A Molecular Assay to Quantify Male and Female Plasmodium falciparum Gametocytes: Results From 2 Randomized Controlled Trials Using Primaquine for Gametocyte Clearance.
Single low-dose primaquine (PQ) reduces Plasmodium falciparum infectivity before it impacts gametocyte density. Here, we examined the effect of PQ on gametocyte sex ratio as a possible explanation for this early sterilizing effect. Quantitative reverse-transcription polymerase chain reaction assays were developed to quantify female gametocytes (targeting Pfs25 messenger RNA [mRNA]) and male gametocytes (targeting Pf3D7_1469900 mRNA) in 2 randomized trials in Kenya and Mali, comparing dihydroartemisinin-piperaquine (DP) alone to DP with PQ. Gametocyte sex ratio was examined in relation to time since treatment and infectivity to mosquitoes. In Kenya, the median proportion of male gametocytes was 0.33 at baseline. Seven days after treatment, gametocyte density was significantly reduced in the DP-PQ arm relative to the DP arm (females: 0.05% [interquartile range {IQR}, 0.0-0.7%] of baseline; males: 3.4% [IQR, 0.4%-32.9%] of baseline; P < .001). Twenty-four hours after treatment, gametocyte sex ratio became male-biased and was not significantly different between the DP and DP-PQ groups. In Mali, there was no significant difference in sex ratio between the DP and DP-PQ groups (>0.125 mg/kg) 48 hours after treatment, and gametocyte sex ratio was not associated with mosquito infection rates. The early sterilizing effects of PQ may not be explained by the preferential clearance of male gametocytes and may be due to an effect on gametocyte fitness.


Review article: targeted screening for hereditary haemochromatosis in high-risk groups.
Patients with hereditary haemochromatosis are at risk for significant morbidity from iron overload as well as reduced life-expectancy once cirrhosis is established. Although inexpensive, sensitive screening tests and effective therapy are available, there is continued debate regarding the utility of screening for this condition because of recent data suggesting that the homozygous haemochromatosis mutation (C282Y) is associated with low penetrance and mild expressivity when identified in population screening studies. In this review, we examine the published data related to general population screening for haemochromatosis, as well as the evidence for screening selected 'high-risk' populations. We also suggest possible screening strategies based on the available evidence.


[Environmental impact assessment based on planning support system].
How to assess environmental impact is one of the keys in land use planning. This article described in detail the concepts of activities, impact zones, functions, and sensitivities, as well as the development of STEPP (strategic tool for integrating environmental aspects in planning procedures) based on Avenue, the secondary developing language of ArcView GIS. The system makes it convenient for planning practitioners exchanging information, and can spatially, visually and quantitatively describe environmental impact and its change. In this study, the urban-rural combination area located between EDE and Veenendaal of The Netherlands was taken as case, and the results indicated that the environment was incorporated well in the planning procedure based on the concepts, and could also demonstrate the effects of planning measures on environment spatially, explicitly, and in real-time, facilitating the participation of planning practitioners and decision-making. Some proposals of how to promote STEEP application in China were suggested.


CRISPR-C: circularization of genes and chromosome by CRISPR in human cells.
Extrachromosomal circular DNA (eccDNA) and ring chromosomes are genetic alterations found in humans with genetic disorders. However, there is a lack of genetic engineering tools to recapitulate and study the biogenesis of eccDNAs. Here, we created a dual-fluorescence biosensor cassette, which upon the delivery of pairs of CRISPR/Cas9 guide RNAs, CRISPR-C, allows us to study the biogenesis of a specific fluorophore expressing eccDNA in human cells. We show that CRISPR-C can generate functional eccDNA, using the novel eccDNA biosensor system. We further reveal that CRISPR-C also can generate eccDNAs from intergenic and genic loci in human embryonic kidney 293T cells and human mammary fibroblasts. EccDNAs mainly forms by end-joining mediated DNA-repair and we show that CRISPR-C is able to generate endogenous eccDNAs in sizes from a few hundred base pairs and ranging up to 207 kb. Even a 47.4 megabase-sized ring chromosome 18 can be created by CRISPR-C. Our study creates a new territory for CRISPR gene editing and highlights CRISPR-C as a useful tool for studying the cellular impact, persistence and function of eccDNAs.


Imaging findings of splenic hamartoma.
To assess CT and MR manifestations and their diagnostic value in splenic hamartoma with review of literatures. We described a woman who was accidentally found to have a splenic tumor by ultrasound of the abdomen. CT and MR findings of this splenic hamartoma were proved by pathology retrospectively. The CT and MR findings in this case included a ball-like mass with homogeneous mild-hypodensity lesions on non-enhanced CT scans or isointensity on T1-weighted images and mild hypointensity on T2-weighted images, progressive homogeneous enhancement on multiple-phase spiral CT and MR enhanced scans, and isodense enhancement on delayed post-contrast CT scans and obvious hyperintensity relative to the spleen on delayed MR images. Splenic hamartoma has some specific radiological features. However, the diagnosis of this disease must be based on clinical features and confirmed by pathology.


Heritabilities, social environment effects and genetic correlations of social behaviours in a cooperatively breeding vertebrate.
Social animals interact frequently with conspecifics, and their behaviour is influenced by social context, environmental cues and the behaviours of interaction partners, allowing for adaptive, flexible adjustments to social encounters. This flexibility can be limited by part of the behavioural variation being genetically determined. Furthermore, behaviours can be genetically correlated, potentially constraining independent evolution. Understanding social behaviour thus requires carefully disentangling genetic, environmental, maternal and social sources of variations as well as the correlation structure between behaviours. Here, we assessed heritability, maternal, common environment and social effects of eight social behaviours in Neolamprologus pulcher, a cooperatively breeding cichlid. We bred wild-caught fish in a paternal half-sibling design and scored ability to defend a resource against conspecifics, to integrate into a group and the propensity to help defending the group territory ("helping behaviour"). We assessed genetic, social and phenotypic correlations within clusters of behaviours predicted to be functionally related, namely "competition," "aggression," "aggression-sociability," "integration" and "integration-help." Helping behaviour and two affiliative behaviours were heritable, whereas there was little evidence for a genetic basis in all other traits. Phenotypic social effects explained part of the variation in a sociable and a submissive behaviour, but there were no maternal or common environment effects. Genetic and phenotypic correlation within clusters was mostly positive. A group's social environment influenced covariances of social behaviours. Genetic correlations were similar in magnitude but usually exceeding the phenotypic ones, indicating that conclusions about the evolution of social behaviours in this species could be provisionally drawn from phenotypic data in cases where data for genetic analyses are unobtainable.


Prolactin and growth hormone responses to hypoglycemia in patients with rheumatoid arthritis and ankylosing spondylitis.
Prolactin (PRL) and growth hormone (GH) are pituitary hormones with immunomodulating properties. Their upregulated secretion may play a role in the pathogenesis of chronic inflammatory diseases. We evaluated PRL and GH responses to secretion stimulus in patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Insulin hypoglycemia (0.1 IU/kg) was induced in 15 women with RA, 18 men with AS, and healthy controls matched for age, sex and body mass index. Plasma concentrations of glucose, PRL, GH, interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-a) were analyzed. RA patients had significantly lower area under the curve (AUC) of PRL (p = 0.049) compared to RA controls. During hypoglycemia double or higher increase of plasma PRL occurred in 5 RA (33%) patients and in 8 RA controls (57%). Using the General Linear Model procedure, no significant differences in PRL or GH responses were observed in patients with RA and AS. TNF-a was higher in patients with RA compared to RA controls (p < 0.05). There was no significant difference in TNF-a concentrations between AS patients and AS controls. IL-6 was higher in RA patients compared to controls (p < 0.05) and in AS patients compared to controls (p < 0.01). Significant positive correlation was found between TNF-a levels and AUC of PRL in AS patients (r = 0.46, p = 0.047), but not in the 2 control groups or in RA patients. Our results indicate no upregulated PRL or GH responses to stimulation in premenopausal women with RA or men with AS.


Gastric digestion of raw and roasted almonds in vivo.
Almonds are an important dietary source of lipids, protein, and α-tocopherol. It has been demonstrated that the physical form of almond kernels influences their digestion and absorption, but the role of thermal processes on the digestion of almonds has received little attention. The objectives of this study were to examine the gastric emptying and nutrient composition of gastric chyme from pigs (used as a model for the adult human) fed a single meal of either raw or roasted almonds over a 12-h postprandial period (72 pigs total, 6 pigs at each diet-time combination). Concentrations of glucose, triacylglycerols, and α-tocopherol in peripheral plasma during the 12-h postprandial period were determined. For dry matter and lipid, the gastric emptying profile was not different between raw and roasted almonds. Roasting almonds also did not influence gastric pH, or plasma glucose or triacylglycerols levels. In contrast, the gastric emptying of protein was more rapid for raw almonds compared to roasted almonds (P < 0.01) and intragastric protein content exhibited segregation (P < 0.001) throughout the stomach, with raw almonds having a higher level of segregation compared to roasted almonds. Postprandial plasma α-tocopherol levels were, on average 33% greater (P < 0.001) after consumption of raw almonds, most likely as a result of the higher concentration of α-tocopherol in raw almonds compared to roasted almonds. Roasting of almonds did not influence the overall gastric emptying process, but did lead to differences in the distribution of protein in the stomach and to the gastric emptying of protein.


The structure-directing amine changes everything: structures and optical properties of two-dimensional thiostannates.
Two different two-dimensional thiostannates (SnS) were synthesized using tris(2-aminoethyl)amine (tren) or 1-(2-aminoethyl)piperidine (1AEP) as structure-directing agents. Both structures consist of negatively charged thiostannate layers with charge stabilizing cations sandwiched in-between. The fundamental building units are Sn3S4 broken-cube clusters connected by double sulfur bridges to form polymeric (Sn3S72-)n honeycomb hexagonal layers. The compounds are members of the R-SnS-1 family of structures, where R indicates the type of cation. Despite consisting of identical structural units, the band gaps of the two semiconducting compounds were found to differ substantially at 2.96 eV (violet-blue light) and 3.21 eV (UV light) for tren-SnS-1 and 1AEP-SnS-1, respectively. Aiming to explain the observed differences in optical properties, the structures of the two thiostannates were investigated in detail based on combined X-ray diffraction, solid-state 13C and 119Sn MAS NMR spectroscopy and scanning electron microscopy studies. The compound tren-SnS-1 has a hexagonal structure consisting of planar SnS layers with regular hexagonal pores and disordered cations, whereas 1AEP-SnS-1 has an orthorhombic unit cell with ordered cations, distorted hexagonal pores and non-planar SnS layers. In the formation of 1AEP-SnS-1, an intramolecular reaction of the structure-directing piperidine takes place to form an N-heterobicyclic cation through in situ C-H activation. Hirshfeld surface analysis was used to investigate the interaction between the SnS layers and cations in 1AEP-SnS-1 and revealed that the most nucleophilic part of the SnS sheets is one of the two crystallographically distinct double sulfur bridges.


Fibrinogen synthesis in the isolated perfused rat liver: stimulation by a humoral factor associated with trauma.
Fibrinogen synthesis was measured by the [14C]carbonate method in isolated rat livers perfused with blood from normal rats and rats injected with turpentine 1, 5, and 16 hr before bleeding. Five- and 16-hr blood increased synthesis 2-fold, compared with normal and 1-hr blood. Turpentine injection caused a 10-fold rise in fibrinogen fragment D immunoreactivity (measured by serum radioimmunoassay) 5 and 16 hr after injection, compared with normal rats, and rats bled 1 hr after turpentine injection. Isolation of fibrinogen-related antigen by immunoaffinity chromatography, followed by polyacrylamide gel electrophoresis, revealed substantial increases in fibrinogen-related protein in 5- and 16-hr blood. The largest relative increase was in protein with electrophoretic mobility similar to that of fragment D1. These studies demonstrate the presence of a transferable blood factor which, produced in response to injury, stimulates fibrinogen synthesis by the liver. They lend support to the possibility that this factor may be fragment D1 or one or more other derivatives of the D domain of the fibrinogen molecule.


Can estrogens promote hypertension during systemic lupus erythematosus?
SLE is a chronic autoimmune inflammatory disorder that predominantly affects young women. Based on this observation, it has been speculated that sex steroids, particularly estrogens, contribute to SLE disease progression. Young women with SLE are at an increased risk for the development of hypertension yet the reasons for this are unclear. One potential mechanism for the increased risk of hypertension during SLE is the chronic inflammation caused by immune complex mediated tissue injury. Estrogens are known to have an immunomodulatory role that can lead to the production of characteristic autoantibodies important for immune complex formation. Therefore, it is conceivable that during SLE estrogens contribute to tissue injury, increased inflammation and hypertension. This brief review discusses the increased risk for hypertension during SLE, the role of estrogens in immune system function, evidence for estrogens in SLE, and a possible link between estrogens and SLE hypertension.


Efficacy of Horizontal Alveolar Ridge Expansion Through the Alveolar Ridge Split Procedure: A Systematic Review and Meta-Analysis.
Alveolar ridge split (ARS) is ridge augmentation to mitigate ridge width loss that typically follows tooth extraction. This study aimed to determine the efficacy of ARS on alveolar ridge horizontal dimensional changes and the survival rates of implants placed into the same sites. An electronic and manual search was conducted for English articles published up to January 1, 2021. The PICO (problem, intervention, comparison, outcome) model for quantitative studies was established to address the following two focused questions: (1) What are the effects of the ARS technique on increasing alveolar width and implant survival?; and (2) what are the factors that influence the efficacy of the ARS technique? The outcome measures in this systematic review and meta-analysis were mean alveolar ridge gain-horizontal (buccolingual) in millimeters from baseline (initial presentation) to final assessment (minimum of 12 weeks after ARS), implant survival rate, and patient-reported complication rate. The risk of bias was evaluated using the ROBINS-I assessment tool for non-randomized interventional studies. Weighted means were calculated, and pooled effects and 95% confidence intervals (95% CI) were depicted on forest plots. Publication bias was assessed by funnel plot and Rosenthal Statistics. A sensitivity analysis was undertaken to assess the primary outcome. Overall, 35 studies met the inclusion criteria and were included in the systematic review. The mean alveolar ridge gain for ARS was 3.06 mm (95% CI: 3.01 to 3.12 mm). A mean gain of 2.99 mm (95% CI: 2.93 to 3.04 mm) was found after sensitivity analysis, excluding one article with a high risk of bias. There were no significant differences in ridge width in the group with bone graft (mean difference [95% CI] of 2.97 mm [2.91 to 3.03 mm]) and in the group without bone graft (mean difference [95% CI] of 3.06 mm [2.92 to 3.20 mm]). The ARS technique demonstrated a 98.17% implant survival rate in 4,446 implants, 4,103 of which were placed at the time of ARS with a 97.72% implant survival rate, and 343 placed in a delayed approach with a 99.14% implant survival rate. The risk of bias was low in 14.2%, low to moderate in 68.5%, moderate in 11.4%, and severe/moderate in 5.7% of the included studies. ARS shows a high implant survival rate in narrow alveolar ridges, adequate horizontal alveolar ridge dimensional gain regardless of adding grafting material, and minimal patient-reported complications.


[Survival of helminth eggs in the wastewater mud in the sludge beds of Chita waterworks].
The species composition, size, and survival of human and domestic animal helminth eggs was determined in the wastewater mud in the sludge beds of the waterworks of Chita. It was shown that when the wastewater mud was little dried in the sludge beds under distinctly continental climatic conditions for three years, their complete disinvasion did not take place. The eggs of seat-worms (Enterobius vermicularis), whipworms (Trichuris trichiura), broad tapeworms (Diphylobotrium latum), and teniae were undetectable in the mud samples after the second and third year of drying. Surviving Ascaris eggs may develop in the soil to the invasion stage under the climatic conditions of Chita, by creating a risk for new infections.


Decline in climate resilience of European wheat.
Food security relies on the resilience of staple food crops to climatic variability and extremes, but the climate resilience of European wheat is unknown. A diversity of responses to disturbance is considered a key determinant of resilience. The capacity of a sole crop genotype to perform well under climatic variability is limited; therefore, a set of cultivars with diverse responses to weather conditions critical to crop yield is required. Here, we show a decline in the response diversity of wheat in farmers' fields in most European countries after 2002-2009 based on 101,000 cultivar yield observations. Similar responses to weather were identified in cultivar trials among central European countries and southern European countries. A response diversity hotspot appeared in the trials in Slovakia, while response diversity "deserts" were identified in Czechia and Germany and for durum wheat in southern Europe. Positive responses to abundant precipitation were lacking. This assessment suggests that current breeding programs and cultivar selection practices do not sufficiently prepare for climatic uncertainty and variability. Consequently, the demand for climate resilience of staple food crops such as wheat must be better articulated. Assessments and communication of response diversity enable collective learning across supply chains. Increased awareness could foster governance of resilience through research and breeding programs, incentives, and regulation.


Technology, attributions, and emotions in post-secondary education: An application of Weiner's attribution theory to academic computing problems.
As technology becomes increasingly integrated with education, research on the relationships between students' computing-related emotions and motivation following technological difficulties is critical to improving learning experiences. Following from Weiner's (2010) attribution theory of achievement motivation, the present research examined relationships between causal attributions and emotions concerning academic computing difficulties in two studies. Study samples consisted of North American university students enrolled in both traditional and online universities (total N = 559) who responded to either hypothetical scenarios or experimental manipulations involving technological challenges experienced in academic settings. Findings from Study 1 showed stable and external attributions to be emotionally maladaptive (more helplessness, boredom, guilt), particularly in response to unexpected computing problems. Additionally, Study 2 found stable attributions for unexpected problems to predict more anxiety for traditional students, with both external and personally controllable attributions for minor problems proving emotionally beneficial for students in online degree programs (more hope, less anxiety). Overall, hypothesized negative effects of stable attributions were observed across both studies, with mixed results for personally controllable attributions and unanticipated emotional benefits of external attributions for academic computing problems warranting further study.


Assessing Health Care Use Trajectories After the Onset of Functional Disability: Application of a Group-Based Trajectory Model.
While older adults with activity limitations have high levels of health care use, we do not know how this varies over time. We aimed to assess trajectories of Emergency Department (ED) use and hospitalization after the onset of receipt of help with self-care or mobility. We used the 2011-2017 National Health Aging Trends Study (NHATS) linked to Medicare claims to identify a cohort of older adults who began to receive help with self-care or mobility in the past year. Primary outcome was the quarterly rates of ED use and/or hospitalization over the 24 months following the onset of receiving help. We fit a Group-Based Trajectory Model to identify the trajectories of ED use or hospitalization and assessed the association of characteristics preceding and concurrent to the onset of help with trajectory group membership. Among 1,687 NHATS respondents newly receiving help with self-care/mobility, health care use escalated and then immediately fell. We found distinct trajectories of ED use and hospitalization: delayed rise (13.5%), falling (26.2%), and persistent (60.4%). Trajectory group membership was predicted by clinical, economic, and regional characteristics; and the individuals in each group differed in terms of concurrent new illnesses and degree of disability. While activity limitations are a strong predictor of health care use among older adults, trajectories of health care use are heterogeneous. Along with clinical characteristics, potentially modifiable household and regional factors shaped health care trajectories, indicating that addressing these factors could potentially shift health care use patterns.


A methodological approach to identify cheap and accurate indicators for biodiversity assessment: application to grazing management and two grassland bird species.
In response to environmental threats, numerous indicators have been developed to assess the impact of livestock farming systems on the environment. Some of them, notably those based on management practices have been reported to have low accuracy. This paper reports the results of a study aimed at assessing whether accuracy can be increased at a reasonable cost by mixing individual indicators into models. We focused on proxy indicators representing an alternative to the direct impact measurement on two grassland bird species, the lapwing Vanellus vanellus and the redshank Tringa totanus. Models were developed using stepwise selection procedures or Bayesian model averaging (BMA). Sensitivity, specificity, and probability of correctly ranking fields (area under the curve, AUC) were estimated for each individual indicator or model from observational data measured on 252 grazed plots during 2 years. The cost of implementation of each model was computed as a function of the number and types of input variables. Among all management indicators, 50% had an AUC lower than or equal to 0.50 and thus were not better than a random decision. Independently of the statistical procedure, models combining management indicators were always more accurate than individual indicators for lapwings only. In redshanks, models based either on BMA or some selection procedures were non-informative. Higher accuracy could be reached, for both species, with model mixing management and habitat indicators. However, this increase in accuracy was also associated with an increase in model cost. Models derived by BMA were more expensive and slightly less accurate than those derived with selection procedures. Analysing trade-offs between accuracy and cost of indicators opens promising application perspectives as time consuming and expensive indicators are likely to be of low practical utility.


Pressure-induced phase transition in thiol-capped CdTe nanoparticles.
Phase transitions for CdTe nanoparticles (NPs) under high pressure up to 37.0 GPa have been studied using fluorescence measurements. The phase transition from cinnarbar to rocksalt phase has been observed in CdTe NPs solution at 5.8 GPa, which is much higher than the phase transition pressure of bulk CdTe (3.8 GPa) and that of CdTe NPs in solid form (0.8 GPa). CdTe NPs solution therefore shows elevated phase transition pressure and enhanced stability against pressure compared with bulk CdTe and CdTe NPs in solid forms. The enhanced stability of CdTe NPs solution has been attributed to possible shape change in the phase transition and/or inhomogeneous strains in nanoparticle solutions.


Holocentric chromosomes of Luzula elegans are characterized by a longitudinal centromere groove, chromosome bending, and a terminal nucleolus organizer region.
The structure of holocentric chromosomes was analyzed in mitotic cells of Luzula elegans. Light and scanning electron microscopy observations provided evidence for the existence of a longitudinal groove along each sister chromatid. The centromere-specific histone H3 variant, CENH3, colocalized with this groove and with microtubule attachment sites. The terminal chromosomal regions were CENH3-negative. During metaphase to anaphase transition, L. elegans chromosomes typically curved to a sickle-like shape, a process that is likely to be influenced by the pulling forces of microtubules along the holocentric axis towards the corresponding microtubule organizing regions. A single pair of 45S rDNA sites, situated distal to Arabidopsis-telomere repeats, was observed at the terminal region of one chromosome pair. We suggest that the 45S rDNA position in distal centromere-free regions could be required to ensure chromosome stability.


Hypercoagulability in multiple myeloma and its precursor state, monoclonal gammopathy of undetermined significance.
Patients with multiple myeloma are at an increased risk of venous thromboembolism (VTE), especially when treated with the immunomodulatory drugs, thalidomide and lenalidomide, in combination with dexamethasone and/or chemotherapy. Several studies have shown that patients with multiple myeloma precursor disease (monoclonal gammopathy of undetermined significance [MGUS]) also have a higher risk of thrombosis compared to the general population. The underlying mechanisms for the hypercoagulable state are not completely understood. In this review, we discuss risk factors for thrombosis in multiple myeloma, as well as prophylactic strategies, the evidence for thrombosis among patients with MGUS, and proposed mechanisms for the hypercoagulability.


Breakout-lateral root emergence in Arabidopsis thaliana.
Lateral roots are determinants of plant root system architecture. Besides providing anchorage, they are a plant's means to explore the soil environment for water and nutrients. Lateral roots form post-embryonically and initiate deep within the root. On its way to the surface, the newly formed organ needs to grow through three overlying cell layers; the endodermis, cortex and epidermis. A picture is emerging that a tight integration of chemical and mechanical signalling between the lateral root and the surrounding tissue is essential for proper organogenesis. Here we review the latest progress made towards our understanding of the fascinating biology underlying lateral root emergence in Arabidopsis.


Dissociable effects of averted "gaze" on the priming of bodily representations and motor actions.
Gaze direction is an important stimulus that signals key details about social (dis)engagement and objects in our physical environment. Here, we explore how gaze direction influences the perceiver's processing of bodily information. Specifically, we examined how averted versus direct gaze modifies the operation of effector-centered representations (i.e., specific fingers) versus movement-centered representations (i.e., finger actions). Study 1 used a stimulus-response compatibility paradigm that tested the priming of a relevant effector or relevant movement, after observing videos of direct or averted gaze. We found a selective priming of relevant effectors, but only after averted gaze videos. Study 2 found similar priming effects with symbolic direction cues (averted arrows). Study 3 found that averted gaze cues do not influence generic spatial compatibility effects, and thus, are specific to body representations. In sum, this research suggests that both human and symbolic averted cues selectively prime relevant body-part representations, highlighting the dynamic interplay between our bodies, minds, and environments.


A paired-end sequencing strategy to map the complex landscape of transcription initiation.
Recent studies using high-throughput sequencing protocols have uncovered the complexity of mammalian transcription by RNA polymerase II, helping to define several initiation patterns in which transcription start sites (TSSs) cluster in both narrow and broad genomic windows. Here we describe a paired-end sequencing strategy, which enables more robust mapping and characterization of capped transcripts. We used this strategy to explore the transcription initiation landscape in the Drosophila melanogaster embryo. Extending the previous findings in mammals, we found that fly promoters exhibited distinct initiation patterns, which were linked to specific promoter sequence motifs. Furthermore, we identified many 5' capped transcripts originating from coding exons; our analyses support that they are unlikely the result of alternative TSSs, but rather the product of post-transcriptional modifications. We demonstrated paired-end TSS analysis to be a powerful method to uncover the transcriptional complexity of eukaryotic genomes.


Optic disc haemorrhages at baseline as a risk factor for poor outcome in the Idiopathic Intracranial Hypertension Treatment Trial.
The risk of optic disc haemorrhages on visual outcome in idiopathic intracranial hypertension (IIH) is unknown. We report the type and frequency of optic disc haemorrhages and other funduscopic abnormalities at baseline in the study eye of the 133 subjects enrolled in the Idiopathic Intracranial Hypertension Treatment Trial completing 6 months of follow-up. We reviewed optic disc photographs to tabulate the frequency and type of optic disc haemorrhages, other funduscopic abnormalities and papilloedema grades of the study eye at baseline and analyse if their presence is associated with a poor visual outcome. 27.2% of subjects had nerve fibre layer haemorrhages in at least one eye. Five of seven, 71% of subjects that met criteria for treatment failure, had nerve fibre layer haemorrhages in at least one eye (Fisher's exact test: p=0.02). There was a good correlation between presence of nerve fibre layer haemorrhages and Frisén grade (Spearman's correlation, p=0.002; r=0.271). Subjects with nerve fibre layer haemorrhages had a higher cerebrospinal fluid pressure (40.0 mm water, p=0.04). There was poor correlation between nerve fibre layer haemorrhages at baseline and the perimetric mean deviation change at 6 months. Cotton wool spots were present in 4% of subjects, exudates in 3% and pseudodrusen in 4%. Nerve fibre layer haemorrhages are common in patients with IIH with mild visual loss and correlate with the severity of the papilloedema. They occur more frequently in treatment failure subjects and therefore may be associated with poor visual outcomes. NCT01003639, Post-results.


Preoperative infrarenal abdominal aorta balloon catheter occlusion combined with Bakri tamponade reduced maternal morbidity of placenta increta/percreta.
Placenta increta/percreta is an increasingly common and life-threatening obstetric complication. It poses a management challenge to clinicians. The present study aimed to evaluate efficacy and safety of preoperative placement of infrarenal abdominal aorta balloon catheter (IAABC) alone or combined with Bakri tamponade for the management of cases with placenta increta/percreta. We retrospectively analyzed all cases with placenta increta/percreta at a tertiary referral teaching hospital in China between the year 2014 and 2017. Statistical analysis considered the individual subgroups: IAABC placed group and control group (without IAABC), and compared their maternal-fetal outcomes. The study covered 86 cases with placenta increta. For cases in the IAABC placed group (n = 48), significant reductions were noted in maternal morbidity including estimated blood loss (EBL), EBL ≥ 2000 mL, blood products transfusions, postpartum hemorrhage, operative time, intensive care unit admission, and postoperative days (P < .05 for all). The overall rate of hysterectomy was much lower (4.2%vs 23.7%, P = .018), compared with those in the control group (n = 38). Furthermore, in the IAABC placed group, hysterectomy was avoided in a further 17 cases combined with Bakri tamponade. In the control group, 10 cases were successful in preserving uterus by Bakri tamponade. Four cases failed and needed reoperation (3 uterine arterial embolism, 1 hysterectomy). There were no differences in fetal outcomes between the 2 groups. Eighteen cases were diagnosed with placenta percreta. Almost all the cases (17/18) inevitably underwent caesarean hysterectomy. Only 1 case was treated with a combination of IAABC and Bakri tamponade, and successfully reserved uterus. No differences were observed in any other outcomes, except for a significant less mean operative time (P = .017) in cases with IAABC placed (n = 10), compared with those without IAABC (n = 8). Only 1 case had a femoral artery thrombosis directly related to IAABC placement and recovered after conservative treatment. There was no maternal or neonatal death in this study. Prophylactic insertion of IAABC alone or combined with Bakri tamponade should be safe and effective in controlling intraoperative bleeding due to placenta increta, thus hysterectomy could be avoided. It seems to be less beneficial to women with placenta percreta. Bakri tamponade can be a good choice in the management of placenta increta/percreta before more aggressive surgeries.


Antimicrobial activity of essential oils and chloroform alone and combinated with cetrimide against Enterococcus faecalis biofilm.
The Enterococcus faecalis bacteria have been identified as the most commonly recovered species from teeth with persistent endodontic infections. The antimicrobial activity of essential oils and chloroform (CHL), alone and in association with various concentrations of cetrimide (CTR), against biofilm of Enterococcus faecalis was investigated. Solutions of CHL, eucalyptus oil (EO) and orange oil (OO) associated with CTR at 0.3%, 0.2%, 0.1%, and 0.05% were used to determine antimicrobial activity by exposing treated bovine dentine blocks to E. faecalis. Biofilms grown in the dentine blocks for 7 days were exposed to solutions for 2 and 5 min. Biofilm reduction between OO and EO at 2 min did not show any significant differences; however, OO had a higher kill percentage of biofilms than did the eucalyptus oil at 5 min (p < 0.01). Combinations with CTR at all concentrations achieved a 100% kill rate at 2 and 5 min. The association of CTR with solvent agents achieved the maximum antimicrobial activity against E. faecalis biofilms in dentine.


Influence of environment on testing of hydraulic sealers.
In vitro material testing is undertaken by conducting a series of tests following procedures outlined in international standards. All material properties are measured in water; however biological behavior is undertaken in alternative media such as Dulbecco's modified eagle medium (DMEM) or simulated body fluid. The aim of this study was to characterize four dental root canal sealers and study their properties in different media. Four dental root canal sealers were assessed. They were characterized by a combination of techniques and the sealer properties were tested as specified by ISO 6876 (2012) and also in alternative media. The sealer biocompatibility was measured by cell function and proliferation assays of elutions. All sealers complied with ISO specifications. The material properties were effected by the type of soaking medium used and the surface micromorphology and elemental composition were dependent on the soaking solution type. Both BioRoot and MTA Fillapex showed cytotoxicity which reduced at higher dilutions. The material chemistry, presentation, environmental conditions and testing methodology used affected the sealer properties. Standards specific to sealer type are thus indicated. Furthermore the methodology used in the standard testing should be more relevant to clinical situations.


Shenxiang Suhe pill improves cardiac function through modulating gut microbiota and serum metabolites in rats after acute myocardial infarction.
Shenxiang Suhe pill (SXSH), a traditional Chinese medicine, is clinically effective against coronary heart disease, but the mechanism of cardiac-protective function is unclear. We investigated the cardiac-protective mechanism of SXSH via modulating gut microbiota and metabolite profiles. Sprague-Dawley (SD) male rats were randomly divided into 6 groups (n = 8): Sham, Model, SXSH (Low, 0.063 g/kg; Medium, 0.126 g/kg; High, 0.252 g/kg), and Ato (atorvastatin, 20 mg/kg). Besides the Sham group, rats were modelled with acute myocardial infarction (AMI) by ligating the anterior descending branch of the left coronary artery (LAD). After 3, 7, 14 days' administration, ultrasound, H&E staining, serum enzymic assay, 16S rRNA sequencing were conducted to investigate the SXSH efficacy. Afterwards, five groups of rats: Sham, Model, Model-ABX (AMI with antibiotics-feeding), SXSH (0.126 g/kg), SXSH-ABX were administrated for 14 days to evaluate the gut microbiota-dependent SXSH efficacy, and serum untargeted metabolomics test was performed. 0.126 g/kg of SXSH intervention for 14 days increased ejection fraction (EF, 78.22%), fractional shortening (FS, 109.07%), and aortic valve flow velocities (AV, 21.62%), reduced lesion area, and decreased serum LDH (8.49%) and CK-MB (10.79%). Meanwhile, SXSH upregulated the abundance of Muribaculaceae (199.71%), Allobaculum (1744.09%), and downregulated Lactobacillus (65.51%). The cardiac-protective effect of SXSH was disrupted by antibiotics administration. SXSH altered serum metabolites levels, such as downregulation of 2-n-tetrahydrothiophenecarboxylic acid (THTC, 1.73%), and lysophosphatidylcholine (lysoPC, 4.61%). The cardiac-protective effect and suggested mechanism of SXSH could provide a theoretical basis for expanding its application in clinic.


Complex mechanisms regulate developmental expression of the matA (HMG) mating type gene in homothallic Aspergillus nidulans.
Sexual reproduction is a fundamental developmental process that allows for genetic diversity through the control of zygote formation, recombination, and gametogenesis. The correct regulation of these events is paramount. Sexual reproduction in filamentous fungi, including mating strategy (self-fertilization/homothallism or outcrossing/heterothallism), is determined by the expression of mating type genes at mat loci. Aspergillus nidulans matA encodes a critical regulator that is a fungal ortholog of the hSRY/SOX9 HMG box proteins. In contrast to well-studied outcrossing systems, the molecular basis of homothallism and role of mating type genes during a self-fertile sexual cycle remain largely unknown. In this study the genetic model organism, A. nidulans, has been used to investigate the regulation and molecular functions of the matA mating type gene in a homothallic system. Our data demonstrate that complex regulatory mechanisms underlie functional matA expression during self-fertilization and sexual reproduction in A. nidulans. matA expression is suppressed in vegetative hyphae and is progressively derepressed during the sexual cycle. Elevated levels of matA transcript are required for differentiation of fruiting bodies, karyogamy, meiosis, and efficient formation of meiotic progeny. matA expression is driven from both initiator (Inr) and novel promoter elements that are tightly developmentally regulated by position-dependent and position-independent mechanisms. Deletion of an upstream silencing element, matA SE, results in derepressed expression from wild-type (wt) promoter elements and activation of an additional promoter. These studies provide novel insights into the molecular basis of homothallism in fungi and genetic regulation of sexual reproduction in eukaryotes.


Urinary excretion of thyroid hormone in CKD patients: a proof-of-concept of nephrogenic hypothyroidism.
Patients with chronic kidney disease (CKD) complicated by hypothyroidism exhibit a higher prevalence of urine protein than that in the general population. This study was aimed at investigating thyroid hormones and thyroid hormone-binding proteins excreted in urine to elucidate the urine protein-associated underlying mechanisms of hypothyroidism. Between November 2016 and August 2018, thyroid function (serum free T3 [sFT3], free T4 [sFT4], and thyroid-stimulating hormone [sTSH]), kidney function (estimated glomerular filtration rate [eGFR]), thyroid antibodies and albumin (Alb) were evaluated in 99 Japanese CKD patients with proteinuria at our outpatient clinic. A urine examination was also performed to assess the following parameters: total T3, total T4, TSH, Alb, preAlb, thyroid-binding globulin, and protein. The median patient age at study recruitment was 60 years; 50 patients (50.5%) were male. The median eGFR and Alb level were 20.3 ml/min/1.73 m2 and 3.8 g/dL, respectively. 21 patients (21.2%) were diagnosed with nephrotic syndrome (NS). The median sFT3, sFT4, and sTSH levels were within normal limits. Approximately 70% of the patients had thyroid dysfunction and 51.5% had overt or subclinical hypothyroidism without predominantly antibody positive. Regarding NS and non-NS patients, age and Alb were significantly different between these groups, while sex and eGFR were not significant, but the urinary T4 and TSH levels were higher in the NS group; thus, more severe hypothyroid. We found a significant association between hypothyroidism and NS regardless of sex and antibodies. Urinary loss of thyroid hormones must be a factor influencing hypothyroidism independent of autoimmunity.


[Desensitization of alpha-adrenoreceptors of the small intestine of the rat].
A study performed on the isolated section of the rat small intestine has shown that at a slow increase in the concentration of the specific alpha-adrenomimetic phenylephrine in the incubation medium 1.0 X 10(-8) M/sec) adrenoreceptors pass into a state of desensitization without excitation, and no reaction takes place. At 2.5 X 10(-8)-10 X 10(-8) M/sec the reaction develops depending on the rate of phenylephrine introduction and is stabilized at 5.5-5.8 X 10(-6) M. Apparently, under these conditions an equilibrium is set up between activation and desensitization of adrenoreceptors. The role of desensitization of alpha-adrenoreceptors in the regulation of adrenergic reaction is discussed.


The murine goblet cell protein mCLCA3 is a zinc-dependent metalloprotease with autoproteolytic activity.
Several members of the CLCA family of proteins, originally named chloride channels, calcium-activated, have been shown to modulate chloride conductance in various cell types via an unknown mechanism. Moreover, the human (h) hCLCA1 is thought to modulate the severity of disease in asthma and cystic fibrosis (CF) patients. All CLCA proteins are post-translationally cleaved into two subunits, and recently, a conserved HEXXH zinc-binding amino acid motif has been identified, suggesting a role for CLCA proteins as metalloproteases. Here, we have characterized the cleavage and autoproteolytic activity of the murine model protein mCLCA3, which represents the murine orthologue of human hCLCA1. Using crude membrane fractions from transfected HEK293 cells, we demonstrate that mCLCA3 cleavage is zinc-dependent and exclusively inhibited by cation-chelating metalloprotease inhibitors. Cellular transport and secretion were not affected in response to a cleavage defect that was introduced by the insertion of an E157Q mutation within the HEXXH motif of mCLCA3. Interspecies conservation of these key results was further confirmed with the porcine (p) orthologue of hCLCA1 and mCLCA3, pCLCA1. Importantly, the mCLCA3E157Q mutant was cleaved after co-transfection with the wild-type mCLCA3 in HEK293 cells, suggesting that an intermolecular autoproteolytic event takes place. Edman degradation and MALDI-TOF-MS of the protein fragments identified a single cleavage site in mCLCA3 between amino acids 695 and 696. The data strongly suggest that secreted CLCA proteins have zinc-dependent autoproteolytic activity and that they may cleave additional proteins.


Feasibility of an experiential community garden and nutrition programme for youth living in public housing.
Few published community garden studies have focused on low socio-economic youth living in public housing or used a community-based participatory research approach in conjunction with youth-focused community garden programmes. The objective of the present study was to evaluate the feasibility (i.e. demand, acceptability, implementation and limited-effectiveness testing) of a 10-week experiential theory-based gardening and nutrition education programme targeting youth living in public housing. In this mixed-methods feasibility study, demand and acceptability were measured using a combination of pre- and post-programme surveys and interviews. Implementation was measured via field notes and attendance. Limited-effectiveness was measured quantitatively using a pre-post design and repeated-measures ANOVA tests. Two public housing sites in the Dan River Region of south central Virginia, USA. Forty-three youth (primarily African American), twenty-five parents and two site leaders. The positive demand and acceptability findings indicate the high potential of the programme to be used and be suitable for the youth, parents and site leaders. Field notes revealed numerous implementation facilitators and barriers. Youth weekly attendance averaged 4·6 of 10 sessions. Significant improvements (P<0·05) were found for some (e.g. fruit and vegetable asking self-efficacy, overall gardening knowledge, knowledge of MyPlate recommendations), but not all limited-effectiveness measures (e.g. willingness to try fruits and vegetables, fruit and vegetable eating self-efficacy). This community-based participatory research study demonstrates numerous factors that supported and threatened the feasibility of a gardening and nutrition programme targeting youth in public housing. Lessons learned are being used to adapt and strengthen the programme for future efforts targeting fruit and vegetable behaviours.


Nanostructural characterization and catalytic analysis of hybridized platinum/phthalocyanine nanocomposites.
Organic crystals, such as phthalocyanine nanocrystal, were successfully hybridized with Pt nanoparticles using a nanohybridization technique. The presence of highly dispersed Pt nanoparticles on the surface of phthalocyanine was confirmed by the combination of transmission electron microscopy and three-dimensional electron tomography. Catalytic activities of hybridized samples with different degrees of dispersions were also examined as oxygen reduction reactivity (ORR) with a linear potential sweep method. It was found that oxygen reduction activity increased with increasing Pt dispersion, and reasonably high ORR was observed on Pt-dispersed phthalocyanine nanocrystal even at 2 wt% Pt loading.


MR cholangiopancreatography of bile and pancreatic duct abnormalities with emphasis on the single-shot fast spin-echo technique.
Magnetic resonance cholangiopancreatography (MRCP) is used for noninvasive work-up of patients with pancreaticobiliary disease. MRCP is comparable with invasive endoscopic retrograde cholangiopancreatography (ERCP) for diagnosis of extrahepatic bile duct abnormalities. In patients with choledocholithiasis, calculi appear as dark filling defects within the high-signal-intensity fluid at MRCP. Benign strictures due to sclerosing cholangitis are multifocal and alternate with slight dilatation or normal-caliber bile ducts, producing a beaded appearance. Dilatation of both the pancreatic and bile ducts at MRCP is highly suggestive of a pancreatic head malignancy. Side-branch ectasia is the most prominent and specific feature of chronic pancreatitis. MRCP is more sensitive than ERCP in detection of pancreatic pseudocysts because less than 50% of pseudocysts fill with contrast material. Because the mucin secreted by biliary cystadenomas and cystadenocarcinomas causes filling defects and partial obstruction of contrast material at ERCP, MRCP is potentially more accurate in demonstrating the extent of these tumors. In patients with biliary-enteric anastomoses, MRCP is the imaging modality of choice for the work-up of suspected pancreaticobiliary disease. A potential use of MRCP is the demonstration of aberrant bile duct anatomy before cholecystectomy. MRCP is also accurate in detection of pancreas divisum.


Hybrid augmented reality simulator: preliminary construct validation of laparoscopic smoothness in a urology residency program.
We examined the usefulness, reliability and applicability of the smoothness metric of the ProMIS hybrid simulator (Haptica, Dublin, Ireland) for a urology residency program. A total of 15 urology residents divided into junior and senior cohorts were followed prospectively for 6 training sessions. Validated McGill Inanimate System for Training and Evaluation of Laparoscopic Skills (MISTELS) laparoscopic tasks were used. The ProMIS hybrid simulator smoothness parameter, a unit-free metric of movement efficiency, was recorded using 3-dimensional visual tracking technology. Results were compared between cohorts at the midpoint and end of the defined training sessions. End of study junior means were also retrospectively compared to senior mid training means. Statistical significance was determined using the Mann-Whitney U test (alpha = 0.05). Statistically significant differences between 8 junior and 7 senior cohorts were measured in all MISTELS tasks. A statistically significant performance variation was also detected at the mid and end testing times. When juniors and seniors were compared between sessions 1 and 3, and 4 and 6, statistically significant performance improvements were noted. Lastly, statistical differences were also maintained when mid session senior means were compared to end of session junior means. A 38% improvement in task completion in the senior cohort as well as a 10-fold decrease in variance was observed compared to a 12% improvement in juniors, indicating greater efficiency of movement in seniors. The laparoscopic smoothness metric in the hybrid simulator demonstrated construct validity by effectively differentiating between experienced and novice urology residents using validated MISTELS tasks. The outcome suggests that the hybrid simulator smoothness metric is a valuable asset in residency programs for preparatory training for live operative experience, allowing improved trainee assessment.


Modeling the efficiency of phosphorus utilization in growing pigs.
Microbial phytase has been used to reduce P excretion from swine to mitigate environmental pollution. The objective of the study was to quantify the effect of feeding a low-P phytase-supplemented diet on growth and P utilization in growing pigs using mathematical models. A total of 20 weaned piglets (BW = 6.5 kg) housed in metabolism cages were randomly assigned to a standard diet (STD) or P-amended diet containing reduced P content and supplemented with phytase (AMN) with 10 pigs/diet. Body weight and feed consumption were recorded weekly so complete growth and cumulative P intake (cPI) curves could be modeled. A function with fixed point of inflexion (Gompertz) and a variable point of inflexion (generalized Michaelis-Menten) were considered in determining bioequivalence by analyzing BW vs. age relationships, whereas the monomolecular function was used to describe BW vs. cPI. All functions were incorporated into a nonlinear mixed effects model, and a first-order autoregressive correlation structure was implemented to take into account repeated measures. There was no difference between the 2 groups in final BW when the Gompertz equation was fitted (176 vs. 178 kg with SE of 7 kg for the STD and AMN, respectively) or the rate parameter (0.0140 vs. 0.0139 with SE of 0.0004 for the STD and AMN, respectively). The generalized Michaelis-Menten equation also showed a similar trend. When BW was expressed as a function of cPI the derivative with respect to cPI represented P efficiency, so it was possible to analyze the expected difference of the 2 diets in using P for BW gain and express it as a continuous function of cPI. The analysis showed through the entire growth period the difference in P efficiency was different from zero. On average, 56 g of supplemented inorganic P was consumed by a pig fed the AMN to reach market weight. In contrast, 309 g of supplemented inorganic P was consumed by the group fed the STD to reach similar BW. It would depend on other factors, but feeding pigs the AMN can result in economic benefit. Pigs fed the AMN excreted 19% less P compared with those fed the STD. In conclusion, nonlinear mixed model analysis (with repeated measures) was suitable for growth and efficiency analysis and showed that pigs fed the AMN consumed less than 20% of the inorganic P and performed as well as those fed the traditional inorganic P supplemented diet. The implications for mitigating P pollution, especially in areas where P loading is already problematic, are substantial.


[Cu81(PhS)46(tBuNH2)10(H)32]3+ Reveals the Coexistence of Large Planar Cores and Hemispherical Shells in High-Nuclearity Copper Nanoclusters.
Copper-based nanomaterials have attracted tremendous interest due to their unique properties in the fields of photoluminescence and catalysis. As a result, studies on the correlation between their molecular structure and their properties are of great importance. Copper nanoclusters are a new class of nanomaterials that can provide an atomic-level view of the crystal structure of copper nanoparticles. Herein, a high-nuclearity copper nanocluster with 81 copper atoms, formulated as [Cu81(PhS)46(tBuNH2)10(H)32]3+ (Cu81), was successfully synthesized and fully studied by X-ray crystallography, X-ray photoelectron spectroscopy, hydrogen evolution experiments, electrospray ionization mass spectrometry, nuclear magnetic resonance spectroscopy, and density functional theory calculations. Cu81 exhibits extraordinary structural characteristics, including (i) three types of novel epitaxial surface-protecting motifs; (ii) an unusual planar Cu17 core; (iii) a hemispherical shell, comprised of a curved surface layer and a planar surface layer; and (iv) two distinct, self-organized arrangements of protective ligands on the curved and planar surfaces. The present study sheds light on structurally unexplored copper nanomaterials and paves the way for the synthesis of high-nuclearity copper nanoclusters.


Oleanane-type triterpenoids of Aceriphyllum rossii and their diacylglycerol acyltransferase-inhibitory activity.
Six known triterpenoid compounds, 3-oxoolean-12-en-27-oic acid (1), gypsogenic acid (2), 3α-hydroxyolean-12-en-27-oic acid (3), 3β-hydroxyolean-12-en-27-oic acid (4), aceriphyllic acid A (5), and oleanolic acid (6), were isolated from the roots of Aceriphyllum rossii. Their chemical structures were determined by comparison with available (1)H-NMR and (13)C-NMR data on known compounds. All the isolated compounds were evaluated for inhibitory activity against human diacylglycerol acyltransferases 1 and 2. Most of the isolates exhibited a better inhibitory activity against diacylglycerol acyltransferase 2 (IC50: 11.6-44.2 µM) than against diacylglycerol acyltransferase 1 (IC50: 22.7-119.5 µM). In particular, compounds 1 and 5 showed strong inhibition efficacy towards diacylglycerol acyltransferases 1 and 2, and appeared to act competitively against oleoyl-CoA in vitro. The results also indicated that both compounds reduced newly synthesized triacylglycerol in HuTu80 and HepG2 cells. Oral administration of compound 1 significantly reduced postprandial triacylglycerol in mice following an oral lipid challenge. In conclusion, the current study indicates that compound 1 suppresses both de novo triacylglycerol biosynthesis and resynthesis through the inhibition of diacylglycerol acyltransferase activity, and therefore may be a useful agent for treating diseases associated with a high triacylglycerol level.


Serum immunoreactive prolyl hydroxylase in inflammatory rheumatic diseases.
Serum immunoreactive prolyl hydroxylase protein (S-IRPH) was measured in 56 patients with inflammatory rheumatic diseases, and the values were compared with those in 32 control subjects. S-IRPH was above the 95% confidence limit of the controls in about 70% of the patients with active systemic lupus erythematosus, rheumatoid arthritis, scleroderma, Reiter's syndrome, Sjögren's syndrome, polyarteritis nodosa, or polymyositis. Raised values were observed in about half of the patients with an erythrocyte sedimentation rate (ESR) of 21-50 and in about 90% of those with ESR of over 50, whereas only about 10% of the patients with an inactive disease had an S-IRPH concentration exceeding this limit. Only 1 out of 8 patients with active ankylosing spondylitis had a raised S-IRPH value. The results support previous data indicating that significant changes in collagen metabolism occur in active connective tissue diseases. Assays of S-IRPH might be of some value in assessing the activity of these diseases and in monitoring the treatment provided.


Health consequences of postsocialist transition: dietary and lifestyle determinants of plasma lipids in Yakutia.
The rapid social and cultural changes introduced by the collapse of the Soviet Union have resulted in important differences in cardiovascular health for indigenous Siberians. This study investigated diet and lifestyle determinants of plasma lipids in the Yakut, an indigenous Siberian herding population. The study used a cross-sectional design with data on 201 subjects in three urbanized towns and three rural communities in northeastern Siberia. Data on sociodemographic characteristics, dietary intake, and material lifestyle were collected, and lipids were analyzed from venous whole blood. Diet was analyzed using patterns of dietary intake based on principal components analysis of a dietary intake (food frequency) questionnaire. We identified three diet patterns: a traditional subsistence diet, a market foods diet, and a mixed diet. The effect of lifestyle on cardiovascular risk factors was measured using an ethnographically defined lifestyle index, with two orthogonal dimensions: subsistence lifestyle and modern lifestyle. Total cholesterol (TC) and low-density lipoprotein (LDL) were significantly higher among those consuming a traditional subsistence diet of meat and dairy products. A modern lifestyle was associated with lower TC and LDL but higher adiposity and higher risk of obesity. LDL and TC were higher in rural communities and lower in urbanized towns. The significantly higher lipid levels associated with a subsistence diet and indirectly with a subsistence lifestyle indicate the emergence of a significant health problem associated with the social and cultural changes occurring in Yakutia today. These findings underscore the need for dietary modification and promotion of physical activity among those most at risk for cardiovascular disease (CVD). Moreover, these results differ from those commonly seen in "modernizing" populations, in that elements of subsistence lifestyle are associated with an elevated rather than reduced risk of CVD. Such variable responses to lifestyle change emphasize the need to better understand the distinct social and historical events that may influence health changes among populations in transition.


Treatment Outcome of Carotid Artery Stenting Underwent within 14 Days of Stroke Onset - Consideration of Safety and Efficacy of Urgent Carotid Artery Stenting for Neurologically Progressing Patients.
As the safety and effectiveness of urgent carotid artery stenting (CAS) for neurologically progressing patients remain controversial, we retrospectively analyzed the outcome of urgent CAS based on the patients' pathophysiological condition and neuroimaging findings. We divided 71 patients who underwent CAS within 14 days of stroke onset into two groups. Group 1 (n = 35) was comprised of patients with progressing neurologic signs and a reversible ischemic penumbra on magnetic resonance images (MRI). They were treated by urgent CAS. Group 2 (n = 36) was neurologically stable and underwent prophylactic CAS. In all patients we recorded the National Institutes of Health Stroke Scale (NIHSS) score and the modified Rankin scale (mRS). Urgent CAS resulted in significant improvement in the NIHSS score, when compared before and after CAS in group 1 (5.3 ± 4.3, P < 0.01). The rate of good outcomes (mRS 0-2 at 3 months post-CAS) was 48.6% in group 1, and 75% in group 2. The cumulative incidence of ipsilateral stroke between 31 days and 1 year was 5.9% in group 1, and 0% in group 2. The procedural complication rate was similar in both groups (group 1: 5.7%, n = 2; group 2: 5.6%, n = 2). No patient suffered a symptomatic intracerebral hemorrhage. When the pathophysiological status and neuroimaging findings are used to determine patient eligibility for urgent CAS, this treatment improve neurologic outcome and can be performed as safely as prophylactic CAS in our cohort of patients with acute ischemic stroke.


Cardiopulmonary exercise testing predicts postoperative outcome in patients undergoing gastric bypass surgery.
For several types of non-cardiac surgery, the cardiopulmonary exercise testing (CPET)-derived variables anaerobic threshold (AT), peak oxygen consumption (VO2 peak), and ventilatory equivalent for CO(2) (VE/VCO2 ) are predictive of increased postoperative risk: less physically fit patients having a greater risk of adverse outcome. We investigated this relationship in patients undergoing gastric bypass surgery. All patients (<190 kg) who were referred for CPET and underwent elective gastric bypass surgery at the Whittington Hospital NHS Trust between September 1, 2009, and February 25, 2011, were included in the study (n=121). Fifteen patients did not complete CPET. CPET variables (VO2 peak, AT, and VE/VCO2 ) were derived for 106 patients. The primary outcome variables were day 5 morbidity and hospital length of stay (LOS). The independent t-test and Fisher's exact test were used to test for differences between surgical outcome groups. The predictive capacity of CPET markers was determined using receiver operating characteristic (ROC) curves. The AT was lower in patients with postoperative complications than in those without [9.9 (1.5) vs 11.1 (1.7) ml kg(-1) min(-1), P=0.049] and in patients with a LOS>3 days compared with LOS ≤ 3 days [10.4 (1.4) vs 11.3 (1.8) ml kg(-1) min(-1), P=0.023]. ROC curve analysis identified AT as a significant predictor of LOS>3 days (AUC 0.640, P=0.030). The VO2 peak and VE/VCO2 were not associated with postoperative outcome. AT, determined using CPET, predicts LOS after gastric bypass surgery.


Quantitative Clinical Staging for Patients With Malignant Pleural Mesothelioma.
Analysis of the International Association for the Study of Lung Cancer (IASLC) Malignant Pleural Mesothelioma (MPM) database revealed that clinical (cTNM) staging minimally stratified survival and was discrepant with pathological (pTNM) staging. To improve prognostic classification of MPM, alternative staging models based on quantitative parameters were explored. An institutional review board-approved MPM registry was queried to identify patients with available pathological and preoperative imaging data. Qualifying patients were randomly assigned to training and test sets in a 1:2 ratio. Computed cTNM and pTNM staging (AJCC Cancer Staging Manual, 7th ed.) were compared. Quantitative image analysis included tumor volume assessed from three-dimensional reconstruction of computed tomography scans (VolCT) and maximal fissural thickness (Fmax). Survival was estimated using the Kaplan-Meier method, and the relationship with VolCT was examined by Cox regression analysis to identify optimized cut-points. Performance of cTNM and quantitative models derived was compared in the test set using Harrell's C index. A total of 472 patients met inclusion criteria. TNM staging was concordant with pathological TNM staging in 171 of 472 (36.2%), understaged in 209 (44.2%), and overstaged in 92 (19.4%) patients. The most concordant feature was involvement of interlobar fissures. A quantitative clinical staging model comprising VolCT and Fmax (c-index = 0.638, 95% confidence interval [CI] = 0.603 to 0.673) performed statistically significantly better as a prognostic classifier when compared in the test set with cTNM (c-index = 0.562, 95% CI = 0.525 to 0.599, P = .001). Improved prognostic performance may be achievable by quantitative clinical staging combining VolCT and Fmax, providing a cost-effective and clinically relevant surrogate for clinical TNM stage.


Infectious mononucleosis in university students in the United kingdom: evaluation of the clinical features and consequences of the disease.
Infectious mononucleosis (IM) is common among university students. We undertook to analyze the clinical features and sequelae of the disease in a cohort of students at Edinburgh University. Consecutive IM case patients were recruited from 2000 through 2002 at the University Health Service after diagnosis of IM. IM resulted in marked reductions in student study time, physical exercise, and non-exercise-related social activities, and sustained increases in reported number of hours of sleep. The disease profile differed between the sexes, with significantly more females reporting fatigue, which was more likely to be prolonged (P = .003) and to lead to loss of study time (P = .013). Female case patients were more likely to discontinue their studies following IM (16% vs 0%; P = .056). Within the typically elevated lymphocyte counts in IM, we identified an elevated gammadelta T cell component that may contribute to the disease pathogenesis. IM results in substantial morbidity among university students, reported as more profound in females, and affecting academic studies, physical exercise, and social activities. Immunization to prevent IM and strategies to reduce post-IM disability would be beneficial in this population.


Incidence & prevalence of stroke in India: A systematic review.
There has been more than 100 per cent increase in incidence of stroke in low- and middle-income countries including India from 1970-1979 to 2000-2008. Lack of reliable reporting mechanisms, heterogeneity in methodology, study population, and small sample size in existing epidemiological studies, make an accurate estimation of stroke burden in India challenging. We conducted a systematic review of epidemiologic studies on stroke conducted in India to document the magnitude of stroke. All population-based, cross-sectional studies and cohort studies from India which reported the stroke incidence rate or cumulative stroke incidence and/or the prevalence of stroke in participants from any age group were included. Electronic databases (Ovid, PubMed, Medline, Embase and IndMED) were searched and studies published during 1960 to 2015 were included. A total of 3079 independent titles were identified for screening, of which 10 population-based cross-sectional studies were considered eligible for inclusion. Given the heterogeneity of the studies, meta-analysis was not carried out. The cumulative incidence of stroke ranged from 105 to 152/100,000 persons per year, and the crude prevalence of stroke ranged from 44.29 to 559/100,000 persons in different parts of the country during the past decade. These values were higher than those of high-income countries. A paucity of good-quality epidemiological studies on stroke in India emphasizes the need for a coordinated effort at both the State and national level to study the burden of stroke in India. Future investment in the population-based epidemiological studies on stroke would lead to better preventive measures against stroke and better rehabilitation measures for stroke-related disabilities in the country.


Acculturation, psychological adjustment, and parenting styles of Chinese immigrant mothers in the United States.
This study examined whether acculturation to American culture, maintenance of Chinese culture, and their interaction predicted Chinese immigrant parents' psychological adjustment and parenting styles. We hypothesized that American orientation would be associated with more positive psychological well-being and fewer depressive symptoms in immigrant mothers, which in turn would be associated with more authoritative parenting and less authoritarian parenting. The examination of the roles of Chinese orientation and the interaction of the 2 cultural orientations in relation to psychological adjustment and parenting were exploratory. Participants were 164 first-generation Chinese immigrant mothers in the United States (Mage = 37.80). Structural equation modeling was used to examine the direct and indirect effects of acculturation on psychological adjustment and parenting. Bootstrapping technique was used to explore the conditional indirect effects of acculturation on parenting as appropriate. American orientation was strongly associated with positive psychological well-being, which was in turn related to more authoritative parenting and less authoritarian parenting. Moreover, American and Chinese orientations interacted to predict depressive symptoms, which were in turn associated with more authoritarian parenting. Specifically, American orientation was negatively associated with depressive symptoms only at mean or high levels of Chinese orientation. Results suggest acculturation as a distal contextual factor and psychological adjustment as 1 critical mechanism that transmits effects of acculturation to parenting. Promoting immigrant parents' ability and comfort in the new culture independently or in conjunction with encouraging biculturalism through policy intervention efforts appear crucial for the positive adjustment of Chinese immigrant parents and children. (PsycINFO Database Record


Changing Molecular Markers of Antimalarial Drug Sensitivity across Uganda.
The potential spread of antimalarial drug resistance to Africa, in particular for artemisinins and key partner drugs, is a major concern. We surveyed Plasmodium falciparum genetic markers associated with drug sensitivity on 3 occasions at ∼6-month intervals in 2016 and 2017 at 10 sites representing a range of epidemiological settings in Uganda. For putative drug transporters, we found continued evolution toward wild-type sequences associated with increased sensitivity to chloroquine. For pfcrt K76T, by 2017 the prevalence of the wild type was >60% at all sites and >90% at 6 sites. For the pfmdr1 N86Y and D1246Y alleles, wild type prevalence ranged from 80 to 100%. We found low prevalence of K13 propeller domain mutations, which are associated with artemisinin resistance in Asia, but one mutation previously identified in northern Uganda, 675V, was seen in 2.0% of samples, including 5.5% of those from the 3 northernmost sites. Amplification of the pfmdr1 and plasmepsin2 genes, associated elsewhere with decreased sensitivity to lumefantrine and piperaquine, respectively, was seen in <1% of samples. For the antifolate targets pfdhfr and pfdhps, 5 mutations previously associated with resistance were very common, and the pfdhfr 164L and pfdhps 581G mutations associated with higher-level resistance were seen at multiple sites, although prevalence did not clearly increase over time. Overall, changes were consistent with the selective pressure of the national treatment regimen, artemether-lumefantrine, with increased sensitivity to chloroquine, and with poor efficacy of antifolates. Strong evidence for resistance to artemisinins was not seen. Continued surveillance of markers that predict antimalarial drug sensitivity is warranted.


Educational strategies for targeted retention of nonphysician health care providers.
This study examined the impact of a community-based, totally decentralized training program on the likelihood that graduates would establish their first practice within predefined and limited geographic regions. We found that when students in a physician assistant/nurse practitioner program received their preclinical and terminal training (preceptorship) in a region geographically proximate to their home residence, the likelihood that they would establish their first practice in that region was greatly increased. Similar results were found for students who took their preclinical training away from their home region but returned there for terminal training. Three additional training pathways were identified as being associated with markedly lower rates of regionally based graduate retention. Discriminant analysis was used to compare the relative impact of training and personal variables on retention. The educational process itself was found to be the single most important predictor of graduate retention. When structural variables were controlled, personal variables such as marital status, age, or sex had no predictive capabilities. With appropriate attention to the structural components of training--particularly terminal training (preceptorship)--experiences, PAs and NPs can be targeted to specific and relatively focused areas of medical need. These data suggest that several decentralized training strategies exist for physician assistants and nurse practitioners that would contribute to meeting health care delivery needs in chronically underserved areas.


Efficacy of femoral vascular closure devices in patients treated with anticoagulant, abciximab or thrombolytics during percutaneous endovascular procedures.
This study assessed the outcomes of using vascular closure devices following percutaneous transfemoral endovascular procedures in the patients who were treated with heparin, abciximab or thrombolytics (urokinase or t-PA) during the procedures. From March 28, 2003 to August 31, 2004, we conducted a prospective and randomized study in which 1,676 cases of 1,180 patients were treated with one of the two different closure devices (the collagen plug device was Angio-Seal; the suture-mediated closure device was The Closer S) at the femoral access site after instituting percutaneous endovascular procedures. Among the 1,676 cases, 108 cases (the drug group) were treated with heparin only (n = 94), thrombolytics only (n = 10), heparin and thrombolytics (n = 3), or abciximab and thrombolytics (n = 1) during the procedures; 1,568 cases (the no-drug group) were treated without any medication. We compared the efficacy and complications between the two groups. Of the drug group, 42 cases underwent arterial closures with the collagen plug devices and 66 cases underwent arterial closures with the suture-mediated closure devices. We also compared the efficacy and complications between these two groups. The immediate hemostasis rates were 92.9% (1,456/1,568) in the no-drug group and 91.7% (99/108) in the drug group. Early complications occurred in four cases of the drug group. These included two episodes of rebleeding with using the Closer S, which required manual compression for at least 10 minutes, and two episodes of minor oozing with using one Angio-Seal and one Closer S, which required two hours of additional bed rest. There was no late complication. So, the total success rates were 90.8% (1,423/1,568) in the no-drug group and 88.0% (95/108) in the drug group. These results were not significantly different between the two groups (p = 0.34). In the drug group, the difference of the successful hemostasis rate between the collagen plug devices and the suture-mediated devices was also not statistically significant (92.9% vs. 84.8%, respectively; p = 0.21). Arterial closure of the femoral access site with using vascular closure devices is both safe and effective, even in the patients who received heparin, abciximab or thrombolytics.


Personal Attitudes Toward Weight in Overweight and Obese US Hemodialysis Patients.
Overweight and obesity have become increasingly common among end-stage renal disease patients on hemodialysis. Yet, little attention has been given to what hemodialysis patients themselves think of their weight, how they perceive it affects their health, and their attitudes about or desire for weight reduction. We explored these issues using a survey that we designed specifically for the dialysis population. Sixty-six chronic hemodialysis patients from a US urban center with a body mass index ≥25 kg/m2 and stable weight were recruited to participate in a cross-sectional study. The 12-question weight-related survey was validated by retesting a random portion of the study population. Based on test-retest results, the survey had good to excellent validity. Seventy-nine percent of patients were black, 49% were male, 29% were overweight, and 71% were obese. In general, the patients underestimated their weight excess though 73% were interested in weight loss, of whom nearly half reported attempting to do so mostly through diet and exercise. The majority of participants interested in losing weight felt that doing so would improve their physical and emotional health. The most common barrier to weight reduction was a belief that it was too difficult (55%), followed by a lack of motivation, money, time, resources, and knowledge. Diet was the most common weight loss strategy (85%) considered, whereas bariatric surgery was the least common (6.1%). A majority of overweight and obese hemodialysis patients believe their excess weight is adversely impacting their health and quality of life and therefore wish to lose weight.


EAG-RS: A Novel Explainability-guided ROI-Selection Framework for ASD Diagnosis via Inter-regional Relation Learning.
Deep learning models based on resting-state functional magnetic resonance imaging (rs-fMRI) have been widely used to diagnose brain diseases, particularly autism spectrum disorder (ASD). Existing studies have leveraged the functional connectivity (FC) of rs-fMRI, achieving notable classification performance. However, they have significant limitations, including the lack of adequate information while using linear low-order FC as inputs to the model, not considering individual characteristics (i.e., different symptoms or varying stages of severity) among patients with ASD, and the non-explainability of the decision process. To cover these limitations, we propose a novel explainability-guided region of interest (ROI) selection (EAG-RS) framework that identifies non-linear high-order functional associations among brain regions by leveraging an explainable artificial intelligence technique and selects class-discriminative regions for brain disease identification. The proposed framework includes three steps: (i) inter-regional relation learning to estimate non-linear relations through random seed-based network masking, (ii) explainable connection-wise relevance score estimation to explore high-order relations between functional connections, and (iii) non-linear high-order FC-based diagnosis-informative ROI selection and classifier learning to identify ASD. We validated the effectiveness of our proposed method by conducting experiments using the Autism Brain Imaging Database Exchange (ABIDE) dataset, demonstrating that the proposed method outperforms other comparative methods in terms of various evaluation metrics. Furthermore, we qualitatively analyzed the selected ROIs and identified ASD subtypes linked to previous neuroscientific studies.


Making flexible magnetic aerogels and stiff magnetic nanopaper using cellulose nanofibrils as templates.
Nanostructured biological materials inspire the creation of materials with tunable mechanical properties. Strong cellulose nanofibrils derived from bacteria or wood can form ductile or tough networks that are suitable as functional materials. Here, we show that freeze-dried bacterial cellulose nanofibril aerogels can be used as templates for making lightweight porous magnetic aerogels, which can be compacted into a stiff magnetic nanopaper. The 20-70-nm-thick cellulose nanofibrils act as templates for the non-agglomerated growth of ferromagnetic cobalt ferrite nanoparticles (diameter, 40-120 nm). Unlike solvent-swollen gels and ferrogels, our magnetic aerogel is dry, lightweight, porous (98%), flexible, and can be actuated by a small household magnet. Moreover, it can absorb water and release it upon compression. Owing to their flexibility, high porosity and surface area, these aerogels are expected to be useful in microfluidics devices and as electronic actuators.


Protection against tumorigenesis by 3-methylcholanthrene in mice by beta-naphthoflavone as a function of inducibility of methylcholanthrene metabolism.
The noncarcinogenic enzyme inducer beta-naphthoflavone (beta-NF) causes an increase in both rate of activation and of detoxification of polycyclic aromatic hydrocarbon carcinogens in tissues of mice of induction-responsive strains. An experiment was carried out to test whether pretreatment with beta-NF would potentiate, protect against, or have no effect on the tumorigenicity of methylcholanthrene (MC) administered intragastrically to mice of varying responsiveness to induction of MC metabolism. The mouse strains used were C57BL/6, BALB/c, and C3H (inbred, highly responsive to induction), Swiss (random-bred, moderately responsive), and DBA/2 and AKR (inbred, nonresponsive). Twelve weekly treatments with 20 mg MC/kg intragastrically were preceded 24 h earlier each week by 150 mg beta-NF/kg i.p. or oil. Mice were killed when moribund or 1 year after start of treatment. During this period the beta-NF-pretreatment greatly reduced mortality due to cancer among the responsive inbred mice, by 100% for the C57BL/6, 89% for the BALB/c, and 65% for the C3H, compared with 50% for the Swiss, 23% for the DBA/2 and 0% for the AKR. There were significant reductions in MC-caused tumor incidences as a result of beta-NF pretreatment for: sarcomas, lymphomas, and forestomach and skin tumors for the C57BL/6 mice; sarcomas, mesotheliomas, and mammary carcinomas for the C3H mice; mesotheliomas for the BALB/c mice; sarcomas and tumors of the skin, forestomach, and lung for the Swiss mice; and lymphomas for the DBA/2 mice. beta-NF pretreatment did not cause an increase in the incidence of any type of tumor. These results are consistent with the conclusion that inducers of mixed function oxygenase activity generally provide protection against tumorigenesis by systemically administered polycyclic aromatic hydrocarbon carcinogens, probably by increasing rate of detoxification.


Lay beliefs about the preventability of major health conditions.
Beliefs about the extent to which health problems can be prevented reflect an understanding that preventive measures can reduce adverse health events and the level of control individuals perceive that they hold over the factors that affect their health. A population survey of 1659 people conducted in 1995 in south western Sydney, Australia, found that only child drownings, tooth decay, skin cancer, and burns and scalds were considered all or mostly preventable by more than 50% of the sample. The majority of respondents did not believe that heart attacks, cervical cancer, high blood pressure, serious road injury, lung cancer and asthma deaths were all or mostly preventable. Logistic regression analysis showed that people born in an English speaking country, those with more than 10 years of education and men were significantly more likely to recognize a number of key conditions as highly preventable. The findings suggest that, in spite of the range of prevention efforts in Australia to date, these are not matched by strong beliefs within the community that prevention is possible. Communication of the opportunities and methods for prevention needs to be improved, particularly among certain population groups. The findings also indicate a need to examine social and environmental factors which are potentially reducing confidence, and subsequently and adoption of preventive behaviours.


Radiographic manifestations of fibroblastic osteosarcoma: A diagnostic challenge.
Osteosarcoma is the most common primary bone tumor after plasma cell neoplasms. Osteosarcoma has diverse histological features and is characterized by the presence of malignant spindle cells and pluripotent neoplastic mesenchymal cells that produce immature bone, cartilage, and fibrous tissue. Osteosarcoma most frequently develops in the extremities of long bones, but can occur in the jaw in rare cases. The clinical and biological behavior of osteosarcoma of the jaw slightly differs from that of long-bone osteosarcoma. The incidence of jaw osteosarcoma is greater in the third to fourth decades of life, whereas long-bone osteosarcoma mostly occurs in the second decade of life. Osteosarcoma of the jaw has a lower tendency to metastasize and a better prognosis than long-bone osteosarcoma. Radiographically, osteosarcoma can present as a poorly-defined lytic, sclerotic, or mixed-density lesion with periosteal bone reaction response. Multi-detector computed tomography is useful for identifying the extent of bone destruction, as well as soft tissue involvement of the lesion. The current case report presents a fibroblastic osteosarcoma involving the left hemimandible with very unusual radiographic features.


Intratypic characterization of poliovirus type 1 isolates.
Intratypic serodifferentiation of 607 strains of poliovirus type 1 isolated from diverse epidemiological groups, was carried out using strain-specific antisera and monoclonal antibodies. The isolates were from patients of paralytic poliomyelitis from Marathwada (an epidemic area) and Bombay (endemic area) and from healthy children from Emmaneshwaram (vaccinated area). From Marathwada where mass scale vaccination with oral poliovirus vaccine (OPV) was performed to contain the spread of the epidemic, non-vaccine-like and vaccine-like virus strains were isolated. Only non-vaccine-like virus strains were detected among the Bombay isolates. In Emmaneshwaram mass-scale vaccination performed in 1986 had earlier led to the replacement of the wild poliovirus with the vaccine strains. However, even though systematic OPV immunization reached 93 per cent coverage in 1987 and 1988, majority of isolates from Emmaneshwaram were found to be non-vaccine-like. Results showed that routine immunization of children with OPV was not sufficient to displace the wild virus. A small number of antigenic variants were detected. The frequency of such variants was more when mass-scale vaccinations were performed after paralytic poliomyelitis outbreaks. Using a panel of monoclonal antibodies epitope mapping of these variants was performed.


Occurrence of Luteolin in the Greek Flora, Isolation of Luteolin and Its Action for the Treatment of Periodontal Diseases.
Higher plants possess the ability to synthesize a great number of compounds with many different functions, known as secondary metabolites. Polyphenols, a class of flavonoids, are secondary metabolites that play a crucial role in plant adaptation to both biotic and abiotic environments, including UV radiation, high light intensity, low/high temperatures, and attacks from pathogens, among others. One of the compounds that has received great attention over the last few years is luteolin. The objective of the current paper is to review the extraction and detection methods of luteolin in plants of the Greek flora, as well as their luteolin content. Furthermore, plant species, crop management and environmental factors can affect luteolin content and/or its derivatives. Luteolin exhibits various biological activities, such as cytotoxic, anti-inflammatory, antioxidant and antibacterial ones. As a result, luteolin has been employed as a bioactive molecule in numerous applications within the food industry and the biomedical field. Among the different available options for managing periodontitis, dental care products containing herbal compounds have been in the spotlight owing to the beneficial pharmacological properties of the bioactive ingredients. In this context, luteolin's anti-inflammatory activity has been harnessed to combat periodontal disease and promote the restoration of damaged bone tissue.


Effects of repeated adolescent exposure to cannabis smoke on cognitive outcomes in adulthood.
Cannabis (marijuana) is the most widely used illicit drug in the USA, and consumption among adolescents is rising. Some animal studies show that adolescent exposure to delta 9-tetrahydrocannabinol or synthetic cannabinoid receptor 1 agonists causes alterations in affect and cognition that can persist into adulthood. It is less clear, however, whether similar alterations result from exposure to cannabis via smoke inhalation, which remains the most frequent route of administration in humans. To begin to address these questions, a rat model was used to determine how cannabis smoke exposure during adolescence affects behavioral and cognitive outcomes in adulthood. Adolescent male Long-Evans rats were assigned to clean air, placebo smoke, or cannabis smoke groups. Clean air or smoke exposure sessions were conducted daily during adolescence (from P29-P49 days of age ) for a total of 21 days, and behavioral testing began on P70. Compared to clean air and placebo smoke conditions, cannabis smoke significantly attenuated the normal developmental increase in body weight, but had no effects on several measures of either affect/motivation (open field activity, elevated plus maze, instrumental responding under a progressive ratio schedule of reinforcement) or cognition (set shifting, reversal learning, intertemporal choice). Surprisingly, however, in comparison to clean air controls rats exposed to either cannabis or placebo smoke in adolescence exhibited enhanced performance on a delayed response working memory task. These findings are consistent with a growing body of evidence for limited long-term adverse cognitive and affective consequences of adolescent exposure to relatively low levels of cannabinoids.


Hereditary ovarian cancers: from BRCA mutations to clinical management. A modern appraisal.
In the past few years, ovarian cancer research has focused increasingly on disease prevention; but an increasing number of women refer to gynecology and clinical genetics clinics with a family history of ovarian cancer and inherited familial mutations. The interest on the issue has increased also due to the identification of BReast CAncer1 (BRCA1) and BRCA2 genes mutations. The importance of recognizing the characteristics of hereditary ovarian cancer (HOC) and manage women at risk appropriately will provide more accurate care of the high-risk population. Women at risk can be identified by pedigree analysis and may receive counseling from interdisciplinary cancer genetics clinics, while those at high risk need to receive genetic testing. Risk calculation programs define risks and assist in decision-making in clinical options and genetic testing; they provide information on the risks of the disease, mutation status, and the use of genetic testing in the management of high-risk families. Furthermore, while a large number of surrogate preliminary markers have been identified, there are still limited studies on ovarian cancer genomics. Different options for risk management of HOC are available: surveillance, chemoprevention and prophylactic surgery. Surveillance in HOC high-risk patients is still not accurate. Chemoprevention is currently a controversial topic, because a number of major issues still need to be addressed in developing and testing agents for ovarian cancer chemoprevention. Prophylactic surgery has been shown to effectively decrease cancer risk, and it has the possibility to substantially reduce ovarian cancer mortality.


Genetic assembly and selective toxicity of diphtheria-toxin-related polypeptide hormone fusion proteins.
The reports of Miyanohara et al. (1986) and Murphy et al. (1986) were the first to describe the genetic construction, expression, and receptor-specific selective toxicity of a chimaeric toxin. In the present report, we have extended these earlier observations and have shown that the fusion of a modified gene encoding IL-2 to a truncated diphtheria toxin gene also results in the expression of a biologically active chimaeric IL-2 toxin. In both instances we have used receptor-binding-domain substitution and have genetically coupled those portions of the diphtheria toxin structural gene that encode the ADP-ribosyl transferase activity of fragment A and lipid-associating domains of fragment B to modified genes which encode either the polypeptide hormone alpha-MSH or the T-cell growth factor IL-2. The chimaeric toxins expressed from these gene fusions have been shown to be selectively targeted to those eukaryotic cells that carry specific surface receptors for the ligand compounds of the hybrid. For example, in the case of the IL-2 toxin, it is clear that the selective action of this hybrid protein is based upon both its diphtheria-toxin and IL-2-related components. Following binding to the IL-2R on activated and/or malignant T-cell, IL-2 toxin is internalized by receptor-mediated endocytosis. Upon acidification of the endosome, diphtheria toxin fragment B portions of the chimaeric toxin facilitate the delivery of fragment A to the cytosol where it catalyses the ADP ribosylation of EF-2. The assembly of chimaeric toxins at the level of the gene offers several advantages over chemical linkage. Since chemical linkage of the toxophore and ligand components of the conjugate toxins requires activation of the epsilon-amino moiety of lysine residues with reagents that will allow for subsequent disulphide linkage, the precise site of coupling is generally not known. In addition, there has been considerable concern over the lability of the disulphide bond between the toxophore and ligand components in vivo due to the action of disulphide reductases. The assembly of chimaeric toxins at the level of the gene allows for precise linkage of the toxophore and ligand components. Since the linkage between the toxophore and ligand is a peptide bond, the chimaeric toxin should be stable in vivo. In addition, the genetic construction of chimaeric toxins also allows for further protein engineering through site-directed mutagenesis.(ABSTRACT TRUNCATED AT 400 WORDS)


Applications of daunorubicin-loaded PLGA-PLL-PEG-Tf nanoparticles in hematologic malignancies: an in vitro and in vivo evaluation.
With the development of drug delivery, novel tools and technological approaches have captured the attention of researchers in recent years. Several target drug delivery systems (DDSs) including nanoparticles (NPs) have been developed as an important strategy to deliver classical medicine. The objective of this study was to evaluate the application of novel daunorubicin (DNR)-loaded poly(lactic-co-glycolic acid)-poly-l-lysine-polyethylene glycol-transferrin (Tf) nanoparticles (DNR-loaded NPs) in hematologic malignancies in vitro and in vivo. DNR-loaded NPs were prepared by the modified double-emulsion solvent evaporation/diffusion method, and its microscopic form was observed under scanning electron microscope. Intracellular distribution of DNR was directly detected by fluorescence microscopy. After establishment of a tumor xenograft model by injecting K562 cells into the left leg of nude mice, the therapeutic effect of the DNR-loaded NPs on the growth of tumors was measured by calculating the tumor size, and the relative expression of Caspase-3 protein was detected by immunohistochemical staining. Furthermore, intracellular concentration of DNR and the extent of cell apoptosis in primary leukemia cells were quantified by flow cytometry. DNR-loaded NPs had a spherical shape of about 180 nm in diameter. DNR-loaded NP group showed a significant enhancement of cellular uptake in K562 cells compared with DNR group. Tumor inhibition rate was higher in DNR-loaded NP group in comparison with DNR group, and the relative expression of Caspase-3 protein was upregulated in DNR-loaded NP group compared with DNR group. Furthermore, DNR-loaded NPs obviously increased intracellular concentration of DNR in primary leukemia cells compared with DNR group, but there was no significant difference in primary cell apoptosis between the two groups. These findings suggest that the novel NP DDS can enhance the performance of conventional antitumor drugs and may be suitable for further application in the treatment of hematologic malignancies.