Ant genera identification using an ensemble of convolutional neural networks.
Works requiring taxonomic knowledge face several challenges, such as arduous identification of many taxa and an insufficient number of taxonomists to identify a great deal of collected organisms. Machine learning tools, particularly convolutional neural networks (CNNs), are then welcome to automatically generate high-performance classifiers from available data. Supported by the image datasets available at the largest online database on ant biology, the AntWeb (www.antweb.org), we propose here an ensemble of CNNs to identify ant genera directly from the head, profile and dorsal perspectives of ant images. Transfer learning is also considered to improve the individual performance of the CNN classifiers. The performance achieved by the classifiers is diverse enough to promote a reduction in the overall classification error when they are combined in an ensemble, achieving an accuracy rate of over 80% on top-1 classification and an accuracy of over 90% on top-3 classification.


Rapid, specific, simple, in-field detection of Xanthomonas campestris pathovar musacearum by loop-mediated isothermal amplification.
To develop and evaluate a loop-mediated isothermal amplification (LAMP) assay for Xanthomonas campestris pathovar musacearum (Xcm), the causal agent of banana Xanthomonas wilt, a major disease of banana in Africa. LAMP primers were designed to the general secretion pathway protein D gene and tested against 17 isolates of Xcm encompassing the known genetic and geographic diversity of the bacterium and all isolates were detected. Seventeen other Xanthomonas isolates, including closely related Xanthomonas vasicola, other bacterial pathogens/endophytes of Musa and two healthy Musa varieties gave negative results with the LAMP assay. The assay showed good sensitivity, detecting as little as 51 fg of Xcm DNA, a greater level of sensitivity than that of an Xcm PCR assay. Amplification with the LAMP assay was very rapid, typically within 9 min from bacterial cultures. Symptomatic field samples of Musa from Uganda were tested and all produced amplification in less than 13 min. The LAMP assay provides rapid, sensitive detection of the pathogen that is ideally suited for deployment in laboratories with basic facilities and in-field situations. This is the first LAMP assay for Xcm which provides a significant improvement compared to existing diagnostics.


CCR4 promotes medullary entry and thymocyte-dendritic cell interactions required for central tolerance.
Autoimmunity results from a breakdown in central or peripheral tolerance. To establish central tolerance, developing T cells must enter the thymic medulla, where they scan antigen-presenting cells (APCs) displaying a diverse array of autoantigens. If a thymocyte is activated by a self-antigen, the cell undergoes either deletion or diversion into the regulatory T cell (T reg) lineage, thus maintaining self-tolerance. Mechanisms promoting thymocyte medullary entry and interactions with APCs are incompletely understood. CCR4 is poised to contribute to central tolerance due to its expression by post-positive selection thymocytes, and expression of its ligands by medullary thymic dendritic cells (DCs). Here, we use two-photon time-lapse microscopy to demonstrate that CCR4 promotes medullary entry of the earliest post-positive selection thymocytes, as well as efficient interactions between medullary thymocytes and DCs. In keeping with the contribution of thymic DCs to central tolerance, CCR4 is involved in regulating negative selection of polyclonal and T cell receptor (TCR) transgenic thymocytes. In the absence of CCR4, autoreactive T cells accumulate in secondary lymphoid organs and autoimmunity ensues. These studies reveal a previously unappreciated role for CCR4 in the establishment of central tolerance.


Musashi-1 regulates AKT-derived IL-6 autocrinal/paracrinal malignancy and chemoresistance in glioblastoma.
Glioblastoma multiform (GBM) is one of the most lethal human malignant brain tumors with high risks of recurrence and poor treatment outcomes. The RNA-binding protein Musashi-1 (MSI1) is a marker of neural stem/progenitor cells. Recent study showed that high expression level of MSI1 positively correlates with advanced grade of GBM, where MSI1 increases the growth of GBM. Herein, we explore the roles of MSI1 as well as the underlying mechanisms in the regulation of drug resistance and tumorigenesis of GBM cells. Our results demonstrated that overexpression of MSI1 effectively protected GBM cells from drug-induced apoptosis through down-regulating pro-apoptotic genes; whereas inhibition of AKT withdrew the MSI1-induced anti-apoptosis and cell survival. We further showed that MSI1 robustly promoted the secretion of the pro-inflammatory cytokine IL-6, which was governed by AKT activity. Autonomously, the secreted IL-6 enhanced AKT activity in an autocrine/paracrine manner, forming a positive feedback regulatory loop with the MSI1-AKT pathway. Our results conclusively demonstrated a novel drug resistance mechanism in GBM cells that MSI1 inhibits drug-induced apoptosis through AKT/IL6 regulatory circuit. MSI1 regulates both cellular signaling and tumor-microenvironmental cytokine secretion to create an intra- and intercellular niche for GBM to survive from chemo-drug attack.


Expression of uncharacterized male germ cell-specific genes and discovery of novel sperm-tail proteins in mice.
The identification and characterization of germ cell-specific genes are essential if we hope to comprehensively understand the mechanisms of spermatogenesis and fertilization. Here, we searched the mouse UniGene databases and identified 13 novel genes as being putatively testis-specific or -predominant. Our in silico and in vitro analyses revealed that the expressions of these genes are testis- and germ cell-specific, and that they are regulated in a stage-specific manner during spermatogenesis. We generated antibodies against the proteins encoded by seven of the genes to facilitate their characterization in male germ cells. Immunoblotting and immunofluorescence analyses revealed that one of these proteins was expressed only in testicular germ cells, three were expressed in both testicular germ cells and testicular sperm, and the remaining three were expressed in sperm of the testicular stages and in mature sperm from the epididymis. Further analysis of the latter three proteins showed that they were all associated with cytoskeletal structures in the sperm flagellum. Among them, MORN5, which is predicted to contain three MORN motifs, is conserved between mouse and human sperm. In conclusion, we herein identify 13 authentic genes with male germ cell-specific expression, and provide comprehensive information about these genes and their encoded products. Our finding will facilitate future investigations into the functional roles of these novel genes in spermatogenesis and sperm functions.


Two new naphthoquinone derivatives from Sinningia conspicua (Gesneriaceae).
Two new naphthoquinones, 7-hydroxy-2-O-methyldunniol (1) and 7-methoxy-2-O-methyldunniol (2) were isolated from the tubers of Sinningia conspicua (Seem.) G. Nicholson (Gesneriaceae). Nine known compounds were also obtained: 7-methoxydunniol (3), dunniol (4), 7-methoxy-α-dunnione (5), 7-hydroxydunnione (6), 2,4,4',6-tetramethoxychalcone (7), loureirin B (8), allo-calceolarioside A (9), β-sitosterol (10) and stigmasterol (11). This is the first report of compounds 3 and 5 in Sinningia. n-Hexane, ethyl acetate and ethanol extracts, and compounds 1-5 were tested for cytotoxic activity against PC-3 (prostate) and SKMEL 103 (melanoma) human tumour cell lines and also against the 3T3 (fibroblast) non-cancer cell line. All samples were inactive.


Building face composites can harm lineup identification performance.
Face composite programs permit eyewitnesses to build likenesses of target faces by selecting facial features and combining them into an intact face. Research has shown that these composites are generally poor likenesses of the target face. Two experiments tested the proposition that this composite-building process could harm the builder's memory for the face. In Experiment 1 (n = 150), the authors used 50 different faces and found that the building of a composite reduced the chances that the person could later identify the original face from a lineup when compared with no composite control conditions or with yoked composite-exposure control conditions. In Experiment 2 (n = 200), the authors found that this effect generalized to a simulated-crime video, but mistaken identifications from target-absent lineups were not inflated by composite building.


Interactions of acetylcholine and epinephrine on the dynamics of insulin release in vitro.
An in vitro system for perifusion of rat pancreatic islets has been utilized to define the effects of epinephrine on acetylcholine-induced insulin release over varying concentrations of the two agents. Perifusion of islets with epinephrine before challenge with acetycholine produced marked enhancement of both phases of cholinergically induced insulin release; enhancement of the first phase being more marked with increase in acetylcholine concentration and the converse being observed with the second phase. Perifusion of islets with epinephrine during stimulation with acetylcholine produced inhibition of insulin release, an effect dependent upon the concentration of epinephrine and of acetylcholine. There was an order of difference in the acetycholine concentration needed to overcome significant epinephrine-mediated inhibition of the first phase of insulin release (5 X 10(-4) mug/ml) and that needed to overcome inhibition of the second phase (5 X 10(-3) mug/ml). Comparison of the effects of various concentrations of epinephrine on glucose- and acetyl-choline-induced insulin release revealed that epinephrine was a less potent inhibitor of the first phase of acetylcholine-induced insulin release than of the first phase of glucose-induced insulin release. These data provide some insight into the potential interactions between cholinergic and adrenergic autonomic systems in modifying insulin release.


Biotechnological Potential of Bdellovibrio and Like Organisms and Their Secreted Enzymes.
Bdellovibrio and like organisms (BALOs) are obligate predatory bacteria that selectively prey on a broad range of Gram-negative bacteria, including multidrug-resistant human pathogens. Due to their unique lifestyle, they have been long recognized as a potential therapeutic and biocontrol agent. Research on BALOs has rapidly grown over the recent decade, resulting in many publications concerning molecular details of bacterial predation as well as applications thereof in medicine and biotechnology. This review summarizes the current knowledge on biotechnological potential of obligate predatory bacteria and their secreted enzymes.


HPLC analyses and pharmacokinetic studies of baicalin and oxymatrine in rabbits.
In the present study two simple RP-HPLC methods were developed to determine baicalin and oxymatrine in rabbit serum. Separation was performed on a Diamonsil C18 column (200 mm x 4.6 mm I.D., 5 microm) with UV detector at 277 nm for baicalin and 220 nm for oxymatrine. The mobile phase was methanol-water-phosphoric acid 50:50:0.2 v/v for baicalin and acetonitrile-water (20:80, v/v, 5 mmol/L sodium octanesulfonate was contained and pH was adjusted to 3.2 with phosphoric acid for oxymatrine. p-Nitrobenzoic acid and phenacetin were used as internal standards for baicalin and oxymatrine, respectively. The standard curves were linear from 0.5 to 200.0 mg/L for baicalin and from 0.5 to 100.0 mg/L for oxymatrine with correlation coefficients of 0.9994 and 0.9965, respectively. The intra-day and inter-day RSD were less than 5.4% and 7.2% for baicalin and 6.6% and 13.8% for oxymatrine. The mean recoveries were 100.1% for baicalin and 99.1% for oxymatrine. The methods were applied to a pharmacokinetic study of baicalin and oxymatrine in rabbits. The pharmacokinetic parameters were determined after intravenous injections of baicalin and oxymatrine (40 mg/kg) separately and together to rabbits. They all fit to the two-compartment open model. Student's t test shows that there is no significant difference in the main pharmacokinetic parameters including AUC(0-infinity), when alpha and beta, when baicalin and oxymatrine were administered separately or together.


Lessons learned during the war in Ukraine: a report from the Renal Disaster Relief Task Force of the ERA.
People living with kidney disease are among the most vulnerable at times of natural or man-made disasters. In addition to their unpredictable course, armed conflicts impose a major threat given the disruption of infrastructure, sanitation and access to food, water and medical care. The ongoing war in Ukraine has once more demonstrated the importance of preparedness, organization, coordination and solidarity during disasters. People living with kidney disease face serious challenges given their dependence on life-sustaining treatment, irrespective of whether they remain in the war zone or are displaced internally or externally. This especially affects those requiring kidney replacement therapy, dialysis or transplantation, but also patients with other kidney diseases and the medical staff who care for them. Soon after the war started, the European Renal Association assigned a Renal Disaster Relief Task Force dedicated to support the people living with kidney disease and the nephrology community in Ukraine. This report summarizes the major challenges faced, actions taken and lessons learned by this task force. We anticipate that the experience will help to increase preparedness and mitigate the devastating effects of armed conflicts on the kidney community in the future and propose to establish an international collaboration to extend this effort to other parts of the world facing similar challenges.


[The sacroiliac joint dysfunction: clinical manifestations, diagnostics and manual therapy].
Sacroiliac joint dysfunction is one of the proved causes of sacroiliac joint syndrome. We are talking about the restricted mobility of sacrum opposite to ilium the type of "reversible blockage of movement". Main characteristics of dysfunction are as follows: restricted "joint play", referred pain, normal radiological finding, normal lab results and disappearance of clinical symptoms after deblocking of articular bodies. Pain from a blocked joint can be referred to lower back, buttocks, hip, groin, thigh, calf and lower part of abdomen. Dispersion of painful regions is a consequence of a complex and variable innervation of articular capsule. Blocked position of articular bodies and protracted tension of articular capsule causes a stimulus of nociceptors by which a capsule is protected. Nociceptive activity is manifested with referred pains in innervational region of stimulated sensitive nerves. In the article, besides the clinical manifestations, there is described a diagnostics and manual therapy of dysfunction. Springing tests by means of which a passive mobility ("joint play") is being tested, are most valuable in dysfunction diagnostics. Manual therapy (mobilization/manipulation) is indicated and efficacious with the patients suffering from dysfunction.


The Complement C3a-C3aR Axis Promotes Development of Thoracic Aortic Dissection via Regulation of MMP2 Expression.
Thoracic aortic dissection (TAD), once ruptured, is devastating to patients, and no effective pharmaceutical therapy is available. Anaphylatoxins released by complement activation are involved in a variety of diseases. However, the role of the complement system in TAD is unknown. We found that plasma levels of C3a, C4a, and C5a were significantly increased in patients with TAD. Elevated circulating C3a levels were also detected in the developmental process of mouse TAD, which was induced by β-aminopropionitrile monofumarate (BAPN) treatment, with enhanced expression of C1q and properdin in mouse dissected aortas. These findings indicated activation of classical and alternative complement pathways. Further, expression of C3aR was obviously increased in smooth muscle cells of human and mouse dissected aortas, and knockout of C3aR notably inhibited BAPN-induced formation and rupture of TAD in mice. C3aR antagonist administered pre- and post-BAPN treatment attenuated the development of TAD. We found that C3aR knockout decreased matrix metalloproteinase 2 (MMP2) expression in BAPN-treated mice. Additionally, recombinant C3a stimulation enhanced MMP2 expression and activation in smooth muscle cells that were subjected to mechanical stretch. Finally, we generated MMP2-knockdown mice by in vivo MMP2 short hairpin RNA delivery using recombinant adeno-associated virus and found that MMP2 deficiency significantly reduced the formation of TAD. Therefore, our study suggests that the C3a-C3aR axis contributes to the development of TAD via regulation of MMP2 expression. Targeting the C3a-C3aR axis may represent a strategy for inhibiting the formation of TAD.


The ideal glass transition of hard spheres.
We use the replica method to study the ideal glass transition of a liquid of identical hard spheres. We obtain estimates of the configurational entropy in the liquid phase, of the Kauzmann packing fraction phi(K), in the range of 0.58-0.62, and of the random close packing density phi(c), in the range of 0.64-0.67, depending on the approximation we use for the equation of state of the liquid. We also compute the pair-correlation function in the glassy states (i.e., dense amorphous packings) and we find that the mean coordination number at phi(c) is equal to 6. All these results compare well with numerical simulations and with other existing theories.


A Parallel Spiking Neural Network Based on Adaptive Lateral Inhibition Mechanism for Objective Recognition.
Spiking neural network (SNN) has attracted extensive attention in the field of machine learning because of its biological interpretability and low power consumption. However, the accuracy of pattern recognition cannot completely surpass deep neural networks (DNNs). The main reason is that the inherent nondifferentiability of spiking neurons makes SNN unable to be trained directly by the gradient descent algorithm, and there is also no unified training algorithm for SNN. Inspired by the biological vision system, this paper proposes a parallel convolution SNN structure combined with an adaptive lateral inhibition mechanism. And, a way of dynamically evolving the time constant with the training of SNN is proposed to ensure the diversity of neurons. This paper verifies the effectiveness of the proposed methods on static datasets and neuromorphic datasets and extends it to the recognition of breast tumors. Experimental results show that the SNN has obvious advantages in dynamical datasets. For breast tumors, it is also an edge-based task, because the edge of a medical image contains the most important information in the image. This kind of information can provide great help for the noninvasive and accurate diagnosis of diseases. The Experimental results show that the proposed method is very close to the recognition results of DNNs on static datasets, and its performance on neuromorphic datasets exceeds that of DNNs.


Comparison of outcome measures from different pathways following total knee arthroplasty.
The benefits of extended inpatient rehabilitation following total knee arthroplasty (TKA) in local community hospitals (CHs) are unproven. Our study compared functional outcomes between patients discharged home and to CHs following TKA. A case-control study was conducted of patients undergoing primary unilateral TKA. Consecutive patients (n = 1,065) were retrospectively reviewed using the Knee Society Clinical Rating System (KSCRS), 36-item Short Form Health Survey (SF-36) and Oxford Knee Score (OKS) preoperatively, and at the six-month and two-year follow-ups. Overall, 967 (90.8%) patients were discharged home and 98 (9.2%) to CHs. CH patients were older (mean age 70.7 vs. 67.2 years; p < 0.0001), female (86.7% vs. 77.5%; p = 0.0388) and less educated (primary education and above: 61.7% vs. 73.8%; p = 0.0081). Median CH length of stay was 23.0 (range 17.0-32.0) days. Significant predictors of discharge destination were older age, female gender, lower education, and poorer ambulatory status and physical health. Preoperatively, CH patients had worse KSCRS Function (49.2 ± 19.5 vs. 54.4 ± 16.8; p = 0.0201), SF-36 Physical Functioning (34.3 ± 22.6 vs. 40.4 ± 22.2; p = 0.0017) and Social Functioning (48.2 ± 35.1 vs. 56.0 ± 35.6; p = 0.0447) scores. CH patients had less improvement for all scores at all follow-ups. Regardless of preoperative confounders, with repeated analysis of variance, discharge destination was significantly associated with KSCRS, SF-36 and OKS scores. Older, female and less educated patients with poorer preoperative functional scores were more likely to be discharged to CHs after TKA. At the two-year follow-up, patients in CHs had less improvement in functional outcomes than those discharged home.


Increased serum IL-17 and IL-23 in the patient with ankylosing spondylitis.
Interleukin 17 (IL-17) is a Th17 cytokine associated with inflammation, autoimmunity, and defense against some bacteria; it has been implicated in many chronic autoimmune diseases including psoriasis, multiple sclerosis, and systemic sclerosis. However, whether IL-17 plays a role in the pathogenesis of ankylosing spondylitis (AS) remains unclear. To analyze the content of IL-17 and IL-23 in the serum from patients with AS compared with health control subject, 50 patients with AS and 43 healthy volunteers were recruited. Serum IL-17 levels were examined by enzyme linked immunosorbent assay (ELISA). Statistic analyses were performed by SPSS 13.0. Results show that the serum IL-17 and IL-23 levels were significantly elevated in AS patients as compared with normal controls. Nevertheless, no associations of serum IL-17 and IL-23 levels with clinical and laboratory parameters were found; no significant difference regarding serum IL-17 and IL-23 levels was found between less active AS and more active AS. However, there was a strong positive association between the serum levels of IL-17 and IL-23 in the AS patients. Our results indicate increased serum IL-17 and IL-23 levels in AS patients, suggesting that this two cytokine may play critical roles in the pathogenesis of AS. Therefore, further studies are required to confirm this preliminary data.


The dynamics of single enzyme reactions: A reconsideration of Kramers' model for colored noise processes.
The utility of an approximate heuristic version of Kramers' theory of reaction rates that was earlier used [Chaudhury and Cherayil, J. Chem. Phys. 125, 024904 (2006)] to successfully describe the nonexponential waiting time distributions of the enzyme beta-galactosidase is reassessed. The original model, based on the Smoluchowski equation, is reformulated in terms of the phase space variables of the reaction coordinate, without neglecting inertial contributions. A new derivation of the Fokker-Planck equation (FPE) that describes the dynamics of this coordinate is presented. This derivation, based on functional methods, provides a more direct alternative to the existing distribution function approach used by Hanggi and Mojtabai [Phys. Rev. A 26, 1168 (1982)]. The time-dependent coefficients in the FPE, when incorporated into the exact expression for the transmission coefficient obtained from a reactive-flux formalism [Kohen and Tannor, J. Chem. Phys. 103, 6013 (1995)], are found to yield virtually the same results as the earlier heuristic model.


Alterations in constituent urinary proteins in response to bladder outlet obstruction in rats.
Benign prostatic hyperplasia, resulting in bladder outflow obstruction, induces well recognized clinical symptoms and morphologic bladder changes. Despite these phenomenon, relatively little is known with regard to the precise molecular events occurring in the bladder as a consequence of obstruction. In an effort to screen for alterations in bladder gene expression induced by obstruction, and/or alterations in uroepithelial integrity, this study compared pre- and post-obstructive constituent urinary proteins in an animal model. Outlet obstruction was created using a previously established model system. Experimental animals were surgically obstructed for either 2 or 7 days, at which time the urine was aspirated and the bladders removed and weighed. Urinary proteins were separated using 2-D PAGE. Following comparison of sham versus experimental animals, microsequencing was performed on proteins that were down regulated. Duplicate experiments confirmed the presence of outflow obstruction. Statistically significant increases (p <0.01) in bladder weights were seen at 2 and 7 days in the obstructed groups as compared with both sham and control groups. 2-D PAGE demonstrated a down regulation of three urinary proteins post-obstruction. Microsequencing identified these proteins as prostatic steroid-binding protein C3 precursor (pI=5.5, MW=15000), glandular kallikrein 9 (S3) precursor (pI=6.2, MW=19000), and glandular kallikrein 8 (P1) precursor (pI=6.2, MW=33000). Bladder outflow obstruction alters constituent urinary protein composition in an animal model system. The precise etiology of these alterations remains to be defined.


Psychometric properties of a Thai version of the Richards-Campbell sleep questionnaire.
In critically ill patients, a poor sleep quality can escalate mortality and the length of hospital stays. Albeit being the gold standard for sleep assessment, polysomnography (PSG) is expensive and complicated. The Richards-Campbell sleep questionnaire (RCSQ) is another tool with proof of good correlation with PSG. RCSQ was translated into many languages. However, the Thai version (T-RCSQ) has not been developed. Our study aimed to translate the original RCSQ into Thai, to test the content validity and reliability, and to introduce the questionnaire into clinical practice at the surgical intensive care unit (SICU). Prospective cross-sectional study METHODS: This study enrolled 92 patients from the SICU between August 2019 and January 2020. The content validity of T-RCSQ was determined by the index of item-objective congruence (IOC). The reliability was tested by test-retest reliability at 7 am and 9 am after intensive care unit (ICU) admission. The internal consistency was expressed by Cronbach's alpha. Patients' demography was reported as percentage, mean and standard deviation, and median and interquartile range. The content validity and test-retest reliability of the T-RCSQ were 0.8 and 0.97, respectively. The internal consistency was 0.964. Most patients were female with American Society of Anesthesiologist physical status III. The mean RCSQ scores at 7 am and 9 am were 5.82 ± 2.15 cm and 5.61 ± 2.18 cm, respectively. The T-RCSQ is reliable and could be used as an alternative to PSG for sleep assessment of ICU patients. Further research is required to validate the T-RCSQ against PSG and to assess its impact on improving sleep quality and patients' clinical outcomes. T-RCSQ is a useful tool for sleep assessment in ICU. According to cost-effectiveness, convenience, and good reliability, it could be applied to determine proper sleep to minimize patient morbidity and mortality.


[Late results of surgical treatment of acute and chronic instability of the ulnar collateral ligaments].
A total of 113 patients with acute and chronic instability of the ulnar collateral ligament metacarpal phalangeal (MP) joint of the thumb were treated surgically between 1980 and 1985; 82 patients were followed up after a mean period of 10 years. Of 59 patients with acute injuries, 52 were painfree with full stability of the MP joint; 23 patients with chronic instability and tendon grafting also showed restoration of stability. Nevertheless, the range of motion was reduced severely and opposition of the thumb was impaired. The results of follow-up reveal that acute reattachment of the injured ulnar collateral ligament is more effective.


Why we need epidemiologic studies of polycystic ovary syndrome in Africa.
The primary objective of the Ghana Polycystic Ovary Syndrome Epidemiology and Phenotype (Ghana-PEP) study will be to assess the relevance and phenotypic distribution of polycystic ovarian syndrome (PCOS) in a medically unbiased population of reproductive-aged women. In addition, the study will also attempt to identify sociodemographic, environmental, and psychological factors that may play a role in the development of PCOS phenotype. The study aims to recruit 990 randomly selected women aged 18-45 years living in Nsawam, the district capital of the Nsawam-Adoagyiri Municipality, in the Eastern region of Ghana. Participants will complete a questionnaire with the aid of trained personnel, undergo a physical examination, and undergo ultrasonography and biochemical evaluations relevant to PCOS. It is anticipated that the study will provide the population prevalence and phenotypes, and distribution of PCOS.


Low-temperature and elastic properties of the 1/1 Tsai-type quasicrystal approximant GdCd6investigated by ultrasonic measurements.
Low-temperature and elastic properties of the quasicrystal approximant GdCd6have been investigated by means of an ultrasonic measurement. Salient elastic anomalies were observed in the temperature and magnetic field dependence of the principal elastic constants, most probably being associated with the successive multiple magnetic phase transitions showing up at low temperatures. Based on the experimental data, a magnetic field vs temperature phase diagram was constructed. In a zero magnetic field, at least four phases appear to exist. However, the phase diagram both for the magnetic field applied forH//⟨100⟩andH//⟨110⟩is richer, and interestingly some phase boundaries correspond to the development of field-induced phases, leading to the intricate magnetic phase diagram possibly with multiple ordered phases. We discuss the elastic and electronic properties at low temperatures, and also the nature of the multiple magnetic phase transitions of GdCd6.


Differing coping mechanisms, stress level and anorectal physiology in patients with functional constipation.
To investigate coping mechanisms, constipation symptoms and anorectal physiology in 80 constipated subjects and 18 controls. Constipation was diagnosed by Rome II criteria. Coping ability and anxiety/depression were assessed by validated questionnaires. Transit time and balloon distension test were performed. 34.5% patients were classified as slow transit type of constipation. The total colonic transit time (56 h vs 10 h, P<0.0001) and rectal sensation including urge sensation (79 mL vs 63 mL, P = 0.019) and maximum tolerable volume (110 mL vs 95 mL, P = 0.03) differed in patients and controls. Constipated subjects had significantly higher anxiety and depression scores and lower SF-36 scores in all categories. They also demonstrated higher scores of 'monitoring' coping strategy (14+/-6 vs 9+/-3, P = 0.001), which correlated with the rectal distension sensation (P = 0.005), urge sensation (P=0.002), and maximum tolerable volume (P = 0.035). The less use of blunting strategy predicted slow transit constipation in both univariate (P = 0.01) and multivariate analysis (P = 0.03). Defective or ineffective use of coping strategies may be an important etiology in functional constipation and subsequently reflected in abnormal anorectal physiology.


Comparison of local resection of the head of the pancreas combined with longitudinal pancreaticojejunostomy (frey procedure) and duodenum-preserving resection of the pancreatic head (beger procedure).
The etiology of pain in chronic pancreatitis may be ductal hypertension, increased parenchymal pressure, or neural damage. It is difficult to assess the severity of pain in this patient population, a problem made more challenging by the frequency of narcotic dependency. Therapeutic interventions developed to relieve the pain of chronic pancreatitis include denervation of the pancreas, decompression of the main duct of the pancreas, resection of part or all of the diseased pancreas, and reduction of pancreatic secretion. Operative intervention for patients with chronic pain is indicated when severe pain, complications of pain, or potential malignancy are present. The operations that consistently provide long-lasting pain relief all have in common resection of all or a portion of the head of the pancreas. Adverse effects on exocrine and endocrine function, nutrition, and quality of life are related to the amount of pancreas resected. The ideal procedure should be easy to perform, have a low morbidity and mortality rate, provide long-lasting pain relief, and not augment endocrine and exocrine insufficiency. No single operation fulfills this ideal. The local resection of the head of the pancreas combined with longitudinal pancreaticojejunostomy (LR-LPJ) proposed by Frey and the duodenum-preserving resection of the head of the pancreas (DPHR) proposed by Beger are discussed. The conceptualization, development, and technique of LR-LPJ are discussed, and comparisons of patient outcomes are made with the outcomes of other procedures for chronic pancreatitis.


The role of cytokines in classical Hodgkin lymphoma.
The clinical and pathologic features of classical Hodgkin lymphoma (cHL) reflect an abnormal immune response that is thought to be due to the elaboration of a variety of cytokines by the malignant Reed-Sternberg (RS) cells or surrounding tissues. The majority of cHL cases are characterized by expression of tumor necrosis factor receptor (TNFR) family members and their ligands, as well as an unbalanced production of Th2 cytokines and chemokines. Activation of TNFR members results in constitutive activation of nuclear factor-kappa B (NF-kappa B), a transcription factor important for the in vitro and in vivo growth of RS cell lines. The expression of Th2 cytokines and chemokines leads to the reactive infiltrate of eosinophils, Th2 cells, and fibroblasts characteristic of cHL, and can also contribute to a local suppression of Th1 cell-mediated cellular immune response. Another particularly important growth and survival factor for RS cell lines is the Th2 cytokine interleukin 13, which is also commonly expressed by primary RS cells. In approximately 40% of cHL cases, the presence of Epstein-Barr virus influences the Th1/Th2 balance toward the production of Th1 cytokines and chemokines, but this shift is apparently insufficient for the stimulation of an effective antitumor cell-mediated immune response. This review summarizes the current literature on cytokine expression by and activity on RS cell lines and primary cHL tissues, examines cytokine signaling pathways in RS cells, and discusses the role that cytokines play in the specific clinical and pathologic features of cHL.


NOx emission calculations for bulk carriers by using engine power probabilities as weighting factors.
An important marine pollution issue identified by the International Maritime Organization (IMO) is NOx emissions; however, the stipulated method for determining the NOx certification value does not reflect the actual high emission factors of slow-speed two-stroke diesel engines over long-term slow steaming. In this study, an accurate method is presented for calculating the NOx emission factors and total amount of NOx emissions by using the actual power probabilities of the diesel engines in four types of bulk carriers. The proposed method is suitable for all types and purposes of diesel engines, is not restricted to any operating modes, and is highly accurate. Moreover, it is recommended that the IMO-stipulated certification value calculation method be modified accordingly to genuinely reduce the amount of NOx emissions. The successful achievement of this level of reduction will help improve the air quality, especially in coastal and port areas, and the health of local residents. As per the IMO, the NOx emission certification value of marine diesel engines having a rated power over 130 kW must be obtained using specified weighting factor (WF)-based calculation. However, this calculation fails to represent the current actual situation. Effective emission reductions of 6.91% (at sea) and 31.9% (in ports) were achieved using a mathematical model of power probability functions. Thus, we strongly recommend amending the certification value of NOx Technical Code 2008 (NTC 2008) by removing the WF constraints, such that the NOx emissions of diesel engines is lower than the Tier-limits at any load level to obtain genuine NOx emission reductions.


Development of eosinophil peroxidase activity and concomitant alteration of the antioxidant defenses in the liver of mice infected with Schistosoma mansoni.
The tropical parasite Schistosoma mansoni causes granulomatous inflammation following lodging of eggs in portal capillaries. In vitro studies indicated that the host reaction should involve reactive oxygen intermediates; however, it is not known what occurs in vivo at the site of the disease. Moreover, the ultimate pathophysiological effects of oxidative processes depend upon antioxidant factors, which are investigated in this study. We explored the changes in the major enzyme activities involved in liver redox metabolism during the course of infection and, for some of them, the mRNA expression. We also measured the reduced glutathione and lipid peroxide levels in the liver. We found that the deposition of parasite eggs triggers the release of endogenous eosinophil peroxidase; enzyme activity developed in the immediate vicinity of the eggs and it increased dramatically with time. However, Cu,Zn-superoxide dismutase, catalase and glutathione peroxidase activities decreased drastically. In contrast, glutathione transferase was unaffected. There was no proportional decrease in mRNA levels for the H2O2 scavenging enzymes. Reduced glutathione concentrations also dropped as a result of infection. Lastly, a two-fold increase in the levels of hepatic products generated by lipid peroxidation was observed. These results show that on the one hand oxidative processes occurred at the site of granulomatous inflammation and on the other hand the antioxidant capacity of the liver decreased, leading to the generation of lipid peroxides. The resulting imbalance between pro- and anti-oxidant processes may play a central role in the pathology associated with schistosomiasis.


Distribution of furamidine analogues in tumor cells: influence of the number of positive charges.
Fluorescence microscopy has been used to study the cellular distribution properties of a series of DNA binding cationic compounds related to the potent antiparasitic drug furamidine (DB75). The compounds tested bear a diphenylfuran or a phenylfuranbenzimidazole unfused aromatic core substituted with one or two amidine or imidazoline groups. The synthesis of five new compounds is reported. The B16 melanoma cell line was used to compare the capacities of mono-, bis-, and tetracations to enter the cell and nuclei. The high-resolution fluorescence pictures show that in the furamidine series, the compounds with two or four positive charges selectively accumulate in the cell nuclei whereas, in most cases, those bearing only one positive charge show reduced cell uptake capacities. One of the monocationic compounds, DB607, distributes in the cytoplasm, possibly in mitochondria, with no distinct nuclear accumulation. In sharp contrast, furamidine and benzimidazole analogues, including the drug DB293 that forms DNA minor groove dimers, efficiently accumulate in the cell nuclei and the intranuclear distribution of these DNA minor groove binders is significantly different from that seen with the DNA intercalating drug propidium iodide. The results suggest that the presence of two amidine terminal groups plays a role in facilitating nuclear accumulation into cells, probably as a result of nucleic acid binding. The determination of DNA melting temperature increases on addition of these compounds supports the importance of DNA binding in nuclear uptake.


Bioimpedancemetry for the assessment of periodontal tissue inflammation: a numerical feasibility study.
In dentistry possible inflammatory episodes of oral cavity can be very frequent (periodontitis, mucositis, peri-implantitis) and they can have serious consequences. Indeed, peri-implantitis is still the principal cause of implant failure. Impedance values of biological tissues are related to the physiological/pathological state of the tissue itself. In fact, an inflamed site exhibits an impedance value lower than that of the corresponding healthy tissue. Based on these observations, the aim of this work is to determine if impedancemetric measurements are able to provide information about the inflammatory state of tissues. A numerical 3D model has been realized to simulate the measurement conditions present in the event of inflammation around a dental implant. The aim is to understand if it is possible to determine the presence of an inflamed tissue and to locate its site, so that the treatment could be specifically focused in that specific area. A simplified geometry reproducing the implant has been realized in order to validate the numerical model by means of experimental measurements. The obtained results are satisfactorily accurate, so the model can be considered reliable. Therefore, multiple simulations have been run on the original model to carry out a parametric study in terms of different conductivity values, different volumes of inflamed tissues and different measurement frequencies. The advantages and limits of such a method have been shown to properly define the main constraints for the system design.


Timing of Hepatitis B Vaccine Birth Dose in Exposed Newborns, Southwest Ethiopia: A Cross-Sectional Study.
Hepatitis B virus disease is a global acute and chronic communicable disease. Mother-to-child transmission is the reason for high carrier rates. Unvaccinated newborns infected through mother-to-child transmission are at >95% risk of developing chronic hepatitis B virus disease. Vaccination is the most effective measure to reduce the global incidence of hepatitis B virus disease. Despite the World Health Organization's target to achieve 90% of the hepatitis B vaccine birth dose by 2030, little is known about the vaccination status of exposed newborns. The present study aimed to determine the timing of the hepatitis B vaccine birth dose in exposed newborns in Southwest Ethiopia. An institution-based cross-sectional study was employed on 422 systematically selected exposed newborns from April 2, 2022, to August 28, 2022. A pretested, interviewer-administered questionnaire was used for data collection. Data were entered into Epi data 3.1 and exported into SPSS version 23 software for analysis. Both bivariable and multivariable binary logistic regressions were performed. Variables with a p-value <.05 at a 95% confidence interval (CI) were considered statistically significant. The proportion of neonates who received their first dose of the hepatitis B vaccine on time was 57 (42.5%) (95% CI: 38.3-46.1%). A higher likelihood of vaccinating their exposed newborns on time was associated with formal education (adjusted odds ratio [AOR] = 3.01, 95% CI: 2.21-7.09), four or more ANC visits (AOR = 2.33, 95% CI: 2.05-6.21), and husband engagement (AOR = 4.31, 95% CI: 2.03-6.34). The proportion of timely initiation of the hepatitis B vaccine birth dose in Southwest Ethiopia was low. Thus, strengthening health education on the hepatitis B vaccine, encouraging women to have at least four ANC visits, and encouraging male involvement help improve the timely administration of the hepatitis B vaccine.


Revision of the self-monitoring scale.
Snyder's (1974) Self-Monitoring Scale exhibits a stable factor structure that does not correspond to the five-component theoretical structure he presents. Sets of face-valid items that better approximate the theoretical structure are described. Correlations between these sets of items and measures of other constructs reveal that four of the five components are positively related to social anxiety. Effective social interaction is supposedly the high self-monitor's forte, and social anxiety appears to be incompatible with this. The correlational results therefore question the entire theory and indicate the need for a narrower definition of the construct. Adopting such a definition from Snyder's review article (1979), we present a 13-item Revised Self-Monitoring scale which measures only sensitivity to the expressive behavior of others and ability to modify self-presentation. A 20-item Concern for Appropriateness scale is also described. This scale measures 2 variables that are directly associated with social anxiety--cross-situational variability and attention to social comparison information. Both scales have acceptable internal consistency, and both yield 2 subscale scores as well as a total score. Prospective users of either scale are advised to treat the 3 scores separately.


The Unstable Restorer-of-fertility locus in pepper (Capsicum annuum. L) is delimited to a genomic region containing PPR genes.
Unstable Restorer-of-fertility (Rfu), conferring unstable fertility restoration in the pepper CGMS system, was delimited to a genomic region near Rf and is syntenic to the PPR-like gene-rich region in tomato. The use of cytoplasmic-genic male sterility (CGMS) systems greatly increases the efficiency of hybrid seed production. Although marker development and candidate gene isolation have been performed for the Restorer-of-fertility (Rf) gene in pepper (Capsicum annuum L.), the broad use of CGMS systems has been hampered by the instability of fertility restoration among pepper accessions, especially sweet peppers, due to the widespread presence of the Unstable Restorer-of-fertility (Rfu) locus. Therefore, to investigate the genetic factors controlling unstable fertility restoration in sweet peppers, we developed a segregation population (BC4F5) from crosses using a male-sterile line and an Rfu-containing line. Segregation did not significantly deviate from a 3:1 ratio for unstable fertility restoration to sterility, indicating single dominant locus control for unstable fertility restoration in this population. Genetic mapping delimited the Rfu locus to a 398 kb genomic region on chromosome 6, which is close to but different from the previously identified Rf-containing region. The Rfu-containing region harbors a pentatricopeptide repeat (PPR) gene, along with 10 other candidate genes. In addition, this region is syntenic to the genomic region containing the largest number of Rf-like PPR genes in tomato. Therefore, the dynamic evolution of PPR genes might be responsible for both the restoration and instability of fertility in pepper. During genetic mapping, we developed various molecular markers, including one that co-segregated with Rfu. These markers showed higher accuracy for genotyping than previously developed markers, pointing to their possible use in marker-assisted breeding of sweet peppers.


Polarization surface-charge density of single semiconductor quantum rods.
Electrostatic force microscopy was used to determine that single CdSe quantum rods (QRs) have a permanent polarization surface-charge density, an unexpected observation for supposedly well-shaped particles. The surface charge results from a slight angle between the QR sides and the direction of internal electric polarization. By contrast, despite the large dipole moment expected for CdSe QRs, none was observed. The unavoidable presence of permanently charged surfaces on CdSe QRs has the potential to impede the development of novel devices incorporating these materials.


[Alternative medicine methods applied in patients before surgical treatment of lumbar discopathy].
Case records of 200 patients operated on in 1998/99 for herniated lumbar disc in Neurosurgery Dept. showed that 95 patients (47.5%) had been treated previously by 148 alternative medical or non-medical procedures. The authors discuss the problem of non-conventional treatment methods applied for herniated lumbar disc by professionals or non professionals. The procedures are often dangerous.


Efficacy and Safety of Regorafenib With 2/1 Schedule for Patients ≥ 75 Years With Metastatic Colorectal Cancer (mCRC) After Failure of 2 Lines of Chemotherapy.
In the CORRECT (patients with metastatic COloRectal Cancer treated with REgorafenib or plaCebo after failure of standard Therapy) trial, regorafenib was proven to extend survival of patients with metastatic colorectal cancer (mCRC) that progressed after all available therapies. Grade 3 to 4 toxicity occurred in 54% of patients, and data on the activity and tolerability of regorafenib in elderly patients were scarce. The aim of this study was to evaluate the efficacy and safety of an alternative schedule, 2-week-on treatment and 1 week-off (2/1 schedule), of regorafenib for elderly patients with mCRC. Patients ≥ 75 years with mCRC who progressed after oxaliplatin- and irinotecan-based chemotherapy received regorafenib on a 2/1 schedule. Potentially frail subjects were identified by G8 screening tool and excluded. The 2-month disease-control rate was the primary endpoint, and the secondary endpoints included safety, progression-free survival (PFS), overall survival (OS), and objective response rate. Between February 2014 and May 2017, 23 patients with mCRC were recruited at our institution. No partial or complete responses were observed, and the stable disease and disease-control rate were 52.2%. The median PFS was 4.8 months (95% confidence interval, 3.8-6.3 months), and the median OS was 8.9 months (95% confidence interval, 6.9-10.6 months). Adverse events were uncommon, and the most frequent grade 3 toxicity adverse events were hand-foot skin reaction (9%) and fatigue (9%). Toxicity-related dose reductions and discontinuations occurred in 5 and 2 patients, respectively. Regorafenib administered with a modified 2/1 schedule to patients who were aged ≥ 75 years and non-frail with treatment-refractory mCRC seems to be tolerable and achieve encouraging results in terms of PFS and OS.


Involvement of eotaxin, eosinophils, and pancreatic predisposition in development of type 1 diabetes mellitus in the BioBreeding rat.
Allergy and autoimmunity are both examples of deregulated immunity characterized by inflammation and injury of targeted tissues that have until recently been considered disparate disease processes. However, recent findings have implicated mast cells, in coordination with granulocytes and other immune effector cells, in the pathology of these two disorders. The BioBreeding (BB) DRlyp/lyp rat develops an autoimmune insulin-dependent diabetes similar to human type 1 diabetes mellitus (T1DM), whereas the BBDR+/+ rat does not. To better understand immune processes during development of T1DM, gene expression profiling at day (d) 40 (before insulitis) and d65 (before disease onset) was conducted on pancreatic lymph nodes of DRlyp/lyp, DR+/+, and Wistar-Furth (WF) rats. The eosinophil-recruiting chemokine, eotaxin, and the high-affinity IgE receptor (FcepsilonRI) were up-regulated >5-fold in d65 DRlyp/lyp vs d65 DR+/+ pancreatic lymph nodes by microarray (p < 0.05) and quantitative RT-PCR studies (p < 0.05). DR+/+, WF, and d40 DRlyp/lyp animals possessed normal pancreatic histology; however, d65 DRlyp/lyp animals possessed eosinophilic insulitis. Therefore, immunohistochemistry for pancreatic eotaxin expression was conducted, revealing positive staining of d65 DRlyp/lyp islets. Islets of d65 DR+/+ rats also stained positively, consistent with underlying diabetic predisposition in the BB lineage, whereas WF islets did not. Other differentially expressed transcripts included those associated with eosinophils, mast cells, and lymphocytes. These data support an important role for these inflammatory mediators in BB rat T1DM and suggest that the lymphopenia due to the Ian5/(lyp) mutation may result in a deregulation of cells involved in insulitis and beta cell destruction.


Association of the methylenetetrahydrofolate reductase A1298C but not the C677T single nucleotide polymorphism with sickle cell disease in Bahrain.
The association of methylenetetrahydrofolate reductase (MTHFR) gene mutations, C677T and A1298C, together with changes in homocysteine (Hcy) levels was investigated in 106 sickle cell disease patients and 156 healthy controls from Bahrain. The mutation analysis was done by restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR). While the frequencies of the mutant alleles C677T and A1298C were comparable between patients and controls, the frequency of the A1298C (C/C) (p = 0.03) but not C677T (T/T) (p = 0.67) genotype, and of the 677T/1298C haplotype were significantly higher in the patients (p = 0.05). Homocysteine levels were normal in all subjects. This suggests that the A1298C, but not C677T, mutation is associated with the genotype of sickle cell disease.


ETHE1 overexpression promotes SIRT1 and PGC1α mediated aerobic glycolysis, oxidative phosphorylation, mitochondrial biogenesis and colorectal cancer.
Ethylmalonic Encephalopathy Protein 1 (ETHE1) is a sulfur dioxygenase that regulates cellular H2S levels. We previously demonstrated a significant increase of ETHE1 expression in "single-hit" colon epithelial cells from crypts of patients with Familial Adenomatous Polyposis (FAP). Here, we report elevated levels of ETHE1 expression and increased mitochondrial density occurring in-situ in phenotypically normal FAP colorectal mucosa. We also found that constitutive expression of ETHE1 increased aerobic glycolysis ("Warburg effect"), oxidative phosphorylation, and mitochondrial biogenesis in colorectal cancer (CRC) cell lines, thereby depleting H2S which relieved the inhibition of phosphodiesterase (PDE), and increased adenosine monophosphate (AMP) levels. This led to activation of the energy sensing AMP-activated protein kinase (AMPKp), Sirtuin1 (SIRT1) and peroxisome proliferator-activated receptor γ coactivator 1α (PGC1α), a master regulator of mitochondrial biogenesis. By contrast, shRNA silencing of ETHE1 reduced PDE activity, AMPKp/SIRT1/PGC1α levels and mitochondrial biogenesis. Constitutive expression of ETHE1 accelerated both CRC cell xenograft and orthotopic patient derived xenograft CRC cell growth in vivo. Overall, our data nominate elevated ETHE1 expression levels as a novel biomarker and potential therapeutic target for the prevention of CRC tumorigenesis.


Assessment of personal qualities in selection of medical radiation science students.
It is increasingly acknowledged that, in addition to prior academic achievement, there is a need to seek evidence for the abilities and personal qualities of applicants to health professional programs at a university. The aim of this study was to determine the specific abilities and personal qualities required for excellence in practice in the relevant professional domains of medical radiation science (MRS). A focus group, consisting of MRS academic staff, developed a questionnaire. The questionnaire was sent to senior MRS practitioners throughout Australia and 213 were returned for analysis. Respondents were asked to rate 40 specific abilities and qualities (referred to as "elements") on a 5-point scale. Two hundred thirteen completed questionnaires were returned, a 53% response rate. One hundred twelve respondents (52%) indicated they currently worked in diagnostic radiography (DR), 57 (27%) worked in radiation therapy (RT), and 44 (21%) worked in nuclear medicine (NM). The duration (mean +/- SD) of the respondents' professional practice in MRS was 14.5 +/- 10 y, with durations ranging from 1 to 43 y. Raw scores and mean scores were examined for any influence of the variable "Number of Years in Practice." No major differences were found between the ratings provided by the practitioners from the 3 different MRS professional domains of NM, RT, and DR. Factor analysis indicated the existence of 3 orthogonal factors in the questionnaire data: (a) treat others professionally and ethically, (b) engage with and be open to others, and (c) problem-solving ability. Qualitative analysis of the respondents' comments provided similar themes: (a) the need for professional competence (knowledge and abilities), (b) ethical behavior, (c) the need for a technology and a people orientation, and (d) MRS should be the first choice of MRS students and not a second choice to other professional degrees. Senior medical radiation scientists identified professionalism, ethical behavior, engagement with and openness to others, intrinsic specific motivation, and an orientation to people and technology as nonacademic qualities required for excellence in the practice of the professions embraced by MRS.


Human acute stem cell leukemia with multilineage differentiation potential via cascade activation of growth factor receptors.
The morphologic, immunophenotypic, genotypic, genomic, and functional features of an undifferentiated acute leukemia with stem cell features are reported. At light and electron microscopy, the leukemic population was represented by primitive progenitor cells with no evidence of differentiation. The blasts were CD34(+), AC133(+), CD71(-), HLA-DR(-), CD38(-/dim+), CD90(+), CD117(dim+), flt3(+); did not express B, T, or myeloid-associated antigens; and showed a germline configuration of the immunoglobulin and T-cell receptor. Genomic profiling documented the expression of early stem cell and myeloid-associated genes. Receptors for early-acting hemopoietic growth factors (HGFs) were detected, while receptors for unilineage HGF were not expressed. Incubation with the flt3 or Kit ligand induced the expression of unilineage HGF receptors, allowing these cells to respond to their respective ligands. Growth without differentiation was sustained only in the presence of early-acting HGF, namely flt3 ligand, while early and unilineage HGF gave rise to all types of hemopoietic colonies.


[Optimization of extraction process of Dandelions (Taraxacum Weber)].
To optimize the extraction conditions of Dandelions (Taraxacum Weber). Using the uniform design, the content of total flavonoids and quercetin were detected to investigate the extraction process of Dandelions. The ethanol concentration and the ethanol volume in the uniform test impacted the test mostly. The best extraction process of Dandelions was obtained as following: 13 times of 85% ethanol as the solvent, extraction for 2 times and 1 h for each time. The extraction ratio of total flavonoids and quercetin are higher according to the above extraction process.


Characterization of mesenchymal stem cells in sheep naturally infected with scrapie.
Mesenchymal stem cells (MSCs) can be infected with prions and have been proposed as in vitro cell-based models for prion replication. In addition, autologous MSCs are of interest for cell therapy in neurodegenerative diseases. To the best of our knowledge, the effect of prion diseases on the characteristics of these cells has never been investigated. Here, we analysed the properties of MSCs obtained from bone marrow (BM-MSCs) and peripheral blood (PB-MSCs) of sheep naturally infected with scrapie — a large mammal model for the study of prion diseases. After three passages of expansion, MSCs derived from scrapie animals displayed similar adipogenic, chondrogenic and osteogenic differentiation ability as cells from healthy controls, although a subtle decrease in the proliferation potential was observed. Exceptionally, mesenchymal markers such as CD29 were significantly upregulated at the transcript level compared with controls. Scrapie MSCs were able to transdifferentiate into neuron-like cells, but displayed lower levels of neurogenic markers at basal conditions, which could limit this potential .The expression levels of cellular prion protein (PrPC) were highly variable between cultures, and no significant differences were observed between control and scrapie-derived MSCs. However, during neurogenic differentiation the expression of PrPC was upregulated in MSCs. This characteristic could be useful for developing in vitro models for prion replication. Despite the infectivity reported for MSCs obtained from scrapie-infected mice and Creutzfeldt–Jakob disease patients, protein misfolding cyclic amplification did not detect PrPSc in BM- or PB-MSCs from scrapie-infected sheep, which limits their use for in vivo diagnosis for scrapie.


Transcriptome changes associated with Tomato spotted wilt virus infection in various life stages of its thrips vector, Frankliniella fusca (Hinds).
Persistent propagative viruses maintain intricate interactions with their arthropod vectors. In this study, we investigated the transcriptome-level responses associated with a persistent propagative phytovirus infection in various life stages of its vector using an Illumina HiSeq sequencing platform. The pathosystem components included a Tospovirus, Tomato spotted wilt virus (TSWV), its insect vector, Frankliniella fusca (Hinds), and a plant host, Arachis hypogaea (L.). We assembled (de novo) reads from three developmental stage groups of virus-exposed and non-virus-exposed F. fusca into one transcriptome consisting of 72 366 contigs and identified 1161 differentially expressed (DE) contigs. The number of DE contigs was greatest in adults (female) (562) when compared with larvae (first and second instars) (395) and pupae (pre- and pupae) (204). Upregulated contigs in virus-exposed thrips had blastx annotations associated with intracellular transport and virus replication. Upregulated contigs were also assigned blastx annotations associated with immune responses, including apoptosis and phagocytosis. In virus-exposed larvae, Blast2GO analysis identified functional groups, such as multicellular development with downregulated contigs, while reproduction, embryo development and growth were identified with upregulated contigs in virus-exposed adults. This study provides insights into differences in transcriptome-level responses modulated by TSWV in various life stages of an important vector, F. fusca.


Predicting Maternal-Fetal Disposition of Fentanyl Following Intravenous and Epidural Administration Using Physiologically Based Pharmacokinetic Modeling.
Fentanyl is an opioid analgesic used to treat obstetrical pain in parturient women through epidural or intravenous route, and unfortunately can also be abused by pregnant women. Fentanyl is known to cross the placental barrier, but how the route of administration and time after dosing affects maternal-fetal disposition kinetics at different stages of pregnancy is not well characterized. To address this knowledge gap, we developed a maternal-fetal physiologically based pharmacokinetic (mf-PBPK) model for fentanyl to evaluate the feasibility to predict the maternal and fetal plasma concentration-time profiles of fentanyl after various dosing regimens. As fentanyl is typically given via the epidural route to control labor pain, an epidural dosing site was developed using alfentanil as a reference drug and extrapolated to fentanyl. Fetal hepatic clearance of fentanyl was predicted from CYP3A7-mediated norfentanyl formation in fetal liver microsomes (intrinsic clearance = 0.20 ± 0.05 µl/min/mg protein). The developed mf-PBPK model successfully captured fentanyl maternal and umbilical cord concentrations after epidural dosing and was used to simulate the concentrations after intravenous dosing (in a drug abuse situation). The distribution kinetics of fentanyl were found to have a considerable impact on the time course of maternal:umbilical cord concentration ratio and on interpretation of observed data. The data show that mf-PBPK modeling can be used successfully to predict maternal disposition, transplacental distribution, and fetal exposure to fentanyl. SIGNIFICANCE STATEMENT: This study establishes the modeling framework for predicting the time course of maternal and fetal exposures of fentanyl opioids from mf-PBPK modeling. The model was validated based on fentanyl exposure data collected during labor and delivery after intravenous or epidural dosing. The results show that mf-PBPK modeling is a useful predictive tool for assessing fetal exposures to fentanyl opioid therapeutic regimens and potentially can be extended to other drugs of abuse.


Identification of a Shared Cytochrome p4502E1 Epitope Found in Anesthetic Drug-Induced and Viral Hepatitis.
Cytochrome p4502E1 (CYP2E1) autoantibodies are biomarkers for drug-induced hepatitis and chronic hepatitis C. However, major histocompatibility-restricted CYP2E1 epitopes associated with these diseases have not been identified. We hypothesized that CYP2E1 epitopes associated with different types of hepatitis may be shared and may impact immune responses and metabolism. SYFPEITHI epitope prediction identified CYP2E1 candidate epitopes that would be recognized by MHC II haplotypes. Candidate epitopes were tested for induction of hepatitis and CYP2E1 autoantibodies in mice and recognition by sera from patients with anesthetic drug-induced and viral hepatitis. Human liver cells treated with epitope hybridoma serum were analyzed for mitochondrial stress. CYP2E1 activity was measured in human microsomes similarly treated. Epitope antibodies in viral hepatitis sera were analyzed using linear regression to uncover associations with liver pathology. A P value of <0.05 was considered significant. One epitope (Gly113-Leu135) induced hepatitis and CYP2E1 autoantibodies in mice after modification of Lys123 (P < 0.05). Gly113-Leu135 antiserum recognized mitochondria and endoplasmic reticula (P < 0.05), upregulated HSP27 (P < 0.01) and mitochondrial oxidative stress via complex 1 inhibition (P < 0.001), and inhibited CYP2E1 activity. Gly113-Leu135 IgG4 detected in viral hepatitis sera was associated with severe hepatic fibrosis (P = 0.0142). We found a novel CYP2E1 epitope that was detected in anesthetic and viral hepatitis and that triggered hepatitis in mice. Our findings may improve understanding of hepatic immune responses triggered by metabolism or viruses.IMPORTANCE Drug-induced hepatitis is the leading reason that an approved drug is removed from the commercial market. Halogenated anesthetics can induce hepatitis in susceptible persons, and cytochrome p4502E1 (CYP2E1) enzymes responsible for their metabolism induce antibodies in addition to hepatitis. CYP2E1 antibodies detected in anesthetic hepatitis patients have been detected in patients with viral hepatitis, suggesting that these different forms of hepatitis could develop immune reactions to a common segment or epitope of CYP2E1. We have found a common MHC-restricted CYP2E1 epitope in anesthetic and viral hepatitis that is a dominant epitope in anesthetic hepatitis and is significantly associated with fibrosis in patients with viral hepatitis. Along with conformational epitopes, our identification of MHC-restricted CYP2E1 epitopes can be used to develop specific diagnostic tests for drug-induced or viral hepatitis or associated fibrosis or to predict individuals at risk for developing these diseases or their sequelae.


The role of advanced practice clinicians in the availability of abortion services in the United States.
Although abortion is one of the most common surgical procedures performed in the United States, the number of abortion providers is declining. Advanced practice clinicians, including nurse practitioners and certified nurse-midwives, may help to alleviate this shortage. However, some states bar nonphysicians from performing abortions. Not only should training in abortion techniques be made available to nonphysician providers who desire it, but legal obstacles must also be overcome in order to allow advanced practice clinicians the right to provide abortion services.


Global and local priming in a multi-modal context.
Perceptual information can be processed at many different scales, from featural details to entire scenes. Attentional selection of different scales has been studied using hierarchical stimuli, with research elucidating a variety of biases in local and global attentional selection (due to, e.g., stimulus properties, brain injury, and experience). In this study, the emphasis is on biases produced through recent experience, or level-specific priming effects, which have been demonstrated within both the visual and auditory modalities. Namely, when individuals attend to local information, they are subsequently biased to attend locally (and similarly so with global attention). Here, these level-specific priming effects are investigated in a multi-modal context to determine whether cross-modal interactions occur between visual and auditory modalities during hierarchical processing. Specifically, the study addresses if attentional selection of local or global information in the visual modality subsequently biases auditory attentional selection to that level, and vice versa (i.e., level-priming). Though expected identity priming effects emerged in the study, no cross-modal level-priming effects manifested. Furthermore, the multi-modal context eliminated the well-established within-modality level-specific priming effects. Thus, though the study does reveal a multi-modal effect, it was not a level-based effect. Instead, paradoxically, the multi-modal context eliminated attentional scope biases (i.e., level-priming) within uni-modal transitions. In other words, when visual and auditory information are equally likely require attention, no persistence emerges for processing local or global information over time, even within a single modality.


Outcome at 2 years of children 23-27 weeks' gestation born in Victoria in 1991-92. The Victorian Infant Collaborative Study Group.
To determine the survival and sensorineural disability rates in very preterm infants born in 1991-92, and to compare the results with contemporaneous normal birthweight controls and with preterm infants born in 1985-87. This was a geographically determined cohort study in the state of Victoria, Australia of consecutive livebirths 23-27 weeks' gestational age born during 1991-92, and randomly selected contemporaneous normal birthweight (NBW) controls born during 1991-92 in the three level-III perinatal centres in the State. Consecutive livebirths 24-26 weeks gestational age born in the State during 1985-87 comprised another comparison group. The main outcome measures were survival and sensorineural disability rates at 2 years of age. Of the 401 livebirths 23-27 weeks in 1991-92, 225 (56.1%) survived to 2 years of age. The survival rate for those 24-26 weeks was 57.4% (143/249), a statistically significant increase on the regional survival rate of 30.1% (95/316) in 1985-87. In 1991-92 births, the survival rate rose significantly with increasing gestational age, and was significantly higher than in 1985-87 at each of 24, 25, and 26 weeks. Of sensorineural impairments in preterm survivors at 2 years of age, the rate of blindness was significantly lower in 1991-92 (2.3%) compared with 1985-87 (8.4%), and the overall rates of sensorineural disability were not statistically different in 1991-92 compared with 1985-87. In 1991-92 preterm survivors, the survival rate free of disability rose significantly with increasing gestational age, and as a percentage of survivors the rate of disability overall fell with increasing gestational age. However, the rate of disability overall was much higher in preterm infants than NBW controls. Survival rates of very preterm infants in this regional cohort have improved in the 1990s after the introduction of exogenous surfactant. Blindness at 2 years of age was significantly lower than in an earlier preterm cohort, but the rates of sensorineural disability still remain higher in very preterm survivors than for NBW controls. Although survival rates are lower and disability rates are higher with diminishing maturity, there is no obvious gestational age below which adverse neurological outcome in survivors would preclude active management on the basis of gestational age alone.


Mobility reversal of polyelectrolyte-grafted colloids in monovalent salt solutions.
We present molecular dynamics simulations on the electrophoresis of a negative colloid grafted with positive polyelectrolytes. Net-neutral colloids show a varying mobility in monovalent salt. For colloids with negative net charge the mobility is negative at low and positive at high salt concentrations. This mobility reversal is an electrokinetic effect, and thus different from that observed in multivalent salt. Our results agree with numerical calculations based on the Darcy-Brinkman formalism, with which we predict the mobility reversal to also occur for experimentally accessible colloids.


Epidemiology, causes, evolution and outcome in a single-center cohort of 1116 critically ill patients with hypoxic hepatitis.
Hypoxic hepatitis (HH) is a type of acute hepatic injury that is histologically characterized by centrilobular liver cell necrosis and that is caused by insufficient oxygen delivery to the hepatocytes. Typical for HH is the sudden and significant increase of aspartate aminotransferase (AST) in response to cardiac, circulatory or respiratory failure. The aim of this study is to investigate its epidemiology, causes, evolution and outcome. The screened population consisted of all adults admitted to the intensive care unit (ICU) at the Ghent University Hospital between January 1, 2007 and September 21, 2015. HH was defined as peak AST > 5 times the upper limit of normal (ULN) after exclusion of other causes of liver injury. Thirty-five variables were retrospectively collected and used in descriptive analysis, time series plots and Kaplan-Meier survival curves with multi-group log-rank tests. HH was observed in 4.0% of the ICU admissions at our center. The study cohort comprised 1116 patients. Causes of HH were cardiac failure (49.1%), septic shock (29.8%), hypovolemic shock (9.4%), acute respiratory failure (6.4%), acute on chronic respiratory failure (3.3%), pulmonary embolism (1.4%) and hyperthermia (0.5%). The 28-day mortality associated with HH was 45.0%. Mortality rates differed significantly (P = 0.007) among the causes, ranging from 33.3% in the hyperthermia subgroup to 52.9 and 56.2% in the septic shock and pulmonary embolism subgroups, respectively. The magnitude of AST increase was also significantly correlated (P < 0.001) with mortality: 33.2, 44.4 and 55.4% for peak AST 5-10× ULN, 10-20× ULN and > 20× ULN, respectively. This study surpasses by far the largest cohort of critically ill patients with HH. HH is more common than previously thought with an ICU incidence of 4.0%, and it is associated with a high all-cause mortality of 45.0% at 28 days. The main causes of HH are cardiac failure and septic shock, which include more than 3/4 of all episodes. Clinicians should search actively for any underlying hemodynamic or respiratory instability even in patients with moderately increased AST levels.


Autoimmune ocular disease in MRL/Mp-lpr/lpr mice is suppressed by anti-CD4 antibody.
MRL/Mp-lpr/lpr(MRL/lpr) mice spontaneously have a systemic autoimmune disease, characterized by vasculitis, lymphadenopathy, glomerulonephritis, and autoantibody formation. Among the many autoimmune lesions present are focal ocular inflammatory infiltrates, involving the choroid and sclera. These lesions appear to be related to the vasculitis seen in MRL/lpr mice and are mediated by L3T4-positive helper T-cells (CD4-positive T-cells). Systemic treatment of MRL/lpr mice with a monoclonal anti-L3T4 antibody (anti-CD4) resulted in a dramatic reduction of both the frequency and severity of the ocular disease, supporting the hypothesis that the CD4-positive T-cells play an essential role in the pathogenesis of the choroiditis and scleritis in this strain.


Black race and lower age at surgery are associated with smoking relapse in a safety-net setting after surgery for stage I non-small cell lung cancer.
Smoking relapse after surgical resection for lung cancer (LC) remains a health concern. This study aims to determine various factors associated with postoperative smoking relapse in patients undergoing surgical resection for stage I non-small cell lung cancer (NSCLC) at an urban safety net hospital. We analyzed the demographic and clinical variables of all patients who underwent surgical resection for stage I NSCLC from 2002 to 2016 at our institution. Based on the post-operative smoking history, we segregated the cohort into two groups: relapse and abstinent. Chi-squared and analysis of variance tests were used to identify the variables that registered a significant difference between the two groups. Further, we used univariable and multivariable logistic regression to determine association between variables and smoking relapse. We analyzed data from 168 patients, excluding those with inadequate smoking history and never smokers. In total, 64 (38.1%) patients experienced smoking relapse, and 104 (61.9%) remained abstinent. The age, annual income, and race showed significant differences between the two groups. Multivariable logistic regression reflected that black patients had higher odds of relapse than white patients [odds ratio (OR) =3.26, confidence interval (CI): 1.54-6.89, P=0.002] and the chances of relapse decreased as the age increased (5-year age gap, OR =0.70, CI: 0.58-0.85, P<0.001). Black race and younger age at the time of surgery are associated with smoking relapse after surgery for stage I NSCLC. Targeted smoking cessation programs catered towards these patient groups may help reduce the prevalence of post-operative smoking.


The impact of age at seizure onset on the likelihood of atypical language representation in children with intractable epilepsy.
Studies have suggested that early postnatal lesions are associated with a greater likelihood of atypical speech representation than lesions acquired later in life. Comparison groups have been defined differently across studies, with age typically being treated as a dichotomous (i.e., early versus late lesion onset) rather than continuous variable. Thus, little is known about the age at which children become less likely to exhibit atypical representation following a brain insult. This study examined the likelihood of typical versus atypical speech representation in children with intractable epilepsy (n = 75). Age of seizure onset was treated as a continuous variable to examine whether there was a naturally occurring cut-off point after which the rate of atypical speech representation decreased. A much higher proportion of children with seizure onset prior to the fifth year showed atypical speech representation as compared to children whose seizures began after 5 years of age.


Real space method for the electronic structure of one-dimensional periodic systems.
We present a real space pseudopotential method for calculating the electronic structure of one-dimensional periodic systems such as nanowires. As an application of this method, we examine H-passivated Si nanowires. The band structure and heat of formation of the Si nanowires are presented and compared to plane wave methods. Our method is able to offer the same accuracy as the traditional plane wave methods but offers a number of computational advantages such as faster convergence for heteropolar nanowires.


[Annual Report 2004 - French National Reference Centre for Rare Blood Groups and Immunohaematology (CNRGS)].
In 2004, the French Reference Centre for Rare Blood Groups and Immunohaematology (CNRGS) developed 7 types of activities: 1) Studies of complex Immunohaematology issues (IH), 2) Studies of rare blood phenotypes, 3) the transfusion of patients showing complex issues, 4) IH reactive control in consistency with the 98/79/CE European Directive, 5) European studies and expertise on reactives and techniques, 6) Biotechnologies applied to blood groups, in particular RH, KEL, FY, JK, DO and CO, 7) Implementation of allo-immunization research programs (cellular immunology and grafting issues). The CNRGS efficiency is based on the 'reference-research' link thanks to the Inserm partnership and direct applications to patients allowing to a better risk management and control.


Staged Arterial and Venous Embolizations in Treatment of Type IV Intraosseous Dural Arteriovenous Fistula.
This is a case report of an adult male with complex type IV intraosseous DAVF causing severe venous hypertension and bony destruction, presenting with severe hemotympanum, and a novel way of staged arterial and venous embolizations to treat the emergent symptoms. First and second stages were direct selective arterial embolizations using Onyx liquid agent. Goal was to reduce flow into the fistula by embolizing the feeder branch and distal penetration of the nidus with Onyx. The third stage was performed through the venous route: the transverse sinus and the sigmoid sinus were embolized using Penumbra Ruby coils and Onyx, two microcatheters were used and two large coils were placed simultaneously to form a stable coil mass, and the entire sinus was embolized using Coils and Onyx. Patient's venous hypertension and degree of hydrocephalus had significantly decreased after the procedure. He was able to return to work, but was instructed to avoid heavy lifting and placing anything in and around his right ear. Multiple step arterial and venous embolization procedures were successful in decreasing the frequency of hemotympanum, degree of hydrocephalus, and improving quality of life of this patient.


Changes in intestinal waste products during the antenatal management of gastroschisis by serial amniotic fluid exchange and infusion.
Despite the good survival rate of fetuses with gastroschisis, the length and cost of hospitalization for surgically repaired gastroschisis are high. In gastroschisis, prolonged exposure of the intestine to amniotic fluid (AF) containing intestinal waste products results in intestinal damage, including intestinal wall thickening and fibrous peel formation. The deleterious effects of AF on gastroschisis can be prevented by lowering the concentration of intestinal waste products. We describe the treatment of a case of fetal gastroschisis by repeated AF exchange and infusion. Following repeated, successful transabdominal AF exchange and infusion, the concentrations of various intestinal waste products were decreased. AF exchange and infusion may prevent intestinal damage and improve postnatal outcome in gastroschisis by diluting the AF, probably by lowering the concentrations of intestinal waste products.


Viaminate Inhibits Propionibacterium Acnes-induced Abnormal Proliferation and Keratinization of HaCat Cells by Regulating the S100A8/S100A9- MAPK Cascade.
Viaminate, a vitamin A acid drug developed in China, has been clinically used in acne treatment to regulate epithelial cell differentiation and proliferation, inhibit keratinization, reduce sebum secretion, and control immunological and anti-inflammatory actions; however, the exact method by which it works is unknown. In the present study, acne was induced in the ears of rats using Propionibacterium acnes combined with sebum application. After 30 days of treatment with viaminate, the symptoms of epidermal thickening and keratin overproduction in the ears of rats were significantly improved. Transcriptomic analysis of rat skin tissues suggested that viaminate significantly regulated the biological pathways of cellular keratinization. Gene differential analysis revealed that the S100A8 and S100A9 genes were significantly downregulated after viaminate treatment. The results of qPCR and Western blotting confirmed that viaminate inhibited the expression of S100A8 and S100A9 genes and proteins in rat and HaCat cell acne models, while its downstream pathway MAPK (MAPK p38/JNK/ERK1/2) protein expression levels were suppressed. Additional administration of the S100A8 and S100A9 complex protein significantly reversed the inhibitory effect of viaminate on abnormal proliferation and keratinization levels in acne cell models. In summary, viaminate can improve acne by modulating S100A8 and S100A9 to inhibit MAPK pathway activation and inhibit keratinocyte proliferation and keratinization levels.


Up-Regulation of RANK Expression via ERK1/2 by Insulin Contributes to the Enhancement of Osteoclast Differentiation.
Despite the importance of the receptor activator of nuclear factor (NF)-kappaB ligand (RANKL)-RANK signaling mechanisms on osteoclast differentiation, little has been studied on how RANK expression is regulated or what regulates its expression during osteoclastogenesis. We show here that insulin signaling increases RANK expression, thus enhancing osteoclast differentiation by RANKL. Insulin stimulation induced RANK gene expression in time- and dose-dependent manners and insulin receptor shRNA completely abolished RANK expression induced by insulin in bone marrow-derived monocyte/macrophage cells (BMMs). Moreover, the addition of insulin in the presence of RANKL promoted RANK expression. The ability of insulin to regulate RANK expression depends on extracellular signal-regulated kinase 1/2 (ERK1/2) since only PD98059, an ERK1/2 inhibitor, specifically inhibited its expression by insulin. However, the RANK expression by RANKL was blocked by all three mitogen-activated protein (MAP) kinases inhibitors. The activation of RANK increased differentiation of BMMs into tartrate-resistant acid phosphatase-positive (TRAP+) osteoclasts as well as the expression of dendritic cell-specific transmembrane protein (DC-STAMP) and d2 isoform of vacuolar (H+) ATPase (v-ATPase) Vo domain (Atp6v0d2), genes critical for osteoclastic cell-cell fusion. Collectively, these results suggest that insulin induces RANK expression via ERK1/2, which contributes to the enhancement of osteoclast differentiation.


[Evaluation of greenlight photoselective vaporization of prostate and plasmakinetic resection of prostate for the treatment of eldly benign prostatic hyperplasia men with high surgical risk: a prospective randomised control trial].
To compare the clinical effects and safety between greenlight photoselective vaporization of prostate (PVP) and plasmakinetic resection of prostate (PRP) in eldly benign prostatic hyperplasia (BPH) men with high surgical risk. METHODS; Fifty three eldly BPH patients, who had the indication of surgical treatment but complicated with at least one internal disease, were randomly divided into PVP group and PRP group. The clinical data of all the patients were collected and compared between the two groups, including pre-operative and post-operative international prostate symptom score (IPSS), postvoid residual urine (PVR), urine flow rate (Qmax), quality of life (QOL) as well as prostate volume (PV), operational time, operative bleeding volume, postoperative recovery, peri-operative complications. The complete follow-up data of 44 patients were achieved: 21 of PVP, 23 of PRP. There were significant differences between two groups in operative bleeding, bladder irrigation time, indwelling catheter time and hospital stay (P < 0.002). The peri-operative bleeding was lower in PVP group, while the bladder irrigation time, indwelling catheter time and hospital stay were shorter in PVP group. The operation time showed no difference (P = 0.12). No significant differences were found 3 months postoperatively between two groups in all the data associated with urination (IPSS, Qmax, PVR, QOL), P > 0.05. Complications (urethrostenosis, retrograde ejaculationwere acceptable in both groups. For surgical treatment of eldly men with high surgical risk, both PVP and PRP are safe and effective with the internal disease being sufficient control.


Mitochondrial cell death suppressors carried by human and murine cytomegalovirus confer resistance to proteasome inhibitor-induced apoptosis.
Human cytomegalovirus carries a mitochondria-localized inhibitor of apoptosis (vMIA) that is conserved in primate cytomegaloviruses. We find that inactivating mutations within UL37x1, which encodes vMIA, do not substantially affect replication in TownevarATCC (Towne-BAC), a virus that carries a functional copy of the betaherpesvirus-conserved viral inhibitor of caspase 8 activation, the UL36 gene product. In Towne-BAC infection, vMIA reduces susceptibility of infected cells to intrinsic death induced by proteasome inhibition. vMIA is sufficient to confer resistance to proteasome inhibition when expressed independent of viral infection. Murine cytomegalovirus m38.5, whose position in the viral genome is analogous to UL37x1, exhibits mitochondrial association and functions in much the same manner as vMIA in inhibiting intrinsic cell death. This work suggests a common role for vMIA in rodent and primate cytomegaloviruses, modulating the threshold of virus-infected cells to intrinsic cell death.


Virulence Characteristics of mecA-Positive Multidrug-Resistant Clinical Coagulase-Negative Staphylococci.
Coagulase-negative staphylococci (CoNS) are an important group of opportunistic pathogenic microorganisms that cause infections in hospital settings and are generally resistant to many antimicrobial agents. We report on phenotypic and genotypic virulence characteristics of a select group of clinical, mecA-positive (encoding penicillin-binding protein 2a) CoNS isolates. All CoNS were resistant to two or more antimicrobials with S. epidermidis strain 214EP, showing resistance to fifteen of the sixteen antimicrobial agents tested. Aminoglycoside-resistance genes were the ones most commonly detected. The presence of megaplasmids containing both horizontal gene transfer and antimicrobial resistance genetic determinants indicates that CoNS may disseminate antibiotic resistance to other bacteria. Staphylococcus sciuri species produced six virulence enzymes, including a DNase, gelatinase, lipase, phosphatase, and protease that are suspected to degrade tissues into nutrients for bacterial growth and contribute to the pathogenicity of CoNS. The PCR assay for the detection of biofilm-associated genes found the eno (encoding laminin-binding protein) gene in all isolates. Measurement of their biofilm-forming ability and Spearman's rank correlation coefficient analyses revealed that the results of crystal violet (CV) and extracellular polymeric substances (EPS) assays were significantly correlated (ρ = 0.9153, P = 3.612e-12). The presence of virulence factors, biofilm-formation capability, extracellular enzymes, multidrug resistance, and gene transfer markers in mecA-positive CoNS clinical strains used in this study makes them powerful opportunistic pathogens. The study also warrants a careful evaluation of nosocomial infections caused by CoNS and may be useful in studying the mechanism of virulence and factors associated with their pathogenicity in vivo and developing effective strategies for mitigation.


Comparison of five growth media and two anaerobic techniques for isolating bacteria from dental plaque.
Five agar media in combination with the Hungate roll tube technique and conventional anaerobic jar technique (Baird & Tatlock¿ jars) were evaluated to determine the most suitable medium for non-selective isolation of the viable microorganisms in dental plaque. The highest colony count was obtained by using "Modified Medium 10" with the roll tube technique. About twice as many plaque colonies were recovered by roll tube technique as by the conventional anaerobic technique. With the MM 10 roll tube technique, 7 d of incubation revealed only 93% of the colonies that could be detected after 14 d of incubation.


The influence of the organic matrix on demineralization of bovine root dentin in vitro.
The effect of matrix degradation on the rate of demineralization of dentin lesions was investigated. It was hypothesized that the demineralized matrix would inhibit the demineralization of the underlying mineralized dentin. Bovine root dentin specimens were alternately demineralized and incubated with either a bacterial collagenase or buffer (control). The demineralization was carried out under various conditions: Acetic acid solutions were used to form incipient and advanced erosive lesions, and lactic acid solutions containing a bisphosphonate were used to form incipient subsurface lesions. Under all conditions, the demineralization was found to be accelerated when the matrix was degraded by collagenase. This increase was more pronounced in advanced erosive lesions than in incipient lesions. Microscopic examination of collagenase-treated specimens revealed that the matrix of erosive lesions contained several layers of differently affected matrices, whereas the matrix of subsurface lesions appeared to be equally affected throughout the lesion. In conclusion, the matrix degradation was different in erosive and subsurface lesions but promoted the demineralization in both types of lesions.


Activity of trigeminothalamic neurons in medullary dorsal horn of awake monkeys trained in a thermal discrimination task.
We analyzed the activity of 51 trigeminothalamic neurons in the medullary dorsal horn (trigeminal nucleus caudalis) of monkeys during the performance of behavioral tasks requiring the monkeys to discriminate innocuous and noxious thermal stimuli applied to the face and to detect the onset of visual stimuli. Static properties of trigeminothalamic neurons in behaving monkeys were similar to those in anesthetized monkeys. Responses to passively presented mechanical and thermal stimuli, receptive-field properties, and conduction velocities did not differ in the awake and anesthetized states. For most wide dynamic range and nociceptive-specific trigeminothalamic neurons, there was a negative correlation between the magnitude of thermally evoked activity and behavioral latencies to discriminate 47 and 49 degrees C stimuli. Thus, both groups of neurons provide information that could be used by the monkey to discriminate noxious thermal stimuli. The magnitude of thermal responses of trigeminothalamic neurons was modulated by the behavioral significance of the stimulus. Behaviorally relevant thermal stimuli presented during the thermal discrimination task produced a greater neuronal response than equivalent irrelevant thermal stimuli presented between behavioral trials or presented while the monkey performed the visual detection task. Neurons whose activity is modulated by behavioral state are likely to be involved in discrimination of thermal stimuli, since the activity of these neurons correlates with the behavioral response to the stimuli and information from the modulated neurons is sent to the thalamus. Some trigeminothalamic neurons that exhibited somatosensory responses also responded to behaviorally relevant stimuli and events associated with trial initiation and receipt of reward in the behavioral tasks. Similar events outside a behavioral task evoked no neuronal responses. These task-related responses were similar to those described previously for medullary dorsal horn neurons not identified as to projection sites (14).(ABSTRACT TRUNCATED AT 400 WORDS)


Toxicological evaluation of chemical mixtures.
This paper addresses major developments in the safety evaluation of chemical mixtures during the past 15 years, reviews today's state of the art of mixture toxicology, and discusses challenges ahead. Well-thought-out tailor-made mechanistic and empirical designs for studying the toxicity of mixtures have gradually substituted trial-and-error approaches, improving the insight into the testability of joint action and interaction of constituents of mixtures. The acquired knowledge has successfully been used to evaluate the safety of combined exposures and complex mixtures such as, for example, the atmosphere at hazardous waste sites, drinking water disinfection by-products, natural flavouring complexes, and the combined intake of food additives. To consolidate the scientific foundation of mixture toxicology, studies are in progress to revisit the biological concepts and mathematics underlying formulas for low-dose extrapolation and risk assessment of chemical mixtures. Conspicuous developments include the production of new computer programs applicable to mixture research (CombiTool, BioMol, Reaction Network Modelling), the application of functional genomics and proteomics to mixture studies, the use of nano-optochemical sensors for in vivo imaging of physiological processes in cells, and the application of optical sensor micro- and nano-arrays for complex sample analysis. Clearly, the input of theoretical biologists, biomathematicians and bioengineers in mixture toxicology is essential for the development of this challenging branch of toxicology into a scientific subdiscipline of full value.


Co-existence of lichen amyloidosus and angiolymphoid hyperplasia with eosinophilia.
Summary Angiolymphoid hyperplasia with eosinophilia (ALHE) is an uncommon benign vascular tumour. It presents with small, dull red papules or nodules usually on the ears and preauricular areas and only 20% of lesions are multiple. We report a case of multiple scattered lesions of ALHE in a patient who subsequently developed lichen amyloidosus. Cases of lichen amyloidosus in association with Kimura's disease have been reported previously, but there are no reports of lichen amyloidosus with ALHE. The coexistence of these two conditions implies that ALHE is an inflammatory disorder, as an inflammatory process resulting in basal layer damage is necessary for the occurrence of lichen amyloidosus.