Structure and transmembrane nature of the acetylcholine receptor in amphibian skeletal muscle as revealed by cross-reacting monoclonal antibodies.
A collection of 126 monoclonal antibodies (mAbs) made against acetylcholine receptors (AChRs) from the electric organs of Torpedo californica or Electrophorus electricus was tested for cross-reactivity with AChRs in cryostat sections of skeletal muscle from Rana pipiens and Xenopus laevis by indirect immunofluorescence. 49 mAbs (39%) cross-reacted with AChRs from Rana, and 25 mAbs (20%) cross-reacted with AChRs from Xenopus. mAbs specific for each of the four subunits of electric organ AChR (alpha, beta, gamma, delta) cross-reacted with AChRs from each amphibian species. mAbs cross-reacting with Xenopus AChRs were, with one exception, a subset of the mAbs cross-reacting with Rana AChRs. The major difference detected between the two species was in binding by mAbs specific for the main immunogenic region (MIR) of the alpha-subunit. Whereas 22 of 33 anti-MIR mAbs tested cross-reacted with Rana AChRs, only one of these mAbs cross-reacted with Xenopus AChRs. Some (32) of the cross-reacting mAbs were tested for binding to AChRs in intact muscle. 21 of these mAbs bound to AChRs only when membranes were made permeable with saponin. Electron microscopy using immunoperoxidase or colloidal gold techniques revealed that these mAbs recognize cytoplasmic determinants and that mAbs that do not require saponin in order to bind AChRs in intact muscle recognize extracellular determinants. These results suggest that AChRs in skeletal muscle of Rana and Xenopus are composed of subunits corresponding to the alpha-, beta-, gamma-, and delta-subunits of AChRs from fish electric organs. The subunit specificity of mAbs whose binding was examined by electron microscopy suggests that parts of each subunit (alpha, beta, gamma, delta) are exposed on the cytoplasmic surface and that, as in AChRs from fish electric organs and mammalian muscle, the MIR on alpha-subunits of Rana AChRs is exposed on the extracellular surface.


Wearing Off Response to OnabotulinumtoxinA in Chronic Migraine: Analysis in a Series of 193 Patients.
Long-term real-life studies have supported a cumulative effect of OnabotulinumtoxinA (OnabotA) for the prophylactic treatment of chronic migraine (CM) during consecutive cycles, and individual adaptations have been described to improve clinical response. This was a cohort longitudinal retrospective study of consecutive adult patients from the Headache Unit of the Hospital Clínico Universitario de Valladolid and the Hospital Universitario de La Princesa (Madrid) on OnabotA treatment for chronic migraine from May 2012 to December 2017. All patients were followed for 24 weeks. Full-length response to OnabotA was defined as ≥50% reduction in headache days for at least 12 weeks, and wearing off response was defined as a clinical response but with duration shorter than 10 weeks. We have analyzed the incidence and clinical predictors of this wearing off response. A total of 193 patients were included, of whom 91 (47.1%) were considered full-length responders and 45 (23.3%) wearing off responders. No statistically significant clinical predictors (including demographic variables and baseline headache characteristics) of full-length response or wearing off response were detected in our study. An increase in dose during the second treatment cycle was attempted in 68.9% of the wearing off patients, achieving a longer duration of response of up to 12 weeks in 74.2%. Wearing off response to OnabotA during the first treatment cycle is not uncommon in patients with CM. Increasing the dose in subsequent cycles could improve clinical response, but further multicenter long-term studies are needed to establish predictors and solutions to this problem.


[Treatment of patients with rheumatoid arthritis who desire to become pregnant--successful pregnancy in three cases treated with etanercept].
We report 3 cases with rheumatoid arthritis (RA) who successfully gave birth just after etanercept was introduced for the treatment of RA. All of them had worried about infertility for a long time. It is difficult to confirm the safety of any medication during pregnancy. We sometimes hear that patients stop their medicines owing to the fear of side effects, such as birth defects; this fear is especially prevalent for disease modifying antirheumatic drugs (DMARDs). But it often takes a long time before women can become pregnant after discontinuation of DMARDs, and the activity of RA could become worse during this period. During this period, patients tend to take nonsteroidal anti-inflammatory drugs, which is not recommended during infertility. Etanercept has never been shown to be teratogenic in either animals or humans. We propose that etanercept may be a suitable drug for patients with RA who desire to become pregnant.


An experience of ischemic limb salvage associated with myositis ossificans of the left thigh.
A case of ischemic limb salvage associated with myositis ossificans of the left thigh in a 66-year-old man was reported. The patient had a medical history of cerebral palsy and a cervical spinal cord injury, and had an operative past history of hip arthroplasty for fracture of the left femoral neck 10 years before. He showed ischemic symptoms such as paleness, coldness, and loss of the left dorsal arterial pulsation in the left toe, and had a rapidly growing mass in the left thigh. Roentgenography and computed tomography showed a mass 10 cm by 10 cm by 8 cm in size with severe calcification in the left quariceps muscle. Occlusion of the left common femoral artery was found in the arteriogram. Surgery was carried out in order to establish an accurate diagnosis and to rescue the left lower limb. The arterial pulsation was recovered as the result of completely resecting the left quariceps muscle tumor. The pathohistological diagnosis was of myositis ossificans in the quariceps muscle of the thigh. Etidronate disodium was administered in order to prevent a recurrence postoperatively. The patient has been well for the 13 months since surgery.


Extracellular proteasome-osteopontin circuit regulates cell migration with implications in multiple sclerosis.
Osteopontin is a pleiotropic cytokine that is involved in several diseases including multiple sclerosis. Secreted osteopontin is cleaved by few known proteases, modulating its pro-inflammatory activities. Here we show by in vitro experiments that secreted osteopontin can be processed by extracellular proteasomes, thereby producing fragments with novel chemotactic activity. Furthermore, osteopontin reduces the release of proteasomes in the extracellular space. The latter phenomenon seems to occur in vivo in multiple sclerosis, where it reflects the remission/relapse alternation. The extracellular proteasome-mediated inflammatory pathway may represent a general mechanism to control inflammation in inflammatory diseases.


BDNF-overexpressing human mesenchymal stem cells mediate increased neuronal protection in vitro.
The use of neurotrophic factors as therapeutic agents for neurodegenerative diseases is considered as an approach aimed at restoring and maintaining neuronal function in the peripheral and central nervous system. Since the neuroprotective effect is depending on chronic delivery of the neurotrophic factors a sustained application, e.g., via cell-based delivery is necessary. Human mesenchymal stem cells (hMSCs) were lentivirally modified to overexpress brain-derived neurotrophic factor (BDNF) and to express fluorescent marker genes for easy visualization. Since genetically modified cells should be site-specifically retained (e.g., by encapsulation) in the patients to avoid adverse effects the cells were additionally differentiated to chondrocytes to hypothetically improve their vitality and survival in a delivery matrix. Different polycations for lentiviral transduction were investigated for their efficiency. The success of differentiation was determined by analysis of chondrocyte marker genes and the neuroprotective effect of BDNF-overexpressing cells was exemplarily investigated on neurons of the peripheral auditory system. The genetically modified hMSCs overexpressed BDNF from under 1 to 125 ng ml-1 day-1 depending on the donor and transfection method. Using protamine sulfate the transfection efficacy was superior compared to the use of polybrene. The BDNF secreted by the MSCs was significantly neuroprotective in comparison to the relevant controls even though the produced mean concentrations were lower than the effective concentrations for recombinant industrially produced proteins described in literature. The presented system of BDNF-overexpressing hMSCs is neuroprotective and is therefore considered as a promising method for sustained delivery of proteins in therapeutically relevant amounts to degenerating neuronal structures.


Particle Swarm Algorithm Path-Planning Method for Mobile Robots Based on Artificial Potential Fields.
Path planning is an important part of the navigation control system of mobile robots since it plays a decisive role in whether mobile robots can realize autonomy and intelligence. The particle swarm algorithm can effectively solve the path-planning problem of a mobile robot, but the traditional particle swarm algorithm has the problems of a too-long path, poor global search ability, and local development ability. Moreover, the existence of obstacles makes the actual environment more complex, thus putting forward more stringent requirements on the environmental adaptation ability, path-planning accuracy, and path-planning efficiency of mobile robots. In this study, an artificial potential field-based particle swarm algorithm (apfrPSO) was proposed. First, the method generates robot planning paths by adjusting the inertia weight parameter and ranking the position vector of particles (rPSO), and second, the artificial potential field method is introduced. Through comparative numerical experiments with other state-of-the-art algorithms, the results show that the algorithm proposed was very competitive.


Horizontal rhythmical eye movements consistently diminish the arousal provoked by auditory stimuli.
Theoretical models implicating the orienting reflex as an explanatory mechanism in the eye-movement desensitization and reprocessing (EMDR) treatment protocol are contrasted and tested empirically. We also test whether EMDR effects are due to a distraction effect. A repeated measure design is used in two experiments. The first experiment employed two independent variables, eye condition (moving vs. stationary) and tone (a pseudo-randomized series of low and high intensity tones). In Expt 2, eye condition was replaced by attentional demand conditions (low or high). In both cases, electrodermal responses served as the dependent variable. Participants were recruited from the Psychology Department at Cardiff University. In Expt 1, participants were required to either pursue a moving stimulus following auditory challenge or engage in an eyes-stationary task. In Expt 2, the task following auditory challenge required participants to identify specific items from letter strings in low and high attentional demand conditions. Lower levels of electrodermal arousal were identified in tasks eliciting eye movements, compared to no eye movements. This effect was not due to the attentional requirements of the task. Eye movements following auditory challenge result in an effect of psychophysiological de-arousal. This supports the reassurance reflex model of EMDR proposed by MacCulloch and Feldman (1996).


Benefits of L-Arginine on Cardiovascular System.
The amino acid, L-Arginine (L-Arg) plays an important role in the cardiovascular system. Data from the literature show that L-Arg is the only substrate for the production of nitric oxide (NO), from which L-Arg develops its effects on the cardiovascular system. As a free radical, NO is synthesized in all mammalian cells by L-Arg with the activity of NO synthase (NOS). In states of hypertension, diabetes, hypercholesterolemia and vascular inflammation a disorder occurs in the metabolic pathway of the synthesis of NO from L-Arg which all together bring alterations of blood vessels. Experimental results obtained on animals, as well as clinical studies show that L-Arg has an effect on thrombocytes, on the process of coagulation and on the fibrolytic system. This mini review represents a summary of the latest scientific animal and human studies related to L-Arg and its mechanisms of actions with a focus on the role of L-Arg via NO pathway in cardiovascular disorders. Moreover, here we present data from recent animal and clinical studies suggesting that L-Arg could be one of the possible therapeutic molecules for improving the treatment of different cardiovascular disorders.


Cost effectiveness of on-line searching of chemical information: an industrial viewpoint.
Cost comparisons and the cost effectiveness of on-line searching of information are reviewed. Topics discussed include on-line vs. manual searching, charge-out of search costs, efficacy of on-line searching, on-line vs. batch computer searching, vendor system comparisons, networking, searcher productivity, telecommunications, role of the intermediary, search transmission rates and on-line charges, editing of recorded searches, and increasing cost of on-line searching of chemical information.


Effect of exercise on sleep quality and insomnia in middle-aged women: A systematic review and meta-analysis of randomized controlled trials.
We assessed the effects of programmed exercise (PE) on sleep quality and insomnia in middle-aged women (MAW). Searches were conducted in five databases from inception through December 15, 2016 for randomized controlled trials (RCTs) evaluating the effects of PE versus a non-exercising control condition on sleep quality, sleep disturbance and/or insomnia in MAW. Interventions had to last at least 8 weeks. Sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI) and insomnia with the Insomnia Severity Index (ISI). Random effects models were used for meta-analyses. The effects on outcomes were expressed as mean differences (MDs) and their 95% confidence intervals (CI). Five publications reported data from four RCTs on PE effects during 12-16 weeks on sleep quality (n=4 studies reporting PSQI results) and/or insomnia (n=3 studies reporting ISI results), including 660 MAW. Low-moderate levels of exercise significantly lowered the PSQI score (MD=-1.34; 95% CI -2.67, 0.00; p=0.05) compared with controls. In a subgroup analysis, moderate PE (aerobic exercise) had a positive effect on sleep quality (PSQI score MD=-1.85; 95% CI -3.62, -0.07; p=0.04), while low levels of physical activity (yoga) did not have a significant effect (MD-0.46, 95% CI -1.79, 0.88, p=0.50). In three studies (two studies of yoga, one study of aerobic exercise), there was a non-significant reduction in the severity of insomnia measured with the ISI score (MD -1.44, 95% CI -3.28, 0. 44, p=0.13) compared with controls. Heterogeneity of effects among studies was moderate to high. In middle-aged women, programmed exercise improved sleep quality but had no significant effect on the severity of insomnia.


Patterning of Lyotropic Chromonic Liquid Crystals by Photoalignment with Photonic Metamasks.
Controlling supramolecular self-assembly in water-based solutions is an important problem of interdisciplinary character that impacts the development of many functional materials and systems. Significant progress in aqueous self-assembly and templating has been demonstrated by using lyotropic chromonic liquid crystals (LCLCs) as these materials show spontaneous orientational order caused by unidirectional stacking of plank-like molecules into elongated aggregates. In this work, it is demonstrated that the alignment direction of chromonic assemblies can be patterned into complex spatially-varying structures with very high micrometer-scale precision. The approach uses photoalignment with light beams that exhibit a spatially-varying direction of light polarization. The state of polarization is imprinted into a layer of photosensitive dye that is protected against dissolution into the LCLC by a liquid crystalline polymer layer. The demonstrated level of control over the spatial orientation of LCLC opens opportunities for engineering materials and devices for optical and biological applications.


Ethylene-promoted intermolecular enyne metathesis.
[reaction: see text] Intermolecular enyne metathesis between functional group-rich alkynes and vinyl ethers was promoted by ethylene cometathesis. The concentration of ethylene was optimized to suppress the competing formation of butadiene through background ethylene metathesis. The role of ethylene appears to be both protective and rate enhancing.


[Solitary ectopic thymoma at ligamentum arteriosum; report of a case].
We report a case of solitary ectopic thymoma at the ligamentum arteriosum, which was resected with thoracoscopic surgery. A 62-year-old male patient received chemoradiation therapy for laryngeal cancer approximately 1 year before. The present computed tomography scan indicated a mass (diameter, 2 cm) at the ligamentum arteriosum. Furthermore, positron emission tomography showed an abnormal accumulation on the mass. Malignant lymphoma and laryngeal cancer with lymph node metastasis were suspected, and thoracoscopic surgery was performed. The tumor had a clear margin;therefore, it could be extirpated easily. The results of the postoperative pathological examination indicated that the tumor was an ectopic thymoma. The patient was discharged 3 days after the surgery because he showed good clinical course and was kept under careful observation.


Use of polymerase chain reaction in an epidemiologic investigation of Pontiac fever.
In June 1992, 13 (38%) of 34 resort guests experienced illness that met a symptom-based case definition of Pontiac fever. Each ill guest reported using an indoor hot tub compared with 6 (29%) of 21 nonill guests (P < .001). Water samples from the indoor hot tub were culture-negative for legionellae using standard techniques, coculture with amebae, and intraperitoneal inoculation of guinea pigs. However, polymerase chain reaction (PCR) testing of the water samples indicated the presence of Legionella pneumophila. Direct fluorescent antibody testing identified the organism as serogroup 6. Seroconversion to L. pneumophila serogroup 6 occurred in 7 (64%) of 11 ill guests and none of 5 nonill guests (P = .03). These results suggest that in certain circumstances, culture of environmental samples should be supplemented with additional tests such as PCR. These results are also consistent with the concept that Pontiac fever can be caused by nonviable legionellae.


Imaged deconvolution: a method for extracting high-resolution NMR spectra from inhomogeneous fields.
We present a novel method for obtaining high resolution NMR spectra in the presence of grossly inhomogeneous magnetic fields, such as those encountered in one-sided access NMR. Our method combines the well-known principle of reference deconvolution with NMR imaging in order to resolve spectral features with frequency resolution orders of magnitude smaller than the prevailing line-broadening due to field inhomogeneity. We demonstrate that, in cases of inhomogeneous field line-broadening more than an order of magnitude larger than the spectral features to be resolved, rather than performing reference deconvolution on the sample as a whole, it is more favourable in terms of SNR to divide the target region of a sample into smaller sub-regions, by means of chemical shift imaging, and then to perform reference deconvolution on the individual sub-region spectra, finally summing the results In this way, significant resolution enhancements can be obtained in the presence of severe magnetic field inhomogeneity without an unacceptable loss in SNR.


Modeling noninvasive neurostimulation in epilepsy as stochastic interference in brain networks.
Noninvasive brain stimulation is one of very few potential therapies for medically refractory epilepsy. However, its efficacy remains suboptimal and its therapeutic value has not been consistently assessed. This is in part due to the nonoptimized spatio-temporal application of stimulation protocols for seizure prevention or arrest, and incomplete knowledge of the neurodynamics of seizure evolution. Through simulations, this study investigated electroencephalography (EEG)-guided, stochastic interference with aberrantly coordinated neuronal networks, to prevent seizure onset or interrupt a propagating partial seizure, and prevent it from spreading to large areas of the brain. Brain stimulation was modeled as additive white or band-limited noise, and simulations using real EEGs and data generated from a network of integrate-and-fire neuronal ensembles were used to quantify spatio-temporal noise effects. It was shown that additive stochastic signals (noise) may destructively interfere with network dynamics and decrease or abolish synchronization associated with progressively coupled networks. Furthermore, stimulation parameters, particularly amplitude and spatio-temporal application, may be optimized based on patient-specific neurodynamics estimated directly from noninvasive EEGs.


Human T-cell leukemia virus type 1 pX-I and pX-II open reading frames are dispensable for the immortalization of primary lymphocytes.
Human T-cell leukemia virus type 1 (HTLV-1) infects and transforms CD4+ T-lymphocytes both in vivo and in vitro. Although the Tax protein of HTLV-1 has been strongly implicated as a transforming agent, other virally encoded proteins may also play a role in the transformation process. In addition to the rex and tax genes, the pX region of the HTLV-1 genome contains two open reading frames (pX-I and pX-II) which encode the putative viral accessory proteins known as p12I, p30II, and p13II. Mutations in the ACH molecular clone of HTLV-1 that are predicted to abrogate the expression of p12I, p13II and p30II were constructed. These mutations had no effect on viral replication or the immortalization of primary lymphocytes. Although these proteins are dispensable for viral replication and immortalization in vitro, it remains possible that they alter infection in vivo.


Tet methylcytosine dioxygenase 1 modulates Porphyromonas gingivalis-triggered pyroptosis by regulating glycolysis in cementoblasts.
Porphyromonas gingivalis is involved in the pathogenesis of multiple polymicrobial biofilm-induced inflammatory diseases, including apical periodontitis, and it triggers pyroptosis accompanied by robust inflammatory responses. Tet methylcytosine dioxygenase 1 (TET1), an epigenetic modifier enzyme, has been is correlated with inflammation, though an association of TET1 and P. gingivalis-related pyroptosis in cementoblasts and the molecular mechanisms has not been shown. Our study here demonstrated that P. gingivalis downregulated Tet1 expression and elicited CASP11- and GSDMD-dependent pyroptosis. Additionally, Tet1 mRNA silencing in cementoblasts appeared to result in a more severe pyroptotic phenotype, where levels of CASP11 and GSDMD cleavage, lactate dehydrogenase release, and IL-1β and IL-18 production were significantly increased. Moreover, Tet1 overexpression resulted in blockade of pyroptosis activation accompanied by inflammation moderation. Further analyses revealed that TET1 modulated glycolysis, confirmed by the application of the specific inhibitor 2-deoxy-d-glucose (2-DG). The pyroptosis phenotype enhanced by Tet1 silencing was moderated by 2-DG upon P. gingivalis invasion. Taken together, these data show the effects and underlying mechanisms of TET1 on pyroptosis and inflammatory phenotype induced by P. gingivalis in cementoblasts, and provides insight into the involvement of P. gingivalis in apical periodontitis and, possibly, other inflammatory diseases.


Mechanism of drug release from double-walled PDLLA(PLGA) microspheres.
The drug release and degradation behavior of two double-walled microsphere formulations consisting of a doxorubicin-loaded poly(d,l-lactic-co-glycolic acid) (PLGA) core (∼46 kDa) surrounded by a poly(d,l-lactic acid) (PDLLA) shell layer (∼55 and 116 kDa) were examined. It was postulated that different molecular weights of the shell layer could modulate the erosion of the outer coating and limit the occurrence of water penetration into the inner drug-loaded core on various time scales, and therefore control the drug release from the microspheres. For both microsphere formulations, the drug release profiles were observed to be similar. The degradation of the microspheres was monitored for a period of about nine weeks and analyzed using scanning electron microscopy, laser scanning confocal microscopy, and gel permeation chromatography. Interestingly, both microsphere formulations exhibited occurrence of bulk erosion of PDLLA on a similar time scale despite different PDLLA molecular weights forming the shell layer. The shell layer of the double-walled microspheres served as an effective diffusion barrier during the initial lag phase period and controlled the release rate of the hydrophilic drug independent of the molecular weight of the shell layer.


Transient appearance of EDTA dependent pseudothrombocytopenia in a patient with 2019 novel coronavirus pneumonia.
EDTA dependent pseudothrombocytopenia (EDTA-PCTP) is a phenomenon that characterized by a spurious decrease of platelets in vitro due to the aggregation of platelets in EDTA anticoagulant blood samples. We report the first case of a transient appearance of EDTA-PCTP in a patient with 2019 novel coronavirus pneumonia (COVID-19). A 59-year-old woman was admitted to the isolated ward for severe type of 2019 novel coronavirus pneumonia. At the time of admission, her platelet count was in a normal range. Two days later, her platelet count decreased gradually without any signs or symptoms of bleeding. Since the peripheral blood smear showed a platelet aggregation, a blood sample anticoagulanted with citrate was tested and the number of platelet was normal. The phenomenon disappeared after 17 days when the patient was cured. This case emphasized the importance of peripheral blood smear and clinical manifestation, especially in the differential diagnosis of thrombocytopenia.


The synthesis of minus-strand RNA of bamboo mosaic potexvirus initiates from multiple sites within the poly(A) tail.
The 3' terminus of the bamboo mosaic potexvirus (BaMV) contains a poly(A) tail, the 5' portion of which participates in the formation of an RNA pseudoknot required for BaMV RNA replication. Recombinant RNA-dependent RNA polymerase (RdRp) of BaMV binds to the pseudoknot poly(A) tail in gel mobility shift assays (C.-Y. Huang, Y.-L. Huang, M. Meng, Y.-H. Hsu, and C.-H. Tsai, J. Virol. 75:2818-2824, 2001). Approximately 20 nucleotides of the poly(A) tail adjacent to the 3' untranslated region (UTR) are protected from diethylpyrocarbonate modification, suggesting that this region may be used to initiate minus-strand RNA synthesis. The 5' terminus of the minus-strand RNA synthesized by the RdRp in vitro was examined using 5' rapid amplification of cDNA ends (RACE) and DNA sequencing. Minus-strand RNA synthesis was found to initiate from several positions within the poly(A) tail, with the highest frequency of initiation being from the 7th to the 10th adenylates counted from the 5'-most adenylate of the poly(A) tail. Sequence analyses of BaMV progeny RNAs recovered from Nicotiana benthamiana protoplasts which were inoculated with mutants containing a mutation at the 1st, 4th, 7th, or 16th position of the poly(A) tail suggested the existence of variable initiation sites, similar to those found in 5' RACE experiments. We deduce that the initiation site for minus-strand RNA synthesis is not fixed at one position but resides opposite one of the 15 adenylates of the poly(A) tail immediately downstream of the 3' UTR of BaMV genomic RNA.


Pseudo-precocious puberty in a young boy due to interstitial cell adenomas of the testis.
A case of pseudo-precocious puberty in a 2 4/12-year-old boy, due to Leydig cell adenomas of the testicle, is described. The special endocrine investigations revealed high levels of plasma testosterone and other androgens together with suppressed plasma gonadotropins unresponsive to stimulation. After operation the hormones returned to normal. The growth velocity and bone age were only gradually decreased, during a period of one year, while the sexual manifestations were the last to disappear, in the third year.


[NIRS-based total quality control system construction of Tanreqing injection and relative thinking].
In this paper, NIRS (near infrared spectroscopy)-based total quality control system for the Tanreqing injection was introduced briefly. By analyzing and summing up the significance and difficulties, several important problems of the practical applications which need urgent solutions are proposed. And also the applicationprospect of NIRS is fully discussed and put forward in the end.


ULTRATHIN SILICON MEMBRANES FOR IMPROVING EXTRACORPOREAL BLOOD THERAPIES.
Extracorporeal blood therapies such as hemodialysis and extracorporeal membrane oxygenation supplement or replace organ function by the exchange of molecules between blood and another fluid across a semi-permeable membrane. Traditionally, these membranes are made of polymers with large surface areas and thicknesses on the scale of microns. Therapeutic gas exchange or toxin cleara nce in these devices occurs predominantly by diffusion, a process that is described by an inverse square law relating a distance to the average time a diffusing particle requires to travel that distance. As such, small changes in membrane thickness or other device dimensions can have significant effects on device performance - and large changes can cause dramatic paradigm shifts. In this work, we discuss the application of ultrathin nanoporous silicon membranes (nanomembranes) with thicknesses on the scale of tens of nanometers to diffusion-mediated medical devices. We discuss the theoretical consequences of nanomembrane medical devices for patients, analyzing several notable benefits such as reduced device size (enabling wearability, for instance) and improved clearance specificity. Special attention is paid to computational and analytical models that describe real experimental behavior, and that in doing so provide insights into the relevant parameters governing the devices.


[Double gallbladders of the Y type. Case report and review of the literature].
The literature is reviewed about double gallbladder. The true double gallbladder is seperated in two gallbladders with two cystic ducts and two cystic arteries. One case is reported with double gallbladder and two cystic ducts coverage to form common channel before they join the common duct (Y shaped type). Both gallbladders and the very large dilated common bile duct contained gallstones. The radiological finding pre-operative was identical with the findings during the operation.


Rh metallene with functionalized polypyrrole surface for hydrogen evolution over a wide pH range.
Interface engineering of two-dimensional (2D) materials by conductive polymer modification is one of the valid methods to promote hydrogen evolution reaction (HER) performance. Herein, we report a simple and universal strategy for the synthesis of polypyrrole (PPy) modified Rh metallene (Rh@PPy metallene) towards an efficient pH-universal HER. Due to the unique ultrathin 2D metallene structure and the optimized electronic structure between the metallene-PPy surfaces, the as-prepared Rh@PPy metallene not only exhibits excellent HER activity with low overpotentials of 16, 39 and 42 mV in 0.5 M H2SO4, 1 M KOH, and 1 M phosphate buffer solution at current density of 10 mA cm-2, but also displays outstanding stability and durability. This work provides a well-founded pathway to constructe metallene-organic interfaces for various electrocatalytic applications.


Sexual abuse victimization and psychological distress among adolescent offenders.
This study focused on sexual abuse victimization and psychological distress among 272 adolescent offenders. The respondents were interviewed while they were being detained in a short-term holding facility. Female respondents reported more sexual abuse victimization and psychological distress than did their male counterparts. Furthermore, church attendance moderated the association between sexual abuse victimization and psychological distress among the male respondents. Implications of these findings for research and interventions with adolescent offenders are discussed.


Legal priorities for prevention of non-communicable diseases: innovations from WHO's Eastern Mediterranean region.
Non-communicable diseases (NCDs) are the leading cause of death globally and in the World Health Organization's (WHO) Eastern Mediterranean region (EMR). This paper reports on a research collaboration between the WHO's Eastern Mediterranean Office (EMRO) and the O'Neill Institute for National and Global Health Law at Georgetown University that aims to identify (1) regionally relevant, cost-effective and affordable legal interventions to prevent NCDs, and (2) methods to strengthen implementation and enforcement. Comparative analysis of >200 international, regional and domestic interventions addressing key NCD risk factors, including tobacco, alcohol, diet and physical inactivity. Researchers searched legal and policy databases including the WHO Nutrition, Obesity and Physical Activity Database and drew upon academic commentary and 'grey' literature. Measures included evidence of impact; evidence of cost-effectiveness; and monitoring and enforcement mechanisms. Researchers identified many examples of legal interventions effectively reducing NCD risk factors. Key enabling factors for effective NCD-related laws include regulatory capacity; governance mechanisms promoting multisectoral collaboration and accountability; and tailoring interventions to local legal, economic and social contexts. In the EMR, and globally, law can be a cost-effective and affordable means of curbing underlying drivers of the NCD pandemic, such as rampant junk food marketing. Building upon this research, together with international and regional experts, EMRO has identified 10 priority interventions in the areas of tobacco control, unhealthy diets and NCD governance. The EMRO/O'Neill Institute partnership will develop guidance tools and capacity building initiatives to support Member States to harness the power of law to achieve population health improvements.


Robust Prognostic Subtyping of Muscle-Invasive Bladder Cancer Revealed by Deep Learning-Based Multi-Omics Data Integration.
Muscle-invasive bladder cancer (MIBC) is the most common urinary system carcinoma associated with poor outcomes. It is necessary to develop a robust classification system for prognostic prediction of MIBC. Recently, increasing omics data at different levels of MIBC were produced, but few integration methods were used to classify MIBC that reflects the patient's prognosis. In this study, we constructed an autoencoder based deep learning framework to integrate multi-omics data of MIBC and clustered samples into two different subgroups with significant overall survival difference (P = 8.11 × 10-5). As an independent prognostic factor relative to clinical information, these two subtypes have some significant genomic differences. Remarkably, the subtype of poor prognosis had significant higher frequency of chromosome 3p deletion. Immune decomposition analysis results showed that these two MIBC subtypes had different immune components including macrophages M1, resting NK cells, regulatory T cells, plasma cells, and naïve B cells. Hallmark gene set enrichment analysis was performed to investigate the functional character difference between these two MIBC subtypes, which revealed that activated IL-6/JAK/STAT3 signaling, interferon-alpha response, reactive oxygen species pathway, and unfolded protein response were significantly enriched in upregulated genes of high-risk subtype. We constructed MIBC subtyping models based on multi-omics data and single omics data, respectively, and internal and external validation datasets showed the robustness of the prediction model as well as its ability of prognosis (P < 0.05 in all datasets). Finally, through bioinformatics analysis and immunohistochemistry experiments, we found that KRT7 can be used as a biomarker reflecting MIBC risk.


Griffith Pugh, pioneer Everest physiologist.
Lewis Griffith Cresswell Evans Pugh (1909-1994), best known as the physiologist on the successful 1953 British Everest Expedition, inspired a generation of scientists in the field of altitude medicine and physiology in the decades after World War II. This paper details his early life, his introduction to exercise physiology during the war, and his crucially important work in preparation for the Everest expedition on Cho Oyu in 1952. Pugh's other great contribution to altitude physiology was as scientific leader of the 1960-1961 Himalayan Scientific and Mountaineering Expedition (the Silver Hut), and the origins and results of this important expedition are discussed. He had a major and continuing interest in the physiology of cold, especially in real-life situations in Antarctica, exposure to cold wet conditions on hills in Britain, and in long distance swimming. He also extended his interest to Olympic athletes at moderate altitude (Mexico City) and to heat stress in athletes. Pugh's strength as a physiologist was his readiness to move from laboratory to fieldwork with ease and his rigor in applying the highest standards in both situations. He led by example in both his willingness to act as a subject for experiments and in his attention to detail. He was not an establishment figure; he was critical of authority and well known for his eccentricity, but he inspired great loyalty in those who worked with him.


Anatomic and sonographic features of the fetal skull.
This article reviews developmental skull anatomy, especially as it relates to the formation of cranial sutures and fontanelles, and demonstrates the appearance of these structures on prenatal sonograms, illustrating the framework these structures provide to enable one to accurately identify components of the fetal skull. Examples are provided to illustrate the utility of this knowledge. An understanding of fetal skull development and appearance enables the sonographer to better characterize fetal cranial abnormalities. More importantly, recognition of the location of cranial sutures and fontanelles and their ability to serve as acoustic windows assists the sonographer in evaluation of the fetal brain.


Isolation and structural elucidation of antiproliferative compounds of lipidic fractions from white shrimp muscle (Litopenaeus vannamei).
Shrimp is one of the most popular seafood items worldwide, and has been reported as a source of chemopreventive compounds. In this study, shrimp lipids were separated by solvent partition and further fractionated by semi-preparative RP-HPLC and finally by open column chromatography in order to obtain isolated antiproliferative compounds. Antiproliferative activity was assessed by inhibition of M12.C3.F6 murine cell growth using the MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide) assay. The methanolic fraction showed the highest antiproliferative activity; this fraction was separated into 15 different sub-fractions (M1-M15). Fractions M8, M9, M10, M12, and M13 were antiproliferative at 100 µg/mL and they were further tested at lower concentrations. Fractions M12 and M13 exerted the highest growth inhibition with an IC50 of 19.5 ± 8.6 and 34.9 ± 7.3 µg/mL, respectively. Fraction M12 was further fractionated in three sub-fractions M12a, M12b, and M12c. Fraction M12a was identified as di-ethyl-hexyl-phthalate, fraction M12b as a triglyceride substituted by at least two fatty acids (predominantly oleic acid accompanied with eicosapentaenoic acid) and fraction M12c as another triglyceride substituted with eicosapentaenoic acid and saturated fatty acids. Bioactive triglyceride contained in M12c exerted the highest antiproliferative activity with an IC50 of 11.33 ± 5.6 µg/mL. Biological activity in shrimp had been previously attributed to astaxanthin; this study demonstrated that polyunsaturated fatty acids are the main compounds responsible for antiproliferative activity.


Impaired glucose tolerance and diabetes mellitus in elderly subjects.
In a 10-yr prospective population study 406 subjects who were 70 yr old received an oral glucose tolerance test. Of these subjects 169 were retested at 80. Three sets of diagnostic criteria were evaluated, of which the WHO criteria are recommended for screening studies in this age group. The prevalences of diabetes mellitus (DM) and impaired glucose tolerance (IGT) according to the latter criteria were 10% and 26% at 70 and 12% and 35% at 80 in men and women. Excess 10-yr mortality was seen in both sexes when DM existed at 70, and in men also when IGT existed at this age. The excess mortality in men could solely--and in women partly--be explained by cardiovascular diseases. The 10-yr incidence of DM was 20% if IGT existed at 70, but only 4% when normal glucose tolerance was present at 70.


P019 Not All Fecal Calprotectin is Specific for Inflammatory Bowel Disease.
Introduction:Fecal calprotectin is a known inflammatory marker used to evaluate patients with Inflammatory Bowel Disease (IBD). In fact, ACG Clinical Guideline for management of Crohn's disease recommend fecal calprotectin (FC) as a helpful test to distinguish IBD versus functional disorder such as Irritable Bowel Syndrome. Studies have also shown association of fecal calprotectin with colon cancer. Recent study proposed fecal calprotectin could be a reliable marker for ruling out organic disease with high negative predictive value. We present a patient case of a Caucasian, thirty-five years of age male with PMHx of GERD on Prilosec who presented due to acute abdominal pain, nausea, emesis and watery, nonbloody diarrhea of four days duration. Initially, patient had unknown family history of colon cancer which later was revealed that patient's father had a colon cancer diagnosis in his fifties. On admission, patient had stable vitals with routine labs showing leukocytosis, iron deficiency anemia, normal CRP, and elevated fecal calprotectin of 986mcg/gm. Abdominal imaging with CT abdomen with contrast showed diffuse dilation of ileum and thickening of the distal ileum up to the level of the ileocecal junction, suggestive of enteritis from infectious or inflammatory etiology such as Crohn's. Patient was managed conservatively, stool studies were negative otherwise and discharged with outpatient endoscopy due to high suspicion for Inflammatory Bowel Disease. Within one week, patient had a subsequent readmission for now partial small bowel obstruction at the level of ileum. Due to high suspicion of Crohn's, patient was empirically started on IV steroids. Decision for inpatient colonoscopy was made with colonoscopy showing completely obstructing, circumferential, large mass found in the cecum extending into ascending colon. Final pathology revealed invasive mucinous adenocarcinoma, moderately differentiated. Patient subsequently underwent right hemicolectomy with lymph node resection and adjuvant chemotherapy treatment for stage 3 colon. We present here a case where a common cancer was found in an otherwise healthy, young male with acute abdominal pain and altered bowel habits. While initial symptoms, imaging and laboratory findings pointed towards a biased high suspicion for Inflammatory Bowel Disease, patient's ultimate diagnosis was stage 3 adenocarcinoma of colon requiring surgical resection and chemotherapy. Fecal calprotectin is a known marker for colon inflammation and associated with both IBD and colon cancer. It is important to keep in mind that while fecal calprotectin may have elevated negative predictive value and be used to rule out organic disease, elevation of fecal calprotectin is not always specific for IBD. We want to emphasize the importance of considering colon cancer on the differential despite a patient's age and diagnostic bias. Lastly, we also want to highlight the importance of tissue diagnosis prior to long term therapy use.


First case of visceral leishmaniasis caused by Leishmania martiniquensis.
We report the first case of visceral leishmaniasis (VL) caused by Leishmania martiniquensis in the Caribbean, which until now, was known only to cause cutaneous leishmaniasis. The disease presented with fatigue, anemia, and hepatosplenomegaly in a 61-year-old man with human immunodeficiency virus (HIV) infection who was receiving antiretroviral therapy. Diagnosis was made by bone marrow biopsy. VL is life-threatening, and its emergence in the Caribbean is of concern.


Synthesis, characterization and biological evaluation of functionalized polystyrene particles.
In this paper we synthesized a series of carboxylate and amino functionalized polystyrene nanoparticles with controllable size and surface properties by conventional and seed emulsion polymerization methods. They are characterized by dynamic light scattering (DLS) and transmission electron microscope (TEM). Additionally the content of carboxylate and amino groups on the surface of the particles are determined accurately by conductometric titration and fluorescamine technique respectively. Afterwards the toxicity of amino modified polystyrene particles was tested in 1321N1 astrocytoman cell line and the results showed the degree of the toxicity is proportional to the amino content of the particles, suggesting the amino group is responsible for the toxicity of the particles. Furthermore those particles were labeled by fluorescent dye and confocal fluorescent microscopy experiment showed that the particles can be well absorbed by cells.


Intravenous immunoglobulin as adjunct therapy for refractory pyoderma gangrenosum: systematic review of cases and case series.
Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis. Treatment regimens for refractory cases are nonstandardized. Intravenous immunoglobulin (IVIG) is an emerging treatment with reported success, but the efficacy of IVIG for PG is unknown. In this systematic review of cases and case series, we assessed the efficacy of IVIG for the treatment of PG, as observed at our institution and reported in the literature. A retrospective chart review at two tertiary care hospitals between 2000 and 2015, and literature searches in PubMed/MEDLINE, EMBASE and Web of Science from all years were conducted. In total, there were 49 patients, including 43 patients from 26 articles and six institutional cases. There was complete or partial response in 43 (88%) patients and complete response in 26 (53%) patients. The mean time to initial response to treatment and treatment length were 3·5 (SD 3·3) weeks and 5·9 (SD 7·8) months, respectively. On average, 2·6 treatments had been trialled before IVIG initiation. IVIG was administered with systemic steroids in 43 (88%) cases. Mild adverse events, especially nausea and headache, were reported in 12 (24·5%) patients. Our systematic review suggests a potential role for IVIG as adjuvant therapy for refractory PG. Prospective clinical trials testing the efficacy of IVIG for refractory PG are needed to validate these findings.


Synthesis of Benzopyridoindolone Derivatives via a One-Pot Copper Catalyzed Tandem Reaction of 2-Iodobenzamide Derivatives and 2-Iodobenzylcyanides.
An efficient approach for the synthesis of benzo-fused pyridoindolone derivatives via a one-pot copper catalyzed tandem reaction of 2-iodobenzamides with 2-iodobenzylcyanides has been developed. Using this protocol, benzo-fused pyridoindolone derivatives are obtained in high yields in a relatively short period of time under mild reaction conditions. To the best of our knowledge, this is the first approach where one can synthesize free indole N-H benzo-fused pyridoindolones. Also, both indole and pyridone cores are constructed during the course of the reaction. The methodology shows good functional group tolerance and allows synthesis of thiophene-fused pyridoindolones and fused indolobenzonaphthyridone derivatives.


Protein-Based Multifunctional Nanocarriers for Imaging, Photothermal Therapy, and Anticancer Drug Delivery.
We report a simple approach for fabricating plasmonic and magneto-luminescent multifunctional nanocarriers (MFNCs) by assembling gold nanorods, iron oxide nanoparticles, and gold nanoclusters within BSA nanoparticles. The MFNCs showed self-tracking capability through single- and two-photon imaging, and the potential for magnetic targeting in vitro. Appreciable T2-relaxivity exhibited by the MFNCs indicated favorable conditions for magnetic resonance imaging. In addition to successful plasmonic-photothermal therapy of cancer cells (HeLa) in vitro, the MFNCs demonstrated efficient loading and delivery of doxorubicin to HeLa cells leading to significant cell death. The present MFNCs with their multimodal imaging and therapeutic capabilities could be eminent candidates for cancer theranostics.


pH-Responsive Nanoscale Coordination Polymer for Efficient Drug Delivery and Real-Time Release Monitoring.
Both excess dosages of drug and unwanted drug carrier can lead to severe side effects as well as the failure of tumor therapy. Here, an Fe3+ -gallic acid based drug delivery system is designed for efficient monitoring of drug release in tumor. Fe3+ and polyphenol gallic acid can form polygonal nanoscale coordination polymer in aqueous solution, which exhibits certain antitumor effect. Importantly, this coordination polymer possesses extremely high doxorubicin (DOX) loading efficacy (up to 48.3%). In vitro studies demonstrate that the fluorescence of DOX can be quenched efficiently when DOX is loaded on the coordination polymer. The acidity in lysosome also triggers the release of DOX and fluorescence recovery simultaneously, which realizes real-time monitoring of drug release in tumor cells. In vivo studies further indicate that this polyphenol-rich drug delivery system can significantly inhibit tumor growth with negligible heart toxicity of DOX. This system with minimal side effects should be a promising nanoplatform for tumor treatment.


NetCmpt: a network-based tool for calculating the metabolic competition between bacterial species.
NetCmpt is a tool for calculating the competitive potential between pairs of bacterial species. The score describes the effective metabolic overlap (EMO) between two species, derived from analyzing the topology of the corresponding metabolic models. NetCmpt is based on the EMO algorithm, developed and validated in previous studies. It takes as input lists of species-specific enzymatic reactions (EC numbers) and generates a matrix of the potential competition scores between all pairwise combinations. NetCmpt is provided as both a web tool and a software package, designed for the use of non-computational biologists. The NetCmpt web tool, software, examples, and documentation are freely available online at http://app.agri.gov.il/shiri/NetComp.php.


Effects of lipooligosaccharide inner core truncation on bile resistance and chick colonization by Campylobacter jejuni.
Campylobacter jejuni is the most common bacterium that causes diarrhea worldwide, and chickens are considered the main reservoir of this pathogen. This study investigated the effects of serial truncation of lipooligosaccharide (LOS), a major component of the outer membrane of C. jejuni, on its bile resistance and intestinal colonization ability in chickens. Genes encoding manno-heptose synthetases or glycosyltransferases were inactivated to generate isogenic mutants. Serial truncation of the LOS core oligosaccharide caused a stepwise increase in susceptibilities of two C. jejuni strains, NCTC 11168 and 81-176, to bile acids. Inactivation of hldE, hldD, or waaC caused severe truncation of the core oligosaccharide, which greatly increased the susceptibility to bile acids. Both wild-type strains grew normally in chicken intestinal extracts, whereas the mutants with severe oligosaccharide truncation were not detected 12 h after inoculation. These mutants attained viable bacterial counts in the bile acid-free extracts 24 h after inoculation. The wild-type strain 11-164 was present in the cecal contents at >10(7) CFU/g on 5 days after challenge infection and after this time period, whereas its hldD mutant was present at <10(3) CFU/g throughout the experimental period. Trans-complementation of the hldD mutant with the wild-type hldD allele completely restored the in vivo colonization level to that of the wild-type strain. Mutants with a shorter LOS had higher hydrophobicities. Thus, the length of the LOS core oligosaccharide affected the surface hydrophobicity and bile resistance of C. jejuni as well as its ability to colonize chicken intestines.


[Immunochemical and biochemical characteristics of a preventive preparation against cholera, cholerogen-toxoid].
Cholerogen-toxoid served as a complex vaccine preparation composed of the main pathogenicity factors of cholera vibrio--cholerogen (toxoid), endotoxin and a number of exoenzymes. The preparation contains 65 +/- 7.5% of protein, 12 +/- 1.2% of reducing sugars, 7 +/- 1.2% of lipids, and 2 +/- 0.3% of nucleic acids. Analytic disc-electrophoresis in polyacrylamide gel and immune disc-electrophoresis revealed at least seven individual proteins with the serological activity in the preparation. About 70% of these constituted toxoid proper; the content of O-antigen was 22%. In the cholerogen-toxoid there were revealed seven exoenzymes of cholera vibrio; proteinase, lecithinase, lipase, DNA-ase, RNA-ase, hyaluronidase, amylase. Antibodies against proteinase, lecithinase, amylase and RNA-ase of cholera vibrio were found in the serum of rabbits immunized with cholerogen-toxoid.


Evaluation of Cerebrovascular Events Followed in Pediatric Intensive Care Unit.
To evaluate the effect of intensive care follow-up and treatment methods on the prognosis of 28 patients admitted to the pediatric intensive care unit (PICU) due to stroke. The data of patients aged between 28 days and 18 years followed up between 2011 and 2021 were recorded retrospectively. Thirteen (48.1%) patients were diagnosed with hemorrhagic stroke (HS), 11 (40.7%) patients were diagnosed with acute ischemic stroke (AIS), and three (11.1%) patients were diagnosed with cerebral sinus vein thrombosis. One patient was followed up for non-ruptured arteriovenous malformation (AVM) and was excluded from the HS group. The HS group consisted of eight patients with ruptured AVMs and five patients with ruptured intracranial aneurysms. The patients had male predominance, and seizures and headache were the most common complaints on admission. The rate of admissions due to seizures was higher in the AIS group. In the HS group, there was more involvement of the right side of the brain. Middle cerebral artery (MCA) involvement was higher in the AIS group. The AIS group had longer PICU hospitalization days and mechanical ventilator days. While unfractionated heparin was preferred for the treatment in the AIS group, endovascular embolization was preferred in the HS group. Decompressive surgery was performed in five patients. The overall mortality rate was 7.1%. Although cerebrovascular events are rare in the pediatric population, achieving low mortality and morbidity is possible with the correct diagnostic and treatment methods.


Preoperative screening and prehabilitation strategies prior to ileocolic resection in patients with Crohn's disease are not incorporated in routine care.
Recently, recommendations on perioperative care have been published to optimize postoperative outcomes in preoperative patients with inflammatory bowel disease. This study evaluated the current use of preoperative screening and prehabilitation strategies (PS) prior to elective ileocolic resection (ICR) in patients with Crohn's disease (CD). Patients with CD who underwent an elective ICR were identified from a Dutch prospective cohort study. Primary endpoint was to evaluate to what extent IBD-relevant PS were applied in patients with CD prior to ICR according to the current recommendations. In total, 109 CD patients were included. Screening of nutritional status was performed in 56% of the patients and revealed malnutrition in 46% of these patients. Of the malnourished patients, 46% was referred to a dietitian. Active smoking and alcohol consumption were reported in 20% and 28%; none of these patients were referred for a cessation program. A preoperative anemia was diagnosed in 61%, and ferritin levels were assessed in 26% of these patients. Iron therapy was started in 25% of the patients with an iron deficiency anemia. Exposure to corticosteroids at time of ICR was reported in 29% and weaned off in 3%. Consultation of a dietitian, psychologist, and physiotherapist was reported in 36%, 7%, and 3%. Physical fitness was assessed in none of the patients. PS are not routinely applied and not individually tailored in the preoperative setting prior to elective ICR in patients with CD. Prior to implementation, future research on the costs and effectiveness of PS on postoperative outcomes and quality of life is necessary.


Reactivity of T cells in mycosis fungoides exhibiting marked epidermotropism with the monoclonal antibody HML-1 that defines a membrane molecule on human mucosal lymphocytes.
Twenty-eight cases of cutaneous T cell lymphomas of mycosis fungoides type, 8 of which showed a marked epidermotropism, were investigated for their reactivity with the monoclonal antibody HML-1. This reagent selectively recognizes human benign and malignant intestinal T lymphocytes, but not benign or malignant lymph node T cells. In all cases, the majority of nonepithelium-associated T cells present in the corium were HML-1 negative. In the eight cases with marked epidermotropism, the intraepidermal (IED) T cells were HML-1 positive in three cases, and HML-1 negative in the remaining five cases. The HML-1 positive IED T cells tended to be localized preferentially in the basal layers, whereas the HML-1 negative IED T cells were more diffusely distributed throughout all epidermal cell layers or formed intra-epidermal aggregates. These findings provide further evidence that mycosis fungoides is not a single entity, but represents a group of neoplasms originating from different T cell subsets that have in common their tropism to epidermis and/or dermis, and thus have a similar clinical presentation.


Sequential treatment strategy for malignant pleural effusion in non-small cell lung cancer with the activated epithelial grow factor receptor mutation.
With the advent of molecularly targeted therapy, it is necessary to reconsider the strategy for malignant pleural effusion in non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations. The aim of this study was to evaluate the efficacy of a two-line sequential treatment strategy in this patient subgroup. First-line treatment was gefitinib (250 mg/day) until disease progression. Second-line treatment was thoracoscopic talc pleurodesis followed by chemotherapy. Primary endpoints were the overall response and progression-free survival rates after first-line treatment, and the overall survival rate after first- and second-line treatment. Secondary endpoints were the success rate of thoracoscopic talc pleurodesis and gefitinib toxicity. Among the 76 patients enrolled, 61 (80%) were female and the median age was 62 years. The overall response rate after first-line treatment was 92.1% and median progression-free survival was 15 months. The success rate for thoracoscopic talc pleurodesis in 33 patients was 94%. Median follow-up was 35 months. Median overall survival was 39 months. The 1- and 3-year overall survival rates were 86.4% and 46.1%, respectively. The two-line sequential treatment strategy enhanced survival. These preliminary findings provide an insight into novel therapeutic models for malignant pleural effusion in NSCLC harbouring EGFR mutations.


Bladder activation: afferent mechanisms.
The major function of the lower urinary tract is to store and periodically evacuate urine from the bladder. This requires coordination of the smooth muscles of the bladder and urethra, and of the striated muscles of the outflow region and pelvic floor by a complex neural control system. Lumbosacral afferent fibers (pelvic afferents), but also afferents in the hypogastric and pudendal nerves, are of major importance for the regulation of the mechanisms for continence and micturition. In the bladder, afferent nerves have been identified suburothelially as well as in the detrusor muscle. Suburothelially, they form a plexus that lies immediately beneath the epithelial lining. This plexus is particularly dense in the bladder neck and the trigone. The most important afferents for the micturition process are myelinated Adelta-fibers and unmyelinated C-fibers. Immunocytochemical and tracing studies have revealed that numerous peptides, including substance P, calcitonin gene-related peptide, vasoactive intestinal polypeptide, enkephalins, and cholecystokinin are localized either alone, or in combination, in afferent pathways of the bladder and urethra. The receptors on these nerves include: vanilloid receptors, purinoceptors, tachykinin, and prostanoid receptors. Extracellular adenosine triphosphate (ATP) has been found to mediate excitation of small-diameter sensory neurons via P2X3 receptors, and it has been proposed that in the bladder, distention causes release of ATP from the urothelium. ATP, in turn, can activate P2X3 receptors on suburothelial afferent nerve terminals to evoke a neural discharge. However, it is most likely that a cascade of inhibitory and stimulatory transmitters/mediators, as well as ATP, are involved in the transduction mechanisms underlying the activation of afferent fibers during bladder filling.


High velocity dispersion in a rare grand-design spiral galaxy at redshift z = 2.18.
Although grand-design spiral galaxies are relatively common in the local Universe, only one has been spectroscopically confirmed to lie at redshift z > 2 (HDFX 28; z = 2.011); and it may prove to be a major merger that simply resembles a spiral in projection. The rarity of spirals has been explained as a result of disks being dynamically 'hot' at z > 2 (refs 2-5), which may instead favour the formation of commonly observed clumpy structures. Alternatively, current instrumentation may simply not be sensitive enough to detect spiral structures comparable to those in the modern Universe. At z < 2, the velocity dispersion of disks decreases, and spiral galaxies are more numerous by z ≈ 1 (refs 7, 13-15). Here we report observations of the grand-design spiral galaxy Q2343-BX442 at z = 2.18. Spectroscopy of ionized gas shows that the disk is dynamically hot, implying an uncertain origin for the spiral structure. The kinematics of the galaxy are consistent with a thick disk undergoing a minor merger, which can drive the formation of short-lived spiral structure. A duty cycle of <100 Myr for such tidally induced spiral structure in a hot massive disk is consistent with its rarity.


Transmitral resection of left ventricular lipoma by right mini-thoracotomy using a rolled up flexible ruler.
Left ventricular lipoma is a rare intracardiac tumour that is usually resected through sternotomy to effectively explore the left ventricular cavity. We introduce a simple technique to expose the left ventricular cavity and resect the intraventricular lipoma using a rolled up flexible ruler through right mini-thoracotomy. Imaging studies and gross and microscopic photography of intraventricular lipoma are presented in this report.


Bilateral nephrectomy of huge polycystic kidneys associated with a rectus abdominis diastasis and umbilical hernia.
Patients with end-stage renal failure due to huge autosomal dominant polycystic kidney disease usually have an umbilical hernia and rectus abdominis diastasis, which are very troublesome. Pretransplant bilateral nephrectomy techniques does not manage the umbilical hernia and rectus abdominis diastasis. We report our experience in performing bilateral nephrectomy and repairing the rectus abdominis diastasis and umbilical hernia through the one, small incision. Four patients aged 37 to 43 years with huge polycystic kidneys, an umbilical hernia, and a rectus abdominis diastasis underwent bilateral pretransplant nephrectomy through a midline supraumbilical incision including the umbilical hernia defect. The kidneys were removed through this incision. The incision was closed with the transposition of rectus abdominis muscle, pants-over-vest-style, to correct the diastasis and the umbilical hernia. The average operative time was 160 minutes (range, 130-180); the average larger kidney size was 33 cm (range, 32-34 cm); no major complications occurred; one patient who had preoperative low hemoglobin required blood transfusion. Patients were discharged from the hospital on postoperative day 7 with an esthetically pleasing belly, no rectus abdominis diastasis, and no umbilical hernia. One to two months after bilateral nephrectomy, the patients received a live donor kidney with an uneventful outcome. A midline supraumbilical incision is an excellent approach for bilateral nephrectomy of huge polycystic kidneys. In addition, an umbilical hernia and rectus abdominis diastasis may be successfully repaired through same incision with good cosmetic results.


The variability of orocecal transit time evaluated by the salicylazosulphapyridine/sulphapyridine method.
The inter- and intrasubject variability of the orocecal transit time assessed by the salicylazosulphapyridine/sulphapyridine test was examined. Nine healthy males attended on 3 occasions. Between-days comparison gives highly reproducible transit times for the subjects considered as a group (median values and their 95%-confidence limits): 4.0 (3.5-4.5), 4.5 (3.5-5.0), and 4.5 (3.0-4.5) hours, respectively. Fifty-nine per cent of the individual transit times amounts to 4.0 or 4.5 hours. Within subject comparison revealed marked differences for 4 of the volunteers. The maximum between-days differences observed were 1.0 (3 subjects) and 2.5 hours, respectively. Similar results of variability become evident regarding the area under the sulphapyridine concentration-time curves. In conclusion, it appears reasonable to use this method in assessing e.g. the effects of drugs on the transit time in crossover studies.


Structural basis of template-boundary definition in Tetrahymena telomerase.
Telomerase is required to maintain repetitive G-rich telomeric DNA sequences at chromosome ends. To do so, the telomerase reverse transcriptase (TERT) subunit reiteratively uses a small region of the integral telomerase RNA (TER) as a template. An essential feature of telomerase catalysis is the strict definition of the template boundary to determine the precise TER nucleotides to be reverse transcribed by TERT. We report the 3-Å crystal structure of the Tetrahymena TERT RNA-binding domain (tTRBD) bound to the template boundary element (TBE) of TER. tTRBD is wedged into the base of the TBE RNA stem-loop, and each of the flanking RNA strands wraps around opposite sides of the protein domain. The structure illustrates how the tTRBD establishes the template boundary by positioning the TBE at the correct distance from the TERT active site to prohibit copying of nontemplate nucleotides.


Multivariate analysis to discriminate species of phlebotomine sand flies (Diptera:Psychodidae): Lutzomyia townsendi, L. spinicrassa, and L. youngi.
Multivariate discriminant analysis was employed to discriminate on a morphological basis females of 3 closely related sand fly species, Lutzomyia townsendi (Ortiz), L. spinicrassa Morales, Osorno-Mesa, Osorno & Hoyos, and L. youngi Feliciangeli & Murillo. Principal component and canonical discriminant analysis compared a set of 31 morphological characters measured from known specimens to detect differences among the 3 species. A subset of 6 characters separated the 3 species with a high level of confidence. A simple method is presented to identify an unknown specimen as L. townsendi, L. spinicrassa, or L. youngi using these 6 morphological characters.


High prolactin and low dehydroepiandrosterone sulphate serum levels in patients with severe systemic sclerosis.
The aim was to determine serum levels of prolactin (PRL) and dehydroepiandrosterone sulphate (DHEAS), and to demonstrate a link between PRL or DHEAS and soluble immune mediators in patients with systemic sclerosis (SSc) with different degrees of disease-induced organ involvement. Thirty-one patients with SSc were studied to evaluate 18 possible disease manifestations. In the serum, PRL, DHEAS and soluble immune mediators were determined by ELISA. Compared to SSc with <9 disease manifestations, patients with > or =9 disease manifestations had higher PRL (P = 0.044), higher soluble interleukin 2 receptor (sIL-2R, P = 0.004) and vascular cell adhesion molecule (sVCAM, P = 0.044), and lower DHEAS (P = 0.029). PRL (R(Rank) = 0.490, P = 0.003) and DHEAS (R(Rank) = -0.399, P = 0.013) were significantly correlated with the number of disease manifestations. The inverse correlation between PRL and DHEAS showed a trend (P = 0.059). PRL correlated with sIL-2R (R(Rank) = 0.553, P = 0.001) and sVCAM (R(Rank) = 0.520, P = 0.002). The number of disease manifestations and sIL-2R correlated significantly (R(Rank) = 0.463, P = 0.006). Psychometric variables to examine the presence of depression were not measured, but from the general aspect, the patients were not suffering from major depression which may have influenced our results. In conclusion, this study demonstrates the close association between DHEAS and, particularly, PRL and SSc severity and T-lymphocyte mechanisms.


Genetic and molecular control of folate-homocysteine metabolism in mutant mice.
Hyperhomocysteinemia adversely affects fundamental aspects of fetal development, adulthood, and aging, but the role of elevated homocysteine levels in these birth defects and adult diseases remains unclear. Mouse models are valuable for investigating the causes and consequences of hyperhomocysteinemia. We used a phenotype-based approach to identify mouse mutants for studying the relation between single gene mutations, homocysteine levels as a measure of the status of homocysteine metabolism, and gene expression profiles as a way to assess the impact of protein deficiency in mutant mice on steady-state transcription levels of genes in the folate-homocysteine pathways. These mutants were selected based on their propensity to produce phenotypes that are reminiscent of those associated with anomalies in folate-homocysteine metabolism in humans. We report identification of new, single-gene mouse models of homocysteinemia and characterization of their molecular and physiological impact on folate-homocysteine metabolism. Mutations in several genes involved in the hedgehog and WNT signal transduction pathways, as well as a gene involved in lipid metabolism, resulted in elevated homocysteine levels and altered expression profiles of folate-homocysteine metabolism genes. These results begin to unravel the complex relations between elevation of a single amino acid in the blood and the diverse birth defects and adult diseases associated with hyperhomocysteinemia.


Alzheimer amyloid beta-peptide inhibits the late phase of long-term potentiation through calcineurin-dependent mechanisms in the hippocampal dentate gyrus.
The perforant path projecting from the entorhinal cortex to the hippocampal dentate gyrus is a particularly vulnerable target to the early deposition of amyloid beta (Abeta) peptides in Alzheimer's brain. The authors previously showed that brief applications of Abeta at subneurotoxic concentrations suppressed the early-phase long-term potentiation (E-LTP) in rat dentate gyrus. The current study further examines the effect of Abeta on the late-phase LTP (L-LTP) in this area. Using multiple high-frequency stimulus trains, a stable L-LTP lasting for at least 3 h was induced in the medial perforant path of rat hippocampal slices. Bath application of Abeta(1-42) (0.2-1.0 microM) during the induction trains attenuated both the initial and late stages of L-LTP. On the other hand, Abeta(1-42) perfusion within the first hour following the induction primarily impaired the late stage of L-LTP, which resembled the action of the protein synthesis inhibitor emetine. Blockade of calcineurin activity with FK506 or cyclosporin A completely prevented Abeta-induced L-LTP deficits. These results suggest that Abeta(1-42) impaired both the induction and maintenance phase of dentate L-LTP through calcineurin-dependent mechanisms. In the concentration range effective for inhibiting L-LTP, Abeta(1-42) also reduced the amplitude of NMDA receptor-mediated synaptic currents in dentate granule cells via a postsynaptic mechanism. In addition, concurrent applications of Abeta(1-42) with the protein synthesis inhibitor caused no additive reduction of L-LTP, indicating a common mechanism underlying the action of both. Thus, inhibition of NMDA receptor channels and disruption of protein synthesis were two possible mechanisms contributing to Abeta-induced L-LTP impairment.


Analyzing alertness among people with profound multiple disabilities: implications for provision of training.
We investigated whether variations in alertness among individuals with profound multiple disabilities affected subsequent responsiveness to training programs. Three experiments were conducted involving 5 people. In Experiment 1, results indicated that alertness of 3 individuals increased with provision of skill-acquisition training programs. Results also indicated no predictive relationship between alertness levels prior to training and subsequent responsiveness to training. Experiment 2 replicated results of Experiment 1 with 2 participants from Experiment 1 and an additional participant. Results of Experiment 2 also indicated that the increased alertness levels accompanying provision of training were not a function of the participants simply being in an inactive environment prior to training. Results of Experiment 3 indicated that alertness of an additional participant increased through provision of another training intervention, involving a systematic preference assessment. Responses during the preference assessment appeared to be unrelated to previously existing alertness levels. These findings suggest the need for caution when considering the withholding of scheduled training because an individual appears to be nonalert.


Periprosthetic Shoulder Infection management: one-stage should be the way - A systematic review and meta-analysis.
There is still no consensus among surgeons on whether to perform a one or two-stage surgical revision in infected shoulder arthroplasties. The aim of this systematic review and meta-analysis is to rigorously synthesize published studies evaluating the clinical outcomes, recurrence of infection and other clinical complications, in order to discuss which is the best strategy for treating periprosthetic joint infection (PJI) after shoulder arthroplasty. Upon research using PubMed, SCOPUS and Web of Science databases, on November 2022, studies which presented one or two-stage surgical revision as a treatment for PJI after shoulder arthroplasty and assessed the reinfection rate on these patients, as well as other clinical outcomes, with a minimum follow-up of 12 months, were included. Study quality was evaluated using the MINORS score. Reinfection and complication rates were extracted and pooled estimates were calculated using the random-effect model. After careful screening, 44 studies were included, 5 reporting on one-stage, 30 on two-stage revisions and 9 assessing both strategies. There were 185 shoulders reported in one-stage revision studies, and 526 shoulders in two-stage. The overall pooled random-effects reinfection rate was 6.68% (95%CI: 3.76-10.13), with low heterogeneity (I2=28%, p=0.03). One-stage revision showed a reinfection rate of 1.14% (95%CI:0.00-4.88) and two-stage revision analysis revealed a reinfection rate of 8.81% (95%CI:4.96-13.33). There were significant statistical differences between one and two-stage reinfection rates (p=0.04). The overall pooled rate for other clinical complications was 16.76% (95%CI:9.49-25.15), with high heterogeneity (I2=70%, p<0.01). One-stage revision had a complication rate of 6.11% (95%CI:1.58-12.39) and the two-stage revision complication rate was 21.26% (95%CI:11.51-32.54). This difference was statistically significant (p=0.03). This is the first systematic review and meta-analysis showing significant statistical differences between one and two-stage surgical revision in infected shoulder arthroplasties. Provided the right conditions exist, one-stage revision shows better results in infection control, with lower clinical complications and possible better clinical outcomes.


The Forced Marriage of Minors: A Neglected Form of Child Abuse.
The forced marriage of minors is child abuse, consequently duties exist to stop them. Yet over 14 million forced marriages of minors occur annually in developing countries. The American Bar Association (ABA) concludes that the problem in the US is significant, widespread but largely ignored, and that few US laws protect minors from forced marriages. Although their best chance of rescue often involves visits to health care providers, US providers show little awareness of this growing problem. Strategies discussed to stop forced marriages include recommendations from the UN, the ABA, and the UK. The author anticipates and responds to criticisms that first, no duty to intervene exists without better laws and practice guidelines; and second, that such marriages are not child abuse in traditions where parental rights or familism allegedly justify them.


Adult day centers: everything you wanted to know but were afraid to ask!
Adult day services are a growing component of the wide spectrum of home and community-based care. However, up until now there has been only sketchy information about how many centers there are, what they do, whom they serve, and how they operate. This research brief presents findings from a new study by Partners in Caregiving: The Adult Day Services Program at the Wake Forest University School of Medicine, which provides the most comprehensive information to date about this important service. Understanding what centers do and whom they serve can be the start of a beautiful relationship.


A chromatin-mediated reversible drug-tolerant state in cancer cell subpopulations.
Accumulating evidence implicates heterogeneity within cancer cell populations in the response to stressful exposures, including drug treatments. While modeling the acute response to various anticancer agents in drug-sensitive human tumor cell lines, we consistently detected a small subpopulation of reversibly "drug-tolerant" cells. These cells demonstrate >100-fold reduced drug sensitivity and maintain viability via engagement of IGF-1 receptor signaling and an altered chromatin state that requires the histone demethylase RBP2/KDM5A/Jarid1A. This drug-tolerant phenotype is transiently acquired and relinquished at low frequency by individual cells within the population, implicating the dynamic regulation of phenotypic heterogeneity in drug tolerance. The drug-tolerant subpopulation can be selectively ablated by treatment with IGF-1 receptor inhibitors or chromatin-modifying agents, potentially yielding a therapeutic opportunity. Together, these findings suggest that cancer cell populations employ a dynamic survival strategy in which individual cells transiently assume a reversibly drug-tolerant state to protect the population from eradication by potentially lethal exposures.


N-Heterocyclic carbene stabilized Ag-P nanoclusters.
The N-heterocyclic carbene (NHC) 1,3-di-isopropylbenzimidazole-2-ylidene ((i)Pr2-bimy) is found to be an excellent ligand for the stabilization of silver-phosphorus polynuclear complexes. The straightforward preparation and characterization of the clusters [Ag12(PSiMe3)6((i)Pr2-bimy)6] (1) and [Ag26P2(PSiMe3)10((i)Pr2-bimy)8] (2) are described, representing the first examples of such structurally characterized, higher nuclearity complexes obtained using this class of ligands.


[Identification of Mycobacteriaceae species based on the hsp-65 gene polymorphism analysis by PCR - RFLP].
The polymorphism of the short fragment of the heat shock protein 65 encoding gene was evaluated by the PCR - RFLP technique described by Telenti and further developed by Devallois for identification of mycobacterial species in routine laboratory work. We analysed 58 strains representing 25 different mycobacterial species (24 reference strains and 34 clinical isolates). The results obtained by PCR-RFLP and HPLC identification techniques were highly concordant The results were compatible for 87,5% (21 / 24) reference strains and for 97,1% (33/34) clinical isolates. The PCR - RFLP method allowed for accurate identification mycobacterial species, especially pathogenic strains. Restriction patterns obtained for 25 species of Mycobacteriaceae genus could help in constructing the data base and algorithms used in routine laboratory practice.


Personalized medicine for glioblastoma: current challenges and future opportunities.
The failure to control glioblastoma progression is a major challenge for neuro-oncologists. Emerging data indicate that genetic and epigenetic heterogeneities within tumor cells play a dominant role in the development of resistant disease. These heterogeneities develop because driver mutations enable the proliferation of certain clones of transformed cells within the tumor microenvironment while pre-existing passenger or secondary mutations emerge from the clonal selection process during treatment. In addition, epigenetic changes provide another means of modifying the existing heterogeneous genetic background of tumor cells. These cumulative changes create challenges for the detection, characterization and treatment of glioblastomas, but new opportunities allow the development of advanced diagnostic modalities and individualized therapies. Furthermore, mutations in the epidermal growth factor receptor (EGFR) alter binding capability to targeted agents like erlotinib, rendering it inactive to block EGFR signaling. Receptor class switching and tyrosine kinase decoupling from cell cycle machineries are also mechanisms that can render tumor cells resistant to EGFR blockade. Therefore, effective therapy most likely requires the combination of personalized medicine treatment offered by targeted drugs and less specific therapies that aim at other processes within the tumor microenvironment. The goal is to take advantage of the specificity offered by targeted drugs to block proliferation of tumor cells harboring driver mutations while less specific treatments can be used against cells with passenger mutations.


[The essay on separation of dispensary from medical practice written by Yukichi Fukuzawa].
In November 1891, the union of pharmacists submitted the petitions letter on revision of the Law No. 10 issued on March 15, 1889, because by this law physicians acquired the right to dispense medicine rather than to give prescriptions to their patients. Yukichi Fukuzawa criticized the above mentioned problems and he contributed essays to the famous newspaper, Jiji-shin-pou in december 1891. Principles of his essays were as follows: 1) separation of dispensary from medical practice widely done in western countries were important from scientific viewpoint; 2) however, both physicians and patients had no concept on total medical fee which was consistent with consultation fee and charge for medicines. Thus, patients in Japan have been receiving medicines from physicians customarily over several hundred years; 3)introduction of new system on separation of dispensary from medical practice would cause troubles, because additional payment at the pharmacy should be required other than payment for physicians; 4)he was aware that opportunities to commit sick persons to doctor's care would be decreased especially in case of poor persons. Compared the public opinion to the separation of dispensary from medical practice of present day, there was found no difference on the attitude of Japanese people in these hundred years.


Double hexamer disruption and biochemical activities of Methanobacterium thermoautotrophicum MCM.
Methanobacterium thermoautotrophicum MCM (mtMCM) is a helicase required for DNA replication. Previous electron microscopy studies have shown mtMCM in several oligomeric forms. However, biochemical studies suggest that mtMCM is a dodecamer, likely a double hexamer (dHex). The crystal structure of the N-terminal fragment of mtMCM reveals a stable dHex architecture. To further confirm that the dHex is not an artifact of crystal packing of two hexamers, we investigated the relevance of the dHex by disrupting the hexamer-hexamer interactions seen in the crystal structure via site-directed mutagenesis and examining various biochemical activities of the mutants in vitro. Using a combination of biochemical and structural assays, we demonstrated that changing arginine to alanine at amino acid position 161 or the insertion of a six-aminoacid peptide at the hexamer-hexamer interface disrupted dHex formation and produced stable single hexamers (sHex). Furthermore, we showed that the sHex mutants retained wild-type level of ATPase and DNA binding activities but had decreased helicase activity when compared with the wild type dHex protein. These biochemical properties of mtMCM are reminiscent of those of SV40 large T antigen, suggesting that the dHex form of mtMCM may be the active helicase for DNA unwinding during the bidirectional DNA replication.


Gradients of HLA diversity in South American Indians.
Information concerning the HLA-A and -B loci was considered in relation to 3796 Amerindians living in 39 places in South America, data related to HLA-C being based on a smaller subset of 2989 persons distributed among 33 localities. Synthetic gene frequency maps were then constructed using principal-components analysis. Clearly significant longitudinal (principal component 1) and latitudinal (principal components 1, 2, and 3) clines were observed, most probably indicating ancient migration routes.


The Accuracy of Acetabular Cup Positioning Using Patient-Specific 3D Orientation Guidance in Total Hip Arthroplasty.
Malpositioning of the acetabular cup during total hip arthroplasty (THA) increases the risk of certain complications and shortens the lifespan of the prosthetic joint. Therefore, the accurate placement of the acetabular component during a THA is a necessary contributing factor to its successful outcome. The different methods of intraoperative estimation of acetabular component positioning are quite varied and sometimes may be inaccurate. The purpose of this study was to assess the accuracy of intraoperative acetabular component orientation with the assistance of three-dimensional (3D), patient-specific guidance alone. At a single institution, a total of 56 patients were prospectively enrolled into this study. Acetabular cup positioning was achieved with a described method using a laser beam technique minus the placement of pelvic pins. Comparison was made between the planned, preoperative inclination and version angles with the achieved postoperative inclination and version of the acetabular component in all THAs performed. The accuracy of placement of the acetabular cup was assessed using postoperative computed tomography (CT) scans. Evaluation was performed by an independent orthopaedic surgeon. Fifty-eight hips were included in the present study. The mean absolute deviation from the preoperative planned inclination and anteversion was 4.0° (0.1° to 14.6°; p<0.05) and 4.4° (0.2° to 12.2°; p<0.05) respectively. The planned inclination and anteversion were achieved within a +/- 10° target in 98% of the cases respectively. Accuracy of acetabular cup orientation in total hip arthroplasty can be achieved to a high degree with 3D patient-specific guidance alone. This eliminates the pins in the pelvis and has the potential to reduce costs and patient trauma without impacting accuracy.


Evaluation of indoor gamma radiation dose in dwellings.
The use of materials containing naturally occurring radionuclides for house construction may enhance the natural radiation background to which some population groups are exposed. External exposure results from gamma emitter radionuclides existing in the walls, floor and ceiling. Mathematical models can be used to predict external dose rates inside a room, provided the compartment geometry and the radionuclide concentration activities are known. This paper presents a methodology and a computer code for theoretical evaluation of indoor external gamma doses in the air. The room was modelled as three pairs of rectangular slabs of finite thickness. Doses were evaluated by applying a photon transport model, taking into account self-absorption and radiation build-up. Calculations were performed for 40K, 226Ra and 232Th, considering concrete walls. The results obtained show good agreement with those reported in the literature. Dose conversion factors are presented in a practical manner, ready to use for radiological impact screening.


Selective loss of podoplanin protein expression accompanies proteinuria and precedes alterations in podocyte morphology in a spontaneous proteinuric rat model.
To evaluate changes during the development of proteinuria, podocyte morphology and protein expression were evaluated in spontaneously proteinuric, Dahl salt-sensitive (Dahl SS) rats. Dahl SS rats on a low-salt diet were compared with spontaneously hypertensive rats (SHR) at age 2, 4, 6, 8, and 10 weeks. Blood pressure, urinary protein excretion, urinary albumin excretion, and podocyte morphology were evaluated. In addition, the expression of 11 podocyte-related proteins was determined by analyzing protein and mRNA levels. In Dahl SS rats, proteinuria became evident around week 5, increasing thereafter. SHR rats remained non-proteinuric. Dahl SS rats showed widespread foot process effacement at 10 weeks. At < or =8 weeks, expression and distribution of the podocyte proteins was similar between the two strains, except for the protein podoplanin. At 4 weeks, podoplanin began decreasing in the glomeruli of Dahl SS rats in a focal and segmental fashion. Podoplanin loss increased progressively and correlated with albuminuria (r = 0.8, P < 0.001). Double labeling experiments revealed increased expression of the podocyte stress marker desmin in glomerular areas where podoplanin was lost. Dahl SS rats did not show podoplanin gene mutations or decreased mRNA expression. Thus, podocyte morphology and the expression and distribution of most podocyte-specific proteins were normal in young Dahl SS rats, despite marked proteinuria. Our study suggests that decreased expression of podoplanin plays a role in the decrease of glomerular permselectivity.


Inferring Social Influence of Anti-Tobacco Mass Media Campaign.
Anti-tobacco mass media campaigns are designed to influence tobacco users. It has been proved that campaigns will produce users' changes in awareness, knowledge, and attitudes, and also produce meaningful behavior change of audience. Anti-smoking television advertising is the most important part in the campaign. Meanwhile, nowadays, successful online social networks are creating new media environment, however, little is known about the relation between social conversations and anti-tobacco campaigns. This paper aims to infer social influence of these campaigns, and the problem is formally referred to as the Social Influence inference of anti-Tobacco mass mEdia campaigns (Site) problem. To address the Site problem, a novel influence inference framework, TV advertising social influence estimation (Asie), is proposed based on our analysis of two real anti-tobacco campaigns. Asie divides audience attitudes toward TV ads into three distinct stages: 1) cognitive; 2) affective; and 3) conative. Audience online reactions at each of these three stages are depicted by Asie with specific probabilistic models based on the synergistic influences from both online social friends and offline TV ads. Extensive experiments demonstrate the effectiveness of Asie.


Hemostatic and fibrinolytic activation is less following cutting balloon angioplasty of the coronary arteries.
Recent studies have shown that percutaneous coronary intervention (PCI) activates systemic hemostatic activity, reflecting platelet activation and thrombin formation in the coronary arteries. The present study compared systemic levels of hemostatic markers induced by plain old balloon angioplasty (POBA), coronary stenting (STENT), and cutting balloon (CB) angioplasty. Sixty-one patients with stable angina pectoris, who underwent elective PCI or diagnostic coronary angiography (CAG) alone, were investigated. Patients who underwent PCI were divided into the POBA group (n = 11), the STENT group (n = 27), and the CB group (n = 11). Patients who underwent CAG alone were assigned to the CAG group (n = 12). Blood samples were collected before, 24 hours after, and 3 days after PCI or CAG. Plasma concentrations of prothrombin fragment 1+2 (F1+2), fibrinopeptide A (FPA), thrombin-antithrombin III complex (TAT), and plasminogen activator inhibitor-1 (PAI-1) were measured. In the CB group, the F1+2 (1.23 +/- 0.4 nmol/L) level 3 days after PCI was significantly smaller than that of the POBA group (2.37 +/- 0.5 nmol/L) (P < 0.05). The FPA (1.81 +/- 0.9 ng/mL), TAT (3.36 +/- 1.2 ng/mL) and PAI-1 (23.0 +/- 4.1 ng/mL) levels in the CB group 3 days after PCI were significantly smaller than those of the POBA group (P < 0.05, respectively) and STENT group (P < 0.05, respectively), but similar to the CAG group. Systemic hemostasis is activated to a greater extent after POBA and stenting than it is after CB angioplasty of the coronary arteries. This may contribute to the favorable long-term outcome of CB angioplasty.


A 19-nucleotide sequence upstream of the 5' major splice donor is part of the dimerization domain of human immunodeficiency virus 1 genomic RNA.
The genome of all retroviruses, including human immunodeficiency virus type 1 (HIV-1), consists of two identical RNAs noncovalently linked near their 5' end. Dimerization of genomic RNA is thought to modulate several steps in the retroviral life cycle, such as recombination, translation, and encapsidation. We report the results of experiments designed to identify the 5' and 3' boundaries of the dimerization domain of the HIV-1 genome: (1) An HIV-1 RNA starting at nucleotide 252 or at other downstream positions (four tested) does not dimerize despite the inclusion of the whole of a previously proposed dimerization domain (nucleotides 295-401); (2) an RNA starting between nucleotides 242 and 249 (five positions tested) dimerizes to a variable extent depending on the starting position; (3) an RNA starting at nucleotide 233 or at other upstream positions (five tested) is fully or > 80% dimeric; (4) an RNA starting at nucleotide 1 but lacking the 233-251 or the 242-251 region is, respectively, fully monomeric or about 50% monomeric; (5) the 343-401 region contains two strings of G's (GGGGG367 and GGG384) that had been postulated to promote genome dimerization through the formation of guanine quartets. We have deleted the 379-401, 358-401, and 343-401 regions from otherwise dimeric RNAs without changing their ability to dimerize. We reach three conclusions: (1) a dimerization signal exists upstream of the major 5' splice donor (nucleotide 290); (2) the previously proposed downstream dimerization domain is insufficient to promote dimerization and has a 3' half that is not necessary to obtain fully dimeric RNAs; (3) the 5' boundary of the HIV-1 dimerization domain is located somewhere between nucleotides 233 and 242, and the 3' boundary is located no farther than at nucleotide 342, making it possible that the 5' and 3' boundaries of the HIV-1 dimerization domain are both located within the leader sequence. We speculate that the 248-270 or 233-285 region forms a hairpin that is the core dimerization domain of HIV-1 RNA.


HIV counseling and testing: behavior and practices of women of childbearing age in Abidjan, Côte d'Ivoire. DYSCER-CI Group.
We assessed factors associated with women's attitudes toward HIV test results in gynecology clinics in Abidjan, Côte d'Ivoire. HIV testing was systematically offered to nonpregnant women attending two gynecology clinics in Abidjan. Individual pretest counseling was performed by trained midwives. Posttest counseling was given 2 weeks later to women who wished to know their HIV test results. HIV testing was offered to a total of 1482 women, of whom 1401 (94.5%) agreed to be screened. The prevalence of HIV infection was 21.3%. Of the women who participated, 10% failed to return. Youth, low educational level, and absence of genital infection were findings individually associated with failure by participants to return for their test results. Among the 1242 women who returned, 13.7% did not wish to know the results of their HIV test. A positive HIV test result, being native to Côte d'Ivoire, a high educational level, and knowing the existence of the asymptomatic stage of HIV infection were factors independently associated with declining to know the HIV test result. In conclusion, women who declined to know their HIV test results presented a specific profile at the time of HIV testing. This information can be used to improve pretest counseling and the efficacy of future HIV screening programs.