Berberine-induced apoptosis in human breast cancer cells is mediated by reactive oxygen species generation and mitochondrial-related apoptotic pathway.
Berberine has drawn extensive attention toward their wide range of biochemical and pharmacological effects, including antineoplastic effect in recent years, but the precise mechanisms remain unclear. Treatment of human breast cancer cells (MCF-7 and MDA-MB-231 cells) with berberine induced inhibition of cell viability in concentration- and time-dependent manner irrespective of their estrogen receptor (ER) expression. Hoechst33342 staining confirmed berberine induced breast cancer cell apoptosis in time-dependent manner. Because apoptosis induction is considered to be a crucial strategy for cancer prevention and therapy, berberine may be an effective chemotherapeutic agent against breast cancer. To explore the precise mechanism, berberine-induced oxidative stress and mitochondrial-related apoptotic pathway in human breast cancer cells were investigated in this study. In both MCF-7 and MDA-MB-231 cells, berberine increased the production of reactive oxygen species (ROS), which activated the pro-apoptotic JNK signaling. Phosphorylated JNK triggered mitochondria membrane potential (ΔΨm) depolarization and downregulation expression of anti-apoptotic protein Bcl-2 concomitant with the upregulation expression of pro-apoptotic protein Bax. Downregulation of anti-apoptotic Bcl-2 family protein in parallel with loss of ΔΨm, leading to increased the release of cytochrome c and apoptosis-inducing factor (AIF) from mitochondria, and eventually triggered the caspase-dependent and caspase-independent apoptosis. Taken together, our study reveled that berberine exerted an antitumor activity in breast cancer cells by reactive oxygen species generation and mitochondrial-related apoptotic pathway. These finding provide an insight into the potential of berberine for breast cancer therapy.


Development of human serine protease-based therapeutics targeting Fn14 and identification of Fn14 as a new target overexpressed in TNBC.
The cytokine TWEAK and its receptor, Fn14, have emerged as potentially valuable targets for cancer therapy. Granzyme B (GrB)-containing Fn14-targeted constructs were generated containing either the Fn14 ligand TWEAK (GrB-TWEAK) or an anti-Fn14 humanized single-chain antibody (GrB-Fc-IT4) as the targeting moieties. Both constructs showed high affinity and selective cytotoxicity against a panel of Fn14-expressing human tumor cells including triple-negative breast cancer (TNBC) lines. Cellular expression of the GrB inhibitor PI-9 in target cells had no impact on the cytotoxic effect of either construct. Cellular expression of MDR1 showed no cross-resistance to the fusion constructs. GrB-TWEAK and GrB-Fc-IT4 activated intracellular caspase cascades and cytochrome c-related proapoptotic pathways consistent with the known intracellular functions of GrB in target cells. Treatment of mice bearing established HT-29 xenografts with GrB-TWEAK showed significant tumor growth inhibition compared with vehicle alone (P < 0.05). Both GrB-TWEAK and GrB-Fc-IT4 displayed significant tumor growth inhibition when administered to mice bearing orthotopic MDA-MB-231 (TNBC) tumor xenografts. The Cancer Genome Atlas analysis revealed that Fn14 mRNA expression was significantly higher in TNBC and in HER2-positive disease (P < 0.0001) compared with hormone receptor-positive breast cancer, and in basal-like 2 tumors (P = 0.01) compared with other TNBC molecular subtypes. IHC analysis of a 101 patient TNBC tumor microarray showed that 55 of 101 (54%) of tumors stained positive for Fn14, suggesting that this may be an excellent potential target for precision therapeutic approaches. Targeting Fn14 using fully human, GrB-containing fusion constructs may form the basis for a new class of novel, potent, and highly effective constructs for targeted therapeutic applications.


Glenohumeral joint capsular tissue tension loading correlates moderately with shear wave elastography: a cadaveric investigation.
The purpose of this study was to investigate changes in the mechanical properties of capsular tissue using shear wave elastography (SWE) and a durometer under various tensile loads, and to explore the reliability and correlation of SWE and durometer measurements to evaluate whether SWE technology could be used to assess tissue changes during capsule tensile loading. The inferior glenohumeral joint capsule was harvested from 10 fresh human cadaveric specimens. Tensile loading was applied to the capsular tissue using 1-, 3-, 5-, and 8-kg weights. Blinded investigators measured tissue stiffness and hardness during loading using SWE and a durometer, respectively. Intraobserver reliability was established for SWE and durometer measurements using intraclass correlation coefficients (ICCs). The Pearson product-moment correlation was used to assess the associations between SWE and durometer measurements. The ICC3,5 for durometer measurements was 0.90 (95% confidence interval [CI], 0.79 to 0.96; P<0.001) and 0.95 (95% CI, 0.88 to 0.98; P<0.001) for SWE measurements. The Pearson correlation coefficient values for 1-, 3-, and 5-kg weights were 0.56 (P=0.095), 0.36 (P=0.313), and -0.56 (P=0.089), respectively. When the 1- and 3-kg weights were combined, the ICC3,5 was 0.72 (P<0.001), and it was 0.62 (P<0.001) when the 1-, 3-, and 5-kg weights were combined. The 8-kg measurements were severely limited due to SWE measurement saturation of the tissue samples. This study suggests that SWE is reliable for measuring capsular tissue stiffness changes in vitro at lower loads (1 and 3 kg) and provides a baseline for the non-invasive evaluation of effects of joint loading and mobilization on capsular tissues in vivo.


High-resolution ultrasound and magnetic resonance imaging to document tissue repair after prolotherapy: a report of 3 cases.
High-resolution ultrasound imaging of musculoskeletal tissue is increasing in popularity because of patient tolerability, low cost, ability to visualize tissue in real-time motion, and superior resolution of highly organized tissue such as a tendon. Prolotherapy, defined as the injection of growth factors or growth factor production stimulants to grow normal cells or tissue, has been a controversial procedure for decades; it is currently gaining in popularity among physiatrists and other musculoskeletal physicians. This report describes imaging of tendons, ligaments, and medial meniscus disease (from trauma or degeneration). Although these tissues have been poorly responsive to nonsurgical treatment, it is proposed that tissue growth and repair after prolotherapy in these structures can be documented with ultrasound and confirmed with magnetic resonance imaging. Directions for future research application are discussed.


Functional Connectivity of the Pedunculopontine Nucleus and Surrounding Region in Parkinson's Disease.
Deep brain stimulation of the pedunculopontine nucleus and surrounding region (PPNR) is a novel treatment strategy for gait freezing in Parkinson's disease (PD). However, clinical results have been variable, in part because of the paucity of functional information that might help guide selection of the optimal surgical target. In this study, we use simultaneous magnetoencephalography and local field recordings from the PPNR in seven PD patients, to characterize functional connectivity with distant brain areas at rest. The PPNR was preferentially coupled to brainstem and cingulate regions in the alpha frequency (8-12 Hz) band and to the medial motor strip and neighboring areas in the beta (18-33 Hz) band. The distribution of coupling also depended on the vertical distance of the electrode from the pontomesencephalic line: most effects being greatest in the middle PPNR, which may correspond to the caudal pars dissipata of the pedunculopontine nucleus. These observations confirm the crucial position of the PPNR as a functional node between cortical areas such as the cingulate/ medial motor strip and other brainstem nuclei, particularly in the dorsal pons. In particular they suggest a special role for the middle PPNR as this has the greatest functional connectivity with other brain regions.


PaPro1 and IDC4, Two Genes Controlling Stationary Phase, Sexual Development and Cell Degeneration in Podospora anserina.
Filamentous fungi frequently undergo bistable phenotypic switches. Crippled Growth of Podospora anserina is one such bistable switch, which seems to rely upon the mis-activation of a self-regulated PaMpk1 MAP kinase regulatory pathway. Here, we identify two new partners of this pathway: PaPro1, a transcription factor orthologous to Sordaria macrospora pro1 and Neurospora crassa ADV-1, and IDC4, a protein with an AIM24 domain. Both PaPro1 and IDC4 regulate stationary phase features, as described for the other actors of the PaMpk1 signaling pathway. However, PaPro1 is also involved in the control of fertilization by activating the transcription of the HMG8 and the mating type transcription factors, as well as the sexual pheromones and receptor genes. The roles of two components of the STRIPAK complex were also investigated by inactivating their encoding genes: PaPro22 and PaPro45. The mutants of these genes were found to have the same phenotypes as PaPro1 and IDC4 mutants as well as additional phenotypes including slow growth, abnormally shaped hyphae, pigment accumulation and blockage of the zygotic tissue development, indicating that the STRIPAK complex regulates, in addition to the PaMpk1 one, other pathways in P. anserina. Overall, the mutants of these four genes confirm the model by which Crippled Growth is due to the abnormal activation of the PaMpk1 MAP kinase cascade.


Analysis of pedestrian accident costs in Sudan using the willingness-to-pay method.
The willingness-to-pay (WTP) with contingent valuation (CV) method has been proven to be a valid tool for the valuation of non-market goods or socio-economic costs of road traffic accidents among communities in developed and developing countries. Research on accident costing tends to estimate the value of statistical life (VOSL) for all road users by providing a principle for the evaluation of road safety interventions in cost-benefit analysis. As in many other developing countries, the economic loss of traffic accidents in Sudan is noticeable; however, analytical research to estimate the magnitude and impact of that loss is lacking. Reports have shown that pedestrians account for more than 40% of the total number of fatalities. In this study, the WTP-CV approach was used to determine the amount of money that pedestrians in Sudan are willing to pay to reduce the risk of their own death. The impact of the socioeconomic factors, risk levels, and walking behaviors of pedestrians on their WTP for fatality risk reduction was also evaluated. Data were collected from two cities-Khartoum and Nyala-using a survey questionnaire that included 1400 respondents. The WTP-CV Payment Card Questionnaire was designed to ensure that Sudan pedestrians can easily determine the amount of money that would be required to reduce the fatality risk from a pedestrian-related accident. The analysis results show that the estimated VOSL for Sudanese pedestrians ranges from US$0.019 to US$0.101 million. In addition, the willingness-to-pay by Sudanese pedestrians to reduce their fatality risk tends to increase with age, household income, educational level, safety perception, and average time spent on social activities with family and community.


Ubiquitinylation of Ig beta dictates the endocytic fate of the B cell antigen receptor.
In both infection and autoimmunity, the development of high-affinity Abs and memory requires B cells to efficiently capture and process Ags for presentation to cognate T cells. Although a great deal is known about how Ags are processed, the molecular mechanisms by which the BCR captures Ag for processing are still obscure. In this study, we demonstrate that the Ig beta component of the BCR is diubiquitinylated and that this is dependent on the E3 ligase Itch. Itch-/- B lymphocytes manifest both a defect in ligand-induced BCR internalization and endocytic trafficking to late endosomal Ag-processing compartments. In contrast, analysis of ubiquitinylation-defective receptors demonstrated that the attachment of ubiquitins to Ig beta is required for endosomal sorting and for the presentation of Ag to T cells, yet, ubiquitinylation is dispensable for receptor internalization. Membrane-bound Ig mu was not detectably ubiquitinylated nor were the conserved lysines in the mu cytosolic tail required for trafficking to late endosomes. These results demonstrate that ubiquitinylation of a singular substrate, Ig beta, is required for a specific receptor trafficking event. However, they also reveal that E3 ligases play a broader role in multiple processes that determine the fate of Ag-engaged BCR complexes.


"Provide care for everyone please": engaging community leaders as sexual and reproductive health advocates in North and South Kivu, Democratic Republic of the Congo.
Inadequate infrastructure, security threats from ongoing armed conflict, and conservative socio-cultural and gender norms that favour large families and patriarchal power structures contribute to poor sexual and reproductive health (SRH) outcomes in North and South Kivu provinces, Democratic Republic of the Congo (DRC). In order to expand contraceptive and post-abortion care (PAC) access in North and South Kivu, CARE, the International Rescue Committee and Save the Children provided technical support to the Ministry of Health and health facilities in these regions. Partners acknowledged that community leaders, given their power to influence local customs, could play a critical role as agents of change in addressing inequitable gender norms, stigma surrounding SRH service utilization, and topics traditionally considered taboo within Congolese society. As such, partners actively engaged with community leaders through a variety of activities such as community mapping exercises, values clarification and transformation (VCAT) activities, situational analyses, and education. This manuscript presents findings from 12 key informant interviews (KIIs) with male political and non-political community leaders conducted in six rural health zones of North and South Kivu, DRC. Transcripts were analysed thematically to explore community leaders' perceptions of their role in addressing the issue of unintended pregnancy in their communities. While community leaders in this study expressed overall positive impressions of contraception and strong support for ensuring access to PAC services following spontaneous and induced abortions, the vast majority held negative beliefs concerning women who had induced abortion. Contrasting with their professed opposition to induced abortion, leaders' commitment to mediating interpersonal conflict arising between community members and women who had abortions was overwhelming. Results from this study suggest that when thoughtfully engaged by health interventions, community leaders can be empowered to become advocates for SRH. While study participants were strong supporters of contraception and PAC, they expressed negative perceptions of induced abortion. Given the hypothesized link between the presence of induced abortion stigma and care-avoidance behavior, further engagement and values clarification exercises with leaders must be integrated into community mobilization and engagement activities in order to increase PAC utilization.


A comparison of wandering behavior in nursing homes and assisted living facilities.
Wandering, a challenging behavior associated with dementia, affects many residents of long-term care facilities and can result in elopement, injury, and death. Most studies of wandering have taken place in nursing homes (NH). Expansion of the long-term care sector over the last 2 decades has resulted in a surge in options such as assisted living facilities (ALF). This study compared wandering behavior of residents (N = 108) in 21 long-term care facilities (15 NH, 6 ALF). Staff used the Revised Algase Wandering Scale-Nursing Home Version (RAWS-NH) to quantify wandering. While there were some differences in demographic variables (i.e., race, motor ability) between NH and ALF participants, no significant differences were found in either RAWS-NH overall or any of the 6 subscale scores. This suggests that the expression of wandering is similar in long-term care residents across all dimensions of the RAWS-NH regardless of facility type. Findings are of concern for those involved in the safe management and protection of residents at risk for wandering, particularly in long-term care facilities with underregulated staffing and training requirements.


The tumor suppressor gene, lethal(2)giant larvae (1(2)g1), is required for cell shape change of epithelial cells during Drosophila development.
Inactivation of the lethal(2)giant larvae (l(2)gl) gene results in malignant transformation of imaginal disc cells and neuroblasts of the larval brain in Drosophila. Subcellular localization of the l(2)gl gene product, P127, and its biochemical characterization have indicated that it participates in the formation of the cytoskeletal network. In this paper, genetic and phenotypic analyses of a temperature-sensitive mutation (l(2)glts3) that behaves as a hypomorphic allele at restrictive temperature are presented. In experimentally overaged larvae obtained by using mutants in the production of ecdysone, the l(2)glts3 mutation displays a tumorous potential. This temperature-sensitive allele of the l(2)gl gene has been used to describe the primary function of the gene before tumor progression. A reduced contribution of both maternal and zygotic activities in l(2)glts3 homozygous mutant embryos blocks embryogenesis at the end of germ-band retraction. The mutant embryos are consequently affected in dorsal closure and head involution and show a hypertrophy of the midgut. These phenotypes are accompanied by an arrest of the cell shape changes normally occurring in lateral epidermis and in epithelial midgut cells. l(2)gl activity is also necessary for larval fife and the critical period falls within the third instar larval stage. Finally, l(2)gl activity is required during oogenesis and mutations in the gene disorganize egg chambers and cause abnormalities in the shape of follicle cells, which are eventually internalized within the egg chamber. These results together with the tumoral phenotype of epithelial imaginal disc cells strongly suggest that the l(2)gl product is required in vivo in different types of epithelial cells to control their shape during development.


ANI-1: an extensible neural network potential with DFT accuracy at force field computational cost.
Deep learning is revolutionizing many areas of science and technology, especially image, text, and speech recognition. In this paper, we demonstrate how a deep neural network (NN) trained on quantum mechanical (QM) DFT calculations can learn an accurate and transferable potential for organic molecules. We introduce ANAKIN-ME (Accurate NeurAl networK engINe for Molecular Energies) or ANI for short. ANI is a new method designed with the intent of developing transferable neural network potentials that utilize a highly-modified version of the Behler and Parrinello symmetry functions to build single-atom atomic environment vectors (AEV) as a molecular representation. AEVs provide the ability to train neural networks to data that spans both configurational and conformational space, a feat not previously accomplished on this scale. We utilized ANI to build a potential called ANI-1, which was trained on a subset of the GDB databases with up to 8 heavy atoms in order to predict total energies for organic molecules containing four atom types: H, C, N, and O. To obtain an accelerated but physically relevant sampling of molecular potential surfaces, we also proposed a Normal Mode Sampling (NMS) method for generating molecular conformations. Through a series of case studies, we show that ANI-1 is chemically accurate compared to reference DFT calculations on much larger molecular systems (up to 54 atoms) than those included in the training data set.


Effect of phage on the infectivity of Vibrio cholerae and emergence of genetic variants.
Seasonal epidemics of cholera in Bangladesh are self-limited in nature, presumably due to phage predation of the causative Vibrio cholerae during the late stage of an epidemic, when cholera patients excrete large quantities of phage in their stools. To further understand the mechanisms involved, we studied the effect of phage on the infectivity and survival of V. cholerae shed in stools. The 50% infectious dose of stool vibrios in infant mice was approximately 10-fold higher when the stools contained a phage (1.8 x 10(3) to 5.7 x 10(6) PFU/ml) than when stools did not contain a detectable phage. In competition assays in mice using a reference strain and phage-negative cholera stools, the infectivity of biofilm-like clumped cells was 3.9- to 115.9-fold higher than that of the corresponding planktonic cells. However, the difference in infectivity of these two cell populations in phage-positive stools was significantly less than that in phage-negative stools (P = 0.0006). Coculture of a phage and V. cholerae or dilutions of phage-positive cholera stools in nutrient medium, but not in environmental water, caused rapid emergence of phage-resistant derivatives of the bacteria, and these derivatives lost their O1 antigen. In cholera stools and in intestinal contents of mice prechallenged with a mixture of V. cholerae and phage, the bacteria remained completely phage susceptible, suggesting that the intestinal environment did not favor the emergence of phage-resistant derivatives that lost the O1 antigen. Our results indicate that phages lead to the collapse of epidemics by modulating the required infectious dose of the bacteria. Furthermore, the dominance of phage-resistant variants due to the bactericidal selective mechanism occurs rarely in natural settings, and the emerging variants are thus unable to sustain the ongoing epidemic.


The relationship between social support, depression and treatment for depression in people with multiple sclerosis.
Studies have been fairly consistent in finding a relationship between social support and depression. However, little is known about the relationship between depression and social support in the context of treatment for depression. This study examined the effects of treatment for depression on social support among patients with multiple sclerosis (MS). Sixty-three moderately depressed MS patients received 16 weeks of cognitive behaviour therapy (CBT), supportive expressive group psychotherapy (SEGP) or sertraline. Depression was measured using the Beck Depression Inventory and social support was measured using Arizona Social Support Interview Schedule. Treatment for depression was associated with significant increases in perceived social support, utilized social support and satisfaction with support, as well as reduction in need for emotional support. There were no significant changes in structural support or need for physical support. There were also no differences in change in social support across treatments. All changes in social support were fully explained by depression. Improvements in utilized social support and satisfaction with social support were fully mediated by improvements in depression. Baseline depression predicted improvements in perceived support and need for emotional support. These findings suggest that improvements in social support among MS patients during treatment for depression can be explained by depression. However, different domains of social support may be differentially sensitive to changes in depression.


Using Contextual Learning to Improve Diagnostic Accuracy: Application in Breast Cancer Screening.
Clinicians need to routinely make management decisions about patients who are at risk for a disease such as breast cancer. This paper presents a novel clinical decision support tool that is capable of helping physicians make diagnostic decisions. We apply this support system to improve the specificity of breast cancer screening and diagnosis. The system utilizes clinical context (e.g., demographics, medical history) to minimize the false positive rates while avoiding false negatives. An online contextual learning algorithm is used to update the diagnostic strategy presented to the physicians over time. We analytically evaluate the diagnostic performance loss of the proposed algorithm, in which the true patient distribution is not known and needs to be learned, as compared with the optimal strategy where all information is assumed known, and prove that the false positive rate of the proposed learning algorithm asymptotically converges to the optimum. In addition, our algorithm also has the important merit that it can provide individualized confidence estimates about the accuracy of the diagnosis recommendation. Moreover, the relevancy of contextual features is assessed, enabling the approach to identify specific contextual features that provide the most value of information in reducing diagnostic errors. Experiments were conducted using patient data collected at a large academic medical center. Our proposed approach outperforms the current clinical practice by 36% in terms of false positive rate given a 2% false negative rate.


Neural correlates of conflict control on facial expressions with a flanker paradigm.
Conflict control is an important cognitive control ability and it is also crucial for human beings to execute conflict control on affective information. To address the neural correlates of cognitive control on affective conflicts, the present study recorded event-related potentials (ERPs) during a revised Eriksen Flanker Task. Participants were required to indicate the valence of the central target expression while ignoring the flanker expressions in the affective congruent condition, affective incongruent condition and neutral condition (target expressions flanked by scramble blocks). Behavioral results manifested that participants exhibited faster response speed in identifying neutral target face when it was flanked by neutral distractors than by happy distractors. Electrophysiological results showed that happy target expression induced larger N2 amplitude when flanked by sad distractors than by happy distractors and scramble blocks during the conflict monitoring processing. During the attentional control processing, happy target expression induced faster P3 response when it was flanked by happy distractors than by sad distractors, and sad target expression evoked larger P3 amplitude when it was flanked by happy distractors comparing with sad distractors. Taken together, the current findings of temporal dynamic of brain activity during cognitive control on affective conflicts shed light on the essential relationship between cognitive control and affective information processing.


Stem cell mechanical behaviour modelling: substrate's curvature influence during adhesion.
Recent experiments hint that adherent cells are sensitive to their substrate curvature. It is already well known that cells behaviour can be regulated by the mechanical properties of their environment. However, no mechanisms have been established regarding the influence of cell-scale curvature of the substrate. Using a numerical cell model, based on tensegrity structures theory and the non-smooth contact dynamics method, we propose to investigate the mechanical state of adherent cells on concave and convex hemispheres. Our mechanical cell model features a geometrical description of intracellular components, including the cell membrane, the focal adhesions, the cytoskeleton filament networks, the stress fibres, the microtubules, the nucleus membrane and the nucleoskeleton. The cell model has enabled us to analyse the evolution of the mechanical behaviour of intracellular components with varying curvature radii and with the removal of part of these components. We have observed the influence of the convexity of the substrate on the cell shape, the cytoskeletal force networks as well as on the nucleus strains. The more convex the substrate, the more tensed the stress fibres and the cell membrane, the more compressed the cytosol and the microtubules, leading to a stiffer cell. Furthermore, the more concave the substrate, the more stable and rounder the nucleus. These findings achieved using a verified virtual testing methodology, in particular regarding the nucleus stability, might be of significant importance with respect to the division and differentiation of mesenchymal stem cells. These results can also bring some hindsights on cell migration on curved substrates.


Molecular identification of larvae of a tetraphyllidean tapeworm (Platyhelminthes: Eucestoda) in a razor clam as an alternative intermediate host in the life cycle of Acanthobothrium brevissime.
Dwarf razor clams (Ensis minor) in the Gulf of Mexico are known to be infected with plerocercoid larvae of a tetraphyllidean tapeworm. Here, we show that these larvae live unencysted in the intestinal lumen of the clam. Morphologically, the larvae are similar to (although significantly larger than) tapeworm larvae previously described living in the gut of amphioxus (Branchiostoma floridae) from the same habitat. Sequence data from the D2 region of the 28S rDNA from clam-infecting larvae were identical to the sequence of Acanthobothrium brevissime isolated as larvae from amphioxus and as adults from a stingray (Dasyatis say). The sequence data leave little doubt that the dwarf razor clam and the amphioxus are alternative intermediate hosts in the life cycle of A. brevissime.


Womens' beliefs and practices regarding food restrictions during pregnancy and lactation: a hospital based study.
Maternal diet is an important determinant of outcomes of pregnancy. Malnutrition during pregnancy and its consequences maximally affect the health and long-term outcomes of the population. Low birth weight accounts for almost 30% of all births; with maternal malnutrition as a dominant risk factor. This study aims to investigate the existing beliefs and practices regarding food restrictions during pregnancy and lactation and also to assess whether there is any relationship with education level of the respondent and their beliefs and practices. A cross-sectional survey was conducted at Community Health Center (CHC) of The Aga Khan University Hospital, Karachi from July-September 2000. Four hundred adult female respondents, who came to the outpatient services as a patient or as an attendant, were interviewed after taking verbal consent. A self administered pre-coded and pre-tested questionnaire was filled by the respondent. More than three fourths of respondents were literate. Twelve percent believed in restricting some food item during pregnancy and about 25% believed the same during lactation. No statistically significant association was found between belief about food restriction during pregnancy or during lactation and education level of the respondent. Undue food restrictions during pregnancy and lactation do exist in our culture. To assess the true picture we need to conduct larger studies in the community. The information obtained from the studies will help us in addressing these issues for improvement of nutritional knowledge and dietary practices and to avoid undue food restrictions.


Cells Control BIN1-Mediated Membrane Tubulation by Altering the Membrane Charge.
The Bridging integrator 1 (BIN1)/Amphiphysin/Rvs (BAR) protein family is an essential part of the cell's machinery to bend membranes. BIN1 is a muscle-enriched BAR protein with an established role in muscle development and skeletal myopathies. Here, we demonstrate that BIN1, on its own, is able to form complex interconnected tubular systems in vitro, reminiscent of t-tubule system in muscle cells. We further describe how BIN1's electrostatic interactions regulate membrane bending: the ratio of negatively charged lipids in the bilayer altered membrane bending and binding properties of BIN1 and so did the manipulation of BIN1's surface charge. We show that the electrostatically mediated BIN1 membrane binding depended on the membrane curvature-it was less affected in liposomes with high curvature. Curiously, BIN1 membrane binding and bending was diminished in cells where the membrane's charge was experimentally reduced. Membrane bending was also reduced in BIN1 mutants where negative or positive charges in the BAR domain have been eliminated. This phenotype, characteristic of BIN1 mutants linked to myopathies, was rescued when the membrane charge was made more negative. The latter findings also show that cells can control tubulation at their membranes by simply altering the membrane charge and through it, the recruitment of BAR proteins and their interaction partners (e.g. dynamin).


Molecular magnetic resonance imaging of brain-immune interactions.
Although the blood-brain barrier (BBB) was thought to protect the brain from the effects of the immune system, immune cells can nevertheless migrate from the blood to the brain, either as a cause or as a consequence of central nervous system (CNS) diseases, thus contributing to their evolution and outcome. Accordingly, as the interface between the CNS and the peripheral immune system, the BBB is critical during neuroinflammatory processes. In particular, endothelial cells are involved in the brain response to systemic or local inflammatory stimuli by regulating the cellular movement between the circulation and the brain parenchyma. While neuropathological conditions differ in etiology and in the way in which the inflammatory response is mounted and resolved, cellular mechanisms of neuroinflammation are probably similar. Accordingly, neuroinflammation is a hallmark and a decisive player of many CNS diseases. Thus, molecular magnetic resonance imaging (MRI) of inflammatory processes is a central theme of research in several neurological disorders focusing on a set of molecules expressed by endothelial cells, such as adhesion molecules (VCAM-1, ICAM-1, P-selectin, E-selectin, …), which emerge as therapeutic targets and biomarkers for neurological diseases. In this review, we will present the most recent advances in the field of preclinical molecular MRI. Moreover, we will discuss the possible translation of molecular MRI to the clinical setting with a particular emphasis on myeloperoxidase imaging, autologous cell tracking, and targeted iron oxide particles (USPIO, MPIO).


Diagnosing ocular surface squamous neoplasia in East Africa: case-control study of clinical and in vivo confocal microscopy assessment.
To examine the reliability of clinical examination and in vivo confocal microscopy (IVCM) in distinguishing ocular surface squamous neoplasia (OSSN) from benign conjunctival lesions. Case-control study. Sixty individuals with conjunctival lesions (OSSN and benign) and 60 age-matched controls with normal conjunctiva presenting to Kilimanjaro Christian Medical Centre, Moshi, Tanzania. Participants were examined and photographed, and IVCM was performed. Patients with conjunctival lesions were offered excisional biopsy with histopathology and a human immunodeficiency virus (HIV) test. The IVCM images were read masked to the clinical appearance and pathology results. Images were graded for several specific features and given an overall categorization (normal, benign, or malignant). A group of 8 ophthalmologists were shown photographs of conjunctival lesions and asked to independently classify as OSSN or benign. Comparison of the histopathology diagnosis with the clinical and IVCM diagnosis. Fifty-two cases underwent excisional biopsy with histopathology; 34 were on the OSSN spectrum, 17 were benign, and 1 was lymphoma. The cases and controls had comparable demographic profiles. Human immunodeficiency syndrome infection was more common in OSSN compared with benign cases (58.8% vs. 5.6%; odds ratio, 24.3, 95% confidence interval [CI], 2.8-204; P = 0.003). Clinically, OSSN lesions more frequently exhibited feeder vessels and tended to have more leukoplakia and a gelatinous appearance. Overall, the ophthalmologists showed moderate agreement with the histology result (average kappa = 0.51; 95% CI, 0.36-0.64). The masked grading of IVCM images reliably distinguished normal conjunctiva. However, IVCM was unable to reliably distinguish between benign lesions and OSSN because of an overlap in their appearance (kappa = 0.44; 95% CI, 0.32-0.57). No single feature was significantly more frequent in OSSN compared with benign lesions. The sensitivity and specificity of IVCM for distinguishing OSSN from benign conjunctival lesions were 38.5% and 66.7%, respectively. In East Africa, conjunctival pathology is relatively common and can present significant diagnostic challenges for the clinician. In this study, neither clinical examination nor IVCM was found to reliably distinguish OSSN from benign conjunctival pathology because of an overlap in the features of these groups. Therefore, IVCM cannot currently replace histopathology, and management decisions should continue to rely on careful clinical assessment supported by histopathology as indicated.


The quick motor function test: a new tool to rate clinical severity and motor function in Pompe patients.
Pompe disease is a lysosomal storage disorder characterized by progressive muscle weakness. With the emergence of new treatment options, psychometrically robust outcome measures are needed to monitor patients' clinical status. We constructed a motor function test that is easy and quick to use. The Quick Motor Function Test (QMFT) was constructed on the basis of the clinical expertise of several physicians involved in the care of Pompe patients; the Gross Motor Function Measure and the IPA/Erasmus MC Pompe survey. The test comprises 16 items. Validity and test reliability were determined in a cohort of 91 Pompe patients (5 to 76 years of age). In addition, responsiveness of the scale to changes in clinical condition over time was examined in a subgroup of 18 patients receiving treatment and 23 untreated patients. Interrater and intrarater reliabilities were good (intraclass correlation coefficients: 0.78 to 0.98 and 0.76 to 0.98). The test correlated strongly with proximal muscle strength assessed by hand held dynamometry and manual muscle testing (rs= 0.81, rs=0.89), and showed significant differences between patient groups with different disease severities. A clinical-empirical exploration to assess responsiveness showed promising results, albeit it should be repeated in a larger group of patients. In conclusion, the Quick Motor Function Test can reliably rate clinical severity and motor function in children and adults with Pompe disease.


A new prognostic classification of rectal cancer.
Only 60% of patients having radical surgery for rectal cancer are cured of their disease. The ideal system of classification would identify just two categories--the cured and those who will die of their disease. Specimens from 379 patients who had undergone radical surgery for rectal cancer more than 20 years ago were re-examined in order to identify discrete pathological variables that independently influence long-term survival. The selected variables were given weighted scores and the score range was divided to provide four prognostic groups. The model was tested on a second data set comprising 331 patients and gave similar results. The new prognostic classification is simple to use and is superior to staging by the method of Dukes because it places twice as many patients into groups that provide a confident prediction of clinical outcome.


Improving phosphorus sustainability of sugarcane production in Brazil.
Phosphorus (P) use in global food and bioenergy production needs to become more efficient and sustainable to reduce environmental impacts and conserve a finite and critical resource (Carpenter & Bennett, Environmental Research Letters, 2011, 6, 014009; Springmann et al., Nature, 2018, 562, 519). Sugarcane is one crop with a large P footprint because production is centered on P-fixing soils with low P availability (Roy et al., Nature Plants, 2016, 2, 16043; Withers et al., Scientific Reports, 2018, 8, 2537). As global demand for processed sugar and bioethanol continues to increase, we advocate that improving P efficiency could become a key sustainability goal for the sugarcane industry. Here, we applied the 5R global P stewardship framework (Withers et al., Ambio, 2015, 44, 193) to identify more sustainable options to manage P in Brazilian sugarcane production. We show that current inputs of P fertilizer to the current crop area could be reduced by over 305 Gg, or 63%, over the next three decades by reducing unnecessary P fertilizer use, better utilization of recyclable bioresources and redesigning recommendation systems. Adoption of these 5R options would save the sugarcane industry in Brazil 528 US$ million and help safeguard global food and energy security.


Whole blood NAD and NADP concentrations are not depressed in subjects with clinical pellagra.
Population surveys for niacin deficiency are normally based on clinical signs or on biochemical measurements of urinary niacin metabolites. Status may also be determined by measurement of whole blood NAD and NADP concentrations. To compare these methods, whole blood samples and spot urine samples were collected from healthy subjects (n = 2) consuming a western diet, from patients (n = 34) diagnosed with pellagra and attending a pellagra clinic in Kuito (central Angola, where niacin deficiency is endemic), and from female community control subjects (n = 107) who had no clinical signs of pellagra. Whole blood NAD and NADP concentrations were measured by microtiter plate-based enzymatic assays and the niacin urinary metabolites 1-methyl-2-pyridone-5-carboxamide (2-PYR) and 1-methylnicotinamide (1-MN) by HPLC. In healthy volunteers, inter- and intra-day variations for NAD and NADP concentrations were much lower than for the urinary metabolites, suggesting a more stable measure of status. However, whole blood concentrations of NAD and NADP or the NAD:NADP ratio were not significantly depressed in clinical pellagra. In contrast, the concentrations of 2-PYR and 1-MN, expressed relative to either creatinine or osmolality, were lower in pellagra patients and markedly higher following treatment. The use of the combined cut-offs (2-PYR <3.0 micromol/mmol creatinine and 1-MN <1.3 micromol/mmol creatinine) gave a sensitivity of 91% and specificity of 72%. In conclusion, whole blood NAD and NADP concentrations gave an erroneously low estimate of niacin deficiency. In contrast, spot urine sample 2-PYR and 1-MN concentrations, relative to creatinine, were a sensitive and specific measure of deficiency.


Local recognition of histocompatibility differences in skin grafts.
Studies in rabbits of skin grafts tagged with tritiated thymidine indicate a greater proliferation of endothelial cells and fibroblasts at the site of an allograft than at that of an autograft as early as the first day after grafting. It appears, therefore, that allogeneic differences can be recognized and responded to locally almost at once. Labeled nuclear material is found to be transferred from the epithelial cells of skin grafts to host cells of the adjacent tissues. A mechanism therefore exists which might effect a local transfer of information on histocompatibility differences.


What should we know about dementia in the 21st century? A Delphi consensus study.
Escalating numbers of people are experiencing dementia in many countries. With increasing consumer needs, there is anticipated growth in the numbers of people providing diagnostic evaluations, treatments, and care. Ensuring a consistent and contemporary understanding of dementia across all of these groups has become a critical issue. This study aimed to reach consensus among dementia experts from English speaking countries regarding essential and contemporary knowledge about dementia. An online Delphi study was conducted to examine expert opinion concerning dementia knowledge with three rounds of data collection. A sample of dementia experts was selected by a panel of Australian experts, including a geriatrician and three professors of aged care. Purposive selection was initially undertaken with the sample expanded through snowballing. Dementia experts (N = 19) included geriatricians, psychologists, psychiatrists, neuroscientists, dementia advocates, and nurse academics from the United Kingdom, United States, and Australia. In the first round, these participants provided open-ended responses to questions determining what comprised essential knowledge about dementia. In the second round, responses were summarised into 66 discrete statements that participants rated on the basis of importance. In the third round, a rank-ordered list of the 66 statements and a group median were provided and participants rated the statements again. The degree of consensus regarding importance ratings was determined by assessing median, interquartile range, and proportion of experts scoring above predetermined thresholds. Correlation scores were calculated for each statement after the final round to identify changes in statement scores. The Delphi experts identified 36 statements about dementia that they considered essential to understanding the condition. Statements about care for a person experiencing dementia and their care giver represented the largest response category. Other statements, for which full or very high consensus was reached, related to dementia characteristics, symptoms and progression, diagnosis and assessment, and treatment and prevention. These results summarise knowledge of dementia that is considered essential across expert representatives of key stakeholder groups from three countries. This information has implications for the delivery of care to people with the condition and the development of dementia education programs.


Oligosaccharyltransferase directly binds to ribosome at a location near the translocon-binding site.
Oligosaccharyltransferase (OT) transfers high mannose-type glycans to the nascent polypeptides that are translated by the membrane-bound ribosome and translocated into the lumen of the endoplasmic reticulum through the Sec61 translocon complex. In this article, we show that purified ribosomes and OT can form a binary complex with a stoichiometry of approximately 1 to 1 in the presence of detergent. We present evidence that OT may bind to the large ribosomal subunit near the site where nascent polypeptides exit. We further show that OT and the Sec61 complex can simultaneously bind to ribosomes in vitro. Based on existing data and our findings, we propose that cotranslational translocation and N-glycosylation of nascent polypeptides are mediated by a ternary supramolecular complex consisting of OT, the Sec61 complex, and ribosomes.


Clinical practices, complications, and mortality in neurological patients with acute severe hypertension: the Studying the Treatment of Acute hyperTension registry.
To determine the demographic and clinical features, hospital complications, and predictors of 90-day mortality in neurologic patients with acute severe hypertension. Studying the Treatment of Acute hyperTension (STAT) was a multicenter (n=25) observational registry of adult critical care patients with severe hypertension treated with intravenous therapy. Emergency department or intensive care unit. A qualifying blood pressure measurement>180 mm Hg systolic or >110 mm Hg diastolic (>140/90 mm Hg for subarachnoid hemorrhage) was required for inclusion in the STAT registry. Patients with a primary neurologic admission diagnosis were included in the present analysis. All patients were treated with at least one parenteral (bolus or continuous infusion) antihypertensive agent. Of 1,566 patients included in the STAT registry, 432 (28%) had a primary neurologic diagnosis. The most common diagnoses were subarachnoid hemorrhage (38%), intracerebral hemorrhage (31%), and acute ischemic stroke (18%). The most common initial drug was labetalol (48%), followed by nicardipine (15%), hydralazine (15%), and sodium nitroprusside (13%). Mortality at 90 days was substantially higher in neurologic than in non-neurologic patients (24% vs. 6%, p<.0001). Median initial blood pressure was 183/95 mm Hg and did not differ between survivors and nonsurvivors. In a multivariable analysis, neurologic patients who died experienced lower minimal blood pressure values (median 103/45 vs. 118/55 mm Hg, p<.0001) and were less likely to experience recurrent hypertension requiring intravenous treatment (29% vs. 51%, p=.0001) than those who survived. Mortality was also associated with an increased frequency of neurologic deterioration (32% vs. 10%, p<.0001). Neurologic emergencies account for approximately 30% of hospitalized patients with severe acute hypertension, and the majority of those who die. Mortality in hypertensive neurologic patients is associated with lower minimum blood pressure values, less rebound hypertension, and a higher frequency of neurologic deterioration. Excessive blood pressure reduction may contribute to poor outcome after severe brain injury.


APOBEC3 deletion polymorphism is associated with breast cancer risk among women of European ancestry.
Copy number variations occur frequently in the genome and are a significant source of human genetic variation accounting for disease. Recently, we discovered a common deletion located in the APOBEC3A and APOBEC3B genes significantly associated with breast cancer in Chinese women. Investigating this locus in other populations would be an expedient way to evaluate the generalizability of the novel finding. We analyzed the APOBEC3 deletion in a large study of 3273 European-ancestry women (including 1671 breast cancer cases and 1602 controls) from the population-based Nashville Breast Health Study. All participants were genotyped using real-time qualitative PCR. Logistic regression was used to derive odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between the deletion polymorphism and breast cancer risk. The APOBEC3 deletion was observed in 12.4% of cases and 10.4% of controls. The deletion was significantly associated with breast cancer risk, with ORs and 95% CIs of 1.21 (1.02-1.43) associated with one-copy deletion and 2.29 (1.04-5.06) associated with two-copy deletion compared with women with no deletion (P for trend = 0.005). The positive association of the APOBEC3 deletion with breast cancer risk was similar for estrogen receptor-positive and estrogen receptor-negative breast cancer and was not modified by known breast cancer risk factors. Results from this study confirmed the association of the APOBEC3 deletion with breast cancer risk among women of European ancestry.


Function of neuromuscular synapses in the zebrafish choline-acetyltransferase mutant bajan.
We have identified a zebrafish mutant line, bajan, in which compromised motility and fatigue result from a point mutation in the gene coding choline acetyltransferase (ChAT), the enzyme responsible for acetylcholine (ACh) synthesis. Although the mutation predicts loss of ChAT function, bajan inexplicably retains low levels of neuromuscular transmission. We exploited this residual activity and determined the consequences for synaptic function. The attenuated synaptic responses were a direct consequence of a decrease in both resting mean quantal size and quantal content. To replicate behavioral fatigue in swimming, motorneurons were stimulated at high frequencies. A prominent reduction in quantal content, reflecting vesicle depletion, was coincident with a small additional reduction in quantal size. In humans, defective ChAT leads to episodic apnea, a form of congenital myasthenic syndrome characterized by use-dependent fatigue. In contrast to bajan, however, afflicted individuals exhibit a normal resting quantal size and quantal content. The fatigue in humans results from a pronounced long-lasting drop in quantal size with little or no change in quantal content. These differences have important implications for interpreting fatigue as well as on understanding the impact of ACh availability on vesicle filling and recycling.


Transmission, relatedness, and the evolution of cooperative symbionts.
Cooperative interactions between species, termed mutualisms, play a key role in shaping natural ecosystems, economically important agricultural systems, and in influencing human health. Across different mutualisms, there is significant variation in the benefit that hosts receive from their symbionts. Empirical data suggest that transmission mode can help explain this variation: vertical transmission, where symbionts infect their host's offspring, leads to symbionts that provide greater benefits to their hosts than horizontal transmission, where symbionts leave their host and infect other hosts in the population. However, two different theoretical explanations have been given for this pattern: firstly, vertical transmission aligns the fitness interests of hosts and their symbionts; secondly, vertical transmission leads to increased relatedness between symbionts sharing a host, favouring cooperation between symbionts. We used a combination of analytical models and dynamic simulations to tease these factors apart, in order to compare their separate influences and see how they interact. We found that relatedness between symbionts sharing a host, rather than transmission mode per se, was the most important factor driving symbiont cooperation. Transmission mode mattered mainly because it determined relatedness. We also found evolutionary branching throughout much of our simulation, suggesting that a combination of transmission mode and multiplicity of infections could lead to the stable coexistence of different symbiont strategies.


Social Media Based STEM Enrichment Curriculum Positively Impacts Rural Adolescent Health Measures.
Some STEM outreach programs connect students to real-world problems and challenge them to work towards solutions. Research shows one-third of children between ages 5-17 in the U.S. are overweight. Socioeconomic status, race, and parental educational attainment all influence this issue as well as living in a rural or urban area. A rural high school STEM outreach program used a social media curriculum focused on healthy lifestyles and measured impact on the health of adolescents from these backgrounds. Health screenings and college mentors were provided to 134 adolescents from 26 counties in WV. The social media intervention lasted seven months with participants using near-peer and mentor support to achieve personal health goals set at the initial health screening. The results of pre- and post-intervention health screenings were compared for any changes in health measures by student goal and participation. BMI decreased significantly in the group of participants who selected a weight loss goal, while those choosing to improve their nutrition significantly increased healthy cholesterol levels. A positive impact was seen on adolescent health outcomes through linking a high school STEM outreach program with a higher education institution to deliver STEM enrichment curriculum through social media.


Diabetes during Pregnancy in Low- and Middle-Income Countries.
Objective Our objective was to review the literature in relationship to diabetes in pregnancy in low and middle income countries. Study Design We reviewed the English language literature related to diabetes and obesity during pregnancy in low and middle income countries published over the last 20 years. Results The global prevalence of diabetes mellitus is an estimated 8% with approximately 380 million adults with this condition worldwide. Ninety percent of diabetes in adults occurs in low- and middle-income countries (LMIC). However, diabetes is highly correlated with obesity and the highest diabetes rates occur in countries with the highest obesity rates. Hyperglycemia complicates 17% of pregnancies, including women with diagnosed and undiagnosed types 1 and 2 diabetes, and gestational diabetes mellitus (GDM). In many LMIC, as pregnancy becomes more common in wealthier, older, and more obese women, pregnancies complicated by pregestational diabetes and GDM will increase. Approximately half of women with hyperglycemia in pregnancy are undiagnosed. Even with diagnosis, because of the numerous tests and criteria for abnormal glucose levels used worldwide, the prevalence of hyperglycemia in pregnancy can only be approximated. Moving forward, a single set of tests and diagnostic criteria is recommended. Although the risk factors and pregnancy outcomes for pregestational diabetes and GDM are similar in LMIC to wealthier countries, they appear to occur more commonly, and with worse outcomes because of poor access to care. In the poorest areas, inadequate antenatal and general medical care increase the difficulty in managing diabetes and its complications for women and newborns. Conclusion As obesity among women increases, diabetes in pregnancy is becoming increasingly common in LMIC. Because of lack of resources and trained personnel, and other priorities related to reducing maternal, fetal, and neonatal mortality, diagnosing and providing care to women with diabetes in pregnancy is not high on the priority lists in many LMIC.


Restricted secretion of a T-lymphocyte chemotactic cytokine by serotonin-stimulated cultured aortic endothelial cells.
The diversity of biologically active molecules produced by vascular endothelium suggests that the endothelial cell is an active participant in numerous physiological responses, including those of the immune system. In fact, the accumulation of T lymphocytes at extralymphatic inflammatory foci represents a series of interactions between lymphocytes and vascular endothelial cells. These interactions, however, may be modulated by other factors, such as vasoactive amines. In the current study, we report that serotonin-stimulated cultured bovine aortic endothelial cells (BAECs) secrete a T-lymphocyte chemotactic cytokine (endothelial cell-derived lymphocyte chemotactic activity [ED-LCA]). Supernatants from BAECs incubated with 10(-7)-10(-4) M serotonin (5-hydroxytryptamine [5-HT]) enhanced T-cell migration, which peaked at 10(-5) M 5-HT (235 +/- 18% control migration). ED-LCA was not stored in an active form in BAECs; its secretion occurred within 60 minutes of exposure to 5-HT and was blocked by two different 5-HT2 receptor antagonists. ED-LCA was not secreted after exposure of BAECs to histamine or angiotensin II, nor was it secreted by either 5-HT-stimulated bovine pulmonary arterial or human umbilical vein endothelial cells. Physicochemical characterization of ED-LCA demonstrated that it was a trypsin-sensitive protein with an apparent molecular mass of 13-15 kDa. Preparative isoelectric focusing demonstrated pIs of 6.0 and 7.5. When applied to a molecular sieve column, the chemotactic activity corresponding to these pIs eluted in the region of 13-15 kDa. Further investigation demonstrated that partially purified ED-LCA was specific for CD4+ and CD8+ T-lymphocyte subsets and did not enhance the migration of neutrophils or monocytes.(ABSTRACT TRUNCATED AT 250 WORDS)


Weighted Kolmogorov-Smirnov test: accounting for the tails.
Accurate goodness-of-fit tests for the extreme tails of empirical distributions is a very important issue, relevant in many contexts, including geophysics, insurance, and finance. We have derived exact asymptotic results for a generalization of the large-sample Kolmogorov-Smirnov test, well suited to testing these extreme tails. In passing, we have rederived and made more precise the approximate limit solutions found originally in unrelated fields, first in [L. Turban, J. Phys. A 25, 127 (1992)] and later in [P. L. Krapivsky and S. Redner, Am. J. Phys. 64, 546 (1996)].


Advancing understanding of executive function impairments and psychopathology: bridging the gap between clinical and cognitive approaches.
Executive function (EF) is essential for successfully navigating nearly all of our daily activities. Of critical importance for clinical psychological science, EF impairments are associated with most forms of psychopathology. However, despite the proliferation of research on EF in clinical populations, with notable exceptions clinical and cognitive approaches to EF have remained largely independent, leading to failures to apply theoretical and methodological advances in one field to the other field and hindering progress. First, we review the current state of knowledge of EF impairments associated with psychopathology and limitations to the previous research in light of recent advances in understanding and measuring EF. Next, we offer concrete suggestions for improving EF assessment. Last, we suggest future directions, including integrating modern models of EF with state of the art, hierarchical models of dimensional psychopathology as well as translational implications of EF-informed research on clinical science.


Dimensions of service quality in healthcare: a systematic review of literature.
Various dimensions of healthcare service quality were used and discussed in literature across the globe. This study presents an updated meaningful review of the extensive research that has been conducted on measuring dimensions of healthcare service quality. Systematic review method in current study is based on PRISMA guidelines. We searched for literature using databases such as Google, Google Scholar, PubMed and Social Science, Citation Index. In this study, we screened 1921 identified papers using search terms/phrases. Snowball strategies were adopted to extract published articles from January 1997 till December 2016. Two-hundred and fourteen papers were identified as relevant for data extraction; completed by two researchers, double checked by the other two to develop agreement in discrepancies. In total, 74 studies fulfilled our pre-defined inclusion and exclusion criteria for data analysis. Service quality is mainly measured as technical and functional, incorporating many sub-dimensions. We synthesized the information about dimensions of healthcare service quality with reference to developed and developing countries. 'Tangibility' is found to be the most common contributing factor whereas 'SERVQUAL' as the most commonly used model to measure healthcare service quality. There are core dimensions of healthcare service quality that are commonly found in all models used in current reviewed studies. We found a little difference in these core dimensions while focusing dimensions in both developed and developing countries, as mostly SERVQUAL is being used as the basic model to either generate a new one or to add further contextual dimensions. The current study ranked the contributing factors based on their frequency in literature. Based on these priorities, if factors are addressed irrespective of any context, may lead to contribute to improve healthcare quality and may provide an important information for evidence-informed decision-making.


Tissue segmentation of head and neck CT images for treatment planning: a multiatlas approach combined with intensity modeling.
Hyperthermia treatment of head and neck tumors requires accurate treatment planning, based on 3D patient models that are derived from segmented 3D images. These segmentations are currently obtained by manual outlining of the relevant tissue regions, which is a tedious and time-consuming procedure (≈ 8 h) limiting the clinical applicability of hyperthermia treatment. In this context, the authors present and evaluate an automatic segmentation algorithm for CT images of the head and neck. The proposed method combines anatomical information, based on atlas registration, with local intensity information in a graph cut framework. The method is evaluated with respect to ground truth manual delineation and compared with multiatlas-based segmentation on a dataset of 18 labeled CT images using the Dice similarity coefficient (DSC), the mean surface distance (MSD), and the Hausdorff surface distance (HSD) as evaluation measures. On a subset of 13 labeled images, the influence of different labelers on the method's accuracy is quantified and compared with the interobserver variability. For the DSC, the proposed method performs significantly better for the segmentation of all the tissues, except brain stem and spinal cord. The MSD shows a significant improvement for optical nerve, eye vitreous humor, lens, and thyroid. For the HSD, the proposed method performs significantly better for eye vitreous humor and brainstem. The proposed method has a significantly better score for DSC, MSD, and HSD than the multiatlas-based method for the eye vitreous humor. For the majority of the tissues (8/11) the segmentation accuracy of the proposed method is approaching the interobserver agreement. The authors' method showed better robustness to variations in atlas labeling compared with multiatlas segmentation. Moreover, the method improved the segmentation reproducibility compared with human observer's segmentations. In conclusion, the proposed framework provides in an accurate automatic segmentation of head and neck tissues in CT images for the generation of 3D patient models, which improves reproducibility, and substantially reduces labor involved in therapy planning.


Interaction of antibody with Forssman antigen in guinea pigs. A mechanism of adaptation to antibody- and complement-mediated injury.
Forssman antigen is a glycosphingolipid with antigenic specificity determined by extra-membrane haptenic sugars similar to blood group antigens and antigens that are the main barrier to xenogeneic organ transplantation. Herein, we describe the localization of Forssman antigen in guinea pig lungs and kidneys and the consequences of its interaction with antibodies in vitro and in vivo (Forssman reaction). Exposure of cultured guinea pig aortic endothelial cells to Forssman antibodies induced rapid redistribution of antigen-antibody complexes at the cell surface, followed by shedding that occurred by blebbing of plasma membrane as vesicles or fragments, and was associated with disappearance of antigen from the cell surface (antigenic modulation). Guinea pigs surviving frequent intravenous infections of increasing amounts of antibodies, for a total of 20 to 40 lethal doses, developed a partial or complete adaptation to generalized Forssman reaction, and adaptation was associated with partial or complete modulation of Forssman antigen at the surface of the pulmonary and, in minor degree, renal endothelial and epithelial cells. These findings support the hypothesis that modulation of endothelial carbohydrate antigens contributes to adaptation of highly vascularized organs exposed to tolerable levels of allo- or xenoantibodies.


The Influence of Intrinsic Framework Flexibility on Adsorption in Nanoporous Materials.
For applications of metal-organic frameworks (MOFs) such as gas storage and separation, flexibility is often seen as a parameter that can tune material performance. In this work we aim to determine the optimal flexibility for the shape selective separation of similarly sized molecules (e.g., Xe/Kr mixtures). To obtain systematic insight into how the flexibility impacts this type of separation, we develop a simple analytical model that predicts a material's Henry regime adsorption and selectivity as a function of flexibility. We elucidate the complex dependence of selectivity on a framework's intrinsic flexibility whereby performance is either improved or reduced with increasing flexibility, depending on the material's pore size characteristics. However, the selectivity of a material with the pore size and chemistry that already maximizes selectivity in the rigid approximation is continuously diminished with increasing flexibility, demonstrating that the globally optimal separation exists within an entirely rigid pore. Molecular simulations show that our simple model predicts performance trends that are observed when screening the adsorption behavior of flexible MOFs. These flexible simulations provide better agreement with experimental adsorption data in a high-performance material that is not captured when modeling this framework as rigid, an approximation typically made in high-throughput screening studies. We conclude that, for shape selective adsorption applications, the globally optimal material will have the optimal pore size/chemistry and minimal intrinsic flexibility even though other nonoptimal materials' selectivity can actually be improved by flexibility. Equally important, we find that flexible simulations can be critical for correctly modeling adsorption in these types of systems.


Some observations on the toxicosis of isometamidium chloride (samorin) in camels.
Healthy camels were experimentally infected with Trypanosoma evansi and then treated with isometamidium chloride (samorin) at single intravenous doses of 0.5 or 1.0 mg/kg. Five to 10 min after the drug administration, the camels at both dosages showed lacrimation, salivation, trembling, restlessness, frequent urination and defecation, followed by diarrhea. Moreover, the camels at the higher dose showed an unsteady gait for about an hour with hindleg weakness and walking backward. The animals fell to the ground, laid on their sides, and bent their necks into an "S" shaped curve. Three hours after the drug administration all the animals stood up and remained quiet. The treatment increased the concentration of plasma ammonia and total protein. No significant change was found in the plasma bilirubin concentration. Two hours after treatment, the activity of plasma cholinesterase was significantly reduced. The enzyme activity recovered 24 h after drug administration, but was still significantly below the control value. The treatment did not produce statistically significant changes in the hemogram of the infected camels. The results suggest that the drug should not be used clinically against T evansi infection due to its low margin of safety. If the drug is to be used at all in camels, pretreatment with an anticholinergic agent might be considered.


Effect of Platelet-rich Fibrin and Free Gingival Graft in the Treatment of Soft Tissue Defect preceding Implant Placement.
Free gingival graft is a procedure that is used to increase keratinized tissue around teeth and edentulous sites for future dental implants. Keratinized tissue is critical for maintainability of surgical site and flap management. Platelet-rich fibrin consists of bioactive and biological components, mainly composed of growth factors. Growth factors attract stem cells to the site of release and stimulate cell proliferation. Moreover, growth factors promote angiogenesis, which accelerates wound healing. Site preparation is critical in implant dentistry, including soft tissue and hard tissue augmentation. To improve free gingival graft (FGG) healing by using platelet-rich fibrin (PRF) at the soft tissue defect area of extracted upper right first molar in order to restore keratinized tissue and prepare the site for bone grafting followed by dental implant placement. A healthy female patient, 59 years old, presented to the dental clinic at the University at Buffalo, School of Dental Medicine, seeking dental implants to restore missing teeth. The patient had an extraction for upper right first molar 4 months ago. The surgical extraction left severe soft and hard tissue defects at the site. Free gingival graft was placed at the site to increase keratinized tissue band followed by PRF to improve healing. Cyanoacrylate adhesive was used to stabilize PRF Two months later, a full-thickness flap was reflected, and tenting screws placed with bone grafting at the site. Titanium-reenforced membrane was placed over the bone graft. Three months later, tenting screws were removed and two dental implants were placed at the site. The use of PRF accelerates the healing of FGG. More tissue handling could be achieved by increasing the kera-tinized tissue during surgical procedures. The combination of PRF and FGG could help in the healing process during soft tissue procedures.


Determinants of Intimate Partner Violence Among HIV-Positive and HIV-Negative Women in India.
To reduce the many adverse health outcomes associated with intimate partner violence (IPV), high-risk groups need to be specifically targeted in the fight against domestic violence in India. This study aims to examine the prevalence and correlates of IPV in HIV-positive and HIV-negative women from India. A convenience sample of HIV-positive and HIV-negative women responded to questionnaires to assess their experience and perception of violence. Multivariate logistic regression analysis was used to model the association between IPV and age, education, employment status, contraception use, age at first marriage, and HIV status. Although adjusting for age, education, employment status, contraception use, age at first marriage, and HIV status, women who are employed were 3.5 times more likely to suffer IPV (confidence interval [CI] = [1.5, 8.5]), women aged 18 or above at first marriage are 0.3 times less likely to face IPV (CI = [0.1, 0.6]), and women who use contraception are 7 times more likely to suffer IPV (CI = [1.4, 30.2]). Also, HIV-positive women are 3 times more likely to face sexual violence compared with HIV-negative women (CI = [1.1, 7.6]).


The perception of roll tilt in pilots during a simulated coordinated turn in a gondola centrifuge.
It has previously been reported that nonpilots underestimate the roll tilt angle after acceleration in a gondola centrifuge. The aim of the present work was to elucidate the significance of flight experience for roll tilt perception based on vestibular information. The subjective visual horizontal (SVH) was measured by means of an adjustable luminous line in darkness. Eight nonpilots (N), nine fighter pilots (F), and eight helicopter pilots (H) underwent two centrifuge runs (2 G, 5 min) heading forward and backward, respectively. The roll position of the gondola (60 degrees at 2 G) was controlled so that the subject was always upright with respect to the gravitoinertial force. Upon acceleration of the centrifuge there was a tilt of the SVH in a direction compensatory to the inclination of the gondola. This tilt was larger in the forward position [N: 17.2 +/- 6.4 degrees, F: 31.2 +/- 16.4 degrees, H: 33.6 +/- 18.2 degrees (means +/- SD)] than in the backward position (N: -5.0 +/- 6.8 degrees, F: -12.2 +/- 17.4 degrees, H: -10.4 +/- 15.4 degrees). In N the tilt declined with time, approaching zero by the end of the 2-G plateau. In the pilots it was significantly larger and did not decline. Flight experience results in an increased ability to perceive the roll tilt during movement along a curved path. That this can be revealed in a centrifuge might suggest that acceleration of the centrifuge constitutes a movement pattern which is similar, from a vestibular point of view, to that of an airplane entering a coordinated turn.


Gynaecological management of women with inherited bleeding disorders. A UK Haemophilia Centres Doctors' Organisation Guideline.
Women with inherited bleeding disorders (IBDs) may present to healthcare professionals in a variety of ways and commonly will be encountered by either haematology or gynaecology services. Heavy menstrual bleeding is very often the first manifestation of an IBD. There is a wide variation in severity of bleeding for women with IBD and diagnosis and subsequent management of their condition requires multidisciplinary specialised care which is tailored to the individual and includes excellent cross-specialty communication between gynaecology and haematology teams. This guideline is intended for both haematologists and gynaecologists who are involved in the diagnosis and management of women with bleeding disorders. It sets out recommendations about how to investigate heavy menstrual bleeding (HMB), the commonest presentation for women with IBD to hospital services, to guide physicians about how to diagnose an IBD and covers the management of women with known IBD and HMB. The second section sets out recommendations for patients known to have IBD and covers management of patients with IBD in the setting of gynaecological surgery and management for all other non-surgical gynaecological situations.


Uncovering the regional localization of inhaled salmeterol retention in the lung.
Treatment of respiratory disease with a drug delivered via inhalation is generally held as being beneficial as it provides direct access to the lung target site with a minimum systemic exposure. There is however only limited information of the regional localization of drug retention following inhalation. The aim of this study was to investigate the regional and histological localization of salmeterol retention in the lungs after inhalation and to compare it to systemic administration. Lung distribution of salmeterol delivered to rats via nebulization or intravenous (IV) injection was analyzed with high-resolution mass spectrometry imaging (MSI). Salmeterol was widely distributed in the entire section at 5 min after inhalation, by 15 min it was preferentially retained in bronchial tissue. Via a novel dual-isotope study, where salmeterol was delivered via inhalation and d3-salmeterol via IV to the same rat, could the effective gain in drug concentration associated with inhaled delivery relative to IV, expressed as a site-specific lung targeting factor, was 5-, 31-, and 45-fold for the alveolar region, bronchial sub-epithelium and epithelium, respectively. We anticipate that this MSI-based framework for quantifying regional and histological lung targeting by inhalation will accelerate discovery and development of local and more precise treatments of respiratory disease.


Simultaneous analysis of plasma and CSF by NMR and hierarchical models fusion.
Because cerebrospinal fluid (CSF) is the biofluid which interacts most closely with the central nervous system, it holds promise as a reporter of neurological disease, for example multiple sclerosis (MScl). To characterize the metabolomics profile of neuroinflammatory aspects of this disease we studied an animal model of MScl-experimental autoimmune/allergic encephalomyelitis (EAE). Because CSF also exchanges metabolites with blood via the blood-brain barrier, malfunctions occurring in the CNS may be reflected in the biochemical composition of blood plasma. The combination of blood plasma and CSF provides more complete information about the disease. Both biofluids can be studied by use of NMR spectroscopy. It is then necessary to perform combined analysis of the two different datasets. Mid-level data fusion was therefore applied to blood plasma and CSF datasets. First, relevant information was extracted from each biofluid dataset by use of linear support vector machine recursive feature elimination. The selected variables from each dataset were concatenated for joint analysis by partial least squares discriminant analysis (PLS-DA). The combined metabolomics information from plasma and CSF enables more efficient and reliable discrimination of the onset of EAE. Second, we introduced hierarchical models fusion, in which previously developed PLS-DA models are hierarchically combined. We show that this approach enables neuroinflamed rats (even on the day of onset) to be distinguished from either healthy or peripherally inflamed rats. Moreover, progression of EAE can be investigated because the model separates the onset and peak of the disease.


Magnetic resonance imaging and ultrasound for assessing parametrial infiltration in cervical cancer. A systematic review and meta-analysis.
To provide information on the current evidence regarding the diagnostic performance of ultrasound and MRI for assessing parametrial involvement in cervical cancer using the histological report as the reference standard. Meta-analysis. An extensive search of papers comparing ultrasound and MRI in assessing parametrial infiltration in cervical cancer using pathologic analysis as a reference standard was performed in Medline (Pubmed) and Web of Science from January 1990 to September 2019. Quality was assessed using the QUADAS-2 tool. Our extended search identified 205 citations but after exclusions we finally included 9 articles in the meta-analysis. The risk of bias for most studies was low for four domains were assessed in QUADAS-2. Overall, for ultrasound pooled estimated sensitivity and specificity for diagnosing parametrial infiltration was 78% (95% confidence interval [CI]:48%-93%) and 96% (95% CI=89%-99%), respectively. For MRI these figures were 68% (95% CI=54%-80%) and 91% (95% CI=84%-95%), respectively. No statistical differences were found when comparing both methods (p=0.548). Heterogeneity was low/moderate for MRI and high for ultrasound. Ultrasound and MRI have similar diagnostic performance for detecting parametrial infiltration in women with cervical cancer. This might have relevance from the clinical point of view, since ultrasound is cheaper than MRI.


First Report of the Occurrence of Tomato chlorosis virus and Tomato infectious chlorosis virus in Taiwan.
Pronounced yellowing symptoms on the lower leaves of tomato plants, similar to those caused by nitrogen deficiency, were observed in the spring of 1998 in The Asian Vegetable Research and Development Center and in farmers' fields in southern Taiwan. However, the brittleness of the discolored leaves, occasional upward leaf rolling, and abundance of whiteflies on these plants suggested the involvement of Tomato chlorosis virus (ToCV) and Tomato infectious chlorosis virus (TICV) that belong to the group of whitefly-transmitted, phloem-limited criniviruses (family Closteroviridae). Leaves of symptomatic and healthy plants were collected, and total nucleic acids were extracted from 0.2 g of leaf tissue (1). The total nucleic acids were precipitated by ethanol and dissolved in 160 μl of sterile water. Eight microliters of total nucleic acids were observed on positively charged nylon membranes (Roche Diagnostic GmbH, Roch Applied Science, Germany). Two digoxigenin-labeled riboprobes, transcribed from pTIC8-44 (complementary to the 3'-end region of TICV RNA 1) and pToC 78 (corresponding to the coat protein region of ToCV RNA 2), were used in hybridization tests to detect TICV and ToCV, respectively (2). Six of seventeen symptomatic tomato plant samples were positive with the ToCV probe, whereas none of the 13 samples reacted with the TICV probe. Similar symptoms as described above for tomato were observed on zinnia plants in the same locations. Five of eight zinnia samples gave a positive reaction with the ToCV probe. One of the ToCV positive samples also gave a positive reaction with the TICV probe. Electron microscopic examination from leaf-dip preparations of ToCV-positive leaf tissues, stained in 1% uranyl acetate, showed the presence of flexuous filamentous particles approximately 800 to 850 nm long. To our knowledge, this is the first evidence of the presence of ToCV and TICV in zinnia and ToCV in tomato in Taiwan. References: (1) A. Hadidi et al. J. Virol. Methods 30:261, 1990. (2) G. C. Wisler et al. Phytopathology 88:402, 1998.


Endovascular port-a-cath insertion in a patient with cystic fibrosis and occluded superior vena cava.
Port-a-cath insertion, for long-term intravenous antibiotic therapy, is an ideal solution for patient with cystic fibrosis. However, indwelling lines are liable to many complications including catheter thrombosis especially in patients having cystic fibrosis with hypercoagulable state. An endovascular technique for insertion of a port-a-cath in a patient having cystic fibrosis with occluded superior vena cava is reported. The technique is described in detail. In addition, a review of literature for the various methods of saving a failed central venous access in these patients was performed. The line was successfully inserted and remained patent without need of any further intervention for 20 months. In this report, several endovascular skills were used for central venous access salvage that can be used in similar situations with chronic superior vena cava occlusion, which may not be suitable for thrombolysis or stenting.


Trachoma in a rural South African community.
The prevalence of trachoma was studied in a representative sample of family units from a rural community. Evidence of current or previous infection was found in 82% of the total population, but there was a relatively low prevalence of intense upper tarsal disease. Most children acquire the disease within the first 3 yr of life, these primary infections having a tendency towards spontaneous cure without complications. The prevalence of active disease and potentially blinding sequelae is higher in elderly females than in males of the same age. Clinical and microbiological evidence suggests that trachoma is transmitted primarily within households in this community, the main source of infection appearing to be children of pre-school age. Chlamydiae were isolated from the eyes of children with intense upper tarsal disease, but not from elderly persons with similar clinical signs.


Regulation, integrase-dependent excision, and horizontal transfer of genomic islands in Legionella pneumophila.
Legionella pneumophila is a Gram-negative freshwater agent which multiplies in specialized nutrient-rich vacuoles of amoebae. When replicating in human alveolar macrophages, Legionella can cause Legionnaires' disease. Recently, we identified a new type of conjugation/type IVA secretion system (T4ASS) in L. pneumophila Corby (named trb-tra). Analogous versions of trb-tra are localized on the genomic islands Trb-1 and Trb-2. Both can exist as an episomal circular form, and Trb-1 can be transferred horizontally to other Legionella strains by conjugation. In our current work, we discovered the importance of a site-specific integrase (Int-1, lpc2818) for the excision and conjugation process of Trb-1. Furthermore, we identified the genes lvrRABC (lpc2813 to lpc2816) to be involved in the regulation of Trb-1 excision. In addition, we demonstrated for the first time that a Legionella genomic island (LGI) of L. pneumophila Corby (LpcGI-2) encodes a functional type IV secretion system. The island can be transferred horizontally by conjugation and is integrated site specifically into the genome of the transconjugants. LpcGI-2 generates three different episomal forms. The predominant episomal form, form A, is generated integrase dependently (Lpc1833) and transferred by conjugation in a pilT-dependent manner. Therefore, the genomic islands Trb-1 and LpcGI-2 should be classified as integrative and conjugative elements (ICEs). Coculture studies of L. pneumophila wild-type and mutant strains revealed that the int-1 and lvrRABC genes (located on Trb-1) as well as lpc1833 and pilT (located on LpcGI-2) do not influence the in vivo fitness of L. pneumophila in Acanthamoeba castellanii.


Religion and attitudes toward the environment: a comparison of Mormons and the general U.S. population.
Religion has been shown to influence attitudes toward an array of social issues. This manuscript focuses specifically on environmental issues, with empirical examination of the distinctiveness of contemporary Mormon environmental perspectives as contrasted with the general U.S. population. A belief in the importance of dominion over the environment is noted, by some, to be reflected in anti-environmental stance characterizing Mormon Culture Region political leaders and church members [Foltz, R. C. (2000). Mormon values and the Utah environment. Worldviews: Environment, Culture, Religion, 4, 1-19]. Yet, a set of highly regarded essays by a diverse group of Mormons, including some in church leadership positions, expresses strong personal commitments to environmental causes and point to Mormon teachings and doctrines promoting environmentalism (Williams, Smith, and Gibbs, 1998). We examine variation in environmental concern as expressed by Mormons in a local community survey undertaken in Logan, Utah, as contrasted with the nationally-representative General Social Survey (1993). We find substantial differences between Mormons and the national sample; While Mormons tended to express greater levels of environmental concern, they were less likely to have undertaken specific behaviors reflective of such concern.


Macular Atrophy in Neovascular Age-Related Macular Degeneration with Monthly versus Treat-and-Extend Ranibizumab: Findings from the TREX-AMD Trial.
To compare the enlargement rate of macular atrophy (ERMA) in eyes treated with ranibizumab monthly or using a treat-and-extend (TREX) regimen for neovascular age-related macular degeneration (AMD) or fellow control eyes, as well as analyze risk factors for macular atrophy (MA) development and progression. Eighteen-month, multicenter, randomized, controlled clinical trial. Sixty patients with treatment-naïve neovascular AMD in 1 eye randomized 1:2 to monthly or TREX ranibizumab. Patients' study and fellow eyes were followed for 18 months using spectral-domain optical coherence tomography (SD OCT) and fundus autofluorescence (FAF) imaging. The MA was quantified on FAF images using Heidelberg Region Finder software (Heidelberg Engineering, Heidelberg, Germany), with suspected areas of atrophy confirmed by SD OCT and infrared reflectance imaging. For eyes without baseline MA yet developed MA by 18 months, intervening visits were assessed to determine the first visit at which MA appeared to define progression rates. Foveal choroidal thickness (FCT), subretinal hyperreflective material (SHRM), and pigment epithelial detachment (PED), were assessed at baseline to determine whether they influenced MA progression. Mean ERMA at 18 months. Relationship between visual acuity and MA, and the baseline risk factors for ERMA were also assessed. The final analysis cohort included 88 eyes in 3 groups: monthly (n = 19), TREX (n = 30), and control fellow eyes (n = 39). Mean ERMA over 18 months was 0.39±0.67 (monthly), 1.1±1.9 (TREX), and 0.49±1 mm2 (control, P = 0.12). Mean ERMA per group among the 40.9% (n = 36) of baseline patients with MA was 0.9±1, 1.9±2.2, and 1±1.3 mm2, respectively (P = 0.31). The incidence rate of MA in the 3 groups was 40%, 0%, and 8.3%, respectively. Mann-Whitney U test revealed a statistically significant association between baseline FCT (127±46 vs. 155±55 μm, P = 0.01) and SHRM thickness (106±131 vs. 50±85 μm, P = 0.02) on MA. In eyes with no baseline MA, presence of SHRM, SHRM, and PED thickness, and presence of baseline hemorrhage were all significant predictors of new MA development (P = 0.04, 0.01, 0.04, 0.004, 0.01, respectively). Ranibizumab did not show a statistically significant influence on new MA development in eyes with neovascular AMD, whether dosed monthly or per TREX regimen. The FCT, SHRM thickness, and hemorrhage at baseline were all significant predictors of new MA.


Role of fatty acids and micronutrients in healthy ageing: a systematic review of randomised controlled trials set in the context of European dietary surveys of older adults.
Ageing is a multifaceted and inevitable process involving a decline in health and well-being that could be ameliorated by dietary modification. We review and discuss the evidence for nutritional interventions that may support healthy ageing. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used to identify randomised controlled trials investigating the role(s) of fatty acids and micronutrients in relation to markers of healthy ageing. European dietary surveys suggest that diets in elderly people are generally high in saturated fat, whereas intakes of vitamin D, magnesium, potassium, zinc and copper are below recommended levels. Thirty-four studies meeting the criteria were found, with 12 of these investigating the role of fatty acids and 22 considering intakes of micronutrients in relation to healthy ageing. Overall, these studies suggested that certain nutrients were consistent with healthy ageing; for example, omega-3 fatty acids were helpful for cognitive health, whereas combinations of calcium, vitamin D and K were linked with better bone health. Vitamin, mineral and fatty acid intakes are in need of improvement to help elderly populations achieve optimal diet quality and support healthy ageing. This could involve the judicious use of supplements alongside dietary advice. Additional research is needed to determine optimal nutrient doses, combinations and forms in relation to desired health outcomes.


Metapopulation stability in branching river networks.
Intraspecific population diversity (specifically, spatial asynchrony of population dynamics) is an essential component of metapopulation stability and persistence in nature. In 2D systems, theory predicts that metapopulation stability should increase with ecosystem size (or habitat network size): Larger ecosystems will harbor more diverse subpopulations with more stable aggregate dynamics. However, current theories developed in simplified landscapes may be inadequate to predict emergent properties of branching ecosystems, an overlooked but widespread habitat geometry. Here, we combine theory and analyses of a unique long-term dataset to show that a scale-invariant characteristic of fractal river networks, branching complexity (measured as branching probability), stabilizes watershed metapopulations. In riverine systems, each branch (i.e., tributary) exhibits distinctive ecological dynamics, and confluences serve as "merging" points of those branches. Hence, increased levels of branching complexity should confer a greater likelihood of integrating asynchronous dynamics over the landscape. We theoretically revealed that the stabilizing effect of branching complexity is a consequence of purely probabilistic processes in natural conditions, where within-branch synchrony exceeds among-branch synchrony. Contrary to current theories developed in 2D systems, metapopulation size (a variable closely related to ecosystem size) had vague effects on metapopulation stability. These theoretical predictions were supported by 18-y observations of fish populations across 31 watersheds: Our cross-watershed comparisons revealed consistent stabilizing effects of branching complexity on metapopulations of very different riverine fishes. A strong association between branching complexity and metapopulation stability is likely to be a pervasive feature of branching networks that strongly affects species persistence during rapid environmental changes.


Electroporation enhances reporter gene expression following delivery of naked plasmid DNA to the lung.
Existing methods of non-viral airway gene transfer suffer from low levels of efficiency. Electroporation has been used to enhance gene transfer in a range of tissues. Here we assess the usefulness of electroporation for enhancing gene transfer in the lungs of mice and sheep. Naked plasmid DNA (pDNA) expressing either luciferase or green fluorescent protein (GFP) was delivered to mouse lungs by instillation. Following surgical visualisation, the lungs were directly electroporated and the level and duration of luciferase activity was assessed and cell types that were positive for GFP were identified in lung cryosections. Naked pDNA was nebulised to the sheep lung and electrodes attached to the tip of a bronchoscope were used to electroporate airway segment bifurcations, Luciferase activity was assessed in electroporated and control non-electroporated regions, after 24 h. Following delivery of naked pDNA to the mouse lung, electroporation resulted in up to 400-fold higher luciferase activity than naked pDNA alone when luciferase was under the control of a cytomegalovirus (CMV) promoter. Following delivery of a plasmid containing the human polyubiquitin C (UbC) promoter, electroporation resulted in elevated luciferase activity for at least 28 days. Visualisation of GFP indicated that electroporation resulted in increased GFP detection compared with non-electroporated controls. In the sheep lung electroporation of defined sites in the airways resulted in luciferase activity 100-fold greater than naked pDNA alone. These results indicate that electroporation can be used to enhance gene transfer in the lungs of mice and sheep without compromising the duration of expression.


Evaluating the current state of the art of Huntington disease research: a scientometric analysis.
Huntington disease (HD) is an incurable neurodegenerative disorder caused by a dominant mutation on the 4th chromosome. We aim to present a scientometric analysis of the extant scientific undertakings devoted to better understanding HD. Therefore, a quantitative study was performed to examine the current state-of-the-art approaches that foster researchers' understandings of the current knowledge, research trends, and research gaps regarding this disorder. We performed literature searches of articles that were published up to September 2016 in the "ISI Web of Science™" (http://apps.webofknowledge.com/). The keyword used was "Huntington disease". Of the initial 14,036 articles that were obtained, 7732 were eligible for inclusion in the study according to their relevance. Data were classified according to language, country of publication, year, and area of concentration. The country leader regarding the number of studies published on HD is the United States, accounting for nearly 30% of all publications, followed by England and Germany, who have published 10 and 7% of all publications, respectively. Regarding the language in which the articles were written, 98% of publications were in English. The first publication to be found on HD was published in 1974. A surge of publications on HD can be seen from 1996 onward. In relation to the various knowledge areas that emerged, most publications were in the fields of neuroscience and neurology, likely because HD is a neurodegenerative disorder. Publications written in areas such as psychiatry, genetics, and molecular biology also predominated.


Relative intensity squeezing by four-wave mixing with loss: an analytic model and experimental diagnostic.
Four-wave mixing near resonance in an atomic vapor can produce relative intensity squeezed light suitable for precision measurements beyond the shot-noise limit. We develop an analytic distributed gain/loss model to describe the competition of mixing and absorption through the non-linear medium. Using a novel matrix calculus, we present closed-form expressions for the degree of relative intensity squeezing produced by this system. We use these theoretical results to analyze experimentally measured squeezing from a 85Rb vapor and demonstrate the analytic model's utility as an experimental diagnostic.