Investigation of Cysticercosis bovis prevalence using passive abattoir post-mortem inspection and active administration of structured non-participatory questionnaire to farmers in Botswana.
Most government published statistics of C. bovis prevalence in Botswana emanate mainly from records available at the Botswana Meat Commission (BMC), the country's national export abattoir. Although BMC slaughters 44% of Botswana's annual cattle slaughter, prevalence data arising from BMC does not reflect prevalence from lower throughput abattoirs and potential hotspots. Thus, reporting national prevalence rate using solely BMC statistics may not be very informative and reflective of the bigger picture. It therefore became imperative to probe prevalence of bovine cysticercosis using a cross-sectional study through passive abattoir inspection, covering a wider scope (more regions) and some lower throughput abattoirs previously not accounted for. Furthermore, non-participatory interview using structured questionnaires was employed to actively elicit prevalence information directly from meat industry stake holders. Prevalence arising from survey was used to compare and query results from statutory (traditional) passive abattoir method. Abattoir prevalence was 17.17% (SE = 1.70027), and survey prevalence was 42.35%; both of which were higher than published prevalence of 13.5% and BMC prevalence of 10% (SE = 0.006576). Survey method was more holistic than passive abattoir method, by covering more frontiers thus yielding higher prevalence. At p = 025, abattoir and survey prevalence were significantly different from each other. In addition to delimitating novel hotspots in Botswana, this study showed significant difference, p = 0.002 in prevalence within districts and regions. Kalagadi district's prevalence differed significantly from other districts: differed from North East at p = 0.042, Central district at p = 0.002 and Ghanzi at p = 0.004. The results which arise from this methodological approach have been able to provide a more all-inclusive and reliable prevalence rate.


Platelet-derived growth factor modulation of focal adhesion kinase (p125FAK) and paxillin tyrosine phosphorylation in Swiss 3T3 cells. Bell-shaped dose response and cross-talk with bombesin.
In the present study, we have identified several proteins in Swiss 3T3 cells that are phosphorylated on tyrosine in response to platelet-derived growth factor (PDGF) and exhibit an unusual bell-shaped dose-response curve with a maximum at 5 ng/ml platelet-derived growth factor (PDGF). These proteins include two that are associated with focal adhesions, namely the focal adhesion kinase (p125FAK), a novel cytosolic tyrosine kinase, and paxillin. At low concentrations of PDGF (1-5 ng/ml), these proteins are the predominant tyrosine-phosphorylated species. At 30 ng/ml PDGF, however, there was no stimulation of their phosphorylation over control levels. In contrast, tyrosine phosphorylation of previously described substrates of the PDGF receptor tyrosine kinase, namely the p21ras GTPase-activating protein, p120, phosphatidyl inositol 3' kinase, and phospholipase C gamma exhibited sigmoidal dose-response curves with PDGF and were all efficiently phosphorylated on tyrosine at 30 ng/ml PDGF. Cytochalasin D, which disrupts the actin cytoskeleton, completely inhibited the tyrosine phosphorylation of p125FAK and paxillin by PDGF. Examination of the actin cytoskeleton after stimulation of cells with different concentrations of PDGF revealed that at 5 ng/ml PDGF, actin appears in stress fibers and in membrane ruffles, while at 30 ng/ml, PDGF disrupts the actin cytoskeleton. Bombesin stimulates actin stress fiber formation with no evidence of disruption of stress fibers at high concentrations. When cells were stimulated with bombesin (10 nM) in the presence of 30 ng/ml PDGF, however, the actin cytoskeleton was completely disrupted. Further, the tyrosine phosphorylation of both p125FAK and paxillin induced by bombesin (10 nM) was completely prevented when cells were stimulated with bombesin in the presence of 30 ng/ml PDGF. We propose that the inhibitory limb in the bell-shaped dose-response curve of PDGF and the novel cross-talk between PDGF and bombesin on tyrosine phosphorylation may be explained by the ability of PDGF at 30 ng/ml to disrupt the actin cytoskeleton.


Ontogeny of CTX expression in xenopus.
In Xenopus, the type I transmembrane protein, CTX (cortical thymocyte-specific antigen of Xenopus), is hypothesized to play a role in thymocyte differentiation and/or thymic selection. The present studies were undertaken to gather additional evidence in support of a postulated association of CTX with a differentiation step of a cell population that corresponds to the murine immature double positive (CD4+CD8+TCR+) thymocyte subset. During ontogeny, cell surface expression of CTX on thymocytes can first be detected by immunocytochemistry and flow cytometry at 8 days post-fertilization, about 1 day after CD8+ cells first appear. By 12 days post-fertilization, T-cells in the entire cortex except for the outer most layer of cells, are intensely CTX positive, whereas those in the medulla are negative. This pattern persists throughout larval and postmetamorphic life.


Protonation states of the catalytic intermediates of cytochrome c oxidase.
Protonation changes accompanying conversion of oxidised (O state) cytochrome c oxidase to the 2-electron-reduced P state, and 3-electron-reduced F state at pH 8.0 have been measured. It was found that 2 and 3 protons, respectively, were taken up. The fourth proton required for the reduction of O2 to H2O must therefore be consumed in the remaining F----O portion of the catalytic cycle.


Trace metal distributions in the sediments of the Little Akaki River, Addis Ababa, Ethiopia.
The levels and distribution of trace metals (Cr, Mn, Co, Ni, Cu, Zn, Cd and Pb) at eleven water and sediment stations on the Little Akaki River (LAR) in Addis Ababa, Ethiopia, were determined. The binding forms of the metals in various geochemical fractions of the sediments were also quantified. The molar ratio of the sum of the simultaneously extractable metals (∑SEM) and acid-volatile sulphide (AVS)-as a measure for predicting metal-induced toxicity-was estimated. LAR trace levels in water for Cu, Zn, and, particularly Mn were, in most instances, higher than the recommended guidelines for healthy aquatic ecosystems. Total trace metal (TTM) contents in the LAR sediments at certain stations exceeded "threshold effect concentrations" and even "probable effect concentrations", especially in the cases of Zn, Cu, Ni, Pb, and at all stations for Mn. This became more apparent after applying "normalizations" to the relatively lower TTM adsorption capacities of coarse-grained, organic-poor sediments. Sequential extraction of the sediments showed that trace metals generally have a higher affinity for Fe-Mn oxide and organic matter/sulphidic fractions, followed by the residual fraction. Mn was relatively strongly bound to the exchangeable, carbonate bound fractions, whereas a large proportion of Cr was found in the residual fraction. The Σ[SEM]/[AVS] ratio pointed to potential metal-induced toxicity of sediments collected from seven out of the eleven stations. The results indicate that trace metal pollution pose risks to the health of ecosystems, and to human communities that use the river for a range of different purposes.


QUICK (QUick Index to Caduceus Knowledge): using the INTERNIST-1/CADUCEUS knowledge base as an electronic textbook of medicine.
QUICK (QUick Index to Caduceus Knowledge), is a prototypical user-friendly access system which adapts the INTERNIST-1/CADUCEUS knowledge base for use as an electronic textbook of medicine. The QUICK program can be used both as a diagnostic aid and a teaching tool in the field of internal medicine. A preliminary evaluation of a prototypical version of QUICK was conducted in order to identify its strengths and weaknesses. QUICK was made available to the medical housestaff at three Pittsburgh area teaching hospitals for a period of 2 months. Most users felt QUICK was educational and wanted future access to the system. An examination of log files revealed the users' most frequently encountered difficulties. Using the INTERNIST-I knowledge base as an electronic textbook expands the project's intended audience by providing clinical support for a broad group of diagnostic problems.


Serial ChIP as a tool to investigate the co-localization or exclusion of proteins on plant genes.
Establishing transcriptional regulatory networks that include protein-protein and protein-DNA interactions has become a key component to better understanding many fundamental biological processes. Although a variety of techniques are available to expose protein-protein and protein-DNA interactions, unequivocally establishing whether two proteins are targeted together to the same promoter or DNA molecule poses a very challenging endeavour. Yet, the recruitment of multiple regulatory proteins simultaneously to the same promoter provides the basis for combinatorial transcriptional regulation, central to the transcriptional regulatory network of eukaryotes. The serial ChIP (sChIP) technology was developed to fill this gap in our knowledge, and we illustrate here its application in plants. Here we describe a modified sChIP protocol that provides robust and quantitative information on the co-association or exclusion of DNA-binding proteins on particular promoters. As a proof of principle, we investigated the association of histone H3 protein variants with modified tails (H3K9ac and H3K9me2) with Arabidopsis RNA polymerase II (RNPII) on the promoter of the constitutively expressed actin gene (At5g09810), and the trichome-expressed GLABRA3 (GL3) gene. As anticipated, our results show a strong positive correlation between H3K9ac and RNPII and a negative correlation between H3K9me2 and RNPII on the actin gene promoter. Our findings also establish a weak positive correlation between both H3K9ac and H3K9me2 and RNPII on the GL3 gene promoter, whose expression is restricted to a discrete number of cell types. We also describe mathematical tools that allow the easy interpretation of sChIP results. The sChIP method described here provides a reliable tool to determine whether the tethering of two proteins to the same DNA molecule is positively or negatively correlated. With the increasing need for establishing transcriptional regulatory networks, this modified sChIP method is anticipated to provide an excellent way to explore combinatorial gene regulation in eukaryotes.


[Clinical psychology in rehabilitative cardiology - a working model (author's transl)].
The article presents a model for the psychological treatment within the framework of an in-patient rehabilitation programme for patients suffering from heart and circulatory diseases. On the basis of research work investigating the psychological factors of heart diseases, this model describes details of a clinical-psychological intervention and psychotherapeutic/psychosomatic supervision tested over a two-year period at a specialised rehabilitation centre for heart and circulatory diseases.


Kinetic analysis of human metallothionein and CdTe quantum dot complexes using fluorescence and voltammetry techniques.
Thanks to quantum dots' (QDs) properties, they can be used as selective and sensitive biomarkers in molecular imaging. In a previous paper, we confirmed the possibility of interaction between mercaptosuccinic acid-capped cadmium telluride QDs (MSA-CdTe) and human metallothionein (MT). The aim of this study was to expand on our previous research with an evaluation of the stability of the formed complexes between human MT and four CdTe compounds of the following sizes: 3.4nm (blue QDs), 3.8nm (green QDs), 4.5nm (yellow QDs), and 5.2nm (red QDs). Complexes were evaluated over time using fluorescence intensity and differential pulse voltammetry. Differences between the voltammograms obtained for standard solutions and for CdTe+MT show that complexes were formed. An increase in fluorescence intensity was observed for blue (Δ%≈40 for t=1→120min) and red (Δ%≈30 for t=1→120min) CdTe-MT complexes than CdTe alone, whereas green and yellow CdTe-MT complexes had a lower fluorescence intensity than CdTe alone. A stronger time dependence of the mercaptosuccinic acid (MSA) peak height on the timeline and differences in the MSA peak shape (in CdTe, and CdTe+MT complexes) were also observed by voltammetry. Authors noticed a decrease in the Cat2 signal of the red and green CdTe+MT complexes at the time of conjugation. Our results reveal that the size of QDs has an impact on the interaction between CdTe and human MT, as well as on the stability of complexes formed during these interactions. The bioconjugates' stability was also found to depend on the time of interaction.


Additional transbronchial needle aspiration through a guide sheath for peripheral pulmonary lesions that cannot be detected by radial EBUS.
Endobronchial ultrasound with a guide sheath (EBUS-GS) has resulted to better diagnostic outcome for peripheral pulmonary lesions (PPLs), although the yield is not satisfactory for lesions that cannot be located by EBUS. We aimed to evaluate whether the addition of a new technique, transbronchial needle aspiration through a guide sheath (GS-TBNA), can increase the yield for these cases. This was a retrospective review of cases that were not located by EBUS during EBUS-GS for PPL diagnosis. From September 2012 to August 2014, 67 PPLs had 'invisible' EBUS-GS location prior to transbronchial sampling. The patients were divided into two groups according to the use of additional GS-TBNA: GS-TBNA group (n=22) and non-GS-TBNA group (n=45). Diagnostic yields were compared and multivariate analysis was performed to determine the factors associated with increased diagnostic yield. The diagnostic yield was significantly higher in the GS-TBNA group than in the non-GS-TBNA group (54.5% vs 17.8%, P<0.01). The complication rate was not significantly different between the GS-TBNA group and the non-GS-TBNA group (0% vs 4.4%, P=1.0). Multivariate analysis showed that only performing GS-TBNA was significantly associated with increased diagnostic yield (odds ratio 3.99, P=0.03). GS-TBNA is a safe technique for PPL diagnosis and may be useful when the EBUS probe cannot reach the lesion.


A generic method for improving the spatial interoperability of medical and ecological databases.
The availability of big data in healthcare and the intensive development of data reuse and georeferencing have opened up perspectives for health spatial analysis. However, fine-scale spatial studies of ecological and medical databases are limited by the change of support problem and thus a lack of spatial unit interoperability. The use of spatial disaggregation methods to solve this problem introduces errors into the spatial estimations. Here, we present a generic, two-step method for merging medical and ecological databases that avoids the use of spatial disaggregation methods, while maximizing the spatial resolution. Firstly, a mapping table is created after one or more transition matrices have been defined. The latter link the spatial units of the original databases to the spatial units of the final database. Secondly, the mapping table is validated by (1) comparing the covariates contained in the two original databases, and (2) checking the spatial validity with a spatial continuity criterion and a spatial resolution index. We used our novel method to merge a medical database (the French national diagnosis-related group database, containing 5644 spatial units) with an ecological database (produced by the French National Institute of Statistics and Economic Studies, and containing with 36,594 spatial units). The mapping table yielded 5632 final spatial units. The mapping table's validity was evaluated by comparing the number of births in the medical database and the ecological databases in each final spatial unit. The median [interquartile range] relative difference was 2.3% [0; 5.7]. The spatial continuity criterion was low (2.4%), and the spatial resolution index was greater than for most French administrative areas. Our innovative approach improves interoperability between medical and ecological databases and facilitates fine-scale spatial analyses. We have shown that disaggregation models and large aggregation techniques are not necessarily the best ways to tackle the change of support problem.


Early maternal Zika infection predicts severe neonatal neurological damage: results from the prospective Natural History of Zika Virus Infection in Gestation cohort study.
To define the prevalence of adverse outcomes of maternal infection in a large cohort of ZIKV-infected Brazilian women and their infants. Prospective population-based cohort study. Ribeirão Preto's region's private and public health facilities. Symptomatic ZIKV-infected mothers and their infants. Prenatal/early neonatal data were obtained for all mother-child pairs. A subgroup of infants had cranial ultrasonography, eye fundoscopy, hearing and neurological examinations and Bayley III screening tests within 3 months of age. Prevalence of pregnancy losses and anomalies detected at birth or within 3 months according to the gestational age of infection. Overall, 511 ZIKV-infected women were identified from a total of 1116 symptomatic women; as there were two twins, there were a total of 513 fetuses included. Of these, 13 (2.5%; 95% CI 1.5-4.3) presented with major signs of congenital Zika syndrome (CZS). Of the 511 women, there were 489 livebirths and 24 (4.7%) pregnancy losses (20 miscarriages and four stillbirths). ZIKV-related anomalies occurred in the offspring of 42/511 (8.2%) mothers. Microcephaly or other CNS malformations were diagnosed in 1/4 (25.0%) stillbirths and in 19/489 (3.9%; 95% CI 2.5-5.9) of the liveborn infants. Fetal abnormalities were 14.0 (95% CI 7.6-26.0) times more likely with gestational infection occurring in ≤11 weeks. On follow up of 280 asymptomatic infants, 2/155 (1.3%) had eye abnormalities, 1/207 (0.5%) had CNS imaging findings and 16/199 (8%) presented neurological alert signs. This prospective population-based study represents the largest Brazilian cohort study of ZIKV in pregnancy. Congenital anomalies potentially associated with CZS are less frequent than previously thought. There is a strong association between the gestational age of infection (≤11 weeks) and a poorer early infant prognosis. A notable proportion of apparently asymptomatic newborns can present with subclinical findings within 3 months of age. ZIKV and pregnancy: adverse outcomes are less common, more prevalent for first-trimester infections, and potentially subclinical.


Status of the health information system in Ireland and its fitness to support health system performance assessment: a multimethod assessment based on stakeholder involvement.
Between 2019 and 2021, the first Irish health system performance assessment (HSPA) framework was developed. As routinely collected health data are necessary to continuously populate indicators of an HSPA framework, a purpose-driven assessment of the health information system (HIS) in Ireland and its fitness to support the implementation of an HSPA framework was conducted. This study reports on the status of the Irish HIS through a multimethod assessment based on continuous broad stakeholder involvement. Between May and November 2020, over 50 informants were engaged in individual and group interviews and stakeholder consultation workshops as part of the HIS assessment process. Descriptive themes and high-level data availability heatmaps were derived from interview and workshop data using thematic analysis. Indicator "passports" for the HSPA framework were populated during stakeholder consultation workshops and analysed using univariate descriptive statistics. The HIS in Ireland was able to provide administrative, survey and registry-based data for public sector acute care services, focusing on structure, process and output metrics. Significant data availability gaps, most notably from primary care, private hospitals and community care, were reported, with little availability of electronic health record and people-reported data. Data on outcome metrics were mostly missing, as were linkage possibilities across datasets for care pathway monitoring. The COVID-19 pandemic highlighted the national HIS's shortcomings but also the capacity for rapid development and improvement. A tailor-made assessment of the HIS in Ireland, involving a broad set of relevant stakeholders, revealed strengths, weaknesses and areas for improvement in the Irish health data landscape. It also contributed to the development of a national HSPA framework and momentum to further strengthen data infrastructure and governance, while working towards a more data-driven and person-centred healthcare system. This work demonstrates the utility of an inclusive HIS assessment process and is applicable beyond Ireland, where this case study was conducted.


Characterization of microvascular cell cultures from normotensive and hypertensive rat brains: pericyte-endothelial cell interactions in vitro.
We used specific markers and fluorescence microscopy to identify and characterize cerebrovascular cells. Cultures were derived from brain microvessels isolated from normotensive (Wistar Kyoto, WKY) and spontaneously hypertensive (SHR) rat brains prior to, coincident with and following the onset of chronic hypertension. Endothelial cells were characterized using di-acyl LDL and non-muscle isoactin-specific antibodies. Cerebrovascular pericytes were identified with the anti-muscle and non-muscle actin antibody staining. Using this combination of cell culture and fluorescence localization, we have been able to demonstrate that brain pericytes are tightly associated with the endothelial cells of the hypertensive-prone and hypertensive cell cultures, but not with the normotensive endothelial cultures. While the endothelial-pericyte ratio in the hypertensive-prone microvascular cultures was between 5:1 and 10:1, the number of pericytes associated with the hypertensive rat brain cultures increased two to five times (2:1-1:1). Muscle and non-muscle actin antibody staining localized the spindle-shaped pericytes of the hypertensive microvascular colonies. Pericytes were found overlaying and encircling the endothelial cells. Normotensive pericytes were not endothelial-associated. Whereas the hypertensive pericyte is devoid of stress fibers, the normotensive pericyte is a larger, spread-out cell possessing numerous stress fibers rich in muscle and non-muscle actin. These results provide the first evidence that the etiology and inception of cerebrovascular disease may be pericyte-related and suggest that pericyte contraction could play a pivotal role in regulating the flow of blood within the brain microcirculation.


Phase I study of the combination of quinacrine and erlotinib in patients with locally advanced or metastatic non small cell lung cancer.
Introduction Preclinical data suggest quinacrine acts as an inhibitor of FACT (facilitates chromatin transcription) complex, which may play a role in TKI (tyrosine kinase inhibitor) resistance. The aim of this Phase I study was to study the safety and assess the maximum tolerated dose of quinacrine in combination with erlotinib in non small cell lung cancer (NSCLC). Methods This was a phase I study with standard 3 + 3 dose escalation design with the primary aim of determining the maximum tolerated dose. Two of 3 patients enrolled at dose level 1 experienced dose limiting toxicity (DLT). The next 6 patients were enrolled at dose level - 1 and none of these 6 patients experienced DLT. The dose of 50 mg of quinacrine every other day with 150 mg of erlotinib was established as the maximum tolerated and the recommended phase II dose. One of 3 patients treated at dose level 1 had stable disease. One of 6 patients treated at dose level - 1 had partial response for 6 months, the rest had progressive disease at the time of first assessment. Conclusion Combination of quinacrine and erlotinib was well tolerated but showed limited efficacy in advanced NSCLC.


A randomized trial of dural puncture epidural technique compared with the standard epidural technique for labor analgesia.
We designed this prospective, double-blind, randomized study to examine whether a dural puncture without intrathecal drug administration immediately before epidural drug administration would improve labor analgesia when compared to a traditional epidural technique without prior dural puncture. Eighty nulliparous parturients with cervical dilation less than 5 cm were randomly assigned to receive a standardized epidural technique, with or without a single dural puncture with a 25-gauge (G) Whitacre spinal needle. After successful placement of the needle(s) and the epidural catheter, 12 mL of bupivacaine 2.5 mg/mL was administered through the epidural catheter and a patient-controlled epidural infusion of bupivacaine 1.25 mg/mL + fentanyl 2 mug/mL was initiated. The presence of sacral analgesia (S1) and pain scores were compared between groups. In demographically similar groups, parturients with prior dural puncture had more frequent blockade of the S1 dermatome (absolute risk difference [95% confidence interval] 22% [6-39]), more frequent visual analog scale scores <10/100 at 20 min (absolute risk difference 20% [1-38]), and reduced one-sided analgesia (absolute risk difference [95% CI] 17% [2-330]). The highest median sensory level (T10) was no different between groups. Dural puncture with a 25-G spinal needle immediately before the initiation of epidural analgesia improves the sacral spread, onset, and bilateral pain relief produced by analgesic concentrations of bupivacaine with fentanyl in laboring nulliparous patients.


Rational Engineering of BODIPY-Bridged Trisindole Derivatives for Solar Cell Applications.
Boron dipyrromethene (BODIPY) and its derivatives are known to be efficient photon-harvesting chromophores. However, their study as active materials in bulk heterojunction (BHJ) solar cells is still scarce. In this study, the development of new synthetic ways to design original BODIPY-based dumbbell-shape molecules, including a first 2,3,5,6-tetravinyl aromatic BODIPY molecule, is reported. High fill factors can be obtained in BHJ solar cells when blended with a fullerene derivative, leading to a new record BODIPY-based power conversion efficiency of 5.8 %.


Ultra-sensitive detection of ecologically rare fish from eDNA samples based on the RPA-CRISPR/Cas12a technology.
Environmental DNA (eDNA) research holds great promise for improving biodiversity science and conservation efforts by enabling worldwide species censuses in near real-time. Current eDNA methods face challenges in detecting low-abundance ecologically important species. In this study, we used isothermal recombinase polymerase amplification (RPA)-CRISPR/Cas detection to test Ctenopharyngodon idella. RPA-CRISPR-Cas12a detected 6.0 eDNA copies/μL within 35 min. Ecologically rare species were identified in the Three Gorges Reservoir Area (TGRA) using functional distinctiveness and geographical restrictiveness, with seven fish species (9%) classified as potentially ecologically rare including three species in this investigation. RPA-CRISPR/Cas12a-FQ outperformed high-throughput sequencing (HTS) and qPCR in detecting low-abundance eDNA (AUC = 0.883∗∗). A significant linear correlation (R2 = 0.682∗∗) between RPA-CRISPR/Cas12a-FQ and HTS quantification suggests its potential for predicting species abundance and enhancing eDNA-based fish biodiversity monitoring. This study highlights the value of RPA-CRISPR/Cas12a-FQ as a tool for advancing eDNA research and conservation efforts.


Outcomes of double-layer continuous suture hepaticojejunostomy in pancreatoduodenectomy and total pancreatectomy.
This study aims to describe the technique and the results of double-layer continuous suture hepaticojejunostomy (HJ) following pancreatoduodenectomy (PD) and total pancreatectomy (TP). A prospectively maintained database was analyzed retrospectively to identify incidence and severity of biliary leaks (BL) (ISGLS definition), as well as of HJ stenosis (HJS), cholangitis, and need for redo-HJ (in patients with a follow-up ≥3 years) in a consecutive series of 800 procedures (PD = 603; TP = 197). Predictors of biliary complications were also identified. BLs occurred in 5 patients (0.6%), including 2 (0.3%) combined pancreatic and biliary leaks. Rates of HJS, cholangitis, and need for redo-HJ were 6.1%, 5.4%, and 2.0%, respectively. Incidence of BL was 0.6% in open procedures (4/587) and 0.4% in robotic operations (1/213). Incidence of late biliary complications was also equivalent in open and robotic procedures. Occurrence of BL was predicted by ASA IV status and duodenal cancer, HJS by any associated vascular procedure and hepatic duct size < 8 mm, cholangitis by any associated vascular procedure and normal bilirubin/hepatic enzymes, and redo HJ by history of cholecystectomy and neuroendocrine tumor/cancer. Double layer continuous suture HJ is associated with low BL rates, and an acceptable incidence of late complications.


An alternative way to perform diagnostic nasopharyngeal swab for SARS-CoV-2 infection.
On March 11, 2020, WHO has defined the novel coronavirus disease SARS-CoV-2 (COVID-19) outbreak as a pandemic and still today continues to affect much of the world. Among the reasons for the rapid spread of SARS-CoV-2 infection, there is not only the high transmissibility of the virus, but also the role of asymptomatic or minimally symptomatic carriers. Therefore diagnostic testing is central to contain the global pandemic. Up to now real-time reverse transcriptase polymerase chain reaction (RT-PCR)-based molecular assays for detecting SARSCoV-2 in respiratory specimens is the current reference standard for COVID-19 diagnosis. Nasopharyngeal swab is the preferred choice for SARS-CoV-2 testing; however is not always a free of complications procedure. In patients with severe coagulopathies or diseases such as HHT, the risk of nosebleeding may be high. As in all those conditions like advanced stage sinonasal neoplasms or unfavorable anatomical characteristics, the nasopharyngeal swab may not be feasible. This work reports a safe and effective procedure of nasopharyngeal swab collection for COVID-19 testing, through the transoral way, in patients with contraindication to perform it transnasally. The procedure proved feasible and well tolerated. The discomfort for the patient is comparable with the execution of an oropharyngeal swab without exposing him to additional complications. In selected cases, the procedure described represents a valid alternative to nasopharyngeal swab performed transnasally. In particular, it allows reaching the area with the highest diagnostic sensitivity. Moreover it can be performed by Otolaryngology and, with adequate training, also by non-specialist staff.


A survey of pterygium surgery in Thailand 2010.
To survey and investigate the pterygium surgery among Thai ophthalmologists in 2010. Questionnaires were distributed to 930 ophthalmologists who were the member of the Ophthalmological Society and Royal Colleges of Ophthalmologists of Thailand. Data received from 414 respondents were assessed and analyzed The majority of respondents were male (53.1%) while 46.9 % were female. Visual disturbance (57.6%) was the most common indication for surgery. Most of the respondents (41.1%) preferred pterygium excision combined with conjunctival autograft transplantation. Bare scleral technique was the second most common preferential procedure. Recurrence was the main postoperative complication. Although there was a great variation pterygium surgical pattern, excision with conjunctival autograft transplantation was the major preferential practice. Recurrent pterygium was the most common complication.


Improving effects of eplerenone on atrial remodeling induced by chronic intermittent hypoxia in rats.
Atrial fibrillation (AF) is closely associated with the overactivation of the renin-angiotensin-aldosterone system. Large cohort studies and recent meta-analyses have shown that the utilization of mineralocorticoid receptor antagonists has positive effects on the prevention and development of AF. This study aimed to investigate the effects of eplerenone on atrial remodeling in AF model rats and elucidate its intrinsic mechanism. Ninety male Sprague-Dawley rats were randomly divided into the control group, chronic intermittent hypoxia (CIH) group, and CIH-eplerenone intervention (CIH-E) group. Rats in the CIH and CIH-E groups received CIH for 6 weeks, and rats in the CIH-E group were additionally administered eplerenone gavage (10 mg/kg/d). After modeling, the baseline parameters of each group were examined. Histopathology, molecular biology, isolated electrophysiology, and patch clamp experiments were performed after sampling. Compared with the control group, rats in the CIH group showed atrial enlargement, significant aggravated fibrosis, upregulated JAK/STAT3 pathway, shortened effective refractory period (ERP), increased AF inducibility, and decreased peak current density of characteristic voltage-gated ion channels in atrial myocytes. After eplerenone intervention, rats in the CIH-E group had a smaller atrial diameter than those in the CIH group. Furthermore, downregulated JAK/STAT3 pathway, prolonged ERP, decreased AF inducibility, and increased peak current density of characteristic ion channels were also observed in the CIH-E group. CIH induced significant atrial remodeling in rats and eplerenone significantly ameliorated the atrial remodeling caused by CIH. This could be attributed to the downregulation of the JAK/STAT3 pathway and the increase in the characteristic ion current density of atrial myocytes.


Perceived sources and levels of stress, general self-efficacy and coping strategies in preclinical dental students.
Dental education programs are known to be highly stressful and stress can affect general health. The aims were to identify sources of stress among preclinical students and to evaluate their perceived levels of stress, self-efficacy and effective coping strategies in a private dental school. One hundred preclinical students in a Turkish private dental school were surveyed using dental environment stress (DES), perceived stress (PSS), general self-efficacy (G-SES) and brief coping scales (Brief-COPE). Age, gender, history of psychiatric treatment, factors that affected the choice of dentistry, choice rank of dental school, scholarship and income was recorded. 'Exams and grades' followed by 'Fear of failing course or year' were found to be the most stressprovoking factors. The most and the least stressprovoking DES domains were 'Workload' and 'Social stressors', respectively. 'Social stressors' affected male more than female (p < .05). The most and the least common coping strategies were found to be 'Planning', and 'Drug', respectively. Female used 'Instrumental support' more than male (p < .05). Demographic factors had impact on the perceived stress factors and levels, as well as coping strategies. Unlike previous studies establishing high stress levels in dental students, preclinical students displayed moderate level of stress. Clinical dental education might be more responsible for creating stress.


Reproducibility of phalanx osteosonography and relation with forearm peripheral quantitative computed tomography: single finger versus average measurement on the last four fingers.
The aim of this study was to evaluate the in vivo short-term reproducibility of amplitude-dependent speed of sound (AD-SOS) measured at the proximal phalanx, using an Igea DBM Sonic 1200 device, as well as its relationship with bone mineral density of the ultradistal radius, assessed using peripheral quantitative computed tomography (pQCT). In particular, the authors wished to evaluate whether average measurements on the last four fingers, as recommended by the manufacturer, yielded or not more information than measurements on one single finger. For the precision study, the authors carried out phalanx osteosonography ten times once every other day in ten healthy young women. To compare with pQCT of the radius, 37 women referred for screening of osteoporosis (mean age 60 years) were studied. AD-SOS was reported for each finger separately, as well as an average; pQCT (XCT 960 Stratec) yielded trabecular (BMDt); cortical (BMDc); and total (BMDtot) bone mineral densities, as well as the cortical area (Ac). The reproducibility of AD-SOS was significantly higher for the middle finger (mean coefficient of variation (CV) 1.1%) and the index than for the ring and small (mean CV 2.7%) finger. The middle finger consistently showed the best correlations with pQCT variables; the relationships involving BMDc (r = 0.54), BMDtot (r = 0.62) and Ac (r = 0.61) were stronger than that with BMDt (r = 0.34). The authors conclude that phalanx AD-SOS is moderately correlated with BMD of the ultradistal radius--at least when it includes the cortical component--and that reporting AD-SOS for the middle finger--instead of an average value--improves the reproducibility and possibly the relevance of phalanx osteosonography.


Prepubic and thigh abscess after successive placement of two suburethral slings.
We present a case of prepubic and thigh abscess after the placement of two types of suburethral slings in a 65-year-old woman suffering from stress urinary incontinence (SUI). The first surgical procedure (prepubic tension-free vaginal tape) was unsuccessful. Thus, 2 months later, we placed an ObTape sling by transobturator approach. This second procedure was successful. Seven months later, the patient presented with vaginal erosion of the sling with no inflammatory signs. The suburethral portion of the sling was immediately removed and the vagina was sutured. Nine months later, a prepubic abscess occurred and required removal of the prepubic sling, drain placement, and antibiotic therapy. Unfortunately, 9 months later, a thigh abscess occurred. Magnetic resonance imaging (MRI) allowed precise diagnosis and anatomic localization of the thigh abscess. Surgery consisted of opening and draining the abscess and removing the transobturator sling. At 6 months follow-up, no persistent inflammatory sign was observed on MRI, and SUI did not recur.


Glutathione S-transferase genotype is associated with sensitivity to psoralen-ultraviolet A photochemotherapy.
There is marked interpatient variation in responses to psoralen-ultraviolet A (PUVA) photochemotherapy. Identification of molecular biomarkers of PUVA sensitivity may facilitate treatment predictability.The glutathione S-transferases (GSTs) influence cutaneous defence against UV radiation-induced oxidative stress and are therefore candidate biomarkers of PUVA sensitivity. Several human GSTs, including GSTM1 and GSTT1, are polymorphic, and null polymorphisms have been associated with increased UVB erythemal sensitivity and skin cancer risk. PUVA also increases skin cancer risk. To investigate the effect of GST genotype on PUVA sensitivity. We investigated GST genotype in patients starting PUVA (n=111) and the effects of 8-methoxypsoralen (8-MOP) on antioxidant response element (ARE)-regulated gene expression in mammalian cells. Lower minimal phototoxic doses (MPD) (P=0·022) and higher serum 8-MOP concentrations (P=0·052) were seen in GSTM1-null allele homozygotes compared with patients with one or two active alleles. In a subset of patients with psoriasis (n=50), the GSTM1 genotype was not associated with PUVA outcomes, although MPD [hazard ratio (HR) 1·37; 95% confidence interval (CI) for HR 1·15-1·64] and GSTT1-null (HR 2·39; 95% CI for HR 1·31-4·35) and GSTP1b (HR 1·96; 95% CI for HR 1·10-3·51) genotypes were associated with clearance of psoriasis in this patient group. Exposure of mammalian cells to 8-MOP induced gene expression via the ARE, a regulatory sequence in promoters of cytoprotective genes including GSTs, suggesting that these genes may be implicated in 8-MOP metabolism. The polymorphic human GSTs are associated with PUVA sensitivity. Further studies are required to examine the clinical relevance of these preliminary findings.


[The possible role of changes in calcium conduction in the early enhancement of spinal reflex responses after dissection of the sciatic nerve].
Effects of imidazol, 4-aminopyridin and verapamil on evoked monosynaptic responses 5-7 days after cutting of the sciatic nerve have been studied in white rats. Imidazol induced no changes for certain 4-aminopyridin increased and verapamil decreased amplitude of responses on the side of cutting nerve.


TAZ is important for maintenance of the integrity of podocytes.
The podocyte is an important component of the glomerular filtration barrier, and maintenance of the integrity of its highly specified structure and function is critical for normal kidney function. Yes-associated protein (YAP)/transcriptional coactivator with PDZ-binding motif (TAZ) are two crucial effectors of the Hippo signaling pathway, and recent studies have shown that podocyte-specific YAP deletion causes podocyte apoptosis and the development of focal segmental glomerulosclerosis followed by progressive renal failure. In the present study, we investigated a potential role of the YAP paralog TAZ in podocytes. TAZ was found to be constitutively active in podocytes, and mice with podocyte-specific deletion of TAZ (TazpodKO) developed proteinuria starting at 4 wk of age and had increased podocyte apoptosis. Using primary cultured podocytes or immortalized mouse podocytes from Tazflox/flox mice, we found that TAZ is a transcriptional activator for TEAD-dependent expression of synaptopodin, zonula occludens-1, and zonula occludens-2. This is the first study to determine that TAZ plays an important role in the maintenance of the structure and function of podocytes.NEW & NOTEWORTHY Podocytes play an important role in maintaining the integrity of the structure and function of the kidney. We observed that mice with selective deletion of transcriptional coactivator with PDZ-binding motif (TAZ) in podocytes developed proteinuria. TAZ is constitutively active and critical for expression of synaptopodin, zonula occludens-1, and zonula occludens-2 in podocytes. The findings of this study implicate TAZ as an important mediator of podocyte structural integrity and provide further insights into the role of Hippo-Yes-associated protein/TAZ in podocyte biology.


Functional deficits in the optokinetic system of albino rats.
Vestibular nuclear neurons of the horizontal canal system (Vn) of albino rats (Wistar) failed to respond to optokinetic stimulation. Similarly, optokinetic nystagmus (OKN) could not be elicited in these animals. Brown (DA--HAN) rats, however, consistently showed optokinetic responses of Vn and OKN to identical stimuli.


ORLNC1 Suppresses Cell Growth in HER2-Positive Breast Cancer via miRNA-296 Sponging.
Accumulating research has demonstrated that aberrant levels of long noncoding RNAs (LncRNAs) are related to cancer progression. The effects of ORLNC1 in HER2+ breast cancer have yet to be explored. Real-time PCR was used to examine the expression of LncRNA ORLNC1 in HER+ breast cancer. CCK-8, wound healing and cell invasion assays were used to examine the effect of LncRNA ORLNC1 on HER+ breast cancer cells. Luciferase reporter assay was utilized to determine the regulatory relationship between LncRNA ORLNC1 and miR-296. Western blotting was used to measure the expression of PTEN. Xenograft mouse model was used to examine the effect of LncRNA ORLNC1 on tumor progression in vivo. In this study, our findings revealed downregulation of ORLNC1 in HER2+ breast cancer specimens and cell lines. Low levels of ORLNC1 were related to poor prognosis and advanced cancer stage. Using gain- and loss-of-function assays, the ability of these tumor cells to proliferate was found to be inhibited by ORLNC1 in vitro and in vivo. Further analyses revealed that miR-296/PTEN axis is directly targeted by ORLNC1. Consequently, over-expression of miR-296 efficiently abrogated the upregulation of PTEN induced by ORLNC1, suggesting that ORLNC1 positively regulates PTEN expression by competitively binding to miR-296. Our results indicate that lncRNA ORLNC1 acts as a tumor suppressor by regulating the miR-296/PTEN axis in HER2+ breast cancer.


Amniotic fluid testosterone and follicle-stimulating hormone in the determination of fetal sex.
To determine whether hormone analysis could be used for accurate determination of fetal sex, we measured testosterone (T) and follicle-stimulating hormone (FSH) in 130 amniotic fluid samples at midgestation. The mean unconjugated T in amniotic fluid of 73 patients carrying male fetuses was 202 pg. per milliliter (95 per cent confidence limits [CL]: 70 to 580) and all but three had levels higher than 90 pg. per milliliter. The mean amniotic fluid unconjugated T for 49 patients carrying female fetuses of 41 pg. per milliliter (95 per cent CL: 11 TO 125) was fivefold lower than that for the male fetuses and all but three patients carrying female fetuses had amniotic fluid T levels of 90 pg. per milliliter or lower. The mean amniotic fluid FSH of 0.7 ml. U. per milliliter (95 per cent CL: less than 0.5 to 3.4) for subjects with male fetuses was tenfold lower than that for patients with female fetuses. Amniotic fluid FSH levels less than 2.0 ml. U. per milliliter were found in 88 per cent of patients carrying male fetuses and in only one patient with a female fetus, and levels greater than 10 ml. U. per milliliter were found in those with female fetuses only. In eight patients (7 per cent of cases), neither amniotic fluid T nor FSH determinations were indicative of fetal sex. Measurement of unconjugated T and FSH in amniotic fluid may be an adjunct to other methods of determining fetal sex.


Factors affecting soil treatment with the microbially induced carbonate precipitation technique and its optimization.
The microbially induced carbonate precipitation (MICP) technique has been used to increase mechanical strength, reduce permeability, and fix radionuclides of soils, etc. To achieve effective soil cementation by MICP, 3 aspects should be considered: MICP efficiency, bacterium retention (in soils after injections), and precipitation uniformity. Here, experiments and statistical analyses were conducted to understand the parameters affecting the 3 aspects. Moreover, the parameters leading to better performance in these aspects were designed and used to conduct MICP soil cementation with varying the number of injections. The results present that temperature and OD600nm of bacterial suspension are the most important parameters affecting MICP efficiency, followed by reaction time, pH, and concentration of cementation solution, and they are all statistically significant. As these parameters increased, MICP efficiency (ratio of CaCO3 formed to Ca2+ added) first increased quickly and then slowly or decreased. The soil particle size distribution and injection rate affected bacterium retention greatly. Smaller particle sizes, wider particle-size-distribution spans, and slower injection rates are beneficial to bacterium retention. However, higher injection rates favour precipitation uniformity. Finally, the unconfined compressive strength (UCS) of the bio-treated soil can be increased further by increasing the number of injections.


Vitamin-D ameliorates sepsis-induced acute lung injury via augmenting miR-149-5p and downregulating ER stress.
Acute lung injury is a life-threatening medical problem induced by sepsis or endotoxins and may be associated with enhanced Endoplasmic reticulum stress (ER stress). Vitamin-D (Vit-D) possesses an anti-inflammatory effect; however, this specific mechanism on acute lung injury is still unknown. Here we scrutinize the mechanism of Vit-D on Acute lung injury (ALI) models and explored the Vit-D augmented miRNA's role in regulating the ER stress pathway in ALI. Sepsis was induced by CLP, and Endotoxemia was caused by lipopolysaccharide (LPS). We found that Vit-D alleviates pulmonary edema, improves lung histoarchitecture, infiltration of neutrophils, endothelial barrier in mice, and improves ER stress markers Activating Transcription Factor 6 (ATF6) and CHOP (C/EBP Homologous Protein) expression elevated by CLP/LPS induce ALI. Vit-D decreases the nitric oxide production and ATF6 in macrophages induced by LPS. Vit-D augments miR (miR-149-5p) in LPS-induce macrophages, CLP, and LPS-induced ALI models. Vit-D enhanced miRNA-149-5p when overexpressed, inhibited ER-specific ATF6 inflammatory pathway in LPS-stimulated macrophages, and improved histoarchitecture of the lung in LPS/CLP-induced mice models. This vitro and vivo studies demonstrate that Vit-D could improve ALI induced by CLP/LPS. In this regard, miR-149-5p may play a crucial role in vitamin-D inhibiting LPS/CLP induce ALI. The mechanism might be an association of increased miR-149-5p and its regulated gene target ATF6, and downstream CHOP proteins were suppressed. Thus, these findings demonstrate that the anti-inflammatory effect of Vit-D is achieved by augmentation of miRNA-149-5p expression, which may be a key physiologic mediator in the prevention and treatment of ALI.


Direct observation and temperature control of the surface Dirac gap in a topological crystalline insulator.
Since the advent of topological insulators hosting Dirac surface states, efforts have been made to gap these states in a controllable way. A new route to accomplish this was opened up by the discovery of topological crystalline insulators where the topological states are protected by crystal symmetries and thus prone to gap formation by structural changes of the lattice. Here we show a temperature-driven gap opening in Dirac surface states within the topological crystalline insulator phase in (Pb,Sn)Se. By using angle-resolved photoelectron spectroscopy, the gap formation and mass acquisition is studied as a function of composition and temperature. The resulting observations lead to the addition of a temperature- and composition-dependent boundary between massless and massive Dirac states in the topological phase diagram for (Pb,Sn)Se (001). Overall, our results experimentally establish the possibility to tune between massless and massive topological states on the surface of a topological system.


[Research into complementary medicine--an account after 10 years].
For ten years now, intensive research into complementary medicine has been undertaken in Exeter, UK. Aimed at providing an interim account of our activities, this paper presents several examples of our results. Although some progress has been made, this field continues to receive too little attention. The future of complementary medicine will depend on whether its modalities can be shown to generate more good than harm for the patient.


Post Traumatic Stress Disorder and Substance Use Disorder as Two Pathologies Affecting Memory Reactivation: Implications for New Therapeutic Approaches.
In the present review, we provide evidence indicating that although post traumatic stress disorder (PTSD) and substance use disorder (SUD) are two distinct pathologies with very different impacts on people affected by these chronic illnesses, they share numerous common characteristics, present high rates of co-morbidity, and may result from common physiological dysfunctions. We propose that these pathologies result from hyper reactivity to reminders, and thus should be considered as two disorders of memory, treated as such. We review the different possibilities to intervene on pathological memories such as extinction therapy and reconsolidation blockade. We also introduce new therapeutic avenues directly indicate by our recent proposal to replace the consolidation/reconsolidation hypothesis by the integration concept. State dependency and emotional remodeling are two innovative treatments that have already provided encouraging results. In summary, this review shows that the discovery of reactivation-dependent memory malleability has open new therapeutic avenues based on the reprocessing of pathological memories, which constitute promising approaches to treat PTSD and SUD.


Interfering HMGB3 release from cancer-associated fibroblasts by miR-200b represses chemoresistance and epithelial-mesenchymal transition of gastric cancer cells.
Cancer-associated fibroblasts (CAFs) are vital components of gastric cancer (GC) microenvironments, which impact the aggressive characteristics of GC cells. The objective of this study is to evaluate the influence of High Mobility Group Box (HMGB) on CAF-related GC. The tissues of 10 GC patients who underwent surgery the Sanya Central Hospital of Hainan Province from July 2018 to July 2019 were collected for the clinical study. Moreover, the GC cell lines, including MGC-803, AGS, and SGC-7901, were used in vitro experiment. We investigated the molecular mechanism of the miR-200b/HMGB3 axis in affecting the chemoresistance and epithelial-mesenchymal transition (EMT) of GC cells induced by CAFs. Cell transfection, Cell Counting Kit-8 (CCK-8), Transwell assay, western blot, enzyme-linked immunosorbent assay (ELISA), and other experiments were employed. We found that miR-200b was down-regulated, yet HMGB3 was up-regulated in CAF-related GC. The CAFs markedly promoted cisplatin (CDDP) resistance, proliferation, invasion, migration, and EMT of GC cells. Gain-assay of miR-200b demonstrated that miR-200b inhibited the HMGB3 release from CAFs. In-vivo experiments confirmed that the growth and EMT of GC cells co-cultured with CAF-miR-200b were significantly reduced. Furthermore, CAFs enhanced the activation of ERK, JNK, and the Wnt/β-catenin pathways, and those pathways, as well as the malignant behaviors of GC cells, were obviously attenuated by miR-200b or HMGB3 silencing. Collectively, HMGB3 derived from CAFs is negatively regulated by miR-200b and promotes the malignant behaviors of GC cells.


End-of-life medical decision making in general practice in New Zealand--13 years on.
The aim of this study was to explore medical decision-making practices at the end-of-life made by GPs (MDEL) in New Zealand and to identify changes in practice with a previous study published in 2004. A postal questionnaire was sent to 3,420 GPs in New Zealand in May 2013. Anonymous phone interviews were also undertaken. Analysis of the questionnaire was done on IBM SPSS Statistics 21. There was a 21% response rate from two mail outs. Of the 650 GPs who responded, 547 had contact with a patient prior to death and had the potential to make a MDEL. Of these, 359 (65.6%) reported making a MDEL. Of the 359 GPs who reported making a MDEL, 16 (4.5%) attributed death to a drug that had been prescribed, supplied or administered explicitly for the purpose of hastening the patient's death. The alleged involvement of nurses in practices that intentionally hasten death is high. Our study shows that some GPs have explicitly assisted their patients to die, that nurses are allegedly involved, and there is a tendency towards more discussion with patients about MDEL.


Electrical activity in cerebellar cultures determines Purkinje cell dendritic growth patterns.
In primary dissociated cultures of mouse cerebellum a number of Purkinje cell-specific marker proteins and characteristic ionic currents appear at the appropriate developmental time. During the first week after plating, Purkinje cell dendrites elongate, but as electrical activity emerges the dendrites stop growing and branch. If endogenous electrical activity is inhibited by chronic tetrodotoxin or high magnesium treatment, dendrites continue to elongate, as if they were still immature. At the time that branching begins, intracellular calcium levels become sensitive to tetrodotoxin, suggesting that this cation may be involved in dendrite growth. Even apparently mature Purkinje cells alter their dendritic growth in response to changes in activity, suggesting long-term plasticity.


Effect of technique on postoperative perineal wound infections in abdominoperineal resection.
Perineal wound infection (PWI) after abdominoperineal resection causes a burden for patients and health systems. We sought to determine the effect of patient positioning on the incidence of postoperative surgical site infection. We conducted a retrospective cohort study of patients who underwent APR in our hospital system over a 10-year period. Univariate analysis was performed to identify characteristics associated with position and PWI. A logistic model was developed to assess the relationship of position and PWI, with adjustment for confounders. Patient characteristics were similar for the prone and lithotomy positions. Operative time was less for the prone than for the lithotomy position. The prone position was associated with a reduced risk of PWI. After adjustment for potential confounders, the prone position remained significantly associated with a reduction in PWI. Positioning patients in the prone position results in a lower occurrence of postoperative PWI and shorter operative time. We advocate this technique for most indications of APR.


Open-gate mutants of the mammalian proteasome show enhanced ubiquitin-conjugate degradation.
When in the closed form, the substrate translocation channel of the proteasome core particle (CP) is blocked by the convergent N termini of α-subunits. To probe the role of channel gating in mammalian proteasomes, we deleted the N-terminal tail of α3; the resulting α3ΔN proteasomes are intact but hyperactive in the hydrolysis of fluorogenic peptide substrates and the degradation of polyubiquitinated proteins. Cells expressing the hyperactive proteasomes show markedly elevated degradation of many established proteasome substrates and resistance to oxidative stress. Multiplexed quantitative proteomics revealed ∼ 200 proteins with reduced levels in the mutant cells. Potentially toxic proteins such as tau exhibit reduced accumulation and aggregate formation. These data demonstrate that the CP gate is a key negative regulator of proteasome function in mammals, and that opening the CP gate may be an effective strategy to increase proteasome activity and reduce levels of toxic proteins in cells.


Serial antenatal monitoring compared with labor induction in post-term pregnancies.
In view of the increased risk of obstetric and perinatal complications in post-term pregnancy, and the lack of consensus regarding clinical routines for fetal surveillance and labor induction, the aim of this prospective controlled study was to compare obstetric and perinatal outcome after serial monitoring until 43 weeks of gestation with that after labor induction at 42 gestational weeks. A study group of 193 gravidae scheduled for serial monitoring until 43 weeks of gestation was compared with a control group of 205 gravidae admitted for induction of labor at 42 weeks. A third, high-risk, group comprised gravidae (from either of the foregoing groups) who had to be admitted for emergency induction of labor owing to increased fetal risk (i.e., the presence of oligohydramnios or a small-for-gestational-age fetus). The frequency of labor induction was significantly lower in the study group than among controls (p < 0.001), but the two groups did not differ in obstetric or perinatal outcome. As compared with these two low-risk groups, the high-risk group was characterized by significantly higher frequencies of instrumental delivery (p < 0.01), operative delivery for fetal distress (p < 0.001) and infants requiring neonatal intensive care (p < 0.001). As the wait-and-see policy with serial monitoring resulted in a lower rate of labor induction, but not in a lower rate of instrumental delivery or perinatal complication, medically the two routines would appear to be comparable. However, an individual approach with intensified fetal surveillance is to be recommended, as it is vital to identify post-term pregnancies where the fetus is at increased risk. The use of such new techniques as umbilical artery flow velocimetry would no doubt improve the management of high-risk post-term pregnancies.


Establishing a correct diagnosis of vulvovaginal infection.
Vulvovaginitis is a common problem and a prime reason for physician consultation. The organism most frequently responsible for vulvovaginal infection is Candida albicans, and in a large majority of cases identification of the causative organism and diagnosis are easy to establish. Recurrent or persistent infection, however, presents a perplexing diagnostic problem that usually can be solved with the use of appropriate supportive laboratory tests and awareness of the distinguishing features of the possible etiologic agents. Problems in diagnosis or complications in treatment are usually due to concurrent infection by two or more organisms or to treatment without proper identification of the infectious agents.


A Method to Map Gene Essentiality of Human Pluripotent Stem Cells by Genome-Scale CRISPR Screens with Inducible Cas9.
Human pluripotent stem cells (hPSCs) have the capacity for self-renewal and differentiation into most cell types and, in contrast to widely used cell lines, are karyotypically normal and non-transformed. Hence, hPSCs are considered the gold-standard system for modelling diseases, especially in the field of regenerative medicine. Despite widespread research use of hPSCs and induced pluripotent stem cells (iPSCs), the systematic understanding of pluripotency and lineage differentiation mechanisms are still incomplete. Before tackling the complexities of lineage differentiation with genetic screens, it is critical to catalogue the general genetic requirements for cell fitness and proliferation in the pluripotent state and assess their plasticity under commonly used culture conditions.We describe a method to map essential genetic determinants of hPSC fitness and pluripotency, herein defined as cell reproduction, by genome-scale loss-of-function CRISPR screens in an inducible S. pyogenes Cas9 H1 hPSC line. To address questions of context-dependent gene essentiality, we include protocols for screening hPSCs cultured on feeder cells and laminin, two commonly used growth substrates. This method establishes parameters for genome-wide screens in hPSCs, making human stem cells amenable for functional genomics approaches to facilitate investigation of hPSC biology.


Amlodipine reduces myocardial ischaemia during exercise without compromising left ventricular function in patients with silent ischaemia: a randomised, double-blind, placebo-controlled study.
Left ventricular systolic function is reduced during episodes of silent ischaemia in patients with coronary artery disease (CAD). In most normal subjects left ventricular ejection fraction (LVEF) increases at least 5% during exercise whereas LVEF often remains unchanged or decreases in patients with CAD. The anti-ischaemic effect of calcium antagonists is well documented including a capability to reduce exercise-induced electrocardiographic ST-depressions, whereas the effect of these drugs on LV volume changes during exercise in patients with silent ischaemia is unknown. The aim of this study was to evaluate the effect of amlodipine on rest and exercise LVEF in patients with silent ischaemia. Twenty-one patients completed a double-blind placebo-controlled cross-over study. Conventional exercise test and radionuclide cardiographies during exercise were used for determining haemodynamic parameters. Exercise-induced electrocardiographic ST-depressions were reduced in 83% of the patients having ST-deviations during placebo even though 10 patients were already treated with a beta-blocker. Amlodipine did not affect left ventricular systolic function compared to placebo, neither at rest nor during exercise. The results indicated that amlodipine is a safe anti-ischaemic drug in patients with silent ischaemia concerning cardiac function.


Time-resolved X-ray crystallographic study of the conformational change in Ha-Ras p21 protein on GTP hydrolysis.
Crystals of Ha-Ras p21 with caged GTP at the active site have been used to investigate the conformational changes of p21 on GTP hydrolysis. The structure of the short-lived p21.GTP complex was determined by Laue diffraction methods. After GTP hydrolysis, substantial structural changes occur in the parts of the molecule implicated in the interaction with GTPase-activating protein. The trigger for this process seems to be a change in coordination of the active-site Mg2+ ion as a result of loss of the gamma-phosphate of GTP.


The nature of extra-chromosomal maintenance of transforming plasmids in the filamentous basidiomycete Phanerochaete chrysosporium.
The nature of extra-chromosomal maintenance of the transforming plasmid p12-6 in Phanerochaete chrysosporium was studied. Our results indicate that the plasmid is maintained in the fungal transformants extra-chromosomally as part of a larger endogenous plasmid (designated pME) of P. chrysosporium. Using the total DNA of p12-6 fungal transformants, p12-6, as well as a larger plasmid, p511, were recovered in recA- E. coli strains while only p12-6 was recovered in recA+ E. coli strains. The results also showed that the cytosine methylation system has no apparent effect on the strain-dependent recovery of p12-6 and p511 in E. coli from the total DNA of fungal transformants.


The interaction of alkynyl carboxylates with serine enzymes. A potent new class of serine enzyme inhibitors.
The recently reported alkynyl esters, propynyl benzoate and propynyl p-methoxybenzoate, were found to interact with a variety of serine enzymes. alpha-Chymotrypsin was inhibited very rapidly by an equivalent amount of the esters. Trypsin, elastase and pronase were also inhibited by the esters. On the other hand, liver esterase started to hydrolyze the alkynyl esters rapidly, but the enzyme became inhibited during the course of reaction. The inhibited enzymes exhibited slow reactivation which could be considerably enhanced by hydroxylamine.


Effect of sublingual immunotherapy with grass monomeric allergoid on allergen-specific T-cell proliferation and interleukin 10 production.
Sublingual immunotherapy (SLIT) is safe and efficacious in the treatment of patients with allergic rhinitis. Although favorable clinical effects have been observed with controlled trials as early as a few months since the beginning of treatment, few biological changes induced by SLIT have been demonstrated. To investigate in grass-allergic patients the effect of a 2-month SLIT regimen, administered with a simplified protocol without up-dosing, on proliferation and production of cytokines characteristic of the regulatory T-cell phenotype (interleukin 10 [IL-10] and transforming growth factor beta [TGF-beta]) by allergen-specific T cells. Patients were recruited to the study in January 2006. SLIT was performed by self-administration and was continued for 60 days from February to April 2006. Eleven grass pollen-allergic patients with seasonal rhinitis were treated daily before the pollen season for 2 months with a modified allergen (monomeric allergoid) derived from a 3-grass pollen extract. Allergen-specific proliferation and production of IL-10 and TGF-beta were measured on peripheral blood mononuclear cells at baseline and treatment end. Tetanus toxoid served as the control antigen. After SLIT, allergen-specific (P = .002) but not tetanus toxoid-specific proliferation decreased, whereas IL-10 transcription increased (P < .001). TGB-beta transcription was also increased after treatment, although not statistically significantly (P = .06). Changes in proliferation to allergen and in IL-10 transcription were correlated (r = -0.82, P = .003). A short-term course of SLIT with modified allergen in grass-allergic patients is associated with the reduction of allergen-specific proliferation and with the up-regulation of the IL-10 regulatory cytokine.


Phosotynthesis in hemiepiphytic species of Clusia and Ficus.
Hemiepiphytic species in the genera Clusia and Ficus were investigated to study their mode of photosynthetic metabolism when growing under natural conditions. Despite growing sympatrically in many areas and having the same growth habit, some Clusia species show Crassulacean acid metabolism (CAM) whereas all species of Ficus investigated are C3. This conclusion is based on diurnal CO2 fixation patterns, diurnal stomatal conductances, diurnal titratable acidity fluctuations, and δ13C isotope ratios. Clusia minor, growing in the savannas adjacent to Barinas, Venezuela, shows all aspects of Crassulacean acid metabolism (CAM) on the basis of nocturnal gas exchange, stomatal conductance, total titratable acidity, and carbon isotope composition when measured during the dry season (February 1986). During the wet season (June 1986), the plants shifted to C3-type gas exchange with all CO2 uptake occurring during the daylight hours. The carbon isotope composition of new growth was-28 to-29‰ typical of C3 plants.


Defect Engineering Enhances the Charge Separation of CeO2 Nanorods toward Photocatalytic Methyl Blue Oxidation.
Defect-rich photocatalytic materials with excellent charge transfer properties are very popular. Herein, Sm-doped CeO2 nanorods were annealed in a N2 atmosphere to obtain the defective Sm-doped CeO2 photocatalysts (Vo-Sm-CeO2). The morphology and structure of Vo-Sm-CeO2 were systematically characterized. The Vo-Sm-CeO2 nanorods demonstrated an excellent photodegradation performance of methyl blue under visible light irradiation compared to CeO2 nanorods and Sm-CeO2. Reactive oxygen species including OH, ·O2-, and h+ were confirmed to play a pivotal role in the removal of pollutants via electron spin resonance spectroscopy. Doping Sm enhances the conductivity of CeO2 nanorods, benefiting photogenerated electrons being removed from the surface reactive sites, resulting in the superior performance.


[Measurement of spinal cord blood flow in rabbits: central gray matter flow and CO2 reactivity (author's transl)].
Spinal cord blood flow (SCBF) was measured in 20 rabbits anesthetized with sodium pentobarbital. The platinum electrodes (0.3 mm in diameter) were inserted into the central gray matter of the thoracic spinal cord (Th8-10). In all animals, blood pressure and pAO2 remained constantly in the normal range. The pACO2 was changed by ventilation. Blood gases were checked both before and after each spinal cord blood flow measurement. The results are as follows. 1. Seventy-three percent of the clearances recorded from the gray matter were monoexponential and in the white matter almost all were monoexponential. 2. The mean values of gray matter SCBF of all animals was 38.3 +/- 1.85 ml/100 g/min (SE) at normo-capnea and the white matter was 19.5 +/- 1.33 ml/100 g/min. 3. An almost linear relationship exists between the pACO2 and SCBF. The values were 0.62 ml/100 g/min/torr in the gray matter and 0.38 ml/100 g/min/torr in the white matter.


Evolutionary studies of malaria vectors.
The rationales given for studies of the population genetics of vectors are usually: (1) to predict the spread of genes, such as genes conferring insecticide resistance or possibly refractoriness to parasites and (2) to reveal novel insights into the epidemiology and transmission of vector-borne disease. The successful genetic transformation of mosquitoes has highlighted the need for a critical assessment of the rapidly accumulating body of data on the population genetics of malaria vectors. This article assesses how successful molecular genetic techniques have been in revealing new population patterns.


Assessment of structural lesions, synovitis and bone marrow lesions in erosive hand osteoarthritis on MRI (0.3T) compared to the radiographic anatomical Verbruggen-Veys score.
To evaluate prevalence of structural lesions, synovitis and bone marrow lesions (BMLs) on MRI performed with a 0.3T imaging system in patients with erosive hand osteoarthritis (EHOA) and to compare them to the anatomic radiographic Verbruggen-Veys score (VV). For this Cross-sectional study, fifty-five EHOA patients were studied with 0.3T contrast-enhanced MRI and radiography (RX) of their dominant hand. Structural lesions were scored according to the OMERACT Hand Osteoarthritis MRI Scoring System as follows: osteophytes and erosions were graded from 0 to 3. On joint destruction lesion synovitis and BMLs were graded from 0 to 1. And on MRI, we evaluated the presence of several structural features: N: normal, O: osteophytic lesions, E: erosive lesions, E/O: osteophytic and erosive lesions and D: joint destruction. RX was scored according to the VV system. Relations between MRI features and VV stages were analysed. MRI identified more structural lesions than RX (77.3% versus 74.8%) and particularly more erosive lesions (E or E/O) than VV Phase E (33.5% versus 20.2%). E/O and D were mostly found on MRI. Synovitis and BMLs were significantly associated with E/O and D with the following odds ratios (ORs): 8.4 (95% CI 1.8-13.6); OR: 13.7 (95% CI 2.9-21.0); OR: 15.7 (95% CI 3.2-23.5); OR: 38.5 (95% CI 9.5-57.0), respectively. MRI 0.3T appears completely relevant for EHOA lesion analysis. First, MRI shows more erosive lesions than RX in EHOA; second, it allows for the analysis of synovitis and BMLs to be associated with more specific structural MRI features (E/O and D).


RNA interference and plant parasitic nematodes.
RNA interference (RNAi) has recently been demonstrated in plant parasitic nematodes. It is a potentially powerful investigative tool for the genome-wide identification of gene function that should help improve our understanding of plant parasitic nematodes. RNAi should help identify gene and, hence, protein targets for nematode control strategies. Prospects for novel resistance depend on the plant generating an effective form of double-stranded RNA in the absence of an endogenous target gene without detriment to itself. These RNA molecules must then become available to the nematode and be capable of ingestion via its feeding tube. If these requirements can be met, crop resistance could be achieved by a plant delivering a dsRNA that targets a nematode gene and induces a lethal or highly damaging RNAi effect on the parasite.


Are there gender-specific aspects of gastric banding? Data analysis from the quality assurance study of the surgical treatment of obesity in Germany.
Since 1 January 2005, the situation of bariatric surgery has been examined in Germany. All data are registered prospectively in cooperation with the Institute of Quality Assurance in Surgery at the Otto-von-Guericke University Magdeburg. Data collection on the results of gastric banding procedures was started in 2005, and the data are registered in an online database. Follow-up data were collected once a year. Participation in the quality assurance study is voluntary. Since 2005, 3,453 gastric banding procedures have been performed at 88 hospitals. The mean age of patients was 40.7 years, and the mean body mass index (BMI) was 45.2 kg/m2. BMI and comorbidities are significantly higher in male patients. Regarding gender-specific aspects, there are no significant differences in the perioperative complication rates. The amelioration rate of comorbidities in male patients is lower than in female patients. Gastric banding in Germany is generally performed in patients with a BMI below 45 kg/m2. The perioperative complication rate is low. Data from the nationwide survey of the German Bariatric Surgery Registry show significant differences in preoperative comorbidities and their amelioration between male and female patients. There is a need for further evaluation of gender-specific aspects of gastric banding procedures to optimize patient selection, reduce specific postoperative complications, and achieve long-term effects on weight loss and remission of comorbidities.


[Lymphangiography in ovarian cancer].
Lymphangiography (LAG) and retroperitoneal lymphadenectomy were performed in 30 patients with ovarian cancer from May 1985 to Oct. 1986. The results showed that preoperative radiologic-postoperative histologic correlation was 83.3%. There was no false negativity in lymphographic diagnosis of the pelvic node metastases but two false negatives in the para-aortic node. The single most reliable criterion for LAG diagnosis of metastases was a filling-defect in the nodes. The value of LAG as an aid in staging and planning therapy was discussed.


Sodium renal imaging in mice at high magnetic fields.
This work presents the first sodium MRI functional renal study on a mouse model. The tissue sodium concentration was monitored during induced diuresis with furosemide. By using density-weighted chemical shift imaging (DWCSI) at high field strength a temporal resolution of less than 5 min for three dimensional (3D) data sets with high spatial resolution was achieved. A maximum increase of 20% in the cortex and a decrease of 45% of the original signal strength in the medulla were observed. These findings correspond well with experiments conducted on much larger rodent models.


Malignant lymphoma of the parotid gland.
A case of malignant lymphoma of the parotid gland was described. A 15-year-old male developed a mass which was a firm and non-tender. The patient underwent a superficial parotidectomy with preservation of the facial nerve. The tumor was a grey, soft mass, 3 X 4 X 4 cm in size. On microscopic examination, the tumor was intraglandular lymph node with invasion of salivary gland tissue. The tumor cells were seen between acini and ducts. A diagnosis of lymphosarcoma, prolymphocytic, nodular type was made according to the WHO's classification system and the patient was refered for radiation therapy. Further investigations, including radio-isotope scanning of liver, spleen and bone and a biopsy of bone marrow revealed no sign of the disease. The patient was treated with 5380R of cobalt irradiation and in follow-up of a one year's duration there was no recurrence. Our case fulfilled the criteria which was represented by Hyman and Wolff and we reviewed the literature of this condition.


Effect of a moderate electric field on the salting of Atlantic Salmon (Salmo salar): An experimental study and phenomenological understanding.
Salting is one of the oldest methods of preserving food. The main limitation of salting is its extended processing time due to slow salt diffusion. A moderate electric field (MEF) can improve the mass transfer rate through electroporation. Regularly, mass transfer processes are modeled with Fick's second law. However, due to the anisotropic nature of food microstructures, it might be more appropriate to use an anomalous model. The main objective of this study was to search for a phenomenological explanation for salt and water diffusion in the salmon brining process coupled with MEF. Salmon fillets were cut into finite cylinders (0.025 × 0.025 m) and brined in two salt concentrations (6 and 24% w/w NaCl) at 6 °C for 20 h. MEFs were applied in the range of 0 to 2 V/cm. The salt and water contents of the salmon were measured during the process. Fick's second law and anomalous model based on fractional calculus were used to describe the diffusion phenomena. The results showed that an MEF tended to reduce the brining processing time and increase the salt content of salmon. This effect is predominantly due to an increase in the equilibrium salt concentration in the salmon tissue. Mathematical analysis shows that the anomalous diffusion model is more suitable for representing the brining process, exhibiting superdiffusion behavior (α > 1). An MEF accelerates the salt mass transfer into salmon tissue even at lower temperatures, significantly reducing the processing time. In addition, the diffusion process can be characterized with an anomalous model.


Heregulin activation of extracellular acidification in mammary carcinoma cells is associated with expression of HER2 and HER3.
HER2, the erbB-2/neu proto-oncogene product, is a 185-kDa transmembrane glycoprotein related to the epidermal growth factor receptor. Overexpression of HER2 was reported in several human adenocarcinomas, including mammary and ovarian carcinomas. A family of glycoproteins, the heregulin/neu differentiation factors, was characterized and implicated as the ligands for HER2. Recently, it has been shown that HER2 alone is not sufficient to reconstitute high affinity heregulin receptors and that HER3 or HER4 may be the required components of the heregulin receptors on mammary carcinoma cells (Sliwkowski, M.X., Schaefer, G., Akita, R.W., Lofgren, J.A., Fitzpatrick, V.D., Nuijens, A., Fendly, B.M., Cerione, R.A., Vandlen, R.L., and Carraway, K.L., III (1994) J. Biol. Chem. 269, 14661-14665; Plowman, G.D., Green, J.M., Culouscou, J.-M., Carlton, G.W., Rothwell, V.M., and Buckley, W. (1993) Nature 366, 473-475). Using the Cytosensor to measure the extracellular acidification rate, we have examined the effects of recombinant human heregulin-alpha on three mammary carcinoma cell lines expressing HER2 (MDA-MB-453, SK-BR-3, and MCF-7), an ovarian carcinoma cell line expressing HER2 (SK-OV-3), and CHO-K1 and 293-EBNA cells stably transfected with HER2. By reverse transcription polymerase chain reaction and Western blotting, we found that the breast cells also express HER3 and that the ovarian line co-expresses the HER4 message. A dramatic increase in the acidification rate was observed for the mammary carcinoma cells co-expressing high levels of HER2 and HER3. In contrast, the ovarian cells expressing high levels of HER2 and low levels of HER4 or CHO-K1 and 293-EBNA cells expressing HER2 alone were not responsive to heregulin. When these same transfected cells were exposed to monoclonal anti-HER2 antibody followed by anti-IgG to cause aggregation of the HER2 molecules, an increase in the acidification rate was observed, indicating coupling of transfected HER2 to the signal transduction pathway. Transfection of HER2 into MCF-7 cells, on the other hand, gave 4-fold enhanced acidification responses. These data, together with the previously reported high affinity heregulin binding and activation of tyrosine phosphorylation in HER2 and HER3 co-transfected cells support the role of HER2 and HER3 as components of the heregulin receptor in breast cells.


Solid phase synthesis of peptide-selenoesters.
The synthesis of proteins by native chemical ligation greatly enhances the application of chemistry to complex molecules such as proteins. The essential building blocks for this approach traditionally have been peptide-thioester segments that are linked chemoselectively in consecutive reactions. By using peptide selenoesters instead of thioesters, the ligation rate can be significantly accelerated permitting couplings at difficult sites and potentially enabling new ligation strategies. To facilitate the routine synthesis of selenoester peptides, a general and straightforward procedure has been developed that generates a suitably functionalized resin from which the desired selenoester peptide can be readily synthesized. This simple approach utilizes readily available and cheap chemical agents and enables production of peptide selenoesters of excellent quality in short time and with high recovery. In addition, the stability of peptide selenoesters was examined under different native chemical ligation conditions and compared to thioesters. Selenoesters are slightly more reactive and more susceptible to hydrolysis and aminolysis than thioesters but sufficiently stable under mildly acidic conditions (pH 6.5). Under these conditions, rapid selenoester-mediated ligation is kinetically favoured.


Identification of differentially expressed cDNA transcripts from a rat odontoblast cell line.
Odontoblasts and osteoblasts are two among the myriads of cell types present in the craniofacial complex. Both have a common ectomesenchymal origin and secrete macromolecules that are necessary for the formation of dentin and alveolar bone via matrix-mediated mechanisms. The mineralized matrices of bone and dentin differ in morphology and function but several mineral associated proteins, formerly thought to be tissue specific, have been found to be common in both tissues. To decipher the complex molecular mechanisms involved in mineralized dentin formation, the suppressive subtraction hybridization (SSH) approach has been used to identify the genes expressed by polarized odontoblasts. Employing SSH, 187 cDNA clones were identified from the subtracted cDNA library. Many of these genes have not been previously reported to be expressed by terminally differentiated odontoblasts. Genes were classified into seven groups based on the predicted function of the encoded proteins: extracellular matrix; cytoskeletal components, molecules involved in adhesion and cell-cell interaction; metabolic enzymes, transporters, ion channels; protein processing, protein transport and protein folding molecules; nuclear proteins (transcription factors, DNA processing enzymes); signaling molecules and genes of yet unknown function. Northern blot and in situ hybridization analysis performed for five putative novel genes and one new isoform of amelogenin revealed differential expression levels in the osteoblasts, ameloblasts and the odontoblasts of the developing rat molars. Some of the known genes isolated from this enriched pool were the cleavage products of dentin sialophosphoprotein (DSPP) namely, phosphophoryn (PP) and dentin sialoprotein (DSP). Interestingly amelogenin, ameloblastin and enamelin were also expressed in the odontoblasts during dentin formation.


Spatial relationship between heads of dimeric Ncd in the presence of nucleotides and microtubules.
Kinesins are molecular motors that produce mechanical work at the expense of ATP hydrolysis. Here, we studied Ncd (non-claret disjunctional), a (-)-end-directed member of this superfamily. To gain insight into the mechanism by which Ncd generates force and movement, we measured distances between the heads in dimeric Ncd-250-700 using fluorescence resonance energy transfer (FRET). About 5% of Ncd heads were labeled with 1,5-IAEDANS (donor), and the remaining thiol groups were modified with QSY35-iodoacetamide (acceptor). Several lines of experimental evidence suggest that the probes were conjugated to Cys-670 in each head of the dimer. The measured donor-acceptor distance was about 35 A. Nucleotides (ADP, ATP, and AMP-PNP) in the presence and absence of microtubules had only small effects on the interhead distances. Similar results were obtained for bidirectional Ncd mutant in which Asn-340 was replaced by a lysine. The results argue against models of Ncd movement in which the heads undergo large spatial rearrangements during mechanochemical cycle and suggest Gly-347 as a possible pivot point for the head rotation.


NPI-031G (puerarin) reduces anxiogenic effects of alcohol withdrawal or benzodiazepine inverse or 5-HT2C agonists.
Because extracts of kudzu have been used as a hangover remedy in China for many centuries, we tested the ability of NPI-031G (puerarin), an isoflavone isolated from kudzu, to counteract anxiogenic effects associated with withdrawal from chronic alcohol exposure. NPI-O31G (50 and 150 mg/kg ip) significantly increased the social interaction and locomotor activity reduced by withdrawal from 17 days of alcohol (7%) diet. The effects of NPI-031G resembled those of the benzodiazepine antagonist, flumazenil (5 mg/kg), and the 5-HT(2C) antagonist, SB 242084 (1 mg/kg). In a separate study, control rats were pretreated with NPI-031G (30 min) and then given the anxiogenic compounds DMCM, a benzodiazepine inverse agonist, or Ro 600175, a 5-HT(2C) agonist. NPI-031G significantly counteracted the reduction in social interaction induced by either compound. To identify a potential mechanism of action of NPI-031G, synaptoneurosomes were isolated from the cerebral cortex of untreated rats and chloride uptake assays were carried out. NPI-031G did not have any effect on the stimulation of chloride uptake by muscimol, a GABA(A) agonist. However, it reduced the potentiation of muscimol-stimulated chloride uptake by flunitrazepam, a benzodiazepine agonist, at a concentration of 100 microM. A reduction in [3H]flunitrazepam binding was also seen at this concentration. These findings are consistent with NPI-031G being a weak benzodiazepine site antagonist.


Skull deformity in a herring gull chick (Larus argentatus).
A skull deformity resulting in death of a herring gull chick (Larus argentatus) is described in detail. The bones of the skull and upper jaw were twisted, asymmetrical and of unusual size or absent. The lower jaw had an almost "spoon-like" external appearance and lacked normal articular surfaces.


Peroxiredoxin I is a ROS/p38 MAPK-dependent inducible antioxidant that regulates NF-κB-mediated iNOS induction and microglial activation.
Reactive oxygen species (ROS) function as modulators of pro-inflammatory processes in microglia-associated neurodegenerative diseases. However, little is known about the involvement of specific antioxidants in regulating the microglial redox status. Here, we demonstrated that peroxiredoxin (Prx) I activity was induced by lipopolysaccharide (LPS), but not paraquat and hydrogen peroxide, through activation of the ROS/p38 MAPK signal pathway, and participated in alleviating the microglial activation and generation of nitric oxide (NO). Interestingly, a null mutation of Prx I accelerated NF-κB-mediated iNOS induction and subsequent NO secretion in LPS-stimulated microglia. Furthermore, F4/80 expression as microglial activation marker was notably up-regulated in primary cultures of microglia, hippocampal sections, and cerebral cortex of 15-month-old Prx I(-/-) mouse. Taken together, the results of our study indicated that Prx I is an antioxidant that is up-regulated in a ROS/p38 MAPK-dependent manner and governs the progression of neuroinflammation by suppressing microglial activation. In addition, Prx I deficiency increased the nuclear translocation of NF-κB mediated-iNOS induction as pro-inflammatory mediators. The findings of our work suggest possible strategies for developing novel therapies to treat inflammation-associated degenerative neurological diseases by targeting the induction of Prx I in microglial cells.


Anesthetic management of a patient with Weaver syndrome undergoing emergency evacuation of extra-dural hematoma: A case report and review of the literature.
Weaver syndrome is a rare disorder of unknown etiology characterized by skeletal overgrowth, distinctive craniofacial and digital abnormalities and advanced bone age. In general, craniofacial abnormalities that cause difficulty with tracheal intubation may improve, worsen, or remain unchanged as craniofacial structures mature. Furthermore, there is an estimated risk in these children of ≤1.09% of rhabdomyolysis or malignant hyperpyrexia. We report a case of a boy with Weaver syndrome who underwent emergency evacuation of extra-dural hematoma under general anesthesia.


Development and validation of the patient and clinician sedation satisfaction index for colonoscopy and upper endoscopy.
Recent increases in gastrointestinal endoscopic procedures and sedation options show a need for better sedation evaluation. This article describes the development and validation of 2 instruments: the Patient Satisfaction with Sedation Instrument (PSSI) and the Clinician Satisfaction with Sedation Instrument (CSSI) for assessing satisfaction in patients undergoing outpatient upper endoscopy and colonoscopy. A total of 118 patients who underwent outpatient colonoscopy or esophagogastroduodenoscopy and 22 physicians were recruited across 5 US gastroenterology practices. Physicians completed the CSSI and patients completed the PSSI after each procedure. Patients completed the SF-12 Health Survey, Patient Satisfaction Questionnaire, and Socially Desirable Response Scale; clinicians completed the Observer's Assessment of Alertness Scale after procedures. Study patients were mostly women (59%), white (88%), had a mean age of 57.5 +/- 15.7 years, and had a colonoscopy (70%). Internal consistency reliabilities assessed result consistencies across test items. Coefficients greater than 0.70 indicate good reliability; greater than 0.85 indicate excellent reliability. Internal consistency reliabilities of the PSSI and CSSI total and subscale scores were greater than 0.76. Correlations were assessed using Pearson product moment correlation. PSSI and CSSI scores were correlated (P < .05). PSSI totals scores were correlated significantly with the SF-12 Health Survey (P < .05), the Patient Satisfaction Questionnaire (P < .05), and CSSI total scores were correlated with the Observer's Assessment of Alertness Scale (P < .01) and a visual analogue scale (P < .01). PSSI scores were not correlated with the Socially Desirable Response Scale (P > .05). The PSSI and CSSI provide for feasible, reliable, and valid assessment of procedural sedation satisfaction for outpatient colonoscopy and esophagogastroduodenoscopies and can be used for future sedation studies.


Circular harmonic averaging of noisy single-molecule images.
A new method for averaging of noisy single-molecule images has been developed. Averaging is done over the circular harmonic components of the images instead of over the images themselves. Those images which show different molecules or molecules in different projections can be separated into classes by comparing the power of their circular harmonic components, which is rotationally invariant. Orientational alignment, based on the rotational correlation of each image with all others, and averaging is performed separately for each class. Applying a quality measure to the circular harmonic averages allows separation of significant and nonsignificant components. Computer simulations indicate that the method is quite stable against noise. One of the main advantages of "circular harmonic averaging" over existing methods is that no reference images are needed in the averaging procedure.


The Role of Gay Identity Confusion and Outness in Sex-Seeking on Mobile Dating Apps Among Men Who Have Sex With Men: A Conditional Process Analysis.
Mobile dating apps are now a popular platform for men who have sex with men (MSM) to connect with others. Based on the uses and gratifications (U&G) theory, this study explores the relationship between sex-seeking and the number of casual sex partners met through MSM-based mobile dating apps (Grindr, Jack'd, and SCRUFF). The conditional process analysis (N = 401) shows that this relationship was significant and was mediated by the intensity of app use. That is, sex-seeking indirectly affected the number of casual sex partners through the intensity of app use. Furthermore, gay identity confusion and outness to the world moderated this indirect effect: it was stronger when the user was either more confused about his sexuality or was less out to the world. This research introduces an alternative way to incorporate psychographics variables into the U&G framework.


Vacuum-soaking of wood chip shiitake (Lentinula edodes) logs to reduce soak time and log weight variability and to stimulate mushroom yield.
Synthetic logs were vacuum-soaked or regular-soaked to determine the effects of soaking on yield and mushroom size, log weight variability and water distribution within the log. Yields (g/log) from substrates vacuum-soaked were higher by 26.7%, 18.6% and 35.8% (mean = 27.2%) for crops I, II and III, respectively, when compared with regular-soaked. However, mushroom size averaged only 11.2 g for vacuum-soaked logs vs 17 g for regular-soaked logs (51.8% larger for regular-soaked). The time required for vacuum-soaking logs was generally less than 3 min, compared with regular-soaking times ranging over 3-15 h. Water tended to accumulate more in the outside zone in the vacuum-soaked logs, compared with regular-soaked logs. Mean moisture contents for crops I and II for outside, middle and interior zones of vacuum-soaked logs were 66%, 47.5% and 42.2%, respectively, while regular-soaked logs for the same zones were 62.4%, 52.1% and 50.9%, respectively. Vacuum-soaked log weights had lower standard deviations than weights for regular-soaked logs in four out of six soaks, indicating a more uniform soaking process.


Lipid peroxidation products mediate the formation of 8-hydroxydeoxyguanosine in DNA.
Membrane lipid peroxidation processes yield products that may react with DNA to cause oxidative modifications. We have investigated this possibility and have found that calf thymus DNA exposed to autooxidized lipids causes the formation of 8-hydroxy-2'-deoxyguanosine (8-OH-dG). 8-OH-dG formation in DNA was measured using high-pressure liquid chromatography with electrochemical detection. Methyl linolenate oxidized for different lengths of time was exposed to DNA. The amount of 8-OH-dG formed in DNA was proportional to the amount of lipid peroxidation as measured by the thiobarbituric reactive substances present. The formation of 8-OH-dG in DNA by autooxidized methyl linolenate was dependent on the presence of the transition metal ions Cu or Fe and was inhibited by various scavengers, including superoxide dismutase and catalase. This implicates the involvement of oxygen free radicals in the process. Liposomes formed from phosphatidylcholine (82%) and methyl arachidonate (18%) were peroxidized for different lengths of time and then exposed to DNA. 8-OH-dG was formed in DNA by exposure to Cu(II) and peroxidized liposomes. Under these conditions, Fe(III) was slightly less effective than Cu(II) in mediating 8-OH-dG formation. These observations clearly show that 8-OH-dG formation in DNA may result from processes that may occur during intracellular lipid peroxidation.


Synthesis and antifungal evaluation of 6-(N-arylamino)-7-methylthio-5,8-quinolinediones.
A series of 6-(N-arylamino)-7-methylthio-5,8-quinolinedione derivatives 4a-4l was newly synthesized for the evaluation of antifungal activity. 6-(N-Arylamino)-7-methylthio-5,8-quinolinediones were prepared by regioselective nucleophilic substitution of 6,7-dichloro-5,8-quinolinediones with arylamines in the presence of Ce3+, and Na2S/dimethylsulfate. The MIC values of 4a-4l were determined for antifungal susceptibility in vitro against Candida species by agar streak method. The derivatives 4a-4l had generally potent antifungal activities against all human pathogenic fungi. Especially they had the most potent activity against C. krusei at 12.5-0.8 micrograms/ml. Compounds 4d, 4g, 4h, 4j and 4k had more potent antifungal activities than fluconazole. Compounds 4g and 4h completely inhibited the fungal growth at 0.8-6.3 micrograms/ml against all Candida species, while fluconazole inhibited the growth at 25 micrograms/ml. The compounds such as 4g and 4h containing an N-(4-bromo-2-methylphenyl)- or N-(4-bromo-3-methylphenyl)amino substituent exhibited the most potent antifungal activities.