Modeling and performance analysis of movement-based group location management using RFID sensing in public transportation systems.
Location management, which consists of location registration and paging, is essential to provide mobile communication services to mobile stations (MSs). Since MSs riding on a public transportation system (TS) generates significant location registration signaling loads simultaneously when a TS with riding MSs moves between location areas (LAs), group location management was proposed. Under the group location management, an MS performs group registration when it gets on a TS and performs group deregistration when it gets off a TS. Then, only a TS updates its current location when it changes LA, on behalf of all riding MSs. In this paper, movement-based group location management using radio frequency identification (RFID) is proposed, where the MS's getting on and getting off behaviors are detected using RFID and only location update of a TS is carried out if the number of crossed cells from the last updated cell exceeds a predefined movement threshold, on behalf of all riding MSs. Then, we develop an analytical model for the performance analysis of the movement-based group location management and analyze the effects of various parameters on the performance. The results show that the movement-based group location management has reduced signaling cost compared with movement-based individual location management, and optimal performance can be achieved by choosing appropriate movement threshold values.


A Reappraisal of the Incidence of Placental Hydatidiform Mole Using Selective Molecular Genotyping.
Reports on the incidence of hydatidiform mole (HM) have varied depending on study population and methodology. This institutional-based study was undertaken to identify the incidence of HM in a modern obstetric practice using advanced laboratory diagnostic techniques. A retrospective review of consecutive hospital cases of HM was conducted for a 27-month period. Pathologic diagnoses of partial mole (PM) and complete mole (CM) were based on histopathologic assessment and selective use of p57 immunohistochemistry and molecular genotyping (MG) using formalin-fixed paraffin-embedded tissues. During the study period, 14,944 obstetric deliveries took place at our institution. Forty-nine cases of HM (18 CMs, 31 PMs) were identified. Histopathology with the selective use of p57 immunohistochemistry was used in 25 of 49 HMs (18 CMs, 7 PMs). Histopathologic features were equivocal in the remaining cases (24/49 cases), and adjunctive MG was performed; all were PMs. The incidence of HM was 3.3/1000 deliveries. Partial mole was more prevalent with a CM (PM ratio, 1:1.72). Our observed incidence of HM is greater than previous studies and is attributable to improved detection of PM cases. Molecular genotyping and cytogenetic evidence indicate that CM is almost half as common as PM. This ratio may be useful in benchmarking laboratory diagnosis and HM registries.


Maternal undernutrition and offspring sex determine birth-weight, postnatal development and meat characteristics in traditional swine breeds.
The aim of this study was to determine how maternal undernutrition during pregnancy and offspring birth-weight can affect the postnatal development of offspring under farm conditions, which may lead to consequences in its meat and carcass quality. The current study involved a total of 80 litters from Iberian sows fed a diet fulfilling daily requirements (n = 47; control) or providing 70% daily requirements (n = 33; underfed) from d 38 to d 90 of gestation when fetal tissue development begins. After birth, piglets born live were classified as low birth-weight (LBW; < 1 kg) and normal birth-weight (NBW; ≥1 kg). During the growing phase, 240 control and 230 underfed pigs (50% males and females) distributed by BW category and sex were studied until the slaughter. At birth and weaning, there were significant differences in all morphological measures and weight between NBW and LBW piglets as expected (P < 0.0005), but few effects of the gestational feed restriction. During the growing phase, NBW pigs continued with higher weight than LBW pigs on all the days of evaluation (P < 0.05), even though control-LBW-females and LBW-males showed a catch-up growth. However, underfed pigs showed slower growth and higher feed conversion ratio than control pigs (P < 0.0001) at 215 days old. Moreover, the average daily weight gain (ADWG) for the overall period was greater for NBW, male and control pigs than for their LBW, female and underfed pigs (P < 0.0001, P< 0.0005 and P< 0.05, respectively) and NBW pigs were slaughtered at a younger age than LBW pigs (P < 0.0001). After slaughtering, control pigs also had higher carcass yield and backfat depth than underfed pigs (P < 0.0005) and the maternal nutritional effect caused main changes in the polar lipid fraction of liver and loin. The fatty acid composition of loin in control pigs had higher C18:1n-9 and n-3 FA concentrations, as well as lower ∑n-6/∑n-3 ratio, than in underfed pigs (P < 0.005). In brief, results showed that the effects of maternal nutritional restriction appeared and increased with offspring age, causing worse developmental patterns for underfed pigs than for control pigs.


Diagnosis of brain death by transcranial Doppler sonography.
The blood flow velocities in the basal cerebral arteries can be recorded at any age by transcranial Doppler sonography. We examined nine children with either initial or developing clinical signs of brain death. Soon after successful resuscitation increased diastolic flow velocities indicated a probable decrease in cerebrovascular resistance; this was of no particular prognostic importance. As soon as there was a clinical deterioration, there was a reduction in flow velocities with retrograde flow during early diastole, probably due to an increase in cerebrovascular resistance; this indicated a doubtful prognosis. In eight of the nine children with clinical signs of brain death a typical reverberating flow pattern was found, which was characterised by a counterbalancing short forward flow in systole and a short retrograde flow in early diastole. This indicated arrest of cerebral blood flow. One newborn showed normal systolic and end diastolic flow velocities in the basal cerebral arteries for two days despite clinical and electroencephalographic signs of brain death. Shunting of blood through the circle of Willis without effective cerebral perfusion may explain this phenomenon. No patient had the typical reverberating flow pattern without being clinically brain dead. Transcranial Doppler sonography is a reliable technique, which can be used at the bedside for the confirmation or the exclusion of brain death in children in addition to the clinical examination.


Divergent selection for uterine capacity in rabbits. I. Genetic parameters and response to selection.
A 10-generation divergent selection experiment for uterine capacity (UC) measured as litter size in unilaterally ovariectomized females was carried out in rabbits. A total of 2,996 observations on uterine capacity of does (up to four parities) was recorded. Laparoscopy was performed at d 12 of their second gestation, and ovulation rate (OR) and number of implanted embryos (IE) were recorded in 735 does. Prenatal survival (PS) was assessed as UC/OR, embryo survival (ES) as IE/OR, and fetal survival (FS) as UC/IE. Genetic parameters and genetic trends were inferred using Bayesian methods. Marginal posterior distributions of all unknowns were estimated by Gibbs sampling. Heritabilities of UC, OR, IE, ES, FS, and PS were 0.11, 0.32, 0.22, 0.04, 0.14, and 0.09, respectively. Genetic and phenotypic correlations between FS and ES were low, suggesting different biological mechanisms for the two periods of survival. After 10 generations of selection, the divergence was approximately 1.5 rabbits, or approximately 1% per generation. Approximately one-half of this response was obtained in the first two generations of selection, which may suggest the presence of a major gene segregating in the base population.


Clinical and economic burden of bloodstream infections in critical care patients with central venous catheters.
Bloodstream infections (BSIs) complicate the management of intensive care unit (ICU) patients. We assessed the clinical and economic impact of BSI among patients of a managed care provider group who had a central venous catheter (CVC) placed in the ICU. We considered hospitalizations occurring between January 1, 2011, and September 30, 2014, that involved an ICU stay during which a CVC was placed. Comparisons were made between episodes where the patient did vs did not develop BSI after CVC insertion. Length of stay, costs of index hospitalization, and total costs over the 180 days after discharge were compared using linear mixed models. Inhospital mortality and 30-day readmission rates were compared using negative binomial regression models. Development of BSI was associated with longer hospital stay (+7 days), more than 3-fold increase in risk of inhospital death, and an additional $129 000 in costs for the index hospitalization. No statistically significant differences in 30-day readmission rates or costs of care over the 180-day period after discharge from the index admission were observed. Bloodstream infections after CVC placement in ICU patients are associated with significant increases in costs of care and risk of death during the index hospitalization but no differences in readmissions or costs after discharge.


Occurrence of p53 gene abnormalities in gastric carcinoma tumors and cell lines.
We explored the state of the p53 gene in gastric cancer. Using one or more methods, we examined 15 specimens from primary carcinomas (14 tumors, one cell line), five cell lines derived from metastases, and seven paired samples of nonmalignant gastric mucosa. Sequence analyses of complementary DNA containing the entire p53 gene open reading frame demonstrated abnormalities in one of five samples from primary tumors and in all five samples from metastases. The single cell line derived from a primary carcinoma had no abnormality of the gene. The six abnormalities included four point mutations, one base-pair deletion resulting in a frame shift, and a 24 base-pair deletion caused by an intronic point mutation (as determined by sequence analysis of genomic DNA). Four of the six mutations mapped to regions highly conserved among species or involved in simian virus 40 T-antigen binding. Restriction fragment length polymorphism studies confirmed that chromosome 17p allelic deletions occur only in a minority of primary tumors, but that they may occur more frequently in metastases. Northern blotting and ribonuclease protection assays detected only a fraction of the p53 gene abnormalities detected by sequencing. Our findings indicate that mutations of the p53 gene are relatively rare in primary gastric tumors but appear to be relatively frequent in cell lines derived from metastatic lesions. Our results may help in understanding the molecular events associated with progression and metastasis in gastric carcinoma.


Helicobacter pylori infection and expression of DNA mismatch repair proteins.
To determine the expression of DNA (MMR) proteins, including hMLH1 and hMSH2, in gastric epithelial cells in the patients with or without Helicobacter pylori (H pylori)-infected gastritis. Fifty H pylori-positive patients and 50 H pylori-negative patients were enrolled in the study. During endoscopy of patients with non-ulcer dyspepsia, two antral and two corpus biopsies were taken for histological examination (Giemsa stain) and for immunohistochemical staining of hMLH1 and hMSH2. The percentage of epithelial cell nuclei that demonstrated positivity for hMLH1 staining was 84.14 +/- 7.32% in H pylori-negative patients, while it was 73.34 +/- 10.10% in H pylori-positive patients (P < 0.0001). No significant difference was seen between the two groups regarding the percentage of epithelial cell nuclei that demonstrated positivity for hMSH2 staining (81.16 +/- 8.32% in H pylori-negative versus 78.24 +/- 8.71% in H pylori-positive patients; P = 0.09). This study indicates that H pylori might promote development of gastric carcinoma at least in part through its ability to affect the DNA MMR system.


Physiological and perceptual responses to walking while swinging hand-held towels.
The intent of this investigation was to determine the intensity of cardiovascular exercise produced by walking while swinging hand-held towels and its potential as a training method. Sixteen healthy college students were the volunteer subjects in this experiment. Each subject performed five randomly ordered trials in which they walked with: (1) a normal arm swing (NAS); (2) a vigorous arm swing (VAS); (3) a vigorous arm swing with hand-held towels (VAST); (4) a vigorous arm swing at NAS heart rate (VNH); and (5) a vigorous arm swing with hand-held towels at NAS heart rate (VTNH). Treadmill speed was 89 m.min-1 for VTNH, 103 for VNH, and 119 for NAS, VAS, and VAST trials. Each trial lasted 6 min and was separated by a 2 min walking recovery. Statistical analysis revealed (p < 0.05) that oxygen consumption (VO2), heart rate (HR), and rating of perceived exertion (RPE) were significantly greater for the VAST (27.8 +/- 3.9 ml.kg-1.min-1, 152 +/- 13.8 bpm, 4.2 +/- 1.4 Borg) vs. NAS (21.0 +/- 3.4, 125 +/- 14.7, 2.6 +/- 1.0) and VAS (24.7 +/- 3.7, 139 +/- 14.1, 3.4 +/- 1.1) vs. NAS trials, but were similar for NAS, VNH, and VTNH. Although not statistically significantly different, VO2, HR, and RPE were physiologically greater for the VAST than VAS trial. These results suggest that walking while swinging hand-held towels is a way to: (1) increase oxygen consumption without altering walking speed and (2) slow walking speed yet maintain exercise intensity.


Ethical questions in adolescent contraception.
Ethical problems often revolve around the conflicts of the models of beneficence and autonomy. Adolescents present a particular complication in their own struggle for autonomy. The physician is confronted with the further dilemma of sorting out the role of parents and the role of the adolescent patient in decision making. Furthermore, as adolescents develop their own moral code, they may lack consistency in their actions and opinions. The physician must examine the total context in arriving at a decision. The prescription of contraception is taken as an example of a common ethical dilemma.


Potential impact of antiretroviral chemoprophylaxis on HIV-1 transmission in resource-limited settings.
The potential impact of pre-exposure chemoprophylaxis (PrEP) on heterosexual transmission of HIV-1 infection in resource-limited settings is uncertain. A deterministic mathematical model was used to simulate the effects of antiretroviral PrEP on an HIV-1 epidemic in sub-Saharan Africa under different scenarios (optimistic, neutral and pessimistic) both with and without sexual disinhibition. Sensitivity analyses were used to evaluate the effect of uncertainty in input parameters on model output and included calculation of partial rank correlations and standardized rank regressions. In the scenario without sexual disinhibition after PrEP initiation, key parameters influencing infections prevented were effectiveness of PrEP (partial rank correlation coefficient (PRCC) = 0.94), PrEP discontinuation rate (PRCC = -0.94), level of coverage (PRCC = 0.92), and time to achieve target coverage (PRCC = -0.82). In the scenario with sexual disinhibition, PrEP effectiveness and the extent of sexual disinhibition had the greatest impact on prevention. An optimistic scenario of PrEP with 90% effectiveness and 75% coverage of the general population predicted a 74% decline in cumulative HIV-1 infections after 10 years, and a 28.8% decline with PrEP targeted to the highest risk groups (16% of the population). Even with a 100% increase in at-risk behavior from sexual disinhibition, a beneficial effect (23.4%-62.7% decrease in infections) was seen with 90% effective PrEP across a broad range of coverage (25%-75%). Similar disinhibition led to a rise in infections with lower effectiveness of PrEP (< or = 50%). Mathematical modeling supports the potential public health benefit of PrEP. Approximately 2.7 to 3.2 million new HIV-1 infections could be averted in southern sub-Saharan Africa over 10 years by targeting PrEP (having 90% effectiveness) to those at highest behavioral risk and by preventing sexual disinhibition. This benefit could be lost, however, by sexual disinhibition and by high PrEP discontinuation, especially with lower PrEP effectiveness (< or = 50%).


Resveratrol protects against L-arginine-induced acute necrotizing pancreatitis in mice by enhancing SIRT1-mediated deacetylation of p53 and heat shock factor 1.
Acute necrotizing pancreatitis (ANP) is a common severe critical illness with a high mortality rate. Resveratrol, a polyphenol compound derived from various plants such as grape skin, peanut, berry and veratrum, exhibits multiple biological activities, especially potent anti‑inflammatory activity, but its effect on ANP has not yet been fully elucidated. The present study aimed to investigate the effects of resveratrol on L-arginine-induced ANP and the possible mechanisms. A mouse model of ANP was established by 2 hourly intraperitoneal injections of 8% L-arginine (4 g/kg). Then the mice were treated by intragastric administration of resveratrol (80 mg/kg) every 12 h immediately after the second injection of L-arginine. Mice with ANP showed increased apoptosis of pancreatic acinar cells, pancreatic myeloperoxidase activity, serum lactate dehydrogenase activity, amylase, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) levels as well as decreased serum IL-10 level, pancreatic expression of heat shock factor 1 (HSF1), sirtuin 1 (SIRT1) and p53, but the ratio of acetylated HSF1 and p53 was markedly increased. Resveratrol enhanced the survival rate of mice with ANP from 47.8 to 71.4% and obviously restored the changes in mice with ANP as mentioned above. Additionally, interactions between SIRT1 and p53 and between SIRT1 and HSF1 in the pancreas of the mice were confirmed by co-immunoprecipitation. These data suggest that resveratrol protects against L-arginine-induced ANP, which may be related to the enhancement of SIRT1-mediated deacetylation of p53 and HSF1.


Adherens junctions and stem cells.
The specification, maintenance, division and differentiation of stem cells are integral to the development and homeostasis of many tissues. These stem cells often live in specialized anatomical areas, called niches. While niches can be complex, most involve cell-cell interactions that are mediated by adherens junctions. A diverse array of functions have been attributed to adherens junctions in stem cell biology. These include physical anchoring to the niche, control of proliferation and division orientation, regulation of signaling cascades and of differentiation. In this review, a number of model stem cell systems that highlight various functions of adherens junctions are discussed. In addition, a summary of the current understanding of adherens junction function in mammalian tissues and embryonic and induced pluripotent stem cells is provided. This analysis demonstrates that the roles of adherens junctions are surprisingly varied and integrated with both the anatomy and the physiology of the tissue.


Effects of chloropeptide on liver components and serum enzyme activities in mice.
The subcutaneous administration of chloropeptide, a hepatotoxic cyclic pentapeptide of Penicillium islandicum Sopp, induced a marked enlargement of hepatic weight in mice. Chemical analysis revealed an increment of water content. Biochemical investigation resulted in marked elevation of serum enzyme activities such as transaminases, alcohol dehydrogenase, fructose-1-phosphate aldolase and lactate dehydrogenase.


The value of repetition and reinforcement in improving oral hygiene performance.
The purpose of this study was to assess the value of including repetition and reinforcement in a dental health education program for school children. Sixty-one pupils, 11 to 13 years of age, were divided into three groups according to room assignments. Group I (control) received no oral hygiene lectures or instructions until the conclusion of the experiment. Group 2 (nonreinforced) received one lecture and a toothbrushing lesson, but no repetition or reinforcement. Group 3 (reinforced) received the same program as Group 2 on the initial visit and also received two additional visits for repetition and reinforcement of the lectures and instructions, plus a final summary lecture. Six visits were conducted at intervals of 0, 1, 5, 3, 8, 20 and 52 weeks, following a double-blind experimental format. PHP scores were obtained on all subjects on each of the six visits. It was concluded that the repetition and reinforcement components of this dental health education program were of significant value in improving the oral hygiene performance of the school children over a period of 1 year. The findings provide evidence of the desirability of incorporating these concepts in plaque-control program.


The effects of selective and non-selective inhibition of cyclo-oxygenase on frusemide-stimulated natriuresis.
The relative potency of four non-steroidal anti-inflammatory drugs (NSAIDs) - indomethacin, flurbiprofen, sulindac and piroxicam - in inhibiting frusemide-stimulated natriuresis and creatinine clearance was investigated in a placebo controlled cross-over study using healthy volunteers. All four drugs tested significantly inhibited the action of frusemide and they were equipotent in their effects. If it is accepted that sulindac is renal sparing with respect to inhibition of prostaglandin synthesis, our observations raise two possibilities concerning the underlying mechanism of antagonism: a) that inhibition of renal prostaglandin synthesis is not important; b) that sulindac interacts with frusemide in a manner different from other NSAIDs.


Determinants of the utilization of postpartum family visits: Evidence from rural areas of Eastern China.
Postpartum Family Visits (PFVs) have been advocated as a way to improve health outcomes for puerperal women and their newborns. This study aimed to identify individual factors associated with the utilization of PFVs in rural Jiangsu Province, China. We employed responses of the household survey in Jiangsu province, part of the National Health Service Survey (NHSS), a nationally representative survey in China. The data analysis framework was designed based on Andersen's behavioral model. The outcome variables included nonuse and deficient use of PFVs, and the explanatory variables were organized into three hierarchical levels: predisposing, enabling and need factors. Univariate analysis and multivariate logistic regression analysis were conducted to examine the impact of the three hierarchical levels on PFVs utilization. A total of 884 rural women who had a childbearing history in the prior five years answered PFVs questions. About 23.4% of them had never received any PFVs, and 40.4% received <3 visits. In the results of multivariate logistic regression, educational level (OR = 0.43, 95% CI: 0.24-0.77), income (OR = 0.62, 95% CI: 0.43-0.88), the distance from the nearest hospital (OR = 1.49, 95% CI: 1.07-2.07) and parity (OR = 2.17, 95% CI: 1.54-3.05) had significant relationship with nonuse. Factors significantly associated with deficient use of PFVs included employment (OR = 0.62, 95% CI: 0.39-0.98), the distance from the nearest hospital (OR = 1.73, 95% CI: 1.26-2.36), level of delivery institution (OR = 1.57, 95% CI: 1.14-2.17), and parity (OR = 1.45, 95% CI: 1.03-2.05). The study found lower Social Economic Status (SES), long distance with primary health institutions, and the increased need for services stemming from multi-parity reduced the likelihood of nonuse or deficient use of PFVs in rural areas. Multiparous, low SES women and those living far away from primary health institutions should be paid more attention to assure the coverage of postpartum care.


Aedes aegypti salivary gland extract alleviates acute itching by blocking TRPA1 channels.
Aedes aegypti (Ae. aegypti) saliva induces a variety of anti-inflammatory and immunomodulatory activities. Interestingly, although it is known that mosquito bites cause allergic reactions in sensitised hosts, the primary exposure of humans to Ae. aegypti does not evoke significant itching. Whether active components in the saliva of Ae. aegypti can counteract the normal itch reaction to injury produced by a histaminergic or non-histaminergic pathway in vertebrate hosts is unknown. This study investigated the effects of Ae. aegypti mosquito salivary gland extract (SGE) on sensitive reactions such as itching and associated skin inflammation. Acute pruritus and plasma extravasation were induced in mice by the intradermal injection of either compound 48/80 (C48/80), the Mas-related G protein-coupled receptor (Mrgpr) agonist chloroquine (CQ), or the transient receptor potential ankyrin 1 (TRPA1) agonist allyl isothiocyanate (AITC). The i.d. co-injection of Ae. aegypti SGE inhibited itching, plasma extravasation, and neutrophil influx evoked by C48/80, but it did not significantly affect mast cell degranulation in situ or in vitro. Additionally, SGE partially reduced CQ- and AITC-induced pruritus in vivo, suggesting that SGE affects pruriceptive nerve firing independently of the histaminergic pathway. Activation of TRPA1 significantly increased intracellular Ca2+ in TRPA-1-transfected HEK293t lineage, which was attenuated by SGE addition. We showed for the first time that Ae. aegypti SGE exerts anti-pruriceptive effects, which are partially regulated by the histamine-independent itch TRPA1 pathway. Thus, SGE may possess bioactive molecules with therapeutic potential for treating nonhistaminergic itch.


[Advances in digital twins technology of human skeletal muscle].
The human skeletal muscle drives skeletal movement through contraction. Embedding its functional information into the human morphological framework and constructing a digital twin of skeletal muscle for simulating physical and physiological functions of skeletal muscle are of great significance for the study of "virtual physiological humans". Based on relevant literature both domestically and internationally, this paper firstly summarizes the technical framework for constructing skeletal muscle digital twins, and then provides a review from five aspects including skeletal muscle digital twins modeling technology, skeletal muscle data collection technology, simulation analysis technology, simulation platform and human medical image database. On this basis, it is pointed out that further research is needed in areas such as skeletal muscle model generalization, accuracy improvement, and model coupling. The methods and means of constructing skeletal muscle digital twins summarized in the paper are expected to provide reference for researchers in this field, and the development direction pointed out can serve as the next focus of research.


Mitochondrial BK Channel Openers CGS7181 and CGS7184 Exhibit Cytotoxic Properties.
Potassium channel openers (KCOs) have been shown to play a role in cytoprotection through the activation of mitochondrial potassium channels. Recently, in several reports, a number of data has been described as off-target actions for KCOs. In the present study, we investigated the effects of BKCa channel openers CGS7181, CGS7184, NS1619, and NS004 in neuronal cells. For the purpose of this research, we used a rat brain, the mouse hippocampal HT22 cells, and the human astrocytoma U-87 MG cell line. We showed that CGS7184 activated the mitochondrial BKCa (mitoBKCa) channel in single-channel recordings performed on astrocytoma mitoplasts. Moreover, when applied to the rat brain homogenate or isolated rat brain mitochondria, CGS7184 increased the oxygen consumption rate, and can thus be considered a potentially cytoprotective agent. However, experiments on intact neuronal HT22 cells revealed that both CGS7181 and CGS7184 induced HT22 cell death in a concentration- and time-dependent manner. By contrast, we did not observe cell death when NS1619 or NS004 was applied. CGS7184 toxicity was not abolished by BKCa channel inhibitors, suggesting that the observed effects were independent of a BKCa-type channel activity. CGS7184 treatment resulted in an increase of cytoplasmic Ca2+ concentration that likely involved efflux from internal calcium stores and the activation of calpains (calcium-dependent proteases). The cytotoxic effect of the channel opener was partially reversed by a calpain inhibitor. Our data show that KCOs under study not only activate mitoBKCa channels from brain tissue, but also induce cell death when used in cellular models.


A classification system for mosquito life cycles: life cycle types for mosquitoes of the northeastern United States.
A system for the classification of mosquito life cycle types is presented for mosquito species found in the northeastern United States. Primary subdivisions include Univoltine Aedine, Multivoltine Aedine, Multivoltine Culex/Anopheles, and Unique Life Cycle Types. A montotypic subdivision groups life cycle types restricted to single species. The classification system recognizes 11 shared life cycle types and three that are limited to single species. Criteria for assignments include: 1) where the eggs are laid, 2) typical larval habitat, 3) number of generations per year, and 4) stage of the life cycle that overwinters. The 14 types in the northeast have been named for common model species. A list of species for each life cycle type is provided to serve as a teaching aid for students of mosquito biology.


Multiple breast cancer risk variants are associated with differential transcript isoform expression in tumors.
Genome-wide association studies have identified over 70 single-nucleotide polymorphisms (SNPs) associated with breast cancer. A subset of these SNPs are associated with quantitative expression of nearby genes, but the functional effects of the majority remain unknown. We hypothesized that some risk SNPs may regulate alternative splicing. Using RNA-sequencing data from breast tumors and germline genotypes from The Cancer Genome Atlas, we tested the association between each risk SNP genotype and exon-, exon-exon junction- or transcript-specific expression of nearby genes. Six SNPs were associated with differential transcript expression of seven nearby genes at FDR < 0.05 (BABAM1, DCLRE1B/PHTF1, PEX14, RAD51L1, SRGAP2D and STXBP4). We next developed a Bayesian approach to evaluate, for each SNP, the overlap between the signal of association with breast cancer and the signal of association with alternative splicing. At one locus (SRGAP2D), this method eliminated the possibility that the breast cancer risk and the alternate splicing event were due to the same causal SNP. Lastly, at two loci, we identified the likely causal SNP for the alternative splicing event, and at one, functionally validated the effect of that SNP on alternative splicing using a minigene reporter assay. Our results suggest that the regulation of differential transcript isoform expression is the functional mechanism of some breast cancer risk SNPs and that we can use these associations to identify causal SNPs, target genes and the specific transcripts that may mediate breast cancer risk.


Scavenger receptors: friend or foe in atherosclerosis?
Scavenger receptors were originally defined by their ability to bind and internalize modified lipoproteins. Nowadays the family of scavenger receptors is composed of structurally different surface receptors which recognize a broad pattern of common ligands which include, besides modified lipoproteins, apoptotic cells and pathogens. This review focuses on the role of scavenger receptors in the development of atherosclerotic lesions. Recent studies indicate that scavenger receptor A activity can be regulated by phosphorylation, glucosidases, 8-isoprostane, high glucose and nobiletin. Modulation of these regulatory components may beneficially influence scavenger receptor A's proatherogenic function. It appears that statins do lead to a reduction in CD36 transcription and could modulate in this way CD36-mediated atherosclerotic foam cell formation. Macrophage scavenger receptor BI appears to facilitate the development of small fatty streak lesions, whereas the formation of advanced atherosclerotic lesions is reduced, indicating a unique dual role for macrophage scavenger receptor BI in the pathogenesis of atherosclerosis. It is proposed that the presence of scavenger receptors in macrophages is beneficial because they remove potential deleterious material from the arterial wall. Inadequate handling of the internalized material by the macrophages will lead to foam cell formation. If adequate levels of ATP-binding cassette transporters and accepting HDL are present, however, the macrophage is perfectly able to metabolize and secrete the internalized atherogenic substances whereby HDL facilitates further transport from the arterial wall to the liver, leading to release in bile.


Differential proteomic analysis of renal cell carcinoma tissue interstitial fluid.
Renal cell carcinoma (RCC), the most common type of kidney cancer, currently has no biomarker of clinical utility. The present study utilized a mass spectrometry-based proteomics workflow for identifying differentially abundant proteins in RCC by harvesting shed and secreted proteins from the tumor microenvironment through sampling tissue interstitial fluid (TIF) from radical nephrectomies. Matched tumor and adjacent normal kidney (ANK) tissues were collected from 10 patients diagnosed with clear cell RCC. One-hundred thirty-eight proteins were identified with statistically significant differential abundances derived by spectral counting in tumor TIF when compared to ANK TIF. Among those proteins with elevated abundance in tumor TIF, nicotinamide n-methyltransferase (NNMT) and enolase 2 (ENO2) were verified by Western blot and selected reaction monitoring (SRM). The presence of ENO2 and thrombospondin-1 (TSP1) were verified as present and at elevated abundance in RCC patient serum samples as compared to a pooled standard control by enzyme-linked immunosorbent assay (ELISA), recapitulating the relative abundance increase in RCC as compared with ANK TIF.


Economic burden of severe asthma in Turkey: a cost of illness study from payer perspective.
Objective. To estimate economic burden of severe asthma in Turkey from payer perspective based on expert panel opinion on practice patterns in clinical practice. Methods. This cost of illness study was based on identification of per patient annual direct medical costs for the management of sever easthma in Turkey from payer perspective. Average per patient direct medical cost was calculated based on cost items related to outpatient visits, laboratory and radiological tests, hospitalizations and interventions, drug treatment and equipment, and co-morbidities/complications. Results. Based on total annual per patient costs calculated for outpatient admission ($ 177.91), laboratory and radiological tests ($ 82.32), hospitalizations/interventions ($ 1,154.55), drug treatment/equipment ($ 2,289.63) and co-morbidities ($ 665.39) cost items, total per patient annual direct medical costrelated to management of severe asthma was calculated to be $ 4,369.76 from payer perspective. Drug treatment/equipment (52.4%) was the main cost driver in the management of severe asthma in Turkey, as followed by hospitalizations/interventions (26.4%) and co-morbidities (15.2%). Conclusions. In conclusion, our findings indicate that managing patients with severe asthma pose a considerable burden to health economics in Turkey, with medications as the main cost driver.


Combining constitutive materials modeling with atomic force microscopy to understand the mechanical properties of living cells.
The goal of this work is to study the properties of living cells and cell membranes by using atomic force microscopy. During atomic force microscopy (AFM) measurement, there is a strong mechanical coupling between the AFM tip and the cell. The purpose of this paper is to present a model of the overall mechanical response of the cell that allows us to separate out the mechanical response of the cell from the local surface interactions we wish to quantify. These local interactions include recognition (or binding) events between molecules bound to an AFM tip (e.g., an antibody) and molecules or receptors on the cell surface (e.g., the respective antigen). The computational model differs from traditional Hertzian contact models by explicitly taking into account the mechanics of the biomembrane and cytoskeleton. The model also accounts for the mechanical response of the living cell during arbitrary deformation. The indentation of a bovine sperm cell is used to test the validity of this model, and further experiments are proposed to fully parameterize the model.


Construction and analysis of sample-specific driver modules for breast cancer.
It is important to understand the functional impact of somatic mutation and methylation aberration at an individual level to implement precision medicine. Recent studies have demonstrated that the perturbation of gene interaction networks can provide a fundamental link between genotype (or epigenotype) and phenotype. However, it is unclear how individual mutations affect the function of biological networks, especially for individual methylation aberration. To solve this, we provided a sample-specific driver module construction method using the 2-order network theory and hub-gene theory to identify individual perturbation networks driven by mutations or methylation aberrations. Our method integrated multi-omics of breast cancer, including genomics, transcriptomics, epigenomics and interactomics, and provided new insight into the synergistic collaboration between methylation and mutation at an individual level. A common driver pattern of breast cancer was identified from a novel perspective of a driver module, which is correlated to the occurrence and development of breast cancer. The constructed driver module reflects the survival prognosis and degree of malignancy among different subtypes of breast cancer. Additionally, subtype-specific driver modules were identified. This study explores the driver module of individual cancer, and contributes to a better understanding of the mechanism of breast cancer driven by the mutations and methylation variations from the point of view of the driver network. This work will help identify new therapeutic combinations of gene mutations and drugs in humans.


Congenital dacryocystocele: diagnosis using ante and post-natal ultrasonography.
Congenital dacryocystocele is an unusual type of nasolacrimal obstruction. Treatment with antibiotics or surgical removal is practiced to reduce the risks of infection (acute dacryocystitis) and potentially lethal septicemia. Here, we report a case of congenital dacryocystocele, antenatal ultrasonographic diagnosis (intrauterine), and postnatal reassessment.


Morbidity as a focus of preventive health care in the elderly.
The broad spectrum of preventive health concerns in the elderly ranges from incident disease to prevalent disease to the effect (sequelae) of disease. A major component of the burden of illness for the elderly derives from prevalent chronic disease. For a substantial impact on this burden, unique preventive health care strategies specific to the elderly need to be clearly formulated and tested. These strategies must include as a goal the prevention of disability and the maintenance of functioning. Current recommendations for periodic health examinations and for preventive health care for the elderly include only minimal components for a geriatric preventive health care approach. The specific content and impact of a full geriatric strategy is yet to be defined. A comprehensive geriatric periodic health examination will ultimately be based on epidemiologic definitions of the issues regarding risk factors, modifiers, and incident and prevalent disease as described above, melded with improved understanding of 1) the dynamics or models of illness in the elderly, 2) meaningful and important outcomes, 3) the points before which intervention will be most effective, and 4) further definition of the problems that contribute most to the burden of illness across the elderly population. The goals of prevention focused on prevalent disease will include attenuating the progression of morbidity, the development of disability, and the incidence of superimposed acute illness and injuries, and maximizing functional autonomy and quality of life in older persons. To accomplish these goals, epidemiology has major contributions to make in understanding the illness burden of an aging population, including 1) defining risk factors and effect modifiers for, and natural history of, disease and associated disability in older persons, 2) defining outcomes meaningful to older persons which express the burden of illness, and 3) identifying critical points before which intervention is efficacious in preventing disability.


Self-Medication Practices During the COVID-19 Pandemic Among the Adult Population in the Eastern Region of the Kingdom of Saudi Arabia.
Self-medication is vital to public health because it has an impact on people's health and the current healthcare system, both positively and negatively. During public health catastrophes like the COVID-19 disease, this is particularly true. This study aimed to examine the behavioral response of the community with regard to self-medication during the COVID-19 pandemic in the eastern region of the Kingdom of Saudi Arabia. During the COVID-19 outbreak from March to September 2020, a cross-sectional online survey of 398 participants using structured questionnaires was conducted to observe knowledge, prevalence, patterns, and sources of self-medication among the respondents in the eastern region of the Kingdom of Saudi Arabia. The percentage of respondents who had heard about self-medication was 50.5%, and those who practiced self-medication during COVID-19 were 43.7% of the respondents. Regarding knowledge, 60.3% had a low overall knowledge level versus 39.7% who had a high knowledge level. Most of those who practiced self-medication took medication based on their own decision (34.4%). The most frequently used drugs during the outbreak were analgesics (43.5%) and vitamins (24.9%). Only 1% of participants reported using anti-malaria drugs (hydroxychloroquine). The most common reasons for self-medication practices were having a mild illness (30.4%), followed by fear of infection (26.6%). The symptoms for which the respondents took self-medication were headache (29.6%), cough (26.6%), and fever (24.6%). Our investigation showed a low level of knowledge about self-medication and a considerable level of self-medication practices. Therefore, self-medication may be minimized with ongoing awareness-raising and sensitization.


Cross-Dehydrogenative Coupling of Heterocyclic Scaffolds with Unfunctionalized Aroyl Surrogates by Palladium(II) Catalyzed C(sp2)-H Aroylation through Organocatalytic Dioxygen Activation.
Cross-dehydrogenative coupling of biorelevant heterocyclic scaffolds with arylmethanes for aroylation during Pd(II)-catalyzed C(sp2)-H activation has been achieved through dioxygen activation by NHPI. Mass spectrometry and 1H NMR based kinetic isotope effect studies revealed C-H bond activation as the rate-determining step. Radical scavenging experiments indicated a radical pathway. The 1H NMR of an aliquot of reaction mixture and in situ trapping with 2-aminothiophenol revealed the formation of aldehyde during aerobic oxidation of the arylmethanes. The reaction has broad scope for different variations of the aroyl source and the directing group that includes benzothiazole, benzooxazole, pyridine, quinoxaline, pyrimidine, and azoarene. The benzylic methylene moiety was found to be the source of the aroyl carbon with the benzyl ether moiety being the most preferred followed by the carbonyl group of aryl aldehyde and the aryl methane. However, the ease of availability of aryl methanes makes them the most attractive as an aroyl source. A time dependent selective mono- and bis-aroylation can be achieved. The 1,3-diarylpyrimidines exhibited regioselective aroylation of the 2-phenyl moiety irrespective of the absence or presence of any substitutent (electron withdrawing or electron donating) in the 3-phenyl moiety. For unsymmetrical azoarenes, selective aroylation took place in the phenyl moiety bearing the substituent.


The effect of heat stress on gene expression and synthesis of heat-shock and milk proteins in bovine mammary epithelial cells.
In this study, bovine mammary epithelial cells were used to study stress responses after cells were exposed to 42°C for 0.5, 1, 3, 5, 8 or 12 h, and 38°C as control. The transcription of the genes (HSP27, HSP70 and HSP90) of heat shock protein (Hsp) was significantly enhanced under heat stress (HS). The peak transcription of HSP70 was 14 times the control at 1 h. Expression of proteins Hsp27 and Hsp70 was gradually increased under HS, with rapid deposition of Hsp70 in epithelial cells. The major milk protein genes of β-casein (CSN2) and butyrophilin (BTN1A1) were down-regulated and the synthesis of total caseins was decreased. After the cells were under HS (42°C) for 1 or 5 h, the cells were cultured at 38°C for 1, 6, 12 or 24 h for recovery. When the cells were cultured at 38°C for 24 h after HS for 1 h, the transcription of HSP70, HSP90, CSN2 and BTN reached normal levels. Our results suggest that HS initiated Hsp synthesis and decreased the milk protein synthesis. Hsp70 is extremely sensitive to HS and mainly responsible for mammary cell protection from HS.


Two protochordate genes encode pituitary adenylate cyclase-activating polypeptide and related family members.
To address the origin of the glucagon superfamily, we isolated and sequenced the complementary DNA and partial gene that encode pituitary adenylate cyclase-activating polypeptide (PACAP) from a protochordate (tunicate), a sister group of the amphioxus and vertebrates, but one that evolved before the amphioxus. This is the first report of any superfamily member sequenced from an invertebrate. Transcription of the tunicate pacap1 gene results in a messenger RNA that is 507 bp. The gene contains 3 exons that encode a signal peptide, GRF-like peptide(1-27), and PACAP(1-27). The tunicate GRF-like peptide has 59% identity with human GRF, whereas the deduced amino acids of tunicate PACAP(1-27) have 96% identity with the ovine, human, and salmon PACAP(1-27) forms. Another complementary DNA clone pacap2 was isolated and shown to contain 4 exons that encode a signal peptide, a cryptic peptide, and two peptides that are clearly members of the glucagon superfamily. One of the peptides has 89% sequence identity to the tunicate PACAP encoded in pacap1. A comparison of the two structurally related PACAP clones, each encoding two peptides on separate exons, shows high inter- and intraexon nucleotide sequence identity. Sequence analysis suggests that an exon duplication followed by a gene duplication was responsible for the origin of the two genes. It is argued that the PACAP gene is derived from the protochordate ancestral genes that led to the vertebrate forms of GRF and PACAP.


Polyoxometalate-Assisted, One-Pot Synthesis of a Pentakis[(triphenylphosphane)gold]ammonium(2+) Cation Containing Regular Trigonal-Bipyramidal Geometries of Five Bonds to Nitrogen.
Novel intercluster compounds consisting of pentakis[(triphenylphosphane)gold]ammonium(2+) cation (1) and Keggin polyoxometalate (POM) anions, i.e., {[Au(PPh3)]5(μ5-N)}3[α-PM12O40]2 (1-PW for M = W; 1-PMo for M = Mo), were synthesized in 30-36% yield by one-pot reaction of the protonic acid form of the Keggin POMs, H3[α-PM12O40]·nH2O (n = 13 for M = W; n = 15 for M = Mo) with monomeric (triphenylphosphane)gold(I) carboxylate [Au(RS-pyrrld)(PPh3)] [RS-Hpyrrld = (RS)-2-pyrrolidone-5-carboxylic acid] in the presence of aqueous NH3 at a molar ratio of 2:15:x (x = 3 for 1-PW; x = 7.5 for 1-PMo). These compounds resulted from the nitrogen-centered phosphanegold(I) clusterization of in situ generated monomeric phosphanegold(I) units, [Au(PPh3)]+ or [Au(L)(PPh3)]+ (L = NH3 or solvent), during the carboxylate elimination of [Au(RS-pyrrld)(PPh3)] in the presence of the Keggin POMs and aqueous NH3. The products 1-PW and 1-PMo were characterized by elemental analysis, Fourier transform infrared, thermogravimetric and differential thermal analyses (TGA/DTA), X-ray crystallography, and solid-state cross-polarization magic-angle-spinning (CPMAS) (31P and 15N) and solution (31P{1H} and 1H) NMR spectroscopy. The lattice contained three independent {[Au(PPh3)]5(μ5-N)}2+ cations, of which two took regular trigonal-bipyramidal (TBP) geometries and the third took a distorted, square-pyramidal (SP) geometry. These geometries are in contrast to those reported by Schmidbaur's group for {[Au(PPh3)]5(μ5-N)}2+ cations as BF4 salts. Density functional theory and ONIOM calculations for {[(L3P)Au]nN}(n-3)+ (L = H or Ph; n = 4-6) showed that the pentacoordinate cluster is energetically most stable and its TBP structure is only 1.6 kcal mol-1 more stable than its SP structure, in accordance with the experimental facts.


A Longitudinal Cohort to Monitor Malaria Infection Incidence during Mass Drug Administration in Southern Province, Zambia.
Rigorous evidence of effectiveness is needed to determine where and when to apply mass drug administration (MDA) or focal MDA (fMDA) as part of a malaria elimination strategy. The Zambia National Malaria Elimination Centre recently completed a community-randomized controlled trial in Southern Province to evaluate MDA and fMDA for transmission reduction. To assess the role of MDA and fMDA on infection incidence, we enrolled a longitudinal cohort for an 18-month period of data collection including monthly malaria parasite infection detection based on polymerase chain reaction and compared time to first infection and cumulative infection incidence outcomes across study arms using Cox proportional hazards and negative binomial models. A total of 2,026 individuals from 733 households were enrolled and completed sufficient follow-up for inclusion in analysis. Infection incidence declined dramatically across all study arms during the period of study, and MDA was associated with reduced risk of first infection (hazards ratio: 0.36; 95% CI: 0.16-0.80) and cumulative infection incidence during the first rainy season (first 5 months of follow-up) (incidence rate ratio: 0.34; 95% CI: 0.12-0.95). No significant effect was found for fMDA or for either arm over the full study period. Polymerase chain reaction infection status at baseline was strongly associated with follow-up infection. The short-term effects of MDA suggest it may be an impactful accelerator of transmission reduction in areas with high coverage of case management and vector control and should be considered as part of a malaria elimination strategy.


Energy metabolism and lysosomal events in hemorrhagic shock after aprotinin treatment.
Changes in activity of lysosomal enzymes and levels of adenine nucleotides were investigated during hemorrhagic hypotension and following recovery in rat kidneys. The effect of aprotinin pretreatment on these parameters was also tested, and the results were compared to saline-treated controls. Hemorrhagic hypotension led to a release of lysosomal enzymes and to extreme depletion of ATP. The pretreatment with aprotinin inhibits the changes in enzyme activities, but it has no effect on ATP loss during the hypotension. After reinfusion of the shed blood, however, the pretreated animals showed a faster rate of ATP regeneration. The results suggest an interaction between lysosomal enzyme release and ability of mitochondria to resynthetize high-energy compounds during the recovery period.


The role of evolutionarily conserved signalling systems in Echinococcus multilocularis development and host-parasite interaction.
Alveolar echinococcosis, one of the most serious and life-threatening zoonoses in the world, is caused by the metacestode larval stage of the fox-tapeworm Echinococcus multilocularis. Mostly due to its accessibility to in vitro cultivation, this parasite has recently evolved into an experimental model system to study larval cestode development and associated host-parasite interaction mechanisms. Respective advances include the establishment of axenic in vitro cultivation systems for parasite larvae as well as culture systems by which the early development of metacestode vesicles from totipotent parasite stem cells can be reconstituted under controlled laboratory conditions. A series of evolutionarily conserved signalling molecules of the insulin, epidermal growth factor and transforming growth factor-beta pathways that are able to functionally interact with corresponding host cytokines have been described in E. multilocularis and most likely play a crucial role in parasite development within the liver of the intermediate host. Furthermore, a whole genome sequencing project has been initiated by which a comprehensive picture on E. multilocularis cell-cell communication systems will be available in due time, including information on parasite cytokines that are secreted towards host tissue and thus might affect the immune response. In this article, an overview of our current picture on Echinococcus signalling systems will be given, and the potential to exploit these pathways as targets for anti-parasitic chemotherapy will be discussed.


Studies of the dynamics of biological macromolecules using Au nanoparticle-DNA artificial molecules.
The recent development of graphene liquid cells, a nanoscale version of liquid bubble wrap, is a breakthrough for in situ liquid phase electron microscopy (EM). Using ultrathin graphene sheets as the liquid sample container, graphene liquid cells have allowed the unprecedented atomic resolution observation of solution phase growth and dynamics of nanocrystals. Here we explore the potential of this technique to probe nanoscale structure and dynamics of biomolecules in situ, using artificial Au nanoparticle-DNA artificial molecules as model systems. The interactions of electrons with both the artificial molecules and the liquid environment have been demonstrated and discussed, revealing both the opportunities and challenges of using graphene liquid cell EM as a new method of bio-imaging.


Correlation between morphometrical parameters and disease-free survival in ductal breast cancer treated only by surgery.
A combination of quantitatively evaluated morphological parameters and of conventional prognostic indicators has been used to study 19 cases of invasive ductal breast carcinoma from patients treated only by surgery, later developing recurrences or metastases. This set of patients not treated with adjuvant therapy (radiotherapy, cytostatic or hormonal therapy), was selected from 350 consecutive breast cancers which had been treated with surgical therapy. The aim was to investigate whether the morphometrical features are correlated with disease-free survival. Of the single features, the mitotic activity index (MAI) is most strongly correlated with prognosis. Ten of the 19 patients had an MAI value above 9, and all of them recurred within 18 months. In contrast, of the 9 other patients with low mitotic rate (MAI below or equal to 9), none recurred within 24 months. Further, a correlation exists between disease-free survival, mean and standard deviation of nuclear and nucleolar area, and tubular component of the tumors. There is no correlation between nuclear form factors and recurrence. The multivariate prognostic score is also significantly correlated with recurrence, but not as strongly as in other publications. This is obviously due to the blurring influence of the lymph node status, which was not significantly correlated with the prognosis. Thus, in this small set of patients not treated with any adjuvant therapy, the results of morphometric analysis are in agreement with earlier data and emphasize the prognostic significance of quantitative microscopical analysis in breast cancer.


Does good trunk extensor performance protect against back-related work disability?
In this cohort study, dynamic trunk extensor performance was studied as a predictor of permanent work disability due to back disorders. As part of the comprehensive Mini-Finland Health Survey in 1978-80, the back muscle performance of 535 persons (267 men, 268 women) was measured using standardized repetitive arch-up and sit-up tests. At baseline, the participants were between 30 and 64 years of age. Retirements were followed for 12 years on average. During the follow-up, 56 subjects developed permanent work disability; 15 of these cases were back-related. Good dynamic trunk extensor performance was predictive of a decreased incidence of work disability due to chronic back disorders but not work disability due to other diseases. The risk of back-related work disability in the three highest quartiles in relation to the lowest quartile of dynamic trunk extension capacity was 0.28 (95% confidence interval, 0.09-0.94). Our study suggests that good dynamic trunk extension performance may protect against back-related permanent work disability.


[Chemical depletion of cumulative phosphorus in soils].
Cumulative phosphorus was defined as the phosphorus which was unavailable for plants and accumulated in soils fertilizer application. In this paper, chemical depletion of cumulative phosphorus in soils was studied by methods of batch equilibrium, kinetic, and anionic exchange resin membrane. The results showed that desorption amount of cumulative P increased with time increasing, and the desorption process was consonant with second-order kinetic equation. Release rate of P in different treatments was in order of PK > NPK > NK. The amount and rate of P released from red soil were higher than those of Fluvio-aquic soil. Desorbed P was significantly correlated with soil available P and P uptake by Plant. The maximum utilization of cumulative P in soils was about 45% of total phosphorus.


Role of Surgery in the Diagnosis and Management of Tuberculosis.
Modern thoracic surgery can now offer management of tuberculosis and its complications in selected patients with greater efficacy and less morbidity than ever before. Significantly, newer minimally invasive thoracic surgical approaches potentially lower thresholds for surgical candidacy, allowing more tuberculosis patients to receive operative treatment. This review aims to provide an overview of the role that modern thoracic surgery can play in diagnosing and managing patients with tuberculosis and its sequelae.


An Examination of Diet for the Maintenance of Remission in Inflammatory Bowel Disease.
Diet has been speculated to be a factor in the pathogenesis of inflammatory bowel disease and may be an important factor in managing disease symptoms. Patients manipulate their diet in attempt to control symptoms, often leading to the adoption of inappropriately restrictive diets, which places them at risk for nutritional complications. Health professionals struggle to provide evidence-based nutrition guidance to patients due to an overall lack of uniformity or clarity amongst research studies. Well-designed diet studies are urgently needed to create an enhanced understanding of the role diet plays in the management of inflammatory bowel disease. The aim of this review is to summarize the current data available on dietary management of inflammatory bowel disease and to demonstrate that dietary modulation may be an important consideration in managing disease. By addressing the relevance of diet in inflammatory bowel disease, health professionals are able to better support patients and collaborate with dietitians to improve nutrition therapy.


SEXUAL SELECTION AND MALE CHARACTERISTICS IN THE BLUEHEAD WRASSE, THALASSOMA BIFASCIATUM: MATING SITE ACQUISITION, MATING SITE DEFENSE, AND FEMALE CHOICE.
Through a series of replacement experiments with the bluehead wrasse, Thalassoma bifasciatum, we have identified male morphological characteristics that appear to be under phenotypic sexual selection. We were particularly interested in whether the various sources of sexual selection (male-male competition for unoccupied mating sites, defense of mating sites against small males, and female choice of males) were (1) independently associated with different phenotypic characteristics; (2) jointly affected the same characteristic in the same way; or (3) jointly affected the same characteristic in an antagonistic fashion. We replaced the resident large, brightly colored Terminal Phase (TP) males on a reef with the same number of TP males from other reefs. When transplanted, these males contest with each other to take over mating sites. The transplanted group of males were then scored for three components of fitness: (1) the quality of the site obtained through competition with other large males; (2) the male's ability to defend arriving females from small intruding males; and (3) changes in female visits to the site once the new male takes over. The first and second components are part of intrasexual selection; the third represents intersexual selection. We measured the opportunity for selection by partitioning variance in mating success, and measured the direct effects of sexual selection by estimating the covariance between morphology and fitness components. Opportunities for selection: Because females generally remain faithful to particular mating sites, most (54%) of the explainable variation in male mating success is due to the acquisition of a particular mating territory, which is the outcome of competition among TP males. There was less variation in mating success due to shifts in site use by females and defense of females against the intrusions of smaller males, but all components were significant. Effects of selection: Success in male-male competition among TP males, estimated by the quality of the territory acquired, was positively associated with body length and the relative length of the pectoral fin. Success in territorial defense against small males was primarily related to body length, with lesser contributions from body depth and the area of a white band on the flank. Contribution to fitness through female choice of males was positively associated with white band area. In the two instances where a character was associated with two fitness components, the direction of selection was the same. While body length was positively associated with winning intrasexual contests, it was not correlated to any behavioral measures of aggression. Similarly, the white band associated with attractiveness was not correlated with any aspect of courtship or aggression. Parasite load was uncorrelated with other morphological characters, and did not appear to affect any aspect of sexual selection. There was no evidence for stabilizing selection or significant additional contributions from second-order effects to the fitness surfaces. Fitness functions calculated using cubic splines were generally linear except for body length, which appeared sigmoid in its effect on site acquisition ability; this same feature tended to plateau in its effect on site defense. Analyses of the interactions of selection gradients with reef or experiment indicated that the effect of particular male characters on estimates of fitness was generally homogeneous in both time and space.


A Curvilinear Effect of Mental Workload on Mental Effort and Behavioral Adaptability: An Approach With the Pre-Ejection Period.
We tested Hancock and Szalma's mental workload model, which has never been experimentally validated at a global level with the measure of the pre-ejection period (PEP), an index of beta-adrenergic sympathetic impact. Operators adapt to mental workload. When mental workload level increases, behavioral and physiological adaptability intensifies to reduce the decline in performance. However, if the mental workload exceeds an intermediate level, behavioral and physiological adaptability will decrease to protect individuals from excessive perturbations. This decrease is associated with a change in behavioral strategies and disengagement. The experimental task was a modified Fitts' task used in Hancock and Caird. Five levels of task difficulty were computed. Behavioral and physiological adaptability was indexed by the performance with speed-accuracy trade-off and PEP reactivity. A curvilinear effect of task difficulty on PEP reactivity was significant, with high reactivity at the intermediate level but low reactivity at other levels. We observed a linear effect of task difficulty on error rate and a curvilinear effect on movement time. A decline in performance was noted up to the intermediate level, with a speed-accuracy trade-off above this level showing a faster movement time. We observed for the first time behavioral and physiological adaptability as a function of mental workload. The results have important implications for the modeling of mental workload, particularly in the context of the performance-sensitive domain (car driving and air traffic control). They can help guide the design of human-computer interaction to maximize adaptive behavior, that is, the "comfort zone."


2 ng/√Hz-resolution optomechanical accelerometer employing a three-dimensional MEMS interferometer.
A portable and high-resolution optomechanical accelerometer employing a deformable grating-based micro-electro-mechanical system (MEMS) interferometer is presented in this Letter. The movable reflective mirror of this interferometer is realized by a low-frequency vertical sensing structure with a three-dimensional (3D)-spring construction, which, to the best of our knowledge, is first proposed and fabricated in this work. All the components of the sensor are packaged in a metal case with a compact size of 4 cm×6 cm×3.15 cm. The micrometer-scale springs permit the device to have a high mechanical sensitivity of 893.23 µm/g and a resultant self-noise below 2 ng/H z from 2 to 7 Hz. Meanwhile, the measured voltage responsivity is as high as 15,874 V/g, demonstrating it is one of the most sensitive accelerometers reported to date.


Effect of methanol and water contents on production of biodiesel fuel from plant oil catalyzed by various lipases in a solvent-free system.
Methyl esters synthesized from plant oil and methanol by the methanolysis reaction are potentially important as a biodiesel fuel. The methanolysis of soybean oil by lipases from various microorganisms was investigated. Several of the lipases were found to catalyze methanolysis in a water-containing system without an organic solvent. The lipases from Candida rugosa, Pseudomonas cepacia, and Pseudomonas fluorescens displayed particularly high catalytic ability. The reaction rates of methanolysis catalyzed by the C. rugosa and P. fluorescens lipases decreased significantly when the water content was low, showing that water prevents the inactivation of these lipases by methanol. On the other hand, the methanolysis reaction rate catalyzed by the P. cepacia lipase remained high even under a low water content. In addition, the P. cepacia lipase gave high methyl ester contents in the reaction mixture up to 2 or 3 molar equivalents of methanol to oil, which is attributed to the P. cepacia lipase having substantial methanol resistance. For the same methanol content, the reaction rates of methanolysis catalyzed by the P. cepacia lipase increased with decreasing water content, and hence lipases strongly resistant to high methanol, such as that from P. cepacia, are desirable for use in methanolysis reaction processes.


Citrullination by peptidylarginine deiminase in rheumatoid arthritis.
Rheumatoid arthritis (RA) is a complex, multifactorial disease with genetic and immunological aspects. Because RA is an autoimmune condition, dysregulation of the immune system is implied. Many linkage and association studies have also indicated that multiple genetic factors are associated with RA. Although the contribution of each genetic factor is small, the combination of these factors affects RA development. Previous studies have suggested that genetic changes affect the internal immunological environment, which results in autoimmune diseases. More recent genetic studies indicate that the HLA-DRB gene is the predominant cause of RA and that other non-HLA genes are also involved. We reported that peptidylarginine deiminase (gene name abbreviated to PADI, protein name abbreviated to PAD) type 4 is the one of the non-HLA genetic factors involved in RA via citrullination. Antibodies against citrullinated proteins/peptides are highly specific to RA, but the physiological roles of PADI gene, PAD proteins as their products and citrullinated proteins/peptides are obscure. However, levels of anticitrullinated protein antibodies are apparently also increased and were involved in the pathogenesis of autoimmune arthritis in mice with collagen-induced arthritis (CIA). These data suggested that citrullinated protein and anticitrullinated protein antibodies play important roles in the development of RA. This review summarizes the relationship between RA and citrullination, as well as the role of PADI4 genetics.


Investigating the Et-1/SphK/S1P Pathway as a Novel Approach for the Prevention of Inflammation-Induced Preterm Birth.
Preterm birth (PTB), defined as birth before 37 completed weeks of gestation, occurs in up to 18 percent of births worldwide and accounts for the majority of perinatal morbidity and mortality. While the single most common cause of PTB has been identified as inflammation, safe and effective pharmacotherapy to prevent PTB has yet to be developed. Our group has used an in vivo model of inflammation-driven PTB, biochemical methods, pharmacological approaches, a novel endothelin receptor antagonist that we synthesized and RNA knockdown to help establish the role of endothelin-1 (ET-1) in inflammation-associated PTB. Further, we have used our in vivo model to test whether sphingosine kinase, which acts downstream of ET-1, plays a role in PTB. We have shown that levels of endothelin converting enzyme-1 (ECE-1) and ET-1 are increased when PTB is induced in timed pregnant mice with lipopolysaccharide (LPS) and that blocking ET-1 action, pharmacologically or using ECE-1 RNA silencing, rescues LPS-induced mice from PTB. ET-1 activates the sphingosine kinase/sphingosine-1-phosphate (SphK/S1P) pathway. S1P, in turn, is an important signaling molecule in the proinflammatory response. Interestingly, we have shown that SphK inhibition also prevents LPS-induced PTB in timed pregnant mice. Further, we showed that SphK inhibition suppresses the ECE-1/ET-1 axis, implicating positive feedback regulation of the SphK/S1P/ECE-1/ET-1 axis. The ET-1/SphK/SIP pathway is a potential pharmacotherapeutic target for the prevention of PTB.


Differential expression of genes in the subgranular zone and granular cell layer of the hippocampus after running.
Despite numerous studies, the mechanisms underlying the effects of exercise on brain function are not yet fully understood. Adult hippocampal neurogenesis is one of the most well-known effects of exercise on the brain, but its physiological roles during exercise are still ambiguous, mostly due to the difference in the structure and composition of each part of the hippocampus. In this study, we analyzed exercise-induced changes in gene expression in the subgranular zone (SGZ) and granular cell layer (GCL) of the hippocampus. Surprisingly, only about 10% of changes were common to both areas. Tollip expression, which is altered in the SGZ and in Engrailed-2 mutant mice following exercise, did not change in the GCL. Tollip levels were not changed in the whole hippocampus after two weeks of treadmill exercise, but immunofluorescence analysis showed that Tollip and Ki-67 co-localize in the hippocampal dentate gyrus . Through siRNA knockdown experiments, we found that levels of DCX and cellular survival rates were decreased in Tollip-deficient Neuro2A cells. Taken together, these results suggest a role for Tollip in mediating the beneficial effects of exercise, probably affecting cellular health in the SGZ of the hippocampus.


Case report: Systemic muscle involvement as the primary clinical manifestation of chronic active Epstein-Barr virus infection: A case-based review.
Chronic active Epstein-Barr virus infection (CAEBV) is common in Asian countries and characterized by recurrent or persistent infectious mononucleosis-like symptoms. Here, we describe a rare case of CAEBV-associated generalized myositis with extranodal NK/T-cell lymphoma, who initially presented with swelling and muscle soreness in the extremities and was diagnosed as polymyositis at the initial stage. CAEBV-associated generalized myositis is different from polymyositis and other types of myositis. Furthermore, it is prone to lymphoma with poor prognosis.


Synthesis, antifungal activity, and structure-activity relationships of coruscanone A analogues.
Coruscanone A, a plant-derived cyclopentenedione derivative, showed potent in vitro antifungal activity against Candida albicans and Cryptococcus neoformans comparable to amphotericin B and fluconazole. A series of analogues have been synthesized by modification of the cyclopentenedione ring, the enolic methoxy functionality, and the side chain styryl moiety of this natural product lead. A structurally close 1,4-benzoquinone analogue was also prepared. All the compounds were examined for their in vitro activity against major opportunistic fungal pathogens including C. albicans, C. neoformans, and Aspergillus fumigatus and fluconazole-resistant C. albicans strains, with several analogues demonstrating potent antifungal activity. Structure-activity relationship studies indicate that the 2-methoxymethylenecyclopent-4-ene-1,3-dione structural moiety is the pharmacophore responsible for the antifungal activity of this class of compounds while the side chain styryl-like moiety plays an important complementary role, presumably contributing to target binding.


Golgi-localized STELLO proteins regulate the assembly and trafficking of cellulose synthase complexes in Arabidopsis.
As the most abundant biopolymer on Earth, cellulose is a key structural component of the plant cell wall. Cellulose is produced at the plasma membrane by cellulose synthase (CesA) complexes (CSCs), which are assembled in the endomembrane system and trafficked to the plasma membrane. While several proteins that affect CesA activity have been identified, components that regulate CSC assembly and trafficking remain unknown. Here we show that STELLO1 and 2 are Golgi-localized proteins that can interact with CesAs and control cellulose quantity. In the absence of STELLO function, the spatial distribution within the Golgi, secretion and activity of the CSCs are impaired indicating a central role of the STELLO proteins in CSC assembly. Point mutations in the predicted catalytic domains of the STELLO proteins indicate that they are glycosyltransferases facing the Golgi lumen. Hence, we have uncovered proteins that regulate CSC assembly in the plant Golgi apparatus.


Prevalence and natural course of ectopic atrial tachycardia.
The purpose of this study was to calculate the prevalence of ectopic atrial tachycardia in a population of young asymptomatic males and to assess its natural course both in asymptomatic subjects and in symptomatic hospital patients. 12-lead electrocardiograms (ECG) of 3554 consecutive males applying for a pilot's licence were analysed. ECGs of symptomatic arrhythmia patients at two university hospitals were also analysed. A repeat ECG was taken in cases of ectopic atrial tachycardia to assess the natural course of this arrhythmia. Twelve out of 3554 asymptomatic subjects (prevalence 0.34%) and 17 out of 3700 symptomatic arrhythmia patients (prevalence 0.46%) had ECG evidence of ectopic atrial tachycardia. A repeat ECG was obtained after a mean follow-up of 8+/-3 years in asymptomatic subjects and 7+/-3 years in symptomatic patients. After the follow-up, seven (26%) out of 27 patients were still in a similar ectopic atrial rhythm, 10 (37%) showed a change in P wave morphology and 10 (37%) were in sinus rhythm. Heart rate was significantly slower (mean rate 81+/-19 vs 109+/-17 beats. min-1) in the repeat ECGs. Asymptomatic ectopic atrial tachycardia is not an uncommon finding in a population of young males. The majority of patients show slowing of heart rate in the course of time, either with restoration of sinus rhythm or with a change in P wave morphology, suggesting that the ectopic foci undergo gradual degeneration with time.


Single vibronic level emission spectroscopic studies of the ground state energy levels and molecular structures of jet-cooled HGeBr, DGeBr, HGeI, and DGeI.
Single vibronic level dispersed fluorescence spectra of jet-cooled HGeBr, DGeBr, HGeI, and DGeI have been obtained by laser excitation of selected bands of the A (1)A(")-X (1)A(') electronic transition. The measured ground state vibrational intervals were assigned and fitted to anharmonicity expressions, which allowed the harmonic frequencies to be determined for both isotopomers. In some cases, lack of a suitable range of emission data necessitated that some of the anharmonicity constants and vibrational frequencies be estimated from those of HGeClDGeCl and the corresponding silylenes (HSiX). Harmonic force fields were obtained for both molecules, although only four of the six force constants could be determined. The ground state effective rotational constants and force field data were combined to calculate average (r(z)) and approximate equilibrium (r(e) (z)) structures. For HGeBr r(e) (z)(GeH)=1.593(9) A, r(e) (z)(GeBr)=2.325(21) A, and the bond angle was fixed at our CCSD(T)/aug-cc-pVTZ ab initio value of 93.6 degrees . For HGeI we obtained r(e) (z)(GeH)=1.589(1) A, r(e) (z)(GeI)=2.525(5) A, and bond angle=93.2 degrees . Franck-Condon simulations of the emission spectra using ab initio Cartesian displacement coordinates reproduce the observed intensity distributions satisfactorily. The trends in structural parameters in the halogermylenes and halosilylenes can be readily understood based on the electronegativity of the halogen substituent.


The evolving nature of weight dissatisfaction and eating behaviors among men: Secular trends among college men across four decades.
Research supports increasing cultural pressures for leanness among young men; however, few studies have examined whether weight dissatisfaction or efforts to alter weight have become more prevalent for men over time. The present study evaluated secular trends in weight dissatisfaction and related behaviors among college-age men across 4 decades; 1,097 men completed surveys while they were in college in 1982 (n = 276), 1992, (n = 233), 2002 (n = 241), and 2012 (n = 347). In 1982, men with a body mass index (BMI) between 18.5 and 25 kg/m2 were more likely to describe themselves as being overweight compared with men in all other cohorts, whereas in 1992, 2002, and 2012, men with a BMI between 18.5 and 25 kg/m2 were more likely to describe themselves as underweight compared with men in all other cohorts. Overall, 57-62% of men reported weight dissatisfaction, although there were no significant differences in the proportion of men wanting to lose, maintain, or gain weight across cohorts. There was no significant difference in the amount of weight gain desired across cohorts despite increasing BMI from 1982 to subsequent cohorts; however, desired BMI and endorsement of fad diets differed across cohorts, with higher desired BMI in 1992 and 2002 and high-protein diets being the most common in 2012. These results suggest that weight dissatisfaction has remained substantial and relatively stable among young men over time. Trends relating to weight perception, dieting, and exercise are consistent with an increasing focus on leanness and muscularity for men in recent years. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


Novel heteronuclear methods of assignment transfer from a diamagnetic to a paramagnetic protein: application to rat cytochrome b5.
15N and 1H resonance assignments for backbone and side-chain resonances of both equilibrium forms of rat ferricytochrome b5 have been obtained, using a combination of novel heteronuclear assignment transfer methods from the known assignments of the diamagnetic protein [Guiles, R. D., Basus, V. J., Kuntz, I. D., & Waskell, L. A. (1992) Biochemistry 31, 11365-11375] and computational methods which depend on an accurate determination of the orientation of the components of the susceptibility tensor. The transfer of amide proton resonance assignments takes advantage of the apparent insensitivity of amide 15N resonances to pseudocontact effects, evident in overlays of 15N-1H heteronuclear correlation spectra. Amide-proton resonance assignments tentatively transferred from the known diamagnetic assignments to the paramagnetic form of the protein were confirmed using conventional assignment strategies employing 600-MHz COSY, HOHAHA, and NOESY spectra of the oxidized protein. As was observed in rat ferrocytochrome b5, more than 40% of all residues exhibited NMR detectable heterogeneity due to the two different orientations of the heme. Complete assignment of both forms enabled accurate determination of the orientation of the susceptibility tensor for both conformations of the heme. The orientation of the z-component of the susceptibility tensors for the two forms are indistinguishable, while the in-plane components appear to differ by about 6 degrees. Differences in the orientation of the in-plane susceptibility components are undoubtedly due dominantly to the relative axial rotation of the heme of between 5 degrees and 10 degrees indicated by the NOESY contacts to the protein observed in the spectra of the ferrocytochrome [Guiles, R. D., Basus, V. J., Kuntz, I. D., & Waskell, L. A. (1992) Biochemistry 31, 11365-11375; Pochapsky, T. C., Sligar, S. G., McLachlan, S. J., & LaMar, G. N. (1990) J. Am. Chem. Soc. 112, 5258-5263].


A Western Australian kindred with Dutch cerebral amyloid angiopathy.
A family from the south of Western Australia is described with Dutch cerebral amyloid angiopathy (HCHWA-D). The proband died at age 60 from recurrent lobar haemorrhages in the brain, as did his sister and five other family members. The APP 693 mutation at position 22 of the Abetapeptide resulting in a glutamine for glutamic acid was identified in the proband and the affected sister. Pathologically lobar haemorrhages were found with cerebrovascular angiopathy; neuritic plaques were found but no neurofibrilary tangles. There was a leukoencephalopathy on MRI scanning. Dementia and cognitive decline has not been observed in this family. This is the first family reported outside of Europe and the Northern Hemisphere. The discovery highlights the importance of detecting this rare cause of fatal cerebral haemorrhage as it has implications for gene testing and general medical management.


[Sequential spontaneous coronary artery dissection in a female patient on oral ephedrine].
Spontaneous coronary artery dissection (SCAD) is an infrequent, but not rare, cause of acute coronary syndrome. It mainly affects young women, often with few or no traditional cardiovascular risk factors. In the case described, a 57-year-old woman experienced a first episode of SCAD involving a distal branch of the circumflex coronary artery--treated conservatively--followed, after a few hours, by a second episode of SCAD involving the left anterior descending coronary artery, complicated by hemodynamic instability and treated with emergency angioplasty. During the previous months, the patient was taking a slimming drug containing ephedrine. Dual spontaneous coronary dissection of different type and involving two different vessels, which occurred in the same patient within a few hours, testifies the heterogeneity of the clinical picture of this syndrome and of the therapeutic approach.


5-Selenocyanatouracil: A Potential Hypoxic Radiosensitizer. Electron Attachment Induced Formation of Selenium Centered Radical.
The propensity of 5-selenocyanatouracil (SeCNU) to decomposition induced by attachment of electron was scrutinized with the G3B3 composite quantum-chemical method and radiolytic studies. Favorable thermodynamic (Gibbs free reaction energy of -13.65 kcal/mol) and kinetic (Gibbs free activation energy of 1.22 kcal/mol) characteristics revealed by the G3B3 free energy profile suggest SeCNU to be sensitive to electron attachment. The title compound was synthesized in the reaction between uracil and selenocyanogen chloride in acetic acid. Then, an aqueous and deoxygenated solution of the HPLC purified compound containing tert-butanol as a hydroxyl radical scavenger was irradiated with X-rays. SeCNU radio-degradation results in two major products: the U-Se-Se-U dimer and the adduct of the ●OtBu radical to the U-Se● radical, U-Se-OtBu. The effects of radiolysis as well as the results of G3B3 calculations point to U-Se● as the primary product of dissociative electron attachment to SeCNU. The MTT test shows that SeCNU is nontoxic in vitro in concentrations equal to or lower than 10-6 M. Ionizing radiation will probably induce cytotoxic intra- and interstrand DNA cross-links as well as protein-DNA cross-links in the genomic DNA labeled with SeCNU.


Therapeutic treatment of systemic candidiasis in newborns.
This report details the management of a group of newborns who had a diagnosis of systemic Candida albicans septicemia. All the infants were extremely preterm (29 weeks' gestation or less) and had predisposing factors to disseminated fungal infections. Diagnosis was made by cultures from blood, urine, and from the tip of indwelling catheters. Therapy was based in all the infants on the combination of amphotericin B (Amph. B) and 5-fluorocytosine (5FC). Amph. B was intravenously administrated at a test dose of 0.1 mg/kg which if tolerated, was increased with scalar doses until a maximum of 0.35-0.50 mg/kg/die. 5FC was intravenously or orally administered at a 100-200 mg/kg/die dose. Time of treatment with Amph B was prolonged from 13 to 30 days and that with 5FC from 11 to 40 days. In two infants there was an increase of transaminases and Gamma GT and no infant had signs of nephrotoxicity. The high therapeutic success (75% of cases) confirms the validity of the utilized therapeutic schemes.


A two-dimensional, finite element analysis of vasogenic brain edema.
The authors constructed a two-dimensional model of vasogenic brain edema, using the finite element method (FEM). The model incorporates the following physical parameters: cerebrovascular hydraulic conductivity, metabolic water production, tissue hydraulic conductivity and compliance, tissue and plasma osmotic and hydrostatic pressures, cerebrospinal fluid hydrostatic pressure and absorption, intracerebral stress, and shift of brain tissue. These parameters, related by partial differential equations, were approximated numerically in time and space by the FEM. The results of computer simulation of brain edema by the FEM were compared with experimental data obtained in a feline cold injury brain edema model. Computer simulation predicted the changes observed in interstitial pressure, extent of edema, intracerebral stress distribution, and shift of brain tissue. The results indicate that the FEM, applied to a model of vasogenic brain edema, can be used to predict the time course and regional distribution of fluid accumulation and the accompanying regional stress and deformation of brain tissue.


Expression of Pluripotency Markers in Nonpluripotent Human Neural Stem and Progenitor Cells.
Nonpluripotent neural progenitor cells (NPCs) derived from the human fetal central nervous system were found to express a number of messenger RNA (mRNA) species associated with pluripotency, such as NANOG, REX1, and OCT4. The expression was restricted to small subpopulations of NPCs. In contrast to pluripotent stem cells, there was no coexpression of the pluripotency-associated genes studied. Although the expression of these genes rapidly declined during the in vitro differentiation of NPCs, we found no evidence that the discrete expression was associated with the markers of multipotent neural stem cells (CD133+/CD24lo), the capacity of sphere formation, or high cell proliferation rates. The rate of cell death among NPCs expressing pluripotency-associated genes was also similar to that of other NPCs. Live cell imaging showed that NANOG- and REX1-expressing NPCs continuously changed morphology, as did the nonexpressing cells. Depletion experiments showed that after the complete removal of the subpopulations of NANOG- and REX1-expressing NPCs, the expression of these genes appeared in other NPCs within a few days. The percentage of NANOG- and REX1-expressing cells returned to that observed before depletion. Our results are best explained by a model in which there is stochastic transient expression of pluripotency-associated genes in proliferating NPCs.


Tumor-Microenvironment-Induced All-in-One Nanoplatform for Multimodal Imaging-Guided Chemical and Photothermal Therapy of Cancer.
Precisely locating tumor site based on tumor-microenvironment-induced (TMI) multimodal imaging is especially interesting for accurate and efficient cancer therapy. In the present investigation, a novel TMI all-in-one nanoplatform, CuSNC@DOX@MnO2-NS, has been successfully fabricated for chemical and photothermal (Chem-PTT) therapy guided by multimodal imaging on tumor site. Here, the CuS nanocages with mesoporous and hollow structure (CuSNC) acting as nanocarriers provide high capacity for loading the anticancer drug, doxorubicin (DOX). The outer layer of the MnO2 nanoshell (MnO2-NS) acts as "gatekeeper" to control the DOX release until the nanoplatform arrives at the tumor site, where abundant glutathione and H+ decompose MnO2-NS into paramagnetic Mn2+. The magnetic resonance imaging and fluorescent imaging were then triggered to locate the tumor, which was further improved by photothermal imaging on account of the intrinsic property of CuSNC. Guided by the multimode imaging, the combination of chemical therapy upon DOX and photothermal therapy upon CuSNC exhibits eminent efficiency on tumor ablation. The nanoplatform exhibits biocompatibility to avoid unwanted harm to normal tissues during trans-shipment in the body. The investigation thus develops a cost-effective TMI nanoplatform with facile preparations and easy integration of Chem-PTT treatment capabilities guided by multimodal imaging for potential application in precise therapy.


[Influence of silica on intestinal absorption of solid self-microemulsifying drug delivery systems].
Solid carriers had important effects on the properties of solid self-microemulsifying drug delivery systems (S-SMEDDS). In order to make the basis for further development of S-SMEDDS, the influences of silica on the absorption of S-SMEDDS were investigated. An in vitro lipolysis model was used to evaluate the influence of silica on self-microemulsifying drug delivery system digestion from intestinal tract. S-SMEDDS containing silica were prepared by extrusion/spheronization. The drug release and absorption were investigated. The results showed that lipolysis rate and drug concentration in aqueous phase after intestinal lipolysis both increased by adding silica, which was benefit to drug absorption. And silica was not benefit to absorption for slowing drug release. Consistently, there was no significant influence of silica on intestinal absorption. This study implied that the influences of silica on lipolysis rate and drug release were both amount dependent and it is suggested that silica could be used as the solid carrier but the proportion needs to be optimized.


The proof's in the partnerships: Are Affordable Care Act and Local Health Department accreditation practices influencing collaborative partnerships in community health assessment and improvement planning?
The strengthened requirement for nonprofit hospitals to complete a community health needs assessment and implementation plan in the Affordable Care Act, concurrent with a new voluntary accreditation process for local health departments that requires collaborative community health assessments and community health improvement plans, have led to a resurgence of interest in assessment and improvement planning. This study provides baseline data that will help determine whether the Affordable Care Act and public health accreditation will result in more collaborative community assessment and community health improvement activity by describing trends in collaborative community health assessment and community health improvement plan activities. Data sources include the National Profile of Local Health Departments studies and a database of community health assessment, community health needs assessment, community health improvement plan, and other implementation planning reports from across the country. The study finds that collaborative community assessment activity is positively associated with population size, governance type, and local health department and coalition-led efforts.


Identification of fungus-responsive cis-acting element in the promoter of Brassica juncea chitinase gene, BjCHI1.
Chitinases are a group of pathogenesis-related proteins. The Brassica juncea chitinase gene BjCHI1 is highly inducible by pathogenic fungal infection, suggesting that the promoter of BjCHI1 might contain specific cis-acting element responsive to fungal attack. To identify the fungus-responsive element in BjCHI1 promoter (BjC-P), a series of binary plant transformation vectors were constructed by fusing the BjC-P or its deletion-derivatives to β-glucuronidase (GUS) reporter gene. Expression of the GUS reporter gene was systematically assayed by a transient gene expression system in Nicotiana benthamiana leaves treated with fungal elicitor Hexa-N-Acetyl-Chitohexaose, as well as in transgenic Arabidopsis plants inoculated with fungus Botrytis cinerea. The histochemical and quantitative GUS assays showed that the W-box-like element (GTAGTGACTCAT) in the region (-668 to -657) was necessary for the fungus-response, although there were another five W-box-like elements in BjC-P. In addition, gain-of-function analysis demonstrated that the fragment (-409 to -337) coupled to the W-box-like element was needed for full magnitude of the fungal induction. These results revealed the existence of a novel regulation mechanism of W-box-like element involved in plant pathogenic resistance, and will benefit the potential application of BjC-P in engineering crops.


A randomized DBPC trial to determine the optimal effective and safe dose of a SLIT-birch pollen extract for the treatment of allergic rhinitis: results of a phase II study.
Sublingual immunotherapy (SLIT) is a potential efficacious and safe treatment option for patients with respiratory, IgE-mediated allergic diseases. A combined tolerability, dose-finding study with a sublingual liquid birch pollen preparation (SB) was conducted. Two hundred and sixty-nine adults with birch-pollen-induced AR were randomized to placebo, SB: 3333, 10,000, 20,000 or 40,000 AUN/ml. Differences in symptom scores following a titrated nasal provocation test (TNPT) at baseline and after 5 months of treatment were determined. Safety, tolerability, birch-pollen-specific immunoglobulin levels and peak nasal inspiratory flow (PNIF) were also measured (all measures determined outside the birch pollen season). In all treatment groups, an improvement in symptom scores after treatment compared to baseline was observed, with an additional stepwise improvement in the active groups compared to placebo, which was significant in high-dose groups (P = 0.008 and P < 0.001, respectively). For this primary endpoint, a significant linear dose-response curve was observed: the higher the dose, the better the improvement observed. Likewise, active treatment resulted in an increase in PNIF and serum IgG levels compared to placebo. The highest improvements were found in the 40,000 AUN/ml group. All active dosages resulted in more adverse reactions than placebo, which were mainly mild and well-controlled. A multicentre trial evaluated the dose-response and tolerability of SB. All active treatment groups showed better responses than placebo for both primary and secondary parameters. The results indicate that, within the studied dose range, SB 40,000 AUN/ml is the most optimal effective and safe dose (ClinicalTrials.gov: NCT01639768).


Paget's disease of bone.
Paget's disease is a common disorder of bone of presumed viral aetiology which, in a minority of patients, may cause severe symptoms. Both calcitonin and the diphosphonates have specific anti-pagetic effects. Newer diphosphonates, unlike etidronate, do not impair mineralization, and when they become available these will be the drugs of choice. Until that time, both calcitonin and etidronate continue to have a useful place in the management of this disorder.


Improved performance of ELISAs for fertility assessment using common reagents and assay protocol as evidence from quality control studies.
At our Institute, a panel of reproductive hormones, viz., estrone glucuronide (E1G), pregnanediol glucuronide (PdG), luteinising hormone (LH), and follicle stimulating hormone (FSH) are estimated by ELISA for the assessment of fertility from a single urine sample collected from a subject. In order to make the estimates less cumbersome, the selection and mode of presentation of immunoreagents of the assay were modified in such a way that, either on reconstitution or single dilution, would result in ready-to-use reagents in the assay. Retrospective analysis on the performance of these ELISAs with uniform protocols (n = 86) was compared with assays having individual assay protocols (n = 116). The performance of the assay, based on the standard curve characteristics and quality control pools, was better and the rate of acceptance of these assays improved from 87.9 to 97.6%. The simplification of assay protocols, thus, had better impact on the quality and reproducibility of immunoassay of the four analytes.