What are the Relevant Outcomes of the Periodic Health Examination? A Comparison of Citizens' and Experts' Ratings.
Despite evidence from clinical guideline development that physicians and patients show discordance in what they consider important in outcome selection and prioritization, it is unclear to what extent outcome preferences are concordant between experts and citizens when it comes to the context of primary prevention. Therefore, the objective of this study was to assess whether expert judgments about the importance of beneficial and harmful outcomes differ from citizen preferences when considering intervention options for a periodic health examination (PHE) program. We conducted an online survey using a modified Delphi approach. The target population for the survey consisted of citizens who had attended the PHE (n=18) and experts who made evidence-based recommendations (n=11). Citizens and experts assigned a score on a 9-point Likert scale for each outcome of 14 interventions. We analyzed the intragroup agreement based on Krippendorff's alpha and the intergroup agreement using the cube root product measure (CRPm). We further tested for significant differences between the groups using the Mann U-test. Agreements within the groups of citizens and experts varied across the interventions and tended to be poor (α ≤0 to 0.20) or fair (α = 0.21 to 0.40), with three exceptions showing moderate agreement (α = 0.44 to 0.55). The agreements between the citizens and experts across the interventions was fair (CRPm = 0.28) during the first Delphi rating round. The mean differences between the citizens and experts on the Likert scale ranged from 0.0 to 3.8 during the first rating round and from 0.0 to 3.3 during the second. Across interventions, the citizens rated the outcomes as more important than the experts did (p<0.01). Individual participants' ratings varied substantially. Because experts generally underestimated the outcomes' importance to citizens, the involvement of citizens in guideline panels for preventive services is important.


Can Vitex Agnus Castus be Used for the Treatment of Mastalgia? What is the Current Evidence?
There have been many treatments suggested for the management of mastalgia; one of these is the fruit extract of Vitex Agnus castus L. commonly known as Agnus castus, an extract of a deciduous shrub native to Mediterranean Europe and Central Asia. It is postulated that A. castus suppresses the stress-induced latent hyperprolactinemia which is a release of supra-physiological levels of prolactin in some patients in response to stressful stimuli. It is postulated that A. castus could be effective in the treatment of cyclical mastalgia by inhibiting the release of excess prolactin by blocking Dopamine-2 receptor type on pituitary. The adverse events following A. castus treatment are mild and reversible. The aim of this review is assess the efficacy of A. castus in the treatment of mastalgia. Data from randomized and non-randomized studies regarding the efficacy and safety of A. castus is reviewed in a systematic fashion. It is concluded that A. castus can be considered as an efficient alternative phytotherapeutic agent in the treatment of mastalgia.


Superiority of DAT over ELISA as a diagnostic and seroepidemiological tool for the diagnosis of Indian Kala-azar.
The aim of this study was to evaluate two methods for the diagnosis of Kala-azar. The sera of 160 individuals were evaluated by ELISA using soluble antigen and direct agglutination test (DAT) for Kala-azar. These were categorized as 100 cases of clinically and parasitologically confirmed Kala-azar and 60 controls. The controls included clinically suspected but parasitologically not confirmed Kala-azar patients (10), endemic normals (15), non-endemic normals (19), typhoid fever (10) and malaria (15). The positivity rate amongst the clinically and parasitologically confirmed Kala-azar patients by ELISA and DAT were 93% and 98% respectively. Out of 10 clinically suspected Kala-azar cases three showed positive reaction in ELISA and two in DAT. Of the endemic normals, one case was found positive by both the tests whereas ELISA was found positive in one additional case. DAT did not show any cross reactivity with malaria while ELISA was found positive in one case. Both endemic normals and typhoid fever cases showed no reaction by both tests. ELISA showed a sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 93%, 90%, 93% and 90% respectively while for DAT these values were 98%, 95%, 98 and 95% respectively. The diagnostic accuracy for ELISA and DAT was found to be 91.9% and 96.9%, respectively. The present study shows that DAT is a simple, sensitive, specific and cost effective test with high PPV and NPV along with approximately 97% diagnostic accuracy and is comparable to ELISA. It may be applied for the routine diagnosis as well as seroepidemiological study of Kala-azar.


Jiella pacifica sp. nov., isolated from the West Pacific Ocean.
A Gram-stain-negative bacterium, designated strain 40Bstr34T, isolated from a sediment sample from the West Pacific Ocean, was taxonomically characterized by using a polyphasic approach. The strain was phylogenetically close to Jiella aquimaris LZB041T and Jiella endophytica CBS5Q-3T, with 16S rRNA gene sequence similarities of 98.5 and 97.1 %, respectively. The genome of strain 40Bstr34T featured a G+C content of 65.7 % for a 5.8 Mb chromosome. Up-to-date bacterial core gene set analysis revealed that strain 40Bstr34T represents one independent lineage with J.aquimaris LZB041T. In silico DNA-DNA hybridization values between strain 40Bstr34T and its phylogenetic neighbours ranged from 30.3-34.2 %, below the cutoff of 70 %. In addition, the corresponding average nucleotide identity values were between 81.8-83.7 %, which are lower than 95 % threshold. The predominant cellular fatty acids of strain 40Bstr34T were summed feature 8 (C18 : 1 ω6c and/or C18 : 1 ω7c), cyclo-C19 : 0 ω8c and iso-C17 : 0 3-OH, and ubiquinone-10 as the predominant respiratory quinone. The major polar lipids included phosphatidylethanolamine, phosphatidylmonomethylethanolamine, diphosphatidylglycerol, phosphatidylglycerol, phosphatidylcholine, two unidentified aminolipids and two unidentified lipids. Based on the results of phenotypic, chemotaxonomic and genetic analyses, strain 40Bstr34T is identified as representing a novel species of the genus Jiella for which the name Jiella pacifica sp. nov. is proposed. The type strain is 40Bstr34T (=JCM 33903T=MCCC 1K04569T).


Sound strategy: acoustic aposematism in the bat-tiger moth arms race.
The night sky is the venue for an ancient arms race. Insectivorous bats with their ultrasonic sonar exert an enormous selective pressure on nocturnal insects. In response insects have evolved the ability to hear bat cries, to evade their hunting maneuvers, and some, the tiger moths (Arctiidae), to utter an ultrasonic reply. We here determine what it is that tiger moths "say" to bats. We chose four species of arctiid moths, Cycnia tenera, Euchaetes egle, Utetheisa ornatrix, and Apantesis nais, that naturally differ in their levels of unpalatability and their ability to produce sound. Moths were tethered and offered to free-flying naive big brown bats, Eptesicus fuscus. The ability of the bats to capture each species was compared to their ability to capture noctuid, geometrid, and wax moth controls over a learning period of 7 days. We repeated the experiment using the single arctiid species E. egle that through diet manipulation and simple surgery could be rendered palatable or unpalatable and sound producing or mute. We again compared the capture rates of these categories of E. egle to control moths. Using both novel learning approaches we have found that the bats only respond to the sounds of arctiids when they are paired with defensive chemistry. The sounds are in essence a warning to the bats that the moth is unpalatable-an aposematic signal.


Vemurafenib and BRAF inhibition: a new class of treatment for metastatic melanoma.
The U.S. Food and Drug Administration recently approved vemurafenib for the treatment of BRAF valine in exon 15, at codon 600 (V600E) mutant metastatic melanoma. Vemurafenib is a competitive small-molecule serine-threonine kinase inhibitor that functions by binding to the ATP-binding domain of mutant BRAF. Compared with dacarbazine chemotherapy, vemurafenib significantly improved the 6-month overall survival of patients from 64% to 84% and exhibited a response rate of approximately 50%. Median progression-free survival was also significantly improved with vemurafenib as compared with dacarbazine (5.3 versus 1.6 months, respectively), and this was consistent among groups analyzed, including age, sex, geography, Eastern Cooperative Oncology Group status, disease stage, and serum lactate dehydrogenase. The success of targeting melanoma genomics has created a paradigm shift for future drug development. Currently, the elucidation of resistant mechanisms to vemurafenib therapy remains an important area of active investigation that will shape rational drug treatments for melanoma. The development of vemurafenib, the role of BRAF targeting, and the changing landscape of treatment for melanoma provide a new foundation for clinical investigation.


Glass buildings on river banks as "polarized light traps" for mass-swarming polarotactic caddis flies.
The caddis flies Hydropsyche pellucidula emerge at dusk from the river Danube and swarm around trees and bushes on the river bank. We document here that these aquatic insects can also be attracted en masse to the vertical glass surfaces of buildings on the river bank. The individuals lured to dark, vertical glass panes land, copulate, and remain on the glass for hours. Many of them are trapped by the partly open, tiltable windows. In laboratory choice experiments, we showed that ovipositing H. pellucidula are attracted to highly and horizontally polarized light stimulating their ventral eye region and, thus, have positive polarotaxis. In the field, we documented that highly polarizing vertical black glass surfaces are significantly more attractive to both female and male H. pellucidula than weakly polarizing white ones. Using video polarimetry, we measured the reflection-polarization characteristics of vertical glass surfaces of buildings where caddis flies swarmed. We propose that after its emergence from the river, H. pellucidula is attracted to buildings by their dark silhouettes and the glass-reflected, horizontally polarized light. After sunset, this attraction may be strengthened by positive phototaxis elicited by the buildings' lights. The novelty of this visual-ecological phenomenon is that the attraction of caddis flies to vertical glass surfaces has not been expected because vertical glass panes do not resemble the horizontal surface of waters from which these insects emerge and to which they must return to oviposit.


Slaying the last unicorn: discovery of histones in the microalga Nanochlorum eucaryotum.
Histones are the principal constituents of eukaryotic chromatin. The four core histones (H2A, H2B, H3 and H4) are conserved across sequenced eukaryotic genomes and therefore thought to be universal to eukaryotes. In the early 1980s, however, a series of biochemical investigations failed to find evidence for histones or nucleosomal structures in the microscopic green alga Nanochlorum eucaryotum. If true, derived histone loss in this lineage would constitute an exceptional case that might help us further understand the principles governing eukaryotic gene regulation. To substantiate these earlier reports of histone loss in N. eucaryotum, we sequenced, assembled and quantified its transcriptome. Following a systematic search for histone-fold domains in the assembled transcriptome, we detect orthologues to all four core histones. We also find histone mRNAs to be highly expressed, comparable to the situation in other eukaryotes. Finally, we obtain characteristic protection patterns when N. eucaryotum chromatin is subjected to micrococcal nuclease digestion, indicating widespread formation of nucleosomal complexes in vivo. We conclude that previous reports of missing histones in N. eucaryotum were mistaken. By all indications, Nanochlorum eucaryotum has histone-based chromatin characteristic of most eukaryotes.


Muscarinic receptor regulation of chronic pain-induced atrial fibrillation.
Atrial fibrillation (AF), one of the most common arrhythmias, is associated with chronic emotional disorder. Chronic pain represents a psychological instability condition related to cardiovascular diseases, but the mechanistic linkage connecting chronic pain to AF occurrence remains unknown. Wild-type C57BL/6J male mice were randomly divided into sham and chronic pain groups. Autonomic nerve remodeling was reflected by the increased atrial parasympathetic tension and muscarinic acetylcholine receptor M2 expression. AF susceptibility was assessed through transesophageal burst stimulation in combination with electrocardiogram recording and investigating AERP in Langendorff perfused hearts. Our results demonstrated the elevated protein expression of muscarinic acetylcholine receptor M2 in the atria of mice subjected to chronic pain stress. Moreover, chronic pain induced the increase of atrial PR interval, and atrial effective refractory periods as compared to the sham group, underlying the enhanced susceptibility of AF. Thus, autonomic cholinergic nerve may mediate mice AF in the setting of chronic pain.


Predictors of breast and cervical cancer screening in a Spanish metropolitan area.
Gynecological cancers are an important cause of morbidity and mortality. Screening with mammography and Pap smear reduces breast and cervical cancer mortality. Neverthless, high participation rates are needed to ensure their effectiveness. We sought to assess the use of mammography and Pap smear and analyzed predictors of attendance at these cancer screenings in a large metropolitan area in Spain. We included women surveyed in the Madrid City Health Survey 2005. Cancer screening included mammography in the last 2 years and Pap smear in the last 3 years. Independent variables included sociodemographics, chronic diseases, and lifestyles. Predictors of mammography or Pap smear attendance were explored using logistic regression. The number of women eligible for mammography, aged >or=40 years, was 2580, and the number eligible for Pap smear, aged 18-69 years, was 3200. Overall, 60.5% and 76.6%, respectively, had received a mammography and Pap smear. Mammography uptake was positively associated with age, higher educational level, and osteomuscular disease. Obesity and unhealthy lifestyle were associated with nonattendance to mammography. Predictors of Pap smear attendance were the same as for mammography. Attendance at gynecological cancer screening in a large metropolitan area in Spain is acceptable in the age group for which it is recommended. An effort must be made, however, to recruit those women who are less likely to undergo screening, as they are at the highest risk of having these diseases.


Diagnostic utility of IMP3 expression in thyroid neoplasms: a quantitative RT-PCR study.
The capability of molecular markers to differentiate between benign and malignant well-differentiated thyroid tumors remains unclear. The aim of this study was to evaluate the use of insulin-like growth factor II mRNA binding protein-3 (IMP3) mRNA expression to distinguish benign from malignant thyroid tumors. RNA samples from 80 formalin-fixed, paraffin-embedded thyroid tissues, including 22 usual papillary thyroid carcinomas (PTCs), 18 follicular variants of PTC, 5 follicular thyroid carcinomas, 33 follicular adenomas, and 2 hyperplastic nodules, were used for quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis. IMP3 mRNA expression levels in thyroid tumors were expressed as relative fold change (fold) after normalization with normal thyroid RNA. The results showed that thyroid carcinomas including PTC, follicular variants of PTC, and follicular thyroid carcinomas have significantly higher IMP3 expression levels with 48.3, 35.3, and 43.8 fold, respectively, compared with benign thyroid lesions (2.8 fold). Using the IMP3 expression value of 5 fold as a cutoff point to separate benign and malignant thyroid tumors, IMP3 qRT-PCR analysis had a 91.4% clinical specificity and 86.7% clinical sensitivity for the diagnosis of well-differentiated thyroid carcinomas. Conventional RT-PCR and immunohistochemical analysis for IMP3 in a subset of cases supported the qRT-PCR results. These results indicate that detection of IMP3 mRNA expression levels by qRT-PCR may be a useful molecular marker to assist in the diagnosis of well-differentiated thyroid carcinomas.


Physical conditioning of less fit adults by use of leg weight loading.
Physical conditioning using weighted ankle spats was evaluated in eight men in the age range 33 to 45 years (mean, 38.4). Evaluation consisted of pretraining and posttraining heart rate (HR) and oxygen uptake (VO2) responses to five submaximal work loads: cycling six minutes at 600 kilopond meter per minute (kpm/min); level walking for ten minutes at both 4.0 and 5.6 km/hr with and without a 1.5-kg weight spat added to each ankle. After the initial baseline evaluation, subjects wore 1.5-kg weight spats on both ankles for three weeks and were reevaluated; during the next three-week period weight was increased to 2.25 kg per ankle. Following the six-week evaluation period, subjects did not wear ankle spats, and detraining was evaluated after three weeks. A control group of four subjects was evaluated at these same submaximal work loads on three different occasions with three-week periods between evaluations. The experimental group wore the spats about 13.5 hours per day and averaged 6.85 km/day (4.25 miles per day) during training. After six weeks of training, submaximal HR decreased 6 to 9 beats per minute (P smaller than 0.05) from pretraining values for all five submaximal work loads; predicted VO2 max and predicted work capacity to achieve a HR of 170 beats per minute increased by approximately 10%. Detraining submaximal HR responses increased slightly, but not significantly, from post six-week training responses. Control group submaximal responses were unchanged between evaluations. It was concluded that individuals who initially possess a low level of cardiorespiratory fitness may have a low threshold for training. Thus, leg weight conditioning may be extremely useful for rehabilitation of patients and for sedentary middle-aged men as special adaptation prio to more high intensity training.


Bioinformatics Analysis and RNA-Sequencing of SCAMP3 Expression and Correlated Gene Regulation in Hepatocellular Carcinoma.
Secretory Carrier Membrane Proteins 3 (SCAMP3) is a transmembrane protein that affects intracellular trafficking, protein sorting and vesicle formation. Overexpression of SCAMP3 correlates with poorly differentiated hepatocellular carcinoma (HCC). However, the expression and corresponding gene regulation of SCAMP3 in HCC remain unclear. Bioinformatics analyses of clinical parameters and survival data were conducted to predict the prognostic value of SCAMP3 in HCC. RNA sequencing and real-time PCR were conducted to confirm the SCAMP3 expression in HCC tissue. Expression was analyzed using OncomineTM and UALCAN, while SCAMP3 alterations and survival analysis were identified by cBioPortal. Differential gene expression with SCAMP3 was analyzed by LinkedOmics and GEPIA. The target networks of enzymes and co-transcriptional factors were identified using Gene enrichment analysis. Expression of SCAMP3 in HCC tissue was detected by RNA-sequencing and Western-blotting. Based on bioinformatics analysis and detection of mRNA expression, SCAMP3 was over-expressed in numerous tumors, especially in HCC. SCAMP3 level was positively correlated with disease stages and tumor grades and negatively correlated with patient survival. Furthermore, functional network analysis indicated that SCAMP3 regulated metabolic process and DNA replication through oxidative phosphorylation and chromatin remodeling or Ribosome. SCAMP3 regulated a number of gene expressions including PPAP2B, SNRK, ARID4A, PRCC, VPS72 via protein binding and proteasome, which may affect cell adhesion, proliferation, transcription, cell cycle and metabolism. Further, Real-time PCR and Western-blotting showed that the SCAMP3 level was increased in HCC tissue. The present data analysis efficiently reveals information about SCAMP3 expression and correlated function in HCC, laying a foundation for further study of SCAMP3 in the tumor.


Maternal dietary lipids alter bone chemical composition, mechanical properties, and histological characteristics of progeny of Japanese quail.
This study evaluated the effects of maternal dietary lipids on chemical components and mechanical and histological properties of tibia in progeny of Japanese quail fed different dietary lipids. Laying hens were fed a basal diet containing either soybean oil (SBO), hydrogenated soybean oil (HSBO), chicken fat (CF), or menhaden fish oil (FO) at 50 g/kg of the diet. The various maternal dietary lipid treatments did not affect growth of progeny at any developmental stage. There were no differences in tibial length, diameter, or collagen content. Tibial percentage ash was significantly higher in newly hatched progeny from hens fed the FO and HSBO diets. The levels of tibial deoxypyridinoline and total pyridinium crosslinks were higher in the FO and HSBO groups at hatch. At 7 d of age, the tibial deoxypyridinoline links remained higher in the FO group compared to the CF and SBO groups. Likewise, progeny from hens consuming the FO or HSBO diet had higher tibial shear force and stiffness at 7 and 14 d of age. There were no pronounced differences in tibial fracture energy and deflection among treatments. Maternal FO or HSBO enlarged the cartilaginous proliferative and hypertrophic zones of the tibial proximal end in newly hatched quail, which was accompanied by a thicker cortical bone in the diaphysis. However, the width of the hypertrophic zones tended to be smaller in these two groups coupled with improvement in trabecular density and cortical thickness in the proximal end and cortical density in the diaphysis at 3 wk of age. These results suggest that maternal dietary lipids altered bone development by influencing organic matrix quality and mineralization in embryos.


Synthesis of trifluoromethylaryl diazirine and benzophenone derivatives of etomidate that are potent general anesthetics and effective photolabels for probing sites on ligand-gated ion channels.
To locate the binding sites of general anesthetics on ligand-gated ion channels, two derivatives of the intravenous general anesthetic etomidate (2-ethyl 1-(phenylethyl)-1H-imidazole-5-carboxylate), in which the 2-ethyl group has been replaced by photoactivable groups based on either aryl diazirine or benzophenone chemistry, have been synthesized and characterized pharmacologically. TDBzl-etomidate (4-[3-(trifluoromethyl)-3H-diazirin-3-yl]benzyl 1-(1-phenylethyl)-1H-imidazole-5-carboxylate) and BzBzl-etomidate (4-benzoylbenzyl-1-(1-phenylethyl)-1H-imidazole-5-carboxylate are both potent general anesthetics with half-effective anesthetic concentrations of 700 and 220 nM, respectively. Both agents resembled etomidate in enhancing currents elicited by low concentrations of GABA on heterologously expressed GABAA receptors and in shifting the GABA concentration-response curve to lower concentrations. They also allosterically enhanced the binding of flunitrazepam to mammalian brain GABAA receptors. Both agents were also effective and selective photolabels, photoincorporating into some, but not all, subunits of the Torpedo nicotinic acetylcholine receptor to a degree that was allosterically regulated by an agonist or a noncompetitive inhibitor. Thus, they have the necessary pharmacological and photochemical properties to be useful in identifying the site of etomidate-induced anesthesia.


Database management in family medicine.
A computerized database will serve a practice well if physicians and staff make their expectations and needs explicit, establish clear database specifications, and use those specifications as the basis for selecting appropriate data management software and computer hardware. Any computerized database management system introduced into a practice should be thoroughly documented, and the process of implementing the system should be planned in advance. Finally, because a practice's information-related needs, expectations, and capabilities change over time, database usage should be reviewed and refined regularly.


Comparison of the preventive analgesic effect of rectal ketamine and rectal acetaminophen after pediatric tonsillectomy.
There is a little data about rectal administration of Ketamine as a postoperative analgesic, so we compared the efficacy of rectal ketamine with rectal acetaminophen, which is applied routinely for analgesia after painful surgeries like tonsillectomy. In this single-blinded comparative trial, we enrolled 70 children undergoing elective tonsillectomy, and divided them randomly in two groups. Patients received rectal ketamine (2 mg / kg) or rectal acetaminophen (20 mg / kg) at the end of surgery. The children's Hospital of Eastern Ontario Pain scale was used to estimate pain in children. Also the vital signs, Wilson sedation scale, and side effects in each group were noted and compared for 24 hours. The ketamine group had a lower pain score at 15 minutes and 60 minutes after surgery in Recovery (6.4 ± 0.8, 7.4 ± 1 vs. 7.1 ± 1.2, 7.8 ± 1.2 in the acetaminophen group, P < 0.05) and one hour and two hours in the ward (7.2 ± 0.7, 7 ± 0.5 vs. 7.9 ± 1.2, 7.5 ± 1.2 in the acetaminophen group, P < 0.05), with no significant differences till 24 hours. Dreams and hallucinations were not reported in the ketamine group. Systolic blood pressure was seen to be higher in the ketamine group (104.4 ± 7.9 vs. 99.8 ± 7.7 in the acetaminophen group) and nystagmus was reported only in the ketamine group (14.2%). Other side effects were equivalent in both the groups. With low complications, rectal ketamine has analgesic effects, especially in the first hours after surgery in comparison with acetaminophen, and it can be an alternative analgesic with easy administration in children after tonsillectomy.


Effect of temperature on growth, hemagglutination, and protease activity of Porphyromonas gingivalis.
Bacteria persisting in periodontal pockets are exposed to elevated temperatures during periods of inflammation. Temperature is an environmental factor that can modulate gene expression. Consequently, in the present study we examined the effect of temperature on the expression of virulence determinants by the periodontopathogen, Porphyromonas gingivalis. P. gingivalis W50 was grown in a complex medium under hemin excess at pH 7.0 and at a constant temperature of either 37, 39, or 41 degrees C; cultures were monitored for protease and hemagglutinin activity. P. gingivalis grew well at all three temperatures. An increase in growth temperature from 37 to 39 degrees C resulted in a 65% reduction in both total arginine- and lysine-specific activities (P < 0.01). A further rise in growth temperature to 41 degrees C led to even greater reductions in arginine-specific (82%; P < 0.001) and lysine-specific (73%; P < 0. 01) activities. These reductions were also associated with an altered distribution of individual arginine-specific enzyme isoforms. At 41 degrees C, there was a disproportionate reduction in the level of the heterodimeric RI protease, which also contains adhesin domains. The reduction also correlated with a markedly diminished hemagglutination activity of cells, especially in those grown at 41 degrees C, and a reduced immunoreactivity with a monoclonal antibody which recognizes gene products involved in hemagglutination. Thus, as the environmental temperature increased, P. gingivalis adopted a less aggressive phenotype, while retaining cell population levels. The coordinate down-regulation of virulence gene expression in response to an environmental cue linked to the intensity of the host inflammatory response is consistent with the clinically observed cyclical nature of disease progression in periodontal diseases.


EPIC-1042 as a potent PTRF/Cavin1-Caveolin-1 interaction inhibitor to induce PARP1 autophagic degradation and suppress temozolomide efflux for Glioblastoma.
Temozolomide (TMZ) treatment efficacy in glioblastoma is determined by various mechanisms such as TMZ efflux, autophagy, base excision repair (BER) pathway, and the level of O 6-methylguanine-DNA methyltransferase (MGMT). Here, we reported a novel small-molecular inhibitor (SMI) EPIC-1042 (C20H28N6) with the potential to decrease TMZ efflux and promote PARP1 degradation via autolysosomes in the early stage. EPIC-1042 was obtained from Receptor-based virtual screening. Co-immunoprecipitation and pull-down assays were applied to verify the blocking effect of EPIC-1042. Western blotting, Co-immunoprecipitation and immunofluorescence were used to elucidate the underlying mechanisms of EPIC-1042. In vivo experiments were performed to verify the efficacy of EPIC-1042 in sensitizing glioblastoma cells to TMZ. EPIC-1042 physically interrupted the interaction of PTRF/Cavin1 and caveolin-1, leading to reduced secretion of small extracellular vesicles (sEVs) to decrease TMZ efflux. It also induced PARP1 autophagic degradation via increased p62 expression that more p62 bound to PARP1 and specially promoted PARP1 translocation into autolysosomes for degradation in the early stage. Moreover, EPIC-1042 inhibited autophagy flux at last. The application of EPIC-1042 enhanced TMZ efficacy in glioblastoma in vivo. EPIC-1042 reinforced the effect of TMZ by preventing TMZ efflux, inducing PARP1 degradation via autolysosomes to perturb the BER pathway and recruitment of MGMT, and inhibiting autophagy flux in the later stage. Therefore, this study provided a novel therapeutic strategy using the combination of TMZ with EPIC-1042 for glioblastoma treatment.


Tetralogy of Fallot: controversies in early management.
Management of the cyanotic neonate with tetralogy of Fallot (ToF) remains a challenging condition. Outcomes for single-stage repair of ToF have steadily improved over the past 30 years and the best results have been achieved with repair between 3 and 9 months of age. The traditional management of cyanotic neonates and small infants has been palliation with a Blalock-Taussig shunt, but this continues to carry a significant mortality that has remained relatively constant even in the contemporary series. This has led to the promotion of neonatal complete repair, but analysis of published outcomes would suggest that this also carries significant risk compared to repair at an older age. Low birth weight and small pulmonary arteries (PAs) remain the greatest independent risk factors. Right ventricular outflow tract (RVOT) stenting may offer an alternative approach to neonatal repair in high-risk neonates and allow for PA growth and delay of repair until the child reaches a safer age. A stratified approach to early management utilizing RVOT stenting in high-risk cases may lead to better overall outcomes.


Dual-Energy CT: Balance Between Iodine Attenuation and Artifact Reduction for the Evaluation of Head and Neck Cancer.
Dual-energy computed tomography high energy virtual monochromatic images (VMIs) can reduce artifact but suppress iodine attenuation in enhancing tumor. We investigated this trade-off to identify VMI(s) that strike the best balance between iodine detection and artifact reduction. The study was performed using an Alderson radiation therapy phantom. Different iodine solutions (based on estimated tumor iodine content in situ using dual-energy computed tomography material decomposition) and different dental fillings were investigated. Spectral attenuation curves and quality index (QI: 1/SD) were evaluated. The relationship between iodine attenuation and QI depends on artifact severity and iodine concentration. For low to average concentration solutions degraded by mild to moderate artifact, the iodine attenuation and QI curves crossed at 95 keV. High energy VMIs less than 100 keV can achieve modest artifact reduction while preserving sufficient iodine attenuation and could represent a useful additional reconstruction for evaluation of head and neck cancer.


Pathway-Dependent Effectiveness of Network Algorithms for Gene Prioritization.
A network-based approach has proven useful for the identification of novel genes associated with complex phenotypes, including human diseases. Because network-based gene prioritization algorithms are based on propagating information of known phenotype-associated genes through networks, the pathway structure of each phenotype might significantly affect the effectiveness of algorithms. We systematically compared two popular network algorithms with distinct mechanisms--direct neighborhood which propagates information to only direct network neighbors, and network diffusion which diffuses information throughout the entire network--in prioritization of genes for worm and human phenotypes. Previous studies reported that network diffusion generally outperforms direct neighborhood for human diseases. Although prioritization power is generally measured for all ranked genes, only the top candidates are significant for subsequent functional analysis. We found that high prioritizing power of a network algorithm for all genes cannot guarantee successful prioritization of top ranked candidates for a given phenotype. Indeed, the majority of the phenotypes that were more efficiently prioritized by network diffusion showed higher prioritizing power for top candidates by direct neighborhood. We also found that connectivity among pathway genes for each phenotype largely determines which network algorithm is more effective, suggesting that the network algorithm used for each phenotype should be chosen with consideration of pathway gene connectivity.


The role of thrombomodulin in modulating ITGB3 expression and its implications for triple-negative breast cancer progression.
Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer (BC) compared to other BC subtypes in clinical settings. Currently, there are no effective therapeutic strategies for TNBC treatment. Therefore, there is an urgent need to identify suitable biomarkers or therapeutic targets for TNBC patients. Thrombomodulin (TM) plays a role in cancer progression and metastasis in many different cancers. However, the role of TM in TNBC is not yet fully understood. First, silenced-TM in MDA-MB-231 cells caused an increase in proliferative and metastatic activity. In contrast, overexpression of TM in Hs578T cells caused a reduction in proliferation, invasion, and migration rate. Using RNA-seq analysis, we found that Integrin beta 3 (ITGB3) expression may be a downstream target of TM. Furthermore, we found an increase in ITGB3 levels in TM-KD cells by QPCR and western blot analysis but a decrease in ITGB3 levels in TM-overexpressing cells. We found phospho-smad2/3 levels were increased in TM-KD cells but decreased in TM-overexpressing cells. This implies that TM negatively regulates ITGB3 levels through the activation of the smad2/3 pathway. Silencing ITGB3 in TM-KD cells caused a decrease in proliferation and migration. Finally, we found that higher ITGB3 levels were correlated with poor overall survival and relapse-free survival in patients with TNBC. Our results indicated a novel regulatory relationship between TM and ITGB3 in TNBC.


Improving delivery of care through change management.
This article describes an evidence-based care initiative and programme of clinical change which set out to improve the delivery of nursing care and related health outcomes for mentally disordered offender patients at Rampton Hospital. The programme has implications for all nursing specialties with studies also validated in mainstream psychiatric and general nursing contexts.


Characterization of a novel broad-spectrum antifungal protein from virus-infected Helminthosporium (Cochliobolus) victoriae.
A broad-spectrum anti-fungal protein of approximately 10 kDa, designated victoriocin, was purified from culture filtrates of a virus-infected isolate of the plant-pathogenic fungus Helminthosporium victoriae (teleomorph: Cochliobolus victoriae) by a multistep procedure involving ultrafiltration and reverse-phase high-performance liquid chromatography (RP-HPLC). Amino acid sequences, obtained by automated Edman degradation sequencing of RP-HPLC-purified victoriocin-derived peptides, were used to design primers for degenerate oligonucleotide-primed polymerase chain reaction (DOP-PCR) amplification from H. victoriae DNA and cDNA templates. An open reading frame coding for a victoriocin precursor of 183 amino acids with calculated molecular mass of approximately 20 kDa was amplified by PCR from H. victoriae genomic DNA but not from the control fungus Penicillium chrysogenum. Southern hybridization analysis confirmed the presence of the victoriocin gene in all H. victoriae strains tested. Sequence analysis indicated that victoriocin has a sequence motif similar to that found in scorpion short toxin/charybdotoxin and a consensus sequence similar to that found in defensins. Victoriocin, like some other antifungal proteins, including the totivirus-encoded killer proteins, is predicted to be expressed in vivo as a preprotoxin precursor consisting of a hydrophobic N-terminal secretion signal followed by a pro-region and terminating in a classical Kex2p endopeptidase cleavage site that generates the N terminus of the mature victoriocin. A putative cell wall protein of approximately 30 kDa (P30) co-purified with victoriocin from cultural filtrates. The potential role of P30 in the antifungal activity of H. victoriae culture filtrates is discussed.


Effect of body temperature on the cyclic fatigue resistance of the nickel-titanium endodontic instruments: A systematic review and meta-analysis of in vitro studies.
The aim of this systematic review was to compare the effect of body temperature (I) on the cyclic fatigue resistance (O) of nickel-titanium (NiTi) endodontic instruments (P) to that of room temperature (C). The study was registered in the PROSPERO database (CRD42020204286). A systematic search in PubMed, Scopus, Web of Science, Google Scholar, and OpenGrey was conducted in English until December 31, 2021. In vitro studies comparing the cyclic fatigue resistance of NiTi instruments at the body (35°C ± 2°C) and room temperature (20°C-25°C) were included. Eligible studies were evaluated for risk of bias and meta-analyzed to estimate the effects. Twenty-one studies out of 347 met the criteria for inclusion. The meta-analysis included six studies (n = 215) with comparative study parameters. The overall effect sizes (5.49; 95% confidence interval [CI]: 4.04-6.93) were significantly different (P < 0.001), indicating that the mean values at room temperature were significantly (P < 0.001) higher. The effect sizes for full rotary motion (standardized mean difference [SMD]: 4.80; 95% CI: 3.04-6.56) and reciprocating motion (SMD: 6.37; 95% CI: 3.63-9.11) were not significantly different (P = 0.346). Heterogeneity was high (I 2 = 94%). Sensitivity analysis revealed that the SMD values were not significantly different (P > 0.05) from the overall effect size, indicating that none of the studies had an effect on the overall effect size. Within the limitation of the study, the cyclic fatigue resistance of heat-treated NiTi endodontic files is significantly reduced at body temperature when compared to room temperature. Cyclic fatigue testing should be conducted at simulated body temperature.


Relaxometry of insensitive nuclei: optimizing dissolution dynamic nuclear polarization.
We report measurements of spin-lattice relaxation of carbon-13 as a function of the magnetic field ('relaxometry') in view of optimizing dissolution-DNP. The sample is temporarily lifted into the stray field above a high-resolution magnet using a simple and inexpensive 'shuttle'. The signals of arbitrary molecules can be observed at high field with high-resolution and sensitivity. During the dissolution process and subsequent 'voyage' from the polarizer to the NMR magnet, relaxation is accelerated by paramagnetic polarizing agents, but it can be quenched by using scavengers.


[Effect of estradiol on 3',5'-AMP-phosphodiesterase activity in rat uterus. Participation of hormone receptors, the role of guanyl nucleotides].
Estradiol (10(-7)-2 . 10(-5)M) is shown to inhibit the activity of phosphodiesterase of the soluble fraction of the mature rat womb tissue and to have no effect on the activity of adenylate cyclase of this tissue membrane fraction and on the phosphodiesterase of the tissue of the brain, heart and outer segments of the rod-cell. When blocking the estradiol cytosol receptors by clomiphene there is no inhibitory effect of the hormone on the activity of phosphodiesterase of the womb tissue preparations. Specific binding of estradiol by the cytosol receptors increases in the presence of guanylic nucleotides (10(-5)-10(-4)M); ATP does not affect this process. In the presence of guanyl-5-ilimidodiphosphate (Gpp(NH)p), a nonhydrolyzed analog of GTP, clomiphene does not block receptor binding of estradiol. ATP and GTP (10(-6)-10(-5)M), contrary to Gpp (NH)p, inhibit the phosphodiesterase activity. Independent of their effect on the enzymic activity, all the studied nucleotides partially or completely eliminate the inhibitory effect of estradiol on phosphodiesterase.


Studies of intercellular invasion in vitro using rabbit peritoneal neutrophil granulocytes (PMNS). I. Role of contact inhibition of locomotion.
Intercellular invasion is the active migration of cells on one type into the interiors of tissues composed of cells of dissimilar cell types. Contact paralysis of locomotion is the cessation of forward extension of the pseudopods of a cell as a result of its collision with another cell. One hypothesis to account for intercellular invasion proposes that a necessary condition for a cell type to be invasive to a given host tissue is that it lack contact paralysis of locomotion during collision with cells of that host tissue. The hypothesis has been tested using rabbit peritoneal neutrophil granulocytes (PMNs) as the invasive cell type and chick embryo fibroblasts as the host tissue. In organ culture, PMNs rapidly invade aggregates of fibroblasts. The behavior of the pseudopods of PMNs during collision with fibroblasts was analyzed for contact paralysis by a study of time-lapse films of cells in mixed monolayer culture. In monolayer culture, PMNs show little sign of paralysis of the pseudopods upon collision with fibroblasts and thus conform in their behavior to that predicted by the hypothesis.


Anti-arthritic activity of ethanolic extract of Tridax procumbens (Linn.) in Sprague Dawley rats.
To determine the anti-arthritic effect of whole plant ethanolic extract of Tridax procumbens (Asteraceae) in female Sprague Dawley (SD) rats using the Freund's Complete Adjuvant (FCA) model. The plant was collected from different regions of Madurai District, Tamil Nadu, and the phytoconstituents were identified through chemical tests. Ethanol (95%) was used to obtain the whole plant extraction through Soxhlet extractor. Female SD rats were used for anti-arthritic screening. Arthritis was induced using FCA, and the anti-arthritic effect of the ethanolic extract of T. procumbens was studied at doses of 250 and 500 mg/kg. The effects were compared with those of indomethacin (10 mg/kg). At the end of the study, the liver enzyme levels were determined and a radiological examination was carried out. The preliminary phytochemical analysis of the ethanolic extract of T. procumbens indicated the presence of alkaloids, tannins, flavonoids and saponins. T. procumbens at 250 and 500 mg/kg significantly inhibited the FCA-induced arthritis in the rats. This was manifested by as a decrease in the paw volume. The arthritic control animals exhibited a significant decrease in body weight compared with control animals without arthritis. T. procumbens animals showed dose dependent reduction in decrees in body weight and arthritis. At the same time, T. procumbens significantly altered the biochemical and haematological changes induced by FCA (P < 0.05). The anti-arthritic effect of T. procumbens was comparable with that of indomethacin. The whole plant extract of T. procumbens showed significant anti-arthritic activity against FCA-induced arthritis in female SD rats.


HIV infection, HAART, and endothelial adhesion molecules: current perspectives.
In this review we summarise the data on the effects of HIV infection and its therapy with antiretroviral drugs on adhesion molecules, considered to be potential biomarkers of endothelial cell function. This is a recent area of interest, given the unexpected associations between antiretroviral therapy, metabolic alterations of lipid profile, and the risk of cardiovascular disease in the absence of clear pathogenetic links. Although convincing prospective data are still scarce, it seems timely to elucidate the potential value of non-invasive, inexpensive tests for predicting cardiovascular risk in HIV-infected patients undergoing highly active antiretroviral therapy (HAART). Endothelial function, the most plausible link between infection, inflammation, and atherosclerosis, has been investigated since the beginning of the HIV epidemic. Increased concentrations of soluble adhesion molecules, such as those from the selectin and immunoglobulin families, have consistently been reported in HIV-positive patients. The introduction of HAART has renewed interest in the study of endothelial function in HIV-positive patients, in view of some HAART-related metabolic abnormalities (hyperlipidaemia, hyperglycaemia, fat redistribution) and several large reports of premature coronary artery disease. Whether HAART reduces endothelial injury associated with HIV infection or contributes to further endothelial cell activation is still a matter of controversy. Also unclear is whether HAART acts directly or indirectly, and if protease inhibitors and other classes of antiretroviral drugs differ in their proatherosclerotic effects. This article attempts to define the state of these emerging issues, identifies areas of controversy and of potential clinical relevance, and suggests some directions for future research.


[Ouabain induces Rho-dependent rock activation and membrane blebbing incultured endothelial cells].
Small G protein Rho and its most studied effectors, ROCK I and ROCK II, are involved in several cellular fuctions including smooth muscle and non-muscle cell contractions, cell migration and apoptosis. Activation of ROCK I by caspase-3 and activation of ROCK II by granzyme B are essential for membrane blebbing in the execution phase of apoptosis. In contrast, it has been demonstrated that Rho signaling is critical for blebbing developed after serum removal. As it was shown by us previously, ouabain induces membrane blebbing and proteolitic cleavage of ROCK I and ROCK II via caspases in human umbilical endothelial cells. However, caspase inhibitors do not prevent ouabain-induced blebs. Ouabain induces concentration-dependent cell death and membrane blebbing in endothelial cells. The aim of this study was to identify the possible role of Rho in ouabain-induced membrane blebbing. Pretreatment of endothelial cells with a Rho inhibitor CT04 did not inhibit the ouabain-induced cell death but prevented the development ofbleb formation. These results indicate that bleb formation is dependent on Rho activity in ouabain-induced cell death in HUVECs. Taken together, these results suggest that the mechanism of membrane bleb formation might be different depending on cell type and cell death-stimuli.


Complications preceding early deaths in Black and White children with acute myeloid leukemia.
Black patients have a twofold increased risk of induction mortality compared to White patients with acute myeloid leukemia (AML). We reviewed diagnosis and billing data from Pediatric Health Information System for 28 AML Induction I deaths to investigate conditions preceding death in White and Black patients. Half of deaths occurred within 10 days of initial diagnostic admission. Respiratory, cardiac, renal, and infectious complications were common prior to both White and Black deaths. Deaths in White patients were more commonly preceded by intracranial hemorrhage compared to deaths in Black patients. Future studies should assess management approaches of complications by race to identify modifiable processes that reduce mortality.


Klammt's Elastic Open Activator: Ricketts' cephalometrics results.
The purpose of this study is to investigate the orthodontic and orthopaedic real effects of the Klammt's Elastic Open Activator (EOA) in 25 Class II Division 1 patients in growing period. We wanted to determine statistically the cephalometrics changes produced in the patients, comparing the lateral cranium teleradiographies we took for the diagnosis with the ones we took at the end of treatment. At the end of this study we confirm that by using the EOA we obtained the desired effects, especially reducing the molar relation 2.53 mm and the overjet 2.56 mm. The EOA corrected the inclination and protrusion of incisors, although we cannot avoid the use of fixed appliances to round off. The reduction of 2.48 mm of facial convexity stands out as the most important skeletal effect; the facial depth angle increases 0.8 degree, and the maxillary depth decreases 1.16 degrees. The length of the mandibular corpus also increases 6.7 mm, although this change is mainly due to the growth of the patient. The changes in the aesthetic profile do not stand out.


The ideal guidance imaging system for endovascular interventions.
Endovascular interventions enable a minimally invasive approach to a variety of cardiovascular lesions. Small catheter-based delivery systems have rapidly evolved, diversifying endovascular therapeutic options. Coronary and peripheral vascular occlusive lesions may be amenable to angioplasty dilatation, intravascular stenting and ablation with mechanical atherectomy devices or lasers. New experimental transluminally placed endovascular stented grafts (TPEGs) have demonstrated feasibility for treating aneurysmal arteries, arteriovenous fistulas, and atherosclerotic occlusions. Improvements in imaging systems have provided better resolution of lesions, have improved patient selection and interventional strategy, and are invaluable for precise performance of procedures. The ideal guidance system should provide realtime imaging by a combination of complimentary modalities. These include cinefluoroscopy and contrast angiography, catheter-based intravascular ultrasound and angioscopy.


Quantitative predictions for DNA two-dimensional display according to size and nucleotide sequence composition.
2-D DNA display is a simple separation method that provides a fast and economical way of visualizing polymorphism and comparing genomes. The DNA fragments are separated first according to their size by standard gel electrophoresis and then according to their sequence composition using denaturing gradient gel electrophoresis. First developed by Fischer and Lerman (Cell 1979, 16, 191-200), this method has recently been used to distinguish strains within a bacterial species. The genomic restriction fragments are displayed as spots on a 2-D surface. Although most of the relevant physical mechanisms are understood, this technique is mostly empirical and remains essentially qualitative. In view of optimizing this procedure, we combine our understanding of the different physical mechanisms at play to develop a complete numerical model to predict the relative coordinates of the spots as a function of the corresponding DNA sequence and of the experimental conditions. We experimentally validate our model by predicting the outcome of a 2-D display of the lambda phage genome. It thus becomes possible to optimize in silico the experimental parameters, to predict whether specific mutations as well as yet undescribed genetic polymorphisms can be resolved, and to assist in interpreting the experimental data.


Role of a LORELEI- like gene from Phaseolus vulgaris during a mutualistic interaction with Rhizobium tropici.
Reactive oxygen species (ROS), produced by NADPH oxidases known as RBOHs in plants, play a key role in plant development, biotic and abiotic stress responses, hormone signaling, and reproduction. Among the subfamily of receptor-like kinases referred to as CrRLK, there is FERONIA (FER), a regulator of RBOHs, and FER requires a GPI-modified membrane protein produced by LORELEI (LRE) or LORELEI-like proteins (LLG) to reach the plasma membrane and generate ROS. In Arabidopsis, AtLLG1 is involved in interactions with microbes as AtLLG1 interacts with the flagellin receptor (FLS2) to trigger the innate immune response, but the role of LLGs in mutualistic interactions has not been examined. In this study, two Phaseolus vulgaris LLG genes were identified, PvLLG2 that was expressed in floral tissue and PvLLG1 that was expressed in vegetative tissue. Transcripts of PvLLG1 increased during rhizobial nodule formation peaking during the early period of well-developed nodules. Also, P. vulgaris roots expressing pPvLLG1:GFP-GUS showed that this promoter was highly active during rhizobium infections, and very similar to the subcellular localization using a construct pLLG1::PvLLG1-Neon. Compared to control plants, PvLLG1 silenced plants had less superoxide (O2-) at the root tip and elongation zone, spotty hydrogen peroxide (H2O2) in the elongation root zone, and significantly reduced root hair length, nodule number and nitrogen fixation. Unlike control plants, PvLLG1 overexpressing plants showed superoxide beyond the nodule meristem, and significantly increased nodule number and nodule diameter. PvLLG1 appears to play a key role during this mutualistic interaction, possibly due to the regulation of the production and distribution of ROS in roots.


Cortical thickness in symptomatic and asymptomatic bipolar offspring.
Children of parents diagnosed with bipolar disorder are at greater risk for developing a variety of psychiatric disorders, however, the reasons remain unknown. The present study aimed to investigate gray matter integrity in high-risk bipolar offspring (HRO) and healthy offspring (HCO) using cortical thickness techniques. Here we examined healthy control offspring (HCO; n=20) and HRO with (n=17) or without (n=13) psychiatric symptoms. T1-weighted images were collected from all offspring, and cortical thickness and age-cortical thickness correlations were compared. HRO showed cortical thinning in superior and inferior temporal regions, supramarginal, and caudal and rostral middle frontal regions compared to HCO. When comparing HRO with and without psychiatric symptoms, we found cortical thinning in symptomatic offspring in the superior frontal and somatosensory related cortices. Age-thickness correlations showed a relatively consistent negative relationship in most regions in HCO, while the reverse was true for the HRO. These regions included parahippocampal, lateral orbitofrontal, and inferior temporal regions. Our study provides evidence of cortical thickness reductions among symptomatic and asymptomatic high-risk offspring during youth. Some of these alterations, found in regions of emotion processing and regulation, are evident only when associated with the presence of psychiatric symptoms.


Improving the Design of a Conservation Reserve for a Critically Endangered Species.
Setting aside protected areas is a key strategy for tackling biodiversity loss. Reserve effectiveness depends on the extent to which protected areas capture both known occurrences and areas likely to support the species. We assessed the effectiveness of the existing reserve network for Leadbeater's Possum (Gymnobelideus leadbeateri) and other forest-dependent species, and compared the existing reserve system to a set of plausible reserve expansion options based on area targets implied in a recent Population Viability Analysis (PVA). The existing Leadbeater's Reserve and surrounding reserve system captured 7.6% and 29.6% of cumulative habitat suitability, respectively, across the landscape. Expanded reserve scenarios captured 34% to 62% of cumulative habitat suitability. We found acute trade-offs between conserving Leadbeater's Possum habitat and conserving habitat of other forest-dependent species. Our analysis provides a template for systematically expanding and evaluating reserve expansion options in terms of trade-offs between priority species' needs.


An experimental test of stationary lay-up periods and simulated transit on biofouling accumulation and transfer on ships.
Biofouling accumulation on ships' submerged surfaces typically occurs during stationary periods that render surfaces more susceptible to colonization than when underway. As a result, stationary periods longer than typical port residence times (hours to days), often referred to as lay-ups, can have deleterious effects on hull maintenance strategies, which aim to minimize biofouling impacts on ship operations and the likelihood of invasive species transfers. This experimental study tested the effects of different lay-up durations on the magnitude of biofouling, before and after exposure to flow, using fouling panels with three coating treatments (antifouling, foul-release, and controls), at two sites, and a portable field flume to simulate voyage sheer forces. Control panels subjected to extended stationary durations (28-, 45- and 60-days) had significantly higher biofouling cover and there was a 13- to 25-fold difference in biofouling accumulation between 10-days and 28-days of static immersion. Prior to flume exposure, the antifouling coating prevented biofouling accumulation almost entirely at one site and kept it below 20% at the other. Foul-release coatings also proved effective, especially after flume exposure, which reduced biofouling at one site from >52% to <6% cover (on average). The experimental approach was beneficial for co-locating panel deployments and flume processing using a consistent (standardized) flow regime on large panels across sites of differing conditions and biofouling assemblages. While lay-ups of commercial vessels are relatively common, inevitable, and unavoidable, it is important to develop a better understanding of the magnitude of their effects on biofouling of ships' submerged surfaces and to develop workable post-lay-up approaches to manage and respond to elevated biofouling accumulation that may result.


The conflicting effects of maternal nutrient restriction and early-life obesity on renal health.
Epidemiological and animal studies have demonstrated that early-life nutrition alters the metabolic responses and generates structural changes in complex tissues, such as the kidneys, which may lead to a reduction in the offspring lifespan. Independently, obesity induces a spontaneous low-grade chronic inflammatory response by modulating several of the major metabolic pathways that ultimately compromise long-term renal health. However, the combined effects of maternal nutrition and early-life obesity in the development of renal diseases are far from conclusive. Previous results, using the ovine model, demonstrated that the combination of a reduction in fetal nutrition and juvenile obesity induced a series of adaptations associated with severe metabolic syndrome in the heart and adipose tissue. Surprisingly, exposure to an obesogenic environment in the kidney of those offspring produced an apparent reduction in glomerulosclerosis in relation to age- and weight-matched controls. However, this reduction in cellular apoptosis was accompanied by a rise in glomerular filtration rate and blood pressure of equal intensity when compared with obese controls. The intention of this review is to explain the adaptive responses observed in this model, based on insights into the mechanism of renal fetal programming, and their potential interactions with some of the metabolic changes produced by obesity.


Diagnostic Accuracy of Multiparametric Magnetic Resonance Imaging to Identify Clear Cell Renal Cell Carcinoma in cT1a Renal Masses.
The detection of small renal masses is increasing with the use of cross-sectional imaging, although many incidental lesions have negligible metastatic potential. Among malignant masses clear cell renal cell carcinoma is the most prevalent and aggressive subtype. A method to identify such histology would aid in risk stratification. Our goal was to evaluate a likelihood scale for multiparametric magnetic resonance imaging in the diagnosis of clear cell histology. We retrospectively reviewed the records of patients with cT1a masses who underwent magnetic resonance imaging and partial or radical nephrectomy from December 2011 to July 2015. Seven radiologists with different levels of experience who were blinded to final pathology findings independently reviewed studies based on a predefined algorithm. They applied a clear cell likelihood score, including 1-definitely not, 2-probably not, 3-equivocal, 4-probably and 5-definitely. Binary classification was used to determine the accuracy of clear cell vs all other histologies. Interobserver agreement was calculated with the weighted κ statistic. A total of 110 patients with 121 masses were identified. Mean tumor size was 2.4 cm and 50% of the lesions were clear cell. Defining clear cell as scores of 4 or greater demonstrated 78% sensitivity and 80% specificity while scores of 3 or greater showed 95% sensitivity and 58% specificity. Interobserver agreement was moderate to good with a mean κ of 0.53. A clear cell likelihood score used with magnetic resonance imaging can reasonably identify clear cell histology in small renal masses and may decrease the number of diagnostic renal mass biopsies. Standardization of imaging protocols and reporting criteria is needed to improve interobserver reliability.


Phthalocyanines and porphyrinoid analogues as hole- and electron-transporting materials for perovskite solar cells.
Organic-inorganic lead halide perovskite absorbers in combination with electron and hole transporting selective contacts result in power conversion efficiencies of over 23% under AM 1.5 sun conditions. The advantage of perovskite solar cells is their simple fabrication through solution-processing methods either in n-i-p or p-i-n configurations. Using TiO2 or SnO2 as an electron transporting layer, a compositionally engineered perovskite as an absorber layer, and Spiro-OMeTAD as a HTM, several groups have reported over 20% efficiency. Though perovskite solar cells reached comparable efficiency to that of crystalline silicon ones, their stability remains a bottleneck for commercialization partly due to the use of doped Spiro-OMeTAD. Several organic and inorganic hole transporting materials have been explored to increase the stability and power conversion efficiency of perovskite solar cells. IIn this review, we analyse the stability and efficiency of perovskite solar cells incorporating phthalocyanine and porphyrin macrocycles as hole- and electron transporting materials. The π-π stacking orientation of these macrocycles on the perovskite surface is important in facilitating a vertical charge transport, resulting in high power conversion efficiency.


Gli3Xt-J/Xt-J mice exhibit lambdoid suture craniosynostosis which results from altered osteoprogenitor proliferation and differentiation.
Gli3 is a zinc-finger transcription factor whose activity is dependent on the level of hedgehog (Hh) ligand. Hh signaling has key roles during endochondral ossification; however, its role in intramembranous ossification is still unclear. In this study, we show that Gli3 performs a dual role in regulating both osteoprogenitor proliferation and osteoblast differentiation during intramembranous ossification. We discovered that Gli3Xt-J/Xt-J mice, which represent a Gli3-null allele, exhibit craniosynostosis of the lambdoid sutures and that this is accompanied by increased osteoprogenitor proliferation and differentiation. These cellular changes are preceded by ectopic expression of the Hh receptor Patched1 and reduced expression of the transcription factor Twist1 in the sutural mesenchyme. Twist1 is known to delay osteogenesis by binding to and inhibiting the transcription factor Runx2. We found that Runx2 expression in the lambdoid suture was altered in a pattern complimentary to that of Twist1. We therefore propose that loss of Gli3 results in a Twist1-, Runx2-dependent expansion of the sutural osteoprogenitor population as well as enhanced osteoblastic differentiation which results in a bony bridge forming between the parietal and interparietal bones. We show that FGF2 will induce Twist1, normalize osteoprogenitor proliferation and differentiation and rescue the lambdoid suture synostosis in Gli3Xt-J/Xt-J mice. Taken together, we define a novel role for Gli3 in osteoblast development; we describe the first mouse model of lambdoid suture craniosynostosis and show how craniosynostosis can be rescued in this model.


Low molecular weight heparin may benefit nephrotic remission in steroid‑sensitive nephrotic syndrome via inhibiting elastase.
Low molecular weight heparin (LMWH) has a structure similar to heparan sulfate, which exerts anti‑inflammatory effects via inhibiting elastase (Ela) activity. Release of Ela along the glomerular capillary wall may induce glomerular injury and proteinuria. The present study aimed to investigate the influence of LMWH on steroid‑sensitive nephrotic syndrome (SSNS) and the potential underlying mechanism. A total of 40 SSNS patients and 20 healthy controls were recruited. SSNS patients were treated with LMWH and prednisone simultaneously (LMWH+pred group) or with prednisone alone (pred group). Proteinuria, urinary glycosaminoglycans (GAGs), serum Ela and urinary creatinine levels were measured. The nephrotic period of SSNS was 15.93±5.78 days. The nephrotic period of SSNS in LMWH+pred group was significantly reduced compared with the pred group (14.13±4.56 vs. 18.63±6.49 days; P<0.05). At the follow‑up of the SSNS patients, there was no statistically significant difference in number of relapses between the LMWH+pred and pred groups. Proteinuria (2.51±0.97 g/24 h), urinary GAG levels (4.92±0.87 mg/mmol creatinine) and serum Ela levels (77.64±10.99 ng/l) were significantly greater in the nephrotic period of SSNS compared with the remission period (0.107±0.026 g/24 h, 1.53±0.27 mg/mmol Cr and 41.92±7.81 ng/l, respectively) and the healthy control group (0.098±0.027 g/24 h, 1.40±0.26 mg/mmol creatinine and 38.43±9.83 ng/l, respectively; P<0.05). During the remission period, urinary GAG and serum Ela levels in the LMWH+pred group were significantly reduced compared with the pred group (P<0.05), whereas proteinuria did not differ between these groups (P>0.05). Positive correlations were revealed between urinary GAG excretion and proteinuria (r=0.877; P<0.05), proteinuria and serum Ela levels (r=0.844; P<0.05) and serum Ela levels and urinary GAG excretion (r=0.881; P<0.05). The results of the present study indicated that elevated serum Ela levels may induce proteinuria by degrading GAGs in the glomerular basement membrane in children with SSNS. LMWH may benefit nephrotic remission of SSNS via inhibiting Ela.


A statistical approach to identify, monitor, and manage incomplete curated data sets.
Many biological knowledge bases gather data through expert curation of published literature. High data volume, selective partial curation, delays in access, and publication of data prior to the ability to curate it can result in incomplete curation of published data. Knowing which data sets are incomplete and how incomplete they are remains a challenge. Awareness that a data set may be incomplete is important for proper interpretation, to avoiding flawed hypothesis generation, and can justify further exploration of published literature for additional relevant data. Computational methods to assess data set completeness are needed. One such method is presented here. In this work, a multivariate linear regression model was used to identify genes in the Zebrafish Information Network (ZFIN) Database having incomplete curated gene expression data sets. Starting with 36,655 gene records from ZFIN, data aggregation, cleansing, and filtering reduced the set to 9870 gene records suitable for training and testing the model to predict the number of expression experiments per gene. Feature engineering and selection identified the following predictive variables: the number of journal publications; the number of journal publications already attributed for gene expression annotation; the percent of journal publications already attributed for expression data; the gene symbol; and the number of transgenic constructs associated with each gene. Twenty-five percent of the gene records (2483 genes) were used to train the model. The remaining 7387 genes were used to test the model. One hundred and twenty-two and 165 of the 7387 tested genes were identified as missing expression annotations based on their residuals being outside the model lower or upper 95% confidence interval respectively. The model had precision of 0.97 and recall of 0.71 at the negative 95% confidence interval and precision of 0.76 and recall of 0.73 at the positive 95% confidence interval. This method can be used to identify data sets that are incompletely curated, as demonstrated using the gene expression data set from ZFIN. This information can help both database resources and data consumers gauge when it may be useful to look further for published data to augment the existing expertly curated information.


Simultaneous multitone microwave emission by dc-driven spintronic nano-element.
Current-induced self-sustained magnetization oscillations in spin-torque nano-oscillators (STNOs) are promising candidates for ultra-agile microwave sources or detectors. While usually STNOs behave as a monochromatic source, we report here clear bimodal simultaneous emission of incommensurate microwave oscillations in the frequency range of 6 to 10 gigahertz at femtowatt level power. These two tones correspond to two parametrically coupled eigenmodes with tunable splitting. The emission range is crucially sensitive to the change in hybridization of the eigenmodes of free and fixed layers, for instance, through a slight tilt of the applied magnetic field from the normal of the nanopillar. Our experimental findings are supported both analytically and by micromagnetic simulations, which ascribe the process to four-magnon scattering between a pair of radially symmetric magnon modes and a pair of magnon modes with opposite azimuthal index. Our findings pave the way for enhanced cognitive telecommunications and neuromorphic systems that use frequency multiplexing to improve communication performance.


Structural basis for antibody targeting of the broadly expressed microbial polysaccharide poly-N-acetylglucosamine.
In response to the widespread emergence of antibiotic-resistant microbes, new therapeutic agents are required for many human pathogens. A non-mammalian polysaccharide, poly-N-acetyl-d-glucosamine (PNAG), is produced by bacteria, fungi, and protozoan parasites. Antibodies that bind to PNAG and its deacetylated form (dPNAG) exhibit promising in vitro and in vivo activities against many microbes. A human IgG1 mAb (F598) that binds both PNAG and dPNAG has opsonic and protective activities against multiple microbial pathogens and is undergoing preclinical and clinical assessments as a broad-spectrum antimicrobial therapy. Here, to understand how F598 targets PNAG, we determined crystal structures of the unliganded F598 antigen-binding fragment (Fab) and its complexes with N-acetyl-d-glucosamine (GlcNAc) and a PNAG oligosaccharide. We found that F598 recognizes PNAG through a large groove-shaped binding site that traverses the entire light- and heavy-chain interface and accommodates at least five GlcNAc residues. The Fab-GlcNAc complex revealed a deep binding pocket in which the monosaccharide and a core GlcNAc of the oligosaccharide were almost identically positioned, suggesting an anchored binding mechanism of PNAG by F598. The Fab used in our structural analyses retained binding to PNAG on the surface of an antibiotic-resistant, biofilm-forming strain of Staphylococcus aureus Additionally, a model of intact F598 binding to two pentasaccharide epitopes indicates that the Fab arms can span at least 40 GlcNAc residues on an extended PNAG chain. Our findings unravel the structural basis for F598 binding to PNAG on microbial surfaces and biofilms.


Stage III and IV endometrial cancer: a 20-year review of patients.
In advanced endometrial cancer, the importance of peritoneal cytology and optimal surgical cytoreduction remain subjects of discussion. We evaluated our clinical experience of 67 patients with FIGO stage III and IV endometrial cancer treated in the Erasmus Medical Centre in Rotterdam over a 20-year period with an emphasis on stage IIIA disease based on positive cytology only and optimal cytoreduction. Lymphadenectomy was not routinely performed and peritoneal cytology was examined in 74% of the patients. Stage IIIA disease was found in 33 patients, 10 of whom had positive cytology only. Analysis showed that incidence of recurrence and survival rates of patients with stage IIIA disease based on positive cytology only were comparable with stage IIIA disease based on other factors. In 50 patients, it was possible to remove all macroscopic tumor, whereas in 17 patients, an optimal cytoreduction was not achievable. The 2- and 5-year survival rates after optimal cytoreduction were 82.2% and 65.6%; where this could not be achieved, these figures were 50.8% and 40.6%. In advanced endometrial cancer patients, positive peritoneal cytology seems an important prognostic factor in stage IIIA disease if lymph node status is unknown. Survival is improved if optimal surgical cytoreduction is achievable.


Clinical utility of the Primary Care--PTSD Screen among U.S. veterans who served since September 11, 2001.
Posttraumatic stress disorder (PTSD) is a prevalent anxiety disorder that is often undetected among primary care patients. The Department of Veterans Affairs has implemented the Primary Care-PTSD Screen (PC-PTSD) to screen for PTSD; however, minimal research has examined its utility. This study was designed to assess the diagnostic accuracy of the PC-PTSD among veterans who had served since 9/11/2001, including operations in Afghanistan (Operation Enduring Freedom) and Iraq (Operation Iraqi Freedom). Signal detection analyses were used to evaluate the performance of the PC-PTSD and two other screens, the Davidson Trauma Scale (DTS) and the SPAN, in a sample of 220 veterans with military service since 9/11/2001. The reference standard for PTSD was Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) diagnosis based upon structured clinical interview. The impact of demographic variables on test performance was examined. A cutting score of 3 on the PC-PTSD maximized efficiency (85%; sensitivity=0.83; and specificity=0.85). Although analyses supported the utility of the PC-PTSD (area under the curve (AUC)=0.875), the measure was outperformed by both the DTS (AUC=0.944) and the SPAN (AUC=0.931). Results suggest that the PC-PTSD is an acceptable screen for PTSD among veterans. Within primary care settings, the PC-PTSD may be most advantageously employed in the context of staged screening, given the measure's relative susceptibility to false positives.


Screening for childhood mental health disorders using the Strengths and Difficulties Questionnaire: the validity of multi-informant reports.
This study investigated the diagnostic accuracy of the Strengths and Difficulties Questionnaire (SDQ) in a population of children born extremely preterm (<26wks gestation). Parents and teachers of 219 extremely preterm children (118 females, 101 males; age 11y) were asked to complete the SDQ to screen for psychological problems. Multi-informant ratings were aggregated using two methods: combined (parent or teacher rated the child with problems) and pervasive (parent and teacher rated the child with problems). Psychiatric diagnoses were assigned using the Development and Well-Being Assessment. Pervasive ratings had the greatest diagnostic accuracy for emotional disorders (89%), conduct disorders (94%), attention-deficit-hyperactivity disorder (ADHD; 90%), and autism spectrum disorders (ASDs; 94%), but were associated with low sensitivity (≤50%). For clinical use, combined ratings were best for detecting emotional disorders (sensitivity 77%, specificity 75%), conduct disorders (83%, 88%), and ADHD (85%, 72%). Parent ratings were best for ASDs (93%, 66%). Teacher ratings significantly improved prediction over parent ratings alone for conduct disorders (∆χ(2) =9.3, p=0.002) and ADHD (∆χ(2) =24.1, p<0.001) only. Multi-informant data are preferable for assessing most mental health outcomes using the SDQ. As an outcome measure, pervasive ratings have the best predictive accuracy. For screening, combined ratings are best for detecting ADHD and emotional and conduct disorders. For ASDs, parent ratings were best.


Enzymatic ligation creates discrete multinanoparticle building blocks for self-assembly.
Enzymatic ligation of discrete nanoparticle-DNA conjugates creates nanoparticle dimer and trimer structures in which the nanoparticles are linked by single-stranded DNA, rather than by double-stranded DNA as in previous experiments. Ligation was verified by agarose gel and small-angle X-ray scattering. This capability was utilized in two ways: first, to create a new class of multiparticle building blocks for nanoscale self-assembly and, second, to develop a system that can amplify a population of discrete nanoparticle assemblies.


[Clinical and genetic analysis of a Chinese family affected with X-linked Charcot-Marie-Tooth disease].
To study the clinical manifestations and identify causative mutations for a Chinese family affected with X-linked Charcot-Marie-Tooth disease. Clinical, electrophysiological and pathological features of the family were carefully analyzed by neurologists. Blood samples were obtained from the proband and other family members. Genomic DNA was extracted. Mutation analysis of GJB1 gene was analyzed with PCR and direct sequencing. The family has fit with X-linked inheritance, and the affected individuals have typical clinical manifestations. A c.614A>G (p.Asn205Ser) mutation was detected in the GJB1 gene in all affected individuals in the family. A c.614A>G (p.Asn205Ser) mutation of GJB1 gene is co-segregated with the disease phenotype in this family and probably underlies the disease.


Celeribacter marinus sp. nov., isolated from coastal seawater.
A Gram-staining-negative, non-motile, non-pigmented and rod-shaped bacterial strain, designated IMCC12053(T), was isolated from coastal surface seawater of the Yellow Sea, Korea. Optimal growth of strain IMCC12053(T) was observed at 30 °C, pH 7.0 and in the presence of 2 % (w/v) NaCl. 16S rRNA gene sequence comparisons showed that strain IMCC12053(T) was most closely related to Celeribacter baekdonensis L-6(T) (97.5 % similarity) and Celeribacter neptunius H 14(T) (96.0 %). Strain IMCC12053(T) formed a robust phylogenetic clade with members of the genus Celeribacter. The DNA-DNA relatedness value between IMCC12053(T) and C. baekdonensis was far lower than 70 % (35.7-42.5 %), which indicated that strain IMCC12053(T) is a novel genomic species of the genus Celeribacter. The major respiratory isoprenoid quinone was ubiquinone-10 (Q-10) and major polar lipids were phosphatidylglycerol, diphosphatidylglycerol, phosphatidylcholine and aminolipids. The DNA G+C content was 61.0 mol%. On the basis of genotypic and phenotypic data collected in this study, it is proposed that strain IMCC12053(T) represents a novel species of the genus Celeribacter, for which the name Celeribacter marinus sp. nov. is proposed. The type strain is IMCC12053(T) ( = KACC 17482(T) = NBRC 109702(T)).


Women in academic general surgery.
To portray the professional experiences of men and women in academic general surgery with specific attention to factors associated with differing academic productivity and with leaving academia. A 131-question survey was mailed to all female (1,076) and a random 2:1 sample of male (2,152) members of the American College of Surgeons in three mailings between September 1998 and March 1999. Detailed questions regarding academic rank, career aspirations, publication rate, grant funding, workload, harassment, income, marriage and parenthood were asked. A five-point Likert scale measured influences on career satisfaction. Responses from strictly academic and tenure-track surgeons were analyzed and interpreted by gender, age, and rank. Overall, 317 surgeons in academic practice (168 men, 149 women) responded, of which 150 were in tenure-track positions (86 men, 64 women). Men and women differed in academic rank, tenure status, career aspirations, and income. Women surgeons had published a median of ten articles compared with 25 articles for men (p <.001). Marriage or parenthood did not influence numbers of publications for women. Overall career satisfaction was high, but women reported feeling career advancement opportunities were not equally available to them as to their male colleagues and feeling isolation from surgical peers. Ten percent to 20% of surgeons considered leaving academia, with women assistant professors (29%) contemplating this most commonly. Addressing the differences between men and women academic general surgeons is critical in fostering career development and in recruiting competitive candidates of both sexes to general surgery.


Comparative effectiveness and harms of long-acting insulins for type 1 and type 2 diabetes: A systematic review and meta-analysis.
To review evidence comparing benefits and harms of long-acting insulins in patients with type 1 and 2 diabetes. MEDLINE and two Cochrane databases were searched during February 2018. Two authors selected studies meeting inclusion criteria and assessed their quality. Comparative studies of adult or paediatric patients with diabetes treated with insulin degludec, detemir or glargine were included. Meta-analysis was used to combine results of similar studies, and the I2 statistic calculated to assess statistical heterogeneity. Of 2534 citations reviewed, 70 studies met the inclusion criteria. No statistically significant differences in HbA1c were seen between any two insulins or formulations. Hypoglycaemia was less probable with degludec than with glargine, including nocturnal hypoglycaemia in type 1 (rate ratio 0.68, 95% CI 0.56-0.81) and type 2 diabetes (rate ratio 0.73, 95% CI 0.65-0.82), and severe hypoglycaemia in type 2 diabetes (relative risk 0.72, 95% CI 0.54-0.96). Patients with type 2 diabetes had higher rates of withdrawal because of adverse events when treated with detemir compared with glargine (relative risk 2.1, 95% CI 1.4-3.3). Adults taking detemir gained about 1 kg less body weight than those taking degludec (type 1) or glargine (type 2). No differences in glycaemic control were seen between insulin degludec, detemir and glargine. Hypoglycaemia was less probable with degludec than glargine, and patients taking detemir gained less body weight than those given degludec or glargine. In type 2 diabetes, withdrawals as a result of adverse events were more probable with detemir than glargine.


Control and treatment of type 2 diabetes in private patients in the Egyptian "DIACONTROL study".
This study aims to identify the characteristics of Egyptian patients suffering from type 2 diabetes mellitus (T2DM), determine disease control rates, and gain insights into clinical treatments. A total of 2,516 patients with T2DM were recruited from 244 private clinics across Egypt in a one-month period from May to June 2017. Data collected from patients included glycemic control parameters of glycosylated hemoglobin, fasting plasma glucose, and postprandial glucose. Additional information gathered included patients' weight, age, level of physical activity, smoking habits, presence of comorbidities, type of treatment received for type 2 diabetes, number and severity of hypoglycemic events, as well as treatment modification by the physician in the last visit. The type of statistics used for the analysis is descriptive statistics and regression model. Only 18.4% of participating patients achieved the target level of glycosylated hemoglobin of 7% or below. The mean age of these patients was 54±11.2 years, and the mean duration since the first diagnosis was 6.6±6.4 years. A total of 33.4% of all patients had no known comorbidity, while the rest had one or more known and treated comorbidities. A total of 76% of patients received sulfonylurea either as monotherapy or in combination with other treatments. In addition, no treatment modifications or adjustments were provided for 32% of the study participants who did not reach their glycemic control target. In Egypt, there is a low rate of glycemic control among private patients and a high prevalence of comorbid conditions. This is likely to cause a significant health burden to people with T2DM, the healthcare system, and the economy due to a loss in productivity. This study presented an argument for better-managed measures to improve glycemic control in the population, such as patient education to increase patient awareness and adherence to treatment protocols as well as improved adherence to guidelines by clinicians.


Long-term remission despite clonal expansion of replication-competent HIV-1 isolates.
Clonal expansion of T cells harboring replication-competent virus has recently been demonstrated in patients on suppressive antiretroviral therapy (ART) regimens. However, there has not been direct evidence of this phenomenon in settings of natural control, including in posttreatment controllers who maintain control of viral replication after treatment when ART is discontinued. We present a case of an individual who has had undetectable viral loads for more than 15 years following the cessation of ART. Using near-full-genome sequence analysis, we demonstrate that 9 of 12 replication-competent isolates cultured from this subject were identical and that this identity was maintained 6 months later. A similar pattern of replication-competent virus clonality was seen in a treatment-naive HLA-B*57 elite controller. In both cases, we show that CD8+ T cells are capable of suppressing the replication of the clonally expanded viruses in vitro. Our data suggest that, while clonal expansion of replication-competent virus can present a barrier to viral eradication, these viral isolates remain susceptible to HIV-specific immune responses and can be controlled in patients with long-term suppression of viral replication.


The 2.1-A crystal structure of an archaeal preinitiation complex: TATA-box-binding protein/transcription factor (II)B core/TATA-box.
Archaea possess a basal transcriptional apparatus that resembles that of eukaryotes. Here we report the 2.1-A crystal structure of the archaeal transcription factor complex formed by the TATA-box-binding protein (TBP), the transcription factor IIB homolog, and a DNA target, all from the hyperthermophile Pyrococcus woesei. The overall fold of these two basal transcription factors is essentially the same as that of their eukaryotic counterparts. However, in comparison with the eukaryotic complexes, the archaeal TBP-DNA interface is more symmetrical, and in this structure the orientation of the preinitiation complex assembly on the promoter is inverted with respect to that seen in all crystal structures of comparable eukaryotic systems. This study of the structural details of an archaeal transcription factor complex presents the opportunity to examine the evolution of the basal eukaryotic transcriptional apparatus from a stereochemical viewpoint and to extend our understanding of the physical biochemistry of transcriptional initiation.


Considerations for managing the airway in the ENT patient.
Anesthesiologists may encounter particularly challenging airway management problems and anesthetic requirements for any surgical procedure. However, this is frequently the case with ENT surgery and its patient population. Sharing the airway with the surgeon requires a special understanding of the procedure to be undertaken, clear communication, and cooperation. Basic knowledge concerning the airway anatomy and physiology is essential. Special ENT procedures require special skills. Anesthesiologists may be required to secure an airway in an unconventional manner in these patients, as well as use special ventilation methodology and challenging anesthesia techniques.


[Spontaneous perirenal hematoma secondary to hydronephrosis in pelvic kidney].
Contribution of one case of Spontaneous Perirenal Haematoma (SPH) secondary to hydronephrosis accompanied by lithiasis in pelvic kidney. SPH can result from multiple causes, the most frequent ones being renal tumours, most particularly angiomyolipoma and hypernephroma. Hydronephrosis is an uncommon cause of SPH, and very few cases are described in the literature. The present paper addresses the diagnostic usefulness of the various radiological tests as well as the therapeutical approach to be followed.


Asymmetrical perception of body rotation after unilateral injury to human vestibular cortex.
Vestibular information plays a key role in many perceptual and cognitive functions, but surprisingly little is known about how vestibular signals are processed at the cortical level in humans. To address this issue, we tested the ability of two patients, with damage to key components of the vestibular network in either the left or right hemisphere, to perceive passive whole-body rotations (25-125 degrees) about the yaw axis. In both patients, the posterior insula, hippocampus, putamen, and thalamus were extensively damaged. The patients' responses were compared with those of nine age- and sex-matched neurologically intact participants. The body rotations were conducted without vision and the peak angular velocities ranged from 40 degrees to 90 degrees per second. Perceived rotation was assessed by open-loop manual pointing. The right hemisphere patient exhibited poor sensitivity for body rotations toward the contralesional (left) hemispace and generally underestimated the rotations. By contrast, his judgments of rotations toward the ipsilesional (right) hemispace greatly overestimated the physical rotation by 50-70 degrees for all tested magnitudes. The left hemisphere patient's responses were more appropriately scaled for both rotation directions, falling in the low-normal range. These findings suggest that there is some degree of hemispheric specialization in the cortical processing of dynamic head rotations in the yaw plane. In this view, right hemisphere structures play a dominant role, processing rotations in both directions, while left hemisphere structures process rotations only toward the contralesional hemispace.


Dietary Supplementation With Fine-Grinding Wheat Bran Improves Lipid Metabolism and Inflammatory Response via Modulating the Gut Microbiota Structure in Pregnant Sow.
This study investigated the effects of fine-grinding wheat bran on pregnant sow body condition, lipid metabolism, inflammatory response, and gut microbiota. In this study, wheat bran was crushed into three particle sizes. A total of 60 Landrace × Yorkshire second parity sows were allotted to two groups: CWB (a diet containing coarse wheat bran with particle size of 605 μm) and FWB (a diet containing fine wheat bran with particle size of 438 μm). Fine-grinding wheat bran had higher soluble dietary fiber concentration, swelling capacity, water-holding capacity, and fermentability than coarse wheat bran. Pregnant sows fed FWB throughout pregnancy had lower body weight and fat deposition than sows fed CWB. And the piglet body weight at birth of the FWB group was remarkably increased. Serum concentrations of lipids (triglycerides, total cholesterol, and free fatty acid), interleukin 6, leptin, and resistin were decreased on day 90 of pregnancy by fine wheat bran supplementation. Feeding FWB significantly decreased abundance of Firmicutes and dramatically increased the abundance of Bacteroidetes at phylum level. At genus level, the abundance of Terrisporobacter was decreased in FWB feeding sows, but the abundance of Parabacteroides was increased. Fecal total short-chain fatty acids, propionate, and butyrate contents were markedly increased in the FWB group. The results suggested that the physicochemical properties of finely ground wheat bran had been improved. Dietary supplementation with fine wheat bran changed the gut microbiota structure and enhanced the short-chain fatty acids level, which improved the maternal body condition, metabolic and inflammatory status, and reproductive performance in sows.


Anti-mouse properdin TSR 5/6 monoclonal antibodies block complement alternative pathway-dependent pathogenesis.
The complement alternative pathway (AP) is a major contributor to a broad and growing spectrum of diseases that includes age-related macular degeneration, atypical hemolytic uremic syndrome, and preeclampsia. As a result, there is much interest in the therapeutic disruption of AP activity. Properdin, the only positive regulator of the AP, is a particularly promising AP target. Several issues need to be clarified before the potential for properdin-directed therapy can be realized. In this report we use a portion of the mouse properdin protein, expressed in a bacterial system, to raise rabbit polyclonal and hamster monoclonal antibodies that block properdin-dependent pathogenesis. These antibodies, when employed with AP-dependent mouse disease models, can help evaluate the feasibility of properdin-directed therapy.


Effectiveness of pandemic and seasonal influenza vaccines in preventing pandemic influenza-associated hospitalization.
Vaccines are leading pharmacological measures for limiting the impact of pandemic influenza in the community. The objective of this study was to investigate the effectiveness of influenza (pandemic and seasonal) vaccines in preventing pandemic influenza-associated hospitalization. We conducted a multicenter matched case-control study in 36 Spanish hospitals. Patients hospitalized with confirmed pandemic influenza between November 2009 and February 2010 and two hospitalized controls per case, matched according to age, date of hospitalization and province of residence, were selected. Multivariate analysis was performed using conditional logistic regression. Subjects were considered vaccinated if they had received the vaccine >14 days (seasonal influenza vaccine) or >7 days (pandemic influenza vaccine) before the onset of symptoms (cases) or the onset of symptoms of the matched case (controls). For the pandemic influenza vaccine, vaccination effectiveness (VE) was estimated taking into account only patients recruited from November 23, 2009, seven days after the beginning of the pandemic influenza vaccination campaign. 638 cases and 1250 controls were included. The adjusted VE of the pandemic vaccine in the ≥18 years age group was 74.2% (95% CI, 29-90) and that of the influenza seasonal vaccine 15.0% (-34 to 43). The recommendation of influenza vaccination should be reinforced as a regular measure to reduce influenza-associated hospitalization during pandemics and seasonal epidemics.


Corticosteroids for the inflammatory response to cardiopulmonary bypass: an update.
Cardiac surgery and cardiopulmonary bypass are associated with an intense activation of the immune system. The systemic inflammatory response that develops in many cardiac surgical patients has the potential to lead to significant postoperative morbidity, and even mortality. Intraoperative corticosteroids are often used as prophylaxis for this systemic inflammatory response. This update provides a review of the existing evidence of the effects of corticosteroids on clinical outcomes after cardiopulmonary bypass, and combines this with emerging evidence from a recently published first large clinical trial of dexamethasone in cardiac surgery.


Decreased CB receptor binding and cannabinoid signaling in three brain regions of a rat model of schizophrenia.
Schizophrenia is a serious mental health disorder characterized by several behavioral and biochemicel abnormalities. In a previous study we have shown that mu-opioid (MOP) receptor signaling is impaired in specific brain regions of our three-hit animal model of schizophrenia. Since the cannabinoid system is significantly influenced in schizophrenic patients, in the present work we investigated cannabinoid (CB) receptor binding and G-protein activation in cortical, subcortical and cerebellar regions of control and 'schizophrenic' rats. Cannabinoid agonist (WIN-55,212-2 mesylate) mediated G-protein activation was consistently decreased in all areas tested, and the difference was extremely significant in membranes prepared from the cerebellum. Interestingly, the cerebellar activity of WIN-55,212-2 stimulated G-proteins was substantially higher than those of cerebral cortex and subcortical region in control animals, indicating a primordial role of the cannabinoid system in the cerebellum. At the level of radioligand binding, the affinities of the CB receptors were also markedly decreased in the model animals. Capacity of the [3H]WIN-55,212-2 binding was only higher in the cerebellum of 'schizophrenic' model rats. Taken together, in all three brain areas of model rats both cannabinoid receptor binding and cannabinoid agonist-mediated G-protein activation were regularly decreased. Our results revealed that besides the opioids, the endocannabinoid - cannabis receptor system also shows impairment in our rat model, increasing its face validity and translational utility.