasts to expel their nucleus, has been known for 7ore than a century, surprisingly little is known regarding the molecular mechanisms governing this unique developmental process. Here we show that similar to cytokinesis, nuclear extrusion requires intracellular calcium signaling and signal transduction through the calmodulin (CaM) pathway. However, in contrast to cytokinesis we found that orthochromatic erythroblasts require uptake of extracellular calcium to enucleate. Together these functional studies highlight a critical role for calcium signaling in the regulation of erythroid enucleation.


Perceptions of partner's deception in friends with benefits relationships.
Friends-with-benefits relationships combine elements of friendship with sexual intimacy. Using hierarchical regression, the authors examined perceived deception in 310 relationships. In comparison with men, women reported greater deception by their friends-with-benefits partner. Perceived deception was inversely related to awareness of relational risk factors and directly related to anxious attachment, more sexual interactions as compared with friendship interactions in the relationship, and more favorable attitudes toward ambiguous commitment. Awareness of relational risk factors moderated the association between anxious attachment and perceptions of being deceived as awareness of relational risk factors was only negatively associated with perceived deception for those with lower levels of anxious attachment. Last, gender moderated the association between perceptions of being deceived and anxious attachment in that more anxious attachment was related to perceived deception for women, but not men. In particular, anxious attachment did not predict perceptions of deception for men, but greater degrees of anxious attachment for women increased perceptions of deception. Recommendations for assisting young adults to navigate this relational style are offered.


Properties of Haemophilus influenzae mutants that are slightly recombination deficient and carry a mutation in the rec-1 gene region.
The highly recombination-deficient rec-1 mutants of Haemophilus influenzae are, as far as tested, equivalent to recA mutants of Escherichia coli. By selection for mutations in the rec-1 gene of H. influenzae, mutants designated ird (intermediary recombination-deficient) mutants were isolated; these mutants were much less recombination deficient (degree of transformability, 0.2 to 30% of wild-type value) than previously isolated rec-1 mutants (degree of transformability, 0.0001% of wild-type value). The ird mutants were more sensitive to ultraviolet irradiation and mytomycin C treatment than the wild type, but less sensitive than rec-1 mutants. Spontaneous production of phage HP1c1 by lysogenic MC11 cells and prophage induction by mitomycin C or ultraviolet irradiation were the same as in the wild type. In the ird mutants endogenous deoxyribonucleic acid was degraded both spontaneously and after ultraviolet irradiation to the same extent as in the wild type. Examination of one of the ird mutants revealed that recombination could be enhanced by ultraviolet irradiation, possibly because of an increased synthesis of the rec-1 gene product induced by ultraviolet irradiation.


Tuning the bandgap of Cs2AgBiBr6 through dilute tin alloying.
The promise of lead halide hybrid perovskites for optoelectronic applications makes finding less-toxic alternatives a priority. The double perovskite Cs2AgBiBr6 (1) represents one such alternative, offering long carrier lifetimes and greater stability under ambient conditions. However, the large and indirect 1.95 eV bandgap hinders its potential as a solar absorber. Here we report that alloying crystals of 1 with up to 1 atom% Sn results in a bandgap reduction of up to ca. 0.5 eV while maintaining low toxicity. Crystals can be alloyed with up to 1 atom% Sn and the predominant substitution pathway appears to be a ∼2 : 1 substitution of Sn2+ and Sn4+ for Ag+ and Bi3+, respectively, with Ag+ vacancies providing charge compensation. Spincoated films of 1 accommodate a higher Sn loading, up to 4 atom% Sn, where we see mostly Sn2+ substitution for both Ag+ and Bi3+. Density functional theory (DFT) calculations ascribe the bandgap redshift to the introduction of Sn impurity bands below the conduction band minimum of the host lattice. Using optical absorption spectroscopy, photothermal deflection spectroscopy, X-ray absorption spectroscopy, 119Sn NMR, redox titration, single-crystal and powder X-ray diffraction, multiple elemental analysis and imaging techniques, and DFT calculations, we provide a detailed analysis of the Sn content and oxidation state, dominant substitution sites, and charge-compensating defects in Sn-alloyed Cs2AgBiBr6 (1:Sn) crystals and films. An understanding of heterovalent alloying in halide double perovskites opens the door to a wider breadth of potential alloying agents for manipulating their band structures in a predictable manner.


Quality of life in Alzheimer disease: a comparison of patients' and caregivers' points of view.
Unlike in other chronic diseases, the Quality of Life (QoL) of patients affected by Alzheimer Disease (AD) has not been well established, primarily because of the difficulties stemming from the study of patients with cognitive disorders. Because no cure is currently available for AD, the optimization of QoL represents the best possible outcome attainable in all stages of disease, making QoL assessment mandatory. This study identified variables related to patients' QoL and examined the agreement between patients' and caregivers' QoL ratings. A total of 135 dyads (patient and principal caregiver) were enrolled in the study. Patients' QoL evaluations showed a negative relationship with depressive mood and a positive relationship with Activities of Daily Living (ADL), whereas caregivers' QoL ratings showed a negative relationship with patients' depressive mood and behavioral disturbances. Caregivers tended to underestimate patients' QoL compared with the patients' own self-evaluations, with patients' dependency in performing ADL and behavioral disorders as well as caregivers' burdens and depression being the main factors associated with the discrepancy in these evaluations. These findings suggest that the use of proxies as a substitute for the self-report of QoL data should be treated with caution, always accounting for the presence of potential bias.


Aminoglycoside 6'-N-acetyltransferase Type Ib [AAC(6')-Ib]-Mediated Aminoglycoside Resistance: Phenotypic Conversion to Susceptibility by Silver Ions.
Clinical resistance to amikacin and other aminoglycosides is usually due to the enzymatic acetylation of the antimicrobial molecule. A ubiquitous resistance enzyme among Gram-negatives is the aminoglycoside 6'-N-acetyltransferase type Ib [AAC(6')-Ib], which catalyzes acetylation using acetyl-CoA as a donor substrate. Therapies that combine the antibiotic and an inhibitor of the inactivation reaction could be an alternative to treat infections caused by resistant bacteria. We previously observed that metal ions such as Zn2+ or Cu2+ in complex with ionophores interfere with the AAC(6')-Ib-mediated inactivation of aminoglycosides and reduced resistance to susceptibility levels. Ag1+ recently attracted attention as a potentiator of aminoglycosides' action by mechanisms still in discussion. We found that silver acetate is also a robust inhibitor of the enzymatic acetylation mediated by AAC(6')-Ib in vitro. This action seems to be independent of other mechanisms, like increased production of reactive oxygen species and enhanced membrane permeability, proposed to explain the potentiation of the antibiotic effect by silver ions. The addition of this compound to aac(6')-Ib harboring Acinetobacter baumannii and Escherichia coli cultures resulted in a dramatic reduction of the resistance levels. Time-kill assays showed that the combination of silver acetate and amikacin was bactericidal and exhibited low cytotoxicity to HEK293 cells.


Effects of social interaction on well-being: development aspects.
The scientific need for nonhuman primates that are born and raised in captivity seems certain to increase and with it, the concern for managing the social development of individual animals so as to maximize their utility throughout a potentially long career. This practical objective is not only compatible with a concern for psychological well-being, but presupposes similar aims and criteria. For both concerns the most reliable guidelines are derived from basic research. The data available indicate that primate social development is directional, proceeding from extreme dependence on care-givers initially (subserved by mother-directed behaviors) toward relative autonomy and adult competence (dominated by other-directed behaviors). Individuals are not passive recipients at any point in this process, rather they are active participants in their development, engaged with their surroundings and responding selectively to what the environment affords. From this standpoint, developmental effects are the outcome of transactions with the environment. They are emergent phenomena, neither wholly independent of environmental influences, nor completely determined by them. It follows that the long-range utility and well-being of captive animals will be served well if they are able to select those with whom they will interact and modes of interaction that are appropriate to their level of development and current motivational state. This can generally be accomplished by permitting individuals to develop, at least through weaning, in the company of their biologic mothers within an approximation of a species-normal social group. When such latitude is impossible, the social environment should be arranged with the individuals' developmental levels as a primary concern.


Dietary supplement users vary in attitudes and sources of dietary supplement information in East and West geographic regions: a cross-sectional study.
Over 50% of adults currently use dietary supplements (DS) but manufacturers do not have to prove the safety or efficacy of a DS before it is marketed. Therefore, consumers may be exposed to inaccurate DS information, may lack confidence in choosing appropriate DS and may seek advice for usage. The objective of this study was to examine trends in usage, attitudes, and sources of information regarding DS according to geographic location, demographic group, and lifestyle choices. Eligible individuals completed a 10-item researcher-developed survey tool to determine DS use, sources of DS information, and DS-related knowledge and attitudes over the previous year. Healthy participants (637 individuals aged 21-75 years) from two population-based cohorts that had been recruited for lipoprotein assessment studies at Tufts University in Boston, Massachusetts and University of California at Davis. Outcome measures included participants' use, beliefs regarding essentiality of DS, confidence in choosing appropriate DS, and sources of information on DS. Univariate and multivariate logistic regression were utilized to examine differences in survey responses between groups. Of the total population 72.7% reported taking dietary supplements in the previous year. Those living on the West Coast (80.3%) had greater use than those living on the East Coast (60.7%). Those on the East Coast were more likely to believe DS were essential to health (48.7%) and to feel confident in choosing DS that were appropriate for them (51.0%). Overall, physicians were the most frequent source of DS information for more than 50% of participants on both coasts. Because DS usage is widespread, health care providers and nutrition educators must encourage patients to discuss their DS use and be equipped to provide information conducive to safe, efficacious consumption. Tailoring interventions for healthcare providers, media sources, industry, and the public may allow for dissemination of up-to-date information regarding DS.


Cardiac involvement in myotonic dystrophy.
Myotonic dystrophy (DM) is an inherited progressive muscle disorder caused by defects in muscle proteins. As the incidence of this condition is low, not many are familiar with the multisystem involvement. At times, cardiac disease may even be the predominant manifestation in the form of arrhythmias, conduction defects, and cardiomyopathies. The progression of the disease can lead to sudden, unpredictable death. Thus, it is important to identify this subgroup and treat accordingly. To identify patients with DM and assess their risk for sudden cardiac death. Nine patients previously diagnosed with muscular dystrophy were evaluated by cardiologists for various reasons, from a general follow-up to cardiac arrest. All of them had electrocardiograms (EKG) and 2-D echocardiograms, and seven of them had further electrophysiological (EP) studies. Of the nine patients with DM, eight had EKG evidence of conduction abnormalities ranging from first-degree heart block to complete heart block. Of the seven who had EP studies, five had inducible ventricular tachycardia requiring immediate cardioversion and implantable cardioverter defibrillator (ICD) implant. Two of them underwent permanent pacemaker placement due to complete heart block and infra-Hissian block. The remaining two patients opted for a conservative approach with yearly EKG monitoring. Because one-third of the cardiac deaths in patients with DM are sudden, there is a strong need to identify these patients and intervene in those at high risk. Prophylactic pacemaker placement is recommended even in those with minimal conduction system abnormality. However, the common practice is to identify patients at high risk of conduction abnormalities by EP studies and then provide them with prophylactic invasive strategies.


Separate channels for processing form, texture, and color: evidence from FMRI adaptation and visual object agnosia.
Previous neuroimaging research suggests that although object shape is analyzed in the lateral occipital cortex, surface properties of objects, such as color and texture, are dealt with in more medial areas, close to the collateral sulcus (CoS). The present study sought to determine whether there is a single medial region concerned with surface properties in general or whether instead there are multiple foci independently extracting different surface properties. We used stimuli varying in their shape, texture, or color, and tested healthy participants and 2 object-agnosic patients, in both a discrimination task and a functional MR adaptation paradigm. We found a double dissociation between medial and lateral occipitotemporal cortices in processing surface (texture or color) versus geometric (shape) properties, respectively. In Experiment 2, we found that the medial occipitotemporal cortex houses separate foci for color (within anterior CoS and lingual gyrus) and texture (caudally within posterior CoS). In addition, we found that areas selective for shape, texture, and color individually were quite distinct from those that respond to all of these features together (shape and texture and color). These latter areas appear to correspond to those associated with the perception of complex stimuli such as faces and places.


Erythropoietic response to oral iron in patients with nondialysis-dependent chronic kidney disease in the FIND-CKD trial .
To evaluate erythropoietic response rates to oral iron over time in iron-deficient anemic patients with nondialysis-dependent chronic kidney disease (ND-CKD). FIND-CKD was a 1-year, randomized, multicenter trial of iron therapy in patients with ND-CKD, anemia, and iron deficiency, without erythropoiesis-stimulating agent (ESA) therapy. Patients with active infection or C-reactive protein > 20 mg/L were excluded. In this post-hoc analysis, response was defined as ≥ 1 g/dL increase in hemoglobin (Hb) from baseline, before initiation of alternative anemia therapy (i.e., ESA, transfusion, or intravenous iron). 308 patients received oral iron (200 mg elemental iron/day). Mean (SD) Hb at baseline was 10.4 (0.7) g/dL. At week 4, Hb data were available from 292 patients without alternative anemia therapy: 63/292 (21.6%) showed a response. Among the 229 nonresponders at week 4, 48.8% showed a cumulative response on ≥ 1 occasion by week 52 (11.1%, 19.9%, 25.9%, and 28.7% had a response at weeks 8, 12, 24, and 52, respectively), and 27.9% had received alternative iron therapy by week 52. Baseline levels of Hb, ferritin, and transferrin saturation were lower in responders than in nonresponders. Neither concomitant medication nor adherence (as assessed by medication count) was substantially different between early responders and nonresponders. Four weeks after starting oral iron therapy, only 21.6% of anemic patients with ND-CKD and iron deficiency showed an Hb increase of at least 1 g/dL. Among early nonresponders, < 30% responded at any subsequent time point. Earlier consideration of alternative therapy could improve anemia management in this population. .


Management of descending duodenal injuries secondary to laparoscopic cholecystectomy.
To report our experience of managing patients affected by descending duodenal injuries secondary to laparoscopic cholecystectomy and to review the literature. Analysis of 5 cases of descending duodenal injury as a consequence of laparoscopic cholecystectomy managed between June 1992 and September 2006. The median age was 59 (range 49-67) years. In all cases an emergency laparotomy showed an injury to the descending duodenum. Two patients underwent direct suture of the duodenum and external biliary drainage through a T-tube, 1 case underwent a duodenojejunostomy and in another a duodenopancreatectomy. The latter patient underwent drainage of the duodenum with a Petzer tube, followed 5 days later by gastric resection, closure of the duodenal stump and repair of the duodenal wound by suture. The median postoperative stay was 45 days and 1 patient died. Descending duodenal injuries are extremely rare complications of laparoscopic cholecystectomy with potentially fatal consequences if not promptly recognized and treated. The site of the descending duodenal injury is important for determining the surgical approach.


Additive Neuroprotection of a 20-HETE Inhibitor with Delayed Therapeutic Hypothermia after Hypoxia-Ischemia in Neonatal Piglets.
The severity of perinatal hypoxia-ischemia and the delay in initiating therapeutic hypothermia limit the efficacy of hypothermia. After hypoxia-ischemia in neonatal piglets, the arachidonic acid metabolite 20-hydroxyeicosatetraenoic acid (20-HETE) has been found to contribute to oxidative stress at 3 h of reoxygenation and to eventual neurodegeneration. We tested whether early administration of a 20-HETE synthesis inhibitor after reoxygenation augments neuroprotection with 3-hour delayed hypothermia. In two hypothermic groups, whole body cooling from 38.5 to 34°C was initiated 3 h after hypoxia-ischemia. Rewarming occurred from 20 to 24 h; then anesthesia was discontinued. One hypothermic group received a 20-HETE inhibitor at 5 min after reoxygenation. A sham-operated group and another hypoxia-ischemia group remained normothermic. At 10 days of recovery, resuscitated piglets with delayed hypothermia alone had significantly greater viable neuronal density in the putamen, caudate nucleus, sensorimotor cortex, CA3 hippocampus, and thalamus than did piglets with normothermic recovery, but the values remained less than those in the sham-operated group. In piglets administered the 20-HETE inhibitor before hypothermia, the density of viable neurons in the putamen, cortex and thalamus was significantly greater than in the group with hypothermia alone. Cytochrome P450 4A, which can synthesize 20-HETE, was expressed in piglet neurons in these regions. We conclude that early treatment with a 20-HETE inhibitor enhances the therapeutic benefit of delayed hypothermia in protecting neurons in brain regions known to be particularly vulnerable to hypoxia-ischemia in term newborns.


Blood pressure measurements in Israeli Arab children and adolescents.
Hypertension is one of the most prevalent vascular diseases in the adult population. It is an important determinant of atherosclerosis in adolescents and young adults. There is to date no information on blood pressure in children of the Israeli Arab population. To study blood pressure in Israeli Arab children and adolescents. Blood pressure measurements were taken in the supine position in 4,488 Israeli Arab children and adolescents of both sexes aged 6-17 years. Height and weight were also determined. Correlation was investigated between systolic and diastolic blood pressure, body mass index, gender, and age. The systolic and diastolic blood pressures were similar in both sexes for all age groups up to 14 years of age. Systolic blood pressure was significantly (P < 0.001) higher in males aged 15-17 years (120 +/- 13 vs. 111 +/- 12 mmHg, 123 +/- 13 vs. 113 +/- 14.0 mmHg, and 123 +/- 18 vs. 111 +/- 14 mmHg, respectively). Diastolic blood pressure was higher in males aged 15-17, with a statistically significant difference for age 17 only (75 +/- 12 vs. 69 +/- 13 mmHg). Blood pressure was elevated in 322 students in the initial screening (7.17%), with a decrease to 2.18% when this group was rescreened 2 weeks later. The systolic blood pressure in our group is higher than that in Jewish Israeli children of Asian and North African origin, and in American children. It is similar to the systolic blood pressure of European children and Jewish children born in Israel. The diastolic blood pressure in our group is higher than that in all groups of Israeli Jewish children and American children of different ethnic groups. Israeli Arab children and adolescents have higher blood pressure levels than their Israeli Jewish counterparts. Further studies are required to confirm this observation.


Impact of Deceased Donor Cardiac Arrest Time on Postpancreas Transplant Graft Function and Survival.
Transplantation of pancreas allografts from donors that have experienced preprocurement cardiopulmonary arrest (PPCA) is not common, though use of PPCA grafts is routine in liver and kidney transplantation. This article reviews a large number of PPCA pancreas grafts at a single center and reports posttransplant outcomes including early graft dysfunction, length of hospital stay, rejection, and early and late graft survival. Preprocurement cardiopulmonary arrest, arrest time, and donor and recipient pancreatic enzyme levels were collected from electronic and written medical records. The PPCA donors were stratified into 4 groups: none, less than 20 minutes, 20-39 minutes, and 40 minutes or greater. Graft survival was assessed at 7 and 90 days and at 1 year. Long-term graft survival was assessed by Cox regression analysis. The records of 606 pancreas transplants were reviewed, including 328 (54%) simultaneous pancreas and kidney transplants. Preprocurement cardiopulmonary arrest occurred in 176 donors (29%; median time, 20 minutes). Median peak donor lipase was higher in PPCA donors (40 μ/L vs 29 μ/L, P = 0.02). Posttransplant, peak recipient amylase, and lipase levels were similar (P = 0.63). Prolonged arrest time (>40 minutes) was associated with higher donor peak lipase and lower recipient peak amylase (P = 0.05 for both). Stratified by donor arrest time, there was no difference in 7-day, 90-day, or 1-year graft survival. Cox regression comparing the 4 groups demonstrated no statistical difference in 10-year survival. These results support transplantation of pancreas allografts from PPCA donors. Prolonged asystole was associated with higher peak donor serum lipase but lower peak recipient serum amylase. There were no differences in allograft survival.


The narrative reconstruction of psychotherapy and psychological health.
When people complete psychotherapy, they carry the story of the experience with them. This retrospective reconstruction serves several psychological purposes, including contributing to narrative identity and influencing the maintenance of therapeutic gains after termination. Based on a prior qualitative investigation of therapy narratives (Adler & McAdams, 2007a), a new sample of 104 former clients wrote about their psychotherapy after treatment end. Quantitative analyses indicated that the retrospective narratives of participants high in subjective well-being focused on the protagonist's agency in struggling with a discrete problem. In addition, the narratives of participants high in ego development described a coherent story of growth. These findings suggest that the stories clients construct about psychotherapy reliably vary depending on their psychological health.


Chitosan-Grafted-Poly(N-vinylcaprolactam)-Decorated Fe3O4@SiO2 Core-Shell Nanoformulation as an Efficient Drug Delivery System for Poorly Soluble Drugs.
Hydrocortisone, a commonly used anti-inflammatory drug, has limited aqueous solubility and several side effects. To address this challenge, as a proof-of-concept, this article demonstrates the development of a controlled-release drug delivery system (DDS) for hydrocortisone using chitosan-grafted poly(N-vinylcaprolactam) (CS-g-PNVCL)-coated core-shell Fe3O4@SiO2 nanoformulations (NFs). Reported magnetic nanoparticles (NPs) were synthesized and modified with silica, PNVCL, and CS precursors to enhance the biocompatibility of DDS and drug-loading efficiency. The release rate of hydrocortisone from Fe3O4@SiO2@CS-g-PNVCL NFs was observed to be higher at lower pH values, and the smart polymer coating demonstrated temperature responsiveness, facilitating drug release at higher temperatures. Fe3O4@SiO2@CS-g-PNVCL NFs exhibited a cell viability of around 97.2 to 87.3% (5-100 μg/mL) after 24-48 h, while the hydrocortisone-NFs had a cell viability of around 93.2 to 82.3%. Our findings suggest that CS-g-PNVCL-coated Fe3O4@SiO2 NPs effectively enhance the solubility, loading capacity, and targeted delivery of poorly soluble drugs, thereby improving their therapeutic efficacy and bioavailability.