Application of a null-beamformer to source localisation in MEG data of deep brain stimulation.
In this paper, we present an analysis of magnetoencephalography (MEG) signals from a patient with whole-body chronic pain in order to investigate changes in neural activity induced by DBS. The patient is one of the few cases treated using DBS of the anterior cingulate cortex (ACC). Using MEG to reconstruct the neural activity of interest is challenging because of interference to the signal from the DBS device. We demonstrate that a null-beamformer can be used to localise neural activity despite artefacts caused by the presence of DBS electrodes and stimulus pulses. We subsequently verified the accuracy of our source localisation by correlating the predicted DBS electrode positions with their actual positions, previously identified using anatomical imaging. We also demonstrated increased activity in pain-related regions including the pre-supplementary motor area, brainstem periaqueductal gray and medial prefrontal areas when the patient was in pain compared to when the patient experienced pain relief.


Antiretroviral therapy using zidovudine, lamivudine, and efavirenz in South Africa: tolerability and clinical events.
To describe the safety and tolerability of zidovudine, lamivudine, and efavirenz in a low-income setting. We conducted a prospective cohort study in a workplace HAART programme in South Africa, which uses a first-line regimen of efavirenz, zidovudine, and lamivudine and provides routine clinical and laboratory monitoring 6-monthly pre-HAART and at 2, 6, 12, 24, 36, 48 weeks during HAART. We assessed the incidence of specified clinical and laboratory events (AIDS Clinical Trials Group grade 3 or higher) and associated regimen changes, hospitalizations, and deaths one year before HAART initiation and one year on-HAART using person-year analysis. Between November 2002 and October 2005, 853 subjects (98% male, median age 40 years, and median CD4 cell count at HAART initiation 186 cells/mul) met enrollment criteria. The incidence of events on-HAART was higher than pre-HAART for neutropenia and nausea/vomiting. Dizziness was common early after HAART initiation (not evaluated pre-HAART). Of those with neutropenia, 88% had no apparent clinical consequences. The incidence of anemia, hepatotoxicity, peripheral neuropathy, and rash was similar or higher pre-HAART than on-HAART. Mean hemoglobin rose during the time on-HAART and was higher at 24 and 48 weeks than at baseline (P < 0.001). This regimen was well tolerated with a short-term increase in neutropenia, nausea, and probably neurocerebellar events. Most significantly, in contrast to reports from high-income countries, we observed a long-term improvement in the hemoglobin concentration.


Are flatter diurnal cortisol rhythms associated with major depression and anxiety disorders in late adolescence? The role of life stress and daily negative emotion.
Alterations in hypothalamic-pituitary-adrenal (HPA) axis functioning have been associated with major depression disorder (MDD) and some anxiety disorders. Few researchers have tested the possibility that high levels of recent life stress or elevations in negative emotion may partially account for the HPA axis alterations observed in these disorders. In a sample of 300 adolescents from the Youth Emotion Project, we examined associations between MDD and anxiety disorders, dimensional measures of internalizing symptomatology, life stress, mood on the days of cortisol testing, and HPA axis functioning. Adolescents with a past MDD episode and those with a recent MDD episode comorbid with an anxiety disorder had flatter diurnal cortisol slopes than adolescents without a history of internalizing disorders. Higher reports of general distress, a dimension of internalizing symptomatology, were also associated with flatter slopes. Negative emotion, specifically sadness and loneliness, was associated with flatter slopes and partially accounted for the associations between comorbid MDD and anxiety disorders and cortisol. The associations between past MDD and cortisol slopes were not accounted for by negative emotion, dimensional variation in internalizing symptomatology, or levels of life stress, indicating that flatter cortisol slopes may also be a "scar" marker of past experiences of MDD.


An applied ecological framework for evaluating infrastructure to promote walking and cycling: the iConnect study.
Improving infrastructure for walking and cycling is increasingly recommended as a means to promote physical activity, prevent obesity, and reduce traffic congestion and carbon emissions. However, limited evidence from intervention studies exists to support this approach. Drawing on classic epidemiological methods, psychological and ecological models of behavior change, and the principles of realistic evaluation, we have developed an applied ecological framework by which current theories about the behavioral effects of environmental change may be tested in heterogeneous and complex intervention settings. Our framework guides study design and analysis by specifying the most important data to be collected and relations to be tested to confirm or refute specific hypotheses and thereby refine the underlying theories.


Meritocratic and fair? The discourse of UK and Australia's widening participation policies.
Globally, people with the academic and personal attributes to successfully study medicine experience disadvantages associated with sociodemographic factors. Governments have attempted to address this issue via macrolevel policies aimed at widening participation (WP) to medicine. These policies differ by country, suggesting much can be learned from examining and comparing international policy discourses of WP. Our question was: How are discourses of WP to higher and medical education positioned in the UK and Australia? A systematic search strategy was guided by five a priori themes inspired by United Nations Sustainability Goals (2015). Seventeen policy documents (UK n = 9, Australia n = 8) published between 2008 and 2018 were identified. Analysis involved two over-arching, iterative stages: a document analysis then a Foucauldian critical discourse analysis, the latter with the aim of unveiling the power dynamics at play within policy-related discourses. Discourses of social mobility and individual responsibility within a meritocracy are still paramount in the UK. In contrast, the dominant discourse in Australia is social accountability in achieving equity and workforce diversity, prioritising affirmative action and community values. Similarities between the two countries in terms of WP policy and policy levers have changed over time, linked to the divergence of internal drivers for societal change. Both nations recognise tensions inherent in striving to achieve both local and global goals, but Australia appears to prioritise community values in working towards 'nation building' whereas in the UK the focus on individuality and meritocracy at times seems at odds with achieving parity for disadvantaged individuals. WP policies and practices are situated and contextual so caution must be taken when extrapolating lessons from one context to another. The history of a country and the nature of marginalisation in that country must be scrutinised when trying to understand what drives WP policy.


Factors affecting the prevalence of strongly and weakly carcinogenic and lower-risk human papillomaviruses in anal specimens in a cohort of men who have sex with men (MSM).
MSM are at higher risk for invasive anal cancer. Twelve human papillomaviruses (HPVs) cause cervical cancer in women (Group 1 high-risk HPVs (hrHPVs)) and 13 HPVs are probable/possible causes (Group 2 hrHPVs) of cervical malignancy. HPVs rarely associated with malignancy are classified as lower-risk HPVs (lrHPVs). Dacron-swab anal-cytology specimens were collected from and data complete for 97% (1262/1296) of Multicenter AIDS Cohort Study (MACS) men tested for HPVs using the Linear Array assay. Multivariate Poisson regression analyses estimated adjusted prevalence ratios for Group 1/2 hrHPVs and lrHPVs, controlling for the effects of age, race, ethnicity, sexual partnerships, smoking; HIV-infection characteristics, treatment, and immune status among HIV-infected men. HIV-infected men showed 35-90% higher prevalence of Group 1/2 hrHPVs and lrHPVs than HIV-uninfected men, and higher prevalence of multi-Type, and multiple risk-group infections. CD4+ T-cell count was inversely associated with HPV Group 2 prevalence (p<0.0001). The number of receptive anal intercourse (RAI) partners reported in the 24 months preceding HPV testing predicted higher prevalence of Group 1/2 hrHPVs. Men reporting ≥30 lifetime male sex partners before their first MACS visit and men reporting ≥1 RAI partners during the 24 months before HPV testing showed 17-24% and 13-17% higher prevalence of lrHPVs (p-values ≤0.05). Men reporting smoking between MACS visit 1 and 24 months before HPV testing showed 1.2-fold higher prevalence of Group 2 hrHPVs (p = 0.03). Both complete adherence to CART (p = 0.02) and HIV load <50 copies/mL (p = 0.04) were protective for Group 1 hrHPVs among HIV-infected men. HIV-infected men more often show multi-type and multi-group HPV infections HIV-uninfected men. Long-term mutual monogamy and smoking cessation, generally, and CART-adherence that promotes (HIV) viremia control and prevents immunosuppression, specifically among HIV-infected MSM, are important prevention strategies for HPV infections that are relevant to anal cancer.


Dreams of the Rarebit Fiend: food and diet as instigators of bizarre and disturbing dreams.
In the early 1900s, the Dream of the Rarebit Fiend comic strip conveyed how the spicy cheese dish Welsh rarebit leads to bizarre and disturbing dreams. Today, the perception that foods disturb dreaming persists. But apart from case studies, some exploratory surveys, and a few lab studies on how hunger affects dreaming, there is little empirical evidence addressing this topic. The present study examines three aspects of the food/dreaming relationship; it attempts to: (1) assess the prevalence of the perception of food-dependent dreaming and the types of foods most commonly blamed; (2) determine if perceived food-dependent dreaming is associated with dietary, sleep or motivational factors; and (3) explore whether these factors, independent of food/dreaming perceptions, are associated with reports of vivid and disturbing dreams. Three hundred and ninety six students completed questionnaires evaluating sleep, dreams, and dietary habits and motivations. Items queried whether they had noticed if foods produced bizarre or disturbing dreams and if eating late at night influenced their dreams. The perception of food-dependent dreaming had a prevalence of 17.8%; with dairy products being the most frequently blamed food category (39-44%). Those who perceived food-dependent dreaming differed from others by reporting more frequent and disturbing dreams, poorer sleep, higher coffee intake, and lower Intuitive Eating Scale scores. Reports of disturbing dreams were associated with a pathological constellation of measures that includes poorer sleep, binge-eating, and eating for emotional reasons. Reports of vivid dreams were associated with measures indicative of wellness: better sleep, a healthier diet, and longer times between meals (fasting). Results clarify the relationship between food and dreaming and suggest four explanations for the perception of food-dependent dreaming: (1) food specific effects; (2) food-induced distress; (3) folklore influences, and (4) causal misattributions. Research and clinical implications are discussed.


Visfatin is regulated by rosiglitazone in type 2 diabetes mellitus and influenced by NFκB and JNK in human abdominal subcutaneous adipocytes.
Visfatin has been proposed as an insulin-mimicking adipocytokine, predominantly secreted from adipose tissue and correlated with obesity. However, recent studies suggest visfatin may act as a proinflammatory cytokine. Our studies sought to determine the significance of this adipocytokine and its potential role in the pathogenesis of T2DM. Firstly, we examined the effects of diabetic status on circulating visfatin levels, and several other adipocytokines, demonstrating that diabetic status increased visfatin*, TNF-α*** and IL-6*** compared with non-diabetic subjects (*p<0.05, **p<0.01, ***p<0.001, respectively). We then assessed the effects of an insulin sensitizer, rosiglitazone (RSG), in treatment naïve T2DM subjects, on circulating visfatin levels. Our findings showed that visfatin was reduced post-RSG treatment [vs. pre-treatment (*p<0.05)] accompanied by a reduction in HOMA-IR**, thus implicating a role for insulin in visfatin regulation. Further studies addressed the intracellular mechanisms by which visfatin may be regulated, and may exert pro-inflammatory effects, in human abdominal subcutaneous (Abd Sc) adipocytes. Following insulin (Ins) and RSG treatment, our in vitro findings highlighted that insulin (100 nM), alone, upregulated visfatin protein expression whereas, in combination with RSG (10 nM), it reduced visfatin*, IKKβ** and p-JNK1/2*. Furthermore, inhibition of JNK protein exacted a significant reduction in visfatin expression (**p<0.01), whilst NF-κB blockade increased visfatin (*p<0.05), thus identifying JNK as the more influential factor in visfatin regulation. Additional in vitro analysis on adipokines regulating visfatin showed that only Abd Sc adipocytes treated with recombinant human (rh)IL-6 increased visfatin protein (*p<0.05), whilst rh visfatin treatment, itself, had no influence on TNF-α, IL-6 or resistin secretion from Sc adipocytes. These data highlight visfatin's regulation by insulin and RSG, potentially acting through NF-κB and JNK mechanisms, with only rh IL-6 modestly affecting visfatin regulation. Taken together, these findings suggest that visfatin may represent a pro-inflammatory cytokine that is influenced by insulin/insulin sensitivity via the NF-κB and JNK pathways.


CORONIS - International study of caesarean section surgical techniques: the follow-up study.
The CORONIS Trial was a 2×2×2×2×2 non-regular, fractional, factorial trial of five pairs of alternative caesarean section surgical techniques on a range of short-term outcomes, the primary outcome being a composite of maternal death or infectious morbidity. The consequences of different surgical techniques on longer term outcomes have not been well assessed in previous studies. Such outcomes include those related to subsequent pregnancy: mode of delivery; abnormal placentation (e.g. accreta); postpartum hysterectomy, as well as longer term pelvic problems: pain, urinary problems, infertility. The Coronis Follow-up Study aims to measure and compare the incidence of these outcomes between the randomised groups at around three years after women participated in the CORONIS Trial. This study will assess the following null hypotheses: In women who underwent delivery by caesarean section, no differences will be detected with respect to a range of long-term outcomes when comparing the following five pairs of alternative surgical techniques evaluated in the CORONIS Trial: 1. Blunt versus sharp abdominal entry. 2. Exteriorisation of the uterus for repair versus intra-abdominal repair. 3. Single versus double layer closure of the uterus. 4. Closure versus non-closure of the peritoneum (pelvic and parietal). 5. Chromic catgut versus Polyglactin-910 for uterine repair. The outcomes will include (1) women's health: pelvic pain; dysmenorrhoea; deep dyspareunia; urinary symptoms; laparoscopy; hysterectomy; tubal/ovarian surgery; abdominal hernias; bowel obstruction; infertility; death. (2) Outcomes of subsequent pregnancies: inter-pregnancy interval; pregnancy outcome; gestation at delivery; mode of delivery; pregnancy complications; surgery during or following delivery. The results of this follow-up study will have importance for all pregnant women and for health professionals who provide care for pregnant women. Although the results will have been collected in seven countries with limited health care resources (Argentina, Chile, Ghana, India, Kenya, Pakistan, Sudan) any differences in outcomes associated with different surgical techniques are likely to be generalisable throughout the world. ISRCTN31089967.


Curcumin inhibits proliferation, invasion, angiogenesis and metastasis of different cancers through interaction with multiple cell signaling proteins.
Because most cancers are caused by dysregulation of as many as 500 different genes, agents that target multiple gene products are needed for prevention and treatment of cancer. Curcumin, a yellow coloring agent in turmeric, has been shown to interact with a wide variety of proteins and modify their expression and activity. These include inflammatory cytokines and enzymes, transcription factors, and gene products linked with cell survival, proliferation, invasion, and angiogenesis. Curcumin has been found to inhibit the proliferation of various tumor cells in culture, prevents carcinogen-induced cancers in rodents, and inhibits the growth of human tumors in xenotransplant or orthotransplant animal models either alone or in combination with chemotherapeutic agents or radiation. Several phase I and phase II clinical trials indicate that curcumin is quite safe and may exhibit therapeutic efficacy. These aspects of curcumin are discussed further in detail in this review.


Proteomic characterization of pleural effusion, a specific host niche of Mycoplasma mycoides subsp. mycoides from cattle with contagious bovine pleuropneumonia (CBPP).
Mycoplasma mycoides subsp. mycoides (Mmm) is the causative agent of contagious bovine pleuropneumonia (CBPP), a severe pleuropneumonia in cattle. The abnormal accumulation of pleural fluid, called pleural effusion (PE), is one of the characteristics of this disease. We performed a proteomic analysis of seven PE samples from experimentally infected cattle and characterized their composition with respect to bovine and Mmm proteins. We detected a total of 963 different bovine proteins. Further analysis indicated a strong enrichment of proteins involved in antigen processing, platelet activation and degranulation and apoptosis and an increased abundance of acute phase proteins.With regard to the pathogen, up to 108 viable mycoplasma cells per ml were detected in the PE supernatant. The proteomic analysis revealed 350 mycoplasma proteins, including proteins involved in virulence-associated processes like hydrogen peroxide (H2O2) production and capsule synthesis. The bovine proteins detected will aid to characterize the inflammasome during an acute pleuropneumonia in cattle and the identified mycoplasma proteins will serve as baseline data to be compared with in vitro studies to improve our understanding of pathogenicity mechanisms. Based on our results, we named the pleural effusion an "in vivo niche" of Mmm during the acute phase of CBPP. Biological significance: This is the first study on bovine pleural effusions derived from an infectious disease and the first approach to characterize the proteome of Mycoplasma mycoides in vivo. This study revealed a high number of viable Mmm cells in the pleural effusion. The bovine pleural effusion proteome during Mmm infection is qualitatively similar to plasma, but differs with respect to high abundance of acute phase proteins. On the other hand,Mmm in its natural host produces proteins involved in capsule synthesis, H2O2 production and induction of inflammatory response, supporting previous knowledge on mechanisms underlying the survival and virulence of this pathogen while inside the natural host. This knowledge forms a profound basis for testing the identified protein candidates for diagnostics or vaccines.


Chemoattractant-induced activation of c-fos gene expression in human monocytes.
Human monocytes use the products of phosphoinositide hydrolysis (1,2-diacylglycerol and inositol 1,4,5-triphosphate) as second messengers to trigger rapid cellular activation during the occupancy of chemoattractant receptors. The effect of chemoattractants on modulation of gene expression in monocytes was examined in this study. The chemoattractants FMLP and platelet-activating factor induced the progressive increase of c-fos RNA to 6-15-fold over those of control within 30 min after treatment. Similar kinetics of c-fos gene activation was also observed when cells were treated with PMA or sn-1,2-dioctanoylglycerol, but not with the calcium mobilizer ionomycin, suggesting a role for protein kinase C in gene regulation by chemoattractant receptors. Activation of c-fos gene expression by FMLP is mediated through a pertussis toxin-sensitive G protein, since pertussis toxin treatment of the cells blocked the induction of the c-fos gene by FMLP but not PMA. The level of c-myc RNA was slightly decreased after 1 h of treatment with chemoattractants, but not with PMA or diacylglycerol. This implies that chemoattractant receptor occupancy generates signals beyond protein kinase C activation that are capable of selectively downregulating monocyte gene expression. The effect of FMLP and PMA on the accumulation of c-fos RNA appears to result from altering both the rate of transcription and message stability. These observations indicate that signals generated through chemoattractant receptor occupancy may regulate monocyte function at the genetic level.


Imitation by social interaction? Analysis of a minimal agent-based model of the correspondence problem.
One of the major challenges faced by explanations of imitation is the "correspondence problem": how is an agent able to match its bodily expression to the observed bodily expression of another agent, especially when there is no possibility of external self-observation? Current theories only consider the possibility of an innate or acquired matching mechanism belonging to an isolated individual. In this paper we evaluate an alternative that situates the explanation of imitation in the inter-individual dynamics of the interaction process itself. We implemented a minimal model of two interacting agents based on a recent psychological study of imitative behavior during minimalist perceptual crossing. The agents cannot sense the configuration of their own body, and do not have access to other's body configuration, either. And yet surprisingly they are still capable of converging on matching bodily configurations. Analysis revealed that the agents solved this version of the correspondence problem in terms of collective properties of the interaction process. Contrary to the assumption that such properties merely serve as external input or scaffolding for individual mechanisms, it was found that the behavioral dynamics were distributed across the model as a whole.


Neoplastic diseases of the spermatic cord: an overview of pathological features, evaluation, and management.
Extracellular tumors found with the spermatic cord, known as neoplasms, are usually identified to be benign. However, the accurate and timely diagnosis of spermatic cord masses is highly crucial, especially when most results are often overlooked or unclear. In this review, we discuss the anatomy and embryology of the spermatic cord. Upon rooting these fundamental concepts, we discuss an array of benign and malignant neoplastic tumors, including their origin, pathological features, clinical evaluation and management, as well as other case-specific characteristics of unique presentation. Many of these neoplasms are based on local neurological, vascular, muscular, bone, soft tissue, or lymphatic origin, while others have metastasized from particular areas of the body.


SU-D-211-04: Sector Intensity Modulated (SIM) Gamma Knife Stereotactic Radiosurgery.
The latest Gamma Knife (GK) system, Perfexion, consists of 192 Co-60 sources divided into eight sectors. Treatment delivery includes multiple shots placed at different positions. For every shot, each sector can be either blocked or open with four different aperture sizes. However, the beam-on time is designed to be fixed. We proposed an innovative concept, Sector Intensity Modulated (SIM) Gamma Knife by dynamically varying the beam-on time for each individual sector to improve stereotactic radiosurgery planning quality. The anatomic structures and dose matrices from each sector for every shot were obtained from the GK workstation. The beam-on time for each sector was decomposed with various discrete levels and brute-force algorithm was used to get the optimal solution. The resulting SIM plan was then re-entered into the GK workstation. Six indices were used to benchmark the plan quality: Coverage, Conformality, Gradient, Maximum Dose(s) to critical structure(s), Volume receiving over 8 and 12 Gy. All the SIM plans in comparison with the original plans were further reviewed by an experienced oncologist. The simulations were tested on various pituitary adenoma cases. Results consistently showed that SIM yielded better plans with all quantitative indices improved compared to original plan. It provides better conformality, quicker drop off of the isodose line outside the tumor, lower doses to the critical structures as optical- nerve/chiasm while maintaining at least 99% coverage of the tumor. Results were more favorable according to oncologist's view. In particular, up to 20% or 0.6 cc volume decrease in healthy tissue receiving 8 Gy was observed. This may translate into clinically observable reduction in acute/late toxicities. Our preliminary results show that Sector Intensity Modulated Gamma Knife offers superior treatment plans compared to the originally delivered plans. Further works as adding dynamic shot location and dynamic shot shaping will be discussed.


EXPERIMENTAL BRONCHOPNEUMONIA BY INTRABRONCHIAL INSUFFLATION.
When intrabronchial insufflation of pure cultures of the streptococcus or of the influenza bacillus is properly carried out, it produces without fail a pneumonic lesion. This lesion is similar in its nature to the one known in human pathology as bronchopneumonia, and differs materially from the pneumonic lesion produced experimentally by the intrabronchial insufflation of pure cultures of the pneumococcus. Considering the fact that none of the dogs used in the experiments with the pneumococcus and none of those used in the present investigation were selected or prepared in any way, the conclusion seems to be unavoidable that the proper invasion of the microörganism is the determining factor in the development of pneumonia, the condition of the animal being only a minor element in this regard. Furthermore, since different organisms introduced in the same way and under conditions which are apparently the same produced distinctly different pneumonic lesions in animals of the same species, the further conclusion presents itself that the different types of pneumonia are produced by specifically different bacteria. However, further investigation may show that the differences in the nature of the lesion are due rather to the degree of virulence of the causative microörganism than to differences in the species; that is, that different lesions may possibly be produced by organisms of the same species, provided they possess different degrees of virulence. Further experimentation may also show that the condition of the animal and of the affected organ which, in the onset and development of the pneumonic disease, is, perhaps, unimportant, may be the leading factor in determining the course and outcome of the disease.


Trends in Pediatric Emergency Department Visits for Mental Health Conditions and Disposition by Presence of a Psychiatric Unit.
To examine trends in mental health (MH) visits to pediatric emergency departments (EDs) and identify whether ED disposition varies by presence of a hospital inpatient psychiatric unit (IPU). Cross-sectional study of 8,479,311 ED visits to 35 children's hospitals from 2012 to 2016 for patients aged 3 to 21 years with a primary MH or non-MH diagnosis. Multivariable generalized estimating equations and bivariate Rao-Scott chi-square tests were used to examine trends in ED visits and ED disposition by IPU status, adjusted for clustering by hospital. From 2012 to 2016, hospitals experienced a greater increase in ED visits with a primary MH versus non-MH diagnosis (50.7% vs 12.7% cumulative increase, P < .001). MH visits were associated with patients who were older, female, white non-Hispanic, and privately insured compared with patients of non-MH visits (all P < .001). Forty-four percent of MH visits in 2016 had a primary diagnosis of depressive disorders or suicide or self-injury, and the increase in visits was highest for these diagnosis groups (depression: 109.8%; suicide or self-injury: 110.2%). Among MH visits, presence of a hospital IPU was associated with increased hospitalizations (34.6% vs 22.5%, P < .001) and less transfers (9.2% vs 16.2%, P < .001). The increase in ED MH visits from 2012 to 2016 was 4 times greater than non-MH visits at US children's hospitals and was primarily driven by patients diagnosed with depressive disorders and suicide or self-injury. Our findings have implications for strategic planning in tertiary children's hospitals dealing with a rising demand for acute MH care.


Nanofibers and nanoparticles from the insect-capturing adhesive of the Sundew (Drosera) for cell attachment.
The search for naturally occurring nanocomposites with diverse properties for tissue engineering has been a major interest for biomaterial research. In this study, we investigated a nanofiber and nanoparticle based nanocomposite secreted from an insect-capturing plant, the Sundew, for cell attachment. The adhesive nanocomposite has demonstrated high biocompatibility and is ready to be used with minimal preparation. Atomic force microscopy (AFM) conducted on the adhesive from three species of Sundew found that a network of nanofibers and nanoparticles with various sizes existed independent of the coated surface. AFM and light microscopy confirmed that the pattern of nanofibers corresponded to Alcian Blue staining for polysaccharide. Transmission electron microscopy identified a low abundance of nanoparticles in different pattern form AFM observations. In addition, energy-dispersive X-ray spectroscopy revealed the presence of Ca, Mg, and Cl, common components of biological salts. Study of the material properties of the adhesive yielded high viscoelasticity from the liquid adhesive, with reduced elasticity observed in the dried adhesive. The ability of PC12 neuron-like cells to attach and grow on the network of nanofibers created from the dried adhesive demonstrated the potential of this network to be used in tissue engineering, and other biomedical applications. This discovery demonstrates how a naturally occurring nanofiber and nanoparticle based nanocomposite from the adhesive of Sundew can be used for tissue engineering, and opens the possibility for further examination of natural plant adhesives for biomedical applications.


Rectus femoris distal tendon resection improves knee motion in patients with spastic diplegia.
Children with spastic diplegia frequently show excessive knee extension (stiff-knee gait) throughout swing phase, which may interfere with foot clearance. Abnormal rectus femoris activity is commonly associated with a stiff-knee gait. Rectus femoris transfer has been recommended to enhance knee flexion during swing. However, recent studies suggest the transfer does not generate a knee flexor moment but diminishes knee extension moment in swing and MRI studies show the transferred tendons can be constrained by scarring to underlying muscles. Thus, it is possible knee flexion would be improved by distal rectus release rather than transfer since it would not be adherent to the underlying muscles. We therefore determined whether rectus femoris distal tendon resection improves knee ROM and kinematic characteristics of stiff-knee gait in patients with spastic diplegia. We studied 45 patients who underwent rectus femoris distal tendon resection as a part of multilevel surgery. Rectus femoris procedures were indicated based on kinematic characteristics of stiff-knee gait. All patients were walkers and had a mean age at surgery of 13 years (range, 6-22 years). We obtained gait analyses before surgery and at mean 2-year followup. We based postoperative assessment on clinical evaluation and gait analysis data. At followup, rectus femoris distal tendon resection was associated with improved knee ROM and timing of peak knee flexion in swing, and the absolute values of peak knee flexion became normal for those patients who showed abnormal preoperative values. Kinematic parameters of stiff-knee gait improved after rectus femoris distal tendon resection. Given the preliminary nature of our report, we intend to study the same patients to assess outcomes at a longer followup. Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.


Biological activity of barbados cherry (acerola fruits, fruit of Malpighia emarginata DC) extracts and fractions.
Fractionation of barbados cherry (acerola fruit, a fruit of Malpighia emarginata DC.) extracts were performed by organic solvent extractions and column chromatographies, using two extraction methods. Higher cytotoxic activity was concentrated in fractions A4 and A6 (acetone extract), and H3 and HE3 (hexane extract). These four fractions showed higher cytotoxic activity against tumor cell lines such as human oral squamous cell carcinoma (HSC-2) and human submandibular gland carcinoma (HSG), when compared with that against normal cells such as human periodontal ligament fibroblasts (HPLF) and human gingival fibroblasts (HGF). HE2 (hexane extract), AE2 (ethyl acetate extract), AE3, AE4, AE5, A8, A9 and A10 showed some relatively higher anti-bacterial activity on the Gram-positive Staphylococcus epidermidis ATCC 1228 but were ineffective on the representative Gram-negative species E. coli and Ps. aeruginosa. The fractions were inactive against Helicobacter pylori, two representative Candida species, and human immunodeficiency virus (HIV). H3, H4 and HE3, which displayed higher tumor-specific cytotoxicity also showed higher multidrug resistance (MDR) reversal activity, than (+/-)-verapamil as positive control. ESR spectroscopy shows that the radical-mediated oxidation is not involved in the induction of tumor-specific cytotoxic activity. The tumor specific cytotoxic activity and MDR reversal activity of barbados cherry may suggest its possible application for cancer therapy.


Disrupted Blood-Retina Lysophosphatidylcholine Transport Impairs Photoreceptor Health But Not Visual Signal Transduction.
Retinal photoreceptor cells contain the highest concentration of docosahexaenoic acid (DHA) in our bodies, and it has been long assumed that this is critical for supporting normal vision. Indeed, early studies using DHA dietary restriction documented reduced light sensitivity by DHA-deprived retinas. Recently, it has been demonstrated that a major route of DHA entry in the retina is the delivery across the blood-retina barrier by the sodium-dependent lipid transporter, Mfsd2a. This discovery opened a unique opportunity to analyze photoreceptor health and function in DHA-deprived retinas using the Mfsd2a knock-out mouse as animal model. Our lipidome analyses of Mfsd2a-/- retinas and outer segment membranes corroborated the previously reported decrease in the fraction of DHA-containing phospholipids and a compensatory increase in phospholipids containing arachidonic acid. We also revealed an increase in the retinal content of monounsaturated fatty acids and a reduction in very long chain fatty acids. These changes could be explained by a combination of reduced DHA supply to the retina and a concomitant upregulation of several fatty acid desaturases controlled by sterol regulatory element-binding transcription factors, which are upregulated in Mfsd2a-/- retinas. Mfsd2a-/- retinas undergo slow progressive degeneration, with ∼30% of photoreceptor cells lost by the age of 6 months. Despite this pathology, the ultrastructure Mfsd2a-/- photoreceptors and their ability to produce light responses were essentially normal. These data demonstrate that, whereas maintaining the lysophosphatidylcholine route of DHA supply to the retina is essential for long-term photoreceptor survival, it is not important for supporting normal phototransduction.SIGNIFICANCE STATEMENT Phospholipids containing docosahexaenoic acid (DHA) are greatly enriched in the nervous system, with the highest concentration found in the light-sensitive membranes of photoreceptor cells. In this study, we analyzed the consequences of impaired DHA transport across the blood-retina barrier. We have found that, in addition to a predictable reduction in the DHA level, the affected retinas undergo a complex, transcriptionally-driven rebuilding of their membrane lipidome in a pattern preserving the overall saturation/desaturation balance of retinal phospholipids. Remarkably, these changes do not affect the ability of photoreceptors to produce responses to light but are detrimental for the long-term survival of these cells.


Impact of a water temperature shift on xenoma clearance and recovery time during a Loma salmonae (Microsporidia) infection in rainbow trout Oncorhynchus mykiss.
Previous studies have modelled the relationship between water temperature and the rate of sporulation as defined by xenoma formation during microsporidial gill disease (MGD) in salmon caused by Loma salmonae. Although offering insight into the epidemiology of MGD, a key unexplored area is the role of temperature in the rate of xenoma dissolution including spore release into the environment, and this is crucial to our ability to model horizontal transmission of MGD within confined net-pen populations of farmed salmon. Results from a previous trial suggested that xenoma dissolution may be dramatically hastened as water temperature declines, thus introducing a critical anomaly into any predictive exercise. The data generated herein was evaluated using the statistics of survival analysis to re-establish the baseline relationship of xenoma formation and dissolution relative to water temperature and to compare these results with those of previous studies. We infected 30 individuals of Oncorhynchus mykiss (Walbaum) with macerated xenoma-laden gill material, and afterwards allocated them to tanks with water temperatures of 11, 15, or 19 degrees C and monitored them through a disease cycle. Xenoma onset and clearance times were similar to previous findings with both events being accelerated at higher water temperatures, thereby suggesting a similar temperature response in the current strain to those used in previous studies. Another group of 45 fish was infected with L. salmonae and held at 15 degrees C until xenomas formed, and were subsequently shifted to 11, 15, or 19 degrees C. The median xenoma dissolution time in these tanks was 49, 35 and 28 d, respectively, similar to rates observed when water temperature remained constant. Thus we rejected the hypothesis that a sudden change in water temperature triggers rapid or anomalous xenoma dissolution.


A human DNA polymerase eta complex containing Rad18, Rad6 and Rev1; proteomic analysis and targeting of the complex to the chromatin-bound fraction of cells undergoing replication fork arrest.
DNA polymerase eta (Poleta) is responsible for efficient translesion synthesis (TLS) past cis-syn cyclobutane thymine dimers (TT dimers), the major DNA lesions induced by UV irradiation. Loss of human Poleta leads to xeroderma pigmentosum variant syndrome, clearly indicating that Poleta plays a vital role in preventing skin cancer caused by exposure to sunlight. To further examine Poleta functions and the mechanisms that regulate this important protein, Poleta complexes were purified from HeLa cells over-expressing epitope-tagged Poleta, and polypeptides associated with Poleta, including Rad18, Rad6 and Rev1, were identified by a combination of mass spectrometry and Western blot analysis. The chromatin-bound fractions of cells subjected to UV irradiation, S phase synchronization, or S phase arrest were specifically enriched in such complexes. These results suggest that arrested replication forks strengthen interactions among Poleta, Rad18/Rad6 and Rev1, consistent with the requirement for effective TLS by Poleta at sites of DNA lesions.


Relationship between laser Doppler signals and anatomy during deep brain stimulation electrode implantation toward the ventral intermediate nucleus and subthalamic nucleus.
Deep brain stimulation (DBS) requires precise and safe navigation to the chosen target. Optical measurements allow monitoring of gray-white tissue boundaries (total light intensity [TLI]) and microvascular blood flow during stereotactic procedures. To establish the link between TLI/blood flow and anatomy along trajectories toward the ventral intermediate nucleus (Vim) and subthalamic nucleus (STN). Stereotactic laser Doppler measurements were obtained with millimeter precision from the cortex toward the Vim (n = 13) and STN (n = 9). Optical trajectories of TLI and blood flow were created and compared with anatomy by superimposing the Schaltenbrandt-Wahren atlas on the patients' pre- and postoperative images. Measurements were divided into anatomic subgroups and compared statistically. Typical TLI trajectories with well-defined anatomic regions could be identified for the Vim and STN. TLI was significantly lower (P < .001) and microvascular blood flow significantly higher (P = .01) in the Vim targets. Of 1285 sites, 38 showed blood flow peaks, 27 of them along the Vim trajectories. High blood flow was more common close to the sulci and in the vicinity of the caudate/putamen. Along 1 Vim trajectory, a slight bleeding was suspected during insertion of the probe and confirmed with postoperative computed tomography. Laser Doppler is useful for intraoperative guidance during DBS implantation because simultaneous measurement of tissue grayness and microvascular blood flow can be done along the trajectory with millimeter precision. Typical but different TLI trajectories were found for the Vim and STN.


Inflammation marker and risk of pancreatic cancer: a nested case-control study within the EPIC cohort.
Established risk factors for pancreatic cancer include smoking, long-standing diabetes, high body fatness, and chronic pancreatitis, all of which can be characterised by aspects of inflammatory processes. However, prospective studies investigating the relation between inflammatory markers and pancreatic cancer risk are scarce. We conducted a nested case-control study within the European Prospective Investigation into Cancer and Nutrition, measuring prediagnostic blood levels of C-reactive protein (CRP), interleukin-6 (IL-6), and soluble receptors of tumour necrosis factor-α (sTNF-R1, R2) in 455 pancreatic cancer cases and 455 matched controls. Odds ratios (ORs) were estimated using conditional logistic regression models. None of the inflammatory markers were significantly associated with risk of pancreatic cancer overall, although a borderline significant association was observed for higher circulating sTNF-R2 (crude OR=1.52 (95% confidence interval (CI) 0.97-2.39), highest vs lowest quartile). In women, however, higher sTNF-R1 levels were significantly associated with risk of pancreatic cancer (crude OR=1.97 (95% CI 1.02-3.79)). For sTNF-R2, risk associations seemed to be stronger for diabetic individuals and those with a higher BMI. Prospectively, CRP and IL-6 do not seem to have a role in our study with respect to risk of pancreatic cancer, whereas sTNF-R1 seemed to be a risk factor in women and sTNF-R2 might be a mediator in the risk relationship between overweight and diabetes with pancreatic cancer. Further large prospective studies are needed to clarify the role of proinflammatory proteins and cytokines in the pathogenesis of exocrine pancreatic cancer.


Prefrontal Dynamics Associated with Efficient Detours and Shortcuts: A Combined Functional Magnetic Resonance Imaging and Magnetoencenphalography Study.
Central to the concept of the "cognitive map" is that it confers behavioral flexibility, allowing animals to take efficient detours, exploit shortcuts, and avoid alluring, but unhelpful, paths. The neural underpinnings of such naturalistic and flexible behavior remain unclear. In two neuroimaging experiments, we tested human participants on their ability to navigate to a set of goal locations in a virtual desert island riven by lava, which occasionally spread to block selected paths (necessitating detours) or receded to open new paths (affording real shortcuts or false shortcuts to be avoided). Detours activated a network of frontal regions compared with shortcuts. Activity in the right dorsolateral PFC specifically increased when participants encountered tempting false shortcuts that led along suboptimal paths that needed to be differentiated from real shortcuts. We also report modulation in event-related fields and theta power in these situations, providing insight to the temporal evolution of response to encountering detours and shortcuts. These results help inform current models as to how the brain supports navigation and planning in dynamic environments.


SU-D-218-02: 4D-MRI Based on Body Area (BA) Surrogate and Sagittal Image Acquisition.
4D-MRI based on body area (BA) surrogate using axial image acquisition has been demonstrated. Since respiratory motion mostly occurs in the superior-inferior (SI) direction, it is expected that sagittal acquisition may provide more robust and accurate breathing signal than axial acquisition. The aim of this study was to investigate the feasibility of extracting breathing signals from sagittal images using BA surrogate and its application in 4D-MRI. 7 human subjects were imaged continuously in a single (n=5) or multiple (n=2) sagittal planes using a steady-state precession sequence. Imaging parameters were: TR/TE, 3.7ms/1.21ms; Matrix, 256×166; FOV, 350×300mm; flip angle, 52°; slice thickness, 5mm; frame rate: ∼3 frames/s. Imaging time per slice is 2 minutes for single slice acquisition and ∼10 seconds for multi-slice acquisition. Breathing signals were generated for all subjects by tracking the change of BA. The multi-slice sagittal acquisition was performed on a MRI- compatible motion phantom with a cylindrical gel target and was simulated on a 4D digital human phantom. Breathing signals were extracted from the sagittal images using the BA surrogate. Respiratory phases were calculated. 4D-MRI of both phantoms were retrospectively reconstructed based on the respiratory phases. Breathing signals extracted from both single slice and multi-slice sagittal acquisitions showed stable and well- characterized patterns. 4D-MRI of the physical phantom showed clear sinusoidal motion of the gel target in all three planes with minimal artifacts. Simulated '4D-MRI' of the 4D digital phantom matched well with original images: the mean absolute difference in motion amplitude of the 'tumor' was 0.4±0.3mm. Small artifacts of discontinuity were observed in the SI direction in certain phases. It is feasible to extract breathing signals from sagittal images for 4D-MRI application. Further investigation is needed to test whether sagittal acquisition is more robust and accurate than axial acquisition for breathing signal extraction.


Four ways blue foods can help achieve food system ambitions across nations.
Blue foods, sourced in aquatic environments, are important for the economies, livelihoods, nutritional security and cultures of people in many nations. They are often nutrient rich1, generate lower emissions and impacts on land and water than many terrestrial meats2, and contribute to the health3, wellbeing and livelihoods of many rural communities4. The Blue Food Assessment recently evaluated nutritional, environmental, economic and justice dimensions of blue foods globally. Here we integrate these findings and translate them into four policy objectives to help realize the contributions that blue foods can make to national food systems around the world: ensuring supplies of critical nutrients, providing healthy alternatives to terrestrial meat, reducing dietary environmental footprints and safeguarding blue food contributions to nutrition, just economies and livelihoods under a changing climate. To account for how context-specific environmental, socio-economic and cultural aspects affect this contribution, we assess the relevance of each policy objective for individual countries, and examine associated co-benefits and trade-offs at national and international scales. We find that in many African and South American nations, facilitating consumption of culturally relevant blue food, especially among nutritionally vulnerable population segments, could address vitamin B12 and omega-3 deficiencies. Meanwhile, in many global North nations, cardiovascular disease rates and large greenhouse gas footprints from ruminant meat intake could be lowered through moderate consumption of seafood with low environmental impact. The analytical framework we provide also identifies countries with high future risk, for whom climate adaptation of blue food systems will be particularly important. Overall the framework helps decision makers to assess the blue food policy objectives most relevant to their geographies, and to compare and contrast the benefits and trade-offs associated with pursuing these objectives.


Ureteric embolization with stainless-steel coils for managing refractory lower urinary tract fistula: a 12-year experience.
To report our 12-year experience with radiological treatment (ureteric embolization) for refractory urinary fistula, as malignancy, radiation therapy, and/or chronic inflammation increase the risk of lower urinary tract fistula after surgical urinary diversion, which can lead to significant morbidity, and for patients who are not surgical candidates permanent nephrostomy drainage and ureteric embolization offer an alternative form of urinary diversion. We retrospectively reviewed patients who had ureteric occlusion for refractory urinary fistula at our institution between 1993 and 2005. Stainless-steel coils, with or without gelatine sponge, were placed antegradely through a percutaneous nephrostomy tract. Patients were then managed by long-term nephrostomy drainage until death or definitive reconstructive surgery. In all, 29 patients (23 women and six men; mean age 59 years, sd 16) were identified who had urinary fistulae that were refractory to nephrostomy drainage alone. One patient had a history of severe perineal trauma and the remaining 28 had a history of cancer. Seventeen fistulae occurred in the setting of previous surgery, 20 patients had received adjunctive pelvic irradiation and 11 had had chemotherapy. In all, 52 ureters were embolized; occlusion was successful in all cases, with complete or near-complete (<1 pad/day) dryness within 3 days. No repeat embolization was required and there were no significant complications. Two patients were lost to follow-up. Three patients had definitive urinary diversion surgery and currently are well. One patient is alive and living with nephrostomy tubes; 23 patients have died. Ureteric embolization is a viable option for managing complex lower urinary tract fistulae in patients with a poor performance status. It can be used as definitive management in patients with a limited life-expectancy or as a temporary measure in those for whom another management plan is anticipated.


Thin laser light sheet microscope for microbial oceanography.
Despite a growing need, oceanographers are limited by existing technological constrains and are unable to observe aquatic microbes in their natural setting. In order to provide a simple and easy to implement solution for such studies, a new Thin Light Sheet Microscope (TLSM) has been developed. The TLSM utilizes a well-defined sheet of laser light, which has a narrow (23 micron) axial dimension over a 1 mm x 1 mm field of view. This light sheet is positioned precisely within the depth of field of the microscope's objective lens. The technique thus utilizes conventional microscope optics but replaces the illumination system. The advantages of the TLSM are two-fold: First, it concentrates light only where excitation is needed, thus maximizing the efficiency of the illumination source. Secondly, the TLSM maximizes image sharpness while at the same time minimizing the level of background noise. Particles that are not located within the objective's depth of field are not illuminated and therefore do not contribute to an out-of-focus image. Images from a prototype system that used SYBR Green I fluorescence stain in order to localize single bacteria are reported. The bacteria were in a relatively large and undisturbed volume of 4ml, which contained natural seawater. The TLSM can be used for fresh water studies of bacteria with no modification. The microscope permits the observation of interactions at the microscale and has potential to yield insights into how microbes structure pelagic ecosystems.


Evaluation of antimicrobial activity of ceftaroline against Clostridium difficile and propensity to induce C. difficile infection in an in vitro human gut model.
To examine the effects of exposure to ceftaroline or ceftriaxone on the epidemic Clostridium difficile strain PCR ribotype 027 and the indigenous gut microflora in an in vitro human gut model. Additionally, the MICs of ceftriaxone and ceftaroline for 60 C. difficile isolates were determined. Two triple-stage chemostat gut models were primed with human faeces and exposed to ceftaroline (10 mg/L, twice daily, 7 days) or ceftriaxone (150 mg/L, once daily, 7 days). Populations of indigenous gut microorganisms, C. difficile total viable counts, spore counts, cytotoxin titres and antimicrobial concentrations were monitored throughout. MICs were determined by a standard agar incorporation method. In the gut model, both ceftaroline and ceftriaxone induced C. difficile spore germination, proliferation and toxin production, although germination occurred 5 days later in the ceftaroline-exposed model. Toxin detection was sustained until the end of the experimental period in both models. No active antimicrobial was detected in vessel 3 of either model, although inhibitory effects on microflora populations were observed. Ceftaroline was ∼8-fold more active against C. difficile than ceftriaxone (geometric mean MICs, 3.38 versus 28.18 mg/L; MIC90s, 4 versus 64 mg/L; and MIC ranges, 0.125-16 versus 8-128 mg/L). Ceftaroline, like ceftriaxone, can induce simulated C. difficile infection in a human gut model. However, low in vivo gut concentrations of ceftaroline and increased activity against C. difficile in comparison with ceftriaxone mean that the true propensity of this novel cephalosporin to induce C. difficile infection remains unclear.


Assessment of phytoremediation potencial of Allium cepa L. in raw sewage treatment.
Whereas the effects of the substances found in domestic sewage on live organisms is important to evaluate the use of plants to remove pollutants from the environment. The objective of this study was to assess the phytoremediation activity of Allium cepa L. (onion) roots exposed to raw sewage, as well as the acute toxic activity of this effluent for the bioindicators A. cepa, through a cytotoxicity test, and Artemia salina L., through a mortality/immobility test. The physicochemical assessments of the sewage were conducted in two scenarios: immediately after collection and after being in contact with onion roots (phytoremediation) for 24 hours. The physicochemical data indicate there was a reduction in nitrogen and phosphorus levels and in biochemical oxygen demand in sewage treated. The results from the cytotoxicity test with A. cepa indicated a reduction in the mitotic cell divisions of the onions treated with the raw sewage. The mortality/immobility test with A. salina indicated that the concentrations with 50 and 100% of raw sewage induced the mortality of the nauplii. Thus, the data suggest new studies that seek greater efficiency, efficacy and viability of onion phytoremediation.


Thrombocytopenia associated with intravenous ciprofloxacin.
A variety of disease states, disorders, hereditary conditions, environmental toxins, and drugs may cause thrombocytopenia. Fluoroquinolones, however, are not thought to be common offenders. We report the case of a 72-year-old woman who was receiving intravenous ciprofloxacin for a urinary tract infection and developed thrombocytopenia during her hospital stay. Her platelet count dropped from 147 x 10(3)/mm3 on admission to as low as 21 x 10(3)/mm3 . On discontinuation of the drug, her platelet counts began to return to normal. After discharge, the patient continued to improve clinically. Four days after discharge, her platelet count was 197 x 10(3)/mm3 . In the primary literature, we found two case reports on thrombocytopenia associated with ciprofloxacin and one case report with alatrofloxacin. In addition, six additional case reports were found in non-English journals that describe fluoroquinolone-associated thrombocytopenia. Clinicians should be aware of the possible relationship between thrombocytopenia and fluoroquinolones, and platelet counts should monitored accordingly.


Interactions between Fusarium verticillioides, Ustilago maydis, and Zea mays: an endophyte, a pathogen, and their shared plant host.
Highly diverse communities of microbial symbionts occupy eukaryotic organisms, including plants. While many well-studied symbionts may be characterized as either parasites or as mutualists, the prevalent but cryptic endophytic fungi are less easily qualified because they do not cause observable symptoms of their presence within their host. Here, we investigate the interactions of an endophytic fungus, Fusarium verticillioides with a pathogen, Ustilago maydis, as they occur within maize (Zea mays). We used experimental inoculations to evaluate metabolic mechanisms by which these three organisms might interact. We assessed the impacts of fungal-fungal interactions on endophyte and pathogen growth within the plant, and on plant growth. We find that F. verticillioides modulates the growth of U. maydis and thus decreases the pathogen's aggressiveness toward the plant. With co-inoculation of the endophyte with the pathogen, plant growth is similar to that which would be gained without the pathogen present. However, the endophyte may also break down plant compounds that limit U. maydis growth, and obtains a growth benefit from the presence of the pathogen. Thus, an endophyte such as F. verticillioides may function as both a defensive mutualist and a parasite, and express nutritional modes that depend on ecological context.


High degree of fluoroquinolone resistance among pulmonary tuberculosis patients in New Delhi, India.
: The fluoroquinolones (FQs) group of antibiotics is the backbone drugs for the management of drug-resistant tuberculosis (TB). In routine clinical practice, drug susceptibility testing (DST) for FQs is not performed, and the patients are empirically treated. A limited information exists regarding FQs resistance among pulmonary TB cases. The present study was conducted to determine the FQs resistance among drug sensitive and drug-resistant pulmonary TB patients in a tertiary care centre in north India. : A total of 1619 sputum/smear-positive specimens of pulmonary TB patients were subjected to DST for first-line drugs (FLDs) and second-line drugs. In addition, FQs DST was also performed using automated Mycobacterial Growth Indicator Tube-960 liquid culture technique. The immuno-chromatographic assay was performed to distinguish Mycobacterium tuberculosis complex (MTBC) from non-MTBC. : Mycobacterium tuberculosis (Mtb) was isolated in 1499 sputum specimens; 1099 culture specimens were sensitive to FLDs, 249 grew as multidrug-resistant (MDR) Mtb and the remaining 151 isolates revealed any drug resistance to FLDs. While FQs monoresistance among the FLD sensitive isolates was 3.1 per cent (35/1099), 27.3 per cent (68/249) among MDR Mtb isolates had additional FQs resistance. : FQs resistance among drug sensitive and MDR Mtb isolates was high in Delhi, India. Based on these findings, it is recommended that the DST for FQs should be routinely performed to avoid further amplification of drug resistance.


Interactive Visualization and On-Demand Processing of Large Volume Data: A Fully GPU-Based Out-of-Core Approach.
In a wide range of scientific fields, 3D datasets production capabilities have widely evolved in recent years, especially with the rapid increase in their sizes. As a result, many large-scale applications, including visualization or processing, have become challenging to address. A solution to this issue lies in providing out-of-core algorithms specifically designed to handle datasets significantly larger than memory. In this article, we present a new approach that extends the broad interactive addressing principles already established in the field of out-of-core volume rendering on GPUs to allow on-demand processing during the visualization stage. We propose a pipeline designed to manage data as regular 3D grids regardless of the underlying application. It relies on a caching approach with a virtual memory addressing system coupled to an efficient parallel management on GPU to provide efficient access to data in interactive time. It allows any visualization or processing application to leverage the flexibility of its structure by managing multi-modality datasets. Furthermore, we show that our system delivers good performance on a single standard PC with low memory budget on the GPU.


Reverse transcription real-time PCR assays for detection and quantification of Borna disease virus in diseased hosts.
Borna disease is a severe, immunopathological disorder of the central nervous system caused by the infection with the Borna disease virus (BDV). The detection of BDV in diseased animals, mainly sheep and horses, is achieved by histological, immunohistochemical and serological approaches and/or PCR-based technologies. In the present study, reverse transcription, real-time PCR assays were established for the detection of BDV in the brain tissue from sheep and horses, using loci for the p40 (nucleoprotein) and the p24 (phosphoprotein) genes. The PCRs were equally specific and sensitive, detecting 10 target molecules per reaction and one BDV-infected cell among 10(6) non-infected cells. In tissues from BDV-diseased sheep and horses, the p24 target was detected at higher abundance than for p40. Therefore, the p24 test is suggested to be of higher value in the diagnostic laboratory. However, both assays should be useful for addressing questions in pathogenesis and for detecting BDV reservoirs in endemic areas.


Isolation and characterization of olfactory ecto-mesenchymal stem cells from eight mammalian genera.
Stem cell-based therapies are an attractive option to promote regeneration and repair defective tissues and organs. Thanks to their multipotency, high proliferation rate and the lack of major ethical limitations, "olfactory ecto-mesenchymal stem cells" (OE-MSCs) have been described as a promising candidate to treat a variety of damaged tissues. Easily accessible in the nasal cavity of most mammals, these cells are highly suitable for autologous cell-based therapies and do not face issues associated with other stem cells. However, their clinical use in humans and animals is limited due to a lack of preclinical studies on autologous transplantation and because no well-established methods currently exist to cultivate these cells. Here we evaluated the feasibility of collecting, purifying and amplifying OE-MSCs from different mammalian genera with the goal of promoting their interest in veterinary regenerative medicine. Biopsies of olfactory mucosa from eight mammalian genera (mouse, rat, rabbit, sheep, dog, horse, gray mouse lemur and macaque) were collected, using techniques derived from those previously used in humans and rats. The possibility of amplifying these cells and their stemness features and differentiation capability were then evaluated. Biopsies were successfully performed on olfactory mucosa without requiring the sacrifice of the donor animal, except mice. Cell populations were rapidly generated from olfactory mucosa explants. These cells displayed similar key features of their human counterparts: a fibroblastic morphology, a robust expression of nestin, an ability to form spheres and similar expression of surface markers (CD44, CD73). Moreover, most of them also exhibited high proliferation rates and clonogenicity with genus-specific properties. Finally, OE-MSCs also showed the ability to differentiate into mesodermal lineages. This article describes for the first time how millions of OE-MSCs can be quickly and easily obtained from different mammalian genera through protocols that are well-suited for autologous transplantations. Moreover, their multipotency makes them relevant to evaluate therapeutic application in a wide variety of tissue injury models. This study paves the way for the development of new fundamental and clinical studies based on OE-MSCs transplantation and suggests their interest in veterinary medicine.


Short lingual frenum in infants, children and adolescents. Part 1: Breastfeeding and gastroesophageal reflux disease improvement after tethered oral tissues release.
This study aimed to determine the impact of laser surgical tongue-tie, lip-tie, buccal tie release on breastfeeding and Gastroesophageal Reflux Disease (GERD) in a prospective cohort study conducted from June 2019 to June 2020 in a private general dental practice. Preoperative, one-week and one-month postoperative surveys were completed, consisting of Visual Analogue Scale (VAS) for nipple pain severity, Breastfeeding Self-Efficacy Scale Short Form (BSES-SF), and the Revised Infant Gastroesophageal Reflux Questionnaire (I-GERQ-R). All study participants were breastfeeding dyads (0-12 weeks of age) with untreated ankyloglossia and/or tethered maxillary/buccal frena. The laser surgery was completed using 2 different near- infrared diode lasers with 300µm diameter fibre: a 980 nm wavelength diode laser (Lasotronix Smart Pro, Piaseczno Poland) was used at 4.0 W, gated with 100 µs t/on and 100 µs t/off, and a 1470 nm wavelength diode laser (Pioon S1, Wuhan Pioon Tech Co Ltd., Wuhan, China), used at 3.5W, gated with 50 ms t/on and 50 ms t/off. Statistically significant improvement was noted in VAS, I-GERQ-R and BSES-SF comparing preoperative scores to both one-week and one-month scores. The study had 132 breastfeeding dyads enrolled. Posterior tongue-tie was noted in 71% of this cohort. This study confirms the need for functional assessment of tongue and lip movement for this significantly affected cohort. Laser surgical release (frenotomy) of tongue-tie, lip-tie, buccal-tie resulted in significant improvement in breastfeeding outcomes. These improvements (VAS, I-GERQ-R and BSES-SF) in breastfeeding outcomes were found for cohorts of the classically recognised anterior tongue-tie and the less obvious (without functional assessment) submucosal tongue-tie were found.


Appropriate intervention strategies for weight gain induced by olanzapine: a randomized controlled study.
Weight gain induced by antipsychotics is the second most frequently given reason for noncompliance with pharmacologic therapy; excessive sedative effects rank first, with extrapyramidal side effects ranking third. Frequently, weight gain leads to inconsistent pharmacologic treatment; this exposes patients to the risk of recurrent symptoms. In fact, one of the key contributors to good clinical outcomes in schizophrenic patients is compliance with pharmacologic treatment. The goals of this study were to evaluate weight gain in a group of patients treated with olanzapine, diet modifications, and moderate physical activity and to compare the findings with those from a second group of patients who were given only olanzapine treatment. For 8 wk, investigators followed 2 groups of patients suffering from schizophrenia and hypomania in bipolar disorder, according to the nosographic criteria of The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). The first group (A) of 18 patients (9 female, 9 male) affected by manic episodes in bipolar disorder received olanzapine (10-20 mg/d), jogged lightly for 30 min 3 times a week, and complied with a diet that consisted of 500 kcal/d less than usual. The second group (B) of 10 patients (4 female, 6 male) with schizophrenia received only olanzapine (10-20 mg/d). All patients from both groups were weighed at the beginning of the observation period and weekly thereafter for 2 mo. After 2 mo of observation, group A showed a mean weight gain of 1.47 kg, whereas group B exhibited a mean weight gain of 3.5 kg; the difference between the 2 groups was almost 2 kg (P<.005). Group A showed a statistically significant reduction in weight gain compared with group B, clearly demonstrating the effectiveness of moderate physical activity and diet therapy in reducing weight gain in atypical antipsychotic treatment. Therefore, patient weight and body mass index must be monitored during the first weeks of antipsychotic treatment, with the goals of avoiding significant weight gain and treatment interruption.


Between-monitor differences in step counts are related to body size: implications for objective physical activity measurement.
The quantification of the relationships between walking and health requires that walking is measured accurately. We correlated different measures of step accumulation to body size, overall physical activity level, and glucose regulation. Participants were 25 men and 25 women American Indians without diabetes (Age: 20-34 years) in Phoenix, Arizona, USA. We assessed steps/day during 7 days of free living, simultaneously with three different monitors (Accusplit-AX120, MTI-ActiGraph, and Dynastream-AMP). We assessed total physical activity during free-living with doubly labeled water combined with resting metabolic rate measured by expired gas indirect calorimetry. Glucose tolerance was determined during an oral glucose tolerance test. Based on observed counts in the laboratory, the AMP was the most accurate device, followed by the MTI and the AX120, respectively. The estimated energy cost of 1000 steps per day was lower in the AX120 than the MTI or AMP. The correlation between AX120-assessed steps/day and waist circumference was significantly higher than the correlation between AMP steps and waist circumference. The difference in steps per day between the AX120 and both the AMP and the MTI were significantly related to waist circumference. Between-monitor differences in step counts influence the observed relationship between walking and obesity-related traits.


On the effects of cycloheximide on cell motility and polarisation in Dictyostelium discoideum.
Cycloheximide is a protein synthesis inhibitor that acts specifically on the 60S subunit of eukaryotic ribosomes. It has previously been shown that a short incubation of Dictyostelium discoideum amoebae in cycloheximide eliminates fluid phase endocytosis. We found that treatment with cycloheximide also causes the amoebae to retract their pseudopodia, round up and cease movement. Furthermore, fluid phase endocytosis, phagocytosis and capping cease in the presence of 2 mM cycloheximide, although membrane uptake, as measured using FM1-43, is unaffected. In the presence of cycloheximide, aggregation-competent amoebae sensitive to cAMP, although round, can still localise CRAC, ABP120, PI3K and actin polymerisation in response to a micropipette filled with cAMP. The behaviour of wild-type amoebae in the presence of cycloheximide is surprisingly similar to that of amoebae having a temperature-sensitive version of NSF at the restrictive temperature. Our results may suggest that, upon cycloheximide treatment, either a labile protein required for polarised membrane recycling is lost, or a control mechanism linking protein synthesis to membrane recycling is activated.


Inhibitory effect of six green tea catechins and caffeine on the growth of four selected human tumor cell lines.
Green tea is an aqueous infusion of dried unfermented leaves of Camellia sinensis (family Theaceae) from which numerous biological activities have been reported including antimutagenic, antibacterial, hypocholesterolemic, antioxidant, antitumor and cancer preventive activities. From the aqueous-alcoholic extract of green tea leaves, six compounds (+)-gallocatechin (GC), (-)-epicatechin (EC), (-)-epigallocatechin (EGC), (-)-epicatechin gallate (ECG), (-)-epigallocatechin gallate (EGCG) and caffeine, were isolated and purified. Together with (+)-catechin, these compounds were tested against each of four human tumor cells lines (MCF-7 breast carcinoma, HT-29 colon carcinoma, A-427 lung carcinoma and UACC-375 melanoma). The three most potent green tea components against all four tumor cell lines were EGCG, GC and EGC. EGCG was the most potent of the seven green tea components against three out of the four cell lines (i.e. MCF-7 breast cancer, HT-29 colon cancer and UACC-375 melanoma). On the basis of these extensive in vitro studies, it would be of considerable interest to evaluate all three of these components in comparative preclinical in vivo animal tumor model systems before final decisions are made concerning which of these potential chemopreventive drugs should be taken into broad clinical trials.


cFOS expression in the prefrontal cortex correlates with altered cerebral metabolism in developing germ-free mice.
The microbiota plays a critical role in modulating various aspects of host physiology, particularly through the microbiota-gut-brain (MGB) axis. However, the mechanisms that transduce and affect gut-to-brain communication are still not well understood. Recent studies have demonstrated that dysbiosis of the microbiome is associated with anxiety and depressive symptoms, which are common complications of metabolic syndrome. Germ-free (GF) animal models offer a valuable tool for studying the causal effects of microbiota on the host. We employed gene expression and nuclear magnetic resonance (NMR)-based metabolomic techniques to investigate the relationships between brain plasticity and immune gene expression, peripheral immunity, and cerebral and liver metabolism in GF and specific pathogen-free (SPF) mice. Our principal findings revealed that brain acetate (p = 0.012) was significantly reduced in GF relative to SPF mice, whereas glutamate (p = 0.0013), glutamine (p = 0.0006), and N-acetyl aspartate (p = 0.0046) metabolites were increased. Notably, cFOS mRNA expression, which was significantly decreased in the prefrontal cortex of GF mice relative to SPF mice (p = 0.044), correlated with the abundance of a number of key brain metabolites altered by the GF phenotype, including glutamate and glutamine. These results highlight the connection between the GF phenotype, altered brain metabolism, and immediate-early gene expression. The study provides insight into potential mechanisms by which microbiota can regulate neurotransmission through modulation of the host's brain and liver metabolome, which may have implications for stress-related psychiatric disorders such as anxiety.


Improving the management of family psychosocial problems at low-income children's well-child care visits: the WE CARE Project.
Our goal was to evaluate the feasibility and impact of an intervention on the management of family psychosocial topics at well-child care visits at a medical home for low-income children. A randomized, controlled trial of a 10-item self-report psychosocial screening instrument was conducted at an urban hospital-based pediatric clinic. Pediatric residents and parents were randomly assigned to either the intervention or control group. During a 12-week period, parents of children aged 2 months to 10 years presenting for a well-child care visit were enrolled. The intervention components included provider training, administration of the family psychosocial screening tool to parents before the visit, and provider access to a resource book that contained community resources. Parent outcomes were obtained from postvisit and 1-month interviews, and from medical chart review. Provider outcomes were obtained from a self-administered questionnaire collected after the study. Two hundred parents and 45 residents were enrolled. Compared with the control group, parents in the intervention group discussed a significantly greater number of family psychosocial topics (2.9 vs 1.8) with their resident provider and had fewer unmet desires for discussion (0.46 vs 1.41). More parents in the intervention group received at least 1 referral (51.0% vs 11.6%), most often for employment (21.9%), graduate equivalent degree programs (15.3%), and smoking-cessation classes (14.6%). After controlling for child age, Medicaid status, race, educational status, and food stamps, intervention parents at 1 month had greater odds of having contacted a community resource. The majority of residents in the intervention group reported that the survey instrument did not slow the visit; 54% reported that it added <2 minutes to the visit. Brief family psychosocial screening is feasible in pediatric practice. Screening and provider training may lead to greater discussion of topics and contact of community family support resources by parents.


Interannual variability in the North Atlantic Ocean carbon sink.
The North Atlantic is believed to represent the largest ocean sink for atmospheric carbon dioxide in the Northern Hemisphere, yet little is known about its temporal variability. We report an 18-year time series of upper-ocean inorganic carbon observations from the northwestern subtropical North Atlantic near Bermuda that indicates substantial variability in this sink. We deduce that the carbon variability at this site is largely driven by variations in winter mixed-layer depths and by sea surface temperature anomalies. Because these variations tend to occur in a basinwide coordinated pattern associated with the North Atlantic Oscillation, it is plausible that the entire North Atlantic Ocean may vary in concert, resulting in a variability of the strength of the North Atlantic carbon sink of about +/-0.3 petagrams of carbon per year (1 petagram = 10(15) grams) or nearly +/-50%. This extrapolation is supported by basin-wide estimates from atmospheric carbon dioxide inversions.


A worldwide analysis of beta-defensin copy number variation suggests recent selection of a high-expressing DEFB103 gene copy in East Asia.
Beta-defensins are a family of multifunctional genes with roles in defense against pathogens, reproduction, and pigmentation. In humans, six beta-defensin genes are clustered in a repeated region which is copy-number variable (CNV) as a block, with a diploid copy number between 1 and 12. The role in host defense makes the evolutionary history of this CNV particularly interesting, because morbidity due to infectious disease is likely to have been an important selective force in human evolution, and to have varied between geographical locations. Here, we show CNV of the beta-defensin region in chimpanzees, and identify a beta-defensin block in the human lineage that contains rapidly evolving noncoding regulatory sequences. We also show that variation at one of these rapidly evolving sequences affects expression levels and cytokine responsiveness of DEFB103, a key inhibitor of influenza virus fusion at the cell surface. A worldwide analysis of beta-defensin CNV in 67 populations shows an unusually high frequency of high-DEFB103-expressing copies in East Asia, the geographical origin of historical and modern influenza epidemics, possibly as a result of selection for increased resistance to influenza in this region.


Low levels of vitamin D in neuromyelitis optica spectrum disorder: association with disease disability.
Patients with autoimmune disorders often have low levels of 25-hydroxyvitamin D [25(OH)D3], which correlates with disability or disease activity. Vitamin D may play a role in neuromyelitis optica (NMO) or NMO spectrum disorder (NMOSD), as an important factor involved in immunological pathways. We investigated the relationship between vitamin D levels and disease related disability and clinical activity in patients with NMOSD. Blood samples from 51 patients with NMOSD who were positive for anti-aquaporin4-antibody (AQP4-ab) and 204 healthy controls were collected for 25(OH)D3 measurement. Clinical parameters, including expanded disability status scale (EDSS) score, annualized relapse rate (ARR) and time of blood sampling relative to attack, were determined in patients with NMOSD. We found that 25(OH)D3 levels were significantly lower in patients with NMOSD compared to healthy controls. There was no difference between 25(OH)D3 levels in blood samples taken at relapse or remission, and no association between 25(OH)D3 levels and ARR, but there was an inverse correlation between 25(OH)D3 levels and EDSS scores in patients with NMOSD. It remains to be determined whether low vitamin D levels predispose to NMO and/or modify disease severity, or are secondary to neurological disability. In either case the results could also be of relevance to other neurological diseases such as multiple sclerosis as well as NMO.


Molecular Pathways: The Balance between Cancer and the Immune System Challenges the Therapeutic Specificity of Targeting Nuclear Factor-κB Signaling for Cancer Treatment.
The NF-κB signaling pathway is a complex network linking extracellular stimuli to cell survival and proliferation. Cytoplasmic signaling to activate NF-κB can occur as part of the DNA damage response or in response to a large variety of activators, including viruses, inflammation, and cell death. NF-κB transcription factors play a fundamental role in tumorigenesis and are implicated in the origination and propagation of both hematologic and solid tumor types, including melanoma, breast, prostate, ovarian, pancreatic, colon, lung, and thyroid cancers. On the other hand, NF-κB signaling is key to immune function and is likely necessary for antitumor immunity. This presents a dilemma when designing therapeutic approaches to target NF-κB. There is growing interest in identifying novel modulators to inhibit NF-κB activity as impeding different steps of the NF-κB pathway has potential to slow tumor growth, progression, and resistance to chemotherapy. Despite significant advances in our understanding of this pathway, our ability to effectively clinically block key targets for cancer therapy remains limited due to on-target effects in normal tissues. Tumor specificity is critical to developing therapeutic strategies targeting this antiapoptotic signaling pathway to maintain antitumor immune surveillance when applying such therapy to patients. Clin Cancer Res; 22(17); 4302-8. ©2016 AACR.


Identification of Targetable ALK Rearrangements in Pancreatic Ductal Adenocarcinoma.
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers, with a 5-year survival of 8%. Current therapeutic regimens are largely ineffective and underscore the need for novel treatment strategies. Chromosomal rearrangements involving the anaplastic lymphoma kinase (ALK) gene have been identified in several neoplasms. In addition, ALK protein inhibitors have proven efficacy in patients with ALK-rearranged tumors. However, ALK translocations in PDAC have not been described. Through comprehensive genomic profiling of 3,170 PDACs, we identified 5 cases (0.16%) that harbored an ALK fusion gene: an exon 6 EML4-exon 20 ALK translocation (n=3), an exon 13 EML4-exon 20 ALK translocation (n=1), and an exon 3 STRN-exon 20 ALK translocation (n=1). Among the most prevalent PDAC-related genes, activating KRAS mutations were absent in all 5 cases, who were <50 years of age. Among patients aged <50 years in our study cohort, ALK translocations constituted 1.3% of PDACs. Four of 5 patients were treated with an ALK inhibitor, and 3 of these patients demonstrated stable disease, radiographic response, and/or normalization of serum CA 19-9. Although rare, ALK fusions occur in PDAC, and screening for ALK rearrangements should be considered in young patients with PDAC.


N,N-dimethylformamide: evidence of carcinogenicity from national representative cohort study in South Korea.
Objective There is limited epidemiological evidence of carcinogenicity on exposure of N,N-dimethylformamide (DMF). This study aimed to identify the possible association between cancer mortality and DMF exposure. Methods A cohort of 11 953 workers exposed to DMF between 1 January 2000 and 31 December 2004 was studied. A urinary metabolite of DMF, N-methylformamide level (UNMFL), was used for exposure assessment. This cohort was matched with the mortality data of the Korean National Statistical Office and followed up for cancer mortality between 2000 and 2011. Standardized mortality ratios (SMR) of the DMF-exposed workers with reference to Korean men were calculated. Adjusted hazard ratios (HRadj; also controlling for age, other carcinogen exposure including hepatitis B and C) were calculated for the workers categorized in three exposure groups with reference to workers with no exposure. Results The HRadj of overall cancer mortality were significantly increased in workers with 7.5-<15 mg/L [HRadj 2.72, 95% confidence interval (CI) 1.09-6.81] and ≥15 mg/L (HRadj 2.41, 95% CI 1.03-5.66) compared with non-exposed workers. Hepatocellular carcinoma mortality (HRadj 3.73, 95% CI 1.05-13.24) of workers with ≥15 mg/L and lung cancer mortality (HRadj 14.36, 95% CI 1.41-146.86) in workers with 7.5-<15 mg/L were significantly increased. Conclusions Workers with high DMF exposure showed increased mortalities for overall, liver, and lung cancer. Our results suggest that DMF causes cancer, especially hepatocellular carcinoma, which is in agreement with earlier studies on liver cancer in animal experiments.


Problems with the assessment of dietary fat in prostate cancer studies.
The authors conducted a detailed review of studies on the association between prostate cancer and total dietary fat along with specific fatty acids. Overall, the 29 studies reporting actual dietary fat levels in grams of fat were heterogeneous, suggesting that pooling of the relative risks may be inappropriate. Heterogeneity was also seen by study design. More specifically, although the pooled estimate for prostate cancer and an increase of 45 g in total fat consumption per day was small (relative risk = 1.2), heterogeneity between studies was large, and the association was not supported by specific fatty acids. The strongest association was found among the five extremely inconsistent studies of alpha-linolenic fatty acid. The associations with advanced prostate cancer were more homogeneous and suggest a relation with total and saturated fat but none with specific fatty acids. This review highlights the inconsistent way in which total dietary fat and specific fatty acids have been measured and reported across epidemiologic studies of prostate cancer. The heterogeneity between studies was large, possibly because of the variation in the dietary instruments used and the corresponding databases (nondifferential misclassification), recall bias, differing case definitions, residual confounding, or potential selection bias in different studies.


Mechanism of tRNA-mediated +1 ribosomal frameshifting.
Accurate translation of the genetic code is critical to ensure expression of proteins with correct amino acid sequences. Certain tRNAs can cause a shift out of frame (i.e., frameshifting) due to imbalances in tRNA concentrations, lack of tRNA modifications or insertions or deletions in tRNAs (called frameshift suppressors). Here, we determined the structural basis for how frameshift-suppressor tRNASufA6 (a derivative of tRNAPro) reprograms the mRNA frame to translate a 4-nt codon when bound to the bacterial ribosome. After decoding at the aminoacyl (A) site, the crystal structure of the anticodon stem-loop of tRNASufA6 bound in the peptidyl (P) site reveals ASL conformational changes that allow for recoding into the +1 mRNA frame. Furthermore, a crystal structure of full-length tRNASufA6 programmed in the P site shows extensive conformational rearrangements of the 30S head and body domains similar to what is observed in a translocation intermediate state containing elongation factor G (EF-G). The 30S movement positions tRNASufA6 toward the 30S exit (E) site disrupting key 16S rRNA-mRNA interactions that typically define the mRNA frame. In summary, this tRNA-induced 30S domain change in the absence of EF-G causes the ribosome to lose its grip on the mRNA and uncouples the canonical forward movement of the tRNAs during elongation.


Biochemical investigation of the formation of three-dimensional networks from DNA-grafted large silica particles.
DNA is used to rationally build up networks of silica nanoparticles (SiNPs) based on the molecular recognition properties of complementary sequences. Network self-assembly is controlled from DNA covalently grafted at the surface of chemically modified SiNPs. Two strategies are compared, where grafted DNA sequences are designed in a three-strand system using noncomplementary sequences and an extra DNA linker, or in a two-strand approach for direct hybridization. In this paper, both systems are compared in terms of DNA hybridization stability, network size, and three-dimensional organization using a combination of dynamic light scattering and electron microscopy. The observed differences are discussed in terms of hybridization interactions between DNA sequences in particle-free systems through fluorescence, circular dichroism, and UV spectroscopy techniques.


Palliative Care Interventions for Surgical Patients: A Systematic Review.
Inpatient palliative care improves symptom management and patient satisfaction with care and reduces hospital costs in seriously ill patients. However, the role of palliative care in the treatment of patients undergoing surgery (surgical patients) remains poorly defined. To characterize the content, design, and results of interventions to improve access to palliative care or the quality of palliative care for surgical patients. This systematic review was conducted according to PRIMSA guidelines. Articles were identified through searches of PubMed, PsycINFO, EMBASE, and CINAHL as well as manual review of references. Eligible articles included experimental, quasi-experimental, and observational studies published in English from January 1, 1994, through October 31, 2014, in which patient outcomes of palliative care interventions for adult surgical patients were reported. Data on the study setting, design, intervention, participants, and results were extracted from the final study set and analyzed from December 22, 2014, to February 7, 2015. A total of 3838 abstracts were identified and screened by 2 reviewers, 77 articles were reviewed in full text, and 25 articles (22 unique interventions involving 8575 unique patients) met the study criteria. Interrater agreement was good (κ = 0.78). Nine single-institution retrospective cohort studies, 7 single-institution prospective cohort studies, 7 single-institution randomized clinical studies, and 2 multicenter randomized clinical studies were included. Nineteen of the 23 single-site studies were performed at academic hospitals. Given the heterogeneity of study methods and measures, meta-analysis was not possible. Preoperative decision-making interventions were associated with decreased mortality in 4 studies. Three studies reported improved quality of communication; 4, improved symptom management; and 7, decreased use of health care resources and decreased cost. However, many studies were small, performed in academic settings, and methodologically flawed and did not measure clinically meaningful outcomes. The sparse evidence regarding interventions to introduce or improve palliative care for surgical patients is further limited by methodologic flaws. Rigorous evaluations of standardized palliative care interventions measuring meaningful patient outcomes are needed.


Analysis of nonreciprocal mode propagation in magneto-optic rib-waveguide structures with the spectral-index method.
Passive linear nonreciprocal devices, such as isolators or circulators, require gyrotropic media. If there is a contribution to the dielectric permittivity tensor of odd order in the magnetization, the modes propagate differently in the forward and the backward directions. We investigate dielectric waveguides that are formed by a rib of rectangular cross section on top of a planar structure. The rib or planar structure may consist of layers, each of which may be gyrotropic. We extend the spectral-index method for calculating differences between forward- and backward-propagation constants. A new design for an efficient nonreciprocal phase shifter is proposed.


Pancreatic islet expression studies and polymorphic DNA markers in the genes encoding hepatocyte nuclear factor-3alpha, -3beta, -3gamma, -4gamma, and -6.
The genes encoding the functionally related hepatocyte nuclear factors HNF-1alpha and HNF-4alpha play a critical role in normal pancreatic beta-cell function. Mutations in these liver-enriched transcription factors result in two forms of early-onset type 2 diabetes (maturity-onset diabetes of the young [MODY]), MODY3 and MODY1, which are characterized by impaired glucose-stimulated insulin secretion, early disease onset, and autosomal dominant inheritance. The transcriptional hierarchy of HNFs suggests that other proteins of the regulatory cascade might be responsible for other forms of MODY and/or late-onset type 2 diabetes. In this study, we show that HNF-3alpha, -3beta, -3gamma, -4gamma, and -6 are expressed in pancreatic beta-cells. We report the identification and characterization of simple tandem repeat DNA polymorphisms in the genes encoding HNF-3alpha, -3beta, -3gamma, -4gamma, and -6 and the mapping of HNF-6 to chromosome bands 15q21.1-21.2 by fluorescence in situ hybridization. These markers will be useful to study the role of genetic variation in these genes in the pathogenesis of type 2 diabetes.


[The diagnosis of neurodegenerative disorders based on clinical and pathological findings using an MRI approach].
Diffusion tensor imaging and voxel based morphometry are efficient in the diagnosis of neurodegenerative disorders, however, these technologies are available at a limited number of facilities. Thus, conventional MRI remains important in the diagnosis of neurodegenerative disorders. Dorsolateral putaminal hyperintensity (DPH) and hot cross bun sign discriminate Parkinson's disease from multiple system atrophy (MSA). However, differences in magnetic field strength and sequence affect the sensitivity of DPH, and mild DPH may be observed in normal elderly subjects. Patients with progressive supranuclear palsy (PSP) presenting Richardson's syndrome show midbrain tegmentum atrophy, but Parkinsonian PSP (PSP-P) and pure akinesia with gait freezing, which are other phenotypes of PSP, may not show especially during early course of illness. In patients with corticobasal degeneration (CBD), asymmetrical cerebral atrophy corresponding with corticobasal syndrome (CBS) may be a characteristic finding. However, at autopsy, CBS patients presenting asymmetrical cerebral atrophy have CBD as the underlying pathology in approximately 50% of PSP patients. The sensitivity and specificity of MRI for the diagnosis of MSA, PSP, and CBD is based generally on clinical diagnostic criteria. Diagnosis based on MRI has limitations, and, therefore, we should reconsider our diagnoses, particularly during the early course of illness.


Welfarism versus extra-welfarism: can the choice of economic evaluation approach impact on the adoption decisions recommended by economic evaluation studies?
A long-running debate surrounds the equivalence of the welfarist and extra-welfarist approaches to economic evaluation. There is a growing belief that the extra-welfarist approach may not necessarily provide all the information that decisionmakers require in certain contexts, e.g. evaluation of complex interventions. As the number of these interventions being evaluated increases, it is crucial that the most appropriate economic evaluation approach is used to enable decisionmakers to be confident in their adoption decisions. We conducted a literature review to evaluate the potential for the choice of economic evaluation approach to impact on the adoption decisions recommended by economic evaluation studies. We found that for every five studies applying both approaches, one shows limited or no concordance in economic evaluation results: the different approaches suggest conflicting adoption decisions, and there is no pattern to which approach provides the most convincing adoption evidence. Only one study in ten indicates which results will best inform adoption decisions. We conclude that the choice of approach can significantly impact on the adoption decisions recommended by economic evaluation studies, with conflicting results creating confusion over whether or not interventions provide good value for money. Health economists rarely provide sufficient guidance to decisionmakers to alleviate this confusion.


Management of airway compromise following thyroid cyst hemorrhage after thrombolytic therapy.
The risk of hemorrhage after therapeutic administration of tissue plasminogen activator (tPA) is well known. Cases of postadministration hemorrhage have been reported within many organ systems. We present a case of a 62-year-old female with undiagnosed thyroid goiter who received tPA for acute ischemic stroke and developed acute airway compromise. The surgical airway response team was called due to inability to ventilate or intubate. An incision into the mass during attempted tracheotomy released colloid and blood, decompressing the airway and facilitating ventilation and intubation. Hemithyroidectomy for mass removal was delayed for 3 days to allow normalization of post-tPA coagulopathy.