Engraftment and differentiation of human metanephroi into functional mature nephrons after transplantation into mice is accompanied by a profile of gene expression similar to normal human kidney development.
Metanephroi, the embryonic precursors of the adult kidney, can be induced in vivo to grow and develop. Despite their potential clinical utility for transplantation, the ability of human metanephroi to differentiate after transplantation into functional mature nephrons is mostly unknown. To address this, 70-d human metanephroi were transplanted into NOD/SCID mice; global gene expression patterns that underlie development of human metanephric transplants were analyzed and compared with normal human kidney development. In addition, functionality of the grafts was assessed by dimercaptosuccinic acid radioisotope scans at different times after transplantation. The results of hybridization to cDNA arrays when RNA was derived from normal human kidneys at 8, 12, 16, and 20 wk gestation demonstrated that a subset of 240 genes changed substantially with time. The induced genes can be classified as cell cycle regulators, transcription and growth factors, and signaling, transport, adhesion, and extracellular matrix molecules. Strikingly, clustering analysis of global gene expression at 2, 6, and 10 wk after metanephric transplantation revealed an expression profile that characterizes normal human kidney development. Moreover, maturation of the transplants was accompanied by an increased uptake of dimercaptosuccinic acid. Nevertheless, expression levels of specific genes were mostly found to be suppressed in the transplants compared with the normal kidneys. These data provide insights into human kidney development and support the possibility of the transplantability of human metanephroi. Understanding of the molecular regulation of the transplanted developing metanephroi might lead to the development of strategies aimed at increasing the levels of specific genes, nephron endowment, and graft function.


Abraham Flexner's "mooted question" and the story of integration.
Contemporary medicine is characterized by dualities. They include psyche and soma, subject and object, and, most important, science and humanism. The authors, in exploring Flexner's landmark publication, suggest that the history of curricular evolution has been marked by a quest for the integration of two knowledge bases: science and clinical medicine. They describe this goal as a preoccupation of medical educators, arguing that it was triggered, in part, by Flexner's recommendation for a two-phase curriculum. Their claim is illustrated with an analysis of motives for curricular renewal at one medical school and a review of published reports from educational opinion leaders. They discuss Flexner's conception of integration-namely, that unity could be achieved through methodology and, in particular, through inductive reasoning. They situate this perspective in the context of other purported integrative principles such as bioethics, narrative medicine, and the biopsychosocial model. They conclude by recommending an alternative framework for integration. The authors propose that a synthesis of two separate knowledge domains can be achieved through a common purpose and that, in a clinical context, that purpose is the well-being of the patient. Well-being is defined as the patient's ability to pursue achievable goals and purposes. It can be brought about by changing medicine's emphasis from the eradication of disease to the restoration of functions impaired by sickness. This idea is congruent with aspects of Flexner's understanding of medical practice, as shown in his statement that the restoration of normal functioning should be the doctor's "goal in action."


Purification and characterization of lysozyme-pregnanediol glucuronide conjugates: the effect of the hapten and coupling reagent on the substitution level, sites of acylation and the consequences for the development of future immunoassays.
The preparation of conjugates destined for use in homogeneous enzyme immunoassays requires careful control to maximize the yield of conjugate, limit the level of substitution and obtain highly inhibitable conjugates. Furthermore, previous studies have shown that the acylation position and orientation of haptens in enzyme conjugates is important in determining the recognition and strength of binding of the hapten by anti-hapten antibodies. In this study we have prepared and purified pregnanediol glucuronide conjugates of hen egg white lysozyme by the active ester and mixed anhydride methods and compared the resulting conjugates with those obtained when conjugating with oestrone glucuronide. Conjugation of lysozyme with pregnanediol glucuronide by the mixed anhydride procedure resulted in two major derivatives monoacylated at lysine residues 33 and 97, while acylation by the active ester procedure resulted in six major derivatives acylated at one or more of lysine residues 33, 97 and 116. Comparison of these conjugates with oestrone glucuronide conjugates suggested that when using the more reactive active ester method the protein environment of the amino groups and the acylating agent directed the site(s) of acylation and level of substitution. However, in the case of the less reactive mixed anhydride coupling procedure the chemical nature of the hapten also influenced the final conjugation product makeup. These findings have implications for the design of new, highly inhibitable enzyme conjugate immunoassay systems.


Comparison of antiplatelet effects of prasugrel and ticagrelor in cynomolgus monkeys by an ELISA-based VASP phosphorylation assay and platelet aggregation.
Prasugrel is the third generation thienopyridine prodrug, and ticagrelor is a non-competitive direct acting P2Y12 antagonist. In phase 3 studies, both agents reduced ischaemic event rates compared to clopidogrel. The present in vitro human and monkey studies showed that ticagrelor's active metabolite (AM) was more potent than ticagrelor and prasugrel's AM on inhibition of ADP-induced platelet aggregation by light transmission aggregometry and ELISA-based vasodilator-stimulated phosphoprotein (VASP) phosphorylation assay. In contrast, on an oral dosage basis (mg/kg), prasugrel showed more potent platelet inhibition compared to ticagrelor on ex vivo aggregation and VASP phosphorylation assays in monkeys. Single oral doses of prasugrel (0.3 and 1 mg/kg) resulted in robust antiplatelet effects, which were sustained up to 24 hours after administration. Ticagrelor (3 and 10 mg/kg, p.o.) also showed significant antiplatelet effects but its effects were diminished at 24 hours after the dosing. Repeat administration of prasugrel (1.8 mg/kg loading dose [LD], 0.3 mg/kg once daily maintenance dose [MD]) showed more rapid antiplatelet effects and longer duration of action throughout the entire day. Twice a day repeat administration of ticagrelor (10 mg/kg bid MD following a single 20 mg/kg LD) also showed significant antiplatelet effects but with more intra-day variability compared to prasugrel. The in vitro and ex vivo studies showed strong correlations between platelet aggregation and VASP phosphorylation for prasugrel, ticagrelor and their AMs. These strong correlations between platelet aggregation and VASP phosphorylation in non-human primates also suggest that ELISA-based human VASP assay can be utilised for non-human primate platelet studies.


Male pronuclear formation and sperm mitochondria in porcine oocytes following intracytoplasmic injection of pig or mouse sperm.
In the present study we determined the chromatin organization and fate of introduced mitochondria in porcine embryos following intracytoplasmic injection of pig or mouse sperm cells. At 3, 6, 9 and 12 h following injection of pig or mouse spermatozoa or isolated sperm heads, the oocytes were fixed and stained with propidium iodide. Between 3 and 6 h following injection, both porcine and murine sperm chromatin developed into pronuclei. The male and female pronuclei were apposed within 12 h in porcine oocytes following sperm injection from either source. We also introduced foreign mitochondria from either mouse or pig sperm midpiece into porcine oocytes following sperm injection. While porcine sperm mitochondria rapidly disappeared from the actively developing porcine oocytes, mouse sperm mitochondria remained in the embryos until the 8-cell stage. These results suggest that pronuclear formation and movement occur between 6 and 12 h following sperm incorporation into the cytoplasm, and that foreign mitochondria are selectively removed in a species-specific manner.


Tridimensional Matryoshka Tattoo: An Important.
Dear Editor, Tattooing is a global and ancient practice that has endured until the present day. It was originally used to indicate religious beliefs, tribal affiliation, loyalty to a leader, or had a therapeutic function. Adverse reactions from tattooing are common, and cutaneous reactions to red pigment have been widely reported (1,2). Herein we report a case of a 30-year-old female patient admitted to our Department of Dermatology for a reaction to a tattoo localized at the violet and black areas of the tattoo on the upper part of her left leg. The patient reported that the tattoo had been made two years earlier, but the cutaneous alterations appeared after she decided to change the color from pink to violet. On physical examination, multiple erythematous nodular itching lesions were present at the areas of the tattoo in which the violet and black color were used (Figure 1). She had undergone antibiotic therapy without resolution after which topical corticosteroids were applied with temporary remission of signs and symptoms. Personal and familial medical history were negative. The patient reported a jewelry allergy that had never been investigated. Based on the suspicion of an allergic reaction we decided to execute a patch test SIDAPA series and patch test special tattoo series (copper sulfate 1% water, dimetilaminoazobenzene-p 1%, aminoazotoluene-o 1%, blue scattered 3 1%, blue scattered 124 1%, yellow scattered 3 1%, orange scattered 3 1%, red scattered 1 1%, gentian violet 2%, cadmium chloride 1% in water, nickel sulphate 5%, iron chloride 2% in water, potassium dichromate 0.5%, chromium trichloride 2%, aminoazobenzene-p 0.25%, cobalt chloride 1%, aluminum chloride 2%, titanium dioxide 0.1%, zinc 2.5%, mercury chloride 0.05% in water, kathon cg 0.01% in water, phenol 0.5%, ethylenediamine hydrochloride1%, phenylenediamine base-p 1%, formaldehyde 1% in water, phthalic anhydride 1%, rosin 20%, dibutyl phthalate 5%, hexamethylenetetramine 1%, benzophenone 5%). Both series of patch test showed positivity for nickel sulfate 5% at 48 hours (++) and 72 hours (+++). We then performed a 4 mm punch biopsy of the nodular lesions localized at the black and violet areas. The histological examination revealed dermal sclerosis characterized by inflammatory reaction with lympho-mononuclear infiltration in the perivasal zone. Macrophages with red and black pigment were present. The histological pattern was compatible with a granulomatous reaction. Tattooing can result in a wide variety of complications, whose prevalence and incidence still remain unclear. Some authors (3) classify such cutaneous complications in various ways, such as according to: - the length of their evolution: acute and chronic reactions; - the delay of onset after tattooing: early - during the healing phase - or delayed - after tattoo healing; - the type of reaction: infection, hypersensitivity reaction, etc. The practice of tattooing may have local or systemic complications. Dermatoses such as psoriasis, systemic erythematous lupus, sarcoidosis, lichen planus, and pseudo-epitheliomatous hyperplasia can be localized in the area of the tattoo, but allergic sensitivity to one of the pigments is the most frequent cause of dermatological reactions in the site of tattoo (4,5). In fact, adverse reactions to tattoo pigments, especially the red one, are well-described in literature. Furthermore, these compounds frequently contain components which are not systematically characterized. In our case, the granulomatous reaction did not correspond to an allergic reaction to the pigment. In fact, the patch test was negative for all pigments investigated, only showing a positive result for nickel sulfate. However, the specific and well-defined localization of the nodular lesions on the black and violet areas led us to hypothesize that the tattoo pigments in these areas contained some unknown component causing the reaction. In our opinion, a possible explanation could be that the new pigment that had been used contained a small amount of nickel sulfate, which caused the granulomatous reaction. In conclusion, we presented this clinical case to emphasize the widespread incidence of tattoo-related adverse effects, which are mostly caused by red pigment. Dermatologists should constantly strive familiarize themselves with current research on this practice and its complications. On the other hand, people with potential risk factors for adverse reactions should refer to a specialist before getting tattoos. Tattooists should use a checklist and informed consent to screen people with such potential risk factors. Furthermore, it is necessary to perform additional studies concerning ink and pigment components, with the aim of systemically characterizing the substances used in tattoos. Lastly, as emphasized by our case, patients at risk should referred to the dermatologist not only before getting a new tattoo but also in case of color changes in a pre-existing tattoo.


Hemocyanin gene family evolution in spiders (Araneae), with implications for phylogenetic relationships and divergence times in the infraorder Mygalomorphae.
Hemocyanins are multimeric copper-containing hemolymph proteins involved in oxygen binding and transport in all major arthropod lineages. Most arachnids have seven primary subunits (encoded by paralogous genes a-g), which combine to form a 24-mer (4×6) quaternary structure. Within some spider lineages, however, hemocyanin evolution has been a dynamic process with extensive paralog duplication and loss. We have obtained hemocyanin gene sequences from numerous representatives of the spider infraorders Mygalomorphae and Araneomorphae in order to infer the evolution of the hemocyanin gene family and estimate spider relationships using these conserved loci. Our hemocyanin gene tree is largely consistent with the previous hypotheses of paralog relationships based on immunological studies, but reveals some discrepancies in which paralog types have been lost or duplicated in specific spider lineages. Analyses of concatenated hemocyanin sequences resolved deep nodes in the spider phylogeny and recovered a number of clades that are supported by other molecular studies, particularly for mygalomorph taxa. The concatenated data set is also used to estimate dates of higher-level spider divergences and suggests that the diversification of extant mygalomorphs preceded that of extant araneomorphs. Spiders are diverse in behavior and respiratory morphology, and our results are beneficial for comparative analyses of spider respiration. Lastly, the conserved hemocyanin sequences allow for the inference of spider relationships and ancient divergence dates.


Serum levels of perfluoroalkyl substances (PFAS) and body composition - A cross-sectional study in a middle-aged population.
It has been suggested that per- and polyfluoroalkyl substances (PFAS) are endocrine disruptors with a potential to influence fat mass. The primary hypothesis tested was that we would find positive relationships for PFAS vs measures of adiposity. In 321 subjects all aged 50 years in the POEM study, five PFAS (perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA)) were measured in serum together with a Dual-energy X-ray absorptiometry (DXA) scan for determination of fat and lean mass. Whole-body magnetic resonance imaging scan was performed and the body was divided into >1 million voxels. Voxel-wise statistical analysis was carried out by a novel method denoted Imiomics. PFOS and PFHxS, did not show any consistent associations with body composition. However, PFOA, and especially PFNA and PFDA, levels were inversely related to most traditional measures reflecting the amount of fat in women, but not in men. In the Imiomics analysis of tissue volume, PFDA and PFNA levels were inversely related to the volume of subcutaneous fat, mainly in the arm, trunk and hip regions in women, while no such clear relationship was seen in men. Also, the visceral fat content of the liver, the pericardium, and the gluteus muscle were inversely related to PFDA and PFNA in women. Contrary to our hypothesis, some PFAS showed inverse relationships vs measurements of adiposity. PFOS and PFHxS levels in plasma did not show any consistent associations with body composition, but PFOA, and especially PFNA and PFDA were inversely related to multiple measures reflecting the amount of fat, but in women only.


Energy Transfer Dynamics of Formate Decomposition on Cu(110).
Energy transfer dynamics of formate (HCOOa ) decomposition on a Cu(110) surface has been studied by measuring the angle-resolved intensity and translational energy distributions of CO2 emitted from the surface in a steady-state reaction of HCOOH and O2 . The angular distribution of CO2 shows a sharp collimation with the direction perpendicular to the surface, as represented by cosn θ (n=6). The mean translational energy of CO2 is measured to be as low as 100 meV and is independent of the surface temperature (Ts ). These results clearly indicate that the decomposition of formate is a thermal non-equilibrium process in which a large amount of energy released by the decomposition reaction of formate is transformed into the internal energies of CO2 molecules. The thermal non-equilibrium features observed in the dynamics of formate decomposition support the proposed Eley-Rideal (ER)-type mechanism for formate synthesis on copper catalysts.


Inspiratory capacity and decrease in lung hyperinflation with albuterol in COPD.
Inspiratory capacity (IC) has been proposed as a simple method to assess acute changes in functional residual capacity (FRC) with bronchodilation, assuming that total lung capacity (TLC) is unchanged. This assumption is based on studies using body plethysmography, which may not accurately measure TLC in severely obstructed subjects. The aim of this study is to validate the use of IC measured by optoelectronic plethysmography (OEP) [ICOEP], a noninvasive technique capable of computing changes in absolute lung volumes with great accuracy. MEWTHODS AND MEASUREMENTS: We studied 13 subjects with COPD in clinically stable condition at baseline and after 200 microg of inhaled albuterol. Changes in lung volumes were obtained from changes in chest wall volume (Vcw) measured by OEP and were compared with those measured by standard techniques. Albuterol treatment caused a small but significant increase in FEV(1) and FVC, a significant decrease of Vcw at FRC (VcwFRC), but no changes of Vcw at TLC (VcwTLC) and breathing pattern variables. The reduction of VcwFRC was not correlated with either spirometric or breathing-pattern variables. IC measured with a pneumotachograph was highly correlated with and not significantly different from ICOEP (p < 0.001). A single dose of inhaled albuterol does not significantly modify VcwTLC in subjects with COPD, thus validating the use of IC to measure changes of FRC in the assessment of reversibility of airway obstruction.


The potential for floral evolution in response to competing selection pressures following the loss of hawkmoth pollination in Ruellia humilis.
In the absence of hawkmoth pollinators, chasmogamous (CH) flowers of Ruellia humilis self-pollinate by two secondary mechanisms. Other floral visitors might exert selection on CH floral traits to restore outcrossing, but at the same time preferential predation of CH seeds generates selection to increase the allocation of resources to cleistogamous (CL) flowers. To assess the potential for an evolutionary response to these competing selection pressures, we estimated additive genetic variances ( σ A 2 ${\sigma }_{{\rm{A}}}^{2}$ ) and covariances for 14 reproductive traits and three fitness components in a Missouri population lacking hawkmoth pollinators. We found significant σ A 2 ${\sigma }_{{\rm{A}}}^{2}$ for all 11 floral traits and two measures of resource allocation to CL flowers, indicating the potential for a short-term response to selection on most reproductive traits. Selection generated by seed predators is predicted to increase the percentage of CL flowers by 0.24% per generation, and mean stigma-anther separation is predicted to decrease as a correlated response, increasing the fraction of plants that engage in prior selfing. However, the initial response to this selection is opposed by strong directional dominance. The predicted evolutionary decrease in the number of CH flowers available for potential outcrossing, combined with the apparent preclusion of potential diurnal pollinators by the pollen-harvesting activities of sweat bees, suggest that 100% cleistogamy is the likely outcome of evolution in the absence of hawkmoths. However, rare mutations with large effects, such as delaying budbreak until after sunrise, could provide pathways for the restoration of outcrossing that are not reachable by gradual quantitative-genetic evolution.


[Arthroscopic diagnosis and treatment of posttraumatic chronic ankle pain].
To evaluate the arthroscopic diagnosis and treatment of the chronic ankle pain after injury. From April 1999 to June 2008, 39 patients with posttraumatic chronic ankle pain were treated. The mean duration between the initial injury and treatment was 18 months (2 months to 11 years). There were 15 males and 24 females with a mean age of 32 years (15 to 58 years). All the patients were treated with arthroscopic debridement. The preoperative and postoperative ankle functions were evaluated by the AOFAS (the American Orthopaedic Foot and Ankle Society) Clinical Rating System for the ankle-hindfoot. Twenty-six patients had osteochondral lesions. Impingement syndrome in ankle was observed in 21 patients. The impingement tissue included synovial hypertrophy in 3 patients, ligament injury in 10 patients (7 patients had anterior talofibular ligament injury and 3 patients had anteroinferior tibiofibular ligament injury), meniscoid tissue in 6 patients, pathological labrum in 3 patients. All the patients were followed up with an average of (14.2+/-8.4) months (ranged from 5 to 36 months). The AOFAS scores increased significantly from pre-operative (59.7+/-16.9) to post-operative (68.8+/-21.2), and it was obvious in relieving pain, which was pre-operative (22.8+/-10.0) and post-operative (29.5+/-12.1). Arthroscopy can be used to diagnose the cause of chronic ankle pain after injury. Furthermore, arthroscopic debridement was useful to relieve the pain and improve the joint function, and it is appropriate for patients who had no fractures and dislocations.


Retaliatory killing negatively affects African lion (Panthera leo) male coalitions in the Tarangire-Manyara Ecosystem, Tanzania.
In landscapes where people and lions coexist, conflicts are common due to livestock predation and threats to human safety. Retaliatory lion killing by humans is often a consequence and is one of the leading causes of lion population declines across Africa. We assessed the effects of retaliatory lion killing on male lion coalitions in the Tarangire-Manyara Ecosystem (TME) using a long-term dataset of lion monitoring for ten lion prides, spanning over a fourteen year-period from 2004-2018. We also interviewed 214 respondents about their attitudes and awareness of the effects of retaliatory killing on lions. We found that male lion coalitions were larger and lasted for a longer tenure period in locations with low risk of retaliatory killing, as well as far away from active hunting blocks. Further, young people (18-35 years old) had a more positive attitude towards lion existence and conservation compared to older age classes. Surprisingly, people with primary or secondary level of education were more likely to having lions killed if they attack livestock compared to people with no formal education, although the former supported lion presence for tourism in protected areas. We conclude that retaliatory killing has a large effect on long-term lion coalition dynamics and, thus, survival. Community awareness on retaliation effect varies widely, and we recommend implementing better education and policy strategies at TME to protect the declining carnivore populations.


Intracerebral hemorrhage: effective therapy at last?
After decades of relative neglect, the past few years have been particularly eventful for clinical research into spontaneous intracerebral hemorrhage (ICH). Most importantly, we have seen completion of the first large randomized trial of surgical clot evacuation for supratentorial ICH, and also the first trial to demonstrate the efficacy of systemic recombinant factor 7 to stop parenchymal bleeding and prevent clinical worsening. Other important advances include new insights into risk factors, diagnostic imaging, pathophysiology of cellular injury, brain edema and blood flow, blood pressure management, aspiration of parenchymal and intraventricular clots; stem cell therapy, and outcome. Taken together, the impressive scope and progress of ongoing clinical and basic research demonstrate that there is no longer a place for nihilism in the approach to ICH.


Thermal effects of laser stapedectomy in an animal model: CO2 versus KTP.
Although use of the laser for stapedectomy has become common in recent years, controversy remains regarding whether the CO2 or visible-spectrum lasers (argon and KTP) are best suited for this operation. The main concern has been the potential for thermal injury to the inner ear with the visible-spectrum lasers attributable to their absorption characteristics. To further investigate this issue, the author performed 20 laser stapedectomies on adult chinchillas. Following placement of a 0.127-mm-diameter copper/constantan thermocouple (sampling at 12 Hz) beneath the footplate on the medial wall of the vestibule via a distant fenestration site, thermal changes with a micromanipulator-based CO2 and fiberoptic KTP system were compared. This was the first live animal model comparison of these two lasers. There was no statistical difference in the mean temperature elevation between the two systems (P = 0.395).


Purification, characterization, and inhibition of peptide deformylase from Escherichia coli.
Peptide deformylase (EC 188.8.131.52) catalyzes the removal of a formyl group from the N-termini of nascent ribosome-synthesized polypeptides, an obligatory step during protein maturation in eubacteria. Since its discovery in crude Escherichia coli extracts 3 decades ago, the deformylase has resisted all attempts of purification or characterization due to its extraordinary lability. By placing the coding sequence (def gene) of Escherichia coli deformylase behind a bacteriophage T7 promoter, we have, however, been able to overexpress this deformylase in Escherichia coli. Overproduction has allowed the purification of > 50 mg of deformylase enzyme from each liter of cell culture. Purified deformylase is highly active toward N-formylated peptide substrates. A new, sensitive assay for the deformylase has been developed by measuring the amount of released formate using a formate dehydrogenase. This has allowed for the assessment of the catalytic properties of peptide deformylase using a series of synthetic N-formylated peptides as substrates. The deformylase exhibits strong preference for an L-methionine or the isosteric norleucine at the N-terminus of a substrate and has broad specificity for the rest of the residues. Small divalent metal chelators strongly inhibit the E. coli deformylase. In particular, certain 1,2- and 1,3-dithiol compounds act as potent, time-dependent inhibitors of the peptide deformylase.


An improved technique for increasing the accuracy of joint-to-ground distance tracking in kinect v2 for foot-off and foot contact detection.
The Kinect sensor has been widely used in different applications such as rehabilitation and gait analysis. Whilst Kinect v2 was released with several improvements over its predecessor, it still incorporates depth-map intrinsic inaccuracies. This results in inconsistencies in skeletal-data acquisition, especially in joint localisation and distance-to-ground tracking with respect to the Kinect's 3-D Cartesian coordinate reference point. This research proposes a correction technique based on the two-point linear equation derived from the information gathered from different subjects' skeletal data and data regression analysis to compensate the inaccuracies in joint-to-ground data collection. The research also proposes a new footsteps detection method based on skeletal data and plane detection techniques that calculates a footstep by using the ankle's Euclidean distance from the floor, regardless of the subject's distance from the camera. The results show that after the correction technique was applied, data acquisition proved to be consistent and more accurate within a distance range of 1.6-2.9 m from the Kinect camera, regardless of the subject's location to the camera's reference point. Moreover, the inconsistency of joint data read by the Kinect was reduced from 25.69% to 5.25% and the footsteps detection accuracy increased from 42.85% to 79.76% on average for both legs.


Defect Detection of Adhesive Layer of Thermal Insulation Materials Based on Improved Particle Swarm Optimization of ECT.
This paper studies the defect detection problem of adhesive layer of thermal insulation materials. A novel detection method based on an improved particle swarm optimization (PSO) algorithm of Electrical Capacitance Tomography (ECT) is presented. Firstly, a least squares support vector machine is applied for data processing of measured capacitance values. Then, the improved PSO algorithm is proposed and applied for image reconstruction. Finally, some experiments are provided to verify the effectiveness of the proposed method in defect detection for adhesive layer of thermal insulation materials. The performance comparisons demonstrate that the proposed method has higher precision by comparing with traditional ECT algorithms.


Use of chlamydiazyme for the detection of Chlamydia trachomatis in genital infections.
48 endocervical specimens from women with cervicitis and 82 urethral specimens from men with urethritis were investigated for the presence of Chlamydia trachomatis by either the cell culture method or enzyme immunoassay (Chlamydiazyme, Abbott Laboratories). The overall sensitivity and specificity of Chlamydiazyme assay were 84.6% and 95.2% respectively. This study shows that Chlamydiazyme assay is a quite sensitive and specific tool for a rapid and simple detection of chlamydial antigens in genital samples.


Abnormal function of platelet G proteins in long QT syndrome.
Several hypotheses have been proposed for the pathophysiology of the congenital long QT syndrome, however, the underlying mechanism has not yet been elucidated. This study evaluated G protein function in patients with congenital long QT syndrome (LQTS) and compared it with that of normal subjects. Platelet-rich plasma was collected and the cyclic AMP (cAMP) level of platelets was measured in three conditions utilizing radioimmunoassay: the basal state (Basal cAMP), after stimulation by PGE1 (PGE1-cAMP), and after stimulation by PGE1 followed by inhibition by adrenaline (Adr-cAMP), and the results were compared between 7 LQTS patients and 10 healthy volunteers (control). Gs function was defined as (PGE1-cAMP)/(Basal cAMP) and Gi function as ¿(PGE1-cAMP)-(Adr-cAMP)¿/(PGE1-cAMP). Basal cAMP was lower in patients than in the controls: 2.9 +/- 0.6 pmol/ 10(8) cells vs. 4.2 +/- 0.7 pmol/10(8) cells (p < 0.05). The increase in cAMP after PGE1 was similar in the two groups but the peak was lower in the patients: 16.8 +/- 6.2 pmol/10(8) cells vs. 24.8 +/- 7.4 pmol/10(8) cells (PGE1-cAMP). After addition of adrenaline, cAMP decreased to 14.2 +/- 5.8 pmol/10(8) cells vs. 16.2 +/- 7.6 pmol/10(8) cells and the change was significantly smaller in the patients than in the controls: 0.17 +/- 0.12 vs. 0.38 +/- 0.16 (p < 0.05). Basal cAMP was weakly correlated with sinus cycle length (r = -0.48, p > 0.3) and QTc was correlated with Gs function (r = 0.52, p > 0.3) but not with Gi function. Patients with associated Torsade de Pointes had a significantly lower Gi function compared to those without (p < 0.05). In LQTS patients, G protein function was abnormal and the abnormality was associated with clinical characteristics of long QT syndrome. The relationship between the abnormal G protein function and the regulation of the repolarization of the ventricular myocardium needs to be studied further.


Exogenous adenosine triphosphate (ATP) preserves proximal tubule microfilament structure and function in vivo in a maleic acid model of ATP depletion.
The hallmark of ischemic acute renal failure is a rapid and early decline in proximal tubule ATP. Since we have previously shown that over half of apical microfilament losses occur within the first 5 min of experimental ischemic injury, we postulated that microfilament (F-actin) structure and cellular location are dependent on cellular ATP levels. To test this hypothesis, we used maleic acid to selectively inhibit renal cortical ATP production in vivo. Maleic acid significantly decreased tissue ATP and apical F-actin in a dose-dependent manner relative to equimolar sodium chloride controls, yet higher doses of maleic acid quantitatively resulted in net actin polymerization, primarily in the cytoplasm. Functionally, maleic acid decreased glomerular filtration rate (GFR) and tubular reabsorption of sodium (TRNa) in a dose-dependent manner relative to sodium chloride controls. Administration of exogenous ATP resulted in significant increases in tissue ATP, net actin depolymerization, and relocation of F-actin from the cytoplasm back to the apical surface coinciding with increases in GFR and TRNa. Thus, ATP depletion induced by maleic acid resulted in significant cytoskeletal and functional alterations that were ameliorated by exogenous ATP. We therefore conclude that the structure and cellular location of F-actin necessary for normal functioning of proximal tubule cells in vivo is dependent on tissue ATP levels.


[Hypertension and alcohol: central and peripheral mechanisms].
Despite intense research efforts, the etiology of primary hypertension remains ill-defined. During our work on molecular influences of lifestyle factors on hypertension, the question arose to what extent cellular and molecular events could be involved in alcohol-induced hypertension. There is increasing evidence that alcohol initiates central as well as peripheral reactions which in a synergistic manner have a hypertensive action. Thus, alcohol diminishes the baro (presso) reflex by interacting with receptors in the brain stem, i.e. nucleus tractus solitarii and rostral ventrolateral medulla. In addition, alcohol induces an increased sympathetic outflow, most probably linked to secretion of corticotropin-releasing hormone. The increased sympathetic outflow is expected not only to induce adrenoceptor-mediated reactions (vasoconstriction, heart rate increase) but to stimulate oxidation reactions. Deleterious peripheral actions result from acetaldehyde which binds to macromolecules if the abundance of cysteine and glutathione is limited. This acetaldehyde induced reduction of low molecular weight thiol compounds can be interpreted as "oxidative stress" which has various unfavourable consequences. The hypertensive action of alcohol should be taken into account when discussing its potential protective influence on coronary risk.


Emergence of avian influenza A(H7N9) virus causing severe human illness - China, February-April 2013.
On March 29, 2013, the Chinese Center for Disease Control and Prevention completed laboratory confirmation of three human infections with an avian influenza A(H7N9) virus not previously reported in humans. These infections were reported to the World Health Organization (WHO) on March 31, 2013, in accordance with International Health Regulations. The cases involved two adults in Shanghai and one in Anhui Province. All three patients had severe pneumonia, developed acute respiratory distress syndrome (ARDS), and died from their illness. The cases were not epidemiologically linked. The detection of these cases initiated a cascade of activities in China, including diagnostic test development, enhanced surveillance for new cases, and investigations to identify the source(s) of infection. No evidence of sustained human-to-human transmission has been found, and no human cases of H7N9 virus infection have been detected outside China, including the United States. This report summarizes recent findings and recommendations for preparing and responding to potential H7N9 cases in the United States. Clinicians should consider the diagnosis of avian influenza A(H7N9) virus infection in persons with acute respiratory illness and relevant exposure history and should contact their state health departments regarding specimen collection and facilitation of confirmatory testing.


A conserved activation element in BMP signaling during Drosophila development.
The transforming growth factor beta (TGF-beta) family member Decapentaplegic (Dpp) is a key regulator of patterning and growth in Drosophila development. Previous studies have identified a short DNA motif called the silencer element (SE), which recruits a trimeric Smad complex and the repressor Schnurri to downregulate target enhancers upon Dpp signaling. We have now isolated the minimal enhancer of the dad gene and discovered a short motif we termed the activating element (AE). The AE is similar to the SE and recruits the Smad proteins via a conserved mechanism. However, the AE and SE differ at important nucleotide positions. As a consequence, the AE does not recruit Schnurri but rather integrates repressive input by the default repressor Brinker and activating input by the Smad signal transducers Mothers against Dpp (Mad) and Medea via competitive DNA binding. The AE allows the identification of hitherto unknown direct Dpp targets and is functionally conserved in vertebrates.


2-Amino-6-[(2,6-dichloro-phen-yl)imino]-3-oxocyclo-hexa-1,4-dienecarbaldehyde.
The title compound, C(13)H(8)Cl(2)N(2)O(2), was obtained by the oxidation of diclofenac {systematic name: 2-[2-(2,6-dichloro-phenyl-amino)-phen-yl]acetic acid}, an anti-inflammatory drug, with hydrogen peroxide catalysed by chlorido[5,10,15,20-tetra-kis-(2,6-dichloro-phen-yl)porphyrinato]manganese(III), using ammonium acetate as co-catalyst. The asymmetric unit contains two crystallographically independent mol-ecules of the title compound (Z' = 2). The close packing of individual mol-ecules is mediated by a series of strong and rather directional N-H⋯Cl and N-H⋯O hydrogen bonds, plus weak π-π [distance between the individual double bonds of symmetry-related imino-quinone rings = 3.7604 (13) Å] and Cl⋯O inter-actions [3.0287 (18) Å].


Role of diffusion-weighted imaging and proton MR spectroscopy in distinguishing between pyogenic brain abscess and necrotic brain tumor.
Brain abscesses and brain tumors may have similar clinical presentations. For example, only 50% brain abscess patients have fever, which could be masked by corticosteroid therapy. Also, the differential diagnosis of brain abscesses versus cystic or necrotic tumors may be difficult based on computed tomography (CT) or magnetic resonance (MR) imaging findings. However, the strategies of management for abscess and neoplasm are very different, and it is especially imperative to have a correct diagnosis before any surgical intervention of cystic brain lesions. The MR special techniques, e.g. diffusion-weighted imaging (DWI) and proton (1H) MR spectroscopy, are useful as additional diagnostic modalities for differentiating brain abscesses from cystic or necrotic brain tumors. DWI shows high signal intensity in most cases of pyogenic abscesses and low signal intensity in most cases of cystic or necrotic tumors. MR spectroscopy shows characteristic metabolites in pyogenic abscesses, distinct from those in cystic or necrotic tumors.


Relationship between plasma concentrations and cardiac beta-adrenoceptor blockade--a study with oral and intravenous bopindolol.
Bopindolol, an esterified beta-adrenoceptor blocking drug, was administered to nine healthy male volunteers in oral (1 mg and 4 mg) and intravenous (1 mg) doses. Plasma concentrations determined using a radio-receptor assay (RRA) and high pressure liquid chromatography (h.p.l.c.) yielded almost identical results, indicating that hydrolysed bopindolol, the major metabolite, is responsible for the pharmacological activity of the drug. After intravenous administration the half-life for the formation of the hydrolysis product was about 0.3 h. The elimination of hydrolysed bopindolol from the plasma, determined with a one-compartment model occurred with a half-life of about 4 h. There were indications for a longer beta phase of elimination with a half-life of about 8 h, which, owing to the relative insensitivity of the method for concentrations present after more than 24 h, could not be determined exactly. The absolute bioavailability of the active compound is about 70%. Cardiac beta-adrenoceptor blockade was determined as the reduction in exercise-induced tachycardia. With oral doses the maximum effect was reached after 3 h (-29 beats min-1 after 1 mg, -40 beats min-1 after 4 mg). After intravenous administration most of the effect was present after 0.5 h but the maximum effect (-33 beats min-1) was only reached at 3 h. Bopindolol possesses a long duration of action: after 48 h 33% of the maximum effect of the oral dose of 4 mg was still present.(ABSTRACT TRUNCATED AT 250 WORDS)


Mechanisms of immune suppression for CD8+ T cells by human corneal endothelial cells via membrane-bound TGFbeta.
To determine whether CD8(+) T cells in vitro are suppressed or converted into regulators (Treg cells) by human corneal endothelial (HCE) cells. HCE cell lines were established from primary HCE cells, and allogeneic CD8(+) T cells were isolated from peripheral blood mononuclear cells of healthy donors. T-cell activation was assessed for proliferation by [(3)H]-thymidine incorporation. Expression of TGFbeta on HCE cells was evaluated by flow cytometry, RT-PCR, and immunohistochemistry. Anti-TGFbeta-neutralizing antibodies or TGFbeta siRNA was used to abolish the HCE-mediated inhibitory function. CD8(+) T cells exposed to HCE cells were used as Treg cells, to induce Treg cells in vitro by exposure to HCE cells. Expression of CD25 or Foxp3 on Treg cells was evaluated by flow cytometry. Cultured HCE cells produced the membrane-bound active TGFbeta isoform 2. HCE surface TGFbeta2 was necessary, to inhibit CD8(+) T-cell activation via direct cell contact. In addition, although HCE cells were found to constitutively express costimulatory molecules, such as programmed death-ligand 1 (PD-L1) and PD-L2, and secreted thrombosponsin-1, only membrane-bound TGFbeta2 was actually delivered to the CD8(+) T cells. HCE cells were also found to convert some CD8(+) T-cell populations into Treg cells via their membrane-bound TGFbeta. These HCE-induced Treg cells produced soluble forms of TGFbeta1, but not of TGFbeta2, and they also acquired a regulatory phenotype that expressed CD25(high) and Foxp3. Ocular resident tissue-exposed T cells can be suppressed or induced to become regulators within the human peripheral microenvironment.


Discovery of carbon-based strongest and hardest amorphous material.
Carbon is one of the most fascinating elements due to its structurally diverse allotropic forms stemming from its bonding varieties (sp, sp 2 and sp 3). Exploring new forms of carbon has been the eternal theme of scientific research. Herein, we report on amorphous (AM) carbon materials with a high fraction of sp 3 bonding recovered from compression of fullerene C60 under high pressure and high temperature, previously unexplored. Analysis of photoluminescence and absorption spectra demonstrates that they are semiconducting with a bandgap range of 1.5-2.2 eV, comparable to that of widely used AM silicon. Comprehensive mechanical tests demonstrate that synthesized AM-III carbon is the hardest and strongest AM material known to date, and can scratch diamond crystal and approach its strength. The produced AM carbon materials combine outstanding mechanical and electronic properties, and may potentially be used in photovoltaic applications that require ultrahigh strength and wear resistance.


Recent advances in the pathology of alcoholic myopathy.
This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The chairs were Victor R. Preedy and Junko Adachi. The presentations were (1) Alcoholic myopathy: Past, present and future, by Timothy J. Peters and Victor R. Preedy; (2) Protein adducts in the type I and II fiber-predominant muscles of the ethanol-fed rat, by Simon Worrall, Seppo Parkkila, and Onni Niemela; (3) Hydroperoxides and changes in alcoholic myopathy, by Junko Adachi, Migiwa Asamo, and Yasuhino Ueno; and (4) A close association between testicular atrophy, muscle atrophy, and the increase in protein catabolism after chronic ethanol administration, by Kunihiko Takeda, Masayoshi Yamauchi, Kazuhiko Sakamoto, Masaru Takagi, Hisato Nakajima, and Gotaro Toda.


Sox2 is involved in paclitaxel resistance of the prostate cancer cell line PC-3 via the PI3K/Akt pathway.
Prostate cancer is the most commonly diagnosed type of cancer and the second leading cause of cancer‑associated mortality in males. The efficacy of prostate cancer chemotherapy is frequently impaired by drug resistance; however, the underlying mechanisms of this resistance remain elusive. Sex determining region Y-box 2 (Sox2) is of vital importance in the regulation of stem cell proliferation and carcinogenesis. In the present study, using MTT, clone formation, cell cycle and apoptosis assays, over-expression of Sox2 was demonstrated to enhance the paclitaxel (Pac) resistance of the PC-3 prostate cancer cell line, promoting cell proliferation and exhibiting an anti‑apoptotic effect. Western blot analysis revealed that the phosphoinositide 3-kinase/Akt signaling pathway was activated in cells overexpressing Sox2, and by targeting cyclin E and survivin, Sox2 promoted G1/S phase transition and prevented apoptosis under Pac treatment. The present study provided an understanding of Pac resistance in prostate cancer and may indicate novel therapeutic methods for chemoresistant prostate cancer.


The B-MaP-C study: Breast cancer management pathways during the COVID-19 pandemic. Study protocol.
Approximately 55,000 women in the United Kingdom are diagnosed with new breast cancer annually. Since emerging in December 2019, SARS-CoV-2 (coronavirus disease 2019, COVID-19) has become a global pandemic, affecting healthcare delivery worldwide. In response to the pandemic, multiple guidelines were issued to assist with rationalising breast cancer care. The primary aim of the B-MaP-C study is to audit and describe breast cancer management of patients newly diagnosed with breast cancer during the COVID-19 pandemic against pre-COVID-19 management practice in the UK. The implications of changes to management will be determined and the impact of a COVID-19 diagnosis on the patient's breast cancer management will be determined. This is a multi-centre collaborative audit of consecutive breast cancer patients undergoing treatment decisions during the acute and recovery phases of the COVID-19 pandemic. All patients with newly diagnosed primary breast cancer, whose treatment was decided in a multidisciplinary meeting from the 16th March 2020, are eligible for inclusion. As this is an audit ethical approval is not required. Each participating centre is required to register the study locally and obtain local governance approvals prior to commencement of data collection. Local audit data will be available to individual participating units for governance purposes. The results of the data analysis will be submitted for publication, as well as disseminated via the ABS newsletter and a webinar. All data will be presented at national and international conferences, circumstances permitting. Each participating centre received local governance audit registration.


Activity-dependent changes in impulse conduction in normal human cutaneous axons.
The present study was undertaken to determine if the axonal hyperpolarization produced by a brief train of impulses would impair neural transmission in cutaneous afferents of normal human subjects (n = 25). To assess changes in axonal excitability, a submaximal test stimulus was conditioned by a train of 10 supramaximal stimuli at 200 Hz. This produced a depression in excitability lasting up to 100 ms, demonstrable at nodes of Ranvier remote from the site of stimulus application, and probably due to activation of a slow K+ conductance. The effects of this change in excitability on neural transmission were assessed using a supramaximal test pulse. This revealed small but significant activity-dependent decreases in amplitude at conditioning-test intervals up to 20 ms and increases in latency at intervals up to 70 ms. Both the amplitude decrease and the latency increase were greater the longer the conduction distance. The reduction in amplitude of the compound sensory potential could be explained by temporal dispersion due to the increase in latency. It is concluded that, at the nodes of normal cutaneous afferents, the safety margin for impulse generation is sufficiently high that the activity-dependent hyperpolarization does not produce conduction block. It is likely that the previously described reductions in the amplitude of the compound sensory action potential in response to brief trains of stimuli were due to dispersion of the volley, not conduction failure, and that conduction failure does not occur in normal cutaneous axons solely by activation of slow K+ conductances.(ABSTRACT TRUNCATED AT 250 WORDS)


The botanist George Gardner and his impressions of slave culture in Brazil: Rio de Janeiro, 1810-1850.
This article analyzes the English botanist George Gardner's trip to Brazil during the 1830s. After graduating from the University of Glasgow Gardner was influenced by his teacher and by readings of contemporary naturalists and set off for Brazil in March of 1836, arriving two months later in Rio de Janeiro. The article presents Gardner's impressions of slavery in Brazil, in an attempt to unveil the symbolic universe of a play he witnessed and described, which took place on a farm in Rio de Janeiro on Christmas night. By describing black slavery in its routes across the Atlantic, we compare this event with other similar happenings in Brazil and in Trinidad and Tobago.


Interpreting global trends in type 2 diabetes complications and mortality.
International trends in traditional diabetes complications (cardiovascular, renal, peripheral vascular, ophthalmic, hepatic or neurological diseases) and mortality rates are poorly characterised. An earlier review of studies published up to 2015 demonstrated that most data come from a dozen high-income countries (HICs) in North America, Europe or the Asia-Pacific region and that, in these countries at least, rates of acute glycaemic fluctuations needing medical attention and amputations, myocardial infarction and mortality were all declining over the period. Here, we provide an updated review of published literature on trends in type 2 diabetes complications and mortality in adults since 2015. We also discuss issues related to data collection, analysis and reporting that have influenced global trends in type 2 diabetes and its complications. We found that most data on trends in type 2 diabetes, its complications and mortality come from a small number of HICs with comprehensive surveillance systems, though at least some low- and middle-income countries (LMICs) from Africa and Latin America are represented in this review. The published data suggest that HICs have experienced declines in cardiovascular complication rates and all-cause mortality in people with diabetes. In parallel, cardiovascular complications and mortality rates in people with diabetes have increased over time in LMICs. However, caution is warranted in interpreting trends from LMICs due to extremely sparse data or data that are not comparable across countries. We noted that approaches to case ascertainment and definitions of complications and mortality (numerators) and type 2 diabetes (the denominator) vary widely and influence the interpretation of international data. We offer four key recommendations to more rigorously document trends in rates of type 2 diabetes complications and mortality, over time and worldwide: (1) increasing investments in data collection systems; (2) standardising case definitions and approaches to ascertainment; (3) strengthening analytical capacity; and (4) developing and implementing structured guidelines for reporting of data.


Time-dependent wave packet simulations of transport through Aharanov-Bohm rings with an embedded quantum dot.
We have performed time-dependent wave packet simulations of realistic Aharonov-Bohm (AB) devices with a quantum dot embedded in one of the arms of the interferometer. The AB ring can function as a measurement device for the intrinsic transmission phase through the quantum dot, however, care has to be taken in analyzing the influence of scattering processes in the junctions of the interferometer arms. We consider a harmonic quantum dot and show how the Darwin-Fock spectrum emerges as a unique pattern in the interference fringes of the AB oscillations.


[Developement of a standardised questionnaire. Specific interventions for people with dementia in long-term care].
Caring for residents in long-term care who suffer from dementia is a special challenge. In the context of a research project a questionnaire for a mail survey in nursing homes was developed in order to describe specific nursing interventions for dementia in daily practice. The Questionnaire development was done according to acknowledged standards for questionnaire development, using means of operationalisation and external expert rating. Then the questionnaire was tested in a two-phase-pretest. Seven nursing homes were involved in a cognitive pretest. The standard-pretest was sent to 200 nursing homes (response rate 17.5 percent). Evaluation of the questionnaire drafts by means of two-phase-pretesting proved to be an effective measure for continuous improvement. The resulting questionnaire should be used to collect data about specific interventions for people suffering from dementia in residential long-term care.


Multicomponent kinetic determinations using artificial neural networks.
Neural networks were successfully used for multicomponent kinetic determinations of species with rate constant ratios approaching unity without the aid of spectral discrimination. The ensuing method relies on two inputs describing the profile of the kinetic curve for each mixture, which is obtained by preprocessing kinetic data using nonlinear least-squares regression. A straightforward network architecture (2:4s:21) was used to resolve mixtures of 2- and 3-chlorophenol; the trained network estimated the concentrations of both components in the mixture with a relative standard error of prediction of approximately 5%, which is much lower than that obtained with Kalman filtering. The effect of some variables such as the rate constant and analyte concentration ratios on the proposed multicomponent determination is discussed.


Copper(II)-selective fluorimetric bulk optode membrane based on a 1-hydroxy-9,10-anthraquinone derivative having two propenyl arms as a neutral fluorogenic ionophore.
A new optical chemical sensor has been developed for the selective determination of copper(II) ions in aqueous solutions. The reversible sensing system was prepared by incorporating 1-hydrpxy-2-(prop-2'-enyl)-4-(prop-2'-enyloxy)-9,10-anthraquinone (AQ) as a neutral Cu2+-selective fluoroionophore in the plasticized PVC membrane with potassium tetrakis(p-chlorophenyl borate) as an anionic additive. The response of the sensor is based on the fluorescence quenching of AQ by Cu2+ ions. At a pH 5.5, the proposed sensor displays a calibration response for Cu2+ over a wide concentration rang of 1.0 x 10(-2) to 1.0 x 10(-6) M, with a relatively fast response of less than 40 s. In addition to high stability and reproducibility, the sensor shows a unique selectivity towards Cu2+ ion with respect to common co-existing cations. The proposed fluorescence optode was applied successfully to the determination of copper(II) in black tea samples.


Phenolic and short-chained aliphatic organic acid constituents of wild oat (Avena fatua L.) seeds.
The objective of this research was to identify and quantify the phenolic and short-chained aliphatic organic acids present in the seeds of three wild-type populations of wild oat and compare these results to the chemical composition of seeds from two commonly utilized wild oat isolines (M73 and SH430). Phenolic acids have been shown to serve as germination inhibitors, as well as protection for seeds from biotic and abiotic stress factors in other species, whereas aliphatic organic acids have been linked to germination traits and protection against pathogens. Wild oat populations were grown under a "common garden" environment to remove maternal variation, and the resulting seeds were extracted to remove the readily soluble and chemically bound phenolic and aliphatic organic acid components. Compounds were identified and quantified using gas chromatography-mass spectrometry. Ferulic and p-coumaric acid comprised 99% of the total phenolic acids present in the seeds, of which 91% were contained in the hulls and 98% were in the chemically bound forms. Smaller quantities of OH benzoic and vanillic acid were also detected. Soluble organic acids concentrations were higher in the M73 isoline compared to SH430, suggesting that these chemical constituents could be related to seed dormancy. Malic, succinic, fumaric and azelaic acid were the dominant aliphatic organic acids detected in all seed and chemical fractions.


Pulmonary alveolar microlithiasis: a case report with emphasis on imaging findings.
Pulmonary alveolar microlithiasis (PAM) is a rare disease characterized by the presence of small calculi in the alveolar space. The authors report a case of a 21-year-old man with a 2-year history of shortness of breath on exertion and dry cough. Physical examination was altered only for crackles at auscultation. Pulmonary function revealed a mild restrictive ventilatory defect and the chest radiograph demonstrated paracardiac confluence of dense micronodular infiltrate. High-resolution CT scan revealed diffuse ground glass attenuation and septal thickening, more pronounced in lower pulmonary regions, with calcifications along the interlobar septa and subpleural regions. A transbronchial lung biopsy confirmed the diagnosis of PAM.


The genetic basis of differential autodiploidization in evolving yeast populations.
Spontaneous whole-genome duplication, or autodiploidization, is a common route to adaptation in experimental evolution of haploid budding yeast populations. The rate at which autodiploids fix in these populations appears to vary across strain backgrounds, but the genetic basis of these differences remains poorly characterized. Here, we show that the frequency of autodiploidization differs dramatically between two closely related laboratory strains of Saccharomyces cerevisiae, BY4741 and W303. To investigate the genetic basis of this difference, we crossed these strains to generate hundreds of unique F1 segregants and tested the tendency of each segregant to autodiplodize across hundreds of generations of laboratory evolution. We find that variants in the SSD1 gene are the primary genetic determinant of differences in autodiploidization. We then used multiple laboratory and wild strains of S. cerevisiae to show that clonal populations of strains with a functional copy of SSD1 autodiploidize more frequently in evolution experiments, while knocking out this gene or replacing it with the W303 allele reduces autodiploidization propensity across all genetic backgrounds tested. These results suggest a potential strategy for modifying rates of spontaneous whole-genome duplications in laboratory evolution experiments in haploid budding yeast. They may also have relevance to other settings in which eukaryotic genome stability plays an important role, such as biomanufacturing and the treatment of pathogenic fungal diseases and cancers.


[Methods of enumeration of bacteria in drinking water].
Methods of the enumeration of total bacteria and Coliform in drinking water were researched in this paper. The differences between heterotrophic plate count and direct viable count method were compared. It is concluded that the total number of bacteria in R2A medium is one order of quantity higher than the traditional plate count agar, and the results of acridine orange direct counts (AODC) is the highest. Some different staining methods in direct viable count were also compared in this paper, such as nalidixic acid, CTC staining and BacLight staining. The proportion of the live bacteria to the dead is about 10%.


Helicobacter pylori and impaired gastric secretory functions associated with duodenal ulcer and atrophic gastritis.
Previous study showed that duodenal ulcer (DU) patients infected with Helicobacter pylori (H. pylori) have increased basal and pentagastrin- or GRP-induced gastric acid secretion and that these disturbances reversed fully after eradication of H. pylori. This study was designed to compare the gastric acid secretory profile, plasma gastrin levels and growth factors (EGF and TGF alpha) expression in gastric mucosa in DU patients with those in atrophic gastritis patients before and six months after verified eradication of H. pylori. In DU patients, basal and stimulated (GRP and pentagastrin) gastric acid secretion was significantly higher than in healthy controls. Six months following the eradication of H. pylori with triple therapy (omeprazole+clarithromycin+amoxicillin), this secretion returned to normal value. In contrast, in patients with atrophic gastritis, such eradication of H. pylori resulted in a significant increase in basal and pentagastrin- and GRP-stimulated acid secretion. Mucosal expression of immunoreactive EGF and TGF alpha was significantly enhanced in H. pylori positive DU and atrophic gastritis patients but this elevation disappeared or was markedly decreased 6 months upon the eradication of H. pylori. We conclude that 1) H. pylori infection is accompanied both in DU and atrophic gastritis patients by an enhanced plasma gastrin and increased mucosal expression of EGF and TGF alpha, 2) basal and GRP-induced acid secretion is significantly elevated in DU, whereas that in atrophic gastritis patients is greatly reduced, and 3) the H. pylori eradication restores gastric acid and plasma gastrin release as well as the mucosal expression of growth factors in DU and atrophic gastritis.


The making of a branching annelid: an analysis of complete mitochondrial genome and ribosomal data of Ramisyllis multicaudata.
Ramisyllis multicaudata is a member of Syllidae (Annelida, Errantia, Phyllodocida) with a remarkable branching body plan. Using a next-generation sequencing approach, the complete mitochondrial genomes of R. multicaudata and Trypanobia sp. are sequenced and analysed, representing the first ones from Syllidae. The gene order in these two syllids does not follow the order proposed as the putative ground pattern in Errantia. The phylogenetic relationships of R. multicaudata are discerned using a phylogenetic approach with the nuclear 18S and the mitochondrial 16S and cox1 genes. Ramisyllis multicaudata is the sister group of a clade containing Trypanobia species. Both genera, Ramisyllis and Trypanobia, together with Parahaplosyllis, Trypanosyllis, Eurysyllis, and Xenosyllis are located in a long branched clade. The long branches are explained by an accelerated mutational rate in the 18S rRNA gene. Using a phylogenetic backbone, we propose a scenario in which the postembryonic addition of segments that occurs in most syllids, their huge diversity of reproductive modes, and their ability to regenerate lost parts, in combination, have provided an evolutionary basis to develop a new branching body pattern as realised in Ramisyllis.


Dural carotid cavernous sinus fistula: ocular characteristics, endovascular management and clinical outcome.
To describe the ocular findings, endovascular treatment, and clinical outcome in patients with dural carotid cavernous sinus fistula (CCF). A retrospective evaluation of 80 consecutive patients who underwent examination and treatment for dural CCF between January 1997 and December 2004 was performed. Fifty females and 30 males, with an average age of 49 years (from 6 -80 years) participated in this study. All patients had more than one clinical signs and symptoms including proptosis (84%), arterialization of conjunctival vein (93%), chemosis (42%), cranial nerve palsy (52%), elevated intraocular pressure (51%), and optic neuropathy (13%). Diminished vision was found in 43% of the patients. The degree of visual deficit ranged from 20/40 to no light perception. After angiographic evaluation, patients were classified to CCF Barrow's type B 14%, type C 15%, and type D 71%. Endovascular treatment by transvenous and/or transarterial embolization was performed in 60 patients (75%). Carotid-angular compression therapy was solely performed in 19 patients (24%) and was used as an adjunct to endovascular treatment in 30 patients (38%). The follow-up period ranged from 6 to 94 months. Clinical cure was achieved in 41 patients (51%) and improvement in 30 patients (38%). Anatomical cure was demonstrated by angiogram in 50 patients (63%). Intra-operative complications were found in three patients including ophthalmic artery occlusion and cerebral infarction. Eight patients experienced transient aggravation of symptoms including increased proptosis, elevation of intraocular pressure, choroidal detachment that required suprachoroidal drainage, and venous stasis retinopathy. Ophthalmic vein thrombosis resulting in central retinal vein occlusion was developed in three patients and finally caused severe visual deficit. There was no operative mortality. Selective management with endovascular therapy and manual compression are the effective treatment for dural CCF. However sight-threatening complications can develop after therapy due to progressive ophthalmic vein thrombosis and should be carefully monitored.


Antibody to E1 peptide of hepatitis C virus genotype 4 inhibits virus binding and entry to HepG2 cells in vitro.
To analyze the neutralizing activity of antibodies against E1 region of hepatitis C virus (HCV). Specific polyclonal antibody was raised via immunization of New Zealand rabbits with a synthetic peptide that had been derived from the E1 region of HCV and was shown to be highly conserved among HCV published genotypes. Hyper-immune HCV E1 antibodies were incubated over night at 4 degree Celsius with serum samples positive for HCV RNA, with viral loads ranging from 615 to 3.2 million IU/ mL. Treated sera were incubated with HepG2 cells for 90 min. Blocking of viral binding and entry into cells by anti E1 antibody were tested by means of RT-PCR and flow cytometry. Direct immunostaining using FITC conjugated E1 antibody followed by Flow cytometric analysis showed reduced mean fluorescence intensity in samples pre-incubated with E1 antibody compared with untreated samples. Furthermore, 13 out of 18 positive sera (72%) showed complete inhibition of infectivity as detected by RT-PCR. In house produced E1 antibody, blocks binding and entry of HCV virion infection to target cells suggesting the involvement of this epitope in virus binding and entry. Isolation of these antibodies that block virus attachment to human cells are useful as therapeutic reagents.


Role of the Pyk2-MAP kinase-cPLA2 signaling pathway in shear-dependent platelet aggregation.
Mechanisms of shear-induced platelet aggregation are not established. Data that ristocetin-induced von Willebrand factor (VWF) binding to glycoprotein (Gp) Ibalpha activates proline-rich tyrosine kinase 2 (Pyk2) and extracellular-regulated kinase (ERK) has led to speculation that these events are coupled and that a MAP kinase may activate cytosolic phospholipase A2 (cPLA2)-mediated arachidonic acid (AA) release. To test this hypothesis and clarify the role of AA metabolism in shear-induced VWF-dependent platelet aggregation, we examined Pyk2, ERK1/2, and p38 phosphorylation, and arachidonic acid release and metabolism in platelets subjected to pathological shear stress in vitro. We observe tyrosine phosphorylation of Pyk2, p38, and ERK1/2 but no measurable increase in free AA, 12-hydroxyeicosatetraenoic acid, or thromboxane A2. Inhibitors of ERK, p38, or cyclooxygenase activation fail to affect shear-induced platelet aggregation. When washed platelets are aspirin-pretreated, arachidonic acid release becomes measurable and aggregation at 60 and 120 s is attenuated. These data indicate that shear-induced VWF binding to platelet GpIb-IX-V activates Pyk2, ERK1/2, p38, and cPLA2, but that the magnitude of these responses is below the threshold needed to enhance shear-induced VWF-dependent platelet aggregation in the presence of plasma. These results provide a mechanistic basis for the long-standing observation that shear-dependent platelet aggregation is unaffected by the antiplatelet drug aspirin.


Computational approaches for skin sensitization prediction.
Drugs, cosmetics, preservatives, fragrances, pesticides, metals, and other chemicals can cause skin sensitization. The ability to predict the skin sensitization potential and potency of substances is therefore of enormous importance to a host of different industries, to customers' and workers' safety. Animal experiments have been the preferred testing method for most risk assessment and regulatory purposes but considerable efforts to replace them with non-animal models and in silico models are ongoing. This review provides a comprehensive overview of the computational approaches and models that have been developed for skin sensitization prediction over the last 10 years. The scope and limitations of rule-based approaches, read-across, linear and nonlinear (quantitative) structure-activity relationship ((Q)SAR) modeling, hybrid or combined approaches, and models integrating computational methods with experimental results are discussed followed by examples of relevant models. Emphasis is placed on models that are accessible to the scientific community, and on model validation. A dedicated section reports on comparative performance assessments of various approaches and models. The review also provides a concise overview of relevant data sources on skin sensitization.


Health-related quality of life in women with fibromyalgia: clinical and psychological factors associated.
The objective of the study was to analyse the impact of fibromyalgia (FM) on health-related quality of life (HRQOL) and to identify clinical and psychological factors associated with the disease. A cross-sectional study was conducted with adult Portuguese women with FM. Analysed data were demographic, clinical and psychological variables and HRQOL: SF-36 and Fibromyalgia Impact Questionnaire (FIQ). The relationship between HRQOL and the other variables was made with a bivariate analysis. To assess the relative contribution of clinical and psychological variables, a series of multiple regression analyses were designed and made. The study sample consisted of 76 women with FM (49.61 ± 10.07 years). All dimensions of HRQOL were affected in FM, especially Physical Functioning, Physical Role Functioning and General Health. The mean FIQ total score was 68.59 ± 17.54, and 40 patients (53%) presented scores ≥70. Pain intensity, assessed by a 10-cm visual analogue scale (VAS), was a significant predictor of HRQOL in expressing association with FIQ and all dimensions of SF-36, except Emotional Role Functioning. Anxiety (Hospital Anxiety and Depression Scale (HADS)) was a significant predictor of the Mental Component and General Health (SF-36). Depression (HADS) was related with Vitality, Mental Health and FIQ. Emotion-focused coping was related with General Health and Emotional Role Functioning, and social support (Satisfaction with Social Support Scale (ESSS)) was related with the Social Functioning. These clinical and psychological variables explained an acceptable proportion of variability (R (2)), ranging from 31.3% on Emotional Role Functioning to 70.6% on FIQ, except for Physical Role Functioning (R (2) = 6.1). FM has a negative impact on both general and specific dimensions of HRQOL, especially the physical dimensions. Pain intensity, anxiety and depression symptoms and the emotion-focused coping are the most relevant explanatory variables of the impact of FM on HRQOL.


Stop state classification in intracortical brain-machine-interface.
Invasive brain-machine-interface (BMI) has the prospect to empower tetraplegic patients with independent mobility through the use of brain-controlled wheelchairs. For the practical and long-term use of such control systems, the system has to distinguish between stop and movement states and has to be robust to overcome non-stationarity in the brain signals. In this work, we investigates the non-stationarity of the stop state on neural data collected from a macaque trained to control a robotic platform to stop and move in left, right, forward directions We then propose a hybrid approach that employs both random forest and linear discriminant analysis (LDA). Using this approach, we performed offline decoding on 8 days of data collected over the course of three months during joystick control of the robotic platform. We compared the results of using the proposed approach with the use of LDA alone to perform direct classifications of stop, left, right and forward. The results showed an average performance increment of 22.7% using the proposed hybrid approach. The results yielded significant improvements during sessions where LDA showed a heavy bias towards the stop state. This suggests that the proposed hybrid approach addresses the non-stationarity in the stop state and subsequently facilitates a more accurate decoding of the movement states.


The value of reanalysis and replication: introduction to special section.
In their 2007 article in this journal, Duncan et al. examined 6 longitudinal data sets to gauge the links between 3 key elements of readiness at school entry (academic, attention, and socioemotional skills) and later achievement. Across all 6 data sets, the strongest predictors of later achievement were school-entry math, reading, and attention skills. Social skills and internalizing and externalizing behavior did not predict subsequent achievement, even among children with relatively high levels of problem behavior. Patterns of association were similar for boys and girls and were not moderated by socioeconomic status. The 5 articles in this section reconsider the original findings and reanalyze the data involved. Overall, the thrust of these articles confirms the original article. The articles in this section, however, do offer some new insights. In general, the articles find somewhat more support for socioemotional factors, especially for prosocial skills, but the relationships involved are very small. Perhaps the most striking new finding is the added emphasis on fine motor skills, which is the focus of 2 articles. Taken together, the articles reveal the value of reanalysis and replication in developmental psychology.


Characteristics and clinical assessment of unexplained sudden cardiac arrest in the real-world setting: focus on idiopathic ventricular fibrillation.
Recent studies have shown that in more than half of apparently unexplained sudden cardiac arrests (SCA), a specific aetiology can be unmasked by a careful evaluation. The characteristics and the extent to which such cases undergo a systematic thorough investigation in real-life practice are unknown. Data were analysed from an ongoing study, collecting all cases of out-of-hospital cardiac arrest in Paris area. Investigations performed during the index hospitalization or planned after discharge were gathered to evaluate the completeness of assessment of unexplained SCA. Between 2011 and 2016, among the 18 622 out-of-hospital cardiac arrests, 717 survivors (at hospital discharge) fulfilled the definition of cardiac SCA. Of those, 88 (12.3%) remained unexplained after electrocardiogram, echocardiography, and coronary angiography. Cardiac magnetic resonance imaging yielded the diagnosis in 25 (3.5%) cases, other investigations accounted for 14 (2.4%) additional diagnoses, and 49 (6.8%) patients were labelled as idiopathic ventricular fibrillation (IVF) (48.7 ± 15 years, 69.4% male). Among those labelled IVF, only 8 (16.3%) cases benefited from a complete workup (including pharmacological testing). Younger patients [odds ratio (OR) 6.00, 95% confidence interval (CI) 1.80-22.26] and those admitted to university centres (OR 3.60, 95% CI 1.12-12.45) were more thoroughly investigated. Genetic testing and family screening were initiated in only 9 (18.4%) and 12 (24.5%) cases, respectively. Our findings suggest that complete investigations are carried out in a very low proportion of unexplained SCA. Standardized, systematic approaches need to be implemented to ensure that opportunities for specific therapies and preventive strategies (including relatives) are not missed.


A case of anaplastic meningioma in a dog.
A tumor sized in 2.0x2.0x2.5 cm developed in the cerebellum of a female Beagle was pathologically investigated. Histopathologically, the tumor grew by compression and partially by infiltration into the adjacent cerebellar parenchyma. There were a large number of necrotic lesions and proliferation of collagen fibers. The tumor cells had oval nucleus showing cellular atypia and a high mitotic index. The tumor cells were reacted with vimentin antibody on immunostain. Electron microscopic examination revealed the tumor cells interdigitated with cytoplasmic processus where the desmosomes developed on cell junction. This tumor was diagnosed as anaplastic meningioma, which is rarely observed in dogs.


[Four boys with multiple floppy valves involving all cardiac valves and hyperextensive joints].
We experienced four boys (two siblings) whose cardiac valves were all prolapsed, which have never been reported as a recognized disease. All had hyperextensive joints without any other stigmata of Marfan or Ehlers-Danlos syndrome. The severity and progression of regurgitation of each valve differed by a case, though they had similar echocardiographic findings consistent with the diagnosis of multiple floppy valves. Three of the four patients had severe aortic regurgitation, and two received aortic valve replacement. Their excised valves revealed myxomatous degeneration. The tricuspid valves were more thickened and redundant than the mitral valves. Although three patients had moderate tricuspid regurgitation, none of them had clinically important mitral regurgitation. We recommend aortic and/or mitral valve replacement, whenever the regurgitation exacerbates left ventricular dilatation. Aortic regurgitation deteriorated rapidly in one case due to valve rupture. In this case, moderate tricuspid regurgitation was relieved after aortic valve replacement. Skin fibroblast did not show any abnormalities in collagen biosynthesis.


Is there a diminishing role for surgery for Merkel cell carcinoma of the skin? a review of current management.
Merkel cell carcinoma is a highly malignant skin tumour that must be managed in a multidisciplinary forum. Excisional biopsy of the primary is recommended and this should be followed by postoperative radiotherapy to the primary site, in-transit areas and the draining lymph nodes. The tumour is quite radiosensitive and radiation doses of the order of 50 Gy offer high levels of local control. Resection margins of 3 cm are not required provided postoperative radiotherapy is used. In the event of inoperable disease, patient refusal of surgery or a frail patient, radiotherapy should be used as the sole treatment modality, with high likelihood of achieving local control. Patients with involved nodes have a higher risk of distant disease. Traditionally, involved nodes have been managed with resection but, currently, there are protocols exploring the use of synchronous chemoradiotherapy as definitive treatment. Although adjuvant chemotherapy has been used in this setting to reduce the risk of distant seeding, the benefits at this stage have not been confirmed conclusively. The presence of distant disease carries a grave outlook and responses to chemotherapy occur frequently, but are usually shortlived.


Galectin-8 in the onset of the immune response and inflammation.
Galectins (Gals), a family of mammalian lectins, have emerged as key regulators of the immune response, being implicated in several physiologic and pathologic conditions. Lately, there is increasing data regarding the participation of Galectin-8 (Gal-8) in both the adaptive and innate immune responses, as well as its high expression in inflammatory disorders. Here, we focus on the pro- and anti-inflammatory properties of Gal-8 and discuss the potential use of this lectin in order to shape the immune response, according to the context.


Purification and characterization of the raffinose oligosaccharide chain elongation enzyme, galactan : galactan galactosyltransferase (GGT), from Ajuga reptans leaves.
Galactan: galactan galactosyltransferase (GGT), an enzyme involved in the biosynthesis of the long-chain raffinose family of oligosaccharides (RFOs) in Ajuga reptans, catalyses the transfer of an alpha-galactosyl residue from one molecule of RFO to another one resulting in the next higher RFO oligomer. This novel galactinol (alpha-galactosyl-myo-inositol)-independent alpha-galactosyltransferase is responsible for the accumulation of long-chain RFOs in vivo. Warm treatment (20 degrees C) of excised leaves resulted in a 34-fold increase of RFO concentration and a 200-fold increase of GGT activity after 28 days. Cold treatment (10 degrees C/3 degrees C day/night) resulted in a 26- and 130-fold increase, respectively. These data support the role of GGT as a key enzyme in the synthesis and accumulation of long-chain RFOs. GGT was purified from leaves in a 4-step procedure which involved fractionated precipitation with ammonium sulphate as well as lectin affinity, anion exchange, and size-exclusion chromatography and resulted in a 200-fold purification. Purified GGT had an isoelectric point of 4.7, a pH optimum around 5, and its transferase reaction displayed saturable concentration dependence for both raffinose (Km = 42 mM) and stachyose (Km = 58 mM). GGT is a glycoprotein with a 10% glycan portion. The native molecular mass was 212 kDa as determined by size-exclusion chromatography. Purified GGT showed one single active band after native PAGE or IEF separation, respectively, which separated into three bands on SDS-PAGE at 48 kDa, 66 kDa, and 60 kDa. The amino acid sequence of four tryptic peptides obtained from the major 48-kDa band showed a high homology to plant alpha-galactosidase (EC 184.108.40.206) sequences. GGT differed, however, in its substrate specificity from alpha-galactosidases; it neither hydrolysed nor transferred alpha-galactosyl-groups from melibiose, galactinol, UDP-galactose, manninotriose, and manninotetrose. Galactinol, sucrose, and galactose inhibited the GGT reaction considerably at 10-50 mM.


Validation of the Young Schema Questionnaire-Short Form in a Flemish Community Sample.
The Young Schema Questionnaire (YSQ, Young, 1994) was developed to assess Early Maladaptive Schemas (EMS), which account for the dysfunctional beliefs in individuals with personality disorders or maladaptive personality traits. This study aims to investigate the factor structure, the reliability and the validity of the original YSQ - Short Form (Young & Brown, 1998; YSQ-SF, 15 EMS) as well as an extension including 16 EMS, based on the 16 factor structure of the YSQL2 (Young & Brown, 1998) in a community sample. The sample consisted of 672 participants (51% females; M age-total = 44.34; SD age-total = 16.24). Results show evidence for both the 15 and 16 factor solution of the YSQ-SF with good internal consistency coefficients for the different scales. Significant gender differences were observed for Self-Sacrifice (females higher) and Entitlement (men higher), along with different patterns of correlations between age and Insufficient Self-Control (r = -.19), Enmeshment (r = -0.16) and Self-Sacrifice (r = .13). Furthermore, Big Five personality traits were significantly associated with several schema scales. In sum, we can conclude that both the YSQ-SF15 and 16 are valid instruments to assess EMS among a Flemish community sample. However, given the unique additive value of the 16th EMS (Social Undesirability) in predicting lower scores on Extraversion and Openness, the use of the YSQ-SF16 could be favored.


Imaging Characteristic of 11 Lesions of Odontogenic Keratocyst in the Indian Subpopulation: A Cone-Beam Computed Tomography Experience.
The clinical feature and radiographic appearance of orthokeratinized odontogenic keratocyst (OKC) are not characteristic, which may lead to the misdiagnosis. The radiographic appearance of OKC may range from a small unilocular radiolucency to a large multilocular radiolucency, resembling other odontogenic cysts and tumors. The aim was to illustrate the characteristic feature of OKC presented on the digital panoramic radiograph and cone-beam computed tomography (CBCT), which may provide great value for the differential diagnosis and the treatment planning and also to compare the various radiographic features of OKC in CBCT and digital panoramic radiograph. Digital panoramic and CBCT records of seven cases, with 11 lesions of OKC were analyzed retrospectively from the patients' database from our institute (2014 to 2016), which was histopathologically diagnosed as OKC. The mean age of the patients was 24.1 years, and the female-to-male ratio was 3: 4. Six of 11 lesions were localized within the mandible, and five lesions were in the maxilla. The presurgical assessment with radiological information is extremely important for treatment planning, and CBCT provides us with an accurate and faster three-dimensional representation of a lesion at a lower dose and cost, but the role of panoramic radiograph cannot be refuted.


Recent advancements in multimodality treatment of gliomas.
Gliomas account for the vast majority of malignant adult brain tumors. Even though tremendous effort has been made to optimize treatment of patients with high-grade glioma, the prognosis remains poor, especially for patients with glioblastoma. The dismal prognosis conferred by these tumors is in part caused by the tendency to diffusely infiltrate into neighboring brain tissue, but also by the inherent resistance of these tumors to both chemotherapy and radiation. This article reviews the recent advancements in multimodality treatment of patients with gliomas, both in the primary and recurrent setting, with an emphasis on the emerging targeted therapies. Moreover, the external beam radiotherapy options, including intensity modulated radiotherapy and particle (proton and carbon ion) radiotherapy are reviewed.


Paroxetine: a new serotonin reuptake inhibitor for the treatment of depression.
The introduction of the selective serotonin reuptake inhibitors (SSRIs) over the past several years has made a major impact on the treatment of depression and other neuropsychiatric disorders. Agents in this heterogeneous group of compounds are generally better tolerated and less toxic than the tricyclic antidepressants (TCAs), which they have in many respects superseded. This review summarizes available data on paroxetine, the newest SSRI to receive approval for the treatment of depression.


A singular case of prophage complementation in mutational activation of recET orthologs in Salmonella enterica serovar Typhimurium.
A class of mutations that suppress the recombination defects of recB mutants in Salmonella enterica serovar Typhimurium strain LT2 activates the normally silent recET module of the Gifsy-1 prophage. Allele sbcE21 is a 794-bp deletion within the immunity region of the prophage. Concomitant with activating recET, sbcE21 stimulates Gifsy-1 excision, resulting in unstable suppression. Early studies found both recB suppression and its instability to depend on the presence of the related Gifsy-2 prophage elsewhere in the chromosome. In cells lacking Gifsy-2, the sbcE21 allele became stable but no longer corrected recB defects. Here, we show that a single Gifsy-2 gene is required for Gifsy-1 recET activation in the sbcE21 background. This gene encodes GtgR, the Gifsy-2 repressor. Significantly, the sbcE21 deletion has one end point within the corresponding gene in the Gifsy-1 genome, gogR, which in strain LT2 is a perfect duplicate of gtgR. The deletion truncates gogR and places the Gifsy-1 left operon, including the recET and xis genes, under the control of the gogR promoter. The ability of GtgR to trans-activate this promoter therefore implies that GtgR and GogR normally activate the transcription of their own genes. Consistent with the symmetry of the system, a similar deletion in Gifsy-2 results in a Gifsy-1-dependent sbc phenotype (sbcF24). Two additional Gifsy-1 deletions (sbcE23 and sbcE25) were characterized, as well. The latter causes all but the last codon of the gogR gene to fuse, in frame, to the second half of recE. The resulting hybrid protein appears to function as both a transcriptional regulator and a recombination enzyme.


Development of a diagnostic one-tube RT-PCR for the detection of Rift Valley fever virus.
Diagnosis of Rift Valley fever (RVF) is based on serology and virus isolation. The disadvantages of the former include poor sensitivity, high cost, risks associated with using infectious virus as antigen, the lengthy duration of ELISA as well as cross-reactivity with other Phleboviruses. We developed, optimised and evaluated a one-tube reverse-transcription-polymerase chain reaction (RT-PCR) for the detection of Rift Valley fever virus (RVFV) in ruminants. The PCR primers for this assay were designed to anneal to a region within the M segment of the virus genome, encoding glycoproteins G1 and G2. A PCR amplicon of 363 bp was obtained. The sensitivity of the assay was determined to be 0.25 TCID50. This test should allow for the early and rapid detection of RVFV in both serum and whole blood. In addition, it could facilitate the quantification of antigen for the manufacture of current vaccines.


Characterizing the emissions of polybrominated diphenyl ethers (PBDEs) and polybrominated dibenzo-p-dioxins and dibenzofurans (PBDD/Fs) from metallurgical processes.
This study investigated the characteristics of polybrominated diphenyl ethers (PBDEs) and polybrominated dibenzo-p-dioxins and dibenzofurans (PBDD/Fs) in the stack flue gases of the metallurgical processes. An examination of the PBDEs existing in the stack flue gases of sinter plants revealed that PBDEs can form during the combustion processes through the similar formation conditions of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs). The PBDD/F and PBDE emission rates of the metallurgical facilities were 0.446-3.19 microg TEQ/h and 4470-27000 microg/h, correspondingly. Both emission rates could reach several orders higher than those of the reported sources, revealing that the metallurgical facilities are not only important PCDD/F but also significant PBDD/F and PBDE emission sources to the environment. BDE-209 is the most abundant PBDE congener in the emissions of metallurgical facilities and is found to be dominant in the atmosphere and soils. However, few studies have considered metallurgical facilities as potential PBDE contributors to the environment. Because PBDEs could form or not be completely destroyed in the feeding materials in the combustion system, PBDE contributions from combustion emission sources to the atmosphere should not be ignored and need further investigation.


The treatment of Gilles de la Tourette syndrome by limbic leucotomy.
A patient with Gilles de la Tourette syndrome and severe self-injurious compulsions who had failed to respond to drug treatment and behavioural therapy obtained a complete and sustained resolution of his destructive behaviour and improvement in his tics following bilateral limbic leucotomy.


[Regional anaesthesia in children--caudal anaesthesia and trunk blocks].
In children, elective surgery is often performed in the trunk region. Regional anaesthetic techniques allow good analgesia with reduced opioid consumption, and enhance rapid discharge of the small patients. This review focuses on indication, anatomic structures, puncture techniques and potential complications of caudal anaesthesia, transversus abdominis plane block, ilioinguinal/iliohypogastric nerve block and rectus sheath block.


Diagnosis and Treatment of Bone Metastases in Breast Cancer: Radiotherapy, Local Approach and Systemic Therapy in a Guide for Clinicians.
The standard care for metastatic breast cancer (MBC) is systemic therapies with imbrication of focal treatment for symptoms. Recently, thanks to implementation of radiological and metabolic exams and development of new target therapies, oligometastatic and oligoprogressive settings are even more common-paving the way to a paradigm change of focal treatments role. In fact, according to immunophenotype, radiotherapy can be considered with radical intent in these settings of patients. The aim of this literature review is to analyze available clinical data on prognosis of bone metastases from breast cancer and benefits of available treatments for developing a practical guide for clinicians.


The Rop GTPase switch controls multiple developmental processes in Arabidopsis.
G proteins are universal molecular switches in eukaryotic signal transduction. The Arabidopsis genome sequence reveals no RAS small GTPase and only one or a few heterotrimeric G proteins, two predominant classes of signaling G proteins found in animals. In contrast, Arabidopsis possesses a unique family of 11 Rop GTPases that belong to the Rho family of small GTPases. Previous studies indicate that Rop controls actin-dependent pollen tube growth and H(2)O(2)-dependent defense responses. In this study, we tested the hypothesis that the Rop GTPase acts as a versatile molecular switch in signaling to multiple developmental processes in Arabidopsis. Immunolocalization using a general antibody against the Rop family proteins revealed a ubiquitous distribution of Rop proteins in all vegetative and reproductive tissues and cells in Arabidopsis. The cauliflower mosaic virus 35S promoter-directed expression of constitutively active GTP-bound rop2 (CA-rop2) and dominant negative GDP-bound rop2 (DN-rop2) mutant genes impacted many aspects of plant growth and development, including embryo development, seed dormancy, seedling development, lateral root initiation, morphogenesis of lateral organs in the shoot, shoot apical dominance and growth, phyllotaxis, and lateral organ orientation. The rop2 transgenic plants also displayed altered responses to the exogenous application of several hormones, such as abscisic acid-mediated seed dormancy, auxin-dependent lateral shoot initiation, and brassinolide-mediated hypocotyl elongation. CA-rop2 and DN-rop2 expression had opposite effects on most of the affected processes, supporting a direct signaling role for Rop in regulating these processes. Based on these observations and previous results, we propose that Rop2 and other members of the Rop family participate in multiple distinct signaling pathways that control plant growth, development, and responses to the environment.


Fish consumption and advisory awareness among older Wisconsin fishermen.
The provision of fish consumption advice issued by the Wisconsin Department of Health Services (DHS) and Department of Natural Resources (DNR) has evolved over the past 40 years. In 2010, DHS received a US Environmental Protection Agency Great Lakes Restoration Initiative (GLRI) grant to evaluate existing advisory approaches, identify gaps, and adapt current communication approaches. Previous research conducted by DHS found that older, male anglers eat more sport fish and have higher body burdens of persistent contaminants found in fish than other groups. As part of the GLRI, Wisconsin DHS and DNR aimed to engage this subpopulation and improve communication by using an Internet-based survey to collect information about fishing habits, consumption, and advisory awareness. At the end of the survey, participants were provided with answers to advisory questions and links to relevant online information. From fall 2011 through spring 2012, 827 men aged 50 and older completed this survey. Nearly all fishermen were aware of the existence of consumption advisories. Although awareness was high, penetration of traditional outreach materials was low with fewer than 35% having seen any of the pamphlets featured in the survey. Knowledge of the advisories was significantly higher among residents of counties along Lakes Michigan and Superior and among more frequent sport fish consumers. Men who were aware of these advisories were significantly more likely to have modified their consumption behavior. Wisconsin's experience suggests general awareness among older male anglers. Participation in the online survey and responses to sources of advisory information supports the need to expand the current outreach program to reach and inform the fish-consuming public.