Objective evidence for the use of polylactic acid implants in HIV-associated facial lipoatrophy using three-dimensional surface laser scanning and psychological assessment.
The advent of highly active antiretroviral therapy (HAART) has dramatically improved the life expectancy of people infected with human immunodeficiency virus (HIV). Although patients often have excellent disease control with these combinations of antiretrovirals, they are at risk for the multiple toxicities associated with these drugs. Facial lipoatrophy is a particularly distressing complication of some HAART regimes. This disfigurement can lead to significant psychosocial stress, resulting in decreased treatment compliance. Polylactic acid (PLA) facial implants provide a potential method of restoring a normal appearance. One hundred consecutive patients had a course of PLA facial implants. All patients were assessed clinically and had photographs, facial surface laser scans and completed psychological questionnaires throughout the course of treatment. After a mean of 4.85 treatments per patient, there were improvements in all measures. The mean clinical scores improved from a moderate-severe grade to none-mild grade after treatment. Three-dimensional (3D) laser surface scans showed a volume increase of 2.81 cc over the treated area of the cheek. There were significant improvements in all of the psychological measures. This study shows clear objective evidence of the psychological and physical benefit of PLA implants in HIV-associated facial lipodystrophy.


Pachydermoperiostosis with bilateral ptosis and its associated systemic comorbidities: a rare case report.
Pachydermoperiostosis is a rare genetic disease known as primary or idiopathic hypertrophic osteoarthropathy (HOA)/Touraine-Solente-Gole syndrome. It is an autosomal dominant or recessive disorder comprising digital clubbing, periostosis, hyperhidrosis, and pachydermia (thickening of facial skin). Ocular manifestations are uncommon; however, blepharoptosis may occur. This case presented with severe bilateral ptosis due to the disease progression. A large 20 mm upper lid resection with levator advancement was performed to improve his ability to see. This is the first reported case of pachydermoperiostosis (PDP) in Jamaica. We present a rare case of pachydermoperiostosis with severe blepharoptosis, who attained a good result with surgical intervention.


Piggy-back pacing: implantation of pacemaker and defibrillator on top of each other.
Following the publication of several landmark trials, there has been a significant increase in the cardiac device implantation. Within this population there are a number of patients who have pre-existing cardiac devices that have been placed for a number of different conditions. While the usual approach is to remove the existing unit and replace it with a new device with the removal or capping of existing lead systems, this practice often sacrifices an existing unit that still possesses good battery longevity. We explored the possibility of separating the pacing and defibrillating functions by implanting a new device on the top of the old device in a 'piggy-back fashion'. We report a series of four cases (with various indications) with differing combinations of devices. The procedure was performed safely in every one of them, and no device-device interaction was noted. Combining the new with existing units in a 'piggy-back' manner may be a safe and cost-effective technique in the selected cases.


Activity and Cell-Death Pathway in Leishmania infantum Induced by Sugiol: Vectorization Using Yeast Cell Wall Particles Obtained From Saccharomyces cerevisiae.
Visceral leishmaniasis, caused by Leishmania infantum, is a neglected tropical disease, to which efforts in the innovation of effective and affordable treatments remain limited, despite the rising incidence in several regions of the world. In this work, the antileishmanial effects of sugiol were investigated in vitro. This compound was isolated from the bark of Cupressus lusitanica and showed promising activity against L. infantum. In spite of the positive results, it is known that the compound is a poorly water-soluble diterpene molecule, which hinders further investigation, especially in preclinical animal studies. Thus, in an alternative delivery method, sugiol was entrapped in glucan-rich particles obtained from Saccharomyces cerevisiae yeast cell walls (YCWPs). To evaluate the activity of sugiol, the experiments were divided into two parts: (i) the in vitro investigation of antileishmanial activity of free sugiol against L. infantum promastigotes after 24, 48, and 72 h of treatment and (ii) the evaluation of antileishmanial activity of sugiol entrapped in glucan-rich particles against intracellular L. infantum amastigotes. Free sugiol induced the cell-death process in promastigotes, which was triggered by enhancing cytosolic calcium level and promoting the autophagy up to the first 24 h. Over time, the presence of autophagic vacuoles became rarer, especially after treatment with lower concentrations of sugiol, but other cellular events intensified, like ROS production, cell shrinkage, and phosphatidylserine exposure. Hyperpolarization of mitochondrial membrane potential was found at 72 h, induced by the mitochondria calcium uptake, causing an increase in ROS production and lipid peroxidation as a consequence. These events resulted in the cell death of promastigotes by secondary necrosis. Sugiol entrapped in glucan-rich particles was specifically recognized by dectin-1 receptor on the plasma membrane of macrophages, the main host cell of Leishmania spp. Electron micrographs revealed particles containing sugiol within the infected macrophages and these particles were active against the intracellular L. infantum amastigotes without affecting the host cell. Therefore, the YCWPs act like a Trojan horse to successfully deliver sugiol into the macrophage, presenting an interesting strategy to deliver water-insoluble drugs to parasitized cells.


Human-Animal Chimeras and Hybrids: An Ethical Paradox behind Moral Confusion?
The prospect of creating and using human-animal chimeras and hybrids (HACHs) that are significantly human-like in their composition, phenotype, cognition, or behavior meets with divergent moral judgments: on the one side, it is claimed that such beings might be candidates for human-analogous rights to protection and care; on the other side, it is supposed that their existence might disturb fundamental natural and social orders. This paper tries to show that both positions are paradoxically intertwined: they rely on two kinds of species arguments, "individual species arguments" and "group species arguments," which formulate opposing demands but are conceptually interdependent. As a consequence, the existence of HACHs may challenge exactly those normative standards on which the protection of HACHs may eventually be based. This ethical paradox could constitute the ultimate source of the "moral confusion" that some authors have suspected HACHs to provoke.


Aceruloplasminaemia with progressive atrophy without brain iron overload: treatment with oral chelation.
Hereditary aceruloplasminaemia is a disorder of iron metabolism that is characterised by iron accumulation in the brain and other visceral organs. In previously reported cases, individuals with the disorder were noted to have evidence of iron accumulation in the brain. Oral chelating agents have not been used in neurological diseases of iron metabolism. A 54-year-old woman who presented with ataxia, lower extremity spasticity and chorea was evaluated for evidence of the source of neurological dysfunction. Blood studies revealed no detectable ceruloplasmin. Marked iron overload was defined by a liver biopsy, which showed a variegated pattern consistent with a primary cause of iron overload. Review of MRI scans showed progressive brain atrophy without visible iron accumulation occurring over a 5-year period. The history suggested that neurodegeneration was coincident with aggressive oral iron replacement. Oral chelation improved many symptoms. Our findings in this patient suggest that disorders of iron transport such as aceruloplasminaemia can be a cause of neurological symptoms such as chorea and cognitive decline, as well as progressive neurodegeneration in the absence of visible iron on MRI scans. We found that oral iron chelation was effective at improving symptoms.


[No increase in the prevalence of vertebral fractures among postmenopausal women over a 10-year period].
We examined whether the prevalence of vertebral fracture in otherwise healthy, 70-year-old Danish women had increased over a period of ten years. The population-based, epidemiological study included two age-matched, representative samples of postmenopausal women. Group 1 (1979) consisted of 173 healthy women without secondary causes of osteoporosis, Group 2 (1989) of 387 women. X-rays of the thoraco-lumbar spine were assessed for vertebral fracture by five radiological methods. There was no significant difference between the two groups in the prevalence of vertebral fracture and the 95% confidence intervals overlapped completely in all methods. The prevalence rates varied by method from 35% to 80% but the distribution of fracture types was similar in the two groups. We conclude that the prevalence of vertebral fractures due to postmenopausal osteoporosis has not increased since 1979 in suburban Copenhagen, and that comparison of prevalences requires the same method of radiological assessment.


1-Deamino-8-D-arginine vasopressin as a therapy for the bleeding diathesis of renal failure.
The treatment of the bleeding diathesis of renal failure remains unsatisfactory. 1-Deamino-8-D-arginine vasopressin (DDAVP) has recently been shown to shorten the prolonged bleeding time of renal failure and may as a result diminish the risk of clinical hemorrhage. We describe 2 cases where DDAVP was used successfully in the management of hemorrhage in the setting of renal insufficiency.


Adiposity contributes to differences in left ventricular structure and diastolic function with age in healthy men.
We sought to examine the influence of adiposity in age-associated changes in the left ventricle (LV) in a cohort of 113 healthy men, aged 20-79 yr, by measuring LV structure and diastolic function (echocardiography), whole body composition, and regional adiposity (dual energy x-ray absorptiometry). Aging was associated with increased levels of adiposity, greater wall thickness to chamber radius ratio, LV concentric remodeling, and reduced LV diastolic function (all P < 0.05). Bivariate correlation analysis showed that mean LV wall thickness, a concentric LV morphology, and diastolic function were related to adiposity (r = -0.63 to 0.51; all P < 0.05). The relation between age and both mean LV wall thickness and concentric remodeling was reduced after controlling for percentage total body fat (by 38% and 54%, respectively), percentage abdominal fat (by 42% and 62%), and the abdominal/thigh fat ratio (by 35% and 46%). The diastolic function-age relation was reduced after controlling for percentage total body fat (by 35%), percentage abdominal fat (by 39%), and the abdominal/thigh fat ratio (by 29%). There were no apparent differences in the contribution of percentage total body fat, percentage abdominal fat, or abdominal/thigh fat to the association between age and LV structure/diastolic function. We conclude that increasing adiposity contributes to the LV remodeling/reduced diastolic function that occurs with aging in healthy men.


Nitrososynthase-triggered oxidative carbon-carbon bond cleavage in baumycin biosynthesis.
Baumycins are coproduced with the clinically important anticancer secondary metabolites daunorubicin and doxorubicin, which are glycosylated anthracyclines isolated from Streptomyces peucetius. The distinguishing feature of baumycins is the presence of an unusual acetal moiety appended to daunosamine, which is hydrolyzed during acidic extraction of daunorubicin from fermentation broth. The structure of the baumycin acetal suggests that it is likely derived from an unknown C3″-methyl deoxysugar cleaved between the C3″ and C4″ positions. This is supported by analysis of the baumycin/daunorubicin biosynthetic gene cluster (dox), which also encodes putative proteins consistent with production of an anthracycline dissacharide containing a branched sugar. Notably, the dnmZ gene in the dox gene cluster possesses high translated sequence similarity to nitrososynthases, which are flavin-dependent amine monooxygenases involved in the four-electron oxidation of amino sugars to nitroso sugars. Herein we demonstrate that DnmZ is an amino sugar nitrososynthase that initiates the conversion of thymidine-5'-diphosphate-l-epi-vancosamine to a ring-opened product via a previously uncharacterized retro oxime-aldol reaction.


Specific immunotherapy with Dermatophagoides pteronyssinus and D. farinae results in decreased bronchial hyperreactivity.
To evaluate the tolerability and efficacy of specific immunotherapy with mite extracts, we performed a double-blind, placebo-controlled immunotherapy study in 30 patients with proven allergy to mite allergens. The specific immunotherapy with standardized extracts of Dermatophagoides pteronyssinus and D. farinae by a clustered rush protocol was well tolerated. After 1 year of treatment, the actively treated group showed a significant improvement compared to their starting value as well as to the placebo-treated patients with regard to skin prick test, conjunctival provocation test, and subjective rhinitis score. The subjective asthma score and bronchial hyperreactivity, measured by the methacholine provocation test, was improved in comparison to the starting value, but not to the placebo group, after 12 months. However, a further, open comparison of the placebo- and verum-treated groups at 18 months revealed a significant reduction. The drug intake was not increased in the verum-treated group. Exposure to mite levels was constant throughout this time period, as revealed by antigen measurement. We conclude that specific immunotherapy in perennial, mite-allergen-induced asthma may reduce not only immediate, IgE-mediated symptoms but, after a rather long time period of 12-18 months, also the inflammatory component of bronchial asthma, thus leading to a reduction of unspecific hyperreactivity.


Application of a three dimensional polyethyleneimine functionalized graphene oxide aerogel as an adsorbent for the determination of phytohormones in ginseng.
Aerogels have attracted considerable attention in sample pretreatment for their outstanding properties, such as the unique porous structure, large surface area and abundant modifiable active sites. The present research reports a three-dimensional interconnected porous network aerogel (PEI-AGO) manufactured based on graphene oxide (GO), polyethyleneimine (PEI) and agar as basic materials through a vacuum freeze-drying treatment. The PEI-AGO aerogel exhibits great potential as a solid phase extraction adsorbent for the selective purification of six endogenous plant hormones in conjunction with high performance liquid chromatography-electrospray ionization tandem mass spectrometry (LC-MS). Several factors affecting the extraction efficiency were investigated. Under the optimized extraction conditions, a wide linear range of 0.5-100 ng mL-1 with a good linearity (r > 0.9934) was observed. Low limits of detection (LODs) and limits of quantification (LOQs) were obtained in the range of 0.032-0.155 ng mL-1 and 0.107-0.518 ng mL-1, respectively. Furthermore, the relative recoveries for spiked ginseng samples exhibited remarkable consistency, ranging from 90.2% to 117.6%, with a relative standard deviation (RSD) of ≤9.4% (n = 3). In summary, PEI-AGO has proven to be an effective adsorbent for the pretreatment and enrichment of phytohormones which can be used for the determination of trace endogenous acidic plant hormones in ginseng leaves.


A theoretical framework for gene induction and experimental comparisons.
Ligand-mediated gene induction by steroid receptors is a multistep process characterized by a dose-response curve for gene product that follows a first-order Hill equation. This behavior has classically been explained by steroid binding to receptor being the rate-limiting step. However, this predicts a constant potency of gene induction (EC(50)) for a given receptor-steroid complex, which is challenged by the findings that various cofactors/reagents can alter this parameter in a gene-specific manner. These properties put strong constraints on the mechanisms of gene induction and raise two questions: How can a first-order Hill dose-response curve (FHDC) arise from a multistep reaction sequence, and how do cofactors modify potency? Here we introduce a theoretical framework in which a sequence of steps yields an FHDC for the final product as a function of the initial agonist concentration. An exact determination of all constants is not required to describe the final FHDC. The theory predicts mechanisms for cofactor/reagent effects on gene-induction potency and maximal activity and it assigns a relative order to cofactors in the sequence of steps. The theory is supported by several observations from glucocorticoid receptor-mediated gene induction. It identifies the mechanism and matches the measured dose-response curves for different concentrations of the combination of cofactor Ubc9 and receptor. It also predicts that an FHDC cannot involve the DNA binding of preformed receptor dimers, which is validated experimentally. The theory is general and can be applied to any biochemical reaction that shows an FHDC.


[Hyper-IgE syndrome--two case reports of unusual complications].
The hyper-IgE syndrome (HIS) is a complex immunologic disease, caused by an unknown basic defect. We report on two cases showing complications, which have not been described so far. Case 1: A 15-year-old boy suffering from HIS developed a liver tumour with severe eosinophilic infiltration and degranulation. The transformation process of the liver histologically resembled focal nodular hyperplasia. Therapy with cyclosporine A did not lead to clinical benefit. Now, a therapeutic attempt with interferon gamma is made. Case 2: In a 17-year-old female HIS patient, multiple papillomas and ulcers of the mucous membrane, caused by infection with human papilloma virus, emerged in the ENT region. Under treatment with interferon alpha, papillomatosis could be restrained. As therapy of the hyper-IgE syndrome only symptomatic treatment has been recommended so far. Future therapies should strive for systemic immunomodulation by application of cytokines or soluble cytokine receptors like interferons or sIL-4R.


[Fatty acid composition of variant Staphylococcus aureus 209 P resistant to antibiotic AL-87].
The antibiotic AL-87 resistant variant of S. aureus 209P was grown on the antibiotic-free medium. The study on its fatty acid composition showed that it was analogous to the fatty acid composition of the initial sensitive strain with the predominance of branched fatty acids. However, when the resistant variant was grown on the antibiotic-containing medium, it was characterized by a markedly changed fatty acid composition with the predominance of the straight chain saturated and unsaturated fatty acids, mainly hexadecanoic and octadecenic acids. The fatty acid composition of the resistant variant grown in the presence of the antibiotic was close to that of a wide range of gram-positive and gram-negative microogranisms.


Complete Chloroplast Genome Sequence of Coptis chinensis Franch. and Its Evolutionary History.
The Coptis chinensis Franch. is an important medicinal plant from the Ranunculales. We used next generation sequencing technology to determine the complete chloroplast genome of C. chinensis. This genome is 155,484 bp long with 38.17% GC content. Two 26,758 bp long inverted repeats separated the genome into a typical quadripartite structure. The C. chinensis chloroplast genome consists of 128 gene loci, including eight rRNA gene loci, 28 tRNA gene loci, and 92 protein-coding gene loci. Most of the SSRs in C. chinensis are poly-A/T. The numbers of mononucleotide SSRs in C. chinensis and other Ranunculaceae species are fewer than those in Berberidaceae species, while the number of dinucleotide SSRs is greater than that in the Berberidaceae. C. chinensis diverged from other Ranunculaceae species an estimated 81 million years ago (Mya). The divergence between Ranunculaceae and Berberidaceae was ~111 Mya, while the Ranunculales and Magnoliaceae shared a common ancestor during the Jurassic, ~153 Mya. Position 104 of the C. chinensis ndhG protein was identified as a positively selected site, indicating possible selection for the photosystem-chlororespiration system in C. chinensis. In summary, the complete sequencing and annotation of the C. chinensis chloroplast genome will facilitate future studies on this important medicinal species.


Modelling Sex-Specific Crossover Patterning in Arabidopsis.
"Interference" is a major force governing the patterning of meiotic crossovers. A leading model describing how interference influences crossover patterning is the beam-film model, a mechanical model based on the accumulation and redistribution of crossover-promoting "stress" along the chromosome axis. We use the beam-film model in conjunction with a large Arabidopsis reciprocal backcross data set to gain "mechanistic" insights into the differences between male and female meiosis, and crossover patterning. Beam-film modeling suggests that the underlying mechanics of crossover patterning and interference are identical in the two sexes, with the large difference in recombination rates and distributions able to be entirely explained by the shorter chromosome axes in females. The modeling supports previous indications that fewer crossovers occur via the class II pathway in female meiosis and that this could be explained by reduced DNA double-strand breaks in female meiosis, paralleling the observed reduction in synaptonemal complex length between the two sexes. We also demonstrate that changes in the strength of suppression of neighboring class I crossovers can have opposite effects on "effective" interference depending on the distance between two genetic intervals.


Vibration damping platform for cavity quantum-electrodynamics experiments.
We present a mechanical platform with enhanced vibration damping properties for cavity quantum-electrodynamics experiments. It is based on a composite design that combines a soft, vibration damping core with a rigid shell maintaining optical alignment. It passively damps the vibrations generated by piezoelectric actuators controlling the mirror positions. The mechanical resonances of the platform, which lead to a length change of the cavity, are efficiently suppressed up to 100 kHz. Our platform is ultra-high vacuum compatible and can be used in most applications, in particular, where long cavities and optical access to the cavity center are required.


Liposomes as protective capsules for active silica sol-gel biocomposite synthesis.
Using liposome to shield an enzyme from hostile chemical environments during the sol-gel formation process has resulted in a novel approach to synthesizing silica sol-gel biocomposite materials. By reporting the encapsulation of horseradish peroxidase and firefly luciferase, we demonstrate that this new protocol can produce silica biocomposites that are more active than trapping the enzymes directly into hydrogels.


Host defence mechanisms against fungal infection.
Recent concepts on the role of non-specific (normal) and specific (immune) defence mechanisms against fungal infection are discussed on the basis of the evidence obtained from experimental animals. Commonly occurring systemic mycoses, i.e. candidosis (candidiasis), cryptococcosis and histoplasmosis, are discussed.


Teaching Small Bite Fascial Closure Technique: Improved Accuracy and Consistency Through Simulation.
Despite evidence that small bite closure is beneficial, it is not well documented how accurately and consistently surgeons employ this technique. We created a felt model to simulate fascial closure and educate residents regarding small bites. This study aims to gauge accuracy and consistency of bite size in fascial closure and assess if utilizing a templated model could improve technique. Two 10 cm incisions were made in different pieces of felt. Residents were instructed to suture the incisions to simulate fascial closure by running the incisions closed with 1 cm and 5 mm bites respectively. The process was repeated with templated pieces of felt marking 1 and 0.5 cm to guide bite size. Residents were timed for each closure. The travel and distance from the midline for each bite was measured and analysis performed. 14 residents participated. Paired T-test compared means and standard deviations of bite size. Taking 5 mm bites took more time. Standard deviation of travel and right sided distance from midline were significantly smaller when a template was utilized. Standard deviation of travel as well as right sided distance was also improved when instructed to take 5 mm bites. This study demonstrates that a small bite technique results more closure and that when residents are instructed to take smaller bites. The adage, "aim small, miss small," holds true in fascial closure and may be one reason why small bites improve hernia rates. This study also suggests that the use of a template improves accuracy and consistency of closure regardless of bite size intention.


Interferon as a cause of endoplasmic reticulum abnormalities within hepatocytes in newborn mice.
An ultrastructural examination of livers from newborn mice, injected with potent partially purified or highly purified mouse interferon or with lymphocytic choriomeningitis (LCM) virus, has revealed the presence of tubular aggregates associated with the granular endoplasmic reticulum in the cytoplasm of hepatocytes after either treatment. Thus the lesion was observed in A2G and Swiss mice after interferon injections. It was also seen in C3H mice after LCM infection, the liver being examined at a time when the interferonaemia in the injected mice was known to be at its peak. The aggregate resembles the tubular systems associated with the endoplasmic reticulum described in various tissues in both human and animal diseases. These observations raise the possibility that in some of the cases previously described the lesion has been interferon induced.


Pediatric forearm fractures with in situ intramedullary implants.
The purpose of this investigation is to present our institutional experience with fractures of the pediatric forearm with in situ intramedullary nails. Six patients treated at our institution for forearm fracture with in situ intramedullary implants between 2004 and 2013 were reviewed. Patient demographics, injury and radiographic characteristics, method of treatment, time to union, and complications were collected from the medical record. 485 patients with forearm fractures were treated with intramedullary implants and six patients presented with a fracture with in situ implants (1.2 %). Fractures in all six patients resulted from a second traumatic event after radiographic healing but before implant removal at a mean of 13.0 months from the initial procedure. One patient had an adequately aligned fracture and was treated with casting without reduction. The remaining five patients (83 %) returned to the operating room for treatment. Two patients underwent rod removal and placement of new intramedullary implants, and two patients were treated with rod removal and plating without attempt at closed reduction. One patient underwent closed reduction in the operating room with successful re-bending of the radial implant and replacement of the ulna implant. All patients went on to uncomplicated radiographic union at a mean 3.6 months. The incidence of fracture of pediatric forearm with in situ intramedullary implants is low. This rare complication can be treated by several different methods, including revision TENS placement, revision to plate fixation, or in situ bending of rods, with the expectation for successful uncomplicated union.


Clinical manifestations and morphological changes in one case with post-stroke Klüver-Bucy syndrome.
We present the case of a 71-year-old right-handed male, admitted to the Department of Neurology, Emergency County Hospital of Arad, Romania, on November 2015, with a rare case of Klüver-Bucy syndrome (KBS), following an ischemic stroke of the right temporal lobe, which was previously diagnosed in December 2014 and was treated accordingly. At the moment of second hospital admission, the patient was found somnolent and confused at home, with traumatic signs of biting of the tongue and urine emission. A couple days after admission, our patient became alert and presented hypersexuality, hypermetamorphosis, increased oral tendency, behavior changes including apathy with loss of anger and fear, and a very increased appetite, transient visual agnosia and right-left disorientation. In the initial phase, the patient could not recognize any members of his family, but he had a tendency to touch everything within his reach and place it into his mouth. The KBS presented in this case, following an ischemic stroke of the right temporal lobe provides distinct and intriguing insights into the possible pathophysiology of this syndrome. Often disruption of consciousness during recovery period may hide the clinical manifestation of the syndrome.


Effect of antithyroid agents 6-propyl-2-thiouracil and 1-mehtyl-2-mercaptoimidazole on human thyroid iodine peroxidase.
The mechanism of inhibition of human thyroid iodide peroxidase (TPO) by 6-propyl-2-thiouracil (PTU) and 1-methyl-2-mercaptoimidazole (MMI) used in the therapy of hyperthyroid patients was studied in vitro. The inhibition of TPO by MMI was not restored either by dialysis or by dilution, but the inhibition by PTU was restored by both treatments. PTU interacted directly with the product of TPO action (oxidized iodide) in the reaction mixture without significantly affecting TPO activity. MMI interacted directly with TPO and inhibited enzyme activity, rather than interacting with the product (oxidized iodide). The inhibition was irreversible with MMI, but reversible with PTU. The concentrations of PTU and MMI producing 50% inhibition of TPO were 2 x 10-6m and 8 x 10-7m, respectively, 2-Mercaptoimidazole inhibited TPO reversibly but 1-methylimidazole and imidazole did not. Both the methyl and mercaptoresidues in MMI moiety are thought to be essential to its irreversible inhibition of TPO. The in vivo effect of MMI and PTU on TPO activity was also studied. TPO activities in the thyroid homogenate of rats to which MMI (2 mg per rat) or PTU (10 mg per rat) had been administered intraperitoneally were determined before and after dialysis against buffer. TPO activity in the PTU treated thyroid homogenate was significantly lower than that in the control before dialysis, but the activity was restored to the control value after dialysis. On the contrary, TPO activity in the MMI treated thyroid homogenate was significantly lower than that in the control and was not affected by dialysis. These data may explain why MMI is a more potent inhibitor of iodination than PTU and may fit the clinical results observed when hyperthyroid patients are treated with these agents.


The correlation between tremor characteristics and the predicted volume of effective lesions in stereotaxic nucleus ventralis intermedius thalamotomy.
In 51 cases (6 cases with bilateral operations) with various kinds of tremor, stereotaxic ventralis intermedius (Vim) thalamotomies were performed using Leksell's apparatus and the results of operation evaluated. Several characteristics of the tremor, including clinical features and EMG, were correlated with the assumed location and volume of the coagulative lesion. In 54 of the 57 operations, the thalamic Vim nucleus was identified physiologically and a therapeutic lesion placed at a site that included the Vim neurons. In all these cases, except one in which the lesion was estimated to be too small, tremor was immediately abolished by a relatively small lesion. The estimated volume of the lesion was about 40 to 200 mm3 and the effect persisted over a long follow-up period (maximum ten years). The size of the lesion that was necessary apparently depended on several features of the tremor. A larger lesion was required in cases of movement type tremor, tremor with a low rate (less than 4 Hz), tremor of high amplitude (more than 600 microV), and tremor involving proximal muscles or with a wide distribution. Tremor following a cerebrovascular lesion and post-traumatic tremor were characterized by coarse oscillation (high amplitude and low frequency) involving proximal muscles. A relatively larger coagulative lesion was therefore necessary to relieve this type of tremor. In contrast, parkinsonian and essential tremor were usually of low amplitude and distal in distribution. For the relief of such tremor, the lesion could be very small: if aided by electrophysiological methods to identify Vim neurons, the minimal effective volume of the lesion was estimated as about 40 mm3 and restricted to the Vim nucleus. Based on these results, the importance of the Vim nucleus in tremor mechanisms is discussed.


Modified Pluronic F127 Surface for Bioconjugation and Blocking Nonspecific Adsorption of Microspheres and Biomacromolecules.
Many experiments and applications require the chemical coupling of target molecules to surfaces, during which the elimination of nonspecific interactions presents a difficult challenge. We report on a technologically accessible surface passivation and chemical conjugation method based on an NHS end-labeled F127 Pluronic block copolymer (F127-NHS). To quantify interactions between the F127-NHS surface and magnetic microspheres, we developed a simple assay: the microsphere adhesion by gravity, inversion, then counting, or "MAGIC" assay. To improve blocking of microspheres while maintaining the ability to chemically couple additional molecules, we implemented a pH-dependent two-step chemical modification process for amine microspheres. This process achieves an extremely high level of blocking nonspecific interactions (less than 2% nonspecific adhesion) for a variety of microsphere surface charges and chemical functionalities. We also demonstrate the ability to specifically tether magnetic microspheres to an F127-NHS surface, using single DNA molecules. Using the DNA microspheres, we establish the applicability of the surface for force spectroscopy (stable with an applied load >30 pN) via the massively parallel technique of centrifuge force microscopy. Finally, we demonstrate that the surface can be used in fluorescence studies with a fluorogenic peptide cleavage assay, with high levels of blocking achieved for both the fluorogenic peptide and trypsin. These results suggest applications including, but not limited to, single-molecule force spectroscopy and fluorescence, biosensors, medical implants, and anti-biofouling, which could make use of the F127-NHS surface.


Dose assessment in contrast enhanced digital mammography using simple phantoms simulating standard model breasts.
Slabs of polymethyl methacrylate (PMMA) or a combination of PMMA and polyethylene (PE) slabs are used to simulate standard model breasts for the evaluation of the average glandular dose (AGD) in digital mammography (DM) and digital breast tomosynthesis (DBT). These phantoms are optimized for the energy spectra used in DM and DBT, which normally have a lower average energy than used in contrast enhanced digital mammography (CEDM). In this study we have investigated whether these phantoms can be used for the evaluation of AGD with the high energy x-ray spectra used in CEDM. For this purpose the calculated values of the incident air kerma for dosimetry phantoms and standard model breasts were compared in a zero degree projection with the use of an anti scatter grid. It was found that the difference in incident air kerma compared to standard model breasts ranges between -10% to +4% for PMMA slabs and between 6% and 15% for PMMA-PE slabs. The estimated systematic error in the measured AGD for both sets of phantoms were considered to be sufficiently small for the evaluation of AGD in quality control procedures for CEDM. However, the systematic error can be substantial if AGD values from different phantoms are compared.


Detection of pyrethroid resistance gene in head lice in schoolchildren from Bobigny, France.
The head louse, Pediculus humanus capitis (De Geer), is an hematophagous ectoparasite that affects mainly children. Resistance to insecticides belonging to pyrethroids and other pediculicides, such as malathion, is responsible for frequently reported treatment failures. Recent studies showed that a M815I-T929I-L932F kdr-like mutation in the voltage-gated sodium channel alpha-subunit gene was associated with permethrin resistance in head lice from several countries worldwide. We searched for the presence ofpyrethroid resistance gene in head lice populations obtained in schoolchildren in an urban area of France. All the 15 primary schools of Bobigny, a city located 3 km north of Paris, were selected to participate. Of 3,493 children enrolled, 3,345 (95.8%) children were screened for head lice by using fine-toothed antilouse combs. Live head lice were detected in 112 (3.3%) of children screened. A subsample of 90 lice was processed for DNA study. The amplification of a 332-bp portion of the kdr-like gene spanning the codon 929 was performed, and polymerase chain reaction products were submitted to the restriction enzyme SspI. Twenty of these lice (22.2%) were homozygous susceptible, 33 (36.7%) were homozygous resistant, and 37 (41.1%) were heterozygotes. Globally, the frequency of the T929I mutation was 0.57. The prevalence of pediculosis in schoolchildren of Bobigny seemed relatively low in comparison with findings of other European studies. The presence of the T929I mutation associated with permethrin resistance probably reflected the frequent local use of this insecticide. Further studies are now required to evaluate the prevalence of the kdr-like mutant allele in head lice in French schools.


Breakthrough adsorption study of migratory nickel in fine-grained soil.
The present study was conducted to evaluate the breakthrough curve for nickel adsorption in fine-grained soil from a nearby ash pond site of a thermal power plant. Nickel was found to be the major polluting solute in the ash sluicing wastewater. The adsorption of nickel by vertical soil column batch test and horizontal migration test was carried out in the laboratory. Field investigation was conducted also, by installing test wells around the ash pond site. Experimental results showed a good adsorptive capacity of soil for nickel ions. The breakthrough curves showed a reasonable fitting with a one-dimensional mathematical model. The breakthrough curves yielded from field test results showed good agreement with a two-dimensional mathematical model.


Epstein-Barr virus latent membrane protein 2A suppresses the expression of HER2 via a pathway involving TWIST and YB-1 in Epstein-Barr virus-associated gastric carcinomas.
To explore HER2 expression in Epstein-Barr virus-associated gastric carcinoma (EBVaGC) and the possible mechanisms causing down-regulation of HER2 expression in EBVaGC, we first evaluated HER2 and LMP2A expression on a clinicopathological-features matched cohort including 78 EBVaGC and 216 EBV-negative gastric carcinoma (EBVnGC) cases by immunohistochemistry. Cases with high HER2 expression in EBVaGC were significantly less than in EBVnGC (5.1% versus 23.7%; p<0.001), and none of the 34 LMP2A+ EBVaGC showed high HER2 expression. Further, overexpressing LMP2A in EBV-negative SGC7901 cells significantly decreased HER2, TWIST and YB-1 mRNA by 36.1%±8.1%, 87.6%±14.0% and 83.8%±5.7%, and protein by 44%, 57% and 49%, respectively. Additionally, the nucleus/cytoplasm ratios of TWIST and YB-1 were also decreased by 85% and 80%, respectively. Silencing LMP2A by siRNA in EBV-positive SNU719 cells for 48 h significantly increased HER2, TWIST and YB-1 mRNA to 276.7%±14.6%, 1284.8%±38.2% and 332.0%±15.5% and protein to 212%, 457% and 232%, respectively. The nucleus/cytoplasm ratios of TWIST and YB-1 were up-regulated by 4.00- and 3.57-fold, respectively, following LMP2A down-regulation. Moreover, LMP2A+/HER2low EBVaGC cases presented the best overall survival compared with LMP2A-/HER2low and LMP2A-/HER2high cases (p=0.003, log-rank test). These results suggest that LMP2A may suppress the HER2 expression through the TWIST/YB-1 axis in EBVaGC.


Trends in Biotechnological Drugs for Cancer Treatment.
Biotechnology, which promoted revolutions in many fields, generates great expectations for the future, mainly in the pharmaceutical sector for the treatment of several diseases. Cancer is a leading cause of death worldwide and due to its complexity and singularity, there are a number of challenges that limit the development of new drugs for antitumor therapies, making the research for cancer treatment one of the most exploited in the medical field. The main objective of this article is to identify trends of biotechnological advances that may have application in improving cancer therapies. Information from patent applications of biotechnological drugs in the last five years was retrieved using Thomson Reuters Integrity database. Cancer is the leading therapeutic condition found in patent documents. The subject matter most cited in patent applications includes monoclonal antibodies, adoptive cell therapy, RNA interference and new vaccine peptides. The analysis of the documents has provided an overview of new biological alternatives for use in cancer treatment, showing potential avenues for years to come.


Comparison of Outcomes After Reverse Total Shoulder Arthroplasty in Patients With Proximal Humerus Fractures Versus Rotator Cuff Arthropathy.
Indications for reverse total shoulder arthroplasty (rTSA) has expanded to encompass complex proximal humerus fractures (PHFs) in recent years. The purpose of this study was to report and assess whether PHF patients treated with rTSA could achieve similar functional outcomes and short-term survivorship to patients who underwent rTSA for rotator cuff arthropathy (RTCA). All consecutive patients with a preoperative diagnosis of PHF or RTCA, 18 years or older, treated with rTSA at a single academic institution between 2018 and 2020 with a minimum 2-year follow-up were retrospectively reviewed. Primary outcomes were survivorship defined as revision surgery or implant failure analyzed using the Kaplan-Meier survival curve, and functional outcomes, which included Quick Disabilities of the Arm, Shoulder, and Hand, and range of motion (ROM) were compared at multiple follow-up time points up to 2 years. Secondary outcomes were patient demographics, comorbidities, surgical data, length of hospital stay, and discharge disposition. A total of 48 patients were included: 21 patients (44%) were diagnosed with PHF and 27 patients (56%) had RTCA. The Kaplan-Meier survival rate estimates at 3 years were 90.5% in the PHF group and 85.2% in the RTCA group. No differences in revision surgery rates between the two groups (P = 0.68) or survivorship (P = 0.63) were found. ROM was significantly lower at subsequent follow-up time points in multiple planes (P < 0.05). A greater proportion of patients in the PHF group received cement for humeral implant fixation compared with the RTCA group (48% versus 7%, P = 0.002). The mean length of hospital stay was longer in PHF patients compared with RTCA patients (2.9 ± 3.8 days versus 1.6 ± 1.8 days, P = 0.13), and a significantly lower proportion of PHF patients were discharged home (67% versus 96%, P = 0.015). The rTSA implant survivorship at 3 years for both PHF and RTCA patients show comparable results. At the 2-year follow-up, RTCA patients treated with rTSA were found to have better ROM compared with PHF patients.


Fault Diagnosis of Complex Processes Using Sparse Kernel Local Fisher Discriminant Analysis.
As an outstanding discriminant analysis technique, Fisher discriminant analysis (FDA) gained extensive attention in supervised dimensionality reduction and fault diagnosis fields. However, it typically ignores the multimodality within the measured data, which may cause infeasibility in practice. In addition, it generally incorporates all process variables without emphasizing the key faulty ones when modeling the complex process, thus leading to degraded fault classification capability and poor model interpretability. To ease the above two drawbacks of conventional FDA, this brief presents an advantageously sparse local FDA (SLFDA) model, it first preserves the within-class multimodality by introducing local weighting factors into scatter matrix. Then, the responsible faulty variables are identified automatically through the elastic net algorithm, and the current optimization problem is subsequently settled through the feasible gradient direction method. Since then, the local data structure characteristics are exploited from both the sample dimension and variable dimension so that the fault diagnosis performance and model interpretability are significantly enhanced. In addition, we naturally extend SLFDA model to nonlinear variant (i.e., sparse kernel local FDA) by the kernel trick, which is substantially more resistant to strong nonlinearity. The simulation studies on Tennessee Eastman (TE) benchmark process and real-world diesel engine working process both validate that the novel diagnosis strategy is more accurate and reliable than the existing state-of-the-art methods.


Effects of loprazolam on cognitive functions.
The effects of oral loprazolam (1, 2 mg) on vigilance, attention, immediate memory, short-term memory, learning, long-term non-consolidated and long-term consolidated memory were determined. Twelve healthy young male volunteers were given all the treatments, placebo or loprazolam, on three different occasions, in a double-blind, random latin-square sequence, crossing over every 2 weeks. Volunteers completed a battery of tests at night, 3.5 h after drug administration, and in the morning, 10 h after drug administration, to test recall of some of the material presented at night (long-term memory) and residual effects. Loprazolam did not significantly impair any of the functions tested at night. On the other hand, 2 mg loprazolam caused impairment of long-term memory, both consolidated and not. This reduction of long-term memory does not seem to be related to the impairments of vigilance, attention or learning. The 2 mg dose of loprazolam, which did not modify the mean scores and improved vigilance, attention and learning in some of the subjects, reduced long-term memory. Therefore, although caution in interpreting the results should be used, mainly because it is possible that differences in sensitivity of the tests cannot be overcome and because the relative small number of subjects, our results indicate that loprazolam might induce selective impairment of long-term memory. Since there were no differences between the effects on consolidated and non-consolidated memory, the amnesic effect of loprazolam seems to be due to a decrease in the storage of memory traces. There were no clear generalized residual effects in the morning after administration.


Draft Genome Sequence of an International Clonal Lineage 1 Acinetobacter baumannii Strain from Argentina.
In the last few years Acinetobacter baumannii has emerged worldwide as an important nosocomial pathogen in medical institutions. Here, we present the draft genome sequence of the international clonal lineage 1 (ICL1) A. baumannii strain A144 that was isolated in a hospital in Buenos Aires City in the year 1997. The strain is susceptible to carbapenems and resistant to trimethoprim and gentamicin.


Breastfeeding of very low birth weight infants.
This research examines the rate of breastfeeding among mothers of very low birth weight infants (VLBW, < 1500 grams), and the correlates of breast milk pumping and transition to nursing at the breast. Eighty-two mothers and their 69 singleton and 21 twin VLBW infants admitted to the Neonatal Intensive Care Unit (January 1-June 30, 1995) of an urban tertiary care hospital. Maternal demographic, infant birth, and neonatal data were compared according to breast or bottle feeding, and a telephone interview was administered retrospectively to mothers pumping breast milk at the time of the infant's discharge home. Of 39 mothers who chose to pump breast milk, 19 were still pumping at the time of the infant's discharge home. Only 8 made a successful transition to nursing at the breast. Mothers who continued pumping tended to be white, married, and older, and their infants had fewer neonatal complications. The rates of prolonged breast milk pumping and of nursing are very low. Specific interventions and better support might improve the success rates.


Cost effectiveness of antiarrhythmic medications in patients suffering from atrial fibrillation.
Atrial fibrillation (AF), a supraventricular tachycardia disorder, is the most common sustained cardiac arrhythmia affecting 1-2 % of the general population. Prevalence is highly related to age, with every fourth individual older than 40 years old developing AF during his lifetime. Due to an aging population, the prevalence of AF is estimated to at least double within the next 50 years. This article presents AF-related cost-of-illness studies and reviews 19 cost-effectiveness studies and six cost studies published roughly over the past decade, which have compared different antiarrhythmic medications for AF. A systematic literature search for studies published between June 2000 and December 2011 was conducted in PubMed using the combination of keywords ((atrial fibrillation OR atrial flutter) AND cost). Current cost-effectiveness analyses of dronedarone and the pill-in-the-pocket strategy are subject to substantial uncertainties with regard to clinical benefit. Comparing rate control with rhythm control, a cost-effectiveness advantage for rate control was shown in several but not all studies. Within antiarrhythmic drug treatments, magnesium added onto ibutilide was shown to be more cost effective than ibutilide alone. Comparing chemical and electrical cardioversion, the latter was recommended as more cost effective from the healthcare system perspective in all reviewed studies but one. Catheter ablation appeared more cost effective than antiarrhythmic drugs in the medium to long run after 3.2-63.9 years. Admissions to hospital, inpatient care and interventional procedures as well as mortality benefit are key drivers for the cost effectiveness of AF medications. No clear cost-effectiveness advantage emerged for one specific antiarrhythmic drug from the studies that compared antiarrhythmic agents. Rate control as well as catheter ablation appear more cost effective than rhythm control in the treatment of AF. Rate control treatment also seems more cost effective than electrical cardioversion in AF patients.


[Early surgical stabilization of the thorax].
Patients with non-penetrating chest trauma are encountered with increasing frequency. Car crash is the main cause of blunt chest trauma. Despite their nature these lesions may be life-threatening. The mortality rate of chest injuries varies from 20 to 50%. In the last 3 years 86 patients with blunt chest injuries were treated in our institution. 24 patients underwent surgical repair. We compared the outcome of surgical and conservative treatment. Early diagnosis and proper treatment reduce morbidity and mortality.


The role of stream water carbon dynamics and export in the carbon balance of a tropical seasonal rainforest, southwest China.
A two-year study (2009 ~ 2010) was carried out to investigate the dynamics of different carbon (C) forms, and the role of stream export in the C balance of a 23.4-ha headwater catchment in a tropical seasonal rainforest at Xishuangbanna (XSBN), southwest China. The seasonal volumetric weighted mean (VWM) concentrations of total inorganic C (TIC) and dissolved inorganic C (DIC) were higher, and particulate inorganic C (PIC) and organic C (POC) were lower, in the dry season than the rainy season, while the VWM concentrations of total organic C (TOC) and dissolved organic C (DOC) were similar between seasons. With increased monthly stream discharge and stream water temperature (SWT), only TIC and DIC concentrations decreased significantly. The most important C form in stream export was DIC, accounting for 51.8% of the total C (TC) export; DOC, POC, and PIC accounted for 21.8%, 14.9%, and 11.5% of the TC export, respectively. Dynamics of C flux were closely related to stream discharge, with the greatest export during the rainy season. C export in the headwater stream was 47.1 kg C ha(-1) yr(-1), about 2.85% of the annual net ecosystem exchange. This finding indicates that stream export represented a minor contribution to the C balance in this tropical seasonal rainforest.


A family with hemoglobin Hirosaki.
A 48-year-old man had a 30-year history of hemolytic anemia of undetermined cause. Spherocytes were not observed, osmotic fragility was normal, and red cell enzyme activities were normal. His brother and daughter also had hemolytic anemia. The brother had previously undergone splenectomy, and the anemia had been ameliorated. In the proband and daughter, no abnormal hemoglobin was apparent in the results of isoelectric focusing and DEAE anion-exchange high-performance liquid chromatography analyses. On evaluation with the isopropanol test, unstable hemoglobin was not observed in the proband but was detected in the daughter. There was also a decreased ratio of 3 globin/3 globin chain production. Analysis of the 32 gene demonstrated the presence of a mutation (alpha43 [CE1] Phe --> Leu), hemoglobin Hirosaki.


Positive Correlation Between General Public Knowledge and Attitudes Regarding COVID-19 Outbreak 1 Month After First Cases Reported in Indonesia.
The increasing number cases of coronavirus disease (COVID-19) infections in the general population in Indonesia raises questions concerning the public's knowledge and attitudes regarding this pandemic. To determine the correlation between the general public's knowledge and attitudes regarding the COVID-19 outbreak 1 month after the first cases were reported in Indonesia. This cross-sectional study was conducted between early March and the end of April 2020 in the general population of Indonesia, beginning with the North Sumatra region, where the spread of COVID-19 in Indonesia began. Questionnaires were randomly distributed online in the red zone in Indonesia. Data were collected by collecting people's responses to the questionnaire, which were distributed via WhatsApp (WA) application and were competed independently by the participants. A descriptive analysis was conducted to describe the demographic characteristics, knowledge, and attitudes of the general population. A total of 201 people had good knowledge (98%) and a positive attitude (96%) regarding the COVID-19 pandemic. The respondents had a negative attitude in relation to two aspects of the COVID-19 outbreak: having to always maintain a distance of 1.5 m when in crowds, and not being able to regularly exercise or eat nutritious food (78.6% and 79.1%, respectively). Most people in Indonesia have good knowledge and a positive attitude regarding the COVID-19 pandemic. However, negative attitudes were still found in this study, and as a result, transmission prevention measures cannot reach their maximum effectiveness by simply publicizing the increase in day-to-day cases to the general public.


Recent advances in carbon-based materials for high-performance perovskite solar cells: gaps, challenges and fulfillment.
Presently, carbon-based nanomaterials have shown tremendous potential for energy conversion applications. Especially, carbon-based materials have emerged as excellent candidates for the fabrication of halide perovskite-based solar cells, which may lead to their commercialization. In the last decade, PSCs have rapidly developed, and these hybrid devices demonstrate a comparable performance to silicon-based solar cells in terms of power conversion efficiency (PCE). However, PSCs lag behind silicon-based solar cells due to their poor stability and durability. Generally, noble metals such gold and silver are employed as back electrode materials during the fabrication of PSCs. However, the use of these expensive rare metals is associated with some issues, urgently necessitating the search for cost-effective materials, which can realize the commercial applications of PSCs due to their interesting properties. Thus, the present review shows how carbon-based materials can become the main candidates for the development of highly efficient and stable PSCs. Carbon-based materials such as carbon black, graphite, graphene nanosheets (2D/3D), carbon nanotubes (CNTs), carbon dots, graphene quantum dots (GQDs) and carbon nanosheets show potential for the laboratory and large-scale fabrication of solar cells and modules. Carbon-based PSCs can achieve efficient and long-term stability for both rigid and flexible substrates because of their high conductivity and excellent hydrophobicity, thus showing good results in comparison to metal electrode-based PSCs. Thus, the present review also demonstrates and discusses the latest state-of-the-art and recent advances for carbon-based PSCs. Furthermore, we present perspectives on the cost-effective synthesis of carbon-based materials for the broader view of the future sustainability of carbon-based PSCs.


Sex Difference in the Relation Between Marital Status and Dementia Risk in Two Population-Based Cohorts.
The modifying effect of sex on the relation between marital status and dementia has yet to be determined. To examine if sex modifies the association between marital status and incident dementia. Population-based samples from the Mayo Clinic Study of Aging (MCSA, N = 3,471) and the Gothenburg H70 Birth Cohort Study (H70-study, N = 913) were used. A multiplicative interaction term was used to analyze the modifying effect of sex on the relation between marital status (married versus not married) and incident dementia using Cox regression models. Further, risk of dementia by marital status was also evaluated in models separated by sex. In the MCSA, there was an interaction between marital status and sex in relation to dementia (p = 0.015). In contrast, in the H70-study, no significant interaction was observed (p = 0.28). Nevertheless, in both studies, not married men had increased risk of dementia compared to married men in models adjusted for age, education, and number of children (H70-study: 1.99; 1.06-3.76, MCSA: 1.43; 1.08-1.89). Associations remained similar after additional adjustment for depression, BMI, hypertension, dyslipidemia, and diabetes mellitus (H70-study: 2.00; 1.05-3.82, MCSA: 1.32; 0.99-1.76). Further, no significant association was observed between marital status and dementia in women (H70-study: 1.24; 0.82-1.89, MCSA: 0.82; 0.64-1.04). Sex had a modifying effect on the association between marital status and incident dementia. In analyses separated by sex, not married men had an increased risk of dementia compared to married men, while no significant association was observed between marital status and risk of dementia in women.


TNF receptor-deficient mice reveal striking differences between several models of thymocyte negative selection.
Central tolerance depends upon Ag-mediated cell death in developing thymocytes. However, the mechanism of induced death is poorly understood. Among the known death-inducing proteins, TNF was previously found to be constitutively expressed in the thymus. The role of TNF in thymocyte negative selection was therefore investigated using TNF receptor (TNFR)-deficient mice containing a TCR transgene. TNFR-deficient mice displayed aberrant negative selection in two models: an in vitro system in which APC are cultured with thymocytes, and a popular in vivo system in which mice are treated with anti-CD3 Abs. In contrast, TNFR-deficient mice displayed normal thymocyte deletion in two Ag-induced in vivo models of negative selection. Current models of negative selection and the role of TNFR family members in this process are discussed in light of these results.


The first proandric species of Tritogenia Kinberg, 1867 from Botswana, Tritogenia talana sp.n. (Clitellata, Crassiclitellata, Tritogeniidae).
The earthworm fauna of Botswana is hitherto unknown. A first collecting trip to the regions of Chobe and Tuli Block resulted in the discovery of a new species, Tritogenia talana sp.n. Its reproductive organs show some level of degeneration when compared to other species of Tritogenia. The spermathecae were not observed, testes and sperm funnels are in proandric condition and seminal vesicles are absent. This is the first record of an earthworm species from Botswana.


[Multi-wall orbital decompression for disfiguring proptosis in patients with mild or moderate thyroid eye disease].
Objective: To evaluate the efficacy of orbital decompression by transconjunctival medial and inferior wall combined transpalpebral lateral wall for disfiguring proptosis with mild or moderate thyroid eye disease (TED). Methods: It is a retrospective case series study. The clinical data of 18 TED cases (28 orbits) between Dec 2013 and Dec 2015 at the Institute of Orbital Diseases of the General Hospital of the Armed Police were reviewed. All the patients underwent mulit-wall orbital decompression to relieve remarkable proptosis, widen eyelid fissure, and swollen eyelid. 1. Hertel value was 14-23 mm or over 2-7 mm than contralateral eye; 2.Orbitalpathy has been inactive with normal thyroid function for at least 6 months; 3.Orbital pressure is normal or (+). Clinical outcomes were recorded including best-corrected visual acuity, exophthalmometry, margin-to-central distance of upper and lower lids, diplopia, and CT scans before and 3 months after surgery. Results: The mean protosis of pre-and postoperation were (19.2±2.3) mm and (14.7±1.4) mm with mean reduction was (4.6±1.7) mm (t=14.08, P<0.01). Margin-to-central distance of the upperlid of pre- and postoperation were (5.1±1.2) mm and (4.9±1.3) mm with mean reduction was (0.2±0.5) mm (t=1.73, P=0.095). Margin-to-central distance of the lowerlid of pre-and postoperation were (5.9±0.9) mm and 4.3±0.7 mm with mean reduction was (1.6±0.8) mm (t=10.09, P<0.01). The difference of bilateral exophthalmos after surgery is 0-2.5 mm (median=1 mm). None of the patients showed new-onset diplopia at primary gaze and two patient showed surrounding gaze diplopia postoperatively. Two patients with diplopia relieved after surgery (Z=743.00, P=0.458). Conclusions: Transconjunctival and transpalpebral medial, inferior, and lateral walls decompression with a hidden incision was a controllable, safe, effective technique with minimal complications in relieving not only mild, moderate proptosis, but also retraction of lowerlid, and swollen eyelids. (Chin J Ophthalmol, 2017, 53: 128-135).


Lichen Vitality After a Space Flight on Board the EXPOSE-R2 Facility Outside the International Space Station: Results of the Biology and Mars Experiment.
As part of the Biology and Mars Experiment (BIOMEX; ILSRA 2009-0834), samples of the lichen Circinaria gyrosa were placed on the exposure platform EXPOSE-R2, on the International Space Station (ISS) and exposed to space and to a Mars-simulated environment for 18 months (2014-2016) to study: (1) resistance to space and Mars-like conditions and (2) biomarkers for use in future space missions (Exo-Mars). When the experiment returned (June 2016), initial analysis showed rapid recovery of photosystem II activity in the samples exposed exclusively to space vacuum and a Mars-like atmosphere. Significantly reduced recovery levels were observed in Sun-exposed samples, and electron and fluorescence microscopy (transmission electron microscope and field emission scanning electron microscope) data indicated that this was attributable to the combined effects of space radiation and space vacuum, as unirradiated samples exhibited less marked morphological changes compared with Sun-exposed samples. Polymerase chain reaction analyses confirmed that there was DNA damage in lichen exposed to harsh space and Mars-like environmental conditions, with ultraviolet radiation combined with space vacuum causing the most damage. These findings contribute to the characterization of space- and Mars-resistant organisms that are relevant to Mars habitability.


Steiner minimal trees, twist angles, and the protein folding problem.
The Steiner Minimal Tree (SMT) problem determines the minimal length network for connecting a given set of vertices in three-dimensional space. SMTs have been shown to be useful in the geometric modeling and characterization of proteins. Even though the SMT problem is an NP-Hard Optimization problem, one can define planes within the amino acids that have a surprising regularity property for the twist angles of the planes. This angular property is quantified for all amino acids through the Steiner tree topology structure. The twist angle properties and other associated geometric properties unique for the remaining amino acids are documented in this paper. We also examine the relationship between the Steiner ratio rho and the torsion energy in amino acids with respect to the side chain torsion angle chi(1). The rho value is shown to be inversely proportional to the torsion energy. Hence, it should be a useful approximation to the potential energy function. Finally, the Steiner ratio is used to evaluate folded and misfolded protein structures. We examine all the native proteins and their decoys at http://dd.stanford.edu. and compare their Steiner ratio values. Because these decoy structures have been delicately misfolded, they look even more favorable than the native proteins from the potential energy viewpoint. However, the rho value of a decoy folded protein is shown to be much closer to the average value of an empirical Steiner ratio for each residue involved than that of the corresponding native one, so that we recognize the native folded structure more easily. The inverse relationship between the Steiner ratio and the energy level in the protein is shown to be a significant measure to distinguish native and decoy structures. These properties should be ultimately useful in the ab initio protein folding prediction.


The crystal structure of Arabidopsis BON1 provides insights into the copine protein family.
The Arabidopsis thaliana BON1 gene product is a member of the evolutionary conserved eukaryotic calcium-dependent membrane-binding protein family. The copine protein is composed of two C2 domains (C2A and C2B) followed by a vWA domain. The BON1 protein is localized on the plasma membrane, and is known to suppress the expression of immune receptor genes and to positively regulate stomatal closure. The first structure of this protein family has been determined to 2.5-Å resolution and shows the structural features of the three conserved domains C2A, C2B and vWA. The structure reveals the third Ca2+ -binding region in C2A domain is longer than classical C2 domains and a novel Ca2+ binding site in the vWA domain. The structure of BON1 bound to Mn2+ is also presented. The binding of the C2 domains to phospholipid (PSF) has been modeled and provides an insight into the lipid-binding mechanism of the copine proteins. Furthermore, the selectivity of the separate C2A and C2B domains and intact BON1 to bind to different phospholipids has been investigated, and we demonstrated that BON1 could mediate aggregation of liposomes in response to Ca2+ . These studies have formed the basis of further investigations into the important role that the copine proteins play in vivo.


Cloning, expression, purification, crystallization and preliminary X-ray diffraction analysis of intracellular growth locus E (IglE) protein from Francisella tularensis subsp. novicida.
Tularaemia is an uncommon but potentially dangerous zoonotic disease caused by the bacterium Francisella tularensis. As few as ten bacterial cells are sufficient to cause disease in a healthy human, making this one of the most infectious disease agents known. The virulence of this organism is dependent upon a genetic locus known as the Francisella pathogenicity island (FPI), which encodes components of a secretion system that is related to the type VI secretion system. Here, the cloning, expression, purification and preliminary X-ray diffraction statistics of the FPI-encoded protein IglE are presented. This putative lipoprotein is required for intra-macrophage growth and is thought to be a constituent of the periplasmic portion of the type VI-like protein complex that is responsible for the secretion of critical virulence factors in Francisella.


Thrombocytopenia, Platelet Transfusion, and Outcome Following Liver Transplantation.
Thrombocytopenia affects patients undergoing liver transplantation. Intraoperative platelet transfusion has been shown to independently influence survival after liver transplantation at 1 and 5 years. We examined the impact of thrombocytopenia and intraoperative platelet transfusion on short-term graft and overall survival after orthotopic liver transplantation (OLT). A total of 399 patients undergoing first OLT were studied. Graft and overall survival in patients with different degrees of thrombocytopenia and with or without intraoperative platelet transfusion were described. The degree of thrombocytopenia prior to OLT did not affect graft or overall survival after transplant. However, graft survival in patients receiving platelets was significantly reduced at 1 year (P= .023) but not at 90 days (P= .093). Overall survival was significantly reduced at both 90 days (P= .040) and 1 year (P= .037) in patients receiving platelets. We conclude that a consistently lower graft and overall survival were observed in patients receiving intraoperative platelet transfusion.


Radiofrequency catheter ablation of a left lateral accessory pathway in a patient with persistent left superior vena cava.
Persistent left superior vena cava is an unusual congenital anomaly that can coexist with accessory atrioventricular pathways. This anomaly can cause difficulty in mapping because of the dilated coronary sinus. This study describes a successful catheter ablation in a young male with persistent left superior vena cava and Wolff-Parkinson-White Syndrome as a result of a left lateral accessory pathway.


Alteration in the Local and Global Functional Connectivity of Resting State Networks in Parkinson's Disease.
Parkinson's disease (PD) is a neurodegenerative disorder that mainly leads to the impairment of patients' motor function, as well as of cognition, as it progresses. This study tried to investigate the impact of PD on the resting state functional connectivity of the default mode network (DMN), as well as of the entire brain. Sixty patients with PD were included and compared to 60 matched normal control (NC) subjects. For the local connectivity analysis, the resting state fMRI data were analyzed by seed-based correlation analyses, and then a novel persistent homology analysis was implemented to examine the connectivity from a global perspective. The functional connectivity of the DMN was decreased in the PD group compared to the NC, with a stronger difference in the medial prefrontal cortex. Moreover, the results of the persistent homology analysis indicated that the PD group had a more locally connected and less globally connected network compared to the NC. Our findings suggest that the DMN is altered in PD, and persistent homology analysis, as a useful measure of the topological characteristics of the networks from a broader perspective, was able to identify changes in the large-scale functional organization of the patients' brain.


Interaction of human organic anion transporters 2 and 4 with organic anion transport inhibitors.
The organic anion transport system is involved in the tubular excretion and reabsorption of various drugs and substances. The purpose of this study was to characterize the effects of various organic anion transport inhibitors on renal organic anion transport using proximal tubule cells stably expressing human organic anion transporter 2 (hOAT2) and hOAT4. Immunohistochemical analysis revealed that hOAT2 is localized to the basolateral side of the proximal tubule in the kidney. hOAT2 mediated a time- and concentration-dependent increase in prostaglandin F(2alpha) (PGF(2alpha)) uptake. The organic anion transport inhibitors used for this study were probenecid, 8-(noradamantan-3-yl)-1,3-dipropylxanthine (KW-3902), betamipron, and cilastatin. Probenecid, but not KW-3902, betamipron, and cilastatin, significantly inhibited hOAT2-mediated PGF(2alpha) uptake. In contrast, probenecid, KW-3902, and betamipron, but not cilastatin, inhibited hOAT4-mediated estrone sulfate (ES) uptake. Kinetic analyses revealed that these inhibitions were competitive. The K(i) value of probenecid for hOAT2 was 766 microM, whereas those of probenecid, KW-3902, and betamipron for hOAT4 were 54.9, 20.7, and 502 microM, respectively. These results suggest that probenecid, KW-3902, and betamipron could inhibit hOAT4-mediated ES uptake in vitro, whereas probenecid alone could inhibit the hOAT2-mediated PGF(2alpha) uptake. Comparing the K(i) values with the therapeutically relevant concentrations of unbound inhibitors in the plasma, probenecid alone was predicted to inhibit hOAT4-mediated organic anion transport in vivo.


Groundwater hydrogeochemistry and non-carcinogenic health risk assessment in major river basins of Punjab, India.
The Indian Punjab state is drained by the four rivers, along with a well-connected network of canals, and is now dealing with a slew of water quality issues and problems. In this study, basin-wise hydrogeochemical modelling of 323 groundwater samples and identification of NO3- and F- enrichment pathways in aquifer systems of Punjab were studied using different plots and multivariate statistics. To evaluate the groundwater quality and human health risks, an entropy-based water quality index and Monte Carlo simulation were used, respectively. Spatial distribution of NO3- indicated that its very high values were prominent in parts of southwestern Punjab falling under LSRB, along with few pockets in eastern and northeastern Punjab falling under MSRB and GRB. High NO3- values (> 45.0 mg/L) were found in 15.0% of Ravi River Basin (RRB) groundwater samples, 22.86% of Beas River Basin (BRB), 23.52% of Middle Sutlej River Basin (MSRB), 36.9% of Lower Sutlej River Basin (LSRB), and 21.31% of Ghaggar River Basin (GRB). The spatial distribution of NO3- revealed elevated concentrations (> 100 mg/L) in the southwestern part of Punjab, particularly in LSRB and localized pockets in the eastern and northeastern areas of Punjab within MSRB and GRB. High F- concentration (> 1.5 mg/L) was observed in 15.12% and 21.31% groundwater samples of LSRB and GRB, respectively. Spatially southern parts falling under LSRB and GRB reflected high F- content (> 1.5 mg/L) in groundwater. In LSRB, evaporative and anthropogenic processes influence the groundwater quality. The results of interionic relationships and statistical analysis revealed that NO3- has anthropogenic origin and that is being aggravated by leaching, the evaporation processes, animal excreta, septic tanks and irrigation return flows in LSRB and GRB, while F- is geogenic in nature. Hazard index (HI) values in 14.63%, 22.2%, 24.6%, 49.58%, and 34.42% samples for adults and 21.95%, 27.7%, 42.0%, 72.3%, and 52.46% samples for children were higher than unity in RRB, BRB, MSRB, LSRB, and GRB, respectively. The basin-wise demarcation of various groundwater quality parameter and assessment of human health risk would be of significance for the management of water resources.


[Incidents of cutaneous alteration secondary to external electrical cardioversion].
External electrical cardioversion is a technique basically used as treatment of choice in supraventricular arrhythmias, atrial fibrillation standing out for its frequency. This procedure consists in the application of one or several synchronized electrical discharges through the patient's chest to revert cardiac rhythm to sinus rhythm. One of the complications is generally the appearance of the skin alterations, pain or intense local heat. The objectives of this study were to describe the skin lesions that appeared after an external electrical cardioversion procedure and to evaluate the information received by the patients on discharge. A descriptive study was conducted, using a sample of 68 patients who underwent cardioversion between January 1 and December 30 1, 2004. Mean age was 62.71 years, of which 76.5% were males diagnosed of atrial fibrillation in 82.4% of the cases. Erythema appeared in more than 80% of the cases, with the mean duration of 4.76 days. A total of 13.2% developed second-degree burn. Although 92.5% considered written information on the care after the procedure necessary, less than 11% had received it. It is concluded that the prevalence of the skin alterations after cardioversion is elevated, one of the causal factors being lack of information. There is a significant deficiency of knowledge on skin care after the procedure.


Comparative evaluation of Brassica oleracea, Ocimum basilicum, and Moringa oleifera leaf extracts on lipase inhibition and adipogenesis in 3T3-L1 adipocytes.
The anti-adipogenic effects of alcohol extract of Brassica oleracea (BO), Ocimum basilicum (OB), and Moringa oleifera (MO) leaves on 3T3-L1 pre-adipocyte as well as their lipase inhibitory properties were comparatively evaluated. The polyphenol-rich extracts of MO, BO, and OB leaves were profiled for major bioactive compounds using UPLC-HRMS/MS analysis. Among the three plant extracts, BO had the highest flavonoid content with stronger radical scavenging activity. All extracts exhibited lipase inhibitory activities, dose-dependently and a non-competitive type of inhibition with altered kinetic parameters was observed. In cell culture studies, these plant extracts remarkably inhibited the intracellular triglyceride accumulation in 3T3-L1 cells and the effect was in the decreasing order of BO > OB > MO. The extracts also down-regulated the key transcription factors of adipogenesis (PPARγ, C/EPB-α, PI3k, p-Akt, and FAS enzyme) as well as modulated the release profile of leptin and adiponectins. Overall, BO extract showed an exceptional inhibitory potential against both adipogenesis and lipase activities among the evaluated plants. PRACTICAL APPLICATIONS: The present study highlights the anti-adipogenic potential of three local edible plants and herbs, that is, Brassica oleracea (BO), Ocimum basilicum (OB), and Moringa oleifera (MO) leaves, using in vitro models. The results revealed that the BO extract had remarkable activity against adipogenesis in the 3T3-L1 pre-adipocyte differentiation model as well as lipase inhibitory properties. This study elucidates the prospects of natural plant-derived compounds in managing obesity-related health issues. The outcomes of this study would be useful in developing alternative or complementary therapies that are being preferred and largely sought over pharmacological treatments and procedures for controlling and treating abnormal weight gain in humans.


Radical 1,2-aryl migration in α,α-diaryl allylic alcohols toward β-silyl ketones.
A copper-catalyzed radical 1,2-aryl migration in α,α-diaryl allylic alcohols is developed, leading to β-silyl carbonyl compounds in moderate to good yields. The migration of aryls with lower aromaticity is favored. This procedure features the employment of silanes as commercially available materials.


Reaction Mechanisms of the Atomic Layer Deposition of Tin Oxide Thin Films Using Tributyltin Ethoxide and Ozone.
Uniform and conformal deposition of tin oxide thin films is important for several applications in electronics, gas sensing, and transparent conducting electrodes. Thermal atomic layer deposition (ALD) is often best suited for these applications, but its implementation requires a mechanistic understanding of the initial nucleation and subsequent ALD processes. To this end, in situ FTIR and ex situ XPS have been used to explore the ALD of tin oxide films using tributyltin ethoxide and ozone on an OH-terminated, SiO2-passivated Si(111) substrate. Direct chemisorption of tributyltin ethoxide on surface OH groups and clear evidence that subsequent ligand exchange are obtained, providing mechanistic insight. Upon ozone pulse, the butyl groups react with ozone, forming surface carbonate and formate. The subsequent tributyltin ethoxide pulse removes the carbonate and formate features with the appearance of the bands for CH stretching and bending modes of the precursor butyl ligands. This ligand-exchange behavior is repeated for subsequent cycles, as is characteristic of ALD processes, and is clearly observed for deposition temperatures of 200 and 300 °C. On the basis of the in situ vibrational data, a reaction mechanism for the ALD process of tributyltin ethoxide and ozone is presented, whereby ligands are fully eliminated. Complementary ex situ XPS depth profiles confirm that the bulk of the films is carbon-free, that is, formate and carbonate are not incorporated into the film during the deposition process, and that good-quality SnOx films are produced. Furthermore, the process was scaled up in a cross-flow reactor at 225 °C, which allowed the determination of the growth rate (0.62 Å/cycle) and confirmed a self-limiting ALD growth at 225 and 268 °C. An analysis of the temperature-dependence data reveals that growth rate increases linearly between 200 and 300 °C.


MIRACLE: Mobility Prediction Inside a Coverage Hole Using Stochastic Learning Weak Estimator.
In target tracking applications of wireless sensor networks (WSNs), one of the important but overlooked issues is the estimation of mobility behavior of a target inside a coverage hole. The existing approaches are restricted to networks with effective coverage by wireless sensors. Additionally, those works implicitly considered that a target does not change its mobility pattern inside the entire tracking region. In this paper, we address the above lacunae by designing a stochastic learning weak estimation-based scheme, namely mobility prediction inside a coverage hole (MIRACLE). The objectives of MIRACLE are two fold. First, one should be able to correctly predict the mobility pattern of a target inside a coverage hole with low computational overhead. Second, if a target changes its mobility pattern inside the coverage hole, the proposed estimator should give some estimation about all possible transitions among the mobility models. We use the trajectory extrapolation and fusion techniques for exploring all possible transitions among the mobility models. We validate the results with simulated traces of mobile targets generated using network simulator NS-2. Simulation results show that MIRACLE estimates the mobility patterns inside coverage hole with an accuracy of more than 60% in WSNs.


2D electron density profile measurement in tokamak by laser-accelerated ion-beam probe.
A new concept of Heavy Ion Beam Probe (HIBP) diagnostic has been proposed, of which the key is to replace the electrostatic accelerator of traditional HIBP by a laser-driven ion accelerator. Due to the large energy spread of ions, the laser-accelerated HIBP can measure the two-dimensional (2D) electron density profile of tokamak plasma. In a preliminary simulation, a 2D density profile was reconstructed with a spatial resolution of about 2 cm, and with the error below 15% in the core region. Diagnostics of 2D density fluctuation is also discussed.


Arrhythmogenic right ventricular dysplasia.
Arrhythmogenic right ventricular dysplasia (ARVD) is an inherited cardiomyopathy and is also called ARVD/C. In most cases, ARVD is inherited in an autosomal-dominant pattern and clinically is characterized by ventricular arrhythmias with an increased risk of sudden death. Although it is prominently a disease of the right ventricle (RV), involvement of the left ventricle is not uncommon. Pathologically, there is RV myocardial atrophy with thinning of the wall, aneurysm, and global RV dilatation. Genetic testing and magnetic resonance imaging of the RV are an increasing aspect of the diagnosis. Diagnosis relies on a scoring system with major or minor criteria. Prevention of sudden death is the primary goal of management. Pharmacologic treatment of arrhythmias, catheter ablation of ventricular tachycardia, and implantable cardioverter defibrillator are the mainstay of treatment of ARVD/C.


Cytoprotective Mechanisms in Fatty Liver Preservation against Cold Ischemia Injury: A Comparison between IGL-1 and HTK.
Institute Goeorges Lopez 1 (IGL-1) and Histidine-Tryptophan-Ketoglutarate (HTK) preservation solutions are regularly used in clinical for liver transplantation besides University of Wisconsin (UW) solution and Celsior. Several clinical trials and experimental works have been carried out comparing all the solutions, however the comparative IGL-1 and HTK appraisals are poor; especially when they deal with the underlying protection mechanisms of the fatty liver graft during cold storage. Fatty livers from male obese Zücker rats were conserved for 24 h at 4 °C in IGL-1 or HTK preservation solutions. After organ recovery and rinsing of fatty liver grafts with Ringer Lactate solution, we measured the changes in mechanistic target of rapamycin (mTOR) signaling activation, liver autophagy markers (Beclin-1, Beclin-2, LC3B and ATG7) and apoptotic markers (caspase 3, caspase 9 and TUNEL). These determinations were correlated with the prevention of liver injury (aspartate and alanine aminostransferase (AST/ALT), histology) and mitochondrial damage (glutamate dehydrogenase (GLDH) and confocal microscopy findings). Liver grafts preserved in IGL-1 solution showed a marked reduction on p-TOR/mTOR ratio when compared to HTK. This was concomitant with significant increased cyto-protective autophagy and prevention of liver apoptosis, including inflammatory cytokines such as HMGB1. Together, our results revealed that IGL-1 preservation solution better protected fatty liver grafts against cold ischemia damage than HTK solution. IGL-1 protection was associated with a reduced liver damage, higher induced autophagy and decreased apoptosis. All these effects would contribute to limit the subsequent extension of reperfusion injury after graft revascularization in liver transplantation procedures.


Are the Pathological Characteristics of Prostate Cancer More Aggressive or More Indolent Depending upon the Patient Age?
Purpose. To identify pathological characteristics of prostate cancer according to patient age at diagnosis. Methods. A retrospective review of 2,929 men diagnosed with prostate cancer was performed. Pathological characteristics were compared across age groups: ≤55, 56-75, and >75 years. Results. The study cohort included 133 patients (4.5%), 2,033 patients (69.5%), and 763 patients (26.0%) in the three age groups, respectively. The median pathological Gleason sums in the three age groups were 8, 7, and 8, respectively. The Gleason sum, primary Gleason score, and second primary Gleason score were significantly different among the three age groups (Z = 12.975, p = 0.002; Z = 9.264, p = 0.010; Z = 6.692, p = 0.035, resp.). The percentages of Gleason pattern 5 tumors for the three age groups were 44.4%, 32.3%, and 36.8%, respectively; they were significantly different (χ2 = 11.641, p = 0.003). The percentages of tumors with Gleason score grade groups 3-5 for the three age groups were 66.9%, 60.5%, and 66.3%, respectively; they were significantly different (χ2 = 9.401, p = 0.009). Conclusions. The present study indicated that men aged ≤55 years or >75 years show higher levels of clinically significant prostate cancer compared to patients between the ages of 55 and 75 years. Younger and more elderly male patients are more likely to have a more aggressive disease.


Hypotensive action and alpha-adrenolytic properties of a new dopaminergic agonist, CU 32-085, in the rat.
The effect of an 8-alpha-amino-ergoline-derivative, CU 32-085, recently characterized as a dopamine agonist, was studied on blood pressure and heart rate in normotensive anesthetized rats. The effects of CU 32-085 and bromocriptine on dose-response curves to sympathomimetic agents (adrenaline, noradrenaline, methoxamine and clonidine), intravenously administered, were also studied. CU 32-085 slowed heart rate and lowered blood pressure. The hypotensive effect was antagonized by pretreatment with sulpiride. CU 32-085 and bromocriptine reduced the pressor effect of adrenaline, noradrenaline and methoxamine and the hypotensive action of clonidine. These results suggest that the hypotensive action of CU 32-085, like bromocriptine, is mainly due to an action on dopaminergic receptors. In addition, the data obtained with sympathomimetic agents suggest that CU 32-085 is a compound with mixed alpha 1 and alpha 2 antagonist properties, similar to bromocriptine.


Human glomerular growth during childhood: a morphometric study.
Morphometric measurements of glomerular size were made on renal biopsy specimens obtained from 16 children with minimal change nephrotic syndrome (MCNS) and 16 with isolated recurrent haematuria (RH), whose ages ranged from 1.8 to 15.2 years. Glomeruli were normal on light and electron microscopy, and immunofluorescence was essentially negative. Tracings were made of the outlines of glomerular capsules, tufts, and individual capillary lumens; using computerized digitometry, the mean areas of each item were determined. The number of capillary lumens per glomerulus was counted automatically. From these data, the mean mesangial area was also calculated. Mesangial cells were counted in at least 100 distal mesangial areas per biopsy. The mean glomerular capsular area (GCA) correlated well with the mean glomerular tuft area (GTA) but frequent capsular artefacts rendered the former measurement less suitable for comparison with diseased glomeruli. The mean GTA correlated significantly with age and body surface area in both MCNS and RH, as did the number of capillary lumens per glomerulus, but the mean capillary lumina area showed no such correlations. The mean mesangial area increased with age in proportion to GTA, whereas mesangial cell counts remained normal. These findings indicate that glomerular growth during childhood is proportional to body growth, and are consistent with capillary subdivision as the mechanism of enlargement.


Troponin T and N-terminal pro-brain natriuretic peptide changes in patients undergoing transurethral resection of the prostate.
We investigated whether transurethral resection of the prostate (TURP) caused subclinical myocardial damage or cardiac dysfunction by measuring troponin T (Trop T) and N-terminal pro-brain natriuretic peptide (pro-BNP). A total of 52 consenting patients took part in this study. All had a detailed medical history including cardiac history taken. On the day of the operation all patients had troponin T, pro-BNP, full blood count and urea, electrolytes and creatinine measured preoperatively. A preoperative and postoperative electrocardiogram was performed. Patients in renal failure were excluded from analysis. During the operations factors such as blood loss, operative time, tissue resected and fluid absorption were monitored. On postoperative day 1 all the previously mentioned tests were repeated. Mean patient age was 71 years (range 52 to 85). Eight patients had a history of associated cardiac problems. Mean preoperative and postoperative hemoglobin were 14.1 gm/dl (range 10.5 to 17) and 13.3 gm/dl (range 9.9 to 16.2), respectively. None of the patients had significant (greater than 1,000 ml) fluid absorption during TURP, which was calculated using ethanol tagged glycine. Mean blood loss measured with a photometer was 129.7 ml (range 0 to 1,800). Mean operative time was 28.4 minutes (range 5 to 50) and mean weight of prostatic tissue resected was 15.2 gm (range 1 to 47). Preoperative Trop T was less than 0.01 mcg/ml in all patients and mean pro-BNP was 39.2 pg/ml (range 0.5 to 866). Postoperative Trop T was less than 0.01 mcg/ml in all but 1 patient who experienced chest pain after TURP and had an increased Trop T (0.28 mcg/ml). Mean postoperative pro-BNP was 54.57 pg/ml (range 1 to 679). A total of 37 patients had an increase in pro-BNP which was still within the reference range for the age group. There were no significant electrocardiogram changes postoperatively. The Trop T changes were not statistically significant (Wilcoxon sign ranked test p = 0.31) although they may be clinically significant. Our study indicates that in patients with no prior cardiac history TURP does not cause myocardial damage indicated by nonincrease of Trop T. There are slight increases in pro-BNP after TURP in some patients although the exact clinical significance is uncertain.


General practitioner trainees' in-consultation generation of clinical questions for later answering: prevalence and associations.
As well as generating patient-specific questions, patient consultations are a rich source of questions relating to clinicians' need to acquire or maintain wider clinical knowledge. This is especially so for GP trainees. To establish the prevalence and associations of GP trainees' generation of 'learning goals' (LGs: questions generated during clinical consultations for intended post-consultation answering). Also, to characterize the type of learning goals generated. A cross-sectional analysis (2010-15) of an ongoing cohort study of Australian GP trainees' consultations. Once each 6-month training term, trainees record detailed data of 60 consecutive consultations. The primary outcome was generation of an LG. Analysis was at the level of individual problem/diagnosis managed. The secondary outcome was the problems/diagnoses to which the LGs related. One thousand one hundred and twenty-four trainees contributed data for 154746 consultations including 222307 problems/diagnoses. LGs were generated for 16.6% [95% confidence intervals (CI) = 16.4-16.7] of problems/diagnoses, in 22.1% (95% CI = 21.9-22.3%) of consultations. Associations of LGs included patient factors: younger age and having seen the trainee previously; trainee factors: earlier training stage, being overseas-trained and the trainee's training organization; consultation factors: longer duration, addressing a chronic disease, referring the patient, organizing follow-up, organizing investigations and accessing in-consultation information. LGs were commonly generated for skin (12.9% of all learning goals), musculoskeletal (12.7%) and respiratory (8.7%) problems. LGs were generated for 31.8% of male genital, 27.0% of neurological and 23.3% of eye problems. Australian GP trainees frequently generate questions in-consultation to be pursued post-consultation. Prevalence, 'complexity' and familiarity of clinical topic area influenced LG generation.


Phase I and pharmacokinetic study of etaracizumab (Abegrin), a humanized monoclonal antibody against alphavbeta3 integrin receptor, in patients with advanced solid tumors.
This study assessed the safety, immunogenicity, and pharmacokinetics of etaracizumab, a monoclonal antibody directed against the alphavbeta3 integrin, in patients with advanced malignancies. Four cohorts of four patients received escalating dose of etaracizumab as a 30-min intravenous infusion, first as a single test dose, followed-up 2-5 weeks later by weekly doses. Sixteen patients with advanced solid tumors received a total of 309 cycles of etaracizumab at doses ranging 1-6 mg/kg. The mean number of weekly infusions was 19 (ranging 5-53). Frequently reported adverse events were grades 1-2 asthenia (15 patients) and infusion reactions (9 patients). At 1 mg/kg, one patient experienced grade 3 chills with the first infusion. Other grade 3 toxicities included reversible hyponatremia, hypophosphatemia and hyponatremia in one patient each at 1, 4 and 6 mg/kg, respectively. No patient experienced treatment delay/discontinuation due to an adverse event. The half-life of etaracizumab ranged 49-180 h with a nonlinear increase in terminal half-life with increasing doses. There was no objective response but five patients experienced a stable disease of >6-month duration. Etaracizumab was well-tolerated at doses up to 6 mg/kg with no evidence of immunogenicity. The safety profile of etaracizumab warrants further exploration in ongoing phase I/II trials.


Measurement of refractive index of hemoglobin in the visible/NIR spectral range.
This study is focused on the measurements of the refractive index of hemoglobin solutions in the visible/near-infrared (NIR) spectral range at room temperature for characteristic laser wavelengths: 480, 486, 546, 589, 644, 656, 680, 930, 1100, 1300, and 1550 nm. Measurements were performed using the multiwavelength Abbe refractometer. Aqua hemoglobin solutions of different concentrations obtained from human whole blood were investigated. The specific increment of refractive index on hemoglobin concentration and the Sellmeier coefficients were calculated.