The analgesic effect of apelin-13 and its mechanism of action within the nitric oxide and serotonin pathways.

Abstract:
BACKGROUND
Apelin has various effects on a lot of systems such as central nervous system and cardiovascular system. This study investigated the possible analgesic effects of apelin-13 using the hot-plate and the tail-flick thermal analgesia tests in rats. We also evaluated the mechanism underlying the analgesic effects of apelin-13 by pretreating with Nw-nitro-L-arginine methyl ester (L-NAME) or ondansetron.

MATERIAL & METHODS
Forty male rats were used. The rats were randomly assigned to five groups according to the treatment received: Group I: Control; Group II: Morphine; Group III: Apelin-13; Group IV: Apelin-13+L-NAME; Group V: Apelin-13+Ondansetron. Acute thermal pain was modeled using the hot-plate and the tail-flick tests.

RESULTS
During the hot-plate test, i.p. Morphine and apelin-13 administered at zero- and 30 min produced significantly greater analgesic effects compared to the control. When the nitric oxide pathway was inhibited by administration of L-NAME with apelin-13, the analgesic effect continued. When apelin-13 and ondansetron were co-administered, the analgesic effect of apelin-13 disappeared at zero- and 30 min. During the tail-flick test, at 30 min, significantly higher levels of analgesia were observed in both the morphine and apelin group (which did not differ from each other) compared to the control group. L-NAME co-administered with apelin-13 did not affect the degree of analgesia, but apelin-13 co-administered with ondansetron was associated with a greater reduction in analgesia compared to the other groups.

CONCLUSION
Our results demonstrate that apelin-13 exerts an analgesic effect; co-administration of apelin-13 and ondansetron inhibits antinociception, an effect apparently mediated by five-hydroxytryptamine-three (5-HT3) receptors. Hippokratia 2015; 19 (4): 319-323.

Turtay|M G|MG|
Karabas|M|M|
Parlakpinar|H|H|
Colak|C|C|
Sagir|M|M|

analgesic
Apelin-13
nitric oxide
serotonin
rat


Autoantigen-specific immune tolerance in pathological and physiological cell death: Nanotechnology comes into view.

Abstract: Apoptotic cells are tolerogenic and can present self-antigens in the absence of inflammation, to antigen-presenting cells by the process of efferocytosis, resulting in anergy and depletion of immune effector cells. This tolerance is essential to maintain immune homeostasis and prevent systemic autoimmune diseases, such as rheumatoid arthritis and systemic lupus erythematosus. Consequently, effective efferocytosis can result in the induction of immune tolerance mediated via triggering modulatory lymphocytes and anti-inflammatory responses. Furthermore, several distinct soluble factors, receptors and pathways have been found to be involved in the efferocytosis, which are able to regulate immune tolerance by lessening antigen presentation, inhibition of T-cell proliferation and induction of regulatory T-cells. Some newly developed nanotechnology-based approaches can induce antigen-specific immunological tolerance without any systemic immunosuppression. These strategies have been explored to reverse autoimmune responses induced against various protein antigens in different diseases. In this review, we describe some nanotechnology-based approaches for the maintenance of self-tolerance using the apoptotic cell clearance process (efferocytosis) that may be able to induce immune tolerance and treat autoimmune diseases.

Tajbakhsh|Amir|A|
Farahani|Najmeh|N|
Gheibihayat|Sayed Mohammad|SM|
Mirkhabbaz|Amir Masoud|AM|
Savardashtaki|Amir|A|
Hamblin|Michael R|MR|
Mirzaei|Hamed|H|


Fertility Preservation in Female Patients with Breast Cancer - a Current Overview.

Abstract: Many premenopausal patients who develop breast cancer have not yet completed their family planning, so measures of fertility protection to preserve their fertile potential would be beneficial. Polychemotherapy causes irreversible damage to the ovarian follicles - irrespective of whether in a neoadjuvant or adjuvant setting - and this can sometimes result in permanent infertility. Depending on which cytostatic agents are used and on the age-related ovarian reserve of the woman, gonadotoxic risk must be classified as low, moderate or high. Options of fertility preservation include: a) cryopreservation of fertilised or unfertilised oocytes. After ovarian hyperstimulation, mature oocytes are retrieved by transvaginal follicle aspiration, after which they are cryopreserved, either unfertilised or on completion of IVF or ICSI treatment. During b) cryopreservation of ovarian tissue, about 50% of the ovarian cortex of one ovary is resected with the aid of a laparoscopic procedure and cryopreserved. The application of c) GnRH agonists as a medicinal therapy option is an attempt at endocrine ovarian suppression in order to protect oocytes, granulosa cells and theca cells from the cytotoxic effect of chemotherapy.

Guenther|Veronika|V|
Alkatout|Ibrahim|I|
Junkers|Wiebe|W|
Bauerschlag|Dirk|D|
Maass|Nicolai|N|
von Otte|Soeren|S|

fertility preservation
breast cancer
cryopreservation
oocytes
ovarian tissue
GnRH agonist


Role of Re species and acid cocatalyst on Ir-ReOx /SiO2 in the C-O hydrogenolysis of biomass-derived substrates.

Abstract: The catalytic performance of ReOx -modified Ir metal catalyst in the hydrogenolysis of C-O bonds is strongly dependent on the choice of solvent. The acidic property of the Re species becomes obvious in the alkane solvent, and the hydrogenolysis reaction proceeds mainly by acid-catalyzed dehydration and the subsequent metal-catalyzed hydrogenation. The acidic property of the Re species is weakened in water; however, the hydrogenolysis reaction proceeds in water via a direct mechanism involving SN 2-like attack of a hydride species at the interface between Ir and ReOx on the adsorbed Re alkoxide species. This mechanism enabled the selective dissociation of the C-O bond neighboring the CH2 OH group.

hydrogenolysis
heterogeneous catalysis
iridium
rhenium
supported catalysts


Epigenetic identification of mitogen-activated protein kinase 10 as a functional tumor suppressor and clinical significance for hepatocellular carcinoma.

Abstract:
Background
Mitogen-activated protein kinase 10 (Mapk10) is a member of the c-jun N-terminal kinases (jnk) subgroup in the MAPK superfamily, and was proposed as a tumor suppressor inactivated epigenetically. Its role in hepatocellular carcinoma (HCC) has not yet been illustrated. We aimed to investigate the expression and epigenetic regulation of mapk10 as well as its clinical significance in HCC.

Results
Mapk10 was expressed in almost all the normal tissues including liver, while we found that the protein expression of MAPK10 was significantly downregulated in clinical samples of HCC patients compared with these levels in adjacent normal tissues (29/46, P < 0.0001). Clinical significance of MAPK10 expression was then assessed in a cohort of 59 HCC cases, which indicated its negative expression was significantly correlated with advanced tumor stage (P = 0.001), more microsatellite nodules (P = 0.025), higher serum AFP (P = 0.001) and shorter overall survival time of HCC patients. Methylation was further detected in 58% of the HCC cell lines we tested and in 66% of primary HCC tissues by methylation-specific PCR (MSP), which was proved to be correlated with the silenced or downregulated expression of mapk10. To get the mechanisms more clear, the transcriptional silencing of mapk10 was reversed by pharmacological demethylation, and ectopic expression of mapk10 in silenced HCC cell lines significantly inhibited the colony formation ability, induced apoptosis, or enhanced the chemosensitivity of HCC cells to 5-fluorouracil.

Conclusion
Mapk10 appears to be a functional tumor suppressor gene frequently methylated in HCC, which could be a valuable biomarker or a new diagnosis and therapy target in a clinical setting.

Tang|Liping|L| Zhu|Shasha|S| Peng|Weiyan|W| Yin|Xuedong|X| Tan|Cui|C| Yang|Yaying|Y|

hepatocellular carcinoma
mapk10
Methylation
Tumor suppressor gene


Global Palliative Care and Cross-National Comparison: How Is Palliative Care Development Assessed?

Abstract: Indicators assessing national-level palliative care (PC) development used for cross-national comparison depict progress on this field. There is current interest on its inclusion in global monitoring frameworks.  Identify and conceptualize those most frequently used for international PC development reporting.  Systematic review.  PubMed, CINAHL, Google Scholar, and Google targeting national-level development indicators used for cross-national comparison. Additional search requesting experts' suggestions on key studies and "snow-balling" on reference section of all included studies. Identified indicators were listed and categorized in dimensions: services, use of medicines, policy, and education.  Fifty-four studies were included. Development has been evaluated using 480 different formulations of 165 indicators, 38 were highly reported. Thirty-two fell into proposed dimensions, 11 for use of medicines, 9 for policy, 7 for services, and 5 for education. Six into complementary dimensions: research, professional activity, and international cooperation. Six were the most frequently used indicators: number of PC services per population (40 reports), existence of PC national plan, strategy, or program (25), existence of palliative medicine specialization (22), availability and allocation of funds for PC (13), medical schools, including PC, in undergraduate curricula (13), and total use of opioids-morphine equivalents (11).  There is a clear pattern for national-level PC development evaluation repeatedly using a small number of indicators. Indicators addressing generalistic provision, integration into health systems, and specific fields such as pediatric lack. This study invites international discussion on a global consensus on PC-development assessment.

Arias|Natalia|N|
Garralda|Eduardo|E|
De Lima|Liliana|L|
Rhee|John Y|JY|
Centeno|Carlos|C|

D064946:Hospice and Palliative Care Nursing

global
palliative care
cross-national
comparison
development
assessment
macro indicators
national level


Oxidative stress in inflammatory cells of patient with rheumatoid arthritis: clinical efficacy of dietary antioxidants.

Abstract: Rheumatoid arthritis (RA) is an autoimmune disease responsible for significant human morbidity in modern life. However, oxidative stress is one of the key markers for determining pathophysiology of patients with RA. The interaction between cellular immune system and body's endogenous and/or exogenous antigens produce reactive oxygen species (ROS) and reactive nitrogen species (RNS) in autoimmune disease like RA. ROS and RNS include highly toxic superoxide (O2-) and peroxynitrite (ONOO-) radicals, which activate the signaling cascades of inflammatory cells to synthesize pro-inflammatory cytokines and chemokines. Previous studies reported that Th1 cytokines could promote the development of autoimmune disorders like RA, whereas the Th2 cytokines may attenuate the same diseases. An increased awareness of the relationship between food and health led to a tremendous increase of antioxidant research in the last decade. Evaluation of the efficacy of dietary antioxidants is also becoming highly acceptable in RA research. A number of dietary phytomolecules are already established as having antioxidant activity in isolated synovial cellular infiltrate or peripheral blood neutrophils and lymphocytes. This review aims to highlight the oxidative stress in inflammatory cells of patients with RA and to summarize the clinical relevance of dietary antioxidants as a first step in assessing beneficial effect, safety and dose safety ratio in patients with RA.

Oxidative stress
Inflammatory Cells
Rheumatoid arthritis
Clinical efficacy
Dietary antioxidants
Etiology


Freeze-dried eudragit-hyaluronan multicompartment liposomes to improve the intestinal bioavailability of curcumin.

Abstract: This work aimed at finding an innovative vesicle-type formulation able to improve the bioavailability of curcumin upon oral administration. To this purpose, phospholipid, Eudragit® S100 and hyaluronan sodium salt were combined to obtain eudragit-hyaluronan immobilized vesicles using an easy and environmentally-friendly method. For the first time, the two polymers were combined in a system intended for oral delivery, to enhance curcumin stability when facing the harsh environment of the gastrointestinal tract. Four different formulations were prepared, keeping constant the amount of the phospholipid and varying the eudragit-hyaluronan ratio. The freeze-drying of the samples, performed to increase their stability, led to a reduction of vesicle size and a good homogeneity of the systems, after simple rehydration with water. X-ray diffraction study demonstrated that after the freeze-drying process, curcumin remained successfully incorporated within the vesicles. All the vesicles displayed similar features: size ranging from 220 to 287nm, spherical or oval shape, multilamellar or large unilamellar morphology with a peculiar multicompartment organization involving 1-4 smaller vesicles inside. In vitro studies demonstrated the ability of the combined polymers to protect the vesicles from the harsh conditions of the gastro-intestinal tract (i.e., ionic strength and pH variation), which was confirmed in vivo by the greater deposition of curcumin in the intestinal region, as compared to the free drug in dispersion. This enhanced accumulation of curcumin provided by the eudragit-hyaluronan immobilized vesicles, together with an increase in Caco-2 cell viability exposed to hydrogen peroxide, indicated that vesicles can ensure a local protection against oxidative stress and an increase in its intestinal absorption.

Catalan-Latorre|Ana|A|
Ravaghi|Maryam|M|
Manca|Maria Letizia|ML|
Caddeo|Carla|C|
Marongiu|Francesca|F|
Ennas|Guido|G|
Escribano-Ferrer|Elvira|E|
Peris|José Esteban|JE|
Diez-Sales|Octavio|O|
Fadda|Anna Maria|AM|
Manconi|Maria|M|

Liposome
Curcumin
Polymer
Antioxidant
Intestinal biodistribution


Major correlates of mercury in small fish and common loons (Gavia immer) across four large study areas in Canada.

Abstract: We investigated mercury (Hg) concentrations in small fish (mainly yellow perch, Perca flavescens; ∼60% of fish collected) and in blood of common loons (Gavia immer) that prey upon them during the breeding season on lakes in 4 large, widely separated study areas in Canada (>13 lakes per study area; total number of lakes = 93). Although surface sediments from lakes near a base metal smelter in Flin Flon, Manitoba had the highest Hg concentrations, perch and other small fish and blood of common loon chicks sampled from these same lakes had low Hg concentrations similar to those from uncontaminated reference lakes. Multiple regression modeling with AIC analysis indicated that lake pH was by far the most important single factor influencing perch Hg concentrations in lakes across the four study areas (R(2) = 0.29). The best model was a three-variable model (pH + alkalinity + sediment Se; Wi = 0.61, R(2) = 0.85). A single-variable model (fish Hg) best explained among-lake variability in loon chick blood Hg (Wi = 0.17; R(2) = 0.53). From a toxicological risk perspective, all lakes posing a potential Hg health risk for perch and possibly other small pelagic fish species (where mean fish muscle Hg concentrations exceeded 2.4 μg/g dry wt.), and for breeding common loons (where mean fish muscle Hg concentrations exceeded 0.8 μg/g dry wt., and loon chick blood Hg exceeded 1.4 μg/g dry wt.) had pH < 6.7 and were located in eastern Canada.

Scheuhammer|A M|AM|
Lord|S I|SI|
Wayland|M|M|
Burgess|N M|NM|
Champoux|L|L|
Elliott|J E|JE|

Mercury
Fish
Common loon
Perch
Acidification
Toxicity


Acute onset of postoperative syringohydromyelia.

Abstract: Syringohydromyelia is a frequent finding in cases of tethered cord syndrome. The classical teaching is that the development and progression of a syrinx is a chronic process. We present a case report of an acute onset syringomyelia in an infant, who underwent an excision of a lumbosacral transitional lipoma and detethering of the cord. Immediately after recovery, the infant was found to have flaccid paraplegia. An emergency magnetic resonance imaging revealed a large acute onset syringomyelia for which he underwent an emergency midline myelotomy and release of fluid from the syrinx. Though the eventual recovery was good, this made us re-visit our understanding of the concept of syringohydromyelia. The case details and a plausible hypothesis for the rapid development of the syrinx are presented.

Rao|K Santosh Mohan|KS|
Balasubramaniam|Chidambaram|C|
Subramaniam|K|K|

tethered cord syndrome
Acute syringohydromyelia
postoperative complication
spinal lipoma


Aerobic endurance training improves nonalcoholic fatty liver disease (NAFLD) features via miR-33 dependent autophagy induction in high fat diet fed mice.

Abstract: Due to changes in life style, obesity and obesity related complication such as insulin resistance, type 2 diabetes and non-alcoholic fatty liver disease caused worldwide health problems. Regular exercise has been frequently prescribed to combat metabolic complication of obesity but its molecular mechanism has not been fully illustrated. We investigated molecular mechanism of lipid lowering effect of exercise training in high fat diet fed mice by focusing on miR-33 expression and autophagy pathway. 24 mice were assigned to normal chow (NC) (n=8), high-fat diet (HFD) (n=16) group and subjected to NC and HFD for 13-weeks. HFD groups were divided to sedentary (HFD n=8) or continuous endurance training (HFD+CET, n=8) subgroups. The HFD+CET mice were subjected to treadmill running for 10-weeks in 23-week HFD course. HFD increased body weight, fasting blood sugar, triglyceride, cholesterol, aspartate aminotransferase (AST), alanine aminotransferase (ALT), liver lipogenic genes expression and reduced miR-33 mRNA expression and autopahgy pathway while training program reversed them. Exogenous miR-33 mimic sequence induced autophagy and reduced lipogenesis in HepG2 cells. Autophagy induction by rapamycin reduced lipogenesis and autophagy inhibition by chloroquine, enhanced lipogenesis in HepG2 cells. These findings suggest that aerobic exercise training as a non-pharmacological therapy exerts its lipid lowering effects by miR-33 dependent autophagy induction.

Ghareghani|Parvin|P|
Shanaki|Mehrnoosh|M|
Ahmadi|Saeideh|S|
Khoshdel|Ali Reza|AR|
Rezvan|Neda|N|
Meshkani|Reza|R|
Delfan|Maryam|M|
Gorgani-Firuzjaee|Sattar|S|

D065626:Non-alcoholic Fatty Liver Disease

Autophagy
Obesity
Exercise and insulin resistance
Liver metabolism


Trusting the hand that feeds: microbes evolve to anticipate a serial transfer protocol as individuals or collectives.

Abstract:
BACKGROUND
Experimental evolution of microbes often involves a serial transfer protocol, where microbes are repeatedly diluted by transfer to a fresh medium, starting a new growth cycle. This has revealed that evolution can be remarkably reproducible, where microbes show parallel adaptations both on the level of the phenotype as well as the genotype. However, these studies also reveal a strong potential for divergent evolution, leading to diversity both between and within replicate populations. We here study how in silico evolved Virtual Microbe "wild types" (WTs) adapt to a serial transfer protocol to investigate generic evolutionary adaptations, and how these adaptations can be manifested by a variety of different mechanisms.

RESULTS
We show that all WTs evolve to anticipate the regularity of the serial transfer protocol by adopting a fine-tuned balance of growth and survival. This anticipation is done by evolving either a high yield mode, or a high growth rate mode. We find that both modes of anticipation can be achieved by individual lineages and by collectives of microbes. Moreover, these different outcomes can be achieved with or without regulation, although the individual-based anticipation without regulation is less well adapted in the high growth rate mode.

CONCLUSIONS
All our in silico WTs evolve to trust the hand that feeds by evolving to anticipate the periodicity of a serial transfer protocol, but can do so by evolving two distinct growth strategies. Furthermore, both these growth strategies can be accomplished by gene regulation, a variety of different polymorphisms, and combinations thereof. Our work reveals that, even under controlled conditions like those in the lab, it may not be possible to predict individual evolutionary trajectories, but repeated experiments may well result in only a limited number of possible outcomes.

van Dijk|Bram|B|
Meijer|Jeroen|J|
Cuypers|Thomas D|TD|
Hogeweg|Paulien|P|

Serial transfer protocol
Experimental evolution
Virtual microbes
Digital microbes
Eco-evolutionary dynamics
In silico evolution
Predicting evolution
Resource cycle


Reasons why self-referring patients attend the emergency department during daytime differ among socioeconomic groups: A survey from Flanders.

Abstract:
BACKGROUND
Numerous studies have shown that during out-of-hours vulnerable patients (regarding low-education and unemployment) are more likely to seek medical help in the emergency department (ED). However, little is known about why patients seek help in the ED during daytime hours and if these reasons differ among self-referring socioeconomic groups.

OBJECTIVES
To identify the reasons why patients opt for the ED during daytime hours when primary care services are available and identify possible social differences between socioeconomic groups.

METHODS
In 2014-2015, trained fieldworkers surveyed 723 patients visiting four EDs in Flanders using a structured interview. These quantitative data were analysed using descriptive and logistic regression analyses.

RESULTS
More than one-third of the self-referring patients reported that they attend the ED during daytime hours because they perceive their (health) problem as urgent and expect they need advanced diagnostic testing. Self-referred and low-educated patients have a 1.8 higher chance (compared to their higher-educated counterparts) of attending the ED because they expect advanced diagnostic testing. Self-referred and unemployed patients have a 3.6, 2.5 and 4.4 higher chance (compared to their employed counterparts) to opt for the ED because it is their usual source of care, family/friends refer them or they postpone care too long, respectively.

CONCLUSION
We found sociodemographic differences in motives why self-referring patients in Flanders opt for the ED during daytime hours. In general, self-referring patients attend the ED because they perceive their condition as urgent and think they may need advanced diagnostic testing.

reasons
Emergency department
socioeconomic
GP
referral


Molecular mechanisms of neurodegeneration in the entorhinal cortex that underlie its selective vulnerability during the pathogenesis of Alzheimer's disease.

Abstract: The entorhinal cortex (EC) is a vital component of the medial temporal lobe, and its contributions to cognitive processes and memory formation are supported through its extensive interconnections with the hippocampal formation. During the pathogenesis of Alzheimer's disease (AD), many of the earliest degenerative changes are seen within the EC. Neurodegeneration in the EC and hippocampus during AD has been clearly linked to impairments in memory and cognitive function, and a growing body of evidence indicates that molecular and functional neurodegeneration within the EC may play a primary role in cognitive decline in the early phases of AD. Defining the mechanisms underlying molecular neurodegeneration in the EC is crucial to determining its contributions to the pathogenesis of AD. Surprisingly few studies have focused on understanding the mechanisms of molecular neurodegeneration and selective vulnerability within the EC. However, there have been advancements indicating that early dysregulation of cellular and molecular signaling pathways in the EC involve neurodegenerative cascades including oxidative stress, neuroinflammation, glia activation, stress kinases activation, and neuronal loss. Dysfunction within the EC can impact the function of the hippocampus, which relies on entorhinal inputs, and further degeneration within the hippocampus can compound this effect, leading to severe cognitive disruption. This review assesses the molecular and cellular mechanisms underlying early degeneration in the EC during AD. These mechanisms may underlie the selective vulnerability of neuronal subpopulations in this brain region to the disease development and contribute both directly and indirectly to cognitive loss.This paper has an associated Future Leader to Watch interview with the first author of the article.

Entorhinal cortex
Alzheimer's disease
Oxidative stress
Glia activation
Amyloid beta protein
Apoptosis
Excitotoxicity
Inflammation
Tau


Is Alzheimer disease a failure of mobilizing immune defense? Lessons from cognitively fit oldest-old.

Abstract: Multifaceted evidence supports the hypothesis that inflammatory-immune mechanisms contribute to Alzheimer disease (AD) neuropathology and genetic association of several immune specific genes (TREM2, CR1, and CD33) suggests that maladaptive immune responses may be pivotal drivers of AD pathogenesis. We reviewed microglia-related data from postmortem AD studies and examined supporting evidence from AD animal models to answer the following questions: i) What is the temporal sequence of immune activation in AD progression and what is its impact on cognition? ii) Are there discordant, "primed", microglia responses in AD vs successful cognitive aging? iii) Does central nervous system (CNS) repair in aging depend on recruitment of the elements of cellular adaptive immune response such as effector T cells, and can the recruitment of systemic immune cells ameliorate AD neuropathology? iv) How effective are the immune-system-based therapeutic approaches currently employed for the treatment of AD?

Alzheimer disease
oldest-old
immune response
microglia
T cell
gene expression
inflammation
macrophage


Tissue clearing and 3D imaging in developmental biology.

Abstract: Tissue clearing increases the transparency of late developmental stages and enables deep imaging in fixed organisms. Successful implementation of these methodologies requires a good grasp of sample processing, imaging and the possibilities offered by image analysis. In this Primer, we highlight how tissue clearing can revolutionize the histological analysis of developmental processes and we advise on how to implement effective clearing protocols, imaging strategies and analysis methods for developmental biology.

Tissue clearing
3D imaging
Light-sheet microscopy


Association of lactation with maternal risk of type 2 diabetes: A systematic review and meta-analysis of observational studies.

Abstract:
AIM
To investigate the association between lactation and maternal risk of type 2 diabetes, including a potential graded association according to lactation duration.

METHODS
A systematic review and meta-analysis of observational studies that investigated the reported association between lactation (irrespective of duration, intensity or mode) and maternal risk of type 2 diabetes was conducted.

RESULTS
A total of 22 studies (17 cohort studies and five cross-sectional studies) were included in this systematic review, and 16 contributed to the meta-analysis. Studies that investigated the association of lactation with risk of type 2 diabetes in the first months after birth in women with gestational diabetes reported conflicting results. Studies with a longer follow-up showed a graded protective association for lactation and the risk of type 2 diabetes, with a potentially larger risk reduction in women with gestational diabetes than in those without gestational diabetes. Overall, ever versus never lactation was associated with a 27% lower risk of type 2 diabetes (RR 0.73, 95% CI [0.65, 0.83]). Each additional month of lactation was associated with a 1% lower risk of type 2 diabetes (RR 0.99, 95% CI [0.98, 0.99]). However, the overall quality of the studies was modest.

CONCLUSIONS
Lactation is associated with a significantly reduced risk of maternal type 2 diabetes over the life course, particularly in women with gestational diabetes. The protective effect seems to increase with longer duration of lactation. Further research is warranted to understand whether this association is modified by exposure to other risk factors.

type 2 diabetes
systematic review
meta-analysis
dose response
relationship


Flexible Li[Li0.2Ni0.13Co0.13Mn0.54]O2/Carbon Nanotubes/Nanofibrillated Celluloses Composite Electrode for High-Performance Lithium-Ion Battery.

Abstract: Rapidly-growing demand for wearable and flexible devices is boosting the development of flexible lithium ion batteries (LIBs). The exploitation of flexible electrodes with high mechanical properties and superior electrochemical performances has been a key challenge for the rapid practical application of flexible LIBs. Herein, a flexible composite electrode was prepared from the mixed solutions of Li[Li0.2Ni0.13Co0.13Mn0.54]O2 (LLOs), carbon nanotubes(CNTs), and nanofibrillated celluloses (NFCs) via a vacuum filtration method. The resulting LLOs/CNTs/NFCs electrode delivered an initial discharge capacity of 253 mAh g-1 at 0.1 C in the voltage range from 2.0 to 4.6 V, and retained a reversible capacity of 178 mAh g-1 with 83% capacity retention after 100 cycles at 1 C. The LLOs/CNTs/NFCs electrode exhibited excellent flexibility along with repeated bending in the bending test. The LLOs/CNTs/NFCs electrode after bending test remained a discharge capacity of 149 mAh g-1 after 100 cycles at 1 C, and the corresponding capacity retentions was 76%. The excellent electrochemical performance and high flexibility can be ascribed to the framework formed by CNTs with high conductivity and NFCs with good mechanical properties. The results imply that the as-fabricated electrode can be a promising candidate for the flexible LIBs.

Li|Yan|Y| Zhang|Han|H| Xiao|Zhe|Z| Wang|Renheng|R|

Li[Li0.2Ni0.13Co0.13Mn0.54]O2
carbon nanotubes
nanofibrillated celluloses
lithium ion battery
flexible electrode


Clinical characteristics of disseminated cryptococcosis in previously healthy children in China.

Abstract:
BACKGROUND
Disseminated cryptococcosis is a rare and fatal disease, and limited data exist regarding it in children. This study aimed to investigate the clinical characteristics of disseminated cryptococcosis in previously healthy children in China.

METHODS
Hospitalized patients with disseminated cryptococcosis were enrolled during January 1996 to December 2015 in Beijing Children's Hospital, Capital Medical University, China. Data on clinical manifestations, laboratory tests, treatment, and prognosis were evaluated.

RESULTS
A total of 52 pediatric patients with no underlying disease were enrolled, including 38 boys and 14 girls. Only 10 cases had a history of exposure to pigeon droppings. Fever, cough, and hepatomegaly were 3 main manifestations of disseminated cryptococcosis. However, headache was more common in patients with central nervous system (CNS) invasion than in patients with non-CNS invasion (P < 0.05). Lung (96.2%, 50/52) was the most commonly invaded organ, but only 9.6% (5/52) of patients had respiratory signs. The most common findings on chest imaging were hilar or mediastinal lymphadenopathy (46.8%, 22/47), and nodules (44.7%, 21/47), including small nodules in a scattered distribution (57.1%, 12/21) or miliary distribution (42.9%, 9/25), especially localized in subpleural area. Subsequent invasion occurred in the CNS, abdomen lymph nodes, liver, spleen, peripheral lymph nodes, and skin. In all patients, 42.3% (22/52) and 51.9% (27/52) had elevated eosinophils or IgE, respectively. The positive rate of serum cryptococcal antigen was higher, especially in patients with CNS invasion (approximately 83.3%), than with other primary methods used for pathogen detection, including cerebrospinal fluid (CSF) cryptococcal antigen, cultures of blood, bone marrow, or CSF, and CSF ink staining. The overall mortality rate of pediatric patients in our study was 11.5% (6/52). Some cases had long-term sequela, including hydrocephalus, cirrhosis, or blindness.

CONCLUSIONS
Disseminated cryptococcosis can occur in previously healthy or immunocompetent children in China. Lung and CNS were most commonly invaded by this disease. Furthermore, most cases usually showed no obvious or specific symptoms or signs, and therefore pediatricians should pay more careful attention to identify this disease.

Gao|Li-Wei|LW| Jiao|An-Xia|AX| Wu|Xi-Rong|XR| Zhao|Shun-Ying|SY| Ma|Yun|Y| Liu|Gang|G| Yin|Ju|J| Xu|Bao-Ping|BP| Shen|Kun-Ling|KL|

Disseminated cryptococcosis
Healthy
Children
Immunocompetent


Association between oxytocin and receptor genetic polymorphisms and aggression in a northern Chinese Han population with alcohol dependence.

Abstract:
OBJECTIVE
Alcohol dependence (AD) is a common chronic brain disorder precipitated by complex interactions between biological, genetic, and environmental risk factors. Aggression often occurs in the context of AD. Previous studies have shown that Oxytocin (OXT) and OXT receptor (OXTR) are involved in the regulation of aggression. The present study investigated whether variations and interactions of OXT and OXTR genes were associated with AD-related aggression in a genetically homogeneous northern Chinese Han population.

METHODS
Three hundred and twenty-four male AD patients and 510 male healthy controls (HCs) were recruited. A Chinese version of the Buss-Perry Aggression Questionnaire was used as a subjective measurement of aggressive behavior. Three variations, rs2254298, rs53576, and rs6133010 were genotyped using TaqMan and ligase detection reaction for all subjects. Generalized Multifactor Dimensionality Reduction was used to detect interactions between genetic attributes and environmental attributes.

RESULTS
The frequencies of alleles and genotypes of rs6133010 were significantly different between AD patients and HCs (p<0.001). In HCs, the effect of genotype GG of rs53576 on hostility aggression was significantly stronger than that of genotype AA and AG (p=0.001 and p=0.004, respectively), and the subjects with the interaction combination of rs6133010AA×rs2254298GG×rs53576AG exhibited significant effect on physical aggression (p=0.0107).

CONCLUSION
The present study found that rs6133010 in the OXT gene is associated with AD in the northern Chinese Han population. The polymorphisms of OXT/R may play a key role in the susceptibility of AD-related aggression.

Yang|Ling|L| Wang|Fan|F| Wang|Meiling|M| Han|Mei|M| Hu|Lufeng|L| Zheng|Minghua|M| Ma|Ji|J| Kang|Yimin|Y| Wang|Pengxiang|P| Sun|Hongqiang|H| Zuo|Wei|W| Xie|Longteng|L| Wang|Aiju|A| Yu|Dongsheng|D| Liu|Yanlong|Y|

D020022:Genetic Predisposition to Disease

Oxytocin
Polymorphism
Aggression
Alcohol dependence
Interaction


The usage, quality and relevance of information and communications technologies in patients with chronic urticaria: A UCARE study.

Abstract:
Background
Chronic urticaria (CU) is characterized by itchy recurrent wheals, angioedema, or both for 6 weeks or longer. CU can greatly impact patients' physical and emotional quality of life. Patients with chronic conditions are increasingly seeking information from information and communications technologies (ICTs) to manage their health. The objective of this study was to assess the frequency of usage and preference of ICTs from the perspective of patients with CU.

Methods
In this cross-sectional study, 1800 patients were recruited from primary healthcare centers, university hospitals or specialized clinics that form part of the UCARE (Urticaria Centers of Reference and Excellence) network throughout 16 countries. Patients were >12 years old and had physician-diagnosed chronic spontaneous urticaria (CSU) or chronic inducible urticaria (CIndU). Patients completed a 23-item questionnaire containing questions about ICT usage, including the type, frequency, preference, and quality, answers to which were recorded in a standardized database at each center. For analysis, ICTs were categorized into 3 groups as follows: one-to-one: SMS, WhatsApp, Skype, and email; one-to-many: YouTube, web browsers, and blogs or forums; many-to-many: Instagram, Twitter, Facebook, and LinkedIn.

Results
Overall, 99.6% of CU patients had access to ICT platforms and 96.7% had internet access. Daily, 85.4% patients used one-to-one ICT platforms most often, followed by one-to-many ICTs (75.5%) and many-to-many ICTs (59.2%). The daily ICT usage was highest for web browsers (72.7%) and WhatsApp (70.0%). The general usage of ICT platforms increased in patients with higher levels of education. One-to-many was the preferred ICT category for obtaining general health information (78.3%) and for CU-related information (75.4%). A web browser (77.6%) was by far the most commonly used ICT to obtain general health information, followed by YouTube (25.8%) and Facebook (16.3%). Similarly, for CU-specific information, 3 out of 4 patients (74.6%) used a web browser, 20.9% used YouTube, and 13.6% used Facebook. One in 5 (21.6%) patients did not use any form of ICT for obtaining information on CU. The quality of the information obtained from one-to-many ICTs was rated much more often as very interesting and of good quality for general health information (53.5%) and CU-related information (51.5%) as compared to the other categories.

Conclusions
Usage of ICTs for health and CU-specific information is extremely high in all countries analyzed, with web browsers being the preferred ICT platform.

Maurer|Marcus|M|
Weller|Karsten|K|
Magerl|Markus|M|
Maurer|Rasmus Robin|RR|
Vanegas|Emanuel|E|
Felix|Miguel|M|
Cherrez|Annia|A|
Mata|Valeria L|VL|
Kasperska-Zajac|Alicja|A|
Sikora|Agnieszka|A|
Fomina|Daria|D|
Kovalkova|Elena|E|
Godse|Kiran|K|
Rao|Nimmagadda Dheeraj|ND|
Khoshkhui|Maryam|M|
Rastgoo|Sahar|S|
Criado|Roberta Fachini Jardim|RFJ|
Abuzakouk|Mohamed|M|
Grandon|Deepa|D|
van Doorn|Martijn|M|
Valle|Solange Olliveira Rodrigues|SOR|
de Souza Lima|Eduardo Magalhães|EM|
Thomsen|Simon Francis|SF|
Ramón|German D|GD|
Matos Benavides|Edgar E|EE|
Bauer|Andrea|A|
Giménez-Arnau|Ana Maria|AM|
Kocatürk|Emek|E|
Guillet|Carole|C|
Ignacio Larco|Jose|J|
Zhao|Zuo-Tao|ZT|
Makris|Michael|M|
Ritchie|Carla|C|
Xepapadaki|Paraskevi|P|
Ensina|Luis Felipe|LF|
Cherrez|Sofia|S|
Cherrez-Ojeda|Ivan|I|

Information and communications technology

ICT, information and communications technologies

UCARE, Urticaria Centers of Reference and Excellence


Developing simultaneous liver-kidney transplant medical eligibility criteria while providing a safety net: A 2-year review of the OPTN's allocation policy.

Abstract: The OPTN's simultaneous liver-kidney (SLK) allocation policy, implemented August 10, 2017, established medical eligibility criteria for adult SLK candidates and created Safety Net kidney allocation priority for liver-alone recipients with new/continued renal impairment. OPTN SLK and kidney after liver (KAL) data were analyzed (registrations as of December 31, 2019, transplants pre-policy [March 20, 2015-August 9, 2017] vs. post-policy [August 10, 2017-December 31, 2019]). Ninety-four percent of SLK registrations met eligibility criteria (99% CKD: 50% dialysis, 50% eGFR). SLK transplant volume decreased from a record 740 (2017) to 676 (2018, -9%), with a subsequent increase to 728 (2019, 1.6% below 2017 volume). For KAL listings within 1 year of liver transplant, waitlist mortality rates declined post-policy versus pre-policy (27 [95% CI = 20.6-34.7] vs. 16 [11.7-20.5]) while transplant rates increased fourfold (46 [32.2-60.0] vs. 197 [171.6-224.7]). There were 234 KAL transplants post-policy (94% Safety Net priority eligible), and no significant difference in 1-year patient/graft survival vs. kidney-alone (patient: 95.9% KAL, 97.0% kidney-alone [p = .39]; graft: 94.2% KAL, 94.6% kidney-alone [p = .81]). From pre- to post-policy, the proportion of all deceased donor kidney and liver transplants that were SLK decreased (kidney: 5.1% to 4.3%; liver: 9.7% to 8.7%). SLK policy implementation interrupted the longstanding rise in SLK transplants, while Safety Net priority directed kidneys to liver recipients in need with thus far minimal impact to posttransplant outcomes.

Organ Procurement and Transplantation Network (OPTN)


Effects of Total Dietary Fiber on Cecal Microbial Community and Intestinal Morphology of Growing White Pekin Duck.

Abstract: The current study was to investigate the effects of total dietary fiber (TDF) on growth performance, cecal structure, cecal microbial community, and short-chain fatty acids (SCFAs) profiles in the cecum of growing White Pekin ducks. A total of 108 male Pekin ducks of 14-days-old were randomly allocated and fed diets containing 12.4, 14.7, and 16.2% TDF for 35 days. Each dietary treatment consisted of six replicates with six birds each. The results showed that 14.7 and 16.2% TDF treatments promoted growth performance relative to 12.4% TDF treatments (P < 0.05). A total of 14.7 and 16.2% TDF treatments significantly elevated villus height, the ratio of villus height to crypt depth and muscle layer thickness of cecum, and lowered crypt depth compared with 12.4% TDF treatment (P < 0.05). Simultaneously, 14.7 and 16.2% TDF treatments up-regulated Claudin-1 mRNA expression of barrier genes in the cecum compared with 12.4% TDF (P < 0.05). Butyrate-producing bacteria like Oscillopiraceae affiliating to the phyla Firmicutes were observed as a biomarker in the 16.2% TDF. Higher concentration of butyrate in the cecum was obtained in the 14.7% TDF compared with 12.4 and 16.2% TDF (P < 0.05). The concentrations of isobutyrate, valerate, and isovalerate in the cecum were significantly increased in the 16.2% TDF compared with 12.4 and 14.7% TDF (P < 0.05). Meanwhile, the abundance of genus UCG-005 and Enterococcus was positive correlations with isobutyrate and valerate (P < 0.05). However, the concentration of propionate in the cecum significantly decreased in 14.7 and 16.2% TDF treatments relative to 12.4% TDF treatments (P < 0.05). In summary, increasing TDF levels improved growth performance, cecal histomorphology, and barrier function of meat ducks and it might be mediated by the changes of microbiota communities, especially bloom of SCFAs-producing bacteria, which facilitated the interaction between intestinal mucosa and microbiota.

Hao|Yongsheng|Y| Ji|Zhanqing|Z| Shen|Zhongjian|Z| Wu|Yongbao|Y| Zhang|Bo|B| Tang|Jing|J| Hou|Shuisheng|S| Xie|Ming|M|

total dietary fiber
ducks
short-chain fatty acids
barrier function
microbiota


Dissecting pigment architecture of individual photosynthetic antenna complexes in solution.

Abstract: Oligomerization plays a critical role in shaping the light-harvesting properties of many photosynthetic pigment-protein complexes, but a detailed understanding of this process at the level of individual pigments is still lacking. To study the effects of oligomerization, we designed a single-molecule approach to probe the photophysical properties of individual pigment sites as a function of protein assembly state. Our method, based on the principles of anti-Brownian electrokinetic trapping of single fluorescent proteins, step-wise photobleaching, and multiparameter spectroscopy, allows pigment-specific spectroscopic information on single multipigment antennae to be recorded in a nonperturbative aqueous environment with unprecedented detail. We focus on the monomer-to-trimer transformation of allophycocyanin (APC), an important antenna protein in cyanobacteria. Our data reveal that the two chemically identical pigments in APC have different roles. One (α) is the functional pigment that red-shifts its spectral properties upon trimer formation, whereas the other (β) is a "protective" pigment that persistently quenches the excited state of α in the prefunctional, monomer state of the protein. These results show how subtleties in pigment organization give rise to functionally important aspects of energy transfer and photoprotection in antenna complexes. The method developed here should find immediate application in understanding the emergent properties of other natural and artificial light-harvesting systems.

allophycocyanin
ABEL trap
photosynthetic protein
single-molecule spectroscopy


Structural and Functional Analysis of Disease-Linked p97 ATPase Mutant Complexes.

Abstract: IBMPFD/ALS is a genetic disorder caused by a single amino acid mutation on the p97 ATPase, promoting ATPase activity and cofactor dysregulation. The disease mechanism underlying p97 ATPase malfunction remains unclear. To understand how the mutation alters the ATPase regulation, we assembled a full-length p97R155H with its p47 cofactor and first visualized their structures using single-particle cryo-EM. More than one-third of the population was the dodecameric form. Nucleotide presence dissociates the dodecamer into two hexamers for its highly elevated function. The N-domains of the p97R155H mutant all show up configurations in ADP- or ATPγS-bound states. Our functional and structural analyses showed that the p47 binding is likely to impact the p97R155H ATPase activities via changing the conformations of arginine fingers. These functional and structural analyses underline the ATPase dysregulation with the miscommunication between the functional modules of the p97R155H.

D052067:Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins

p97 ATPase
IBMPFD
p47 cofactor
single-particle cryo-EM
arginine finger
p97R155H mutation


Efficient micropropagation and assessment of genetic fidelity of Boerhaavia diffusa L- High trade medicinal plant.

Abstract: Boerhaavia diffusa L is a medicinal herb with immense pharmaceutical significance. The plant is used by many herbalist, Ayurvedic and pharmaceutical industries for production biopharmaceuticals. It is among the 46 medicinal plant species in high trade sourced mainly from wastelands and generally found in temperate regions of the world. However, the commercial bulk of this plant shows genetic variations which are the main constraint to use this plant as medicinal ingredient and to obtain high value products of pharmaceutical interest from this plant. In this study, we have regenerated the plant of Boerhaavia diffusa L through nodal explants and evaluated genetic fidelity of the micropropagated plants of Boerhaavia diffusa L with the help of random amplified polymorphic DNA (RAPD) markers. The results obtained using RAPD showed monomorphic banding pattern revealing genetic stability among the mother plant and in vitro regenerated plants of Boerhaavia diffusa L.

Patil|Kapil S|KS|
Bhalsing|Sanjivani R|SR|

Genetic fidelity
Boerhaavia diffusa L
Medicinal ingredient
Regenerated
RAPD


Crystal structure and molecular dynamics of human POLDIP2, a multifaceted adaptor protein in metabolism and genome stability.

Abstract: Polymerase δ-interacting protein 2 (POLDIP2, PDIP38) is a multifaceted, "moonlighting" protein, involved in binding protein partners from many different cellular processes, including mitochondrial metabolism and DNA replication and repair. How POLDIP2 interacts with many different proteins is unknown. Towards this goal, we present the crystal structure of POLDIP2 to 2.8 Å, which exhibited a compact two-domain β-strand-rich globular structure, confirmed by circular dichroism and small angle X-ray scattering approaches. POLDIP2 comprised canonical DUF525 and YccV domains, but with a conserved domain linker packed tightly, resulting in an "extended" YccV module. A central channel was observed, which we hypothesize could influence structural changes potentially mediated by redox conditions, following observation of a modified cysteine residue in the channel. Unstructured regions were rebuilt by ab initio modelling to generate a model of full-length POLDIP2. Molecular dynamics simulations revealed a highly dynamic N-terminal region tethered to the YccV-domain by an extended linker, potentially facilitating interactions with distal binding partners. Models of POLDIP2 complexed with two of its partners, PrimPol and PCNA, indicated that dynamic flexibility of the POLDIP2 N-terminus and loop regions likely mediate protein interactions.

POLDIP2
PDIP38
PrimPol
PCNA
DNA polymerase
protein structure


Dynamic changes in sleep-related breathing abnormalities in bilateral paramedian mesencephalon and thalamus stroke: a follow-up case study.

Abstract:
BACKGROUND
Bilateral paramedian thalamic stroke is characterized by hypersomnia, vertical gaze palsy, amnestic alteration, and apathic state. Combined lesion of the paramedian thalamus and mesencephalon bilaterally is extremely rare. Little is known about the breathing disturbances of the particular region due to the lesion. The following describes the specific case of a woman, age 62, with bilateral paramedian thalamic and mesencephalic stroke. Initially, the patient's complaints exhibited altered vigilance and vertical gaze palsy. Notably, following the acute phase, fluctuating hypersomnia was detected. The MRI (brain) revealed an ischemic lesion in the medial part of the mesencephalon and paramedian thalamus, bilaterally.

AIMS
The aim of the present study is to elucidate the involvement and characteristics of sleep-related breathing abnormalities in the clinical manifestation of the combined paramedian thalamic and mesencephalic stroke.

METHODS
Polysomnographic recordings were accomplished seven times with 1-week interval between the consecutive recordings, toward investigating the early changes of sleep and sleep-related breathing abnormalities.

RESULTS
Sleep structure examination featured a decrease in N3 and REM ratio and an increase in N1 and N2 ratio with minimal improvement during the recovery period. In contrast, significant changes were found in the breathing pattern: the initial central apnea dominance was followed by obstructive apneas with a gradual decrease of the total pathological respiratory events.

CONCLUSION
In addition to the structural abnormality of the sleep regulating network, sleep-disordered breathing is another possible cause of hypersomnia in patients afflicted with the present localization of the lesion.

Faludi|Béla|B| Tóth|Márton|M| Pusch|Gabriella|G| Komoly|Sámuel|S|

D006970:Disorders of Excessive Somnolence

Mesencephalon
Stroke
Hypersomnia
Paramedian thalamus
Central apnea
Obstructive apnea


CONSERVED AND EXAPTED FUNCTIONS OF NUCLEAR RECEPTORS IN ANIMAL DEVELOPMENT.

Abstract: The nuclear receptor gene family includes 18 members that are broadly conserved among multiple disparate animal phyla, indicating that they trace their evolutionary origins to the time at which animal life arose. Typical nuclear receptors contain two major domains: a DNA-binding domain and a C-terminal domain that may bind a lipophilic hormone. Many of these nuclear receptors play varied roles in animal development, including coordination of life cycle events and cellular differentiation. The well-studied genetic model systems of Drosophila, C. elegans, and mouse permit an evaluation of the extent to which nuclear receptor function in development is conserved or exapted (repurposed) over animal evolution. While there are some specific examples of conserved functions and pathways, there are many clear examples of exaptation. Overall, the evolutionary theme of exaptation appears to be favored over strict functional conservation. Despite strong conservation of DNA-binding domain sequences and activity, the nuclear receptors prove to be highly-flexible regulators of animal development.

exaptation
development
Drosophila
C. elegans
mouse
functional conservation


Effectiveness of iguratimod as monotherapy or combined therapy in patients with rheumatoid arthritis: a systematic review and meta-analysis of RCTs.

Abstract:
BACKGROUND
This study aims to evaluate the efficacy and safety of the iguratimod (IGU) as monotherapy or combined therapy in patients with rheumatoid arthritis (RA) by using meta-analysis.

METHODS
We searched Medline, EMBASE, Cochrane library, CNKI, Wanfang medical network from initial to 30 June, 2020, for randomized clinical trials (RCTs). Two authors independently screened the studies via reading the title, abstract, and full text. The risk of bias in individual studies was assessed using the Cochrane Risk of Bias tool. STATA 12.0 was used for pooled analysis of all included studies.

RESULTS
A total of 23 RCTs were included in this analysis. Meta-analysis showed that patients in the IGU monotherapy or combined therapy group had significantly higher ACR20 (OR = 1.97, 95% CI 1.29 to 3.00, P = 0.002), lower DAS28-CRP (SMD = -3.49, 95% CI -5.40 to -1.58, P < 0.001) and DAS28-ESR (SMD = -2.61, 95% CI -3.64 to -1.57, P < 0.001), as well as shorter duration of morning stiffness (SMD = -2.06, 95% CI -2.86 to -1.25, P < 0.001) and lower HAQ score (SMD = -0.91, 95% CI -1.61 to -0.21, P = 0.011), than those received other disease-modifying antirheumatic drugs (DMARDs) monotherapy (primarily comprising methotrexate). For the safety profile, IGU monotherapy had similar risks for gastrointestinal reactions (P = 0.070), leucopenia (P = 0.309), increment in transaminase (P = 0.321), increase of ALT (P = 0.051), and liver damage (P = 0.182) to methotrexate monotherapy, and IGU combined with other DMARDs therapy did not increase the risks of these AEs (P > 0.05).

CONCLUSIONS
Our evidence suggests that IGU is effective and tolerant as monotherapy or combined therapy especially with methotrexate in patients with active RA. IGU may be regarded as a potential alternative to methotrexate, and a preferable choice when combined with other DMARDs for the treatment of RA.

Hu|Chao-Jun|CJ| Zhang|Li|L| Zhou|Shuang|S| Jiang|Nan|N| Zhao|Jiu-Liang|JL| Wang|Qian|Q| Tian|Xin-Ping|XP| Zeng|Xiao-Feng|XF|

D016032:Randomized Controlled Trials as Topic

Iguratimod
Monotherapy
Combined therapy
Rheumatoid arthritis
Meta-analysis


Correlations between serum concentration of three bone-derived factors and obesity and visceral fat accumulation in a cohort of middle aged men and women.

Abstract:
BACKGROUND
The aim of this study was to investigate the interrelationships between three bone-derived factors [serum osteocalcin (OCN), fibroblast growth factor (FGF) 23, and neutrophil gelatinase-associated lipocalin (NGAL) levels] and body fat content and distribution, in order to reveal the potential endocrine function of bone in the development of obesity.

METHODS
We recruited 1179 people (aged 59.5 ± 6.2 years) from communities in Shanghai. Serum OCN levels were determined using an electrochemiluminescence immunoassay. Serum FGF23 and NGAL levels were determined using a sandwich enzyme-linked immunosorbent assay. The abdominal fat distribution, including visceral fat area (VFA), was assessed by magnetic resonance imaging. Visceral obesity was defined as a VFA ≥ 80 cm2.

RESULTS
Serum OCN levels were inversely correlated with body fat parameters, while FGF23 and NGAL were positively correlated (P < 0.05). After adjusting for confounders, waist circumference (W) and VFA had a closer relationship with serum OCN, FGF23, and NGAL levels than body mass index (BMI) and body fat percentage (fat%, all P < 0.05). The risk of visceral obesity significantly increased with higher FGF23 and/or NGAL levels, as well as with reduced OCN levels (all P < 0.05). In addition, serum OCN, FGF23, and NGAL levels were independently associated with visceral obesity (all P < 0.01). The relationships persisted among subjects with normal glucose tolerance or subjects with hyperglycaemia (both P < 0.05).

CONCLUSIONS
Compared to the indicators of overall adiposity such as BMI or fat%, visceral adiposity indicators (W or VFA) were more closely related to serum OCN, FGF23 and NGAL levels. There was no interaction among the relationship of three bone-derived factors with visceral obesity, which revealed the independent relationship of endocrine function of skeleton with body fat.

Xu|Yiting|Y| Ma|Xiaojing|X| Pan|Xiaoping|X| He|Xingxing|X| Xiao|Yunfeng|Y| Bao|Yuqian|Y|0000-0002-4754-3470


POLE mutations improve the prognosis of endometrial cancer via regulating cellular metabolism through AMF/AMFR signal transduction.

Abstract:
BACKGROUND
The morbidity and mortality of endometrial tumors, a common type of malignant cancer in women, have increased in recent years. POLE encodes the DNA polymerase ε, which is responsible for the leading strand DNA replication. Somatic mutations of POLE have been acknowledged in numerous cancers, resulting in the accumulation of DNA errors, leading to ultra-mutated tumors. Mutations in the exonuclease domain of POLE have been reported to improve progression-free survival in endometrial cancer. However, the potential relationship and underlying mechanism between POLE mutations and the prognosis of endometrial cancer patients remains unclear.

METHODS
The whole exome sequencing data, RNA sequencing data, and clinical information were obtained from the TCGA database and employed for the analyses in this study. The detailed mutational information was analyzed using whole exome sequencing data and the mutated genes were shown with OncoPlot. The survival curves and cox proportional hazards regression analysis were used to accessed patient prognosis, the association of clinical characteristics and prognosis. Differentially expressed genes were analyzed by the edgeR R/Bioconductor package, then the GSEA Pre-ranked tool was used for Gene Set Enrichment Analysis (GSEA) to estimate the function of genes. Expression values were clustered using hierarchical clustering with Euclidean distance and ward linkage by the dendextend R package.

RESULTS
POLE mutational status was proven to be an independent prognostic factor for endometrial cancer patients. Patients with somatic POLE mutations presented a favorable prognosis. POLE mutations regulated glycolysis and cytokine secretion, affecting cell metabolism and immune response. Autocrine motility factor (AMF)/PGI and AMFR/gp78 exhibited higher expression levels in POLE mutant patients. The comprehensive high expressions of AMFR/gp78 and low expression of POLE were associated with the favorable prognosis of endometrial cancer patients.

CONCLUSIONS
This study showed the POLE mutations a vital factor in endometrial cancer patients, leading to a higher expression of AMF/PGI and AMFR/gp78. These results suggested comprehensive consideration of the POLE mutations, expression of AMF/PGI and AMFR/gp78 may provide a more feasible and effective approach for the treatment of endometrial cancer, which might improve the prognosis.

Li|Yiran|Y| Bian|Yiding|Y| Wang|Kai|K| Wan|Xiao-Ping|XP|0000-0002-4658-3876

D060285:Receptors, Autocrine Motility Factor

Prognosis
Endometrial cancer
Autocrine motility factor (AMF)
Glucose metabolism
Polymerase ɛ (POLE) mutation


Phosphorylation of the HCN channel auxiliary subunit TRIP8b is altered in an animal model of temporal lobe epilepsy and modulates channel function.

Abstract: Temporal lobe epilepsy (TLE) is a prevalent neurological disorder with many patients experiencing poor seizure control with existing anti-epileptic drugs. Thus, novel insights into the mechanisms of epileptogenesis and identification of new drug targets can be transformative. Changes in ion channel function have been shown to play a role in generating the aberrant neuronal activity observed in TLE. Previous work demonstrates that hyperpolarization-activated cyclic nucleotide-gated (HCN) channels regulate neuronal excitability and are mislocalized within CA1 pyramidal cells in a rodent model of TLE. The subcellular distribution of HCN channels is regulated by an auxiliary subunit, tetratricopeptide repeat-containing Rab8b-interacting protein (TRIP8b), and disruption of this interaction correlates with channel mislocalization. However, the molecular mechanisms responsible for HCN channel dysregulation in TLE are unclear. Here we investigated whether changes in TRIP8b phosphorylation are sufficient to alter HCN channel function. We identified a phosphorylation site at residue Ser237 of TRIP8b that enhances binding to HCN channels and influences channel gating by altering the affinity of TRIP8b for the HCN cytoplasmic domain. Using a phosphospecific antibody, we demonstrate that TRIP8b phosphorylated at Ser237 is enriched in CA1 distal dendrites and that phosphorylation is reduced in the kainic acid model of TLE. Overall, our findings indicate that the TRIP8b-HCN interaction can be modulated by changes in phosphorylation and suggest that loss of TRIP8b phosphorylation may affect HCN channel properties during epileptogenesis. These results highlight the potential of drugs targeting posttranslational modifications to restore TRIP8b phosphorylation to reduce excitability in TLE.

D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2

Ca2+/calmodulin-dependent protein kinase II (CaMKII)


Surgical treatment of lumbar disc herniation in different ages-evaluation of 11,237 patients.

Abstract:
BACKGROUND CONTEXT
Surgical treatment of lumbar disc herniation (LDH) may lead to different outcomes in young, middle-aged, and elderly patients. However, no study has, by the same data ascertainment, evaluated referral pattern, improvement, and outcome in different age strata.

PURPOSE
This study aimed to evaluate referral pattern and outcome in patients of different ages surgically treated because of LDH.

STUDY DESIGN
This is a register study of prospectively collected data.

PATIENT SAMPLE
In SweSpine, the national Swedish register for spinal surgery, we identified 11,237 patients who between 2000 and 2010 had their outcome of LDH surgery registered in pre-, per-, and 1-year postoperative evaluations.

OUTCOME MEASURES
The data collected included age, gender, smoking habits, walking distance, preoperative duration and degree of back and leg pain, consumption of analgesics, quality of life in the patient-reported outcome measure (PROM) Short-Form 36 (SF-36) and EuroQol 5 dimensions (EQ5D), disability in the Oswestry Disability Index, operated level, type of surgery, and complications.

METHODS
We compared the outcome in patients within different 10-year age strata. IBM SPSS Statistics 22 was used in the statistical calculations. No funding was obtained for this study. The authors have no conflicts of interest to declare.

RESULTS
Patients in all ages referred to surgery had inferior PROM data compared with published normative age-matched PROM data. Referral to LDH surgery demanded of each 10-year strata statistically significantly more pain, lower quality of life, and more disability (all p<.001). Surgery markedly improved quality of life and reduced disability in all age groups (all p<.001), but with statistically significantly less PROM improvement with each older 10-year strata (all p<.001). This resulted in statistically significantly inferior PROM values for pain, quality of life, and disability postoperatively for each 10-year strata (all p<.001). There were also more complications (p<.001) with each 10-year older strata.

CONCLUSIONS
In general, older patients referred to LDH surgery have statistically significantly inferior PROM scores, improve less, and reach inferior PROM scores postoperatively. The clinical relevance must however be questioned because most patients reach, independent of age group, the defined level for a successful outcome, and the patient satisfaction rate is high.

Strömqvist|Fredrik|F|
Strömqvist|Björn|B|
Jönsson|Bo|B|
Karlsson|Magnus K|MK|

D000071066:Patient Reported Outcome Measures

Lumbar disc herniation
Outcome
Gender
PROMs
Females
Males


Effect of simvastatin on kinetics of osteoprotegrin/receptor activator nuclear kappa B Ligand mRNA expression in periapical lesions.

Abstract:
AIM
To evaluate the therapeutic effect of Simvastatin on apical periodontitis in rats by assessing the osteoblast production of receptor activator of nuclear factor-Kappa B Ligand (RANKL) and Osteoprotegerin (OPG) cytokines that are essential for bone resorption.

METHODOLOGY
Twenty-five healthy 8- to 10-week-old male rats were selected. Periapical lesions were induced by exposure of pulps through the occlusal surfaces of mandibular first molars. The pulps were extirpated and canals contaminated with saliva. The teeth were filled temporarily to make animal feeding feasible. The experimental group (n = 12) was placed on 20 mg(-1)  kg(-1)  day(-1) of Simvastatin for 10 days (3 days before and 7 days after pulp exposure) and the control group (n = 12) received a placebo. After 1, 2 and 4 weeks, the animals were sacrificed and mRNA expression of OPG/RANKL was evaluated by real-time PCR. One rat was sacrificed without any interventions (negative control) to determine the baseline expression of the mediators involved. Data were analysed by one-way anova.

RESULTS
Simvastatin significantly (P < 0.05) enhanced the expression of OPG and reduced the mRNA expression of RANKL in the experimental group compared with the control group.

CONCLUSIONS
Oral administration of Simvastatin attenuated RANKL expression and accelerated OPG expression in induced rat periapical lesions.

D060888:Real-Time Polymerase Chain Reaction

Simvastatin
RANKL
Osteoprotegerin
periapical region


Patients with borderline personality disorder and bipolar disorder: a descriptive and comparative study.

Abstract:
BACKGROUND
Bipolar disorder and borderline personality disorder (BPD) are each significant public health problems. It has been frequently noted that distinguishing BPD from bipolar disorder is challenging. Consequently, reviews and commentaries have focused on differential diagnosis and identifying clinical features to distinguish the two disorders. While there is a burgeoning literature comparing patients with BPD and bipolar disorder, much less research has characterized patients with both disorders. In the current report from the Rhode Island Methods to Improve Diagnostic Assessment and Services (MIDAS) project, we compare psychiatric outpatients with both BPD and bipolar disorder to patients with BPD without bipolar disorder and patients with bipolar disorder without BPD.

METHODS
Psychiatric outpatients presenting for treatment were evaluated with semi-structured interviews. The focus of the current study is the 517 patients with both BPD and bipolar disorder (n = 59), BPD without bipolar disorder (n = 330), and bipolar disorder without BPD (n = 128).

RESULTS
Compared to patients with bipolar disorder, the patients with bipolar disorder and BPD had more comorbid disorders, psychopathology in their first-degree relatives, childhood trauma, suicidality, hospitalizations, time unemployed, and likelihood of receiving disability payments. The added presence of bipolar disorder in patients with BPD was associated with more posttraumatic stress disorder in the patients as well as their family, more bipolar disorder and substance use disorders in their relatives, more childhood trauma, unemployment, disability, suicide attempts, and hospitalizations.

CONCLUSIONS
Patients with both bipolar disorder and BPD have more severe psychosocial morbidity than patients with only one of these disorders.

Zimmerman|Mark|M|0000-0001-8284-9910 Balling|Caroline|C| Chelminski|Iwona|I| Dalrymple|Kristy|K|

borderline personality disorder
Bipolar disorder
comorbidity


Cytogenetic effect of 5-azacytidine in patients with hematological malignancies.

Abstract:
BACKGROUND
Recently, the importance of cytogenetics has grown in the diagnosis, prognosis and treatment of leukemias and myelodysplastic syndromes. 5-azacytidine is a drug that has well-known cytogenetical effects and is approved in the treatment of myelodysplastic syndromes. To date, no studies have been performed to evaluate the impact of 5-azacytidine on the chromosomes of patients with hematological neoplasias. This study aimed to investigate the effects of 5-azacytidine on chromosomes of patients with different hematological malignancies using G-band analyses to identify possible cytogenetical alterations.

METHODS
The peripheral blood of 18 patients with hematological malignancies and 18 controls was collected in heparinized tubes. 5-azacytidine was added, at a final concentration of 10-5M, to cultures 7 hours prior to harvest.

RESULTS
Uncoiled centromeric/pericentromeric heterochromatin of chromosomes-1, 9 and 16 occurred more frequently in the patients than in controls. This higher frequency of uncoiled heterochromatin was statistically significant (p-value = 0.004) for chromosome-9. Conversely, we observed that the fragile site at 19q13 was more frequent in controls (p-value = 0.0468).

CONCLUSIONS
The results of this study suggest that satellite sequences, located in the heterochromatin of chromosome-9, are hypomethylated in hematological malignancies. This hypomethylation may contribute to the disease, activating transposable elements and/or promoting genomic instability, enabling the loss of heterozygosity of important tumor suppressor genes. An investigation of the 19q13 region may help to understand whether or not the predominant occurrence of the fragile site at 19q13 in controls is due to hypermethylation of this region.

Tsuda|Jessica Romy|JR|
Segato|Rosimeire|R|
Barbosa|Waldênia|W|
Smith|Marília de Arruda Cardoso|Mde A|
Payão|Spencer Luiz Marques|SL|


Zika Virus Outbreak - Should assisted reproduction patients avoid pregnancy?

Abstract:
OBJECTIVE
To discuss the requirement from the National Health Surveillance Agency (ANVISA), for assisted reproduction treatment patients to undergo laboratory tests for ZIKV detection, and if the public health authorities and government leaders' recommendations to women simply avoid pregnancy is prudent.

METHODS
This study was performed in a university-affiliated in vitro fertilization center in Brazil. We present a critical discussion on the risk of microcephaly due to ZIKV infection and the prevalence of other harmful pathogens to vulnerable pregnant women and infants. We assessed, 954 patients undergoing intracytoplasmic sperm injection cycles (ICSI), between April and November of 2016, concerning the results of ZIKV test, according to different regions in Brazil.

RESULTS
Patients undergoing ICSI cycles were split into groups, according to their region of origin: 28 (3.0%) were from the North, 27 (2.8%) were from the Northeast, 40 (4.2%) were from the Midwest, 830 (87.2%) were from the Southeast, and 29 (3.0%) were from the South. Concerning the diagnosis, 112 samples had a positive or inconclusive result for ZIKV, by chromatography immunoassay. These samples were re-analyzed by ELISA and no result was positive. All positive results were from the Southeast region and none from the Northeast or Midwest regions, which are considered endemic regions.

CONCLUSION
ZIKV test before the onset of assisted reproduction treatments does not rule out the risk of the infection during pregnancy. In addition, although ZIKV infection risk is extremely high, the microcephaly risk due to ZIKV is not higher than the risk of miscarriage and birth defects due to other recognized pathogens.

Braga|Daniela Paes de Almeida Ferreira|DPAF|

Zika virus
pregnancy
microcephaly
miscarriage
birth defects


Evolutionary, structural and functional analysis of the caleosin/peroxygenase gene family in the Fungi.

Abstract:
BACKGROUND
Caleosin/peroxygenases, CLO/PXG, (designated PF05042 in Pfam) are a group of genes/proteins with anomalous distributions in eukaryotic taxa. We have previously characterised CLO/PXGs in the Viridiplantae. The aim of this study was to investigate the evolution and functions of the CLO/PXGs in the Fungi and other non-plant clades and to elucidate the overall origin of this gene family.

RESULTS
CLO/PXG-like genes are distributed across the full range of fungal groups from the basal clades, Cryptomycota and Microsporidia, to the largest and most complex Dikarya species. However, the genes were only present in 243 out of 844 analysed fungal genomes. CLO/PXG-like genes have been retained in many pathogenic or parasitic fungi that have undergone considerable genomic and structural simplification, indicating that they have important functions in these species. Structural and functional analyses demonstrate that CLO/PXGs are multifunctional proteins closely related to similar proteins found in all major taxa of the Chlorophyte Division of the Viridiplantae. Transcriptome and physiological data show that fungal CLO/PXG-like genes have complex patterns of developmental and tissue-specific expression and are upregulated in response to a range of biotic and abiotic stresses as well as participating in key metabolic and developmental processes such as lipid metabolism, signalling, reproduction and pathogenesis. Biochemical data also reveal that the Aspergillus flavus CLO/PXG has specific functions in sporulation and aflatoxin production as well as playing roles in lipid droplet function.

CONCLUSIONS
In contrast to plants, CLO/PXGs only occur in about 30% of sequenced fungal genomes but are present in all major taxa. Fungal CLO/PXGs have similar but not identical roles to those in plants, including stress-related oxylipin signalling, lipid metabolism, reproduction and pathogenesis. While the presence of CLO/PXG orthologs in all plant genomes sequenced to date would suggest that they have core housekeeping functions in plants, the selective loss of CLO/PXGs in many fungal genomes suggests more restricted functions in fungi as accessory genes useful in particular environments or niches. We suggest an ancient origin of CLO/PXG-like genes in the 'last eukaryotic common ancestor' (LECA) and their subsequent loss in ancestors of the Metazoa, after the latter had diverged from the ancestral fungal lineage.

Caleosin
Peroxygenase
Fungi
Viridiplantae
Evolution
Lipid droplets
Oxylipins
Stress responses


Dual Recombinase-Mediated Cassette Exchange by Tyrosine Site-Specific Recombinases.

Abstract: Recombinase-mediated cassette exchange, or RMCE, is a genome engineering tool that can be used to swap DNA fragments of interest between two DNA molecules. In a variation of RMCE, called dual RMCE, the exchange of DNA fragments is mediated by two recombinases in contrast to one recombinase in the classic RMCE reaction. Under optimal conditions, the efficiency of dual RMCE can be quite high: up to ~45% of the transfected cells depending on the recombinase pair used to mediate the replacement reaction. Here we describe protocols for preparing for, performing, and optimizing the parameters of dual RMCE.

Voziyanova|Eugenia|E|
Anderson|Rachelle P|RP|
Voziyanov|Yuri|Y|

D004254:DNA Nucleotidyltransferases
D018390:Gene Targeting
D017930:Genes, Reporter
D056426:Genetic Loci
D005822:Genetic Vectors
D049452:Green Fluorescent Proteins
D057809:HEK293 Cells
D006801:Humans
D019426:Integrases
D008164:Luminescent Proteins
D016297:Mutagenesis, Site-Directed
D011401:Promoter Regions, Genetic
D011995:Recombination, Genetic
D014162:Transfection
D014443:Tyrosine

Dual recombinase-mediated cassette exchange


A new strategy for battling bacterial resistance: Turning potent, non-selective and potentially non-resistance-inducing biocides into selective ones.

Abstract: Antibiotic alternatives are in great need for combating antibiotic resistance. Selective delivery of a potent non-selective non-resistance-inducing biocide (C17) to MRSA was achieved by encapsulating it in solid lipid nanoparticles (SLNs) conjugated with a MRSA-specific antibody (termed as "Ab"). The C17-loaded Ab-conjugated SLNs (C17-SLN-Ab) demonstrated significantly better antimicrobial activity than its antibody free counterpart (C17-loaded SLN) and C17-loaded SLN with a non-specific IgG antibody. In a new MRSA/fibroblast co-culture assay, C17-SLN-Ab showed selective toxicity toward MRSA than fibroblast cells. C17-SLN-Ab possesses double selectivity, exhibiting higher toxicity to MRSA than to Pseudomonas aeruginosa. This same strategy was used to successfully increase C17's selectivity against E. coli K12 by switching the conjugated anti-MRSA antibody to an anti-E. coli antibody, demonstrating versatility of this new strategy. This proof-of-concept research can be extended to other non-selective antimicrobials, against which bacterial resistance is unlikely to develop, to generate a new group of promising antibiotic alternatives.

Ghanbar|Sadegh|S|
Fumakia|Miral|M|
Ho|Emmanuel A|EA|
Liu|Song|S|

Biocide
Solid lipid nanoparticle
Antibody
Active targeting
Selective kill


Housing Conditions Contribute to Underweight in Children: An Example From Rural Villages in Southeast Sulawesi, Indonesia.

Abstract:
Objectives
The prevalence of underweight in children under 5 years of age is anomalously high in Konawe District, Southeast Sulawesi Province, Indonesia. This state of affairs may be related to poor housing conditions, such as limited access to clean water, the absence of a sanitary latrine, and the use of poor housing materials. Therefore, this study aimed to examine the effect of housing conditions on underweight in under-5 children in Konawe District.

Methods
This study was conducted in 2013 in 5 health centres in Konawe District, Southeast Sulawesi Province, and used a case-control study design. The study recruited 400 under-5 children, including 100 of whom were cases and 300 of whom were age-matched controls (1:3). Cases were underweight children, while the controls were children with a normal nutritional status. The independent variables were the availability and types of water and latrine facilities and housing materials (roof, wall, and floor). The statistical analysis used Cox regression.

Results
A lack of water availability (odds ratio [OR], 5.0; 95% confidence interval [CI], 2.7 to 9.5; p<0.001), a lack of latrine availability in the home (OR, 2.5; 95% CI, 1.5 to 4.0; p<0.001), and poor-quality roofing materials (OR, 1.7; 95% CI, 1.1 to 2.7; p<0.02) significantly contributed to underweight in children. In contrast, the walls and the floors did not contribute to under-5 year children being underweight (p=0.09 and p=0.71, respectively).

Conclusions
Sanitation facilities and roofing were identified as important factors to address in order to improve children's nutritional status. Children's health status was directly impacted by food intake via their nutritional status.

Underweight
Indonesia
Case-control studies
Nutritional status
Child
Living facilities


Serum C-peptide and osteocalcin levels in children with recently diagnosed diabetes.

Abstract:
Background
We explored the association of C-peptide (marker of secreted insulin), proinsulin and proinsulin ⁄C-peptide ratio (PI/C) (markers of beta-cell endoplasmic reticulum [ER] stress) with undercarboxylated (uOC) and carboxylated osteocalcin (cOC) and their ratio (uOC/cOC) in children with recently diagnosed type 1 (T1D) or type 2 diabetes (T2D), and the correlation of these variables with partial remission (PR) in children with T1D.

Methods
Demographic and clinical data of children with new-onset diabetes (n = 68; median age = 12.2 years; 33.8% non-Hispanic White, 45.6% Hispanic/Latino, 16.2% African American and 4.4% other) were collected at diagnosis and during the first (V1), second (V2) and third clinical visits at 9.0, 32.0 and 175.7 weeks, respectively. Serum proinsulin, C-peptide, uOC and cOC values were measured 7.0 weeks after diagnosis. PR was defined as insulin dose-adjusted HbA1c (IDAA1c) ≤9.

Results
In children with new-onset T1D with DKA (33.3%) or T2D (29.4%), Spearman's correlation coefficient revealed a positive association between the C-peptide levels and both uOC and uOC/cOC ratio. In T1D (n = 48), both higher serum C-peptide levels and low PI:C ratio were associated with higher BMI percentile (β = 0.02, P = .001; β = -0.01, P = .02, respectively) and older age at diagnosis (β = 0.13, P = .001; β = -0.12, P = .001, respectively). Furthermore, in children with T1D, C-peptide levels at V1 correlated with IDAA1c ≤ 9 at V1 (P = .04).

Conclusion
C-peptide levels are associated with a higher uOC and uOC/cOC ratio in paediatric diabetes. In new-onset T1D children, older age and higher BMI were associated with lower beta-cell stress and higher preserved function, which was predictive of PR on follow-up.

osteocalcin diabetes paediatrics C‐peptide


Effects of High-Temperature Storage on the Elasticity Modulus of an Epoxy Molding Compound.

Abstract: Changes in the elasticity modulus of an epoxy molding compound (EMC), an electronic packaging polymer, under high-temperature air storage conditions, are discussed in this study. The elasticity modulus of EMC had two different compositions (different filling contents) under different temperatures (175, 200, and 225 °C) and aging times (100, 500, and 1500 h), which were analyzed by using dynamic mechanic analysis technology. The results revealed that the elasticity modulus increased in the thermal aging process, with an increase in the temperature and the aging time. The increments of the glassy and rubbery states were similar. However, the growing rate was significantly different, and the growth of the rubbery state was significantly higher than that of the glassy state. The filling content influenced the degree of aging of the materials significantly. At a low filling content, long-term aging under high temperatures completely changed the material structure, and the mechanical properties of the polymer were reduced.

Li|Ruifeng|R| Yang|Daoguo|D| Zhang|Ping|P|0000-0001-8639-6605 Niu|Fanfan|F| Cai|Miao|M|0000-0001-5836-0998 Zhang|Guoqi|G|

high-temperature storage
elasticity modulus
epoxy molding compound
microelectronics reliability


Identifying risk factors for postoperative major complications in staged implant-based breast reconstruction with AlloDerm.

Abstract: Acellular dermal matrices (ADM) have reportedly been associated with postoperative complications following breast reconstruction. The purpose of this study was to identify risk factors predictive of major postoperative complications after staged implant-based breast reconstruction with ADM. A retrospective study of all patients who underwent implant-based breast reconstruction with AlloDerm between 2013 and 2017 was conducted. Demographic information, procedural data, and postoperative complications were retrieved. The main objective was to analyze patient and procedural factors associated with the occurrence of major complications, including postoperative readmission and loss of reconstruction. A total of 166 patients (288 breasts) were included. Major complications were noted in 19.9%. The overall rate of infection and mastectomy skin necrosis was 16.9% and 6.6%, respectively. Readmission occurred in 16.3% and loss of reconstruction occurred in 8.4% of patients. Risk factors for major complications included body mass index (BMI) >27.0 kg/m2 (OR 2.46; p = 0.041), higher tissue expander volume (p = 0.049), history of chemotherapy (OR 2.20; p = 0.047) and radiotherapy (OR 2.22; p = 0.040). Loss of reconstruction was associated with a BMI >27.0 kg/m2 (OR 4.00; p = 0.012), tobacco use (OR 6.64, p = 0.006), and higher tissue expander volume (p = 0.035). Similarly, readmission was associated with higher tissue expander volume (p = 0.042). In conclusion, a variety of factors were identified to be associated with major complications, including higher BMI, increased tissue expander volume, as well as history of chemotherapy and radiation. This information is valuable for pre-operative counseling and for future comparative studies between different ADM types.

Remington|Austin C|AC|
Gurtner|Geoffrey C|GC|
Wan|Derrick C|DC|
Nguyen|Dung|D|
Momeni|Arash|A|0000-0002-6452-751X

D000328:Adult
D015992:Body Mass Index
D019928:Breast Implantation
D018427:Breast Implants
D001943:Breast Neoplasms
D015331:Cohort Studies
D003094:Collagen
D005260:Female
D006801:Humans
D016462:Mammaplasty
D008875:Middle Aged
D010359:Patient Readmission
D011183:Postoperative Complications
D012189:Retrospective Studies
D015625:Tissue Expansion Devices

Breast reconstruction
Tissue
Expander
Acellular dermal matrix
Breast implant
Plastic surgery


In vitro Arthrographis kalrae biofilm formation: Scanning electron microscopy and cytotoxic analysis.

Abstract: To our knowledge, this study represents the first demonstration of Arthrographis kalrae biofilm formation in vitro by scanning electron microscopy and the distinct cytotoxic activity between planktonic and biofilm extracts on RAW 264.7 cell line. Higher activity was observed with biofilm. It could impact host immune response, that require furthers study.

Souza|Bianca Dorana de Oliveira|BDO|
Arcos|Janneth Josefina Escobar|JJE|
Nakamura|Celso Vataru|CV|
Nagashima|Luciene Airy|LA|
Sano|Ayako|A|
Ono|Mario Augusto|MA|
Itano|Eiko Nakagawa|EN|

Cytotoxicity
Fungi
Macrophage
Virulence factors


The efficacy of education programme for preventing constipation in women.

Abstract: This study was performed to evaluate the efficiency of the education programme for prevention of constipation in women. This study was performed as a pre-test-posttest design. Thirty-five women were included who have constipation problem. Data were collected by questionnaire: Constipation Severity Instrument (CSI), Constipation Visual Analogue Scale (CVAS) and Bristol Stool Chart (BSC). Eight home visits were made for each of the women and they were followed up for 3 months. Participants received an individual education programme that included advice on dietary consumption such as pulpy-fibrous nutrient consumption, fluid intake, an exercise regime and counselling about optimal position to defecate. The subscales of 'Colonic Inertia' and 'Pain', and CSI total mean scores and CVAS mean scores were decreased significantly after education programme (P < 0.05). According to the BSC, 71.5% of the women stated their stool form to be 'sausage-shaped, but lumpy' before the education programme, but after the said programme the percentage had dropped to 17.1%. Education programme given to women who had constipation were determined to have been effective in alleviating constipation. Nurses should develop appropriate and effective strategies to help women prevent constipation.


In Pursuit of Three Theories: Authoritarianism, Relative Deprivation, and Intergroup Contact.

Abstract: Throughout my career, I have pursued three theories related to intergroup prejudice--each with a different mentor. Each theory and its supporting research help us to understand prejudice and ways to ameliorate the problem. This autobiographical review article summarizes some of the advances in these three areas during the past six decades. For authoritarianism, the article advocates removing political content from its measurement, linking it with threat and dismissive-avoidant attachment, and studying how authoritarians avoid intergroup contact. Increased work on relative deprivation made possible an extensive meta-analysis that shows the theory, when appropriately measured, has far broader effects than previously thought. Increased research attention to intergroup contact similarly made possible a meta-analysis that established the pervasive effectiveness of intergroup contact to reduce prejudice under a wide range of conditions. The article closes by demonstrating how the three theories relate to each other and contribute to our understanding of prejudice and its reduction.

D001318:Authoritarianism
D006126:Group Processes
D049673:History, 20th Century
D049674:History, 21st Century
D006801:Humans
D007398:Interpersonal Relations
D011287:Prejudice
D011593:Psychology, Social
D012933:Social Identification
D012938:Social Perception

authoritarianism
relative deprivation
intergroup contact
prejudice
Autobiography
Gordon Allport
Samuel Stouffer


Pigmented Villonodular Synovitis: A Rare Case of Anterior Ankle Impingement.

Abstract:
Introduction
Anterior ankle impingement is characterized by a painful range of motion (ROM)limitation of tibiotarsal joint. More than 70% of cases are secondary to trauma or repetitive microtrauma of the anterior aspect of the ankle such as it occurs during ball kicking ("footballer's ankle") or forced plantar flexion (ballet dancers, volleyball players, and runners) in people practicing sport for many years. There are other causes of anterior ankle impingement. We report a case of villonodular synovitis that, also less common, has to be considered in diagnostic flowchart.

Case Report
In this paper, we report a rare case of pigmented villonodular synovitis (PVNS) in a 37-year-old Caucasian male soccer player, with a 4-year story of ankle swelling and ROM painful limitation.

Conclusion
PVNS, although it is an unusual cause of anterior ankle impingement, needs an early diagnosis and surgical excision to prevent extra-articular extension of the mass, cartilage damage, and soft tissue compression.

Morelli|Federico|F| Princi|Giorgio|G| Rossato|Alessio|A| Iorio|Raffaele|R| Ferretti|Andrea|A|

pigmented villonodular synovitis
Ankle
impingement


Dosimetry analysis of panoramic-imaging devices in different-sized phantoms.

Abstract: The aim of this study is to measure the radiographic dose in adult, adolescent, and child head-sized PMMA phantoms for three panoramic-imaging devices: the panoramic mode on two CBCT machines (Carestream 9300 and i-CAT NG) and the Planmeca ProMax 2D. A SEDENTEXCT dose index adult phantom and custom-built adolescent and pediatric PMMA dosimetry phantoms were used. Panoramic radiographs were performed using a Planmeca ProMax 2D and the panoramic mode on a Carestream 9300 CBCT and an i-CAT NG using the protocols used clinically. Point dose measurements were performed at the center, around the periphery and on the surface of each phantom using a thimble ionization chamber. Five repeat measurements were taken at each location. For each machine, single-factor ANOVA was conducted to determine dose differences between protocols in each phantom, as well as determine the differences in absorbed dose when the same protocol was used for different-sized phantoms. For any individual phantom, using protocols with lower kVp, mA, or acquisition times resulted in statistically significant dose savings, as expected. When the same protocol was used for different-sized phantoms, the smaller phantom had a higher radiation dose due to less attenuation of x-rays by the smaller phantom and differences in the positioning of the ion chamber relative to the focal trough. The panoramic-mode on the CBCT machines produce images suitable for clinical use with similar dose levels to the stand-alone panoramic device. Significant dose savings may result by selecting age- and size- appropriate protocols for pediatric patients, but a wider range of protocols for children and adolescents may be beneficial.

Wahid|Muizz A|MA|
Choi|Ella|E|
MacDonald|David S|DS|
Ford|Nancy L|NL|

paediatric dentistry
panoramic radiography
radiation dosimetry
radiographic phantoms
radiology


Stressors affecting nursing students in Pakistan.

Abstract:
AIM
To determine factors contributing to stress experienced by preregistration nursing students in Pakistan, using the Stressors in Nursing Students scale. The aim was to explore the psychometric properties of this instrument and to investigate the effect of a range of demographic variables on the perception of stressors in nursing students.

BACKGROUND
Nursing is a stressful profession, and nursing students may experience more stress due to competing demands and challenges of nursing education, assessment, placements and worries about employment prospects.

METHODS
In this cross-sectional survey, data from 726 nursing students from 11 schools of nursing in Karachi, Pakistan, were collected using a questionnaire. Data were analysed using descriptive as well inferential statistics. An exploratory factor analysis was also conducted.

RESULTS
There was no apparent factor structure to the Stressors in Nursing Students scale, unlike in previous studies. The total score on the Stressors in Nursing Students scale was related to gender with males scoring higher. The score generally increased over 4 years of the programme, and students in private schools of nursing scored higher than those in public schools of nursing.

CONCLUSION
Nursing students in Pakistan do not appear to differentiate between different stressors, and this may be due to cultural differences in the students and to the structure of the programme and the articulation between the academic and clinical aspects. Likewise, cultural reasons may account for differences between stress experienced by male and female students.

IMPLICATIONS FOR NURSING AND POLICY
The fact that scores on the Stressors in Nursing Students scale increased over 4 years of the programme and males scored higher than females should alert nursing schools and policymakers related to nursing education and workforce to pay attention to prevent attrition from nursing programmes.

Stressors
Nurses
Nursing Students
Stress
Psychometric


Cellular Uptake Pathways of Nanoparticles: Process of Endocytosis and Factors Affecting Their Fate.

Abstract:
BACKGROUND
Efficient and controlled internalization of NPs into the cells depends on their physicochemical properties and dynamics of the plasma membrane. NPs-cell interaction is a complex process that decides the fate of NPs internalization through different endocytosis pathways.

OBJECTIVE
The aim of this review is to highlight the physicochemical properties of synthesized nanoparticles (NPs) and their interaction with the cellular-dynamics and pathways like phagocytosis, pinocytosis, macropinocytosis, clathrin, and caveolae-mediated endocytosis and the involvement of effector proteins domain such as clathrin, AP2, caveolin, Arf6, Cdc42, dynamin and cell surface receptors during the endocytosis process of NPs.

METHOD
An electronic search was performed to explore the focused reviews and research articles on types of endocytosis and physicochemical properties of nanoparticles and their impact on cellular internalizations. The search was limited to peer-reviewed journals in the PubMed database.

RESULTS
This article discusses in detail how different types of NPs and their physicochemical properties such as size, shape, aspect ratio, surface charge, hydrophobicity, elasticity, stiffness, corona formation, surface functionalization changes the pattern of endocytosis in the presence of different pharmacological blockers. Some external forces like a magnetic field, electric field, and ultrasound exploit the cell membrane dynamics to permeabilize them for efficient internalization with respect to fundamental principles of membrane bending and pore formation.

CONCLUSION
This review will be useful to attract and guide the audience to understand the endocytosis mechanism and their pattern with respect to physicochemical properties of NPs to improve their efficacy and targeting to achieve the impactful outcome in drug-delivery and theranostics applications.

Varma|Sameer|S|
Dey|Smita|S|
S P|Dhanabal|D|

Internalization
phagocytosis
macropinocytosis
clathrin
functionalization
magnetic field
ultrasound
caveolae
permeation


Frequent IDH2 R172 mutations in undifferentiated and poorly-differentiated sinonasal carcinomas.

Abstract: Sinonasal undifferentiated carcinoma (SNUC) is a high-grade malignancy with limited treatment options and poor outcome. A morphological spectrum of 47 sinonasal tumours including 17 (36.2%) SNUCs was analysed at genomic level. Thirty carcinomas (cohort 1) were subjected to a hybridization exon-capture next-generation sequencing assay (MSK-IMPACTTM ) to interrogate somatic variants in 279 or 410 cancer-related genes. Seventeen sinonasal tumours (cohort 2) were examined only for the presence of IDH1/2 exon 4 mutations by Sanger sequencing. IDH2 R172 single nucleotide variants were overall detected in 14 (82.4%) SNUCs, in two (20%) poorly-differentiated carcinomas with glandular/acinar differentiation, and in one of two high-grade neuroendocrine carcinomas, large cell type (HGNECs). No IDH2 mutation was detected in any of five olfactory neuroblastomas or in any of five SMARCB1-deficient carcinomas. Among 12 IDH2-mutated cases in cohort 1, five (41.7%) harboured co-existing TP53 mutations, four (33.3%) CDKN2A/2B loss-of-function alterations, four (33.3%) MYC amplification, and three (25%) had concurrent SETD2 mutations. AKT1 E17K and KIT D816V hotspot variants were each detected in one IDH2-mutated SNUC. The vast majority of SNUCs and variable proportions of other poorly-differentiated sinonasal carcinomas may be amenable to IDH2-targeted therapy. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Dogan|Snjezana|S|0000-0002-4905-8946
Chute|Deborah J|DJ|
Xu|Bin|B|
Ptashkin|Ryan N|RN|
Chandramohan|Raghu|R|
Casanova-Murphy|Jacklyn|J|
Nafa|Khedoudja|K|
Bishop|Justin A|JA|
Chiosea|Simion I|SI|
Stelow|Edward B|EB|
Ganly|Ian|I|
Pfister|David G|DG|
Katabi|Nora|N|
Ghossein|Ronald A|RA|
Berger|Michael F|MF|

IDH2 R172
sinonasal undifferentiated carcinoma
SNUC


Efficacy of krypton laser photodynamic therapy for oral mucosa dysplasia in 9,10-dimethyl-1,2-benzanthracene-treated hamsters.

Abstract: The present study aimed to evaluate the efficacy of krypton laser photodynamic therapy (PDT) with PsD-007 for the treatment of oral mucosa dysplasia in 9,10-dimethyl-1,2-benzanthracene (DMBA)-treated hamsters. A DMBA-induced hamster cheek pouch model of precancerous lesions was created and the resultant 25 hamsters were divided into five groups. The right side was treated with PDT and the left side was used as the positive control. Following systemic anesthesia, an incision was made in the groin area to expose the femoral vein. PsD-007 was administered intravenously through the femoral vein. Various doses of photosensitizer were used to treat groups A-E. Subsequent to closing the incision, the right side of the buccal mucosa was irradiated with light using the krypton laser at a wavelength of 413 nm, a power density of 150 mW/cm2 and an irradiation time of 20 min. At six weeks post-surgery, the response was analyzed using histological examinations of the buccal pouch mucosa. A total of 24 hamsters completed the six-week observation period, as one hamster from group C died in the second week following the PDT. Of all 24 irradiated sides, 15 formed normal mucosal tissues and nine demonstrated mild dysplasia. Of the total control sides, six developed moderate dysplasia, five developed severe dysplasia and 13 progressed to carcinoma in situ or squamous cell carcinoma (SCC). The results revealed a significant difference between the two sides (P<0.01) and the various doses of the PsD-007 groups. When the PsD-007 dose was >10 mg/kg, there was no statistical difference (P>0.05). PsD-007-mediated krypton laser PDT is effective for the treatment of oral mucosa dysplasia in hamsters.

Shen|Lingyue|L| Xu|Qing|Q| Li|Pingping|P| Zhou|Guoyu|G|

krypton laser
photodynamic therapy
hamster
oral dysplasia