Identification of a potent and selective noncovalent cathepsin S inhibitor.
Cathepsin S is considered crucial for normal presentation of major histocompatibility complex (MHC) class II-restricted antigens by antigen presenting cells to CD4+ T cells. It is a key enzyme for the degradation of the class II-associated invariant chain, a process that is required for effective antigen loading of class II molecules. Here, we report a selective, orally available, high-affinity cathepsin S inhibitor, 1-[3-[4-(6-Chloro-2,3-dihydro-3-methyl-2-oxo-1H-benzimidazol-1-yl)-1-piperidinyl]propyl]-4,5,6,7-tetrahydro-5-(methylsulfonyl)-3-[4-(trifluoromethyl)phenyl]-1H-pyrazolo[4,3-c]pyridine. (JNJ 10329670), that represents a novel class of immunosuppressive compounds. JNJ 10329670 is a highly potent (Ki of approximately 30 nM), nonpeptidic, noncovalent inhibitor of human cathepsin S, but it is much less active against the mouse, dog, monkey, and bovine enzymes. The compound is inactive against other proteases, including the closely related cathepsins L, F, and K. This selectivity makes JNJ 10329670 an excellent tool for exploring the role of cathepsin S in human systems. Treatment of human B cell lines and primary human dendritic cells with JNJ 10329670 resulted in the accumulation of the p10 fragment of the invariant chain (IC50 of approximately 1 microM). In contrast, inhibition of invariant chain proteolysis was much less effective in a human monocytic cell line, suggesting that other enzymes may degrade the invariant chain in this cell type. JNJ 10329670 was shown to block the proteolysis of the invariant chain in vivo by using immunocompromised mice injected with human peripheral blood mononuclear cells (PBMCs). Furthermore, this inhibitor blocks the presentation of tetanus toxoid and giant ragweed by human PBMCs. The properties of JNJ 10329670 make it a candidate for immunosuppressive therapy of allergies and autoimmune diseases.


Contribution of IL-1 to resistance to Streptococcus pneumoniae infection.
The role of IL-1 in susceptibility to Streptococcus pneumoniae infection was studied in mice deficient in genes of the IL-1 family [i.e. IL-1alpha-/-, IL-1beta-/-, IL-1alpha/beta-/- and IL-1R antagonist (IL-1Ra)-/- mice] following intra-nasal inoculation. Intra-nasal inoculation of S. pneumoniae of IL-1beta-/- and IL-1alpha/beta-/- mice displayed significantly lower survival rates and higher nasopharyngeal and lung bacterial load as compared with control, IL-1alpha-/- and IL-1Ra-/- mice. Treatment of IL-1beta-/- mice with rIL-1beta significantly improved their survival. A significant increase in blood neutrophils was found in control, IL-1alpha-/- and IL-1Ra-/- but not in IL-1beta-/- and IL-1alpha/beta-/- mice. Local infiltrates of neutrophils and relatively preserved organ architecture were observed in the lungs of IL-1alpha-/- and control mice. However, S. pneumoniae-infected IL-1beta-/-, IL-1alpha/beta-/- and IL-1Ra-/- mice demonstrated diffuse pneumonia and tissue damage. Altogether, all three isoforms contribute to protection against S. pneumoniae; our results point to differential role of IL-1alpha and IL-1beta in the pathogenesis and control of S. pneumoniae infection and suggest that IL-1beta has a major role in resistance to primary pneumococcal infection while the role of IL-1alpha is less important.


[Sexual behavior in higher age].
Apart from other factors the sexual behaviour of man and woman depends also on age. Like other physiological conditions the sexual function underlies changes according to age, representing themselves in slowed down sexual reaction, diminished intensity of orgasm and ejaculation as well as decreased libido. In general the sexual activity of both sexes is diminishing after the 50th year of life, simultaneously showing that the sexual function in man more easily becomes disturbed--not so in woman.


Reproducibility of free-breathing cardiovascular magnetic resonance coronary angiography.
Contemporary free-breathing non contrast enhanced cardiovascular magnetic resonance angiography (CMRA) was qualitatively and quantitatively evaluated to ascertain the reproducibility of the method for coronary artery luminal dimension measurements. Twenty-two healthy volunteers (mean age 32 +/- 7 years, 12 males) without coronary artery disease were imaged at 2 centers (1 each in Europe and North America) using navigator-gated and corrected SSFP CMRA on a commercial whole body 1.5T System. Repeat images of right (RCA, n = 21), left anterior descending (LAD, n = 14) and left circumflex (LCX, n = 14) coronary arteries were obtained in separate sessions using identical scan protocol and imaging parameters. True visible vessel length, signal-to-noise (SNR), contrast-to-noise ratios (CNR) and the average luminal diameter over the first 4 cm of the vessel were measured. Intra-observer, inter-observer and inter-scan reproducibility of coronary artery luminal diameter were determined using Pearson's correlation, Bland-Altman analysis and intraclass correlation coefficients (ICC). CNR, SNR and the mean length of the RCA, LAD and LCX imaged for original and repeat scans were not significantly different (all p > 0.30). There was a high degree of intra-observer, inter-observer and inter-scan agreements for RCA, LAD and LCX luminal diameter respectively on Bland-Altman and ICC analysis (ICC's for RCA: 0.98. 0.98 and 0.86; LAD: 0.89, 0.89 and 0.63; LCX: 0.95, 0.94 and 0.79). In a 2-center study, we demonstrate that free-breathing 3D SSFP CMRA can visualize long continuous segments of coronary vessels with highly reproducible measurements of luminal diameter.


Transcription factor Stat5 is an early marker of differentiation of murine embryonic stem cells.
Embryonic stem (ES) cells are pluripotent descendants of the inner cell mass of blastocysts capable of differentiating into progenitor cells of most if not all tissues. The pluripotency of ES cells is maintained by leukemia inhibitory factor (LIF), a member of the family of interleukin-6-type cytokines. These cytokines activate Janus tyrosine kinases and signal transducer and activator of transcription factors (Stat) via the signalling receptor component gp130. Pluripotent ES1 cells proliferating in the presence of LIF were known from previous studies to contain Stat3 and Stat1 capable of transcriptional activation. Here we report that the level of tyrosine-phosphorylated Stat3 decreases rapidly during differentiation induced by treatment of ES1 cells either with retinoic acid (RA) or by withdrawal of LIF. In line with this finding, the DNA-binding activity of Stat3 decreased during differentiation. In contrast, Stat5 was absent from pluripotent proliferating ES cells, but appeared early after induction of differentiation. The positive correlation between induction of differentiation and expression of Stat5 mRNA was confirmed for three independent ES cell lines. Stat5 transcripts were detectable in ES1 cells as early as 12 h after treatment with RA and 36 h after withdrawal of LIF. Stat5 protein was detectable 2 days after the onset of differentiation. These results establish Stat5 as a novel marker of very early stages of differentiation of ES cells.


An overview of statistical methods for multiple failure time data in clinical trials.
In a long term clinical trial to evaluate a new treatment, quite often each study subject may experience a number of 'failures' that correspond to repeated occurrences of the same type of event or events of entirely different natures during his/her follow-up period. To obtain efficient inference procedures for the therapeutic effect over time, it is desirable to utilize those multiple event times in the analysis. In this article, we review some useful procedures for analysing different kinds of multivariate failure time data. Specifically, we discuss the two-sample problems and the general regression problems with various survival models. We also give some recommendations of appropriate procedures for each type of multiple event data structure for practical usage.


Whole genome association mapping of plant height in winter wheat (Triticum aestivum L.).
The genetic architecture of plant height was investigated in a set of 358 recent European winter wheat varieties plus 14 spring wheat varieties based on field data in eight environments. Genotyping of diagnostic markers revealed the Rht-D1b mutant allele in 58% of the investigated varieties, while the Rht-B1b mutant was only present in 7% of the varieties. Rht-D1 was significantly associated with plant height by using a mixed linear model and employing a kinship matrix to correct for population stratification. Further genotyping data included 732 microsatellite markers, resulting in 770 loci, of which 635 markers were placed on the ITMI map plus a set of 7769 mapped SNP markers genotyped with the 90 k iSELECT chip. When Bonferroni correction was applied, a total of 153 significant marker-trait associations (MTAs) were observed for plant height and the SSR markers (-log10 (P-value) ≥ 4.82) and 280 (-log10 (P-value) ≥ 5.89) for the SNPs. Linear regression between the most effective markers and the BLUEs for plant height indicated additive effects for the MTAs of different chromosomal regions. Analysis of syntenic regions in the rice genome revealed closely linked rice genes related to gibberellin acid (GA) metabolism and perception, i.e. GA20 and GA2 oxidases orthologous to wheat chromosomes 1A, 2A, 3A, 3B, 5B, 5D and 7B, ent-kaurenoic acid oxidase orthologous to wheat chromosome 7A, ent-kaurene synthase on wheat chromosome 2B, as well as GA-receptors like DELLA genes orthologous to wheat chromosomes 4B, 4D and 7A and genes of the GID family orthologous to chromosomes 2B and 5B. The data indicated that besides the widely used GA-insensitive dwarfing genes Rht-B1 and Rht-D1 there is a wide spectrum of loci available that could be used for modulating plant height in variety development.


Episodic defoliation rapidly reduces starch but not soluble sugars in an invasive shrub, Tamarix spp.
Plants rely on pools of internal nonstructural carbohydrates (NSCs: soluble sugars plus starch) to support metabolism, growth, and regrowth of tissues damaged from disturbance such as foliage herbivory. However, impacts of foliage herbivory on the quantity and composition of NSC pools in long-lived woody plants are currently unclear. We implemented a controlled defoliation experiment on mature Tamarix spp.-a dominant riparian woody shrub/tree that has evolved with intense herbivory pressure-to test two interrelated hypotheses: (1) Repeated defoliation disproportionately impacts aboveground versus belowground NSC storage. (2) Defoliation disproportionately impacts starch versus soluble sugar storage. Hypotheses were tested by transplanting six Tamarix seedlings into each of eight cylinder mesocosms (2 m diameter, 1 m in depth). After 2.5 years, plants in four of the eight mesocosms were mechanically defoliated repeatedly over a single growing season, and all plants were harvested in the following spring. Defoliation had no impact on either above- or belowground soluble sugar pools. However, starch in defoliated plants dropped to 55% and 26% in stems and roots, respectively, relative to control plants, resulting in an over 2-fold higher soluble sugar to starch ratio in defoliated plants. The results suggest that defoliation occurring over a single growing season does not impact immediate plant functions such as osmoregulation, but depleted starch could limit future fitness, particularly where defoliation occurs over multiple years. These results improve our understanding of how woody plants cope with episodic defoliation caused by foliage herbivory and other disturbances.


Metastasis of breast lobular carcinoma in a cervical leiomyoma.
We report here a case of 40-year-old female admitted in view of bilateral ovarian tumors. There was past history of modified radical mastectomy. CT scan revealed a uterine cervicalfibroid in addition to bilateral adnexal masses. Lobular carcinoma metastasis were seen in the leiomyoma as well as in the bilateral ovaries. Metastasis of ductal carcinoma to uterine leiomyoma have been reported in literature. The present case is unique in two ways--(1) metastasis of lobular carcinoma (2) occurring in a cervical leiomyoma.


Impact of coronavirus disease 2019 on head and neck urgent suspected cancer referral pathways in rural Wales.
To assess the impact of the coronavirus disease 2019 pandemic on head and neck urgent suspected cancer referral pathways in rural areas of Wales. A retrospective audit was conducted of 2234 head and neck urgent suspected cancer referrals received from January 2019 to November 2020. The referrals dropped by 35 per cent in 2020 compared to the same period in 2019. The time from general practitioner referral to the first ENT appointment improved during the pandemic (8.0 vs 10.0 days; p < 0.001). Of referrals, 92.1 per cent were seen within a 14-day period in 2020, compared with 79.6 per cent in 2019 (p < 0.001). There were no differences between 2020 and 2019 in terms of: the (confirmed cancer) conversion rate (10.6 per cent vs 9.7 per cent; p = 0.60), general practitioner referral to multidisciplinary team discussion time (35.5 vs 41.5 days; p = 0.40) or general practitioner referral to initiation of treatment time (68.0 vs 78.0 days; p = 0.16). Whilst coronavirus disease 2019 reduced the number of overall head and neck urgent suspected cancer referrals, the pathways were generally unchanged, if not slightly improved, in rural Wales.


A new sesarmid crab of the genus Karstarma (Crustacea: Decapoda: Brachyura) associated with limestone formations in East Java, Indonesia.
A new stygobitic sesarmid crab species is described from underground freshwater cave streams in the southern Malang karst range on the south coast of East Java Province, Indonesia. Karstarma malang n. sp. is morphologically most similar to K. jacobsoni (Ihle, 1912) from an underground river cave system in the southern coast of the Special Region of Yogyakarta Province in central Java, but differs in having a relatively larger cornea, less swollen ocular peduncle which lacks a ridge along the median part, proportionately shorter ambulatory legs and a more slender male first gonopod. This paper increases the number of the species of Karstarma Davie Ng, 2007, to 16; the new species being the eighth of the genus from Indonesia. It is also the third species which has a distinctly reduced cornea.


Job satisfaction in nursing: a concept analysis study.
This study aims to undertake a concept analysis of job satisfaction in the nursing profession. Around current global shortage of nurses, it is important to stabilize the nursing workforce. Nurses' job satisfaction has been found to be related to intention to leave. In the nursing profession, there is a lack of evidence to support the attributes of nurses' job satisfaction. Walker and Avant's approach of concept analysis was used. The main attributes of job satisfaction from this study are (1) fulfillment of desired needs within the work settings, (2) happiness or gratifying emotional responses towards working conditions, and (3) job value or equity. These attributes are influenced by antecedent conditions like demographic, emotional, work characteristics and environmental variables. Additionally, the consequences of nurses' job satisfaction have a significant impact on both nurses and patients. This study integrated both the content and process of motivational theories to generate the attributes of job satisfaction in nursing that overcome the limitation of the previous studies, which looked only at the definitions of nurses' job satisfaction based on content motivational theories. The findings of this study can facilitate both nursing researchers to develop a cultural adaption instrument and policy makers to improve clinical nursing practice. This analysis provides nurse managers with a new perspective to deal with nurses' job satisfaction by taking into account all the attributes that influence it in the nursing field.


Laparoscopic pancreaticojejunostomy using a barbed suture: a novel technique.
The adoption of laparoscopy for the Whipple procedure remains limited in part by its technical difficulty. We sought to develop a superior, simpler pancreaticojejunostomy technique. We applied a running barbed suture (V-Loc™; Covidien, Mansfield, MA) to perform the pancreaticojejunostomy over a stent placed in the pancreatic duct and a small enterotomy in the jejunum. This technique was attempted in the last 19 of 37 patients presenting to two surgeons (M.A.M. and B.H.E.) for a laparoscopic Whipple procedure. Data were collected on operative time, pancreatic leak events, and related complications. We successfully applied the modified technique in all 19 patients. Pancreatic leak occurred in 5% of patients with the modified technique (Grade A=0; Grade B=1; Grade C=0) and 11% with the standard technique (Grade A=1; Grade B=1; Grade C=0). All leaks were managed with external drainage. There were no leak-related complications. Mean operative time was shorter for the modified technique (mean, 367 minutes; range, 260-576 minutes) than the standard technique (mean, 440 minutes; range, 300-665 minutes). The use of a running barbed suture for laparoscopic pancreaticojejunostomy is a safe and efficient technique. Our operative times were decreased with this technique, and our outcomes were similar to other laparoscopic Whipple series.


Calpain inhibition stabilizes the platelet proteome and reactivity in diabetes.
Platelets from patients with diabetes are hyperreactive and demonstrate increased adhesiveness, aggregation, degranulation, and thrombus formation, processes that contribute to the accelerated development of vascular disease. Part of the problem seems to be dysregulated platelet Ca(2+) signaling and the activation of calpains, which are Ca(2+)-activated proteases that result in the limited proteolysis of substrate proteins and subsequent alterations in signaling. In the present study, we report that the activation of μ- and m-calpain in patients with type 2 diabetes has profound effects on the platelet proteome and have identified septin-5 and the integrin-linked kinase (ILK) as novel calpain substrates. The calpain-dependent cleavage of septin-5 disturbed its association with syntaxin-4 and promoted the secretion of α-granule contents, including TGF-β and CCL5. Calpain was also released by platelets and cleaved CCL5 to generate a variant with enhanced activity. Calpain activation also disrupted the ILK-PINCH-Parvin complex and altered platelet adhesion and spreading. In diabetic mice, calpain inhibition reversed the effects of diabetes on platelet protein cleavage, decreased circulating CCL5 levels, reduced platelet-leukocyte aggregate formation, and improved platelet function. The results of the present study indicate that diabetes-induced platelet dysfunction is mediated largely by calpain activation and suggest that calpain inhibition may be an effective way of preserving platelet function and eventually decelerating atherothrombosis development.


Reasons for delay in inpatient admission at an emergency department.
This study highlighted the reasons which contributed to longer stay of patients in Emergency Department (ED) who were advised admission. This study was conducted from August 4 to 11, 2004G as a retrospective review of the ED cards of patients admitted to inpatients wards of Al-Noor Specialist Hospital, Makkah, Saudi Arabia. The demographic data, doctors & nurses notes with their timings were reviewed. The maximum consumed time by a reason was considered as the main reason of delay for that subject. The delayed patients were divided into Group A and B, delayed before and after admission was advised, respectively. Prolonged length of stay (Delay) in ED was defined as stay longer than 2 hours after patient's arrival in ED until they were received to wards. Out of total 4876 visits during study period, 355 (7.3%) patients were admitted, and 238 (67%) were delayed. Age group 13-30 years was common in delayed 78 (32.8%) and not delayed 56 (47.9%) subjects. The mean length of stay of delayed subjects was 256 minutes. Group A 146 (61.4%) had more subjects than group B 92 (38.6%) (p < 0.001). Fifty eight (39.7%) patients stayed between 2-3hours in Group A vs. B 23 (25%) (OR 2, 95% CI 1.1-3.5). Common reason of delay in Group A was multiple consultations with further investigations 70 (48%) (p < 0.001) while file making process was common 40 (43.5%) in group B (p < 0.001). Out of admitted patients 67% were delayed mainly due to late advised admission with major reason of delay were multiple consultations.


Endothelial Hey2 deletion reduces endothelial-to-mesenchymal transition and mitigates radiation proctitis in mice.
The current study evaluated the role of Hey2 transcription factor in radiation-induced endothelial-to-mesenchymal transition (EndoMT) and its impact on radiation-induced tissue damage in mice. Phenotypic modifications of irradiated, Hey2 siRNA- and Hey2 vector plasmid-transfected human umbilical vein endothelial cells (HUVECs) resembling EndoMT were monitored by qPCR, immunocytochemistry and western blots. Subsequently, in mice, a Cre-LoxP strategy for inactivation of Hey2 specifically in the endothelium was used to study the biological consequences. Total body irradiation and radiation proctitis were monitored to investigate the impact of conditional Hey2 deletion on intestinal stem cells and microvascular compartment radiosensitivity, EndoMT and rectal damage severity. We found that EndoMT occurs in irradiated HUVECs with concomitant Hey2 mRNA and protein increase. While Hey2 silencing has no effect on radiation-induced EndoMT in vitro, Hey2 overexpression is sufficient to induce phenotypic conversion of endothelial cells. In mice, the conditional deletion of Hey2 reduces EndoMT frequency and the severity of rectal tissue damage. Our data indicate that the reduction in mucosal damage occurs through decline in stem/clonogenic epithelial cell loss mediated by microvascular protection. EndoMT is involved in radiation proctitis and this study demonstrates that a strategy based on the reduction of EndoMT mitigates intestinal tissue damage.


High-Throughput Docking Using Quantum Mechanical Scoring.
Today high-throughput docking is one of the most commonly used computational tools in drug lead discovery. While there has been an impressive methodological improvement in docking accuracy, docking scoring still remains an open challenge. Most docking programs are rooted in classical molecular mechanics. However, to better characterize protein-ligand interactions, the use of a more accurate quantum mechanical (QM) description would be necessary. In this work, we introduce a QM-based docking scoring function for high-throughput docking and evaluate it on 10 protein systems belonging to diverse protein families, and with different binding site characteristics. Outstanding results were obtained, with our QM scoring function displaying much higher enrichment (screening power) than a traditional docking method. It is acknowledged that developments in quantum mechanics theory, algorithms and computer hardware throughout the upcoming years will allow semi-empirical (or low-cost) quantum mechanical methods to slowly replace force-field calculations. It is thus urgently needed to develop and validate novel quantum mechanical-based scoring functions for high-throughput docking toward more accurate methods for the identification and optimization of modulators of pharmaceutically relevant targets.


Closed incision prophylactic negative pressure wound therapy in patients undergoing major complex abdominal wall repair.
To evaluate if incisional prophylactic negative pressure wound therapy (pNPWT) reduces wound infections and other wound complications in high-risk patients undergoing major complex ventral abdominal wall repair. Retrospective before-after comparison nested in a consecutive series of patients undergoing elective major complex abdominal wall repair. Starting January 2014, pNPWT was applied on the closed incisional wound for a minimum of 5 days. To minimize selection bias, we compared two periods of 14 months before and after January 2014. Wound infections according to the Centre for Disease Control Surgical Site Infection classification as well as other wound complications were recorded. Thirty-two patients were included in the pNPWT group and 34 in the control group. The study group involved clean-contaminated and contaminated operations due to enterocutaneous fistula, enterostomies or infected mesh. Median duration of pNPWT was 5 days (IQR 5-7). Overall wound infection rate was 35%. pNPWT was associated with a significant decrease in postoperative wound infection rate (24 versus 51%; p = 0.029, OR 0.30 (95% CI 0.10-0.90)). Incisional wound infection rates dropped from 48 to 7% (p < 0.01, OR 0.08 (95% CI 0.16-0.39), whereas the number of subcutaneous abscesses was comparable in both groups. Moreover, less interventions were needed in the pNPWT group (p < 0.001). Closed incision pNPWT seems a promising solution to reduce the incidence of wound infections in complex abdominal wall surgery. Randomized controlled trials are needed to estimate more precisely the value and cost-effectiveness of pNPWT in this high-risk setting.


The role of an autoantigen, histidyl-tRNA synthetase, in the induction and maintenance of autoimmunity.
Patients with systemic autoimmune diseases make specific autoantibodies that are directed against self structures. According to one view, these autoantibodies arise as a result of an immune response to foreign antigens such as infectious agents that share, by molecular mimicry, common structures with host proteins. An alternative view is that the target autoantigen itself initiates, selects, and sustains autoantibody synthesis. We show here that anti-Jo-1 autoantibodies directed against histidyl-tRNA synthetase in the human autoimmune muscle disease polymyositis undergo, in addition to spectrotype broadening and class switching, the sine qua non of an immune response to the target antigen--affinity maturation to that antigen. We demonstrate further that these autoantibodies, unlike anti-synthetase antibodies induced in mice immunized with heterologous antigen, bind only nonlinear epitopes on the native human synthetase that remain exposed when the enzyme is complexed to tRNA(His). These data suggest that the native target autoantigen itself has played a direct role in selecting and sustaining the autoantibody response and sharply restrict the time and the way in which a molecular mimic might act to provoke autoantibodies.


Comparison of polyethylene glycol 3350 and lactulose for treatment of chronic constipation in children.
Polyethylene glycol (PEG) 3350 and lactulose were compared in an unblinded, randomized, crossover design for treatment of constipation in 37 children aged 2 to 16 years. Subjects received lactulose (1.3 g/kg/d divided twice daily up to 20 g) or PEG 3350 (10 g/m2/day) for 2 weeks. PEG 3350 significantly decreased the total colonic transit time compared to lactulose (47.6+/-2.7 vs 55.3+/-2.4 hours, mean +/- SE, PEG 3350 vs lactulose, respectively, p = 0.038). The stool frequency, form, and the ease of passage were similar for each laxative. Polyethylene glycol 3350 is an effective laxative for the treatment of chronic constipation in children.


The first Brevinin-1 antimicrobial peptide with LPS-neutralizing and anti-inflammatory activities in vitro and in vivo.
Antimicrobial peptide is one important component of the first protective barrier of organisms. They not only have potent antimicrobial activity which can protect the body from the invading pathogens, but also participate in the immune regulation of the body. In this study, a Brevinin-1 peptide named by Brevinin-1GHd was identified from Hoplobatrachus rugulosus, and the similarity of mature peptide sequence among Brevinin-1GHd, Brevinin-1HL and Brevinin-1GHa supported the close species relationship between H. rugulosus, Hylarana latouchii and Hylarana guertheri. Moreover, the secondary structure of Brevinin-1GHd was found to possess α-helical characteristics and high thermal stability. In addition, Brevinin-1GHd could bind to LPS with a Kd value of 6.49 ± 5.40 mM and suppress the release of TNF-α, NO, IL-6 and IL-1β by inactivation of MAPK signaling pathway in RAW 264.7 cells induced by LPS. Furtherly, Brevinin-1GHd had a significant inhibitory effect on acute edema development in the right paw of mice injected by carrageenan. Thus, the significant LPS-neutralizing and anti-inflammatory activities of Brevinin-1GHd were demonstrated in this study, which made it become the first Brevinin-1 family peptide with anti-inflammatory activity reported so far, and the biological activity of Brevinin-1GHd made it promising to be a novel therapeutic drug for infectious inflammation.


Two-Dimensional Covalent Organic Framework (COF) Membranes Fabricated via the Assembly of Exfoliated COF Nanosheets.
Exceptionally homogeneous and ultrathin COF membranes were successfully fabricated using exfoliated COF nanosheets with uniform perforations as membrane building blocks. The COF membranes showed highly permeable performance due to the ultrafast molecular diffusion through the perforations of the COF nanosheets and the excellent thermal stability due to the robust covalent bonds in the framework.


Association of 14-bp insertion/deletion polymorphism of HLA-G gene with unexplained recurrent spontaneous abortion: a meta-analysis.
A meta-analysis was performed to assess the association of the human leukocyte antigen-G (HLA-G) 14 bp insertion (ins)/deletion (del) polymorphism with unexplained recurrent spontaneous abortions (URSA). The fixed or random effect pooled measure was selected based on the homogeneity test among studies that was evaluated with I². Odds ratio (OR) with 95% confidence interval (CI) was used to assess the strength of the association. In this meta-analysis, 14 studies with 1464 cases and 1247 controls corresponded to the inclusion criteria were included. Significant associations between 14 bp ins/del polymorphism and risk of URSA were observed in both dominant [random effect model (REM) OR = 1.469, 95% CI = 1.127-1.914] and codominant (REM OR = 1.195, 95% CI = 1.005-1.420) models. After excluding two articles that deviated from Hardy-Weinberg equilibrium in cases and sensitivity analysis, significant associations were also observed in dominant [fixed effect model (FEM) OR = 1.224, 95% CI = 1.020-1.470] and codominant (FEM OR = 1.158, 95% CI = 1.028-1.305) models. This meta-analysis suggests that the 14 bp ins HLA-G allele is associated with increased risk of URSA. The results are of importance to the clinical practice of URSA and infertility.


Fossil and genomic evidence constrains the timing of bison arrival in North America.
The arrival of bison in North America marks one of the most successful large-mammal dispersals from Asia within the last million years, yet the timing and nature of this event remain poorly determined. Here, we used a combined paleontological and paleogenomic approach to provide a robust timeline for the entry and subsequent evolution of bison within North America. We characterized two fossil-rich localities in Canada's Yukon and identified the oldest well-constrained bison fossil in North America, a 130,000-y-old steppe bison, Bison cf. priscus We extracted and sequenced mitochondrial genomes from both this bison and from the remains of a recently discovered, ∼120,000-y-old giant long-horned bison, Bison latifrons, from Snowmass, Colorado. We analyzed these and 44 other bison mitogenomes with ages that span the Late Pleistocene, and identified two waves of bison dispersal into North America from Asia, the earliest of which occurred ∼195-135 thousand y ago and preceded the morphological diversification of North American bison, and the second of which occurred during the Late Pleistocene, ∼45-21 thousand y ago. This chronological arc establishes that bison first entered North America during the sea level lowstand accompanying marine isotope stage 6, rejecting earlier records of bison in North America. After their invasion, bison rapidly colonized North America during the last interglaciation, spreading from Alaska through continental North America; they have been continuously resident since then.


Heat and pressure treatments effects on peanut allergenicity.
Peanut allergy is recognized as one of the most severe food allergies. The aim of this study was to investigate the changes in IgE binding capacity of peanut proteins produced by thermal-processing methods, including autoclaving. Immunoreactivity to raw and thermally processed peanut extracts was evaluated by IgE immunoblot and skin prick test in patients with clinical allergy to peanut. Roasted peanut and autoclaved roasted peanut were selected for IgE ELISA experiments with individual sera, immunoblot experiments with antibodies against peanut allergens (Ara h 1, Ara h 2 and Ara h 3), digestion experiments, and circular dichroism spectroscopy. In vitro and in vivo experiments showed IgE immunoreactivity of roasted peanut proteins decreased significantly at extreme conditions of autoclaving. Circular dichroism experiments showed unfolding of proteins in autoclave treated samples, which makes them more susceptible to digestion. Autoclaving at 2.56atm, for 30min, produces a significant decrease of IgE-binding capacity of peanut allergens.


In vitro UV-B effect on lens protein solutions.
To investigate the effects of UV-B exposure on the protein solutions of different lens parts, rabbit lenses were separated into the equator (Eq), anterior cortex (Ac), nucleus (Nu) and posterior cortex (Pc). After homogenization, the water-soluble protein from each part was irradiated with UV-B at 0 to 0.225 J/cm2. Alterations in the content of protein SH, carbonyl groups, light scattering intensity and SDS-PAGE pattern were measured to compare the effect of UV-B on the protein solutions of various lens parts with or without additional GSH to test its preventive effect. The results showed that after UV-B irradiation, the protein sulfhydryl groups are gradually reduced. The nonprotein thiol (GSH added to the protein solution) was lost more rapidly than the protein sulfhydryl. The high molecular bands on the SDS-PAGE pattern mainly aggregated with disulfide. UV-B damage also increased the content of carbonyl groups and light scattering, irrespective of the lens parts. Lens proteins from the equator suffered the least damage while those of the nucleus were most strongly affected by UV-B exposure. This study suggests that the lens proteins from various lens parts have different responses to UV-B exposure; the sensitivity was in the following order: Eq < Ac < or = Pc < Nu.


L-phenylalanine:tRNA ligase of Escherichia coli K10. A rapid kinetic investigation of the catalytic reaction.
The kinetics of the amino acid activation and the transfer of the amino acid to tRNA have been investigated for L-phenylalanine:tRNA ligase of Escherichia coli K10 by stopped-flow and radioactive techniques. The rapid kinetics were followed by the observation of the displacement of the fluorescent dye, 6-p-toluidinylnaphthalene-2-sulfonate from the binding site of L-phenylalanine under conditions where a single active site of the enzyme was involved. The following results are of particular interest. (1) Equilibrium binding of L-phenylalanine and tRNAPhe indicates in each case two sites of interaction with an approximately tenfold difference of the binding affinity. (2) Experimental conditions of the kinetic investigation were chosen to favor reactions at the high affinity binding sites. Under those conditions, the rate constants have been evaluated at 1 mM magnesium to be in the range 12-25 sec-1 for the activation reaction and 42-77 sec-1 for the reverse, the variation of the values depending on those of the dissociation constants used for computation. The rate constant for the transfer reaction is 0.05 sec-1 and for the reverse 0.19 sec-1. The forward reaction is rate limiting for the overall reaction at single turnover and steady-state conditions. (3) All rate constants depend on the concentration of magnesium. Evidence is provided that the transfer occurs via a productive enzyme-tRNAPhe complex which is in a magnesium-dependent equilibrium with an unproductive complex, high magnesium favoring the former. The position of the tRNA-CCA end in the productive complex is such, that the fluorescent dye can be displaced by Phe-tRNAPhe. The thermodynamics of the overall reaction have been treated on the basis of the partial reactions. The free enthalpy of the completed reaction was calculated to be very close to zero. The significance of the adenylate intermediate is discussed with respect to the product inhibition expected on the basis of the tendency of tRNAPhe and L-phenylalanine to form tight complexes with the enzyme.


Functional Evidence of the Involvement of the Dynein Light Chain DYNLRB2 in Murine Leukemia Virus Infection.
How murine leukemia virus (MLV) travels from the cell membrane to the nucleus and the mechanism for nuclear entry of MLV DNA in dividing cells still remain unclear. It seems likely that the MLV preintegration complex (PIC) interacts with cellular proteins to perform these tasks. We recently published that the microtubule motor cytoplasmic dynein complex and its regulator proteins interact with the MLV PIC at early times of infection, suggesting a functional interaction between the incoming viral particles, the dynein complex, and dynein regulators. To better understand the role of the dynein complex in MLV infection, we performed short hairpin RNA (shRNA) screening of the dynein light chains on MLV infection. We found that silencing of a specific light chain of the cytoplasmic dynein complex, DYNLRB2, reduced the efficiency of infection by MLV reporter viruses without affecting HIV-1 infection. Furthermore, the overexpression of DYNLRB2 increased infection by MLV. We conclude that the DYNLRB2 light chain of the cytoplasmic dynein complex is an important and specific piece of the host machinery needed for MLV infection.IMPORTANCE Retroviruses must reach the chromatin of their host to integrate their viral DNA, but first they must get into the nucleus. The cytoplasm is a crowded environment in which simple diffusion is slow, and thus viruses utilize retrograde transport along the microtubule network, mediated by the dynein complex. Different viruses use different components of this multisubunit complex. We have found that murine leukemia virus (MLV) associates functionally and specifically with the dynein light chain DYNLRB2, which is required for infection. Our study provides more insight into the molecular requirements for retrograde transport of the MLV preintegration complex and demonstrates, for the first time, a role for DYNLRB2 in viral infection.


Involvement of human ribosomal proteins in nucleolar structure and p53-dependent nucleolar stress.
The nucleolus is a potent disease biomarker and a target in cancer therapy. Ribosome biogenesis is initiated in the nucleolus where most ribosomal (r-) proteins assemble onto precursor rRNAs. Here we systematically investigate how depletion of each of the 80 human r-proteins affects nucleolar structure, pre-rRNA processing, mature rRNA accumulation and p53 steady-state level. We developed an image-processing programme for qualitative and quantitative discrimination of normal from altered nucleolar morphology. Remarkably, we find that uL5 (formerly RPL11) and uL18 (RPL5) are the strongest contributors to nucleolar integrity. Together with the 5S rRNA, they form the late-assembling central protuberance on mature 60S subunits, and act as an Hdm2 trap and p53 stabilizer. Other major contributors to p53 homeostasis are also strictly late-assembling large subunit r-proteins essential to nucleolar structure. The identification of the r-proteins that specifically contribute to maintaining nucleolar structure and p53 steady-state level provides insights into fundamental aspects of cell and cancer biology.


Subversion of plasmacytoid and myeloid dendritic cell functions in chronic HCV infection.
Insufficient elimination of the hepatitis C virus (HCV) during acute infection results in chronic disease in the majority of patients due to weak virus-specific immune responses. Dendritic cells (DC) play a central role in recognition of HCV and in induction of innate and adaptive immune responses. In this study, we evaluated the frequency and functions of plasmacytoid dendritic cells (PDC) and myeloid dendritic cells (MDC) in patients with chronic HCV infection. We found that both the numbers and IFNalpha production capacity of blood PDC were significantly reduced in patients with chronic HCV infection compared to normal controls. While the frequency of MDC was not affected in chronic HCV, the allostimulatory capacity of monocyte-derived MDC was significantly decreased compared to normals. Lipopolysaccharide (LPS)-induced maturation improved the allostimulatory capacity of HCV infected patients' MDC that still remained significantly lower compared to normal controls. Our experiments revealed that MDC defects can be induced by HCV core and NS3 proteins suggesting virus-induced mechanisms for the DC defects in HCV infection. Finally, using toll-like receptor 2 (TLR2) and TLR4 deficient or mutant mice, we demonstrated that TLR2 but not TLR4 was critical in recognition of HCV core and NS3 proteins by innate immune cells. Further, TLR2 recognition of HCV core and NS3 was not augmented by co-expression of the TLR co-receptor, CD14. These data demonstrate that both PDC and MDC functions are impaired in patients with chronic HCV infection and DC defects are likely related to interaction of HCV viral products with innate immune cells.


Intra-operative mapping of cortical areas involved in reading in mono- and bilingual patients.
In order to identify the cortical areas involved in the reading process and to spare them during surgery, we systematically studied cortical areas by direct cortical stimulation in patients operated on for brain tumours. Seventy-six cortical stimulation mapping studies for language were performed in 35 monolingual and 19 bi- or multilingual patients over a 5-year period. We systematically searched for reading interference areas in addition to standard naming areas using an 'awake surgery' technique for brain mapping. A 'reading aloud' task (translated into different languages in multilingual patients) was used. Brain mapping was performed in left (44 patients) and right (10 patients) hemispheres. Cortical areas involved in reading were identified according to the type of interference, location and distinctness from naming areas. Stimulation of several major hemispheric regions resulted in significant interference with reading aloud: (i) the lower part of the pre- and postcentral gyri (P < 0.00001); (ii) the dominant supramarginal, angular and the posterior part of the superior temporal gyri (P < 0.00001); (iii) in the dominant inferior and middle frontal gyri (P < 0.001); and (iv) in the posterior part of the dominant middle temporal gyrus (P < 0.05). Interferences in reading were generally found in small cortical areas, with intervening areas evoking no reading interferences. Only partial overlap between reading and naming sites was found. Reading-specific sites were preferentially found when stimulating dominant inferior parietal or posterior temporal areas. Different types of reading interferences were noted. While 'articulatory' interferences were found in pre- and postcentral gyri bilaterally, and ocular-induced movements in bilateral middle frontal gyri, paraphasias were found mainly in the dominant supramarginal and posterior superior temporal gyri. Reading arrest sites were found in many regions. Reading interference sites were also occasionally found in the non-dominant hemisphere. In bilingual patients, if common cortical areas could be found, language- and reading-specific areas were sometimes detected, lending support to the concept that bilinguals can have relatively distinct cortical representation of their language skills. Finally, in this series, the location of reading interference sites and their relative specialization showed considerable individual variability.


Functional Compounds of Cold-Pressed Pomegranate Seed Oil: Fatty Acids and Phytosterols Profile as Quality Biomarkers for Origin Discrimination.
Cold-pressed pomegranate seed oil (PSO) is a product of the extraction of non-edible pomegranate seeds. Its unique chemical composition in terms of both polyunsaturated fatty acids, especially punicic acid (PA), and secondary metabolites, such as phytosterols, tocopherols and phenols, make it an interesting functional ingredient for food enrichment. It is not clear if the biomarkers profile of PSO depends to factors connected to the geographical origin of seeds. This work presents a statistical comparative analysis, concerning biomolecules composition and geographical origin of 32 commercial cold-pressed PSOs, performed by principal component analysis. The study discriminates between Turkish and Italian PSOs, on the base of the fatty acid profile and phytosterols, and not on the tocopherols and phenols. These results confirmed PA as the main characteristic biomarker of oil genuineness and, for the first time, disclosed a statistically relevant variability of phytosterols, which can be proposed as quality biomarkers for discrimination of geographical origins.


[An original revealing mode of sarcoidosis: Sweet's syndrome].
Sweet's syndrome is a neutrophilic dermatosis which usually presents as an idiopathic disorder. The combination of Sweet's syndrome and sarcoidosis is rare. We report the clinical case of a Sweet's syndrome revealing sarcoidosis.


Scabies of the nail unit.
Scabies limited to the nail unit is quite unusual, but may persist after treatment of crusted scabies. We present a man with a history of crusted scabies that resolved with treatment, but later the patient reported a chronic problem with crumbly, thickened nails, which were found to be harboring scabies mites.


Investigate the correlation between clinical sign and symptoms and the presence of P. gingivalis, T. denticola, and T. forsythia individually or as a "Red complex" by a multiplex PCR method.
The aim of this study was to investigate the correlation between endodontic clinical signs and symptoms and the presence of Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia or their association by Multiplex polymerase chain reaction assay. Microbial samples were taken from 30 cases with necrotic pulp tissues in primary infections. DNA was extracted from the samples, which were analyzed for the presence of three endodontic pathogens by using species-specific primers. P. gingivalis, T. denticola, T. forsythia, and Red Complex were present in 11, 17, 4, and 2 canals, respectively. Clinical and statistically significant relationships were found between T. forsythia and mobility and between T. denticola and swelling. (P < 0.05). Presence of other Red complex bacteria shows clinical association with presence of signs and symptoms but no statistically significant relationship. The high prevalence of P. gingivalis, T. denticola, and T. forsythia in the examined samples suggests that these bacteria are related to the etiology of symptomatic periradicular diseases.


Drosophila melanogaster as a model organism for bluetongue virus replication and tropism.
Bluetongue virus (BTV) is the etiological agent of bluetongue (BT), a hemorrhagic disease of ruminants that can cause high levels of morbidity and mortality. BTV is an arbovirus transmitted between its ruminant hosts by Culicoides biting midges (Diptera: Ceratopogonidae). Recently, Europe has experienced some of the largest BT outbreaks ever recorded, including areas with no known history of the disease, leading to unprecedented economic and animal welfare issues. The current lack of genomic resources and genetic tools for Culicoides restricts any detailed study of the mechanisms involved in the virus-insect interactions. In contrast, the genome of the fruit fly (Drosophila melanogaster) has been successfully sequenced, and it is used extensively as a model of molecular pathways due to the existence of powerful genetic technology. In this study, D. melanogaster is investigated as a model for the replication and tropism of BTV. Using reverse genetics, a modified BTV-1 that expresses the fluorescent mCherry protein fused to the viral nonstructural protein NS3 (BTV-1/NS3mCherry) was generated. We demonstrate that BTV-1/NS3mCherry is not only replication competent as it retains many characteristics of the wild-type virus but also replicates efficiently in D. melanogaster after removal of the bacterial endosymbiont Wolbachia pipientis by antibiotic treatment. Furthermore, confocal microscopy shows that the tissue tropism of BTV-1/NS3mCherry in D. melanogaster resembles that described previously for BTV in Culicoides. Overall, the data presented in this study demonstrate the feasibility of using D. melanogaster as a genetic model to investigate BTV-insect interactions that cannot be otherwise addressed in vector species.


[MUltiple sclerosis and obstetric epidural analgesia].
A prior diagnosis of multiple sclerosis (MS) has been considered a contraindication for performing epidural blocks due to the possible negative impact of the course of disease. For this reason, women with MS who given birth have rarely benefited from obstetric epidural analgesia. We report the case of a woman giving birth at full-term who had been diagnosed one year before the pregnancy of "probable" MS. She was given epidural analgesia with a mixture of bupivacaine and fentanyl at low doses. Both the birth and the immediate postpartum period transpired without complications and no new signs of disease were reported over the following years. We conclude that obstetric epidural analgesia with bupivacaine administered at a low concentration is safe for women with MS.


Coronary sinus stenosis: an underdiagnosed cause for paediatric exertional chest pain.
Undiagnosed coronary sinus obstruction can be a source of paediatric exertional chest pain and death. We present a case series of three interesting children who developed only exertional angina from various degrees of coronary sinus stenosis or atresia. We discuss the diagnosis and management of each case and the potential pathophysiology involved with their symptoms.


The RNA-binding protein DND1 acts sequentially as a negative regulator of pluripotency and a positive regulator of epigenetic modifiers required for germ cell reprogramming.
The adult spermatogonial stem cell population arises from pluripotent primordial germ cells (PGCs) that enter the fetal testis around embryonic day (E)10.5. PGCs undergo rapid mitotic proliferation, then enter prolonged cell cycle arrest (G1/G0), during which they transition to pro-spermatogonia. In mice homozygous for the Ter mutation in the RNA-binding protein Dnd1 (Dnd1Ter/Ter ), many male germ cells (MGCs) fail to enter G1/G0 and instead form teratomas: tumors containing many embryonic cell types. To investigate the origin of these tumors, we sequenced the MGC transcriptome in Dnd1Ter/Ter mutants at E12.5, E13.5 and E14.5, immediately prior to teratoma formation, and correlated this information with DO-RIP-Seq-identified DND1 direct targets. Consistent with previous results, we found DND1 controls downregulation of many genes associated with pluripotency and active cell cycle, including mTor, Hippo and Bmp/Nodal signaling pathway elements. However, DND1 targets also include genes associated with male differentiation, including a large group of chromatin regulators activated in wild-type but not mutant MGCs during the E13.5 and E14.5 transition. Results suggest multiple DND1 functions and link DND1 to initiation of epigenetic modifications in MGCs.


Insight Into the Long Noncoding RNA and mRNA Coexpression Profile in the Human Blood Transcriptome Upon Leishmania infantum Infection.
Visceral leishmaniasis (VL) is a vector-borne infectious disease that can be potentially fatal if left untreated. In Brazil, it is caused by Leishmania infantum parasites. Blood transcriptomics allows us to assess the molecular mechanisms involved in the immunopathological processes of several clinical conditions, namely, parasitic diseases. Here, we performed mRNA sequencing of peripheral blood from patients with visceral leishmaniasis during the active phase of the disease and six months after successful treatment, when the patients were considered clinically cured. To strengthen the study, the RNA-seq data analysis included two other non-diseased groups composed of healthy uninfected volunteers and asymptomatic individuals. We identified thousands of differentially expressed genes between VL patients and non-diseased groups. Overall, pathway analysis corroborated the importance of signaling involving interferons, chemokines, Toll-like receptors and the neutrophil response. Cellular deconvolution of gene expression profiles was able to discriminate cellular subtypes, highlighting the contribution of plasma cells and NK cells in the course of the disease. Beyond the biological processes involved in the immunopathology of VL revealed by the expression of protein coding genes (PCGs), we observed a significant participation of long noncoding RNAs (lncRNAs) in our blood transcriptome dataset. Genome-wide analysis of lncRNAs expression in VL has never been performed. lncRNAs have been considered key regulators of disease progression, mainly in cancers; however, their pattern regulation may also help to understand the complexity and heterogeneity of host immune responses elicited by L. infantum infections in humans. Among our findings, we identified lncRNAs such as IL21-AS1, MIR4435-2HG and LINC01501 and coexpressed lncRNA/mRNA pairs such as CA3-AS1/CA1, GASAL1/IFNG and LINC01127/IL1R1-IL1R2. Thus, for the first time, we present an integrated analysis of PCGs and lncRNAs by exploring the lncRNA-mRNA coexpression profile of VL to provide insights into the regulatory gene network involved in the development of this inflammatory and infectious disease.


Heparan sulfate proteoglycan of human colon: partial molecular cloning, cellular expression, and mapping of the gene (HSPG2) to the short arm of human chromosome 1.
We have determined the sequence of two overlapping cDNA clones encoding a portion of the human heparan sulfate proteoglycan core protein (HSPG2) from a human colon library. The cDNA clones encompassed 1.34 kb of nucleotide sequence and showed approximately 85% homology to the murine heparan sulfate proteoglycan of the EHS tumor, BPG-5. The deduced amino acid sequence revealed an identity of 87% between the human and the murine species. Of the 57 different amino acids encoded in the human clones, 20 were substituted with a similar amino acid. Among the specific features that were highly conserved was the 32 cysteine residues with a distinctive repeat pattern characteristic of epidermal growth factor. Northern blotting revealed a single, approximately 12 kb transcript in a variety of cells including human colon carcinoma, endothelial, and fibroblastic cells. The size of this transcript correlated with the estimated molecular weight (approximately 400 kDa) of the protein core precursor. Southern blot analyses of DNA from 120 human/rodent somatic cell hybrids, including subclones with specific translocations or spontaneous breaks of human chromosome 1, demonstrated the presence of HSPG2 gene on the telomeric region of the short arm of chromosome 1 (1p34-pter). Two polymorphisms with TaqI and EcoRI restriction endonucleases, respectively, were also detected. The localization of this proteoglycan locus in the human genome and the availability of new RFLPs provide the tools for future studies of human diseases where the HSPG2 proteoglycan gene is suspected to be involved.


Implementation of the "Pregnancy Reasonably Excluded Guide" for Pregnancy Assessment: A Quality Initiative in Outpatient Gynecologic Surgery.
Preoperative evaluation for pregnancy at our institution lacked standardization among individual health care providers and surgical services. This pilot project aimed to improve assessment for pregnancy before scheduled outpatient gynecologic surgical procedures. The Pregnancy Reasonably Excluded Guide incorporates historic, evidence-based criteria to facilitate identification of patients with a higher chance of pregnancy. We retrospectively reviewed documentation for women undergoing gynecologic surgery at an outpatient surgical center from March through September 2016, before and after implementation of the pregnancy assessment protocol. After implementation, all eligible women (aged 18-50 years, not undergoing an emergent or pregnancy-related procedure) were assessed using the Pregnancy Reasonably Excluded Guide on arrival to the preoperative area. The Pregnancy Reasonably Excluded Guide checklist uses traditional and World Health Organization criteria for reasonable exclusion of pregnancy. Nursing staff reviewed responses with patients and pregnancy tests were completed as indicated by patient responses. Women who were unable to read, understand, or freely respond to the checklist received pregnancy testing. Pregnancy assessment, testing, results, and delays were recorded. This project was deemed exempt by the institutional review board. Two hundred thirteen eligible patients underwent outpatient gynecologic procedures during the study period (excluding a 2-week washout period at implementation). In the preimplementation period, 93 of 136 patients (68%) had pregnancy risk documented; 73 of 77 (95%) had documentation in the postimplementation period (P≤.01). Pregnancy tests were completed in 45 preimplementation patients (33%) and 16 postimplementation patients (21%) (P=.06). No pregnancy test results were positive. No procedural delays were associated with pregnancy assessment. Patient-centered assessment using the Pregnancy Reasonably Excluded Guide at presentation for outpatient gynecologic surgery significantly improved evaluation and documentation of pregnancy status before scheduled procedures without increasing the number of pregnancy tests or causing procedural delays.


Silencing of IQGAP1 by shRNA inhibits the invasion of ovarian carcinoma HO-8910PM cells in vitro.
IQGAP1 is a scaffolding protein and overexpressed in many human tumors, including ovarian cancer. However, the contribution of IQGAP1 to invasive properties of ovarian cancer cells remains unknown. Here, we investigated the effect of IQGAP1-specific short hairpin RNA (shRNA) expressing plasmids on metastatic potential of ovarian cancer HO-8910PM cells. We used RT-PCR and Western blot analysis to characterize expression of IQGAP1 in three human ovarian cancer-derived cell lines SK-OV-3, HO-8910 and HO-8910PM. We then determined whether expression of endogenous IQGAP1 correlated with invasive and migratory ability by using an in vitro Matrigel assay and cell migration assay. We further knocked down IQGAP1 using shRNA expressing plasmids controlled by U1 promoter in HO-8910PM cells and examined the proliferation activity, invasive and migration potential of IQGAP1 shRNA transfectants using MTT assay, in vitro Matrigel-coated invasion assay and migration assay. IQGAP1 expression level seemed to be closely associated with the enhanced invasion and migration in ovarian cancer cell lines. Levels of both IQGAP1 mRNA and protein were significantly reduced in HO-8910PM cells transfected with plasmid-based IQGAP1-specific shRNAs. RNAi-mediated knockdown of IQGAP1 expression in HO-8910PM cells resulted in a significant decrease in cell invasion and migration. Our findings support the hypothesis that IQGAP1 promotes tumor progression and identify IQGAP1 as a potential therapeutic strategy for ovarian cancer and some other tumors with over-expression of the IQGAP1 gene.


Effects of seminal plasma on cooling-induced capacitative changes in boar sperm.
Porcine seminal plasma (SP) has been shown to contain factors that have a decapacitative or capacitation-inhibiting effect on sperm. The objectives of the present study were to compare the capacitative changes observed in cooled sperm with those seen in sperm after in vitro capacitation and to determine whether SP could prevent these changes. Sperm were subjected to incubation or to slow cooling under noncapacitating or capacitating conditions. The effect of SP on protein tyrosine phosphorylation and the ability of the sperm to undergo an acrosome reaction (AR) were determined. Cooled sperm displayed an increased level of tyrosine phosphorylation and a higher percentage of induced AR sperm compared to incubated sperm. The addition of SP inhibited the number of ARs that occurred during incubation and cooling. These results suggest that cooling of sperm augments the capacitative changes in sperm, and that SP contains a factor(s) that effectively prevents these changes.


Pathological features and prenatal diagnosis in the newly recognised limb/pelvis-hypoplasia/aplasia syndrome.
A second family with the autosomal recessive disorder now referred to as the limb/pelvis-hypoplasia/aplasia syndrome is reported. It is speculated that the gene for this rare skeletal dysplasia may be confined to the Middle East gene pool. The disorder has been shown to be diagnosable prenatally in a pregnancy at risk by using ultrasonography.


Exploring the impacts of ecosystem services on human well-being in Qinghai Province under the framework of the sustainable development goals.
Ecosystem services (ESs) play vital roles in meeting the needs of human well-being and supporting sustainable development. However, there is limited research on how the types, amounts, interactions, and changes of the ESs collectively impact human well-being under the context of sustainable development goals (SDGs) of the United Nations. This study selected Qinghai Province of China as the study area and intended to make such an attempt to fill this gap in terms of the following aspects: (1) analyzing the spatial patterns and changing trends of ten ESs (food supply, water supply, carbon sink, soil retention, sand fixation, hydrological regulation, flood mitigation,cultural service,net primary productivity, and habitat quality) in Qinghai Province from 2000 to 2018; (2)constructing a multi-level index system of human well-being under the framework of the SDGs, and setting the criteria to assess the level of local human well-being; and (3) building a structural equation model to explore the direct and indirect impacts of the types, amounts, interactions and changes of the ESs on actual human well-being and the gaps between actual and targeted human well-being. The findings revealed that: (1) most of the ecosystem services fluctuated with significant downward or upward trends during 2000-2018, except for four ESs (i.e., carbon sink, soil retention, flood mitigation, and habitat quality); (2) only a few indicators of local residents' well-being such as meat production, milk production, the numbers of medical technical personnel in hospitals and health centers, and the numbers of scientific and technical personnel met the SDG criteria in most time, while other indicators remained at low levels and there were large gaps between them and the SDG criteria; (3) actual human well-being and the gaps between actual and targeted human well-being were affected by the types, amounts, interactions and changes of the ESs with different degrees directly or indirectly. The approaches and results in this study are instructive for other regions of the world to make certain the roles of ESs in promoting human well-being and substantiating the SDGs.


Extrarenal aspects of angiotensin II function.
The cloning of angiotensin II (Ang II) receptor genes and the availability of specific receptor ligands allows characterization of Ang II receptor-mediated actions. Most of the well-known Ang II effects such as vasoconstriction, drinking response and cell proliferation are mediated through the AT1 receptor. Little is known about the physiological effect of the AT2 receptor, though there are some reports describing the involvement of the AT2 receptor in blood pressure regulation. Recent data demonstrate that the AT2-mediated actions are inhibitory to AT1- and mitogen-induced growth effects, indicating a balancing mechanism for Ang II-controlled mechanisms. It has also been demonstrated that AT2 receptor inactivation induces endothelial cell proliferation in the presence of Ang II. Additionally, AT2 receptor activation enhances nerve growth factor-induced differentiation of PCI2W cells and a role in apoptotic changes has also been reported. Based on recent findings, this article focuses on the role of Ang II in growth and differentiation processes with respect to the AT2 receptor in these events.


[Brain neuronal mechanisms of circadian rhythms in mammalians].
It is now widely accepted that the suprachiasmatic nucleus (SCN) of the hypothalamus is a circadian pacemaker in the mammalians. This conclusion is based on three principal lines of the following evidence. First, ablation of the SCN results in a loss of circadian rhythms in rodents. Second, the SCN exhibits rhythms in neuronal activity and glucose metabolism both in vivo and in vitro experiments. Third, the transplantation of fetal SCN to the third ventricle of animals rendered arrhythmic++ by SCN ablation restores circadian function. In this review the anatomical, physiological and pharmacological characteristics of SCN neurons in vitro are discussed by focusing especially upon the roles of various neurotransmitters and modulators in the circadian system of mammals, in relation to the function of SCN.


Corneal requirements for extended wear: an update.
The current status of extended wear is reviewed in terms of the ability of available rigid and soft contact lens materials to provide: oxygen to the cornea, lens movement, and resistance to deposit formation and corneal desiccation. Current hydrogel lenses seem unsuitable as a modality for extended wear due to limited oxygen transmissibility, except when the frequency of overnight wear is reduced. Rigid gas permeable lenses, while not without problems, show greater promise for extended wear at this time.


Obesity-associated digestive cancers: A review of mechanisms and interventions.
The prevalence of obesity has steadily increased over the past few decades. Previous studies suggest that obesity is an oncogenic factor and that over 20% of all cancers are obesity-related. Among such cancers, digestive system malignancies (including esophageal adenocarcinomas, colorectal cancers, and cancers of the gastric cardia, liver, and pancreas) are reported most frequently. While the 5-year survival rates of cancers of the breast and prostate are 90%, that rate is only 45% for digestive cancers. In this review, the mechanisms of obesity-associated digestive cancers are discussed, with an emphasis on obesity-related gene mutations, insulin and insulin-like growth factor signaling pathways, chronic inflammation, and altered adipokine levels. Evidence that these factors often function interdependently rather than independently in carcinogenesis is presented. Recommended interventions that may reduce the burden of obesity-associated digestive cancers, such as participation in physical activity, diet modulation, and calorie restriction, are also described.


Prevalence of valvular heart diseases and associated risk factors in Han, Uygur and Kazak population in Xinjiang, China.
Valvular heart diseases (VHD) is very common in clinical practice and has became the subject of growing attention in the field of cardiovascular medicine. Our aim was to assess the prevalence and correlates of VHD in the general population in Xinjiang, China. Using a 4-stage stratified cluster random sampling method, a total of 14618 participants were recruited in the Cardiovascular Risk Survey (CRS) study. The participants' personal information, medical history were assessed by questionnaire. VHD was diagnosed by transthoracic echocardiography. We carried out the statistical analysis utilizing SPSS Statistics version 19.0. In the total study group, VHD was observed in 1397 (9.65%) individuals. The prevalence rates of VHD in Han, Uygur and Kazak group are 13.51%, 2.71% and 12.29% respectively. The prevalence rates of VHD increased strikingly with age (all P < 0.001). The results of multinomial regression analysis indicated that VHD were related to age in Han group, to age smoking and hypertension in Uygur group, to age and hypertension in Kazak group. Our research provides a unique prevalence rate of VHD in Xinjiang natural population. The result suggests that VHD are notably common in this population (9.65%) and increase with age. There exists significant difference of prevalence rate between ethnics. The main risk factors of VHD are age, hypertension and smoking. Valvular heart diseases should be regarded as a serious and growing public-health problem.


Intertidal snail-trematode communities on the southern Thailand before and after the South Asia tsunami.
Intertidal snail-trematode communities in southern Thailand were examined before and after the South Asia tsunami. Infection rates and species diversity of cercaria in the host snail Cerithidea in tidal zones did not change significantly from one year before to one month after the tsunami. However, the host snails C. quadrata, C. alata and C. obtusa disappeared from greatly damaged sites. It is important to follow up on the intertidal snail-trematode community recovery process after destruction of the intertidal ecosystem.


Disruption of Osteoprotegerin has complex effects on medial destruction and adventitial fibrosis during mouse abdominal aortic aneurysm formation.
Aortic aneurysm refers to dilatation of the aorta due to loss of elasticity and degenerative weakening of its wall. A preventive role for osteoprotegerin (Opg) in the development of abdominal aortic aneurysm has been reported in the CaCl2-induced aneurysm model, whereas Opg was found to promote suprarenal aortic aneurysm in the AngII-induced ApoE knockout mouse aneurysm model. To determine whether there is a common underlying mechanism to explain the impact of Opg deficiency on the vascular structure of the two aneurysm models, we analyzed suprarenal aortic tissue of 6-month-old ApoE-/-Opg-/- mice after AngII infusion for 28 days. Less aortic dissection and aortic lumen dilatation, more adventitial thickening, and higher expression of collagen I and Trail were observed in ApoE-/-Opg-/- mice relative to ApoE-/-Opg+/+ mice. An accumulation of α-smooth muscle actin and vimentin double-positive myofibroblasts was noted in the thickened adventitia of ApoE-/-Opg-/- mice. Our results suggest that fibrotic remodeling of the aorta induced by myofibroblast accumulation might be an important pathological event which tends to limit AngII-induced aortic dilatation in ApoE -/-Opg-/- mice.


Targeted destruction of DNA replication protein Cdc6 by cell death pathways in mammals and yeast.
The highly conserved Cdc6 protein is required for initiation of eukaryotic DNA replication and, in yeast and Xenopus, for the coupling of DNA replication to mitosis. Herein, we show that human Cdc6 is rapidly destroyed by a p53-independent, proteasome-, and ubiquitin-dependent pathway during early stages of programmed cell death induced by the DNA-damaging drug adozelesin, or by a separate caspase-dependent pathway in cells undergoing apoptosis through an extrinsic pathway induced by tumor necrosis factor-alpha and cycloheximide. The proteasome-dependent pathway induced by adozelesin is conserved in the budding yeast Saccharomyces cerevisiae. The destruction of Cdc6 may be a primordial programmed death response that uncouples DNA replication from the cell division cycle, which is reinforced in metazoans by the evolution of caspases and p53.


Tobacco Smoking and Antisocial Deviance among Vietnamese, Vietnamese-American, and European-American Adolescents.
Tobacco smoking is one of the most significant modifiable behavioral health risk factors worldwide. Although smoking rates in some high-income countries (HIC) have declined, rates in many low-and-middle-income countries (LMIC) remain high. Adolescence is a key developmental risk period for smoking initiation. Research indicates that a major adolescent risk factor for tobacco smoking is antisocial deviance, which includes such behaviors as aggression, risk-taking, and rule-breaking. The linkages between antisocial deviance and smoking suggest that these behaviors and their underlying attitudes can be important targets for smoking prevention programs, but for public health efficiency it is important to target the components of antisocial deviance most closely linked smoking. However, although 80% of smokers live in LMIC, most relevant research has been conducted in HIC and its applicability to LMIC is unclear, given cultural differences between many HIC and LMIC. The purpose of the present study was to assess cross-cultural variations in relations among components of antisocial deviance and self-reported tobacco smoking among 2,724 10th and 11th grade Vietnamese, Vietnamese-American, and European-American students. Within the combined sample the relation between self-reported smoking and overall antisocial deviance was β = 0.33. However, the component of antisocial deviance most strongly related to smoking varied across groups, with Risk-taking most strongly related to smoking for Vietnamese-American (β = 0.37) and Vietnamese (β = 0.36) adolescents, and Rule-breaking Behavior most strongly related to smoking for European-American (β = 0.51) adolescents. These and other findings suggest the possible importance of culturally-tailored foci for smoking prevention programs emphasizing different aspects of antisocial deviance.


Effects of monocrotaline on endothelial nitric oxide synthase expression and sulfhydryl levels in rat lungs.
The nitric oxide-cyclic guanosine monophosphate signal-transduction mechanism plays a key role in the regulation of vascular tone and structure. Monocrotaline-induced pulmonary hypertension is associated with low bioavailability of nitric oxide. To characterize the mechanism(s) involved in this dysfunction, rats received a single subcutaneous injection of monocrotaline, normal saline (control), or monocrotaline plus daily L-arginine, a precursor of nitric oxide, in drinking water. Pulmonary artery pressure and right ventricular hypertrophy were assessed 2 weeks later. In addition, the authors evaluated the expression of endothelial nitric oxide synthase messenger RNA, endothelial nitric oxide synthase protein, cyclic guanosine monophosphate, and sulfhydryl levels in the lungs. Sulfhydryls are needed for the dynamic modulation of soluble guanylate cyclase by nitric oxide, which results in cyclic guanosine monophosphate formation. L-arginine treatment did not attenuate monocrotaline-induced pulmonary hypertension or right ventricular hypertrophy. Monocrotaline did not alter the expression of endothelial nitric oxide synthase messenger RNA or endothelial nitric oxide synthase protein in the lungs. Protein-bound sulfhydryls (28 +/- 5 vs. 75 +/- 16 pmol/microg protein) and cyclic guanosine monophosphate (0.63 +/- 0.05 vs. 1.06 +/- 0.017 pmol/microg protein) levels in the monocrotaline group were significantly low compared with controls. The low sulfhydryl levels, an indicator of oxidant stress, may account for the impaired availability of bioactive nitric oxide and low cyclic guanosine monophosphate levels. These results suggest that oxidative stress may, in part, contribute to the pathogenesis of pulmonary hypertension in the monocrotaline model.


[Total cavo-pulmonary anastomosis in the surgery of complicated congenital heart defects].
The authors discuss experience in 8 operations for total cavo-pulmonary anastomoses in patients with various complicated congenital heart anomalies in which radical or anatomical correction could not be undertaken. The operation for total cavo-pulmonary anastomosis is an alternative of Fonten's method since many authors claim that the last-named has some shortcomings. Total cavo-pulmonary anastomosis was established in 4 stages under conditions of extracorporeal circulation. End to side cavo-pulmonary anastomosis was formed in the first stage; the proximal end of the divided superior vena cava was joined to the pulmonary artery in the second stage; the communication between the heart and pulmonary artery was closed in the third stage, and, finally, a tunnel was formed between the inferior and superior venae cavae by means of a xenopericardial flap in the fourth stage. Six patients tolerated the operation successfully. The immediate postoperative period was more favourable than after Fonten's operation. However, to come to a deeper general conclusion and compare the two methods clinical material must be accumulated and the long-term results of the operations studied.


A single subunit from avian myeloblastosis virus with both RNA-directed DNA polymerase and ribonuclease H activity.
Two structurally distinct forms of RNA-directed DNA polymerase from avian myeloblastosis virus were resolved by chromatography on phosphocellulose and purified. In addition to RNA-directed DNA polymerase activity, both enzymes had ribonuclease H (RNase H) activity, which degraded the RNA moiety of RNA.DNA hybrids. As determined by sodium dodecyl sulfate-polyacrylamide disc-gel electrophoresis, one form had two subunits, alpha (alpha) and beta (beta), with molecular weights of 65,000 and 105,000, respectively. The other had a single subunit, alpha, with a molecular weight of 65,000. The sedimentation coefficients of alphabeta and alpha, determined by glycerol gradient centrifugation in 0.35 M KCl, were 7.8 S and 5.2 S, respectively. Both enzymes had similar antigenic determinants and could not be distinguished by a differential response to several different RNA and DNA templates. We suggest that alpha, which contains both RNA-directed DNA polymerase and RNase H activity, is derived by dissociation of alphabeta; the function of the beta subunit is unknown.


Mode conversion and separation in magneto-optical photonic crystal waveguide.
We present mode conversion in different magneto-optical photonic crystal (MOPC) waveguides. An odd-mode waveguide (OMW) and an even-mode waveguide (EMW) are designed by adjusting the geometric parameters of the waveguide. These waveguides are constructed by adding a layer of yttrium-iron-garnet (YIG) rods with opposing magnetic fields between an MOPC and an Al2O3 photonic crystal (PC). Due to the coupling effect caused by the middle layer of YIG rods, the OMW (or EMW) only supports an odd (or even) mode within a single-mode frequency range. Simulation results demonstrate that they can convert other modes into odd or even modes, and there is almost no power loss during the conversion. Most importantly, they are robust against backscattering from perfect electric conductors (PECs) and point defects. Based on these properties, we propose a device that can efficiently separate the odd and even modes into different ports. These results offer a novel approach to controlling the transmission modes of waveguides, which facilitates the interconnection of diverse topological magneto-optical waveguides.


Pooled data analysis of laparoscopic vs. open ventral hernia repair: 14 years of patient data accrual.
The purpose of this study was to analyze the published perioperative results and outcomes of laparoscopic (LVHR) and open (OVHR) ventral hernia repair focusing on complications and hernia recurrences. Data were compiled from all English-language reports of LVHR published from 1996 through January 2006. Series with fewer than 20 cases of LVHR, insufficient details of complications, or those part of a larger series were excluded. Data were derived from 31 reports of LVHR alone (unpaired studies) and 14 that directly compared LVHR to OVHR (paired studies). Chi-squared analysis, Fisher's exact test, and two-tailed t-test analysis were used. Forty-five published series were included, representing 5340 patients (4582 LVHR, 758 OVHR). In the pooled analysis (combined paired and unpaired studies), LVHR was associated with significantly fewer wound complications (3.8% vs. 16.8%, p < 0.0001), total complications (22.7% vs. 41.7%, p < 0.0001), hernia recurrences (4.3% vs. 12.1%, p < 0.0001), and a shorter length of stay (2.4 vs. 4.3 days, p = 0.0004). These outcomes maintained statistical significance when only the paired studies were analyzed. In the pooled analysis, LVHR was associated with fewer gastrointestinal (2.6% vs. 5.9%, p < 0.0001), pulmonary (0.6% vs. 1.7%, p = 0.0013), and miscellaneous (0.7% vs. 1.9%, p = 0.0011) complications, but a higher incidence of prolonged procedure site pain (1.96% vs. 0.92%, p = 0.0469); none of these outcomes was significant in the paired study analysis. No differences in cardiac, neurologic, septic, genitourinary, or thromboembolic complications were found. The mortality rate was 0.13% with LVHR and 0.26% with OVHR (p = NS). Trends toward larger hernia defects and larger mesh sizes were observed for LVHR. The published literature indicates fewer wound-related and overall complications and a lower rate of hernia recurrence for LVHR compared to OVHR. Further controlled trials are necessary to substantiate these findings and to assess the health care economic impact of this approach.


Highly differentiated projection-specific cortical subnetworks.
Pyramidal cells in the neocortex are differentiated into several subgroups based on their extracortical projection targets. However, little is known regarding the relative intracortical connectivity of pyramidal neurons specialized for these specific output channels. We used paired recordings and quantitative morphological analysis to reveal distinct synaptic transmission properties, connection patterns, and morphological differentiation correlated with heterogeneous thalamic input to two different groups of pyramidal cells residing in layer 5 (L5) of rat frontal cortex. Retrograde tracers were used to label two projection subtypes in L5: crossed-corticostriatal (CCS) cells projecting to both sides of the striatum, and corticopontine (CPn) cells projecting to the ipsilateral pons. Although CPn/CPn and CCS/CCS pairs had similar connection probabilities, CPn/CPn pairs exhibited greater reciprocal connectivity, stronger unitary synaptic transmission, and more facilitation of paired-pulse responses. These synaptic characteristics were strongly correlated to the projection subtype of the presynaptic neuron. CPn and CCS cells were further differentiated according to their somatic position (L5a and L5b, the latter denser thalamic afferent fibers) and their dendritic/axonal arborizations. Together, our data demonstrate that the pyramidal projection system is segregated into different output channels according to subcortical target and thalamic input, and that information flow within and between these channels is selectively organized.


Grandparent(s) coresidence and physical activity/screen time among Latino children in the United States.
Introduction: Latino Americans tend to have a familismo cultural value, in which grandparents often live with grandchildren and are involved in grandchildren rearing. The purpose of this study was to examine how grandparent(s) coresidence is associated with Latino American children's physical activity and screen time. Methods: This study used 2009-2010 Health Behavior in School-Aged Children (HBSC) Survey data that consisted of 2,608 Latino students from 5th to 10th grade. Associations between grandparent(s) coresidence and Latino children's physical activity/screen time were examined using logistic regression and generalized ordered logistic regression while controlling for children's sociodemographic variables, health-related variables, and family composition and relationship variables. Results: Grandparent(s) coresidence was associated with higher odds of being physically active for at least 60 min daily in the past 7 days but was not significantly associated with frequency/time of vigorous intensity physical activity. In addition, grandparent(s) coresidence was associated with higher odds of exceeding 2 hr of daily screen time during weekdays and weekend days. Discussion: Interventions aimed at promoting Latino children's physical activity should pay particular attention to use of screen-based media among children living with grandparents. In addition, it may be promising to involve Latino grandparents in promotion of Latino children's physical activity. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Haemodynamic performance of a new pericardial aortic bioprosthesis during exercise and recovery: comparison with pulmonary autograft, stentless aortic bioprosthesis and healthy control groups.
Since blood flow impairment by aortic valve prosthesis is characteristically dynamic, this dynamic component is best and thoroughly appreciated by exercise Doppler echocardiography. We sought to determine the haemodynamics of a new pericardial aortic bioprosthesis [Trifecta™-aortic valve bioprosthesis (T-AVB), St Jude Medical, MN, USA] at rest and during exercise and a 10-min recovery period in comparison with alternative aortic valve prostheses, e.g. Ross operation (RO), stentless aortic valve [Medtronic freestyle-aortic valve bioprosthesis (MF-AVB)] and a healthy control group (CO). Haemodynamics at rest and during supine exercise stress testing and a 10-min recovery period were evaluated in 32 patients (mean age: 70.8 ± 6.7 years) with T-AVB (mean follow-up: 5 ± 2 months), 49 with RO (mean age: 43.5 ± 13.7 years), 39 with an MF-AVB (mean age: 64.6 ± 9.4 years) and 26 healthy patients (mean age: 39 ± 9 years). Measurements included mean outflow tract gradient (δp mean, mmHg), effective orifice area index (EOAI, cm(2)/m(2)) and valvular resistance (vR, dyn s cm(-5)). Mean body surface area for T-AVB was 1.93 ± 0.24 m(2) (median 1.97 m(2)). Mean δp mean at rest was 7.2 ± 3.4 mmHg, mean EOAI 0.86 ± 0.23 cm(2)/m(2) and mean vR 50.7 ± 23.2 dyn s cm(-5). Supine stress testing did increase the mean EOAI to 0.98 ± 0.27 cm(2)/m(2), the mean vR to 62.6 ± 25.3 dyn s cm(-5) and the mean δp mean to 10.21 ± 4.7 mmHg, respectively (P < 0.05 for all comparisons). During the post-exercise recovery period, δp mean, EOAI and vR showed a prompt normalization within 5 min of cessation of exercise. At all the three measurement points, T-AVB and MF-AVB revealed low gradients, satisfactory EOAI and low vR. Compared with the RO and a healthy control group, both groups showed significantly inferior performance throughout the exercise and post-exercise study protocol (P < 0.05). In comparison with T-AVB, patients with an MF-AVB only showed significant inferior performance throughout series with respect to a higher vR, indicating a smaller increase in the EOAI during exercise. During the 10-min post-exercise period, T-AVB recovered significantly earlier than MF-AVB. When comparing two different types of aortic valve bioprostheses with a gold standard group (RO) and a healthy population, both aortic valve bioprostheses perform inferior but reveal promising haemodynamics during exercise. During post-exercise haemodynamic recovery, only the T-AVB revealed a nearly physiological recovery pattern compared with the RO and a healthy control group.


Reverberation of flexural waves scattered by a local heterogeneity in a plate.
A statistical model is proposed to relate the scattering properties of a local heterogeneity in a plate to the statistical properties of scattered and reverberated flexural waves. The contribution of the heterogeneity is isolated through the computation of differential signals consisting of a subtraction of the signals recorded after and before introduction of the heterogeneity. The theoretical expression of the average reverberation envelope of these differential signals is obtained as a function of the scattering cross-section of the heterogeneity. Successful numerical and experimental validations in various cases of canonical heterogeneities with known scattering cross-sections are shown. These satisfying results offer a way to estimate the scattering cross-section of an unknown scatterer from the reverberated differential signals.


Sepsis: Early Recognition and Optimized Treatment.
Sepsis is a life-threatening condition caused by infection and represents a substantial global health burden. Recent epidemiological studies showed that sepsis mortality rates have decreased, but that the incidence has continued to increase. Although a mortality benefit from early-goal directed therapy (EGDT) in patients with severe sepsis or septic shock was reported in 2001, three subsequent multicenter randomized studies showed no benefits of EGDT versus usual care. Nonetheless, the early administration of antibiotics and intravenous fluids is considered crucial for the treatment of sepsis. In 2016, new sepsis definitions (Sepsis-3) were issued, in which organ failure was emphasized and use of the terms "systemic inflammatory response syndrome" and "severe sepsis" was discouraged. However, early detection of sepsis with timely, appropriate interventions increases the likelihood of survival for patients with sepsis. Also, performance improvement programs have been associated with a significant increase in compliance with the sepsis bundles and a reduction in mortality. To improve sepsis management and reduce its burden, in 2017, the World Health Assembly and World Health Organization adopted a resolution that urged governments and healthcare workers to implement appropriate measures to address sepsis. Sepsis should be considered a medical emergency, and increasing the level of awareness of sepsis is essential.


Protective effects of ethynylestradiol on the hemodynamic changes induced by lipopolysaccharide in anesthetized rats.
Estrogen pretreatment has been reported to protect rats from death induced by endotoxin. We investigated the effects of posttreatment with a synthetic estrogen, ethynylestradiol, on arterial pressure and hemodynamics in thiobutabarbitone-anesthetized rats challenged with Escherichia coli lipopolysaccharide. Rats were i.v. injected with lipopolysaccharide (1 mg/kg) followed by vehicle or a single dose of ethynylestradiol (0.25, 0.5, or 1 mg/kg) 1 h later. Another group (time-matched control) was given the vehicle. In the time-control group, there was a slight decrease in mean arterial pressure (-10 +/- 3 mm Hg) but no significant changes in cardiac output, total peripheral resistance, or heart rate over the 6-h study period. Lipopolysaccharide progressively reduced mean arterial pressure and cardiac output (-27 +/- 8 mm Hg and -52 +/- 6 ml/min, after 6 h) and increased total peripheral resistance and heart rate (+0.33 +/- 0.10 mm Hg/min/ml and +21 +/- 13 beats/min, after 6 h). None of the time-control rats died, but 36% of the rats treated with lipopolysaccharide died between 3 and 6 h after endotoxin challenge. Ethynylestradiol, at 0.25 and 0.5 completely, and at 1 mg/kg partially, restored mean arterial pressure and cardiac output at 6 h after injection of lipopolysaccharide. Ethynylestradiol at 0.5 and 1 mg/kg, but not 0.25 mg/kg, completely reversed the increase in total peripheral resistance at 6 h after injection of lipopolysaccharide. Mortality was 14% in each of the three groups of rats given ethynylestradiol 1 h after lipopolysaccharide. Therefore posttreatment with ethynylestradiol attenuated hemodynamic changes in endotoxic shock.


Psychometric Tests for Hepatitis B - A Systematic Review.
Hepatitis B is a condition that directly affects hundreds of millions of people, who may require testing for certain psychological constructs. This systematic review presents the current state with regard to the instruments that are used for the measurement of psychological variables in relation to hepatitis B. We conducted a comprehensive search in bibliographic databases (PubMed, Embase, Scopus, Web of Science, PsycINFO, CINAHL, and the Cochrane Library), and grey literature search. We identified commonly used measures, their psychometric properties and gaps in the research. Our findings from the 38 papers included in the review indicate that while several tests have been developed to cater to hepatitis B patients, most are focused on quality of life, with few targeting other needed directions, such as stigma or attitudes to vaccination. We also show the limits in current measures and discuss potential improvements.


Five worthy finalists for our Patient's Choice award.
The RCNi Nurse Awards are not only the most prestigious accolades in nursing, they are also the only awards that give patients the opportunity to choose their own nurse of the year. This week we reveal the shortlist for the 2017 RCNi Patient's Choice award, and choosing between the final five will be as challenging as ever.


Draft Genome Sequence of Agrococcusbaldri Strain Marseille-P2731.
Agrococcus baldri strain Marseille-P2731 was isolated from a Siberian permafrost specimen dated around 10 million years. The 3,021,022-bp genome of strain Marseille-P2731, with a 71.82% G+C content, includes 2,844 protein-coding genes, 72 toxin/antitoxin modules, nine bacteriocin-encoding genes, and 1,266 genes associated with mobilome.


Bringing Micro to the Macro: How Citizen Science Data Enrich Geospatial Visualizations to Advance Health Equity.
Social and spatial contexts affect health, and understanding nuances of context is key to informing successful interventions for health equity. Layering mixed methods and mixed scale data sources to visualize patterns of health outcomes facilitates analysis of both broad trends and person-level experiences across time and space. We used micro-scale citizen scientist-collected data from four Bay Area communities along with aggregate epidemiologic and population-level data sets to illustrate barriers to, and facilitators of, physical activity in low-income aging adults. These data integrations highlight the synergistic value added by combining data sources, and what might be missed by relying on either a micro- or macro-level data source alone. Mixed methods and granularity data integration can generate a deeper understanding of environmental context, which in turn can inform more relevant and attainable community, advocacy, and policy improvements.


Measurement properties of instruments assessing permanent functional impairment of the spine: a systematic review protocol.
Permanent functional impairment (PFI) of the spine is a rating system used by compensation authorities, such as workers compensation boards, to establish an appropriate level of financial compensation for persistent loss of function. Determination of PFI of the spine is commonly based on the assessment of spinal movement combined with other measures of physical and functional impairments; however, the reliability and validity of the measurement instruments used for these evaluations have yet to be established. The aim of this study is to systematically review and synthesise the literature concerning measurement properties of the various and different instruments used for assessing PFI of the spine. Three conceptual groups of terms (1) PFI, (2) spinal disorder and (3) measurement properties will be combined to search Medline, EMBASE, CINAHL, Web of Science, Scopus, PEDro, OTSeeker and Health and Safety Science Abstracts. We will examine peer-reviewed, full-text articles over the full available date range. Two reviewers will independently screen citations (title, abstract and full text) and perform data extraction. Included studies will be appraised as to their methodological quality using the COnsensus-based Standards for the selection of health Measurement INstruments criteria. Findings will be summarised and presented descriptively, with meta-analysis pursued as appropriate. This review will summarise the current level of evidence of measurement properties of instruments used for assessing PFI of the spine. Findings of this review may be applicable to clinicians, policy-makers, workers' compensation boards, other insurers and health and safety organisations. The findings will likely provide a foundation and direction for future research priorities for assessing spinal PFI. CRD42017060390.


Stress distributions in peri-miniscrew areas from cylindrical and tapered miniscrews inserted at different angles.
The purpose of this study was to analyze stress distributions in the roots, periodontal ligaments (PDLs), and bones around cylindrical and tapered miniscrews inserted at different angles using a finite element analysis. We created a three-dimensional (3D) maxilla model of a dentition with extracted first premolars and used 2 types of miniscrews (tapered and cylindrical) with 1.45-mm diameters and 8-mm lengths. The miniscrews were inserted at 30°, 60°, and 90° angles with respect to the bone surface. A simulated horizontal orthodontic force of 2 N was applied to the miniscrew heads. Then, the stress distributions, magnitudes during miniscrew placement, and force applications were analyzed with a 3D finite element analysis. Stresses were primarily absorbed by cortical bone. Moreover, very little stress was transmitted to the roots, PDLs, and cancellous bone. During cylindrical miniscrew insertion, the maximum von Mises stress increased as insertion angle decreased. Tapered miniscrews exhibited greater maximum von Mises stress than cylindrical miniscrews. During force application, maximum von Mises stresses increased in both groups as insertion angles decreased. For both cylindrical and tapered miniscrew designs, placement as perpendicular to the bone surface as possible is recommended to reduce stress in the surrounding bone.